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Radiance Research AcademyInternational Journal of Current Research and Review2231-21960975-52411213EnglishN2020July6HealthcareMorphological and Morphometrical Analysis of First Rib: An Anthropological Study
English0105Nisha R PillaiEnglish Jyothi K CEnglish Shailaja ShettyEnglishIntroduction: The first rib is the most curved rib and very distinct from other ribs. The significant landmarks on the first rib include the head, tubercle, vascular groves on the superior surface and the scalene tubercle. Anomalous ribs are often discovered incidentally on chest radiographs. Such anomalies, maybe associated with the compression of the neurovascular bundle at the root of the neck. Further research on the first rib may also yield information that substantiates the growing relevance of first rib in sex identification and age estimation, particularly when the skull and pelvis are damaged to a significant extent.
Objectives: This study aims to analyze the morphological and morphometrical variations of first rib and understand the significance of such variations.
Materials and Methods: 35 right and 35 left first ribs were used for the purpose of this study. All the measurements were taken with digital Vernier calipers and flexible cloth tape. The findings were recorded and analyzed statistically. The study was conducted in Department of Anatomy, M. S. Ramaiah Medical College, Bengaluru.
Results: As far as the morphological parameters were concerned, scalene tubercles were either absent or rudimentary in nearly 50% of the ribs on both right and left sides. Similarly, vascular grooves were either absent or insignificant in approximately half of the ribs on both right and left sides. The variations of the head and the tubercle of the first rib were not encountered frequently.
Conclusion: Malformations of the first rib are common. When present, it may lead to compression of neurovascular bundle at the root of the neck causing thoracic outlet syndrome. Awareness of such anomalies are important for anatomists, radiologists and thoracic surgeons dealing with this region.
EnglishFirst rib, Angle of rib, Scalene tubercle, Malformation, Thoracic outlet syndromeINTRODUCTION
The thoracic wall is made up of sternum anteriorly, twelve thoracic vertebrae and their intervertebral disc posteriorly and twelve pairs of ribs and their costal margins laterally. The first rib is the most curved and frequently the shortest1.It forms the boundary for the thoracic inlet. The scalenus anterior is inserted into the inner border of the first rib, producing the scalene tubercle. Independent studies by Wattanasirichaigoon and Castriota suggested that rib anomalies are common, with approximately 2% in the general population. It is of paramount importance for radiologists to be able to identify these, so as to avoid misinterpretation of radiographs2. Most familiar rib anomalies include cervical rib, bifid rib, rib dysplasia.
The dimensions of the ribs are recognized to have a bearing on the development of thoracic outlet syndrome3,4.
The first rib is gradually gaining importance and being ratified for estimation of the age of young adult skeletons5.The use of first rib for sex identification is also being explored under the domains of Forensic Anthropology. Its importance is further amplified by the fact that it is less liable to be damaged as against other skeletal remains6.
Measurements of ribs have also been employed in biomechanical formulae for respiration, truncal structure and identifying lateral asymmetry in diagnosis of scoliosis7.
The present study aims to analyze the morphological and morphometrical variations of the first rib and understand its significance.
MATERIAL AND METHODS
70 first ribs (35 right and 35 left first ribs) were procured from the Department of Anatomy, M S Ramaiah Medical College.
Inclusion criteria- All intact right and left ribs were included.
Exclusion criteria- Damaged first ribs.
Morphological Study: Variations regarding the scalene tubercle, vascular grooves, head and tubercle of the rib were recorded carefully and expounded.
Actual Internal Length (A1): measured along the inner curvature of the first rib from the posterior sternal end to the medial side of the head of the rib.
Actual External Length (B1): measured along the outer and greater curvature of the first rib from the anterior sternal end to the lateral side of the head of the rib. ( Fig 1)
Both A1 and B1 were measured with the aid of a flexible cloth tape and recorded in centimeters.
Shortest Internal Length (A2): Measured from the posterior sternal end to the medial side of the head of the rib.
Shortest External Length (B2): Measured from the anterior sternal end to the lateral side of the head of the rib. ( Fig 2)
Both A2 and B2 were measured using a digital Vernier caliper and recorded in centimeters.
Angle of the first rib: The rib was placed on an even flat surface in the non-anatomical position as shown in figure 1. Inverse sine function in Microsoft Excel was used to determine the angle formed between the neck of the rib and the flat surface on which it was placed. ( Fig 3)
Statistical Analysis:
All the qualitative variables like the incidence of anomalies of the first rib will be presented using frequency and percentage. All quantitative variables like will be analyzed using descriptive statistics such as mean and standard deviation. Comparison between the right and left side values will be carried out using student’s ' t 'test.
RESULTS
In this study, 35 right-sided and 35 left-sided first ribs were analyzed for their morphology and morphometry. All the morphometric parameters were found to be higher for the right ribs than those on the left, however it was not statistically significant.
The mean and the standard deviation of the angle on the right side was 15.82° ± 6.97, the maximum angle recorded being 28.42º and minimum being 0º. On the left side, the mean and standard deviation was 14.76° ± 4.89, the maximum being 26.74º and minimum being 8.53º.
Absent or insignificant vascular grooves were noted in nearly 50% of the ribs. Variations of the head and tubercle were not very common. Variations of the head and tubercle were not very common. 97.1% of the right ribs and 91.4% of the left ribs did not have a rudimentary head or tubercle. Only 2.9% ribs on either side showed rudimentary head and tubercle. Rudimentary or absent scalene tubercle were observed in about 50% of the ribs. (Fig 4,5)
The results are tabulated (Table 1- 5)
DISCUSSION
First rib studies have been conducted on radiological grounds as well as by inspection of dry bones. A study on rib anomalies by Etter encompasses a comprehensive radiological assessment of 40,000 cases, the main inference from it being that the most frequently encountered anomaly in the course of the study was forked rib8.
Another study evaluated the accuracy of CT derived first rib measurements for the determination of sex9.
In a study conducted by Sunita Bharati et al, with a sample size of 48 first ribs, 18.75% of the ribs did not have a Scalene tubercle and 18.75% of the ribs did not have vascular grooves. The mean values for the Actual External Length (B1) on right and left side were found to be 7.63cm and 7.86cm respectively10.
Rashia et al. studied 50 first ribs, and reported absent scalene tubercles in 46% of the ribs. As per the study, 28% of the ribs did not have vascular grooves, while rudimentary tubercle and head were found in 12% and 5.7% of the ribs respectively11.
D Souza et al. conducted a study to assess the adequacy of the first rib in identification of the sex. The mean of the Actual External Length (B1) on the right side was estimated to be 12.13cm, while the mean for the same on the left side was12.19cm. The mean of the angle of the rib on the right and left sides were 13.5 and 15.1° respectively12.
In our study, we found that 22.5% of the ribs lacked a scalene tubercle and 50% of the ribs did not have vascular grooves. Rudimentary tubercle and head was reported in 24% and 2.85% of the ribs respectively. The mean values of B1 were found to be 12.97cm and 12.81cm on the right and left side respectively. The lack of coherence with the study conducted by Sunita et al. maybe attributed to racial differences.
A study conducted by Elrod suggests that sex of the individual maybe determined by using the angle of the first rib alone with a probability of 60.2%. The probability is enhanced to 70.5% if the angle of the first rib and its total length is taken into consideration13.
Similarly, another study which analyzed the utility of the first rib in sexing individuals stated that a combination of metric and geometric morphometric variables could yield a correct sex classification in European Americans and African Americans as high as 88.05% and 70.86% of the times respectively, thereby highlighting the role of ancestry and race in determining the characteristics of the rib14.
CONCLUSION
From the above comparisons, it can be inferred that the morphometric parameters are not significantly different; however the morphological parameters show wide variations.
The racial and the regional factors are likely to have a bearing on the morphological features of the ribs. Further research conducted in this light may help establish a more concrete association between race and rib characteristics.
The differences in the right and left values of the morphometric parameters is a chance occurrence as evidenced by the p-values obtained from the paired t-test.
Acknowledgements:
Authors acknowledge the immense help received from Mrs Radhika our statistician for the statistical analysis. Authors acknowledge the immense help received from the scholars whose articles are cited and included in references of this manuscript. The authors are also grateful to authors/ editors/ publishers of all those articles, journals and books from where the literature for this article has been reviewed and discussed.
SOURCE OF FUNDING: N/A
CONFLICT OF INTEREST: Nil
Englishhttp://ijcrr.com/abstract.php?article_id=2695http://ijcrr.com/article_html.php?did=26951. S Standring, Ed., Gray’s Anatomy: The Anatomical Basis of Clinical Practice, Churchill Livingstone-Elsevier, Philadelphia, Pa, USA, 41st edition, 2016. 936p.
2. Aign?toaei AM, Moldoveanu CE, C?runtu ID, Giu?c? SE, Vicoleanu SP, Nedelcu AH. Incidental imaging findings of congenital rib abnormalities- a case series and review of developmental concepts. Folia Morphologica 2018;77(2)386-392.
3. Chang CS, Chuang DC, Chin SC, Chang CJ. An investigation of the relationship between thoracic outlet syndrome and the dimensions of the first rib and clavicle. J Plast Reconstr Aesthet Surg 2011;64(8):1000-1006.
4. Weber AE, Criado E. Relevance of bone anomalies in patients with thoracic outlet syndrome. Ann Vasc Surg 2014;28(4):924-932.
5. Rios L, Cardoso HF. Age estimation from stages of union of vertebral emphyses of the ribs. Am J Phys Anthropol 2009;140(2):265-274.
6. Kurki H. Use of First Rib for Adult Age Estimation: A Test of One Method. International Journal of Osteoarchaeology2005;15:342-50.
7. WhiteT.D, Black M.T, Folkens P.A. Human Osteology. 3rd Edition.London: Elsevier 2012. 157p.
8. Etter LE. Osseous abnormalities in thoracic cage seen in forty thousand consecutive chest photoroentgenograms. AMJ Roentgenol. Radium Ther1994;51:359-363.
9. Kubicka AM, Piontek J. Sex estimation from measurements of the first rib in a contemporary Polish population. International Journal of Legal Medicine 2016;130(1):265-272.
10. Bharati S, Jothi S S. Morphometric and Morphological Study of First Rib. International Journal of Biomedical Research 2017;8(1):49-50.
11. Rashia S, Zaidi SHH. A morphological study of First Rib Anomalies. International Journal of Advanced & Integrated Medical Sciences 2017;2(2):70-72.
12. D Souza A, Hosapatna M, Ankolekar VH, D Souza AS. The Angle of the First Rib and its Implication in Forensic Anthropology: A Morphometric Study. Journal of Medical and Health Sciences 2014;58(2):189-191.
13. Elrod PW. The potential of the angle of the first rib, head to tubercle, in sexing adult individuals in forensic contexts 2012. LSU Master’s Theses. 3714.
14. Lynch JJ, Cross P, Heaton V. Sexual Dimorphism of the First Rib: A Comparative Approach Using Metric and Geometric Morphometric Analyses. Journal of Forensic Sciences 2017;62(5):1251-1258.
Radiance Research AcademyInternational Journal of Current Research and Review2231-21960975-52411213EnglishN2020July6HealthcareInfluence of Basic Fibroblast Growth Factor on Biological and Phenotypic Properties of Human Bone Marrow Mesenchymal Stem Cells
English0612Narendra NitilapuraEnglish Shama RaoEnglish Siddharth M. ShettyEnglish Meenakshi ArumugamEnglish Veena Shetty A.English Mohana Kumar B.EnglishBackground: Bone marrow-derived mesenchymal stem cells (BMSCs) are ideal candidates for cell-based therapy due to their self-renewal and multilineage differentiation ability. During in vitro expansion, BMSCs tend to lose their proliferation rate and multipotency limiting their clinical use. Hence, supplementation of basic fibroblast growth factor (bFGF) during in vitro culture might positively influence the biological and phenotypic properties of expanded BMSCs.
Aim: This study was aimed to evaluate the supplementation of bFGF on selected biological and phenotypic characteristics of BMSCs.
Methods: Plastic-adherent BMSCs were cultured without (0 ng/mL) and with (5 ng/mL and 10 ng/mL) bFGF up to five passages and analyzed for their morphology, viability, proliferation rate, population doubling time (PDT), colony forming unit-fibroblast (CFU-F) assay, senescence activity, genetic stability and cell surface marker expression.
Results: BMSCSs exhibited a small, spindle-shape morphology in bFGF supplemented groups as compared to elongated fibroblast-like cells in control. No significant difference in viability and PDT was observed. However, noticeable differences were observed in proliferation rate and CFU-F ability between bFGF supplemented group and control. Further, the senescence activity of BMSCs was considerably decreased under the influence of bFGF. BMSCs had a normal karyotypein both bFGF supplemented and control groups. Lastly, addition of bFGF in expansion media slightly modified the phenotypic markers expression in BMSCs, corresponding to the concentrations used.
Conclusion: Supplementation of BFGFat10 ng/mL could be considered as an optimal and efficient concentration for expanding BMSCs in culture before their use in cell-based therapy.
EnglishBasic fibroblast growth factor, Bone marrow mesenchymal stem cells, Human, In vitro, Markers expressionINTRODUCTION
Bone marrow is considered as the most commonly used tissue source of mesenchymal stem cells (MSCs)1. MSCs derived from bone marrow (BMSCs) are ideal candidates for cell therapy due to their ability of self-renewal and multilineage differentiation2. It is known that, occurrence of MSCs in the bone marrow is in low amount (0.001-0.01%), and ex vivo expansion is indispensable to obtain sufficient cell number for clinical applications and tissue engineering purposes3. It is observed that for cartilage tissue engineering, 8-10×107 cells/mL of tissue are needed initially4, and based on different nature of defects, a large number of cells are required for cell therapy purposes5. However, prolonged in vitro culture expansion of MSCs reduces proliferation potential and multipotency, and further leading to senescence which is undesirable for cell therapy6.Strategies such as modification of media composition, cell culture conditions, and the use of growth factors to enhance the proliferation of MSCs have been proposed to minimize the detrimental features.
Among the growth factors being employed, basic fibroblast growth factor (bFGF) has been shown to be involved in the promotion of self-renewal ability, maintenance of stemness, and suppression of senescence in vitroin MSCs derived from different tissue sources7-9. The supplementation of bFGF in culture medium enhanced the proliferation of BMSCs and periodontal ligament stem cells, and preservedtheir differentiation ability10-12.In addition, BMSCs grown under the influence of bFGF have displayed to maintain their stem cell features with enhanced proliferation rate and a greater propensity towards osteogenesis and chondrogenesis5, 13-14.
To further understand the influence of bFGF on BMSCs for cell-based therapeutic applications, we investigated its supplementation at 0, 5 and 10 ng/mL on selected biological and phenotypic characteristics, such as morphology, viability, proliferation rate and doubling time, colony-forming unit-fibroblast (CFU-F) ability, genetic stability, senescence activity and cell-surface markers expression. The results might offer additional support to the prospective utility of ex vivo expanded BMSCs supplemented with bFGF for cartilage tissue regeneration.
MATERIALS AND METHODS
Isolation and culture of BMSCs
Bone marrow sample collection and in-vitro procedures were approved by the Institutional Ethics Committee and Institutional Committee for Stem Cell Research (IC-SCR). Human bone marrow aspirates were collected and processed after obtaining informed consent from patients (n=3), who were undergoing knee arthroscopy procedure for ligament injury with cartilage damage. Under local anaesthesia, about 15-20 mL of bone marrow suspension was harvested from the posterior iliac crest and collected in a 50 mL tube containing the same volume of heparinized (10 U/mL) phosphate-buffered saline (PBS, Gibco, Life Technologies, Grand Island, NY, USA).
The establishment of cell cultures was performed by following previously published protocol with minor modifications15. Briefly, mononuclear cells from bone marrow aspirate were collected by density gradient solution (Ficoll-Paque PLUS; 1.077 g/mL, GE Healthcare Life Sciences, Uppsala, Sweden). The cells were washed twice in PBS and culturedin Dulbecco’s modified Eagle’s medium (DMEM, Gibco, Life Technologies) with 10% fetal bovine serum (FBS, Gibco, Life Technologies), 100 U/mL penicillin, and 100 μg/mL streptomycin (Gibco, Life Technologies) at 37°C in a humidified atmosphere and 5% CO2 in air.For culturing the adherent cells, the basal medium consisting of DMEM, 10% FBS, 100 U/mL penicillin, and 100 μg/mL streptomycin without (Control) or with bFGF (5 ng/mL and 10 ng/mL, Biolegend, CA, USA) was changed twice a week until the cells reached 80-90% confluency.Once reached confluency, all BMSCs were dissociated using a 0.25% (w/v) trypsin-ethylene-diaminetetraacetic acid (EDTA)(Gibco, Life Technologies) and sub-passaged five times for subsequent analyses.
Morphology
The morphology of BMSCs was assessed using phase-contrast microscope (Olympus, Tokyo, Japan) and any changes in morphological features during different time points of culture and also at various passages were recorded.
Viability assay
Cell viability was performed by 0.4% trypan blue (Gibco, Life Technologies) exclusion assay with a hemocytometer. The viability was assessed at every sub-passage of BMSCs.
Proliferation rate and population doubling time (PDT)
BMSCswere plated at 2×103 cells/cm2 in 12-well plates in a basal medium and cultured for 12 days. The culture medium was refreshed every 3 days. Cells in every three wells were detached with 0.25% trypsin-EDTA on day 3, 6, 9 and 12, and counted using a hemocytometer. The average cell numbers for every three wells in every replicate were determined and the proliferation rate was calculated. PDT was calculated using a formula; PDT= t(log2) / (log Nt-log No), where t represents culture time, and No indicate the cell numbers before seeding and Ntrepresent the cell numbers after seeding.
Colony-forming unit-fibroblast (CFU-F) ability
CFU-F ability of BMSCs was determined by seeding at a cell density of 0.5×103cells per well in 6-well culture plate, and cultured for 2 weeks with regular change of a fresh medium at every 3 days intervals. The cells were subsequently fixed in ice-cold ethanol for 5 min and the assay was performed using Crystal violet (Sigma-Aldrich, St. Louis, MO, USA) staining. All stained colonies which were made up of more than 25 cells were recorded as CFUs.
Senescence activity
The senescence activity in BMSCs was analyzed using senescence associated (SA)-β-Gal staining kit (Cell Signaling Technology, MA, USA) by following the manufacturers’ instructions. Briefly, the cells were washed with PBS and incubated for 15 min with 3.7% formaldehyde (Sigma-Aldrich), and again washed twice with PBS. Color development was observed by incubating the cells for overnight at 37°C with the kit-supplied staining solution (40mM citric acid/sodium phosphate pH 6.0, 150 mMNaCl, 2 mM MgCl2, 5 nM potassium ferricyanide, and 1 mg/ml X-gal in dimethyl sulphoxide). Cell culture plates were then observed for the development of blue colour by microscopic examination.
Karyotype analysis
Genetic stability was assessed by GTG-banded karyotype on metaphase spreads from cultured BMSCs at passage 4. GTG banding was carried out using trypsin (0.05%) and 1% Giemsa stain. Well banded metaphase spreads were analyzed using a fluorescence microscope (Olympus, Tokyo, Japan).
Phenotypic marker analysis by flow cytometry
Standard flow cytometry analysis was employed for determining the cell surface marker profile of BMSCs. Cells were analyzed for the expression of MSC-specific markers (CD29, CD73, and CD90) and the absence of CD34 and CD45 markers using Fluorescence-Activated Cell Sorter (FACSCalibur, Becton Dickinson, NJ, USA). Briefly, BMSCs at ~80% confluence were washed twice in PBS and incubated with 0.1% bovine serum albumin (Sigma-Aldrich) for 30 min to block nonspecific binding. Then, the cells were incubated with unconjugated anti-human mouse antibodies, such asCD29 (eBioscience, CA, USA, 1:100), CD73 (Biolegend, 1:100), CD90 (eBioscience, 1:100), CD34 (Biolegend, 1:100) and CD45 (eBioscience, 1:100) for 2 hrs at 37°C. Cells were washed twice in cell staining buffer (Biolegend), and incubated with fluorescein isothiocyanate (FITC)-conjugated anti-mouse IgG (eBioscience, 1:100) for 1 hr at room temperature. A minimum of 10,000 FITC-labeled cells were acquired (Forward scatter/Side scatter)and analyzed with Cell Quest software (Becton Dickinson). The corresponding isotype-matched (negative) control (eBioscience) was also used. The experiment was performed in duplicates and average data were obtained.
Statistical analysis
All data were expressed as the mean ± SD from at least three independent experiments. SPSS software (SPSS Inc, Chicago, USA) was used for one way analysis of variance (ANOVA) with Tukey’s post-hoc test. P values less than 0.05 were considered significant.
RESULTS
Primary culture establishment and morphology
MSCs were successfully isolated from low-density mononuclear cell population of bone marrow based on their selective attachment to plastic culture dishes when compared to hematopoietic cells. BMSCs at primary culture in basal medium were supplemented with bFGF (5 and 10ng/mL) in comparison to control (0 ng/mL). Readily adhered BMSCs reached 80-90% confluency in 15 days and used for analyses until passage 5.
BMSCs showed slightly elongated and fibroblast-like morphology in control (0 ng/ml bFGF, Figure 1A). Whereas in bFGF supplemented groups, cells showed small, spindle-shaped morphology (5ng/mL bFGF, Figure 1B and 10 ng/mL bFGF, Figure 1C). BMSCs supplemented with 10ng/mL bFGF exhibited more homogeneous and denser cell population than 5 ng/mL bFGF, despite exhibiting similar morphological features.
Viability, proliferation rate and PDT
Viability of BMSCs from all the groups at different passages was determined and any changes in viability during culture expansion were also recorded. No significant differences in percentage viability between control and bFGF supplemented BMSCs were observed. Cell viability was found more than 95% in all the three groups (Figure 2A). The proliferation of BMSCs in the initial days of culture (Day 0 to Day 3) was comparatively slow but increased remarkably from Day 6 to Day 12 (Figure 2B). A significant(p=0.001)difference was observed in terms of proliferation rate between 10 ng/mL bFGF and control BMSCs, whereas no significant (p=0.08)difference was found between 5 ng/mL bFGF and control. Moreover, no significant (p=0.17) difference in PDT was observed among all BMSCs, although PDT was slightly lower in 10 ng/mL bFGF supplemented group (Figure 2C).
Colony forming unit-fibroblast (CFU-F) ability
CFU-F ability of BMSCs between control and bFGF supplemented groups were determined at passage 3. Crystal violet stained colonies were recorded in 6-well culture plates with an initial seeding density of 0.5×103 cells/well.CFU-F assay was performed on 14th day of culture, and a higher number of colonies (more than 25 cells) was visualized in bFGF supplemented groups (both in 5 ng/mL bFGF and 10 ng/mL bFGF) than in control (Figure 3A-C).
Senescence associated β-galactosidase (SA-β-Gal) staining
BMSCs at passage 5 were subjected for senescence activity by SA-β-Gal assay and the results were recorded microscopically. BMSCs cultures showed a significantly lower number of senescent cells in bFGF supplemented groups when compared to control (Figure 4). However, no significant (p=0.10) difference was observed between 5ng/mL and 10 ng/mL bFGF supplemented BMSCs.
Karyotyping
Genetic stability of BMSCs was analyzed by GTG-banding. BMSCs from control and bFGF supplemented groups showed normal karyotype without any chromosomal aberrations (Figure 5).
Phenotypic marker analysis
BMSCs were phenotypically characterized by flow cytometry analysis with a panel of five markers at passage 3 after culture with or without bFGF. Flow cytometry analysis showed that the BMSCs from all the groups had a positive expression of MSC-specific markers, such as CD29, CD73 and CD90 in contrast to hematopoietic cells markers, CD34 and CD45, which showedEnglishhttp://ijcrr.com/abstract.php?article_id=2696http://ijcrr.com/article_html.php?did=2696
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Solchaga LA, Tognana E, Penick K, Baskaran H., Goldberg VM, Caplan AI, et al. A rapid seeding technique for the assembly of large cell/scaffold composite constructs. Tissue Eng 2006; 12:1851.
Solchaga LA, Penick K, Goldberg VM, Caplan AI, Welter JF. Fibroblast growth factor-2 enhances proliferation and delays loss of chondrogenic potential in human adult bone-marrow-derived mesenchymal stem cells. Tissue Eng Part A2010;16:3:1009-19.
Behrens A, Van Deursen JM, Rudolph KL, Schumacher B. Impact of genomic damage and ageing on stem cell function. Nat Cell Biol 2014; 16:201–207.
Nawrocka D, Kornicka K, Szydlarska J, Marycz K. Basic fibroblast growth factor inhibits apoptosis and promotes proliferation of adipose-derived mesenchymal stromal cells isolated from patients with type 2 diabetes by reducing cellular oxidative stress.Oxid Med Cell Longev 2017; 2017: 3027109.
Ito T, Sawada R, Fujiwara Y, Seyama Y, Tsuchiya T. FGF-2 suppresses cellular senescence of human mesenchymal stem cells by down-regulation of TGF-β2. BiochemBiophys Res Commun 2007; 359:108-14.
Wang R, Liu W, Du M, Yang C, Li X, Yang P. The differential effect of basic fibroblast growth factor and stromal cell-derived factor-1 pretreatment on bone morrow mesenchymal stem cells osteogenic differentiation potency. Mol Med Rep 2018 Mar; 17(3):3715-3721.
Tasso R, Gaetani M, Molino E, Cattaneo A, Monticone M, Bachi A, et al. The role of bFGF on the ability of MSC to activate endogenous regenerative mechanisms in an ectopic bone formation model. Biomaterials 2012; 33(7):2086–96.
Zhang C, Guo H, Yang, Chen, Huang, Liu, et al. The biological behaviour optimization of human periodontal ligament stem cells via preconditioning by the combined application of fibroblast growth factor-2 and A83-01 in in vitro culture expansion. J Transl Med 2019; 28:17(1):66.
Solchaga LA, Penick K, Porter JD, Goldberg VM, Caplan AI, Welter JF. FGF-2 enhances the mitotic and chondrogenic potentials of human adult bone marrow-derived mesenchymal stem cells. J. Cell. Physiol 2005; 203(2):398-409.
Song, G, Ju Y, Soyama H. Growth and proliferation of bone marrow mesenchymal stem cells affected by type I collagen, fibronectin and bFGF.MaterSciEng C2008; 1467–1471.
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Park BW, Kang EJ, Byun JH, Son GM, Kim JH, Hah YS, et al. In vitro and in vivo osteogenesis of human mesenchymal stem cells derived from skin, bone marrow and dental follicle tissues. Differentiation 2012; 83(5):249?259.
Vellasamy S, Vidyadaran S, George E, Ramasamy R. Basic fibroblast growth factor enhances the expansion and secretory profile of human placenta-derived mesenchymal stem cells. Malaysian J Med Health Sci 2016; 12: 49-59.
Tae JY, Ko Y, Park JB. Evaluation of fibroblast growth factor-2 on the proliferation of osteogenic potential and protein expression of stem cell spheroids composed of stem cells derived from bone marrow. Exp Ther Med 2019; 18(1):326-331.
Zeng S, Fang Y, Zhang Q, Peng B, Zhang Z, Zhao W, et al. Effect of basic fibroblast growth factor on the gingiva-derived mesenchymal stem cells.Int J Clin Exp Med 2019; 12(5):6347-6356.
Karlsen TA, Brinchmann JE. Expression of inflammatory cytokines in mesenchymal stromal cells is sensitive to culture conditions and simple cell manipulations. Exp Cell Res 2019; 1; 374(1):122-127.
Wu J, Huang GT, He W, Wang P, Tong Z, Jia Q, et al. Basic fibroblast growth factor enhances stemness of human stem cells from the apical papilla.J Endod 2012; 38(5):614-22.
Park J, Lee J, Yoon BS, Jun KE, Lee G, Kim YI, et al. Additive effect of bFGF and selenium on expansion and paracrine action of human amniotic fluid-derived mesenchymal stem cells. Stem Cell Res Ther 2018; 9:293.
Nekanti U, Mohanty L, Venugopal P, Balasubramanian S, Totey S, Ta M. Optimization and scale-up of Wharton’s jelly-derived mesenchymal stem cells for clinical applications. Stem Cell Res 2010; 5(3):244-54.
Radiance Research AcademyInternational Journal of Current Research and Review2231-21960975-52411213EnglishN2020July6HealthcareCardiac and pulmonary late effects in Hodgkin’s lymphoma survivors in The Republic of North Macedonia
English1318Gazmend AmzaiEnglish Milce CvetanoskiEnglish Oliver KaranfilskiEnglish Sonja Genadieva StavricEnglish Aleksandar StojanovicEnglishBackground: Survivors with HL express higher morbidity and mortality rates than the general population of comparable age, mainly because of the late cardiological and pulmonary complications associated with the duration and character of previously administered therapy. The objectives of this study are to determine changes in cardiac and pulmonary functions in patients with Hodgkin’s lymphoma treated with chemotherapy with or without mediastinal radiation therapy.
Patients and Methods: The study includes 287 patients with Hodgkin's lymphoma. An analysis of the ECG, echocardiography and spirometric examinations were utilized for the detection of potential cardiac and pulmonary late complications, resulting from the treatment of patients, following long-term remissions.
Results: Late adverse effects are a factor that further increases morbidity and mortality in our surviving HL patients. In 20.8% of the patients, heart disease was detected. It is confirmed that the total dose of doxorubicin influences the onset of late cardiac complications with statistical significance. Late cardiac adverse events occurred in 17.3% of our patients, who received a cumulative dose of doxorubicin greater than 200 mg/sq.m. Patients who received additional mediastinal radiotherapy, had an incidence of heart disease twice higher than patients who received chemotherapy only. In our analyzed series of patients, 24.7% manifested pulmonary toxicity and in 12.7%, a severe degree of pulmonary ventilatory failure was detected. With regard to the latter findings, we also confirm that patients who are receiving bleomycin develop significantly more pulmonary disorders, compared with patients who are receiving chemotherapy regimens without bleomycin.
Conclusion: Improvements have been introduced in formulating certain drugs, so that cardiotoxic effects are reduced or with diminished intensity, or even completely omitting them and replacing them with a less or non-toxic drug. With regard to radiotherapy, size and shape of radiation fields can be precisely customized and dose reduction became acceptable. Despite the progress achieved regarding treatment outcomes in HL patients, due to the optimization of therapeutic protocols, the issue of potential side effects, arising as a treatment consequence, remains a concern.
EnglishHodgkin’s lymphoma, Late complications, Cardiac complications, Pulmonary complicationsIntroduction
HL is very sensitive to chemotherapy and radiation, but treatment-related toxicity raises serious concerns and has a negative impact on the quality of life and the long term overall survival1. Late complications due to toxicity attributable to therapy are a major cause of late morbidity and mortality. Survival is expected to be long enough for patients to carry a lifetime risk of late treatment-related complications. Generally, more serious late complications of treatment are secondary malignancies, cardiac, pulmonary complications and infertility2-5.
A major challenge today is the reduction in mortality from cardio-pulmonary complications arising following treatment. The goal of high quality care is to minimize the adverse effects of treatment, while simultaneously maximizing the disease cure rate.
Many published reports and many relevant studies analyzing large groups of patients, have proven that the toxicity of otherwise successful treatment options ranks cardiovascular disorders as the most common non-malignant cause of death in these long-term survivor patients with Hodgkin's lymphoma.
Patients with Hodgkin's lymphoma, whose overall survival is longer than 5 years, have a 3 to 5 times higher incidence of several cardiovascular disorders, compared to the general population. The 25-year cumulative incidence of heart disease is 7.9% after combined chemotherapy and radiotherapy6.
Anthracyclines are one of the most widely prescribed, as well as among the most effective anticancer agents for the treatment of multiple solid tumors and hematological malignancies. Doxorubicin, as a chemotherapeutic, belongs to the family of anthracycline-type drugs and is a key component of chemotherapy regimens used in the treatment of Hodgkin's lymphoma. Although it is the most active substance and an essential component in the treatment of Hodgkin's lymphoma, unfortunately, life-threatening (lethal) cardiotoxicity continues to compromise its overall value. Despite many years of research, the exact mechanism of cardiotoxicity has not been fully elucidated. It is widely considered that doxorubicin is binding to iron, forming an intracellular complex, which catalyzes the production of highly reactive radicals that cause oxidative damage to myocytes.
The cardiotoxicity of doxorubicin is exponentially proportional to the dose administered. Heart failure will develop in approximately 30% of patients who receive a cumulative dose higher than 550 mg/sq.m. doxorubicin, and only in 4% of patients who receive a lower cumulative dose7-9. Cumulative doses of doxorubicin in the two most widely used chemotherapy regimens for Hodgkin's lymphoma, over 6 cycles of ABVD and 6 cycles of escalated BEACOPP regimen are 300 mg/sq.m. and 210 mg/sq.m. However, there is no safe dose for doxorubicin, because asymptomatic ventricular damage may occur even in patients receiving lower doses of doxorubicin, as a result of myocyte loss and interstitial fibrosis. This is confirmed by a study in which endomyocardial biopsy revealed typical histopathological changes at doses of doxorubicin 14 years, documented histopathological diagnosis i.e., initial diagnosis of Hodgkin’s lymphoma, valid medical documentation with clinical and laboratory data on the primary disease, administered therapy as well as the clinical follow-up data of the patient. Patients who experienced long-term remissions underwent the following procedures:
ECG and echocardiography are the most widely non-invasive methods used for cardiac evaluation and assessment of anthracycline-induced cardiotoxicity.
Spirometry for functional lung assessment.
Cardiologists and pulmologists analyzed echocardiograms and spirograms. All patients had cardiac and pulmonary evaluation prior to the start of chemotherapy and showed no sign of disease. Patients who had active heart or lung disease were excluded from the study prior to treatment. Assessment, toxicity analysis, distribution of late types of complications and non-neoplastic complications (cardiac, pulmonary complications), following both chemotherapy and radiotherapy, which became notable in our patient population during the follow-up and observation period, were the points of interest of this study. Data was compared with relevant literature reports, in order to assess the rate of complications in our population, versus data reported in respectable journals.
The statistical program SPSS 17.0 was used for performing general and specific statistical analyses. Databases were created in standard and generally available software programs. Standard descriptive and analytical methods were used for data presentation and preparation for analyses. The Shapiro-Wilk`s test was used for determination of statistical significance for p less than 0.05. The results are presented in tables and graphics.
Results
Post-therapy echocardiography, ECG and cardiac examination were performed in 168 patients with HL. In 79.2%, or 133 patients, a regular cardiac finding was recorded and in 20.8%, or 35 patients, a cardiac disorder was detected, mainly cardiomyopathy (40%), shown in Table 1.
In principle, we have monitored the effect of radiation and assessed the long-term cardiac adverse effects. There is a definite relationship between the treatment modality, respectively patients receiving chemotherapy alone and patients receiving combined therapy (chemo + radiotherapy) and the echocardiographic abnormalities, delineating the more intensely treated population as the one at higher risk, manifesting significant statistical difference with a p-value 200 mg/sq.m. and 6 patients received a total dose of doxorubicin ≤200 mg/sq.m., the percentage difference being statistically significant with a p value Englishhttp://ijcrr.com/abstract.php?article_id=2697http://ijcrr.com/article_html.php?did=2697
Andrea K Ng. Current survivorship recommendations for patients with Hodgkin lymphoma: Focus on late effects. Blood. 2014 Nov;124(23):3373–79.
Hodgson D. Late Effects in Era of Modern Therapy for Hodgkin Lymphoma. Hematology Am Soc Hematol Educ Program. 2011 Dec;2011(1):323-9.
Master M, et al. Late Morbidity and Mortality in Patients With Hodgkin’s Lymphoma Treated During Adulthood. J Natl Cancer Inst. 2015 Feb;107(4).
Bessell EM, et al. Long-term survival after treatment for Hodgkin’s disease (1973-2002): improved survival with successive 10-year cohorts. Br J Cancer. 2012 Jul;107(3):531-6.
Castellino SM, et al. Morbidity and mortality in long-term survivors of Hodgkin lymphoma: a report from the Childhood Cancer Survivor Study. Blood. 2011 Feb;117(6):1806-16.
Aleman BM, van den Belt-Dusebout AW, De Bruin ML, et al. Late cardiotoxicity after treatment for Hodgkin lymphoma. Blood. 2007 Mar;109(5):1878-86.
Swain SM, Whaley FS, Ewer MS. Congestive heart failure in patients treated with doxorubicin: A retrospective analysis of three trials. Cancer. 2003 Jun;97(11):2869–79.
Lefrak EA, Pitha J, Rosenheim S, et al. A clinicopathologic analysis of Adriamycin cardiotoxicity. Cancer. 1973 Aug;32(2):302-14.
Steinherz LJ, Steinherz PG, Tan CTC: Cardiac toxicity 4 to 20 years after completing anthracycline therapy. JAMA. 1991 Sep;266(12):1672-7.
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van Nimwegen FA, Ntentas G, Darby SC, Schaapveld M, et al. Risk of heart failure in survivors of Hodgkin lymphoma: effects of cardiac exposure to radiation and anthracyclines. Blood. 2017 Apr;129(16):2257-65.
Sleijfer S. Bleomycin-induced pneumonitis. Chest. 2001 Aug;120(2):617-24.
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Jóna Á, Illés Á, Szemes K, Miltényi Z1. Pulmonary alterations in Hodgkin lymphoma. Orv Hetil. 2016 Jan;157(5):163-73.
Horning SJ, Adhikari A, Rizk N, et al. Effect of treatment for Hodgkin's disease on pulmonary function: results of a prospective study. J Clin Oncol. 1994 Feb;12(2):297-305.
Hirsch A, Vander Els N, Straus DJ, et al. Effect of ABVD chemotherapy with and without mantle or mediastinal irradiation on pulmonary function and symptoms in early-stage Hodgkin's disease. J Clin Oncol. 1996 Apr;14(4):1297-305.
Haddy TB, Adde MA, McCalla J, Domanski MJ, Datiles M 3rd, Meehan SC, Pikus A, Shad AT, Valdez I, Lopez Vivino L, Magrath IT. Late effects in long-term survivors of high-grade non-Hodgkin's lymphomas. J Clin Oncol. 1998 Jun;16(6):2070-9.
Legha SS, Benjamin RS, Mackay B, et al. Reduction of doxorubicin cardiotoxicity by prolonged continuous intravenous infusion. Ann Intern Med. 1982 Feb;96(2):133-9.
van Nimwegen FA, Schaapveld M, Janus CPM, et al. Cardiovascular disease after Hodgkin lymphoma treatment: 40-year disease risk. JAMA Intern Med. 2015 Jun;175(6):1007-17.
20. Luursema PB, Star-Kroesen MA, van der Mark TW et al. Bleomycin-induced changes in the carbon monoxide transfer factor of the lungs and its components. Am Rev Respir Dis. 1983 Nov;128(5):880–3.
Comis RL, Kuppinger MS, Ginsberg SJ et al. Role of single-breath carbon monoxide-diffusing capacity in monitoring the pulmonary effects of bleomycin in germ cell tumor patients. Cancer Res. 1979 Dec;39(12):5076–80.
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23. Connors JM, Jurczak W, Straus DJ, et al. Brentuximab vedotin with chemotherapy for stage III or IV Hodgkin's lymphoma. N Engl J Med. 2018 Jan;378(4):331-44.
Radiance Research AcademyInternational Journal of Current Research and Review2231-21960975-52411213EnglishN2020July6HealthcareEvaluation of Dry Eye Disease Post-Cataract Surgery using Symptom Questionnaire and Tear Film Tests
English1924Jasmitha B. RajashekarreddyEnglish Pradeep T. ManchegowdaEnglish Varsha G BelamgiEnglishPurpose: To study the changes in ocular surface disease index and tear film tests for evaluation of dry eye among patients who have undergone cataract surgery.
Methods: A total of 123 patients aged more than 40 years undergoing cataract extraction were included. 87 of them underwent manual Small Incision Cataract Surgery(SICS) and 36 underwent Phacoemulsification(Phaco). Dry eye symptoms were evaluated using OSDI(Ocular Surface Disease Index) questionnaire, tear film assessment was done using Schirmer’s test 1, TBUT(Tear Film Break up Time) at baseline and 6 weeks after surgery. Relevant statistical tests were used to evaluate the significance of the variables.
Results: The overall incidence of dry eye using OSDI score was 29.26%, with mean OSDI scores of 13.85±9.83 and 23.12±14.54, pre and post-operative respectively a difference in score of 9.234 and significant P value (EnglishDry eye, Ocular surface disease index, Tear film tests, Cataract surgeryIntroduction:
Dry eye is a multifactorial disorder involving an ocular surface. It leads to significant morbidity due to its symptoms, commonly surface discomfort like foreign body sensation, pricking and gritty feeling, light sensitivity and visual disturbance. Disturbance in the osmolarity of the tear film and increase in the inflammatory mediators have been described as the common causes. Also chronic dry eye can lead to ocular surface damage1. Dry eye as a chronic disease has significant impacts on quality of life in elderly population. Several risk factors have been proposed for dry eye syndrome; amongthem older age, female gender, diabetes and high blood pressure are well-known causes.2,3 Many patients who have undergone cataract surgery have complaints of dry eye and main cause of dissatisfaction in such cases has been shown to be fatigue and foreign body sensation due to dry eye syndrome.
The ocular surface disease worsens most often after cataract surgery, multiple factors can contribute including transection of corneal nerves leading to loss of corneal sensations and impaired healing, damage to the corneal epithelium due to intense microscopic light exposure, prolonged irrigation of ocular surface with irrigating solutions, ocular surface irritation leading to an elevation in the inflammatory mediators and use of preservatives in topical anesthetic drops.4-6
Most common surgery performed in ophthalmic units being cataract surgery, and since senile cataract comprises most of the cataract surgery, the identification and management of ocular surface disease is therefore imperative.
Materials and methods:
A prospective observational study conducted at a tertiary center in South India, during the period of August 2019 and January 2020. All patients aged more than 40 years who underwent cataract surgery in the department of ophthalmology were included. Patients on topical or systemic medications known to cause dry eye, contact lens wearers, history of ocular surgery within last 6 months, systemic diseases associated with dry eye such as connective tissue disorders (Sjogren’s, rheumatoid arthritis), patients with any ocular disorder known to produce dry eye, acute ocular infections, impaired eyelid function like bell's palsy, lagophthalmos, ectropion were excluded.
An ocular surface disease index(OSDI) questionnaire was given to all patients before subjecting them to examination.OSDI questionnaire is a 12-item questionnaire used worldwide to accurately assess symptoms of ocular irritation related to dry eye and vision.7
Its reliability has been proved by literature.8The total OSDI score was calculated using the following formula: OSDI score= (sum of all answered questions) x 100/total number of answered questions) x 4. All subjects who were literate and understood the questionnaire were allowed to fill the forms independently, while subjects who are illiterate and whose vision was hampered enough to not being able to fill form independently were helped with translating into their own vernacular or simply read out the questions and responses were filled accordingly.
A detailed history, including demographic data, comprehensive ophthalmologic examination, assessment of best-corrected visual acuity (BCVA), ocular adnexal examination, the grade of cataract and the fundus examination, was done. All surgeries were carried out under local anesthesia by multiple experienced surgeons, SICS with superior scleral incision of 6-7 mm length with implantation of rigid PMMA(Poly Methyl Methacrylate) intra-ocular lens was implanted. Phacoemulsification with 3mm clear corneal supero-temporal incision was done with implantation of a foldable intra-ocular lens. Post-operative standard topical steroid and antibiotic regimen was followed for 3 weeks. Only cases with uneventful surgery were included in the study.OSDI questionnaire and ocular surface tests like Schirmer’s 1 and Tearfilm Break Up Time (TBUT) were done pre-operative baseline and repeated after 6 weeks of surgery.
Student t test has been used to find the significance of study parameters on continuous scale and Chi-square/ Fisher Exact test has been used to find the significance of study parameters on categorical scale.P value:P = 0.01 to 0.05 was considered moderately significant whereas P value : P=0.01 was considered strongly significant.
Results:
A total of 123 patients were included in the study, 87 patients (70.7%) underwent manual Small Incision Cataract Surgery (SICS) and 36 patients (29.3%) underwent Phacoemulsification (Phaco). Out of 123 patients, 67 patients (54.5%) were found to be Females and 56 patients (45.5%) were males. Demographic and clinical data are summarised in Table 1.
Pre and post-operative mean values of OSDI and tear film test scores are summarized in Table 2. Difference in pre and post-operative mean OSDI score among SICS group was 9.270 and P value of (Englishhttp://ijcrr.com/abstract.php?article_id=2698http://ijcrr.com/article_html.php?did=2698
The International Dry Eye Workshop.Ocul Surf .2007;5(2):75–193.
Schaumberg DA, Sullivan DA, et al. Prevalence of dry eye syndrome among US women. Am J Ophthalmol.2003;136:318–26.
Han SB, Hyon JY, Woo SJ, et al. Prevalence of dry eye disease in an elderly Korean population. Arch Ophthalmol.2011;129:633–8.
Hardten, D. R. Dry eye disease in patients after cataract surgery. Cornea.2008;27(7):855.
Ram, J, A. Sharma, et al.Cataract surgery in patients with dry eyes.J.Cataract Refract.Surg.1998;24( 8):1119-24.
Stulting RD, Mader TH, Waring III GO. Diagnosis and management of tear film dysfunction. 2nded. Philadelphia : Saunders;1998.482-500.
Walt JGRowe MMStern KL. Evaluating the functional impact of dry eye: the Ocular Surface Disease Index. Drug Inf J. 1997;311436.
Schiffman R, Christianson D, Jacobsen G, et al. Reliability and validity of the Ocular Surface Disease Index. Arch Ophthalmol.2000;118:615-21.
Shimmura S, Shimazaki J, Tsubota K. Results of a population-based questionnaire on the symptoms and lifestyles associated with dry eye.Cornea.1999;18:408-11.
The definition and classification of dry eye disease: report of the Definition and Classification Subcommittee of the International Dry Eye WorkShop (2007). Ocul Surf. 2007; 5: 75-92.
Begley CG, Caffery B, et al. Dry Eye Investigation(DREI ) Study Group. Use of the dry eye questionnaire to measure symptomsof ocular irritation in patients with aqueous tear deficient dry eye.Cornea.2002;21:664-70.
Kasetsuwan N1, Satitpitakul V, et al. Incidence and pattern of dry eye after cataract surgery. PLoS One.2013;8(11):1
Sitompul R, Sancoyo GS, Hutauruk JA, Gondhowiardjo TD. Sensitivity Change in Cornea and Tear layer due to Incision Difference on Cataract Surgery with Either Manual Small-Incision Cataract Surgery or Phacoemulsification. Cornea.2008;27(1):13-8.
Ram J, Gupta A, Brar GS, Kaushik S, Gupta A (2002) Outcomes of phacoemulsification in patients with dry eye. J Cataract Refract Surg 28:1386–9.
Chan-Ling T, Vannas A, Holden BA, O'Leary DJ. Incision depth affects the recovery of corneal sensitivity and neural regeneration in the cat. Inv Ophthalmol Vis Sci.1990; 31:1533-41.
Shimazaki J. Definition and diagnostic criteria of dry eye disease: historical overview and future directions. Investigative ophthalmology & visual science. 2018;59(14):DES7-12.
Li XM, Hu L, Hu J, and Wang W. Investigation of Dry Eye Disease and Analysis of the Pathogenic Factors in Patients after Cataract Surgery. Cornea. 2007; 26(1):16-20.
Kohlhaas, M., Corneal sensation after cataract and refractive surgery. J Cataract Refract. Surg.1998;24:1399-1409.
Radiance Research AcademyInternational Journal of Current Research and Review2231-21960975-52411213EnglishN2020July6HealthcareAn Ayurvedic Protocol to Manage Retinitis Pigmentosa - A Case Report
English2532Narayanan Namboothiri NarayananEnglish Aravind KumarEnglish Krishnendu SukumaranEnglish Agaja Peethambaran LeenaEnglishIntroduction: Retinitis pigmentosa (RP) is a clinically and genetically heterogeneous group of inherited retinal disorders that almost invariably occur in both eyes and often result in blindness in the middle-age and advanced age groups. According to Ayurveda, the cardinal symptoms of night blindness and diminished vision seen in RP may be correlated with Kapha-Vidagdha Drishti, a Drishtigata Roga or disease of vision.
Case: A 38-year-old male presenting with blurring of vision since 2017 and diminished night vision since childhood is presented here.
Intervention: The patient underwent two courses of in-patient Ayurvedic management consisting of Panchakarma (bio-purification) therapy, oral medicines, and external therapies for the eyes and head.
Results: Assessment showed improvement in both unaided distant visual acuity (DVA) and visual field analysis.
Conclusion: The main aim of management was to preserve and give a better quality of vision for the patient. The results indicate the potential of Ayurvedic treatments to manage and maintain vision in retinitis pigmentosa.
EnglishCase report, Retinitis pigmentosa, Kriyakalpa, Panchakarma therapyIntroduction
Retinitis pigmentosa is a genetically pre-determined retinal dystrophy characterized by progressive degeneration of rod photoreceptors, cone photoreceptors, and retinal pigment epithelium in that order. Inflammation, implied by the term is not a part of its pathophysiology. The prevalence of RP amounts to one case in every 4000 persons.1 A search on RP in PubMed amounted to 7000 references and was characterized by desirability for both experimental and clinical research.2 Occurrence may be either isolated or either autosomal dominant, autosomal recessive, or X-linked by inheritance. Apart from genetic predisposition, there are no other known risk factors.3 RP's primary symptom is night blindness, with advanced cases presenting with a ring-like scotoma in the visual field that gradually progresses to "tunnel" vision. As there is no definite cure for RP in allopathic medicine, alternative management options may be explored.
Methodology
The efficacy of an Ayurvedic treatment protocol to manage a case of RP was assessed in this report. It was prepared according to the Case Report (CARE) guidelines to ensure transparency and effectiveness in reporting4. Although institutional ethical clearance was not required for this study, written informed consent was obtained from the patient before detailing his case.
Case Presentation
A 38-year-old non-diabetic and non-hypertensive male presented to the OPD of Sreedhareeyam Ayurvedic Eye Hospital and Research Center, with blurring of vision since 2017 and difficulty in night vision since childhood. He was born to non-consanguineous parents and his mother had a full-term, normal delivery (FTND) with no postpartum complications. He started to gradually develop difficulty in night vision around the age of 3, for which he was prescribed vitamin A tablets. He developed pain in distant vision around the age of 7, for which he was diagnosed with myopia and prescribed corrective spectacles. The glass power progressively increased over time, for which he was prescribed cylindrical lenses in 2014. In 2018, he was diagnosed with retinitis pigmentosa after a complete ophthalmic and genetic examination. He was advised to protect his eyes from ultraviolet radiation, avoid smoking, and take plenty of fruits, vegetables, and foods rich in omega-3 fatty acids. Genetic counseling was also recommended. He had his first consultation at Sreedhareeyam Eye Hospital in September 2018.
His sister also suffered from night blindness. His bowel, appetite, and micturition were normal and his sleep was sound. He occasionally consumes alcohol. Review of systems and vital signs were normal. He weighed 90kg and was 172cm tall. His Dasavidha Pariksha (ten parameters of examination)5 findings are listed in Table 1.
Unaided distant visual acuity (DVA) was LogMAR 0.602 in both eyes (OU). Aided DVA was LogMAR 0.477 in the right eye (OD) and LogMAR 0.301 in the left eye (OS), which was improvable to LogMAR 0.301 OU with a cylindrical lens of 1 diopter OD and 1.25 diopter OS. Near vision was N6 OU. Anterior segment examination was normal OU. Direct and consensual pupillary reflexes were normal OU.
Posterior segment examination by direct ophthalmoscopy showed a slightly cloudy foveal reflex OU, pale optic disc OU, normal macula OU, and some bony corpuscles in the peripheral retina OU. Visual field analysis OU showed marked constriction in the peripheral visual fields (Figures 1 and 2). The findings were suggestive of RP.
The intervention adopted reflected the treatment for Timira and Kacha according to Vagbhata, viz., administrations of Snehana (therapeutic oleation), Asra-visravana (blood-letting), Reka (purgation), Nasya (medication through the nasal route), Anjana(collyrium), Murdha-basti (retention of oil over the head region), Basti Kriya (therapeutic enema), Tarpana (lubrication of the eye), Lepa (anointment), and Seka (ocular therapy by streaming).6
The patient’s first round of treatment was from 25/09/2018 - 15/10/2018, and his second round of treatment was from 12/08/2019 - 22/08/2019. Oral medicines such as Kvatha (decoction), Ghrta (clarified butter), and tablets (Table 2); Panchakarma therapies such as Snehapana (therapeutic oleation), Svedana (sudation therapy), Virecana (therapeutic purgation), and Marsa Nasya (high dose medication through the nose) (Table 3); and external therapies for the eye (Netra Kriyakalpa) and head such as Netradhara (ocular therapy by streaming), Hasta Pada Abhyanga (therapeutic massage over the hands and feet), Pratimarsa Nasya (low-dose medication through the nasal route), Anjana, Sirodhara (therapeutic streaming over the head), Ascyotana (eye drops), Siro-veshtanam (application of paste over the head on a Cora cloth), Bandhana (bandaging), Mukha Dhanya Pinda Sveda (facial sudation by applying poultice made from sour grains), Drishti Prasadana (massage over the eyelids using ghee), and Netra Tarpana (lubrication of the eye) (Table 4) were prescribed during the two courses of treatment.
During Snehapana, the patient was advised to observe strict rest and abstain from consuming oily and fried foods. A total of 5 Vegas (urges) were noted between 6:30am and 11:30am during Virecana, after which, Peya (thin gruel of rice) was administered as Samsarjana Krama (post-therapy dietetic regimen for revival).
All medicines, except Septillin tablet, were manufactured at Sreedhareeyam Farmherbs India, Pvt. Ltd., the hospital’s GMP-certified drug manufacturing unit. Septillin Tablet was manufactured by The Himalaya Company, based in Bengaluru, Karnataka, India.
Result
DVA was LogMAR 0.477 OU, which was improvable to LogMAR 0.176 OU with cylindrical lenses of -1.25D OD and -0.5D OS after the first course of treatment on October 15th, 2018. NVA was maintained at N6 OU. The same visual acuity was maintained at admission to, and at discharge after, the second course of treatment. Refraction at discharge after the second course of treatment demonstrated LogMAR 0 OU with cylinder lenses of -1.25D OD and -0.5D OS. Fundus examination by ophthalmoscopy showed no further progression in the attenuated blood vessels and bony corpuscles. Visual field analysis showed markedly wider peripheral visual fields OU (Figures 3 and 4).
A timeline of events for this case is provided in Table 5.
Discussion
Ayurveda explains that genetic diseases, which are a result of abnormalities in the Bija (sperm or ovum) brought about by improper activities of the parents and divine providence, increase all the Doshas and the resultant condition, as well as all hereditary conditions, is Asadhya (incurable).12 Hereditary defects in an organ happen when it is vitiated due to the part of the Bija responsible for the formation of that organ becoming vitiated itself.13 In this patient, a genetic defect resulting in retinitis pigmentosa occurred despite a normal pregnancy and delivery course.
Kapha Vidagdha Drishti occurs when the person perceives objects as white due to the Doshas lodging in the first and second Patalas (layers of the eyeball). When the Doshas advance to the 3rd Patala, the person sees during the day and not at night because of Kapha Dosha.14
Snehapana was done as a Samana Cikitsa (pacifying treatment) for this patient, with 30mL of ghee administered each day so as to not increase Kapha further. Avipattikara Yoga was selected for Virecana as it is apt for all Pitta (Dosha responsible for regulating body temperature and metabolic activities) conditions. The ingredients of Jivantyadi Taila pacified Vata and Pitta. Saptamrta Lauha is Tridosha Prasamana (pacifies the Tridosha), Rakta Prasadana (enhancing the quality of blood tissue), Rasayana (rejuvenative), and Cakshushya (Dravya or intervention good for eyesight). Asvagandha is Kapha-Vata Samana (pacifies Kapha and Vata), Balya (strength, stamina, and immunity promoter), Rakta Prasadana, and Rasayana. These medicines enhanced blood quality, relieved Tridosha, and prolonged the retinal dystrophy by revitalizing the tissue. Bharngyadi Kvatha is Vata-Kapha Samana, Dipana, and Srotosodhana (cleansing the structural or functional channels). Dasamula Katutraya Kvatha is Vata-Kapha Samana, Dipana, and Lekhana (therapeutic scraping). Sudarsanam Tablet, the tablet form of the original Curna, is Tridosa Prasamana, Amapacana (enhancing digestion). The combined effect of these three medicines helped to enhance digestion, reduce Doshas, and make available essential nutrients by clearing the channels. Local external treatments enabled efficient absorption and transport of the medicines to the target tissue, the retina, by obviating the blood-aqueous, blood-vitreous, and blood-retinal barriers.
Siroveshtanam is a variant of Sirolepa in which the paste is applied to the head in a Cora cloth and tied in the following manner: One end is placed over the right ear, the cloth is wrapped over the forehead and towards the left ear, taken over the back of the head toward the occiput, and brought over the head towards the right ear. Drishtiprasadanam is a procedure in which lukewarm Sneha is taken and massaged over the forehead and eyelids while applying pressure to the forehead, inner and outer canthus, and the supraorbital notch. Kasyapam Kvatha and Saptamrta Kvatha are indicated in all Netra Rogas (eye diseases). Timiranjana, Nakulanjana, and Nayanamrtam are Sita Virya (potency of coldness) and Ropana (healing) by nature. Sasanka Taila is Sita Virya by nature, and pacifies Pitta Dosha. Vinayakanjana is Ropana and is indicated in all Netra Roga. Jatavedha Ghrta and Ananta Ghrta are excellent for Netra Tarpana (lubrication of the eye).
Conclusion
The main challenge, in this case, was maintenance of vision and prolonging the dystrophy. However, positive results were obtained in both fields after two courses of Ayurvedic treatment. Repeated courses of treatment may aid to at least maintain vision and prolonging further progression of the disease. The results obtained in this case may be validated and analyzed by large-scale studies and trials.
Abbreviations:
RP: retinitis pigmentosa
DVA: distant visual acuity
NVA: near visual acuity
OD: oculus dexter
OS: oculus sinister
OU: oculus uterque
Acknowledgment:
The authors thank Sreedhareeyam Ayurvedic Eye Hospital and Research Center, and Sreedhareeyam Farmherbs India Pvt. Ltd., for their help in preparing this case report. The authors acknowledge the immense help received from the scholars whose articles are cited and included in references of this manuscript. The authors are also grateful to the authors/editors/publishers of all those articles, journals, and books from where the literature for this article has been reviewed and discussed.
Conflicts of Interest: None declared
Sources of Funding: None declared
Englishhttp://ijcrr.com/abstract.php?article_id=2699http://ijcrr.com/article_html.php?did=2699
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Parmeggiani F, Clinics, Epidemiology, and Genetics of Retinitis Pigmentosa, Current Genomics, June 2011, Vol. 12, Issue 4, pgs. 236-237
Lim IJ, Akkara JD, Epley D, Shah VA, Carrera W, 2019, Retinitis Pigmentosa, Retrieved from https://eyewiki.aao.org/Retinitis_Pigmentosa
Gagnier J, Kienle G, Altman DG, Moher D, Sox H, Riley DS, CARE group, The CARE guidelines: Consensus-based clinical case-reporting guideline development, Global Advances in Health and Medicine, 2013, Vol. 2, Issue 5, pgs. 38-43
Byadgi PS, Ayurvediya Vikrti Vijnana and Roga Vijnana, Vol. 1, Chaukhambha Orientalia, Varanasi, 2004, pg. 300
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Murthy PHC, Sarngadhara Samhita: Text with English Translation, Chaukhambha Orientalia, Varanasi, 2010, pg. 156
Murthy KRS., Ashtangahrdaya of Vagbhata: Text, English Translation, Notes, Appendices, and Index, Vol. II, Nidana, Cikitsa, and Kalpa-Siddhi Sthana, Krishnadas Academy, Varanasi, Reprint 2000, pg. 540
Krishnan Vaidyan KV, Gopala Pillai S, Sahasrayogam: Sujanapriya Commentary, Vidyarambham Publishers, Alappuzha, 2006, pg. 286
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Murthy KRS., Ashtangahrdaya of Vagbhata: Text, English Translation, Notes, Appendices, and Index, Vol. II, Nidana, Cikitsa, and Kalpa-Siddhi Sthana, Krishnadas Academy, Varanasi, Reprint 2000, pg. 67
Sharma RK, Dash B, Caraka Samhita: Text with English Translation and Critical Exposition based on Cakrapani Datta’s Ayurveda Dipika, Vol. II, Nidana, Vimana, Sarira, and Indriya Sthanas, Chaukhambha Krishnadas Academy, Varanasi, Reprint 2005, pg. 382
Sharma PV, Susruta Samhita: With English Translation of Text and Dalhana’s Commentary alongwith Critical Notes Vol. III: Kalpasthana and Uttara Tantra, Chaukhambha Vishwabharati, Varanasi, Reprint 2010, pg. 145
Radiance Research AcademyInternational Journal of Current Research and Review2231-21960975-52411213EnglishN2020July6HealthcarePathophysiologic Enigma of COVID-19 Pandemic with Clinical Correlates
English3337Sana ParveenEnglish Shraddha JainEnglishIntroduction: This review article examines the virology, modes of transmission, risk factors, clinical course, diagnosis and treatment of Coronavirus disease based on the various studies done in the past 8 months.
Background: Covid-19(Coronavirus disease 2019) has been named as a novel virus as there has been no known cases of infection with this strain in human beings. Origin of this virus is alleged to be from a family of bats and pangolins, in Wuhan, China in Dec 2019 from a seafood market, and since then the spread of this virus has been unstoppable.After a single introduction into the human population, the Chinese authorities immediately notified the WHO about the increasing number of COVID -19 cases. An epidemic was caused due to the SARS virus in China in 2003, and hence this virus has been renamed as SARS-Cov-2 because of its close relation to it. The symptoms of this disease can vary from mild flu-like to severe respiratory distress requiring admission to ICU.
Methods: The literature on COVID-19 was retrieved from PubMed, Google Scholar and Cochrane database. Keywords and phrases used during the search included “Covid-19,” “pandemic,” “Novel” and “Coronavirus”.
Conclusion: At present, no definitive treatment is available for this virus; only symptomatic management is undertaken. Further research is being undertaken to develop the Coronavirus vaccine and the use of plasma of treated patients to manage active infected cases.
EnglishCOVID, Pandemic, Seafood, Recombination, Zoonotic spilloverIntroduction –
The virus has been named so attributing to its crown like appearance under microscopy. Coronaviruses are positive sense single stranded RNA enveloped viruses.1Till now, four genera namely - a, b, g, d, have been identified. The novel-b Coronavirus shows maximum similarity to the genomic sequence of two bat-derived (SARS)-like coronaviruses. This virus was then named “SARS-CoV-2” by theInternational Virus Classification Commission on February 11, 2020 also known as COVID-19 – acronym for coronavirus disease. The spread of the virus began in December 2020 and since then, it has spread to more than 203 countries, infecting more than 10 million people and causing mortality in several nations. Apart from this, there have been two more epidemics in the past two decades due to coronaviruses namely, SARS- severe acute respiratory syndrome and MERS- Middle East respiratory syndrome.2
The phenomenon of “Zoonotic Spillover” and “Recombination”
The most probable site of isolation of the virus are the seafood markets of Wuhan, China. Wild animals over here are sold as pets and delicacies or kept in captivity. Animals and human beings are kept in close contact with each other in this area, due to which a disastrous mixture of various species and viruses can occur. This has led to the phenomenon known as “Zoonotic Spillover”.3
Two mechanisms namely antigenic drift and shift, have been implicated in giving rise to the pandemic status of the novel Coronavirus. Antigenic drift is when many small mutations occur and accumulate over time to give rise to different strains of a virus. Many scientists suggest that the SARS-Cov-2 virus is formed as a result of a recombination between two viruses, one which is close to the bat virus and the other similar to the pangolin virus. It is a chimera between two pre-existing viruses, also known as antigenic shift, which is also seen in many influenza viruses. Various studies have already explained this recombination mechanism.4 Recombination is the process by which a new virus develops which results in infection of a new host species. For this to occur, the two different viruses should infect the same organism at the same time.
Pathogenesis-
The most commonly identified route of entry of the virus into the human body is through the nostrils i.e. aerosol borne ; second one being fomites i.e. surfaces that frequently coming in contact with human skin which can transmit the infection to another person and hence the transmission rate is very high for this infection. The most important predictor of virus entry into host cells has been reported to be Coronavirus S Protein. There is direct fusion between the virus membrane and the cell plasma membrane by which there is entry of the virus.
New envelope glycoproteins are formed and inserted into the ER or Golgi apparatus, and the formation of nucleocapsid takes place by the combination of nucleocapsid protein and genomic RNA. Then germination of viral particles occurs and vesicles are formed which fuse with cell membrane to release the viral particles.5
Antigen presentation in coronavirus infection-
Upon entry of the virus in the cells, its antigen is presented to the antigen presentation cells(APC) which is done by major histocompatibility complex (MHC; or human leukocyte antigen(HLA) in humans) and then identified by virus-specific cytotoxic T lymphocytes (CTLs). The antigen presentation of SARS-CoV mainly depends on MHC I molecules, but studies have shown that MHC II also contributes to its presentation.
Humoral and cellular immunity -
Like common viral infections, the antibodies against SARS-CoV virus have a typical IgM and IgG production. At the end of 12 weeks, the S-specific IgM antibodies disappear, while the IgG antibodies can last for a longer time. The antibodies produced are primarily S-specific and N-specific. Various reports suggest that the number of CD4þ and CD8þ T cells in the blood of SARS-CoV-2-infected patients is reduced.5 which is also seen in the acute phase response. Studies have shown that even in the absence of an antigen, CD4þ and CD8þ memory T cells can persist for four years in a part of SARS-CoV recovered individuals and can perform T cell proliferation.5
Cytokine storm in COVID-19 -
ARDS is the commonest end event for all three identified Coronaviruses namely; SARS-CoV-2, SARS-CoV and MERS-CoV infections. IFN-g, IFN-a, TNF-a, and TGF b are pro-inflammatory cytokines, which, along with CCL2, CCL3, and CCL5, are chemokines released in a huge quantity by macrophages, monocytes, lymphocytes and platelets in this infection. This gives rise to a severe uncontrolled inflammatory response, known as cytokine storm. The immune system violently attacks the body, which many studies have suggested that is supposedly an allergic response due to the chemokines. It, in turn, can cause multiple organ failure, and ultimately lead to death.5
4 . Evasion of immune system
Many strategies are used by Coronavirus to ensure immune evasion and escape destruction by the host cells. Modification of pattern recognition receptors and the ability to affect antigen presentation are ways by which they avoid detection by the antigen presenting cells. Studies have also shown that gene expression related to antigen presentation can also be down-regulated by the MERS-CoV infection.
Virus structural protein binding porphyrin-
Recent studies have shown that the virus has few structural proteins which can bind the porphyrin in heme and reduce the oxygen binding capacity of haemoglobin, ultimately leading to hypoxia. This can further give rise to cardiac as well as neurological symptoms in the patient like- stroke, decreased consciousness, myopathy and loss of sense of smell or taste.5,6
Clinical features-
The clinical manifestations of this disease range from being asymptomatic to rapidly progressing disease. It has been noted that most of the cases are mild to moderate and around 4% of the cases only progress to fulminant disease, suggesting that the mortality rate is much lower than MERS and SARS infections. Symptoms begin with a fever, cough, sore throat, nasal discharge and obstruction along with myalgia. Rarely a patient can present with headache and diarrhoea as the only symptom as some studies have suggested. About 50% of the patients had dyspnoea (median duration- 8 days). Lymphocytopenia was seen in 63% of patients.7Complications like acute respiratory distress syndrome, secondary infections and acute heart injury were also present. Few of the patients required to be treated in the ICU with ventilator support. The median incubation period was 14 days, which is also the suggested quarantine period for any infected patient. Studies have shown that among confirmed cases, maximum were aged 30-79 yearsand had mild/moderate pneumonia.8
Diagnosis –
Physical examination
The infected patients have symptoms like dry cough, difficulty in breathing, fever, nasal congestion, runny nose or other upper respiratory tract symptoms. Recent researches have also shown that the disease can also present with anosmia, hyposmia and dysgeusia .9
Imaging-
Chest x-ray: In mild cases, chest X-Ray is suggestive of many small patches and interstitial changes, remarkable in the lung periphery. Ground-glass opacities, shadows with or without pleural effusion, can be present in high risk cases.CT scan of the thorax of the infected patients was suggestive of - ground-glass opacity and consolidation in both lungs, especially in the lung periphery. Multiple lobar lesions can be present in both lungs in children with severe infection.10
Laboratory diagnosis-
The definitive diagnostic modality is collection of nasopharyngeal and oropharyngeal swabs sent for RT-PCR testing followed by subsequent isolation of the suspected patient. ENT specialists usually take the test and they should be standing on the side of the patient while enduring the swab to prevent direct aerosol contact from the patient. The person receiving the sample must be wearing complete Personal Protective Equipment.11
To collect the oropharyngeal sample, the swab is moved along the back of the throat as well as bilateral tonsillar beds. In the nose also the same swab is used in order to conserve swabs, below the inferior turbinates up to the nasopharynx. These samples contain high viral loads, and hence should be used for testing wherever possible. In some cases, endotracheal aspirate, broncheoalveolar lavage can also be taken, where lower respiratory samples are needed. Currently, the time taken for the results is around 48 hours. Various labs have been developed to give the results in fastest time, namely -Neuberg Diagnostics, Oncquest, Mylabs, which conduct the test by Rapid Diagnostic Test Kits (RDT), which gives the test results in 45 minutes. Till then the patient is kept in isolation in order to prevent the spread of the infection in case the patient turns out to be positive.12
Treatment-
Various guidelines have been given by the WHO and the CDC for managing the patient.
A COVID suspect is defined as any person with -
A study published in “The Lancet” states that the lesser severity of coronavirus impact may be linked to national policies on BCG childhood vaccination, while citing the examples of multiple randomised control trials conducted in Netherlands and Australia12. Currently, no specific drug or vaccine is available for this viral infection. Only symptomatic treatment consisting of anti-allergics, antipyretics, rest and isolation is advisable.13
Ongoing research is suggestive of the presence of an mRNA sequence found in Southeast Asian population, which has been known to be protective of this virus. Hence, the reason why not very severe cases of pneumonia or ARDs have been reported in this population. Many US scientists have suggested that the Bacillus Calmette-Guerin (BCG) vaccine, administered to Indian children soon after birth in an attempt to protect against tuberculosis, could be a "game-changer" in the fight against the deadly coronavirus.14
Chloroquine- an antimalarial has been implicated in reducing the severity of the acute immune response by the virus, but further research is required in order to identify the risk-benefit ratio as some cases of death due to Q-T prolongation followed by sudden cardiac arrest have been reported after some doctors took the drug as a prophylactic.15 Few scientists have found that immunosuppressive drugs like Tacrolimus and Prednisolone can help reduce the immune response and prevent the patient from developing a strong reaction to the virus, as seen in patients of solid organ transplantation affected with COVID-19.16
Also, further studies are being conducted to isolate the plasma of treated COVID patients, which can be used to treat active symptomatic patients. Numerous clinical trials are ongoing in Wuhan, Maryland and other places, to develop a vaccine for this pandemic causing virus.17,18
Measures to control and prevent transmission of infection –
As advertised by the WHO and the government authorities of multiple countries, two main steps are extremely crucial to control the spread of this virus-
Social distancing and handwashing.
Social distancing means maintaining at least a distance of 6 feet from other people and handwashing practiced for at least 20 seconds and with all the proper steps. This has been achieved by stringent measures like a two month lockdown in India as well as China, closure of schools, colleges, any sort of public gatherings, movie halls etc. along with strict action taken by the government if these rules are not obeyed.19Since exact treatment is not known yet, the best way to be protected from this virus is by preventing it, researchers say. For healthcare providers of known /suspected COVID patients- it is essential to wear personal protective equipment and follow proper guidelines for putting on and taking off the PPE.
Areas of further research –
It is important to determine in which organism did the recombination occurs, (pangolin / bat/another species) and under which environmental conditions it took place.
Drugs can be developed to target the S protein or inhibit the virus's entry into the human cell. Along with that destroying the immune evasion mechanism of this virus is crucial in its specific drug development.20
The plasma of COVID treated patients can be isolated and used in the treatment of actively infected cases; further studies need to be done in this area. Also by studying the T-cell responses in patients, development of vaccines can be done, which imperative during this time.
Discussion
The Coronavirus has emerged as an extremely virulent pandemic, causing disruption of lives of thousands of individuals all over the world. Because of the lockdown which has been imposed in different parts of the world, a significant amount of mortality has been prevented, especially in developing countries like India. The coming two weeks will be quite crucial for this country as the incubation period will be over and due to the relaxation in the lockdown, symptomatic patients will start coming in.
Conclusion
The onset of this new disease has cost us almost 2 lakh lives and as on May 9, 2020, there are more than 33 lakh cases, out of which around 5 lakh will require ventilatory support in the coming weeks. With a sudden shock to the healthcare sector, there has been a tremendous loss to the economy, finances of the nations, loss of wages to the daily wagers, and business shutdown. If managed in an organised way, there’s a way out of this viral situation.
Acknowledgement- We acknowledge the support of our institution Datta Meghe Institute of Medical Sciences; and the Department of Research and Development of our university for all the help lent in preparing and submitting this manuscript.
Sources of funding – None.
Conflicts of interest - Nil
Englishhttp://ijcrr.com/abstract.php?article_id=2700http://ijcrr.com/article_html.php?did=2700
Remuzzi A., Remuzzi G. COVID-19 and Italy: what next?', Health Policy. Published Online. March 12, 2020. https://doi.org/10.1016/S0140-6736(20)30627-9
Zhou F., Yu T., Du R., Fan G., Liu Y., et al. ; Clinical course and risk factors for mortality of adult inpatients with COVID-19 in Wuhan, China: a retrospective cohort study. Lancet 2020; 395: 1054–62 2020
Decaro N., Lorusso A. et al.; Novel human coronavirus (SARS-CoV-2): A lesson from animal coronaviruses Vetinerary Microbiology. 2020 May; 244: 108693. Published online 2020 Apr 14. doi: 10.1016/j.vetmic.2020.108693
Graham R.L , Baric S. R. Recombination, Reservoirs, and the Modular Spike: Mechanisms of Coronavirus Cross-Species Transmission. Journal of Virology Mar 2010, 84 (7) 3134-3146;
Liu W., Li H . COVID-19: Attacks the 1-Beta Chain of Hemoglobin and Captures the Porphyrin to Inhibit Human Heme Metabolism. posted online on chemrxiv.com
Green A.J., Josephson S. A The Spectrum of Neurologic Disease in the Severe Acute Respiratory Syndrome Coronavirus 2 Pandemic Infection Neurologists Move to the Frontline.JAMA Neurol. Published online April 10, 2020. doi:10.1001/jamaneurol.2020.1065
Pambuccian S.E. The COVID-19 pandemic: Implications for the cytology laboratory. Journal of the American Society of Cytopathology 2020; March 23 2020 https://doi.org/10.1016/j.jasc.2020.03.001
Verity R., Okell L.C. , Dorigatti I., Winskill P .,Estimates of the severity of coronavirus disease 2019: a model-based analysis Lancet Infect Dis 2020 March 30, 2020. https://doi.org/10.1016/S1473-3099(20)30243-7
Kaye R, Chang D, Kenzhaya K, COVID-19 Anosmia Reporting Tool: Initial Findings. American Journal of Otolaryngology and Head and Neck surgery. April 28, 2020. Published online. https://doi.org/10.1177/019459982092299
Adhikari S.P., Mengh S., Wu Y. et al.., Epidemiology, causes, clinical manifestation and diagnosis, prevention and control of Coronavirus disease (COVID-19) during the early outbreak period: a scoping review. Infectious Diseases of Poverty volume 9, Article number: 29 March 17 (2020). https://doi.org/10.1186/s40249-020-00646-x
Leitmeyer K., Zambon M., et al. Laboratory testing for coronavirus disease (COVID-19) in suspected human cases. WHO Interim Guidance. Published online on March 19, 2020.
Curtis N., Sparrow A., et al., Considering BCG Vaccination to lesser the impact of COVID-19. The Lancet. Volume 395, p1545-1546 . May 16, 2020.
Chavez S., Long B. , Koyfman A. et al., Coronavirus Disease (COVID-19): A primer for emergency physicians, American Journal of Emergency Medicine (March 22 2020), https://doi.org/10.1016/j.ajem.2020.03.036
X. Li et al., Molecular immune pathogenesis and diagnosis of COVID-19, Journal of Pharmaceutical Analysis, https://doi.org/10.1016/j.jpha.2020.03.001
Moore N., Chloroquine for COVID-19 Infection. Nature Public Health Emergency Collection. 2020 April 7. p 1–2. doi: 10.1007/s40264-020-00933-4 [Epub ahead of print] .
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Mak E., China approves first homegrown COVID-19 vaccine to enter clinical trials. BioWorld. Retrieved March 24 2020.
Rodriguez-Morales A.J., et al., Clinical, laboratory and imaging features of COVID-19: A systematic review and meta-analysis. Travel Medicine and Infectious Disease, March 13, 2020. https://doi.org/10.1016/j.tmaid.2020.10162
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Radiance Research AcademyInternational Journal of Current Research and Review2231-21960975-52411213EnglishN2020July6Healthcaree-ICU's/Tele ICU's, it's Role, Advantages Over Manual ICU's and Shortcomings in the Current Perspective of Covid-19 Pandemic: A Critical Review
English3845Naresh RathodEnglish Aashishsingh RajputEnglish Fouzia MEnglish Jyothi D BEnglish Kalyani PatilEnglishThe Coronavirus disease 2019 (Covid-19), is a viral pandemic that emerged in the Wuhan city of Hubei province in China, as a cross-transmission between bats and human beings. This is spreading exponentially across the globe, claiming lakhs of life worldwide and the counting is on. In view of this, there is increased risk and substantial burden on healthcare, and the Intensive healthcare community must prepare themselves to tackle this crisis. As this disease results in rapid deterioration of an individual's health status, without any warning signs, the burden on ICU's might be unexpectedly higher if more individuals become critically ill at the same time. In this context, the traditional mode of ICU operation might not meet the demands; hence technological advancements in the form of e ICU's or Tele ICU's may be the next visionary step. This model could tackle several interconnected e ICU's simultaneously with only a few dedicated teams of multidisciplinary specialist from a remote place and a very few bedside functionaries. This model may be advantageous to cut down the risk of infection due to ICU overcrowding, challenges with deficient PPE's, physical burnout and psychological breakdown of healthcare professional. This would also ensure round the clock uninterrupted services without compromising in the quality of care, viz a viz, substantially reducing the healthcare costs and financial burden on the management in the long run. Although met with technical challenges and shortcomings of lack of software personnel and round the clock high speed connectivity issues, the benefits of e ICU outweigh the risks involved. Hence the government, regulatory bodies and healthcare management must give a deep thought on revolutionizing age-old ICU models to technologically advanced e ICU's that may cater to a larger population with limited intellectual resources in a crisis like Covid-19 pandemic.
Englishe ICU, Tele ICU, Telemedicine, Covid-19, PandemicINTRODUCTION
` In the current perspective, the world is facing a dreaded pandemic, with a major toll on the lives and economy across the globe. Coronavirus disease 2019 (COVID-19) is the third coronavirus infection in the past two decades, that occurred originally in Asia, after severe acute respiratory syndrome (SARS) and Middle East Respiratory Syndrome (MERS). COVID-19, emerged as an epidemic, to later spread globally as a pandemic in a very short period of time, it is presumed to have originated from the Wuhan city of china in the Hubei province, due to cross-transmission between bats and humans. History traced some major pandemic like the Spanish flu in 1918, which caused over 20 to 50 million deaths worldwide. In the year 1957-58 Asian flu pandemic occurred, which was triggered by influenza A (H2N2) virus's new strain, thought to have originated from East Asia, claiming the lives of over 1.1 million individuals worldwide. In 1968, Hong Kong flu pandemic triggered by new strain of H3N2 virus claimed lives of 1 Million people across the globe. 2009-10 the world witnessed swine flu pandemic (H1N1), which was triggered by a new strain of similar virus thought to cause Spanish flu. This pandemic affected almost 700 million to 1.4 billion people, but the mortality rates were comparatively lesser. Presently in May 2020, 5 million people have been reported to be infected with Covid-19, with death tolls touching a figure of 3 Lakhs and counting.1
Symptoms of Covid-19 disease vary from individual to individual depending upon the viral load and immunity profile, it may range from fever, fatigue, tiredness and dry cough. The patient may also complain of malaise, nasal congestion, sore throat, headache, difficulty in swallowing, dysgeusia, diarrhea, anosmia, tinnitus, breathlessness and chest pain. Few individuals may get infected with this disease and still remain asymptomatic or with mild flu like symptoms, but they are potential candidates for transmission to other humans, it is presumed that almost 80% of the people recover from illness without needing specialized intervention, whereas the rest 20 percent, would invariable land up in severe complications like, severe hypoxemia, failing respiration, ARDS, followed by cytokine storm, leading to vascular hyper-permeability, multiorgan failure and eventually death of the individual. Elderly people with chest and cardiac co-morbidities like cardiac disease, high blood pressure, diabetes and immune-compromised states are more likely to succumb to the illness and mortality among these people are generally higher. These individuals require specialised care and prompt intervention in an ICU setup for an approximate period of 7 to 14 days or higher, depending upon the criticality of the patient.2
As Covid-19 is a highly contagious viral pandemic, with tolls rising exponentially combined with inherent challenges like global shortage of medical masks and respirators, Personal Protective Equipment’s (PPE), deficient healthcare staffs, Shortage of ICU beds and increase in the workload, burn out, stress, medical leaves, quarantine of professionals post exposure to Covid-19 and the lack of technological advancements across ICU’s pose a grave challenge in management of terminally ill patients requiring ICU care.
Tele-ICU/eICU models are already operational in countries like, Italy, Japan, Malaysia, USA for treating various emergencies condition even before the outbreak of Covid-19 pandemic. Although these countries were well-versed with the technical and procedural management of eICU still some countries like Italy, USA they were unable to accommodate the vast majority of critically ill patients of Covid-19, which demanded treatment and intervention in an ICU setup. This could be due to lack of extensive availability of eICU across the country or deficient skilled man power to operate them or both. In Indian healthcare system eICU concept is operational in few hospitals Fortis and Apollo hospitals located in metropolitan cities since a couple of a years ago. This concept has not gained momentum due to cost consideration, appreciation of technological advancements in management of critical care illness, lack of skilled professionals, and lack of need for implementation of this model on a larger scale in a revenue constraint environment. In a deadly pandemic like Covid-19 which is highly contagious and easily transmissible by airborne route and through fomites maintaining social distance and restricting undue doctor-patient interaction is considered the best practice. In such scenario the role of eICU is much appreciated which cuts across most of the risk factor in transmission of Covid-19. Hence, to manage pandemic effectively more number of eICU needs to be established across pan India. That would enable a limited number of skilled staff to manage critical care emergency in vast majority of Covid-19 infected individuals. But this may be faced with challenges of budget and infrastructural constraint in an economic downfall.
PANDEMIC AND ITS TOLL ON HEALTHCARE WORKERS
Throughout the globe, the healthcare workers fighting this situation on the frontlines have a grim story to tell about the scarcities of life-saving health supplies, including PPE's and stories of death. Across the globe, social media is showcasing the hazardous consequences upon the healthcare professional despite the usage of PPE’s. Mortality of healthcare professionals are on the rise and counting. Europe and Asian statistics estimate that around 3000 health professionals in China, 6000 in Italy and 5400 in New York health workers are infected due to COVID-19.16 While America being in the same path still have the unclear statistical data of COVID-19 infected healthcare professionals because they lack the key data which clarifies the exact figures at the moment. Country like India with a population of 1.3 billion people tends to live in the different states with different socio-economic backgrounds, in spite of having quick disaster alleviation plan of announcing early lockdown, social distancing, quarantine and isolation plan, hygiene management, and instructions of wearing mask is still seen in steady elevation in the number of positive cases of COVID-19 which are inclusive of healthcare professionals. In spite using full or minimum Personal Protective Equipment's at their expense. This proves that the virus is highly contagious and easily transmissible from one individual to another or through objects/surfaces to individuals, not clearly described yet. More study and research need to be done in order to understand the precise mechanism of transmission of virus thoroughly.3
In the current scenario, despite the non-pharmaceutical interventions like social distancing and etc., minimizing the load of virus should be the key strategy to reduce the transmission. For this, there should be patient doctor interaction without compromising the safety of the already deficient healthcare professionals and its subsequent quality of care. This should overall help to reduce the viral load and transmission of infection. eICU plays an important role in this context, that can majorly tide across these inherent barriers.
GLOBAL CHALLENGES WITH REGARDS COVID-19
The world is facing a global shortage in the availability of medical masks and respirators for the warriors tackling the disease in the forefront and the general public as a whole, this threatens the efforts to prevent the transmission of the disease. N95 respirators that don't fit the facial contours might not provide necessary protection and may increase the risk of forefront warriors succumbing to the infection. There is a global short of PPEs, that further adds the risk of viral infection; on the other hand self-contamination during the removal of PPEs poses another challenge. In ICU set up, Viable virus on the surface of the mask, PPEs, mobile phones, or any other medical equipment increases the chances of nosocomial transmission using fomites. In manually operated ICUs, frequent visits by healthcare professionals and visitors, further increase the risk of infections, that may further transmit to the community.4,17
Airborne infection isolation rooms with essential negative pressure are not available universally, specially in a resource-constrained environment. The upsurge of critically ill Covid-19 patient might occur rapidly and may result in a state of shock for the management, with the deficient resource available. Low- and middle-income countries face challenges with the availability of ICU beds that are usually deficient. On the other hand, economically well-developed countries might also face challenges with the availability of ICU beds in a sudden outbreak of Covid-19. Any attempts to increase the availability of ICU for the treatment of critically ill patients also demand the availability of basic infrastructure like ventilators, consumables and drugs, which might fall short of supply in the pretext of the pandemic like Covid-19, and presently as well know the world is facing a short supply of ventilators.18
Just increasing the ICU beds might not serve the purpose; this may result in the availability of arms without an army to battle this pandemic, hence availability of skilled staff to manage an ICU is the primary concern. Unequipped ICUs, might result in increased mortality. There is a constant risk of loss of staff to medical illness, quarantine, unprotected exposure to Covid-19, that can affect the psyche and mental composure of the available staff, and during outbreaks like Covid-19, healthcare professionals are generally under mental stress and may land up in depression and anxiety. ICU triage protocols might get tampered if the rate of admission upsurges as the pandemic spreads. Hence in such a scenario, technological advancement in the form of telemedicine/ tele ICUs/e ICUs can help monitor a large number of ICU patients with limited staff and uninterrupted round the clock quality services that cuts through the inherent challenges across ICU setups.4
TELEMEDICINE AND REMOTE SENSING TECHNOLOGY IN PRETEXT OF COVID-19.
Telemedicine with addition of remote sensing technology will limit the amount of exposurea healthcare professional might get exposed during his/her routine Covid19 duties. Using this technology, we can manage unethical admission, proper bed utilisation, drugs and other resources.Looking at the contagiousness of the covid-19 infection it may well be apprehended that even if a slight proportion of population across the globe get infected it would result in thousands of people becoming critically ill which may require management admission in intensive care unit setup. Unfortunately, many countries in the world including developing and underdeveloped countries might not have adequate ICU bed, to tackle sudden upsurge of COVID-19 cases. In this regard the global ICU community must robustly prepare itself for the sudden spike of COVID-19 cases that may over burden and cripple the current functionality of ICU setup across the world. This would be possible if the conventional ICU across the globe would update itself with the modern technological advancement in the form of eICU or TeleICU incorporating artificial intelligence, embedded and remote sensing technology. Such a setup would let us optimize the workflow pattern in advance, enable us to rapidly diagnose and isolate the cases and subsequent clinical management using limited resources. The governing bodies across countries including the administrators and policy makers must join hands with ICU professionals to prepare an extensive and updated plan that would focus towards bed capacity across intensive care unit.5
WHAT IS TELEMEDICINE?
Telemedicine is a science that deals with the exchange of medical information from one site to another using advanced and sophisticated technologies that incorporate artificial intelligence, embedded and remote sensing devices for better healthcare delivery.21 The upsurge of Telemedicine in recent years has changed the clinical practice of all healthcare professionals and workforce which has resulted in changing of professional roles either because of new work flows or active monitoring strategies. eICU enables team members from varied discipline to work closely, it encourages communication among themselves about an individual patient and enables them to work as a team.
CORE COMPONENTS OF AN eICU (TELE-ICU) MODEL.
The first core component of an eICU essentially consists of a:
A multidisciplinary care team consisting of an intensivist, Physician, nurses, physician assistants which are well trained in acute and critical management.
Also, critical care nurses, pharmacist, respiratory therapist, health administrator and an information technologist working congruently and comprehensively towards the management of an individual or a group of patients within the connected chain of eICU.7
Second essential core component of an eICU care revolves around the following values:
Round the clock availability of intensivist to the ICU patients across multiple connected hospitals through a remotely operated, intensivist led multidisciplinary team.
eICU value patient rights with regards to safety, privacy and confidentiality.
eICU encompasses the importance of family care, prevention of risk of exposure and diseases. It encourages collaborative team functioning with sound decision making backed by evidence-based clinical medicine for the betterment of healthcare facilities rendered to the patient.
eICU standardizes the care of management with pre-designed protocols that would serve as a basis for customized management of individual patients based on their disease condition and treatment demands.
eICU enhance the performance of individuals in the multidisciplinary team by cutting of the distractors from their conventional methods of practice which inevitably causes hindrance to better healthcare delivery.
eICU is a need-based concept that emerges from scientific enquires questioning the limitation of conventional clinical practice.4
The third component of eICU encompasses:
Telecommunication gives an enormous opportunity to the healthcare team to reach out to patients from one location to another without geographic limitation. It is also available at the hospital ICU nurses station useful for visual communication with on-site doctors, nurses, and respiratory therapists, and family consultation if needed.8
Teleconferencing uses audio and visual devices which can be used for consultation, enabling therapeutic management across the globe. Virtual rounds can be conducted 3 to 4 times per day. Providing medical expertise wherever needed.9
Clinical Information system holds the database of patient medical history and radio scans, which can be accessed anywhere anytime.
Computerised decision support is an evidence-based science-based on clinical based guidelines and standard protocol improve ICU patient care and improvising cost-benefit decision for minimizing variations in the treatment methods.
Hospital information system improves clinical care & patient safety, Quick & coordinated care. Helps in reducing re-admissions, reducing waiting times and also giving cost-effective treatment.
System databases and Improved Particle Swarm Optimisation (IPSO) that is applied to build a personal physiological signal sensing system based on sensing cloud architecture using cloud equipment technology.4
CHALLENGES OF MANUAL ICUs IN MANAGEMENT OF COVID-19
In a manual ICU setup, critically ill patients are managed manually with the help of healthcare professionals, that need to be present physically for examination, diagnosis, treatment and subsequent interventions. Endotracheal intubations and other aerosol generating procedures need to be conducted in person, increasing the viral load, and chances of infection in an overcrowded ICU facility.
Healthcare professionals managing a manual ICU essentially comprises of an intensivist, an emergency nurse for carrying out tracheal intubation and ventilation support, a physician, a physician assistant and sometimes a pulmonologist to look into the general condition of patient and decide further therapeutic management. A radiologist along with his technician for on-site performance of scan and x-rays, a nurse for drawing blood samples, for insertion and removal of catheters, stabilizing IV lines and for continuous monitoring of vital parameters. Paramedics, ICU technician for looking into logistic of ICU functioning, a pharmacist for dispensing medication, sweepers, helpers, cleaners and allied healthcare professionals to maintain hygiene and sanitation. These entire team needs to work on a shift on and shift off basis, hence at any given point of time, three sets of such dedicated and trained personnel needs to be available for ensuring uninterrupted, round the clock services. Thus a huge number of professionals are required for running one single ICU. Which the government or the healthcare bodies, cannot afford in a pandemic situation like Covid-19.
This means a lot of manual movements in and out of the ICU setup would happen on a daily basis, which can serve as a potential threat for transmission of the viral infection from one site to another.
Managing such a huge team of healthcare and allied professionals, incur huge costs with regards to the renumeration, training, providing for protective equipment's and their resting facilities, which would have a huge impact on the finances of the management in a resource deficient, lockdown scenario.
In a manual ICU setup, repeated investigations, repeated consultations are a norm to gauge the health status of a patient. Thus, frequent interaction between the doctor and patient might render the physicians and associated personnel, to unwarranted exposure of increased viral load, thereby increasing their chances of succumbing to Covid 19.
Training of these healthcare professionals, needs to be carried out regularly, with fresh staff recruiting to supplement the existing ones, in case of a medical emergency, medical leave, post-exposure quarantine and allied challenges of the existing ones. This adds up to the already existing financial burden.
Training sessions in a pandemic scenario are rapid, quick and accurate, that demands quick learning professionals across healthcare. All the medical personnel involved in a manual ICU needs to be trained and streamlined in the protocol and procedure which are pre-designed and standardized in a short period of time. This may increase the chances of grave error while executing their duties due to differences in understanding and retention capabilities of procedural aspects of COVID 19 management. But as these personnel are already under stressful conditions, individual variability of learning is inevitable. And the same concept might be perceived differently by different professionals undergoing training due to subjective variations. This would result in manual errors of monitoring and treatment, which can indirectly add up to the mortality of critically ill ICU patients.
Work stress, burnout, and psychological issues of the working professionals, might hamper their decision making on the go, that might be deleterious for the ICU admitted patients, indirectly contributing to compromised quality of care and mortality.4
ADVANTAGES OF e ICU’s OVER MANUAL ICU’s
In an eICU , the treating physician can manage the patient from a distance place, anywhere in the country, using a monitor which can interact with the patient directly, using telemedicine facility. The aerosol generating procedures and other interventions can be carried out with minimal staff under the supervision of other specialist, hence this helps us to reduce the overcrowding within the ICUs and reduces the risk of transmission of viral infection like Covid-19.
In an e ICU setup, the dedicated team of professionals manage the patients from their respective place of residence or from a distant facility using remote sensing technologies, and it enables them to management more than one ICU, which are interconnected digitally with the help of a very few in house ICU staffs who are well trained in following the necessary protocols and commands. This helps to cut off the barriers of deficient PPEs, and other infrastructural challenges that accompany .10
e ICU's help us to cut down the unnecessary movement in and out of the ICU facility which would prevent unnecessary risks of transmission due to limited movements. It also prevents burnouts of the specialist and allied personnel. These can manage and monitor a large number of patients from their respective place of ease and comfort, enabling swift and intellectual functioning at their best potential in the absence of stress factor.
eICU's enable Multidisciplinary approach of management, as it would enable the specialists and team to frequently interact with each other and make decisions for the best management of the patient in question. This would help to remove human errors and lessen the mortality rates.
Although, setting an e ICU would incur, some additional charges during the phase of installation, with regards to the installation of the biosensors, monitors, remote sensor and telemedicine devices, but once connected with a large number of related ICUs may the setup to be managed by a few competent and technologically advanced set of ICU professionals, that would save on the overall finances in the long run, yet providing the best quality of care with minimum errors in patient management.
The biosensor and other devices, give nearly accurate readings on a continuous basis and the personnel can look into the vitals whenever required, hence unnecessary movement of the treating nurses can also be reduced, protecting them from risk of transmission. And interventions are sorted only when required on an emergency basis as per the decision of the monitoring specialist.
The team of dedicated staff for managing eICU ’s can undergo training in the beginning and once well versed, they can carry out the functions without any difficulty. And then can train the incoming set of new personnel as necessity demands. Hence ongoing training costs and infrastructural demands could be taken care of quickly by this method of functioning.
eICU ’s eliminated the barrier of repeated in person consultation, because in this set up, the treatment physician or any other personnel can look at the vital parameters or speak to the patients as an when required, from their place of convenience. This would enable personalized quality care and will also maintain confidentiality, ethics and professional conduct.
eICU indirectly removes a lot of psychological stress on the healthcare professionals, working in a highly risky environment, by enabling them to function from their location of comfort and intervene in person, only when required. This substantially eases the barriers among the doctor and their family lives, while delivery quality of care on a larger perspective.11
HOW DOES eICU/ TeleICU FUNCTION
The functioning protocol of an e ICU is depicted in Fig.1, which shows the inherent procedures and algorithms involved. On one end is the designated ICU with beds and patients and necessary telemedicine devices involved, Every patient is tagged with an identification code that the networking clients would identify, which would then route using internet or router facility to the server devices like the mobile phones, monitors etc. these are accessible by the team of qualified professionals at any point of time, and at any place. Hence, using this protocol, a physician or an associated healthcare professional can directly interact with the designated patient using the monitor as an interface and carry out the necessary consultations.12
DISADVANTAGES OF eICU
Although installing an eICU setup proves beneficial in the long run but it could incur substantially higher cost for installation of equipment’s, establishment of connectivity line router, biosensor devices, network operating cabins, remote sensing devices and training facilities that may not be feasible in a wider perspective specially in under developed nation.
For smooth functioning of eICU continues power supply, dedicated and ultra-fast Internet or LAN connectivity, intact functioning hardware and software’s are mandatory, any breech in this algorithm due to machine malfunction or interruption cause by natural calamities might disrupt the entire operating apparatus posing a major risk on the delivery healthcare in a critical ICU specially in times of wide spread pandemic like covid 19 unless a backup apparatus is in place.13
Many of the healthcare professional might not be akin to newer technological advancement and might prefer physical touch and heal strategy in such a scenario the entire essence of eICU is lost.
For the country’s healthcare system to revolutionize, needs to be a balance amongst the number of existing trained doctors to treat patients in eICU setup and for technological advances to offer treatment options.
If a healthcare professional is situated in a high security zone with jammers and other devices installed that interferes with the data speed and connectivity. Smooth delivery of critical services might be jeopardy.
High profile data of patients like politicians, celebrities can be hacked for commercial exploitation.
Though eICU is a revolution in patient care, it cannot exchange the human element in treatment.14
DISCUSSION
The concept of e ICU's although established in some developed and developing countries across the world for managing critical care illnesses by skilled staff from the ease of their home, hasn't gained momentum on a broader scale. Reasons for this could be multi-pronged, be it the challenges related to infrastructure like installation of technologically advanced equipment’s containing Biosensing devices, Tele monitor, Router services, Embedded apps or such other gadgets that forms part of eICU functioning, or the deficiency of training or willingness to change from conventional patient management protocols among the skilled staffs and clinicians.
In a pandemic situation like Covid-19, where chances of contracting the illness is pretty high due to highly contagious nature of the virus, where the infection among healthcare workers are increasing on a daily basis due to repeated exposure to Covid-19 patients, where development of complications require ICU management on a large scale in countries like India, Russia, China etc, where the deficiency of PPE and staff is becoming an emerging trend, where treatment costs in private setup are shooting sky-high, most of which is consumed for procuring PPEs and other ICU gadgets for repeated patient interaction to address the emergence and monitor their prognosis in a Covid-19 crisis.
eICU’s with their interconnect chain of other ICUs would come to rescue the healthcare system, which can manage a vast majority of ICU admitted patients through their interconnected network of eICUs through the concept of Telemedicine based on Artificial Intelligence and Embedded technology systems. A dedicated, well trained and sophisticated small team of Technically expert intensivist, Physician and few other in-house staff can manage and interact with every individual through their respective monitor and track their vitals, other parameters from the ease of their home. This could prevent undue exposure of Healthcare professionals to the risk of succumbing to Covid-19, make it feasible to handle large group of patients with individualized care and benefit the infrastructure and economy in the long run. Although implementing this technology may face little challenges with procuring advanced gadgets, recruiting and training staff, availability of skilled technicians and initial installation cost, long-term prospects with management of Covid-19 and allied emergencies would prove beneficial. The Union and state governments must take special interest in updating the existing ICUs and converting them into eICU's on a large scale through implementation of nationwide programmes, encouraging public private partnership models to come forward and execute these initiatives. This would treat many patients and prevent intellectual resources from unduly getting infected and losing their lives.
CONCLUSION
Telemedicine is rather a debatable concept, but in view of the current crisis situation of Covid-19 pandemic, it appears to be the modality of choice. It's a tool that will enhance the moral delivery of health care. Telemedicine was a bystander of the past, which could be the new hope of future in the segment of essential healthcare delivery with decreased risk of exposure and infection. The stakeholders of medical fraternity must ensure that no harm is caused accidentally or as a result of failure of such facilities. The speedy growth of medical informatics and secondary technologies has expanded the boundaries of critical care medicine. The current healthcare system's current problem is the increasing demand for physician services, and therefore, the growing need for cost suppression will become more complex in future. The e ICU/ tele-ICU model for COVID19 would present a viable and safe means for providing high-quality care to underserved communities. eICU/Tele-ICU’s would see substantial growth in width and impact in the future years and will bring a value proposition in the long run. Although, the standard of care, physical touch, consent etc, remains of concern, but the benefits in high risk pandemics is multipronged.Hence the government, regulatory bodies and healthcare management must give a deep thought on revolutionizing age-old ICU models to technologically advanced eICU's/ Tele-ICU's that may cater to a larger population with limited intellectual resources in a crisis like COVID-19 pandemic.
ACKNOWLEDGEMENTS:
We would like to thank Dr. Surendra Naik, MD (Internal Medicine), Dr. HarishH. S, Ophthalmologist Delhi and Dr.M.K. Srinivas, IRMS, Bangalore, for reviewing the article and giving opinions, comments and corrections as appropriate. We extend our thanks to Dr. B. Devanand, Director, VIMS, Ballari, Dr. D. Krishnaswamy, Principal, VIMS, Ballari, Dr. J. Mariraj, Medical Superintendent, VIMS, Ballari, Dr.Y.Vishwanath Professor, Department of Pharmacology, VIMS, Ballari, Dr. Sushil Kumar Varma, Prof & HOD, Department of Pharmacology, MGIMS, Sevagram, for constantly encouraging us to contribute back to medical fraternity and other Faculties of Department of Pharmacology, VIMS, Ballari for their encouragement.
We acknowledge the immense help received from the scholars whose articles are cited and included in references of this manuscript. We are also grateful to authors / editors / publishers of all those articles, journals and books from where the literature for this article has been reviewed and discussed.
CONFLICT OF INTEREST
The authors involved in the current study does not declare any competing conflict of interest.
FUNDING AND SPONSORSHIP
No fund or sponsorship in any form was obtained from any organisation for carrying out this research work.
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Radiance Research AcademyInternational Journal of Current Research and Review2231-21960975-52411213EnglishN2020July6HealthcareMorphometric Study of Plantaris Muscle in South Indian Population and its Clinical Importance
English4650Rahul JainEnglish Radhika P.M.English Shailaja ShettyEnglishBackground: The plantaris has a small belly with a thin slender tendon in the posterior compartment of leg. It’s a vestigial muscle which has gained importance because of its use in tendon grafting. It arises from lateral supracondylar ridge of femur and gets inserted into tendoachillis. It is innervated by tibial nerve and contributes in flexion of knee joint and plantar flexion of the ankle.
Aim: The aim of study is to determine origin, insertion length of the muscle belly, length of the tendon inside the muscle belly, width of the tendon and total length of the tendon of plantaris muscle in south Indian population.
Materials and Method: The present study was carried out on 50 lower extremities from formalin-fixed cadavers irrespective of age, sex and race in the Department of Anatomy, M.S.Ramaiah Medical College. Details of the morphometric measurements of plantaris muscle such as length of the muscle belly, length of the tendon inside the muscle belly, width of the tendon and total length of the tendon, and anatomical variations were noted and measured with a digital vernier caliper, appropriate photographs were taken and results were tabulated after statistical analysis..
Results: In present study, frequency of plantaris muscle is 88.46% in left and 91.66% in right . Themean length of muscle belly was 9.444cm and mean muscle belly width was 1.944cm and total tendon length was 38.028cm and width of tendon was 0.3549cm.
Conclusion: The knowledge of morphometric measurements of plantaris muscle is of importance to radiologists, physiotherapists, orthopaedicians, plastic surgeons, clinicians because of use of muscle tendon in reconstructions, diagnosing muscle tears, MRI intepretation, repair of Atrioventricular valves and muscle injuries.
EnglishPlantaris, Morphometry, Tendon graftingIntroduction-
Plantaris is a small muscle with short belly and a long thin tendon present in the posterior compartment of the leg and soleus and gastrocnemius. It originates from lower part of the lateral supracondylar line and the oblique popliteal ligament and inserts commonly into posterior surface of the calcaneum. It is innervated by tibial nerve which is a branch of sciatic nerve. Its actions mainly include plantar flexion in the posterior compartment of the leg, along with the gastrosoleus1. Plantaris even though a vestigial muscle, is rich in proprioceptive fibres2. .As reported in literature it may be absent in 7-20% cases3; sometimes, it may be appears as dual heads. Besides its minor contribution to mobility, it still has wide clinical and diagnostic importance.
In a study done by Nayak Sr et al.., plantaris muscle was classified into 3 types depending on origin. Type I-arising from Lateral supracondylar ridge,capsule of knee joint and lateral head of gastrocnemius was seen in 73.07% cases, In Type II origin is from capsule of knee joint and the lateral head of gastrocnemius in 5.76% cases, Type III origin is from Lateral supracondylar ridge, capsule of knee joint, lateral head of gastrocnemius and fibular collateral ligament in 13.46% cases4.
The plantaris was also classified based on types of insertion which were, Type I-insertion to the flexor retinaculum of the foot in 28% of cases, Type II-insertion independently to the calcaneum in 36.53% cases, Type III-insertion to the tendocalcaneus at various levels in 26.92% cases4.
In a study done by Nazeer et al.., plantaris muscle insertion were classified into 5 types described Type I-insertion to calcaneum medial to Achilles tendon, Type II-insertion as Fan shaped expansion superficial to the Achilles tendon, Type III-insertion as Fan shaped expansion deep to Achilles tendon, Type IV-insertion as Fan shaped expansion deep to Achilles tendon and flexor retinaculum, Type V insertion with Achillis tendon to the calcaneum5.
In hand surgeries early mobilization is keystone for good outcome, on contrary, early mobilization may rupture the repair at either end of graft. It has been recently published in a article using plantaris with a bone peg as a secondary reconstruction source, since bone to bone attachment occurs quicker than bone to tendon grafts; therefore, this benefits post operative movements and limits adhesions warranting early recovery6-8.
The study aims to determine muscle belly, length of the tendon inside the muscle belly, width of the tendon, and total length of the tendon of plantaris muscle in South Indian population. The tendon of the plantaris muscle can be used for reconstruction of hand tendons, Reconstruction of lateral ankle ligament, Repairs of atrioventricular valves9.
The study is important for physiotherapists, plastic surgeons performing tendon transfer operations, clinicians diagnosing muscle tears and radiologists interpreting MRI scans10.
MATERIAL AND METHODS
The present study was carried out on 50 lower extremities from formalin-fixed cadavers irrespective of age, sex and race in the Department of Anatomy, M.S.Ramaiah Medical College. Dissection of the posterior compartment of leg and popliteal fossa was done and origin and insertion of plantaris were identified. Each specimen was marked and was given number. Details of the morphometric measurements of plantaris muscle such as length of the muscle belly, length of the tendon inside the muscle belly, width of the tendon and total length of the tendon, and anatomical variations were noted and measured with a digital vernier caliper, appropriate photographs were taken and results were tabulated after statistical analysis.
RESULTS
The plantaris muscle was dissected in 50 limbs. Thestatistical analysis was carried out and tabulated. The frequency of presence and absence of plantaris muscle was tabulated in table 1 and fig 1. In the present study, three Types of origin and five types of insertion were tabulated(table 2 and 3). The mean length, width of plantaris muscle and tendon were tabulated.(table 4). In one specimen the plantaris had dual origin (fig 2).
DISCUSSION
Plantaris muscle is considered as vestigial because of its slender tendon and has a minor contribution to the gastrocnemius and soleus muscle of the posterior compartment with which it has been associated. The plantaris joins with triceps surae and plantar flexes the foot through the Achillis tendon. There is growing evidence which suggests, that each of the three muscle has a unique attribute to the overall function of this important muscle group.
The remarkably short and slender plantaris muscle with its long slender tendon serves a proprioceptive function that provides a kinesthetic sense of limb position and muscle contraction. The whole concept of vestigial or functionless muscles is that unused muscles quickly degenerate. It is unlikely that any muscle that was virtually unused for the lifetime of an individual (to say nothing of generations of individuals over millions of years) would remain as healthy muscle tissue2.
The results of the present study were compared with other previous study and tabulated (table 5, 6, 7). In the present study, frequency of absence of plantaris was found to more when compared to other studies. The frequency of insertion of plantaris muscle to bone was seen. This can help the surgeons make a decision for use of plantaris with a bone peg. It was seen that the plantaris is attached to the calcaneum in 77.7% making it an ideal source for tendon grafting.
Clinically, plantaris tendon is an ideal source for soft tissue augmentation for ligament reconstruction or tendon repair. The plantaris tendon has high tensile strength with structured collagen characteristic of physiologic tendons. Harvest of plantaris tendon rarely creates appreciable donor site morbidity. Plantaris tendon has highest tensile strength (94 N/MM3)11. It is also considered as ideal graft due to location in sterile field for every foot and ankle procedure. No arteries, nerves, and veins are present between soleus and gastrocnemius, making it even easier for harvesting12.
Ultrasound is useful in identifying the presence of a plantaris tendon and has high specificity. MRI is used to evaluate an injury to an ankle ligament, it can also be used in identifying presence of an ipsilateral plantaris tendon that may be used for tissue augmentation.10
Plantaris tendon can be used in AV valve repair. The mitral valve repair is better than mitral valve replacement because prosthetic ring annuloplasty is associated with chronic anticoagulation, suboptimal hemodynamics, and potential infectious complications which can be avoided using plantaris tendon. Normal left ventricular geometry is maintained by retaining the native mitral valve apparatus and annuloplasty can be performed by tendon tissue due to its smooth surface. Splitting or lateral stretching stimulates collagenous adhesions that in theory can impart superior dynamics through an anatomic restoration that surpasses a synthetic restoration. The easy availability of plantaris tendon, in addition, makes it an economic source of material to cover tissue defects after removal of calcified atrioventricular valves, which should contribute plantaris tissue for the particular use in developing countries9.
In the present study, dual origin was noted in 6 specimens and in one specimen it was double head. Dual origin plantaris can sometimes gives way to tibial nerve passing in between the two heads and can cause pain in the lower limb due to compression of nerve while walking between the two heads13.
Conclusion-
Plantaris muscle has a long slender tendon which fuses with superficial fascia of leg, thereby making it vulnerable to injury. The topographical anatomy of plantaris muscle and its resemblance to a nerve should be kept in mind by the surgeons operating on the back of leg. The rupture of tendon is often difficult to diagnose since it is associated with haemorrhage and edema.
. In present study plantaris was absent in 10% of legs which is clinically relevant as plantaris and its tendon have multiple uses in clinical practice. In the present study, morphometric analysis of plantaris was done which is of immense importance to the plastic surgeons performing tendon transfer operations, clinical diagnosing muscle tears and radiologists interpreting MRI scans.
Acknowledgment
Authors acknowledge the immense help received from the scholars whose articles are cited and included in references of this manuscript. The authors are also grateful to authors / editors / publishers of all those articles, journals and books from where the literature for this article has been reviewed and discussed.
Source of Funding : Nil
Conflict of interest : None
Englishhttp://ijcrr.com/abstract.php?article_id=2702http://ijcrr.com/article_html.php?did=27021. Richard L Drake, A Wayne Vogl, Adam W. M. Mitchell. Gray's Anatomy for Students, 1st South Asia ed. New Delhi: Elsevier; 2017:680.
2. David N. Menton. The Plantaris and the Question of Vestigial Muscles in Man. Journal of Creation. 2000; 14(2):50–53
3. Simpson S L, Hertzog M S, Barja R H. The Plantaris Tendon graft: An Ultrasound Study. Journal Hand Surg July 1999;16(4):708-11
4. Nayak SR, Krishnamurthy A, Ramanathan L, Ranade AV, Prabhu LV, Jiji PJ, Rai R, Chettiar GK, Potu BK. Anatomy of Plantaris Muscle: A study in adult Indians. La clinical Terapeutica2010;161(3):249-252.
5.Nazeer Ahmed, Khwaja Nawazuddin Sarwari. Morphological variations and surgical importance of the plantaris muscle in humans. Indian Journal of Fundamental and Applied Life Sciences ISSN 2013; 3(4):342-346
6. Amadio P, An KN, Ejeskar A, Guimbertau, J Claude, Harris S, Savage R, Stewart K,P., Bo Tang J. IFSSH Flexor Tendon Committee report 2014: from the IFSSH Flexor Tendon Committee. J Hand Surg 2005;30B:100–116
7. Amadio PC, Wood MB, Cooney WP 3rd, Bogard SD. Staged Flexor tendon reconstruction in the Fingers and hand. J Hand Surg1988;139 (4): 559–62
8. Bertelli JA, Santos MA, Kechele PR, Rost JR, Tacca CP. Flexor tendon grafting using a plantaris tendon with a fragment of attached bone for fixation to the distal phalanx: a preliminary cohort study. J Hand Surg 2007;32A:1543–1548.
9. Jeffrey H Shuhaiber and Hans H Shuhaiber. Plantaris Tendon Graft for Atrioventricular Valve Repair. Tex Heart Inst J 2003; 30(1):42–4.
10. Andreo A. Spina. The plantaris Muscle: Anatomy, Injury, Imaging and Treatment. Canada: J Can Chiropr Assocjul-Sept 2007; 51(3):158–165
11. Bohnsackm, Surieb, Kirschil et al. Biomechanical properties of commonly used autogeneous transplants in the surgical treatment of chronic lateral ankle instability. Foot Ankle Int 2002;23:661-664.
12.Geert I Pagenstert, Beat hintermann. Proximal Mini-invasive Grafting of Plantaris Tendon. Campbell’s operative orthopaedics. Volume 4,10th edition. Edited by S Terry Canale. St louis:Mosby; 2003:4454-4457.
13. Upasna, Ashwini Kumar. Bicipital origin of Plantaris Muscle – A Case Report. International Journal of Anatomical Variations 2011; 4:177–179
Radiance Research AcademyInternational Journal of Current Research and Review2231-21960975-52411213EnglishN2020July6HealthcareChallenges of Pre-analytical Variables in Conventional Cytogenetics - A University Teaching Hospital Experience
English5155 Vidya JhaEnglish Ajeesh G.A.English Akhil K.S.EnglishIntroduction: Conventional Cytogenetics is an essential tool for the diagnosis of a neoplastic or premalignant condition and provides important prognostic and therapeutic information. The rate of unsuccessful karyotyping in hematological malignancies is reported between 10-20%.
Objective: To analyze the relationship between pre-analytical variables and associated failures with conventional karyotyping in hematological neoplasms.
Material and Methods: 1020 samples with suspected hematological malignancies received in the department of Cytogenetics from January 2018 to December 2019 were included in the study. Pre-analytical variables assessed included time from collection to sample processing, type of sample, diagnosis and sample cellularity. Statistical analysis was performed using Chi-square test to verify associations of variables with karyotyping.
Results: 86 (12%) out of 720 samples that were processed in less than 24 hours of time of collection showed an unsuccessful KT while 57/300 samples (19%) that were processed beyond 24 hours failed to yield any metaphase (p-value 0.003). 31/79 PVB (39%) and 112/941 BM (12%) were unsuccessful (p-value 7 x 103/μl and 119/201 (59%) samples with low cellularity being ≤7 x 103/μl were unsuccessful (p-value EnglishPre-analytical variables, Karyotyping, Cytogenetics, Hematological malignanciesIntroduction
The World Health Organization (WHO) classification of tumors of the hematopoietic and lymphoid tissues incorporates cytogenetic and molecular genetics abnormalities.1
Hematologic neoplasm is listed in the top ten malignancies worldwide and also one of the leading causes of mortality in patients with cancer. Almost 9% of all cancer cases diagnosed in a year are hematological malignancies.2,3 Identification of clonal aberrations yields support in diagnosing malignant/premalignant diseases as well as gives important information regarding prognosis and therapy.4,5 Therefore, conventional cytogenetic analysis is mandatory in the evaluation of suspected acute leukemia. It is one of the essential tools for classification of hematological malignancies, prognostication and treatment.6,7 It is also seen that unsuccessful conventional karyotyping has a prognostic implication in hematological malignancies.8,9,10
The rate of unsuccessful karyotyping in hematological malignancies is reported between 10-20%. Successful karyotyping is affected by number of factors like nature of sample, time to process, collection method, cellularity of sample and processing methods.11 The present study aims to analyze the relationship between pre-analytical variables and associated failures with conventional karyotyping in hematological neoplasms.
Material and methods
The archives of department of Cytogenetics were retrospectively reviewed from January 2018 to December 2019. Of the 4300 cytogenetic case records reviewed over a period of 2 years, 1020 samples of bone marrow and blood with suspected hematological malignancies were received over a period of 2 years. Along with clinical history and examination, peripheral blood counts, marrow morphology and immunophenotyping was done to come to a diagnosis. Molecular tests like JAK2 mutation, Ph chromosome etc. were done, wherever required. Final diagnosis was made based on WHO criteria.1 Bone marrow samples were cultured for 17 and 24 hours without mitogenic agents and harvested following standard protocols.7 The slides were air-dried and stained with G-Banding using Trypsin and Giemsa (GTG-banding). Twenty metaphases were analyzed and karyotypes were described according to the International System for Human Cytogenetic Nomenclature criteria.12
Pre-analytical parameters
The following pre-analytical variables were noted:
Time from sample collection to initiation of processing in lab (more or less than 24 hours)
Material type (bone marrow or peripheral venous blood)
Sample cellularity (>7 or ≤7 x 103/µl)
Patient’s diagnosis (AML. ALL, MDS, MPN, CLL, MDS/MPN)
Statistical analysis was performed using Chi-square test to verify associations of variables with karyotyping. The data were analyzed using IBM SPSS software (Version 21). The level of significance for the statistical tests was 5% (p-value < 0.05).
Results
Out of the 4300 cases received in Cytogenetics lab over a period of 2 years, 1020 samples with hematological malignancies were found. The mean patient age was 46 years (range 1 month – 84 years). There were 612 (60%) males and 408 (40%) females with a male : female ratio of 1.5. The diagnosis of 1020 cases as per the WHO criteria was as follows: myeloproliferative syndrome 338 (33%), acute myeloid leukemia 287 (28%), acute lymphoid leukemia 156 (15%), myelodysplastic syndrome 109 (11%), MDS/MPN 34 (03%) and Others like plasma cell disorder, chronic lymphoid leukemia etc 96 (09%).
Out of the 1020 samples, there were 941 (92%) bone marrow (BM) specimen and 79 (08%) peripheral venous blood (PVB) specimens. 720 (71%) samples had culture set up in less than 24 hours from their time of collection. 819 (80%) samples had cellularity more than 7x103/µl.
143 (14%) samples out of 1020 failed to yield any metaphase on culture that precluded any cytogenetic analysis. The pre-analytical variables associated with unsuccessful or failed karyotype (KT) are shown in table 1. 86 (12%) out of 720 samples that were processed in less than 24 hours of time of collection showed an unsuccessful KT while 57/300 samples (19%) that were processed beyond 24 hours failed to yield any metaphase (p-value 0.003). 31/79 PVB (39%) and 112/941 BM (12%) were unsuccessful (p-value 7 x 103/µl and 119/201 (59%) samples with low cellularity being ≤7 x 103/µl were unsuccessful (p-value Englishhttp://ijcrr.com/abstract.php?article_id=2703http://ijcrr.com/article_html.php?did=2703
Arber DA, Orazi A, Hasserjian R, Thiele J, Borowitz MJ, Le Beau MM, et al. The 2016 revision to the World Health Organization classification of myeloid neoplasms and acute leukemia. Blood 2016; 127: 2391–2405 doi:10.1182/blood-2016-03-643544.
Prakash G, Kaur A, Malhotra P, Khadwal A, Sharma P, Suri V, et al. Current role of genetics in hematologic malignancies. Indian J Helmitol Blood Transfus 2016;32:18-31.
Siegel R, Ward E, Brawley O, Jemal A (2011) Cancer statistics,2011: the impact of eliminating socioeconomic and racial disparities on premature cancer deaths. CA Cancer J Clin 61(4):212–236
Rack, K.A., van den Berg, E., Haferlach, C. et al. European recommendations and quality assurance for cytogenomic analysis of haematological neoplasms. Leukemia 33, 1851–1867 (2019). https://doi.org/10.1038/s41375-019-0378-z
Mitelman F, Johansson B, Mertens F. Mitelman database of chromosome aberrations and gene fusions in cancer. 2018. http://cgap.nci.nih.gov/Chromosomes/Mitelman
Santos MFM, Oliveira FCAC, Kishimoto RK, Borri D, Santos FPS, Campregher PV et al. Pre-analytical parameters associated with unsuccessful karyotyping in myeloid neoplasm: a study of 421 samples. Braz J Med Biol Res. 2019 Feb 14;52(2): e8194. doi: 10.1590/1414-431X20188194.
Haferlach C, Rieder H, Lillington DM, Dastugue N, Hagemeijer A, Harbott J, et al. Proposals for standardized protocols for cytogenetic analyses of acute leukemias, chronic lymphocytic leukemia, chronic myeloid leukemia, chronic myeloproliferative disorders, and myelodysplastic syndromes. Genes Chromosomes Cancer 2007; 46: 494–499, doi:10.1002/gcc.20433.
Medeiros BC, Othus M, Estey EH, Fang M, Appelbaum FR. Unsuccessful diagnostic cytogenetic analysis is a poor prognostic feature in acute myeloid leukaemia. Br J Haematol 2014; 164: 245–250, doi: 10.1111/bjh.12625.
Yang W, Stotler B, Sevilla DW, Emmons FN, Murty VV, Alobeid B, et al. FISH analysis in addition to G-band karyotyping: utility in evaluation of myelodysplastic syndromes? Leuk Res 2010; 34: 420–425, doi: 10.1016/j.leukres.2009.09.013.
Cervera J, Solé F, Haase D, Luño E, Such E, Nomdedeu B, et al. Prognostic impact on survival of an unsuccessful conventional cytogenetic study in patients with myelodysplastic syndromes. In: Leukemia Research 2009; 33: Abstracts of the 10th International symposium on myelodysplastic syndromes, Patras (Greece) 6–9 May 2009. Abstract number: P030.
Watson MS. Quality assurance and quality control in clinical cytogenetics. In: Dracopoli NC, Haines JL, Korf BR, Morton CC, Seidman CE, Seidman JG, Smith DR (Ed), Current Protocols in Human Genetics. New York: John Wiley; 2007. p 8.2.1–8.2.9.
Shaffer LG, Tommerup N ISCN 2005, an international system for human cytogenetic nomenclature (2005), S. Karger AG, Basel (2005) ISBN 3-8055-8019-3.
Hook EB. Exclusion of chromosomal mosaicism: tables of 90%, 95% and 99% confidence limits and comments on use. Am J Hum Genet. 1977;29:94–97.
Mikhail FM, Heerema NA, Rao KW, Burnside RD, Cherry AM, Cooley LD. Section E6.1-6.4 of the ACMG technical standards and guidelines: chromosome studies of neoplastic blood and bone marrow-acquired chromosomal abnormalities. Genet Med 2016; 18: 635–642, doi: 10.1038/gim.2016.50.
Potter AM, Watmore A. Cytogenetics in myeloid leukaemia. In: Rooney DE and Czepulkowski BH (Ed). Human Cytogenetics: A Practical Approach. Volume 2: Malignancy and Acquired Abnormalities. Second edition. Oxford: IRL Press at Oxford University Press, 1992. p28.
Cherry AM, Slovak ML, Campbell LJ, Chun K, Eclache V, Haase D, et al. Will a peripheral blood (PB) sample yield the same diagnostic and prognostic cytogenetic data as the concomitant bone marrow (BM) in myelodysplasia? Leuk Res. 2012;36:832–40.
Hussein K, Ketterling RP, Hulshizer RL, Kuffel DG, Wiktor AE, Hanson CA, et al. Peripheral blood cytogenetic studies in hematological neoplasms: predictors of obtaining metaphases for analysis. Eur J Haematol 2008; 80: 318–321, doi: 10.1111/j.1600-0609.2007.01021.x.
Lozynskyy RY, Lozynska MR, Hontar YV, Huleyuk NL, Maslyak ZV, Novak VL. Study of cytogenetic abnormalities in G-CSF stimulated peripheral blood cells and non-stimulated bone marrow cells of patients with myelofibrosis. Exp Oncol 2016; 38: 40–44.
Gersen SL and Keagle MB (Ed). The principles of clinical cytogenetics. Second edition. New Jersey: Humana Press, 2005, doi: 10.1385/1592598331.
Stevens-Kroef MJ, Olde Weghuis D, ElIdrissi-Zaynoun N, Van der Reijden B, Cremers EMP, Alhan C, et al. Genomic array as compared to karyotyping in myelodysplastic syndromes in a prospective clinical trial. Genes Chromosomes Cancer 2017; 56: 524–534, doi: 10.1002/gcc.22455.
Arsham MS, Barch MJ, Lawce HJ. The AGT Cytogenetics Laboratory Manual. Fourth edition. Hoboken, New Jersey: Wiley-Blackwell, 2017, doi: 10.1002/9781119061199.
Döhner H, Estey E, Grimwade D, Amadori S, Appelbaum F, et al. Diagnosis and management of AML in adults: 2017 ELN recommendations from an international expert panel. Blood. 2017;129(4):424-447.
Swansbury J. Cytogenetic studies in hematologic malignancies: an overview. In: Swansbury J (Ed). Cancer Cytogenetics: methods and protocols. First edition. New Jersey: Humana press, 2003. p 13–17.
Radiance Research AcademyInternational Journal of Current Research and Review2231-21960975-52411213EnglishN2020July6HealthcareThe Trend of COVID-19 at Bengaluru: Prediction to Continue the Better Epidemic Management
English5660Kannamani RamasamyEnglish S. JayakumarEnglishAim: The primary objective of this study is to understand the current situation of COVID-19 at Bangalore city and predict the future state, which will help for better management.
Methods: Data from BBMP and Karnataka's government from 1 April to 12 June 2020 used to calculate the prediction. We have used FORECAST.ETS function in Microsoft EXCEL to predict the future number of COVID-19 cases for Bangalore city.
Results: Based on the prediction analysis, the number of cases at Bangalore may reach 3240 by the end of Aug 2020. The percentage of positive cases at Bangalore from the total samples tested across Karnataka may reach up to 0.6 %. Death count due to COID-19 may touch at 80. Overall, the prediction appears that the status of the COVID-19 may continue to be good with some additions.
Conclusion: Bangalore is doing well with COVID-19 management. However, the situation may change at the point of time due to various contributors. Proactive approaches, as mentioned in the recommendations section, is much critical to managing the pandemic situation.
EnglishBangalore, COVID-19, Coronavirus, BBMP, Trend, PredictionIntroduction
Coronaviruses are a large family of viruses which may cause sickness in animals or humans. Several Coronaviruses are identified in humans to cause respiratory infections ranging from the typical cold to severe diseases. This new virus COVID-19 and disease were identified in Wuhan, China, in December 2019. The common indications of COVID-19 are fever, dry cough and tiredness. Some patients may have aches and pains, sore throat nasal congestion, sore throat or diarrhoea and runny nose. These symptoms are usually mild and improve gradually. Some people become infected but don't show any signs and they appear to be well. Aged people and those going through medical problems like high blood pressure, cardiovascular issues or diabetes, are more likely to grow serious illnesses. People who have the indications of dry cough, fever, and difficulty in breathing must consult with the medical professional1. Globally, India is in 4th place with 333,008 cumulative positive cases as on 15 June 2020, next to America (2,162,228), Brazil (867,882) and Russia (528,964)2. In India, Karnataka is in 10th place with the 7213 (as of 15 June 2020) confirmed cases3. Within Karnataka state, Bangalore is in 4th place with 725 cases (as of 15 June 2020) next to Udupi, Kalaburagi and Yadagiri districts4.
Bangalore city – Overview
Bangalore city is one of the fastest emerging cities in India and capital for Karnataka state. The Bangalore city is the fifth-largest city across the country. Bangalore city called ‘Garden city ‘of India due to the huge number of trees and plentiful greenery. Bengaluru city is also called as “Silicon Valley of India” for the development of IT and ITES sectors in India. Bangalore renamed as “Bengaluru” in 2014. Various Indian technological organizations such as Indian satellite research organizations, Infosys Limited, Wipro, and Hindustan aeronautical limited are headquartered in the city. A demographically diverse city and has highly educated workforces in the world. Bengaluru is a place where multiple educational and research institutions located such as Indian Institute of Bangalore, Indian Institute of Science, National Institute of Advanced Studies, Tata Institute of Fundamental Research, Institute for Social and Economic Change, International Institute of Information Technology Bangalore, National Institute of Design, R & D Campus, National Law School of India University and The National Institute of Mental Health and Neuro-Sciences. Bangalore is located at 12.590 north latitude and 77.570 east longitude and positioned at an altitude of nine hundred and twenty meters above sea level. Bangalore city has more than 650 Indian and multinational companies. Bangalore is contributing 35% of India‘s software exports5.
Motivation
Bangalore is the silicon valley of India. The city is well connected with all other major cities in India. On 9 March 2020, the first COVID-19 case identified at Bangalore. Bangalore is appropriately connected with the International airport with huge visitors from multiple nations and cities. As of 15 June, the city has 725 COVID-19 confirmed cases. For a population of 1.3 crores, the number of cases is pretty less (0.005%). Though neighbouring states like Tamilnadu and Maharashtra affected severely, Bangalore can maintain the confirmed cases at a low level. This exciting pattern is making us study about the COVID-19 status at Bangalore.
Present COVID-19 situation at Bangalore
Figure 1 shows the trend of COVID-19 confirmed cases in India, Karnataka and Bangalore city, as on 13 June 2020. The first case in the state identified on 8 March 2020.
Figure 2 shows the number of COVID-19 cases for all the districts in the Karnataka as on 13 June 2020. Bangalore Urban is in 4th place in the state next to Kalburgi, Yadagiri and Udupi districts. As of today (15 June 2020), there are 725 confirmed cases in the Bangalore city. The city is able to maintain the lower count with many initiatives11 by the authorities. Some of them are : Around 140000 people involved in international travelling were screened and they have kept under monitoring. Also, their associate contacts were kept under observation. Coordination between the civic agency, health and home departments was effective, which helped maintain the numbers at minimal. Citizens of Bengaluru are responsible, managing the social distancing and wears a mask. Bruhat Bengaluru Mahanagara Palike’smapping of containment zones and predictive modelling are vital factors for success. Bruhat Bengaluru Mahanagara Palike had taken the police department's help and protected health workers, so they were able to perform their duties11.
Figure 3 shows the trend and the number of cases during each lockdown and also after lifting the lockdown. The first case in the state identified on 8 March. During the first lockdown (1.0), there were 32 confirmed cases in Bangalore. During the second lockdown (2.0), there were 71 cases in total. During the 3rd lockdown(3.0), the number of cumulative confirmed cases were 153. There were 239 cases during 4th lockdown(4.0). During 5th lockdown(5.0), the aggregate number of confirmed cases was 358 in Bangalore city. After lifting the lockdown, as of 15 June, the number of confirmed cases increased to 725 from 358.
Figure 4 shows the number of confirmed cases in Bangalore from 1 April to 14 May, where we can see an increasing trend. Figure 5 shows the number of confirmed cases in Bangalore from 14 May to 13 June 2020. Figure 6 represents the trend of percentage of confirmed cases at Bangalore from the number of total samples tested on that particular day across Karnataka state. Figure 7 indicates the direction ofCOVID-19 death cases at Bangalore city from 19 April (reported 4 deaths) to 13 June 2020 (34 cumulative death cases).
Forecasting technique used
In this paper, we have used FORECAST.ETS function in Microsoft EXCEL to predict the future number of COVID-19 cases for Bangalore city. The Excel8 Forecast.Ets function uses an exponential smoothing algorithm to predict a future value on a timeline, based on a series of existing values. From 1 April 2020 till 13 June 2020, used as a current data. Prediction analysis calculation made from 14 June 2020 to 31 August 2020. Prediction analysis calculated for around 75 days. Calculating prediction analysis for more days (more than three months) may lead to deviation as there may be various factors that would change in the long duration. However, with 75 days duration, lower and upper bound should be able to help us to cover the variations.
Prediction of COVID-19 for Bangalore
Prediction for Positive cases
This prediction applies from 14 June to 31 August 2020. In figure 8, bluelines are indicating the past trend and orange lines are showing the future trend. The thin lines above the orange indicate the upper limit, and the range within orange lines indicates the lower limit of the forecasting. With 95% confidence level, the prediction may vary from lower to upper numbers. Figure 9, too representing the forecasting; however, it is presented for clear visibility by using the weekly data.
Prediction of Samples (positive cases) from the total test
In figure 10, bluelines are indicating the past trend and orange lines are showing the future trend. Currently (as on 13 June 2020), it is at 0.34 % and in the future (as of 31 August 2020), it may go up to 0.60 %.
3. Prediction of Number of Death cases
As of 12 June 2020, the number of death cases declared by the authorities of Bangalore city is 30. Based on the prediction analysis, the number of death count may go up to 59 by 31 August 2020 (Figure 11). In the worst scenario, it may reach up to 79 (refer upper bound in the figure, yellow colour) and with better measures, it can be controlled at 39 (refer lower bound in the figure, grey colour).
Discussion and Interpretation
Mumbai, which is the capital of Maharashtra, is profoundly affected by an enormous number of COVID-19 case. Chennai which is the capital of another neighbour state for Karnataka, also affected severely12. The first case of Karnataka found on 8 March 2020 and as on 15 June 2020, the number of positive cases is 7213. The number of positive cases in Bangalore is around 700 (figure 5). Though there are a massive number of IT companies, other industries and exposure to international travel, maintaining this number at Bangalore is appreciated. One side, it is essential to know that many precaution measures (discussed in the section named “Present COVID-19 situation at Bangalore, reference no 11) have been taken by the government of Karnataka and BBMP at Bangalore city to maintain and control the spread. While we are happy to see the low number of positive cases, if the number of samples testing goes high, it may reveal even more positive cases. 4020 samples tested per million across Karnataka9, as of 29 May 2020. Testing is the crucial element to control the spread. It is important to note that the World Health Organization sent an advisory to all countries in March to conduct more test. The more tests we do (5139 tests conducted per million at Bangalore, as of 21 June 2020), the easier it is to track the spread of the virus and reduce transmission. Many countries followed the advice, which was resulted in better outcome10. Another possible reason for low numbers of positive cases at Bangalore may be due to the educated crowd in the city. A considerable number of people are working in IT, ITES, education, and other industries where they can work from home. Hence, there are no physical contacts which helped for better social distancing.
Another side, through the cumulative confirmed cases, the situation is under control at the Bangalore city. In the past one week, the counts are kept on increasing. Till 14 May, the number of cases is 200 (figure 4) and from 15 May to 15 June, 500 cases are added within a month (figure 5). The percentage of positive cases at Bangalore from the total samples tested across Karnataka vary from 0.1 to 0.3 on average (figure 6). On 19 April, 4 death cases reported and on 12 June, the cumulative death count was 30. (figure 7).From the lockdown 0 to 4, the number of confirmed cases was 358. After unlocking, the number of cumulative cases reached 700. This pattern raises another question of whether the unlocking played a massive role in increasing the confirmed cases(figure 3). We have used the FORECASTING ETS option to predict the future numbers for Bangalore city. As of 31 August 2020, the expected number of positive cases would be 3239 (figure 9) with a 95% confidence level. Based on the conditions, the number of cases may vary, which is indicated as lower bound (between orange lines) and upper bound (Above orange lines) (figure 9). The percentage of positive cases at Bangalore from the sample tested across Karnataka may go up to 0.6 (figure 10); it may vary between 0.4 to 0.6 on an average. Currently, most of the days, it ranges from 0.1 to around 0.3 on an average (figure 10). As of 31 August, the number of death cases in the city would be around 59. In the worst situation, it may go up to 80 (indicated as upper bound) and it would be approximately 40 mentioned as lower bound if everything goes well and the situation is under better control. (figure 11).
Recommendations:
Current efforts by the government of Karnataka and BBMP continue to maintain the low number of positive cases concerning COVID-19.
The number of testing per million to be increased for better control and containment.
Entry process and security measures to be strengthened at the borders of Bangalore city.
BBMP and Government of Karnataka to advise the IT, ITES industries to continue the work from home for a few more months.
Until there is a situation that can give the officials, medical experts, and citizens confidence, authorities should not allow educational institutes to operate.
Conclusion:
Performing well is appreciated; however, continuous performance is essential, which is not easy. Possibly with the current measures and additionally, the recommendations mentioned in the discussion and recommendations section, Bangalore can maintain the COVID-19 positive cases at a low level. But it does not mean that it will continue forever. Disaster may knock the door at any time. Preparedness for the bad situation will help to react to the situation with the proactive plans. An individual or administrator can succeed only with the proper forecasting about the future. It is advisable to calculate the forecasted numbers time to time and plan accordingly for city’s epidemic management.
Acknowledgement
Our sincere and heartfelt thanks to all the authors, Bruhat Bengaluru Mahanagara Palike, Ministry of health- Government of Karnataka and Ministry of health - Government of India whose articles/reports/data are cited and included in references to this manuscript.
Conflict of interest - The authors declare that there is no conflict of interest.
Financial support – No funding.
Englishhttp://ijcrr.com/abstract.php?article_id=2704http://ijcrr.com/article_html.php?did=2704
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Rate of COVID-19 testing in most impacted countries worldwide as of 15 June, 2020, https://www.statista.com/statistics/1104645/covid19-testing-rate-select-countries-worldwide/ , accessed on 15 June 2020.
How Bengaluru kept its coronavirus count low, https://timesofindia.indiatimes.com/city/bengaluru/how-bengaluru-kept-its-coronavirus-count-low/articleshow/76240490.cms , accessed on 15 June 2020.
12. Kannamani Ramasamy, S. Jayakumar, Govindasamy Chinnu. COVID-19 Situation at Chennai City – Forecasting for the Better Pandemic Management International Journal of Current Research and Review. Vol 12 Issue 12, June 2020, 37-47, doi: http://dx.doi.org/10.31782/IJCRR.2020.12128
Radiance Research AcademyInternational Journal of Current Research and Review2231-21960975-52411213EnglishN2020July6HealthcareRole of Vitamin-C Supplementation in Type II Diabetes Mellitus
English6164Suraj P WaghEnglish Shweta P BhagatEnglish Nandkishor BankarEnglish Karan JainEnglishIntroduction: Diabetes Mellitus is affected by genetic and environmental influences and is characterized by impaired insulin secretion, insulin resistance and chronic hyperglycemia. Vitamin-C levels are typically small for T2DM patients because blood glucose may compete with Vitamin-C for cell absorption due to its structural similarity to the oxidized form and increased oxidant stress may deplete antioxidant stocks. Vitamin-C, an essential micronutrient with potent antioxidant properties, can protect important biomolecules from oxidation by participating in oxidation-reduction reactions and is readily oxidized to dehydroascorbic acid, which is then reduced to ascorbate again.
Material and Methods: In this prospective study, 412 patients were included who were diagnosed with T2DM and were randomly divided into two groups of 206 each (the study group and control group). Standard methods for evaluating glycated hemoglobin (HbA1c) have been used in ETDA(Ethylenediaminetetraacetic acid) blood. Glucose for fasting was measured in blood. Vitamin-C and placebo were administered to patients for three weeks at a time. During follow up, patients were advised to bring unused drugs and containers. All patients had their regular dietary pattern preserved through constraining their intake of foods, which are rich in Vitamin-C.
Results: There were total 206 patients were included as study group and control group, respectively. 123 were males among 206 patients in Vitamin-C group while 83 were females. In control group 120 were males and 86 were females among 206 controls. The mean age of cases in Vitamin-C group is noted to be 45.77 ± 7.66 while in control group it is 43.33 ± 5.64. The mean post meal blood sugar has significantly decreased in cases administered with Vitamin-C compared to controls. In group, B saw a significant decrease in fasting blood sugar levels and HbA1c. Plasma Vitamin-C levels had a significant increase in study group.
Conclusion: Vitamin-C supplementation can substantially reduce level of HbA1c as well as blood glucose in T2DM patients.
EnglishHbA1c, Vit-c, T2DM, DM, Vitamin-CINTRODUCTION:
Diabetes is one of the fastest growing challenges in 21st century. The number of adults living with diabetes has tripled in last 20 years. According to international diabetes federation diabetes Atlas, it has been noted that 463 million adults in age group 20 to 79 years are living with diabetes[i]. At least 90% of cases of diabetes are accounted for T2DM among all cases with disease.
Due to micro vascular complication like nephropathy, neuropathy, retinopathy and macro vascular complications like stroke, peripheral vascular disease and myocardial infarction Diabetes Mellitus is one of the major risk factors associated with morbidity and mortality[ii]. It is shown that free radical-mediated pathology plays an important role in Diabetes Mellitus[iii],[iv].
Nutrients act as an important source in disease prevention and health care. Nutrients with vitamins are very important for cardiovascular health (i.e. vitamin B1), nerve function (i.e. vitamin B6 and vitamin B12), development of red blood cells (vitamin B12 and folate), coagulation (vitamin K) among other functions[v]. Decreased metabolic rates have been shown to correlate with an elevated body mass index (BMI) and increased obesity prevalence[vi]
Vitamin-C acts as an antioxidant. The intrinsic relation between Vitamin-C and glucose is of concern to diabetes[vii]. Oxidant stress can lead to disrupted glucose metabolism and hyperglycemia[viii]. Vitamin-C is an essential micronutrient with powerful antioxidant properties which can prevent essential biological molecules from oxidation by engaging in oxidation reduction reactions and therefore is easily oxidized to dehydroascorbic acid, which then in fact reduces back to ascorbate. Vitamin-C occurs naturally in fruits and vegetables and is also used as an additive to foods or drinks. Vitamin-C is water soluble and therefore has a comparatively short half-life in body. Regular and sufficient consumption of Vitamin-C is needed to prevent deficiency due to fast renal excretion[ix].
The amounts of Vitamin-C in T2DM patients are relatively low as blood sugar level may compete with Vitamin-C for absorption into cells due to the structural resemblance to oxidized type, and elevated oxidant stress decrease antioxidant stores[]. Vitamin-C supplementation has improved blood glucose levels and many studies even reported glycosylated hemoglobin (HbA1c).
MATERIAL AND METHODS:
In this prospective study setting, 412 T2DM were included, which were divided into two groups. This research was conducted in conjunction with Dept. of Biochemistry, Jawaharlal Nehru Medical College, Datta Meghe Institute of Medical Sciences, Wardha & Dept. of General Medicine, Zydus Medical College and Hospital for over 1 year. 206 patients were randomly allocated as cases and controls. Cases were administered with Vitamin-C. Block randomization technique was used for Vitamin-C and control blocks.
Inclusion criteria: Patients visiting outpatient department having blood glucose level ranging from 126 to 250mg/dL have been included in the study.
Exclusion criteria: Patients of inflammatory bowel disease medical history and patients who have had prior resection of the intestines were included from study.
Data on physical activity and demography was collected at start of the study along with body mass index (BMI) of patients, circumference of waist and hip.
Computation of BMI was done by taking ratio of weight in kilograms to height in square meters. After meals, venous blood samples were obtained 12 hours or 12 hours fasting. In EDTA blood glycated haemoglobin (HbA1c) has been calculated using standard methods. Fasting glucose has been measured through blood samples collected by oxalate fluoride tube. Vitamin-C concentration of extracted samples was calculated. During the study, patients received their regular dietary regimen while still limiting their consumption of food rich in Vitamin-C.
Mean ± standard deviation (SD) has been used to express results. Differences in groups were analyzed by using unpaired or paired t-test. Based on the distribution of data, relationship between variables was measured by Pearson’s or Spearman’s correlation coefficient. Chi-square test analysis was performed to determine demographic data. Results were considered statistically significant at p-value below 0.05.
RESULTS:
Patients were randomly assigned to groups with 206 patients in each group mentioned in the table above. There were 123 males and 83 females in group administered with Vitamin-C whereas control group comprised of 120 males and 86 females.
In this study it has been observed that the mean post-meal blood sugar has significantly decreased in group, which was administered with Vitamin-C compared to control group. Fasting blood sugar is observed to have a significant decrease in group B. It has been observed that there has been a significant reduction in HbA1c in group B, which was given Vitamin-C supplements compared to group A which was control group. Plasma Vitamin-C levels had a significant increase in study group.
DISCUSSION:
Normal dietary consumption of Vitamin-C has been studied in detail in some studies but observed to be of no use in managing diabetes and in lowering the risk of prospective diabetes. Many researchers used higher amounts of Vitamin-C intake than usual doses and demonstrated that glycemic management requires larger doses[i],[ii].
The inclusion of Vitamin-C supplementation to standard therapy was tested in 70 patients diagnosed with T2DM treated with metformin and were randomized to 500 mg Vitamin-C twice a day for 12 weeks or placebo. Those given Vitamin-C were reported to have lower levels of HbA1c, fasting and post-meal blood glucose compared to placebo considering all metformin treatments[iii].
Health problems like diabetic micro vascular angioplasty due to RBC vulnerability, because erythrocytes lack carriers of sodium-dependent Vitamin-C and therefore are relying on carriers of glucose that actually take up Vitamin-C. Fasting blood glucose and Vitamin-C daily consumption are significant predictive factors of Vitamin-C plasma levels[iv]. Oxidative stress, which can be caused by a deficiency of Vitamin-C, also contributes to changes in signaling pathways and possible damage to the tissue[v]. Glucose carriers have been shown to be able to prevent the absorption of dehydroascorbic acid, the oxidized form of Vitamin-C, through elevated blood glucose levels competitively[vi]. In this study, analysis showed a significant decrease in blood glucose levels in Vitamin-C group relative to the control group and a significant decrease in serum HbA1c in Vitamin-C supplemented patients over 21 days.
In their research on sppplementaion of Vitamin-C, P Sridulyakulet et al[vii]found similar findings which could reverse the deficiency of endolithelial cells caused by diabetes in mesenteric microcirculation in STZ rats. It has also been demonstrated that the increase in serum antioxidant glutathione as well as drop in glycosylated hemoglobin following long term ascorbic acid supplementation are interrelated[viii].
CONCLUSION:
Levels of Vitamin-C are lower among people with T2DM and thus the nutritional needs or need for supplementation of Vitamin-C may be higher in diabetic patients. Supplements of Vitamin-C can significantly reduce levels of blood glucose and HbA1c in type 2 diabetes patients.
Acknowledgement: Authors acknowledge the immense help received from the scholars whose articles are cited and included in references of this manuscript. The authors are also grateful to authors / editors / publishers of all those articles, journals and books from where the literature for this article has been reviewed and discussed.
Conflict of Interest: Nil
Source of Funding: Nil
Englishhttp://ijcrr.com/abstract.php?article_id=2705http://ijcrr.com/article_html.php?did=2705
International Diabetes Federation IDF diabetes atlas 2019. [(accessed on June 20 2020)]; Available online: http://www.diabetesatlas.org.
Ajonish Kamble, Ranjit S. Ambad, Mangesh Padamwar, Anupam Kakade, Meenakshi Yeola. To study the effect of oral vitamin D supplements on wound healing in patient with diabetic foot ulcer and its effect on lipid metabolism. Int. J. Res. Pharm. Sci., 2020, 11(2), 2701-2706
D. H. Alamdari, K. Paletas, T. Pegiou, M. Sarigianni, C. Befani, and G. A. Koliakos, "A novel assay for the evaluation of the prooxidant-antioxidant balance, before and after antioxidant vitamin administration in type II diabetes patients," Clinical Biochemistry, Clin Biochem. 2007 Feb;40(3-4):248-54. Epub 2006 November 21
Ranjit Sidram Ambad, Gaikwad S B, Anshula G, Nandkishor Bankar. Polyherbal antidiabetic drug: An approach to cure diabetes. Int. J. Res. Pharm. Sci., 2020, 11(2), 2679-2683
Nutrient Reference Values for Australia and New Zealand Including Recommended Dietary Intakes. NHMRC Guidelines. 2005; Sept:119–125. Available from: https://www.nhmrc.gov.au/_files_nhmrc/publications/attachments/n35.pdf. Accessed December 30, 2014.
Suraj P Wagh, Shweta P Bhagat, Nandkishor Bankar, Karan Jain. Relationship between Hypothyroidism and Body Mass Index in Women: A Cross-Sectional Study International Journal of Current Research and Review. Vol 12 Issue 12, 2020 June, 48-51, doi: http://dx.doi.org/10.31782/IJCRR.2020.12129
Mann GV. Hypothesis: the role of Vitamin-C in diabetic angiopathy. Perspect Biol Med. 1974;17(2):210–217.
Opara EC. Role of oxidative stress in the etiology of type 2 diabetes and the effect of antioxidant supplementation on glycemic control. J Investig Med. 2004;52(1):19–23.
Carr A, Frei B. Does Vitamin-C act as a pro-oxidant under physiological conditions? FASEB J. 1999 Jun; 13(9):1007-24.
Will JC, Byers T. Does diabetes mellitus increase the requirement for Vitamin-C? Nutr Rev. 1996 Jul; 54(7):193-202
Montonen J, Knekt P, Järvinen R, Reunanen A. Dietary antioxidant intake and risk of type 2 diabetes. Diabetes Care. 2004 Feb; 27(2):362-6.
Czernichow S, Couthouis A, Bertrais S, Vergnaud AC, Dauchet L, Galan P, Hercberg S. Antioxidant supplementation does not affect fasting plasma glucose in the Supplementation with Antioxidant Vitamins and Minerals (SU.VI.MAX) study in France: association with dietary intake and plasma concentrations. Am J Clin Nutr. 2006 Aug; 84(2):395-9.
Dakhale GN, Chaudhari HV, Shrivastava M. Supplementation of Vitamin-C reduces blood glucose and improves glycosylated hemoglobin in type 2 diabetes mellitus: a randomized, double-blind study. Adv Pharmacol Sci. 2011;2011:195271.
Tu H, Li H, Wang Y, Niyyati M, Wang Y, Leshin J, Levine M. Low Red Blood Cell Vitamin-C Concentrations Induce Red Blood Cell Fragility: A Link to Diabetes Via Glucose, Glucose Transporters, and Dehydroascorbic Acid. E Bio Medicine. 2015 Nov; 2(11):1735-50.
Lamb RE, Goldstein BJ. Modulating an oxidative-inflammatory cascade: potential new treatment strategy for improving glucose metabolism, insulin resistance, and vascular function. Int J Clin Pract. 2008 Jul; 62(7):1087-95.
Girgis C., Christie-David D., Gunton J. Effects of vitamins C and D in type 2 diabetes mellitus. Nutr Diet Suppl. 2015;7:21–28.
P. Sridulyakul, D. Chakraphan, and S. Patumraj, “Vitamin-C supplementation could reverse diabetes-induced endothelial cell dysfunction in mesenteric microcirculation in STZ-rats,” Clinical Hemorheology and Microcirculation, vol. 34, no. 1-2, pp. 315–321, 2006.
E. Szaleczky, J. Prechl, E. Ruzicska et al., “Reduction of glycated hemoglobin levels by long term, high dose ascorbic acid supplementation in healthy and diabetic patients,” Medical Science Monitor, vol. 4, no. 2, pp. 241–244, 1998.
Radiance Research AcademyInternational Journal of Current Research and Review2231-21960975-52411213EnglishN2020July6HealthcareDermatological Manifestations of COVID-19: A Review Based on Existing Reports
English6568Tarun KumarEnglish Siddhartha DuttaEnglish Rajit SahaiEnglish Sameer KhasbageEnglish Rajesh KumarEnglish Sudeshna BanerjeeEnglishThe pandemic of severe acute respiratory syndrome Coronavirus 2(SARS-CoV-2) infections started with few unknown cases of pneumonia associated with the Wuhan district of China. This has led to a huge load of cases and deaths due globally these days. As of now, most infections are self-limiting, and approximately 15% of infected adults can turn up critical to developing severe pneumonia and requires supplemental oxygen therapy. The causative virus was isolated from lower respiratory tract samples of infected patients, found to be a novel Coronavirus (nCoV). The clinical signs and symptoms of COVID-19 are highly variable and include the most common symptoms as fever, dry cough, and fatigue. This highly infectious virus usually affects the respiratory tract; hence the cutaneous manifestations are often ignored and not reported. Cutaneous manifestations are quite common in various viral infections, and the scenario can be similar in COVID-19. The asymptomatic period of about 14 days, even after infection leads to a delay in the diagnosis of this condition. In view of such conditions, cutaneous manifestations if present can serve as a signal for the incubating infection. High levels of clinical suspicion and judgment can diagnose the condition early hence help in early intervention. This article reviews all the possible dermatological manifestations reported in the patients of COVID-19 in the online scientific platforms.
EnglishCOVID-19, Coronavirus, Dermatological manifestation, Skin, SARS-CoV-2Introduction
Presently, the whole world is in distress due to the novel Coronavirus, which has put it on a standstill. It started with few unknown cases of pneumonia associated with unusual etiology were initially reported in Wuhan district of China in December 2019.1 Later, the pathogen was isolated from lower respiratory tract samples of infected patients, found to be a novel Coronavirus (nCoV), and was named severe acute respiratory syndrome Coronavirus 2 (SARS-CoV-2).2 Earlier, the nCoVwas found to be quickly spreading inside Hubei Province, and later it got spread to other countries of the world.3 It was declared as an emergency by the World Health Organization(WHO), and later by the midst of February 2020, the SARS-CoV-2 had already spread across the world.2,3 WHO named it Coronavirus Disease 2019 (COVID-19), and further, on March 11, 2020, it was declared as a pandemic.2,3,4 As of May 10, 2020, a total of 3,862,676 cases and 265,961 deaths have been confirmed by the WHO.5 Europe, USA, Eastern Mediterranean are worst hit apart from the reach in Western Pacific, South-East Asia, and the African region.5 The clinical signs and symptoms of COVID-19 are highly variable and include common symptoms like fever, dry cough, and fatigue.6 The less common symptoms are myalgia, rhinorrhea, headache, conjunctivitis, sore throat, diarrhea, anosmia or ageusia, skin rash or discoloration of fingers or toes.6 There is also instability in the vital parameters like temperature, pulse oximetry saturation, and changes in chest radiological findings in X-ray and Chest CT scan.7 In COVID-19, the patients most report with respiratory symptoms, which can range from mild flu to severe respiratory distress.7 The SARS-CoV-2 virus enters the cells through the angiotensin-converting enzyme 2 (ACE2) receptor, found on the surface of cells, and lungs are the primary site of infection.8, 9 Of the above varied symptoms mentioned, all symptoms are not essentially present in every successive patient, and besides, as this infective disease is primarily respiratory in nature, for this reason, the cutaneous manifestations have not been widely reported.7 This article is a review of all the possible dermatological manifestations reported by various researchers as reported by them in the online scientific platforms and indexed journals.
Dermatological manifestation of COVID-19
An early report by Recalcati S et al.. stated that dermatologists working with COVID-19 patients in Italy analyzed a group of 88 confirmed positive patients, among which 18 developed skin symptoms.10 Eight patients got the skin symptoms at the onset, and 10 of them developed it after hospitalization. Amongst the COVID-19 patients, the most familiar expression of all was the presence of an erythematous rash or a patchy red rash. A few developed widespread urticaria or hives, and one developed chickenpox-like blisters.10 The trunk was the most familiar site to be affected, and the pruritis was associated with the lesions being low or even absent. The lesions were seen to heal within a few days, and they could not find any correlation with the severity of the disease.10
A report from Thailand, Joob B et al. 2020, described a COVID-19 patient who was initially misdiagnosed with dengue fever. He presented with petechiae and rash common as seen in dengue. Later on, the patient developed respiratory distress and was found to be 2019-CoV positive.11 Y. Zhang et al. from Wuhan(China), reported cases of Acro-ischemia with finger/toe cyanosis, skin bulla and dry gangrene in 7 patients.12 J. Jimenez-Cauhe et al. reported a case from Spain stating Erythemato-purpuric, coalescing macules in Flexural and peri-axillary regions within 3 days of hospitalization.13 Henry et al. from France reported a case with disseminated erythematous plaques eruption on face, hand and feet within 48 hours before the onset of respiratory symptoms and associated with pruritis.14 Estébanez et al. from Spain reported a case with pruritic lesions/ confluent, erythematous-yellowish papules on the heel, 13 days after being positive of SARS-CoV-2. The lesions persisted and got hardened and pruritic.15 Similar reports from Tehran, Iran by Kamali Aghdam stated Cutaneous mottling in a 15-day-old neonate who was admitted with fever, lethargy and respiratory distress without cough.16 Mazzotta et al. reported a case from Italy stating a 13-year-old male with erythematous-violet, rounded lesions with blurred limits on the plantar surface of 1st right toe and dorsal surface of the 2nd toe on both feet associated with intense itching andburning on the foot lesions.17Alramthan et al. from Qatar reported acral ischemic lesions presenting as red-purple papules on the dorsal aspect of fingers.18 Athanassios Kolivras et al. from Brussels, Belgium stated a case report with acute-onset, violaceous, infiltrated, and painful plaques on the toes and lateral aspect of the feet which began 3 days after onset of respiratory symptoms and a dry cough.19 Sachdeva et al. from Milan, Italy reported 3 cases of dermatological manifestation associated with COVID-19. The dermatological manifestation varied presentation like a maculopapular itchy rash resembling Grover disease, diffuse maculopapular exanthema(morbilliform), macular hemorrhagic rash, Papular-vesicular, and pruritic eruption.20 In their review of 1099 cases of COVID-19 infection from mainland China, Guan et al. reported 2 patients (0.2%) had a rash.21
C. Galván Casas et al. did a nationwide survey of 375 cases in Spain and classified the dermatological manifestation into five types of clinical patterns. The authors stated that the vesicular eruptions were seen to appear early in the course of the disease whereas, the pseudo?chilblain pattern seems to have a delayed appearance in the course of the COVID?19 disease.22
The skin lesions of COVID-19 patients were classified as given in table I.
COVID toes
Sarah Young, in an article, mentions “COVID toes is a nonspecific term that describes a purple or pink discoloration often with papules involving the tips of the toes. There can be varied causes, among which impaired blood flow to the toes or chilblain-like toes can be one of them.”23 In view of the fact that COVID-19 is creating a pro-inflammatory state, therefore the patients have a higher risk of developing clots. Though, they could not conclude because of the lack of robust evidence and early findings but stated that systemic inflammation and clotting can be an apparent cause of COVID toes.23,24
Conclusion
The presentation of rash or cutaneous manifestation associated with has been found to have a varied or diverse manifestation. It can confuse the medical practitioner between rashes like hives, a drug reaction, or chilblains. The preexisting rash in cases of COVID-19 before showing the respiratory symptoms makes it hard to pick up and easy to miss the cases from early diagnosis of COVID-19. Due to the lack of enough data and evidence, the typical or diagnostic presentation of the rash in COVID-19 has been a grey area till now. Until more is known, clinicians must have a high intent of suspicion regarding any cases of rash that comes to them. The rash should drive the physician to enquire regarding other symptoms of COVID-19 with a proper history, and other clinical clues, to decide whether the patient should be tested for the disease. This will ascertain an early diagnosis and treatment of the patient suffering from COVID-19.
Acknowledgment: Authors acknowledge the immense help received from the scholars whose articles are cited and included in references of this manuscript. The authors are also grateful to authors / editors / publishers of all those articles, journals and books from where the literature for this article has been reviewed and discussed.
Conflict of Interest: None declared
Source of funding: No source of funding
Englishhttp://ijcrr.com/abstract.php?article_id=2706http://ijcrr.com/article_html.php?did=2706
Jin YH, Cai L, Cheng ZS, Cheng H, Deng T, Fan YP et al., for the Zhongnan Hospital of Wuhan University Novel Coronavirus Management and Research Team, Evidence-Based Medicine Chapter of China International Exchange and Promotive Association for Medical and Health Care (CPAM). A rapid advice guideline for the diagnosis and treatment of 2019 novel Coronavirus (2019-nCoV) infected pneumonia (standard version). Mil Med Res. 2020 February 6;7(1):4. doi: 10.1186/s40779-020-0233-6.
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Ng OT, Marimuthu K, Chia PY, et al.. SARS-CoV-2 infection among travelers returning from Wuhan, China. N Engl J Med. 2020 March 12. doi: 10.1056/NEJMc2003100. [Epub ahead of print].
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Wang D, Hu B, Hu C et al. Clinical Characteristics of 138 Hospitalized Patients With 2019 Novel Coronavirus-Infected Pneumonia in Wuhan, China. JAMA. 2020 Feb 7. doi: 10.1001/jama.2020.1585. [Epub ahead of print].
Guo YR, Cao QD, Hong ZS, Tan YY, Chen SD, Jin HJ, et al.. The origin, transmission and clinical therapies on Coronavirus disease 2019(COVID-19) outbreak - an update on the status. Mil Med Res. 2020 March 13;7(1):11. doi: 10.1186/s40779-020-00240-0
Zhai P, Ding Y, Wu X, Long J, Zhong Y, Li Y. The epidemiology, diagnosis and treatment of COVID-19. Int J Antimicrob Agents. 2020 Mar 28:105955. doi: 10.1016/j.ijantimicag.2020.105955. [Epub ahead of print]
Recalcati S. Cutaneous manifestations in COVID?19: a first perspective. J Eur Acad Dermatol Venereol. 2020 March 26. doi: 10.1111/jdv.16387. [Epub ahead of print] PubMed PMID: 32215952.
Joob B, Wiwanitkitet V. COVID-19, can present with a rash and be mistaken for dengue. J Am. Acad. Dermatol. 82 May (2020) e177.DOI: https://doi.org/10.1016/j.jaad.2020.03.036
Zhang Y, Cao W, Xiao M, Li YJ, Yang Y, Zhao J, Zhou X, Jiang W, Zhao YQ, Zhang SY, Li TS. [Clinical and coagulation characteristics of 7 patients with critical COVID-2019 pneumonia and acro-ischemia]. Zhonghua Xue Ye Xue Za Zhi. 2020 Mar 28;41(0):E006. Chinese. doi: 10.3760/cma.j.issn.0253-2727.2020.0006. Epub ahead of print. PMID: 32220276.
J. Jimenez-Cauhe, D. Ortega-Quijano, M. Prieto-Barrios, Om Moreno-Arrones, D. Fernandez-Nieto, Reply to “COVID-19 can present with a rash and bemistaken for Dengue”: petechial rash in a patient with COVID-19 infection. J. Am. Acad. Dermatol. April 10, 2020; pii: S0190-9622(20)30556-9.doi:http://dx.doi.org/10.1016/j.jaad.2020.04.016 [Epub ahead of print].
D. Fernandez-Nieto, D. Ortega-Quijano, G. Segurado-Miravalles, C. Pindado Ortega, M. Prieto-Barrios, J. Jimenez-Cauhe, Comment on: cutaneous manifestations in COVID-19: a first perspective. Safety concerns of clinical images and skin biopsies, J. Eur. Acad. Dermatol. Venereol. (April 15) (2020), doi: http://dx.doi.org/10.1111/jdv.16470 [Epub ahead of print]
A. Estébanez, L. Pérez-Santiago, E. Silva, S. Guillen-Climent, A. García-Vázquez,M. Ramón. Cutaneous manifestations in COVID-19: a new contribution, J. Eur. Acad. Dermatol. Venereol. (April 15) (2020), doi:http://dx.doi.org/10.1111/jdv.16474 [Epub ahead of print].
M. KamaliAghdam, N. Jafari, K. Eftekhari. Novel Coronavirus in a 15-day-old neonate with clinical signs of sepsis, a case report, Infect. Dis. (Lond). 52 (June6) (2020) 427–429, doi:http://dx.doi.org/10.1080/23744235.2020.1747634Epub 2020 Apr 1
F. Mazzotta, T. Troccoli, Acute Acro-Ischemia in the Child at the time of COVID-19. DermatologiaPediatrica, Bari, (2020) In press. Cited from URL:https://www.fip-ifp.org/wp-content/uploads/2020/04/acroischemia-ENG.pdf [Accessed on May 10, 2020]
A. Alramthan, W. Aldaraji, A case of COVID-19 presenting in clinical picture resembling chilblains disease. First report from the Middle East. Clin Exp Dermatol. (2020) April 17. doi: https://doi.org/10.1111/ced.14243. [Epubahead of print]
Kolivras A, Dehavay F, Delplace D, Feoli F, Meiers I, Milone L. Coronavirus (COVID-19) infection-induced chilblains: A case report with histopathologic findings. JAAD Case Rep. 2020 Apr 18. doi: 10.1016/j.jdcr.2020.04.011. [Epub ahead of print]
Sachdeva M, Gianotti R, Shah M, Lucia B, Tosi D, Veraldi S et al. Cutaneous manifestations of COVID-19: Report of three cases and a review of literature. J Dermatol Sci. 2020 Apr 29:S0923-1811(20)30149-3. doi: 10.1016/j.jdermsci.2020.04.011. Epub ahead of print. PMID: 32381430; PMCID: PMC7189855.
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C. GalvánCasas A.Català G. Carretero Hernández P. Rodríguez?Jiménez D. Fernández Nieto A. Rodríguez?Villa Lario et al. Classification of the cutaneous manifestations of COVID?19: a rapid prospective nationwide consensus study in Spain with 375 cases. Br. J. Dermatol 2020 April 29. doi: https://doi.org/10.1111/bjd.19163 [Epub ahead of print]
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Radiance Research AcademyInternational Journal of Current Research and Review2231-21960975-52411213EnglishN2020July6HealthcareImpact of Basic Training Programme On Medical Teachers - A Useful Pathway To Success
English6974Aruna KharkarEnglish Suvarna GulanikarEnglish Anirudha GulanikarEnglish G.A. ShroffEnglishObjectives: Change in concept of medical education from the traditional to the new learning styles needs more Workshops on Medical education for refreshing the knowledge of medical teachers. Main objective of our research was to assess medical teachers before and after Medical Education training. Research is based on a retrospective questionnaire-based study.
Method: Basic medical education workshops were conducted on 16 to 18 April 2013, 7 to 9 January 2014, 29 September to 1 October 2014, 17 to 19 March 2015 and 11 to 12 February 2020 at MEU, MGM Medical College, Aurangabad, Maharashtra. Total of 140 faculties from various departments participated in workshops. Each participant filled a pre-test questionnaire before the beginning of workshop and a post-test questionnaire after the completion of workshop. Scores obtained in the pre and post-test were compared. Each workshop conducted for eight hours per day for three days and participants gave effective feedback at the end of workshop.
Result: Statistical analysis suggests the significant improvement in the knowledge of participants [P=90% replied that it was well planned, interactive and time-bound, had responsive, expert faculties and wants frequent organisation of such workshops in future.
Conclusion: Organisation of medical education workshop at regular interval for the medical teachers is required to keep them updated with the new advances in Medical Education.
EnglishFeedback, Medical Education, Pre-test, Post-test, WorkshopINTRODUCTION-
Medical education is a demanding task. In the recent years there has been a change in the concept of medical education from the traditional to the new learning styles; therefore, high quality medical education programmes for faculty members have become essential to all medical institutions.1
With the increasing number of medical colleges, there is a shortage of train medical teachers. In India Medical Education was started in the late seventies. In 1999 Medical council of India has made it mandatory to establish medical education technology unit [MET] in every medical college. MCI made every Medical Professional mandatory, to undergo at least the basic level of training from2010.2
In recent years, with the use of new teaching and learning methods, the focus of assessment has been shifted to the use of higher cognitive abilities, communication skills, and professionalism. Focus is also shifting from competency-based education to outcome-based education and workplace performance assessment.3Here comes the role of Basic Medical Education workshops.
Recent advances in medical field have been understood and adapted in most of the medical colleges, but in practice, the methods and strategies are not systematically planned as per need of society. Medical education unit will help guide the medical teachers in experimenting, modulating, and implementing innovative technologies. This will prepare the present and future generation of medical teachers to be more effective in providing information, assessing students, curriculum planning and its implementation to produce the physician of first contact in society.
In current scenario of exploding knowledge, certain revisions are required in the format from time to time to make it more useful and acceptable both to the teachers and learners. These revisions are based on the experience gained at previous workshops as well as from feedback given by the participants and faculty members.4,5 These workshops help to implement new teaching and learning methods and more focus to be given in the innovative teaching-learning methods as suggested by MCI.
The key to successful initiation and implementation to meet the needs of medical education is to develop the train faculties. So the training programmes for MGM medical college faculties, Aurangabad were organised, and the effect of training was evaluated. Main objective of this project was to observe the improvement in teaching-learning methodology of medical faculty before and after the workshop.
MATERIAL AND METHODS
Five consecutive workshops on basic medical education were conducted on 16 to 18 April 2013, 7 to 9 January 2014, 29 September to 1 October 2014, 17 to 19 March 2015 and 11 to 12 February 2020 at MEU, MGM Medical College, Aurangabad, Maharashtra. These workshops were guided and observed by faculty from nodal centre of medical education unit, KEM, Mumbai and faculty from Maharashtra medical council.
Total 140 faculties participated in five training programme. Participants were Professor, AssociateProfessor and Assistant Professor from preclinical, Para clinical and clinical department. Random selection of participants was done for each session. Training sessions were interactive and conducted by facilitators from various departments and MCI observer.
Englishhttp://ijcrr.com/abstract.php?article_id=2707http://ijcrr.com/article_html.php?did=2707Radiance Research AcademyInternational Journal of Current Research and Review2231-21960975-52411213EnglishN2020July6HealthcareStudy of Cardiovascular Dysfunctions in Interstitial Lung Disease patients by Correlating the Levels of Serum NT PRO BNP and Microalbuminuria (Biomarkers of Cardiovascular Dysfunction) with Echocardiographic, Bronchoscopic and High-Resolution Computed Tomography Findings of these ILD Patients
English7581Dr. Raunak DasEnglishAim: More than 150 known factors associated with ILD and prevalence are uncommon with usual clinical presentation of exertional dyspnea and cough, with finding on examination often limited to fine inspiratory crackles on auscultation.Diagnosis can be made by combination of clinical, radiological and pathological features.
Methods: This is a prospective study constituting 60 cases of ILD conducted to study the cardiovascular dysfunctions associated with interstitial lung diseases with special reference to serum NT PRO BNP and microalbuminuria as bio-markers of cardiovascular dysfunction and co-relating the level of serum NT PRO BNP and microacclbuminuria with echocardiographic, bronchoscopic and HRCT findings in ILD patients.
Results: When the correlation between major 2D Echo findings, raised serum NT PRO BNP and microalbuminuria was made it was found that out of total 24 cases of PAH all 24 cases(100%) had raised serum NT PRO BNP and 23 cases(95.83%) had microalbuminuria, out of total 8 cases of diastolic dysfunction all these 8 cases(100%) had raised serum NT PRO BNP and 4 cases(50%) had microalbuminuria, out of 26 cases of normal 2D Echo 4 cases(15.38%) had raised serum NT PRO BNP and 2 cases(7.69%) had microalbuminuria.
Result: Pulmonary hypertension is a very important predictor of mortality; early detection can help in inducting early intervention and can delay mortality. Hence 2D Echo, serum NT Pro BNP and microalbuminuria evaluation should be included in the evaluation of all ILD cases.
EnglishILD, Serum NT PRO BNP and microalbuminuria, Cardiovascular dysfunction, Clinicoradiological profile of patientshttp://ijcrr.com/abstract.php?article_id=2708http://ijcrr.com/article_html.php?did=2708