Longitudinally extensive transverse myelitis following ChAdOx1 nCoV-19 vaccine.

Transverse myelitis (TM) has been reported in association with various vaccinations. Herein we describe a case of longitudinally extensive transverse myelitis (LETM) associated with vaccination with ChAdOx1 nCoV-19 (COVISHIELD) vaccine. A 59-year-old woman with no prior co-morbidities presented with lower extremity numbness, weakness, acute urinary retention, and constipation. Numbness gradually extended up to the lower costal margin with band like sensation. She had received the vaccine 5 days prior to the onset of the symptoms. Extensive diagnostic evaluation effectively ruled out causes other than vaccination-associated transverse myelitis. Following treatment with intravenous methylprednisolone, the patient made a significant recovery. TM may be associated with vaccination against the novel ChAdOx1 nCoV-19 vaccine and we believe this to be the first report from India of LETM associated with this vaccine.

Rescue therapy with intravenous immunoglobulin in severe refractory dengue: A pilot study.

Background: Severe dengue causes more than 22,000 deaths annually worldwide. Complicated dengue has high mortality of 44-72%. Disordered immune system with capillary leak and thrombocytopenia are hallmark of complicated dengue. Intravenous immunoglobulin (IV Ig) therapy has shown to be effective in complicated dengue in pediatric age group with refractory shock, but studies in adults are lacking. Its immunoresuscitative role is not yet fully explored in critically ill patients with severe dengue. Methods: This is retrospective observational study of patients with complicated dengue fever who were administered IV Ig therapy in a tertiary care hospital of southern India from 01 Jan 2018 to 31 Dec 2019. Results: A total of 999 patients with dengue were admitted; 754 (75.47%) were males, and 245 (24.53%) were females. A total of 402 (40.24%) patients presented with warning signs. Bleeding was seen in 121 patients (12.11%); 102 (10.21%) had shock; 29 (2.90%) had acute kidney injury and 24 (2.40%) had adult respiratory distress syndrome. Overall, four people died (mortality rate: 0.40%). IV Ig in the dose of 0.4 g/kg for 5 days was used in 13 critically ill patients where standard therapy failed, 9 patients with refractory shock (which included three with myocarditis with refractory shock), 2 with encephalitis, 2 in hemophagocytic lymphohistiocytosis. Two patients died, one with myocarditis with refractory shock and another with refractory shock. Conclusion: IV Ig therapy in critically ill patients with complicated dengue can be used as a rescue therapy.

Controlled evaLuation of Angiotensin Receptor Blockers for COVID-19 respIraTorY disease (CLARITY): statistical analysis plan for a randomised controlled Bayesian adaptive sample size trial.

The CLARITY trial (Controlled evaLuation of Angiotensin Receptor Blockers for COVID-19 respIraTorY disease) is a two-arm, multi-centre, randomised controlled trial being run in India and Australia that investigates the effectiveness of angiotensin receptor blockers in addition to standard care compared to placebo (in Indian sites) with standard care in reducing the duration and severity of lung failure in patients with COVID-19. The trial was designed as a Bayesian adaptive sample size trial with regular planned analyses where pre-specified decision rules will be assessed to determine whether the trial should be stopped due to sufficient evidence of treatment effectiveness or futility. Here, we describe the statistical analysis plan for the trial and define the pre-specified decision rules, including those that could lead to the trial being halted. The primary outcome is clinical status on a 7-point ordinal scale adapted from the WHO Clinical Progression scale assessed at day 14. The primary analysis will follow the intention-to-treat principle. A Bayesian adaptive trial design was selected because there is considerable uncertainty about the extent of potential benefit of this treatment.Trial registrationClinicalTrials.gov NCT04394117 . Registered on 19 May 2020Clinical Trial Registry of India CTRI/2020/07/026831Version and revisionsVersion 1.0. No revisions.

Continuous Ambulatory Peritoneal Dialysis Peritonitis Guidelines - Consensus Statement of Peritoneal Dialysis Society of India - 2020.

Continuous ambulatory peritoneal dialysis (CAPD) related peritonitis is a major cause of technique failure, morbidity, and mortality in patients on CAPD. Its prevention and management is key to success of CAPD program. Due to variability in practice, microbiological trends and sensitivity towards antibiotics, there is a need for customized guidelines for management of CAPD related peritonitis (CAPDRP) in India. With this need, Peritoneal Dialysis Society of India (PDSI) organized a structured meeting to discuss various aspects of management of CAPDRP and formulated a consensus agreement which will help in management of patients with CAPDRP.

Modified Short Proximal Femoral Nail for Intertrochanteric Fractures of Femur in Indian Patients - our Experience.

INTRODUCTION: Proximal femoral nail (PFN) is a commonly used implant for intertrochanteric fractures which is designed according to western femoral measurements. However, anthropometry of proximal femur in Indian and in general, Asian, are smaller. So a modified short PFN with smaller dimensions was developed. This study analyses the radiological and functional outcome of treatment of intertrochanteric fractures with modified short PFN. MATERIALS AND METHODS: A retrospective study analysed 120 adult patients operated between 2014-2017 using modified short PFN for intertrochanteric fractures, having a minimum follow-up of 12 months. Clinical and radiological parameters including tip-apex distance (TAD), position of tip of lag screw in femoral head, lateral slide of lag screw as well as length of anti-rotation screw were measured. Final functional outcome was assessed using Barthel's index and Kyle's criteria. RESULTS: Good reduction was achieved in 90.83% cases and 79.16% had ideal placement of lag screw in femoral head. Intra-operative difficulties were encountered in 13.33% (n=16). Mean TAD AP (anteroposterior) was 11.8mm, TAD LAT (lateral) was 11.0mm and mean TAD TOT was 22.8mm. Overall mean lateral slide was 3.20mm and it was more in unstable fracture. We had five mechanical failures, one patient with screw breakage without loss of reduction and two peri-implant fractures after union. 81.66% returned to pre-injury levels of activity with 88.33% good to excellent outcome as per Kyle's criteria. CONCLUSION: Although, not devoid of complications, modified short PFN results in good functional recovery of patients with intertrochanteric fractures of femur.

Clinicopathological Spectrum of Glomerular Diseases in Adolescents: A Single-center Experience over 4 Years.

The spectrum of biopsy-proven glomerular disease was studied from a single center in Northwestern India, among adolescents aged 13-19 years. From January 2009 to December 2012, a total of 177 patients with biopsy-proven glomerular disease were studied. The same pathologist reported all the biopsy specimens after subjecting to light, immunofluorescence, and electron microscopy. The clinical profile and laboratory findings of the patients were correlated with the histopathological spectrum of glomerular diseases. Males formed 71.19% (n = 126) and the remaining 28.81% (n = 51) were females. Lupus nephritis had a strong female predominance, whereas minimal change disease (MCD) and focal segmental glomerulosclerosis (FSGS) had a male predominance. Nephrotic syndrome was the indication for biopsy in 65% of the cases. Rapidly progressive renal failure and acute nephritis were the next common indications accounting for 14% and 7%, respectively. FSGS was the most common glomerular disease in adolescents (n = 45, 25.4%). The next common were MCD and lupus nephritis each contributing 21.6% and 10.7%, respectively. Primary glomerular diseases accounted for 84.75% (n = 150) of the total. The remaining 15.25% (n = 27) were attributed to secondary glomerular diseases, of which lupus nephritis was the most common, i.e., in 70.4% patients (n = 19). FSGS was the most common histology in adolescent nephrotic participants (37%). MCD was the next common, found in 31% of nephrotic patients. Electron microscopy changed the diagnosis made by light microscopy and immunofluorescence in 5.6% cases only, and it confirmed the diagnosis in another 21.6%. Kidney biopsy in adolescents is a safe procedure. The spectrum of glomerular diseases in adolescents is different from that seen in adults and smaller children.

Temporal Association Between PLA2R Antibodies and Clinical Outcomes in Primary Membranous Nephropathy.

INTRODUCTION: Autoantibodies to M-type phospholipase A2 receptor (aPLA2R) are seen in two-thirds of patients with primary membranous nephropathy (PMN) and are associated with disease activity. However, the precise temporal dynamics between the presence and amount of aPLA2R in circulation, as well as the clinical activity, are not known. We evaluated the temporal association between disease activity and serum aPLA2R during and after treatment in PMN. METHODS: The study included all patients with PMN and elevated aPLA2R who were started on immunosuppressive therapy for persistent nephrotic syndrome at a single center between December 2014 and December 2015. Serum samples were tested for aPLA2R at baseline and at monthly intervals for 6 months. Clinical details were collected monthly for 9 months. Serological remission was defined as negative aPLA2R in 2 consecutive samples. Clinical remission was defined by standard criteria. RESULTS: A total of 30 patients with PMN were studied. Of these, 28 (93%) had elevated levels at baseline, whereas 2 (7%) became positive after 1 month. The mean age was 33.2 ± 1 (range, 13-52) years. Median baseline aPLA2R titer was 163.41 (range, 70-291.01) RU/ml. A total of 24 patients (80%) achieved serological remission by 6 months. Among all the serological responders, 54% had achieved negative aPLA2R by the end of the first month. Clinical remission was observed in 20 patients (67%). Serological and clinical remission were noted at 2.7 ± 1.71 and 5.05 ± 2.64 months, respectively. CONCLUSION: In patients with aPLA2R-associated PMN, reduction in circulating aPLA2R precedes clinical remission. Persistence of aPLA2R at the end of therapy is associated with clinical resistance.

A Single-center Experience of Kidney Transplantation from Donation after Circulatory Death: Challenges and Scope in India.

Donation after circulatory death (DCD) has never been attempted in India because of legal constraints and lack of guidelines for the withdrawal of life support in end-of-life situations. The present report describes the initial experience of transplantation of organs from DCD donors in a tertiary care center in India. Between 2011 and 2015, five donors had kidneys retrieved after cardiac arrest. These patients were declared dead after waiting for 5 min with no electrocardiographic signal on monitor following cardiopulmonary resuscitation (CPR), which was restarted in three patients till organ retrieval. All donors received heparin and underwent rapid cannulation of aorta, infusion of preservative cold solution, and immediate surface cooling of organs during retrieval surgery. 9/10 kidneys were utilized. Mean donor age was 29.6 ± 16.3 years, M:F 4:1 and mean age of recipients was 38.7 ± 10.8 years, M:F 7:2. Seven patients required dialysis in postoperative period. Mean postoperative day 0 urine output was 1.9 ± 2.6 L. Baseline creatinine achieved was 1.38 ± 0.35 mg/dl after a mean duration of 26.12 ± 15.4 days. Kidneys from donors where CPR was continued after the declaration of death (n = 3) had better recovery of renal function (time to reach baseline creatinine 21.2 ± 7.2 vs. 34.3 ± 23.7 days, baseline creatinine 1.36 ± 0.25 vs. 1.52 ± 0.45 mg%). In donors without CPR, one kidney never functioned and others had patchy cortical necrosis on protocol biopsy, which was not seen in the kidneys from donors with CPR. Kidneys from DCD donors can serve as a useful adjunct in deceased donor program. Continuing CPR after the declaration of death seems to help in improving outcomes.

Anti-glomerular basement membrane disease: Case series from a tertiary center in North India.

Anti-glomerular basement (anti-GBM) disease is an uncommon disorder with a bimodal age of presentation. Patients presenting with dialysis-dependent renal failure have poor renal outcomes. There is limited data regarding the clinical presentation and outcomes of anti-GBM disease from India. We conducted this prospective study to analyze the clinical presentation and outcomes of anti-GBM disease at a large tertiary care hospital in North India over 1½ years. Subjects with a biopsy proven anti-GBM disease (light microscopic examination showing crescents and immunofluorescence examination showing linear deposition of IgG) with or without positive anti-GBM antibodies in serum were included in the study and followed-up for at least 12 months. All the patients were treated with steroids, cyclophosphamide, and plasma exchange. A total of 17 patients (nine males) were included. The mean age at presentation was 39.11 ± 16.58 (range 11-72) years. Twelve patients (70%) presented with rapidly progressive glomerulonephritis (RPGN), 4 (23.5%) presented with Goodpasture syndrome, while 1 (5.8%) had nephritic syndrome, 7 (41%) were hypertensive, and 14 (82.3%) required dialysis at the time of presentation. Four patients (23.5%) had associated anti-neutrophil cytoplasmic antibody positivity (anti-myeloperoxidase antibodies in all). Fourteen (87.5%) patients had crescentic glomerulonephritis, while 5 (31.25%) showed necrotizing (n = 4) or granulomatous (n = 1) in the vasculitis. Of 16 patients who received treatment, four (23.25%) achieved complete remission. In this single-center study, the majority of anti-GBM disease patients presented with RPGN and had crescentic glomerulonephritis on biopsy with poor treatment outcome.

Medical students' unique experience of army leadership training: a qualitative study.

OBJECTIVES: To assess the interactive experience of first year medical students attending the leadership and management course hosted by a British Army Reserve Field Hospital developed in partnership with Liverpool University. METHODS: 244 students submitted a 1000-word structured reflective learning assignment about their reaction to, learning from and any behaviour and attitude changes as a result of, the training. The assignments were thematically analysed to identify how aspects of the training had impacted upon the students' understanding of leadership and teamwork. Their comments relating to the army were analysed to gain insight into their views and experience of the training. RESULTS: Students were surprised at how enjoyable and useful they found the course. Initially they expressed scepticism about what they could learn in an army-based environment. However, the training, particularly command and planning tasks, helped them appreciate and understand the different skills individuals can bring to a team environment, and the importance of everyone contributing. While some students were challenged by aspects of the course, with support and encouragement from team-mates and the army personnel, they learned they could achieve more together. CONCLUSIONS: Teaching leadership and management skills to medical students is a challenge which can be effectively addressed by adapting and developing army training resources. Students overcame initial scepticism about participating, and learned a lot about themselves and each other. In addition, the army developed a better understanding of the doctors of the future. The expertise of the army in delivering this training was crucial to its success as the medical school could not have provided this experience unsupported.

Postradiotherapy small cell neuroendocrine carcinoma of base of tongue: An unusual clinical and site presentation.

Small cell neuroendocrine carcinoma (NEC) of the tongue is an extremely rare entity with only seven cases reported in literature till date. These are high-grade tumors with a dismal prognosis. There is much ambiguity regarding the classification, treatment protocols and prognostic factors of these tumors due to the paucity of studies. We describe an exceptionally rare and unusual case of small cell NEC of the base of tongue arising in an elderly man 6 years after receiving radiotherapy for the treatment of squamous cell carcinoma at the same site. The diagnosis was confirmed on histopathological examination and supported by immunohistochemical positivity for neuron-specific enolase, synaptophysin, chromogranin, pan-cytokeratin, and cytokeratin 7. To the best of our knowledge, this is the first case of intraoral NEC arising many years later within the irradiated field of the initial tumor.

Association of chemokine receptor CX3CR1 V249I and T280M polymorphisms with chronic kidney disease.

The chemokine fractalkine (CX3CL1) and its receptor CX3CR1 are involved in the activation of leukocytes. Two common single-nucleotide polymorphisms of the CX3CR1 gene, V249I and T280M, have been associated with reduced fractalkine signaling, leading to decreased adhesive function and leukocyte chemotaxis. We hypothesized that variation in the CX3CR1 gene could be associated with chronic kidney disease (CKD), a disease of inflammatory activation. We studied the association between CX3CR1 V249I and T280M polymorphisms, and fractalkine and highly sensitive C-reactive protein (hs-CRP) levels in 123 patients with CKD and 100 healthy controls (HCs). Genotype analysis was done by polymerase chain reaction-restriction fragment length polymorphism, and fractalkine and hs-CRP levels were analyzed by enzyme-linked immunosorbent assay. MM genotype of T280M was absent in CKD patients, while in controls it was seen in 1% of the individuals. The allele frequencies in both the groups were similar (P = 0.059). Compared to HC, M280M + T280M genotype was more frequent in CKD (P = 0.041). The frequency of II genotype of V249I was 0.8% in CKD, whereas in HC, it was 2%. I249I + V249I genotype was more frequent in CKD as compared to HC (P = 0.034). No difference in allelic frequency of V249I was noted between the two groups (P = 0.061, odds ratios = 1.74, 95% confidence intervals = 0.96-3.12). Plasma fractalkine and serum hs-CRP levels were higher in CKD subjects (P = 0.004 and P < 0.0001). No association of either genotype was found with fractalkine and hs-CRP levels. Polymorphisms at I249 and M280 genotype in CX3CR1 gene are associated with CKD; however, there was no association of fractalkine or inflammatory marker with these genotypes.

Uptake of uranium by aquatic plants growing in fresh water ecosystem around uranium mill tailings pond at Jaduguda, India.

Concentration of uranium was determined in aquatic plants and substrate (sediment or water) of fresh water ecosystem on and around uranium mill tailings pond at Jaduguda, India. Aquatic plant/substrate concentration ratios (CRs) of uranium were estimated for different sites on and around the uranium mill tailings disposal area. These sites include upstream and downstream side of surface water sources carrying the treated tailings effluent, a small pond inside tailings disposal area and residual water of this area. Three types of plant groups were investigated namely algae (filamentous and non-filamentous), other free floating & water submerged and sediment rooted plants. Wide variability in concentration ratio was observed for different groups of plants studied. The filamentous algae uranium concentration was significantly correlated with that of water (r=0.86, p<0.003). For sediment rooted plants significant correlation was found between uranium concentration in plant and the substrate (r=0.88, p<0.001). Both for other free floating species and sediment rooted plants, uranium concentration was significantly correlated with Mn, Fe, and Ni concentration of plants (p<0.01). Filamentous algae, Jussiaea and Pistia owing to their high bioproductivity, biomass, uranium accumulation and concentration ratio can be useful for prospecting phytoremediation of stream carrying treated or untreated uranium mill tailings effluent.

Gemcitabine and mitomycin induced autophagy regulates cancer stem cell pool in urothelial carcinoma cells.

Urothelial carcinoma (UC) is characterized by therapeutic resistance and frequent tumor relapse. It has been suggested that UC are driven by a rare subset of cancer stem cells (CSCs). In order to understand UC recurrence post therapy, we investigated the behavior of urothelial CSCs after exposure to commonly used chemotherapeutic agents, gemcitabine (GC) and mitomycin (MM). Although, the role of autophagy in CSC maintenance is well documented, the relationship of autophagy and CSCs with respect to drug resistance remains elusive. In the present study, we found that both GC and MM increased the percentage of CSCs in primary cultured urothelial carcinoma cells (UCC). These CSCs exhibited higher autophagy flux and higher expression of glycolytic genes. Inhibition of autophagy led to decrease in the expression of glycolysis genes. Inhibition of autophagy and glycolysis caused decrease in expression of stemness genes (Oct-4, Nanog), drug resistance genes (ABCG2, MDR1) and sensitized CSCs to GC and MM induced apoptosis. This finding suggests that autophagy and glycolysis may play a central role in drug resistance. Altogether, we conclude that autophagy may support cell survival by buffering bioenergetic demands for maintenance of high glycolytic flux in CSCs. Therefore, autophagy-based, "customized" combinatorial approaches may provide a new method to counter CSC-driven resistance and may prevent relapse in UC. The synergistic cytotoxic effect of GC/ MM with autophagy inhibitor (chloroquine) or with glycolytic inhibitor (2-deoxyglucose) may be of help in improving the outcome in patients with urothelial carcinoma of urinary bladder.

Drug-induced acute interstitial nephritis: A clinicopathological study and comparative trial of steroid regimens.

Steroids are used in the management of drug-induced acute interstitial nephritis (AIN). The present study was undertaken to compare the efficacy of pulse methyl prednisolone with oral prednisolone in the treatment of drug-induced AIN. Patients with biopsy-proven AIN with a history of drug intake were randomized to oral prednisolone (Group 1) 1 mg/kg for 3 weeks or a pulse methyl prednisolone (Group II) 30 mg/kg for 3 days followed by oral prednisolone 1 mg/kg for 2 weeks, tapered over 3 weeks. Kidney biopsy scoring was done for interstitial edema, infiltration and tubular damage. The response was reported as complete remission (CR) (improvement in estimated glomerular filtration rate [eGFR] to ≥60 ml/min/1.73 m(2)), partial remission (PR) (improvement but eGFR <60 ml/min/1.73 m(2)) or resistance (no CR/PR). A total of 29 patients, Group I: 16 and Group II: 13 were studied. Offending drugs included nonsteroidal anti-inflammatory drugs, herbal drugs, antibiotics, diuretic, rifampicin and omeprazole. There was no difference in the baseline parameters between the two groups. The biopsy score in Groups I and II was 5.9 ± 1.1 and 5.1 ± 1.2, respectively. At 3 months in Group I, eight patients each (50%) achieved CR and PR. In Group II, 8 (61%) achieved CR and 5 (39%) PR. This was not significantly different. Percentage fall in serum creatinine at 1 week (56%) was higher in CR as compared to (42%) those with PR. (P = 0.14). Patients with neutrophil infiltration had higher CR compared to patients with no neutrophil infiltration (P = 0.01). Early steroid therapy, both oral and pulse steroid, is equally effective in achieving remission in drug-induced AIN.

Proliferative glomerulonephritis with monoclonal immunoglobulin deposition disease: The utility of routine staining with immunoglobulin light chains.

Proliferative glomerulonephritis occurring as a consequence of monoclonal glomerular deposits of IgG is uncommon. It is a form of renal involvement in monoclonal gammopathy that mimics immune complex glomerulonephritis. Here, we report the first series of proliferative glomerulonephritis with monoclonal IgG deposits (PGNMID) from the Indian subcontinent highlighting use of light chain immunofluorescence (IF) in routine renal biopsy interpretation. We retrieved 6 patients diagnosed as proliferative glomerulonephritis with monoclonal IgG deposits (PGNMID) out of 160 biopsies (3.7%) with membranoproliferative patterns over 5 1/2 years (2009-2014), one of whom had recurrence 6 months post-renal transplant. Four (67%) patients presented with rapidly progressive renal failure and two (33%) with nephrotic syndrome. None of these patients had overt multiple myeloma. The predominant histologic pattern was membranoproliferative with all the biopsies showing IgG3 Kappa deposits on IF. The deposits were primarily subendothelial on electron microscopy.