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.

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.

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.

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.

Living and deceased organ donation should be financially neutral acts.

The supply of organs­particularly kidneys­donated by living and deceased donors falls short of the number of patients added annually to transplant waiting lists in the United States. To remedy this problem, a number of prominent physicians, ethicists, economists and others have mounted a campaign to suspend the prohibitions in the National Organ Transplant Act of 1984 (NOTA) on the buying and selling of organs. The argument that providing financial benefits would incentivize enough people to part with a kidney (or a portion of a liver) to clear the waiting lists is flawed. This commentary marshals arguments against the claim that the shortage of donor organs would best be overcome by providing financial incentives for donation. We can increase the number of organs available for transplantation by removing all financial disincentives that deter unpaid living or deceased kidney donation. These disincentives include a range of burdens, such as the costs of travel and lodging for medical evaluation and surgery, lost wages, and the expense of dependent care during the period of organ removal and recuperation. Organ donation should remain an act that is financially neutral for donors, neither imposing financial burdens nor enriching them monetarily.

Dental exarticulation.

Tooth exarticulation or avulsion refers to the complete displacement of the tooth out of its socket. It is a complex injury, requiring immediate intervention for optimal results. Literature indicates that prolonged dry time and improper handling may be associated with increased risk of failure. Immediate replantation of the tooth allows for immediate restoration of esthetics and phonetics. This case report presents the management of an avulsed mature tooth in a young boy, with a two-year follow-up, which had been preserved in milk after around 15-20 minutes of injury and transplanted after two hours at a dental hospital. Timely modified endodontic therapy prevented subsequent inflammatory root resorption.

Distribution of 226Ra body burden of workers in an underground uranium mine in India.

Uranium mine workers are exposed to ore dust containing uranium and its daughter products during different mining operations. These radionuclides may pose inhalation hazards to workers during the course of their occupation. The most significant among these radionuclides is (226)Ra. The measurement of radium body burden of uranium mine workers is important to assess their internal exposure. For this purpose, the radon-in-breath measurement technique has been used in the present paper. Workers at the Jaduguda mine, India, associated with different categories of mining operations were monitored between 2001 and 2007. The measurement results indicate that workers--depending on mining operation category--show (226)Ra body burdens ranging from 0.15 to 2.85 kBq. The maximum body burden was found for workers associated with timbering operations, with an average (226)Ra body burden of 0.85 ± 0.54 kBq. Overall, the average value observed for 800 workers was 0.76 ± 0.51 kBq, which gives rise to an average effective dose of 1.67 mSv per year for inhalation and 0.21 mSv per year for ingestion.

Patient-led training on patient safety: a pilot study to test the feasibility and acceptability of an educational intervention.

BACKGROUND: Training in patient safety is an important element of medical education. Most educational interventions on patient safety training adopt a 'health-professional lens' with limited consideration on the impact of safety lapses on the patient and their families and little or no involvement of patients in the design or delivery of the training. AIMS: This paper describes a pilot study to test the feasibility and acceptability of implementing a patient-led educational intervention to facilitate safety training amongst newly qualified doctors. METHOD: Patients and/or carers who had experienced harm during their care shared narratives of their stories with trainees; this was followed by a focused discussion on patient safety issues exploring the causes and consequences of safety incidents and lessons to be learned from these. RESULTS: The intervention, which will be further tested in an NIHR-funded randomised controlled trial (RCT), was successfully implemented into an existing training programme and found acceptance amongst the patients and trainees. CONCLUSION: The pilot study proved to be a useful step in refining the intervention for the RCT including identifying appropriate outcome measures and highlighting organisational issues.

Mutations in the gene encoding B1 subunit of H+-ATPase cause renal tubular acidosis with sensorineural deafness.

H+-ATPases are ubiquitous in nature; V-ATPases pump protons against an electrochemical gradient, whereas F-ATPases reverse the process, synthesizing ATP. We demonstrate here that mutations in ATP6B1, encoding the B-subunit of the apical proton pump mediating distal nephron acid secretion, cause distal renal tubular acidosis, a condition characterized by impaired renal acid secretion resulting in metabolic acidosis. Patients with ATP6B1 mutations also have sensorineural hearing loss; consistent with this finding, we demonstrate expression of ATP6B1 in cochlea and endolymphatic sac. Our data, together with the known requirement for active proton secretion to maintain proper endolymph pH, implicate ATP6B1 in endolymph pH homeostasis and in normal auditory function. ATP6B1 is the first member of the H+-ATPase gene family in which mutations are shown to cause human disease.

Empyema with pleuropulmonary mucormycosis.

Pleuropulmonary mucormycosis is relatively rare disease and that too localised disease is very rare but has got better prognosis. Maintaining a high level of suspicion is important in right clinical setting with pleuropulmonary involvement that fails to antibacterial agent either clinically or radiologically.

Review of cesarean section on maternal request in a tertiary care institute; scenario in developing country.

Mother requesting of caesarean reflects a belief among society that elective caesarean safer than vaginal delivery in term of fetus and mother. Although the study data neglecting the facts other skewed part in this issue is consideration of resources, as in developing countries, where maternal mortality is still high due to lack of adequate resources. Mother coming to obstetrician with mother's request should individualize in every case considering mother's argument, society and evidence base guideline.

Rituximab induced pulmonary fibrosis in a patient with lupus nephritis.

We describe a 26-year-old woman who was diagnosed eleven years ago with systemic lupus erythematosus and who had suffered multiple relapses. She presented with class IV lupus nephritis with thrombotic microangiopathy, for which she received three doses of rituximab along with plasmapheresis, with no response, and soon became dialysis dependent. One month after the last dose of rituximab, she presented with dyspnoea and hypoxia. A transbronchial lung biopsy revealed pulmonary fibrosis. A diagnosis of rituximab induced pulmonary fibrosis was made after excluding other causes and she was treated with intravenous methyl prednisolone with which there was marked improvement in symptoms and hypoxemia. This is the first report of rituximab induced pulmonary fibrosis in a patient with lupus nephritis.

Risk assessment due to intake of heavy metals through the ingestion of groundwater around two proposed uranium mining areas in Jharkhand, India.

Heavy metal pollution of water resources can be apprehended in East Singhbhum region which is a highly mineralised zone with extensive mining of copper, uranium and other minerals. Ten groundwater samples were collected from each site and the heavy metal analysis was done by atomic absorption spectrophotometer. Analysis of the results of the study reveals that the concentration of iron, manganese, zinc, lead, copper and nickel in groundwater of Bagjata mining area ranged 0.06-5.3 mg l(-1), 0.01-1.3 mg l(-1), 0.02-8.2 mg l(-1), 1.4-28.4 µg l(-1), 0.78-20.0 µg l(-1) and 1.05-20.1 µg l(-1), respectively. In case of Banduhurang mining area, the range was 0.04-2.93 mg l(-1), 0.02-1.1 mg l(-1), 0.01-4.68 mg l(-1), 1.04-33.21 µg l(-1), 1.24-18.7 µg l(-1) and 1.06-14.58 µg l(-1), respectively. The heavy metals were found to be below the drinking water standards (IS:10500 1993) except iron (0.3 mg l(-1)) and manganese (0.1 mg l(-1)). The hazard quotients of the heavy metals for drinking water were below 1 posing no threat due to intake of water to the people for both the areas.

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.

Risk assessment due to ingestion of natural radionuclides and heavy metals in the milk samples: a case study from a proposed uranium mining area, Jharkhand.

Ingestion of radionuclides and heavy metals through drinking water and food intake represents one of the important pathways for long-term health considerations. Milk and milk products are main constituents of the daily diet. Radionuclides and heavy metals can be apprehended in the ecosystem of the East Singhbhum region which is known for its viable grades of uranium, copper and other minerals. For the risk assessment studies, samples of milk were collected from twelve villages around Bagjata mining area and analysed for U(nat), 226Ra, 230Th, 210Po, Fe, Mn, Zn, Pb, Cu and Ni. Analysis of the results of the study reveals that the geometric mean of U(nat), 226Ra, 230Th and 210Po was 0.021, 0.24, 0.23 and 1.08 Bq l(-1), respectively. The ingestion dose was calculated to be 12.34 µSvY(-1) which is reflecting the natural background dose via the route of ingestion, and much below the 1 mSv limit set in the new ICRP recommendations. The excess lifetime cancer risk was estimated to be 1.72×10(-4) which is within the acceptable excess individual lifetime cancer risk value of 1×10(-4). The geometric mean of Fe, Mn, Zn, Cu and Ni was 4.91, 0.29, 4.77, 0.56 and 0.48 mgl(-1), respectively; whereas the daily intake was computed to be 0.44, 0.03, 0.43, 0.05 and 0.04 mg/day, respectively. Pb was not detected in any of the samples. The hazard quotient revealed that the intake of the heavy metals through the ingestion of milk does not pose any apparent threat to the local people as none of the HQ of the heavy metals exceeds the limit of 1.

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.

The utility of 1- and 3-month protocol biopsies on renal allograft function: a randomized controlled study.

Identification of pathological events in the renal allograft using protocol biopsies at predetermined time intervals may yield useful information and improve outcomes. We examined the influence of decisions taken on the basis of 1- and 3-month protocol biopsies findings on 1-year renal allograft function in a prospective randomized study. Out of 102 living-donor allograft recipients, 52 were randomized to undergo protocol biopsies and 50 controls had only indicated biopsies. All acute rejection (AR) episodes (clinical and subclinical) were treated. Calcineurin inhibitor (CNI) dose adjustments were made on clinical judgment. Baseline recipient and donor characteristics, immunosuppressive drug usage, HLA matches and 2-h cyclosporine levels were similar in both groups. At 1 and 3 months, protocol biopsies revealed borderline (BL) changes in 11.5% and 14% patients, AR in 17.3% and 12% and chronic allograft nephropathy (CAN) in 3.8% and 10%. The incidence of clinically evident AR episodes was similar in the two groups, but biopsy group had lower serum creatinine at 6 months (p = 0.0003) and 1 year (p < 0.0001). The renal functions were similar in those with normal histology and BL changes. Protocol biopsies are helpful in detecting subclinical histological changes in the graft and improving short-term renal allograft function.