LONG-TERM IMMUNOLOGICAL CONSEQUENCES OF COVID-19 ON HEALTH

SARS-Cov-2 (severe acute respiratory syndrome coronavirus) that initially came to notice in December 2019 is the agent responsible for COVID-19 is still spreading rapidly worldwide and it is presently a potent danger to the world and also to the economy. Patients with COVID-19 are still at risk of Acute Respiratory Distress Syndrome (ARDS), respiratory failure, and death. Those patients whose aged more than sixty years with comorbidities, children, and healthcare workers are highly vulnerable to this virus patient shows various symptoms most commonly cough, fever, difficulty in breathing, fatigue, sore throat. The infection could be categorized into three stages: mild infection, the pulmonary stage, and the inflammatory stage. As the COVID-19 pandemic continues, it has been clear that infection caused due to SARS-Cov-2 might be responsible for the unpredicted long-term health consequences. In addition to this, it has acute respiratory manifestations, adversely SARS-Cov-2 also affects the other organ systems. However, there is limited to the management of COVID-19 related conditions of the extrapulmonary systems. After recovery, patients remain at risk for lung disease, heart disease, and mental ailment. There may be long-term consequences of adverse effects they observed in the course of COVID-19 and during its treatment. This review provided information about the extrapulmonary manifestations of COVID-19 that may impair the urinary, cardiovascular, gastrointestinal, hematological, hematopoietic, neurological, or reproductive systems. Also, the main purpose of this article is to describe the current concern of the extra pulmonary complications that were caused due to COVID-19 and also to improve the management and diagnosis of these patients

ENDOVASCULARAPPROACHES TOACUTE ISCHEMIC STROKE- INDIAN PERSPECTIVE

Aim: To review literature about endovascular approaches to acute ischemic stroke and provide Indian perspective about managing these cases. Brief Summary: In acute ischemic stroke cases, intravenous thrombolysis (IVT) with altepase within 4.5 hours has been the standard of care. Due to certain limitations of IVT, in pooled patientlevel data from 5 trials (HERMES [Highly Effective Reperfusion Evaluated in Multiple Endovascular Stroke Trials], which included the 5 trials MR CLEAN, ESCAPE, REVASCAT, SWIFT PRIME, and EXTEND-IA), mechanical thrombectomy (MT) is indicated for patients with acute ischemic stroke due to a large artery occlusion (LVO) in the anterior circulation who can be treated within 24 hours of the time last known to be well (ie, at neurologic baseline), regardless of whether they received intravenous alteplase for the same ischemic stroke event. The maximum benefit can be achieved within 6 hours of onset of symptoms. There are studies suggesting the benefit of MT in posterior circulation stroke as well as in distal arteries. We are going to review the methodology of endovascular techniques in brief alongwith Indian perspective on feasibility of this treatment approach in AIS. Conclusion: Mechnicalthrombectomy is certainly an effective modality of treatment in large vessel occlusion in anterior circulation within 24 hours. More awareness regarding the approach in India, can reduce the stroke morbidity and mortality in many of the cases in future

MOLECULAR HETEROGENEITY IN ACUTE PROMYELOCYTIC LEUKEMIA - A SINGLE CENTRE EXPERIENCE FROM INDIA

Atypical breakpoints and variant APL cases involving alternative chromosomal aberrations are seen in a small subset of acute promyelocytic leukemia (APL) patients. Over 7 different partner genes for RARA have been described. Although rare, these variants prove to be a diagnostic challenge and require combination of advanced cytogenetic and molecular techniques for accurate characterization. Heterogeneity occurs not only at the molecular level but also at clinico-pathological level influencing treatment response and outcome. In this case series we describe the molecular heterogeneity of APL seen in a single tertiary referral centre with a focus on seven variant APL cases from a single tertiary cancer center in India over a period of two and a half years. We discuss five cases with PLZF-RARA fusion and two novel PML-RARA variants, including a Bcr3 variant involving fusion of PML exon4 and RARA exon3 with an additional 40 nucleotides originating from RARA intron2, another involving exon 6 of PML and exon 3 of RARA with addition of 126 nucleotides, which mapped to the central portion of RARA intron 2  To the best of our knowledge this is the first of kind case series from India</jats:p

TB Risk Perceptions among Medical Residents at a Tertiary Care Center in India

Setting. Government tertiary health care center in India. Objective. To understand the perceptions of medical residents about their risk of developing TB in the workplace. Design. Cross-sectional study in which a semistructured questionnaire which included an open-ended question to assess their main concerns regarding TB in workplace was used to collect data. Results. Out of 305 resident doctors approached, 263 (94%) completed a structured questionnaire and 200 of these responded to an open-ended question. Daily exposure to TB was reported by 141 (64%) residents, 13 (5%) reported a prior history of TB, and 175 (69%) respondents were aware of TB infection control guidelines. A majority reported concerns about acquiring TB (78%) and drug-resistant TB (88%). The key themes identified were concerns about developing drug-resistant TB (n=100; 50%); disease and its clinical consequences (n=39; 20%); social and professional consequences (n=37; 19%); exposure to TB patients (n=32; 16%); poor infection control measures (n=27; 14%); and high workload and its health consequences (n=16; 8%). Conclusion. Though many resident doctors were aware of TB infection control guidelines, only few expressed concern about lack of TB infection control measures. Doctors need to be convinced of the importance of these measures which should be implemented urgently

Rheumatoid Arthritis: Severity Classification, Factors Responsible, Pathophysiology, Current and Herbal Treatment

Rheumatoid Arthritis is the autoimmune disorder occurs due to the change in life style, improper diet plans, smoking, excessive alcohol consumption etc. It generally affects the joints and creates swelling and severe pain in joints which leads to further destruction of bone and cartilages. Due to autoimmune responses the factors like Tumor Necrosis Factor-α, Interleukins-1 are introduced to synovial and synovial membrane which creates the swelling and pain. These factors further produce reactive oxygen species and inducing osteoclasts which destruct the bone and cartilages. Along with the drugs the several natural herbal treatments are also available for the treatment of rheumatoid arthritis. This includes varies medicinal plants form which acacia species is more potent and efficient. Acacia Senegal is the plant which blocks the receptors and decreases the level of tumor necrosis factor-α. Present work on rheumatoid arthritis mainly covers classification, factors responsible, pathophysiology, severity, current treatment and its drawbacks, herbal treatment and its benefits in treatment of Rheumatoid Arthritis

Tuberculosis (TB) Aftermath: study protocol for a hybrid type I effectiveness-implementation non-inferiority randomized trial in India comparing two active case finding (ACF) strategies among individuals treated for TB and their household contacts

Background : Approximately 7% of all reported tuberculosis (TB) cases each year are recurrent, occurring among people who have had TB in the recent or distant past. TB recurrence is particularly common in India, which has the largest TB burden worldwide. Although patients recently treated for TB are at high risk of developing TB again, evidence around effective active case finding (ACF) strategies in this population is scarce. We will conduct a hybrid type I effectiveness-implementation non-inferiority randomized trial to compare the effectiveness, cost-effectiveness, and feasibility of two ACF strategies among individuals who have completed TB treatment and their household contacts (HHCs). Methods : We will enroll 1076 adults (≥ 18 years) who have completed TB treatment at a public TB unit (TU) in Pune, India, along with their HHCs (averaging two per patient, n = 2152). Participants will undergo symptom-based ACF by existing healthcare workers (HCWs) at 6-month intervals and will be randomized to either home-based ACF (HACF) or telephonic ACF (TACF). Symptomatic participants will undergo microbiologic testing through the program. Asymptomatic HHCs will be referred for TB preventive treatment (TPT) per national guidelines. The primary outcome is rate per 100 person-years of people diagnosed with new or recurrent TB by study arm, within 12 months following treatment completion. The secondary outcome is proportion of HHCs < 6 years, by study arm, initiated on TPT after ruling out TB disease. Study staff will collect socio-demographic and clinical data to identify risk factors for TB recurrence and will measure post-TB lung impairment. In both arms, an 18-month “mop-up” visit will be conducted to ascertain outcomes. We will use the RE-AIM framework to characterize implementation processes and explore acceptability through in-depth interviews with index patients, HHCs and HCWs (n = 100). Cost-effectiveness will be assessed by calculating the incremental cost per TB case detected within 12 months and projected for disability-adjusted life years averted based on modeled estimates of morbidity, mortality, and time with infectious TB. Discussion : This novel trial will guide India’s scale-up of post-treatment ACF and provide an evidence base for designing strategies to detect recurrent and new TB in other high burden settings. Trial registration : NCT04333485, registered April 3, 2020. CTRI/2020/05/025059 [Clinical Trials Registry of India], registered May 6 2020.Research reported in this manuscript was supported by the National Institute of Allergy and Infectious Diseases (NIAID) of the National Institutes of Health(NIH) under award number R01AI143748. See funding documentation in Additional file3. The funding body does not have a role in the collection, analysis, and interpretation of data for TB Aftermath nor were they involved in writing this manuscript

Cohort for Tuberculosis Research by the Indo-US Medical Partnership (CTRIUMPH): protocol for a multicentric prospective observational study

INTRODUCTION: Tuberculosis disease (TB) remains an important global health threat. An evidence-based response, tailored to local disease epidemiology in high-burden countries, is key to controlling the global TB epidemic. Reliable surrogate biomarkers that predict key active disease and latent TB infection outcomes are vital to advancing clinical research necessary to ‘End TB’. Well executed longitudinal studies strengthening local research capacity for addressing TB research priorities and advancing biomarker discovery are urgently needed. METHODS AND ANALYSIS: The Cohort for Tuberculosis Research by the Indo-US Medical Partnership (CTRIUMPH) study conducted in Byramjee Jeejeebhoy Government Medical College (BJGMC), Pune and National Institute for Research in Tuberculosis (NIRT), Chennai, India, will establish and maintain three prospective cohorts: (1) an Active TB Cohort comprising 800 adults with pulmonary TB, 200 adults with extrapulmonary TB and 200 children with TB; (2) a Household Contact Cohort of 3200 adults and children at risk of developing active disease; and (3) a Control Cohort consisting of 300 adults and 200 children with no known exposure to TB. Relevant clinical, sociodemographic and psychosocial data will be collected and a strategic specimen repository established at multiple time points over 24 months of follow-up to measure host and microbial factors associated with (1) TB treatment outcomes; (2) progression from infection to active TB disease; and (3) Mycobacterium tuberculosis transmission among Indian adults and children. We anticipate CTRIUMPH to serve as a research platform necessary to characterise some relevant aspects of the TB epidemic in India, generate evidence to inform local and global TB control strategies and support novel TB biomarker discovery. ETHICS AND DISSEMINATION: This study is approved by the Institutional Review Boards of NIRT, BJGMC and Johns Hopkins University, USA. Study results will be disseminated through peer-reviewed journals and research conferences. FUNDING: NIH/DBT Indo-US Vaccine Action Programme and the Indian Council of Medical Research

Smoking, alcohol use disorder and tuberculosis treatment outcomes: A dual co-morbidity burden that cannot be ignored

BackgroundMore than 20% of tuberculosis (TB) disease worldwide may be attributable to smoking and alcohol abuse. India is the second largest consumer of tobacco products, a major consumer of alcohol particularly among males, and has the highest burden of TB globally. The impact of increasing tobacco dose, relevance of alcohol misuse and past versus current or never smoking status on TB treatment outcomes remain inadequately defined.MethodsWe conducted a multi-centric prospective cohort study of newly diagnosed adult pulmonary TB patients initiated on TB treatment and followed for a minimum of 6 months to assess the impact of smoking status with or without alcohol abuse on treatment outcomes. Smokers were defined as never smokers, past smokers or current smokers. Alcohol Use Disorder Identification Test (AUDIT) scores were used to assess alcohol misuse. The association between smoking status and treatment outcomes was assessed in univariate and multivariate random effects poisson regression models.ResultsOf 455 enrolled, 129 (28%) had a history of smoking with 94 (20%) current smokers and 35 (8%) past smokers. Unfavourable treatment outcomes were significantly higher among past and current smokers as compared to never smokers. Specifically, the risk of treatment failure was significantly higher among past smokers (aIRR = 2.66, 95% CI: 1.41-4.90, p = 0.002), recurrent TB among current smokers (aIRR = 2.94, 95% CI: 1.30-6.67, p = 0.010) and death among both past (2.63, 95% CI: 1.11-6.24, p = 0.028) and current (aIRR = 2.59, 95% CI: 1.29-5.18, p = 0.007) smokers. Furthermore, the combined effect of alcohol misuse and smoking on unfavorable treatment outcomes was significantly higher among past smokers (aIRR: 4.67, 95% CI: 2.17-10.02, pConclusionPast and current smoking along with alcohol misuse have combined effects on increasing the risk of unfavourable TB treatment outcomes. Innovative interventions that can readily address both co-morbidities are urgently needed

Effect of angiotensin-converting enzyme inhibitor and angiotensin receptor blocker initiation on organ support-free days in patients hospitalized with COVID-19

IMPORTANCE Overactivation of the renin-angiotensin system (RAS) may contribute to poor clinical outcomes in patients with COVID-19. Objective To determine whether angiotensin-converting enzyme (ACE) inhibitor or angiotensin receptor blocker (ARB) initiation improves outcomes in patients hospitalized for COVID-19. DESIGN, SETTING, AND PARTICIPANTS In an ongoing, adaptive platform randomized clinical trial, 721 critically ill and 58 non–critically ill hospitalized adults were randomized to receive an RAS inhibitor or control between March 16, 2021, and February 25, 2022, at 69 sites in 7 countries (final follow-up on June 1, 2022). INTERVENTIONS Patients were randomized to receive open-label initiation of an ACE inhibitor (n = 257), ARB (n = 248), ARB in combination with DMX-200 (a chemokine receptor-2 inhibitor; n = 10), or no RAS inhibitor (control; n = 264) for up to 10 days. MAIN OUTCOMES AND MEASURES The primary outcome was organ support–free days, a composite of hospital survival and days alive without cardiovascular or respiratory organ support through 21 days. The primary analysis was a bayesian cumulative logistic model. Odds ratios (ORs) greater than 1 represent improved outcomes. RESULTS On February 25, 2022, enrollment was discontinued due to safety concerns. Among 679 critically ill patients with available primary outcome data, the median age was 56 years and 239 participants (35.2%) were women. Median (IQR) organ support–free days among critically ill patients was 10 (–1 to 16) in the ACE inhibitor group (n = 231), 8 (–1 to 17) in the ARB group (n = 217), and 12 (0 to 17) in the control group (n = 231) (median adjusted odds ratios of 0.77 [95% bayesian credible interval, 0.58-1.06] for improvement for ACE inhibitor and 0.76 [95% credible interval, 0.56-1.05] for ARB compared with control). The posterior probabilities that ACE inhibitors and ARBs worsened organ support–free days compared with control were 94.9% and 95.4%, respectively. Hospital survival occurred in 166 of 231 critically ill participants (71.9%) in the ACE inhibitor group, 152 of 217 (70.0%) in the ARB group, and 182 of 231 (78.8%) in the control group (posterior probabilities that ACE inhibitor and ARB worsened hospital survival compared with control were 95.3% and 98.1%, respectively). CONCLUSIONS AND RELEVANCE In this trial, among critically ill adults with COVID-19, initiation of an ACE inhibitor or ARB did not improve, and likely worsened, clinical outcomes. TRIAL REGISTRATION ClinicalTrials.gov Identifier: NCT0273570