BackgroundFertility remains a controversial issue in women with systemic lupus erythematosus (SLE); it is largely preserved, though a subset experiences subfertility due to multiple interacting factors. Small studies on anti-mullerian hormone (AMH) as an ovarian reserve marker in SLE have yielded conflicting results; data on antral follicular count (AFC) and ovarian volume (OV) are sketchy. Potential ethno-geographic differences exist, but there is no data on ovarian reserve of Indian lupus patients. There is lack of clarity on the factors affecting ovarian reserve in SLE.MethodsIn this single-centre observational study, female SLE patients aged 18–45 years were tested for AMH, FSH, and estradiol at D2–D5 of menstrual cycle. Ultrasonographic assessment of AFC and OV was done in a subset. Age-specific nomograms of AMH and AFC of healthy fertile women were used for comparison. Proportion of patients with premature ovarian insufficiency (POI), early menopause, and those having low AMH (<1 ng/mL) were calculated. Clinico-immunological determinants of reduced ovarian reserve were identified through multivariable logistic regression.Results168 lupus women [mean age 27(6.4) years] were included. 93(55%) were married. 120(72%) had regular menstrual cycles. 3(1.8%) had POI (at 21, 22, and 37 years of age), while an additional two (1.2%) had early menopause at 41 and 44 years. 82(49%) were found to have low AMH. Comparison with age-specific nomograms showed 64% patients had AMH and 47% had AFC less than the corresponding tenth centile of healthy fertile women. Multivariable regression showed higher age [OR = 1.12(1.05–1.20), p = 0.001], active disease [OR = 3.87(1.56–9.62), p = 0.004], menstrual irregularities [OR = 4.56(1.95–10.65), p < 0.001], and anti-Ro60 positivity [OR = 1.89(0.92–3.88), p = 0.08] independently predicted reduced AMH. There was no association with organ involvement (including nephritis), disease duration, anti-dsDNA, anti-Sm, or aPL positivity, or prior CYC use.ConclusionsPrevalence of POI and early menopause in our study was found to be 1.8% and 1.2%, respectively. A high proportion (49%) of Indian SLE patients had evidence of low ovarian reserve in the absence of known risk factors. Higher age, active disease, menstrual irregularities, and anti-Ro60 positivity were found to be independently associated with diminished ovarian reserve. No association was found with prior CYC use, nephritis, or antiphospholipid antibodies.

We observed a high proportion of proteins in pathogenic Mycobacterium species that can potentially undergo liquid-liquid phase separation (LLPS) mediated biomolecular condensate formation, compared to nonpathogenic species. These proteins mainly include the PE-PPE and PE-PGRS families of proteins that have nucleic acid and protein-protein binding functions, typical of LLPS proteins. We also mapped identified LLPS proteins in M. tuberculosis (M.tb) drug-resistant databases PubMLST and TBProfiler, based upon the WHO 2023 catalogue of resistance-associated mutations. High sequence conservation of LLPS-associated proteins in various multiple drug-resistant M.tb isolates points to their potentially important role in virulence and host-pathogen interactions during pathogenic evolution. This analysis provides a perspective on the role of protein phase separation in the evaluation of M.tb pathogenesis and offers avenues for future research aimed at developing innovative strategies to combat M.tb infection.

Background & objectives Pulmonary rehabilitation (PR) has been extensively studied and proven beneficial in various respiratory conditions such as chronic obstructive pulmonary disease (COPD) and interstitial lung disease (ILD). Individuals with post-tuberculosis lung disease (P-TBLD) have limited exercise tolerance and a significant disability affecting daily living, much like those with COPD. Hence, they appear to be good candidates for PR. This study aimed to determine the effectiveness of an outpatient PR protocol on functional exercise capacity and health-related quality of life (HRQOL) in individuals with P-TBLD. Furthermore, the effectiveness of adherence to the PR protocol among the participants as well as identifying the gaps and barriers in accessing PR were also determined. Methods This is a multicentric pre- and post-interventional study conducted across five centres in India. 260 individuals with P-TBLD were included if they could complete more than 80 per cent of the physiotherapist’s training sessions at the time of enrollment had previously received treatment for pulmonary tuberculosis and were negative for acid fast bacilli (AFB) on sputum examination. Individuals were excluded if they had preexisting lung disease other than P-TBLD or suffered from any mental, neurological, musculoskeletal, or unstable cardiovascular disease that could impair their performance during the exercise training sessions. Pre- and post-intervention assessments included clinical symptoms, exercise intolerance, pulmonary function test (PFT), 6-minute walk test (6MWT), muscle strength testing, and St. George Respiratory Questionnaire (SGRQ) score for HRQOL. Participants received PR training at first visit in OPD and were advised to follow it at home and telephonic follow up was done for a duration of 12 wk. Results Out of the 260 participants who were enrolled, 246 patients completed the post-intervention evaluation following 12 wk of the PR protocol. Clinical parameters, the 6MWT, the functional balance test, and the muscle strength test all showed significant improvement after PR. Significant improvement was observed across all domains of the SGRQ score. Pulmonary function measures showed significant improvement in FEV1 and FVC parameters post intervention. Interpretation & conclusions This study provides compelling evidence that PR is beneficial for post-TB patient, leading to notable improvements in the exercise capacity, symptom management as well as the overall quality of life. The findings support the implementation of PR protocol on a larger scale within national health frameworks, particularly in countries with high TB prevalence. By integrating PR into the National Tuberculosis Elimination Programme, it is possible to offer a comprehensive care approach that sets standard indicators for the surveillance of P-TBLD and addresses the long-term health needs of TB survivors.

There has been an increase in understanding of the burden of sleep disordered breathing among patients with interstitial lung disease (ILD). This study aimed to compute the prevalence of obstructive sleep apnea hypopnea syndrome (OSAHS) among ILD patients without any traditional risk factors for OSAHS. ILD patients were recruited and underwent anthropometric evaluation, pulmonary function tests and overnight polysomnography. Sleep quality was assessed using Pittsburgh sleep quality index. Patients with body mass index > 30.0 kg/m2 and other conventional risk factors of OSAHS were excluded. Thirty patients constituted the study group with 11 males and 19 females. Mean age of population was 47.1 ± 11.8 years and median BMI was 24.1 kg/m2. Poor sleep quality was reported by 83.3

Extra-pulmonary tuberculosis (EPTB) can affect any organ of the body, producing a wide variety of clinical manifestations that make the diagnosis and treatment of EPTB challenging. The optimum treatment varies depending on the site of EPTB, its severity, and response to treatment. There is often uncertainty about the best management practices, with a significant departure from national guidelines. This study aims to identify gaps and barriers in adhering to the national guidelines for the diagnosis and treatment of EPTB. We included 433 patients having EPTB and followed up at predefined intervals of 2 months, 6 months, 9 months, and 12 months. Questionnaire-based interviews of the treating physician and the patients in different departments were conducted. For confirmatory diagnosis, heavy dependence on clinical-radiological diagnosis without microbiological support was observed, which is a deviation from National Tuberculosis Elimination Programme (NTEP) guidelines and raises concerns about the potential for misdiagnosis and overtreatment. Apart from patient delays, long health system delays in EPTB were observed. The median patient delay, health system delay, and total treatment delay times were 4.2, 4, and 10.1 weeks, respectively. To enhance EPTB diagnosis and management, there is a pressing need for improved access to microbiological testing, enhanced physician training on adherence to NTEP guidelines, and greater utilisation of imaging and histopathological techniques.

Background Studies have reported estimates of the economic and health burden of COPD. They have been limited largely to current-day estimates or relatively short-term future projections. Research Question How will the regional and global economic and health burden of COPD evolve from 2025 to 2050, considering trends in COPD risk factors and an expanding population? Study Design and Methods To project the economic and health burden of COPD to 2050, an open cohort Markov model was developed. COPD costs were stratified by age, sex, and smoking status, and distributions of COPD severity grades were modeled based on global trends in smoking status, household air pollution, particulate matter ≤ 2.5 μm in diameter, and ozone. Direct costs, indirect costs, and the number of COPD exacerbations were projected to 2050. Data on the historic economic and health burden of COPD were obtained from the Global Burden of Disease (GBD) database, World Health Organization, and a recent meta-analysis. COPD risk factor data were obtained from the GBD database. Results By 2050, the global direct costs attributable to COPD are projected to be $24.35 trillion cumulatively ($3.89 trillion in 2025). Global indirect costs are estimated to be $15.43 trillion cumulatively by 2050 ($2.50 trillion in 2025), and 15.60 billion COPD exacerbations are projected to occur within that same period (2.28 billion in 2025). Interpretation To mitigate the substantial projected economic and health burden of COPD, it is essential to focus on prevention by reducing risk factors such as smoking and air pollution. Additionally, health care policy reforms can improve access to effective treatments, and innovative approaches can enhance patient outcomes.

BACKGROUND:Abdominal bloating is a common complaint in patients with functional and organic bowel disease. Rifaximin, a nonabsorbable antibiotic, has been tried for the treatment of this disease. We performed a systematic review and meta-analysis to study the efficacy of rifaximin in abdominal bloating and distension in patients with functional gastrointestinal disorders (FGID). METHODS:We accessed 4 databases (MEDLINE, Embase, SCOPUS, and Web of Science) to identify randomized placebo-controlled trials that utilized rifaximin in FGID. We excluded observational studies, those including patients with organic bowel disorders such as inflammatory bowel diseases, or those in which rifaximin was given for other indications, such as hepatic encephalopathy. RESULTS:A total of 1426 articles were available, of which 813 articles were screened after removing duplicates and 34 articles were selected for full-text review. Finally, 10 trials (3326 patients) were included. Rifaximin was administered in doses ranging from 400 to 1650 mg per day for 1 to 2 weeks. Rifaximin therapy led to a higher likelihood of improvement in symptoms of bloating (44.6% vs. 34.6%, RR 1.22, 95% CI 1.11, 1.35; n=2401 patients) without significant heterogeneity. However, daily doses less than 1200 mg/day were similar to placebo ( P =0.09). Bloating was quantified subjectively in 7 studies, and rifaximin led to a greater reduction in bloating scores compared with placebo (standardized mean difference -0.3, 95% CI -0.51, -0.1, P =0.04) but carried significant heterogeneity ( I2 =61.6%, P =0.01). CONCLUSIONS:Rifaximin therapy is associated with an increased likelihood of improvement in bloating and distension, as well as reduces the subjective severity of these symptoms in patients with FGID.

Background: Obstructive sleep apnea (OSA) is very common in obese patients. However, why some obese patients have severe OSA while others do not is unclear. Research is limited regarding which structures contribute to upper airway narrowing, especially in Asian patients where bony restrictions is thought to be important. Methods: Nineteen consecutive patients with BMI >= 35 kg/m2, and newly diagnosed with OSA based on overnight polysomnography were studied using non-contrast magnetic resonance imaging (MRI) of the upper airway during wakefulness. Results: Patients were divided into two groups, one with severe OSA comprising 11 patients and one without severe OSA having 8 patients. The retro-palatal airway was narrowest in both groups. Patients with severe OSA had a significantly narrower retroglossal airway (0.99 +/- 0.48 cm2 vs 2.61 +/- 2.02 cm2, p = 0.02), primarily due to a narrower anteroposterior diameter at this level (p = 0.03). The tongue volume (p = 0.91), lateral pharyngeal wall volume (p = 0.26), tongue length (p = 0.93), soft palate length (p = 0.13), and dynamic change of upper airway with inspiration (p = 0.31) were not significantly different between the two groups. Conclusions: While the retro-palatal airway is equally narrow in both groups of patients, patients with severe OSA also have a significantly narrower retro-glossal airway. This finding could represent either a generalized reduction in airway area in whole of the oropharynx or multiple-level obstruction; probably aggravating upper airway collapse during sleep, predisposing some Asian obese patients to develop severe OSA.

Asthma and related respiratory symptoms are growing in India and urban cities are experiencing increasing traffic-related air pollution (TRAP) levels. Our study investigates the association between TRAP and respiratory symptoms, and unplanned visits made to general practitioner/ emergency department/hospital admission in children and adolescents; we also aimed to understand whether low greenspaces surrounding the schools impacted this association. Trucks passing near the child's residences were used as a surrogate marker for measuring exposure to heavy TRAP. Exposures to school neighbourhood characteristics such as distance from major roads, a major source of TRAP, and industries were studied and the Normalized Difference Vegetation Index (NDVI) was used to measure greenspaces at 100 m and 200 m. Results showed no relationship between TRAP exposures and the odds of unplanned visits to general practitioners/emergency department /hospital admissions in young children; however, adolescents experienced increased risk. TRAP-related characteristics and greenspaces (within 200 m) strongly

This case report presents an atypical manifestation of tuberculosis in a 21-year-old male who presented with multiple subcutaneous swellings in the bilateral heel, left elbow, and base of the left third finger for the previous 6 months. The patient also experienced loss of appetite and unintentional weight loss. Despite initial suspicion of bacterial abscesses, antibiotics did not lead to significant improvement. Further investigations revealed an elevated erythrocyte sedimentation rate and findings suggestive of osteomyelitis on imaging. Gene Xpert testing confirmed multidrug-resistant Mycobacterium tuberculosis as the causative agent. The patient was prescribed a bedaquiline-based multidrug-resistant tuberculosis regimen, which resulted in reduction in swelling size. This report highlights the challenges in diagnosing and managing complex cases of primary multiple tubercular abscesses, especially with drug-resistant strains, emphasizing the importance of timely diagnosis and multidisciplinary management for successful outcomes.

While there is a renewed interest in the use of infrared imaging in the medical field owing to improvements in image acquisition and processing technologies, its utility in the diagnosis of diabetes mellitus on a large scale has not been adequately evaluated in previous studies. This was a multicenter, double-blind case–control trial across three centers in India which enrolled a total of 1095 adults in two groups—590 participants with diabetes and 505 healthy controls. The primary outcome was the difference in thermography readings between the two groups. The secondary outcomes included the correlation of thermography readings with HbA1C, considered the gold standard. The thermography readings at all seven sites were lower in people with diabetes as compared to the control group. However, this attained statistical significance across four sites—forehead (Δmean difference = 0·34, 95

Although closely associated with obesity, non-obese patients are also at significant risk of obstructive sleep apnea (OSA). Burden of OSA is grossly underestimated in non-obese Asian population. Most risk scores incorporate body mass index (BMI). This study tried to develop BMI-independent score to predict high-risk OSA in Indian population. This retrospective observational study analyzed anthropo-demographic, clinical and polysomnography data of 1898 patients. Coefficients of variables from multivariate regression analysis were used to create a BMI-independent score. Receiver operator characteristic curve analysis used to determine optimal cut-off; performance reported using sensitivity, specificity, predictive values and likelihood ratios. Mean age was 45.9 years; 73.0

BACKGROUND:Chronic pulmonary aspergillosis (CPA) is known to complicate patients with post-tubercular lung disease. However, some evidence suggests that CPA might co-exist in patients with newly-diagnosed pulmonary tuberculosis (P.TB) at diagnosis and also develop during therapy. The objective of this study was to confirm the presence of CPA in newly diagnosed P.TB at baseline and at the end-of-TB-therapy.MATERIALS AND METHODS:This prospective longitudinal study included newly diagnosed P.TB patients, followed up at third month and end-of-TB-therapy with symptom assessment, anti-Aspergillus IgG antibody and imaging of chest for diagnosing CPA.RESULTS:We recruited 255 patients at baseline out of which 158 (62%) completed their follow-up. Anti-Aspergillus IgG was positive in 11.1% at baseline and 27.8% at end-of-TB-therapy. Overall, proven CPA was diagnosed in 7% at baseline and 14.5% at the end-of-TB-therapy. Around 6% patients had evidence of aspergilloma in CT chest at the end-of-TB-therapy.CONCLUSIONS:CPA can be present in newly diagnosed P.TB patients at diagnosis and also develop during anti-tubercular treatment. Patients with persistent symptoms or developing new symptoms during treatment for P.TB should be evaluated for CPA. Whether patients with concomitant P.TB and CPA, while receiving antitubercular therapy, need additional antifungal therapy, needs to be evaluated in future studies.

Background: Anal cancer is an uncommon cancer in the general population, with an average worldwide incidence of 1.9 per 100,000 men and women per year from 2017 to 2021. We conducted an observational study on HIV-infected males who attended the ART clinic at AIIMS New Delhi to study the prevalence of anal cytopathological abnormalities as well as anal HPV nucleic acid, along with a risk factor assessment for the same. Methods: Participants’ inclusion criteria encompassed HIV-positive male patients over the age of 18 years who were attending the ART clinic. Following this, an anal cytopathological sample was collected for each participant. Results: Of these 65 samples, 8 (12.3

RNA viruses continue to remain a clear and present threat for potential pandemics due to their rapid evolution. To mitigate their impact, we urgently require antiviral agents that can inhibit multiple families of disease-causing viruses, such as arthropod-borne and respiratory pathogens. Potentiating host antiviral pathways can prevent or limit viral infections before escalating into a major outbreak. Therefore, it is critical to identify broad-spectrum antiviral agents. We have tested a small library of innate immune agonists targeting pathogen recognition receptors, including TLRs, STING, NOD, Dectin and cytosolic DNA or RNA sensors. We observed that TLR3, STING, TLR8 and Dectin-1 ligands inhibited arboviruses, Chikungunya virus (CHIKV), West Nile virus (WNV) and Zika virus, to varying degrees. Cyclic dinucleotide (CDN) STING agonists, such as cAIMP, diABZI, and 2',3'-cGAMP, and Dectin-1 agonist scleroglucan, demonstrated the most potent, broad-spectrum antiviral function. Comparative transcriptome analysis revealed that CHIKV-infected cells had larger number of differentially expressed genes than of WNV and ZIKV. Furthermore, gene expression analysis showed that cAIMP treatment rescued cells from CHIKV-induced dysregulation of cell repair, immune, and metabolic pathways. In addition, cAIMP provided protection against CHIKV in a CHIKV-arthritis mouse model. Cardioprotective effects of synthetic STING ligands against CHIKV, WNV, SARS-CoV-2 and enterovirus D68 (EV-D68) infections were demonstrated using human cardiomyocytes. Interestingly, the direct-acting antiviral drug remdesivir, a nucleoside analogue, was not effective against CHIKV and WNV, but exhibited potent antiviral effects against SARS-CoV-2, RSV (respiratory syncytial virus), and EV-D68. Our study identifies broad-spectrum antivirals effective against multiple families of pandemic potential RNA viruses, which can be rapidly deployed to prevent or mitigate future pandemics.