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Objectives: This systematic review and meta-analysis aimed at summarizing the evidence of efficacy and safety of rituximab in rheumatoid arthritis-related interstitial lung disease (RA-ILD)., Materials and Methods: PubMed and Embase databases were searched until June 22, 2022, to identify studies on RA-ILD treated with rituximab, confined to predefined inclusion and exclusion criteria. A systematic review and meta-analysis were performed on the included studies to assess the overall stabilization or improvement in ILD, changes in percent-predicted (%-predicted) forced vital capacity (FVC), and %-predicted diffusion capacity of lungs for carbon monoxide (DLCO) following rituximab therapy., Results: A total of 15 studies (4 prospective and 11 retrospective studies) were included, with a total of 314 patients. There were 105 (60.7%) females out of 173 subjects for whom sex details were available from seven studies. The overall pooled proportion of patients with stabilization or improvement in ILD was 0.88 [95% confidence interval (CI): 0.76-0.96, p=0.02]. Rituximab improved FVC from baseline by 7.50% (95% CI: 1.35-13.65; p=0.02, fixed effect). Similarly, rituximab improved DLCO by 6.39% (95% CI: 1.366-14.43; p=0.12, random-effect). Two retrospective studies reported reduced mortality with rituximab therapy compared to tumor necrosis factor-alpha inhibitors., Conclusion: Treatment with rituximab in RA-ILD was associated with a significant improvement in %-predicted FVC, as well as stabilization or improvement in ILD after one year of treatment., Competing Interests: Conflict of Interest: The authors declared no conflicts of interest with respect to the authorship and/or publication of this article., (Copyright © 2024, Turkish League Against Rheumatism.)

Tuberculosis (TB) remains a major global public health problem worldwide. Though Pulmonary TB (PTB) is mostly discussed, one in five cases of TB present are extrapulmonary TB (EPTB) that manifests conspicuous diagnostic and management challenges with respect to the site of infection. The diagnosis of EPTB is often delayed or even missed due to insidious clinical presentation, pauci-bacillary nature of the disease, and lack of laboratory facilities in the resource limited settings. Culture, the classical gold standard for the diagnosis of tuberculosis, suffers from increased technical and logistical constraints in EPTB cases. Other than culture, several other tests are available but their feasibility and effciacy for the detection of EPTB is still the matter of interest. We need more specific and precise test/s for the various forms of EPTB diagnosis which can easily be applied in the routine TB control program is required. A test that can contribute remarkably towards improving EPTB case detection reducing the morbidity and mortality is the utmost requirement. In this review we described the scenario of molecular and other noval methods available for laboratory diagnosis of EPTB, and also discussed the challenges linked with each diagnostic method. This review will make the readers aware of new emerging diagnostic techniques in the field of EPTB diagnosis. They can make an informed decision to choose the appropriate one according to the test availability, their clinical settings and financial considerations., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Abstract: Medical Thoracoscopy (MT) is commonly performed by respiratory physicians for diagnostic as well as therapeutic purposes. The aim of the study was to provide evidence-based information regarding all aspects of MT, both as a diagnostic tool and therapeutic aid for pulmonologists across India. The consensus-based guidelines were formulated based on a multistep process using a set of 31 questions. A systematic search of published randomized controlled clinical trials, open labelled studies, case reports and guidelines from electronic databases, like PubMed, EmBase and Cochrane, was performed. The modified grade system was used (1, 2, 3 or usual practice point) to classify the quality of available evidence. Then, a multitude of factors were taken into account, such as volume of evidence, applicability and practicality for implementation to the target population and then strength of recommendation was finalized. MT helps to improve diagnosis and patient management, with reduced risk of post procedure complications. Trainees should perform at least 20 medical thoracoscopy procedures. The diagnostic yield of both rigid and semirigid techniques is comparable. Sterile-graded talc is the ideal agent for chemical pleurodesis. The consensus statement will help pulmonologists to adopt best evidence-based practices during MT for diagnostic and therapeutic purposes., (Copyright © 2024 Copyright: © 2024 Indian Chest Society.)

Background: Mycobacterium w (Mw), an immunomodulator, resulted in better clinical status in severe coronavirus infectious disease 19 (COVID-19) but no survival benefit in a previous study. Herein, we investigate whether Mw could improve clinical outcomes and survival in COVID-19., Materials and Methods: In a multicentric, randomized, double-blind, parallel-group, placebo-controlled trial, we randomized hospitalized subjects with severe COVID-19 to receive either 0.3 mL/day of Mw intradermally or a matching placebo for three consecutive days. The primary outcome was 28-day mortality. The co-primary outcome was the distribution of clinical status assessed on a seven-point ordinal scale ranging from discharged (category 1) to death (category 7) on study days 14, 21, and 28. The key secondary outcomes were the change in sequential organ failure assessment (SOFA) score on days 7 and 14 compared to the baseline, treatment-emergent adverse events, and others., Results: We included 273 subjects (136 Mw, 137 placebo). The use of Mw did not improve 28-day survival (Mw vs. placebo, 18 [13.2%] vs. 12 [8.8%], P = 0.259) or the clinical status on days 14 (odds ratio [OR], 1.33; 95% confidence intervals [CI], 0.79-2.3), 21 (OR, 1.49; 95% CI, 0.83-2.7) or 28 (OR, 1.49; 95% CI, 0.79-2.8) between the two study arms. There was no difference in the delta SOFA score or other secondary outcomes between the two groups. We observed higher injection site reactions with Mw., Conclusion: Mw did not reduce 28-day mortality or improve clinical status on days 14, 21 and 28 compared to placebo in patients with severe COVID-19. [Trial identifier: CTRI/2020/04/024846]., (Copyright © 2024 Copyright: © 2024 Indian Chest Society.)

Introduction: The dysregulated host immune response in sepsis is orchestrated by peripheral blood leukocytes. This study explored the associations of the peripheral blood leukocyte subpopulations with early clinical deterioration and mortality in sepsis., Methods: We performed a prospective observational single-center study enrolling adult subjects with sepsis within 48 h of hospital admission. Peripheral blood flow cytometry was performed for the patients at enrolment and after 5 days. The primary outcome was to explore the association between various leukocyte subpopulations at enrolment and early clinical deterioration [defined as an increase in the sequential organ failure assessment (SOFA) score between enrolment and day 5, or death before day 5]. Other pre-specified outcomes explored associations of leukocyte subpopulations at enrolment and on day 5 with in-hospital mortality., Results: A total of 100 patients, including 47 with septic shock were enrolled. The mean (SD) age of the patients was 53.99 (14.93) years. Among them, 26 patients had early clinical deterioration, whereas 41 died during hospitalization. There was no significant association between the leukocyte subpopulations at enrolment and early clinical deterioration on day 5. On multivariate logistic regression, a reduced percentage of CD8 + CD25+ T-cells at enrolment was associated with in-hospital mortality [odds ratio (OR), 0.82 (0.70-0.97); p-value = 0.02]. A reduced lymphocyte percentage on day 5 was associated with in-hospital mortality [OR, 0.28 (0.11-0.69); p-value = 0.01]. In a post-hoc analysis, patients with "very early" deterioration within 48 h had an increased granulocyte CD64 median fluorescent intensity (MFI) [OR, 1.07 (1.01-1.14); p-value = 0.02] and a reduced granulocyte CD16 MFI [OR, 0.97 (0.95-1.00); p-value = 0.04] at enrolment., Conclusions: None of the leukocyte subpopulations showed an association with early clinical deterioration at day 5. Impaired lymphocyte activation and lymphocytopenia indicative of adaptive immune dysfunction may be associated with in-hospital mortality., Competing Interests: Declaration of Conflicting InterestsThe authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Background: This study was conducted with the objective of measuring the neutralizing and anti-receptor binding domain antibody levels against SARS-CoV-2 among laboratory-confirmed COVID-19 cases and exploring its long-term kinetics over a period of 1 year. Methods: One hundred laboratory-confirmed COVID-19 cases were recruited. Serum samples of the participants were collected within three months from the date of the positive COVID-19 report. The participants were prospectively followed up every three months for symptoms and the collection of blood samples for three additional rounds. The presence of anti-SARS-CoV-2 antibodies (IgA, IgG, and IgM antibodies), anti-receptor binding domain antibodies (anti-RBD), and neutralizing antibodies were measured. Findings: Median plaque reduction neutralization test (PRNT) titers showed a rising trend in the first three rounds of follow-up. The quantitative anti-receptor binding domain ELISA (QRBD) values showed a declining trend in the initial three rounds. However, both the PRNT titers and QRBD values showed significantly higher values for the fourth round of follow-up. Total antibody (WANTAI) levels showed an increasing trend in the initial three rounds (statistically significant). Interpretation: Neutralizing antibodies showed an increasing trend. The anti-receptor binding domain antibodies showed a decreasing trend. Neutralizing antibodies and anti-RBD antibodies persisted in the majority.

Repeated serological testing tells about the change in the overall infection in a community. This study aimed to evaluate changes in antibody prevalence and kinetics in a closed cohort over six months in different sub-populations in India. The study included 10,000 participants from rural and urban areas in five states and measured SARS-CoV-2 antibodies in serum in three follow-up rounds. The overall seroprevalence increased from 73.9% in round one to 90.7% in round two and 92.9% in round three. Among seropositive rural participants in round one, 98.2% remained positive in round two, and this percentage remained stable in urban and tribal areas in round three. The results showed high antibody prevalence that increased over time and was not different based on area, age group, or sex. Vaccinated individuals had higher antibody prevalence, and nearly all participants had antibody positivity for up to six months., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Misra et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Lung cancer is one of the common cancers globally with high mortality and poor prognosis. Most cases of lung cancer are diagnosed at an advanced stage due to limited diagnostic resources. Screening modalities, such as sputum cytology and annual chest radiographs, have not proved sensitive enough to impact mortality. In recent years, annual low-dose computed tomography has emerged as a potential screening tool for early lung cancer detection, but it may not be a feasible option for developing countries. In this context, exhaled breath condensate (EBC) analysis has been evaluated recently as a noninvasive tool for lung cancer diagnosis. The breath biomarkers also have the advantage of differentiating various types and stages of lung cancer. Recent studies have focused more on microRNAs (miRNAs) as they play a key role in tumourigenesis by regulating the cell cycle, metastasis and angiogenesis. In this review, we have consolidated the current published literature suggesting the utility of miRNAs in EBC for the detection of lung cancer., Competing Interests: Conflict of interest: The authors have no conflicts of interest or disclosures., (Copyright ©ERS 2024.)

Background Cell-mediated immunity (CMI), or specifically T-cell-mediated immunity, is proven to remain largely preserved against the variants of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), including Omicron. The persistence of cell-mediated immune response in individuals longitudinally followed up for an extended period remains largely unelucidated. To address this, the current study was planned to study whether the effect of cell-mediated immunity persists after an extended period of convalescence or vaccination. Methods Whole blood specimens of 150 selected participants were collected and tested for Anti-SARS-CoV-2 Interferon-gamma (IFN-γ) response. Ex vivo SARS-CoV-2-specific interferon-gamma Enzyme-linked Immunospot (IFN-γ ELISpot) assay was carried out to determine the levels of virus-specific IFN-γ producing cells in individual samples. Findings Out of all the samples tested for anti-SARS-CoV-2 T-cell-mediated IFN-γ response, 78.4% of samples were positive. The median (interquartile range) spots forming units (SFU) per million levels of SARS-CoV-2-specific IFN-γ producing cells of the vaccinated and diagnosed participants was 336 (138-474) while those who were vaccinated but did not have the disease diagnosis was 18 (0-102); the difference between the groups was statistically significant. Since almost all the participants were vaccinated, a similar pattern of significance was observed when the diagnosed and the never-diagnosed participants were compared, irrespective of their vaccination status. Interpretations Cell-mediated immunity against SARS-CoV-2 persisted, irrespective of age and sex of the participant, for more than six months of previous exposure. Participants who had a history of diagnosed COVID-19 infection had better T-cell response compared to those who had never been diagnosed, in spite of being vaccinated., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2023, Misra et al.)

Idiopathic Pulmonary Fibrosis (IPF) is a progressively fatal and incurable disease characterized by the loss of alveolar structures, increased epithelial-mesenchymal transition (EMT), and aberrant tissue repair. In this study, we investigated the role of Nuclear Factor I-B (NFIB), a transcription factor critical for lung development and maturation, in IPF. Using both human lung tissue samples from patients with IPF, and a mouse model of lung fibrosis induced by bleomycin, we showed that there was a significant reduction of NFIB both in the lungs of patients and mice with IPF. Furthermore, our in vitro experiments using cultured human lung cells demonstrated that the loss of NFIB was associated with the induction of EMT by transforming growth factor beta (TGF-β). Knockdown of NFIB promoted EMT, while overexpression of NFIB suppressed EMT and attenuated the severity of bleomycin-induced lung fibrosis in mice. Mechanistically, we identified post-translational regulation of NFIB by miR-326, a miRNA with anti-fibrotic effects that is diminished in IPF. Specifically, we showed that miR-326 stabilized and increased the expression of NFIB through its 3'UTR target sites for Human antigen R (HuR). Moreover, treatment of mice with either NFIB plasmid or miR-326 reversed airway collagen deposition and fibrosis. In conclusion, our study emphasizes the critical role of NFIB in lung development and maturation, and its reduction in IPF leading to EMT and loss of alveolar structures. Our study highlights the potential of miR-326 as a therapeutic intervention for IPF. The schema shows the role of NFIB in maintaining the normal epithelial cell characteristics in the lungs and how its reduction leads to a shift towards mesenchymal cell-like features and pulmonary fibrosis. A In normal lungs, NFIB is expressed abundantly in the epithelial cells, which helps in maintaining their shape, cell polarity and adhesion molecules. However, when the lungs are exposed to factors that induce pulmonary fibrosis, such as bleomycin, or TGF-β, the epithelial cells undergo epithelial to mesenchymal transition (EMT), which leads to a decrease in NFIB. B The mesenchymal cells that arise from EMT appear as spindle-shaped with loss of cell junctions, increased cell migration, loss of polarity and expression of markers associated with mesenchymal cells/fibroblasts. C We designed a therapeutic approach that involves exogenous administration of NFIB in the form of overexpression plasmid or microRNA-326. This therapeutic approach decreases the mesenchymal cell phenotype and restores the epithelial cell phenotype, thus preventing the development or progression of pulmonary fibrosis., (© 2023. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)

Endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) is a standard-of-care modality for evaluating mediastinal lymph nodes and masses. The EBUS bronchoscope may also be introduced through the oesophageal route to perform sampling of accessible lesions, a technique described as transoesophageal bronchoscopic ultrasound-guided fine-needle aspiration (EUS-B-FNA). Because of the central oesophageal approach, EUS-B-FNA provides easy access to the left para-tracheal, subcarinal and para-oesophageal lymph nodes. In addition, the left adrenal gland (LAG) can also be imaged and sampled during the EUS-B-FNA procedure. In patients with suspected lung cancer, accurate staging is essential. Adrenal metastasis is relatively common and may often be a solitary metastatic site. We describe three cases where EUS-B-FNA was performed to safely sample the enlarged LAG in suspected lung cancer. We also review the literature on the performance characteristics of EUS-B-FNA for LAG aspiration.

Sarcoidosis is a systemic inflammatory disorder characterized by tissue infiltration due to mononuclear phagocytes and lymphocytes and associated noncaseating granuloma formation. Pulmonary sarcoidosis (PS) shares a number of clinical, radiological, and histopathological characteristics with that of pulmonary tuberculosis (PTB). Due to this, clinicians face issues in differentiating between PS and PTB in a substantial number of cases. There is a lack of any specific biomarker that can diagnose PS distinctively from PTB. We compared T-cell-based signature cytokines in patients with PS and PTB. In this study, we proposed a serum biomarker panel consisting of cytokines from cells: T helper (Th) 1 [interferon-gamma (IFN-γ); tumor necrosis factor-alpha (TNF-α)], Th9 [interleukin (IL)-9], Th17 [IL-17], and T regulatory (Treg) [IL-10; transforming growth factor-beta (TGF-β)]. We performed the principal component analysis that demonstrated that our serum cytokine panel has a significant predictive ability to differentiate PS from PTB. Our results could aid clinicians to improve the diagnostic workflow for patients with PS in TB endemic settings where the diagnosis between PS and PTB is often ambiguous., (© 2023 Wiley-VCH GmbH.)

Background COVID-19 has spread as two distinct surges of cases in many countries. Several countries have reported differences in disease severity and mortality in the two waves. Objective Compare the in-hospital mortality in the two COVID-19 waves at a tertiary care hospital in India. Methods We conducted a retrospective data collection. Distinct periods of surges in cases and admissions were defined as the first wave spanning from March 2020 to December 2020 and the second wave from April 2021 to June 21, 2021. The primary outcome of this study was to compare mortality rates in terms of total hospital mortality rate (TMR) and case fatality rate (CFR). Results Mortality rates of wave 2 were approximately 10 times that of wave 1 (TMR of 20.3% in wave 2 versus 2.4% in wave 1 and CFR of 1.5% versus 17.7% in wave 1 and 2, respectively). Mortalities in wave 2 had a larger proportion of severe disease at presentation, faster progression of symptoms to death, and more patients without any chronic comorbid condition dying due to the direct effect of COVID-19 acute respiratory distress syndrome (ARDS). Conclusion Our data matches the worldwide reported pooled hospital mortality figures and shows the comparative difference in disease severity between the two waves., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2023, Vig et al.)

Background: Chronic obstructive pulmonary disease (COPD) is an inflammatory disorder and has been proposed to have an imbalance between pro-inflammatory and anti-inflammatory factors., Methods: This study was conducted on 41 participants {18 COPD patients (smokers, COPD S ( n = 9); reformed smokers, COPD RS ( n = 9)) and 23 controls (non-smokers, CNS ( n = 14); smokers, CS ( n = 9))}. Flow cytometry was used to identify circulatory immune cells and correlated with serum cytokines., Results: On comparison, significantly lower frequency of CD3+ T cells were observed in COPD S as compared to CNS ( p < 0.01) and CS ( p < 0.01); CD4+ T cells were lower in COPD S ( p < 0.05), COPD RS ( p < 0.05) and CNS ( p < 0.01) as compared to CS. CD8+ T cells were elevated in COPD S as compared to CS ( p < 0.05). Lower frequency of cDCs were observed in COPD S as compared to CS ( p < 0.05) and COPD RS as compared to CNS ( p < 0.01) and CS ( p < 0.01). Lower frequency of pDCs were observed in COPD RS as compared to COPD S ( p < 0.05), CNS ( p < 0.05) and CS ( p < 0.01). Lower frequency of Tregs was observed in COPD S as compared to CNS ( p < 0.05) and CS ( p < 0.05)., Conclusions: Characteristic changes observed indicate a significant impact of immune cells in the progression of the disease.

Background: Ensuring adequate patient comfort is crucial during bronchoscopy. Although lidocaine spray is recommended for topical pharyngeal anesthesia, the optimum dose of sprays is unclear. We compared 5 versus 10 sprays of 10% lidocaine for topical anesthesia during bronchoscopy., Methods: In this investigator-initiated, prospective, multicenter, randomized clinical trial, subjects were randomized to receive 5 (group A) or 10 sprays (group B) of 10% lidocaine. The primary objective was to compare the operator-rated overall procedure satisfaction between the groups., Results: Two hundred eighty-four subjects were randomized (143 group A and 141 group B). The operator-rated overall procedure satisfaction, VAS [mean (SD)] was similar between the groups [group A, 74.1 (19.9) and group B, 74.3 (18.5), P =0.93]. The VAS scores of patient-rated cough [group A, 32.5 (22.9) and group B, 32.3 (22.2), P =0.93], and operator-rated cough [group A, 29.8 (22.3) and group B, 26.9 (21.5), P =0.26] were also similar. The time to reach vocal cords, overall procedure duration, mean doses of sedatives, the proportion of subjects willing to return for a repeat procedure (if required), and complications were not significantly different. Subjects in group A received significantly less cumulative lidocaine (mg) [group A, 293.9 (11.6) and group B, 343.5 (10.6), P <0.001]., Conclusion: During bronchoscopy, topical anesthesia with 5 sprays of 10% lidocaine is preferred as it is associated with a similar operator-rated overall procedure satisfaction at a lower cumulative lidocaine dose compared with 10 sprays., Competing Interests: Disclosure: There is no conflict of interest or other disclosures., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)

Over the past decade, endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) has become an indispensable tool in the diagnostic armamentarium of the pulmonologist. As the expertise with EBUS-TBNA has evolved and several innovations have occurred, the indications for its use have expanded. However, several aspects of EBUS-TBNA are still not standardized. Hence, evidence-based guidelines are needed to optimize the diagnostic yield and safety of EBUS-TBNA. For this purpose, a working group of experts from India was constituted. A detailed and systematic search was performed to extract relevant literature pertaining to various aspects of EBUS-TBNA. The modified GRADE system was used for evaluating the level of evidence and assigning the strength of recommendations. The final recommendations were framed with the consensus of the working group after several rounds of online discussions and a two-day in-person meeting. These guidelines provide evidence-based recommendations encompassing indications of EBUS-TBNA, pre-procedure evaluation, sedation and anesthesia, technical and procedural aspects, sample processing, EBUS-TBNA in special situations, and training for EBUS-TBNA.

The COVID-19 pandemic has affected the world, leading to significant morbidity and mortality. Various meteorological parameters are considered essential for the viability and transmission of the virus. Multiple reports from various parts of the world suggest a correlation between the disease spread and air pollution severity. This study was carried out to identify the relationship between meteorological parameters, air pollution, and COVID-19 in New Delhi, one of the worst-affected states in India. We studied air pollution and meteorological parameters in New Delhi, India. We obtained data about COVID-19 occurrence, meteorological parameters, and air pollution indicators from various sources from April 1, 2020, until November 12, 2020. We performed correlational analysis and employed autoregressive distributed lag models to identify the relationship between COVID-19 cases, air pollution and meteorological parameters. We found a significant impact of particulate matter (PM) 2.5, PM10, and meteorological parameters on COVID-19. There was a significant positive correlation between daily COVID-19 cases and COVID-19-related deaths with PM2.5 and PM10 levels. Increasing temperature and wind speed were associated with a reduction in the number of cases, while increasing humidity was associated with increased cases. This study demonstrated a significant association between PM2.5 and PM10 and daily COVID-19 cases and COVID-19-related mortality. This knowledge will likely help us prepare well for the future and implement air pollution control measures for other airborne disease epidemics.

Competing Interests: There is no conflicts of interest.

Competing Interests: All authors declare no conflicts of interest. No significant funding was received for this work.

The diagnosis of pediatric tuberculosis (TB) remains a major challenge, hence the evaluation of new tools for improved diagnostics is urgently required. We investigated the serum metabolic profile of children with culture-confirmed intra-thoracic TB (ITTB) (n = 23) and compared it with those of non-TB controls (NTCs) (n = 13) using proton NMR spectroscopy-based targeted and untargeted metabolomics approaches. In targeted metabolic profiling, five metabolites (histidine, glycerophosphocholine, creatine/phosphocreatine, acetate, and choline) differentiated TB children from NTCs. Additionally, seven discriminatory metabolites (N-α-acetyl-lysine, polyunsaturated fatty acids, phenylalanine, lysine, lipids, glutamate + glutamine, and dimethylglycine) were identified in untargeted metabolic profiling. The pathway analysis revealed alterations in six metabolic pathways. The altered metabolites were associated with impaired protein synthesis, hindered anti-inflammatory and cytoprotective mechanisms, abnormalities in energy generation processes and membrane metabolism, and deregulated fatty acid and lipid metabolisms in children with ITTB. The diagnostic significance of the classification models obtained from significantly distinguishing metabolites showed sensitivity, specificity, and area under the curve of 78.2%, 84.6%, and 0.86, respectively, in the targeted profiling and 92.3%, 100%, and 0.99, respectively, in the untargeted profiling. Our findings highlight detectable metabolic changes in childhood ITTB; however, further validation is warranted in a large cohort of the pediatric population., (© 2023 John Wiley & Sons Ltd.)

Lung cancer is one of the common malignancies with high mortality rate and a poor prognosis. Most lung cancer cases are diagnosed at an advanced stage either due to limited resources of infrastructure, trained human resources, or delay in clinical suspicion. Low-dose computed tomography has emerged as a screening tool for lung cancer detection but this may not be a feasible option for most developing countries. Electronic nose is a unique non-invasive device that has been developed for lung cancer diagnosis and monitoring response by exhaled breath analysis of volatile organic compounds. The breath-print have been shown to differ not only among lung cancer and other respiratory diseases, but also between various types of lung cancer. Hence, we postulate that the breath-print analysis by electronic nose could be a potential biomarker for the early detection of lung cancer along with monitoring treatment response in a resource-limited setting. In this review, we have consolidated the current published literature suggesting the use of an electronic nose in the diagnosis and monitoring treatment response of lung cancer., (Creative Commons Attribution license.)

Background and objective There is a dearth of studies on the clinical presentation of patients with post-pulmonary tuberculosis (PTB) sequelae and its impact on their quality of life (QoL). In light of this, we conducted this study to analyze the clinical profile and QoL in patients with post-PTB sequelae. Methods Patients with a history of treated PTB and evidence of radiological damage were enrolled prospectively from November 2018 till June 2020 to study their clinical profile and QoL as per the eligibility criteria. A detailed clinical history was taken along with posteroanterior-view chest X-rays and CT scans of the thorax with bronchial angiography in patients with hemoptysis. QoL was assessed using the Hindi version of St. George's Respiratory Questionnaire (SGRQ) for which permission was obtained from the St. George's University of London. SGRQ scores were calculated using score calculation algorithms (Microsoft Excel-based) and missing data imputation as recommended by its developer. Results A total of 174 patients were included in the analysis. The analyzed population was relatively younger (mean age: 44.27 years) with BMIs leaning toward the lower side of normal (median: 19.6 kg/m²); the majority of the patients were males (59%) and non-smokers (77%). PTB had been diagnosed clinico-radiologically in the majority (68%) of patients with non-compliance to antitubercular treatment (ATT) being reported by only 9% of patients. Multiple courses of ATT were received by about one-third of patients, mainly on a clinico-radiologic basis. Systemic hypertension (HTN) (11%) and diabetes mellitus (DM) (9%) were the most common comorbidities. The most common symptom complex found was cough, expectoration, and dyspnea (n=102, 59%). At least one incidence of massive hemoptysis was reported by 20% of patients. Bronchial artery embolization (BAE) was performed for moderate to massive hemoptysis in 26% of patients with a success rate of >90%. One-fifth of the study participants required hospitalization for exacerbation of respiratory symptoms with more than half of these (59%) requiring ventilatory support. Health-related QoL was significantly impaired as reflected by a median SGRQ total score of 45.53. The most affected domain of QoL was the activity domain (mean score: 45.47). Females had worse QoL as compared to males (p=0.0062), and so did underweight patients (p=0.048). The prolonged duration of the illness also significantly impaired the QoL (p<0.001, r=0.313). Conclusion The sequelae of PTB are under-recognized even among physicians and are frequently misdiagnosed as active PTB. The QoL is more severely affected due to residual damage. This study highlights the clinical profile of this patient population and underscores the need to recognize post-PTB sequelae as a separate entity. An important remedy to mitigate its long-term consequences is its inclusion and recognition in national and international TB guidelines to facilitate its early identification and promote further research to address its evidence-based management., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2023, Thoker et al.)

Severe acute respiratory syndrome coronavirus 2 disease (COVID-19) has caused more than 6 million deaths globally. Understanding predictors of mortality will help in prioritizing patient care and preventive approaches. This was a multicentric, unmatched, hospital-based case-control study conducted in nine teaching hospitals in India. Cases were microbiologically confirmed COVID-19 patients who died in the hospital during the period of study and controls were microbiologically confirmed COVID-19 patients who were discharged from the same hospital after recovery. Cases were recruited sequentially from March 2020 until December-March 2021. All information regarding cases and controls was extracted retrospectively from the medical records of patients by trained physicians. Univariable and multivariable logistic regression was done to assess the association between various predictor variables and deaths due to COVID-19. A total of 2,431 patients (1,137 cases and 1,294 controls) were included in the study. The mean age of patients was 52.8 years (SD: 16.5 years), and 32.1% were females. Breathlessness was the most common symptom at the time of admission (53.2%). Increasing age (adjusted odds ratio [aOR]: 46-59 years, 3.4 [95% CI: 1.5-7.7]; 60-74 years, 4.1 [95% CI: 1.7-9.5]; and ≥ 75 years, 11.0 [95% CI: 4.0-30.6]); preexisting diabetes mellitus (aOR: 1.9 [95% CI: 1.2-2.9]); malignancy (aOR: 3.1 [95% CI: 1.3-7.8]); pulmonary tuberculosis (aOR: 3.3 [95% CI: 1.2-8.8]); breathlessness at the time of admission (aOR: 2.2 [95% CI: 1.4-3.5]); high quick Sequential Organ Failure Assessment score at the time of admission (aOR: 5.6 [95% CI: 2.7-11.4]); and oxygen saturation < 94% at the time of admission (aOR: 2.5 [95% CI: 1.6-3.9]) were associated with mortality due to COVID-19. These results can be used to prioritize patients who are at increased risk of death and to rationalize therapy to reduce mortality due to COVID-19.

Background: Transbronchial lung cryobiopsy (TBLC) is frequently described for the diagnosis of diffuse parenchymal lung diseases (DPLD). A few studies have reported transbronchial cryobiopsy for the diagnosis of peripheral pulmonary lesions (PPL...s). We aimed to study the utility and safety of transbronchial cryobiopsy for the diagnosis of PPL...s., Methods: We performed a systematic search of the PubMed and Embase databases to extract the relevant studies. We then performed a meta-analysis to calculate the diagnostic yields of transbronchial cryobiopsy and bronchoscopic forceps biopsy., Results: Following a systematic search, we identified nine relevant studies (300 patients undergoing cryobiopsy). All used Radial Endobronchial Ultrasound (R-EBUS) for PPL localization. The pooled diagnostic yield of transbronchial cryobiopsy was 77% (95% CI, 71%...84%) (I^2=38.72%, p=0.11). The diagnostic yield of forceps biopsy was 72% (95% CI, 60%...83%) (I^2=78.56%, p<0.01). The diagnostic yield of cryobiopsy and forceps biopsy was similar (RR 1.05, 95% CI 0.96...1.15), with a 5% risk difference for diagnostic yield (95% CI, ...6% to 15%). There was significant heterogeneity (I^2=57.2%, p=0.017), and no significant publication bias. One severe bleeding and three pneumothoraxes requiring intercostal drain (ICD) placement (major complication rate 4/122, 1.8%) were reported with transbronchial cryobiopsy., Conclusions: R-EBUS guided transbronchial cryobiopsy is a safe and efficacious modality. The diagnostic yields of TBLC and forceps biopsy are similar. More extensive multicentre randomized trials are required for the further evaluation and standardization of transbronchial cryobiopsy for PPL...s., (Copyright © 2021 Sociedade Portuguesa de Pneumologia. Published by Elsevier España, S.L.U. All rights reserved.)

Background: Ultrasonographic characteristics may help differentiate between benign and malignant lymph nodes during endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA). There is limited data on the utility of various ultrasonographic lymph node features to differentiate between malignant and tuberculous mediastinal lymphadenopathy., Methods: We studied the various EBUS ultrasonographic lymph node characteristics (size, shape, margins, heterogeneous echotexture, calcification, central hilar structure, lymph node conglomeration, central intranodal vessel, and coagulation necrosis sign) from our available EBUS-TBNA database., Results: We extracted 1086 subjects [547 with tuberculosis (TB) and 539 with malignant diagnosis]. Comparing the 2 groups (multivariate analysis), presence of central hilar structure (8.2% vs. 2.6%), coagulation necrosis sign (37.5% vs. 13.7%), lymph node conglomeration (30.5% vs. 7.2%), calcification (5.1% vs. 1.5%), and distinct margins (83.5% vs. 69.8%), were significantly more common in TB ( P <0.05). On the other hand, malignant lymph nodes were larger and more likely to show the presence of a central intranodal vessel (20% vs. 15.8%, P =0.04, multivariate analysis). The absence of lymph node conglomeration had the highest overall diagnostic accuracy (0.61) for the differentiation between malignant and tuberculous lymph nodes., Conclusion: Sonographic lymph node characteristics may help differentiate malignant and tuberculous mediastinal lymphadenopathy. Contrary to previously published literature, we observed coagulation necrosis sign, heterogeneous echotexture and absent central intranodal vessel, more commonly in TB than malignant nodes. These findings from a TB endemic setting are different from other settings, where the prevalence of lung cancer is high in patients undergoing EBUS-TBNA., Competing Interests: Disclosure: There is no conflict of interest or other disclosures., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)

Background: Healthcare-associated infections (HAIs) are one of the most common adverse events in patient care that account for substantial morbidity and mortality. We evaluate the existing Infection Prevention and Control (IPC) practices in hospitals participating in the nationally representative HAI Surveillance network., Methods: This cross-sectional survey was conducted in 23 hospitals across 22 states of India from October-2015 to September-2018 in the HAI surveillance network. The World Health Organization (WHO) IPC core components assessment tool for health-care facility level (IPCAT-H) was adapted from IPC assessment tool developed by US Centers for Disease Control and Prevention (US CDC) under the Epidemiology and Laboratory Capacity (ELC) Infection Control Assessment and Response (ICAR) Program. Mann-Whitney U test was used to calculate the significant difference between scores (P < .05)., Results: Amongst the participating hospitals, 7 were private sectors and 16 were public health care facilities. Infection IPCAT-H average score per multimodal strategy was less than 50% for programmed IPC activities (45.7); implementation of health care workers (HCWs) immunization programme (43.5%); monitoring and evaluation component (38.30%)., Conclusions: There is potential for improvement in Human Resources, Surveillance of HAIs as well as Monitoring and Evaluation components., (Copyright © 2022 Association for Professionals in Infection Control and Epidemiology, Inc. Published by Elsevier Inc. All rights reserved.)

Aim: Globally, the incidence of lung cancer amongst women appears to be increasing. We aimed to compare the socio-epidemiological and clinical characteristics of lung cancer amongst men and women from a large cohort at a tertiary care hospital in Northern India., Methods: Records of patients diagnosed with lung cancer between January 2008 and March 2020 were reviewed. Baseline epidemiological data, clinical characteristics, histologic profiles, treatment administered, and survival were compared between males and females., Results: A total of 2054 male and 438 female patients were included in analysis. Compared to males, female patients were younger [median age, 56 vs. 60 years, P < 0.001)], less likely to be working, less educated beyond secondary level and less likely to be smokers (29.1% vs. 84.9%, P < 0.0001). No difference in baseline performance status was observed. Females were more frequently diagnosed with adenocarcinoma (54.2% vs. 30.2%, P = <0.0001), stage IV disease (70.8% vs. 63%, P = 0.001), and had higher rate of EGFR mutation (37.2% vs. 21.5%, P < 0.0001). There was no difference in the proportion of females receiving cancer-specific therapy. Multivariate Cox proportional hazards model revealed higher progression-free survival [median 9.17 vs. 7.23 months; P = 0.007] and overall survival [median 13.80 vs. 9.10 months respectively, P = 0.001] amongst females compared to males., Conclusion: Amongst a large cohort of lung cancer, females demonstrated several distinct and characteristic demographics as well as disease-related features, especially better survival outcomes., Competing Interests: None

Introduction: Quantitation of microRNAs secreted by lung cells can provide valuable information regarding lung health. Exhaled breath condensate (EBC) offers a non-invasive way to sample the secreted microRNAs, and could be used as diagnostic tools for lung cancer., Materials & Methods: EBC samples from twenty treatment-naïve patients with pathologically confirmed lung cancer and twenty healthy subjects were profiled for miRNAs expression. Selected microRNAs were further validated, using quantitative-PCR, in an independent set of 10 subjects from both groups., Results: A total of 78 miRNAs were found to be significantly upregulated in the EBC of lung cancer patients compared to the control group. Six of these 78 miRNAs were shortlisted for validation. Of these, miR-31-3p, let7i, and miR-449c were significantly upregulated, exhibited good discriminatory power., Discussion: Differential expression of miRNAs secreted by lung cells could be quantitated in EBC samples, and could be used as a potential non-invasive tool for early diagnosis of lung cancer., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background: Several methodological tests are available to detect SARS-CoV-2 antibody. Tests are mostly used in the aid of diagnosis or for serological assessment. No tests are fully confirmatory and have variable level of diagnostic ability. We aimed at assessing agreement with three serological tests: quantitative anti receptor binding domain ELISA (Q-RBD), qualitative ELISA (WANTAI SARS-CoV-2 Ab) and qualitative chemiluminescence assay (CLIA)., Methods: This study was a part of a large population based sero-epidemiological cohort study. Participants aged 1 year or older were included from 25 randomly selected clusters each in Delhi urban (urban resettlement colony of South Delhi district) and Delhi rural (villages in Faridabad district, Haryana). Three type of tests were applied to all the baseline blood samples. Result of the three tests were evaluated by estimating the total agreement and kappa value., Results: Total 3491 blood samples collected from March to September, 2021, out of which 1700 (48.7%) from urban and 1791 (51.3%) from rural. Overall 44.1% of participants were male. The proportion of sero-positivity were 78.1%, 75.2% and 31.8% by Wantai, QRBD and CLIA tests respectively. The total agreement between Wantai and QRBD was 94.5%, 53.1% between Wantai and CLIA, and 56.8% between QRBD and CLIA. The kappa value between these three tests were 0.84 (95% CI 0.80-0.87), 0.22 (95% CI 0.19-0.24) and 0.26 (95% CI 0.23-0.28)., Conclusions: There was strong concordance between Wantai and QRBD test. Agreement between CLIA with other two tests was low. Wantai and QRBD tests measuring the antibody to same S protein can be used with high agreement based on the relevant scenario., (© 2022. The Author(s).)

Competing Interests: There are no conflicts of interest.

Introduction: Elastography is a non-invasive tool that may allow differentiation between benign and malignant lymph nodes during endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA). In tuberculosis (TB) endemic areas, clinicoradiological features of mediastinal TB and sarcoidosis often overlap, rendering an accurate diagnosis challenging. There is interest in the identification of modalities to aid in this differentiation. There are currently no published data on the utility of EBUS-elastography in differentiating between TB and sarcoidosis., Methods: Subjects undergoing EBUS-TBNA were prospectively enrolled, and elastography features were observed. Subjects with definitive diagnosis of TB or sarcoidosis were enrolled. The elastography features recorded included the three-colour classification patterns and strain ratio., Results: We enrolled 96 subjects with a definitive diagnosis (53 with TB and 43 with sarcoidosis). Of the 27 patients in whom the lymph nodes were classified as type 1 on endobronchial ultrasound elastography colour pattern, 17 had a diagnosis of TB (62.9%), while 10 were sarcoidosis (37%). For type 2 lymph nodes, 20/45 (44.4%) were TB and 25/45 (55.6%) were sarcoidosis. Type 3 lymph nodes were TB in 16/24 (66.7%) and sarcoidosis in 8/24 (33.3%). In classifying type 1 as 'sarcoidosis' and Type 3 as 'tubercular', the sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and diagnostic accuracy were 48.5%, 55.6%, 66.7%, 37%, and 0.51, respectively. The strain ratio (Median [IQR]) was 1.29 (0.37-5.98) in TB and 2.10 (0.83-4.52) in sarcoidosis group (P = 0.48)., Conclusion: Ultrasound elastographic lymph node characteristics have a poor diagnostic utility to differentiate between TB and sarcoidosis during EBUS-TBNA., Competing Interests: None

Introduction: The small cell variant is a relatively uncommon but aggressive form of lung cancer. The present study aims to analyse the clinical characteristics, treatment outcomes and prognostic factors of an ambispectively enrolled large cohort of small cell lung cancer (SCLC) in the Indian population over a decade-long period., Materials and Methods: All patients diagnosed with SCLC between 2008 and 2020 at a tertiary care lung cancer clinic were included. The clinical details, demographics, details of investigations, treatment and survival outcomes were recorded and analysed., Results: A total of 361 patients were included. The majority were males (86.4%) with a mean (SD) age of 57.3 (12.3) years. Further, 34.9% were current smokers, with the median smoking index being 520 (interquartile range [IQR]: 260-1000). The majority had good performance status, that is, the Eastern Cooperative Oncology Group scale (ECOG) 0 or 1 (65%), and Karnofsky Performance Scale (KPS) ≥70 (85.9%). Also, 73.3% had extensive stage disease. The median time from symptom onset to definitive diagnosis was 91 days. Treatment details were available for 179 patients: chemotherapy only (n = 128), combined chemo-radiotherapy (n = 41) and radiotherapy only (n = 10). The median (IQR) progression-free survival (PFS) was 182 (94 to 306) days and the median (IQR) overall survival (OS) was 205 (94 to 429) days. On univariate analysis, factors that significantly affected survival included smoking index and performance status. However, on multivariate analysis, only the performance status significantly affected PFS, whereas none of these factors were significant for OS., Conclusions: SCLC predominantly affects males with a heavy smoking index. The diagnosis is usually made late; survival remains poor and is predominantly affected by the performance status., Competing Interests: None

Background: While long-term studies on the correlates of protection, vaccine effectiveness, and enhanced surveillance are awaited for SARS-CoV-2 vaccine, studies on breakthrough infections help understand the nature and course of this illness among vaccinated individuals and guide in public health preparedness. This study aims to compare the differences in the hospitalization outcomes SARS-CoV-2 infection of fully vaccinated individuals with with those of unvaccinated and partially vaccinated individuals., Materials and Methods: Single institution observational cohort study. This study compared the differences in clinical, biochemical parameters and the hospitalization outcomes of 53 fully vaccinated individuals with those of unvaccinated (1464) and partially vaccinated (231) individuals, among a cohort of 2,080 individuals hospitalized with SARS-CoV-2 infection. Descriptive statistics and propensity-score weighted multivariate logistic regression analysis adjusting for clinical and laboratory parameters were used to compare the differences and to identify factors associated with outcomes., Results: Completing the course of vaccination protected individuals from developing severe COVID-19 as evidenced by lower proportions of those with hypoxia, abnormal levels of inflammatory markers, requiring ventilatory support, and death compared to unvaccinated and partially vaccinated individuals. There were no differences in these outcomes among patients who received either vaccine type approved in India., Conclusions: Efforts should be made to improve the vaccination rates as a timely measure to prepare for the upcoming waves of this highly transmissible pandemic. Vaccination rates of the communities may also guide in the planning of the health needs and appropriate use of medical resources., Competing Interests: There are no conflicts of interest., (Copyright: © 2022 Indian Journal of Community Medicine.)

Background & Objectives: Studies assessing the spatial and temporal association of ambient air pollution with emergency room visits of patients having acute respiratory symptoms in Delhi are lacking. Therefore, the present study explored the relationship between spatio-temporal variation of particulate matter (PM) 2.5 concentrations and air quality index (AQI) with emergency room (ER) visits of patients having acute respiratory symptoms in Delhi using the geographic information system (GIS) approach., Methods: The daily number of ER visits of patients having acute respiratory symptoms (less than or equal to two weeks) was recorded from the ER of four hospitals of Delhi from March 2018 to February 2019. Daily outdoor PM 2.5 concentrations and air quality index (AQI) were obtained from the Delhi Pollution Control Committee. Spatial distribution of patients with acute respiratory symptoms visiting ER, PM 2.5 concentrations and AQI were mapped for three seasons of Delhi using ArcGIS software., Results: Of the 70,594 patients screened from ER, 18,063 eligible patients were enrolled in the study. Winter days had poor AQI compared to moderate and satisfactory AQI during summer and monsoon days, respectively. None of the days reported good AQI (<50). During winters, an increase in acute respiratory ER visits of patients was associated with higher PM 2.5 concentrations in the highly polluted northwest region of Delhi. In contrast, a lower number of acute respiratory ER visits of patients were seen from the 'moderately polluted' south-west region of Delhi with relatively lower PM 2.5 concentrations., Interpretation & Conclusions: Acute respiratory ER visits of patients were related to regional PM 2.5 concentrations and AQI that differed during the three seasons of Delhi. The present study provides support for identifying the hotspots and implementation of focused, intensive decentralized strategies to control ambient air pollution in worst-affected areas, in addition to the general city-wise strategies.

Purpose: With millions of people being affected by COVID-19, people living with post COVID-19 clinical symptoms (PCS) are expected to rise further. The primary aim of the study was to comprehensively assess self-reported PCS and its associated risk factors among beneficiaries of Hospital Employee Scheme of a tertiary healthcare institution in Delhi., Patients and Methods: An online cross-sectional study was conducted using a semi-structured questionnaire developed by employing nominal group technique among individuals aged 18 years and above who were novel SARS-CoV-2 positive from January to April 2021. Participants were telephoned first, before sending the online survey link. Socio-demographic data, information on PCS along with potential risk factors, pre-existing morbidities, vaccination status, severity of acute illness and management were collected between June and July 2021. PCS was presented as relative frequency; Chi-Square test and odds ratio; adjusted values were used to rule out any association between PCS and predictors., Results: In total, 773 of 1801 eligible participants responded to the survey (completion rate 42.9%), with a median age of 34 years (IQR 27-44). Males accounted for 56.4% and PCS was present in 33.2%. The most prevalent symptoms were fatigue (79.3%), arthralgia (33.4%), myalgia (29.9%), hair loss (28.0%), headache (27.2%), breathlessness (25.3%), and sleep disturbance (25.3%). The prevalence of PCS was reduced to 12.8% at 12 weeks. Female gender, older age, oxygen supplementation, severity of acute illness, and pre-existing co-morbidities were positively associated with PCS. Vaccination (second dose) reduced the odds of developing PCS by 39% compared to unvaccinated participants (aOR 0.61; 95% CI 0.40-0.96)., Conclusion: PCS affects almost all organ systems of the body, regardless of the severity of acute COVID-19 illness. Two doses of vaccine hel reduce the development of PCS., Competing Interests: The authors report no conflicts of interests in this work., (© 2022 Senjam et al.)

COVID-19-associated pulmonary mucormycosis (CAPM) remains an underdiagnosed entity. Using a modified Delphi method, we have formulated a consensus statement for the diagnosis and management of CAPM. We selected 26 experts from various disciplines who are involved in managing CAPM. Three rounds of the Delphi process were held to reach consensus (≥70% agreement or disagreement) or dissensus. A consensus was achieved for 84 of the 89 statements. Pulmonary mucormycosis occurring within 3 months of COVID-19 diagnosis was labelled CAPM and classified further as proven, probable, and possible. We recommend flexible bronchoscopy to enable early diagnosis. The experts proposed definitions to categorise dual infections with aspergillosis and mucormycosis in patients with COVID-19. We recommend liposomal amphotericin B (5 mg/kg per day) and early surgery as central to the management of mucormycosis in patients with COVID-19. We recommend response assessment at 4-6 weeks using clinical and imaging parameters. Posaconazole or isavuconazole was recommended as maintenance therapy following initial response, but no consensus was reached for the duration of treatment. In patients with stable or progressive disease, the experts recommended salvage therapy with posaconazole or isavuconazole. CAPM is a rare but under-reported complication of COVID-19. Although we have proposed recommendations for defining, diagnosing, and managing CAPM, more extensive research is required., Competing Interests: Declaration of interests AP received honoraria and lecture fees from Gilead Sciences, Pfizer (India), Intas Pharmaceuticals, Mylan (India), Bharat Serum Vaccine, and Cipla India. TS received lecture fees from Mylan (India), Cipla India, Merck Sharp & Dohme, Intas Pharmaceuticals, Pfizer (India), and Glenmark Pharmaceuticals. All other authors declare no competing interests., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Objectives: India introduced BBV152/Covaxin and AZD1222/Covishield vaccines in January 2021. We estimated the effectiveness of these vaccines against severe COVID-19 among individuals aged ≥45 years., Methods: We did a multi-centric, hospital-based, case-control study between May and July 2021. Cases were severe COVID-19 patients, and controls were COVID-19 negative individuals from 11 hospitals. Vaccine effectiveness (VE) was estimated for complete (2 doses ≥ 14 days) and partial (1 dose ≥ 21 days) vaccination; interval between two vaccine doses and vaccination against the Delta variant. We used the random effects logistic regression model to calculate the adjusted odds ratios (aOR) with a 95% confidence interval (CI) after adjusting for relevant known confounders., Results: We enrolled 1143 cases and 2541 control patients. The VE of complete vaccination was 85% (95% CI: 79-89%) with AZD1222/Covishield and 71% (95% CI: 57-81%) with BBV152/Covaxin. The VE was highest for 6-8 weeks between two doses of AZD1222/Covishield (94%, 95% CI: 86-97%) and BBV152/Covaxin (93%, 95% CI: 34-99%). The VE estimates were similar against the Delta strain and sub-lineages., Conclusion: BBV152/Covaxin and AZD1222/Covishield were effective against severe COVID-19 among the Indian population during the period of dominance of the highly transmissible Delta variant in the second wave of the pandemic. An escalation of two-dose coverage with COVID-19 vaccines is critical to reduce severe COVID-19 and further mitigate the pandemic in the country., (Copyright © 2022 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Amongst various manifestations of pulmonary aspergillosis, chronic pulmonary aspergillosis (CPA) is the most common. We conducted this study to identify different morphological forms of CPA, on computed tomography angiography (CTA), and to correlate these with clinical presentation, as well as, associated imaging features. The study design was cross-sectional, with a final sample size of 65 patients, recruited over a period of 2years from January 2017 to October 2018. Patients with past history of tuberculosis (TB), presenting with haemoptysis and found to have aspergilloma on computed tomography and lab tests were included in the study. All patients underwent CTA for evaluation of haemoptysis. Three morphological types of intracavitary aspergilloma on imaging were identified: type 1-nodular soft tissue along the cavity-wall, type-2 soft tissue density with multiple air lucencies and type-3 homogenous soft tissue opacity with air-crescent sign. Aspergilloma types were correlated with grade and duration of haemoptysis, associated imaging findings and vascularity score on CTA. Mean age of the patients was 40.97 +/- 13.69 years. As the type of aspergilloma changed from 1 to 3, there was a decrease in cavity wall thickness, peri-cavitary inflammation and vascularity. It is the type 1 and 2 aspergillomas, which caused more inflammation in the lungs, and hence recruited more abnormal vasculature. No significant correlation was found between haemoptysis severity and type of aspergilloma; type 3 aspergilloma however had longer duration of haemoptysis. In conclusion, the initial stages of formation of aspergilloma (type 1 and 2) cause more parenchymal inflammation and symptoms. The classical Monod sign is observed in the late stage of aspergilloma, since the peri-cavitary inflammation is reduced by then and thus the symptoms., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Objective: The majority of lung cancers are diagnosed at an advanced stage; the reasons for which are variable and unclear., Methods: Lung cancer patients were evaluated prospectively to quantify various timelines and establish reasons for delays. Timelines were defined as time intervals between symptom onset, first physician visit, first specialist visit, date of diagnosis and treatment., Results: A total 410 patients were included, majority having advanced disease. The median period for a first visit to a physician was 30 days (interquartile range [IQR] 20-90), 50 days (IQR 20-110) for referral to our centre, 23 days (IQR 14-33) to reach diagnosis, and 24 days (IQR 14.5-34) to initiate treatment. Administration ofanti-tuberculosis treatment further delayed referral to specialist centre. Treatment delays were related to performance status, disease stage and treatment type. On multivariate analysis, education and histology affected diagnosis delay and treatment delay. Treatment delay was less in those who received targeted therapy compared to chemotherapy. Various time delays did not affect the overall survival., Conclusion: Poor education status and inappropriate anti-tubercular treatment were primary factors associated with longer diagnostic delays. Creating disease awareness and high clinical suspicion are essential to overcome these lacunae in lung cancer care., (© 2022 John Wiley & Sons Ltd.)

Background: Studies on the extent to which long-term exposure to ambient particulate matter (PM) with aerodynamic diameter ≤ 2.5 μ m ( PM 2.5 ) contributes to adult mortality in India are few, despite over 99% of Indians being exposed to levels that the World Health Organization (WHO) considers unsafe., Objective: We conducted a retrospective cohort study within the Million Death Study (MDS) to provide the first-ever quantification of national mortality from exposure to PM 2.5 in India from 1999 to 2014., Methods: We calculated relative risks (RRs) by linking a total of ten 3-y intervals of satellite-based estimated PM 2.5 exposure to deaths 3 to 5 y later in over 7,400 small villages or urban blocks covering a total population of 6.8  million . We applied using a model-based geostatistical model, adjusted for individual age, sex, and year of death; smoking prevalence, rural/urban residency, area-level female illiteracy, languages, and spatial clustering and unit-level variation., Results: PM 2.5 exposure levels increased from 1999 to 2014, particularly in central and eastern India. Among 212,573 deaths at ages 15-69 y, after spatial adjustment, we found a significant RR of 1.09 [95% credible interval (CI): 1.04, 1.14] for stroke deaths per 10 - μ g / m 3 increase in PM 2.5 exposure, but no significant excess for deaths from chronic respiratory disease and ischemic heart disease (IHD), all nonaccidental causes, and total mortality (after excluding stroke). Spatial adjustment attenuated the RRs for chronic respiratory disease and IHD but raised those for stroke. The RRs were consistent in various sensitivity analyses with spatial adjustment, including stratifying by levels of solid fuel exposure, by sex, and by age group, addition of climatic variables, and in supplementary case-control analyses using injury deaths as controls., Discussion: Direct epidemiological measurements, despite inherent limitations, yielded associations between mortality and long-term PM 2.5 inconsistent with those reported in earlier models used by the WHO to derive estimates of PM 2.5 mortality in India. The modest RRs in our study are consistent with near or null mortality effects. They suggest suitable caution in estimating deaths from PM 2.5 exposure based on MDS results and even more caution in extrapolating model-based associations of risk derived mostly from high-income countries to India. https://doi.org/10.1289/EHP9538.

Introduction: As millions of people worldwide recover from COVID-19, a substantial proportion continue to have persistent symptoms, pulmonary function abnormalities, and radiological findings suggestive of post-COVID interstitial lung disease (ILD). To date, there is limited scientific evidence on the management of post-COVID ILD, necessitating a consensus-based approach., Areas Covered: A panel of experts in pulmonology and thoracic radiology was constituted. Key questions regarding the management of post-COVID ILD were identified. A search was performed on PubMed and EMBASE and updated till 1 March 2022. The relevant literature regarding the epidemiology, pathophysiology, diagnosis and treatment of post-COVID ILD was summarized. Subsequently, suggestions regarding the management of these patients were framed, and a consensus was obtained using the Delphi approach. Those suggestions which were approved by over 80% of the panelists were accepted. The final document was approved by all panel members., Expert Opinion: Dedicated facilities should be established for the care of patients with post-COVID ILD. Symptom screening, pulmonary function testing, and thoracic imaging have a role in the diagnosis. The pharmacologic and non-pharmacologic options for the management of post-COVID ILD are discussed. Further research into the pathophysiology and management of post-COVID ILD will improve our understanding of this condition.

Background: Health-care-associated infections (HAIs) cause significant morbidity and mortality globally, including in low-income and middle-income countries (LMICs). Networks of hospitals implementing standardised HAI surveillance can provide valuable data on HAI burden, and identify and monitor HAI prevention gaps. Hospitals in many LMICs use HAI case definitions developed for higher-resourced settings, which require human resources and laboratory and imaging tests that are often not available., Methods: A network of 26 tertiary-level hospitals in India was created to implement HAI surveillance and prevention activities. Existing HAI case definitions were modified to facilitate standardised, resource-appropriate surveillance across hospitals. Hospitals identified health-care-associated bloodstream infections and urinary tract infections (UTIs) and reported clinical and microbiological data to the network for analysis., Findings: 26 network hospitals reported 2622 health-care-associated bloodstream infections and 737 health-care-associated UTIs from 89 intensive care units (ICUs) between May 1, 2017, and Oct 31, 2018. Central line-associated bloodstream infection rates were highest in neonatal ICUs (>20 per 1000 central line days). Catheter-associated UTI rates were highest in paediatric medical ICUs (4·5 per 1000 urinary catheter days). Klebsiella spp (24·8%) were the most frequent organism in bloodstream infections and Candida spp (29·4%) in UTIs. Carbapenem resistance was common in Gram-negative infections, occurring in 72% of bloodstream infections and 76% of UTIs caused by Klebsiella spp, 77% of bloodstream infections and 76% of UTIs caused by Acinetobacter spp, and 64% of bloodstream infections and 72% of UTIs caused by Pseudomonas spp., Interpretation: The first standardised HAI surveillance network in India has succeeded in implementing locally adapted and context-appropriate protocols consistently across hospitals and has been able to identify a large number of HAIs. Network data show high HAI and antimicrobial resistance rates in tertiary hospitals, showing the importance of implementing multimodal HAI prevention and antimicrobial resistance containment strategies., Funding: US Centers for Disease Control and Prevention cooperative agreement with All India Institute of Medical Sciences, New Delhi., Translation: For the Hindi translation of the abstract see Supplementary Materials section., Competing Interests: Declaration of interests We declare no competing interests., (Copyright © 2022 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY-NC-ND 4.0 license. Published by Elsevier Ltd.. All rights reserved.)

Background: Metformin, by reducing intracellular Mycobacterium tuberculosis growth, can be considered an adjunctive therapy to anti-tuberculosis treatment (ATT). We determined whether metformin with standard ATT reduces time to sputum culture conversion and tissue inflammation in adults with pulmonary tuberculosis (PTB)., Methods: In a randomized, 8-week, clinical trial, newly diagnosed, culture-positive PTB patients were randomized to standard ATT (HREZ = control arm) or standard ATT plus daily 1000 mg metformin (MET-HREZ = Metformin with Rifampicin [METRIF] arm) for 8 weeks during 2018-2020 at 5 sites in India. The primary end point was time to sputum culture conversion by liquid culture during 8 weeks of ATT. Plasma inflammatory markers were estimated in a subset. A Cox proportional hazard model was used to estimate time and predictors of culture conversion., Results: Of the 322 patients randomized, 239 (74%) were male, and 212 (66%) had bilateral disease on chest radiograph with 54 (18%) showing cavitation. The median time to sputum culture conversion by liquid culture was 42 days in the METRIF arm and 41 days in the control arm (hazard ratio, 0.8; 95% confidence interval [CI], .624-1.019). After 8 weeks of ATT, cavitary lesions on X-ray (7, 5.3% vs 18, 12.9%; relative risk, 0.42; 95% CI, .18-.96; P = .041) and inflammatory markers were significantly lower in the METRIF arm. Higher body mass index and lower sputum smear grading were associated with faster sputum culture conversion., Conclusions: The addition of metformin to standard ATT did not hasten sputum culture conversion but diminished excess inflammation, thus reducing lung tissue damage as seen by faster clearance on X-ray and reduced inflammatory markers., Clinical Trials Registration: Clinical Trial Registry of India (CTRI/2018/01/011176)., Competing Interests: Potential conflicts of interest. All authors: No reported conflicts of interest. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest., (© The Author(s) 2021. Published by Oxford University Press for the Infectious Diseases Society of America.)

The epidemiology of Mycoplasma pneumoniae (Mp) is poorly understood in India. The present study was conducted to identify the prevalence of Mp in a large set of patients with acute respiratory tract infections (ARI) in an Indian tertiary hospital. During 2015-2020, we tested throat swab specimens from patients with the clinical diagnosis of ARI ( n  = 1,098) by a real-time PCR and compared the demographic, clinical, laboratory, and outcome data of Mp-positive and Mp-negative patients. During the study period, 5% (55/1,098) of the tested samples were positive for Mp by PCR. School-aged children and young adults represented 36% (20/55) of the cases and 47.3% (26/55) of the cases were registered during the summer and monsoon. Among the Mp-positive patients, 61.8% (34/55) had underlying conditions; the most common were malignancy ( n  = 12; 21.8%) and hypertension ( n  = 6; 10.9%). Fever (98.2% versus 84.9%; P  = 0.006), and pharyngitis (27.3% versus 16.3%; P  = 0.034) were significantly common in the Mp-positive group than Mp-negative group. Among the Mp-positive group, 20% (11/55) of patients were admitted to an intensive care unit and a total of 7/55 (12.7%) patients received ventilatory support. The mortality in the Mp-positive cohort was 13.3%. The study provides baseline data regarding Mp prevalence and clinical characteristics. The application of molecular assays for diagnosing this pathogen among hospitalized patients with ARI could reduce inappropriate empirical antibiotic treatment and improve patient outcomes. Further large-scale studies are required to avoid the underdiagnosis of Mp infections in India and such studies should address some research gaps, such as macrolide resistance and molecular typing. IMPORTANCE M. pneumoniae (Mp) is a significant pathogen causing atypical pneumonia but by far these infections are underreported clinical entities in India. In the present study, we report the prevalence of Mp and describe the demographic and baseline clinical data of Mp-positive cases in an Indian tertiary care hospital. Our study may improve the clinician's awareness of this important agent of respiratory infection therefore timely and accurate diagnostic tools can be applied for patient management decisions and outcomes.

Background: The plaque reduction neutralization test (PRNT) is the gold standard to detect the neutralizing capacity of serum antibodies. Neutralizing antibodies confer protection against further infection. The present study measured the antibody level against SARS-CoV-2 among laboratory-confirmed COVID-19 cases and evaluated whether the presence of anti-SARS-CoV-2 antibodies indicates virus neutralizing capacity. Methods: One hundred COVID-19 confirmed cases were recruited. Their sociodemographic details and history of COVID-19 vaccination, contact with positive COVID-19 cases, and symptoms were ascertained using a self-developed semi-structured interview schedule. Serum samples of the participants were collected within three months from the date of the positive report of COVID-19. The presence of anti-SARS-CoV-2 antibodies (IgA, IgG and IgM antibodies), receptor binding domain antibodies (anti-RBD), and neutralizing antibodies were measured. Findings: Almost all the participants had anti-SARS-CoV-2 antibodies (IgA, IgG and IgM) (99%) and anti-RBD IgG antibodies (97%). However, only 69% had neutralizing antibodies against SARS-CoV-2. Anti-RBD antibody levels were significantly higher among participants having neutralizing antibodies compared with those who did not. Interpretation: The present study highlights that the presence of antibodies against SARS-CoV-2, or the presence of anti-RBD antibodies does not necessarily imply the presence of neutralizing antibodies.

Background: Surge of SARS CoV-2 infections ascribed to omicron variant began in December 2021 in New Delhi. We determined the infection and reinfection density in a cohort of health care workers (HCWs) along with vaccine effectiveness (VE) against symptomatic infection within omicron transmission period (considered from December 01, 2021 to February 25, 2022., Methods: This is an observational study from the All India Institute of Medical Sciences, New Delhi. Data were collected telephonically. Person-time at risk was counted from November 30, 2021 till date of infection/ reinfection, or date of interview. Comparison of clinical features and severity was done with previous pandemic periods. VE was estimated using test-negative case-control design [matched pairs (for age and sex)]. Vaccination status was compared and adjusted odds ratios (OR) were computed by conditional logistic regression. VE was estimated as (1-adjusted OR)X100-., Findings: 11474 HCWs participated in this study. The mean age was 36⋅2 (±10⋅7) years. Complete vaccination with two doses were reported by 9522 (83%) HCWs [8394 (88%) Covaxin and 1072 Covishield (11%)]. The incidence density of all infections and reinfection during the omicron transmission period was 34⋅8 [95% Confidence Interval (CI): 33⋅5-36⋅2] and 45⋅6 [95% CI: 42⋅9-48⋅5] per 10000 person days respectively. The infection was milder as compared to previous periods. VE was 52⋅5% (95% CI: 3⋅9-76⋅5, p  = 0⋅036) for those who were tested within 14-60 days of receiving second dose and beyond this period (61-180 days), modest effect was observed., Interpretation: Almost one-fifth of HCWs were infected with SARS CoV-2 during omicron transmission period, with predominant mild spectrum of COVID-19 disease. Waning effects of vaccine protection were noted with increase in time intervals since vaccination., Funding: None., Competing Interests: We declare no competing interests., (© 2022 The Authors.)

Background: Statins and aspirin have been proposed for treatment of COVID-19 because of their anti-inflammatory and anti-thrombotic properties. Several observational studies have shown favourable results. There is a need for a randomised controlled trial., Methods: In this single-center, open-label, randomised controlled trial, 900 RT-PCR positive COVID-19 patients requiring hospitalisation, were randomly assigned to receive either atorvastatin 40 mg (Group A, n = 224), aspirin 75 mg (Group B, n = 225), or both (Group C, n = 225) in addition to standard of care for 10 days or until discharge whichever was earlier or only standard of care (Group D, n = 226). The primary outcome variable was clinical deterioration to WHO Ordinal Scale for Clinical Improvement ≥ 6. The secondary outcome was change in serum C-reactive protein, interleukin-6, and troponin I., Results: The primary outcome occurred in 25 (2.8%) patients: 7 (3.2%) in Group A, 3 (1.4%) in Group B, 8 (3.6%) in Group C, and 7 (3.2%) in Group D. There was no difference in primary outcome across the study groups (P = 0.463). Comparison of all patients who received atorvastatin or aspirin with the control group (Group D) also did not show any benefit [Atorvastatin: HR 1.0 (95% CI 0.41-2.46) P = 0.99; Aspirin: HR 0.7 (95% CI 0.27-1.81) P = 0.46]. The secondary outcomes revealed lower serum interleukin-6 levels among patients in Groups B and C. There was no excess of adverse events., Conclusions: Among patients admitted with mild to moderate COVID-19 infection, additional treatment with aspirin, atorvastatin, or a combination of the two does not prevent clinical deterioration. Trial Registry Number CTRI/2020/07/026791 ( http://ctri.nic.in ; registered on 25/07/2020)., (© 2022. The Author(s).)