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Introduction: Non-small cell lung cancer (NSCLC) is the leading cause of mortality globally. Early imaging detection modalities are associated with high false-positive rates and radiation exposure. A non-invasive biomarker can serve as an improvised method for early detection. MicroRNAs can serve as a potential non-invasive biomarker as they are stable in circulation, tissue or biological process-specific, easy to detect, cost-effective, and not associated with radiation hazards. This study validates circulating microRNA in NSCLC of the Indian population and studies its correlation with clinicopathological parameters., Materials and Methods: Circulating microRNA (-miR-193b, miR-301a, miR-7, and miR-25) was evaluated in 101 cases of tissue-proven NSCLC and 28 controls in serum samples., Results: There were 67 male and 34 female patients (Male: Female = 1.97:1). The age range was 25 to 86 years with a median age of 60 years. There was a significant upregulation in the expression of miR-193b in the NSCLC group as compared to controls ( P = 0.034). MiR-7 was also upregulated while miR-25 and miR-301a were downregulated in NSCLC as compared to controls; however, a level of significance was not achieved. ROC curve analysis for miR-193b showed an AUC of 0.636 (95% CI, 0.522-0.750; P- value = 0.036) between NSCLC cases and controls., Conclusion: The present study showed variable expression of the above-studied miRNAs. MiR-193b showed a significant upregulation in cancer patients; however, the other three miRNAs were not conclusive. This suggests that profiling of microRNA in each population is essential to search for a valid non-invasive biomarker in that population., (Copyright © 2023 Copyright: © 2023 Indian Journal of Pathology and Microbiology.)

Study Objectives: Studies have indicated that sleep abnormalities are a strong risk factor for developing cognitive impairment, cardiomyopathies, and neurodegenerative disorders. However, neuroimaging modalities are unable to show any consistent markers in obstructive sleep apnea (OSA) patients. We hypothesized that, compared with those of the control cohort, advanced diffusion MRI metrics could show subtle microstructural alterations in the brains of patients with OSA., Methods: Sixteen newly diagnosed patients with moderate to severe OSA and 15 healthy volunteers of the same age and sex were considered healthy controls. Multishell diffusion MRI data of the brain, along with anatomical data (T1 and T2 images), were obtained on a 3T MRI system (Siemens, Germany) after a polysomnography (PSG) test for sleep abnormalities and a behavioral test battery to evaluate cognitive and executive brain functions. Diffusion MRI data were used to compute diffusion tensor imaging and diffusion kurtosis imaging (DKI) parameters along with white-matter tract integrity (WMTI) metrics for only parallel white-matter fibers., Results: OSA was diagnosed when the patient's apnea-hypopnea index was ≥ 15. No significant changes in cognitive or executive functions were observed in the OSA cohort. DKI parameters can show significant microstructural alterations in the white-matter region, while the WMTI metric, the axonal-water-fraction (fp), reveals a significant decrease in OSA patients concerning the control cohort., Conclusions: Advanced diffusion MRI-based microstructural alterations in the white-matter region of the brain suggest that white-matter tracts are more sensitive to OSA-induced intermittent hypoxia., (© The Author(s) 2024. Published by Oxford University Press on behalf of Sleep Research Society.)

Background: The International Society for Human and Animal Mycology (ISHAM) working group proposed recommendations for managing allergic bronchopulmonary aspergillosis (ABPA) a decade ago. There is a need to update these recommendations due to advances in diagnostics and therapeutics., Methods: An international expert group was convened to develop guidelines for managing ABPA (caused by Aspergillus spp.) and allergic bronchopulmonary mycosis (ABPM; caused by fungi other than Aspergillus spp.) in adults and children using a modified Delphi method (two online rounds and one in-person meeting). We defined consensus as ≥70% agreement or disagreement. The terms "recommend" and "suggest" are used when the consensus was ≥70% and <70%, respectively., Results: We recommend screening for A. fumigatus sensitisation using fungus-specific IgE in all newly diagnosed asthmatic adults at tertiary care but only difficult-to-treat asthmatic children. We recommend diagnosing ABPA in those with predisposing conditions or compatible clinico-radiological presentation, with a mandatory demonstration of fungal sensitisation and serum total IgE ≥500 IU·mL -1 and two of the following: fungal-specific IgG, peripheral blood eosinophilia or suggestive imaging. ABPM is considered in those with an ABPA-like presentation but normal A. fumigatus -IgE. Additionally, diagnosing ABPM requires repeated growth of the causative fungus from sputum. We do not routinely recommend treating asymptomatic ABPA patients. We recommend oral prednisolone or itraconazole monotherapy for treating acute ABPA (newly diagnosed or exacerbation), with prednisolone and itraconazole combination only for treating recurrent ABPA exacerbations. We have devised an objective multidimensional criterion to assess treatment response., Conclusion: We have framed consensus guidelines for diagnosing, classifying and treating ABPA/M for patient care and research., Competing Interests: Conflict of interest: R. Agarwal has received grants from Cipla Pharmaceuticals, India for conducting research in ABPA. D.W. Denning and family hold founder shares in F2G Ltd, a University of Manchester spin-out antifungal discovery company, and share options in TFF Pharma. He acts or has recently acted as a consultant to Pulmatrix, Pulmocide, Biosergen, TFF Pharmaceuticals, Rostra Therapeutics, Mucpharma PTY and Lifemine Therapeutics. In the last 3 years, he has been paid for talks on behalf of Mundipharma, Bio-Rad, Basilea, Gilead, Avir and Pfizer. He has been involved in multiple guideline groups, primarily focused on diagnostics and aspergillosis. D. Armstrong-James holds share options in Pulmocide Ltd. K. Asano is partially supported by a research grant on allergic disease and immunology from the Japan Agency for Medical Research and Development under grant number 22ek0410097. S.H. Chotirmall has served on advisory boards for CSL Behring, Pneumagen Ltd and Boehringer Ingelheim, on data monitoring boards for Inovio Pharmaceuticals and Imam Abdulrahman Bin Faisal University, and has received personal fees from AstraZeneca and Chiesi Farmaceutici, all unrelated to this work. H.J.F. Salzer has received honoraria for lectures or consulting fees from Ismed, GlaxoSmithKline, AstraZeneca, Advanz Pharma, MSD and Chiesi, all unrelated to this work. J.D. Chalmers has received research grants from AstraZeneca, Boehringer Ingelheim, GlaxoSmithKline, Gilead Sciences, Grifols, Novartis, Insmed and Trudell, and received consultancy or speaker fees from Antabio, AstraZeneca, Boehringer Ingelheim, Chiesi, GlaxoSmithKline, Insmed, Janssen, Novartis, Pfizer, Trudell and Zambon. C. Godet has received speaker fees and travel support from Pfizer and MSD, fees for board memberships from SOS Oxygène and Pulmatrix, and grant support from Ohre Pharma, Pfizer, MSD, SOS Oxygène, ISIS Medical, LVL Médical, Oxyvie, Vivisol, Elivie, CF Santé, Boehringer, Sandoz and AstraZeneca. M. Joest has received honoraria for lectures or grants from ALK-Abelló, AstraZeneca, Bencard, Berlin-Chemie, Boehringer Ingelheim, GlaxoSmithKline and HAL Allergy, all unrelated to this work. P. Nair reports grants and personal fees from AstraZeneca, Teva and Sanofi, personal fees from Equillium, Arrowhead Pharma and GlaxoSmithKline, and grants from Foresee and Cyclomedica, outside the submitted work. C.G. Baxter serves on strategic advisory board for Nob Hill Therapeutics Ltd. W.J. Calhoun is a member of the scientific advisory board of Pulmatrix, and that work is unrelated to this publication. O.A. Cornely reports grants from Cidara, F2G, Gilead, MSD, Mundipharma, Pfizer and Scynexis, consulting fees from AiCuris, Basilea, Cidara, Gilead, IQVIA, Matinas, Pfizer, PSI, Pulmocide and Scynexis, honoraria for lectures from Al-Jazeera, Gilead, Knight, MSD, Pfizer and Shionogi, and payment for expert testimony from Cidara. J.A. Douglass has received honoraria for educational presentations from AstraZeneca, GlaxoSmithKline, Novartis and CSL, has served on advisory boards for Sanofi-Aventis, Novartis, GlaxoSmithKline, AstraZeneca, Immunosis and CSL, and has undertaken contracted or investigator-initiated research on behalf of GlaxoSmithKline, Novartis, Immunosis, AstraZeneca, Sanofi-Aventis, Grifols, CSL, BioCryst and Equillium. R. Moss reports consulting fees from the Cystic Fibrosis Foundation, Astellas Pharma Inc., Nob Hill Therapeutics Inc., Pulmatrix, Mayne Pharma, Zambon Company SpA, Aridis Pharmaceuticals Inc., Regeneron Pharmaceuticals Inc. and 4D Molecular Therapeutics, royalties from UpToDate, Inc., and is a member of the board of directors for the Cystic Fibrosis Research Institute. D. Seidel received speaker fees from Pfizer, outside of the submitted work. R. Sprute has received speaker fees from Hikma and Pfizer, and travel support from Pfizer, all outside of the submitted work. The remaining authors have no potential conflicts of interest to disclose., (Copyright ©The authors 2024.)

Abstract: A 15-year-old boy presented with a sudden onset of breathlessness for 7 days, gradual loss of weight of 17.6 lbs over the last month and progressive hoarseness of voice for 7 months. The contrast-enhanced computed tomography (CECT) scan revealed a heterogeneously enhancing lesion in the anterior mediastinum with multiple discrete lymph nodes in the cervical and mediastinal locations. The GeneXpert MTB/RIF assay performed on the CT-guided biopsy of the mass was negative, but the culture for Mycobacterium tuberculosis was positive at 7 weeks of incubation. There was a suboptimal radiological response after 6 months of treatment. First-line drug susceptibility testing (DST) performed by line probe assay (LPA) on the positive culture detected high-level resistance to isoniazid. The treatment was modified as per DST results to which the patient responded well., (Copyright © 2024 Copyright: © 2024 Indian Chest Society.)

The persistent morbidity and mortality associated with tuberculosis (TB), despite our continued efforts, has been long recognized, and the rise in the incidence of drug-resistant TB adds to the preexisting concern. The bulk of the TB burden is confined to low-income countries, and rigorous efforts are made to detect, notify, and systematically treat TB. Efforts have been infused with renewed vigor and determination by the World Health Organization (WHO) to eliminate tuberculosis in the near future. Different health agencies worldwide are harvesting all possible strategies apart from consolidating ongoing practices, including prevention of the development of active disease by treating latent TB infection (LTBI). The guidelines for the same were already provided by the WHO and were then adapted in the Indian guidelines for the treatment of LTBI in 2021. While the long-term impact of TBI treatment is awaited, in this article, we aim to discuss the implications in the Indian context., (Copyright © 2024 Copyright: © 2024 Indian Chest Society.)

Background: Pulmonary sarcoidosis (SAR) and tuberculosis (TB) are two granulomatous lung-diseases and often pose a diagnostic challenge to a treating physicians., Objective: The present study aims to explore the diagnostic potential of NMR based serum metabolomics approach to differentiate SAR from TB., Materials and Method: The blood samples were obtained from three study groups: SAR (N = 35), TB (N = 28) and healthy normal subjects (NC, N = 56) and their serum metabolic profiles were measured using 1D 1 H CPMG (Carr-Purcell-Meiboom-Gill) NMR spectra recorded at 800 MHz NMR spectrometer. The quantitative metabolic profiles were compared employing a combination of univariate and multivariate statistical analysis methods and evaluated for their diagnostic potential using receiver operating characteristic (ROC) curve analysis., Results: Compared to SAR, the sera of TB patients were characterized by (a) elevated levels of lactate, acetate, 3-hydroxybutyrate (3HB), glutamate and succinate (b) decreased levels of glucose, citrate, pyruvate, glutamine, and several lipid and membrane metabolites (such as very-low/low density lipoproteins (VLDL/LDL), polyunsaturated fatty acids, etc.)., Conclusion: The metabolic disturbances not only found to be well in concordance with various previous reports, these further demonstrated very high sensitivity and specificity to distinguish SAR from TB patients suggesting serum metabolomics analysis can serve as surrogate method in the diagnosis and clinical management of SAR., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

COVID-19-associated pulmonary aspergillosis (CAPA) remains a high mortality mycotic infection throughout the pandemic, and glucocorticoids (GC) may be its root cause. Our aim was to evaluate the effect of systemic GC treatment on the development of CAPA. We systematically searched the PubMed, Google Scholar, Scopus and Embase databases to collect eligible studies published until 31 December 2022. The pooled outcome of CAPA development was calculated as the log odds ratio (LOR) with 95% confidence intervals (CI) using a random effect model. A total of 21 studies with 5174 patients were included. Of these, 20 studies with 4675 patients consisting of 2565 treated with GC but without other immunomodulators (GC group) and 2110 treated without GC or other immunomodulators (controls) were analysed. The pooled LOR of CAPA development was higher for the GC group than for the controls (0.54; 95% CI: 0.22, 0.86; p < .01). In the subgroups, the pooled LOR was higher for high-dose GC (0.90; 95% CI: 0.17, 1.62: p = .01) and dexamethasone (0.71; 95% CI: 0.35, 1.07; p < .01) but had no significant difference for low-dose GC (0.41; 95% CI: -0.07, 0.89; p = .09), and non-dexamethasone GC (0.21; 95% CI: -0.36, 0.79; p = .47), treated patients versus controls. GC treatment increases the risk of CAPA development, and this risk is particularly associated with the use of high-dose GC or dexamethasone treatment., (© 2023 Wiley-VCH GmbH. Published by John Wiley & Sons Ltd.)

Background: Computed tomography (CT)-guided biopsy is emerging as a preferred and safe method for obtaining tissue samples in pleural diseases., Objective: This study aimed to evaluate the diagnostic yield and safety of percutaneous CT-guided biopsy in pleural diseases and to find CT findings predictive of malignant neoplastic pleural disease., Material and Methods: This retrospective study included 77 patients with pleural disease who underwent CT-guided pleural biopsies from July 2013 to May 2020. All procedures were performed with a coaxial semi-automatic biopsy device. Histopathology was performed in all cases, and additional tests such as immunohistochemistry (IHC) or microbiological analysis were carried out depending on clinical suspicion. The correlation of CT findings with final diagnosis was performed by Chi-square, Fisher's exact test and logistic regression analysis., Results: The overall technical success rate of CT-guided pleural biopsy was 100% with a diagnostic yield of 96.1%. No major complication was encountered, with minor complications encountered in the form of minimal pneumothorax and chest pain. Malignant pleural conditions constituted the largest group including metastatic adenocarcinoma as the most common (31.2%), followed by metastatic squamous cell carcinoma and mesothelioma. Tubercular pleural involvement was the second most common category (16.9%). The cartridge-based nucleic acid amplification test (CB-NAAT) assay had 90% sensitivity on pleural tissue in tubercular cases. CT features predictive of malignancy were irregular and nodular pleural thickening, mediastinal and diaphragmatic pleural involvement and mediastinal/chest wall invasion. There was a good correlation between higher pleural thicknesses with malignant outcome., Conclusion: Percutaneous CT-guided biopsy is a safe method for obtaining pleural tissue samples with high diagnostic yield. CT findings provide clues, which favour malignant pleural involvement.

Background: Association between the ABO blood group and patient outcomes in COVID-19 patients is still unexplored. A known association may help to understand possible risks in advance to the management of such COVID-19 patients. The present study was designed to test such association if there is any, between the ABO blood group and the severity of COVID-19 patients., Methods: The present hospital-based observational study was conducted at a COVID-19 dedicated tertiary care hospital in North India over a period of six months during the first wave of the pandemic in the country. Five hundred consecutive patients, who tested positive for COVID-19 using RT-PCR on oropharyngeal/nasopharyngeal swabs, admitted to the hospital were included in the study. ABO and Rhesus (Rh) blood grouping was done on leftover hematology blood samples using gel column agglutination technology. Required clinical details of patients including age, gender, clinical symptoms, comorbidities, outcomes, etc., were obtained from the patient's case sheets., Results: The most common blood group was 'B' (42.8%) followed by 'O' (23.4%), and 'A' (22.4%) while the least common was 'AB' (11.4%). Rh positive was seen in 96.2% while 3.8% were negative. Baseline characteristics were comparable including length of hospital stay, duration of symptoms, and associated comorbid illnesses. The need for intensive care unit (ICU) admissions ( P = 0.05) and intubations ( P = 0.20) was similar across all four blood groups. Differences in the severity of COVID-19 disease and mortalities among the groups were non-significant., Conclusion: There was no observed association found between the ABO blood group and COVID-19 infection requiring hospitalization, ICU admission, intubation, and outcomes. However, there was a higher proportion of breathlessness and the presence of at least one comorbidity in blood group O as compared to others., Competing Interests: There are no conflicts of interest., (Copyright: © 2023 Journal of Family Medicine and Primary Care.)

Objectives: Testing for EGFR, ALK, ROS1 and MET alterations in paired tissue and plasma samples of treatment-naïve patients of NSCLC and correlating their status with overall survival., Materials and Methods: One hundred treatment-naïve patients were recruited after obtaining informed consent. Ten ml of blood was collected within a period of two weeks from histological diagnosis, prior to the start of any treatment. DNA & RNA extraction was done from formalin-fixed paraffin embedded (FFPE) tissue and total cell-free nucleic acid extraction was done from plasma samples. EGFR mutation, ALK, ROS1 and MET rearrangements were tested by ARMS (Amplification Refractory Mutation System) PCR. All statistical analyses were conducted in R version 4.1.1., Results: A total of 61 cases showed molecular alterations in tissue samples which included EGFR mutations (47), ALK rearrangements (12), ROS1 fusion (2). MET alteration was not detected. Forty-three cases showed EGFR mutations in plasma, 26 of which were concurrently positive in tissue. Concordance observed was 62%. ALK-EML4 rearrangement, ROS1 fusion and MET were not detected in plasma samples. Sensitivity and specificity for detection of EGFR mutation in plasma were 55.3% and 67.9% respectively. Univariate Cox regression analysis showed a positive association between EGFR mutation in tissue and overall survival (HR = 0.4; 95% CI: 0.2-0.7; p = 0.003) and improved overall survival in those who received targeted therapy (HR = 0.29; 95% CI: 0.1-0.8; p = 0.02)., Conclusion: Concurrent testing in tissue and liquid biopsy in NSCLC increased the detection of EGFR mutations (47% to 64%). This has substantial implications in deciding treatment and administration targeted therapy and the consequent overall survival.

A 42-year-old male presented with a dry cough, breathlessness, and fever. He underwent a computed tomography that revealed large consolidation in the right lung. Biopsy revealed Cryptococcus neoformans . He was on antifungal for 4 months with no clinicoradiological improvement. 18 F- fluorodeoxyglucose positron emission tomography/computed tomography ( 18 F-FDG PET/CT) showed consolidations in the right lung with multiple lung nodules. 18 F-FDG PET/CT ascertains the diagnosis of residual fungal infection and rules out extrapulmonary involvement., Competing Interests: There are no conflicts of interest., (Copyright: © 2023 Indian Journal of Nuclear Medicine.)

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.

Background and Aim: Diffuse alveolar hemorrhage (DAH) is a life-threatening condition due to the extravasation of blood in the alveoli, resulting in hypoxemia and even acute respiratory distress syndrome. This study aimed to describe the clinico-radio-pathological profile of patients diagnosed with DAH and classify it into immune and nonimmune DAH., Methods: This was a retrospective analytical study. Of a total of 1000 cases of bronchoalveolar lavage fluids (BALF) received for cytological examination, patients fulfilling the clinical, radiological, and laboratory details of cases satisfying the clinical and cytological criteria of DAH (n=47) were studied., Results: The most common cause of immune DAH was ANCA-associated vasculitis (n=13, 27.6%), and that of nonimmune DAH was infections (n=10, 21.3%). Twenty-nine patients (61.7%) had hemoptysis. The most common radiological finding was ground-glass opacities (n=33, 70.2%). In univariate analysis, female sex, mean hemoglobin at admission, total leucocyte count (TLC), platelet count, and erythrocyte sedimentation rate (ESR) were significantly associated with immune-DAH. However, in multivariate analysis, female sex, higher TLC, high platelets, and high ESR were significantly associated with immune DAH. Patients were treated with corticosteroids (n=25, 46.3%), intravenous cyclophosphamide (n=12, 22.2%), plasma exchange (n=7, 13.0%), intravenous immunoglobulin (n=5, 9.3%) and rituximab (n=5, 9.3%). The overall mortality was 8.5% (n=4)., Conclusions: DAH is a life-threatening syndrome that may be classified into immune and nonimmune DAH. Immune-DAH requires aggressive management, whereas nonimmune DAH cases respond best to conservative management.

Introduction: There is a dearth of biomarkers in Idiopathic Inflammatory Myopathies (IIM) to recognize ongoing muscle inflammation and distinguish damage from activity. Since IIM is an autoantibody-mediated disease with tertiary lymphoid organogenesis reported in the diseased muscles, we aimed to study the peripheral blood T helper (Th) subset profiling as a plausible reflection of ongoing muscle inflammation., Methods: Fifty-six patients of IIM were compared with 21 healthy controls (HC) and 18 patients with sarcoidosis. Th1, Th17, Th17.1, and Treg cells were identified after stimulation assays (BD Biosciences). Myositis autoantibodies were tested by line immunoassay (Euroimmune, Germany)., Results: All Th subsets were elevated in IIM as compared with HC. As compared to HC, PM had elevated Th1 and Treg while Th17 and Th17.1 populations were higher in OM. Patients with sarcoidosis had higher Th1 and Treg but lower Th17 population as compared to IIM {Th1(69.1% vs 49.65%, p<0.0001), {Treg (12.05% vs 6.2%, p<0.0001), {Th17 (2.49% vs 4.4%, p<0.0001)}. Similar results were obtained when sarcoidosis ILD was compared with IIM ILD with a higher Th1 and Treg population but lower Th17 population in the former. No difference in T cell profile was observed after stratification for MSA positivity, type of MSA, clinical features of IIM and disease activity., Conclusion: Th subsets in IIM are distinct from sarcoidosis and HC with a TH17 predominant paradigm, creating a case of exploring Th17 pathway and IL-17 blockers for the treatment of IIM. However, cell profiling cannot distinguish active from inactive disease limiting its predictive potential as a biomarker of activity in IIM., (Copyright © 2022 Elsevier España, S.L.U. and Sociedad Española de Reumatología y Colegio Mexicano de Reumatología. All rights reserved.)

Introduction: Universal coverage of vaccines alone cannot be relied upon to protect at-risk populations in lower- and middle-income countries against the impact of the coronavirus disease 2019 (COVID-19) pandemic and newer variants. Live vaccines, including Bacillus Calmette-Guérin (BCG), are being studied for their effectiveness in reducing the incidence and severity of COVID-19 infection., Methods: In this multi-centre quadruple-blind, parallel assignment randomised control trial, 495 high-risk group adults (aged 18-60 years) were randomised into BCG and placebo arms and followed up for 9 months from the date of vaccination. The primary outcome was the difference in the incidence of COVID-19 infection at the end of 9 months. Secondary outcomes included the difference in the incidence of severe COVID-19 infections, hospitalisation rates, intensive care unit stay, oxygen requirement and mortality at the end of 9 months. The primary analysis was done on an intention-to-treat basis, while safety analysis was done per protocol., Results: There was no significant difference in the incidence rates of cartridge-based nucleic acid amplification test (CB-NAAT) positive COVID-19 infection [odds ratio (OR) 1.08, 95% confidence interval (CI) 0.54-2.14] in the two groups, but the BCG arm showed a statistically significant decrease in clinically diagnosed (symptomatic) probable COVID-19 infections (OR 0.38, 95% CI 0.20-0.72). Compared with the BCG arm, significantly more patients developed severe COVID-19 pneumonia (CB-NAAT positive) and required hospitalisation and oxygen in the placebo arm (six versus none; p = 0.03). One patient belonging to the placebo arm required intensive care unit (ICU) stay and died. BCG had a protective efficacy of 62% (95% CI 28-80%) for likely symptomatic COVID-19 infection., Conclusions: BCG is protective in reducing the incidence of acute respiratory illness (probable symptomatic COVID-19 infection) and severity of the disease, including hospitalisation, in patients belonging to the high-risk group of COVID-19 infection, and the antibody response persists for quite a long time. A multi-centre study with a larger sample size will help to confirm the findings in this study., Clinical Trials Registry: Clinical Trials Registry India (CTRI/2020/07/026668)., (© 2022. The Author(s).)

Introduction: Lower respiratory tract infections (LRTIs) among renal transplant recipients (RTRs) are a significant cause of morbidity and mortality. This study aimed to analyse the aetiology, outcome, and risk factors associated with mortality., Methods: We analysed baseline transplant characteristics, symptoms, hospital course, laboratory, serological and microbial results, and their association with the outcome of all RTRs between January 2011 and December 2019., Results: A total of 206 LRTI patients out of 1051 RTRs were analysed. The incidence proportion was nearly 22 episodes per 1000 patients per year. The mean age was 39.3 years, with male predominance. Bacterial was the most common aetiology (53%), and staphylococcus was the most common species. Among the fungal causes (14%), 68% had aspergillus infection. More than one-third RTRs died during the hospital course mainly because of bacterial causes (42.6%). The aspergillus infection was the most common fungus associated with 50% mortality. On multi-variate analysis, sepsis, septic shock, and the need for mechanical ventilation independently predicted mortality., Conclusion: Bacterial aetiology was the most common cause; though the fungal aetiology was seen less, it was associated with higher mortality. Mortality in RTR with LRTI was associated with sepsis, septic shock, and the need for mechanical ventilation., Competing Interests: None

Background: COVID-19-associated pulmonary aspergillosis (CAPA) has been widely reported but homogenous large cohort studies are needed to gain real-world insights about the disease., Methods: We collected clinical and laboratory data of 1161 patients hospitalised at our Institute from March 2020 to August 2021, defined their CAPA pathology, and analysed the data of CAPA/non-CAPA and deceased/survived CAPA patients using univariable and multivariable models., Results: The overall prevalence and mortality of CAPA in our homogenous cohort of 1161 patients were 6.4% and 47.3%, respectively. The mortality of CAPA was higher than that of non-CAPA patients (hazard ratio: 1.8 [95% confidence interval: 1.1-2.8]). Diabetes (odds ratio [OR] 1.92 [1.15-3.21]); persistent fever (2.54 [1.17-5.53]); hemoptysis (7.91 [4.45-14.06]); and lung lesions of cavitation (8.78 [2.27-34.03]), consolidation (9.06 [2.03-40.39]), and nodules (8.26 [2.39-28.58]) were associated with development of CAPA by multivariable analysis. Acute respiratory distress syndrome (ARDS) (2.68 [1.09-6.55]), a high computed tomography score index (OR 1.18 [1.08-1.29]; p < .001), and pulse glucocorticoid treatment (HR 4.0 [1.3-9.2]) were associated with mortality of the disease. Whereas neutrophilic leukocytosis (development: 1.09 [1.03-1.15] and mortality: 1.17 [1.08-1.28]) and lymphopenia (development: 0.68 [0.51-0.91] and mortality: 0.40 [0.20-0.83]) were associated with the development as well as mortality of CAPA., Conclusion: We observed a low but likely underestimated prevalence of CAPA in our study. CAPA is a disease with high mortality and diabetes is a significant factor for its development while ARDS and pulse glucocorticoid treatment are significant factors for its mortality. Cellular immune dysregulation may have a central role in CAPA from its development to mortality., (© 2022 Wiley-VCH GmbH.)

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.)

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.

Coronavirus disease-2019 (COVID-19)-associated pulmonary aspergillosis (CAPA) is a new disease characterized by secondary Aspergillus mold infection in patients with COVID-19. It primarily affects patients with COVID-19 in critical state with acute respiratory distress syndrome, requiring intensive care and mechanical ventilation. CAPA has a higher mortality rate than COVID-19, posing a serious threat to affected individuals. COVID-19 is a potential risk factor for CAPA and has already claimed a massive death toll worldwide since its outbreak in December 2019. Its second wave is currently progressing towards a peak, while the third wave of this devastating pandemic is expected to follow. Therefore, an early and accurate diagnosis of CAPA is of utmost importance for effective clinical management of this highly fatal disease. However, there are no uniform criteria for diagnosing CAPA in an intensive care setting. Therefore, based on a review of existing information and our own experience, we have proposed new criteria in the form of practice guidelines for diagnosing CAPA, focusing on the points relevant for intensivists and pulmonary and critical care physicians. The main highlights of these guidelines include the role of CAPA-appropriate test specimens, clinical risk factors, computed tomography of the thorax, and non-culture-based indirect and direct mycological evidence for diagnosing CAPA in the intensive care unit. These guidelines classify the diagnosis of CAPA into suspected, possible, and probable categories to facilitate clinical decision-making. We hope that these practice guidelines will adequately address the diagnostic challenges of CAPA, providing an easy-to-use and practical algorithm to clinicians for rapid diagnosis and clinical management of the disease.

Background: Our understanding of the pathophysiology of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is still evolving and is limited for prognostication. The study was performed to predict severity and mortality based on hematology parameters in coronavirus disease (COVID-19)., Material and Methods: The study was a single-center retrospective analysis of 240 patients with COVID-19. The hematological parameters were compared between different grades of severity. The receiver operating characteristics (ROC) curve along with the Classification and Regression Trees (CART) methods were used for the analysis., Result: The total leukocyte count, absolute neutrophil count, neutrophil-lymphocyte ratio (NLR), and neutrophil-monocyte ratio (NMR) were increasing along with an increase in severity; while the absolute lymphocyte count and lymphocyte-monocyte ratio (LMR) were decreasing ( P < 0.001). For prediction of severity and mortality on admission, the NLR, NMR, and LMR were significant ( P < 0.001). The NLR, NMR, and LMR had an area under the receiver operating characteristics curve (AUROC) of 0.86 (95% CI of 0.80-0.91), 0.822 (95% CI of 0.76-0.88), and 0.69 (95% CI of 0.60-0.79), respectively, for severity. While the NLR, NMR, and LMR had an AUROC value of 0.85 (95% CI of 0.79-0.92), 0.83 (95% CI of 0.77-0.89), and 0.67 (95% CI of 0.57-0.78), respectively, for mortality., Conclusion: With the increase in severity there was an increase in the total leukocyte count and absolute neutrophil count while the absolute lymphocyte count decreased. On admission, the cut-off value of NLR >5.2, NMR >12.1, while LMR <2.4 may predict severity and mortality in COVID-19., Competing Interests: There are no conflicts of interest., (Copyright: © 2022 Journal of Family Medicine and Primary Care.)

Involvement of the gastrointestinal (GI) system in corona virus disease-19 (COVID-19) in form of diarrhea, loss of taste, nausea, and anorexia is common and associated with poor prognosis. COVID-19 is also associated with a hypercoagulable state that mainly involves the pulmonary vasculature. However, GI complications involving thrombosis are observed infrequently. We report two COVID-19 patients who had two different causes of acute abdomen. The first patient was a 49-year-old male diagnosed with an aortic thrombus along with a splenic infarct. He was diagnosed early and successfully managed with anticoagulants. The second patient was a 30-year-old male who developed pain in the abdomen and was found to have features suggestive of peritonitis. A contrast-enhanced computerized tomography (CECT) scan of the abdomen revealed dilated bowel loops. Immediate exploratory laparotomy was performed; he was found to have jejunal perforation with gangrene. Histopathological examination of the resected specimen showed inflammatory cells with edema and thrombotic vessels. However, he succumbed to sepsis and multiorgan failure. Therefore, it is important to investigate cases of acute abdomen in COVID-19 thoroughly and whenever indicated CT angiogram should be obtained., (© 2022. Indian Society of Gastroenterology.)

Background: Most of the reported risk score models for coronavirus disease 2019 (COVID-19) mortality are based on the levels of inflammatory markers, comorbidities or various treatment modalities, and there is a paucity of risk score models based on clinical symptoms and comorbidities., Methods: To address this need, age, clinical symptoms and comorbidities were used to develop a COVID-19 scoring system (CSS) for early prediction of mortality in severe COVID-19 patients. The CSS was developed with scores ranging from 0 to 9. A higher score indicates higher risk with good discrimination quality presented by Mann Whitney U test and area under receiver operating characteristic curve (AUROC)., Results: Patient age of ≥60 y, cough, breathlessness, diabetes and any other comorbidity (with or without diabetes) are significant and independent risk factors for non-survival among COVID-19 patients. The CSS showed good sensitivity and specificity (i.e. 74.1% and 78.5% at CSS≥5, respectively), with an overall diagnostic accuracy of 82.8%, which was close to the diagnostic accuracy detected in the validation cohort (81.9%). In the validation cohort, high (8-9), medium (5-7) and low (0-4) CSS groups had 54.80%, 28.60% and 6.5% observed mortality, respectively, which was very close to the predicted mortality (62.40%, 27.60% and 5.2%, respectively, by scoring cohort)., Conclusions: The CSS shows a positive relationship between a higher score and proportion of mortality and, as its validation showed, it is useful for the prediction of risk of mortality in COVID-19 patients at an early stage, so that referral for triage and admission can be predetermined even before admission to hospital., (© The Author(s) 2021. Published by Oxford University Press on behalf of Royal Society of Tropical Medicine and Hygiene.)

Severe hypoxia due to coronavirus disease 2019 (COVID-19) is challenging in the intensive care unit (ICU). It is often unresponsive to mechanical ventilation at high positive end-expiratory pressure and the fraction of inspired oxygen combination. The cause of such worsening hypoxia may be microvascular thrombosis in the pulmonary vascular system because of the procoagulant nature of COVID-19 infection. Confirming the diagnosis with computed tomographic pulmonary angiography is not always possible, as the patients are too sick to be shifted. Tissue plasminogen activator (tPA) is recommended for pulmonary thromboembolism with hypotension and worsening hypoxia, as confirmed by computed tomography pulmonary angiography. However, its role in worsening hypoxia because of presumed microthrombi in the pulmonary vasculature in COVID-19 is unclear. We present six cases from our ICU where we used low-dose tPA in COVID-19 refractory hypoxia with presumed microthrombi in the pulmonary vasculature (oligemic lung field, refractory hypoxia, increased D dimer, electrocardiographic features of pulmonary embolism, and right ventricular strain on echocardiography). Oxygenation improved within 6 h and was maintained for up to 48 h in all patients. Therefore, there is a possible role of microthrombi in the mechanism of hypoxia in this setting. An early decision to start low-dose tPA may improve the outcome. However, all patients finally succumbed to sepsis and multiorgan failure later in their course. A systematic review of the literature has also been performed on the mechanism of thrombosis and the use of tPA in hypoxia due to COVID-19., Competing Interests: None

Background & Objectives: The association between hyperglycaemia at admission, diabetes mellitus (DM) status and mortality in hospitalized SARS-CoV-2 infected patients is not clear. The purpose of this study was to determine the relationship between DM, at-admission hyperglycaemia and 28 day mortality in patients admitted with moderate-severe SARS-CoV-2 infection requiring intensive care., Methods: All consecutive moderate-to-severe patients with SARS-CoV-2 infection admitted to the intensive care units (ICUs) over six months were enrolled in this single-centre, retrospective study. The predicators for 28 day mortality were analysed from the independent variables including DM status and hyperglycaemia at-admission., Results: Four hundred and fifty two patients with SARS-CoV-2 were admitted to the ICU, with a mean age of 58.5±13.4 yr, 78.5 per cent being male, HbA 1c of 7.2 per cent (6.3-8.8) and 63.7 per cent having DM. Overall, 28 day mortality was 48.9 per cent. In univariate analysis, mortality in diabetes patients was comparable with non-diabetes (47.9 vs. 50.6%, P=0.58), while it was significantly higher in hyperglycaemic group (60.4 vs. 35.8%, P<0.001). In multivariate Cox regression analysis, after adjusting for age, sex and comorbidities, hyperglycaemia at-admission was an independent risk factor of mortality [hazard ratio (HR) 1.45, 95% confidence interval (CI) (1.06-1.99), P<0.05]., Interpretation & Conclusions: This study showed that the presence of hyperglycaemia at-admission in critically ill SARS-CoV-2 patients was an independent predictor of 28 day mortality. However, the findings may be susceptible to unmeasured confounding, and more research from prospective studies is required.

Purpose: We evaluated T helper lymphocyte profile, including novel Th17 subsets Th17.1 (secrete IFN-γ, associate with corticosteroid resistance) and PD1+Th17 (secrete TGF-β1, implicated in fibrosis), and related cytokines in peripheral blood of Takayasu arteritis (TAK)., Materials and Methods: We evaluated circulating Th1, Th2, Th17, Th17.1, PD1+CD4+ T lymphocytes, PD1+Th17, and Treg lymphocytes, inflammatory (IFN-γ, IL-4, IL-6, IL-17A, IL-23, IL-1β, TNF-α) and regulatory (IL-10, TGF-β1) cytokines in peripheral blood of TAK (n = 57; median age 35 (interquartile range 26-45) years; 40 females) in a cross-sectional design. We studied inflammatory and regulatory cytokines in culture supernatant of peripheral blood mononuclear cells (PBMCs) from TAK following stimulation with anti-CD3/anti-CD28 and their modulation by tacrolimus (immunosuppressive) with/without tadalafil (anti-fibrotic). Furthermore, we followed up immunosuppressive-naïve active TAK (n = 16) and compared T helper lymphocyte populations and cytokines before and after immunosuppressive therapy. Healthy controls (HC, n = 21) and sarcoidosis (disease control, n = 11) were compared against TAK., Results: TAK had higher Th17, Th17.1 and PD1+Th17 lymphocytes than HC (p < 0.001), and higher PD1+CD4+ T lymphocytes than sarcoidosis (p < 0.001). Th17 lymphocytes associated with active TAK after multivariable-adjusted logistic regression (p = 0.008). TAK had greater cytokine secretion from PBMCs (IFN-γ, IL-17A, IL-10 versus HC; IL-6, TNF-α, IL-1β versus HC or sarcoidosis) (p < 0.05). In-vitro, PBMCs from TAK showed reduced secretion of all inflammatory cytokines with tacrolimus, with synergistic reduction in IL-17A, IL-6, IL-1β and IL-10 following addition of tadalafil to tacrolimus. Serial follow-up of immunosuppressive-naïve TAK (n = 16) showed reduction in serum IL-6 and TGF-β1 (p < 0.05) and IL-6 in culture supernatant (p < 0.05) following immunosuppressive therapy., Conclusion: Novel Th17 sub-populations (Th17.1 and PD1+Th17) are elevated in TAK. Th17 lymphocytes associate with active TAK. In-vitro experiments on cultured PBMCs suggest promise for further evaluation of a combination of immunosuppressive tacrolimus with anti-fibrotic tadalafil (or other anti-fibrotic therapies) in clinical trials of TAK., Competing Interests: Dr Durga Prasanna Misra reports grants from Indian Council of Medical Research, during the conduct of the study. The authors report no other potential conflicts of interest in this work., (© 2022 Singh et al.)

Objective: To assess adequacy of present means of clinical communication between physicians and (Covid-19) patients' family members, to analyse their perspectives and recommend felicitous practices for virtual conversation during ongoing pandemic., Methods: Cross-sectional questionnaire-based (20 questions) anonymous online survey was conducted including patient's relatives (Group-1) and treating physicians (Group-2), through Google Forms., Results: Response Rate was 82.5%. Group-1 and Group-2 included 155 and 204 respondents respectively. Group-1 preferred update by resident doctors (39%), twice a day (41.9%), daily case-summaries (80%) and hand-written document/electronic messages (53%,31%) as consent. Whereas Group-2 favored update by senior consultants (63%), daily one appraisal (55.9%) and scanned copies of hand written consent (81%) before high-risk procedures. The groups broadly agreed on the desired duration for a fruitful discussion (5-10 min) and designating one responsible person from the family for daily appraisal., Conclusion: Use of modern techniques/technologies of communication (voice/video calls, texts) during the ongoing pandemic is acceptable to majority., Practice Implications: Study proposes a senior physician should communicate to a designated responsible family member at-least once a day for stable and twice a day for critical covid patients (more if patient's health condition changes), either by voice or video calls for 5-10 min., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Background: Sleep apnea (SA) is highly prevalent in acromegaly. Ethnicity influences the prevalence of SA in the general population. We studied the prevalence of SA and other respiratory comorbidities in North Indian patients with active acromegaly., Design: Prospective, observational., Materials and Methods: Consecutive adult patients with active acromegaly (n = 35, age 39.7 ± 13.2 years) and hypersomatotropism (nonsuppression of serum growth hormone after oral glucose and elevated serum insulin-like growth factor-1 [IGF-1]) were evaluated for respiratory symptoms, scoring for SA (Epworth Sleepiness Score [ESS] and STOP-BANG), pulmonary function tests (PFT), high-resolution computerized tomography (HRCT) of the thorax, polysomnography (PSG), and transthoracic echocardiography. Age- and sex-matched healthy individuals (n = 34) served as controls., Results: Acromegaly subjects had dyspnea (34%), cough (37%), excessive daytime somnolence (43%), and fatigue (49%). Clinically significant ESS (>10) and STOP-BANG score (≥3) were present in 41% and 68.6% of subjects, respectively. PFT showed restrictive and obstructive patterns in 45.7% and 11.4% of acromegalics respectively; with higher total lung capacity (TLC), thoracic gas volume (TGV), and residual volume (RV). PSG revealed significantly higher SA events in acromegalics (central [acromegaly 24.63 ± 37.82 vs. control 3.21 ± 5.5], mixed [11 ± 19.46 vs. 3.50 ± 5.96], obstructive [34.86 ± 44.37 vs. 9.71 ± 10.48], and mean apnea-hypopnea index [AHI] [16.91 ± 18.0 vs. 7.86 ± 7.84]). Acromegalics had significantly higher prevalence of obstructive SA (71.4% [mild 31.4%, moderate 20%, severe 20%]) as compared to controls (38.2%). There was no correlation of AHI with serum IGF-1 and disease duration., Conclusion: Acromegaly subjects have a significantly higher prevalence of respiratory symptoms, SA, and abnormalities in PFT. Screening for respiratory comorbidities should be routinely recommended in all patients with acromegaly., Competing Interests: None

Background: Knowledge of underlying pathophysiology of coagulopathy is evolving and the pattern of coagulation parameters in coronavirus disease 2019 (COVID-19)-associated diseases is still not very clear., Aims: In the present study, we aimed to find out the pattern and distribution of conventional coagulation parameters and thromboelastographic (TEG) parameters in COVID-19-associated coagulopathy (CAC) in survivors and nonsurvivors at 28 days., Setting and Design: The present prospective observational study was conducted at a tertiary care COVID-19 intensive care unit (ICU) facility from March 21, 2020, to July 15, 2021., Materials and Methods: Admission clinical and laboratory data (conventional coagulation, inflammatory and TEG parameters, and disease severity parameters) of 64 COVID-19 patients admitted to the ICU were collected. Patients were divided into two groups, i.e., survivors and nonsurvivors., Statistical Analysis: Data were compared between two groups, i.e., survivors versus no survivors on 28 days using Student's t -test/Mann-Whitney U-test or Chi-square test/Fisher's exact test., Results: Admission mean plasma fibrinogen levels (474.82 ± 167.41 mg.dL -1 ) and D-dimer were elevated (1.78 [0.66, 3.62] mg.mL -1 ) in the COVID-19 ICU patients. Overall, COVID-19 patients had mean lower normal platelet count (150 ± 50 × 10 3 cells.mm -3 ), with marginally elevated prothrombin time (16.25 ± 3.76 s) and activated partial thromboplastin time (38.22 ± 16.72 s). A 65.6% (42/64) TEG profile analysis showed a normal coagulation profile, and the rest 21.9% (14/64) and 12.5% (8/64) had hypercoagulable and hypocoagulable states, respectively. Plasma D-dimer level was markedly elevated in nonsurvivors compared to survivors ( P < 0.05), while no other conventional coagulation parameters and TEG profile demonstrated statistically significant between the two groups., Conclusion: Markedly elevated plasma D-dimer level was observed in nonsurvivors of COVID-19 ICU patients. A large portion of COVID-19 ICU patients had a normal TEG profile. Conventional coagulation parameters and TEG profile were similar between survivors and nonsurvivors., Competing Interests: There are no conflicts of interest., (Copyright: © 2022 Anesthesia: Essays and Researches.)

Background: Endobronchial ultrasound guided transbronchial needle aspiration (EBUS-TBNA) allows precise real-time sampling of intrathoracic lesions and is a minimally invasive, safe, and cost effective technique with high diagnostic yield. The aim of the current study is to evaluate utility of EBUS-TBNA cytology with cellblocks (CBs) in the diagnosis and subtyping of the intrathoracic lesions., Materials and Methods: It was a prospective study conducted from October 2015 to October 2017. We received 233 cases of intrathoracic lesions for EBUS-TBNA, of which CB was made in 217 cases. A flexible endobronchial ultrasound scope was used to sample the lesions., Results: There were 89 females and 128 males amongst the total 217 patients (age range: 14-85 years, mean age: 48.35 years). The smears from EBUS-TBNA contained adequate material in 137/144 [95.1%] non-neoplastic cases and 34/36 [94.4%] of the neoplastic cases, whereas the CBs provided adequate material in 94/144 [65.3%] non-neoplastic cases and 37/40 [92.5%] neoplastic cases. The CB helped subtyping the malignancy in 19 cases and of these immunohistochemistry (IHC) was done on the CB in 15 cases. The biopsy was non-diagnostic in 17/36 cases of granulomatous pathology and 4/18 neoplastic cases diagnosed with EBUS-TBNA.3., Conclusions: EBUS-TBNA provides rapid diagnosis through cytology and the material recovered in the same setting for the CB preparation can be used for immunohistochemical analysis and it may at times provide the diagnosis in cases where the smears are non-diagnostic., Competing Interests: There are no conflicts of interest., (Copyright: © 2021 Journal of Cytology.)

Objectives: We aim to define the burden of rifampicin monoresistant tuberculosis (TB) at a tertiary care centre in northern India as well as determine the second-line drug susceptibilities (SL-DST) in a subset of patients., Methods: A total of 3045 pulmonary (n=1883) and extrapulmonary (n=1162) samples from likely patients with TB were subjected to microscopy, culture and the Xpert MTB/RIF assay from March 2017 to June 2019. SL-DST testing by line probe assay version 2 for fluoroquinolones (FQs) and second-line injectable drugs were performed on 62 samples., Results: Out of 3045 samples processed in our laboratory during the study period, 36.1% (1101/3045) were positive for Mycobacterium tuberculosis complex (MTBC) and 21.6% were rifampicin monoresistant (223/1032). The rate of rifampicin resistance in pulmonary samples was 23.5% (166/706) and in extrapulmonary cases, it was 17.4% (57/326). Out of 62 cases included for second-line testing, 48 were resistant to FQs (77.4%) while 11 were extensively drug resistant., Conclusions: India urgently needs to arrest an emerging multidrug-resistant TB epidemic with associated resistance to FQs. A robust surveillance system is needed to execute the National Strategic Plan for 2017-2025., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Competing Interests: None

Introduction: Resistance to corticosteroid is an essential mechanism in uncontrolled asthma as the corticosteroid is the mainstay of therapy. There are recent reports that epigenetic factors play a crucial role in the regulation of steroid action. Overexpression of P glycoprotein (P-gp) and reduced expression of Histone Deacetylase 2 (HDAC2) have been linked to regulating the steroid action in other diseases like Nephrotic Syndrome (NS). However, their role in uncontrolled asthma is still not clear and warrants further investigation. We evaluated the expression and activity of P-gp and HDAC2 in patients with Controlled Asthma (CA) and Uncontrolled Asthma (UA)., Methods: A total of 60 CA (mean age 51.72±17.02 years, male=38), and 38 of UA (mean age=53.55±11.90 years, male=17) were recruited. The level of control was defined according to (Global Initiative for Asthma) GINA 2016 criteria. The mRNA expression of HDAC2 and P-gp was studied by quantitative real-time Polymerase Chain Reaction (PCR), the functional activity of P-gp was evaluated by a commercially available kit via flow cytometry, and HDAC2 enzymatic activity was measured by commercially available kit by Enzyme-Linked Immunosorbent Assay (ELISA)., Results: P-gp expression and the functionality were significantly higher in the UA group of patients as compared to the CA group of patients (p<0.005), moreover HDAC2 expression was significantly reduced in UA patients as compared to CA patients, (p<0.005). The enzymatic activity of HDAC2 was also significantly reduced in UA patients as compared to CA patients (p<0.005)., Conclusion: P-gp overexpression and HDAC2 under expression play an essential role in uncontrolled asthma by impairing the response to corticosteroid., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Introduction: We prospectively studied the frequency, spectrum, and predictors of gastrointestinal (GI) symptoms among patients with coronavirus disease-19 (COVID-19) and the relationship between GI symptoms and the severity and outcome., Methods: Consecutive patients with COVID-19, diagnosed in a university hospital referral laboratory in northern India, were evaluated for clinical manifestations including GI symptoms, their predictors, and the relationship between the presence of these symptoms, disease severity, and outcome on univariate and multivariate analyses., Results: Of 16,317 subjects tested for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) RNA in their oropharyngeal and nasopharyngeal swabs during April-May 2020, 252 (1.5%) were positive. Of them, 208 (82.5%) were asymptomatic; of the 44 symptomatic patients, 18 (40.9%) had non-GI symptoms, 15 (34.1%) had a combination of GI and non-GI symptoms, and 11 (25.0%) had GI symptoms only. Thirty-three had mild-to-moderate disease, 8 severe, and 5 critical. Five patients (1.98%) died. On multivariate analysis, the factors associated with the presence of GI symptoms included the absence of contact history and presence of non-GI symptoms and comorbid illnesses. Patients with GI synptoms more often had severe, critical illness and fatal outcome than those without GI symptoms., Discussion: Eighty-two percent of patients with COVID-19 were asymptomatic, and 10.3% had GI symptoms; severe and fatal disease occurred only in 5% and 2%, respectively. The presence of GI symptoms was associated with a severe illness and fatal outcome on multivariate analysis. Independent predictors of GI symptoms included the absence of contact history, presence of non-GI symptoms, and comorbid illnesses.(Equation is included in full-text article.).

Background: Tracheobronchial stenting either alone or with esophageal stenting is often required for symptom palliation in obstructive or fistulous lesions of the airway due to esophageal cancer. There is limited evidence regarding dual stenting for lesions near the carina due to esophageal cancer. Hence, this study aims to evaluate the technical feasibility, outcomes, and complications of preplanned dual stenting in these patients., Methods: This is a prospective observational study carried out over a period of 4 years (January 2015 to July 2019). All patients undergoing dual stenting in the airway and esophagus with obstructive or fistulous lesions near the carina were included. The esophageal stent was placed within 24 hours. Prestenting and poststenting symptoms were compared using a symptom-based visual analog scale, Hugh Jones dyspnea scale and dysphagia scale., Results: Twenty-nine patients (20 males; mean±SD age, 55.3±12.2 y) underwent dual stenting. Twenty-four patients had central airway obstruction due to: infiltration in 20 (69%) and external compression in 4 (13.7%), respectively. Five (17.3%) patients had tracheoesophageal fistula with no airway obstruction. In 80% of the patients (n=23), silicone stents were placed. There was significant improvement in both dyspnea and dysphagia after dual stenting (P<0.001). Mucus plugging, lower respiratory infection, and granulation tissue were the main complications. Median survival after dual stent was 97 days (range, 17 to 297 d)., Conclusion: Dual stenting within the airway and the esophagus is a safe and viable option for palliative relief of symptoms in patients with advanced esophageal cancer.

Background: The objective of the study was to assess T-cell subsets in sarcoidosis patients with or without articular involvement., Methods: Treatment-naïve patients were divided into Group A (articular) and Group B (non-articular) based on joint involvement. Flow cytometric analysis of T-cell subsets and pro-in˜flammatory cytokines were carried out in the peripheral blood., Results: Patients in group A (n = 29, mean age 40 ± 10.1 years) were compared with group B (n = 18, 43 ± 12.2 years). T-cell subsets: the CD4/CD8 ratio was abnormal in two groups but had no significant difference (p = 0.63). Ratios of Th1/Treg, Th2/Treg and Th17/Treg were significantly increased in group A as compared to group B [p < 0.001] indicating polarisation of T-cell subsets. CD8 T-cells in group A had higher granzyme B expression (p = 0.03). B cells were increased in group A [p = 0.04]. Ratio of IFN-γ /IL10, IL-4/IL10, IL-17/IL10 in sera as well as culture supernatant were significantly higher in group A as compared to group B., Competing Interests: No conflict of interests declared

Objective: P-glycoprotein (PGP) overexpression may be one of the operating mechanisms of suboptimal responses to antitubercular treatment (ATT) in patients with lymph node tuberculosis. This might become responsible for the development of drug resistance later due to exposure of subtherapeutic concentrations to the mycobacteria. In this study we aim to study the prevalence of PGP expression and function and its relationship with serum concentrations of Rifampicin in consecutive patients with lymph node tuberculosis., Methods: All newly diagnosed treatment naïve subjects with a confirmed diagnosis of tubercular lymphadenopathy were included in the study and the expression and function of PGP in blood was determined by flowcytometry at baseline and after two months of treatment. Serum levels of Rifampicin was measured at 2 months by high performance liquid chromatography (HPLC). The mean net PGP expression expressed as percent and relative fluorescence indices (RFI) of PGP expression and function respectively was compared at baseline at 2 months and was also correlated with serum rifampicin levels., Results: The mean net PGP expression, RFI of PGP expression and RFI of PGP function were significantly higher in patients with lymph node tuberculosis as compared to healthy controls and the mean net PGP expression and RFI of PGP expression were significantly higher at 2 months as compared to baseline (25.64 ± 5.18% vs. 27.68 ± 4.89%, 4.34 ± 1.09% vs. 4.95 ± 1.55). There was no significant difference in RFI of PGP expression and RFI of PGP function between the poor-responders and responders at baseline and 2 months however there was a trend towards significantly higher net PGP expression amongst poor responders at baseline. The mean serum rifampicin levels were 10.74 ± 2.36 μg/ml in the responder group and 7.86 ± 1.21 μg/ml in the non-responder group and the difference between the two was statistically significant (p = 0.004)., Conclusions: Overexpression of PGP is common in patients with lymph node tuberculosis and leads to lower concentrations of Rifampicin in blood which subsequently may give rise to development of drug resistance. This is also responsible for poor therapeutic responses in these patients. Nonspecific inhibitors of PGP may be used in conjunction with ATT to augment therapeutic response in such cases., Competing Interests: Conflicts of interest The authors have none to declare., (Copyright © 2019 Tuberculosis Association of India. Published by Elsevier B.V. All rights reserved.)

Context: Few studies have been done for correlating asthma severity, IgE level, and spirometry results with high-resolution computed tomographic (HRCT) findings in allergic bronchopulmonary aspergillosis (ABPA)., Aims: This prospective observational study was conducted to correlate asthma severity, IgE level, and spirometry results with HRCT findings in ABPA., Settings and Design: Prospective observational., Subjects and Methods: Fifty consecutive adult patients with asthma and positive specific IgE (>0.35 kUA/L) to Aspergillus fumigatus were recruited from October 2015 to July 2017. Asthma severity, IgE levels, and spirometry results were correlated with HRCT score, bronchiectasis score, air trapping segments, and low-attenuation lung volume on inspiratory CT and expiratory CT., Statistical Analysis Used: One way ANOVA, Spearman's correlation coefficients., Results: Asthma severity showed a significant positive correlation with HRCT score and bronchiectasis score. MEF pre and postbronchodilator values showed a significant negative correlation with HRCT score, bronchiectasis score, and percentage expiratory volumes -851 to -950 HU voxels. FEV1 prebronchodilator value showed a significant negative correlation with percentage expiratory volume -851 to -950 HU voxels and percentage expiratory volume -851 to -1024 HU voxels. Specific IgE antibody level showed a significant positive correlation with bronchiectasis score., Conclusions: Asthma severity, specific IgE level, and MEF values showed a good correlation with HRCT findings. The restrictive pattern is common on spirometry in patients of ABPA. In addition to central bronchiectasis, peripheral bronchial and small airway involvement was an important finding in ABPA. Expiratory HRCT may reveal air trapping in patients having no abnormality on inspiratory CT., Competing Interests: There are no conflicts of interest., (Copyright: © 2020 Indian Journal of Radiology and Imaging.)

Objective: The aim of this study was to assess the diagnostic yield of robotic-assisted computed tomography (CT)-guided F-FDG PET/CT-directed biopsy for the evaluation of intrathoracic space occupying lesions., Methods: Twenty-four patients being evaluated for intrathoracic masses were included in the study. The indications were patients with unknown/likely primary detected from PET-CT, suspicious lesions identified from PET-CT in a known primary disease and fine needle aspiration cytology/CT-guided biopsy negative lesions with a high index of suspicion for malignancy. Biopsies were carried out with the help of automated radiology arm (ROBIO-EX) which is essentially a needle positioning and holding device. A two-day protocol was followed in which PET-CT scan was done on the first day, biopsy procedure was done on the next scheduled day. PET images were refused with the CT images done on the second day in the console by using manual alignment and then a biopsy was carried out with the help of a robotic arm. Primary outcome was histopathological yield from the obtained specimens., Results: Tissue yield was 100% (n = 24) and histopathological diagnosis rate was 96% (n = 23). Out of the 24 lesions biopsied 30% (n = 8) were benign and 70% (n = 16) turned out to be malignant. The complication rates were pneumothorax 4% (n = 1) and haemothorax 4% (n = 1)., Conclusion: Robotic-assisted CT-guided F-FDG PET/CT-directed biopsy is a useful and accurate technique for diagnostic evaluation of intrathoracic neoplasms with minimal complications rates as compared with conventional imaging techniques.

Background: Central airway obstruction (CAO) is a significant cause of morbidity and mortality in patients with thoracic malignancies. In this prospective study, we describe the role of rigid bronchoscopy (RB) in the multimodality management of CAO., Methods: Prospective description of different rigid bronchoscopic techniques used for CAO between July 2016 and July 2019., Results: A total of 152 procedures (124 therapeutic/palliative and 28 diagnostics) in 111 adults and 10 pediatric patients were performed. The mean age in 111 adults (66 males) and 10 pediatric (5 males) patients were 45.4 ± 15.8 (range 16-80) and 5.4 ± 3.6 (range 1-10) years, respectively. Palliation of the airway obstruction (48.8%) and establishment of diagnosis (23.2%) were the main indications of RB in our study. Mechanical debulking in 53 (57%) and airway dilatation in 40 (43%) patients were the most utilized interventions during the palliative or therapeutic RB. There was a significant decrease in mean (modified Medical Research Council) dyspnea scale from 3.9 ± 1.0 to 1.42 ± 0.63 and increase in mean Visual Analogue Scale from 2.06 ± 0.74 to 8.7 ± 0.54 after the procedure (P < 0.0001). Additional therapy was undertaken in 38 (31.4%) of 121 patients, and surgical excision was the primary form of definitive treatment in 17 patients Moderate bleeding was encountered in 13.3% of the procedures mainly in the diagnostic RB. The mean procedure duration was 28.4 (range, 11-49) min and 13.2 (7-22) min in the adults and pediatric patients, respectively. A total of 31 patients succumbed to the illness due to the progressive nature of their disease., Conclusions: An individualized approach to interventional procedures is safe and effective way to achieve and maintain palliation of CAO. RB with multimodality treatment achieves the goal in majority of the patients., Competing Interests: None

Changes in expression of membrane antigens may accompany the transition of Mycobacterium tuberculosis (Mtb) from 'dormant' to 'active' states. We have determined whether antibody and T cell responses to Mtb membrane (MtM)-associated antigens, especially the latency-induced protein alpha crystallin (Acr), can discriminate between latent tuberculosis infection (LTBI) and active TB (ATB) disease. Study subjects comprised a previously described cohort of healthcare workers (HCWs, n = 43) and smear-positive ATB patients (n = 10). HCWs were further categorized as occupational contacts (OC, n = 30), household contacts of TB (HC, n = 8) and cured TB (CTB, n = 5). Levels (ΔOD) of serum antibody isotypes (IgG, IgA and IgM) were determined by ELISA and blood T cell proliferative responses were determined by flow cytometry using Ki67 protein as marker for DNA synthesis. Antibodies to MtM and Acr were predominantly IgG and their levels in HCWs and ATB did not differ significantly. However, HCWs showed a significantly higher level of anti-MtM IgM and a significantly lower level of anti-Acr IgA antibodies than the ATB patients. Also, a larger proportion of HCWs showed a high (>1) ΔODAcr/ΔODMtM ratio for IgG. HCWs also showed a higher, though not significantly different from ATB, avidity of anti-MtM (IgG) antibodies. A higher proportion of HCWs (35% of OC, 62.5% of HC and 20% of CTB), compared with ATB (10%) showed a positive T cell response to Acr along with significant difference (P <0.05) between HC and ATB. A significant correlation (r = 0.60, P <0.0001) was noted between T cell responses of HCWs towards Acr and MtM (reported earlier by us) and both responses tended to decline with rising exposure to the infection. Even so, positive responses to Acr (38.5%) were significantly lower than to MtM (92%). Neither antibody nor T cell responses to either antigen appeared affected by BCG vaccination or reactivity to tuberculin. Results of the study suggest that the levels of IgM antibodies to MtM, IgA antibodies to Acr and proliferative T cell responses to both the antigens can potentially discriminate between LTBI and active TB disease. They also underscore the necessity of SOPs for antibody assays., Competing Interests: The authors have declared that no competing interests exist.

Objective: Non-resolving consolidation (NRC) with inconclusive sputum, bronchoscopy, and bronchoalveolar lavage results poses a diagnostic dilemma. This retrospective analytical study was conducted to evaluate diagnostic yield and complications of percutaneous computed tomography (CT)-guided lung biopsy (PCLB) in NRC. Assessment of clinical features and high-resolution CT (HRCT) characteristics was also done which may predict outcome., Materials and Methods: Data of PCLB performed for lung consolidation from January 2010 to January 2019 were retrospectively evaluated. For the determination of diagnostic yield, a positive result from any one specimen obtained by PCLB (tissue core, aspiration cytology, or microbiology) was sufficient to considered procedure diagnostic if it was concordant with clinical features, imaging findings, response to treatment, and subsequent follow-up. Student's t -test and Fisher's exact test were used for statistical analysis., Results: Out of total 56 patients, final diagnosis was achieved in 48 (19 malignant and 29 benign). Diagnostic yield was 69.6%. Complications were noted in 10 patients including mild hemoptysis and pneumothorax, which were managed conservatively. No clinical feature was having statistically significant association with final diagnosis. HRCT findings significantly associated with malignant outcome were larger size of consolidation, multiple contiguous lobe involvement, multiple air-filled cysts inside consolidation, and associated ground-glass areas or multiple ground-glass nodules. The absence of air bronchogram was more common in benign cases., Conclusion: PCLB is a safe and useful method for obtaining specimen in NRC. Differentiation of benign from malignant outcome is not possible based on clinical findings; however, certain HRCT findings raise suspicion of malignancy., Competing Interests: There are no conflicts of interest., (© 2019 Published by Scientific Scholar on behalf of Journal of Clinical Imaging Science.)

Context: Obstructive sleep apnea (OSA) considered classically to be a male-dominant disease, may have significant gender-based differences in clinical presentation and diagnosis., Aims: To evaluate gender-based differences in the clinical profile and polysomnographic features of Indian patients with OSA., Settings and Design: A prospective observational study was conducted over a period of 12 months involving adult ambulatory patients, referred for evaluation of OSA., Methods and Materials: Enrolled patients underwent detailed clinical evaluation followed by supervised polysomnography. Sleep studies were manually validated and analyzed., Statistical Analysis Used: Continuous variables were compared using two-tailed independent- sample t -test. For the univariate analysis, the Chi-square test was used., Results: Out of 150 enrolled patients, 94 (62.7%) were males (male-to-female: 1.7:1; age: 51.85 ± 12.60 years; BMI: 32.09 ± 5.53 kg/m 2 ). Most common presenting features were excessive daytime somnolence, snoring, and easy fatiguability. Women with OSA were older than men. Insomnia and anxiety were significantly higher among females. Parameters defining sleep architecture were similar in both groups. Although obstructive apneas and hypopneas were similar, mean apnea hypopnea index was significantly higher ( P < 0.05) in males compared to females with higher titratable continuous positive airway pressure., Conclusions: There are gender-specific differences in the clinical presentation of OSA due to various anatomical, physiological, and psychosocial factors. Their potential influence on the clinical features, natural history, and implications on treatment need further evaluation on a larger scale., Competing Interests: There are no conflicts of interest., (Copyright: © 2019 Journal of Family Medicine and Primary Care.)

Flexible bronchoscopy (FB) is commonly performed by respiratory physicians for diagnostic as well as therapeutic purposes. However, bronchoscopy practices vary widely across India and worldwide. The three major respiratory organizations of the country supported a national-level expert group that formulated a comprehensive guideline document for FB based on a detailed appraisal of available evidence. These guidelines are an attempt to provide the bronchoscopist with the most scientifically sound as well as practical approach of bronchoscopy. It involved framing appropriate questions, review and critical appraisal of the relevant literature and reaching a recommendation by the expert groups. The guidelines cover major areas in basic bronchoscopy including (but not limited to), indications for procedure, patient preparation, various sampling procedures, bronchoscopy in the ICU setting, equipment care, and training issues. The target audience is respiratory physicians working in India and well as other parts of the world. It is hoped that this document would serve as a complete reference guide for all pulmonary physicians performing or desiring to learn the technique of flexible bronchoscopy., Competing Interests: None