Antioxidant therapies for obstructive sleep apnea: A systematic review and meta-analysis.

PURPOSE: Obstructive sleep apnea (OSA) is a common clinical problem that is associated with adverse cardiovascular outcomes attributed to the oxidative stress due to sympathetic overstimulation. Treatment approaches targeting oxidative stress have been tried by multiple investigators. This systematic review and meta-analysis evaluated the efficacy and safety of such approaches. METHODS: Pubmed and Embase databases were searched for human studies evaluating the utility of antioxidant therapies in patients with OSA. RESULTS: A total of six studies (five randomized trials and one case-control study) were included, including 160 patients with OSA using N-acetyl cysteine, vitamin C, carbocysteine, superoxide dismutase, vitamin E, allopurinol, and their combinations. There was a significant improvement in flow-mediated dilatation (FMD) following antioxidants, with the pooled effect being 2.16 % (95% CI 1.65-2.67) using the random-effects model (I2 = 0% and p<0.001). It was also associated with a significant reduction in malondialdehyde levels and an increase in reduced glutathione (GSH) levels. There was also a significant improvement in the Epworth sleepiness scale, oxygen desaturation index, and minimum oxygen saturation during sleep without any significant adverse effects. CONCLUSION: Antioxidant therapy in patients with OSA is associated with improved endothelial function, reduced oxidative stress, and improved sleep parameters. These results call for future multicentre studies with longer follow-ups to assess the utility of antioxidant therapy in patients with OSA.

A multicentre, double-blind, placebo-controlled randomized trial of Mycobacterium w in critically ill patients with COVID-19 (ARMY-2).

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].

Clinical Features Predicting COVID-19 Severity Risk at the Time of Hospitalization.

The global spread of COVID-19 has led to significant mortality and morbidity worldwide. Early identification of COVID-19 patients who are at high risk of developing severe disease can help in improved patient management, care, and treatment, as well as in the effective allocation of hospital resources. The severity prediction at the time of hospitalization can be extremely helpful in deciding the treatment of COVID-19 patients. To this end, this study presents an interpretable artificial intelligence (AI) model, named COVID-19 severity predictor (CoSP) that predicts COVID-19 severity using the clinical features at the time of hospital admission. We utilized a dataset comprising 64 demographic and laboratory features of 7,416 confirmed COVID-19 patients that were collected at the time of hospital admission. The proposed hierarchical CoSP model performs four-class COVID severity risk prediction into asymptomatic, mild, moderate, and severe categories. CoSP yielded better performance with good interpretability, as observed via Shapley analysis on COVID severity prediction compared to the other popular ML methods, with an area under the received operating characteristic curve (AUC-ROC) of 0.95, an area under the precision-recall curve (AUPRC) of 0.91, and a weighted F1-score of 0.83. Out of 64 initial features, 19 features were inferred as predictive of the severity of COVID-19 disease by the CoSP model. Therefore, an AI model predicting COVID-19 severity may be helpful for early intervention, optimizing resource allocation, and guiding personalized treatments, potentially enabling healthcare professionals to save lives and allocate resources effectively in the fight against the pandemic.

Retrospective application of WHO reporting system for lung cytopathology with assessment of risk of malignancy.

INTRODUCTION: The recently introduced World Health Organization (WHO) Reporting System for Lung Cytopathology presents 5 diagnostic categories with corresponding risk of malignancy (ROM) and management protocols. This study uses the system to categorize our institutional respiratory tract cytology specimens, evaluating ROM and diagnostic accuracy for each category. MATERIALS AND METHODS: In a retrospective analysis (May 2020 to August 2021), the following respiratory cytology specimens were classified based on the WHO categories: bronchoalveolar lavage (BAL), bronchial wash/bronchial brushings (BB/BW), endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA), fine-needle aspiration cytology (FNAC), sputum, biopsy imprint (BI), and endotracheal wash. Exclusions comprised pleural effusions and EBUS-TBNA from mediastinal and hilar lymph nodes. Correlation of cytologic and histopathologic diagnoses was performed to assess ROM collectively and individually. RESULTS: A total of 1518 respiratory samples (BAL [968], BW/BB [380], EBUS-TBNA [42], FNAC [32], sputum [80], BI [11] and endotracheal wash [5]) of 1410 patients were screened, of which 522 cases (34.3%) had histopathologic correlation. One hundred forty-one cases (9.3%) were Insufficient/Inadequate/Non-Diagnostic (ND), 1221 (80.4%) were Benign (B), 3 (0.2%) were Atypical (A), 32 (2.1%) were Suspicious for malignancy (SM) and 121 (8.0%) were Malignant (M). The estimated ROM for each category was 49.2% for ND, 13.3% for B, 66.6% for A, 81.5% for SM and 92.7% for M. FNAC and EBUS-TBNA exhibited the highest sensitivity (100%) compared with BW/BB (66.3%). Specificity ranged from 96.8% to 100% across the samples, while diagnostic accuracy varied from 58.8% to 100%. CONCLUSIONS: Application of the WHO reporting system enhances standardized terminology, aiding clinicians in informed decision-making and improving patient care through accurate risk assessment of malignancy.

Revised ISHAM-ABPA working group clinical practice guidelines for diagnosing, classifying and treating allergic bronchopulmonary aspergillosis/mycoses.

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.

Hyperglycemia modulates M1/M2 macrophage polarization in chronic diabetic patients with pulmonary tuberculosis infection.

Increased susceptibility to bacterial infections like tuberculosis (TB) is one of the complications of type 2 diabetes, however the underlying mechanisms remains poorly characterized. To explore how chronic hyperglycemia in diabetes affects progression of active TB, we examined mRNA expression of M1 (proinflammatory) and M2 (anti-inflammatory) cytokines/markers, in monocyte-derived macrophages obtained from patients with PTB + DM (pulmonary TB + diabetes mellitus type 2), patients with DM alone, patients with PTB alone, and healthy individuals (controls). Our findings indicate a dysregulated cytokine response in patients with both PTB and DM, characterized by decreased expression levels of interferon-gamma (IFN-γ) and inducible nitric oxide synthase (iNOS), along with increased expression levels of interleukin-1 beta (IL-1ß) and CD206. Furthermore, we observed a positive correlation of IL-1ß and CD206 expression with levels of glycosylated hemoglobin (HbA1c) in both PTB + DM and DM groups, while IFN-γ showed a positive correlation with HbA1c levels, specifically in the PTB + DM group. Additionally, M1 cytokines/markers, IL-1ß and iNOS were found to be significantly associated with the extent of sputum positivity in both PTB and PTB + DM groups, suggesting it to be a function of increased bacterial load and hence severity of infection. Our data demonstrates that tuberculosis in individuals with PTB + DM is characterized by altered M1/M2 cytokine responses, indicating that chronic inflammation associated with type 2 diabetes may contribute to increased immune pathology and inadequate control of tuberculosis infection.

Association of Leukocyte Subpopulations Identified by Flow Cytometry with Outcomes of Sepsis in a Respiratory Intensive Care Unit: An Observational Study.

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.

Concordance of Immunohistochemistry and Fluorescence In Situ Hybridization in the Detection of Anaplastic Lymphoma Kinase (ALK) and Ros Proto-oncogene 1 (ROS1) Gene Rearrangements in Non-Small Cell Lung Carcinoma: A 4.5-Year Experience Highlighting Challenges and Pitfalls.

CONTEXT.­: ALK and ROS1 rearrangements are essential biomarkers to be tested in advanced lung adenocarcinomas. While D5F3 Ventana assay is a companion diagnostic for anaplastic lymphoma kinase-targeted therapy, immunohistochemistry is only a screening tool for detecting ROS1 rearrangement. Confirmation by cytogenetic or molecular techniques is necessary. OBJECTIVE.­: To evaluate the utility of ALK and ROS1 fluorescence in situ hybridization as a complement to immunohistochemistry in routine predictive biomarker testing algorithms. DESIGN.­: The study was ambispective, spanning 4.5 years during which lung adenocarcinoma samples were subjected to EGFR mutation testing by real-time polymerase chain reaction, and ALK/ROS1 rearrangement testing by immunohistochemistry (Ventana D5F3 assay for anaplastic lymphoma kinase protein; manual assay with D4D6 clone for Ros proto-oncogene 1 protein). Fluorescence in situ hybridization was performed in all anaplastic lymphoma kinase equivocal and Ros proto-oncogene 1 immunopositive cases. RESULTS.­: Of 1874 samples included, EGFR mutations were detected in 27% (481 of 1796). Anaplastic lymphoma kinase immunohistochemistry was positive in 10% (174 of 1719) and equivocal in 3% (58 of 1719) of samples tested. ALK fluorescence in situ hybridization showed 81% (77 of 95) concordance with immunohistochemistry. Ros proto-oncogene 1 immunopositivity was noted in 13% (190 of 1425) of cases, with hybridization-confirmed rearrangements in 19.3% (26 of 135) of samples, all of which showed diffuse, strong- to moderate-intensity, cytoplasmic staining in tumor cells. Ros proto-oncogene 1 protein overexpression without rearrangement was significantly common in EGFR-mutant and ALK-rearranged adenocarcinomas. CONCLUSIONS.­: Immunostaining is a robust method for ALK-rearrangement testing, with fluorescence in situ hybridization adding value in the rare equivocal stained case. ROS1-rearrangement testing is more cost-effective if immunohistochemistry is followed by fluorescence in situ hybridization after excluding EGFR-mutant and ALK-rearranged adenocarcinomas.

Transoesophageal bronchoscopic ultrasound-guided fine-needle aspiration (EUS-B-FNA) for left adrenal gland (LAG) sampling: A report of three cases with a review of the literature.

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.

Effect of Metformin on Plasma Exposure of Rifampicin, Isoniazid, and Pyrazinamide in Patients on Treatment for Pulmonary Tuberculosis.

BACKGROUND: To evaluate the effect of metformin on the plasma levels of rifampicin, isoniazid, and pyrazinamide in patients with drug-sensitive pulmonary tuberculosis being treated with first-line antituberculosis treatment (ATT) and to assess the influence of gene polymorphisms on the metabolic pathway of metformin and plasma levels of antitubercular drugs. METHODS: Nondiabetic adults aged 18-60 years with pulmonary tuberculosis were randomized to either the standard ATT (ATT group) or ATT plus metformin (METRIF group) groups in a phase IIB clinical trial. An intensive pharmacokinetic study with blood collection at 0 hour (predosing), followed by 1, 2, 4, 6, 8, and 12 hours after dosing was conducted during the first month of treatment in a subset of 60 study participants after a minimum of 14 doses. Plasma concentrations of rifampicin, isoniazid, pyrazinamide, and metformin were measured by high-performance liquid chromatography using validated methods, and pharmacokinetic parameters and OCT1 and MATE1 gene polymorphisms were compared between the groups. RESULTS: Significant increases in the clearance of rifampicin, isoniazid, and pyrazinamide were observed in patients in the METRIF group (n = 29) compared with those in the ATT group (n = 31). The AA genotypes of the single-nucleotide polymorphism of rs2289669 (MATE1) in the METRIF group showed a significantly decreased area under the concentration-time curve to the last observation point and increased clearance of rifampicin. CONCLUSIONS: Metformin altered rifampicin and isoniazid plasma concentrations in patients receiving antituberculosis treatment for pulmonary tuberculosis with little effect on sputum conversion at the end of treatment. Studies with larger sample sizes are needed to understand host drug-drug interactions.

Prevalence of chronic obstructive pulmonary disease in Indian nonsmokers: a systematic review & meta-analysis.

INTRODUCTION: Nonsmokers with chronic obstructive pulmonary disease (COPD) are neglected despite constituting half of all cases in studies from the developed world. Herein, we systematically reviewed the prevalence of COPD among nonsmokers in India. CONTENT: We searched Embase, Scopus, and PubMed databases for studies examining the prevalence of COPD among nonsmokers in India. We used the Joanna Briggs Institute (JBI) checklist to assess included studies' quality. Meta-analysis was performed using random-effects model. SUMMARY: Seven studies comprising 6,903 subjects were included. The quality of the studies ranged from 5/9 to 8/9. The prevalence of COPD varied between 1.6 and 26.6 %. Studies differed considerably in demographics and biomass exposure profiles of subjects. Among the four studies that enrolled both middle-aged and elderly Indian nonsmokers not screened based on biomass fuel exposure, the pooled prevalence of COPD was 3 % (95 % CI, 2-3 %; I2=50.52 %, p=0.11). The pooled prevalence of COPD among biomass fuel-exposed individuals was 10 % (95 % CI, 2-18 %; I2=98.8 %, p<0.001). OUTLOOK: Limited evidence suggests a sizable burden of COPD among nonsmokers and biomass fuel-exposed individuals in India. More epidemiological studies of COPD in nonsmokers are needed from low and middle-income countries.

The Utility of Galactomannan and Polymerase Chain Reaction Assays in Bronchoalveolar Lavage for Diagnosis of Chronic Pulmonary Aspergillosis.

The diagnosis of chronic pulmonary aspergillosis (CPA) is established by combined clinic-radio-microbiological criteria. Out of the different microbiological criteria, a positive serology for Aspergillus-specific IgG levels is the cornerstone of diagnosis. Alternatively, other microbiological evidence are sometimes sought viz., positive Aspergillus antigen (broncho-alveolar lavage fluid, i.e., BALF galactomannan ≥ 1.0), histopathological demonstration of the fungi following lung biopsy or resection, demonstration of hyaline septate hyphae in direct microscopy resembling Aspergillus spp. or its growth on a respiratory specimen. However, the exact roles of BALF- GM and the newer BALF-PCR have not been confirmed by studies till date. This study enrolled 210 patients with suspected CPA. Of the participants, 88 patients met the criteria for CPA, whereas 122 patients had an alternative diagnosis. The sensitivity-specificity of AsperGenius® PCR and "in-house" PCR were 52.27(36.69-67.54) %-33.78 (23.19-45.72) % and 36.36 (22.41-52.23) %-39.19 (28.04-51.23) % respectively. The sensitivity/specificity of BALF (> 1.0) and serum galactomannan (> 1.0) were 46.55% (33.34-60.13)/64.08% (54.03-73.3) and 29.82% (22.05-37.6)/86.84% (81.1-92.59) respectively. The optimal cut-off values for BALF-Galactomannan and serum galactomannan in diagnosing CPA were found to be 0.69 (sensitivity: 64%; specificity: 53%) and 0.458 (sensitivity: 67%; specificity: 64%) respectively. This results of this study suggests that Aspergillus PCR from BAL may not be a good "rule-in" test for diagnosing CPA. While the performances of GM in BAL and serum may be better than PCR, it should be best used in conjunction with other clinical, radiological, and other microbiological characteristics.

Mortality in Two Waves of COVID-19: A Comparative Analysis of a Tertiary Care Hospital in India.

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.

Identification of molecular biomarkers associated with non-small-cell lung carcinoma (NSCLC) using whole-exome sequencing.

OBJECTIVES: Significant progress has been made in the treatment of patients with pulmonary adenocarcinoma (ADCA) based on molecular profiling. However, no such molecular target exists for squamous cell carcinoma (SQCC). An exome sequence may provide new markers for personalized medicine for lung cancer patients of all subtypes. The current study aims to discover new genetic markers that can be used as universal biomarkers for non-small cell lung cancer (NSCLC). METHODS: WES of 19 advanced NSCLC patients (10 ADCA and 9 SQCC) was performed using Illumina HiSeq 2000. Variant calling was performed using GATK HaplotypeCaller and then the impacts of variants on protein structure or function were predicted using SnpEff and ANNOVAR. The clinical impact of somatic variants in cancer was assessed using cancer archives. Somatic variants were further prioritized using a knowledge-driven variant interpretation approach. Sanger sequencing was used to validate functionally important variants. RESULTS: We identified 24 rare single-nucleotide variants (SNVs) including 17 non-synonymous SNVs, and 7 INDELs in 18 genes possibly linked to lung carcinoma. Variants were classified as known somatic (n= 10), deleterious (n= 8), and variant of uncertain significance (n= 6). We found TBP and MPRIP genes exclusively associated with ADCA subtypes, FBOX6 with SQCC subtypes and GPRIN2, KCNJ18 and TEKT4 genes mutated in all the patients. The Sanger sequencing of 10 high-confidence somatic SNVs showed 100% concordance in 7 genes, and 80% concordance in the remaining 3 genes. CONCLUSIONS: Our bioinformatics analysis identified KCNJ18, GPRIN2, TEKT4, HRNR, FOLR3, ESSRA, CTBP2, MPRIP, TBP, and FBXO6 may contribute to progression in NSCLC and could be used as new biomarkers for the treatment. The mechanism by which GPRIN2, KCNJ12, and TEKT4 contribute to tumorigenesis is unclear, but our results suggest they may play an important role in NSCLC and it is worth investigating in future.

Phenotypic Profiling of Immune Cells and Their Mediators in Chronic Obstructive Pulmonary Disease.

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.

Case report of SARS-CoV-2 with secondary Clostridioides difficile infection.

There has been an overuse of antibiotics in most patients suffering from COVID-19 which predisposes patients to hospital acquired C. difficile Infection (CDI). Also, COVID infection of the gastrointestinal tract also predisposes the patient to CDI. We here present a fatal case of SARS-CoV-2 coinfection with CDI.

T-cell signature cytokines distinguish pulmonary sarcoidosis from pulmonary tuberculosis.

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-ß)]. 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.

Systematic review and meta-analysis of the prevalence of obstructive sleep apnea in Indian adults.

Obstructive sleep apnea (OSA) is a common sleep disorder associated with considerable morbidity. However, there is an underrepresentation of data from India and other developing countries in global reviews of OSA prevalence. This systematic review and meta-analysis examined the prevalence of OSA in India. The MEDLINE, Embase, and Scopus databases were searched for articles that reported the prevalence of OSA in the general Indian adult population using sleep studies. Eight studies were included comprising 11,009 subjects with mean age ranging from 35.5 to 47.8 years. On the Joanna Briggs Institute (JBI) checklist for prevalence studies, the study quality ranged from 3/9 to 9/9. Meta-analysis was performed using the random-effects model. The pooled prevalence of OSA (AHI ≥5 events/hour) was 11% overall (95% CI: 7%-15%; I2 = 98.0%, p<0.001), 13% in males (95% CI: 7%-18%; I2 = 96.0%, p<0.001), and 5% in females (95% CI: 3%-7%; I2 = 73.3%, p = 0.01). The pooled prevalence of moderate-to-severe OSA (AHI ≥15 events/hour) was 5% (95% CI: 2%-8%, I2 = 95.3%; p = 0.01). Based on these findings, approximately 104 million Indians of working age suffer from OSA, of whom 47 million have moderate-to-severe OSA. This represents a major public health problem in India with important implications for the global burden of the disease.

The Evaluation of Laboratory Parameters as Predictors of Disease Severity and Mortality in COVID-19 Patients: A Retrospective Study From a Tertiary Care Hospital in India.

Background Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection affects and alters various laboratory parameters that are predictors of disease severity and mortality, and hence, their prompt identification can aid in patient triaging and resource allocation. Objectives A retrospective study was conducted on 7416 admitted coronavirus disease 2019 (COVID-19) patients from 20 March 2020 to 9 August 2021 to identify crucial laboratory biomarkers as predictors of disease severity and outcome; also, their optimal cutoffs were also calculated. A comparison of laboratory markers between both COVID-19 waves was also performed. Results The majority of patients had mild disease (4295/7416, 57.92%), whereas 1262/7416 (17.02%) had severe disease. The overall fatal outcome was reported in 461 (6.22%) patients. Predictors for mortality were age (>52 years), albumin/globulin (A/G) ratio (≤1.47), chloride (≤101 mmol/L), ferritin (>483.89 ng/mL), lactate dehydrogenase (LDH) (>393 U/L), procalcitonin (>0.10 ng/mL), interleukin-6 (IL-6) (>8.8 pg/mL), fibrinogen (>403 mg/dL), international normalized ratio (INR) (>1.18), and D-dimer (>268 ng/mL). Disease severity predictors were neutrophils (>81%), lymphocyte (≤25.4%), absolute lymphocyte count (ALC) (≤1.38×103/µL), absolute eosinophil count (AEC) (≤0.03×103/µL), total bilirubin (TBIL) (≥0.51 mg/dL), A/G ratio (≤1.49), albumin (≤4.2 g/dL), ferritin (≥445.4 mg/dL), LDH (≥479 U/L), IL-6 (≥28.6 pg/mL), C-reactive protein/albumin (CRP/ALB) ratio (≥1.78), D-dimer (≥237 ng/mL), and fibrinogen (≥425 mg/dL). The majority of patients admitted in the second wave were older and had severe disease, increased fatality, and significantly deranged laboratory parameters than first wave patients. Conclusion Our findings suggested that several biomarkers are crucial for both severe disease and mortality in COVID-19 patients. Ferritin, LDH, IL-6, A/G ratio, fibrinogen, and D-dimer are important biomarkers for both severity and mortality, and when combined, they provide valuable information for patient monitoring and triaging. In addition to these, older age, INR, chloride, and procalcitonin are also significant risk factors for mortality. For severe COVID-19, TBIL, CRP/ALB, albumin, neutrophil percentage, lymphocyte percentage, ALC, and AEC are also important biomarkers. According to the study, the majority of the baseline laboratory parameters associated with COVID-19 mortality and severe disease were significantly higher during the second wave, which could be one of the possible causes for the high mortality rate in India during the second wave. So, the combination of all these parameters can be a powerful tool in emergency settings to improve the efficacy of treatment and prevent mortality, and the planning of subsequent waves should be done accordingly.