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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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Purpose: Coronavirus disease 2019 (COVID-19) is purely a viral illness which is not affected by the usage of antibiotics, but the risk of development of secondary bacterial infections during the course of respiratory illness or hospitalisation has led to a surge of antibiotic use. Anti-microbial resistance has taken an upward trend to some of the commonly used or over-used antibiotics. The present study was planned to focus on the trends of resistance rates noticed for the common antibiotics, namely, doxycycline, azithromycin, and so on, before and after the advent of this pandemic. Material and Methods: The study was conducted at a tertiary care hospital of North India with 2000 samples, 1000 samples between March 2019 and March 2020 before the COVID pandemic and 1000 samples between April 2020 and April 2021 after the advent of the pandemic. Identification and zones for doxycycline and erythromycin were interpreted as per Clinical and Laboratory Standards Institute guidelines. Results: Among the various samples, pus/aspirated fluids were in majority (47%), followed by blood (29%), respiratory specimens (18%), and urine (6%). On stratifying the various pathogens associated with the treatment of doxycycline and erythromycin, Staphylococcus species were the predominant ones in almost 82% of the cases, followed by Enterococcus (12%) and Streptococcus (6%) species. For doxycycline, the overall sensitivity was noted to be 46% in the year 2019-20 and 31% in the year 2020-21, whereas for erythromycin, the sensitivity was seen as 39% in 2019-20 and dropped down to 26% in 2020-21. Conclusions: The authors noted a dip in the overall sensitivity towards doxycycline and azithromycin. This finding clearly indicates the increasing rates of antibiotic resistance in a developing country such as India during these COVID times. A proper anti-microbial stewardship programme during these times will help to de-escalate the increasing resistance rates and will prove to be of great help to the primary care physicians. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Background: Epigenetic factors play an essential role in regulating the action of steroids in asthma. Steroids suppress inflammation by recruiting histone deacetylase-2 (HDAC-2), which removes the acetyl group of the nuclear factor kappa B-enabled inflammatory gene complex and disables its action. P-glycoprotein (P-gp)/Multidrug resistance-associated protein 1 (MRP-1), the energy-dependent efflux pumps, reduces the bioavailability of steroids in the cell by pumping it out. The expression of P-gp/MRP-1 and HDAC-2 has been linked to regulating the action of steroids in asthma. Therefore, the use of HDAC-2 inducer like theophylline might improve asthma control by improving steroid responsiveness. Objective: HDAC-2 inducer, theophylline, can improve glucocorticoid responsiveness in severe uncontrolled asthma (UA). Materials and Methods: We classified subjects into severe UA (n = 7, age: 52.36 ± 11.94 years), controlled asthma (CA) (n = 23, age: 50.65 ± 16.11 years), and treatment-naïve patients (n = 10, age: 50.60 ± 14.38 years). Peripheral blood mononuclear cells (PBMCs) were isolated and treated with theophylline (1 μM) and Trichostatin-A (TSA) (0.8 μM) for 48 h, for induction/suppression of HDAC-2, respectively. The messenger RNA (mRNA) expression extracted from PBMCs was studied for HDAC-2and P-gp/MRP-1 by quantitative real-time polymerase chain reaction. Results: The mRNA expression of P-gp/MRP-1 was higher, whereas HDAC-2 mRNA levels were significantly lower in UA at baseline. Exposure to theophylline reduced mRNA expression of P-gp/MRP-1 (fold change: 2.57/2.15 in UA; 1.27/1.26 in CA, respectively, P < 0.0001), but the HDAC-2 mRNA expression increased (fold change: 5.56 in UA; 6.85 in CA, respectively, P < 0.0001). However, TSA treatment resulted in higher mRNA levels for P-gp/MRP-1 (fold change: 7.45/7.26 in UA; 3.34/3.29 in CA, respectively, P < 0.0001), whereas it significantly lowered expression for HDAC-2(fold change: 1.39 in UA; 2.46 in CA, respectively, P < 0.0001). Conclusion: HDAC-2 inducer theophylline has a potential to induce response against steroid resistance in severe UA. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]