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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]

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. [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: 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: 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 × 103 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. [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]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]