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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).)

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.

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

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.)

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.

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.)

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.

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

Background: Bronchoscopic lung cryobiopsy (BLC) is a novel technique for obtaining lung tissue for the diagnosis of diffuse parenchymal lung diseases. The procedure is performed using several different variations of technique, resulting in an inconsistent diagnostic yield and a variable risk of complications. There is an unmet need for standardization of the technical aspects of BLC., Methodology: This is a position statement framed by a group comprising experts from the fields of pulmonary medicine, thoracic surgery, pathology, and radiology under the aegis of the Indian Association for Bronchology. Sixteen questions on various technical aspects of BLC were framed. A literature search was conducted using PubMed and EMBASE databases. The expert group discussed the available evidence relevant to each question through e-mail and a face-to-face meeting, and arrived at a consensus., Results: The experts agreed that patients should be carefully selected for BLC after weighing the risks and benefits of the procedure. Where appropriate, consideration should be given to perform alternate procedures such as conventional transbronchial biopsy or subject the patient directly to a surgical lung biopsy. The procedure is best performed after placement of an artificial airway under sedation/general anesthesia. Fluoroscopic guidance and occlusion balloon should be utilized for positioning the cryoprobe to reduce the risk of pneumothorax and bleeding, respectively. At least four tissue specimens (with at least two of adequate size, i.e., ≥5 mm) should be obtained during the procedure from different lobes or different segments of a lobe. The histopathological findings of BLC should be interpreted by an experienced pulmonary pathologist. The final diagnosis should be made after a multidisciplinary discussion. Finally, there is a need for structured training for performing BLC., Conclusion: This position statement is an attempt to provide practical recommendations for the performance of BLC in DPLDs., Competing Interests: None

Tracheobronchopathia osteochondroplastica is an idiopathic non-malignant disease of large airways featured by submucosal cartilaginous to osseous nodules overlying the cartilaginous rings, which may be focal or diffuse. Clinical presentation varies from asymptomatic to symptoms like breathlessness, recurrent chest infections, cough and hemoptysis. Due to the lack of awareness of this disease, it remains an under recognized entity. We are describing the computed tomography and bronchoscopic findings of two recently diagnosed cases at our institute. The purpose of this report is to familiarize radiologists with imaging appearance of this condition, with the goal of increasing clinical suspicion of this uncommon condition.

Maternal hypothyroidism affects postnatal lung structure. High prevalence of hypothyroxinemia (low T4, normal T3) in iodine-deficient pregnant women and associated risk for neuropsychological development along with high infant/neonatal mortality ascribed to respiratory distress prompted us to study the effects of maternal hypothyroxinemia on postnatal lung development. Female Sprague Dawley rats were given a low-iodine diet (LID) with 1% KClO(4) in drinking water for 10 days, to minimize thyroid hormone differences. Half of these rats were continued on iodine-deficient diet; ID (LID with 0.005% KClO(4)) for 3 mo, whereas the rest were switched to an iodine-sufficient diet; IS [LID + potassium iodide (10 μg iodine/20 g of diet + normal drinking water)]. Pups born to ID mothers were compared with age-matched pups from IS mothers at postnatal days 8 (P8) and 16 (P16) (n = 6-8/group). ID pups had normal circulating T3 but significantly low T4 levels (P < 0.05) and concomitantly approximately sixfold higher thyroid hormone receptor-β mRNA in alveolar epithelium. Lung histology revealed larger and irregularly shaped alveoli in ID pups relative to controls. Lung function was assessed at P16 using a double-chambered plethysmograph and observed reduced tidal volume, peak inspiratory and expiratory flow, and dynamic lung compliance in ID pups compared with IS pups. Significant lowering of surfactant protein (SP)-B and SP-C mRNA and protein found in ID pups at P16. ID pups had 16-fold lower matrix metalloproteinase-9 mRNA levels in their alveolar epithelium. In addition, mRNA levels of thyroid transcription factor-1 and SP-D were significantly higher (3-fold) compared with IS pups. At P16, significantly lower levels of SP-B and SP-C found in ID pups may be responsible for immature lung development and reduced lung compliance. Our data suggest that maternal hypothyroxinemia may result in the development of immature lungs that, through respiratory distress, could contribute to the observed high infant mortality in ID neonates.

Initially described by a group of Japanese clinicians and pulmonary pathologists to distinguish it from other chronic obstructive lung diseases, diffuse panbronchiolitis (DPB) is an uncommon disorder which has been reported largely from the eastern world. It is imperative to recognise this condition because of its potentially treatable nature. Recently, long-term macrolide therapy has revolutionised its management. Herein, we describe a 65-year-old male who was being managed as a case of chronic bronchitis before this diagnosis was suspected and proved.