Undernourished Household Contacts Are at Increased Risk of Tuberculosis (TB) Disease, but not TB Infection-a Multicenter Prospective Cohort Analysis.

Undernutrition is the leading risk factor for tuberculosis (TB) globally and in India. This multicenter prospective cohort analysis from India suggests that undernutrition is associated with increased risk of TB disease but not TB infection among household contacts of persons with TB.

Factors associated with unfavourable treatment outcomes among persons with Pulmonary Tuberculosis: a multicentric prospective cohort study from India.

In this prospective cohort of 2,006 individuals with non-MDR tuberculosis in India, 18% had unfavorable treatment outcomes (4.7% treatment failure, 2.5% recurrent infection, 4.1% death, 6.8% loss to follow-up) over a median 12-month follow-up period. Age, male sex, low education, nutritional status, and alcohol use were predictors of unfavorable outcomes.

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.

Impact of Undernutrition on Tuberculosis Treatment Outcomes in India: A Multicenter, Prospective, Cohort Analysis.

BACKGROUND: Undernutrition is the leading risk factor for tuberculosis (TB) globally. Its impact on treatment outcomes is poorly defined. METHODS: We conducted a prospective cohort analysis of adults with drug-sensitive pulmonary TB at 5 sites from 2015-2019. Using multivariable Poisson regression, we assessed associations between unfavorable outcomes and nutritional status based on body mass index (BMI) nutritional status at treatment initiation, BMI prior to TB disease, stunting, and stagnant or declining BMI after 2 months of TB treatment. Unfavorable outcome was defined as a composite of treatment failure, death, or relapse within 6 months of treatment completion. RESULTS: Severe undernutrition (BMI <16 kg/m2) at treatment initiation and severe undernutrition before the onset of TB disease were both associated with unfavorable outcomes (adjusted incidence rate ratio [aIRR], 2.05; 95% confidence interval [CI], 1.42-2.91 and aIRR, 2.20; 95% CI, 1.16-3.94, respectively). Additionally, lack of BMI increase after treatment initiation was associated with increased unfavorable outcomes (aIRR, 1.81; 95% CI, 1.27-2.61). Severe stunting (height-for-age z score <-3) was associated with unfavorable outcomes (aIRR, 1.52; 95% CI, 1.00-2.24). Severe undernutrition at treatment initiation and lack of BMI increase during treatment were associated with a 4- and 5-fold higher rate of death, respectively. CONCLUSIONS: Premorbid undernutrition, undernutrition at treatment initiation, lack of BMI increase after intensive therapy, and severe stunting are associated with unfavorable TB treatment outcomes. These data highlight the need to address this widely prevalent TB comorbidity. Nutritional assessment should be integrated into standard TB care.

Pharmacokinetics of rifampicin, isoniazid & pyrazinamide during daily & intermittent dosing: A preliminary study.

Background & objectives: The National Tuberculosis (TB) Control Programme has transitioned from thrice-weekly to daily drug treatment regimens in India. This preliminary study was conceived to compare the pharmacokinetics of rifampicin (RMP), isoniazid (INH) and pyrazinamide (PZA) in TB patients being treated with daily and thrice weekly anti-TB treatment (ATT). Methods: This prospective observational study was undertaken in 49 newly diagnosed adult TB patients receiving either daily ATT (n=22) or thrice-weekly ATT (n=27). Plasma RMP, INH and PZA were estimated by high-performance liquid chromatography. Results: The peak concentration (Cmax) of RMP was significantly higher (RMP: 8.5 µg/ml vs. 5.5 µg/ml; P=0.003) and Cmax of INH was significantly lower (INH: 4.8 µg/ml vs. 10.9 µg/ml; P<0.001) in case of daily dosing compared to thrice-weekly ATT. Cmax of drugs and doses was significantly correlated. A higher proportion of patients had subtherapeutic RMP Cmax (8.0 µg/ml) during thrice-weekly compared to daily ATT (78% vs. 36%; P=0.004). Multiple linear regression analysis showed that Cmax of RMP was significantly influenced by the dosing rhythm, pulmonary TB and Cmax of INH and PZA by the mg/kg doses. Interpretation & conclusions: RMP concentrations were higher and INH concentrations were lower during daily ATT, suggesting that INH doses may need to be increased in case of a daily regimen. Larger studies are, however, required using higher INH doses when monitoring for adverse drug reactions and treatment outcomes.

The role and diagnostic accuracy of serology for COVID-19.

BACKGROUND: The role and performance of various serological tests for the diagnosis of COVID-19 are unclear. This study aimed to evaluate the performance of seven commercially available serological assays for SARS-CoV-2 antibodies by testing COVID-19 cases and controls. METHODS: Adult patients with fever for > 5 days, admitted to a tertiary-care teaching hospital in South India, were enrolled prospectively between June and December 2020. SARS-CoV-2 RT-PCR confirmed patients were classified as cases, and patients with febrile illness with laboratory-confirmed alternative diagnosis and healthy participants were controls. All participants were tested with SCoV-2 Detect™ IgM ELISA kit and SCoV-2 Detect™ IgG ELISA kit (InBios International, Seattle, USA) (Inbios), SARS-CoV-2 Total and SARS-CoV-2 IgG (Siemens Healthcare Diagnostics Inc., Tarrytown, USA) (Siemens), Roche Elecsys® Anti-SARS-CoV-2 (Roche Diagnostics, Rotkreuz, Switzerland) (Roche), Abbott SARS-CoV-2 IgG (Abbott Diagnostics, IL, USA) (Abbott), and Liaison® SARS-CoV-2 S1/S2 IgG (DiaSorinS.p.A., Saluggia, Italy) (Liaison). The sensitivities, specificities, positive predictive values (PPV), negative predictive values (NPV), and accuracies were compared. RESULTS: There were 303 participants: 153 cases and 150 controls. ELISA detecting anti-S protein antibody was more sensitive (88.9% for IgG and 86.3% for IgM) than the CLIAs (82.4% for total antibodies and 76.5-85.6% for IgG). Among CLIAs, Roche IgG was most sensitive (85.6%) followed by Abbott (83%) and Liaison (83%). Abbot had the best PPV (88.8%) and was more specific (89.3%) than Liaison (82%) and Roche (82%). Siemens IgG was less sensitive (76.5%) than Siemens Total (82.4%). The specificity of all the serological assays was modest (75-90%). Antibody test positivity increased with the duration of illness reaching 90% after 10 days of illness. When cases were compared against pre-pandemic controls, the IgG gave excellent specificity (98-100%). For seroprevalence studies, InBios IgG had the best accuracy (90.8%) with 88.9% sensitivity and 97.6% specificity. CONCLUSION: The serological assays are important adjuncts for the diagnosis of COVID-19 in patients with persistent symptoms, especially in the second week of illness. The value of serological diagnostic tests is limited in the first week of illness and they provide additional value in seroprevalence studies. The diagnostic accuracy of the ELISA and CLIA platforms were comparable.

Prevalence of Airflow Obstruction as Measured by Spirometry, in Rural Southern Indian Adults.

Rural population-based estimates of airflow obstruction based on spirometry are unavailable from southern India. This study assessed the prevalence of spirometry-defined airflow obstruction in Vellore, Tamil Nadu.A cross sectional survey was done in nine villages, among adults aged ≥30 years, where previous cardiovascular surveys had been conducted (1994, 2011). Population proportional to size sampling was used to select 20 clusters, with sampling from all streets proportional to the number of households. One person randomly selected per household was interviewed for symptoms and risk factors. A respiratory therapist performed pre and post bronchodilator spirometry on all, following American Thoracic Society criteria. Airflow obstruction was defined as pre-bronchodilator Forced Expiratory Volume 1 s/Forced Vital Capacity (FEV1/FVC) < Lower Limit of Normal (LLN, derived from local prediction equations) and compared to other criteria.Of 1015 participants, 787 completed technically acceptable spirometry. The prevalence of airflow obstruction was 9.0% (95% CI: 5.8%-9.6%, 71). Fixed obstruction (post bronchodilator FEV1/FVC < LLN) was 4.6% (95% CI: 3.1%-6.1%, 36), and 4.1% (95% CI: 2.7%-5.5%, 32) using post bronchodilator FEV1/FVC < 70%. The GOLD criteria missed 56% (40) of those with airflow obstruction, of which 87.5% were females. Although 63.4% with airflow obstruction had moderate to severe disease, 82.2% were not on treatment and only 48.9% reported symptoms in the previous year.This study estimates prevalence of airflow obstruction based on spirometry in rural southern India. Despite significant impairment on spirometry, majority were undiagnosed, and half did not report symptoms.

Thoracoscopic pleural biopsy improves yield of Xpert MTB/RIF for diagnosis of pleural tuberculosis.

BACKGROUND AND OBJECTIVE: Extrapulmonary tuberculosis (EPTB) accounts for ~15% of all TB patients, and TB pleural effusion is the second most common site of EPTB. The diagnosis of pleural TB is challenging due to the pauci-bacillary nature of the disease. Histopathology of thoracoscopically obtained pleural biopsy provides the highest diagnostic yield. The Xpert MTB/RIF assay (Xpert) is a PCR test that can identify both Mycobacterium tuberculosis (MTB) and rifampicin resistance. Currently, there is a lack of clarity regarding the value of Xpert on pleural tissue. We report our experience of using Xpert on thoracoscopic pleural biopsy samples. METHODS: We retrospectively reviewed the records of patients who underwent thoracoscopy in our institution over a 1-year period. Relevant clinical details; indications; and results of tests on pleural tissue and fluid, including histopathology, mycobacterial cultures and Xpert, were extracted. RESULTS: Of the 156 patients who underwent thoracoscopy, 73 (47%) had TB, 66 (42%) malignancy and 17 (11%) other conditions. Histopathology was diagnostic in all the 73 TB patients (100%). The yields of the microbiological tests against histopathology on thoracoscopic biopsy sample and pleural fluid were: pleural tissue Xpert 45%, pleural tissue culture 39%, pleural fluid culture 17% and pleural fluid Xpert 14%. Pleural tissue provided higher yields than fluid in both Xpert and culture (P < 0.05). Pleural tissue Xpert provided a higher yield than culture and substantially improved yield compared with closed pleural biopsy as we previously reported. CONCLUSION: Thoracoscopic pleural biopsy results in increased sensitivity on Xpert testing.

Addition of second-line steroid sparing immunosuppressants like mycophenolate mofetil improves outcome of Immunoglobulin G4-related disease (IgG4-RD): a series from a tertiary care teaching hospital in South India.

IgG4-related disease (IgG4-RD) is a systemic fibro-inflammatory disease. This disease may be associated with elevated serum and tissue IgG4 levels. Early treatment prevents fibrosis and organ damage. We retrospectively studied the clinicopathologic correlation and outcome of treatment in IgG4-RD. This single-center retrospective study was done using electronic records of patients subjected to assay of serum IgG4 levels in our laboratory by nephelometry. There were 473 patients with suspected IgG4-RD. Of them, 41 patients fulfilled comprehensive diagnostic criteria for IgG4-RD and 432 had diseases other than IgG4-RD. Clinical and histopathological data including tissue IgG4/IgG ratio, other relevant laboratory findings as well as management data of 41 patients with IgG4-RD were analyzed. There were 29 males and 12 females with mean age of 44.1 ± 2.19 years. Thirteen patients had definite, 19 had probable and 9 had possible IgG4-RD. Male predominance, multiple organ involvement and IgG4 responder Index were significantly higher in definite IgG4-RD as compared to probable and possible IgG4-RD. Serum IgG4 level was elevated in 37 patients (90.2%). Glucocorticoids were used in 35 patients (85.4%) and second-line immunosuppressive agent in 23 patients (65.7%). Of the 21 patients on follow-up, 19 (90.7%) had clinical improvement at the first follow-up visit. Nine (90%) out of the ten patients who were assessed by IgG4 responder index, also had shown improved score with treatment. Patients with IgG4-RD in our series showed favorable responses to treatment with glucocorticoids and addition of steroid sparing immunosuppressive agents (mainly mycophenolate mofetil) helped successful tapering of steroids, while maintaining the improvement.

Prognostic Factors of Malignant Pleural Effusion among Palliative Care Outpatients: A Retrospective Study.

BACKGROUND: Malignant pleural effusion (MPE) has varied survival and indicates advanced disease. LENT prognostic score is the first validated score used for MPE. This study assessed the role of LENT among palliative care cancer patients and assessed different patient, tumor, and treatment related factors that may affect survival. METHODS: A retrospective study of advanced cancer patients with MPE, seen in palliative care outpatient clinic (2013-2015) until death, was done. LENT prognostic score could be calculated in 15 patients. Patient, tumor, and treatment related factors that affect survival were assessed. RESULTS: The study included 48 patients (70.8% female; 29.2% male) with a median age of 53 years. Lung (41.7%) was the most common primary, and adenocarcinoma (44.7%) was the most common histology. The median overall survival (OS) was 14.5 months (interquartile range [IQR]: 5.25-32.75) and median survival time (ST) was 3 months (IQR: 1-7.75). ST was significantly low with poor Eastern Cooperative Oncology Group (ECOG) performance status (P = 0.002), bilateral effusion (P < 0.001), and with no oncological treatment after MPE diagnosis (P < 0.001). OS and ST were significantly low with lung primary (P = 0.006 and 0.02, respectively). Age, gender, breathlessness, tumor histology, lung metastasis, and interventions for MPE did not significantly affect survival. The median ST in the moderate and high risk LENT groups was 6 and 3 months, respectively (P = 0.16). CONCLUSION: ECOG performance status, bilateral effusion, and no oncological treatment after diagnosis of MPE were associated with poor ST. Lung primary was associated with shorter OS and ST. Small numbers precluded any definitive conclusion on the prognostic value of LENT in our group of patients, and hence larger studies are recommended.

Lack of Utility of Thoracoscore in Evaluating Fitness for Surgery in Lung Cancer.

BACKGROUND: The thoracic surgery scoring system (Thoracoscore) is a multivariate scoring system with nine parameters used for predicting inpatient mortality after thoracic surgery. In clinical practice, the value of the thoracoscore in evaluating the fitness of individual patients for surgery is not clear. OBJECTIVE: The study objective was to evaluate the performance of thoracoscore in evaluating fitness for surgery for lung cancer and compare it with cardiopulmonary exercise test (CPEX). METHODS: We retrospectively analysed data over a 2-year period from the CPEX database of patients referred for preoperative assessment prior to surgery for lung cancer. RESULTS: Twenty-two patients who had borderline lung function impairment had CPEX to assess fitness for surgery. Fifteen (68%) were deemed fit and went on to have thoracic surgery while 7 (32%) were considered high risk and were turned down. The predicted death rate based on thoracoscore for patients who had surgery was 3.5 ± 2.8 as compared to 3.4 ± 2.0 for patients who did not have surgery (p > 0.05). The mean peak VO2 (peak oxygen uptake during CPEX) among those who had surgery was significantly higher than those who did not have surgery (14.2 mL/kg/min versus 10.1 mL/kg/min). There was no correlation of thoracoscore with lung function parameters, duration of hospital stay and peak VO2. CONCLUSIONS: Our study showed that CPEX remains a standard and useful tool for functional assessment prior to lung cancer resection. There is no correlation between thoracoscore and either CPEX or pulmonary function parameters. Thoracoscore should not be used to assess fitness for surgery.

A Rare Occurrence of Chylopericardium in a Case of Anterior Mediastinal Mass.

A middle-aged gentleman presented with dyspnea and hypotension, accompanied by an anterior mediastinal mass infiltrating the anterior chest wall and a moderate to large pericardial effusion, which upon evaluation revealed chylous fluid. Further investigation diagnosed him with right lung adenocarcinoma infiltrating the chest wall, staged at T4N3M1. The patient subsequently developed cardiac tamponade, necessitating immediate medical intervention. Management of the patient's cardiac tamponade involved pericardiocentesis via an indwelling pericardial catheter, allowing continuous drainage of the chylous fluid. Additionally, the patient was placed on a medium-chain triglyceride diet (MCTD) to reduce chyle production. These interventions resulted in significant symptomatic improvement, stabilizing the patient's hemodynamic status, and alleviating the immediate life-threatening condition. This case highlights the clinical challenges posed by rare presentations such as chylopericardium secondary to malignancy and emphasizes the importance of comprehensive diagnostic evaluation and prompt therapeutic management. The successful outcome, achieved through a combination of pericardial drainage and dietary modifications, underscores the critical role of a conservative approach in managing complex oncological cases with acute complications.

Tracheobronchopathia Osteochondroplastica - to Biopsy or not to Biopsy? A Relook at The Rare Disease.

BACKGROUND: Tracheobronchopathia osteochondroplastica (TPO) is a rare idiopathic disease involving the tracheobronchial tree. It is mostly an incidental finding with non-specific clinical manifestations. It has typical bronchoscopic, radiological features and biopsy is usually considered non-essential. The study aimed to determine whether biopsy makes a difference in the management of patients. METHODS: All patients diagnosed with TPO in our institution over 15 years (2005 to 2020) were included in this study. Their medical records, chest computed tomography (CT), and bronchoscopy reports were retrospectively reviewed, and data were analysed. All the CT images were reviewed by a senior chest radiologist. RESULTS: From the 20,000 bronchoscopies and 260,000 CT thorax images obtained, 28 cases were diagnosed as TPO based on either bronchoscopy or radiology or both. Among the 19 cases diagnosed through bronchoscopy, 16 underwent a biopsy. In addition to TPO features, biopsy showed additional diagnoses in 6 cases. In 9 cases, TPO was not initially diagnosed by CT but by bronchoscopy. In 8 patients, TPO was diagnosed incidentally on CT performed for other reasons. On follow-up with the treatment of underlying/co-existing concomitant aetiologies, clinical improvement was noted in all patients. None of them progressed to respiratory failure or airway obstruction until the last follow-up. CONCLUSION: Among patients who underwent bronchoscopic biopsy of TPO lesions, 38% had biopsy results showing an alternative aetiology, which led to changes in the treatment plan for all these patients. Hence, a bronchoscopic biopsy of TPO lesions should be performed to rule out other aetiologies.

Impact of post-COVID-19 lung damage on pulmonary function, exercise tolerance and quality of life in Indian subjects.

After recovery from COVID-19, there is data to suggest potential long-term pulmonary sequelae and associated impairment of functional capacity. This cross-sectional study was designed to assess the impact on respiratory function in a cohort of Indian subjects. Subjects who had recovered from COVID-19 were recruited. Clinical symptoms, pulmonary function test results, 6-minute walk test (6MWT) results, St George's Respiratory questionnaire (SGRQ) and chest radiographs were obtained. Information on the COVID-19 illness during hospitalization, baseline laboratory biomarkers and the disease severity categories as outlined by WHO (asymptomatic, mild, moderate, severe and critical), were retrieved from the hospital records. The 'COVID pneumonia'(WHO category moderate, severe & critical) group was compared with the 'Mild COVID' (WHO category mild) group and likewise, the WHO category moderate and the WHO category severe/critical groups were compared. In 207 subjects, whose mean age was 48.7 years were assessed after an average of 63 days from onset of symptom, 35% had TLC< 80% (restrictive defect), 8.3% had FEV1/FVC<70% (obstructive defect) and 44.4% had diminished DLCO<80% (diffusing capacity). The 'COVID-19 pneumonia' group when compared to the 'mild COVID-19' group, had lower FVC% (77.85 VS 88.18; P = 0.001), TLC% (79.48 VS 87.91; P = 0.0002), DLCO% (75.30 VS 89.20; P<0.0001) and DLCO/VA% (105.6 VS 111.8; P = 0.032), decreased minimum oxygen saturation (94.89 VS 97.73; P<0.0001) and more subjects had a drop in saturation of ≥ 4% (21.69% VS 4.84%; P = 0.001) during the 6MWT, and a greater mean total SGRQ score (29.2 VS 11.0; P<0.0001). To our knowledge, this is the first such report on Indian subjects. We have shown that post-COVID-19 lung damage leads to significant impairment of lung function, quality of life and effort tolerance.

Tuberculin test using Indian indigenous purified-protein derivative (PPD) shows only moderate agreement with international standard PPD.

Background: In India, the prevalence of Latent TB infection (LTBI) is estimated to be around 40%. Various formulations of PPD(Purified protein derivative) are available, for diagnosis of LTBI, which may give variable responses. The commercially available PPD in India is by Arkray Healthcare (TST-Arkray). It is unclear if this product may have a similar sensitivity compared to other internationally accepted tuberculins (TST-Tubersol). Objectives: To assess the performance of the two TSTs compared to Quantiferon-Gold Plus (QFT-Plus). Methodology: A blood sample was collected for the QFT-Plus test. Both the TSTs were placed in the right and the left volar aspect of the forearms and 48 hrs later, the subjects came back to the study site for reading. Results: Among the 512 participants who were recruited, 326 subjects were healthcare professionals and 186 subjects were household contacts of patients with tuberculosis. They were tested with both TST-Tubersol and TST-Arkray, 139(27 %) participants tested positive for TST-Tubersol (≥10 mm), whereas 203 participants (40.1 %)tested positive for TST-Arkray. There was moderate agreement between the two tests with k = 0.58. Also, there was only poor agreement between both the TSTs with QFT Plus(kappa = 0.19 for Tubersol and 0.17 for Arkray). With QFT-Plus as gold standard, the sensitivity, specificity, PPV and NPV of TST-Tubersol, ast an induration cut-off of 10 mm was 46.8 %,76.3 %,31.8 % and 85.8 %. respectively and TST- Arkray; 60.6 %, 64 %, 28.5 % and 87.2 % respectively. Conclusion: The Indian TST (Arkray Diagnostics) has shown moderate agreement with the internationally accepted Tubersol. Additionally, there was poor agreement between the TSTs and QFT plus test.

Multi-centric evaluation of Truenat MTB and MTB-RIF Dx assays for diagnosis of extrapulmonary tuberculosis.

Extra-pulmonary TB (EPTB) is difficult to diagnose due to paucibacillary nature of disease. Current study evaluated accuracy of Truenat MTB and MTB-Rif Dx (TN), for detection of Mycobacterium tuberculosis and resistance to rifampicin. Samples were collected from 2103 treatment naive adults with presumptive EPTB, and tested by smear microscopy, liquid culture (LC) (MGIT-960) and GeneXpert MTB/RIF (GX) (Microbiological Reference Standards, MRS). TN results were compared to MRS and Composite Reference Standards (CRS, Microbiology, histopathology, radiology, clinical features prompting decision to treat, response to treatment). CRS grouped patients into 551 confirmed, 1096 unconfirmed, and 409 as unlikely TB. TN sensitivity and specificity was 73.7% and 90.4% against GX. Against LC, Overall sensitivity of GX was 67.6%, while that of TN was 62.3%. Highest sensitivity by TN was observed in pus samples (89%) and highest specificity (92%) in CSF samples, similar to GX. TN sensitivity was better in fluid and biopsy samples and slightly inferior for lymph node aspirates compared to GX. TN sensitivity for RIF resistance detection was slightly superior to GX. TN and GX results were further compared to Clinical Reference Standards. TN detected 170 TB patients initiated on treatment missed by GX, while GX detected 113 such patients missed by TN. Of 124 samples with RIF resistance discordance between GX and TN, GX reported 103/124 as sensitive, 3/124 as indeterminate and 18 as resistant (13/18 samples had low/very low DNA load) while TN reported RIF resistance indeterminate in 103/111 low/very low DNA load samples. Due to paucibacillary nature of EPTB samples, culture yield was poor and phenotypic drug susceptibility testing failed to resolve the discordance. The study establishes TN at par with GX and can be utilized for quick and accurate diagnosis of EPTB.

An independent, multi-country head-to-head accuracy comparison of automated chest x-ray algorithms for the triage of pulmonary tuberculosis.

Background: Computer-aided detection (CAD) algorithms for automated chest X-ray (CXR) reading have been endorsed by the World Health Organization for tuberculosis (TB) triage, but independent, multi-country assessment and comparison of current products are needed to guide implementation. Methods: We conducted a head-to-head evaluation of five CAD algorithms for TB triage across seven countries. We included CXRs from adults who presented to outpatient facilities with at least two weeks of cough in India, Madagascar, the Philippines, South Africa, Tanzania, Uganda, and Vietnam. The participants completed a standard evaluation for pulmonary TB, including sputum collection for Xpert MTB/RIF Ultra and culture. Against a microbiological reference standard, we calculated and compared the accuracy overall, by country and key groups for five CAD algorithms: CAD4TB (Delft Imaging), INSIGHT CXR (Lunit), DrAid (Vinbrain), Genki (Deeptek), and qXR (qure.AI). We determined the area under the ROC curve (AUC) and if any CAD product could achieve the minimum target accuracy for a TB triage test (≥90% sensitivity and ≥70% specificity). We then applied country- and population-specific thresholds and recalculated accuracy to assess any improvement in performance. Results: Of 3,927 individuals included, the median age was 41 years (IQR 29-54), 12.9% were people living with HIV (PLWH), 8.2% living with diabetes, and 21.2% had a prior history of TB. The overall AUC ranged from 0.774-0.819, and specificity ranged from 64.8-73.8% at 90% sensitivity. CAD4TB had the highest overall accuracy (73.8% specific, 95% CI 72.2-75.4, at 90% sensitivity), although qXR and INSIGHT CXR also achieved the target 70% specificity. There was heterogeneity in accuracy by country, and females and PLWH had lower sensitivity while males and people with a history of TB had lower specificity. The performance remained stable regardless of diabetes status. When country- and population-specific thresholds were applied, at least one CAD product could achieve or approach the target accuracy for each country and sub-group, except for PLWH and those with a history of TB. Conclusions: Multiple CAD algorithms can achieve or exceed the minimum target accuracy for a TB triage test, with improvement when using setting- or population-specific thresholds. Further efforts are needed to integrate CAD into routine TB case detection programs in high-burden communities.

Head-to-head comparison of diagnostic accuracy of TB screening tests: Chest-X-ray, Xpert TB host response, and C-reactive protein.

Background: Accessible, accurate screening tests are necessary to advance tuberculosis (TB) case finding and early detection in high-burden countries. We compared the diagnostic accuracy of available TB triage tests. Methods: We prospectively screened consecutive adults with ≥2 weeks of cough presenting to primary health centers in the Philippines, Vietnam, South Africa, Uganda, and India. All participants received the index tests: chest-X-ray (CXR), venous or capillary Cepheid Xpert TB Host Response (HR) testing, and point-of-care C-reactive protein (CRP) testing (Boditech iChroma II). CXR images were processed using computer-aided detection (CAD) algorithms. We assessed diagnostic accuracy against a microbiologic reference standard (sputum Xpert Ultra, culture). Optimal cut-points were chosen to achieve sensitivity ≥90% and maximize specificity. Two-test screening algorithms were considered, using two approaches: 1) sequential negative serial screening in which the second screening test is conducted only if the first is negative and positive is defined as positive on either test and 2) sequential positive serial screening, in which the second screening test is conducted only if the first is positive and positive is defined as positive on both tests. Results: Between July 2021 and August 2022, 1,392 participants with presumptive TB had valid results on index tests and the reference standard, and 303 (22%) had confirmed TB. In head-to-head comparisons, CAD4TB v7 showed the highest specificity when using a cut-point that achieves 90% sensitivity (70.3% vs. 65.1% for Xpert HR, difference 95% CI 1.6 to 8.9; 49.7% for CRP, difference 95% CI 17.0 to 24.3). Among the possible two-test screening algorithms, three met WHO target product profile (TPP) minimum accuracy thresholds and had higher accuracy than any test alone. At 90% sensitivity, the specificity was 79.6% for Xpert HR-CAD4TB [sequential negative], 75.9% for CRP-CAD4TB [sequential negative], and 73.7% for Xpert HR-CAD4TB [sequential positive]. Conclusions: CAD4TB achieves TPP targets and outperforms Xpert HR and CRP. Combining screening tests further increased accuracy. Cost and feasibility of two-test screening algorithms should be explored. Registration: NCT04923958.

Biomarkers of coagulation, endothelial, platelet function, and fibrinolysis in patients with COVID-19: a prospective study.

Prospective and sequential evaluation of homeostatic changes leading to thrombosis across COVID 19 disease severity spectrum are limited. In this prospective observational study, haemostasis was evaluated in patients with mild, moderate-severe, and critical COVID-19 infection. Markers of endothelial activation [Soluble thrombomodulin (sTM), von Willebrand Factor (VWF)], platelet activation [Soluble P-selectin, beta-thromboglobulin (BTG)] and global haemostasis [Rotational thromboelastometry (ROTEM)] were evaluated on days 1 and 5 after admission. The study cohort comprised of 100 adult patients (mild = 20, moderate-severe = 22, critical = 58). Sixty-five patients received anticoagulation for 10 (7-14) days. Thrombotic events were seen in 9 patients. In-hospital mortality was 21%. Endothelial activation markers were elevated at baseline in all subgroups, with levels in moderate-severe (sTM = 4.92 ng/ml, VWF = 295 U/dl) [reference-ranges: sTM = 2.26-4.55 ng/ml; Soluble P-selectin = 13.5-31.5 ng/ml; BTG = 0.034-1.99 ng/ml] and critical patients (sTM = 6.07 ng/ml, VWF = 294 U/dl) being significantly higher than in the mild group (sTM = 4.18 ng/ml, VWF = 206 U/dl). In contrast, platelet activation markers were elevated only in critically ill patients at baseline (Soluble P-selectin = 37.3 ng/ml, BTG = 2.51 ng/ml). The critical group had significantly lower fibrinolysis on days 1 and 5 when compared with the moderate-severe arm. COVID-19 infection was associated with graded endothelial activation and lower fibrinolysis that correlated with illness severity.

Pleural effusion guidelines from ICS and NCCP Section 1: Basic principles, laboratory tests and pleural procedures.

Pleural effusion is a common problem in our country, and most of these patients need invasive tests as they can't be evaluated by blood tests alone. The simplest of them is diagnostic pleural aspiration, and diagnostic techniques such as medical thoracoscopy are being performed more frequently than ever before. However, most physicians in India treat pleural effusion empirically, leading to delays in diagnosis, misdiagnosis and complications from wrong treatments. This situation must change, and the adoption of evidence-based protocols is urgently needed. Furthermore, the spectrum of pleural disease in India is different from that in the West, and yet Western guidelines and algorithms are used by Indian physicians. Therefore, India-specific consensus guidelines are needed. To fulfil this need, the Indian Chest Society and the National College of Chest Physicians; the premier societies for pulmonary physicians came together to create this National guideline. This document aims to provide evidence based recommendations on basic principles, initial assessment, diagnostic modalities and management of pleural effusions.