Search

Background and objective: There is a need for simple functional test to assess treatment response in chronic pulmonary aspergillosis (CPA) in resource-constrained settings. The one-minute-sit-to-stand test (1-min-STS) is one such test. However, the minimal important difference (MID) for 1-min-STS in subjects with CPA remains unknown. Herein, we estimate the MID for 1-min-STS for CPA subjects. Materials and Methods: We retrospectively reviewed the clinical details of CPA subjects treated with oral azoles for 6 months. We included only subjects who completed the 1-min-STS test at baseline and 6 months. We used the change in VAS (visual analogue scale, for overall improvement) as an external anchor. We used the anchor and the distribution (standard deviation-based) methods to determine the MID estimates. We used the anchor-based method only if there was correlation of 0.3 with the 1-min-STS test. Results: One hundred-eight subjects completed the 1-min-STS test at baseline and 6 months. We did not find significant correlation between the change in VAS for overall improvement (r² = 0.024, P value = 0.809) and the 1-min-STS test. The MID for the 1-min-STS test was 2 repetitions (range, 1.5--2.8 repetitions). Conclusion: The MID for the 1-min-STS test in subjects with CPA was 2 repetitions. Future studies using a global rating of change scale as an anchor must confirm our findings. [ABSTRACT FROM AUTHOR]

The article focuses on assessing the prevalence of allergic sensitization to Aspergillus fumigatus (AS) in chronic obstructive pulmonary disease (COPD) patients, comparing smokers and non-smokers. It explores the association between AS and factors like tobacco smoking, biomass fuel exposure, and the prevalence of allergic bronchopulmonary aspergillosis (ABPA), particularly in those who smoke bidis or cigarettes.

Yes: 65No: 974 REFERENCES 1 Sehgal IS, Dhooria S, Prasad KT, Muthu V, Aggarwal AN, Agarwal R. Barrier enclosure device during patient preparation for flexible bronchoscopy. Sir, We have previously described a barrier enclosure device use to limit aerosol dispersion during high aerosol-generating procedures such as flexible bronchoscopy and endotracheal intubation to protect health-care workers.[[1]],[[2]] While using the barrier enclosure device, one may occasionally encounter difficulty in sampling lesions located either distally or in the upper lobes posterior segment. [Extracted from the article]

This document is a research letter published in the journal Lung India. It describes a very rare case of anomalous systemic arterial supply to the lung without sequestration. The patient presented with abnormal vessels extending from the celiac trunk to the inferior vena cava, supplying the lung. This condition is a congenital abnormality that is usually associated with pulmonary sequestration, but in this case, the sequestration was absent. The document provides a brief overview of bronchopulmonary sequestration and discusses the rarity of systemic arterial supply to the lung without sequestration. [Extracted from the article]

Background: Tracheobronchial mucormycosis is a fatal opportunistic infection that mainly causes airway stenosis and is difficult to manage clinically. Case presentation: We report a case of severe tracheal stenosis caused by tracheobronchial mucormycosis in a 37-year-old female with a history of hyperthyroidism. She developed agranulopenia after oral methimazole administration and subsequently experienced asthma with dyspnea. Bronchoscopy, sputum culture, colony mass spectrometry, and microscopic cotton orchid staining confirmed tracheobronchial mucormycosis. The patient received venous-venous extracorporeal membrane oxygenation (VV-ECMO) and prolonged intratracheal instillation of amphotericin B (AmBD), combined with amphotericin B liposome (L-AmB) and isavuconazole intravenous infusion, ultimately resulting in successful treatment. Conclusion: VV-ECMO combined with prolonged intratracheal instillation of AmBD is an effective method for the treatment of tracheobronchial mucormycosis. [ABSTRACT FROM AUTHOR]

A severe and progressive interstitial lung disease (ILD) known as idiopathic pulmonary fibrosis (IPF) has an unknown etiology with poorly defined mechanisms of development. Among the currently prescribed pharmacological interventions for IPF, nintedanib demonstrates the ability to decelerate the deterioration of lung function and yield positive clinical outcomes. Multiple randomized placebo-controlled trials have confirmed the efficacy and acceptable safety profile of nintedanib. Real-world evidence studies also support the use of nintedanib in IPF, being an efficient and well-tolerated treatment option. It has the potential to stabilize the disease progression in patients with ILD. Patients with IPF frequently have comorbidities like diabetes and hypertension, which can exacerbate the course of disease, reduce quality of life, and decrease treatment adherence. For well-informed decision-making, it is important for healthcare professionals to recognize the position of nintedanib therapy in IPF with comorbidities. The gastrointestinal adverse effects, notably diarrhea, dominate the nintedanib safety profile. These can be effectively controlled by closely monitoring side effects, administering anti-diarrheal and anti-emetic drugs, reducing the nintedanib dose, and discontinuing it in case of severe symptoms with an option to reintroduce the treatment after side effects subside. Symptomatic interventions and monitoring of liver enzymes may reduce the occurrence of permanent treatment discontinuations. [ABSTRACT FROM AUTHOR]

Immunomodulating agents interact with the immune system and alter the outcome of specific immune processes. As our understanding of the immune system continues to evolve, there is a growing effort to identify agents with immunomodulating applications to use therapeutically to treat various diseases. Mycobacterium w (Mw), a heat-killed mycobacterium, is an atypical mycobacterial species that possesses strong immunomodulatory properties. Mw was initially evaluated as an immune-therapeutic against leprosy, but since then Mw has generated a lot of interest and been studied for therapeutic applications across a host of diseases, such as pulmonary tuberculosis, tuberculous pericarditis, sepsis, lung cancer, and more. This article summarizes a large body of work published in the past five decades, describing various aspects of Mw and its potential for further therapeutic development. [ABSTRACT FROM AUTHOR]

Background: Mucormycosis is a highly lethal opportunistic fungal disease caused by ubiquitous molds of the order Mucorales, with Rhizopus, Lichtheimia and Mucor being the most common genera. This rare disease primarily affects immunocompromised patients, with presentations ranging from rhino-orbito-cerebral infections to disseminated mucormycosis with angioinvasion, leading to thrombosis and tissue infarction. Gastrointestinal mucormycosis is the least common clinical presentation and is believed to be secondary to spore ingestion. It can involve multiple components of the gastrointestinal tract, such as the stomach, liver, ileum, and colon, with nonspecific manifestations, including pain, nausea, vomiting, and abdominal distension. The initial clinical presentation may even manifest as gastrointestinal bleeding due to gastric ulceration or intestinal perforation. Case presentation: Here we present the case of a 48-year-old male patient with a 9-year history of human immunodeficiency virus (HIV) infection who was hospitalized in the context of febrile neutropenia and whose acute respiratory infection was documented; therefore, antibiotic treatment was initiated. However, due to persistent febrile peaks and peripheral blood showing documentation of multilineage cytopenias, a bone marrow biopsy was performed, compatible with presenting features of marrow myelodysplasia. During hospitalization, the patient presented left flank abdominal pain, and an abdominal computed tomography (CT) scan revealed signs of intussusception of a small bowel loop at the distal jejunum level, leading to intestinal obstruction with ischemic progression, requiring ileectomy (60 cm). Histopathological analysis of the resected intestine revealed severe transmural ischemic changes associated with venous thrombosis due to fungal structures, with histochemical studies demonstrating the presence of zygomycete (Mucor) fungal structures, leading to the initiation of treatment with amphotericin B. However, despite treatment, the patient experienced progressive clinical deterioration with persistent fever and ventilatory failure, with follow-up tests showing absolute neutropenia and blood cultures positive for yeast, leading to death 52 days after admission. Conclusions: The diagnosis of intestinal mucormycosis may be delayed due to the lack of specificity of the signs and symptoms. Pathologists as well as histopathological studies are essential for timely treatment. [ABSTRACT FROM AUTHOR]

Background: Various types of needles are available to perform endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA). A relatively new needle for EBUS-TBNA, the Acquire Fine Needle Biopsy (FNB) device, has recently become available. Methods: Consecutive subjects with lymphadenopathy >1 cm undergoing EBUS-TBNA were randomized to the Acquire 22-G EBUS-FNB needle and the standard 22-G EBUS-TBNA needle groups. Results: A total of 86 subjects were randomized (43 in each group). The diagnostic yield of EBUS-TBNA was similar between the two groups: (36/43) 83.7% in the 22-G EBUS-FNB group and (34/43) 79.1% in the standard 22-G EBUS group (p = 0.58). The sampling adequacy, stations sampled, number of stations sampled, number of needle passes, and mean duration of the procedure between the two groups were also similar. Visible tissue clot core was obtained in a significantly greater proportion of subjects in the 22-G EBUS-FNB group (93.0% vs 46.5%, p < 0.001). Visibly bloody samples were more frequent in the 22-G EBUS-FNB group (74.4% vs 51.2%, p = 0.03). There was no difference in the complication rates between the two groups (p = 0.15). Conclusion: We did not observe a difference in the diagnostic yield of the Acquire 22-G EBUS-FNB needle compared with the standard 22-G EBUS needle. Clinical trial registration: Clinical Trial Registry of India (CTRI) (CTRI/2021/08/035589). [ABSTRACT FROM AUTHOR]

The European Respiratory Society (ERS) and the British Thoracic Society (BTS) have recently published their statements on the treatment of sarcoidosis. There are five key questions in sarcoidosis treatment that need to be addressed: when to treat, how to initiate treatment, how long to treat, when and how to change treatment, and how to treat relapses. Herein, we describe the principles and protocols to answer these questions based on the ERS and BTS statements and other expert reviews. Pulmonary or extrapulmonary sarcoidosis should be treated with anti-inflammatory therapy if it significantly impairs the quality of life (QoL), causes significant organ dysfunction, or threatens to cause organ damage, disability, or death. If treatment is initiated for improving the QoL alone, low-dose (10 mg/day) prednisone is a good initial treatment that can be tapered and stopped over 3 months. Disease that causes significant organ dysfunction needs to be treated with medium-dose glucocorticoids (initial daily dose, 20 mg of prednisone equivalent) tapered over a minimum duration of 6 months. Worsening of disease while tapering treatment indicates that longer (9-24 months) treatment may be necessary. If a daily prednisone dose of >10 mg is required for >6 months to maintain remission, it is best to use a second-line drug such as methotrexate or azathioprine. Anti-tumor necrosis factor agents, such as infliximab or adalimumab, may be used to treat inflammatory disease that persists on combination treatment with glucocorticoids and a second-line agent. [ABSTRACT FROM AUTHOR]

In the present review, we focused on recent translational and clinical discoveries in asthma immunology, facilitating phenotyping and stratified or personalized interventions for patients with this condition. The immune processes behind chronic inflammation in asthma exhibit marked heterogeneity, with diverse phenotypes defining discernible features and endotypes illuminating the underlying molecular mechanisms. In particular, two primary endotypes of asthma have been identified: "type 2-high," characterized by increased eosinophil levels in the airways and sputum of patients, and "type 2-low," distinguished by increased neutrophils or a pauci-granulocytic profile. Our review encompasses significant advances in both innate and adaptive immunities, with emphasis on the key cellular and molecular mediators, and delves into innovative biological and targeted therapies for all the asthma endotypes. Recognizing that the immunopathology of asthma is dynamic and continuous, exhibiting spatial and temporal variabilities, is the central theme of this review. This complexity is underscored through the innumerable interactions involved, rather than being driven by a single predominant factor. Integrated efforts to improve our understanding of the pathophysiological characteristics of asthma indicate a trend toward an approach based on disease biology, encompassing the combined examination of the clinical, cellular, and molecular dimensions of the disease to more accurately correlate clinical traits with specific disease mechanisms. [ABSTRACT FROM AUTHOR]

Background: There is substantial evidence indicating that cytokines play a role in the immune defense against tuberculosis. This study aims to evaluate the levels of various cytokines in pleural effusion to ditinguish between tuberculosis pleurisy and malignant pleurisy. Methods: A total of 82 participants with pleural effusion were included in the training cohort, and 76 participants were included in the validation cohort. The individuals were divided into tuberculosis and malignant pleurisy groups. The concentrations of interleukin-1β (IL-1β), IL-4, IL-6, IL-10, IL-17 A, IL-17 F, IL-21, IL-22, IL-25, IL-31, IL-33, interferon-γ (IFN-γ), soluble CD40 ligand (sCD40L) and tumor necrosis factor-α (TNF-α) in pleural effusion were measured using a multiplex cytokine assay. The threshold values were calculated according to the receiver operating characteristic (ROC) curve analysis to aid in diagnosing tuberculosis pleurisy. Furthermore, the combined measure was validated in the validation cohort. Results: The levels of all 14 cytokines in pleural effusion were significantly higher in participants with tuberculosis compared to those with malignant pleurisy (all P < 0.05). The area under the curve (AUC) was ≥ 0.920 for the IL-22, sCD40L, IFN-γ, TNF-α and IL-31, which were significantly increased in tuberculous pleural effusion (TPE) compared to MPE in the training cohort. Threshold values of 95.80 pg/mL for IFN-γ, 41.80 pg/mL for IL-31, and 18.87 pg/mL for IL-22 provided ≥ 90% sensitivity and specificity in distinguishing between tuberculosis pleurisy and malignant pleurisy in the training cohort. Among these, IL-22 combined with sCD40L showed the best sensitivity and specificity (94.0% and 96.9%) for diagnosing tuberculosis pleurisy, and this finding was validated in the validation cohort. Conclusion: We demonstrated that the levels of IL-1β, IL-4, IL-6, IL-10, IL-17 A, IL-17 F, IL-21, IL-22, IL-25, IL-31, IL-33, IFN-γ, sCD40L and TNF-α in pleural effusion had significant difference between tuberculosis pleurisy and malignant pleurisy. Specifically, IL-22 ≥ 18.87 pg/mL and sCD40L ≥ 53.08 pg/mL can be clinically utilized as an efficient diagnostic strategy for distinguishing tuberculosis pleurisy from malignant pleurisy. [ABSTRACT FROM AUTHOR]

Introduction: The diagnosis of tuberculous (TB) pleurisy remains difficult because of its paucibacillary character. Several authors have studied the usefulness of interferon gamma release assays in the early diagnosis of TB pleurisy, whereas these tests are designed for the detection of latent TB infection. Our objective is to study the performance and clinical relevance of QuantiFERON TB Gold in Tube (QFT-GIT) in the diagnosis of TB pleurisy in Algeria. Patients and methods: QFT-GIT was tested in vitro in serum and pleural fluid on a prospective recruitment of 158 immunocompetent patients with pleural effusion. Results: Of the 158 cases of pleurisy identified, 84 (53.84%) were TB, diagnosed and proven by conventional methods, and 72 (46.15%) were non-TB, of whom 67 (93%) were confirmed of neoplastic origin, five (7%) secondary to a systemic disease and two of nonspecific inflammatory origin. Our results showed a high pleural sensitivity of QFT-GIT (97.62%) compared to serum sensitivity (80.95%). In contrast, serum specificity (83.78%) was higher than pleural specificity (72.97%). When we used the optimal values from the receiver operation characteristics curve analysis, the area under the curve of interferon-gamma produced by the QFT-GIT test was significantly higher in the pleural fluid than in the blood. Area under the curve of TB antigen interferon-gamma response was 92, 18 [95% confidence interval (CI)=87.56–96.79], nil tube was 95.71% (95% CI=92.43–99), and mitogen tube was 65.34 (95% CI=57.71–72.98). Conclusion: QFT-GIT in pleural fluid appears in our study as a useful test for the diagnosis of TB pleurisy, but its diagnostic accuracy needs to be validated in further large-scale research. [ABSTRACT FROM AUTHOR]

Persistent air leak may complicate malignant disease of the thorax, causing significant morbidity and mortality. A 51‐year‐old male with a 30‐pack‐year history of smoking was diagnosed with metastatic esophageal carcinoma with invasion into the right upper lobe of the lung. He developed a large right hydropneumothorax complicated by empyema leading to persistent air leak despite the insertion of two chest drains. Computed Tomography imaging with 3‐dimensional reconstruction showed severe tracheal compression from the enlarging esophageal tumour as well as bronchopleural fistulas in the right upper lobe. Rigid bronchoscopy with metallic tracheal stenting was performed. This was followed by localization and quantification of air leak with an endobronchial collateral ventilation assessment system and a digital chest drain to guide endobronchial valve placement, in a single operative procedure. This novel combination of interventional bronchoscopy techniques enabled successful transition to an ambulatory chest drain and subsequent hospital discharge. [ABSTRACT FROM AUTHOR]

Lack of the established noninvasive diagnostic biomarkers causes delay in diagnosis of lung cancer (LC). The aim of this study was to explore the association between inflammatory and cancer‐associated plasma proteins and LC and thereby discover potential biomarkers. Patients referred for suspected LC and later diagnosed with primary LC, other cancers, or no cancer (NC) were included in this study. Demographic information and plasma samples were collected, and diagnostic information was later retrieved from medical records. Relative quantification of 92 plasma proteins was carried out using the Olink Immuno‐Onc‐I panel. Association between expression levels of panel of proteins with different diagnoses was assessed using generalized linear model (GLM) with the binomial family and a logit‐link function, considering confounder effects of age, gender, smoking, and pulmonary diseases. The analysis showed that the combination of five plasma proteins (CD83, GZMA, GZMB, CD8A, and MMP12) has higher diagnostic performance for primary LC in both early and advanced stages compared with NC. This panel demonstrated lower diagnostic performance for other cancer types. Moreover, inclusion of four proteins (GAL9, PDCD1, CD4, and HO1) to the aforementioned panel significantly increased the diagnostic performance for primary LC in advanced stage as well as for other cancers. Consequently, the collective expression profiles of select plasma proteins, especially when analyzed in conjunction, might have the potential to distinguish individuals with LC from NC. This suggests their utility as predictive biomarkers for identification of LC patients. The synergistic application of these proteins as biomarkers could pave the way for the development of diagnostic tools for early‐stage LC detection. [ABSTRACT FROM AUTHOR]

Background Tuberculous pleural effusion (TPE) is the most common form of extrapulmonary tuberculosis in many settings. The diagnostic performance of the frontline polymerase chain reaction–based GeneXpert MTB/RIF Ultra (Xpert Ultra) remains suboptimal (sensitivity of ∼30%), but data are limited. Improved diagnostic approaches are urgently needed to detect extrapulmonary tuberculosis (EPTB) in tuberculosis (TB)-endemic settings. Methods This multicenter, prospective cohort study evaluated the diagnostic performance of a rapid (same-day) interferon gamma rapid immunosuspension assay (IRISA-TB) in patients with presumed TPE from South Africa and India. Participants underwent pleural biopsy, and testing with other available same-day diagnostic assays (adenosine deaminase [ADA], Xpert Ultra, and IRISA-TB) was concurrently undertaken. The reference standard for TB was microbiological and/or histopathological confirmation using pleural fluid and/or pleural biopsy samples. Results A total of 217 participants with presumed TPE were recruited (106 from South Africa, 111 from India). The sensitivity of IRISA-TB (cut-point 20.5 pg/mL) was significantly better than that of Xpert Ultra (81.8% [70.4–90.2] vs 32.9% [22.1–45.1]; P <.001) and ADA at the 40 IU/mL cut-point used in India (81.8% [70.4–90.2] vs 53.8% [41.0–66.3]; P =.002). Compared with ADA at the 30 IU/mL cut-point used in South Africa, IRISA-TB had a higher specificity (96.6% [90.3–99.3] vs 87.1% [78.6–93.2]) and a higher positive predictive value (94.7% [85.5–97.3] vs 81.8% [72.4–88.5]). The negative predictive value (NPV; rule-out value) of IRISA-TB was significantly better than that of Xpert Ultra (87.5% [83.2–93.0] vs 64.9% [61.1–68.6]; P <.001) and ADA at the 40 IU/mL cut-point (87.5% [83.2–93.0] vs 74.1% [68.7–79.0]; P <.001). Conclusions IRISA-TB demonstrated markedly better sensitivity and NPV than Xpert Ultra and excellent specificity for the diagnosis of TPE. These data have implications for clinical practice in TB-endemic settings. [ABSTRACT FROM AUTHOR]

The article discusses a rare case of isolated tracheal mucormycosis in a patient with diabetes mellitus. The authors highlight the importance of bronchoscopic management in treating this condition, as nearly 30% of patients with isolated tracheobronchial mucormycosis may require therapeutic bronchoscopy. They describe a case in which a 49-year-old man with poorly controlled diabetes presented with airway obstruction due to mucormycosis and required airway stenting. The patient was successfully treated with a combination of bronchoscopic intervention and antifungal therapy. The article emphasizes the need for a high index of suspicion and appropriate management strategies for this uncommon condition. [Extracted from the article]

Flexible bronchoscopy (FB) is a frequently employed diagnostic procedure for evaluating respiratory disorders.[[1]],[[2]] Studies in the previous decades suggest a complication rate of 1% with FB.[[3]],[[4]] The complication rates in the contemporary era are unknown. We reviewed our bronchoscopy database to assess the frequency of major complications among subjects undergoing FB procedures without sedation. [Extracted from the article]

Background Tuberculous meningitis (TBM) mortality is high and current diagnostics perform suboptimally. We evaluated the diagnostic performance of a DNA-based assay (GeneXpert Ultra) against a new same-day immunodiagnostic assay that detects unstimulated interferon-gamma (IRISA-TB). Methods In a stage 1 evaluation, IRISA-TB was evaluated in biobanked samples from Zambia (n = 82; tuberculosis [TB] and non-TBM), and specificity in a South African biobank (n = 291; non-TBM only). Given encouraging results, a stage 2 evaluation was performed in suspected TBM patients from Zimbabwe and Malawi (n = 668). Patients were classified as having definite, probable or possible TBM, or non-TBM based on their microbiological results, cerebrospinal fluid (CSF) chemistry, and whether they received treatment. Results In the stage 1 evaluation, sensitivity and specificity of IRISA-TB were 75% and 87% in the Zambian samples, and specificity was 100% in the South African samples. In the stage 2 validation, IRISA-TB sensitivity (95% confidence interval [CI]) was significantly higher than Xpert Ultra (76.2% [55.0%–89.4%] vs 25% [8.9%–53.3%]; P =.0048) when trace readouts were considered negative. Specificity (95% CI) was similar for both assays (91.4% [88.8%–93.4%] vs 86.9% [83.4%–89.8%]). When the Xpert Ultra polymerase chain reaction product was verified by sequencing, the positive predictive value of trace readouts in CSF was 27.8%. Sensitivity of IRISA-TB was higher in human immunodeficiency virus (HIV)–infected versus uninfected participants (85.8% vs 66.7%). Conclusions As a same-day rule-in test, IRISA-TB had significantly better sensitivity than Xpert Ultra in a TB/HIV-endemic setting. An immunodiagnostic approach to TBM is promising, and further studies are warranted. [ABSTRACT FROM AUTHOR]

Background: Patients with chronic lung diseases (CLDs), defined as progressive and life-limiting respiratory conditions, experience a heavy symptom burden as the conditions become more advanced, but palliative referral rates are low and late. Prognostic tools can help clinicians identify CLD patients at high risk of deterioration for needs assessments and referral to palliative care. As current prognostic tools may not generalize well across all CLD conditions, we aim to develop and validate a general model to predict one-year mortality in patients presenting with any CLD. Methods: A retrospective cohort study of patients with a CLD diagnosis at a public hospital from July 2016 to October 2017 was conducted. The outcome of interest was all-cause mortality within one-year of diagnosis. Potential prognostic factors were identified from reviews of prognostic studies in CLD, and data was extracted from electronic medical records. Missing data was imputed using multiple imputation by chained equations. Logistic regression models were developed using variable selection methods and validated in patients seen from January 2018 to December 2019. Discriminative ability, calibration and clinical usefulness of the model was assessed. Model coefficients and performance were pooled across all imputed datasets and reported. Results: Of the 1000 patients, 122 (12.2%) died within one year. Patients had chronic obstructive pulmonary disease or emphysema (55%), bronchiectasis (38%), interstitial lung diseases (12%), or multiple diagnoses (6%). The model selected through forward stepwise variable selection had the highest AUC (0.77 (0.72–0.82)) and consisted of ten prognostic factors. The model AUC for the validation cohort was 0.75 (0.70, 0.81), and the calibration intercept and slope were − 0.14 (-0.54, 0.26) and 0.74 (0.53, 0.95) respectively. Classifying patients with a predicted risk of death exceeding 0.30 as high risk, the model would correctly identify 3 out 10 decedents and 9 of 10 survivors. Conclusions: We developed and validated a prognostic model for one-year mortality in patients with CLD using routinely available administrative data. The model will support clinicians in identifying patients across various CLD etiologies who are at risk of deterioration for a basic palliative care assessment to identify unmet needs and trigger an early referral to palliative medicine. Trial registration: Not applicable (retrospective study). [ABSTRACT FROM AUTHOR]

Background: The diagnosis of tuberculous pleurisy (TP) presents a significant challenge due to the low bacterial load in pleural effusion (PE) samples. Cell-free Mycobacterium tuberculosis DNA (cf-TB) in PE samples is considered an optimal biomarker for diagnosing TP. This study aimed to evaluate the applicability of cf-TB testing across diverse research sites with a relatively large sample size. Methods: Patients suspected of TP and presenting with clinical symptoms and radiological evidence of PE were consecutively enrolled by treating physicians from 11 research sites across 6 provinces in China between April 2020 and August 2022. Following centrifugation, sediments obtained from PE were used for Xpert MTB/RIF (Xpert) and mycobacterial culture, while the supernatants were subjected to cf-TB testing. This study employed a composite reference standard to definite TP, which was characterized by any positive result for Mycobacterium tuberculosis (MTB) through either PE culture, PE Xpert, or pleural biopsy. Results: A total of 1412 participants underwent screening, and 1344 (95.2%) were subsequently enrolled in this study. Data from 1241 (92.3%) participants were included, comprising 284 with definite TP, 677 with clinically diagnosed TP, and 280 without TP. The sensitivity of cf-TB testing in definite TP was 73.6% (95% CI 68.2–78.4), significantly higher than both Xpert (40.8%, 95% CI 35.3–46.7, P < 0.001) and mycobacterial culture (54.2%, 95% CI 48.4–59.9, P < 0.001). When clinically diagnosed TP was incorporated into the composite reference standard for sensitivity analysis, cf-TB testing showed a sensitivity of 46.8% (450/961, 95% CI 43.7–50.0), significantly higher than both Xpert (116/961, 12.1%, 95% CI 10.2–14.3, P < 0.001) and mycobacterial culture (154/961, 16.0%, 95% CI 13.8–18.5, P < 0.001). The specificities of cf-TB testing, Xpert, and mycobacterial culture were all 100.0%. Conclusions: The performance of cf-TB testing is significantly superior to that of Xpert and mycobacterial culture methods, indicating that it can be considered as the primary diagnostic approach for improving TP detection. Trial registration The trial was registered on Chictr.org.cn (ChiCTR2000031680, https://www.chictr.org.cn/showproj.html?proj=49316). [ABSTRACT FROM AUTHOR]

Lung cancer has the greatest mortality rates among both men and women and is the primary cause of cancer-related fatalities globally. Roughly 85% of occurrences of lung cancer are caused by smoking, making it the primary cause of the disease. Lung lesion analysis and, in the event that cancer is proven, therapy are becoming more and more necessary due to the rising usage of chest CT scans and lung cancer screening programs. The one-stop outpatient bronchoscopic technique, which includes tumor navigation, confirmation of malignancy, and prompt treatment, is a desirable future concept. A number of innovative ideas for bronchoscopic diagnosis and treatment are presently being considered in order to add to this idea. Better bronchoscopic navigation to the target lesion is crucial since most suspected malignant lung lesions originate in the lung's periphery. Thankfully, sophisticated bronchoscopic navigation techniques are becoming clinically available, and the discipline of interventional pulmonology is fast developing, allowing for an increasingly accurate tissue diagnosis of lung abnormalities. Furthermore, a number of bronchoscopic therapy techniques are presently being researched. [ABSTRACT FROM AUTHOR]

Background: Despite frequently reporting these problems in clinical studies, there needs to be more data on the Frequency (F) of adverse effects of chemotherapy under regular clinical care. Aim: This study aimed to outline how frequently and severely patients at treatment facilities in India reported experiencing side effects from chemotherapy during routine visits. Materials and Method: We performed prospective cohort research on people receiving lung, breast, or colorectal cancer chemotherapy. The side effects such patient’s encountered move reported through patients. For dividing a side effects' frequency, occurrence and incidence rates on kind and severity of each malignancy, cumulative incidence curves for each adverse outcome were generated. Secondary impact analysis using chi-squared statistics frequency was examined across demographic categories. Result and Conclusion: Side effect information remains available for eligible patients with a 5.7 2-months median follow-up. During the trial period, 87% of individuals had at least one adverse effect and 28% of them, most frequently tired, experienced a grade IV side effect. Constipation (76%), diarrhea (75%) and fatigue (86%) were the most prevalent adverse effects overall 459. Different cancer types and side effects have comparable prevalence and incidence rates. Older adults are less likely to report age was only demographic and adverse impact characteristics linked to occurrence of side effects. The findings of this study are the first self-reported frequency of adverse effects from chemotherapy in standard clinical treatment to be estimated in India. Treatment side effects are frequent, persistent during treatment and even lifethreatening in regular care. This study supports the idea that observational data are crucial for giving decision-makers information that is pertinent to clinical practice. [ABSTRACT FROM AUTHOR]

Conditions such as acute pancreatitis, ulcerative colitis, delayed graft function and infections caused by a variety of microorganisms, including gram-positive and gram-negative organisms, increase the risk of sepsis and therefore mortality. Immune dysfunction is a characterization of sepsis, so timely and effective treatment strategies are needed. The conventional approaches, such as antibiotic-based treatments, face challenges such as antibiotic resistance, and cytokine-based treatments have shown limited efficacy. To address these limitations, a novel approach focusing on membrane receptors, the initiators of the inflammatory cascade, is proposed. Membrane receptors such as Toll-like receptors, interleukin-1 receptor, endothelial protein C receptor, m-opioid receptor, triggering receptor expressed on myeloid cells 1, and G-protein coupled receptors play pivotal roles in the inflammatory response, offering opportunities for rapid regulation. Various membrane receptor blockade strategies have demonstrated efficacy in both preclinical and clinical studies. These membrane receptor blockades act as early stage inflammation modulators, providing faster responses compared to conventional therapies. Importantly, these blockers exhibit immunomodulatory capabilities without inducing complete immunosuppression. Finally, this review underscores the critical need for early intervention in acute inflammatory and infectious diseases, particularly those posing a risk of progressing to sepsis. And, exploring membrane receptor blockade as an adjunctive treatment for acute inflammatory and infectious diseases presents a promising avenue. These novel approaches, when combined with antibiotics, have the potential to enhance patient outcomes, particularly in conditions prone to sepsis, while minimizing risks associated with antibiotic resistance and immune suppression. [ABSTRACT FROM AUTHOR]

Background: Tuberculosis is one of the major burdens to developing nations. India is among the countries categorized by the World Health Organization (WHO) as experiencing a significant burden of TB, HIV-associated TB, and MDR/RR-TB within the context of low- and middle-income nations. Globally South East Asian and African region alone accounted for 82% of death (HIV negative), where India accounts for 36% of TB fatalities. Materials and Methods: The data was extracted from NIKSHAY web portal on TB notification cases in UP, India. The random effects meta-analysis was performed to estimate pooled proportion of TB cases in public and private notified during both the periods. Spatial analysis was used to display the spread of TB cases across the state, during both the periods. Results: A total 75 districts data on TB notified cases were available for current investigation. The pooled proportion of TB cases were 0.24 (0.21, 0.27) and 0.76 (0.73, 0.79) during COVID-19 period for private and public hospitals, respectively. Similarly, the pooled proportion of TB cases were 0.26 (0.23, 0.29) and 0.74 (0.71, 0.77) post-COVID-19 for private and public hospitals, respectively. Conclusion: The proportion of TB cases were more in public hospital as compared to private hospitals during COVID-19 period. Similarly, result was obtained in post-COVID-19 period. [ABSTRACT FROM AUTHOR]

Aim: The aim of this study was to monitor prescription patterns, clinical outcomes, and adverse drug reactions (ADR) among patients of various interstitial lung diseases (ILDs). Materials and Methods: This prospective study was conducted in the Department of Pharmacology and Therapeutics in collaboration with the Department of Respiratory Medicine, King George’s Medical University, Lucknow, for a period of 12 months (October 2020–September 2021). A total of 77 patients were enrolled after satisfying the inclusion and exclusion criteria. The prescriptions were collected, and necessary details were noted on the case report form. After completion of the study, the data were analyzed for prescription patterns, clinical outcomes, and quality of life with the help of a validated questionnaire-King’s Brief ILD (KBILD) questionnaire. At the same time, ADRs, if any, were assessed using Hartwig’s Severity Assessment Scale and Naranjo Causality Assessment Scale. Results: The most common ILD was acute/chronic hypersensitivity pneumonitis (HP). Average number of drugs per encounter was 4.45. Crepitations were the most common clinical signs. Clubbing and rhonchi were reported maximum in idiopathic pulmonary fibrosis. It was found that psychological, breathlessness and activities, chest symptoms, and total KBILD reduced significantly after 3 months as compared to baseline with a statistically significant difference as P < 0.01. ADRs were found in 23.38% (18) of the subjects. Maximum ADR reported was gastritis (9.09%), followed by hepatitis (3.90%). Conclusion: The high proportion of patients clinically diagnosed with HP in our study highlights the importance of a detailed environmental exposure history in the diagnostic evaluation of patients with ILD to avoid inaccurate diagnoses. ADR-related hospital admissions are a significant problem in the health-care system. [ABSTRACT FROM AUTHOR]

Introduction: Lung transplant (LTx) is a potential treatment option for all patients with chronic, end‑stage respiratory disease, who are refractory to optimal medical therapy or where no medical therapy exists. In India, LTx is still in its evolving stages and published literature is sparse. The current study was carried out to study the selection criteria for lung transplant and to evaluate the clinical and socio‑economic profile of patients referred for the same at a tertiary health care facility. Methods: The study was a descriptive, prospective, observational study. All adults referred for lung transplant were evaluated for clinical and laboratory profiles. All enrolled patients were assessed for presence of referral criteria, listing criteria, contraindications, and willingness for lung transplant. These patients were followed up for 2 years for transplant‑free survival, and the Cox proportional hazards model was used to determine independent predictors of all‑cause mortality. Results: A total of 103 were included in study. The most common diagnosis was interstitial lung disease (57.2%), followed by bronchiectasis (17.5%) and COPD (13.6%). Most patients were referred for LTx at an advanced stage as 90% met listing criteria. Fifty‑four (52.4%) patients had an absolute or relative contraindication to transplant; however, the majority of those contraindications were modifiable. Patients with a lower socio‑economic status were less likely to be willing for LTx. The median survival was 757 days. A 6‑minute walk distance (6MWD) lesser than 250 m was found to be an independent predictor of mortality. Conclusion: Making patients aware about lung transplant early in their treatment may give them sufficient time to come to terms with their disease and understand the risk and benefits associated. Efforts should be focused on screening and early treatment of reversible contraindications for the eligible patients. Patients with 6MWD < 250 m are at increased risk of mortality. [ABSTRACT FROM AUTHOR]

Non-resolving consolidation refers to the persistence of radiographic abnormalities beyond the anticipated timeframe. Conditions such as infection, malignancy, inflammatory disorders, and connective tissue diseases can all manifest as non-resolving consolidation. We share a clinicopathological case study involving a 30-year-old male who exhibits nonresolving consolidation accompanied by hepatosplenomegaly. [ABSTRACT FROM AUTHOR]

Sir, Endobronchial tuberculosis is a well-recognized clinical entity; however, it is uncommon without pulmonary parenchymal or mediastinal lymph node involvement.[[1]] Endobronchial tuberculosis is further classified as exudative, granular and ulcerative.[[2]] Herein, we report a rare presentation of tuberculosis manifesting as a solitary ulcer in the right main bronchus. The anatomic location of the ulcer (beneath which the right inferior pulmonary vein would be expected) and the depth of the ulcer should have deterred us from obtaining a biopsy. [Extracted from the article]

Background: A bronchopleural fistula (BPF) occurs when an abnormal connection forms between the bronchial tubes and pleural cavity, often due to surgery, infection, trauma, radiation, or chemotherapy. The outcomes of both surgical and bronchoscopic treatments frequently prove to be unsatisfactory. Case presentation: Here, we report a case of successful bronchoscopic free fat pad transplantation combined with platelet-rich plasma, effectively addressing a post-lobectomy BPF. Contrast-enhanced chest tomography revealed pleural thickening with heterogeneous consolidations over the right upper and middle lobes, indicative of destructive lung damage and bronchiectasis. The patient underwent thoracoscopic bilobectomy of the lungs. During surgery, severe adhesions and calcification of the chest wall and lung parenchyma were observed. The entire hilar structure was calcified, presenting challenges for dissection, despite the assistance of energy devices. Bronchoscopic intervention was required, during which two abdominal subcutaneous fat pads were retrieved. Conclusion: This innovative approach offers promise in the management of BPF and signals potential advancements in enhancing treatment efficacy and patient recovery. [ABSTRACT FROM AUTHOR]

Purpose of Review: Inhaled antifungals achieve high lung concentrations with minimal systemic adverse events. Despite being available for over five decades, data supporting their use outside the mold-active prophylaxis setting are lacking. Herein, we review the recent evidence on inhaled antifungals in treating pulmonary aspergillosis (allergic, chronic, and invasive) and mucormycosis. Recent Findings: Several antifungals have recently been evaluated, including repurposed and newer inhaled agents (opelconazole). Inhaled amphotericin B deoxycholate (in pulmonary mucormycosis) and liposomal formulation (in invasive aspergillosis) were safely used in two recent randomized trials. However, both these small trials failed to demonstrate added benefit with adjunctive inhaled amphotericin. In allergic bronchopulmonary aspergillosis, nebulized amphotericin B may prolong the time-to-exacerbation when used in patients experiencing frequent exacerbations. Summary: The last decade has witnessed considerable progress in inhaled antifungals. Ongoing trials will likely offer hope for managing allergic and invasive pulmonary mycoses in the future. [ABSTRACT FROM AUTHOR]

We retrospectively reviewed consecutive cases of mucormycosis reported from a tertiary-care center in India to determine the clinical and mycologic characteristics of emerging Rhizopus homothallicus fungus. The objectives were ascertaining the proportion of R. homothallicus infection and the 30-day mortality rate in rhino-orbital mucormycosis attributable to R. homothallicus compared with R. arrhizus. R. homothallicus accounted for 43 (6.8%) of the 631 cases of mucormycosis. R. homothallicus infection was independently associated with better survival (odds ratio [OR] 0.08 [95% CI 0.02-0.36]; p = 0.001) than for R. arrhizus infection (4/41 [9.8%] vs. 104/266 [39.1%]) after adjusting for age, intracranial involvement, and surgery. We also performed antifungal-susceptibility testing, which indicated a low range of MICs for R. homothallicus against the commonly used antifungals (amphotericin B [0.03-16], itraconazole [0.03-16], posaconazole [0.03-8], and isavuconazole [0.03-16]). 18S gene sequencing and amplified length polymorphism analysis revealed distinct clustering of R. homothallicus. [ABSTRACT FROM AUTHOR]

Background: India accounts for about one-quarter of people contracting tuberculosis (TB) disease annually and nearly one-third of TB deaths globally. Many Indians do not navigate all care cascade stages to receive TB treatment and achieve recurrence-free survival. Guided by a population/exposure/comparison/outcomes (PECO) framework, we report findings of a systematic review to identify factors contributing to unfavorable outcomes across each care cascade gap for TB disease in India. Methods and findings: We defined care cascade gaps as comprising people with confirmed or presumptive TB who did not: start the TB diagnostic workup (Gap 1), complete the workup (Gap 2), start treatment (Gap 3), achieve treatment success (Gap 4), or achieve TB recurrence-free survival (Gap 5). Three systematic searches of PubMed, Embase, and Web of Science from January 1, 2000 to August 14, 2023 were conducted. We identified articles evaluating factors associated with unfavorable outcomes for each gap (reported as adjusted odds, relative risk, or hazard ratios) and, among people experiencing unfavorable outcomes, reasons for these outcomes (reported as proportions), with specific quality or risk of bias criteria for each gap. Findings were organized into person-, family-, and society-, or health system-related factors, using a social-ecological framework. Factors associated with unfavorable outcomes across multiple cascade stages included: male sex, older age, poverty-related factors, lower symptom severity or duration, undernutrition, alcohol use, smoking, and distrust of (or dissatisfaction with) health services. People previously treated for TB were more likely to seek care and engage in the diagnostic workup (Gaps 1 and 2) but more likely to suffer pretreatment loss to follow-up (Gap 3) and unfavorable treatment outcomes (Gap 4), especially those who were lost to follow-up during their prior treatment. For individual care cascade gaps, multiple studies highlighted lack of TB knowledge and structural barriers (e.g., transportation challenges) as contributing to lack of care-seeking for TB symptoms (Gap 1, 14 studies); lack of access to diagnostics (e.g., X-ray), non-identification of eligible people for testing, and failure of providers to communicate concern for TB as contributing to non-completion of the diagnostic workup (Gap 2, 17 studies); stigma, poor recording of patient contact information by providers, and early death from diagnostic delays as contributing to pretreatment loss to follow-up (Gap 3, 15 studies); and lack of TB knowledge, stigma, depression, and medication adverse effects as contributing to unfavorable treatment outcomes (Gap 4, 86 studies). Medication nonadherence contributed to unfavorable treatment outcomes (Gap 4) and TB recurrence (Gap 5, 14 studies). Limitations include lack of meta-analyses due to the heterogeneity of findings and limited generalizability to some Indian regions, given the country's diverse population. Conclusions: This systematic review illuminates common patterns of risk that shape outcomes for Indians with TB, while highlighting knowledge gaps—particularly regarding TB care for children or in the private sector—to guide future research. Findings may inform targeting of support services to people with TB who have higher risk of poor outcomes and inform multicomponent interventions to close gaps in the care cascade. Tulip A. Jhaveri and team report findings of a systematic review to identify factors contributing to unfavorable outcomes across each care cascade gap for tuberculosis disease in India. Author summary: Why was this study done?: India has the highest tuberculosis (TB) incidence, accounting for about one-quarter of people with TB disease and nearly one-third of TB deaths globally. Many Indians with TB do not traverse all care stages needed to receive treatment and achieve an optimal long-term outcome, with serial losses of people across these stages referred to as the "care cascade." Understanding why losses of people with TB disease occur across the care cascade is crucial to inform interventions to prevent unfavorable outcomes. What did the researchers do and find?: We conducted 3 systematic searches to identify papers published from 2000 to 2023. We extracted information from these studies on risk factors for unfavorable outcomes for each care cascade gap, as well as reasons reported by people with TB who experienced unfavorable outcomes and were surveyed by researchers. Some factors contributed to losses at multiple care cascade stages, including male sex, older age, poverty-related factors, history of prior TB treatment, lower symptom severity or duration, undernutrition, alcohol use, smoking, and dissatisfaction with health services. Other barriers included: lack of TB knowledge and transportation barriers to clinic contributing to lack of care-seeking (Gap 1), poor accessibility of testing and failure to identify people eligible for testing contributing to non-completion of the diagnostic workup (Gap 2), early deaths from diagnostic delays and poor recording of contact information contributing to losses of people before treatment (Gap 3), lack of TB knowledge and depression contributing to unfavorable treatment outcomes (Gap 4), and medication nonadherence contributing to unfavorable treatment outcomes and TB recurrence (Gaps 4 and 5). What do these findings mean?: Reasons for losses of people with TB disease across the care cascade are complex, vary by care cascade gap, and involve patient- and health system-related barriers. India's TB program should target additional services to people with higher risk of poor outcomes and develop multicomponent interventions to address the diverse challenges faced by people with TB. Study limitations include lack of meta-analyses (i.e., estimation of the average effect of each risk factor by combining findings across studies), and caution is required when applying findings across India's diverse population. [ABSTRACT FROM AUTHOR]

Background: Tuberculosis (TB) and COVID-19 co-infection poses a significant global health challenge with increased fatality rates and adverse outcomes. However, the existing evidence on the epidemiology and treatment of TB-COVID co-infection remains limited. Methods: This updated systematic review aimed to investigate the prevalence, fatality rates, and treatment outcomes of TB-COVID co-infection. A comprehensive search across six electronic databases spanning November 1, 2019, to January 24, 2023, was conducted. The Joanna Briggs Institute Critical Appraisal Checklist assessed risk of bias of included studies, and meta-analysis estimated co-infection fatality rates and relative risk. Results: From 5,095 studies screened, 17 were included. TB-COVID co-infection prevalence was reported in 38 countries or regions, spanning both high and low TB prevalence areas. Prevalence estimates were approximately 0.06% in West Cape Province, South Africa, and 0.02% in California, USA. Treatment approaches for TB-COVID co-infection displayed minimal evolution since 2021. Converging findings from diverse studies underscored increased hospitalization risks, extended recovery periods, and accelerated mortality compared to single COVID-19 cases. The pooled fatality rate among co-infected patients was 7.1% (95%CI: 4.0% ~ 10.8%), slightly lower than previous estimates. In-hospital co-infected patients faced a mean fatality rate of 11.4% (95%CI: 5.6% ~ 18.8%). The pooled relative risk of in-hospital fatality was 0.8 (95% CI, 0.18–3.68) for TB-COVID patients versus single COVID patients. Conclusion: TB-COVID co-infection is increasingly prevalent worldwide, with fatality rates gradually declining but remaining higher than COVID-19 alone. This underscores the urgency of continued research to understand and address the challenges posed by TB-COVID co-infection. Author summary: Tuberculosis (TB) and COVID-19, both highly infectious diseases, have posed significant global health challenges, particularly in low/middle-income countries (LMICs) with limited medical resources. Our research highlights that TB-COVID co-infection remains a substantial concern, impacting regions with varying TB burdens. The predominant treatment approach for TB-COVID co-infection has not notably evolved since our earlier study in 2021. It typically involves a combination of the recommended TB regimen and standard COVID-19 treatment. Our analysis consistently shows that individuals with TB-COVID co-infection are at heightened risk of hospitalization, protracted recovery periods, and accelerated mortality compared to those with sole COVID-19 infections. Remarkably, we found limited information on the post-COVID-19 condition of co-infected patients. One study indicated a higher prevalence of anxiety symptoms, highlighting the potential psychological toll of TB-COVID co-infection. Although the fatality rate has gradually decreased, it remains notably higher than that of COVID-19 alone. Our findings underscore the urgent need for global collaboration to address the complex challenges posed by TB-COVID co-infection, particularly in countries with limited medical resources. [ABSTRACT FROM AUTHOR]

Background: The treatment response to corticosteroids in patients with sarcoidosis is highly variable. CD4+ T cells are central in sarcoid pathogenesis and their phenotype in peripheral blood (PB) associates with disease course. We hypothesized that the phenotype of circulating T cells in patients with sarcoidosis may correlate with the response to prednisone treatment. Therefore, we aimed to correlate frequencies and phenotypes of circulating T cells at baseline with the pulmonary function response at 3 and 12 months during prednisone treatment in patients with pulmonary sarcoidosis. Methods: We used multi-color flow cytometry to quantify activation marker expression on PB T cell populations in 22 treatment-naïve patients and 21 healthy controls (HCs). Pulmonary function tests at baseline, 3 and 12 months were used to measure treatment effect. Results: Patients with sarcoidosis showed an absolute forced vital capacity (FVC) increase of 14.2% predicted (± 10.6, p < 0.0001) between baseline and 3 months. Good response to prednisone (defined as absolute FVC increase of ≥ 10% predicted) was observed in 12 patients. CD4+ memory T cells and regulatory T cells from patients with sarcoidosis displayed an aberrant phenotype at baseline, compared to HCs. Good responders at 3 months had significantly increased baseline proportions of PD-1+CD4+ memory T cells and PD-1+ regulatory T cells, compared to poor responders and HCs. Moreover, decreased fractions of CD25+ cells and increased fractions of PD-1+ cells within the CD4+ memory T cell population correlated with ≥ 10% FVC increase at 12 months. During treatment, the aberrantly activated phenotype of memory and regulatory T cells reversed. Conclusions: Increased proportions of circulating PD-1+CD4+ memory T cells and PD-1+ regulatory T cells and decreased proportions of CD25+CD4+ memory T cells associate with good FVC response to prednisone in pulmonary sarcoidosis, representing promising new blood biomarkers for prednisone efficacy. Trial registration: NL44805.078.13 [ABSTRACT FROM AUTHOR]

This document discusses a rare case of anomalous systemic arterial supply to the lung without sequestration. The case involves a 43-year-old male who was incidentally diagnosed with this congenital anomaly during a routine medical examination. The patient had a history of hemoptysis 10 years prior, which was managed conservatively. The article provides an overview of systemic arterial supply to the lung and emphasizes the rarity of this specific anomaly. [Extracted from the article]

Background: Sarcoidosis is a systemic granulomatous disease of unknown etiology primarily affecting the lungs. Treatment is needed when disease symptoms worsen and organ function deteriorates. In pulmonary sarcoidosis, prednisone and methotrexate (MTX) are the most common anti-inflammatory therapies. However, there is large inter-patient variability in response to treatment, and predictive response markers are currently lacking. Objective: In this study, we investigated the predictive potential of biomarkers in extracellular vesicles (EVs) isolated from biobanked serum of patients with pulmonary sarcoidosis stored prior to start of therapy. Methods: Protein concentrations of a four-protein test panel of inflammatory proteins were measured in a discovery (n = 16) and replication (n = 129) cohort of patients with sarcoidosis and 47 healthy controls. Response to therapy was defined as an improvement of the absolute score of > 5% forced vital capacity (FVC) and/or > 10% diffusion lung of carbon monoxide (DLCO) after 24 weeks compared to baseline (before treatment). Results: Serum protein levels differed between EV fractions and serum, and between sarcoidosis cases and controls. Serpin C1 concentrations in the low density lipid particle EV fraction were lower at baseline in the group of patients with a good response to MTX treatment in both the discovery cohort (p = 0.059) and in the replication cohort (p = 0.032). EV Serpin C1 showed to be a significant predictor for response to treatment with MTX (OR 0.4; p = 0.032). Conclusion: This study shows that proteins isolated from EVs harbor a distinct signal and have potential as new predictive therapy response biomarkers in sarcoidosis. [ABSTRACT FROM AUTHOR]

As an autoimmune disease, the persistent systemic inflammatory response associated with connective tissue disease (CTD) is involved in the development of venous thromboembolism (VTE). However, clinical data showed that the risk of VTE in patients differed between subtypes of CTD, suggesting that different subtypes may have independent mechanisms to promote the development of VTE, but the specific mechanism lacks sufficient research at present. The development of pulmonary fibrosis also contributes to the development of VTE, and therefore, patients with CTD-associated interstitial lung disease (CTD-ILD) may be at higher risk of VTE than patients with CTD alone or patients with ILD alone. In addition, the activation of the coagulation cascade response will drive further progression of the patient's pre-existing pulmonary fibrosis, which will continue to increase the patient's risk of VTE and adversely affect prognosis. Currently, the treatment for CTD-ILD is mainly immunosuppressive and antirheumatic therapy, such as the use of glucocorticoids and janus kinase-inhibitors (JAKis), but, paradoxically, these drugs are also involved in the formation of patients' coagulation tendency, making the clinical treatment of CTD-ILD patients with a higher risk of developing VTE challenging. In this article, we review the potential risk factors and related mechanisms for the development of VTE in CTD-ILD patients to provide a reference for clinical treatment and prevention. [ABSTRACT FROM AUTHOR]

Cisplatin (DDP) resistance, often leading to first-line chemotherapy failure in non-small cell lung cancer (NSCLC), poses a significant challenge. MiR-219a-5p has been reported to enhance the sensitivity of human NSCLC to DDP. However, free miR-219a-5p is prone to degradation by nucleases in the bloodstream, rendering it unstable. In light of this, our study developed an efficient nanodrug delivery system that achieved targeted delivery of DDP and miR-219a-5p by modifying liposomes with folate (FA). Based on the results of material characterization, we successfully constructed a well-dispersed and uniformly sized (approximately 135.8 nm) Lipo@DDP@miR-219a-5p@FA nanodrug. Agarose gel electrophoresis experiments demonstrated that Lipo@DDP@miR-219a-5p@FA exhibited good stability in serum, effectively protecting miR-219a-5p from degradation. Immunofluorescence and flow cytometry experiments revealed that, due to FA modification, Lipo@DDP@miR-219a-5p@FA could specifically bind to FA receptors on the surface of tumor cells (A549), thus enhancing drug internalization efficiency. Safety evaluations conducted in vitro demonstrated that Lipo@DDP@miR-219a-5p@FA exhibited no significant toxicity to non-cancer cells (BEAS-2B) and displayed excellent blood compatibility. Cellular functional experiments, apoptosis assays, and western blot demonstrated that Lipo@DDP@miR-219a-5p@FA effectively reversed DDP resistance in A549 cells, inhibited cell proliferation and migration, and further promoted apoptosis. In summary, the Lipo@DDP@miR-219a-5p@FA nanodrug, through specific targeting of cancer cells and reducing their resistance to DDP, significantly enhanced the anti-NSCLC effects of DDP in vitro, providing a promising therapeutic option for the clinical treatment of NSCLC. [ABSTRACT FROM AUTHOR]

Background: The second most common cancer and the main cause of death from cancer worldwide is lung cancer. The stage of the cancer, mutation, and histological type all affect the prognosis and course of treatment. There is no adequate data about histological subtypes lung cancer in our area. The aim of this study is to evaluate the smoking status, histological subtypes, clinicoepidemiological profile, and interdependencies among those suffering from lung cancer. Materials and Methods: This cross-sectional study was conducted in Department of Pulmonary Medicine, Government Medical College, Thrissur, Kerala, India. From May 2, 2021, until May 7, 2022. Histopathologicaly confirmed lung cancer patients were studied. The data was collected by using a semi-structured proforma, and SPSS 20 was used for analysis. Results: The mean age of the patients (n=124) was 63.42 + 9.11 (SD) years. The common symptoms were cough (71.8%), breathlessness (62.9%), chest pain (35.5%), and loss of weight (31.5%). Among the patients 86.3% are males and 80.6% are smokers. Adenocarcinoma was the commonest histopathological subtype (45.9%) followed by squamous cell carcinoma (37.9%), small cell carcinoma (10.5%) and other neuroendocrine tumors (5.6%). Squamous cell carcinoma was the commonest subtype among males (42.1%) and smokers (44.6%). Adenocarcinoma remained commonest among females (82.3%) and non-smokers (87%). Cough was significantly higher in squamous cell and small cell carcinomas (p=0.04). Dyspnea remained the most prevalent symptom in adenocarcinoma (64.9%). Conclusion: Adenocarcinoma was the commonest subtype. Squamous cell carcinoma had higher prevalence among males and smokers; adenocarcinoma was higher among females and non-smokers. The commonest symptom was cough. Cough was significantly higher in squamous cell and small cell carcinomas. Dyspnoea was the most prevalent symptom in adenocarcinoma. [ABSTRACT FROM AUTHOR]