Explore the vast range of titles available.

This study was conducted to get a complete clinical and mycological picture of invasive aspergillosis (IA) in respiratory medicine ICU of a tertiary care hospital. From the cohort of 235 patients only one had proven IA. Based on AspICU algorithm, 21 had putative IA (8.9%), 12 were colonised (5.1%). Adjusting the confounding factors, significant risk factors for IA were chronic obstructive pulmonary disease (COPD), temperature of ≥38°C, pneumonia and acute respiratory distress syndrome (ARDS). The best predictor of IA was AspICU algorithm (AUC, 1) followed by serum galactomannan antigen (GM) cut-off (≥1.24) calculated based on AspICU algorithm (AUC, 0.822). For 37% of patients, IA diagnoses was made earlier with serum GM than radiology. There were 70/235 (29.8%) deaths within 30 days of enrolment in the study. Aspergillus culture positivity (34/235, 14.5%) was associated with very high mortality (27/34, 79.4%), (p<0.05). The best predictor of mortality was GM cut-off (≥1.24) calculated based on AspICU algorithm (AUC, 0.835). This study imparts the focus on relatively underestimated Aspergillus infections prevalent in ICUs. The AspICU algorithm was found to be useful over others for IA diagnosis. The prognostic usefulness of serum GM antigen detection test highlighted overlooking the same may not be rewarding for the outcome of IA suspected ICU subpopulation.

Background Statins and aspirin have been proposed for treatment of COVID-19 because of their anti-inflammatory and anti-thrombotic properties. Several observational studies have shown favourable results. There is a need for a randomised controlled trial. Methods In this single-center, open-label, randomised controlled trial, 900 RT-PCR positive COVID-19 patients requiring hospitalisation, were randomly assigned to receive either atorvastatin 40 mg (Group A, n = 224), aspirin 75 mg (Group B, n = 225), or both (Group C, n = 225) in addition to standard of care for 10 days or until discharge whichever was earlier or only standard of care (Group D, n = 226). The primary outcome variable was clinical deterioration to WHO Ordinal Scale for Clinical Improvement ≥ 6. The secondary outcome was change in serum C-reactive protein, interleukin-6, and troponin I. Results The primary outcome occurred in 25 (2.8%) patients: 7 (3.2%) in Group A, 3 (1.4%) in Group B, 8 (3.6%) in Group C, and 7 (3.2%) in Group D. There was no difference in primary outcome across the study groups (P = 0.463). Comparison of all patients who received atorvastatin or aspirin with the control group (Group D) also did not show any benefit [Atorvastatin: HR 1.0 (95% CI 0.41–2.46) P = 0.99; Aspirin: HR 0.7 (95% CI 0.27–1.81) P = 0.46]. The secondary outcomes revealed lower serum interleukin-6 levels among patients in Groups B and C. There was no excess of adverse events. Conclusions Among patients admitted with mild to moderate COVID-19 infection, additional treatment with aspirin, atorvastatin, or a combination of the two does not prevent clinical deterioration. Trial Registry Number CTRI/2020/07/026791 ( http://ctri.nic.in ; registered on 25/07/2020)

Background Lignin and xylan are important determinants of cell wall structure and lignocellulosic biomass digestibility. Genetic manipulations that individually modify either lignin or xylan structure improve polysaccharide digestibility. However, the effects of their simultaneous modifications have not been explored in a similar context. Here, both individual and combinatorial modification in xylan and lignin was studied by analysing the effect on plant cell wall properties, biotic stress responses and integrity sensing. Results Arabidopsis plant co-harbouring mutation in FERULATE 5-HYDROXYLASE ( F5H ) and overexpressing Aspergillus niger acetyl xylan esterase (35S: An AXE1) were generated and displayed normal growth attributes with intact xylem architecture. This fah1-2 /35S: An AXE1 cross was named as h ype r G lignin and hyp o ac etylated (HrGHypAc) line. The HrGHypAc plants showed increased crystalline cellulose content with enhanced digestibility after chemical and enzymatic pre-treatment. Moreover, both parents and HrGHypAc without and after pre-treating with glucuronyl esterase and alpha glucuronidase exhibited an increase in xylose release after xylanase digestion as compared to wild type. The de-pectinated fraction in HrGHypAc displayed elevated levels of xylan and cellulose. Furthermore, the transcriptomic analysis revealed differential expression in cell wall biosynthetic, transcription factors and wall-associated kinases genes implying the role of lignin and xylan modification on cellular regulatory processes. Conclusions Simultaneous modification in xylan and lignin enhances cellulose content with improved saccharification efficiency. These modifications loosen cell wall complexity and hence resulted in enhanced xylose and xylobiose release with or without pretreatment after xylanase digestion in both parent and HrGHypAc. This study also revealed that the disruption of xylan and lignin structure is possible without compromising either growth and development or defense responses against Pseudomonas syringae infection.

Background Post-Covid Pulmonary Fibrosis (PCPF) has emerged as a significant global issue associated with a poor quality of life and significant morbidity. Currently, our understanding of the molecular pathways of PCPF is limited. Hence, in this study, we performed whole transcriptome sequencing of the RNA isolated from the bronchoalveolar lavage (BAL) samples of PCPF and compared it with idiopathic pulmonary fibrosis (IPF) and non-ILD (Interstitial Lung Disease) control to understand the gene expression profile and associated pathways. Methods BAL samples from PCPF ( n  = 3), IPF ( n  = 3), and non-ILD Control ( n  = 3) (individuals with apparent healthy lung without interstitial lung disease) groups were obtained and RNA were isolated for whole transcriptomic sequencing. Differentially Expressed Genes (DEGs) were determined followed by functional enrichment analysis and qPCR validation. Results A panel of differentially expressed genes were identified in bronchoalveolar lavage fluid cells (BALF) of PCPF as compare to control and IPF. Our analysis revealed dysregulated pathways associated with cell cycle regulation, immune responses, and neuroinflammatory processes. Real-time validation further supported these findings. The PPI network and module analysis shed light on potential biomarkers and underscore the complex interplay of molecular mechanisms in PCPF. The comparison of PCPF and IPF identified a significant downregulation of pathways that were more prominent in IPF. Conclusion This investigation provides crucial insights into the molecular mechanism of PCPF and also outlines avenues for prospective research and the development of therapeutic approaches.

CD4(+)CD25(+)Foxp3(+) regulatory T cells (Treg) and programmed death-1 (PD-1) molecules have emerged as pivotal players in immune suppression of chronic diseases. However, their impact on the disease severity, therapeutic response and restoration of immune response in human tuberculosis remains unclear. Here, we describe the possible role of Treg cells, their M. tuberculosis driven expansion and contribution of PD-1 pathway to the suppressive function of Treg cells among pulmonary tuberculosis (PTB) patients. Multicolor flow cytometry, cell culture, cells sorting and ELISA were employed to execute the study. Our results showed significant increase in frequency of antigen-reactive Treg cells, which gradually declined during successful therapy and paralleled with decline of M. tuberculosis-specific IL-10 along with elevation of IFN-γ production, and raising the IFN-γ/IL-4 ratio. Interestingly, persistence of Treg cells tightly correlated with MDR tuberculosis. Also, we show that blocking PD-1/PD-L1 pathway abrogates Treg-mediated suppression, suggesting that the PD-1/PD-L1 pathway is required for Treg-mediated suppression of the antigen-specific T cells. Treg cells possibly play a role in dampening the effector immune response and abrogating PD-1 pathway on Treg cells significantly rescued protective T cell response, suggesting its importance in immune restoration among tuberculosis patients.

Small cell lung carcinomas (SCLC) are aggressive tumors with high propensity to metastasize. Recent NCCN guidelines have incorporated immunotherapy in extensive stage SCLC. Limited benefit in few patients compounded by side effects of unwonted immune-checkpoint-inhibitor (ICPI) usage necessitates identification of potential biomarkers predicting response to ICPIs. Attempting this, we analysed expression of various immunoregulatory molecules in tissue biopsies and paired blood samples of SCLC patients. In 40 cases, immunohistochemistry for expression of immune inhibitory receptors CTLA-4, PD-L1 and IDO1 was performed. Matched blood samples were quantified for IFN-γ, IL-2, TNF-α and sCTLA-4 levels using immunoassay and additionally for IDO1 activity (Kynurenine/Tryptophan ratio) using LC–MS. Immunopositivity for PD-L1, IDO1 and CTLA-4 was identified in 9.3%, 6.2% and 71.8% cases, respectively. Concentration of serum IFN-γ (p-value < 0.001), TNF-α (p-value = 0.025) and s-CTLA4 (p-value = 0.08) were higher in SCLC patients while IL-2 was lower (p-value = 0.003) as compared to healthy controls. IDO1 activity was significantly elevated in SCLC cohort (p-value = 0.007). We proffer that SCLC patients show immune suppressive milieu in their peripheral circulation. Analysis of CTLA4 immunohistochemical expression along with s-CTLA4 levels appears prospective as biomarkers for predicting responsiveness to ICPIs. Additionally, evaluation of IDO1 appears cogent both as prognostic marker and potential therapeutic target as well.

Background: Chronic obstructive pulmonary disease (COPD) is a progressive lung disorder characterized by poorly reversible airway obstruction. COPD being an inflammatory disorder has been proposed to have an imbalance between proinflammatory and anti‐inflammatory factors. Regulatory T cells (Tregs) being a negative regulator of immune response have been observed to play an important role in other inflammatory diseases as well as animal models of inflammation. Objective : This study is aimed at assessing the suppressive functions of circulatory Tregs and examining the inductive capacity of naive CD4+ T cells to generate induced Tregs. Methods: The study was conducted in 20 COPD patients (smokers n = 10; reformed smokers n = 10) and 20 age‐matched healthy controls (smokers n = 10; nonsmokers n = 10). Peripheral blood mononuclear cells were isolated from blood using Ficoll density gradient separation. The suppressive functions were evaluated by assessing the proliferation of T responder cells (CD4+CD25−) in the presence of circulatory Tregs (CD4+CD25+) under polyclonal stimulation. In addition, cytokine‐mediated suppression was assessed in the culture supernatants of the suppression assay. Inductive capacity was assessed by stimulating naive CD4+ T cells to generate iTregs in the presence of anti‐CD3, IL‐2, and TGF‐ β 1. Results: The percent suppression of T responder cells by Tregs was significantly lower in COPD smokers ( p = 0.03) and COPD reformed smokers ( p = 0.04) as compared to control smokers. On the assessment of cytokine‐mediated suppression, significantly reduced IL‐2 in COPD S as compared to COPD RS ( p < 0.05) and reduced IL‐10 and TGFß1 in COPD S as compared to CNS ( p < 0.05) and CS ( p < 0.05) was observed in the culture supernatants of suppression assay. In addition, a significantly higher frequency of iTregs with phenotype CD4+CD25+CD45RA+CD127− was observed in COPD S as compared to COPD RS ( p < 0.01). Discussion: Characteristics changes were observed in patients with COPD. The compromised Tregs function, despite the increase in systemic inflammation, suggests a potential role of these cells in the pathogenesis of the disease.

There is uncertainty regarding the optimal next imaging modality for identifying likely malignant pulmonary lesions in patients with abnormal chest radiography, with or without respiratory symptoms. We compared the diagnostic accuracy of chest contrast-enhanced computed tomography (CECT) and positron emission tomography or positron emission tomography-computed tomography (PET/PET-CT) for identifying malignant pulmonary lesions. Systematic review and meta-analysisData sources and methods:We searched the PubMed, Embase, Scopus, and Cochrane CENTRAL databases to identify head-to-head diagnostic accuracy studies comparing CECT and PET/PET-CT for their ability to differentiate between benign and malignant pulmonary lesions. The risk of bias of included studies was assessed using the Quality Assessment of Diagnostic Accuracy Studies - Comparative (QUADAS-C) tool. Meta-analysis was performed using the bivariate random effects model. We included eight studies, comprising a total of 873 subjects. The pooled sensitivity and specificity of CECT (850 lesions) were 0.93 (95% CI, 0.89-0.96;  = 24.99%) and 0.54 (95% CI, 0.32-0.75;  = 84.00%). The pooled sensitivity and specificity of PET/PET-CT (851 lesions) were 0.87 (95% CI, 0.78-0.93;  = 65.15%) and 0.83 (95% CI, 0.63-0.94;  = 73.23%). Compared to CECT, PET/PET-CT had a lower relative sensitivity (relative ratio [RR], 0.93; 95% CI, 0.89-0.97;  < 0.01) and a higher relative specificity (RR, 1.69; 95% CI, 1.18-2.41;  < 0.01). After excluding the study with the largest sample size, PET/PET-CT was not less sensitive than CECT (RR, 0.99; 95% CI, 0.94-1.04;  = 0.73). There was a high/unclear risk of bias and applicability concerns in the population domain in six out of eight studies. Based on limited evidence with applicability concerns, CECT of the chest may have a higher sensitivity but lower specificity than PET/PET-CT for identifying malignant lesions among patients with suspected lung cancer. The protocol for the systematic review was prospectively registered on PROSPERO (CRD42024590904).

Lung cancer continues to be a menace to the managing clinician in spite of several advances in the diagnostics and therapeutics of this dreaded disease. Since the recognition of epidermal growth factor receptor (EGFR) exon 19 and 21 mutations in the pathogenesis of non-small cell lung cancer (NSCLC) as driver mutation, substantial progress has been made in terms of diagnosis as well as management protocols for nonsquamous NSCLC. The concept of mutation testing in blood or blood products is termed as a liquid biopsy. [...]there is a growing utility of rapid plasma genotyping or “liquid biopsies” which employs circulating tumor DNA (ctDNA) in peripheral blood for molecular profiling. Liquid biopsy, in this sense, represents the tumor burden as a whole rather than a part of it. [...]digital droplet PCR can determine the absolute quantity of mutant EGFR levels in plasma samples and can also be used to monitor treatment response or disease progression serially.

Ethambutol use may lead to permanent vision loss by inducing a dose- and duration-dependent optic neuropathy. This has been of concern to ophthalmologists and physicians both; however, ethambutol continues to be used because of its anti-mycobacterial action with relative systemic safety. Recently, the guidelines of the Revised National Tuberculosis Control Programme of India have been revised to allow for fixed dose and longer duration of ethambutol use; this is likely to result in an increase in vision-threatening adverse effects. Taking cognizance of this, neuro-ophthalmologists, infectious disease specialists, and scientists met under the aegis of the Indian Neuro-Ophthalmology Society to deliberate on prevention, early diagnosis, and management of ethambutol-related toxic optic neuropathy. The recommendations made by the expert group focus on early suspicion of ethambutol toxicity through screening at the physician's office and opportunistic screening by the ophthalmologist. Further, they focus on an early diagnosis through identification of specific clinical biomarkers and on management in way of early stoppage of the drug and supportive therapy. This statement also describes the mechanism of reporting a case of toxic optic neuropathy through the Pharmacovigilance Programme of India and emphasizes the need for spreading awareness regarding vision-threatening adverse effects among patients and healthcare workers.