Widespread adoption of transbronchial lung cryobiopsy (TBLC) using a 1.9 or 2.4 mm touch cryoprobe in interstitial lung disease (ILD) has been limited by high bleeding risk. Recent studies have demonstrated that the 1.1 mm cryoprobe via conventional bronchoscope may achieve diagnostic yields comparable to larger probes while maintaining a favorable safety profile. Studies of the 1.1 mm touch cryoprobe in the diagnosis of ILD have been flawed and conflicting.

The aim of this study is to describe the complication rate, diagnostic yield, and factors that increase diagnostic yield of TBLC using a 1.1 mm touch cryoprobe in patients with ILD.

The retrospective cohort study included patients that were prospectively identified in the ILD clinic registry at University of Texas Southwestern Medical Center (UTSW) who underwent TBLC from 2022-2026. Procedural characteristics were recorded. Patients were assigned a pre-TBLC, post-TBLC, and final diagnosis.

This study demonstrates that TBLC using a 1.1 mm probe added to BAL significantly increases diagnostic yield with an 11% risk of pneumothorax and a 6.5% risk of bleeding. The combination of BAL and TBLC was diagnostic in 27 (43.5%) of patients and led to a change in diagnosis in 27 (43.5%) of patients. The number of TBLC samples taken is associated with a higher diagnostic yield.

The diagnostic yield and complication rates of the 1.1 mm touch probe in our study are higher than previously reported studies with TBBx but lower than 1.9 and 2.4 mm touch probes, though there was no direct comparison group in our study. To increase yield of the procedure, multiple lobes should be biopsied and more samples taken.

There is limited evidence on how reduced healthcare resource utilization during the COVID-19 pandemic has affected the detection of inflammatory and immunologic diseases. We aimed to describe the observed incidence rates (IRs) of asthma, atopic dermatitis (AD), and multiple sclerosis (MS) before, during, and after the pandemic. Individuals aged ≥6 years were identified in Optum's de-identified Clinformatics® Data Mart Database from 2018 to 2022 to make 20 season-based cohorts. Age- and sex-standardized IRs of asthma, AD, and MS were estimated. Incidence rate ratios (IRR) and 95% confidence intervals (CI) were calculated comparing IRs in seasonal cohorts in 2019-2022 to the corresponding timeframe in 2018. Compared to spring 2018, IRs of asthma, AD, and MS in spring 2020 decreased by 14% (IRR: 0.86, 95% CI: 0.84-0.87), 28% (IRR: 0.72, 95% CI: 0.69-0.75), and 23% (IRR: 0.77, 95% CI: 0.68-0.87), respectively. The observed incidence reduction was most profound in children (6-11 years) and adolescents (12-17 years), followed by senior adults (≥65 years). There was no sex difference. IRs returned to or exceeded pre-pandemic levels for AD and MS in summer 2020 and for asthma in spring 2021. COVID-19 led to an apparent decline in incidence for selected inflammatory and immunologic diseases, which was more pronounced for pediatric and senior populations. The observed decrease in incidence likely reflects delayed access to healthcare, resulting in unrecorded (but still occurring) diagnoses for those time periods. Future studies using data that encompass the pandemic period should exercise caution in the design of study and interpretation of incidence or prevalence data.

Idiopathic pulmonary fibrosis (IPF) is associated with cigarette smoking, yet the relationship between the tobacco-specific nitrosamine nicotine-derived nitrosamine ketone (NNK) and IPF-associated lung transcriptional remodeling remains incompletely understood. Here, we developed an exposure-informed computational framework integrating multi-database target prediction, lung single-cell and single-nucleus transcriptomic analysis, co-expression network analysis, bulk lung cohort projection, and exploratory structure-based modeling. Putative human protein targets of NNK were predicted from ChEMBL, PharmMapper, and SwissTargetPrediction, yielding 2,505 nonredundant targets. These targets were intersected with IPF-associated intramodular hub genes identified from cell type-specific weighted gene co-expression network analysis, defining a focused 42-gene ExposureA-core gene set. Projected ExposureA-core scores showed the clearest IPF-control differences in endothelial and epithelial pseudo-bulk profiles. Functional annotation of the training-derived epithelial ExposureA-core Top30 signature highlighted MAPK and p38 MAPK signaling, PI3K-AKT signaling, angiogenesis or vasculature regulation, cell-substrate adhesion, and membrane-, adhesion-, and cytoskeleton-related cellular components, suggesting remodeling- and adhesion-related epithelial transcriptional features in IPF. The fixed epithelial ExposureA-core Top30 signature remained detectable in independent bulk lung transcriptomic cohorts without gene re-selection, coefficient fitting, or score optimization, with exploratory ROC analyses showing apparent IPF-control separation in GSE110147 and GSE92592. Exploratory docking and 100-ns molecular dynamics simulations of selected epithelial Top30-encoded candidates showed that modeled ECE1-NNK, MMP7-NNK, and TGM2-NNK complexes reached dynamic equilibrium, with relatively stable RMSD, radius of gyration, solvent-accessible surface area, residue-level fluctuation, and low-energy conformational states, supporting their structural plausibility as candidate modeled complexes. Overall, this study defines a focused exposure-informed IPF-associated transcriptional framework and prioritizes epithelial remodeling-related candidate features for future experimental validation. These findings support hypothesis-generating computational prioritization rather than direct evidence that NNK drives IPF pathogenesis.

The sheep lung has long been used to model aspects of the human lung, both its normal development and pathological changes that occur in ovine models of lung disease. The similarities between the two species provide an opportunity to investigate phases of lung development that are not accessible for investigation in humans, for example later in gestation. Here we use single cell (sc) RNA-seq to investigate the developmental dynamics of the sheep proximal and distal lung from mid gestation (80 days) through late gestation (120 days) and term (147 days). We identify changes in cell identity and abundance between the time points that illustrate many key features of mesenchymal, endothelial, and epithelial differentiation. Lastly we compare the single cell profiles through development of wildtype (WT) sheep with those of animals of the same breed engineered to have a loss-of-function mutation in the cystic fibrosis transmembrane conductance regulator (CFTR) gene. Mutations in CFTR cause cystic fibrosis (CF) and the CFTR^-/- sheep exhibit many features of CF in humans. The results identify cellular signatures in the CFTR^-/- lung before birth that may facilitate the understanding of clinical features of CF in early postnatal life.

A woman in her early 50s presented with haemoptysis and cavitary pulmonary nodules. Initial testing showed a low-titre positive cryptococcal antigen (CrAg); however, repeat testing on two occasions was negative. Her cavitary nodules were ultimately attributed to an overlap systemic autoimmune rheumatic disease. She achieved complete clinical and radiological resolution with corticosteroid therapy. This case highlights the importance of recognising false-positive serum CrAg results.

The COVID-19 pandemic has contributed to more than 7 million deaths globally and has triggered a variety of postacute sequelae, now commonly referred to as long COVID, in millions more. Early efforts during the pandemic resulted in several therapies to mitigate the severity and mortality of acute COVID-19. However, despite effective therapies and accumulated immunity through vaccination and natural infection reducing disease severity, COVID-19 continues to contribute to hospitalizations and mortality. Long COVID encompasses several distinct yet overlapping clinical syndromes, and evidence suggests that these manifestations are mediated by numerous underlying mechanisms. There are currently no approved therapies for the treatment of long COVID, driven in part by its heterogeneity in presentation and etiology. This review will outline the current guidelines for treating acute COVID-19 and summarize information on the mechanistic rationale behind various published and ongoing clinical trials investigating potential long COVID therapeutic agents.

Advanced HIV infection is associated with profound immunosuppression, predisposing patients to opportunistic infections such as Pneumocystis jirovecii pneumonia (PJP) and Mycobacterium avium complex (MAC). PJP can cause severe respiratory disease, including acute respiratory distress syndrome (ARDS), while disseminated MAC may contribute to systemic illness and pulmonary complications. Concurrent infection with both pathogens is uncommon but may precipitate severe pulmonary failure. A man in his 40s presented with unintentional weight loss, fatigue, oral thrush, and progressive dyspnea. On arrival, oxygen saturation was 86% on room air, requiring high-flow nasal cannula. Laboratory evaluation revealed profound immunosuppression (CD4 7 cells/mm³, HIV RNA 123,000 copies/mL) and elevated β-D-glucan (>700 pg/mL). Chest CT demonstrated diffuse bilateral ground-glass opacities. He was initially treated empirically with broad-spectrum antibiotics (piperacillin-tazobactam and linezolid) and subsequently started on trimethoprim-sulfamethoxazole and corticosteroids for PJP. Despite supportive measures, the patient's respiratory status deteriorated, requiring intubation. Sputum cultures grew MAC, prompting initiation of azithromycin, rifampin, and ethambutol. The patient developed disseminated intravascular coagulation, acute tubular necrosis requiring daily hemodialysis, and septic shock requiring dual vasopressors. He was not a candidate for ECMO due to multi-organ failure in the context of advanced AIDS, and his prognosis remained guarded. This case highlights the rapid progression and complexity of opportunistic infections in advanced AIDS. Extensive diagnostic evaluation, early recognition of co-infections, and aggressive multidisciplinary management are essential, though outcomes may remain poor in patients with profound immunosuppression and multi-organ failure.

Anti-TNF and anti-IL-12/IL-23 are commonly used therapies for immune-mediated inflammatory diseases (IMIDs), including inflammatory bowel disease (IBD). Although several studies have shown intact T cell responses following 2 to 3 doses of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccines in biologics treated IMID patients, our group previously reported increased waning of T cell responses at 3-4 mos following the second vaccine dose in IMID patients compared to healthy controls, raising the possibility that a suboptimal initial T cell response could impact long term immunity. Here, to reduce patient heterogeneity, we focused only on IBD patients and further investigated T cell responses in vaccinated, untreated and biologics treated IBD patients compared to healthy controls. Following 1 vaccine dose, we observed a decreased frequency of Spike-reactive Th1 polarized cells and an increased frequency of Th2 cells in the IBD patients in general, relative to healthy controls. Additionally, IBD patients exhibited increased waning of Spike-specific cytokine T cell responses after 2 doses of vaccine. We also observed IBD-treatment specific effects. Spike-specific IL-2 secretion from anti-TNF or anti-IL-12/IL-23-treated patients' T cells was lower than from untreated patients following 1 dose of vaccine. However, single-cell RNA-sequencing of Spike-responsive T cells from anti-TNF and anti-IL-12/IL-23 treated IBD patients and healthy controls 2-4 wk after 2 or 3 vaccine doses revealed no major differences in T cell subsets, transcriptomes or TCR diversity. Thus, despite some evidence of impaired primary T cell responses, Spike-reactive T cells in patients treated with anti-TNF or anti-IL-12/IL-23 appear indistinguishable from healthy controls following a full vaccine course.

Comparative analysis of liver subpopulations of lymphocytes and cells of the system of mononuclear phagocytes on the material of autopsies in deaths from acute period of COVID-19, without its previous diseases and bacterial/mycotic superinfection, as well as from noninfection diseases in the distant future after the new coronavirus infection.

Study of morphological changes of the liver in 47 deaths from COVID-19, confirmed by a PCR test, and noninfection diseases within 40 to 300 days after a new coronavirus infection. The study did not include those who died with previous liver diseases and comorbid diseases accompanied by liver damage, and in the first two groups of observations - also with bacterial/mycotic superinfection, and after hepatotoxic therapy. 1 group consisted of 10 observations (average age - 75.2 years) with the exudative phase of diffuse alveolar damage (DAD), 2^nd group - 27 observations (average age - 71.7 years) with the proliferative or exudative-proliferative phases of DAD, 3d group - 10 observations (average age - 84.7 years), died from cardiovascular diseases in the period from 40 to 300 days after the transfer COVID-19. Imunohistochemical (IHC) reactions with antibodies to CD3, CD4, CD8, CD20, CD56 and CD68 were used with statistical analysis.

In portal tracts and perisinusoid spaces, the total number of CD3+, CD4+, CD8+, CD56+ and CD20+ lymphocytes and CD68+ cells are not higher in the acute period COVID-19, and in perisinusoid spaces are even less than in observations after a new coronavirus infection in patients died from cardiovascular diseases. The number of intraepithelial CD3+, CD4+, CD8+, CD56+ lymphocytes of the bile ducts of portal tracts was increased, which also infiltrate the walls of small vessels. Number of CD4+ lymphocytes in the stroma and liver parenchyma, ratio CD4+/CD8+ lymphocytes and proliferation of Kupfer cells are most increased in the exudative phase of DAD in COVID-19.

The study confirms that the morphological substrate COVID-19-associated liver damage may be ischemic hepatitis and COVID-19-associated cholangiopathy and microangiopathy give it a certain specificity. The revealed changes do not allow to exclude that the pathogenesis of liver damage can be also associated, including with other factors the direct action of SARS-CoV2 or immune disorders associated with COVID-19.

Cognitive changes after treatment of ruptured anterior communicating artery (AComA) aneurysms have been recognized for decades. Whether such deficits occur after elective treatment of unruptured aneurysms remains uncertain. A systematic search in MEDLINE (via PubMed and via Ovid), Embase, Scopus, Web of Science, CENTRAL and PsycINFO was conducted from inception to 31 August 2025, in accordance with PRISMA guidelines. Duplicate records were removed prior to screening. Studies were eligible if they included adult patients undergoing elective treatment of at least 1 unruptured AComA aneurysm, reported pre- and post-treatment neurocognitive testing across at least one cognitive subdomain, and differentiated outcomes from other aneurysm locations. Critical appraisal was performed using the Newcastle-Ottawa Scale, and certainty of evidence was assessed using the GRADE framework. Eight studies comprising 95 patients were included. In most studies, patients underwent surgical clipping (n = 82), with a minority treated endovascularly (n = 13). In five out of eight studies, patients who underwent elective treatment of an AComA aneurysm had worse cognitive outcomes than patients with aneurysms at non-AComA locations. Neurocognitive deficits may be detected in a substantial proportion of patients undergoing elective treatment of unruptured AComA aneurysms when sensitive neuropsychological assessment is applied. However, the current evidence base is limited by small sample sizes, heterogeneity in neuropsychological assessment, and a predominance of surgically treated cases.