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Recruited Monocyte-Derived Macrophages Drive T Cell Inflammation in Immune Checkpoint Inhibitor-Mediated Pneumonitis.3 weeks agoBackground: Immune checkpoint inhibitor-mediated pneumonitis (CIP) constitutes a major toxicity that limits the clinical application of cancer immunotherapy, whereas its underlying mechanisms remain incompletely understood. Current management relies on nonspecific immunosuppressants, lacking precision therapies. Although single-cell RNA sequencing (scRNA-seq) of bronchoalveolar lavage fluid (BALF) has implicated T cell activation and inflammatory myeloid responses in CIP pathogenesis, critical gaps persist regarding interstitial lung immunity and mechanisms governing monocyte/macrophage-T cell co-enrichment and crosstalk. We aimed to delineate the lung immune circuits that drive CIP and to identify targetable monocyte/macrophage-T cell pathways that could be leveraged for precision intervention. Methods: To elucidate CIP pathogenesis, we performed integrated scRNA-seq analysis of BALF from CIP+ and CIP- patients with validation in a prospective cohort using flow cytometry, enzyme-linked immunosorbent assay, Western blotting, and quantitative polymerase chain reaction. Mechanistic studies were performed using an established tumor-bearing forkhead box P3-diphtheria toxin receptor-green fluorescent protein (Foxp3-DTR-GFP) mouse model of programmed death-1 inhibitor-induced CIP via micro-computed tomography, histopathology, scRNA-seq, flow cytometry, multiplex immunofluorescence, Western blotting, Transwell migration assays, and pharmacologic interventions. Results: In CIP+ patient BALF and mouse lung tissues, CD8+ T cells expressing cytotoxic effectors and C-X-C chemokine receptor 3 (CXCR3) expanded concomitantly with distinct C-C chemokine receptor 2 (CCR2)+ monocyte-derived macrophages (MoMΦ) exhibiting a highly inflammatory phenotype, while tissue-resident macrophages were markedly reduced. Mouse models revealed that expanded CCR2+ MoMΦ originating from circulation replenished the depleted niche of lung-resident interstitial macrophages. Mechanistically, integrated in silico prediction and experimental validation demonstrated that CCR2+ MoMΦ recruited CD8+ T cells via the C-X-C motif chemokine ligand 9/10 (CXCL9/10)-CXCR3 axis. Conversely, CD8+ T cells drove CCR2+ MoMΦ expansion and pro-inflammatory phenotype via the interferon-γ (IFN-γ) axis, suggesting the existence of a positive feedback loop between these cell types. Pharmacological targeting of CCR2/CCR5 or CXCR3 signaling attenuated pneumonitis, reduced pulmonary CCR2+ MoMΦ infiltration, diminished pathogenic T cell activation and cytotoxicity, and improved survival without compromising antitumor immunity. Conclusions: Our findings establish CCR2+ MoMΦ and the IFN-γ-CXCL9/10-CXCR3 axis as core drivers of CIP pathogenesis and validate their therapeutic targeting potential. This work provides a scientific foundation for developing CIP-specific prevention and treatment strategies.Chronic respiratory diseaseCare/Management
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Probiotic mediated modulation of neonatal health: a meta-analysis of prematurity-related morbidity, jaundice, and respiratory distress.3 weeks agoPrematurity remains a major contributor to neonatal morbidity and mortality worldwide, with neonatal jaundice and respiratory distress syndrome (RDS) representing two of the most common complications associated with immature hepatic and pulmonary development. Increasing evidence suggests that probiotic supplementation may improve neonatal outcomes through modulation of the gut microbiome, gut-liver axis, and gut-lung axis; however, published findings remain inconsistent. The meta-analysis evaluated the effects of probiotic supplementation on prematurity-related morbidity, with particular emphasis on neonatal jaundice and RDS.
The study was conducted according to PRISMA 2020 guidelines, and a comprehensive literature search of PubMed, Scopus, Web of Science, and the Cochrane Library identified 18 eligible studies comprising 2,587 preterm infants. Methodological quality was assessed using the Cochrane Risk of Bias 2 tool and Newcastle-Ottawa Scale, and pooled effect estimates were calculated using random-effects models.
Probiotic supplementation significantly reduced the incidence of neonatal jaundice (RR = 0.72, 95% CI: 0.61-0.84; p < 0.001), peak total serum bilirubin levels (MD = -1.84 mg/dL, 95% CI: -2.47 to -1.21), and phototherapy requirements (RR = 0.68, 95% CI: 0.55-0.82; p < 0.001). The incidence of RDS was significantly reduced (RR = 0.79, 95% CI: 0.66-0.95; p = 0.012), accompanied by a shorter duration of respiratory support (MD = -1.9 days, 95% CI: -2.8 to -1.0). Moderate heterogeneity was observed across pooled analyses (I² = 42-57%). Exploratory meta-regression suggested that probiotic formulation, early initiation (<72 h), and gestational age contributed to between-study variability.
Probiotic supplementation was associated with favorable clinical outcomes in preterm infants. The moderate between-study heterogeneity, variability in probiotic strains, formulations, dosages, and treatment protocols, together with limited long-term safety data, warrant cautious interpretation. Future adequately powered multicenter randomized controlled trials, standardized probiotic interventions, individual-patient-data meta-analyses, and long-term follow-up studies are required before routine clinical implementation and standardized probiotic treatment recommendations can be established.Chronic respiratory diseaseCare/Management -
Severe co-infection with influenza A virus H3N2 and community-acquired methicillin-susceptible Staphylococcus aureus in a child presenting with septic shock, acute respiratory distress syndrome, and necrotizing pneumonia: a rare case report.3 weeks agoInfluenza co-infection with Staphylococcus aureus (S. aureus) can cause rapidly fatal necrotizing pneumonia, septic shock, and acute respiratory distress syndrome (ARDS) in children. Although methicillin-resistant S. aureus is often highlighted, community-acquired methicillin-susceptible S. aureus (CA-MSSA) can also produce equally severe disease.
We report an 8-year-4-month-old male with influenza A (H3N2) who developed septic shock and refractory hypoxemia, requiring immediate intubation. Due to persisting respiratory failure despite maximal ventilation, veno-venous extracorporeal membrane oxygenation (VV-ECMO) was initiated on day 1. Metagenomic next-generation sequencing identified S. aureus as the dominant pathogen, and bronchoalveolar lavage fluid culture later confirmed MSSA. After vancomycin failed clinically, the regimen was switched to linezolid. However, on day 15 of linezolid therapy, the patient developed severe linezolid-induced lactic acidosis (LILA), which resolved within 3 days of stopping the drug. The clinical course was further complicated by pneumothorax and multidrug-resistant organism superinfections. After 54 days of intensive care, the patient was discharged in good condition.
This case underscores that during influenza seasons, early empirical anti-staphylococcal therapy should be considered in children with rapidly progressive pneumonia and shock, even when CA-MSSA is suspected. Additionally, routine lactate monitoring is critical during linezolid therapy to enable prompt recognition and management of life-threatening LILA.Chronic respiratory diseaseCare/Management -
Critical role for the TGF-β1/mTORC1 signaling axis in defining the transcriptional identity of CTHRC1+ pathologic fibroblasts.3 weeks agoFibrosis, marked by excess extracellular matrix (ECM) deposition, is the end stage of many diseases. Single-cell studies have highlighted the emergence of disease-specific fibroblast populations, including a high collagen-synthesizing CTHRC1+ subpopulation. The profibrotic cytokine TGF-β1 promotes fibrogenesis via cooperation between Smad and mTORC1/4E-BP1 signaling axes. Using CRISPR-Cas9 gene editing, we report that more than one-third of TGF-β1-regulated matrisome genes are under mTORC1 control. Mapping the transcriptome of TGF-β1-stimulated fibroblasts revealed similarity to CTHRC1+ fibroblasts identified in idiopathic pulmonary fibrosis (IPF). This overlap is lost when mTORC1 is disabled. Using the selective mTORC1 inhibitor RMC-5552, we confirm a causal role for mTORC1 in promoting the acquisition of the collagen-high, CTHRC1+ phenotype in response to TGF-β1 stimulation in fibroblasts derived from patients with either IPF or lung adenocarcinoma. We conclude that mTORC1 plays a key role in shaping the transcriptional identity of these fibroblasts, with implications for therapeutic inhibition of mTORC1 in fibrosis and cancer.Chronic respiratory diseasePolicy
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Environmental Adaptability of Influenza A(H9N2) Virus in the Process of Genetic Evolution.3 weeks agoUnderstanding the transmission routes of avian influenza viruses (AIVs) is critical for outbreak control. Beyond direct contact and aerosol transmission, indirect transmission via contaminated environmental surfaces contributes to exposure risk, particularly in live poultry markets (LPMs). Although previous studies have examined the environmental persistence of individual AIV strains, systematic comparisons among genetically related viruses remain scarce. H9N2, designated by the WHO as a potential "Pathogen X," is of particular concern. Here, we assessed the environmental persistence and indirect transmission potential of four genetically related H9N2 AIVs originating from the same LPM-associated epidemiological context: one human isolate (H19) and three LPM environmental isolates (E01, E02, E03). All viruses exhibited temperature-dependent infectivity decay on four surface materials. Notably, H19 and E01 demonstrated prolonged environmental persistence compared with E02 and E03 under multiple conditions. Moreover, smooth, non-porous surfaces (plastic, glass, stainless steel) generally supported longer viral survival than porous non-woven fabric. In a guinea pig model, H19 and E01 led to detectable indirect transmission, whereas E02 and E03 did not. Comparative sequence analysis revealed differences at NP-346 and PB2-18 between these two phenotypic groups, although the functional relevance of these substitutions remains to be determined. Collectively, these findings reveal that environmental persistence and indirect transmission potential can vary markedly among genetically related LPM-associated H9N2 AIVs, supporting the integration of environmental adaptability into routine risk assessment frameworks.Chronic respiratory diseaseAdvocacy
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Pandemic research in a small island society-a narrative review of research contributions during the SARS-CoV-2 pandemic in the Faroe Islands.3 weeks agoSmall and geographically isolated societies face distinct challenges during a pandemic but may also possess advantages. This narrative literature review presents epidemiological, immunological and psychological studies conducted in the Faroe Islands during the SARS-CoV-2 pandemic, examining its effects on individuals in the Faroe Islands. The COVID-19 pandemic hit the Faroe Islands early in March 2020. With only around 55,000 inhabitants, the Faroe Islands' isolated, well-documented population enabled extensive epidemiological research and close monitoring of infection patterns. This resulted in studies on transmission, immunity, mental health and long COVID. Overall, the Faroese studies demonstrate how small, cohesive societies with robust infrastructure can conduct high-quality research during a crisis, contributing to both local and global knowledge.Chronic respiratory diseaseMental HealthAdvocacy
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Addressing risk factors for hypertensive disorders in pregnancy: A case study of a quality improvement program in two states in Nigeria.3 weeks agoHypertensive disorders of pregnancy (HDP) including chronic hypertension, gestational hypertension preeclampsia and eclampsia are a leading cause of maternal and perinatal mortality in Nigeria and globally and increase the risk for future cardiovascular disease among women of reproductive age (WRA). The quality improvement program was implemented from 2019 through 2022 in the Federal Capital Territory (FCT) and Lagos State of Nigeria to improve early detection and management of HDP and risk factors (anemia, diabetes) at key maternal and reproductive healthcare touch points. A facility-based assessment evaluated provider knowledge and practices related to antenatal care diagnosis and management of HDP and risk factors in pregnant women in 20 facilities. From 2019 to 2022 the program implemented a package of interventions in 40 public and private health facilities to improve prevention, early detection, and management of HDP and risk factors among WRA during antenatal care (ANC), postnatal care (PNC), and family planning (FP) visits. ANC assessment results demonstrated important gaps in ANC providers' knowledge, self-reported confidence and observed adherence with HDP and risk factor management best practices. Among 93,384 ANC visits across program facilities the median proportion of women who had a blood pressure, anemia and diabetes check increased from 44% to 89%, 48% to 91% and 32% to 87%, respectively, from baseline (October 2019-March 2020) to the program final 6 months (July-December 2022). From January 2021 to December 2022, the median proportion of 57,658 PNC visits with a documented BP check increased from 81% to 90% and the median proportion of 105,237 FP visits with a BP check increased from 73% to 98% from an initial baseline period (January- June 2021) to the last 6 months of program implementation (July-December 2022). In a program setting with a high burden of maternal mortality and morbidity due to hypertensive disorders and a high prevalence of cardiovascular disease, improving identification and management of HDP and risk factors at key health care touch points for women of reproductive age has the potential to reduce HDP morbidity and mortality and future premature cardiovascular mortality among women of reproductive age.Cardiovascular diseasesAccessCare/ManagementAdvocacy
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Validation and Reliability Assessment of the Indonesian Version of the Self-Care Behaviour Instrument for Haemodialysis With Arteriovenous Fistula.3 weeks agoArteriovenous fistula is a vascular access commonly used for long-term haemodialysis because of its durability and lower complication rate. Adequate self-care is essential, as poor self-care may lead to thrombosis, infection, and early access failure. Currently, Indonesia lacks a validated instrument to measure specific self-care behaviours.
This study aims to adapt and translate the Assessment of Self-Care Behaviours with Arteriovenous Fistula instrument into Indonesian and to evaluate its psychometric properties among patients receiving haemodialysis in Indonesia.
Cross-sectional validation study.
This study included 160 patients undergoing haemodialysis using an arteriovenous fistula.
The cross-cultural adaptation process followed internationally recognised guidelines. Content validity was evaluated by experts using the Item Content Validity Index and Scale Content Validity Index. Construct validity was examined using Exploratory Factor Analysis. Reliability testing was conducted using Cronbach's α coefficient.
All 16 items demonstrated satisfactory content validity. The Kaiser-Meyer-Olkin value was 0.815, and Bartlett's test was significant (p < 0.001), confirming data suitability for factor analysis. Exploratory factor analysis identified a two-factor structure explaining 55.04% of the total variance, representing management of signs and symptoms and prevention of complications. The overall scale showed excellent internal consistency (α = 0.902), with α values of 0.902 and 0.833 for Factors 1 and 2, respectively.
The Indonesian version of the Assessment of Self-Care Behaviours with Arteriovenous Fistula scale is valid and reliable in assessing self-care behaviours among patients receiving haemodialysis with arteriovenous fistula in Indonesia.Cardiovascular diseasesAccessCare/ManagementAdvocacy -
[Development and Validation of a Nomogram Prediction Model for Pulmonary Infection in Cerebral Infarction Patients During the Recovery Phase After Acupuncture Treatment].3 weeks agoTo analyze the risk factors for pulmonary infection in convalescent patients with cerebral infarction under acupuncture and moxibustion intervention, and to develop a nomogram model.
According to a modeling-to- verification set ratio of 7∶3, 350 patients with cerebral infarction treated in the hospital from January 2022 to January 2024 were selected as the modeling set. At the same time, 150 patients with cerebral infarction admitted from February 2024 to December 2024 were selected as the verification set. General patient information, laboratory indicators, and acupuncture intervention variables were collected. After screening variables using LASSO regression in the modeling set, multivariate logistic regression was performed. Based on the results of the multivariate regression, a nomogram prediction model was established, and the models were evaluated in the modeling and validation set, respectively.
The incidence of pulmonary infection in patients with cerebral infarction during convalescence was 26.20%(131/500), including 95 patients in the model group. A total of 147 pathogen strains were detected, mainly Gram- negative bacteria. Modeling concentration, LASSO regression, and multivariate stepwise logistic regression were used to identify factors influencing pulmonary infection: increased age (OR = 1.043, 95%CI: 1.010-1.077), higher Eating Assessment Tool 10 (EAT-10) score (OR = 1.249, 95%CI: 1.125-1.387), invasive procedures (OR = 2.715, 95%CI: 1.340-5.501), higher National Institutes of Health Stroke Scale (NIHSS) score (OR = 2.477, 95%CI: 1.951-3.144), lower albumin (OR = 0.856, 95%CI: 0.786-0.931), lower prealbumin (OR = 0.992, 95%CI: 0.987-0.997), needle retention time of 30 min (OR = 2.439,95%CI: 1.146-5.191), acupuncture course less than 14 d (OR = 2.463,95%CI: 1.157-5.243), and initiation of intervention acupuncture treatment more than >3 d after onset (OR = 2.660, 95%CI: 1.190-5.942). Based on these factors, a nomogram model was constructed, with areas under the curve (AUC) of 0.916 (95%CI: 0.877-0.954) and 0.923 (95%CI: 0.874-0.973). The calibration curve showed that the predicted probabilities of the model were in close agreement with the observed probabilities, and its application could yield positive net clinical benefits.
The nomogram model constructed used Lasso-logistic regression can identify the risk of pulmonary infection in patients with cerebral infarction during convalescence after acupuncture treatment. Quantifying risk factors can guide patients in optimizing acupuncture treatment plans, achieving precise intervention, and reducing the risk of infection.Cardiovascular diseasesAccessCare/ManagementAdvocacy -
[Independent Risk Factors for Venous Thromboembolism After Gynecological Surgery and the Predictive Value of Postoperative D-Dimer].3 weeks agoTo investigate the independent risk factors for venous thromboembolism (VTE) after gynecological surgery, evaluate the predictive performance of postoperative D-dimer levels for VTE, and inform the development of individualized anticoagulation strategies.
Perioperative data were collected from 307 female patients who underwent gynecological surgeries at West China Shangjin Nanfu Hospital, Sichuan University between March 2020 and March 2022. The inclusion criteria were a Caprini score ≥ 3 and the absence of any VTE prophylaxis. The data collected included age, body mass index (BMI), menopause, comorbidities (e.g., hypertension), preoperative and postoperative coagulation parameters (prothrombin time, activated partial thromboplastin time, fibrinogen, D-dimer, etc.), the surgical approach, anesthesia duration, surgery duration, American Society of Anesthesiologists (ASA) physical status classification, and postoperative VTE occurrence confirmed by imaging examinations. Patients were divided into VTE and non-VTE groups according to postoperative imaging findings. Univariate analysis was performed to compare differences between groups. Binary logistic regression was performed to identify independent risk factors. The receiver operating characteristic (ROC) curve was plotted, and the area under the curve (AUC), sensitivity, specificity, and Youden index were calculated to evaluate the predictive performance of D-dimer levels.
Among the 307 patients, 42 (13.68%) developed postoperative VTE, including 30 cases (9.77%) of deep vein thrombosis (DVT) and 12 cases (3.91%) of pulmonary embolism (PE). Multivariable logistic regression analysis showed that independent risk factors for postoperative VTE included age (odds ratio [OR] = 1.122 per year, 95% CI: 1.070-1.176), increased BMI (OR = 1.180, 95% CI: 1.031-1.351), menopause (OR = 13.753, 95% CI: 3.692-51.229), hypertension (OR = 3.951, 95% CI: 1.837-8.498), prolonged surgery duration (OR = 1.047 per minute, 95% CI: 1.013-1.082), prolonged anesthesia duration (OR = 1.007 per minute, 95% CI: 1.002-1.011), higher ASA classification (OR = 8.122, 95% CI: 2.973-22.184), and elevated postoperative D-dimer levels (OR = 1.177 per mg/L, 95% CI: 1.029-1.346). Although the Caprini score was significantly higher in the VTE group than that in the non-VTE group (4.57 ± 1.21 vs. 3.64 ± 1.11, P < 0.001), binary logistic regression analysis revealed no statistically significant association (P = 0.877). A postoperative D-dimer level = 1.50 mg/L was the optimal threshold for diagnosing VTE, yielding a sensitivity of 54.76%, specificity of 73.58%. A preoperative-to-postoperative D-dimer change = 2.50 mg/L showed a sensitivity of 26.19%, specificity of 94.72%.
Increased age, higher BMI, menopause, hypertension, prolonged surgery duration and anesthesia duration, and higher ASA classification are independent risk factors for VTE after gynecological surgery. A postoperative D-dimer level ≥ 1.50 mg/L and a preoperative-to-postoperative D-dimer change ≥ 2.50 mg/L may serve as practical indicators for VTE screening and early risk identification and should be incorporated into routine postoperative monitoring. The Caprini score demonstrated limited predictive value for VTE risk in this gynecological patient cohort. Therefore, a risk assessment model tailored to patients undergoing gynecological surgery should be developed by incorporating these risk factors.Cardiovascular diseasesAccessAdvocacy