Search

We describe two cases of secondary prevention subcutaneous implantable cardioverter defibrillator (S‐ICD) implantation and subsequent S‐ICD electrode displacement which initially went undetected. One presentation was a result of a coincidental chest x‐ray for respiratory exacerbation and another with an untreated episode highlighted via remote monitoring, both patients were booked to clinic for further investigation. Our findings highlighted had there been a comparison of the existing subcutaneous electrogram (S‐ECG) to captured S‐ECGs at time of implant the electrode displacement would have been detected beforehand. This underpins the importance of introducing the simple management strategy into routine follow‐up. [ABSTRACT FROM AUTHOR]

The study examines the safety of performing simultaneous surgery for pituitary neoplasms and rhinosinusitis. Results show that there is no significant increase in nasal or intracranial complications when combining transsphenoidal surgery with endoscopic sinus surgery. The study suggests that simultaneous surgery for these conditions can be considered safe and feasible. Additionally, the research highlights the importance of preoperative antibiotic treatment and the lack of significant association between sinusitis severity and complication rates. [Extracted from the article]

Associations between air pollution and the acute exacerbations (AEs) of COPD have been established primarily in time-series studies in which exposure and health data were at the aggregate level, limiting the identification of susceptible populations. Are air pollutants associated with the onset of AEs of COPD in China? Who is more susceptible to the effects of air pollutants? Data regarding AEs of COPD were obtained from the Acute Exacerbation of Chronic Obstructive Pulmonary Disease Registry (ACURE) study, and air pollution data were assigned to individuals based on their residential address. We adopted a time-stratified case-crossover study design combined with conditional logistic regression models to estimate the associations between six air pollutants and AEs of COPD. Stratified analyses were performed by individual characteristics, disease severity, COPD types, and the season of exacerbations. A total of 5,746 patients were included. At a 2-day lag, for each interquartile range increase in fine particulate matter and inhalable particulate matter concentrations, ORs for AEs of COPD were 1.054 (95% CI, 1.012-1.097) and 1.050 (95% CI, 1.009-1.092), respectively. The associations were more pronounced in participants who were younger than 65 years, who had experienced at least one severe AE of COPD in the past year, who had received a diagnosis of COPD between 20 and 50 years of age, and who had experienced AEs of COPD in the cool seasons. By contrast, significant associations for nitrogen dioxide, sulfur dioxide, and carbon monoxide lost significance when excluding patients collected before 2020 or with greater distance from the monitoring station, and no significant association was observed for ozone. This study provides robust evidence that short-term exposure to fine particulate matter and inhalable particulate matter was associated with higher odds of AEs of COPD onset. Individuals who are young, have severe COPD, or whose first diagnosis of COPD was made when they were between 20 and 50 years of age and experience an exacerbation during the cooler seasons may be particularly susceptible. ClinicalTrials.gov; No.: NCT2657525; URL: www.clinicaltrials.gov [ABSTRACT FROM AUTHOR]

Objective: To investigate the role of 14-3-3β in acute asthma exacerbations in children and analyze the risk factors for asthma exacerbations. Methods: This study recruited 101 children with acute asthma exacerbations, 101 children with stable asthma, and 65 healthy children. Serum 14-3-3β was compared among the three groups. Factors such as asthma family history, skin prick test, serum-specific IgE test, coinfections, and clinical indicators (FeNO, FEV1, white blood cells, eosinophils, and serum IgE level) were compared between the asthma groups. Risk factors associated with acute asthma exacerbations were identified using multivariate logistic regression models. ROC curve was drawn to determine the diagnostic sensitivity and specificity of 14-3-3β. Results: Serum 14-3-3β was significantly greater in the acute asthma group than in the stable asthma and control groups. Serum 14-3-3β was higher in severe acute asthma group than in mild-moderate asthma group. There were no significant differences in serum 14-3-3β levels between stable asthma and control groups (p >.05). Multivariate logistic regression analysis revealed that serum 14-3-3β level, FeNO, coinfection, and FEV1 z-score significantly increased the odds of acute asthma exacerbations in children. The optimal 14-3-3β cutoff value (39.79 ng/mL), had a sensitivity of 69.3% and specificity of 94.1% for predicting acute asthma exacerbations. Conclusions: 14-3-3β is elevated in children with acute exacerbations of asthma, and increases with exacerbation severity. 14-3-3β, FeNO, FEV1, and coinfection could be independent risk factors for predicting asthma exacerbations. The optimal 14-3-3β cutoff value for predicting asthma exacerbations was 39.79 ng/mL. [ABSTRACT FROM AUTHOR]

Aim: To explore experiences of patients affiliated to a cross‐sectorial outgoing lung team. Background: The outgoing lung team consisted of respiratory nurses from the hospital and community nurses. The lung team offered 24/7 help to patients with advanced chronic obstructive pulmonary disease (COPD) through visits and/or treatment in the patients' home. Affiliation to the lung team reduced both hospitalizations and length of hospital stay due to acute exacerbation of COPD. However, based on questionnaires on health‐related quality of life, no significant differences were found between patients affiliated to the lung team and patients receiving usual care. Design: A qualitative interview study. Methods: In total, 16 patients, aged 61–88 years were interviewed between February 2019 and July 2021. They had been affiliated to the outgoing lung team for 1–3 years. Semi‐structured interviews were conducted in the patients' home and audio‐recorded after informed consent was obtained. The interviews were transcribed verbatim and analysed, inspired by systematic text condensation by Malterud. Findings: Four themes emerged from the analysis: (1) feeling safe, (2) improvements in living with COPD, (3) avoiding hospitalization and (4) satisfied with staying at home. Conclusion: Affiliation to the cross‐sectorial outgoing lung team gave the patients peace of mind and improved their ability to live with advanced COPD. The patients preferred contacting the lung team because they could stay at home and receive treatment, and thus avoid hospitalization. Impact: The findings from this study support that municipalities should consider implementing an outgoing lung team, as it has the potential to bring several benefits, including improving patient self‐management. Reporting Method: The manuscript adhered to Consolidated criteria for reporting qualitative research (COREQ) guideline. Patient or Public Contribution: Patients were interviewed. Additionally, no patient or public contributed to the design or conduction of the study, analysis, or interpretation of the data. [ABSTRACT FROM AUTHOR]

• Allergen challenge impacts resting state functional connectivity in asthma. • Salience network connectivity declines in those with elevated depressive symptoms. • Salience network connectivity is maintained in those with low depressive symptoms. • Maintenance of SN connectivity during inflammation may index resilience. Inflammation is an established contributor to the pathophysiology of depression and the prevalence of depression in those with chronic inflammatory disease is two- to four-fold higher than the general population. Yet little is known about the neurobiological changes that confer depression or resilience to depression, that occur when episodes of heightened inflammation are frequent or span many years. We used an innovative combination of longitudinal resting state functional magnetic resonance imaging coupled to segmental bronchial provocation with allergen (SBP-Ag) to assess changes in resting state functional connectivity (rsFC) of the salience network (SN) caused by an acute inflammatory exacerbation in twenty-six adults (15 female) with asthma and varying levels of depressive symptoms. Eosinophils measured in bronchoalveolar lavage fluid and blood provided an index of allergic inflammation and the Beck Depression Inventory provided an index of depressive symptoms. We found that in those with the highest symptoms of depression at baseline, SN rsFC declined most from pre- to post-SBP-Ag in the context of a robust eosinophilic response to challenge, but in those with low depressive symptoms SN rsFC was maintained or increased, even in those with the most pronounced SBP-Ag response. Thus, the maintenance of SN rsFC during inflammation may be a biomarker of resilience to depression, perhaps via more effective orchestration of large-scale brain network dynamics by the SN. These findings advance our understanding of the functional role of the SN during inflammation and inform treatment recommendations for those with comorbid inflammatory disease and depression. [ABSTRACT FROM AUTHOR]

BACKGROUND: Home noninvasive ventilation (NIV) may improve chronic hypercarbia in COPD and patient-important outcomes. The efficacy of home high-flow nasal cannula (HFNC) as an alternative is unclear. METHODS: We searched MEDLINE, Embase, Cochrane CENTRAL, Scopus, and ClinicalTrials.gov for randomized trials of subjects from inception to March 31, 2023, and updated the search on July 14, 2023. We performed a frequentist network meta-analysis and assessed the certainty of the evidence using the Grading of Recommendations Assessment, Development, and Evaluation approach. We analyzed randomized controlled trials (RCTs) comparing NIV, HFNC, or standard care in adult subjects with COPD with chronic hypercapnic respiratory failure. Outcomes included mortality, COPD exacerbations, hospitalizations, and quality of life (St George Respiratory Questionnaire [SGRQ]). RESULTS: We analyzed 24 RCTs (1,850 subjects). We found that NIV may reduce the risk of death compared to standard care (relative risk 0.82 [95% CI 0.66-1.00]) and probably reduces exacerbations (relative risk 0.71 [95% CI 0.58-0.87]). HFNC probably reduces exacerbations compared to standard care (relative risk 0.77 [0.68-0.88]), but its effect on mortality is uncertain (relative risk 1.20 [95% CI 0.63-2.28]). HFNC probably improves SGRQ scores (mean difference -7.01 [95% CI -12.27 to -1.77]) and may reduce hospitalizations (relative risk 0.87 [0.69-1.09]) compared to standard care. No significant difference was observed between HFNC and NIV in reducing exacerbations. CONCLUSIONS: Both NIV and HFNC reduce exacerbation risks in subjects with COPD compared to standard care. HFNC may offer advantages in improving quality of life. [ABSTRACT FROM AUTHOR]

Background Digital health interventions (DHIs) have significant potential to upscale treatment access to people experiencing psychosis but raise questions around patient safety. Adverse event (AE) monitoring is used to identify, record, and manage safety issues in clinical trials, but little is known about the specific content and context contained within extant AE reports. This study aimed to assess current AE reporting in DHIs. Study Design A systematic literature search was conducted by the iCharts network (representing academic, clinical, and experts by experience) to identify trials of DHIs in psychosis. Authors were invited to share AE reports recorded in their trials. A content analysis was conducted on the shared reports. Study Results We identified 593 AE reports from 18 DHI evaluations, yielding 19 codes. Only 29 AEs (4.9% of total) were preidentified by those who shared AEs as being related to the intervention or trial procedures. While overall results support the safety of DHIs, DHIs were linked to mood problems and psychosis exacerbation in a few cases. Additionally, 27% of studies did not report information on relatedness for all or at least some AEs; 9.6% of AE reports were coded as unclear because it could not be determined what had happened to participants. Conclusions The results support the safety of DHIs, but AEs must be routinely monitored and evaluated according to best practice. Individual-level analyses of AEs have merit to understand safety in this emerging field. Recommendations for best practice reporting in future studies are provided. [ABSTRACT FROM AUTHOR]

Background: The inflammatory response is the main pathophysiological basis of acute exacerbations of chronic obstructive pulmonary disease (AECOPD) and is a key factor leading to frequent exacerbations and disease progression. Suppressing the inflammatory response can improve pulmonary function, prognosis, and quality of life in AECOPD patients. Purpose: To evaluate the effect of Qingjin Huatan decoction (QHD) on pulmonary function and inflammatory mediators in AECOPD patients. Methods: Randomized controlled trials (RCTs) on the treatment of AECOPD with QHD were retrieved from eight Chinese and English electronic databases up to 31 May 2024. The quality of the studies was assessed using the Cochrane Risk of Bias Tool and the modified Jadad scale. Statistical analysis, sensitivity analysis, and publication bias assessment were performed using Stata 17.0 software. Results: A total of 40 RCTs involving 3,475 AECOPD patients were included. Compared to conventional treatment, QHD significantly improved pulmonary function, with increases in FEV1 (MD = 0.30, 95% CI: 0.26 to 0.34, p = 0.000), FVC (MD = 0.34, 95% CI: 0.27 to 0.41, p = 0.000), FEV1/FVC (MD = 6.07, 95% CI: 5.55 to 6.58, p = 0.000), and PaO2 (MD = 7.20, 95% CI: 4.94 to 9.47, p = 0.000), and a decrease in PaCO2 (MD = -5.37, 95% CI: 7.99 to -2.74, p = 0.000). QHD also significantly suppressed the expression of inflammatory mediators, including TNF-a (MD = -10.87, 95% CI: 12.51 to -9.23, p = 0.000), IL-1ß (MD = -13.63, 95% CI: -16.31 to -10.95, p = 0.000), IL-6 (MD = -7.58, 95% CI: -10.10 to -5.06, p = 0.000), IL-8 (MD = -9.45, 95% CI: -12.05 to -6.85, p = 0.000), CRP (MD = -5.62, 95% CI: -6.60 to -4.65, p = 0.000), and PCT (MD = -0.84, 95% CI: -1.07 to -0.62, p = 0.000). Additionally, QHD improved clinical efficacy (RR = 4.16, 95% CI: 3.26 to 5.30, p = 0.000) without increasing the incidence of adverse reactions (RR = 1.04, 95% CI: 0.68 to 1.61, p = 0.000). Conclusion: Existing evidence suggests that QHD can significantly improve pulmonary function, suppress the expression of inflammatory mediators, and enhance clinical efficacy in AECOPD patients, with a good safety profile. Given the limitations of this study, more high-quality studies are needed to provide reliable evidence. [ABSTRACT FROM AUTHOR]

Background: Chronic obstructive pulmonary disease (COPD) has become one of the major death-related causes. Chronic pulmonary heart disease (CPHD) is an adverse complication of COPD causing poor prognosis of patients. This study evaluated the role of lncRNA XIST in COPD and CPHD aiming to identify a potential biomarker for the screening and prediction of COPD. Methods: The study enrolled 127 COPD patients, including 73 patients occurred CPHD with 76 healthy individuals as the control group. The expression of XIST was evaluated by PCR and compared between COPD patients with different severity, grades, and complications. The diagnostic and prognostic values of XIST in COPD and CPHD were assessed by ROC and Kaplan-Meier analyses. Results: Significant upregulation of XIST was observed in the serum of COPD patients relative to healthy individuals, which distinguished COPD patients and showed a correlation with the respiratory and pulmonary function of COPD patients. COPD patients with acute exacerbations and CPHD showed a higher expression level. Increasing serum XIST discriminated COPD patients combined CPHD and positively correlated with right ventricular hypertrophy and pulmonary hypertension. Higher serum XIST levels could indicate the adverse 3-year prognosis of COPD patients, especially for COPD patients combined with CPHD. Conclusion: Upregulated XIST served as a biomarker for screening COPD and predicting adverse prognosis of COPD and COPD patients with CPHD. [ABSTRACT FROM AUTHOR]

Chronic obstructive pulmonary disease (COPD) is a common, costly, and morbid condition. Pulmonary rehabilitation, close monitoring, and early intervention during acute exacerbations of symptoms represent a comprehensive approach to improve outcomes, but the optimal means of delivering these services is uncertain. Logistical, financial, and social barriers to providing healthcare through face-to-face encounters, paired with recent developments in technology, have stimulated interest in exploring alternative models of care. The Healthy at Home study seeks to determine the feasibility of a multimodal, digitally enhanced intervention provided to participants with COPD longitudinally over 6 months. This paper details the recruitment, methods, and analysis plan for the study, which is recruiting 100 participants in its pilot phase. Participants were provided with several integrated services including a smartwatch to track physiological data, a study app to track symptoms and study instruments, access to a mobile integrated health program for acute clinical needs, and a virtual comprehensive pulmonary support service. Participants shared physiologic, demographic, and symptom reports, electronic health records, and claims data with the study team, facilitating a better understanding of their symptoms and potential care needs longitudinally. The Healthy at Home study seeks to develop a comprehensive digital phenotype of COPD by tracking and responding to multiple indices of disease behavior and facilitating early and nuanced responses to changes in participants' health status. This study is registered at Clinicaltrials.gov (NCT06000696). [ABSTRACT FROM AUTHOR]

Background Aim Methods Results Conclusions Air pollutants, such as diesel exhaust particles (DEPs), induce respiratory disease exacerbation with neutrophilic infiltration. Progranulin (PGRN), an epithelial cell and macrophage‐derived secretory protein, is associated with neutrophilic inflammation. PGRN is digested into various derivatives at inflammatory sites and is involved in several inflammatory processes. PGRN and its derivatives likely regulate responses to DEP exposure in allergic airway inflammation.To investigate the role of PGRN and its derivatives in the regulation of responses to DEP exposure in allergic airway inflammation.A murine model of allergic airway inflammation was generated in PGRN‐deficient mice, and they were simultaneously exposed to DEP followed by intranasal administration of full‐length recombinant PGRN (PGRN‐FL) and a PGRN‐derived fragment (FBAC). Inflammatory status was evaluated by bronchoalveolar lavage fluid and histopathologic analyses. Human bronchial epithelial cells were stimulated with DEPs and house dust mites (HDMs), and the effect of FBAC treatment was evaluated by assessing various intracellular signaling molecules, autophagy markers, inflammatory cytokines, and intracellular oxidative stress.DEP exposure exaggerated neutrophilic inflammation, enhanced IL‐6 and CXCL15 secretions, and increased oxidative stress in the murine model; this effect was greater in PGRN‐deficient mice than in wild‐type mice. The DEP‐exposed mice with PGRN‐FL treatment revealed no change in neutrophil infiltration and higher oxidative stress status in the lungs. On the contrary, FBAC administration inhibited neutrophilic infiltration and reduced oxidative stress. In human bronchial epithelial cells, DEP and HDM exposure increased intracellular oxidative stress and IL‐6 and IL‐8 secretion. Decreased nuclear factor erythroid 2‐related factor 2 (Nrf2) expression and increased phosphor‐p62 and LC3B expression were also observed. FBAC treatment attenuated oxidative stress from DEP and HDM exposure.FBAC reduced neutrophilic inflammation exaggerated by DEP exposure in a mouse model of allergic airway inflammation by reducing oxidative stress. PGRN and PGRN‐derived proteins may be novel therapeutic agents in attenuating asthma exacerbation induced by air pollutant exposure. [ABSTRACT FROM AUTHOR]

Postoperative cognitive dysfunction (POCD) poses a significant threat to patients undergoing anesthesia and surgery, particularly elderly patients. It is characterized by diminished cognitive functions post surgery, such as impaired memory and decreased concentration. The potential risk factors for POCD include age, surgical trauma, anesthetic type, and overall health condition; however, the precise mechanisms underlying POCD remain elusive. Recent studies suggest that neuroinflammation might be a primary pathogenic factor. NOD-, LRR- and pyrin domain-containing protein 3 (NLRP3) inflammasomes are implicated in exacerbating POCD by promoting the release of inflammatory factors and proteins that initiate pyroptosis, further influencing the disease process. The regulation of NLRP3 inflammasome activity, including its activation and degradation, is tightly controlled through multiple pathways and mechanisms. In addition, autophagy, a protective mechanism, regulates the NLRP3 inflammasome to control the progression of POCD. This review reviews recent findings on the role of the NLRP3 inflammasome in POCD pathogenesis and discusses therapeutic strategies aimed at reducing NLRP3 sources, inhibiting cellular pyroptosis, and enhancing autophagy. [ABSTRACT FROM AUTHOR]

Background: Protective measures applied during the Covid-19 pandemic had a marked impact on the incidence of pneumonia. However, systematic data are lacking for hospitalizations for pneumonia and acute exacerbations of chronic obstructive lung diseases (AECOPD) not caused by SARS-CoV-2 in Switzerland. We aimed to compare the incidences of hospitalization for these entities between 2020/2021 and prepandemic years. Methods: This retrospective study examined all nationwide hospitalizations for non-Covid-19-pneumonia and AECOPD listed as primary diagnoses based on ICD-10 codes between 2015 and 2021 in a publicly available hospitalization database of the Swiss Federal Statistical Office. Hospitalizations for acute coronary syndrome (ACS) and stroke were used as controls. Changes of monthly incidences of hospitalizations, length of stay (LOS) and mortality were compared between 2020/2021 and the average of 2015–2019. Results: The incidences of hospitalizations for AECOPD and for pneumonia showed seasonal variations from 2015 to 2019 followed by significant and almost identical decreases in 2020/2021 (incidence rate ratio [IRR] 0.59, 95% CI: 0.45–0.77, p < 0.001, and IRR: 0.62, 95% CI: 0.52–0.74, p < 0.001, respectively). Hospital-mortality was slightly higher in 2020/2021 for AECOPD (2015–2019: 3.8%; 2020/2021: 4.2%, odds ratio [OR] 1.24, 95% CI: 1.07–1.44, p = 0.004) and for pneumonia (2015–2019: 4.5%, 2020/2021: 4.6%, odds ratio [OR] 1.17, 95% CI: 1.07–1.28, p < 0.001). Median LOS slightly decreased for AECOPD (2015–2019: 8 [IQR: 5–14] days; 2020/2021: 7 [IQR: 4–13] days, Wilcoxon test: p < 0.001) but slightly increased for pneumonia (2015–2019: 7 [IQR: 4–11] days; 2020/2021: 7 [IQR: 4–13] days, Wilcoxon test: p < 0.001). Throughout 2020/2021, there were no significant fluctuations observed in the incidences of ACS and stroke. (IRR: 0.98, 95% CI: 0.83–1.16, p = 0.810, IRR: 0.96, 95% CI: 0.81–1.14, p = 0.636, respectively). Conclusion: The first two years of the Covid-19 pandemic showed a marked decrease in incidences in AECOPD and non-Covid-19 pneumonia hospitalizations in Switzerland. It is likely that this effect is associated with the society-based, at first vigorous, social distancing measures. [ABSTRACT FROM AUTHOR]

Background/Objectives: Frailty is a common condition among older adults and is associated with an increased risk of adverse health outcomes, including mortality, disability, dysmobility, falls, and hospitalization. In patients with atrial fibrillation (AF), these risks are further exacerbated. However, evidence linking AF and frailty, particularly in the South American context, is limited. This study aimed to assess frailty and other geriatric conditions in older outpatients with atrial fibrillation in a resource-limited setting in Lima, Peru. Methods: In this cross-sectional study, we included adults aged 60 years and older diagnosed with atrial fibrillation who were attending outpatient check-ups. Patients who were hospitalized, receiving chemotherapy induction, or presenting with acute infections or exacerbations were excluded. Standardized questionnaires were used to assess frailty, cognitive impairment, and functional dependence. Statistical analysis was performed using R Studio version 4.3.1, with a significance level set at p < 0.05. Results: Among the 200 patients who agreed to participate (mean age 74.76 ± 8.42 years, 41% females), 28.5% exhibited frailty, and 46.5% were classified as prefrail. Frailty and prefrailty were significantly associated with older age (p<0.01), female gender (p = 0.01), illiteracy (p<0.01), heart failure (p<0.01), falls (p<0.05), cognitive impairment (p<0.01), and functional dependence (p<0.01). Multivariate analysis revealed significant associations between frailty and cognitive impairment (p<0.05), frailty and functional dependence (p<0.05), and cognitive impairment and functional dependence (p<0.05). Conclusions: One-third of older outpatients with atrial fibrillation were identified as frail, while half were classified as prefrail. In this population, frailty frequently coexists with cognitive impairment and functional dependence, highlighting the need for timely screening and the implementation of evidence-based interventions for individuals with atrial fibrillation in resource-limited settings. [ABSTRACT FROM AUTHOR]

Background: Acute exacerbations of COPD (AECOPD) are common and significantly contribute to mortality in patients with COPD. Prognostic scores can assist clinicians in making tailored decisions to manage AECOPD. In the current study, we therefore aimed to evaluate the performance of the Noninvasive Ventilation Outcomes (NIVO) score, originally designed to assess in-ICU mortality, in predicting 1 year mortality and NIV failure in AECOPD. Methods: This retrospective study analyzed data from patients hospitalized for AECOPD requiring mechanical ventilation between January 1st, 2018, and December 31st, 2022. Mortality was assessed at the end of ICU stay and 1 year after admission, while NIV failure was defined as intubation or death without intubation. Results: Among 302 ICU admissions of COPD patients, 190 patients with AECOPD requiring mechanical ventilation were included. Of these, 44 (23%) died in the ICU, 62 out of 184 (34%) failed NIV, and 78 (41%) died within 1 year of admission. Patients who died in ICU or experienced NIV failure had more severe COPD and more impaired blood gas parameters at admission. The NIVO score demonstrated an AUC of 0.68 in predicting 1-year mortality and an AUC of 0.85 in predicting NIV failure. A NIVO score over 7 was associated with higher 1-year mortality and NIV failure (HR of 4.4 [1.8–10.9] and 41.6 [5.6–307.9], respectively). Conclusion: Beyond predicting in-ICU mortality, the NIVO-score is a reliable tool in predicting 1-year mortality and NIV failure in AECOPD. [ABSTRACT FROM AUTHOR]

Background: We evaluated the diagnostic value of homocysteine (Hcy) levels combined with the Wells score and established a prediction model for venous thromboembolism (VTE) occurrence in patients with acute exacerbations of chronic obstructive pulmonary disease (AECOPD) based on the Hcy level and the Wells score. Patients and methods: Clinical information from 914 patients with AECOPD was retrospectively collected in our hospital from June 2020 to October 2023. Receiver operating characteristic curves were plotted to evaluate the diagnostic ability of Hcy concentrations combined with Wells scores and the prediction ability of the model. Univariate and multivariate logistic regressions were used to explore the effects of Hcy levels and the Wells score on VTE occurrence. A nomogram was established for individual risk evaluation. Results: Hcy levels and Wells scores were significantly greater in the VTE group than in the non-VTE group (P < 0.001). The diagnostic ability of Hcy levels combined with the Wells score was greater than that Hcy levels or the Wells score alone. The AUC of the combined parameters was 0.935, with a sensitivity of 0.864 and a specificity of 0.855. Multivariate logistic regression indicated that elevated Hcy levels (OR:5.17, 95%CI: 3.76–7.09, P < 0.001) and Wells score (OR: 5.26, 95%CI: 3.22–8.59, P < 0.001) were independently associated with the risk of developing VTE in AECOPD patients. Decision curve analysis indicated that the net benefit of the nonadherence prediction nomogram was greater than that of the models adjusted for no or all variables, with a threshold of approximately 0.1-1.0. Conclusions: The established prediction model can be used to evaluate an individual's risk of developing VTE on the basis of the Hcy level, Wells score, and clinical parameters. AECOPD patients may benefit from the early intervention based on estimated risk probability. [ABSTRACT FROM AUTHOR]

Background: Evidence on how decisions regarding escalation to triple therapy and de- or re-escalation are taken and the rationale on which these decisions are based is currently limited in Germany. Objectives: The TETRIS study aims to elucidate influences on treatment decisions surrounding triple therapy in a real-world practice setting in Germany. Design: TETRIS is an ongoing, multicenter, prospective, observational cohort study recruiting patients with chronic obstructive pulmonary disease (COPD) with or without asthma who have already been treated with triple therapy for 2–48 weeks. Methods: For better representation of the treatment reality in Germany, patients are recruited from general practitioners and pulmonologists. Data are collected in two parts. Part 1 involves cross-sectional phenotyping of patients at enrollment. Part 2 involves a 2-year longitudinal follow-up period to monitor/document all visits by the patients during the 24-month observation period per routine clinical practice. Here, we report the demographic and baseline characteristics of 1213 eligible patients recruited to part 1 of the study. Results: The mean patient age was 66.4 years overall, and 29.3% (356/1213) of patients had no comorbidities. The mean CAT score was 19.4; the number of exacerbations and hospitalizations due to exacerbations in the past 3 years before starting triple therapy was 0.6 and 0.1, respectively. Dual bronchodilation with a long-acting muscarinic antagonist (LAMA) plus a long-acting β-2 agonist (LABA) was the most common therapy for COPD before initiation of triple therapy in 58.3% of patients. Conclusion: In this real-world setting in Germany, patients with COPD have a relatively low reported exacerbation rate but high symptom burden, and over 70% are multimorbid. Triple therapy is initiated in patients who are primarily highly symptomatic despite being on LAMA + LABA. Future prospective studies in patients with multimorbidity are warranted to better understand the treatment landscape across the disease spectrum. Trial registration: https://clinicaltrials.gov/study/NCT04657211 [ABSTRACT FROM AUTHOR]

Background: Chronic obstructive pulmonary disease (COPD) represents an important health challenge, despite being preventable and manageable thanks to up-to-date recommendations. In Italy, the pharmaceutical care of COPD patients is still ill-timed and inaccurate. This study aimed to describe the treatment of COPD patients in Italy and possible switches following an exacerbation. Methods: This observational retrospective analysis of Italian administrative healthcare data from the Fondazione Ricerca e Salute (ReS) database identified patients aged ≥ 45 years with COPD in 2019 and 2020. At least 6 years of look-back period and absence of concomitant asthma were required. COPD patients were categorized by treatment (SI–single/MI–multiple inhalers, TT–triple therapy, DT–dual therapy, other respiratory treatments, untreated) at index date (first dispensation during accrual period). Occurrence of moderate/severe exacerbation during one-year preceding index date and treatments during one-year preceding the exacerbation (possible switch) were evaluated. Results: From ~ 4.7 million beneficiaries of the Italian National Health Service in 2019 and 2020, respectively, 105,828 and 103,729 (43 and 41 × 1,000 inhabitants aged ≥ 45 years) were identified as having COPD. Of 2019/2020 patients: 3.4%/5.2% received SI-TT, 20.7%/17.5% MI-TT, 35.9%/38.1% DT, 33.0%/33.1% other treatments, and 7.0%/6.0% were untreated. Males were prevalent and median age was > 73 years for all groups. Of 2019/2020 cohorts, heart failure and coronary artery disease affected 24/20%, 18/17%, and 11%/16% patients with SI-TT, MI-TT, DT, and other treatments, respectively. A previous moderate/severe exacerbation (2019/2020 patients) occurred to 60.5%/56.6%, 39.9%/37.4%, 30.8%/29.2% and 31.9%/29.7% patients treated with SI-TT, MI-TT, DT, and other treatments, respectively. Of 2019/2020 patients experiencing moderate/severe exacerbation: 6.0%/7.0% receiving DT, 5.1%/7.0% receiving other treatments and 4.5%/10.0% untreated, switched to SI-TT; 23.7%/16.9% receiving DT, 21.4%/17.7% receiving other treatments and 15.4%/12.0% untreated, switched to MI-TT. Conclusions: COPD patients receiving TT were older and had more comorbidities, especially cardiovascular diseases, than patients receiving DT or other treatments. The limited number of patients switching after exacerbation suggests that many COPD patients may be inappropriately treated. Ensuring early and adequate treatment, combination of in-hospital and outpatient management, and integration of specialist and primary care is pivotal for the appropriate clinical management of COPD patients. [ABSTRACT FROM AUTHOR]

Background: Dual bronchodilator therapy, consisting of a long-acting beta-agonist (LABA) and a long-acting muscarinic antagonist (LAMA), has proven effective for patients with chronic obstructive pulmonary disease (COPD). However, it remains uncertain whether there are efficacy differences between current and former smokers with COPD. This study aims to explore the effectiveness of LABA/LAMA therapies in both these groups. Methods: The TOReTO trial assessed lung function, symptoms, health status, the occurrence of exacerbations, clinically significant exacerbations, and the use of LABA/LAMA therapies. These therapies include Tio/Olo, umeclidinium/vilanterol (Umec/Vi), and umeclidinium/vilanterol (Umec/Vi) are used in patients with COPD. The study examined the differences in outcomes between current and former smokers. To balance the baseline characteristics, propensity score matching (PSM) was employed. Results: Data from 967 patients were collected. After PSM, the time to the first acute exacerbation in current smokers was analyzed separately for the three treatment groups and was significantly different between them (p = 0.0457). Among, there are differences in the occurrence of acute exacerbation between treatment and smoking status in Umec/Vi (p = 0.0114). There is no significant difference in the treatment of former smokers among the three different groups of LABA/LAMA fixed-dose combinations (p = 0.3079). COPD-related symptoms remained stable throughout the treatment period. There were no significant differences in symptom scores, including CAT and mMRC, among the three groups at the end of the study. Conclusions: The three fixed-dose combinations of LABA/LAMA showed no difference in reducing exacerbations in former smokers but did show differences in current smokers. This trend has clinical significance, and future research will be conducted to control influencing variables to validate this point. However, due to the non-randomized study design, these findings should be interpreted with caution. [ABSTRACT FROM AUTHOR]

Introduction: Patients hospitalized due to dyspnea sometimes also report concomitant chest pain. Whether co-existing chest pain in patients with acute dyspnea associates with specific diagnosis and clinical outcome is not known. Method: We included 313 patients admitted to Akershus University Hospital with acute dyspnea and asked the patients directly on hospital admission whether they had experienced chest pain during the last 24 h. We examined the associations between chest pain and (1) diagnosis of the index hospitalization and (2) clinical outcome during follow-up. The diagnosis for the index hospitalization was adjudicated as acute heart failure (HF) or non-HF etiology of acute dyspnea by two experts working independently. Non-HF patients were further sub-grouped into chronic obstructive pulmonary disease (COPD) or non-COPD etiology. Results: In total, 143 patients were admitted with acute HF (46% of the population), 83 patients with COPD (26% of the population), and 87 patients with non-HF, non-COPD-related dyspnea (28% of the population). Ninety-six patients (31%) with acute dyspnea reported chest pain during the last 24 h prior to hospital admission. The prevalence of chest pain was not statistically different for patients who were hospitalized with acute HF (n = 42, 44%), acute exacerbation of COPD (n = 22, 23%), or non-HF, non-COPD-related dyspnea (n = 32, 33%), p > 0.05 for all comparisons between groups. During median of 823 days follow-up, 114 patients died (36%). Patients with dyspnea and concomitant chest pain did not have different outcome compared to patients with dyspnea and no chest pain (log-rank test: p = 0.09). Chest pain prior to admission was neither associated with all-cause mortality in any of the adjudicated diagnosis groups. Conclusions: Chest pain was reported in 31% of patients hospitalized with acute dyspnea but the prevalence did not differ according to adjudicated diagnosis. Patients with dyspnea and chest pain did not have worse outcome compared to patients with dyspnea and no chest pain. [ABSTRACT FROM AUTHOR]

Background/Objectives: The interpretation of evidence on the de-escalation of triple therapy with the withdrawal of inhaled corticosteroids (ICSs) to dual bronchodilator therapy with a long-acting muscarinic antagonist (LAMA) and a long-acting beta-agonist (LABA) in patients with chronic obstructive pulmonary disease (COPD) is conflicting. We evaluated the efficacy and safety of ICS discontinuation from LABA-LAMA-ICS triple therapy compared to its continuation. Methods: We searched PubMed, Embase, Scopus, Web Of Science, clinicaltrial.gov, and CENTRAL for RCTs and observational studies from inception to 22 March 2024, investigating the effect of triple therapy de-escalation with the withdrawal of ICSs to dual therapy on the risk of COPD exacerbation, pneumonia, and lung function. This study was registered with PROSPERO, CRD42024527942. Results: A total of 3335 studies was screened; 3 RCTs and 3 real-world non-interventional studies were identified as eligible. The analysis of the time to the first moderate or severe exacerbation showed a pooled HR of 0.96 (95% CI, 0.80–1.15; I2 = 77%) for ICS withdrawal compared to triple therapy continuation. The analysis according eosinophil levels showed that COPD subjects with ≥300 eosinophils/µL had a significant increase in the incidence of moderate or severe exacerbations when de-escalated to LABA/LAMA (pooled HR: 1.35, 95% CI: 1.00–1.82; I2: 56%). ICS withdrawal did not significantly affect the risk of mortality and pneumonia. Conclusions: The de-escalation of triple therapy with ICS withdrawal does not affect the main outcomes evaluated (moderate or severe exacerbations, change in trough FEV1). COPD patients with high blood eosinophils (≥2% or ≥300 cells/µL) are most likely to benefit from continuing triple therapy. [ABSTRACT FROM AUTHOR]

Background/Objectives: High-flow nasal therapy (HFNT) has been shown to reduce exacerbations of COPD and some evidence displays benefits in non-cystic fibrosis bronchiectasis (NCFB) patients. The present study aimed to compare the effectiveness of 12 months of home HFNT on the annual exacerbation rate between mild/moderate and severe NCFB patients, classified by the bronchiectasis severity index (BSI). Secondary outcomes were the evaluation of the dyspnea, pulmonary function, and sputum cultures in both groups. Methods: The study population included NCFB adult patients, with at least one severe exacerbation in the previous year on optimized therapy. NCFB exacerbations, dyspnea (mMRC score), pulmonary function test, and sputum cultures were assessed at baseline and after 12 months of HFNT. Results: A total of 86 NCFB patients were enrolled: 36 in the mild/moderate (BSI < 9) and 50 in the severe (BSI ≥ 9) group. A significant improvement in the annual exacerbation rate was found in both BSI ≥ 9 (p < 0.0001) and BSI < 9 cohorts (p < 0.0001), with a between-group difference of −1 (95% CI: −2 to 0) exacerbations per year (p = 0.0209). The change in the annual exacerbation rate was significantly correlated with BSI (ρ = −0.26, p = 0.0151) and with HFNT daily use (ρ = −0.22, p = 0.0460). The mMRC score significantly improved by −2 points (95% CI: −2 to −1) after treatment in both groups (p < 0.0001). The percentage of patients with P. aeruginosa colonization decreased from 34.9% to 27.9%. Conclusions: Long-term HFNT reduces the annual exacerbation rate in NCFB patients and its effectiveness increases alongside disease severity and daily use of HFNT. [ABSTRACT FROM AUTHOR]

Rationale: Respiratory syncytial virus (RSV) is a common global respiratory virus that is increasingly recognized as a major pathogen in frail older adults and as a cause of chronic obstructive pulmonary disease (COPD) exacerbations. There is no single test for RSV in adults that has acceptable diagnostic accuracy. Trials of RSV vaccines have recently shown excellent safety and efficacy against RSV in older adults; defining the frequency of RSV-related community infections and COPD exacerbations is important for vaccine deployment decisions. Objectives: This prospective study aimed to establish the frequency of outpatient-managed RSV-related exacerbations of COPD in two well-characterized patient cohorts using a combination of diagnostic methods. Methods: Participants were recruited at specialist clinics in London, United Kingdom, and Groningen, the Netherlands, beginning in 2017 and observed for three consecutive RSV seasons, during exacerbations, and at least twice yearly. RSV infections were detected by RT-PCR and serologic testing. Measurements and Main Results: A total of 377 patients with COPD attended 1,999 clinic visits and reported 310 exacerbations. There were 27 RSV-related exacerbations (8.7% of the total); of these, seven were detected only by PCR, 16 only by serology, and four by both methods. Increases in RSV-specific Nucleoprotein antibody were as sensitive as those in the antibody to Pre-Fusion or Post-Fusion for serodiagnosis of RSV-related exacerbations. Conclusions: RSV is associated with 8.7% of outpatient-managed COPD exacerbations in this study. Antibodies to RSV Nucleoprotein may have diagnostic value and are potentially important in a vaccinated population. The introduction of vaccines that prevent RSV is expected to benefit patients with COPD. [ABSTRACT FROM AUTHOR]

Background: Patients with idiopathic interstitial pneumonia (IIP) often exhibit positivity for myositis-specific antibodies (MSA). However, the significance of this finding remains unclear. In this study, we investigated the association of MSA with the prognosis and risk of acute exacerbation in patients with IIP. Methods: We retrospectively reviewed the medical records of patients with IIP and examined the effect of each MSA subtype on survival and acute exacerbation. Results: Of 240 patients with IIP, 48 (20%) exhibited positivity for MSA. The MSA subtypes included: PL-7 (antithreonyl; n = 16, 6.7%); signal recognition particle (n = 13, 5.4%); PL-12 (antialanyl; n = 9, 3.8%); Mi-2 (n = 8, 3.3%); OJ (anti-isoleucyl; n = 7, 2.9%). During the 382 days (382 ± 281 days) of observation, 32 (13%) patients expired, and 27 (11%) experienced an acute exacerbation. Cox proportional hazards regression analysis demonstrated that age at the initial visit (hazard ratio [HR]: 1.072; 95% confidence interval [CI]: 1.017–1.131; P = 0.01), PL-7 (HR: 4.785; 95% CI: 1.528–14.925; P = 0.007), and PL-12 (HR: 3.922; 95% CI: 1.198–12.82; P = 0.024) were independent predictors of survival time. PL-7 (HR: 3.268; 95% CI: 1.064–10; P = 0.039) and PL-12 (HR: 5.747; 95% CI: 1.894–7.544; P = 0.002) were independent predictors of time from first visit to acute exacerbation. Conclusion: Detecting MSA in patients with interstitial lung disease may be useful in predicting prognosis and providing a rationale for intensive treatment. [ABSTRACT FROM AUTHOR]

Background: To assess the effect of pneumonia on the risk of mortality and other clinical outcomes in patients with acute exacerbation of chronic obstructive pulmonary disease (AECOPD). Methods: PubMed, EMBASE and Scopus were screened for observational cohort and case-control studies that reported outcomes in AECOPD patients with and without pneumonia. Pooled effect sizes were reported as relative risks (RR) or hazard ratio (HR) for categorical outcomes and as weighted mean difference (WMD) for continuous outcomes. The primary outcome was mortality. Secondary outcomes were risk of admission to intensive care unit (ICU), need for assisted ventilation and readmission as well as duration of stay at the hospital. The certainty of the evidence was assessed using the GRADE approach. Results: Thirteen studies were included. AECOPD patients with pneumonia had significantly higher risk of in-hospital mortality (RR 2.29, 95% CI: 1.40, 3.73), mortality at 1 month (RR 1.84, 95% CI: 1.09, 3.13), and 1 year or more of follow-up (HR 2.30, 95% CI: 1.15, 4.61) compared to AECOPD patients without pneumonia. Pneumonia was associated with significantly higher risk of admission to ICU (RR 2.79, 95% CI: 1.47, 5.28), need for assisted ventilation (RR 2.02, 95% CI: 1.52, 2.67), and longer hospital stay (in days) (WMD 3.31, 95% CI: 2.33, 4.29). The risk of readmission was comparable in the two groups of patients (RR 1.07, 95% CI: 0.97, 1.19). The overall quality of evidence for the outcomes was judged to be "Low". Conclusion: Pneumonia during acute exacerbation of COPD may lead to increases in both short-term and long-term mortality as well as increased hospital stay, need for ventilatory support and admission to ICU. Our findings suggest the need for close monitoring, early intervention, and long-term follow-up, to improve the outcomes in AECOPD patients with concurrent pneumonia. [ABSTRACT FROM AUTHOR]

The prevalence of many chronic noncommunicable diseases has been steadily rising over the past six decades. During this time, over 350,000 new chemical substances have been introduced to the lives of humans. In recent years, the epithelial barrier theory came to light explaining the growing prevalence and exacerbations of these diseases worldwide. It attributes their onset to a functionally impaired epithelial barrier triggered by the toxicity of the exposed substances, associated with microbial dysbiosis, immune system activation, and inflammation. Diseases encompassed by the epithelial barrier theory share common features such as an increased prevalence after the 1960s or 2000s that cannot (solely) be accounted for by the emergence of improved diagnostic methods. Other common traits include epithelial barrier defects, microbial dysbiosis with loss of commensals and colonization of opportunistic pathogens, and circulating inflammatory cells and cytokines. In addition, practically unrelated diseases that fulfill these criteria have started to emerge as multimorbidities during the last decades. Here, we provide a comprehensive overview of diseases encompassed by the epithelial barrier theory and discuss evidence and similarities for their epidemiology, genetic susceptibility, epithelial barrier dysfunction, microbial dysbiosis, and tissue inflammation. [ABSTRACT FROM AUTHOR]

Background: Exacerbation of chronic obstructive pulmonary disease (ECOPD) results in severe adverse outcomes and mortality. It is often associated with increased local and systemic inflammation. However, individual susceptibility to exacerbations remains largely unknown. Our study aimed to investigate the association between comorbidities and exacerbation outcomes. Methods: We included patients with the primary discharge diagnosis of exacerbation for more 10 years in China. Data on all comorbidities were collected and analysed to determine the impact of the comorbidities on 1-year exacerbation readmission, length of hospital stay, and hospital cost. Univariable and multivariable logistic regression analyses were performed, and predictive models were developed. Results: This extensive investigation evaluated a total of 15,708 individuals from five prominent locations in China, revealing notable variations in the prevalence of comorbidities and healthcare expenses among different regions. The study shows that there is a high rate of readmission within one year, namely 15.8%. The most common conditions among readmitted patients are hypertension (38.6%), ischemic heart disease (16.9%), and diabetes mellitus (16.6%). An extensive multivariable study revealed that age, gender, and particular comorbidities such as malnutrition and hyperlipidemia are important factors that can significantly predict greater readmission rates, longer hospital stays or increased healthcare costs. The multivariable models show a moderate to good ability to predict patient outcomes, with concordance index ranging from 0.701 to 0.752. This suggests that targeted interventions in these areas could improve patient outcomes and make better use of healthcare resources. Conclusions: The results regarding the association between severe exacerbations and systemic disease status support the integration of systematic evaluation of comorbidities into the management of exacerbations and the intensification of treatment of important comorbidities as a appropriate measure for prevention of further exacerbations. Our models also provide a novel tool for clinicians to determine the risk of the 1-year recurrence of severe ECOPD in hospitalised patients. [ABSTRACT FROM AUTHOR]

Introduction: Buprenorphine is used to treat opioid use disorder (OUD). However, therapy is often disrupted during acute pain episodes, and re-initiation is often deferred due to intolerable interruption in opioid analgesics. This case report describes a unique strategy for inducing buprenorphine without stopping opioid analgesics. Case: One patient with OUD and acute pain was initiated on buprenorphine using intravenous microdosing without precipitated withdrawal or pain exacerbation. Full agonist opioids were successfully weaned after discharge and the patient was linked with a community-based treatment program. Conclusion: This case describes use of intravenous buprenorphine to treat OUD and acute pain without adverse consequences. [ABSTRACT FROM AUTHOR]

Objective: The aim of this study is to ascertain whether COVID‐19 Omicron infection is associated with exacerbations in these myasthenia gravis (MG) patients. Result: In total, 289 MG patients (comprising 60% females, with an average age of 46 ± 15 years) were enrolled. A total of 80.9% of MG patients reported a COVID‐19 infection, with the majority experiencing a benign course (88%). MG patients who experienced COVID‐19 infection demonstrated a higher likelihood of MG exacerbation, compared to those without the infection (18.8% vs. 7.3%, p = 0.039). In the survival analysis, after adjusting for confounding factors, the hazard ratio (HR) for exacerbation post‐infection was found to be 3.38 (95% CI 1.20–9.53, p = 0.021). Compared to the exacerbation rates observed in JTA21, an increase was noted in DTM23 among COVID‐19‐infected MG patients (4.4% vs. 17.2%, p < 0.001). Conclusion: The COVID‐19 is the risk of MG exacerbation. [ABSTRACT FROM AUTHOR]

Human rhinovirus (HRV) infections are the leading cause of disease exacerbations in individuals with chronic pulmonary diseases, primarily due to impaired macrophage functions, resulting in defective bacterial elimination. We previously demonstrated that HRV16 impairs macrophages' functions in an ARL5b-dependent manner. In permissive cells, ARL5b acted as an HRV16 restriction factor and was repressed. Here, we delve into the dual regulation of ARL5b by HRV16 in both cell types. We analyzed the effect of HRV16 on primary human macrophages using neutralizing antibodies, specific inhibitors, siRNA, and chromatin immune precipitation. Our study reveals that, while the virus does not replicate in macrophages, it induces interferon and pro-inflammatory responses. We identify the ICAM-1-PKR-ATF2 signaling axis as crucial for ARL5b induction in macrophages, whereas only ICAM-1 plays a role in ARL5b repression in permissive cells. Furthermore, HRV16 triggers epigenetic reprogramming in both cell types at the ARL5b promoter. In macrophages, epigenetic changes are ATF2 dependent. In conclusion, our findings highlight previously unknown signaling pathways activated by HRV16 in macrophages. Targeting these pathways could offer novel strategies to improve outcomes for individuals with respiratory conditions. [ABSTRACT FROM AUTHOR]

Background- Both individuals with acute exacerbation of COPD and those with stable COPD showed a number of abnormalities on their ECG. Local data on acute exacerbations are, however, scarce. Therefore, in order to enhance the interpretation of ECG results, identify the related cardiac abnormality and appropriate therapy, and lower the risk of morbidity, this study aimed to identify ECG changes in COPD patients and to correlate it with the disease severity. Methods and materials- This was a prospective observational study performed in the Department of Pulmonology in a tertiary care hospital from January 2022 to December 2023 on all patients diagnosed with COPD. ECG was taken for all patients, and changes were assessed. Results- The most common ECG finding was P-pulmonale in E group, followed by Poor R wave progression and RVH/RAD. When we analysed the influence of COPD severity with ECG findings, we found a statistically significant correlation. Conclusion- ECG changes in COPD can help in early diagnoses of changes leading to cor pulmonale, and help rule out other cardiac anomalies. [ABSTRACT FROM AUTHOR]

Introduction: Chronic Obstructive Pulmonary Disease (COPD) is a leading cause of morbidity and mortality worldwide. Acute exacerbations of COPD (AECOPD) significantly impact patient outcomes and healthcare costs. Recent studies have shown interest in cardiac troponin I (cTnI) as a potential prognostic marker in AECOPD. This study aimed to evaluate the prognostic value of cTnI during AECOPD. Methods: This prospective observational study included 90 patients admitted with AECOPD over 18 months. Patients were divided into two groups based on admission cTnI levels: elevated (>0.01 ng/ml) and normal (<0.01 ng/ml). Demographic data, medical history, physical examination findings, and diagnostic test results were recorded. Outcomes including ICU admission, need for ventilation, length of stay, and mortality were assessed. Methods: This prospective observational study included 90 patients admitted with AECOPD over 18 months. Patients were divided into two groups based on admission cTnI levels: elevated (>0.01 ng/ml) and normal (<0.01 ng/ml). Demographic data, medical history, physical examination findings, and diagnostic test results were recorded. Outcomes including ICU admission, need for ventilation, length of stay, and mortality were assessed. Conclusion: Elevated cTnI during AECOPD is associated with higher disease severity and increased need for intensive care. While it does not predict length of stay or in-hospital mortality, cTnI can serve as a valuable marker for identifying high-risk patients at admission. Further studies are needed to evaluate long-term outcomes in patients with elevated cTnI during AECOPD. [ABSTRACT FROM AUTHOR]

Background: Magnesium plays an important role in bronchodilation and has anti-inflammatory effects. Hypomagnesaemia has been associated with increased risk of acute exacerbations in chronic obstructive pulmonary disease (COPD). This study aimed to evaluate the relationship between serum magnesium levels and clinical outcomes in patients hospitalized for acute exacerbation of COPD (AECOPD). Methods: This prospective observational study enrolled 45 patients admitted with AECOPD. Serum magnesium levels were measured at admission. Patients were followed until discharge, and duration of hospital and intensive care unit (ICU) stay were recorded. The association between serum magnesium and length of stay was analyzed using correlation and regression analyses. Results: The mean age of study participants was 69.9±10.2 years. The mean duration of COPD was 9.13±4.7 years. The mean serum magnesium level was 2± 0.48 mg/dL. Lower serum magnesium levels correlated with longer hospital stay (r = -0.517, p < 0.001) and ICU stay (r = -0.570, p < 0.001). Conclusions: Hypomagnesaemia at admission is associated with longer hospital and ICU stays in patients hospitalized for AECOPD. Serum magnesium levels may serve as a prognostic biomarker, and magnesium supplementation warrants further study as a potential intervention to improve clinical outcomes during COPD exacerbations. [ABSTRACT FROM AUTHOR]

Aim:To study clinico-demographic and lung spirometry profile between non-smoker and smoker COPD patients. Material & Methods: The present cross-sectional observational study was conducted among 200 clinically diagnosed COPD patients attending the Pulmonary Medicine Department at tertiary care centre, Bhopal, Madhyapradesh. Upon diagnosis of COPD, detailed past medical history and any previous exposures was recorded. Patients aged <18 years and patients who do not provide consent were excluded from the patients. Informed consent was taken from all the patients and ethical clearance was obtained form institutional ethical committee. Result: Out of 200 COPD patients, 134(67%) were non smokers and 66(33%) were smokers. Out of 200 COPD patients, 150 were male & 50 were female. Smokers experienced a higher frequency of acute exacerbations (3-5 times) compared to non-smokers, suggesting that smoking exacerbates the severity and recurrence of COPD episodes.(P=0.001) Smokers had a significantly higher mean CAT score compared to non-smokers, indicating more severe COPD symptoms and a greater impact on daily life for smokers.(P=0.001) Smokers had more severe shortness of breath (higher mMRC grades) compared to nonsmokers, indicating a greater impact of smoking on the severity of COPD symptoms. Conclusion: Present study found that an Environmental and occupational exposures are significant contributors to COPD among non-smokers, with biofuel smoke and second-hand smoke being primary risk factors. [ABSTRACT FROM AUTHOR]

The landscape of clinical management for metastatic melanoma (MM) and other solid tumors has been modernized by the advent of immune checkpoint inhibitors (ICI), including programmed cell death-1 (PD-1), programmed cell death-ligand 1 (PD-L1), and cytotoxic T lymphocyte antigen 4 (CTLA-4) inhibitors. While these agents demonstrate efficacy in suppressing tumor growth, they also lead to immune-related adverse events (irAEs), resulting in the exacerbation of autoimmune diseases such as rheumatoid arthritis (RA), ulcerative colitis (UC), and Crohn's disease (CD). The immune checkpoint inhibitors offer promising advancements in the treatment of melanoma and other cancers, but they also present significant challenges related to irAEs and autoimmune diseases. Ongoing research is crucial to better understand these challenges and develop strategies for mitigating adverse effects while maximizing therapeutic benefits. In this manuscript, we addressed this challenge using network-based approaches by constructing and analyzing the molecular and signaling networks associated with tumor-immune crosstalk. Our analysis revealed that IL6 is the key regulator responsible for irAEs during ICI therapies. Furthermore, we conducted an integrative network and molecular-level analysis, including virtual screening, of drug libraries, such as the Collection of Open Natural Products (COCONUT) and the Zinc15 FDA-approved library, to identify potential IL6 inhibitors. Subsequently, the compound amprenavir was identified as the best molecule that may disrupt essential interactions between IL6 and IL6R, which are responsible for initiating the signaling cascades underlying irAEs in ICI therapies. [ABSTRACT FROM AUTHOR]

Desertification greatly threatens the ecological environment and sustainable development over approximately 30% of global land. In this study, the contributions of climate drivers and human activity in shaping the desertification process from 1984 to 2014 were quantified in the desertification-prone region (DPR) in Northern China (NC) by employing net primary productivity (NPP) as a proxy. The results reveal that 72.74% of the DPR experienced desertification mitigation and 27.26% experienced exacerbation. Climate drivers acted as primary drivers, contributing to both the mitigation (47.2%) and exacerbation (48.5%) of desertification, while human activity also played a crucial role, with contributions of 39.6% to mitigation and 41.0% to exacerbation of desertification. Furthermore, a shift in desertification dynamics emerged around 2000, with climate drivers promoting the mitigation process (66.8%), and precipitation was a dominant climatic factor for the mitigation of desertification after 2000, which was related to internal atmospheric variability. This study highlights changes in the contributions of different factors to desertification, underscoring the need for policy adjustment to attain sustainable land management in NC. [ABSTRACT FROM AUTHOR]

The evidence regarding the intergenerational effects of the Holocaust points to a heightened sensitivity to traumatic and stressful events, as well as to threats. These effects were found across at least three generations: the survivors themselves, their children, and their grandchildren. More specifically, this sensitivity is manifested in increased psychological reactions to adverse circumstances, especially when such situations trigger associations with the Holocaust. During 2023 Israel has experienced unprecedented civil unrest and protests following the government's plan to promote a judicial overhaul. Many expressed fears for Israeli democracy and the integrity of the social fabric in Israel. The current study examined how Holocaust descendants (i.e., children and grandchildren of Holocaust survivors) experienced this prolonged social unrest. A web‐based random sample of 706 Israeli Jews born after World War II completed questionnaires several months before the unrest began (Wave 1, 2022) and seven months into the unrest (Wave 2, 2023). Supporting most of our hypotheses, Holocaust descendants reported higher civil unrest salience (i.e., more preoccupation with the political and social upheaval) relative to comparison descendants (i.e., children and grandchildren of those not directly exposed to the Holocaust). Relative to comparison descendants, Holocaust descendants were also at a greater risk of reporting exacerbation in anxiety since the judicial overhaul was introduced, but not in depression or somatisation symptoms. Results remained significant after controlling Wave 1 distress level, background characteristics, level of engagement in civil unrest, and participants' viewpoint on the judicial overhaul. The findings further corroborate unique reactions to stress among Holocaust descendants, this time by highlighting increased preoccupation and increased exacerbation in anxiety during a period of prolonged political and social turmoil. [ABSTRACT FROM AUTHOR]

Introduction: Despite the importance of an adequate peak inspiratory flow (PIF) during inhaled therapy in patients with COPD, the available evidence in patients with severe exacerbations and their evolution after admission is limited. We conducted this study to evaluate the PIF during an exacerbation, its variability, and predictors of suboptimal PIF. Material and Methods: A prospective study that included patients admitted for COPD exacerbation. Clinical, demographic, and functional variables were recorded. Using the In-Check DIAL G16®, PIF without resistance (PIF-nr) and that obtained by simulating the resistance of the patients' usual inhalers (PIF) were determined within the first 48 hours of admission and prior to discharge; also assessed during a stable phase in a subgroup of patients. The results were compared and, through a multivariate study, the factors related to a suboptimal PIF were analyzed. Results: A total of 137 patients were included; 27% were women and the mean age was 69.4 ± 9.8 years. Moreover, 30.8% of the participants with dry powder inhalers had a suboptimal PIF at admission and it was independently associated with female sex (odds ratio [OR] = 8.635; 95% confidence interval [CI] [2.007, 37.152]; p < 0.01) and forced expiratory volume in the 1st second (FEV1) (OR = 0.997; 95% CI: [0.995, 0.999]; p = 0.04). At discharge, suboptimal PIF reduced to 17% (p < 0.01). PIF-nr increased from the time of admission to the stable phase. Conclusion: One third of COPD patients admitted with a severe exacerbation had a suboptimal PIF, being female sex and lower FEV1 independent predictors. PIF-nr improved progressively after the exacerbation. [ABSTRACT FROM AUTHOR]

Background: The association between blood eosinophils and COPD exacerbation has been controversial. This study aims to investigate whether high blood eosinophils predict the risk of COPD exacerbation across different thresholds and subgroups. Methods: PubMed, Embase and Web of science were searched for randomized controlled trial (RCT) and observational studies regarding the relationship between blood eosinophils and COPD exacerbation. Pooled risk ratio (RR) for COPD exacerbation was calculated using the Mantel-Haenszel method with a random-effects model. Results: A total of 21 studies (1 RCT and 20 observational studies) with 79868 participants were included. Thresholds of high blood eosinophils including absolute counts (200, 300 and 400 cell/μL) and percentages (2%, 3% and 4%) were analyzed respectively. Pooled analyses suggested that high blood eosinophils were significantly associated with increased risk of COPD exacerbation when using the thresholds of 300 cells/μL (RR 1.21, 95%CI 1.12–1.30, P <0.001, 16 studies), 400 cells/μL (RR 1.79, 95%CI 1.41–2.28, P <0.001, 3 studies), 2% (RR 1.26, 95%CI 1.02–1.55, P = 0.030, 10 studies) and 4% (RR 1.44, 95%CI 1.05–1.96, P = 0.022, 4 studies), but not 200 cells/μL and 3% (P>0.05). Moreover, high blood eosinophils contributed to moderate-severe exacerbation of COPD by the cutoffs of 300 cells/μL (RR 1.30, 95%CI 1.16–1.45, P<0.001, 11 studies) and 2% (RR 1.33, 95%CI 1.02–1.76, P = 0.037, 8 studies). In subgroup analyses, the pooled results further showed a significant association between high blood eosinophils (especially over 300 cells/μL) and risk of COPD exacerbation among patients from Europe and Asia, and whether with stable or exacerbation phase at baseline, and regardless of the follow-up time (≤ or > 1year). Conclusions: This study demonstrates that high blood eosinophils (over 300 cells/μL or 2%) could predict the risk of moderate-severe exacerbation of COPD in specific subgroups. However, large sample-sized, prospective, and well-designed studies are required to validate the present findings. [ABSTRACT FROM AUTHOR]

Background: Government programs—targeting chronic disease patients with high health care costs—focus on clinical conditions, factors internal to the health care system, and individual patient education, not on addressing modifiable social determinants of health to reduce health care utilization. Objective: To evaluate differences in sociodemographic variables and health care utilization between patients with chronic obstructive pulmonary disease (COPD) who reported food insecurity and those who did not. Methods: This descriptive retrospective cross-sectional study used data from the electronic health records of a convenience sample of 854 participants with a discharge diagnosis of COPD or COPD with acute exacerbation, admitted via the emergency department of participating hospitals in Southern California. Chi-square (or Fisher's exact) tests and t tests were used to evaluate group differences, and multivariate (or Firth) logistic regression to identify factors that increased the odds of emergency department visits and hospitalizations. Results: Significant differences between groups were identified for food insecurity (sometimes or often vs never insecure) and age (P <.001), race (P =.022), medical insurance (P <.001), zip code (P =.022), homeless status (P <.001), smoking status (P <.001), and emergency department visits (P =.033). No significant differences were found for food insecurity and hospitalizations (P =.592). Conclusion: This study contributes to the growing body of research supporting the association of upstream social factors (food insecurity, homelessness, zip code) and downstream health outcomes (repeated emergency room visits), and how existing programs can be effectively utilized to impact downstream health outcomes such as health care utilization. [ABSTRACT FROM AUTHOR]

Purpose: Bronchiectasis is predominantly marked by neutrophilic inflammation. The relevance of type 2 biomarkers in disease severity and exacerbation risk is poorly understood. This study explores the clinical significance of these biomarkers in bronchiectasis patients. Methods: In a cross-sectional cohort study, bronchiectasis patients, excluding those with asthma or allergic bronchopulmonary aspergillosis, underwent clinical and radiological evaluations. Bronchoalveolar lavage samples were analyzed for cytokines and microbiology. Blood eosinophil count (BEC), serum total immunoglobulin E (IgE), and fractional exhaled nitric oxide (FeNO) were measured during stable disease states. Positive type 2 biomarkers were defined by established thresholds for BEC, total IgE, and FeNO. Results: Among 130 patients, 15.3% demonstrated BEC ≥ 300 cells/μL, 26.1% showed elevated FeNO ≥ 25 ppb, and 36.9% had high serum total IgE ≥ 75 kU/L. Approximately 60% had at least one positive type 2 biomarker. The impact on clinical characteristics and disease severity was variable, highlighting BEC and FeNO as reflective of different facets of disease severity and exacerbation risk. The combination of low BEC with high FeNO appeared to indicate a lower risk of exacerbation. However, Pseudomonas aeruginosa colonization and a high neutrophil-to-lymphocyte ratio (NLR ≥ 3.0) were identified as more significant predictors of exacerbation frequency, independent of type 2 biomarker presence. Conclusions: Our study underscores the distinct roles of type 2 biomarkers, highlighting BEC and FeNO, in bronchiectasis for assessing disease severity and predicting exacerbation risk. It advocates for a multi-biomarker strategy, incorporating these with microbiological and clinical assessments, for comprehensive patient management. [ABSTRACT FROM AUTHOR]

Objectives: To examine the safety of cardiorespiratory fitness (CRF) assessment and training in the early sub-acute phase of recovery (≤3 months) following moderate-to-extremely severe traumatic brain injury (TBI). Methods: A systematic review was completed in accordance with the PRISMA guidelines. Studies investigating adults and adolescents ≥15 years with moderate-to-extremely severe TBI were considered for inclusion. The methodological quality of the included studies was evaluated according to the McMaster Guidelines for Critical Review Form – Quantitative Studies. Results: Eleven studies with a total of 380 participants were included in the review. Adverse events (AEs) and symptom monitoring were poorly reported. Only four studies reported on the occurrence of AEs, with a total of eight AEs reported. Three of the reported AEs were concussion-like symptoms with no further exercise-induced symptom exacerbation reported. No serious AEs were reported. Conclusion: There is no evidence to suggest that CRF assessment and training is unsafe in the early sub-acute phase of recovery following moderate-to-extremely severe TBI. However, despite the low AE and symptom exacerbation rates identified, a timeframe for safe commencement was unable to be established due to poor reporting and/or monitoring of exercise-induced symptoms and AEs in the current literature. [ABSTRACT FROM AUTHOR]

Tumour necrosis factor-α (TNF- α) antagonists are considered a significant therapeutic option in the treatment of sarcoidosis. Nevertheless, their use can also paradoxically result in sarcoidosis-like reactions. Here, we present a case of a 56-year-old patient with psoriatic arthritis who after 3 months of certolizumab therapy developed pulmonary sarcoidosis. Therefore, certolizumab was discontinued and prednisone initiated. Subsequently, 4 months later a complete remission of interstitial lesions was observed. Due to insufficient control of psoriatic arthritis, upadacitinib and methotrexate were prescribed and despite initial improvement, a couple of months later a massive exacerbation of skin psoriasis occurred and the treatment was switched to secukinumab. As of today, no evidence of sarcoidosis recurrence has been noted. Drug-induced sarcoidosis-like reactions (DISR) appear to be less frequently associated with certolizumab rather than with other anti-TNF-α agents. However, specific mechanisms of this phenomenon remain unclear and require future investigation. [ABSTRACT FROM AUTHOR]

Site-independent ratings derived from audio-digital recordings of site-based interviews are often used for quality assurance monitoring to affirm ratings reliability in CNS clinical trials. The present study of subjects with schizophrenia and persistent negative symptoms used video instead of audio recordings of site-based interviews and thereby facilitated visual observation of the subject by the remote rater. "Paired" site-independent scores of the Positive and Negative Syndrome Scale (PANSS) and Brief Negative Symptom Scale (BNSS) were obtained from video-recordings of site-based interviews. The intraclass correlation between site-based and paired site-independent ratings was r = 0.839 for the total PANSS scores (n = 1006) and r = 0.871 for the total BNSS scores (n = 892); <5 % of paired scores deviated outside the acceptable confidence intervals. Ratings "outliers" were identified and remediated. We examined the pattern of paired scoring deviations for the BNSS, total PANSS, PANSS symptom subscales, and the Marder negative symptom factor. Each metric revealed a bidirectional pattern of scoring deviations such that mean site-based ratings were higher than site-independent ratings when symptom severity was high but lower than site-independent ratings when symptom severity was low. The pattern of bidirectional paired scoring deviations observed in this analysis has previously been noted in paired ratings analyses of subjects experiencing an acute exacerbation of psychosis in schizophrenia and major depressive disorder as well. The bidirectional pattern may reflect inherent differences between live ratings and remotely scored recorded ratings. This analysis affirms the utility of video-recordings of site-based ratings for surveillance in trials with subjects with schizophrenia and persistent negative symptoms. [ABSTRACT FROM AUTHOR]

Schizophrenia is a complex psychiatric disorder with an unclear etiopathogenesis. This study investigates the plasma G72 protein levels in drug-naive schizophrenia patients (DNS), those in acute psychotic episodes (AES), and healthy controls (HC). It also examines the correlation between the plasma G72 protein levels and Positive and Negative Syndrome Scale (PANSS) scores. The study included 138 schizophrenia patients (84 DNS, 54 AES) and 83 HCs. Plasma G72 protein levels were measured by ELISA. Statistical analyses, including log-transformation and correlation analysis, were conducted. Schizophrenia patients had significantly lower plasma G72 levels than HCs (4.39 ± 5.38 vs. 8.06 ± 10.27 ng/mL, p < 0.001), while DNS and AES groups did not differ significantly. Log-transformed data confirmed these differences. Negative correlation was found between plasma G72 levels and age (r = −0.258, p = 0.02), PANSS-G (r = −0.249, p = 0.004), and total PANSS scores (r = −0.226, p = 0.008). ROC analysis showed poor discrimination between schizophrenia patients and controls (AUC: 0.587, p = 0.031). This study's novel findings reveal that plasma G72 protein levels are significantly lower in schizophrenia patients and inversely correlated with age and symptom severity. However, the poor diagnostic accuracy observed in the ROC analysis suggests that G72 may not be a reliable biomarker for schizophrenia at this stage. These results underscore the need for further research to explore the potential clinical implications of these findings. • Lower plasma G72 protein levels observed in schizophrenia patients. • Plasma G72 protein levels and age showed a negative correlation. • Negative correlation found between plasma G72 and symptom severity in schizophrenia. • ROC analysis suggests that plasma G72 may not be a reliable biomarker for schizophrenia. [ABSTRACT FROM AUTHOR]

Background: In 2019, according to WHO estimates, 262 million people were affected by asta, resulting in 455,000 deaths [1]. Asthma, is a chronic inflammatory disease of the airways that causes reversible bronchoconstriction, making it difficult for patients to breathe. Exacerbations of the disease can be caused by a variety of factors but share similar symptoms such as wheezing, coughing, shortness of breath and chest tightness. Severe asthma exacerbations are defined as symptoms that do not respond to inhaled medications and improve only after oral or intravenous steroid administration. Asthma-related deaths often occur during exacerbations. Vitamin D, which is produced naturally in the body and found in some foods, is a steroid-derived vitamin. Adequate doses of this vitamin, administered through medication or supplements, can be used to maintain its proper levels in the organism. Vitamin D is essential for regulating calcium levels in the body and for bone remodeling. It also has immunomodulatory effects, affecting both innate and adaptive immunity. This partly explains its association with changes in the airway epithelium that occur as a result of inflammation in asthma. [ABSTRACT FROM AUTHOR]

Background: Acute exacerbations of chronic obstructive pulmonary diseases (AECOPD) are a frequent cause of hospitalization, morbidity, and mortality and require serious medical attention. Much research has demonstrated the beneficial effects of intravenous and nebulized magnesium sulfate (MgSO4) as a bronchodilator, in the management of acute severe asthma. Nevertheless, the extent of the benefits of intravenous MgSO4 as an adjuvant to bronchodilators in AECOPD remains uncertain. Therefore, the current study aims to address this gap in knowledge. Aims and Objectives: The study aimed to compare the effectiveness of intravenous magnesium sulfate (MgSO4) versus placebo when used as an adjuvant to nebulized salbutamol in managing AECOPD. Materials and Methods: In this comparative prospective interventional, parallel-group, placebo-controlled study, a total of 60 subjects were assigned to two groups consisting of 30 individuals each. The allocation was non-randomized and open-label, with one group receiving intravenous MgSO4 as an adjuvant to nebulized salbutamol, while the other group received a placebo in the same manner. The evaluation of MgSO4 efficacy involved measuring the peak expiratory flow rate (PEFR), which served as the primary outcome parameter. PEFR measurements were taken at 0, 15, 30, and 45 min to assess the effectiveness of MgSO4. Safety and tolerability of MgSO4 were assessed based on changes in heart rate, blood pressure, deep tendon reflexes, and respiratory rate. Results: At 45 min, the mean change in PEFR was significantly higher (P = 0.061) in the MgSO4 group (178.33 ± 49.18) compared to the placebo group (155.43 ± 41.86). Moreover, the mean difference in PEFR between the two groups was consistently higher in the MgSO4 group at every observation. MgSO4 showed considerable safety and tolerability in subjects based on the postmedication monitoring of hypermagnesemia symptoms. Conclusion: Administering intravenous magnesium sulfate (MgSO4) as an adjuvant to bronchodilators in AECOPD led to the improvement of both clinical condition and PEFR. In AECOPD, MgSO4 exhibits enhanced early bronchodilator response when combined with other drugs, demonstrating significant efficacy, good safety, and tolerability at the prescribed dosage. [ABSTRACT FROM AUTHOR]

Airway mucus hypersecretion, a crucial pathological feature of chronic obstructive pulmonary disease (COPD), contributes to the initiation, progression, and exacerbation of this disease. As a macromolecular mucin, the secretory behaviour of Mucin5AC (MUC5AC) is highly dependent on a series of modifying and folding processes that occur in the endoplasmic reticulum (ER). In this study, we focused on the ER quality control protein KDEL receptor (KDELR) and demonstrated that KDELR2 and MUC5AC were colocalized in the airway epithelium of COPD patients and COPD model rats. In addition, knockdown of KDELR2 markedly reduced the expression of MUC5AC both in vivo and in vitro and knockdown of ATF6 further decreased the levels of KDELR2. Furthermore, pretreatment with 4μ8C, an IRE1α inhibitor, led to a partial reduction in the expression of KDELR2 and MUC5AC both in vivo and in vitro, which indicated the involvement of IRE1α/XBP‐1s in the upstream signalling cascade. Our study revealed that KDELR2 plays a crucial role in airway MUC5AC hypersecretion in COPD, which might be dependent on ATF6 and IRE1α/XBP‐1s upstream signalling. [ABSTRACT FROM AUTHOR]

Background: Cardiovascular diseases are some of the most prevalent chronic diseases that generate not only high social but also economic costs. It is becoming increasingly crucial to take into account inborn errors of immunity (IEIs, formerly known as primary immunodeficiencies (PIDs)) and secondary immunodeficiencies (SIDs) in the diagnostic and therapeutic management of cardiac patients. The number of diseases classified as IEIs is on the rise, with a current total of 485. It is essential to pay attention not only to already confirmed conditions but also to symptoms suggestive of immunodeficiencies. Objectives: The aim of this article is to present IEIs with cardiovascular symptoms that may cause or exacerbate cardiovascular disease, as well as diagnostic and therapeutic procedures. Results: It is becoming increasingly evident that immunodeficiencies can be responsible for certain cardiovascular conditions, their hastened progression, and difficulties in their control. Conclusions: Early detection of deficiencies improves not only the quality and longevity of patients, but also allows for better control of cardiovascular diseases and even prevention of their occurrence. [ABSTRACT FROM AUTHOR]