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Frontiers in Immunology 2024Exacerbations of chronic obstructive pulmonary disease (COPD) increase mortality risk and can lead to accelerated loss of lung function. The increased inflammatory...
INTRODUCTION
Exacerbations of chronic obstructive pulmonary disease (COPD) increase mortality risk and can lead to accelerated loss of lung function. The increased inflammatory response during exacerbations contributes to worsening of airflow limitation, but whether it also impacts epithelial repair is unclear. Therefore, we studied the effect of the soluble factor micro-environment during COPD exacerbations on epithelial repair using an exacerbation cocktail (EC), composed of four factors that are increased in COPD lungs during exacerbations (IL-1β, IL-6, IL-8, TNF-α).
METHODS
Mouse organoids (primary CD31-CD45-Epcam+ cells co-cultured with CCL206 fibroblasts) were used to study epithelial progenitor behavior. Mature epithelial cell responses were evaluated using mouse precision cut lung slices (PCLS). The expression of epithelial supportive factors was assessed in CCL206 fibroblasts and primary human lung fibroblasts.
RESULTS
EC exposure increased the number and size of organoids formed, and upregulated , and expression in day 14 organoids. In PCLS, EC imparted no effect on epithelial marker expression. Pre-treatment of CCL206 fibroblasts with EC was sufficient to increase organoid formation. Additionally, the expression of , and was increased in CCL206 fibroblasts from EC treated organoids, but these factors individually did not affect organoid formation or size. However, TGF-α downregulated expression and upregulated expression in day 14 organoids.
CONCLUSIONS
EC exposure stimulates organoid formation and growth, but it alters epithelial differentiation. EC changes the epithelial progenitor support function of fibroblasts which contributes to observed effects on epithelial progenitors.
Topics: Animals; Pulmonary Disease, Chronic Obstructive; Humans; Mice; Fibroblasts; Epithelial Cells; Organoids; Cytokines; Lung; Cells, Cultured; Disease Progression; Respiratory Mucosa; Mice, Inbred C57BL
PubMed: 38911863
DOI: 10.3389/fimmu.2024.1346491 -
Frontiers in Immunology 2024The study aimed to analyze the efficacy and safety of PD-1 inhibitors plus chemotherapy with or without endostatin for stage IV lung squamous cell carcinoma (LUSC).
BACKGROUD
The study aimed to analyze the efficacy and safety of PD-1 inhibitors plus chemotherapy with or without endostatin for stage IV lung squamous cell carcinoma (LUSC).
METHODS
A total of 219 patients with stage IV LUSC were included. 120 received PD-1 inhibitors plus chemotherapy with or without endostatin (IC ± A), of which 39 received endostatin (IC+A) and 81 did not receive endostatin (IC-A). 99 received chemotherapy with or without endostatin (C ± A). Endpoints included overall survival (OS), progression-free survival (PFS), adverse events (AEs), and immune-related adverse events (irAEs).
RESULTS
The median PFS in the IC ± A group versus the C ± A group was 8 and 4 months (P < 0.001), and the median OS was 17 and 9 months (P < 0.001). There was no significant difference in any grade AEs between the IC ± A and C ± A groups (P > 0.05). The median PFS in the IC+A group versus the IC-A group was 11 and 7 months (P = 0.024), and the median OS was 34 and 15 months (P = 0.01). There was no significant difference between the IC+A group and the IC-A group for all grade AEs and irAEs (P > 0.05). The subgroup analysis showed that patients with LIPI = 0 had significant OS and PFS benefits in IC+A group, while for patients with LIPI = 1-2, there was no significant difference in OS and PFS benefits between the IC+A group and IC-A group.
CONCLUSIONS
PD-1 inhibitors plus chemotherapy with endostatin might be first-line treatment for patients with stage IV LUSC.
Topics: Humans; Endostatins; Male; Female; Lung Neoplasms; Middle Aged; Retrospective Studies; Aged; Immune Checkpoint Inhibitors; Antineoplastic Combined Chemotherapy Protocols; Neoplasm Staging; Carcinoma, Squamous Cell; Adult; Programmed Cell Death 1 Receptor; Treatment Outcome
PubMed: 38911862
DOI: 10.3389/fimmu.2024.1413204 -
Frontiers in Immunology 2024To investigate the treatment response and toxicity of the combination of induction chemotherapy (IC) and PD-1 inhibitor in locally advanced nasopharyngeal carcinoma...
PURPOSE
To investigate the treatment response and toxicity of the combination of induction chemotherapy (IC) and PD-1 inhibitor in locally advanced nasopharyngeal carcinoma (LANPC).
METHODS
Patients with stage III-IVA NPC who received IC or IC + PD-1 inhibitor were included. The chi-square test and multivariate logistic regression analysis were used for statistical analysis.
RESULTS
A total of 225 patients were identified, including 193 (85.8%) and 32 (14.2%) who received IC alone and IC + PD-1 inhibitor, respectively. The addition of PD-1 inhibitor to IC significantly improved the tumor response than those treated with IC alone. The complete response (CR), partial response, stable disease, and progressive disease rates of 4.7% vs. 31.3%, 69.4% vs. 62.5%, 24.9% vs. 6.3%, and 1.0% vs. 0% in patients receiving IC alone and IC + PD-1 inhibitor, respectively (P<0.001). The results of the multivariate logistic regression showed that receiving PD-1 inhibitor was an independent predictor influencing the CR rate of patients (odds ratio 9.814, P<0.001). The most common toxicity by using IC and PD-1 inhibitor was hematological toxicity. In terms of non-hematological toxicity, 7 (21.9%) patients experienced thyroid dysfunction and all of them were hyperthyroidism. No grade 5 toxicities were found. In those who received IC and PD-1 inhibitor, the one-year locoregional recurrence-free survival, distant metastasis-free survival, disease-free survival, and overall survival were 100%, 96.9%, 96.9%, and 100%, respectively.
CONCLUSION
The addition of PD-1 inhibitor to IC has promise as an effective treatment approach for LANPC. More studies are expected to provide further insights into the optimal use of this treatment strategy, paving the way for more personalized and effective treatment options for patients with LANPC.
Topics: Humans; Male; Female; Nasopharyngeal Carcinoma; Middle Aged; Induction Chemotherapy; Adult; Nasopharyngeal Neoplasms; Aged; Immune Checkpoint Inhibitors; Antineoplastic Combined Chemotherapy Protocols; Programmed Cell Death 1 Receptor; Treatment Outcome; Neoplasm Staging; Young Adult; Retrospective Studies
PubMed: 38911859
DOI: 10.3389/fimmu.2024.1415246 -
Frontiers in Immunology 2024Hypereosinophilic Syndrome (HES) is a rare disorder characterized by persistent elevation of eosinophils, leading to multi-organ infiltration and damage. Eosinophilic...
INTRODUCTION
Hypereosinophilic Syndrome (HES) is a rare disorder characterized by persistent elevation of eosinophils, leading to multi-organ infiltration and damage. Eosinophilic Myocarditis (EM) is one of its severe complications contributing significantly to morbidity and mortality. Herein, we describe the diagnostic and therapeutic challenges of EM, emphasizing the significance of early recognition and multidisciplinary management.
CASE PRESENTATION
A 51-year-old female with a history of EM, heart failure, and peripheral eosinophilia presented with NYHA class 3b symptoms. Laboratory findings revealed elevated peripheral eosinophil count, NT-Pro BNP, and characteristic electrocardiogram abnormalities. Imaging studies confirmed biventricular thrombi and myocardial abnormalities consistent with EM. Treatment involved Solu-Medrol for HES and heparin for ventricular thrombi, leading to initial clinical improvement. However, refractory heart failure necessitated urgent heart transplantation.
DISCUSSION
EM, an under-recognized complication of HES, poses diagnostic and management challenges. Management includes standard heart failure treatments, steroids, and emerging therapies like Mepolizumab. Early diagnosis and aggressive management are pivotal for improving outcomes in this rare and potentially fatal condition.
CONCLUSION
Advancements in the detection of complications, surgical management, and therapeutic options have improved outcomes in HES. Ongoing research is essential to further understand and address the diagnostic and therapeutic challenges of HES and EM.
Topics: Humans; Hypereosinophilic Syndrome; Myocarditis; Female; Middle Aged; Heart Transplantation; Heart Failure; Eosinophilia
PubMed: 38911849
DOI: 10.3389/fimmu.2024.1418665 -
Annals of Surgery Open : Perspectives... Jun 2024To determine whether certain patients are vulnerable to errant triage decisions immediately after major surgery and whether there are unique sociodemographic phenotypes...
OBJECTIVE
To determine whether certain patients are vulnerable to errant triage decisions immediately after major surgery and whether there are unique sociodemographic phenotypes within overtriaged and undertriaged cohorts.
BACKGROUND
In a fair system, overtriage of low-acuity patients to intensive care units (ICUs) and undertriage of high-acuity patients to general wards would affect all sociodemographic subgroups equally.
METHODS
This multicenter, longitudinal cohort study of hospital admissions immediately after major surgery compared hospital mortality and value of care (risk-adjusted mortality/total costs) across 4 cohorts: overtriage (N = 660), risk-matched overtriage controls admitted to general wards (N = 3077), undertriage (N = 2335), and risk-matched undertriage controls admitted to ICUs (N = 4774). K-means clustering identified sociodemographic phenotypes within overtriage and undertriage cohorts.
RESULTS
Compared with controls, overtriaged admissions had a predominance of male patients (56.2% vs 43.1%, < 0.001) and commercial insurance (6.4% vs 2.5%, < 0.001); undertriaged admissions had a predominance of Black patients (28.4% vs 24.4%, < 0.001) and greater socioeconomic deprivation. Overtriage was associated with increased total direct costs [$16.2K ($11.4K-$23.5K) vs $14.1K ($9.1K-$20.7K), < 0.001] and low value of care; undertriage was associated with increased hospital mortality (1.5% vs 0.7%, = 0.002) and hospice care (2.2% vs 0.6%, < 0.001) and low value of care. Unique sociodemographic phenotypes within both overtriage and undertriage cohorts had similar outcomes and value of care, suggesting that triage decisions, rather than patient characteristics, drive outcomes and value of care.
CONCLUSIONS
Postoperative triage decisions should ensure equality across sociodemographic groups by anchoring triage decisions to objective patient acuity assessments, circumventing cognitive shortcuts and mitigating bias.
PubMed: 38911666
DOI: 10.1097/AS9.0000000000000429 -
Annals of Surgery Open : Perspectives... Jun 2024Postoperative pulmonary embolism (PE) is a rare but potentially life-threatening complication, which can be treated with extracorporeal membrane oxygenation (ECMO)...
OBJECTIVE
Postoperative pulmonary embolism (PE) is a rare but potentially life-threatening complication, which can be treated with extracorporeal membrane oxygenation (ECMO) therapy, a novel therapy option for acute cardiorespiratory failure. We postulate that hospitals with ECMO availability have more experienced staff, technical capabilities, and expertise in treating cardiorespiratory failure.
DESIGN
A retrospective analysis of surgical procedures in Germany between 2012 and 2019 was performed using hospital billing data. High-risk surgical procedures for postoperative PE were analyzed according to the availability of and expertise in ECMO therapy and its effect on outcome, regardless of whether ECMO was used in patients with PE.
METHODS
Descriptive, univariate, and multivariate analyses were applied to identify possible associations and correct for confounding factors (complications, complication management, and mortality).
RESULTS
A total of 13,976,606 surgical procedures were analyzed, of which 2,407,805 were defined as high-risk surgeries. The overall failure to rescue (FtR) rate was 24.4% and increased significantly with patient age, as well as type of surgery. The availability of and experience in ECMO therapy (defined as at least 20 ECMO applications per year; ECMO centers) are associated with a significantly reduced FtR in patients with PE after high-risk surgical procedures. In a multivariate analysis, the odds ratio (OR) for FtR after postoperative PE was significantly lower in ECMO centers (OR, 0.75 [0.70-0.81], < 0.001).
CONCLUSIONS
The availability of and expertise in ECMO therapy lead to a significantly reduced FtR rate of postoperative PE. This improved outcome is independent of the use of ECMO in these patients.
PubMed: 38911642
DOI: 10.1097/AS9.0000000000000416 -
Annals of Surgery Open : Perspectives... Jun 2024To compare long-term outcomes after laparoscopic lavage with resection surgery for perforated diverticulitis, Hinchey grade III as practiced in Sweden for 3 years.
OBJECTIVE
To compare long-term outcomes after laparoscopic lavage with resection surgery for perforated diverticulitis, Hinchey grade III as practiced in Sweden for 3 years.
BACKGROUND
Laparoscopic lavage has been studied in 3 randomized controlled trials. Long-term results indicate that additional surgery and a remaining stoma are less common after lavage compared with resection, but data from routine care and larger cohorts are needed to get a more complete picture.
METHODS
LapLav is a national cohort study with nearly complete coverage of all patients operated in Sweden between 2016 and 2018. The cohort was retrieved from the national patient register by a definition based on the Classification of Diseases and Related Health Problems-10 code plus the surgical procedural code. All medical records have been reviewed and data retrieved in addition to registry data. Propensity score with inverse probability weighting was used to balance the 2 groups, that is, laparoscopic lavage resection surgery.
RESULTS
Before the propensity score was applied, the cohort consisted of 499 patients. Additional surgery was more common in the resection group [odds ratio, 0.714; 95% confidence interval (CI) = 0.529-0.962; = 0.0271]. Mortality did not differ between the groups (hazard ratio, 1.20; 95% CI = 0.69-2.07; = 0.516). In the lavage group, 27% of patients went on to have resection surgery.
CONCLUSIONS
In Swedish routine care, laparoscopic lavage was feasible and safe for the surgical treatment of perforated diverticulitis, Hinchey grade III. Our results indicate that laparoscopic lavage can be used as a first-choice treatment.
PubMed: 38911640
DOI: 10.1097/AS9.0000000000000433 -
Annals of Surgery Open : Perspectives... Jun 2024This study, examining literature up to December 2023, aims to comprehensively assess surgical care for incarcerated individuals, identifying crucial knowledge gaps for... (Review)
Review
OBJECTIVE
This study, examining literature up to December 2023, aims to comprehensively assess surgical care for incarcerated individuals, identifying crucial knowledge gaps for informing future health services research and interventions.
BACKGROUND
The US prison system detains around 2 million individuals, mainly young, indigent males from ethnic and racial minorities. The constitutional right to healthcare does not protect this population from unique health challenges and disparities. The scarcity of literature on surgical care necessitates a systematic review to stimulate research, improve care quality, and address health issues within this marginalized community.
METHODS
A systematic review, pre-registered with the International Prospective Register of Systematic Reviews (CRD42023454782), involved searches in PubMed, Embase, and Web of Science. Original research on surgical care for incarcerated individuals was included, excluding case reports/series (<10 patients), abstracts, and studies involving prisoners of war, plastic surgeries for recidivism reduction, transplants using organs from incarcerated individuals, and nonconsensual surgical sterilization.
RESULTS
Out of 8209 studies screened, 118 met inclusion criteria, with 17 studies from 16 distinct cohorts reporting on surgical care. Predominantly focusing on orthopedic surgeries, supplemented by studies in emergency general, burns, ophthalmology, and kidney transplantation, the review identified delayed hospital presentations, a high incidence of complex cases, and low postoperative follow-up rates. Notable complications, such as nonfusion and postarthroplasty infections, were more prevalent in incarcerated individuals compared with nonincarcerated individuals. Trauma-related mortality rates were similar, despite lower intraabdominal injuries following penetrating abdominal injuries in incarcerated patients.
CONCLUSION
While some evidence suggests inferior surgical care in incarcerated patients, the limited quality of available studies underscores the urgency of addressing knowledge gaps through future research. This is crucial for patients, clinicians, and policymakers aiming to enhance care quality for a population at risk of surgical complications during incarceration and postrelease.
PubMed: 38911628
DOI: 10.1097/AS9.0000000000000434 -
Annals of Surgery Open : Perspectives... Jun 2024The aim of this observational study was to analyze trends in the incidence, mortality, and disability-adjusted life years (DALYs) of benign gallbladder and biliary...
OBJECTIVE
The aim of this observational study was to analyze trends in the incidence, mortality, and disability-adjusted life years (DALYs) of benign gallbladder and biliary diseases across high-income countries between 1990 and 2019.
BACKGROUND
Benign gallbladder and biliary diseases place a substantial burden on healthcare systems in high-income countries. Accurate characterization of the disease burden may help optimize healthcare policy and resource distribution.
MATERIALS AND METHODS
Age-standardized incidence rates (ASIRs), age-standardized mortality rates (ASMRs), and DALYs data for gallbladder and biliary diseases in males and females were extracted from the 2019 Global Burden of Disease (GBD) study. A mortality-incidence index (MII) was also calculated. Joinpoint regression analysis was performed.
RESULTS
The median ASIRs across the European Union 15+ countries in 2019 were 758/100,000 for females and 282/100,000 for males. Between 1990 and 2019 the median percentage change in ASIR was +2.49% for females and +1.07% for males. The median ASMRs in 2019 were 1.22/100,000 for females and 1.49/100,000 for males with a median percentage change over the observation period of -21.93% and -23.01%, respectively. In 2019, the median DALYs was 65/100,000 for females and 37/100,000 among males, with comparable percentage decreases over the observation period of -21.27% and -19.23%, respectively.
CONCLUSIONS
International variation in lifestyle factors, diagnostic and management strategies likely account for national and sex disparities. This study highlights the importance of ongoing clinical efforts to optimize treatment pathways for gallbladder and biliary diseases, particularly in the provision of emergency surgical services and efforts to address population risk factors.
PubMed: 38911626
DOI: 10.1097/AS9.0000000000000453 -
Annals of Surgery Open : Perspectives... Jun 2024To assess the added value of 3-dimensional (3D) vision, including high definition (HD) technology, in laparoscopic surgery in terms of surgeon preference and clinical...
OBJECTIVE
To assess the added value of 3-dimensional (3D) vision, including high definition (HD) technology, in laparoscopic surgery in terms of surgeon preference and clinical outcome.
BACKGROUND
The use of 3D vision in laparoscopic surgery has been suggested to improve surgical performance. However, the added value of 3D vision remains unclear as a systematic review of randomized controlled trials (RCTs) comparing 3D vision including HD technology in laparoscopic surgery is currently lacking.
METHODS
A systematic review was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) guidelines with a literature search up to May 2023 using PubMed and Embase (PROSPERO, CRD42021290426). We included RCTs comparing 3D versus 2-dimensional (2D) vision in laparoscopic surgery. The primary outcome was operative time. Meta-analyses were performed using the random effects model to estimate the pooled effect size expressed in standard mean difference (SMD) with corresponding 95% confidence intervals (CIs). The level of evidence and quality was assessed according to the Cochrane risk of bias tool.
RESULTS
Overall, 25 RCTs with 3003 patients were included. Operative time was reduced by 3D vision (-8.0%; SMD, -0.22; 95% CI, -0.37 to -0.06; = 0.007; n = 3003; 24 studies; = 75%) compared to 2D vision. This benefit was mostly seen in bariatric surgery (-16.3%; 95% CI, -1.28 to -0.21; = 0.006; 2 studies; n = 58; = 0%) and general surgery (-6.7%; 95% CI, -0.34 to -0.01; = 0.036; 9 studies; n = 1056; = 41%). Blood loss was nonsignificantly reduced by 3D vision (SMD, -0.33; 95% CI, -0.68 to 0.017; = 0.060; n = 1830; = 92%). No differences in the rates of morbidity (14.9% vs 13.5%, = 0.644), mortality (0% vs 0%), conversion (0.8% vs 0.9%, = 0.898), and hospital stay (9.6 vs 10.5 days, = 0.078) were found between 3D and 2D vision. In 15 RCTs that reported on surgeon preference, 13 (87%) reported that the majority of surgeons favored 3D vision.
CONCLUSIONS
Across 25 RCTs, this systematic review and meta-analysis demonstrated shorter operative time with 3D vision in laparoscopic surgery, without differences in other outcomes. The majority of surgeons participating in the RCTs reported in favor of 3D vision.
PubMed: 38911624
DOI: 10.1097/AS9.0000000000000415