Annals of medicine最新文献

Background: Sarcopenic obesity (SO) is a multifactorial condition characterized by the coexistence of excess adiposity and reduced skeletal muscle mass and function. Its development reflects a complex interaction of metabolic, inflammatory, and endocrine mechanisms that disrupt the balance between anabolic and catabolic processes.

Main findings: Endocrine dysfunction is a major driver of the altered adipose-muscle crosstalk characteristic of SO. Hormonal imbalance amplifies mitochondrial dysfunction, oxidative stress, and chronic inflammation, leading to reduced muscle quality and increased visceral and intramuscular fat. Age-related hormonal decline, including reductions in testosterone and estrogens, growth hormone (GH), insulin-like growth factor 1, and thyroid hormones, together with increased catabolic activity of glucocorticoids and the renin-angiotensin-aldosterone system, as well as altered sympathoadrenal signaling, promotes insulin resistance, muscle catabolism, and fat accumulation. Beyond aging, endocrine diseases such as hypogonadism, GH deficiency, hypothyroidism, Cushing syndrome, hyperaldosteronism, and diabetes replicate many features of SO and serve as valuable models for investigating its underlying mechanisms.

Future directions: Emerging anabolic or anti-catabolic agents, such as Selective Androgen Receptor Modulators (SARMs), myostatin inhibitors, and ghrelin analogues, show promise but require further validation. Future research should explore endocrine disorders as experimental models of SO, focusing on the shared molecular and hormonal mechanisms that link fat accumulation and muscle loss. Finally, studying endocrine pathways in an integrated manner, rather than focusing on obesity and sarcopenia separately, may identify new hormonal targets for precision therapies aimed at restoring anabolic-catabolic balance and improving metabolic and functional outcomes in individuals with SO.

Background: Some intracranial aneurysms (IAs) still develop in-stent stenosis (ISS) even after successful pipeline embolization device (PED) implantation. ISS increases the risk of retreatment and ischemic complications, thereby affecting the long-term prognosis of IA patients. This study aims to identify predictors for ISS after PED treatment of IAs, and develop a nomogram for assessing individual risk.

Materials and methods: This analysis included unruptured IA patients treated with PEDs between April 2016 and October 2023 at three institutions. The patients were grouped into the training cohort and validation cohort according to the admission institution. Predictors were identified via least absolute shrinkage and selection operator analysis and multivariable regression analysis. A nomogram was then developed to predict ISS after PED implantation in the training cohort. The area under the receiver operating characteristic curve (AUC), calibration curves, and decision curve analysis (DCA) were used to evaluate the predictive accuracy and clinical value of the nomograms.

Results: A total of 1335 IA patients were included in this study (1049 in the training cohort and 286 in the validation cohort). A total of 139 (13.3%) and 41 (14.3%) patients developed ISS in the training cohort and validation cohort, respectively. A nomogram with five predictors (difference between the proximal and distal parent artery diameters, distal stent-to-vessel diameter ratio, overlapping devices, balloon angioplasty, and dissecting aneurysms) was developed via multivariate logistic regression analysis. AUCs of the nomogram in the training cohort and validation cohort were 0.836 (95%CI, 0.801-0.870) and 0.829 (95%CI, 0.770-0.888), respectively. Calibration curve and DCA analysis confirmed the utility and clinical applicability of this nomogram.

Conclusion: This nomogram showed high accuracy and clinical utility in predicting ISS after PED treatment, indicating that the nomogram can guide the identification of high-risk patients and the development of improved treatment strategies.

Objective: To investigate the clinical characteristics and impact of SMARCA4 mutations in patients with non-small cell lung cancer (NSCLC).

Methods: A total of 2,821 patients with NSCLC who underwent next-generation sequencing were retrospectively included. The frequency and types of SMARCA4 mutations and co-mutations were determined, and the clinical outcomes were assessed.

Results: SMARCA4 mutations were identified in 100 samples (3.54%), and 36% were missense mutations. The most frequent co-mutations were TP53 (67%) and EGFR (31%); 13% of SMARCA4 mutations occurred in samples carried EGFR and TP53 mutations. Notably, 63% SMARCA4 mutations did not present druggable driver mutations. SMARCA4 mutations were most prevalent in males and smokers. Patients with SMARCA4 mutant lung adenocarcinoma (LUAD) and EGFR mutations who received EGFR-tyrosine kinase inhibitors (EGFR-TKI) as first-line therapy had a lower objective response rate (ORR, 52.94%). In SMARCA4 mutation and EGFR wild-type (wt) NSCLC cohort who received first-line chemotherapy, age (hazard ratio [HR], 3.090; p = 0.026) and performance score (HR, 5.848; p = 0.045) were identified as independent predictors of progression-free survival (PFS). Conversely, brain metastasis was an independent predictor of superior overall survival (HR, 0.188; p = 0.011). The patients with EGFR wt and SMARCA4 mutant Stage IV LUAD who received chemotherapy plus anti-angiogenic therapy significantly improved median PFS compared to chemotherapy alone (p = 0.04).

Conclusions: SMARCA4 mutations were predominantly males and smokers in NSCLC. SMARCA4 mutations conferred a poorer response for EGFR-mutant LUAD subgroups who received EGFR-TKIs. Additionally, chemotherapy plus anti-angiogenesis as first-line therapy may be more effective for Stage IV-SMARCA4 mutant LUAD with EGFR wt.

Background: Post-intensive care syndrome (PICS) is a post-discharge complication from the intensive care unit (ICU) that manifests as a range of physical, cognitive, and psychological impairments for patients. Given the growing number of ICU survivors and the vital role of this syndrome in identifying individuals at risk of deterioration after ICU discharge, we conducted a systematic review and meta-analysis to assess the prevalence and incidence of PICS.

Method: Between January 1, 2010, and October 5, 2024, a thorough search was conducted across the Web of Science, PubMed, Scopus, Embase, Cochrane Library, and CINAHL databases. Cross-sectional and cohort studies were included. The prevalence and incidence of PICS, as determined by any assessment method, were the primary study outcomes. PICS was defined according to the criteria used in each primary study. A meta-analysis was performed using a random-effects model. Meta-regression analysis was employed to investigate the impact of distinct follow-up durations on the reported prevalence and incidence. The JBI critical appraisal tool for prevalence studies was used to assess the risk of bias in the included studies.

Results: This systematic review and meta-analysis synthesised data from 34 studies involving 6230 participants. The pooled prevalence and incidence of PICS were 60.3% (95% CI: 48.5-72.1) and 52.4% (95% CI: 47.6-57.2), respectively. The I² statistic for heterogeneity in the included prevalence and incidence studies was 98.67% and 81.23%, respectively. Subgroup analyses by country, cutoff definition, and underlying participant disease revealed a substantial reduction in heterogeneity. Only the use of a cutoff substantially reduced heterogeneity in reported incidence across studies.

Conclusion: This systematic review and meta-analysis demonstrate a notable prevalence and incidence of PICS among ICU survivors. These findings highlight the need for early detection of at-risk individuals and the development of evidence-based approaches to monitor and address impairments related to PICS.

Background: Chimeric antigen receptor (CAR) -T cell therapy has emerged as a promising approach for treating severe autoimmune diseases (AIDs), offering distinct advantages over conventional immunosuppressive therapies. This review examines recent advancements in both autologous and allogeneic CAR-T platforms for AIDs.

Methods: We analyzed preclinical and clinical evidence regarding CAR-T therapies. These therapies target signaling molecules across various cells in the myeloid and lymphoid lineages, addressing autoimmune pathologies across dermatological, neurological, gastrointestinal, and hematological systems.

Results: Diversified CAR-T technological innovations have been developed. CAR-T therapy achieves remarkable efficacy in various AID by precisely eliminating pathogenic cells and facilitating a systemic immune reset, thereby maintaining a favorable balance between therapeutic benefit and safety.

Conclusion: CAR-T cell therapy represents a revolutionary therapeutic strategy for the management of refractory AIDs. Addressing current challenges will further promote its clinical translation and expand its application in the treatment of AIDs.

Background: Patients with both acute myocardial infarction (AMI) and chronic kidney disease (CKD) face a markedly poor prognosis, a key driver of which is insulin resistance (IR). This study aims to systematically evaluate and compare the predictive performance of four commonly used IR indices for major adverse cardiovascular events (MACE), and to assess their incremental value over the GRACE score in this patient group.

Methods: This retrospective cohort study analyzed 1,803 patients with AMI and CKD. Multivariable Cox regression determined associations between IR indices and MACE. Predictive performance was evaluated using C-statistics, continuous net reclassification improvement (cNRI), and integrated discrimination improvement (IDI).

Results: During a median follow-up of 28.2 months, 462 MACE occurred. Patients with MACE were older, had higher female proportion, elevated GRACE score, and increased diabetes prevalence (all p < 0.05). the triglyceride-glucose (TyG) index and the atherogenic index of plasma (AIP) demonstrated linear associations with MACE risk, whereas TyG-body mass index (TyG-BMI) and metabolic score for insulin resistance (METS-IR) exhibited U-shaped nonlinear relationships (p < 0.001). The Area Under the Curve (AUCs) for MACE prediction were: TyG index 0.62, AIP 0.57, TyG-BMI 0.58, and METS-IR 0.56. Incorporating IR indices significantly enhanced the GRACE score's predictive capacity, with TyG index providing the greatest incremental improvement (cNRI = 0.137, IDI = 0.03).

Conclusion: IR indices predict outcomes in patients with AMI and CKD and enhance GRACE score prediction, with TyG index demonstrating superior performance.