Background The intestinal-liver axis is associated with various liver diseases. Here, we verified the role of the gut microbiota and macrophage activation in the progression of pyrrolizidine alkaloids-induced hepatic sinusoidal obstruction syndrome (PA-HSOS), and explored the possible mechanisms and new treatment options.
Objective : To study the incidence of cardiovascular events and related risk factors in diabetes and hypertension patients.Methods: A total of 3,173 patients with diabetes, 35,161 with hypertension, 5,261 with both hypertension and diabetes, and 50,320 without hypertension and diabetes from the KaiLuan study cohort were enrolled.Multivariable Cox proportional hazards regression model was used to assess relative risk for cardiovascular and all-cause mortality events.Results: Compared to the diabetes group, blood pressure, body mass index, serum creatinine, high-density lipoprotein cholesterol, uric acid, and the proportion of males were higher while the average levels of total cholesterol, triglyceride, fasting blood glucose, and high-sensitivity C-reactive protein were lower in the hypertension group (P < 0.05).During a 48-month mean follow-up, a total of 1,863 cardiovascular events were recorded.After adjusted for other traditional cardiovascular risk factors, compared with subjects without hypertension and diabetes, the hazard ratio (95% CI) in patients with diabetes, hypertension, and diabetes plus hypertension was 2. 773 (2.225-3.455),2.571 (2.290-2.887),and 3.975 (3.390-4.662),respectively, for cardiovascular events; 3.040 (1.976-4.677),1.965 (1.528-2.528),and 3.797 (2.740-5.261)for myocardial infarction; 3.026 (2.281-4.015),2. 629 (2.256-3.063),and 4.383 (3.569-5.383)for cerebral infarction; 1.927 (1.058-3.508),3.733 (2.961-4.705),and 3.977 (2.763-5.723)for cerebral hemorrhage; and 1.988 (1.584-2.494),1.462 (1.305-1.639),and 2.411 (2.035-2.856)for all-cause mortality. Conclusion:Diabetes and hypertension are independent risk factors for cardiovascular events.Patients with both diabetes and hypertension have the highest incidence of myocardial infarction, cerebral hemorrhage, and all-cause mortality.
Alterations in body compositions are related to poor outcomes and the presence of complications in cirrhosis. However, no predictive tools combining all these anthropometric parameters are applicable in the clinical setting. We aimed to clarify the potential utility of body compositions and develop a nomogram incorporating any independent factor for prognosticating long-term mortality in cirrhosis.A total of 414 patients were randomized into primary (n = 274) and validation (n = 140) cohorts. X-tile was performed to identify optimal cut points for stratifying participants. Multivariate Cox regression was performed, and nomogram incorporating body compositions were generated. The utility of developed models was evaluated by Harrell concordance index (C-index), calibration curve, and decision curve analysis (DCA).Stratifying by X-tilederived cut points, low skeletal muscle index (myopenia), high intramuscular adipose tissue content (myosteatosis), and the ratio of high visceral to subcutaneous adipose tissue area (adiposity) was independently associated with 3-year mortality. A sex-stratified nomogram incorporating anthropometric indices and clinical factors resulted in moderate discriminative accuracy, with a C-index of 0.787 (95% CI, 0.736-0.838) and 0.789 (95% CI, 0.727-0.851) in males and females, respectively. The calibration curve showed predictive survival corresponding optimally with the actual outcomes. Our models were feasible in the clinical settings based on DCA. Similar results were observed in the validation cohort. Additionally, participants could be classified into 3 distinct risk groups by the nomogram.Our proposed nomogram embedding body compositions rendered an individualized predictive tool for long-term mortality in cirrhosis.
No tailored model incorporating physical frailty for 2-year mortality in cirrhosis is available for practitioners in general practice. Thus we aimed to develop a model based on laboratory results and physical frailty allowing clinicians for stratifying cirrhotics by using individual estimate.One hundred and thirteen cases were assigned to the primary cohort, and all other 76 patients were regarded as the validation cohort. Multivariate Cox regression was performed, and a nomogram including five-meter gait speed (5MGS) were generated. The performance of the proposed model was assessed by C-index, calibration curve, and decision curve analysis (DCA).On multivariate analysis, the Model for End-Stage Liver Disease-Sodium, albumin and 5MGS were independent predictors for 2-year mortality in cirrhosis. A nomogram incorporating all these parameters achieved a C-index of 0.804 (95%CI, 0.731-0.877). The calibration curve implied optimal correspondence between the predicted survival and actual outcomes. Our model is useful in the clinical settings based on DCA. Similar results were observed in the validation cohort with a C-index of 0.796 (95%CI, 0.689-0.899). Moreover, 5MGS, as a surrogate of physical performance, significantly correlated with multiple domains of general frailty according to Frailty Index (our published data), including instrumental activities of daily living, self-reported health, social activity and falls.In conclusion, the nomogram incorporating 5MGS may represent an individualized tool for predicting mortality in cirrhosis for primary care physicians.
While hepatocellular carcinoma (HCC) represents a highly heterogeneous disease with variable oncogenesis mechanisms and biological features, little is understood about differences in distant metastasis (DM) and prognosis between early-onset and late-onset HCC. This study defined early-onset disease as cancer diagnosed at age younger than 50 years and aimed to present a comprehensive analysis to characterize these disparities based on age.
The COVID-19 pandemic has caused significant global public health challenges, and impacted HIV testing and reporting worldwide. We aimed to estimate the impact of COVID-19 polices on identifying HIV/AIDS cases in China from 2020 to 2022.
Abstract We aimed to explore factors associated with prognosis in patients with metastatic small bowel adenocarcinoma (SBA) as well as to develop and validate nomograms to predict overall survival (OS) and cancer-specific survival (CSS). Relevant information of patients diagnosed between 2004 and 2016 was extracted from the Surveillance, Epidemiology, and End Results (SEER) database. Nomograms for predicting 1- and 3-year OS and CSS were established with potential risk factors screened from multivariate cox regression analysis. The discrimination and accuracy of the nomograms were assessed by concordance index (C-index), calibration plots, and the area under receiver operating characteristic curve (AUC). In total, 373 SBA patients with M1 category were enrolled. Multivariate analysis revealed that age, size and grade of primary tumor, primary tumor surgery, and chemotherapy were significant variables associated with OS and CSS. The C-index values of the nomogram for OS were 0.715 and 0.687 in the training and validation cohorts, respectively. For CSS, it was 0.711 and 0.690, respectively. Through AUC, decision curve analysis (DCA) and calibration plots, the nomograms displayed satisfactory prognostic predicted ability and clinical application both in the OS and CSS. Our models could be served as a reliable tool for prognostic evaluation of patients with metastatic SBA, which are favorable in facilitating individualized survival predictions and clinical decision-making.
Abstract Background & Aims An elevated neutrophil‐to‐lymphocyte ratio (NLR) has received attention as a prognostic surrogate across chronic liver diseases. However, an exact threshold has not been fully elucidated. Methods A total number of 589 patients with cirrhosis (LC) were included. The value of NLR was calculated and its optimal cut‐off was initially determined by X‐tile program. Independent predictors of 90‐day mortality were identified with Cox regression model. The Kaplan‐Meier method was used to generate survival curves. To reduce influences of selection bias and possible confounders, a 1:2 propensity score matching (PSM) was performed. Results The X‐tile indicated that the difference in survival was most significant for NLR more than 8.9. Serum NLR > 8.9 was an independent indicator in the entire cohort and PSM subset (HR 4.268, 95% CI 2.211‐8.238, P < .001; HR 4.209, 95% CI 1.448‐12.238, P = .008 respectively). Subgroup analysis showed that NLR > 8.9 was an independent risk factor of 90‐day mortality regardless of age, gender, CTP or MELD score. Conclusions The value of NLR more than 8.9 is a feasible cut‐off across clinical settings among applicable population. The adding of NLR to other conventional predictive systems has the potential to provide incremental value without extra economic cost.
Ferroptosis is an iron- and lipotoxicity-dependent form of regulated cell death (RCD). It is morphologically and biochemically distinct from characteristics of other cell death. This modality has been intensively investigated in recent years due to its involvement in a wide array of pathologies, including cancer, neurodegenerative diseases, and acute kidney injury. Dysregulation of ferroptosis has also been linked to various liver diseases and its modification may provide a hopeful and attractive therapeutic concept. Indeed, targeting ferroptosis may prevent the pathophysiological progression of several liver diseases, such as hemochromatosis, nonalcoholic steatohepatitis, and ethanol-induced liver injury. On the contrary, enhancing ferroptosis may promote sorafenib-induced ferroptosis and pave the way for combination therapy in hepatocellular carcinoma. Glutathione peroxidase 4 (GPx4) and system xc- have been identified as key players to mediate ferroptosis pathway. More recently diverse signaling pathways have also been observed. The connection between ferroptosis and other forms of RCD is intricate and compelling, where discoveries in this field advance our understanding of cell survival and fate. In this review, we summarize the central molecular machinery of ferroptosis, describe the role of ferroptosis in non-cancer hepatic disease conditions and discuss the potential to manipulate ferroptosis as a therapeutic strategy.
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