- 作者列表："Murphy, Susan L.","Richardson, James K.","Blackwood, Jennifer","Martinez, Beanna","Tapper, Elliot B.
Background Frailty is common in cirrhosis and associated with mortality, hospitalization, and reduced quality of life. Interventions aimed at forestalling frailty are limited by a lack of understanding of underlying physiologic deficits. Aims This study’s aim was to examine contributions of discrete sensorimotor and neurocognitive capacities to conventional frailty measures of unipedal stance time, chair stands, and grip strength. Methods This cross-sectional study enrolled 119 outpatients with cirrhosis (50% female, aged 62.9 ± 7.3 years). Capacities included sensory (lower limb sensation and visual contrast), neurocognitive (Number Connection Tests A and B, simple and recognition reaction time), and muscular (hip/core strength determined by lateral plank time (LPT)). Bivariate analyses and linear regression models were performed to identify significant contributors to each frailty measure. Results The average performance was 9.8 ± 3.9 chair stands, 12.7 s ±9.9 unipedal stance time, and 60.3 ± 25.6 lb grip strength. In multivariate models, factors explained 40% of variance in unipedal stance and 43% of variance in chair stands. The LPT was most strongly associated with unipedal stance and chair stands. Grip strength was associated with LPT, but did not have physiologic predictors. Conclusions Clinically useful measures of frailty in adults with cirrhosis can be explained by disease severity but also deficits in strength and neurocognitive function. Recognition reaction time, a novel measure in cirrhosis, had a significant contribution to frailty. These findings have implications for frailty assessment and suggest that the optimal rehabilitation approach to frailty targets neurocognitive function in addition to strengthening.
背景虚弱在肝硬化中很常见，与死亡率、住院和生活质量降低有关。旨在预防虚弱的干预措施因缺乏对潜在生理缺陷的理解而受到限制。目的本研究的目的是检查离散感觉运动和神经认知能力对单足站立时间、椅子站立和握力的常规虚弱测量的贡献。方法本横断面研究纳入 119 例门诊肝硬化患者 (女性 50% 例，年龄 62.9 ± 7.3 岁)。能力包括感觉 (下肢感觉和视觉对比) 、神经认知 (数字连接测试 A 和 B 、简单和识别反应时间) 、和肌肉 (由外侧板时间 (LPT) 决定的臀部/核心力量)。进行双变量分析和线性回归模型，以确定每个虚弱指标的显著贡献因素。结果平均性能为 9.8 ± 3.9 椅架，12.7 s ± 9.9 单足站立时间，60.3 ± 25.6 lb 握力。在多变量模型中，因素解释了单足站姿 40% 的方差和椅架 43% 的方差。LPT 与单足姿势和椅架的相关性最强。握力与 LPT 相关，但没有生理预测因子。结论成人肝硬化患者虚弱的临床有用指标可以用疾病严重程度来解释，但也可以用力量和神经认知功能缺陷来解释。识别反应时间是肝硬化的一种新指标，对虚弱有显著贡献。这些发现对虚弱评估有影响，表明虚弱的最佳康复方法除了加强外，还针对神经认知功能。
METHODS:BACKGROUND:Opioids are often prescribed for pain in cirrhosis and may increase the risk of hepatic encephalopathy (HE). AIMS:To assess the association between opioids and HE in patients with well-compensated cirrhosis. METHODS:We used the IQVIA PharMetrics (Durham, NC) database to identify patients aged 18-64 years with cirrhosis. We excluded patients with any decompensation event from 1 year before cirrhosis diagnosis to 6 months after cirrhosis diagnosis. Over the 6 months after cirrhosis diagnosis, we determined the duration of continuous opioid use and classified use into short term (1-89 days) and chronic (90-180 days). We assessed whether patients developed HE over the subsequent year (ie 6-18 months after cirrhosis diagnosis). We used a landmark analysis and performed multivariable Cox proportional hazards regression to assess associations between opioid use and HE, adjusting for relevant confounders. RESULTS:The cohort included 6451 patients with compensated cirrhosis, of whom 23.3% and 4.7% had short-term and chronic opioid prescriptions respectively. Over the subsequent year, HE occurred in 6.3% patients with chronic opioid prescriptions, 5.0% with short-term opioid prescriptions and 3.3% with no opioid prescriptions. In the multivariable model, an increased risk of HE was observed with short-term (adjusted hazard ratio, HR 1.44, 95% CI 1.07-1.94) and chronic opioid prescriptions (adjusted HR 1.83, 95% CI 1.07-3.12) compared to no opioid prescriptions. CONCLUSION:In this national cohort of privately insured patients with cirrhosis, opioid prescriptions were associated with the risk of incident HE. Opioid use should be minimised in those with cirrhosis and, when required, limited to short duration.
METHODS:BACKGROUND AND AIMS:Cirrhosis is characterized by extensive fibrosis of the liver and is a major cause of liver-related mortality. Cirrhosis is partially heritable but genetic contributions to cirrhosis have not been systemically explored. Here, we carry out association analyses with cirrhosis in two large biobanks and determine the effects of cirrhosis associated variants on multiple human disease/traits. METHODS:We carried out a genome-wide association analysis of cirrhosis as a diagnosis in UK BioBank (UKBB; 1088 cases vs. 407 873 controls) and then tested top-associating loci for replication with cirrhosis in a hospital-based cohort from the Michigan Genomics Initiative (MGI; 875 cases of cirrhosis vs. 30 346 controls). For replicating variants or variants previously associated with cirrhosis that also affected cirrhosis in UKBB or MGI, we determined single nucleotide polymorphism effects on all other diagnoses in UKBB (PheWAS), common metabolic traits/diseases and serum/plasma metabolites. RESULTS:Unbiased genome-wide association study identified variants in/near PNPLA3 and HFE, and candidate variant analysis identified variants in/near TM6SF2, MBOAT7, SERPINA1, HSD17B13, STAT4 and IFNL4 that reproducibly affected cirrhosis. Most affected liver enzyme concentrations and/or aspartate transaminase-to-platelet ratio index. PheWAS, metabolic trait and serum/plasma metabolite association analyses revealed effects of these variants on lipid, inflammatory and other processes including new effects on many human diseases and traits. CONCLUSIONS:We identified eight loci that reproducibly associate with population-based cirrhosis and define their diverse effects on human diseases and traits.
METHODS:BACKGROUND:Spontaneous bacterial peritonitis (SBP) is a serious complication in patients with liver cirrhosis. In recent years, it has been postulated that the rate of multidrug-resistant organisms (MDROs) is increasing, especially in nosocomial SBP patients. Aim of the present work was to investigate this hypothesis and its possible clinical consequences. MATERIALS AND METHODS:One hundred and three culture-positive patients between 2007 and 2014 were compared with 81 patients between 2015 and 2017, to study the change of microbiological profiles and their clinical consequences. The cirrhosis patients with bacterascites requiring treatment were included as well. RESULTS:The most prevalent Gram-negative bacteria isolated from ascites were Enterobacterales (31.6%) and in Gram-positive pathogens Staphylococci (22.8%). There was a significant increase in MDROs (22.3% ICU 40.7%, P = .048), accompanied by an increased incidence of sepsis (from 21.4% to 37.0%, P = .021), hepatorenal syndrome (from 40.8% to 58.0%, P = .007) and the need of catecholamine therapy (from 21.4% to 38.8%, P = .036). Nosocomial origin correlated with higher MDRO proportion, more complications and lower antimicrobial susceptibility rates in 12 commonly used antibiotics. MDROs were confirmed as an isolated predictor for inpatient mortality and complications in multivariable logistic regression. CONCLUSIONS:The feeling in clinical practice that MDROs have increased in the last 11 years could be confirmed in our study in Munich, Germany. Nosocomial SBP correlated with significantly higher MDRO rates (nearly 50%) and complication rates. In our opinion, an antibiotic combination with comprehensive effect should be taken into account in nosocomial SBP patients in this region.