Introduction: Non-alcoholic fatty liver disease (NAFLD) has the potential to progress to hepatocellular carcinoma (HCC). However, limited therapies are currently available for the treatment of advanced HCC, and one must strive to search for novel strategies.
Areas covered: We provide insight on current knowledge related to gut microbiota and NAFLD, summarize the sequence linking obesity to HCC and highlight gut dysbiosis in obesity and its consequences on the liver. We detail the impact of the gut microbiota on immune checkpoint inhibitors, and speculate on the role of fecal microbiota transplantation (FMT) in NAFLD and in improving anti-neoplastic immune response.
Expert Opinion: Manipulation of the gut microbiota seems promising in the secondary prevention of NAFLD/NASH and/or in potentiating anti-cancer immune response, notably by a global ‘resetting’ using FMT. However, the composition of a ‘harmful’ gut microbiome in HCC still needs to be characterized, and the impact of FMT on HCC growth needs to be assessed. 相似文献
Objective – To evaluate 12‐week changes from baseline of 2 disease‐specific patient‐reported outcome (PRO) measures in adults with migraine treated with galcanezumab, an investigational humanized antibody binding calcitonin gene‐related peptide (CGRP), or placebo. Background – Preventing headache‐related functional impairment is an important goal of migraine preventive treatment and a measurement target for PROs. Understanding which drugs have the potential to improve patient functioning in addition to preventing migraine headaches is vital to lessening patient burden. Design/Methods – This Phase 2b double‐blind, randomized, placebo‐controlled study enrolled adults with episodic migraine. Galcanezumab (120 mg subcutaneous injection; n = 60) or placebo (n = 127) was administered every 28 days for 12 weeks. Post hoc secondary analyses were conducted for those who completed 12 weeks of treatment on 2 PROs: The Migraine‐Specific Quality of Life Questionnaire (MSQ) v2.1 and the Headache Impact Test? (HIT‐6). Results – Analysis of covariance revealed significant differences in least square mean changes from baseline between galcanezumab and placebo for all MSQ domains including total mean change placebo of 18.63, galcanezumab of 27.36 (95% CI 2.449, 15.008; P‐value of .0067); Role Function‐Restrictive mean change placebo of 22.40, galcanezumab of 31.92 (95% CI 2.636, 16.518; P‐value of .0071); Role Function‐Preventive mean change placebo of 13.43, galcanezumab of 19.76 (95% CI 0.476, 12.185; P‐value of .0342); and Emotional Function mean change placebo of 16.88, galcanezumab of 26.61 (95% CI 2.789, 16.674; P‐value of .0063). At baseline, mean number of migraine headache days (MHDs) did not correlate with MSQ total scores or HIT‐6. At 12 weeks post‐treatment, MHD correlated with MSQ and HIT‐6 scores (all P < .0001). Change in MHD was associated with change in MSQ domains and change in HIT‐6 scores (all P < .0001). Conclusions – In comparison with placebo, treatment with galcanezumab was associated with significant functional improvements as reflected by changes in MSQ scores. Change in MHD was associated with improvements in MSQ and reductions in HIT‐6 scores, indicating the clinical importance of these changes in relation to PROs that measure function. 相似文献
We aimed to determine the impact of transitional care interventions (TCIs) on acute health service use by patients with congestive heart failure in primary care and to identify the most effective TCIs and their optimal duration.
METHODS
We conducted a systematic review and meta-analysis of randomized controlled trials, searching the Medline, PsycInfo, EMBASE, and Cochrane Library databases. We performed a meta-analysis to assess the impact of TCI on all-cause hospital readmissions and emergency department (ED) visits. We developed a taxonomy of TCIs based on intensity and assessed the methodologic quality of the trials. We calculated the relative risk (RR) and a 95% confidence interval for each outcome. We conducted a stratified analysis to identify the most effective TCIs and their optimal duration.
RESULTS
We identified 41 randomized controlled trials. TCIs significantly reduced risks of readmission and ED visits by 8% and 29%, respectively (relative risk = 0.92; 95% CI, 0.87–0.98; P = .006 and relative risk = 0.71; 95% CI, 0.51–0.98; P = .04). High-intensity TCIs (combining home visits with telephone followup, clinic visits, or both) reduced readmission risk regardless of the duration of follow-up. Moderate-intensity TCIs were efficacious if implemented for a longer duration (at least 6 months). In contrast, low-intensity TCIs, entailing only followup in outpatient clinics or telephone follow-up, were not efficacious.
CONCLUSIONS
Clinicians and managers who implement TCIs in primary care can incorporate these results with their own health care context to determine the optimal balance between intensity and duration of TCIs. High-intensity interventions seem to be the best option. Moderate-intensity interventions implemented for 6 months or longer may be another option. 相似文献
BACKGROUNDAtherosclerotic cardiovascular disease (ASCVD) is the leading cause of mortality in patients with nonalcoholic fatty liver disease (NAFLD). Weight loss is a key factor for successful NAFLD and CVD therapy. Ursodeoxycholic acid (UDCA), which is one of the first-line therapeutic agents for treatment of NAFLD, is reported to have a beneficial effect on dyslipidemia and ASCVD risk because of antioxidant properties.AIMTo evaluate the effects of 6 mo of UDCA treatment on hepatic function tests, lipid profile, hepatic steatosis and fibrosis, atherogenesis, and ASCVD risk in men and women with NAFLD, as well as to assess the impact of > 5% weight reduction on these parameters.METHODSAn open-label, multicenter, international noncomparative trial was carried out at primary health care settings and included 174 patients with ultrasound-diagnosed NAFLD who received 15 mg/kg/d UDCA for 6 mo and were prescribed lifestyle modification with diet and exercise. The efficacy criteria were liver enzymes, lipid profile, fatty liver index (FLI), noninvasive liver fibrosis tests (nonalcoholic fatty liver disease fibrosis score and liver fibrosis index), carotid intima-media thickness (CIMT), and ASCVD risk score. To test statistical hypotheses, the Wilcoxon test, paired t-test, Fisher’s exact test, and Pearson''s chi-squared test were used. RESULTSThe alanine aminotransferase (ALT) level changed by -14.1 U/L (-31.0; -5.3) from baseline to 3 mo and by -6.5 U/L (-14.0; 0.1) from 3 to 6 mo. The magnitude of ALT, aspartate transaminase, and glutamyltransferase decrease was greater during the first 3 mo of treatment compared to the subsequent 3 mo (P < 0.001, P < 0.01, P < 0.001, respectively). At 6 mo, in the total sample, we observed a statistically significant decrease in body weight and levels of FLI: 84.9 ± 10.4 vs 72.3 ± 17.6, P < 0.001, total cholesterol: 6.03 ± 1.36 vs 5.76 ± 1.21, Р < 0.001, low-density lipoprotein: 3.86 ± 1.01 vs 3.66 ± 0.91, Р < 0.001, and triglyceride: 3.18 (2.00; 4.29) vs 2.04 (1.40; 3.16), Р < 0.001. No effect on nonalcoholic fatty liver disease fibrosis score or liver fibrosis index was found. The CIMT decreased significantly in the total sample (0.985 ± 0.243 vs 0.968 ± 0.237, P = 0.013), whereas the high-density lipoprotein (Р = 0.036) and 10-year ASCVD risk (Р = 0.003) improved significantly only in women. Fifty-four patients (31%) achieved > 5% weight loss. At the end of the study, the FLI decreased significantly in patients with (88.3 ± 10.2 vs 71.4 ± 19.6, P < 0.001) and without > 5% weight loss (83.5 ± 10.3 vs 72.8 ± 16.7, P < 0.001). The changes in ALT, aspartate transaminase, glutamyltransferase, total cholesterol, and low-density lipoprotein levels were similar between the subgroups.CONCLUSIONUDCA normalizes liver enzymes greatly within the first 3 mo of treatment, improves lipid profile and hepatic steatosis independent of weight loss, and has a positive effect on CIMT in the total sample and 10-year ASCVD risk in women after 6 mo of treatment. 相似文献
OBJECTIVES: This study was designed to determine the likelihood of harm in patients having additional delays before urgent coronary artery bypass graft (UCABG) surgery after percutaneous coronary intervention (PCI). BACKGROUND: Patients who have PCI at hospitals without cardiac surgery have additional delays to surgery when UCABG is indicated. METHODS: Detailed chart review was performed on all patients who had a failed PCI leading to UCABG at a large tertiary care hospital. A prespecified set of criteria (hemodynamic instability, coronary perforation with significant effusion or tamponade, or severe ischemia) was used to identify patients who would have an increased likelihood of harm with additional delays to surgery. RESULTS: From 1996 to 2000, 6,582 PCIs were performed. There were 45 patients (0.7%) identified to have UCABG. The demographic characteristics of the UCABG patients were similar to the rest of the patients in the PCI database, except for significantly more type C lesions (45.3% vs. 25.0%, p < 0.001) and more urgent cases (66.6% vs. 49.8%, p = 0.03) in patients with UCABG. Myocardial infarction occurred in eight patients (17.0%) after UCABG, with a mean peak creatine kinase of 2,445 +/- 1,212 IU/l. Death during the index hospital admission occurred in two patients. Eleven of the 45 patients (24.4%) were identified by the prespecified criteria to be at high likelihood of harm with additional delays to surgery. The absolute risk of harm is approximately one to two patients per 1,000 PCIs. CONCLUSIONS: Approximately one in four patients referred for UCABG would be placed at increased risk of harm if delays to surgery were encountered. 相似文献
OBJECTIVES: This study was designed to compare the three-year survival after percutaneous coronary intervention (PCI) or coronary artery bypass graft surgery (CABG) in physician-directed and patient-choice registries with the Angina With Extremely Serious Operative Mortality Evaluation (AWESOME) randomized trial results. BACKGROUND: The AWESOME multicenter randomized trial and registry compared the long-term survival after PCI and CABG for the treatment of patients with medically refractory myocardial ischemia and at least one additional risk factor for adverse outcome with CABG. The randomized trial demonstrated comparable three-year survival. METHODS: Over a five-year period (1995 to 2000), 2,431 patients with medically refractory myocardial ischemia and at least one of five risk factors (prior heart surgery, myocardial infarction within seven days, left ventricular ejection fraction <0.35, age >70 years, intra-aortic balloon required to stabilize) were identified. By physician consensus, 1,650 patients formed a physician-directed registry assigned to CABG (692), PCI (651) or further medical therapy (307), and 781 were angiographically eligible for random allocation; 454 of these patients constitute the randomized trial, and the remaining 327 constitute a patient choice registry. Survival for CABG and PCI was compared using Kaplan-Meier curves and log-rank tests. RESULTS: The CABG and PCI 36-month survival rates for randomized patients were 79% and 80%, respectively. The CABG and PCI 36-month survival rates were both 76% for the physician-directed subgroup; comparable survival rates for the patient-choice subgroup were 80% and 89%, respectively. None of the global log-rank tests for survival demonstrated significant differences. CONCLUSIONS: Both registries support the randomized trial conclusion: PCI is an alternative to CABG for some medically refractory high-risk patients. 相似文献
OBJECTIVES: The purpose of the study was to evaluate a novel, combined sensor for transcutaneous monitoring of arterial oxygen saturation and carbon dioxide tension. DESIGN: The new monitoring technique was compared to established reference methods. SETTING: ICU and sleep laboratory of a university hospital. PATIENTS: Eighteen critically ill adult patients with acute respiratory failure or heart failure, and 12 patients with sleep apnea (mean [+/- SD] apnea/hypopnea index, 43 +/- 24 events per hour). MEASUREMENTS: Continuous measurements were performed over several hours by the novel heated (temperature, 42 degrees C) earlobe sensor (TOSCA; Linde Medical Sensors; Basel, Switzerland), incorporating electrochemical and optical elements for carbon dioxide measurement (PtcCO2) and pulse oximetry (SpO2), respectively. The data were compared to the results of repeated arterial blood gas analyses in critically ill patients and to simultaneous nocturnal pulse oximetry performed with different devices with earlobe or finger sensors in sleep apnea patients. RESULTS: In critically ill patients, the mean difference and limits of agreement (bias +/- 2 SDs) of transcutaneous PtcCO2 vs arterial PaCO2 were 3 +/- 7 mm Hg; the corresponding values for changes in PtcCO2 vs PaCO2 were 1 +/- 6 mm Hg. The bias +/- 2 SDs for pulse oximetric SpO2 vs arterial oxygen saturation (SaO2) were 1 +/- 4%. In sleep apnea patients, the combined earlobe sensor identified more transient oxygen desaturations, and the rate of change in oxygen saturation during events was greater compared to those with other tested pulse oximeters, indicating a faster response. CONCLUSIONS: Due to its ability to accurately assess both ventilation and oxygenation by a single transcutaneous sensor, the described noninvasive monitoring technique is a valuable tool for respiratory monitoring with potential applications in critical care and sleep medicine. 相似文献
BackgroundThe coronavirus disease 2019 (COVID-19) pandemic has adversely affected diagnosis and treatment of noncommunicable diseases. Its effects on delivery of diagnostic care for cardiovascular disease, which remains the leading cause of death worldwide, have not been quantified.ObjectivesThe study sought to assess COVID-19’s impact on global cardiovascular diagnostic procedural volumes and safety practices.MethodsThe International Atomic Energy Agency conducted a worldwide survey assessing alterations in cardiovascular procedure volumes and safety practices resulting from COVID-19. Noninvasive and invasive cardiac testing volumes were obtained from participating sites for March and April 2020 and compared with those from March 2019. Availability of personal protective equipment and pandemic-related testing practice changes were ascertained.ResultsSurveys were submitted from 909 inpatient and outpatient centers performing cardiac diagnostic procedures, in 108 countries. Procedure volumes decreased 42% from March 2019 to March 2020, and 64% from March 2019 to April 2020. Transthoracic echocardiography decreased by 59%, transesophageal echocardiography 76%, and stress tests 78%, which varied between stress modalities. Coronary angiography (invasive or computed tomography) decreased 55% (p < 0.001 for each procedure). In multivariable regression, significantly greater reduction in procedures occurred for centers in countries with lower gross domestic product. Location in a low-income and lower–middle-income country was associated with an additional 22% reduction in cardiac procedures and less availability of personal protective equipment and telehealth.ConclusionsCOVID-19 was associated with a significant and abrupt reduction in cardiovascular diagnostic testing across the globe, especially affecting the world’s economically challenged. Further study of cardiovascular outcomes and COVID-19–related changes in care delivery is warranted. 相似文献