European Journal of Clinical Investigation最新文献

Background: Antibody-drug conjugates are novel effective therapies for metastatic breast cancer. Nevertheless, their toxicity profile can significantly affect patients' quality of life over time.

Methods: This is a systematic review and meta-analysis of randomized controlled trials of antibody-drug conjugates currently approved for the treatment of metastatic breast cancer [trastuzumab-emtansine (T-DM1), trastuzumab deruxtecan (T-DXd) and sacituzumab-govitecan (SG)] versus standard therapy to evaluate the risk of adverse events, discontinuation rate due to toxicity, impact on quality of life according to EORTC QLQ-C30 scale and subdomains. Relative risks (RR) and hazard ratios (HR) with 95% CIs were calculated using random effects models.

Results: Nine trials with a total of 5753 patients were included. The most common adverse events of any grade for T-DM1 included thrombocytopenia (RR 7.14, 95% CI 4.13-12.36) and increased alanine-transaminase (ALT) (RR 2.04, 95% CI 1.43-2.91), for T-DXd were nausea (RR 2.39, 95% CI 1.90-3.00) and anemia (RR 1.55, 95% CI 1.27-1.90), while for SG were neutropenia (RR 1.30, 95% CI 1.14-1.49), diarrhea (RR 3.62, 95% CI 2.97-4.42) and nausea (RR1.90, 95% CI 1.65-2.19). Severe adverse events such as interstitial lung disease and left ventricular dysfunction were peculiar of T-DXd. Antibody-drug conjugates significantly delayed clinical deterioration of global health status by EORTC QLQ-C30 (HR .71, 95% CI .59-.86), physical, emotional and social functioning, pain and fatigue symptoms.

Conclusions: This meta-analysis offers consolidated data on adverse events associated with antibody-drug conjugates and their effects on patients' quality of life, emphasizing differences based on the specific agent. These findings underscore the critical need for effective strategies to prevent, diagnose and manage these toxicities.

This systematic review and meta-analysis evaluated the impact of glucagon-like peptide-1 receptor agonists (GLP-1RAs) on hepatocellular carcinoma (HCC) and liver decompensation in patients with type 2 diabetes. Analysing over 641,377 patients, GLP-1RA use was associated with a significant 58% reduction in HCC risk, particularly in patients with cirrhotis. While a trend towards reduced liver decompensation risk was observed, it was not statistically significant. These findings suggest a potential role for GLP-1RAs in HCC risk stratification and prevention strategies.

Background: Heart failure (HF) often coexists with cognitive impairment and accelerates cognitive decline. However, the impact of HF medications on cognition has received limited attention. This review evaluates the evidence on the cognitive effects of currently recommended medication classes for HF.

Methods: Systematic review using PubMed and EMBASE following PRISMA guidelines, employing keywords related to HF, cognitive function and guideline-recommended HF medications. Eligible studies were randomized controlled trials (RCT) or cohort studies assessing cognitive function in adult HF patients.

Results: Three cohort studies on ACEi/ARBs (N = 5080; 2 prospective, 1 retrospective) reported no significant impact on cognitive function to higher cognitive scores with ACEi/ARBs. Eight studies on sacubitril/valsartan (ARNI, N = 42,143; all observational studies or post-hoc analyses of RCT) found either no effect on cognitive function or reduced risk of new-onset dementia and improved cognitive outcomes with ARNI. Beta-blockers (N = 40; 1 RCT) lacked significant cognitive effects; empagliflozin (SGLT2i, N = 162; 1 prospective) improved cognitive performance in patients with diabetes and HF with preserved ejection fraction; digoxin (N = 1172; 1 retrospective) was associated with enhanced cognitive function; and statins (N = 112,357; 2 retrospective), which are indicated in HF of ischemic aetiology, were not associated with a significant effect on cognition.

Conclusions: Guideline-recommended HF medication classes appear to have neutral effects on cognitive function, and some may even offer cognitive benefits. However, the limited number and mostly observational nature of studies prevent firm conclusions. Further research is necessary to better understand the cognitive impact of HF medications.

Background: Several studies have investigated the association between Helicobacter pylori colonization and gastrointestinal malignancies. However, inconsistent results have been found, leaving no clear consensus.

Materials and methods: Umbrella review of meta-analyses of observational studies aiming to understand the association between Helicobacter pylori colonization and gastrointestinal cancers in humans. MEDLINE, the Cochrane Library of Systematic Reviews, EMBASE, Scopus and Google Scholar were searched from their inception to January 2025. Quality assessment was performed with the AMSTAR 2 tool. The study was registered on PROSPERO (CRD42024523832).

Results: Of 1320 records, 38 meta-analyses were included, investigating biliary tract, colorectal, oesophageal, gastric, liver and pancreatic cancers. After dealing with primary study overlap and updating meta-analyses with over 160 studies, Helicobacter pylori was positively associated with biliary tract [OR 2.67 (1.57-4.52)], colorectal [OR 1.40 (1.23-1.60)], gastric [OR 2.10 (1.34-3.31)], liver [OR 5.13 (3.14-8.38)] and pancreatic [OR 1.24 (1.04-1.48)] cancers, while oesophageal adenocarcinoma (EAC) was inversely associated with it [OR .58 (.46-.72)]. The cytotoxic-associated gene A (CagA) protein was positively associated with biliary [OR 2.19 (1.07-4.50)], colorectal [OR 2.04 (1.47-2.82)], oesophageal squamous cell carcinoma [OR 1.56 (1.30-1.89)] and gastric cancers [OR 2.53 (1.94-3.30)], and inversely associated with EAC [OR .60 (.44-.81)] and pancreatic [OR .85 (.75-.97)] cancers. Our results sprout from mostly critically low-quality meta-analyses and moderate to high quality primary studies.

Conclusion: Exposure to Helicobacter pylori colonization and its proteins is associated with not only gastric cancer, but also other GI tract cancers. Directionally different results may be seen when specific virulence factors/organ sites are investigated.

Background: Transthyretin amyloid cardiomyopathy (ATTR-CM) commonly leads to heart failure but has traditionally been an exclusion criterion in randomized clinical trials (RCTs) of sodium-glucose cotransporter 2 inhibitors (SGLT2i); therefore, the effects of these drugs in this population remain undocumented. In light of recent studies, this meta-analysis aimed to investigate the effect of SGLT2i on the prognosis of patients with ATTR-CM.

Methods: A comprehensive search of Medline, Scopus, and the Cochrane Library was conducted up to November 17, 2024. Study selection, data extraction and quality assessment were carried out independently by two investigators. Associations of SGLT2i with outcomes were pooled using random-effects meta-analyses.

Results: A total of five studies (9766 participants, 4 propensity score-matched) were included. The use of SGLT2i was associated with significant reductions in all-cause mortality [hazard ratio (HR) .54, 95% confidence interval (CI) .44-.66], cardiovascular mortality (HR .39, 95% CI .23-.65), major adverse cardiovascular events (HR .71, 95% CI .61-.83), and heart failure hospitalizations (HFHs) (HR .63, 95% CI .52-.77) compared to non-use. The odds of cardiac arrhythmias were significantly lower among SGLT2i users compared to non-users [odds ratio (OR) .73, 95% CI .65-.83]. Specifically, SGLT2i use was associated with significant reductions in the odds of atrial fibrillation (AF) (OR .75, 95% CI .62-.91), ventricular tachycardia (OR .72, 95% CI .59-.88), and sudden cardiac arrest (OR .71, 95% CI .50-.99).

Conclusions: The use of SGLT2is may be associated with a more favourable prognosis in patients with ATTR-CM. Adequately powered, long-term RCTs are required to validate the available observational evidence.

From 1999 to 2020, age-adjusted mortality rates (AAMR) for atrial fibrillation-related deaths among U.S. adults (age ≥25) with comorbid diabetes mellitus increased significantly with an annual percent change of 6.5%. The highest mortality rates were observed in males, older adults, non-Hispanic Whites, and residents of urban areas and the West region, underscoring the urgent need for targeted public health strategies.

Background: The Crohn's disease exclusion diet (CDED) has been shown to induce remission in adult Crohn's disease (CD) patients. The aim of the study is to provide additional evidence-based validation.

Methods: We conducted an open-label, randomized trial on adult CD patients with mild-to-moderate symptoms to assess CDED efficacy in inducing symptomatic remission using Mediterranean diet as control. We evaluate demographic data, body mass index (BMI), Harvey-Bradshaw Index (HBI), faecal calprotectin, and serum inflammatory indices at baseline, 12, and 24 weeks. Bioelectrical impedance analysis (BIA) was used to ensure the safety of the CDED group every 12 weeks.

Results: Twenty-four patients were assigned to CDED, and 21 to controls, with no baseline differences among the parameters considered. Five CDED patients dropped out due to intolerance within the first 6 weeks. At 12 weeks, CDED patients showed significantly lower HBI and higher remission rates than controls. By 24 weeks, remission rates increased (70.8% vs. 38.1% at 12 weeks and 79.2% vs. 42.9% at 24 weeks; p = .027 and p < .0001, respectively), with significantly lower fibrinogen levels in the CDED group. The administration of CDED was associated with a significant decrease in BMI (25.8 kg/m²-24.5 kg/m², p = .047), although BIA analysis showed a decrease in fat mass (18.2%-15.5%, p < .0001), while fat-free mass and body cellular mass significantly increased at 12 weeks (p = .001 and p = .042, respectively) and remained stable at 24 weeks.

Conclusions: The CDED was effective in inducing remission among patients with mild-to-moderate CD and appeared to be safe and well-accepted.