Diseases (Basel, Switzerland)最新文献

Background: Apolipoprotein E4 (APOE4) represents a major genetic risk factor for Alzheimer's disease. Objectives: We aimed to analyze the relationship between cognitive impairment (CI), unhealthy weight status, and APOE genotypes in individuals of predominantly African descent aged 55 years and more. Genotyping of two single-nucleotide polymorphisms, rs7412 and rs429358, of the APOE gene was performed. Results: Among 310 individuals, the mean age was 75.64 years, the mean BMI was 25.94 kg/m², and the prevalence of CI was 18.1%. Most subjects were ε3/ε3 carriers (49%), while ε2-carriers and ε4-carriers represented 14.5% and 36.5%, respectively. Older age, the presence of undernutrition, and APOE4 carriers were more frequently found in underweight vs. non-underweight individuals and in those with CI vs. those without CI. The adjusted odds ratios for prevalent CI were nearly four times higher for underweight individuals compared to obese individuals. Those carrying two ε4 alleles exhibited three times the odds of CI (OR = 3.31 (95% CI: 1.15-9.91), p = 0.026) compared to those with no ε4 alleles. Conclusions: In this cross-sectional study, being underweight and carrying the ApoE ε4 allele were independently associated with cognitive impairment. These findings suggest that monitoring weight changes and APOE genotypes in older adults may have clinical significance.

Chronic hepatitis C virus (HCV) infection remains a major global health burden, responsible for substantial morbidity and mortality despite the advent of curative antiviral therapy. HCV induces hepatic injury and carcinogenesis through direct viral effects, persistent inflammation, oxidative stress, and metabolic disturbance. The introduction of direct-acting antivirals (DAAs) has revolutionized therapy, achieving sustained virologic response rates exceeding 95% and transforming HCV from a chronic, progressive disease into a curable infection. Nevertheless, viral eradication does not fully normalize hepatic or systemic risk. Patients with advanced fibrosis or cirrhosis continue to face an elevated incidence of hepatocellular carcinoma (HCC) and other complications, reinforcing the need for long-term monitoring. This review summarizes current knowledge of the molecular mechanisms underlying HCV-mediated carcinogenesis, the partial restoration of hepatic homeostasis following DAA-induced cure, and the clinical implications for surveillance and management in the post-HCV era. By integrating insights from molecular virology, immunopathogenesis, and clinical hepatology, the review highlights how persistent epigenetic and inflammatory footprints may sustain oncogenic potential even after viral clearance. A comprehensive understanding of these processes is essential for optimizing HCC prevention strategies, guiding surveillance policies, and advancing future therapeutic innovations aimed at complete hepatic recovery.

Background: Colorectal cancer (CRC) incidence and mortality have declined in the United States over the past two decades, yet disparities persist by age, sex, race/ethnicity, and geography. To characterize population-level survival signals, we examined trends in age-adjusted incidence rates (AAIR), mortality rates (AAMR), and the mortality-to-incidence ratio (AAMIR) from 1999 to 2021, stratified by key subgroups. Methods: This retrospective analysis utilized de-identified data from the CDC WONDER United States Cancer Statistics database, encompassing incident CRC cases (SEER codes 21041-21052) and deaths (ICD-10 codes C18-C20) in adults aged 20 years and older. Age-adjusted rates (per 100,000, 2000 U.S. standard population) and AAMIR were calculated using Stata 17.0. Joinpoint regression identified trends (annual or average annual percent change [APC/AAPC], p < 0.05). Results: Among 3,489,881 cases and 1,225,986 deaths, AAIR decreased from 78.24 (1999) to 50.79 (2021; AAPC: -2.20%, 95% CI: -2.52 to -1.89), AAMR decreased from 29.34 to 17.92 (AAPC: -2.33%, -2.46 to -2.20), and AAMIR from 0.375 to 0.353 (AAPC: -0.08%, -0.47 to 0.30; p = 0.669). Women showed a significant AAMIR decline (AAPC: -0.29%), unlike men (AAPC: 0.07%). Young adults (20-39 years) had rising AAIR (AAPC: 2.42%) and AAMR (0.87%) but improving AAMIR (AAPC: -1.71%). Non-Hispanic Black individuals had the highest AAMIR (0.400 in 2021; AAPC: -0.54%). The Northeast had the most favorable AAMIR trend (AAPC: -0.40%), while the Midwest, South, and West were stable. States like New Jersey and Massachusetts achieved low AAMIR (0.292 and 0.304 in 2021), contrasting with Nebraska and Arizona (0.402 in both). Conclusions: Although colorectal cancer incidence and mortality have declined substantially in the United States from 1999 to 2021, the mortality-to-incidence ratio improved only marginally and remained markedly uneven across subgroups. Targeted interventions-enhancing screening and treatment access for men, racial/ethnic minorities, younger adults, and high-burden regions and states-can promote equitable outcomes.

Background/Objectives: COVID-19 infection is a respiratory illness that affects multiple body systems, including the musculoskeletal system. In August 2024, Colombia reported 6 million infections and a 2.2% mortality rate related to COVID-19. Post-COVID-19 syndrome (PCS) is a chronic condition occurring after the acute infection, typically characterized by fatigue, weakness, pain, and sarcopenia, impacting the patient's quality of life (QoL). This systematic review aimed to identify musculoskeletal sequelae, including peripheral muscle strength, fatigue, and QoL, in patients with PCS. Methods: We searched the PubMed, Scopus, and Web of Science databases for cross-sectional, case-control, and cohort studies focusing on musculoskeletal sequelae in patients with COVID-19 infection published between 2020 and 2025. Study quality and risk of bias were assessed using the MINORS and the ROBINS-E scales, respectively. Results: Thirteen studies (n = 5657 patients) met the eligibility criteria. Seventy-six percent of studies indicated muscle weakness as the most common sequela, primarily in older adults and individuals with comorbidities (obesity, diabetes, and chronic obstructive pulmonary disease). General fatigue (reported in 76% of the studies) significantly influenced patients' daily lives, whereas 90% of patients reported some level of deterioration in their QoL, primarily regarding mental health, bodily pain, and physical performance. Conclusions: Patients with PCS who required mechanical ventilation showed reduced muscle strength and poor physical performance, especially older adults. Inactive individuals had worse musculoskeletal sequelae, while physical activity was associated with better strength levels. Although QoL improved after 12 months, the combination of aerobic exercise with adequate nutrition is essential to promote muscle recovery, reduce fatigue, and improve overall functional capacity in post-COVID-19 patients.

Background: Obesity is a metabolic condition that may impair insulin sensitivity and disrupt glucose homeostasis. Since insulin and glucose affect insulin-like growth factor-1 (IGF-1), disruptions in this axis may elevate the risk of chronic diseases. Intermittent fasting (IF) modulates metabolic parameters, but the impacts on glucose regulation and IGF-1 remain underexplored. This study aimed to assess the short-term effects of two IF types, time-restricted feeding (TRF) and alternate-day modified fasting (ADMF), on fasting blood glucose (FBG) and IGF-1 in obese young women. Methods: A quasi-experimental pretest-posttest control group design was conducted over 20 days. The 31 subjects were allocated into ADMF (n = 10), TRF (n = 11), and Control (n = 10). After excluding dropouts and outliers, the final sample consisted of 22 subjects (ADMF = 7, TRF = 8, Control = 7). FBG and IGF-1 serum were measured pre- and post-intervention. Results: The FBG post-intervention significantly increased in TRF (p = 0.001) and ADMF (p = 0.036) groups, but not in Controls. Only the TRF group showed a significant reduction in IGF-1 levels (p < 0.001). Nevertheless, the ADMF group exhibited substantial decreases in body weight (p = 0.047) and visceral fat (p = 0.017). Conclusions: A 20-day IF in obese young women induced distinct metabolic effects: TRF lowered IGF-1, ADMF reduced adiposity, and both regimens increased FBG. These findings suggest that early changes in glucose regulation are highly dependent on the specific dietary regimen used. Specifically, TRF predominantly influences endocrine regulation (IGF-1 axis), while ADMF favours adiposity reduction. The concurrent rise in FBG may reflect a transient shift in glucose homeostasis during the early stages of fasting.

Background: Palliative care has emerged as a key component in the management of chronic heart failure, addressing persistent physical and psychosocial symptoms that often remain insufficiently controlled by conventional cardiology. This systematic review aimed to evaluate the impact of palliative care interventions on symptom burden, quality of life (QoL) and decision-making processes in adults with chronic heart failure.

Methods: A systematic search of PubMed, Scopus and Web of Science identified studies published between January 2005 and February 2025. Eligible designs included randomized controlled trials, observational cohorts and qualitative studies. The review followed PRISMA 2020 guidelines. Methodological quality was assessed using the Cochrane Risk of Bias 2.0 (RoB 2.0), Risk of Bias in Non-Randomized Studies of Interventions (ROBINS-I) and Joanna Briggs Institute (JBI) appraisal tools. Due to heterogeneity in study designs and outcomes, a narrative synthesis was conducted.

Results: Nineteen studies met the inclusion criteria. Palliative care interventions consistently reduced dyspnea, fatigue, anxiety and depression and were associated with improved functional status and QoL. Integrated palliative-cardiology programs were linked to fewer hospital readmissions, shorter hospital stays and increased documentation of advance care planning. However, methodological variability, small sample sizes and non-standardized outcome measures limited comparability across studies.

Conclusions: The evidence supports the early incorporation of palliative care into routine management of chronic heart failure. Early, multidisciplinary and patient-centered approaches enhance clinical and psychosocial outcomes while improving healthcare efficiency and ensuring that care aligns with patients' goals, values and quality-of-life priorities.

Background: Immunological monitoring in multiple sclerosis (MS) patients treated with disease-modifying drugs may help predict infectious complications and guide treatment. The main objective of this study was to evaluate whether anti-CD20 treatments in MS patients induce immunodeficiency and whether certain immunological parameters can predict the risk of infection and response to treatment.

Methods: This retrospective, observational, single-centre study included MS patients who started treatment with ocrelizumab or rituximab and received follow-up in the Neuroimmunology Unit of our centre between January 2017 and January 2023. The study was conducted in collaboration with the Immunology Department of this hospital.

Results: Fifty-five patients were included, with a mean age of 47 years and a follow-up period of 24 months. Analyses of lymphocyte subpopulations (T, B, NK) and immunoglobulin levels (IgG, IgA, IgM) were performed before treatment and at 6-, 12- and 24-month follow-ups. In addition, we carried out an exhaustive study of B cells in the baseline analysis. Sixty-four percent of patients presented infections, mostly due to COVID-19. Three patients developed cryptogenic organising pneumonia. IgG hypogammaglobulinemia was the main risk factor for developing infections. Patients with infections had fewer mature memory B cells and a lower percentage of NK cells. Furthermore, a lower proportion of naïve and mature memory B cells was associated with inflammatory activity and disease progression, respectively. The absence of CD20 depletion during follow-up was associated with clinical worsening.

Conclusions: Baseline immunophenotype and immunological monitoring can help predict the risk of infections and the efficacy of anti-CD20 therapy in MS patients.

Background: Central line-associated bloodstream infections (CLABSIs) in neonatal intensive care units (NICUs) pose a significant risk, especially for very low birth weight infants due to their immature immune systems and the need for invasive procedures. The implementation of evidence-based bundles, as recommended by international guidelines, has proven effective in significantly reducing CLABSI rates, improving clinical outcomes, and lowering hospital costs. However, evidence from long-term, real-world quality-improvement programs in European NICUs-especially those using repeated PDSA cycles and detailed monitoring across multiple periods-remains limited. Methods: This quality improvement prospective study, conducted in the NICU of "V. Buzzi" Children's Hospital, aimed to reduce high CLABSI rates using a plan-do-study-act (PDSA) framework. A multidisciplinary team developed and implemented a new evidence-based central line bundle in 2021, focusing on standardized practices, enhanced training, and monitoring. The study analyzed 594 CVCs placed in 348 neonates across a total 4-years period (P1-P12). Results: Implementation of a central line bundle significantly reduced CLABSI rates from 29.1 to 2.2 per 1000 CVC days (p-value 0.002), with notable variations during intermediate periods. Birth weight and study period progression were the only variables significantly associated with CLABSI reduction. Conclusions: Infection rates dropped significantly post-intervention, achieving zero in one of the latest periods: continuous monitoring, staff training, and targeted interventions were pivotal. Future efforts will focus on refining practices, increasing tunneled centrally inserted central catheter (CICC) use, and sustaining prevention measures.

Background: Melioidosis, caused by Burkholderia pseudomallei, remains a major cause of sepsis-related mortality in tropical regions. Despite effective antimicrobial therapy, deaths frequently result from dysregulated host inflammation rather than uncontrolled bacterial replication. Interleukin-6 (IL-6), a key mediator of systemic inflammation, has been proposed as a prognostic biomarker in sepsis, but its predictive value in melioidosis has not been systematically evaluated. Methods: A systematic review and meta-analysis were performed following PRISMA 2020 guidelines (PROSPERO CRD420251152797). MEDLINE, Embase, and Scopus were searched from inception to 15 March 2025. Eligible studies included patients with culture-confirmed melioidosis reporting circulating IL-6 concentrations stratified by survival outcome. Standardized mean differences (SMDs) with 95% confidence intervals (CIs) were pooled using random effects models. Heterogeneity and robustness were examined through leave-one-out and sensitivity analyses. Publication bias assessment was not performed due to insufficient study numbers (n = 4). Results: Eight studies were included qualitative systematic review, and four studies comprising 411 patients were eligible for quantitative meta-analysis. Pooled analysis demonstrated significantly higher IL-6 levels among non-survivors compared with survivors (SMD = 0.80, 95% CI 0.02-1.57; I² = 86.3%). Leave-one-out diagnostics indicated no single study unduly influenced the pooled effect. Sensitivity analysis excluding the largest dataset reduced heterogeneity to 34.5% and yielded an SMD of 0.51 (95% CI -0.28-1.30), maintaining the same direction of association. Conclusions: Circulating IL-6 levels are elevated in fatal melioidosis and may serve as a promising prognostic biomarker for mortality. Although interstudy heterogeneity was substantial, the association remained consistent in direction across populations and analytical methods despite the limited number of eligible studies. These findings support further prospective validation of IL-6 in clinical risk stratification and host response-guided management of severe melioidosis, though larger multicenter studies are needed to confirm these preliminary findings.