Search Results (2,070)

Background/Objectives: Naringin, a major flavonoid found in citrus fruits, has garnered significant attention over the past two decades for its potential cardiovascular benefits. This systematic review evaluates the effects of naringin on endothelial function and myocardial performance, with particular emphasis on ischemia-reperfusion (I/R) injury, based on the literature published from January 2000 to June 2025. Methods: The review was conducted in accordance with PRISMA 2020 guidelines. A comprehensive search of PubMed, Scopus, EMBASE, and Web of Science databases was performed using key terms including “naringin”, “cardiovascular”, “endothelial function”, “atherosclerosis”, and “ischemia-reperfusion.” A total of 62 studies were included and categorized into three domains: cellular models, animal studies, and human trials. Risk of bias assessments were conducted for each study type using appropriate tools. Results: Naringin consistently exhibited antioxidant, anti-inflammatory, and vasoprotective effects across all study types. Mechanistic studies highlighted the modulation of key signaling pathways, including PI3K/Akt, NF-κB, Nrf2, the renin-angiotensin system (RAS), and enhancement of KATP channel expression, as well as its ability to inhibit apoptosis, autophagy, and ferroptosis. In animal models, naringin improved endothelium-dependent vasorelaxation, reduced infarct size, and preserved myocardial function. Although limited, human trials reported beneficial effects on lipid profiles, arterial stiffness, and adiponectin levels. Conclusions: Naringin demonstrates strong potential as a dietary adjunct for cardiovascular protection, especially in the context of ischemic injury and vascular dysfunction. Further well-designed clinical trials are needed to define optimal dosing strategies and improve its bioavailability in humans. Full article

Background: Perioperative factors significantly impact oncologic outcomes after radical cystectomy (RC) for bladder cancer. This study aimed to identify key perioperative predictors for overall (OS) and progression-free survival (PFS) and to develop a prognostic nomogram for the identification of high-risk patients adapted to the clinical routines and standard of care of our country. Methods: We retrospectively analyzed 121 patients undergoing RC (2014–2024). Data on patient demographics, comorbidities, tumor pathology, neoadjuvant treatments, extensive intraoperative factors, and postoperative events were assessed using COX models. A prognostic nomogram for 3-year OS was constructed. Results: Median follow-up was 44.33 months. Significant predictors for worse OS included lymphovascular invasion (LVI) (HR 2.22), higher T stage (HR 8.75), N+ status (HR 1.10), and intraoperative complications (HR 3.04). Similar predictors were noted for PFS. The developed nomogram incorporated T-, N-stages, sex, grade, intraoperative complications and early (12 months) recurrence, and was able to significantly identify patients with a higher mortality risk (p < 0.001) with a C-index of 0.74. Conclusions: Our nomogram for mortality prediction of BC patients offers a promising tool for individualized risk stratification. Further studies are required for its external validation. Full article

Background/Objectives: Physical training and Pulmonary Rehabilitation in Patients with Cystic Fibrosis: A Systematic Review and Meta-Analysis of Clinical Trials. Pulmonary rehabilitation and physical training are essential components of the comprehensive management of patients with cystic fibrosis. Despite documented benefits for some clinical outcomes, uncertainty exists regarding their overall effects. Therefore, the objective of the present meta-analysis is to determine the effectiveness of physical training and pulmonary rehabilitation in patients with CF. Methods: This systematic review and meta-analysis of randomized controlled trials published between 1990 and 2025 was conducted using the PubMed, Cochrane Clinical Trial, SCOPUS, Science Direct, Web of Science, Scielo, and LILAC databases. The risk of bias was evaluated using the RoB 2 tool, the quality of the evidence with the Jadad scale, and the certainty of the evidence for each outcome was assessed according to GRADE guidelines. This meta-analysis was developed using the statistical packages RevMan 5.4^® and Jamovi 2.3.28^®. Results: Twenty-three studies with a total of 800 patients with CF were included. This meta-analysis showed that pulmonary rehabilitation and physical training did not affect pulmonary function, as observed in FEV1 (SMD: 0.05; 95% CI: −0.09 to 0.20; p = 0.46) and FVC (SMD: 0.11; 95% CI: −0.04 to 0.27; p = 0.14). However, it has a discrete impact on exercise capacity, producing an increase in VO₂ max (MD: 2.74; 95% CI: 0.43 to 5.04; p = 0.02). Subgroup analyses did not yield relevant findings, and sensitivity analyses did not produce modifications in the direction or magnitude of the effect. Conclusions: The intervention evaluated in this meta-analysis does not have effects on pulmonary function but may influence exercise capacity, particularly VO₂ max. It is recommended to interpret the findings with caution due to the limited certainty of the available evidence. Full article

Background: The widespread use of cardiac magnetic resonance imaging (MRI) in clinical practice has enabled the identification of numerous patients with evident damage from previous myocarditis, whether known or unknown. For years, myocardial fibrosis has been a topic of interest due to its established correlation with arrhythmic events in various clinical settings, including ischemic heart disease, dilated cardiomyopathy, and hypertrophic cardiomyopathy. MIBG scintigraphy is a method widely used in patients who are candidates for defibrillator implantation or have experienced heart failure. This examination evaluates the sympathetic innervation of the myocardium. Objective: To assess the real arrhythmogenic risk of non-ischemic scars identified in symptomatic or asymptomatic patients through the use of MIBG. Methods: Patients were retrospectively selected based on the presence of non-ischemic myocardial fibrosis detected by cardiac MRI, consistent with a myocarditis outcome (even in the absence of a clear history of myocarditis). These patients underwent myocardial scintigraphy with MIBG using a tomographic technique. Results: A total of 50 patients (41 males, mean age 51 ± 16 years) who underwent MRI from 2019 to June 2024 were selected. The primary indication for MRI was ventricular ectopic extrasystoles detected on Holter ECG (n = 12, 54%), while five patients underwent MRI following a known acute infectious event (23%, including three cases of COVID-19 infection). All symptomatic patients presented with chest pain in the acute phase, accompanied by elevated hsTNI levels (mean value: 437 pg/mL). The MRI findings showed normal ventricular volumes (LV: 80 mL/m², RV: 81 mL/m²) and normal ejection fractions (56% and 53%, respectively). The mean native T1 mapping value was 1013 ms (normal range: 950–1050). T2 mapping values were altered in the 5 patients who underwent MRI during the acute phase (mean value: 57 ms), without segmentation. Additionally, three patients had non-tamponade pericardial effusion. All patients exhibited LGE (nine subepicardial, seven midwall, six patchy). All patients underwent myocardial scintigraphy with MIBG at least 6 months after the acute event, with only one case yielding a positive result. This patient, a 57-year-old male, had the most severe clinical presentation, including more than 65,000 premature ventricular beats (PVBs) and multiple episodes of paroxysmal supraventricular tachycardia (PSVT) recorded on Holter ECG. MRI findings showed severe left ventricular dysfunction, a slightly dilated LV, and midwall LGE at the septum, coinciding with hypokinetic areas. Conclusions: MIBG scintigraphy could be a useful tool in assessing arrhythmic risk in patients with previous myocarditis. It could help reduce the clinical burden of incidental findings of non-ischemic LGE, which does not appear to be independently associated with an increased risk profile. Full article

Background/Objectives: Tinnitus has been increasingly recognized not only as an auditory disturbance but also as a condition that is potentially linked to cognitive decline, particularly in older adults. However, the relationship between tinnitus characteristics and cognitive impairment remains underexplored in clinical settings. This study aimed to (1) evaluate the association between chronic tinnitus and cognitive function in adults aged 60 years and above using standardized tools, and (2) determine whether tinnitus severity and duration are associated with increased risk of cognitive impairment. Methods: A cross-sectional study was conducted among 240 older adults, divided into tinnitus (n = 120) and non-tinnitus (n = 120) groups. Cognitive function was assessed using the Mini-Cog (0–5) and SPMSQ (0–10) tools. Tinnitus severity and duration were evaluated using the Tinnitus Handicap Inventory (THI), Visual Analogue Scale (VAS), and duration categories. Results: Participants with tinnitus were significantly older and had higher rates of hearing loss (58.33% vs. 33.33%, p = 0.001), depression (37.50% vs. 18.33%, p = 0.002), and poor sleep quality (51.67% vs. 31.67%, p = 0.003). Mini-Cog and SPMSQ scores were significantly lower in the tinnitus group (2.87 ± 1.14 vs. 3.52 ± 1.06; 6.95 ± 1.42 vs. 8.02 ± 1.18; both p < 0.001). Tinnitus presence, longer duration, and higher severity were independently associated with cognitive impairment. Each 10-point increase in THI score increased the odds of impairment by 45% (OR = 1.45, p < 0.001). Conclusions: Tinnitus burden, particularly when severe and prolonged, is significantly associated with cognitive impairment in older adults. These findings highlight the need for cognitive screening and integrated management in this population. Full article

This study aimed to describe the risk factors for locomotive syndrome (LS) in Brazilian oldest old individuals. Study subjects were older adults aged ≥80 years who were cognitively healthy, independent for activities of daily living and had been followed since 2011 by a Brazilian cohort study entitled the Longevos Project. A nested case–control study evaluating demographic and clinical characteristics was conducted. Physical tests including the 5 times sit-to-stand, hand-grip strength, 4-m gait speed and two-step test were performed. The World Health Organization Quality of Life Questionnaire short form (WHOQOL-BREF) and Numerical Rating Scale plus Verbal Rating Scale were applied to assess quality of life (QOL) and chronic pain (CP), respectively. LS was diagnosed using the Brazilian version of the 25-question Geriatric Locomotive Function Scale (GLFS-25-p), and sarcopenia by the SARC-F screening tool. The study sample included 52 participants, had a mean age of 89.3 years (±3.9 years) and was predominantly female (76.9%). Of this sample, 24 were diagnosed with LS and 28 were not. The prevalence of osteoporosis (20%), osteoarthritis (22%), depression (13%) and use of a walking device (14%) was higher in the LS group. Participants with LS had worse performance in physical tests. A multivariate logistic regression analysis identified the main risk factors for LS as osteoporosis (OR 10.80, 95%CI 1.08–108.48) and presence of moderate-to-severe chronic musculoskeletal pain (OR 8.92, 95%CI 1.25–63.89). Full article

Background: Myasthenia gravis (MG), a chronic autoimmune disorder with variable disease trajectories, presents considerable challenges for clinical stratification and acute care management. This systematic review evaluated machine learning models developed for prognostic assessment in patients with MG. Methods: Following PRISMA guidelines, we systematically searched PubMed, Embase, and Scopus for relevant articles published from January 2010 to May 2025. Studies using machine learning techniques to predict MG-related outcomes based on structured or semi-structured clinical variables were included. We extracted data on model targets, algorithmic strategies, input features, validation design, performance metrics, and interpretability methods. The risk of bias was assessed using the Prediction Model Risk of Bias Assessment Tool. Results: Eleven studies were included, targeting ICU admission (n = 2), myasthenic crisis (n = 1), treatment response (n = 2), prolonged mechanical ventilation (n = 1), hospitalization duration (n = 1), symptom subtype clustering (n = 1), and artificial intelligence (AI)-assisted examination scoring (n = 3). Commonly used algorithms included extreme gradient boosting, random forests, decision trees, multivariate adaptive regression splines, and logistic regression. Reported AUC values ranged from 0.765 to 0.944. Only two studies employed external validation using independent cohorts; others relied on internal cross-validation or repeated holdout. Of the seven prognostic modeling studies, four were rated as having high risk of bias, primarily due to participant selection, predictor handling, and analytical design issues. The remaining four studies focused on unsupervised symptom clustering or AI-assisted examination scoring without predictive modeling components. Conclusions: Despite promising performance metrics, constraints in generalizability, validation rigor, and measurement consistency limited their clinical application. Future research should prioritize prospective multicenter studies, dynamic data sharing strategies, standardized outcome definitions, and real-time clinical workflow integration to advance machine learning-based prognostic tools for MG and support improved patient care in acute settings. Full article

Mucositis involving the gastrointestinal, vaginal, and nasal mucosa is one of the primary dose-limiting toxicities of hematopoietic stem cell transplantation (HSCT) and its conditioning regimen. The oropharyngeal mucosa is commonly affected, which can be detrimental to patient health and quality of life. Despite its significant prevalence and deleterious effects, we have an inadequate understanding of the risk factors and outcomes associated with oral mucositis (OM). We performed a literature search through PubMed and EBSCO (inception to 31 March 2024) following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Data was extracted from eligible studies using a pre-specified data extraction form. Quality of the data was assessed using the Newcastle-Ottawa Scale for non-randomized, observational studies and the Cochrane Collaboration Tool for randomized controlled trials. Our initial search identified 1677 articles, 34 of which were included in our study. Of those 34, 30 were included in the qualitative assessment of clinical risk factors in the development of OM, and 4 were included in the meta-analysis assessing the relationship between OM and infectious complications following HSCT. Across both HSCT modalities and cancer cohorts, female sex and high-intensity conditioning were common risk factors in the development of OM. When stratified by allogeneic and autologous HSCT, methotrexate, younger age, and longer duration of neutropenia were associated with increased OM risk in allogeneic HSCT recipients, while renal dysfunction, HSV-1 reactivation, and longer neutrophil engraftment were associated with increased OM risk in autologous HSCT recipients. Longer neutrophil engraftment was a common risk factor across different cancer cohorts; however, renal dysfunction was a distinct risk factor for OM in multiple myeloma patients. Additionally, our meta-analysis revealed that patients with OM have an increased risk of developing infectious complications following HSCT compared to those without OM, with an odds ratio of 3.84 (95% CI: 2.51–5.86). The development of OM is related to various risk factors, and individuals with OM are at greater risk of infectious complications. Knowledge of these risk factors and outcomes will help clinicians identify high-risk individuals, prevent OM, and protect an immunocompromised population from subsequent life-threatening complications. Full article

Background: Early detection of patients at high risk for recurrence or local tumor progression (LTP) following thermal ablation of hepatocellular carcinoma (HCC) is essential for treatment selection and individualized follow-up. This systematic review aims to assess and compare the performance of prognostic models predicting recurrence or LTP in patients with HCC treated with thermal ablation. Methods: PubMed, Web of Science, Cochrane, and Embase were searched for studies developing models to predict recurrence after thermal ablation in treatment-naïve HCC patients, using imaging and clinical data with reported test set performance. Risk of bias and applicability were assessed by the Prediction model Risk of Bias Assessment Tool. Data on model performance, feature extraction and modeling technique was collected. Results: In total, 16 studies comprising 39 prognostic models were included, all developed using retrospective data from China or Korea. Outcomes included recurrence-free survival, (intrahepatic) early recurrence, LTP, late recurrence and aggressive intrasegmental recurrence. Predictive parameters varied across models addressing identical outcomes. Outcome definitions also differed. Nine models were externally validated. Most studies had a high risk of bias due to methodological limitations. Conclusions: Variability in model development methodology and type of predictors was found. Models that integrated multiple types of predictors consistently outperformed those relying on one type. To advance predictive tools toward clinical implementation, future research should prioritize standardized outcome definitions, external testing, and transparent reporting. Until these challenges are addressed, current evaluated models should be regarded as promising but preliminary tools. Full article

Background: The treatment of burns is a socio-economic challenge for both patients and the National Health Service. Early debridement and skin graft reduces the risk of local and systemic complications. However, when skin autografting is unfeasible or contraindicated, alternative options are required. Recent research has introduced new potential tools: fish skin grafts (FSGs). This systematic review focuses on FSGs with the aim of improving the management of burn patients. Methods: A systematic search on articles concerning FSG for the treatment of burns was performed by searching PubMed, Web of Science and Embase according to the PRISMA statement. Clinical trials, retrospective studies, case series and case reports were included. Results: A total of 36 studies were identified through the search strategy and imported for screening. After duplicate removal, 26 studies were considered. Based on predetermined criteria, 20 full texts were assessed for eligibility, leaving 18 articles to be included in the systematic review. Conclusions: By virtue of the safety and effectiveness of FSGs, including low risk of zoonosis transmission and valuable outcomes even in austere environments, FSGs could represent a new alternative for the treatment of burns. Full article

Background: Coronary artery calcium (CAC) scores are a widely used surrogate marker for atherosclerotic burden, but they do not fully reflect plaque vulnerability or coronary inflammation. This study aimed to evaluate the relationship between CACs, coronary plaque characteristics, and perivascular inflammatory activity using advanced CCTA and CaRi-Heart^® analysis. Methods: A total of 250 patients with no prior cardiovascular disease were retrospectively evaluated and stratified by CACs into three groups: 0 (n = 28), 1–100 (n = 121), and >100 (n = 101). Coronary plaque morphology, high-risk plaque (HRP) features, CAD-RADS scores, and AI-derived fat attenuation index (FAI) centiles were assessed. Results: Significant differences across CAC categories were observed for several key parameters. The number of diseased coronary segments increased markedly (from 1.39 ± 1.10 vs. 2.97 ± 1.57 vs. 3.94 ± 2.10; p < 0.0001, one-way ANOVA). A similar upward trend was seen for segment involvement scores, HRP prevalence, and the proportions of mixed and calcified plaque components. Regression analysis demonstrated that CACs correlated significantly with segment burden (r² = 0.2520), CAD-RADS (r² = 0.1352), and the FAI score centile (r² = 0.0568). Conclusions: This study highlights the limitations of CACs as a standalone risk stratification tool. Vulnerable and inflamed plaques may already be present in patients with low or zero CACs. Integrating CCTA with perivascular FAI mapping enables earlier detection of biologically active atherosclerosis and supports more precise clinical decision-making. Full article

Background/Objectives: Moderate or severe asthma exacerbations may require pharmacological interventions in addition to standard treatment. In this context, magnesium sulfate has been proposed as a second-line therapeutic option, owing to its physiological effects on bronchial smooth muscle. Therefore, the objective of this meta-analysis is to determine the effectiveness of intravenous or nebulized magnesium sulfate in patients with a moderate-to-severe asthmatic crisis. Methods: This systematic review and meta-analysis included randomized controlled trials published between 1990 and 2024, using the PubMed, Scopus, Science Direct, Web of Science, LILACS, Cochrane Library, Springer, and Scielo databases. The risk of bias was assessed using the RoB 2 tool, the quality of evidence with the Jadad scale, and the certainty of the evidence per outcome was evaluated following the GRADE guidelines. The meta-analysis was developed using the statistical software Jamovi 2.3.28^® and RevMan 5.4^®. Results: Fourteen studies with a total of 2242 patients with a moderate-to-severe asthmatic crisis were included. Of these, ten studies evaluated the severity score, eight evaluated hospitalization, five evaluated the length of the hospital stay, and three evaluated intensive care unit admission. The meta-analysis demonstrates that the use of magnesium sulfate is associated with a statistically significant reduction in the risk of hospitalization (RR: 0.79, 95% CI: from 0.67 to 0.94, p = 0.02). However, no effects were observed on the severity score (SMD: −0.37, 95% CI: from −0.92 to 0.17, p = 0.16), the length of the hospital stay (SMD: −0.75, 95% CI: from −1.90 to 0.40, p = 0.14), or admission to intensive care units (RR: 0.62, 95% CI: from 0.28 to 1.36, p = 0.23). Subgroup and sensitivity analyses did not yield significant findings or produce any modification of the effect. Conclusions: Magnesium sulfate reduces hospitalizations in moderate-to-severe pediatric asthma, although it does not improve other relevant clinical outcomes. Full article

Chronological age is an imprecise proxy for reproductive capacity, necessitating biomarkers that reflect the underlying pathophysiology of the ovary. Fibrotic remodeling of the ovarian stroma is a key hallmark of biological ovarian aging, yet it cannot be assessed by current clinical tools. This study aimed to identify and validate a novel serum biomarker for fibrotic ovarian aging by applying supervised machine learning (ML) to human ovarian transcriptomic data. Transcriptomic data from the Genotype-Tissue Expression (GTEx) database were analyzed using ML algorithms to identify candidate genes predictive of ovarian aging, and finally, fibroblast activation protein (FAP) and collectin-11 (COLEC11) were selected for clinical validation. In a cross-sectional study, serum levels of FAP and COLEC11, along with key hormonal indices, were measured in two nested patient cohorts, and their associations with ovarian reserve and clinical parameters were analyzed. Serum FAP levels did not correlate with age but showed a strong inverse correlation with anti-Müllerian hormone (AMH) (r = −0.61, p = 0.001), a finding accentuated in women with decreased ovarian reserve (DOR). While COLEC11 correlated with age, it failed to differentiate DOR status. FAP levels were independent of central hormonal regulation, consistent with preclinical fibrotic models. Circulating FAP reflects age-independent, fibrotic ovarian aging, offering stromal-specific information not captured by conventional hormonal markers. This study provides the first clinical validation of FAP as a biomarker for ovarian stromal aging, holding potential for improved reproductive risk assessment. Full article

Background: Gastrointestinal immune-related adverse events (GI-irAEs) are recognized complications of immune checkpoint inhibitors (ICIs), but their prognostic relevance and associated risk factors remain unclear. This study aimed to assess whether baseline nutritional status, measured using the prognostic nutritional index (PNI), modifies the prognostic impact of GI-irAEs, and to identify clinical factors associated with their occurrence. Methods: We retrospectively analyzed 1104 cancer patients treated with ICIs at a single institution. GI-irAEs were defined as gastrointestinal symptoms requiring clinical intervention. Patients were stratified by irAE type and PNI (≥40 vs. <40), and differences in survival and treatment response were evaluated. Potential risk factors for developing GI-irAEs were also examined. Results: GI-irAEs occurred in 2.7% of patients and were associated with prolonged overall survival (median: 28.7 vs. 14.0 months) among those with PNI ≥ 40. This survival advantage was not observed in patients with PNI < 40. The PNI-dependent prognostic pattern was specific to GI-irAEs and not observed for non-GI irAEs. Similar trends were confirmed in 4- and 8-week landmark analyses. Differences in objective response rate and disease control rate by PNI status were most pronounced in patients with GI-irAEs. The use of anti-CTLA-4 antibodies was significantly associated with GI-irAE development (odds ratio 4.24; 95% confidence interval 1.73–10.39). Conclusions: GI-irAEs appear to confer a survival benefit primarily in patients with preserved nutritional status. PNI may serve as a useful tool to contextualize the clinical relevance of GI-irAEs and help identify patients most likely to benefit from immune activation during ICI therapy. Full article

Obstructive sleep apnea (OSA) is a highly prevalent and underdiagnosed sleep disorder with significant cardiovascular implications, namely in atrial fibrillation (AF) patients. Despite its clinical relevance, OSA prevalence among AF patients and the diagnostic strategies used remain heterogeneous across studies, complicating screening, and treatment pathways. Our aim was to synthesize recent evidence on OSA prevalence in AF populations and to critically evaluate the diagnostic methods and screening strategies employed in clinical studies, by conducting a systematic review using PubMed and Google Scholar to identify original clinical studies published between January-2019 and December-2024. Inclusion criteria targeted adult AF populations assessed for OSA or sleep-disordered breathing. The results were analyzed by two independent reviewers. Non-concordances were resolved by consensus. Data extracted included study characteristics, population profiles, diagnostic approaches, prevalence rates, symptom profiles, and clinical correlates. Thirty-eight studies were included, comprising predominantly observational studies. Prevalence estimates of OSA in AF populations ranged from 5% to 90%, with most studies reporting rates >60%. A consistent burden of moderate-to-severe OSA was observed. Diagnostic methods varied widely, from polysomnography (PSG) and home sleep apnea testing to pacemaker-derived monitoring and questionnaires such as STOP-Bang and Epworth Sleepiness Scale (ESS). Underdiagnosis was attributed to minimal symptomatology, lack of physician awareness, and reliance on subjective tools. Several studies highlighted the limited sensitivity of standard screening instruments in AF populations and advocated for objective testing even in asymptomatic patients. Marked heterogeneity in study designs, diagnostic methods, and populations precluded quantitative synthesis and limited direct comparisons. Objective diagnostic testing, particularly PSG, is essential to improve OSA detection rates and guide individualized management. Integration of structured screening protocols into AF care—especially for high-risk patients—and interdisciplinary collaboration are critical. Full article