Diseases (Basel, Switzerland)最新文献

Background/Objectives: Many heart failure (HF) patients exhibit a suboptimal response to cardiac resynchronization therapy (CRT). This study investigated whether sacubitril/valsartan, a drug known to beneficially impact cardiac remodeling, could improve outcomes for patients undergoing CRT implantation. Methods: In this single-center, observational study, 90 HF patients (left ventricular ejection fraction [LVEF] ≤ 35%) receiving a CRT-defibrillator were stratified into a sacubitril/valsartan group (n = 39) and a control group (n = 51). The primary endpoint was a CRT response at 12 months, defined as improvement in New York Heart Association (NYHA) class, left ventricular reverse remodeling (≥15% reduction in left ventricular end-systolic volume [LVESV] or ≥5% improvement in LVEF), and freedom from HF hospitalization. Results: The sacubitril/valsartan group had a significantly higher CRT response rate (87.2% vs. 64.7%, p = 0.016). They also showed greater improvement in the 6 min walk test (p = 0.013), NYHA class (p = 0.017), reduction in LVESV (p = 0.025), and QRS duration (p = 0.005). Multivariable analysis confirmed sacubitril/valsartan as an independent predictor of CRT response (OR = 4.43; 95% CI: 1.33-14.71; p = 0.015). Conclusions: In this study of HF patients receiving CRT, sacubitril/valsartan was independently associated with superior reverse remodeling, enhanced electrical resynchronization, and a higher rate of CRT response. These findings suggest a potential synergistic role for sacubitril/valsartan in optimizing post-CRT outcomes; however, as this was an observational study, they should be considered hypothesis-generating and require validation in larger, randomized controlled trials.

Background: Mucopolysaccharidosis type IIIC (MPS IIIC) is a rare lysosomal storage disorder caused by pathogenic variants in the HGSNAT gene. Data from large patient cohorts remain scarce, particularly in Latin America.

Methods: We retrospectively analyzed clinical, biochemical, and genetic data from patients diagnosed with MPS IIIC through the MPS Brazil Network. Diagnosis was based on reduced activity of acetyl-CoA:α-glucosaminide N-acetyltransferase (HGSNAT), elevated urinary glycosaminoglycans (uGAGs), and/or molecular genetics tests.

Results: A total of 101 patients were confirmed with MPS IIIC, representing one of the largest cohorts worldwide. Females accounted for 60% of cases. The mean age at symptom onset was 5.4 ± 3.9 years, while the mean age at diagnosis was 11.7 ± 6.9 years, reflecting a 6-year diagnostic delay. Most patients initially presented with developmental delay (82%) and facial dysmorphism (80%), whereas behavioral manifestations were less frequently identified (25%), suggesting a milder phenotype than previously reported. Genetic information was available for 28% of patients, showing recurrent alleles (c.372-2A>G, c.252dupT) and several novel mutations, which expand the mutational spectrum of the disease. Genotype-phenotype similarities with Portuguese, Italian, and Chinese cases suggest shared ancestry contributions. Regional differences included earlier diagnoses in the North of Brazil and high consanguinity rates in the Northeast region.

Conclusions: This study describes the largest Brazilian cohort of MPS IIIC, documenting novel variants and regional heterogeneity. Findings highlight diagnostic delays, ancestry influences, and the urgent need for disease-modifying therapies.

Purpose: Previous data showed an increased risk of developing urinary incontinence in breast cancer patients. However, there is a lack of studies including both pre and postmenopausal women. The aim of this study was to analyze the incidence of subsequent urinary incontinence in breast cancer patients and variables associated with an increased urinary incontinence.

Methods: This study utilized IQVIA Disease Analyzer database to examine the five-year cumulative incidence of urinary incontinence among 68,066 women diagnosed with breast cancer in gynecological practices in Germany between January 2005 and December 2021 by using Kaplan-Meier curves, stratified by age group. Multivariable Cox regression models were conducted to assess the association between age, co-diagnoses, and endocrine therapy (tamoxifen, aromatase inhibitors) and incident urinary incontinence.

Results: Within five years of the start of follow-up, 5.8% of women were diagnosed with urinary incontinence. Age (HR = 1.36; 95% CI = 1.21-1.54 for age 51-60; HR = 2.06; 95% CI = 1.84-2.31 for age group 61-70 and HR = 2.71; 95% CI = 2.42-3.04 for age group >70 as compared to age group ≤50), depression (HR = 1.41; 95% CI: 1.25-1.59) and menopausal and other perimenopausal disorders (HR = 1.21; 95% CI: 1.10-1.27) were associated with an increased urinary incontinence risk. The association was negative and statistically significant for aromatase inhibitor therapy (HR = 0.71; 95% CI: 0.66-0.78) as compared to women without endocrine therapy, whereas tamoxifen therapy was not associated with decreased or increased urinary incontinence risk.

Conclusions: In conclusion, this study reports an 5.8% incidence of urinary incontinence within five years after breast cancer diagnosis. Age-related differences and co-diagnoses should be taken into account.

Maximal fat oxidation (MFO) rate and the intensity at which it occurs (Fatmax) are key indicators of metabolic flexibility, yet their assessment in obese populations poses methodological challenges. This scoping review synthesizes evidence from 23 studies investigating protocols for determining Fatmax and MFO during cycle ergometry. Across studies, obese and sedentary participants followed testing procedures, typically involving lower initial workloads, smaller workload increments, and longer stage durations than those used for fitter individuals. In obese populations, Fatmax generally occurred at 30-50% of VO₂ peak, compared with values exceeding 60% in trained participants. While the reliability of Fatmax was acceptable, greater variability was observed for MFO rate. Fitness level appeared to exert a stronger influence than adiposity on fat oxidation, with obesity often associated with a left-shifted fat oxidation curve. Additional factors such as gender, developmental stage, insulin resistance, and type 2 diabetes further modulated these responses. Importantly, short-term training interventions, including moderate-intensity exercise, high-intensity interval training, and Fatmax-targeted protocols, consistently enhanced MFO and shifted Fatmax toward higher intensities, with favorable effects on insulin sensitivity and metabolic health. In contrast, nutritional and supplementation studies provided limited evidence of additional benefits. Overall, Fatmax assessment is feasible in obese populations when appropriate methodological adjustments are applied, and exercise interventions can rapidly enhance fat oxidation capacity. Future research should focus on protocol standardization, mechanistic exploration, and long-term interventions to clarify the role of Fatmax in obesity management and its potential clinical applications.

Background: Ulcerative colitis (UC) is a chronic, relapsing inflammatory bowel disease that requires regular monitoring. The University of Alberta IBD Unit piloted a proactive outreach protocol for biologic-naïve UC patients, including clinical and biochemical variables, and assessed its impact on UC care.

Methods: Biologic-naïve UC patients without follow-up for ≥6 months were recruited by phone and completed Partial Mayo, modified Sutherland Index, and MARS-5 questionnaires, as well as blood work and fecal calprotectin (FCP). Results were sent to each patient's gastroenterologist, who then completed a survey about intended UC management changes.

Results: 81 patients completed the protocol. UC management was changed in 45 (55.6%) cases, with 82.2% of changes being expedited follow-up or management escalation. Six patients had active flares, and 17 with asymptomatic inflammation were identified. 23 patients underwent endoscopy, with 10 (43.4%) showing active disease. Six patients started biologic therapies based on protocol and endoscopic findings. UC management escalations were significantly predicted by FCP and Sutherland Index scores on logistic regression analysis. 86.4% of gastroenterologists rated the protocol helpful.

Conclusions: Patient care can be improved by a one-time, proactive outreach program for biologic-naïve UC. Outreach and monitoring in biologic-naïve UC should include assessment of both FCP and clinical markers to improve UC management.

Background: Hypertrophic cardiomyopathy (HCM) is the most common inherited cardiac disease. Arterial hypertension represents the leading modifiable risk factor for cardiovascular morbidity and mortality globally. Their coexistence is frequent, affecting approximately 40-60% of adults with HCM, yet the implications of this overlap remain insufficiently investigated.

Methods: We conducted a narrative review of the existing literature addressing the clinical profile and management strategies in patients with concomitant HCM and hypertension. Particular emphasis was placed on pharmacologic treatment and the role of emerging therapies for this population.

Results: Patients with both conditions are generally older, with more cardiometabolic comorbidities and greater functional limitation than those with isolated HCM. Hypertension may confound diagnosis and is linked to a higher prevalence of atrial fibrillation and stroke. Its effect on ventricular arrhythmias, sudden cardiac death and mortality is less clear. Management is challenging, as vasodilatory antihypertensives can exacerbate left ventricular outflow tract obstruction. β-blockers and non-dihydropyridine calcium channel blockers are preferred, while novel agents such as myosin inhibitors and SGLT2 inhibitors show potential but require further study.

Conclusions: The coexistence of HCM and hypertension is frequent but insufficiently studied, with major implications for diagnosis and treatment. Further research is essential to optimize management and outcomes.

Background: Oral mucositis (OM) is a significant complication after allogeneic stem cell transplantation.

Objectives: This prospective, observational cohort study assessed the effectiveness of a polyvinylpyrrolidone-zinc gluconate and taurine (PVP-ZG-TAU) oral gel in managing OM. The primary objective was to determine whether the gel reduced the incidence and grade of OM and accelerated its resolution.

Methods: The study enrolled 82 patients; 39 received the PVP-ZG-TAU gel, and 43 represented a historical control group. To prevent oral mucositis, both groups maintained good oral hygiene. In the experimental group, patients received three sprays of PVP-ZG-TAU gel, three times a day, from the start of conditioning chemotherapy until day +15 after allo-SCT.

Results: In the PVP-ZG-TAU group, 79.1% patients experienced grade 1-2 OM and 20.9% experienced grade 3-4 OM. In the control group, 74.4% had grade 1-2 OM, and 25.6% had grade 3-4 OM (p = ns). Resolution occurred significantly faster in the PVP-ZG-TAU group, with an 84% resolution rate per 100 person-weeks, compared with 62% in the control group. Cox regression analysis revealed that treatment was associated with a 68% greater likelihood of earlier resolution (adjusted hazard ratio [HR], 1.68; 95% confidence interval [CI], 1.03-2.74; p = 0.036).

Conclusions: These findings suggest that PVP-ZG-TAU can reduce OM duration and serve as a supportive intervention for allo-SCT patients.

Background: Non-communicable diseases (NCDs) such as cardiovascular diseases, diabetes, obesity, and cancer are the leading cause of mortality globally and in Saudi Arabia, accounting for more than 70% of all deaths. Despite national initiatives offering free preventive services, screening uptake remains low. This study aimed to describe the demographic and clinical characteristics of individuals participating in community-based NCD screening campaigns in the Eastern Province of Saudi Arabia and to evaluate screening uptake, compliance, and diagnostic outcomes.

Methods: A retrospective cross-sectional analysis was conducted among 3106 adults screened at volunteer-driven community campaigns held between January 2023 and December 2024. Screening included anthropometric measurements, blood pressure assessment, and glucose testing, followed by eligibility evaluation for osteoporosis and cancer screening. Uptake and compliance were verified using electronic health records. Descriptive and inferential statistical analyses were applied.

Results: Participants were 64% male and 36% female, with a mean age of 41.4 ± SD years. Obesity, hypertension, and diabetes were identified in 32%, 31%, and 12% of participants overall. Gender-stratified prevalence showed higher obesity among females at 36% (95% CI 32.3 to 38.1) and higher hypertension and diabetes among males at 36% (95% CI 34.0 to 38.2) and 14% (95% CI 12.1 to 15.2), respectively. Uptake among eligible individuals was 51% for dual-energy X-ray absorptiometry (DEXA), 47% for fecal immunochemical testing (FIT), 43% for Pap smear, and 39% for mammography. Diagnostic findings demonstrated substantial undetected disease burden, including osteoporosis in 41% (95% CI 26.0 to 56.8) of DEXA scans, a FIT positivity rate of 5% (95% CI 1.5 to 10.3), abnormal Pap cytology in 3% (95% CI 1.1 to 7.5), and BI-RADS 0 mammograms in 19% (95% CI 11.9 to 29.5), reflecting incomplete assessments requiring further evaluation.

Conclusions: Community-based campaigns can effectively resolve limited engagement in health promotional activities and detect substantial burdens of undiagnosed NCDs. However, improvements in referral tracking, follow-up systems, and culturally tailored health education are essential to enhance screening compliance and early detection outcomes. These results can be utilized to inform public policies by extending screening services to additional areas, increasing investment in preventive health campaigns, and enhancing the capacity of the health system.

Background: Patients with EGFR-mutated non-small cell lung cancer (NSCLC) respond well to EGFR tyrosine kinase inhibitors (TKIs), but current EGFR mutation profiling relies on invasive tumor biopsies. Developing less invasive approaches, particularly proteomic evaluation of circulating tumor cells (CTCs) for EGFR mutation profiling, remains crucial.

Methods: A flow cytometry method for detecting EGFR^L858R-bearing CTCs was established by spiking NCI-H1975 cells into blood from cancer-naive donors. The method was then applied to blood samples from 21 NSCLC patients and 10 cancer-naive donors.

Results: The gating strategy was defined by CD45^-CK-7/8⁺CK-14/15/16/19^-EpCAM⁺vimentin⁺EGFR^L858R, with a cut-off value of 5 cells/mL. The method yielded positive results in all seven patients with the EGFR^L858R mutation and negative results in all ten cancer-naive donors. Compared to the PCR-based reference method, the approach showed 100% positive and 71% negative agreement. Crucially, our in-house method detected EGFR^L858R-bearing CTCs in three patients initially identified as EGFR wild-type and one patient with a different EGFR mutation. The remaining samples were concordant with PCR. Notably, two patients with these discordant results received EGFR-TKIs and experienced partial responses.

Conclusions: This study introduces a feasible, less invasive proteomic approach for binarily detecting EGFR mutations in CTCs, offering a novel means for patient identification.

Central nervous system (CNS) cryptococcosis caused by Cryptococcus neoformans is a severe opportunistic infection that primarily affects individuals with impaired cellular immunity. Although the classic presentation includes headache, fever, and meningeal signs, chronically immunosuppressed patients may develop atypical neuropsychiatric manifestations, leading to diagnostic delays. We report the case of a 53-year-old man with rheumatoid arthritis (RA) receiving long-term prednisolone and etanercept therapy, who presented with a 7-day history of depressive mood, anhedonia, social withdrawal, irritability, and progressive confusion. Neurological examination revealed disorientation without focal deficits. Brain imaging showed only mild cortical atrophy, and cerebrospinal fluid (CSF) analysis revealed lymphocytic pleocytosis, low glucose, and elevated protein levels. Multiplex PCR (FilmArray^®) of CSF identified Cryptococcus neoformans, CSF positive to C. neoformans. The patient was treated with liposomal amphotericin B followed by fluconazole, resulting in gradual improvement of both neurological and psychiatric symptoms. This case highlights an unusual presentation of CNS cryptococcosis in a non-HIV immunosuppressed patient with RA, emphasizing that acute psychiatric or cognitive changes can be the predominant manifestation. Clinicians should consider fungal infections in the differential diagnosis of acute neuropsychiatric symptoms in patients receiving chronic corticosteroid and biologic therapy. Early recognition and molecular diagnosis can facilitate timely antifungal treatment, potentially improving prognosis and reducing morbidity associated with delayed therapy. This report underscores the importance of awareness of atypical presentations of opportunistic infections in immunosuppressed populations.