Medical sciences (Basel, Switzerland)最新文献

Background: People with HIV (PWH) experience increased cardiovascular disease driven by chronic inflammation despite suppressive antiretroviral therapy. Circulating microRNAs (miRNAs) have emerged as potential biomarkers of cardiometabolic dysfunction, yet their relevance to HIV-associated atherosclerosis remains unclear.

Methods: We analyzed PWH PBMC-derived miRNAs in two independent cohorts: the HUMT cohort (N = 185), characterized by carotid ultrasound assessment of atheroma plaque and carotid intima-media thickness (cIMT), and the CoRIS cohort (N = 119), stratified by cardiometabolic comorbidity burden (≥3 comorbidities vs none). An exploratory miRNA microarray comparing individuals with and without atheroma plaque (AP+ vs. AP-, N = 72) identified candidate miRNAs, a subset of which was selected for validation by RT-qPCR. Associations with atherosclerosis, cardiometabolic comorbidities and the HIV-adapted COMVIH-CoR clinical cardiovascular risk score were examined.

Results: Forty-four miRNAs were differentially expressed in AP+ vs. AP- in the microarray. RT-qPCR validation showed sex-specific miRNA association with miR-638 was consistently downregulated in AP+ and pathological cIMT among men, while reduced expression of miR-27b-5p and miR-3613-5p was observed in women. Associations between miRNAs and cardiometabolic comorbidities differed by cohort: in HUMT, miR-638 was reduced in diabetes and obesity, while miR-140-5p and miR-27b-5p were decreased in smokers and individuals with low HDL. CoRIS participants with multiple comorbidities showed a generalized miRNAs upregulation. Notably, miR-140-5p was consistently elevated in individuals with high COMVIH-CoR scores across both cohorts.

Conclusions: PBMC-derived miRNAs capture heterogeneous, context-dependent dimensions of cardiovascular risk in PWH, likely reflecting cumulative immune-metabolic stress rather than universal diagnostic markers of subclinical atherosclerosis and supporting a phenotype-specific role.

Objectives: To evaluate the effectiveness of zinc oxide (ZnO) ointments versus non-irritant barrier films (NIBFs) in the prevention of Incontinence-Associated Dermatitis (IAD). Specific objectives included analyzing the effects of treatment over time, establishing when IAD appears in each group, and determining the safety and cost-effectiveness of both treatments.

Methodology: A multicenter prospective cohort study was carried out in 10 social health centers in Spain. The final sample included 164 older institutionalized patients with urinary and/or mixed incontinence, divided into two cohorts (79 with ZnO and 85 with NIBF). Follow-up lasted for six weeks. Validated scales were used for data collection, such as the Categorization of Moisture-Associated Skin Damage (MASD) of the GNEAUPP (National [Spain] group for the assessment of pressure ulcers and chronic wounds) and the Visual Erythema Scale (VES).

Results: The overall incidence of IAD was 20.7% in the sample during follow-up. No statistically significant difference in effectiveness was found between ZnO (27.8% incidence of IAD) and NIBF (32.9% incidence of IAD) in preventing IAD (p = 0.479). However, survival analysis suggested that the onset of IAD is delayed more in the NIBF group. No adverse events or side effects were reported attributable solely to the use of the products. When considering the total cost per process (including staff application time), ZnO ointment was EUR 0.02 more expensive per patient per day than NIBFs.

Conclusions: Although both products have similar efficacy and safety, NIBFs delay the onset of IAD more than ZnO. In addition, despite a higher unit price, NIBFs are more cost-effective per procedure because of savings in nursing time during application and removal.

Background: Hypothermic oxygenated perfusion (HOPE) has emerged as a promising preservation strategy before liver transplantation, mitigating ischemia-reperfusion injury and improving graft function, especially in marginal grafts and donors after cardiac death.

Methods: This is a prospective monocentric study; 34 HOPE-treated liver grafts were enrolled and analyzed through histopathology and RT-PCR to assess endothelial-related gene expression and its correlation with post-transplant outcome. The aim of the present study was to assess the relationship between the expression of genes related to vascular activation and homeostasis and post-transplant clinical characteristics.

Results: Expression of SMA and TGF-β1 was significantly associated with arteriolar myointimal thickening of the graft (p = 0.007 and 0.068). Higher expression of SMA, ERG, and TGF-β1 was correlated with a shorter post-operative intensive care stay (p = 0.070, p = 0.010 and p = 0.029, respectively), particularly with post-transplant acute kidney injury.

Conclusions: These findings highlight the role of endothelial activation and vascular homeostasis for an early recovery after liver transplantation, posing an important issue for healthcare systems as well, and suggesting molecular markers for graft assessment and risk stratification.

Metabolic dysfunction-associated steatotic liver disease (MASLD) is the most common liver disease worldwide, with an estimated global prevalence of 38% in adults. MASLD confers a significant increase in morbidity and mortality due to its association with cardiovascular disease and progressive liver disease, including cirrhosis and hepatocellular carcinoma. Current treatment paradigms for MASLD are centred around lifestyle modification and weight loss, with a need for pharmacotherapeutic options. Given the strong relationship between MASLD and cardiovascular disease, there is an interest in evaluating the efficacy and safety of cardiovascular medications such as statins in liver disease. Statins are the most commonly prescribed lipid-lowering medication in the world, with an established role in reducing cardiovascular morbidity and mortality. Statins are currently under-prescribed in the MASLD patient population, yet there is growing interest in determining whether statins could be utilised to treat MASLD itself. This comprehensive review aims to explore the evidence regarding the use of statin therapy for conventional, lipid-lowering indications in patients with MASLD and its potential benefits for the treatment of MASLD and its complications.

Background: Parkinsonism entails pronounced basal ganglia dysfunction, but emerging research suggests that broader subcortical networks, specifically the cerebellum, play a vital role in functional motor compensation following circuit-level destabilization. This study sought to characterize the electrophysiological dynamics of Multi-Unit Activity (MUA) amplitude in Crus II, the dentate nucleus (DN), and the inferior olive (IO) following a focal mechanical lesion of the ventrolateral striatum (VLS) as a circuit-level perturbation model during spontaneous behaviors. Methods: Bilateral mechanical VLS lesions were induced in 24 male Wistar rats. MUA signals were chronically recorded over a four-week protocol during self-grooming, horizontal locomotion, and rearing behaviors. Results: Crus II and the IO exhibited a structure-specific "dynamic transition," shifting from early-stage hyperexcitability to significant late-stage attenuation by W4 (p < 0.001), reflecting a divergence from control trajectories rather than internal temporal drift within the lesioned state. Conversely, the DN showed sustained hypoactivity compared to healthy controls throughout the recording period (p < 0.05). Despite these robust neurophysiological shifts, the syntactic organization of grooming and exploratory patterns remained phenotypically preserved, indicating functional sufficiency despite underlying circuit noise. Conclusions: VLS injury triggers a rapid distributed reorganization across the striato-cerebellar network. The cerebellum acts as an active adaptive node, recalibrating internal network gain to mask early Parkinsonian-like circuit dysfunction at the level of functional sufficiency and maintain motor performance through active homeostatic gain regulation.

Background: Inhaler device changes at hospital discharge should address patient capacity yet often reflect routine. We evaluated the appropriateness of these decisions and their impact on clinical outcomes. Methods: In this prospective observational study (N = 480), we assessed patient technical capacity using a composite of critical errors, inspiratory flow, adherence, and knowledge. We stratified patients into 'Need-Positive' and 'Need-Negative' cohorts to quantify patterns of clinical inertia and over-adjustment. Multivariable models identified predictors of decision-making and associations with 30-day outcomes. Results: Device changes were primarily determined by the pre-admission device class (spacers: aOR 0.52; 95% CI 0.28-0.96; p = 0.037) and by the patient's treatment pathway rather than by clinical need. This disconnect generated two types of errors: 38.3% of Need-Positive patients (n = 214) experienced clinical inertia (no corrective action), while 36.8% of Need-Negative patients (n = 266) underwent over-adjustment (unnecessary switching). Inertia perpetuated errors in patients with need, whereas over-adjustment was associated with the emergence of new errors in patients without need. Successful mismatch resolution was associated with a significantly lower 30-day readmission rate (12.1% vs. 32.5%; OR 0.48; 95% CI 0.26-0.88; p = 0.017). Conclusions: Discharge prescribing is driven more by habit than by objective assessment, leading to widespread missed opportunities for correction. Implementing evidence-based protocols to identify and resolve patient-device mismatches may represent a high-impact strategy to reduce readmissions and associated healthcare use.

Background: Intradialytic hypotension (IDH) in hospitalized patients with acute kidney injury (AKI) is associated with increased morbidity and mortality. Early identification of high-risk patients may enable preventive strategies. This study aimed to identify risk factors for IDH and develop a prediction model in this setting. Method: We conducted a retrospective cohort study of hospitalized patients with dialysis-requiring AKI who underwent conventional renal replacement therapy (RRT). Univariable and multivariable analyses were performed using generalized estimating equations (GEE) to account for repeated dialysis sessions within patients. IDH was defined as systolic blood pressure < 90 mmHg during dialysis. Although external validation was not performed, internal validation of the predictive model was conducted using 10-fold cross-validation. Model performance was assessed by calculating the area under the receiver operating characteristic curve (AUROC). Result: A total of 423 hemodialysis sessions from 85 patients were analyzed; the median age was 61 years, and the incidence of IDH session was 35.9%. Multivariable GEE analysis identified residual urine output <100 mL/day (OR 1.78, p = 0.007), vasopressor use (OR 3.36, p < 0.001), prior IDH (OR 2.25, p = 0.002), and lower pre-dialysis mean arterial pressure (MAP 80-89 mmHg: OR 2.43, p = 0.002; MAP < 80 mmHg: OR 2.95, p < 0.001) as significant predictors. Serum albumin < 2.5 g/dL was retained in the final model due to its clinical relevance and contribution to model performance despite borderline significance (OR 1.44, p = 0.08). A weighted integer-based risk score was derived directly from the coefficients of the final multivariable GEE model, stratifying patients into low-, intermediate-, and high-risk groups with IDH incidences of 11.6%, 33.9%, and 56.7%. The model demonstrated good discrimination, with an AUROC of 0.760 (95% CI, 0.714-0.807). Conclusions: The predictive score for IDH demonstrated good performance and highlights the importance of raising awareness to guide interventions aimed at improving the outcomes of hospitalized AKI patients requiring conventional RRT.

Background: Loeys-Dietz syndrome (LDS) is an autosomal dominant aortopathy characterized by aggressive aneurysm formation and arterial dissections. Pregnancy-related outcomes and timing of LDS diagnosis remain poorly characterized. Methods: Demographics, genetic, obstetric, and vascular data was collected from genetically or clinically confirmed individuals with LDS seen at the three Mayo Clinic sites from 2018 to 2025. Aneurysm progression, new aneurysm formation, and arterial dissections were recorded across all vascular beds. Vascular events were assessed during pregnancy, within 12 months postpartum, and during breastfeeding. Comparative analyses were performed between women with and without a history of pregnancy, and a single-arm descriptive analysis was conducted among patients who experienced vascular complications during the peripartum period. Continuous variables were compared using the Mann-Whitney U test, while categorical variables were analyzed using chi-square or Fisher exact tests. Results: Of 47 women with LDS, 24 had a history of pregnancy, accounting for 54 pregnancies. In the comparative analysis, age at LDS diagnosis differed significantly between women with and without a prior pregnancy: women without prior pregnancy were diagnosed at a younger age (median 23.5 years [IQR 10.8-41.0], n = 23) than those who had been pregnant (median 53.5 years [IQR 43.0-59.3], n = 24). Among pregnant women, the median age at first pregnancy was 28 years (IQR 23-34); only 4 (16.7%) knew their diagnosis before pregnancy. Of 54 pregnancies, 40 (74.1%) resulted in live birth, with 23 (57.5%) vaginal and 17 (42.5%) cesarean deliveries; preterm delivery occurred in 1 (2.5%) pregnancy, and postpartum hemorrhage in 2 (5.0%). No maternal deaths, aortic dissections, or uterine ruptures occurred during gestation or the first postpartum year. In addition, 14 women (58.3%) developed aneurysms, 6 (25.0%) experienced at least one arterial dissection, and 7 (29.2%) required surgical repair, predominantly involving the ascending and abdominal aorta. The prevalence of vascular complications did not differ significantly between groups. Conclusions: In this LDS cohort, pregnancy and the early postpartum period were not accompanied by acute aortic catastrophes, despite frequent diagnostic delay. Although women without prior pregnancy were diagnosed at a younger age, the overall burden of vascular and morphologic complications did not differ significantly by pregnancy history. These findings highlight the importance of long-term cardiovascular follow-up in women with LDS.

Background/Objectives: Periprocedural blood pressure influences outcomes after endovascular treatment (EVT), but the impact of pulse pressure (PP) remains unclear. We assessed associations between intraprocedural PP and clinical and radiological outcomes after EVT. Methods: We retrospectively analyzed adults with acute ischemic stroke (AIS) due to proximal anterior circulation large vessel occlusion treated with EVT under general anesthesia. Non-invasive BP was recorded every 5 min during EVT. From these recordings, we derived baseline, maximal, minimal, and median PP, PP variability indices, and cumulative time above predefined PP thresholds. The primary endpoint was poor functional outcome at 90 days (modified Rankin Scale 3-6). Secondary endpoints were final infarct volume (FIV), malignant brain edema (MBE), symptomatic intracranial hemorrhage (sICH), and hemorrhagic transformation (HT). Multivariable regression models were adjusted for established prognostic factors. Results: In the 217 patients included, higher median PP during EVT independently predicted poor functional outcome, larger FIV, MBE, and HT, but not sICH. Longer duration of PP > 50 mmHg was independently associated with poor outcome, MBE, and HT. Among other hemodynamic variables, only a >40% mean arterial pressure (MAP) drop from baseline independently predicted poor outcome. Adding median PP to the baseline multivariable model modestly increased its discriminative ability and significantly improved model fit. Conclusions: In AIS patients with proximal anterior circulation large vessel occlusion treated with EVT under general anesthesia, higher intraprocedural PP and longer exposure to elevated PP are associated with worse functional and radiological outcomes, supporting PP as a potential hemodynamic target alongside avoidance of large MAP reductions.

Background: Recent studies have identified multiple subtypes of non-conventional dysplastic lesions associated with inflammatory bowel disease (IBD). This study aimed to characterise and compare all IBD-associated dysplasias and determine their prevalence within a Southern Hungarian population. Methods: A consecutive cohort of IBD patients between 2011 and 2023 was retrospectively analysed. All available hyper- or neoplastic samples were reclassified according to current pathological criteria. Results: In this 13-year retrospective, single-centre, cohort study, 2396 IBD patients were identified, with 176 possessing samples for re-evaluation. Conventional dysplasia was identified in 130 patients (74%), non-conventional dysplasia in 50 patients (28%), and 33 patients were diagnosed with both (19%). Age (OR = 1.06; 95% CI: [1.03-1.09]; p < 0.001) and male gender (OR = 2.63; 95% CI: [1.07-6.45]; p = 0.032) were associated with higher odds of conventional dysplasia, compared with non-conventional dysplasia. Colorectal carcinoma development and M stage were associated with lower odds of conventional dysplasia: OR = 0.17 ([0.06-0.47]; p < 0.001) and OR = 0.05 ([0.01-0.5]; p = 0.006), respectively. Significant associations were observed with macroscopic appearance (p = 0.013), grade (p = 0.002), localisation (p < 0.001), size (p = 0.016), macroscopic morphology (p = 0.004), grade (p < 0.001), histological subtype (p = 0.001), T stage (p = 0.008) and microsatellite status (p = 0.019). Conclusions: Non-conventional dysplasias were identified in a substantial proportion of neoplastic lesions (50/176; 28%) among IBD patients. These findings highlight the importance of thorough histopathological evaluation to confirm complete resection. Patients with IBD-associated dysplasia, particularly non-conventional types, may benefit from intensified surveillance strategies.