Medical sciences (Basel, Switzerland)最新文献

Background/Objectives: Sexual dysfunction (SD) and broader sexual health problems are common after neurological disorders, yet interventional evidence is fragmented across conditions and outcomes. This umbrella review mapped and appraised systematic review-level evidence on interventions targeting SD and sexual health in neurological populations and qualified conclusions using certainty of evidence. Methods: PubMed, Web of Science, Cochrane Library, Embase, PsycINFO, EBSCOhost, and Scopus were searched from inception to 27 November 2025. Two reviewers screened records, extracted data, assessed review quality with AMSTAR 2, and rated certainty across intervention-outcome pairings using a GRADE-informed approach that integrated review confidence and primary-study risk-of-bias as reported by the source reviews. Results: Twenty-six systematic reviews were included. Overall confidence was frequently limited (17/26 critically low and 6/26 low), with only a small subset rated moderate or higher. Evidence was most coherent for phosphodiesterase type 5 (PDE5) inhibitors improving erectile function in men with spinal cord injury, whereas most other interventions and outcomes were supported by low or very low certainty. Women were represented in 16/26 reviews, yet validated female sexual function outcomes were synthesized in 6/26 reviews and relationship/couple outcomes in 3/26; furthermore, 10/26 reviews restricted inclusion to men, and no review synthesized pediatric intervention trials. Conclusions: Evidence supports PDE5 inhibitors for improving erectile function in men with spinal cord injury, while evidence for other interventions and sexual health domains remains limited. Methodological limitations highlight the need for more inclusive trials, broader standardized outcomes, and longer follow-up within neurorehabilitation pathways.

Background/objectives: Lactate, traditionally considered a byproduct of anaerobic metabolism, is increasingly recognized as a biomarker of tissue perfusion and systemic stress. While hyperlactatemia is frequent after pediatric cardiac surgery, evidence regarding its prognostic role remains controversial. This study aimed to evaluate whether serial lactate measurements predict mortality in children undergoing surgery for congenital heart disease in Southeast Mexico.

Methods: We conducted a retrospective cohort study including children aged 0-210 weeks with confirmed congenital heart disease who underwent first-time cardiac surgery between January 2022 and December 2024. Serum lactate was measured intraoperatively, at intensive care unit (ICU) admission, and at 12 and 24 h postoperatively using a Gem^® Premier™ 3500 analyzer. Sociodemographic, clinical, and surgical data were recorded. Associations between lactate levels and mortality were analyzed with Cox regression, adjusting for RACHS-2 category and intraoperative complications. Predictive performance was assessed with ROC curves and Harrell's C-index.

Results: 103 patients were included (median age 49.2 weeks; 60% female). Lactate levels overlapped intraoperatively but significantly discriminated against survivors from non-survivors thereafter. ICU admission lactate ≥ 4.2 mmol/L predicted mortality with 100% sensitivity and 60% specificity (AUC = 0.84). Hazard ratios confirmed that lactate at ICU admission (HR 2.17, 95% CI 1.16-4.06; p = 0.015), 12 h (HR 6.37, 95% CI 1.02-39.6; p = 0.047), and 24 h (HR 1.81, 95% CI 1.07-3.09; p = 0.028) were significant predictors of mortality. The model showed excellent discrimination (Harrell's C = 0.986), though optimism due to the limited number of deaths should be considered.

Conclusions: Serial lactate monitoring, particularly upon ICU admission, provides strong prognostic information for in-hospital mortality in pediatric cardiac surgery patients. Incorporating early postoperative lactate into routine monitoring may allow timely therapeutic adjustments. Preoperative lactate assessment warrants further evaluation as a potential risk stratification tool.

Background/Objectives: Adolescent idiopathic scoliosis (AIS) is a three-dimensional deformity of the spine with multifactorial etiology. Its treatment is conservative and/or surgical. The most commonly used conservative method is a full-time brace. However, nighttime braces have recently gained prominence, offering improved tolerance and a positive impact on health-related quality of life. The main objective of this study was to conduct a narrative review of published articles comparing the effectiveness of Providence nighttime versus full-time brace use to determine whether nighttime use is an effective option for improving therapeutic adherence, health-related quality of life, and psychosocial impact. Methods: A scientific literature search was conducted using the Scopus and PubMed databases. We searched for randomized controlled trials (RCTs), meta-analyses, systematic reviews and retrospective comparative studies reported in English from 2019 to 2024. The literature search was conducted from October to April 2024. Different combinations of the terms and MeSH terms "adolescent", "idiopathic", "scoliosis", "Providence", "full-time" and "brace" connected with various Boolean operators were included. Results: Overall, 70 articles were reviewed from the selected database. After removing duplicated papers and title/abstract screening, 10 studies were included in our review. The results showed that nighttime brace use has similar results in terms of effectiveness to full-time brace use in mild to moderate curves. However, nighttime brace use improves therapeutic adherence, health-related quality of life and psychosocial impact. Nevertheless, the effectiveness of night braces depends on factors such as curve type, magnitude, and bone maturity. So, in patients with moderate-severe curves and high growth velocity, it is important to reconsider the type of brace, as in these cases night braces alone may be ineffective in slowing the progression of the curve. Conclusions: Providence nighttime brace could be an effective treatment and better tolerated alternative to full-time brace in specific cases. This approach could improve therapeutic adherence. Nevertheless, more controlled and homogeneous studies are needed to establish definitive recommendations.

Background/Objectives: Pediatric patients with primary headaches frequently exhibit diverse comorbid conditions, often rendering their headaches intractable. Early identification of and intervention for comorbid conditions are crucial for improving prognosis, yet remain challenging. We hypothesized that headache onset timing can predict the presence of these comorbid conditions. Methods: Headache onset timing of 106 pediatric patients (aged 6-17 [median: 13] years) with migraine or tension-type headache and associated comorbidities, including neurodevelopmental and sleep disorders, orthostatic intolerance (OI), and psychosocial factors, was retrospectively analyzed. Results: Headache onset timing was most frequent upon awakening (33.0%), followed by indeterminate (31.1%) and orthostatic (20.8%) onsets. OI (40.6%) and psychosocial factors (38.7%) were the most prevalent comorbid conditions. Psychosocial factors were most common in the awakening (62.9%) and indeterminate (27.3%) onset groups; OI predominated in the orthostatic group (77.3%). Multivariate analysis revealed that psychosocial factors were a significant risk factor for awakening headache (odds ratio [OR]: 4.59, 95% confidence interval [CI]: 1.80-11.71). OI was a risk factor for orthostatic onset headache (OR: 7.18, 95% CI: 1.92-26.87) and inversely associated with indeterminate headache (OR: 0.15, 95% CI: 0.04-0.54). Conclusions: Our findings suggest that detailed classification of headache onset timing can predict potential risks of specific comorbid conditions in pediatric patients.

Background/Objectives: Obesity-associated hyperleptinemia has been linked to breast cancer (BC) progression via mechanisms that remain incompletely understood. This study explores the role of leptin and its receptor (LEPR) in facilitating BC cell proliferation, migration, epithelial-mesenchymal transition (EMT), and STAT3 signaling pathway activation. Methods: We analyzed gene expression and survival data from TCGA BRCA dataset. MCF-7 and MDA-MB-231 BC cells were exposed to leptin at 10 ng/mL (lean-associated levels) and 100 ng/mL (elevated levels linked to obesity). MTT assays, colony formation tests, wound-healing and tumor spheroid dissemination experiments evaluated cell proliferation and migration. Immunofluorescence and Western blot analysis assessed changes in EMT markers and cytoskeletal alterations, while Western blotting and qPCR assessed STAT3 and NCOA1 expression and activation levels. Results: Elevated LEPR expression was linked with unfavorable prognosis in BC patients. Higher doses of leptin (100 ng/mL) significantly enhanced cellular proliferation rates and migratory capabilities, in both cell lines, and promoted EMT characteristics marked by downregulated E-cadherin and cytoskeleton structural changes. Whereas heightened JAK2/STAT3 signaling correlated with elevated leptin dosages, STAT3 inhibition using AG490 reversed leptin-induced migration while reinstating E-cadherin levels to baseline. Furthermore, leptin upregulated NCOA1, an essential STAT3 coactivator, facilitating increased expression of Cyclin D1 and VEGF target genes. Clinical positive relationships were seen between LEP/LEPR expressions and NCOA1 levels and between NCOA1 and various gene signatures related to STAT3/P-STAT3 within BC specimens. Conclusions: Obesity-associated hyperleptinemia enhances aggressiveness in BC through a mechanism involving LEPR-mediated activation pathways encompassing NCOA1/STAT3, which drive proliferation, migration, and EMT. This assigns a potential therapeutic utility for obesity-related advancements found within BC pathology.

Background: The clinical applicability of large language models (LLMs) in high-stakes cardiac emergencies remains unexplored. This study evaluated how well advanced LLMs perform in managing complex catheterization laboratory (Cath lab) scenarios and compared their performance with that of interventional cardiologists. Methods and Results: A cross-sectional study was conducted from 20 June to 2 December 2024. Twelve challenging inferior myocardial infarction scenarios were presented to seven LLMs (ChatGPT, Gemini, LLAMA, Qwen, Bing, Claude, DeepSeek) and five early-career interventional cardiologists. Responses were standardized, anonymized, and evaluated by thirty experienced interventional cardiologists. Performance comparisons were analyzed using a linear mixed-effects model with correlation and reliability statistics. Physicians had an average reference score of 80.68 (95% CI 76.3-85.0). Among LLMs, ChatGPT ranked highest (87.4, 95% CI 82.5-92.3), followed by Claude (80.8, 95% CI 75.7-85.9) and DeepSeek (78.7, 95% CI 72.9-84.6). LLAMA (73.7), Qwen (66.2), and Bing (64.3) ranked lower, while Gemini scored the lowest (59.0). ChatGPT scored higher than the early-career physician comparator group (difference 6.69, 95% CI 0.00-13.37; p < 0.05), whereas Gemini, LLAMA, Qwen, and Bing performed significantly worse; Claude and DeepSeek showed no significant difference. Conclusions: This expanded assessment reveals significant variability in LLM performance. In this simulated setting, ChatGPT demonstrated performance comparable to that of early-career interventional cardiologists. These results suggest that LLMs could serve as supplementary decision-support tools in interventional cardiology under simulated conditions.

Cholangiocarcinoma (CCA) is a highly aggressive cancer of the biliary tract, distinguished by significant intratumoral heterogeneity (ITH), which contributes to therapy resistance and unfavorable clinical outcomes. Traditional genome profiling has revealed recurring driver changes in CCA; yet, genomic data alone fails to elucidate functional pathway activation, adaptive signaling, and the diverse treatment responses reported among tumor locations and disease subtypes. This review analyses the use of integrated sequencing technologies, proteogenomics, and phosphoproteomics to systematically characterize intratumoral heterogeneity in cholangiocarcinoma and convert molecular diversity into therapeutically applicable discoveries. We present evidence that the combination of genomic sequencing and mass spectrometry-based proteomics facilitates the direct correlation of genetic mutations with protein expression, post-translational modifications, and signaling system activity. Phosphoproteomic profiling specifically offers functional insights into kinase-driven networks that dictate tumor aggressiveness, therapeutic susceptibility, and adaptive resistance mechanisms, which cannot be anticipated only from DNA-level analysis. We propose that integrating proteogenomic and phosphoproteomic analyses into diagnostic and therapeutic assessments can enhance molecular classification, reveal subtype- and region-specific therapeutic dependencies, and guide rational combination treatment strategies, based on recent extensive proteogenomic studies and functional proteomic investigations in CCA. Pathway-level analysis of intratumoral heterogeneity provides a framework for selecting targeted medicines, predicting resistance, and informing personalized treatment strategies in CCA. The combination of sequencing, proteogenomics, and phosphoproteomics is essential for advancing precision oncology in cholangiocarcinoma. The implementation of this multi-layered analytical approach may better patient classification, refine therapy choices, and eventually improve clinical outcomes for individuals with this particular heterogeneous cancer.

Objective: This was a longitudinal study of TCF4 CTG18.1 trinucleotide repeat lengths in 17 patients (27 eyes) diagnosed with Fuchs' endothelial corneal dystrophy (FECD), and it aimed to correlate the repeat expansion status with disease severity and progression. Design: This was a prospective cohort study looking at FECD clinical progression and TCF4 CTG18.1 repeat length expansion status over time. Methods: A total of 27 eyes from 17 patients diagnosed with FECD were recruited. Only eyes with FECD disease severity of at least Grade 4 on the modified Krachmer clinical grading scale were included; eyes that had previously undergone any form of ocular surgery prior to the first genotyping or during the duration of follow-up were excluded. CTG trinucleotide repeat genotyping was performed on peripheral blood leukocytes at two time points over an average follow-up of 10 years. Over the follow-up period, the FECD progression of each subject was examined using pachymetry, Scheimpflug imaging (Pentacam), and endothelial cell density (ECD) readings, during the baseline visit, yearly thereafter, at the time of repeat CTG18.1 genotyping, and at their latest visit. Main Outcome Measures: The clinical progression of FECD patients was assessed using central corneal thickness (CCT), ECD, and any keratoplasty performed. CTG repeat length was assessed twice over the entire follow-up period. Results: The non-expanded alleles were shown to be stable over the period of follow-up and did not develop any expanded repeats. Repeat expansion did not influence the risk of attaining Threshold Disease, although more patients in the L ≥ 40 group (CTG18.1 repeat sequence of more than or equal to 40 repeats) underwent keratoplasty. Conclusions: Through this study, we found that the CTG18.1 allele lengths of <40 repeats in peripheral blood leukocytes showed minimal change over a 10-year period, and none became an expanded repeat. Hence, a single CTG expansion assessment, performed at any point in a patient's lifetime, is likely a good representation of genetic risk. Clinicians may use this information to better advise patients on the risk of clinical progression and the best therapeutic strategy.

Background/Objectives: Migraine is frequently comorbid with Meniere's disease, which may complicate interpretation of inner ear imaging and clinical diagnosis. While endolymphatic hydrops has been studied in Meniere's disease and vestibular migraine separately, comparative imaging data for Meniere's disease patients with and without migraine remain limited. Methods: We retrospectively analyzed 78 patients with definite Meniere's disease who underwent endolymphatic contrast-enhanced MRI (HYbriD of Reversed image of Positive endolymph signal and native image of positive perilymph signal; or "HYDROPS"). Patients were classified as Meniere's disease only group (n = 56), or Meniere's disease with migraine (n = 22). The degree of endolymphatic hydrops (negative, mild, or significant) was assessed separately in the inner ear, the cochlea, and the vestibule. Results: In Meniere's disease group, the affected ear consistently showed higher rates of significant endolymphatic hydrops compared to the healthy ear across the inner ear, cochlea, and vestibule (p < 0.01). In contrast, Meniere's disease with migraine group showed no significant interaural differences. Meniere's disease with migraine group showed a significantly higher frequency of significant endolymphatic hydrops in the healthy cochlea (p < 0.01). Similar patterns were observed in the inner ear (p < 0.025) and vestibule (p = 0.05), although these differences did not reach statistical significance. Bilateral hydrops was significantly more frequent in Meniere's disease with migraine group than in Meniere's disease group among all regions investigated (p < 0.05). Conclusions: Meniere's disease patients with migraine exhibit a distinct endolymphatic hydrops pattern, characterized by bilateral or symmetrical hydrops and involvement of the healthy ear. These findings suggest migraine-related mechanisms may contribute to endolymphatic hydrops, and bilateral endolymphatic hydrops on endolymphatic contrast-enhanced MRI in suspected Meniere's disease cases should prompt consideration of comorbid migraine, in addition to bilateral Meniere's disease or asymptomatic hydrops.

Background/Objectives. Pentoxifylline (PTF) is an effective treatment to delay the progress of Diabetic Nephropathy; it also has beneficial effects on heart failure, two closely related clinical conditions. However, the simultaneous Nephroprotective and Cardioprotective effects of PTF have not been appropriately analyzed. The objective of this study was to analyze if both effects occur together in Diabetic patients. Material and Methods. A Randomized Controlled Trial was performed to compare Placebo (P-G) vs. PTF (400 mg/8 h) (PTF-G) in patients with CKD stages III-IV (KDIGO) due to Diabetic Nephropathy. Creatinine-Cystatin C-based Estimated Glomerular Filtration Rate (eGFRCysCCr) and Microalbuminuria were evaluated at baseline, six, and twelve months. Echocardiographic assessment of heart morphology and function was performed. Results. Ninety-three patients were available for the final analysis, 52 in the PTF group and 41 in the P group. There were no differences in clinical and biochemical parameters between groups at baseline. At 6 months, microalbuminuria changed 27.96 ± 43.06 in P-G and -30.27 ± 41.48 mg/24 h in PTF-G (p < 0.001), eGFRCysCCr changed -1.55 ± 7.10 in P-G and 1.40 ± 7.28 mL/min/1.73 m² in PTF-G (p = 0.083), and left ventricular mass index (LVMI) changed 10.86 ± 16.40 in P-G and -2.71 ± 19.52 g/m² in PTF-G (p = 0.001). At 12 months, microalbuminuria changed 24.10 ± 43.28 in P-G and -43.18 ± 52.13 mg/24 h in PTF-G (p < 0.001), eGFRCysCCr changed -6.55 ± 10.18 in P-G and 0.98 ± 8.17 mL/min/1.73 m² in PTF-G (p = 0.008), and LVMI changed 20.79 ± 20.06 in P-G and -0.82 ± 25.95 g/m² in PTF-G (p = 0.028). No significant adverse events occurred in any group. Conclusions. Pentoxifylline is a safe and effective treatment with combined Nephroprotective and Cardioprotective effects in advanced diabetic nephropathy.