Search Results (311)

Background/Objectives: Moyamoya angiopathy is a progressive occlusive cerebrovascular disorder and a relevant cause of pediatric stroke. While most published data originate from Asian and North American populations, reports from South America remain scarce. This study aimed to characterize the clinical, angiographic, and functional outcomes of pediatric patients with Moyamoya disease (MMD) or Moyamoya syndrome (MMS) who underwent indirect revascularization in a Brazilian cohort, and to contextualize these findings within the international literature. Methods: We retrospectively reviewed all patients under 18 years of age who underwent indirect bypass (EDAS/EDAMS) for MMD or MMS at a tertiary pediatric center in Curitiba, Brazil, between 2009 and 2023. Demographic, clinical, and angiographic data were analyzed, including postoperative Matsushima grading, and functional outcomes assessed by the modified Rankin Scale (mRS) and Glasgow Outcome Scale (GOS). All eligible patients received perioperative aspirin (3–5 mg/kg/day). Results: Fourteen patients (64% female; mean age 9.9 years) were included: 43% with MMD and 57% with MMS. Hemiparesis (86%), seizures (57%), and cognitive impairment (57%) were the most common symptoms. Most were classified as Suzuki stages II–III. All underwent indirect revascularization; 79% received bilateral procedures. Angiographic follow-up (14 hemispheres) showed good collateral formation (Matsushima grade A: 43%; B: 57%). Complications occurred in three patients (21%), and two (14%)—both MMD—developed new postoperative ischemic strokes despite receiving aspirin therapy. At 3.5 years of mean follow-up, the mean mRS was 1.9 ± 0.8 and the GOS was 4.0 ± 0.3. Conclusions: Indirect revascularization in this Brazilian pediatric cohort was feasible and safe, yielding outcomes comparable to international series. Collateral development correlated with functional improvement. These exploratory findings emphasize the importance of early diagnosis, standardized perioperative care, and long-term follow-up, and highlight the need for multicenter collaboration in Latin America. Full article

Background/Objectives: The Parental Stressor Scale: Neonatal Intensive Care Unit (PSS:NICU) is one of the most widely used tools for assessing parental stress in neonatal intensive care settings. This study aimed to translate, culturally adapt and validate the PSS:NICU in a Greek cohort. Methods: A multicenter, cross-sectional study was conducted with 150 parents (89 mothers, 61 fathers; mean age = 34.1 years, SD = 7.2) of hospitalized neonates from three Greek NICUs. The translation followed forward–backward procedures, expert review, and pilot testing. Data were analyzed for internal consistency, factorial validity, and group differences. Results: Confirmatory factor analysis supported the adequacy of the original three-factor structure (Sights and Sounds, Infant Behavior and Appearance, and Parental Role Alteration). Cronbach’s alpha and McDonald’s omega coefficients indicated excellent reliability for the total scale and its subscales. Female participants reported higher stress levels than males in most dimensions. Conclusions: The Greek version of the PSS:NICU demonstrated strong psychometric properties and cultural relevance. This adaptation provides a valid and reliable tool for assessing parental stress in Greek NICUs and facilitates cross-cultural comparisons and the development of targeted psychosocial interventions. Full article

Background/Objectives: Down syndrome (DS) is a neurodevelopmental and neurodegenerative disorder typically caused by trisomy 21. We recently concluded a two-site (Ohio, USA and São Paulo, Brazil), phase-2, randomized trial to evaluate the efficacy, tolerability, and safety of the drug memantine in enhancing cognitive abilities of adolescents and young adults with DS. This trial was a follow-up study to a pilot trial performed in Colorado, USA. Results of these two clinical trials have been published elsewhere. Here, we present a comparative analysis of the baseline neuropsychological assessments at the three sites of these two studies, including their psychometric properties, and an account of the considerations involved in the test battery design. We compared test results in the different sites as a way of evaluating the replicability and generalizability of the test results. The distribution of the test results at each site was analyzed and combined when no differences were detected between the mean values of these results. We used post-treatment data from the placebo arms of these studies to quantify test–retest reliability. Results: Most measures had comparable mean values across test sites, and had good-to-excellent feasibility, few floor effects, and good-to-excellent test–retest reliability. A few measures, however, were deemed unsuitable for use in future studies. Conclusions: This study demonstrated remarkable consistency of results across studies in two countries with significantly different cultures and levels of socioeconomic development, which provides supporting evidence for the future design and implementation of similar multicenter, international clinical studies involving participants with DS. Full article

Background: Age is a well-established determinant of sepsis outcomes, often integrated into severity scoring systems. However, most studies focus on critically ill patients in intensive care units (ICUs), with limited insight into how age influences mortality in non-ICU settings, particularly across the full adult lifespan. Objective: To investigate the relationship between age and in-hospital mortality in patients with sepsis hospitalized in internal medicine wards, using age-stratified logistic and spline regression models. Methods: We conducted a retrospective, multicenter cohort study involving 4300 adult patients admitted to internal medicine wards at eight academic hospitals affiliated with Clalit Health Services in Israel between December 2001 and October 2020. All patients were diagnosed with sepsis during hospitalization and died during their hospital stay. Patients were stratified into seven age groups (18–34, 35–44, 45–54, 55–64, 65–74, 75–84, >85 years). Logistic regression identified age-specific comorbidities associated with mortality. Adjusted spline regression models were used to estimate mortality probabilities across age ranges. Results: The cohort had a mean age at death of 78.84 years, and 51.7% were female. Mortality probability increased with age but demonstrated non-linear trends. Sharp fluctuations in predicted mortality were observed in middle-aged groups (especially ages 45–54), with peaks not captured in conventional binary or linear models. Hematologic and solid neoplasms were strongly associated with mortality in younger groups, while cardiovascular comorbidities such as heart failure and atrial fibrillation were more prominent in older adults. Conclusions: Age is a major determinant of in-hospital mortality in septic patients on internal medicine wards, but its effect is non-linear and age-specific. Our findings highlight a unique population of patients with severe sepsis not managed in critical care settings and underscore the need for more nuanced, age-stratified risk assessment models outside of the ICU. Full article

Objectives: This study aimed to develop and validate a biparametric MRI (bpMRI)-based radiomics model for the noninvasive prediction of tumor–stroma ratio (TSR) in prostate cancer (PCa). Additionally, we sought to explore lesion distribution patterns in the peripheral zone (PZ) and transition zone (TZ) to provide deeper insights into the biological behavior of PCa. Methods: This multicenter retrospective study included 223 pathologically confirmed PCa patients, with 146 for training and 39 for internal validation at Center 1, and 38 for external testing at Center 2. All patients underwent preoperative bpMRI (T2WI, DWI acquired with a b-value of 1400 s/mm², and ADC maps), with TSR histopathologically quantified. Regions of interest (ROIs) were manually segmented on bpMRI images using ITK-SNAP software (version 4.0.1), followed by high-throughput radiomic feature extraction. Redundant features were eliminated via Spearman correlation analysis and least absolute shrinkage and selection operator (LASSO) regression. Five machine learning (ML) classifiers—Logistic Regression (LR), Support Vector Machine (SVM), BernoulliNBBayes, Ridge, and Stochastic Gradient Descent (SGD)—were trained and optimized. Model performance was rigorously evaluated using receiver operating characteristic (ROC) curves and decision curve analysis (DCA). Results: The Ridge demonstrated superior diagnostic performance, achieving AUCs of 0.846, 0.789, and 0.745 in the training, validation, and test cohorts, respectively. Lesion distribution analysis revealed no significant differences between High-TSR and Low-TSR groups (p = 0.867), suggesting that TSR may not be strongly associated with zonal localization. Conclusions: This exploratory study suggests that a bpMRI-based radiomic model holds promise for noninvasive TSR estimation in prostate cancer and may provide complementary insights into tumor aggressiveness beyond conventional pathology. Full article

Background: The high perimandibular approach (HPA) is a feasible surgical technique for open reduction and internal fixation (OR-IF) of mandibular condylar fractures, offering reduced complication rates. In this study, we retrospectively evaluated the treatment outcomes and complications associated with HPA use. Patients and Methods: Patients who underwent OR-IF for mandibular condylar fractures using the HPA at three hospitals in Shimane between June 2019 and March 2024 were included. Data collected included the mechanism of injury, AO classification of the fracture site, fracture type and mode, surgical duration, mouth-opening range at 6 months post-operatively, and peri- and post-operative complications. Results: A total of 42 patients (46 condylar fractures; 18 males and 24 females; mean age, 63.0 years) were included. The fracture pattern included dislocations in 18 cases (42.8%). The mean surgical duration was 75.0 min. Post-operative trismus occurred in 16 patients (38.1%) at 6 months. Longer surgical duration and dislocated fractures were significantly associated with post-operative trismus (p < 0.05). Conclusions: The HPA is safe and effective for managing mandibular condylar fractures. However, post-operative trismus may be influenced by longer surgical duration and fracture types, warranting further investigation and potential post-surgical management. Full article

Background/Objectives: Accurate diagnosis, prognosis, and prediction of treatment response are essential in managing gynecologic cancers and maintaining patient quality of life. Computational pathology, powered by artificial intelligence (AI), offers a transformative opportunity for objective histopathological assessment. This review provides a comprehensive, user-oriented overview of existing AI tools for the characterization of gynecological cancers, critically evaluating their clinical applicability and identifying key challenges for future development. Methods: A systematic literature search was conducted in PubMed and Web of Science for studies published up to 2025. The search focused on AI tools developed for the diagnosis, prognosis, or treatment prediction of gynecologic cancers based on histopathological images. After applying selection criteria, 36 studies were included for in-depth analysis, covering ovarian, uterine, cervical, and other gynecological cancers. Studies on cytopathology and pure tumor detection were excluded. Results: Our analysis identified AI tools addressing critical clinical tasks, including histopathologic subtyping, grading, staging, molecular subtyping, and prediction of therapy response (e.g., to platinum-based chemotherapy or PARP inhibitors). The performance of these tools varied significantly. While some demonstrated high accuracy and promising results in internal validation, many were limited by a lack of external validation, potential biases from training data, and performance that is not yet sufficient for routine clinical use. Direct comparison between studies was often hindered by the use of non-standardized evaluation metrics and evolving disease classifications over the past decade. Conclusions: AI tools for gynecologic cancers represent a promising field with the potential to significantly support pathological practice. However, their current development is heterogeneous, and many tools lack the robustness and validation required for clinical integration. There is a pressing need to invest in the creation of clinically driven, interpretable, and accurate AI tools that are rigorously validated on large, multicenter cohorts. Future efforts should focus on standardizing evaluation metrics and addressing unmet diagnostic needs, such as the molecular subtyping of rare tumors, to ensure these technologies can reliably benefit patient care. Full article

Background: Polyuria–polydipsia syndrome (PPS) in children poses a major diagnostic challenge, as central diabetes insipidus (CDI) and primary polydipsia (PP) require distinct treatments. Although copeptin is a robust diagnostic biomarker, using only fixed thresholds may not adequately support decision making in borderline cases. To address this gap, we evaluated a multimodal diagnostic approach that integrates copeptin dynamics with clinical profiling. Methods: In a prospective diagnostic study (2019–2025), 24 children with PPS (CDI = 11, PP = 13) underwent hypertonic saline testing with serial sodium, osmolality, and copeptin sampling. Predictors included stimulated copeptin, peak sodium, peak osmolality, test duration, and tolerability. A Ridge regression model was applied and internally validated with stratified cross-validation. Results: Stimulated copeptin was the strongest discriminator, while sodium/osmolality dynamics and tolerability provided complementary value. The multimodal model achieved cross-validated AUC of 0.937 with 83.3% accuracy, and the procedure was safe and feasible in children. These findings support moving beyond biomarker cut-offs toward integrative diagnostic approaches that better reflect real-world clinical practice. Conclusions: Combining copeptin with clinical profiling in a penalized regression framework yields a robust and interpretable tool for distinguishing CDI from PP. More broadly, such integrative models may enhance diagnostic precision in rare pediatric disorders and provide a foundation for future multicenter validation and clinical decision-support applications. Full article

Background/Objectives: Non-variceal upper gastrointestinal bleeding (NVUGIB) is associated with considerable morbidity and mortality, particularly in emergency department (ED) settings. While traditional clinical scores such as the Glasgow-Blatchford Score (GBS), AIMS65, and Pre-Endoscopic Rockall are widely used for risk stratification, their accuracy in mortality prediction is limited. This study aimed to evaluate the performance of multiple supervised machine learning (ML) models in predicting 30-day all-cause mortality in NVUGIB and to compare these models with established risk scores. Methods: A retrospective cohort study was conducted on 1233 adult patients with NVUGIB who presented to the ED of a tertiary center between January 2022 and January 2025. Clinical and laboratory data were extracted from electronic records. Seven supervised ML algorithms—logistic regression, ridge regression, support vector machine, random forest, extreme gradient boosting (XGBoost), naïve Bayes, and artificial neural networks—were trained using six feature selection techniques generating 42 distinct models. Performance was assessed using AUROC, F1-score, sensitivity, specificity, and calibration metrics. Traditional scores (GBS, AIMS65, Rockall) were evaluated in parallel. Results: Among the cohort, 96 patients (7.8%) died within 30 days. The best-performing ML model (XGBoost with univariate feature selection) achieved an AUROC > 0.80 and F1-score of 0.909, significantly outperforming all traditional scores (highest AUROC: Rockall, 0.743; p < 0.001). ML models demonstrated higher sensitivity and specificity, with improved calibration. Key predictors consistently included age, comorbidities, hemodynamic parameters, and laboratory markers. The best-performing ML models demonstrated very high apparent AUROC values (up to 0.999 in internal analysis), substantially exceeding conventional scores. These results should be interpreted as apparent performance estimates, likely optimistic in the absence of external validation. Conclusions: While machine-learning models showed markedly higher apparent discrimination than conventional scores, these findings are based on a single-center retrospective dataset and require external multicenter validation before clinical implementation. Full article

Background/Objectives: This study aims to evaluate the functional characteristics of the temporomandibular joint (TMJ) in patients diagnosed with juvenile idiopathic arthritis (JIA). Specifically, it seeks to determine the prevalence of TMJ involvement and its impact on clinical symptoms and functional limitations. Methods: A total of 40 patients diagnosed with JIA according to the International League of Associations for Rheumatology criteria were included. Exclusion criteria encompassed systemic diseases unrelated to JIA, prior craniofacial surgery, and trauma. Participants were divided into two groups: those with TMJ arthritis (n = 23) and those without (n = 17). Clinical assessments were conducted using the Helkimo anamnestic index (Ai) and dysfunction index (Di) to evaluate TMJ-related symptoms. Results: The Ai revealed that most patients reported no or only mild subjective symptoms. Overall Di distributions did not differ significantly between groups, although mandibular mobility was more impaired in the TMJ arthritis group. A moderate correlation (r = 0.4) was observed between Ai and Di. Conclusions: This pilot study indicates that impaired mandibular mobility may suggest TMJ involvement in JIA. Given the study’s limitations, such as being a single-center study with a small sample size and using a CBCT-based classification, further multicenter studies utilizing validated pediatric protocols are necessary to reinforce these preliminary findings. Full article

Background and Objectives: While transurethral resection of the prostate remains the gold standard for surgical treatment of benign prostatic hyperplasia, anatomical endoscopic enucleation of the prostate provides a safe, durable, and size-independent alternative. Our study introduces a specific technical innovation, i.e., en bloc bipolar prostate enucleation performed exclusively via sheath-tip mechanical dissection without the use of a dedicated enucleation loop, combined with the mushroom technique and early apical release. Materials and Methods: Between January 2018 and May 2023, 252 patients with prostate volumes > 30 mL and significant lower urinary tract symptoms underwent en bloc bipolar prostate enucleation via the mushroom technique with early apical release. Data were retrospectively evaluated to assess perioperative results, postoperative outcomes, and complications. Results: The median age of the cohort was 70 (65–76) years, with a median prostate volume of 60 (40–88.5) mL. The median operative time was 40 (30–70) min, and the median weight of enucleated tissue was 34 (16.5–60) g. Significant improvements were observed in the International Prostate Symptom score, Quality of Life score, maximum flow rate, average flow rate, and postvoid residual urine at 12 months (p < 0.001). The rate of transient stress urinary incontinence decreased from 19.44% at 1 month to 2.38% at 12 months. Conclusions: En bloc bipolar prostate enucleation using the mushroom technique is a safe and effective treatment for benign prostatic hyperplasia, yielding significant improvements in urinary symptoms and flow rates, with a manageable complication profile. Further multicenter studies are needed to confirm these findings. Full article

Background: Hepatopancreatobiliary (HPB) surgery is among the most complex domains in oncologic care, where decisions entail significant risk–benefit considerations. Artificial intelligence (AI) has emerged as a promising tool for improving individualized decision-making through enhanced risk stratification, complication prediction, and survival modeling. However, its role in HPB oncologic surgery has not been comprehensively assessed. Methods: This systematic review was conducted in accordance with PRISMA guidelines and registered with PROSPERO ID: CRD420251114173. A comprehensive search across six databases was performed through 30 May 2025. Eligible studies evaluated AI applications in risk–benefit assessment in HPB cancer surgery. Inclusion criteria encompassed peer-reviewed, English-language studies involving human s ubjects. Two independent reviewers conducted study selection, data extraction, and quality appraisal. Results: Thirteen studies published between 2020 and 2024 met the inclusion criteria. Most studies employed retrospective designs with sample sizes ranging from small institutional cohorts to large national databases. AI models were developed for cancer risk prediction (n = 9), postoperative complication modeling (n = 4), and survival prediction (n = 3). Common algorithms included Random Forest, XGBoost, Decision Trees, Artificial Neural Networks, and Transformer-based models. While internal performance metrics were generally favorable, external validation was reported in only five studies, and calibration metrics were often lacking. Integration into clinical workflows was described in just two studies. No study addressed cost-effectiveness or patient perspectives. Overall risk of bias was moderate to high, primarily due to retrospective designs and incomplete reporting. Conclusions: AI demonstrates early promise in augmenting risk–benefit assessment for HPB oncologic surgery, particularly in predictive modeling. However, its clinical utility remains limited by methodological weaknesses and a lack of real-world integration. Future research should focus on prospective, multicenter validation, standardized reporting, clinical implementation, cost-effectiveness analysis, and the incorporation of patient-centered outcomes. Full article

Background/Objectives: Lichen Planus Pemphigoides (LPP) represents a rare variant of Oral Lichen Planus in which the typical pemphigoid-associated antibodies, BP180 and BP230, are present. The objectives of this Systematic Review are to analyze the data currently available in the literature on this rare condition, with the aim of laying the groundwork for future investigations and research. Methods: This Systematic Review was registered in the International Prospective Register of Systematic Reviews (PROSPERO) under the registration number CRD420251133018. Subsequently, a search was conducted on PubMed/Medline, Scopus, and Ovid using specific keywords combined with Boolean operators. Articles published up to 2025 were included. The following types of studies were considered eligible: case reports, clinical conferences, clinical studies, clinical trials, controlled clinical trials, letters, multicenter studies, observational studies, randomized controlled trials, and human-based studies. Book chapters, systematic reviews, narrative reviews, in vitro studies, and animal models were excluded. Results: A total of 67 articles were initially identified; following thorough review and exclusion, 20 articles were retained. The patient data extracted from these selected studies were used to construct a table in which patients were categorized according to both qualitative and quantitative variables. The results highlight that LPP is a condition requiring a complex diagnostic process involving both histological examination and serological testing (Immunofluorescence and Enzyme-Linked Immunosorbent Assay—ELISA). Conclusions: Furthermore, with the advent of immunotherapy, an increasingly well-documented new category of drug-induced LPP has emerged, associated with PD-1 and PD-L1 inhibitors. Full article

Background/Objectives: Cardiac implantable electronic device-related infective endocarditis (CIED-RIE) is a serious condition with significant morbidity and mortality. Although recent advances in imaging and therapeutic approaches have improved management, diagnosing and treating CIED-RIE continues to be challenging. This study aimed to identify factors associated with mortality in CIED-RIE patients. Methods: We conducted a retrospective, multicenter international study of adult patients diagnosed with CIED-RIE between January 2014 and June 2024. Data on demographics, clinical presentation, microbiological findings, imaging results, treatment modalities, and outcomes were collected and analyzed to determine predictors of short-term mortality. Results: A total of 197 patients (mean age: 65.3 ± 14.4 years; 75.1% male) were included. The most common device type was permanent pacemaker (48.2%). Staphylococcus species were the predominant pathogens (62.4%). Surgical intervention was performed in 67.5% of patients, and 90-day mortality occurred in 19.3%. Multivariable analysis identified higher Charlson comorbidity index (HR: 1.31), tricuspid valve involvement (HR: 2.35), vegetation size ≥ 10 mm (HR: 2.53), pulmonary embolism (HR: 3.92), and absence of surgical intervention (HR: 2.90) as independent predictors of increased 90-day mortality. Conclusions: Early identification of high-risk patients and prompt multidisciplinary management, including surgical intervention when indicated, are critical to improving outcomes in patients with CIED-RIE. Full article

Background: Classical Hodgkin lymphoma (cHL) demonstrates high survival rates with the ABVD regimen (doxorubicin, bleomycin, vinblastine, dacarbazine); however, the use of bleomycin is associated with a significant risk of pulmonary toxicity. The Risk-Adapted Treatment of HL (RATHL) trial demonstrated that omitting bleomycin in patients with favorable interim Positron Emission Tomography (PET-CT) results did not adversely affect survival outcomes. In this study, we present real-world data from advanced-stage HL patients treated according to the RATHL protocol. Methods: This multicenter, retrospective study included newly diagnosed cHL patients with Ann Arbor stage IIB–IV disease or stage IIA disease with bulky disease or with involvement of three or more sites, enrolled from 29 centers across Türkiye. The analysis focused on patients whose initial treatment was de-escalated from ABVD to AVD (bleomycin was omitted). Data were collected on demographic and clinical prognostic characteristics, interim PET-CT findings (evaluated using the Deauville score), progression-free survival (PFS) and overall survival (OS). Survival outcomes were assessed using Kaplan–Meier analysis. Results: A total of 379 patients were included, with a median age of 34 years (range: 18–78). Following interim PET-CT assessments (After 2 cycles of ABVD), Deauville scores were 1 in 39.8% of patients, 2 in 39.1%, and 3 in 21.1%. Based on these results, bleomycin was omitted immediately after interim PET-CT in 73.9% of patients, after one additional ABVD cycle in 12.1%, and after two additional cycles in 14%. The median follow-up duration was 28 months (range: 6–96). The 3-year PFS and OS rates were 86.0% and 96.1%, respectively. Patients with Deauville scores of 1–2 had a 3-year PFS rate of 87.6%, compared to 79.8% in those with a score of 3 (p = 0.087). Increased age, poor Eastern Cooperative Oncology Group Scale (ECOG) performance status, bulky disease, and higher International Prognostic Scores (IPS) were significantly associated with inferior OS (p < 0.05). There were no significant differences in OS among patients who received 2, 3, or 4 cycles of ABVD. However, among patients treated with 2 cycles of ABVD, both extranodal involvement (p = 0.039) and higher IPS (p = 0.002) were significantly associated with decreased PFS. Conclusions: Our findings demonstrate that PET-guided de-escalation of bleomycin after two cycles of ABVD is feasible, effective, and safe in real-world multicenter practice in Türkiye. The survival outcomes are comparable to those reported in the RATHL study, reinforcing the role of interim PET-CT in guiding individualized therapy. However, patients with high IPS or extranodal involvement may require more tailored management strategies. Full article