Search Results (60,088)

Background/Objectives: Thymomas are the most common tumors of the anterior mediastinum. While early-stage disease often has a favorable prognosis, therapeutic options in advanced stages remain limited. Moreover, the molecular profile of thymomas is still poorly characterized. In the present study, we explored the presence of targetable mutations and programmed death-ligand 1 (PD-L1) expression in a cohort of surgically resected thymomas. Furthermore, we investigated the correlation between PD-L1 expression, histological subtype, and risk of recurrence in patients who underwent curative-intent thymectomy. Methods: Mutational profiling was performed using a DNA-based NGS Cancer Panel of 16 genes. PD-L1 expression was evaluated via Tumor Proportion Score (TPS), and thymomas with TPS ≥ 50% were identified as high expressors. The associations with histological subtype and disease-free survival (DFS) were analyzed using logistic regression, Cox proportional hazards models, and Kaplan–Meier survival curves. Results: In our study, 2/37 (5.4%) of tested neoplasms (type AB and B2 thymoma) reported as a PIK3CA mutation; no other targetable mutations were observed. Moreover, high PD-L1 expression (≥50%) was reported in (15/37) 40.5% of patients and was significantly associated with aggressive histological subtypes (B2 and B3) (p < 0.001). Logistic regression analysis showed that high PD-L1 expression was a significant predictor of aggressive histology (McFadden’s R² = 0.268, p < 0.001), with an odds ratio of 15.5 (95% CI: 2.9–83.4; p = 0.001). During follow-up, 5/37 (13.5%) of patients experienced disease recurrence; however, no significant difference in DFS was found between high and low PD-L1 expression groups. Conclusions: Our data confirm the presence of PIK3CA mutations in thymomas and encourage the exploration the potential role of molecular target therapy in this setting. Moreover, we underlined that high PD-L1 expression level is associated with more aggressive thymoma subtypes and may have a role as a prognostic biomarker. These findings support the need for further studies on the potential role of molecular and predictive pathology in thymic epithelial tumors. Full article

Stroke frequently results in persistent upper limb impairments, which are often accompanied by compensatory movement strategies that are not fully captured by conventional clinical assessment scales. Quantitative kinematic analyses may provide more objective and sensitive measures of motor dysfunction. In this study, we propose a probabilistic, distribution-based analysis of upper limb kinematics to quantify motor disability in post-stroke patients. We analyzed reaching movement data acquired with a markerless Kinect V2 system from 36 post-stroke patients and age-matched healthy controls. Wrist velocity profiles were characterized using distribution metrics, including variance, skewness, kurtosis, and entropy, and divergence measures (Hellinger distance, Kullback–Leibler divergence, and Jensen–Shannon divergence). Group differences between patients and controls, as well as across impairment levels stratified by the Fugl-Meyer (FM) score, were evaluated. Several distribution metrics significantly discriminated patients from controls and scaled with motor impairment severity. In particular, divergence-based measures showed a strong association with FM scores, indicating increasing deviation from normative movement patterns with greater impairment. These findings demonstrate that distribution-based metrics focusing on kinematic analysis provide a clinically meaningful, objective descriptor of motor dysfunction and complement conventional biomechanical assessments, offering a sensitive framework for quantifying motor disability after stroke. Full article

Background and Objectives: Vaginal vault prolapse is a known complication following anterior pelvic exenteration in women undergoing radical cystectomy. The aim of this study is to evaluate the feasibility, safety, and early outcomes of a novel anatomical approach for preventing vaginal vault prolapse after radical cystectomy. This study introduces a standardized laparoscopic technique that utilizes round ligament preservation and fixation to provide anatomical support to the vaginal apex. Materials and Methods: This study is a retrospective analysis of prospectively collected data from a single center, including thirteen female patients with uterus and adnexa in situ who underwent laparoscopic radical cystectomy with bilateral round ligament fixation to the vaginal cuff. The round ligaments were mobilized and sutured without tension. Vaginal closure was performed with barbed sutures. Results: No intraoperative complications occurred. At a median follow-up of 18.2 months, no cases of vaginal vault prolapse or dehiscence were observed. One patient experienced transient pelvic discomfort. Conclusions: This is the first report of a standardized mesh-free approach for vaginal apex support during laparoscopic anterior exenteration. The technique is feasible, safe, and may reduce postoperative prolapse risk. Full article

Background/Objectives: While most patients resume sports within one year after total knee arthroplasty (TKA), data on whether patients achieve their desired level of sports activity remain limited. This study aimed to evaluate the relationship between desired sports activity levels and postoperative outcomes after TKA and to identify factors associated with achieving the desired activity level. Methods: This retrospective cohort study included 280 patients (63.9% female; mean age, 65.7 years) who underwent primary TKA with a mean follow-up of 28.2 months. The University of California and Los Angeles (UCLA) activity score was used pre- and postoperatively to assess the desired and the achieved activity level. Results: The mean UCLA activity score improved significantly after surgery (from 4.6 to 5.6; p < 0.001). However, the mean preoperative desired UCLA score was significantly higher than the mean postoperative achieved UCLA score (7.1 vs. 5.6; p < 0.001). Overall, 34.6% of patients reached their desired activity level. These patients demonstrated a significantly lower preoperative desired UCLA score (6.1 vs. 7.6; p < 0.001) and a higher postoperative achieved UCLA score (6.7 vs. 5.0; p < 0.001) compared with patients who did not. Male sex, higher preoperative UCLA scores, and lower preoperative desired UCLA scores were identified as independent predictors of achieving the desired activity level. Conclusions: The present study demonstrated that despite excellent Knee Society function and WOMAC scores only 1/3 of patients reach their sport-related desired activity level. Surgeons must ensure that they communicate realistic expectations to patients prior to surgery, in order to avoid dissatisfaction that may arise from unmet expectations. Full article

Morbid obesity is a complex, multifactorial disorder characterized by metabolic and inflammatory dysregulation. The aim of this study was to observe changes in obese patients adhering to a personalized nutrition plan based on multi-omic data. This study included 14 adult patients with a body mass index (BMI) > 40 kg/m² who were consecutively recruited from those presenting to our outpatient clinic and who met the inclusion criteria. Clinical, biochemical, hormonal, and glycomic parameters were assessed, along with whole-genome sequencing (WGS) that included a focused analysis of obesity-associated genes and an extended analysis encompassing genes related to cardiometabolic disorders, hereditary cancer risk, and nutrigenetic profiles. Patients were stratified into nutrigenetic clusters using a patented unsupervised machine learning platform (German Patent Office, No. DE 20 2025 101 197 U1), which was employed to generate personalized nutrigenetic dietary recommendations for patients with morbid obesity to follow over a six-month period. At baseline, participants exhibited elevated glucose, insulin, homeostatic model assessment for insulin resistance (HOMA-IR), triglycerides, and C-reactive protein (CRP) levels, consistent with insulin resistance and chronic low-grade inflammation. The majority of participants harbored risk alleles within the fat mass and obesity-associated gene (FTO) and the interleukin-6 gene (IL-6), together with multiple additional significant variants identified across more than 40 genes implicated in metabolic regulation and nutritional status. Using an AI-driven clustering model, these genetic polymorphisms delineated a uniform cluster of patients with morbid obesity. The mean GlycanAge index (56 ± 12.45 years) substantially exceeded chronological age (32 ± 9.62 years), indicating accelerated biological aging. Following a six-month personalized nutrigenetic dietary intervention, significant reductions were observed in both BMI (from 52.09 ± 7.41 to 34.6 ± 9.06 kg/m², p < 0.01) and GlycanAge index (from 56 ± 12.45 to 48 ± 14.83 years, p < 0.01). Morbid obesity is characterized by a pro-inflammatory and metabolically adverse molecular signature reflected in accelerated glycomic aging. Personalized nutrigenetic dietary interventions, derived from AI-driven analysis of whole-genome sequencing (WGS) data, effectively reduced both BMI and biological age markers, supporting integrative multi-omics and machine learning approaches as promising tools in precision-based obesity management. Full article

Background: The retinal changes caused by ethambutol are not clear in patients with the administration of ethambutol and without ethambutol-induced optic neuropathy (EON). The aim of this systematic review is to estimate the changes in retinal nerve fiber layer (RNFL) and ganglion cell layer and inner plexiform layer (GCIPL) thicknesses measured by optical coherence tomography (OCT) in patients with mycobacterial infection treated with ethambutol and not suffering from EON. Methods: A systematic review of articles was conducted by searching PubMed, Embase, and Web of Science until November 2025. Additional studies were identified by the review of references. Search terms included OCT and ethambutol. Longitudinal observational studies using an OCT device to measure RNFL and GCIPL thicknesses before and after the administration of ethambutol in patients with mycobacterial infection without ocular diseases were included. The extraction of data in studies was performed by two researchers using data extraction sheets. The meta-analysis was conducted using the random-effect model. Results: In total, 14 studies (n = 1138) were eligible for the systematic review. Meta-analysis combining RNFL measured after the longest duration of ethambutol administration showed no significant decrease compared to RNFL before treatment. However, there were significant decreases in RNFL thickness in male-dominant studies, studies conducted in Turkey and India, and studies conducted by the Cirrus OCT device. In addition, the decreases in RNFL thickness were correlated with the duration of ethambutol administration in male-dominant studies. Only two studies reported the thickness changes in GCIPL, and the study with a higher male proportion showed significant decreases in GCIPL thickness. Conclusions: Ethambutol does not cause a significant RNFL decrease generally in mycobacterial infection patients; however, it may lead to decreased RNFL thickness in male patients and patients in some regions, even though they do not suffer from EON. Full article

The poor clinical outcomes of pediatric high-grade glioma (pHGG) highlight the urgent need for new therapies. Oligodendrocyte lineage transcription factor 2 (OLIG2) is a pro-mitotic transcription factor highly expressed in glioma stem cells and may represent a novel therapeutic target. To evaluate the therapeutic efficacy of an OLIG2 inhibitor CT-179 in pHGG, we determined the OLIG2 mRNA expression in 10 patient-derived orthotopic xenograft (PDOX) models. In vitro activities of CT-179 were analyzed in monolayer and neurosphere cells (0–10 µM) with and without radiation (XRT) (0–8 Gy), brain penetration was evaluated in tumor-bearing PDOX mice, and in vivo efficacy was determined at 15–240 mg/kg (oral) alone or combined with XRT (2 Gy/day × 5 days). Changes in animal survival times were analyzed using the Kaplan–Meier method, followed by pair-wise comparisons. Increased OLIG2 mRNA expression was detected in seven out of ten PDOX models. CT-179 inhibited cell viability in a time- and dose-dependent manner in all eight pGBM xenograft tumors (IC₅₀ 0.03–10 µM) and was potentiated by XRT (0.03–1 µM). Oral gavage (24 mg/kg) of CT-179 for 5 days led to effective penetration in mouse cerebrum (3232.7 ± 569.2 ng/g), cerebellum (1563.3 ± 269.6 ng/g), brain stem (1685.3 ± 309 ng/g), and PDOX tumors (1814 ± 110.3 ng/g) vs. 361.3 ± 1.5 ng/mL in serum. CT-179 alone was not active at 200 mg/kg in four models, although it was moderately effective at 240 mg/kg in one model. When combined with XRT, a significant extension of animal survival times was observed in two out of four models. Doses needed to eliminate OLIG2 expression in vitro varied from 0.3 to >1 µM in pGBM cells. In summary, our data showed that orally administered CT-179 penetrated the blood–brain barrier (BBB) and exhibited potential for inhibiting pGBM growth when combined with XRT. Full article

Background/Objectives: Obstructive Sleep Apnea Syndrome (OSAS) is a chronic disorder characterized by repeated upper airway obstruction during sleep, leading to intermittent hypoxia and elevated sympathetic activity. OSAS is strongly linked to cardiovascular comorbidities such as hypertension, arrhythmias, heart failure, and atherosclerosis, contributing to structural and functional cardiac alterations. Methods: This study enrolled 105 consecutive patients diagnosed with OSAS and a control group of 100 patients without the syndrome. All participants underwent a comprehensive echocardiographic evaluation using Doppler imaging to assess cardiac structure and function. Results: Hypertension was significantly more prevalent in the OSAS group (81%) compared to controls (74%). Left ventricular diastolic dysfunction occurred in 56.2% of OSAS patients versus 26% of controls. Left atrial enlargement and left ventricular hypertrophy were also more frequent in the OSAS group (21% and 51.4%, respectively) compared to controls (13% and 5%). Permanent atrial fibrillation was present in 17.1% of OSAS patients, significantly higher than the 7% observed in controls. These findings highlight the pronounced cardiac remodeling and arrhythmic burden associated with OSAS. Conclusions: The data confirm that OSAS is associated with increased cardiovascular abnormalities detectable by echocardiography, underscoring the need for routine cardiovascular screening in OSAS patients. Given the systemic implications of OSAS beyond sleep disturbances, a multidisciplinary approach is essential for early diagnosis and optimized management, aiming to mitigate cardiovascular risk and improve outcomes. OSAS is a significant cardiovascular risk factor requiring comprehensive clinical attention. Full article

Purpose: Recently, authors have shown increasing interest in the emerging HER2-low subtype in breast cancer. These tumors are currently classified and treated as HER2-negative tumors. Neoadjuvant endocrine therapy (NET) has been used to achieve tumor downstaging and assess treatment response in postmenopausal women with low-grade luminal HER2-negative tumors. This study aimed to determine whether the response to NET was affected by low levels of HER2 expression in luminal tumors. Methods: The study was a single-centered retrospective investigation. Data were gathered from the medical records of patients from 2017 to 2023. All patients had luminal HER2-negative tumors and were treated with NET and subsequent surgery. Results: In total, 175 tumors were analyzed; 24.0% of the tumors were HER2-zero, 48.0% were HER2-low 1+, and 28.0% were HER2-low 2+. No significant differences were found when assessing NET response between the three groups, nor when evaluating tumor features. Response to NET was influenced by estrogen receptor levels, histological subtype and histological grade at diagnosis, Ki67 levels at interim biopsy, and NET duration. No differences were found for progression-free survival (PFS) or overall survival (OS) between HER2 groups. The group with Ki67 ≤ 10% at interim biopsy had longer PFS than the Ki67 > 10% group (p < 0.05). No differences for OS were found between these groups. Conclusions: Response to NET was not influenced by low levels of HER2 expression in luminal tumors when compared to HER2-zero tumors. PFS was longer for patients who had lower Ki67 levels at interim biopsy after NET. Full article

Background: Clinical Ethics Consultation (CEC) helps healthcare professionals, patients, and families address ethically complex situations in clinical practice. Since 2016, requests for CEC at the Fondazione Policlinico Universitario “A. Gemelli” IRCCS (FPG) have been entered into the hospital IT system like other consulting services. This has increased both the number of requests and the need to monitor and evaluate the service. Aims: This qualitative study investigates how the CEC service at FPG is perceived in terms of its value, role, and impact, and further aims to identify appropriate strategies for evaluating the service. Methods: Semi-structured interviews were conducted with 28 healthcare professionals who had used or taken part in the service within the previous two years. Data were examined using reflective thematic analysis, leading to the development of codes and themes. Results: Five main themes emerged: (1) Role and identity of the clinical ethics consultant the, (2) Benefits of CEC for clinical practice, (3) How to evaluate the CEC Service, (4) HCPs’ Evaluation, and (5) CEC Service Improvement Strategies. Participants saw the consultant as an “active third party” who combines ethical, clinical, and communication skills to mediate conflicts, support teamwork, and guide shared care planning. The service was viewed as strengthening patient-centered care by improving communication with patients and families, clarifying treatment proportionality, and reducing clinicians’ decisional isolation. Interviewees emphasized the need for structured evaluation tools that include both quantitative indicators and qualitative feedback. Satisfaction with the service was consistently high, with recommendations to expand consultant availability, improve timeliness, and enhance training. Conclusions: CEC appears to serve as a clinical, relational, and training resource that fosters ethically grounded, collaborative, and person-centered care. Full article

Background/Objectives: To evaluate the clinical and MRI characteristics of benign solitary schwannomas of the extremities, compare pre- and postoperative neurological symptoms, and identify preoperative and intraoperative risk factors for postoperative complications. Methods: A retrospective review was conducted on 47 patients with histopathologically confirmed benign solitary schwannomas of the extremities who underwent surgical excision. Demographic data, MRI characteristics (tumor volume, perilesional edema, and degenerative changes such as cystic components or intratumoral hemorrhage), fascicular relationship, and use of tru-cut biopsy were recorded. Pre- and postoperative neurological symptoms were compared. Univariate logistic regression analysis was performed to identify factors associated with postoperative complications. Results: The mean age was 38.6 ± 15 years, and the mean follow-up period was 109.8 ± 65.1 months. Lesions were predominantly located in the upper extremity (65.9%), with a mean volume of 9.6 ± 4.8 cm³; perilesional edema and/or degenerative changes were present in 53.1% of cases. Postoperative complications occurred in 19.1% of patients, with intrafascicular involvement being a significant predictor (OR = 5.4, p = 0.037) and a positive preoperative Tinel’s sign showing a trend toward significance (OR = 4.2, p = 0.084). Tumor volume, perilesional edema, degenerative changes, tru-cut biopsy, and anatomical location were not significantly associated with complications. At final follow-up, pain remission was 82.1%, and paresthesia improvement was 63.6%. Conclusions: Intrafascicular involvement was associated with postoperative complications in univariate analysis, whereas preoperative MRI characteristics, biopsy, and Tinel’s sign showed no predictive value for postoperative risk. Full article

This study introduces a hybrid methodological approach for personalised clinical decision support, integrating SHACL-based deterministic constraints with Bayesian probabilistic models. The primary goal is to validate the model and demonstrate the benefits of combining encoded clinical knowledge with probabilistic uncertainties in managing complex therapeutic scenarios. The framework was applied to recurrent urinary tract infections (UTIs) in postmenopausal patients, a clinical context marked by high frequency, treatment challenges, and potential conflicts among therapeutic guidelines. Realistic simulated case studies were developed, encompassing both simple clinical profiles and complex situations, such as patients with antibiotic resistance. Each profile was modelled in RDF/Turtle, enabling semantic representation of clinical features and therapeutic rules. The system automatically calculates success and failure probabilities for different therapeutic scenarios, dynamically adapting them based on follow-up data. This allows clinicians to assess not only the initial therapy choice (Case study no. 1) but also the potential addition of supplementary interventions during treatment (Case study no. 2). Results highlight that the proposed hybrid SHACL–Bayesian framework enables tightly coupled deterministic–probabilistic reasoning, where SHACL constraints define the admissible clinical decisions and Bayesian inference operates within this validated space. Compared to deterministic or probabilistic approaches, the combined framework more effectively handles uncertainty, guideline conflicts, and temporal updates. The scientific contribution lies in showing that this integration enhances decision support for recurrent UTIs in postmenopausal patients, providing clinically consistent, transparent, and adaptive therapeutic recommendations aligned with the patient’s evolving condition. Full article

Reoperation for papillary thyroid carcinoma (PTC) requires precise lymph node metastasis assessment, yet ultrasound (US) alone may be insufficient in complex or high-risk cases. This study evaluated whether supplementing US with magnetic resonance imaging (MRI) improves surgical guidance and outcomes in reoperation. We retrospectively analyzed 375 patients who underwent reoperation between 2014 and 2022. Propensity score matching yielded 101 patients in the USUS-only group and 62 in the US+MRI group. Pathological and imaging data were compared to assess diagnostic performance, surgical outcomes, biochemical responses, and recurrence-free survival. The combined approach significantly increased sensitivity for detecting central lymph node metastasis from 52.5% to 90.9% and resulted in higher rates of central neck dissections (65.1% versus 45.5%) with greater lymph node yield (median: 29 versus 20) but lower lymph node ratios. More patients in the combined group achieved excellent biochemical responses (50.0% versus 27.7%). While overall recurrence-free survival (RFS) was not significantly different, the US+MRI group showed improved RFS among patients with ≥2 positive central nodes (HR = 0.24, p = 0.032). Importantly, complication rates were comparable, suggesting that improved outcomes were achieved without added surgical risk. Combined US and MRI assessment enhances diagnostic performance and may improve surgical and oncological outcomes in select high-risk patients undergoing PTC reoperation. Full article

Background: Pituitary neuroendocrine tumors (PitNETs) are a core manifestation of multiple endocrine neoplasia type 1 (MEN1), yet their true prevalence, biological behavior, and optimal management remain debated. Earlier reports suggested increased aggressiveness compared with sporadic PitNETs, while more recent surveillance-based studies indicate a predominantly indolent phenotype. Methods: We conducted a retrospective single-center study including all patients with clinical, familial, or genetic MEN1 referred to the Endocrinology Unit of the University of Naples “Federico II”, ENETS Center of Excellence, between January 2004 and June 2025. Demographic, clinical, radiological, hormonal, and therapeutic data were systematically collected. PitNETs were classified by size and hormonal activity. Results: Among 103 MEN1 patients (61 women), 50 (48.5%) were diagnosed with PitNETs at a mean age of 35.1 years. Microadenomas predominated (60%), and tumors were equally distributed between functioning and non-functioning lesions. Prolactin-secreting PitNETs were the most common functioning subtype (42%), followed by rare GH-, ACTH-, or mixed-secreting PitNETs. Dopamine agonists, mainly cabergoline, were prescribed in 38% of cases, while neurosurgical intervention was required in 14%, exclusively for macroadenomas. During follow-up, recurrence occurred in 8% of patients. No significant sex-related differences were observed in prevalence, tumor size, functional status, treatment approach, or outcomes. Conclusions: In our MEN1 cohort, PitNETs were frequent but largely indolent, with a predominance of microadenomas and limited need for surgery. Our findings support individualized, subtype-driven surveillance strategies, with conservative management for clinically non-functioning microadenomas and closer monitoring of prolactin-secreting PitNETs due to variable medical responsiveness. Full article

Background/Objectives: The foetal alcohol syndrome spectrum is linked with neurodevelopmental delay and cognitive and educational problems. Direct consequences of prenatal alcohol exposure include impaired processes of neural migration and brain development. Among the important features present in affected children are impaired communicational skills and intelligence. Methods: Here we presented the case–control comparison of 124 children with foetal alcohol syndrome spectrum disorder (FAS: 62 (50%), pFAS: 34 (27.42%) and ARND: 28 (22.58%)) and 53 healthy controls regarding intelligence quotient and a verbal fluency task. The verbal and non-verbal intelligence was measured using the WISC-R scale, and the verbal fluency task encompassed phonemic, semantic and categorial assessment in 15 and 60 s; we used the authors’ parental/caregiver survey to determine risk factors. In statistical analysis both methods of classical parametric/non-parametric tests and machine learning algorithms were used. Results: Foetal alcohol syndrome spectrum patients were clearly distinguished from healthy controls regarding total verbal and non-verbal intelligence, as well as all three categories of verbal fluency (p < 0.01). ML methods distinguished an FAS group with 0.49 precision and 80% recall and for pFAS and ARND diagnoses we obtained: 0.50/0.33 precision and 3%/7% recall. None of the parameters analysed in our study differentiated foetal alcohol syndrome, partial foetal alcohol syndrome and alcohol-related neurodevelopmental disorders. Conclusions: Children with foetal alcohol syndrome spectrum disorder markedly differ from healthy control subjects in intelligence and verbal fluency. The diagnostic sub-types of foetal alcohol spectrum are not clearly defined in obtained neuropsychological and clinical data. Full article