Medical sciences (Basel, Switzerland)最新文献

Background: Renal Cell Carcinoma (RCC) is the most common type of kidney cancer and requires accurate histopathological grading for effective prognosis and treatment planning. However, manual grading is time-consuming, subjective, and susceptible to inter-observer variability. Objective: This study proposes EAT-Net (Efficient Attention Transformer Network), a dual-stream deep learning model designed to automate and enhance RCC grade classification from histopathological images. Method: EAT-Net integrates EfficientNetB0 for local feature extraction and a Vision Transformer (ViT) stream for capturing global contextual dependencies. The architecture incorporates Squeeze-and-Excitation (SE) modules to recalibrate feature maps, improving focus on informative regions. The model was trained and evaluated on two publicly available datasets, KMC-RENAL and RCCG-Net. Standard preprocessing was applied, and the model's performance was assessed using accuracy, precision, recall, and F1-score. Results: EAT-Net achieved superior results compared to state-of-the-art models, with an accuracy of 92.25%, precision of 92.15%, recall of 92.12%, and F1-score of 92.25%. Ablation studies demonstrated the complementary value of the EfficientNet and ViT streams. Additionally, Grad-CAM visualizations confirmed that the model focuses on diagnostically relevant areas, supporting its interpretability and clinical relevance. Conclusion: EAT-Net offers an accurate, and explainable framework for RCC grading. Its lightweight architecture and high performance make it well-suited for clinical deployment in digital pathology workflows.

Background/Objectives: Suprascapular nerve block (SSNB) is a useful therapeutic option for chronic shoulder pain, although the synergistic use of corticosteroids with anesthetics to prolong its effect is a controversial topic. The primary objective of this study was to compare the evolution of pain and functionality using the visual analog scale (VAS) and the Disabilities of the Arm, Shoulder and Hand (DASH) questionnaire between patients treated with SSNB with corticosteroids (cSSNB) and without them (sSSNB). Methods: A retrospective, observational, longitudinal, analytical cohort study was conducted in 28 patients (14 n per group) aged 50-80 years who had undergone SSNB with 4 mL of 0.25% bupivacaine and 40 mg/mL triamcinolone during 2024 for chronic shoulder pain lasting more than 6 months. The variables to be collected were VAS, DASH, range of motion (ROM) and Lattinen Index (LI) at baseline, the first and the third month. Patients were grouped according to the type of SSNB (cSSNB vs. sSSNB) and analyzed longitudinally and cross-sectionally using IBM-SPSS Statistics version 28.0.0. Results: Regarding pain, the cSSNB obtained a significant reduction in the median VAS of 4 points in the first month (p = 0.001) and in the third month (p = 0.002). In addition, significantly lower evaluations in VAS were obtained in the third month of 3 points (p = 0.04) in favor of the cSSNB. Regarding functionality, a reduction in evaluations with respect to the initial DASH were observed only in the cSSNB, with a difference in the first month of 21.80 points (p = 0.001) and 21.35 points (p = 0.003) in the third month. In addition, differences between groups were found, in favor of the cSSNB, of 19.20 points (p = 0.017) in the first month and 12.55 points (p = 0.012) in the third month. Conclusions: The combined use of corticosteroids in SSNB appears to be associated with better short-to medium-term outcomes in terms of pain and function, compared to the use of SSNB without corticosteroids in chronic rotator cuff pathologies.

Background: Frailty is a multidimensional syndrome characterized by reduced physiological reserve and resilience and has become a crucial predictor of outcomes in liver surgery. Unlike chronological age, frailty reflects broader vulnerabilities that significantly influence postoperative recovery.

Aim: To review and synthesize current evidence on the relationship between frailty and postoperative outcomes following liver resection, with an emphasis on short-term complications, mortality, and long-term survival.

Methods: A comprehensive literature review was performed, drawing on recent meta-analyses, large-scale cohort studies, and prospective observational data. Frailty was evaluated using a range of assessment tools, including the Modified Frailty Index (mFI), Clinical Frailty Scale (CFS), Kihon Checklist (KCL), and claims-based measures such as the Johns Hopkins Frailty Indicator.

Results: Across studies, frailty has been consistently linked to a higher incidence of postoperative complications, such as post-hepatectomy liver failure (PHLF), infections, extended hospital stays, and increased mortality. In patients undergoing liver resection for cancer, frailty is also associated with poorer long-term survival. Importantly, frailty serves as an independent risk factor, even after adjusting for age, comorbid conditions, and tumor characteristics. Preoperative identification of frailty enhances risk stratification, informs surgical planning, potentially favoring parenchymal-sparing or minimally invasive approaches, and highlights patients who may benefit from prehabilitation.

Conclusions: Frailty is a strong and independent predictor of poor outcomes after liver resection. Incorporating frailty assessment into routine preoperative evaluation can improve surgical decision-making, facilitate informed patient counseling, and optimize perioperative care strategies.

Human infertility represents a multifaceted condition, with oxidative stress (OS) and microRNAs (miRNAs) emerging as key contributors to its pathophysiology. This comprehensive review explores the complex interplay between reactive oxygen species (ROS) and miRNAs in male and female reproductive dysfunctions. ROS overproduction damages DNA, lipids, and proteins, impairing sperm quality and oocyte maturation. In males, OS is a leading cause of infertility, especially in conditions like varicocele, where key miRNAs such as miR-21, miR-34a, and miR-155 are dysregulated. In females, oxidative imbalance affects granulosa cells and follicular environments in disorders such as PCOS, premature ovarian insufficiency (POI), and endometriosis. Several miRNAs (e.g., miR-132-3p, let-7, miR-642a-5p) regulate mitochondrial function, steroidogenesis, and apoptosis through redox-sensitive signaling pathways (PI3K/Akt, NF-κB, FOXO1). Their altered expression in ovarian and seminal environments correlates with poor reproductive outcomes. Emerging evidence supports their potential role as diagnostic biomarkers and therapeutic targets, although most findings are based on animal models or in vitro studies. This review highlights the therapeutic potential of miRNA modulation and calls for further clinical research to validate miRNA-based interventions. Ultimately, understanding the miRNA-OS nexus offers promising avenues for improving diagnosis, prognosis, and treatment of infertility across both sexes.

Background/Objectives: Cancer characteristics are mainly due to mutations in genes that regulate key pathways. One mechanism for identifying and correcting these mutations is the Mismatch Repair System. Given the lack of data on MMR in breast cancer FFPE samples, this study aims to examine hMSH2 and hMSH6 gene expression in FFPE tumor biopsies. Methods: One hundred patients with breast cancer were included in this study, from which tumor samples were obtained. Expression of the hMSH2 and hMSH6 genes was evaluated by qPCR. Results: Out of 100 tumor samples, 89 were suitable for molecular analysis. Of these, 10 (11.23%) expressed the hMSH2 gene and 4 (4.5%) expressed the hMSH6 gene. No associations were found between hMSH2 and hMSH6 expression and tumor staging, HER2, ER, PR, or Ki-67 expression. Conclusions: Our results suggest that the expression of the proposed markers is decreased in breast tumorigenesis.

Background: Agmatine (AG) is an endogenous neurotransmitter discovered in 1910. It acts on imidazoline I1 and I2 receptors, alpha-2 adrenoceptors, N-methyl-D-aspartate receptors (NMDAR), and serotonergic receptors and modulates nitric oxide synthase (NOS) subtypes. It has neuroprotective, anxiolytic, antidepressant, anticonvulsant, and anti-inflammatory properties and is involved in cognitive functions and withdrawal. The cardiovascular effects of AG began to be explored after the hypotensive effect of clonidine, an imidazoline agonist, was demonstrated. The current study aimed to systematize the effects of AG on the cardiovascular system obtained in previous preclinical studies.

Methods: We searched three databases, PubMed, Cochrane, and Embase, using the keywords "agmatine" and "cardiac" or "vascular."

Results: Sixty studies were eligible and included in the analysis. Initially identified as Clonidine Displacing Substance (CDS), AG has demonstrated dual effects-an increase or decrease in blood pressure or in heart rate.

Conclusions: The effects exerted by AG depend on the dose and route of administration, as well as on the receptors involved and the pathophysiological pathway used.

Background/objectives: The objective of this ten-year report is to describe temporal trends in the cardiovascular health (CVH) score and its individual components across ages and sexes. We also examined the impact of the post-COVID-19 period on ideal CVH and identified demographic predictors of favorable cardiovascular risk profiles.

Methods: Data for this cross-sectional study were collected between 2015 and 2024 as part of the Lookup 8+ project, an ongoing initiative integrating field-based CVH assessments across Italy. CVH was operationalized using a modified CVH score (0-7 points) inspired by Life's Simple 7, combining behavioral and clinical metrics. Trends over time and across demographic groups were examined using descriptive statistics and multivariable models adjusted for age, sex, and year of assessment.

Results: The study included 18,491 participants (mean age 56.1 ± 14.8 years; 55.2% women). After an initial decline in CVH score between 2015 and 2017 (mean score from 4.39 to 3.95), a gradual improvement followed, reaching 4.41 in 2024. Younger adults (18-39 years; 71.9% in 2024) and women (56.8%) consistently showed the highest prevalence of ideal CVH (score ≥ 5). The post-COVID-19 period was independently associated with higher odds of ideal CVH (OR 1.32; 95% CI 1.24-1.40). While blood pressure and cholesterol metrics improved, dietary quality and glycemic control worsened over time.

Conclusions: From 2015 to 2024, overall CVH improved among Lookup participants, particularly among younger individuals after the COVID-19 pandemic. However, substantial age- and sex-related gaps remain, requiring targeted and equity-oriented prevention efforts.

Background/Objectives: Although peritoneal dialysis (PD) practices have improved over the past decades, limited evidence exists on all-cause mortality and cardiovascular death following PD-associated peritonitis. This study aimed to investigate the association between PD-associated peritonitis and the risk of all-cause mortality and cardiovascular death. Methods: This multicenter, retrospective cohort study included adult patients who newly initiated PD between 1 January 2006 and 31 December 2020, with follow-up through 30 September 2022. Patients were matched 1:1 by time from PD initiation to index date (the occurrence date of PD-associated peritonitis for the exposure group and the corresponding matched time on PD for the non-exposure group [individuals without any peritonitis event]), age, and sex. Multivariable Cox proportional hazards models with shared frailty correction and competing risk models were used to estimate hazard ratio (HR) and subdistribution hazard ratio (SHR), respectively. Subgroup analyses were conducted by age, sex, PD modality, and comorbid conditions. Results: The cohort included 1510 matched pairs (total sample, 3020; mean age [SD], 58.6 [14.2] years; 1618 males [53.6%]), with a median follow-up of 5.6 years. After adjusting for sociodemographic, PD, and clinical characteristics and laboratory profiles, patients with any PD-associated peritonitis episode had significantly higher risk of all-cause mortality (HR, 2.17 [1.78-2.66], p < 0.001; SHR, 2.00 [1.74-2.29], p < 0.001) and cardiovascular death (HR, 2.90 [2.05-4.59], p < 0.001; SHR, 2.25 [1.66-3.05], p < 0.001) compared to those without PD-associated peritonitis. Subgroup analyses revealed no significant interactions (all p values for interaction > 0.05). Conclusions: PD-associated peritonitis was independently associated with substantially increased risk of all-cause and cardiovascular mortality among patients undergoing PD. These findings support the need for targeted interventions and clinical strategies aimed at reducing adverse outcomes following PD-associated peritonitis.

Background: Sodium/iodide symporter (NIS) is a membrane protein involved in iodide transport into cells, making it a key component of thyroid physiology and radioiodine therapy for thyroid cancer. Although NIS is expressed in many extrathyroidal tissues, including breast tumors, its functional role and prognostic significance in these contexts remain a subject of active investigation. Understanding the mechanisms regulating NIS, its influence on cellular processes such as migration and metastasis, and its connection with transcription factors like FOXA1 could contribute to the development of new therapeutic strategies for breast cancer treatment. This study aims to investigate the correlation between sodium/iodide symporter (NIS) expression and response to neoadjuvant chemotherapy in patients with triple-negative breast cancer (TNBC).

Methods: The current retrospective study included 161 TNBC patients who received neoadjuvant chemotherapy followed by mastectomy. NIS expression was assessed via immunohistochemistry, graded semi-quantitatively from 0 to 3+. The Residual Cancer Burden (RCB) scale was used to evaluate the response to chemotherapy. Statistical analysis included Lilliefors tests and Kendall's tau correlation coefficient. Publicly available Cancer Genome Atlas datasets were analyzed to assess the relationship between NIS and FOXA1 expression.

Results: NIS immunopositivity was observed in 69.5% of TNBC samples compared to 63.3% GATA-3-positive and 31.0% of Mammaglobin-positive samples. While no significant correlation was found between NIS expression and age, TNM stage, or Ki-67, a statistically significant moderate positive correlation (τ = 0.481, p < 0.01) was identified between NIS expression and RCB index, indicating that higher NIS expression was associated with a poorer response to neoadjuvant chemotherapy. TCGA data analysis revealed a statistically significant increase in NIS mRNA expression in FOXA1-mutated TNBC samples compared to FOXA1-wild-type samples (p < 0.05). Younger patients exhibited higher Ki-67 levels (τ = -0.416, p < 0.05).

Conclusions: Higher NIS expression correlates with chemoresistance to neoadjuvant chemotherapy in TNBC patients. This phenomenon may be linked to FOXA1 activity, suggesting that NIS may represent a potential biomarker for chemoresistance in TNBC. The inverse correlation between patient age and Ki-67 levels may be associated with a different mutational landscape in younger patients.

Superficial fungal skin infections are common but often misdiagnosed, which may result in inappropriate treatment and the worsening of symptoms. An accurate and timely diagnosis is essential to differentiate these infections from similar conditions such as secondary syphilis, annular psoriasis, and pityriasis rosea. This single-centre prospective cohort study at the National Skin Centre, Singapore, evaluated the diagnostic agreement between direct microscopy and fungal culture. Between August and December 2022, 268 skin scrape samples were collected from 149 patients with suspected fungal infections. Microscopy identified 67 (25.0%) positives, while fungal culture detected 42 (16.7%) positives. Among the 252 samples tested with both methods, 213 (84.5%) showed concordant results (κ = 0.487, p < 0.0001), a finding that indicates moderate agreement. The most commonly cultured organisms were Trichophyton rubrum and T. mentagrophytes. Our findings suggest that both microscopy and fungal culture may be performed to prevent true-positive cases from being missed. However, in cases where cost is a concern, microscopy can be selected as an initial diagnostic tool. Should microscopy be negative in cases with high clinical suspicion for fungal infection or when empirical treatment fails, culture remains a valuable follow-up test. These findings support a stepwise diagnostic approach-using microscopy first, then followed by culture when necessary-to improve diagnostic accuracy while enabling timely treatment.