Search Results (3,658)

Background and Objective: Adverse pathology to high-risk prostate cancer (PCa) after radical prostatectomy (upgrading) poses a threat to risk stratification and treatment planning. The impact on sexual function, urinary continence, and health-related quality of life (HRQOL) remains unclear. Methods: From 2004 to 2024, 4189 patients with preop low-/intermediate-risk PCa (Gleason score 6 or 7a, PSA ≤ 20 ng/mL) underwent radical prostatectomy at our department and were analyzed. Primary endpoint was HRQOL, erectile function, and urinary continence. Secondary endpoint was rate of salvage therapies and biochemical-free survival. Propensity score matching was performed using “operative time”, “robot-assisted surgery”, “blood loss”, “nerve-sparing surgery”, “age”, and “BMI” to represent comparable surgical approach. Median follow-up was 39 months (Interquartile-range (IQR) 15–60). Key Findings and Limitations: Patients who were upgraded to high-risk PCa showed a higher rate of postoperative radiotherapy and androgen-deprivation therapy compared to patients who were not upgraded (21% vs. 7%, p < 0.001; 9% vs. 3%, p = 0.002). Five-year biochemical recurrence-free survival was 68% in the upgrading group vs. 84% in the no-upgrading group (p < 0.001). We saw no difference in patient-reported HRQOL, urinary continence, or erectile function. Multivariable analysis showed that postoperative upgrading was a significant risk for not achieving good overall HRQOL (OR: 0.77, 95% CI: 0.61–0.97, p = 0.028) during the follow-up. Conclusions and Clinical Implications: Although postoperative upgrading to high-risk PCa leads to worse oncologic outcomes and higher salvage therapy rates, this study indicates that its impact on health-related quality of life is minimal and should not deter a cautious approach to radical prostatectomy. Full article

Background and Objectives: Hysterectomy is a common non-obstetric procedure. Minimally invasive techniques, such as laparoscopy and robot-assisted surgery, have replaced open surgery for benign gynecologic conditions. Robotic surgery offers reduced blood loss and shorter hospital stays but is limited by high costs. Articulating laparoscopic instruments aim to replicate robotic dexterity cost-effectively. However, comparative data on these two approaches in hysterectomy are limited. Materials and Methods: This multicenter study analyzed the outcomes of hysterectomies for benign gynecological diseases using articulating laparoscopic instruments (prospectively recruited) and robot-assisted surgery (retrospectively reviewed). The surgeries were performed by minimally invasive gynecological surgeons in South Korea, Japan, and Taiwan. The baseline characteristics, operative details, and outcomes, including operative time, blood loss, complications, and hospital stay, were compared. Statistical significance was set at p < 0.05. Results: A total of 151 patients were analyzed, including 67 in the articulating laparoscopy group and 84 in the robot-assisted group. The operating times were comparable (114.9 vs. 119.9 min, p = 0.22). The articulating group primarily underwent dual-port surgery (79.1%), whereas the robot-assisted group required four or more ports in 71.4% of the cases (p < 0.001). Postoperative complications occurred in both groups, without a significant difference (9.0% vs. 3.6%, p = 0.17). No severe complications or significant differences in the 30-day readmission rates were observed. Conclusions: Articulating laparoscopic instruments provide outcomes comparable to robot-assisted surgery in hysterectomy while reducing the number of ports required. Further studies are needed to explore the learning curve and long-term impact on surgical outcomes. Full article

Alzheimer’s disease (AD) is a progressive neurodegenerative disorder characterized by cognitive decline, memory loss, and neuronal dysfunction. It is driven by the accumulation of amyloid-beta (Aβ) plaques, Tau protein hyperphosphorylation, oxidative stress, and neuroinflammation. Resveratrol (RSV) is a natural polyphenolic compound found in grapes, berries, and red wine that has garnered attention for its potential neuroprotective properties in combating AD. The neuroprotective effects of RSV are mediated through the activation of sirtuins (SIRT1), inhibition of Aβ aggregation, modulation of Tau protein phosphorylation, and the attenuation of oxidative stress and inflammatory responses. RSV also enhances mitochondrial function and promotes autophagy, which are important processes for maintaining neuronal health. Preclinical studies have demonstrated its efficacy in reducing Aβ burden, improving cognitive performance, and mitigating synaptic damage; however, challenges such as poor bioavailability, rapid metabolism, and limited blood–brain barrier penetration restrict its clinical applicability. Recent technological advances and selected modifications are being explored to overcome these limitations and enhance its therapeutic efficacy. This review summarizes the multifaceted neuroprotective mechanisms of RSV, the synergistic potential of natural compounds in enhancing neuroprotection, and the advancements in formulation strategies aimed at mitigating AD pathology. Leveraging the therapeutic potential of natural compounds represents a compelling paradigm shift for AD management, paving the way for future clinical applications. Full article

Background: Accumulating evidence indicates that SARS-CoV-2 infection results in long-term multiorgan complications, with the kidney being a primary target. This study aimed to characterize the long-term transcriptomic changes in the kidney following coronavirus infection using a murine model of MHV-1-induced SARS-like illness and to evaluate the therapeutic efficacy of SPIKENET (SPK). Methods: A/J mice were infected with MHV-1. Renal tissues were collected and subjected to immunofluorescence analysis and Next Generation RNA Sequencing to identify differentially expressed genes associated with acute and chronic infection. Bioinformatic analyses, including PCA, volcano plots, and GO/KEGG pathway enrichment, were performed. A separate cohort received SPK treatment, and comparative transcriptomic profiling was conducted. Gene expression profile was further confirmed using real-time PCR. Results: Acute infection showed the upregulation of genes involved in inflammation and fibrosis. Long-term MHV-1 infection led to the sustained upregulation of genes involved in muscle regeneration, cytoskeletal remodeling, and fibrotic responses. Notably, both expression and variability of SLC22 and SLC22A8, key proximal tubule transporters, were reduced, suggesting a loss of segment-specific identity. Further, SLC12A1, a critical regulator of sodium reabsorption and blood pressure, was downregulated and is associated with the onset of polyuria and hydronephrosis. SLC transporters exhibited expression patterns consistent with tubular dysfunction and inflammation. These findings suggest aberrant activation of myogenic pathways and structural proteins in renal tissues, consistent with a pro-fibrotic phenotype. In contrast, SPK treatment reversed the expression of most genes, thereby restoring the gene profiles to those observed in control mice. Conclusions: MHV-1-induced long COVID is associated with persistent transcriptional reprogramming in the kidney, indicative of chronic inflammation, cytoskeletal dysregulation, and fibrogenesis. SPK demonstrates robust therapeutic potential by normalizing these molecular signatures and preventing long-term renal damage. These findings underscore the relevance of the MHV-1 model and support further investigation of SPK as a candidate therapy for COVID-19-associated renal sequelae. Full article

Background/Objectives: Trochanteric femoral fractures pose significant surgical challenges, particularly in elderly patients. Intramedullary nailing (IMN) and plate fixation (PF) are the primary operative strategies, yet their comparative efficacy and safety remain debated. This meta-analysis synthesizes randomized controlled trials (RCTs) to evaluate clinical, functional, perioperative, and biomechanical outcomes of IMN versus PF specifically in trochanteric fractures. Methods: A systematic search of six databases was conducted up to 20 May 2024, to identify RCTs comparing IMN and PF in adult patients with trochanteric femoral fractures. Data extraction followed PRISMA guidelines, and outcomes were pooled using random-effects models. Subgroup analyses examined the influence of fracture stability, implant type, and patient age. Risk of bias was assessed using the Cochrane RoB 2.0 tool. Results: Fourteen RCTs (n = 4603 patients) were included. No significant differences were found in reoperation rates, union time, implant cut-out, or mortality. IMN was associated with significantly reduced operative time (MD = −5.18 min), fluoroscopy time (MD = −32.92 s), and perioperative blood loss (MD = −111.68 mL). It also had a lower risk of deep infection. Functional outcomes and anatomical results were comparable. Subgroup analyses revealed fracture stability and nail type significantly modified operative time, and compression screws were associated with higher reoperation rates than IMN. Conclusions: For trochanteric femoral fractures, IMN and PF yield comparable results for most clinical outcomes, with IMN offering some advantages in surgical efficiency and perioperative morbidity, though functional outcomes were comparable. Implant selection and fracture stability influence outcomes, supporting individualized surgical decision making. Full article

The impact of Oedema Disease produced by Shiga toxigenic Escherichia coli (STEC) in swine is increasing in some production countries due to increasing limitations on treatment with antimicrobials and zinc oxide, either because of the increased prevalence of multi-resistant strains or because of legal restrictions. The main pathological effect of Shiga toxin 2e is represented by damage to the endothelial cells of the blood vessel walls, leading to liquid extravasation and oedema formation in multiple tissues. These oedemas are generally easily identifiable in acute clinical cases. However, disease caused by Shiga toxin can occur without any externally visible oedema in the pigs, as observed in the subclinical presentation of Oedema Disease. It also causes productive losses, so it is important to identify and/or diagnose cases to set up control measures in order to optimize production and health. This article includes a comprehensive review of lesions and signs caused by Shiga toxin toxicosis in pigs, as well as other insights about the aetiology and epidemiology of STEC in pigs, and the effect of Shiga toxin recombinant toxoid vaccines in reducing these clinical and subclinical signs under field conditions. Full article

Background: The long-term clinical and laboratory results of a 33-year follow-up of a Greek family with abetalipoproteinemia (ABL) are described. Case Report: The patients (two brothers and their sister, aged 57, 49, and 62 years, respectively) are still alive, being under close surveillance. In two of the three patients, diarrhea appeared in early infancy, while in the third, it appeared during adolescence. CNS symptomatology worsened after the second decade of life. At the same time, night blindness appeared in the advanced stages of the disease, resulting in almost complete loss of vision in one of the male patients and severe impairment in the other. The diagnosis was based on the clinical picture, ophthalmological findings, serum lipid estimations, and presence of peripheral acanthocytosis. All patients exhibited typical serum lipidemic profile, ophthalmological findings, and acanthocytes in the peripheral blood. During the follow-up period, strict dietary modifications were applied, including the substitution of fat with medium-chain triglycerides (MCT oil). After 33 years since the initial diagnosis, all patients are alive without any sign of liver dysfunction despite continuous use of MCT oil. However, symptoms from the central nervous system and vision impairment worsened. Conclusion: The course of these patients suggests that the application of a modified diet, including MCT oil, along with close surveillance, could prolong the survival of patients without significant side effects from the liver. Full article

Background: Multisegmental lumbar degenerative disease (ms-LDD) is a common condition in older adults, often requiring surgical intervention. While rigid stabilization remains the gold standard, it is associated with complications such as adjacent segment disease (ASD), higher blood loss, and longer recovery times. The Dynesys dynamic stabilization system offers an alternative by preserving motion while stabilizing the spine. However, data comparing Dynesys with fusion in multisegmental cases are limited. Objective: This study evaluates the clinical and radiographic outcomes of Dynesys dynamic stabilization versus rigid stabilization in the treatment of ms-LDD. Methods: A retrospective analysis was conducted on 53 patients (mean age: 62.25 ± 15.37 years) who underwent either Dynesys dynamic stabilization (n = 27) or PLIF (n = 26) for ms-LDD involving at least seven motion segments. Clinical outcomes were assessed using the Visual Analog Scale (VAS) and Oswestry Disability Index (ODI), while radiological parameters such as lumbar lordosis (LL), sagittal vertical axis (SVA), and spinopelvic parameters (pelvic incidence, pelvic tilt and, sacral slope) were analyzed. A two-stage surgical approach was employed in the Dynesys group to enhance osseointegration, particularly in elderly osteoporotic patients. Results: Both groups showed significant improvements in VAS and ODI scores postoperatively (p < 0.001), with no significant differences between them. However, the Dynesys group demonstrated superior sagittal alignment correction, with a significant increase in LL (p < 0.002) and a significant decrease in SVA (p < 0.0015), whereas changes in the rigid stabilization group were not statistically significant. Additionally, the Dynesys group had fewer complications, including a lower incidence of ASD (0 vs. 6 cases). The two-stage technique facilitated improved screw osseointegration and reduced surgical risks in osteoporotic patients. Conclusions: Dynesys dynamic stabilization is an effective alternative to rigid stabilization in ms-LDD, offering comparable pain relief and functional improvement while preserving motion and reducing ASD risk. The two-stage approach enhances long-term stability, making it particularly suitable for elderly or osteoporotic patients. Further long-term studies are needed to confirm these findings. Full article

Cardiovascular disease encompasses a wide group of conditions that affect the heart and blood vessels. Of these diseases, cardiomyopathies and arrhythmias specifically have been well-studied in their relationship to cardiac dyads, nanoscopic structures that connect electrical signals to muscle contraction. The proper development and positioning of dyads is essential in excitation–contraction (EC) coupling and, thus, beating of the heart. Three proteins, namely CMYA5, JPH2, and BIN1, are responsible for maintaining the dyadic cleft between the T-tubule and junctional sarcoplasmic reticulum (jSR). Various other dyadic proteins play integral roles in the primary function of the dyad—translating a propagating action potential (AP) into a myocardial contraction. Ca²⁺, a secondary messenger in this process, acts as an allosteric activator of the sarcomere, and its cytoplasmic concentration is regulated by the dyad. Loss-of-function mutations have been shown to result in cardiomyopathies and arrhythmias. Adeno-associated virus (AAV) gene therapy with dyad components can rescue dyadic dysfunction, which results in cardiomyopathies and arrhythmias. Overall, the dyad and its components serve as essential mediators of calcium homeostasis and excitation–contraction coupling in the mammalian heart and, when dysfunctional, result in significant cardiac dysfunction, arrhythmias, morbidity, and mortality. Full article

Background and Objectives: Total hip arthroplasty (THA) following pelvic osteotomy for developmental dysplasia of the hip (DDH) is technically challenging due to altered acetabular morphology. This study aimed to compare radiographic cup position and perioperative characteristics of THA after three common pelvic osteotomies—periacetabular osteotomy (PAO), shelf procedure, and Chiari osteotomy—with primary THA in Crowe type I DDH. Methods: A retrospective review identified 25 hips that underwent conversion THA after pelvic osteotomy (PAO = 12, shelf = 8, Chiari = 5) and 25 primary THAs without prior osteotomy. One-to-one matching was performed based on sex (exact match), age (within 5 years), and BMI (within 2 kg/m²) without the use of propensity scores. Cup inclination, radiographic anteversion, center-edge (CE) angle, and cup height were measured on standardized anteroposterior radiographs (ICC = 0.91). Operative time, estimated blood loss, and use of bulk bone grafts or reinforcement rings were reviewed. One-way ANOVA with Dunnett’s post hoc test and chi-square test were used for statistical comparison. Results: Cup inclination, anteversion, and CE angle did not differ significantly among groups. Cup height was significantly greater in the PAO group than in controls (29.0 mm vs. 21.8 mm; p = 0.0075), indicating a more proximal hip center. The Chiari and shelf groups showed upward trends, though not significant. Mean operative time tended to be longer after PAO (123 min vs. 93 min; p = 0.078). Bulk bone grafts and reinforcement rings were more frequently required in the PAO group (17%; p = 0.036 vs. control), and occasionally in Chiari cases, but not in shelf or control groups. Conclusions: THA after PAO is associated with higher cup placement and greater need for reconstructive devices, indicating increased technical complexity. In contrast, shelf and Chiari conversions more closely resemble primary THA. Preoperative planning should consider hip center translation and bone-stock restoration in post-osteotomy THA. Full article

Background/Objectives: Conventional ketogenic diets, although effective for weight loss, often contain high total and saturated fat intake, which leads to increased low-density lipoprotein cholesterol (LDL-C). Thus, the Healthy Ketogenic Diet (HKD) was developed to address these concerns. It emphasizes calorie restriction, limiting net carbohydrate intake to 50 g per day, prioritizing unsaturated fats, and reducing saturated fat intake. However, adherence to the HKD remains a challenge in urban, time-constrained environments. Therefore, this pilot randomized controlled trial aimed to investigate the effects of Healthy Ketogenic Diet Ready-To-Eat (HKD-RTE) meals (provided for the first month only) versus HKD alone on weight loss and metabolic parameters among overweight adults. Methods: Multi-ethnic Asian adults (n = 50) with a body mass index (BMI) ≥ 27.5 kg/m² were randomized into the HKD-RTE group (n = 24) and the HKD group (n = 26). Both groups followed the HKD for six months, with the HKD-RTE group receiving HKD-RTE meals during the first month. Five in-person workshops and mobile health coaching through the Nutritionist Buddy Keto app helped to facilitate dietary adherence. The primary outcome was the change in body weight at 6 months. Linear regression was performed on the change from baseline for each continuous outcome, adjusting for demographics and relevant covariates. Logistic regression was performed on binary weight loss ≥ 5%, adjusting for demographics and relevant covariates. Results: In the HKD group, participants’ adherence to the 50 g net carbohydrate target was 15 days, while that in the HKD-RTE group was 19 days over a period of 30 days. Participants’ adherence to calorie targets was 21 days in the HKD group and 23 days in the HKD-RTE. The average compliance with the HKD-RTE meals provided in the HKD-RTE group was 55%. The HKD-RTE group experienced a greater percentage weight loss at 1 month (−4.8 ± 3.0% vs. −1.8 ± 6.2%), although this was not statistically significant. This trend continued up to 6 months, with the HKD-RTE group showing a greater percentage weight reduction (−8.6 ± 6.8% vs. −3.9 ± 8.6%; p = 0.092). At 6 months, the HKD-RTE group had a greater reduction in total cholesterol (−0.54 ± 0.76 mmol/L vs. −0.05 ± 0.56 mmol/L; p = 0.283) and LDL-C (−0.43 ± 0.67 mmol/L vs. −0.03 ± 0.52 mmol/L; p = 0.374) compared to the HKD group. Additionally, the HKD-RTE group exhibited greater reductions in systolic blood pressure (−8.3 ± 9.7 mmHg vs. −5.3 ± 11.0 mmHg), diastolic blood pressure (−7.7 ± 8.8 mmHg vs. −2.0 ± 7.0 mmHg), and HbA1c (−0.3 ± 0.5% vs. −0.1 ± 0.4%) than the HKD group (not statistically significant for any). Conclusions: Both HKD-RTE and HKD led to weight loss and improved metabolic profiles. The HKD-RTE group tended to show more favorable outcomes. Short-term HKD-RTE meal provision may enhance initial weight loss, with sustained long-term effects. Full article

Background/Objectives: Senecio scandens Buch.-Ham. is a flavonoid-rich traditional medicinal plant with established immunomodulatory properties. However, the mechanisms underlying the immunoregulatory and intestinal protective effects of its flavonoid extract (Senecio scandens flavonoids—SSF) remain unclear. This study characterized SSF’s bioactive components and evaluated its efficacy against cyclophosphamide (CTX)-induced immunosuppression and intestinal injury. Methods: The constituents of SSF were identified using UHPLC/Q-Orbitrap/HRMS. Mice with CTX-induced immunosuppression were treated with SSF (80, 160, 320 mg/kg) for seven days. Immune parameters (organ indices, lymphocyte proliferation, cytokine, and immunoglobulin levels) and gut barrier integrity markers (ZO-1, Occludin, Claudin-1 protein expression; sIgA secretion; microbiota composition) were assessed. Network pharmacology combined with functional assays elucidated the underlying regulatory mechanisms. Results: Twenty flavonoids were identified in SSF, with six prototype compounds detectable in the blood. The SSF treatment significantly ameliorated CTX-induced weight loss and atrophy of the thymus and spleen. It enhanced splenic T- and B-lymphocyte proliferation by 43.6% and 29.7%, respectively; normalized the CD4⁺/CD8⁺ ratio (1.57-fold increase); and elevated levels of IL-2, IL-6, IL-10, TNF-α, IFN-γ, IgM, and IgG. Moreover, SSF reinforced the intestinal barrier by upregulating tight junction protein expression and sIgA levels while modulating the gut microbiota, enriching beneficial taxa (e.g., the Lachnospiraceae_NK4A136_group, Akkermansia) and suppressing pathogenic Alistipes. Mechanistically, SSF activated the TLR/MyD88/NF-κB pathway, with isoquercitrin identified as a pivotal bioactive constituent. Conclusions: SSF effectively mitigates CTX-induced immunosuppression and intestinal damage. These findings highlight SSF’s potential as a dual-functional natural agent for immunomodulation and intestinal protection. Subsequent research should validate isoquercitrin’s molecular targets and assess SSF’s clinical efficacy. Full article

Background and Objectives: The management of type 2 diabetes (T2D) extends beyond glycemic control, requiring a more global strategy that includes optimization of body composition, even more so in the context of sarcopenia and visceral adiposity, as they contribute to poor outcomes. Past reviews have typically been focused on weight reduction or glycemic effectiveness, with limited inclusion of new therapies’ effects on muscle and fat distribution. In addition, the emergence of incretin-based therapies and dual agonists such as tirzepatide requires an updated synthesis of their impacts on body composition. This review attempts to bridge the gap by taking a systematic approach to how current blood-glucose lowering therapies affect lean body mass, fat mass, and the risk of sarcopenia in T2D patients. Materials and Methods: Between January 2015 and March 2025, we conducted a narrative review by searching the PubMed, Scopus, and Web of Science databases for English-language articles. The keywords were combinations of the following: “type 2 diabetes,” “lean body mass,” “fat mass,” “body composition,” “sarcopenia,” “GLP-1 receptor agonists,” “SGLT2 inhibitors,” “tirzepatide,” and “antidiabetic pharmacotherapy.” Reference lists were searched manually as well. The highest precedence was assigned to studies that aimed at adult type 2 diabetic subjects and reported body composition results. Inclusion criteria for studies were: (1) type 2 diabetic mellitus adult patients and (2) reporting measures of body composition (e.g., lean body mass, fat mass, or muscle function). We prioritized randomized controlled trials and large observational studies and excluded mixed diabetic populations, non-pharmacological interventions only, and poor reporting of body composition. Results: Metformin was widely found to be weight-neutral with minimal effects on muscle mass. Insulin therapy, being an anabolic hormone, often leads to fat mass accumulation and increases the risk of sarcopenic obesity. Incretin-based therapies induced substantial weight loss, mostly from fat mass. Notable results were observed in studies with tirzepatide, demonstrating superior reduction not only in fat mass, but also in visceral fat. Sodium-glucose cotransporter 2 inhibitors (SGLT2 inhibitors) promote fat loss but are associated with a small yet significant decrease in lean muscle mass. Conclusions: Blood-glucose lowering therapies demonstrated clinically relevant effects on body composition. Treatment should be personalized, balancing glycemic control, cardiovascular, and renal benefits, together with optimal impact on muscle mass along with glycemic, cardiovascular, and renal benefits. Full article

Postmenopausal osteoporosis is estrogen-dependent and results in an imbalance between bone formation and resorption. The approved therapy is intended to reduce the risk and consequences of fractures, but still has a number of contraindications and associated adverse effects. Recently, oxytocin has been shown to have an anabolic effect on bone tissue, increasing the production of osteoblasts and inhibiting the activity of osteoclasts. Thus, this study aimed to examine the potential of oxytocin as a biomarker and therapeutic agent for postmenopausal osteoporosis. A PubMed search yielded 16 articles upon analysis of the inclusion and exclusion criteria. The results showed that, compared to women in the same age group without bone loss, those diagnosed with osteoporosis exhibited lower blood oxytocin levels, possibly related to a greater tendency towards fractures. The administration of oxytocin could be a promising strategy to enhance bone quality and, consequently, to reduce the incidence of fragility fractures; however, no human studies have been conducted regarding its use as a possible treatment. Thus, it is essential to increase the number of clinical trials in women with ovarian dysfunction and bone loss, in which oxytocin could become a viable therapeutic alternative. Full article

Laparoscopic urological surgery has become a cornerstone in the management of diverse urological pathologies, offering substantial advantages over traditional open approaches. These benefits include minimized incisions, reduced tissue trauma, decreased intraoperative blood loss, lower postoperative pain, shorter hospital stays, superior cosmesis, and accelerated recovery. Despite these advantages, laparoscopic surgery carries inherent risks, with major vascular injury (MVI) representing one of the most severe and potentially life-threatening complications. This review examines the incidence, etiologies, and management strategies for MVI in laparoscopic urological surgery, emphasizing the critical role of early recognition, standardized protocols, and surgical expertise in optimizing patient outcomes. Full article