Search Results (2,049)

Background/Objectives: To investigate the importance of ADC, SUVmax, and SUVmax/ADC values in the prognosis and biological behavior of prostate cancer. Methods: In this retrospective study, ADC measurements in diffusion MRI were made by two radiologists by correlating the lesions with the highest SUVmax value from Ga-68 PSMA PET/CT examinations of 81 patients with prostate cancer. The quantitative values were compared with histopathological grade, presence of perineural invasion, and lymph node and bone metastasis. Results: For D’Amico high-risk patients, a statistically significant difference among the ADC, SUVmax, and SUVmax/ADC measurements was reported (p < 0.001). Cut-off values were defined as 0.52 (×10⁻³ mm²/s) for ADC, 9.73 for SUVmax, and 20.28 for the SUVmax/ADC ratio (AUC = 0.887, 0.747, 0.817, respectively) for the high-risk categories. The Youden indices were 0.643, 0.405, and 0.437, respectively. In logistic regression, the SUVmax/ADC ratio was a significant predictor of the high-risk group (AUC = 0.844, p = 0.002), demonstrating superior performance to a model with individual ADC and SUVmax values (AUC = 0.796, p = 0.006). For the advanced-grade group, the SUVmax and SUVmax/ADC ratios differed significantly (p < 0.001). The CAPRA score showed significant correlations with all imaging biomarkers: negatively with ADC (rho = −0.456, p < 0.001) and positively with SUVmax (rho = 0.359, p = 0.001) and the SUVmax/ADC ratio (rho = 0.441, p < 0.001). The presence of perineural invasion had no significant correlation with any of the variables (p > 0.05). The presence of bone metastases and PSA and free PSA levels differed significantly (p = 0.003, p = 0.001, respectively). In the presence of lymph node metastasis, SUVmax and SUVmax/ADC ratios were found to be significant (p = 0.019, p = 0.01, respectively). In the survival (OS) analysis, a low ADC value was found to be associated with shorter survival (median OS: 61 vs. 106 months). Conclusions: Among advanced-grade and high-risk prostate cancer patients, ADC, SUVmax, and SUVmax/ADC values can be employed as alternative prognostic factors for predicting the biological behavior of the disease. Full article

Background: Locally advanced prostate cancer (PCa) is commonly treated with multimodal therapy; however, long-term outcomes of surgery alone are poorly defined. We investigated the potential and limitations of robot-assisted radical prostatectomy (RARP) as primary treatment without perioperative systemic therapy in patients with locally advanced PCa. Methods: We retrospectively analyzed 258 patients who underwent RARP with extended pelvic lymph node dissection between 2012 and 2022 with locally advanced PCa, defined as present if at least one of the following was met: clinical stage cT3b–T4; primary Gleason pattern 5; >4 biopsy cores with Grade Group 4 or 5; or more than one NCCN high-risk characteristic. Patients who received neoadjuvant or adjuvant therapy were excluded. Endpoints included biochemical recurrence-free survival, metastasis-free survival, cancer-specific survival, and predictors of persistent PSA. Results: Median follow-up was 60.6 months. Pathological stage ≥ pT3a occurred in 63.6% and nodal involvement (pN1) in 27.1%. Five-year BRFS, MFS, and CSS were 36.6%, 88.9%, and 98.3%, respectively. Persistent PSA occurred in 21.3%. Preoperative predictors included PSA > 40 ng/mL, clinical stage ≥ cT3a, and >4 biopsy cores with a Gleason score of 8–10; patients with ≥2 features had significantly poorer BRFS and MFS. Postoperative predictors of recurrence were pathological stage, lymphovascular invasion, and nodal involvement. Conclusions: RARP alone provided durable long-term cancer control in selected men with locally advanced PCa, whereas patients with multiple adverse features were unlikely to be cured with surgery alone. Careful risk stratification may identify candidates for surgical monotherapy and help avoid overtreatment, while others may benefit from multimodal therapy. Full article

Background and Objectives: To examine the prevalence of fibromyalgia syndrome (FMS) in patients with psoriasis (PsO) and psoriatic arthritis (PsA) and its impact on treatment patterns and biologic therapy adherence. Materials and Methods: This retrospective cohort study utilized electronic health records from the Meuhedet Health Maintenance Organization in Israel between 2000 and 2020. PsO patients were matched 1:4 with controls by age, sex, and ethnicity. We assessed FMS prevalence, comorbidity burden, and treatment patterns. Cox regression and linear models evaluated the association between FMS and biologic switching and duration, adjusting for confounders. Results: Among 61,003 PsO patients and 244,012 controls, FMS prevalence was higher in PsO (3.3% vs. 2.3%, OR = 1.45, 95% CI: 1.38–1.53, p < 0.001). Among PsO patients, those with FMS were predominantly female (81.1% vs. 49.8%, p < 0.001) and had a higher prevalence of PsA (33.6% vs. 7.7%, p < 0.001). They received biologics more frequently (10.2% vs. 2.7%, p < 0.001) and were more likely to require multiple biologic lines (4.2% vs. 0.7%, p < 0.001). In PsA patients receiving biologics, FMS was associated with reduced survival on first-line therapy (6.1 vs. 10.1 years), increased switching risk (HR = 1.82, 95% CI: 1.42–2.35), and shorter treatment duration (B= −0.97 years, p = 0.001). Conclusions: In PsO patients, especially those with psoriatic arthritis, FMS is linked to greater treatment complexity and shorter biologic therapy survival, underscoring the need for tailored management strategies. Full article

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) cellular entry is facilitated by transmembrane protease serine 2 (TMPRSS2), which is regulated by the androgen receptor (AR). Androgen deprivation therapy (ADT), widely used in prostate cancer treatment, may potentially modulate TMPRSS2 expression, affecting SARS-CoV-2 infection susceptibility and severity. We evaluated the impact of ADT on pulmonary TMPRSS2 expression in prostate cancer patients and analyzed differences in expression patterns associated with specific ADT regimens. We examined TMPRSS2 immunohistochemical expression in lung tissue from 20 consecutive autopsy cases of men with prostate cancer (6 receiving ADT at time of death), compared with non-ADT prostate cancer patients and age-matched women controls. Histoscores were calculated by assessing the percentage and intensity of pneumocyte TMPRSS2 expression. Prostate cancer patients receiving ADT showed significantly reduced pulmonary TMPRSS2 expression compared to non-ADT patients (mean histoscores: 152.7 vs. 225.0, p = 0.037) and age-matched women controls (mean histoscores: 152.7 vs. 238.0, p = 0.024). Direct AR antagonists (apalutamide, bicalutamide) produced greater TMPRSS2 suppression than Gonadotropin-Releasing Hormone modulators or androgen biosynthesis inhibitors. No significant correlation was observed between the TMPRSS2 expression and Gleason score, PSA levels, or underlying lung pathology. Our findings demonstrate that ADT significantly reduces pulmonary TMPRSS2 expression, with direct AR antagonists showing the strongest effect. This suggests a potential mechanistic explanation for differential COVID-19 susceptibility and provides a rationale for investigating AR-targeted therapies as potential protective interventions against SARS-CoV-2 infection severity. Full article

Background/Objectives: Comparative studies examining postoperative pain and cosmetic outcomes following single-port laparoscopic appendectomy (SLA) and three-port laparoscopic appendectomy (TLA) in pediatric patients with appendicitis have produced inconsistent results. We aimed to determine whether SLA offers practical benefits over TLA in terms of recovery-phase pain relief and long-term cosmetic satisfaction in pediatric patients. Methods: This prospective comparative study included children aged 15 years or younger who underwent laparoscopic appendectomy for uncomplicated acute appendicitis. The degree of pain reduction was compared between the SLA and TLA groups on postoperative days (PODs) 1, 2, and 7, both at rest and during coughing and ambulation, using the Visual Analog Scale for Pain (VASP). Global cosmetic satisfaction was assessed at 1 month and 3 years postoperatively using the Visual Analog Scale for Cosmesis (VASC). Scar perception was evaluated with the Patient and Parental Scar Assessment Scale (PSAS). The primary outcome was the degree of pain reduction during ambulation on POD7. The secondary outcome was global cosmetic satisfaction at 3 years. Propensity score matching (PSM) was used as a sensitivity analysis to control for baseline differences. Continuous variables were assessed for normality using the Shapiro–Wilk test. Results: Baseline characteristics were similar among 238 patients (127 SLA and 111 TLA). SLA resulted in significantly greater pain reduction during ambulation on POD7 (deltaVASP7_walk: −6.22 ± 2.60 vs. −5.06 ± 3.23, p < 0.01, mean difference = −1.16, Cohen’s d = 0.39). However, this difference did not reach the minimal clinically important difference (MCID) threshold of 1.3. PSM analysis with 82 matched pairs confirmed the results, with even larger effect sizes. At 3 years, the SLA group reported significantly higher cosmetic satisfaction (VASC: median 10 [9–10] vs. 8 [6–9], p < 0.001, r = 0.44), surpassing the MCID of 1.5. The TLA group scored worse in scar perception regarding color, stiffness, thickness, and irregularity. Mediation analysis indicated that 66% of the overall effect on cosmetic satisfaction was mediated by scar perception. Conclusions: Although SLA offers statistically significant yet clinically marginal benefits in early postoperative pain reduction, it provides substantial benefits in long-term cosmetic satisfaction compared with TLA in pediatric patients. Full article

Background: This study aimed to develop and evaluate machine learning (ML) models to predict biochemical recurrence (BCR) after robot-assisted radical prostatectomy (RARP). Methods: We retrospectively analyzed clinical data from 1125 patients who underwent RARP between July 2013 and December 2023. The dataset was divided into a training set (70%) and a testing set (30%) using a stratified sampling strategy. Five ML models were developed using the training set. Model performance was evaluated on the testing set using the area under the receiver operating characteristic curve (AUC), accuracy, sensitivity, specificity, and F1 scores. Additionally, model interpretability was assessed using SHapley Additive exPlanations (SHAP) values to determine the contribution of individual features. Results: Among the five ML models, the LightGBM model achieved the best prediction ability with an AUC of 0.881 (95%CI: 0.840–0.922) in the testing set. For model interpretability, SHAP values explained the contribution of individual features to the model, revealing that pathological T stage (pT), positive surgical margin (PSM), prostate-specific antigen (PSA) nadir, initial PSA, systematic prostate biopsy positive rate, seminal vesicle invasion (SVI), pathological International Society of Urological Pathology Grade Group (pGG), and perineural invasion (PI) were the key contributors to the predictive performance. Conclusions: We developed and validated ML models to predict BCR following RARP and identified that the LightGBM model with 8 variables achieved promising performance and demonstrated a high level of clinical applicability. Full article

Background: MicroRNA-379 (miR-379) has been reported to play a tumour-suppressing role in several cancer types. Our previous work demonstrated that miR-379 overexpression attenuates the metastatic spread of prostate cancer (PCa) both in vitro and in vivo. However, the underlying mechanisms remain poorly understood. Methods: To elucidate the mechanisms by which miR-379 affects metastases, we performed a cytokine array to identify secreted proteins modulated by miR-379 dysregulation in a bone microenvironment model. We then assessed the levels of the key candidate, and performed functional studies, including reporter assays, of the transcriptional regulation. Results: Prostate-specific antigen (PSA)—the clinically widely used blood biomarker for PCa—emerged as the most significantly affected secreted protein. We observed that PSA secretion increased following miR-379 inhibition and decreased with miR-379 overexpression, with parallel changes in intracellular PSA levels. However, our data suggests that miR-379 does not directly regulate PSA expression. Instead, miR-379 appears to downregulate androgen receptor (AR) expression by targeting its 3′-untranslated region (3′-UTR), thereby indirectly reducing PSA transcription through diminished AR-mediated promoter activation. Supporting this indirect mechanism, analysis of clinical samples from prostate cancer patients revealed an inverse correlation between expression of miR-379 in prostatic tissue and serum PSA levels. Furthermore, reduced miR-379 expression was associated with increased levels of AR immunostaining in malignant tissues. Conclusions: Taken together, these findings suggest that miR-379 negatively regulates PSA secretion indirectly via suppression of AR, and that the interplay between miR-379, AR, and PSA may contribute to the metastatic progression of PCa to bone. Full article

Background: Nurses play a central role in the management of inflammatory joint diseases (IJD), of which the success depends on patient adherence to treatment, self-monitoring, timely detection of adverse drug reactions (ADRs), and adopting a healthy lifestyle. This study sought to examine the opinions of patients with IJD regarding the educational and supportive contributions of nurses. Methods: The research is based on a cross-sectional survey of patients with IJD treated with biologic disease-modifying antirheumatic drugs (bDMARDs) in two rheumatology clinics in Plovdiv, Bulgaria, from the beginning of August 2024 to the end of January 2025. The group included patients of three diagnoses: (1) rheumatoid arthritis (RA), (2) psoriatic arthritis (PsA), and (3) axial spondyloarthritis (axSpA). Results: Regardless of the diagnosis, and after adjusting for covariates, patients rated the roles of nurses in disease treatment and management, the acquisition of self-injection skills for bDMARDs, the implementation of a healthy lifestyle, and the maintenance of psychological well-being at the higher end of the 0 to 4 scale. However, the axSpA patients were less affirmative in their responses compared to the RA and PsA patients. In the RA and PsA groups, the working patients were associated with the lowest ratings, followed by retirees with disability. Conclusions: Our findings indicate that nurse-led education in patient self-management skills is greatly appreciated by patients with IJD. Further developments in specialized training programs tailored to the specific needs of different diagnoses and in consideration of patients’ social status will lead to increased patient satisfaction and a better overall quality of life. Full article

Elevated cholesterol levels play important mitogenic roles. Pseurotin A (PsA) is a fermentation product that has recently been reported as a dual inhibitor of proprotein convertase subtilisin/kexin type 9 (PCSK9) secretion and protein-protein interaction (PPI) with the LDLR. PsA showed a high acute safety profile and therapeutic potential against metastatic castration-resistant prostate cancer (mCRPC). The study aims to uncover the chronic safety, distribution, and anti-mCRPC genomic and molecular mechanistic insights of PsA. A 90-day chronic safety assessment of PsA up to 80 mg/kg in Swiss albino mice showed no signs of hematological, biochemical, or major organ toxicity. PsA demonstrated rapid intravenous distribution and elimination in Swiss albino mice. PsA is biodistributed to multiple key organs but was not detected in the brain, indicating its inability to cross the blood-brain barrier. PsA effectively suppressed the recurrence of nude mice xenografted mCRPC, which was subjected to a neoadjuvant docetaxel and enzalutamide regimen, followed by surgical excision. Collected PsA and vehicle control-treated recurrent tumors were subjected to RNA-sequencing and pathway enrichment analysis (PEA) of differentially expressed genes (DEGs). PsA-treated tumors revealed multiple significantly enriched pathways associated with promoting tumor apoptosis and inhibiting both invasion and migration. The PPI network analyses for the downregulated DEGs displayed prominent networks of genes associated with the ubiquitin-proteasome system. Results provide comprehensive mechanistic and preclinical validations for PsA’s potential as a novel PC recurrence suppressive lead entity. Full article

Taxonomic clarity within the genus Antithamnion is critical for understanding its molecular phylogeny and biodiversity. Here we report Antithamnion hubbsii for the first time from the Korean coast. This finding highlights the need to re-evaluate its relationship with the previously reported, morphologically very similar A. nipponicum in this region, raising the question of whether the newly identified A. hubbsii represents a local variant of A. nipponicum or a recently introduced invasive species via nearby ports. Specimens collected from Gangneung were analyzed using plastid-encoded rbcL and psaA genes, confirming their identity as A. hubbsii. Morphological features such as indeterminate lateral axes, oppositely arranged pinnae and pinnules, and distinctive adaxial gland cells supported this identification. Molecular analyses revealed minimal divergence between A. hubbsii and A. nipponicum (1–3 bp in rbcL, none in psbA), and contrasting results from different species delimitation methods. Phylogenetic analyses nevertheless placed the Korean specimens in a strongly supported A. hubbsii/A. nipponicum clade. Taken together, our results suggest that the North American invasive A. nipponicum and the Korean A. hubbsii may represent a single species with broad intraspecific variation. Definitive resolution will require molecular analyses of the type specimens of both taxa. Full article

The need for prostate cancer (PCa)-specific biomarkers that enable more accurate detection of the disease and better prediction of tumor aggressiveness remains ongoing due to the low cancer specificity of PSA screening. Several potential mRNA markers for diagnosing PCa, in tissue and urine, have been reported in the literature. In this study, we aim to explore the potential of selected prostate-specific molecules and transcripts contained in small extracellular vesicles (sEVs) in semen to predict PCa risk reclassification for patients with moderately elevated PSA levels—a clinical scenario where identifying truly non-invasive biomarkers is especially critical. RT-qPCR analysis in semen sEVs successfully showed differential expression of KLK3 and PCA3 genes between PCa and healthy controls, whereas CREB3L4, CCNQ and DUSP23 levels were related to the severity or degree of PCa affectation. Our findings also present strong evidence that classifiers based on combined long transcript levels in semen sEVs serve as effective biomarkers. They can be used alone or in combination with blood PSA and/or semen citric acid levels to improve the diagnosis of PCa and assess its severity and disease progression with high accuracy. This strategy would allow a more comprehensive assessment, increase prognostic accuracy, and facilitate accurate clinical decision-making in the management of PCa. Full article

Bacteroides fragilis, a prominent commensal of the human gut microbiota, plays a vital role in immune system regulation through its capsular polysaccharide A (PSA), which requires a glycolipid anchor structurally reminiscent of lipid A. While canonical Escherichia coli lipid A acts as a potent TLR4 agonist contributing to septic shock and inflammatory disorders, certain B. fragilis-derived glycolipids demonstrate antagonistic effects, offering potential as anti-inflammatory agents. In this study, we report the synthesis and preliminary computational evaluation of a library of glycolipids inspired by B. fragilis lipid A. Three lipid As, including a tetra-acylated 1-phosphoryl lipid A analog (Tetra C-1), were synthesized and assessed using molecular docking simulations targeting the human TLR4/MD-2 complex. Docking results reveal that Tetra C-1 exhibits more favorable antagonist binding characteristics compared to the well-studied TLR4 antagonist Eritoran. This work highlights a microbiota-informed strategy for the development of novel TLR4 antagonists, potentially enabling targeted modulation of innate immunity for therapeutic applications in inflammatory diseases and as vaccine adjuvants. Full article

Background: We evaluated the long-term treatment outcomes of patients with clinically localized and locally advanced prostate cancer (PC) who underwent high-dose-rate brachytherapy (HDR-BT) combined with external beam radiotherapy (EBRT). The primary objective was to identify the optimal timing for discontinuing prostate-specific antigen (PSA) monitoring after HDR-BT. Methods: This analysis included 338 patients with PC who received HDR-BT combined with EBRT between 2006 and 2022 and had a minimum follow-up of 5 years. The patients were stratified based on their PSA levels, and factors associated with recurrence were identified. Results: The median observation period was 8.9 years (range, 5.0–19.0 years). The 10-year recurrence-free survival rate was 92.0%, with 26 recurrences. PSA levels at 5 and 7 years were significantly correlated with oncological outcomes after HDR-BT. Multivariate analysis revealed that a PSA level of >0.2 ng/mL at 5 years was an independent poor prognostic factor for recurrence (hazard ratio, 117.57; 95% confidence interval, 6.22–2223.37; p = 0.001). No patient with a PSA level of ≤0.2 ng/mL at 7 years developed recurrences. Conclusions: Based on our long-term data, we propose that PSA monitoring may be safely discontinued in patients with a PSA level of ≤0.2 ng/mL 7 years after HDR-BT because the risk of recurrence beyond this point is exceedingly low. Full article

(1) Background: Cranial neuropathy is a commonly encountered condition with various underlying etiologies. While carotid artery dissection (CAD) is a well-recognized cause of ischemic stroke, CAD-related cranial neuropathy is rare and poorly characterized. We have conducted a comprehensive review of the published literature to better characterize its clinical course and outcomes. (2) Methods: We systematically reviewed the PubMed, CENTRAL, Ovid MEDLINE, and Embase literature for CAD-related cranial neuropathy. Data extracted included demographics, affected cranial nerves, symptoms, time course, diagnostic approach, and therapeutic interventions. (3) Results: From 635 screened studies, 97 met the inclusion criteria, yielding data on 108 patients with CAD- or dissecting pseudoaneurysm (dPSA)-related cranial neuropathy. The hypoglossal nerve (CN XII) was most commonly affected (76%), and the distal cervical internal carotid artery was the most frequently involved segment (89%). Most patients (90%) were treated with antithrombotic therapy which included either antiplatelets (47%) or anticoagulants (43%). Thirteen patients (12%) underwent endovascular intervention, nearly all with a diagnosed dPSA (mean size, 14.8 mm). Outcomes were favorable, with 94% experiencing symptom improvement. (4) Conclusions: Despite inherent limitations, our study demonstrates that CAD-related cranial neuropathy is typically a benign condition that has excellent outcomes with medical management. Endovascular treatment is rarely performed and is primarily reserved for cases involving diagnosed dPSA. Full article

Background/Objectives: To develop an automated American Joint Committee on Cancer (AJCC) staging system for radical prostatectomy pathology reports using large language model-based information extraction and knowledge graph validation. Methods: Pathology reports from 152 radical prostatectomy patients were used. Five additional parameters (Prostate-specific antigen (PSA) level, metastasis stage (M-stage), extraprostatic extension, seminal vesicle invasion, and perineural invasion) were extracted using GPT-4.1 with zero-shot prompting. A knowledge graph was constructed to model pathological relationships and implement rule-based AJCC staging with consistency validation. Information extraction performance was evaluated using a local open-source large language model (LLM) (Mistral-Small-3.2-24B-Instruct) across 16 parameters. The LLM-extracted information was integrated into the knowledge graph for automated AJCC staging classification and data consistency validation. The developed system was further validated using pathology reports from 88 radical prostatectomy patients in The Cancer Genome Atlas (TCGA) dataset. Results: Information extraction achieved an accuracy of 0.973 and an F1-score of 0.986 on the internal dataset, and 0.938 and 0.968, respectively, on external validation. AJCC staging classification showed macro-averaged F1-scores of 0.930 and 0.833 for the internal and external datasets, respectively. Knowledge graph-based validation detected data inconsistencies in 5 of 150 cases (3.3%). Conclusions: This study demonstrates the feasibility of automated AJCC staging through the integration of large language model information extraction and knowledge graph-based validation. The resulting system enables privacy-protected clinical decision support for cancer staging applications with extensibility to broader oncologic domains. Full article