Search Results (214)

Background and Objectives: Peripheral blood indices have been proposed as prognostic biomarkers in endometrial cancer, but most reports include mixed histological subtypes, do not control for benign uterine pathology that independently alters hematological profiles, and evaluate these indices in isolation. We evaluated all three categories head-to-head in a histologically homogeneous endometrioid cohort and formally tested whether they add prognostic information beyond established clinicopathological variables. Materials and Methods: Of 195 patients operated for endometrioid-type endometrial cancer between 2018 and 2024, 142 were included; adenomyosis or leiomyoma on final histopathology, active infection and hematological disease were exclusion criteria. Fourteen preoperative blood-derived indices spanning the three categories were analyzed as continuous variables. A pre-specified clinical model (age category, grade, FIGO stage) was compared with models adding the biomarkers using likelihood-ratio tests, Harrell’s concordance index, time-dependent areas under the curve, bootstrap internal validation, and influence diagnostics. Results: Median follow-up was 52.5 months; 34 patients (23.9%) died and 5-year overall survival was 74.1%. None of the conventional inflammatory ratios were associated with survival (SII p = 0.893; all others p ≥ 0.26). In the multivariable model, histologic grade and NRBC% remained associated with survival (NRBC% HR 3.30 per 1%, 95% CI 1.09–9.97, p = 0.034). Adding NRBC% to the clinical model improved fit (likelihood-ratio p = 0.039) but not discrimination (ΔC 0.006, 95% CI −0.041 to 0.053, p = 0.814), and no index retained significance after Benjamini–Hochberg adjustment. The NRBC% association disappeared on dichotomization at the detection limit and could not be estimated once the five patients with values above 0.30% were excluded. Conclusions: In a predominantly early-stage endometrioid endometrial cancer cohort, preoperative blood-derived indices added no measurable discriminatory information beyond established pathological variables. The NRBC% association rests on very few observations at the upper end of its distribution and is hypothesis-generating only. Full article

Background: Acute myeloid leukemia (AML) is biologically heterogeneous and associated with poor outcomes. Although oxidative stress contributes to AML pathogenesis, the prognostic value of related biomarkers remains uncertain. Objective: This study aimed to evaluate associations between oxidative stress-related biomarkers and prognosis in adults with AML, focusing on overall survival (OS), complete remission (CR), relapse, relapse-free survival (RFS), event-free survival (EFS), and early mortality. Methods: This PRISMA-compliant systematic review was registered in PROSPERO (CRD420261364956). MEDLINE/PubMed, Scopus, Cochrane Library, Science Citation Index, ClinicalTrials.gov, and WHO ICTRP were searched from January 2015 through 31 July 2026. Eligible studies included adults with AML, oxidative stress-related biomarkers measured in biological samples, and extractable prognostic data. Risk of bias was assessed using QUIPS and certainty of evidence using GRADE. Results: Thirteen of 537 records met the inclusion criteria; 203 supplementary reports yielded no additional studies. Investigated biomarkers included ROS-related phenotypes, antioxidant and redox-regulatory genes, glutathione metabolism, iron/inflammation-related markers, and oxidative DNA damage indicators. Adverse outcomes were associated with ROS-related phenotypes, combined ROS/aldehyde dehydrogenase activity, GPX3, GSTP1, ferritin, gamma-glutamyl transpeptidase-to-albumin ratio, SOD1, and glutathione-related metabolic profiles. Conclusions: These biomarkers may have prognostic value, particularly for OS, but heterogeneity limits clinical application. Standardized validation and integration into applicable risk models are required. Full article

Background/Objectives: Severe alcohol-associated hepatitis (SAH) is a complication of alcoholic liver disease associated with high mortality. Effective identification of factors predicting the course, outcome, and need for early liver transplantation (eLT) in patients with SAH is crucial. Acute-on-chronic liver failure (ACLF), a syndrome characterized by an acute decompensation of cirrhosis, failure of one or more organs, and high short-term mortality, can occur in SAH, and its impact on management, prognostication, and need for eLT should be clarified. Methods: This is a single-center, retrospective study of patients with SAH admitted to the ASST GOM Niguarda in Milan between April 2016 and May 2023. Results: One hundred patients were included. Median Maddrey’s discriminant function (MDF) was 72.1 (IQR 51.6–101.3), and the median model for end-stage liver disease—sodium (MELD-Na) score was 28.5 (IQR 25.0–32.5). At presentation, 57 patients (57%) had ACLF 0–1 (54 ACLF 0—no organ failure [OF] or single non-renal OF with serum creatinine < 1.5 mg/dl and no hepatic encephalopathy; 3 ACLF 1—defined by the presence of at least renal failure or any other single OF if associated with renal dysfunction and/or grade I–II hepatic encephalopathy), and 43 patients (43%) had ACLF 2–3 (31 ACLF 2—defined by the presence of two OFs, 12 ACLF 3—defined by the presence of three or more OFs). In the latter group, circulatory failure was present in two (4.65%) and respiratory failure in three (6.98%). SAH was the only precipitating factor in 3 (100%) and 39 (90.7%) patients with ACLF 1 and ACLF 2–3, respectively, with infection being an associated factor in 5 (11.63%) and GI bleeding in 2 (4.65%) of subjects with ACLF 2–3. Non-response to medical treatment (MT) was significantly higher in patients with ACLF 2–3 (38/43, 88.4%) than in those with ACLF 0–1 (25/57, 43.8%). ACLF 2–3 was associated with a corresponding higher need for eLT (ACLF 2–3: 15/43, 34.9% vs. ACLF 0–1: 10/57, 17.54%%; p = 0.0474). ACLF status at presentation (ACLF 2–3 vs. ACLF 0–1) has a similar predictive accuracy of outcome (death or liver transplantation [LT]) to MELD-Na (as a 1-unit increase) (3.261 [1.999; 5.318], concordance index 0.702 vs. 1.154 [1.094; 1.217], concordance index 0.708). Conclusions: ACLF 2–3 is a frequent presentation of SAH, 43% of the cases. Given that most of these patients do not respond to MT (approximately 90%), fast-track evaluation for LT is advised for patients with a favorable psycho-social profile. Full article

Background and Objectives: The triglyceride-to-high-density lipoprotein cholesterol ratio (TG/HDL-C) is a simple lipid index associated with insulin resistance and atherogenic dyslipidemia. Previous evidence has supported the TG/HDL-C ratio as a simple surrogate marker of insulin resistance and an adverse metabolic profile. However, its relationship with glycemic control in real-world patients with type 2 diabetes mellitus (T2DM) remains uncertain. This study evaluated the association between the TG/HDL-C ratio and poor glycemic control in patients with T2DM. Materials and Methods: This retrospective observational study included patients with T2DM followed in outpatient clinics. Poor glycemic control was defined as glycated hemoglobin A1c (HbA1c) ≥ 7%. The association between the TG/HDL-C ratio and glycemic control was assessed using group comparisons, Spearman correlation, tertile analysis, and multivariable logistic regression adjusted for age, sex, LDL-C, total cholesterol, insulin use, statin use, and fenofibrate use. Receiver operating characteristic (ROC) analysis was used to evaluate the discriminatory performance of the TG/HDL-C ratio for identifying poor glycemic control. A sensitivity analysis was performed after excluding patients receiving fenofibrate. Results: A total of 1001 patients with T2DM were included, of whom 568 (56.7%) had poor glycemic control. The mean age was 60.9 ± 11.4 years, and 57.1% of participants were women. The poor- and adequate-glycemic-control groups were comparable with respect to age and sex. The TG/HDL-C ratio was higher in patients with HbA1c ≥7% than in those with HbA1c < 7% [3.35 (2.35–5.00) vs. 2.74 (1.87–3.82), p < 0.001] and increased progressively across tertiles. In multivariable analysis, the TG/HDL-C ratio remained associated with poor glycemic control after adjustment for available covariates (OR: 1.201, 95% CI: 1.125–1.282, p < 0.001). The association remained significant after excluding fenofibrate users. ROC analysis showed modest discrimination (AUC: 0.601, 95% CI: 0.566–0.636). Conclusions: The TG/HDL-C ratio was associated with poor glycemic control in patients with T2DM, showing a graded association across tertiles. However, its standalone discriminatory performance is modest. Given its modest discriminatory performance, the TG/HDL-C ratio should not be considered a standalone diagnostic or predictive tool for poor glycemic control; rather, it may serve as an accessible adjunctive metabolic marker associated with an adverse glycemic and lipid profile. Full article

Background: Technostress has emerged as a growing occupational health concern in increasingly digitalized workplaces. Although its psychological consequences have been extensively investigated, little is known about its potential association with metabolic health and insulin resistance. This study aimed to evaluate the relationship between technostress and insulin resistance risk using four validated surrogate markers in a large cohort of Spanish workers. Methods: A cross-sectional study was conducted among 104,175 Spanish workers who underwent routine occupational health assessments. Technostress was assessed using a 15-item questionnaire covering five technostress dimensions and was analyzed using four operational categories (low, moderate, high, and very high). Insulin resistance risk was assessed using the triglyceride–glucose (TyG) index, TyG-body mass index (TyG-BMI), the metabolic score for insulin resistance (METS-IR), and the single-point insulin sensitivity estimator (SPISE). Sociodemographic characteristics, lifestyle habits, anthropometric measurements, and biochemical parameters were also recorded. Modified Poisson regression with robust variance estimation was used to estimate crude and adjusted prevalence ratios (PRs) for increased insulin resistance risk according to technostress level. Firth penalized logistic regression was additionally performed as a sensitivity analysis to address sparse-data bias and separation. Results: Higher technostress levels were associated with progressively less favorable anthropometric and metabolic profiles. The prevalence of increased insulin resistance risk rose significantly across technostress categories for all markers evaluated (p < 0.001). For TyG, prevalence increased from 3.8% in the low technostress group to 54.3% in the very high technostress group. Corresponding increases were observed for TyG-BMI (0.2% to 78.2%), METS-IR (0.0% to 45.2%), and elevated SPISE-IR values (0.0% to 57.5%). After adjustment for age, sex, educational level, physical activity, adherence to the Mediterranean diet, and smoking status, higher technostress remained associated with a higher prevalence of increased insulin resistance risk. A clear graded cross-sectional pattern was observed, with the strongest associations found among workers reporting very high technostress. Conclusions: Higher technostress was associated with a higher prevalence of increased insulin resistance risk according to TyG, the primary outcome, with a clear graded cross-sectional pattern across technostress categories. Associations were also observed for the secondary BMI-containing indices (TyG-BMI, METS-IR, and SPISE-IR), which should be interpreted as complementary rather than independent evidence. Given the cross-sectional design and the pronounced clustering of technostress with adiposity and lifestyle characteristics, residual confounding cannot be excluded and causal inference is not possible. Full article

Background: Despite advances in prostate cancer (PC) radiotherapy, including intensity-modulated radiotherapy (IMRT), volumetric modulated arc therapy (VMAT), and stereotactic body radiotherapy (SBRT), genitourinary (GU) and gastrointestinal (GI) toxicities remain important complications. Identifying reliable predictors is essential for personalized treatment. Objective: The aim of this study was to summarize current evidence on clinical, dosimetric, immunological, and genetic predictors of acute and late GU and GI toxicities after PC radiotherapy. Materials and Methods: A structured literature review of studies published between 2000 and 2026 was conducted using PubMed, Scopus, and Europe PMC. Eligible studies included clinical investigations, randomized controlled trials, meta-analyses, and reviews assessing toxicity according to RTOG and/or CTCAE criteria. Results: GU toxicity was associated with pretreatment International Prostate Symptom Score (IPSS), large prostate volume, prior TURP, smoking, alpha-blocker use, and bladder/urethral dose. GI toxicity correlated with rectal dose–volume parameters, anorectal irradiation, anticoagulant therapy, and cardiovascular comorbidities. Acute grade ≥ 2 toxicity predicts late toxicity. Preliminary data from small single-center cohorts associate elevated IL-6, TGF-β1, TNF-α, and systemic immune-inflammation index with higher toxicity risk, and higher lymphocyte counts with lower risk; these findings require prospective validation. The PROSTOX radiogenomic signature is promising for the prediction of late GU toxicity but still requires independent external validation in larger, ethnically diverse cohorts with longer follow-up, and is not currently suitable for routine clinical decision-making. Conclusions: GU and GI toxicities have distinct predictive profiles. Integrating clinical, dosimetric, immunological, and genetic factors may improve personalized radiotherapy, although prospective multicenter validation remains necessary. Full article

Background: Sodium-glucose cotransporter 2 (SGLT2) inhibitors, originally developed as glucose-lowering agents for type 2 diabetes mellitus, have been shown in large, randomized trials to improve clinical outcomes in heart failure (HF) across the ejection fraction (EF) spectrum. The imaging-derived and hemodynamic changes that accompany these benefits remain incompletely characterized, and it is not known whether the patterns of cardiac remodeling observed differ between HF with reduced ejection fraction (HFrEF, left ventricular ejection fraction [LVEF] ≤ 40%) and HF with preserved ejection fraction (HFpEF, LVEF ≥ 50%). This systematic review synthesized randomized evidence on the effects of SGLT2 inhibitors on cardiac remodeling parameters and described the patterns observed in each phenotype. Methods: PubMed/MEDLINE, Scopus and Embase were searched for randomized controlled trials (RCTs) published between February 2016 and March 2026. Eligible studies enrolled adults with chronic HF receiving an SGLT2 inhibitor, included a non-SGLT2-inhibitor comparator and assessed cardiac structure, function or loading by echocardiography, cardiac magnetic resonance (CMR) or cardiac catheterization over at least three months. Risk of bias was assessed with Cochrane RoB 2, separately for each outcome domain and targeting the effect of assignment to intervention, and certainty of evidence with GRADE, separately by phenotype and imaging modality. A structured narrative synthesis following Synthesis Without Meta-analysis (SWiM) guidance that prioritized the direction, magnitude and precision of randomized between-group treatment effects was performed. Results: Fourteen publications from thirteen unique RCTs (1232 participants) were included: four trials enrolled HFrEF (LVEF ≤ 40%), five enrolled mixed reduced and mildly reduced EF cohorts (LVEF < 50% or 35–49%), four enrolled HFpEF (LVEF ≥ 50%) and one enrolled a mixed ejection-fraction population. No trial enrolled an exclusively HFmrEF population. In reduced EF, the direction of effect on LV volumes favored SGLT2 inhibition in four of eight trials reporting volumes, but the estimates were not compatible in magnitude, and the one adequately powered trial at low risk of bias (EFFORT) was neutral; the largest volumetric estimates came from EMPA-TROPISM, which published no adjusted between-group estimate. The only prespecified, adjusted and confidence-interval-bearing volumetric estimates were those of SUGAR-DM-HF (left ventricular end-systolic volume index −6.0 mL/m², 95% CI −10.8 to −1.2; end-diastolic volume index −8.2 mL/m², 95% CI −13.7 to −2.6). The global longitudinal strain improved in the trial with blinded core-laboratory reading (EFFORT −1.44%, 95% CI −2.42 to −0.46), but effect sizes in the open-label trials without stated reader blinding were two to three times larger, and the CMR-derived strain was unchanged. In HFpEF, volumes, EF, mass and strain were unchanged throughout. The most secure finding of the review was invasive: in CAMEO-DAPA, dapagliflozin reduced pulmonary capillary wedge pressure at rest by 3.5 mmHg (95% CI −6.6 to −0.4) and at peak exercise by 5.7 mmHg (95% CI −10.8 to −0.7). NT-proBNP results were directionally inconsistent, and the trials in which NT-proBNP was a prespecified primary endpoint (Empire HF, CANDLE) were neutral. Certainty of evidence was very low for 18 of 20 evidence profiles and low for the remaining two. Conclusions: Randomized imaging and hemodynamic studies suggest phenotype-related differences in the cardiac remodeling associated with SGLT2 inhibitor therapy. In studies enrolling patients with reduced EF, treatment was associated predominantly with reverse remodeling of left ventricular volumes and modest improvements in myocardial function, whereas in preserved EF, the observed changes were mainly confined to filling pressures and diastolic function, with no consistent evidence of left ventricular volumetric remodeling. Given the limited number of studies, substantial heterogeneity, and the overall low certainty of evidence, these findings should be considered hypothesis-generating and warrant confirmation in adequately powered phenotype-specific mechanistic trials. Full article

A rapid reversed-phase ultra-high-performance liquid chromatography method with diode-array detection (RP-UHPLC-DAD) was developed and validated for the simultaneous determination of major bioactive phenolic compounds (hydroxytyrosol, tyrosol, and oleuropein) and triterpenic acids (maslinic and oleanolic acids) in table olives from major Greek cultivars. Existing chromatographic methods for table olives typically target either the phenolic compounds or the triterpenic acids, requiring separate protocols. The proposed method determines both classes simultaneously, resolving all five analytes (resolution, R_s ≥ 5) within a 20 min separation (25 min total run) using a single methanolic co-extraction, thereby reducing analysis time and increasing throughput relative to sequential approaches. This protocol was selected among four evaluated extraction procedures, based on simplicity and efficient analyte extraction. The method showed excellent linearity (R² > 0.999), along with satisfactory sensitivity, selectivity, accuracy, and precision across the tested ranges. Recoveries of 70.8–108.9% were obtained in three different matrices (Chalkidiki, Kalamata, and Throumba Thassou olives), indicating satisfactory applicability to complex foods. The samples differed in their analyte profiles, with hydroxytyrosol predominating in the Chalkidiki and Kalamata samples, whereas oleuropein was detected only in Throumba Thassou olives. Sustainability assessment using the Complementary Green Analytical Procedure Index (ComplexGAPI) indicated moderate greenness, while a Blue Applicability Grade Index score of 72.5 denoted good practical applicability. Full article

Background and Objectives: Oxidative stress and chronic inflammation are closely interconnected processes involved in colorectal cancer (CRC) development and progression. However, the relationships between oxidative stress biomarkers, emerging hematological inflammatory indices, clinicopathological characteristics, and survival outcomes remain insufficiently characterized. This study evaluated circulating levels of 8-epi-prostaglandin F2α (8-epi-PGF2α), malondialdehyde (MDA), and superoxide dismutase 1 (SOD1), together with conventional and novel inflammatory indices, including the mean corpuscular volume-to-lymphocyte ratio (MCVL) and cumulative inflammatory index (IIC), in patients with CRC. Materials and Methods: This prospective observational study included 140 patients with histologically confirmed CRC and 40 healthy controls. Serum concentrations of 8-epi-PGF2α, MDA, and SOD1 were measured by ELISA, and hematological inflammatory indices were calculated from complete blood counts. Associations with clinicopathological characteristics were evaluated using non-parametric analyses with correction for multiple testing where appropriate. Spearman correlations with false discovery rate correction were used to assess oxidative–inflammatory associations. Prognostic analyses included 24-month time-dependent receiver operating characteristic (ROC) analysis accounting for censoring, Kaplan–Meier analysis, and Cox proportional hazards regression for overall survival (OS) and progression-free survival (PFS). Results: CRC patients exhibited significantly higher serum levels of 8-epi-PGF2α (p = 0.016), MDA (p < 0.001), and SOD1 (p < 0.001) than controls. Oxidative stress biomarkers differed significantly across TNM stage, nodal status, and histological grade, although the observed patterns were not uniformly progressive with disease stage. After false discovery rate correction, MDA retained significant correlations with multiple hematological inflammatory parameters, whereas SOD1 showed a more restricted correlation profile and 8-epi-PGF2α showed no significant correlations. At 24 months, MDA demonstrated the highest time-dependent discrimination for OS (AUC = 0.920; bootstrap 95% CI: 0.834–0.978), whereas its discrimination for PFS was modest (AUC = 0.636; bootstrap 95% CI: 0.487–0.773). High MDA, defined by the internally derived 24-month threshold, was associated with shorter PFS after adjustment for age, sex, and TNM stage (HR = 2.49, 95% CI: 1.29–4.80; p = 0.006) and, separately, metastatic status (HR = 2.40, 95% CI: 1.22–4.72; p = 0.011). However, when modeled continuously, MDA was no longer significantly associated with PFS after multivariable adjustment. Conclusions: CRC was associated with increased circulating oxidative stress biomarkers, with MDA showing the most consistent relationships with systemic inflammatory parameters and survival outcomes. Its prognostic association with PFS was dependent on the modeling approach, while its high discrimination for 24-month OS should be interpreted cautiously because of the limited number and metastatic restriction of death events. These findings identify MDA as a promising candidate oxidative–inflammatory marker warranting external validation rather than an independently established prognostic biomarker. Full article

Background/Objectives: This study aimed to comprehensively evaluate the interaction between periodontal disease, sleep quality, and quality of life and to investigate the effects of the presence and severity of periodontal disease on individuals’ sleep patterns and oral health-related quality of life. Materials and Methods: A total of 195 individuals were included in the study. Participants’ sociodemographic data and dental habits were recorded. Sleep quality was assessed using the Pittsburgh Sleep Quality Index (PSQI), while the impact of oral health on quality of life was evaluated using the Oral Health Impact Profile-14 (OHIP-14). Results: A significant difference was observed in OHIP-14 scores among the groups (p < 0.001), with median values of 6, 13, and 22 in the healthy, gingivitis, and periodontitis groups, respectively. OHIP-14 scores also increased significantly with the stage and grade of periodontitis (p < 0.001). PSQI scores differed significantly among the groups (p < 0.001), with median values of 4, 8, and 10 in the healthy, gingivitis, and periodontitis groups, respectively. However, no significant differences were observed in total PSQI scores across the stages or grades of periodontitis. In addition, a strong positive correlation was found between total PSQI and OHIP-14 scores (r = 0.63, p < 0.001). Multiple linear regression analysis confirmed that periodontal status remained independently associated with both PSQI and OHIP-14 scores after adjusting for age, sex, education level, and smoking status, with periodontitis showing the strongest association in both models (PSQI: B = 5.03; OHIP-14: B = 15.80, both p < 0.001). Conclusions: A significant relationship was identified between periodontal disease, sleep quality, and oral health-related quality of life. Furthermore, the strong positive correlation between sleep quality and oral health-related quality of life suggests that deterioration in sleep quality may be associated with poorer oral health-related quality of life. These findings indicate that periodontal health is not limited to oral tissues but is also closely associated with an individual’s overall well-being. Full article

Flexural strength (FS) governs the structural performance of 3D-printed concrete (3DPC) under bending loads yet remains difficult to predict owing to the coupled influence of binder composition, supplementary cementitious materials, water-to-binder ratio, and fiber reinforcement geometry on interlayer fracture behavior. Much of this compositional diversity stems from supplementary cementitious materials, industrial by-products whose reuse as partial cement replacement lowers the embodied carbon of printable mixes. A machine learning framework was trained on 209 FS records covering OPC- and SAC-based systems (FS: 3.65–45.0 MPa; W/B: 0.15–0.65). Six composite features were constructed from physical principles, two of them specific to bending: Fiber_Pullout_Index encoding post-crack pullout energy and Binder_Efficiency capturing cement quality per unit water content at the fiber–matrix interface; Lasso regularization with the one-standard-error rule reduced the 19-variable space to 14 active predictors. Twenty regression algorithms spanning eight families were benchmarked under 30 independent partitions; the Friedman test rejected equal performance (${\chi }^2=337.02$, $p=4.88\times {10}^{-60}$) and all 19 pairwise Wilcoxon comparisons against CatBoost were Holm-significant. CatBoost ranked first (mean rank of 18.17/20; 30-run $R^2=0.9302\pm 0.0722$; seed-42 partition: $R^2=0.9557$; RMSE = 1.761 MPa; MAPE = 11.20%). n(W/B) emerged as the primary driver across SHAP, ALE and LIME, with a monotonic ALE profile spanning 8.99 MPa and no inflection over the full printable window; Binder_Efficiency ranked second (PDP range: 5.21 MPa), isolating cement grade and paste dilution as independent strength levers. Cross-conformal prediction provided finite-sample coverage guarantees without distributional assumptions (empirical coverage: 95.24%; conformity quantile: 3.83 MPa); bootstrap analysis put the epistemic component at a mean predictive SD of 0.946 MPa, a quarter of that quantile. External validation yielded $R^2=0.769$ (Pearson $R=0.923$, RMSE = 1.91 MPa), with 19 of 20 predictions (95.0%) within Bland–Altman 95% limits of agreement, confirming transfer to a source study withheld from model training. A graphical user interface packaging the 14-feature CatBoost pipeline supports mix design queries without programming. Full article

Background/Objectives: International Society of Urological Pathology (ISUP) Grade Group discordance between prostate biopsy and radical prostatectomy (RP) affects 25–50% of men with localized prostate cancer and has direct implications for active surveillance, nerve-sparing, and adjuvant-treatment decisions. We synthesized contemporary evidence on the frequency of biopsy-to-RP grade migration and on emerging imaging, molecular/genomic, and artificial-intelligence (AI)-based predictors of migration. Methods: MEDLINE (PubMed) was searched from 1 January 2010 to 5 May 2026, supplemented by citation searching of recent systematic reviews. Eligible studies reported paired biopsy–RP pathology under the modified 2005 Gleason or the 2014/2019 ISUP Grade Group system, with ≥50 paired cases. Risk of bias was assessed with QUIPS, PROBAST, and QUADAS-2; certainty of evidence was rated with a GRADE framework adapted for prognostic research. Synthesis followed the SWiM reporting guidance. Results: Thirty-seven primary studies and eight prior systematic reviews were included. Concordance ranged from 44% to ~70%, upgrading from 14% to 67%, and downgrading from 5% to 26%. Biopsy GG1 disease showed the highest absolute upgrading risk (55–67%). Four predictors reached moderate GRADE certainty: PI-RADS category, biopsy approach (combined vs. systematic), PSMA-PET maximum standardized uptake value, and PSA density (PSAD). Cribriform/intraductal carcinoma at biopsy, the Decipher genomic classifier, the Prostate Health Index, and machine-learning and radiomics models reached very low certainty; clinical nomograms reached low certainty; germline alterations as direct predictors reached very low certainty. PROBAST flagged the analysis domain as high risk in five of eight prediction-model studies, and only one of eight models was externally validated. Conclusions: Despite a decade of refinements in grading, imaging, biopsy technique, and molecular profiling, biopsy-to-RP grade discordance remains substantial. Contemporary evidence supports incorporating PI-RADS, biopsy approach, and PSAD into shared decision-making; emerging molecular and AI-based predictors require prospective external validation in adequately powered, geographically representative cohorts before routine clinical adoption. Full article

Background: Robotic-assisted spinal instrumentation is increasingly used to support implant placement, reduce radiation exposure, and improve operative workflow. However, UK NHS data describing early programme experience across elective and emergency practice remain limited. This study aimed to evaluate the feasibility, safety profile, and early learning curve of robotic-assisted spinal instrumentation in an unselected UK NHS cohort. Methods: A retrospective, single-centre, single-arm observational cohort study was conducted, including the first 50 consecutive patients treated from programme inception between June 2024 and January 2026. No exclusion criteria were applied, and each record represented one patient and one operation. Missing data were not imputed, and denominators were reported per variable. Learning curve effects were assessed using Spearman correlation and cumulative sum analysis. Wilson 95% confidence intervals were reported for complication rates. Results: The mean age was 61.9 years; 50% were male; mean body mass index was 29.0; and median Charlson Comorbidity Index was 3. Indications were degenerative disease in 74%, trauma in 24%, and deformity in 2%. Emergency admissions accounted for 18/50 cases. Robot-specific adverse events included abandonment or conversion in 2/50 cases and system malfunction in 1/50. Surgical complications occurred in 7/50 patients. On surgeon-reviewed routine post-operative imaging, no screw malpositions required revision and no durotomies or vascular injuries were recorded; this represents a clinical revision rate rather than a formal radiological measure of screw accuracy, for which blinded Gertzbein–Robbins grading was not performed. Cumulative sum analysis suggested a potential fluoroscopy change point around case 30, with the median fluoroscopy events falling from 151 to 16 thereafter. Emergency cases involved more instrumented levels, longer operative times, and more open surgery than elective cases. Conclusions: Robotic-assisted spinal instrumentation was feasible across a diverse UK NHS caseload from C1 to S2, with a low observed complication rate. The findings suggest a fluoroscopy learning curve threshold around case 30. Larger comparative studies with formal radiological accuracy assessment are required. Full article

Chronic coronary syndrome (CCS) is characterized by persistent low-grade inflammation and impaired resolution of inflammatory responses within the vascular wall. Specialized pro-resolving mediators (SPMs), including resolvins and maresins, play an essential role in terminating inflammation and restoring tissue homeostasis. This prospective observational study included 83 patients hospitalized due to stable angina or angina-equivalent symptoms. Serum concentrations of leukotriene B4 (LTB4), maresin-1 (MaR1), resolvin E1 (RvE1), resolvin D1 (RvD1), and prostaglandin E2 (PGE2) were determined using enzyme-linked immunosorbent assays. Associations between mediator concentrations and clinical characteristics—including sex, age, and body mass index (BMI)—were analyzed using nonparametric statistical tests with false-discovery-rate correction. Women, patients ≥65 years of age, and individuals with BMI ≥ 30 kg/m² demonstrated significantly higher concentrations of LTB4, MaR1, and RvD1. In contrast, higher RvE1 concentrations were observed in men, younger patients, and those with a BMI < 30 kg/m². PGE2 levels did not differ significantly between the analyzed subgroups. Multivariable analysis identified age, LTB4, and RvD1 as independent predictors associated with coronary artery disease in the studied cohort. Circulating lipid mediator profiles differ according to sex, age, and obesity status in patients with chronic coronary syndrome. These findings demonstrate differential circulating lipid mediator profiles associated with age, sex, and obesity in patients with chronic coronary syndrome. Whether these profiles reflect adaptive inflammatory resolution or impaired resolution requires further investigation. Full article

This study investigates the efficacy of early multimodal data fusion for identifying academic performance profiles and predicting academic risk in specialized postgraduate education under small-sample constraints ($n=51$ graduate students distributed across three independent cohorts). Student numerical grades and multi-source qualitative faculty evaluations (self-, peer-, and hetero-evaluation) were integrated at the feature level prior to modeling. To overcome the limitations of traditional small-sample validation, a multi-layered framework was deployed, combining non-linear Kernel Principal Component Analysis (KPCA), multi-method clustering consensus, bootstrap resampling (1000 iterations), stratified nested cross-validation, and an external cohort validation strategy. The analysis revealed a bimodal distribution of academic risk (low-risk: 71.4%, high-risk: 28.6%) with high consensus across unsupervised algorithms (Adjusted Rand Index values spanning 0.922–1.000). Supervised predictive models yielded an unbiased nested cross-validation accuracy of $0.980\pm 0.040$, while external cohort validation demonstrated generalizability with a mean cross-cohort accuracy of $0.970\pm 0.052$ and a mean AUC of $0.997\pm 0.001$ (95% CI: $0.996–0.998$). SHAP feature importance analysis identified Machine Learning (28.68%), Artificial Intelligence (17.93%), and Big Data (16.66%) as the primary drivers of risk differentiation. This study contributes a methodologically rigorous, moderately stable, and reproducible workflow for educational data mining in sample-constrained environments, providing actionable insights for evidence-based curriculum design and early pedagogical interventions. However, given the limited sample size, results should be interpreted as exploratory evidence rather than definitive population-level conclusions. Full article