Search Results (2,596)

Background: Accurate identification of pediatric B-cell acute lymphoblastic leukemia (B-ALL) patients at increased risk of relapse remains a major clinical challenge, as relapse occurs in 10–20% of cases, including patients initially classified as low- or intermediate-risk. This study aimed to identify clinical, genomic, and measurable residual disease (MRD) related predictors of relapse in pediatric B-ALL. Methods: 51 pediatric patients with B-ALL were included and followed for a median of 30.5 months (IQR, 16–45.5). Patients were stratified according to relapse status. At diagnosis, all cases underwent comprehensive genomic characterization based on the 2022 WHO and ICC classifications, including SNP-array analysis to identify copy number alterations (CNA) involving recurrent B-ALL genes (IKZF1, CDKN2A/B, PAX5, ETV6, BTG1, EBF1, ERG, RB1, and PAR1) and to determine IKZF1^plus status. Clinical variables, including white blood cell count, cytogenetic risk, and MRD assessed by flow cytometry at day 15, day 33, and at the end of induction, were analyzed. Kaplan–Meier and Firth-penalized Cox regression analyses were performed to identify independent predictors of relapse. Results: 86.3% of patients were classified according to the 2022 WHO/ICC classifications, with high hyperdiploidy being the most frequent subtype. During follow-up, 11 patients relapsed. Relapse was significantly associated with high cytogenetic risk (p = 0.007) and showed a trend toward association with an adverse CNA profile (p = 0.075). Patients with >25% bone marrow blasts at day 15 (p < 0.001) and those with positive MRD at the end of induction (p = 0.017) had a significantly higher risk of relapse. In multivariable analysis, high genetic risk and positive end-of-induction MRD remained independent predictors of relapse, with hazard ratios (HRs) of 9.31 (95% CI, 1.55–56.1), p = 0.010, and 10.9 (95% CI, 2.39–49.9), p = 0.002, respectively. Conclusions: An integrated diagnostic strategy including SNP-array provides a high diagnostic yield. High-risk cytogenetic abnormalities and positive end-of-induction MRD are independent predictors of relapse in pediatric B-ALL. Their combined assessment at diagnosis and early treatment may improve risk stratification and may support personalized therapeutic approaches. Full article

Background/Objectives: Double-J (DJ) ureteral stents are prone to luminal occlusion, which causes renal dysfunction and complicates exchange. Risk stratification in chronically stent-dependent patients is poorly defined, and the management of confirmed occlusion is not standardised. We aimed to identify independent risk factors for DJ stent occlusion in a chronically stent-dependent population and to evaluate stent-type substitution at first confirmed occlusion. Methods: We conducted a single-centre retrospective cohort study at a tertiary urology service in Melbourne, Australia (January 2023 to December 2025). Patients requiring three or more sequential DJ replacements were eligible. Mechanical occlusion was defined as inability to pass a guidewire through the stent lumen at fluoroscopic exchange, an objective intraoperative surrogate; clinical failure events (nephrostomy conversion, septic admission, or acute kidney injury requiring intervention) were recorded separately. Midstream urine culture and pre-exchange renal ultrasound were obtained at each visit. Cox proportional hazards modelling with robust patient-level clustering was performed. Results: We analysed 125 ureters (97 patients) over a mean follow-up of 20.6 months. Occlusion occurred in 55 ureters (44.0%). Four predictors were robust to Bonferroni correction: indwelling urethral catheter (hazard ratio [HR] 4.62), urinary stone disease versus malignant disease (HR 4.02), retroperitoneal fibrosis versus malignant disease (HR 3.24), and bacteriuria at exchange (HR 2.76). Two further associations, Eastern Cooperative Oncology Group (ECOG) performance status 2 to 4 (HR 2.31) and prior pyelonephritis (HR 1.89), did not survive correction and are exploratory. After stent-type substitution at first occlusion, 43 of 55 ureters (78.2%) had no further occlusion without interval shortening. Summer accounted for 45.1% of events (p < 0.001). Conclusions: In chronically stent-dependent patients, several factors were independently associated with DJ stent occlusion, four of them robust to multiple-comparison correction. Stent-type substitution was associated with occlusion-free outcomes in most cases without interval shortening; because the analysis was uncontrolled and regression to the mean cannot be excluded, this observation is hypothesis-generating. All hazard estimates are exploratory in view of an events-per-variable ratio below ten and a survivor-selected cohort, and apply only to patients with established chronic stent dependency. Prospective randomised evaluation is warranted. Full article

Background: Oral lichen planus is a chronic oral potentially malignant disorder requiring timely diagnosis and long-term follow-up, yet its diagnostic pathway remains poorly characterised. This study assessed diagnostic and follow-up intervals in patients with oral lichen planus and explored associated clinical and healthcare-related factors. Methods: This retrospective cohort study included 199 patients with clinically and histopathologically confirmed oral lichen planus managed at the Oral Medicine Unit of the University of Murcia. Diagnostic time points were defined using an adapted Aarhus framework. Patient, primary care, specialist diagnostic and total intervals were analysed using multivariable quasi-Poisson regression. Loss to follow-up was assessed using Cox regression. Results: Older age was associated with longer patient, primary care and total intervals. Women had a shorter patient interval than men (IRR = 0.44; 95% CI: 0.21–0.91; p = 0.03), but a longer primary care interval (IRR = 3.09; 95% CI: 1.12–10.2; p = 0.04). Compared with erosive oral lichen planus, mixed and reticular forms showed shorter primary care intervals and shorter specialist diagnostic intervals, with IRRs ranging from 0.21 to 0.36 (all p < 0.01). Daily alcohol consumption was associated with the longest total interval. Older age was associated with a higher risk of loss to follow-up (HR = 1.02; 95% CI: 1.00–1.04; p = 0.01), whereas non-pharmacological treatment was associated with a lower hazard of loss to follow-up (HR = 0.31; 95% CI: 0.16–0.60; p < 0.001). Conclusions: Diagnostic delay in oral lichen planus is multifactorial and appears to depend on patient characteristics, clinical presentation and healthcare pathway factors. Improved recognition of erosive disease, clearer referral criteria and structured follow-up strategies may enhance care continuity. Full article

Background: Lipoprotein(a) [Lp(a)] has emerged as a key mediator of calcific aortic valve disease and is strongly linked to the development and progression of aortic stenosis (AS). Whether elevated Lp(a) influences disease severity, long-term prognosis, or both in patients undergoing transcatheter aortic valve implantation (TAVI) remains uncertain. Methods: This multicenter study included 213 patients with severe symptomatic AS undergoing TAVI between 2016 and 2018. Pre-procedural Lp(a) concentrations were measured using a standardized immunoturbidimetric assay. Associations with long-term all-cause mortality were evaluated using Kaplan–Meier analyses and Cox proportional hazards models. The relationship between Lp(a) and AS severity was assessed using correlation analyses, multivariable linear regression models, and restricted cubic spline analyses. Anatomical and hemodynamic measures included aortic valve calcium score (AVCS), peak aortic jet velocity (AV Vmax), and transvalvular pressure gradients. Results: During a median follow-up of 7.58 years (IQR 4.33–8.66 years), Lp(a) was not associated with all-cause mortality, irrespective of whether it was analyzed as a continuous variable, according to established clinical thresholds, or across quartiles. In contrast, higher Lp(a) concentrations were associated with greater valvular calcification and more severe hemodynamic obstruction. These associations remained significant after adjustment for age, sex, diabetes mellitus, and renal function. Restricted cubic spline analyses suggested predominantly linear associations without evidence of significant non-linearity. Conclusions: Elevated Lp(a) concentrations were associated with greater anatomical and hemodynamic severity of AS but not with long-term mortality after TAVI. These findings suggest that elevated Lp(a) is associated with greater anatomical and hemodynamic severity of calcific aortic valve disease but was not linked to long-term mortality after TAVI. Full article

Background/Objectives: Sex-based differences in asbestos exposure and tumor biology in pleural mesothelioma (PM) remain incompletely characterized. As an expert tertiary center, we sought to systematically characterize asbestos exposure by sex and assess biomarker prognostic relevance in surgically treated pleural mesothelioma. Methods: We conducted a retrospective, single-center cohort encompassing all patients who underwent surgical intervention for PM at our institution. Demographic characteristics, asbestos exposure history, tumor biomarker profiles, and survival outcomes were extracted from this database and supplemented by review of the electronic medical record. Sex differences in asbestos exposure and biomarker expression were assessed using Fisher’s exact test on an available-case basis, while logistic regression was used to identify predictors of documented asbestos exposure. Overall survival was estimated using Kaplan–Meier analysis; independent associations between biomarkers and mortality were determined via multivariable Cox proportional hazards models adjusted for age, sex, and histological subtype. Results: Between 2015 and 2024, 106 patients (75% males) underwent surgical intervention for PM, with a median follow-up of 4.4 years. The mean age at surgery was 67.5 years (Standard Deviation [SD], 11). The cohort predominantly consisted of patients with epithelioid histology (n = 86, 81%), followed by biphasic (n = 16, 15%), and sarcomatoid (n = 4, 4%) subtypes. Thirty (28.3%) were alive at last follow-up. Median overall survival was 15.6 months (95% Confidence Interval [CI], 13.8–25.4 months), and 5-year survival was 17.8%. Of 92 patients with available exposure data, 66 (72%) had documented exposure histories. Although most of these exposures were occupational (46, 78%), a striking disparity was observed between occupational exposures in males vs. females (44 [86%] vs. 2 [25%]; n = 8 classifiable females; p < 0.001). Multivariable analysis demonstrated that male sex was associated with increased odds of asbestos exposure (Adjusted Odds Ratio [OR_adj], 5.45; 95% Confidence Interval [CI], 1.90–16.35). PD-L1, Ki-67, or BAP1 expression were not associated with sex, age, or asbestos exposure. High Ki-67 (>15%) and PD-L1 (>15%) were associated with a four-fold and three-fold increased risk of mortality (Hazard Ratio_adj [HR_adj], 4.33 [95% CI, 1.85–10.13] and HR_adj, 2.80 [95% CI, 1.39–5.64], respectively), whereas BAP1 loss was not (HR_adj, 0.80; 95% CI, 0.45–1.44). Conclusions: Our findings underscore the potential value of sex-sensitive screening protocols that more comprehensively assess non-occupational asbestos exposure pathways and offer additional evidence regarding the prognostic relevance of PD-L1, Ki-67, and BAP1 in surgical patients. Full article

Background/Objectives: In-hospital cardiac arrest (IHCA) remains associated with poor survival, while the contribution of arrest etiology and early physiological markers to outcome remains incompletely defined. We examined associations between clinical, neurological, metabolic, and etiological factors and sustained return of spontaneous circulation (ROSC) lasting >20 min, 28-day survival, and 60-day mortality. Methods: This retrospective single-center cohort included 134 adults with confirmed IHCA requiring cardiopulmonary resuscitation at a tertiary university hospital with advanced transplant care between 2011 and 2015. Sustained ROSC and 28-day survival were analyzed using parsimonious Firth penalized logistic regression models, and 60-day mortality using Cox proportional hazards regression. Selected neurological and biomarker analyses were considered exploratory. Results: Sustained ROSC was achieved in 91 patients (67.9%), 33 (24.6%) survived to day 28, and 30 (22.4%) survived to day 60. Initial non-shockable rhythm was associated with lower odds of sustained ROSC (aOR 0.26, 95% CI 0.09–0.69) and 28-day survival (aOR 0.27, 95% CI 0.10–0.68), and with higher 60-day mortality (aHR 1.96, 95% CI 1.25–3.08). The presence of a potentially reversible cause was associated with more favorable outcomes, whereas active hematologic malignancy was associated with higher 60-day mortality (aHR 1.89, 95% CI 1.15–3.10). Exploratory analyses also showed associations of initially dilated pupils with lower 28-day survival and higher lactate with 60-day mortality. Among patients who survived beyond 24 h, higher BNP was associated with subsequent mortality. Conclusions: Non-shockable rhythm and the presence of a potentially reversible cause were consistently associated with outcomes following IHCA, while active hematologic malignancy was associated with poorer longer-term survival. Exploratory findings from lactate, initial pupillary assessment, and BNP may provide complementary prognostic information, although the BNP analysis was limited to patients who survived beyond 24 h. These findings require confirmation in contemporary multicenter cohorts and do not establish validated clinical prediction tools. Full article

Background/Objectives: Oligometastatic GIST, defined in this study as five or fewer metastatic lesions confined to a single organ, represents a distinct subset with a lower metastatic burden than widely metastatic disease and may have different prognostic and therapeutic considerations. Methods: We reviewed biopsy-proven oligometastatic GIST diagnosed between August 1998 and June 2025 from a prospectively maintained institutional database, collecting genomic, metastatic, treatment, ethnicity, and survival data. Overall survival (OS), calculated from diagnosis of oligometastatic disease, was estimated by Kaplan–Meier analysis and compared using the log-rank test. Hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated using Cox proportional hazards regression. Results: Of 525 subjects with GIST in our database, 96 (18.3%) had oligometastatic GIST (median age: 54 years; median OS from diagnosis of oligometastatic disease: 9.77 years). Most tested tumors were KIT-positive (91.6%), predominantly harboring KIT exon 11 alterations (69.5%). The most common metastatic sites were the liver (n = 44) and peritoneum (n = 37). Overall, 58 patients underwent surgery, including 55 cytoreductive procedures and 3 emergent operations for bleeding or obstruction. Among the cytoreductive procedures, indications included multifocal disease after tyrosine kinase inhibitor (TKI) response (n = 21), unifocal disease after TKI response (n = 18), unifocal progression on TKI (n = 13), and equivocal or undocumented TKI response (n = 3). Overall survival did not differ by liver versus peritoneal metastases (HR: 1.27; 95% CI, 0.59–2.70; p = 0.540) or Hispanic versus non-Hispanic ethnicity (HR: 0.81; 95% CI, 0.34–1.90; p = 0.624). Cytoreductive surgery combined with systemic therapy was associated with longer overall survival than systemic therapy alone (10.8 vs. 7.4 years; HR: 0.44; 95% CI, 0.22–0.89; p = 0.019). Conclusions: In this retrospective cohort, cytoreductive surgery combined with systemic therapy was associated with longer overall survival than systemic therapy alone. Full article

Background: Treatment strategies for myelodysplastic syndromes (MDS) range from supportive care to disease-modifying therapies, depending on risk stratification and patient characteristics. Hypomethylating agents (HMAs) remain the standard treatment for higher-risk disease, whereas allogeneic hematopoietic stem cell transplantation (allo-HSCT) is the only potentially curative option. This study evaluated real-world survival outcomes and prognostic factors in patients with MDS treated with HMAs or allo-HSCT. Methods: A total of 79 patients with MDS who received azacitidine, decitabine, or allo-HSCT were retrospectively analyzed. Overall survival (OS) was evaluated using Kaplan–Meier and Cox proportional hazards analyses. To address potential immortal time bias, a prespecified 6-month landmark analysis was additionally performed. Results: Median OS was 14.9 months (95% CI, 9.9–20.0) with azacitidine, 10.0 months (95% CI, 6.8–13.2) with decitabine, and 48.0 months (95% CI, 19.9–76.1) after allo-HSCT. Patients undergoing allo-HSCT were significantly younger and had better ECOG performance status than those receiving HMAs. After adjustment for age, ECOG performance status, and IPSS-R risk category, treatment modality remained significantly associated with OS in the multivariable Cox regression model. In the prespecified 6-month landmark analysis, the survival advantage associated with allo-HSCT remained significant, although the adjusted association was attenuated. Conclusions: In this real-world cohort of actively treated patients with MDS, allo-HSCT was associated with longer overall survival than HMAs. Although this association persisted after adjustment for major clinical confounders and in a landmark analysis addressing immortal time bias, residual confounding related to treatment selection cannot be excluded. These findings should therefore be interpreted as an association rather than evidence of a causal treatment effect. Full article

Background: Computed tomography (CT)-derived body composition has emerged as a promising prognostic biomarker in pancreatic ductal adenocarcinoma (PDAC). However, most previous studies have relied on baseline measurements and evaluated either resected or metastatic disease separately. We aimed to investigate the prognostic significance of both baseline and longitudinal CT-derived body composition changes in clinically distinct but therapeutically homogeneous cohorts of patients with PDAC receiving FOLFIRINOX. Methods: This retrospective single-center study included 98 consecutive patients with histologically confirmed PDAC treated with FOLFIRINOX between 2018 and 2025. Forty-seven patients underwent curative-intent resection followed by adjuvant modified FOLFIRINOX, whereas 51 patients with unresectable metastatic disease received first-line FOLFIRINOX. Skeletal muscle index (SMI) and visceral adipose tissue (VAT) were quantified on serial CT scans obtained at the third lumbar vertebral level before treatment and during therapy. Follow-up CT scans suitable for longitudinal body composition analysis were available for 46 of 51 patients (90.2%) in the metastatic cohort. Overall survival (OS), disease-free survival (DFS), and progression-free survival (PFS) were estimated using the Kaplan–Meier method. Univariable and multivariable Cox proportional hazards regression analyses were performed to identify independent prognostic factors. Results: Baseline CT-derived body composition parameters were not independently associated with survival in either cohort. In the resected cohort, preservation of visceral adiposity during treatment (follow-up VAT > 100 cm²) independently predicted improved OS in a multivariable model including three covariates (HR 0.460, 95% CI 0.220–0.960; p = 0.039). Median DFS and OS were 11.7 months (95% CI 6.5–16.9) and 20.9 months (95% CI 12.1–29.7), respectively. In the metastatic cohort, treatment-related skeletal muscle loss (ΔSMI) independently predicted inferior OS in a multivariable model including four covariates (HR 0.949, 95% CI 0.913–0.986; p = 0.008), while lung metastasis was also independently associated with worse survival (HR 5.792, 95% CI 1.880–17.841; p = 0.002). Median PFS and OS were 9.7 months (95% CI 8.0–11.4) and 12.7 months (95% CI 9.9–15.5), respectively. Conclusions: Longitudinal CT-derived body composition changes may provide additional prognostic information beyond baseline measurements in patients with PDAC receiving FOLFIRINOX. Preservation of visceral adiposity was associated with improved survival following curative-intent resection, whereas greater treatment-related skeletal muscle loss was associated with poorer survival in metastatic disease. These findings suggest that the prognostic relevance of body composition may vary according to disease stage and should be considered hypothesis-generating pending validation in larger prospective multicenter studies. Full article

Background/Objectives: Pleural effusions are frequently encountered on pre-procedural computed tomography (CT) scans in patients undergoing transcatheter aortic valve implantation (TAVI). While often regarded as a marker of congestion and advanced cardiovascular disease, their clinical and prognostic significance in contemporary TAVI populations remains poorly understood. This study investigated the relationship between AI-derived pleural effusion volume, cardiovascular dysfunction, and long-term mortality after TAVI. Methods: Consecutive patients undergoing transfemoral TAVI between 2016 and 2022 who had available pre-procedural CT imaging were retrospectively included. Pleural effusion volume was quantified using an artificial intelligence-based segmentation workflow and analyzed as categorical, continuous, log-transformed, and threshold-based variables. Associations with clinical and echocardiographic characteristics were evaluated using Spearman correlation analyses. Long-term mortality was assessed using Kaplan–Meier analysis, Cox proportional hazards regression, and restricted cubic spline models. Results: A total of 470 patients were included (median age 82 years, 50.9% male). Pleural effusion was present in 124 patients (26.38%), including 73 (15.53%) with small, 26 (5.53%) with moderate, and 25 (5.32%) with larger effusions. Increasing pleural effusion volume was associated with atrial fibrillation (AF) (rho = 0.189, p < 0.001), higher systolic pulmonary artery pressure (rho = 0.224, p < 0.001), lower tricuspid annular plane systolic excursion (rho = −0.236, p < 0.001), impaired right ventricular–pulmonary arterial coupling (rho = −0.267, p < 0.001), lower stroke volume index (rho = −0.229, p < 0.001), and reduced left ventricular ejection fraction (rho = −0.221, p < 0.001). Despite these associations, pleural effusion volume was not associated with long-term mortality in univariable analyses, multivariable Cox regression models, or restricted cubic spline analyses. In the fully adjusted model, log-transformed pleural effusion volume was not independently associated with mortality (HR 1.00, 95% CI 0.93–1.08; p = 0.976). Conclusions: AI-derived pleural effusion volume is associated with markers of cardiovascular congestion and adverse hemodynamic remodeling in patients undergoing TAVI. However, pleural effusion burden does not independently predict long-term mortality, suggesting that its value lies primarily in phenotyping cardiovascular disease severity rather than risk stratification. Full article

Background/Objectives: Malnutrition adversely affects the clinical course of acute myeloid leukemia (AML), yet comparative data on objective nutritional indices remain limited. Methods: This study evaluated the prognostic performance of four indices—Controlling Nutritional Status (CONUT), Simple CONUT, Prognostic Nutritional Index (PNI), and Nutritional Risk Index (NRI)—on overall survival (OS) alongside the European LeukemiaNet (ELN) 2022 risk classification. Pre-treatment parameters of 236 newly diagnosed AML patients were retrospectively analyzed using Receiver Operating Characteristic (ROC) curves and multivariate Cox regression models. Results: In ROC analysis, only NRI demonstrated significant discriminative performance in predicting OS (Area Under the Curve = 0.637, p < 0.001), whereas CONUT, Simple CONUT, and PNI lacked statistical significance. Patients with low NRI scores had significantly worse survival than the high NRI group (median OS: 16.8 months versus not reached, p = 0.004), particularly within the ELN favorable risk category (2-year OS: 59.6% versus 93.5%, p = 0.022). Multivariate analysis established NRI as an independent predictor of mortality (Hazard Ratio = 0.967, p = 0.009) alongside age and ELN risk. Conclusions: In conclusion, NRI outperforms other nutritional indices and serves as an independent prognostic factor in AML, offering a more holistic and effective approach to clinical risk stratification. Full article

Background and Objectives: The optimal role of postoperative radiotherapy and the prognostic factors influencing outcomes in patients with WHO grade 2 meningioma remain controversial. This study evaluated survival outcomes, local control, treatment-related toxicity, and prognostic factors in patients treated with postoperative radiotherapy. Materials and Methods: This retrospective single-center study included 50 consecutive adult patients with histologically confirmed WHO grade 2 meningioma who underwent surgical resection followed by radiotherapy between 2013 and 2024. Overall survival (OS) and local control (LC) were estimated using the Kaplan–Meier method, and median follow-up was calculated using the reverse Kaplan–Meier method. Univariable and multivariable Cox proportional hazards regression analyses were performed to identify prognostic factors associated with OS, while univariable analyses were performed for LC. Results: The reverse Kaplan–Meier median follow-up was 20.9 months (95% CI, 13.2–34.8). During follow-up, 10 patients died and 7 developed local recurrence. Median OS was 59.3 months (95% CI, 49.9 months–not estimable). The estimated 2- and 5-year OS rates were 85.0% and 44.8%, respectively, while the corresponding LC rates were both 76.2%. Increasing age and larger tumor size were independently associated with worse OS. All deaths and all local recurrences occurred in patients with postoperative residual disease. Acute adverse events were limited to Grade 1–2 toxicity, and no Grade ≥3 acute or late toxicities were observed. Conclusions: Postoperative radiotherapy achieved favorable local control with an acceptable safety profile in patients with WHO grade 2 meningioma. Postoperative residual disease was strongly associated with adverse clinical outcomes, while increasing age and larger tumor size were independently associated with worse overall survival. These findings support the importance of maximal safe resection, careful postoperative risk stratification, and individualized multidisciplinary treatment planning. Full article

Objectives: Functional tricuspid regurgitation (TR) recurrence after concomitant mitral–tricuspid surgery remains associated with adverse long-term outcomes, while reintervention on the isolated tricuspid valve carries substantial operative risk. Despite increasing awareness of the prognostic importance of functional TR, concomitant tricuspid valve repair remains inconsistently adopted in contemporary practice, particularly in technically demanding procedures. We sought to identify predictors of recurrent TR and develop an individualized prediction model to support patient-tailored surgical planning. Methods: This single-center ambispective study included 178 consecutive patients undergoing concomitant mitral–tricuspid surgery between January 2012 and June 2019. Baseline clinical, echocardiographic and operative variables were retrospectively collected, whereas long-term clinical and echocardiographic follow-up was prospectively completed after Ethics Committee approval. Clinical, echocardiographic and operative variables were first evaluated by univariable Cox proportional hazards analysis. Based on their univariable association with recurrent TR, biological plausibility and clinical relevance, candidate predictors were subsequently entered into a multivariable Cox proportional hazards model while limiting model complexity according to the number of available outcome events. Internal validation was performed by bootstrap resampling, and regression coefficients were transformed into an exploratory individualized perioperative nomogram estimating 5-year tricuspid regurgitation recurrence-free survival. Results: Univariable analysis identified female sex, dyslipidemia, left ventricular ejection fraction < 45%, severe pre-operative TR, indexed tricuspid annular diameter and suture-based annuloplasty as predictors of recurrent TR. Multivariable analysis identified surgical repair strategy as the only independent predictor associated with recurrent TR, with suture-based annuloplasty showing a significantly higher recurrence risk than prosthetic ring annuloplasty. These variables were integrated into an exploratory individualized prediction model estimating 5-year recurrence-free survival: the FuTURe nomogram. Conclusions: Our findings confirm the association between prosthetic ring annuloplasty and a lower risk of recurrent TR, consistent with current evidence supporting ring implantation as the preferred repair strategy. Beyond identifying predictors of recurrence, the FuTURe study proposes an exploratory perioperative individualized prediction model intended to complement current guideline recommendations. Consistent with its acronym, the FuTURe study shifts the focus from immediate procedural success to the patient’s future clinical trajectory, highlighting the value of individualized recurrence-risk assessment from a lifetime management perspective. Full article

Background and Objectives: During the 2016–2022 period, tyrosine kinase inhibitor (TKI) monotherapy was the standard first-line option at our center before combination protocols became available. This study evaluates patients experiencing initial TKI failure who subsequently received second- or later-line nivolumab. Because clinical practice lacks low-cost, accessible tools to prognosticate outcomes in this setting, we evaluated whether baseline psoas muscle index (PMI), early on-treatment C-reactive protein (CRP) kinetics, and a specific panel of blood-derived inflammatory/nutritional ratios offer reliable prognostic value. Materials and methods: We retrospectively reviewed data from 49 consecutive mRCC patients who progressed on a TKI and received second- or later-line nivolumab monotherapy. Primary endpoints were overall survival (OS; N = 49) and time-to-treatment failure (TTF; N = 48). We utilized Kaplan–Meier and Cox regression models for analysis. Benjamini–Hochberg false discovery rate (FDR) correction (q < 0.05) controlled false positive inflation across two separate testing frameworks: seven log-rank assessments for TTF and the core Cox models. Adjusted models accounted for clinical covariates including International Metastatic RCC Database Consortium (IMDC) risk category, Eastern Cooperative Oncology Group performance status (ECOG PS), and de novo metastatic presentation. We calculated the intraclass correlation coefficient (ICC) to evaluate measurement reproducibility. Results: Median follow-up reached 48.4 months (reverse Kaplan–Meier; maximum: 87.8 months), with a cohort-wide median OS of 13.9 months (IQR: 5.8–36.2). A low baseline C-reactive protein-to-albumin ratio (CAR) mapped to a distinct survival benefit, showing a median OS of 32.6 months versus 5.8 months in the high-CAR group (log-rank p < 0.001; BH q = 0.003). In adjusted multivariable Cox hazards modeling, both CAR (HR: 1.029; p = 0.002) and the prognostic nutritional index (PNI; HR: 0.893; p < 0.001) maintained independent prognostic significance. When evaluating the 43 patients with complete 3-month CRP records, we found a significantly higher objective response rate (ORR) in those at or below the cohort-median ratio threshold of 1.16 compared to patients above it (54.5% vs. 23.8%; p = 0.039). The overall ITT population registered an ORR of 36.7% (18/49). Conclusions: Low pretreatment CAR and elevated PNI identify mRCC patients showing improved survival profiles in this post-TKI nivolumab subgroup. Additionally, an elevated 3-month CRP ratio correlates with compromised objective response rates and a trend toward shorter TTF, though the TTF endpoint did not clear strict FDR parameters (BH q = 0.098). These retrospective, single-center data serve strictly for signal generation and require independent prospective multi-institutional confirmation before translating to oncology practice. Full article

Background/Objectives: Emergency presentation in colorectal cancer (CRC) is commonly regarded as a uniformly high-risk condition, although clinically distinct emergency phenotypes may carry substantially different prognostic implications. We aimed to characterise emergency diagnostic phenotypes, bowel obstruction, perforation, severe stenosis, and lower gastrointestinal bleeding, and to examine their associations with treatment allocation, perioperative mortality, and overall survival after adjustment for recorded covariates. Methods: We performed a retrospective, real-world cohort study of 1051 consecutive patients with CRC diagnosed between 2018 and 2021 at a tertiary referral centre. Patients were assigned to four mutually exclusive groups using a classification defined before outcome analysis (obstructive–perforative, stenotic, haemorrhagic, elective). Overall survival was assessed using Kaplan–Meier analysis and multivariable Cox regression, with formal testing of the proportional hazards assumption. Results: Emergency presentation occurred in 43.7% of patients but was markedly heterogeneous. Metastatic burden did not differ across phenotypes (p = 0.122). The obstructive–perforative phenotype showed the least favourable outcomes: perioperative mortality was 11.5%, and it remained associated with mortality after adjustment for recorded covariates (HR 1.58, 95% CI 1.25–2.00; p < 0.001), with hazard ratios ranging from 1.33 to 1.69 across six model specifications. Haemorrhagic presentation was rectal-predominant and behaved favourably, with survival comparable to elective diagnosis. Among 30-day survivors, the excess hazard was attenuated but persisted (HR 1.39, 95% CI 1.04–1.86). Conclusions: Emergency presentation in CRC is not a monolithic risk category. Recognising the presenting phenotype may offer a pragmatic framework for provisional risk characterisation at diagnosis, but external validation and adjustment for patient-level comorbidity and performance status are required before routine clinical use. Full article