Search Results (43)

Background/Objectives: Ventricular repolarization abnormalities (VRA) represent a grey area in athlete screening: some patterns are physiological, while others are precursors to heart disease. Objective: to clarify the natural history of VRA and the associated factors of structural diagnosis. Methods: Retrospective observational single-center study of athletes with resting or stress VRA at the first evaluation, with normal echocardiography; minimum follow-up of 2 years. Clinical data, resting and stress ECG, echocardiography, and selective advanced imaging throughout follow-up were collected. Primary outcome: cardiovascular diagnosis at follow-up; time-to-event analysis and associations between ECG characteristics and diagnosis. Results: Fifty-three athletes (mean age 22.2 ± 9.2 years; 92.5% male) were included; 60.4% had resting VRA, and 100% had exercise-induced VRA at baseline. Over 7.3 ± 4.5 years, 28/53 (52.8%) received a diagnosis; median time-to-detection was 7.0 years (95% CI 6.0–not reached); RMST10 was 6.7 years (95% CI 5.7–7.7). Diagnoses included hypertrophic cardiomyopathy (24.5%), non-ischaemic left-ventricular scar (11.3%), myocardial bridging (7.5%), hypertensive remodelling (5.7%), coronary anomaly (1.9%), and ventricular pre-excitation (1.9%). Persistence of resting VRA from baseline to follow-up was more frequent in athletes with a final diagnosis (p = 0.01), whereas topography and exercise-induced abnormalities did not discriminate groups. Advanced imaging contributed substantially to case ascertainment. No major adverse cardiovascular events have been identified throughout follow-up. Conclusions: In athletes with screening-detected VRA and normal echocardiography, persistence of resting VRA was associated with higher detection of a cardiovascular diagnosis, while exercise-induced changes alone show limited diagnostic yield. The long median time-to-detection supports prolonged, pre-planned surveillance, with priority for advanced imaging in profiles with persistent abnormalities. These findings align with a risk-adapted, personalized management strategy in sports cardiology. Full article

Background: After a failed endoscopic retrograde cholangiopancreatography (ERCP) for malignant biliary obstruction (MBO), second-line drainage is performed with endoscopic ultrasound-guided biliary drainage (EUS-BD) or percutaneous transhepatic biliary drainage (PTBD). We compared their effectiveness, safety, and short-term survival. Methods: We conducted a single-center retrospective cohort of 101 adults with MBO after they had experienced a failed ERCP (EUS-BD n = 37; PTBD n = 64). Allocation was non-randomized and driven by operational availability. Baseline laboratory tests (complete blood count, platelets, and C-reactive protein) and derived indices (neutrophil-to-lymphocyte ratio [NLR], platelet-to-lymphocyte ratio [PLR], lymphocyte-to-monocyte ratio [LMR], systemic immune-inflammation index [SII], systemic inflammation response index [SIRI], neutrophil-to-platelet score [NPS], and lymphocyte-to-CRP ratio [LCR]) were compared. Outcomes that were a technical success include: an early biochemical response (bilirubin reduction), complications (Clavien–Dindo), length of stay (LOS), and overall survival (OS). Between-group comparisons used the two-sided Mann–Whitney U test (continuous) and Fisher’s exact (binary) test. Survival was assessed by the Kaplan–Meier estimator using log-rank testing. To address later adoption of EUS-BD, we also estimated a restricted mean survival time of 180 days (RMST_0–180) with 95% confidence intervals (CIs). Results: Baseline inflammatory markers and composite indices were similar; baseline total bilirubin was higher in PTBD. The technical success was 100% in both groups. Early biochemical response was 86.5% after EUS-BD vs. 78.1% after PTBD (p = 0.43). Any complication occurred in 29.7% vs. 12.5% (p = 0.04); major complications (Clavien–Dindo ≥ III) occurred in 10.8% vs. 0% (p = 0.02), respectively; and the LOS did not differ (p = 0.21). OS favored EUS-BD (median 143 vs. 54 days and log-rank p = 0.012). RMST_0–180 was 111.1 days for EUS-BD vs. 71.4 days for PTBD (difference + 39.6 days; 95% CI 11.3–65.9). Conclusions: After a failed ERCP for MBO, EUS-BD and PTBD achieved universal technical success and similar early biochemical responses, but EUS-BD was associated with higher complication rates and a significantly longer six-month survival. These findings support the individualized selection balancing procedural risk with the anticipated survival benefit and highlight the need for prospective comparative studies. Full article

Background: Evidence on long-term visual field progression in childhood glaucoma compared with open-angle glaucoma (OAG) is limited. We compared the rate and timing of visual field progression and identified predictors of final visual field status. Methods: Single-center, retrospective, observational study including childhood glaucoma and OAG, with ≥3 reliable visual field tests and ≥2 years of follow-up. Visual fields were obtained with Octopus perimeter (Haag-Streit Diagnostics, Köniz, Switzerland) with the G grid and TOP strategy. Visual field progression was evaluated using the rate of change in mean defect (MD, dB/year). Rates were compared with the Mann–Whitney U test. Timing was evaluated with Kaplan–Meier and restricted mean survival time (RMST). Cox models assessed risk of progression. Secondary analysis used multiple linear regression to identify predictors of final MD. The mean follow-up duration was 5.7 ± 2.6 years. Results: 171 eyes (87 childhood glaucoma, 84 OAG) were analyzed. Childhood glaucoma had worse baseline MD (10.7 ± 7.5 dB) than OAG (5.1 ± 6.5 dB, p < 0.001), and underwent more surgeries, while OAG used more medications. The median MD progression rate was −2.3 dB/year [IQR: −5.6 to 0.1] in childhood glaucoma vs. 0.0 dB/year [IQR: −1.2 to 1.3] in OAG (p < 0.001), a value consistent with functional stability under treatment, with some eyes showing negative slopes indicating relative improvement. In Octopus perimetry, MD is expressed on a positive scale, so a negative slope reflects absence of visual field worsening, suggesting comparatively greater deterioration in OAG. Kaplan–Meier curves showed similar progression-free survival between groups (Log-Rank p = 0.284). RMST at 12 years was 10.93 years in childhood glaucoma and 10.56 years in OAG (difference ≈ 4.4 months, not clinically relevant). These survival results should be interpreted cautiously due to the low number of progression events and the high censoring rate. In regression, baseline MD was the strongest predictor of final MD; a higher number of medications was associated with worse final MD; number of surgeries and follow-up duration were not significant predictors. Conclusions: MD slopes suggested faster deterioration in OAG than in childhood glaucoma, whereas the timing to first progression was similar between groups. Baseline differences and treatment patterns were consistent with functional stability in childhood glaucoma under current management strategies. These findings support individualized follow-up and timely intervention, especially in pediatric patients. Full article

Recent evidence has highlighted the pivotal roles of reactive oxygen species (ROS) and the SIRT1, AMPK, and mTOR signaling pathways in aging and longevity, making them attractive targets for studies of lifespan-extending interventions. We previously demonstrated that 1,1-diethoxyethane (1,1-DEE) could interact with mitochondrial complex I (NADH–ubiquinone oxidoreductase), leading to transient mitochondrial ROS (mtROS) production and activation of the AMPK pathway. This study further examined the effects of 1,1-DEE on longevity in model organisms. Treatment with 1,1-DEE decreased senescence in endothelial cell EA.hy926. In Caenorhabditis elegans (C. elegans), 1,1-DEE induced a hormetic response and extended the lifespan, whereas its structural isoform, 1,2-diethoxyethane (1,2-DEE), showed no such effect. In rat models, administration of 1,1-DEE markedly improved survival rate, mortality risk, restricted mean survival time (RMST), and median lifespan, associated with an accelerated body weight reduction. Additionally, 1,1-DEE could also enhance learning and memory, as assessed by the Morris water maze test in rats. These findings suggest that 1,1-DEE may serve as a novel small-molecule modulator of mitochondrial function and redox signaling, with potentials for promoting anti-aging and longevity. Full article

Background and purpose: The role of adjuvant radiation therapy (RT) in early-stage HER2-positive breast cancer treated with breast-conserving surgery (BCS) and systemic therapy remains uncertain in the era of HER2-targeted regimens. This study evaluates the survival impact of RT in patients aligned with the HERO RT de-escalation trial (NRG-BR008). Materials and methods: We queried the National Cancer Database for patients with early-stage HER2-positive invasive breast carcinoma treated with BCS and systemic therapy, stratified into HERO trial-aligned cohorts: Arm 1 (adjuvant systemic therapy) vs. Arm 2 (neoadjuvant systemic therapy, pathologic complete response). Within each cohort, patients receiving adjuvant RT were compared with those omitting RT. In the primary analysis, patients were propensity score matched (PSM) on demographics, diagnosis years, tumor characteristics, and trial stratification variables. Inverse probability of treatment weighting (IPTW) was additionally performed as a sensitivity analysis. Overall survival was evaluated using Kaplan–Meier, Cox regression, and restricted mean survival time (RMST). Results: In Arm 1 (818 patients, 94 deaths), 5-year OS was 96.9% with RT vs. 88.0% without RT, and 10-year OS was 94.3% vs. 68.5% (log-rank p < 0.001). RT omission was associated with higher mortality in the PSM Cox model (HR, 4.78; 95% CI, 2.84–8.02; p < 0.001), with an RMST advantage favoring RT of +2.86 months at 5 years and +12.55 months at 10 years (p < 0.001). In Arm 2 (176 patients, 10 deaths), 5-year OS was 97.6% with RT vs. 91.1% without RT, and OS at 107 months was 94.8% vs. 91.1% (log-rank p = 0.13). RT omission was not statistically significant in the PSM Cox model (HR, 3.40; 95% CI, 0.82–14.05; p = 0.09), though RMST favored RT (+1.83 months at 5 years, p = 0.004; +3.91 months at 107 months, p = 0.03). IPTW analyses were directionally consistent in Arm 1 (HR, 3.26; 95% CI, 2.52–4.21; p < 0.001) and inconclusive in Arm 2 (HR, 1.78; 95% CI, 0.80–3.95; p = 0.16). Conclusions: In this HERO-aligned national cohort, RT omission was associated with inferior OS in patients treated with adjuvant systemic therapy after BCS. Findings in the neoadjuvant pCR cohort were imprecise and hypothesis-generating. Given the retrospective registry design, lack of recurrence-specific endpoints, and potential residual confounding, results should not be interpreted as causal but support continued RT use outside prospective de-escalation trials. Full article

Background: Glioblastoma (GB) carries a dismal prognosis, with survival outcomes particularly poor in older patients. With the fastest-growing global demographic being those aged over 65, the incidence of GB is expected to rise. Objective: To evaluate predictors of survival in patients aged ≥70 years with histologically confirmed GB, focusing on surgical resection, adjuvant therapy, and comorbidities. Methods: A retrospective review was performed of all patients aged ≥70 undergoing index surgery for GB between January 2021 and March 2025 at a single tertiary neurosurgical centre. Demographics, pre-operative fitness scores (Karnofsky Performance Status [KPS]., Charlson Comorbidity Index [CCI].), tumour characteristics, extent of resection, adjuvant treatment, and survival were analysed. Tumour volume was estimated using the ABC/2 method. Survival outcomes were assessed using Kaplan–Meier curves and multivariable Cox proportional hazards regression. Results: A total of 124 patients aged ≥70 years (median 74 years, range 70–86) were included. Median overall survival was 8 months (IQR 4–15). On multivariable analysis, adjuvant chemoradiotherapy (HR = 0.30, 95% CI 0.17–0.52; p < 0.001) and gross total resection (GTR) (HR = 0.41, 95% CI 0.20–0.86; p = 0.019) were independently associated with improved survival. Smoking history was associated with increased hazard of death (HR = 2.02, 95% CI 1.07–3.81; p = 0.029), an effect robust to multiple sensitivity analyses. No significant associations were found for age, pre-operative KPS, comorbidity index, tumour volume, or methylation status (all p > 0.10). Tests for non-proportional hazards indicated that the survival benefit of adjuvant therapy diminished over time (interaction p = 0.0002), with early post-operative benefit (HR ≈ 0.35 at 1 month) that attenuated towards unity by 6–12 months. The effects of GTR and smoking were time-invariant. RMST analysis suggested a modest, non-significant absolute survival advantage of GTR over STR (mean difference = 2.0 months at 18 months; p = 0.11). After exclusion of early post-operative deaths (<6 weeks), adjuvant therapy (HR = 0.34; p < 0.001) and GTR (HR = 0.33; p = 0.005) remained independent predictors of improved survival. Conclusions: Among patients aged ≥70 years with glioblastoma, adjuvant therapy and extent of resection remain key independent predictors of survival, while smoking is associated with poorer outcomes. The survival benefit of adjuvant chemoradiotherapy is strongest in the early post-operative period and diminishes over time, underscoring the importance of early multidisciplinary intervention. These findings highlight that aggressive multimodal treatment may confer survival advantage even in older patients. Full article

Chronic diseases, particularly those with progressive neurological impairment, present a significant challenge in healthcare due to their impact on millions globally and the limited availability of effective therapies. Addressing this challenge requires innovative approaches, such as leveraging individuals’ genetic features for early intervention and treatment strategies. Due to the irregular intervals of patient visits, clinical data typically appear as censored, necessitating advanced analytical methods. Thus, this study introduces GTsurvival, a novel network architecture that combines graph convolutional networks (GCN) with a neural decision tree, providing promising advancements in disease prediction. GTsurvival utilizes restricted mean survival time (RMST) as pseudo-observations and directly connects them with baseline variables. Through the joint simulation of RMST, GTsurvival can effectively utilize shared information and enhance its predictive ability for patients’ future survival status. Firstly, GTsurvival is introduced to handle complex censored data, emphasizing the crucial role of graphs utilized in GCNs for processing related information among samples. Secondly, the neural decision tree within GTsurvival enhances decision-making by mitigating uncertainty at split nodes, effectively minimizing the global loss function and optimizing survival analysis in high-dimensional datasets. Thirdly, evaluations on simulated datasets and a real-world neurodegenerative disease cohort verify that the proposed GTsurvival method surpasses existing approaches. This superiority is partly attributed to the inclusion of a generalized score test during feature selection, which helps capture variants associated with disease progression. Full article

Background/Objectives: The purpose of this study is to assess whether the addition of an oxymetazoline (OXY) hemostatic solution, which can be used to manage pulpal bleeding, maintains higher MTA survivability than pulpotomies treated with FS. Methods: In this retrospective cross-sectional study, patient data (n = 75) were used to assess radiographic and clinical signs and symptoms of pathosis in primary molars treated with a pulpotomy and a stainless-steel crown. Pulpotomies treated with FS (Group 1) were compared to those treated with MTA with OXY-induced hemostasis (Group 2). Restricted mean survival times (RMSTs) were calculated for the two groups, and Cox proportional hazards regression was used to analyze the effects of patient and practice level covariates on radiographic and clinical pathosis. Results: Cox proportional-hazard regression identified three potential covariates (age, pulpotomy groups, and procedure location) that predicted radiographic pathosis. The adjusted hazard ratio for Group 2 was 0.30 (95% CI: 0.11–0.82), indicating improved radiographic outcomes compared with Group 1 (p = 0.02). The 36-month RMST for Group 2 was 30.1 months (95% CI: 26.5–33.7) compared to 24.7 months (21.6–27.8) for Group 1 (p = 0.025). Conclusions: A pulpotomy utilizing OXY hemostasis prior to MTA placement led to a higher chance of pulpotomy survival than FS. Full article

Background/Objectives: This study explored the epidemiology of Status Epilepticus (SE) in Kazakhstan. Methods: Utilizing data from the National Health System from 2014 to 2023, we investigated the age-standardized incidence rate (ASIR) of SE. The authors employed restricted mean survival time (RMST) models to evaluate how sex, older age, epilepsy, history of cerebrovascular diseases (CVD), central nervous system (CNS) infections, brain tumors, and cancer affected survival during 30 days through the fifth year following hospital admission for SE. Results: This study included 14,010 patients. The ASIR per 100,000 increased threefold, from 4.15 (95% CI: 3.85; 4.46) in 2014 to 12.12 (95% CI: 11.64; 17.59) in 2023, with a sharp increase during the COVID-19 pandemic. The 30-day and 5-year mortality were 2.10% and 8.85%, respectively. The RMST identified that all-cause mortality was driven by elderly age, brain tumors, and cancer, where the difference in survival increased from one day at baseline to over a year by the fifth year. The effects of CVD, CNS infections, and sex on survival were substantially lower. However, epilepsy was associated with a better prognosis. Conclusions: We observed an incremental increase in the SE incidence over a decade. Our findings warrant actions to resolve issues related to rescue medicines to improve SE outcomes in both country and region. It may be a priority for elderly patients and those with systemic tumors. Further research is needed to understand the role of epilepsy in SE epidemiology, with emphasis on design-related biases. Full article

Background/Objectives: Acute Kidney Injury (AKI) requiring continuous renal replacement therapy (CRRT) has historically been a contraindication for left ventricular assist device (LVAD) implantation. However, advancements in magnetically levitated (MagLev) LVADs warrant reevaluation. Methods: A retrospective review of adult LVAD recipients at a tertiary center (2009–2024) was performed. Patients were stratified by preoperative CRRT status and LVAD type. Baseline characteristics and perioperative morbidity, Kaplan–Meier survival estimates, restrictive mean survival time (RMST), and Cox proportional hazards models were assessed. Results: Among 312 MagLev LVAD recipients, 22 (7.1%) required preoperative CRRT. Compared to non-CRRT patients, the CRRT group had higher illness severity (INTERMACS 1 or 2: 95% vs. 71%, p = 0.019). Despite this, preoperative CRRT was not associated with worse mortality within the MagLev cohort at 30 days (9.1% vs. 7.9%), 1 year (18.2% vs. 17.9%), or 2 years (31.8% vs. 20.7%; p = 0.31). RMST at 1 year was also similar (305 vs. 311 days; p = 0.85). In contrast, patients on CRRT receiving non-MagLev devices had significantly worse outcomes, with 30-day, 1-year, and 2-year mortality rates of 57.1%, 71.4%, and 78.6%, respectively. RMST analysis showed a 170-day survival advantage at 1 year for MagLev vs. non-MagLev CRRT patients (p < 0.01). Conclusions: In this single-center cohort, preoperative CRRT was not associated with higher mortality among MagLev LVAD recipients and may challenge traditional contraindications against LVAD therapy. Further investigations using larger cohorts are necessary to further evaluate these findings and delineate patient subgroups that may derive the greatest clinical benefit. Full article

Background: Cardiovascular disease (CVD) is a common cause of death among colorectal cancer (CRC) patients. We examined whether neighborhood disadvantage is associated with CVD mortality in CRC patients. Methods: Data were obtained from the Surveillance, Epidemiology, and End Results (SEER) program for primary CRC patients diagnosed between 2006 and 2017. Neighborhood disadvantage was measured using the quintiles of the Yost Index, a socioeconomic composite measure. Cause-specific mortality (CVD-specific and CRC-specific mortality) was evaluated using a competing risk cause-specific hazard model, controlling for demographic and clinical covariates. Cumulative incidence function (CIF) and restricted mean survival time (RMST) analyses were performed to provide complementary estimates of absolute risk and survival differences. Results: The study included 316,549 patients with CRC. Cancer-specific mortality was the leading cause of death (62.1%), while CVD accounted for 9.6% of deaths. Multivariable competing risk Cox regression showed that the lowest-SES neighborhoods (Group 1) had a higher CVD-specific mortality (HR, 1.39; 95% CI, 1.30–1.48; p < 0.001) compared to the highest-SES neighborhoods (Group 5). RMST and CIF analyses revealed a similar dose–response pattern, with progressively higher CVD mortality associated with increasing levels of neighborhood disadvantage. Effect modification analyses indicated stronger associations in older patients and men, but no modifications by race. Conclusions: Among CRC patients, residing in disadvantaged neighborhoods was independently associated with higher CVD mortality, suggesting the importance of addressing cardiovascular risk in disadvantaged populations. Full article

Background: Poly (ADP-ribose) polymerase inhibitors (PARPi) are the standard of care for first-line maintenance in advanced ovarian cancer, but their benefit varies by BRCA and homologous recombination deficiency (HRD) status, and no head-to-head comparisons are available. Methods: We conducted an indirect comparison of PARPi regimens using reconstructed individual patient data (IPD) from Kaplan–Meier curves of phase III randomized trials (SOLO1, PRIMA, PAOLA1, ATHENA, FLAMES). Progression-free survival (PFS) was the primary endpoint; overall survival (OS) was exploratory. Subgroups were defined as BRCA−mutated (BRCA+), BRCA−/HRD+, and BRCA−/HRD−. Safety outcomes were assessed through a network meta-analysis of adverse drug reactions (ADRs). Results: In BRCA+ patients, olaparib + bevacizumab achieved the largest PFS improvement (HR = 0.27; 95%CI: 0.19–0.39), followed by olaparib monotherapy, while niraparib performed significantly worse. In BRCA−/HRD+, olaparib + bevacizumab was superior to niraparib and rucaparib, with restricted mean survival time (RMST) gains of 3–4 months. In BRCA−/HRD−, PARPi produced only a modest benefit, with no advantage over bevacizumab monotherapy. Exploratory OS analysis confirmed long-term survival with olaparib in BRCA+ but not in the other subgroups. Safety analysis indicated olaparib had the most favorable hematological profile, while niraparib was associated with the highest rates of severe anemia, thrombocytopenia, and neutropenia, despite showing lower gastrointestinal toxicity and fatigue incidence. Conclusions: PARPi efficacy depends strongly on BRCA and HRD status. Olaparib-based regimens provide the greatest clinical benefit with acceptable safety in BRCA+ and HRD+ disease, whereas PARPi appear to be of limited value in HRD-negative ovarian cancer. Full article

Background: Multiple primary malignant tumors (MPMTs) involving the digestive tract pose diagnostic and therapeutic challenges, with survival differences between synchronous and metachronous forms not well defined. This study assessed predictors of overall survival (OS) in patients in whom at least one tumor originated in the digestive tract or accessory organs. Methods: We retrospectively reviewed 1920 oncology cases (January 2020–June 2023) from St. Nicholas Hospital, Romania. Of 118 patients with MPMTs, 45 had ≥1 digestive tract tumor. They were classified as synchronous (<2 months) or metachronous (>2 months) as per the SEER rules. Clinical, pathological, treatment, and follow-up data were analyzed; OS was evaluated using Kaplan–Meier and Cox regression. Results: Fifteen patients (33%) had synchronous tumors and 30 (67%) had metachronous tumors. Overall, 17 of 45 patients (37.8%) died by the last follow-up. The restricted mean survival time (RMST) was 31.3 months for those with synchronous vs. 68.3 months for those with metachronous tumors (HR = 2.49, 95% CI 0.95–6.50, p = 0.062; log-rank p = 0.053). Curative treatment of the first tumor was associated with markedly improved survival (RMST 58.2 vs. 29.4 months; HR = 20.5, 95% CI 3.68–114, p < 0.001). In the multivariable Cox regression analysis, advanced primary nodal stage (N2–N3) remained independently associated with reduced survival (adjusted HR 3.86, 95% CI 1.04–14.3, p = 0.044). The adjusted effect of synchronous vs. metachronous classification was attenuated (adjusted HR 2.22, 95% CI 0.84–5.86, p = 0.10). Conclusions: In this single-center, hypothesis-generating cohort, synchronous digestive-tract MPMTs were associated with shorter unadjusted survival than metachronous tumors, but advanced nodal stage and limited feasibility of curative therapy were the dominant independent predictors of poor outcome. Given the small sample size and retrospective design, these findings should be interpreted as preliminary and warrant validation in larger, multicenter cohorts. Full article

Background/Objectives: Results from a well-designed trial provide evidence to support approval of truly effective treatments or discontinuation of ineffective treatments. However, the information available at the time of trial design may be limited which may lead to underpowered trials. This work aims to evaluate the impact of design assumption misspecifications on the statistical power of randomized trials with survival outcomes. Methods: The impact of the design assumption misspecifications on statistical power of four different statistical methods was investigated in a simulation study. The methods include the log-rank test, MaxCombo test, the test of difference in survival probability, and test of difference in restricted mean survival time (RMST). The deviations considered include the survival rate in the control arm, the expected treatment effect in terms of magnitude and pattern, accrual rate, and drop-out rate. Results: Deviations in the control arm’s survival distribution have no impact on the power of the log-rank and MaxCombo tests but it affects the trial duration since trials designed with these tests require the total number of events to be met before the final analysis can be conducted. Misspecified treatment effect has similar effect on the statistical power of all four methods. When the proportional hazards assumption is misspecified, the RMST is more robust with a larger early treatment effect, while the survival probability and the MaxCombo tests are more robust with a larger late treatment effect and crossing hazards. Conclusions: Selecting the appropriate statistical tests to design a trial depends on the goal of the trial, the mechanism of action of the experimental treatment, the survival quantity of clinical interest, and the pattern of the expected treatment effect. The final design should be based on assumptions that are as accurate as possible, and the potential impacts of deviations from these assumptions on the trial’s statistical power should be carefully considered. Full article

Objectives: Chronic Hepatitis B virus (HBV) infection is a significant global health issue, with dialysis patients at increased risk and reduced response to HBV vaccination. The effects of HBV serological status on kidney transplant outcomes, particularly for patients with resolved or inactive HBV infection, needs more data, especially from current era. This study evaluated the impact of chronic and non-active HBV infection on patient and graft survival after kidney transplantation. Methods: Retrospective analysis was conducted of kidney-only transplant recipients at our center from 1 January 1990 to 31 August 2019 (end of observation). Patients were grouped by their HBV serostatus before transplantation into three categories: HBV negative (HBsAg−/Anti-Hbc−), non-active HBV infection (HbsAg−/Anti-Hbc+) and chronic HBV infection (HbsAg+/Anti-Hbc+). Primary outcomes included patient survival, graft survival, and overall graft and patient survival, analyzed using Kaplan–Meier (KM) curves, log-rank tests, Restricted mean survival times (RMST), and Accelerated failure time (AFT) models. Results: Among 2490 patients, 2197 were HBV negative, 218 had non-active HBV, and 75 had chronic HBV. Over a mean follow-up of 8.1 years, mortality and graft failure rates were highest in chronic HBV patients (49% and 37%), followed by non-active HBV (39% and 29%) and HBV-negative patients (30% and 20%). KM analysis revealed significantly lower overall survival rates for chronic HBV and non-active HBV groups compared to HBV-negative patients (p = 0.006). RMST confirmed significant reductions in survival for the non-active group (12.57 vs. 14.17 years, p = 0.007). Cox regression and AFT models identified older recipient/donor age, Hepatitis-C-virus coinfection, and broad antigen mismatches as negative predictors, while living donors improved outcomes. Conclusions: While unadjusted Kaplan–Meier curves and RMST analysis suggested differences in patient and graft survival, further thorough multivariable AFT analysis did not show a significant association between non-active or chronic HBV infection and patient or graft survival after kidney transplantation. Full article