Competing Risk Analysis Research Articles

Mortality follow-up of Fernald Feed Materials Production Center workers exposed to uranium from 1951 to 1985

ObjectiveThis follow-up study of uranium processing workers at the Fernald Feed Materials Production Center examines the relationship between radiation exposure and cancer and non-cancer mortality among 6403 workers employed for...

Association between complementary use of Goreisan (a Japanese herbal Kampo medicine) and heart failure readmission: A nationwide propensity score-matched study

BackgroundGoreisan, a Japanese herbal medicine, possesses aquaretic properties to regulate body fluid homeostasis and may therefore be effective as a complement to standard therapy in improving outcomes in patients with heart failure (HF). MethodsWe retrospectively identified 431,393 patients (mean age 79.2 ± 12.6 years; male 52.3 %) who were admitted for HF for the first time and were discharged alive with standard HF medications between April 2016 and March 2022, using the Japanese Diagnosis Procedure Combination database. We divided patients into two groups according to the prescription of Goreisan at discharge: patients who received standard HF medications plus Goreisan and those who received standard medications alone. We compared the incidence of HF readmission within 1 year after discharge between the groups using propensity score matching. ResultsOverall, Goreisan was prescribed in 1957 (0.45 %) patients at discharge. Patients who received Goreisan were older and received diuretics more frequently than those who did not. One-to-four propensity score matching created a cohort of 1957 and 7828 patients treated with and without Goreisan, respectively. No significant difference was found in the incidence of 1-year HF readmission between the groups [22.1 % vs. 21.7 %; hazard ratio (HR) = 1.02, 95 % confidence interval (CI) = 0.92–1.13]. This result was consistent with that from competing risk analysis (subdistribution HR = 1.02, 95 % CI = 0.92–1.13) and across clinically relevant subgroups except for renal disease. Goreisan use was associated with a lower incidence of HF readmission among patients with renal disease (HR = 0.77, 95 % CI = 0.60–0.97), but not among those without (HR = 1.09, 95 % CI = 0.97–1.23; p for interaction = 0.009). ConclusionsThis nationwide propensity score-matched analysis did not demonstrate that complementary Goreisan use at discharge was associated with a lower incidence of 1-year HF readmission in patients with HF receiving standard medications. An ongoing randomized trial is awaited to establish the effectiveness of Goreisan use in patients with HF.

Impact of the grade and jet-flow direction of residual aortic regurgitation after valve-sparing root replacement

ObjectivesTo investigate the impact of the grade and jet direction of residual aortic regurgitation (rAR) after valve-sparing root replacement (VSRR). MethodsThe study enrolled 248 adult patients who underwent VSRR between 1995 and 2021. The patients were divided into groups based on the postoperative rAR. Patients with rAR were further categorized according to rAR grade and jet direction. The primary endpoint was the development of aortic regurgitation of moderate or greater (≥moderate) severity and/or the need for valve replacement during the follow-up, analyzed by a multivariable competing risk analysis. The secondary endpoints included the occurrence of rAR and overall survival. ResultsThe median age of the patients was 36.5 years, and 79.8% had been diagnosed with connective tissue disease. After VSRR, 146 patients did not present with rAR; however, 102 had rAR (77 with minimal central, 18 with minimal eccentric, and 7 with mild rAR). The 5-year and 8-year incidence rates of the primary endpoint were 14.6% and 17.9%, respectively. rAR was a significant risk factor (P = .001), and eccentricity and mild rAR seemed to have important roles. The risk factors for rAR included dilated root, preoperative moderate regurgitation, and redo sternotomy. Overall survival was influenced only by age. ConclusionsrAR after VSRR operation could be a risk factor for AR progression. Minimal central rAR generally has a tolerable clinical course; however, patients with even minimal eccentric AR may develop AR progression, so active surveillance and timely management might be required. Furthermore, early VSRR can help reduce the rAR.

A nomogram to predict cancer-specific mortality in adult patients with malignant meningioma: a competing risk analysis

BackgroundComprehensive investigations of the prognosis factors and treatment strategies with adjustment of competing causes of death for patients with malignant meningioma (MM) is still lacking.Patient and methodThe surveillance, Epidemiology, and End Results (SEER) database were used to include adult patients with this rare disease between 2004 and 2018. The probability of MM-caused mortality (MMCM) and non-MM-caused mortality (non-MMCM) were presented by cumulative incidence function curves. Then, the association between variates with non-MMCM was evaluated by the cox proportional hazard model, and the prognostic factors of MMCM were identified by Fine-Gray competing risk regression model. Furthermore, a nomogram was developed to predict the 1-year, 2-year, and 5-year MMCM and the performance was tested by a time-dependent area under the receiver operating characteristic (ROC) curve and calibration.Result577 patients were included, with a median age of 62 (18–100) years old and a median overall survival time of 36 (0–176) months. The percentage of non-MMCM was 15.4% (n = 89) in the entire population and 21.7% (n = 54) in elderly patients. The multivariable Cox proportional hazard regression model revealed that older age and other tumor(s) before or after MM had an independently significant association with higher non-MMCM. After adjustment of competing causes of death, the multivariable Fine-gray regression model identified age group ≥ 65 year, tumor size > 5.3 cm, recurrent MM, and histologic type 9530/3 (Meningioma, malignant) had an independently significant association with higher MMCM. Compared with gross total (GTR) of tumor, subtotal resection of tumor (HR 1.66, 95%CI 1.08–2.56, P = 0.02), partial resection of lobe (HR 2.26, 95%CI 1.32–3.87, P = 0.003), and gross total resection of lobe (HR 1.69, 95%CI 1.12–2.51, P = 0.01) had an independently significant association with higher MMCM.ConclusionThe competing risk nomogram including age group, tumor size, initial status, histologic type, and extent of resection is discriminative and clinically useful. This study emphasized the importance of the GTR of tumor in the treatment of MM patients, which had a significantly lower incidence of MMCM compared with biopsy, STR of tumor, partial resection of lobe, and GTR of lobe.

Influence of design features and brand of reverse shoulder arthroplasties on survivorship and reasons for revision surgery: results of 5,494 arthroplasties with up to 15 years' follow-up reported to the Norwegian Arthroplasty Register 2007-2022.

We aimed to report the survival of different reverse shoulder arthroplasty (RSA) designs and brands, and factors associated with revision. The secondary aim was to evaluate the reasons for revision. We included 4,696 inlay and 798 onlay RSAs reported to the Norwegian Arthroplasty Register (NAR) 2007-2022. Kaplan-Meier estimates of survivorship and Cox models adjusted for age, sex, diagnosis, implant design, humeral fixation, and previous surgery were investigated to assess revision risks. The reasons for revision were compared using competing risk analysis. Overall, the 10-year survival rate was 94% (confidence interval [CI] 93-95). At 5 years all brands exceeded 90%. Compared with Delta Xtend (n = 3,865), Aequalis Ascend Flex (HR 2.8, CI 1.7-4.6), Aequalis Reversed II (HR 2.2, CI 1.2-4.2), SMR (HR 2.5, CI 1.3-4.7), and Promos (HR 2.2, CI 1.0-4.9) had increased risk of revision. Onlay and inlay RSAs had similar risk of revision (HR 1.2, CI 0.8-1.8). Instability and deep infection were the most frequent revision causes. Male sex (HR 2.3, CI 1.7-3.1), fracture sequelae (HR 3.1, CI 2.1-5.0), and fractures operated on with uncemented humeral stems had increased risk of revision (HR 3.5, CI 1.6-7.3). We found similar risk of revision with inlay and onlay designs. Some prosthesis brands had a higher rate of revision than the most common implant, but numbers were low.

Effect of transjugular intrahepatic portosystemic shunt insertion on waitlist mortality and access to liver transplantation in budd-chiari syndrome.

The impact of transjugular intrahepatic portosystemic shunt (TIPS) on waitlist mortality and liver transplantation (LT) urgency in Budd-Chiari Syndrome (BCS) patients remains unclear. We analyzed BCS patients listed for LT in the UNOS database(2002-2024) to assess TIPS's impact on waitlist mortality and LT access via competing-risk analysis. We compared trends across two phases:Phase1(2002-2011) and Phase2(2012-2024). Of 815 BCS patients, 263(32.3%) received TIPS at listing. TIPS group had lower MELD-Na scores(20vs22,p<0.01), milder ascites(p=0.01), and fewer Status1 patients(those at risk of imminent death while awaiting LT)(2.7%vs8.3%,p<0.01) at listing compared to those without TIPS. TIPS patients had lower LT rates(43.3%vs56.5%,p<0.01) and longer waitlist times(350vs113d,p<0.01). TIPS use increased in Phase2(64.3%vs35.7%,p<0.01). Of 426 transplanted patients, 134(31.5%) received TIPS, showing lower MELD-Na scores(24vs27,p<0.01) and better medical conditions(Intensive care unit:14.9%vs21.9%,p<0.01) at LT. Status1 patients were fewer (3.7%vs12.3%,p<0.01), with longer waiting days(97vs26d,p<0.01) in TIPS group. TIPS use at listing increased from Phase1(25.6%) to Phase2(37.7%). From Phase1 to Phase2, ascites severity improved, re-LT cases decreased(Phase1:9.8%vsPhase2:2.2%,p<0.01), and cold ischemic time slightly decreased(Phase1:7.0vsPhase2:6.4 hours,p=0.14). Median donor body mass index significantly increased. No significant differences were identified in patient/graft survival at 1-/5-/10-year intervals between phases or TIPS/non-TIPS patients. While 90-day waitlist mortality showed no significant difference(p=0.11), TIPS trended towards lower mortality(subHazard ratio[sHR]:0.70[0.45-1.08]). Multivariable analysis indicated that TIPS was a significant factor in decreasing mortality(sHR:0.45[0.27-0.77],p<0.01). TIPS group also showed significantly lower LT access(sHR:0.65[0.53-0.81],p<0.01). Multivariable analysis showed that TIPS was a significant factor in decreasing access to LT(sHR:0.60[0.46-0.77],p<0.01). Sub-group analysis excluding Status1 or HCC showed similar trends. TIPS in BCS patients listed for LT reduces waitlist mortality and LT access, supporting its bridging role.

Investigating the Obesity Paradox in Colorectal Cancer: An Analysis of Prospectively Collected Data in a Diverse Cohort.

Prior studies are inconclusive regarding the effect of obesity on mortality in persons with colorectal cancer (CRC). We sought to determine the association of pre-diagnosis body mass index (BMI) trajectories on mortality after CRC diagnosis. Utilizing the Multiethnic Cohort, we included adults aged 18-75 between 1 January 1993 and 1 January 2019 with a diagnosis of CRC and at least three available BMIs. The primary exposure, BMI, was subjected to group-based trajectory modeling (GBTM). We evaluated all-cause and CRC-specific mortality, using Cox proportional hazard (PH) models. Of 924 persons, the median age was 60 years, and 54% were female. There was no statistically significant association between pre-cancer BMI trajectory and either all-cause or cancer-specific mortality. In competing risk analysis, the risk of CRC-specific mortality was higher for African Americans (HR = 1.56, 95% CI [1.00-2.43], p = 0.048) and smokers (HR = 1.59, 95% CI [1.10-2.32], p = 0.015). Risk of all-cause mortality was higher for Hawaiian persons (HR = 2.85, 95% CI [1.31-6.21], p = 0.009) and persons with diabetes (HR = 1.83, 95% CI [1.08-3.10], p = 0.026). Pre-diagnosis BMI trajectories were not associated with mortality after CRC diagnosis, whereas race/ethnicity, diabetes, and smoking were associated with an increased risk of death. Our findings suggest the obesity paradox alone does not account for mortality after CRC diagnosis.

Reappraisal of tacrolimus levels after liver transplant for HCC: A multicenter study toward personalized immunosuppression regimen.

Post-liver transplant (LT) immunosuppression is necessary to prevent rejection; however, a major consequence of this is tumor recurrence. Although recurrence is a concern after LT for patients with HCC, the oncologically optimal tacrolimus (FK) regimen is still unknown. This retrospective study included 1406 patients with HCC who underwent LT (2002-2019) at 4 US institutions using variable post-LT immunosuppression regimens. Receiver operating characteristic analyses were performed to investigate the influences of post-LT time-weighted average FK (TWA-FK) level on HCC recurrence. A competing risk analysis was employed to evaluate the prognostic influence of TWA-FK while adjusting for patient and tumor characteristics. The AUC for TWA-FK was greatest at 2 weeks (0.68), followed by 1 week (0.64) after LT. Importantly, this was consistently observed across the institutions despite immunosuppression regimen variability. In addition, the TWA-FK at 2 weeks was not associated with rejection within 6 months of LT. A competing risk regression analysis showed that TWA-FK at 2 weeks after LT is significantly associated with recurrence (HR: 1.31, 95% CI: 1.21-1.41, p < 0.001). The TWA-FK effect on recurrence varied depending on the exposure level and the individual's risk of recurrence, including vascular invasion and tumor morphology. Although previous studies have explored the influence of FK levels at 1-3 months after LT on HCC recurrence, this current study suggests that earlier time points and exposure levels must be evaluated. Each patient's oncological risk must also be considered in developing an individualized immunosuppression regimen.

Individual-level social determinants of health and disparities in access to kidney transplant and waitlist mortality.

Comprehensive, individual-level social determinants of health (SDOH) are not collected in national transplant registries, limiting research aimed at understanding the relationship between SDOH and waitlist outcomes among kidney transplant candidates. We merged Organ Procurement and Transplantation Network data with individual-level SDOH data from LexisNexis, a commercial data vendor, and conducted a competing risk analysis to determine the association between individual-level SDOH and the cumulative incidence of living donor kidney transplant (LDKT), deceased donor kidney transplant (DDKT), and waitlist mortality. We included adult kidney transplant candidates placed on the waiting list in 2020, followed through December 2023. In multivariable analysis, having public insurance (Medicare or Medicaid), less than a college degree, and any type of derogatory record (liens, history of eviction, bankruptcy and/ felonies) were associated with lower likelihood of LDKT. Compared with patients with estimated individual annual incomes ≤ $30,000, patients with incomes ≥ $120,000 were more likely to receive a LDKT (sub distribution hazard ratio (sHR), 2.52; 95% confidence interval (CI), 2.03-3.12). Being on Medicare (sHR, 1.49; 95% CI, 1.42-1.57), having some college or technical school, or at most a high school diploma were associated with a higher likelihood of DDKT. Compared with patients with incomes ≤ $30,000, patients with incomes ≥ $120,000 were less likely to receive a DDKT (sHR, 0.60; 95% CI, 0.51-0.71). Lower individual annual income, having public insurance, at most a high school diploma, and a record of liens or eviction were associated with higher waitlist mortality. Patients with adverse individual-level SDOH were less likely to receive LDKT, more likely to receive DDKT, and had higher risk of waitlist mortality. Differential relationships between SDOH, access to LDKT, DDKT, and waitlist mortality suggest the need for targeted interventions aimed at decreasing waitlist mortality and increasing access to LDKT among patients with adverse SDOH.

The role of marital status in gallbladder cancer: a real-world competing risk analysis

BackgroundThe association between marital status and gallbladder cancer (GBC) remains uncertain. This study aimed to verify the relationship between marital status and GBC and construct a prognostic nomogram to predict the impact of marital status on GBC patients.MethodGBC patients were divided into married and unmarried groups using data from the Surveillance, Epidemiology, and End Results (SEER) database. We employed competing risk analyses, propensity score matching (PSM), and Kaplan-Meier survival analyses. The relationship between marital status and GBC was then verified, and the predicted nomogram was constructed.ResultsA total of 3913 GBC patients were obtained from the SEER database, and an additional 76 GBC patients from Hangzhou Traditional Chinese Medicine Hospital were selected as the external validation group. The competing risk analysis revealed a significant disparity in the 5-year cumulative incidence of cancer-specific death (CSD) between the two cohorts (59.1% vs. 65.2%, p = 0.003). Furthermore, the multivariate competing hazards regression analysis identified a significant association (HR, 1.17; 95% CI, 1.04–1.31; p = 0.007) between marital status and CSD. To assess the 1-, 3-, and 5-year risks of CSD, a comprehensive competing event nomogram was constructed using factors derived from the multivariate analysis. The area under the receiver operating characteristic curve (AUC) values for the 1-, 3-, and 5-year training cohorts were 0.806, 0.785, and 0.776, respectively. In the internal validation cohort, these values were 0.798, 0.790, and 0.790, while the external validation cohort exhibited AUC values of 0.748, 0.835, and 0.883 for the corresponding time intervals. Furthermore, calibration curves demonstrated a commendable level of concordance between the observed and predicted probabilities of CSD.ConclusionMarriage was a protective factor for GBC patients after taking competing risk into consideration. The proposed nomogram demonstrated exceptional predictive power.

Post-Kidney Transplant Cancer: A Real-World Retrospective Analysis From a Single Italian Center.

We describe the epidemiology of cancer after kidney transplantation (KTx), investigating its risk factors and impact on therapeutic management and survival in KTx recipients (KTRs). The association between modification of immunosuppressive (IS) therapy after cancer and survival outcomes was analyzed. We collected data from 930 KTRs followed for 7 [1-19]years. The majority of KTRs received KTx from a deceased donor (84%). In total, 74% of patients received induction therapy with basiliximab and 26% with ATG. Maintenance therapy included steroids, calcineurin inhibitors, and mycophenolate. Patients with at least one cancer (CA+) amounted to 19%. NMSC was the most common tumor (55%). CA+ were older and had a higher BMI. Vasculitis and ADPKD were more prevalent in CA+. ATG was independently associated with CA+ and was related to earlier cancer development in survival and competing risk analyses (p = 0.01 and <0.0001; basiliximab 89 ± 4 vs. ATG 40 ± 4months). After cancer diagnosis, a significant prognostic impact was derived from the shift to mTOR inhibitors compared to a definitive IS drug suspension (p = 0.004). Our data confirm the relevance of cancer as a complication in KTRs with ATG as an independent risk factor. An individualized choice of IS to be proposed at the time of KTx is crucial in the prevention of neoplastic risk. Finally, switching to mTORi could represent an important strategy to improve patient survival.

Remote monitoring of automated peritoneal dialysis reduces mortality, adverse events, and hospitalizations: a cluster randomized controlled trial.

Remote monitoring (RM) of patients on automated peritoneal dialysis (APD) prevent complications and improve treatment quality. We analyzed the effect of RM-APD on mortality and complications related to cardiovascular disease (VD), fluid overload and insufficient dialysis efficiency. In a cluster-randomized, open-label, controlled trial, 21 hospitals with APD programs were assigned to use either RM-APD (10 hospitals; 403 patients) or conventional APD (11 hospitals; 398 patients) for the treatment of adult patients starting PD. Primary outcomes were time to first event of: 1) Composite Index-1 comprising all-cause mortality, first adverse events and hospitalizations of any cause, and 2) Composite Index-2 comprising cardiovascular mortality, first adverse event and hospitalizations related to CVD, fluid overload and insufficient dialysis efficiency. Secondary outcomes were time to first event of individual components of the two composite indices, and rates of adverse events, hospitalizations, unplanned visits, and transfer to hemodialysis. Patients were followed for a median of 9.5 months. Primary outcomes were evaluated by competing-risk analysis and restricted mean survival time (RMST) analysis. While time to reach Composite Index-1 did not differ between the groups, Composite Index-2 was reached earlier (ΔRMST: -0.85 months; p=0.02), and all-cause mortality (55 vs. 33 deaths, p=0.01; sHR 1.69 (95%CI 1.39-2.05), p<0.001) and hospitalizations of any cause were higher in APD group than in RM-APD as were cardiovascular deaths (24 vs. 13 deaths, p=0.05; sHR 2.44 (95%CI 1.72 - 3.45), p<0.001) and rates of adverse events and hospitalizations related to CVD, fluid overload or insufficient dialysis efficiency. Dropouts were more common in the APD group (131 vs. 110, p=0.048). This randomized controlled trial shows that remote monitoring may add significant advantages to APD, including improved survival and reduced rate of adverse events and hospitalizations, which can favorably impact the acceptance and adoption of the therapy.

Surrogates of Endothelial Injury Predict Survival After Post-transplant Cyclophosphamide

Post-transplant cyclophosphamide (PT-Cy) is becoming the standard of care for preventing graft-versus-host disease (GVHD) following allogeneic hematopoietic stem cell transplant (alloHCT). Cyclophosphamide is associated with endothelial injury. We hypothesized that the endothelial activation and stress index (EASIX) score, being a marker of endothelial dysfunction, will predict non-relapse mortality (NRM) in alloHCT patients receiving PT-Cy for GVHD prophylaxis. We evaluate the prognostic ability of the hematopoietic cell transplantation-specific comorbidity index (HCT-CI) and EASIX scores, and report other factors influencing survival, in patients with hematologic malignancies undergoing alloHCT and receiving PT-Cy-based GVHD prophylaxis. Adult patients with hematologic malignancies who underwent alloHCT and received PT-Cy for GVHD prophylaxis at the three Mayo Clinic locations were included in this study. We retrospectively reviewed the Mayo Clinic database and the available electronic medical records to determine the patient, disease, and transplant characteristics. An HCT-CI score of ≥3 was considered high. The EASIX score was calculated from labs available between day -28 (of alloHCT) to the day of starting conditioning and analyzed on log2 transformed values. A log2-EASIX score ≥2.32 was considered high. The cumulative incidence of NRM was determined using competing risk analysis, with relapse considered as competing risk. Overall survival (OS) from transplant was determined using Kaplan-Meier and log-rank methods. Cox-proportional hazard method was used to evaluate factors impacting survival. A total of 199 patients were evaluated. Patients with a high log2-EASIX score had a significantly higher cumulative incidence of NRM at 1 year after alloHCT (34.5% versus 12.3%, P = .003). Competing risk analysis showed that a high log2-EASIX score (HR 2.92, 95% CI 1.38 to 6.17, P = .005) and pre-alloHCT hypertension (HR 2.15, 95% CI 1.06 to 4.36, P = .034) were independently predictive of 1 year-NRM. Accordingly, we combined the two factors to develop a composite risk model stratifying patients in low, intermediate, and high-risk groups: 111 (55.8%) patients were considered low-risk, 76 (38.2%) were intermediate and 12 (6%) were high-risk. Compared to patients in the low-risk group, the intermediate (HR 2.38, 95% CI 1.31 to 4.33, P = .005) and high-risk (HR 5.77, 95% CI 2.31 to 14.39, P < .001) groups were associated with a significantly inferior 1-year OS. Multiorgan failure (MOF) was among the common causes of NRM (14/32, 43.8%) particularly among patients with prior pulmonary comorbidities [7 (50%) patients]. Our study shows that EASIX score is predictive of survival after PT-Cy. The novel EASIX-HTN composite risk model may stratify patients prior to transplant. MOF is a common cause of NRM in patients receiving PT-Cy, particularly among patients with pulmonary comorbidities.

Associations of CD4 Cell Count Measures With Infection-Related and Infection-Unrelated Cancer Risk Among People With HIV.

People with HIV are at higher risk of infection-related cancers than the general population, which could be due, in part, to immune dysfunction. Our objective was to examine associations between 4 CD4 count measures as indicators of immune function and infection-related and infection-unrelated cancer risk. We conducted a cohort study of adults with HIV who were diagnosed with cancer in Ontario, Canada. Incident cancers were identified from January 1, 1997 to December 31, 2020. We estimated adjusted hazard ratios (aHR) for the associations between CD4 measures (baseline CD4, nadir CD4, time-updated CD4, time-updated CD4:CD8) and cancer incidence rates using competing risk analyses, adjusted for socio-demographic factors, history of hepatitis B or C infection, baseline viral load, smoking, and alcohol use. Among 4771 people with HIV, contributing 59,111 person-years of observation, a total of 549 cancers were observed. Low baseline CD4 (<200 cells/µL) (aHR 2.08 [95% CI: 1.38 to 3.13], nadir (<200 cells/µL) (aHR 2.01 [95% CI: 1.49 to 2.71]), low time-updated CD4 (aHR 3.52 [95% CI: 2.36 to 5.24]) and time-updated CD4:CD8 ratio (<0.4) (aHR 2.02 [95% CI: 1.08 to 3.79]) were associated with an increased rate of infection-related cancer. No associations were observed for infection-unrelated cancers. Low CD4 counts and indices were associated with increased rates of infection-related cancers among people with HIV, irrespective of the CD4 measure used. Early diagnosis and linkage to care and high antiretroviral therapy uptake may lead to improved immune function and could add to cancer prevention strategies such as screening and vaccine uptake.

The Impact of Radical Prostatectomy Versus Radiation Therapy on Cancer-Specific Mortality for Nonmetastatic Prostate Cancer: Analysis of an Other-Cause Mortality Matched Cohort

IntroductionStudies comparing radical prostatectomy (RP) to radiation therapy (RT) have consistently shown that patients undergoing RT have a higher risk of other-cause mortality (OCM) compared to RP, signifying poor health status of the former patients. We aimed to evaluate the impact of RP versus RT on cancer-specific mortality (CSM) over a cohort with equivalent OCM risk. Patients and MethodsThe SEER database was queried to identify patients with nonmetastatic PCa between 2004 and 2009. Patients were matched based on their calculated 10-year OCM risk and further stratified for D'Amico Risk Score and Gleason Grade. A Cox-regression model was used to calculate the 10-year OCM risk. Propensity-score based on the calculated OCM risk were used to match RP and RT patients. Cumulative incidence curves and Competing-risk regression analyses were used to examine the impact of treatment on CSM in the matched cohort. ResultsWe identified 55,106 PCa patients treated with RP and 36,674 treated with RT. After match, 6,506 patients were equally distributed for RT versus RP, with no difference in OCM rates (P = .2). The 10-year CSM rates were 8.8% versus 0.6% (P = .01) for RT versus RP in patients with unfavorable-intermediate-risk (Gleason Score 4 + 3) and 7.9% versus 3.9% (P = .003) for high-risk disease. There was no difference in CSM among RT and RP patients for favorable-intermediate-risk (Gleason Score 3 + 4) and low-risk disease. ConclusionsIn a matched cohort of PCa patients with comparable OCM between the 2 arms, RP yielded a more favorable CSM rate compared to RT only for unfavorable-intermediate- and high-risk groups.

Recurrences after nephron-sparing treatments of renal cell carcinoma: a competing risk analysis

PurposeTo examine associations between ablative therapy (AT) and partial nephrectomy (PN) and the occurrence of local recurrence (LR), distant metastatic recurrence (DMR) and all-cause mortality in a nation-wide real-world population-based cohort of patients with nonmetastatic renal cell carcinoma (nmRCC).MethodsData on 2751 AT- or PN-treated nmRCC tumours diagnosed during 2005–2018, representing 2701 unique patients, were obtained from the National Swedish Kidney Cancer Register. Time to LR/DMR or death with/without LR/DMR was analysed using Cox regression models.ResultsDuring a mean of 4.8 years follow-up, LR was observed for 111 (4.0%) tumours, DMR for 108 (3.9%) tumours, and death without LR/DMR for 206 (7.5%) tumours. AT-treated tumours had a 4.31 times higher risk of LR (P < 0.001) and a 1.91 times higher risk of DMR (P = 0.018) than PN-treated, with no significant differences in risk of death without LR/DMR. During a mean of 3.2 and 2.5 years of follow-up after LR/DMR, respectively, 24 (21.6%) of the LR cases and 56 (51.9%) of the DMR cases died, compared to 7.5% in patients without LR/DMR. There were no significant differences between AT- and PN-treated regarding risks of early death after occurrence of LR or DMR.ConclusionAT treatment of patients with nmRCC implied significantly higher risks of LR and DMR compared with PN treatment. To minimize the risks of LR and DMR, these results suggest that PN is preferred over AT as primary treatment, supporting the EAU guidelines to recommended AT mainly to frail and/or comorbid patients.

The non-high-density lipoprotein cholesterol to high-density lipoprotein cholesterol ratio (NHHR) as a predictor of all-cause and cardiovascular mortality in US adults with diabetes or prediabetes: NHANES 1999–2018

BackgroundThe non-high-density lipoprotein cholesterol to high-density lipoprotein cholesterol ratio (NHHR) serves as a novel composite lipid indicator for atherosclerosis. However, the association between NHHR and mortality in patients with diabetes or prediabetes remains unclear. Consequently, the objective of this study was to investigate the relationship between NHHR and both all-cause and cardiovascular mortality in US adults with diabetes or prediabetes.MethodsThis study included 12,578 adult participants with diabetes or prediabetes from the US National Health and Nutrition Examination Survey (1999–2018). Mortality outcomes were ascertained by linking to the National Death Index (NDI) record up to December 31, 2019. We employed a weighted multivariate Cox proportional hazards model and restricted cubic splines to assess the associations between NHHR and all-cause and cardiovascular mortality. A segmented Cox proportional hazards model was used for evaluating threshold effects. Furthermore, a competing risks analysis was performed to explore the relationship between NHHR and cardiovascular mortality.ResultsDuring a median follow-up period of 8.08 years, 2403 participants encountered all-cause mortality, with 662 of them specifically succumbing to cardiovascular mortality. The restricted cubic splines revealed a U-shaped association between NHHR and all-cause mortality, while an L-shaped association was observed for cardiovascular mortality. The analysis of threshold effects revealed that the inflection points for NHHR and all-cause and cardiovascular mortality were 2.72 and 2.83, respectively. Specifically, when the baseline NHHR was below the inflection points, a negative correlation was observed between NHHR and both all-cause mortality (HR: 0.76, 95% CI: 0.68–0.85) and cardiovascular mortality (HR: 0.70, 95% CI: 0.57–0.85). Conversely, when the baseline NHHR exceeded the inflection points, a positive correlation was observed between NHHR and both all-cause mortality (HR: 1.11, 95% CI: 1.06–1.16) and cardiovascular mortality (HR: 1.08, 95% CI: 1.00–1.16).ConclusionsAmong US adults with diabetes or prediabetes, a U-shaped association was observed between NHHR and all-cause mortality, whereas an L-shaped association was identified with cardiovascular mortality. The inflection points for all-cause and cardiovascular mortality were 2.72 and 2.83, respectively.

Cardiovascular Risk Factors Predicting Cardiovascular and Cancer Deaths in a Middle-Aged Population Followed-Up for 61 Years until Extinction.

To study the relationships of cardiovascular risk factors with cancer and cardiovascular mortality in a cohort of middle-aged men followed-up for 61 years. A rural cohort of 1611 cancer- and cardiovascular disease-free men aged 40-59 years was examined in 1960 within the Italian Section of the Seven Countries Study, and 28 risk factors measured at baseline were used to predict cancer (n = 459) and cardiovascular deaths (n = 678) that occurred during 61 years of follow-up until the extinction of the cohort with Cox proportional hazard models. A model with 28 risk factors and cancer deaths as the end-point produced eight statistically significant coefficients for age, smoking habits, mother early death, corneal arcus, xanthelasma and diabetes directly related to events, and arm circumference and healthy diet inversely related. In the corresponding models for major cardiovascular diseases and their subgroups, only the coefficients of age and smoking habits were significant among those found for cancer deaths, to which healthy diet can be added if considering coronary heart disease alone. Following a competing risks analysis by the Fine-Gray method, risk factors significantly common to both conditions were only age, smoking, and xanthelasma. A sizeable number of traditional cardiovascular risk factors were not predictors of cancer death in a middle-aged male cohort followed-up until extinction.

Racial and ethnic disparities in the natural history of alcohol-associated liver disease in the United States.

Outcomes in alcohol-associated liver disease (ALD) are influenced by several race and ethnic factors, yet its natural history across the continuum of patients in different stages of the disease is unknown. We conducted a retrospective cohort study of U.S. adults from 2011 to 2018, using three nationally representative databases to examine potential disparities in relevant outcomes among racial and ethnic groups. Our analysis included logistic and linear regressions, along with competing risk analysis. Black individuals had the highest daily alcohol consumption (12.6 g/day) while Hispanic participants had the largest prevalence of heavy episodic drinking (33.5%). In a multivariable-adjusted model, Hispanic and Asian participants were independently associated with a higher ALD prevalence compared to Non-Hispanic White interviewees (OR: 1.4, 95% CI: 1.1-1.8 and OR: 1.5 95% CI:1.1-2.0, respectively), while Blacks participants had a lower ALD prevalence (OR: .7 95% CI: .6-.9), and a lower risk of mortality during hospitalization due to ALD (OR: .83 95% CI: .73-.94). Finally, a multivariate competing-risk analysis showed that Hispanic ethnicity had a decreased probability of liver transplantation if waitlisted for ALD (SHR: .7, 95% CI: .6-.8) along with female Asian population (HR: .40, 95% CI: .26-.62). After accounting for key social and biological health determinants, the Hispanic population showed an increased risk of ALD prevalence, even with lower alcohol consumption. Additionally, Hispanic and Asian female patients had reduced access to liver transplantation compared to other enlisted patients.

Prognostication and Interventional Guidance Using Acceleration-Ejection Time Ratio in Undifferentiated Paradoxical Low-Flow Low-Gradient Aortic Stenosis

BackgroundStudies in paradoxical low-flow low-gradient aortic stenosis (PLFAS) have demonstrated conflicting outcomes with variable survival advantage from aortic valve replacement (AVR). PLFAS is a heterogeneous composition of patients with uncertainty regarding true stenosis severity that continues to confound decision-making for AVR. ObjectivesThe purpose of this study was to investigate the utility of the Doppler acceleration (AT) to ejection (ET) time ratio (AT:ET) for prediction of prognosis and benefit from AVR in undifferentiated PLFAS. MethodsPatients with echocardiographic findings of PLFAS (aortic valve area <1.0 cm2 or indexed aortic valve area <0.6 cm2/m2, mean gradient <40 mm Hg, indexed stroke volume <35 mL/m2, and left ventricular ejection fraction ≥50%) were identified and grouped according to an AT:ET cutoff of 0.35. The primary outcome was a 5-year composite of cardiac mortality or AVR. Secondary outcomes included the individual components of the primary endpoint and all-cause mortality at 5 years. Effect of AVR was analyzed in the AT:ET <0.35 and ≥0.35 groups. ResultsA total of 171 PLFAS patients (median age 77.0 years, 57% women) were followed for a median of 8.9 years. AT:ET ≥0.35 was an independent predictor of the primary outcome (HR: 4.77 [95% CI: 2.94-7.75]; P < 0.001) with incremental value over standard indices of stenosis severity (net reclassification improvement: 0.57 [95% CI: 0.14-0.84]). AT:ET ≥0.35 also remained predictive of increased cardiac death (HR: 2.91 [95% CI: 1.47-5.76]; P = 0.002) and AVR (HR: 8.45 [95% CI: 4.16-17.1]; P < 0.001), respectively, following competing risk analysis. No difference in all-cause mortality was observed. AVR in the AT:ET ≥0.35 group was associated with significant reductions in 5-year cardiac (HR: 0.09 [95% CI: 0.02-0.36]; P < 0.001) and all-cause mortality (HR: 0.16 [95% CI: 0.07-0.38]; P < 0.001). No improvement in survival from AVR was demonstrated in AT:ET <0.35 patients. ConclusionsAT:ET ≥0.35 in PLFAS predicts poorer outcomes and/or need for AVR. In undifferentiated PLFAS patients, AT:ET may have a potential role in improving patient selection for prognostic AVR.