Competing Risks Framework Research Articles

Long-Term Ozone Exposure, COPD, and Asthma Mortality: A Retrospective Cohort Study in the Republic of Korea

Ozone concentrations have increased in recent decades, and several studies have reported that long-term exposure to ozone increases the mortality risk induced by respiratory conditions. However, research on cause-specific mortality related to ozone exposure and respiratory diseases remains scarce. We constructed a retrospective cohort of 5,360,032 adults aged ≥ 65 years from the National Health Insurance Service of Republic of Korea, and death certificates were obtained from Statistics Republic of Korea to determine the cause of death between 2010 and 2019. The daily maximum 8 h average levels of ozone during the warm season annually (May–September) and other air pollutants were determined for the residential district. We analyzed the data using a time-varying Cox proportional hazards model with individual- and district-level covariates, incorporating a competing risk framework to address deaths from causes other than chronic obstructive pulmonary disease (COPD) and asthma. In our single-pollutant model with a 3-year moving average, a 1 ppb increase in ozone exposure was associated with a hazard ratio (HR) of 1.011 (95% confidence interval [CI]: 1.008–1.013) for COPD mortality and an HR of 1.016 (95% CI: 1.011–1.022) for asthma mortality. In our model adjusted for the presence of underlying diseases and district-level variables, the HRs were 1.009 (95% CI: 1.008–1.014) for COPD and 1.017 (95% CI: 1.011–1.023) for asthma, respectively. These associations remained robust in our two-pollutant model, except for NO2 and COPD. A linear concentration–response relationship was identified between ozone concentration, COPD, and asthma mortality. In this large nationwide cohort study, long-term exposure to ozone was associated with an increased risk of death from COPD and asthma in older Korean adults.

Development and validation of a risk predictive nomogram for colon cancer-specific mortality: a competing risk model based on the SEER database

BackgroundUtilizing the SEER database, we developed a competing risk model along with a nomogram designed for the early identification of colon cancer-specific mortality (CSM) risk.MethodsClinical and pathological information, along with other significant data, were obtained from the SEER database. Patients were randomly divided into a training set and a validation set. We investigated the independent factors affecting CSM among colon cancer patients using univariate and multivariate analyses within a competing risk framework, ultimately developing a predictive tool for CSM in colon cancer.ResultsInvolving 40,261 individuals diagnosed with colon cancer, our study included 10,397 deaths directly due to the disease and an additional 5,828 from other causes. We used a competing risk model to predict cancer-specific mortality (CSM) in these patients. For the training dataset, the model’s area under the curve (AUC) for predicting 1-, 3-, and 5-year cancer-specific survival (CSS) was 0.835 (95% confidence interval [CI] 0.826 to 0.844), 0.849 (95% CI 0.843 to 0.855), and 0.843 (95% CI 0.836 to 0.850), respectively. In the validation group, the AUC values for the same time periods were 0.846 (95% CI 0.833 to 0.860), 0.853 (95% CI 0.843 to 0.862), and 0.846 (95% CI 0.835 to 0.856), respectively. In comparison, traditional survival analysis yielded higher cumulative CSM rates over time than those provided by our competing risk approach.ConclusionWe created a competitive risk assessment model along with a predictive tool designed to estimate CSM in patients with colon cancer. This nomogram demonstrates high accuracy and reliability, aiding medical professionals in making clinical decisions and developing patient follow-up plans.

Safety of hepatitis E vaccine in pregnancy: an emulated target trial following a mass reactive vaccination campaign in Bentiu internally displaced persons camp, South Sudan

Epidemic forms of hepatitis E cause high mortality among pregnant people, with case fatality risks over 30% and adverse fetal outcomes. In 2022, the first mass reactive vaccination campaign against hepatitis E was conducted in South Sudan with the HEV239 vaccine. We aimed to assess whether vaccination against hepatitis E in pregnancy increases the risk of fetal loss in a cohort of vaccinated and unvaccinated pregnant people. In this emulated target trial, an exhaustive pregnancy census was conducted in Bentiu internally displaced persons camp after the second of three vaccination rounds. Women and girls aged 14-45 years with no current jaundice or acute illness were eligible for participation. Individuals who consented were revisited 28 days after their delivery date to document the pregnancy outcome. We used an emulated target trial framework to address biases inherent in observational studies. We matched vaccinated to unvaccinated participants on age, gestational age, and vaccination propensity score and estimated cumulative incidence functions for fetal loss in vaccinated compared to unvaccinated women in a competing risks framework using the Aalen-Johansen estimator. Between May 16 and June 30, 2022, 3421 participants were enrolled and followed up for inclusion in analysis. Among 2741 women who had a pregnancy outcome after the start of the vaccination campaign, 67 (2·4%) were vaccinated before conception, 2036 (74·3%) were vaccinated during pregnancy, and 638 (23·2%) were not vaccinated. Among the 2407 women retained in the matched analyses, the cumulative risk of fetal loss among individuals vaccinated during pregnancy was 7·2% (95% CI 5·6-8·7) compared with 6·1% (3·7-9·2) among unvaccinated individuals, implying a risk ratio of 1·2 (95% CI 0·7-1·9). No evidence of increased risk of fetal loss was found among individuals vaccinated during pregnancy. Médecins Sans Frontières.

Extracorporeal Membrane Oxygenation for COVID-19 During the Delta and Omicron Waves in North America.

Clinical outcomes for patients with severe acute respiratory failure caused by different variants of the coronavirus disease 2019 (COVID-19) supported with extracorporeal membrane oxygenation (ECMO) are incompletely understood. Clinical characteristics, pre-ECMO management, and hospital mortality at 90 days for adults with COVID-19 who received venovenous ECMO (VV-ECMO) at North American centers during waves predominated by Delta (August 16 to December 12, 2021) and Omicron (January 31 to May 31, 2022) severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants were compared in a competing risks framework. One thousand seven hundred and sixty-six patients (1,580 Delta, 186 Omicron) received VV-ECMO for COVID-19 during the Delta- and Omicron-predominant waves in North American centers. In the unadjusted competing risks model, no significant difference was observed in risk of hospital mortality at 90 days between patients during the Delta- versus Omicron-predominant wave (subhazard ratio [sHR], 0.94; 95% confidence interval [CI], 0.74-1.19), but patients supported with VV-ECMO during the Omicron-predominant wave had a significantly lower adjusted risk of hospital mortality at 90 days (subhazard ratio, 0.71; 95% CI, 0.51-0.99). Patients receiving VV-ECMO during the Omicron-predominant wave had a similar unadjusted risk of hospital mortality at 90 days, but a significantly lower adjusted risk of hospital mortality at 90 days than those receiving VV-ECMO during the Delta-predominant wave.

Sudden cardiac death after myocardial infarction: individual participant data from pooled cohorts.

Risk stratification of sudden cardiac death after myocardial infarction and prevention by defibrillator rely on left ventricular ejection fraction (LVEF). Improved risk stratification across the whole LVEF range is required for decision-making on defibrillator implantation. The analysis pooled 20 data sets with 140 204 post-myocardial infarction patients containing information on demographics, medical history, clinical characteristics, biomarkers, electrocardiography, echocardiography, and cardiac magnetic resonance imaging. Separate analyses were performed in patients (i) carrying a primary prevention cardioverter-defibrillator with LVEF ≤ 35% [implantable cardioverter-defibrillator (ICD) patients], (ii) without cardioverter-defibrillator with LVEF ≤ 35% (non-ICD patients ≤ 35%), and (iii) without cardioverter-defibrillator with LVEF > 35% (non-ICD patients >35%). Primary outcome was sudden cardiac death or, in defibrillator carriers, appropriate defibrillator therapy. Using a competing risk framework and systematic internal-external cross-validation, a model using LVEF only, a multivariable flexible parametric survival model, and a multivariable random forest survival model were developed and externally validated. Predictive performance was assessed by random effect meta-analysis. There were 1326 primary outcomes in 7543 ICD patients, 1193 in 25 058 non-ICD patients ≤35%, and 1567 in 107 603 non-ICD patients >35% during mean follow-up of 30.0, 46.5, and 57.6 months, respectively. In these three subgroups, LVEF poorly predicted sudden cardiac death (c-statistics between 0.50 and 0.56). Considering additional parameters did not improve calibration and discrimination, and model generalizability was poor. More accurate risk stratification for sudden cardiac death and identification of low-risk individuals with severely reduced LVEF or of high-risk individuals with preserved LVEF was not feasible, neither using LVEF nor using other predictors.

Impact of radiotherapy on second primary lung cancer incidence and survival in esophageal cancer survivors

Esophageal cancer, ranked as the seventh most common cancer globally, encompasses squamous cell carcinoma and adenocarcinoma. Despite advancements in treatment modalities like surgery, chemotherapy, radiotherapy, and immunotherapy, radiotherapy, while crucial for enhancing local control and survival, poses risks for long-term side effects and the development of second primary malignancies (SPM), notably Second primary lung cancer (SPLC). This study aims to analyze the incidence of second primary lung cancer (SPLC) among esophageal cancer survivors, with a focus on the influence of radiotherapy, analyze variations across different demographic and clinical subgroups, and assess patient survival outcomes. Using data from the Surveillance, epidemiology, and end results (SEER) program on 56,493 esophageal cancer patients (2000–2020), we compared SPLC incidence in those with and without prior radiotherapy. We applied a competing risks framework, propensity score matching (PSM), and survival analyses to assess SPLC risk and radiotherapy’s impact. The study showed that patients treated with radiotherapy have a significantly higher long-term risk of SPLC compared to those without it. Radiotherapy significantly raised SPLC risk (HR 1.41, 95% CI 1.06–1.88), with higher SIRs particularly in younger patients and females. Post-PSM, there were significant differences in cancer-specific survival between esophageal cancer survivors with post-radiotherapy SPLC and those with only primary lung cancer. This cohort study shows that radiotherapy in esophageal cancer survivors increases SPLC risk but does not worsen survival compared to those with OPLC, highlighting the need for long-term monitoring and management.

Frailty model for multiple repairable systems hierarchically represented subject to competing risks

In this paper, we propose a statistical model to describe the behaviour of failure times associated with groups of repairable systems hierarchically represented, under a competing risks framework, considering the existence of unobserved heterogeneity that acts individually on systems of each group, as well as the possibility of imperfect repairs whose initial failure rate is in the form of the power law. In this context for the unobserved heterogeneity in the groups, we consider the multiplicative frailty. To illustrate the use of the proposed model, we consider a database with the failures of 38 agricultural machines categorized into five different groups. We understand that the tractor fleet corresponds to the farm's agricultural system, therefore the need for intervention in this system occurs with the failure of any unit, individually, in a serial structure, of competing risks.e On the other hand, the understanding of the time in which all the machinery that makes up the fleet will have required some intervention is obtained by analysing the results under a parallel structure.

Time-varying associations of patient and tumor characteristics with cancer survival: an analysis of SEER data across 14 cancer sites, 2004-2017.

Surveillance, Epidemiology, and End Results (SEER) cancer registries provides information about survival duration and cause of death for cancer patients. Baseline demographic and tumor characteristics such as age, sex, race, year of diagnosis, and tumor stage can inform the expected survival time of patients, but their associations with survival may not be constant over the post-diagnosis period. Using SEER data, we examined if there were time-varying associations of patient and tumor characteristics on survival, and we assessed how these relationships differed across 14 cancer sites. Standard Cox proportional hazards models were extended to allow for time-varying associations and incorporated into a competing-risks framework, separately modeling cancer-specific and other-cause deaths. For each cancer site and for each of the five factors, we estimated the relative hazard ratio and absolute hazard over time in the presence of competing risks. Our comprehensive consideration of patient and tumor characteristics when estimating time-varying hazards showed that the associations of age, tumor stage at diagnosis, and race/ethnicity with risk of death (cancer-specific and other-cause) change over time for many cancers; characteristics of sex and year of diagnosis exhibit some time-varying patterns as well. Stage at diagnosis had the largest associations with survival. These findings suggest that proportional hazards assumptions are often violated when examining patient characteristics on cancer survival post-diagnosis. We discuss several interesting results where the relative hazards are time-varying and suggest possible interpretations. Based on the time-varying associations of several important covariates on survival after cancer diagnosis using a pan-cancer approach, the likelihood of the proportional hazards assumption being met or corresponding interpretation should be considered in survival analyses, as flawed inference may have implications for cancer care and policy.

Recurrence and tumor-related death after resection of hepatocellular carcinoma in patients with metabolic syndrome

Metabolic syndrome (MS) is a growing epidemic and a risk factor for the development of hepatocellular carcinoma (HCC). This study investigated the long-term outcomes of liver resection (LR) for HCC in patients with MS. Rates, timing, patterns, and treatment of recurrences were investigated, and cancer-specific survivals were assessed. Between 2001 and 2021, data from 24 clinical centers were collected. Overall survival (OS), recurrence-free survival (RFS), and cancer-specific survival were analyzed as well as recurrence patterns and treatment. The analysis was conducted using a competing-risk framework. The trajectory of the risk of recurrence over time was applied to a competing risk analysis. For post-recurrence survival, death resulting from tumor progression was the primary endpoint, whereas deaths with recurrence relating to other causes were considered as competing events. In total, 813 patients were included in the study. Median OS was 81.4 months (range 28.1-157.0 months), and recurrence occurred in 48.3% of patients, with a median RFS of 39.8 months (range 15.7-174.7 months). Cause-specific hazard of recurrence showed a first peak 6 months (0.027), and a second peak 24 months (0.021) after surgery. The later the recurrence, the higher the chance of receiving curative intent approaches (p= 0.001). Size >5cm, multiple tumors, microvascular invasion, and cirrhosis were independent predictors of recurrence showing a cause-specific hazard over time. RFS was associated with death for recurrence (hazard ratio: 0.985, 95% CI: 0.977-0.995; p= 0.002). Patients with MS undergoing LR for HCC have good long-term survival. Recurrence occurs in 48% of patients with a double-peak incidence and time-specific hazards depending on tumor-related factors and underlying disease. The timing of recurrence significantly impacts survival. Surveillance after resection should be adjusted over time depending on risk factors. Metabolic syndrome (MS) is a growing epidemic and a significant risk factor for the development of hepatocellular carcinoma (HCC). The present study demonstrated that patients who undergo surgical resection for HCC on MS have a good long-term survival and that recurrence occurs in almost half of the cases with a double peak incidence and time-specific hazards depending on tumor-related factors and underlying liver disease. Also, the timing of recurrence significantly impacts survival. Clinicians should therefore adjust follow-up after surgery accordingly, considering timing of recurrence and specific risk factors. Also, the results of the present study might help design future trials on the use of adjuvant therapy following resection.

Incidence and outcomes of hospital-associated respiratory virus infections by viral species.

Although the incidence of hospital-associated respiratory virus infection (HARVI) is well recognized, the risk factors for infection and impact on patient outcomes are not well characterized. We identified a cohort of all inpatient admissions ≥24 hours duration at a single academic medical center from 2017 to 2020. HARVI were defined as respiratory virus detected in a test ordered after the 95th percentile of the virus-specific incubation period. Risk factors for HARVI were assessed using Cox proportional hazards models of the competing outcomes of HARVI and discharge. The associations between time-varying HARVI status and the rates of ICU admission, discharge, and in-hospital death were estimated using Cox-proportional hazards models in a competing risk framework. HARVI incidences were 8.8 and 3.0 per 10,000 admission days for pediatric and adult patients, respectively. For adults, congestive heart failure, renal disease, and cancer increased HARVI risk independent of their associations with length of stay. HARVI risk was also elevated for patients admitted in September-June relative to July admissions. For pediatric patients, cardiovascular and respiratory conditions, cancer, medical device dependence, and admission in December increased HARVI risk. Lengths of stay were longer for adults with HARVI compared to those without, and hospital-associated influenza A was associated with increased risk of death. Rates of ICU admission were increased in the 5 days after HARVI identification for adult and pediatric patients. HARVI was not associated with length of stay or death among pediatric patients. HARVI is associated chronic health conditions and increases morbidity and mortality.

Bleeding and Thrombosis in Patients with Cancer and Acute Venous Thromboembolism Requiring Urgent Procedures

BACKGROUND There are limited data of outcomes in patients who require anticoagulation interruption for a surgical procedure shortly after an acute VTE, especially in patients with cancer who are at higher risk for both hemorrhage and recurrent thrombosis. Our goal was to assess the incidence of recurrent thrombosis or major hemorrhage at 60-days following an urgent surgical procedure in patients with acute VTE (within one month prior to surgery). METHODS We performed a retrospective cohort study of patients with cancer at Memorial Sloan Kettering Cancer Center (from January 1 st 2021 to December 31 st 2022). Patients were eligible for inclusion if they were diagnosed with a new acute deep vein thrombosis or pulmonary embolism and underwent surgical procedure within 30-days following the acute VTE diagnosis. Recurrent VTE was defined as symptomatic new deep-vein thrombosis or pulmonary embolism, incidental new deep-vein thrombosis or pulmonary embolism involving segmental or more proximal pulmonary arteries, or fatal pulmonary embolism or unexplained death for which pulmonary embolism could not be ruled out as the cause. Major hemorrhage was characterized according to ISTH definition. Competing risk framework was used to estimate cumulative incidences of major hemorrhage, VTE and death at 30 and 60-days. RESULTS A total of 90 patients were included in this analysis. The median age was 73 years and 62% were female (Table 1). Surgical procedures were classified by their risk of bleeding with 64 patients undergoing lower bleeding risk procedures and 26 high-risk procedures (Table 1). There were 10 recurrent or new VTE within 60-days of surgery (60-day cumulative incidence of 8.9%, 95% CI 4.1-16%). The recurrent sites were deep venous (N=7) and new PE (N=3). There were 12 major hemorrhagic events within 60 days (cumulative incidence of 12%, 95% CI 6.5-20%). The most common sites of hemorrhage were the lower gastrointestinal tract and genitourinary system. The competing risk framework is shown graphically in Figure 1. Among patients who received IVC filters the incidence of recurrent VTE was 1.1% and major hemorrhage was 2.2%. The 60-day cumulative incidence of death following surgical procedure was 19% (95% 12-28%). There were no fatal VTE and 3 fatal hemorrhagic events. CONCLUSION Among patients with cancer undergoing surgical procedures within 30-days of an acute VTE, the rates of recurrent VTE and major hemorrhage are substantively higher than reported in non-surgical acute VTE cohorts. Placement of temporary IVC filters may improve short-term bleeding and thrombotic outcomes.

Introducing the role of the municipality of residence in studying the secondary migration of international migrants. Evidence from Lombardy (Italy)

AbstractSecondary internal and international movements of migrants are receiving increasing attention in Europe while research has so far focused on the characteristics of individuals who remigrate or plan to re‐emigrate, the attributes of the place that secondary migrants aim to leave have been less studied compared to other personal characteristics. This knowledge gap is primarily due to the fact that detailed information on the municipality of residence is largely unavailable in nationwide sample surveys. To fill this gap, after considering the time since migrants' arrival in Italy and previous internal mobility, we analyse the relationship between the characteristics of the municipality where migrants live and short‐term migration intentions of return, onward and internal migration in a competing risk framework. We focus on ethnic concentration (community hotspots and coldspots) and classification into central and marginal areas as critical characteristics of municipalities. We used a unique pooled data set that includes seven cross‐sectional surveys conducted between 2010 and 2016 by the Regional Observatory for Integration and Multiethnicity in the Northern Italian region of Lombardy. Municipal characteristics are strongly related to migrants' intentions: migrants who intend to move internally or to a third country are more likely live in urban, suburban, intermediate and peripheral areas and in the mountains. In contrast, the intention to return is not correlated with the characteristics of the municipality. The concentration of co‐nationals is also uncorrelated with short‐term migration intentions. We discuss the limitations of using a concentration indicator to study the relationship with secondary mobility.

Abstract 16393: Incident Cardiometabolic Risk Factors in Breast Cancer Patients Stratified by Race and Ethnicity

Background: The development of incident cardiometabolic risk factors in racial and ethnic minority groups of women with breast cancer (BC) has not been well-characterized. Hypothesis: We expect a higher risk of incident cardiometabolic risk factors [hypertension (HTN), diabetes (DM), dyslipidemia] in racial and ethnic minority women with BC without a history of these conditions compared with non-Hispanic White (NHW) women with BC. Methods: The Pathways Heart Study is a prospective cohort study of women with invasive BC diagnosed from 2005 to 2013 at Kaiser Permanente Northern California. Cumulative incidence rates of incident HTN, DM, and dyslipidemia determined from the electronic health record (using two separate ICD 9/10 codes in the 2 years prior to BC diagnosis, lab values, and medication dispensings) were calculated using a competing risk framework for overall death. Sub-distribution hazard ratios for incident HTN, DM, and dyslipidemia were estimated using Fine and Gray proportional hazards regression, adjusted for a priori identified covariables, and stratified by race and ethnicity. Results: A total of 14,942 women with BC had mean age 61.2 years and were 65% NHW, 7.5% Black, 14.4% Asian, 11.9% Hispanic, 0.4% Pacific Islander, and 0.8% American Indian/Alaska Native. Compared to NHW women, Black, Hispanic, Asian, and Pacific Islander women had higher risk of incident DM (Table 1). Black and Asian women had higher risk of incident HTN compared with NHW women. Asian women had higher risk of incident dyslipidemia compared with NHW women. Conclusions: Racially and/or ethnically diverse women with BC experienced higher risk of incident DM, HTN, and dyslipidemia compared with NHW women with BC. Asian women consistently had a higher risk of each cardiometabolic risk factor. It is critical to better characterize health disparities in the field of cardio-oncology to inform future cardiovascular disease prevention and treatment strategies.

Trajectories of patients relisted for liver transplantation

Introduction and ObjectivesRecurrent cirrhosis complicates 10-30% of Liver transplants (LT) and can lead to consideration for re-transplantation. We evaluated the trajectories of relisted versus primary listed patients on the waitlist using a competing risk framework. Materials and MethodsWe retrospectively examined 1,912 patients listed for LT at our centre between from 2012 to 2020. Cox proportional hazard models were used to assess overall survival (OS) by listing type and competing risk analysis Fine-Gray models were used to assess cumulative incidence of transplant by listing type. Results1,731 patients were included (104 relisted). 44.2% of relisted patients received exception points vs. 19.8% of primary listed patients (p<0.001). Patients relisted without exceptions, representing those with graft cirrhosis, had the worst OS (HR: 4.17, 95%CI 2.63 – 6.67, p=<0.0001) and lowest instantaneous rate of transplant (HR: 0.56, 95%CI 0.38 – 0.83, p=0.006) than primary listed with exception points. On multivariate analysis listing type, height, bilirubin and INR were associated with cumulative incidence of transplant, while listing type, bilirubin, INR, sodium, creatinine were associated with OS. Within relisted patients, there was a trend towards higher mortality (HR: 1.79, 95%CI 0.91 – 3.52, p=0.08) and low transplant incidence (HR: 0.51, 95%CI 0.22 – 1.15, p=0.07) for graft cirrhosis vs other relisting indications. ConclusionsPatients relisted for LT are carefully curated and comprise a minority of the waitlist population. Despite their younger age, they have worse liver/kidney function, poor waitlist survival, and decreased transplant incidence suggesting the need for early relisting, while considering standardized exception points.

Transplant Candidate Outcomes After Declining a DCD Liver in the United States.

In the context of the organ shortage, donation after circulatory death (DCD) provides an opportunity to expand the donor pool. Although deceased-donor liver transplantation from DCD donors has expanded, DCD livers continue to be discarded at elevated rates; the use of DCD livers from older donors, or donors with comorbidities, is controversial. Using US registry data from 2009 to 2020, we identified 1564 candidates on whose behalf a DCD liver offer was accepted ("acceptors") and 16 981 candidates on whose behalf the same DCD offers were declined ("decliners"). We characterized outcomes of decliners using a competing risk framework and estimated the survival benefit (adjusted hazard ratio [95% confidence interval]) of accepting DCD livers using Cox regression. Within 10 y of DCD offer decline, 50.9% of candidates died or were removed from the waitlist before transplantation with any type of allograft. DCD acceptors had lower mortality compared with decliners at 10 y postoffer (35.4% versus 48.9%, P < 0.001). After adjustment for candidate covariates, DCD offer acceptance was associated with a 46% reduction in mortality (0.54 [0.49-0.61]). Acceptors of older (age ≥50), obese (body mass index ≥30), hypertensive, nonlocal, diabetic, and increased risk DCD livers had 44% (0.56 [0.42-0.73]), 40% (0.60 [0.49-0.74]), 48% (0.52 [0.41-0.66]), 46% (0.54 [0.45-0.65]), 32% (0.68 [0.43-1.05]), and 45% (0.55 [0.42-0.72]) lower mortality risk compared with DCD decliners, respectively. DCD offer acceptance is associated with considerable long-term survival benefits for liver transplant candidates, even with older DCD donors or donors with comorbidities. Increased recovery and utilization of DCD livers should be encouraged.

Stereotactic body radiation therapy for sarcoma pulmonary metastases

Background/PurposeStereotactic body radiation therapy (SBRT) is standard for patients with inoperable early-stage NSCLC. We hypothesized that SBRT for sarcoma pulmonary metastases would achieve high rates of local control with acceptable toxicity and that patients with oligometastatic disease may achieve prolonged survival following SBRT. Materials/MethodsThis retrospective review included consecutive patients at our institution treated with SBRT for sarcoma pulmonary metastases. Cumulative incidence of local failure (LF) was estimated using a competing risks framework. ResultsWe identified 66 patients treated to 95 pulmonary metastases with SBRT. The median follow-up from the time of SBRT was 36 months (95% CI 34 – 53 months). The cumulative incidence of LF at 12 and 24 months was 3.1% (95% CI 0.9 – 10.6%) and 7.4% (95% CI 4.0% - 13.9%), respectively. The 12- and 24-month overall survival was 74% (95% CI 64 – 86%) and 49% (38 – 63%), respectively. Oligometastatic disease, intrathoracic only disease, and performance status were associated with improved survival on univariable analysis. Three patients had grade 2 pneumonitis, and one patient had grade 2 esophagitis. No patients had ≥ grade 3+ toxicities. ConclusionTo the best of our knowledge, this is the largest series of patients treated with SBRT for pulmonary sarcoma metastases. We observed that SBRT offers an effective alternative to surgical resection with excellent local control and low proportions of toxicity.

Effect of proprotein convertase subtilisin/kexin type 9 inhibition on cancer events: A pooled, post hoc, competing risk analysis of alirocumab clinical trials.

Assess the risk of new and worsening cancer events among participants who received the lipid-lowering therapy alirocumab, a proprotein convertase subtilisin/kexin type 9 inhibitor. Pooled post hoc analysis. Six phase 3 or phase 4 placebo-controlled randomised trials with alirocumab. A total of 24,070 patients from the safety population with complete dosing data (alirocumab, n = 12,533; placebo, n = 11,537). Alirocumab 75 mg, alirocumab 150 mg, alirocumab 75 mg increasing to 150 mg if low-density lipoprotein cholesterol <50 mg/dL not achieved, or placebo, all every 2 weeks. All participants received background high-intensity or maximum-tolerated statin therapy. The first new or worsening incident cancer events were assessed during the treatment-emergent adverse event period. Four outcomes were evaluated: any-neoplasm, malignant neoplasms, broad definition of hormone-sensitive cancers, and stricter definition of hormone-sensitive cancers. Sub-distribution hazard ratios and 95% confidence intervals (CIs) were estimated using a competing risk framework, with death as a competing risk. Considering both treatment arms in aggregate, 969 (4.03%), 779 (3.24%), 178 (0.74%) and 167 (0.69%) patients developed any neoplasm, malignant neoplasms, broad definition of hormone-sensitive cancer and strict definition of hormone-sensitive cancer events, respectively. There was no significant difference in the risk of having any neoplasm in the alirocumab versus the placebo group (sub-distribution hazards ratio [95% CI], 0.93 [0.82-1.1]; p = 0.28). A nominally lower risk of having any neoplasms with alirocumab was observed among subjects aged ≥64 years (sub-distribution hazards ratio 0.83; 95% CI, 0.70-0.99). Intensive low-density lipoprotein cholesterol lowering with a proprotein convertase subtilisin/kexin type 9 inhibitor combined with statin does not appear to increase the risk of new or worsening cancer events.

Pathological and radiological response following neoadjuvant treatments in primary localized resectable myxofibrosarcoma and undifferentiated pleomorphic sarcoma of the extremities and trunk wall.

To explore the correlation between pathological and radiological response to preoperative treatments and outcome in surgically treated patients with myxofibrosarcoma (MFS) and undifferentiated pleomorphic sarcoma (UPS). All consecutive patients with primary localized MFS and UPS of the extremities and trunk wall surgically treated with curative intent at our center (2005-2021) were included. Clinical data including residual visible tumor (VT%) on surgical specimen and Response Evaluation Criteria in Solid Tumor (RECIST) were retrieved. Kaplan-Meier curves for overall survival and disease-free survival, and cumulative incidence of local relapse and distant metastasis were estimated in a competing risk framework according to RECIST and VT%, overall and by treatment group. Cox and Fine and Gray multivariable models were performed. Of 693 patients affected by primary MFS and UPS, 233 (66 MFS and 167 UPS) were treated by neoadjuvant chemotherapy (naChT), radiotherapy (naRT), or both (naChT-RT). VT% was ≤5% in 13/46 (28.2%), 24/99 (24.2%), and 40/88 (45.4%) patients, respectively. There were 11/46 (29.7%), 22/99 (22.7%), and 23/88 (26.1%) RECIST partial responses and 18/46 (48.6%), 59/99 (60.8%), and 60/88 (68.2%) RECIST stable disease, respectively. In naChT, a trend for a better survival was observed when VT% ≤5% (p=.09), whereas RECIST partial responses and stable disease had the same outcome. VT% was not associated with outcome in naRT or naChT-RT, whereas RECIST response was. In primary localized MFS and UPS treated with neoadjuvant therapies, VT% seems more relevant than size reduction after naChT, whereas the opposite is true when naRT is administered alone or concurrent to ChT.

Derivation and validation of predictive indices for cardiac readmission after coronary and valvular surgery – A multicenter study

ObjectiveTo derive and validate models to predict the risk of a cardiac readmission within one year after specific cardiac surgeries using information that is commonly available from hospital electronic medical records. MethodsIn this retrospective cohort study, we derived and externally validated clinical models to predict the likelihood of cardiac readmissions within one-year of isolated CABG, AVR, and combined CABG+AVR in Ontario, Canada, using multiple clinical registries and routinely collected administrative databases. For all adult patients who underwent these procedures, multiple Fine and Gray subdistribution hazard models were derived within a competing-risk framework using the cohort from April 2015 to March 2018 and validated in an independent cohort (April 2018 to March 2020). ResultsFor the model that predicted post-CABG cardiac readmission, the c-statistic was 0.73 in the derivation cohort and 0.70 in the validation cohort at one-year. For the model that predicted post-AVR cardiac readmission, the c-statistic was 0.74 in the derivation and 0.73 in the validation cohort at one-year. For the model that predicted cardiac readmission following CABG+AVR, the c-statistic was 0.70 in the derivation and 0.66 in the validation cohort at one-year. ConclusionsPrediction of one-year cardiac readmission for isolated CABG, AVR, and combined CABG+AVR can be achieved parsimoniously using multidimensional data sources. Model discrimination was better than existing models derived from single and multicenter registries.

Educational Gradient in Unintended First Births in Korea

A number of studies have used samples from Western societies to assess educational differences in the likelihood of unintended pregnancies and births, but the issue is vastly understudied in Korea. To fill the gap in the literature, this paper draws data from the two most recent rounds of the National Survey on Fertility, Family Health, and Welfare ( N = 20,669), and adopted a competing risks framework to estimate the hazards of an intended first birth and unintended first birth relative to no birth. Results from discrete-time event history analyses indicate that women’s educational attainment significantly reduces the odds of unintended first childbirth, even after accounting for various sociodemographic factors. Women with two- and four-year college degrees were 47.5% and 63.9% less likely to experience unintended childbearing compared with those without a high school degree. Women’s higher educational attainment is also negatively associated with the odds of intended childbearing relative to no birth. Hence, the present study suggests that there is a strong negative association between unintended childbearing and educational attainment among Korean women. These results are in accordance with Western patterns, and do not support an inverted correlation reported in Japan. Interaction between gender role ideology and educational attainment also indicated that women’s higher education tends to reduce the probability of experiencing unintended childbirth except when women have a very strong beliefs in gender equity. A better understanding on the determinants of unintended childbearing may be useful for identifying vulnerable segments of the population and preventing the intergenerational transmission of social disadvantages through fertility behaviors.