Fine-Gray Competing Risk Regression Research Articles

Development and validation of prediction model for prolonged mechanical ventilation after total thoracoscopic valve replacement: a retrospective cohort study

Total thoracoscopic valve replacement (TTVR) is a minimally invasive alternative to traditional open-heart surgery. However, some patients undergoing TTVR experience prolonged mechanical ventilation (PMV). Predicting PMV risk is crucial for optimizing perioperative management and improving outcomes. We conducted a retrospective cohort study of 2,319 adult patients who underwent TTVR at a tertiary care center between January 2017 and May 2024. PMV was defined as mechanical ventilation exceeding 72 h post-surgery. A Fine-Gray competing risks regression model was developed and validated to identify predictors of PMV. Significant predictors of PMV included cardiopulmonary bypass time, ejection fraction, New York Heart Association grading, serum albumin, atelectasis, pulmonary infection, pulmonary edema, age, need for postoperative dialysis, hemoglobin levels, and PaO2/FiO2. The model demonstrated good discriminative ability, with areas under the receiver operating characteristic curves of 0.747 in the training set and 0.833 in the validation set. Calibration curves showed strong agreement between predicted and observed PMV probabilities. Decision curve analysis indicated clinical utility across a range of threshold probabilities. Our predictive model for PMV following TTVR demonstrates strong performance and clinical utility. It helps identify high-risk patients and tailor perioperative management to reduce PMV risk and improve outcomes. Further validation in diverse settings is recommended.

Association between radiation therapy for primary endometrial cancer and risk of second primary malignancies: a retrospective cohort study

Our objective was to evaluate the association of adjuvant radiation therapy (RT) to subsequent second primary malignancies (SPMs) in endometrial cancer survivors. Patients with endometrial cancer as their first malignancy were identified from 8 registries of the Surveillance, Epidemiology, and End Results (SEER) database. SPMs were defined as any type of primary malignancy that occurred more than 12 months after the diagnosis of endometrial cancer. Fine-Gray competing risk regression and Poisson regression were used to evaluate the radiotherapy-associated risk (RR) for SPMs. The Kaplan-Meier method was applied to assess the survival outcomes of endometrial cancer patients. Of 62,108 endometrial cancer patients,16,846 patients (27.12%) were in the RT group, and 45,262 patients (72.88%) were in the no-RT group. During the 30-year follow-up period, the cumulative incidence of SPMs was 20.9% and 19.7% in each group, respectively. In both multivariable competing risk regression analysis and Poisson regression analysis, adjuvant RT was found to be associated with a higher risk of developing colon and rectum cancer (adjusted hazard ratio (HR), 1.29; 95% confidence interval (CI), 1.12–1.50; P < 0.001; adjusted RR, 1.29; 95% CI, 1.11–1.49; P < 0.001), lung and bronchus cancer (adjusted HR, 1.27; 95% CI, 1.08–1.50; P = 0.004; adjusted RR, 1.26; 95% CI, 1.07–1.49; P = 0.005), vulva cancer (adjusted HR, 1.72; 95% CI, 1.04–2.85; P = 0.036; adjusted RR, 1.74; 95% CI, 1.03–2.88; P = 0.035), urinary bladder cancer (adjusted HR, 1.86; 95% CI, 1.41–2.46; P < 0.001; adjusted RR, 1.85; 95% CI, 1.40–2.44; P < 0.001), and non-Hodgkin lymphoma (adjusted HR, 1.37; 95% CI, 1.06–1.77; P = 0.016; adjusted RR, 1.37; 95% CI, 1.05–1.76; P = 0.017). However, a slightly decreased risk of breast cancer was observed in patients who underwent adjuvant RT (adjusted HR, 0.89; 95% CI, 0.80–0.98; P = 0.021; adjusted RR, 0.88; 95% CI, 0.80–0.98; P = 0.020). The RR for colon and rectum cancer decreased with age and elevated with increasing latency since endometrial cancer diagnosis, and the RR for urinary bladder cancer showed a similar tendency with latency. SPMs can significantly impair the survival outcomes of primary endometrial cancer survivors. Our findings suggest that adjuvant RT for endometrial cancer patients increases the risk of non-Hodgkin lymphoma and several types of solid cancer. Long-term surveillance of these patients should be recommended for detecting SPMs.

Smoking and sudden cardiac death in patients with previous coronary artery disease.

Smoking is a known risk for sudden cardiac death (SCD) in the general population. However, its significance in patients with acute coronary syndrome (ACS), a condition that also elevates the risk of SCD, is disputable. A total of 9704 consecutive ACS patients with available smoking data were included in the analysis. Comprehensive patient data were obtained from the Mass Data in Detection and Prevention of Serious Adverse Events in Cardiovascular Disease research database. A composite endpoint of SCD, SCD aborted by successful resuscitation and accurate implantable cardioverter defibrillator therapy to otherwise potentially fatal ventricular fibrillation/ventricular tachycardia was used. Univariate, age- and sex-adjusted, and a multivariate fine-gray competing risk regression with adjustment to traditional risk factors was conducted. Median follow-up time was 6.8 years (IQR, 4.1-10.2), and 454 (4.7%) SCD cases were identified. At the baseline, 23.7% (N = 2444) were active smokers, and 20.8% (N = 2146) were ex-smokers. In the multivariate model, active smokers had an elevated risk of 1.79 (95% CI, 1.41-2.27; P < 0.001) for future SCD. Ex-smokers had no elevated risk for SCD in fine-gray subdistribution hazard. Also, active smokers were notably younger (mean age 58.7 years) than non- or ex-smokers (71.1 years and 68.9 years, respectively, P < 0.001 for both comparisons). Active smokers had a 79% higher risk of SCD when compared with nonsmokers. Smoking cessation should be heavily encouraged after ACS. Also, a person's smoking status should be considered in further studies developing SCD and implantable cardioverter defibrillator-benefit risk scores.

Initial Defibrillator Pad Position and Outcomes for Shockable Out-of-Hospital Cardiac Arrest

Ventricular fibrillation (VF) or pulseless ventricular tachycardia (pVT) are the most treatable causes of out-of-hospital cardiac arrest (OHCA). Yet, it remains unknown if defibrillator pad position, placement in the anterior-posterior (AP) or anterior-lateral (AL) locations, impacts patient outcomes in VF or pVT OHCA. To determine the association between initial defibrillator pad placement position and OHCA outcomes for patients presenting with VF or pVT. This prospective cohort study included patients with OHCA and VF or pVT treated by a single North American emergency medical services (EMS) agency from July 1, 2019, through June 30, 2023. The study included patients with OHCA treated by a large suburban fire-based EMS agency that covers a population of 550 000. Consecutive patients with an initial EMS-assessed rhythm of VF or pVT receiving EMS defibrillation were included. Pediatric patients (younger than 18 years), interfacility transfers, arrests of obvious traumatic etiology, and patients with preexisting do-not-resuscitate status were excluded. AP or AL pad placement. Return of spontaneous circulation (ROSC) at any time with secondary outcomes of pulses present at emergency department (ED) arrival, survival to hospital admission, survival to hospital discharge, and functional survival at hospital discharge (cerebral performance category score of 2 or less). Measures included adjusted odds ratios (aOR), multivariable logistic regressions, and Fine-Gray competing risks regression. A total of 255 patients with OHCA were included (median [IQR] age, 66 [55-74] years; 63 females [24.7%]), with initial pad positioning documented as either AP (158 patients [62.0%]; median [IQR] age, 65 [54-74] years; 37 females [23.4%]) or AL (97 patients [38.0%]; median [IQR] age, 66 [57-74] years; 26 females [26.8%]). Patients with AP placement had higher adjusted odds ratio (aOR) of ROSC at any time (aOR, 2.64 [95% CI, 1.50-4.65]), but not significantly different odds of pulses present at ED arrival (1.34 [95% CI, 0.78-2.30]), survival to hospital admission (1.41 [0.82-2.43]), survival to hospital discharge (1.55 [95% CI, 0.83-2.90]), or functional survival at hospital discharge (1.86 [95% CI, 0.98-3.51]). Competing risk analysis found significantly greater cumulative incidence of ROSC among those at risk with initial AP placement compared with AL (subdistribution hazard ratio, 1.81 [95% CI, 1.23-2.67]; P = .003). In this cohort study of patients with OHCA and VF or pVT, AP defibrillator pad placement was associated with higher ROSC compared with AL placement.

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.

Association between radiotherapy and the risk of second primary malignancies in breast cancer patients with different estrogen receptor statuses.

Breast cancer is the most common cancer among women. Second primary malignancies (SPMs) related to radiotherapy are significant complications. This study aims to investigate the correlation between radiotherapy and the occurrence of SPMs in breast cancer patients with different estrogen receptor statuses. We used data from the Surveillance, Epidemiology, and End Results (SEER) database, selecting estrogen receptor(+) and estrogen receptor(-) breast cancer patients from 1990 to 2015, with SPMs as the outcome measure. Fine-Gray competing risks regression and Poisson regression were employed to analyze the relationship between radiotherapy and the risk of SPMs in different estrogen receptor status groups. Radiotherapy was associated with an increased risk of lung cancer, melanoma, non-Hodgkin lymphoma, and leukemia in estrogen receptor(+) patients. In estrogen receptor(-) patients, radiotherapy was linked to an increased risk of brain cancer and leukemia. The cumulative incidence, standardized incidence ratio, and subgroup analyses showed consistent results. In the dynamic assessment of radiotherapy-related risks, estrogen receptor(+) patients aged 50-70 exhibited a higher risk of leukemia and melanoma. Lung cancer risk was highest during a latency period of 20-30 years, while melanoma, non-Hodgkin lymphoma, and leukemia risks peaked within the first 10 years. For estrogen receptor(-) patients, brain cancer risk was higher between ages 50 and 70, and leukemia risk was elevated between ages 20 and 50. Postoperative radiotherapy for breast cancer is associated with an increased risk of SPMs, with risks varying by estrogen receptor status and SPM type. Further research into the prevention of radiotherapy-related SPMs in different estrogen receptor status groups is crucial.

The Associations of Sensory Impairment With 10-Year Risk of Dementia and Alzheimer's Disease: The Health and Retirement Study, 2010-2020.

Studies have examined the association between dual sensory impairment and late-life cognitive outcomes in the U.S with inconsistent findings. To examine the associations between sensory impairment and 10-year risk of dementia or Alzheimer's disease among U.S. adults aged ≥ 50. A prospective cohort study based on the Health and Retirement Study from 2010 to 2020. Individuals aged ≥ 50 years without self-reported dementia and Alzheimer's disease in 2010 were included in the analysis. Self-reported visual and hearing impairments were measures in 2010. Main failure events included self-reported incident dementia and Alzheimer's disease over a 10-year follow-up period. Participants were categorized as having no visual or hearing impairment, visual impairment only, hearing impairment only, and dual sensory impairment. Fine-Gray competing risk regression model was applied to estimate the associations of sensory impairment with incident dementia and Alzheimer's disease, adjusted for demographic characteristics, health behaviors, and health conditions at baseline. Of 20,248 identified individuals, 14.6% had visual impairment only, 11.2% had hearing impairment only, and 9.1% had dual impairment at baseline. After adjusting for all covariates, dual sensory impairment was associated with higher risk of dementia (HR = 1.46, 95% CI: 1.23-1.73) and Alzheimer's disease (HR = 1.35, 95% CI: 1.03-1.76). Visual impairment only was also associated with incident dementia and Alzheimer's disease among individuals <65 years. Older adults in the U.S. with visual and hearing impairments simultaneously had a particularly greater risk of dementia and Alzheimer's disease, indicating the needs of targeted screening for timely treatment and further prevention of dementia and Alzheimer's disease.

Effect of Preoperative Mitral Regurgitation on LVAD Outcomes in Patients with Elevated Pulmonary Vascular Resistance.

In patients with end-stage heart failure who undergo left ventricular assist device (LVAD) implantation, higher pulmonary vascular resistance (PVR) is associated with higher right heart failure rates and ineligibility for heart transplant. Concomitant mitral regurgitation (MR) could potentially worsen pulmonary hemodynamics and lead to worse outcomes; however, its effects in this patient population have not been specifically examined. Using an institutional database spanning November 2003 to August 2017, we retrospectively identified patients with elevated PVR who underwent LVAD implantation. Patients were stratified by concurrent MR: moderate/severe (PVR + MR) vs. mild/none (PVR - MR). Cumulative incidence functions and Fine-Gray competing risk regression were performed to assess the effect of MR on heart transplant rates and overall survival during index LVAD support. Of 644 LVAD recipients, 232 (171 HeartMate II, 59 HeartWare, 2 HeartMate III) had baseline PVR > 3 Woods units; of these, 124 (53%) were INTERMACS 1-2, and 133 (57%) had moderate/severe MR (≥ 3 +). Patients with PVR + MR had larger a baseline left ventricular end-diastolic diameter than patients with PVR - MR (87.9 ± 38.2 mm vs. 75.9 ± 38.0 mm; P = 0.02). Median clinical follow-up was 18.8 months (interquartile range: 4.7-36.4 months). Moderate/severe MR was associated with lower mortality rates during index LVAD support (adjusted hazard ratio 0.64, 95% CI 0.41-0.98; P = 0.045) and higher heart transplant rates (adjusted odds ratio 2.86, 95% CI 1.31-6.25; P = 0.009). No differences in stroke, gastrointestinal bleeding, or right heart failure rates were observed. Among LVAD recipients with elevated preoperative PVR, those with moderate/severe MR had better overall survival and higher transplant rates than those with mild/no MR. These hypothesis-generating findings could be explained by incremental LVAD benefits resulting from reduction of MR and better LV unloading in a subset of patients with larger ventricles at baseline. In patients with preoperative elevated PVR, MR severity may be a prognostic sign that can inform patient selection for end-stage heart failure therapy.

Association of Definitive Radiotherapy for Esophageal Cancer and the Incidence of Secondary Head and Neck Cancers: A SEER Population-Based Study.

Impact of radiotherapy (RT) for esophageal cancer (EC) patients on the development of secondary head and neck cancer (SHNC) remains equivocal. The objective of this study was to investigate the link between definitive RT used for EC treatment and subsequent SHNC. This study was conducted using the Surveillance, Epidemiology, and End Results (SEER) database to collect the data of primary EC patients. Fine-Gray competing risk regression and standardized incidence ratio (SIR) and propensity score matching (PSM) method were used to match SHNC patients with only primary head and neck cancer (HNC) patients. Overall survival (OS) rates were applied by Kaplan-Meier analysis. In total, 14,158 EC patients from the SEER database were included, of which 9,239 patients (65.3%) received RT and 4,919 patients (34.7%) received no radiation therapy (NRT). After a 12-month latency period, 110 patients (1.2%) in the RT group and 36 patients (0.7%) in the NRT group experienced the development of SHNC. In individuals with primary EC, there was an increased incidence of SHNC compared to the general US population (SIR = 5.95, 95% confidence interval (CI): 5.15 - 6.84). Specifically, the SIR for SHNC was 8.04 (95% CI: 6.78 - 9.47) in the RT group and 3.51 (95% CI: 2.64 - 4.58) in the NRT group. Patients who developed SHNC after RT exhibited significantly lower OS compared to those after NRT. Following PSM, the OS of patients who developed SHNC after RT remained significantly lower than that of matched patients with only primary HNC. An association was discovered between RT for EC and increased long-term risk of SHNC. This work enables radiation oncologists to implement mitigation strategies to reduce the long-term risk of SHNC in patients who have received RT following primary EC.

Suicide among patients with oral cancer: A population-based study

BackgroundPatients with oral cancer usually experience disfigurement and dysfunction which are shared risk factors of suicide. The aim of the study was to comprehensively assess the characteristics of suicide and risk factors for suicide in patients with oral cancer. MethodsSurveillance, Epidemiology, and End Results database was used to acquire information of patients with common malignant tumors including oral cancer from 1975 to 2020. The aim was to explore the incidence of suicide, and timing of suicide among patients with oral cancer. A Fine-Gray competing risks regression model was employed to analyze risk factors associated with suicide among patients with various demographic and tumor characteristics. ResultsTotally, 7685 patients with different malignant tumors committed suicide. Among them, 203 patients with oral cancer died due to suicide, presenting a suicide rate of 54.5/100,000 person-years, which was almost 3.5 times that of the US general population and 1.5 times that of the overall US patients with cancer in our study. Approximately 18 %, 40 %, and 55 % of suicides occurred in first year, first 3 years, and first 5 years after diagnosis. Being male, White race, and having a single primary tumor might be regarded as the risk factors for suicide. ConclusionAs oral cavity is closely associated with appearance, pronunciation and ingestion, patients with oral cancer have a significant high risk of suicide. Tremendous attention needs to be paid to patients with oral cancer particularly those exhibiting characteristics associated with a high risk of suicide.

Favorable prostate-specific antigen levels correlate with a worse prognosis in high-grade prostate cancer: a population-based analysis.

To compare the association between prostate-specific antigen (PSA) levels and prostate cancer-specific mortality (PCSM), and the effectiveness of local treatment in patients with high-grade and low-grade prostate cancer (PCa). This retrospective cohort study enrolled patients diagnosed with clinically localized PCa (cT1-4N0M0) from January 2010 to December 2020 in the Surveillance, Epidemiology and End Results (SEER) database. Fine-Gray competing risk regression analysis was conducted to generate cumulative incidence plots and estimate the hazards ratio (HR) and 95% confidence interval (95% CI) of PCSM. Multivariable restricted cubic spline (RCS) analysis was used to examine the non-linear associations of continuous values of PSA levels with PCSM. Inverse probability of treatment weighting (IPTW) was employed to minimize imbalances in baseline characteristics between different local treatment cohorts. A total of 392083 eligible patients were included in the study, including 327659 low-grade (Gleason score [GS]≤7) PCa and 64424 high-grade (GS≥8) PCa. In multivariate Fine-Gray competing risk regression analysis, using PSA levels of 4.1-10.0ng/ml as the reference, the adjusted HR among high-grade patients with PSA levels ≤2.5ng/ml, 2.6-4.0ng/ml, 10.1-20.0ng/ml and >20.0ng/ml were 1.988 (95% CI=1.677-2.358), 1.411 (95% CI=1.194-1.668), 1.472 (95% CI=1.351-1.603) and 2.506 (95% CI=2.318-2.709), respectively. Among low-grade PCa, the adjusted HR were 0.985 (95% CI=0.800-1.213), 0.727 (95% CI=0.602-0.877), 1.844 (95% CI=1.679-2.026) and 3.574 (95% CI=3.220-3.966), respectively. Multivariable-adjusted RCS analysis showed a U/J-shaped distribution relationship between PSA levels and PCSM in high-grade PCa, while there was a positive association between PSA levels and PCSM in low-grade PCa. As for local treatment effectiveness, radiation therapy (RT) provided better control of PCSM compared to radical prostatectomy (RP) and RP+RT in high-grade PCa, while RP provided better control of PCSM compared to RT and RP+RT in low-grade PCa. Low PSA level (≤2.5ng/ml) is significantly associated with very high risk of PCSM in high-grade localized PCa but not in low-grade localized PCa. High-grade localized PCa patients benefit more from RT in terms of PCSM control, while low-grade localized PCa patients benefit more from RP. High-grade localized PCa with low PSA level may be a unique subgroup that could benefit from novel risk stratification strategies in PCa, which requires further studies to investigate the potential of developing novel therapeutic strategies, prognostic tools, and clinical management approaches.

Concomitant use of lansoprazole and ceftriaxone is associated with an increased risk of ventricular arrhythmias and cardiac arrest in a large Japanese hospital database

To determine whether concomitant use of ceftriaxone and oral or intravenous lansoprazole increases the risk of ventricular arrhythmia and cardiac arrest in the real-world setting in Japan. The data analyzed were obtained from the JMDC hospital-based administrative claims database for the period April 2014 to August 2022. Patients who received a proton pump inhibitor (PPI) while receiving ceftriaxone or sulbactam/ampicillin were identified. The frequency of ventricular arrhythmia and cardiac arrest was analyzed according to whether oral or intravenous PPI was concomitant with ceftriaxone or sulbactam/ampicillin. Estimates of the incidence of ventricular arrhythmia and cardiac arrest were then compared among the groups, using the Fine-Gray competing risk regression model. The results showed that the risk of ventricular arrhythmia and cardiac arrest was significantly higher with concomitant ceftriaxone and oral lansoprazole (hazard ratio 2.92, 95% confidence interval 1.99-4.29, P<0.01) or intravenous lansoprazole (hazard ratio 4.57, 95% confidence interval 1.24-16.80, P=0.02) than with concomitant sulbactam/ampicillin and oral or intravenous lansoprazole. Oral and intravenous lansoprazole may increase the risk of ventricular arrhythmia and cardiac arrest in patients who are receiving ceftriaxone.

Geriatric conditions and healthcare utilization among older adults living in subsidized housing.

Nearly 2.9 million older Americans with lower incomes live in subsidized housing. While regional and single-site studies show that this group has higher rates of healthcare utilization compared to older adults in the general community, little is known about healthcare utilization nationally nor associated risk factors. We conducted a retrospective cohort study of Medicare beneficiaries aged ≥65 enrolled in the National Health and Aging Trends Study in 2011, linked to Medicare claims data, including individuals living in subsidized housing and the general community. Participants were followed annually through 2020. Outcomes were hospitalization, short-term skilled nursing facility (SNF) utilization, long-term care utilization, and death. Fine-Gray competing risks regression analysis was used to assess the association of subsidized housing residence with hospitalization and nursing facility utilization, and Cox proportional hazards regression analysis was used to assess the association with death. Among 6294 participants (3600 women, 2694 men; mean age, 75.5 years [SD, 7.0]), 295 lived in subsidized housing at baseline and 5999 in the general community. Compared to older adults in the general community, those in subsidized housing had a higher adjusted subdistribution hazard ratio [sHR] of hospitalization (sHR 1.21; 95% CI, 1.03-1.43), short-term SNF utilization (sHR 1.49; 95% CI, 1.15-1.92), and long-term care utilization (sHR 2.72; 95% CI, 1.67-4.43), but similar hazard of death (HR, 0.86; 95% CI, 0.69-1.08). Individuals with functional impairment had a higher adjusted subdistribution hazard of hospitalization and short-term SNF utilization and individuals with dementia and functional impairment had a higher hazard of long-term care utilization. Older adults living in subsidized housing have higher hazards of hospitalization and nursing facility utilization compared to those in the general community. Housing-based interventions to optimize aging in place and mitigate risk of nursing facility utilization should consider risk factors including functional impairment and dementia.

Association between postoperative radiotherapy for young-onset nonsmall cell lung cancer and risk of second primary malignancies: comparative study.

The most common form of therapy for nonsmall cell lung cancer (NSCLC) in early stage is surgery-based combination therapy, including radiotherapy and immunotherapy. However, postoperative radiotherapy (PORT) of cancer is correlated with increasing risk of second primary malignancy (SPM), especially young-onset cancer cases. The authors aimed to quantify the risks of SPM associated with PORT treatment for young‑onset NSCLC in early stage. The authors screened for SPM that developed over 5 years since the diagnosis of NSCLC. Using the data from the Surveillance, Epidemiology, and End Results database, PORT-correlated risks were estimated with multivariate Logistic regression analysis. Moreover, Fine-Gray's competing risk regression analysis was used to calculate the cumulative incidence of SPMs. Among the 30308 young-onset NSCLC patients in early stage undergoing surgery, a total of 3728 patients have received PORT. Logistic regression analyses showed that PORT showed substantial correlation with elevated risks of second solid malignancies [relative risks (RR)=1.31; 95% CI: 1.17-1.46], lung cancer (RR=1.23; 95% CI: 1.07-1.42), breast cancer (RR=1.74; 95% CI: 1.16-2.74), and colon and rectum cancers (RR=1.37; 95% CI: 1.07-2.06) as well as a negligible risk of second hematologic malignancies (RR=1.15; 95% CI: 0.82-1.67). The cumulative incidence of SPMs revealed similar findings. Higher RR was obtained in NSCLC patients aged 60-69 years (RR=1.33), in white race (RR=1.36), diagnosed in 1975-2000 (RR=1.23) and 2001-2015 (RR=1.40), or diagnosed with lung adenocarcinoma (RR=1.55). PORT for young-onset NSCLC in early stage was correlated with elevated risks of SPMs (lung cancer, breast cancer, as well as colon and rectum cancers), supporting the need for long-term surveillance of these patients.

Impact of Multidomain Frailty on the Mode of Death in Older Patients With Heart Failure: A Cohort Study.

Although frailty is strongly associated with mortality in patients with heart failure (HF), the risk of which specific cause of death is associated with being complicated with frailty is unclear. We aimed to clarify the association between multidomain frailty and the causes of death in elderly patients hospitalized with HF. We analyzed data from the FRAGILE-HF cohort, where patients aged 65 years and older, hospitalized with HF, were prospectively registered between 2016 and 2018 in 15 Japanese hospitals before discharge and followed up for 2 years. All patients were assessed for physical, social, and cognitive dysfunction, and categorized into 3 groups based on their number of frailty domains (FDs, 0-1, 2, and 3). Kaplan-Meier survival analysis was used to evaluate the association between the number of FDs and all-cause mortality, whereas Fine-Gray competing risk regression analysis was used for assessing the impact on cause-specific mortality. We analyzed 1181 patients with HF (81 years old in median, 57.4% were male), 530 (44.9%), 437 (37.0%), and 214 (18.1%) of whom were categorized into the FD 0 to 1, FD 2, and FD 3 groups, respectively. During the 2-year follow-up, 240 deaths were observed (99 HF deaths, 34 cardiovascular deaths, and 107 noncardiovascular deaths), and an increase in the number of FD was significantly associated with mortality (Log-rank: P<0.001). The Fine-Gray competing risk analysis adjusted for age and sex showed that FDs 2 (subdistribution hazard ratio, 1.77 [95% CI, 1.11-2.81]) and 3 (2.78, [95% CI, 1.69-4.59]) groups were associated with higher incidence of noncardiovascular death but not with HF and other cardiovascular deaths. Although multidomain frailty is strongly associated with mortality in older patients with HF, it is mostly attributable to noncardiovascular death and not cardiovascular death, including HF death. URL: https://www.clinicaltrials.gov; Unique identifier: UMIN000023929.

Acute Kidney Injury and Subsequent Kidney Failure With Replacement Therapy Incidence in Older Adults With Advanced CKD: A Cohort Study of US Veterans

Advanced age is a major risk factor for chronic kidney disease (CKD) development, which has high heterogeneity in disease progression. Acute kidney injury (AKI) hospitalization rates are increasing, especially among older adults. Previous AKI epidemiologic analyses have focused on hospitalized populations, which may bias results toward sicker populations. This study examined the association between AKI and incident kidney failure with replacement therapy (KFRT) while evaluating age as an effect modifier of this relationship. Retrospective cohort study. 24,133 Veterans at least 65 years old with incident CKD stage 4 from 2011 to2013. AKI, AKI severity, and age. KFRT and death. The Fine-Gray competing risk regression was used to model AKI and incident KFRT with death as a competing risk. A Cox regression was used to model AKI severity and death. Despite a nonsignificant age interaction between AKI and KFRT, a clinically relevant combined effect of AKI and age on incident KFRT was observed. Compared with our oldest age group without AKI, those aged 65-74 years with AKI had the highest risk of KFRT (subdistribution HR [sHR], 14.9; 95% CI, 12.7-17.4), whereas those at least 85 years old with AKI had the lowest (sHR, 1.71; 95% CI, 1.22-2.39). Once Veterans underwent KFRT, their risk of death increased by 44%. A 2-fold increased risk of KFRT was observed across all AKI severity stages. However, the risk of death increased with worsening AKI severity. Our study lacked generalizability, was restricted to ever use of medications, and used inpatient serum creatinine laboratory results to define AKI and AKI severity. In this national cohort, advanced age was protective against incident KFRT but not death. This is likely explained by the high frequency of deaths observed in this population (51.1%). Nonetheless, AKI and younger age are substantial risk factors for incident KFRT.

Later aorta operation after aortic valve replacement for bicuspid aortic valve

BackgroundWe investigated long-term outcomes, particularly later aorta operations and overall death in patients who underwent aortic valve replacement for bicuspid aortic valve without aortic surgery.MethodsBetween January 2002 and December 2022, 274 patients underwent aortic valve replacement for bicuspid aortic valve at our institution. Of them, 181 patients who did not undergo aortic surgery, in accordance with current guidelines, were analyzed retrospectively.ResultsThe median follow-up duration was 6.1 (2.0–10.6) years, and follow-up was completed in 97.8% of pateints. There were 3 patients (1.7%) who underwent later aorta operation during follow-up period. The cumulative later aorta operation rate at 10 years adjusting overall death as competing risk was 16.3%, and the estimated rates of freedom from overall death at 10 years was 83.7%. Fine-Gray competing risk regression model showed that aortic valve stenosis was only the predictor of later aorta operation (hazard ratio 8.477; p = 0.012). In multivariable Cox models, predictors of overall death were aortic valve stenosis (hazard ratio: 8.270, 95% confidence interval: 1.082–63.235; p = 0.042) and operation time (hazard ratio: 1.011, 95% confidence interval: 1.004–1.017; p = 0.002).ConclusionsPatients with bicuspid aortic valve with ascending aortic diameter less than 45 mm are at low risk of later aorta operation after isolated aortic valve replacement.

Association of multiparametric magnetic resonance imaging findings with oncologic outcomes in non-palpable localized prostate cancer.

281 Background: Multiparametric magnetic resonance imaging (mpMRI) is becoming increasingly integrated into the evaluation and medical decision making for localized prostate cancer. However, mpMRI findings have not been correlated with prostate cancer outcomes and therefore are not currently included in staging. The purpose of this study was to test the association between mpMRI detected extraprostatic extension with oncologic outcomes in patients with non-palpable prostate cancer. Methods: We used the Veterans Affairs Prostate Data Core to identify patients diagnosed with cT1N0M0 prostate cancer between 2000-2021 with an mpMRI prior to definitive treatment. We reviewed MRI reports to identify presence of extracapsular extension (MRI-T3a), seminal vesicle invasion (MRI-T3b), and adjacent organ invasion (MRI-T4). We assessed the impact of mpMRI findings on metastasis free survival with multivariable Fine-Gray competing-risks regression. Results: Overall, 3,142 veterans with cT1N0M0 prostate cancer were included. There were 1,411 (45%) Black patients. By clinical staging, 904 (29%) had low risk, 1,626 (52%) had intermediate risk, and 612 (19%) had high risk disease. The majority of patients were treated with radiation (N=2,267; 72%). There were 217 (7%) patients with MRI-T3a disease, 87 (3%) patients with MRI-T3b disease, and 26 (1%) patients with MRI-T4 disease. The median follow-up time was 5.4 years (90% CI, 1-13 years). The 5-year cumulative incidence of metastases for patients with low, intermediate, and high risk prostate cancer were 3% (95% CI, 2-4%), 7% (95% CI, 6-8%), and 15% (95% CI, 12-18%). The 5-year cumulative incidence of metastases for patients with MRI-T3a, MRI-T3b, and MRI-T4 disease were 15% (95% CI, 10-20%), 29% (95% CI, 29-39%), and 40% (95% CI, 13-66%). After controlling for age, race, risk stratification (which includes prostate specific antigen (PSA) and grade group), local therapy, and co-morbidities, the presence of MRI-T3a (HR 1.58, 95% CI 1.09-2.29, p=0.02), MRI-T3b (HR 3.38, 95% CI 2.31-4.95, p&lt;0.0001), and MRI-T4 disease (HR 4.47, 95% CI 2.32-8.62, p&lt;0.0001) were independently associated with worse metastasis free survival. Similar results were obtained with PSA and grade group as individual variables. Conclusions: Extraprostatic extension observed on mpMRI is independently prognostic of metastasis free survival in patients with non-palpable prostate cancer. mpMRI is a critical imaging modality that should be widely available for patients with prostate cancer, and studies are ongoing to define its role as a standard staging modality.

Competing risk nomogram predicting cause-specific mortality in older patients with testicular germ cell tumors.

Testicular germ cell tumor (TGCT) is the most common type of malignancy in young men, but rarely in older adults. We aimed to construct a competing risk model to predict the prognosis for older patients with TGCT. We collected TGCT patients aged 50 years or older diagnosed between 2004 and 2015 from the National Cancer Institute's Surveillance, Epidemiology, and End Results (SEER) database. We estimated the cumulative incidences of cause-specific death (CSD) and other causes of death and established a nomogram predicting cause-specific mortality in older patients with TGCT by Fine-Gray competing risk regression. The concordance index (C-index), calibration curves, area under the receiver operating characteristic curve (AUC), and decision analysis curves (DCA) were used to evaluate the differentiation, accuracy, and clinical significance of the nomogram. A total of 2,751 older TGCT patients were included in the study. The 3-, 5-, and 10-year cumulative incidences were 4.4, 5.0 and 6.1%, respectively, for cause-specific death, and 3.8, 6.2, 13.1%, respectively, for other causes of death. Predictors of cause-specific mortality in older TGCT included age, marital status, annual household income, histology, tumor size, stage and surgery. In the training and validation sets, the C-indexes were greater than 0.8, indicating that the nomogram had good discrimination. The AUC revealed the same result. The calibration curves showed good agreement between the predicted and observed results of the nomogram. DCA curves indicated that the nomogram had more clinical significance than the conventional American Joint Committee on Cancer (AJCC) staging. Based on the total nomogram score of each case, all patients were categorized into low-risk and high-risk groups, and risk categorization allowed the identification of cases with a high risk of death. We established a competing risk nomogram with good performance that may help clinicians accurately predict the prognosis of older TGCT patients.

The effect of proactive, interactive, two-way texting on 12-month retention in antiretroviral therapy: Findings from a quasi-experimental study in Lilongwe, Malawi.

Retaining clients on antiretroviral therapy (ART) is challenging, especially during the first year on ART. Mobile health (mHealth) interventions show promise to close retention gaps. We aimed to assess reach (who received the intervention?) and effectiveness (did it work?) of a hybrid two-way texting (2wT) intervention to improve ART retention at a large public clinic in Lilongwe, Malawi. Between August 2021-June 2023, in a quasi-experimental study, outcomes were compared between two cohorts of new ART clients: 1) those opting into 2wT who received automated, weekly motivation short messaging service (SMS) messages and response-requested appointment reminders; and 2) a matched historical cohort receiving standard of care (SoC). Reach was defined as "the proportion clients ≤6 months of ART initiation eligible for 2wT". 2wT effectiveness was assessed in time-to-event analysis. Retention was presented in a Kaplan-Meier plot and compared between 2wT and SoC using a log-rank test. The effect of 2wT on ART dropout (lost to follow-up or stopped ART) was estimated using Fine-Gray competing risk regression models, adjusting for sex, age and WHO HIV stage at ART initiation. Of 1,146 clients screened, 501 were eligible for 2wT, a reach of 44%. Lack of phone (393/645; 61%) and illiteracy (149/645; 23%) were the most common ineligibility reasons. Among 468 participants exposed to 2wT, 12-month probability of ART retention was 91% (95% CI: 88% - 94%) compared to 76% (95% CI: 72% - 80%) among 468 SoC participants (p<0.001). Compared to SoC, 2wT participants had a 65% lower hazard of ART dropout at any timepoint (sub-distribution hazard ratio 0.35, 95% CI: 0.24-0.51; p<0.001). 2wT did not reach all clients. For those who opted-in, 2wT significantly increased 12-month ART retention. Expansion of 2wT as a complement to other retention interventions should be considered in other low-resource, routine ART settings.