Competing Risk Regression Models Research Articles

Association of marital status with cardiovascular death risk in patients with lung cancer: A population-based study

BackgroundTo investigate the association of marital status on cardiovascular death risk in lung cancer patients. MethodsUsing data from the Surveillance, Epidemiology, and End Results (SEER) database in the United States from 2011 to 2015 (N = 118,293), the association between marital status and cardiovascular death (CVD) risk in patients with lung cancer was assessed by competing-risks regression models. ResultsUnmarried status was associated with increased risk of cardiovascular death in lung cancer patients [hazard ratio (HR) = 1.398, 95 % confidence interval (CI): 1.268–1.542], which remained significant even after adjusting for potential covariates (HR = 1.407, 95 % CI: 1.276–1.551). Further unmarried subgroups analysis showed that the different unmarried status were associated with increased cardiovascular death risk as follows: single (HR = 1.397, 95 % CI: 1.236–1.1.580), separated (HR = 1.630, 95 % CI: 1.153–2.305), divorced (HR = 1.318, 95 % CI: 1.158–1.500), and widowed (HR = 1.561, 95 % CI: 1.393–1.749). Further subgroup analysis by sex revealed that compared to male lung cancer patients with married, CVD risk was significant increased in their counterparts with widowed (adjusted HR = 1.509, 95 % CI: 1.291–1.764, P<0.001), single (adjusted HR = 1.361, 95 % CI: 1.168–1.585, P<0.001) and divorced (adjusted HR = 1.353, 95 % CI: 1.177–1.555, P<0.001) rather than those with separated. However, similar phenomena was only observed in female lung cancer patients with widowed (adjusted HR = 1.414, 95 % CI: 1.220–1.640, P<0.001) and single (adjusted HR = 1.438, 95 % CI: 1.195–1.730, P<0.001). ConclusionUnmarried status was associated with increased cardiovascular death risk in patients with lung cancer, which highlighted that more attention and humanistic/supportive care should be offered to unmarried lung cancer patients for improving the prognosis.

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.

Association of hepatitis B virus treatment with all-cause and liver-related mortality among individuals with HBV and cirrhosis: a population-based cohort study

We evaluated the association of hepatitis B virus (HBV) treatment with all-cause, and liver-related mortality among individuals with HBV and cirrhosis in British Columbia (BC), Canada. This analysis included people diagnosed with HBV and had cirrhosis in the BC Hepatitis Testers Cohort, including data on all individuals diagnosed with HBV from 1990 to 2015 in BC and integrated with healthcare administrative data. We followed people with cirrhosis from the first cirrhosis diagnosis date until death or December 31, 2020. We compared all-cause and liver related mortality between those who received treatment and those who did not. HBV treatment was considered a time-varying variable. We performed multivariable Cox proportional hazards model and competing risk regression models to assess the association of HBV treatment with all causes, and liver-related mortality respectively using inverse probability of treatment weighted population. Among 4962 individuals with HBV and cirrhosis, 48.1% received HBV treatment. Treated individuals had a median follow-up of 2.97 years, compared to 2.87 years for untreated individuals. The treated group was older (median age 57 vs 54 years), had higher proportion of treated of males [1802 (75.50%) vs 1766 (68.8%)], from urban area [2318 (97.2%) vs 2355 (91.8%)], and from East and South Asian ethnicity [1506 (63.1%) vs 709 (27.5%)] compared to untreated group. Untreated people experienced higher all-cause mortality (115.47 vs. 35.72 per 1000 person-years) and liver-related mortality (49.86 vs. 11.39 per 1000 person-years). Multivariable models showed that HBV treatment significantly lowered the risk of all-cause mortality (adjusted hazard ratio (aHR) 0.74; 95% CI: 0.65, 0.84) and liver-related mortality (adjusted subdistribution hazard ratio (asHR) 0.72; 95% CI: 0.58, 0.89) compared to untreated individuals. Among untreated individuals with HBV, those with HCV coinfection had a higher risk of both all-cause and liver-related mortality (aHR 1.57; 95% CI: 1.22, 2.04, and asHR 1.60; 95% CI: 1.25, 2.05, respectively). HBV treatment was associated with a significant reduction in all-cause and liver-related mortality among individuals with cirrhosis. The findings highlight the need for treatment among individuals with HBV related cirrhosis especially those with coinfection with hepatitis C virus. This work was supported by the BC Centre for Disease Control and the Canadian Institutes of Health Research (CIHR) [Grant # NHC-142832, PJT-156066, and SC1 -178736]. JDM has received doctoral fellowship from the Canadian Network on Hepatitis C (CanHepC). DJ has received Doctoral Research Award (#201910DF1-435705-64343) from the Canadian Institutes of Health Research (CIHR) and doctoral fellowship from the CanHepC. CanHepC is funded by a joint initiative of the Canadian Institutes of Health Research (CIHR) (NHC-142832) and the Public Health Agency of Canada (PHAC).

Second Primary Differentiated Thyroid Carcinoma in Adult Cancer Survivors: A SEER Database Analysis.

Adult cancer survivors are at a heightened risk for secondary primary differentiated thyroid carcinoma (2-DTC). The characteristics and outcomes of 2-DTC remain poorly understood. We aim to explore the characteristics and outcomes of 2-DTC. We retrospectively analyzed data from the SEER database (2000-2017). 2-DTC was divided into 25 subgroups based on the prior primary malignancies (PPMs). Baseline characteristics were compared using the Chi-square test. Multivariable logistic analysis was used to identified if PPMs associated with aggressive DTC characteristics. DTC-specific and cancer-specific mortality were analyzed using univariable and multivariable competing risk regression model. There were 138,555 1-DTC and 9,253 2-DTC patients were identified. 2-DTC patients were predominantly older, male, and white compared to first primary DTC (1-DTC) (all P < 0.05). In multivariable logistic regression analysis, only four types of PPMs were associated with higher rates of DTC aggressive characteristics, while 19 types exhibited lower rates (all P < 0.05). In multivariable competing risk analysis, 2-DTC showed no mortality risk in stages I (SHR: 1.16, 95% CI: 0.65-2.07) and II (SHR: 0.67, 95% CI: 0.45-1.01), but a protective role in stages III (SHR: 0.47, 95% CI: 0.27-0.83) and IV (SHR: 0.72, 95% CI: 0.52-0.99). Most PPMs that developed into 2-DTC had a lower risk of DTC-specific death than 1-DTC, but many PPMs had a higher risk of cancer-specific death. Given the characteristics and outcomes of 2-DTC, aggressive treatment for 2-DTC, particularly for PPM with a high mortality risk, may not be advisable.

Radiotherapy Versus Partial Penectomy for T1 Squamous Cell Carcinoma of the Penis.

Radiotherapy (RT) represents an alternative treatment option for patients with T1 squamous cell carcinoma of the penis (SCCP), with proven feasibility and tolerability. However, it has never been directly compared with partial penectomy (PP) using cancer-specific mortality (CSM) as an end point. In the Surveillance, Epidemiology, and End Results database (2000-2020), T1N0M0 SCCP patients treated with RT or PP were identified. This study relied on 1:4 propensity score-matching (PSM) for age at diagnosis, tumor stage, and tumor grade. Subsequently, cumulative incidence plots as well as multivariable competing risks regression (CRR) models addressed CSM. Additionally, the study accounted for the confounding effect of other-cause mortality (OCM). Of 895 patients with T1N0M0 SCCP, 55 (6.1%) underwent RT and 840 (93.9%) underwent PP. The RT and PP patients had a similar age distribution (median age, 70 vs 70 years) and more frequently harbored grade I or II tumors (67.3% vs 75.8%) as well as T1a-stage disease (67.3% vs 74.3%). After 1:4 PSM, 55 (100%) of the 55 RT patients versus 220 (26.2%) of the 840 PP patients were included in the study. The 10-year CSM derived from the cumulative incidence plots was 25.4% for RT and 14.4% for PP. In the multivariable CRR models, RT independently predicted a higher CSM than PP (hazard ratio, 1.99; 95% confidence interval, 1.05-3.80; p = 0.04). For the T1N0M0 SCCP patients treated in the community, RT was associated with nearly a twofold higher CSM than PP. Ideally, a validation study based on tertiary care institution data should be conducted to test whether this CSM disadvantage is operational only in the community or not.

Pancreatic Cancer Surveillance and Survival of High-Risk Individuals

Pancreatic ductal adenocarcinoma (PDAC) is a deadly disease with increasing incidence. The majority of PDACs are incurable at presentation, but population-based screening is not recommended. Surveillance of high-risk individuals for PDAC may lead to early detection, but the survival benefit is unproven. To compare the survival of patients with surveillance-detected PDAC with US national data. This comparative cohort study was conducted in multiple US academic medical centers participating in the Cancer of the Pancreas Screening program, which screens high-risk individuals with a familial or genetic predisposition for PDAC. The comparison cohort comprised patients with PDAC matched for age, sex, and year of diagnosis from the Surveillance, Epidemiology, and End Results (SEER) program. The Cancer of the Pancreas Screening program originated in 1998, and data collection was done through 2021. The data analysis was performed from April 29, 2022, through April 10, 2023. Endoscopic ultrasonography or magnetic resonance imaging performed annually and standard-of-care surgical and/or oncologic treatment. Stage of PDAC at diagnosis, overall survival (OS), and PDAC mortality were compared using descriptive statistics and conditional logistic regression, Cox proportional hazards regression, and competing risk regression models. Sensitivity analyses and adjustment for lead-time bias were also conducted. A total of 26 high-risk individuals (mean [SD] age at diagnosis, 65.8 [9.5] years; 15 female [57.7%]) with PDAC were compared with 1504 SEER control patients with PDAC (mean [SD] age at diagnosis, 66.8 [7.9] years; 771 female [51.3%]). The median primary tumor diameter of the 26 high-risk individuals was smaller than in the control patients (2.5 [range, 0.6-5.0] vs 3.6 [range, 0.2-8.0] cm, respectively; P < .001). The high-risk individuals were more likely to be diagnosed with a lower stage (stage I, 10 [38.5%]; stage II, 8 [30.8%]) than matched control patients (stage I, 155 [10.3%]; stage II, 377 [25.1%]; P < .001). The PDAC mortality rate at 5 years was lower for high-risk individuals than control patients (43% vs 86%; hazard ratio, 3.58; 95% CI, 2.01-6.39; P < .001), and high-risk individuals lived longer than matched control patients (median OS, 61.7 [range, 1.9-147.3] vs 8.0 [range, 1.0-131.0] months; 5-year OS rate, 50% [95% CI, 32%-80%] vs 9% [95% CI, 7%-11%]). These findings suggest that surveillance of high-risk individuals may lead to detection of smaller, lower-stage PDACs and improved survival.

Time-varying effect in older patients with early-stage breast cancer: a model considering the competing risks based on a time scale.

Patients with early-stage breast cancer may have a higher risk of dying from other diseases, making a competing risks model more appropriate. Considering subdistribution hazard ratio, which is used often, limited to model assumptions and clinical interpretation, we aimed to quantify the effects of prognostic factors by an absolute indicator, the difference in restricted mean time lost (RMTL), which is more intuitive. Additionally, prognostic factors of breast cancer may have dynamic effects (time-varying effects) in long-term follow-up. However, existing competing risks regression models only provide a static view of covariate effects, leading to a distorted assessment of the prognostic factor. To address this issue, we proposed a dynamic effect RMTL regression that can explore the between-group cumulative difference in mean life lost over a period of time and obtain the real-time effect by the speed of accumulation, as well as personalized predictions on a time scale. A simulation validated the accuracy of the coefficient estimates in the proposed regression. Applying this model to an older early-stage breast cancer cohort, it was found that 1) the protective effects of positive estrogen receptor and chemotherapy decreased over time; 2) the protective effect of breast-conserving surgery increased over time; and 3) the deleterious effects of stage T2, stage N2, and histologic grade II cancer increased over time. Moreover, from the view of prediction, the mean C-index in external validation reached 0.78. Dynamic effect RMTL regression can analyze both dynamic cumulative effects and real-time effects of covariates, providing a more comprehensive prognosis and better prediction when competing risks exist.

Incidence, Characteristics and Survival Rates of Bladder Cancer after Rectosigmoid Cancer Radiation.

Historical external beam radiation therapy (EBRT) for rectosigmoid cancer (RCa) predisposed patients to an increased risk of secondary bladder cancer (BCa). However, no contemporary radiotherapy studies are available. We addressed this knowledge gap. Within the Surveillance, Epidemiology, and End Results database (2000-2020), we identified non-metastatic RCa patients who either underwent radiotherapy (EBRT+) or did not (EBRT-). Cumulative incidence plots and multivariable competing risk regression models (CRR) were fitted to address rates of BCa after RCa. In the subgroup of BCa patients, the same methodology addressed BCa-specific mortality (BCSM) according to EBRT exposure status. Of the 188,658 non-metastatic RCa patients, 54,562 (29%) were EBRT+ vs. 134,096 (73%) who were EBRT-. In the cumulative incidence plots, the ten-year BCa rates were 0.7% in EBRT+ vs. 0.7% in EBRT- patients (p = 0.8). In the CRR, EBRT+ status was unrelated to BCa rates (multivariable HR: 1.1, p = 0.8). In the subgroup of 1416 patients with BCa after RCa, 443 (31%) were EBRT+ vs. 973 (69%) who were EBRT-. In the cumulative incidence plots, the ten-year BCSM rates were 10.6% in EBRT+ vs. 12.1% in EBRT- patients (p = 0.7). In the CRR, EBRT+ status was unrelated to subsequent BCSM rates (multivariable HR: 0.9, p = 0.9). Although historical EBRT for RCa predisposed patients to higher BCa rates, contemporary EBRT for RCa is not associated with increased subsequent BCa risk. Moreover, in patients with BCa after RCa, exposure to EBRT does not affect BCSM.

Predictive value of the controlling nutritional status (CONUT) score to assess long-term mortality (10 Years) in patients with hypertension

Background and aimsMalnutrition is associated with poor outcomes in patients with chronic diseases. Aim of this study is to investigate the prevalence of malnutrition in patients with hypertension and relationship between malnutrition severity and long-term mortality in these patients. Methods and resultThe study included 11,278 patients with hypertension from the National Health and Nutrition Examination Survey database. The degree of malnutrition was assessed using the Controlled Nutritional Status score, with patients divided into normal, mild, and moderate-to-severe groups. After 10 years of follow-up, the results showed that patients who died had higher CONUT scores, poorer nutritional status, and lower albumin, total cholesterol, and lymphocyte counts than those who survived (P < 0.05). The Kaplan–Meier analysis revealed that patients with poor nutritional status had a significantly higher risk of all-cause death. In the Non-Lipid Lowering Drugs group, the CONUT score (hazard ratio (HR): 1.225; 95% confidence interval (CI): 1.162–1.292; P < 0.0001), as well as mild (HR: 1.532; 95% CI 1.340–1.751; P < 0.0001) and moderate-to-severe malnutrition (HR: 2.797; 95% CI: 1.441–5.428; P = 0.0024), were independent predictors of long-term mortality. The competing risk regression models showed that cardiovascular and cerebrovascular mortality increased with increasing CONUT scores. The results were robust in both subgroup and sensitivity analyses. ConclusionMalnutrition significantly impacts long-term mortality in hypertensive patients. The CONUT score may be a useful tool for assessing the nutritional status of patients with hypertension in the non-lipid-lowering population and for predicting their long-term mortality.

Constructing a prognostic model for colorectal cancer with synchronous liver metastases after preoperative chemotherapy: a study based on SEER and an external validation cohort.

The combination of preoperative chemotherapy and surgical treatment has been shown to significantly enhance the prognosis of colorectal cancer with liver metastases (CRLM) patients. Nevertheless, as a result of variations in clinicopathological parameters, the prognosis of this particular group of patients differs considerably. This study aimed to develop and evaluate Cox proportional risk regression model and competing risk regression model using two patient cohorts. The goal was to provide a more precise and personalized prognostic evaluation system. We collected information on individuals who had a pathological diagnosis of colorectal cancer between 2000 and 2019 from the Surveillance, Epidemiology, and End Results (SEER) Database. We obtained data from patients who underwent pathological diagnosis of colorectal cancer and got comprehensive therapy at the hospital between January 1, 2010, and June 1, 2022. The SEER data collected after screening according to the inclusion and exclusion criteria were separated into two cohorts: a training cohort (training cohort) and an internal validation cohort (internal validation cohort), using a random 1:1 split. Subgroup Kaplan-Meier (K-M) survival analyses were conducted on each of the three groups. The data that received following screening from the hospital were designated as the external validation cohort. The subsequent variables were chosen for additional examination: age, gender, marital status, race, tumor site, pretreatment carcinoembryonic antigen level, tumor size, T stage, N stage, pathological grade, number of tumor deposits, perineural invasion, number of regional lymph nodes examined, and number of positive regional lymph nodes. The primary endpoint was median overall survival (mOS). In the training cohort, we conducted univariate Cox regression analysis and utilized a stepwise regression approach, employing the Akaike information criterion (AIC) to select variables and create Cox proportional risk regression models. We evaluated the accuracy of the model using calibration curve, receiver operating characteristic curve (ROC), and area under curve (AUC). The effectiveness of the models was assessed using decision curve analysis (DCA). To evaluate the non-cancer-related outcomes, we analyzed variables that had significant impacts using subgroup cumulative incidence function (CIF) and Gray's test. These analyses were used to create competing risk regression models. Nomograms of the two models were constructed separately and prognostic predictions were made for the same patients in SEER database. This study comprised a total of 735 individuals. The mOS of the training cohort, internal validation cohort, and QDU cohort was 55.00months (95%CI 46.97-63.03), 48.00months (95%CI 40.65-55.35), and 68.00months (95%CI 54.91-81.08), respectively. The multivariate Cox regression analysis revealed that age, N stage, presence of perineural infiltration, number of tumor deposits and number of positive regional lymph nodes were identified as independent prognostic risk variables (p < 0.05). In comparison to the conventional TNM staging model, the Cox proportional risk regression model exhibited a higher C-index. After controlling for competing risk events, age, N stage, presence of perineural infiltration, number of tumor deposits, number of regional lymph nodes examined, and number of positive regional lymph nodes were independent predictors of the risk of cancer-specific mortality (p < 0.05). We have developed a prognostic model to predict the survival of patients with synchronous CRLM who undergo preoperative chemotherapy and surgery. This model has been tested internally and externally, confirming its accuracy and reliability.

Cost effective utilization of apheresis for stem cell transplantation in multiple myeloma.

e19528 Background: Salvage autologous stem cell transplantation (ASCT) is an effective and feasible treatment option for patients with relapsed multiple myeloma (MM). It is standard practice to collect stem cells adequate for two transplants for ASCT eligible patients with newly diagnosed MM (NDMM). Stem cell collection is an expensive procedure due to the cost of granulocyte-colony stimulating factor, plerixafor, apheresis, chemotherapy in select cases and finally cryopreservation. However, the rate of utilization of second ASCT is not known. Methods: We conducted a single institution, retrospective study of 511 consecutive patients with NDMM who underwent ASCT to identify the proportion of patients receiving second ASCT. Patients received ASCT as front-line therapy between 1/1/2015-2/13/2019. Demographic and disease characteristics were summarized using median and range for continuous variables, and frequency and percentages were calculated for categorical variables. The cumulative incidence of second ASCT was estimated using the Fine and Gray method, and competing risk regression models were used to estimate the hazard ratios for risk of second ASCT. All statistical tests were two-sided with a type 1 error of &lt; 0.05 indicating statistical significance. All estimates were reported with 95% confidence intervals (95% CI). Results: At a median follow-up of 4.7 years, 25 out of 511 patients received a second ASCT. The cumulative incidence rate at 5 years was 2.6% (95% CI 1.4-4.4%).Age at diagnosis, age at first ASCT and Charlson comorbidity index (CMI) were significantly associated with the risk of second ASCT in univariable analysis (UVA). In multivariable analysis (MVA) age at first ASCT was the only factor that was predictive of a second ASCT. We devised a predictive score for utilization of second ASCT using hazard ratios for each of the three significant factors noted in the UVA. Scoring was done as follows: age &lt; 65 years – 1 point, &gt; 65 years – 7 points; 1 point for CMI 0-1, 2 points for CMI 2 or higher; serum creatinine ≤1.2 – 1 point, &gt; 1.2 – 3 points. Based on the total score, patients are grouped into low ( &lt; = 3), medium (4-6) and high (7+) likelihood categories, with cumulative incidence rates of receiving second ASCT at 4.0% (95% CI: 1.3-9.1%), 3.4% (95% CI 1.4-7.0%) and 0.6% (95% CI 0.1-3.1%) respectively. Patients older than 65 years were 87% less likely to receive a second ASCT compared with those younger than 65 years (HR = 0.13, 95% CI 0.02-0.98). Conclusions: Using this predictive score, goal of stem cell collection for patients with MM could be determined more efficiently. This could avoid extra days of apheresis, chemo mobilization, hospitalizations and need for cryopreservation at least for patients with a low likelihood of second ASCT, translating into cost effective utilization of resources. We plan to validate this score prospectively in a larger group of patients with NDMM undergoing ASCT in the future.

Type III Endoleak Incidence and Outcomes in Endovascular Aortic Repair: Comparison of Anatomical and Proximal Fixation Devices.

To evaluate the influence of endograft fixation type on the incidence, treatment, and outcomes of type III endoleaks (TIIIELs). Abdominal aortic aneurysms (AAAs) treated with bifurcated endografts between 1994 and 2020 were prospectively collected and reviewed. The endograft included were classified as "Anatomical Fixation" (AF) (Powerlink [Endologix] and AFX [Endologix]) or "Proximal Fixation" (PF). The primary outcome was the incidence of TIIIEL over time, stratified by fixation type. Secondary outcomes included between-group comparisons of baseline characteristics, intraoperative details during TIIIEL correction, and survival analysis after TIIIEL diagnosis. A total of 2065 endovascular aneurysm repairs were performed: 872 (42.2%) with AF and 1193 (57.8%) with PF devices. The estimated incidence of TIIIEL at 1, 5, and 10 years was 0.4%, 4.2%, and 7.3%, and 0.5%, 3.2%, and 4.6% for AF and PF, respectively (p=0.157), and fixation type was not associated with TIIIEL development in the competing risk regression model (p=0.101). The cumulative overall survival rate in patients diagnosed with TIIIEL did not differ significantly between the groups (p=0.077). The rate of recurrent TIIIELs was significantly lower in the AF group (7.1% vs 22.7%; p=0.044); however, no significant difference was found in secondary reintervention between the two groups (11.9% vs 27.3%, p=0.074). Patients with angulated and calcified aortic neck (SHR 3.4, 95% CI 1.2-9.6, p=0.022) and larger aneurysms (SHR 1.2; 95% CI 1.1-1.3; p<0.001) had a higher risk of TIIIEL. Likewise, the use of three or more endograft components increased the risk of TIIIEL by 3.1 times (SHR 3.1; 95% CI 1.7-5.4; p<0.001). The occurrence of TIIIELs was not affected by the type of endograft fixation. For larger abdominal aortic aneurysms (AAAs) and aneurysms with angulated and calcified aortic necks, there is a higher likelihood of developing TIIIELs during follow-up, regardless of the endograft type used. The type of fixation does not influence the incidence of TIII ELs. EVAR in larger AAAs and aneurysms with angulated and calcified aortic necks have a higher risk of developing TIII EL. Moreover, the risk of TIII EL is considerably increased by the use of three or more modular components.

Association of diabetic retinopathy on all-cause and cause-specific mortality in older adults with diabetes: National Health and Nutrition Examination Survey, 2005–2008

To evaluate the effect of diabetic retinopathy (DR) status or severity on all-cause and cause-specific mortality among diabetic older adults in the United States using the most recent National Health and Nutrition Examination Survey (NHANES) follow-up mortality data. The severity of DR was graded according to the Early Treatment Diabetic Retinopathy Study (ETDRS) grading scale. Multiple covariate-adjusted Cox proportional hazards regression models, Fine and Gray competing risk regression models, and propensity score matching (PSM) methods were used to assess the risk of all-cause and cause-specific mortality in individuals with diabetes. All analyses adopted the weighted data and complex stratified design approach proposed by the NHANES guidelines. Time to death was calculated based on the time between baseline and date of death or December 31, 2019, whichever came first. Ultimately 1077 participants, representing 3,025,316 US non-hospitalized individuals with diabetes, were included in the final analysis. After a median follow-up of 12.24 years (IQR, 11.16–13.49), 379 participants were considered deceased from all-causes, with 43.90% suffering from DR, including mild DR (41.50%), moderate to severe DR (46.77%), and proliferative DR (PDR) (67.21%). DR was associated with increased all-cause, cardiovascular disease (CVD) and diabetes mellitus (DM)-specific mortality, which remained consistent after propensity score matching (PSM). Results of DR grading assessment suggested that the presence of mild, moderate to severe NPDR was significantly associated with increased risk of all-cause and CVD-specific mortality, while the presence and severity of any DR was associated with increased DM-specific mortality, with a positive trend. The presence of DR in elderly individuals with diabetes is significantly associated with the elevated all-cause and CVD mortality. The grading or severity of DR may reflect the severity of cardiovascular disease status and overall mortality risk in patients with diabetes.

Laparoscopic Spleen-Preserving Hilar Lymphadenectomy for Advanced Proximal Gastric Cancer Without Greater Curvature Invasion

Splenic hilar lymphadenectomy has been recommended for locally advanced proximal gastric cancer (APGC) involving the greater curvature. However, it is unclear whether laparoscopic spleen-preserving splenic hilar lymphadenectomy (LSPSHL) is associated with a long-term survival benefit for APGC without greater curvature invasion. To present the 5-year follow-up data from a randomized clinical trial that compared laparoscopic total gastrectomy (D2 group) with D2 plus LSPSHL (D2 + No. 10 group) among patients with resectable APGC. This is a post hoc secondary analysis of a randomized clinical trial that enrolled 536 patients with potentially resectable APGC (cT2-4a, N0 or N+, and M0) without greater curvature invasion from January 5, 2015, to October 10, 2018. All patients were tracked for at least 5 years. The final follow-up was on October 30, 2023. Patients were randomly assigned in a 1:1 ratio to the D2 + No. 10 or D2 groups. The 5-year disease-free survival (DFS) and overall survival (OS) rates were measured. Recurrence patterns and causes of death were compared. A total of 526 patients (392 men [74.5%]; mean [SD] age, 60.6 [9.6] years) were included in the modified intent-to-treat analysis, with 263 patients in each group. The 5-year DFS rate was 63.9% (95% CI, 58.1%-69.7%) for the D2 + No. 10 group and 55.1% (95% CI, 49.1%-61.1%) for the D2 group (log-rank P = .04). A statistically significant difference was observed in the 5-year OS between the D2 + No. 10 group and the D2 group (66.2% [95% CI, 60.4%-71.9%] vs 57.4% [95% CI, 51.4%-63.4%]; log-rank P = .03). The No. 10 lymph node exhibited a therapeutic value index (TVI) of 6.5, surpassing that of Nos. 8a (TVI, 3.0), 11 (TVI, 5.8), and 12a (TVI, 0.8). A total of 86 patients in the D2 + No. 10 group (cumulative incidence, 32.7%) and 111 patients in the D2 group (cumulative incidence, 42.2%) experienced recurrence (hazard ratio, 0.72; 95% CI, 0.54-0.95; P = .02). The multivariable competing risk regression model demonstrated that D2 + No. 10 remained an independent protective factor for a lower 5-year cumulative recurrence rate after surgery (hazard ratio, 0.75; 95% CI, 0.56-1.00; P = .05). There was a significant difference in the 5-year cumulative recurrence rate at the No. 10 lymph node area between the 2 groups (D2 + No. 10 group vs D2 group: 0% vs 2.3% [n = 6]; P = .01). This post hoc secondary analysis of a randomized clinical trial found that laparoscopic total gastrectomy with LSPSHL can improve the prognosis and reduce recurrence for APGC without greater curvature invasion. Future multicenter studies are warranted to validate these findings. ClinicalTrials.gov Identifier: NCT02333721.

Association of serum 25-hydroxy-vitamin D concentration and risk of mortality in cancer survivors in the United States

PurposeCancer survivors have a high risk of mortality, and vitamin D (VD) is associated with the risk of mortality. This study is aim to examine the impact of VD on mortality in cancer survivors.MethodsA prospective study was conducted using data from the National Health and Nutrition Examination Survey. Participants were obtained information on their baseline characteristics, dietary habits, comorbidities, lifestyle, and serum 25-hydroxy VD [25(OH)D] concentrations. The weighted Cox proportional hazard and competing risk regression models were used to estimate the hazard ratio and 95% confidence intervals (HR, 95% CI) of mortality for different serum 25(OH)D concentrations. Restricted cubic spline (RCS) curves were utilized to illustrate the dose–response relationship between serum 25(OH)D concentrations and mortality.ResultsThe study encompassed 2,495 participants with cancer diagnoses. Multivariate models indicated that, compared to serum 25(OH)D concentrations below 58.5 nmol/L, concentrations exceeding 81.6 nmol/L were associated with reduced HRs for all-cause mortality (HR = 0.70; 95% CI: 0.56–0.87), cardiovascular mortality (HR = 0.53; 95% CI: 0.32–0.86), and cancer-specific mortality (HR = 0.66; 95% CI: 0.45–0.99). RCS curves revealed “L-shaped” associations between serum 25(OH)D concentration and both all-cause and cancer-specific mortality, with threshold effects at 87.9 nmol/L and 84.6 nmol/L, respectively. Conversely, the relationship between serum 25(OH)D concentration and cardiovascular mortality exhibited a more linear pattern, with a threshold at 88.7 nmol/L. Subgroup analyses highlighted a gender-specific interaction that elevated serum 25(OH)D concentrations were significantly more protective against mortality in males than in females, especially regarding cancer-specific mortality (P-interaction = 0.009).ConclusionElevated serum 25(OH)D concentrations were correlated with decreased risks of all-cause, cardiovascular, and cancer-specific mortality in cancer survivors, with benefit thresholds at 87.9, 88.7, and 84.6 nmol/L, respectively. These findings suggested that cancer survivors might benefit from higher vitamin D recommendations than the general population.

Comorbidities, mortality and metabolic profile in individuals with primary biliary cholangitis-A Phenome-Wide-Association-Study.

Primary biliary cholangitis (PBC) is a chronic, immune-mediated liver disease that can lead to fibrosis and cirrhosis. In this cohort study, we aimed to investigate morbidity and mortality in conjunction with metabolomic changes of PBC in a UK population-based cohort. 454 participants with PBC and 908 propensity score (age, sex, BMI, ethnicity) matched controls without liver disease were included in the study. A subset of participants with PBC and controls were analysed for their metabolomic profile. Further, PBC-associated comorbidities were investigated by PheWAS analysis. Lastly, we assessed causes of death in individuals with PBC using a Fine and Grey competing-risks regression model. Compared to the control group, various pathways associated with the metabolism of amino acids, lipids, and liver biochemistry were significantly enriched in individuals with PBC. We found reduced levels of S-HDL-cholesterol and Glycoprotein Acetyls in individuals with PBC as well as an association with diseases of the circulatory system. Notably, PBC individuals had a higher prevalence of digestive diseases, autoimmune diseases, cardiovascular diseases, anaemias, mental disorders, and urinary tract infections compared to the control group. Strikingly, the overall mortality was almost three times higher in the PBC group compared to the control group, with diseases of the digestive system accounting for a significant elevation of the death rate. A subsequent analysis, enhanced by propensity score matching that included the APRI score, demonstrated that the observed morbidity could not be exclusively attributed to advanced hepatic disease. Our study provides a detailed perspective on the morbidity of individuals with PBC. The exploration of potential effects of disease state on morbidity suggest that early detection and early treatment of PBC could enhance patient prognosis and prevent the onset of comorbid diseases. Finally, the metabolomic alterations could represent a link between the pathophysiological processes underlying PBC development, progression, and associated morbidity.

Effects of restrictive fluid therapy on the time to resolution of hyperlactatemia in ICU patients with septic shock. A secondary post hoc analysis of the CLASSIC randomized trial

PurposeThe aim of this study was to examine the effects of intravenous (IV) fluid restriction on time to resolution of hyperlactatemia in septic shock. Hyperlactatemia in sepsis is associated with worse outcome. Sepsis guidelines suggest targeting lactate clearance to guide fluid therapy despite the complexity of hyperlactatemia and the potential harm of fluid overload.MethodsWe conducted a post hoc analysis of serial plasma lactate concentrations in a sub-cohort of 777 patients from the international multicenter clinical CLASSIC trial (restriction of intravenous fluids in intensive care unit (ICU) patients with septic shock). Adult ICU patients with septic shock had been randomized to restrictive (n = 385) or standard (n = 392) intravenous fluid therapy. The primary outcome, time to resolution of hyperlactatemia, was analyzed with a competing-risks regression model. Death and discharge were competing outcomes, and administrative censoring was imposed 72 h after randomization if hyperlactatemia persisted. The regression analysis was adjusted for the same stratification variables and covariates as in the original CLASSIC trial analysis.ResultsThe hazard ratios (HRs) for the cumulative probability of resolution of hyperlactatemia, in the restrictive vs the standard group, in the unadjusted analysis, with time split, were 0.94 (confidence interval (CI) 0.78–1.14) at day 1 and 1.21 (0.89–1.65) at day 2–3. The adjusted analyses were consistent with the unadjusted results.ConclusionIn this post hoc retrospective analysis of a multicenter randomized controlled trial (RCT), a restrictive intravenous fluid strategy did not seem to affect the time to resolution of hyperlactatemia in adult ICU patients with septic shock.

Association of diabetes mellitus with dementia- and non-dementia-related mortality amongst women: a secondary competing risks analysis of the California Teachers Study.

The prevalence of dementia is rapidly increasing. Attempts to further understand modifiable risk factors such as diabetes mellitus (DM) are urgently needed to inform public health policies for prevention. Thus, the objective of the current study was to assess the relationship between DM and risk of dementia and non-dementia mortality amongst women in the California Teachers Study prospective cohort. Women (n = 124,509) aged 22-104 years at baseline were included. DM was ascertained from self-reported questionnaires and hospital-linked records. Dementia-related deaths were ascertained from state and national records. Competing risk regression models were used to estimate cause-specific hazard ratios and 95% confidence intervals for the association of DM with dementia- and non-dementia-related mortality. There were 10,511 total DM cases and 3625 deaths due to dementia over a mean of 21.3 years of follow-up. Fully adjusted cause-specific hazard ratios of the association with DM were 2.26 (2.01, 2.55) for dementia-related and 1.97 (1.89, 2.05) for the competing risk of non-dementia-related mortality. This association was strongest amongst participants with incident DM, younger age at baseline and higher alcohol consumption or who were overweight. In the California Teachers Study, women with DM had increased risk of mortality due to both dementia and non-dementia causes; however, the risk of mortality due to dementia was elevated compared to non-dementia causes only amongst participants with incident DM.

Direct oral anticoagulant-associated bleeding complications in patients with gastrointestinal cancer and venous thromboembolism

BackgroundDirect oral anticoagulants (DOACs) have become widely used for cancer-associated venous thromboembolism (VTE). However, DOAC-associated bleeding complications remain challenging, especially in patients with gastrointestinal (GI) cancer. This study aimed to compare the bleeding outcomes between patients with upper or lower GI cancers and those without GI cancer. MethodsUsing the COMMAND VTE Registry-2 database, which is a multicenter registry enrolling 5197 consecutive acute symptomatic VTE patients among 31 centers in Japan between January 2015 and August 2020, we identified 1149 active cancer patients with DOACs (upper GI cancer: N=88; lower GI cancer: N=114; non-GI cancer: N=947). The primary outcome was major bleeding during anticoagulation therapy, which was evaluated in the competing risk regression model. ResultsThe upper GI cancer group had a lower mean body weight, and most often had anemia. The cumulative 5-year incidence of major bleeding was higher in the upper GI cancer group (upper GI cancer: 22.4%, lower GI cancer: 15.4%, and non-GI cancer: 11.6%, P=0.015). The most frequent major bleeding site in the upper GI cancer group was the upper GI (53%), followed by the lower GI (24%). After adjusting for the confounders, the excess risk in upper GI cancer relative to non-GI cancer remained significant for major bleeding (adjusted subhazard ratio, 2.25; 95%CI, 1.31-3.87, P=0.003), but that in lower GI cancer was insignificant. ConclusionsUpper GI cancer, but not lower GI cancer, as compared to non-GI cancer was associated with a higher risk for major bleeding during anticoagulation therapy with DOACs.Clinical Trial Registration: URL: http://www.umin.ac.jp/ctr/index.htmUnique identifier: UMIN000044816.

Health-related quality of life after minimal-invasive treatment of aortic valve stenosis in the elderly.

Although transfemoral transcatheter aortic valve implantation (TF-TAVI) offers superior early outcome over open surgical aortic valve replacement (SAVR) in the elderly, a comparison of TF-TAVI with surgery performed through partial upper mini sternotomy (PUMS) hasn't yet been validated. The aim of the present study is to evaluate the clinical outcome and quality of life of patients subjected to TF-TAVI and open surgical aortic valve replacement through partial upper mini sternotomy (PUMS-SAVR). Baseline, procedural and post-treatment data of 197 consecutive patients: 137 TF-TAVI and 60 PUMS-SAVR treated at Philipps University of Marburg, were retrospectively collected. The propensity score method was used to create two groups in a 1:1 fashion. Questionnaire assessment (SF36_LQ) of quality of life of the matched patients was carried out at the ambulant routine control presentation. A competing risk regression model is used to evaluate the impact of the clinical outcome on health-related quality of life (HrQoL). After propensity matching, TF-TAVI remained associated with lower procedural time (136±50 vs. 298±36 min, P<0.01), intensive care unit stay (2.68±2.70 vs. 4.29±2.43 days, P<0.01), transfusion of packed red cell units (0.46±2.05 vs. 1.60±2.00 U, P=0.02) and higher heart block (42.86% vs. 0%, P<0.01) and permanent pacemaker implantation rates (14.29% vs. 0%, P=0.05) compared to PUMS-SAVR. TF-TAVI is associated with less complains, superior HrQoL (excellent 40% and very good 60% vs. very good 100% in PUMS). Partial sternotomy is the main predictor of the inferior HrQoL, with the regression coefficient of -1.11 (95% confidential interval, -1.503 to -0.726; R2=0.324, P<0.0001). Transfusion (P=0.26), paravalvular leakage (0.618), pacemaker implantation (P=0.19) and delirium (P=0.92) did not influence HrQoL after the minimal-invasive treatment of aortic valve stenosis in elderly patients. Although PUMS-SAVR offers better technical outcomes with less permanent pacemaker implantation and less paravalvular leakage than TF-TAVI, it is still associated with more need for transfusion, longer ventilation-and intensive care unit-times, and prolonged hospital stay. In the elderly, PUMS-SAVR achieves inferior quality of life compared to TF-TAVI. Partial sternotomy reveals as the strongest risk factor of perceived health-level post-treatment. It remains to be revealed whether fast-track open heart surgery that maintains a fully intact sternum and allows immediate postoperative extubation-as performed through video-assisted mini-thoracotomy or thoracoscopic robotic procedures with percutaneous cannulation - should be favored against PUMS-SAVR.