Multivariate Cox Proportional-hazards Regression Models Research Articles

Time to recovery from necrotizing enterocolitis and its predictors among neonates admitted to Neonatal Intensive Care Unit in Bahir Dar, Ethiopia: A retrospective follow up study, 2022.

Necrotizing enterocolitis is one of the most common, life-threatening, gastrointestinal disorders in neonates. The recovery time for neonates with NEC varies depending on disease severity, prompt diagnosis, and effective treatment. Therefore, this study was intended to assess the time to recover from necrotizing enterocolitis and its' predictors among neonates admitted to Neonatal Intensive Care Unit in Bahir Dar City, Ethiopia. An institution-based retrospective follow-up study design was employed. A sample of 361 medical records of neonates with necrotizing enterocolitis was selected using systematic random sampling. Diagnosis of NEC in this study required clinical, laboratory and radiographic findings. The survival function was described using Kaplan Meier survival curve and log-rank test. Bivariate and multivariate Cox-proportional hazard (Cox-PH) regression models were used for analysis. The median recovery time from necrotizing enterocolitis for neonates in the neonatal intensive care unit was 12 days. The multivariable Cox-PH model showed that neonates classified as Stage III NEC (AHR: 0.42, 95% CI = 0.23-0.77) and those exposed to perinatal asphyxia (AHR: 0.51, 95% CI: 0.35-0.74) had a negative impact on NEC recovery time. However, neonates with a birth weight of 1500-2499gm (AHR: 1.65, 95% CI: 1.05-2.58) and a platelet count greater than 150,000 (AHR: 1.75, 95% CI: 1.24-2.48) had a positive effect on NEC recovery time. The recovery time for neonates in the neonatal intensive care unit with necrotizing enterocolitis was longer. Comorbidities and advanced stage of NEC were associated with prolonged recovery time from NEC. However, neonates with better platelet count and birth weight greater than 1500mg had shorter recovery time from NEC.

Clinical significance of transjugular liver biopsy in acute liver failure – a real-world analysis

BackgroundHistopathological characterization obtained by transjugular liver biopsy (TJLB) may theoretically contribute to clarification of the exact aetiology of acute liver failure (ALF). It's unclear whether the histopathological information from TJLB, due to the small specimen size, significantly contributes to diagnosing ALF causes, guiding therapy decisions, or predicting overall prognosis. This retrospective study aimed to analyse safety and clinical significance of TJLB in patients with ALF.MethodsThis retrospective, monocentric study investigated safety and efficacy of TJLB in patients with ALF over a ten-year period at a tertiary care transplant-center. The predictive value of various clinical and laboratory characteristics as well as histopathological findings obtained by TJLB on 28-day liver-transplant-free survival were evaluated by calculating uni- and multivariate Cox-proportional hazard regression models. Additional univariate logistic regression analyses were performed to explore the influence of degree of intrahepatic necrosis on the secondary endpoints intensive-care-unit (ICU) admission, need for endotracheal intubation, renal replacement therapy and high-urgency listing for LTX.ResultsA total of 43 patients with ALF receiving TJLB were included into the study. In most cases (n = 39/43 cases) TJLB confirmed the initially already clinically presumed ALF aetiology and the therapeutic approach was unchanged by additional histological examination in the majority of patients (36/43 cases). However, in patients with a high suspicion for aetiologies potentially treatable by medical immunosuppression (e.g. AIH, GvHD), TJLB significantly influenced further treatment planning and/or adjustment. While the degree of intrahepatic necrosis showed significance in the univariate analysis (p = 0.04), it did not demonstrate a significant predictive effect on liver transplant-free survival in the multivariate analysis (p = 0.1). Only consecutive ICU admission was more likely with higher extent of intrahepatic necrosis (Odds ratio (OR) 1.04 (95% CI 1–1.08), p = 0.046).ConclusionsPerformance of TJLB in ALF led to a change in suspected diagnosis and to a significant change in therapeutic measures only in those patients with a presumed high risk for aetiologies potentially responsive to immunosuppressive therapy. Clinical assessment alone was accurate enough, with additional histopathological examination adding no significant value, to predict overall prognosis of patients with ALF.

Clinical characteristics and prognosis of childhood acute lymphoblastic leukemia with CD123 expression

To investigate the expression of CD123 in children with acute lymphoblastic leukemia (ALL) and its effect on the clinical characteristics and prognosis of children with B-lineage acute lymphoblastic leukemia (B-ALL). A retrospective analysis was conducted on the clinical data of 251 children with ALL who were admitted to the Department of Hematology and Oncology, Children's Hospital of Kunming Medical University, from December 2019 to June 2022. According to the expression of CD123 at initial diagnosis, the children were divided into CD123+ group and CD123- group, and the two groups were compared in terms of clinical characteristics and treatment outcome. The factors influencing the prognosis were analyzed. Among the 251 children with ALL, there were 146 children (58.2%) in the CD123+ group. The B-ALL group had a significantly higher positive expression rate of CD123 than the acute T lymphocyte leukemia group (P<0.05). Compared with the CD123- group, the CD123+ group had significantly lower peripheral blood leukocyte count and percentage of juvenile cells and a significantly higher proportion of children with high hyperdiploid karyotype or an age of 1-10 years, with a relatively low proportion of children with E2A-PBX1 fusion gene (P<0.05). The multivariate Cox proportional-hazards regression model analysis showed that compared with the >10 years group, the 1-10 years group had a significantly higher overall survival rate (P<0.05), and compared with the high risk group, the moderate risk group had a significantly higher event-free survival rate in children with B-ALL (P<0.05). CD123 is widely expressed in children with B-ALL, and positive expression of CD123 might be an indicator for good prognosis in children with B-ALL, which is of great significance for evaluating the efficacy of remission induction therapy and survival prognosis of children with B-ALL.

Oxidative balance score as a useful predictive marker for new-onset type 2 diabetes mellitus in Korean adults aged 60 years or older: The Korean Genome and Epidemiologic Study–Health Examination (KoGES-HEXA) cohort

BackgroundThe oxidative balance score (OBS) is a comprehensive pro- and anti-oxidative marker for assessing the risk of various metabolic diseases and cancers. However, it is not well established whether OBS is related to type 2 diabetes mellitus (T2DM), particularly in elderly populations. Therefore, our objective was to investigate the longitudinal effect of OBS on T2DM in a large cohort of Korean adults aged 60 years and older. MethodsWe assessed the data for 3516 participants aged 60 years and older without diabetes mellitus from the Health Examinees cohort of the Korean Genome and Epidemiology Study. We classified the participants into three groups according to OBS tertiles. We prospectively assessed hazard ratios (HRs) with 95 % confidence intervals (CIs) for new-onset T2DM using multivariable Cox proportional-hazard regression models during the mean 3.5 years following the baseline survey. ResultsA total of 109 participants (3.1 %) developed T2DM during a mean follow-up of 3.5 years. The incidence rates per 1000 person-years were 11.73 for the lowest OBS tertile (T1), 8.19 for the second tertile (T2), and 6.23 for the highest tertile (T3). Adjusting for all confounding factors, compared with the referent T1, the HR (95 % CI) of new-onset T2DM was not significant in T2 (0.71 [0.47–1.07]) but was significant in T3 at (0.47 [0.30–0.75]) (p for trend = 0.002). ConclusionsThe study suggests that a OBS could serve as a valuable predictive marker for new-onset T2DM in older adults. Our study suggests that maintaining an appropriate body weight through healthy lifestyle modification has the potential to lower T2DM incidence in elderly. This implies that the OBS may be a useful tool for assessing the incidence of T2DM even in older individuals.

Abstract PO4-02-12: MDA iLobular Prognostic Tool: A Novel Approach for Risk Stratification in Invasive Lobular Carcinoma

Abstract Background: Invasive lobular carcinoma (ILC) is a distinct subtype of breast cancer that differs from the more common invasive ductal carcinoma (IDC) by its unique characteristics that influence prognosis. Recent studies have shown that ILC is associated with worse long-term outcomes compared to IDC. Risk stratification is essential in breast cancer for tailoring treatment plans to the individual patient’s needs, maximizing the chances of successful outcomes and minimizing unnecessary interventions. Although there are multiple tools available for breast cancer, there is currently not a risk stratification tool that is specific for ILC. The MDA iLobular prognostic tool is the first risk stratification tool that has been developed specifically for ILC patients. Methods: We retrospectively searched for patients treated at MD Anderson Cancer Center with a diagnosis of stage I-III ILC in our prospectively collected electronic database. The study focused on two primary endpoints: Overall Survival (OS) and Distant Recurrence Free Survival (DRFS). We utilized univariate and multivariate Cox Proportional Hazard (PH) regression models to assess the statistical significance of all variables. The univariate Cox analysis identified prognostic factors, which were further analyzed using backward and stepwise multivariate Cox proportional hazards regression analysis. This process helped identify statistically significant prognostic factors that were included in the final multivariate models. We estimated hazard ratios and 95% confidence intervals for each factor, considering a P-value of &amp;lt; 0.05 as statistically significant. To evaluate the performance of the fitted multivariate Cox PH regression models for OS and DRFS, we randomly divided two-thirds of the data points into a training dataset, while the remaining one-third constituted the test dataset. We assessed the discrimination capacity of each model using Harrell's C-index. Results: The study included a total of 4,216 female patients, with a median age of 56 years. The median pathological tumor size was 2 mm, and the median number of lymph nodes was one. Among these patients, 1,376 were pre-menopausal, while 2,837 were post-menopausal. The training cohort was a subset of 2,950 patients and the test cohort was a subset of 1,266 patients. After evaluating various prognostic models, we identified the model with the highest prognostic accuracy for OS and DRFS. This selected model demonstrated a Harrell's C-index of 0.704 for OS and 0.718 for DRFS on the training dataset and a Harrell's C-index of 0.702 for OS and 0.671 for DRFS on the test dataset. The model incorporated several covariates, including age at the time of diagnosis, number of lymph nodes, pathological tumor size (mm), ER status, tumor grade, ILC histology, and the presence or absence of concomitant LCIS (Table 1). Conclusion: In conclusion, the MDA iLobular prognostic tool represents a significant advancement as the first dedicated tool for risk stratifying ILC, providing valuable guidance for tailoring therapy to individual ILC patients based on their specific risk profiles. Table 1. Multivariate Cox proportional hazard model parameter estimates for OS and DRFS Citation Format: Jason Mouabbi, Sarah Pasyar, Roland Bassett, Akshara Singareeka Raghavendra, Amy Hassan, Rachel Layman, Debu Tripathy. MDA iLobular Prognostic Tool: A Novel Approach for Risk Stratification in Invasive Lobular Carcinoma [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO4-02-12.

Long-term survival in stroke patients: insights into triglyceride-glucose body mass index from ICU data

BackgroundThe Triglyceride Glucose-Body Mass Index (TyG-BMI) has been established as a robust indicator of insulin resistance (IR), reflecting metabolic health across various populations. In general, lower TyG-BMI values are often associated with better metabolic health outcomes and a reduced risk of adverse health events in non-critically ill populations. Previous studies have highlighted a significant negative association between TyG-BMI and all-cause mortality (ACM) among critically ill atrial fibrillation patients. Given the high prevalence and severe outcomes associated with stroke, understanding how TyG-BMI at the time of ICU admission correlates with ACM in critically ill stroke patients becomes imperative. This study aims to assess the correlation between TyG-BMI and ACM in this specific patient cohort, exploring how traditional associations between TyG-BMI and metabolic health may differ in the context of acute, life-threatening illness.MethodsPatient data were retrieved by accessing the Medical Information Mart for Intensive Care IV (MIMIC-IV 2.2) database, categorizing patients into three groups on the basis of TyG-BMI tertiles. The study evaluated both primary and secondary outcomes: the primary outcomes included the 90-day, 180-day, and 1-year ACM, while secondary outcomes encompassed ICU, in-hospital, and 30-day ACM. Our study employed the Kaplan–Meier (K–M) curve method for outcome comparison across the groups while utilizing multivariate Cox proportional-hazards regression models and restricted cubic splines (RCS) to explore TyG-BMI association with these outcomes. Additionally, interaction and subgroup analyses were performed, focusing on different mortality time points.ResultsAmong a cohort of 1707 individuals diagnosed with stroke, the average age was 68 years (interquartile range [IQR]: 58–78 years), with 946 (55.42%) of the participants being male. The analysis of K-M curves suggested that patients having a lower TyG-BMI level faced a heightened risk of long-term ACM, whereas the short-term ACM exhibited no statistically significant differences across the three TyG-BMI groups. Furthermore, Cox proportional-hazards regression analysis validated a statistically significant increased risk of long-term ACM among patients belonging to the lowest TyG-BMI tertile. Additionally, RCS analysis results demonstrated L-shaped correlations between the TyG-BMI index and both short- and long-term ACM. These findings underscore the TyG-BMI predictive value for long-term mortality in stroke patients, highlighting a nuanced relationship that varies over different time frames. The results revealed no interactions between TyG-BMI and the stratified variables, with the exception of age.ConclusionIn our study, lower TyG-BMI levels in critically ill stroke patients are significantly related to a higher risk of long-term ACM within the context of the United States. This finding suggests the potential of TyG-BMI as a marker for stratifying long-term risk in this patient population. However, it's crucial to note that this association was not observed for short-term ACM, indicating that the utility of TyG-BMI may be more pronounced in long-term outcome prediction. Additionally, our conclusion that TyG-BMI could serve as a reliable indicator for managing and stratifying stroke patients over the long term is preliminary. To confirm our findings and assess the universal applicability of TyG-BMI as a prognostic tool, it is crucial to conduct rigorously designed research across various populations.

Outcome of Darunavir-Cobicistat-Based Regimens in HIV-Infected People Who Have Experienced Virological Failure.

To evaluate the virological outcome of darunavir-cobicistat (DRVc)-based regimens in adults living with HIV who had experienced virological failure (VF) on any previous drug combination. This was a retrospective cohort study (CSLHIV Cohort) of adults living with HIV who started a DRVc-based regimen with HIV-RNA >50 copies/mL after VF on any previous drug combination. Data on demographics, antiretroviral treatment since HIV diagnosis, and immunological and metabolic parameters from baseline (start of DRVc) to 48 weeks were analyzed in order to assess the cumulative proportion of those who achieved virological success (VS), defined as at least one instance of HIV-RNA <50 copies/mL within 12 months from baseline. Follow-up lasted from the start of the DRVc-based regimen (baseline) to the first instance of HIV-RNA <50 copies/mL, last available visit, or lossto follow-up or death, whichever occurred first. Univariate and multivariate Cox proportional-hazard regression models were used to identify baseline factors associated with VS. A total of 176 individuals were included, and 120 (68.2%) achieved <50 HIV-RNA copies/mL within 12 months since baseline. On multivariate analysis, baseline HDL cholesterol was independently associated with the occurrence of VS (adjusted HR 1.021, 95% CI 1.004-1.038; p=0.014). Among the 120 subjects with VS, 27 (22.5%) had had VF during a median follow-up of 20.8 months since the first undetectable HIV-RNA. Resistance testing after VF was available in two cases, which harboured the HIV variant-bearing protease inhibitor-resistance mutations D30N, I50V, and N88D. During a median follow-up of 38.4 months, 65 of 176 (36.9%) individuals discontinued DRVc for any reason (37 of 120, 30.8%) and achieved VS vs. 28 of 56 (50%) without VS (p=0.019). Time to discontinuation was longer in people with VS (41.5 vs. 23.0 months, p=0.0007). No statistically significant changes were observed in immunological or lipid profiles during follow-up. Most individuals in this study achieved VS within 12 months from the beginning of a DRVc-based regimen; therefore, this treatment represent a viable option for people who have experienced VF on other regimens.

METS-IR and all-cause mortality in Korean over 60 years old: Korean genome and epidemiology study-health examinees (KoGES-HEXA) cohorts.

The metabolic score for insulin resistance index (METS-IR) is a novel non insulin-based marker that indicates the risk for metabolic syndrome and type 2 diabetes mellitus (T2DM). However, METS-IR has not been investigated in relation to all-cause mortality. We investigated the longitudinal effect of METS-IR on all-cause mortality in a significantly large cohort of Korean adults over 60 years old. Data were assessed from 30,164 Korean participants over 60 years of age from the Korean Genome and Epidemiology Study-Health Examinees (KoGES-HEXA) cohort data, linked with the death certificate database of the National Statistical Office. The participants were grouped into three according to METS-IR tertiles. We used multivariate Cox proportional-hazard regression models to prospectively assess hazard ratios (HRs) for all-cause mortality with 95% confidence intervals (CIs) over an 11-year postbaseline period. During the mean 11.7 years of follow-up, 2,821 individuals expired. The HRs of mortality for METS-IR tertiles were 1.16 (95% CI, 1.01-1.34) in T3 after adjustment for metabolic parameters, but the T2 did not show statistical significance towards increases for incident mortality respectively. In subgroup analysis depending on the cause of mortality, higher METS-IR was associated with cancer mortality (HR, 1.23, 95% CI, 1.01-1.51) but not with cardiovascular mortality (HR, 1.14, 95% CI, 0.83-1.57) after adjustment for the same confounding variables. The METS-IR may be a useful predictive marker for all-cause mortality and cancer mortality, but not for cardiovascular mortality in subjects over 60 years of age. This implies that early detection and intervention strategies for metabolic syndrome could potentially benefit this identified group.

Having Plans for the Future in Very Old People.

This study aimed to investigate the prevalence of having plans for the future among very old people and the factors associated with having such plans. A longitudinal population-based study with home visits for 85-, 90-, and ≥95-year-old participants in Sweden and Finland was used. Multivariate logistic regression and Cox proportional-hazards regression models with a maximum 5-year follow-up period were used. The prevalence of having plans for the future was 18.6% (174/936). More men than women and more people living in Sweden than in Finland had plans for the future. In multivariate models, having plans for the future was associated with speaking Swedish, being dentate, and living in the community in the total sample; speaking Swedish and being dentate among women; and speaking Swedish, having a lower Geriatric Depression Scale score, and urban residence among men. Having plans for the future was associated univariately, but not multivariately, with increased survival.

Serum Soluble Receptors for Advanced Glycation End-Products May Predict Mortality in Microscopic Polyangiitis and Granulomatosis with Polyangiitis.

This study aimed to investigate whether the serum extracellular newly identified receptor for advanced glycation end products binding protein (EN-RAGE) and the soluble form of RAGE (sRAGE) measured at diagnosis are associated with all-cause mortality in patients with microscopic polyangiitis (MPA) and granulomatosis with polyangiitis (GPA). Serum EN-RAGE and sRAGE were measured in 75 immunosuppressive drug-naïve MPA and GPA patients using an immunoassay, with their clinical and laboratory data reviewed. The optimal cut-off point of EN-RAGE and sRAGE was calculated by finding the threshold with the maximum sum of sensitivity and specificity. In addition, the least absolute shrinkage and selection operator regression was adopted to select variables included in the multivariable Cox proportional hazards (PH) regression model. The median age of the patients was 67.0 years, and 34% were male. Neither serum EN-RAGE nor sRAGE at diagnosis was correlated with the Birmingham Vasculitis Activity Score. Furthermore, no correlation was observed between serum EN-RAGE and sRAGE. Deceased patients had significantly lower serum EN-RAGE and higher serum sRAGE at diagnosis compared to surviving patients. Patients with serum EN-RAGE at diagnosis ≤84.37 ng/mL and serum sRAGE at diagnosis ≥1.82 ng/mL showed significantly lower survival probabilities compared to those without. In multivariable Cox PH regression model, only serum sRAGE at diagnosis ≥1.82 ng/mL, rather than serum EN-RAGE at diagnosis ≤84.37 ng/mL, was independently associated with all-cause mortality (hazard ratio 7.094). This study is the first to demonstrate that serum sRAGE at diagnosis may independently predict all-cause mortality during follow-up in patients with MPA and GPA.

The Impact of Delayed Radical Prostatectomy on Recurrence Outcomes After Initial Active Surveillance: Results from a Large Institutional Cohort

Background and objectiveActive surveillance (AS) of prostate cancer (PCa) involves regular monitoring for disease progression. The aim is to avoid unnecessary treatment while ensuring appropriate and timely treatment for those whose disease progresses. AS has emerged as the standard of care for low-grade (Gleason grade 1, GG 1) PCa. Opponents are concerned that initial undersampling and delay of definitive management for patients with GG 2 disease may lead to adverse outcomes. We sought to determine whether the timing for definitive management of GG 2 PCa, either upfront or after initial AS, affects recurrence outcomes after radical prostatectomy (RP). MethodsParticipants were diagnosed with cT1–2N0/xM0/x, prostate-specific antigen (PSA) <20 ng/ml, and GG 1–2 PCa between 2000 and 2020 and underwent immediate RP for GG 2 or AS followed by delayed RP on upgrading to GG 2. The outcome was recurrence-free survival (RFS) after surgery, with recurrence defined as either biochemical failure (2 PSA measurements ≥0.2 ng/ml) or a second treatment. Multivariable Cox proportional-hazards regression models were used to calculate associations between the timing for definitive RP and the risk of recurrence, adjusted for age at diagnosis, percentage of positive biopsy cores (PPC), PSA density, PSA before RP, year of diagnosis, surgical margins, genomic risk score, and prostate MRI findings. Key findingsOf the 1259 men who met the inclusion criteria, 979 underwent immediate RP after diagnosis of GG 2, 190 underwent RP within 12 mo of upgrading to GG 2 on AS, and 90 men underwent RP >12 mo after upgrading to GG 2. The 5-yr RFS rates were 81% for the immediate RP group, 80% for the delayed RP ≤12 mo, and 70% for the delayed RP >12 mo group (univariate log-rank p = 0.03). Cox multivariable regression demonstrated no difference in RFS outcomes between immediate RP for GG 2 disease and delayed RP after upgrading on AS. PPC (hazard ratio [HR] per 10% increment 1.08, 95% confidence interval [CI] 1.02–1.15; p = 0.01) and PSA before RP (HR 1.06, 95% CI 1.03–1.09; p < 0.01) were significantly associated with the risk of recurrence. Conclusions and clinical implicationsPPC and PSA before RP, but not the timing of definitive surgery after upgrade to GG 2, were associated with the risk of PCa recurrence after RP on multivariable analysis. These findings support the safety of AS and delayed definitive therapy for a subset of patients with GG 2 disease. Patient summaryIn a large group of 1259 patients with low-grade prostate cancer, we found that delaying surgical treatment after an initial period of active surveillance resulted in no differences in prostate cancer recurrence. Our results support the safety of active surveillance for low-grade prostate cancer.

Development of an online calculator for the prediction of seizure freedom following pediatric hemispherectomy using the Hemispherectomy Outcome Prediction Scale (HOPS).

Although hemispheric surgeries are among the most effective procedures for drug-resistant epilepsy (DRE) in the pediatric population, there is a large variability in seizure outcomes at the group level. A recently developed HOPS score provides individualized estimation of likelihood of seizure freedom to complement clinical judgement. The objective of this study was to develop a freely accessible online calculator that accurately predicts the probability of seizure freedom for any patient at 1-, 2-, and 5-years post-hemispherectomy. Retrospective data of all pediatric patients with DRE and seizure outcome data from the original Hemispherectomy Outcome Prediction Scale (HOPS) study were included. The primary outcome of interest was time-to-seizure recurrence. A multivariate Cox proportional-hazards regression model was developed to predict the likelihood of post-hemispheric surgery seizure freedom at three time points (1-, 2- and 5- years) based on a combination of variables identified by clinical judgment and inferential statistics predictive of the primary outcome. The final model from this study was encoded in a publicly accessible online calculator on the International Network for Epilepsy Surgery and Treatment (iNEST) website (https://hops-calculator.com/). The selected variables for inclusion in the final model included the five original HOPS variables (age at seizure onset, etiologic substrate, seizure semiology, prior non-hemispheric resective surgery, and contralateral fluorodeoxyglucose-positron emission tomography [FDG-PET] hypometabolism) and three additional variables (age at surgery, history of infantile spasms, and magnetic resonance imaging [MRI] lesion). Predictors of shorter time-to-seizure recurrence included younger age at seizure onset, prior resective surgery, generalized seizure semiology, FDG-PET hypometabolism contralateral to the side of surgery, contralateral MRI lesion, non-lesional MRI, non-stroke etiologies, and a history of infantile spasms. The area under the curve (AUC) of the final model was 73.0%. Online calculators are useful, cost-free tools that can assist physicians in risk estimation and inform joint decision-making processes with patients and families, potentially leading to greater satisfaction. Although the HOPS data was validated in the original analysis, the authors encourage external validation of this new calculator.

Mid-arm muscle circumference and triceps skinfold thickness associated with cardiometabolic disease in Chinese residents: A prospective cohort study

Background and aimsThe association of cardiometabolic disease (CMD) with body muscle and fat mass remains unclear. Mid-arm muscle circumference (MAMC) and triceps skinfold (TSF) thickness are easily obtained measuring methods for these two body compositions. This study aimed to investigate the association of CMD with MAMC and TSF thickness among Chinese residents. MethodsA total of 9440 eligible participants from the China Health and Nutrition Survey were included in the analysis. Associations of CMD prevalence with MAMC and TSF thickness were estimated using logistic regression models. Multivariable COX proportional-hazards regression models were used to estimate the effect of baseline MAMC and TSF thickness on subsequent CMD. ResultsPositive associations of CMD prevalence with MAMC (odds ratio [OR] = 1.169, 95% confidence interval [CI] 1.110-1.232, P < 0.001) and TSF thickness (OR = 1.313, 95%CI 1.240-1.390, P < 0.001) were observed in the cross-sectional analysis. In the longitudinal study, a 1-SD increase in MAMC was associated with a 13.6% increased risk of CMD incidence (hazard ratio [HR] = 1.136, 95%CI 1.073-1.204, P < 0.001), and a 1-SD increase in TSF thickness had a 17.6% increased risk of CMD incidence (HR = 1.176, 95%CI 1.084-1.276, P < 0.001). For the CMD components, both MAMC and TSF thickness contributed to increased incidences of hypertension (HR = 1.163, 95%CI 1.097-1.233, P < 0.001 in MAMC; HR = 1.218, 95%CI 1.110-1.336, P < 0.001 in TSF thickness) and diabetes mellitus (HR = 1.166, 95%CI 1.028-1.323, P = 0.017 in MAMC; HR = 1.352, 95%CI 1.098-1.664, P = 0.004 in TSF thickness). ConclusionsIndividuals with higher MAMC and TSF thickness had an increased incidence of CMD, mainly hypertension and diabetes mellitus. This study revealed a seemingly counterintuitive association between body muscle mass and metabolic homeostasis. Although the potential mechanisms require further exploration, the impact of body muscle mass on metabolic health cannot be ignored.

Sex-specific associations of γ-glutamyltransferase to HDL-cholesterol ratio and the incident risk of cardiovascular disease: three Korean longitudinal cohorts from different regions.

The combination of gamma-glutamyl transferase (GGT) and high-density lipoprotein cholesterol (HDL-C) (GGT/HDL-C) is a novel noninsulin-based marker for assessing the risk of nonalcoholic fatty liver disease and type 2 diabetes mellitus. However, whether the GGT/HDL-C ratio is related to the risk of incident cardiovascular disease (CVD) risk is not well known. Therefore, we aimed to investigate the longitudinal effect of GGT/HDL-C ratio on incident CVD risk in three large cohorts of Korean men and women. Data were assessed from 27,643 participants without CVD from the Korean Genome and Epidemiology Study (KoGES), Health Risk Assessment Study (HERAS), and Korea Health Insurance Review and Assessment (HIRA) (HERAS-HIRA) datasets. The participants were divided into four groups according to the GGT/HDL-C quartiles. We prospectively assessed hazard ratios (HRs) with 95% confidence intervals (CIs) for CVD using multivariate Cox proportional-hazard regression models over a 50-month period following the baseline survey. During the follow-up period, 949 patients (3.4%; 529 men and 420 women) developed CVD. The HRs of CVD for GGT/HDL-C quartiles 2-4 were 1.36 (95% CI, 0.91-2.02), 1.54 (95% CI, 1.05-2.26), and 1.66 (95% CI, 1.12-2.47) after adjusting for metabolic parameters in women, but GGT/HDL-C did not show a trend toward increases in incident CVD in men. Regional discrepancies were evident in the results; the increase in HR in the metropolitan hospital cohort was more pronounced than that in the urban cohort, and the risk was not increased in the rural cohort. GGT/HDL-C ratio may be a useful predictive marker for CVD in women. Furthermore, the prevalence of CVD was strongly correlated with the GGT/HDL-C ratio in metropolitan areas, and this correlation was more significant than that observed with GGT or HDL-C in isolation.

Prediction of Incident Depression in Middle-Aged and Older Adults using Digital Gait Biomarkers Extracted from Large-Scale Wrist Sensor Data.

To determine if digital gait biomarkers captured by a wrist-worn device can predict the incidence of depressive episodes in middle-age and older people. Longitudinal cohort study. A total of 72,359 participants recruited in the United Kingdom. Participants were assessed at baseline on gait quantity, speed, intensity, quality, walk length distribution, and walk-related arm movement proportions using wrist-worn accelerometers for up to 7days. Univariable and multivariable Cox proportional-hazard regression models were used to analyze the associations between these parameters and diagnosed incident depressive episodes for up to 9years. A total of 1332 participants (1.8%) had incident depressive episodes over a mean of 7.4 ± 1.1years. All gait variables, except some walk-related arm movement proportions, were significantly associated with the incidence of depressive episodes (P < .05). After adjusting for sociodemographic, lifestyle, and comorbidity covariates; daily running duration, steps per day, and step regularity were identified as independent and significant predictors (P < .001). These associations held consistent in subgroup analysis of older people and individuals with serious medical conditions. The study findings indicate digital gait quality and quantity biomarkers derived from wrist-worn sensors are important predictors of incident depression in middle-aged and older people. These gait biomarkers may facilitate screening programs for at-risk individuals and the early implementation of preventive measures.

The healthy beverage index is not associated with insulin resistance, prediabetes and type 2 diabetes risk in the Rotterdam Study.

Whether beverage quality affects changes in glycaemic traits and type 2 diabetes (T2D) risk is unknown. We examined associations of a previously developed Healthy Beverage Index (HBI) with insulin resistance, and risk of prediabetes and T2D. We included 6769 participants (59% female, 62.0 ± 7.8years) from the Rotterdam Study cohort free of diabetes at baseline. Diet was assessed using food-frequency questionnaires at baseline. The HBI included 10 components (energy from beverages, meeting fluid requirements, water, coffee and tea, low-fat milk, diet drinks, juices, alcohol, full-fat milk, and sugar-sweetened beverages), with a total score ranging from 0 to 100. A higher score represents a healthier beverage pattern. Data on study outcomes were available from 1993 to 2015. Multivariable linear mixed models and Cox proportional-hazards regression models were used to examine associations of the HBI (per 10 points increment) with two measurements of HOMA-IR (a proxy for insulin resistance), and risk of prediabetes and T2D. During follow-up, we documented 1139 prediabetes and 784 T2D cases. Mean ± SD of the HBI was 66.8 ± 14.4. Higher HBI score was not associated with HOMA-IR (β: 0.003; 95% CI -0.007, 0.014), or with risk of prediabetes (HR: 1.01; 95% CI 0.97, 1.06), or T2D (HR: 1.01; 95% CI 0.96, 1.07). Our findings suggest no major role for overall beverage intake quality assessed with the HBI in insulin resistance, prediabetes and T2D incidence. The HBI may not be an adequate tool to assess beverage intake quality in our population.

A mixed-method study examined the reasons why pregnant women late initiate antenatal care in Northeast Ethiopia.

Timely initiation of antenatal care visits is crucial for ensuring optimal care and health outcomes for women and children. However, late antenatal care initiation among pregnant women in low-income countries including Ethiopia is acknowledged in the literature. Therefore, this study examined why pregnant women initiate antenatal care late in Northeast Ethiopia. This study was done using a mixed design approach that included phenomenology and retrospective cross-sectional designs. A retrospective cross-sectional study was deployed among randomly selected 632 medical charts of women who had antenatal care visit in Legambo District primary hospital and health centers. Kaplan Meier curve was used to estimate survival time. Bi-variable and multivariable Cox-proportional hazard regression models were fitted using R-studio-1.2.5033 to identify independent predictors of antenatal care initiation time. Six vignette-based focused group discussions were held with pregnant women who had been purposefully selected. Then, a qualitative content analysis that was informed by the phenomenological theory was done. This study indicated that only 195 (30.9%) of women timely initiated their antenatal care follow-up. In a survival analysis, all 632 women contributed 12,474 person-weeks giving a timely antenatal care initiation rate of 15.6 per 1000 person-weeks. According to the multivariable Cox regression models, late antenatal are initiation was found among pregnant women with an unknown last normal menstruation period, no living children, no bad obstetric history, not accompanied by their partner during antenatal care visit, and who lived in a >5-kilometer radius of health facility. In a qualitative analysis, being uncertain whether the pregnancy had occurred, believing that they have a very low probability of experiencing any complications, negative experience with healthcare providers, negative influence from their immediate contacts such as the mother and mother-in-law, and socio-cultural beliefs like "Qare" were found as major reasons why they started antenatal care follow-up late. Most pregnant women in Legambo district, northeastern Ethiopia, initiate their antenatal care visits late. Based on the findings of this study, strengthening the pregnant women identification program and performing regular pregnant women's conference will help to achieve early initiation of antenatal care visits. To lessen the negative influence of their immediate contacts, it will also good to include these old moms and husbands in the conference of pregnant women.

Abstract LB119: Recurrence score for recurrence over survival outcome in the landmark TAILORx trial

Abstract Overall survival is the most relevant endpoint in clinical research and patient care. Nonetheless, cancer recurrence has been frequently utilized as a surrogate endpoint, particularly in the context of multi-gene assays and molecular signatures. The 21-gene recurrence score (RS) was originally established against distant recurrence for prognosis in breast cancer. However, it is unclear whether RS has a weight for the recurrence over survival prognosis. We investigated RS on the choice of clinical endpoints in the Trial Assigning Individualized Options for Treatment (TAILORx), which had OS, invasive disease-free survival (DFS), and recurrence-free interval (RFI) in addition to distant recurrence-free interval as the clinical endpoints. Both midrange (11-25) and high-range (26-100) scores were associated with RFI, high-range only with DFS, but not significantly associated with OS in the multivariable Cox proportional-hazards regression models. Of 462 death events, 33.1% (153 events) were ascribed to breast cancer and 91.8% (424) were due to DFS-related events that included 24.5% other cancers, 34.2% unknown and 33.1% breast cancer. It is DFS that was wound up as the most representative surrogate endpoint for survival. The lack of survival significance was probably due to the nature of 21-gene assay weighted for recurrence rather than not having enough event numbers in the TAILORx clinical trial. The data call for establishing biomarkers directly towards OS or DFS to increase survival with more precision. Citation Format: Sherry X. Yang, John Yu, Molin Wang. Recurrence score for recurrence over survival outcome in the landmark TAILORx trial [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 2 (Clinical Trials and Late-Breaking Research); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(8_Suppl):Abstract nr LB119.

Long-term outcome of chronic thromboembolic pulmonary hypertension using direct oral anticoagulants and warfarin: a Japanese prospective cohort study

BackgroundChronic thromboembolic pulmonary hypertension (CTEPH) requires lifelong anticoagulation. Long-term outcomes of CTEPH under current anticoagulants are unclear. ObjectivesThe CTEPH AC registry is a prospective, nationwide cohort study comparing the safety and effectiveness of direct oral anticoagulants (DOACs) and warfarin for CTEPH. Patients/MethodsPatients with CTEPH, both tre atment-naïve and on treatment, were eligible for the registry. Inclusion criteria were patients aged ≥20 years and those who were diagnosed with CTEPH according to standard guidelines. Exclusion criteria were not specified. The primary efficacy outcome was a composite morbidity, and mortality outcome comprised all-cause death, rescue reperfusion therapy, initiation of parenteral pulmonary vasodilators, and worsened 6-minute walk distance and WHO functional class. The safety outcome was clinically relevant bleeding, including major bleeding. ResultsNine hundred twenty-seven patients on oral anticoagulants at baseline were analyzed: 481 (52%) used DOACs and 446 (48%) used warfarin. The 1-, 2-, and 3-year rates of composite morbidity and mortality outcome were comparable between the DOAC and warfarin groups (2.6%, 3.1%, and 4.2% vs 3.0%, 4.8%, and 5.9%, respectively; P = .52). The 1-, 2-, and 3-year rates of clinically relevant bleeding were significantly lower in DOACs than in the warfarin group (0.8%, 2.4%, and 2.4% vs 2.5%, 4.8%, and 6.4%, respectively; P = 0.036). Multivariable Cox proportional-hazards regression models revealed lower risk of clinically relevant bleeding in the DOAC group than the warfarin group (hazard ratio: 0.35; 95% CI: 0.13-0.91; P = .032). ConclusionThis registry demonstrated that under current standard of care, morbidity and mortality events were effectively prevented regardless of anticoagulants, while the clinically relevant bleeding rate was lower when using DOACs compared with warfarin.

A Revised Version of the TNM Classification Leads to Optimized Predictive Performance in Patients with Adrenocortical Carcinoma.

The prognostic stratification of the current AJCC/UICC TNM classification for adrenocortical carcinoma (ACC) has been validated in only a few studies. In this study, it was hypothesized that redefining the T category cut-off would result in a significant improvement in estimated stage-related survival. In 935 patients with ACC from the SEER database, optimal cut-off values based on tumor size were first determined to redefine T1 and T2 categories. Cox proportional hazards regression analysis and receiver operating characteristics (ROC) were then used to determine the prognostic value of the revised version. A new cut-off value of 9.5 cm tumor size was established to differentiate between T1 and T2 tumors, leading to a revised TNM classification. As a result, a more homogeneous distribution of patients with ACC across all stages was observed. Notably, the predictive value of the newly proposed TNM classification in the ROC analysis exceeded that of the 7th and 8th editions of the AJCC/UICC classification system. Finally, the prognostic superiority of the revised TNM classification was confirmed in a multivariate Cox proportional hazards regression model. In conclusion, the present study demonstrates that updating the current staging system with revised T1 and T2 categories significantly improves the prediction of cancer-specific survival (CSS) in patients with ACC.