Multivariate Cox Proportional Hazards Model Research Articles

Dual-energy CT quantitative parameters for prediction of prognosis in patients with resectable rectal cancer.

To determine whether quantitative parameters derived from dual-energy CT (DECT) could predict prognosis in patients with resectable rectal cancer (RC). One hundred and thirty-four patients (recurrence/distant metastasis group, n = 36; non-metastasis/non-recurrence group, n = 98) with RC who underwent radical resection and DECT were retrospectively included. DECT quantitative parameters, including iodine concentration (IC), normalized iodine concentration (NIC), electron density (Rho), effective atomic number (Zeff), dual-energy index (DEI), the slope of the spectralHounsfield unit curve (λHU) on arterial and venous phase images. Univariate and multivariate Cox proportional hazards models were employed to identify independent risk factors of prognosis. The area under the receiver operating characteristic curve (AUC) was used to assess the performance. Disease-free survival (DFS) curves were constructed using the Kaplan-Meier method. Patients in the metastasis/recurrence group had higher Rho in arterial phase (A-Rho), NIC in venous phase (V-NIC), Rho in venous phase (V-Rho), Zeff in venous phase (V-Zeff), λHU in venous phase (V-λHU), pT stage, pN stage, serum carcinoembryonic antigen (CEA), carbohydrate antigen-199 levels and more frequent in extramural venous invasion than those in non-metastasis/non-recurrence group (all p < 0.05). V-NIC, V-λHU, and CEA were independent risk factors of recurrence/distant metastasis (all p < 0.05). The AUC of combined indicator integrating three independent risk factors achieved the best diagnostic performance (AUC = 0.900). In stratified survival analysis, patients with high V-NIC, V-λHU, and CEA had lower 3-year DFS than those with low V-NIC, V-λHU, and CEA. Combining V-NIC, V-λHU, and CEA could be used to noninvasively predict prognosis in resectable RC. Question TNM staging fails to accurately prognosticate; can quantitative parameters derived from dual-energy CT predict prognosis in patients with resectable rectal cancer? Findings Normalized iodine concentration (V-NIC) and the slope of the spectralHounsfield unit curve in venous phase (V-λHU), and carcinoembryonic antigen (CEA) are independent risk factors for recurrence/metastasis. Clinical relevance The combined indicator integrating V-NIC, V-λHU, and CEA could predict 3-year disease-free survival in patients with resectable rectal cancer and could aid in postoperative survival risk stratification to guide personalized treatment.

How long does it take to start minimal enteral feeding in preterm Neonates admitted to NICUs in Southern Oromia, Ethiopia?

BackgroundThe timely initiation of trophic feeding (TF) is crucial for premature newborns, but challenging due to immaturity, respiratory instability, abdominal distension, resource scarcity, and healthcare worker expertise. Moreover, there is a dearth of information on predictors of full trophic feeding time. Therefore, this retrospective cohort study aimed to investigate the time it takes and its predictors to initiate minimal enteral feeding in preterm neonates in Southern Oromia, Ethiopia.MethodA facility-based retrospective follow up study was conducted among 434 randomly selected preterm neonates admitted to NICU of Bule Hora University Teaching Hospital and Yabello General Hospital from January 1, 2021 to December 30, 2022. Data were extracted by a pretested structured checklist, entered into Epidata 3.1 and then transferred to Stata version 17 for analysis. Kaplan Meier survival curve and log rank test were used to estimate survival time and a statistical comparison respectively. Bivariable and multivariable cox proportional hazard model was fitted to identify predictors of time to initiate TF and their outputs are presented using Adjusted Hazard Ratio (AHR) with 95% Confidence Intervals (CIs).ResultThe overall incidence density of TF initiation was reported as 43.6 per 100 neonate-days. Moreover, the median (IQR) time to initiate TF was found to be 2 (1–4) days. Neonates delivered vaginally had a higher likelihood of early TF initiation (AHR: 1.64, CI: 1.26, 2.13), while those born between 32 and 34 weeks (AHR: 0.61, CI: 0.46, 0.81), VLBW neonates (AHR: 0.45, CI: 0.34, 0.60), neonates without KMC (AHR: 0.59, CI: 0.46, 0.79), and those in level II hospitals were less likely to start TF promptly (AHR: 0.78, CI: 0.62, 0.99). Furthermore, neonates with sepsis (AHR: 1.76, CI: 1.36, 2.28) and hypothermia (AHR: 1.51, CI: 1.19, 1.93) had delayed TF initiation.ConclusionWe observed a significant low rate of early TF initiation and higher death rate of preterm newborn in our study as compared to the global. Preterm neonates with lower GA, no KMC, and a VLBW are more likely to have a delayed initiation. Our results highlight that staff training on identifying neonates suitable for TF, and ensuring adequate resources for KMC in all NICU levels should be considered.

Prognostic Factors for Free Flap Failure in Head and Neck Reconstruction.

The failure rate of free flaps varies from 0.8% to 10.6% in the literature in head and neck reconstruction. The primary objective was to identify prognostic factors for free flap failure. We prospectively included all consecutive free flaps performed between August 2021 and January 2024, and used a multivariate Cox proportional hazard model. We included 307 free flaps, performed on 274 patients. Age, cardiovascular risk, radiotherapy history, type of flap, type of arterial anastomosis, and ischemia duration were not statistically linked to the risk of flap failure. In multivariate analysis, a venous anastomosis to the anterior jugular vein or to the superior thyroid vein were associated with an increased risk of flap failure, such as per- or postoperative revision of the anastomoses. The choice of venous anastomosis, appear to have a greater influence on the success or failure of a microvascularized transfer than patient characteristics.

Prenatal and Postnatal Nutritional Mismatch, Reflected by Birth Weight and Adult BMI, and Cardiometabolic Disease Risk.

This study aimed to investigate how nutritional exposures in early life, represented by birth weight (BW), and in later life, indicated by adult body mass index (BMI), interact to influence cardiometabolic disease (CMD) risk and to examine the underlying causal relationships. Included were 254,224 participants of White European ancestry from the UK Biobank. To evaluate the joint associations of BW and adult BMI with CMD risk, BW was categorized as low (LBW, <2.5 kg) or high (HBW, ≥2.5 kg), and BMI as low (LBMI, <30 kg/m²) or high (HBMI, ≥30 kg/m²). Multivariable Cox proportional hazards models and 2x2 factorial Mendelian randomization (MR) analyses were employed to assess these associations and the underlying causality. Compared to the participants with HBW-LBMI, the hazard ratio (HR) for atherosclerotic cardiovascular disease (ASCVD) was 1.19 (95% CI: 1.12 to 1.26) in the LBW-LBMI group, 1.33 (1.28 to 1.38) in the HBW-HBMI group, and 1.62 (1.50 to 1.75) in the LBW-HBMI group. The LBW-HBMI group also exhibited higher risks for hypertension (HR: 2.42 [2.26-2.59]), diabetes (HR: 5.16 [4.73-5.63]), and hyperlipidemia (HR: 1.95 [1.81-2.10]). Additive interactions between LBW and HBMI were identified for metabolic diseases but not for ASCVD. The causality of these associations was confirmed by MR analysis. Combined exposure to LBW and HBMI was most strongly associated with an elevated risk of CMD, underscoring the critical role of the mismatch between early-life and adult nutritional status in shaping long-term cardiometabolic health.

The association of triglyceride-glucose and triglyceride-glucose related indices with the risk of heart disease in a national

BackgroundThe association between triglyceride-glucose (TyG), triglyceride-glucose related indices and heart disease remains a topic of debate in the current literature. Existing evidence in Chinese people and in diabetes or non-diabetes patients regarding this association is limited, highlighting the need for further investigation.MethodsA cohort study was conducted involving 7945 participants enrolled in the China Health and Retirement Longitudinal Study (CHARLS). The incidence of heart disease was collected by following up 9 years. TyG, TyG with body mass index (BMI), waist circumference (WC), waist-to-height ratio (WHtR) were collected at baseline. Multivariate Cox proportional hazards models, restricted cubic spline (RCS), Kaplan-Meier (KM) curves, subgroup analysis and sensitivity analysis were used to analyze the associations between TyG, TyG related indices and the risk of heart disease in national participants and in type 2 diabetes (T2D) or non-T2D patients respectively.ResultsDuring a 9-year follow-up, 1477 participants (18.6%) developed heart disease. Our analysis found a significant positive association between TyG-BMI, TyG-WC, and TyG-WHtR with heart disease risk in all participants. The adjusted hazard ratios (HR) for the highest quartile compared to the lowest were: TyG-BMI 1.73 (95% CI: 1.47–2.03), TyG-WC 1.46 (95% CI: 1.24–1.71), and TyG-WHtR 1.31 (95% CI: 1.11–1.54). However, TyG alone was not significantly associated with heart disease in all participants. In non-diabetic patients, the associations were consistent: TyG-BMI 1.75 (95% CI: 1.47–2.08), TyG-WC 1.47 (95% CI: 1.24–1.75), and TyG-WHtR 1.34 (95% CI: 1.13–1.60). However, in diabetes patients, no significant associations were found between TyG, TyG-WC, TyG-WHtR and heart disease risk except for the highest quartile of TyG-BMI (HR: 1.86, 95% CI: 1.02–3.40).ConclusionsIn the national population study, higher TyG-BMI, TyG-WC, and TyG-WHtR indices were significantly associated with an increased risk of heart disease, with TyG-BMI and TyG-WC showing stronger correlations. While this association was evident in non-T2D patients, only TyG-BMI was associated with heart disease incidence in T2D patients, underscoring the necessity for further investigation.

Relationship between longitudinal changes in lipid composition and ischemic stroke among hypertensive patients.

Dyslipidemia was strongly linked to stroke, however the relationship between dyslipidemia and its components and ischemic stroke remained unexplained. To investigate the link between longitudinal changes in lipid profiles and dyslipidemia and ischemic stroke in a hypertensive population. Between 2013 and 2014, 6094 hypertension individuals were included in this, and ischemic stroke cases were documented to the end of 2018. Longitudinal changes of lipid were stratified into four groups: (1) Normal was transformed into normal group; (2) Abnormal was transformed into normal group; (3) Normal was transformed into abnormal group; and (4) Abnormal was transformed into abnormal group. To examine the link between longitudinal changes in dyslipidemia along with its components and the risk of ischemic stroke, we utilized multivariate Cox proportional hazards models with hazard ratio (HR) and 95%CI. The average age of the participants was 62.32 years ± 13.00 years, with 329 women making up 54.0% of the sample. Over the course of a mean follow-up of 4.8 years, 143 ischemic strokes happened. When normal was transformed into normal group was used as a reference, after full adjustments, the HR for dyslipidemia and ischemic stroke among abnormal was transformed into normal group, normal was transformed into abnormal group and abnormal was transformed into abnormal group were 1.089 (95%CI: 0.598-1.982; P = 0.779), 2.369 (95%CI: 1.424-3.941; P < 0.001) and 1.448 (95%CI: 1.002-2.298; P = 0.047) (P for trend was 0.233), respectively. In individuals with hypertension, longitudinal shifts from normal to abnormal in dyslipidemia-particularly in total and low-density lipoprotein cholesterol-were significantly associated with the risk of ischemic stroke.

Treatment practices and survival outcomes for IDH-wildtype glioblastoma patients according to MGMT promoter methylation status: insights from the U.S. National Cancer Database.

Methylation of the O6-methylguanine-DNA methyltransferase (MGMT) promoter is an important prognostic marker in glioblastoma (GBM); however, its implementation in clinical practice remains understudied. Here, we assessed the prevalence of MGMT methylation status among GBM patients in the United States. Additionally, we evaluated treatment practices and survival outcomes of GBM patients according to MGMT promoter methylation status. The National Cancer Database was queried to identify all adult U.S. patients (≥ 18 years) diagnosed with IDH-wildtype GBM between 2018 and 2020. Treatment regimen was grouped into no chemotherapy and no radiotherapy, chemotherapy alone (without radiotherapy), radiotherapy alone (without chemotherapy), and chemoradiotherapy (chemotherapy and radiotherapy). Survival data were analyzed using Kaplan-Meier survival curves, log-rank tests, and multivariable Cox proportional hazard modeling. A total of 20,734 patients were included, of whom 6,404 (30.9%) had MGMT-methylated GBM, 9,065 (43.7%) had MGMT-unmethylated tumors, and 5,265 (25.4%) had unknown methylation status. The median and three-year overall survival were 12.4 months and 15.5%, respectively, for the entire cohort (16.4 months and 23.9% for MGMT-methylated patients and 11.8 months and 9.8% for MGMT-unmethylated patients, p < 0.001). Chemoradiotherapy was less commonly used for elderly (≥ 70 years, 58.5%) than non-elderly (< 70 years, 79.2%) patients. Among elderly patients, radiotherapy alone was more commonly administered than chemotherapy alone for patients with MGMT-unmethylated tumors (11.2% vs. 2.1%) and MGMT-methylated tumors (6.6% vs. 3.9%). However, chemotherapy alone was associated with a lower mortality risk (HR 0.71, 95% CI 0.51-0.99, p = 0.04) than radiotherapy alone for elderly patients with MGMT-methylated tumors, while chemotherapy alone was associated with a higher mortality risk (HR 1.63, 95% CI 1.09-2.44, p = 0.02) than radiotherapy alone for elderly patients with MGMT-unmethylated tumors. Patients who were elderly, uninsured, insured through Medicaid, lived in zip codes with lower median education levels, or received care at non-academic programs were less likely to undergo MGMT testing. A high proportion of GBM patients in the United States undergo MGMT promoter testing, though significant sociodemographic disparities exist. While there was a decrease in chemoradiotherapy use with increasing age, radiotherapy alone was more commonly administered to elderly patients than chemotherapy alone irrespective of MGMT promoter methylation status.

A multicenter analysis to identify the risk factors for stroke recurrence and mortality within 1 year

BackgroundStroke recurrence is a serious and prevalent complication of ischemic stroke that warrants additional investigation.MethodsA hospital-based retrospective observational study included acute-subacute ischemic stroke adult patients. The primary aim was to determine the risk factors associated with recurrent stroke within 365 days. Additionally, a combined outcome consisting of any stroke recurrence or all-cause mortality within 365 days was considered secondary outcome. Univariate and multivariable Cox proportional-hazards models were used to examine the association of risk factors with stroke recurrence and composite death/stroke recurrence.ResultsOf 1,244 patients, 112 (9%) experienced stroke recurrence. The multivariable analysis identified risk factors for stroke recurrence including history of previous stroke (HR = 3.65, 95% CI:2.28–5.99, p = 0.0001), tissue plasminogen activator (tPA) treatment (HR = 2.84, 95% CI:1.57–4.86, p = 0.0003), seizure (HR = 1.96, 95% CI:1.14–3.22, p = 0.0105), and depression (HR = 2.26, 95% CI:1.33–3.69, p = 0.0016). Only previous stroke history (HR = 2.37, 95% CI:1.74–3.26, p = 0.0001) remained significantly associated with the combined outcome of stroke recurrence/death. Additional risk factors for the composite outcome included older age of patients (HR = 1.02, 95% CI:1.01–1.03, p = 0.0009), admission to the intensive care unit (ICU) (HR = 3.70, 95% CI:2.63–5.22, p = 0.0105), pneumonia (HR = 1.47, 95% CI:1.05–2.05, p = 0.0249), and brain edema (HR = 2.36, 95% CI:1.58–3.46, p = 0.0001).ConclusionKey findings include a stroke recurrence rate of 9.96% and a combined death/stroke recurrence rate of 21.83% within 365 days. Multivariable analysis confirmed that history of stroke, receiving tPA, experiencing seizures, and depression were significantly associated with stroke recurrence. Implementing additional preventive measures for individuals in these high-risk categories is essential. Further studies are needed to validate our findings.

Survival and risk factors for metastatic colorectal cancer patients with a history of prior malignancy

Given concerns about treatment, there is uncertainty surrounding the effect of prior malignancy on the survival of individuals with metastatic colorectal cancer. This study sought to evaluate how prior malignancy impacts the survival of patients with metastatic colorectal cancer (mCRC). Patients diagnosed with stage IV mCRC (per the American Joint Committee on Cancer [AJCC] 6th edition) between 2004 and 2015 were identified from the Surveillance, Epidemiology, and End Results (SEER) database. Those without a prior history of malignancy were assigned to the control group, whereas those with a prior history of malignancy were assigned to the research group. Propensity score matching (PSM) was utilized to ensure that the baseline characteristics were balanced. The Kaplan‒Meier method was used for survival analysis, as were the multivariate Cox proportional hazard model and multivariate competing risk model. The PSM analysis included 54365 eligible patients with mCRC. Among them, 4,845 (8.9%) had a history of prior malignancy. A history of prior malignancy was associated with a greater cancer-specific survival rate (adjusted hazard ratio (AHR) ) = 0.49; 95% CI [0.47–0.51]). Subgroup analyses revealed that a prior diagnosis of a skin tumour (AHR = 1.37; 95% CI [1.11–1.69]) and a history of prior malignancy of more than five years (AHR = 1.39; 95% CI [1.23–1.57]) had adverse effects on the clinical outcomes of patients with mCRC. Our findings suggest that patients with a prior malignancy diagnosis may experience prolonged survival. Subgroup analysis indicated that a malignancy diagnosed more than 5 years ago may adversely impact the clinical outcomes of patients with mCRC. Therefore, we advocate for active standardized treatment for these patients and propose expanding the range of prior malignancies included in clinical trials based on publication timelines, primary tumour locations, and genetic testing results. The objective is to facilitate timely and proactive treatment for patients following the disclosure of results, thereby instilling confidence in the management of mCRC.

Abstract 18: Relation of Migraine to Stroke Risk in Postmenopausal Women: Findings from the Women’s Health Initiative

Introduction: Migraines are a known risk factor for stroke among reproductive-aged women, though the relation of migraines to stroke risk among postmenopausal women remains unclear. We assessed the association between a history of diagnosed migraine and incident stroke among postmenopausal women and investigated age differences in the association. Methods: We included women enrolled in the Women’s Health Initiative (WHI), a large longitudinal cohort study of postmenopausal women in the U.S. We excluded women with a history of stroke or TIA at baseline or with missing data on history of migraine or key covariates. The primary exposure was a history at baseline of self-reported migraine diagnosed by a physician. The primary outcome was incident stroke (total, ischemic [IS], or hemorrhagic [ICH]). Multivariable Cox proportional hazards models were used to test the cause-specific hazard ratios (HRs) between migraine history and total stroke, IS (overall and by subtype), and ICH, sequentially adjusted for age and traditional and female-specific risk factors. Using multivariable Cox proportional hazard models, we then quantified the association between migraine history and total stroke by age in 5-year groups at baseline. Results: 130,277 participants were included. The median age at baseline was 61 years (IQR 56-67 years) for those with a migraine history compared to 63 years (IQR 57-69 years) for those without. Overall, 5,743 strokes occurred over a median follow-up period of 19.9 years (IQR 9.1-25). In multivariable-adjusted models (Table), there was a marginal association between migraine history and total stroke (HR=1.07; 95% CI, 0.99-1.17) and a significant association between migraine history and IS (HR=1.12; 95% CI, 1.02-1.23), most pronounced in the cardioembolic category. Migraine was not associated with risk of ICH (HR=0.85, 95%CI, 0.67-1.09). Risk appears to be of greatest magnitude in early (HR 1.26, 95% 0.93-1.72) and late (HR 1.16, 95%CI 0.89-1.50) postmenopausal years (Figure), though the differences by age group were not statistically significant. Conclusions: Over a 20-year follow-up period, postmenopausal women with self-reported histories of migraine had a higher risk of IS, but not total or ICH, suggesting that migraine history contributes to ischemic stroke risk during the postmenopausal years. Along with other known risk factors, migraine history should be considered in stroke risk factor screening and prevention efforts after menopause.

Changes in peri-operative chemotherapy and radiation use among patients with resected pancreatic ductal adenocarcinoma (PDAC) between 2004-2021 in the US SEER dataset.

697 Background: PDAC peri-operative management changed over 20 years. Randomized data supports adjuvant and multiagent chemotherapy (CT), while peri-operative chemoradiotherapy (RT) was used selectively in the US. We examined recent trends in treatment with outcomes in surgically resected PDAC patients. Methods: Using the Surveillance, Epidemiology, and End Results (SEER) 17 dataset, we identified surgically resected primary M0/MX PDAC cases from 2004-2021 over 3-year periods (P1-P6). Neoadjuvant (NCT), adjuvant (ACT), or multiagent (MACT) CT scheduling was included. χ² analysis assessed cohort characteristics over time and multinomial logistic regression assessed odds of CT allocation adjusted by cohort characteristics. Multivariable Cox proportional hazards model assessed treatment-related overall survival (OS) adjusted for cohort characteristics. Results: Among 55,293 cases of M0/MX PDAC, 21,904 (40%) completed surgery. Median age was 66 years; stages were T1/T2/T3/T4 (8.0/25/59/6.0%) and N0/N+ (38/54%). RT use declined (P1:P6, 41%-&gt;18% p&lt;0.001) while CT use increased (P2:P6, 63%-&gt;79%, p&lt;0.001). NACT (P2:P6, 4.1%-&gt;23% p&lt;0.001) and MACT (P2:P6, 1.6%-&gt;20%, p&lt;0.001) use increased while ACT decreased (P2:P6, 58%-&gt;36%, p&lt;0.001). CT is likely to be allocated to young patients (&lt;65yo) with Stage II-III tumors located at the pancreatic head (OR&gt;1.00, p&lt;0.001). Median OS increased over time (P1:P6, 18mo-&gt;32mo, p&lt;0.001). Multivariable analysis shows that Adjuvant RT (HR 0.84 [0.81-0.87], p&lt;0.001) and all CT (NCT: HR 0.71 [0.66-0.77], p&lt;0.001; ACT: HR 0.63 [0.60-0.66], p&lt;0.001; MACT: HR 0.65 [0.60-0.71], p&lt;0.001) improved OS. Conclusions: This study shows decreased RT and increased CT adoption from 2004-2021. Median OS improved over the years, potentially due to peri-operative advances during this study period. Trends in treatment use over 3-year periods. RTN (%) CTN (%) Neo CTN (%) MACTN(%) P1: 2004-2006N=2661 1087 (41) 0 (0) a 0 (0) a 0 (0) a P2: 2007-2009N=3185 1185 (37) 2021 (63) 129 (4.1) 50 (1.6) P3: 2010-2012N=3536 1226 (35) 2460 (70) 267 (7.6) 138 (3.9) P4: 2013-2015N=3947 1210 (31) 2880 (73) 434 (11) 244 (6.2) P5: 2016-2018N=4224 971 (23) 3256 (77) 676 (16) 491 (12) P6: 2019-2021N=4351 787 (18) 3430 (79) 1003 (23) 857 (20) a No cohorts reported chemotherapy use during period 1. RT: Radiation Therapy; CT: Chemotherapy; NCT: Neoadjuvant Chemotherapy; MACT: Multiagent Chemotherapy.

Clinical treatment score Post-5 Years (CTS5) predicts the benefit of postmastectomy radiotherapy in patients with T1-2N1 luminal breast cancer.

To investigate the clinical value of Clinical Treatment Score Post-5 Years (CTS5) to predict the survival benefits of postmastectomy radiotherapy (PMRT) of patients with T1-2N1 luminal breast cancer (BC). Patients who were diagnosed with T1-2N1 luminal BC between 2010 and 2015 were included in the Surveillance, Epidemiology, and End Results database. The chi-square test, binomial logistic regression, Kaplan-Meier analysis, and multivariable Cox proportional hazard model were used for statistical analyses. A total of 11190 patients were included with a median follow-up time of 76 months. Regarding the CTS5 classification, 1641 (14.7%), 3915 (35.0%), and 5633 (50.3%) patients had low-risk, intermediate-risk, and high-risk diseases, respectively. Patients with younger age, T2 stage, higher tumor grade, a higher number of positive lymph nodes, infiltrating lobular carcinoma subtype, and receipt of chemotherapy were associated with the receipt of PMRT (all P<0.05). The multivariate analysis showed that the receipt of PMRT was the independent prognostic factor associated with better BCSS (P=0.005) and OS (P<0.001). The sensitivity analysis showed that PMRT did not improve BCSS (low-risk, P=0.932; intermediate-risk, P=0.952) and OS (low-risk, P=0.637; intermediate-risk, P=0.825) compared to those without PMRT in the low-risk and intermediate-risk groups. However, PMRT improved BCSS (P=0.003) and OS (P<0.001) in those with high-risk groups compared to those without PMRT. CTS5 is an innovative model that could predict the survival benefit of PMRT for T1-2N1 luminal BC patients.

Kidney Biopsy-Proven Diabetic and Non-Diabetic Kidney Diseases and Outcomes in Patients With Type 2 Diabetes Receiving Dialysis: The REIN Registry.

Chronic kidney disease (CKD) in patients with diabetes does not always equate to diabetic kidney disease (DKD). This study aims to delineate and compare the clinical characteristics, survival rates, and access to kidney transplantation among patients with type 2 diabetes commencing dialysis, who were classified by kidney biopsy as having either DKD or non-diabetic kidney disease (non-DKD). We used the comprehensive French Renal Epidemiology and Information Network registry to analyze baseline clinical characteristics at dialysis inception and outcomes defined as death and access to kidney transplantation. We employed a multivariate Cox proportional hazards model and the Fine-Gray competing risk model to assess the probabilities of mortality and transplantation. Adults in the Renal Epidemiology and Information Network registry in France with a diagnosis of type 2 diabetes who initiated kidney replacement therapy from January 2009 to December 2015 and had a previous native kidney biopsy. We analyzed data from 2,869 patients with diabetes, 45% of whom had a biopsy-confirmed diagnosis of DKD. Among these patients, half presented additional histopathological findings indicative of nephroangiosclerosis and focal segmental glomerulosclerosis. The clinical profiles of patients with DKD and non-DKD were largely comparable. There were no significant differences in dialysis survival rates or kidney transplantation access between the groups, even after adjusting for confounding variables and considering competing risks. At the 6-year mark, the mortality rate was 60.3% (95% CI: 55.5-64.5) for the DKD group and 60.3% (95%CI: 55.9-64.3) for the non-DKD group. Multivariable Cox analysis revealed no significant difference in mortality risk between the DKD and non-DKD groups. The study limitations include potential residual confounders, lack of predialysis data, kidney biopsies possibly outdated, nonrandom biopsy indications, and survival bias because of analysis at dialysis inception. In patients with diabetes initiating dialysis, clinical characteristics and outcomes following dialysis initiation were similar in biopsy-proven DKD versus non-DKD. Our results suggest that the diabetic milieu has a more significant impact on outcomes in patients with diabetes treated with dialysis than the underlying pathological kidney diagnosis.

Survival in patients with rheumatoid arthritis and recently diagnosed early-stage colorectal, lung, or prostate cancer receiving tumour necrosis factor inhibitors: a retrospective cohort study.

Tumor necrosis factor (TNF) inhibitors could impair tumoural immunity in patients with rheumatoid arthritis and cancer. We aimed to investigate the association between survival and TNF inhibitor treatment during the first 3 years after a diagnosis of colorectal, lung, or prostate cancer in patients with rheumatoid arthritis. In this cohort study, we conducted a secondary data analysis of the Surveillance, Epidemiology, and End Results Medicare-linked dataset. We included patients aged 66 years and older with rheumatoid arthritis diagnosed with colorectal, lung, or prostate cancer between Jan 1, 2008, and Dec 31, 2019, using ICD-O-3 site and histology codes. We limited the cohort to patients who had early-stage cancer (localised or regional). We only included patients who received TNF inhibitors, conventional synthetic disease-modifying antirheumatic drugs (DMARDs), or no DMARDs in the first year after cancer diagnosis. The primary outcomes were 5-year overall survival and cancer-specific survival. Exposures were use of TNF inhibitors, conventional synthetic DMARDs, or no DMARDs within 3 years after cancer diagnosis. Other covariates included demographics and comorbidities. We conducted landmark analyses at years 1, 2, and 3, with Cox regression adjusted by propensity scores. People with lived experience of rheumatoid arthritis and cancer were not involved in the design or conduct of this study. We identified three cohorts of patients diagnosed with early-stage colorectal cancer (n=514), lung cancer (n=864), or prostate cancer (n=603) between Jan 1, 2008, and Dec 31, 2019. In the colorectal cancer cohort, the mean age was 76·1 years (SD 6·4), 385 (75%) of 514 patients were female, 129 (25%) were male, and 405 (79%) were White and non-Hispanic. In the lung cancer cohort, the mean age was 74·8 years (SD 5·9), 632 (73%) of 864 patients were female, 232 (27%) were male, and 743 (86%) were White and non-Hispanic. In the prostate cancer cohort, the mean age was 73·1 years (SD 5·1), 603 (100%) patients were male, and 492 (82%) were White and non-Hispanic. 80 (16%) of 514 patients with colorectal cancer, 102 (12%) of 864 patients with lung cancer, and 120 (20%) of 603 patients with prostate cancer received TNF inhibitors with or without conventional synthetic DMARDs at any time during the first year after cancer diagnosis. No significant deleterious association was observed for overall survival or cancer-specific survival for any of the cancers at any of the three landmark points. Hazard ratios and 95% CIs for overall survival for year 1 comparing TNF inhibitors with conventional synthetic DMARDs in the three cohorts were 0·72 (0·43-1·21) for colorectal cancer, 0·70 (0·49-1·00) for lung cancer, and 0·80 (0·44-1·44) for prostate cancer. Patients who received glucocorticoids in the first year had significantly worse overall survival and cancer-specific survival than those who did not in the multivariable Cox proportional hazards models for the three cancers. Treatment with TNF inhibitors during the first 3 years after diagnosis of colorectal, lung, or prostate cancer was not associated with poorer survival compared with those who received conventional synthetic DMARDs or those who did not receive any DMARDs. However, these findings might not be generalisable to other populations or types of cancer. National Institutes of Health (NIH)/National Institute of Arthritis and Musculoskeletal and Skin Diseases and NIH/National Cancer Institute through MD Andeson's Cancer Center Support Grant and Komen.

Association of malnutrition at diagnosis with survival among older adults with pancreatic cancer.

680 Background: Malnutrition is common among older adults newly diagnosed with pancreatic cancer. However, the implications of malnutrition among this vulnerable population are poorly understood. We sought to understand the association between malnourishment at diagnosis and overall survival (OS) among older adults with pancreatic cancer. Methods: We included adults aged ≥ 60 years with newly diagnosed pancreatic cancer, who were enrolled in the University of Alabama at Birmingham (UAB) Cancer and Aging Resilience Evaluation (CARE) registry between October 2017 and April 2024. To assess nutritional status, we administered an abridged version of the Patient-Generated Subjective Global Assessment (abPG-SGA) to patients at baseline prior to receiving chemotherapy. Using abPGSGA scores, we categorized patients as either normal (score ≤ 5) or malnourished (score ≥ 6). All participants were followed until death or until the cutoff date of July 10, 2024. We employed Kaplan-Meier survival analysis to estimate overall survival (OS) for both malnourished and non-malnourished groups and compared them using log-rank test. Additionally, we built multivariable Cox proportional hazards models to test the association between malnutrition and OS, while controlling for age at diagnosis, sex, race/ethnicity, and cancer stage. Results: A total of 274 patients were included; the median age at diagnosis was 70 (interquartile range, IQR: 65-75) years with 52% males, 75% non-Hispanic White and 52% with Stage IV disease at diagnosis. At baseline, 59% of patients were malnourished, and the median abPGSGA score was 8 (IQR 4-14). Patients who were malnourished had a similar demographic and clinical characteristics as compared to those without malnutrition. Over a median follow up of 36 months, a total of 202 patients (74 %) died. The median overall survival (OS) was significantly lower for malnourished patients at 13 months compared to 21 months for non-malnourished patients (log-rank test, p &lt; .001). After adjusting for potential age, sex, race/ethnicity and cancer stage, malnutrition at diagnosis remained independently associated with worse survival outcomes (adjusted HR: 1.762; 95% CI: 1.316–2.358; p &lt; .001). Conclusions: Our study reports that malnutrition at baseline is significantly associated with worse overall survival in older adults with pancreatic cancer. These findings underscore the importance of early nutritional assessment and intervention to enhance outcomes in this population.

An exploratory study of serum creatine kinase as a prognostic marker for patients with resectable pancreatic cancer: looking into the relationship with body composition

BackgroundAmong cancer patients, pancreatic cancer patients have the highest rate of sarcopenia, which is a critical prognostic factor. Serum creatine kinase (CK) is closely related to skeletal muscle mass and has been reported to decline with the progression of cancer. This study investigated whether preoperative serum CK is associated with the survival of patients with pancreatic cancer.MethodsData were obtained from patients with pathologically confirmed pancreatic cancer between June 2016 and March 2022. The prognostic significance of CK was analyzed based on sex-stratified groups. The Kaplan-Meier method was used to compare overall survival (OS) and disease-free survival (DFS). Multivariate Cox proportional hazards models were used to determine prognostic factors. Body composition was analyzed based on preoperative abdominal CT images to explore the sex-specific associations between skeletal muscle area (SMA) and serum CK levels.ResultsA total of 166 patients were included in this study. Sarcopenia was presented in 70 patients (42.2%). A low serum CK level showed a significant correlation with the diagnosis of sarcopenia in male patients (P = 0.026). The levels of CK did not predict the outcome in female patients, while a low preoperative CK was notably linked to shorter OS in male patients (median OS: 15 months vs. 33 months, P = 0.011; median DFS: 5 months vs. 14 months, P = 0.007). Multivariate analyses further confirmed the effect of CK in predicting OS (CK>44 IU/L, HR:0.226, 95% CI:0.107–0.478, P < 0.001) and DFS (CK>44 IU/L, HR:0.272, 95% CI:0.139–0.529, P < 0.001) of male patients. Correlation analysis revealed a significant association between SMA and CK levels in male patients (r = 0.225, P = 0.025), and such a correlation was not observed in female patients (r = 0.088, P = 0.478).ConclusionThe pretherapeutic CK may represent a simple marker for predicting poor survival in male patients with resectable pancreatic cancer, thereby aiding in the selection of therapeutic strategies.

Abdominal myosteatosis measured with computed tomography predicts poor outcomes in patients with glioblastoma.

Alterations in cellular metabolism affect cancer survival and can manifest in metrics of body composition. We investigated the effects of various body composition metrics on survival in patients with glioblastoma (GBM). We retrospectively analyzed patients who had an abdominal and pelvic computed tomography (CT) scan performed within 1 month of diagnosis of GBM (178 participants, 102 males, 76 females, median age: 62.1 years). Volumetric body composition metrics were derived using automated CT segmentation of adipose tissue, skeletal muscle, and aortic calcification from L1 to L5. Univariable and multivariable Cox proportional hazards models were performed separately in males and females using known predictors of GBM overall survival (OS) as covariates. A sex-specific composite score of predisposing and protective factors was constructed using the relative importance of each metric in GBM OS. Higher skeletal muscle volume and lower skeletal muscle fat fraction were associated with better OS in the entire dataset. A robust and independent effect on GBM OS was seen specifically for fraction of inter/intramuscular adipose tissue to total adipose tissue after correction for known survival predictors and comorbidities. Worse OS was observed with increased abdominal aortic calcification volume in both sexes. There was a significant difference in GBM OS among participants stratified into quartiles based on sex-specific composite predisposing and protective scores. The relationship between body composition and GBM OS provides an actionable advancement toward precision medicine in GBM management, as lifestyle and dietary regimens can alter body composition and metabolism and from there GBM survival.

Pulmonary rehabilitation and functional independence: Impact on survival in patients with fibrotic interstitial lung disease or chronic obstructive pulmonary disease.

Pulmonary rehabilitation (PR) aims to improve patients' functioning in interstitial lung disease (ILD) and chronic obstructive pulmonary disease (COPD). The impact of change in functional independence during PR on subsequent survival has not been established. We aimed to determine functional independence during PR and its association with survival over three years post-PR. This retrospective cohort study included patients with fibrotic ILD or COPD who participated in a 3-week inpatient PR program. The Functional Independence Measure (FIM) was assessed at PR entry and discharge. Correlations between FIM and demographics, clinical/functional parameters were analyzed. Time from PR to death/lung transplantation/censoring was assessed, stratified by baseline/changes in FIM above/below the median. Multivariable Cox proportional hazard models were used to determine the impact of FIM on mortality risk. 223 patients (76 ILD/147 COPD) were included. Mean±standard deviation (SD) age was 69±10 for ILD and 67±10 for COPD. FIM total and motor scores improved significantly in both groups. Baseline FIM showed a strong negative and change in 6-min walk distance (6MWD) a strong positive correlation with change in FIM during PR. Each 1-point increase in FIM motor score was associated with a 3% lower risk of mortality (HR 0.97, 95%CI 0.94-1, p=0.03). Inpatient PR improves functional independence in patients with fibrotic ILD or COPD, and baseline and change in FIM are associated with survival up to three years post-PR. This emphasizes the importance of PR for all patients with chronic lung disease regardless of their initial level of independence.

ASA Class Is a Stronger Predictor of Early Revision Risk Following Primary Total Knee Arthroplasty than BMI.

Although there is a known correlation between obesity and revision risk following total knee arthroplasty (TKA), there is an ongoing debate regarding the appropriateness of denying TKA solely based on the body mass index (BMI) of a patient. Our aim was to determine whether a patient's American Society of Anesthesiologists (ASA) class predicts their risks of early all-cause revision and revision for periprosthetic joint infection (PJI) following primary TKA, independent of their BMI. Data from the Australian Orthopaedic Association National Joint Replacement Registry (AOANJRR) were obtained regarding all patients who underwent primary TKA for osteoarthritis in Australia from January 1, 2015, to December 31, 2022. Estimated hazard ratios of all-cause revision and revision for PJI, as well as predicted risks of revision within 3 months, 1 year, and 2 years, as a function of patient ASA class and BMI, were calculated with use of multivariable Cox proportional hazards models. A total of 274,786 primary TKAs (54.5% female; mean age, 68.3 years) were included in the study, of which 5,401 were revised during the study period. Compared with BMI, ASA class was a stronger predictor of the risks of all-cause revision and revision for PJI following primary TKA. Patients with an ASA class of 3 to 4 had higher risks of all-cause revision and revision for PJI at multiple time points after TKA compared with patients with an ASA class of 1 to 2, regardless of BMI. Although ASA class and BMI are theoretically interrelated variables, we found that a patient's ASA class was more strongly associated with their risks of early all-cause revision and revision for PJI following primary TKA than their BMI. Employing a BMI threshold in isolation when assessing fitness for TKA may be inappropriate, and surgeons should give greater weight to the other medical comorbidities and general perioperative fitness of the patient. Patients with poorly controlled comorbidities should be referred for medical optimization prior to TKA. Prognostic Level III. See Instructions for Authors for a complete description of levels of evidence.

Impact of expression of metabolic genes on patient (pts) outcomes in metastatic colorectal cancer (mCRC): Data from CALGB/SWOG 80405 (Alliance).

224 Background: Metabolic pathways are reprogrammed during CRC development, leading to increased glycolysis, glutaminolysis, and fatty acid synthesis. Understanding the impact of metabolic reprogramming on treatment outcomes is paramount. Hence, we investigated whether the tumor gene expression of 4 selected major metabolic genes ( PKM, SLC2A1 , SLC16A1 , and CAV1 ) could affect treatment response in pts enrolled in the CALGB/SWOG 80405 trial. Methods: 433 mCRC pts treated with either bevacizumab (bev, n = 226) or cetuximab (cet, n = 207) in combination with first-line chemotherapy were analyzed. RNA was isolated from FFPE tumor samples and sequenced on the HiSeq 2500 (Illumina). Overall survival (OS) and progression-free survival (PFS) were compared between groups of pts categorized by tertiles of gene expression (high [H], medium [M] and low [L]). Logrank P -values provide a non-parametric unadjusted assessment of differences. Likelihood ratio tests (LRT) were computed from multivariate Cox proportional hazards models, adjusting for age, sex, ECOG, tumor side, number of metastatic sites, KRAS , CMS, and treatment. Results: PKM gene expression was associated with cet treatment outcomes with PKM- low tumors showing significantly longer PFS and OS (median PFS: 14.3 vs 9.8 vs 8.1 months, L vs M vs H, P &lt; 0.0001, LRT P = 0.011; median OS: 45.9 vs 31.2 vs 20.9 months, P &lt; 0.0001, LRT P = 0.12). Low SLC2A1 was also associated with longer OS in cet-treated pts (32.4 vs 35.8 vs 25.2 months, P = 0.02, LRT P &lt; 0.0001). Similar results were observed in bev-treated pts where low SLC2A1 expressing tumors had longer OS (37.4 vs 26.1 vs 29 months, P = 0.037, LRT P = 0.069) and a non-significant trend for longer PFS (13.1 vs 11 vs 9.5 months, P = 0.076). CAV1 low gene expression was associated with longer OS in cet-treated pts (37.4 vs 34 vs 21.5 months, P = 0.0048, LRT P = 0.013), while no significant associations were found in bev-treated (interaction LRT P = 0.0009). No significant results were observed for SLC16A1 . Conclusions: The intratumoral expression of metabolic genes was prognostic and predictive in mCRC pts treated with first-line therapy. GLUT1 (encoded by SLC2A1 ) and PKM2 (encoded by PKM ) promote aerobic glycolysis of cancer cells, known as Warburg effect, supporting rapid cell proliferation and survival. CAV1 has been shown to be involved in mitochondrial bioenergetics and fatty acid metabolism and to play either a tumor suppressor or oncogenic role depending on the cancer type and stage. Lower expression of SLC2A1 and PKM was associated with improved survival and increased benefit from cet treatment in our cohort. Low CAV1 expression was also associated with increase survival suggesting a cancer-promoting role in mCRC. Our results suggest that targeting cancer cell metabolism through novel inhibitors of the aforementioned pathways may be a promising therapeutic strategy.