Multivariate Cox Regression Model Research Articles

Association of glucagon-like peptide-1 receptor agonists with suicidal ideation and self-injury in individuals with diabetes and obesity: a propensity-weighted, population-based cohort study.

Regulators worldwide are reviewing safety data on glucagon-like peptide-1 receptor agonists (GLP-1RA), following reports by the Icelandic Medicines Agency in July 2023 of suicidal ideation and self-injury (SIS) in individuals taking liraglutide and semaglutide. We aimed to assess the risk of SIS in new users of GLP-1RA when compared with sodium-glucose cotransporter 2 inhibitors (SGLT-2i) users, prescribed to treat type 2 diabetes in individuals with obesity. This is a cohort study combining several population-wide databases and covering a Spanish population of five million inhabitants, including all adults with obesity who initiated treatment with either GLP-1RA or SGLT-2i for type 2 diabetes from 2015 to 2021. To estimate the comparative effect of GLP-1RA on the risk of SIS, we employed a new user, active comparator design and we carried out multivariable Cox regression modelling with inverse probability of treatment weighting (IPTW) based on propensity scores. We performed several stratified and sensitivity analyses. We included 3040 patients initiating treatment with GLP-1RA and 11,627 with SGLT-2i. When compared with patients treated with SGLT-2i, those in the GLP-1RA group were younger (55 vs 60 years old, p<0.001), had more anxiety (49.4% vs 41.5%, p<0.001), sleep disorders (43.2% vs 34.1%, p<0.001) and depression (24.4% vs 19.0%, p<0.001), and were more obese (35.1% of individuals with BMI ≥40 vs 15.1%, p<0.001). After propensity score weighting, standardised mean differences between groups were <0.1 for all covariates, showing adequate balance between groups at baseline after adjustment. In the main per-protocol analyses we found no evidence that GLP-1RA increased the incidence of SIS (HR 1.04; 95% CI 0.35, 3.14). Intention-to-treat analyses resulted in an HR of 1.36 (95% CI 0.51, 3.61). In analyses excluding individuals with no BMI information and using imputation for BMI missing values, respective HRs were 0.89 (95% CI 0.26, 3.14) and 1.29 (95% CI 0.42, 3.92). Stratified analyses showed no differences between subgroups. Our findings do not support an increased risk of SIS when taking GLP-1RA in individuals with type 2 diabetes and obesity; however, the rarity of SIS events and the wide uncertainty of effect size (although null, effect may be compatible with a risk as high as threefold) calls for a cautious interpretation of our results. Further studies, including final evaluations from regulatory bodies, are called for to discard a causal link between GLP-1RA and suicidality.

The effect of hsCRP on TyG index-associated cardiovascular risk in patients with acute coronary syndrome undergoing PCI

The effect of systemic inflammation, represented by high-sensitivity C-reactive protein (hsCRP), on triglyceride glucose (TyG) index-associated cardiovascular risk in patients with acute coronary syndrome (ACS) undergoing percutaneous coronary intervention (PCI) has not yet been determined. This study was a retrospective analysis of a single-center prospective registry and finally included 1701 patients (age, 60 ± 10 years; male, 76.7%). The primary endpoint was defined as major adverse cardiovascular events (MACE), including cardiovascular mortality, non-fatal stroke, and non-fatal myocardial infarction. In the multivariate COX regression model that included the GRACE risk score, higher TyG index was significantly associated with a greater incidence of MACE in patients with hsCRP levels less than 2 mg/L but not 2 mg/L or more (P for interaction = 0.039). Each unit increase in the TyG index was independently associated with a 52% increased risk of MACE only in patients with hsCRP levels less than 2 mg/L (P = 0.021). After adjustment for other confounding factors, including the GRACE risk score, compared with those in the group of TyG index < 8.62 and hsCRP < 2 mg/L, patients in the group of TyG index ≥ 8.62 and hsCRP ≥ 2 mg/L had a 3.9 times higher hazard ratio for developing MACE. The addition of both TyG index and hsCRP had an incremental effect on the predictive ability of the GRACE risk score-based prognostic model for MACE (C-statistic: increased from 0.631 to 0.661; cNRI: 0.146, P = 0.012; IDI: 0.009, P < 0.001). In conclusion, there was a significant interaction between the TyG index and hsCRP for the risk of MACE, and the TyG index was reliably and independently associated with MACE only when hsCRP levels were less than 2 mg/L. Furthermore, high TyG index and high hsCRP levels synergistically increased the risk of MACE, suggesting that the prognostic value of TyG index combined with hsCRP might be promising in patients with ACS undergoing PCI.

46 Radiological tumor burden is an independent risk factor for survival in patients with metastatic clear cell renal cell carcinoma (mccRCC) treated with first line immunotherapy (IO)-based regimens

Abstract Background IO-based regimens (IO + IO or IO + VEGF inhibitor) represent current standard of care systemic therapies for the management of patients with mRCC. IMDC is the current standard to assess prognosis in patients with mRCC of clear cell histology. Baseline radiological tumor burden (BRTB) is a readily available measurement to calculate using routine CT-scans. Here we describe the utility of BRTB as prognostic factor in patients with mccRCC treated with first line IO-based regimens. Methods We reviewed data of 183 patients with mccRCC treated at Dana-Farber Cancer Institute from August 2014 to October 2023 and who received ≥ 1 dose of an IO-based regimen (IO + IO or IO + VEGF inhibitor). Patients with available CT-scan reports within 1 month prior to first line treatment initiation were included in our analysis. BRTB was assessed by a single operator as the sum of all measurable lesions as listed on the RECIST v1.1 report. The primary outcome was overall survival (OS), and secondary outcomes were time to treatment failure (TTF) and time to next therapy (TTNT). To evaluate the impact of BRTB on OS, TTF and TTNT, we used univariable and multivariable Cox regression models accounting for IMDC risk group, history of nephrectomy, and presence of either bone, liver, or brain metastases prior to first line initiation. Results A total of 150 patients satisfied the inclusion criteria and were included in our final analysis, of which 80% of patients were male (120/150). 9% (13/150) had favorable risk, 51% (77/150) had intermediate risk and 20% (30/150) had poor risk by IMDC criteria. Overall, 73% (109/150) of patients had nephrectomy prior to first line therapy initiation and 41% (61/150) had either brain, bone, or liver metastasis. Median follow-up was 44.8 months. Every 1 cm increase in BRTB was associated with a 5% increase in risk of death (HR: 1.05; 95% CI: 1.03 – 1.08; p &amp;lt; 0.0001). On multivariable analysis, radiological tumor burden was significantly associated with OS (HR: 1.04; 95%CI: 1.00 – 1.08; p = 0.03). After categorizing BRTB by tertiles, tertile 1 included 0 - 7.5 cm, tertile 2: 7.6– 15.3 cm and tertile 3: 15.4 – 47.7 cm. The 4-year OS estimates were 84% (95%CI: 74 – 97%), 60% (95%CI: 45 – 81%) and 43% (95%CI: 29 – 66%), respectively, for the 1st, 2nd and 3rd tertile (log-rank P &amp;lt; 0.0001). BRTB did not show a significant association with TTF on univariable (HR: 1.00; 95%CI: 0.99 – 1.01; p = 0.783), or multivariable analysis (HR: 0.99; 95%CI: 0.97 – 1.01; p = 0.428). As for TTNT, BRTB also did not show a significant association on univariable (HR: 1.01; 95%CI: 1.0 – 1.02; p = 0.234) or multivariable analysis (HR: 1.01; 95%CI: 0.99 – 1.03; p = 0.453). Conclusions Baseline radiological tumor burden is an independent prognostic factor for OS in patients with mccRCC treated with first line immunotherapy-based regimens. However, tumor burden is not significantly associated with TTF or TTNT. Figure: Kaplan-Meier curves representing OS based on baseline radiological tumor burden assessed by RECIST v1.1 (Tertile 1: 0 - 7.5 cm; Tertile 2: 7.6 - 15.3 cm; Tertile 3: 15.4 – 47.7 cm). P value is derived from the log-rank test.

GLIM criteria validation and reliability in critically ill patients with cancer: A prospective study.

The present study aims to assess the interrater reliability of the Global Leadership Initiative on Malnutrition (GLIM) criteria, a framework to provide a consensus diagnosis of malnutrition. We also aimed to investigate its concurrent and predictive validity in the context of patients with cancer admitted to the intensive care unit (ICU). Individuals aged ≥19 years with cancer who were admitted to the ICU within 48 h of their initial hospital admission were included. Nutrition status was assessed with the Nutritional Risk Screening 2002, the Subjective Global Assessment (SGA), and the GLIM criteria. Interrater reliability was assessed by the kappa test (>0.80). The SGA served as the established benchmark for assessing concurrent validity. To evaluate predictive validity, the occurrence of mortality within 30 days was the outcome, and Cox regression models were applied. A total of 212 patients were included: 66.9% were at nutrition risk, and 45.8% were malnourished according to the SGA. According to the GLIM criteria, 68.4% and 66% were identified as malnourished by evaluators 1 and 2, respectively (κ = 0.947; P < 0.001). The GLIM combination incorporating weight loss and the presence of inflammation exhibited sensitivity (82.4%) and specificity (92%). In the multivariate Cox regression models, most GLIM combinations emerged as independent predictors of complications. The GLIM criteria demonstrated satisfactory interrater reliability, and the combination involving weight loss and the presence of inflammation exhibited noteworthy sensitivity and specificity. Most GLIM combinations emerged as independent predictors of 30-day mortality.

A New Ferroptosis-Related Long Non-Coding RNA Risk Model Predicts the Prognosis of Patients With Papillary Thyroid Cancer.

Ferroptosis is a novel form of regulated cell death that involves in cancer progression. However, the role of ferroptosis-related long non-coding RNAs (lncRNAs) in papillary thyroid cancer (PTC) remains to be elucidated. The purpose of this paper was to clarify the prognostic value of ferroptosis-related lncRNAs in PTC. The transcriptome data and clinical information were downloaded from The Cancer Genome Atlas (TCGA) database. The correlation between ferroptosis-related genes (FRGs) and lncRNA was determined using Pearson correlation analysis. Multivariate Cox regression model (P < 0.01) was performed to establish a ferroptosis-related lncRNAs risk model. Kaplan-Meier survival analysis, receiver operating characteristic (ROC) curves, risk curve and nomograms were then performed to assess the accuracy and clinical applicability of prognostic models. The correlations between the prognosis model and clinicopathological variables, immune and m6A were analyzed. Finally, in vitro assays were performed to verify the role of LINC00900, LINC01614 and PARAL1 on the proliferation, migration and invasion in TPC-1 and BCPAP cells, as well as the relationship between three lncRNAs and ferroptosis. A five-ferroptosis-related lncRNAs (PARAL1, LINC00900, DPH6-DT, LINC01614, LPP-AS2) risk model was constructed. Based on the risk score, samples were divided into the high- and low-risk groups. Patients in the low-risk group had better prognosis than those in high-risk group. Compared to traditional clinicopathological features, risk score was more accurate in predicting prognosis in patients with PTC. Additionally, the difference of immune cell, function and checkpoints was observed between two groups. Moreover, experiments showed that LINC00900 promoted the proliferation, migration and invasion in TPC-1 and BCPAP cells, while LINC01614 and PARAL1 revealed opposite effects, all of which were related to ferroptosis. In summary, we identified a five-ferroptosis-related lncRNAs risk model to predict the prognosis of PTC. Furthermore, our study also revealed that LINC00900 functioned as a tumor suppressor lncRNA, LINC01614 and PARAL1 as an oncogenic lncRNA in PTC.

Impact of PM2.5 exposure in old age and its interactive effect with smoking on incidence of diabetes

PurposeTo determine the impact of PM2.5 exposure in old age and its interactive effect with smoking on incident diabetes. MethodsA total of 2766 participants aged ≥60 years in China were interviewed at baseline for disease risk factors in 2001–03 and were then followed up for 10 years to document incident diabetes. They were assessed for daily PM2.5 exposure in 2005. Multivariate Cox regression models were used to examine the association of PM2.5 exposure with incident diabetes and interactive effect between PM2.5 and smoking on incident diabetes. ResultsDuring the cohort follow-up, 176 participants developed diabetes. The incidence of diabetes increased with PM2.5 exposure; the multiple-adjusted hazard ratio (HR) of diabetes was 2.27 (95 % CI 1.36–3.77) in participants with PM2.5 at ≥62.0 μg/m3 compared to those with <62.0 μg/m3. There was a significant interaction effect of PM2.5 with smoking on increased risk of diabetes. The adjusted HR for participants exposed to PM2.5 levels ≥62.0 μg/m3 who smoked was 4.39 (95 % CI 1.72–11.21), while for non-smokers it was 1.65 (95 % CI 0.88–3.09), compared to those with <62.0 μg/m3. ConclusionsExposure to PM2.5 in old age was associated with an increased incidence of diabetes and smoking enhanced the impact of PM2.5 on diabetic risk. These findings underscore the urgent need for air quality improvement measures and smoking cessation programs to mitigate the risk of diabetes in aging populations.

Exploring the Association Between Heart Rate Control and Rehospitalization: A Real-World Analysis of Patients Hospitalized with Heart Failure with Reduced Ejection Fraction.

In patients with heart failure with reduced ejection fraction (HFrEF), lower discharge heart rate (HR) is known to be associated with better outcomes. However, the effect of HR control on patient outcomes, and the demographic and clinical determinants of this association, are not well documented. The purpose of this work was to evaluate the association between the HR control and the risk of post-discharge rehospitalization in patients hospitalized with HFrEF. Data were collected using a retrospective medical record review in the USA. Reduction in HR between admission and discharge ("HR control") defined the primary exposure, categorized as no reduction, > 0 to < 20% reduction, and ≥ 20% reduction. Time to first rehospitalization in the post-discharge follow-up defined the study outcome and was analyzed using multivariable Cox regression modeling. A total of 1002 patients were analyzed (median age, 63 years; median follow-up duration, 24.2 months). At admission, 59.1% received beta-blockers, 57.4% received diuretics, and 47.5% received angiotensin-converting enzyme (ACE) inhibitors. Most patients (90.5%) achieved some HR control (38.4% achieved > 0 to < 20% reduction, and 52% achieved ≥ 20% reduction). Approximately 39% were rehospitalized during the follow-up (14% within 30 days). In multivariable analysis, patients with > 0 to < 20% reduction in HR had a 39% lower risk of rehospitalization [hazard ratio 0.61; 95% confidence interval (CI) 0.43-0.85]; patients with ≥ 20% reduction in HR had a 38% lower rehospitalization risk (hazard ratio 0.62; 95% CI 0.45-0.87) than those with no HR reduction. Reduction in HR between admission and discharge was associated with reduced risk for rehospitalization. Findings indicate HR control as an important goal in the management of patients hospitalized for HFrEF.

Missed Follow-up is associated with worse survival in stage I lung cancer: results from a large multi-site academic hospital system

The purpose of this study is to examine the effect of early incomplete follow-up on overall survival among stage I lung cancer patients. Patients with clinical stage I lung cancer at our institution between 2007 and 2016 were identified (N = 1111). Exclusions included < 18 years of age (N = 2), missing stage or demographics (N = 56), incomplete appointment data or had only one scheduled appointment (N = 351), or did not survive for at least 1 year after diagnosis (N = 120). Missed appointments were defined as unattended follow-up appointments within the first year of diagnosis without an attended appointment in the subsequent 60 days. The primary outcome was the hazard ratio (HR) for death associated per 10% increase in missed oncology follow-up appointments. Univariable and descriptive statistics were performed, and a multivariable landmark Cox regression model was created to examine the effect of missed oncology follow-up on survival. A total of 582 patients were analyzed with median follow-up of 3.2 years and median age of 69 years. On multivariable analysis controlling for age, sex, race, insurance status, and definitive treatment type the HR for death was 1.44 (95% CI 1.05–1.97) for every 10% increase in missed appointments. Incomplete oncologic follow-up may negatively impact overall survival among survivors of early-stage lung cancer.

The Impact of D2 Versus D1 Lymphadenectomy in Siewert II Gastroesophageal Junction (GEJ) Cancer.

Although multiple treatment options exist for gastroesophageal junction (GEJ) cancer, surgery remains the mainstay for potential cure. Extended nodal dissection with a D2 lymphadenectomy (LAD) remains controversial for Siewert II GEJ cancer. Although D2 LAD may lead to a greater lymph node harvest, its effect on survival remains elusive. The authors hypothesized that additional D2 dissection in Siewert II GEJ cancer does not lead to increased survival. This study reviewed Siewert II patients who received a D1 or D2 LAD in addition to minimally invasive esophagectomy (MIE) after receiving neoadjuvant chemoradiation or perioperative chemotherapy (2012-2022). The patients were followed for up to 5 years. The outcomes measured were survival, number of nodes sampled, and operative time. The association between D1 or D2 LAD and overall survival was analyzed with Kaplan-Meier methods and a multivariable Cox regression model. Among 155 patients, 74 % underwent D1 and 26 % underwent D2 LAD. The patients with D2 had more than 15 lymph nodes harvested more frequently than those who had D1 (83 % vs 48 %; p < 0.001), with no difference in positive nodes (2.8 ± 5.2 vs 2.1 ± 4.2; p = 0.4). The patients with D2 LAD had a longer median operative time than those who with D1 LAD (362 vs 244 min; p < 0.001). In Kaplan-Meier and multivariable Cox regression models, overall survival differed significantly between the patients undergoing D2 and those who had D1 (adjusted hazard ratio [aHR], 0.52; 95 % confidence interval [CI], 0.25-1.00; p = 0.067). Little consensus exists regarding the optimal lymph node harvest for GEJ cancers. In Siewert II cancer, D2 LAD may not be mandatory and may lead to increased operative morbidity with no significant difference in survival.

Baseline weight recovery and mortality risk in head and neck cancer.

As a surrogate of malnutrition, degree of weight loss and recovery from head and neck cancer (HNC) treatment is understudied. The influence of modifiable factors that affect weight, including speech/language pathology (SLP) and nutrition counseling, is also poorly defined. We characterize weight loss trends, baseline weight recovery (BWR), and the impact of interdisciplinary care on oncologic outcomes. Retrospective cohort study assessing 266 newly diagnosed patients with HNC who completed curative-intent radiation (definitive or adjuvant) between January 2016 to January 2022. Relevant treatment factors were analyzed using multivariable Cox regression models. Altogether, 266 patients completed full-course radiation therapy (RT), encompassing definitive chemoRT (53.0%), surgery with chemoRT (18.4%), surgery with RT (17.7%), and RT alone (10.9%). Patient weight reached a nadir at median 3.0 months (IQR 3.0-11.3) after radiation, with a median weight loss of 12.6% (IQR 7.9-18.7). Notably, only 47.4% exhibited BWR. For those who recovered, median time to BWR was 10.5 months (IQR 3.0-24.0). On multivariable analysis, BWR by 6 months was significantly associated with overall survival (HR 0.28 [95% CI 0.10-0.76], p = 0.013), as was SLP consultation (HR 0.40 [95% CI 0.17-0.92], p = 0.031) and nutrition consultation (HR 0.34 [95% CI 0.13-0.89], p = 0.028). A high proportion of patients with HNC fail to recover baseline weight after treatment; those that do can take longer than expected to return. Failure to recover baseline weight is associated with a notable decrease in survival. Similarly, SLP and nutrition consultation are independent, modifiable determinants correlated with outcomes, supporting the emphasis on multidisciplinary management. Measures to promote BWR may reduce mortality.

Long-term efficacy and prognostic factors of Beijing Children's Hospital-2009-lymphoblastic lymphoma in the treatment of T-lymphoblastic lymphoma in children and adolescents

Objective: To summarize the long-term efficacy of Beijing Children's Hospital-2009-lymphoblastic lymphoma (BCH-2009-LBL) in the treatment of T-lymphoblastic lymphoma (T-LBL) in children and adolescents and to explore the prognostic factors. Methods: T-LBL children admitted to Beijing Children's Hospital Affiliated to Capital Medical University from January 2009 to April 2017 were retrospectively included. According to clinical stage, prognostic genes and treatment response, the children were divided into low, intermediate and high risk groups, and stratified treatment was performed according to the BCH-2009-LBL protocol, with follow-up until December 31, 2023. The clinical characteristics and therapeutic effect of each group were compared. Survival curve was drawn by Kaplan-Meier method, and the difference in survival rate between groups was compared by log-rank test. Multivariate Cox regression model was used to analyze the prognostic factors. Results: A total of 146 patients were included, the age of disease onset [M(Q1, Q3)] was 8.0 (1.5, 14.0) years old. There were 107 (73.3%) males and 39 (26.7%) females. Clinical staging: 1 case in stage Ⅰ and 1 case in stage Ⅱ (0.7% each), 41 cases (28.1%) cases in stage Ⅲ and 103 cases(70.5%) in stage Ⅳ. There were 1 case (0.7%), 93 cases (63.7%), and 52 cases (35.6%) in the low, intermediate, and high-risk groups, respectively. The follow-up time was 121 (80, 180) months, and the 5-year and 10-year event-free survival (EFS) rates were 76.4% and 75.0%, respectively. The 5-year EFS rates of low, intermediate and high risk groups were 100.0%, 81.3% and 67.3%, respectively. There was significant difference in remission between the middle-risk group and the high-risk group on the 8th day of hormone pretreatment and at the end of induction (both P<0.05). Recurrence/progression occurred in 29 cases (recurrence rate 19.9%), and the recurrence time was 15 (3, 74) months, in which 26 cases died and only 3 cases survived. Infection-related death occurred in 6 cases (4.1%). The failure or progression of hormone pretreatment at d8 (HR=10.089, 95%CI: 1.266-80.387, P=0.029) and the failure to achieve complete remission at the end of induction (mid-term evaluation) (HR=7.638, 95%CI: 2.411-24.199, P=0.001) were the risk factors for EFS rate of intermediate risk group. The above indexes had no statistical significance on EFS rate in high-risk groups (all P>0.05). Conclusions: BCH-2009-LBL regimen shows good efficacy in the treatment of pediatric T-LBL. The failure or progression of hormone pretreatment at d8 and the failure to achieve complete remission at the end of induction (mid-term evaluation) were the risk factors for EFS rate.

Interim efficacy of a multicenter cohort study for China Net Childhood Lymphoma mature B-cell lymphoma 2017 regimen in the treatment of pediatric High-grade-B cell lymphoma

Objective: To analyze the mid-term efficacy of the China Net Childhood Lymphoma mature B-cell lymphoma 2017 (CNCL-B-NHL-2017) regimen in treating children with high-grade B-cell lymphoma (HGBL). Methods: Clinical and pathological data of HGBL children aged≤18 years admitted to 16 hospitals of the Chinese Children's Lymphoma Collaborative Group (CNCL) from May 2017 to April 2021 were collected retrospectively. They were divided in to high-grade B-cell lymphoma with double hit/triple hit (HGBL-DH/TH) group and high-grade B-cell lymphoma non-specified (HGBL-NOS) group, according to the 2016 version of the World Health Organization (WHO) Hematopoietic and Lymphoid Tissues Cancer Classification. Both groups of patients were treated with stratified chemotherapy by risk according to the CNCL-B-NHL-2017 scheme. The deadline for follow-up was December 31, 2023. All the patients were examined by chromosome fluorescence in situ hybridization (FISH), and the rearrangement of genes MYC, BCL-2 and BCL-6 was confirmed. The clinical and pathological characteristics of patients at disease onset were analyzed, and the therapeutic effects of patients in different clinical stages and risk groups were compared. Survival analysis was drawn by Kaplan Meier method, the log-rank test was used to compare the differences in the cumulative survival rate between different groups, and multivariate Cox regression model was used to identify the prognostic factors. Results: A total of 62 patients were included, with an onset age [M(Q1, Q3)] of 7 (4, 11) years, including 48 males and 14 females. There were 11 (17.7%) patients in stageⅡ, 33(53.2%)patients in stage Ⅲ and 18(29.1%)patients in stage Ⅳ. FISH testing showed that 4 cases (6.5%) were HGBL-DH and 3 (4.8%) were HGBL-TH. The remaining 55 cases (88.7%) were HGBL-NOS, with 18 cases accompanied by MYC rearrangement. There were 7 cases in the HGBL-DH/TH group and 55 cases in the HGBL-NOS group. Thirteen cases (20.9%) were treated with the B1 regimen, 3 cases (4.8%) with B2 regimen, 37 cases (59.6%) with C1 regimen, and 9 cases (14.7%) with the C2 regimen. Forty-eight cases (77.4%) received rituximab therapy at the same time. Five cases (8.0%) progressed during treatment. The follow-up time [M(Q1, Q3)] was 43.5 (36.1, 53.7) months. The complete remission rate was 91.9% (57/62). The 3 year overall survival rate was 93.5% and event-free survival (EFS) rate was 91.9%. The 3-year overall survival rate in the HGBL-NOS group was higher than that in the HGBL-DH/TH group (96.3% vs 71.4%, P=0.011). The 3-year EFS rate of the HGBL-NOS group was higher than that of the HGBL-DH/TH group (94.5% vs 71.4%, P=0.037). In the HGBL-NOS subgroup, the overall survival rate of children with MYC rearrangement was lower (100% vs 88.9%,P=0.039). Multivariate Cox regression analysis showed that central invasion (HR=6.05, 95%CI: 1.96-38.13, P=0.046) was a risk factor for overall survival. Conclusion: CNCL-B-NHL-2017 regimen shows significant effects in the treatment of pediatric HGBL, with a good prognosis.

Immune landscape of hepatocellular carcinoma: The central role of TP53-inducible glycolysis and apoptosis regulator.

This study aims to address the substantive issue of lacking reliable prognostic biomarkers in hepatocellular carcinoma (HCC) by investigating the relationship between TP53-inducible glycolysis and apoptosis regulator (TIGAR) and HCC prognosis using The Cancer Genome Atlas database. (1) Integrated statistical analyses, including logistic regression, Wilcoxon signed-rank test, and Kruskal-Wallis test, were conducted to explore the association between TIGAR expression and clinical-pathological features of HCC. (2) The Kaplan-Meier method combined with univariate and multivariate Cox regression models underscored TIGAR as a prognostic factor in HCC. (3) Gene set enrichment analysis (GSEA) revealed key pathways associated with TIGAR, while single-sample gene set enrichment analysis (ssGSEA) determined its relevance to cancer immune infiltration. (1) Elevated TIGAR expression was significantly correlated with decreased survival outcomes in HCC patients. (2) GSEA highlighted the significant link between TIGAR and humoral immunity. (3) ssGSEA revealed a positive correlation between TIGAR expression and infiltration of Th1 and Th2 cells and a negative correlation with Th17 cell infiltration. TIGAR, as a potential prognostic biomarker for HCC, holds significant value in immune infiltration. Understanding the role of TIGAR could contribute to improved prognostic predictions and personalized treatment strategies for HCC patients.

Left Ventricular Mass as a Modulator of Ventricular Arrhythmia Risk and Sex Differences Following CRT for Non-Ischemic Cardiomyopathy and LBBB

Risk for ventricular arrhythmias (VA) following cardiac resynchronization therapy (CRT) has been associated with ischemic disease/scar, sex, and possibly left ventricular mass (LVM). To evaluate sex differences and baseline/post-implant change [Δ] of LVM on VA risk after CRT implant among patients with non-ischemic cardiomyopathy (NICM) and left bundle branch block. Among patients meeting the criteria, baseline and follow-up echocardiographic images were obtained for LVM assessment. VA events were reported from device diagnostics and therapies. VA risk was stratified by ROC (Youden-index cut-point) for baseline LVM and ΔLVM, and baseline patient characteristics using a multivariable Cox regression model. 118 patients (71[60.2%] female, age 60.5 ±11.3 years, LVEF 19.2 ±7.0%, QRS 165.6 ±20 ms, LVM 313.9 ±108.8 g) were enrolled and followed for median 90 (IQR 44-158) months. Thirty-five (29.6%) patients received appropriate shocks or anti-tachycardia pacing at a median of 73.5 (IQR 25-130) months post-implant. Males had a higher VA incidence (male 18/47 [38.3%] vs. female 17/71 [23.9%], P=0.02). Baseline LVM >308.9g separated patients with higher VA risk (P=0.001). Less than a 20% decrease in LVM increased VA risk (P<0.001). Baseline LVM was the only baseline characteristic predicting VA events in the Cox regression model (Hazard ratio 1.01 [95%CI, 1.001-1.009], Log-rank P=0.003). Sex differences in VA risk were eliminated by the baseline LVM parameters. VA risk after CRT in NICM was associated with baseline LV >308.9g and a decrease in LVM ≤ 20%, without sex differences.

The obesity paradox and 90 day mortality in chronic critically ill patients: a cohort study using a large clinical database

BackgroundThis study investigates the obesity paradox, where obesity is linked to lower mortality in certain patient groups, focusing on its impact on long-term mortality in chronic critically ill (CCI) patients.MethodsWe retrospectively analyzed CCI patients from the Medical Information Mart for Intensive Care-IV (MIMIC-IV) database’s Intensive Care Unit, categorizing them into six groups based on Body Mass Index (BMI). Using stepwise multivariable Cox regression and restricted cubic spline models, we examined the association between BMI and 90 day mortality, accounting for confounding variables through subgroup analyses.ResultsThe study included 1996 CCI patients, revealing a 90 day mortality of 34.12%. Overweight and obese patients exhibited significantly lower mortality compared to normal-weight individuals. Adjusted analysis showed lower mortality risks in overweight and obese groups (HRs 0.60 to 0.72, p < 0.001). The cubic spline model indicated a negative correlation between BMI and 90 day mortality, with subgroup analyses highlighting interactions with age.ConclusionOur findings confirm the obesity paradox in CCI patients, especially among the elderly (65–85 years) and very elderly (≥ 85 years). The results suggest a beneficial association of higher BMI in older CCI patients, though caution is advised for those under 45.

Correlation between abdominal computed tomography signs and postoperative prognosis for patients with colorectal cancer.

Patients with different stages of colorectal cancer (CRC) exhibit different abdominal computed tomography (CT) signs. Therefore, the influence of CT signs on CRC prognosis must be determined. To observe abdominal CT signs in patients with CRC and analyze the correlation between the CT signs and postoperative prognosis. The clinical history and CT imaging results of 88 patients with CRC who underwent radical surgery at Xingtan Hospital Affiliated to Shunde Hospital of Southern Medical University were retrospectively analyzed. Univariate and multivariate Cox regression analyses were used to explore the independent risk factors for postoperative death in patients with CRC. The three-year survival rate was analyzed using the Kaplan-Meier curve, and the correlation between postoperative survival time and abdominal CT signs in patients with CRC was analyzed using Spearman correlation analysis. For patients with CRC, the three-year survival rate was 73.86%. The death group exhibited more severe characteristics than the survival group. A multivariate Cox regression model analysis showed that body mass index (BMI), degree of periintestinal infiltration, tumor size, and lymph node CT value were independent factors influencing postoperative death (P < 0.05 for all). Patients with characteristics typical to the death group had a low three-year survival rate (log-rank χ 2 = 66.487, 11.346, 12.500, and 27.672, respectively, P < 0.05 for all). The survival time of CRC patients was negatively correlated with BMI, degree of periintestinal infiltration, tumor size, lymph node CT value, mean tumor long-axis diameter, and mean tumor short-axis diameter (r = -0.559, 0.679, -0.430, -0.585, -0.425, and -0.385, respectively, P < 0.05 for all). BMI was positively correlated with the degree of periintestinal invasion, lymph node CT value, and mean tumor short-axis diameter (r = 0.303, 0.431, and 0.437, respectively, P < 0.05 for all). The degree of periintestinal infiltration, tumor size, and lymph node CT value are crucial for evaluating the prognosis of patients with CRC.

Acute changes in kidney function and outcomes following an acute myocardial infarction: Insights from PARADISE-MI.

Pharmacologic blockade of neurohormonal pathways in patients with acute myocardial infarction (MI) can result in acute changes in biomarkers of kidney function. We evaluated the effect of sacubitril/valsartan versus ramipril on initial changes in serum creatinine and the association of these changes with longer-term outcomes among participants in PARADISE-MI. In this randomized, double-blind, active-controlled, event-driven trial, 5661 patients with an acute MI were assigned to receive sacubitril/valsartan or ramipril, with no run-in. The frequency of an initial pre-specified increase in serum creatinine (≥26.5 or ≥44 μmol/L) from baseline to week 1 was compared between arms. Multivariable Cox regression models were fit to examine the association of acute changes in serum creatinine with the primary cardiovascular composite outcome (cardiovascular death, first heart failure hospitalization, or outpatient heart failure), all-cause mortality, and longer-term changes in estimated glomerular filtration rate (eGFR). An initial increase in serum creatinine ≥26.5 μmol/L occurred in 155 of 2604 (6.0%) patients assigned to sacubitril/valsartan and 120 of 2603 (4.6%) patients assigned to ramipril (odds ratio [OR] 1.32; 95% confidence interval [CI] 1.03-1.68). The corresponding numbers for an increase ≥44 μmol/L were 57 (2.2%) and 42 (1.6%), respectively (OR 1.37; 95% CI 0.92-2.05). A higher odds of increased serum creatinine ≥26.5 and ≥44 μmol/L for sacubitril/valsartan versus ramipril appeared to be restricted to patients who had a greater decline in systolic blood pressure over the same period (p-interaction = 0.05 and 0.001, respectively). In multivariable analyses, neither an acute increase in serum creatinine ≥26.5 or ≥44 μmol/L was associated with a higher risk of cardiovascular outcomes, all-cause mortality, or differences in longer-term eGFR slope. Findings were similar across the randomized treatment arms (p-interaction >0.6 for all). Following acute MI, patients assigned to sacubitril/valsartan had a higher frequency of initial increases in serum creatinine at 1 week, compared with ramipril. In adjusted models, initial increases in serum creatinine with either treatment were not associated with adverse cardiovascular outcomes or changes in longer-term kidney function.

An internally and externally validated nomogram for predicting cancer-specific survival in octogenarians after radical resection for colorectal cancer

AimsWe aimed to develop an elaborative nomogram that predicts cancer-specific survival (CSS) in American and Chinese octogenarians treated with radical resection for CRC.MethodsThe patient data of newly diagnosed patients aged 80 years or older who underwent radical resection for CRC from 2010 to 2015 were extracted from the Surveillance, Epidemiology, and End Results (SEER) database and then randomly divided into a training cohort and a validation cohort. The patients collected from our hospital were defined as the external validation cohort. Univariate and multivariate Cox regression was used to select independent predictive factors for the construction of a nomogram to predict 1-, 2- and 3-year CSS.ResultsThe multivariate Cox regression model identified age, T stage, N stage, perineural invasion, chemotherapy, tumour deposits, carcinoembryonic antigen level, number of lymph node metastases, and number of solid organ metastases as independent predictors of survival. The C-index of the nomogram for 1-, 2- and 3-year CSS was 0.758, 0.762, and 0.727, respectively, demonstrating significant clinical value and substantial reliability compared to the TNM stage. The calibration curve and area under the curve also indicated considerable predictive accuracy. In addition, decision curve analysis demonstrated desirable net benefits in clinical application.ConclusionWe constructed a nomogram for predicting the CSS of individual octogenarian patients with CRC who underwent radical resection. The nomogram performed better than the TNM staging system in this particular population and could guide clinicians in clinical follow-up and individual therapeutic plan formulation.

Association of gum treatment with cognitive decline and dementia risk among older adults with periodontal symptoms: a 12-year prospective cohort study.

This study examines the associations of gum treatment with cognitive decline and dementia risk among older adults with periodontal symptoms in the US. A cohort of 866 adults aged ≥50 with periodontal symptoms was recruited for the 2008 Health and Retirement Study "Dental Health Experimental Module" and followed until 2020. Cognitive function was assessed with the Telephone Interview for Cognitive Status (TICS). Dementia status was ascertained with the Langa-Weir algorithm based on TICS scores and proxy assessments. Linear mixed-effects model and multivariable Cox regression models were utilized to analyze the associations of gum treatment with cognitive decline and the risk of dementia, respectively. Of 866 participants (mean age 67.7, 61.4% women), 105 (12.1%) developed dementia with a median 9 (IQR, 6-10) years follow-up. The dementia incidence rates were lower in the group with gum treatment (7.4 vs. 12.9 per 1,000 person-years). Compared with participants who did not have gum treatment, those with gum treatment experienced a decline in TICS score that was on average 0.025 (95% CI, 0.005-0.044) points less per year and a 38% lower incidence of dementia (Hazard Ratio, 0.62; 95% CI, 0.41-0.93). These associations were consistent across participants with different severity of periodontal symptoms and sociodemographic characteristics (age, sex, race, ethnicity, and education) except for income levels. Prompt gum treatment for older adults with periodontal symptoms may be beneficial for their cognitive health.

The association between preoperative serum cholinesterase and all-cause mortality in geriatric patients with hip fractures: a cohort study of 2387 patients

ObjectiveThis study is to evaluate the association between preoperative cholinesterase levels and all-cause mortality in geriatric hip fractures.MethodsElderly patients with hip fractures were screened between Jan 2015 and Sep 2019. Demographic and clinical characteristics of patients were collected. Linear and nonlinear multivariate Cox regression models were used to identify the association between preoperative cholinesterase levels and mortality in these patients. Analyses were performed using EmpowerStats and the R software.ResultsTwo thousand three hundred eighty-seven patients were included in this study. The mean follow-up period was 37.64 months. Seven hundred eighty-seven (33.0%) patients died due to all-cause mortality. Preoperative cholinesterase levels were 5910 ± 1700 U/L. Linear multivariate Cox regression models showed that preoperative cholinesterase level was associated with mortality (HR = 0.83, 95% CI: 0.78–0.88), P < 0.0001) for every 1000 U/L. However, the linear association was unstable, and nonlinearity was identified. A cholinesterase concentration of 5940 U/L was an inflection point. When preoperative cholinesterase level < 5940 U/L, the mortality decreased by 28% for every 1000 U/L increase in cholinesterase (HR = 0.72, 95%CI: 0.66–0.79, P < 0.0001). When cholinesterase was > 5940 U/L, the mortality was no longer decreased with the rise of cholinesterase (HR = 1.01, 95%CI: 0.91–1.11, P = 0.9157). We found the nonlinear association was very stable in the propensity score-matching sensitive analysis.ConclusionsPreoperative cholinesterase levels were nonlinearly associated with mortality in elderly hip fractures, and cholinesterase was a risk indicator of all-cause mortality.Trial registrationThis study is registered on the website of the Chinese Clinical Trial Registry (ChiCTR: ChiCTR2200057323) (08/03/2022).