Cox Regression Research Articles

Association between waist triglyceride index, body mass index, dietary inflammatory index, and triglyceride- glucose index with chronic kidney disease: the 1999-2018 cohort study from NHANES

PurposeTo compare the dietary inflammatory index (DII), triglyceride glucose index (TyG), waist triglyceride index (WTI), and body mass index (BMI) in predicting the survival of chronic kidney disease (CKD).MethodologyInclusion of 23,099 participants from the NHANES database who met specific criteria. Baseline was established using quartiles of DII index. The relationship between DII index, WTI index, TyG index, and BMI index with mortality rate in CKD patients was evaluated using Kaplan-Meier curves. Univariate and multivariate COX regression risk models were used to study the relationship between DII index, WTI index, and TyG index with mortality risk in CKD patients. Stratification of eGFR by age and gender was conducted to investigate the association between DII index, WTI index, and TyG index with mortality risk in CKD patients. Restricted cubic spline analysis was used to study the correlation between DII index, WTI index, and TyG index with mortality risk in CKD patients.ResultsThe incidence of CKD increased with the increase of DII index, WTI index and TyG index. After multivariable adjustment, the fourth quartile of DII index, TyG index and WTI index showed the highest risk for CKD [DII: hazard ratio (HR) 1.36, 95% confidential interval (CI) (1.23–1.51); TyG: HR 1.21; 95% CI (1.07–1.37); WTI: HR 1.29; 95% CI (1.13–1.46)]. There was no difference in the risk of developing CKD between the obese group (BMI ≥24 kg/m2) and the normal weight group (P>0.05).ConclusionThis study has identified a significant association between elevated DII index, WTI index, and TyG index with the risk of CKD. Furthermore, the DII index demonstrated superior prognostic capability in predicting CKD compared to other indicators.

20 Evaluating intermediate endpoints for overall survival in metastatic renal cell carcinoma treated with immune checkpoint inhibitors: an IMDC study

Abstract Background In Phase 3 trials, the assessment for primary endpoint of overall survival (OS) necessitates extended follow-up periods, a larger pool of events, and higher associated costs. Hence, we sought to determine whether shorter intermediate (IEs) such as Objective Response (OR), Time to Treatment Failure (TTF) and Time to Next Therapy (TTNT) are associated with OS in patients receiving immune checkpoint (ICI)-based therapy. Methods We included all International mRCC Database Consortium (IMDC) patients who received contemporary first line(1L) ICI from 2013 to 2023. IEs were defined from ICI start until drug cessation or death for TTF, and initiation of next line or death for TTNT, or censored at date of last follow-up. OR included investigators-assessed complete or partial response per RECIST1.1 criteria. First, we assessed the endpoint correlations across all follow-up times of individual patient data using Kendall’s Tau (KT) correlation by a Clayton copula. A KT >0.49 indicates a strong correlation (Wicklin R., 2023). Then we evaluated associations of OS with TTF and TTNT status at the 6-month landmark using Cox regression adjusting for IMDC risk groups, metastatic sites, histology, age, and prior nephrectomy, stratified by ICI type and years of ICI start. The KT correlation was estimated by the R GJRM package (https://www.r-project.org/). All other statistical analyses were done with SAS 9.4 software (SAS Institute, Cary, NC). Results The cohort consisted of 1667 patients with a median follow-up of 15.4 months (IQR: 7.1-28.6). For the 6-month landmark analysis in OS, patients who died or had less than 6 months of follow-up were excluded, affecting 278 for OR, 373 for TTF, and 380 for TTNT. Median age at 1L start was 63 years (IQR: 56-70), with 73% being male and 65% undergoing nephrectomy before starting 1L. A total of 1132 patients received dual ICI, while 535 received an ICI+TKI combination. Over the entire follow-up of individual patient data, the Kendall’s Tau correlation was 0.49 (95%CI: 0.45-0.52) for TTF with OS and 0.67 (95%CI: 0.64-0.69) for TTNT with OS. The Kendall’s Tau correlations between endpoints were also similar in subgroup analyses by IMDC risk group and type of regimen and the strongest in the ICI+TKI subgroup with a Kendall’s Tau correlation of 0.73(0.66-0.78). On the 6-month OS landmark analysis (Table), patients who discontinued their 1L regimen had poor OS (adjusted HR: 2.77 (95%CI: 2.16-3.55)). Additionally, those who transitioned to a 2L therapy within the first 6 months showed worse OS, reflected by an HR of 2.82 (2.22-3.59). Patients who did not have an objective response also had worse OS (adjusted HR: 2.74 (95%CI: 2.15-3.49)). On the other hand, patients with an objective response had an 18-month OS rate (equivalent of 12-month OS post the 6-month landmark) of 91% (95%CI: 88%-93%) vs 74% (95%CI: 70%-78%) for those with no response at 6 months. Table. Landmark analysis of OS from 6 months of post therapy initiation, according to OR, TTF and TTNT event status at 6 months, in whole cohort and by IMDC and treatment groups. Conclusions Our study explored TTF, TTNT and OR as clinical IEs for OS. TTNT demonstrated the strongest association with OS, particularly in the ICI+TKI subgroup, making it a potentially clinically meaningful intermediate endpoint for evaluating treatment efficacy in ICI-based regimens.

Single-sample gene set enrichment analysis reveals the clinical implications of immune-related genes in ovarian cancer

PurposeOvarian cancer (OC) is a common gynecological malignancy with poor prognosis and substantial tumor heterogeneity. Due to the complex tumor immune microenvironment (TIME) among ovarian cancer, only a few patients have an immune response to immunotherapy. To investigate the differences in immune function and identify potential biomarkers in OC, we established a prognostic risk scoring model (PRSM) with differential expression of immune-related genes (IRGs) to identify critical prognostic IRG signatures.MethodsSingle-sample gene set enrichment analysis (ssGSEA) was used to investigate the infiltration of various immune cells in 372 OC patients. Then, COX regression analysis and Lasso regression analysis were used to screen IRGs and construct PRSM. Next, the immunotherapy sensitivity of different risk groups regarding the immune checkpoint expression and tumor mutation burden was evaluated. Finally, a nomogram was created to guide the clinical evaluation of the patient prognosis.ResultsIn this study, 320 immune-related genes (IRGs) were identified, 13 of which were selectively incorporated into a Prognostic Risk Scoring Model (PRSM). This model revealed that the patients in the high-risk group were characterized as having poorer prognosis, lower expression of immune checkpoints, and decreased tumor mutation load levels compared with those in the low-risk group. The nomogram based on the risk score can distinguish the risk subtypes and individual prognosis of patients with OC. Additionally, M1 macrophages may be the critical target for immunotherapy in OC patients.ConclusionWith the in-depth analysis of the immune microenvironment of OC, the PRSM was constructed to predict the OC patient prognosis and identify the subgroup of the patients benefiting from immunotherapy.

Atherosclerosis quantification and cardiovascular risk: the ISCHEMIA trial.

The aim of this study was to determine the prognostic value of coronary computed tomography angiography (CCTA)-derived atherosclerotic plaque analysis in ISCHEMIA. Atherosclerosis imaging quantitative computed tomography (AI-QCT) was performed on all available baseline CCTAs to quantify plaque volume, composition, and distribution. Multivariable Cox regression was used to examine the association between baseline risk factors (age, sex, smoking, diabetes, hypertension, ejection fraction, prior coronary disease, estimated glomerular filtration rate, and statin use), number of diseased vessels, atherosclerotic plaque characteristics determined by AI-QCT, and a composite primary outcome of cardiovascular death or myocardial infarction over a median follow-up of 3.3 (interquartile range 2.2-4.4) years. The predictive value of plaque quantification over risk factors was compared in an area under the curve (AUC) analysis. Analysable CCTA data were available from 3711 participants (mean age 64 years, 21% female, 79% multivessel coronary artery disease). Amongst the AI-QCT variables, total plaque volume was most strongly associated with the primary outcome (adjusted hazard ratio 1.56, 95% confidence interval 1.25-1.97 per interquartile range increase [559 mm3]; P = .001). The addition of AI-QCT plaque quantification and characterization to baseline risk factors improved the model's predictive value for the primary outcome at 6 months (AUC 0.688 vs. 0.637; P = .006), at 2 years (AUC 0.660 vs. 0.617; P = .003), and at 4 years of follow-up (AUC 0.654 vs. 0.608; P = .002). The findings were similar for the other reported outcomes. In ISCHEMIA, total plaque volume was associated with cardiovascular death or myocardial infarction. In this highly diseased, high-risk population, enhanced assessment of atherosclerotic burden using AI-QCT-derived measures of plaque volume and composition modestly improved event prediction.

Unbalanced circulating Humanin levels and cardiovascular risk in chronic hemodialysis patients: a pilot, prospective study.

Mortality and cardiovascular (CV) risk prediction in individuals with end-stage kidney disease (ESKD) on chronic hemodialysis (HD) remains challenging due to the multitude of implicated factors. In a multicenter ESKD-HD cohort, we tested the prognostic yield of the assessment ofcirculating Humanin, a small mitochondrial-derived peptide involved in CV protection, on CV events and mortality. We conducted a prospective, observational, pilot study on 94 prevalent HD patients. The prognostic capacity of circulating Humanin levelswas tested on a primary composite (all-cause mortality + non-fatal CV events) and a secondary exploratory endpoint (all-cause mortality alone). Baseline Humanin levelwas comparable in patients reaching the primary or secondary endpoint as compared to others (p = 0.69 and 0.76, respectively). Unadjusted followed by multivariable Cox regression analyses adjusted for age, left ventricular mass index (LVMi), E/e', pulse pressure and diabetes mellitus indicated a non-linear relationship between Humanin levels and the composite outcome with the highest Hazard Ratio (HR) associated with very low (< 450.7pg/mL; HR ranging from 4.25 to 2.49) and very high (> 759.5pg/mL; HR ranging from 5.84 to 4.50) Humanin values. Restricted cubic splines fitting univariate and multivariate Cox regression analyses visually confirmed a curvilinear trend with an increasing risk observed for lower and higher Humanin values around the median, respectively. A similar, u-shaped association was also evidenced with the secondary endpoint. Altered Humanin levels may impart prognostic information in ESKD-HD patients at risk of death or CV events. Future investigations are needed to confirm whether Humanin measurement could improve CV and mortality risk prediction beyond traditional risk models.

Clinicopathological features and outcomes of PLA2R-related membranous nephropathy with renal glycosuria.

Membranous nephropathy (MN) is an immune complex-mediated disease. Massive proteinuria can lead to Fanconi syndrome, clinically manifesting as renal glycosuria. The prevalence and prognosis of M-type phospholipase A2 receptor (PLA2R)-related MN with renal glycosuria remain unknown. Patients diagnosed with PLA2R-related MN with renal glycosuria were reviewed, and the control group comprised patients with MN without renal glycosuria who were randomly selected at a ratio of 1:3. 50 patients diagnosed with PLA2R-related MN with renal glycosuria from January 2015 to January 2020 were included, with a prevalence of 2.3%. Compared with patients without renal glycosuria, those with renal glycosuria exhibited greater proteinuria, lower estimated glomerular filtration rate (eGFR), and higher use of diuretics, anticoagulants, antibiotics, traditional Chinese medicine, and tacrolimus within 3 months prior to renal biopsy (all p<0.05). Histologically, patients with renal glycosuria exhibited more severe pathological stages, acute/chronic tubulointerstitial lesions, and tubulointerstitial inflammation (all p<0.05). Of the 10 patients treated with rituximab (RTX), proteinuria remission was maintained in 6 (60%) patients, and urine glucose remission was achieved in 5 of these 6 patients (83.3%). Multivariate Cox regression analysis showed that renal glycosuria and age >50 years were independent risk factors for end-stage renal disease (ESRD) or a 30% reduction in the eGFR in patients with PLA2R-related MN. PLA2R-related MN patients with renal glycosuria presented with more severe clinicopathological manifestations and worse prognoses. Nephrotoxic drugs should be administered rationally, and RTX should be considered as a promising treatment option.

Computed tomography-based radiomics and clinical-genetic features for brain metastasis prediction in patients with stage III/IV epidermal growth factor receptor-mutant non-small-cell lung cancer.

To evaluate the value of computed tomography (CT)-based radiomics combined with clinical-genetic features in predicting brain metastasis in patients with stage III/IV epidermal growth factor receptor (EGFR)-mutant non-small-cell lung cancer (NSCLC). The study included 147 eligible patients treated at our institution between January 2018 and May 2021. Patients were randomly divided into two cohorts for model training (n = 102) and validation (n = 45). Radiomics features were extracted from the chest CT images before treatment, and a radiomics signature was constructed using the Least Absolute Shrinkage and Selection Operator regression. Kaplan-Meier survival analysis was used to describe the differences in brain metastasis-free survival (BM-FS) risk. A clinical-genetic model was developed using Cox regression analysis. Radiomics, genetic, and combined prediction models were constructed, and their predictive performances were evaluated by the concordance index (C-index). Patients with a low radiomics score had significantly longer BM-FS than those with a high radiomics score in both the training (p < 0.0001) and the validation (p = 0.0016) cohorts. The C-indices of the nomogram, which combined the radiomics signature and N stage, overall stage, third-generation tyrosine kinase inhibitor treatment, and EGFR mutation status, were 0.886 (95% confidence interval [CI] 0.823-0.949) and 0.811 (95% CI 0.719-0.903) in the training and validation cohorts, respectively. The combined model achieved a higher discrimination and clinical utility than the single prediction models. The combined radiomics-genetic model could be used to predict BM-FS in stage III/IV NSCLC patients with EGFR mutations.

PM2.5 constituents associated with mortality and kidney failure in childhood-onset lupus nephritis: A 19-year cohort study

BackgroundChildhood-onset lupus nephritis (cLN) is a severe form of systemic lupus erythematosus (SLE) with high morbidity and mortality. The impact of long-term exposure to fine particulate matter (PM2.5) on adverse outcomes in cLN remains unclear. MethodsWe combined a 19-years cLN cohort from seven provinces in China with high-resolution PM2.5 dataset from 2001 to 2020, investigating the association between long-term exposure to PM2.5 and its constituents (sulfate, nitrate, organic matter, black carbon, ammonium) with the risk of death and kidney failure, analyzed with multiple variables Cox models. We also evaluated the association between 3-year average PM2.5 exposure before study entry and baseline SLE disease activity index (SLEDAI) scores using linear regression models. ResultsEach 10 μg/m3 increase in annual average PM2.5 exposure was associated with an increased risk of death and kidney failure (HR = 1.58, 95 % CI: 1.24–2.02). Black carbon showed the strongest association (HR = 2.14, 95 % CI: 1.47–3.12). Higher 3-year average exposures to PM2.5 and its constituents were significantly associated with higher baseline SLEDAI scores. ConclusionsThese findings highlight the significant role of environmental pollutants in cLN progression and emphasize the need for strategies to mitigate exposure to harmful PM2.5 constituents, particularly in vulnerable pediatric populations.

Incidence and risk factors of SARS-CoV-2 breakthrough infection in the early Omicron variant era among vaccinated and boosted individuals in Chicago.

SARS-CoV-2 vaccines are safe and effective against infection and severe COVID-19 disease worldwide. Certain co-morbid conditions cause immune dysfunction and may reduce immune response to vaccination. In contrast, those with co-morbidities may practice infection prevention strategies. Thus, the real-world clinical impact of co-morbidities on SARS-CoV-2 infection in the recent post-vaccination period is not well established. This study was performed to understand the epidemiology of Omicron breakthrough infection and evaluate associations with number of comorbidities in a vaccinated and boosted population. A retrospective clinical cohort study was performed utilizing the Northwestern Medicine Enterprise Data Warehouse. Our study population was identified as fully vaccinated adults with at least one booster. The primary risk factor of interest was the number of co-morbidities. The primary outcome was the incidence and time to the first positive SARS-CoV-2 molecular test in the Omicron predominant era. Multivariable Cox modeling analyses to determine the hazard of SARS-CoV-2 infection were stratified by calendar time (Period 1: January 1 -June 30, 2022; Period 2: July 1 -December 31, 2022) due to violations in the proportional hazards assumption. In total, 133,191 patients were analyzed. During Period 1, having 3+ comorbidities was associated with increased hazard for breakthrough (HR = 1.16 CI 1.08-1.26). During Period 2 of the study, having 2 comorbidities (HR = 1.45 95% CI 1.26-1.67) and having 3+ comorbidities (HR 1.73, 95% CI 1.51-1.97) were associated with increased hazard for Omicron breakthrough. Older age was associated with decreased hazard in Period 1 of follow-up. Interaction terms for calendar time indicated significant changes in hazard for many factors between the first and second halves of the follow-up period. Omicron breakthrough is common with significantly higher risk for our most vulnerable patients with multiple co-morbidities. Age plays an important role in breakthrough infection with the highest incidence among young adults, which may be due to age-related behavioral factors. These findings reflect real-world differences in immunity and exposure risk behaviors for populations vulnerable to COVID-19.

Survival analysis of unemployment duration: a case study of Vietnam

ABSTRACT How to make own advantages when submitting applications and increase the probability of getting a job early? The target of this study is to analyse the determinants of unemployment duration and the probability of seeking a job after graduation. It is carried out by using survival analysis along with the Cox model and Kaplan–Meier estimator and based on the dataset integrated from survey data and academic data. The empirical results show that taking part-time jobs related to training majors and setting goals as well as planning to go internship early have a positive influence on the ability of students to get a job early. The results also reveal that the mother’s occupation, the type of internment enterprise, the type of work contract, and the refusal of job opportunities offered previously have a negative impact on students’ chances of escaping unemployment. The findings are the basis for students to properly assess their advantages and disadvantages. Thereby, they can determine the goal of a job that suits their capacity and have a reasonable plan combined with their efforts to achieve it. They also support companies to identify groups of potential students and build their suitable evaluation criteria in recruitment.

Association of miR-338-3p with survival outcomes in gastric cancer patients who received peri-operative blood transfusion.

Perioperative blood transfusion (BT) is frequent in the treatment of gastric cancer (GC), but its effects on the prognosis of GC remains controversial. In this study, we aimed to further confirm the relationship of perioperative BT with GC overall survival and to evaluate the predictive value of microRNA-338-3p (miR-338-3p) for the prognosis of GC patients who received perioperative BT. Clinical data and serum samples were collected and analyzed from 246 patients with GC. Five-year follow-up survival information was assessed by Kaplan-Meier survival analysis. miR-338-3p relative expression was assessed by RT-qPCR, and its relationship with the prognosis of GC patients, who received perioperative BT, was evaluated using Kaplan-Meier curves and Cox regression analysis. GC patients received perioperative BT had poor 5year survival than those without BT. In patients received BT, miR-338-3p expression was higher in survival cases than died population and high miR-338-3p was independently associated with better overall survival prognosis. Perioperative BT is related with poor prognosis in GC patients and miR-338-3p may be a prognostic biomarker for GC patients received perioperative BT. BT in perioperative GC patients should be cautious, especially for those with low levels of miR-338-3p.

Mortality in acute ischemic stroke patients with new cancer diagnosed during the index hospitalization versus after discharge

BackgroundEarly diagnosis of previously unknown cancer (i.e., occult cancer) after an acute ischemic stroke (AIS) could result in faster initiation of cancer therapy and potentially improve clinical outcomes. Our study aimed to compare mortality rates between AIS patients with occult cancer diagnosed during the index stroke hospitalization versus those diagnosed after hospital discharge. MethodsAmong consecutive AIS patients treated at our stroke center from 2015 through 2020, we identified new cancer diagnoses made within the year after the AIS. We used multivariable Cox regression analyses to evaluate the association between the timing of occult cancer diagnosis (during the AIS hospitalization versus after discharge) and long-term survival. ResultsOf 3894 AIS patients with available long-term follow-up data, 59 (1.5 %) were diagnosed with a new cancer within one year after index stroke. Of these, 27 (46 %) were diagnosed during the index hospitalization and 32 (54 %) were diagnosed after discharge. During a median follow-up of 406 days (interquartile range, 89–1073), 70 % (n = 19) of patients whose cancer was diagnosed during hospitalization had died, compared to 63 % (n = 20) of patients whose cancer was diagnosed after discharge (p= 0.58). In our main multivariable model, there was no difference in long-term mortality between patient groups (adjusted hazard ratio, 1.16; 95 % confidence interval, 0.53–2.52; p= 0.71). ConclusionsIn this analysis, timing of a new cancer diagnosis after AIS did not seem to influence patients’ long-term survival. Given the fairly small number of included patients with previously occult cancer, larger multicenter studies are needed to confirm our results.

Clinical features and prognostic model for viral encephalitis after allogeneic haematopoietic stem cell transplantation.

The objective of this study was to identify independent prognostic factors of viral encephalitis (VE) after allogeneic haematopoietic stem cell transplantation (allo-HSCT) and establish a prognostic model to identify post-transplant VE patients with a greater likelihood of mortality. Among 5380 patients in our centre from 2014 to 2022, 211 patients who developed VE after allo-HSCT were reviewed in this retrospective study. Prognostic factors were selected, and a prognostic model was constructed using Cox regression analysis. The model was subsequently validated and estimated using the area under the receiver operating characteristic curve (AUC), a calibration plot and decision curve analysis (DCA). Glasgow Coma Scale score <9, lesions >3 lobes on magnetic resonance imaging and severe thrombocytopenia were identified as independent prognostic risk factors for VE patients who underwent allo-HSCT. The prognostic model GTM (GTM is an abbreviation for a model composed of three risk factors: GCS score <9, severe thrombocytopenia [platelet count <20 000 per microliter], and lesions >3 lobes on MRI) was established according to the regression coefficients. The validated internal AUC was 0.862 (95% confidence interval [CI], 0.773-0.950), and the external AUC was 0.815 (95% CI, 0.708-0.922), indicating strong discriminatory ability. Furthermore, we constructed calibration plots that demonstrated good consistency between the predicted outcomes and the observed outcomes. DCA exhibited high accuracy in this system, leading to potential benefits for patients.

Personalized approach to malignant struma ovarii: Insights from a web-based machine learning tool.

Malignant struma ovarii (MSO) is a rare ovarian tumor characterized by mature thyroid tissue. The diverse symptoms and uncommon nature of MSO can create difficulties in its diagnosis and treatment. This study aimed to analyze data and use machine learning methods to understand the prognostic factors and potential management strategies for MSO. In this retrospective cohort, the Surveillance, Epidemiology, and End Results (SEER) database provided the data used for this study's analysis. To identify the prognostic variables, we conducted Cox regression analysis and constructed prognostic models using five machine learning algorithms to predict the 5-year survival. A validation method incorporating the area under the curve of the receiver operating characteristic curve was used to validate the accuracy and reliability of the machine learning models. We also investigated the role of multiple therapeutic options using the Kaplan-Meier survival analysis. The study population comprised 329 patients. Multivariate Cox regression analysis revealed that older age, unmarried status, chemotherapy, and the total number of tumors in patients were poor prognostic factors. Machine learning models revealed that the multilayer perceptron accurately predicted outcomes, followed by the random forest classifier, gradient boosting classifier, K-nearest neighbors, and logistic regression models. The factors that contributed the most were age, marital status, and the total number of tumors in the patients. The present study offers a comprehensive approach for the treatment and prognosis assessment of patients with MSO. The machine learning models we have developed serve as a practical, personalized tool to aid in clinical decision-making processes.

A 18F-FDG PET/CT based radiomics nomogram for predicting disease-free survival in stage II/III colorectal adenocarcinoma.

This study aimed to establish a clinical nomogram model based on a radiomics signatures derived from 18F-fluorodeoxyglucose positron-emission tomography (18F-FDG PET/CT) and clinical parameters to predict disease-free survival (DFS) in patients with stage II/III colorectal adenocarcinoma. Understanding and predicting DFS in these patients is key to optimizing treatment strategies. A retrospective analysis included 332 cases from July 2011 to July 2021 at The Sixth Affiliated Hospital, Sun Yat-sen University, with PET/CT assessing radiomics features and clinicopathological features. Univariate Cox regression, the least absolute shrinkage and selection operator (LASSO) Cox, and multivariable Cox regression identified recurrence-related radiomics features. We used a weighted radiomics score (Rad-score) and independent risk factors to construct a nomogram. Evaluation involved time-dependent receiver operating characteristic (ROC) curves, calibration curves, and decision curve analysis (DCA). The nomogram, incorporating Rad-score, pN, and pT demonstrated robust predictive ability for DFS in stage II/III colorectal adenocarcinoma. Training cohort areas under the curve (AUCs) were 0.78, 0.80, and 0.86 at 1, 2, and 3 years, respectively, and validation cohort AUCs were 0.79, 0.75, and 0.73. DCA and calibration curves affirmed the nomogram's clinical relevance. The 18F-FDG PET/CT based radiomics nomogram, including Rad-score, pN, and pT, effectively predicted tumor recurrence in stage II/III colorectal adenocarcinoma, significantly enhancing prognostic stratification. Our findings highlight the potential of this nomogram as a guide for clinical decision making to improve patient outcomes.

Predictors of improvement in disease activity in childhood and adolescent Crohn's disease: an analysis of age, localization, initial severity and drug therapy - data from the Saxon Registry for Inflammatory Bowel Disease in Children in Germany (2000-2014).

The escalating worldwide prevalence of Crohn's disease (CD) among children and adolescents, coupled with a trend toward earlier onset, presents significant challenges for healthcare systems. Moreover, the chronicity of this condition imposes substantial individual burdens. Consequently, the principal objective of CD treatment revolves around rapid inducing remission. This study scrutinizes the impact of age, gender, initial disease localization, and therapy on the duration to achieve disease activity amelioration. Data from the Saxon Pediatric IBD Registry in Germany were analyzed over a period of 15 years. In addition to descriptive methods, logistic and linear regression analyses were conducted to identify correlations. Furthermore, survival analyses and Cox regressions were utilized to identify factors influencing the time to improvement in disease activity. These effects were expressed as Hazard Ratios (HR) with 95% confidence intervals. Data on the clinical course of 338 children and adolescents with CD were available in the registry. The analyses showed a significant correlation between a young age of onset and the severity of disease activity. It was evident that treatment with anti-TNF (Infliximab) was associated with a more favorable prognosis in terms of the time required for improvement in disease activity. Similarly, favorable outcomes were observed with the combination therapies of infliximab with enteral nutrition therapy and Infliximab with immunosuppressants.Conclusion: Our analysis of data from the Saxon Pediatric IBD Registry revealed that the timeframe for improvement of disease activity in pediatric Crohn's disease is influenced by several factors. Specifically, patient age, treatment modality, and initial site of inflammation were found to be significant factors. The study provides important findings that underline the need for individualized treatment.

Distinct Gene Expression and Immune Features Between Different Neutrophil Extracellular Trap-Related Osteosarcoma Subtypes.

We sought to determine neutrophil extracellular trap (NET)-related genes' potential value in improving the efficacy of diagnosis and identifying novel therapeutic targets for osteosarcoma. Data were obtained from TARGET, GEO, and CCLE database. Differentially expressed genes were identified between the subtypes based on NET-related genes. PPI network was constructed using STRING, following by ClueGO enrichment analysis. Infiltration of immune cells was calculated by ssGSEA. Risk Score model was built by LASSO Cox regression analysis. Western blot and qRT-PCR were applied to validate the expression of genes used in the model. We identified 19 NET-related genes with prognostic potential in osteosarcoma using univariate Cox regression analysis. Patients from TARGET were clustered into two subtypes with distinct prognosis and immune features. 381 DEGs were identified between the two NET subtypes. Risk Score based on BST1, SELPLG, FPR1 and TNFRSF10C was reliable to predict the prognosis of osteosarcoma patients. The four genes expressed significantly lower in osteosarcoma than normal cells. Low Risk Score individuals only existed in C1 subtype with better prognosis. Osteosarcoma were clustered into two subtypes based on NET-related genes. Risk Score model constructed by four NET-related gene was able to independently predict the prognosis of osteosarcoma.

Comparative Safety and Effectiveness of Ustekinumab and Anti-TNF in Elderly Crohn's Disease Patients.

Biologic therapies are associated with increased infection risk among elderly patients with inflammatory bowel disease (IBD). However, there are few data on the safety and effectiveness of ustekinumab compared with anti-tumor necrosis factor (anti-TNF) agents in the elderly. The study sought to compare the safety and effectiveness of ustekinumab and anti-TNF agents in elderly Crohn's disease (CD) patients. Patients ≥60 years of age who commenced ustekinumab or an anti-TNF agent for CD were included in this retrospective multicenter cohort. The primary outcome was incidence of serious infections requiring hospitalization. Effectiveness was assessed by clinical remission, clinical response, and treatment persistence rates at 6 months. We adjusted for confounders using inverse probability of treatment weighting (IPTW) and performed a logistic regression analysis to assess factors associated with serious infections, clinical remission, and treatment persistence. Eighty-three patients commencing ustekinumab and 124 commencing anti-TNF therapy were included. There was no difference in serious infection rates between anti-TNF agents (2.8%) and ustekinumab (3.1%) (P = .924) after propensity adjustment. Clinical remission rates were comparable at 6 months for ustekinumab (55.9%) and anti-TNF agents (52.4%) (P = .762). There was a significant reduction in HBI at 6 months in both groups. Treatment persistence was comparable between ustekinumab (90.6%) and anti-TNF agents (90.0%) at 6 months. Cox regression analysis did not show differences in treatment persistence (hazard ratio, 1.23; 95% confidence interval, 0.57-2.61; P = .594) and serious infection incidence (hazard ratio, 1.38; 95% confidence interval, 0.25-7.57; P = .709) by 6 months. We observed comparable safety and effectiveness for ustekinumab and anti-TNF agents in treating elderly CD patients.

Association of frailty index with all-cause and cardiovascular mortality with different diabetic status: NHANES 1999-2018.

The relationship between frailty and mortality among individuals with varying diabetic statuses represents a burgeoning area of concern and scholarly interest within the medical community. However, there are limited studies that explore the relationship between frailty and mortality, as well as cause-specific mortality among individuals with non-diabetes, prediabetes, and diabetes patients. Hence, this study aims to investigate the relationship between the frailty statues and all-cause mortality, as well as cause-specific mortality in individuals with varying diabetic statuses using the data in the NHANES database. The study utilized data from the National Health and Nutrition Examination Survey (NHANES) 1999-2018, incorporating a final sample size of 57, 098 participants. Both univariable and multivariable-adjusted logistic regression analyses, as well as Cox regression analysis were employed to examine the relationship between frailty index (FI) and mortality. This study, found a significant positive correlation between the frailty and the increased risk of all-cause mortality non-diabetic [OR 4.277, 95%CI (3.982, 4.594), P < 0.001], prediabetic [OR 2.312, 95%CI (2.133, 2.506), P < 0.001], and diabetic patients [OR 3.947, 95%CI (3.378, 4.611), P < 0.001]. This correlation still existed even after adjusting for confounding factors including age, sex, BMI, poverty, fasting insulin, education, smoke, alcohol drink, waist, hypertension, hyperlipidemia, fasting glucose, HbA1c, eGFR, creatinine and total bilirubin. Our result also suggested a significant positive correlation between the frailty index and the increased risk of CVD mortality among non-diabetic [OR 3.095, 95%CI (2.858, 3.352), P < 0.001] and prediabetic [OR 5.985, 95%CI (5.188, 6.904), P < 0.001] individuals. However, in patients with diabetes, the correlation between frailty and CVD mortality lost significance after adjusting for possible confounding factors [OR 1.139, 95%CI (0.794, 1.634), P > 0.05]. A nonlinear relationship has been identified between the FI and all-cause mortality, as well as CVD mortality in non-diabetic and pre-diabetic population. In diabetic patients, there was a significant positive correlation between the frailty and the increased risk of all-cause mortality, but not with CVD mortality. Renal function and liver function might potentially acted as an intermediary factor that elevated the risk of CVD mortality in frail patients with diabetes.

The Association of Preoperative Hip Pain Duration With Delayed Achievement of Clinically Significant Outcomes After Hip Arthroscopic Surgery for Femoroacetabular Impingement Syndrome.

Patients with hip pain ≥2 years before hip arthroscopic surgery for femoroacetabular impingement syndrome (FAIS) have been shown to achieve inferior short-term and midterm outcomes compared with patients with a shorter pain duration, although there is limited literature that has evaluated the time to achieve clinically significant outcomes (CSOs) in this population. To compare the time to achieve CSOs after hip arthroscopic surgery for FAIS in patients with and without prolonged hip pain and to identify independent predictors of the delayed achievement of CSOs. Cohort study; Level of evidence, 3. Patients who underwent primary hip arthroscopic surgery for FAIS between January 2012 and July 2019 with 6-month, 1-year, and 2-year Hip Outcome Score-Activities of Daily Living (HOS-ADL) and Hip Outcome Score-Sports Subscale (HOS-SS) scores were identified. Patients with prolonged hip pain (preoperative duration ≥2 years) were propensity score matched to a control group (preoperative duration <2 years), controlling for age, sex, and body mass index (BMI). The times to achieve the minimal clinically important difference and Patient Acceptable Symptom State were compared between groups using Kaplan-Meier survival analysis. Multivariate Cox regression considering age, sex, BMI, pain duration, activity level, and chondral status was used to identify independent predictors of the delayed achievement of CSOs. A total of 179 patients with prolonged hip pain were matched to 179 control patients (mean pain duration, 60.5 ± 51.2 vs 9.7 ± 5.1 months, respectively; P < .001) of a similar age, sex, and BMI (P≥ .488) with similar baseline HOS-ADL and HOS-SS scores (P≥ .971). The prolonged hip pain group showed delayed achievement of the minimal clinically important difference and Patient Acceptable Symptom State for both the HOS-ADL and HOS-SS on Kaplan-Meier analysis (P≤ .020). On multivariate Cox regression, hip pain duration ≥2 years was shown to be an independent predictor of the delayed achievement of CSOs, with hazard ratios ranging from 1.32 to 1.65 (P≤ .029). Additional independent predictors of the delayed achievement of CSOs included increasing age, increasing BMI, female sex, self-endorsed weekly participation in physical activity, and high-grade chondral defects (hazard ratio range, 1.01-4.89; P≤ .045). Findings from this study demonstrate that preoperative hip pain duration ≥2 years was an independent predictor of the delayed achievement of CSOs after primary hip arthroscopic surgery for FAIS.