Cox Regression Research Articles

Machine learning prediction of hepatic encephalopathy for long-term survival after transjugular intrahepatic portosystemic shunt in acute variceal bleeding

BACKGROUND Transjugular intrahepatic portosystemic shunt (TIPS) is an effective intervention for managing complications of portal hypertension, particularly acute variceal bleeding (AVB). While effective in reducing portal pressure and preventing rebleeding, TIPS is associated with a considerable risk of overt hepatic encephalopathy (OHE), a complication that significantly elevates mortality rates. AIM To develop a machine learning (ML) model to predict OHE occurrence post-TIPS in patients with AVB using a 5-year dataset. METHODS This retrospective single-center study included 218 patients with AVB who underwent TIPS. The dataset was divided into training (70%) and testing (30%) sets. Critical features were identified using embedded methods and recursive feature elimination. Three ML algorithms-random forest, extreme gradient boosting, and logistic regression-were validated via 10-fold cross-validation. SHapley Additive exPlanations analysis was employed to interpret the model’s predictions. Survival analysis was conducted using Kaplan-Meier curves and stepwise Cox regression analysis to compare overall survival (OS) between patients with and without OHE. RESULTS The median OS of the study cohort was 47.83 ± 22.95 months. Among the models evaluated, logistic regression demonstrated the highest performance with an area under the curve (AUC) of 0.825. Key predictors identified were Child-Pugh score, age, and portal vein thrombosis. Kaplan-Meier analysis revealed that patients without OHE had a significantly longer OS (P = 0.005). The 5-year survival rate was 78.4%, with an OHE incidence of 15.1%. Both actual OHE status and predicted OHE value were significant predictors in each Cox model, with model-predicted OHE achieving an AUC of 88.1 in survival prediction. CONCLUSION The ML model accurately predicts post-TIPS OHE and outperforms traditional models, supporting its use in improving outcomes in patients with AVB.

Blood-Based Biomarkers and Risk of Onset of Mild Cognitive Impairment Over the Short and Long Term.

Blood-based biomarkers of amyloid and tau have been shown to predict Alzheimer disease (AD) dementia. Much less is known about their ability to predict risk of mild cognitive impairment (MCI), an earlier disease stage. This study examined whether levels of blood biomarkers of amyloid (Aβ42/Aβ40 ratio), tau (p-tau181), neurodegeneration (NfL), and glial activation and neuroinflammation (glial fibrillary acidic protein [GFAP], YKL40, soluble triggering receptor expressed on myeloid cells 2 [sTREM2]) collected when participants were cognitively normal are associated with the time to onset of MCI. Cognitively unimpaired participants from the longitudinal observational BIOCARD study provided blood plasma at their baseline evaluation ("baseline 1"). A second "baseline" specimen (collected using slightly different procedures) was evaluated for participants who were still cognitively normal approximately 7 years later. The plasma assays were based on the NeuroToolKit (cobas Elecsys assays, Roche Diagnostics). Cox regression models tested the association of biomarker levels with time to MCI symptom onset, separately for both baselines. Participants included 271 individuals at "baseline 1" (mean age = 57.5 years, 60.5% female, including 82 who progressed to MCI/dementia) and 202 individuals at "baseline 2" (mean age = 64.5 years, 62.4% female, including 31 progressors). The mean clinical follow-up was 15.5 years for "baseline 1" and 9.9 years for "baseline 2." For both baselines, lower plasma Aβ42/Aβ40 ratio (both hazard ratios, HRs ≤ 0.69, 95% CIs ≤ 0.55-0.87, p ≤ 0.034), higher GFAP (HRs ≥ 1.83, CIs ≥ 1.28-2.60, p < 0.002), and a higher ratio of p-tau181/(Aβ42/Aβ40) (HRs ≥ 1.64, CIs ≥ 1.25-2.13, p ≤ 0.001) were each associated with an earlier time to MCI symptom onset. For baseline 2, higher p-tau181 (HR = 2.07, CI = 1.12-3.83, p = 0.021) and higher NfL (HR = 1.75, CI = 0.99-3.10, p = 0.05) were also associated with earlier MCI symptom onset for progression within 7 years. When combining biomarkers, neither GFAP nor NFL was associated with MCI symptom onset after accounting for AD biomarker levels (e.g., p-tau181/(Aβ42/Aβ40)), which remained significant. YKL40 and sTREM2 were not associated with MCI onset. Results indicate that during preclinical AD, more abnormal blood biomarker levels of amyloid (Aβ42/Aβ40), p-tau181, neurodegeneration (NfL), and neuroinflammation (GFAP) individually are associated with progression from normal cognition to MCI, but the AD-nonspecific neurodegeneration and inflammation markers were not associated with symptom onset after accounting for amyloid and p-tau levels.

Adjuvant radiation therapy improves outcome of patients with surgical resected adrenocortical carcinoma.

Adrenocortical carcinoma (ACC) is a rare malignancy known for high rates of recurrence and poor prognosis. Previous studies revealed controversial roles of adjuvant radiation therapy (RT) in patient management. This study aimed to investigate the role of adjuvant RT in postoperative ACC patients. Patients with histologically confirmed ACC who underwent surgical resection in the Surveillance, Epidemiology, and End Results (SEER) database between 2004 and 2020 were enrolled. Propensity score matching (PSM) was used to balance baseline characteristics between patients receiving adjuvant RT and patients who did not receive RT. Overall survival (OS) and recurrence-free survival (RFS) was analyzed using the Kaplan-Meir method. Risk factors associated with survival outcome was analyzed by univariate and multivariate Cox regression analyses. Subgroup analyses were stratified by European Network for the Study of Adrenal Tumors (ENSAT) disease stage or chemotherapy. A joint retrospective analysis of stage III patients was performed based on data obtained from Ruijin Hospital and MD Anderson Cancer Center. Among the 700 patients enrolled, 137 patients undergoing postoperative RT were matched with 137 patients who did not receive RT. Overall survival for patients with adjuvant RT was better than patients without RT (log-rank P = 0.015). The 3-year and 5-year OS were 55.2 and 47.1% for patients with RT, vs 42.6 and 34.0% for patients without RT. Multivariate analysis showed adjuvant RT was independently associated with lower mortality (hazard ratio [HR] 0.63, P = 0.007). Subgroup analysis stratified by disease stage demonstrated that adjuvant RT showed the most favorable effect in stage III patients (HR 0.53, P = 0.013). Furthermore, joint analysis of two centers showed a tendency of better OS and local control rate for stage III patients with mitotane plus RT than those with mitotane alone. Our study indicated that adjuvant RT was associated with improved prognosis for ACC patients, especially for patients with ENSAT stage III diseases. Integrating adjuvant RT into standard care of ACC may be considered.

CSPG4 overexpression implicates higher risks of recurrence and tumorigenesis after surgical intervention of vocal fold Leukoplakia.

Vocal fold leukoplakia (VFL), a precancerous lesion of the larynx, is characterized by white plaques on the vocal fold mucous membrane. Currently, there are no reliable biomarkers to predict the recurrence and malignant transformation of VFL. Considering chondroitin sulfate proteoglycan 4 (CSPG4) as a biomarker for malignant tumors such as laryngeal squamous cell carcinoma (LSCC), we conducted this cohort study to evaluate the prognostic influence of CSPG4 expression on VFL patients. This study included 44 patients with surgical intervention of VFL. CSPG4 expression in VFL were observed using immunohistochemistry, and the relationship between the prognosis of VFL patients and CSPG4 expression were investigated using Spearman correlation analysis and multiple Cox regression models. During a median follow-up of 89.3 months, recurrence occurred in 19 postsurgical VFL patients, and malignant transformation occurred in 10 patients. The recurrence and malignant transformation group showed significant differences in the H-SCORE of CSPG4 (P = 0.005 and P = 0.045) compared to the the non-recurrence group and the non-malignant transformation group. And the CSPG4 expression level was positive correlation with recurrence and malignant transformation (0.306 or 0.416, spearman correlation confident). Receiver operating characteristic curve analysis indicated that CSPG4 H-SCORE has predictive value for poor prognosis (areas under the curve, 0.742 and 0.710; cut-off points, 82.5 and 177.5, respectively). Multiple Cox regression analysis revealed a statistically significant effect of lesion size (P = 0.014) and CSPG4 H-SCORE (P = 0.005) on recurrence as well as pathological type (P = 0.001) and CSPG4 H-SCORE stratified by 177.5 (P = 0.039). Our survival data indicated that higher CSPG4 expression was associated with a shorter time of recurrence (P = 0.003) and tumorigenesis (P<0.001). CSPG4 overexpression indicates higher risks and shorter time of postoperative VFL recurrence and tumorigenesis. Detection of CSPG4 expression in VFL may be a novel approach to assess the outcome of VFL patients.

Extracellular vesicles from pancreatic cancer and its tumour microenvironment promote increased Schwann cell migration.

Pancreatic ductal adenocarcinoma (PDAC) exhibits a high frequency of neural invasion (NI). Schwann cells (SCs) have been shown to be reprogrammed to facilitate cancer cell migration and invasion into nerves. Since extracellular vesicles (EVs) affect the tumour microenvironment and promote metastasis, the present study analysed the involvement of EVs from pancreatic cancer cells and their microenvironment in altering SC phenotype as part of the early events in the process of NI. EVs were isolated from human/murine PDAC cells, pancreatic stellate cells (PSCs), human tissues and plasma to perform a novel 3D migration assay, qRT-PCR and western blot. Kaplan-Meier and Cox regression analyses were employed to evaluate the clinical potential of plasma EV-derived candidate from 165 PDAC patients. The EVs from PDAC cells, PSCs derived from human tumour tissues, other cell types in the tumour microenvironment from tumour tissues and circulating plasma act as drivers of a pro-migratory phenotype of SCs by inducing dedifferentiation in SCs. Notably, p75NTR expression was upregulated in the plasma-derived EVs from patients with NI (Pn1) relative to those without NI (Pn0). High expression of plasma-derived EV p75NTR correlated with reduced overall survival and was identified as an independent prognostic factor. These findings suggest that EV-mediated SC migration underlies the interactions contributing to PDAC-associated NI with implications for improved outcome and therapeutic strategy.

Clinical characteristics and prognosis of ovarian juvenile granulosa cell tumors

Objective: To analyze the clinical characteristics, treatments, and prognosis of patients with ovarian juvenile granulosa cell tumor (JGCT). Methods: Clinical and pathological data, and follow-up information of 34 patients diagnosed with JGCT from 2000 to 2021 were collected from the surveillance, epidemiology, and end results (SEER) database. A retrospective analysis was conducted to summarize the patients' clinical and pathological characteristics, treatments, and prognosis. Propensity score matching (PSM) was used to match the JGCT cases with adult granulosa cell tumor (AGCT) cases in SEER database. A total of 96 patients with ovarian granulosa cell tumor (OGCT), including 32 cases of JGCT and 64 cases of AGCT, were enrolled in a matched cohort analysis. Univariate and multivariate Cox regression analysis were performed on the matched cohort to explore the risk factors for overall survival. Kaplan-Meier curves and the log-rank test were used to compare the survival outcomes between JGCT and AGCT. Results: (1) The median age at diagnosis for the 34 JGCT patients was 19.5 years (ranged: 1-48 years), with 3 patients aged ≤10 years, 16 patients aged 11-20 years, 11 patients aged 21-30 years, and 4 patients aged >30 years. Tumors originated unilaterally in 33 patients, with only 1 case originating bilaterally. The maximum tumor diameter was recorded in 26 patients, with a median size of 12.4 cm (ranged: 3.5-40.0 cm). According to the 2014 International Federation of Gynecology and Obstetrics (FIGO) staging system, 19 patients were diagnosed with stage Ⅰ (including 10 cases with stage Ⅰa and 9 cases with stage Ⅰc), 4 patients with stage Ⅱ, 8 patients with stage Ⅲ, and 3 patients with stage Ⅳ. Two patients did not undergo surgery for the resection of lesions. Stage Ⅰ patients (15/19) underwent fertility-sparing surgery, while stage Ⅱ-Ⅲ patients underwent either fertility-sparing surgery or cytoreductive surgery (6 cases each). Stage Ⅳ patients underwent cytoreductive surgery (2 cases). Lymph node dissection was performed in 10 patients, among which only 1 patient with positive lymph nodes metastasis. None of the 34 patients received radiotherapy, while 18 patients received adjuvant chemotherapy (included neoadjuvant chemotherapy and postoperative adjuvant chemotherapy). The proportion of stage Ⅰ patients receiving adjuvant chemotherapy was relatively low, with only 4 out of 19 patients (including 2 out of 10 cases for stage Ⅰa and 2 out of 9 cases for stage Ⅰc). The proportions of patients receiving adjuvant chemotherapy for stages Ⅱ, Ⅲ and Ⅳ were 3 out of 4 cases, 8 out of 8 cases, and 3 out of 3 cases, respectively. The follow-up ended in December 2021, with 20 patients alive and 14 dead. The survival rate for ovarian JGCT patients was 59% (20/34). Among them, the survival rate for stage Ⅰ patients was 16/19, while for stage Ⅱ-Ⅳ patients, it was 4/15; there was a statistically significant difference (P=0.002). Among stage Ⅱ-Ⅲ patients, the survival rate at the end of follow-up was 1/6 for those who underwent fertility-sparing surgery, compared to 3/6 for those who underwent cytoreductive surgery (P=0.546). (2) For the 96 OGCT patients after matching using the PSM method, 64 ovarian AGCT patients had 5 deaths and 59 survivors during the follow-up period, the survival rate was 92% (59/64) at the end of follow-up. In contrast, among the 32 ovarian JGCT patients, 13 died and 19 survived, resulting in a survival rate of 59% (19/32) at the end of follow-up, which was statistically significant difference for the AGCT group (P<0.001). Univariate Cox analysis revealed that histology, extent of surgery, chemotherapy, postoperative tumor residual status, and stage all significantly affected the survival outcomes of OGCT patients (all P<0.05). Multivariate Cox analysis revealed that variables with significant statistical differences were histology and stage. The median survival time for JGCT patients was 126 months, while AGCT patients median survival time was not reached with a statistically significant between the two groups (P<0.001). Conclusions: Ovarian JGCT predominantly occur in adolescents and young women. Lymph node metastasis is relatively rare, and treatment primarily involves surgery and adjuvant chemotherapy. Most ovarian JGCT patients are diagnosed at stage Ⅰ, with a favorable prognosis. Fertility-preserving surgery is recommended, involving salpingo-oophorectomy on the affected side plus comprehensive staging surgery, or a second surgery to achieve comprehensive staging. For stage Ⅱ-Ⅳ ovarian JGCT patients, the prognosis is relatively poor, and fertility-preserving surgery should be considered with caution. The prognosis of ovarian JGCT patients is worse than that of ovarian AGCT patients.

Computed tomography-based nomogram for estimating progression-free survival probability in bladder cancer patients undergoing partial cystectomy.

To establish a prognostic model to estimate progression-free survival (PFS) probability in bladder cancer (BCa) patients undergoing partial cystectomy. Consecutive patients who underwent partial cystectomy between August 2012 and April 2021 were enrolled. The primary endpoint was PFS during the follow-up. The following features were assessed: tumor location, amount, size, tortuous blood vessels around or within the lesions, perivesical fat stranding, stalk, computed tomography (CT) enhancement, calcification, cystic degeneration, CT reported lymph nodes status, and presence of hydronephrosis. Univariate Cox regression and LASSO regression, followed by backward stepwise multivariable Cox, were used to construct the nomogram. A total of 106 patients were enrolled. Gender, histology, tortuous blood vessels, and perivesical fat stranding were used to fit the nomogram. The overall Harrell's concordance index (C-index) was 0.752. The area under the receiver operator characteristic curves (AUC) at 1-year, 2-year and 3-year were 0.733, 0.789 and 0.833, respectively. The calibration curves showed remarkable consistency. A nomogram model constructed based on the CT features and clinical risk factors is potentially feasible for predicting the PFS within 3years after PC for BCa, which can assist in the choice of treatment and follow-up scheduling.

Intracellular dark endothelial spots detected using specular microscopy are associated with graft failure after Descemet's membrane endothelial keratoplasty.

To investigate the correlation between intracellular dark endothelial spots (IDESs) detected by specular microscopy and the incidence of graft failure after Descemet's membrane endothelial keratoplasty (DMEK). We reviewed 100 consecutive DMEK patients performed by a single surgeon at two centres between January 2015 and July 2022. Central corneal thickness was evaluated using anterior segment optical coherence tomography (SS-1000; Tomey, Aichi, Japan), and endothelial cell density was measured using specular microscopy. Kaplan-Meier estimates and Cox regression models were used to evaluate graft failure and associated risk factors. Of the 97 eyes included, 9 experienced graft failure within the follow-up period (52.9 ± 23.9 months). IDES presence significantly correlated with decreased endothelial cell density and higher graft failure rates (hazard ratio = 4.68, 95% confidence interval = [0.96, 22.7], P = 0.034). IDESs represent a significant risk factor for graft failure post-DMEK. Careful postoperative management is imperative to minimise this risk.

Predictive value of insulin resistance metabolic score for cardiovascular disease in Chinese arthritis patients: a prospective cohort study.

Although patients with arthritis have significantly increased cardiovascular disease (CVD) risk, effective prediction tools remain limited. This study aimed to evaluate the predictive value of the Metabolic Score for Insulin Resistance (METS-IR) for CVD events among Chinese patients with arthritis. Using data from the China Health and Retirement Longitudinal Study (CHARLS), we conducted a 7-year prospective cohort study (2011-2018) involving 1,059 patients with arthritis. The primary exposure was baseline METS-IR, and the primary outcome was incident CVD. Multivariate Cox regression models were used to analyze the association between METS-IR and CVD risk, adjusting for demographic characteristics and lifestyle factors. After adjusting for confounding factors, each quartile increase in METS-IR was associated with a 36% increased risk of CVD (HR = 1.36,95%CI : 1.14-1.61, p< 0.001). Compared with the lowest quartile, the highest quartile showed a 63% increased risk (HR = 1.63,95%CI : 1.12-2.37, p< 0.05), demonstrating a significant dose-response relationship (p for trend < 0.05). METS-IR serves as an effective tool for predicting CVD risk among Chinese patients with arthritis, providing new strategies for early risk identification and prevention.

Development and validation of a prediction model for estimating patency rates after treatment of haemodialysis access dysfunction.

This study aims to develop a risk assessment model for predicting haemodialysis access dysfunction and to construct a nomogram. The clinical data of patients with haemodialysis access dysfunction treated at our hospital from October 2020 to January 2024 were retrospectively analysed. The least absolute shrinkage and selection operator regression method was used to filter variables and select predictors, while Cox regression was applied to filter variables and construct a nomogram. The discriminatory ability of the model was determined by calculating the area under the curve (AUC). Calibration was evaluated using bootstrap internal validation and the Hosmer-Lemeshow test. The clinical utility and applicability of the model were assessed through decision curve analysis (DCA) and the clinical impact curve (CIC). Subgroup analysis of risk factors for haemodialysis access dysfunction was performed using Kaplan-Meier survival curves. The study included 423 patients, and seven variables were used to construct the risk prediction model and nomogram for haemodialysis access dysfunction. The C-index of the prediction model was 0.783, and the time-dependent AUC (>0.8) at 6, 12, 18 and 24 months post-surgery indicated strong discriminatory ability. The calibration curve and Hosmer-Lemeshow test demonstrated good agreement between the prediction of the nomogram and the observed values. The DCA and CIC curves further confirmed the clinical practicability of the model. A risk assessment model and nomogram for haemodialysis access dysfunction based on seven variables were successfully constructed. This model demonstrates good discrimination and calibration, offering valuable guidance for clinical decision-making and significant clinical utility.

Metabolic profiling of meningioma reveals novel subgroup-specific biologic insights and outcome dependencies.

Our group and others have recently identified four molecular groups of meningioma, with unique underlying biology and outcomes. The relevance of group-specific metabolite profiles (particularly among hypermetabolic tumours), has not been explored. We performed untargeted metabolic profiling of meningiomas representing each molecular group and WHO grade. Prognostic biochemicals were identified using Cox regression and their biological importance was explored using RNA and protein-based pathway analyses. Validation was performed using targeted high performance liquid chromatography-mass spectrometry (HPLC-MS/MS). Global metabolic profiling identified 560 unique biochemicals. We identified a 21-metabolite outcome signatures which is strongly predictive of outcome after adjusting for WHO grade, extent of resection, and receipt of adjuvant radiotherapy (HR 326.49, 95%CI 16.72-6375.48, p < 0.0001). The abundance of N6-trimethyllysine was associated with earlier time to recurrence on our whole cohort (log-rank p = 0.009) and within hypermetabolic and WHO grade 2 tumours specifically; this was validated using targeted HPLC-MS/MS on two cohorts. Consensus RNA and protein expression analysis demonstrated as association between N6-trimethyllysine abundance and activation of oxidative phosphorylation pathways, which portended worse outcomes in the hypermetabolic subgroup but, interestingly, better outcomes in the proliferative subgroup. By contrast, upregulated pyruvate and lactate transporters were associated with worse outcomes in proliferative meningiomas specifically. This is the first study to demonstrate a subgroup-specific prognostic role of N6-trimethyllysine in hypermetabolic meningiomas, offering increasingly granular outcome predictions using a widely accessible technique (HPLC-MS/MS). We also suggest fundamental differences in preferred energy utilization between and a potential need for subgroup-specific therapies.

Associations of Serum Urate and Cardiovascular Events in a ClinicalTrialofInterleukin-1β Blockade.

Serum urate (SU) associates with cardiovascular (CV) events, mortality, and gout. The purpose of this study was to assess whether SU predicts CV risk in a trial of interleukin (IL)-1β inhibition with canakinumab, and whether IL-1β blockade, kidney function, or gout alter these associations. This study is a subanalysis of the Canakinumab Antiinflammatory Thrombosis Outcome Study (CANTOS), which randomized 10,061 patients with prior myocardial infarction and elevated high-sensitivity C-reactive protein to 3doses of canakinumab or placebo. SU was measured at baseline. Cox proportional hazards models compared major adverse cardiovascular events (MACE), CV death, and all-cause mortality among those with SU≤6.8mg/dL (normal), 6.8 to 9.0mg/dL (elevated), and≥9.0mg/dL (markedly elevated). Cox regressions were repeated within subgroups, including canakinumab vs placebo, estimated glomerular filtration rate≥60 vs<60mL/min, and gout vs nogout. Markedly elevated SU associated with MACE (HR: 1.66 [95% CI: 1.38-1.99]; P<0.0001), CV death (HR: 2.52 [95% CI: 1.98-3.21]; P<0.0001), and all-cause mortality (HR: 2.43 [95% CI: 2.01-2.94]; P<0.0001) compared to normal SU. After multivariable adjustment for a minimal set of potential confounders, SU independently predicted all 3endpoints. Associations were unchanged after IL-1β blockade with canakinumab. For normal estimated glomerular filtration rate, SU associated with CV and all-cause mortality, but not MACE. Participants with gout had higher event rates independent of SU. In over 10,000 patients with coronary artery disease, individuals with markedly elevated SU have elevated CV risk despite aggressive treatment. IL-1β blockade did not modify these associations. Baseline kidney function and monosodium urate deposition may function as effect modifiers.

Machine Learning to Predict Mortality in Older Patients With Cancer: Development and External Validation of the Geriatric Cancer Scoring System Using Two Large French Cohorts.

Establishing an accurate prognosis remains challenging in older patients with cancer because of the population's heterogeneity and the current predictive models' reduced ability to capture the complex interactions between oncologic and geriatric predictors. We aim to develop and externally validate a new predictive score (the Geriatric Cancer Scoring System [GCSS]) to refine individualized prognosis for older patients with cancer during the first year after a geriatric assessment (GA). Data were collected from two French prospective multicenter cohorts of patients with cancer 70 years and older, referred for GA: ELCAPA (training set January 2007-March 2016) and ONCODAGE (validation set August 2008-March 2010). Candidate predictors included baseline oncologic and geriatric factors and routine biomarkers. We built predictive models using Cox regression, single decision tree (DT), and random survival forest (RSF) methods, comparing their predictive performance for 3-, 6-, and 12-month mortalities by computing time-dependent area under the receiver operator curve (tAUC). A total of 2,012 and 1,397 patients were included in the training and validation set, respectively (mean age: 81 ± 6 years/78 ± 5 years; women: 47%/70%; metastatic cancer: 50%/34%; 12-month mortality: 43%/16%). Tumor site/metastatic status, cancer treatment, weight loss, ≥five prescription drugs, impaired functional status and mobility, abnormal G-8 score, low creatinine clearance, and elevated C-reactive protein (CRP)/albumin were identified as relevant predictors in the Cox model. DT and RSF identified more complex combinations of features, with G-8 score, tumor site/metastatic status, and CRP/albumin ratio contributing most to the predictions. The RSF approach gave the highest tAUC (12 months: 0.87 [RSF], 0.82 [Cox], 0.82 [DT]) and was retained as the final model. The GCSS on the basis of a machine learning approach applied to two large French cohorts gave an accurate externally validated mortality prediction. The GCSS might improve decision making and counseling in older patients with cancer referred for pretherapeutic GA. GCSS's generalizability must now be confirmed in an international setting.

Comparison of the efficacy between Super-Path and Watson-Jones approaches in the management of early femoral head necrosis.

This study compares and investigates the efficacy of 2 different surgical methods for early stage femoral head necrosis and analyze the factors affecting surgical outcomes and long-term femoral head survival. A retrospective analysis was conducted on the clinical data of 48 patients (52 hips) with femoral head necrosis who underwent either the Super-Path or Watson-Jones approach from January 1, 2016, to January 1, 2024. Harris scores at multiple time points before and after surgery were compared using repeated-measures analysis of variance (ANOVA), and a COX proportional hazards model was used to analyze risk factors. The baseline data of the 2 groups were comparable (P > .05). There was no significant difference in preoperative Harris scores or scores at 3 and 12 months postoperatively (t = 0, P = 1; t = 0.719, 0.476; P = .716, .477). However, a significant difference was found at 36 months postoperatively (t = 2.118, P = .04). The preoperative stage of femoral head necrosis, patient gender, and surgical method were significant risk factors. The survival curves showed similar survival rates for the first 10 months, with no significant difference at 36 months (P = .5139). Both surgical approaches were effective in improving short-term hip function but did not show sustained long-term improvement. The Super-Path approach demonstrated better long-term outcomes compared to the Watson-Jones approach, influenced by surgical and temporal factors and preoperative staging. The COX model indicated that preoperative staging, female gender, and the surgical procedure were positively correlated with the risk of femoral head necrosis.

Association of Geriatric Nutritional Risk Index Scores with Outcomes in Patients Undergoing Maintenance Hemodialysis.

Aims/Background The Geriatric Nutritional Risk Index (GNRI) is an effective tool for identifying malnutrition, and helps monitor the prognosis of patients undergoing maintenance hemodialysis. However, the association between the GNRI and cardiovascular or all-cause mortality in hemodialysis patients remains unclear. Therefore, this study investigated the correlation of the GNRI with all-cause and cardiovascular mortality in patients undergoing maintenance hemodialysis. Methods This study included 402 incident hemodialysis patients. Based on the first-dialysis GNRI quartile, the patients were divided into four groups: N1 (GNRI ≤85.04), N2 (GNRI 85.05-91.04), N3 (91.05-96.49), N4 (GNRI ≥96.5) groups. The risk of all-cause and cardiovascular mortality among the different GNRI groups was compared using the Kaplan-Meier survival curve analysis through log-rank tests. Furthermore, Cox regression analysis was used to assess the association between the GNRI groups and all-cause mortality. Additionally, the predictive capability of the GNRI groups on the prognosis was evaluated by employing receiver operating characteristic (ROC) curve analysis. Results Patients in the N1 group exhibited a significantly higher risk of all-cause mortality (p < 0.001) and cardiovascular mortality (p = 0.004) compared to the other groups. ROC curve analysis revealed that GNRI, age, and serum creatinine had moderate predictive value for mortality, with GNRI indicating an area under the curve (AUC) of 0.605 for all-cause mortality and 0.565 for cardiovascular mortality. Moreover, the N2 and N3 groups had a significantly reduced risk of cardiovascular mortality compared to the N1 group. Conclusion A lower GNRI is closely associated with a higher risk of all-cause and cardiovascular mortality in hemodialysis patients.

Proton pump inhibitors and all-cause mortality risk among cancer patients

BACKGROUND Proton pump inhibitors (PPIs) are widely used, including among cancer patients, to manage gastroesophageal reflux and other gastric acid-related disorders. Recent evidence suggests associations between long-term PPI use and higher risks for various adverse health outcomes, including greater mortality. AIM To investigate the association between PPI use and all-cause mortality among cancer patients by a comprehensive analysis after adjustment for various confounders and a robust methodological approach to minimize bias. METHODS This retrospective cohort study used data from the TriNetX research network, with electronic health records from multiple healthcare organizations. The study employed a new-user, active comparator design, which compared newly treated PPI users with non-users and newly treated histamine2 receptor antagonists (H2RA) users among adult cancer patients. Newly prescribed PPIs (esomeprazole, lansoprazole, omeprazole, pantoprazole, or rabeprazole) users were compared to non-users or newly prescribed H2RAs (cimetidine, famotidine, nizatidine, or ranitidine) users. The primary outcome was all-cause mortality. Each patient in the main group was matched to a patient in the control group using 1:1 propensity score matching to reduce confounding effects. Multivariable Cox regression models were used to estimate hazard ratios (HRs) and 95% confidence interval (CI). RESULTS During the follow-up period (median 5.4 ± 1.8 years for PPI users and 6.5 ± 1.0 years for non-users), PPI users demonstrated a higher all-cause mortality rate than non-users after 1 year, 2 years, and at the end of follow up (HRs: 2.34-2.72). Compared with H2RA users, PPI users demonstrated a higher rate of all-cause mortality HR: 1.51 (95%CI: 1.41-1.69). Similar results were observed across sensitivity analyses by excluding deaths from the first 9 months and 1-year post-exposure, confirming the robustness of these findings. In a sensitivity analysis, we analyzed all-cause mortality outcomes between former PPI users and individuals who have never used PPIs, providing insights into the long-term effects of past PPI use. In addition, at 1-year follow-up, the analysis revealed a significant difference in mortality rates between former PPI users and non-users (HR: 1.84; 95%CI: 1.82-1.96). CONCLUSION PPI use among cancer patients was associated with a higher risk of all-cause mortality compared to non-users or H2RA users. These findings emphasize the need for cautious use of PPIs in cancer patients and suggest that alternative treatments should be considered when clinically feasible. However, further studies are needed to corroborate our findings, given the significant adverse outcomes in cancer patients.

Prognostic value of coronary plaque composition in symptomatic patients with obstructive coronary artery disease.

To determine whether plaque composition analysis defined by cardiac CT can provide incremental prognostic value above coronary artery disease (CAD) burden markers in symptomatic patients with obstructive CAD. Between 2009 and 2019, a multicentric registry included all consecutive symptomatic patients with obstructive CAD (at least one ≥ 50% stenosis on CCTA) and was followed for major adverse cardiovascular (MACE) defined by cardiovascular death or nonfatal myocardial infarction. Each coronary segment was scored visually for both the degree of stenosis and composition of plaque, which were classified as non-calcified, mixed, or calcified. To assess the prognostic value of each CCTA findings, different multivariable Cox regression models were used: model 1: clinical (traditional risk factors); model 2: model 1 + CAD burden (number of proximal segments with stenosis ≥ 50% + number of vessels with obstructive CAD); and model 3: model 2 + plaques feature (number of segments with non-calcified plaque). Of 2312 patients (mean age 70 ± 12 years, 46% men), 319 experienced a MACE (13.8%) (median follow-up: 6.7 years (5.9-9.1)). The number of proximal segments with ≥ 50% stenosis, the number of vessels with obstructive CAD, and the number of segments with non-calcified plaque were all independently associated with MACEs (all p < 0.001). The addition of plaque composition analysis (model 3) showed the best improvement in model discrimination and reclassification (C-statistic improvement = 0.03; net reclassification improvement = 28.6%; integrative discrimination index = 5.4%, all p < 0.001). In this population, the analysis of coronary plaque composition had an incremental prognostic value to predict MACEs above a model combining traditional risk factors and CAD burden. Question Several coronary computed tomography angiography (CCTA) studies have shown the potential interest of plaque composition analysis, which can be further evaluated. Findings In symptomatic patients with obstructive coronary artery disease (CAD), plaque composition analysis had an incremental prognostic value above a model combining traditional risk factors and CAD burden. Clinical relevance In symptomatic patients with obstructive CAD, plaque composition analysis using CCTA has a strong incremental prognostic value above a model combining traditional risk factors and CAD burden, thus translating into a more accurate long-term major adverse cardiovascular event prediction.

Association between body mass index, obesity, and vulvar cancer recurrence.

The objective of this paper is to study the association between obesity and tumor recurrence in patients with vulvar cancer. This is a retrospective study including vulvar cancer patients from 2003 to 2022. Our primary outcome was progression-free survival (PFS) stratified by status of obesity, defined as body mass index (BMI) >30.0 kg/m2. Overall, 48 patients were included in the study, with 32 (66.7%) diagnosed at early stages (I-II). The median BMI was 28.0 kg/m2 [interquartile range 24.9-32.3 kg/m2]. There were 13 obese patients (27%), and the median follow-up time was 55 months [interquartile range 14-102]. Most patients (80%) were HPV-independent of human papilloma virus. Surgical intervention was the primary treatment modality for 88% (n = 42) of the cohort, and 26 patients (54%) received adjuvant chemoradiation. Disease recurrence was identified in 28 patients (58%). The median PFS was 68 months, and the median overall survival was 109 months. There was no difference in the median PFS between obese patients and non-obese patients (P = 0.370). In a Cox regression analysis, after adjusting for patient age, margin-free distance, and stage of disease, BMI was not associated with PFS hazard ratio 1.06 (0.99-1.12). Obesity is not associated with PFS in patients with vulvar cancer, and BMI might not be considered a risk factor for recurrence.

Impact of preoperative frailty on outcomes in patients subjected to emergency laparotomy: a prospective study.

Emergency laparotomy (EL) is a high-risk procedure, especially in frail patients. This study investigates the prevalence of frailty in referral facilities, evaluates the impact of frailty on postoperative morbidity and mortality, and assesses the long-term effect of EL on patients' functional status. This prospective multicentre cohort study included patients aged 50 years and older who underwent EL. Frailty was assessed using the Clinical Frailty Scale (CFS). The primary outcome measure was the prevalence of frailty and its impact on the 180-day mortality rate after EL. Secondary outcomes were 30- and 90-day mortality, complications requiring invasive procedures, length of hospital stay (LOS), and changes in CFS and in living arrangement at six months post-operation. The study enrolled 251 patients with a median age of 73 years. Frailty was prevalent, with 57.8% of patients classified as frail (CFS 5-9). In Cox regression analysis, the hazard ratios of 180-day mortality with 95% confidence intervals were 2.4 (0.8-7.1) for CFS 4, 7.5 (2.8-20.0) for CFS 5, 14.4 (5.5-37.8) for CFS 6-8, and 28.7 (9.7-84.6) for CFS 9, compared to non-frail patients. Increasing frailty was also associated with higher 30 and 90- day mortality, increased risk of complications, and prolonged LOS. Additionally, at six months post-EL, patients experienced a further decline in functional status compared to their preoperative state. The 180-day mortality after EL is significantly higher for patients on higher levels of frailty. Likewise, the preoperative frailty has a significant negative impact on postoperative outcomes both short- and long-term.

Evaluation the role of the nephrology team in the specific vascular access outpatient clinic. What can we contribute new?

The key points of a monographic vascular access (VA) consultation are an adequate preoperative assessment, as well as a correct management and optimization of waiting lists. Our main objective of present study was to evaluate the degree of exploratory-dependent concordance in outpatient clinics regarding implanted VA, between nephrology and vascular surgery. We analyzed VA created or surgically repaired between 2021 and 2022. We compared the differences in the preoperative variables between the groups in which the assessments between the two teams were coincident and non-coincident, and the primary (PP) and secondary (PS) patencies during the follow-up period (Kapplan-Meier curves and Log-rank test, and Cox regression analysis). Significant P ≤ 0.05. A total of 605 VA creations or repairs were analyzed: 74 ligations (12.2%), 207 distal arterio-venous fistulaes (AVF) (34.3%), 237 proximal AVF (39.2%), 35 repairs (5.7%), 41 grafts (6.7%) and 11 others (1.9%). After an average waiting list time of 16.5 ± 11.6 days, excluding ligations, adequate 1-month maturation was observed in 87.6% of cases. A total of 158 endovascular procedures and 17 surgical repairs were performed during postoperative follow-up. Primary (PP) and secondary (PS) patencies at 6, 12 and 24 months were PP: 76.2%, 64.9%, 57.5% and PS: 86.4%, 81.2%, 74.7%, respectively. Of the total number of procedures, nephrology obtained an adequate degree of agreement in 93.6% of the cases (kappa index: 0.886). The preoperative factors associated with greater discrepancies in assessments were age (P = 0.022) and arterial diameter (P = 0.032). The subgroup of non-matched assessments between nephrology and vascular surgery (39 cases) presented a similar PP (at 2 years: 59.2% vs 41.3%, P = 0.099) but worse PS (at 2 years: 76.6% vs 55.4%, P = 0.005). No significant observer-dependent differences (nephrologist vs. vascular surgeon) were observed in decision-making regarding the surgical procedure to be performed (93.6% agreement), and discordant cases presented worse secondary patency. After specific training, the nephrology coordination team can make a proper optimisation of social and health resources by reserving referrals to vascular surgery for those cases of greater complexity.