Kaplan-Meier Research Articles

Time to death and its determinant factors of stroke patients at Gambella General Hospital, Gambella, Ethiopia

Background and purposeA stroke or a cerebrovascular accident is a common cause of death and a leading cause of long-term, severe disability in both developed and developing countries. The most recent global burden of disease report states that there were 11.9 million new cases of stroke worldwide; stroke accounts for nearly 1 in 8 deaths globally (12%, 6.5 million deaths) and claims a life every 5 s, making it the second most common cause of death worldwide. The goal of the study was to identify the most important factors influencing stroke patients' time to death at Gambella General Hospital.MethodsData was gathered from patient files in a hospital using a retrospective study methodology, spanning the period from September 2018 to September 2020. R 3.4.0 statistical software and STATA version 14.2 were used for data entry and analysis. The survival time was compared using the log-rank tests and the Kaplan–Meier survival curve. The fitness of the Cox proportional hazard model was examined.ResultsThe final model that was fitted was the log-logistic AFT model. A statistically significant correlation was defined as having a p value of less than 0.05 and the accelerated factor (γ) with its 95% confidence interval was employed. Eight days was the total median death time (95% CI 6–10). Significant predictors for shortened mortality time were age (γ = 0.94; 95% CI (0.0.920–0.980), hypertension (γ = 0.63; 95% CI (0.605–0.660), and baseline complications (γ = 0.24; 95% CI (0.223–0.256).ConclusionsThe shortened timing of death was significantly predicted by age, hypertension, and baseline complications. In light of the study's findings, health administrators and caregivers should work to improve society's overall health.

Prognostic model for predicting recurrence in hepatocellular carcinoma patients with high systemic immune-inflammation index based on machine learning in a multicenter study

IntroductionThis study aims to use machine learning to conduct in-depth analysis of key factors affecting the recurrence of HCC patients with high preoperative systemic immune-inflammation index (SII) levels after receiving ablation treatment, and based on this, construct a nomogram model for predicting recurrence-free survival (RFS) of patients.MethodsThis study included clinical data of 505 HCC patients who underwent ablation therapy at Beijing You’an Hospital from January 2014 to January 2020, and accepted 65 HCC patients with high SII levels from Beijing Ditan Hospital as an external validation cohort. 505 patients from Beijing You’an Hospital were divided into low SII and high SII groups based on the optimal cutoff value of SII scores. The high SII group was further randomly divided into training and validation cohorts in a 7:3 ratio. eXtreme Gradient Boosting (XGBoost), random survival forest (RSF), and multivariate Cox regression analysis, were used to explore the factors affecting the post-ablation RFS of HCC patients. Based on the identified key factors, a nomogram model were developed to predict RFS in HCC patients, and their performance were evaluated using the concordance index (C index), receiver operating characteristic curve (ROC), calibration curve, and decision curve analysis (DCA). The optimal cutoff value for nomogram scores was used to divide patients into low- and high-risk groups, and the effectiveness of the model in risk stratification was evaluated using Kaplan-Meier (KM) survival curves.ResultsThis study confirmed that age, BCLC stage, tumor number, and GGT level were independent risk factors affecting RFS in HCC patients. Based on the selected risk factors, an RFS nomogram was successfully constructed. The C-index, ROC curve, calibration curve, and DCA curve each demonstrated the discrimination, accuracy, and decision-making utility of the nomogram, indicating that it has good predictive performance. KM curve revealed the nomogram could significantly differentiate patient populations with different recurrence risk.ConclusionWe developed a reliable nomogram that can accurately predict the 1-, 3-, and 5-year RFS for HCC patients with high SII levels following ablation therapy.

Bacterial infections and outcomes of inpatients with COVID-19 in the intensive care unit during the delta-dominant phase: the worst wave of pandemic in Iran

BackgroundEpidemiological data regarding the prevalence of bacterial multidrug-resistant (MDR) Gram-negative infections in patients with COVID-19 in Iran are still ambiguous. Thus, in this study we have investigated the epidemiology, risk factors for death, and clinical outcomes of bacterial infections among patients with COVID-19 in the intensive care unit (ICU).MethodThis retrospective cohort study included patients with COVID-19 hospitalized in the ICU of a university hospital in Iran between June 2021 and December 2021. We evaluated the epidemiological, clinical, and microbiological features, outcomes and risk factors associated with death among all COVID-19 patients. Data and outcomes of these patients with or without bacterial infections were compared. Kaplan–Meier plot was used for survival analyses.ResultsIn total, 505 COVID-19 patients were included. The mean age of the patients was 52.7 ± 17.6 years and 289 (57.2%) were female. The prevalence of bacterial infections among hospitalized patients was 14.9%, most of them being hospital-acquired superinfections (13.3%). MDR Klebsiella pneumoniae and Staphylococcus aureus were the most common pathogens causing respiratory infections. Urinary tract infections were most frequently caused by MDR Escherichia coli and K. pneumoniae. The overall in-hospital mortality rate of COVID-19 patients was 46.9% (237/505), while 78.7% (59/75) of patients with bacterial infections died. Infection was significantly associated with death (OR 6.01, 95% CI = 3.03–11.92, p-value <0.0001) and a longer hospital stay (p < 0.0001). Multivariate logistic regression analysis showed that Age (OR = 1.04, 95% CI = 1.03–1.06, p-value <0.0001), Sex male (OR = 1.70, 95% CI = 1.08–2.70, p-value <0.0001), Spo2 (OR = 1.99, 95% CI = 1.18–3.38, p-value = 0.010) and Ferritin (OR = 2.33, 95% CI = 1.37–3.97, p-value = 0.002) were independent risk factors associated with in-hospital mortality. Furthermore, 95.3% (221/232) of patients who were intubated died.ConclusionOur findings demonstrate that bacterial infection due to MDR Gram-negative bacteria associated with COVID-19 has an expressive impact on increasing the case mortality rate, reinforcing the importance of the need for surveillance and strict infection control rules to limit the expansion of almost untreatable microorganisms.

Prognostic value of transient ischemic dilatation by 13N-ammonia PET MPI for short-term outcomes in patients with non-obstructive CAD

Abstract Objective Transient ischaemic dilatation (TID) had incremental diagnostic and prognostic value in obstructive coronary artery disease (CAD), but its clinical significance in patients with non-obstructive CAD remains unknown. We aimed to explore the prognostic value of TID in patients with non-obstructive CAD by 13N-ammonia PET imaging. Methods We retrospectively studied 131 consecutive patients with non-obstructive CAD undergoing one-day rest-stress 13N-ammonia PET myocardial perfusion imaging (MPI). TID was automatically generated using CardIQ Physio software. The receiver operative characteristic (ROC) curve was used to determine the optimal threshold of TID. The follow-up outcome was major adverse cardiac events (MACE), a composite of re-hospitalization for heart failure or unstable angina, late revascularization, non-fatal myocardial infarction, and cardiac death. Cardiac event-free survivals for normal and abnormal TID were compared using Kaplan–Meier plots and log-rank tests. Results During a median follow-up of 42.08 ± 17.67 months, 22 (16.7%) patients occurred MACE. The optimal cut-off value of TID was 1.03 based on MACE. Our preliminary outcome analysis suggests that TID-abnormal subjects had a lower overall survival probability. Furthermore, our multivariate analysis reveals abnormal TID was the only independent predictor for MACE in non-obstructive CAD. In the subgroup analysis, an abnormal TID was an independent predictor for MACE in patients with abnormal perfusion patterns. Conclusion Among patients with non-obstructive CAD, PET-derived TID ≥ 1.03 may identify those with a high risk of subsequent MACE independently. It was also an independent risk factor for poor prognosis in patients with abnormal perfusion. Graphical abstract CAD coronary artery disease, PET positron emission tomography, MPI myocardial perfusion imaging, TID transient ischaemic dilatation, MACE major adverse cardiac events, ROC receiver operative characteristic.

Neutrophil-to-lymphocyte ratio as a predictor of cardiovascular mortality in cancer survivors

This study aims to evaluate the neutrophil-to-lymphocyte ratio (NLR) as a predictive biomarker for cardiovascular mortality among cancer patients, utilizing data from the National Health and Nutrition Examination Survey (NHANES). From the NHANES dataset (2007–2018), we analyzed 4974 cancer survivors, investigating the prognostic significance of NLR for all-cause, cardiovascular, and cancer-specific mortality. Survival outcomes were analyzed using Cox regression and Kaplan–Meier methods. Optimal NLR cutoffs were identified as 2.61 for differentiating the higher NLR group from lower NLR group. Elevated NLR levels significantly correlated with increased all-cause mortality (HR 1.11, 95% CI 1.07–1.14, P < 0.001) and cardiovascular mortality (HR 1.14, 95% CI 1.08–1.21, P < 0.001) in adjusted models. Subgroup analyses revealed that age, sex, smoking status, and hypertension significantly influence NLR’s association with cardiovascular mortality. Specific cancers including breast, prostate, non-melanoma skin, colon and melanoma experience increased all-cause and cardiovascular mortality in the higher NLR group compared to lower NLR group. Elevated NLR is a significant predictor of increased mortality in cancer patients, particularly for cardiovascular outcomes. These findings support that NLR acts as a pivotal prognostic tool with significant implications for clinical practice in the realm of cardio-oncology.

Chromosomal instability is associated with prognosis and efficacy of bevacizumab after resection of colorectal cancer liver metastasis

Introduction Individualized treatment of colorectal cancer liver metastases (CRLM) remains challenging due to differences in the severity of metastatic disease and tumour biology. Exploring specific prognostic risk subgroups is urgently needed. The current study aimed to investigate the prognostic value of chromosomal instability (CIN) in patients with initially resectable CRLM and the predictive value of CIN for the efficacy of bevacizumab. Methods Ninety-one consecutive patients with initially resectable CRLM who underwent curative liver resection from 2006 to 2018 at Sun Yat-sen University Cancer Center were selected for analysis. CIN was evaluated by automated digital imaging systems. Immunohistochemistry (IHC) was performed to detect interleukin-6 (IL-6), vascular endothelial growth factor A (VEGFA) and CD31 expression in paraffin-embedded specimens. Recurrence-free survival (RFS) and overall survival (OS) were analysed using the Kaplan–Meier method and Cox regression models. Results Patients with high chromosomal instability (CIN-H) had a worse 3-year RFS rate (HR, 1.953; 95% CI, 1.001–3.810; p = 0.049) and a worse 3-year OS rate (HR, 2.449; 95% CI, 1.150–5.213; p = 0.016) than those with low chromosomal instability (CIN-L). CIN-H was identified as an independent prognostic factor for RFS (HR, 2.569; 95% CI, 1.078–6.121; p = 0.033) and OS (HR, 3.852; 95% CI, 1.173–12.645; p = 0.026) in the multivariate analysis. The protein levels of IL-6, VEGFA and CD31 were upregulated in patients in the CIN-H group compared to those in the CIN-L group in both primary tumour and liver metastases tissues. Among them, 22 patients with recurrent tumours were treated with first-line bevacizumab treatment and based on the clinical response assessment, disease control rates were adversely associated with chromosomal instability (p = 0.043). Conclusions Our study showed that high chromosomal instability is a negative prognostic factor for patients with initially resectable CRLM after liver resection. CIN may have positive correlations with angiogenesis through expression of IL-6–VEGFA axis and be used as a potential predictor of efficacy of bevacizumab.

FP4.1 - Impact of adjuvant chemotherapy on the 5 Year Overall Survival for non-metastatic colon cancer patients in Bulgaria - a population wide based observational study

Abstract Aim Colon cancer patients who receive adjuvant chemotherapy later in life have lower survival rates. NCCN guidelines recommend the use of adjuvant chemotherapy for patients with non-metastatic colon cancer. Our study's objective was to examine how adjuvant chemotherapy affected the 5-year overall survival (OS) of patients diagnosed with non-metastatic colon cancer in Bulgaria. Methodology This is a retrospective population-wide observational analysis of 8968 cases that was reported as colorectal cancer (CRC) in the Bulgarian National Cancer Registry (BNCR) from 2015 to 2016. The mean and median ages of patients with right colon (RCC) and left colon (LCC) were examined. An analysis was conducted to determine the effect of adjuvant chemotherapy on the 5-year overall survival for non-metastatic colon cancer. To estimate the statistical significance, chi-squared tests, ANOVA, and the Kaplan-Meier curve with log rank were employed. Results In comparison to LCC, RCC had a higher mean age at diagnosis of 68.9 versus 67.41 (p-Value=&amp;lt;0.001). For RCC and LCC, the corresponding median ages at diagnosis were 69 and 68. The 5-year OS for patients with non-metastatic colon cancer who received adjuvant chemotherapy was higher than for patients who did not (67.8% vs. 59%, respectively, p-Value=0.007), according to our study. Adjuvant chemotherapy was given to slightly more than 30% of patients. Conclusion The 5-Year OS for patients with non-metastatic colon cancer is improved by adjuvant chemotherapy, and Bulgaria should follow NCCN guidelines. The implementation of a systematic screening program can be advantageous for Bulgaria as well.

Integrated MRI radiomics, tumor microenvironment, and clinical risk factors for improving survival prediction in patients with glioblastomas.

To construct acomprehensive model for predicting the prognosis of patients with glioblastoma (GB) using aradiomics method and integrating clinical risk factors, tumor microenvironment (TME), and imaging characteristics. In this retrospective study, we included 148 patients (85males and 63females; median age 53years) with isocitrate dehydrogenase-wildtype GB between January 2016 and April 2022. Patients were randomly divided into the training (n = 104) and test (n = 44) sets. The best feature combination related to GB overall survival (OS) was selected using LASSO Cox regression analyses. Clinical, radiomics, clinical-radiomics, clinical-TME, and clinical-radiomics-TME models were established. The models' concordance index (C-index) was evaluated. The survival curve was drawn using the Kaplan-Meier method, and the prognostic stratification ability of the model was tested. LASSO Cox analyses were used to screen the factors related to OS in patients with GB, including MGMT (hazard ratio [HR] = 0.642; 95% CI 0.414-0.997; P = 0.046), TERT (HR = 1.755; 95% CI 1.095-2.813; P = 0.019), peritumoral edema (HR = 1.013; 95% CI 0.999-1.027; P = 0.049), tumor purity (TP; HR = 0.982; 95% CI 0.964-1.000; P = 0.054), CD163 + tumor-associated macrophages (TAMs; HR = 1.049; 95% CI 1.021-1.078; P < 0.001), CD68 + TAMs (HR = 1.055; 95% CI 1.018-1.093; P = 0.004), and the six radiomics features. The clinical-radiomics-TME model had the best survival prediction ability, the C‑index was 0.768 (0.717-0.819). The AUC of 1‑, 2‑, and 3‑year OS prediction in the test set was 0.842, 0.844, and 0.795, respectively. The clinical-radiomics-TME model is the most effective for predicting the survival of patients with GB. Radiomics features, TP, and TAMs play important roles in the prognostic model.

Circulating Galectin-3: A Prognostic Biomarker in Hepatocellular Carcinoma

ABSTRACT Introduction Galectin-3 plays critical roles in the adhesion, proliferation, and differentiation of tumor cells. Recent data have suggested that galectin-3 plays a role in the development of hepatocellular carcinoma (HCC); however, its prognostic value has not been validated. The aim of our study was to evaluate the clinical and prognostic value of galectin-3 in patients with HCC. Methods We prospectively enrolled and collected clinicopathologic data and serum samples from 767 patients with HCC between 2001 and 2014 at The University of Texas MD Anderson Cancer Center. Two hundred patients without HCC were also enrolled and had data collected. The Kaplan-Meier method was used to estimate overall survival (OS) distributions. Results The median OS in this cohort was 14.2 months (95% CI, 12–16.1). At the time of analysis, the 1-year OS rate was 45% (95% CI, 0.4–0.51) among patients with high galectin-3 levels and 59% (95% CI, 0.54–0.63) among patients with low galectin-3 levels. OS was significantly inferior in patients with high galectin-3 levels than in patients with lower galectin-3 levels (median OS: 10.12 vs. 16.49 months; p = 0.0022). Additionally, the multivariate model showed a significant association between high galectin-3 level and poor OS (hazard ratio [HR] = 1.249; 95% CI, 1.005–1.554). Comparison between low (n = 464 patients) and high (n = 302 patients) galectin-3 levels showed that mean serum galectin-3 levels were significantly higher in patients with HCC who had hepatitis C virus (HCV) infection (p = 0.0001), higher Child-Pugh score (CPS) (p = 0.0009), and higher Cancer of the Liver Italian Program (CLIP) score (p = 0.0015). Conclusion Our study shows that serum galectin-3 level is a valid prognostic biomarker candidate.

Association of body composition and systemic inflammation for patients with locally advanced cervical cancer following concurrent chemoradiotherapy

Systemic inflammation and body composition are associated with survival outcomes of cancer patients. This study aimed to examine the combined prognostic value of systemic inflammatory markers and body composition parameters in patients with locally advanced cervical cancer (LACC). Patients who underwent concurrent chemoradiotherapy (CCRT) for LACC at a tertiary referral teaching hospital between January 2010 and January 2018 were enrolled. A predictive model was established based on systemic immune-inflammation index (SII) and computer tomography-derived visceral fat-to-muscle ratio (vFMR). Overall survival (OS) and progression-free survival (PFS) were assessed using the Kaplan-Meier method and Cox regression models. The model performance was assessed using discrimination, calibration, and clinical usefulness. In total, 212 patients were enrolled. The SII and vFMR were closely related, and both independently predicted survival (P < 0.05). A predictive model was established based on the above biomarkers and included three subgroups: high-risk [both high SII (>828) and high vFMR (>1.1)], middle-risk (either high SII or high vFMR), and low-risk (neither high SII nor high vFMR). The 3-year OS (PFS) rates for low-, middle-, and high-risk patients were 90.5% (86.0%), 73.9% (58.4%), and 46.8% (36.1%), respectively (P < 0.05). This model demonstrated satisfactory predictive accuracy (area under the curve values for predicting 3-year OS and PFS were 0.704 and 0.718, respectively), good fit (Hosmer-Lemeshow tests: P > 0.05), and clinical usefulness. Systemic inflammatory markers combined with body composition parameters could independently predict the prognosis of patients with LACC, highlighting the utilization of commonly collected indicators in decision-making processes. The SII and vFMR, as well as their composite indices, were promising prognostic factors in patients with LACC who received definitive CCRT. Future studies are needed to explore novel therapies to improve the outcomes in high-risk patients.

The role of HGH1 in breast cancer prognosis: a study on immune response and cell cycle

BackgroundBreast cancer (BRCA) remains to be among the main causes of cancer-associated mortality in women globally. HGH1 homolog (HGH1) has been reported to be associated with tumor immunity. However, the function of HGH1 in BRCA remains unclear. Therefore, the present study examined the potential role of HGH1 in BRCA.MethodsThe Cancer Genome Atlas (TCGA) databases and Gene Expression Omnibus (GEO) were used to obtain RNA-seq data for BRCA. A protein localization of HGH1 was determined by using the Human Protein Atlas (HPA), and immunohistochemistry (IHC) staining revealed an upregulation in the expression of HGH1 in clinical BRCA tissues. Xenograft mice were used to test tumor growth and HGH1 expression in breast cancer cells. The protein interaction information of HGH1 was analyzed using the GeneMANIA website. Based on univariate Cox regression and Kaplan-Meier methods, we evaluated the role of HGH1 in BRCA prognosis. HGH1-related differentially expressed genes were analyzed using GO, KEGG, and GSEA. We also examined the relationship between HGH1 expression, immune checkpoints, and immune infiltration. CCK-8, EdU, and colony formation assays were used to measure cell proliferation, and western blot analysis was used to evaluate HGH1’s role in BRCA.ResultsIHC results showed that the expression of HGH1 was significantly upregulated in BRCA tissues compared to normal tissues. High levels of HGH1 expression was associated with worse clinical features and a worse prognosis. HGH1 expression was an independent predictor of BRCA outcomes in both univariate and multivariate analyses. Functionally, western blot analysis showed that HGH1 is implicated in cell cycle. As well, knocking down HGH1 significantly reduced BRCA cells’ proliferative abilities. Crucially, HGH1 expression levels were positively correlated with Th2 cell infiltration and negatively correlated with Tcm cell infiltration.ConclusionBiomarkers such as HGH1 can reliably predict prognosis in BRCA patients.

FP4.10 - Oncosurgical Outcome Differences of Left and Right Colonic Cancer Resections Still a Colorectal Enigma

Abstract Aims The study aimed to compare surgical outcomes between right (RCC) and left colonic cancer (LCC) resections at a single centre (DGH) with special reference to 3 and 5-year survival rates. Methods 100 colonic resections (2017-2021) were included. Length of stay (LOS), pathology results and 3 and 5-year survival rates were analysed. The Kaplan-Meier estimate was used for patients within 5 years post-operative. Results 68 RCC and 32 LCC noted. RCC: 37 female, 31 male, median age of 73. 66 R0 resections, 2 R1, none R2. TNM: 52 (86.1%) had T3/4, 26 (38.2%) had N1/2. 20 had extramural venous invasion (EMVI), 26 intramural venous invasion (IMVI), 8 mucinous, 11 perineural invasion. Estimated 3-year survival rate 0.8530, 5-year 0.7766. No local recurrences, 4 subsequent distant metastases within 5 years. LCC: 11 female, 21 male, median age of 67. 23 R0, 2 R1, 2 R2 resections. TNM: 28 (87.5%) had T3/4, 15 (46.9%) had N1/2. 18 EMVI, 11 IMVI, 1 mucinous, 9 perineural invasion. Estimated 3-year survival rate 0.7498, 5-year 0.5965. No local recurrences, 9 subsequent distant metastases within 5 years. Both cohorts’ median LOS similar (6 days). Discussion This study shows higher survival rates in RCC, contradicting acclaimed superiority of LCC survival in literature(1-5). The limited LCCs in this study (during Covid pandemic) being pathologically more advanced, possibly accounts for the statistically significant mortality. A prospective audit of tumour biology and oncological outcome is ongoing with intentions to validate our early observation.

Overall survival prediction of gastric cancer using the gene signature of CT-detected extramural venous invasion combined with M2 macrophages infiltration

BackgroundCT-detected Extramural venous invasion (EMVI) is known as an independent risk factor for distant metastasis in patients with advanced gastric cancer (GC). However, the molecular basis is not clear. In colorectal cancer, M2 macrophages plays a vital role in determining EMVI. This study aimed to investigate the relationship between CT-detected EMVI and the M2 macrophages as well as prognosis predictionusing a radiogenomic approach.MethodWe utilized EMVI-related genes (from mRNA sequencing of 13 GC samples correlated with EMVI score by spearman analysis, P < 0.01) to overlap the co-expression genes of WGCNA module and M2 macrophages related genes (from mRNA data of 371 GC patients in TCGA database), generating a total of 136 genes. An EMVI-M2-prognosis-related hub gene signature was constructed by COX and least absolute shrinkage and selection operator (LASSO) analysis from a training cohort TCGA database (n = 371) and validated it in a validation cohort from GEO database (n = 357). High- and low-risk groups were divided by hub gene (EGFLAM and GNG11) signature-derived risk scores. We assessed its predictive ability through Kaplan-Meier (K-M) curve and COX analysis. Furthermore, we utilized ESTIMATE to detect tumor mutation burden (TMB) and evaluate sensitivity to immune checkpoint inhibitors (ICIs). Expression of hub genes was tested using western blotting and immunohistochemistry (IHC) analysis.ResultsThe overall survival (OS) was significantly reduced in the high-risk group (Training/Validation: AUC = 0.701/0.620; P < 0.001/0.003). Furthermore, the risk score was identified as an independent predictor of OS in multivariate COX regression analyses (Training/Validation: HR = 1.909/1.928; 95% CI: 1.225–2.974/1.308–2.844). The low-risk group exhibited significantly higher TMB levels (P = 1.6e− 07) and greater sensitivity to ICIs. Significant higher expression of hub-genes was identified on multiple GC cell lines and original samples. Hub-genes knockdown in gastric cancer cell lines inhibited their proliferation, metastatic and invasive capacity to varying degrees. In vivo experiments indicate that EGFLAM, as one of the hub genes, its high expression can serve as a biomarker for low response to immunotherapy.ConclusionOur study demonstrated EMVI-M2 gene signature could effectively predict the prognosis of GC tissue, reflecting the relationship between EMVI and M2 macrophages.

FDA Approval Summary: Belzutifan for Patients with Advanced Renal Cell Carcinoma.

On December 14, 2023, the United States Food and Drug Administration (FDA) approved belzutifan (Welireg, Merck & Co., Inc.) for patients with advanced renal cell carcinoma (RCC) following a programmed death receptor-1 or programmed death-ligand 1 (PD-1/PD-L1) inhibitor and a vascular endothelial growth factor tyrosine kinase inhibitor (VEGF-TKI). FDA granted traditional approval based on LITESPARK-005 (NCT04195750), an open-label, randomized, head-to-head trial of 746 patients with advanced RCC that progressed following both a PD-1/PD-L1 inhibitor and a VEGF-TKI. Patients were randomized (1:1) to receive belzutifan or everolimus. The primary endpoints were progression-free survival (PFS) assessed by blinded independent central review (BICR) and overall survival (OS). A statistically significant improvement in PFS was demonstrated for belzutifan compared with everolimus [hazard ratio (HR)=0.75 (95% CI: 0.63, 0.90); 1-sided p-value=0.0008]. Kaplan-Meier curves reflected non-proportional hazards with similar median PFS estimates of 5.6 months (95% CI: 3.9, 7.0) in the belzutifan arm and 5.6 months (95% CI: 4.8, 5.8) in the everolimus arm. While not reaching full maturity, OS results appeared to show a favorable trend in the belzutifan arm compared to everolimus [HR=0.88 (95% CI: 0.73, 1.07)]. The confirmed objective response rate by BICR was 22% and 3.6% in belzutifan and everolimus arms, respectively. Observed toxicities differed between treatment arms, but drug discontinuations and interruptions due to treatment-emergent adverse events were lower on the belzutifan arm compared to the everolimus arm, and a descriptive analysis of patient-reported symptom and functional outcomes was suggestive of favorable tolerability for belzutifan compared to everolimus.

Integrative radiopathomics model for predicting progression-free survival in patients with nonmetastatic nasopharyngeal carcinoma

PurposeTo construct an integrative radiopathomics model for predicting progression-free survival (PFS) in nonmetastatic nasopharyngeal carcinoma (NPC) patients.Methods357 NPC patients who underwent pretreatment MRI and pathological whole-slide imaging (WSI) were included in this study and randomly divided into two groups: a training set (n = 250) and validation set (n = 107). Radiomic features extracted from MRI were selected using the minimum redundancy maximum relevance and least absolute shrinkage and selection operator methods. The pathomics signature based on WSI was constructed using a deep learning architecture, the Swin Transformer. The radiopathomics model was constructed by incorporating three feature sets: the radiomics signature, pathomics signature, and independent clinical factors. The prognostic efficacy of the model was assessed using the concordance index (C-index). Kaplan-Meier curves for the stratified risk groups were tested by the log-rank test.ResultsThe radiopathomics model exhibited superior predictive performance with C-indexes of 0.791 (95% confidence interval [CI]: 0.724–0.871) in the training set and 0.785 (95% CI: 0.716–0.875) in the validation set compared to any single-modality model (radiomics: 0.619, 95% CI: 0.553–0.706; pathomics: 0.732, 95% CI: 0.662–0.802; clinical model: 0.655, 95% CI: 0.581–0.728) (all, P < 0.05). The radiopathomics model effectively stratified patients into high- and low-risk groups in both the training and validation sets (P < 0.001).ConclusionThe developed radiopathomics model demonstrated its reliability in predicting PFS for NPC patients. It effectively stratified individual patients into distinct risk groups, providing valuable insights for prognostic assessment.

Nine-year survival after intertrochanteric fracture in elderly with chronic kidney disease

The outcome of this study was to identify 9-year survivors of intertrochanteric fracture at each stage of chronic kidney disease (CKD) and to investigate the risk factors associated with mortality following surgery with proximal femoral nail anti-rotation (PFNA). 443 elderly intertrochanteric fractures underwent PFNA fixation were recruited. Mortality rate was identified until 9 years. We compared the survival time of hip fracture in each stage of CKD. A regression analysis was used to determine the association between risk factors and one-year mortality. The overall median survival time was 7.1 years. The Kaplan–Meier curve was significantly different in each CKD stage especially in CKD5. In addition, the incidence rate of mortality was highest in CKD 5 (17.4%) and the median survival time in CKD 5 was 3.3 years. The multivariate analysis demonstrated that heart disease, operative time > 60 min, presence of pulmonary embolism, and poor to fair Harris hip score were significantly increased mortality. CKD stage 5 is associated with the highest mortality rate and the shortest median time of survival during the 9-year follow up. Patients who have high risk should focus on long-term care planning, including the counseling for their healthcare providers and families.

Prevalence and outcomes of gastrointestinal manifestations in an Australian Scleroderma cohort.

The gastrointestinal tract (GIT) is the most commonly affected internal organ in systemic sclerosis (SSc). We sought to determine the prevalence and impact of GIT symptoms on survival and patient-reported outcomes. 907 consecutive patients from the Australian Scleroderma Cohort Study (ASCS) who had prospectively completed the University of California Los Angeles Scleroderma Clinical Trials Consortium Gastrointestinal Tract 2.0 questionnaire (UCLA GIT) between 2015 and 2021 were included. The association between UCLA GIT scores and physical function (SHAQ), QoL (SF-36), mood (PROMIS anxiety and depression domains), fatigue (FACIT-fatigue score) and employment was investigated using multivariable population-averaged panel models using Generalized Estimating Equations (GEE). Kaplan-Meier curves and multivariable Cox proportional hazard regression model were used to evaluate survival according to total UCLA GIT scores. GIT symptoms were reported in 87% of participants with 46-52% reporting moderate to very severe symptoms of reflux, distension, diarrhoea and constipation. Higher total UCLA GIT scores were associated with worse QoL, physical function, fatigue, anxiety and depression (p<0.001). In multivariable GEE analysis, moderate and severe to very severe total scores, reflux and distension scores were associated with worse physical function, QoL, fatigue, anxiety and depression compared to those with mild scores (p<0.05). Patients with severe total scores and diarrhoea scores were more likely to be unemployed compared to those with mild scores (p<0.05). UCLA GIT total scores were not independently associated with mortality in our cohort. GIT manifestations are common in SSc and negatively impact QoL, physical function and employment but are not directly associated with increased mortality.

MRI-measured periprostatic to subcutaneous adipose tissue thickness ratio as an independent risk factor in prostate cancer patients undergoing radical prostatectomy

The purpose of this study is to evaluate whether the periprostatic adipose tissue thickness (PPATT) is an independent prognostic factor for prostate cancer patients after laparoscopic radical prostatectomy (LRP). This retrospective cohort study included consecutive prostate cancer patients who underwent LRP treatment at Wuhan Union Hospital from June 2, 2016, to September 7, 2023. PPATT was defined as the thickness of periprostatic fat and was obtained by measuring the shortest vertical distance from the pubic symphysis to the prostate on the midsagittal T2-weighted MR images. Subcutaneous adipose tissue thickness (SATT) was obtained by measuring the shortest vertical distance from the pubic symphysis to the skin at the same slice with PPATT. The primary outcome of the study was biochemical recurrence (BCR), and the secondary outcome was overall survival (OS). Multivariable Cox regression analysis was used to identify independent prognostic factors for prostate cancer survival and prognosis. Based on the optimal cutoff value, 162 patients were divided into a low PPATT/SATT group (n = 82) and a high PPATT/SATT group (n = 80). During the entire follow-up period (median 23.5 months), 26 patients in the high PPATT/SATT group experienced BCR (32.5%), compared to 18 in the low PPATT/SATT group (22.0%). Kaplan–Meier curve analysis indicated that the interval to BCR was significantly shorter in the high PPATT/SATT group (P = 0.037). Multivariable Cox regression analysis revealed that an increase in the PPATT/SATT ratio was associated with BCR (hazard ratio: 1.90, 95% CI, 1.03–3.51; P = 0.040). The PPATT/SATT ratio is a significant independent risk factor for BCR after LRP for prostate cancer patients.

Minimally invasive technique facilitates early extubation after cardiac surgery: a single-center retrospective study

BackgroundPostoperative time to extubation plays a role in prognosis after heart valve surgery; however, its exact impact has not been clarified. This study compared the postoperative outcomes of minimally invasive surgery and conventional sternotomy, focusing on early extubation and factors influencing prolonged mechanical ventilation.MethodsData from 744 patients who underwent heart valve surgery at the Zhejiang Provincial People’s Hospital between August 2019 and June 2022 were retrospectively analyzed. The outcomes in patients who underwent conventional median sternotomy (MS) and minimally invasive (MI) video-assisted thoracoscopic surgery were compared using inverse probability of treatment weighting (IPTW) and Kaplan–Meier curves. Clinical data, including surgical data, postoperative cardiac function, postoperative complications, and intensive care monitoring data, were analyzed.ResultsAfter propensity score matching and IPTW, 196 cases of conventional MS were compared with 196 cases of MI video-assisted thoracoscopic surgery. Compared to patients in the conventional MS group, those in the MI video-assisted thoracoscopic surgery group in the matched cohort had a higher early postoperative extubation rate (P < 0.01), reduced incidence of postoperative pleural effusion (P < 0.05), significantly shorter length of stay in the intensive care unit (P < 0.01), shorter overall length of hospital stay (P < 0.01), and lower total cost of hospitalization (P < 0.01).ConclusionsSuccessful early tracheal extubation is important for the intensive care management of patients after heart valve surgery. The advantages of MI video-assisted thoracoscopic surgery over conventional MS include significant reductions in the duration of use of mechanical ventilation support, reduced length of intensive care unit stay, reduced total length of hospitalization, and a favorable patient recovery rate.

The impact of inter-cycle treatment delays on overall survival in patients with advanced-stage ovarian cancer.

Chemotherapy forms the cornerstone of systemic treatment for advanced ovarian cancer, extending overall survival; however, drug-related toxicity can lead to treatment delays, potentially diminishing treatment efficacy. This study evaluated the impact of treatment delays on all-cause mortality of patients with ovarian cancer, to better inform decisions on patient management. This retrospective, population-based cohort study included 1517 women with advanced-stage ovarian cancer, receiving first-line adjuvant or neoadjuvant chemotherapy in 2014 and 2015. The frequency of inter-cycle delays >7 dayswas calculated using drug administration dates. Kaplan-Meier estimates were used to compare 2-year overall survival (OS) between patients who were delayed and those treated to schedule. Cox proportional hazards regression was used to investigate the impact of treatment delay on all-cause mortality. Inverse probability of treatment weighting propensity scores were used to adjust for confounding variables. Delays >7 days occurred in 35.3% of patients. Two-year OS probability was 62.7% in patients who experienced treatment delays >7 days (95% CI, 58.7-66.9) compared to 69.1% in those treated to schedule (95% CI, 66.2-72.0). Delays were not significantly associated with all-cause mortality when adjusted for confounders (HR 1.00 95% CI, 0.83-1.20, P = .9). Delays to chemotherapy treatment were not significantly associated with worsened survival in patients with advanced-stage ovarian cancer. These results can inform clinical decision making that prioritize toxicity management and quality of life for those treated with chemotherapy.