Multivariate Cox Proportional Analysis Research Articles

Effect of homologous recombination deficiency on survival in patients with metastatic colorectal cancer with KRAS mutations.

252 Background: Metastatic colorectal cancer (mCRC) patients exhibit intertumoral genetic heterogeneity, making it difficult to apply precision medicine. In the molecular genetic profile of mCRC, there are relatively few other gene alterations that significantly impact treatment decisions beyond KRAS and MSI status. We aim to investigate the prognostic impact of Homologous recombination deficiency (HRD)-related genetic alterations in mCRC patients, focusing on how mutation status influences on patient outcomes. Methods: The analysis included 364 mCRC patients who underwent comprehensive genomic profiling at Korea University Anam Hospital from Sep. 2016 to Dec. 2020. HRD was defined by the presence of pathogenic variants in genes including ATM, ATR, BARD1, BRCA1/2, BRIP1, CDK12, CHEK2, FANCA, MRE11A, PALB2, RAD50/51. Overall survival (OS) and progression-free survival (PFS) were evaluated using the Kaplan-Meier method. Multivariate Cox proportional hazards regression analyses were performed to assess the independent impact of HRD status. Results: Of the total cohort, 181 of patients (49.78%) harbored KRAS mutations. HRD gene mutations were identified in 38 of patients (10.4%) of patients, predominantly in ATM, BRCA 1/2, ARID1A genes. KRAS-HRD co-mutations were present in 18 of patients (4.7%). There is no significant difference in HRD status between the KRAS mutant and wild-type groups (p=0.73). While first-line treatment PFS was independent of KRAS mutational status (wt 10.8 vs. mut 9.6 months, p=0.31), it was significantly associated with HRD gene mutation status (16.2 vs. 10.6 months, p=0.001). OS was similar with KRAS mutations (34.7 vs. 32.9 months, p=0.72) and HRD mutations (34.7 vs. 39.1 months, p=0.73). However, patients with both KRAS and HRD mutations had significantly worse OS compared to those with either KRAS and HRD mutation (21.3 vs. 36.7 vs. 65.3 months, p=0.034, <0.001). A multivariate analysis was performed to evaluate factors affecting OS in mCRC patients. Among the variables, metastasectomy, which 44% of patients underwent, had a significantly low HR (=0.28) and would contributed to more favorable outcomes when evaluating OS. Neither KRAS nor HRD mutation alone was a significant prognostic factor, but their co-mutation was significantly associated with poor survival (HR=2.39, p=0.048). Conclusions: Poor OS in patients with KRAS-HRD co-mutations, despite metastasectomy, highlights the need for additional treatment strategies beyond surgery. Future studies with larger sample sizes and analyses stratified by metastasectomy status are necessary to strengthen these findings. Variables HR (95% CI) p-value Metastasis site Liver 2.16 (1.60 – 2.92) < 0.001 Peritoneum 1.52 (1.01 – 2.11) 0.013 Bone 1.69 (0.96 – 2.97) 0.067 Metastasectomy 0.28 (0.47 – 0.74) < 0.001 KRAS 1.03 (0.77 – 1.37) 0.826 HRD 0.75 (0.40 – 1.41) 0.367 Co-mutation 2.39 (1.01 – 5.66) 0.048

Association Between Liver Fibrosis and Risk of Incident Stroke and Mortality: ALarge Prospective Cohort Study.

There is a well-established relationship between liver conditions and cardiovascular diseases. However, uncertainty persists regarding the contribution of liver fibrosis to major stroke types including ischemic stroke, intracerebral hemorrhage, and subarachnoid hemorrhage at the population level. In this large prospective cohort study, participants without previous stroke or coronary heart disease at baseline from the UK Biobank were included. We identified participants at high probability of advanced liver fibrosis using the Fibrosis-4 index >2.67 or aspartate aminotransferase to platelet ratio index ≥1.0. Multivariable Cox proportional hazard regression analyses were conducted to estimate hazard ratios (HRs) for liver fibrosis with the incidence of major stroke types, stroke-related death, and all-cause death. Among 379 953 participants (mean age, 56.2 [SD, 8.1] years; 44.6% men), 7396 (1.9%) had a Fibrosis-4 index >2.67 at baseline. During a median follow-up of 12.75 (interquartile range, 12.03-13.48) years, 7143 (1.9%) incident stroke cases were documented. Advanced liver fibrosis assessed by the Fibrosis-4 index was associated with an increased risk of ischemic stroke (HR, 1.94 [95% CI, 1.70-2.22]), intracerebral hemorrhage (HR, 2.14 [95% CI, 1.63-2.81]), subarachnoid hemorrhage (HR, 1.90 [95% CI, 1.27-2.84), stroke-related death (HR, 2.20 [95% CI, 1.73-2.80]), and all-cause death (HR, 2.59 [95% CI, 2.46-2.73]). Using the aspartate aminotransferase to platelet ratio index as an alternative score, liver fibrosis was correlated with magnified risk of intracerebral hemorrhage (HR, 3.76 [95% CI, 2.38-5.93]) and subarachnoid hemorrhage (HR, 3.05 [95% CI, 1.51-6.13]) compared with ischemic stroke (HR, 1.58 [95% CI, 1.17-2.14]). Restricted cubic spline analysis showed nonlinear associations of the Fibrosis-4 index and aspartate aminotransferase to platelet ratio index with stroke incidence and all-cause death. Liver fibrosis is associated with increased risk of incident stroke and death among people without previous stroke or cardiovascular events, with particularly greater risk of intracerebral hemorrhage and subarachnoid hemorrhage. Noninvasive indices of liver fibrosis may serve as an easily accessible marker to detect individuals facing elevated risk of stroke and death in the primary prevention settings.

Timing of acute decompensated heart failure in patients with heart failure and mildly reduced ejection fraction.

This study investigates the prognosis of acute decompensated heart failure (ADHF) on admission (i.e., primary ADHF) as compared to ADHF onset during course of hospitalization (i.e., secondary ADHF) in patients hospitalized with heart failure with mildly reduced ejection fraction (HFmrEF). Limited data regarding the prognostic impact of the timing of onset of ADHF is available. Consecutive patients with HFmrEF and ADHF were retrospectively included at one institution from 2016 to 2022. Patients with primary ADHF were compared to patients with secondary ADHF with regard to the primary endpoint all-cause mortality at 30 months. Kaplan-Meier, uni- and multivariable Cox proportional regression analyses were applied for statistics. From a total of 484 patients hospitalized with HFmrEF and ADHF, 67.98% (n = 329) were admitted with primary ADHF. Patients with secondary ADHF had higher rates of concomitant acute myocardial infarction, alongside with a higher extend of coronary artery disease. The risk of all-cause mortality at 30months was not affected by the timing of ADHF (hazard ratio (HR) = 0.853; 95% confidence interval (CI) 0.653-1.115; p = 0.246). However, patients with primary ADHF were associated with a higher risk of HF-related rehospitalization at 30months (HR = 2.513; 95% CI 1.555-4.065; p = 0.001), which was still evident after multivariable adjustment (HR = 2.347; 95% CI 1.418-3.883; p = 0.001). The timing of onset of ADHF was not associated with long-term mortality in HFmrEF, however primary ADHF was associated with a higher risk of HF-related rehospitalization.

Prognostic impact of psychoeducation program completion on inpatients with schizophrenia: a pilot cohort study

BackgroundPsychoeducation programs can reduce the risk of recurrence and readmission in patients with schizophrenia. However, almost all previous studies of program efficacy have included only patients completing the program, which may not be possible in all cases. The objective of this pilot cohort study was to compare the prognoses of inpatients with schizophrenia who did or did not complete a well-established institutional psychoeducation program.MethodsThis study is a pilot cohort study, and the participants were 32 inpatients in the psychiatric acute care ward. Among these patients, 18 completed the institutional psychoeducation program by discharge, whereas 14 missed one or more sessions for various reasons. The primary outcome was the duration of outpatient treatment (DOT) during the 5-year follow-up period, and the secondary outcomes were comparisons of the risk of all-cause discontinuation for outpatient treatment and correlations between the program participation rates and DOT.ResultsDOT was significantly longer in the program completion group than in the noncompletion group (918.2 (174.3) days vs. 225.5 (35.7) days, p = 0.001), and multivariate Cox proportional hazards regression analysis revealed that program noncompliance was associated with a 4.450-fold (p = 0.002) greater risk of discontinuation of outpatient treatment according to multivariate analysis. A significant weak correlation was found for DOT and rates of sessions admitted to the programme (Pearson's r = 0.384, p = 0.030).ConclusionsCompletion of a psychoeducation program could enhanced the success of outpatient treatment. As psychoeducation and related factors may have a positive effect of the prognosis after discharge, inpatient psychoeducation programs should be flexible enough to provide opportunities for completion.

Prognostic Implications of Sex in Patients With Heart Failure With Mildly Reduced Ejection Fraction: Results From a Large-Scaled Registry.

The study investigates the prognostic impact of sex and sex-related differences in patients hospitalized with heart failure with mildly reduced ejection fraction (HFmrEF). More data regarding the characterization of patients and their outcomes in the presence of HFmrEF are needed. Consecutive patients hospitalized with HFmrEF (ie, left ventricular ejection fraction 41%-49% and signs or symptoms of HF) were retrospectively included at one institution from 2016 to 2022. Female patients were compared with male patients with regard to the primary end point of all-cause mortality at 30 months (median follow-up). Statistical analyses comprised Kaplan-Meier, multivariable Cox proportional regression analyses and propensity score matching. From a total of 2184 patients hospitalized with HFmrEF, 64.6% were male. Female patients with HFmrEF were older than male patients (median age 78 versus 73 years; P=0.001) and had lower rates of ischemic cardiomyopathy (46.6% versus 63.6%; P=0.001). Within the entire study cohort, sex was not associated with the risk of all-cause mortality (hazard ratio [HR], 0.931 [95% CI, 0.797-1.088]; P=0.372). However, male sex was associated with a lower risk of HF-related rehospitalization at 30 months (HR, 0.761 [95% CI, 0.600-0.966]; P=0.026), which was confirmed after multivariable adjustment (HR, 0.759 [95% CI, 0.592-0.973]; P=0.029) and propensity score matching (HR, 0.722 [95% CI, 0.539-0.967]; P=0.029). Although almost two thirds of patients hospitalized with HFmrEF were male, sex was no predictor for the risk of all-cause mortality at 30 months. However, female sex was associated with a higher risk of HF-related rehospitalization. URL: https://clinicaltrials.gov; Unique identifier: NCT05603390.

Comparison of BCG Tokyo172 Strain Induction Therapy Between Low Dose and Standard Dose for Non-Muscle Invasive Bladder Cancer: Intravesical Instillation of BCG Tokyo172 Strain.

The aim of this study was to identify factors that predict recurrence by comparing low-dose and standard-dose Bacillus Calmette-Guérin (BCG) induction therapy in patients with non-muscle invasive bladder cancer (NMIBC). A total of 273 consecutive NMIBC patients who received low-dose (40 mg) or standard-dose (80 mg) BCG intravesical instillation therapy between January 2004 and December 2023 were analyzed. Recurrence-free survival (RFS) rates were assessed using the Kaplan-Meier method with the log-rank test. Univariate and multivariate Cox proportional hazards regression analyses were used to identify independent predictors of recurrence based on the Club Urológico Español de Tratamiento Oncológico (CUETO) criteria. The log-rank test showed that older age, low BCG dose, number of tumors, and a history of recurrence increased the risk of recurrence significantly. Regarding older patients, recurrence rates were similar between the two dose groups. However, younger patients had significantly lower recurrence rates with standard-dose BCG compared to low-dose BCG. Multiple Cox regression analysis confirmed that older age, low-dose BCG, greater than three tumors, and a history of recurrence were significant predictors of recurrence. In this study, we found that low-dose BCG induction therapy was associated with higher relapse rates compared with standard doses, especially in younger patients. Age-related differences in the immune response to BCG may influence these relapse patterns.

Quadrant, necrosis, and infection criteria for the risk stratification of walled-off necrosis: external validation using multi-institutional data.

Endoscopic ultrasound-guided peripancreatic fluid drainage (EUS-PFD) with on-demand endoscopic necrosectomy, increasingly utilized to manage walled-off necrosis (WON), is associated with substantial morbidity and mortality. This multicenter study aimed to externally validate recently developed quadrant (an abdominal quadrant distribution), necrosis, and infection (QNI) criteria for risk stratification in this setting. Of 423 patients with pancreatic fluid collections treated in a large multi-institutional cohort between 2010 and 2020, 212 with available preprocedural computed tomography images were included. Clinical outcomes between high- and low-risk groups defined according to QNI criteria were compared. The clinical success rate did not differ significantly between the QNI-high and QNI-low groups (74.4% vs. 83.5%, respectively; P = 0.12). Time to clinical success was longer in the QNI-high group compared with the QNI-low group (median, 68 vs. 46 days, respectively; P = 0.0016). Compared with the QNI-low group, the QNI-high group was associated with higher rates of percutaneous interventions, direct endoscopic necrosectomy, mortality, and adverse events. The QNI-high group was independently associated with time to clinical success (hazard ratio 0.64, 95% confidence interval 0.46-0.87; P =0.005) in multivariable Cox proportional hazards regression analysis, and with the risk of ≥grade III adverse events (odds ratio 2.93, 95% confidence interval 1.04-8.20; P = 0.04) in multivariable logistic regression analysis. The QNI criteria effectively stratified time to clinical success and the risk of adverse outcomes for patients receiving EUS-PFD of WON. Further investigations could elucidate appropriate management strategies based on QNI-based risk stratification.

Composite dietary antioxidant index is inversely and nonlinearly associated with cardiovascular disease, atherosclerotic cardiovascular disease, and cardiovascular mortality in people with dyslipidemia: evidence from NHANES 2001-2018.

Dyslipidemia is a major risk factor for cardiovascular disease (CVD) and atherosclerotic CVD (ASCVD). The composite dietary antioxidant index (CDAI), an emerging measure of combined dietary antioxidant exposure, may provide insights into the relationship between diet and CVD/ASCVD outcomes. We aimed to explore the association between CDAI and the prevalence of CVD/ASCVD, as well as CVD mortality in individuals with dyslipidemia. CDAI was assessed by integrating dietary vitamins A, C, E, zinc, selenium, and carotenoids. Dyslipidemia was diagnosed according to widely established criteria. Data on CVD/ASCVD were obtained through self-reports, while CVD mortality was obtained through prospective matching participant records with the National Death Index database. Multivariate logistic regression analysis and Cox proportional hazards regression analysis were used to explore these associations and to calculate odds ratios [OR], hazard ratios [HR], and 95% confidence intervals [CI], respectively. A total of 23,126 participants with dyslipidemia from NHANES 2001-2018 were included. After adjusting for potential confounders, CDAI was inversely associated with the prevalence of both CVD and ASCVD in dyslipidemia populations (OR and 95% CI 0.979 (0.964, 0.995) and 0.977 (0.961, 0.993), respectively). Similar associations were observed between CDAI and specific types of CVD. CDAI was also inversely associated with CVD mortality in dyslipidemia participants (HR = 0.957, 95% CI = 0.939-0.976, p < 0.0001). Restricted cubic spline and threshold effects analyses indicated that CDAI was nonlinearly associated with CVD/ASCVD, with significant associations occurring only when CDAI≤0; however, the association of CDAI with CVD mortality was observed only when CDAI > -2. Furthermore, age, sex, and drinking were found to modify the association of CDAI with CVD/ASCVD, while body mass index influenced the relationship between CDAI and CVD mortality. CDAI was inversely and nonlinearly associated with both CVD/ASCVD events and CVD mortality in dyslipidemic populations. These findings highlight the potential of antioxidant dietary patterns to alleviate the CVD burden in these populations and underscore the importance of personalized strategies.

Sex-Based Differences and Outcomes in Unselected Patients Undergoing Coronary Angiography.

Background: The study investigates sex-related differences and outcomes in unselected patients undergoing invasive coronary angiography (CA). Sex-based differences with regard to baseline characteristics and management of patients with cardiovascular disease have yet been demonstrated. However, their impact on long-term outcomes in unselected patients undergoing CA remains unknown. Methods: Consecutive patients undergoing invasive CA from 2016 to 2022 were included at one institution. Prognosis of male and female patients undergoing CA was investigated with regard to the primary endpoint of rehospitalization for heart failure (HF) at 36 months. Secondary endpoints comprised the risk of acute myocardial infarction (AMI) and coronary revascularization at 36 months, as well as in-hospital all-cause mortality. Statistical analyses included Kaplan-Meier analyses, as well as uni- and multivariable Cox proportional regression analyses. Results: From 2016 to 2022, 7691 patients undergoing CA were included (males: 65.1%; females: 34.9%). Males had a higher prevalence of coronary artery disease (CAD) (76.2% vs. 57.4%; p = 0.001), alongside a higher prevalence of 3-vessel CAD compared to females (33.9% vs. 20.3%; p = 0.001). The risk of rehospitalization for HF at 36 months was higher in males compared to females (22.4% vs. 20.3%; p = 0.036; HR = 1.127; 95% CI: 1.014-1.254; p = 0.027), which was no longer observed after multivariable adjustment. Male sex was associated with a higher risk of coronary revascularization (9.6% vs. 5.9%; p = 0.001; HR = 1.659; 95% CI: 1.379-1.997; p = 0.001), which was still evident after multivariable adjustment (HR = 1.650; 95% CI 1.341-2.029; p = 0.001). However, neither the risk of AMI at 36 months (8.1% vs. 6.9%; p = 0.077), nor the risk of in-hospital all-cause mortality (6.9% vs. 6.5%; p = 0.689) differed significantly between the two sexes. Conclusions: In consecutive patients undergoing coronary angiography, male sex was independently associated with an increased risk of coronary revascularization, but not HF-related rehospitalization.

Age at Menopause and Development of Type 2 Diabetes in Korea

There is limited evidence regarding the association between age at menopause and incident type 2 diabetes (T2D). To investigate whether age at menopause and premature menopause are associated with T2D incidence in postmenopausal Korean women. This population-based cohort study was conducted among a nationally representative sample from the Korean National Health Insurance Service database of 1 125 378 postmenopausal women without T2D who enrolled in 2009. The median (IQR) follow-up was 8.4 (8.1-8.7) years. Data were analyzed in March 2024. Age at menopause and premature menopause (menopause onset at age <40 years). The primary outcome was incident T2D. Multivariable Cox proportional hazards regression analysis was used to estimate hazard ratios (HRs) and 95% CIs for incident T2D by age at menopause, adjusting for potential confounders. Of 1 125 378 participants (mean [SD] age at enrollment, 61.2 [8.4] years), 113 864 individuals (10.1%) were diagnosed with T2D at least 1 year after enrollment. Women with menopause onset at ages younger than 40 years (premature menopause; HR, 1.13; 95% CI, 1.08-1.18) and ages 40 to 44 years (HR, 1.03; 95% CI, 1.00-1.06) had increased risk of T2D compared with those with onset at age 50 years or older, with adjustment for sociodemographic, lifestyle, cardiometabolic, psychiatric, and reproductive factors; a younger age at menopause was associated with increased risk of developing T2D (P for trend <.001). Body mass index, depressive disorder, and prediabetes modified the association in subgroup analyses; for example, for individuals with premature menopause vs those with menopause at ages 50 years or older, HRs were 1.54 (95% CI, 1.14-2.06) for a BMI less than 18.5 and 1.14 (95% CI, 1.00-1.30) for a BMI of 30 or greater (P < .001), 1.28 (95% CI, 1.12-1.45) for individuals with depression and 1.11 (95% CI, 1.07-1.16) for those without depression (P = .01), and 1.25 (95% CI, 1.18-1.33) for individuals who were not prediabetic and 1.04 (95% CI, 0.99-1.11) those who were prediabetic (P < .001). In this study, premature and early menopause were associated with a higher risk of T2D, highlighting the need for targeted public health strategies aimed at preventing or delaying T2D among postmenopausal women.

Risk and Prognosis of Hepatocellular Carcinoma in Mexican Americans with Type 2 Diabetes Mellitus.

Hepatocellular carcinoma (HCC) disproportionately affects Hispanic persons with higher age-specific incidence and increased mortality rates compared to non-Hispanic Whites. These high rates of incidence and mortality may be explained by the variation in risk factors. Given the high prevalence of type 2 diabetes mellitus (DM) among the Hispanic population, we aimed to assess the risk and prognosis of HCC in Mexican Americans with type 2 DM with consideration of treatment for DM. A case-control study of 241 Mexican American HCC patients and 500healthy controls in Texas was conducted. Multivariable logistic regression analysis was performed to determine the association between type 2 DM and HCC risk while adjusting for other risk factors. Also, a restricted analysis of patients with type 2 DM was conducted to determine the effects of age at onset and duration of DM on HCC risk. Interactions among DM, heavy alcohol consumption, and viral hepatitis infection were examined. Overall survival was examined, and multivariable Cox proportional hazards regression analysis was performed for HCC patients with type 2 DM. The adjusted odds ratio (AOR) for DM was 2.74 (P < 0.01). Compared with patients who had DM for 2-10 years, those who had it for at least 20 years had an AOR of 4.60 (P = 0.04). Metformin use was associated with a reduced risk of death in HCC cases with type 2 DM, with a hazard ratio of 0.72 (P = 0.01) as compared with non-users. Our results demonstrate that type 2 DM was independently associated with increased risk of HCC among Mexican Americans. Metformin use was associated with improved survival among HCC patients with type 2 DM. Type 2 DM significantly increased the risk of HCC alone and in conjunction with other parameters of metabolic syndrome in the Mexican American population after adjusting for other risk factors.

Clinical significance of the estimation of pulmonary-right ventricular uncoupling in patients with transthyretin amyloid cardiomyopathy.

There are few data on the prognostic impact of pulmonary-right ventricular (RV) uncoupling in patients with wild-type transthyretin amyloid cardiomyopathy (ATTRwt-CM). Among the 174 patients who were diagnosed with ATTRwt-CM at Kumamoto University Hospital from 2002 to 2021, 143 patients who met the current Japanese guideline and had sufficient information for two-dimensional speckle tracking echocardiography were retrospectively analysed. During a median follow-up of 1209 days, 39 cardiac deaths occurred. Compared with patients in the non-event group, those in the cardiac death group were significantly older (79.3 ± 6.7 vs. 76.4 ± 6.2, respectively; P < 0.05). Additionally, RV global longitudinal strain (RV-GLS)/systolic pulmonary artery pressure (sPAP), an index of pulmonary-RV uncoupling, was significantly lower in patients in the cardiac death group vs. the non-event group [0.29 (0.18-0.35) vs. 0.40 (0.29-0.57), P < 0.01]. Multivariate Cox proportional hazards regression analysis demonstrated that RV-GLS/sPAP was significantly associated with cardiac death after adjusting for tricuspid annular plane systolic excursion/sPAP (P < 0.01), sPAP (P < 0.05), and conventional prognostic factors including age and hospitalization for heart failure (<0.01), laboratory finding including high-sensitivity cardiac troponin T, and B-type natriuretic peptide (P < 0.01). Receiver operating characteristic analysis showed that the area under the curve for RV-GLS/sPAP for cardiac death was 0.72 and that the best cut off value for RV-GLS/sPAP was 0.34 (sensitivity, 76%; specificity, 65%). In the Kaplan-Meier analysis, patients with ATTRwt-CM who had low vs. high RV-GLS/sPAP (cut-off value 0.34) had a significantly higher probability of cardiac death (P < 0.01). Pulmonary-RV uncoupling has significantly higher prognostic value compared with conventional prognostic factors in ATTRwt-CM.

Association between stress hyperglycemia ratio and mortality in patients with heart failure complicated by sepsis

Individuals afflicted with heart failure complicated by sepsis often experience a surge in blood glucose levels, a phenomenon known as stress hyperglycemia. However, the correlation between this condition and overall mortality remains unclear. 869 individuals with heart failure complicated by sepsis were identified from the Medical Information Mart for Intensive Care-IV (MIMIC-IV) database and categorized into five cohorts based on their stress hyperglycemia ratio (SHR). The primary endpoints evaluated were mortality within the intensive care unit (ICU), all-cause mortality within 28 days, and all-cause mortality during hospitalization. Cox proportional hazards regression and restricted cubic spline analyses were employed to unravel the association between SHR and mortality. The ICU mortality, in-hospital mortality, and 28-day all-cause mortality were 10.01%, 13.69%, and 16.46%, respectively. Multivariable Cox proportional hazards regression analysis revealed a significant association between elevated SHR and all-cause mortality. After adjusting for confounding variables, elevated SHR was significantly associated with increased risk of ICU mortality (hazard ratio [HR] = 1.67; 95% confidence interval [CI], 1.03–2.70)), in-hospital mortality (HR = 1.53; 95% CI, 1.00-2.33)), and 28-day all-cause mortality (HR = 1.49; 95% CI, 1.02–2.17)). Restricted cubic spline analysis demonstrated a significant U-shaped relationship between SHR and the risk of all-cause mortality. This study revealed that stress hyperglycemia ratio is an independent prognostic factor in patients with heart failure complicated by sepsis. Notably, both very high and very low SHR values were associated with increased mortality risk.

Pre-procedural TMAO as a predictor for recurrence of atrial fibrillation after catheter ablation

BackgroundNumerous studies have demonstrated the significance of trimethylamine-N-oxide (TMAO) in the progression of atrial fibrillation (AF). However, the association between TMAO and AF recurrence (RAF) post-catheter ablation is not yet fully understood. This study aims to elucidate the predictive capability of pre-procedural TMAO levels in determining RAF following catheter ablation (CA).MethodsThis study was conducted as a prospective, single-center observational study. Between June 2021 and June 2022, 152 patients from the Department of Cardiology at The Affiliated Huaian No. 1 People’s Hospital of Nanjing Medical University were enrolled. Baseline characteristics and serum TMAO levels were assessed for all participants. Patients with AF who underwent CA were monitored for recurrences of AF using electrocardiography (ECG) or 24-hour Holter monitoring during the follow-up period.ResultsThe study found that serum TMAO levels were significantly higher in persistent AF (PeAF) patients compared to those in sinus rhythm (SR) and paroxysmal AF (PaAF) patients (3.96 ± 1.69 vs. 1.81 ± 0.59, 3.02 ± 1.50 µM, P < 0.001 and P < 0.01, respectively). After a one-year follow-up, 29 (21.2%) AF patients experienced recurrence after CA. Multivariate Cox proportional hazards regression analysis revealed that pre-procedural serum TMAO was an independent predictor of recurrent AF (HR = 1.78, 95% CI = 1.43–2.21, P < 0.001). The receiver operating characteristic (ROC) curve analysis identified a cut-off value of 4.3µM for serum TMAO levels in predicting recurrent AF (area under the curve: 0.835, P < 0.001). The Kaplan-Meier plot demonstrated that patients with TMAO levels greater than 4.3µM had a significantly higher rate of recurrent AF (HR = 13.53, 95% CI = 6.19–29.56, P < 0.001).ConclusionPatients with AF exhibited elevated levels of circulating TMAO compared to patients with SR. The findings suggest a potential role of TMAO in the development of AF, with pre-procedural serum TMAO levels serving as a reliable predictor of recurrence of AF CA.

Cluster analysis and analysis of risk factors for hereditary transthyretin amyloidosis cardiomyopathy

Objective: To explore the clinical characteristics and prognostic value in hereditary transthyretin amyloidosis cardiomyopathy (hATTR-CM) patients based on cluster analysis, and to explore the risk factors for cardiovascular composite events. Methods: This retrospective cohort study included hATTR-CM patients who were admitted to Peking Union Medical College Hospital from January 2000 to January 2024. These patients were divided into two clusters using cluster analysis, based on genetic information, demographic information and clinical information. During the follow-up period, cardiovascular composite events were defined as all-cause death and hospitalization for heart failure. Both cardiovascular composite events and all-cause death were the endpoints. Kaplan-Meier survival curves and log-rank method were used to compare the prognostic significance of cluster analysis subgroups. Univariate and multivariate Cox proportional hazard regression models were used to analyze the risk factors affecting the incidence of cardiovascular composite events. Results: A total of 43 patients were included in this study, 30 were male (69.8%). In cluster 1 (n=27), whose age of onset was (49.9±13.9) years old, 24(88.9%) of them started with neuropathy or gastrointestinal symptoms, and all clinical phenotypes were mixed type (neurological and cardiac). In cluster 2 (n=16), whose age of onset was (59.0±10.6) years old, 15(93.8%) of them started with heart failure symptoms, and 13(81.3%) were pure cardiomyopathy. During the median follow-up time of 2.6 years, a total of 16 patients (37.2%) experienced composite cardiovascular events, and a total of 12 patients (27.9%) died. Kaplan-Meier survival curves showed a significantly lower cumulative survival rate for cardiovascular composite endpoint events (log-rank P=0.04) and all-cause death (log-rank P=0.04) in cluster 2 than in cluster 1. Univariate Cox proportional hazard regression model analysis showed that hATTR-CM patients with reduced estimated glomerular filtration rate, left ventricular ejection fraction≤40%, and moderate to severe mitral regurgitation were risk factors for vascular composite events (all P<0.05). Multivariate Cox proportional hazard regression analysis showed that left ventricular ejection fraction≤40% was an independent risk factor (P<0.01). Conclusions: Cluster analysis is a valuable prediction tool on the prognostic stratification of hATTR-CM. Cluster 2, which is late-onset with onset of heart failure symptoms has a worse prognosis during follow-up period. The occurrence of composite cardiovascular events in hATTR-CM is related to left ventricular ejection fraction≤40%. Cluster analysis is helpful for clinical identification of high-risk groups.

The systemic inflammation response index (SIRI) predicts survival in advanced non-small cell lung cancer patients undergoing immunotherapy and the construction of a nomogram model.

Inflammation and immune evasion are associated with tumorigenesis and progression. The Systemic Inflammation Response Index (SIRI) has been proposed as a pre-treatment peripheral blood biomarker. This study aims to compare the relationship between SIRI, various serum biomarkers, and the prognosis of NSCLC patients before and after treatment. A retrospective study was conducted on advanced NSCLC patients treated with anti-PD-1 drugs from December 2018 to September 2021. Peripheral blood markers were measured pre- and post-treatment, and hazard ratios were calculated to assess the association between serum biomarkers and progression-free survival (PFS) and overall survival (OS). Kaplan-Meier curves and Cox proportional hazards models were employed for survival analysis. A nomogram model was built based on multivariate Cox proportional hazards regression analysis using the R survival package, with internal validation via the bootstrap method (1,000 resamples). Predictive performance was expressed using the concordance index (C-index), and calibration plots illustrated predictive accuracy.The application value of the model was evaluated by decision curve analysis (DCA). Among 148 advanced NSCLC patients treated with PD-1 inhibitors, the median PFS was 12.9 months (range: 5.4-29.2 months), and the median OS was 19.9 months (range: 9.6-35.2 months). Univariate analysis identified pre- and post-treatment SIRI, mGRIm-Score, and PNI as independent prognostic factors for both PFS and OS (p < 0.05). Multivariate analysis demonstrated that high post-SIRI and post-mGRIm-Score independently predicted poor PFS (P < 0.001, P = 0.004) and OS (P = 0.048, P = 0.001). The C-index of the nomogram model for OS was 0.720 (95% CI: 0.693-0.747) and for PFS was 0.715 (95% CI: 0.690-0.740). Internal validation via bootstrap resampling (B = 1,000) showed good agreement between predicted and observed OS and PFS at 1, 2, and 3 years, as depicted by calibration plots. SIRI is an important independent predictor of early progression in advanced NSCLC patients treated with PD-1 inhibitors and may assist in identifying patients who will benefit from PD-1 inhibitors therapy in routine clinical practice.

Analysis of prognostic risk factors for patients with locally advanced gastric cancer in the stage ypT0~2N0M0 after neoadjuvant chemotherapy

Objectives: To analyze the long-term prognosis of patients with locally advanced gastric cancer in the stage of ypT0~2N0M0 after neoadjuvant chemotherapy. Methods: The clinical data of 78 patients with locally advanced gastric cancer who underwent neoadjuvant chemotherapy and radical resection at ypT0~2N0M0 stage from January 2012 to December 2019 in the Department of Abdominal Surgery/Pancreatic and Gastric Surgery of the Cancer Hospital of Chinese Academy of Medical Sciences were retrospectively analyzed. Kaplan-Meier method was used to calculate the overall survival and disease-free survival, and the survival difference between patients with postoperative ypT0N0M0 and ypT1~2N0M0 was compared. Multivariate Cox proportional hazards regression analysis was performed on clinical, pathologic and treatment measures that may affect survival. Results: Among the 78 patients, there were 18 cases (23.1%) with ypT0N0M0, 14 cases (17.9%) with ypT1aN0M0, 17 cases (21.8%) with ypT1bN0M0, and 29 cases (37.2%) with ypT2N0M0. Median follow-up time was 74.1 (19.8~132.5) months. Fourteen patients (17.9%) had tumor recurrence and metastasis, and 9 patients died from tumor recurrence and metastasis. The 5-year disease-free survival and overall survival rates were 84.4% and 87.8%, respectively. There was no statistically significant difference in 5-year overall survival (86.9% vs 87.8%) or 5-year disease-free survival (88.9% vs 83.2%) between patients with ypT0N0M0 and ypT1~2N0M0. Analysis of factors that may affect prognosis revealed that signet ring cell carcinoma, nerve invasion, and lymph node dissection of fewer than 16 were significantly associated with prognosis (P＜0.05). Multivariate Cox analysis including these three factors showed that only lymph node dissection of fewer than 16 was an independent risk factor affecting prognosis (OS: HR=10.44 ,95% CI: 2.15-50.72, P=0.004; DFS: HR=11.47, 95% CI: 2.85-46.20, P=0.001). Conclusions: The long-term prognosis of patients with locally advanced gastric cancer at ypT0~2N0M0 stage after neoadjuvant chemotherapy is relatively good, and the long-term survival time of patients with ypT1~2N0M0 and ypT0N0M0 is similar. Lymph node dissection of less than 16 nodes may be an independent risk factor affecting prognosis. During surgery, efforts should be made to increase the number of lymph node dissections. For patients with less than 16 nodes dissected, postoperative treatment and follow-up should be strengthened.

Construction and validation of a regulatory T cells-based classification of renal cell carcinoma: an integrated bioinformatic analysis and clinical cohort study.

Renal cell carcinoma (RCC), exhibiting remarkable heterogeneity, can be highly infiltrated by regulatory T cells (Tregs). However, the relationship between Treg and the heterogeneity of RCC remains to be explored. We acquired single-cell RNA-seq profiles and 537 bulk RNA-seq profiles of TCGA-KIRC cohort. Through clustering, monocle2 pseudotime and prognostic analyses, we identified Treg states-related prognostic genes (TSRPGs), then constructing the RCC Treg states-related prognostic classification (RCC-TSC). We also explored its prognostic significance and multi-omics landmarks. Additionally, we utilized correlation analysis to establish regulatory networks, and predicted candidate inhibitors. More importantly, in Xinhua cohort of 370 patients with kidney neoplasm, we used immunohistochemical (IHC) staining for classification, then employing statistical analyses including Chi-square tests and multivariate Cox proportional hazards regression analysis to explore its clinical relevance. We defined 44 TSRPGs in four different monocle states, and identified high immune infiltration RCC (HIRC, LAG3+, Mki67+) as the highly exhausted subtype with the worst prognosis in RCC-TSC (p < 0.001). BATF-LAG3-immune cells axis might be its underlying metastasis-related mechanism. Immunotherapy and inhibitors including sunitinib potentially conferred best therapeutic effects for HIRC. Furthermore, we successfully validated HIRC subtype as an independent prognostic factor within the Xinhua cohort (OS, HR = 16.68, 95% CI = 1.88-148.1, p = 0.011; PFS, HR = 4.43, 95% CI = 1.55-12.6, p = 0.005). Through integrated bioinformatics analysis and a large-sample retrospective clinical study, we successfully established RCC-TSC and a diagnostic kit, which could stratify RCC patients with different prognosis and to guide personalized treatment.

The correlation between uveal melanoma and iris nevus

PurposeTo investigate the impact of iris nevus on the incidence and prognosis of uveal melanoma (UM).MethodsA retrospective cohort study was conducted involving 1128 UM cases and 4356 healthy controls. Participants were categorized based on iris nevus presence and grade: grade 0 (no iris nevus), grade 1 (single iris nevus), grade 2 (multiple iris nevi), and grade 3 (partial or complete darkening of the iris). Propensity matching score method was employed to control for age and sex differences, while the χ 2 test was used to compare the existence rate and grade of iris nevus between groups. Univariate ANOVA evaluated differences among various iris nevus grades, the Kaplan–Meier method analyzed the prognosis of patients with different iris nevus grades, and multivariate Cox proportional risk regression analysis was conducted to evaluate the relationship between clinical data and prognosis.ResultsA total of 5484 subjects were analyzed. UM patients exhibited a higher prevalence and grade of iris nevus (all P < 0.001) after propensity matching. Patients with iris nevus in the affected eye did not show a worse prognosis (P = 0.414). However, those with partial or complete iris darkening or multiple nevi had a poorer prognosis compared to those with a single or no iris nevus (all P < 0.05). Iris nevus presence and grade in the healthy eye had no prognostic impact (P = 0.726 and P = 0.825, respectively). The multivariate COX proportional risk model showed that tumor diameter (P < 0.001), age (P = 0.020), and grade of iris nevus in the affected eye (P = 0.009) were independent risk factors for a worse prognosis. LSD analysis revealed that patients with partial or complete darkening of the iris had larger tumor diameters than those without iris nevus (P = 0.013), single nevus (P = 0.015), and multiple nevus (P = 0.023).DiscussionOur findings indicate a higher proportion and grade of iris nevus in UM patients compared to controls, and a worse prognosis for UM patients with higher-grade iris nevi in the affected eye.

Atherosclerotic plaque evolution predicts cerebral ischemic events in patients with intracranial atherosclerosis: a multicentre longitudinal study using high-resolution MRI.

Intracranial atherosclerosis (ICAS) is the leading cause of ischemic stroke in Asians and the recurrent rate remains high despite the optimal medical treatment. This study aimed to confirm that follow-up high-resolution magnetic resonance imaging (hrMRI) provided essential values in predicting subsequent cerebral ischemic events in patients with ICAS. Patients with moderate to severe stenosis in the middle cerebral artery (MCA) defined by magnetic resonance (MRA) or computed tomography angiography (CTA) were recruited from three centers retrospectively. Detailed plaque composition was analyzed on baseline and follow-up hrMRI. Multivariate Cox proportional hazards regression analysis was used to identify the key risk factors for predicting subsequent ischemic events. Among 152 patients, a total of 86 patients with MCA atherosclerotic stenosis underwent follow-up hrMRI exams and ipsilateral cerebral ischemic events occurred in 12 patients during a 1-year follow-up. Analyses showed the predictors of ischemic events were age (adjusted Hazard ratio (HR) = 0.942; 95% Confidence Interval (CI), [0.903, 0.983]; p = 0.006), progression of plaque burden (HR = 3.818; 95% CI [1.117, 13.051]; p = 0.033), vessel expansion (HR = 5.173; 95% CI [1.077, 24.838]; p = 0.040) and enhancement ratio progression (HR = 6.144; 95% CI [1.480, 25.511]; p = 0.012). The combined model achieved a concordance index of 0.804 (95% CI [0.658, 0.950]). Longitudinal hrMRI evaluation improved the accuracy in identifying higher-risk patients with intracranial atherosclerosis. Question Can longitude high-resolution magnetic resonance imaging (hrMRI) help clinicians observe intracranial plaque evolution? Findings Compared with the baseline exam, intracranial plaque evolution distinguished by follow-up hrMRI exam showed a higher accuracy in predicting subsequent ischemic events. Clinical relevance Longitudinal high-resolution magnetic resonance vessel wall imaging enables dynamic observation and evaluation of the changes in plaque characteristics among intracranial atherosclerosis patients. Atherosclerotic plaque evolution revealed by repeated exams can strengthen the risk stratification of patients with intracranial atherosclerosis.