Kaplan-Meier Analysis Research Articles

Aqueous Angiography Guided Bent Ab Interno Needle Goniectomy in High versus Low Aqueous Humor Outflow Regions in POAG: A Pilot RCT

Précis: Trabecular cutting minimally invasive glaucoma surgery like bent ab interno needle goniectomy (BANG) when performed in baseline aqueous angiography identified low aqueous humor outflow regions, results in greater success of intraocular pressure reduction. Purpose: To study the efficacy of Bent Ab Interno Needle Goniectomy (BANG) in high versus low aqueous humor outflow (AHO) regions as determined by Aqueous Angiography(AA) in patients with primary open angle glaucoma (POAG). Methods: A prospective, single-centre, pilot, randomized control trial recruited 30 eyes of 30 patients of POAG and visually significant cataract (45-80 y) and were randomised into two groups (“A”: BANG performed in the high-flow regions and “B”: BANG performed in the low-flow regions) of 15 each. AA was performed using indocyanine green dye (0.1%) to identify baseline high- and low-flow regions of the AHO pathways followed by BANG in these respective regions as per randomisation. Preoperative and postoperative data on IOP, number of antiglaucoma medications (AGMs) and any complications were noted over 6 months. Overall success was defined as achieving an IOP ≤15 mm Hg and ≥6 mm Hg at 6 months of follow-up with AGMs (qualified success) or without AGMs (complete success). Results: AA revealed high-flow regions of AHO pathways in the nasal quadrant and low-flow regions of AHO pathways in the temporal quadrant in all 30 patients. Both groups had comparable demographic composition [group A age: 65.3±6.48 y and male: female (14:1) and group B age: 64.6±7.08 y and male: female (13:2)]. The mean preoperative IOPs [group A (17.27±3.43 mm Hg); group B (17.60±5.42 mm Hg)] (P=0.842) and mean postoperative IOP at 6 months [group A (15.6±4.98 mm Hg); group B (13.13±2.29 mm Hg)] (P=0.09) were similar. However, lower qualified success was seen in group A (40.00%) compared to group B (86.67%; P=0.021). Survival in Kaplan-Meier analysis was higher in group B (P=0.021). Complications were comparable in both groups. Conclusion: Short-term results of BANG in low-flow AHO regions show enhanced success compared to those in high-flow AHO regions. This study suggests that trabecular cutting minimally invasive glaucoma surgeries (like BANG) may be performed in baseline low-flow AHO regions (temporal quadrant) instead of the high-flow AHO (nasal quadrant) regions.

Neurobrucellosis: a retrospective cohort of 106 patients

Abstract Background Neurobrucellosis, a serious central nervous system infection caused by Brucella species, presents significant challenges due to its diverse clinical manifestations and the risk of long-term complications and poor outcomes. Identifying predictors of adverse outcomes is critical for improving patient management and overall prognosis. Objectives This study aimed to evaluate the long-term morbidity and mortality associated with neurobrucellosis and to identify key predictors of adverse outcomes. Methods We performed a retrospective cohort study of 106 neurobrucellosis patients treated at two major referral centers in Mashhad, Iran, from March 21, 2011, to March 20, 2022. We analyzed clinical, neuroimaging, and laboratory data, and estimated survival probabilities using Kaplan–Meier analysis. Long-term morbidity was evaluated using the Glasgow Outcome Scale. Results The median age of the cohort was 30 years (IQR: 21.8–46.3). The median length of hospital stay was 11 days (IQR: 7–19.8), with an in-hospital mortality rate of 4.7% (n = 5). Survival probabilities were 92.2% (SE = 0.027) at 1 month and 90.1% (SE = 0.030) at 6 months. The median follow-up duration was 52 months (IQR: 35–77). At follow-up, 23.5% (n = 20) of patients had an unfavorable outcome based on the Glasgow Outcome Scale. Predictors of mortality included older age, altered level of consciousness, seizures, elevated body temperature on admission, and white matter changes on neuroimaging. Conclusion Neurobrucellosis is associated with significant long-term morbidity and mortality. Key predictors of mortality include older age, altered level of consciousness, seizures, elevated body temperature on admission, and white matter changes. Identifying these predictors can help in targeting therapeutic strategies and improving patient outcomes through early intervention and close monitoring.

Association of IL6 Gene Polymorphisms and Neurological Disorders: Insights from Integrated Bioinformatics and Meta-Analysis.

Interleukin 6 (IL6) is an inflammatory biomarker linked to central and peripheral nervous system diseases. This study combined bioinformatics and statistical meta-analysis to explore potential associations between IL6 gene variants (rs1800795, rs1800796, and rs1800797) and neurological disorders (NDs) and brain cancer. The meta-analysis was conducted on substantial case-control datasets and revealed a significant correlation between IL6 SNPs (rs1800795 and rs1800796) with overall NDs (p-value < 0.05). The disease-stratified analysis of rs1800795 revealed significant correlations with Schizophrenia, Alzheimer's, and Parkinson's diseases (p-value < 0.05), while rs1800796 showed a substantial connection with Celiac disease (p-value < 0.05). The ethnicity-stratified analysis revealed noteworthy associations between rs1800795 in both Asians and Caucasians (p-value < 0.05), while rs1800796 showed significant associations across all ethnic groups analyzed (p-value < 0.05). Furthermore, integrated Bioinformatics analyses using GTEx and TCGA datasets highlighted IL6's involvement in NDs and its potential role in brain cancer. Specifically, IL6 SNPs (rs1800795 and rs1800797) showed a significant association with Glioma (p-value < 0.001). Copy number alterations and increased IL6 expressions were linked to cancer severity (p-value < 0.001) and hypoxia (p-value < 0.0001). Kaplan-Meier survival analysis demonstrated that elevated IL6 expression was strongly associated with decreased overall survival in brain cancer patients (p-value < 0.0001). In conclusion, this study identified notable correlations between IL6 SNPs and NDs, underscoring their potential as valuable prognostic biomarkers for various neurological conditions.

RNA modification writer-based immunological profile and genomic landscape of tumor microenvironment in lung adenocarcinoma.

Recent studies have highlighted the role of RNA modification, that is, the dysregulation of epitranscriptomics, in tumorigenesis and progression. The potential for undoing epigenetic changes may develop novel therapeutic and prognostic approaches. However, the roles of these RNA modifications in the tumor microenvironment (TME) are still unknown. We assessed the expression properties and genetic alterations of 26 RNA modification writers, including adenosine-to-inosine RNA editing, alternative polyadenylation, m1A, and m6A in 502 lung adenocarcinoma (LUAD) samples from the Cancer Genome Atlas (TCGA) datasets. Then, we used differentially expressed gene (DEGs) to develop a signature for predicting patient outcomes, which was dubbed the "writer score" for RNA-modified writers. In addition, we analyzed the association between TME features, molecular subtypes, treatment sensitivity, and immunotherapy efficacy. We comprehensively evaluated the changes in multilayer RNA modification writers and identified the role of RNA modification writer expression imbalances in LUAD emergence and progression. Additionally, we constructed a risk-score model based on six LUAD prognosis-associated differentially expressed RNA modification writer genes. Kaplan-Meier (K-M) analyses revealed that the low risk-score signature had high overall patient survival. The predictive significance of the risk-score model was demonstrated using both univariate and multivariate Cox analyses. The risk-score model was positively correlated with the immune- and proliferation-related pathways. In response to anti-cancer treatment, high-risk score is related with high TMB, which has been discovered to correlate with immunotherapy effectiveness. This study showed a strong correlation between the TME variety, level of complexity, and the four types of RNA modification writers. In addition, this scoring system could potentially predict effective immunotherapy and deepens our understanding of TME characteristics.

Chronic kidney disease is a major risk factor for mortality in triglyceride deposit cardiomyovasculopathy patients.

Triglyceride deposit cardiomyovasculopathy (TGCV) is a rare cardiovascular disorder caused by defective intracellular lipolysis of triglyceride, resulting in heart failure and diffuse narrowing atherosclerosis. Recently, the registry of TGCV patients in Japan revealed that the 3-year overall survival rate was 80.1% and the 5-year overall survival rate was 71.8%. In this study, the effect on mortality of chronic kidney disease (CKD), diabetes malleus (DM), hypertension (HT), and dyslipidemia (DL) was analyzed using this retrospective registry of TGCV patients. The 3-year survival rate was 71.3% in the CKD group and 91.7% in the non-CKD group, and the 5-year survival rate was 61.8% in CKD group and 84.4% in the non-CKD group. The Kaplan-Meier analysis revealed that CKD is a risk factor for mortality in TGCV patients (p = 0.006). Although TGCV patients with CKD were older than those without CKD, Cox proportional hazard model analyses including age indicated that CKD has a significant association of the prognosis of TGCV patients (hazard ratio 2.33 [1.12-4.86], p = 0.024). DM, HT, and DL did not increase mortality in TGCV patients, although these risk factors were established in the general population. TGCV might cause cardiac disorders and kidney disease at the same time, because podocyte foot process disorder in the glomeruli might be caused by TGCV itself, while CKD should be a risk factor for mortality in TGCV patients as is true in the general population. In conclusion, CKD is a major risk factor for mortality in TGCV patients and thus should be paid attention to in these patients.

The prognostic value of systemic immune-inflammation index in patients with unresectable hepatocellular carcinoma treated with immune-based therapy

BackgroundPredicting the efficacy of immune-based therapy in patients with unresectable hepatocellular carcinoma (HCC) remains a clinical challenge. This study aims to evaluate the prognostic value of the systemic immune-inflammation index (SII) in forecasting treatment response and survival outcomes for HCC patients undergoing immune-based therapy.MethodsWe analyzed a cohort of 268 HCC patients treated with immune-based therapy from January 2019 to March 2023. A training cohort of 93 patients received atezolizumab plus bevacizumab (T + A), while a validation cohort of 175 patients underwent treatment with tyrosine kinase inhibitors (TKIs) combined with anti-PD-(L)1 therapy. The SII cutoff value, determined using X-tile analysis based on overall survival (OS) in the training cohort, divided patients into high (> 752*109) and low (≤ 752*109) SII groups. Prognostic factors were identified through univariate and multivariate logistic and Cox regression analyses, and survival outcomes were assessed using Kaplan–Meier methods. The predictive accuracy of SII was evaluated using receiver operating characteristic (ROC) curves.ResultsAn optimal SII cutoff of 752*109 stratified patients into high and low SII groups. Univariate and multivariate logistic regression indicated that SII was a significant predictor of the objective response rate (ORR), which was markedly different between the low and high SII subgroups (34.72% vs. 9.52%, P = 0.019). This finding was consistent in the validation cohort (34.09% vs. 16.28%, P = 0.026). SII also demonstrated prognostic value in Cox regression and Kaplan–Meier analyses. ROC curves confirmed that SII had superior predictive accuracy compared to common clinical indicators, with predictive relevance even in AFP-negative patients. Furthermore, a lower SII was associated with a higher T cell ratio and an increased number of CD8+ T cells and Granzyme B+ CD8+ T cells in peripheral blood.ConclusionSII is a promising predictor of both therapeutic efficacy and prognosis in HCC patients undergoing immune-based treatments. Its application may enhance clinical decision-making, thereby improving patient outcomes from immune-based therapy.

Trends of alkaline phosphatase to prealbumin ratio in patients with hepatitis B linked to hepatocellular carcinoma development.

Chronic hepatitis B often progresses silently toward hepatocellular carcinoma (HCC), a leading cause of mortality worldwide. Early detection of HCC is crucial, yet challenging. To investigate the role of dynamic changes in alkaline phosphatase to prealbumin ratio (APR) in hepatitis B progression to HCC. Data from 4843 patients with hepatitis B (January 2015 to January 2024) were analyzed. HCC incidence rates in males and females were compared using the log-rank test. Data were evaluated using Kaplan-Meier analysis. The Linear Mixed-Effects Model was applied to track the fluctuation of APR levels over time. Furthermore, Joint Modeling of Longitudinal and Survival data was employed to investigate the temporal relationship between APR and HCC risk. The incidence of HCC was higher in males. To ensure the model's normality assumption, this study applied a logarithmic transformation to APR, yielding ratio. Ratio levels were higher in females (t = 5.26, P < 0.01). A 1-unit increase in ratio correlated with a 2.005-fold higher risk of HCC in males (95%CI: 1.653-2.431) and a 2.273-fold higher risk in females (95%CI: 1.620-3.190). Males are more prone to HCC, while females have higher APR levels. Despite no baseline APR link, rising APR indicates a higher HCC risk.

Impact of ISUP grade group on cancer-specific mortality in radical prostatectomy-treated prostate cancer patients with organ-confined disease

Introduction: We aimed to test the impact of International Society of Urological Pathology (ISUP) grade group (GG) on cancer-specific mortality (CSM) in organ-confined (pT2) prostate cancer (PCa) at radical prostatectomy (RP). Methods: RP organ-confined prostate cancer (PCa) patients were identified (Surveillance, Epidemiology, and End Results 2004−2015). Cancer-specific survival (CSS) rates were tested in Kaplan-Meier plots and multivariable Cox regression (MCR) models according to GG: 1–3 vs. 4 vs. 5. Sensitivity analyses addressed GG4 and GG5 patients with available primary and secondary Gleason score (GS). Results: Overall, 61 172 patients with RP organ-confined PCa were identified. Of these, 57 715 (94.4%), 2036 (3.3%) and 1421 (2.3%) harbored GG1–3, 4, and 5, respectively. In Kaplan-Meier analyses, seven-years’ CSS estimates were 99.6 vs. 98.2 vs. 93.8% for GG1–3 vs. 4 vs. 5, respectively (p&lt;0.001). In MCR models, GG4 (hazard ratio [HR] 2.72, p&lt;0.001) and 5 (HR 9.95, p&lt;0.001) independently predicted higher CSM, relative to GG1–3. Furthermore, GG5 also independently predicted higher CSM (HR 3.72, p&lt;0.001) vs. GG4. In sensitivity analyses, 1.2, 1.6, and 2.4 CSM events per 1000 person-years of followup were respectively recorded for GS 4+4, 3+5, and 5+3 patients. Conversely, 4.8 vs. 5.3 CSM events per 1000 person-years of followup were respectively recorded for GS 4+5 vs. 5+4/5+5 patients. Conclusions: In organ-confined PCa, at RP, a small proportion of patients harbor GG4–5. These patients exhibit higher CSM than their GG1–3 counterparts. Moreover, detectable mortality rate differences indicate a dose-response effect according to primary and secondary GS. This phenomenon applies in both GG4 and GG5, as well as between GG4 and GG5.

Breast Conservation Surgery for Breast Cancer in Men.

Male breast cancer (MBC) is a rare disease, accounting for 1% of all breast cancers diagnosed in the United States. The rarity of MBC has limited the development of treatment algorithms specific to men. Thus, the standard of care has been mastectomy. The safety and feasibility of breast-conserving surgery (BCS) in MBC are unclear. This study assessed whether overall survival outcomes, local recurrence, and postoperative complications differed between MBC patients who underwent conservative surgery or mastectomy. A retrospective search for men aged ≥18 years diagnosed with breast cancer was conducted using the TriNetX network. Cohort 1 included patients who underwent BCS. Cohort 2 included patients who underwent mastectomy. Propensity score matching was conducted using age, BMI, tobacco use, cancer stage and tumor size (T1-T4), radiation, chemotherapy, hormonal therapy, genetics, and comorbidities. Outcomes of interest were 5-year overall survival (OS), local recurrence (LR), and postoperative complications. 423 patients underwent BCS, and 1,101 patients underwent mastectomy. After matching, 401 patients per cohort were identified. There was no difference in 5-year OS with the Kaplan-Meier analysis (Cohort 1: 84% vs Cohort 2: 86%, log-rank test p=0.412) or with LR (11% vs 13%, p=0.384). The mastectomy cohort was more likely to have postoperative complications, with a risk of 24% compared with 17% in the BCS cohort (p=0.011). There is no difference in the 5-year OS and LR rate between MBC patients who undergo BCS or mastectomy. The postoperative complication rate was higher with mastectomies. We conclude that BCS for unicentric male breast cancer is feasible and preferred for T1 and T2 cancers.

Time to neonatal mortality and its predictors among preterm neonates admitted to the neonatal intensive care unit in northern Ethiopia, 2023/2024: a retrospective cohort study

BackgroundA preterm neonate is defined by the World Health Organization as a child delivered before 37 weeks of gestation. In low- and middle-income countries, including Ethiopia, preterm-related complications are serious health problems due to increases in the mortality and morbidity of newborns and children under 5 years of age. The aim of this study was to assess the time to neonatal mortality and its predictors among preterm neonates admitted to the neonatal intensive care unit in northern Ethiopia, 2023/2024.MethodsAn institution-based retrospective cohort study was conducted among 495 randomly selected preterm neonates in six out of the fourteen general hospitals of Tigray, Ethiopia from October 2023 to June 2024. Epi Data version 4.6 and STATA version 14 were used for data entry and analysis, respectively. Descriptive statistics were carried out to determine the distribution. Kaplan-Meier analysis, life table, and log rank were computed. Cox proportional hazards models were fitted to identify independent predictors of preterm mortality.ResultsThe proportion of preterm neonatal mortality was 109 (22.7%). The overall median survival time was 21 (95% CI: 20, 28) days. Initiation of breast milk (AHR = 0.38 (95% CI: 0.24, 0.61)), respiratory distress syndrome (AHR = 1.9 (95% CI: 1.07,3.63)), perinatal asphyxia (AHR = 2.05 (95% CI: 1.05, 4.00)), receiving kangaroo mother care practice (AHR = 0.5 (95% CI: 0.34, 0.83)), and gestational age (AHR = 1.6 (95% CI 1.07, 2.59) were the predictors of time to death.ConclusionRespiratory distress syndrome, gestational age less than 32 weeks, and perinatal asphyxia at admission were found to be independent risk factors for preterm neonatal mortality. Breastfeeding and receiving kangaroo-mother care were independent preventive predictors of preterm neonatal mortality. It is better to give full emphasis and close follow-up to preterm neonates, especially during the early neonatal period.

Plasma Humanin and Non-Coding RNAs as Biomarkers of Endothelial Dysfunction in Rheumatoid Arthritis: A Pilot Study

Background: Rheumatoid arthritis (RA) is a chronic autoimmune disorder associated with an increased risk of cardiovascular disease (CVD), largely driven by peripheral endothelial dysfunction (ED). Humanin, a mitochondrial-derived peptide, has been suggested to play a protective role in endothelial function. However, the relationship between Humanin levels and ED in RA, as well as the interaction between Humanin and non-coding RNAs such as Long Non-Coding RNA GAS5, microRNA-21 (miR-21), and microRNA-103 (miR-103), remains unclear. Objective: This study aimed to investigate the relationship between circulating Humanin levels, non-coding RNAs (GAS5, miR-21, miR-103), and endothelial dysfunction (ED) in patients with RA. Additionally, we explored the correlation between Humanin expression and specific non-coding RNAs (GAS5, miR-21, and miR-103) to better understand their potential role in vascular health. Methods: Peripheral ED was assessed using flow-mediated pulse amplitude tonometry, with Ln-RHI values &lt;0.51 indicating dysfunction. Humanin levels, GAS5, miR-21, and miR-103 were measured in RA patients. Univariate and multivariate analyses were conducted to determine the relationship between these biomarkers and ED. Kaplan–Meier survival analysis and ROC curve analysis were used to assess the prognostic value of Humanin. Results: Higher Humanin levels were significantly associated with better endothelial function (OR = 0.9774, p = 0.0196). Kaplan–Meier analysis demonstrated that higher Humanin levels correlated with improved survival (p &lt; 0.0001). The non-coding RNAs (GAS5, miR-21, and miR-103) did not show significant associations with ED. Conclusions: Humanin is a potential protective biomarker for endothelial dysfunction and survival in RA patients. Further research is needed to explore the interaction between Humanin and non-coding RNAs in the context of vascular health.

Adjustment of the Framingham index by abdominal aortic calcification scores enables a more accurate prediction of long-term cardiac events in general population aged 40 years and above: evidence from NHANES 2013–2014

BackgroundAbdominal aortic calcification (AAC) is considered as a strong predictor of cardiovascular disease (CVD) events. Our study aimed to investigate whether the predicted risk for cardiac death with the Framingham risk score (FRS) could be further improved with the addition of AAC score in general population aged ≥ 40 years.MethodsA total of 2971 participants aged ≥ 40 years in the National Health and Nutrition Examination Surveys (NHANES) 2013–2014 were followed up. The Spearman’s rank correlation was performed to explore the correlation between the AAC score and FRS. the Kaplan-Meier method was used to make cumulative cardiac death curve. Predictors of cardiac death was identified by multivariate Cox regression. Additionally, the predictive value of FRS alone and combined with AAC score was estimated by comparing the area under the receiver-operating characteristic (ROC) curve (AUC) and calculating Integrated Discrimination Improvement (IDI).ResultsDuring a median of 70.50 months (interquartile range 58.43–82.57 months), 49 (1.649%) experienced cardiac death in the follow-up. The FRS was positively associated with AAC score. Both FRS and AAC score were independent predictors of cardiac death (hazard ratio 1.216; 95%CI 1.135 to 1.302; p < 0.00001; 1.159; 95%CI 1.109 to 1.211; p < 0.00001; respectively). Furthermore, Kaplan-Meier analysis demonstrated increased risk of cardiac death with increasing AAC score (log-rank 54.548, p<0.0001). The predictive value of FRS significantly was improved by adding with AAC score [increase in AUC from 0.734 to 0.780, p < 0.0001; IDI = 0.007, p = 0.013 ].ConclusionsAAC score is positively related with Framingham index, and FBS adjusted by AAC score further improved the prediction risk for cardiac death in general population aged ≥ 40 years.

Elevated Interleukin-6 Is Associated with an Increased Risk of Long-Term Arteriovenous Fistula Failure for Dialysis

Background/Objectives: The autologous arteriovenous fistula (AVF) is the preferred choice for vascular access in patients with end-stage kidney disease (ESKD) undergoing maintenance hemodialysis. However, in the long term, the primary patency of AVF is suboptimal, with an AVF failure of approximately 30% in one year. The aim of this study is to examine how the pre-operative baseline levels of interleukin-6 (IL-6) affect long-term AVF failure. Methods: This retrospective, observational study involves ESKD patients admitted to the Vascular Surgery Clinic for AVF creation from January 2020 to December 2023. Ultimately, a total of 91 patients whose AVFs matured and began dialysis were enrolled. Prior to surgery, each patient underwent a thorough blood sample collection, with IL-6 levels assessed. The patients were categorized into two groups: those with functioning AVFs and those with dysfunctional AVFs. Their progress was monitored via a review of medical records, telephone interviews, or direct contact. Following the surgery, patients were observed for an average of 1.53 ± 0.94 years. Results: During the follow-up, patients who experienced AVF failure had a higher incidence of diabetes mellitus (p = 0.019) and active smoking (p = 0.012), as well as higher levels of IL-6 (p &lt; 0.001). At ROC analysis, we found a strong association between IL-6 value and AVF failure (AUC: 0.814, p &lt; 0.001), with an optimal cut-off value of 7.08 (76.5% Sensitivity and 79.7% Specificity). Furthermore, at the survival curve Kaplan-Meier analysis, we observed a higher occurrence of AVF failure in patients with baseline IL-6 values above the median (p = 0.004), in tertile 3 (p = 0.002), and above the optimal cut-off value (p &lt; 0.001). At cox-regression analysis, elevated baseline IL-6 levels are associated with AVF Failure (HR: 2.23, p &lt; 0.001). Conclusions: In the current study, we demonstrated that elevated IL-6 levels at baseline are associated with long-term AVF failure, independent of age, sex, and cardiovascular risk factors.

Impact of Warfarin and Dual Antiplatelet Therapy on Graft Failure After Coronary Endarterectomy: A Retrospective Cohort Study.

Coronary endarterectomy combined with coronary artery bypass grafting (CE-CABG) effectively achieves coronary revascularization in patients with diffuse atherosclerotic coronary artery disease (CAD). However, the loss of the subendothelial tissue at the CE-CABG coronary artery accelerates local thrombosis, leading to CE-CABG graft failure. Dual antiplatelet therapy (DAT) and warfarin plus aspirin (WPA) are the two most common anticoagulation strategies post CE-CABG. This retrospective study compares the clinical outcomes and graft failure rates associated with these two approaches. This study is a retrospective cohort study. Between July 2016 and April 2024, 102 patients with diffuse CAD underwent CE-CABG. Six patients were excluded. In total, 96 patients (mean age 59.8 ± 7.7years) enrolled in the study (43 in DAT group and 53 in WPA group). The DAT group received aspirin (100mg, qd) and clopidogrel (75mg, qd) for 1 year postoperatively, transitioning to aspirin (100mg, qd) after 1 year. The WPA group received warfarin (international normalized ratio, INR remained at 1.8-2.5) and aspirin (100mg, qd) for 3 months postoperatively, followed by DAT after 3 months, changed to aspirin monotherapy after 1year. The primary endpoint was graft failure of the CE-CABG graft. Four patients died during the perioperative period (1 in DAT group, 3 in WPA group), resulting in an overall perioperative mortality rate of 4.2%. Five patients were lost for follow-up. Mean follow-up time was 38months. Three patients died during the follow-up period (1 in DAT group, 2 in WPA group). The CE-CABG graft patency of the WPA group was significantly higher compared to the DAT group (88.1% vs. 50.0%, P < 0.001). Kaplan-Meier analysis showed that the median graft failure time was significantly longer in the WPA group (77months, 95% CI 69-85) compared to the DAT group (73months, 95% CI 17-129, P = 0.017). A higher proportion of the DAT group was classified as NYHA III-IV compared to the WPA group (26.2% vs. 10.2%, P = 0.046). One patient of the WPA group had a gastrointestinal bleeding event, and the overall incidence of bleeding events was not statistically different between the two groups. Using the WPA strategy after CE-CABG significantly reduces the rate of graft failure and improves cardiac function without increasing the risk of bleeding events.

Pulmonary Hemodynamic Correlates and Prognostic Value of the Cardiopulmonary Exercise Score in Patients With Left Heart Failure

Abstract Objective: Pulmonary hypertension secondary to left heart failure is associated with an abnormal response to exercise and poor prognosis. The objective of this study is to develop an algorithm by using data from cardiopulmonary exercise testing (CPET) to assess the severity of pulmonary hemodynamics and predict clinical worsening and mortality in patients with heart failure. Methods: From April 2017 to December 2018, a total of 102 patients with heart failure who underwent CPET and invasive right heart catheterization participated in this prospective study. All enrolled patients had their clinical characteristics, hemodynamic parameters, and CPET results. Based on the CPET data namely peak oxygen uptake, the minute ventilation/carbon dioxide production slope, resting end-tidal carbon dioxide, oxygen uptake/work rate flattening, exercise oscillatory ventilation, and oxygen uptake efficiency slope, a Heart Failure Cardiopulmonary Exercise (HFCE) score was developed. The total score was then calculated to categorize patients into 3 groups: low score (0–3) (n = 31), intermediate score (4–7) (n = 45), and high score (8–14) (n = 26). Clinical events were defined as all-cause death and rehospitalization for heart failure, which were recorded and tracked for at least 12 months. Pearson’s correlation coefficients were calculated to assess the relationship between the HFCE score and hemodynamic parameters, 6-minute walk distance, and N-terminal-pro hormone brain natriuretic peptide. Cox proportional hazards regression analysis was used to identify independent predictors of clinical events. Survival curves for clinical events were generated using the Kaplan-Meier method and compared among the 3 groups with different HFCE scores with a log-rank test. Results: The high HFCE score group had a higher prevalence of New York Heart Association class Ⅲ–Ⅳ (high score vs. intermediate score vs. low score: 85% (22/26) vs. 56% (25/45) vs. 45% (14/31), P = 0.008), higher N-terminal-pro hormone brain natriuretic peptide levels (high score vs. intermediate score vs. low score: (3,039 ± 2,171) ng/L vs. (2,039 ± 2,353) ng/L vs. (1,438 ± 947) ng/L, P = 0.035), lower 6-minute walk distance (high score vs. intermediate score vs. low score: (312 ± 79) m vs. (362 ± 84) m vs. (363 ± 76) m, P = 0.042) compared to intermediate score or low score. The high HFCE score correlated well with high levels of pulmonary vascular resistance (r = 0.539, P &lt; 0.01), pulmonary artery wedge pressure (r = 0.292, P &lt; 0.01), and mean pulmonary artery pressure (r = 0.474, P &lt; 0.01), as well as low levels of cardiac output (r = –0.357, P &lt; 0.01). Moreover, 46 patients developed composed clinical events at 12 months. In the multivariate model, the HFCE score was an independent predictor of composed clinical events (hazard ratio = 1.142, 95% confidence interval: 1.041–1.253, P = 0.005). Kaplan-Meier analysis showed a significantly higher probability of composed clinical events in patients with a higher HFCE score (P log-rank = 0.004). Conclusion: The HFCE score—obtained through CPET—provides valuable prognostic information by indicating the severity of hemodynamics in patients with pulmonary hypertension secondary to left heart failure. It can likely serve as a reliable predictor for clinical worsening and mortality.

Six-Month Outcomes in the Long-Term Outcomes After the Multisystem Inflammatory Syndrome in Children Study.

Multisystem inflammatory syndrome in children (MIS-C) is a life-threatening complication of COVID-19 infection. Data on midterm outcomes are limited. To characterize the frequency and time course of cardiac dysfunction (left ventricular ejection fraction [LVEF] <55%), coronary artery aneurysms (z score ≥2.5), and noncardiac involvement through 6 months after MIS-C. This cohort study enrolled participants between March 2020 and January 2022 with a follow-up period of 2 years. Participants were recruited from 32 North American pediatric hospitals, and all participants met the 2020 Centers for Disease Control and Prevention case definition of MIS-C. MIS-C after COVID-19 infection. Outcomes included echocardiography core laboratory (ECL) assessments of LVEF and maximum coronary artery z scores (zMax); data collection on cardiac and noncardiac sequelae during hospitalization and at 2 weeks, 6 weeks, and 6 months after discharge; and age-appropriate Patient-Reported Outcomes Measurement Information Systems (PROMIS) Global Health Instruments at follow-up. Descriptive statistics, linear regression models, and Kaplan-Meier analysis were used. Of 1204 participants (median [IQR] age, 9.1 [5.6-12.7] years; 724 male [60.1%]), 325 self-identified with non-Hispanic Black race (27.0%) and 324 with Hispanic ethnicity (26.9%). A total of 548 of 1195 participants (45.9%) required vasoactive support, 17 of 1195 (1.4%) required extracorporeal membrane oxygenation, and 3 (0.3%) died during hospitalization. Of participants with echocardiograms reviewed by the ECL (n = 349 due to budget constraints), 131 of 322 (42.3%) had LVEF less than 55% during hospitalization; of those with follow-up, all but 1 normalized by 6 months. Black race (vs other/unknown race), higher C-reactive protein level, and abnormal troponin level were associated with lowest LVEF (estimate [SE], -3.09 [0.98]; R2 = 0.14; P =.002). Fifteen participants had coronary artery z scores of 2.5 or greater at any time point; 1 participant had a large/giant aneurysm. Of the 13 participants with z scores of 2.5 or greater during hospitalization, 12 (92.3%) had normalized by 6 months. Return to greater than 90% of pre-MIS-C health status (energy, sleep, appetite, cognition, and mood) was reported by 711 of 824 participants (86.3%) at 2 weeks, increasing to 548 of 576 (95.1%) at 6 months. Fatigue was the most common symptom reported at 2 weeks (141 of 889 [15.9%]), falling to 3.4% (22 of 638) by 6 months. PROMIS Global Health parent/guardian proxy median T scores for fatigue, global health, and pain interference improved significantly from 2 weeks to 6 months (fatigue, 56.1 vs 48.9; global health, 48.8 vs 51.3; pain interference, 53.0 vs 43.3; P < .001) and by the 6-week visit were at least equivalent to prepandemic population norms. Results of this cohort study suggest that although children and young adults with MIS-C can have severe disease during the acute phase, most recovered quickly and had a reassuring midterm prognosis.

Mfsd2a suppresses colorectal cancer progression and liver metastasis via the S100A14/STAT3 axis

BackgroundColorectal cancer (CRC) exhibits a high incidence globally, with the liver being the most common site of distant metastasis. At the time of diagnosis, 20–30% of CRC patients already present with liver metastases. Colorectal liver metastasis (CRLM) is a major cause of mortality among CRC patients. The pathogenesis of CRLM involves complex molecular mechanisms and the hepatic immune microenvironment, but current clinical prevention and treatment are significantly limited. Recent studies have revealed that the major facilitator superfamily domain containing protein-2a (Mfsd2a) plays a pivotal role in the development and metastasis of various cancers. For instance, Mfsd2a inhibits gastric cancer initiation and progression and may impact angiogenesis. However, the mechanisms by which Mfsd2a influences CRC progression and liver metastasis remain unclear.MethodsIn this study, we conducted a survival analysis of Mfsd2a in colorectal cancer using data from the GEPIA and GEO databases, and examined the expression differences between primary tumor (PT) and liver metastasis (LM). We further assessed the clinical significance and prognostic relevance of Mfsd2a through immunohistochemical analysis of tissue samples from 70 CRLM patients. Moreover, Kaplan-Meier analysis was used to perform survival analysis on these patients. The biological function of Mfsd2a in CRLM was confirmed by a series of experiments conducted both in vitro and in vivo. Additionally, we investigated downstream molecular pathways using western blot, Co-immunoprecipitation, immunofluorescence, and mass spectrometry techniques.ResultsWe observed that Mfsd2a expression is reduced in LM compared to PT, and higher Mfsd2a levels are associated with better prognosis in CRLM patients. Furthermore, function assays demonstrated that Mfsd2a suppresses CRC cells proliferation, migration, invasion, and EMT in vitro, while also delaying tumor growth and liver metastasis in vivo. Mechanistically, Mfsd2a interacts with S100A14, enhancing its expression and inhibiting phosphorylation of STAT3. In addition, the STAT3 activator colivelin partially reversed the inhibitory effect of Mfsd2a overexpression on the progression of colorectal cancer and liver metastasis.ConclusionIn summary, Mfsd2a inhibits colorectal cancer progression and liver metastasis by interacting with S100A14, thereby suppressing the phosphorylation of STAT3. Mfsd2a functions as a tumor suppressor in CRLM and could be a promising therapeutic target for treating CRC patients with liver metastasis.Graphical abstract

Pro-adrenomedullin as an independent predictive biomarker for heart failure in atrial fibrillation and flutter.

This study aimed to investigate potential biomarkers for predicting incident heart failure (HF) in patients with atrial fibrillation and flutter (AF and AFL), utilizing proteomic data from the UK Biobank Pharma Proteomics Project (UKB-PPP). This study analysed data from AF and AFL patients, split into discovery (n=1050) and replication (n=305) cohorts. Plasma biomarkers were screened using a multivariable-adjusted Cox proportional hazards model. Kaplan-Meier survival analysis and area under the receiver operating characteristic (ROC) curve assessments were conducted to evaluate predictive performance. Over a follow-up of 14.2years, 222 cases (21.1%) of HF were documented in the discovery cohort, while 117 cases (38.4%) occurred over 13.8years in the replication cohort. Out of 2923 proteins measured, only pro-adrenomedullin (pro-ADM) consistently showed a significant association with incident HF in both cohorts. In the discovery cohort, each unit increase in pro-ADM was linked to an increased risk of HF (HR=2.78, 95% CI 1.64-4.71, P<0.001, FDR=0.026), which was confirmed in the replication cohort (HR=3.95, 95% CI 1.97-7.94, P<0.001, FDR=0.012). Kaplan-Meier analysis demonstrated that patients with higher pro-ADM levels had significantly shorter time to HF onset, with median times ranging from 2306 to 3183days across quartiles (P<0.001). The cumulative incidence of HF ranged from 15.3% to 42.7% across quartiles of pro-ADM (log-rank P<0.001). Adding pro-ADM to a model with traditional risk factors, including NT-proBNP, significantly improved predictive accuracy for 3-year (AUC=0.783; integrated discrimination improvement [IDI]=0.010 and net reclassification index [NRI]=0.206, both P=0.002) and 5-year (AUC=0.749, IDI=0.013, NRI=0.179, P=0.001) risk of HF. In sensitivity analyses, the association between pro-ADM and incident HF remained consistent after excluding participants with self-reported AF and AFL, with each unit increase in pro-ADM being associated with an increased risk of HF (HR=1.77, 95% CI 1.02-3.04, P=0.041) and across subgroups of paroxysmal AF (HR=2.80, 95% CI 1.11-7.07, P=0.029) and persistent AF (HR=4.36, 95% CI 1.41-13.43, P=0.010). Pro-ADM is identified as an independent biomarker for predicting incident HF in AF and AFL patients. Its inclusion in risk prediction models enhances the ability to stratify HF risk beyond traditional biomarkers, demonstrating its potential utility in clinical practice.

Triglyceride-glucose index: carotid intima-media thickness and cardiovascular risk in a European population

BackgroundThe triglyceride-glucose (TyG) index is now widely recognized as a marker of insulin resistance and has been linked to the development and prognosis of atherosclerotic cardiovascular diseases (ASCVD) in numerous populations, particularly in the Eastern world. Although there are fewer reports from the Western world, and they are sometimes contradictory, the absence of definitive data on the relationship between a raised TyG index and cardiovascular risk suggested the opportunity of testing this biochemical marker against a well-established vascular marker such as the carotid intima media thickness (c-IMT).MethodsPrimary prevention patients were selected from a cohort of individuals who underwent c-IMT measurement between 1984 and 2018 at the Dyslipidemia Center at the ASST Grande Ospedale Metropolitano Niguarda in Milan, Italy. The TyG index was calculated as the Ln [fasting TG (mg/dL)×fasting glucose (mg/dL)/2]. Carotid ultrasonography was performed using echographic measurements of the far walls of the left and right common, internal carotids, and bifurcations. Patients were followed for up to 20 years with periodic evaluation of biochemical parameters. ASCVD events were monitored through hospital records, where all patients were regularly examined.ResultsThe analysis included 3108 individuals with a mean age of 54.9 ± 13.1 years. Participants were generally non-obese, with an average BMI of 24.6 ± 3.5 Kg/m2. Among the women, 83.1% were postmenopausal. The mean TyG index was 8.65 ± 0.59. There was a significant association between the TyG index and all c-IMT measurements. Those in the highest TyG index quartiles had significantly higher IMTmean and IMTmax compared to those in the lower quartiles. These associations were consistent across all vascular sites examined and remained significant after adjusting for all potential confounders. Kaplan-Meier survival analysis revealed an increased incidence of ASCVD events in the two highest TyG index quartiles.ConclusionsTyG index is a sensitive marker of risk in a European population with moderate ASCVD risk, as assessed by c-IMT measurements, in a large cohort of Lipid Clinic patients.

Sequence of Chemotherapy May Not Impact Survival After Resection of Pancreatic Tail Adenocarcinoma.

Pancreatic ductal adenocarcinoma (PDAC) of the body/tail is notably different than PDAC in the head of the pancreas. Surgery plus chemotherapy is known to improve outcomes for all PDAC. The sequence of this therapy is well studied in head cancers yet has never been evaluated systematically in relation to distal pancreatectomy (DP). Patients receiving DP for PDAC and who received chemotherapy were included. Patients were compared receiving neoadjuvant systemic therapy (NAST) only, adjuvant (AST) only, both NAST + AST, and who received total neoadjuvant therapy (TNT), defined as > 24 weeks NAST before DP. PSM was performed 1:1 between AST and each other group creating quadruplets of patients for analysis. Matching factors were determined by multivariate cox-regression analysis of factors independently affecting survival. Survival was considered from diagnosis and from surgery to account for potential biases. In total, 4677 patients were selected with 400 (8.6%) receiving TNT, 536 (11.5%) NAST, 3235 (69.2%) AST, and 506 (10.8%) NAST + AST. A total of 341 quadruplets were selected after PSM. There were no differences in comorbidities, T/N-stage, retrieved or positive lymph nodes, and margin status after matching. Kaplan-Meier analysis showed no difference in median OS between the matched treatment groups (33.71 ± 2.07 vs. 35.22 ± 1.62 vs. 32.53 ± 3.31 vs. 37.88 ± 1.90, respectively; log-rank p = 0.464). Five-year OS was not different between the groups (21% vs. 18% vs. 20% vs. 25%, respectively; p = 0.501). The sequence of chemotherapy and surgery did not impact survival in distal PDAC. Providers should tailor an individualized approach designed to maximize the chance of completing both treatments.