Kaplan-Meier Survival Analysis Research Articles

Outcomes of Device Extraction in Patients with Chronic Kidney Disease on Renal Replacement Therapy and Cardiac Implantable Electronic Device Infections

BackgroundPatients with chronic kidney disease (CKD) on renal replacement therapy (RRT) are at high risk for cardiovascular implantable electronic device (CIED) infections. Although device extraction is standard management, it is often avoided in these patients due to high procedural risks. ObjectivesEvaluate the outcomes of CIED extraction in CKD on RRT patients with device infection. MethodsThis study utilized data from the TriNetX research network. The International Classification of Diseases-10th Revision-Clinical Modification coding system was used to identify patients. Adults with a history of CKD on RRT and CIED infection were included. Patients with renal transplantation and prosthetic heart valves were excluded. Patients were stratified by device extraction. The primary outcome was mortality at one year. ResultsA total of 530 patients were identified, of whom 30% (n=159) underwent device extraction. Following propensity score matching (PSM), 302 patients remained, with 151 in each group. Kaplan-Meier survival analysis demonstrated a significant one-year survival benefit for patients in the device extraction group (59.2%) compared to the no-extraction group (48.8%, p=0.043, HR 0.696, 95% CI 0.489-0.991). Freedom from complications such as pericardial effusion was similar between groups. Sensitivity analysis using Cox proportional hazards, adjusted for baseline confounders, confirmed the survival benefit of extraction, with a reduced mortality risk (HR 0.581, 95% CI 0.382-0.883, p=0.011)." ConclusionIn CKD on RRT patients with CIED infection, device extraction is associated with a reduction in all-cause mortality at one year. However, the rate of device extraction is low in this group.

The Association Between Body Mass Index and 28-day Mortality in Patients With Sepsis: A Retrospective Cohort Study.

Sepsis is a severe clinical syndrome with high morbidity and mortality in intensive care units (ICUs). Body Mass Index (BMI) shows a rising trend of obese patients being admitted to ICUs. The relationship between BMI and the clinical outcome of sepsis remains highly debated. The data used in this study were sourced from the Intensive Care Information Center IV (MIMIC-IV) database. Baseline information extracted within 24 hours of ICU admission was categorized according to World Health Organization (WHO)'s BMI classifications. A multivariate Cox regression model and curve fitting assessed the independent correlation between BMI and the primary outcome. A total of 7836 patients were included in the study and categorized into five groups based on BMI. The overall 28-day mortality rate was 21.94% (1719/7836). Class I obesity (17.14%) and class II/III obesity (13.49%) individuals tended to be younger and male. Compared to patients with normal BMI (32.55%), those with low BMI (5.79%) had a 47% increased risk of 28-day mortality (HR 1.47, 95% CI 1.16-1.85, P = 0.0013), while class II/III obesity patients had a 17% lower 28-day mortality rate (HR 0.83, 95% CI 0.71-0.97, P = 0.0218). Curve fitting revealed a nonlinear relationship between BMI and 28-day mortality. The Kaplan-Meier survival analysis highlighted variations in survival rates across the five groups (P = 0.0123), with underweight patients exhibiting poorer survival outcomes. In sepsis patients, a low BMI is related to higher 28-day mortality compared to those with a normal BMI. Conversely, patients with a BMI≥35kg/m2 have significantly reduced mortality risks.

Does the Combination of Metabolic Syndrome and Low Fat-Free Mass Shorten an Individual's Disability-Free Life? A 12-Year Prospective Cohort Study of the Korean Genome and Epidemiology Study (KoGES).

This study aims to explore the combined risk of metabolic syndrome (MetS) and low fat-free mass (FFM) on an individual's disability-free survival (DFS). Disability is defined as a composite of dementia, physical disability, and mortality. Using data from the Korean Genome and Epidemiology Study, we divided 3721 participants aged 40-69 years based on their MetS status and FFM index (FFMI) score. Kaplan-Meier survival analysis and Cox regression were used to analyze differences in DFS between the four groups. From 108 events, MetS group had significantly shorter DFS than the non-MetS group regardless of FFMI (p<0.0001). After adjusting other potential confounding variables, the MetS group had a higher risk of shortened DFS regardless of FFMI, and the MetS group with low FFMI had a 2.06-fold increased risk compared to the non-MetS group with high FFMI (p<0.001). Older age and lower income were also associated with higher risk of shorter DFS (p<0.001). The combination of MetS and low FFMI contribute to a cumulative risk of shortened DFS. Community nurses can perform MetS screening and body composition assessment to predict and control the risk of developing disability over time.

Prognostic Effect of the PNI and LSR in Patients with Esophageal Squamous Cell Carcinoma Patients Receiving Radiotherapy.

The prognostic nutritional index (PNI) has been used to assess the immunonutritional status of cancer patients and can predict the prognosis of various solid cancers, and the serum alanine transaminase (ALT)/aspartate transaminase (AST) ratio (LSR) is considered a good predictor of liver injury. A retrospective cohort analysis was conducted to investigate the relationship between the prognosis of esophageal squamous cell carcinoma (ESCC) patients and LSR or PNI, as well as to combine these two indicators (LSR-PNI) for further prognostic analysis in ESCC patients undergoing radiotherapy (RT). In this study, 134 patients with esophageal cancer were retrospectively analyzed. The Chi-square test was utilized to compare count data, and univariate and multivariate Cox proportional hazards models were employed to identify independent risk and prognostic factors. Additionally, the combination of LSR and PNI (LSR-PNI) was analyzed. This study included a cohort of 134 patients, comprising 105 males with a mean age of 70.7 years and 29 females with a mean age of 76.3 years. Pathological examination categorized 41 cases as stage I-II and 93 cases as stage III-IV. The predominant treatment modality administered was intensity-modulated radiotherapy (IMRT) for esophageal cancer. Of these patients, 96 received radiation doses ≤ 54Gy, while 38 were administered doses > 54Gy. Radiation-induced adverse effects were observed in 67 patients, with the remaining 67 showing no such effects. Kaplan-Meier survival analysis revealed that elevated levels of the lymphocyte-to-serum ratio (LSR) and prognostic nutritional index (PNI) were significantly correlated with improved progression-free survival (PFS) and overall survival (OS). The high-LSR group demonstrated longer PFS (14.4 vs. 9.3 months, p = 0.0469) and OS (19.9 vs. 13.7 months, p = 0.0315) compared to the low-LSR group, with respective 3-year survival rates of 18.4% vs. 12.7%. Similarly, patients in the high-PNI group exhibited superior PFS (13.9 vs. 8.9 months, p = 0.0071) and OS (19.0 vs. 13.5 months, p = 0.0002) compared to the low-PNI group, with 3-year survival rates of 19.6% vs. 11.3%. Stratification based on combined LSR and PNI levels categorized patients into low-, intermediate-, and high-risk groups. The low-risk group demonstrated significantly better PFS (17.8 vs. 10.1 vs. 8.2 months) and OS (24.1 vs. 14.3 vs. 12.9 months, p < 0.0001) compared to the intermediate- and high-risk groups, with 3-year survival rates of 24%, 14%, and 10.3%, respectively. Pretreatment LSR and PNI can serve as independent prognostic predictors for patients, with higher values of both being associated with improved progression-free survival and overall survival. Additionally, the combined LSR-PNI score effectively stratifies patients into distinct risk groups, offering a robust tool for predicting outcomes in clinical practice.

The impact of qualitative [18F]FDG PET/CT in predicting clinical outcomes of post-surgical differentiated thyroid cancer patients with elevated thyroglobulin and negative radioiodine whole-body scan

Background[18F]FDG PET/CT has been widely used as a diagnostic tool in detection and localization of recurrent non-avid radioiodine lesions in post-operative differentiated thyroid cancer (DTC) patients with elevated serum thyroglobulin but negative radioiodine whole-body scan (TENIS) syndrome. The aim of our study was to evaluate the role of [18F]FDG PET/CT in prediction on outcomes of these DTC patients.MethodsPost-operative DTC patients with TENIS syndrome were collected in the department of nuclear medicine, Hospital 108 from 2019 to 2023. Patients underwent [18F]FDG PET/CT with standard protocol following EANM guideline for tumor imaging version 2.0. The qualitative [18F]FDG PET/CT imaging characteristics were classified into three categories: (i) negative [18F]FDG PET/CT, (ii) minimal [18F]FDG PET/CT volume of lesions, (iii) extensive [18F]FDG PET/CT volume of lesions. Progression-free survival (PFS) and overall survival (OS) were the end point of the study. The prognosis of qualitative [18F]FDG PET/CT in predicting PFS and OS was illustrated by Kaplan–Meier survival analysis. The independent factors predicting PFS and OS were determined by univariate and multivariate analysis using logistic regression.ResultsThere were 164 consecutive patients, 51.2% female and 48.8% female. The most common histopathological type was papillary accounting for 91.5%. The median time of follow-up was 33.3 months, (range 6.57 – 82.5). There was 70 (36.6%) progressions and 12 (7.35%) deaths. Negative [18F]FDG PET/CT uptake patients had median PFS with median 57.1 months which was higher than that of minimal category (46.2 months), and extensive category (37.6 months) (p < 0,001). 1-year OS and 5-year OS in extensive PET/CT category was 97.8% and 86.2% respectively which were significantly lower than that of negative and minimal categories (p = 0.053). In multivariate analysis, age at the time of diagnosis, pulmonary, bone metastases and extensive [18F]FDG PET/CT volume of lesions were the independent factor predicting PFS. Bone metastasis was only the factor could predict OS in multivariate analysis.ConclusionsThe minimal and negative [18F]FDG PET/CT categories had better prognosis than extensive category in PFS and OS. Extensive [18F]FDG PET/CT category was an independent factor for predicting PFS. Bone metastasis was only the independent factor that could predict both PFS and OS.

Clinical significance of quantitative assessment of right ventricular amyloid burden with [99mTc]Tc-DPD SPECT/CT in transthyretin cardiac amyloidosis.

To evaluate right ventricular (RV) uptake measured by quantitative [99mTc]Tc-DPD SPECT/CT to investigate its role in predicting and evaluating prognosis and therapeutic outcomes in patients with transthyretin amyloid cardiomyopathy (ATTR-CA). Patients with ATTR-CA were consecutively enrolled for quantitative [99mTc]Tc-DPD SPECT/CT. Ventricular amyloid burden was quantified by SUVmax and TBR. Differences in RV uptake (focal or diffuse) and associations with clinical characteristics and CMR data were evaluated. The primary endpoint was major adverse cardiac events (MACEs), including all-cause deaths, heart failure hospitalizations, complete atrioventricular block, sustained ventricular tachycardia, and atrial fibrillation/flutter. Prognostic associations were evaluated using Cox regression and Kaplan-Meier survival analysis. A secondary endpoint involved a longitudinal SPECT/CT analysis during Tafamidis therapy. The study included 76 patients, all showing both RV and LV uptake on SPECT imaging. Compared with patients with focal RV uptake, patients with diffuse RV uptake had higher serum troponin T levels (P < 0.05), septal thickness (P < 0.01), and external cardiac circulation volume (ECV) (P < 0.05). RV uptake was correlated with septal thickness, ECV, LV uptake, NT-proBNP and troponin-T (all P < 0.05). Among 53 patients, high LV and RV uptake significantly predicted MACEs (P < 0.001), with a median follow-up time of 16 months. A subgroup of 20 patients showed significant reductions in LV and RV uptake after Tafamidis treatment (P < 0.001). Increasing RV amyloid burden quantified by SPECT/CT is associated with advanced disease stage and predicts MACEs, serving as valuable markers for prognosis and treatment monitoring in ATTR-CA.

Induction chemotherapy for locally advanced nasopharyngeal carcinoma: Efficacy and safety of the TPC regimen compared to GP and TPF

Background and objectivesGemcitabine plus cisplatin (GP) and docetaxel plus cisplatin plus fluorouracil (TPF) are induction chemotherapy (IC) regimens for locally advanced nasopharyngeal carcinoma (LA-NPC). The oral convenience of capecitabine presents its potential as a fluorouracil substitute in the TPF regimen, which has yet to be thoroughly investigated. This study aims to compare the efficacy and safety of the docetaxel, cisplatin, and capecitabine (TPC) with GP and TPF in LA-NPC. MethodsA retrospective analysis was conducted on newly diagnosed stage III-IVa nasopharyngeal carcinoma patients who received GP, TPC, or TPF induction chemotherapy followed by concurrent chemoradiotherapy (CCRT) between February 2019 and December 2021. A comparison of the prognostic outcomes and associated adverse reactions among patients receiving different IC regimens. Multivariate Cox regression was applied to analyze independent prognostic factors, and subgroup survival analyses were conducted based on these factors. ResultsA total of 291 LA-NPC patients were included, with 70 receiving TPC, 119 receiving GP, and 102 receiving TPF. Kaplan-Meier survival analysis indicated no significant differences in OS, PFS, LRFS, and DMFS among the 3 groups. Multivariate Cox regression identified T classification and clinical stage as independent prognostic factors. Subgroup analyses revealed no significant differences in OS and PFS between the 3 groups across T1-2 and T3-4 classifications or III and IVa stages.The TPC group exhibited lower incidence rates of treatment-related acute toxicity reactions, including grade 3–4 toxicities. ConclusionThe TPC induction chemotherapy regimen demonstrates comparable efficacy to GP and TPF, while maintaining a favorable safety profile.

Overcoming GABA-induced Treg suppression of immunity by ABAT to augment CD8+T cell anti-tumor immune response in liver cancer

Background: ABAT, a key enzyme in GABA catabolism, modulates anti-tumor immune activity across various cancers. However, the molecular mechanisms by which the ABAT/GABA axis exerts immune regulation in the liver cancer microenvironment remain unclear. Methods: ABAT expression in liver cancer tissues was scrutinized via the TCGA-LIHC database, and the 5-year survival rates of liver cancer patients were appraised through Kaplan-Meier survival analyses. The mRNA levels of ABAT in liver cancer cell lines were quantified by qRT-PCR. 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT), colony formation, and Transwell assays were employed to gauge the influence of ABAT overexpression on liver cancer cell growth, proliferation, migration, and invasion, respectively. Western blot evaluated EMT-related protein expression. ELISA quantified GABA, IL-10, TGF-β1, Granzyme B, and IFN-γ in the culture medium. Flow cytometry was used to measure the frequency of CD25+FOXP3+ cells and the expression of CD25, CD69, and PD-1 on CD8+T cells in co-culture. Carboxifluorescein diacetate succinimidyl ester (CFSE) dilution assays were performed to assess the proliferative activity of CD8+T cells. Results: ABAT was found to be underexpressed in liver cancer tissues and cells, and such underexpression is indicative of a poorer prognosis for patients, while its overexpression was shown to curb the malignancy of liver cancer cells. Upon overexpression of ABAT, there is a decrease in GABA levels in the cell supernatant, coupled with an increase in IL-10 and TGF-β1 cell number, and an upsurge in the CD25+FOXP3+ cell ratios, all of which were restored by the addition of exogenous GABA. Furthermore, the depletion of ABAT led to a reduction in the proliferation and tumor-killing ability of CD8+T cells, effects that were reversed by the application of GABAA receptor inhibitors. Conclusion: ABAT functions to inhibit Treg differentiation in liver cancer through downregulation of GABA, thus promoting the antitumor activity of CD8+T cells.

Contribution of HPV Status for Neutrophil Extracellular Traps Release in Oropharyngeal Cancer.

Oropharyngeal squamous cell carcinoma (OP-SCC) represents a public health problem and human papillomavirus (HPV) is one of the risk factors. Neutrophil extracellular traps (NET) are meshes of DNA strands and granule proteins. NET has been identified in diverse cancers, whether associated with viruses or not. However, there is no information on NET in OP-SCC. We aimed to evaluate the NET release by neutrophils in the OP-SCC microenvironment, stratified by HPV status. This cross-sectional study analyzed OP-SCC biopsy specimens diagnosed from 1997 to 2021. HPV status was determined by p16 immunohistochemistry and "in situ" hybridization. Neutrophils were detected by CD66b immunohistochemistry. Immunofluorescence was used to identify NET by co-localization of myeloperoxidase (MPO) and citrullinated histone H3 (H3Cit). Bivariate statistics, Kaplan-Meier survival analysis, and the log-rank test were performed. HPV-positive and HPV-negative OP-SCC had similar CD66b + neutrophil infiltration (p > 0.05), but the release of NET was significantly increased in HPV-positive compared to HPV-negative OP-SCC samples (p < 0.05). Overall survival was not impacted by NET indexes (p > 0.05). The presence of HPV may stimulate NET release in the OP-SCC microenvironment.

Stress hyperglycemia ratio association with all-cause mortality in critically ill patients with coronary heart disease: an analysis of the MIMIC-IV database

Background The stress hyperglycemia ratio (SHR) indicates relative hyperglycemia levels. Research on the impact of SHR on mortality in coronary heart disease (CHD) patients in intensive care is limited. This study explores the predictive accuracy of SHR for the prognosis of CHD patients in the ICU. Methods This study included 2,059 CHD patients from the American Medical Information Mart for Intensive Care (MIMIC-IV) database. SHR was determined using the formula: SHR = (admission glucose) (mmol/L) / (1.59 * HbA1c [%] – 2.59). Subjects were stratified into quartiles based on SHR levels to examine the correlation between SHR and in-hospital mortality. The restricted cubic splines and Cox proportional hazards models were employed to assess this association, while Kaplan-Meier survival analysis was executed to ascertain the mortality rates across the SHR quartiles. Results Among the 2059 participants (1358 men), the rates of in-hospital and ICU mortality were 8.5% and 5.25%, respectively. Analysis showed SHR as a significant predictor of increased risk for both in-hospital (HR,1.16, 95% CI: 1.02–1.32, P = 0.022) and ICU mortality (HR, 1.16, 95% CI: 1.01–1.35, P = 0.040) after adjustments. A J-shaped relationship was noted between SHR and mortality risks (p for non-linearity = 0.002, respectively). Kaplan-Meier analysis confirmed substantial differences in in-hospital and ICU mortality across SHR quartiles. Conclusions SHR significantly predicts in-hospital and ICU mortality in critically ill CHD patients, indicating that higher SHR levels correlate with longer ICU stays and increased mortality. This underscores the potential of SHR as a prognostic marker for ICU CHD patients.

Pain Relief Survivorship: A Comparison of Exactech Equinoxe Anatomic and Reverse Total Shoulder Arthroplasty for Primary Osteoarthritis

BackgroundPain-relief plays a major deterministic role when assessing postoperative patient satisfaction; however, whether anatomic total shoulder arthroplasty (aTSA) or reverse total shoulder arthroplasty (rTSA) provides the most durable pain-relief has not been studied. The purpose of this study was to evaluate the durability of pain-relief after aTSA compared to rTSA in patients undergoing surgery for rotator cuff-intact glenohumeral osteoarthritis (RCI-GHOA). MethodsA retrospective review of a multicenter shoulder arthroplasty database (Exactech Equinoxe) was performed. We included 1,848 aTSAs and 1,464 rTSAs performed for RCI-GHOA between 2007 and 2023. Pain after surgery was assessed postoperatively at 3-months, 6-months, and yearly thereafter. Average postoperative pain on a daily basis and pain at worst were compared between aTSA and rTSA up to 8-years postoperatively. Kaplan-Meier survivorship analysis for pain-relief maintenance was performed to compare the maintenance of clinically-relevant pain-relief defined as pain scores that achieved the minimal clinically important difference (MCID), substantial clinical benefit (SCB), and patient acceptable symptomatic state (PASS). Maintenance of favorable patient satisfaction over time was also evaluated. Multivariable cox regression was performed to determine whether the type of prosthesis (aTSA vs. rTSA) was independently associated with pain recurrence. ResultsMaintenance of achievement of the MCID and SCB for both daily pain and pain at worst as well as favorable patient satisfaction was similar between aTSAs and rTSAs. However, aTSA had longer maintenance of average daily pain below the PASS compared to rTSA (P=.024). This was confirmed on multivariable cox regression analysis which found that rTSAs had a 34% greater likelihood of recurrence of postoperative average daily pain exceeding the PASS (VAS rating 1/10) compared to aTSAs. ConclusionPatients that undergo either aTSA or rTSA for RCI-GHOA and achieve initial pain-relief postoperatively can expect to maintain their clinically-relevant pain improvement at similar rates up to 8-years postoperatively. However, recurrence of low levels of daily pain was significantly higher after rTSA.

Prognostic Influence of Lung Compliance in Patients with Cardiogenic Shock and Invasive Mechanical Ventilation.

There is limited data regarding the influence of lung compliance on the outcome of patients with cardiogenic shock (CS). Thus, a registry study was conducted to assess the prognostic influence of lung compliance in invasively ventilated patients with CS. Hospital records for consecutive invasively ventilated CS-patients from June 2019 to May 2021 were collected into a prospective registry. Our study evaluated the prognostic influence of lung compliance on 30-day all-cause mortality. Statistical analyses comprised t-tests, analysis of variance (ANOVA), Kruskal-Wallis-tests, Spearman's correlation, Kaplan-Meier survival analyses, and Cox regression. A total of 141 patients with CS requiring invasive mechanical ventilation were included. Stratification by quartiles revealed that patients with the lowest lung compliance (≤23.8 mL/cmH2O) experienced the highest mortality rates (77.1% vs. 66.7% vs. 48.6% vs. 51.4%; log-rank p = 0.018) both overall and among the subgroup of CS-patients with cardiac arrest (80% vs. 74% vs. 53% vs. 59%; log-rank p = 0.037). After stratifying by the median, patients with lung compliance <30.4 mL/cmH2O demonstrated a significantly higher 30-day all-cause mortality compared to those above this threshold (71.8% vs. 50.0%; log-rank p = 0.007) for both the overall cohort and the cardiac arrest subgroup (77.2% vs. 55.9%; log-rank p = 0.008). Multivariable adjustment confirmed that lung compliance <30.4 mL/cmH2O was significantly associated with increased 30-day all-cause mortality in the entire cohort (hazard ratio [HR] = 1.698; 95% CI 1.085-2.659; p = 0.021). Notably, this association was not significant in CS-patients with cardiac arrest (HR = 1.523; 95% CI 0.952-2.438; p = 0.080). Additionally, those with lung compliance below the median experienced fewer ventilator-free days (p = 0.003). In invasively ventilated CS-patients, low lung compliance was associated with higher all-cause mortality and fewer ventilator-free days at 30 days. NCT05575856, https://clinicaltrials.gov/study/NCT05575856.

Correlation of the triglyceride-glucose index and heart rate with 28-day all-cause mortality in severely ill patients: analysis of the MIMIC-IV database

BackgroundResearch has identified a link between the triglyceride-glucose index (TyG-i) and the risk of mortality in severely ill patients. However, it remains uncertain if the TyG-i affects mortality by influencing heart rate (HR).MethodsThis study enrolled 3,509 severely ill participants from the Medical Information Mart for Intensive Care (MIMIC-IV) database who had triglyceride, glucose, and HR data upon entering the ICU. Cox regression models were applied to estimate the effect of the TyG-i and HR on 28-day all-cause mortality (ACM) and 28-day in-hospital mortality (IHM). Additionally, Kaplan-Meier (K-M) survival analysis was employed to explore outcome variations among different patient groups. The association of the TyG-i with HR, Sequential Organ Failure Assessment (SOFA) score, and Simplified Acute Physiology Score (SAPS) II was explored through linear regression analysis. Subgroup analysis explored potential interactions among patient characteristics, while sensitivity analysis gauged the robustness of the findings. Additionally, mediation analysis was conducted to assess whether elevated HR acts as an intermediary factor linking the TyG-i to both 28-day ACM and 28-day IHM.ResultsDuring the 28-day follow-up, 586 cases (16.7%) died from all causes, and 439 cases (12.5%) died during hospitalisation. Cox results showed that individuals with a heightened TyG-i and elevated HR had the highest 28-day ACM (Hazard Ratio 1.70, P-value below 0.001) and 28-day IHM (Hazard Ratio 1.72, P-value below 0.001) compared to those with a reduced TyG-i and HR. The K-M curves showed that individuals with low TyG-i and low HR had the lowest incidence of 28-day ACM and 28-day IHM. The linear analysis results evidenced that the TyG-i was independently connected to HR (beta = 3.05, P-value below 0.001), and the TyG-i was also independently associated with SOFA score (beta = 0.39, P-value below 0.001) and SAPS II (beta = 1.79, P-value below 0.001). Subgroup analysis revealed a significant association in participants without hypertension, the interaction of an elevated TyG-i and HR strongly correlated with a higher 28-day death risk (interaction P-value below 0.05). Furthermore, HR mediated 29.5% of the connection between the TyG-i and 28-day ACM (P-value = 0.002), as well as 20.4% of the connection between the TyG-i and 28-day IHM (P-value = 0.002).ConclusionFor severely ill patients, the TyG-i is distinctly correlated with HR, and elevated levels of both are strongly connected to greater 28-day ACM and 28-day IHM risks, especially in patients without hypertension. Furthermore, elevated HR mediates the connection between the TyG-i and 28-day mortality.

Efficacy and safety of sacubitril/valsartan on postoperative atrial fibrillation in adult patients undergoing cardiac surgery: a real-world observational study.

The mechanism underlying new-onset postoperative atrial fibrillation (POAF) in adult cardiac surgery is not well understood. However, efficient pharmacological methods to prevent and treat arrhythmic complications are still lacking. In the present study, we explored the efficacy and safety of sacubitril/valsartan (sac/val) in the control of POAF in adult cardiac surgery patients. Between January 2021 and December 2021, 667 eligible adult patients who underwent cardiac surgery at the Affiliated Hospital of Qingdao University were enrolled. The participants were divided into two groups according to whether sac/val was used: the sac/val group (N = 101) and the control group (N = 566). The main observational endpoints were the incidence of POAF, left ventricular ejection fraction (LVEF) recovery, in-hospital mortality, and short-term mortality. Patients in the sac/val group had a lower incidence of POAF than those in the control group (26/101 vs. 204/566, P = 0.045). Patients in the sac/val group also showed a higher communicative risk for POAF incidence using the Kaplan-Meier survival analysis. In addition, patients in the sac/val group showed better LVEF recovery, with dynamic changes in LVEF superior to that of the control group. The change in LVEF in the sac/val group was 1.78 ± 5.41, compared with -1.19 ± 10.92 in the control group (P = 0.008). This is the first observational study to evaluate the efficacy and safety of sac/val in the prevention and treatment of POAF after cardiac surgery. The results demonstrated that compared with patients who did not receive sac/val treatment, those who received Sac/val treatment showed better POAF control and LVEF recovery. These results should be cautiously interpreted and further confirmed using larger sample sizes and prospective randomized controlled trials.

Ion channel modulator DPI-201-106 significantly enhances anti-tumour activity of DNA damage response inhibitors in glioblastoma

Abstract Background Glioblastoma, a lethal high-grade glioma, has not seen improvements in clinical outcomes in nearly 30 years. Ion channels are increasingly associated with tumourigenesis, and there are hundreds of brain-penetrant drugs that inhibit ion channels, representing an untapped therapeutic resource. The aim of this exploratory drug study was to screen an ion channel drug library against patient-derived glioblastoma cells to identify new treatments for brain cancer. Methods 72 ion channel inhibitors were screened in patient-derived glioblastoma cells, and cell viability was determined using the ViaLight Assay. Cell cycle and apoptosis analysis was determined with flow cytometry using PI and Annexin V staining, respectively. Protein and phosphoprotein expression was determined using mass spectrometry and analysed by gene set enrichment analysis. Kaplan-Meier survival analyses were performed using intracranial xenograft models of GBM6 and WK1 cells. Results The voltage-gated sodium channel modulator, DPI-201-106, was revealed to reduce glioblastoma cell viability in vitro by inducing cell cycle arrest and apoptosis. Phosphoproteomics indicated that DPI-201-106 may impact DNA damage response pathways. Combination treatment of DPI-201-106 with the CHK1 inhibitor prexasertib or the PARP inhibitor niraparib demonstrated synergistic effects in multiple patient-derived glioblastoma cells both in vitro and in intracranial xenograft mouse models, extending survival of glioblastoma-bearing mice. Conclusion DPI-201-106 enhances the efficacy of DNA damage response inhibitors to reduce glioblastoma growth. As these drugs have already been clinically tested in humans, repurposing DPI-201-106 in novel combinatorial approaches will allow for rapid translation into the clinic.

Preliminary Analysis of Incidence, Risk Factors, and Management of Medication-Related Osteonecrosis of the Jaw in Cancer Patients

BackgroundMedication-related osteonecrosis of the jaw (MRONJ) is a severe complication associated with antiresorptive and antiangiogenic therapies commonly used to manage bone metastasis and improve bone density in cancer patients. This study aimed to investigate MRONJ's incidence, risk factors, and outcomes of MRONJ in patients receiving these therapies. MethodsA retrospective cohort study was conducted involving 98 patients who had received antiresorptive or antiangiogenic medications for at least one year. Data were collected from the electronic health records, focusing on demographics, medication details, comorbidities, dental history, and MRONJ status. Logistic regression analysis was used to identify predictors of MRONJ, and Kaplan-Meier survival analysis was used to assess treatment outcomes, comparing surgical and conservative management approaches. ResultsThe incidence of MRONJ was 21.4% among the study cohort. Logistic regression identified prolonged medication duration (odds ratio [OR] =2.5; p=0.01), comorbidities (OR=3.2; p=0.003), and prior dental procedures (OR=2.1; p=0.02) as significant predictors of MRONJ. Kaplan-Meier analysis showed that surgical intervention resulted in longer survival (median 24.5 Â months) than conservative management (median 12.8 months; p<0.01). Despite the high rates of healing (71.4%) and pain management success (85.7%), a recurrence rate of 23.8% indicated MRONJ’s chronic nature of MRONJ. ConclusionThis study underscores the importance of early identification and interdisciplinary management of MRONJ risk factors, particularly in patients with prolonged antiresorptive or antiangiogenic therapy. Surgical intervention appears beneficial; however, high recurrence rates emphasize the need for vigilant monitoring and patient-specific treatment strategies.

Machine Learning-Based Prognostic Gene Signature for Early Triple Negative Breast Cancer.

This study aimed to develop a machine learning-based approach to identify prognostic gene signatures for early-stage Triple Negative Breast Cancer (TNBC) using next-generation sequencing data from Asian populations. We utilized next-generation sequencing data to analyze gene expression profiles and identify potential biomarkers. Our methodology involved integrating various machine learning techniques, including feature selection and model optimization. We employed logistic regression, Kaplan-Meier survival analysis, and receiver operating characteristic (ROC) curves to validate the identified gene signatures. We identified a gene signature significantly associated with relapse in TNBC patients. The predictive model demonstrated robustness and accuracy, with an area under the ROC curve (AUROC) of 0.9087, sensitivity of 0.8750, and specificity of 0.9231. The Kaplan-Meier survival analysis revealed a strong association between the gene signature and patient relapse, further validated by logistic regression analysis. This study presents a novel machine learning-based prognostic tool for TNBC, offering significant implications for early detection and personalized treatment. The identified gene signature provides a promising approach for improving the management of TNBC, contributing to the advancement of precision oncology.

Decreasing Endomyocardial Biopsy Frequency in Pediatric Heart Transplantation Using A Rejection Risk Prediction Score-A Single Center Study.

Rejection remains an important cause of morbidity and mortality after pediatric heart transplantation (HT). Endomyocardial biopsy (EMB) is the gold standard for rejection diagnosis, but it comes with procedural risk. The frequency of EMB varies significantly across centers. Since April 2018, our center's surveillance EMB schedule is based on a rejection risk prediction score employing age, pre-HT diagnosis, and panel reactive antibodies (PRA). We aimed to evaluate outcomes in the 1st year post-HT before and after risk score implementation. Patients who underwent HT at our center at ≤ 18 years of age from January 2015 to December 2020 were reviewed. The primary endpoint was rejection-free survival at 1 year-post- HT. Clinical characteristics were compared for patients transplanted in Era 1 (January 2015-April 2018) and Era 2 (April 2018-December 2020). Cumulative 1-year survival free from rejection and from rejection with hemodynamic compromise (RHC) was compared between eras using Kaplan-Meier survival analysis. 115 patients underwent HT during our study period (52 in Era 1 and 63 in Era 2). There was an increase in VAD utilization between eras (19% in Era 1 vs. 40% in Era 2, p = 0.025), but otherwise no significant difference in demographic or clinical variables between the two eras. No statistically significant difference in freedom from rejection or freedom from RHC was identified between the two eras. There was a 60% reduction in the median number of EMB per patient in the first year post-HT after employing the score (5 in Era 1 vs. 2 in Era 2, p < 0.001). After employing a rejection risk prediction score, our center decreased the frequency of EMB without worsening early post-HT outcomes, thus establishing the clinical applicability of this tool.

Survival Analysis of Prefabricated Zirconia Crowns with and Without Pulpotomy in Primary Teeth: A Retrospective Cohort Study.

Prefabricated Zirconia Crowns (PZCs) are increasingly preferred for restoring primary teeth due to their esthetic appeal and retention. However, their rigid, unmodifiable design requires precise tooth preparation, often leading to aggressive reduction and potential pulp exposure. Pulpotomy, a standard treatment for reversible pulpitis and mechanical pulp exposure, is sometimes employed before PZCs. While pulpotomy is not routinely performed, its use raises important considerations about the interplay between restorative procedures and pulp therapy in pediatric dentistry, particularly regarding the long-term restoration outcomes of PZCs. This study aimed to investigate the impact of pulpotomy on the success rate of PZCs. We examined 81 anterior upper primary teeth treated with PZCs in children aged 2-5 years over a two-year period. Cases were divided into groups with and without pulpotomy. Follow-ups occurred at 6-month intervals, assessing clinical and radiographic outcomes. Analyses were performed using SPSS 25.0 software. The statistical significance was p < 0.05. A total of 81 anterior primary teeth were included. Chi-square analysis showed no association between pulp therapy and PZC success (χ2 = 0.051, p = 0.822). The Kaplan-Meier survival analysis revealed comparable survival curves and the log-rank test showed no statistically significant difference in survival time between pulpotomy-treated and untreated groups (χ2 = 0.051, p = 0.821). Pulpotomy did not significantly affect the success rate of PZCs within 2 years.

Abstract B028: The Role of cDC1 Gene Signatures in gastric cancer prognosis and immune microenvironment modulation

Abstract Background and Aim: Gastric cancer (GC) continues to be a major global health burden, with a growing body of evidence highlighting the critical role of conventional type 1 dendritic cells (cDC1s) within the tumor microenvironment. This study aims to elucidate the prognostic significance of cDC1-associated genes—CD141, XCR1, CLEC9A, CADM1, and BTLA—in gastric cancer, as well as to explore the biological mechanisms that underpin their effects on patient outcomes. Materials and Methods: We conducted a comprehensive analysis of RNA- seq data from The Cancer Genome Atlas (TCGA-STAD) and Gene Expression Omnibus (GEO) datasets, focusing on the expression profiles of five cDC1-related genes. Patients were stratified into high and low expression groups based on a defined cDC1 gene signature. To assess the impact of these signatures, we utilized gene set variation analysis (GSVA) to examine relevant oncogenic pathways and performed Kaplan-Meier survival analysis along with Cox proportional hazards modeling to evaluate their prognostic value. Results: Our findings demonstrate that patients exhibiting a high cDC1-related gene signature had significantly worse overall and disease-free survival within the TCGA-STAD cohort. Further analysis revealed marked differences in CD8+ T cell infiltration and cytotoxic activity between the high and low cDC1 signature groups. Additionally, the high cDC1 signature group was strongly associated with upregulated expression of immune checkpoint proteins and the activation of oncogenic pathways, indicating a highly immunosuppressive tumor microenvironment. Conclusions: This study suggests that the cDC1-related gene signature may serve as a potent prognostic biomarker in gastric cancer, offering new insights into the complex interactions between the tumor and immune microenvironment. These results could pave the way for innovative therapeutic strategies that target the immune landscape in gastric cancer, potentially improving patient outcomes. Citation Format: Song-hee han. The Role of cDC1 Gene Signatures in gastric cancer prognosis and immune microenvironment modulation [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: Tumor-body Interactions: The Roles of Micro- and Macroenvironment in Cancer; 2024 Nov 17-20; Boston, MA. Philadelphia (PA): AACR; Cancer Res 2024;84(22_Suppl):Abstract nr B028.