Independent Predictor Of Outcome Research Articles

Derivation and Validation of a Scoring System for Predicting Poor Outcome After Posterior Circulation Ischemic Stroke in China.

Guidelines for posterior circulation ischemic stroke (PCIS) treatment are lacking and outcome prediction is crucial for patients and clinicians. We aimed to develop and validate a prognostic score to predict the poor outcome for patients with PCIS. The score was developed from a prospective derivation cohort named the Third China National Stroke Registry (August 2015-March 2018) and validated in a spatiotemporal independent validation cohort (December 2017-March 2023) in China. Patients with PCIS with acute infarctions defined as hyperintense lesions on diffusion-weighted imaging were included in this study. The poor outcome was measured as modified Rankin scale (mRS) score 3-6 at 3 months after PCIS. Multivariable logistic regression analysis was used to identify predictors for poor outcome. The prognostic score, namely PCIS Outcome Score (PCISOS), was developed by assigning points to variables based on their relative β-coefficients in the logistic model. The PCISOS was derived from 3,294 patients (median age 62 [interquartile range (IQR) 55-70] years; 2,250 [68.3%] men) and validated in 501 patients (median age 61 [IQR 53-68] years; 404 [80.6%] men). Among them, 384 (11.7%) and 64 (12.8%) had poor outcome 3 months after stroke in respective cohorts. Age, mRS before admission, NIH Stroke Scale on admission, ischemic stroke history, infarction distribution, basilar artery, and posterior cerebral artery stenosis or occlusion were identified as independent predictors for poor outcome and included in PCISOS. This easy-to-use integer scoring system identified a marked risk gradient between 4 risk groups. PCISOS performed better than previous scores, with an excellent discrimination (C statistic) of 0.80 (95% CI 0.77-0.83) in the derivation cohort and 0.81 (95% CI 0.77-0.84) in the validation cohort. Calibration test showed high agreement between the predicted and observed outcomes in both cohorts. PCISOS can be applied for patients with PCIS with acute infarctions to predict functional outcome at 3 months post-PCIS. This simple tool helps clinicians to identify patients with PCIS with higher risk of poor outcome and provides reliable outcome expectations for patients. This information might be used for personalized rehabilitation plan and patient selection for future clinical trials to reduce disability and mortality.

Association between defibrillation-to-adrenaline interval and short-term outcomes in patients with out-of-hospital cardiac arrest and an initial shockable rhythm

AimThe optimal timing of adrenaline administration after defibrillation in patients with out-of-hospital cardiac arrest (OHCA) and an initial shockable rhythm is unknown. We investigated the association between the defibrillation-to-adrenaline interval and clinical outcomes. MethodsBetween 2011 and 2020, we enrolled 1,259,960 patients with OHCA into a nationwide prospective population-based registry in Japan. After applying exclusion criteria, 20,905 patients with an initial shockable rhythm documented at emergency medical services (EMS) arrival who received adrenaline after defibrillation were eligible for this study. Multivariable logistic regression analysis was used to predict favourable short-term outcomes: prehospital return of spontaneous circulation (ROSC), 30-day survival, or a favourable neurological outcome (Cerebral Performance Category 1 or 2) at 30 days. Patients were categorised into 2-minute defibrillation-to-adrenaline intervals up to 18 min, or more than 18 min. ResultsAt 30 days, 1,618 patients (8%) had a favourable neurological outcome. The defibrillation-to-adrenaline interval in these patients was significantly shorter than in patients with an unfavourable neurological outcome [8 (5–12) vs 11 (7–16) minutes; P < 0.001]. The proportion of patients with prehospital ROSC, 30-day survival, or a favourable neurological outcome at 30 days decreased as the defibrillation-to-adrenaline interval increased (P < 0.001 for trend). Multivariable analysis revealed that a defibrillation-to-adrenaline interval of > 6 min was an independent predictor of worse prehospital ROSC, 30-day survival, or neurological outcome at 30 days when compared with an interval of 4–6 min. ConclusionA longer defibrillation-to-adrenaline interval was significantly associated with worse short-term outcomes in patients with OHCA and an initial shockable rhythm.

Outcome of emergency neurosurgery in patients with refractory and super-refractory status epilepticus: a systematic review and individual participant data meta-analysis

BackgroundRefractory (RSE) and super-refractory status epilepticus (SRSE) are serious neurological conditions requiring aggressive management. Beyond anesthetic agents, there is a lack of evidence guiding management in these patients. This systematic review and individual participant data meta-analysis (IPDMA) seeks to evaluate and compare the currently available surgical techniques for the acute treatment of RSE and SRSE.MethodsA systematic review was performed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses for Individual Participant Data (PRISMA-IPD). Only patients who underwent surgery while in RSE and SRSE were included. Descriptive statistics were used to compare various subgroups. Multivariable logistic regression models were constructed to identify predictors of status epilepticus (SE) cessation, long-term overall seizure freedom, and favorable functional outcome (i.e., modified Rankin score of 0–2) at last follow-up.ResultsA total of 87 studies including 161 participants were included. Resective surgery tended to achieve better SE cessation rate (93.9%) compared to non-resective techniques (83.9%), but this did not reach significance (p = 0.071). Resective techniques were also more likely to achieve seizure freedom (69.1% vs. 34.4%, p = &amp;lt;0.0001). Older age at SE (OR = 1.384[1.046–1.832], p = 0.023) was associated with increased likelihood of SE cessation, while longer duration of SE (OR = 0.603[0.362–1.003], p = 0.051) and new-onset seizures (OR = 0.244[0.069–0.860], p = 0.028) were associated with lower likelihood of SE cessation, but this did not reach significance for SE duration. Only shorter duration of SE prior to surgery (OR = 1.675[1.168–2.404], p = 0.0060) and immediate termination of SE (OR = 3.736 [1.323–10.548], p = 0.014) were independently associated with long-term seizure status. Rates of favorable functional outcomes (mRS of 0–2) were comparable between resective (44.4%) and non-resective (44.1%) techniques, and no independent predictors of outcome were identified.ConclusionOur findings suggest that emergency neurosurgery may be a safe and effective alternative in patients with RSE/SRSE and may be considered earlier during the disease course. However, the current literature is limited exclusively to small case series and case reports with high risk of publication bias. Larger clinical trials assessing long-term seizure and functional outcomes are warranted to establish robust management guidelines.

AKR1B10 expression characteristics in hepatocellular carcinoma and its correlation with clinicopathological features and immune microenvironment

Hepatocellular carcinoma (HCC) represents a major global health threat with diverse and complex pathogenesis. Aldo–keto reductase family 1 member B10 (AKR1B10), a tumor-associated enzyme, exhibits abnormal expression in various cancers. However, a comprehensive understanding of AKR1B10's role in HCC is lacking. This study aims to explore the expression characteristics of AKR1B10 in HCC and its correlation with clinicopathological features, survival prognosis, and tumor immune microenvironment, further investigating its role and potential regulatory mechanisms in HCC. This study conducted comprehensive analyses using various bioinformatics tools and databases. Initially, differentially expressed genes related to HCC were identified from the GEO database, and the expression of AKR1B10 in HCC and other cancers was compared using TIMER and GEPIA databases, with validation of its specificity in HCC tissue samples using the HPA database. Furthermore, the relationship of AKR1B10 expression with clinicopathological features (age, gender, tumor size, staging, etc.) of HCC patients was analyzed using the TCGA database's LIHC dataset. The impact of AKR1B10 expression levels on patient prognosis was evaluated using Kaplan–Meier survival analysis and the Cox proportional hazards model. Additionally, the correlation of AKR1B10 expression with tumor biology-related signaling pathways and tumor immune microenvironment was studied using databases like GSEA, Targetscan, and others, identifying microRNAs (miRNAs) and long non-coding RNAs (lncRNAs) that regulate AKR1B10 expression to explore potential regulatory mechanisms. Elevated AKR1B10 expression was significantly associated with gender, primary tumor size, and fibrosis stage in HCC tissues. High AKR1B10 expression indicated poor prognosis and served as an independent predictor for patient outcomes. Detailed mechanism analysis revealed a positive correlation between high AKR1B10 expression, immune cell infiltration, and pro-inflammatory cytokines, suggesting a potential DANCR-miR-216a-5p-AKR1B10 axis regulating the tumor microenvironment and impacting HCC development and prognosis. The heightened expression of AKR1B10 in HCC is not only related to significant clinical-pathological traits but may also influence HCC progression and prognosis by activating key signaling pathways and altering the tumor immune microenvironment. These findings provide new insights into the role of AKR1B10 in HCC pathogenesis and highlight its potential as a biomarker and therapeutic target.

The impact of comorbidities on prolonged mechanical ventilation in patients with chronic obstructive pulmonary disease

BackgroundIn patients with chronic obstructive pulmonary disease (COPD) and acute respiratory failure, approximately 10% of them are considered to be at high risk for prolonged mechanical ventilation (PMV, > 21 days). PMV have been identified as independent predictors of unfavorable outcomes. Our previous study revealed that patients aged 70 years older and COPD severity were at a significantly higher risk for PMV. We aimed to analyze the impact of comorbidities and their associated risks in patients with COPD who require PMV.MethodsThe data used in this study was collected from Kaohsiung Medical University Hospital Research Database. The COPD subjects were the patients first diagnosed COPD (index date) between January 1, 2012 and December 31, 2020. The exclusion criteria were the patients with age less than 40 years, PMV before the index date or incomplete records. COPD and non-COPD patients, matched controls were used by applying the propensity score matching method.ResultsThere are 3,744 eligible patients with COPD in the study group. The study group had a rate of 1.6% (60 cases) patients with PMV. The adjusted HR of PMV was 2.21 (95% CI 1.44–3.40; P < 0.001) in the COPD patients than in non-COPD patients. Increased risks of PMV were found significantly for patients with diabetes mellitus (aHR 4.66; P < 0.001), hypertension (aHR 3.20; P = 0.004), dyslipidemia (aHR 3.02; P = 0.015), congestive heart failure (aHR 6.44; P < 0.001), coronary artery disease (aHR 3.11; P = 0.014), stroke (aHR 6.37; P < 0.001), chronic kidney disease (aHR 5.81 P < 0.001) and Dementia (aHR 5.78; P < 0.001).ConclusionsAge, gender, and comorbidities were identified as significantly higher risk factors for PMV occurrence in the COPD patients compared to the non-COPD patients. Beyond age, comorbidities also play a crucial role in PMV in COPD.

Investigating long-term outcomes and predictors of primary outcomes in patients treated for cardiac implantable electronic device infections

Abstract Background The estimated current infection rate after cardiac implantable electronic devices (CIED) implantation ranges between 1% and 2%, with variations in the literature from 0.13% to 12.6% (2). The rise in CIED implantation rates over the years has led to an escalation in the frequency of device-related infections. This trend is compounded by the elongation of patient comorbidities and life expectancy (3). Purpose The study aimed to investigate the primary outcome rates (including death, myocardial infarction (MI), cerebrovascular accidents (CVA), and reinfection) and identify predictors of primary outcomes in patients receiving treatment for CIED infection. Methods A retrospective analysis was conducted at a single-center. The study encompassed 2322 patients who sought treatment at the arrhythmia clinic of our Institute between March 2011 and July 2020 and underwent CIED implantation. After excluding 20 patients with active infections and 3 patients postoperative cardiac arrest, 36 patients were diagnosed with CIED infection (1.55% incidence). Diagnosis was based on the Novel 2019 International CIED Infection Criteria. Patients were categorized into groups based on the occurrence of all-cause death, MI, CVA, and reinfection during the follow-up period. Results The median follow-up period post admission with CIED infection was 42.5 (7-141) months. Table 1 presents patient characteristics, procedure details, and management-related parameters in the groups stratified by the primary endpoint. Notably, 58.3% of the patients had previously undergone a replacement procedure. Among patients with CIED infection, reinfection was observed in 20.0% of those who had a de novo procedure and 38.1% of those who underwent a secondary procedure (p: 0.25). Cox regression analysis revealed that pre-procedure C-reactive protein (CRP) levels and CHA2DS2-VASc score were independent predictors of the primary outcome (OR: 1.03 (1.00-1.06); P: 0.035, OR: 1.34(1.03-1.88); P: 0.030, respectively) (Table 2). Conclusion Long-term outcomes in patients with CIED infection appear to be correlated with pre-procedure CRP levels, indicating the severity of infection, and the CHA2DS2-VASc score, providing valuable insights into patient comorbidities. These factors seem to outweigh the impact of the specific procedure and antibiotic regimens administered. Management should not only focus on the history of CIED infection during follow-up but also prioritize the management of existing comorbidities to improve outcomes. Given the study's limitations such as the small sample size and retrospective nature, further investigations are warranted to confirm these findings.Table 1Table 2

Right ventricular systolic pressure is an independent risk factor of all-cause death and inappropriate therapies in patients with implanted CRT-D

Abstract Introduction Cardiac resynchronization therapy-defibrillators (CRT-D) are implanted mostly in patients with low left ventricular ejection fraction (LVEF) and wide QRS. In such subjects, there is often a concomitant right ventricular (RV) dysfunction, which has been associated with higher long-term mortality. However, data on the association between RV dysfunction and arrhythmic outcomes in patients with CRT-D are scarce. Purpose To define whether there is any association between right ventricular dysfunction and antiarrhythmic therapies or all-cause mortality in patients with HF and CRT-D. Methods The clinical and demographic data of patients enrolled in this study were obtained from the single-centre COMMIT-HF registry. The parameters regarding right ventricular function, such as right ventricle dimension (RVD), tricuspid annular systolic plane systolic excursion (TAPSE) and right ventricular systolic pressure (RVSP) were obtained from electronic patients’ records. The data on the long-term hard endpoints were obtained from the national healthcare provider, while the data on the risk of arrhythmic events, CRT-D shocks and antitachycardia pacing (ATP) were obtained from investigator-initiated and -adjudicated single-centre remote monitoring database updated annually. Multivariable stepwise logistic regression was used to determine independent predictors of the study outcomes, being all-cause death, and the occurrence of appropriate and inappropriate CRT-D therapies. Results During the period between July, 2009 and November, 2019, 335 patients were enrolled at the RM programme after implantation of CRT-D. Of them, during the median (Q1-Q3) follow-up period of 5.3 (2.8-6.6) years, (113 (33.7%) died, 111 (33.1%) received appropriate and 37 (11%) inappropriate therapies. In the multivariable analysis, the independent predictors of all-cause death were reduction in LVEF and increase in RVSP. Lower age and increased LVEDD were independent predictors of appropriate therapies, while lower age and increased RVSP were independent predictors of inappropriate therapies. No association between TAPSE and RVD and outcomes was found. Conclusions Among right ventricular dysfunction parameters, RVSP is an independent predictor of inappropriate therapies and all-cause death, but not of appropriate therapies in patients with HF and CRT-D.

Incidence and predictors of heart failure events following cardiac surgery in patients with atrial fibrillation - insights from the LAAOS-III trial

Abstract Background Atrial fibrillation (AF) is a common comorbidity in patients undergoing cardiac surgery and further increases the risk of incident heart failure (HF). However, only limited data exist on HF events following surgery in patients with AF. Methods The Left Atrial Appendage Occlusion Study (LAAOS) III was a randomized trial evaluating concomitant left atrial appendage occlusion in patients with AF undergoing cardiac surgery. In this secondary analysis, we aimed to identify independent predictors of the composite outcome of HF hospitalization or HF-related death following discharge, using a multivariable Cox model – incorporating sex, age (≥65 vs &amp;lt;65 years), systolic blood pressure (≤140 vs &amp;gt;140 mmHg), body mass index (BMI; &amp;lt;25 vs 25-29.9 vs ≥30 kg/m2), diabetes mellitus (DM), prior HF diagnosis, prior stroke, ischemic heart disease (IHD), heart valve surgery, AF history duration, rhythm on discharge electrocardiogram, and trial allocation. Supplementary analyses were undertaken to further assess the continuous variables using cubic spline regression. Results Of 4770 patients enrolled, in-hospital death occurred in 201 (4.2%) and complete discharge data were available for 4564 (95.7%). During a median follow up of 3.9 years, 533 (11.7%) of 4564 patients were hospitalized for HF. In total, 873 (19.1%) died after discharge, including 95 HF-related deaths. The composite outcome of HF hospitalization or HF-related death occurred at an annualized event rate of 3.31%/year [95% confidence interval: 3.04-3.60]. The independent risk factors included age (event rate of 3.64%/year vs 2.03%/year for ≥65 vs &amp;lt;65 years; hazard ratio (HR) 1.71 [1.32-2.21]), DM (4.71%/year vs 2.71%/year for with vs without DM; HR 1.59 [1.34-1.90]), prior HF diagnosis (4.27%/year vs 2.17%/year for with vs without HF; HR 2.00 [1.66-2.41]), IHD (3.63%/year vs 2.85%/year for with vs without IHD; HR 1.26 [1.03-1.54]), AF history duration (3.81%/year vs 2.89%/year for &amp;gt;2 vs &amp;lt;0.5 years; HR 1.23 [1.01-1.50]), and AF rhythm at discharge (3.87%/year vs 2.68%/year for AF vs non-AF rhythm; HR 1.31 [1.09-1.58]). The supplementary spline analyses further revealed a positive correlation between BMI and the risk of the composite outcome (p-value 0.042). Conclusions In patients with AF undergoing cardiac surgery, post-discharge HF hospitalization and HF-related death occurred at a rate of 3.31% per year. Our study identified several significant risk factors including advanced age, higher BMI, DM, prior HF diagnosis, IHD, AF history &amp;gt;2 years, and AF rhythm at discharge.The associations of HF with age and BMI

Constitutive type-1 interferons signaling activity in malignant gliomas.

Recent studies revealed a pro-tumor effect of constitutive Type-1 interferons (IFN-I) production and the downstream signaling activity in several malignancies. In contrast, heterogeneity and clinical significance of the signaling activity in gliomas remain unknown. Thus, we aimed to depict the heterogeneity and clinical significance of constitutive Type-1 interferon (IFN-I) production and the downstream signaling activity in gliomas. We utilized multiplex immunofluorescence (mIF) on a 364 gliomas tissue microarray from our cohort. Moreover, we conducted bioinformatic analyses on the Cancer Genome Atlas (TCGA) and the Chinese Glioma Genome Atlas (CGGA) databases to investigate the heterogeneity and clinical significance of constitutive IFN-I signaling activity in gliomas. We observed high heterogeneity of the constitutive IFN-I signaling activity among glioma subtypes. Signaling increased with the WHO malignancy grade while decreasing in the gliomas with IDH mutations. Additionally, high IFN-I activity served as an independent predictor of unfavorable outcomes, and global DNA hypermethylation in IDH-mutant gliomas was associated with decreased IFN-I signaling activity. Positive correlations were observed between the IFN-I activity and glioma-associated inflammation, encompassing both anti-tumor and pro-tumor immune responses. Furthermore, the IFN-I activity varied significantly among tumor and immune cells in the glioma microenvironment (GME). Notably, a distinct pattern of IFN-I signaling activity distribution in GME cells was observed among glioma subtypes, and the pattern was independently associated with patient overall survival. Constitutive IFN-I signaling activity varies significantly among glioma subtypes and represents a potential indicator for increased glioma inflammation and unfavorable clinical outcomes.

#3001 MtDNA copy number correlates to coronary artery calcium score and biological age in kidney failure patients

Abstract Background and Aims Chronic kidney disease (CKD) and kidney failure are connected to increased oxidative stress and vascular calcification, which are indicators for development of comorbidities and mortality outcome. Mitochondrial (mt)DNA copy number has been reported as independent predictor for frailty and mortality outcome of various cardiovascular diseases (CVD) and cancer. We aimed that mtDNA copy number in whole blood of kidney failure patients can be correlated to coronary artery media calcification score and coronary artery calcium (CAC) score and be used as an independent predictor for comorbidities and mortality outcome. Method Quantitative PCR (qPCR) with TaqMan® probes for three mtDNA genes (mtND1, mtND4 and mtCOX1) and two single locus genes on nuclear DNA (hemoglobin subunit beta and 18S), for normalization, is performed on DNA samples isolated from collected blood of 196 kidney transplant donors and 211 recipients at basal timepoint and 32 at 1-year-follow-up timepoint, included in the KaroKidney biobank. Resulting mtDNA copy number is investigated for correlation to CAC score, patient mortality outcome, biological age determined by skin autofluorescence and other clinical parameters. Results In our Swedish kidney transplant cohort we can see statistically significant difference in mtDNA copy number between kidney failure patients (recipients) and healthy controls (donors). No obvious difference between females and males was observed. mtDNA copy number correlates to biological age determined by skin autofluorescence, CAC score and Framingham CVD risk score. In the 32 1-year-follow-up samples we could see significant increase/recovery of mtDNA copy number for male patients compared to their baseline before receiving a transplant. Conclusion In this study we show that mtDNA copy number in kidney failure patients correlates to biological age and CAC score, affirming mtDNA copy number as an independent predictor of frailty in this Swedish cohort of CKD patients. Additionally, we can see that a kidney transplant can lead to a significant increase of mtDNA copy number in blood one year later, suggesting a general increase in health quality.

#1297 Approaches to renal response assessment in rare monoclonal immunoglobulin related glomerulopathies

Abstract Background and Aims AL-amyloidosis (AL) and monoclonal immunoglobulin (MIg) deposition disease are common types of MIg-related glomerulopathies (MIgG) and are well-studied including approaches to treatment and hematological and renal responses (RR) assessment. Other rare MIgG comprise very diverse patterns of glomerular injury e.g. proliferative glomerulonephritis with MIg deposition (PGNMID), C3-glomerulopathy, fibrillary glomerulonephritis etc. Although RR defined as decrease in 24 h proteinuria by 30% without kidney function decline was validated only for renal AL it is widely used for MIg deposition disease and rare MIgG without validation. Nevertheless, the best approach to RR assessment in rare MIgG is still unclear. To shed some light on this problem we performed this study. Method We retrospectively analyzed 31 patients with rare MIgG who were treated with clone-specific treatment and had available follow-up (FUP) ≥6 months (mo). The following morphological patterns were diagnosed: PGNMID (n = 9), C3-glomerulopathy (n = 9), thrombotic microangiopathy (n = 5), cryoglobulinemic glomerulonephritis (n = 3), fibrillary glomerulonephritis (n = 3), immunotactoid glomerulonephritis (n = 1) and membranous nephropathy (n = 1). Patients’ baseline parameters are shown on Fig. 1 as well as treatment modalities. Hematological response defined according to currently accepted criteria is demonstrated on Fig. 1. We evaluated two approaches to the RR assessment: 1) at least partial renal response (PR) defined as 24 h proteinuria decreased by 50% from the baseline and &amp;lt;3.5 g, and 2) according to Palladini's criteria for AL (AL-RR) i.e. 24 h proteinuria decreased by 30% from the baseline or &amp;lt;0.5 g. Both RR were considered as achieved only in the absence of estimated glomerular filtration rate (eGFR) decline &amp;gt;25%. Time points for RR assessment were 6, 12 and 24 mo from the clone-specific treatment initiation. Renal outcome was estimated as initiation of renal replacement therapy or eGFR &amp;lt;15 ml/min/1.73 m2 at the end of follow-up. Death-censored renal survival was analyzed by the Kaplan-Meier method. Cox regression analysis was applied to determine which RR was independently associated with long-term kidney outcome. P-value was assumed at &amp;lt;0.05. Median FUP was 19 (7; 50) mo. FUP ≥12 and ≥24 mo were available in 26 and 17 patients, respectively. Results Total number of patients who achieved AL-RR at any RR assessment time point was 22 (71%). At 6, 12 and 24 mo the achievement of AL-RR was registered in 17, 16 and 10 patients, respectively. PR cumulatively was achieved in 19 (61%) patients: at time points of 6, 12, and 24 mo it was registered in 14, 14 and 9 cases, respectively. The 5-year cumulative renal survival in those who had AL-RR was better than in not responders (Fig. 2A). Patients who ever achieved PR had better cumulative renal survival compared with patients with no renal remission (Fig. 2B). In univariate Cox regression analysis the achievement of AL-RR (Exp(β) 0.158 (95% CI 0.03; 0.819)) was associated with renal outcome as well as the achievement of PR (Exp(β) 0.074 (95% CI 0.09; 0.626)). In multivariate Cox regression model adjusted for eGFR at the time of kidney biopsy AL-RR vs no response was estimated as an independent predictor of renal long-term prognosis (Exp(β) 0.082 (95% CI 0.009; 0.725)) as well as eGFR (Exp(β) 0.89 (95% CI 0.821; 0.985)). The only independent predictor of renal outcome in the model including eGFR at the time of kidney biopsy (Exp(β) 0.85 (95% CI 0.72; 0.99), p = 0.05) was PR (Exp(β) 0.011 (95% CI 0; 0.547), p = 0.021). Conclusion The classical concept of complete and partial renal remission seems to be more appropriate for rare MIgG and requires further validation studies.

#831 Associations of quality of life with hospitalization for infection and subsequent death in hemodialysis patients: Osaka Dialysis Complication Study

Abstract Background and Aims Health-related quality of life (HRQOL) as self-reported health status is known to predict mortality in hemodialysis (HD) patients. Infection is one of the major causes for death in those patients, although limited studies have examined possible associations of HRQOL with infection-related outcomes. In the present study, we examined the associations of HRQOL scores with all-cause mortality, hospitalization for infection, and subsequent death in HD patients. Method Patients for this study were selected from the Osaka Dialysis Complication Study (ODCS) which is a prospective cohort study from 2012 to 2017 including a total of 1696 HD patients. HRQOL was assessed by Medical Outcomes Study short form 36 (SF-36) questionnaire to determine scores of the physical component summary (PCS) and the mental component summary (MCS) at baseline, and patients were divided into tertiles of them. The key outcomes were all-cause mortality, hospitalization for infection, and subsequent death after infection. Association was analyzed with Cox proportional hazards models or Fine-Gray models to estimate hazard ratios (HRs) with the highest tertile of PCS or MCS (T3) as referent. Models were unadjusted and adjusted for potential confounders including major demographic factors, traditional cardiovascular risk factors, and the factors related to chronic kidney disease-mineral and bone disorder (CKD-MBD), protein energy wasting and inflammation, and renal anemia. Results We analyzed data from 1464 patients, and we identified 384 all-cause deaths, 321 hospitalizations for infections, and 143 subsequent deaths following infection. Risk of all-cause death was the highest in the lowest PCS tertile in unadjusted model, and this association remained significant in multivariable-adjusted models. In addition, a lower PCS was significantly predictive of a higher risk of both hospitalization for infection in models unadjusted and adjusted for demographic variables, but not significant in a model adjusted for all confounders. However, risk of death after hospitalization for infection was significantly higher in the lowest PCS tertile in unadjusted and in multivariable-adjusted models, compared with the highest PCS tertile. In contrast, MCS was not associated with all-cause mortality, hospitalization for infection, or death following hospitalization for infection. Conclusion A low PCS was associated with both hospitalization for infection and subsequent death after infection in HD patients, but it was more closely associated with the latter. This study revealed that HRQOL, particularly its physical component, is an independent predictor of infection-related outcomes in this population.

Retention rate of vagus nerve stimulation for the treatment of drug-resistant epilepsy: A single-centre, retrospective study.

The aim of this single-centre, retrospective, observational study was to evaluate long-term effectiveness of vagus nerve stimulation (VNS) in drug-resistant epilepsy (DRE) by using retention rate as a surrogate measure for seizure reduction. We included all patients with DRE, treated at the adult neurology department of the University Hospitals Leuven and who started VNS therapy from January 1, 1994, until May 1, 2021, with follow-up data cutoff on January 1, 2023. Retention rate of VNS was defined as the percentage of patients who maintain VNS at established time points. We estimated cumulative retention rate and battery replacement rate and correlated these with seizure reduction, using Kaplan-Meier analysis. Statistical analysis of potential predictors of VNS outcome (age, sex and epilepsy duration at implantation) was performed using mono- and multivariate analyses. VNS was started in 110 patients with DRE, with a mean follow-up of 8.7 years (SD 6.5). VNS was discontinued in 55 patients (50%), with ineffectiveness as the main reason for discontinuation (98%). The battery was replaced at least once in 42 patients (38%). Estimated retention rates were 70%, 52%, 45% and 33% after 5, 10, 15 and 20 years, respectively. Estimated first battery replacement rates were 16%, 42% and 47% after 5, 10 and 15 years, respectively. Both estimates showed a statistically significant correlation with seizure reduction. No independent predictors of long-term outcome of VNS were found. This is the first long-term study using retention rate of VNS to assess effectiveness. VNS is a well-tolerated therapy, but retention rates decline with long follow-up.

Hypoperfusion index ratio and pretreatment with intravenous thrombolysis are independent predictors of good functional outcome in acute ischemic stroke patients with large vessel occlusion treated with acute reperfusion therapies.

We aimed to investigate the performance of several neuroimaging markers provided by perfusion imaging of Acute Ischemic Stroke (AIS) patients with large vessel occlusion (LVO) in order to predict clinical outcomes following reperfusion treatments. We prospectively evaluated consecutive AIS patients with LVO who were treated with reperfusion therapies, during a six-year period. In order to compare patients with good (mRS scores 0-2) and poor (mRS scores 3-6) functional outcomes, data regarding clinical characteristics, the Alberta Stroke Programme Early Computed Tomography Score (ASPECTS) based on unenhanced computed tomography (CT), CT angiography collateral status and perfusion parameters including ischemic core, hypoperfusion volume, mismatch volume between core and penumbra, Tmax > 10s volume, CBV index and the Hypoperfusion Index Ratio (HIR) were assessed. A total of 84 acute stroke patients with LVO who met all the inclusion criteria were enrolled. In multivariable logistic regression models increasing age (odds ratio [OR]: 0.93; 95%CI: 0.88-0.96, p = 0.001), lower admission National Institute of Health Stroke Scale (NIHSS)-score (OR: 0.88; 95%CI: 0.80-0.95, p = 0.004), pretreatment with intravenous thrombolysis (OR: 3.83; 95%CI: 1.29-12.49, p = 0.019) and HIR (OR:0.36; 95%CI: 0.10-0.95, p = 0.042) were independent predictors of good functional outcome at 3months. The initial univariable associations between HIR and higher likelihood for symptomatic intracranial hemorrhage (sICH) and parenchymal hematoma type 2 (PH2) were attenuated in multivariable analyses failing to reach statistical significance. Our pilot observational study of unselected AIS patients with LVO treated with reperfusion therapies demonstrated that pre-treatment low HIR in perfusion imaging and IVT were associated with better functional outcomes.

Prognostic Impact of CYP2C19 Genotypes on Long-Term Clinical Outcomes in Older Patients After Percutaneous Coronary Intervention.

Carriers of CYP2C19 loss-of-function alleles have increased adverse events after percutaneous coronary intervention, but limited data are available for older patients. We aimed to evaluate the prognostic impact of CYP2C19 genotypes on clinical outcomes in older patients after percutaneous coronary intervention. The study included 1201 older patients (aged ≥75 years) who underwent percutaneous coronary intervention and received clopidogrel-based dual antiplatelet therapy in South Korea. Patients were grouped on the basis of CYP2C19 genotypes. The primary outcome was 3-year major adverse cardiac events, defined as a composite of cardiac death, myocardial infarction, and stent thrombosis. Older patients were grouped into 3 groups: normal metabolizer (36.6%), intermediate metabolizer (48.1%), and poor metabolizer (15.2%). The occurrence of the primary outcome was significantly different among the groups (3.1, 7.0, and 6.2% in the normal metabolizer, intermediate metabolizer, and poor metabolizer groups, respectively; P=0.02). The incidence rate of all-cause death at 3 years was greater in the intermediate metabolizer and poor metabolizer groups (8.1% and 9.2%, respectively) compared with that in the normal metabolizer group (3.5%, P=0.03) without significant differences in major bleeding. In the multivariable analysis, the intermediate metabolizer and poor metabolizer groups were independent predictors of 3-year clinical outcomes. In older patients, the presence of any CYP2C19 loss-of-function allele was found to be predictive of a higher incidence of major adverse cardiac events within 3 years following percutaneous coronary intervention. This finding suggests a need for further investigation into an optimal antiplatelet strategy for older patients. URL: https://clinicaltrials.gov. Identifier: NCT04734028.

THE COMPLEX WORLD OF NON CRITICAL CORONARY ARTERIES DISEASE

Abstract Background and Aim Acute coronary syndrome (ACS) with non–critical coronary arteries represents a major diagnostic, therapeutic and prognostic challenge for clinicians. The aim was to compare clinical–anamnestic characteristics and assess the prognosis of three cohorts with ACS with non–critical coronary arteries i.e. Myocardial Infarction with Nonobstructive Coronary Arteries (MINOCA), type 2 myocardial infarction (MI) and Takotsubo syndrome (TTS). Methods In this single center observational study, 18223 patients who underwent coronary angiography between 2005 and 2022 were retrospectively analyzed. The final cohort included 676 patients with initial presentation as NSTEMI (301 MINOCA, 237 type 2 MI and 138 TTS). Results The median age was 68±11, with the TTS population being the oldest (72±10, p&amp;lt;0.01), presenting greater hypotension (p&amp;lt;0.01), tachycardia (p&amp;lt;0.01), and fewer cardiovascular risk factors, such as diabetes (p&amp;lt;0.01) and hypertension (p&amp;lt;0.01). The TTS cohort had worse LVEF on admission (p&amp;lt;0.01) and on discharge (p&amp;lt;0.01) (Fig. 1). At Kaplan–Meier analysis, patients with type 2 MI were more prone to the composite endpoint, while the TTS group was less likely (p&amp;lt;0.01) (Fig. 2). In the overall cohort, ACEi/ARB therapy on admission was an independent predictor of the composite endpoint (HR: 1.58;p=0.01), while dual antiplatelet therapy (DAPT) (HR: 0.59;p=0.01) and statin (HR: 0.71;p=0.03) at discharge were protective. After stratification according to diagnosis, ACEi/ARB therapy remained a negative predictor only in the type 2 MI cohort (HR: 2.03;p=0.01) as well as beta–blocker therapy at admission in TTS (HR: 2.97;p=0.03), while statin therapy remained protective in the MINOCA (HR: 0.51;p=0.01) and DAPT therapy in the TTS group (HR: 0.21;p=0.04) at discharge. Although a substantial number of patients with all three diagnoses achieved the endpoint, the multivariable Cox regression analysis indicated that type 2 MI, in addition to older age, male gender, worse LVEF, and anemia, is an independent factor for worse outcomes (Fig. 3). Conclusions Among all cohorts, T2 MI were associated with worse outcome. The use of DAPT in TTS and Statins in the MINOCA group showed a protective role. Since the TTS population was more compromised, BB use in the ADHF phase of TTS could predict a poorer outcome as much as ACEI/ARB use at admission could be a marker of greater early LV impairment of the T2 MI cohort, which was an independent predictor for worst outcome.

Sociodemographic Disparities and Postoperative Outcomes Following Cranial Vault Remodeling for Craniosynostosis: Analysis of the 2012 to 2021 NSQIP-Pediatric Database.

The objective of this study was to assess whether race and ethnicity are independent predictors of inferior postoperative clinical outcomes, including increased complication rates, extended length of stay (LOS), and unplanned 30-day readmission following cranial vault repair for craniosynostosis. A retrospective cohort study was performed using the American College of Surgeons National Surgical Quality Improvement Program-Pediatric database. Pediatric patients under 2 years of age undergoing cranial vault repair for craniosynostosis between 2012 and 2021 were identified using the International Classification of Diseases-9/10 and Current Procedural Terminology codes. Patients were dichotomized into 4 cohorts: non-Hispanic White (NHW), non-Hispanic Black (NHB), Hispanic, and other. Only patients with available race and ethnicity data were included in this study. Patient demographics, comorbidities, surgical variables, postoperative adverse events, and hospital resource utilization were assessed. Multivariate logistic regression analysis was used to assess the impact of race on complications, extended LOS, and unplanned readmissions. In our cohort of 7764 patients, 72.80% were NHW, 8.44% were NHB, 15.10% were Hispanic, and 3.67% were categorized as "other." Age was significantly different between the 4 cohorts (P<0.001); NHB patients were the oldest, with an average age of 327.69±174.57 days old. Non-Hispanic White experienced the least adverse events while NHB experienced the most (P=0.01). Total operative time and hospital LOS were shorter for NHW patients (P<0.001 and P<0.001, respectively). Rates of unplanned 30-day readmission, unplanned reoperation, and 30-day mortality did not differ significantly between the 4 cohorts. On multivariate analysis, race was found to be an independent predictor of extended LOS [NHB: adjusted odds ratio: 1.30 (1.04-1.62), P=0.021; other: 2.28 (1.69-3.04), P=0.005], but not of complications or readmission. Our study demonstrates that racial and ethnic disparities exist among patients undergoing cranial vault reconstruction for craniosynostosis. These disparities, in part, may be due to delayed age of presentation among non-Hispanic, non-White patients. Further investigations to elucidate the underlying causes of these disparities are necessary to address gaps in access to care and provide equitable health care to at-risk populations.

Defining the correlates of lymphopenia and independent predictors of poor clinical outcome in adults hospitalized with COVID-19 in Australia

Lymphopenia is a common feature of acute COVID-19 and is associated with increased disease severity and 30-day mortality. Here we aim to define the demographic and clinical characteristics that correlate with lymphopenia in COVID-19 and determine if lymphopenia is an independent predictor of poor clinical outcome. We analysed the ENTER-COVID (Epidemiology of hospitalized in-patient admissions following planned introduction of Epidemic SARS-CoV-2 to highly vaccinated COVID-19 naïve population) dataset of adults (N = 811) admitted for COVID-19 treatment in South Australia in a retrospective registry study, categorizing them as (a) lymphopenic (lymphocyte count < 1 × 109/L) or (b) non-lymphopenic at hospital admission. Comorbidities and laboratory parameters were compared between groups. Multiple regression analysis was performed using a linear or logistic model. Intensive care unit (ICU) patients and non-survivors exhibited lower median lymphocyte counts than non-ICU patients and survivors respectively. Univariate analysis revealed that low lymphocyte counts associated with hypertension and correlated with haemoglobin, platelet count and negatively correlated with urea, creatinine, bilirubin, and aspartate aminotransferase (AST). Multivariate analysis identified age, male, haemoglobin, platelet count, diabetes, creatinine, bilirubin, alanine transaminase, c-reactive protein (CRP) and lactate dehydrogenase (LDH) as independent predictors of poor clinical outcome in COVID-19, while lymphopenia did not emerge as a significant predictor.

CatLet score and clinical CatLet score as predictors of long-term outcomes in patients with acute myocardial infarction presenting later than 12 hours from symptom onset

Background Our recently developed C oronary A rtery T ree description and L esion E valua T ion (CatLet) angiographic scoring system is unique in its description of the variability in the coronary anatomy, the degree of stenosis of a diseased coronary artery, and its subtended myocardial territory, and can be utilized to predict clinical outcomes for patients with acute myocardial infarction (AMI) presenting ≤12 h after symptom onset. The current study aimed to assess whether the Clinical CatLet score (CCS), as compared with CatLet score (CS), better predicted clinical outcomes for AMI patients presenting >12 h after symptom onset. Methods CS was calculated in 1018 consecutive AMI patients enrolled in a retrospective registry. CCS was calculated by multiplying CS by the ACEF I score (age, creatinine, and left ventricular ejection fraction). Primary endpoint was major adverse cardiac events (MACEs) at 4-year-follow-up, a composite of cardiac death, myocardial infarction, and ischemia-driven revascularization. Results Over a 4-year follow-up period, both scores were independent predictors of clinical outcomes after adjustment for a broad spectrum of risk factors. Areas-under-the-curve (AUCs) for CS and CCS were 0.72(0.68–0.75) and 0.75(0.71–0.78) for MACEs; 0.68(0.63–0.73) and 0.78(0.74–0.83) for all-cause death; 0.73(0.68–0.79) and 0.83(0.79–0.88) for cardiac death; and 0.69(0.64–0.73) and 0.75(0.7–0.79) for myocardial infarction; and 0.66(0.61–0.7) and 0.63(0.58–0.68) for revascularization, respectively. CCS performed better than CS in terms of the above-mentioned outcome predictions, as confirmed by the net reclassification and integrated discrimination indices. Conclusions CCS was better than CS to be able to risk-stratify long-term outcomes in AMI patients presenting >12 h after symptom onset. These findings have indicated that both anatomic and clinical variables should be considered in decision-making on management of patients with AMI presenting later.

Body mass index and long-term survival following acute pulmonary embolism: insights from machine learning models

Abstract Funding Acknowledgements None. Introduction Body mass index (BMI) has been associated with long-term survival in the setting of acute pulmonary embolism (PE) [1,2]. The non-linear pattern of this association proves to be challenging for frequentist statistical analyses. Contemporary machine learning models offer superior handling capabilities of datasets with non-linear data distributions. Purpose To examine the predictive power of BMI expressed as a continuous variable in a dataset of patients with pulmonary embolism (PE) using the extreme gradient boosting (XGBoost) machine learning framework. Methods All consecutive patients with confirmed PE admitted to the two tertiary teaching Clinical Hospitals in the metropolitan area from November 2013 until November 2018 were included in the study. The diagnosis was established by multislice computed tomography angiography. Machine learning models were investigated using the LightGBM variant of XGBoost. We allocated 80% of the dataset for model training and the remaining 20% for testing. Two models were tested: (1) a model with 20 variables tailored according to the Cox proportional hazards model in the initial publication; (2) a model with 11 independent predictors of outcome. Results The study population is described in detail in previous publications [1,2]. In brief, a total of 761 patients were included in the study. The population was predominantly female (57.4%), aged 73 (61-81). The median overall follow-up was 675 days (114-1331). There were 335 (44.0%) cases of death recorded at follow-up. A Cox proportional hazards model with 19 covariates significantly predicted death during follow-up (χ2 = 595.5, p&amp;lt;0.001). The first BMI quartile was an independent predictor of death (hazard ratio 1.66, 95% confidence interval 1.31-2.10). However, when expressed as a continuous variable, BMI failed to enter the model. In both XGBoost models, BMI expressed as a continuous variable proved to be a feature with high predictive power, second only to pulmonary embolism severity index score (Figure 1 and 2). The models showed high accuracy, with an area under curve of 0.840 and 0.864 respectively. Conclusion In the XGBoost analysis, a machine learning framework with superior handling of non-linear data, BMI expressed as a continuous variable emerged as the second strongest predictor of outcome among 761 PE patients.Figure 1Figure 2