Absence of Obesity Paradox in All-Cause Mortality Among Chinese Patients With an Implantable Cardioverter Defibrillator: A Multicenter Cohort Study

Background: The results of studies on the obesity paradox in all-cause mortality are inconsistent in patients equipped with an implantable cardioverter-defibrillator (ICD). There is a lack of relevant studies on Chinese populations with large sample size. This study aimed to investigate whether the obesity paradox in all-cause mortality is present among the Chinese population with an ICD.Methods: We conducted a retrospective analysis of multicenter data from the Study of Home Monitoring System Safety and Efficacy in Cardiac Implantable Electronic Device–implanted Patients (SUMMIT) registry in China. The outcome was all-cause mortality. The Kaplan–Meier curves, Cox proportional hazards models, and smooth curve fitting were used to investigate the association between body mass index (BMI) and all-cause mortality.Results: After inclusion and exclusion criteria, 970 patients with an ICD were enrolled. After a median follow-up of 5 years (interquartile, 4.1–6.0 years), in 213 (22.0%) patients occurred all-cause mortality. According to the Kaplan–Meier curves and multivariate Cox proportional hazards models, BMI had no significant impact on all-cause mortality, whether as a continuous variable or a categorical variable classified by various BMI categorization criteria. The fully adjusted smoothed curve fit showed a linear relationship between BMI and all-cause mortality (p-value of 0.14 for the non-linearity test), with the curve showing no statistically significant association between BMI and all-cause mortality [per 1 kg/m2 increase in BMI, hazard ratio (HR) 0.97, 95% CI 0.93–1.02, p = 0.2644].Conclusions: The obesity paradox in all-cause mortality was absent in the Chinese patients with an ICD. Prospective studies are needed to further explore this phenomenon.

Amino acids predict prognosis in patients with acute dyspnea

Background To identify amino acids that can predict risk of 90-day mortality in patients with acute dyspnea. Method Plasma levels of nine amino acids were analyzed 663 adult patients admitted to the Emergency Department (ED) with acute dyspnea. Cox proportional hazards models were used to examine the relation between amino acid levels and the risk of 90-day mortality. Result Eighty patients (12.1%) died within 90 days of admission. An “Amino Acid Mortality Risk Score” (AMRS), summing absolute plasma levels of glycine, phenylalanine and valine, demonstrated that among the patients belonging to quartile 1 (Q1) of the AMRS, only 4 patients died, compared to 44 patients in quartile 4. Using Q1 of the AMRS as reference, each increment of 1 SD in the AMRS was associated with a hazard ratio (HR) of 2.15 for 90-day mortality, and the HR was > 9 times higher in Q4. Conclusion Glycine, phenylalanine and valine are associated with a risk of 90-day mortality in patients admitted to the ED for acute dyspnea, suggesting that these amino acids may be useful in risk assessments.

Minimum Threshold of Bariatric Surgical Weight Loss for Initial Diabetes Remission

<b>Objective:</b> There are few studies testing the amount of weight loss necessary to achieve initial remission of type 2 diabetes (T2DM) following bariatric surgery and no published studies using weight loss to predict initial T2DM remission in sleeve gastrectomy (SG) patients. <p><b>Research Design and Methods:</b> Cox proportional hazards models examined the relationship between initial T2DM remission and percent total weight loss (%TWL) after bariatric surgery. Categories of %TWL were included in the model as time-varying covariates. </p> <p><b>Results:</b> Patients (N=5,928) were 73% female, 49.8<u>+</u>10.3 years old, had BMI of 43.8<u>+</u>6.92 kg/m², and 57% had Roux-en-Y gastric bypass (RYGB). Over an average follow-up of 5.9 years, 71% of patients experienced initial remission of their T2DM (mean time to remission 1.0 year). Using 0-5% TWL as the reference group in Cox proportional hazards models, patients were more likely to remit with each 5% increase in TWL until 20% TWL (range from HR=1.97 to 2.92). When categories above >25% TWL were examined, all had a likelihood of initial remission similar to 20-25% TWL. Patients who achieved >20% TWL were more likely to achieve initial T2DM remission than patients with 0-5% TWL, even if they were using insulin at the time of surgery.</p> <p><b>Conclusions: </b>Weight loss after bariatric surgery is strongly associated with initial T2DM remission; however, above a threshold of 20% TWL, rates of initial T2DM remission did not increase substantially. Achieving this threshold is also associated with initial remission even in patients who traditionally experience lower rates of remission, such as patients taking insulin.</p>

Minimum Threshold of Bariatric Surgical Weight Loss for Initial Diabetes Remission

<b>Objective:</b> There are few studies testing the amount of weight loss necessary to achieve initial remission of type 2 diabetes (T2DM) following bariatric surgery and no published studies using weight loss to predict initial T2DM remission in sleeve gastrectomy (SG) patients. <p><b>Research Design and Methods:</b> Cox proportional hazards models examined the relationship between initial T2DM remission and percent total weight loss (%TWL) after bariatric surgery. Categories of %TWL were included in the model as time-varying covariates. </p> <p><b>Results:</b> Patients (N=5,928) were 73% female, 49.8<u>+</u>10.3 years old, had BMI of 43.8<u>+</u>6.92 kg/m², and 57% had Roux-en-Y gastric bypass (RYGB). Over an average follow-up of 5.9 years, 71% of patients experienced initial remission of their T2DM (mean time to remission 1.0 year). Using 0-5% TWL as the reference group in Cox proportional hazards models, patients were more likely to remit with each 5% increase in TWL until 20% TWL (range from HR=1.97 to 2.92). When categories above >25% TWL were examined, all had a likelihood of initial remission similar to 20-25% TWL. Patients who achieved >20% TWL were more likely to achieve initial T2DM remission than patients with 0-5% TWL, even if they were using insulin at the time of surgery.</p> <p><b>Conclusions: </b>Weight loss after bariatric surgery is strongly associated with initial T2DM remission; however, above a threshold of 20% TWL, rates of initial T2DM remission did not increase substantially. Achieving this threshold is also associated with initial remission even in patients who traditionally experience lower rates of remission, such as patients taking insulin.</p>

Identification of a Novel Prognostic Gene Signature From the Immune Cell Infiltration Landscape of Osteosarcoma

Background: The tumor microenvironment (TME) mainly comprises tumor cells and tumor-infiltrating immune cells mixed with stromal components. Latestresearch hasdisplayed that tumor immune cell infiltration (ICI) is associated with the clinical outcome of patients with osteosarcoma (OS). This work aimed to build a gene signature according to ICI in OS for predicting patient outcomes.Methods: The TARGET-OS dataset was used for model training, while the GSE21257 dataset was taken forvalidation. Unsupervised clustering was performed on the training cohort based on the ICI profiles. The Kaplan–Meier estimator and univariate Cox proportional hazards models were used to identify the differentially expressed genes between clusters to preliminarily screen for potential prognostic genes. We incorporated these potential prognostic genes into a LASSO regression analysis and produced a gene signature, which was next assessed with the Kaplan–Meier estimator, Cox proportional hazards models, ROC curves, IAUC, and IBS in the training and validation cohorts. In addition, we compared our signature to previous models. GSEAswere deployed to further study the functional mechanism of the signature. We conducted an analysis of 22 TICsfor identifying the role of TICs in the gene signature’s prognosis ability.Results: Data from the training cohort were used to generate a nine-gene signature. The Kaplan–Meier estimator, Cox proportional hazards models, ROC curves, IAUC, and IBS validated the signature’s capacity and independence in predicting the outcomes of OS patients in the validation cohort. A comparison with previous studies confirmed the superiority of our signature regarding its prognostic ability. Annotation analysis revealed the mechanism related to the gene signature specifically. The immune-infiltration analysis uncoveredkey roles for activated mast cells in the prognosis of OS.Conclusion: We identified a robust nine-gene signature (ZFP90, UHRF2, SELPLG, PLD3, PLCB4, IFNGR1, DLEU2, ATP6V1E1, and ANXA5) that can predict OS outcome precisely and is strongly linked to activated mast cells.

Time to SARS-CoV-2 PCR clearance in immunocompromising conditions: is test-based removal from isolation necessary in severely immunocompromised individuals?

To determine the association between immunosuppression and time to SARS-CoV-2 PCR clearance, we studied 3758 adults re-tested following initial SARS-CoV-2 infection. Cox proportional hazards models demonstrated delayed PCR clearance with older age, multiple comorbidities and solid organ transplant but not by degree of immunocompromise. These findings challenge current retesting practices.

465 Evaluating the Impact of Sleep Disordered Breathing on Adverse Cardiovascular Outcomes After Bariatric Surgery

Introduction Sleep disordered breathing (SDB), including obstructive sleep apnea (OSA) and obesity-associated sleep hypoventilation (OASH), has well-characterized adverse effects on the cardiovascular system and increases morbidity and mortality. Long-term impact on cardiovascular outcomes post-bariatric surgery, however, remains unclear. We hypothesize that patients with SDB have increased frequency of major adverse cardiovascular events (MACE) post-bariatric surgery than those without. Methods Patients undergoing polysomnography (PSG) prior to bariatric surgery at The Cleveland Clinic from 2011–2018 were retrospectively examined and followed up from date of last surgery to 2019, including the perioperative period. Primary predictors include moderate-severe OSA, i.e. apnea hypopnea index(AHI)&gt;15, and OASH, i.e. body mass index (BMI)≥30kg/m2 and either end-tidal CO2≥45mmHg or serum bicarbonate≥27mEq/L. MACE (coronary artery events, cerebrovascular events, heart failure or atrial fibrillation)-free probability was compared using hazard ratios estimated from Cox proportional hazards models on four groups: OASH with moderate-severe OSA (N=492), OASH-only (N=442), moderate-severe OSA-only (N=203), and a reference group without OASH or moderate-severe OSA (N=243). Multivariable Cox proportional hazards models adjusting for age, sex, BMI were fit on MACE survival. Analysis was performed based on an overall significance level of 0.05, using SAS software (version 9.4, Cary, NC). Results The sample comprised 1380 patients: age: 43.5±12 years, BMI: 49±9 kg/m2, 17.7% male, 63.7% White. Risk of MACE across the groups bordered significance (p=0.051). Compared to the reference group, the OASH with moderate-severe OSA group had higher risk of MACE (HR2.53, 95%CI:1.07–6.00,p=0.035). Patients with moderate-severe OSA had higher risk of MACE than those with AHI&lt;15 (HR1.94, 95%CI:1.20–3.13,p=0.007). Patients with severe OSA had higher risk of MACE than those AHI&lt;30 (HR2.01, 95%CI:1.28–3.14,p=0.002). For every 5-unit AHI increase, risk of MACE increased by 6% (HR1.056, 95%CI:1.029–1.084,p&lt;0.001) with slight reduction in point estimates in adjusted models. Conclusion Preliminary data from this largest-to-date sample of systematically phenotyped patients with SDB undergoing bariatric surgery show significant differences in risk of MACE and MACE-free survival mitigated after consideration of obesity. Further investigation to elucidate effect modification by obesity and metabolic factors is needed. Support (if any) Cleveland Clinic Transformative Resource Neuroscience Award

A Machine Learning-Based Model to Predict Survival After Transarterial Chemoembolization for BCLC Stage B Hepatocellular Carcinoma

ObjectiveWe sought to develop and validate a novel prognostic model for predicting survival of patients with Barcelona Clinic Liver Cancer Stages (BCLC) stage B hepatocellular carcinoma (HCC) using a machine learning approach based on random survival forests (RSF).MethodsWe retrospectively analyzed overall survival rates of patients with BCLC stage B HCC using a training (n = 602), internal validation (n = 301), and external validation (n = 343) groups. We extracted twenty-one clinical and biochemical parameters with established strategies for preprocessing, then adopted the RSF classifier for variable selection and model development. We evaluated model performance using the concordance index (c-index) and area under the receiver operator characteristic curves (AUROC).ResultsRSF revealed that five parameters, namely size of the tumor, BCLC-B sub-classification, AFP level, ALB level, and number of lesions, were strong predictors of survival. These were thereafter used for model development. The established model had a c-index of 0.69, whereas AUROC for predicting survival outcomes of the first three years reached 0.72, 0.71, and 0.73, respectively. Additionally, the model had better performance relative to other eight Cox proportional-hazards models, and excellent performance in the subgroup of BCLC-B sub-classification B I and B II stages.ConclusionThe RSF-based model, established herein, can effectively predict survival of patients with BCLC stage B HCC, with better performance than previous Cox proportional hazards models.

The U-Shape Relationship Between Glycated Hemoglobin Level and Long-Term All-Cause Mortality Among Patients With Coronary Artery Disease

Background: Although glycated hemoglobin (HbA1c) was considered as a prognostic factor in some subgroup of coronary artery disease (CAD), the specific relationship between HbA1c and the long-term all-cause death remains controversial in patients with CAD.Methods: The study enrolled 37,596 CAD patients and measured HbAlc at admission in Guangdong Provincial People's Hospital. The patients were divided into 4 groups according to HbAlc level (Quartile 1: HbA1c ≤ 5.7%; Quartile 2: 5.7% &lt; HbA1c ≤ 6.1%; Quartile 3: 6.1% &lt; HbA1c ≤ 6.7%; Quartile 4: HbA1c &gt; 6.7%). The study endpoint was all-cause death. The restricted cubic splines and cox proportional hazards models were used to investigate the association between baseline HbAlc levels and long-term all-cause mortality.Results: The median follow-up was 4 years. The cox proportional hazards models revealed that HbAlc is an independent risk factor in the long-term all-cause mortality. We also found an approximate U-shape association between HbA1c and the risk of mortality, including increased risk of mortality when HbA1c ≤ 5.7% and HbA1c &gt; 6.7% [Compared with Quartile 2, Quartile 1 (HbA1c ≤ 5.7), aHR = 1.13, 95% CI:1.01–1.26, P &lt; 0.05; Quartile 3 (6.1% &lt; HbA1c ≤ 6.7%), aHR = 1.04, 95% CI:0.93–1.17, P =0.49; Quartile 4 (HbA1c &gt; 6.7%), aHR = 1.32, 95% CI:1.19–1.47, P &lt; 0.05].Conclusions: Our study indicated a U-shape relationship between HbA1c and long-term all-cause mortality in CAD patients.