Citations

Purpose: Studies on outcomes related to endovascular treatment (EVT) in advanced stages of chronic kidney disease (CKD) and end-stage renal disease (ESRD) among hospitalizations with acute limb ischemia (ALI) are limited. Methods: The Nationwide Inpatient Sample was quarried from October 2015 to December 2017 to identify the hospitalizations with ALI and undergoing EVT. The study population was subdivided into 3 groups based on their CKD stages: group 1 (No CKD, stage I, stage II), group 2 (CKD stage III, stage IV), and group 3 (CKD stage V and ESRD). The primary outcome was all-cause in-hospital mortality. Results: A total of 51 995 hospitalizations with ALI undergoing EVT were identified. The in-hospital mortality was significantly higher in group 2 (OR = 1.17; 95% CI 1.04 – 1.32, p=0.009) and group 3 (OR = 3.18; 95% CI 2.74–3.69, p<0.0001) compared with group 1. Odds of minor amputation, vascular complication, atherectomy, and blood transfusion were higher among groups 2 and 3 compared with group 1. Group 2 had higher odds of access site hemorrhage compared with groups 1 and 3, whereas group 3 had higher odds of major amputation, postprocedural infection, and postoperative hemorrhage compared with groups 1 and 2. Besides, groups 2 and 3 had lower odds of discharge to home compared with group 1. Finally, the length of hospital stay and cost of care was significantly higher with the advancing CKD stages. Conclusion: Advanced CKD stages and ESRD are associated with higher mortality, worse in-hospital outcomes and higher resource utilization among ALI hospitalizations undergoing EVT. Clinical Impact Current guidelines are not clear for the optimum first line treatment of acute limb ischemia, especially in patients with advanced kidney disease as compared to normal/mild kidney disease patients. We found that advanced kidney disease is a significant risk factor for worse in-hospital morbidity and mortality. Furthermore, patients with acute limb ischemia and advanced kidney disease is associated with significantly higher resource utilization as compared to patients with normal/mild kidney disease. This study suggests shared decision making between treating physician and patients when considering endovascular therapy for the treatment of acute limb ischemia in patients with advanced kidney disease.

Abstract Extracellular vesicles have emerged as a less-invasive nano-tool for discovering biomarkers of Alzheimer’s disease and related dementia. Here, we analysed different neuron-enriched extracellular vesicles from plasma to predict response and molecular mechanisms of ketogenic diet’s efficacy in mild cognitive impairment participants. The study was a randomized crossover design in which cognitively normal and mild cognitive impairment participants consumed a modified Mediterranean-ketogenic diet or American Heart Association diet for 6 weeks, followed by other diet after washout. L1 cell adhesion molecule, synaptophysin and neural cell adhesion molecule surface markers were used to enrich for neuron-secreted small extracellular vesicles (sEVL1CAM, sEVSYP and sEVNCAM). For the first time, we have presented multiple evidences, including immunogold labelling/transmission electron microscopy, clusters of differentiation 63-ELISA-based assay, confocal microscopy fluorescent images and flow cytometry data confirming the presence of L1 cell adhesion molecule on the surface of sEVL1CAM, validating purity and relative abundance of sEVL1CAM in the plasma. Cargo analysis of sEVL1CAM showed that modified Mediterranean-ketogenic diet intervention reduces amyloid beta 1–42 (50.3%, P = 0.011), p181-tau (34.9%, P = 0.033) and neurofilament light (54.2%, P = 0.020) in mild cognitive impairment participants. Moreover, sEVL1CAMshowed better sensitivity compared with CSF in analysing increased glutamate (6-folds, P &lt; 0.0001) from mild cognitive impairment participants following modified Mediterranean-ketogenic diet intervention. sEVL1CAM characterization also suggested that modified Mediterranean-ketogenic diet differentially targets the expression of various glutamate receptors—glutamate receptor ionotropic NMDA1, glutamate receptor ionotropic NMDA2A, glutamate receptor ionotropic NMDA2B and glutamate receptor ionotropic AMPA type subunit 1. Importantly, these sEVL1CAM measures strongly correlated with corresponding clinical CSF biomarkers (neurogranin, amyloid beta 1–42, neurofilament light and tau). Furthermore, sEVL1CAM were loaded with less advanced glycation endproducts and exhibited anti-inflammatory activity following modified Mediterranean-ketogenic diet intervention. Most importantly, the expression of monocarboxylate transporter 2 on the surface of sEVL1CAM predicted the amyloid beta 1–42 response to modified Mediterranean-ketogenic diet intervention (area under the curve = 0.87, P = 0.0044) and offered a novel screening tool to identify participants responsive to this dietary intervention. Finally, sEVL1CAM, sEVSYP and sEVNCAM showed significantly high concordance in analysing amyloid beta 1–42 (Pearson correlation coefficient ≥ 0.63, P &lt; 0.01) and neurofilament light (Pearson correlation coefficient ≥ 0.49, P &lt; 0.05). Together, small extracellular vesicles in plasma offers promise in assessing the efficacy of dietary/therapeutic intervention against mild cognitive impairment/Alzheimer’s disease.

Purpose. To assess the antiarrhythmic properties of dexmedetomidine in patients in the intensive care unit. Methods. A literature review was conducted with Ovid MEDLINE (R), Cochrane Central Register of Controlled Trials, Cochrane Database of Systematic Reviews, Embase, and Scopus. Study Selection. Randomized controlled trials were included, examining the incidence of ventricular arrhythmias, ventricular tachycardia, or ventricular fibrillation with dexmedetomidine compared to placebo or an alternative sedative agent. For each publication that met the selection criteria, the patient demographics, incidence of arrhythmias, mortality, and adverse events were collected. Data extraction was carried out by two authors independently. Results. We identified 6 out of 126 studies that met the selection criteria for our meta-analysis, all of which focused on the perioperative cardiac surgery period. Patients receiving dexmedetomidine demonstrated a significant reduction of the overall incidence of ventricular arrhythmias (RR 0.35, 95% CI 0.16, 0.76). In particular, dexmedetomidine significantly decreased the risk of ventricular tachycardia compared with control (RR 0.25, 95% CI 0.08, 0.80, I2 0%). Regarding adverse events, dexmedetomidine significantly increased the frequency of bradycardia (RR 2.78 95% CI 2.00, 3.87). However, there was no significant difference in mortality (RR 0.59 95% CI 0.12, 3.02). Conclusion. From this meta-analysis, we report a decreased incidence of ventricular tachycardia with dexmedetomidine in critically ill patients. This result favors the use of dexmedetomidine for its antiarrhythmic properties.

Abstract Background: Atrial fibrillation (AF) is relatively less frequent in younger patients (age<50). Recently, studies have suggested that early restoration of sinus rhythm may lead to improved outcomes compared with rate control. Methods: We included all hospitalized patients between 18 and 50 years with a diagnosis of AF from the Nationwide Readmission Database 2016-2017 from the Healthcare Cost and Utilization Project. Demographic and comorbidity data were collected and analyzed. Outcomes assessed included one-year AF readmission rates, all-cause readmission, ischemic stroke, and all-cause mortality. Subgroup analyses were performed for all demographic and comorbidity variables.Results: Overall, 52,598 patients (medium age 44, interquartile range 38-48, female 25.7%) were included in the study, including 2,146 (4.0%) who underwent catheter ablation for AF. Patients who underwent catheter ablation had a significantly lower rate of readmission for AF or any cause at one year (adjusted hazard ratios (HR) of 0.52 [95% confidence interval (CI): 0.43-0.63] and HR of 0.81 [95% CI: 0.72 - 0.89], respectively). There was no difference in 1-year readmission for stroke or all-cause mortality between the two groups. Subgroup analyses showed a consistent reduction in the risk of AF readmission among major demographic and comorbidity subgroups.Conclusion: Catheter ablation in young patients with AF was associated with a reduction in 1-year AF related and all-cause readmissions. These data merit further prospective investigation for validation.

Introduction: In the last two decades, risk factors, prevalence, and mortality due to coronary artery disease in young adults is on the rise. Hypothesis: Assess the prevalence, trends, and economic burden of ventricular tachycardia (VT) in young adults (18-44 years). Methods: The Nationwide Inpatient Sample was explored for hospitalizations with VT in patients (Age 19-44) between 2005-2018 and divided among 3 groups of the quadrennial period using validated ICD-9 and ICD-10 CM codes. The Pearson chi-square test and Student’s t-test were used for categorical and continuous variables, respectively. We assessed the temporal trends of mortality in VT as well as trends of VT stratified by age, sex, and race by the linear-by-linear association test (Figure 1). Results: Out of 5,156,326 patients were admitted with VT between 2005-2018, 309,636 were in young adults. Among them, 102,433 were admitted between 2005-2009 (mean age 36.1±6.99; 61% male, 58.5% white), 109,591 between 2010-2014 (mean age 35.5±7.16; 59% male, 54.2% white), and 97,495 between 2015-2018 (mean age 35.4±7.00; 60% male, 52.3% white) (p<0.0001). In the young adults with VT, all-cause mortality was 7.37% from 2005-2009, 7.85% from 2010-2014 (6.5% relative increase from 2005-2009), and 8.98% from 2015-2018 (relative increase of 14.4% from 2010-2014) (p<0.0001). Inflation adjusted cost increased over the years [$12,177 in 2005-2009; $13,249 in 2010-2014; $15,807 in 2015-2018; p<0.0001)]. Conclusions: The prevalence of VT in young individuals is rising. VT-related mortality and healthcare utilization costs are on the rise in the study period. VT burden and poor outcomes were notable for Black males. Further studies are required for targeted screening and preventative measures in young adults.

Introduction: Real-world data on the significance of adding a defibrillator to cardiac resynchronization therapy (CRT-D) in patients with nonischemic cardiomyopathy (NICM) are limited. Hypothesis: CRT-D is associated with a lower risk of mortality and heart failure (HF) readmissions compared to CRT-P in NICM. Methods: We identified patients with NICM who underwent CRT-D and CRT without an ICD (CRT-P) by analyzing the nationwide readmission database from October 2015- December 2018 and using appropriate ICD-10 CM codes. Propensity score matching was performed to adjust for the confounders. Kaplan Meier curves were utilized for time to event analysis. Cox proportional hazard regression was used to generate hazard ratios. All-cause mortality at 6 months was the primary outcome whereas readmission due to HF and any other cause at 6 months were defined as secondary outcomes. Results: Post-PSM, 3054 patients with NICM underwent CRT-P, and 2863 patients underwent CRT-D placement. CRT-D did not show any benefit over CRT-P in reducing all-cause mortality at 6 months (2.92% vs. 2.79%, HR: 0.84, 95% CI: 0.61-1.16, p=0.29). Similarly, there was no difference in terms of readmissions due to other causes among both groups of patients (36.25% vs. 31.85%, HR: 0.98, 95% CI: 0.89-1.08, p=0.77). However, patients with CRT-P implantations had a lower risk of HF readmissions compared to the CRT-D group (10.05% vs. 14.25%, HR: 0.67, 95% CI: 0.58-0.79, p<0.0001). Conclusions: The addition of a defibrillator to CRT failed to show a survival benefit in patients with NICM. Moreover, HF readmissions were higher in CRT-D patients compared to CRT-P.

Abstract ALK-positive histiocytosis is a rare subtype of histiocytic neoplasm first described in 2008 in 3 infants with multisystemic disease involving the liver and hematopoietic system. This entity has subsequently been documented in case reports and series to occupy a wider clinicopathologic spectrum with recurrent KIF5B-ALK fusions. The full clinicopathologic and molecular spectra of ALK-positive histiocytosis remain, however, poorly characterized. Here, we describe the largest study of ALK-positive histiocytosis to date, with detailed clinicopathologic data of 39 cases, including 37 cases with confirmed ALK rearrangements. The clinical spectrum comprised distinct clinical phenotypic groups: infants with multisystemic disease with liver and hematopoietic involvement, as originally described (Group 1A: 6/39), other patients with multisystemic disease (Group 1B: 10/39), and patients with single-system disease (Group 2: 23/39). Nineteen patients of the entire cohort (49%) had neurologic involvement (7 and 12 from Groups 1B and 2, respectively). Histology included classic xanthogranuloma features in almost one-third of cases, whereas the majority displayed a more densely cellular, monomorphic appearance without lipidized histiocytes but sometimes more spindled or epithelioid morphology. Neoplastic histiocytes were positive for macrophage markers and often conferred strong expression of phosphorylated extracellular signal-regulated kinase, confirming MAPK pathway activation. KIF5B-ALK fusions were detected in 27 patients, whereas CLTC-ALK, TPM3-ALK, TFG-ALK, EML4-ALK, and DCTN1-ALK fusions were identified in single cases. Robust and durable responses were observed in 11/11 patients treated with ALK inhibition, 10 with neurologic involvement. This study presents the existing clinicopathologic and molecular landscape of ALK-positive histiocytosis and provides guidance for the clinical management of this emerging histiocytic entity.

Introduction: The management of asymptomatic severe aortic stenosis (AS) is controversial and guidelines for the management of the same is not updated based on recently available evidence. Hypothesis: The main objective is to determine the optimal strategy for the management of asymptomatic severe AS between early intervention versus conservative management. Methods: We performed a systematic electronic search of the PubMed and Cochrane databases from the inception of the database to May 31 st , 2020. We used the Mantel Haenszel method with the Paule-Mandel estimator of Tau 2 and Hartung-Knapp adjustment to calculate relative risk (RR) with a 95% confidence interval (CI) and 95% prediction interval (PI). We used P curve analysis to assess publication bias and estimate the true effect of an intervention. All analysis was carried out using R version 3.6.2. Results: A total of seven studies were included in the final analysis, consisting of 1213 patients with early intervention and 2601 patients with conservative management. Early intervention as compared to conservative management was associated with reduced risk of all-cause mortality (RR: 0.32, 95% CI: 0.21-0.48) (Panel A) , cardiac mortality (RR: 0.36, 95% CI: 0.27-0.48) (Panel B) and non-cardiac mortality (RR: 0.40, 95% CI: 0.28-0.56) (Panel C) . There was no difference in the risk of sudden cardiac death (RR: 0.46, 95% CI: 0.15-1.40), stroke (RR: 0.79, 95% CI: 0.17-3.64), myocardial infarction (RR: 0.44, 95% CI: 0.01-16.82) or heart failure hospitalization (RR: 0.18, 95% CI: 0.01-5.29) between the groups. The pooled estimate for all the outcomes was associated with low-moderate heterogeneity. Conclusions: Among asymptomatic severe AS patients, early intervention is associated with reduced mortality without increasing any procedure-related clinical outcomes. Hence, this meta-analysis supports early intervention as opposed to watchful waiting for the management of asymptomatic severe AS.

Introduction: Atrial Fibrillation (AF) has been associated with various behavioral risk factors such as tobacco, alcohol, and/or substance abuse. Hypothesis: The main objective is to describe the national trends and burden of tobacco and substance abuse in AF hospitalizations. Methods: The National Inpatient Sample database from 2007 to 2015 was utilized and the hospitalizations with AF were identified using the international classification of disease, Ninth Revision, Clinical Modification (ICD-9-CM) code 427.31 in the primary diagnosis column. They were stratified into without abuse, tobacco use disorder (TUD), substance use disorder (SUD), alcohol use disorder (AUD), and drug use disorder (DUD). We used the Jonckheere-Terpstra trend test to analyze the trend in this study. Results: Out of 3,631,507 AF hospitalizations, 852,110 (23.46%) had TUD, 1851,170 (5.1%) had SUD, 155,681 (4.29%) had AUD and 42,667 (1.17%) had DUD. The trends of all increased substantially during the study period (Figure) . The prevalence of TUD, SUD, AUD, and DUD was substantially increased across all age groups, races, and gender during the study period. Female sex was associated with lower odds TUD (0.57 (0.56-0.57), P-value <0.001), SUD (0.27 (0.26-0.27), P-value <0.001), AUD (0.22 (0.22-0.22), P-value <0.001), and DUD (0.51 (0.5-0.52), P-value <0.001). Among AF hospitalizations, the black race was associated with higher odds of SUD (1.12 (1.1-1.14), P-value <0.001), and DUD(1.42 (1.38-1.47), P-value <0.001). The younger age group (18-35 years), male, Medicare/Medicaid as primary insurance, and lower socioeconomic status were associated with increased risk of both TUD and SUDs. Conclusions: Tobacco and substance use disorder among hospitalized AF patients in the US mainly affects males, younger individuals, white more than black, and those of lower socioeconomic status which demands the development of preventive strategies to address multilevel influences.