Citations

AbstractBackgroundA hallmark of Alzheimer’s disease is amyloid‐β (Aβ) deposition in the brain parenchyma as senile plaques which Aß frequently accompanies in the cerebral vasculature as cerebral amyloid angiopathy (CAA). Previous studies demonstrated that the cerebrovascular system is essential for Aβ clearance and interactions exist between cerebrovascular disease and AD. Neuroimaging data, including measures on small vessel disease, amyloid deposits, and microhemorrhages (MCH), can reflect both cerebrovascular disease and AD pathology, thereby serving as intermediate phenotypes of both conditions. We aim to identify genes and co‐expression networks in blood associated with these neuroimaging endophenotypes and the biological pathways enriched in these perturbed transcriptional networks.MethodWe conducted differential gene expression and Weighted Gene Co‐Expression Network analyses (WGCNA) on blood RNA sequencing data of 407 participants from the longitudinally followed Mayo Clinic Study of Aging cohort. The neuroimaging phenotypes include MCH, infarction, and amyloid deposits measured by Pittsburgh compound B positron emission tomography (PiB PET).ResultWGCNA analysis showed a nominally significant association (p<0.05) between several module eigengenes (MEs) and MCH and PiB PET. One module, M42, remained significantly associated with PiB PET after Bonferroni correction for all 43 modules tested. Pathway enrichment analysis of M42 identified two significant pathways (FDR‐adjusted p<0.05) including phosphodiesterase I activity and IgE binding. These pathways contain genes such as MS4A2 encoding the high‐affinity IgE receptor involved in the immune response. Similarly, ENPP2 in the phosphodiesterase I activity pathway represents an additional candidate gene previously implicated in Alzheimer’s disease.ConclusionWe generated co‐expression networks and identified one network module with a statistically significant association between brain amyloid deposits and blood transcriptome data. Further investigations of this network and its enriched pathways are necessary to understand their roles in amyloidosis, CAA, and neurodegeneration. Future studies will include seeking replication of these results in other datasets. Such studies can help elucidate the biological mechanisms of pathogenesis of cerebrovascular damage and amyloid deposits. In addition, in a clinical setting, blood levels of transcripts discovered in this study may serve as predictive or diagnostic biomarkers with mechanistic implications.

Background: While spontaneous coronary artery dissection (SCAD) patients can present with ventricular arrhythmias (VAs), the in-hospital outcomes among these patients are not well-established. Objective: This study aimed to analyze the in-hospital outcomes of patients with SCAD and concurrent VAs, and to determine the predictors of VAs occurrence in this population. Methods: Using the Nationwide Readmissions Database, our study included patients aged 18 years or older who had SCAD between 2017 and 2020. We categorized the cohort into two groups depending on the presence of VAs during hospitalization. The in-hospital outcomes were assessed between two groups. Through multivariable analysis, we further analyzed the predictors of VAs occurrence among SCAD patients. Results: Our study included 160 (13.45%) SCAD patients with concurrent VAs and 1,030 (86.55%) SCAD patients without concurrent VAs between 2017 and 2020. SCAD patients with concurrent VA were associated with higher rates of early mortality (11.88% vs. 2.04%, p<0.01), prolonged index hospital stay (≥7 days) (31.25% vs. 12.82%, p<0.01), and non-home discharge (21.88% vs. 6.50%, p<0.01). The length of hospital stay was longer in the SCAD with concurrent VAs group (6.93 days vs. 3.73 days, p<0.01), and the median cumulative cost of hospitalization was also higher in this group ($31,450 vs. $14,664, p<0.01). SCAD with concurrent VAs patients also had poorer in-hospital adverse events. In multivariable analysis, the independent predictors for VAs occurrence among SCAD patients were chronic liver disease (aOR: 2.18; 95% CI: 1.15- 4.12, p=0.02) and heart failure (aOR: 3.40; 95%CI: 2.30- 5.02, p<0.01). Conclusion: Ventricular arrhythmias among SCAD patients were associated with poorer in-hospital outcomes. Heart failure and chronic liver disease were the predictors of VAs in SCAD patients. This highlights the importance of closely monitor and aggressive VAs management among these high-risk patients.

Background: Non-Hodgkin lymphoma (NHL) survivors are at increased risks of cardiovascular disease related death (CVD) compared to the general population. Objective: This study sought to determine the longitudinal trends in mortality attributed to CVD with comorbid NHL by race, sex, and geographic location. Methods: We queried the Centers for Disease Control and Prevention's Wide-Ranging Online Data for Epidemiologic Research database among patients aged 18 and above from 1999 to 2020. Patients were identified when the primary causes of death were ischemic heart diseases (ICD 10 I20-I25), cerebrovascular diseases (I60-I69), or hypertensive disease (I10-I15), and NHL (C82-C85) was a contributing cause of death. We calculated age-adjusted mortality rates (AAMRs) per 1,000,000 individuals and determined the trends over time by estimating the annual percent change using the Joinpoint regression program. Results: In the 22-year study period, a total of 22,778 CVD with comorbid NHL were identified. Overall, there was a significant decrease in annual trends for the AAMRs of CVD from 6.91 per 1,000,000 individuals in 1999 to 4.12 per 1,000,000 individuals in 2020 (p<0.05), with an annual percent decrease of 3.3. Overall, men recorded a higher AAMRs compared to women (6.76 vs 3.45, p<0.05). When stratified by race, White individuals had the highest AAMRs (5.07), while the AAMRs for American African, Asian, American Indian individuals were 3.01, 2.77, and 2.48 per 1,000,000 individuals respectively. The AAMRs were higher in the rural region than in the urban region (4.97 vs 4.78, p<0.05). Among all consensus regions, South region had the highest AAMRs. Conclusion: In conclusion, our study revealed a significant decrease in cardiovascular disease related deaths with comorbid NHL over the past two decades. It provides valuable insights into the effectiveness of management of comorbid CVD or CVD risk factors in patients with NHL.

Background: Catheter ablation for ventricular tachycardia (VT) has been increasingly performed. While it is estimated that 42% of adults in the United States are obese, the impact of obesity on VT ablation procedures remains unclear. Objective: This study aimed to evaluate the procedural outcomes and 30-day readmission among non-obese and obese patients who underwent catheter ablation of VT. Method: Using the Nationwide Readmissions Database, our study included patients aged 18 years or older who underwent catheter ablation for VT between 2017 and 2020. The study cohort was stratified into non-obese (BMI < 30kg/m 2 ) and obese (BMI ≥ 30kg/m 2 ). The in-hospital procedural outcome and 30-day readmission were analyzed between these groups. Results: Our study included a total of 835 obese patients (19.7%) and 3393 non-obese patients (80.3%). Obese group had a higher rate of prolonged length of stay (>7 days) (37.6% vs 31.2%, p<0.01) and a higher cost of hospitalization ($39 983 vs $37 015, p<0.01). Overall, there were no significant differences in early mortality (4.5% vs 3.8%, p=0.45). Apart from increased vascular complications in the obese group (1.8% vs 0.9%, p=0.03), there were no significant differences in other procedural complications between both groups. There were no significant differences in 30-day readmission rates between obese and non-obese groups (15.5% vs 14.1%, p=0.38). Additional analysis performed in the obese group revealed a non-significant decreasing trend in early mortality rate post-procedurally (5.4% to 4.8%, P trend = 0.66). On multivariable analysis, heart failure was associated with a higher risk of 30-day readmission in obese patients (OR: 2.00; 95% CI: 1.01-3.99; p=0.05). Conclusion: Our study suggests that catheter ablation for VT can be performed relatively safely in obese patients without significant differences in 30-day mortality and readmission outcomes. Patients should not be excluded from VT ablation on the basis of obesity.

Background: Despite the optimal efficacy of catheter ablation for ventricular tachycardia (VT), recurrence of VT can occur post-procedurally. However, data on the high-risk population for VT recurrence and the in-hospital outcomes remain scarce. Objective: This study aimed to determine the predictors of 30-day readmission for recurrent VT after catheter ablation of VT and assess the in-hospital outcomes. Method: Using the all-payer, nationally representative Nationwide Readmissions Database, we identified the patients aged ≥18 years who underwent catheter ablation for VT and were readmitted within 30 days because of recurrent VT from 2017 to 2020. We performed unweighted univariable and multivariable analyses to determine the outcomes and to identify the patient and hospital variables that were predictive of 30-day readmissions for recurrent VT. A p-value of <0.05 is considered statistically significant. Results: In our analysis, a total of 4,102 patients were discharged alive after VT ablation, of which 278 (6.8%) were readmitted within 30 days for recurrent VT. Recurrent VT was also the most common cause of 30-day readmission (47.7%, n=278/583). Compared to non-recurrent VT readmission, readmission due to recurrent VT had higher mortality during rehospitalization (7.55% vs 3.72%, p<0.01) and higher cumulative hospitalization cost ($57584 vs $37846, p<0.01). Via multivariable analysis, congestive heart failure (aOR: 1.84; 95% CI: 1.07-3.17; P=0.03) and non-elective index admissions (aOR: 1.88; 95% CI: 1.32-2.68; P<0.01) were the independent predictors of 30-day readmission for recurrent VT. Conclusion: Recurrent VT was the most common cause of 30-day readmission following VT ablation. Congestive heart failure and non-elective index admissions were the independent predictors of 30-day readmissions for recurrent VT. These highlight the importance of further research in ablation strategies to improve the efficacy of VT ablation.

Background: Catheter ablation for ventricular tachycardia (VT) has been increasingly performed over the past decades. However, the real-world data on the safety profile of this procedure among elderly patients is limited. Objective: This study aimed to evaluate the procedural outcomes and 30-day readmission among those aged 18-64 years versus those aged ≥65 years who underwent catheter ablation of VT. Method: Using the all-payer, nationally representative Nationwide Readmissions Database, our study included patients aged 18 years or older who underwent VT catheter ablation between 2017 and 2020. We divided the patients into non-elderly (18-64 years old) and elderly age groups (≥65 years old). We then analyzed the in-hospital procedural outcome and 30-day readmission between these groups. Results: Our study included 2075 (49.1%) non-elderly patients and 2153 (50.9%) elderly patients who underwent VT ablation. Following the procedure, elderly patients had significantly higher rates of prolonged index hospitalization (≥7 days) (35.5% vs 29.3%, p<0.01), non-home discharge (13.4% vs 6.0%, p<0.01), 30-day readmission (17.0% vs 11.4%, p<0.01), and early mortality (5.5% v 2.4%, p<0.01). The median cumulative cost of hospitalization was significantly higher in the elder groups ($40,230 vs. $37,612, p ≤0.01). There was no significant difference in the procedural complications between the two groups. Through multivariable analysis, the elderly group was associated with significantly higher odds of early mortality (OR: 7.50; CI 1.86 - 30.31, p=0.01), non-home discharge (OR: 2.41; CI: 1.93 - 3.00, p<0.01) and 30-day readmissions (OR: 1.58; CI 1.32 - 1.89, p<0.01). Conclusion: Our study suggests that elderly patients have poorer in-hospital outcome in early mortality, non-home discharge and 30-day readmissions following catheter ablation for VT. There was no significant difference between elderly and non-elderly groups in the procedural complications.

The scarcity of liver grafts has prompted developments in living donor liver transplantations (LDLT), with previous literature illustrating similar outcomes in recipients compared to deceased donor transplants. However, significant concerns regarding living donor morbidity and mortality have yet to be examined comprehensively. This study aims to provide estimates of the incidence of various outcomes in living liver donors. In this meta-analysis, Medline and Embase were searched from inception to July 2022 for articles assessing the incidence of outcomes in LDLT donors. Complications in the included studies were classified into respective organ systems. Analysis of incidence was conducted using a generalized linear mixed model with Clopper-Pearson intervals. Eighty-seven articles involving 60,829 living liver donors were included. The overall pooled incidence of complications in LDLT donors was 24.7% (CI: 21.6%–28.1%). The incidence of minor complications was 17.3% (CI: 14.7%–20.3%), while the incidence of major complications was lower at 5.5% (CI: 4.5%–6.7%). The overall incidence of donor mortality was 0.06% (CI: 0.0%–0.1%) in 49,027 individuals. Psychological complications (7.6%, CI: 4.9%–11.5%) were the most common among LDLT donors, followed by wound-related (5.2%, CI: 4.4%–6.2%) and respiratory complications (4.9%, CI: 3.8%–6.3%). Conversely, cardiovascular complications had the lowest incidence among the subgroups at 0.8% (CI: 0.4%–1.3%). This study presents the incidence of post-LDLT outcomes in living liver donors, illustrating significant psychological, wound-related, and respiratory complications. While significant advancements in recent decades have contributed towards decreased morbidity in living donors, our findings call for targeted measures and continued efforts to ensure the safety and quality of life of liver donors post-LDLT.

SummaryBackgroundUpadacitinib is an oral, selective Janus kinase inhibitor.AimTo assess the efficacy and safety of upadacitinib in patients with moderate‐to‐severe ulcerative colitis following 16‐week extended induction therapy, and 52‐week maintenance therapy in patients achieving clinical response after 16‐week extended induction therapyMethodsPatients without clinical response to 8 weeks' upadacitinib 45 mg once daily induction therapy in two induction trials were eligible for an additional 8 weeks of therapy. Patients achieving clinical response at Week 16 were subsequently re‐randomised (1:1) to upadacitinib 15 or 30 mg once daily for 52‐week maintenance therapy. Efficacy was assessed at induction Week 16 (integrated) and maintenance Week 52; safety was assessed throughout.ResultsOverall, 127/663 (19.2%) patients did not achieve clinical response to upadacitinib 45 mg at Week 8 and received an additional 8 weeks of therapy; 75/127 (59.1%) subsequently achieved clinical response at Week 16 and entered the maintenance trial. At Week 52, 26.5% of patients receiving upadacitinib 15 mg, and 43.6% receiving 30 mg, achieved clinical remission; efficacy was observed across all other endpoints with both doses. Herpes zoster rates increased with longer duration (16 weeks) of exposure to upadacitinib 45 mg during induction compared with the same population during the first 8 weeks. No other new safety signals were observed, and results are otherwise consistent with the known safety profile of upadacitinib.ConclusionsPatients without clinical response after 8 weeks' upadacitinib 45 mg induction therapy, may benefit from an additional 8 weeks of therapy.Clinical trial registration: NCT02819635; NCT03653026

Colorectal cancer (CRC) is the third leading cause of cancer-related deaths in the United States. Despite the availability of multiple screening options, CRC screening is underutilized. We conducted a survey of patients (n = 2973) who were prescribed the multi-target stool DNA (mt-sDNA) screening test (commercialized as Cologuard ® and manufactured by Exact Sciences Corporation) to understand attitudes and experiences that influence test completion and likelihood of future test completion. Using exploratory factor analyses, we developed three scales: Perceived Effectiveness, Perceived Ease of Use, and Perceived Comfort.