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Recent evidence supports a link between increased TDP-43 burden and the presence of an APOE4 gene allele in Alzheimer's disease (AD); however, it is difficult to conclude the direct effect of APOE on TDP-43 pathology due to the presence of mixed AD pathologies. The goal of this study is to address how APOE isoforms impact TDP-43 pathology and related neurodegeneration in the absence of typical AD pathologies.We overexpressed human TDP-43 via viral transduction in humanized APOE2, APOE3, APOE4 mice, and murine Apoe-knockout (Apoe-KO) mice. Behavior tests were performed across ages. Animals were harvested at 11 months of age and TDP-43 overexpression-related neurodegeneration and gliosis were assessed. To further address the human relevance, we analyzed the association of APOE with TDP-43 pathology in 160 postmortem brains from autopsy-confirmed amyotrophic lateral sclerosis (ALS) and frontotemporal lobar degeneration with motor neuron disease (FTLD-MND) in the Mayo Clinic Brain Bank.We found that TDP-43 overexpression induced motor function deficits, neuronal loss, and gliosis in the motor cortex, especially in APOE2 mice, with much milder or absent effects in APOE3, APOE4, or Apoe-KO mice. In the motor cortex of the ALS and FTLD-MND postmortem human brains, we found that the APOE2 allele was associated with more severe TDP-43-positive dystrophic neurites.Our data suggest a genotype-specific effect of APOE on TDP-43 proteinopathy and neurodegeneration in the absence of AD pathology, with the strongest association seen with APOE2. This article is protected by copyright. All rights reserved.

Abdominal arterial calcification (AAC) is common among candidates for kidney transplant. The aim of this study is to correlate AAC score value with post-kidney transplant outcomes.We modified the coronary calcium score by changing the intake data points and used it to quantitate the AAC. We conducted a retrospective clinical study of all adult patients who were transplanted at our center, between 2010 and 2013, and had abdominal computed tomography scan done before transplantation. Outcomes included mortality, pulse pressure (PP) measured by 24 h ambulatory blood pressure monitoring system, and kidney allograft function measured by iothalamate clearance.For each 1000 increase of AAC score value, there is an associated 1.05 increase in the risk of death (95% CI 1.02, 1.08) (p 0.001). Overall median AAC value for all patients was 1784; Kaplan-Meier curve showed reduced survival of all-cause mortality for patients with AAC score value above median and reduced survival among patients with cardiac related mortality. The iothalamate clearance was lower among patients with total AAC score value above the median. Patients with abnormal PP ( 40 or 60 mmHg) had an elevated median AAC score value at 4319.3 (IQR 1210.4, 11097.1) compared to patients with normal PP with AAC score value at 595.9 (IQR 9.9, 2959.9) (p 0.001).We showed an association of AAC with patients' survival and kidney allograft function after kidney transplant. The AAC score value could be used as a risk stratification when patients are considered for kidney transplant.

In the era of “fast-track’ liver transplantation (LT), neuromuscular blockade (NMB) antagonists such as neostigmine or sugammadex are used to achieve the restoration of neuromuscular function. While sugammadex reverses NMB faster than neostigmine, it has been shown to prolong prothrombin time (PT) and activated thromboplastin time (aPTT). However, this agent’s impact on coagulation during LT is not understood. We compare bleeding risk associated with sugammadex versus neostigmine during liver transplantation. This is a single-center, retrospective review of LT patients who received NMB antagonists intraoperatively between 01/01/2015 to 05/31/2018 at Mayo Clinic in Florida. The primary outcomes were postoperative day (POD) 0-1 bleeding events and POD 0 values of aPTT and INR. Total 241 patients were included, with 135 patients in the neostigmine group (NG) and 106 in the sugammadex group (SG). POD 0-1 postoperative bleeding requiring transfusion occurred in 20% of NG versus 10.4% in SG. POD 0-1 re-operation for bleeding occurred in 1.5% in NG vs. 0% in SG. POD 0 mean INR was 2.0±0.4 in both groups. POD 0 mean aPTT was 45.5±7.9 in NG vs. 49.3±9.0 in SG. Our retrospective study suggests that sugammadex is not associated with an increased risk of bleeding compared to neostigmine use.

Distal or calf deep vein thrombosis (DVT) are said to have low rates of propagation, embolization, and recurrence. The objective of this study was to determine outcomes among cancer patients with calf DVT compared to those without cancer. Consecutive patients with ultrasound confirmed acute calf DVT (3/1/2013-8/10/2019) were assessed for venous thromboembolism (VTE) recurrence and bleeding outcomes compared by cancer status. There were 830 patients with isolated calf DVT; 243 with cancer and 587 without cancer. Cancer patients were older (65.9 ± 11.4 vs. 62.0 ± 15.9 years; p = 0.006), with less frequent recent hospitalization (31.7% vs. 48.0%; p 0.001), surgery (30.0% vs. 38.0%; p = 0.03), or trauma (3.7% vs. 19.9%; p 0.001). The four most common cancers included hematologic malignancies (20.6%), lung (11.5%), gastrointestinal (10.3%), and ovarian/GYN (9.1%). Nearly half of patients had metastatic disease (43.8%) and 57% were receiving chemotherapy. VTE recurrence rates were similar for patients with (7.1%) and without cancer (4.0%; p = 0.105). Major bleeding (6.3% vs. 2.3%; p = 0.007) were greater for cancer patients while clinical relevant non major bleeding rates did not differ (7.1% vs. 4.6%; p = 0.159). In this retrospective analysis, cancer patients with calf DVT have similar rates of VTE recurrence but higher major bleeding outcomes compared to patients without cancer.