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Abstract Background: Randomized control trials (RCT) have examined the safety and efficacy of direct oral anticoagulants (DOACs) compared to dalteparin in patients with cancer-associated thrombosis (CAT). Increased major bleeding (MB) was seen with edoxaban and increased clinically relevant non-major bleeding (CRNMB) was seen with rivaroxaban and there has been specific concern about increased risk of bleeding among patients with gastrointestinal malignancies (GIM). Results from RCTs comparing apixaban to dalteparin in CAT are pending. Objective: Using the Mayo Clinic VTE registry, we examined the rates of MB, CRNMB, and overall bleeding (MB + CRNMB) in patients with GIM treated with anticoagulation for CAT. Methods: Consecutive patients treated for CAT were enrolled into Mayo Clinic VTE Registry between March 1, 2013 and July 27, 2018 and were followed prospectively for safety and efficacy. Clinical, demographic and imaging data were collected from each participant at the time of study recruitment. Cancer type, stage, and treatment with chemotherapy were recorded. Major and CRNMB events were evaluated at 3-month intervals. Clinical status was assessed by written questionnaire in subjects unable to return at 3 months. Unreturned questionnaires were followed up with a scripted phone interview. The study was approved by Mayo Clinic Institutional Review Board. Results: In the 535 subjects in the registry with CAT, the mean age (64.6 vs. 62.8 years), mean BMI (28.4 vs. 28.8), and percent female (46.4% vs 40.6%) were numerically similar between DOAC and LMWH treatment groups (Table 1). Metastatic disease was present in 53.6% and 60.2% and chemotherapy was being administered in 66.5% and 71.2% of DOAC and LMWH treated patients, respectively. Thrombocytopenia (<100x109/L) at initiation of anticoagulation was present in 6.8% of DOAC treated and 7.5% of LMWH treated patients. Among all cancer patients, 110 (21%) patients had a GIM, 58 (53%) were treated with LWMH and 52 (47%) were treated with a DOAC (42% rivaroxaban or 58% apixaban). In all CAT, the rate of MB was similar in DOAC versus LMWH treated patients (7.8 vs. 5.4 per 100 person-years; HR 1.48, 95% CI 0.72-3.05; Table 2). The rate of CRNMB however, was significantly increased in the DOAC patients compared to LMWH treated patients (6.18 vs. 0.44 per 100 person-years; HR 14.7, 95% CI 1.92, 112.26). In the sub-group of patients with GIM, the rate of MB was non-significantly higher in the DOAC versus LMWH treated patients (11.1 vs. 3.9 per 100 person-years; HR 2.90, 95% CI 0.57, 14.73). In contrast to the overall CAT group, the rate of CRNMB was similar in the DOAC compared to LMWH treated patients (2.10 vs. 1.92 per 100 person-years; HR 1.18, 95% CI 0.07, 20.21). In GIM patients, apixaban compared to rivaroxaban had a numerically higher, but non-significant, rate of major bleeding (23.98 vs. 3.50 per 100 person-years; HR 4.0, 95% CI 0.54-29.87). In the overall group of CAT, the risk of major bleeding was similar between apixaban and rivaroxaban (9.51 vs. 6.77 per 100 person-years). Conclusion: In our registry of subjects with CAT, we identified a significantly increased rate of CRNMB and overall bleeding, but not MB with the use of DOACs. In our data, GIM alone does not appear to account for the increased bleeding risk seen in CAT with DOACs, as we demonstrated no significant increase in major, CRNMB, or overall bleeding compared to LMWH. Direct comparison between apixaban and rivaroxaban was limited by sample size and number of events. Disclosures No relevant conflicts of interest to declare.

INTRODUCTION: Increasing rates of obesity have led to increased numbers of bariatric surgeries performed world-wide. However, some patients do not achieve significant weight loss or develop weight regain following these procedures. Other than estimating the size of the gastric remnant at endoscopy or transaxial imaging, there are limited approaches to quantitate the function of the post-surgical stomach in order to evaluate the disparate weight patterns, or to develop strategy for future treatments, e.g., pharmacotherapy or endoscopic intervention. We hypothesize that altered gastric function in the pre- and post-surgical periods may offer an explanation. Studies performed thus far are difficult to interpret due to heterogeneity in approaches to diagnostic evaluation. The aims of this project were: to assess the feasibility of a new protocol for simultaneous evaluation of gastric accommodation and gastric emptying in the post-bariatric state; and to report normative values in healthy volunteers. METHODS: Methods: We utilized single photon emission computed tomography (SPECT) and gamma scintigraphy to concurrently study postprandial gastric accommodation responses and gastric emptying rates of a limited size meal designed for subsequent use in post-bariatric patients. The standard meal consisted of 1 egg and 1 extra egg yolk scrambled with 111 Indium-activated charcoal (∼130kcal, 9.5g fat) and 120mL 2% milk (130kcal, 4.4g fat). Gastric accommodation was measured using 99m Technetium-SPECT. SPECT imaging was obtained concomitant with gastric emptying of the 111 In-labeled meal. Anterior and posterior scans of the abdomen were obtained for estimating gastric emptying parameters every 15 minute until 90 minutes, and then in 30-minute intervals until 240 minutes or complete emptying. RESULTS: Data on 28/30 healthy volunteers (35.7% men; 67% Caucasian) with completed studies to date are shown in the Table 1 (data presented as mean ± standard deviation). Gastric emptying proportion at 1, 2, and 4 hours, T 1/2 , and gastric volumes including accommodation are graphically depicted in Figures 1 and 2, respectively. CONCLUSION: Discussion: This study has demonstrated feasibility of simultaneous measurement of gastric emptying and accommodation and provides normal values; this sets the stage for future baseline and post-operative scans on patients undergoing sleeve gastrectomy.

BACKGROUND: Patients with cirrhosis are growing older and the overlap between hepatic encephalopathy (HE) & pre-dementia mild cognitive impairment (MCI) is unclear. HE affects visuospatial/psychomotor speed while MCI affects memory. Aim: Determine the performance of elderly cirrhotics on tests for HE and dementia and their impact on quality of life (QOL). METHODS: Outpatient cirrhotics and controls ages 65–95 years were recruited at 4 centers. Subjects had to have MMSE > 25, no current HE or dementia to be eligible. All subjects got tests for HE (psychometric hepatic encephalopathy score, PHES: 5 tests & low score = poor, EncephalApp, OffTime + OnTime, high score = poor) and QOL: Sickness Impact profile (SIP, high score = poor QOL). Cirrhotics also got tests for MCI; RBANS (tests immediate memory, delayed memory, language, visuo-spatial & attention). A neuro-psychologist evaluated results and divided cirrhotics into (A) unimpaired (B) MCI only (C) HE only & (D) (MCI/HE overlap). Demographics, MELD, alcohol etiology, and SIP were compared. Finally, age, gender and education-adjusted norms were created for PHES and EncephalApp based on the controls. Presence of MHE and sensitivity of EncephalApp for MHE diagnosis were evaluated. RESULTS: 109 cirrhotics and 100 non-cirrhotic subjects were included. Demographics/education levels were statistically similar between centers. Controls were older than cirrhotics (74.9 ± 6.6 vs 70.5 ± 4.4, P < 0.05) and had similar education/gender distribution. Despite this, controls performed better than cirrhotics on all tests (PHES 2.9 ± 12.4 vs −4.5 ± +4.5, P < 0.001, EncephalApp Off+On 181.4 ± +71.9 vs 218.2 ± +80.0, P = 0.03) and had a better QOL (SIP total 3.8 ± +7.1 vs 7.9 ± +9.5, Psych 3.3 ± +8.4 vs 7.2 ± +11.1, Phys 3.0 ± +6.2 vs 6.7 ± +9.5, all P < 0.001). Within cirrhosis subgroups (Table 1), demographics, MELD/alc & MMSE were similar. Pts with both MCI/HE had worse cognition on all tests, which translated into a worse QOL compared to other groups. Presence of HE, with/without MCI, contributed towards poor QOL. Norms for PHES/EncephalApp: Adjusting for age, gender & education, 17% (n = 17) patients were positive for MHE on PHES compared to controls. On EncephalApp, 49% (n = 47) patients were positive. AUC for EncephalApp using PHES as the gold standard was 0.86 (0.78-0.95 CI). CONCLUSIONS: In this multi-center study, adjusted norms defining the high sensitivity of EncephalApp to diagnose HE in older individuals were created. Presence of HE regardless of MCI contributed towards poor cognition and QOL in patients >65 years.

Abstract Background and study aim The role of esophageal overtubes in upper gastrointestinal endoscopic suturing is unknown. This study aimed to determine whether overtube use was associated with technical success or adverse events. Patients and methods A retrospective review of consecutive patients who underwent endoscopic suturing for various indications was performed. Results A total of 719 patients underwent endoscopic suturing for various indications, including endoscopic bariatric procedures in 262, stent fixation in 258, defect closure in 190, and hemostasis in nine. An overtube was used in 186 procedures (25.9 %). Technical success was achieved in all cases. Minor mucosal trauma occurred in 15 cases (8.1 %) with use of an overtube, and none without an overtube (P < 0.0001). No full-thickness esophageal perforation or hemorrhage related to overtube use or the suturing device occurred. Conclusions Endoscopic suturing can be performed safely for a variety of indications, including endoscopic bariatric procedures, defect repair, and stent fixation without an esophageal overtube. Minor esophageal mucosal trauma and equipment cost are increased when an overtube is used.

AbstractBackgroundGenetic variation at the microtubule‐associated protein tau locus is associated with clinical parkinsonism. However, it is unclear as to whether microtubule‐associated protein tau H1 subhaplotypes are associated with the burden of neuropathological features of Lewy body disease.ObjectivesTo evaluate associations of microtubule‐associated protein tau haplotypes with severity of Lewy body pathology and markers of SN neuronal loss in Lewy body disease cases.MethodsFive hundred eighty‐five autopsy‐confirmed Lewy body disease cases were included. Six microtubule‐associated protein tau variants (rs1467967, rs242557, rs3785883, rs2471738, rs8070723, and rs7521) were genotyped to define common microtubule‐associated protein tau haplotypes. Lewy body counts were measured in five cortical regions. Ventrolateral and medial SN neuronal loss were assessed semiquantitatively. Nigrostriatal dopaminergic degeneration was quantified by image analysis of tyrosine hydroxylase immunoreactivity in the dorsolateral and ventromedial putamen.ResultsThe common microtubule‐associated protein tau H2 haplotype did not show a strong effect on pathological burden in Lewy body disease. The rare H1j haplotype (1.3%) was significantly associated with a lower dorsolateral putaminal tyrosine hydroxylase immunoreactivity (and therefore greater dopaminergic degeneration) compared to other microtubule‐associated protein tau haplotypes (P = 0.0016). Microtubule‐associated protein tau H1j was also nominally (P ≤ 0.05) associated with a lower ventromedial putaminal tyrosine hydroxylase immunoreactivity (P = 0.010), but this did not survive multiple testing correction. Other nominally significant associations between microtubule‐associated protein tau H1 subhaplotypes and neuropathological outcomes were observed.ConclusionsA rare microtubule‐associated protein tau H1 subhaplotype (H1j) may be associated with more severe putaminal dopaminergic degeneration in Lewy body disease cases. Microtubule‐associated protein tau H1j has been associated previously with an increased risk of PD, and therefore our exploratory findings provide insight into the mechanism by which H1j modulates PD risk. © 2019 International Parkinson and Movement Disorder Society

OBJECTIVES: Nosocomial infections (NIs) can be a major cause of morbidity and mortality in cirrhosis. This study aims to define the determinants of NI development and its impact on 30-day outcomes among hospitalized patients with cirrhosis. METHODS: North American Consortium for the Study of End-Stage Liver Disease enrolled patients with cirrhosis who were admitted nonelectively. Admission variables and 30-day outcomes were compared between patients with and without NI. These were also compared based on whether there was an isolated admission infection, NI, or both. Models were created for NI development using admission variables and for 30-day mortality. RESULTS: The study included 2,864 patients; of which, 15% (n = 436) developed NI. When comparing NI vs no NI, 1,866 patients were found to be infection free, whereas 562 had admission infections only, 228 had only NI, and 208 had both infections. At admission, patients with NI were more likely to be infected and have advanced cirrhosis. NIs were associated with higher rates of acute-on-chronic liver failure, death, and transplant regardless of admission infections. Patients with NI had higher respiratory infection, urinary tract infection, Clostridium difficile infection, fungal infections, and infection with vancomycin-resistant enterococci compared with patients without NI. Risk factors for NIs were admission infections, model for end-stage liver disease (MELD) > 20, systemic inflammatory response syndrome criteria, proton pump inhibitor, rifaximin, and lactulose use, but the regression model (sensitivity, 0.67; specificity, 0.63) was not robust. Age, alcohol etiology, admission MELD score, lactulose use, acute-on-chronic liver failure, acute kidney injury, intensive care unit, and NI increased the risk of death, whereas rifaximin decreased the risk of death. DISCUSSION: NIs are prevalent in hospitalized patients with cirrhosis and are associated with poor outcomes. Although higher MELD scores and systemic inflammatory response syndrome are associated with NI, all hospitalized patients with cirrhosis require vigilance and preventive strategies.