Barkun, Alan

Abstract Optimal management of anticoagulation for patients with aortic mechanical heart valves (MHVs) receiving vitamin K antagonists (VKAs) undergoing gastrointestinal endoscopic procedures is clinically challenging. Risk of bleeding from an unanticipated polypectomy or biopsy further complicates this issue. Current guidelines on use of bridging with low-molecular-weight heparin (LMWH) for these procedures are based on low-quality evidence. We conducted a subanalysis of a retrospective, multicenter observational study of adult patients with aortic MHVs receiving VKAs who underwent elective gastrointestinal endoscopies (colonoscopy or upper endoscopy). We included patients who underwent the procedure between July 1, 2020, and July 1, 2023, at five centers in Canada and the United States Patients with procedures performed on separate days within a 30-day period were excluded. Efficacy and safety outcomes included thromboembolic events, major bleeding (MB), and clinically relevant non-major bleeding (CRNMB) in the 30 days post procedure. A total of 192 endoscopic procedures were analyzed. Median (interquartile range [IQR]) patient age was 66 years (58.2–72.8) and 22% were female. Warfarin was interrupted for 185 procedures (96%). Among these, 119 (64%) received LMWH bridging: 33 (17%) pre-procedure only, 10 (5%) post-procedure only, and 76 (40%) both pre- and post-procedure. Post-procedure LMWH was initiated a median (IQR) of 1 day (1–1) and discontinued 5 days post-procedure (3–8). MB occurred in two patients (1%), CRNMB in two patients (1%), and one death (0.5%) was identified; no thromboembolic events occurred. Prior to propensity score matching (PSM), post-procedure LMWH with or without pre procedure LMWH was associated with the composite outcome of MB and CRNMB (P = 0.034), although not with MB or CRNMB individually. After stepwise regression and PSM analyses, no significant differences in bleeding outcomes were observed between patients who received LMWH bridging and those who did not. Our findings indicate that although adverse thrombotic events were rare and use of post-procedure LMWH bridging was significantly associated with a small absolute increased risk of bleeding, it was not significant after PSM. Larger prospective studies are needed to better inform antithrombotic management guidelines for patients with aortic MHVs undergoing gastrointestinal endoscopy.

Importance Tau positron emission tomography (PET) allows in vivo detection of neurofibrillary tangles, a core neuropathologic feature of Alzheimer disease (AD). Objective To provide estimates of the frequency of tau PET positivity and its associated risk of clinical outcomes. Design, Setting, and Participants Longitudinal study using data pooled from 21 cohorts, comprising a convenience sample of 6514 participants from 13 countries, collected between January 2013 and June 2024. Cognitively unimpaired individuals and patients with a clinical diagnosis of mild cognitive impairment (MCI), AD dementia, or other neurodegenerative disorders were included. Exposures Tau PET with flortaucipir F 18, amyloid-β (Aβ) PET, and clinical examinations. Tau PET scans were visually rated as positive according to a US Food and Drug Administration– and European Medicines Agency–approved method, designed to indicate the presence of advanced neurofibrillary tangle pathology (Braak stages V-VI). Main Outcomes and Measures Frequency of tau PET positivity and absolute risk of clinical progression (eg, progression to MCI or dementia). Results Among the 6514 participants (mean age, 69.5 years; 50.5% female), median follow-up time ranged from 1.5 to 4.0 years. Of 3487 cognitively unimpaired participants, 349 (9.8%) were tau PET positive; the estimated frequency of tau PET positivity was less than 1% in those aged younger than 50 years, and increased from 3% (95% CI, 2%-4%) at 60 years to 19% (95% CI, 16%-24%) at 90 years. Tau PET positivity frequency estimates increased across MCI and AD dementia clinical diagnoses (43% [95% CI, 41%-46%] and 79% [95% CI, 77%-82%] at 75 years, respectively). Most tau PET–positive individuals (92%) were also Aβ PET positive. Cognitively unimpaired participants who were positive for both Aβ PET and tau PET had a higher absolute risk of progression to MCI or dementia over the following 5 years (57% [95% CI, 45%-71%]) compared with both Aβ PET–positive/tau PET–negative (17% [95% CI, 13%-22%]) and Aβ PET–negative/tau PET–negative (6% [95% CI, 5%-8%]) individuals. Among participants with MCI at the time of the tau PET scan, an Aβ PET–positive/tau PET–positive profile was associated with a 5-year absolute risk of progression to dementia of 70% (95% CI, 59%-81%). Conclusions and Relevance In a large convenience sample, a positive tau PET scan occurred at a nonnegligible rate among cognitively unimpaired individuals, and the combination of Aβ PET positivity and tau PET positivity was associated with a high risk of clinical progression in both preclinical and symptomatic stages of AD. These findings underscore the potential of tau PET as a biomarker for staging AD pathology.

Abstract Background and study aims Use of fluoroscopy in gastrointestinal endoscopy is an essential aid in advanced endoscopic interventions. However, it also raises concerns about radiation exposure. This study aimed to develop consensus-based statements for safe and effective use of fluoroscopy in gastrointestinal endoscopy, prioritizing the safety and well-being of healthcare workers and patients. Methods A modified Delphi approach was employed to achieve consensus over three rounds of surveys. Proposed statements were generated in Round 1. In the second round, panelists rated potential statements on a 5-point scale, with consensus defined as ≥80% agreement. Statements were subsequently prioritized in Round 3, using a 1 (lowest priority) to 10 (highest priority) scale. Results Forty-six experts participated, consisting of 34 therapeutic endoscopists and 12 endoscopy nurses from six continents, with an overall 45.6% female representation (n = 21). Forty-three item statements were generated in the first round. Of these, 31 statements achieved consensus after the second round. These statements were categorized into General Considerations (n = 6), Education (n = 10), Pregnancy (n = 4), Family Planning (n = 2), Patient Safety (n = 4), and Staff Safety (n = 5). In the third round, accepted statements received mean priority scores ranging from 7.28 to 9.36, with 87.2% of statements rated as very high priority (mean score ≥ 9). Conclusions This study presents consensus-based statements for safe and effective use of fluoroscopy in gastrointestinal endoscopy, addressing the well-being of healthcare workers and patients. These consensus-based statements aim to mitigate risks associated with radiation exposure while maintaining benefits of fluoroscopy, ultimately promoting a culture of safety in healthcare settings.

INTRODUCTION: Prophylactic pancreatic stent placement (PSP) is effective for preventing pancreatitis after endoscopic retrograde cholangiopancreatography (ERCP) in high-risk cases, but the optimal technical approach to this intervention remains uncertain. METHODS: In this secondary analysis of 787 clinical trial patients who underwent successful stent placement, we studied the impact of (i) whether pancreatic wire access was achieved for the sole purpose of PSP or naturally during the conduct of the case, (ii) the amount of effort expended on PSP, (iii) stent length, (iv) stent diameter, and (v) guidewire caliber. We used logistic regression models to examine the adjusted association between each technical factor and post-ERCP pancreatitis (PEP). RESULTS: Ninety-one of the 787 patients experienced PEP. There was no clear association between PEP and whether pancreatic wire access was achieved for the sole purpose of PSP (vs occurring naturally; odds ratio [OR] 0.82, 95% confidence interval [CI] 0.37–1.84), whether substantial effort expended on stent placement (vs nonsubstantial effort; OR 1.58, 95% CI 0.73–3.45), stent length (>5 vs ≤5 cm; OR 1.01, 95% CI 0.63–1.61), stent diameter (≥5 vs <5 Fr; OR 1.13, 95% CI 0.65–1.96), or guidewire caliber (0.035 vs 0.025 in; 0.83, 95% CI 0.49–1.41). DISCUSSION: The 5 modifiable technical factors studied in this secondary analysis of large-scale randomized trial data did not appear to have a strong impact on the benefit of prophylactic PSP in preventing PEP after high-risk ERCP. Within the limitations of post hoc subgroup analysis, these findings may have important implications in procedural decision making and suggest that the benefit of PSP is robust to variations in technical approach.

INTRODUCTION: The periprocedural management of patients with atrial fibrillation (AF) using a direct oral anticoagulant (DOAC) undergoing elective gastrointestinal (GI) endoscopic procedure remains uncertain. We investigated the safety of a standardized periprocedural DOAC management strategy. METHODS: The Periprocedural Anticoagulation Use for Surgery Evaluation cohort study enrolled adult patients receiving a DOAC (apixaban, rivaroxaban, or dabigatran) for AF scheduled for an elective procedure or surgery. This analysis addresses patients undergoing digestive endoscopy. Standardized periprocedural management consisted of DOAC interruption 1 day preendoscopy with resumption 1 day after procedure at low-moderate risk of bleeding or 2 days in case of a high bleeding risk. Thirty-day outcomes included GI bleeding, thromboembolic events, and mortality. RESULTS: Of 556 patients on a DOAC (mean [SD] age of 72.5 [8.6] years; 37.4% female; mean CHADS 2 score 1.7 [1.0]), 8.6% were also on American Society of Anesthesiology (ASA) and 0.7% on clopidogrel. Most of the patients underwent colonoscopies (63.3%) or gastroscopies (14.0%), with 18.9% having both on the same procedural day. The mean total duration of DOAC interruption was 3.9 ± 1.6 days. Four patients experienced an arterial thromboembolic event (0.7%, 0.3%–1.8%) within 24.2 ± 5.9 days of DOAC interruption. GI bleeding events occurred in 2.5% (1.4%–4.2%) within 11.1 ± 8.1 days (range: 0.6; 25.5 days) of endoscopy, with major GI bleeding in 0.9% (0.4%–2.1%). Three patients died (0.5%; 0.2%–1.6%) 15.6–22.3 days after the endoscopy. DISCUSSION: After a contemporary standardized periprocedural management strategy, patients with AF undergoing DOAC therapy interruption for elective digestive endoscopy experienced low rates of arterial thromboembolism and major bleeding.

AbstractWe conducted systematic reviews of predefined clinical questions and used the Grading of Recommendations, Assessment, Development and Evaluations approach to develop recommendations for the periendoscopic management of anticoagulant and antiplatelet drugs during acute gastrointestinal (GI) bleeding and the elective endoscopic setting. The following recommendations target patients presenting with acute GI bleeding: For patients on warfarin, we suggest against giving fresh frozen plasma or vitamin K; if needed, we suggest prothrombin complex concentrate (PCC) compared with fresh frozen plasma administration; for patients on direct oral anticoagulants (DOACs), we suggest against PCC administration; if on dabigatran, we suggest against the administration of idarucizumab, and if on rivaroxaban or apixaban, we suggest against andexanet alfa administration; for patients on antiplatelet agents, we suggest against platelet transfusions; and for patients on cardiac acetylsalicylic acid (ASA) for secondary prevention, we suggest against holding it, but if the ASA has been interrupted, we suggest resumption on the day hemostasis is endoscopically confirmed. The following recommendations target patients in the elective (planned) endoscopy setting: For patients on warfarin, we suggest continuation as opposed to temporary interruption (1–7 days), but if it is held for procedures with high risk of GI bleeding, we suggest against bridging anticoagulation unless the patient has a mechanical heart valve; for patients on DOACs, we suggest temporarily interrupting rather than continuing these; for patients on dual antiplatelet therapy for secondary prevention, we suggest temporary interruption of the P2Y12 receptor inhibitor while continuing ASA; and if on cardiac ASA monotherapy for secondary prevention, we suggest against its interruption. Evidence was insufficient in the following settings to permit recommendations. With acute GI bleeding in patients on warfarin, we could not recommend for or against PCC administration when compared with placebo. In the elective periprocedural endoscopy setting, we could not recommend for or against temporary interruption of the P2Y12 receptor inhibitor for patients on a single P2Y12 inhibiting agent. We were also unable to make a recommendation regarding same-day resumption of the drug vs 1–7 days after the procedure among patients prescribed anticoagulants (warfarin or DOACs) or P2Y12 receptor inhibitor drugs because of insufficient evidence.

We conducted systematic reviews of predefined clinical questions and used the Grading of Recommendations, Assessment, Development and Evaluations approach to develop recommendations for the periendoscopic management of anticoagulant and antiplatelet drugs during acute gastrointestinal (GI) bleeding and the elective endoscopic setting. The following recommendations target patients presenting with acute GI bleeding: For patients on warfarin, we suggest against giving fresh frozen plasma or vitamin K; if needed, we suggest prothrombin complex concentrate (PCC) compared with fresh frozen plasma administration; for patients on direct oral anticoagulants (DOACs), we suggest against PCC administration; if on dabigatran, we suggest against the administration of idarucizumab, and if on rivaroxaban or apixaban, we suggest against andexanet alfa administration; for patients on antiplatelet agents, we suggest against platelet transfusions; and for patients on cardiac acetylsalicylic acid (ASA) for secondary prevention, we suggest against holding it, but if the ASA has been interrupted, we suggest resumption on the day hemostasis is endoscopically confirmed. The following recommendations target patients in the elective (planned) endoscopy setting: For patients on warfarin, we suggest continuation as opposed to temporary interruption (1–7 days), but if it is held for procedures with high risk of GI bleeding, we suggest against bridging anticoagulation unless the patient has a mechanical heart valve; for patients on DOACs, we suggest temporarily interrupting rather than continuing these; for patients on dual antiplatelet therapy for secondary prevention, we suggest temporary interruption of the P2Y 12 receptor inhibitor while continuing ASA; and if on cardiac ASA monotherapy for secondary prevention, we suggest against its interruption. Evidence was insufficient in the following settings to permit recommendations. With acute GI bleeding in patients on warfarin, we could not recommend for or against PCC administration when compared with placebo. In the elective periprocedural endoscopy setting, we could not recommend for or against temporary interruption of the P2Y 12 receptor inhibitor for patients on a single P2Y 12 inhibiting agent. We were also unable to make a recommendation regarding same-day resumption of the drug vs 1–7 days after the procedure among patients prescribed anticoagulants (warfarin or DOACs) or P2Y 12 receptor inhibitor drugs because of insufficient evidence.