Characteristic adverse events with intra-aortic balloon pumps: An analysis of the U.S. Food and Drug Administration MAUDE database from 2016 to 2021.

INTRODUCTION: The United States Food and Drug Administration Manufacturer and User Facility Device Experience (MAUDE) dataset represents a unique source for post-market surveillance data on adverse events (AE). An analysis of AE with percutaneous mechanical circulatory support (pMCS) devices has previously been reported specifically for microaxial flow pumps. The characteristic AE for the intra-aortic balloon pump (IABP) have not been similarly analyzed or reported. MATERIAL AND METHODS: All events in the MAUDE dataset between January 1, 2016 and December 31, 2021 were reviewed involving the Linear, Mega and Sensation devices (Datascope/Getinge, Wayne New Jersey). Data was analyzed by two authors and categorized based on AE type, date, event type and device-related or patient-related AE. RESULTS: A total of 2795 AE were reported over five years. Device malfunction (91.4 %) was the most frequent classification followed by death (5.6 %) and injury (3.0 %). Catheter deformation/fracture/leak accounted for 37.9 % of total AEs. The most common patient event categorization was asymptomatic (90.8 %). Vessel damage/hemorrhage occurred in 1.4 % of reports. Death occurred in 5.6 % of reports and was associated with cardiac arrest in 110 of 156 events. Thrombus formation was described in 1.1 % of AEs. Device optic AE were common and unique to Sensation catheters. Calibration errors were also more common with Sensation (4.6 % versus 1.3 %) compared to other models. CONCLUSIONS: Publicly reported AE with IABPs are predominantly device malfunctions without clinical sequelae. Injury, vascular damage, bleeding and thrombosis AEs are not frequent amongst reported AEs. Emphasis should be placed on understanding mechanisms of device malfunction in order to improve both reliability and user experience.

Bleeding risk by intensity of anticoagulation in critically ill patients with COVID-19: A retrospective cohort study.

BACKGROUND: Studies report hypercoagulability in coronavirus disease 2019 (COVID-19), leading many institutions to escalate anticoagulation intensity for thrombosis prophylaxis. OBJECTIVE: To determine the bleeding risk with various intensities of anticoagulation in critically ill patients with COVID-19 compared with other respiratory viral illnesses (ORVI). PATIENTS/METHODS: This retrospective cohort study compared the incidence of major bleeding in patients admitted to an intensive care unit (ICU) within a single health system with COVID-19 versus ORVI. In the COVID-19 cohort, we assessed the effect of anticoagulation intensity received on ICU admission on bleeding risk. We performed a secondary analysis with anticoagulation intensity as a time-varying covariate to reflect dose changes after ICU admission. RESULTS: Four hundred and forty-three and 387 patients were included in the COVID-19 and ORVI cohorts, respectively. The hazard ratio of major bleeding for the COVID-19 cohort relative to the ORVI cohort was 1.26 (95% confidence interval [CI]: 0.86-1.86). In COVID-19 patients, an inverse-probability treatment weighted model found therapeutic-intensity anticoagulation on ICU admission had an adjusted hazard ratio of bleeding of 1.55 (95% CI: 0.88-2.73) compared with standard prophylactic-intensity anticoagulation. However, when anticoagulation was assessed as a time-varying covariate and adjusted for other risk factors for bleeding, the adjusted hazard ratio for bleeding on therapeutic-intensity anticoagulation compared with standard thromboprophylaxis was 2.59 (95% CI: 1.20-5.57). CONCLUSIONS: Critically ill patients with COVID-19 had a similar bleeding risk as ORVI patients. When accounting for changes in anticoagulation that occurred in COVID-19 patients, therapeutic-intensity anticoagulation was associated with a greater risk of major bleeding compared with standard thromboprophylaxis.

The molecular tweezer CLR01 improves behavioral deficits and reduces tau pathology in P301S-tau transgenic mice.

BACKGROUND: Molecular tweezers (MTs) are broad-spectrum inhibitors of abnormal protein aggregation. A lead MT, called CLR01, has been demonstrated to inhibit the aggregation and toxicity of multiple amyloidogenic proteins in vitro and in vivo. Previously, we evaluated the effect of CLR01 in the 3 × Tg mouse model of Alzheimer's disease, which overexpresses mutant human presenilin 1, amyloid ß-protein precursor, and tau and found that subcutaneous administration of the compound for 1 month led to a robust reduction of amyloid plaques, neurofibrillary tangles, and microgliosis. CLR01 also has been demonstrated to inhibit tau aggregation in vitro and tau seeding in cell culture, yet because in Alzheimer's disease (AD) and in the 3 × Tg model, tau hyperphosphorylation and aggregation are thought to be downstream of Aß insults, the study in this model left open the question whether CLR01 affected tau in vivo directly or indirectly. METHODS: To determine if CLR01 could ameliorate tau pathology directly in vivo, we tested the compound similarly using the P301S-tau (line PS19) mouse model. Mice were administered 0.3 or 1.0 mg/kg per day CLR01 and tested for muscle strength and behavioral deficits, including anxiety- and disinhibition-like behavior. Their brains then were analyzed by immunohistochemical and biochemical assays for pathological forms of tau, neurodegeneration, and glial pathology. RESULTS: CLR01 treatment ameliorated muscle-strength deterioration, anxiety-, and disinhibition-like behavior. Improved phenotype was associated with decreased levels of pathologic tau forms, suggesting that CLR01 exerts a direct effect on tau in vivo. Limitations of the study included a relatively short treatment period of the mice at an age in which full pathology is not yet developed. In addition, high variability in this model lowered the statistical significance of the findings of some outcome measures. CONCLUSIONS: The findings suggest that CLR01 is a particularly attractive candidate for the treatment of AD because it targets simultaneously the two major pathogenic proteins instigating and propagating the disease, amyloid ß-protein (Aß), and tau, respectively. In addition, our study suggests that CLR01 can be used for the treatment of other tauopathies in the absence of amyloid pathology.

Advances in the diagnosis of acute pulmonary embolism.

Venous thromboembolism is a common disease which remains underdiagnosed because of nonspecific presentations which can range from asymptomatic incidental imaging findings to sudden death. Symptoms can overlap with comorbid cardiopulmonary disease, and risk factors that offer clues to the clinician are not always present. The diagnostic approach can vary depending on the specific clinical presentation, but ruling in the diagnosis nearly always depends on lung imaging. Overuse of diagnostic testing is another recognized problem; a cautious, evidence-based approach is required, although physician gestalt must be acknowledged. The following review offers an approach to the diagnosis of acute pulmonary embolism based on the assessment of symptoms, signs, risk factors, laboratory findings, and imaging studies.