Citations

Abstract Aims We aimed to evaluate the frequency, clinical features, and prognostic implications of cardiac arrest (CA) in takotsubo syndrome (TTS). Methods and results We reviewed the records of patients with CA and known heart rhythm from the International Takotsubo Registry. The main outcomes were 60-day and 5-year mortality. In addition, predictors of mortality and predictors of CA during the acute TTS phase were assessed. Of 2098 patients, 103 patients with CA and known heart rhythm during CA were included. Compared with patients without CA, CA patients were more likely to be younger, male, and have apical TTS, atrial fibrillation (AF), neurologic comorbidities, physical triggers, and longer corrected QT-interval and lower left ventricular ejection fraction on admission. In all, 57.1% of patients with CA at admission had ventricular fibrillation/tachycardia, while 73.7% of patients with CA in the acute phase had asystole/pulseless electrical activity. Patients with CA showed higher 60-day (40.3% vs. 4.0%, P < 0.001) and 5-year mortality (68.9% vs. 16.7%, P < 0.001) than patients without CA. T-wave inversion and intracranial haemorrhage were independently associated with higher 60-day mortality after CA, whereas female gender was associated with lower 60-day mortality. In the acute phase, CA occurred less frequently in females and more frequently in patients with AF, ST-segment elevation, and higher C-reactive protein on admission. Conclusions Cardiac arrest is relatively frequent in TTS and is associated with higher short- and long-term mortality. Clinical and electrocardiographic parameters independently predicted mortality after CA.

Abstract Background Radiographic leptomeningeal disease (LMD) develops in up to 30% of patients following postoperative stereotactic radiosurgery (SRS) for brain metastases. However, the clinical relevancy of this finding and outcomes after various salvage treatments are not known. Methods Patients with brain metastases, of which 1 was resected and treated with adjunctive SRS, and who subsequently developed LMD were combined from 7 tertiary care centers. LMD pattern was categorized as nodular (nLMD) or classical (“sugarcoating,” cLMD). Results The study cohort was 147 patients. Most patients (60%) were symptomatic at LMD presentation, with cLMD more likely to be symptomatic than nLMD (71% vs. 51%, P = 0.01). Salvage therapy was whole brain radiotherapy (WBRT) alone (47%), SRS (27%), craniospinal radiotherapy (RT) (10%), and other (16%), with 58% receiving a WBRT-containing regimen. WBRT was associated with lower second LMD recurrence compared with focal RT (40% vs 68%, P = 0.02). Patients with nLMD had longer median overall survival (OS) than those with cLMD (8.2 vs 3.3 mo, P < 0.001). On multivariable analysis for OS, pattern of initial LMD (nodular vs classical) was significant, but type of salvage RT (WBRT vs focal) was not. Conclusions Nodular LMD is a distinct pattern of LMD associated with postoperative SRS that is less likely to be symptomatic and has better OS outcomes than classical “sugarcoating” LMD. Although focal RT demonstrated increased second LMD recurrence compared with WBRT, there was no associated OS detriment. Focal cranial RT for nLMD recurrence after surgery and SRS for brain metastases may be a reasonable alternative to WBRT.

EXECUTIVE SUMMARY We recommend that ultrasound guidance should be used for paracentesis to reduce the risk of serious complications, the most common being bleeding. We recommend that ultrasound guidance should be used to avoid attempting paracentesis in patients with an insufficient volume of intraperitoneal free fluid to drain. We recommend that ultrasound guidance should be used with paracentesis to improve the success rates of the overall procedure. We recommend that ultrasound should be used to assess the volume and location of intraperitoneal free fluid to guide clinical decision making of where paracentesis can be safely performed. We recommend that ultrasound should be used to identify a needle insertion site based on size of the fluid collection, thickness of the abdominal wall, and proximity to abdominal organs. We recommend that the needle insertion site should be evaluated using color flow Doppler ultrasound to identify and avoid abdominal wall blood vessels along the anticipated needle trajectory. We recommend that a needle insertion site should be evaluated in multiple planes to ensure clearance from underlying abdominal organs and detect any abdominal wall blood vessels along the anticipated needle trajectory. We recommend that a needle insertion site should be marked with ultrasound immediately before performing the procedure, and the patient should remain in the same position between marking the site and performing the procedure. We recommend that using real‐time ultrasound guidance for paracentesis should be considered when the fluid collection is small or difficult to access. We recommend that dedicated training sessions, including didactics, supervised practice on patients, and simulation‐based practice, should be used to teach novices how to perform ultrasound‐guided paracentesis. We recommend that simulation‐based practice should be used, when available, to facilitate acquisition of the required knowledge and skills to perform ultrasound‐ guided paracentesis. We recommend that competence in performing ultrasound‐guided paracentesis should be demonstrated prior to independently performing the procedure on patients.

Many hospitalists incorporate point‐of‐care ultrasound (POCUS) into their daily practice to answer specific diagnostic questions or to guide performance of invasive bedside procedures. However, standards for hospitalists in POCUS training and assessment are not yet established. Most internal medicine residency training programs, the major pipeline for incoming hospitalists, have only recently begun to incorporate POCUS in their curricula. The purpose of this document is to inform a broad audience on what POCUS is and how hospitalists are using it. This document is intended to provide guidance for the hospitalists who use POCUS and administrators who oversee its use. We discuss POCUS 1) applications, 2) training, 3) assessments, and 4) program management. Practicing hospitalists must continue to collaborate with their local credentialing bodies to outline requirements for POCUS use. Hospitalists should be integrally involved in decision‐making processes surrounding POCUS program management.

Background and Purpose— Mechanical thrombectomy has been shown to improve clinical outcomes in patients with acute ischemic stroke. However, the impact of balloon guide catheter (BGC) use is not well established. Methods— STRATIS (Systematic Evaluation of Patients Treated With Neurothrombectomy Devices for Acute Ischemic Stroke) was a prospective, multicenter study of patients with large vessel occlusion treated with the Solitaire stent retriever as first-line therapy. In this study, an independent core laboratory, blinded to the clinical outcomes, reviewed all procedures and angiographic data to classify procedural technique, target clot location, recanalization after each pass, and determine the number of stent retriever passes. The primary clinical end point was functional independence (modified Rankin Scale, 0–2) at 3 months as determined on-site, and the angiographic end point was first-pass effect (FPE) success rate from a single device attempt (modified Thrombolysis in Cerebral Infarction, ≥2c) as determined by a core laboratory. Achieving modified FPE (modified Thrombolysis in Cerebral Infarction, ≥2b) was also assessed. Comparisons of clinical outcomes were made between groups and adjusted for baseline and procedural characteristics. All participating centers received institutional review board approval from their respective institutions. Results— Adjunctive technique groups included BGC (n=445), distal access catheter (n=238), and conventional guide catheter (n=62). The BGC group had a higher rate of FPE following first pass (212/443 [48%]) versus conventional guide catheter (16/62 [26%]; P =0.001) and distal access catheter (83/235 [35%]; P =0.002). Similarly, the BGC group had a higher rate of modified FPE (294/443 [66%]) versus conventional guide catheter (26/62 [42%]; P <0.001) and distal access catheter (129/234 [55%]; P =0.003). The BGC group achieved the highest rate of functional independence (253/415 [61%]) versus conventional guide catheter (23/55 [42%]; P =0.007) and distal access catheter (113/218 [52%]; P =0.027). Final revascularization and mortality rates did not differ across the groups. Conclusions— BGC use was an independent predictor of FPE, modified FPE, and functional independence, suggesting that its routine use may improve the rates of early revascularization success and good clinical outcomes. Clinical Trial Registration— URL: https://www.clinicaltrials.gov . Unique identifier: NCT02239640.

Ex vivo CRISPR/Cas9‐mediated gene editing in hepatocytes using homology‐directed repair (HDR) is a potential alternative curative therapy to organ transplantation for metabolic liver disease. However, a major limitation of this approach in quiescent adult primary hepatocytes is that nonhomologous end‐joining is the predominant DNA repair pathway for double‐strand breaks (DSBs). This study explored the hypothesis that ex vivo hepatocyte culture could reprogram hepatocytes to favor HDR after CRISPR/Cas9‐mediated DNA DSBs. Quantitative PCR (qPCR), RNA sequencing, and flow cytometry demonstrated that within 24 hours, primary mouse hepatocytes in ex vivo monolayer culture decreased metabolic functions and increased expression of genes related to mitosis progression and HDR. Despite the down‐regulation of hepatocyte function genes, hepatocytes cultured for up to 72 hours could robustly engraft in vivo. To assess functionality long‐term, primary hepatocytes from a mouse model of hereditary tyrosinemia type 1 bearing a single‐point mutation were transduced ex vivo with two adeno‐associated viral vectors to deliver the Cas9 nuclease, target guide RNAs, and a 1.2‐kb homology template. Adeno‐associated viral Cas9 induced robust cutting at the target locus, and, after delivery of the repair template, precise correction of the point mutation occurred by HDR. Edited hepatocytes were transplanted into recipient fumarylacetoacetate hydrolase knockout mice, resulting in engraftment, robust proliferation, and prevention of liver failure. Weight gain and biochemical assessment revealed normalization of metabolic function. Conclusion: The results of this study demonstrate the potential therapeutic effect of ex vivo hepatocyte‐directed gene editing after reprogramming to cure metabolic disease in a preclinical model of hereditary tyrosinemia type 1.