Citations

Background Endovascular treatment with the woven endobridge (WEB) device has been widely utilized for managing intracranial aneurysms. However, predicting the probability of achieving adequate occlusion (Raymond–Roy classification 1 or 2) remains challenging. Objective Our study sought to develop and validate a predictive calculator for adequate occlusion using the WEB device via data from a large multi-institutional retrospective cohort. Methods We used data from the WorldWide WEB Consortium, encompassing 356 patients from 30 centers across North America, South America, and Europe. Bivariate and multivariate regression analyses were performed on a variety of demographic and clinical factors, from which predictive factors were selected. Calibration and validation were conducted, with variance inflation factor (VIF) parameters checked for collinearity. Results A total of 356 patients were included: 124 (34.8%) were male, 108 (30.3%) were elderly (≥65 years), and 118 (33.1%) were current smokers. Mean maximum aneurysm diameter was 7.09 mm (SD 2.71), with 112 (31.5%) having a daughter sac. In the multivariate regression, increasing aneurysm neck size (OR 0.706 [95% CI: 0.535–0.929], p = 0.13) and partial aneurysm thrombosis (OR 0.135 [95% CI: 0.024–0.681], p = 0.016) were found to be the only statistically significant variables associated with poorer likelihood of achieving occlusion. The predictive calculator shows a c-statistic of 0.744. Hosmer–Lemeshow goodness-of-fit test indicated a satisfactory model fit with a p-value of 0.431. The calculator is available at: https://neurodx.shinyapps.io/WEBDEVICE/ . Conclusion The predictive calculator offers a substantial contribution to the clinical toolkit for estimating the likelihood of adequate intracranial aneurysm occlusion by WEB device embolization.

The Program for the Education and Enrichment of Relational Skills (PEERS®) is an evidence-based intervention developed for autistic individuals to support social communication, peer interactions, independence, and interpersonal relationships. Despite a demonstrated effectiveness for young autistic individuals in the US and several other countries, PEERS has yet to be modified to support the needs of autistic adults across the lifespan. The present study describes how our team sought autistic voices to adapt PEERS for adults of any age. Specifically, we aimed to address the needs of middle-aged and older adults and adapt the curriculum to be more neurodiversity-affirming. Between two cohorts that completed the program consecutively, we evaluated the acceptability of the adapted PEERS program and made refinements based on feedback from autistic participants and their study partners. Results indicated that Cohort 2 reported higher satisfaction with the PEERS components and overall program than Cohort 1, suggesting effective refinement. We present a framework of adaptations that more specifically address the needs of middle-aged and older adults in a neurodiverse-affirming way compared to previous iterations. Our approach to implementing an adapted PEERS curriculum across the adult lifespan may serve as a model for improved clinical care and cultivate the acceptance of neurodiversity in the interpersonal domains of autistic adults’ lives.

Background: Hospitalization represents a major access point for prescription opioids, yet little is known regarding patterns and outcomes of opioid exposures before and after hospitalization for critical illness. Methods: This is an observational, population-based cohort study of adults (≥18 years) hospitalized for critical illness from 2010 to 2019. Multivariable models assess associations between opioid exposures prior to hospitalization, classified according to the Consortium to Study Opioid Risks and Trends, and posthospitalization opioid exposures and clinical outcomes through 1-year posthospitalization. Results: Of 11 496 patients, 6318 (55%) were men with a median age of 66 (51, 79) years and 40% (n = 4623) surgical admissions. Prehospitalization opioid availability included 8449 (73%) none, 2117 (18%) short-term, 471 (4%) episodic, and 459 (4%) long-term. Thirty-nine percent (4144/10 708) of hospital survivors were discharged with opioids, with higher prescribing rates for surgical admissions (55%). Greater preadmission opioid exposures were associated with higher prevalent opioid availability at 1 year (odds ratio [95% confidence interval] 24.1 [18.3-31.8], 9.42 [7.18-12.3], and 2.55 [2.08-3.12] for long-term, episodic, and short-term exposures, respectively, vs none, P < .001). Greater preadmission opioid exposures were associated with longer hospitalizations (1.13 [1.04-1.23], 1.15 [1.06-1.25], and 1.08 [1.04-1.13] multiplicative increase in geometric mean, P < .001), more readmissions (hazard ratio [HR] 2.08 [1.74-2.49], 1.88 [1.56-2.26], and 1.48 [1.33-1.64], P < .001), and higher 1-year mortality (HR 1.59 [1.28-1.98], 1.75 [1.41-2.18], and 1.49 [1.32-1.69], P < .001). Similar associations were observed across surgical and nonsurgical admissions. Conclusions: Prehospitalization opioid exposures in survivors of critical illness are associated with clinical outcomes through 1 year and may serve as important prognostic markers.

AbstractPregnancy is a conjectured risk factor for pyoderma gangrenosum (PG), an autoinflammatory neutrophilic dermatosis characterized by painful ulcers. Even so, there are no available treatment guidelines for those with PG who are pregnant or breastfeeding. To describe existing treatment options, we systematically reviewed the literature on PG treatment in pregnant or breastfeeding patients. A search over four databases was completed in October 2022. Independent reviewers accomplished screening and data extraction. 18 articles met the inclusion criteria. 15 cases involved the treatment of PG during pregnancy, and three cases involved the treatment of PG while breastfeeding. Most patients did not have a history of PG prior to pregnancy (77.7%), and most did not have PG‐associated comorbidity (61.1%). Of the cases involving treatment of PG during pregnancy, the majority (73%) found treatment success with a systemic corticosteroid (SCS). Only three cases reported an adverse outcome, including premature rupture of membranes and premature birth (16.7%); all these cases involved treatment with a SCS at >0.5 mg/kg/day during pregnancy. We present a treatment algorithm for pregnant or breastfeeding patients with PG. Our findings suggest prioritizing topicals and TNF inhibitors due to more favorable side effect profiles. However, there is a paucity of data on the safety of PG therapies in pregnancy and breastfeeding, and thus, controlled studies and pregnancy registries must be pursued.

Abstract Natural prokaryotic gene repression systems often exploit DNA looping to increase the local concentration of gene repressor proteins at a regulated promoter via contributions from repressor proteins bound at distant sites. Using principles from the Escherichia coli lac operon we design analogous repression systems based on target sequence-programmable Transcription Activator-Like Effector dimer (TALED) proteins. Such engineered switches may be valuable for synthetic biology and therapeutic applications. Previous TALEDs with inducible non-covalent dimerization showed detectable, but limited, DNA loop-based repression due to the repressor protein dimerization equilibrium. Here, we show robust DNA loop-dependent bacterial promoter repression by covalent TALEDs and verify that DNA looping dramatically enhances promoter repression in E. coli. We characterize repression using a thermodynamic model that quantitates this favorable contribution of DNA looping. This analysis unequivocally and quantitatively demonstrates that optimized TALED proteins can drive loop-dependent promoter repression in E. coli comparable to the natural LacI repressor system. This work elucidates key design principles that set the stage for wide application of TALED-dependent DNA loop-based repression of target genes.

Background: Acute ischemic stroke (AIS) from primary medium vessel occlusions (MeVO) is a prevalent condition associated with substantial morbidity and mortality. Despite the common use of mechanical thrombectomy (MT) in AIS, predictors of poor outcomes in MeVO remain poorly characterized. Methods: In this prospectively collected, retrospectively reviewed, multicenter, multinational study, data from the MAD-MT (Multicenter Analysis of primary Distal medium vessel occlusions: effect of Mechanical Thrombectomy) registry were analyzed. The study included 1568 patients from 37 academic centers across North America, Asia, and Europe, treated with MT, with or without intravenous tissue plasminogen activator (IVtPA), between September 2017 and July 2021. Results: Among the 1568 patients, 347 (22.2%) experienced very poor outcomes (modified Rankin score (mRS), 5–6). Key predictors of poor outcomes were advanced age (odds ratio (OR): 1.03; 95% confidence interval (CI): 1.02 to 1.04; p < 0.001), higher baseline National Institutes of Health Stroke Scale (NIHSS) scores (OR: 1.07; 95% CI: 1.05 to 1.10; p < 0.001), pre-operative glucose levels (OR: 1.01; 95% CI: 1.00 to 1.02; p < 0.001), and a baseline mRS of 4 (OR: 2.69; 95% CI: 1.25 to 5.82; p = 0.011). The multivariable model demonstrated good predictive accuracy with an area under the receiver-operating characteristic (ROC) curve of 0.76. Conclusions: This study demonstrates that advanced age, higher NIHSS scores, elevated pre-stroke mRS, and pre-operative glucose levels significantly predict very poor outcomes in AIS-MeVO patients who received MT. These findings highlight the importance of a comprehensive risk assessment in primary MeVO patients for personalized treatment strategies. However, they also suggest a need for cautious patient selection for endovascular thrombectomy. Further prospective studies are needed to confirm these findings and explore targeted therapeutic interventions.

The NCCN Guidelines for Cutaneous Melanoma (termed Melanoma: Cutaneous ) provide multidisciplinary recommendations for diagnostic workup, staging, and treatment of patients. These NCCN Guidelines Insights focus on the update to neoadjuvant systemic therapy options and summarize the new clinical data evaluated by the NCCN panel for the recommended therapies in Version 2.2024 of the NCCN Guidelines for Cutaneous Melanoma.

Strategic projects in large healthcare organisations are often highly complex and dynamic, and they require a team of skilled business professionals to execute them. Examples of difficult, costly and extended project executions have been shared in the literature. Successful project execution involves many critical facets. One facet that continues to be of marked interest is effective resourcing of strategic projects. This paper focuses on describing a staffing approach used at Mayo Clinic (Rochester, Minnesota) to facilitate successful, agile and sustainable execution, with desired outcomes. In 2016, Management Engineering & Consulting (ME&C) began exploring a collaborative staffing model that partnered management engineers with project managers (PMs) to drive strategic, multisite projects. This ongoing collaboration model was evaluated from multiple perspectives, including project outcomes, timeliness, client and staff satisfaction and opportunities for innovation. Data and feedback on the model were collected with historical reports, surveys and focus groups with stakeholders, leaders, PMs and management engineers. The feedback and data indicated that the collaborative staffing strategy and model have further optimised service delivery, enabled professional staff to work at the highest level of their competency and dynamically blended knowledge, expertise and skills to achieve better and more sustainable overall project outcomes.

In 2018, Mayo Clinic completed the largest transformational project in its 150-year history. Mayo Clinic was prepared to take on the implementation of new software systems (Epic Systems Corp) as an integrated electronic health record (EHR) and revenue cycle management (RCM) system across all sites of the enterprise. Three foundational teams were launched for this project: leadership, project management and change management. In a project such as this, a common pitfall is to focus completely on the system and lose sight of the end users. For Mayo Clinic, the people side of change was at the forefront of the project. A robust change management team was budgeted, staffed and engaged with an experienced outside consulting partner. A goal for the change management team centred on the best way to measure the change management impact and the degree to which it was making a positive contribution in driving successful adoption of the new EHR and RCM system. With literature lacking in this area, the team moved forward with courage and quickly learned that the easy part was the development of a survey with questions mapped to the six components of the change management strategy and the phases of the awareness, desire, knowledge, ability, reinforcement (ADKAR) Model (Prosci Inc). The hard part was building the infrastructure to visually display millions of rows of data that needed to be positioned, filtered and analysed for all affected locations. The authors share the methods to measure change and explain the importance of developing a comprehensive and robust means of gathering and displaying large volumes of change management data at the project onset. This paper prepares the reader to confidently develop an organisational framework to measure and report the effectiveness of a change management strategy.