Citations

AbstractObjectiveLimited evidence guides the optimal timing of treatment after the detection of tumor growth during the observation of sporadic vestibular schwannoma (VS). The current work aimed to inform the timing of radiosurgical intervention based on an analysis of patient outcomes among those who ultimately failed stereotactic radiosurgery (SRS) and underwent salvage microsurgery.Study DesignA historical cohort study.SettingSeven centers across the United States and Norway.MethodsAdults with sporadic VS who underwent salvage microsurgery following failed primary SRS were included. The primary outcome of interest was the association between tumor size at the time of primary SRS and the ability to achieve gross total resection (GTR) and maintain postoperative House–Brackmann (HB) facial nerve grade I at the last follow‐up after salvage microsurgery.ResultsAmong 96 patients, the median (interquartile range [IQR]) cerebellopontine angle (CPA) tumor size at primary SRS was 14.5 mm (10.0‐19.0). Each 1‐mm increase in CPA tumor size at the time of primary SRS was associated with a 13% increased likelihood of near‐total/subtotal resection or most recent postoperative HB grade >I (odds ratio [OR] 1.13, 95% confidence interval [CI] 1.05‐1.21, P = .001), with an optimal tumor size threshold to distinguish this outcome of 12 mm of CPA extension (c‐index 0.73). Similarly, for each 1‐mm increase in CPA tumor size at the time of primary SRS, a 9% increase in any postoperative complication with salvage microsurgery was observed (OR 1.09, 95% CI 1.02‐1.15, P = .009).ConclusionCorroborated by size threshold surveillance data informing the timing of primary microsurgical resection, the current study suggests that VS outcomes are optimized when primary radiosurgical intervention is undertaken on growing tumors when they harbor 10–15 mm of cerebellopontine angle extension or less.

BACKGROUND: Increased specialty competitiveness, alongside the inception of virtual interviews, has increased the number of applications submitted to the Electronic Residency Application Service (ERAS) in anesthesiology. ERAS introduced signals to provide applicants with a means to demonstrate interest in a select group of residency programs. In the 2023 to 2024 application cycle, anesthesiology applicants had the opportunity to send 5 gold and 10 silver signals in a tiered system. METHODS: This multicenter, cross-sectional (exempt) research survey was created by members of the executive council of the Association of Anesthesiology Core Program Directors (AACPD) and housed and distributed through REDCap and the University of Nebraska Medical Center. Publicly available contact information of anesthesiology core program directors was obtained from the Accreditation Council for Graduate Medical Education (ACGME) website and membership roster of the AACPD. In total, 174 anesthesiology programs were identified. A survey invitation was distributed on March 12, 2024, to all programs via e-mail with reminders. The survey closed on April 30, 2024. Survey responses were collected anonymously, with instructions to provide 1 response per program. All statistical summaries and analyses were performed using SAS 9.3 (SAS Institute). RESULTS: The survey was sent to all 174 identified programs, with a response rate of 48.9%. Small programs were defined as having <44 residents, medium 44 to 62 residents, and large >62 residents. Small programs received significantly fewer applications (median 1255) than medium (1420) and large (1558) programs ( P = .0005). There was a statistically significant difference in the number of gold signals received based on program size, with large programs receiving significantly more than medium (169 vs 116, P = .0238) or small programs (168 vs 71, P < .0001). Applicants sending gold signals were more likely to receive an interview compared to those who sent silver signals (56.7% vs 31%, P ≤ .0001). Of the those interviewed, applicants who sent gold signals comprised 42% (28.7%–52.6%), whereas applicants who sent silver signals comprised 45.5% (33%–54.7%). Applicants who did not send a program signal but signaled geographically made up a smaller portion of the interview group at 3% (0%–15.4%). The percentage of matched residents sending gold signals made up 66.7% (47.1%–82.4%) of a program’s match list, whereas those sending silver signals were 25% (11.1%–33.3%) of the matched cohort. CONCLUSIONS: Anesthesiology applicants who sent program signals were selected for a large majority of available interview positions, and interviewed applicants who submitted gold and silver signals comprised the vast majority of matched resident cohorts.

AbstractBackgroundAcute lymphoblastic leukemia (ALL) in adults is aggressive, with long‐term outcomes impacted by treatment resistance and toxicity. CD52 is expressed in most cases of B‐ and T‐lineage ALL. Alemtuzumab, a humanized immunoglobulin G1 monoclonal antibody that targets CD52, was identified as a potential agent to improve treatment efficacy without increasing toxicity.MethodsIn this phase 1/2 study (Cancer and Leukemia Group B [CALGB] 10102, NCT00061945), a course of single‐agent alemtuzumab was intercalated into CALGB 19802 backbone chemotherapy after the third course of intensive chemotherapy in those who were CD52+ at diagnosis. Phase 1 tested three dose levels of subcutaneous alemtuzumab (10, 20, and 30 mg 3 times weekly for 4 weeks/12 doses) and demonstrated that 30 mg was tolerable. Phase 2 established feasibility.ResultsThe study enrolled 295 evaluable patients (115 in phase 1, 180 in phase 2); 206 (69.8%) were CD52+. Among evaluable CD52+ patients, 43.7% (90/206) completed the first three treatment modules; 97.8% (88 of 90) were treated with alemtuzumab. Alemtuzumab was associated with cytomegalovirus viremia, which occurred in 23.3% (14 of 60) of patients during and 29.2% (19 of 65) after alemtuzumab treatment. With a median follow‐up of 101.2 months, median overall survival (OS) was 26.3 months (3‐year rate, 44%; 5‐year rate, 36%; 10‐year rate, 31%). Landmark analysis at the start of the fourth course of treatment demonstrated no difference in OS or disease‐free survival between patients who did and who did not receive alemtuzumab.ConclusionAlemtuzumab was feasible to administer in adults with ALL receiving intensive chemotherapy, but was without evidence of benefit.

Background and Objectives: Physician scheduling affects job satisfaction and retention. This study explores how family medicine residency inpatient staffing relates to core faculty retention and program director (PD) perception of faculty satisfaction with work-life integration. Methods: A total of 280 family medicine residency PDs responded to the 2023 Council of Academic Family Medicine Education Research Alliance survey. We used the ꭓ2 test to explore associations among program demographics, inpatient staffing characteristics, faculty retention, and PD-reported faculty satisfaction with work-life integration. We measured associations among pairs of ordinal variables with Spearman’s correlation. Results: In two-thirds (66%) of programs, faculty cover the inpatient service at least every 8 weeks, with 40% of programs reporting averages of 70 or more hours per inpatient week; nevertheless, most programs’ faculty were perceived to be satisfied with less than 10% turnover. The number of hours per week was inversely associated with PD-reported faculty satisfaction (r=-0.21, P=.001). Faculty turnover was directly associated with community size (r=0.17, P=.01). Faculty turnover was more likely to be greater than 10% if the number of hours per inpatient week was more than 89 (odds ratio 12.4, P=.02). Faculty turnover, PD-reported faculty dissatisfaction, and plans to change inpatient staffing were all correlated (r&gt;0.28, P&lt;.0001). Conclusions: Most family medicine residencies have core faculty cover the inpatient service at least once every 8 weeks, during which they work at least 60 hours per week. Longer hours are associated with lower perceived faculty satisfaction of work-life integration, with a threshold effect on faculty turnover. Family medicine residency programs must carefully balance the needs of residents, the community served, and faculty themselves.

Achondroplasia accounts for approximately 70% of all forms of dwarfism. Cesarean delivery is often required in parturients with achondroplasia due to cephalopelvic disproportion. There is no consensus on the optimal management for cesarean delivery considering the difficulties in both general and regional anesthesia in patients with achondroplasia. The aim of this study was to explore the literature for prior case reports and series to determine the optimum anesthetic management for cesarean delivery in achondroplastic patients. We conducted a review of the literature using Embase, Medline, Scopus, and Web of Science database searches for case series and case reports on achondroplasia and pregnancy through January 2024. Conference abstracts >3 years old were excluded, as well as data on forms of dwarfism other than achondroplasia, patients taller than 147 cm, and non-English language papers. Extracted data included demographic information, anesthetic management, and reported complications. The literature review resulted in 57 manuscripts with a total of 80 anesthetics. Anesthetic management consisted of planned general anesthesia (n = 16), single injection spinal (n = 28), epidural (n = 17), combined spinal-epidural (n = 12), and intrathecal catheter (n = 1). Six patients required conversion from neuraxial anesthesia to general anesthesia due to failed neuraxial placement (n = 3), inadequate blockade (n = 2), and high neuraxial block (n = 1). Reduced dose of intrathecal bupivacaine was common in this population. Complications such as hypotension (4 in 64), inadvertent dural puncture (1 in 64), and transient paresthesia (3 in 64) during neuraxial technique were reported but were infrequent. Neuraxial anesthesia is more common and a viable option in carefully selected parturients with achondroplasia. We recommend reduction of intrathecal local anesthetic as part of a titratable neuraxial technique (ie, combined spinal-epidural) that minimizes the risk of hypotension, high spinal, and emergent intubation.

Background: Artificial intelligence (AI) stroke imaging software is becoming mainstay in many hub-and-spoke hospitals. Brainomix 360 Stroke software is the market leader in Europe focused on leveraging simple imaging (non-contrast computerized topography (NCCT) and CT angiography (CTA)) and has recently been FDA-cleared for use in the USA. We evaluated the implementation of Brainomix 360 AI Stroke software in the 17 spoke, multi-state Mayo Clinic Health System (MCHS) telestroke network. Methods: This prospective study compared decision and treatment times before and after Brainomix AI implementation, as well as clinician feedback and simulated decision making to better understand any changes seen. Patients were included if they underwent telestroke evaluation at an MCHS emergency department within 90 days of implementation (2/9/2024-8/8/2024), and excluded if they were already admitted to the hospital or if video evaluation was not performed. Data collection included demographics, clinical decisions and treatment times. Qualitative surveys were conducted at baseline and evaluation end, as well as simulated decision making in 20 de-identified cases randomized to with/without AI through an online portal. Results: A total of 907 patients were included (444 pre- and 463 post-implementation, 287 (32%) with ischemic stroke final diagnosis). Median NIHSS was 2. IVT was recommended in 20.3% (27/148 ischemic stroke patients) pre- and 25.9% (36/139) post-implementation. EVT was recommended in 16.2% (24/148) pre and 14.4% (20/139) post. AI use was associated with trends of faster telestroke activation to IVT decision (36 vs 32 mins, p=0.6), IVT administration (47 vs 40 minutes, p=0.6), and EVT decision (36 vs 33 minutes, p=0.5). In the simulation, imaging interpretation was significantly faster when randomized to AI use (3.4 vs 2.1 mins, p<0.001) and associated with improved physician confidence (62 vs 88%, p=0.004). Qualitative feedback from 14/24 neurologists showed the greatest perceived value was improved confidence of treatment decisions (43%) and faster triaging (36%). Most value was gained from e-ASPECTS (NCCT) and LVO modules. Conclusion: This service evaluation highlighted the opportunity to improve efficiency of decision making even in the setting of a well-developed telestroke system. The impact was underpinned by the improved speed and confidence of imaging interpretation reflected in an offline simulation and qualitative feedback.

Abstract Background Pharmacokinetics of beta-lactams vary widely in neonatal and pediatric patients due to developmental biology and critical illness. Cefepime (FEP), meropenem (MEM), and piperacillin/tazobactam (TZP) are highly susceptible to pharmacokinetic changes as hydrophilic, small molecules with renal clearance. Subtherapeutic levels are associated with clinical and microbiologic failure, and supratherapeutic levels associated with toxicity. Beta-lactam therapeutic drug monitoring (TDM) may optimize the effectiveness and safety of these agents. The purpose of this investigation is to describe the % of pediatric and neonatal patients with beta-lactam serum levels within target range. Methods In August 2023, TDM launched at the Mayo Clinic Children’s Center for select patients treated with FEP, MEM, or TZP with expected durations ≥ 48 hours, or who were on kidney replacement therapy (KRT), extracorporeal membrane oxygenation (ECMO), weighed &gt; 120 kg, had a BMI &gt; 95th percentile, or at the discretion of pediatric ID team. Validated drug assays were performed daily, Monday through Friday. A two-level sampling strategy was preferred with a peak 1 hour after the end of the infusion and a trough 30 minutes before the next dose. Empiric trough target ranges were set at FEP 8-50 mg/L, MEM 2-30 mg/L, and piperacillin 16-150 mg/L. These target ranges were adjusted with confirmed microbiology to a time above the minimum inhibitory concentration of the organism for 100% of the dosing interval (100%T &gt; MIC). Results From August 2023 to April 2024, 74 episodes of TDM were performed on 45 patients. Thirty-seven (82%) patients were in an intensive care unit (ICU) at the time of TDM, 8/45 (22%) of whom were in the neonatal ICU. Target range was achieved in 67% of patients on FEP, 50% on MEM, and 52% on TZP. Median (IQR) trough values were 22.1 (8.6, 44.2) mg/L for FEP, 0.6 (0, 4.1) mg/L for MEM, and 15.5 (3.8, 27.1) mg/L for TZP. Seven levels were above target for FEP and 0 for MEM and TZP. Seven levels were below target for FEP, 4 for MEM, and 11 for TZP. Conclusion Implementation of a TDM program for FEP, MEM and TZP in pediatric and neonatal patients revealed drug levels frequently outside target range. TDM may facilitate dose individualization to optimize medication efficacy and minimize toxicity. Disclosures Raymond Stetson, MD, MS, Moderna: Grant/Research Support Christina G. Rivera (O'Connor), Pharm.D, Gilead Sciences: Board Member Erin F. Barreto, PharmD, MSc, Baxter Health: Advisor/Consultant|Wolters Kluwer: Advisor/Consultant

Abstract Background With progressive understanding of the natural history of COVID-19 and accumulation of knowledge on clinical management, treatment guidelines recommended several options including remdesivir (RDV), a broad-spectrum antiviral. Given the evolving nature of COVID-19, it is critical to capture the totality of scientific evidence to inform clinical decision making. We conducted a systematic literature review (SLR) to summarize the mortality endpoint for RDV among hospitalized adults throughout COVID-19 eras and contrasted with evidence informing treatment recommendations in clinical guidelines. Methods We systematically searched MEDLINE, Embase and Cochrane Library databases for interventional and observational studies examining RDV efficacy. Clinical trial registries, Cochrane COVID-19 Study Register, and conference abstracts were hand-searched (Fig1). Case reports and case studies were excluded. A review of most recent RDV recommendations across guidelines was conducted. Results From Dec ’19 to Dec ’22, 123 relevant publications were identified. In ’23, the evidence grew significantly, with 70 new publications. In total, 193 publications were evaluated, and 122 unique studies were included. While early randomized clinical trials (RCT) and small sample size observational studies did not universally demonstrate a significant difference in mortality in all severity groups of RDV-treated patients, real-world studies with larger sample sizes showed a significant impact across disease severity levels, regardless of COVID-19 era (Table1). Guideline recommendations for COVID-19 treatment with RDV are based on early RCTs (Table2) and most have not been updated (Fig2). Conclusion Our comprehensive evaluation of scientific literature indicates that evidence of RDV impact on mortality in hospitalized COVID-19 patients continued to grow and cover full range of disease severity. Guideline recommendations have not evolved in parallel which may explain differing recommendations in certain subgroups (e.g. IMV/ECMO). To assure that providers in the hospital setting are aware of and deploy evidence-based optimal care for patients with COVID-19, recommendations should rely on current evidence, including real-world data. Disclosures Essy Mozaffari, PharmD, MPH, MBA, Gilead Sciences, Inc.: Employee|Gilead Sciences, Inc.: Stocks/Bonds (Public Company) Michele Bartoletti, MD, PhD, Advan pharma: Advisor/Consultant|Advan pharma: Honoraria|Biomereux: Honoraria|Gilead: Advisor/Consultant|Gilead: Honoraria|Infectopharma: Advisor/Consultant|Msd: Advisor/Consultant|Msd: Grant/Research Support|Msd: Honoraria|Pfizer: Honoraria Alpesh N. Amin, MD, MBA, Alexion: Advisor/Consultant|Aseptiscope: Advisor/Consultant|AstraZeneca: Advisor/Consultant|Bayer: Advisor/Consultant|Dexcom: Advisor/Consultant|Eli Lilly: Advisor/Consultant|Ferring: Advisor/Consultant|Gilead: Advisor/Consultant|GSK: Advisor/Consultant|Heartrite: Advisor/Consultant|Nova Nordisk: Advisor/Consultant|Pfizer: Advisor/Consultant|Renibus: Advisor/Consultant|Reprieve: Advisor/Consultant|Salix: Advisor/Consultant|Seres: Advisor/Consultant|Spero: Advisor/Consultant Yohei Doi, MD, PhD, bioMerieux: Lecture fees|Entasis: Grant/Research Support|Fujifilm: Advisor/Consultant|Gilead Sciences: Advisor/Consultant|GSK: Advisor/Consultant|KANTO CHEMICAL CO.,INC.: Grant/Research Support|KANTO CHEMICAL CO.,INC.: Patent for genotyping kit|MeijiSeika Pharma: Advisor/Consultant|Moderna: Advisor/Consultant|MSD: Lecture fees|Pfizer: Advisor/Consultant|Shionogi & Co., Ltd.: Grant/Research Support|Shionogi & Co., Ltd.: Lecture fees Paul LOUBET, MD, PhD, Astrazeneca: Advisor/Consultant|Gilead: Advisor/Consultant|Moderna: Advisor/Consultant|Pfizer: Advisor/Consultant Christina G. Rivera (O'Connor), Pharm.D, Gilead Sciences: Board Member Michael Roshon, MD/PhD, MD/PhD, Gilead: Honoraria Thomas F. Oppelt, PharmD, BCPS, Gilead Sciences, Inc: I am an employee of Gilead Sciences, Inc|Gilead Sciences, Inc: Stocks/Bonds (Public Company) Mel Chiang, Ph.D., Gilead Sciences: I am an employee of Gilead Sciences|Gilead Sciences: Stocks/Bonds (Public Company)