Faculty Bibliography

BACKGROUND AND OBJECTIVES/OBJECTIVE:Since the introduction of the Leksell Gamma Knife to North America in 1987, stereotactic radiosurgery (SRS) has increasingly been used for patients with intracranial meningiomas. We evaluated the evolving application and outcomes of meningioma patients managed with both primary and adjuvant SRS during a 35-year interval. METHODS:The authors reviewed the outcomes of meningioma patients (1229 female, 69.8%; 2220 tumors) who underwent single-fraction SRS from August 1987 to March 2022 and who had a minimum of 6-month follow-up. The rates of treated tumor control and overall survival up to 20 years after SRS were measured. Risk factors analyzed included age, sex, tumor volume, margin dose, Ki-67, anatomical location, and pre-SRS surgical resection. RESULTS:Primary SRS showed superior tumor control compared with adjuvant SRS after previous resection. Overall, 191 of 2220 patients (8.6%) had local progression at last follow-up with the 5-year, 10-year, 15-year, and 20-year tumor control rates were 92.1%, 88.3%, 84.1%, and 81.1%, respectively. The median overall survival after SRS was 17.4 years, and 2.6% of patients died related to meningioma progression. Patients treated so that ≥60% of the tumor received at least 16 Gy demonstrated significantly superior tumor control. Fifty-eight patients (3.3%) experienced symptomatic adverse radiation effects after SRS. CONCLUSION/CONCLUSIONS:SRS provided excellent local tumor control rates that extended beyond 20 years. Primary SRS was an effective strategy for patients with unresected or known WHO grade I meningiomas. Adjuvant SRS was an important option to enhance tumor control and survival in patients with residual or progressive tumors after resection.

STUDY DESIGN/METHODS:Retrospective cohort study. OBJECTIVE:Due to proximity of the surgical site to important respiratory structures, patients may undergo delayed extubation after adult cervical deformity (ACD) surgery to manage postoperative airway edema/obstruction. Herein, we evaluate relevant relationships with delayed extubation. SUMMARY OF BACKGROUND DATA/BACKGROUND:Delayed extubation is an underreported perioperative occurrence, with only a few studies conducting case-by-case reviews of prolonged intubation. METHODS:Operative ACD patients with baseline (BL) were grouped based on whether they experienced delayed extubation (DE), or leaving the OR while still intubated, versus those who were extubated successfully in the OR (non-DE). Means comparison and regression analyses identified predictors of delayed extubation and associations with peri-operative complications and outcomes. RESULTS:82 patients met inclusion criteria (mean age 62.4±13.0 y, 52.4% female, Edmonton frailty score: 5.10±2.97, ACFI score: 0.30±0.16, CCI: 1.41±1.73). 14 patients left the OR intubated, and 1(1.2%) required reintubation. DE cohort demonstrated greater Edmonton frailty scores (P=0.017) and smoking histories (P=0.031). Intraoperatively, there was a significant difference EBL (P=0.021) and rate of transfusions (DE: 27.3% v non-DE: 4.8%, P=0.12). Upper instrumented vertebra (UIV) was not associated with DE, while lower LIV increased the likelihood of DE (OR 1.1, P=0.029). Post-operatively, as expected, there was a significant difference in rate of SICU admissions (DE: 90.9% v. non-DE: 49.2%, P=0.01), although no significant differences in LOS. Greater cSVA and MGS correction from baseline was associated with increased likelihood of delayed extubation (OR 1.1, CI 95% 1.05-1.17, P<.001; OR 1.14, CI 95% 1.05-1.24, P=0.003). Furthermore, delayed extubation was a significant predictor of increased VR-Physical Component Scores (P=0.013) at 6W, and DE cohort demonstrated significantly higher VR-PCS and VR-MCS Scores at 6W (P=0.01, both). CONCLUSIONS:Baseline frailty and larger radiographic correction can be associated with delayed extubation, which can impact quality of life perioperatively. Considerations like minimizing intraoperative blood loss and degree of correction could minimize delayed extubation.

BACKGROUND:Identifying early neuropathological changes in Alzheimer's disease (AD) is important for improving treatment efficacy. Among quantitative MRI measures, transverse relaxation time (T2) has been shown to reflect tissue microstructure relevant in aging and neurodegeneration; however, findings regarding T2 changes in both normal aging and AD have been inconsistent. The association between T2 and amyloid-beta (Aβ) accumulation, a hallmark of AD pathology, is also unclear, particularly in cognitively normal individuals who may be in preclinical stages of the disease. PURPOSE/OBJECTIVE:To investigate longitudinal hippocampal T2 changes in a cognitively normal cohort of older adults and their association with global Aβ accumulation. STUDY TYPE/METHODS:Retrospective, longitudinal. SUBJECTS/METHODS:56 cognitively normal adults between 55 and 90 years of age (17 males and 39 females). FIELD STRENGTH/SEQUENCE/UNASSIGNED:3 Tesla; multi-echo spin echo sequence for T2 mapping; 18F-florbetaben positron emission tomography for Aβ measurement. ASSESSMENT/RESULTS:Bilateral hippocampal T2 and volume were extracted to relate to Aβ PET measurements. To understand variations in AD risk, participants were separated into Aβ-high and Aβ-low subgroups using a predetermined threshold. STATISTICAL TESTS/METHODS:Linear mixed-effect models and general linear models were used. A p-value < 0.025 was considered significant to account for bilateral comparisons. RESULTS:Older age was associated with increased T2 in the bilateral hippocampus (left: β = 0.30, right: β = 0.25) and smaller hippocampal volume on the left (β = -0.12). In the Aβ-low subgroup, both longitudinal T2 increase rates (β = 0.65) in the left hippocampus and bilateral cross-sectional T2 (left: β = 0.64, right: β = 0.46) were positively correlated with Aβ PET, independent of hippocampal volume. DATA CONCLUSION/CONCLUSIONS:This study provided in vivo evidence linking hippocampal T2 to Aβ accumulation in cognitively normal aging individuals, suggesting that quantitative T2 may be sensitive to microstructural changes accompanying early Aβ pathology, such as neuroinflammation, demyelination, and reduced tissue integrity. EVIDENCE LEVEL/METHODS:3. TECHNICAL EFFICACY/UNASSIGNED:Stage 2.

Cytomolecular features critical for risk-stratified treatment determination in pediatric acute myeloid leukemia (AML) were expanded in Children's Oncology Group (COG) Phase III trial AAML1831 based on previous trials. It remains unknown whether the cytomolecular risk profiles are generalizable to the real-world. We addressed this knowledge gap using a nationally representative real-world cohort of 913 pediatric AML patients. Distributions of cytomolecular risk profiles and individual markers were comparable for trial-enrolled and non-enrolled patients, as well as across social drivers of trial enrollment (race/ethnicity, language, insurance, acuity). Compared to patients with only favorable cytomolecular markers (4-year OS 89.48%; 95% CI: 84.46%-92.95%), patients with both favorable and unfavorable (hazards ratio [HR] = 2.49, 95% CI : 1.18-5.23), neutral (HR = 4.33, 95% CI : 2.75-6.82), and only unfavorable (HR = 5.80, 95% CI: 3.70-9.11) markers all had increased hazards of death. Cytomolecular risk informed by trial data appears to be generalizable to the real-world setting in pediatric AML.

Patient centered outcomes can inform the delivery of value-based rehabilitation care; however, there are many barriers that impact their routine use in clinical care. Learning health systems-which focus on improving patient centered outcomes through the iterative process of data collection, knowledge generation, and practice change-are well-positioned to overcome these barriers. In September 2024, the Learning Health Systems Rehabilitation Research Network (LeaRRn) and the Center on Health Services Training and Research (CoHSTAR) hosted the Power of Patient Centered Outcomes in Rehabilitation Learning Health Systems Summit. The Summit aimed to advance the science and practice of implementing patient-centered outcomes in learning health systems. It was organized around the following five stages of the patient centered outcome lifecycle in learning health systems: 1) selecting measures, 2) capturing data, 3) accessing data, 4) analyzing data, and 5) using data. At the Summit, experts across the rehabilitation community presented current work related to each of these lifecycle stages, discussed challenges to implementing patient centered outcomes in learning health systems during break-out groups, and generated potential solutions for improving implementation of patient centered outcomes across the five stages. The purpose of this manuscript is to disseminate the central themes of the Summit, which include common challenges and potential solutions to implementing patient centered outcomes in rehabilitation learning health systems. In doing so, this manuscript aims to serve as a catalyst for future efforts to incorporate patient centered outcomes within learning health systems in rehabilitation care.

Striae distensae, or stretch marks, are common dermal scars resulting from skin overstretching. This case series documents the occurrence of severe striae in three pediatric patients with nephrotic syndrome. This report details the clinical manifestations, including widespread and edematous striae, and explores potential etiological factors such as rapid skin stretching from edema and high-dose corticosteroid use underlying this association.

OBJECTIVE:To propose a model of international meetings of minimally invasive gynecologic surgery to decrease the carbon footprint while preserving personal interactions and the financial stability of meetings and of medical societies. WHAT WE KNOW/UNASSIGNED:International medical society meetings create a substantial carbon footprint, with 95% generated by air travel. Meetings may be organized virtually or in-person with distinct benefits and drawbacks of each format. In-person meetings encourage personal interactions, sensitive discussions, and social exchanges which are important for learning and mental well-being. WHAT WE PROPOSE/UNASSIGNED:A collaborative effort of international societies to organize annual scientific meetings at one main venue per continent and regional hubs where participants, can come together in person. Presentations and session moderations will be possible from main venues and distant hubs. Carbon footprint from air travel would decrease, while the scientific contents would be improved by the collaboration between the societies. We theorize that local hubs, easier and less expensive to reach, will increase the number of participants who face economic, geopolitical, ecological and familial barriers to travel. Regional and time differences would allow each society to preserve the specific characteristics and sessions of its conference. The preservation of one main venue on each continent, will enable a gradual transition, allowing medical societies and corporate sponsors to take advantage of the enlarged audience, while measuring the desired outcomes and being able to adjust their management. Hubs participants will be actively involved reducing the burden of travel, transitioning to a preference of joining the main venue only every second or third year. CONCLUSION/CONCLUSIONS:An economically sustainable approach towards low carbon footprint, scientifically improved and more accessible meetings needs to be considered.

BACKGROUND:Tenofovir alafenamide (TAF) has shown non-inferior efficacy to tenofovir disoproxil fumarate (TDF), with superior bone and renal safety. AIM/OBJECTIVE:To characterise 5-year TAF efficacy and safety in patients of East Asian ethnicity from pivotal Phase 3 studies. METHODS:Patients were randomised (2:1) to receive TAF or TDF for up to 3 years of double-blind treatment, followed by open-label TAF. Patients either continued TAF or switched from TDF to TAF at Week 96 (TDF → TAF 3 years) or Week 144 (TDF → TAF 2 years) of treatment. Efficacy endpoints (virologic, biochemical and serologic) and safety were assessed. RESULTS:Among 591 patients of East Asian ethnicity (TAF, n = 401; TDF → TAF 3 years, n = 84; TDF → TAF 2 years, n = 106), high rates of virologic control were achieved (89%, 94% and 92%, respectively) at Year 5 (missing = failure analysis). At Year 5, rates of alanine aminotransferase normalisation (85%, 90% and 78%) and hepatitis B e antigen loss (36%, 43% and 44%) were similar. Following the switch from TDF to TAF, changes in fasting lipid parameters were consistent with removal of the known lipid-lowering effect of TDF. However, changes in the total cholesterol to high-density lipoprotein ratio (marker of cardiovascular risk) were minimal and comparable in all groups by Year 5. Renal and bone parameters improved after switching. CONCLUSIONS:Through 5 years, rates of virologic suppression were high in East Asian patients treated with TAF or switched from TDF to TAF. TAF and TDF were well tolerated, with improved renal and bone safety observed in patients switching from TDF to TAF.

OBJECTIVE:Vacuoles E1 enzyme X-linked autoinflammatory somatic syndrome (VEXAS) is a recently identified rare genetic disorder associated with somatic mutations in the UBA1 gene. VEXAS presents with a combination of inflammatory and hematologic manifestations, leading to increased morbidity and mortality. METHODS:Given the variability in disease presentation and the limited number of studies to date, no clinical documents currently exist to provide guidance to health care providers about the management of VEXAS. To address this gap, we formed an international multidisciplinary panel of VEXAS experts. RESULTS:Through formalized meetings and a voting process, the group developed consensus clinical guidance considerations for the management of VEXAS. These considerations offer practical advice on several key topics: (1) clinical features of VEXAS, (2) UBA1 screening methods, (3) the diagnosis of myelodysplastic syndromes (MDSs) in patients with VEXAS, and (4) prognosis and management. The aim is to provide expert guidance on which patients to test, how to test for VEXAS, how to approach MDS in the context of VEXAS, and considerations for management. CONCLUSION/CONCLUSIONS:This work marks the first formal international consensus guidance for VEXAS and is intended to be used as a resource for clinicians seeking to understand the disease and its management.