Faculty Bibliography

BACKGROUND:Parkinson's disease management is often complicated by motor fluctuations and dyskinesia. Although deep brain stimulation addresses these symptoms, its use is limited by invasiveness, potential device failure, and the need for ongoing maintenance. Magnetic resonance-guided focused ultrasound (MRgFUS) provides incisionless, image-guided ablation as an alternative. However, the benefits and harms of staged, bilateral MRgFUS pallidothalamic tractotomy have not been evaluated systematically in prospective multicentre studies. METHODS:In this prospective, multicentre, single-arm study, adults with idiopathic, levodopa-responsive Parkinson's disease and motor complications (Movement Disorders Society Unified Parkinson's Disease Rating Scale [MDS-UPDRS] part IV item 4.2 or 4.4 score ≥2) were enrolled at nine investigational centres (six in the USA, two in Spain, and one in Taiwan). Participants underwent unilateral MRgFUS pallidothalamic tractotomy to the symptom-dominant side. Contralateral pallidothalamic tractotomy followed a minimum of 6 months later for participants meeting prespecified criteria. The primary efficacy endpoint was percent change from baseline to 3 months after the second procedure in the summed MDS-UPDRS part III off-medication upper and lower extremity (ULE) motor scores. Safety outcomes were incidence, severity, and persistence of treatment-related adverse events in the 12 months after each procedure. Safety and efficacy of unilateral treatment were evaluated in the unilateral intention-to-treat (ITT) and safety populations, defined as all patients receiving one or more sonications during the first procedure. The primary outcome and safety of bilateral treatment were evaluated in the bilateral modified ITT (mITT) and safety populations, which required one or more sonications during the second procedure, a baseline motor assessment, and at least one post-bilateral motor assessment. This trial is registered at ClinicalTrials.gov, NCT04728295 and is active, not recruiting. FINDINGS/RESULTS:Between July 12, 2021, and Nov 1, 2023, 54 patients received unilateral treatment and 40 proceeded to bilateral treatment (63 [67%] were male and 31 [33%] were female) and were included in the primary analysis; 36 completed 12-month follow-up after the second procedure. Median bilateral ULE motor scores decreased from 33·0 points (IQR 28·0-40·5) at baseline to 21·0 points (15·0-25·5) at month 3 post-bilateral treatment, a median within-patient change of 10·5 points (5·7-20·0), representing a 32% (18-52) improvement (p<0·0001). Benefits became apparent within 1 month of the first procedure and lasted through to 12 months after the second procedure. Treatment-related adverse events occurred in 21 (39%) of 54 patients after unilateral treatment; one (2%) had a persistent moderate adverse event at 6 months. After bilateral treatment, 22 (55%) of 40 patients had treatment-related adverse events; ten (25%) had persistent moderate or severe adverse events at 12 months, mainly affecting speech, gait, and balance. One (3%) patient developed severe persistent anarthria. INTERPRETATION/CONCLUSIONS:Unilateral MRgFUS pallidothalamic tractotomy demonstrated safety and efficacy for Parkinson's disease motor complications; however, bilateral treatment offered small motor gains while increasing persistent moderate or severe adverse events. Post-bilateral treatment complications in speech, gait, and balance are consistent with historical data for bilateral ablative procedures for movement disorders. Although unilateral MRgFUS pallidothalamic tractotomy was beneficial in our study, bilateral procedures demand rigorous patient selection and counselling regarding cumulative risks. FUNDING/BACKGROUND:Insightec.

INTRODUCTION/UNASSIGNED:Since the establishment of Pain Medicine (PM) as an ACGME-recognized subspecialty in 1992, the field has undergone significant transformation. These changes brought increasing diversity in applicants` primary specialties, and the introduction of a myriad of emerging treatment paradigms. In this study, we aimed to evaluate the expectations, experiences, and perspectives of three target groups-PM trainees, program directors (PDs), and employers-to guide the evolution of PM education. METHODS/UNASSIGNED:This study employed an integrated survey approach to comprehensively evaluate PM fellowship training. Surveys were distributed through professional societies, verified forums, and direct outreach over separate 3-month periods in 2023 for PD and trainee surveys and in 2024 for the employer survey. A total of 518 respondents across PDs, employers, and trainees completed surveys; overall response rate was indeterminable due to unknown denominators, while the PD survey response rate was 69.0%. RESULTS/UNASSIGNED:The survey findings highlighted both shared and unique perspectives among the stakeholder groups. Trainees emphasized procedural volume and diversity as critical motivators for fellowship selection. Despite this focus, 70% of trainees expressed reluctance toward extending their fellowship duration, with 50% of trainees favored private practice. PDs acknowledged variability in training quality and emphasized the importance of supplemental workshops to address procedural gaps. Vast majority of PDs supported extending the fellowship duration to mitigate reliance on industry-led supplemental education. Employers underscored significant deficiencies in graduates' preparedness for independent practice, with only 7% considering fellows adequately trained under the current model. Across all groups, there was a consensus on the need for curriculum standardization and enhanced training to align with the growing complexity of PM. CONCLUSION/UNASSIGNED:This study suggests that the one-year fellowship can be re-evaluated for adequacy in preparing physicians for independent practice, particularly in advanced procedures. Alternative training pathways offer additional exposure but vary in structure and oversight.

The extended care for deceased organ donors can be challenging for resource-constrained hospitals that do not have the staff, equipment, or expertise to manage a donor. Donor care units provide a dedicated space and team for donor management, which allows for efficient and effective care. In 2020, the transplant institute at a New York City hospital established the first hospital-based donor care unit in the city with its local organ procurement organization to help alleviate the organ crisis in the United States. Hospital-based donor care units require a trusting relationship between the organ procurement organization and donor management team to maximize every donor's gift.

UNLABELLED:<p>Introduction: Tremor-predominant Parkinson's disease (TPPD) generally responds favorably to deep brain stimulation (DBS) targeting the subthalamic nucleus (STN). However, traditional stereotactic targeting of the STN does not universally yield the anticipated intraoperative improvement, prompting exploration of additional targets to achieve optimal results prior to permanent implantation of electrodes. The posterior subthalamic area (PSA), including the caudal zona incerta (cZI), have been associated with tremor suppression and can be easily compared to the neighboring STN intraoperatively. METHODS:We retrospectively compared intraoperative and clinical outcomes in tremor-dominant PD patients who prospectively underwent dual trajectory microelectrode monitor targeting the STN and PSA/cZI. We compared the neurophysiology and tremor response of both the central (STN) and posterior (PSA) trajectories in 22 patients and analyzed outcomes in those who ultimately received traditional STN (16) or PSA/cZI lead implantation (12). RESULTS:While both groups achieved substantial overall motor improvement under chronic stimulation, intraoperative test stimulation through the posterior path produced more consistent tremor arrest compared with STN. These findings suggest that positioning the DBS lead further posteriorly to engage the PSA can augment tremor suppression in select cases of TPPD without compromising other parkinsonian symptom relief. CONCLUSION/CONCLUSIONS:Our results emphasize the value of intraoperative physiological feedback in trajectory selection in tremor-predominant patients and are consistent with emerging literature that PSA/cZI DBS is an effective and potentially superior target for management of tremor in PD. </p>.

BACKGROUND:Despite a high incidence of tracheostomy-related airway complications with potentially life-threatening implications, nonsurgical tracheostomy first-responders receive limited formal education on the management of tracheostomy emergencies. While the U.K. has developed multidisciplinary guidelines and education for tracheostomy emergencies, such programs have not been widely implemented in the United States. OBJECTIVE:We evaluated the feasibility and effectiveness of an immersive virtual reality (VR) simulation training as a potential generalizable and scalable approach to tracheostomy-related emergency training. METHODS:Over the academic year 2023-2024, critical care fellows were randomized to participate in tracheostomy emergency training either via immersive VR simulation or via small group discussion sessions facilitated by expert faculty. After each case-based educational intervention, participants were asked to manage four simulated tracheostomy-related emergencies involving common tracheostomy complications. Fellow performance was evaluated using a purpose-built task trainer. Three independent and blinded graders completed fellow scoring using a checklist assessment for which validation evidence was also collected. Fellows received pre- and post-intervention surveys to measure attitudes towards VR training. RESULTS:Nineteen out of 27 eligible fellows participated in the study, managing a total of 76 simulated tracheostomy emergencies. There were 10 fellows in the VR arm and 9 fellows in the Small Group arm. Out of a total possible 26 points on the checklist assessment, fellows in the VR group scored an average of 18.03 ± 3.39 compared to the Small Group score of 16.96 ± 4.41 (P = .558). Surveys indicated improvements in fellow confidence after the training and high levels of acceptance of the VR curriculum. CONCLUSIONS:An immersive VR educational intervention for the management of tracheostomy-related emergencies was feasible and well-received by learners. There was no significant difference in post-training checklist assessment scores between the VR and Small Group participants, suggesting non-inferiority of the VR intervention, and contributing validation evidence to our task trainer simulation assessment. FUNDING/BACKGROUND:This study was funded via the APCCMPD, CHEST, and ATS Education Research Award.

Lysosomal phospholipid degradation produces two types of metabolites, either 2-lysophospholipids with saturated fatty acids in sn-1 position or 1-lysophospholipids with unsaturated fatty acids in sn-2 position. They may either be degraded further or re-used for phospholipid synthesis. We found that LPLAT7 (LPGAT1), an acyltransferase of the endoplasmic reticulum, re-acylates specifically lysosome-derived 1-lysophospholipids that carry an unsaturated chain. The enzymatic activity of LPLAT7 was specific for stearoyl-CoA and 1-lyso-2-acyl positional isomers of unsaturated lysophospholipids. In Huh7 cells, Lplat7 knockout prevented the reacylation of 1-lysophospholipids generated by the lysosomal degradation of exogenous ²H-phosphatidylcholine. Inhibition of lysosomal phospholipid degradation reduced the abundance of 1-stearoyl-2-unsaturated PC in Huh7 cells. Lplat7 knockout blunted the loss of unsaturated lysophosphatidylcholine (LPC) in response to lysosomal inhibition, suggesting that LPLAT7 consumes unsaturated LPC formed by lysosomes. In mice, Lplat7 knockout increased the concentration of unsaturated lysophospholipids, reduced the abundance of 1-stearoyl-2-unsaturated species of phosphatidylcholine, phosphatidylethanolamine, and phosphatidylserine, and inhibited the regeneration of cellular membranes. It also triggered the accumulation of triglycerides, confirming earlier reports that unsaturated lysophospholipids induce lipid droplet formation. Thus, by re-acylating unsaturated 1-lysophospholipids, LPLAT7 shifts lipid metabolism from the biogenesis of lipid droplets to the biogenesis of membranes.