Faculty Bibliography

Postnatal maturation of the mammalian heart requires a vast increase in respiratory enzymes. The mitochondria-specific lipid cardiolipin (CL) is essential for respiratory chain integrity but has no defined function in heart maturation. Here, we determined how the two steps of CL biogenesis, de novo synthesis and acyl chain remodeling, affect the maturation of cardiac mitochondria in mice. Cardiomyocyte-restricted deletion of the CL synthase Crls1 in late gestation does not affect CL levels at birth but blocks the increase in the tissue concentration of CL observed during normal postnatal maturation. Deletion of Crls1 prevents the postnatal rise in cristae density and in the intramitochondrial concentration of respiratory proteins. This inhibits cardiac development, precipitates heart failure, and causes death by the age of 2 weeks. In contrast, ablation of CL remodeling by cardiomyocyte-restricted deletion of Tafazzin does not disrupt mitochondrial maturation or cardiac development, although it has a similar effect on the CL concentration and profoundly alters the CL species composition. Our data show that CL synthesis, but not CL remodeling, controls expression of the respiratory chain by a mechanism independent of the CL concentration.

BACKGROUND:Chronic axial spinal pain is a major contributor to disability and healthcare expenditures, with facet joints recognized as one of the established sources of pain. OBJECTIVE:To provide evidence-based guidance in performing diagnostic and therapeutic facet joint interventions. METHODS:A multidisciplinary panel of experts from various medical and pharmaceutical disciplines, convened by the American Society of Interventional Pain Physicians (ASIPP), reviewed the available evidence, considered patient perspectives, and formulated recommendations for facet joint interventions in the management of chronic pain.The methodology included the development of key questions with evidence-based statements and recommendations. Grading of the evidence and recommendations followed a modified approach described by ASIPP, the Grading of Recommendations Assessment, Development and Evaluation (GRADE) methodology, and the Agency for Healthcare Research and Quality (AHRQ) methods for grading strength of recommendations. The evidence review included existing guidelines, systematic reviews, comprehensive reviews, randomized controlled trials (RCTs), and observational studies evaluating the effectiveness and safety of facet joint interventions in chronic pain management.In the development of consensus statements and guidelines, a modified Delphi technique was utilized to minimize bias related to group interactions. Panelists without a primary conflict of interest voted on approval of specific guideline statements. Each panelist was permitted to suggest revisions to guideline wording and provide additional qualifying remarks or comments regarding implementation of the guidelines in clinical practice. To achieve consensus and inclusion in the final guidelines, each guideline statement required at least 80% agreement among eligible panel members without a primary conflict of interest. RESULTS:A total of 48 authors participated in the development of these guidelines, of whom 39 participated in the voting process. A total of 37 recommendations were developed, with 100% acceptance for all items. The Summary of Recommendations is presented separately. These recommendations addressed diagnostic, therapeutic, and special considerations related to facet joint interventions. For diagnostic and therapeutic interventions, the level of evidence ranged from II to III, with moderate to strong recommendations. For special considerations and safety assessments, the level of evidence ranged from II to V. The evidence provided recommendations regarding diagnosis, treatment, sedation, concurrent antithrombotic therapy, and precautions required in special clinical circumstances. LIMITATIONS/CONCLUSIONS:The limitations of these guidelines include a paucity of high-quality studies in some aspects of diagnosis and therapy. CONCLUSION/CONCLUSIONS:These guidelines for facet joint interventions were developed through a comprehensive review of the literature, including methodologic quality assessment and determination of the level of evidence and strength of recommendations. DISCLAIMER/CONCLUSIONS:These guidelines are based on the best available evidence and do not constitute inflexible treatment recommendations. Due to the changing body of evidence, this document is not intended to be a "standard of care."

BACKGROUND:Chronic axial spinal pain is one of the leading causes of disability. The literature demonstrates that expenditures for low back and neck pain continue to rise, not only in parallel with increasing disability, but also with escalating healthcare costs, accounting for the highest spending among multiple disease categories. Based on current evidence utilizing controlled diagnostic blocks, facet joints, nerve root dura, and sacroiliac joints have been identified as potential sources of spinal pain. STUDY DESIGN/METHODS:A systematic review of the diagnostic accuracy of spinal facet joint nerve blocks. OBJECTIVE:To determine the diagnostic accuracy of spinal facet joint nerve blocks in chronic spinal pain. METHODS:Methodological quality of the included studies was assessed using the Quality Appraisal of Reliability Studies (QAREL) instrument. Only diagnostic accuracy studies meeting at least 50% of the predefined inclusion criteria were included in the analysis.The strength of evidence was graded using the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) criteria. Levels of evidence were classified using a modified best evidence synthesis, ranging from Level I to Level V.Data sources included relevant literature identified through PubMed and other electronic searches published from 1966 through September 2025, Cochrane reviews, and manual searches of the bibliographies of primary and review articles. OUTCOME MEASURES/METHODS:Eligible studies were required to use placebo-controlled or comparative local anesthetic blocks. A positive diagnostic standard was defined as at least 50% pain relief from baseline scores along with the ability to perform previously painful movements. RESULTS:The available evidence demonstrated Level I for lumbar facet joint nerve blocks, based on 18 studies employing dual diagnostic blocks, demonstrating 75% to 80% pain relief, with an average prevalence of 16% to 45% and estimated or presumed false-positive rates of 25% to 50%.Evidence for the diagnosis of cervical facet joint pain using cervical facet joint nerve blocks is Level II, derived from 12 controlled diagnostic accuracy studies, showing substantial heterogeneity and internal inconsistency. Reported prevalence ranged from 36% to 67% with ≥ 80% pain relief and estimated or presumed false-positive rates of 26% to 63%.The level of evidence for the diagnostic accuracy of thoracic facet joint nerve blocks is Level II, based on 3 studies using dual diagnostic blocks, demonstrating 80% or greater pain relief, with prevalence ranging from 34% to 48% and estimated or presumed false-positive rates ranging from 42% to 58%. LIMITATIONS/CONCLUSIONS:Limitations of this systematic review include the limited number of studies involving the thoracic spine, ongoing debate regarding the appropriate reference standard, challenges in determining false-positive rates, concerns regarding the appropriateness of diagnostic blocks, the scarcity of recent publications, and issues related to clinical utility. CONCLUSION/CONCLUSIONS:There is Level I evidence for the diagnostic accuracy of lumbar facet joint nerve blocks and Level II evidence for cervical and thoracic facet joint nerve blocks in the evaluation of chronic spinal pain.

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.

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.

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.