Citations

Abstract Introduction The Accreditation Council for Graduate Medical Education (ACGME) approved the first pain medicine fellowship programs over three decades ago, designed around a pharmacological philosophy. Following that, there has been a rise in the transition of pain medicine education toward a multidisciplinary interventional model based on a tremendous surge of contemporaneous literature in these areas. This trend has created variability in clinical experience and education amongst accredited pain medicine programs with minimal literature evaluating the differences and commonalities in education and experience of different pain medicine fellowships through Program Director (PD) experiences. This study aims to gather insight from pain medicine fellowship program directors across the country to assess clinical and interventional training, providing valuable perspectives on the future of pain medicine education. Methods This study involved 56 PDs of ACGME‐accredited pain fellowship programs in the United States. The recruitment process included three phases: advanced notification, invitation, and follow‐up to maximize response rate. Participants completed a standard online questionnaire, covering various topics such as subcategory fields, online platforms for supplemental education, clinical experience, postgraduate practice success, and training adequacy. Results Surveys were completed by 39/56 (69%) standing members of the Association of Pain Program Directors (APPD). All PDs allowed fellows to participate in industry‐related and professional society‐related procedural workshops, with 59% encouraging these workshops. PDs emphasized the importance of integrity, professionalism, and diligence for long‐term success. Fifty‐four percent of PDs expressed the need for extension of fellowship training to avoid supplemental education by industry or pain/spine societies. Conclusion This study highlights the challenge of providing adequate training in all Pain Medicine subtopics within a 12‐month pain medicine fellowship. PDs suggest the need for additional training for fellows and discuss the importance of curriculum standardization.

Background: International guidelines recommend targeted screening to identify gestational thyroid dysfunction. However, currently used risk factors have questionable discriminative ability. We quantified the risk for thyroid function test abnormalities for a subset of risk factors currently used in international guidelines. Methods: We included prospective cohort studies with data on gestational maternal thyroid function and potential risk factors (maternal age, body mass index [BMI], parity, smoking status, pregnancy through in vitro fertilization, twin pregnancy, gestational age, maternal education, and thyroid peroxidase antibody [TPOAb] or thyroglobulin antibody [TgAb] positivity). Exclusion criteria were pre-existing thyroid disease and use of thyroid interfering medication. We analyzed individual participant data using mixed-effects regression models. Primary outcomes were overt and subclinical hypothyroidism and a treatment indication (defined as overt hypothyroidism, subclinical hypothyroidism with thyrotropin >10 mU/L, or subclinical hypothyroidism with TPOAb positivity). Results: The study population comprised 65,559 participants in 25 cohorts. The screening rate in cohorts using risk factors currently recommended (age >30 years, parity ≥2, BMI ≥40) was 58%, with a detection rate for overt and subclinical hypothyroidism of 59%. The absolute risk for overt or subclinical hypothyroidism varied <2% over the full range of age and BMI and for any parity. Receiver operating characteristic curves, fitted using maternal age, BMI, smoking status, parity, and gestational age at blood sampling as explanatory variables, yielded areas under the curve ranging from 0.58 to 0.63 for the primary outcomes. TPOAbs/TgAbs positivity was associated with overt hypothyroidism (approximate risk for antibody negativity 0.1%, isolated TgAb positivity 2.4%, isolated TPOAb positivity 3.8%, combined antibody positivity 7.0%; p < 0.001), subclinical hypothyroidism (risk for antibody negativity 2.2%, isolated TgAb positivity 8.1%, isolated TPOAb positivity 14.2%, combined antibody positivity 20.0%; p < 0.001) and a treatment indication (risk for antibody negativity 0.2%, isolated TgAb positivity 2.2%, isolated TPOAb positivity 3.0%, and combined antibody positivity 5.1%; p < 0.001). Twin pregnancy was associated with a higher risk of overt hyperthyroidism (5.6% vs. 0.7%; p < 0.001). Conclusions: The risk factors assessed in this study had poor predictive ability for detecting thyroid function test abnormalities, questioning their clinical usability for targeted screening. As expected, TPOAb positivity (used as a benchmark) was a relevant risk factor for (subclinical) hypothyroidism. These results provide insights into different risk factors for gestational thyroid dysfunction.

Context: The quality and interprogram variability of publicly available throwing programs have not been assessed. Objective: To (1) identify publicly available interval throwing programs, (2) describe their components and structure, and (3) evaluate their quality, variability, and completeness. Data Sources: Google, Bing, Yahoo; keyword: “interval throwing program.” Study Selection: Baseball-specific publicly available programs. Study Design: Systematic review. Level of Evidence: Level 4. Data Extraction: Independent evaluation by 2 authors using a novel 21-item Quality Assessment Rubric (QAR). Results: Of the 99 included programs, 54% were designed for return from injury/surgery; 42% explicitly stated no expected timeline for completion, and approximately 40% did not provide criteria to initiate the program. Program construction was highly variable. There were broad-ranging shortest (mean: 40±8 ft, range: 20-45 ft) and longest (mean: 150±33 ft, range: 90-250 ft) long toss distances, and variable maximum numbers of mound pitches thrown before returning to game play (range: 40-120, mean: 85). Only 63% of programs provided guidelines for handling setbacks, and standardized warm-ups, arm care, and concomitant training were absent in 32%, 63%, and 47% of programs, respectively. Mean QAR completion rate and QAR item response rate were low (62 ± 4% [range, 24-91%], 62 ± 24% [range, 7-99%], respectively). Finally, only 20 (20%) programs provided at least 1 peer-reviewed reference, most of which were published >10 years ago. Conclusion: Publicly available interval throwing programs are readily available but demonstrate significant interprogram heterogeneity across multiple areas including target audience, program construction, progression, and execution. The quality and consistency of publicly available interval throwing programs is poor at this time, which may limit their utility and effectiveness for baseball players attempting to return to competition. This work identifies a multitude of deficiencies in currently available throwing programs that should be targets of future improvement efforts.

The liver transplantation (LT) evaluation and waitlisting process is subject to variations in care that can impede quality. The American Association for the Study of Liver Diseases (AASLD) Practice Metrics Committee (PMC) developed quality measures and patient-reported experience measures along the continuum of pre-LT care to reduce care variation and guide patient-centered care. Following a systematic literature review, candidate pre-LT measures were grouped into 4 phases of care: referral, evaluation and waitlisting, waitlist management, and organ acceptance. A modified Delphi panel with content expertise in hepatology, transplant surgery, psychiatry, transplant infectious disease, palliative care, and social work selected the final set. Candidate patient-reported experience measures spanned domains of cognitive health, emotional health, social well-being, and understanding the LT process. Of the 71 candidate measures, 41 were selected: 9 for referral; 20 for evaluation and waitlisting; 7 for waitlist management; and 5 for organ acceptance. A total of 14 were related to structure, 17 were process measures, and 10 were outcome measures that focused on elements not typically measured in routine care. Among the patient-reported experience measures, candidates of LT rated items from understanding the LT process domain as the most important. The proposed pre-LT measures provide a framework for quality improvement and care standardization among candidates of LT. Select measures apply to various stakeholders such as referring practitioners in the community and LT centers. Clinically meaningful measures that are distinct from those used for regulatory transplant reporting may facilitate local quality improvement initiatives to improve access and quality of care.

Abstract Exposure to repetitive head impacts in contact sports is associated with neurodegenerative disorders including chronic traumatic encephalopathy (CTE), which currently can be diagnosed only at post-mortem. American football players are at higher risk of developing CTE given their exposure to repetitive head impacts. One promising approach for diagnosing CTE in vivo is to explore known neuropathological abnormalities at post-mortem in living individuals using structural MRI. MRI brain morphometry was evaluated in 170 male former American football players ages 45–74 years (n = 114 professional; n = 56 college) and 54 same-age unexposed asymptomatic male controls (n = 54, age range 45–74). Cortical thickness and volume of regions of interest were selected based on established CTE pathology findings and were assessed using FreeSurfer. Group differences and interactions with age and exposure factors were evaluated using a generalized least squares model. A separate logistic regression and independent multinomial model were performed to predict each traumatic encephalopathy syndrome (TES) diagnosis, core clinical features and provisional level of certainty for CTE pathology using brain regions of interest. Former college and professional American football players (combined) showed significant cortical thickness and/or volume reductions compared to unexposed asymptomatic controls in the hippocampus, amygdala, entorhinal cortex, parahippocampal gyrus, insula, temporal pole and superior frontal gyrus. Post hoc analyses identified group-level differences between former professional players and unexposed asymptomatic controls in the hippocampus, amygdala, entorhinal cortex, parahippocampal gyrus, insula and superior frontal gyrus. Former college players showed significant volume reductions in the hippocampus, amygdala and superior frontal gyrus compared to the unexposed asymptomatic controls. We did not observe Age × Group interactions for brain morphometric measures. Interactions between morphometry and exposure measures were limited to a single significant positive association between the age of first exposure to organized tackle football and right insular volume. We found no significant relationship between brain morphometric measures and the TES diagnosis core clinical features and provisional level of certainty for CTE pathology outcomes. These findings suggested that MRI morphometrics detect abnormalities in individuals with a history of repetitive head impact exposure that resemble the anatomic distribution of pathological findings from post-mortem CTE studies. The lack of findings associating MRI measures with exposure metrics (except for one significant relationship) or TES diagnosis and core clinical features suggested that brain morphometry must be complemented by other types of measures to characterize individuals with repetitive head impacts.

AbstractMeningeal solitary fibrous tumors (SFT) are rare and have a high frequency of local recurrence and distant metastasis. In a cohort of 126 patients (57 female, 69 male; mean age at surgery 53.0 years) with pathologically confirmed meningeal SFTs with extended clinical follow‐up (median 9.9 years; range 15 days–43 years), we performed extensive molecular characterization including genome‐wide DNA methylation profiling (n = 80) and targeted TERT promoter mutation testing (n = 98). Associations were examined with NAB2::STAT6 fusion status (n = 101 cases; 51 = ex5‐7::ex16‐17, 26 = ex4::ex2‐3; 12 = ex2‐3::exANY/other and 12 = no fusion) and placed in the context of 2021 Central Nervous System (CNS) WHO grade. NAB2::STAT6 fusion breakpoints (fusion type) were significantly associated with metastasis‐free survival (MFS) (p = 0.03) and, on multivariate analysis, disease‐specific survival (DSS) when adjusting for CNS WHO grade (p = 0.03). DNA methylation profiling revealed three distinct clusters: Cluster 1 (n = 38), Cluster 2 (n = 22), and Cluster 3 (n = 20). Methylation clusters were significantly associated with fusion type (p < 0.001), with Cluster 2 harboring ex4::ex2‐3 fusion in 16 (of 20; 80.0%), nearly all TERT promoter mutations (7 of 8; 87.5%), and predominantly an “SFT” histologic phenotype (15 of 22; 68.2%). Clusters 1 and 3 were less distinct, both dominated by tumors having ex5‐7::ex16‐17 fusion (respectively, 25 of 33; 75.8%, and 12 of 18; 66.7%) and with variable histological phenotypes. Methylation clusters were significantly associated with MFS (p = 0.027), but not overall survival (OS). In summary, NAB2::STAT6 fusion type was significantly associated with MFS and DSS, suggesting that tumors with an ex5::ex16‐17 fusion may have inferior patient outcomes. Methylation clusters were significantly associated with fusion type, TERT promoter mutation status, histologic phenotype, and MFS.

Abstract Background: Metastatic castration-resistant prostate cancer (mCRPC) resistant to androgen receptor (AR)-targeted agents is often lethal. Unfortunately, biomarkers for this deadly disease remain under investigation, and underpinning mechanisms are ill-understood. Here, we applied epigenomic approaches to identify cell-free (cf) DNA features associated with these lethal AR-resistant mCRPC patients. Methods: Plasma from 99 mCRPC patients was collected from two independent institutions, either prior to first-line AR-targeted therapy (n = 63) or during treatment (n = 36). We applied EnhanceAR-Seq to detect alterations in the AR locus including the upstream enhancer. We then applied genome-wide cfDNA epigenomics to 43 pre-treatment plasma samples and performed both fragmentomics and methylation sequencing to delineate the biology of AR/enhancer-altered lethal mCRPC. Finally, we identified stemness genes by applying CytoTRACE to external single-cell RNA-seq data from mCRPC, and applied these to cfDNA via promoter-level methylation analysis. We then assessed these stem-associated genes in tumor bulk RNA-seq data from an independent mCRPC cohort. Results: AR/enhancer alterations were detected in 44% of pre-treatment cfDNA samples and correlated with significantly worse progression-free survival (PFS) (HR = 2.12, P = 0.01) and overall survival (OS) (HR = 2.48; P = 0.02). AR/enhancer alterations were detected in 19% of on-treatment cfDNA samples and were also associated with profoundly worse PFS (HR = 15.38, P = 0.0003) and OS (HR = 15.53, P = 0.002). Further, genome-wide cfDNA fragmentomic analysis revealed that binding sites for developmentally relevant transcription factors such as FOXA1, NKX-3 and HOXB13 were significantly more accessible in AR/enhancer-altered lethal mCRPC patients. Gene set enrichment analysis of the 20 most accessible transcription factors revealed several pathways associated with stem cell development. Interestingly, the 10 most stem-associated genes obtained using CytoTRACE applied to an external cohort of single-cell RNA-seq data from mCRPC (He et al. 2021) were promoter-hypomethylated in the plasma cfDNA of AR/enhancer-altered lethal mCRPC patients (P = 0.005). Further, metagene analysis of these stem-associated genes revealed worse PFS by Kaplan-Meier analysis (P = 0.04), which was confirmed by multivariate cox proportional hazards modeling. Our stemness metagene further stratified overall survival (P = 0.03) when applied to an external cohort of 80 mCRPC patients from Abida et al. 2019. Conclusions: Alterations in AR including the upstream enhancer are remarkably prognostic in mCRPC with pre-treatment predictive potential. The mechanism can be inferred via cfDNA epigenomic analysis and appears to involve increased tumor cell stemness in AR-altered lethal mCRPC. Citation Format: Pradeep Singh Chauhan, Irfan Alahi, Savar Sinha, Ryan Mueller, Alexander L. Shiang, Jace Webster, Ha X. Dang, Debanjan Saha, Lilli Greiner, Breanna Yang, Elisa M. Ledet, Ramandeep K. Babbra, Wenjia Feng, Peter K. Harris, Faridi Qaium, Ellen B. Jaeger, Patrick J. Miller, Sydney A. Caputo, Oliver A. Sartor, Russell K. Pachynski, Christopher A. Maher, Aadel A. Chaudhuri. Epigenomic analysis of plasma cell-free DNA identifies stemness features associated with worse prognosis in AR-altered lethal metastatic castration resistant prostate cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 983.

Background: Hip arthroscopy is rapidly advancing, with positive published outcomes at short- and midterm follow-up; however, available long-term data remain limited. Purpose: To evaluate outcomes of primary hip arthroscopy at a minimum 10-year follow-up at 2 academic centers by describing patient-reported outcomes and determining reoperation and total hip arthroplasty (THA) rates. Study Design: Case series; Level of evidence, 4. Methods: Patients with primary hip arthroscopy performed between January 1988 and April 2013 at 2 academic centers were evaluated for postoperative patient-reported outcomes—including the visual analog scale, Tegner Activity Scale score, Hip Outcome Score Activities of Daily Living and Sport Specific subscales, modified Harris Hip Score, Nonarthritic Hip Score, 12-item International Hip Outcome Tool, surgery satisfaction, and reoperations. Results: A total of 294 patients undergoing primary hip arthroscopy (age, 40 ± 14 years; 66% women; body mass index, 27 ± 6) were followed for 12 ± 3 years (range, 10-24 years) postoperatively. Labral debridement and repair were performed in 41% and 59% of patients, respectively. Of all patients who underwent interportal capsulotomy, 2% were extended to a T-capsulotomy, and 11% underwent capsular repair. At final follow-up, patients reported a mean visual analog scale at rest of 2 ± 2 and with use of 3 ± 3, a 12-item International Hip Outcome Tool of 68 ± 27, a Nonarthritic Hip Score of 81 ± 18, a modified Harris Hip Score of 79 ± 17, and a Hip Outcome Score Activities of Daily Living of 82 ± 19 and Sport Specific subscale of 74 ± 25. The mean surgical satisfaction was 8.4 ± 2.4 on a 10-point scale, with 10 representing the highest level of satisfaction. In total, 96 hips (33%) underwent reoperation—including 65 hips (22%) converting to THA. THA risk factors included older age, higher body mass index, lower lateral center-edge angle, larger alpha angle, higher preoperative Tönnis grade, as well as labral debridement and capsular nonrepair ( P≤ .039). Patients undergoing combined labral and capsular repair demonstrated a THA conversion rate of 3% compared with 31% for patients undergoing combined labral debridement and capsular nonrepair ( P = .006). Labral repair trended toward increased 10-year THA-free survival (84% vs 77%; P = .085), while capsular repair demonstrated significantly increased 10-year THA-free survival (97% vs 79%; P = .033). Conclusion: At a minimum 10-year follow-up, patients undergoing primary hip arthroscopy demonstrated high satisfaction and acceptable outcome scores. In total, 33% of patients underwent reoperation—including 22% who underwent THA. Conversion to THA was associated with patient factors including older age, higher Tönnis grade, and potentially modifiable surgical factors such as labral debridement and capsular nonrepair.