Citations

Abstract Objectives While guidelines exist for the diagnosis and management of pediatric celiac disease (CeD), current practices in North America are not well‐described. This study aimed to explore current practice patterns to identify gaps and direct future clinical, training and research initiatives. Methods A 23‐item survey designed by the Celiac Disease Special Interest Group was distributed electronically to its members. Questions explored four themes: (1) screening and diagnosis pre and post the coronavirus disease (COVID)‐19 pandemic, (2) treatment and monitoring, (3) family screening and transition of care, and (4) CeD focused training. Results The survey response rate was 10.8% (278/2552). Most respondents were from the United States (89.9%, n = 250) and Canada (8.6%, n = 24). While endoscopy remained the gold standard, serology‐based diagnosis was accepted by 47.5% (132/278). In response to the COVID‐19 pandemic, 37.4% of providers changed their diagnostic practice. Barriers to care included: lack of insurance coverage for dietitians, wait times, and lack of CeD focused training. During fellowship 69.1% (192/278) reported no focused CeD training. Conclusion Survey results revealed practice variation regarding the diagnosis and management of CeD in North America including a substantial proportion accepting non‐biopsy, serology‐based diagnosis, which increased during the COVID‐19 pandemic. Variations in screening, diagnosis, interval surveillance, and family screening were also identified. Dedicated CeD education in pediatric gastroenterology fellowship may be an opportunity for standardizing practice and advancing research. Future North American guidelines should take current care patterns into consideration and develop new initiatives to improve care of children with CeD.

A community of practice (CoP) is a group of people who share a concern or a passion for something they do and learn how to do it better as they interact regularly. While the field of hematology/oncology has historically prioritized clinical care and biomedical research, medical education has received increasing attention within hematology/oncology in recent years. In 2018, ASCO launched the Education Scholars Program to train hematology/oncology clinicians in the science of teaching and learning. However, the number of hematology/oncology educators nationally and internationally far exceeds the capacity of the Education Scholars Program to train them. In addition, hematology/oncology educators often lack sufficient mentorship and guidance at their own institutions to pursue their chosen career path effectively. To ensure high-quality clinical care and research for generations to come, attention must be paid to improving support for hematology/oncology educators. Therefore, supported by ASCO, we developed an international medical education (Med Ed) CoP for hematology/oncology educators with the purpose of providing them with support, community, mentorship, resources, and scholarly opportunities in medical education. In this article, we describe the development of the Med Ed CoP using a three-stage framework (Establish-Grow-Sustain) including successes, challenges, and reflections. By supporting the needs of hematology/oncology educators, the Med Ed CoP will serve as a home for all who contribute to the field of hematology/oncology.

Abstract BACKGROUND: Anti-HER2 therapies have transformed the trajectory for patients with HER2-positive (HER2+) MBC. A subset of patients with HER2+ MBC do exceptionally well and remain on maintenance anti-HER2 therapy for many years. However, current therapy is non-curative and patients are treated indefinitely. While these therapies often are well-tolerated, they may cause significant toxicities, are expensive, and typically require frequent infusion and provider visits. Case reports and retrospective series demonstrate that some patients may do well after stopping anti-HER2 treatment. We currently lack prospective data on the likelihood of clinical impact of successful treatment discontinuation, outcomes among patients who progress and restart HER2-directed therapy, and tools to predict who may safely stop therapy. In this study, we will enroll pts with an exceptional response to anti-HER2 therapy. Pts may elect to either continue or stop anti-HER2 therapy and will be followed clinically and radiographically on a protocol-specified schedule. Considering the central role of patients in choosing the study intervention arm, and the unique nature of stopping therapy as a treatment intervention, patient advocates have been deeply involved in the study design to ensure patient concerns are being heard and addressed. We will retrospectively assess minimal residual disease (MRD), measured in plasma, as a biomarker of ongoing response, in a step toward shifting the treatment paradigm for pts with HER2+ MBC. METHODS: STOP-HER2 is a prospective, non-randomized, phase II, multicenter study of either continuation (cohort 1) or cessation (cohort 2) of anti-HER2 therapy in exceptional responders with HER2+ MBC. Eligible patients must have biopsy-proven HER2+ MBC by ASCO/CAP guidelines and must have been receiving first-line anti-HER2 therapy for MBC for at least 3 years without evidence of progressive disease (PD) as determined by the treating investigator. Patients with prior brain-only PD or oligo-PD outside the brain are eligible at least 2 years after local treatment to the central nervous system (CNS) and in absence of subsequent PD. Up to fifty-two participants will be enrolled into cohort 2, and an additional thirty participants enrolled into the cohort 1, at 10 US sites within the Translational Breast Cancer Research Consortium. Co-primary endpoints are the 1-year progression-free survival (PFS) in cohorts 2 and 1, separately. Secondary endpoints include the clinical benefit rate upon re-initiation of anti-HER2 therapy for patients in cohort 2 experiencing PD after treatment discontinuation; and 3-year overall survival in both cohorts. Correlative endpoints include MRD status at baseline and the correlation between MRD dynamics and outcomes. Patient-reported outcomes will be collected and analyzed, including quality of life, illness intrusiveness, financial toxicity, anxiety, and decision regret. The study will use a two-stage design to assess the primary objective of estimating the rate of participants who are free of progression at one year after discontinuing anti-HER2 therapy. If 50% or less are free of progression at one year, stopping HER2 therapy would not be considered a viable treatment plan (null hypothesis). The study is designed to have 80% power to reject the null hypothesis at the 10% type I error rate when 68% of exceptional responders are free of progression at one year after stopping HER2 therapy. STOP-HER2 began enrollment in Q2 2023 (NCT05721248). Citation Format: Heather Parsons, Kathryn Ruddy, Stefania Morganti, Karen Smith, Victoria Attaya, Eliza Kallfelz, Michelle DeMeo, Jamie LaScala, Shirley Mertz, Teri Pollastro, Patricia Spears, Adam Brufsky, Chau Dang, Susan Dent, Ahmed Elkhanany, WIlliam Gwin, Ciara O'Sullivan, Kathy Miller, Sara Nunnery, Elaine Walsh, Anna Maria Storniolo, Sara Tolaney, Nabihah Tayob, Antonio Wolff, Eric Winer, Mothaffar Rimawi, Ian Krop, Nancy Lin. The STOP-HER2 Trial: A Phase 2 Study of Stopping Trastuzumab - Outcomes in Patients with HER2+ Metastatic Breast Cancer (TBCRC 062) [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO2-20-01.

A woman in her late 60s with severe chronic obstructive pulmonary disease (COPD) and emphysema underwent bronchoscopic lung volume reduction (BLVR) with endobronchial valves (EBV) to address hyperinflation. The initial EBV placement has led to partial lobar atelectasis of the left lower lobe and resulted in significant improvement in the patient’s symptoms and lung function. However, valve migration occurred later due to pneumothorax unrelated to valves, leading to suboptimal clinical improvement. The patient achieved delayed full lobar atelectasis 21 months after EBV placement, which led to a significant clinical improvement. The patient decided to be delisted from the lung transplant list due to the improvement. This case highlights the importance of considering delayed atelectasis as a possible outcome of EBV placement and suggests the need for further exploration of the long-term implications and associations of this procedure.

Abstract Background Numerous studies demonstrate associations between serum concentrations of 25-hydroxyvitamin D (25[OH]D) and a variety of common disorders, including musculoskeletal, metabolic, cardiovascular, malignant, autoimmune, and infectious diseases. Although a causal link between serum 25(OH)D concentrations and many disorders has not been clearly established, these associations have led to widespread supplementation with vitamin D and increased laboratory testing for 25(OH)D in the general population. The benefit-risk ratio of this increase in vitamin D use is not clear, and the optimal vitamin D intake and the role of testing for 25(OH)D for disease prevention remain uncertain. Objective To develop clinical guidelines for the use of vitamin D (cholecalciferol [vitamin D3] or ergocalciferol [vitamin D2]) to lower the risk of disease in individuals without established indications for vitamin D treatment or 25(OH)D testing. Methods A multidisciplinary panel of clinical experts, along with experts in guideline methodology and systematic literature review, identified and prioritized 14 clinically relevant questions related to the use of vitamin D and 25(OH)D testing to lower the risk of disease. The panel prioritized randomized placebo-controlled trials in general populations (without an established indication for vitamin D treatment or 25[OH]D testing), evaluating the effects of empiric vitamin D administration throughout the lifespan, as well as in select conditions (pregnancy and prediabetes). The panel defined “empiric supplementation” as vitamin D intake that (a) exceeds the Dietary Reference Intakes (DRI) and (b) is implemented without testing for 25(OH)D. Systematic reviews queried electronic databases for publications related to these 14 clinical questions. The Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) methodology was used to assess the certainty of evidence and guide recommendations. The approach incorporated perspectives from a patient representative and considered patient values, costs and resources required, acceptability and feasibility, and impact on health equity of the proposed recommendations. The process to develop this clinical guideline did not use a risk assessment framework and was not designed to replace current DRI for vitamin D. Results The panel suggests empiric vitamin D supplementation for children and adolescents aged 1 to 18 years to prevent nutritional rickets and because of its potential to lower the risk of respiratory tract infections; for those aged 75 years and older because of its potential to lower the risk of mortality; for those who are pregnant because of its potential to lower the risk of preeclampsia, intra-uterine mortality, preterm birth, small-for-gestational-age birth, and neonatal mortality; and for those with high-risk prediabetes because of its potential to reduce progression to diabetes. Because the vitamin D doses in the included clinical trials varied considerably and many trial participants were allowed to continue their own vitamin D–containing supplements, the optimal doses for empiric vitamin D supplementation remain unclear for the populations considered. For nonpregnant people older than 50 years for whom vitamin D is indicated, the panel suggests supplementation via daily administration of vitamin D, rather than intermittent use of high doses. The panel suggests against empiric vitamin D supplementation above the current DRI to lower the risk of disease in healthy adults younger than 75 years. No clinical trial evidence was found to support routine screening for 25(OH)D in the general population, nor in those with obesity or dark complexion, and there was no clear evidence defining the optimal target level of 25(OH)D required for disease prevention in the populations considered; thus, the panel suggests against routine 25(OH)D testing in all populations considered. The panel judged that, in most situations, empiric vitamin D supplementation is inexpensive, feasible, acceptable to both healthy individuals and health care professionals, and has no negative effect on health equity. Conclusion The panel suggests empiric vitamin D for those aged 1 to 18 years and adults over 75 years of age, those who are pregnant, and those with high-risk prediabetes. Due to the scarcity of natural food sources rich in vitamin D, empiric supplementation can be achieved through a combination of fortified foods and supplements that contain vitamin D. Based on the absence of supportive clinical trial evidence, the panel suggests against routine 25(OH)D testing in the absence of established indications. These recommendations are not meant to replace the current DRIs for vitamin D, nor do they apply to people with established indications for vitamin D treatment or 25(OH)D testing. Further research is needed to determine optimal 25(OH)D levels for specific health benefits.

Abstract Introduction n this cross-validation study, the distributions of sleep biomarker-based neurodegenerative disorder (NDD) risk were evaluated across a spectrum of NDD patients and presumed controls which were independent of the model development dataset. Methods Variables that included age, time-REM, non-REM hypertonia, autonomic-activation index, spindle-duration, atypical-N3, time-supine, sleep-efficiency, relative-theta, and theta/alpha obtained with Sleep Profiler were used to train a 4-class machine learning algorithm that generated probabilities of NDD risk for the groups: Alzheimer’s dementia (AD), Lewy body disorder (LBD), prodromal synucleinopathy (pSYN based on REM sleep behavior disorder patients), and controls (CG). Records with CG output probabilities >70% were labeled Probably-normal, and from 45-70% Likely-normal with indications of a NDD added when the LBD, AD or pSYN risks exceeded approximately 25%. Similar thresholds were used to assign Likely- or Probable- LBD, AD, pSYN or Mixed based on the group probabilities. This cross-validation study was designed to use datasets that were independent of those used to train the classification algorithm. Thus, NDD risk distributions were evaluated in patients with mild cognitive impairment (MCI=71), Parkinson’s disease (PD=16), progressive supranuclear palsy (PSP=21) and control subjects (NC=41) with Mini-Mental State Exam scores>28 and/or normal for MCI by Petersen criteria. Results In the MCI group, NDD risk assignments were Probable-AD=26%, -Mixed=10%, -LBD=1%, Likely-AD= 7%, -Mixed=6%, -LBD=3%, -pSYN=1%, Likely-Normal indications-AD=9%, -pSYN=7%, -Mixed=4%, and Probably-Normal=26% In the PSP group, Probable-LBD=43%, -Mixed=29% and -pSYN=4%, Likely-Mixed=10%, Likely-Normal indications AD=10%, and Probably-Normal=4%. In the PD group, Probable-LBD=13%, -pSYN=13%, -AD=6%, Likely-Mixed=19%, -pSYN=6%, Likely-Normal Indications-pSYN=19%, -AD=12%, Likely-Normal=6% and Probably-Normal=6% In the NC group, 83% were assigned minimal NDD risk with Probably-Normal=70%, Likely-Normal plus indications=13%, but with Likely NDD=13% and Probable NDD=4%. Conclusion NDD risks were disbursed in a manner consistent with the range of severities expected In MCI and PD groups, with 25% exhibiting relatively normal sleep patterns. Over 70% of the PSP patients exhibited probable NDD risk, with patterns similar to those with LBD. The NC NDD risk distributions were consistent with those assigned to the CG used for model development. Support (if any) NIH grants R44AG050326, R44AG054256, RO1AG060477, R33AG064271, ULRR024150, R34AG056639.

Abstract Introduction In this pilot study, the diagnostic agreement for sleep biomarker-based neurodegenerative disorder (NDD) risk probabilities was evaluated in patients with Alzheimer’s disease dementia (AD), Lewy Body disease (LBD), and isolated REM sleep behavior disorder (iRBD) and controls with a Mini-Mental State Exam scores>28. Methods Sleep biomarkers recorded with the Sleep Profiler (Advanced Brain Monitoring, Inc) were used as inputs to a 4-class machine learning algorithm trained to assign NDD risk probabilities to AD=27, LBD=19, iRBD=15 and controls (CG=58). Input variables included age, time-REM, non-REM hypertonia, autonomic-activation index, spindle-duration, atypical-N3, time-supine, sleep-efficiency, relative-theta, and theta/alpha. Records with CG output probabilities >70% were labeled Probably-normal, and from 45-70% Likely-normal with indications of a NDD added when the LBD, AD or prodromal synucleinopathy (pSYN) risks exceeded approximately 25%. Similar thresholds were used to assign Likely- or Probable- LBD, AD, or pSYN based each of the group probabilities. Classification accuracies were evaluated in AD=37, LBD=19, iRBD=19 and CG=61 records. Longitudinal test-retest reliabilities were assessed for CG (n=45, range 8-56 months), and after six-months for LBD (n=10) and AD (n=9). Results In the AD group, NDD risk assignments were consistent with diagnoses=85%, with Probable-NDD=59%, Likely-NDD=11%, Normal plus AD/Mixed indications=15%, but with 5%=Probably-normal. In the LBD group, assigned risks were consistent with the diagnosis=79%, with Probable-NDD=74%, Normal with pSYN indications=5%, but with 11%=Probably-normal. In the iRBD group, Probable-NDD=42%, Normal plus pSYN indications=26% and Probably-normal=32%. In the CG group, 89% were assigned minimal NDD risks with Probably-normal=67%, Normal plus indications=22%, but with Likely NDD=8% and Probable NDD=3%. The AD test-retest reliability showed the same NDD classifications=78%, with slightly increasing=11% and decreased=11%. In the LBD group, the same NDD classifications were achieved=80%, with trending equivalence=10%, and decreasing severity=20%. The CG test-retest reliability showed the same NDD classifications=76%, with trending equivalence=22%, and increased severity=2%. Conclusion Consistencies between the diagnoses and assigned NDD risks and test-retest classification agreements were approximately 80% in the AD, LBD, and CG groups. In the iRBD group, the NDD risks were disbursed consistent with the range of expected severities. These results needed to be cross-validated in independent NDD datasets. Support (if any) NIH grants R44AG050326, R44AG054256, RO1AG060477, R33AG064271, ULRR024150, R34AG056639.

Abstract Introduction In this pilot study, sleep biomarker-based neurodegenerative disorder (NDD) risk was assessed in a clinical cohort of patients diagnosed with varying severity of obstructive sleep apnea (OSA). Methods Consecutive in-home multi-night Sleep Profiler records from a community sleep clinic were screened for age >54 years old. Cases with comorbid restless leg syndrome, hypersomnia, missing apnea-hypopnea indexes (AHI), AHI< 5 or single-night recordings were excluded. The 67 remaining records were 40% female, ages 63 + 7.4 years and up to 84 years old. NDD risk was assigned using a machine-learning algorithm combining age and nine sleep biomarkers to assign group probabilities: for Alzheimer’s disease, Lewy Body disease, prodromal synucleinopathy and controls (CG). Sleep biomarkers included: time-REM, non-REM hypertonia, autonomic-activation index, spindle-duration, atypical-N3, time-supine, sleep-efficiency, relative-theta, and theta/alpha. Those with CG probability score >70% were classified as “Probably-normal”. Those with CG probability between 45 - 70% were classified as “Likely-normal”. Insomnia severity >14 and a PHQ 9 > 5 were used as cutoffs for clinical insomnia and depression. Mann-Whitney U-tests were used to evaluate group differences. Results This cohort had 37% mild, 34% moderate, and 29% severe OSA. Self-reported comorbid insomnia and depression were present in 43%. Seventy-three percent of patients were classified as “Probably-normal”, 16% “Likely-normal”, 11% “Likely-NDD” or “Probable-NDD”. The “Probably-normal” group was younger than the rest of the cohort (62 + 6.2 years vs. 68 + 8.6 years, p< 0.01). Of those classified as “Probably-normal” (n=49), OSA was mild in 16, moderate in 17 and severe in 16. Mean AHI trended higher in the “Probably-normal” group than in those with elevated NDD risk (29 + 23.9 vs. 19 + 13.6 events/h, p=0.085). Conclusion Approximately 89% of the clinical cohort was classified as “Probably-normal” or “Likely-normal”. NDD risk was age-dependent. Interactions between OSA severity and NDD risk were not apparent in these findings, possibly related to group-wide effects. NDD risk, as measured by this model, did not appear to be adversely biased by untreated OSA. These results suggest a need for longitudinal studies to compare NDD risk in untreated OSA versus controls without sleep disordered breathing. Support (if any) NIH grants R44AG050326, R44AG054256, RO1AG060477, R33AG064271, ULRR024150, and R34AG056639.

BACKGROUND Mohs micrographic surgery efficiently treats skin cancer through staged resection, but surgeons' varying resection rates may lead to higher medical costs. OBJECTIVE To evaluate the cost savings associated with a quality improvement. MATERIALS AND METHODS The authors conducted a retrospective cohort study using 100% Medicare fee-for-service claims data to identify the change of mean stages per case for head/neck (HN) and trunk/extremity (TE) lesions before and after the quality improvement intervention from 2016 to 2021. They evaluated surgeon-level change in mean stages per case between the intervention and control groups, as well as the cost savings to Medicare over the same time period. RESULTS A total of 2,014 surgeons performed Mohs procedures on HN lesions. Among outlier surgeons who were notified, 31 surgeons (94%) for HN and 24 surgeons (89%) for TE reduced their mean stages per case with a median reduction of 0.16 and 0.21 stages, respectively. Reductions were also observed among outlier surgeons who were not notified, reducing their mean stages per case by 0.1 and 0.15 stages, respectively. The associated total 5-year savings after the intervention was 92 million USD. CONCLUSION The implementation of this physician-led benchmarking model was associated with broad reductions of physician utilization and significant cost savings.