Citations

Abstract Background In 2021, the American Academy of Physical Medicine and Rehabilitation established the Multi‐Disciplinary Post‐Acute Sequelae of SARS‐CoV‐2 Infection Collaborative to provide guidance from established Long COVID clinics for the evaluation and management of Long COVID. The collaborative previously published eight Long COVID consensus guidance statements using a primarily symptom‐based approach. However, Long COVID symptoms most often do not occur in isolation. Aims This compendium aims to equip clinicians with an efficient, up‐to‐date clinical resource for evaluating and managing adults experiencing Long COVID symptoms. The primary intended audience includes physiatrists, primary care physicians, and other clinicians who provide first‐line assessment and management of Long COVID symptoms, especially in settings where subspecialty care is not readily available. This compendium provides a holistic framework for assessment and management, symptom‐specific considerations, and updates on prevalence, health equity, disability considerations, pathophysiology, and emerging evidence regarding treatments under investigation. Because Long COVID closely resembles other infection‐associated chronic conditions (IACCs) such as myalgic encephalomyelitis/chronic fatigue syndrome, the guidance in this compendium may also be helpful for clinicians managing these related conditions. Methods Guidance in this compendium was developed by the collaborative's established modified Delphi approach. The collaborative is a multidisciplinary group whose members include physiatrists, primary care physicians, pulmonologists, cardiologists, psychiatrists, neuropsychologists, neurologists, occupational therapists, physical therapists, speech and language pathologists, patients, and government representatives. Over 40 Long COVID centers are represented in the collaborative. Results Long COVID is defined by the National Academies of Sciences, Engineering, and Medicine as “an IACC that occurs after SARS‐CoV‐2 infection and is present for at least 3 months as a continuous, relapsing and remitting, or progressive disease state that affects one or more organ systems.” The current global prevalence of Long COVID is estimated to be 6%. Higher prevalence has been identified among female gender, certain racial and ethnic groups, and individuals who live in nonurban areas. However, anyone can develop Long COVID after being infected with the SARS‐CoV‐2 virus. Long COVID can present as a wide variety of symptom clusters. The most common symptoms include exaggerated fatigue and diminished energy windows, postexertional malaise (PEM)/postexertional symptom exacerbation (PESE), cognitive impairment (brain fog), dysautonomia, pain/myalgias, and smell and taste alterations. Holistic assessment should include a traditional history, physical examination, and additional diagnostic testing, as indicated. A positive COVID‐19 test during acute SARS‐CoV‐2 infection is not required to diagnose Long COVID, and currently, there is no single laboratory finding that is definitively diagnostic for confirming or ruling out the diagnosis of Long COVID. A basic laboratory assessment is recommended for all patients with possible Long COVID, and consideration for additional labs and diagnostic procedures is guided by the patient's specific symptoms. Current management strategies focus on symptom‐based supportive care. Critical considerations include energy conservation strategies and addressing comorbidities and modifiable risk factors. Additionally, (1) it is essential to validate the patient's experience and provide reassurance that their symptoms are being taken seriously because many patients have had their symptoms dismissed by loved ones and clinicians; (2) physical activity recommendations must be carefully tailored to the patient's current activity tolerance because overly intense activity can trigger PEM/PESE and worsened muscle damage; and (3) treatment recommendations should be delivered with humility because there are many persistent unknowns related to Long COVID. To date, there are limited data to guide medication management specifically in the context of Long COVID. As such, medication use generally follows standard practice regarding indications and dosing, with extra attention to prioritize (1) patient preference via shared decision‐making and (2) cautious use of medications that may improve some symptoms (eg, cognitive/attention impairment) but may worsen other symptoms (eg, PEM/PESE). Numerous clinical trials are investigating additional treatments. The return‐to‐work process for individuals with Long COVID can be challenging because symptoms can fluctuate, vary in nature, affect multiple functional areas (eg, physical and cognitive), and often manifest as an “invisible disability” that may not be readily acknowledged by employers or coworkers. Clinicians can help patients return to work by identifying suitable workplace accommodations and resources, providing necessary documentation, and recommending occupational or vocational therapy when needed. If these efforts are unsuccessful and work significantly worsens Long COVID symptoms or impedes recovery, applying for disability may be warranted. Long COVID is recognized as a potential disability under the Americans with Disabilities Act. Conclusion To contribute to the overall health and well‐being for all patients, Long COVID care should be delivered in a holistic manner that acknowledges challenges faced by the patient and uncertainties in the field. For more detailed information on assessment and management of specific Long COVID symptoms, readers can reference the collaborative's symptom‐specific consensus guidance statements.

Abstract Introduction: Breast cancer genome-wide association studies (GWAS) have identified over 200 susceptibility loci, many replicated in diverse populations. However, cross-ancestry evaluation of breast cancer genetic architecture remains limited. We examined breast cancer genetic architecture using GWAS summary results from European (EUR; cases (ca) = 188,474, controls (co) = 96,201), East Asian (EAS; ca = 20,393, co = 86,329), African American (AA; ca = 9,235, co = 10,184), and US Hispanic/Latina and Latin American (H/L; ca = 2,396, co =7,468) studies. Methods: GWAS results were derived from the Breast Cancer Association Consortium, the African Ancestry Breast Cancer Genetics Consortium (AABCG), Biobank Japan, and a meta-analysis of five studies of H/L women with breast cancer. Linkage disequilibrium (LD) scores were generated for EUR, EAS, and AMR using the 1000 Genomes Project, while AA LD scores were derived from a subset of AABCG controls. Heritability was estimated for each ancestry group using LD score regression. Genetic correlations between populations were assessed via Popcorn. Polygenicity was analyzed using GENESIS; however, due to the limited sample size in the H/L studies, these estimates were restricted to AA, EAS, and EUR. Enrichment of heritability across regulatory elements was evaluated using stratified LD score regression across all populations. Results: The logit-scale heritability and corresponding standard error (SE) were 0.466 (0.066) for EAS, 0.501 (0.050) for EUR, 0.588 (0.360) for H/L, and 0.614 (0.095) for AA. The estimated number of independent susceptibility loci was 4,446 for EAS, 5,235 for EUR, and 8,308 for AA. Using a clumping and thresholding approach, an optimal set of common variants were projected to explain 38.6% (EUR), 39.4% (EAS), and 26.2% (AA) of genetic variance for samples of 100,000 cases and 100,000 controls with AUCs from corresponding estimated polygenic risk scores (PRSs) of 0.621 (EUR), 0.634 (EAS), and 0.611 (AA). Genetic correlations were strongest between EUR and EAS (ρ = 0.79, SE = 0.08) and EUR and H/L (ρ = 0.68, SE = 0.21), and weakest between AA and EAS (ρ = 0.42, SE = 0.14) and AA and H/L (ρ = 0.26, SE = 0.24). Among 73 genomic features, we found significant (P < 0.05/73) enrichment in heritability in EUR for ‘ancient promoter’ regions, transcription factor binding sites, H3K4me3, ‘super-enhancers’, H3K4me1, H3K27ac; in EAS for ‘super-enhancers’; and in AA for H3K27ac. No genomic features were significantly enriched in H/L, likely due to limited power. Conclusion: These findings suggest a shared breast cancer genetic architecture across diverse populations, as well as the potential for a similar level of breast cancer risk stratification by PRS in these populations. Expanding GWAS in underrepresented populations is essential to improve genetic risk predictions and foster equitable cancer prevention. Citation Format: James L. Li, Maria Zanti, Jacob Williams, Om Jahagirdar, Guochong Jia, Qiang Hu, Jean-Tristan Brandenburg, Li Yan, Weang-Kee Ho, Jingmei Li, José P. Miranda, Devika Godbole, Julie-Alexia Dias, Leila Dorling, Wenlong C. Chen, Nicholas Boddicker, Ying Wang, Alicia Martin, Martin J. Zhang, Yan Zhang, Joe Dennis, Esther M. John, Gabriela Torres-Mejia, Larry Kushi, Jeffrey Weitzel, Susan L. Neuhausen, Luis Carvajal-Carmona, Christopher Haiman, Elad Ziv, Laura Fejerman, Wei Zheng, Dezheng Huo, Douglas Easton, Nilanjan Chatterjee, Peter Kraft, Montserrat Garcia-Closas, Wendy Wong, Kyriaki Michailidou, Qianqian Zhu, Diptavo Dutta, Thomas U. Ahearn, Haoyu Zhang. Genetic architecture of breast cancer across diverse populations: Assessing heritability, genetic correlation, and polygenicity [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 1 (Regular Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_1):Abstract nr 2282.

Abstract Breast cancer risk assessment tools are widely used in clinical practice to guide decisions regarding screening timing and modality, lifestyle interventions, genetic testing, preventive therapy, and risk-reducing surgery. Although a number of tools designed for the general population are used in practice, they face a series of challenges including: (i) modest discriminatory ability due to lack of a unified model that flexibly incorporates a comprehensive set of risk factors; (ii) inability to produce subtype-specific risk estimates, relevant for tailoring screening and/or preventive strategies (e.g. prophylactic endocrine therapy that is effective only for hormone receptor positive tumors); (iii) lack of data from diverse populations to build models that work well for all women; and, (iv) scarcity of opportunities for comparative validation of different models. The Breast Cancer Risk Prediction Project (BCRPP), a collaboration currently including 20 prospective cohorts from the National Cancer Institute’s Cohort Consortium, is addressing these challenges by harmonizing, sharing, and analyzing data on over 1.8 million women, over 115, 000 of whom have developed breast cancer. The BCRPP is developing a comprehensive tool that will predict breast cancer risk, overall and by subtypes, across major racial and ethnic groups in the United States. This tool incorporates known and emerging risk factors (e.g. reproductive history, anthropometry, smoking, alcohol intake, medication use, mammography, family history, and measured genotypes). In parallel to model building and validation efforts, BCRPP investigators are developing privacy-preserving web and mobile interfaces to deliver the risk tools to patients and clinicians. Here we present descriptive data on participating cohorts (e.g. dates of enrollment, ages at enrollment, length of follow up, numbers of cases by subtype), summarize missing data patterns and our approach to model development and validation that accounts for heterogeneity in missingness patterns across cohorts, and describe data governance procedures and data sharing infrastructure (including pooled and federated analyses, to account for policy limitations on sharing individual data). Descriptive information and procedures for requesting and accessing data are available via the BCRPP data platform (https://epidataplatforms.cancer.gov/bcrpp/). Although originally assembled for risk model development, these data on a large and diverse sample of women with extensive harmonized risk factors and covariates can be a resource to address other outstanding questions in breast cancer epidemiology across time, the lifecourse, and diverse populations. Citation Format: Peter Kraft, Laura Beane-Freeman, Julie Palmer, Ellen O'Meara, Jeanine Genkinger, James Lacey, Thomas Rohan, Lauren Teras, Marian L. Neuhouser, Kala Visvanathan, Celine Vachon, Roger Milne, Christopher Haiman, Yu Chen, Heather Eliassen, Cari Kitahara, Katie O'Brien, Emily White, Garnet Anderson, I-Min Lee, Archie Campbell, Renee Fortner, Ylva Lagerros, Sven Sandin, Mia Gaudet, Montserrat Garcia-Closas, Nilanjan Chatterjee. The Breast Cancer Risk Prediction Project: a resource of 1.8 million women with diverse backgrounds from 20 prospective cohorts to improve breast cancer risk prediction and advance breast cancer epidemiology [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 1 (Regular Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_1):Abstract nr 3583.

Background: Pediatric thumb ulnar collateral ligament (UCL) injuries usually have osseous involvement presenting as a Salter-Harris III avulsion fracture from the base of the proximal phalanx. There is limited guidance about when surgical or non-surgical treatment is more appropriate. Methods: Patients with thumb bony UCL injuries who presented to a large pediatric hospital between 2007 and 2017 were retrospectively identified. Demographics, fracture pattern, treatment, clinical course, and outcomes were collected. Radiographic measurements included size and displacement of fracture fragment as a percentage of the proximal phalanx base articular surface. A classification system was developed incorporating clinical stability of the metacarpophalangeal joint and quantity of displacement. Results: Sixty-five patients were included (47 males and 18 females). The mean age at time of injury was 14.8 SD 1.9 yrs old. 46 (71%) injuries occurred during sporting activities. 50 (77%) patients underwent nonsurgical management with immobilization, and 15 (23%) patients were treated surgically with open reduction internal fixation. For patients treated surgically, the mean fragment size was 28.2% SD 6.8% of the articular surface compared to 14.3% SD 12.5% of those treated non-surgically (P<0.0001). The mean fracture displacement for surgically treated patients was 32.7% SD 19.0% compared to 11.4% SD 7.3% of those treated non-surgically (P<0.0001). Overall, 100% of patients reported they were able to return to their previous level of activity. Conclusion: Many pediatric thumb bony UCL injuries can be treated non-surgically. A classification system based upon joint stability and fracture displacement may help guide appropriate management of these injuries.

Background: Cervical cancer screening with a self-collected vaginal specimen for human papillomavirus (HPV) testing was approved by the U.S. Food and Drug Administration in May 2024, offering a potential solution to declining screening rates. Objective: We aimed to assess acceptability of clinic-based vaginal specimen self-collection for HPV testing and to evaluate associations between participants’ sociodemographics and their likelihood of choosing self-collection for future screening and the overall acceptability of using the Evalyn® brush device. We also evaluated associations between specific acceptability constructs and reported likelihood to use the device in the future and overall acceptability. Methods: Following self-collection of a vaginal specimen, participants completed an electronic survey that measured constructs from the Theoretical Framework of Acceptability. Associations were assessed using logistic regressions. The study was conducted at a colposcopy clinic in the Gynecology department of a midwestern academic medical center in the United States from November 2022 through July 2023. Results: Participants ( n = 81) reported high likelihood (98% likely or very likely) of choosing in-home self-collection for future screening and unanimity on overall acceptability (100% acceptable or completely acceptable) of using the device. More affirmative responses to measures on instruction understandability, ease of device use, understanding the device is used for cervical cancer screening, and perceiving self-collection improves screening rates were associated with a higher likelihood to choose self-collection for future screenings and overall acceptability of the device (all p values <0.05). Conclusion: Vaginal specimen self-collection for HPV testing was well-received in the studied population, with high acceptability and likelihood of uptake. Implementation efforts should provide user-friendly instructions and emphasize the benefits of self-collection for cervical cancer screening, particularly among people less likely to engage with clinician-collected speculum-based screening.

Abstract Nodular adrenocortical disease is an entity more commonly recognized in recent years. We present a case of bilateral adrenal nodular disease in a young woman with ACTH-independent Cushing syndrome. She was treated with medical therapies at her preference to avoid adrenal insufficiency (AI) from surgery. She developed intolerance to medical therapy. Cryoablation of the right adrenal nodule was performed after adrenal vein sampling identified the right adrenal as the dominant source of cortisol. Cortisol levels were normal while on medical therapy after cryoablation but quickly became elevated after discontinuing medical therapy. The patient was then treated with osilodrostat and ultimately developed medication-induced AI that has persisted for more than 3 years. Due to the increased availability of new medications to treat Cushing syndrome, we present our experience to educate endocrinology audiences about the unexpected responses to medications. Using osilodrostat (off-label) in this patient led to prolonged primary AI after 4 months of use and now presumed permanent AI 36 months after discontinuation of treatment.