Citations

The underlying immunopathogenesis of inflammatory arthritis (IA) immune-related adverse event (irAE) remains obscure. Unlike rheumatoid arthritis (RA), where autoantibodies and B cell dysfunction are central features, the contribution of humoral immunity to IA-irAE is unclear. Here, we performed immunophenotyping of peripheral blood from patients with IA-irAE and compared them with patients with seronegative RA, immune checkpoint inhibition–treated patients without irAE, and healthy controls. IA-irAE was marked with increased cytotoxic gene expression and metabolic activation in T cells and reduced CXCR3 and CCR6 expression in CD4 + T cells. Contrary to seronegative RA, patients with IA-irAE displayed no substantial elevation in autoantibody levels or atypical CD11c + CD21 − B cells. IA-irAE was further characterized by elevated levels of interleukin-6 (IL-6), IL-12, and type I interferon, which correlated with the T cell activation phenotypes. Together, our findings define IA-irAE as a disease with certain immunological features distinctive from RA, representing a potentially T cell–driven, autoantibody-independent autoimmunity. These results offer insights into immune tolerance breakdown and therapeutic targeting in irAEs.

Abstract Purpose Consensus recommendations and guidelines for reporting quantitative research in health professions education (HPE) research are lacking. This study synthesizes available quantitative reporting recommendations and guidelines to present a harmonized framework and derive quantitative standards for reporting HPE research. Method The authors identified existing standards, recommendations, and guidelines from peer-reviewed scientific journals in medicine, education, and social sciences by searching PubMed, Web of Science, and Google from August 2006 through April 2025. The authors also requested input from experts in HPE (scholars and journal editors) via electronic communication over 6 months (November 2024 to April 2025). The articles identified were then used to synthesize and generate an initial list of standards for reporting quantitative research in HPE. Two authors reviewed each article to rate its alignment with HPE research. All authors independently evaluated the full list of standards and discussed them as a group for their relevance and alignment for reporting in HPE; all authors also made recommendations for each standard (to report as is, report but modify, or drop). The group subsequently reviewed and collectively reached consensus on the final set of quantitative reporting standards. Results The authors reviewed a total of 34 articles, with 19 identified as having alignment with HPE quantitative research standards. Mean interrater agreement among author pairs was 98% (kappa = .96). Authors initially generated 40 reporting standards, of which 18 (45%) were modified and 1 (3%) was identified to be dropped. The final set of quantitative guidelines consisted of 39 standards, with each standard nested in one of 28 topic areas. Conclusions The quantitative reporting standards identified in this study provide guidance to ensure rigor in reporting expectations for HPE research. These standards may also facilitate critical appraisal of articles and enhance the quality and impact of quantitative HPE research.

Background: Distal femoral osteotomy (DFO) may be performed via either a lateral opening-wedge (LOW) or medial closing-wedge (MCW) osteotomy with meaningful clinical improvements; however, the effects of each DFO technique on leg length have not been well characterized. Purpose: To (1) validate a radiographic measurement technique to predict leg length changes after DFO and (2) compare the change in leg length after DFO for the LOW and MCW techniques. Study Design: Cohort study; Level of evidence, 3. Methods: Preoperative and postoperative full-length standing radiographs obtained from patients who underwent DFO at 1 of 2 academic medical centers were evaluated. The region on the medial (for LOW) or lateral (for MCW) distal femur cortex that would be the “hinge point” during DFO was identified on the radiographs. The distance from the center of the femoral head to the hinge point ( A ), the distance from the hinge point to the center of the talus ( B ), and the resultant angle (α) were measured. The equation presented within the text was used to plot the predicted leg length changes corresponding to the change in alpha angle produced by DFO. Comparisons were made between (1) the predicted and measured leg length changes after DFO and (2) the measured leg length change after LOW versus MCW osteotomies. Results: For both LOW (n = 10) and MCW (n = 10) osteotomies, the predicted leg length change was equivalent to the true change measured on postoperative radiographs (LOW: P = .16; MCW: P = .85). There was a mean lengthening of 0.85 mm (range, 0.5-1.3 mm) for every 1° of mechanical axis correction with LOW DFO, compared to a mean shortening of 0.45 mm (range, 0.1-1.4 mm) per 1° of MCW correction. Conclusion: Preoperative radiographic imaging can be used to predict leg length change after DFO with high reliability. Surgeons can expect approximately 0.85 mm of lengthening per 1° of DFO correction when performing LOW osteotomies, compared to 0.45 mm of shortening per 1° of correction for MCW osteotomies. However, the most accurate prediction results from patient-specific calculations.

Importance The management of infectious and inflammatory lesions of the breast remains controversial. The expert panel focused on management recommendations for 3 of the most common infectious breast conditions, as very few evidence-based guidelines for the management of these conditions exist. Observations Clinicians should distinguish between infectious and noninfectious lactational mastitis (LM) because the former often requires interventions whereas the latter requires supportive care only. Patients with infectious LM often have thick fluid collections that are not amenable to aspiration and usually require a stab incision with drain placement (but no packing) to resolve the infection. Operative drainage is only required if the patient cannot tolerate an office procedure. If a phlegmon is present, antibiotics should be prescribed for at least 10 days. The diagnosis of granulomatous mastitis (GM) requires pathology confirmation with characteristic findings on core biopsy. Cystic neutrophilic granulomatous mastitis (CNGM) is a specific form of GM associated with a granulomatous reaction to Corynebacterium infection and should be empirically treated with doxycycline. For patients without findings characteristic of CNGM and no other associated bacterium identified, there is no role for empiric antibiotic use. Granulomatous mastitis cases often recur and can take up to 18 months to resolve. Patients who have GM cases with worsening symptoms should be treated with repeated intralesional steroid injections; surgical excision or repeated aspirations should be avoided. Cases refractory to intralesional steroid injection may require oral steroids or even advanced biologic agents such as methotrexate or azathioprine. Periductal mastitis with squamous metaplasia of lactiferous ducts (PDM-SMOLD) is a distinct entity from other periductal mastitis cases that can present with recurrent abscesses and should be treated with antibiotics and aspiration for fluid collections. Operative excision for PDM-SMOLD is required for those patients who present with a fistula or recurrent episodes typically using a radial incision to remove the diseased ducts within and below the nipple. Conclusions and Relevance Evidence-informed, consensus-, and expert opinion–based guidelines for the management of infectious and inflammatory conditions of the breast were developed. Clinicians can use these guidelines to appropriately manage these conditions for which clinical care often varied in the past.

Abstract Professional identity is defined as the attitudes, behaviors, values, and experiences by which individuals define themselves in a professional role and is influenced by socialization during training and in the workplace. As professional identity develops and is integrated with one's personal identities, it allows an individual to think, act, and feel like a member of their chosen profession and to develop a sense of meaning, confidence, and satisfaction in their work. Conflicts may arise due to perceived differences between one's professional identity and the collective identity of the profession, resulting in stress, burnout, and attrition, all of which can negatively impact patient care and the collective identity of the genetic counseling profession. Using Social Identity Theory (SIT) as a theoretical framework to develop the semi‐structured interview protocol, recorded interviews were conducted with 50 genetic counselors who were purposefully sampled to ensure diversity of personal demographics (gender, race/ethnicity, sexual orientation, disability, and caregiver status), as well as years, settings, and roles in genetic counseling practice. Transcripts were coded and subjected to codebook thematic analysis using NVivo. Genetic counselors described their professional identity in terms of who they are (characteristics and attributes), what they do (actions and skills), and what they have (training and knowledge). The majority of participants had a multidimensional perspective of what it means to be a genetic counselor, noting the transferability of their skills to a broad set of roles and settings, which supported their sense of professional identity, particularly for those who were no longer seeing patients. Yet many expressed tension with the collective identity of the profession. Expanded opportunities for genetic counselors to work in new settings and roles require review and revision of key professional documents to ensure they are reflective of the collective identity of the genetic counseling profession.

Abstract Context Crinecerfont, a first-in-class corticotropin-releasing factor type 1 receptor antagonist, is FDA-approved as an adjunct to the physiologic glucocorticoid (GC) required to treat the underlying adrenal insufficiency in patients (≥4 years old) with classic congenital adrenal hyperplasia (CAH). By reducing elevated adrenocorticotropic hormone, crinecerfont controls excess adrenal androgens, thereby enabling lower GC doses. However, there are no published recommendations for how to reduce supraphysiologic GC doses after initiating crinecerfont. This manuscript aims to provide a framework developed by experienced endocrinologists for reducing supraphysiologic GC doses in patients taking crinecerfont. Evidence Acquisition An experienced panel of 11 endocrinologists discussed strategies and considerations when reducing GC doses and developed an algorithm to guide GC dose reductions after introducing crinecerfont in adults with CAH. Evidence Synthesis Approaches to GC reduction should be individualized based on the patient's therapeutic goals, cortisol needs, lifestyle preferences, and the clinician's experience to set appropriate targets for clinical parameters, androgens, and GC dose regimen. In general, GC doses should be reduced gradually to minimize the risks of developing symptoms of GC withdrawal or adrenal insufficiency. GC doses should be adjusted to the lowest level needed to maintain androgens at goal, without reducing below what is needed for cortisol replacement. Practical considerations during GC dose reduction include switching from longer- to shorter-acting GCs (eg, from dexamethasone to hydrocortisone), optimizing dose distribution to mimic normal circadian cortisol exposure, and consolidating or eliminating doses to improve adherence. Conclusion This framework for reducing supraphysiologic GC doses in adult patients taking crinecerfont may become increasingly relevant as treatment of CAH shifts toward physiologic GC replacement with adjunctive control of adrenal androgens.

Abstract Background The incidence of gastroesophageal cancer diagnosed at ages younger than 50 years is increasing. Assessment of the clinicopathologic and molecular characteristics of these cancers is limited currently. Methods This analysis used Tempus’ clinicogenomic database to compare patients diagnosed with gastroesophageal cancer at ages younger than 50 vs 50 years and older who completed tumor molecular profiling between December 2017 and July 2024. The spectrum of biomarkers, somatic alterations, and germline alterations were compared between those diagnosed with gastroesophageal cancer at ages younger than 50 years and those aged 50 years and older, and a multivariate analysis was conducted to identify factors associated with longer survival. Results Among 5863 gastroesophageal cancer patients, 785 had gastroesophageal cancer diagnosed at ages younger than 50 years. There were more females (35% vs 25%, P < .001) and fewer White patients (69% vs 80%, P < .001) with gastroesophageal cancer at ages younger than 50 years. Fewer tumors of patients with gastroesophageal cancer at ages younger than 50 years had high tumor mutational burden (3.2% vs 10.2%, P < .001) or high microsatellite instability (1.7% vs 5.1%, P < .001), but there was no difference in PD-L1 positivity (49% vs 51%, P = .3). Higher incidence of somatic CDH1 mutations was seen in those with gastroesophageal cancer at ages younger than 50 years (16.1% vs 6.6%, q < 0.001) with lower incidence of TP53 (65.6% vs 74.1%), CDKN2A (12.5% vs 19.8%), and KRAS (11.7% vs 18.3%, P < .001 for all) alterations. The most statistically significant germline difference was higher incidence of CDH1 (2.2% vs 0.3%, q = 0.001) and TP53 (0.6% vs 0%, q = 0.039) alterations among those with gastroesophageal cancer at ages younger than 50 years. Median survival for patients with metastatic disease was longer for gastroesophageal cancer at ages younger than 50 years (11 vs 8.5 months, P = .002), and gastroesophageal cancer at ages younger than 50 years, ERBB2 amplification, and high microsatellite instability were associated with superior survival. Conclusions Unique molecular and germline profiles were seen in patients with gastroesophageal cancer at ages younger than 50 years, which may suggest differences in causal factors yet undiscovered.