Required Mental Health Evaluation Before Initiating Gender-Affirming Hormones: Trans and Nonbinary Perspectives.

Purpose: Gender-affirming hormones (hormones)-the use of sex hormones to induce desired secondary sex characteristics in transgender and nonbinary (TGNB) individuals-are vital health care for many TGNB people. Some hormone providers require a letter from a mental health provider before hormone initiation. We explore the perspectives of TGNB individuals regarding the impact of the letter requirement on their experience of care. Methods: We conducted semistructured interviews with 21 TGNB individuals who have sought or are receiving hormones. We purposively sampled respondents who were (n=12) and were not (n=8) required to provide a letter. An Advisory Board of transgender individuals guided the methodology. Interviews were transcribed verbatim and coded both inductively and deductively. Results: We identified three themes related to the letter requirement: (1) Mental health: While participants appreciated the importance of therapy, the letter requirement did not serve this purpose; (2) Trans identity: The process of obtaining a letter created doubt in participants' own transness, along with a resistance to the pathologization and conflation of mental illness with transness; and (3) Care relationships: The letter requirement negatively impacted the patient-provider relationship. Participants felt the need to self-censor or to perform a version of transness they thought the provider expected; this process decreased their trust in care professionals. Conclusion: A letter requirement did not improve mental health and had several negative consequences. Removal of this requirement will improve access to hormones and may paradoxically improve mental health.

One-year Thyroglobulin Levels as a Predictive Measure for Recurrence and Need for Continued Surveillance in Treated Differentiated Thyroid Cancer.

PURPOSE: Patients with differentiated thyroid cancer (DTC) undergo posttreatment surveillance for several years. We aim to better define an excellent response to therapy using thyroglobulin (TG) and thyroglobulin antibody (TGab) levels at 1-year to tailor appropriate length of surveillance. METHODS: Patients with DTC who underwent surgical treatment with or without adjuvant radioiodine therapy were followed with standard American Thyroid Association surveillance. TG and TGab levels at 1-year posttreatment were used to define 3 cohorts: undetectable TG (<0.5 ng/mL), detectable TG (≥0.5 ng/mL), and positive TGab (>1 IU/mL). The rates of structural recurrence and the trends of TG and TGab were compared. RESULTS: Of the 268 study patients at 1-year, 210 (78%) had undetectable TG, 29 (11%) had detectable TG, and 29 (11%) had positive TGab. The overall structural recurrence rate was 18/268 (7%): undetectable TG at 1 year, 3/210 (1%), detectable TG at 1-year, 11/29 (38%), and positive TGab at 1-year, 4/29 (13%). At the last follow-up, 196/210 (93%) patients with undetectable TG at 1-year continued to have undetectable TG levels. Regarding patients with detectable TG at 1-year, in 11/29 (38%), detectable TG was converted to undetectable TG at the last follow-up without additional treatments. Of those with positive TGab at 1 year, 6/29 (21%) had resolution of TGab and undetectable TG levels at the last follow-up without additional treatments. CONCLUSION: One year after treatment of DTC, TG levels <0.5 ng/mL, in the absence of TGab, are associated with an exceedingly low risk of recurrence suggesting that further surveillance may not be warranted.

Natural history of visceral branch artery dissections and the influence of concurrent aortic dissection on overall and intervention-free survival.

OBJECTIVE: Visceral branch artery dissection (VBAD) is uncommon and may occur with or without an associated aortic dissection (AD). We hypothesized that isolated VBAD would have a more benign clinical course than those with concurrent AD and compared survival outcomes stratified based on aortic involvement. METHODS: VBAD over a 5-year period were identified using International Classification of Diseases codes. Data related to patient demographics, comorbid conditions, clinical presentation, management (including procedural interventions), and survival were obtained from medical records. Anatomic imaging studies were reviewed to characterize anatomy, including the presence or absence of concurrent AD. Overall survival and intervention-free survival were evaluated using Kaplan-Meier and Cox proportional hazards models. RESULTS: A total of 299 VBAD were identified, 174 of which were isolated VBAD and 125 were associated with concurrent AD. Seventy-one percent of patients were men, 77% were White, and 85% were non-Hispanic. The mean age was 61.1 ± 14.4 years. The mean follow-up was 53.2 ± 50.0 months. The estimated overall survival was 88.2% and the estimated overall intervention-free survival was 55.6% at 12 months. Isolated VBAD had better overall survival than those with concurrent AD (69.2% vs 32.4%; P < .001). Concurrent AD was also associated with inferior intervention-free survival (57.5% vs 7.3%; P < .001). Acute presentation was associated with decreased intervention-free survival (86.1% vs 13.4%; P < .001). Acute presentation was also associated with decreased overall survival in patients with isolated VBAD (60.8% vs 80.0% at 180 months; P < .001) and inferior intervention-free survival (48.4% vs 69.5% at 180 months; P < .001) in the subgroup of patients with isolated VBAD. Multivariable Cox models identified that age (hazard ratio [HR]: 1.05, standard deviation [SD]: 0.02; P = .001) was associated with inferior survival and renal dissections (HR: 3.08, SD: 0.99; P = .001) or mesenteric and renal dissections (HR: 3.39, SD: 1.44; P = .004) were associated with inferior intervention-free survival. CONCLUSIONS: Isolated VBAD has superior overall and intervention-free survival to those associated with concurrent AD. The absence vs presence of aortic involvement is useful for risk stratification and may support tailored approaches to the frequency of imaging surveillance.

"You've Got Gratitude!"- A Multispecialty and Multi-institution Program Encouraging Expressions of Gratitude.

OBJECTIVE: Efforts to improve physician well-being have focused on gratitude, which predicts health and happiness. Despite reported benefits, expressions of gratitude in healthcare can seem infrequent. Here, we describe Gratitude-Grams, an intervention to cultivate expressions of gratitude throughout a department. METHODS/APPROACH: Piloted in our Department of Surgery and adopted by others, Gratitude-Grams employs a web-based platform (Qualtrics). Program feedback was solicited during teaching conferences using an anonymous department survey. RESULTS: Gratitude-Grams streamlines and encourages expressions of gratitude while minimizing maintenance, cost, and time. The platform has been highly utilized and well-received in our Department of Surgery. CONCLUSION: Expressing and receiving gratitude has been shown to be critical for well-being. Gratitude-Grams is a highly utilized, simple, and attainable system to support expressions of gratitude and is ready for rapid implementation.

Initiating gender-affirming hormones for transgender and non-binary people: A qualitative study of providers' perspectives on requiring mental health evaluations.

OBJECTIVE: Gender-affirming hormones (GAH)-the use of sex hormones to induce desired secondary sex characteristics in transgender individuals-is vital healthcare for many transgender people. Among prescribers of GAH, there is debate regarding the value of a universal requirement for an evaluation by a mental health provider prior to GAH initiation. The purpose of this qualitative study was to describe the range of attitudes and approaches to mental health evaluation among GAH providers in the United States. We analyzed the providers' attitudes and base our recommendations on this analysis. METHODS: We conducted semi-structured interviews with 18 healthcare providers who prescribe GAH across the United States. Participants were purposefully recruited using professional networks and snowball sampling to include those who require mental health evaluation and those who do not. We adapted domains from the Theoretical Domains Framework-a framework for understanding influences on health professional behavior-to inform the interviews and analysis. Guided by these domains, we iteratively coded text and identified theoretical relationships among the categories. RESULTS: While some felt a universal requirement for mental health "clearance" was necessary for the identification of appropriate candidates for GAH, others described this requirement as a form of "gatekeeping" that limits access to care. Themes we identified included providers' ability to ascertain gender identity; concern about mental illness; GAH provider and mental health provider expertise; and provider roles. All providers appreciated the potential advantages of mental health support during GAH treatment. CONCLUSION: Providers in our study practice on a continuum of care rather than adhering to strict rules about the requirement for mental health evaluation prior to GAH treatment. Where they fall on this continuum is influenced primarily by their perceptions of transgender identity and transition, and their interpretation of risk for significant mental illness and its association with transness. Providers who required universal evaluation by a mental health professional tended to hold essentialist, medicalized, and binary ideas of gender and transness.

High-throughput splicing assays identify missense and silent splice-disruptive POU1F1 variants underlying pituitary hormone deficiency.

Pituitary hormone deficiency occurs in ∼1:4,000 live births. Approximately 3% of the cases are due to mutations in the alpha isoform of POU1F1, a pituitary-specific transcriptional activator. We found four separate heterozygous missense variants in unrelated individuals with hypopituitarism that were predicted to affect a minor isoform, POU1F1 beta, which can act as a transcriptional repressor. These variants retain repressor activity, but they shift splicing to favor the expression of the beta isoform, resulting in dominant-negative loss of function. Using a high-throughput splicing reporter assay, we tested 1,070 single-nucleotide variants in POU1F1. We identified 96 splice-disruptive variants, including 14 synonymous variants. In separate cohorts, we found two additional synonymous variants nominated by this screen that co-segregate with hypopituitarism. This study underlines the importance of evaluating the impact of variants on splicing and provides a catalog for interpretation of variants of unknown significance in POU1F1.

Massively parallel functional testing of MSH2 missense variants conferring Lynch syndrome risk.

The lack of functional evidence for the majority of missense variants limits their clinical interpretability and poses a key barrier to the broad utility of carrier screening. In Lynch syndrome (LS), one of the most highly prevalent cancer syndromes, nearly 90% of clinically observed missense variants are deemed "variants of uncertain significance" (VUS). To systematically resolve their functional status, we performed a massively parallel screen in human cells to identify loss-of-function missense variants in the key DNA mismatch repair factor MSH2. The resulting functional effect map is substantially complete, covering 94% of the 17,746 possible variants, and is highly concordant (96%) with existing functional data and expert clinicians' interpretations. The large majority (89%) of missense variants were functionally neutral, perhaps unexpectedly in light of its evolutionary conservation. These data provide ready-to-use functional evidence to resolve the ∼1,300 extant missense VUSs in MSH2 and may facilitate the prospective classification of newly discovered variants in the clinic.