The Tissue Systems Pathology Test Outperforms Pathology Review in Risk Stratifying Patients With Low-Grade Dysplasia.

BACKGROUND & AIMS: Low-grade dysplasia (LGD) is associated with an increased risk of progression in Barrett's esophagus (BE); however, the diagnosis of LGD is limited by substantial interobserver variability. Multiple studies have shown that an objective tissue systems pathology test (TissueCypher Barrett's Esophagus Test, TSP-9), can effectively predict neoplastic progression in patients with BE. This study aimed to compare the risk stratification performance of the TSP-9 test vs benchmarks of generalist and expert pathology. METHODS: A blinded cohort study was conducted in the screening cohort of a randomized controlled trial of patients with BE with community-based LGD. Biopsies from the first endoscopy with LGD were assessed by the TSP-9 test and independently reviewed by 30 pathologists from 5 countries per standard practice. The accuracy of the test and the diagnoses in predicting high-grade dysplasia (HGD) and esophageal adenocarcinoma (EAC) were compared. RESULTS: A total of 154 patients with BE (122 men), mean age 60.9 ± 9.8 years were studied. Twenty-four patients progressed to HGD/EAC within 5 years (median time of 1.7 years) and 130 did not progress to HGD/EAC within 5 years (median 7.8 years follow-up). The TSP-9 test demonstrated higher sensitivity (71% vs mean 63%, range 33%-88% across 30 pathologists), than the pathology review in detecting patients who progressed (P = .01186). CONCLUSIONS: The TSP-9 test outperformed the pathologists in risk stratifying patients with BE with LGD. Care guided by the test can provide an effective solution to variable pathology review of LGD, improving health outcomes by upstaging care to therapeutic intervention for patients at high risk for progression, while reducing unnecessary interventions in low-risk patients.

Sexual and gender minority content in undergraduate medical education in the United States and Canada: current state and changes since 2011.

PURPOSE: To characterize current lesbian, gay, bisexual, transgender, queer, and intersex (LGBTQI +) health-related undergraduate medical education (UME) curricular content and associated changes since a 2011 study and to determine the frequency and extent of institutional instruction in 17 LGBTQI + health-related topics, strategies for increasing LGBTQI + health-related content, and faculty development opportunities. METHOD: Deans of medical education (or equivalent) at 214 allopathic or osteopathic medical schools in Canada and the United States were invited to complete a 36-question, Web-based questionnaire between June 2021 and September 2022. The main outcome measured was reported hours of LGBTQI + health-related curricular content. RESULTS: Of 214 schools, 100 (46.7%) responded, of which 85 (85.0%) fully completed the questionnaire. Compared to 5 median hours dedicated to LGBTQI + health-related in a 2011 study, the 2022 median reported time was 11 h (interquartile range [IQR], 6-16 h, p < 0.0001). Two UME institutions (2.4%; 95% CI, 0.0%-5.8%) reported 0 h during the pre-clerkship phase; 21 institutions (24.7%; CI, 15.5%-33.9%) reported 0 h during the clerkship phase; and 1 institution (1.2%; CI, 0%-3.5%) reported 0 h across the curriculum. Median US allopathic clerkship hours were significantly different from US osteopathic clerkship hours (4 h [IQR, 1-6 h] versus 0 h [IQR, 0-0 h]; p = 0.01). Suggested strategies to increase content included more curricular material focusing on LGBTQI + health and health disparities at 55 schools (64.7%; CI, 54.6%-74.9%), more faculty willing and able to teach LGBTQI + -related content at 49 schools (57.7%; CI, 47.1%-68.2%), and more evidence-based research on LGBTQI + health and health disparities at 24 schools (28.2%; CI, 18.7%-37.8%). CONCLUSION: Compared to a 2011 study, the median reported time dedicated to LGBTQI + health-related topics in 2022 increased across US and Canadian UME institutions, but the breadth, efficacy, or quality of instruction continued to vary substantially. Despite the increased hours, this still falls short of the number of hours based on recommended LGBTQI + health competencies from the Association of American Medical Colleges. While most deans of medical education reported their institutions' coverage of LGBTQI + health as 'fair,' 'good,' or 'very good,' there continues to be a call from UME leadership to increase curricular content. This requires dedicated training for faculty and students.

An Automated Tissue Systems Pathology Test Can Standardize the Management and Improve Health Outcomes for Patients With Barrett's Esophagus.

INTRODUCTION: Low-grade dysplasia (LGD) in Barrett's esophagus (BE) is associated with an increased risk of progression to high-grade dysplasia or esophageal adenocarcinoma. However, because of substantial interobserver variability in the diagnosis of LGD, a patient's management plan and health outcome depend largely on which pathologist reviews their case. This study evaluated the ability of a tissue systems pathology test that objectively risk stratifies patients with BE (TissueCypher, TSP-9) to standardize management in a manner consistent with improved health outcomes for patients with BE. METHODS: A total of 154 patients with BE with community-based LGD from the prospectively followed screening cohort of the SURF trial were studied. Management decisions were simulated 500 times with varying generalist (n = 16) and expert (n = 14) pathology reviewers to determine the most likely care plan with or without use of the TSP-9 test for guidance. The percentage of patients receiving appropriate management based on the known progression/nonprogression outcomes was calculated. RESULTS: The percentage of patients with 100% of simulations resulting in appropriate management significantly increased from 9.1% for pathology alone, to 58.4% when TSP-9 results were used with pathology, and further increased to 77.3% of patients receiving appropriate management when only TSP-9 results were used. Use of the test results also significantly increased the consistency of management decisions for patients when their slides were reviewed by different pathologists ( P < 0.0001). DISCUSSION: Management guided by the TSP-9 test can standardize care plans by increasing the early detection of progressors who can receive therapeutic interventions, while also increasing the percentage of nonprogressors who can avoid unnecessary therapy and be managed by surveillance alone.

Examining Differences in Substance Use Outcomes and Related Correlates among Transfeminine and Transmasculine Adults Using the 2017 New York State Patient Characteristics Survey.

Background: Transgender persons in the U.S. experience high levels of violence and discrimination which have been linked to adverse substance use outcomes. Despite transgender women's higher exposure to such deleterious events compared to transgender men, studies have often aggregated both transgender women and men, obfuscating potentially unique differences between these groups. The current study, guided by the Minority Stress Model, examines differences in substance use outcomes and related correlates among transfeminine and transmasculine adults. Methods: A secondary data analysis was conducted using the 2017 Patient Characteristics Survey of public mental health facilities in the state of New York (N = 1387). Controlling for theoretically relevant factors, logistic regression models were estimated to examine differences between transfeminine and transmasculine adults in alcohol-related disorder (ARD) and drug use-related disorder (DURD) diagnoses, and tobacco use. Correlates of substance use disparities were also examined within gender identity groups. Results: Overall, 35% of participants were documented as using tobacco products whereas 14 and 19% were diagnosed with ARDs and DURDs, respectively. Transfeminine participants were 1.44-times more likely to be diagnosed with ARDs relative to transmasculine adults. Compared to transmasculine and White participants, transfeminine and Black participants were 1.64- and 1.59-times more likely to be diagnosed with DURDs. Conclusions: Recognizing the observed higher hazardous substance use risk among transfeminine and Black participants, findings indicate the potential role of minority stress in health outcomes of stigmatized communities. Our findings emphasize the need for identifying prevention and treatment strategies aimed at mitigating the implications of minority stress.

Comparison of faculty and student perceptions of sexual and gender minority content in a preclerkship medical curriculum.

BACKGROUND: Sexual and gender minority (SGM) persons experience stark health disparities. Efforts to mitigate disparities through medical education have met some success. However, evaluations have largely focused on subjective perspectives rather than objective measures. This study aimed to quantify Boston University School of Medicine's sexual and gender minority (SGM) education through surveys of course directors (CDs) and medical students regarding where SGM topics were taught in the preclerkship medical curriculum. Responses were compared to identify concordance between faculty intention and student perceptions regarding SGM education. METHODS: A cross-sectional survey was distributed to preclerkship CDs and current medical students in Spring 2019 and 2021, respectively, regarding where in the mandatory preclerkship curriculum CDs deliberately taught and where first- and second-year students recalled having learned 10 SGM topic domains. RESULTS: 64.3% of CDs (n = 18), 47.0% of the first-year class (n = 71), and 67.3% of the second-year class (n = 101) responded to the surveys. Results indicate that, as anticipated, deliberate SGM teaching correlates with greater student recall as students recalled topics that were reported by CDs as intentionally taught at a significantly higher rate compared to those not intentionally taught (32.0% vs. 15.3%; p < 0.01). Students most commonly recalled learning SGM-related language and terminology, which is likely partly but not entirely attributed to curricular modifications and faculty development made between distribution of the faculty and student surveys, indicating the importance of all faculty being trained in appropriate SGM terminology and concepts. Discordance between faculty intention and student recall of when topics were taught reveals opportunities to enhance the intentionality and impact of SGM teaching. CONCLUSIONS: Students perceive and recall SGM content that is not listed as learning objectives, and all faculty who utilize this material in their teachings should receive foundational training and be thoughtful about how information is framed. Faculty who intentionally teach SGM topics should be explicit and direct about the conclusions they intend students to draw from their curricular content.

Real-World Evidence Shows Clinicians Appropriately Use the Prognostic 40-Gene Expression Profile (40-GEP) Test for High-Risk Cutaneous Squamous Cell Carcinoma (cSCC) Patients.

Treatment decisions for patients with cutaneous squamous cell carcinoma (cSCC) are traditionally based upon clinicopathologic risk factors and staging systems. Due to the accuracy limitations of these resources in predicting poor outcomes, there is a clinically significant need for more accurate methods of risk assessment. The 40-gene expression profile (40-GEP) test was developed to augment metastatic risk prediction of high-risk cSCC patients and has been validated in two independent, multi-center studies involving over 1,000 patients. This study substantiates that the 40-GEP is appropriately utilized by clinicians and that the personalized risk-stratification results are impactful in guiding risk-aligned patient management.

Enhanced metastatic risk assessment in cutaneous squamous cell carcinoma with the 40-gene expression profile test.

Aim: To clinically validate the 40-gene expression profile (40-GEP) test for cutaneous squamous cell carcinoma patients and evaluate coupling the test with individual clinicopathologic risk factor-based assessment methods. Patients & methods: In a 33-site study, primary tumors with known patient outcomes were assessed under clinical testing conditions (n = 420). The 40-GEP results were integrated with clinicopathologic risk factors. Kaplan-Meier and Cox regression analyses were performed for metastasis. Results: The 40-GEP test demonstrated significant prognostic value. Risk classification was improved via integration of 40-GEP results with clinicopathologic risk factor-based assessment, with metastasis rates near the general cutaneous squamous cell carcinoma population for class 1 and ≥50% for class 2B. Conclusion: Combining molecular profiling with clinicopathologic risk factor assessment enhances stratification of cutaneous squamous cell carcinoma patients and may inform decision-making for risk-appropriate management strategies.

Plain language summary Cutaneous squamous cell carcinoma is a common skin cancer, with approximately 2 million cases diagnosed each year in the USA. Because substantial numbers of patients experience metastasis, which can result in death, accurate metastatic risk assessment is important. Clinicians use clinicopathologic factors to determine risk for disease progression. However, traditional methods miss pinpointing many patients who experience metastasis and sometimes categorize patients as at risk who do not develop metastasis, indicating that additional tools are needed. A molecular test, the 40-gene expression profile (40-GEP), was developed to predict metastatic risk based on the biology of the tumor. This study demonstrates that the 40-GEP, either as an independent tool or together with traditional methods, accurately identifies patients' risk of metastasis. Using the 40-GEP could improve patient management to improve patient outcomes.

The 31-gene expression profile stratifies recurrence and metastasis risk in patients with cutaneous melanoma.

Aim: Sentinel node biopsy is a prognostic indicator of melanoma recurrence. We hypothesized that adding the primary melanoma molecular signature from the 31-gene expression profile (31-GEP) test could refine the risk of recurrence prognosis for patients with stage I-III melanoma. Materials & methods: Four hundred thirty-eight patients with stage I-III melanoma consecutively tested with the 31-GEP were retrospectively analyzed. The 31-GEP stratified patients as low-risk (Class 1A), intermediate-risk (Class 1B/2A) or high risk (Class 2B) of recurrence or metastasis. Results: The 31-GEP significantly stratified patient risk for recurrence-free survival (p < 0.001), distant metastasis-free survival (p < 0.001) and melanoma-specific survival (p < 0.001) and was a significant, independent predictor of metastatic recurrence (hazard ratio: 5.38; p = 0.014). Conclusion: The 31-GEP improves prognostic accuracy in stage I-III melanoma.

Lay abstract Cutaneous melanoma is a type of skin tumor affecting 100,000 new patients each year. Even with the best tools available today, knowing which patients will die from their cancer can be challenging. Using individual tumors from over 400 patients, we analyzed the expression of 31 genes from each tumor. Doing this helped us split the patients into groups who are more or less likely to die from their tumor. By combining this technique with current medical practices and guidelines, we hope to help identify which patients may or may not benefit from more intense therapies.

Web Exclusive. Annals Graphic Medicine - Morning Thoughts on Day 7 of COVID-19 Social Isolation.

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Caring for the Transgender Patient: Grand Rounds Discussion From Beth Israel Deaconess Medical Center.

The term transgender refers to persons whose gender identity is different from that recorded at birth. Similar to other marginalized populations, transgender patients commonly experience discrimination in the health care setting, and they may not have access to medical professionals who can provide competent care. In addition to primary medical and preventive health care, transgender patients need access to gender-affirming interventions, including hormone therapy and surgeries. In 2017, the Endocrine Society updated its clinical practice guideline for the care of transgender persons on the basis of the best available evidence from systematic reviews and individual studies. Among its general requirements for adolescents and recommendations for adults were the following: Involvement of a mental health professional who is knowledgeable about the diagnostic criteria for gender dysphoria and criteria for gender-affirming treatment, has training and experience in assessing psychopathology, and is willing to participate in ongoing care. Hormone therapy should be offered to transgender adult patients, with levels maintained within the normal range for gender identity and treatment appropriately monitored. Clinicians involved in the care of transgender adult patients should be knowledgeable about diagnostic criteria for gender dysphoria/gender incongruence, the use of medical and surgical gender-affirming interventions, and appropriate monitoring for reproductive organ cancer risk. Here, 2 clinicians with expertise in this area debate whether psychological evaluation is warranted in a transgender patient requesting gender-affirming hormones or surgery, the potential risks and benefits of estrogen therapy, and the role of the primary care practitioner in the care of transgender persons.

"They Dumped Me Like Trash": The Social and Psychological Toll of Victimization on Latino Day Laborers' Lives.

Although recent rhetoric links undocumented immigrants to criminality, reports indicate undocumented immigrants commit less crime than their native-born counterparts and that this vulnerable group may be at increased risk for criminal victimization. Immigrants living in new immigrant settlement cities may be particularly at risk for exposure to criminal victimization due to the vulnerabilities associated with a lack of an established Latino community and limited availability of culturally appropriate social services to provide support. This ethnographic study examines the experiences of victimization and its social and psychological toll of a street-recruited sample of Latino day laborers (LDLs) (N = 25) living and working in Baltimore, a new immigrant settlement city. Findings elucidate and describe the specific types of victimization experienced by LDLs, including workplace victimization (wage theft, abandonment at the jobsite, poor working conditions, verbal abuse) and street-level victimization (assault and robbery), as well as reveal the social and psychological toll of victimization (sociocultural alienation, despair or desesperación, and problem drinking) on their lives. Findings have implications for community psychology, through research and practice, as they provide insights for prevention and intervention within the intersection of structural vulnerability (i.e., undocumented immigration status), violence, and mental health.

Prefrontal Cortex Dysfunction in Fragile X Mice Depends on the Continued Absence of Fragile X Mental Retardation Protein in the Adult Brain.

Fragile X Syndrome (FX) is generally considered a developmental disorder, arising from a mutation that disrupts the transcription of Fragile X Mental Retardation Protein (FMRP). However, FMRP regulates the transcription of other proteins and participates in an unknown number of protein-protein interactions throughout life. In addition to known developmental issues, it is thus likely that some dysfunction is also due to the ongoing absence of FMRP. Dissociating dysfunction due to developmental dysregulation from dysfunction due to the continued absence of FMRP is necessary to understand the different roles of FMRP and to treat patients effectively throughout life. We show here that FX model mice display substantial deficits in a PFC-dependent task. We then use conditional knock-out mice to eliminate FMRP only in the PFC alone of adult mice. We observe an increase in the proportion of nonlearners and a delay in the onset of learning in both FX and conditional knock-out mice. The results suggest that these deficits (1) are due to the absence of FMRP in the PFC alone and (2) are not the result of developmental dysregulation. Furthermore, PFC-associated deficits are rescued by initiating production of FMRP in adult conditional restoration mice, suggesting that PFC dysfunction may persist as long as FMRP is absent and therefore can be rescued after development. The data suggest that it is possible to dissociate the roles of FMRP in neural function from developmental dysregulation, and that PFC function can be restored in the adult FX brain.SIGNIFICANCE STATEMENT The absence of Fragile X Mental Retardation Protein (FMRP) from birth results in developmental disabilities and lifelong impairments. We show here that in mouse models PFC dysfunction in Fragile X Syndrome (FX) can be attributed to the continued absence of FMRP from the PFC, independent of FMRP status during development. Furthermore, initiation of FMRP production in the PFC of adult FX animals rescues PFC function. The results suggest that at least some FX-specific neurological defects can be rescued in the adult FX brain after development.

Nanoelectronic Coating Enabled Versatile Multifunctional Neural Probes.

Brain function can be best studied by simultaneous measurements and modulation of the multifaceted signaling at the cellular scale. Extensive efforts have been made to develop multifunctional neural probes, typically involving highly specialized fabrication processes. Here, we report a novel multifunctional neural probe platform realized by applying ultrathin nanoelectronic coating (NEC) on the surfaces of conventional microscale devices such as optical fibers and micropipettes. We fabricated the NECs by planar photolithography techniques using a substrate-less and multilayer design, which host arrays of individually addressed electrodes with an overall thickness below 1 µm. Guided by an analytic model and taking advantage of the surface tension, we precisely aligned and coated the NEC devices on the surfaces of these conventional microprobes and enabled electrical recording capabilities on par with the state-of-the-art neural electrodes. We further demonstrated optogenetic stimulation and controlled drug infusion with simultaneous, spatially resolved neural recording in a rodent model. This study provides a low-cost, versatile approach to construct multifunctional neural probes that can be applied to both fundamental and translational neuroscience.

MATLAB-based automated patch-clamp system for awake behaving mice.

Automation has been an important part of biomedical research for decades, and the use of automated and robotic systems is now standard for such tasks as DNA sequencing, microfluidics, and high-throughput screening. Recently, Kodandaramaiah and colleagues (Nat Methods 9: 585-587, 2012) demonstrated, using anesthetized animals, the feasibility of automating blind patch-clamp recordings in vivo. Blind patch is a good target for automation because it is a complex yet highly stereotyped process that revolves around analysis of a single signal (electrode impedance) and movement along a single axis. Here, we introduce an automated system for blind patch-clamp recordings from awake, head-fixed mice running on a wheel. In its design, we were guided by 3 requirements: easy-to-use and easy-to-modify software; seamless integration of behavioral equipment; and efficient use of time. The resulting system employs equipment that is standard for patch recording rigs, moderately priced, or simple to make. It is written entirely in MATLAB, a programming environment that has an enormous user base in the neuroscience community and many available resources for analysis and instrument control. Using this system, we obtained 19 whole cell patch recordings from neurons in the prefrontal cortex of awake mice, aged 8-9 wk. Successful recordings had series resistances that averaged 52 ± 4 MΩ and required 5.7 ± 0.6 attempts to obtain. These numbers are comparable with those of experienced electrophysiologists working manually, and this system, written in a simple and familiar language, will be useful to many cellular electrophysiologists who wish to study awake behaving mice.

Persistent activity in prefrontal cortex during trace eyelid conditioning: dissociating responses that reflect cerebellar output from those that do not.

Persistent neural activity, responses that outlast the stimuli that evoke them, plays an important role in neural computations and possibly in processes, such as working memory. Recent studies suggest that trace eyelid conditioning, which involves a temporal gap between the conditioned and unconditioned stimuli (the trace interval), requires persistent neural activity in a region of medial prefrontal cortex (mPFC). This persistent activity, which could be conveyed to cerebellum via a pathway through pons, may engage the cerebellum and allow for the expression of conditioned responses. Given the substantial reciprocity observed among many brain regions, it is essential to demonstrate that persistent responses in mPFC neurons are not simply a reflection of cerebellar feedback to the forebrain, leaving open the possibility that such responses could serve as input to the cerebellum. This concern is highlighted by studies showing that hippocampal learning-related activity is abolished by cerebellar inactivation. We inactivated the cerebellum while recording single-unit activity from the mPFC of rabbits trained with a forebrain-dependent trace eyelid conditioning procedure. We report that, whereas the responses of cells that show an onset of increased spike activity during the trace interval were abolished by cerebellar inactivation, persistent responses that begin during the conditioned stimulus and persisted into the trace interval were unaffected. Therefore, conditioned stimulus-evoked persistent responses remain the strongest candidate input pattern to support the cerebellar expression of learned responses.

Modification of persistent responses in medial prefrontal cortex during learning in trace eyeblink conditioning.

Persistent spiking in response to a discrete stimulus is considered to reflect the active maintenance of a memory for that stimulus until a behavioral response is made. This response pattern has been reported in learning paradigms that impose a temporal gap between stimulus presentation and behavioral response, including trace eyeblink conditioning. However, it is unknown whether persistent responses are acquired as a function of learning or simply represent an already existing category of response type. This fundamental question was addressed by recording single-unit activity in the medial prefrontal cortex (mPFC) of rabbits during the initial learning phase of trace eyeblink conditioning. Persistent responses to the tone conditioned stimulus were observed in the mPFC during the very first training sessions. Further analysis revealed that most cells with persistent responses showed this pattern during the very first training trial, before animals had experienced paired training. However, persistent cells showed reliable decreases in response magnitude over the first training session, which were not observed on the second day of training or for sessions in which learning criterion was met. This modification of response magnitude was specific to persistent responses and was not observed for cells showing phasic tone-evoked responses. The data suggest that persistent responses to discrete stimuli do not require learning but that the ongoing robustness of such responses over the course of training is modified as a result of experience. Putative mechanisms for this modification are discussed, including changes in cellular or network properties, neuromodulatory tone, and/or the synaptic efficacy of tone-associated inputs.

Association of a 40-Gene Expression Profile With Risk of Metastatic Disease Progression of Cutaneous Squamous Cell Carcinoma (cSCC) and Specification of Benefit of Adjuvant Radiation Therapy.

PURPOSE: Adjuvant radiation therapy (ART) for cutaneous squamous cell carcinoma (cSCC) is recommended based on a number of wide-ranging clinicopathologic features, which encompass a broad array of patients. The 40-gene expression profile (40-GEP) test classifies cSCC tumors into low (Class 1) or higher (Class 2A) or highest (Class 2B) risk of nodal and/or distant metastasis. This study's hypotheses are 1) local recurrence is associated with metastatic disease progression, and 2) 40-GEP, by identifying high risk for metastasis, could predict a metastasis-specific benefit from ART. METHODS: Samples were obtained from 920 patients (ART-untreated: 496 Class 1, 335 Class 2A, 33 Class 2B; ART-treated: 11 Class 1, 35 Class 2A, 10 Class 2B) who were matched on clinical risk factors and stratified by ART status, to create 49 matched patient strata. To control for the variety of characteristics and treatment selection bias, randomly sampled pairs of matched ART and non-ART patients comprising 10,000 resampled cohorts were each analyzed for 5-year metastasis-free survival and predicted time to metastatic event. RESULTS: Of 96 patients experiencing local recurrence, 56.3% experienced metastasis; of those experiencing both, 88.9% had local recurrence before (75.9%) or concurrently (13.0%) with metastasis. After matching for clinicopathological risk, median 5-year disease progression rates for resampled cohorts demonstrated approximately 50% improvement for Class 2B ART-treated as compared to ART-untreated cohorts. Class 2B ART-treated cohorts had a 5-fold delay in predicted time to metastatic event and deceleration of disease progression as compared to ART-untreated cohorts (Kolmogorov-Smirnov test, p<0.01); this was not observed for Class 1 or 2A patients (p>0.05 for each). No risk factor or staging system combined with ART status identified groups that would benefit from ART as well as 40-GEP. CONCLUSION: 40-GEP identifies patients at highest risk of nodal/distant metastasis who may derive greatest benefit from ART, as well as patients who may have clinical indications for ART but are at low risk of metastasis. Compared to current guidelines, 40-GEP could provide greater specificity concerning the benefit of ART in individual patients.

Understanding how primary care providers report discussing substance use with transgender and gender diverse patients.

OBJECTIVES: To explore how primary care providers report discussing substance use with transgender and gender diverse (TGD) adult patients within the context of discussing gender-affirming interventions. METHODS: Between March and April 2022, in-depth, semi-structured qualitative interviews were conducted with 15 primary care providers who care for TGD patients in the Northeastern US. Thematic analysis was used to analyze interview data and identify themes. RESULTS: Two primary themes emerged among providers: 1) placing a focus on harm reduction, emphasizing reducing negative consequences of substance use, and 2) using access to gender-affirming interventions as an incentive for patients to change their substance use patterns. CONCLUSIONS: Focusing on harm reduction can emphasize reducing potential adverse outcomes while working with TGD patients towards their gender-affirmation goals. Future research should explore varying approaches to how substance use is discussed with TGD patients, as well as the interpretation of gender-affirming clinical guidelines. PRACTICE IMPLICATIONS: Findings from this study indicate a need for enhancing provider knowledge around the appropriate application of gender-affirming care guidelines. Investing in training efforts to improve gender-affirming care is critical for encouraging approaches that prioritize harm reduction and do not unnecessarily prevent access to gender-affirming interventions.

The 31-Gene Expression Profile Test Outperforms AJCC in Stratifying Risk of Recurrence in Patients with Stage I Cutaneous Melanoma.

BACKGROUND: Patients with stage I cutaneous melanoma (CM) are considered at low risk for metastasis or melanoma specific death; however, because the majority of patients are diagnosed with stage I disease, they represent the largest number of melanoma deaths annually. The 31-gene expression profile (31-GEP) test has been prospectively validated to provide prognostic information independent of staging, classifying patients as low (Class 1A), intermediate (Class 1B/2A), or high (Class 2B) risk of poor outcomes. METHODS: Patients enrolled in previous studies of the 31-GEP were combined and evaluated for recurrence-free (RFS) and melanoma-specific survival (MSS) (n = 1261, "combined"). A second large, unselected real-world cohort (n = 5651) comprising clinically tested patients diagnosed 2013-2018 who were linked to outcomes data from the NCI Surveillance, Epidemiology, and End Results (SEER) Program registries was evaluated for MSS. RESULTS: Combined cohort Class 1A patients had significantly higher RFS than Class 1B/2A or Class 2B patients (97.3%, 88.6%, 77.3%, p < 0.001)-better risk stratification than AJCC8 stage IA (97.5%) versus IB (89.3%). The SEER cohort showed better MSS stratification by the 31-GEP (Class 1A = 98.0%, Class 1B/2A = 97.5%, Class 2B = 92.3%; p < 0.001) than by AJCC8 staging (stage IA = 97.6%, stage IB = 97.9%; p < 0.001). CONCLUSIONS: The 31-GEP test significantly improved patient risk stratification, independent of AJCC8 staging in patients with stage I CM. The 31-GEP provided greater separation between high- (Class 2B) and low-risk (Class 1A) groups than seen between AJCC stage IA and IB. These data support integrating the 31-GEP into clinical decision making for more risk-aligned management plans.

Improving systemic therapy selection for inflammatory skin diseases: A clinical need survey.

Background: Empirical decisions to select therapies for psoriasis (PSO) and atopic dermatitis (AD) can lead to delays in disease control and increased health care costs. However, routine molecular testing for AD and PSO are lacking. Objective: To examine (1) how clinicians choose systemic therapies for patients with PSO and AD without molecular testing and (2) to determine how often the current approach leads to patients switching medications. Methods: A 20-question survey designed to assess clinician strategies for systemic treatment of AD and PSO was made available to attendees of a national dermatology conference in 2022. Results: Clinicians participating in the survey (265/414, 64% response rate) ranked "reported efficacy" as the most important factor governing treatment choice (P < .001). However, 62% (165/265) of clinicians estimated that 2 or more systemic medications were typically required to achieve efficacy. Over 90% (239/265) of respondents would or would likely find a molecular test to guide therapeutic selection useful. Limitations: To facilitate ease of recall, questions focused on systemic therapies as a whole and not individual therapies. Conclusion: Clinicians want a molecular test to help determine the most efficacious drug for individual patients.