Functional and Cutaneous Treatment Outcomes With Intravenous Immunoglobulin for Eosinophilic Fasciitis: A Retrospective Study.

BACKGROUND: Eosinophilic fasciitis (EF) is a rare subtype of deep morphea with an elevated risk of functional impairment. No treatment algorithm has been established for adults with EF refractory to traditional corticosteroid or immunomodulatory treatments. Research on cutaneous and functional outcomes of alternative therapies, such as intravenous immunoglobulin (IVIG), remains scarce.  Objective: To describe the functional and cutaneous outcomes associated with IVIG in adults with treatment-refractory EF at a tertiary referral center. METHODS: We performed a retrospective chart review of 18 consecutive patients with EF identified through a billing code search seen within the UCSF Department of Dermatology between 2015 and 2022.  Results: Seven patients (41.2%) underwent at least one course of intravenous immunoglobulins (IVIG) during the study period. Of 6 patients with available follow-up data, 5 patients (83.3%) achieved both sustained cutaneous and functional improvement. In the IVIG cohort, 1 patient (16.7%) achieved complete response with relapse, 4 (66.7%) were partial responders, and 1 (16.7%) was a non-responder who required treatment with mepolizumab. CONCLUSION: Adverse effects of IVIG included headaches in 1 patient (14.3%) and rash in 2 patients (28.6%). There were no reported veno-occlusive or thromboembolic events associated with IVIG.  J Drugs Dermatol. 2024;23(4):8017.    doi:10.36849/JDD.8017e.

Direct-to-Patient Mobile Teledermoscopy: Prospective Observational Study.

Direct-to-patient mobile teledermoscopy is a feasible and useful adjunct to smartphone imaging for monitoring patient-identified lesions of concern, achieving comparable diagnostic and management accuracy as in-office dermatology.

Implementation and analysis of a multifaceted intervention for alcohol use disorder from a single academic urban emergency department.

BACKGROUND: From 2006 to 2014, alcohol-related visits to the emergency department (ED) increased by 76% in the United States, highlighting the need for improved ED-driven interventions addressing alcohol use disorder (AUD). Naltrexone is an FDA-approved medication for AUD shown to decrease craving and self-administration of alcohol. While oral naltrexone and extended-release naltrexone have been long utilized in primary care and inpatient hospital settings, the use of naltrexone in the ED is limited. METHODS: This study implemented and analyzed a multifaceted intervention regarding ED naltrexone prescribing at a large safety net, academic, urban hospital. A baseline assessment of preintervention conditions and perspectives on naltrexone prescribing was conducted through a chart review and standardized interviews with ED providers, respectively. The interview results guided design of interventions that addressed identified barriers. These included provider education, prescribing aids, and zero-cost naltrexone tablets supplied by the ED pharmacy to patients upon discharge. RESULTS: Between September 1, 2019, and August 31, 2020, of 753 unique patients who had a primary diagnosis or chief complaint containing the word "alcohol," only five (0.66%) were prescribed naltrexone. ED providers identified lack of training regarding naltrexone, lack of a prescribing protocol, and limited patient and provider education materials as barriers to prescribing naltrexone. Following the intervention, among 278 eligible patients, 11 oral naltrexone prescriptions were written (3.96%) between April 13, 2021, and August 1, 2021. This represents a sixfold increase over the preintervention period. CONCLUSIONS: An intervention to increase ED oral naltrexone prescriptions for AUD was successfully implemented, addressing lack of provider education, lack of prescribing resources, and patient barriers to accessing prescribed medications. Longer-term follow-up is needed to assess the efficacy and sustainability of these interventions. Nevertheless, ED clinicians are well positioned to initiate naltrexone prescriptions for patients presenting with AUD.

Stricker Learning Span criterion validity: a remote self-administered multi-device compatible digital word list memory measure shows similar ability to differentiate amyloid and tau PET-defined biomarker groups as in-person Auditory Verbal Learning Test.

OBJECTIVE: The Stricker Learning Span (SLS) is a computer-adaptive digital word list memory test specifically designed for remote assessment and self-administration on a web-based multi-device platform (Mayo Test Drive). We aimed to establish criterion validity of the SLS by comparing its ability to differentiate biomarker-defined groups to the person-administered Rey's Auditory Verbal Learning Test (AVLT). METHOD: Participants (N = 353; mean age = 71, SD = 11; 93% cognitively unimpaired [CU]) completed the AVLT during an in-person visit, the SLS remotely (within 3 months) and had brain amyloid and tau PET scans available (within 3 years). Overlapping groups were formed for 1) those on the Alzheimer's disease (AD) continuum (amyloid PET positive, A+, n = 125) or not (A-, n = 228), and those with biological AD (amyloid and tau PET positive, A+T+, n = 55) vs no evidence of AD pathology (A-T-, n = 195). Analyses were repeated among CU participants only. RESULTS: The SLS and AVLT showed similar ability to differentiate biomarker-defined groups when comparing AUROCs (p's > .05). In logistic regression models, SLS contributed significantly to predicting biomarker group beyond age, education, and sex, including when limited to CU participants. Medium (A- vs A+) to large (A-T- vs A+T+) unadjusted effect sizes were observed for both SLS and AVLT. Learning and delay variables were similar in terms of ability to separate biomarker groups. CONCLUSIONS: Remotely administered SLS performed similarly to in-person-administered AVLT in its ability to separate biomarker-defined groups, providing evidence of criterion validity. Results suggest the SLS may be sensitive to detecting subtle objective cognitive decline in preclinical AD.

Climate Change and Pregnancy: Risks, Mitigation, Adaptation, and Resilience.

Importance: Climate change is affecting the earth, resulting in more extreme temperatures and weather, rising sea levels, more frequent natural disasters, and displacement of populations of plants and animals, including people and insects. These changes affect food and housing security, vector-borne illnesses, and access to clean air and water, all of which influence human health. Evidence and Results: There are a number of adverse health outcomes linked to heat, air pollution from wildfires, stress from natural disasters, and other elements of climate change. Pregnant people are especially vulnerable to the health harms resulting from climate change, namely, preterm birth, small for gestational age, hypertensive disorders of pregnancy, and other adverse reproductive health and birth outcomes. Strategies to minimize these harms include mitigation and adaptation. Conclusions and Relevance: Physicians are in a unique position to protect the health of pregnant persons and children by advocating for policy changes that address climate change and providing clinical recommendations for patients to protect themselves from the health impacts of climate hazards.

Clinical and therapeutic course in head variants of linear morphea in adults: a retrospective review.

Parry Romberg Syndrome (PRS) and en coup de sabre (ECDS) are head variants of linear morphea with functional and structural implications. This study describes the clinical course, autoimmune co-morbidities, complications, and treatment of adults with PRS/ECDS at a tertiary referral center. We retrospectively reviewed the records of all 34 adult patients with PRS/ECDS identified through billing code search and seen by dermatologists at our institution between 2015 and 2021. Eight patients (23.5%) had ECDS, 8 (23.5%) had PRS, and 18 (52.9%) had overlap. Twenty-six patients (76.5%) reported ocular, oral, and/or neurologic symptoms, and 8 (23.5%) had concomitant autoimmune/inflammatory conditions. Sixteen patients (47.1%) had a skin biopsy, and 25 (73.5%) had imaging. Forty-six MRIs were obtained, of which 6 (13.0%) reported intracranial findings and 25 (54.3%) reported disease-related connective tissue damage. Twenty-four patients (70.6%) underwent systemic treatment during their disease course per available clinical records. Seventeen patients (70.8%) had improved or stable disease upon treatment completion, with an average duration of 22.2 months. Ten patients (41.7%) reported recurrence of disease following the treatment course. To address changes to facial contour, 6 patients (17.6%) opted for procedural treatments. One patient (16.7%) experienced morphea reactivation following a filler injection performed off-immunosuppression. Compared to findings in children, our study suggests adults with PRS/ECDS are more likely to have oral and ocular complications but experience less severe neurologic symptoms. While systemic treatments appear beneficial in most adult patients with PRS/ECDS, disease may recur following discontinuation.

Disparity in Access to Oncology Precision Care: A Geospatial Analysis of Driving Distances to Genetic Counselors in the U.S.

In the US, the growing demand for precision medicine, particularly in oncology, continues to put pressure on the availability of genetic counselors to meet that demand. This is especially true in certain geographic locations due to the uneven distribution of genetic counselors throughout the US. To assess these disparities, access to genetic counselors of all specialties is explored by geography, cancer type, and social determinants of health. Geospatial technology was used to combine and analyze genetic counselor locations and cancer incidence at the county level across the US, with a particular focus on tumors associated with BRCA mutations including ovarian, pancreatic, prostate and breast. Access distributions were quantified, and associations with region, cancer type, and socioeconomic variables were investigated using correlational tests. Nationally, in 2020, there were 4,813 genetic counselors, or 1.49 genetic counselors per 100,000 people, varying between 0.17 to 5.7 per 100,000 at the state level. Seventy-one percent of U.S. residents live within a 30-minute drive-time to a genetic counselor. Drive-times, however, are not equally distributed across the country - while 82% of people in metropolitan areas are 30 minutes from a genetic counselor, only 6% of people in nonmetro areas live within 30 minutes' drive time. There are statistically significant differences in access across geographical regions, socioeconomics and cancer types. Access to genetic counselors for cancer patients differs across groups, including regional, socioeconomic, and cancer type. These findings highlight areas of the country that may benefit from increased genetic counseling provider supply, by increasing the number of genetic counselors in a region or by expanding the use of telegenetics a term used to describe virtual genetic counseling consults that occur via videoconference. Policy intervention to allow genetic counselors to bill for their services may be an effective route for increasing availability of genetic counselors' services However, genetic counselors in direct patient care settings also face other challenges such as salary, job satisfaction, job recognition, overwork/burnout, and appropriate administrative/clinical support, and addressing these issues should also be considered along with policy support. These results could support targeted policy reform and alternative service models to increase access to identified pockets of unmet need, such as telemedicine. Data and analysis are available to the public through an interactive dashboard.

11ß-Hydroxysteroid dehydrogenase type 1 shRNA ameliorates glucocorticoid-induced insulin resistance and lipolysis in mouse abdominal adipose tissue.

Long-term glucocorticoid exposure increases the risk for developing type 2 diabetes. Prereceptor activation of glucocorticoid availability in target tissue by 11ß-hydroxysteroid dehydrogenase type 1 (11ß-HSD1) coupled with hexose-6-phosphate dehydrogenase (H6PDH) is an important mediator of the metabolic syndrome. We explored whether the tissue-specific modulation of 11ß-HSD1 and H6PDH in adipose tissue mediates glucocorticoid-induced insulin resistance and lipolysis and analyzed the effects of 11ß-HSD1 inhibition on the key lipid metabolism genes and insulin-signaling cascade. We observed that corticosterone (CORT) treatment increased expression of 11ß-HSD1 and H6PDH and induced lipase HSL and ATGL with suppression of p-Thr(172) AMPK in adipose tissue of C57BL/6J mice. In contrast, CORT induced adipose insulin resistance, as reflected by a marked decrease in IR and IRS-1 gene expression with a reduction in p-Thr(308) Akt/PKB. Furthermore, 11ß-HSD1 shRNA attenuated CORT-induced 11ß-HSD1 and lipase expression and improved insulin sensitivity with a concomitant stimulation of pThr(308) Akt/PKB and p-Thr(172) AMPK within adipose tissue. Addition of CORT to 3T3-L1 adipocytes enhanced 11ß-HSD1 and H6PDH and impaired p-Thr(308) Akt/PKB, leading to lipolysis. Knockdown of 11ß-HSD1 by shRNA attenuated CORT-induced lipolysis and reversed CORT-mediated inhibition of pThr(172) AMPK, which was accompanied by a parallel improvement of insulin signaling response in these cells. These findings suggest that elevated adipose 11ß-HSD1 expression may contribute to glucocorticoid-induced insulin resistance and adipolysis.

Transgenic overexpression of hexose-6-phosphate dehydrogenase in adipose tissue causes local glucocorticoid amplification and lipolysis in male mice.

The prereceptor activation of glucocorticoid production in adipose tissue by NADPH-dependent 11ß-hydroxysteroid dehydrogenase type 1 (11ß-HSD1) has emerged as a potential mechanism in the pathogenesis of visceral obesity and metabolic syndrome. Hexose-6-phosphate dehydrogenase (H6PDH) is an endoplasmic reticulum lumen-resident enzyme that generates cofactor NADPH and thus mediates 11ß-HSD1 activity. To determine the role of adipose H6PDH in the prereceptor modulation of 11ß-HSD1 and metabolic phenotypes, we generated a transgenic (Tg) mouse model overexpressing H6PDH under the control of the enhancer-promoter region of the adipocyte fatty acid-binding protein (aP2) gene (aP2/H6PDH Tg mice). Transgenic aP2/H6PDH mice exhibited relatively high expression of H6PDH and elevated corticosterone production with induction of 11ß-HSD1 activity in adipose tissue. This increase in corticosterone production in aP2-H6PDH Tg mice resulted in mild abdominal fat accumulation with induction of C/EBP mRNA expression and slight weight gain. Transgenic aP2/H6PDH mice also exhibited fasting hyperglycemia and glucose intolerance with insulin resistance. In addition, the aP2/H6PDH Tg mice have elevated circulating free fatty acid levels with a concomitant increased adipose lipolytic action associated with elevated HSL mRNA and Ser(660) HSL phosphorylation within abdominal fat. These results suggest that increased H6PDH expression specifically in adipose tissue is sufficient to cause intra-adipose glucocorticoid production and adverse metabolic phenotypes. These findings suggest that the aP2/H6PDH Tg mice may provide a favorable model for studying the potential impact of H6PDH in the pathogenesis of human metabolic syndrome.