Feasibility and preliminary effectiveness of a cognitive-behavioral, family-centered partial hospitalization program for adolescents with anorexia nervosa and atypical anorexia nervosa at six- and twelve-month follow-up.

This study examined the feasibility and preliminary effectiveness of a cognitive-behavioral, family-centered partial hospitalization program (PHP) for adolescents with anorexia nervosa (AN) and atypical AN (AAN), and described the outpatient services received following discharge. Participants (N = 31) completed anthropometric and self-report assessments at admission, discharge, and six and twelve months after discharge from the PHP. Descriptive statistics explored markers of feasibility. Paired samples t-tests evaluated changes in weight and eating disorder (ED) symptomatology from admission to discharge, admission to six-month follow-up, and admission to twelve-month follow-up. Descriptive statistics and effect sizes compared symptoms at each timepoint between participants with AN and AAN. Results indicated that we were successful at recruiting greater than 50% of adolescents approached for this study. We collected follow-up data from more than 70% of participants at discharge, but did not meet this retention benchmark at six-month and twelve-month follow-ups. The entire sample demonstrated significant improvements in weight and ED symptomatology from admission to discharge, and generally maintained these improvements at six- and twelve-month follow-up. While descriptive statistics suggested that participants with AN and AAN received similar outpatient services following discharge from the PHP, those with AN experienced greater improvement in self-reported ED symptomatology than those with AAN at six- and twelve-month follow-up. These findings provide preliminary support for the efficacy of PHPs in treating adolescents with AN and AAN. Further research with larger sample sizes should investigate whether adolescents with AAN experience poorer outcomes than those with AN following discharge from a PHP.

Permanent section margin concordance after Mohs micrographic surgery with immunohistochemistry for invasive melanoma and melanoma in situ: A retrospective dual-center analysis.

BACKGROUND: Mohs micrographic surgery (MMS) for melanoma practices vary among dermatologic surgeons. The implementation of immunohistochemical staining in MMS for melanoma mitigates challenges associated with slide interpretation; however, the reliability of melanoma antigen recognized by T cells 1 (MART-1), the preferred immunostain for melanoma, has yet to be compared with permanent section pathology. OBJECTIVE: To assess concordance rates of MART-1 frozen sections and permanent section pathologic interpretation of melanoma treated with MMS. METHODS: A dual-center retrospective analysis was conducted to collect concordance and demographic data. Chi-square tests were performed for group comparisons of categorical variables. RESULTS: Of the 379 permanent sections sent, 367 were concordant with frozen section pathology for an overall concordance rate of 96.8%. Cases were stratified into indeterminately concordant and indisputably concordant. Twenty-two (6%) of cases were indeterminately concordant, whereas 345 (94.0%) of cases were indisputably concordant. LIMITATIONS: The concordance rate is derived from a comparison of adjacent tissue margins, an inevitable consequence of utilizing 2 techniques. CONCLUSION: To the author's knowledge, this study represents the largest investigation examining concordance rates of MART-1 frozen sections in Mohs for melanoma. High concordance disputes the ongoing need for additional permanent margins when using MART-1 in routine cases.

Preliminary effectiveness of a cognitive-behavioral, family-centered partial hospitalization program for children and adolescents with avoidant/restrictive food intake disorder.

OBJECTIVE: This study explored the preliminary effectiveness of a partial hospitalization program (PHP) for children/adolescents with avoidant/restrictive food intake disorder (ARFID). We evaluated how ARFID symptoms changed from admission to discharge, and collected follow-up data on symptoms and outpatient care following PHP discharge. METHOD: Twenty-two children/adolescents with ARFID (77.3% White, 63.6% female) completed measures assessing ARFID symptomatology at admission and discharge from a PHP for eating disorders. Six months and twelve months following their discharge, participants were contacted to complete study measures again and take part in an interview assessing follow-up care. RESULTS: Paired samples t tests indicated that participants demonstrated increases in weight and decreases in ARFID symptomatology from admission to discharge with medium to large effects. All participants reported receiving some form of outpatient treatment following discharge, with the type of outpatient services varying across participants. Data from the 86% of participants who completed the six-month follow-up and 50% who completed the twelve-month follow-up suggest that participants generally maintained treatment gains following PHP discharge. DISCUSSION: Participants experienced symptom improvements from admission to discharge and appeared to maintain these gains after discharge. These results provide preliminary evidence that PHPs are an effective treatment option for children and adolescents with ARFID. PUBLIC SIGNIFICANCE STATEMENT: This study provides preliminary evidence that intensive, evidence-based PHPs are effective in treating ARFID. Our findings suggest that children and adolescents with ARFID who receive flexible, cognitive-behavioral, family-centered treatment in a PHP for EDs experience improvements in weight and ARFID symptomatology from admission to discharge. Despite receiving variable and nonstandardized outpatient treatment, individuals with ARFID appear to maintain treatment gains 6 and 12 months after discharge in a PHP.

Postoperative Infections in Dermatologic Surgery: The Role of Wound Cultures.

BACKGROUND: Dermatologic surgery is associated with low postoperative infection rates, averaging from approximately 1% to 4.25%. Often, postoperative infections are treated empirically based on clinical diagnosis of infection, given it can take 48 to 72 hours for a wound culture to identify a pathogen. OBJECTIVE: We aimed to evaluate the efficacy of empiric antibiotics in dermatologic surgery postoperative infections and if wound cultures change postoperative antibiotic therapy. METHODS: A 7-center, retrospective analysis of postoperative infections, with culture data, in dermatologic surgery patients was performed. RESULTS: Of 91 cases of clinically diagnosed postoperative infection, 82.4% (n = 75) were successfully treated with empiric oral antibiotics (95% confidence interval [0.73-0.89], p < .0001). In 16 (17.6%) cases, initial empiric antibiotics were unsuccessful, and wound culture results altered antibiotic therapy in 9 cases (9.9%) with 6 (6.6%) of these cases requiring additional coverage for methicillin-resistant Staphylococcus aureus (MRSA). CONCLUSION: Empiric antibiotic treatment is usually appropriate for patients with postoperative surgical-site infections with wound cultures altering antibiotic management in a minority of cases. When empiric antibiotics fail, lack of MRSA coverage is usually the cause; therefore, providers should be aware of local MRSA prevalence and susceptibilities.

Interface dermatitis along Blaschko's lines.

Linear dermatoses are fascinating entities that likely reflect embryologically derived cutaneous mosaicism, even when they occur after childhood. Adult blaschkitis is a rare, relapsing inflammatory dermatitis that most often presents in middle age. It presents clinically as a pruritic eruption of linear papules, vesicles and plaques, and is most commonly found to have features of spongiotic dermatitis on pathology. However, the clinical and histopathologic presentation of lichen striatus in adults may be similar to those of adult blaschkitis. A case in which 'blaschkitis' was suspected clinically is presented, in which the biopsy showed non-characteristic microscopic features resembling erythema multiforme--a finding rarely reported in the literature to date. We present this case and a brief review of the most commonly acquired linear eruptions following Blaschko's lines with the goal of expanding the histopathologic findings that may be encountered in adult blaschkitis. Moreover, the clinical and histopathologic overlap between the entities of blaschkitis and lichen striatus is explored, acknowledging that these entities may exist on a clinicopathologic spectrum. In the diagnosis of linear eruptions, clinicopathologic correlation is important for arriving at an accurate final diagnosis.

Inhibition of Enhancer of Zeste Homolog 2 Induces Blast Differentiation, Impairs Engraftment and Prolongs Survival in Murine Models of Acute Myeloid Leukemia.

BACKGROUND: Acute myeloid leukemia (AML) is the malignant proliferation of immature myeloid cells characterized by a block in differentiation. As such, novel therapeutic strategies to promote the differentiation of immature myeloid cells have been successful in AML, although these agents are targeted to a specific mutation that is only present in a subset of AML patients. In the current study, we show that targeting the epigenetic modifier enhancer of zeste homolog 2 (EZH2) can induce the differentiation of immature blast cells into a more mature myeloid phenotype and promote survival in AML murine models. METHODS: The EZH2 inhibitor EPZ011989 (EPZ) was studied in AML cell lines, primary in AML cells and normal CD34+ stem cells. A pharmacodynamic assessment of H3K27me3; studies of differentiation, cell growth, and colony formation; and in vivo therapeutic studies including the influence on primary AML cell engraftment were also conducted. RESULTS: EPZ inhibited H3K27me3 in AML cell lines and primary AML samples in vitro. EZH2 inhibition reduced colony formation in multiple AML cell lines and primary AML samples, while exhibiting no effect on colony formation in normal CD34+ stem cells. In AML cells, EPZ promoted phenotypic evidence of differentiation. Finally, the pretreatment of primary AML cells with EPZ significantly delayed engraftment and prolonged the overall survival when engrafted into immunodeficient mice. CONCLUSIONS: Despite evidence that EZH2 silencing in MDS/MPN can promote AML pathogenesis, our data demonstrate that the therapeutic inhibition of EZH2 in established AML has the potential to improve survival.

Pyrimidine depletion enhances targeted and immune therapy combinations in acute myeloid leukemia.

Acute myeloid leukemia (AML) is a fatal disease characterized by the accumulation of undifferentiated myeloblasts, and agents that promote differentiation have been effective in this disease but are not curative. Dihydroorotate dehydrogenase inhibitors (DHODHi) have the ability to promote AML differentiation and target aberrant malignant myelopoiesis. We introduce HOSU-53, a DHODHi with significant monotherapy activity, which is further enhanced when combined with other standard-of-care therapeutics. We further discovered that DHODHi modulated surface expression of CD38 and CD47, prompting the evaluation of HOSU-53 combined with anti-CD38 and anti-CD47 therapies, where we identified a compelling curative potential in an aggressive AML model with CD47 targeting. Finally, we explored using plasma dihydroorotate (DHO) levels to monitor HOSU-53 safety and found that the level of DHO accumulation could predict HOSU-53 intolerability, suggesting the clinical use of plasma DHO to determine safe DHODHi doses. Collectively, our data support the clinical translation of HOSU-53 in AML, particularly to augment immune therapies. Potent DHODHi to date have been limited by their therapeutic index; however, we introduce pharmacodynamic monitoring to predict tolerability while preserving antitumor activity. We additionally suggest that DHODHi is effective at lower doses with select immune therapies, widening the therapeutic index.

Development of an Electronic Health Record-Based Clinical Decision Support Tool for Patients With Lynch Syndrome.

PURPOSE: To develop an electronic health record (EHR)-based clinical decision support (CDS) tool to promote guideline-recommended cancer risk management among patients with Lynch syndrome (LS), an inherited cancer syndrome that confers an increased risk of colorectal and other cancer types. MATERIALS AND METHODS: We conducted a cross-sectional study to determine the baseline prevalence and predictors of guideline-recommended colonic surveillance and annual genetics program visits among patients with LS. Multivariable log-binomial regressions estimated prevalence ratios (PRs) of cancer risk management adherence by baseline sociodemographic and clinical characteristics. These analyses provided rationale for the development of an EHR-based CDS tool to support patients and clinicians with LS-related endoscopic surveillance and annual genetics program visits. The CDS leverages an EHR platform linking discrete genetic data to LS Genomic Indicators, in turn driving downstream clinician- and patient-facing CDS. RESULTS: Among 323 patients with LS, cross-sectional adherence to colonic surveillance and annual genetics program visits was 69.3% and 55.4%, respectively. Patients with recent electronic patient portal use were more likely to be adherent to colonic surveillance (PR, 1.67; 95% CI, 1.11 to 2.52). Patients more recently diagnosed with LS were more likely to be adherent to annual genetics program visits (PR, 0.58; 95% CI, 0.44 to 0.76 for 2-4 years; PR, 0.62; 95% CI, 0.51 to 0.75 for ≥4 compared with <2 years). Our EHR-based CDS tool is now active for 421 patients with LS throughout our health system. CONCLUSION: We have successfully developed an EHR-based CDS tool to promote guideline-recommended cancer risk management among patients with LS.

The Impact of Virtual Interviewing During the COVID-19 Pandemic on the Residency Application Process: One Institution's Experience.

PURPOSE: To assess the impact of virtual interviewing during the COVID-19 pandemic on the residency application process and to compare applicant costs and time spent interviewing during the 2020-2021 application cycle with prior years. METHOD: Fourth-year medical students at the University of Kansas School of Medicine applying for first-year residency positions via the National Resident Matching Program Match completed an electronic 46-item survey after submitting their rank lists during each application cycle from 2015-2016 to 2020-2021. The authors used descriptive statistics and t tests to analyze and compare responses to demographics questions and questions regarding number of submitted applications, offered and completed interviews, ranked programs, costs, and time spent interviewing. They used thematic analysis to code respondents' narrative comments about the virtual interviewing experience. RESULTS: From 2015-2016 to 2020-2021, 994 (of 1,190; 83.5%) respondents completed the survey. From 2019-2020 to 2020-2021, the average total cost of applying to residency per applicant dropped by $3,566 (P < .001) and the average time spent interviewing dropped by 13.3 days (P < .001). At the same time, the average number of applications per applicant dropped by 3.4, and applicants completed the same number of interviews and ranked 2.3 fewer programs, none of which were statistically significant differences. Narrative comments from 113 (79%) respondents in 2020-2021 revealed 4 themes related to virtual interviewing: convenience of time and cost, positive aspects of the process, negative aspects of the process, and overall impressions of the program. CONCLUSIONS: Virtual interviewing during the 2020-2021 application cycle resulted in an approximately 80% reduction in cost for applicants and an approximately 50% decrease in time spent interviewing compared with previous years but was not associated with large increases in number of submitted applications, completed interviews, or ranked programs. Applicants generally perceived virtual interviewing as positive although they raised notable concerns.

Evaluation of serum calcium differences in hypertensive crises and control patients: A randomly matched case-control study.

The role of calcium in blood pressure has been widely studied among hypertensive patients; however, no study has explored the role of calcium in hypertensive crises. The primary objective of this study is to evaluate the differences in serum calcium levels between hypertensive crises patients and a 1:1 random matched controls (age-, sex-, race-, diabetes, and body mass index matched). This study is a single-center, retrospective, chart review, case-control study of patients with hypertensive crises (case group) and patients without hypertensive crises (control group). Patients were included in the case group if they were 18 years of age or older with hypertensive crises and have a documented calcium level. The control group patients were required to be 18 years of age or older, have a documented calcium level, and have no diagnosis of hypertensive crises. The primary outcome of the study was to compare the mean serum calcium in patients with hypertensive crises vs patients without hypertensive crises. Five hundred and sixty-six patients were included in the study: 283 patients in both the case group and control group. The primary outcome results showed that serum calcium concentration was not significantly different between the case group (8.99 ± 0.78 mg/dL) and control group (8.96 ± 0.75 mg/dL) (P = .606). This study found no significant difference in serum calcium levels in patients with hypertensive crises compared to a random matched control group. Larger observational or experimental studies may be useful to evaluate the effect of calcium on blood pressure in hypertensive crises.

Free Fatty Acids Rewire Cancer Metabolism in Obesity-Associated Breast Cancer via Estrogen Receptor and mTOR Signaling.

Obesity is a risk factor for postmenopausal estrogen receptor alpha (ERα)-positive (ER+) breast cancer. Molecular mechanisms underlying factors from plasma that contribute to this risk and how these mechanisms affect ERα signaling have yet to be elucidated. To identify such mechanisms, we performed whole metabolite and protein profiling in plasma samples from women at high risk for breast cancer, which led us to focus on factors that were differentially present in plasma of obese versus nonobese postmenopausal women. These studies, combined with in vitro assays, identified free fatty acids (FFA) as circulating plasma factors that correlated with increased proliferation and aggressiveness in ER+ breast cancer cells. FFAs activated both the ERα and mTOR pathways and rewired metabolism in breast cancer cells. Pathway preferential estrogen-1 (PaPE-1), which targets ERα and mTOR signaling, was able to block changes induced by FFA and was more effective in the presence of FFA. Collectively, these data suggest a role for obesity-associated gene and metabolic rewiring in providing new targetable vulnerabilities for ER+ breast cancer in postmenopausal women. Furthermore, they provide a basis for preclinical and clinical trials where the impact of agents that target ERα and mTOR signaling cross-talk would be tested to prevent ER+ breast cancers in obese postmenopausal women. SIGNIFICANCE: These findings show that obesity-associated changes in certain blood metabolites rewire metabolic programs in cancer cells, influence mammary epithelial cell tumorigenicity and aggressiveness, and increase breast cancer risk.

Skin cancer screening: recommendations for data-driven screening guidelines and a review of the US Preventive Services Task Force controversy.

Melanoma is usually apparent on the skin and readily detected by trained medical providers using a routine total body skin examination, yet this malignancy is responsible for the majority of skin cancer-related deaths. Currently, there is no national consensus on skin cancer screening in the USA, but dermatologists and primary care providers are routinely confronted with making the decision about when to recommend total body skin examinations and at what interval. The objectives of this paper are: to propose rational, risk-based, data-driven guidelines commensurate with the US Preventive Services Task Force screening guidelines for other disorders; to compare our proposed guidelines to recommendations made by other national and international organizations; and to review the US Preventive Services Task Force's 2016 Draft Recommendation Statement on skin cancer screening.

Playground Safety is Associated With Playground, Park, and Neighborhood Characteristics.

BACKGROUND: More than 200,000 children each year are treated at emergency departments for injuries occurring on playgrounds. Empirically derived data are needed to elucidate factors associated with playground safety and reduce injury rates. OBJECTIVE: Determine if neighborhood, park and playground characteristics are significantly associated with playground safety. METHODS: A 24-item report card developed by the National Program for Playground Safety was used to assess playground safety at 41 public parks in a small to midsized, Midwestern city. Trained assessors evaluated the parks and playgrounds in June/July and used a standardized method to count the numbers of users. Data from the 2010 U.S. Census were used to describe the neighborhoods surrounding the parks. RESULTS: The average safety score for all playgrounds was 77.4% which denotes acceptable safety levels. However, 17.1% of the playgrounds were potentially hazardous and in need of corrective measures. Playgrounds were safer in neighborhoods with more youth (< 18 years of age) and educated adults and in parks with better quality features. Playgrounds with fewer amenities were relatively less safe. CONCLUSIONS: Park safety levels need to be improved to reduce the risk of physical injuries. Future studies examining cause-effect associations between environmental features and playground safety are warranted.