Dermatologic needs of transgender and gender diverse youth: A retrospective cohort study.

Several dermatologic concerns are known to disproportionally affect transgender and gender-diverse (TGD) adults, but little is known about dermatologic conditions in TGD youth. This study assesses the prevalence of acne, androgenic alopecia, scarring from gender-affirming procedures, and eczema in pediatric TGD patients seen at Boston Children's Hospital between April 2021 and April 2022. The results demonstrate that, for TGD youth, the studied dermatologic concerns are common, referral rates to dermatology are low, and acne is significantly associated with testosterone use. Future studies should examine additional dermatologic concerns and barriers to accessing dermatologic care for this historically underserved population.

Experiences of adult survivors of childhood cancer in a randomized cardiovascular health promotion trial: a qualitative report from the Childhood Cancer Survivor Study.

PURPOSE: To better understand preferences and attitudes that adult-aged survivors of childhood cancer have toward survivorship care plans (SCP) and related SCP-based counseling. METHODS: Semi-structured qualitative interviews were conducted with 20 survivors participating in the Childhood Cancer Survivor Study who were at increased risk for cardiovascular disease secondary to their original cancer treatment. All participants were part of a larger randomized clinical trial (NCT03104543) testing the efficacy of an SCP-based counseling intervention with goal-setting designed to improve control of cardiovascular risk factors (i.e., hypertension, dyslipidemia, diabetes). A primarily deductive thematic analysis methodology guided interpretation; coded interview segments were grouped into primary themes of facilitators, barriers, suggestions, and positive sentiments. RESULTS: Participants described benefits of the intervention including facilitation of accountability, goal-setting, and increased knowledge of their health. Many participants also noted improved knowledge of their cancer treatment and subsequent risks, and they were interested in sharing this information with their primary care provider. However, several participants were disappointed when they did not achieve their goals or felt that they had low motivation. Participants generally wanted increased flexibility in the intervention, whether in the duration, frequency, or method of delivery. CONCLUSIONS: The SCP-based intervention was generally well-received by those interviewed and appears promising for promoting goal-setting and accountability as part of an SCP-based intervention to improve control of cardiovascular risk factors. IMPLICATIONS FOR CANCER SURVIVORS: Many survivors are at risk for cardiovascular disease or other potentially modifiable effects of their treatment. SCP-based interventions may facilitate improved control of these late effects.

Underdiagnosis and Undertreatment of Modifiable Cardiovascular Risk Factors Among Survivors of Childhood Cancer.

Background Determine the prevalence and predictors associated with underdiagnosis and undertreatment of modifiable cardiovascular disease (CVD) risk factors (hypertension, dyslipidemia, glucose intolerance/diabetes) among adult survivors of childhood cancer at high risk of premature CVD. Methods and Results This was a cross-sectional study of adult-aged survivors of childhood cancer treated with anthracyclines or chest radiotherapy, recruited across 9 US metropolitan regions. Survivors completed questionnaires and in-home clinical assessments. The comparator group was a matched sample from the National Health and Nutrition Examination Survey. Multivariable logistic regression estimated the risk (odds ratios) of CVD risk factor underdiagnosis and undertreatment among survivors compared with the National Health and Nutrition Examination Survey. Survivors (n=571; median age, 37.7 years and 28.5 years from cancer diagnosis) were more likely to have a preexisting CVD risk factor than the National Health and Nutrition Examination Survey (n=345; P<0.05 for all factors). While rates of CVD risk factor underdiagnosis were similar (27.1% survivors versus 26.1% National Health and Nutrition Examination Survey; P=0.73), survivors were more likely undertreated (21.0% versus 13.9%, P=0.007; odds ratio, 1.8, 95% CI, 1.2-2.7). Among survivors, the most underdiagnosed and undertreated risk factors were hypertension (18.9%) and dyslipidemia (16.3%), respectively. Men and survivors who were overweight/obese were more likely to be underdiagnosed and undertreated. Those with multiple adverse lifestyle factors were also more likely undertreated (odds ratio, 2.2, 95% CI, 1.1-4.5). Greater health-related self-efficacy was associated with reduced undertreatment (odds ratio, 0.5; 95% CI, 0.3-0.8). Conclusions Greater awareness of among primary care providers and cardiologists, combined with improving self-efficacy among survivors, may mitigate the risk of underdiagnosed and undertreated CVD risk factors among adult-aged survivors of childhood cancer. Registration URL: https://www.clinicaltrials.gov; Unique identifier: NCT03104543.

Direct Activation of Human MLKL by a Select Repertoire of Inositol Phosphate Metabolites.

Necroptosis is an inflammatory form of programmed cell death executed through plasma membrane rupture by the pseudokinase mixed lineage kinase domain-like (MLKL). We previously showed that MLKL activation requires metabolites of the inositol phosphate (IP) pathway. Here we reveal that I(1,3,4,6)P4, I(1,3,4,5,6)P5, and IP6 promote membrane permeabilization by MLKL through directly binding the N-terminal executioner domain (NED) and dissociating its auto-inhibitory region. We show that IP6 and inositol pentakisphosphate 2-kinase (IPPK) are required for necroptosis as IPPK deletion ablated IP6 production and inhibited necroptosis. The NED auto-inhibitory region is more extensive than originally described and single amino acid substitutions along this region induce spontaneous necroptosis by MLKL. Activating IPs bind three sites with affinity of 100-600 µM to destabilize contacts between the auto-inhibitory region and NED, thereby promoting MLKL activation. We therefore uncover MLKL's activating switch in NED triggered by a select repertoire of IP metabolites.