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Background: Many vascular anomalies harbor postzygotic somatic variants in GNAQ and GNA11; however, the phenotype of specific G-protein variants has not been well described. We report the clinical characteristics of 17 patients with a GNA11 R183C variant., Methods: This case series is derived from a multinational cohort of vascular anomaly patients whose pathogenic mutations were identified using high-depth next generation sequencing. Data include vascular anomaly features, imaging reports, and extracutaneous manifestations of the GNA11 R183C variant., Results: We identified 17 subjects (median age 18 years [range 6-67]) with somatic GNA11 R183C variant. All patients had vascular lesions of the skin that presented as pink-to-red in children and deeper red in adults. Most lesions were large, poorly demarcated, and reticulated patches that were often bilaterally distributed. Nevus anemicus was observed in 53% (N = 9) and dermal melanocytosis in 13.3% (N = 2) of individuals. 82% (N = 14) of patients had limb growth discrepancies, and 1 patient had marked thoracic hypoplasia. 47% (N = 8) of patients had facial involvement, and 41% (N = 7) had forehead involvement. One patient experienced seizures due to right hemispheric leptomeningeal angiomatosis consistent with Sturge-Weber syndrome. Other findings included glaucoma (29%, N = 5) and psychomotor delay (29%, N = 5)., Conclusion: These findings contribute to our understanding of the clinical spectrum of GNA11 R183C capillary malformations (CMs); patients characteristically present with extensive, bilateral, poorly demarcated, pink-to-red CMs associated with nevus anemicus. Glaucoma and growth discrepancies (overgrowth or undergrowth) are common. Leptomeningeal angiomatosis and developmental delay can occur, appearing potentially less prevalent and severe than GNAQ-associated disease., (© 2024 The Author(s). Pediatric Dermatology published by Wiley Periodicals LLC.)

Background: Pediatric Mycosis fungoides (MF) management extrapolates from adult guidelines, despite differing clinical aspects. Recommendations are essential to address unique challenges in this distinct patient group., Objective: This project aims to derive consensus recommendations for pediatric MF management., Methods: Experts from pediatric dermatology, general dermatology, dermatopathology, and pediatric hematology-oncology (N = 83) were invited to contribute to consensus recommendations. The process involved 3 electronic Delphi rounds, concluding with a final consensus meeting using a modified Nominal Group Technique for unresolved items., Results: Consensus included more clinical severity measures than tumor-node-metastasis-blood staging: pruritus, functional or esthetic impairment (eg, palms, soles, genitalia), quality of life impact, and psychological aspects (eg, embarrassment, anxiety, depression), plus parental anxiety. Ten recommendations were made for managing early and advanced pediatric MF. Disagreement emerged in choosing therapies beyond stage I of the disease., Discussion: This multinational initiative aimed to standardize optimal pediatric MF management and successfully generated consensus recommendations. Additional work is needed for structured, prospective protocols in advanced-stage pediatric MF., Limitations: Lack of pediatric hematologists-oncologists and patients' representatives., Conclusion: Documentation of extended clinical severity and outcome measures is recommended. Addressing the need for structured protocols in advanced-stage pediatric MF and implementing systematic, prospective data collection is crucial., Competing Interests: Conflicts of interest None disclosed., (Copyright © 2024 American Academy of Dermatology, Inc. Published by Elsevier Inc. All rights reserved.)

Background: We observed many preterm infants with unexpectedly thick infantile hemangiomas (IH), a subtype known to be associated with an increased risk of scarring., Objective: To cf the clinical features of localized IH in preterm vs term infants., Methods: A retrospective study was conducted at 3 tertiary referral centers involving 830 consecutive patients with localized IH., Results: Preterm infants had a significantly higher incidence of superficial IH (75% in <33 weeks, 57% in 33 to <37 weeks, and 50% in term infants, P = .007). Overall, their IH had thicker superficial components (P < .001) and more stepped borders (P < .001). These features correlated with the degree of prematurity. The average chronological age at presentation to the specialist was 5.6 (SD = 6.2) months, with no difference observed in gestational age., Limitations: The retrospective design and use of nonstandardized clinical photographs. There may be biases introduced toward more severe IH types because the study sites were tertiary referral centers., Conclusions: Preterm infants have features of IH that have obvious implications for systemic therapies. Most of these infants were seen beyond the typical proliferative phase when irreversible skin changes may have already occurred., Competing Interests: Conflicts of interest Esteban Fernández Faith is a consultant for Novartis. Irene Lara-Corrales is a consultant for Sanofi GenzymeAvicanna, Ipsen, Novartis, Eli Lilly, and Abeona; has been a speaker for Sanofi Genzyme, Abbvie, and Eli Lilly; and received grants/research support from Abbvie, Clementia, Eli Lilly, Timer Pharma, Arcutis, EB Medical Research Foundation, EB Research Partnership, Physicians Services Incorporated Foundation, SkIN Canada, La Roche Posse, Sanofi Gemzyme, Regeneron, and Mayne Pharma. Elena Pope is an advisory board member for Abbvie, Sanofi Genzyme, Johnson&Johnson, Pfizer, Pierre Fabre, Boehringer-Ingelheim, Novartis, and Timber Pharma. Ilona J. Frieden is a consultant for Noble Pharmaceutical and Novartis and is on the Chair Data Safety Monitoring Board of Pfizer and the Advisory Board of Verrica. The other authors have no conflict of interest to disclose., (Copyright © 2024. Published by Elsevier Inc.)

Importance: Patients with recessive dystrophic epidermolysis bullosa (RDEB) experience neuropathic pain and itch. There is a lack of evidence on any treatment for these symptoms in patients with RDEB., Objectives: To test the efficacy of pregabalin in the treatment of neuropathic pain and itch in patients with RDEB., Design, Setting, and Participants: A randomized, double-blinded, crossover trial of oral pregabalin (50-300 mg/d) vs placebo was conducted at 2 sites, Toronto (Canada) and Santiago (Chile) from January 1, 2019, to December 31, 2020. Patients eligible to participate were diagnosed with RDEB, aged 8 to 40 years, not pregnant or lactating (if female), and had evidence of probable neuropathic pain and itching defined as distal thermal sensory loss (confirmed by thermal roller), score of 4 or greater on the Douleur Neuropathique 4 questionnaire (DN4), and score greater than 4 on the 10-point visual analog scale [VAS]). Patients with a clinically important or poorly controlled medical or psychiatric condition or pregabalin intolerance or allergy were excluded. Of 41 patients screened, 3 were not eligible and 28 declined enrollment. Data analyses were performed in 2021 through 2023., Intervention: Participants received both pregabalin and matched placebo (titrated to a maximum-tolerated dose of 300 mg/day) in a randomized sequence so that comparisons could be made within participants and between groups., Main Outcomes and Measures: Difference in the mean pain and itch scores between pregabalin and placebo treatment (measured using VAS) before and after intervention., Results: In all, 10 participants were randomized to 2 groups, 6 patients (mean [SD] age, 26.7 [8.1] years; 3 females [50%]) in group 1, and 4 patients (mean [SD] age, 26.5 [7.8] years, 2 females [50%]) in group 2. Group 1 received a sequence of pregabalin-placebo while group 2 received placebo-pregabalin. Pregabalin significantly reduced mean (SD) pain scores by 1.9 (1.5) points when controlling for sequence and treatment period vs baseline, while placebo had 0.1 (2.0) points of reduction. The effect of pregabalin was a mild but significant reduction in itch compared to baseline (mean [SD] points, 0.9 [2.2]), whereas the placebo produced no reduction (0.1 [2.5]). The mean pregabalin dose was generally well tolerated., Conclusions and Relevance: The results of this randomized crossover trial indicate that pregabalin significantly reduced pain and itch scores from baseline compared to placebo in patients with RDEB. This feasibility study provided preliminary data on the efficacy of pregabalin in managing pain and itch in RDEB and gathered essential data to inform the design of a larger cohort trial., Trial Registration: ClinicalTrials.gov Identifier: NCT03928093.

Background: Understanding opioid overdose risk perception may inform overdose prevention strategies., Methods: We used baseline data from a randomized overdose prevention trial, in San Francisco, CA, and Boston, MA, among people who used nonprescribed opioids, survived an overdose in the past 3 years, and had received naloxone. Participants were asked how likely they were to overdose in the next 4 months. We combined "extremely likely" and "likely" (higher risk perception) and "neutral," "unlikely," and "extremely unlikely" (lower risk perception). We performed bivariate analyses and separate multivariable logistic regression models of risk perception across (1) sociodemographic, (2) substance use, and (3) overdose risk behavior measures. Covariates were selected a priori or significant in bivariate analyses., Results: Among 268 participants, 88% reported at least 1 overdose risk behavior; however, only 21% reported higher risk perception. The adjusted odds ratio (AOR) of higher risk perception was 2.41 (95% confidence interval [CI]: 1.10-5.30) among those unhoused in the past 4 months, 2.06 (95% CI: 1.05-4.05) among those using opioids in a new place, and 5.61 (95% CI: 2.82-11.16) among those who had overdosed in the past 4 months. Living in Boston was associated with higher risk perception in all 3 models (AOR = 2.00-2.46, 95% CI: 1.04-4.88)., Conclusions: Despite prevalent risk behaviors, a minority of participants perceived themselves to be at higher risk of overdose. Nonetheless, some known risk factors for overdose were appropriately associated with risk perception. Fentanyl has been prevalent in Boston for longer than San Francisco, which may explain the higher risk perception there., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Aim: To describe the rates of stroke and craniocervical vasculopathy progression in children with posterior fossa malformations, hemangioma, arterial anomalies, coarctation of the aorta/cardiac defects, and eye abnormalities (PHACE) syndrome., Method: A single-center, retrospective natural history study of children with PHACE syndrome. Clinical and sequential neuroimaging data were reviewed to study the characteristics and progression of vasculopathy and calculate the rates of arterial ischemic stroke (AIS) and transient ischemic stroke (TIA). Vasculopathy progression was defined as worsening or new vascular findings on follow-up magnetic resonance angiography., Results: Thirty-four children with cerebrovascular abnormalities at the PHACE syndrome diagnosis were studied (age range = 2 to 18 years, 85% females). Median age at the initial diagnosis was 5.5 months (interquartile range = 1-52 months); median age at the last follow-up was 8 years 6 months (range = 2-18 years). Overall, 10 (29%) patients had radiological progression of their vasculopathy, with a cumulative progression-free rate of 73% (95% confidence interval [CI] = 0.57-0.89), and a cumulative TIA-free and AIS-free rate of 87% (95% CI = 0.745-0.99). Vasculopathy was continuously progressive in six patients (18%) at the last follow-up. Three patients (9%) had TIA and all had progressive vasculopathy. One patient had presumed perinatal AIS at the initial PHACE diagnosis, while no other patient experienced an AIS during the follow-up., Interpretation: In children with PHACE syndrome, craniocervical vasculopathy is non-progressive and asymptomatic in the majority of cases. The risk of ischemic stroke in these children is very low. Larger and prospective studies are necessary to confirm these findings., What This Paper Adds: Cerebrovascular vasculopathy in children with PHACE syndrome is predominantly non-progressive and asymptomatic. Cerebrovascular vasculopathy in children with PHACE syndrome is associated with a low risk of stroke during childhood. In children with progressive vasculopathy, neuroimaging progression was generally slow over the first years of life., (© 2024 The Authors. Developmental Medicine & Child Neurology published by John Wiley & Sons Ltd on behalf of Mac Keith Press.)

Importance: Detecting activity of morphea can be complex but is crucial for adequate treatment and outcome assessment. The Morphea Activity Measure (MAM) was recently validated, but its responsiveness to change in disease activity has not been studied., Objective: To evaluate the internal and external responsiveness of MAM to changes in disease activity in pediatric patients., Design, Setting, and Participants: This multicenter prospective, longitudinal prognostic study was performed from October 2021 to January 2023 at 4 pediatric referral centers in North America. Consecutive pediatric patients with morphea who were available for data collection at baseline and at a follow-up visit at least 3 months later were studied., Exposure: Patient demographics, clinical characteristics, and measurements of disease activity collected at baseline and the subsequent visit., Main Outcome and Measures: Responsiveness of MAM to disease activity according to the modified Localized Scleroderma Severity Index (mLoSSI), the Physician Global Assessment (PGA), and a patient and parent global assessment (PtGA) was analyzed using mean and percentage change, standardized effect size, and standardized response mean (SRM) from baseline to follow-up 3 or more months later. Differences between patients whose activity improved vs did not improve were evaluated using the Mann-Whitney U test. The correlation between percentage change in MAM score and mLoSSI, the PGA, and the PtGA was calculated using Spearman rank correlation., Results: A total of 43 patients (mean [SD] age at onset, 7.11 [3.18] years; 26 [60.5%] female) were included. The mean change and percentage change in MAM score were significantly larger in those whose disease activity improved by the PGA (mean: -18.75 [95% CI, -31.92 to -5.57] vs 2.73 [95% CI, -1.97 to 7.45]; percentage: -108.08% [95% CI, -155.21% to -60.95%] vs -24.11% [95% CI, -81.22% to 32.99%]) and by mLoSSI (mean: -24.15 [95% CI, -41.89 to -6.41] vs -1.30 [95% CI, -8.50 to 5.70]; percentage: -172.06% [95% CI, -263.68% to -80.45%] vs -21.57% [95% CI, -48.13% to 4.97%]) than in those whose activity did not change. The SRM of MAM was significantly different between groups for both measures; the responsiveness was large in those whose activity decreased by the PGA (-0.75 [95% CI, -1.29 to -0.22]) and mLoSSI (-0.97 [95% CI, -1.69 to -0.25]) and none to small in those whose activity did not change by the PGA (0.11 [95% CI, -0.08 to 0.30]) or mLoSSI (-0.05 [95% CI, -0.34 to 0.23]). Percentage change in MAM score correlated strongly and significantly with change in mLoSSI (ρ = 0.69; P < .001) and PGA (ρ = 0.65; P < .001), but there was no correlation with change in the PtGA (ρ = 0.26; P = .09)., Conclusions and Relevance: In this prognostic study, MAM was found to be internally and externally responsive to changes in disease activity. Further evaluation in mixed cohorts of all ages and specialties is needed.

Background: Atopic dermatitis (AD) is a chronic skin disease that affects 20% of children worldwide and is associated with low patient-reported quality of life (QoL). Crisaborole (CRIS) and tacrolimus 0.03% (TAC) are Food and Drug Administration (FDA)-approved topical treatments for mild to moderate AD with similar clinical efficacy. Utilization of patient-reported outcomes (PROs) may provide meaningful data on the impact of AD treatments on patients and caregivers. This study used PROs to monitor the impact of crisaborole (CRIS) and tacrolimus 0.03% (TAC) on children with mild/moderate atopic dermatitis (AD) and caregiver burden., Methods: This open-label study randomized 47 child-caregiver dyads to CRIS or TAC for 12 weeks. Disease severity, child quality of life (QoL), itch, pain interference, anxiety, depression, sleep, caregiver burden and caregiver QoL were assessed at baseline, 6 and 12 weeks., Results: A total of 36 dyads completed the study. Children (mean age = 8.0 ± 3.9 years) had mild baseline AD and were diverse by race (39% white; 36% Black) and gender (53% males). Caregivers were mostly female (78%; mean age = 37 ± 7.6 years). Both arms improved disease severity (Eczema Area and Severity Index) from baseline to 12 weeks (CRIS = -2.4 vs. TAC = -1.9). Within-arm analyses comparing baseline to 12 weeks revealed TAC, but not CRIS, improved all child and caregiver PROs except sleep (all p < 0.05)., Conclusions: Our results demonstrated that topical treatment for 12 weeks was more beneficial than 6 weeks, with TAC improving more PROs than CRIS. Future trials should implement PROs to fully understand the impact of AD treatments., (© 2024 European Academy of Dermatology and Venereology.)

Background: In contrast to clinical diagnosis via external examination, patient-related outcome measures (PROMs) allow access to patients' internal perceptions. In the case of epidermolysis bullosa (EB) - a rare disease characterized by a wide variety of symptoms and individual disease courses - it is important to integrate the patient's perspective into diagnostic processes. The Instrument for Scoring Clinical Outcomes of Research for EB (iscorEB) is an EB-specific measurement tool, combining a clinician score (iscorEB-c) and a patient questionnaire (iscorEB-p)., Objectives: The aim of this study is to establish the iscorEB-p as an independent PROM tool by exploring its psychometric properties., Methods: Sample-based psychometric testing and evaluation were performed on data collected via a multinational online cross-sectional study., Results: Data analysis was performed with n = 95 participants across all EB types. The reliability and internal consistency of the iscorEB-p was excellent (α = 0.90). Principal component analysis with a varimax rotation resulted in a two-factor solution, explaining 55.6% of the total variance, with the distinct factors 'everyday life functioning' and 'specific EB symptoms'. Convergent validity was shown by high correlations to the Satisfaction With Life Scale (r = -0.52, P < 0.001), the Quality of Life in Epidermolysis Bullosa questionnaire (r = 0.72, P < 0.001) and the Epidermolysis Bullosa Family Burden of Disease questionnaire (r = -0.73, P < 0.001)., Conclusions: The iscorEB-p is a reliable and valid instrument to assess patient-reported health status of people with EB., Competing Interests: Conflicts of interest The authors declare no conflicts of interest., (© The Author(s) 2024. Published by Oxford University Press on behalf of British Association of Dermatologists. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

Objective: Juvenile localized scleroderma (jLS) is a chronic autoimmune disease commonly associated with poor outcomes, including contractures, hemiatrophy, uveitis, and seizures. Despite improvements in treatment, >25% of patients with jLS have functional impairment. To improve patient evaluation, our workgroup developed the Localized scleroderma Total Severity Scale (LoTSS), an overall disease severity measure., Methods: LoTSS was developed as a weighted measure by a consensus process involving literature review, surveys, case vignettes, and multicriteria decision analysis. Feasibility was assessed in larger Childhood Arthritis and Rheumatology Research Alliance groups. Construct validity with physician assessment and inter-rater reliability was assessed using case vignettes. Additional evaluation was performed in a prospective patient cohort initiating treatment., Results: LoTSS severity items were organized into modules that reflect jLS disease patterns, with modules for skin, extracutaneous, and craniofacial manifestations. Construct validity of LoTSS was supported by a strong positive correlation with the Physician Global Assessment (PGA) of severity and damage and weak positive correlation with PGA-Activity, as expected. LoTSS was responsive, with a small effect size identified. Moderate-to-excellent inter-rater reliability was demonstrated. LoTSS was able to discriminate between patient subsets, with higher scores identified in those with greater disease burden and functional limitation., Conclusion: We developed a new LS measure for assessing cutaneous and extracutaneous severity and have shown it to be reliable, valid, and responsive. LoTSS is the first measure that assesses and scores all the major extracutaneous manifestations in LS. Our findings suggest LoTSS could aid assessment and management of patients and facilitate outcome evaluation in treatment studies., (© 2023 American College of Rheumatology.)

Objective: To characterize long-term outcomes of PHACE syndrome., Study Design: Multicenter study with cross-sectional interviews and chart review of individuals with definite PHACE syndrome ≥10 years of age. Data from charts were collected across multiple PHACE-related topics. Data not available in charts were collected from patients directly. Likert scales were used to assess the impact of specific findings. Patient-Reported Outcomes Measurement Information System (PROMIS) scales were used to assess quality of life domains., Results: A total of 104/153 (68%) individuals contacted participated in the study at a median of 14 years of age (range 10-77 years). There were infantile hemangioma (IH) residua in 94.1%. Approximately one-half had received laser treatment for residual IH, and the majority (89.5%) of participants were satisfied or very satisfied with the appearance. Neurocognitive manifestations were common including headaches/migraines (72.1%), participant-reported learning differences (45.1%), and need for individualized education plans (39.4%). Cerebrovascular arteriopathy was present in 91.3%, with progression identified in 20/68 (29.4%) of those with available follow-up imaging reports. Among these, 6/68 (8.8%) developed moyamoya vasculopathy or progressive stenoocclusion, leading to isolated circulation at or above the level of the circle of Willis. Despite the prevalence of cerebrovascular arteriopathy, the proportion of those with ischemic stroke was low (2/104; 1.9%). PROMIS global health scores were lower than population norms by at least 1 SD., Conclusions: PHACE syndrome is associated with long-term, mild to severe morbidities including IH residua, headaches, learning differences, and progressive arteriopathy. Primary and specialty follow-up care is critical for PHACE patients into adulthood., Competing Interests: Declaration of Competing Interest Supported by the 2021 Research Fellowship from the Pediatric Dermatology Research Alliance (PeDRA) as well as the 2021-2022 University of California San Francisco Yearlong Research Fellowship. The authors declare no conflicts of interest., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Pediatric melanoma presents with distinct clinical features compared to adult disease., Objective: Characterize risk factors and negative outcomes in pediatric melanoma., Methods: Multicenter retrospective study of patients under 20 years diagnosed with melanoma between January 1, 1995 and June 30, 2015 from 11 academic medical centers., Results: Melanoma was diagnosed in 317 patients, 73% of whom were diagnosed in adolescence (age ≥11). Spitzoid (31%) and superficial spreading (26%) subtypes were most common and 11% of cases arose from congenital nevi. Sentinel lymph node biopsy was performed in 68% of cases and positive in 46%. Fatality was observed in 7% of cases. Adolescent patients with melanoma were more likely to have family history of melanoma (P = .046) compared to controls., Limitations: Retrospective nature, cohort size, control selection, and potential referral bias., Conclusion: Pediatric melanoma has diverse clinical presentations. Better understanding of these cases and outcomes may facilitate improved risk stratification of pediatric melanoma., Competing Interests: Conflicts of interest SH reports honorarium from Elsevier and past consulting for Novan Pharmaceuticals., (Copyright © 2024. Published by Elsevier Inc.)

Objective: The prevalence and types of psychosocial complications of juvenile localized scleroderma (JLS), also known as morphea, an inflammatory and sclerosing disease involving the skin, fascia, muscle, and bone, are poorly understood., Methods: We performed a systematic review of literature published between 2000 and 2020 in PubMed, EMBASE, the Cochrane Skin Group Specialized Register, the Cochrane Central Register of Controlled Trials, and the Cumulative Index to Nursing and Allied Health Literature using the search terms "scleroderma, localized," "Morphea," "anxiety," "depression," "resilience," "social stigma," "quality of life," "mood," or "stress" and limited the search to pediatric patients and English language. Patient demographics, characteristics of JLS, and comorbidities were extracted. The outcomes included measures of health-related quality of life (HRQoL), psychosocial functioning, evaluation of self-perception, and the treatment burden of the study population. The protocol was registered with PROSPERO (CRD42021257124). Thematic synthesis generated descriptive analysis., Results: Thirteen studies fulfilled the inclusion criteria: three retrospective cohort studies, two prospective cohort studies, and eight cross-sectional studies. A total of 690 pediatric patients with JLS were included (n = 484 with linear scleroderma). Six studies used the Children's Dermatology Life Quality Index, reporting little to no effect on HRQoL. One study used the Health-Related Quality of Life in Children and Adolescents Questionnaire and did not find differences between children with JLS or atopic dermatitis and healthy controls. One study used a self-perception questionnaire that showed normal self-worth of patients with JLS. Two studies used focus groups, both reporting elevated levels of stress, decreased self-worth, "feeling different," and bullying/teasing in patients with JLS. These emotions were associated with skin symptoms (pain, itch, and tightness), physical limitations, and treatment burden., Conclusion: Overall, quantitative studies did not report a statistically significant impairment in HRQoL in JLS. However, qualitative studies (focus groups) reported significant psychosocial impacts related to JLS. There is a need to develop a JLS-specific tool for the HRQoL evaluation of this population., (© 2023 The Authors. Arthritis Care & Research published by Wiley Periodicals LLC on behalf of American College of Rheumatology.)

Background/objectives: Pediatric dermatitis and nonaccidental trauma (NAT) may have overlapping cutaneous presentations, posing a risk of misdiagnosis and subsequent emotional distress and further harm. Through a systematic literature review, we reviewed pediatric (<18 years old) patients investigated for both dermatitis and NAT., Methods: EMBASE and MEDLINE databases were searched. English publications with original data involving pediatric patients investigated for both dermatitis and NAT were included. Nonhuman studies and incomplete articles/conference abstracts were excluded. Data extracted included the first author, year of publication, study design, participant count, sex of the population, age of the population, cutaneous presentation, timing of presentation, Child Protective Services involvement, and case relation to dermatitis and NAT., Results: This review included 21 case reports or series encompassing 29 patients. Among 26 patients initially investigated as NAT (26.9% involving Child Protective Services), final diagnoses included irritant contact dermatitis (53.8%), phytophotodermatitis (30.8%), allergic contact dermatitis (7.7%), perianal infectious dermatitis (3.8%), and atopic dermatitis (3.8%). Three patients initially diagnosed with nontraumatic dermatitis were later found to be victims of physical (2/3; 66.7%) or sexual abuse (1/3; 33.3%)., Conclusions: Effective history-taking and physical examinations should encompass a history of laxative use, contact with furocoumarin-containing plants/fruit, parallel family/peer cutaneous presentations, caregiver involvement, financial burden, patient discomfort, birthmark assessment, and lesions aligning with diaper borders or toilet seats. Limitations of this review include potential underreporting and the inclusion of low-quality study designs and evidence., (© 2024 Wiley Periodicals LLC.)

Introduction: Pharmacists provide a spectrum of services and comprehensive medication management for patients with substance use disorders (SUDs) with many providing timely and increased access to care for patients. Prior studies have evaluated other healthcare professionals' attitudes, knowledge and practice in regard to SUD treatment and harm reduction services. However, no reviews to date summarise the available literature on the attitudes, knowledge and practice in regard to SUD treatment and harm reduction services from the pharmacist perspective. This scoping review aims to systematically map the extent, range and nature of available evidence and identify and describe gaps in knowledge, practice and attitudes towards SUD treatment among pharmacists with the goal of providing information for meaningful integration of pharmacists into SUD care., Methods and Analysis: We will use the framework proposed by Arksey and O'Malley (2005) updated with recommendations by Levac et al (2010) and the Joanna Briggs Institute (2020). The protocol is registered via Open Science Framework (https://osf.io/92dek). We will search for peer-reviewed literature containing empirical evidence investigating SUD treatment or harm reduction with outcomes pertaining to the knowledge, practice or attitudes of pharmacists. Findings will be guided and assessed by research objectives and summarised using descriptive statistics and thematically for quantitative and qualitative findings, respectively. This review will be conducted and reported in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses for Scoping Reviews., Ethics and Dissemination: Our findings will provide crucial information and support for future interventions and programmes which aim to meaningfully integrate pharmacists into SUD care. We will disseminate findings at conferences and publish in a peer-reviewed journal. In addition, we will integrate feedback on search strategy, data extraction and our dissemination approach from multidisciplinary collaborators including those within our team's institution and outside experts with clinical or administrative knowledge in SUD care., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

PACS1 syndrome is a neurodevelopmental disorder characterized by intellectual disability and distinct craniofacial abnormalities resulting from a de novo p.R203W variant in phosphofurin acidic cluster sorting protein 1 (PACS1). PACS1 is known to have functions in the endosomal pathway and nucleus, but how the p.R203W variant affects developing neurons is not fully understood. Here we differentiated stem cells towards neuronal models including cortical organoids to investigate the impact of the PACS1 syndrome-causing variant on neurodevelopment. While few deleterious effects were detected in PACS1 (+/R203W) neural precursors, mature PACS1 (+/R203W) glutamatergic neurons exhibited impaired expression of genes involved in synaptic signaling processes. Subsequent characterization of neural activity using calcium imaging and multielectrode arrays revealed the p.R203W PACS1 variant leads to a prolonged neuronal network burst duration mediated by an increased interspike interval. These findings demonstrate the impact of the PACS1 p.R203W variant on developing human neural tissue and uncover putative electrophysiological underpinnings of disease., (© 2024. The Author(s).)

Background/objective: Stiff skin syndrome (SSS) is a rare disorder characterized by "rock hard" indurated skin affecting different body parts. The localized variant poses a diagnostic challenge, as it is frequently mistaken for other inflammatory connective tissue disorders. The aim of this study is to provide insightful clinical, radiologic and diagnostic data that might prove useful for the evaluation, management and treatment of pediatric patients with segmental SS., Methods: This single-center cohort study included patients ≤18 years diagnosed with localized SSS from 1988 to 2021 in a quaternary pediatric healthcare center in Toronto, Canada. Data included demographics, clinical, histopathologic and radiologic features, treatments, and clinical course. Data were summarized with descriptive statistics (mean, standard deviation, medians, interquartile ranges [IQRs]) and frequencies., Results: A total of 11 patients were included. The sclerotic changes were measured clinically and radiologically, by a total of 16 imaging studies: 13 magnetic resonance imaging (MRI) and 3 ultrasound. MRI readings showed abnormal high signal intensity of the affected tissue correlating with the anatomical site of involvement in all cases, specifically, in the shoulder/pelvic girdle with limb extension. Shear wave ultrasound elastography (SWE) demonstrated higher values within the dermis compared to the control site., Conclusion: The presence of segmental sclerotic changes that affects the pelvic/shoulder girdle with extension to the extremities, in the absence of inflammation on biopsy and abnormal signaling intensity on imaging is suggestive of SSS. Skin SWE is a feasible, noninvasive, and objective instrument to evaluate and monitor sclerotic changes overtime, it could be potentially extrapolated to other pediatric skin sclerotic conditions., (© 2023 Wiley Periodicals LLC.)

Improving nutrition security in sub-Saharan Africa under increasing climate risks and population growth requires a strong and contextualized evidence base. Yet, to date, few studies have assessed climate-smart agriculture and nutrition security simultaneously. Here we use an integrated assessment framework (iFEED) to explore stakeholder-driven scenarios of food system transformation towards climate-smart nutrition security in Malawi, South Africa, Tanzania and Zambia. iFEED translates climate-food-emissions modelling into policy-relevant information using model output implication statements. Results show that diversifying agricultural production towards more micronutrient-rich foods is necessary to achieve an adequate population-level nutrient supply by mid-century. Agricultural areas must expand unless unprecedented rapid yield improvements are achieved. While these transformations are challenging to accomplish and often associated with increased greenhouse gas emissions, the alternative for a nutrition-secure future is to rely increasingly on imports, which would outsource emissions and be economically and politically challenging given the large import increases required., (© 2024. The Author(s).)