Extensive blaschkoid hypopigmentation in a girl with MED12-related disorder.

MED12-related disorders represent a spectrum of rare neurodevelopmental disorders causing intellectual disability, dysmorphic features, and other systemic abnormalities. We report a case of a 21-month-old girl with extensive hypopigmentation following Blaschko lines attributed to underlying MED12-related disorder.

Actions of ß-apo-carotenoids in differentiating cells: differential effects in P19 cells and 3T3-L1 adipocytes.

ß-Apo-carotenoids, including ß-apo-13-carotenone and ß-apo-14'-carotenal, are potent retinoic acid receptor (RAR) antagonists in transactivation assays. We asked how these influence RAR-dependent processes in living cells. Initially, we explored the effects of ß-apo-13-carotenone and ß-apo-14'-carotenal on P19 cells, a mouse embryonal carcinoma cell line that differentiates into neurons when treated with all-trans-retinoic acid. Treatment of P19 cells with either compound failed to block all-trans-retinoic acid induced differentiation. Liquid chromatography tandem mass spectrometry studies, however, established that neither of these ß-apo-carotenoids accumulates in P19 cells. All-trans-retinoic acid accumulated to high levels in P19 cells. This suggests that the uptake and metabolism of ß-apo-carotenoids by some cells does not involve the same processes used for retinoids and that these may be cell type specific. We also investigated the effects of two ß-apo-carotenoids on 3T3-L1 adipocyte marker gene expression during adipocyte differentiation. Treatment of 3T3-L1 adipocytes with either ß-apo-13-carotenone or ß-apo-10'-carotenoic acid, which lacks RAR antagonist activity, stimulated adipocyte marker gene expression. Neither blocked the inhibitory effects of a relatively large dose of exogenous all-trans-retinoic acid on adipocyte differentiation. Our data suggest that in addition to acting as transcriptional antagonists, some ß-apo-carotenoids act through other mechanisms to influence 3T3-L1 adipocyte differentiation.

A facile synthesis of dynamic, shape-changing polymer particles.

We herein report a new facile strategy to ellipsoidal block copolymer nanoparticles that exhibit a pH-triggered anistropic swelling profile. In a first step, elongated particles with an axially stacked lamellae structure are selectively prepared by utilizing functional surfactants to control the phase separation of symmetric polystyrene-b-poly(2-vinylpyridine) (PS-b-P2VP) in dispersed droplets. In a second step, the dynamic shape change is realized by cross-linking the P2VP domains, thereby connecting glassy PS discs with pH-sensitive hydrogel actuators.

Clinical analysis of myelin oligodendrocyte glycoprotein antibody-associated disease in a diverse cohort of children: A single-center observational study.

BACKGROUND: Prognostic markers for relapse and neurological disability following the first clinical event in children with myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD) remain lacking. We investigated the clinical profiles and early prognostic factors associated with relapsing disease or impaired functional outcome in a large single-center cohort of pediatric MOGAD. METHODS: We retrospectively analyzed the clinical and paraclinical data and treatment outcomes of children with MOGAD seen at Children's Health in Dallas, Texas from 2009 to 2022. Univariate analyses were used to evaluate factors from initial event associated with relapsing disease course and impaired functional outcome (modified Rankin scale [mRS] >1) at final follow-up. RESULTS: Our cohort comprised of 87 children of diverse race/ethnicity. Presentation with acute disseminated encephalomyelitis (ADEM) was more frequent in children aged ≤8 years and Caucasian background, whereas presentation with optic neuritis was more common in children aged >8 years and other race/ethnicity. 44.3 % (27/61) had relapsing disease course, of whom 48.0 % had multiple relapses. 30.3 % (23/76) had final mRS >1. Children with abnormal electroencephalogram had reduced relapse risk. Children with ADEM presentation, severe disease, low MOG-IgG titer, and central and systemic inflammation (represented by cerebrospinal fluid pleocytosis and serum leukocytosis, respectively) at onset had higher likelihood of final mRS >1. CONCLUSION: Abnormal electroencephalogram at the first event was associated with reduced relapse risk while disease severity and peripheral inflammation significantly contributed to final neurological disability. Further studies are needed to validate these findings as early risk factors for disability and relapse and to identify optimal treatment strategies.

Dermoscopy Differential Diagnosis Explorer (D3X) Ontology to Aggregate and Link Dermoscopic Patterns to Differential Diagnoses: Development and Usability Study.

BACKGROUND: Dermoscopy is a growing field that uses microscopy to allow dermatologists and primary care physicians to identify skin lesions. For a given skin lesion, a wide variety of differential diagnoses exist, which may be challenging for inexperienced users to name and understand. OBJECTIVE: In this study, we describe the creation of the dermoscopy differential diagnosis explorer (D3X), an ontology linking dermoscopic patterns to differential diagnoses. METHODS: Existing ontologies that were incorporated into D3X include the elements of visuals ontology and dermoscopy elements of visuals ontology, which connect visual features to dermoscopic patterns. A list of differential diagnoses for each pattern was generated from the literature and in consultation with domain experts. Open-source images were incorporated from DermNet, Dermoscopedia, and open-access research papers. RESULTS: D3X was encoded in the OWL 2 web ontology language and includes 3041 logical axioms, 1519 classes, 103 object properties, and 20 data properties. We compared D3X with publicly available ontologies in the dermatology domain using a semiotic theory-driven metric to measure the innate qualities of D3X with others. The results indicate that D3X is adequately comparable with other ontologies of the dermatology domain. CONCLUSIONS: The D3X ontology is a resource that can link and integrate dermoscopic differential diagnoses and supplementary information with existing ontology-based resources. Future directions include developing a web application based on D3X for dermoscopy education and clinical practice.

Subclinical optic neuritis in pediatric myelin oligodendrocyte glycoprotein antibody-associated disease.

BACKGROUND AND OBJECTIVES: The clinical spectrum of myelin oligodendrocyte glycoprotein (MOG) antibody-associated disease (MOGAD) is heterogenous and has evolved over time since the commercial availability of the anti-MOG antibody assay. Subclinical disease activity has been previously reported in the visual pathway, but prevalence data remains limited. We investigated subclinical optic neuritis (ON) based on changes on retinal nerve fiber layer (RNFL) thickness on optic coherence tomography (OCT) in pediatric patients who tested positive for the anti-MOG antibody. METHODS: In this retrospective, single-center cohort study, we examined children with MOGAD with at least one complete assessment of the anterior visual pathway. Subclinical ON was defined by structural visual system disease in the absence of a subjective complaint of vision loss, pain (particularly with eye movement), or color desaturation. RESULTS: Records were reviewed from 85 children with MOGAD, 67 of whom (78.8%) had complete records for review. Eleven children (16.4%) had subclinical ON on OCT. Ten had significant reductions in RNFL, of which one had two distinct episodes of decreased RNFL, and one had significant elevations in RNFL. Of the eleven children with subclinical ON, six (54.5%) had a relapsing disease course. We also highlighted the clinical course of three children with subclinical ON detected on longitudinal OCT, including two who had subclinical ON outside of clinical relapses. CONCLUSION: Children with MOGAD can have subclinical ON events that can manifest as significant reductions or elevations in RNFL on OCT. OCT should be used routinely in the management and monitoring of MOGAD patients.

Factors Associated With Dermatologic Follow-up vs Emergency Department Return in Patients With Hidradenitis Suppurativa After an Initial Emergency Department Visit.

Importance: Emergency department (ED) visitation is common for the treatment of hidradenitis suppurativa (HS), whereas dermatology outpatient care is low. The reasons underlying this differential follow-up have not been elucidated. Objective: To assess the interventions and patient factors associated with ED return following an initial ED visit for HS. Design, Setting, and Participants: This retrospective cohort study used data from the IBM® MarketScan® Commercial and Multi-State Medicaid databases (trademark symbols retained per database owner requirement). An HS cohort was formed from patients who had 2 or more claims for HS during the study period of 2010 to 2019 and with at least 1 ED visit for their HS or a defined proxy. Data were analyzed from November 2021 to May 2022. Exposures: Factors analyzed included those associated with the ED visit and patient characteristics. Main Outcomes and Measures: Primary outcomes were return to the ED or dermatology outpatient follow-up for HS or related proxy within 30 or 180 days of index ED visit. Results: This retrospective cohort study included 20 269 patients with HS (median [IQR] age, 32 [25-41] years; 16 804 [82.9%] female patients), of which 7455 (36.8%) had commercial insurance and 12 814 (63.2%) had Medicaid. A total of 9737 (48.0%) patients had incision and drainage performed at the index ED visit, 14 725 (72.6%) received an oral antibiotic prescription, and 9913 (48.9%) received an opioid medication prescription. A total of 3484 (17.2%) patients had at least 1 return ED visit for HS or proxy within 30 days, in contrast with 483 (2.4%) who had a dermatology visit (P < .001). Likewise, 6893 (34.0%) patients had a return ED visit for HS or proxy within 180 days, as opposed to 1374 (6.8%) with a dermatology visit (P < .001). Patients with Medicaid and patients who had an opioid prescribed were more likely to return to the ED for treatment of their disease (odds ratio [OR], 1.48; 95% CI, 1.38-1.58; and OR, 1.48; 95% CI, 1.39-1.58, respectively, within 180 days) and, conversely, less likely to have dermatology follow-up (OR, 0.16; 95% CI, 0.14-0.18; and OR, 0.81; 95% CI, 0.71-0.91, respectively, within 180 days). Conclusions and Relevance: This cohort study suggests that many patients with HS frequent the ED for their disease but are not subsequently seen in the dermatology clinic for ongoing care. The findings in this study raise the opportunity for cross-specialty interventions that could be implemented to better connect patients with HS to longitudinal care.

Assessment and Management of Acute Disseminated Encephalomyelitis (ADEM) in the Pediatric Patient.

Acute disseminated encephalomyelitis (ADEM) is an inflammatory demyelinating disease of the central nervous system that typically presents in childhood and is associated with encephalopathy and multifocal brain lesions. Although ADEM is thought to be a post-infectious disorder, the etiology is still poorly understood. ADEM is often a monophasic disorder, in contrast to other demyelinating disorders such as multiple sclerosis and neuromyelitis optica spectrum disorder. With increasing awareness, understanding, and testing for myelin oligodendrocyte glycoprotein antibodies, this disease is now known to be a cause of pediatric ADEM and also has the potential to be relapsing. Diagnostic evaluation for ADEM involves neuroimaging and laboratory studies to exclude potential infectious, inflammatory, neoplastic, and genetic mimics of ADEM. Acute treatment modalities include high-dose intravenous corticosteroids, therapeutic plasma exchange, and intravenous immunoglobulin. Long-term outcomes for ADEM are generally favorable, but some children have significant morbidity related to the severity of acute illness and/or manifest ongoing neurocognitive sequelae. Further research related to the optimal management of pediatric ADEM and its impact on prognosis is needed. This review summarizes the current knowledge of the pathogenesis, epidemiology, clinical features, diagnostic evaluation, treatment approaches, and outcomes in pediatric ADEM.

Clinical Features, Treatment Strategies, and Outcomes in Hospitalized Children With Immune-Mediated Encephalopathies.

BACKGROUND: Autoimmune encephalitis (AE) and acute disseminated encephalomyelitis (ADEM) are immune-mediated brain conditions that can cause substantial neurological sequalae. Data describing the clinical characteristics, treatments, and neurological outcomes for these conditions are needed. METHODS: This is a single-center retrospective review of children diagnosed with AE or ADEM over a nine-year period with discharge outcomes measured by the Modified Rankin Score. RESULTS: Seventy-five patients (23 with ADEM and 52 with AE) were identified. Patients with ADEM had a higher percentage of abnormal magnetic resonance imaging findings (100% vs 60.8%; P < 0.001) and a shorter time from symptom onset to diagnosis (6 vs 14 days; P = 0.024). Oligoclonal bands and serum and cerebrospinal fluid inflammatory indices were higher in patients with AE. Nearly all patients received corticosteroids followed by plasmapheresis or intravenous immunoglobulin, and treatment strategies did not differ significantly between groups. Second-line immune therapies were commonly used in patients with AE. Finally, patients with AE had trends toward longer hospital lengths of stay (21 vs 13 days) and a higher percentage of neurological disability at hospital discharge (59.6% vs 34.8%). CONCLUSIONS: Although patients with ADEM and AE may have similar presenting symptoms, we found significant differences in the frequency of imaging findings, symptom duration, and laboratory and cerebrospinal fluid profiles, which can assist in distinguishing between the diagnoses. Patients in both groups were treated with a combination of immunomodulating therapies, and neurological disability was common at hospital discharge.

Dermatologic Conditions of the Early Post-Transplant Period in Hematopoietic Stem Cell Transplant Recipients.

Hematopoietic stem cell transplants (HSCTs) are used to treat a variety of conditions, including hematologic malignancies, bone marrow failure syndromes, and immunodeficiencies. Over 60,000 HSCTs are performed annually worldwide, and the numbers continue to increase. Indeed, as new conditioning regimens develop, more and more individuals, including those of older age, will be eligible for transplants. Nevertheless, although HSCTs are clearly a life-saving and necessary treatment for thousands of patients per year, there is still substantial morbidity and mortality associated with the procedure. Of note, skin eruptions in the post-HSCT period are frequent and often significantly reduce quality of life in recipients. Moreover, these cutaneous findings sometimes herald an underlying systemic condition, presenting possible opportunities for timelier intervention. Dermatologists therefore play a vital role in distinguishing life-threatening conditions from benign issues and prompting recognition of critical complications earlier in their course. This article aims to review the major dermatologic conditions occurring in the early post-HSCT period.

Association of Leukemia Cutis With Survival in Acute Myeloid Leukemia.

Importance: Leukemia cutis (LC) is an important yet understudied extramedullary manifestation of leukemia. Previous reports have suggested poor prognosis for patients with LC, but these reports have largely consisted of descriptive studies with a limited number of patients. Objectives: To identify patient factors associated with LC and characterize the association of LC with the course of acute myeloid leukemia (AML). Design, Setting, and Participants: This retrospective, matched-cohort study included 1683 patients with AML diagnosed from January 1, 2005, to April 1, 2017, with and without biopsy-proven LC seen at a single-center, tertiary care hospital in St Louis, Missouri. To specifically evaluate differences in survival, propensity scoring was used to match patients with AML with LC to patients with AML without LC off the logit of propensity score based on age, race/ethnicity, sex, and leukemia type. Kaplan-Meier methods were used to compare cumulative probability survival. Matched survival analysis was performed with extended Cox regression to determine factors associated with leukemia-specific and overall survival. Main Outcomes and Measures: Leukemia-specific survival and overall survival. Results: A total of 1683 patients were reviewed, including 78 patients with biopsy-proven LC of the AML type and 1605 patients with AML without LC. A total of 62 of the patients with AML and LC (mean [SD] age, 58.2 [11.7] years; 33 [53.2%] male) were matched in a 1:3 ratio to 186 patients with AML without LC (mean [SD] age, 58.2 [13.5] years; 103 [55.4%] male). The 5-year survival among the 62 patients with AML with LC was 8.6%, shorter than the 28.3% among the 186 matched patients with AML without LC. Matched survival analysis revealed that patients with AML and LC compared with those without LC had hazard ratios of 2.06 (95% CI, 1.26-3.38; P = .004) for leukemia-specific death and of 1.66 (95% CI, 1.06-2.60; P = .03) for all-cause death. In addition, matched patients with LC had greater odds of extramedullary organ burden (odds ratio, 3.48; 95% CI, 1.72-7.05; P < .001). Conclusions and Relevance: The results suggest that the presentation of LC in patients with AML is associated with decreased overall survival and leukemia-specific survival. Patients with AML presenting with LC may require more intensive treatment and monitoring of their leukemic disease.

Pediatric Multiple Sclerosis: From Recognition to Practical Clinical Management.

Pediatric-onset multiple sclerosis (MS) is a rare but increasingly recognized condition that both parallels and diverges from adult-onset MS. Exposure to key risk determinants for MS disease pathogenesis may occur during childhood. The diagnosis of pediatric MS can be challenging due to potential for atypical presentations and a broad differential diagnosis. MS disease-modifying therapies have not been rigorously studied in children and raise difficult questions on how to manage a chronic inflammatory neurologic disease in a population of patients with developing central nervous and immune systems.

Development of Peptidomimetic Inhibitors of the ERG Gene Fusion Product in Prostate Cancer.

Transcription factors play a key role in the development of diverse cancers, and therapeutically targeting them has remained a challenge. In prostate cancer, the gene encoding the transcription factor ERG is recurrently rearranged and plays a critical role in prostate oncogenesis. Here, we identified a series of peptides that interact specifically with the DNA binding domain of ERG. ERG inhibitory peptides (EIPs) and derived peptidomimetics bound ERG with high affinity and specificity, leading to proteolytic degradation of the ERG protein. The EIPs attenuated ERG-mediated transcription, chromatin recruitment, protein-protein interactions, cell invasion and proliferation, and tumor growth. Thus, peptidomimetic targeting of transcription factor fusion products may provide a promising therapeutic strategy for prostate cancer as well as other malignancies.

Non-Covalent Microgel Particles Containing Functional Payloads: Coacervation of PEG-Based Triblocks via Microfluidics.

Well-defined microgel particles were prepared by combining coacervate-driven cross-linking of ionic triblock copolymers with the ability to control particle size and encapsulate functional cargos inherent in microfluidic devices. In this approach, the efficient assembly of PEO-based triblock copolymers with oppositely charged end-blocks allows for bioinspired cross-linking under mild conditions in dispersed aqueous droplets. This strategy enables the integration of charged cargos into the coacervate domains (e.g., the loading of anionic model compounds through electrostatic association with cationic end-blocks). Distinct release profiles can be realized by systematically varying the chemical nature of the payload and the microgel dimensions. This mild and noncovalent assembly method represents a promising new approach to tunable microgels as scaffolds for colloidal biomaterials in therapeutics and regenerative medicine.