The positive predictive value of MOG-IgG testing based on the 2023 diagnostic criteria for MOGAD.

Background: Myelin oligodendrocyte glycoprotein antibody associated disease (MOGAD) is a relatively new disease entity in the field of demyelinating disorders. Its first diagnostic criteria have recently been published. Objectives: We evaluated the positive predictive value (PPV) for MOG-IgG testing and report the clinical and radiologic features with respect to the recently published criteria. Methods: A retrospective study was conducted at three centers in Dallas, Texas. Patients with positive MOG-IgG testing on cell-based assays at any time were included. Positive cases were reviewed by at least two neuroimmunologists for fulfillment of the criteria. Results: We included 235 patients. The PPV of seropositivity at any time was 78.3% overall, 52.6% for low titer, and 90.1% for high titer. Children had a higher PPV than adults (93.9% versus 67.2%). Positive predictive value was 6.3% in those without a core clinical demyelinating attack. Children more often have the typical imaging features of MOGAD in optic neuritis than adults. Conclusions: We report a PPV of 78.3% for MOG-IgG testing using the 2023 MOGAD diagnostic criteria. Children had higher PPV and frequency of supporting imaging features. Careful consideration is necessary when assigning patients with no core demyelinating event and low titers a MOGAD diagnosis.

Subglottic Stenosis After Pediatric Tracheostomy.

OBJECTIVES: To determine the incidence of subglottic stenosis (SGS) in children after tracheostomy and identify risk factors for development. STUDY DESIGN: Retrospective cohort. METHODS: All patients (<18 years) undergoing tracheostomy at a tertiary children's hospital between 2015 and 2020 were included. Patients with a direct laryngoscopy (DL) concurrent with tracheostomy and a subsequent DL were included. Medical records, including operative reports, were reviewed to identify subglottic stenosis and associated risk factors. RESULTS: A total of 140 patients were included with mean age at tracheostomy of 2.4 years (standard deviation [SD]: 4.3) (median: 0.5 years, interquartile range [IQR]: 0.3-1.5 years) and gestational age of 33.8 weeks (SD: 5.9) (median: 36 weeks, IQR: 28-39 weeks). At initial DL, 24% (N = 34) had subglottic injury and 26% (N = 37) developed SGS. The incidence of SGS after tracheostomy was 11.5 cases per 100 patients per year. At tracheostomy, lower birth weight (1.8 vs. 2.3 kg, p = 0.005), shorter gestational age (31.8 vs. 34.6 weeks, p = 0.01), younger age (0.8 vs. 2.9 years, p = 0.01), lower weight (5.8 vs. 14.7 kg, p = 0.01), and subglottic injury (44% vs. 21%, p = 0.01) were associated with the development of SGS. Multivariable logistic regression analysis associated birth weight (odds ratio [OR]: 0.49, 95% confidence interval [CI]: 0.31-0.75, p = 0.001) and early subglottic injury (OR: 3.22, 95% CI: 1.31-7.88, p = 0.01) with SGS development. CONCLUSIONS: The incidence of SGS after pediatric tracheostomy is estimated at 11.5 cases per 100 patients per year. Low birth weight and subglottic injury at the time of tracheostomy were associated with SGS in this vulnerable population of children. LEVEL OF EVIDENCE: 3 Laryngoscope, 2024.

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.

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.

Risk-adjusted analysis of perioperative outcomes after the Sistrunk procedure.

Objectives: Thyroglossal duct cyst (TGDC) is the most common pediatric congenital neck mass. The Sistrunk procedure is the standard method of excision and is associated with low rates of recurrence. This study aimed to review our institution's outcomes following the Sistrunk procedure, specifically the rates of wound complications and cyst recurrence. Methods: This was a retrospective case series of pediatric patients undergoing the Sistrunk procedure from June 2009 to April 2021. Results: A total of 273 patients were included. Of these, 139 (53%) patients were male and 181 (66%) were white. The average age at the time of surgery was 7.1 years. The overall cyst recurrence rate was 11%. The most common wound complications were seroma (14%) and surgical site infections (SSIs) (12%). Wound complications were associated with prior history of cyst infection (odds ratio [OR] 1.97, 95% confidence interval [CI] 1.07-3.60, z-test 2.2, p = .03). Pediatric surgery was associated with fewer wound complications (OR 0.18; 95% CI 0.05-0.6, z-test -2.78, p = .005). However, pediatric surgery operated on fewer patients with a history of cyst infection (36% vs. 55%, p = .012). Drain placement and postoperative antibiotics did not affect rates of wound complications. Conclusions: Prior cyst infection is associated with increased rates of postoperative wound complications. Postoperative antibiotics and drain placement did not significantly affect complication rates. Level of Evidence: 4.

DEVO: an ontology to assist with dermoscopic feature standardization.

BACKGROUND: The utilization of dermoscopic analysis is becoming increasingly critical for diagnosing skin diseases by physicians and even artificial intelligence. With the expansion of dermoscopy, its vocabulary has proliferated, but the rapid evolution of the vocabulary of dermoscopy without standardized control is counterproductive. We aimed to develop a domain-specific ontology to formally represent knowledge for certain dermoscopic features. METHODS: The first phase involved creating a fundamental-level ontology that covers the fundamental aspects and elements in describing visualizations, such as shapes and colors. The second phase involved creating a domain ontology that harnesses the fundamental-level ontology to formalize the definitions of dermoscopic metaphorical terms. RESULTS: The Dermoscopy Elements of Visuals Ontology (DEVO) contains 1047 classes, 47 object properties, and 16 data properties. It has a better semiotic score compared to similar ontologies of the same domain. Three human annotators also examined the consistency, complexity, and future application of the ontology. CONCLUSIONS: The proposed ontology was able to harness the definitions of metaphoric terms by decomposing them into their visual elements. Future applications include providing education for trainees and diagnostic support for dermatologists, with the goal of generating responses to queries about dermoscopic features and integrating these features to diagnose skin diseases.

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.

Characteristics and Outcomes of Surgical Treatment for Bronchial Anomalies.

OBJECTIVES: Bronchial anomalies are rare but challenging conditions to treat in children, encompassing a variety of structural abnormalities that could compromise airway patency. This includes complete rings, absent cartilage, traumatic avulsions, bronchoesophageal fistulas, and cartilaginous sleeves. The objective of this study is to describe the characteristics and outcomes of a series of pediatric cases of bronchial anomalies that were treated by slide tracheobronchoplasty. METHODS: This is a single-institution retrospective case series of pediatric patients with bronchial anomalies who underwent surgical treatment between February 2004 and April 2020. Data extracted from electronic medical records included patient demographics, comorbidities, and surgical outcomes. RESULTS: There were a total of 29 patients included in the study, of which 14 had complete bronchial rings, 8 had absent bronchial rings, 4 had traumatic bronchial avulsions, 2 had bronchoesophageal fistulas, and one had a cartilaginous sleeve. Median follow-up time was 13 months (with a range of 0.5-213 months). The overall mortality rate was 17.2% (5 patients), all of whom had complete bronchial rings. Patients with complete bronchial rings also had a higher rate of not only cardiac (85.7%) and pulmonary comorbidities (85.7%) but also secondary airway lesions (78.6%). CONCLUSION: This is the largest series to date describing surgical treatment for bronchial anomalies. Complete bronchial rings were the most common anomaly treated, followed by absent rings and trauma. Surgical treatment can be successful but mortality rates are higher in patients with complete bronchial rings, possibly due to higher rates of pulmonary and cardiac comorbidities. LEVEL OF EVIDENCE: 4 Laryngoscope, 133:3334-3340, 2023.

Anti-NMDA Receptor Autoimmune Encephalitis: Diagnosis and Management Strategies.

Anti-N-methyl-D-aspartate receptor (NMDAR) encephalitis is the most recognized form of autoimmune encephalitis. It is characterized by a constellation of neurologic and psychiatric features along with positive NMDAR antibody, which is more sensitive and specific in CSF than serum. All patients should be screened at least once for neoplasm, with ovarian teratoma being found in most tumor-related cases. In the acute phase, first-line immunotherapy, often a combination of high-dose steroids, immunoglobulins, and/or plasma exchange, is strongly recommended. When first-line therapy fails, escalation to second-line immunotherapy, particularly rituximab, can further improve outcomes and prevent relapses. In refractory cases, additional complementary immunotherapies, such as cyclophosphamide, bortezomib and/or tocilizumab may be considered. Relapses occur in 10-30% of cases, mostly within the first two years from onset. Individuals should be followed up to determine if chronic maintenance therapy is required.

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.

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.

Discovery of a Highly Potent and Selective Dual PROTAC Degrader of CDK12 and CDK13.

Selective degradation of the cyclin-dependent kinases 12 and 13 (CDK12/13) presents a novel therapeutic opportunity for triple-negative breast cancer (TNBC), but there is still a lack of dual CDK12/13 degraders. Here, we report the discovery of the first series of highly potent and selective dual CDK12/13 degraders by employing the proteolysis-targeting chimera (PROTAC) technology. The optimal compound 7f effectively degraded CDK12 and CDK13 with DC50 values of 2.2 and 2.1 nM, respectively, in MDA-MB-231 breast cancer cells. Global proteomic profiling demonstrated the target selectivity of 7f. In vitro, 7f suppressed expression of core DNA damage response (DDR) genes in a time- and dose-dependent manner. Further, 7f markedly inhibited proliferation of multiple TNBC cell lines including MFM223, with an IC50 value of 47 nM. Importantly, 7f displayed a significantly improved antiproliferative activity compared to the structurally similar inhibitor 4, suggesting the potential advantage of a CDK12/13 degrader for TNBC targeted therapy.

Sense of control and conspiracy perceptions: Generative directions on a well-worn path.

We review recent research on the well-established relationship between sense of control and conspiracy perceptions, identifying challenges and promising new directions. First, we examine recent efforts to distinguish sense of control from adjacent but confounding psychological constructs (including uncertainty, threat, and powerlessness). Second, we discuss the limitations of experimentally manipulating sense of control and the trend toward natural experiments. Finally, we consider boundary conditions that moderate the relationship and clarify the types of conspiracy perceptions that sense of control predicts. By integrating past findings to more precisely define sense of control and its effects on cognition, we hope to identify productive avenues for future research.

Assessment of Environmental Demands of Age-Friendly Communities from Perspectives of Different Residential Groups: A Case of Wuhan, China.

Age-friendly communities (AFCs) are an important measure for fostering active aging. The key to achieving an age-friendly living environment is to construct or renovate it according to the residents' demands. To date, very few studies have attempted to delve into the AFCs' environmental demand from different groups' perspectives. Based on the theory of place attachment, the aim of this paper is to explore the demand diversity of different groups for the AFC environment. This study employs the nonparametric test and the Ordinal Priority Approach (OPA) to investigate the demands from the residents' perspectives, and is enhanced by incorporating experts' opinions. The empirical analysis shows that residents have a high level of demand for the physical environment (indoor and outdoor) and social environment (community services and social participation). At the same time, experts advocate the importance of using digital technologies to support people aged 45-65 who have higher requirements for a community environment than older adults. The findings also show that other backgrounds, such as gender, living arrangements, and year of the community establishment, lead to different demands. However, the impact of residents' education level, occupation, income, and self-care ability on the environmental demands is low. Based on the research findings, the paper provides some practical suggestions for the future design and development of AFCs.

Refractory Anti-NMDA Receptor Encephalitis in Early Pregnancy: A Case Report of Treatment Course and Pregnancy Outcomes.

BACKGROUND AND OBJECTIVES: Anti-N-methyl d-aspartate receptor (NMDAR) encephalitis classically affects women of childbearing age, producing a disproportionate number of pregnant women with anti-NMDAR encephalitis. The typical presentation includes progressive neuropsychiatric symptoms, seizures, and alterations in consciousness, all of which present potential risks to the fetus. First-line and second-line treatments similarly pose teratogenic potential; therefore, randomized studies with supportive data on pregnancy and fetal outcomes are lacking. METHODS: We present a case of refractory anti-NMDAR encephalitis during the first and second trimesters of pregnancy with the successful use of rituximab and cyclophosphamide and resultant healthy pregnancy. RESULTS: The patient was treated with an escalating immunotherapy regimen from 11 to 15 weeks of gestation, including steroids, plasma exchange, IV immunoglobulins, and rituximab, with no clinical response. At 16 weeks of gestation, she received cyclophosphamide with clinical improvement after 4 weeks. She subsequently gave birth to a healthy, term baby boy, who continued to do well at the follow-up. DISCUSSION: This case illustrates the effective use of cyclophosphamide in the second trimester of pregnancy for anti-NMDAR encephalitis. The use of second-line therapies remains an individualized decision because the relative risk-to-benefit ratio in pregnant women is incompletely understood.