Clinical Presentation, Management, and Diagnostic Performance of 2021 Criteria for Paraneoplastic Neurologic Syndromes in Childhood.

BACKGROUND AND OBJECTIVES: Paraneoplastic neurologic syndromes (PNSs) are remote neurologic immune-related effects of tumors. The clinical characteristics of pediatric PNSs remain unclear. We retrospectively examined the clinical characteristics of cases of pediatric PNSs and assessed the performance of the 2021 diagnostic criteria in children. METHODS: Patients hospitalized in the Beijing Children's Hospital between June 2015 and June 2023 and fulfilling the description of definite by 2004 diagnostic criteria of PNSs were included. A retrospective analysis of clinical characteristics was conducted, and the 2021 diagnostic criteria were applied to rediagnostic stratification. RESULTS: Among the 42 patients included, the most common neurologic syndrome was opsoclonus-myoclonus syndrome (OMS) (62%), followed by rapidly progressive cerebellar syndrome (26%). Most tumors were neuroblastomas (88%), with few being ovarian teratomas (10%). Approximately 71% (30/42) of patients were classified as definite and 24% (10/42) as probable according to the 2021 criteria. All cases judged as probable exhibited rapidly progressive cerebellar ataxia with neuroblastoma. For OMS, chemotherapy was administered based on the tumor's risk stage, accompanied by regular infusion of IV gamma globulin and oral steroids following tumor diagnosis. Twenty-one patients underwent regular follow-ups over 4.92 (0.58-7.58) years. The initial hospitalization recorded a median score of 12 (7-14) on the Mitchell and Pike OMS rating scale, decreasing to 0 (0-5) at the final follow-up. In cases of rapidly progressive cerebellar syndrome, a similar therapeutic regimen was used. Nine patients underwent regular follow-ups over 4.42 (1.17-7.50) years. The mean modified Rankin scale score at first hospitalization was 4 (3-4), reducing to 1 (0-4) at the final follow-up. Only 17% (5/30) of patients across both groups exhibited poor response to this regimen. Among these 5 patients, 4 belonged to the low-risk group (without chemotherapy). DISCUSSION: OMS followed by rapidly progressive cerebellar ataxia are the most common forms of PNSs in children and are associated with neuroblastoma. An aggressive approach with multiple immunotherapies may improve the prognosis of neuroblastoma-associated PNSs. The 2021 criteria perform well in pediatric PNSs. However, we propose upgrading the classification of antibody-negative rapidly progressive cerebellar ataxia with neuroblastoma to definite diagnosis. This adjustment aims to further improve the diagnostic efficacy of this diagnostic criterion in childhood.

Gender inequities in ENT: Insights from women speakers at American Head and Neck Society meetings.

BACKGROUND: Gender inequity exists across national speakers at American Head and Neck Society (AHNS) conferences. This qualitative study explores potential causes of this disparity by surveying women invited to speak at AHNS between 2007 and 2019 and examining advice, resources, and meaningful actions from "those who made it." METHODS: An internet search for contact information for the 131 female AHNS was performed. An electronic survey was distributed via email. Deidentified qualitative responses were coded by two independent researchers into themes. Themes characterize barriers that female head and neck (HN) surgeons face and describe ways to mitigate the impact of these for the next generation. RESULTS: Contact information for 73/131 female AHNS speakers was obtained via internet search. Email responses were received from 22/73 (30%). Of those, respondents specialized in otolaryngology (n = 17), medical oncology (n = 2), palliative care (n = 1), vascular surgery (n = 1), and thoracic surgical oncology (n = 1). All speakers worked in academic settings at varying stages of their career with 81.8% (18/22) of respondents fellowship-trained (primarily HN surgery). Concerns about gender disparity in ENT were grouped into the following themes: (1) recruiting women to ENT, (2) removing barriers to career advancement, (3) diversifying ENT's national presence, and (4) improving the broader culture of HN surgery. Respondents emphasized a need for diversifying leadership, early exposure to otolaryngology in medical school, and connecting students with female role models. Outstanding research, involvement at annual meetings, and committee membership were consistently deemed important for establishing a national presence in the field. Implicit bias, "boys clubs" culture, and burdensome childcare responsibilities were described as barriers to career advancement. CONCLUSIONS: While encouraging more women to enter otolaryngology residencies, increasing the number female role models and establishing strong mentoring networks may help to mitigate challenges. Meaningful progress requires the efforts of both male and female allies within the specialty. Simple solutions, such as educating on implicit bias, removing demographics from applications, and eliminating hidden penalties for maternity leave, may help improve diversity and mitigate barriers to career progression for underrepresented groups within ENT.

The Combined Contributions of Newborn Stress and Parenting Stress on Toddler Language Development.

OBJECTIVE: To examine the longitudinal associations between newborn neurobehavioral stress signs, maternal parenting stress, and several indices of toddler language development. STUDY DESIGN: Participants include 202 mother-infant dyads (104 girls). We measured stress signs in neonates in the hospital at least 24 hours after birth using the Neonatal Intensive Care Unit Network Neurobehavioral Scale. At 7 months, parenting stress (competence, attachment, and role restriction) was assessed using the Parenting Stress Index. At 18 months, mothers completed the Communicative Development Inventories, which measured toddler gesturing, expressive vocabulary, and receptive vocabulary. Longitudinal path modeling was used to estimate associations between neonatal stress signs, parenting stress, and toddler language, and a model was generated for each language outcome. Child sex, birth weight, and family income were included as covariates. RESULTS: Infants who exhibited greater neurobehavioral stress signs at birth produced significantly fewer social-communicative gestures at 18 months of age. Among infants whose mothers reported low (but not high) levels of parenting stress during the first postnatal year, newborn stress signs were negatively associated with 18-month-olds' receptive vocabulary size. Neither newborn stress signs nor parenting stress were significantly related to toddler expressive vocabulary size. CONCLUSIONS: Our findings uncover a negative association between newborn stress signs and toddler gesturing. Furthermore, our results suggest that caregiver stress and neonatal stress signs interact to predict toddler receptive vocabulary. Taken together, these results demonstrate that some neonates who exhibit increased neurobehavioral stress signs may be at heightened risk for experiencing language difficulties. These children may benefit from additional support in infancy.

Interactions among stress, behavioral inhibition, and delta-beta coupling predict adolescent anxiety during the COVID-19 pandemic.

The COVID-19 pandemic brought about unprecedented changes and uncertainty to the daily lives of youth. The range of adjustment in light of a near-universal experience of COVID restrictions highlights the importance of identifying factors that may render some individuals more susceptible to heightened levels of anxiety during stressful life events than others. Two risk factors to consider are temperamental behavioral inhibition (BI) and difficulties in emotion regulation (ER). As such, the current paper focused on BI examined prior to COVID, because of its developmental link to anxiety and ER, as difficulties may be associated with differences in anxiety. We examined a neurocognitive marker of ER processes, delta-beta coupling (DBC). The current paper had two goals: (1) to examine BI in relation to COVID-related worry and social anxiety experienced during the pandemic, and (2) to explore the role of individual differences in early DBC in the relationship between BI and anxiety outcomes 6 months apart during COVID-19 (n = 86; T1 Mage  = 15.95, SD = 1.73; T6 Mage  = 16.43, SD = 1.73). We found support for the moderating role of DBC in the relationship between BI levels and social anxiety disorder (SAD) symptom severity during the pandemic. Here, high BI was predictive of increased SAD symptom levels in adolescents with stronger DBC.

Aging with my family: a grounded theory approach on the role of family when aging as foreign-born.

BACKGROUND: Research indicates that it is the quality of the closest relationships in the mixture of social relations that matters most for older adults. For older foreign-born, especially those who migrate late in life, the family is often the only socioeconomical resource they can lean on. This study aims to explore how older foreign-born perceive the role of family as they age. METHODS: The study design has a grounded theory approach. Data consist of individual open-ended interviews with 15 foreign-born informants aged between 60 and 85 years old who migrated to Sweden as adults from various parts of the world. RESULTS: The findings demonstrate that family was an essential part of the informants' lives as they lived for their families and their families lived for them. Family solidarity was described as a cultural heritage they took over from their original families and a cultural heritage they wished to pass on to their future generations. They found that this was what separated them as foreign-born from native-born. Memories of their parents reminded them of their biological, social, and cultural heritages. The intimate relationship with their spouses in a life course had served as a source of validation of their individual identities and promoted personal growth and self-esteem. The role as a loving and caring parent entailed a sense of accomplishment and satisfaction for the life lived. And now as grandparents, the role as a link between the family's historical heritage and the future generation entailed not only a sense of coherence as they aged but also hope and meaning beyond their own lives. CONCLUSIONS: The older foreign-born experienced life satisfaction as they aged with their families. Family meant community and solidarity. It was in the family that they found their distinct roles that had defined them. Family was an indispensable part of their social identity. The findings highlight the importance of older foreign-born being studied from a family and lifetime perspective.

A Two-dimensional Metal-Organic Framework as Promising Cathode for Advanced Lithium Storage.

Anthraquinone electrode materials are promising candidates for lithium-ion batteries (LIBs) due to the abundance of anthraquinone and the high theoretical capacity, and good reversibility of the anthraquinone electrodes. However, the active anthraquinone materials are soluble in organic electrolytes, resulting in a sharp decay of capacity during the charge and discharge processes. Herein, we report on a two-dimensional calcium anthraquinone 2,3-dicarboxy metal-organic framework (2D CaAQDC MOF) fabricated using a simple hydrothermal method. The 2D CaAQDC MOF not only effectively inhibits the dissolution of active electrode substances into the electrolyte, but also promotes the diffusion of lithium ion into the pores of the MOF. When used as a cathode for the LIBs, the resulting CaAQDC electrode delivers a high specific capacity of ~100 mAh g-1 at a current density of 50 mA g-1 after 200 cycles, demonstrating its good cycle stability. Even at a high current density of 200 mA g-1 , the CaAQDC electrode exhibits a specific capacity of ~60 mAh g-1 . The fabricated 2D coordination polymers effectively restrains the dissolution of anthraquinone into the organic electrolyte and enhances the structural stability, which greatly improves the electrochemical performance of anthraquinone. These research results offer a rational molecular design strategy to address the dissolution of this and other active organic electrode materials.

Encephalitis is an Important Phenotype of Myelin Oligodendrocyte Glycoprotein Antibody-Associated Diseases: A Single-Center Cohort Study.

BACKGROUND: Myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD) is considered a demyelinating disease of the central nervous system, but an increasing number of encephalitis cases associated with MOG antibodies have been reported recently. METHODS: This was a single-center, retrospective study. All data for pediatric patients with MOGAD diagnosed at Beijing Children's Hospital from January 2017 to January 2022 were collected. Clinical characteristics and outcomes were analyzed, and treatment responses were compared between the rituximab (RTX) and mycophenolate mofetil (MMF) groups. RESULTS: A total of 190 patients (age range: 5 months to 16 years; median age: 7.2 years; females: 97) were included in this study. The phenotypes of the first attack included acquired demyelinating syndromes (105 [55%]), encephalitis other than acute disseminated encephalomyelitis (82 [43%]), and isolated meningitis (3 [2%]). After a median follow-up of 30.4 months (interquartile range: 14.8-43.7), 64 (34%) patients had relapses. Fifty-one of the 64 (80%) patients who had relapse received maintenance therapy, including MMF (41), RTX (11), maintenance intravenous immunoglobulin (two), and tocilizumab (two). The annualized relapse rates decreased significantly after treatment in both the RTX and MMF cohorts (P < 0.05); however, there were no significant differences between the two groups (P = 0.56). A total of 178 (94%) patients had complete (175 patients) or almost complete (three patients) recovery (modified Rankin scale [mRS] < 2), and 12 had moderate to severe deficits (mRS ≥ 2). CONCLUSIONS: The spectrum of pediatric MOGAD is broader than previously reported and includes demyelinating syndromes and encephalitis. Encephalitis is an important initial phenotype observed in pediatric patients with MOGAD.

Social skills deficits and self-appraisal biases in children with social anxiety disorder.

Social Anxiety Disorder is highly prevalent among children and leads to poor long-term outcomes if left untreated. Theoretical models of anxiety differ in whether children with Social Anxiety Disorder experience objective social skills deficits, negative self-interpretation biases, or some combination of the two. This pilot study evaluated evidence in support of the "deficit" and "bias" models. Approval was obtained from the ethics committee of a large private university in Cambridge, MA, USA, and data collection was completed in 2015. We recruited 68 parent-child dyads for a study in which anxious children (with Social Anxiety Disorder) and non-anxious children underwent a child-adapted version of the Trier Social Stress Test. Children were aged 8-14, 67.6% male, and self-identified as 54.4% White, 7.4% Black, 4.4% Latinx, 13.2% Asian, 14.7% multiethnic, and 5.9% "other" or no response. Performance ratings were obtained from children, their parents, and external observers. We found evidence of both specific social skills deficits and self-appraisal biases in anxious children. Anxious children struggled with signs of physical discomfort but not with actual speech content. Although children were generally able to accurately evaluate their social performance, older anxious children were most self-critical. Parents were similarly accurate in appraisals of their children's social performance. Anxious children responded favorably to positive feedback with improved self-evaluations of performance and decreased anxiety. Findings suggest that a comprehensive "integrated" theoretical model of Social Anxiety Disorder should include both skills deficits and self-appraisal biases.

The Impact of a Digital Weight Loss Intervention on Health Care Resource Utilization and Costs Compared Between Users and Nonusers With Overweight and Obesity: Retrospective Analysis Study.

BACKGROUND: The Noom Weight program is a smartphone-based weight management program that uses cognitive behavioral therapy techniques to motivate users to achieve weight loss through a comprehensive lifestyle intervention. OBJECTIVE: This retrospective database analysis aimed to evaluate the impact of Noom Weight use on health care resource utilization (HRU) and health care costs among individuals with overweight and obesity. METHODS: Electronic health record data, insurance claims data, and Noom Weight program data were used to conduct the analysis. The study included 43,047 Noom Weight users and 14,555 non-Noom Weight users aged between 18 and 80 years with a BMI of ≥25 kg/m² and residing in the United States. The index date was defined as the first day of a 3-month treatment window during which Noom Weight was used at least once per week on average. Inverse probability treatment weighting was used to balance sociodemographic covariates between the 2 cohorts. HRU and costs for inpatient visits, outpatient visits, telehealth visits, surgeries, and prescriptions were analyzed. RESULTS: Within 12 months after the index date, Noom Weight users had less inpatient costs (mean difference [MD] -US $20.10, 95% CI -US $30.08 to -US $10.12), less outpatient costs (MD -US $124.33, 95% CI -US $159.76 to -US $88.89), less overall prescription costs (MD -US $313.82, 95% CI -US $565.42 to -US $62.21), and less overall health care costs (MD -US $450.39, 95% CI -US $706.28 to -US $194.50) per user than non-Noom Weight users. In terms of HRU, Noom Weight users had fewer inpatient visits (MD -0.03, 95% CI -0.04 to -0.03), fewer outpatient visits (MD -0.78, 95% CI -0.93 to -0.62), fewer surgeries (MD -0.01, 95% CI -0.01 to 0.00), and fewer prescriptions (MD -1.39, 95% CI -1.76 to -1.03) per user than non-Noom Weight users. Among a subset of individuals with 24-month follow-up data, Noom Weight users incurred lower overall prescription costs (MD -US $1139.52, 95% CI -US $1972.21 to -US $306.83) and lower overall health care costs (MD -US $1219.06, 95% CI -US $2061.56 to -US $376.55) per user than non-Noom Weight users. The key differences were associated with reduced prescription use. CONCLUSIONS: Noom Weight use is associated with lower HRU and costs than non-Noom Weight use, with potential cost savings of up to US $1219.06 per user at 24 months after the index date. These findings suggest that Noom Weight could be a cost-effective weight management program for individuals with overweight and obesity. This study provides valuable evidence for health care providers and payers in evaluating the potential benefits of digital weight loss interventions such as Noom Weight.

Identifying the potential impact of a multidisciplinary outpatient antimicrobial therapy program in an area of high social vulnerability.

Background: Outpatient parenteral antimicrobial therapy (OPAT) and complex outpatient antimicrobial therapy (COpAT) are common practice in the management of infectious diseases (IDs). However, providing OPAT/COpAT can pose significant challenges pre- and post-discharge, particularly in vulnerable patient populations. Objectives: The objective of this study is to assess outpatient complications related to OPAT/COpAT in patients discharged with a home health services referral and to identify pre- and post-discharge intervention opportunities and the associated cost-savings that could be achieved with a multidisciplinary ID team-run OPAT/COpAT program. Design/methods: This is a retrospective cohort study of patients who were discharged with OPAT/COpAT through home health services over a 3-month study period. Data on potential pre-discharge interventions and post-discharge complications were recorded. Results: Medication-related issues were the most common pre-discharge complications, accounting for more than 50% of identified intervention opportunities. More than half of the included patients experienced at least one documented outpatient complication post-discharge with peripherally inserted central catheter-line-related complication (20.7%) being the most common issue. Using previously published cost-estimates, the implementation of a designated pre- and post-discharge OPAT/COpAT program could have saved over $100,000 over the 3-month study period. Conclusion: A multidisciplinary OPAT/COpAT program located in a high social vulnerable area can help reduce complications related to a patient's antimicrobial therapy. Medication-related issues represent a major area for potential intervention. Our findings suggest that a multidisciplinary ID team will have ample opportunities to improve the transition of care, at both pre- and post-discharge, for patients requiring antimicrobial therapy.

Examining transactional associations between maternal internalizing symptoms, infant negative emotionality, and infant respiratory sinus arrhythmia.

The current study examined transactional associations between maternal internalizing symptoms, infant negative emotionality, and infant resting respiratory sinus arrhythmia (RSA). We used data from the Longitudinal Attention and Temperament Study (N = 217) to examine the associations between maternal internalizing symptoms, infant negative emotionality, and infant resting RSA from 4-months to 18-months using a random-intercepts cross-lagged panel model. We found that mothers with higher average internalizing symptoms have infants with higher levels of resting RSA. However, there were no stable, between-individual differences in infant negative emotionality across time. Additionally, we found significant negative within-dyad cross-lagged associations from maternal internalizing symptoms to subsequent measures of infant negative emotionality, as well as a significant negative cross-lagged association from maternal internalizing symptoms to child resting RSA after 12-months of age. Lastly, we find evidence for infant-directed effects of negative emotionality and resting RSA to maternal internalizing symptoms. Results highlight the complex, bidirectional associations in maternal-infant dyads during the first two years of life, and the importance of considering the co-development of infant reactivity and regulatory processes in the context of maternal internalizing symptoms.

Development of a rat model of lymphedema and the implantation of a collagen-based medical device for therapeutic intervention.

Secondary lymphedema is a common condition among cancer survivors, and treatment strategies to prevent or treat lymphedema are in high demand. The development of novel strategies to diagnose or treat lymphedema would benefit from a robust experimental animal model of secondary lymphedema. The purpose of this methods paper is to describe and summarize our experience in developing and characterizing a rat hindlimb model of lymphedema. Here we describe a protocol to induce secondary lymphedema that takes advantage of micro computed tomography imaging for limb volume measurements and visualization of lymph drainage with near infrared imaging. To demonstrate the utility of this preclinical model for studying the therapeutic benefit of novel devices, we apply this animal model to test the efficacy of a biomaterials-based implantable medical device.

Examining the impact of racial disparities on Clostridioides difficile infection outcomes at a Southern California academic teaching hospital.

Racial differences in Clostridioides difficile infection (CDI) outcomes have been reported. In this study, minoritized patients with CDIs had prolonged hospitalizations and increased intensive care unit admissions. Chronic kidney disease was shown to partially mediate the relationship between race or ethnicity and severe CDI. Our findings suggest potential areas for equitable interventions.

Clinical and Radiologic Features Among Children With Myelin Oligodendrocyte Glycoprotein Antibody-Associated Myelitis.

BACKGROUND: Myelin oligodendrocyte glycoprotein (MOG) antibody-associated disease (MOGAD) often manifests as optic neuritis, transverse myelitis(TM), and acute disseminated encephalomyelitis. Patients with a TM phenotype are at high risk for neurological sequelae, so recognizing the characteristics of MOG-IgG myelitis is essential for early, accurate diagnosis and treatment. METHODS: This was a single-center retrospective study. Pediatric MOG antibody-associated disease patients who had clinical myelitis were recruited for this study. Data on clinical and radiologic features and outcomes were retrospectively collected. RESULTS: Thirty-four patients (age range: 6 months to 13 years; median age, 7 years; female, 16) were enrolled in this study. As one patient had two clinical episodes of myelitis, 35 episodes were included. Isolated transverse myelitis was the initial manifestation in 28 (82%) patients. The most frequent clinical features of MOG-IgG myelitis were weakness and neurogenic bladder, and 80% were better than wheelchair-dependent at the nadir. There was a high presentation of weakness (91%), bowel/bladder dysfunction (63%), and sensory dysfunction (46%), and 80% were better than wheelchair-dependent at the nadir. In addition, seven patients (20%) had radicular pain, and six had flaccid areflexia. Magnetic resonance imaging features were often longitudinally extensive (63%) and prominently involved gray matter (H-sign) (63%), accompanied by leptomeningeal enhancement (4/14.29%) and spinal root enhancement (6/14.43%). At the final follow-up (median, 28 months; range, 8-109 months), 10 patients (29%) had developed one or more relapses, spinal cord lesions resolved entirely in 11 of 22 children (50%), and none had appreciable spinal cord atrophy. At the final follow-up, most patients had favorable outcomes, with median (interquartile range) Expanded Disability Status Scale scores of 0 (range, 0-2), four patients (12%) had sphincter dysfunction, and one patient had gait problems. CONCLUSIONS: Pediatric MOG-IgG myelitis clinically presents with weakness and bowel and bladder dysfunctions. Prominent involvement of the gray matter, leptomeningeal enhancement, and spinal root enhancement are common in pediatric MOG-IgG myelitis.

Place in Therapy of Cyclin-Dependent Kinase 4/6 Inhibitors in Breast Cancer: A Targeted Literature Review.

Cyclin-dependent kinase 4 and 6 inhibitors (CDK4/6i) are the preferred regimen for patients with hormone receptor-positive and human epidermal growth factor receptor 2-negative (HR+/HER2-) advanced or metastatic breast cancer. However, the optimal treatment sequencing for CDK4/6i with other available therapeutic options is unclear. We conducted a targeted literature review to identify the current evidence on CDK4/6i treatment patterns in patients with breast cancer. The search was initially conducted in October 2021 and subsequently updated in October 2022. Biomedical databases and gray literature were searched, and bibliographies of included reviews were screened for relevant studies. The search identified ten reviews published since 2021 and 87 clinical trials or observational studies published since 2015. The included reviews discussed CDK4/6i usage with or without endocrine therapy (ET) in first-line and second-line treatment for patients with HR+/HER2- advanced or metastatic breast cancer, followed by ET, chemotherapy, or targeted therapy with ET. Clinical studies reported similar treatment sequences consisting of ET, chemotherapy, or targeted therapy with ET prior to CDK4/6i with ET, followed by ET monotherapy, chemotherapy, targeted therapy with ET, or continued CDK4/6i with ET. Current evidence suggests CDK4/6i are effective for HR+/HER2- advanced or metastatic breast cancer in earlier lines of therapy. Efficacy of CDK4/6i as measured by progression-free survival and overall survival was similar within a line of therapy regardless of the type of prior therapy. Survival on different post-CDK4/6i treatments was also similar within the same line of therapy. Additional research is needed to investigate the optimal place in therapy of CDK4/6i and the sequencing of treatments following progression on CDK4/6i.

Racial disparities among candidemic patients at a Southern California teaching hospital.

Racially and ethnically minoritized (REM) patients are disproportionately affected by infectious diseases, including candidemia. REM patients with candidemia were significantly younger, with trends toward more risk factors for candidemia and longer lengths of stay. Although Candida parapsilosis was more common in REM patients, there were no differences in mortality rates.

Autonomic nervous system activity moderates associations between temperament and externalizing behaviors in early childhood.

Temperamental risk, such as surgency, negative affect, and poor effortful control, has been posited as a predictor of externalizing symptom development. However, autonomic nervous system (ANS) activity underlying processes of reactivity and regulation may moderate associations between early temperament and later externalizing behaviors during early childhood. The aim of the present study was to examine how interactions between resting sympathetic (SNS) and parasympathetic (PNS) activity at age 5 may moderate associations between temperamental risk at age 3 and externalizing behavior at age 6 (n = 87). Results demonstrate different interactions between resting ANS activity and temperamental risk to predict externalizing behaviors. For children with lower SNS activation at rest, surgency was positively associated with externalizing behaviors. Negative affect was positively associated with externalizing behaviors except when there were either high levels of SNS and PNS activity or low levels of SNS and PNS activity. Effortful control was not associated with externalizing behaviors, though SNS and PNS activity interacted to predict externalizing behaviors after accounting for effortful control. Taken together, the results highlight the importance to examine multisystem resting physiological activity as a moderator of associations between temperamental risk and the development of externalizing  behaviors.

High levels of cerebrospinal fluid soluble triggering receptor expressed on myeloid cells 2 might be a biomarker of activity in pediatric patients with MOG-AD.

Myelin oligodendrocyte glycoprotein antibody disease (MOG-AD) is characterized by its monophasic or relapsing course and inflammatory demyelinating condition which is unable to be classified in typical multiple sclerosis (MS) or other known neuroinflammatory conditions. In the condition of neuroinflammatory, activated microglia are essential for demyelination. The secreted ectodomain of soluble triggering receptor expressed on myeloid cells 2 (sTREM2), expressed by microglial cells, is associated with abnormal biological pathways. It is known that the cerebrospinal fluid (CSF) sTREM2 concentration is much higher in neuroinflammatory and neurodegeneration diseases. However, the role of activated microglia has not been reported in MOG-AD pediatric patients. For the first time, the increased CSF and serum sTREM2 concentration in pediatric patients with MOG-AD is investigated in this work, showing evidence of microglia activation in MOG-AD. CSF sTREM2 levels significantly correlated with clinical inflammatory indexes and adapted modified Rankin Scale score, indicating the potential value of sTREM2 as a severity biomarker.

Mycophenolate mofetil: An alternative disease-modifying agent for MOG-IgG-associated disorders in childhood: A single-center bidirectional cohort study.

OBJECTIVE: To evaluate the efficacy of mycophenolate mofetil (MMF) in the treatment of childhood MOG-IgG-associated disorder (MOGAD). METHODS: Thirty patients diagnosed with relapsing MOGAD and treated with MMF for >1 year from a childhood MOGAD ambispective cohort were included in the study. The clinical characteristics, therapeutic regimen, side effects, annualized relapse rate (ARR), and Expanded Disability Status Scale (EDSS) scores of these patients were evaluated. RESULTS: The median age of disease onset was 7.05 (2.50-12.75) years. The male to female ratio was 1:1.31. All patients used MMF as first-line maintenance treatment. The median time to add MMF from disease onset was 1.08 (0.25-5.00) year. The median number of attacks before MMF initiation was 2 (2 - 8). The median duration of MMF therapy was 2.13 (1.00-3.58) years. Twenty (66.67%) patients did not experience further attacks during MMF therapy. The Kaplan-Meier curves showed a 3-year relapse-free rate of 59.8% (95% CI, 36.62-76.88%). ARR decreased during MMF therapy (0 (0 - 1.72) vs. 1.25 (0.60-4.00); P < 0.05). EDSS stabilized during MMF therapy (1.0 (0 - 2.0) vs. 0 (0 - 2.0); P = 0.206). None of the patients stopped the use of MMF due to intolerable side effects. Onset age, sex, phenotype of the first attack, ARR before MMF, MOG-IgG titers, and combined long-term prednisone (prednisone <10 mg daily for patients >40 kg or <5 mg daily for patients ≤40 kg longer than 6 months) did not predict recurrence during MMF therapy in univariate analysis. CONCLUSIONS: MMF was effective and safe for treating childhood MOGAD. No clinical feature that could predict efficacy of MMF was found in pediatric patients with MOGAD.

Are fearful boys at higher risk for anxiety? Person-centered profiles of toddler fearful behavior predict anxious behaviors at age 6.

Dysregulated fear (DF), the presence of fearful behaviors in both low-threat and high-threat contexts, is associated with child anxiety symptoms during early childhood (e.g., Buss et al., 2013). However, not all children with DF go on to develop an anxiety disorder (Buss and McDoniel, 2016). This study leveraged the data from two longitudinal cohorts (N = 261) to (1) use person-centered methods to identify profiles of fearful temperament, (2) replicate the findings linking DF to anxiety behaviors in kindergarten, (3) test if child sex moderates associations between DF and anxiety behaviors, and (4) examine the consistency of findings across multiple informants of child anxiety behaviors. We identified a normative fear profile (low fear in low-threat contexts; high fear in high-threat contexts), a low fear profile (low fear across both low- and high-threat contexts) and a DF profile (high fear across both low- and high-threat contexts). Results showed that probability of DF profile membership was significantly associated with child self-reported overanxiousness, but not with parent-reported overanxiousness. Associations between DF profile membership and overanxiousness was moderated by child sex such that these associations were significant for boys only. Additionally, results showed that probability of DF profile membership was associated with both parent-reported social withdrawal and observations of social reticence, but there were no significant associations with child self-report of social withdrawal. Results highlight the importance of considering person-centered profiles of fearful temperament across different emotion-eliciting contexts, and the importance of using multiple informants to understand associations with temperamental risk for child anxiety.