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The purpose of this study was to evaluate if focal cortical dysplasia (FCD) co-localization to cortical functional networks is associated with the temporal distribution of epilepsy onset in FCD.International (20 center), retrospective cohort from the Multi-Centre Epilepsy Lesion Detection (MELD) project. Patients included if3 years old, had 3D pre-operative T1 magnetic resonance imaging (MRI; 1.5 or 3 T) with radiologic or histopathologic FCD after surgery. Images processed using the MELD protocol, masked with 3D regions-of-interest (ROI), and co-registered to fsaverage_sym (symmetric template). FCDs were then co-localized to 1 of 7 distributed functional cortical networks. Negative binomial regression evaluated effect of FCD size, network, histology, and sulcal depth on age of epilepsy onset. From this model, predictive age of epilepsy onset was calculated for each network.Three hundred eighty-eight patients had median age seizure onset 5 years (interquartile range [IQR] = 3-11 years), median age at pre-operative scan 18 years (IQR = 11-28 years). FCDs co-localized to the following networks: limbic (90), default mode (87), somatomotor (65), front parietal control (52), ventral attention (32), dorsal attention (31), and visual (31). Larger lesions were associated with younger age of onset (p = 0.01); age of epilepsy onset was associated with dominant network (p = 0.04) but not sulcal depth or histology. Sensorimotor networks had youngest onset; the limbic network had oldest age of onset (p values 0.05).FCD co-localization to distributed functional cortical networks is associated with age of epilepsy onset: sensory neural networks (somatomotor and visual) with earlier onset, and limbic latest onset. These variations may reflect developmental differences in synaptic/white matter maturation or network activation and may provide a biological basis for age-dependent epilepsy onset expression. ANN NEUROL 2022;92:503-511.

STUDY OBJECTIVE: Most 911 calls result in ambulance transport to an emergency department. In some cases, transport is refused or deemed unnecessary. The frequency of pediatric non-transport is unknown. Our primary objective was to describe the proportion of pediatric EMS activations resulting in non-transport. Our secondary objective was to identify patient, community, and EMS agency factors associated with pediatric non-transport. METHODS: We conducted a cross-sectional study using 2019 data from the National EMS Information System registry. We compared non-transport rates for children (< 18 y/o), adults (18 – 60 y/o) and elderly (>60 y/o) patients. We then used generalized estimating equations to identify factors associated with pediatric non-transport while accounting for geographical clustering. RESULTS: There were 21,931,490 EMS activations, including 1,403,454 pediatric 911 responses. 30% of pediatric 911 responses resulted in non-transport. Non-transport was less likely for adults (19%, OR 0.54 [0.54, 0.55]) and elderly patients (13%, OR 0.35 [0.35, 0.36]). The most common pediatric non-transport dispositions were: refused evaluation/care, and treated/released. Non-transport was associated with: pulmonary (aOR 3.84 [3.30, 4.48]) and musculoskeletal chief complaints (aOR 3.75 [3.22, 4.36]). Non-transport was more likely for: rural EMS calls (aOR 1.28 [1.24, 1.32]); calls classified by EMS as Lower Acuity (aOR 7.88 [5.98, 10.38]); and Tribal EMS agencies (aOR 3.49 [3.09, 3.94]). CONCLUSION: Almost one-third of pediatric 911 activations result in non-transport. Although very few children have been included in pilots of alternate transport processes to date, non-transport is actually more common in children than adults. More work is needed to understand better the patient safety and economic implications of this practice.

Patients with sickle cell disease (SCD) need frequent health maintenance visits and may face barriers accessing care. Telemedicine, during COVID pandemic, has provided a unique model of care to improve access; however, potential barriers and satisfaction with its use in SCD have not been fully evaluated.To determine caregiver, patient, and healthcare provider (HCP) perspectives and satisfaction with telemedicine in healthcare delivery.We surveyed patients with SCD, caregivers, and HCP, who participated in at least one telemedicine visit from March 2020 to June 2021, using the Telemedicine Usability Questionnaire (TUQ). We also accessed and compared the Press Ganey surveys completed by families who completed a telemedicine or in-person visit. Data were summarized using descriptive statistics. The internal reliability of TUQ was assessed using Cronbach's coefficient alpha. Press Ganey data comparing satisfaction with telemedicine versus in-person visits were analyzed by Mann-Whiney U test.Fifty-two patients/caregivers and 10 HCP completed the survey. Patients/caregivers rated satisfaction "excellent" in the five areas (Usefulness, Ease of use, Effectiveness, Reliability and Satisfaction). HCP rated Usefulness, Ease of use, Effectiveness, Satisfaction as "good," and Reliability as "excellent." Press Ganey scores for satisfaction with care for telemedicine and in-person visits were not statistically different (p .05).We found high satisfaction for caregivers and patients as well as HCP in the delivery of clinical services via telemedicine for SCD. We suggest that telemedicine is a viable option for this population and may help overcome the barriers SCD families often face accessing care.

Background Antenatal and neonatal viral exposure may put the developing brain at risk for abnormal neurodevelopment. A clinical follow-up program was created in the Congenital Infection Program at Children’s National Hospital to follow infants with in utero or early life exposure to SARS-CoV-2. The aim of this study was to determine if infants with early SARS-CoV-2 exposure have abnormal neurodevelopment in infancy. Methods We performed a retrospective review of all infants evaluated in the follow-up program between 3/2020 – 11/2021. Demographic details, SARS-CoV-2 infection/testing data, pregnancy/birth data, and specialty consult and NICU records were extracted from infants’ medical charts. Infants were divided into 3 SARS-CoV-2 exposure groups: 1) antenatal exposure to symptomatic mother, 2) antenatal exposure to asymptomatic mother, 3) neonatal infection. All infants received a neurologic exam and developmental screening with the Ages and Stages Questionnaire (ASQ) in 5 domains (Communication, Gross Motor, Fine Motor, Problem Solving, Personal-Social) during their evaluation. The ASQ accounts for prematurity. Outcomes of interest were an abnormal neurologic exam or ASQ scores close to or below suggested cut-offs. Multivariate analysis was used to study correlations between exposure group and neurodevelopmental outcomes. Results Thirty-five infants were seen for up to 3 outpatient visits. Most infants (83%) were exposed in utero – 16 to symptomatic mothers (Group 1) and 12 to asymptomatic mothers (Group 2); 1 chart did not have symptom data. Six were exposed only as a neonate (Group 3). Group 1 had abnormal neurologic exams at mean (SD) age 112 (24) days (Table 1) and ASQ scores close to or below cut-offs for all domains (Fig. 1) more frequently than Groups 2 or 3. Group 1 was more likely to score below any ASQ cutoff compared to Group 2 (P=.04); of the 5 domains, differences were significant for Fine Motor (P=.01) and Personal-Social (P=.02). Conclusion Early SARS-CoV-2 exposure may impact infant development, especially among those exposed in utero to a symptomatic mother. Vaccination and other precautions to reduce spread and symptoms may protect against early neurodevelopmental delays. Future work should prioritize longitudinal follow-up of children with early SARS-CoV-2 exposure. Disclosures All Authors: No reported disclosures.

Background Patients admitted to the pediatric intensive care unit (PICU) are frequently evaluated for bacterial infections and initiated on antibiotic regimens that include a MRSA-active agent even though invasive MRSA infections are rare in this population. The MRSA PCR nasal swab (MRSA-PCR) is a non-invasive test for MRSA colonization that has been shown within adult ICUs to have a high negative predictive value (NPV), making it a potentially valuable tool for antimicrobial stewardship. This study evaluated the performance of the MRSA-PCR in predicting invasive MRSA infection in critically ill pediatric patients. Methods A retrospective cohort study was performed in a 44-bed PICU from January 2013 to December 2018 when it was protocol for all admissions to be screened with a MRSA-PCR. Patients who had both a MRSA-PCR and cultures obtained to evaluate for invasive infection within seven days were included in the study. Invasive MRSA infection was defined by the isolation of MRSA from clinical cultures along with infectious signs and symptoms. A random sample comprising 55% of the patient population was evaluated. We calculated sensitivity, specificity, positive predictive value (PPV) and NPV of the MRSA-PCR for confirmed invasive MRSA infection. Results Of the 4,410 patients reviewed, 1,961 patients met inclusion criteria (45% female, mean age 7.4 yrs. [birth-19.9 yrs.]). MRSA-PCR was positive in 13.5% of patients. Invasive MRSA infection was identified in 25 patients (2 blood, 19 respiratory, 2 soft tissue, 1 pleural fluid, and 1 urine culture) equaling 1.2% of encounters and an incidence rate of 1.1 case per 1,000 patient days. The MRSA-PCR demonstrated a PPV of 8.7% and a NPV of 99.8% (see table). Conclusion The MRSA-PCR has a poor PPV but a very high NPV for invasive MRSA infection in critically ill pediatric patients, a result that is congruent with what has been reported in the adult literature. The high NPV of the MRSA-PCR in this vulnerable patient population makes it a potentially powerful tool for antimicrobial stewardship. Creation of protocols to guide antimicrobial selection based on MRSA-PCR results may lead to a significant reduction in unnecessary antibiotic exposure, drug level monitoring, and patient risk of renal injury or adverse reactions. Disclosures All Authors: No reported disclosures.

Children with in utero Zika virus (ZIKV) exposure without congenital Zika syndrome (CZS) are at risk for abnormal neurodevelopment. Preschool-age outcomes for children with antenatal ZIKV exposure have not yet been established.Children with in utero ZIKV exposure and non-exposed controls had neurodevelopmental evaluations at age 3-5 years in Sabanalarga, Colombia. Cases did not have CZS and were previously evaluated prenatally through age 18 months. Controls were born before ZIKV arrival to Colombia. Neurodevelopmental assessments included Pediatric Evaluation of Disability Inventory (PEDI-CAT), Behavior Rating Inventory of Executive Function (BRIEF-P), Bracken School Readiness Assessment (BSRA), and Movement Assessment Battery for Children (MABC). Family demographics and child medical history were recorded.Fifty-five ZIKV-exposed children were evaluated at mean age 3.6 years and 70 controls were evaluated at 5.2 years. Family demographics were similar between groups. BRIEF-P t-scores were higher for cases than controls in shift and flexibility domains. Cases had lower PEDI-CAT mobility t-scores compared to controls. There was no difference in MABC between groups. In 11% of cases and 1% of controls, parents reported child mood problems.Children with in utero ZIKV exposure without CZS may demonstrate emerging differences in executive function, mood, and adaptive mobility that require continued evaluation.Preschool neurodevelopmental outcome in children with in utero Zika virus exposure is not yet known, since the Zika virus epidemic occurred in 2015-2017 and these children are only now entering school age. This study finds that Colombian children with in utero Zika virus exposure without congenital Zika syndrome are overall developing well but may have emerging differences in executive function, behavior and mood, and adaptive mobility compared to children without in utero Zika virus exposure. Children with in utero Zika virus exposure require continued multi-domain longitudinal neurodevelopmental evaluation through school age.

This randomized trial compared the first online parent training program for an evidence-supported executive function intervention for autism to in-person parent training with the same dose and content. Parents of autistic children (8–12 years-old; Full Scale IQ above 70) were randomized to in-person ( n = 51) or online ( n = 46) training. Training acceptability and feasibility were rated highly by parents, without significant differences between groups. The completion rate was lower for parents in the online versus the in-person training condition, but neither the total time spent with training materials, nor parent and child outcomes differed by condition. Parents reported that training resulted in a reduction in caregiver strain (Cohen’s d = 0.66) and modest improvements in child flexibility, emotional control and global EF, but not planning and organization. Dose of parent training had a significant positive effect on child planning and organization problems. These findings did not support the hypothesized superiority of online to in-person training, but they did indicate online is as effective as in-person training at helping parents learn to improve their autistic children’s EF abilities and reduce their own experience of parenting strain. Implications included increased access to training for parents who experience barriers to receiving in-person care. Trial Registration: clinicaltrials.gov Identifier: NCT02708069 Lay Abstract This study compared the first online parent training program for executive function intervention for autism to in-person parent training on the same content. Participants were parents of autistic children, who were between 8 and 12 years of age and did not have intellectual disability. Parents were randomized to the in-person ( n = 51) or online ( n = 46) training conditions. Both trainings were developed with stakeholder (parents and autistic people) guidance. In this trial, most parents reported that they liked both trainings and that they were able to implement what they learned with their children. Parents in both groups spent equivalent amounts of time (about 8 hours) with the training materials, but while 94% of parents in the in-person training attended both parent trainings, only 59% of parents in the online group completed all 10 online modules. Parents reported that it was difficult to stay motivated to complete the online trainings over the 10-week trial. Parent and child outcomes did not differ significantly between the groups. Overall, parents reported that the trainings resulted in a reduction in their own parenting strain and improvements in their child’s flexibility, emotional control, and global executive function, but not planning and organization. These findings indicated brief in-person and online training can help parents learn to support and improve their autistic children’s executive function abilities, reducing their own experience of parenting strain. The finding that the online training was equivalent to the in-person trainings is important because it is accessible to parents who encounter barriers to in-person care.

Objectives Vosoritide is a C-type natriuretic peptide analog which binds its receptor on chondrocytes, leading to increased chondrocyte proliferation and differentiation via its inhibition of the ERK1/2-MAPK pathway. It was recently approved for increasing linear growth in children with achondroplasia. Our study aims to assess the safety and efficacy of vosoritide in children with genetic mutations in 6 categories: hypochondroplasia, Rasopathies (including Noonan syndrome), aggrecan deficiency, carriers of heterozygous NPR2 mutations, CNP deficiency, and SHOX deficiency. Methods This is a prospective, Phase II study with a goal N of 35 subjects. All subjects must have a documented genetic mutation in one of the 6 categories, be prepubertal between the ages of 3 and 11 for boys and 3 and 10 for girls, and have a height < -2.25 SD. Subjects are followed for a 6-month observation period to establish a baseline annualized growth velocity (AGV) and then receive daily subcutaneous vosoritide (15 mcg/kg/day) for 12 months. The primary outcomes are rate of AEs and change in AGV from baseline. Pharmacokinetic studies and pharmacodynamic studies, using cGMP production as a pharmacodynamic marker, are completed at Day 1 and Months 6 and 12. Results To date, 27 subjects have enrolled in the trial (20 hypochondroplasia, 3 Noonan, 2 NPR2, 2 Aggrecan). Median baseline height is -3.1 SD (IQR -3.6, -2.6). 14 subjects have initiated on vosoritide, and 10 completed 6 months of therapy. Median increase in AGV was 3.9 cm/yr (IQR 2.2, 4.6). The two subjects with NPR2 mutations had increased AGVs of 4.4 and 9.2 cm/yr. The two subjects with Noonan syndrome had an increase in AGV of 7.5 and 3.3 cm/yr. One subject with Noonan syndrome, a 4-year-old male, had previously been treated with growth hormone (GH) for 2 years. His AGV was 6.7 cm/yr while on GH, 4.1 cm/yr during the 6-month observation period, and 11.6 cm/year during the first 6 months of vosoritide treatment. There were no serious adverse events related to vosoritide treatment. One subject had a brief episode of syncope with her first injection which self-resolved, and she continued on therapy with no further incidents. PK parameters were similar to previously published parameters for vosoritide in children with achondroplasia. In preliminary data, vosoritide Cmax and AUC correlated strongly with peak increase in cGMP (r=0.70, p=0.01;r=0.84, p Conclusions This is the first clinical trial of vosoritide for children with genetic short stature who do not have achondroplasia. Vosoritide treatment may work as a precision therapy to improve growth in multiple genetic conditions which interact with the ERK1/2-MAPK pathway. Presentation: Monday, June 13, 2022 12:00 p.m. - 12:15 p.m.

A wide variety of techniques are used to assess the development of survey-based scales. The majority of these techniques focus on the quality of information characterized by the scale. Aside from very rudimentary measures such as response rates and sample sizes, very few empirical techniques are available to measure the quantity of information contained in a scale. This article conducts an exploratory empirical analysis to assess whether information entropy can be useful for measuring the quantity of information in a scale’s development. If the quantity of information in the scale significantly increases (decreases) with the addition of the survey item, researchers may consider retaining (discarding) that item in the scale. The study was conducted within the context of a natural experiment that occurred at a major amateur sporting event in 2018. Customer satisfaction was assessed using a survey whose core questions have been assessed repeatedly over time. The most recent survey contained a previously validated empathy scale, with two items contained in the base measure. Six additional items were added to this base empathy measure. The quantity of information provided (as measured by information entropy) is calculated for each set of scale items. Statistical analysis indicates that, when adding the behavioral, cognitive, and affective scales to the two-item base scale, the quantity of information available increased. However, most of the increase in information quantity was attributable to three survey items, one item from each of the behavioral, cognitive, and affective domains. These findings suggest that information entropy may indeed be a useful quality control tool for survey scale development.

Purpose This study sought to determine the feasibility of using phonetic complexity manipulations as a way to systematically assess articulatory deficits in talkers with progressive dysarthria due to Parkinson's disease (PD). Method Articulatory kinematics were recorded using three-dimensional electromagnetic articulography from 15 talkers with PD (58–84 years old) and 15 healthy controls (55–80 years old) while they produced target words embedded in a carrier phrase. Majority of the talkers with PD exhibited a relatively mild dysarthria. For stimuli selection, phonetic complexity was calculated for a variety of words using the framework proposed by Kent (1992) , and six words representative of low, medium, and high phonetic complexity were selected as targets. Jaw, posterior tongue, and anterior tongue kinematic measures that were used to test for phonetic complexity effects included movement speed, cumulative path distance, movement range, movement duration, and spatiotemporal variability. Results Significantly smaller movements and slower movement speeds were evident in talkers with PD, predominantly for words with high phonetic complexity. The effect sizes of between-groups differences were larger for several jaw kinematic measures than those of the tongue. Discussion and Conclusion Findings suggest that systematic manipulations of phonetic complexity can support the detection of articulatory deficits in talkers with PD. Phonetic complexity should therefore be leveraged for the assessment of articulatory performance in talkers with progressive dysarthria. Future work will be directed toward linking speech kinematic and auditory–perceptual measures to determine the clinical significance of the current findings.

The pediatric early warning score (PEWS) is a tool used to predict clinical deterioration. Referenced vital sign parameters are based on expert opinion but heart rate and respiratory rate percentiles in hospitalized children have been published. This retrospective case-control study of unplanned intensive care unit (ICU) transfers compares evidence-based vital signs (EBVS) effect on PEWS sensitivity and specificity, determines the impact of age categories on PEWS deterioration prediction, and evaluates whether EBVS PEWS is associated with need for invasive ICU supports. EBVS PEWS improved sensitivity (43%-71% vs 30%-63%) for unplanned transfers with slightly decreased specificity (88%-98% vs 93%-99%). Logistic regression analysis and odds ratios (ORs) demonstrated EBVS PEWS was associated with increased risk for ICU-specific supports (OR = 1.16, 95% confidence interval [CI] = 1.0-1.34, P = .0498). Evidence-based vital signs can improve PEWS sensitivity to identify unplanned ICU transfers and identify patients requiring ICU-specific interventions.

Patients with hematologic malignancies relapsing after allogeneic blood or marrow transplantation (BMT) have limited response to conventional salvage therapies, with an expected 1-year overall survival (OS) of

Fetal electrocardiogram (ECG) waveform analysis along with cardiac time intervals (CTIs) measurements are critical for the management of high-risk pregnancies. Currently, there is no system that can consistently and accurately measure fetal ECG. In this work, we present a new automatic approach to attenuate the maternal ECG in the frequency domain and enhance it with measurable CTIs. First, the coherent components between the maternal ECG and abdominal ECG were identified and subtracted from the latter in the frequency domain. The residual was then converted into the time domain using the inverse Fourier transform to yield the fetal ECG. This process was improved by averaging multiple beats. Two fetal cardiologists, blinded to the method, assessed the quality of fetal ECG based on a grading system and measured the CTIs. We evaluated the fetal ECG quality of our method and time-based methods using one synthetic dataset, one human dataset available in the public domain, and 37 clinical datasets. Among the 37 datasets analyzed, the mean average (± standard deviation) grade was 3.49 ± 1.22 for our method vs. 2.64 ± 1.26 for adaptive interference cancellation (p-value0.001), thus showing the frequency-based fetal ECG extraction was the superior method, as assessed from our clinicians' perspectives. This method has the potential for use in clinical settings.

Optimal management of patients with combined immunodeficiency, especially pertaining to hematopoietic stem cell transplantation (HSCT), remains unclear.To identify factors influencing HSCT and mortality in the population with combined immunodeficiency in North America.We identified 337 participants in the United States Immunodeficiency Network database with diverse forms of combined immunodeficiency and their characteristics, including demographic characteristics, laboratory values, infectious history, comorbidities, and treatment strategies. Univariate analysis was performed using logistic regression, whereas multivariate analysis was performed using multiple Cox proportional hazards.On univariate analysis, disseminated invasive viral infections and variants in STAT3, GATA2, and, DOCK8 were associated with increased odds of HSCT. Mucocutaneous fungal infections and variants in STAT3 were associated with increased odds of survival, whereas disseminated/invasive fungal infections, disseminated/invasive viral infections, and parasitic infections were associated with decreased odds of survival. On multiple variable Cox proportional hazards analysis, variants in ZAP70, nonspecific bacterial, and disseminated/invasive viral infections were associated with increased hazards of transplantation, whereas variants in multiple genes (RMRP, NEMO, DOCK8, CD40L, and CARD9), disseminated/invasive viral infections, autoimmune disease, and higher absolute lymphocyte count were associated with increased hazards of death. Importantly, demographic characteristics, basic lymphocyte subset counts, and absence of genetic diagnosis were not associated with HSCT or mortality.We determined that specific genetic diagnoses and infection burden impacts the decision to undergo HSCT in this cohort. In addition, certain genetic diagnoses and invasive viral infections carry an increased risk of mortality.

Adoptive T cell immunotherapy has been used to restore immunity against multiple viral targets in immunocompromised patients after bone-marrow transplantation and has been proposed as a strategy for preventing coronavirus 2019 (COVID-19) in this population. Ideally, expanded severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-virus-specific T cells (CSTs) should demonstrate marked cell expansion, T cell specificity, and CD8+ T cell skewing prior to adoptive transfer. However, current methodologies using IL-4 + IL-7 result in suboptimal specificity, especially in CD8

Objective:Children with CHD may be at increased risk for epilepsy. While the incidence of perioperative seizures after surgical repair of CHD has been well-described, the incidence of epilepsy is less well-defined. We aim to determine the incidence and predictors of epilepsy in patients with CHD.Methods:Retrospective cohort study of patients with CHD who underwent cardiopulmonary bypass at Results:Two-hundred and twenty-one patients were identified, 157 of whom were included in our analysis. Five patients (3.2%) developed epilepsy. Acute seizures occurred in 12 (7.7%) patients, only one of whom developed epilepsy. Predictors of epilepsy included an earlier gestational age, a lower birth weight, a greater number of cardiac surgeries, a need for extracorporeal membrane oxygenation or a left ventricular assist device, arterial ischaemic stroke, and a longer hospital length of stay.Conclusions:Epilepsy in children with CHD is rare. The mechanism of epileptogenesis in these patients may be the result of a complex interaction of patient-specific factors, some of which may be present even before surgery. Larger long-term follow-up studies are needed to identify risk factors associated with epilepsy in these patients.

To determine the prevalence of and risk factors for cerebral sinus venous thrombosis (CSVT) in neonates undergoing congenital heart disease (CHD) repair.Neonates who had CHD repair with cardiopulmonary bypass and postoperative brain magnetic resonance imaging (MRI) between 2013 and 2019 at a single tertiary care center were identified from institutional databases. Demographic, clinical, and surgical data were abstracted from these databases and from the medical record; 278 neonates with CHD had cardiopulmonary bypass, 184 of whom had a postoperative brain MRI.Eight patients (4.3%) had a CSVT. Transposition of the great arteries with an intact ventricular septum (P .01) and interrupted aortic arch (P = .02) were associated with an increased risk for CSVT. Other risk factors for CSVT included cross-clamp time (98 [IQR, 77.5-120] minutes vs 67 [IQR, 44-102] minutes; P = .03), units of platelets (3.63 [IQR, 3-4] vs 2.17 [IQR, 1-4]; P .01) and packed red blood cells (0.81 [IQR, 0.25-1] vs 1.21 [IQR, 1-1]; P = .03) transfused intraoperatively, and time between surgery and MRI (10 [IQR, 7-12.5] days vs 20 [IQR, 12-35] days; P .01). Five patients (62.5%) were treated with anticoagulation. All patients had complete or partial resolution of their CSVT, regardless of treatment.Brain MRI after cardiopulmonary bypass in neonates revealed a low prevalence of CSVT (4.3%). Further studies are needed to establish best practices for surveillance, prevention, and treatment of CSVT in this population.

Hematopoietic stem cell transplantation (HSCT) can be curative for sickle cell disease (SCD). SCD patients with cerebrovascular disease are often referred for HSCT. The objective of this study was to describe neurologic outcomes after HSCT in patients with pre-existing SCD and cerebrovascular comorbidity. Patients with SCD treated with HSCT at a single center between 1996 and 2019 were identified. Patients with cerebral ischemia and/or vasculopathy before undergoing HSCT were included. Patients with graft failure were excluded. The cohort was divided into 3 groups: symptomatic stroke, vasculopathy without symptomatic stroke, and isolated silent cerebral infarction (SCI). Magnetic resonance imaging/angiography and neurologic assessments pre- and post-HSCT were analyzed to assess outcomes. In a cohort of 44 patients, there were 25 with symptomatic infarction, 10 with vasculopathy, and 9 with isolated SCI. Post-HSCT ischemic injury (2 symptomatic strokes, 2 SCIs) was identified in 4 patients, all with previous symptomatic infarction. Within this group (n = 25), the post-HSCT incidence of subsequent symptomatic infarction was 1.6 events/100 patient-years, and SCIs occurred at a rate of 2.2 events/100 patient-years. No patient had progression of vasculopathy post-HSCT. Our data show a low incidence of new ischemic injury after successful HSCT for SCD. Patients with a history of both symptomatic stroke and vasculopathy are at greatest risk for post-HSCT ischemic injury.

Background This study investigated the clinical implication of TNK2 expression in esophageal cancer patients’ cancer tissue samples. Methods The expression of TNK2 in esophageal cancer tissues and para‐carcinoma tissue was assessed with immunohistochemistry and Western blot analysis; besides, the proteins of CDC42, EGFR, and Akt were also analyzed. Then, Kaplan‐Meier survival curves of TNK2 protein expression level were assayed with 184 esophageal cancer patients from TCGA database. Moreover, with multiple linear regression analysis, we detected the correlations of TNK2 expression associated with tumor differentiation degree and metastasis status. Results It revealed that TNK2 was highly expressed in the cytoplasm of esophageal cancer tissues compared with para‐carcinoma tissue; besides, the proteins of CDC42, EGFR, and Akt were also up‐regulated in different levels of esophageal cancer tissues. However, there was no significant difference of the overall survival time of TNK2 protein expression in 184 esophageal cancer patients from TCGA database (p = 0.37). But, in the included study samples of our study, there was positive coefficience between TNK2 protein expression and differentiation degree in esophageal cancer with multiple linear regression analysis [R = 0.928, 95% confidence interval (0.085‐0.12)]. Conclusion Our results indicated that TNK2 was a potential diagnostic marker and promoted esophageal cancer progression through activating EGFR‐AKT signaling., The dependent linear equation was TNK2=0.103 + 0.042 (differentiation degree) ‐ 0.026 (metastasis status) with Multiple linear regression analysis, the coefficient of regression (R) was 0.928 of differentiation degree, ‐0.25 for status of metastasis, 95% confidence interval (0.085~0.12), p

Objective: To quantify the use of the interprofessional team member (ITM) domain of entrustable professional activities (EPAs) by North Dakota pharmacists across practice sites, roles in practice, and by preceptor status. Methods: Survey methods were used to characterize the self-reported frequency with which pharmacists undertake core EPAs and supporting tasks in the ITM domain. The survey was administered to registered pharmacists practicing in North Dakota (n=990) during the fall of 2018, of which 457 (46.1%) responded. After eliminating responses with incomplete or missing information, 119 responses were available for analysis. Results: For the overall EPA ITM domain, “Collaborate as a member of an interprofessional team population” pharmacists reported performing these activities an average (mean) of 3.3 times per month (SD=2.3). Within this domain, the highest reported example activity was “Use setting appropriate communication skills when interacting with others” (mean=4.1, SD 1.8), followed by “Communicate a patient’s medication-related problem(s) to another health professional” (mean=3.3, SD 2.0), and “Contribute medication-related expertise to the team’s work” (mean=3.1, SD=2.2). ITM domain and supporting example activities were performed at a greater rate in hospitals, community health centers and long-term-care facilities. For most items, preceptors reported a greater use of activities, than did non-preceptors. Conclusions: North Dakota pharmacists currently complete tasks outlined in the ITM domain of the EPAs, although their contributions are varied by task, role, and preceptor status.

Osteogenesis imperfecta (OI) is a genetic connective tissue disorder characterized by compromised skeletal integrity, altered microarchitecture, and bone fragility. Current OI treatment strategies focus on bone antiresorptives and surgical intervention with limited effectiveness, and thus identifying alternative therapeutic options remains critical. Muscle is an important stimulus for bone formation. Myostatin, a TGF-β superfamily myokine, acts through ActRIIB to negatively regulate muscle growth. Recent studies demonstrated the potential benefit of myostatin inhibition with the soluble ActRIIB fusion protein on skeletal properties, although various OI mouse models exhibited variable skeletal responses. The genetic and clinical heterogeneity associated with OI, the lack of specificity of the ActRIIB decoy molecule for myostatin alone, and adverse events in human clinical trials further the need to clarify myostatin's therapeutic potential and role in skeletal integrity. In this study, we determined musculoskeletal outcomes of genetic myostatin deficiency and postnatal pharmacological myostatin inhibition by a monoclonal anti-myostatin antibody (Regn647) in the G610C mouse, a model of mild-moderate type I/IV human OI. In the postnatal study, 5-week-old wild-type and +/G610C male and female littermates were treated with Regn647 or a control antibody for 11 weeks or for 7 weeks followed by a 4-week treatment holiday. Inhibition of myostatin, whether genetically or pharmacologically, increased muscle mass regardless of OI genotype, although to varying degrees. Genetic myostatin deficiency increased hindlimb muscle weights by 6.9% to 34.4%, whereas pharmacological inhibition increased them by 13.5% to 29.6%. Female +/mstn +/G610C (Dbl.Het) mice tended to have similar trabecular and cortical bone parameters as Wt showing reversal of +/G610C characteristics but with minimal effect of +/mstn occurring in male mice. Pharmacologic myostatin inhibition failed to improve skeletal bone properties of male or female +/G610C mice, although skeletal microarchitectural and biomechanical improvements were observed in male wild-type mice. Four-week treatment holiday did not alter skeletal outcomes. © 2020 American Society for Bone and Mineral Research (ASBMR).