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A randomized trial of transfusion therapy versus standard therapy showed a reduction in cerebral infarcts among children with sickle cell anemia whose hemoglobin S levels were kept below 30%. Transfusion risks seem to be outweighed by the neurologic benefits. Sickle cell anemia affects 1 of every 396 1 black newborns and approximately 100,000 persons in the United States. 2 , 3 Among children with sickle cell anemia (defined as homozygous hemoglobin S or hemoglobin S-β 0 thalassemia), silent cerebral infarcts are the most common neurologic injury. 4 In contrast to overt stroke (hereinafter referred to as stroke), a silent cerebral infarct is not associated with obvious neurologic impairment and cannot be detected on neurologic examination. 5 However, children with a silent cerebral infarct are at increased risk for stroke, new or enlarged silent cerebral infarcts, 6 poor academic achievement, 7 and lower IQ, as compared either with . . .

Key Clinical Message COVID‐19 psychosis is a potential long‐term sequela of COVID‐19. Vulnerable populations, such as individuals with sickle cell disease, are at high risk for psychosis. Given the limited number of cases, more investigations in the etiopathology and management of this new disease is needed. We report a case of a 15‐year‐old female with a past medical history of depression who developed psychosis post‐SARS‐CoV‐2 infection (COVID‐19). After an initial moderate COVID‐19 infection, the patient appeared to recover and was discharged home. Four weeks later, she presented with symptoms of psychosis and symptoms of cognitive impairment. Imaging studies did not show any evidence of stroke and toxicology studies were negative. She was treated with antipsychotics and required inpatient neuropsychiatric rehabilitation. Acute psychotic syndrome resolved after 3 weeks, antipsychotics were weaned, and an antidepressant was initiated. Mild cognitive impairment with significant memory loss persisted for about 1 year. Thereafter, she returned to her baseline but remains on an antidepressant. Some studies have previously reported the occurrence of psychosis in individuals with COVID‐19. This report is the first outline of severe prolonged post‐COVID‐19 psychosis in a child with sickle cell disease. Given the neurologic vulnerability of children with sickle cell disease, these individuals should be monitored for neuropsychiatric symptoms post COVID‐19.

Background Stroke risk screening using transcranial Doppler (TCD) is a critical evidence-based tool for children with sickle cell anemia (SCA) that has been poorly implemented in the United States. The Dissemination and Implementation of Stroke Prevention Looking at the Care Environment (DISPLACE) study was designed to improve rates of stroke risk screening for SCA using interventions informed by an extensive multi-level barriers and facilitators assessment. This report describes the final outcomes of a large, randomized implementation trial comparing two intervention arms: 1) an application designed to track TCD implementation, ProviderMinder™, versus 2) ProviderMinder™ plus a single coordinator intervention. All sites additionally received a rebranding and educational intervention. The primary outcome was the difference in stroke risk screening rates between intervention arms. The intervention group was compared to four sites that did not implement either intervention and to their baseline rates as secondary outcomes. Methods The initial part of DISPLACE included 28 sites from which 16 sites with poor stroke risk screening implementation were included in the trial and randomized to intervention arms. All sites entered patient data into a secure, customized electronic database and were required to use ProviderMinder™ for stroke risk screening data entry. Three sites were unable to adopt ProviderMinder™ and a fourth site from the original DISPLACE cohort was added to this group, resulting in thirteen intervention sites and four non-implementing sites (NIS). NIS collected data retrospectively for the same period as the implementation trial. A generalized quasi-likelihood Poisson mixed effects regression model compared screening rates between groups and timepoints while controlling for baseline screening rates and site size. Unadjusted stroke risk screening rates were also compared via two-proportion Z-tests for all outcomes. Results The intervention-by-timepoint interaction indicated statistically significant improvement for the ProviderMinder™ arm relative to the combined intervention arm (difference of 10.0%) and for the intervention group (both arms) compared to NIS (difference of 15.9%). Screening rates increased by 28.0% from baseline to intervention, with an overall rate of 76.8%. Conclusions Our intervention approach in DISPLACE significantly improved stroke risk screening for children with SCA, with procedure-patient tracking emerging as an important component for improving care. Trial registration Clinical trial number: ClinicalTrials.gov; NCT04173026; 6/4/2020; https://clinicaltrials.gov/study/NCT04173026?cond=NCT04173026&rank=1

Youth with sickle cell disease (SCD), a genetic disorder of red blood cells, may experience acute pain episodes lasting 2 to 3 days on average. While existing research has demonstrated associations between SCD pain and poor social functioning in youth with SCD, there are no data on whether symptoms of depression and anxiety modify the relationship between pain and functional outcomes in pediatric pain populations. It was hypothesized that more symptoms of depression and anxiety would exacerbate the relationship between high pain and poor social functioning in youth with SCD. We conducted a cross-sectional study of 114 youth with SCD and their guardians assessing the youth's pain, social functioning, and symptoms of depression and anxiety. Analyses indicated that elevated levels of depressive symptoms were related to poorer self-reported interpersonal skills. More anxiety symptoms were related to better guardian-reported social skills and weakened the relationship between high pain frequency and poor self-reported interpersonal skills. Findings build on previous work supporting the need for multidisciplinary approaches to care for youth with SCD who experience pain, and provide rationale for future studies to investigate the direct and possible moderating effects of depression and anxiety symptoms on other functional outcomes in youth with SCD and other pediatric pain populations.

The Signal Transducer and Activator of Transcription (STAT) proteins comprise a family of latent transcription factors with diverse functions. STAT3 has well established roles in cell proliferation, growth and survival, and its persistent activation has been detected with high frequency in many human cancers. As constitutive activation of STAT3 appears to be vital for the continued survival of these cancerous cells, it has emerged as an attractive target for chemotherapeutics. We examined whether the inhibitory activities of bioactive compounds from cruciferous vegetables, such as Benzyl isothiocyanate (BITC) and sulforaphane, extended to STAT3 activation in PANC-1 human pancreatic cancer cells. BITC and sulforaphane were both capable of inhibiting cell viability and inducing apoptosis in PANC-1. Sulforaphane had minimal effect on the direct inhibition of STAT3 tyrosine phosphorylation, however, suggesting its inhibitory activities are most likely STAT3-independent. Conversely, BITC was shown to inhibit the tyrosine phosphorylation of STAT3, but not the phosphorylation of ERK1/2, MAPK and p70S6 kinase. These results suggest that STAT3 may be one of the targets of BITC-mediated inhibition of cell viability in PANC-1 cancer cells. In addition, we show that BITC can prevent the induction of STAT3 activation by Interleukin-6 in MDA-MB-453 breast cancer cells. Furthermore, combinations of BITC and sulforaphane inhibited cell viability and STAT3 phosphorylation more dramatically than either agent alone. These findings suggest that the combination of the dietary agents BITC and sulforaphane has potent inhibitory activity in pancreatic cancer cells and that they may have translational potential as chemopreventative or therapeutic agents.