Anticoagulation for Septic Cerebral Venous Thrombosis in Childhood.

Anticoagulation is recommended for most children with cerebral venous thrombosis (CVT) to prevent venous infarction and promote recanalization. An exception is CVT associated with head and neck infection (septic CVT), for which treatment of infection without concomitant use of anticoagulation is recommended. Despite this, the use of anticoagulation in septic CVT is controversial, and children with septic CVT are often anticoagulated due to concerns about thrombus progression and persistence despite infection treatment. A retrospective study of children with septic CVT cared for at Seattle Children's Hospital between 2009 and 2023 was conducted to assess the safety and outcome of anticoagulation. Among 40 children with septic CVT, 25 (63%) received anticoagulation. None had bleeding complications. Performance of follow-up venous imaging was inconsistent and more commonly pursued in patients treated with anticoagulation. A total of 23/40 (58%) patients were evaluable at 1 month, among whom 26% (6/23) had resolution of thrombus and 74% (17/23) had persistence. A total of 22/40 (55%) patients were evaluable at 3 months, among whom 77% (17/22) had resolution of thrombus and 23% (5/22) had persistence. This supports the safety of anticoagulation, but further studies are needed to determine whether anticoagulation improves outcomes after septic CVT.

Cow's Milk Anemia in Childhood Manifesting as Severe Cerebral Venous Sinus Thrombosis.

We describe a series of 7 toddler-aged children with iron deficiency anemia from excessive cow's milk consumption who presented with cerebral venous sinus thrombosis and no other identifiable risk factors for thrombosis. The deep venous system was involved in 6 patients, 6 had venous infarcts, and 5 have significant neurocognitive sequelae.

Thrombophilia screening in the routine clinical care of children with arterial ischemic stroke.

BACKGROUND: Current guidelines recommend thrombophilia evaluation in childhood arterial ischemic stroke, but the impact of screening on management is unknown. The objective of the current study is to report the incidence of thrombophilia identified as part of routine clinical care in the context of available literature reports, and to describe the impact of a diagnosis of thrombophilia on patient management. METHODS: We conducted a single-institution retrospective chart review for all children with arterial ischemic stroke occurring between January 1, 2009 and January 1, 2021. We collected thrombophilia screening results, stroke etiology, and management. We also reviewed the literature of thrombophilia testing in childhood arterial ischemic stroke published prior to June 30, 2022. Meta-analysis methods were used to assess prevalence rates. RESULTS: Among children with thrombophilia testing performed, 5% (six of 122 patients) were factor V Leiden heterozygous, 1% (one of 102 patients) were prothrombin gene mutation heterozygous, 1% (one of 122) had protein S deficiency, 20% (23/116 patients) had elevated lipoprotein(a), 3% (three of 110 patients) had elevated homocysteine levels, and 9% (10/112) had elevated antiphospholipid antibodies, only two of whom had persistently elevated levels. There was no change in stroke therapy due to these results. Literature review revealed a wide range of prevalence for most thrombophilia traits, with high cross-study heterogeneity in most cases. CONCLUSIONS: The rates of thrombophilia in our cohort were consistent with that expected in the general population. The identification of thrombophilia did not alter stroke care. However, some of the results were actionable, prompting evaluation for lipid disorders and patient-specific counseling on cardiovascular risk and risk for venous thrombosis.

Management of Contraception in Adolescent Females With Hormone-Related Venous Thromboembolism.

PURPOSE: Management of contraception in adolescent females with hormone-related venous thromboembolism (VTE) is challenging. We examined the characteristics of this patient population and outcomes, including recurrent VTE, heavy menstrual bleeding, and pregnancy. METHODS: We performed a single-institution retrospective cohort study of adolescents with a new diagnosis of VTE and concurrent use of estrogen- and/or progestin-containing medication (N = 89). We collected data on additional risk factors for thrombosis, management of hormone therapy, and anticoagulation. We compared outcomes between patients with prescribed contraception within the year after their VTE diagnosis (n = 52) with those without (n = 37). RESULTS: At least one additional risk factor for thrombosis was identified in 92% of patients, and 73% had two or more. The most common additional thrombosis risk factors were obesity (35%), family history (33%), and recent immobility (33%). Ninety-seven percent of patients were receiving combined hormonal medications, and 42% of patients had their medication stopped and not replaced with an alternative. Heavy menstrual bleeding was reported while on anticoagulation in 46% of patients with a documented menstrual history. Recurrent VTE occurred in 9.0% of patients. The group without prescribed contraception had a significantly higher rate of pregnancy in the two years after VTE diagnosis (18% vs. 1.9%, p = .04). Two pregnancies occurred while on warfarin. DISCUSSION: Early assessment of contraceptive needs and menstrual bleeding symptoms are needed after diagnosis of hormone-related VTE in adolescent females. Access to contraceptive methods associated with low thrombosis risk is important for the prevention of unplanned pregnancy in this patient population.

Risk factors for neutropenia in clozapine-treated children and adolescents with childhood-onset schizophrenia.

OBJECTIVE: The purpose of this study was to retrospectively analyze rates of neutropenia and risk factors for neutropenia in hospitalized children and adolescents treated with clozapine. METHODS: A retrospective chart review was conducted for all patients who received clozapine at any time during a hospitalization at the National Institute of Mental Health (NIMH) between 1990 and 2011. All patients satisfied screening criteria for the NIMH childhood-onset schizophrenia study, including onset of psychosis before the age of 13 years. Absolute neutrophil count (ANC) values recorded during inpatient hospitalization were extracted for 87 eligible patients with a mean age of 13.35±2.46 years at hospitalization and a mean length of stay of 117±43 days. RESULTS: Mild neutropenia only (lowest ANC<2000/mm3 but>1500/mm3) was observed in 27 (31%) patients and moderate neutropenia (any ANC<1500/mm3) was observed in 17 (20%) patients. There were no cases of agranulocytosis or severe infection. Significant risk factors for mild neutropenia compared with no hematologic adverse effects (HAEs) were male gender (p=0.012) and younger age (p<0.001). Male gender was also a significant risk factor for moderate neutropenia compared with no HAEs (p=0.003). If a child of African American ethnicity developed neutropenia during hospitalization at all that child was significantly more likely to develop moderate neutropenia than mild neutropenia only (p=0.017). African American boys had the highest rate of moderate neutropenia at 47%. Sixteen of the 17 patients exhibiting moderate neutropenia were successfully treated with clozapine by the time of discharge; 8 of these 16 required adjunctive lithium carbonate administration to maintain ANC>2000/mm3. CONCLUSIONS: Our study shows that the rates of neutropenia in clozapine-treated children and adolescents are considerably higher than in the adult population. Younger age, African American ethnicity, and male gender were significant risk factors. These are also risk factors for benign neutropenia in healthy children and adolescents. Despite these high rates of neutropenia, all but one of the patients with neutropenia during hospitalization were successfully discharged on clozapine.

Electrically driven light emission from individual CdSe nanowires.

We report electroluminescence (EL) measurements carried out on three-terminal devices incorporating individual n-type CdSe nanowires. Simultaneous optical and electrical measurements reveal that EL occurs near the contact between the nanowire and a positively biased electrode or drain. The surface potential profile, obtained by using Kelvin probe microscopy, shows an abrupt potential drop near the position of the EL spot, while the band profile obtained from scanning photocurrent microscopy indicates the existence of an n-type Schottky barrier at the interface. These observations indicate that light emission occurs through a hole leakage or an inelastic scattering induced by the rapid potential drop at the nanowire-electrode interface.

Catalyst-assisted solution-liquid-solid synthesis of CdS/CdSe nanorod heterostructures.

We report the synthesis and characterization of axial nanorod heterostructures composed of cadmium selenide (CdSe) and cadmium sulfide (CdS). The synthesis employs a solution-liquid-solid (SLS) mechanism with the assistance of bismuth nanocrystals adhered to a substrate (silicon or a III-V semiconductor). Transmission electron microscopy (TEM) and diffraction studies show that CdSe and CdS segments exhibit the wurtzite (hexagonal) crystal structure with <5% stacking faults. Both of these segments grow along the [002] direction with an epitaxial interface between them. Energy-dispersive X-ray (EDX) spectrometry using a high-resolution TEM operating in scanning mode confirms the alloy-free composition modulation in the nanorod heterostructures, showing that Se and S are localized in the CdSe and CdS portions of the nanorod heterostructures, respectively. This study demonstrates that SLS synthesis provides an alternate route to prepare axial nanorod heterostructures that have been difficult to generate using either vapor-liquid-solid growth or catalyst-free solution-phase synthesis.

Electroluminescence from a single-nanocrystal transistor.

We report the fabrication and characterization of light-emitting transistors incorporating individual cadmium selenide (CdSe) nanocrystals. Electrical measurements conducted at low bias voltage and low temperature show clear evidence of Coulomb blockade behavior, indicating that electrons pass through the nanocrystal by single-electron tunneling. Once the bias voltage exceeds the band gap of CdSe, devices with asymmetric tunnel barriers emit linearly polarized light. Combined analyses of the electrical and optical data indicate that the tunnel couplings between the nanorod and the metallic electrodes change significantly as a function of bias voltage and light emission results from the inelastic scattering of tunneling electrons.