Clinician adherence to pharmacogenomics prescribing recommendations in clinical decision support alerts.

Thoughtful integration of interruptive clinical decision support (CDS) alerts within the electronic health record is essential to guide clinicians on the application of pharmacogenomic results at point of care. St. Jude Children's Research Hospital implemented a preemptive pharmacogenomic testing program in 2011 in a multidisciplinary effort involving extensive education to clinicians about pharmacogenomic implications.

Histiocytic Neoplasms, Version 2.2021, NCCN Clinical Practice Guidelines in Oncology.

Histiocytic neoplasms are rare hematologic disorders accounting for less than 1% of cancers of the soft tissue and lymph nodes. Clinical presentation and prognosis of these disorders can be highly variable, leading to challenges for diagnosis and optimal management of these patients. Treatment often consists of systemic therapy, and recent studies support use of targeted therapies for patients with these disorders.

Neuroinflammatory Disease as an Isolated Manifestation of Hemophagocytic Lymphohistiocytosis.

Isolated neuroinflammatory disease has been described in case reports of familial hemophagocytic lymphohistiocytosis (FHL), but the clinical spectrum of disease manifestations, response to therapy and prognosis remain poorly defined. We combined an international survey with a literature search to identify FHL patients with (i) initial presentation with isolated neurological symptoms; (ii) absence of cytopenia and splenomegaly at presentation; and (iii) systemic HLH features no earlier than 3 months after neurological presentation. Thirty-eight (20 unreported) patients were identified with initial diagnoses including acute demyelinating encephalopathy, leukoencephalopathy, CNS vasculitis, multiple sclerosis, and encephalitis.

Dasatinib induces a dramatic response in a child with refractory juvenile xanthogranuloma with a novel MRC1-PDGFRB fusion.

Juvenile xanthogranuloma (JXG) usually presents with lesions isolated to the skin; however, aggressive, disseminated forms also occur. Identification of a novel fusion in a child with JXG guided targeted therapy with dasatinib, leading to a dramatic response.

Optimizing Drug-Drug Interaction Alerts Using a Multidimensional Approach.

Objectives: Excessive alerts are a common concern associated with clinical decision support systems that monitor drug-drug interactions (DDIs). To reduce the number of low-value interruptive DDI alerts at our hospital, we implemented an iterative, multidimensional quality improvement effort, which included an interdisciplinary advisory group, alert metrics, and measurement of perceived clinical value.

Methods: Alert data analysis indicated that DDIs were the most common interruptive medication alert.

Pentamidine for Prophylaxis against Pneumocystis jirovecii Pneumonia in Pediatric Oncology Patients Receiving Immunosuppressive Chemotherapy.

pneumonia is a life-threatening opportunistic infection in children receiving immunosuppressive chemotherapy. Without prophylaxis, up to 25% of pediatric oncology patients receiving chemotherapy will develop pneumonia. Trimethoprim-sulfamethoxazole is the preferred agent for prophylaxis against pneumonia.

Clofarabine salvage therapy for refractory high-risk langerhans cell histiocytosis.

Pediatric patients with refractory multisystem Langerhans cell histiocytosis (LCH) have a poor prognosis despite aggressive chemotherapy. Salvage therapy with cytarabine and cladribine has shown promise as an effective treatment but is associated with significant toxicity. A previous report described two patients with refractory LCH who had a rapid response to single-agent clofarabine with minimal toxicity.

Identification of a novel, tissue-specific ABCG2 promoter expressed in pediatric acute megakaryoblastic leukemia.

ABCG2 encodes a transporter protein that is associated with multidrug-resistant phenotypes in many cancers, including acute myeloid leukemia (AML); high levels of expression are generally associated with a poor prognosis. To better understand how expression of ABCG2 is controlled in pediatric AML, we performed a detailed analysis of the ABCG2 transcript isoforms from a variety of tissue sources, including 85 pediatric AML samples. These studies revealed a complex 5' untranslated region (UTR) with 6 novel exons and multiple splice variants.

Application of a new hydrogel dural sealant that reduces epidural adhesion formation: evaluation in a large animal laminectomy model.

Object: The aim of this study was to evaluate the application and effects of a novel, nonswelling, polyethylene glycol-based hydrogel adhesion barrier and sealant in a canine laminectomy model of CSF leakage and adhesion formation.

Methods: After full-width L-2 and L-5 laminectomies, 1-cm midline durotomies were created and sutured closed, except for the last 1-2 mm on the cranial end to create spontaneous CSF leakage. All 5 control animals received no further treatment.

Pre-clinical evaluation of a next-generation spray adhesion barrier for multiple site adhesion protection.

Intra-abdominal adhesions represent a major cause of postoperative morbidity, including chronic or recurrent pelvic pain and infertility in a significant percent of patients. The SprayShield™ Adhesion Barrier System (Covidien, Waltham, MA) is a next-generation sprayable adhesion barrier to prevent postoperative adhesions. Initially sprayed as a liquid, SprayShield™ solidifies within 2 seconds of contact with tissue through a polyethylene glycol (PEG) ester-Trilysine reaction to form an adherent, internal tissue barrier that protects the underlying tissues for several days after surgery.

Application of a hydrogel sealant improves watertight closures of duraplasty onlay grafts in a canine craniotomy model.

Object: The authors evaluated whether a polyethylene glycol-based hydrogel sealant system improved dural closures with collagen-based duraplasty onlay grafts.

Methods: Dural defects 1.5 cm in diameter were created in 12 canines and repaired with one of two commercially available duraplasty onlay products.

Loss of alpha-tubulin polyglutamylation in ROSA22 mice is associated with abnormal targeting of KIF1A and modulated synaptic function.

Microtubules function as molecular tracks along which motor proteins transport a variety of cargo to discrete destinations within the cell. The carboxyl termini of alpha- and beta-tubulin can undergo different posttranslational modifications, including polyglutamylation, which is particularly abundant within the mammalian nervous system. Thus, this modification could serve as a molecular "traffic sign" for motor proteins in neuronal cells.

DuraSeal magnetic resonance and computed tomography imaging: evaluation in a canine craniotomy model.

Objective: Several novel sealing materials have been proposed as an adjunct to sutured dural closure to help insure watertight closure, thus diminishing the risk of pseudomeningocele formation. This evaluation was undertaken to clarify the in vivo magnetic resonance imaging (MRI) and computed tomographic (CT) scan characteristics of one such sealant, which has a high water content, permitting similar imaging characteristics to pseudomeningoceles and inflammatory collections.

Methods: After a craniotomy in two canine subjects, we sprayed a novel, water-soluble, self-polymerizing, absorbable, hydrogel sealant onto the dura and the bone flap was replaced.

Mutation of a novel gene results in abnormal development of spermatid flagella, loss of intermale aggression and reduced body fat in mice.

ROSA22 male mice are sterile due to a recessive gene-trap mutation that affects development of the spermatid flagellum. The defect involves the flagellar axoneme, which becomes unstable around the time of its assembly. Despite a subsequent complete failure in flagellar assembly, development of the spermatid head appears normal and the spermatid head is released at the correct stage in spermatogenesis.