Neuromodulation of the Cerebellum for Motor Applications: A Systematic Review.

Background: Despite the connections and clear importance of the cerebellum in motor function, research utilizing cerebellar neuromodulation for treatment of movement disorders is still underdeveloped. Here we conduct a systematic review to investigate non-invasive neurostimulation of the cerebellum and its potential impact on motor systems and its function. Our aim is to give a general review of each neurostimulation study focusing on the cerebellum as a treatment target in the past five years at time of search, in order to update the field on current findings and inspire similar cerebellar neurostimulation research without unnecessary repetition.

Switching from Sucrose-Formulated rFVIII to Octocog Alfa (BAY 81-8973) Prophylaxis Improves Bleed Outcomes in the LEOPOLD Clinical Trials.

Introduction: Previous clinical trials established the efficacy and safety of sucrose-formulated recombinant factor (F) VIII (rFVIII-FS/Kogenate FS®/Helixate FS®) and octocog alfa (BAY 81-8973/Kovaltry®; LEOPOLD trials).

Aim: To report the results of a post hoc subgroup analysis assessing efficacy and safety outcomes in patients with hemophilia A who were receiving rFVIII-FS prior to enrolling into the LEOPOLD I Part B and LEOPOLD Kids Part A clinical trials and switching to octocog alfa.

Methods: LEOPOLD I Part B (NCT01029340) and LEOPOLD Kids Part A (NCT01311648) were octocog alfa Phase 3, multinational, open-label studies in patients with severe hemophilia A aged 12-65 years and ≤12 years, respectively.

Design and Usability of an Electronic Health Record-Integrated, Point-of-Care, Clinical Decision Support Tool for Modeling and Simulation of Antihemophilic Factors.

Background: With the consequences of inadequate dosing ranging from increased bleeding risk to excessive drug costs and undesirable administration regimens, the antihemophilic factors are uniquely suited to dose individualization. However, existing options for individualization are limited and exist outside the flow of care. We developed clinical decision support (CDS) software that is integrated with our electronic health record (EHR) and designed to streamline the process for our hematology providers.

Awareness, Care and Treatment In Obesity maNagement to inform Haemophilia Obesity Patient Empowerment (ACTION-TO-HOPE): Results of a survey of US patients with haemophilia and obesity (PwHO) and their partners and caregivers.

Background: The ACTION study identified barriers to initiating and maintaining weight loss in patients with obesity; however, joint-related issues (pain, mobility and bleeding) may affect perceptions of patients with haemophilia and obesity (PwHO).

Aim: To identify patient and caregiver insights on the unique challenges of PwHO.

Methods: Following IRB approval, adults who self-identified as PwHO, spouses/partners of adult PwHO, and caregivers of adolescent PwHO (aged 12-17 years) completed an online survey between December 2017 and April 2018.

Hereditary spherocytosis: a risk factor for thigh pressure myonecrosis in posterior spine surgery.

The objective of this study was to make surgeons aware of a potential pressure complication in posterior spine surgery for patients with hereditary spherocytosis (HS) and to present a plausible hypothesis for injury. Posterior spine surgery is common practice for adolescent idiopathic scoliosis (AIS). Common, less severe surgical risks include pressure ulcers; while rare, more severe pressure complications include rhabdomyolysis and compartment syndrome.

The impact of thromboelastography on resuscitation in pediatric liver transplantation.

Although TEG directs effective resuscitation in adult surgical patients, pediatric data are lacking. We performed a retrospective comparative review of the effect of TEG on blood product utilization and outcomes following pediatric liver transplantation in 38 patients between 2008 and 2014. Diagnoses, laboratory values, fluid and blood product use, and outcomes were examined.

Limit of detection and threshold for positivity of the Centers for Disease Control and Prevention assay for factor VIII inhibitors.

Unlabelled: Essentials Immunologic methods detect factor VIII (FVIII) antibodies in some inhibitor-negative specimens. Specimens were tested by modified Nijmegen-Bethesda assay (NBA) and fluorescence immunoassay. The NBA with preanalytical heat inactivation detects FVIII inhibitors down to 0.

A Randomized Trial of Factor VIII and Neutralizing Antibodies in Hemophilia A.

Background: The development of neutralizing anti-factor VIII alloantibodies (inhibitors) in patients with severe hemophilia A may depend on the concentrate used for replacement therapy.

Methods: We conducted a randomized trial to assess the incidence of factor VIII inhibitors among patients treated with plasma-derived factor VIII containing von Willebrand factor or recombinant factor VIII. Patients who met the eligibility criteria (male sex, age <6 years, severe hemophilia A, and no previous treatment with any factor VIII concentrate or only minimal treatment with blood components) were included from 42 sites.

Prophylactic versus reactive transfusion of thawed plasma in patients undergoing surgical repair of craniosynostosis: a randomized clinical trial.

Background: Surgical repair of craniosynostosis in young children is associated with copious bleeding and often coagulopathy. Typically, a reactive transfusion strategy is used to treat coagulopathy whereby fresh frozen plasma (FFP) is given only after clinical manifestation of clotting abnormality. This prospective, randomized clinical trial was designed to test the hypothesis that prophylactic FFP during craniofacial surgery reduces blood loss and blood transfusion requirements compared to a reactive FFP transfusion strategy.

Hepatitis B vaccination is effective by subcutaneous route in children with bleeding disorders: a universal data collection database analysis.

Subcutaneous (SQ) vs. intramuscular (IM) vaccination may cause fewer injection site complications in children with bleeding disorders, but little is known about comparative immunogenicity. To compare immunogenicity of hepatitis B virus (HBV) vaccination administered SQ or IM to individuals <2 years old with bleeding disorders, we performed a retrospective analysis of HBV surface antibody titres among patients enrolled in the universal data collection database who had received three doses of HBV vaccine solely by one route (SQ or IM).

Comparison of clot-based, chromogenic and fluorescence assays for measurement of factor VIII inhibitors in the US Hemophilia Inhibitor Research Study.

Background: Detection and validation of inhibitors (antibodies) to hemophilia treatment products are important for clinical care, evaluation of product safety and assessment of population trends.

Methods: Centralized monitoring for factor VIII (FVIII) inhibitors was conducted for patients in the Hemophilia Inhibitor Research Study using a previously reported modified Nijmegen-Bethesda clotting assay (NBA), a chromogenic Bethesda assay (CBA) and a novel fluorescence immunoassay (FLI).

Results: NBA and CBA were performed on 1005 specimens and FLI on 272 specimens.

Use of pharmacokinetic modelling to individualize FFP dosing in factor V deficiency.

Therapy with fresh frozen plasma (FFP) confers serious risks, such as contraction of blood-borne viruses, allergic reaction, volume overload and development of alloantibodies. The aim of this study was to apply principles of pharmacokinetic (PK) modelling to individual factor content of FFP to optimize individualized dosing, while minimizing potential risks of therapy. We used PK modelling to successfully target individual factor replacement in an 8-month-old patient receiving FFP for treatment of a severe congenital factor V (FV) deficiency.

Bleeding and clotting disorders in pediatric liver disease.

The coagulopathy of liver disease in pediatric patients presents an unusual set of challenges. Little pediatric data have been published, so this review is based largely on adult studies. There is a precarious balance between deficiencies of clotting factors and anticoagulation factors in liver disease that result in abnormal prothrombin time (PT) and activated partial thromboplastin time (aPTT) tests that would suggest a bleeding tendency, yet the patients can form a clot and are at risk of thromboembolic disease.

The use of a single von Willebrand factor-containing, plasma-derived FVIII product in hemophilia A immune tolerance induction: the US experience.

Background: Inhibitors are a serious complication for patients with severe hemophilia A. Immune tolerance induction (ITI) is the primary method for eradicating these inhibitors. The role of type of concentrate and in particular the use of von Willebrand factor-containing, plasma-derived factor VIII (VWF/pd-FVIII) concentrate in primary or rescue ITI remains unclear.

Off-label use of rFVIIa in children with excessive bleeding: a consecutive study of 153 off-label uses in 139 children.

Background: Recombinant factor VIIa is a general hemostatic agent. Randomized trials have demonstrated effectiveness in adults; however, data in children are confined to case reports and series subject to publication bias.

Procedures: A consecutive cohort of children treated with rFVIIa was identified via inspection of pharmacy records.

Prosthetic metals impair murine immune response and cytokine release in vivo and in vitro.

This study was designed to investigate whether prosthetic metals adversely affect immune responses and the release of immunoregulatory cytokines in vivo and in vitro. Titanium and cobalt-chromium alloy were injected into the peritoneal cavity of female mice. At 5, 8, and 12 weeks after the injection, the levels of cobalt and chromium in the blood were significantly increased compared with the levels in control mice; the level of titanium was not significantly changed until 12 weeks.

Prosthetic metals interfere with the functions of human osteoblast cells in vitro.

The release of metals from total joint prostheses may contribute to periprosthetic bone loss manifested as osteolysis. The effects of titanium, cobalt, and chromium on human osteogenic sarcoma cells (osteoblastlike cells) were investigated in vitro. Titanium, cobalt, and chromium at concentrations of 1, 10, and 100 ng/ml did not cause any changes in the cell growth, viability, and injury after 72-hour incubation with the cells.

Titanium, chromium and cobalt ions modulate the release of bone-associated cytokines by human monocytes/macrophages in vitro.

Osteolysis has become a major cause of aseptic loosening in total joint arthroplasty (TJA). Titanium, cobalt and chromium are commonly used in orthopaedic implants (e.g.

Inhibition of T and B cell proliferation by titanium, cobalt, and chromium: role of IL-2 and IL-6.

The mechanism by which an increased risk of prosthetic infection is induced in patients with total joint arthroplasties is poorly understood. The adverse effects of metallic corrosion products of a prosthesis on host defense mechanisms, particularly immune response and release of immunoregulatory cytokines, remain largely unknown. Titanium, cobalt, and chromium are the materials most often used for joint implantation.

Agrobacterium radiobacter: a recently recognized opportunistic pathogen.

Over the past decade, an increasing number of infections due to Agrobacterium radiobacter have been reported. Observation of three cases of bacteremia due to this organism prompted a review of the English-language literature. Nineteen cases of significant disease have previously been reported.