Role of Wrist Arthroscopy in Juvenile Inflammatory Arthritis.

 The wrist is the fourth most common joint to be involved in juvenile inflammatory arthritis (JIA), which is a common rheumatological condition affecting children. Wrist arthroscopy is well established in rheumatoid arthritis, but remains unexplored in JIA. The aim of this study is to investigate the role of wrist arthroscopy in JIA, with focus on those who are refractory to medical management.

Increased incidence of hematologic malignancies in SCD after HCT in adults with graft failure and mixed chimerism.

Lawal et al report on a 45-fold increase in secondary hematologic malignancy in 120 patients following hematopoietic stem cell transplantation (HSCT) for sickle cell disease (SCD), comparable to what has been reported following gene therapy. Notably, the cohort is enriched for older patients and for haploidentical transplant recipients with mixed chimerism following HSCT. These data further support the idea that pre-existing premalignant myeloid clones undergo clonal selection in the setting of nonmyeloablative HSCT and contribute to secondary malignancy.

Juvenile Dermatomyositis Magnetic Resonance Imaging Score (JIS) does not correlate with criteria for clinically inactive disease: a single-centre retrospective evaluation.

The Paediatric Rheumatology International Trials Organisation (PRINTO) criteria for clinically inactive disease (CID) and their proposal for glucocorticoid tapering do not consider MRI findings, despite the growing use of MRI and development of reliable MRI scoring tools. We aim to evaluate how CID correlates with MRI scores and physician decision making. We retrospectively used the Juvenile Dermatomyositis Imaging Score (JIS) to score MRIs of all children with JDM over a 10-year period.

Cyclophosphamide improves engraftment in patients with SCD and severe organ damage who undergo haploidentical PBSCT.

Peripheral blood stem cell transplantation (PBSCT) offers a curative option for sickle cell disease (SCD). Although HLA-matched sibling transplantation is promising, the vast majority of patients lack such a donor. We sought to develop a novel nonmyeloablative HLA-haploidentical PBSCT approach that could safely be used for patients with severe organ damage.

At least 20% donor myeloid chimerism is necessary to reverse the sickle phenotype after allogeneic HSCT.

Novel curative therapies using genetic transfer of normal globin-producing genes into autologous hematopoietic stem cells (HSCs) are in clinical trials for patients with sickle cell disease (SCD). The percentage of transferred globin necessary to cure SCD is currently not known. In the setting of allogeneic nonmyeloablative HSC transplants (HSCTs), stable mixed chimerism is sufficient to reverse the disease.

Hydroxyurea-Increased Fetal Hemoglobin Is Associated with Less Organ Damage and Longer Survival in Adults with Sickle Cell Anemia.

Background: Adults with sickle cell anemia (HbSS) are inconsistently treated with hydroxyurea.

Objectives: We retrospectively evaluated the effects of elevating fetal hemoglobin with hydroxyurea on organ damage and survival in patients enrolled in our screening study between 2001 and 2010.

Methods: An electronic medical record facilitated development of a database for comparison of study parameters based on hydroxyurea exposure and dose.

Gravitational waves from binary supermassive black holes missing in pulsar observations.

Gravitational waves are expected to be radiated by supermassive black hole binaries formed during galaxy mergers. A stochastic superposition of gravitational waves from all such binary systems would modulate the arrival times of pulses from radio pulsars. Using observations of millisecond pulsars obtained with the Parkes radio telescope, we constrained the characteristic amplitude of this background, A(c,yr), to be <1.

Nonmyeloablative HLA-matched sibling allogeneic hematopoietic stem cell transplantation for severe sickle cell phenotype.

Importance: Myeloablative allogeneic hematopoietic stem cell transplantation (HSCT) is curative for children with severe sickle cell disease, but toxicity may be prohibitive for adults. Nonmyeloablative transplantation has been attempted with degrees of preparative regimen intensity, but graft rejection and graft-vs-host disease remain significant.

Objective: To determine the efficacy, safety, and outcome on end-organ function with this low-intensity regimen for sickle cell phenotype with or without thalassemia.

Gravitational-wave limits from pulsar timing constrain supermassive black hole evolution.

The formation and growth processes of supermassive black holes (SMBHs) are not well constrained. SMBH population models, however, provide specific predictions for the properties of the gravitational-wave background (GWB) from binary SMBHs in merging galaxies throughout the universe. Using observations from the Parkes Pulsar Timing Array, we constrain the fractional GWB energy density (Ω(GW)) with 95% confidence to be Ω(GW)(H0/73 kilometers per second per megaparsec)(2) < 1.

Infusion of hemolyzed red blood cells within peripheral blood stem cell grafts in patients with and without sickle cell disease.

Peripheral blood stem cell (PBSC) infusions are associated with complications such as elevated blood pressure and decreased creatinine clearance. Patients with sickle cell disease experience similar manifestations, and some have postulated release of plasma-free hemoglobin with subsequent nitric oxide consumption as causative. We sought to evaluate whether the infusion of PBSC grafts containing lysed red blood cells (RBCs) leads to the toxicity observed in transplant subjects.

Nitric oxide for inhalation in the acute treatment of sickle cell pain crisis: a randomized controlled trial.

Context: Inhaled nitric oxide has shown evidence of efficacy in mouse models of sickle cell disease (SCD), case series of patients with acute chest syndrome, and 2 small placebo-controlled trials for treatment of vaso-occlusive pain crisis (VOC).

Objective: To determine whether inhaled nitric oxide gas reduces the duration of painful crisis in patients with SCD who present to the emergency department or hospital for care.

Design, Setting, And Participants: Prospective, multicenter, double-blind, randomized, placebo-controlled clinical trial for up to 72 hours of inhaled nitric oxide gas vs inhaled nitrogen placebo in 150 participants presenting with VOC of SCD at 11 centers between October 5, 2004, and December 22, 2008.

Endothelin receptor antagonists for pulmonary hypertension in adult patients with sickle cell disease.

Pulmonary Hypertension is a serious complication of sickle cell disease (SCD), with high morbidity and mortality. Endothelin (ET)-1, a potent vasoconstrictor elevated in SCD, acts through the ET receptors (ETR), ETR-A and ETR-B. Bosentan and ambrisentan are ETR blockers used in primary pulmonary hypertension.

Hemodynamic and functional assessment of patients with sickle cell disease and pulmonary hypertension.

Rationale: Although pulmonary hypertension (PH) is a common complication of sickle cell disease (SCD) associated with high mortality, there exist few data characterizing hemodynamics and cardiopulmonary function in this population.

Objectives: To characterize hemodynamics and cardiopulmonary function in patients with SCD with and without PH.

Methods: Patients with SCD with PH (n = 26) were compared with control subjects with SCD but without PH (n = 17), matched for age, hemoglobin levels, and fetal hemoglobin levels.

Diastolic dysfunction is an independent risk factor for death in patients with sickle cell disease.

Objectives: The goal of this study was to characterize left ventricular diastolic function in the sickle cell disease (SCD) population and to relate echocardiographic measures of dysfunction with pulmonary hypertension and mortality.

Background: Pulmonary hypertension has been identified as a predictor of death in the adult SCD population. Although diastolic dysfunction is also observed in this population, its prevalence, association with high pulmonary artery systolic pressure, and attributable mortality remain unknown.

Severity of pulmonary hypertension during vaso-occlusive pain crisis and exercise in patients with sickle cell disease.

Pulmonary hypertension is associated with sudden death and is a risk factor for mortality in adult patients with sickle cell disease. The high mortality despite only mild-to-moderate increases in pulmonary vascular resistance remains an unresolved paradox. Accordingly, little is known about the cardiovascular effects of stressors, such as vaso-occlusive pain crisis (VOC) and exercise, which may acutely increase pulmonary pressures and impair right heart function.

Levels of soluble endothelium-derived adhesion molecules in patients with sickle cell disease are associated with pulmonary hypertension, organ dysfunction, and mortality.

Endothelial cell adhesion molecules orchestrate the recruitment and binding of inflammatory cells to vascular endothelium. With endothelial dysfunction and vascular injury, the levels of endothelial bound and soluble adhesion molecules increase. Such expression is modulated by nitric oxide (NO), and in patients with sickle cell disease (SCD), these levels are inversely associated with measures of NO bioavailability.

Sildenafil therapy in patients with sickle cell disease and pulmonary hypertension.

Unlabelled: Pulmonary hypertension is a frequent complication of sickle cell disease that is associated with haemolysis, impaired nitric oxide bioavailability and high mortality. We sought to evaluate the safety and efficacy of selective pulmonary vasodilators and antiproliferative agents in this at-risk population. After optimising sickle cell disease therapy to stabilise haemoglobin and fetal haemoglobin levels, we evaluated the safety and efficacy of sildenafil in 12 patients with sickle cell disease and pulmonary hypertension.

Pulmonary hypertension as a risk factor for death in patients with sickle cell disease.

Background: The prevalence of pulmonary hypertension in adults with sickle cell disease, the mechanism of its development, and its prospective prognostic significance are unknown.

Methods: We performed Doppler echocardiographic assessments of pulmonary-artery systolic pressure in 195 consecutive patients (82 men and 113 women; mean [+/-SD] age, 36+/-12 years). Pulmonary hypertension was prospectively defined as a tricuspid regurgitant jet velocity of at least 2.

Divergent nitric oxide bioavailability in men and women with sickle cell disease.

Background: Although reduced endothelial nitric oxide (NO) bioavailability has been demonstrated in arteriosclerotic vascular disease, the integrity of this system in sickle cell disease remains uncertain.

Methods And Results: We measured forearm blood flow in 21 patients with sickle cell disease (hemoglobin SS genotype) and 18 black control subjects before and after intra-arterial infusions of acetylcholine, nitroprusside, and the NO synthase inhibitor NG-monomethyl-L-arginine (L-NMMA). Endothelium-dependent vasodilation, measured by the percent increase in flow induced by acetylcholine infusion, was significantly greater than in controls (252+/-37% for patients versus 134+/-24% for controls; P<0.

Telepathology.

The development of a Queensland-wide videoconferencing network provided an opportunity to develop telepathology. In 1999, weekly videoconferences began with remote laboratories and clinical staff in four peripheral hospitals and the Royal Brisbane Hospital and in 2000 biweekly videoconference pathology grand rounds started across Queensland with up to six sites, from Cairns to the Gold Coast, joining in or presenting. The average number of sites connected was 3.