Phase I dose escalation study of IO-108, an anti-LILRB2 antibody, in patients with advanced solid tumors.

Purpose: In this first-in-human dose escalation study, the safety and efficacy of IO-108, a fully human monoclonal antibody targeting leukocyte immunoglobulin-like receptor B2 (LILRB2), was investigated in patients with advanced solid tumors as monotherapy and in combination with pembrolizumab, an anti-programmed cell death protein 1 (PD-1) antibody.

Methods: The study included patients with histologically or cytologically confirmed advanced and relapsed solid tumors, with measurable disease by Response Evaluation Criteria In Solid Tumors (RECIST) V.1.

Factors influencing mercury exposure in Arctic-breeding shorebirds.

Mercury (Hg) pollution remains a concern to Arctic ecosystems, due to long-range transport from southern industrial regions and melting permafrost and glaciers. The objective of this study was to identify intrinsic, extrinsic, and temporal factors influencing Hg concentrations in Arctic-breeding shorebirds and highlight regions and species at greatest risk of Hg exposure. We analyzed 1094 blood and 1384 feather samples from 12 shorebird species breeding at nine sites across the North American Arctic during 2012 and 2013.

ArcticBirdSounds: An open-access, multiyear, and detailed annotated dataset of bird songs and calls.

Tracking biodiversity shifts is central to understanding past, present, and future global changes. Recent advances in bioacoustics and the low cost of high-quality automatic recorders are revolutionizing studies in biogeography and community and behavioral ecology with a robust assessment of phenology, species occurrence, and individual activity. This large volume of acoustic recordings has recently generated a plethora of datasets that can now be handled automatically, mostly via big data methods such as deep learning.

Sympatrically breeding congeneric seabirds ( spp.) from Arctic Canada migrate to four oceans.

Polar systems of avian migration remain unpredictable. For seabirds nesting in the Nearctic, it is often difficult to predict which of the world's oceans birds will migrate to after breeding. Here, we report on three related seabird species that migrated across four oceans following sympatric breeding at a central Canadian high Arctic nesting location.

The annual cycle for whimbrel populations using the Western Atlantic Flyway.

Many long-distance migratory birds use habitats that are scattered across continents and confront hazards throughout the annual cycle that may be population-limiting. Identifying where and when populations spend their time is fundamental to effective management. We tracked 34 adult whimbrels (Numenius phaeopus) from two breeding populations (Mackenzie Delta and Hudson Bay) with satellite transmitters to document the structure of their annual cycles.

Whimbrel populations differ in trans-atlantic pathways and cyclone encounters.

Each year hundreds of millions of birds cross the Atlantic Ocean during the peak of tropical cyclone activity. The extent and consequences of migrant-storm interactions remain unknown. We tracked whimbrels from two populations (Mackenzie Delta; Hudson Bay) to examine overlap between migration routes and storm activity and both the frequency and consequence of storm encounters.

Flower-visitor communities of an arcto-alpine plant-Global patterns in species richness, phylogenetic diversity and ecological functioning.

Pollination is an ecosystem function of global importance. Yet, who visits the flower of specific plants, how the composition of these visitors varies in space and time and how such variation translates into pollination services are hard to establish. The use of DNA barcodes allows us to address ecological patterns involving thousands of taxa that are difficult to identify.

Unexpected diversity in socially synchronized rhythms of shorebirds.

The behavioural rhythms of organisms are thought to be under strong selection, influenced by the rhythmicity of the environment. Such behavioural rhythms are well studied in isolated individuals under laboratory conditions, but free-living individuals have to temporally synchronize their activities with those of others, including potential mates, competitors, prey and predators. Individuals can temporally segregate their daily activities (for example, prey avoiding predators, subordinates avoiding dominants) or synchronize their activities (for example, group foraging, communal defence, pairs reproducing or caring for offspring).

Romiplostim Treatment in Adults with Immune Thrombocytopenia of Varying Duration and Severity.

Romiplostim is recommended for the second- and third-line treatment of primary immune thrombocytopenia (ITP). We conducted a large, single-arm study (clinicaltrials.gov; NCT00508820) with broad entry criteria to evaluate the safety of romiplostim in adult ITP.

Results of a randomized, double-blind study of romiplostim versus placebo in patients with low/intermediate-1-risk myelodysplastic syndrome and thrombocytopenia.

Background: Thrombocytopenia in patients with myelodysplastic syndrome (MDS) is associated with shortened survival and an increased risk of evolution to acute myeloid leukemia (AML). In this study, the authors evaluated the efficacy of romiplostim in patients who had thrombocytopenia with low-risk/intermediate-1-risk MDS.

Methods: Patients who had thrombocytopenia with low-risk/intermediate-1-risk MDS (N = 250) were randomized 2:1 to receive romiplostim or placebo weekly for 58 weeks.

Long-term safety and tolerability of romiplostim in patients with primary immune thrombocytopenia: a pooled analysis of 13 clinical trials.

Background And Objectives: Thrombopoietin receptor agonists (TPOra) are the only treatments for immune thrombocytopenia (ITP) for which evidence of efficacy and safety from randomized, placebo-controlled trials is available. We sought to determine the long-term tolerability of the TPOra romiplostim, with a particular focus on thrombosis, bleeding, bone marrow (BM) reticulin, neoplasms/haematological malignancies and fatal events.

Methods: Data from 13 romiplostim clinical trials in which 653 patients with ITP received romiplostim for up to 5 yr (921.

Unrelated donor bone marrow transplantation for myelodysplastic syndrome in children.

We describe long-term disease-free survival (DFS) after unrelated donor bone marrow transplantation (BMT) for myelodysplastic syndrome (MDS) in 118 patients aged ≤18 years. Forty-six patients had refractory cytopenia (RC), 55 refractory anemia with excess blasts (RAEB), and 17 refractory anemia with excess blasts in transformation (RAEB-t). Transplant-related mortality was higher after mismatched BMT (relative risk [RR] 3.

Clinical utility of computed tomography screening of chest, abdomen, and sinuses before hematopoietic stem cell transplantation: the St. Jude experience.

All allogeneic (allo) and autologous (auto) hematopoietic stem cell transplantation (HSCT) recipients at St. Jude Children's Research Hospital undergo pre-HSCT computed tomography (CT) of the sinuses, chest, and abdomen because they are at significant risk for opportunistic infections. We studied whether this extensive routine imaging is warranted to detect infection despite the risk of additional radiation exposure.

Total and active rabbit antithymocyte globulin (rATG;Thymoglobulin) pharmacokinetics in pediatric patients undergoing unrelated donor bone marrow transplantation.

Rabbit antithymocyte globulin (rATG; Thymoglobulin) is currently used to prevent or treat graft-versus-host disease (GVHD) during hematopoietic stem cell transplantation (HSCT). The dose and schedule of rATG as part of the preparative regimen for unrelated donor (URD) bone marrow transplantation (BMT) have not been optimized in pediatric patients. We conducted a prospective study of 13 pediatric patients with hematologic malignancies undergoing URD BMT at St.

Changes in outcomes (1996-2004) for pediatric oncology and hematopoietic stem cell transplant patients requiring invasive mechanical ventilation.

Objective: To assess the following hypotheses regarding mechanically ventilated pediatric oncology patients, including those receiving hematopoietic stem cell transplant (HSCT) and those not receiving HSCT: 1) outcomes are more favorable for nontransplant oncology patients than for those requiring HSCT; 2) outcomes have improved for both populations over time; and 3) there are factors available during the time of mechanical ventilation that identify patients with a higher likelihood of dying.

Design: Retrospective review.

Setting: Free-standing, tertiary care, pediatric hematology oncology hospital.

Diagnostic yield of bronchoalveolar lavage is low in allogeneic hematopoietic stem cell recipients receiving immunosuppressive therapy or with acute graft-versus-host disease: the St. Jude experience, 1990-2002.

Management of pulmonary complications after hematopoietic stem cell transplantation (HSCT) often includes bronchoalveolar lavage (BAL), but the diagnostic yield of BAL remains unclear in pediatric HSCT patients. We reviewed the records of 78 allogeneic and 11 autologous transplant recipients who underwent BAL after HSCT at St. Jude Children's Research Hospital (1990-2002).

Rapid immune reconstitution after a reduced-intensity conditioning regimen and a CD3-depleted haploidentical stem cell graft for paediatric refractory haematological malignancies.

The main obstacles to successful haploidentical haematopoietic stem cell transplantation from a mismatched family member donor are delayed immune reconstitution, vulnerability to infections and severe graft-versus-host disease (GvHD). We designed a reduced-intensity conditioning regimen that excluded total body irradiation and anti-thymocyte globulin in order to expedite immune reconstitution after a CD3-depleted haploidentical stem cell transplant. This protocol was used to treat 22 paediatric patients with refractory haematological malignancies.

Diagnostic challenge in recurrent skin rash after autologous bone marrow transplantation.

Engraftment syndrome, autologous graft-versus-host disease (GVHD), and infection after autologous hematopoietic cell transplantation can have similar clinical presentations. Here, we describe a patient with refractory Ewing sarcoma who had recurrent skin rash after autologous hematopoietic cell transplantation. Although the rash was diagnosed as GVHD histologically, this case illustrates the diagnostic dilemma of distinguishing engraftment syndrome, autologous GVHD, or concomitant viral infection.

Cidofovir for the treatment of adenoviral infection in pediatric hematopoietic stem cell transplant patients.

Background: Adenovirus (ADV) infections are associated with significant morbidity and mortality after hematopoietic stem cell transplantation (HSCT). The virus is endemic in the general pediatric population and frequently causes severe disease in immunocompromised patients, especially children. We report our experience with cidofovir (CDV) for treatment of ADV infection in 57 HSCT patients, median age 8 years (range 0.

EBV lymphoproliferative disease of host origin after haploidentical stem cell transplantation.

Post-transplant lymphoproliferative disease (PTLPD), due to the reactivation of Epstein-Barr virus (EBV), is a serious complication. The risk of the disorder increases with T-cell depletion methods, mismatched hematopoietic stem cell transplantation (HSCT), graft-versus-host disease (GVHD), and immunosuppression. In contrast to solid organ transplantation, where EBV is typically of recipient origin, the source of the EBV in HSCT recipients is donor-derived B-lymphocytes.

Outcome of hematopoietic stem cell transplantation for pediatric patients with therapy-related acute myeloid leukemia or myelodysplastic syndrome.

Background: Therapy-related myelodysplastic syndrome (t-MDS) and acute myeloid leukemia (t-AML) carry a poor prognosis. We analyzed the results of allogeneic HSCT in 38 children to determine which factors, if any, affected outcome.

Procedure: The effects of demographic, donor, and disease-related factors were analyzed to determine their effects on overall and disease-free survival (OS, DFS), relapse, and non-relapse mortality (NRM).

Brain parenchymal damage after haematopoietic stem cell transplantation for severe sickle cell disease.

Prospective magnetic resonance imaging (MRI), magnetic resonance angiography (MRA), neuropsychological testing and neurological examinations were performed to determine the long-term effect of successful haematopoietic stem cell transplantation on the neurological status of nine children with sickle cell disease. A scoring system for severity of brain parenchymal and vascular lesions was developed and applied. Neurological examinations and neuropsychometric tests were stable, but MRI and MRA studies were not.

Safety and efficacy of enzyme replacement therapy in combination with hematopoietic stem cell transplantation in Hurler syndrome.

Purpose: Hurler syndrome is a debilitating genetic disease with a typical life span of 5 to 8 years. Early hematopoietic stem cell transplantation (HSCT) mitigates disease symptoms and improves survival. However, morbidity and mortality associated with HSCT can limit its success.

Pulmonary nodular lesions in bone marrow transplant recipients: impact of histologic diagnosis on patient management and prognosis.

Bone marrow transplantation is associated with numerous pulmonary complications, which may manifest as nodules. We studied 33 bone marrow transplant (BMT) recipients in whom pulmonary nodular lesions (PNLs) developed during a 5-year period and who underwent open lung biopsy (OLB) for diagnosis. Of 33 patients with PNL, 15 (45%) had pulmonary cytolytic thrombi (PCT), a recently described condition characterized histologically by occlusive vascular lesions and hemorrhagic infarcts and clinically by a favorable outcome.

Etiology and outcome of graft failure in pediatric hematopoietic stem cell transplant recipients.

Purpose: To determine the incidence, etiology and outcome of graft failure in pediatric allogeneic bone marrow transplant (BMT) recipients.

Patients And Methods: Patients with primary or secondary graft failure were identified by database review. A retrospective chart review was performed.