Adjudication of Hospitalizations and Deaths in the IRONMAN Trial of Intravenous Iron for Heart Failure.

Background: Patients with heart failure and iron deficiency have diverse causes for hospitalization and death that might be affected by iron repletion.

Objectives: The purpose of this study was to explore causes of hospitalizations and deaths in a randomized trial (IRONMAN) of heart failure comparing intravenous ferric derisomaltose (FDI) (n = 568) and usual care (n = 569).

Methods: Patients with heart failure, left ventricular ejection fraction ≤45%, and either transferrin saturation <20% or serum ferritin <100 μg/L were enrolled.

Molecular-guided therapy for the treatment of patients with relapsed and refractory childhood cancers: a Beat Childhood Cancer Research Consortium trial.

Background: Children with relapsed central nervous system (CNS tumors), neuroblastoma, sarcomas, and other rare solid tumors face poor outcomes. This prospective clinical trial examined the feasibility of combining genomic and transcriptomic profiling of tumor samples with a molecular tumor board (MTB) approach to make real‑time treatment decisions for children with relapsed/refractory solid tumors.

Methods: Subjects were divided into three strata: stratum 1-relapsed/refractory neuroblastoma; stratum 2-relapsed/refractory CNS tumors; and stratum 3-relapsed/refractory rare solid tumors.

Combined Immunotherapy Improves Outcome for Replication-Repair-Deficient (RRD) High-Grade Glioma Failing Anti-PD-1 Monotherapy: A Report from the International RRD Consortium.

Unlabelled: Immune checkpoint inhibition (ICI) is effective for replication-repair-deficient, high-grade gliomas (RRD-HGG). The clinical/biological impact of immune-directed approaches after failing ICI monotherapy is unknown. We performed an international study on 75 patients treated with anti-PD-1; 20 are progression free (median follow-up, 3.

Provocative questions in osteosarcoma basic and translational biology: A report from the Children's Oncology Group.

Patients who are diagnosed with osteosarcoma (OS) today receive the same therapy that patients have received over the last 4 decades. Extensive efforts to identify more effective or less toxic regimens have proved disappointing. As we enter a postgenomic era in which we now recognize OS not as a cancer of mutations but as one defined by p53 loss, chromosomal complexity, copy number alteration, and profound heterogeneity, emerging threads of discovery leave many hopeful that an improving understanding of biology will drive discoveries that improve clinical care.

Osteosarcoma enters a post genomic era with in silico opportunities: Generation of the High Dimensional Database for facilitating sarcoma biology research: A report from the Children's Oncology Group and the QuadW Foundation.

The prospective banking of osteosarcoma tissue samples to promote research endeavors has been realized through the establishment of a nationally centralized biospecimen repository, the Children's Oncology Group (COG) biospecimen bank located at the Biopathology Center (BPC)/Nationwide Children's Hospital in Columbus, Ohio. Although the physical inventory of osteosarcoma biospecimens is substantive (>15,000 sample specimens), the nature of these resources remains exhaustible. Despite judicious allocation of these high-value biospecimens for conducting sarcoma-related research, a deeper understanding of osteosarcoma biology, in particular metastases, remains unrealized.

Severe combined immunodeficiency (SCID) presenting with neonatal aplastic anemia.

Aplastic anemia in the neonate is rare. We report a case of severe combined immunodeficiency (SCID) presenting with neonatal aplastic anemia. This report highlights the importance of considering SCID early in the evaluation of neonatal aplastic anemia prior to the development of infectious complications.

A summary of the osteosarcoma banking efforts: a report from the Children's Oncology Group and the QuadW Foundation.

Background: Survival rates of patients with osteosarcoma have remained stagnant over the last thirty years. Better understanding of biology, new therapeutics, and improved biomarkers are needed. The Children's Oncology Group (COG) addressed this need by developing one of the largest osteosarcoma biorepositories ever, containing over 15,000 tumor and tissue samples from over 1,500 patients.

TYK2-STAT1-BCL2 pathway dependence in T-cell acute lymphoblastic leukemia.

Unlabelled: Targeted molecular therapy has yielded remarkable outcomes in certain cancers, but specific therapeutic targets remain elusive for many others. As a result of two independent RNA interference (RNAi) screens, we identified pathway dependence on a member of the Janus-activated kinase (JAK) tyrosine kinase family, TYK2, and its downstream effector STAT1, in T-cell acute lymphoblastic leukemia (T-ALL). Gene knockdown experiments consistently showed TYK2 dependence in both T-ALL primary specimens and cell lines, and a small-molecule inhibitor of JAK activity induced T-ALL cell death.

Kinase pathway dependence in primary human leukemias determined by rapid inhibitor screening.

Kinases are dysregulated in most cancers, but the frequency of specific kinase mutations is low, indicating a complex etiology in kinase dysregulation. Here, we report a strategy to rapidly identify functionally important kinase targets, irrespective of the etiology of kinase pathway dysregulation, ultimately enabling a correlation of patient genetic profiles to clinically effective kinase inhibitors. Our methodology assessed the sensitivity of primary leukemia patient samples to a panel of 66 small-molecule kinase inhibitors over 3 days.

An adaptive Src-PDGFRA-Raf axis in rhabdomyosarcoma.

Alveolar rhabdomyosarcoma (aRMS) is a very aggressive sarcoma of children and young adults. Our previous studies have shown that small molecule inhibition of Pdgfra is initially very effective in an aRMS mouse model. However, slowly evolving, acquired resistance to a narrow-spectrum kinase inhibitor (imatinib) was common.

In vitro sensitivity to dasatinib in lymphoblasts from a patient with t(17;19)(q22;p13) gene rearrangement pre-B acute lymphoblastic leukemia.

Patients with t(17;19) acute lymphoblastic leukemia (ALL) have a dismal prognosis even with the most intensive current therapies that include stem cell transplant. We present the case of a patient with t(17;19)(q22;p13) gene rearranged B-cell precursor ALL whose lymphoblasts were found to have significant in vitro sensitivity to dasatinib. The patient tolerated the addition of dasatinib with combination therapy and remained in remission for over nine months until his recurrence.

Scarfette osteotomy for surgical treatment of bunionette deformity.

Numerous procedures have been described for a bunionette deformity. Choosing a specific osteotomy depends largely on the degree of the deformity and surgeon preference. The Scarfette osteotomy is a versatile procedure that addresses specific etiologic factors associated with bunionette deformities.

Percutaneous fixation of forefoot, midfoot, hindfoot, and ankle fracture dislocations.

Open reduction with rigid internal fixation is the basic principle for surgical management in foot and ankle trauma. High-risk patients present a surgical dilemma for the foot and ankle surgeon because the possible complications are magnified in this patient population. Percutaneous fixation is a unique alternative for achieving anatomic stabilization without increased physical strain to the patient.

Early results of the Mau osteotomy for correction of moderate to severe hallux valgus: a review of 24 cases.

Unlabelled: In our retrospective study, we report the objective results of the Mau osteotomy in the treatment of hallux valgus. We reviewed the results of 24 cases of moderate to severe hallux valgus deformities corrected with the Mau osteotomy of the first metatarsal combined with a distal soft-tissue procedure. Follow-up was possible in 24 cases.

A comparison of the crescentic and Mau osteotomies for correction of hallux valgus.

Unlabelled: We retrospectively compared crescentic and Mau osteotomies used to treat a total of 39 cases of hallux abductovalgus. Follow-up was possible in 10 of the crescentic cases (mean 228 days) and 24 of the Mau cases (mean 245 days). Preoperatively, the mean first intermetatarsal and hallux abductus angles were 17.

A retrospective review of immediate weightbearing after first metatarsophalangeal joint arthrodesis.

First metatarsophalangeal (MTP) joint arthrodesis is a proven technique as a salvage procedure for many foot pathologies. Many studies have looked at joint preparation techniques, position of the fusion, and construct stability. In this retrospective study, the authors report the overall fusion rate after first MTP joint fusion with full immediate postoperative weightbearing.

A new minimally invasive technique for treating plantar fasciosis using bipolar radiofrequency: a prospective analysis.

The purpose of this study was to evaluate the effectiveness of a new minimally invasive technique using bipolar radiofrequency in the treatment of plantar fasciosis. A prospective study was performed on 10 patients with recalcitrant plantar fasciosis that failed conservative care. A percutaneous microtenotomy was performed unilaterally with a Topaz microdebrider.

Cost comparison of crossed screws versus dorsal plate construct for first metatarsophalangeal joint arthrodesis.

Unlabelled: Expensive surgical implants can significantly add to the cost of a procedure. We performed a crude cost analysis to evaluate and compare the crossed screw technique versus dorsal plating for first metatarsophalangeal arthrodesis. First metatarsophalangeal arthrodeses performed over a 20-month period were selected.