ABSTRACT
We conducted a retrospective analysis of WT1-mutated acute myeloid leukemia (AML) patients who underwent allogeneic stem cell transplant. Thirty-seven patients with WT1-mutated AML were identified. Primary induction failure (40%) and early relapse rate (18%) after idarubicin/cytarabine (7 + 3) chemotherapy were observed. All patients with induction failure subsequently achieved CR with additional chemotherapy. There was no significant difference between outcomes after myeloablative vs. reduced intensity (Fludarabine/Melphalan [Flu/Mel]) conditioning regimens. RFS but not OS was significantly better in patients who received FLAG-IDA prior to transplant and/or a fludarabine-containing conditioning. In an independent ex vivo study, WT1-mutated AML samples exhibited greater sensitivity to fludarabine (p = 0.026) and melphalan (p = 0.0005) than non-WT1-mutated AML samples while there was no difference between sensitivity to cytarabine. Our data favor using a fludarabine-based induction for AML with WT1 mutation instead of 7 + 3. Fludarabine conditioning regimens for alloHCT showed better RFS but not OS.
Subject(s)
Leukemia, Myeloid, Acute , Melphalan , Humans , Melphalan/therapeutic use , Retrospective Studies , Antineoplastic Combined Chemotherapy Protocols/adverse effects , Leukemia, Myeloid, Acute/diagnosis , Leukemia, Myeloid, Acute/drug therapy , Leukemia, Myeloid, Acute/genetics , Idarubicin/therapeutic use , Cytarabine/therapeutic use , WT1 Proteins/geneticsABSTRACT
Acquired hypoganglionosis (HG) is a rare enteric gastrointestinal neuromuscular disorder previously associated with chronic inflammation that can lead to constipation, ileus, and even death. There is little known about the pathophysiology of acquired hypoganglionosis, and it is unclear if medications are related to the development of the disease. Clozapine is an atypical antipsychotic used to treat refractory schizophrenia that is well known for its side effects including agranulocytosis and gastrointestinal dysmotility. This is an unusual case of acquired hypoganglionosis in a patient with anticholinergic toxicity on clozapine therapy.
ABSTRACT
ABSTRACT: Venous thromboembolism (VTE) is an important complication of major orthopedic surgery (total hip arthroplasty-THA, total knee arthroplasty-TKA, hip fracture surgery-FHS) and is associated with significant morbidity and mortality. Despite this, not all patients receive an appropriate prophylaxis, often due to a disproportionate fear of bleeding complications. A challenge in the management of VTE prophylaxis is to balance the benefits of the treatment with the risk of bleeding. In this article, we review the latest guidelines recommendations regarding prevention of postoperative VTE in patients undergoing orthopedic surgery.
ABSTRACT
Ischemic preconditioning (IPC) of the brain describes the neuroprotection induced by a short, conditioning ischemic episode (CIE) to a subsequent severe (test) ischemic episode (TIE). Most of the supporting evidence for IPC is based on histological assessment, several days after TIE. The aim of this study is to investigate if changes induced by IPC can be detected within 30 min of reperfusion following the ischemic episode. A rat model of "four-vessel occlusion" transient global cerebral ischemia and parametric analysis of electrocorticogram were used. A control group was subjected directly to a 10 min TIE, and in a preconditioned group TIE was induced 48 h after a 3 min CIE. Quantitative histology was performed 48 h after TIE. Our key finding is that, 30 min after reperfusion, there is a significant increase in the electrocortical slow activity in the control group but not in the preconditioned group. Moreover the increase inversely correlates with the degree of electrocortical suppression during seconds 10 to 15 after the onset of the ischemic episode.