Recombinant humanized anti-IL-2 receptor antibody (daclizumab) produces responses in patients with moderate aplastic anemia

In contrast to severe aplastic anemia (sAA), the appropriate management of patients with moderate pancytopenia is unclear. In this study, we examined the efficacy of a humanized monoclonal antibody recognizing interleukin-2 receptor (daclizumab), which has proven to be a successful immunosuppressive agent in solid organ and bone marrow transplantation. We treated 17 patients with moderate aplastic anemia (mAA) with 1 mg/kg every 2 weeks for 3 months. mAA was defined as depression of 2 of the 3 blood counts: absolute neutrophil count 1200/mm3 or less, platelet count 70,000/mm3 or less, hemoglobin level 8.5 g/dL or lower, and absolute reticulocyte count 60,000/mm3 or less. The primary end point of our protocol was a hematologic response in at least one affected peripheral blood value. Daclizumab had little toxicity. Six of the 16 (38%) evaluable patients responded to treatment. Two patients with previously chronic disease showed complete return of normal counts, which were sustained for more than 2 years following treatment. Four patients had single-lineage responses. Two previously transfusion-dependent patients became transfusion independent; one patient with many neutropenia-related infections had a normal neutrophil count following treatment. Daclizumab appears safe; its efficacy in this pilot protocol suggests that expanded study of this monoclonal antibody in immune-mediated bone marrow failure syndrome is warranted.     

Predicting successful prosthetic rehabilitation in major lower-limb amputation patients: a 15-year retrospective cohort study

Objective

To determine and compare specific factors that could be associated and predictive with successful prosthetic rehabilitation in major lower-limb amputations.

Tests of calibration and goodness‐of‐fit in the survival setting

To access the calibration of a predictive model in a survival analysis setting, several authors have extended the Hosmer–Lemeshow goodness‐of‐fit test to survival data. Grønnesby and Borgan developed a test under the proportional hazards assumption, and Nam and D'Agostino developed a nonparametric test that is applicable in a more general survival setting for data with limited censoring. We analyze the performance of the two tests and show that the Grønnesby–Borgan test attains appropriate size in a variety of settings, whereas the Nam‐D'Agostino method has a higher than nominal Type 1 error when there is more than trivial censoring. Both tests are sensitive to small cell sizes. We develop a modification of the Nam‐D'Agostino test to allow for higher censoring rates. We show that this modified Nam‐D'Agostino test has appropriate control of Type 1 error and comparable power to the Grønnesby–Borgan test and is applicable to settings other than proportional hazards. We also discuss the application to small cell sizes. Copyright © 2015 John Wiley & Sons, Ltd.     

A 19 year follow‐up of a woman with lipoprotein lipase deficiency treated with biliopancreatic diversion

We show the long‐term efficacy and safety of modified biliopancreatic diversion for the treatment of LPL‐deficiency. How this option compares with gene therapy is difficult to evaluate due to limited experience. Surgery may be the first option in patients in whom medical therapy is ineffective and gene therapy not applicable.     

Two Cases of Prenatally Diagnosed Membranous and Muscular Ventricular Septal Aneurysms

A ventricular septal aneurysm is a rare heart defect located in the muscular or membranous part of the septum. Muscular ventricular septal aneurysms are usually isolated, with a favorable prognosis. Membranous ventricular septal aneurysms are often associated with other heart anomalies, could result in serious complications, and may require surgical treatment. We describe 2 cases of prenatally diagnosed ventricular septal aneurysms: an isolated membranous ventricular septal aneurysm with a good outcome, which was initially misdiagnosed as an atrioventricular septal defect; and a muscular ventricular septal aneurysm associated with a hypoplastic aortic arch and severe hydrocephaly, which resulted in termination of the pregnancy. To our knowledge, the combination of a muscular ventricular septal aneurysm with an extracardiac anomaly has not been reported previously.