Dynamic Graft-versus-Host Disease-Free,Relapse-Free Survival: Multistate Modeling of the Morbidity and Mortality of Allotransplantation

Graft-versus-host disease (GVHD)-free, relapse-free survival (GRFS) represents complete, ideal recovery after allogeneic hematopoietic cell transplantation (HCT). However, as originally proposed, this composite endpoint does not account for the possibility that HCT complications may improve after treatment. To more accurately estimate survival with response to GVHD and relapse after HCT, we developed a dynamic multistate GRFS (dGRFS) model with outcomes data from 949 patients undergoing their first allogeneic HCT for hematologic malignancy at the University of Minnesota. Because some patients were successfully treated for GVHD and relapse, dGRFS was higher than the originally defined time-to-event GRFS at 1 year (37.0 versus 27.6%) through 4 years (37.4% versus 22.2%). Mean survival without failure events was .52 years (95% confidence interval, .45 to .58 year) greater in dGRFS compared with the originally defined GRFS. Patient age (P< .001), disease risk (P < .001), conditioning intensity (P = .007), and donor type (P = .003) all significantly influenced dGRFS. The multistate model of dGRFS closely estimates the continuing and prevalent severe morbidity and mortality of allogeneic HCT. To serve the greater HCT community in more accurately modeling recovery from transplantation, we provide our R code for determination of dGRFS with annotations in Supplementary Materials.     

Reduced-Intensity Conditioning Followed by Related and Unrelated Allografts for Hematologic Malignancies: Expanded Analysis and Long-Term Follow-Up

Reduced-intensity conditioning (RIC) extends the curative potential of allogeneic hematopoietic cell transplantation (HCT) to patients with hematologic malignancies unable to withstand myeloablative conditioning. We prospectively analyzed the outcomes of 292 consecutive patients, median age 58 years (range, 19 to 75) with hematologic malignancies treated with a uniform RIC regimen of cyclophosphamide, fludarabine, and total body irradiation (200 cGy) with or without antithymocyte globulin and cyclosporine and mycophenolate mofetil graft-versus-host disease (GVHD) prophylaxis followed by allogeneic HCT at the University of Minnesota from 2002 to 6. Probability of 5-year overall survival was 78% for patients with indolent non-Hodgkin lymphoma, 53% for chronic myelogenous leukemia, 55% for Hodgkin lymphoma, 40% for acute myelogenous leukemia, 37% for myelodysplastic syndrome, 29% for myeloma, and 14% for myeloproliferative neoplasms. Corresponding outcomes for relapse were 0%, 13%, 53%, 37%, 39%, 75%, and 29%, respectively. Disease risk index (DRI) predicted both survival and relapse with superior survival (64%) and lowest relapse (16%) in those with low risk score compared with 24% survival and 57% relapse in those with high/very-high risk scores. Recipient cytomegalovirus (CMV)-positive serostatus was protective from relapse with the lowest rates in those also receiving a CMV-positive donor graft (29%). The cumulative incidence of 2-year nonrelapse mortality was 26% and was lowest in those receiving a matched sibling graft at 21%, with low (21%) or intermediate (18%) HCT-specific comorbidity index, and was similar across age groups. The incidence of grades II to IV acute GVHD was 43% and grades III to IV 27%; the highest rates were found in those receiving an unrelated donor (URD) peripheral blood stem cell (PBSC) graft, at 50%. Chronic GVHD at 1 year was 36%.Future approaches incorporating alternative GVHD prophylaxis, particularly for URD PBSC grafts, and targeted post-transplant antineoplastic therapies for those with high DRI are indicated to improve these outcomes.     

The Role of Integrated Knowledge Translation in Intervention Research

There is widespread recognition across the full range of applied research disciplines, including health and social services, about the challenges of integrating scientifically derived research evidence into policy and/or practice decisions. These “disconnects” or “knowledge-practice gaps” between research production and use have spawned a new research field, most commonly known as either “implementation science” or “knowledge translation.” The present paper will review key concepts in this area, with a particular focus on “integrated knowledge translation” (IKT)—which focuses on researcher-knowledge user partnership—in the area of mental health and prevention of violence against women and children using case examples from completed and ongoing work. A key distinction is made between the practice of KT (disseminating, communicating, etc.), and the science of KT, i.e., research regarding effective KT approaches. We conclude with a discussion of the relevance of IKT for mental health intervention research with children and adolescents.     

Langerhans cell disease associated with pathological fracture of the mandible

A 27-year-old male suffered a fractured mandible following extraction of a tooth. It was subsequently found that the fracture occurred in an area pathologically weakened by a localized lesion of Langerhans cell disease. Since lesions of the jaws may be seen either as the first manifestation or as a complication of widespread Langerhans cell disease, the dentist has a major role in the diagnosis and management of such cases.     

A case of slipped capital femoral epiphysis results from hypophosphatemic rickets： treatment and midterm follow-up

In this case, a male patient presented with a clinically and radiographieally unstable slipped capital femoral epiphysis （SCFE） as well as slipped calcaneal epiphysis years. Subsequent thorough at the age of 23 work-up revealed that he had some features of rickets and labo- ratory test demonstrated he had hypophos- phatemia （2.3mg/dl）, normocalcemia, normal vi- tamin D metabolite levels, and secondary hy- perparathyroidism.     

Chagas' disease diagnosis: evaluation of several tests in blood bank screening

Blood transfusion is one of the principal routes of transmission of Chagas' disease, a major endemic disease in Latin America. Methods for blood screening are not accurate and may yield false results that lead to high social and economic costs. This study compares two methods of diagnosing Chagas' disease (indirect immunofluorescence and hemagglutination) and several enzyme-linked immunosorbent assays (ELISAs) with regard to specificity and sensitivity, by using human sera with known serologic and parasitologic characteristics, as well as samples with discrepant results on conventional serologic tests. An ELISA using recombinant antigens showed no cross-reactivity with sera that were positive for other diseases. All evaluated ELISAs performed well, and their use may lead to a reduction of more than 50 percent in the number of discordant sera. Further improvements are needed in view of the complexity of the serologic diagnosis of Chagas' disease.     

胎儿和新生儿同种异体免疫性血小板减少症:进展与持续性争议

胎儿和新生儿同种异体免疫性血小板减少症(AIT)是引起胎儿和新生儿严重血小板减少的最常见原因.母亲针对源自父亲的胎儿血小板抗原的IgG抗体,在妊娠早期就可通过胎盘,通常导致胎儿严重血小板减少.由于一些血小板减少症临界值(50、100或150×109/L)的不同,他们的发生率亦各不相同.但在多数未经选择的人群中,AIT影响1/1 000到1/2 000活产数.在新生儿病房,临床确诊的重症AIT很罕见,可能只有1:10 000分娩数.