Recombinant ADAMTS13 for Immune Thrombotic Thrombocytopenic Purpura.

In patients with immune thrombotic thrombocytopenic purpura (iTTP), autoantibodies against the metalloprotease ADAMTS13 lead to catastrophic microvascular thrombosis. However, the potential benefits of recombinant human ADAMTS13 (rADAMTS13) in patients with iTTP remain unknown. Here, we report the clinical use of rADAMTS13, which resulted in the rapid suppression of disease activity and complete recovery in a critically ill patient whose condition had proved to be refractory to all available treatments. We also show that rADAMTS13 causes immune complex formation, which saturates the autoantibody and may promote its clearance. Our data support the role of rADAMTS13 as a novel adjunctive therapy in patients with iTTP.

A case of syngeneic graft-versus-host disease.

Graft-versus-host disease has been reported to occur rarely in syngeneic hematopoietic stem cell transplant recipients. Clinical and histological changes consistent with graft-versus-host disease have been reported to occur in this patient population. We report a case of a 46-year-old Caucasian male with diffuse large B-cell lymphoma in complete remission who underwent a syngeneic hematopoietic stem cell transplant. He was diagnosed with grade III acute skin and gastrointestinal graft-versus-host disease requiring high-dose corticosteroids and immunosuppressive therapy and resulting in a complete response. Syngeneic graft-versus-host disease is an anomaly that needs to be considered as a differential diagnosis of patients experiencing dermatitis, gastroenteritis, or hepatitis after an identical twin hematopoietic stem cell transplant.

Treatment with Dalteparin is Associated with a Lower Risk of Bleeding Compared to Treatment with Unfractionated Heparin in Patients with Renal Insufficiency.

BACKGROUND: Low molecular weight heparins (LMWHs) have been cautiously used in patients with chronic kidney disease (CKD) due to fear of accumulation. Dalteparin, however, has shown minimal tendency to accumulate in patients with CKD and may be safe to use in this patient population. OBJECTIVE: We compared the incidence of clinically significant bleeding in patients with CKD receiving therapeutic doses of dalteparin to that of patients with CKD receiving therapeutic doses of UFH. DESIGN: This was a retrospective cohort study. SUBJECTS: Inpatients with CKD (GFR < 60 ml/min) who were treated with therapeutic dalteparin or UFH were included in the study MAIN MEASURES: Primary outcome was major bleeding within 10 days of anticoagulation, identified by ICD-9 code and confirmed by chart review. Demographic characteristics, laboratory values, comorbidities, prior bleeding history and inpatient medications were extracted for each admission from the electronic medical record. Logistic regression models were created to examine the association between choice of anticoagulant and bleeding rates, after adjustment for demographic and clinical characteristics. KEY RESULTS: Dalteparin-treated patients were significantly less likely to experience a major bleed than patients treated with UFH (1.14 % vs. 3.49 %, p < 0.001). The reduced likelihood of bleeding associated with dalteparin treatment remained significant after adjustment for patient characteristics (HR 0.39, 95 % CI: 0.21-0.70, p < 0.0001). A stratified analysis for subgroups with GFR< 30 mL/min and with GFR between 30 and 60 mL/min showed that dalteparin was still associated with lower odds of bleeding compared to treatment with unfractionated heparin, but the difference was nonsignificant for GFR< 30 (HR 0.35, 95 % CI: 0.11-1.15), even after adjustment (OR 0.37, 95 % CI: 0.11-1.22). CONCLUSION: In patients with CKD, treatment with therapeutic dose dalteparin was associated with lower rates of bleeding than treatment with unfractionated heparin. For patients with severe CKD (GFR< 30), dalteparin was shown to be at least as safe as unfractionated heparin.

A high-fiber diet does not protect against asymptomatic diverticulosis.

BACKGROUND & AIMS: The complications of diverticulosis cause considerable morbidity in the United States; health care expenditures for this disorder are estimated to be $2.5 billion per year. Many physicians and patients believe that a high-fiber diet and frequent bowel movements prevent the development of diverticulosis. Evidence for these associations is poor. We sought to determine whether low-fiber or high-fat diets, diets that include large quantities of red meat, constipation, or physical inactivity increase risk for asymptomatic diverticulosis. METHODS: We performed a cross-sectional study of 2104 participants, 30-80 years old, who underwent outpatient colonoscopy from 1998 to 2010. Diet and physical activity were assessed in interviews using validated instruments. RESULTS: The prevalence of diverticulosis increased with age, as expected. High intake of fiber did not reduce the prevalence of diverticulosis. Instead, the quartile with the highest fiber intake had a greater prevalence of diverticulosis than the lowest (prevalence ratio = 1.30; 95% confidence interval, 1.13-1.50). Risk increased when calculated based on intake of total fiber, fiber from grains, soluble fiber, and insoluble fiber. Constipation was not a risk factor. Compared to individuals with <7 bowel movements per week, individuals with >15 bowel movements per week had a 70% greater risk for diverticulosis (prevalence ratio = 1.70; 95% confidence interval, 1.24-2.34). Neither physical inactivity nor intake of fat or red meat was associated with diverticulosis. CONCLUSIONS: A high-fiber diet and increased frequency of bowel movements are associated with greater, rather than lower, prevalence of diverticulosis. Hypotheses regarding risk factors for asymptomatic diverticulosis should be reconsidered.

Human Herpes Virus-6 Encephalitis Following Autologous Blood and Marrow Transplant.

Human herpesvirus-6 (HHV-6) is a highly prevalent virus that establishes lifelong latency in human hosts. Symptomatic HHV-6 reactivation rarely occurs in immunocompetent individuals and is best described in immunosuppressed patients such as recipients of bone marrow transplants (BMT). In that setting, HHV-6 reactivation has been associated with fever, rash, pneumonitis, encephalitis, and delayed engraftment. While these complications are well documented in allogeneic transplant, the clinical impact of such reactivation is not well known in autologous BMT. We described a case of HHV-6-associated encephalitis in a previously heavily treated patient with multiple myeloma (MM) following a second autologous BMT, and discuss the need for clinicians to be aware of the potential clinical impact of HHV-6 following autologous BMT in the era of immunomodulatory agents.