Radioprotective Effects of ON 01210.Na upon Oral Administration

ON 01210.Na (Ex-RAD), a chlorobenzylsulfone derivative was investigated for its pharmacologic and radioprotective properties when administered via oral and subcutaneous (SC) routes. The goals of the study were to assess the comparative bioavailability of ON 01210.Na when administered by oral versus SC routes and to demonstrate that the oral drug delivery of ON 01210.Na afforded survival advantage similar to SC dosing. Pharmacokinetics was studied after two doses, 24 h apart, of ON 01210.Na (500 mg/kg) administered to male C3H/Hen mice (7-9 weeks) via SC injection or oral route. The dose response (100 to 750 mg/kg) and survival advantage of ON 01210.Na administered at 24 h and 15 min prior to 7.5 or 8 Gy whole body irradiation from a ¹³⁷Cs source (dose rate 1 Gy/min) were studied in these mice. Effects on the hematopoietic system were investigated by complete blood count and granulocyte-macrophage colony forming unit assay. A significant survival advantage and hematopoietic protection were observed after prophylactic oral ON 01210.Na and results were comparable to SC administration. These findings correlated well with pharmacokinetic data. Both SC and oral ON 01210.Na showed significant survival advantage against radiation toxicity and ON 01210.Na mediated hematopoietic protection plays key role in enhanced survival of mice. Oral administration holds better clinical promise as an effective countermeasure not only for early-responders in a nuclear accident, but also for the at-risk civilian population.     

Liver dysfunction after chemotherapy in lymphoma patients infected with hepatitis C

Reactivation of hepatitis B virus (HBV) infection in asymptomatic hepatitis B surface antigen carriers undergoing chemotherapy or immunosuppressive therapy is a well-documented complication. However, data on the consequence of chemotherapy on the course of hepatitis C virus (HCV) infection in HCV+ patients have been controversial. Here, we review the current knowledge about the complications related to HCV in lymphoma patients receiving chemotherapy/immunosuppressive therapy. Although less frequent than HBV, these complications occur in a subset of patients with mortality rates up to 45%. Therefore, baseline screening for HBV and HCV before initiation of chemotherapy is crucial. High-risk patients having chronic active hepatitis, high baseline HCV viral load, HBV co-infection and receiving cytotoxic drugs, corticosteroids and rituximab (particularly if combined) should be closely monitored for serum transaminase, bilirubin and HCV RNA levels.     

Most effective regimen of tranexamic acid in knee arthroplasty: a prospective randomized controlled study in 240 patients

Background  

The antifibrinolytic tranexamic acid reduces surgical blood loss, but studies have not identified an optimal regimen.     

Postoperative Flexion Analysis of 3 Rotating-platform Knee Designs

Rotating-platform knee implants have successively undergone modifications to improve postoperative flexion. The cruciate-sacrificing Low Contact Stress (LCS) implant (DePuy Orthopaedics, Inc, Warsaw, Indiana) was modified into the cruciate-substituting PFC Sigma RP (ΣRP) implant and further into the PFC Sigma RPF (ΣRPF) implant (DePuy Orthopaedics, Inc). The goal of this study was to determine whether these modifications improved postoperative flexion. Postoperative flexion at 2 years was compared against preoperative flexion with regard to the general demographics of each group.Statistical analysis showed that the pre- to postoperative flexion changes achieved by the ΣRP (14.6°) and the ΣRPF (2.9°) were better (P<.001) than that achieved by the LCS (-10.3°); however, between the ΣRP (14.6°) and the ΣRPF (2.9°), the change was statistically insignificant (P=.045). In subgroups with preoperative flexion less than 125°, postoperative flexion achieved was 100.1° with the LCS, 119.8° with the ΣRP, and 121.3° with the ΣRPF. The difference between the ΣRP and ΣRPF and the LCS was statistically significant (P<.001), but between the ΣRP and the ΣRPF was statistically insignificant (P=.621). In subgroups with preoperative flexion 125° or more, postoperative flexion was 125° with the LCS, 132° with the ΣRP, and 130° with the ΣRPF, with no significant difference between groups (P=.416). Both cruciate-substituting designs produced better postoperative flexion than the cruciate-sacrificing design. The ΣRP, despite less preoperative flexion (P=.004), achieved statistically better postoperative flexion than the LCS (P<.001). In subgroups with comparable preoperative flexion, no statistical difference in postoperative flexion was achieved by the ΣRP and the ΣRPF.     

Allogeneic hematopoietic stem cell transplantation versus hypomethylating agents in patients with myelodysplastic syndrome: A retrospective case–control study

Allogeneic stem cell transplantation (allo‐SCT) is the only potentially curative treatment for myelodysplastic syndrome (MDS). Recently, hypomethylating agents (HMAs) have been shown to improve survival in patients with high‐risk MDS. We conducted a retrospective case–control study to compare survival with these treatment modalities in patients with untreated MDS. Controls were identified using a departmental database and transplant patients were matched in at least three of the following five criteria: year of diagnosis, age, blast percentage, International Prognostic Scoring System cytogenetic risk, and time from diagnosis to treatment. Median overall survival (OS) was 26 and 25 months for, respectively, allo‐SCT [(n = 53); range, 2–210 months] and HMA [(n = 40); range, 2–98 months] (P = 0.89). Four‐year survival rates were 24 and 23% for allo‐SCT patients and the nontransplant cohort, respectively. Patients undergoing allo‐SCT after 2000 had longer median OS compared with those transplanted before 2000 (41 versus 7 months, P=0.001). These results would suggest that prospective studies are needed to delineate the timing and efficacy of allo‐SCT in the HMA era. Am. J. Hematol. 88:198–200, 2013. © 2012 Wiley Periodicals, Inc.     

Clofarabine,idarubicin, and cytarabine (CIA) as frontline therapy for patients ≤60 years with newly diagnosed acute myeloid leukemia

Clofarabine is a second generation nucleoside analogue with activity in adults with acute myeloid leukemia (AML). A phase I trial of clofarabine, idarubicin, and cytarabine (CIA) in relapsed and refractory AML had shown an overall response rate (ORR) of 48%. To explore this combination further, we conducted a phase II study of (CIA) in patients with newly diagnosed AML ≤60 years. Patients ≥18–60 years with AML and adequate organ function were enrolled. Induction therapy consisted of clofarabine (C) 20 mg m^?2 IV daily (days 1–5), idarubicin (I) 10 mg m^?2 IV daily (days 1–3), and cytarabine (A) 1 g m^?2 IV daily (days 1–5). Patients in remission received up to six consolidation cycles (C 15 mg m^?2 × 3, I 8 mg m^?2 × 2, and A 0.75 g m^?2 × 3). Fifty‐seven patients were evaluable. ORR was 79%. With a median follow up of 10.9 months, the median overall survival (OS) was not reached, the median event‐free survival (EFS) was 13.5 months. Most toxicities were ≤grade 2. Four week mortality was 2%. In subgroup analysis, patients ≤40 years had better OS (P = 0.04) and EFS (P = 0.04) compared to patients >40 years. Compared to historical patients treated with idarubicin and cyarabine (IA), the OS and EFS were significantly longer for CIA treated patients. In multivariate analysis, CIA retained its favorable impact on OS compared to IA. Thus, CIA is an effective and safe therapy for patients ≤60 years with newly diagnosed AML. Am. J. Heamtol. 88:961–966, 2013. © 2013 Wiley Periodicals, Inc.     

Prognostic impact of RAS mutations in patients with myelodysplastic syndrome

RAS is an oncogene frequently mutated in human cancer. RAS mutations have been reported in 10–15% of cases of acute myeloid leukemia (AML) but they appear to be less frequent among patients with myelodysplastic syndrome (MDS). The impact of RAS mutations in patients with MDS is unclear. We conducted a retrospective study in 1,067 patients with newly diagnosed MDS for whom RAS mutational analysis was available. Overall, 4% of patients carried mutant RAS alleles. Notably, FLT3 mutations, which were found in 2% of patients, were mutually exclusive with RAS mutations. Patients with RAS mutations had a higher white blood cell count as well as bone marrow blasts compared with patients carrying wild‐type RAS. However, no differences were observed between both groups regarding the risk of AML transformation (9% vs. 7%) and overall survival (395 days vs. 500 days, P = 0.057). In summary, RAS mutations are infrequent in patients with MDS and do not appear to negatively impact their outcome. Am. J. Hematol. 88:365–369, 2013. © 2013 Wiley Periodicals, Inc.