Exposure of juvenile skeletal muscle to a weightless environment reduces growth and satellite cell mitotic activity. However, the effect of a weightless environment on the satellite cell population during muscle repair remains unknown. Muscle injury was induced in rat soleus muscles using the myotoxic snake venom, notexin. Rats were placed into hindlimb-suspended or weightbearing groups for 10 days following injury. Cellular proliferation during regeneration was evaluated using 5-bromo-2'-deoxyuridine (BrdU) immunohistochemistry and image analysis. Hindlimb suspension reduced (P < 0.05) regenerated muscle mass, regenerated myofiber diameter, uninjured muscle mass, and uninjured myofiber diameter compared to weightbearing rats. Hindlimb suspension reduced (P < 0.05) BrdU labeling in uninjured soleus muscles compared to weight-bearing muscles. However, hindlimb suspension did not abolish muscle regeneration because myofibers formed in the injured soleus muscles of hindlimb-suspended rats, and BrdU labeling was equivalent (P > 0.10) on myofiber segments isolated from the soleus muscles of hindlimb-suspended and weightbearing rats following injury. Thus, hindlimb suspension (weightlessness) does not suppress satellite cell mitotic activity in regenerating muscles before myofiber formation, but reduces growth of the newly formed myofibers.
Varicella-zoster virus (VZV) reactivation is a relatively common cause of morbidity following autologous hematopoietic cell transplant (auto-HCT). The Centers for Disease Control in 2009 recommended extending VZV prophylaxis for 1 year post-transplantation. We retrospectively analyzed rates of VZV reactivation following auto-HCT at our transplant center prior to and after the implementation of extended antiviral prophylaxis in June 2008. The study population was divided into three different cohorts according to the length of VZV prophylaxis as following: (1) prophylaxis until neutrophil recovery to ≥500/μL (n = 77), (2) prophylaxis for 6 months (n = 12), or (3) 12 months (n = 40) post-auto-HCT. All patients received acyclovir 400 mg oral or intravenously twice daily or valacyclovir 500 mg oral daily. For patients in whom VZV reactivation occurred, data was collected on severity of infection, time of onset, treatment, and any associated complications. One hundred twenty-nine patients undergoing auto-HCT between January 1, 2004 and January 31, 2010 were included in the study. There was a significant difference in the rates of VZV reactivation between the neutrophil recovery and 12 months prophylaxis cohorts at 14 % (n = 11) and 2 % (n = 1) (P = 0.04), respectively. VZV reactivation rate in the 6-month prophylaxis group was 17 % (n = 2), but did not reach statistical significance due to small numbers. In the subset of auto-HCT patients treated with bortezomib, 13 % (n = 2) developed VZV reactivation in the neutrophil recovery group, while no events occurred in the other two cohorts. Complications of VZV reactivation include post-herpetic neuralgia (n = 5), severe pain (n = 3), scarring (n = 1), and motor weakness (n = 1); two patients required hospitalization and three patients developed disseminated zoster. Our limited retrospective analysis suggests a significant reduction in rates of post-auto-HCT rates of VZV reactivation with extended 12 months antiviral prophylaxis. VZV reactivation is a significant complication post-auto-HCT, and extended prophylaxis appears to be safe and effective in this setting.
Thirty-day readmission (30-DR) has become an important quality-of-care measure. Allogeneic hematopoietic cell transplantation (allo-HCT) presents a medical setting with higher readmission rates. We analyzed factors affecting 30-DR and its impact on patient outcomes and on health care costs in 91 patients who underwent reduced-toxicity conditioning (RTC) allo-HCT with fludarabine and busulfan. The patient cohort was divided into 2: the readmission group (R-gp) or the no-readmission group (NR-gp). Overall, 38% (n = 35) required readmission with a median time to readmission of 14 days. In multivariate analysis, only documented infection during the index admission predicted 30-DR, P =.01. With a median follow-up of 18 months (range, 1 to 69) for surviving patients, the 2-year overall survival was 49% and 58% in the R-gp and NR-gp respectively, P =.48. The 1-year nonrelapse mortality in R-gp and NR-gp was 18% and 13% respectively, P =.43. The median post-transplantation hospital charges in the R-gp and NR-gp were $85,115 (range, $32,015 to $242,519) and $45,083 (range, $10,715 to $485,456), P = .0002. In conclusion, only documented infections during the index hospitalization influenced 30-DR after RTC allo-HCT. Although 30-DR did not adversely affect mortality or survival, it was associated with significantly increased 100-day post-transplantation hospital charges, thus supporting its role as a quality-of-care measure in allo-HCT patients.
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