No abstract

Induction therapy with daclizumab safely reduces the frequency and severity of cardiac-allograft rejection during the induction period.

Background-Cardiac transplantation vasculopathy is the leading cause of late death in heart transplantation recipients.Rapamycin is an immunosuppressant drug with potent antiproliferative and antimigratory effects. We investigated whether rapamycin could prevent progression of graft vasculopathy in 46 patients (age, 54Ϯ10 years; 4.3Ϯ2.3 years after transplantation) with severe disease. Methods and Results-At annual cardiac catheterization, patients were randomly assigned to treatment with rapamycin (nϭ22) versus continued current immunosuppression (nϭ24). Clinical characteristics including recipient age and sex, underlying cause of congestive heart failure, donor age and sex, and ischemic time were recorded. Cardiac catheterization was graded with the use of a semiquantitative scale and repeated annually. Clinically significant adverse events were defined as death, need for angioplasty or bypass surgery, myocardial infarction, and a Ͼ25% worsening of the catheterization score. These events were monitored as primary study end points. Anti-HLA class I and II antibody production and lymphocyte growth assays were measured with each biopsy. Patients selected for rapamycin had azathioprine or mycophenolate mofetil discontinued and were given rapamycin. Outcomes were compared by means of log-rank analysis. There were no significant differences in baseline characteristics. Duration of follow-up was comparable (rapamycin, 689Ϯ261; control, 630Ϯ207 days; NS). In the rapamycin group, 3 patients reached primary end points versus 14 patients in the control group (PϽ0.001). There was no difference in baseline or subsequent anti-HLA class I or II antibody production. Conclusions-In

These results emphasize the importance of specifically screening heart transplantation candidates for the presence of IgG antibodies directed against MHC class II molecules and suggest that strategies aimed at their reduction may have an impact on the onset and frequency of high-grade cellular rejections after transplantation.

No abstract

Uncontrolled studies have suggested that bone marrow-derived mesenchymal stem cells (MSCs) may be effective against acute graft-versus-host disease (aGVHD). We conducted a multicenter, randomized study to assess the efficacy of using ex vivo cultured adult human MSC (remestemcel-L) in addition to second-line therapy to treat steroid-refractory aGVHD (NCT00366145). In total, 260 patients, 6 months to 70 years of age, were enrolled from August 2006 to May 2009 and were randomized 2:1 to receive 8 intravenous infusions of remestemcel-L or placebo, given over 4 weeks, in addition to second-line therapy according to institutional standards. Four additional infusions over 4 weeks were indicated for patients with incomplete response at day 28. Randomization was stratified by aGVHD grade. Efficacy and safety were assessed through 180 days of follow-up, with the primary endpoint being durable complete response (DCR), defined as complete resolution of aGVHD symptoms for any period of at least 28 days after beginning treatment. Remestemcel-L did not meet the primary endpoint of greater DCR in the intent-to-treat population (35% versus 30%; P = 0.42). In post hoc analyses, patients with liver involvement who received at least 1 infusion of remestemcel-L had a higher DCR, and higher overall complete or partial response rate (OR) than those who received placebo (29% versus 5%; P = .047). Among high-risk patients (aGVHD grades C and D), remestemcel-L demonstrated significantly higher OR at day 28 than placebo (58% versus 37%; P = 0.03). Furthermore, pediatric patients had a higher OR with MSCs compared with placebo (64% versus 23%; P = .05). Similar rates of adverse events were observed between treatment groups. Remestemcel-L was safe and well tolerated. Results of this study did not demonstrate superior DCR compared with placebo when added to standard of care. The favorable clinical responses seen in some patient subsets may warrant further investigation.

No abstract

The 12-month clinical outcomes of nursing home patients who underwent videofluoroscopic swallowing evaluation was determined. A retrospective review of 40 patients in a teaching nursing home who had videofluoroscopic swallowing studies from 1987 through 1989 was performed. Clinical outcomes measured included feeding tube placement, rehospitalization within 1 year, prolonged nursing home stay (> 6 months), pneumonia, and pneumonia death. It was determined if outcomes were associated with the presence of aspiration on videofluoroscopy and subsequent feeding tube placement. In the 12-month follow-up period, 17 of 40 patients (43%) who underwent videofluoroscopic swallowing evaluation developed pneumonia and 18 of 40 (45%) died. Twenty-two patients demonstrated aspiration on videofluoroscopy. Increased rehospitalization was the only outcome measure that was associated with the presence of aspiration on videofluoroscopy (p < or = 0.05). Of 22 patients with aspiration, 15 had feeding tubes placed. This group had a higher rate of pneumonia (p < or = 0.05) and pneumonia death (p < or = 0.05) compared with the 7 patients with aspiration who did not receive feeding tubes. Patients with nasogastric tubes had a higher death rate (7/9) than patients with gastrostomy tubes (2/8; p < or = 0.05), but similar rates of rehospitalization and pneumonia. Nursing home patients who underwent video-fluoroscopic swallowing evaluation had poor clinical outcomes at 12 months, regardless of their test results.(ABSTRACT TRUNCATED AT 250 WORDS)