Allogeneic hematopoietic SCT for alpha-mannosidosis: an analysis of 17 patients

Alpha-mannosidosis is a rare lysosomal storage disease. Hematopoietic SCT (HSCT) is usually recommended as a therapeutic option though reports are anecdotal to date. This retrospective multi institutional analysis describes 17 patients that were diagnosed at a median of 2.5 (1.1-23) years and underwent HSCT at a median of 3.6 (1.3-23.1) years. In all, 15 patients are alive (88%) after a median follow-up of 5.5 (2.1-12.6) years. Two patients died within the first 5 months after HSCT. Of the survivors, two developed severe acute GvHD (>=grade II) and six developed chronic GvHD. Three patients required re-transplantation because of graft failure. All 15 showed stable engraftment. The extent of the patients' developmental delay before HSCT varied over a wide range. After HSCT, patients made developmental progress, although normal development was not achieved. Hearing ability improved in some, but not in all patients. We conclude that HSCT is a feasible therapeutic option that may promote mental development in alpha-mannosidosis.     

Identification by random forest method of HLA class I amino acid substitutions associated with lower survival at day 100 in unrelated donor hematopoietic cell transplantation

The identification of important amino acid substitutions associated with low survival in hematopoietic cell transplantation (HCT) is hampered by the large number of observed substitutions compared with the small number of patients available for analysis. Random forest analysis is designed to address these limitations. We studied 2107 HCT recipients with good or intermediate risk hematological malignancies to identify HLA class I amino acid substitutions associated with reduced survival at day 100 post transplant. Random forest analysis and traditional univariate and multivariate analyses were used. Random forest analysis identified amino acid substitutions in 33 positions that were associated with reduced 100 day survival, including HLA-A 9, 43, 62, 63, 76, 77, 95, 97, 114, 116, 152, 156, 166 and 167; HLA-B 97, 109, 116 and 156; and HLA-C 6, 9, 11, 14, 21, 66, 77, 80, 95, 97, 99, 116, 156, 163 and 173. In all 13 had been previously reported by other investigators using classical biostatistical approaches. Using the same data set, traditional multivariate logistic regression identified only five amino acid substitutions associated with lower day 100 survival. Random forest analysis is a novel statistical methodology for analysis of HLA mismatching and outcome studies, capable of identifying important amino acid substitutions missed by other methods.     

Coronary Stent Infections: A Case Report and Literature Review

Although rare, coronary artery stent infections are associated with a high mortality rate. Since the introduction of coronary stents in 1987, only 16 cases of infection have been reported. We report a new case in a 66-year-old woman who had undergone a difficult percutaneous coronary intervention procedure, during which 3 overlapping stents were implanted in the mid portion of the right coronary artery. Twenty-two days after the procedure, the patient died. Autopsy revealed the cause of death to be pericardial tamponade due to rupture of the right ventricular myocardium. The stented portion of the right coronary artery was enveloped by an abscess, and purulent material completely occluded the stents. Cultures of the myocardium were positive for methicillin-resistant Staphylococcus aureus. We conducted a review of the literature on coronary artery stent infections. Data suggest that early-onset infections (<10 days after stent implantation) are potentially amenable to medical therapy alone, but late-onset infections (≥10 days after implantation) or major complications necessitate combined surgical and medical therapy. Medical therapy consists of broad-spectrum antibiotics. Surgical intervention includes stent removal if possible, and abscess drainage or perforation repair when indicated.Key words: Blood vessel prosthesis implantation/adverse effects, coronary stent infections, prosthesis-related infections/complications/diagnosis/therapy, stents/adverse effects, Staphylococcus aureusCoronary artery stents have been in use for more than 2 decades. Stent infections are rare, hard to treat, and potentially devastating. Our treatment of a patient with a coronary stent abscess prompted us to review the literature. From our experience and the evaluation of previously reported cases,^1–14 we propose an approach for diagnosing and treating these infections.