Prognostic value of beta-thromboglobulin in patients with transient cerebral ischaemia

Plasma levels of beta-thromboglobulin (BTG) and fibrinopeptide A (FPA), markers of platelet alpha-granule release and thrombin generation respectively, were measured in 27 subjects with transient cerebral ischaemic attacks (TIA), 43 age-matched controls, and 32 young controls. BTG and FPA were both higher in elderly controls than in young controls. BTG was higher in TIA subjects than in age-matched controls and higher in the 12 TIA subjects who had further vascular events in the next year than in those who had no further events. FPA was not significantly associated with TIA or with further events. These results support a relationship between platelet activation and TIA and suggest that BTG levels indicate a group at higher risk of further vascular events.     

The degree of matching at HLA-DPB1 predicts for acute graft-versus-host disease and disease relapse following haematopoietic stem cell transplantation

The importance of matching for HLA-DPB1 in unrelated donor haematopoietic stem cell (HSC) transplantation is little understood. Most transplant centres do not, currently, prospectively match for DPB1, but emerging data show that DPB1 matching does play a role in determining outcome. We studied the impact of HLA-DPB1 matching on outcome in 143 recipients of T-cell depletion transplants, who matched with their respective unrelated donors (allelic level) at HLA-A, -B, -C, -DRB1 and -DQB1. Of those matched at DPB1, 47.2% (17/36) developed acute graft-versus-host disease (aGvHD) as compared to 66.3% (55/83) of those who were mismatched. This led to a 19.1% (95% CI 0.1-38.3%) increase in the chance of developing aGvHD in mismatched patients (P=0.049). Relapse of the original disease occurred in 51 recipients; 23 of 37 (62%) matched at both DPB1 alleles, 28 of 82 (34%) were mismatched at one or two DPB1 alleles. Thus, there was a significantly higher relapse rate (P=0.0011) in transplant recipients who matched at both DPB1 alleles. In conclusion, a donor/recipient DPB1 match was associated with a significantly lower incidence of aGvHD and a significantly higher incidence of disease relapse. This study provides further evidence for an immunogenic role of HLA-DPB1 in HSC transplants.     

Oral antifungals as prophylaxis in haematological malignancy

In the standard treatment of patients with haematological malignancy, immunosuppressive therapy produces prolonged periods of neutropenia and mucositis, which increase the risk of systemic fungal infection. In allogeneic bone marrow transplantation, this risk extends well beyond the period of neutropenia when graft-versus-host disease, and its treatment, result in prolonged lymphocytopenia. Various agents are used for antifungal prophylaxis and treatment but all have limitations: amphotericin B is restricted by the need for intravenous infusion and the occurrence of adverse events, fluconazole by its narrow spectrum of activity and the emergence of fluconazole-resistant fungi and itraconazole capsules by erratic absorption. Oral administration of antifungals has clear advantages in prophylaxis and an important current strategy is to maximize the extent and reliability of the oral bioavailability of antifungal agents. Mucositis is the main obstacle for success of strategies based on oral delivery. In this review, the ability of these new oral formulations to deliver sufficient antifungal prophylaxis is evaluated.     

The significance of host haemopoietic cells detected by cytogenetic analysis of bone marrow from recipients of bone marrow transplants

Bone marrow from 39 patients who received a bone marrow transplant (BMT) from a matched donor of different sex were studied by chromosome analysis for evidence of mixed haemopoietic chimaerism (MC). Recipient metaphases were detected in the bone marrow of 10 patients after BMT. Patients in whom MC was detected within 6 weeks of BMT did not all have a poor outcome. Two of seven are disease-free survivors at greater than 470 and greater than 632 d. All three patients in whom MC was diagnosed more than 6 weeks after BMT subsequently relapsed. Four factors appear to be important in determining the probability of relapse when MC is detected in a patient after BMT: the timing of detection of residual recipient cells; the proportion of these cells in the bone marrow; persistence of these cells in increasing proportions; and the karyotype of the recipient metaphases detected. Cytogenetic assessment may provide the earliest indication of relapse in these patients. In addition, this study provides further evidence that cyclophosphamide and total body irradiation, as used in these patients, may be inadequate conditioning therapy for BMT.     

The Effects of Calcium Supplementation on Verified Coronary Heart Disease Hospitalization and Death in Postmenopausal Women: A Collaborative Meta‐Analysis of Randomized Controlled Trials

Calcium supplementation, particularly with vitamin D, has been an approved public health intervention to reduce fracture risk. Enthusiasm for this intervention has been mitigated by meta‐analyses suggesting that calcium supplementation with or without vitamin D increases myocardial infarction (MI) risk; however, concern has been raised over the design of these meta‐analyses. We, therefore, undertook a meta‐analysis of randomized controlled trials with placebo or no‐treatment control groups to determine if these supplements increase all‐cause mortality and coronary heart disease (CHD) risk including MI, angina pectoris and acute coronary syndrome, and chronic CHD verified by clinical review, hospital record, or death certificate in elderly women. The Cochrane Central Register of Controlled Trials, MEDLINE, and EMBASE databases were searched from January 1, 1966, to May 24, 2013, for potentially eligible studies, reference lists were checked, and trial investigators were contacted where additional unpublished data were required. The search yielded 661 potentially eligible reports of which 18 met the inclusion criteria and contributed information on 63,563 participants with 3390 CHD events and 4157 deaths. Two authors extracted the data independently with trial data combined using random‐effects meta‐analysis to calculate the relative risk (RR). Five trials contributed CHD events with pooled relative RR of 1.02 (95% confidence interval [CI], 0.96–1.09; p = 0.51). Seventeen trials contributed all‐cause mortality data with pooled RR of 0.96 (95% CI, 0.91–1.02; p = 0.18). Heterogeneity among the trials was low for both primary outcomes (I² = 0%). For secondary outcomes, the RR for MI was 1.08 (95% CI, 0.92–1.26; p = 0.32), angina pectoris and acute coronary syndrome 1.09 (95% CI, 0.95–1.24; p = 0.22) and chronic CHD 0.92 (95% CI, 0.73–1.15; p = 0.46). In conclusion, current evidence does not support the hypothesis that calcium supplementation with or without vitamin D increases coronary heart disease or all‐cause mortality risk in elderly women. © 2014 American Society for Bone and Mineral Research.