Does prophylactic sotalol and magnesium decrease the incidence of atrial fibrillation following coronary artery bypass surgery: a propensity-matched analysis

Background  

Atrial fibrillation can occur in up to 40% of patients undergoing coronary surgery.     

Retention of "safe" blood donors. The Retrovirus Epidemiology Donor Study

BACKGROUND: There are obvious advantages to increasing donor retention. However, for reasons of blood safety, certain donors may, in fact, be more desirable to retain than others. “Safe” donors are defined as those who provided a blood donation that was negative on all laboratory screening tests and who subsequently reported no behavioral risks in response to an anonymous survey. This study identifies the most important factors affecting the intention of “safe” donors to provide another donation. STUDY DESIGN AND METHODS: An anonymous survey asking about donation history, sexual history, injecting drug use, and recent donation experience was mailed to 50,162 randomly selected allogeneic donors (including directed donors) who gave blood from April through July or from October through December 1993 at one of the five United States blood centers participating in the Retrovirus Epidemiology Donor Study. Before mailing, questionnaires were coded to designate donors with nonreactive laboratory screening tests at their most recent donation. RESULTS: A total of 34,726 donors (69%) responded, with substantially higher response among repeat donors. According to reported intentions only, the vast majority of “safe” donors indicated a high likelihood of donating again within the next 12 months. Only 3.4 percent reported a low likelihood of donating again. A comparison of those likely to return and those unlikely to return reveals significant differences in demographics and in ratings of the donation experience. A higher proportion of those unlikely to return were first-time donors, minority-group donors, and donors with less education. The highest projected loss among “safe” donors was seen for those who gave a fair to poor assessment of their treatment by blood center staff or of their physical well-being during or after donating. CONCLUSION: These data suggest that efforts to improve donors' perceptions of their donation experience, as well as attention to the physical effects of blood donation, may aid in the retention of both repeat and first-time donors.     

Systemic lupus erythematosus after renal transplantation: patient and graft survival and disease activity. The Dutch Working Party on Systemic Lupus Erythematosus

OBJECTIVE: To determine the outcome of renal transplantation in patients with systemic lupus erythematosus and end-stage renal failure and to compare disease activity after transplantation with disease activity before transplantation. DESIGN: Retrospective case finding using data for an 8-year period from the central registry for renal replacement therapy in The Netherlands. SETTING: Tertiary care hospitals with facilities for renal transplantation in the Netherlands. PATIENTS: Twenty-eight patients who fulfilled at least four of the American Rheumatology Association's criteria for the classification of systemic lupus erythematosus and who received a renal transplant. MEASUREMENTS: Actuarial survival rates for grafts and patients after transplantation, maximal nonrenal scores on the Systemic Lupus Erythematosus Disease Activity Index, and time-adjusted disease exacerbation rates in all patients before and after transplantation. RESULTS: The actuarial graft survival rate at 1 year and 5 years was 68% (95% CI, 47% to 82%) and 54% (CI, 25% to 77%), respectively, whereas the actuarial patient survival rate was 87% (CI, 69% to 96%) at 1 and 5 years. High disease activity was not found to affect graft survival adversely before the start of renal replacement therapy or during dialysis. After transplantation, disease activity per patient and the overall incidence of disease exacerbations decreased. One case of recurrent lupus nephritis was seen. CONCLUSIONS: Patients with systemic lupus erythematosus and end-stage renal failure are excellent candidates for renal transplantation; disease activity after transplantation is sporadic and low, and the recurrence of lupus nephritis is rare.     

Mutation spectrum and genotype-phenotype analyses in Cowden disease and Bannayan-Zonana syndrome, two hamartoma syndromes with germline PTEN mutation

The tumour suppressor gene PTEN , which maps to 10q23.3 and encodes a 403 amino acid dual specificity phosphatase (protein tyrosine phosphatase; PTPase), was shown recently to play a broad role in human malignancy. Somatic PTEN deletions and mutations were observed in sporadic breast, brain, prostate and kidney cancer cell lines and in several primary tumours such as endometrial carcinomas, malignant melanoma and thyroid tumours. In addition, PTEN was identified as the susceptibility gene for two hamartoma syndromes: Cowden disease (CD; MIM 158350) and Bannayan-Zonana (BZS) or Ruvalcaba-Riley-Smith syndrome (MIM 153480). Constitutive DNA from 37 CD families and seven BZS families was screened for germline PTEN mutations. PTEN mutations were identified in 30 of 37 (81%) CD families, including missense and nonsense point mutations, deletions, insertions, a deletion/insertion and splice site mutations. These mutations were scattered over the entire length of PTEN , with the exception of the first, fourth and last exons. A 'hot spot' for PTEN mutation in CD was identified in exon 5 that contains the PTPase core motif, with 13 of 30 (43%) CD mutations identified in this exon. Seven of 30 (23%) were within the core motif, the majority (five of seven) of which were missense mutations, possibly pointing to the functional significance of this region. Germline PTEN mutations were identified in four of seven (57%) BZS families studied. Interestingly, none of these mutations was observed in the PTPase core motif. It is also worthy of note that a single nonsense point mutation, R233X, was observed in the germline DNA from two unrelated CD families and one BZS family. Genotype-phenotype studies were not performed on this small group of BZS families. However, genotype-phenotype analysis inthe group of CD families revealed two possible associations worthy of follow-up in independent analyses. The first was an association noted in the group of CD families with breast disease. A correlation was observed between the presence/absence of a PTEN mutation and the type of breast involvement (unaffected versus benign versus malignant). Specifically and more directly, an association was also observed between the presence of a PTEN mutation and malignant breast disease. Secondly, there appeared to be an interdependent association between mutations upstream and within the PTPase core motif, the core motif containing the majority of missense mutations, and the involvement of all major organ systems (central nervous system, thyroid, breast, skin and gastrointestinal tract). However, these observations would need to be confirmed by studying a larger number of CD families.      

Anti-heparan sulphate reactivity in sera from patients with systemic lupus erythematosus with renal or non-renal manifestations.

Previously, we have shown that anti-DNA can bind to heparan sulphate (HS), a constituent of the glomerular basement membrane (GBM). We hypothesized that binding of anti-DNA to HS in the GBM plays a role in the onset of systemic lupus erythematosus (SLE) nephritis. To test this hypothesis we measured the anti-HS reactivity in cross-sectional and longitudinal studies of SLE patients with or without nephritis. In the transverse serum study single serum samples from 26 SLE patients were studied. We found no correlation between anti-HS reactivity and previously development of nephritis (anti-HS positive: seven out of 16 with history of nephritis, two out of 10 without nephritis). However, six of the seven anti-HS positive sera in the nephritis group were obtained within 1 month of the onset of nephritis, suggesting a temporal relationship between anti-HS reactivity and onset of nephritis. In the longitudinal serum study between six and 16 serum samples were studied from each of 10 SLE-patients. In five out of five episodes of nephritis we found anti-HS reactivity before the onset or exacerbation of the nephritis. In four non-renal manifestations anti-HS reactivity was found in only one episode; in none of the three patients who remained clinically stable did serum samples show anti-HS reactivity. Anti-HS reactivity was only found in sera positive for anti-DNA by Farr assay but the anti-HS titre was not a mere reflection of the reactivity measured in the Farr assay. This indicates that only a subpopulation of anti-DNA can bind to HS. We found a high correlation (r = 0.99) between anti-HS reactivities in plasma and serum and we conclude that anti-HS reactivity in serum samples from SLE patients is not due to in vitro complex formation during clotting. Although further prospective analysis is necessary, our data suggest that measurement of anti-HS reactivity in SLE patients might identify patients at risk for the development of nephritis.     

Rheumatoid factor by laser nephelometry and Waaler-Rose assay: prognostic value in patients with recent-onset rheumatoid arthritis

OBJECTIVE: To evaluate the prognostic value of rheumatoid factor (RF), detected in the Waaler-Rose agglutination assay and by nephelometry, in patients with recent-onset rheumatoid arthritis (RA). METHODS: Consecutive patients with new-onset RA between 1993 and 1997 were followed for a median period of 4.7 years. Clinical data at baseline and drug use during the disease course were recorded. Outcome parameters studied were disease process, damage (erosions, joint surgery, extra-articular manifestations, and new co-morbidity), and death. Cut-off levels for RF were >40 IU/mL (nephelometry) and titres 1:160 (Waaler-Rose haemagglutination). RESULTS: RF tests were negative by both methods in 22% of RA patients (RF- group), while 33% were RF positive by nephelometry only (RF+ group) and 45% were positive by Waaler-Rose and nephelometry (RF++ group). Baseline clinical and laboratory findings as well as the number of subsequently used disease-modifying anti-rheumatic drugs (DMARDs), the number of patients starting and the time spent on steroid therapy were similar in the three RF groups. Odd ratios for death (n = 23), erosions (n = 62), and serious extra-articular disease manifestations (EAMs) (n = 13) as well as patient survival, erosion-free or surgery-free survival rates did not differ between the RF groups. Only rheumatoid nodules were more frequent in RF++ patients. CONCLUSION: The baseline presence of RF by either Waaler-Rose or nephelometry was not associated with differences in drug therapy, morbidity other than rheumatoid nodules, or mortality in RA patients in the first 5 years of disease. Being immunoglobulin M (IgM) RF positive thus had little impact on RA patient outcome.     

Recurrence of primary sclerosing cholangitis after liver transplantation is associated with specific changes in the gut microbiome pretransplant – a pilot study

Primary sclerosing cholangitis (PSC) is a common indication for liver transplantation (LT). Up to 25% of patients experience recurrence of PSC (rPSC) after LT, which is associated with significant morbidity and mortality. To date, it is not possible to predict which patients are at risk for rPSC. The aetiology of PSC is complex and is speculated to involve translocation of intestinal bacteria to the liver, because of its frequent co-occurrence with inflammatory bowel diseases (IBD). Here, we investigate whether the mucosal intestinal microbiome of PSC patients (n = 97) at time of first LT can identify those patients who will develop rPSC. 16S gene sequencing of bacterial DNA isolated from formalin-fixed paraffin-embedded biopsies showed that PSC patients with Crohn’s disease (n = 15) have a reduced microbial diversity and that inflammation of the mucosa is associated with beta-diversity changes and feature differences. No differences in alpha- or beta diversity were observed between patients with rPSC (n = 14) and without rPSC (n = 83). However, many over-represented bacterial features were detected in patients with rPSC, while surprisingly, those without recurrence of disease were characterized by an increased presence of the Gammaproteobacteria Shigella. This pilot study warrants further investigation into bacterial differences between rPSC and non-rPSC patients.