Long-term results of total elbow arthroplasty in patients with hemophilia.

HYPOTHESIS: It was hypothesized that the long-term survivorship and clinical outcome are reasonable, justifying total elbow arthroplasty (TEA) in patients with end-stage hemophilic arthropathy. METHODS: From 2002 to 2012, 13 primary TEAs (Coonrad-Morrey design) were implanted in 9 consecutive patients with an average age of 55 (range, 39-76) years. Type A hemophilia was diagnosed in 7 patients and type B hemophilia in 2 patients. Clinical and radiographic results of all (11 TEAs) but 1 patient were retrospectively analyzed. RESULTS: After a mean of 9.1 (range, 5-14) years, the mean visual analog scale score for pain, total Mayo Elbow Performance Score, and subjective elbow value were significantly improved from 5 (standard deviation, ±3) to 2 (±2; P = .007) points, from 64 (±16) to 89 (±11; P = .008) points, and from 47% (±15%) to 81% (±11%; P < .001), respectively. Whereas the flexion arc remained unchanged (P = .279), mean active pronation improved significantly (P = .024). Postoperative complications were recorded in 8 TEAs (62%), whereas 5 TEAs (38%) underwent partial component exchange after a mean of 7.2 (range, 3-10) years: 2 for periprosthetic infection, 2 for polyethylene wear, and 1 for humeral component loosening. Of the living patients after partial component exchange (n = 3), the mean final total Mayo Elbow Performance Score, flexion and rotation arc, visual analog scale score for pain, and subjective elbow value were comparable with the results of the living patients without revision surgery (n = 8). CONCLUSIONS: TEA for patients with advanced hemophilic arthropathy is associated with a substantial complication and revision rate. However, even after revision without implant removal, it provides good functional and subjective long-term results.

Long-term results of total knee arthroplasty in haemophilic patients: an 18-year follow-up.

PURPOSE: Total knee arthroplasty (TKA) for patients with end-stage haemophilic arthropathy is considered to be a successful procedure with satisfying mid- to long-term results. It was the purpose of this study to provide clinical and radiological long-term results of TKAs implanted in a consecutive cohort of haemophilic patients. METHODS: Primary TKA was performed in 43 consecutive knees in 30 haemophilic patients. After a mean of 18 (SD ± 4) years, 15 patients (21 knees) with a mean age of 58 (SD ± 8) years were available for follow-up. The outcome was assessed using the Knee Society score, WOMAC, SF-36, Kaplan-Meier survivorship analysis as well as radiographic evaluation of radiolucency. RESULTS: In 13 (30%) of the 43 consecutive knees, revision surgery was necessary due to infection or aseptic loosening, among which eight (19%) due to aseptic loosening and five (12%) due to haematogenous infection. The calculated 20-year survival rates with revision for any reason or infection as the end points were 59 and 82%, respectively. All patients with the primary TKA in situ observed progressive radiolucent lines around the implants at the final follow-up. The Knee Society clinical and functional score significantly improved from pre- (36 points; SD ± 16 and 62 points; SD ± 19) to post-operatively (73 points; SD ± 15 and 78 points; SD ± 18; p < 0.001). Eighty-six per cent rated their result as either good or excellent. Whereas flexion did not improve, flexion contracture could be reduced significantly from 18° (SD ± 12) to 6° (SD ± 5; p < 0.001) post-operatively. CONCLUSION: Total knee arthroplasty in haemophilic patients is associated with high revision, loosening and infection rates after 18 years. However, if revision can be avoided, joint replacement in haemophilic patients helps to relieve pain, achieve higher subjective satisfaction and to restore knee function. Level of evidence IV.

A genome-wide association study of resistance to HIV infection in highly exposed uninfected individuals with hemophilia A.

Human genetic variation contributes to differences in susceptibility to HIV-1 infection. To search for novel host resistance factors, we performed a genome-wide association study (GWAS) in hemophilia patients highly exposed to potentially contaminated factor VIII infusions. Individuals with hemophilia A and a documented history of factor VIII infusions before the introduction of viral inactivation procedures (1979-1984) were recruited from 36 hemophilia treatment centers (HTCs), and their genome-wide genetic variants were compared with those from matched HIV-infected individuals. Homozygous carriers of known CCR5 resistance mutations were excluded. Single nucleotide polymorphisms (SNPs) and inferred copy number variants (CNVs) were tested using logistic regression. In addition, we performed a pathway enrichment analysis, a heritability analysis, and a search for epistatic interactions with CCR5 Δ32 heterozygosity. A total of 560 HIV-uninfected cases were recruited: 36 (6.4%) were homozygous for CCR5 Δ32 or m303. After quality control and SNP imputation, we tested 1 081 435 SNPs and 3686 CNVs for association with HIV-1 serostatus in 431 cases and 765 HIV-infected controls. No SNP or CNV reached genome-wide significance. The additional analyses did not reveal any strong genetic effect. Highly exposed, yet uninfected hemophiliacs form an ideal study group to investigate host resistance factors. Using a genome-wide approach, we did not detect any significant associations between SNPs and HIV-1 susceptibility, indicating that common genetic variants of major effect are unlikely to explain the observed resistance phenotype in this population.

Haemophilic knee arthropathy: long-term outcome after total knee replacement.

PURPOSE: The objective of this study was to evaluate the long-term outcome and prosthetic survival of primary total knee arthroplasty in haemophilic patients. It was hypothesized that the infection and revision rate are higher and the outcome inferior when compared with patients without haemophilia. METHODS: Between 1985 and 2004, forty-three consecutive primary total knee replacements were performed in thirty haemophilic patients. These patients' charts were reviewed retrospectively. Twenty-five patients (34 knees) were available for clinical and radiological follow-up. The outcome was assessed using the Knee Society score, WOMAC and Kaplan-Meier survivorship analysis. RESULTS: An haematogenous infection occurred in two patients. In three patients, component revision was needed: two because of an infection and one because of a mechanical failure. After a mean follow-up of 9.6 years (2-20), 94% of the patients rated their result as either excellent or good. At time of follow-up, the Knee Society Score averaged 73.3 points (range, 29-100) and showed a significant gain (p < 0.001) compared to preoperative. Flexion contracture could be reduced significantly (p < 0.001) from 18.1° preoperatively to 8.4° at follow-up, whereas flexion remained unchanged. When infection or any component replacement was set as endpoints, the 10 years prosthetic survival was 90 and 86%, respectively. CONCLUSION: Total knee arthroplasty in haemophilic patients is a reliable treatment that results in pain relief and functional improvement with a low risk of postoperative infection. However, neither the postoperative infection rate nor the functional result does reach the same level as in a population not affected by haemophilia. LEVEL OF EVIDENCE: IV.

Immunosuppressive treatment for acquired haemophilia: current practice and future directions in Germany, Austria and Switzerland.

Acquired haemophilia is an autoimmune disorder characterised by autoantibody formation against coagulation factor VIII. Immunosuppressive treatments including steroids, cytotoxic drugs, rituximab or combinations thereof have been used to eradicate autoantibodies. Very few prospective studies exist evaluating the use of these treatments. Here, we performed a survey among 73 physicians from 57 haemophilia treatment centres in order to describe current practice patterns and critical issues for future research in acquired haemophilia. The results demonstrate a high diversity of first- and second-line treatments. Factors influencing treatment decision were underlying disorder, severity of bleeding and inhibitor titre. Frequently used first-line treatments were steroids plus cyclophosphamide (44%) and steroids alone (11%). Second-line treatment was most often rituximab (30%), with or without steroids and/or cyclophosphamide. Most participants indicated to change from first- to second-line treatment after 4 weeks in case of failure to obtain partial remission (31%), continued bleeding (40%) or continued severe bleeding requiring bypass treatment (59%). Immunoadsorption was preferred for first- and second-line treatment by 10% and 9% of participants, respectively. These results highlight critical issues in the field. Open questions and directions for future research are discussed.

Epstein-Barr virus DNA in serum in a HIV-infected patient during development and treatment of non-Hodgkin's lymphoma.

Immunocompromised patients are at risk of developing Epstein-Barr virus (EBV)-related lymphoproliferative disorders. Quantitative determination of serum EBV DNA permits early diagnosis of an AIDS-related non-Hodgkin's lymphoma, and surveillance of treatment response and/or relapse, and thus may be a useful tool to monitor disease activity.

Entomologic and serologic evidence of zoonotic transmission of Babesia microti, eastern Switzerland.

We evaluated human risk for infection with Babesia microti at a site in eastern Switzerland where several B. microti-infected nymphal Ixodes ricinus ticks had been found. DNA from pooled nymphal ticks amplified by polymerase chain reaction was highly homologous to published B. microti sequences. More ticks carried babesial infection in the lower portion of the rectangular 0.7-ha grid than in the upper (11% vs. 0.8%). In addition, we measured seroprevalence of immunoglobulin (Ig) G antibodies against B. microti antigen in nearby residents. Serum from 1.5% of the 396 human residents of the region reacted to B. microti antigen (>1:64), as determined by indirect immunofluorescence assay (IgG). These observations constitute the first report demonstrating B. microti in a human-biting vector, associated with evidence of human exposure to this agent in a European site.