Early Results in Total Replacement of the Distal Radioulnar Joint.

BACKGROUND: Pathology of the distal radioulnar joint (DRUJ) including instability and arthritis presents a challenge for hand and upper extremity surgeons. Surgical options include a Darrach procedure and similar resections, soft tissue interposition arthroplasty, and a one-bone forearm. In 2005, a prosthesis for DRUJ arthroplasty was approved for use in the United States. The authors hypothesize that DRUJ arthroplasty will lead to improved pain and range of motion (ROM) with a moderate, but manageable, complication rate. METHODS: A retrospective review of 46 patients who underwent DRUJ arthroplasty by a single private group of hand surgeons was performed. Demographics, complications, postoperative visual analog scale (VAS), and postoperative ROM were obtained and analyzed. RESULTS: The patients were followed up for a mean of 60 weeks. The implant was used both as primary surgical treatment for DRUJ pathology and as salvage for previous failed procedures. Twenty-two percent of patients experienced complications: 15% required revision surgery. No patients were converted to another type of implant, including those who underwent revision surgery. Prominent hardware was the most common indication requiring revision. Patients achieved an improvement in supination of 17° and extension of 5°. They additionally achieved a decrease in average VAS score from 7.1 to 2.3. CONCLUSIONS: Distal radioulnar joint arthroplasty reduces pain and improves ROM in patients with DRUJ pathology with a 22% complication rate. This cohort demonstrates improved pain, modest improvement in ROM, but a 22% complication rate for this implant. Further long-term studies are encouraged.

Return to Sports and Recreational Activities Following Arthroplasty of the Basal Joint of the Thumb: A Retrospective Review.

Purpose: Arthroplasty of the basal, or carpometacarpal, joint of the thumb has been shown to decrease pain, improve strength, improve range of motion, and allow return to work. This study sought to assess whether basal joint arthroplasty also allows for a return to sports and recreational activities. Methods: A survey assessing participation in sports and recreational activities, timing of return to play after surgery, enjoyment, and the presence of pain and limitations was mailed to patients who had undergone an arthroplasty of the basal joint of the thumb over a 3-year period. Results: Of the 333 patients who underwent thumb carpometacarpal arthroplasty, met the criteria, and responded, 73% were able to successfully return to sports and recreational activities, with decreased pain and at the same or increased level of play, frequency of participation, and level of enjoyment for their sport or recreational activity. Patients were more likely to successfully return to sports and recreational activities if they had undergone surgery on their nondominant hand, did not stop their sport or recreational activity before surgery, were able to return within 9 months of surgery, and reported no postoperative limitations. Successful return to sports and recreational activities was not related to age, sex, surgeon, level of play, or the type of sport or recreational activity. Conclusions: Most patients who replied to our survey reported successful return to sports and recreational activities after arthroplasty of the basal joint of the thumb. Type of study/level of evidence: Prognostic IV.

Double complex mutations involving F8 and FUNDC2 caused by distinct break-induced replication.

Genomic rearrangements are a well-recognized cause of genetic disease and can be formed by a variety of mechanisms. We report a complex rearrangement causing severe hemophilia A, identified and further characterized using a range of PCR-based methods, and confirmed using array-comparative genomic hybridization (array-CGH). This rearrangement consists of a 15.5-kb deletion/16-bp insertion located 0.6 kb from a 28.1-kb deletion/263-kb insertion at Xq28 and is one of the most complex rearrangements described at a DNA sequence level. We propose that the rearrangement was generated by distinct but linked cellular responses to double strand breakage, namely break-induced replication (BIR) and a novel model of break-induced serial replication slippage (SRS). The copy number of several genes is affected by this rearrangement, with deletion of part of the Factor VIII gene (F8, causing hemophilia A) and the FUNDC2 gene, and duplication of the TMEM185A, HSFX1, MAGEA9, and MAGEA11 genes. As the patient exhibits no clinically detectable phenotype other than hemophilia A, it appears that the biological effects of the other genes involved are not dosage-dependent. This investigation has provided novel insights into processes of DNA repair including BIR and the first description of SRS during repair in a pathological context.

A prospective study of recombinant activated factor VII administered by continuous infusion to inhibitor patients undergoing elective major orthopaedic surgery: a pharmacokinetic and efficacy evaluation.

After surgery in haemophilia, haemostasis is difficult to maintain in the presence of an antifactor VIII antibody. This study assessed the pharmacokinetics of recombinant activated factor VII (rFVIIa) and its efficacy in securing post-operative haemostasis in haemophiliacs with inhibitors. Continuous infusion of rFVIIa was evaluated for elective major orthopaedic surgery in nine patients with neutralizing antibodies to FVIII and at high risk of bleeding. After an initial preoperative bolus of 90 micro g/kg, rFVIIa was infused at a fixed rate of 50 micro g/kg/h for a median of 20 d (range 7-20 d). The median plasma FVII coagulant activity (FVII:C) at 24 h, 72 h and 20 d after surgery was 38 IU/ml (range 22-169 IU/ml), 45 IU/ml (range 17-88 IU/ml) and 31 IU/ml (range 27-46 IU/ml) respectively. The median plasma FVIIa:C at the same time points was 51 (range 24-211), 63 (range 22-99) and 44 (range 28-76) IU/ml respectively. Median total rFVIIa clearance remained stable during the rFVIIa continuous infusion period and was 40 (range 9-70), 34 (range 17-86) and 48 (range 32-55)ml/kg/h at the end of 24 h, 72 h and 20 d infusion respectively. Post-operatively, there were bleeds in six patients, which settled readily after a single bolus of rFVIIa (60 micro g/kg). There was a good clinical outcome for all patients. These data indicate that rFVIIa infusion at 50 micro g/kg/h achieves continuous plasma FVII procoagulant activity in excess of 30 IU/ml (12-15 nmol/l) and provides adequate haemostatic control for inhibitor patients during major orthopaedic surgery.

Evidence for a role for Galphai1 in mediating weak agonist-induced platelet aggregation in human platelets: reduced Galphai1 expression and defective Gi signaling in the platelets of a patient with a chronic bleeding disorder.

We have examined platelet functional responses and characterized a novel signaling defect in the platelets of a patient suffering from a chronic bleeding disorder. Platelet aggregation responses stimulated by weak agonists such as adenosine diphosphate (ADP) and adrenaline were severely impaired. In comparison, both aggregation and dense granule secretion were normal following activation with high doses of collagen, thrombin, or phorbol-12 myristate-13 acetate (PMA). ADP, thrombin, or thromboxane A2 (TxA2) signaling through their respective Gq-coupled receptors was normal as assessed by measuring either mobilization of intracellular calcium, diacylglycerol (DAG) generation, or pleckstrin phosphorylation. In comparison, Gi-mediated signaling induced by either thrombin, ADP, or adrenaline, examined by suppression of forskolin-stimulated rise in cyclic AMP (cAMP) was impaired, indicating dysfunctional Galphai signaling. Immunoblot analysis of platelet membranes with specific antiserum against different Galpha subunits indicated normal levels of Galphai2,Galphai3,Galphaz, and Galphaq in patient platelets. However, the Galphai1level was reduced to 25% of that found in normal platelets. Analysis of platelet cDNA and gDNA revealed no abnormality in either the Galphai1 or Galphai2 gene sequences. Our studies implicate the minor expressed Galphai subtype Galphai1 as having an important role in regulating signaling pathways associated with the activation of alphaIIbbeta3 and subsequent platelet aggregation by weak agonists.