Thu Jul 02 11:40:38 PDT 2009
McKee MD, Veillette CJ, Hall JA, Schemitsch EH, Wild LM, McCormack R, Perey B, Goetz T, Zomar M, Moon K, Mandel S, Petit S, Guy P, Leung I, 2009 Jan-Feb. "A multicenter, prospective, randomized, controlled trial of open reduction--internal fixation versus total elbow arthroplasty for displaced intra-articular distal humeral fractures in elderly patients."
J Shoulder Elbow Surg 18 (1): 3-12
[PubMed]
Abstract:
We conducted a prospective, randomized, controlled trial to compare functional outcomes, complications, and reoperation rates in elderly patients with displaced intra-articular, distal humeral fractures treated with open reduction-internal fixation (ORIF) or primary semiconstrained total elbow arthroplasty (TEA). Forty-two patients were randomized by sealed envelope. Inclusion criteria were age greater than 65 years; displaced, comminuted, intra-articular fractures of the distal humerus (Orthopaedic Trauma Association type 13C); and closed or Gustilo grade I open fractures treated within 12 hours of injury. Both ORIF and TEA were performed following a standardized protocol. The Mayo Elbow Performance Score (MEPS) and Disabilities of the Arm, Shoulder and Hand (DASH) score were determined at 6 weeks, 3 months, 6 months, 12 months, and 2 years. Complication type, duration, management, and treatment requiring reoperation were recorded. An intention-to-treat analysis and an on-treatment analysis were conducted to address patients randomized to ORIF but converted to TEA intraoperatively. Twenty-one patients were randomized to each treatment group. Two died before follow-up and were excluded from the study. Five patients randomized to ORIF were converted to TEA intraoperatively because of extensive comminution and inability to obtain fixation stable enough to allow early range of motion. This resulted in 15 patients (3 men and 12 women) with a mean age of 77 years in the ORIF group and 25 patients (2 men and 23 women) with a mean age of 78 years in the TEA group. Baseline demographics for mechanism, classification, comorbidities, fracture type, activity level, and ipsilateral injuries were similar between the 2 groups. Operative time averaged 32 minutes less in the TEA group (P = .001). Patients who underwent TEA had significantly better MEPSs at 3 months (83 vs 65, P = .01), 6 months (86 vs 68, P = .003), 12 months (88 vs 72, P = .007), and 2 years (86 vs 73, P = .015) compared with the ORIF group. Patients who underwent TEA had significantly better DASH scores at 6 weeks (43 vs 77, P = .02) and 6 months (31 vs 50, P = .01) but not at 12 months (32 vs 47, P = .1) or 2 years (34 vs 38, P = .6). The mean flexion-extension arc was 107 degrees (range, 42 degrees -145 degrees) in the TEA group and 95 degrees (range, 30 degrees -140 degrees) in the ORIF group (P = .19). Reoperation rates for TEA (3/25 [12%]) and ORIF (4/15 [27%]) were not statistically different (P = .2). TEA for the treatment of comminuted intra-articular distal humeral fractures resulted in more predictable and improved 2-year functional outcomes compared with ORIF, based on the MEPS. DASH scores were better in the TEA group in the short term but were not statistically different at 2 years' follow-up. TEA may result in decreased reoperation rates, considering that 25% of fractures randomized to ORIF were not amenable to internal fixation. TEA is a preferred alternative for ORIF in elderly patients with complex distal humeral fractures that are not amenable to stable fixation. Elderly patients have an increased baseline DASH score and appear to accommodate to objective limitations in function with time.
Cil A, Veillette CJ, Sanchez-Sotelo J, Morrey BF, 2008. "Linked elbow replacement: a salvage procedure for distal humeral nonunion."
J Bone Joint Surg Am 90 (9): 1939-50
[PubMed]
Abstract:
BACKGROUND: Nonunion is a challenging and not uncommon complication of distal humeral fractures. Our long-term experience with linked semiconstrained total elbow arthroplasty as a salvage procedure for patients with distal humeral nonunion not amenable to internal fixation was investigated. METHODS: Ninety-one consecutive patients (ninety-two elbows) underwent total elbow arthroplasty for the treatment of a distal humeral nonunion, and the results were reviewed at a mean of 6.5 years postoperatively. Patients' charts and anteroposterior and lateral radiographs made prior to and immediately after the joint replacement and at the time of the latest follow-up were reviewed to identify intraoperative and postoperative complications, and radiographic evidence of loosening or bushing wear. The outcome measures consisted of prosthetic survival, with implant removal as the end point for failure, and the Mayo Elbow Performance Score (MEPS). RESULTS: At the time of the most recent follow-up, joint stability had been initially restored in all patients, including nine who had had a grossly flailed elbow. Sixty-seven (74%) of the patients had no pain or mild pain at the time of the latest follow-up, whereas seventy-nine patients (87%) had had moderate or severe pain prior to the surgery. While 85% (seventy-seven) of the ninety-one patients rated the outcome as better or much better, twenty patients (22%) had a fair or poor MEPS. A total of forty-four complications occurred in forty elbows, and there were thirty-two reoperations, twenty-three of which involved implant revision or removal. Factors that increased the risk of implant failure were a patient age of less than sixty-five years, two or more prior surgical procedures, and a history of infection. The rate of prosthetic survival without removal or revision for any reason was 96% at two years, 82% at five years, and 65% at both ten and fifteen years. CONCLUSIONS: Linked semiconstrained total elbow arthroplasty is a salvage procedure that can provide pain relief and restore motion and function in patients with a distal humeral nonunion that is not amenable to internal fixation. Substantial risk factors for failure include an age of less than sixty-five years, multiple previous surgical procedures, and any history of infection.
Veillette CJ, Steinmann SP, 2008. "Olecranon fractures."
Orthop Clin North Am 39 (2): 229-36, vii
[PubMed]
Abstract:
Approximately 10% of fractures about the adult elbow consist of fractures of the olecranon process of the ulna and range from simple nondisplaced fractures to complex fracture-dislocations of the elbow. Several treatment options for internal fixation have been described, including tension-band wiring, plate fixation, intramedullary screw fixation, and triceps advancement after fragment excision. The method of internal fixation is chosen based primarily on fracture type. Because olecranon fractures are all intra-articular injuries, they require anatomic or essentially normal surface reduction and trochlear notch contour for predictable outcomes. In addition, fixation must be stable enough to permit early mobilization to avoid significant elbow stiffness. Given the variability in fracture patterns, the complex anatomy, and associated injuries, treating surgeons must be familiar with multiple treatment methods and follow a systematic surgical strategy to avoid complications and achieve reliable outcomes.
Veillette CJ, McKee MD, 2007. "Growth factors--BMPs, DBMs, and buffy coat products: are there any proven differences amongst them?"
Injury 38 Suppl 1: S38-48
[PubMed]
Abstract:
Advances in the understanding of bone repair and improved biotechnology have led to the introduction of new strategies for orthopedic surgeons to control and modulate bone healing using growth factors. However, many orthopedic surgeons are uncertain about the current levels of evidence supporting the use of materials that possess these properties and their therapeutic role in the management of skeletal problems such as fracture, long-bone nonunion, and spine fusion. In particular, the differences amongst osteoinductive factors synthesized by recombinant gene technology, or derived from demineralized bone matrix or platelet rich plasma requires clarification.
, 2007. "Nonoperative treatment compared with plate fixation of displaced midshaft clavicular fractures. A multicenter, randomized clinical trial."
J Bone Joint Surg Am 89 (1): 1-10
[PubMed]
Abstract:
BACKGROUND: Recent studies have shown a high prevalence of symptomatic malunion and nonunion after nonoperative treatment of displaced midshaft clavicular fractures. We sought to compare patient-oriented outcome and complication rates following nonoperative treatment and those after plate fixation of displaced midshaft clavicular fractures. METHODS: In a multicenter, prospective clinical trial, 132 patients with a displaced midshaft fracture of the clavicle were randomized (by sealed envelope) to either operative treatment with plate fixation (sixty-seven patients) or nonoperative treatment with a sling (sixty-five patients). Outcome analysis included standard clinical follow-up and the Constant shoulder score, the Disability of the Arm, Shoulder and Hand (DASH) score, and plain radiographs. One hundred and eleven patients (sixty-two managed operatively and forty-nine managed nonoperatively) completed one year of follow-up. There were no differences between the two groups with respect to patient demographics, mechanism of injury, associated injuries, Injury Severity Score, or fracture pattern. RESULTS: Constant shoulder scores and DASH scores were significantly improved in the operative fixation group at all time-points (p = 0.001 and p < 0.01, respectively). The mean time to radiographic union was 28.4 weeks in the non-operative group compared with 16.4 weeks in the operative group (p = 0.001). There were two nonunions in the operative group compared with seven in the nonoperative group (p = 0.042). Symptomatic malunion developed in nine patients in the nonoperative group and in none in the operative group (p = 0.001). Most complications in the operative group were hardware-related (five patients had local irritation and/or prominence of the hardware, three had a wound infection, and one had mechanical failure). At one year after the injury, the patients in the operative group were more likely to be satisfied with the appearance of the shoulder (p = 0.001) and with the shoulder in general (p = 0.002) than were those in the nonoperative group. CONCLUSIONS: Operative fixation of a displaced fracture of the clavicular shaft results in improved functional outcome and a lower rate of malunion and nonunion compared with nonoperative treatment at one year of follow-up. Hardware removal remains the most common reason for repeat intervention in the operative group. This study supports primary plate fixation of completely displaced midshaft clavicular fractures in active adult patients.
Veillette CJ, Mehdian H, Schemitsch EH, McKee MD, 2006. "Survivorship analysis and radiographic outcome following tantalum rod insertion for osteonecrosis of the femoral head."
J Bone Joint Surg Am 88 Suppl 3: 48-55
[PubMed]
Abstract:
BACKGROUND: For early stages of osteonecrosis, preservation of the femoral head is the primary objective; however, there has not been a consensus on how best to achieve this goal. Core decompression alone is associated with a lack of structural support with inconsistent outcomes, whereas vascularized fibular grafting requires an extensive surgical procedure with high donor-site morbidity and prolonged rehabilitation. The adjunctive use of a porous tantalum implant offers the advantages of core decompression, structural support, minimally invasive surgery, and no donor-site morbidity. The purpose of this study was to assess the survivorship and to evaluate the clinical results and radiographic outcomes of hips in which osteonecrosis of the femoral head was treated with core decompression and a porous tantalum implant. METHODS: We evaluated fifty-four patients (sixty consecutive hips) in whom osteonecrosis of the femoral head was treated with core decompression and insertion of a porous tantalum implant. Fifty-two patients (fifty-eight hips) were available for follow-up at a mean of twenty-four months. All patients were sixty-five years of age or younger (mean age, thirty-five years). According to the classification system of Steinberg et al., one hip (2%) had stage-I disease, forty-nine hips (84%) had stage-II disease, and eight hips (14%) had stage-III disease. Outcome measures that were used included a limb-specific score (Harris hip score), radiographic outcome measures, and survivorship analysis with revision to total hip arthroplasty as the end point. RESULTS: Overall, nine hips (15.5%) were converted to total hip arthroplasty, including six with stage-II disease and three with stage-III disease. The overall survival rates were 91.8% (95% confidence interval, 87.8% to 95.8%) at twelve months, 81.7% (95% confidence interval, 75.8% to 87.6%) at twenty-four months, and 68.1% (95% confidence interval, 54.7% to 81.5%) at forty-eight months. The absence of chronic systemic diseases resulted in a survival rate of 92% at forty-eight months (95% confidence interval, 87.4% to 96.4%). CONCLUSIONS: Treatment of early stage osteonecrosis of the femoral head with core decompression and a porous tantalum implant can be accomplished with a minimally invasive technique and no donor-site morbidity. The early clinical results show encouraging survival rates in patients who do not have chronic systemic disease, especially in association with early stage disease. LEVEL OF EVIDENCE: Therapeutic Level IV. See Instructions to Authors on jbjs.org for a complete description of levels of evidence.
Veillette CJ, von Schroeder HP, 2004. "Endothelin-1 down-regulates the expression of vascular endothelial growth factor-A associated with osteoprogenitor proliferation and differentiation."
Bone 34 (2): 288-96
[PubMed]
Abstract:
Endothelin-1 (ET-1) is implicated in the signaling between vascular endothelial cells (VECs) and osteoblasts during bone development, remodeling and repair. Vascular endothelial growth factor (VEGF) also plays an important role in these intercellular interactions. Our objectives were to identify which specific VEGF isoforms were produced during osteoblastic proliferation and differentiation and to determine the effects of ET-1 on VEGF mRNA and protein production by osteoblastic cells. Semiquantitative reverse transcription polymerase chain reaction (RT-PCR) and ELISA were used to evaluate VEGF mRNA isoform expression and protein synthesis at different stages of ET-1-induced osteoblastic differentiation in fetal rat calvaria (FRC) osteoblastic cells. Three VEGF mRNA isoforms were identified corresponding to VEGF(120), VEGF(164) and VEGF(188). Predominant isoforms VEGF(120) and VEGF(164) had a bimodal expression that increased in the early proliferation and late mineralization phases. ET-1 stimulated osteoblastic proliferation and differentiation, but surprisingly, ET-1 down-regulated VEGF mRNA and protein expression and sustained the down-regulation over time in long-term cultures. Time course studies showed that ET-1 inhibited VEGF mRNA expression after incubation for 3 h in 7- and 14-day FRC cell cultures. Similarly, ET-1 inhibited VEGF protein secretion by 5.8- and 2.8-fold in 7- and 14-day FRC cells, respectively. VEGF-A protein secretion was inhibited by ET-1 in a dose-dependent manner with a maximal effect at 10(-7) M. This study supports a novel inhibitory role for ET-1 on VEGF synthesis in osteoblastic cells as a feedback mechanism in the temporal and spatial coupling of angiogenesis to bone formation and resorption.
von Schroeder HP, Veillette CJ, Payandeh J, Qureshi A, Heersche JN, 2003. "Endothelin-1 promotes osteoprogenitor proliferation and differentiation in fetal rat calvarial cell cultures."
Bone 33 (4): 673-84
[PubMed]
Abstract:
Endothelin-1 (ET-1), a peptide produced by vascular endothelial cells, has been suggested to be one of the signaling factors between vascular and osteoblastic cells during bone growth and remodeling. The osteoinductive effects of ET-1 were tested on fetal rat calvaria which have the ability to form bone nodules in culture. ET-1 (10(-10) to 10(-6) M) dose-dependently increased cell proliferation. The effect of ET-1 (10(-8) M) on proliferation was greater than that of dexamethasone (Dex; 10(-8) M). ET-1 also increased the number of bone nodules by 146% over untreated cells, which coincided with a 3.1-fold increase in alkaline phosphatase activity. Limiting dilution assays showed that ET-1 treatment increased the number of osteoprogenitors (CFU-AP and CFU-OB) beyond what would be expected by a proliferative effect alone, indicating that ET-1 also stimulated osteoblast differentiation. Osteocalcin mRNA expression was upregulated as shown by Northern blot analysis. Using cDNA microarray analysis, ET-1 treatment resulted in an expression profile that included an upregulation of 163 genes and expressed sequence tags. Simultaneous addition of ET-1 and Dex to the medium further increased the number of bone nodules and alkaline phosphatase activity over either treatment alone. Our results show that ET-1 promotes both osteoblastic proliferation and differentiation and that the effects of ET-1 and Dex on differentiation are cooperative.
Chan DW, Ye R, Veillette CJ, Lees-Miller SP, 1999. "DNA-dependent protein kinase phosphorylation sites in Ku 70/80 heterodimer."
Biochemistry 38 (6): 1819-28
[PubMed]
Abstract:
Ku antigen is composed of 70 and 82 kDa subunits (Ku70 and Ku80, respectively) that together bind with high affinity to ends of double-stranded DNA and other DNA structures in vitro. When bound to DNA, the Ku 70/80 heterodimer enhances the kinase activity of the catalytic subunit of the DNA-dependent protein kinase, DNA-PKcs. Ku and DNA-PKcs are required for V(D)J recombination and DNA double-strand break repair in vivo and may also play a role in regulation of transcription. Ku is phosphorylated by DNA-PKcs in vitro, and cells that lack DNA-PKcs are deficient in Ku phosphorylation in vitro, suggesting that Ku may be a physiological target for DNA-PK. Here we have identified the sites of DNA-PK phosphorylation in human Ku protein. We find that Ku70 is phosphorylated at a single serine residue, serine 6, located in the putative transcriptional activation domain, and Ku80 is phosphorylated at serines 577 and 580 and at threonine 715. Interestingly, none of the phosphorylation sites identified in Ku correspond to the serine-glutamine consensus for DNA-PK phosphorylation, consistent with previous reports that DNA-PK can recognize additional phosphorylation motifs.
Veillette CJ, Cunningham KD, Hart DA, Fritzler MJ, Frank CB, 1998. "Localization and characterization of porcine patellar tendon xenograft antigens in a rabbit model of medial collateral ligament replacement."
Transplantation 65 (4): 486-93
[PubMed]
Abstract:
BACKGROUND: Ligament injuries of the knee are common and, if severe, can predispose to joint pain, instability, reinjury, and, ultimately, osteoarthritis. Xenograft replacement of ligaments could have potential; however, a limited understanding of the immunology of ligament xenograft rejection has inhibited their use. The purpose of this study was to characterize the antigenic elements of a fresh porcine tendon xenograft in a rabbit model and to provide a better understanding of what would need to be done to either block or extract these antigenic elements. METHODS: Three experimental situations were evaluated in a pig to rabbit ligament transplantation model: subcutaneous implantation of fresh porcine patellar tendon (PPT), implantation of fresh PPT into a medial collateral ligament midsubstance gap, and replacement of the entire medial collateral ligament complex with either fresh or guanidinium hydrochloride-extracted PPT. Preimmune and immune sera were collected from rabbits and used to localize antigenic targets in PPT, meniscus, and cartilage with indirect immunofluorescence techniques. The reactivities of the same rabbit sera towards tissue extracts of PPT, meniscus, and cartilage by Western immunoblot analyses were used to characterize the antigenic components. RESULTS: Indirect immunofluorescence with preimmune rabbit sera on PPT showed staining of tendon fibroblasts. Immune sera from rabbits transplanted with xenografts stained regions of the extracellular matrix of PPT. Fresh PPT induced antibodies that consistently recognized six extracellular matrix components with molecular masses of >200 kDa, 180 kDa, 135 kDa, 108 kDa, 63 kDa, and 59 kDa. CONCLUSIONS: Our results suggest that naturally occurring rabbit anti-pig antibodies of the IgG isotype recognize immunogenic components on tendon fibroblasts, whereas induced rabbit anti-pig antibodies recognize a specific subset of six extracellular matrix components of PPT. PPT xenografts appeared to induce a similar humoral immune response irrespective of graft location. Finally, our results indicate that selective extraction of PPT xenograft components before implantation altered the induced rabbit anti-pig antibody response; however, such extraction did not change the ultimate fate of the transplant tissue.
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