Tantalum in type IV and V Paprosky periprosthetic acetabular fractures surgery in Paprosky type IV and V periprosthetic acetabular fractures surgery.

PURPOSE: Periprosthetic acetabular fractures represent a growing and serious complication of total hip arthroplasty (THA). The purpose of the study is to report our experience in the use of tantalum for the treatment of Paprosky type IV and V periprosthetic acetabular fractures. METHOD: We analyzed 24 patients with type IV and V periprosthetic acetabular fractures. Patients were treated with a revision surgery using tantalum components, in some cases in association with posterior plating. Outcomes were evaluated using VAS, Harris hip score and considering the average time of integration of the acetabulum and the number of complications. The endpoint evaluation was established at 24 months. RESULT: Results show that the average time of integration of the neoacetabulum in tantalum was 12.3 months (range 6-18 months). The average VAS pain is 8.7/10 cm at time 0 and gradually returns to basic pre-injury values in the following months. The average value of HHS at time 0 is 13.5 points. This value tends to increase progressively until reaching a mean score of 89.3 points at 24 months, higher than the average pre-trauma value of 84.3 points. CONCLUSION: Periprosthetic fractures of the acetabulum with bone loss are a rare but potentially disastrous complication of total hip prostheses. Their management and therapeutic choice will test the ability of the orthopedic surgeon. It is important to determine the type of fracture and characteristics in order to pursue an adequate therapeutic strategy. The modern biomaterials, such as porous tantalum, offer a greater potential in replacing bone loss, promoting bone regrowth and obtaining a stable implant.

The challenge of non-union in subtrochanteric fractures with breakage of intramedullary nail: evaluation of outcomes in surgery revision with angled blade plate and allograft bone strut.

PURPOSE: Subtrochanteric fractures have a bimodal age distribution. They usually require open reduction and internal fixation. Closed reduction and intramedullary nail fixation rate are increased for this type of fracture. As a result, the hardware breakage and non-union rate is high among such patients. Our purpose is to evaluate the outcomes of the role of blade plate and bone strut allograft in the management of subtrochanteric non-union by femoral nailing. MATERIALS AND METHODS: We reported a group of 22 patients with subtrochanteric non-union, associated with breakage of the intramedullary nail with medial femoral allograft bone and lateral blade plate and wire (PS) s; and a group of 13 patients with subtrochanteric non-union, associated with breakage of the intramedullary nail treated with lateral blade plate and screws (CG). The chosen criteria to evaluate the two group during the clinical and radiological follow-up were the quality of life, measured by The Short Form (12) Health Survey (SF-12), the hip function and quality of life related to it, measured by the Harris Hip Score (HHS), bone healing, measured by Radiographic Union Score (RUS) by XR and CT at 1 year after the surgery, and postoperative complications. The evaluation endpoint was set at 12 months. RESULTS: The Bone healing measured by RUS occurred and also the full recovery before the first trauma measured by SF-12 and HHS are better in PS group. We only had three unimportant complications in PS while four breakage hardware in CG. CONCLUSION: We conclude that in complicated non-unions, the use of blade plate and bone strut allograft has a definite positive role in the management of such cases.

Enhanced fixation with hydroxyapatite coated pins.

Three groups of seven patients had external fixation of middiaphyseal tibial fractures using uncoated pins, uncoated bicylindrical pins, and hydroxyapatite coated bicylindrical pins, respectively. All fractures were fixed with six pins, and all fractures united. Median pin insertion torque was 0.6, 1.2, and 1.3 Nm in the three groups, respectively. Median extraction torque was 0.1, 0.1, and 2.1 Nm, respectively. Both types of stainless steel pins showed a lower extraction torque than insertion torque in all cases, whereas the mean extraction torque in the hydroxyapatite coated pins was unchanged. Seven of the 14 patients receiving uncoated pins had pin tract infection, compared with none of the patients receiving hydroxyapatite coated pins. Hydroxyapatite coating of external fixation pins increases stability and thereby reduces the risk for pin tract infection and mechanical failure of fracture fixation.

Interferon-gamma suppresses T-cell proliferation to mitogen via the nitric oxide pathway during experimental acute graft-versus-host disease.

The development of graft-versus-host disease (GVHD) is associated with long-lasting and profound deficits in immune function that lead to increased morbidity and mortality after bone marrow transplantation (BMT). We investigated a mechanism of T-cell immunodeficiency in response to mitogen or alloantigen in an experimental model of acute GVHD by analyzing the roles of two immunosuppressive moieties: interferon gamma (IFN-gamma) and nitric oxide (NO). Splenocytes from mice with GVHD did not proliferate either to the T-cell mitogen, concanavalin A (Con A), or to host alloantigens, but only mitogen-activated cultures produced increased levels of NO. The abrogation of NO synthesis with LG-mono-methyl-arginine (NMMA) restored mitogen-induced proliferation but not the response to host antigens. The mechanism of impared proliferation to mitogen was dependent on IFN-gamma because blockade of this cytokine in culture inhibited NO production and restored proliferation to Con A to levels similar to those in transplanted control mice without GVHD. NMMA did not substantially reduce IFN-gamma levels, demonstrating that NO acted distally to IFN-gamma in the pathway of immunosuppression in response to mitogen. Furthermore, the prevention of IFN-gamma production in vivo after allogeneic BMT, by transplantation of polarized type 2 donor T cells (secreting interleukin-4 but not IFN-gamma), also prevented NO production and restored splenocyte responses to mitogen. Our data demonstrate the existence of NO-dependent and NO-independent pathways involved in suppression of T-cell proliferation during acute GVHD. Excess NO synthesis appears to be one mechanism by which IFN-gamma induces immunodeficiency after allogeneic BMT.

Suppression of B-cell proliferation to lipopolysaccharide is mediated through induction of the nitric oxide pathway by tumor necrosis factor-alpha in mice with acute graft-versus-host disease.

Graft-versus-host disease (GVHD) is associated with impaired B-cell responses. We investigated the mechanism of impaired proliferation of B cells in response to the mitogen lipopolysaccharide (LPS) by analyzing the production of tumor necrosis factor-alpha (TNF-alpha) and nitric oxide (NO), both of which have independently been described as important effector mechanisms in the pathogenesis of acute GVHD. A threefold decrease of mature surface Ig-positive (slg+) B cells was observed in GVHD spleens isolated 2 weeks after transplant. However, proliferation of these cells in response to LPS was suppressed by more than 35-fold. Activated GVHD splenocytes secreted large amounts of TNF-alpha and NO in culture. Neutralization of TNF-alpha with anti-TNF-alpha antibody (Ab) both abrogated NO production and restored LPS-induced proliferation of B cells to levels found in non-GVHD control mice. The specific inhibition of NO synthesis with LG-monomethyl-arginine (NMMA) restored splenocyte responses but did not significantly reduce TNF-alpha levels, showing that TNF-alpha per se did not cause immunosuppression. These data show that, during GVHD, induction of the NO pathway is an important mechanism that mediates B-cell hyporesponsiveness to LPS and that this pathway is induced by TNF-alpha.

Polarized type 2 alloreactive CD4+ and CD8+ donor T cells fail to induce experimental acute graft-versus-host disease.

Acute graft-vs-host disease (GVHD) is thought to be mediated by alloreactive T cells with a type 1 cytokine phenotype. To prevent the development of acute GVHD, we have successfully polarized mature donor T cells toward a type 2 cytokine phenotype ex-vivo by incubating them with murine rIL-4 in a primary MLC. Polarized type 2 T cells were then transplanted with T cell-depleted bone marrow cells into irradiated recipients across either MHC class II (bm12-->C57BL/6) or class I (bm1-->C57BL/6) barriers, and the intensity of GVHD was measured by assessment of several in vitro and in vivo parameters. The injection of polarized type 2 T cells abrogated the mitogen-induced production of IFN-gamma by splenocytes from transplanted hosts on day 13 after bone marrow transplantation (BMT). Injection of polarized type 2 T cells failed to induce secretion of the effector phase cytokine TNF-alpha by splenocytes stimulated with LPS both in vitro and in vivo, and survival of transplanted mice after i.v. injection with LPS was significantly improved. Furthermore, cell-mixing experiments revealed that polarized type 2 T cells were able to inhibit type 1 cytokine responses induced by naive T cells after BMT. These data demonstrate that both polarized CD4+ and CD8+ type 2 alloreactive donor T cells can be generated in vitro from mature T cell populations. These cells function in vivo to inhibit type 1 T cell responses, and such inhibition attenuates the systemic morbidity of GVHD after BMT across both MHC class II or class I barriers in mice.

Recombinant human interleukin-1 receptor antagonist in the treatment of steroid-resistant graft-versus-host disease.

Acute graft-versus-host disease (GVHD) that is resistant to therapy is a highly lethal complication of marrow transplantation. Inflammatory cytokines such as interleukin-1 (IL-1) may be critical mediators of this process. If so, specific inhibition of IL-1 activity with recombinant human IL-1 receptor antagonist (IL-1Ra), a naturally occurring competitive inhibitor of IL-1, may ameliorate acute GVHD. We performed an open-label, phase I/II trial to evaluate the safety and efficacy of IL-1Ra in 17 patients with steroid-resistant GVHD. The IL-1Ra was administered as a 24-hour continuous infusion over 7 days. The dose was escalated in cohorts of patients from 400 to 3,200 mg/d. Acute GVHD was evaluated in each affected organ and as an overall grade. Stage-specific improvement of acute GVHD occurred in the skin (8 of 14, 57%), gut (9 of 11, 82%), and liver (2 of 11, 18%). Overall, acute GVHD improved by at least one grade in 10 of 16 (63%) patients. Response to therapy was associated with a reduction of tumor necrosis factor-alpha (TNF-alpha) mRNA levels in blood mononuclear cells (P = .001). The only toxicity attributable to IL-1Ra was reversible transaminase elevation in two patients. Inhibition of IL-1 activity with IL-1Ra is safe and has demonstrable efficacy in acute GVHD that failed to respond to conventional treatment. These data provide further evidence that IL-1 is a mediator of GVHD.