Titanium, chromium and cobalt ions modulate the release of bone-associated cytokines by human monocytes/macrophages in vitro.

Osteolysis has become a major cause of aseptic loosening in total joint arthroplasty (TJA). Titanium, cobalt and chromium are commonly used in orthopaedic implants (e.g. joint prostheses). The release of bone-associated cytokines has been associated with the development of osteolysis in patients with prostheses. We evaluated the effects of these metals on the release of bone-associated cytokines (IL-1 beta, IL-6, TNF-alpha and TGF-beta 1) by human blood monocytes/macrophages and monocyte-like U937 cells upon lipopolysaccharide (LPS) stimulation, the cell proliferation, and their cytotoxic effects on these cells in vitro. We found that the release of IL-1 beta was enhanced by titanium, chromium and cobalt, the release of TNF-alpha was enhanced by titanium and chromium, and the release of IL-6 was enhanced by titanium. All three metal ions inhibited the release of TGF-beta 1. We also found that titanium and chromium, but not cobalt, enhanced blood monocyte/macrophage proliferation in response to LPS while only titanium enhanced U937 cell proliferation in response to LPS. The metals in concentrations ranging from 0.01 to 100 ngml-1 did not stimulate the cells to secrete detectable cytokines in the absence of LPS. Furthermore, a 4-h pre-exposure of blood monocytes/macrophages or U937 cells to the metals did not alter cytokine release when the metals were removed from the media prior to the addition of LPS. Similarly, a 4-h pre-exposure of blood monocytes/macrophages or U937 cells to LPS did not alter cytokine release when LPS was removed from the media prior to the addition of the metals. The metals did not reduce cell viability and induce cell injury after 72h incubation with the cells. The data suggest that the three metals at clinically relevant concentrations modulated cytokine expression, whereas they did not induce any cytotoxic effects. A metal-induced enhancement of bone-resorbing cytokine release with a concomitant inhibition of bone-forming cytokine release may be an important factor in the development of osteolysis, which can severely compromise the outcome of TJA.

Combined orthopedic and vascular injury in the lower extremities: indications for amputation.

A retrospective review was undertaken to determine risk factors associated with amputation after open fractures of the lower extremity that were complicated by vascular injury. During an 11-year period ending in December 1987, we observed open fractures in 31 patients and injuries to the popliteal artery in 16 patients, to the tibial arteries in eight patients, to the femoral artery in five patients, and to the dorsal artery of the foot in two patients. Vascular repair was accomplished in 25 patients; 12 patients had primary end-to-end anastomosis, 12 patients had reverse saphenous vein grafts, and one patient had a bovine graft. Of these 25 patients, five patients required amputation because of infection and three patients required amputation because of continued ischemia. Three patients with irreparable damage had immediate amputation, and three patients without distal ischemia had vessel ligation only. The risk factors associated with amputation were shock on admission (10 of 19 patients [p less than 0.02]) and a crushed extremity (10 of 18 patients [p less than 0.01]). The overall amputation rate, which included three immediate amputations and eight late amputations, was 35.2%. The data suggest that limb salvage is possible in two thirds of patients with combined orthopedic and vascular injuries of the lower extremity, but a history of shock or crush injury with vascular compromise is an unfavorable prognostic sign.

Use of antimicrobials in the management of open fractures.

The role of antibiotic therapy in open fractures is secondary to adequate debridement, irrigation, and definitive wound care. Experimental and clinical studies indicate that parenteral administration of appropriate antibiotics within three hours after injury helps to prevent wound sepsis. Intial wound cultures of 158 open fracture wounds revealed bacterial growth in 70.3%. Eighty-six were Gram-positive, 57 were Gram-negative, and 32 yielded mixed bacterial growth. Sensitivity studies of these organisms suggest that cephalothin sodium is the most effective antibiotic for prophylaxis. In a prospective study from 1969 to 1975, treatment of 520 patients was as follows: debridement, copious irrigation, and primary closure for types 1 and 2 fractures and secondary closure for type 3 fractures. No primary internal fixation was done except in vascular injuries. Cultures were taken of all wounds and antibiotics were given before surgery and for three days postoperatively. In type 3 open fractures, severe soft tissue injury, and segmental or traumatic amputation, the infection rate was 9%, compared to a 44% infection rate in the retrospective study from 1955 to 1968.

Stability of initial fixation of the tibial component in cementless total knee arthroplasty.

This study measured the vertical displacement of three kinds of cementless tibial components [Porous Coated Anatomical (PCA), Tricon, and Whiteside], under eccentric loading up to 2,225 N. Displacement between the tibial tray and the proximal tibia was measured with linear variable differential transformers at the anterior and posterior side when anteriorly or posteriorly loaded, and at the medial and lateral side when medially or laterally loaded. The general pattern of motion was sinking at the loaded side and lift-off at the opposite side. Lift-off opposite the loaded side was fairly small for all components at all measurement sites. Among the three components, the Whiteside showed the smallest displacements. The Tricon (when anteriorly or posteriorly loaded), and the PCA (when medially or laterally loaded) showed sinking at the loaded side. Anterior screw fixation of the PCA was not effective in preventing anterior lift-off. The tilting motion of the tibial components observed in this study implies instability of the initial fixation, which could possibly compromise bony ingrowth. Furthermore, this tilting could cause uneven distribution of load, and potentially result in fracture of the underlying bone.

Prosthetic metals impair murine immune response and cytokine release in vivo and in vitro.

This study was designed to investigate whether prosthetic metals adversely affect immune responses and the release of immunoregulatory cytokines in vivo and in vitro. Titanium and cobalt-chromium alloy were injected into the peritoneal cavity of female mice. At 5, 8, and 12 weeks after the injection, the levels of cobalt and chromium in the blood were significantly increased compared with the levels in control mice; the level of titanium was not significantly changed until 12 weeks. The release of interleukin-2 was significantly inhibited by cobalt-chromium particles after 3 weeks; titanium particles did not have the same effect until 8 and 12 weeks. The release of interleukin-4 was significantly inhibited by cobalt-chromium particles after 3 weeks but was not significantly inhibited by titanium particles until 12 weeks. The release of interferon-gamma was significantly inhibited by cobalt-chromium particles only at 12 weeks and was not inhibited by titanium particles. The proliferation of T cells was significantly inhibited by cobalt-chromium particles at 3 weeks and by titanium particles at 8 and 12 weeks, and the proliferation of B cells was significantly inhibited by cobalt-chromium particles after 3 weeks but was not inhibited by titanium particles. The production of immunoglobulin by lipopolysaccharide-stimulated B cells was also significantly reduced by cobalt-chromium particles after 3 weeks and by titanium particles at 8 and 12 weeks. The cytokine release by lymphocytes, proliferation of T and B cells, and immunoglobulin production by B cells were also significantly inhibited by titanium and cobalt-chromium particles, as well as by titanium, cobalt, and chromium ions in vitro, whereas these metals are not cytotoxic to murine lymphocytes in vitro. The data indicate that the metal-induced immunosuppression may be another important factor in the development of implant-associated infection in patients with a prosthesis.

Joint replacement in non-ambulatory patients.

We treated eighteen non-ambulatory patients by multiple operations consisting of total replacement of the hip or the knee, or both. Thirteen patients had rheumatoid arthritis, four had degenerative arthritis, and one had had bilateral resection of the femoral head and neck. The patients were followed for an average of forty months. We devised a classification based on the number of joints involved and a rating scale for function. Good to excellent results were achieved in the patients who had two or three joints operated on (with one exception). Fifteen patients became ambulatory and seven could climb stairs. Seven patients were pain-free. The factors responsible for poor results were significant neural problems and loss of motivation. The presence of severe upper-extremity involvement was not an obstacle preventing walking.

Prevention of infection in the treatment of one thousand and twenty-five open fractures of long bones: retrospective and prospective analyses.

In 673 open fractures of long bones (tibia and fibula, femur, radius and ulna, and humerus) treated from 1955 to 1968 at Hennepin County Medical Center, Minneapolis, Minnesota, and analyzed retrospectively, the infection rate was 12 per cent from 1955 to 1960 and 5 per cent from 1961 to 1968. In a prospective study from 1969 to 1973, 352 patients were managed as follows: débridement and copious irrigation, primary closure for Type I and II fractures and secondary closure for Type III fractures, no primary internal fixation except in the presence of associated vascular injuries, cultures of all wounds, and oxacillin-ampicillin before surgery and for three days postoperatively. In 158 of the patients in the prospective study the initial wound cultures revealed bacterial growth in 70.3 per cent and the infection rate was 2.5 per cent. Sensitivity studies suggested that cephalosporin is currently the prophylactic antibiotic of choice. For the Type III open fractures (severe soft-tissue injury, segmental fracture, or traumatic amputation), the infection rates were 44 per cent in the retrospective study and 9 per cent in the prospective study.

Refracture of bones of the forearm after plate removal.

Thirty-two plates originally used for fracture fixation in the ulna and radius in twenty-three patients were removed at Hennepin County Medical Center in Minneapolis between 1977 and 1982. The plate was on the ulna in eighteen arms and on the radius in fourteen. Removal of twenty-one plates was elective, and eleven were removed because of slight pain or discomfort. The interval between plate application and plate removal ranged from eight to sixty-two months. The average duration of cast immobilization used for protection after removal of the plate was six weeks. There were seven refractures, which occurred between two and forty weeks after plate removal. Three refractures occurred at the former fracture site; three, through the fracture site, extending into an adjacent screw-hole; and one, at one screw-hole. No refracture occurred more than forty weeks after removal of the plate.

Infection after total hip arthroplasty. A study of the treatment of one hundred and six infections.

We evaluated the results of treatment for ninety-seven patients (106 infections in ninety-eight hips) who had had either an infection after a total hip arthroplasty or positive intraoperative cultures of specimens obtained during revision of a total hip arthroplasty for presumed aseptic loosening. The patients were managed according to various protocols on the basis of the clinical setting (positive intraoperative cultures, early postoperative infection, late chronic infection, or acute hematogenous infection). Aerobic gram-positive cocci accounted for 109 (74 per cent) of the 147 microbial isolates; gram-negative bacilli, for twenty-one (14 per cent); and anaerobes, for twelve (8 per cent). The white blood-cell count and erythrocyte sedimentation rate were elevated in association with seventeen (16 per cent) and sixty-seven (63 per cent) of the 106 infections, respectively. The mean duration of follow-up was 3.8 years (range, 0.3 to eleven years). A good result was noted after the initial treatment of twenty-eight (90 per cent) of the thirty-one infections that had been diagnosed on the basis of positive intraoperative cultures at the time of the revision, twenty-five (71 per cent) of the thirty-five early postoperative infections, twenty-nine (85 per cent) of the thirty-four late chronic infections, and three of the six acute hematogenous infections. Of the twenty++-one infections for which the initial therapy failed, twelve eventually were eradicated after additional treatment and the hip had a functional prosthesis at the time of follow-up. Of the ninety-seven infections that were treated successfully (there was a functional retained or exchange prosthesis in place at the time of the most recent follow-up and infection had not recurred at least two years after the discontinuation of antibiotic therapy), nine were associated with subsequent aseptic loosening of the prosthesis. The factors associated with recurrent infection were retained bone cement, the number of previous operations, potential immunocompromise, and early postoperative infection after arthroplasty without cement.

The timing of flap coverage, bone-grafting, and intramedullary nailing in patients who have a fracture of the tibial shaft with extensive soft-tissue injury.

The cases of forty-three patients who had a Type-IIIB open fracture of the tibial shaft were reviewed to determine the effect of treatment of the soft-tissue injury on the rate of major complications. An infection developed in two of the eleven patients who had had early muscle-flap coverage compared with ten of the nineteen who had been managed by open care of the wound and nine of the thirteen who had had later flap coverage. Patients who had had bone-grafting after complete re-epithelialization of the wound, regardless of the method of closure, had a lower rate of early infection (none of sixteen compared with four of fifteen) and an earlier average time to union (fifty-four compared with sixty-three weeks) than those in whom the wound was not completely closed or was draining at the time of bone-grafting. Delayed intramedullary nailing with reaming was associated with a high rate of infection (nine of nineteen patients), regardless of the condition of the soft tissue at the time of nailing. In our opinion, adequate débridement and early assessment of the soft-tissue defect are necessary so that appropriate soft-tissue coverage can be provided within the first one to two weeks. When the soft-tissue portion of the injury is addressed promptly and definitively and then allowed to heal completely, secondary osseous reconstruction may proceed with fewer complications.

Results of operative treatment of displaced external rotation-abduction fractures of the ankle.

One hundred and fifty patients with a displaced fracture of the ankle caused by external rotation-abduction forces were treated by open reduction and rigid internal fixation. After an average follow-up of three and one-half years, the results were satisfactory in 90 per cent. Less satisfactory results were noted in the more severely injured ankles. We found that the ruptured deltoid ligament did not need to be repaired if the lateral side was anatomically and rigidly fixed; in the Maisonneuve fracture, restoration of the fibular length was as important as stabilization of the fracture; with the use of the suprasyndesmotic screw, walking was permissible with the screw in situ; conforming the plate to the bend of the lateral malleolus was essential; and as much as two millimeters of lateral residual displacement of the lateral and medial malleoli was compatible with a satisfactory result, as was a similar displacement of the talus provided there was anatomical restoration of the lateral side.

Analysis of six hundred and twenty-two intertrochanteric hip fractures.

Of 622 intertrochanteric fractures, 57% were stable (Types I and II). Twenty-eight per cent were Type III, and 15% were Type IV (the unstable types). The 150-degree telescoping Massie nail proved superior to the fixed 135-degree Jewett nail (particularly for unstable fractures) because it allowed a controlled impaction of the fracture fragments to a stable position. In about one-third of the fractures, some medial displacement occurred. With anatomical reduction and the use of the Massie or ASIF nails, we achieved a decrease in the morbidity and mortality and 96% satisfactory results. Our prospective study was compared with a retrospective study in which other devices were used. Early ambulation and weight-bearing also was a major contributing factor to the improved results in the prospective study. Intertrochanteric hip fractures that are unstable can be fixed with a collapsible nail, and that treatment appears to give as good or better results than the displacement method of Dimon and Hughston or Sarmiento.

Infection after intramedullary nailing of severe open tibial fractures initially treated with external fixation.

Twenty-four patients had a severe open fracture of the tibia that was initially treated by external fixation and subsequently by reamed intramedullary nailing. The external fixation had been maintained for an average of fifty-two days (range, seven to 230 days). The mean interval between removal of the external fixator and intramedullary nailing was sixty-five days (range, three to 360 days). In five of the seven patients who had had an infection at one or more of the pin sites, an infection later developed around the intramedullary nail. In comparison, only one of the seventeen patients who had not had a pin-site infection had an infection later around the nail (p = 0.003). An analysis of other variables, including the duration of external fixation, wound coverage, other injuries, and the type of fracture, showed that none was a predictor of infection either at the pin sites or around the intramedullary nail. We concluded that a pin-site infection that develops during external fixation is a contraindication to the subsequent use of reamed intramedullary nailing in patients who have a fracture of the tibia.

Prophylactic antibiotics in hip fractures. A double-blind, prospective study.

Three hundred and seven patients, each of whom had a fracture of the proximal part of the femur, were studied in a randomized, double-blind fashion to determine whether perioperative administration of cephalothin would prevent postoperative infection. Major postoperative wound infections were significantly reduced in the cephalothin-treated group (4.7 per cent versus 0.7 per cent; p less than 0.05). There also was a reduction in the incidence of postoperative urinary-tract infections and a reduction in mean peak body temperatures. The duration of hospitalization was not affected and no hospital stay was prolonged by complications of antibiotic administration. However, in the cephalothin-treated group, a strong trend toward colonization by cephalothin-resistant organisms was noted.

Infection after total knee arthroplasty. A retrospective study of the treatment of eighty-one infections.

BACKGROUND: The clinical presentation of an infection at the site of a total knee arthroplasty can be used as a guide to treatment, including the decision as to whether the prosthesis should be retained or removed. We reviewed the results of treatment of infection after total knee arthroplasty to evaluate the effectiveness of four treatment protocols based on the clinical setting of the infection. METHODS: We retrospectively evaluated the results of treatment of eighty-one infections in seventy-six consecutive patients who either had an infection after a total knee arthroplasty or had multiple positive intraoperative cultures of specimens of periprosthetic tissue obtained during a revision total knee arthroplasty performed because of presumed aseptic loosening. The patients were managed according to one of four protocols. Five infections in five patients who had positive intraoperative cultures were treated with antibiotic therapy alone. Twenty-three early postoperative infections in twenty-one patients were treated with débridement, antibiotic therapy, and retention of the prosthesis. Twenty-nine late chronic infections in twenty-eight patients were treated with a delayed-exchange arthroplasty after a course of antibiotics. Seven acute hematogenous infections in six patients were treated with débridement, antibiotic therapy, and retention of the prosthesis. Seventeen infections in seventeen patients were not treated according to one of the four protocols. Sixteen late chronic infections were treated either with an arthrodesis (five infections) or with débridement, antibiotic therapy, and retention of the prosthesis (eleven infections). One acute hematogenous infection was treated with resection arthroplasty because of life-threatening sepsis. RESULTS: The mean duration of follow-up was 4.0 years (range, 0.3 to 14.0 years). Eleven patients who had an arthrodesis, a resection arthroplasty, or an above-the-knee amputation after less than two years of follow-up were included in the study as individuals who had a failure of treatment. In the group of patients who were managed according to protocol, the initial course of treatment was successful for all five infections that were diagnosed on the basis of positive intraoperative cultures, five of the ten deep early infections, all thirteen superficial early infections, twenty-four of the twenty-nine late chronic infections, and five of the seven acute hematogenous infections. Only one of eleven prostheses in patients who had a late chronic infection that was not treated according to protocol was successfully retained after débridement. CONCLUSIONS: Our treatment protocols, which were based on the clinical setting of the infection, were successful for most patients. A major factor associated with treatment failure was a compromised immune status. Bone loss and necrosis of the soft tissues around the joint also complicated the treatment of these infections.

Radiographic changes in bone dimensions in asymptomatic cemented total hip arthroplasties. Results of nine to thirteen-year follow-up.

On twenty-six cemented total hip replacements that had been followed for an average of 10.4 years (range, nine to thirteen years), a retrospective radiographic study was done to assess dimensional changes in the cross section of the bone in a group of asymptomatic patients. Cortical dimensions were measured on radiographs and were normalized using a radiographic distortion factor that was derived from the width and length of the prosthesis. The data were then analyzed using a least-squares method. Analyses were performed for the men, for the women, and for the combined group. The results for all three groups showed a significant decrease in cortical thickness as well as widening of the medullary canal, but no periosteal expansion.

Immediate internal fixation in open fractures.

Open fractures require emergency treatment. Adequate debridement and copious irrigation are essential in their management. The parenteral administration of antibiotics should be started immediately. If the wound is closed primarily, the antibiotics are discontinued after three days. If the wound is closed secondarily, the antibiotics are continued for another three days after this procedure. Most open fractures should be treated without the use of internal fixation techniques. However, we believe that there are reasons for employing immediate internal fixation, particularly in polytraumatized patients and others sustaining type III open fractures, to facilitate care of the soft tissue. When immediate internal fixation techniques are used in open fractures, the wound must not be closed primarily.

Revision of femoral component loosening with titanium ingrowth prosthesis and bone grafting.

Preliminary results of 24 cementless revision hips are very encouraging and show no evidence of loosening at 12 to 45 months follow-up. With the problem inherent in femoral component loosening and the high incidence of failure from cemented revision total hip arthroplasty, the use of a porous ingrowth long stem prosthesis fitted to the canal with bone grafting proximally offers a logical solution to a very difficult problem.

The use of antibiotics in the management of open fractures.

Successful management of Type III open fractures requires adherence to the following principles: 1) treatment of all open fractures as emergencies; 2) thorough initial evaluation to diagnose other life-threatening injuries; 3) appropriate antibiotic therapy for both grampositive and gram-negative bacteria; 4) adequate debridement and irrigation, with repeat debridement and irrigation in 12 to 48 hours; 5) stabilization of the fractures; 6) appropriate wound coverage; and 7) early cancellous bone grafting. Recent experience has warranted categorizing Type III fractures into subtypes A, B and C, in order of worsening prognosis. The increasing prevalence of infection due to gram-negative organisms is treated by combined use of an aminoglycoside with cefazolin, or ceforanide with amikacin, or a third generation cephalosporin in Type III fractures.

Suppressive antibiotic therapy in chronic prosthetic joint infections.

Thirteen patients with chronic total joint infections (eight knees, five hips) were treated with suppressive antibiotic therapy and retention of the prosthesis following surgical debridement and 4 to 6 weeks of intravenous antibiotic therapy. These patients faced poor functional outcome after prosthesis removal. After a mean follow up of 37.6 months (range: 24 to 55), only three patients have retained their prostheses. Ten patients required prosthesis removal for recurrent infection a mean of 21.6 months (range: 6 to 48) after starting suppressive therapy. In addition, 38% of patients experienced adverse effects which led to changes in the antibiotic regimen. Suppressive antibiotic therapy in the treatment of chronic prosthesis infections has limited clinical efficacy and is associated with a substantial risk of adverse effects.