Tranexamic acid toxicity in human periarticular tissues.

OBJECTIVES: Tranexamic acid (TXA) is an anti-fibrinolytic medication commonly used to reduce perioperative bleeding. Increasingly, topical administration as an intra-articular injection or perioperative wash is being administered during surgery. Adult soft tissues have a poor regenerative capacity and therefore damage to these tissues can be harmful to the patient. This study investigated the effects of TXA on human periarticular tissues and primary cell cultures using clinically relevant concentrations. METHODS: Tendon, synovium, and cartilage obtained from routine orthopaedic surgeries were used for ex vivo and in vitro studies using various concentrations of TXA. The in vitro effect of TXA on primary cultured tenocytes, fibroblast-like synoviocytes, and chondrocytes was investigated using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) cell viability assays, fluorescent microscopy, and multi-protein apoptotic arrays for cell death. RESULTS: There was a significant (p < 0.01) increase in cell death within all tissue explants treated with 100 mg/ml TXA. MTT assays revealed a significant (p < 0.05) decrease in cell viability in all tissues following treatment with 50 mg/ml or 100 mg/ml of TXA within four hours. There was a significant (p < 0.05) increase in cell apoptosis after one hour of exposure to TXA (100 mg/ml) in all tissues. CONCLUSION: The current study demonstrates that TXA caused significant periarticular tissue toxicity ex vivo and in vitro at commonly used clinical concentrations.Cite this article: M. McLean, K. McCall, I. D. M. Smith, M. Blyth, S. M. Kitson, L. A. N. Crowe, W. J. Leach, B. P. Rooney, S. J. Spencer, M. Mullen, J. L. Campton, I. B. McInnes, M. Akbar, N. L. Millar. Tranexamic acid toxicity in human periarticular tissues. Bone Joint Res 2019;8:11-18. DOI: 10.1302/2046-3758.81.BJR-2018-0181.R1.

Effect of body mass index and osteoarthritis on outcomes following arthroscopic meniscectomy: a prospective nationwide study.

BACKGROUND: Current evidence suggests limiting arthroscopic meniscectomy to those patients with no or early arthritis however outcomes of arthroscopic meniscectomy with patients of a higher body mass index (BMI) are not as widely available. The aim of this study was to determine if patient reported outcome scores for arthroscopic meniscectomy are adversely affected by the degree of knee osteoarthritis or patient BMI. METHODS: All patients who underwent arthroscopic meniscectomy within the NHS in Scotland between the 6th of February and 29th of April 2012 were audited as part of the Scottish Government Musculoskeletal Audit and were eligible for inclusion within this study. A total of 270 patients returned both their pre-operative and post-operative EuroQol 5Q5D5L descriptive questionnaire and Knee injury and Osteoarthritis Outcomes Scores. Patients were stratified according to BMI, degree of osteoarthritis, history of injury, and duration of knee symptoms. RESULTS: Pre-operative to post-operative EuroQol index scores [0.642±0.253 to 0.735±0.277, median±SD] and Knee injury and Osteoarthrtis Outcome Scores [44.63±18.78 to 62.28±24.94, median±SD] improved across all patients (p<0.0001). This was irrespective of degree of BMI, history of injury, or duration of symptoms. There was no such improvement in patients with moderate to severe osteoarthritis. Those patients with a BMI >35 kg/m2 had lower post-operative scores than the pre-operative scores of those of BMI <30 kg/m2. CONCLUSIONS: Arthroscopic meniscectomy is beneficial regardless of patient BMI, duration of symptoms, history of injury, or in the presence of early osteoarthritis.

No clinical difference between fixed- and mobile-bearing cruciate-retaining total knee arthroplasty: a prospective randomized study.

PURPOSE: It is hypothesized that mobile polyethylene bearings in total knee arthroplasty (TKA) may confer benefits with regard to range of motion and have improved clinical outcome scores in comparison with an arthroplasty with a fixed-bearing design. Our study compares clinical outcomes between patients who undergo TKA with either a rotating platform or fixed bearing using a posterior cruciate-retaining design. METHODS: Three hundred and thirty-one patients were randomized to receive either a rotating-platform (161 patients) or a fixed-bearing (170 patients) implant. All patients were assessed pre-operatively and at 1 and 2 years post-operatively using standard tools (range of movement, Oxford Knee Score, American Knee Society Score, SF12 and Patella Score). RESULTS: There was no difference in pre- to 2-year post-operative outcomes between the groups with regard to improvement in range of motion (10° ± 16 vs. 9° ± 15), improvement in Oxford Knee Score (-17.6 ± 9.9 vs. -19.1 ± 8.4), improvement in American Knee Society Score (49.5 ± 24.7 vs. 50.7 ± 21.0), function (23.6 ± 19.6 vs. 25.0 ± 22.5) and pain (34.9 ± 16.2 vs. 35.8 ± 14.1) subscores, improvement in SF12 Score (10.0 ± 16.3 vs. 12.3 ± 15.8) or improvement in Patella Score (9.7 ± 7.4 vs. 10.6 ± 7.1). CONCLUSION: No difference was demonstrated in clinical outcome between patients with a rotating-platform and fixed-bearing posterior cruciate-retaining TKA at 2-year follow-up. LEVEL OF EVIDENCE: I.

Rates of infection and revision in patients with renal disease undergoing total knee replacement in Scotland.

We undertook a study to determine the rates of infection and revision of total knee replacement (TKR) in patients with renal failure, renal transplantation and those undergoing renal dialysis in Scotland. The overall early and late infection rates were 1.10% and 2.19% compared with 1.06% and 2.01%, respectively, for non-renal patients. Patients with renal failure had a significantly increased risk of early infection (1.6%, relative risk 1.52, p = 0.002) and late infection (4.47%, relative risk 2.22, p < 0.001). Those on renal dialysis had significantly increased risks of late infection (8.03%, relative risk 3.99, p < 0.001) and early revision (3.70%, relative risk 4.40, p < 0.001). Renal transplant patients had a significantly increased risk of late infection, regardless of whether renal transplantation occurred before TKR (9.09%, relative risk 4.517, p = 0.027) or at any time (8.0%, relative risk 3.975, p = 0.047). There were significantly increased rates of comorbidities associated with infection for all the renal patient groups. Logistic regression analysis showed that renal failure and renal dialysis were independent risk factors for early infection and revision, respectively.

Locked intramedullary nailing of symptomatic metastases in the humerus.

The humerus is a common site for skeletal metastases in the adult. Surgical stabilisation of such lesions is often necessary to relieve pain and restore function. These procedures are essentially palliative and should therefore provide effective relief from pain for the remainder of the patient's life without the need for further surgical intervention. We report a retrospective analysis of 35 patients (37 nails) with symptomatic metastases in the shaft of the humerus which were treated by locked, antegrade nailing. There were 27 true fractures (73.0%) and ten painful deposits (27.0%). Relief from pain was excellent in four (11.4%), good in 29 (82.9%) and fair in two (5.7%) on discharge. Function was improved in all but one patient. One case of palsy of the radial nerve was noted. The mean postoperative survival was 7.1 months (0.2 to 45.5) which emphasises the poor prognosis in this group of patients. There were no failures of fixation and no case in which further surgery was required. Antegrade intramedullary nailing is an effective means of stabilising the humerus for the palliative treatment of metastases. It relieves pain and restores function to the upper limb with low attendant morbidity.

Retention of the patella in total knee arthroplasty for rheumatoid arthritis.

AIM: To determine whether retention of the native patella during total knee arthroplasty is appropriate in patients with rheumatoid arthritis. METHODS: All patients undergoing total knee arthroplasty with a diagnosis of rheumatoid arthritis were identified between January 1997 and December 2000. Subsequently, each individual underwent both radiological and clinical assessments at a designated follow-up clinic. RESULTS: A total of 30 total knee arthroplasties were studied in 28 patients. Twenty-six patients (93%) were female with a mean age of 74.7 years (range 60-83 years). The average post-operative interval was 59.4 months (range 46-82 months). All individuals were noted to have satisfactory patellar tracking and bone stock at the time of surgery. No patient subsequently underwent revision surgery during follow-up and no episodes of implant sepsis were identified. The mean Patellar Score at final follow-up was 26.2 (range 22-30) with an average anterior knee pain score of 14.2 (range 10-15). The mean Oxford Knee Score was 18.7 (range 16-23) with a mean pain score component of 5.9. Patients were finally assessed with respect to the Knee Society Score. The mean Knee Score was 83.8 (range 71-96) with a mean Function Score of 79.7 (range 40-90). CONCLUSION: By retaining the native patella we were still able to obtain highly satisfactory medium-term results in terms of pain relief and function. In addition, the potential complications associated with prosthetic replacement of the patella were avoided.

BTB ACL reconstruction: femoral nerve block has no advantage over intraarticular local anaesthetic infiltration.

Fifty patients were randomly recruited to receive either femoral nerve block (0.375% Bupivacaine) or an intraarticular local anaesthetic injection for pain control for arthroscopically-assisted ACL reconstruction. Both groups were evenly matched for age ( t-test p >0.05). Tourniquet time did not differ significantly between the groups ( t-test p=0.24). The VAS pain levels were not significantly different at 4 h and the first morning postoperatively in both groups. Femoral block (Median VAS: 20 & 18.5) did not confer a significant advantage (Mann Whitney U test p =0.36, 0.67) over intraarticular injection of bupivacaine (Median VAS: 18 & 20). There was no correlation between tourniquet time and postoperative pain ( r=0.19, 0.08). All patients but one were discharged home on the first postoperative morning. Our study demonstrates that pain levels can be sufficiently controlled by intraarticular infiltration of bupivacaine coupled with oral analgesia. The level of pain relief achieved could allow this procedure to be performed in a day surgery setting.

Surgical management of tendinopathy of the main body of the patellar tendon in athletes.

OBJECTIVE: To report the results of surgery for tendinopathy of the main body of the patellar tendon. DESIGN: Retrospective study. SETTING: A teaching hospital of the University of London. PATIENTS: Twenty-eight patients reviewed at an average follow-up of 42 months from surgery for tendinopathy of the main body of the patellar tendon after failed conservative treatment. INTERVENTION: Exploration of the affected patellar tendon, stripping of the paratenon, excision of pathological areas, and multiple longitudinal tenotomies. MAIN OUTCOME MEASURES: Postoperative complications, ability to return to sport, and subjective satisfaction, as measured by formal clinical assessment or telephone questionnaire. RESULTS: At follow-up, 23 patients were completely free of pain and had resumed full sporting activity at the same preoperative level. Three patients were improved enough to have returned to their preoperative sporting level or just below it. In two patients, the initial operation failed. In the patients who resumed sport, the average time from surgery to resuming full sporting activity was 7 months (range 6 weeks to 12 months). The most common early postoperative complications were wound hematoma and superficial infection. The most common late complications were related to the incision, with anterior knee pain on kneeling and skin dysesthesia. CONCLUSION: Surgical decompression of the patellar tendon with multiple longitudinal tenotomies is an effective treatment for patellar tendinopathy. In the middle term, patients do not seem to relapse once they have recovered, whereas those who do not respond to surgery do not recover at all and may need a new operation.

Rotator-cuff tear of the hip.

We describe an apparently unreported finding during hip operations: a tear at the insertion of gluteus medius and gluteus minimus. This defect may well be known to many surgeons with experience of hip replacement and hemiarthroplasty for fractures of the neck of the femur, but a Medline search has failed to find a previous description. We made a prospective study of 50 consecutive patients with fractures of the neck of the femur to quantify the incidence of this condition: 11 (22%) had such a tear.

Synergistic effect of a recombinant N-terminal fragment of bactericidal/permeability-increasing protein and cefamandole in treatment of rabbit gram-negative sepsis.

As a consequence of their bactericidal actions, many antibiotics cause the release of endotoxin, a primary mediator of gram-negative sepsis. Bactericidal/permeability-increasing protein (BPI) has bactericidal activity and neutralizes endotoxin in vitro and in vivo. We sought to examine the effect of a recombinant N-terminal fragment of BPI (rBPI21) in conjunction with cefamandole, a cephalosporin antibiotic, in the treatment of Escherichia coli bacteremia and septic shock in rabbits. Cefamandole (100 mg/kg of body weight) was injected intravenously. This was followed by simultaneous 10-min infusions of E. coli O7:K1 (9 x 10(9) CFU/kg) and rBPI21 (10 mg/kg). rBPI21 was continuously infused for an additional 110 min at 10 mg/kg/h. The administration of rBPI21 in conjunction with the administration of cefamandole prevented the cefamandole-induced increase of free endotoxin in plasma, accelerated bacterial clearance, ameliorated cardiopulmonary dysfunction, and thereby, prevented death, whereas neither agent alone was protective in this animal model. The efficacy of the combined treatment with rBPI21 and cefamandole suggests a synergistic interaction between the two agents. The data indicate that rBPI21 may be useful in conjunction with traditional antibiotic therapy.

Protective effects of a recombinant N-terminal fragment of bactericidal/permeability increasing protein on endotoxic shock in conscious rabbits.

Endotoxin (lipopolysaccharide, LPS) can induce shock, multiple organ failure, and death. A recombinant N-terminal fragment of bactericidal/permeability increasing protein, rBPI23, binds with high affinity to gram-negative bacterial LPS and neutralizes its biological activity. We sought to determine the effect of rBPI23 on LPS-induced respiratory dysfunction and cardiovascular depression in conscious rabbits. Rabbits were injected with Escherichia coli O113 LPS (6 micrograms/kg) and treated with rBPI23 (2 mg/kg), vehicle, or control protein after recovery from surgery performed to implant catheters for hemodynamic assessments and intravenous injections. LPS challenge caused respiratory dysfunction including tachypnea, significant decreases in arterial O2 tension (PO2), arterial oxygen content, and an increase in alveolar-arterial O2 gradient (A-aDO2). LPS administration also resulted in profound and prolonged decreases in mean arterial blood pressure and cardiac index. Treatment with rBPI23 prevented LPS-induced respiratory dysfunction and significantly ameliorated the cardiovascular depression. 5 of 16 LPS-challenged animals died of respiratory failure and acidosis, whereas none died in the rBPI23 treated group (p = .11). The results demonstrate that rBPI23 protects animals against LPS-induced cardiopulmonary depression in endotoxic shock.

Audit of ankle fracture fixation in the elderly.

To assess the results of operative treatment of ankle fractures in the elderly, we have reviewed the results of ankle fracture fixation in 76 patients aged over 50 years. This was carried out with special reference to the early complications. Our series had a 1.8% incidence of infection and a 5.2% incidence of delayed healing and wound necrosis. Malunion occurred in 7.9% of patients, and was due in all cases to either imperfect peroperative reduction or inadequate fixation. In no case did fixation fail because of poor bone quality. We conclude that internal fixation of ankle fractures in the elderly carries acceptable risks, so long as careful attention is paid to surgical technique, and fixation is in accordance with AO/ASIF principles.

Grip strength following carpal tunnel decompression.

To monitor the effect of open carpal tunnel decompression on grip strength in the hand, a prospective study was made of 25 patients undergoing a total of 31 operations. Hand grip, key pinch and pulp-to-pulp pinch strengths were measured pre-operatively and at regular intervals until 1 year following operation. At that time there was no significant difference in the hand grip and pulp-to-pulp pinch strengths compared to their pre-operative values, but the key pinch in females showed a marginally significant reduction (P = 0.04) compared to the pre-operative value.

Trends in infection prophylaxis in orthopaedics.

The current measures employed by consultant orthopaedic surgeons in Scotland to prevent infection were established by postal questionnaire. Our findings were compared with those of a similar study carried out 5 years previously. An increasing number of surgeons use routine systemic antibiotic prophylaxis for total hip arthroplasty (99% versus 91% 5 years ago), in treating compound fractures (89% versus 75% 5 years ago) and for internal fixation of closed fractures with metal implants (49% versus 12% 5 years ago). Cephalosporins are increasingly used as the antibiotic of choice. By starting antibiotics earlier than the day of surgery or continuing for more than 24 h after surgery, just over half the surgeons questioned administer antibiotics for longer than would seem to be necessary for elective surgery.

Management of tibial fractures with the orthofix dynamic external fixator.

We report our experience with the use of the Orthofix external fixator for the management of closed and open tibial fractures. One hundred fractures were treated in 96 patients between May 1985 and December 1989. There were 47 closed and 53 open fractures. Of the open fractures, 11 were grade I, 16 were grade II and 26 were grade III. Forty-five closed fractures and 49 open fractures went on to solid bony union in an average of 15.2 and 20.5 weeks, respectively. Non-union requiring operative intervention occurred in two closed and four open fractures (6%). The other main complications were pin track infection (30% of cases) and malunion which occurred in 14% of closed fractures and 32% of open fractures. We concluded that dynamic axial fixation is a useful method of treatment for open and difficult closed tibial fractures. Our experience indicates that malunion and pin track infection remain common problems and have still to be overcome.

Saddle embolus as first presentation of left atrial myxoma in a 14-year-old girl.

A 14-year-old girl was brought to the A & E department minutes after collapsing while out walking minutes earlier. She had developed sudden, severe, cramping pain in her lower abdomen and both legs, and had been incontinent of urine. Earlier that day she had an episode of diarrhoea. The girl was previously in excellent health.

Synergistic protection from lung damage by combining antithrombin-III and alpha 1-proteinase inhibitor in the E. coli endotoxemic sheep pulmonary dysfunction model.

Septicemic/endotoxic-induced adult respiratory distress syndrome (ARDS) remains a major clinical problem. The present study was to determine in the E. coli endotoxemic sheep ARDS model the efficacy of combination prophylaxis with antithrombin-III (AT-III) and alpha 1-proteinase inhibitor (alpha 1-PI). We reasoned that 1) AT-III supplementation would ameliorate the endotoxin-induced coagulopathy, 2) alpha 1-PI supplementation would attenuate pulmonary damage caused by neutrophil elastase and inactivation of AT-III by neutrophil elastase, and 3) the therapeutic effects of this combination would be additive or synergistic. The typical increases in lung lymph flow microvascular permeability to protein, transvascular protein flow and transvascular protein clearance, and decrease in systemic arterial PO2 were prevented or significantly attenuated during 5 hours of endotoxemia by the AT-III/alpha 1-PI combination pretreatment. Limited efficacy was observed with AT-III pretreatment, and none was seen with alpha 1-PI alone. Results of this study demonstrate that combining AT-III and alpha 1-PI prophylaxis prevents or attenuates indices of ARDS during gram-negative endotoxemia and that this efficacy is due to a statistically significant synergism between AT-III and alpha 1-PI.

Protection against disseminated intravascular coagulation and death by antithrombin-III in the Escherichia coli endotoxemic rat.

Gram-negative septic shock remains a major clinical problem. One frequently encountered complication of sepsis is disseminated intravascular coagulation (DIC). The present study was to determine in an Escherichia coli endotoxemia awake rat model the efficacy of antithrombin-III (AT-III) prophylaxis and to explore the role of DIC in the pathogenesis of endotoxemia. We demonstrated that DIC occurs very early, before the appearance of detectable serious abnormalities in cardiovascular, metabolic, and biochemical variables indicative of organ damage or dysfunction; AT-III prophylaxis significantly ameliorates DIC, as evidenced by completely preventing the fall in plasma fibrinogen concentration and significantly limiting the increases in prothrombin time and activated partial thromboplastin time after 4 hours of endotoxemia; and AT-III prophylaxis dramatically increases permanent survival. Results of this study suggest that AT-III prophylaxis is very protective above a threshold dosage in an endotoxemic rat model and that protection is in part due to ameliorating DIC. Our data also suggest that DIC occurs very early during endotoxemia and may in part be responsible for the pathogenesis of endotoxemia in the rat. We conclude that AT-III prophylaxis may be efficacious in conditions of impending DIC, such as gram-negative septicemia/endotoxemia.