Complete mid-portion rupture of the rat achilles tendon leads to remote and time-mismatched changes in uninjured regions.

PURPOSE: To examine healing adaptations over 17 weeks post Achilles tendon (AT) rupture in the injured region (IR) compared to an uninjured region (UIR) of the AT. METHODS: Twenty-four rats were subjected to a complete right-sided AT rupture, while the left side served as a control. ATs were harvested at 1, 2, 8 and 17 weeks post-rupture and stained with antibodies specific to Collagen type I (Col I) and II (Col II) as well as Alcian Blue and Picrosirius Red staining techniques. Histopathological changes, proteoglycan content, collagen alignment and immunoexpression were assessed. RESULTS: Both regions examined, IR and UIR, exhibited over weeks 1-17 similar healing adaptations of increasing collagen alignment, decreasing Col I immunoexpression, as well as increasing proteoglycan content and Col II occurrence. Increased proteoglycan content was found already at week 2 in the UIR, while it first increased at week 8 in the IR. The area positive to Col II was increased compared to controls at week 8 in the UIR, whereas it first raised at week 17 in the IR. Collagen disorganization successively declined to reach control levels at week 17 in the UIR, but was still higher in the IR. CONCLUSION: This study demonstrated that uninjured areas of the AT remote from the rupture site also undergo pronounced remodeling, although with time-span differences relative to injured AT portions. These changes including the pathologic heterotopic mineralization and chondrogenic differentiation observed in both regions may have implications in the choice of rehabilitation regimes in order to prevent secondary rupture.

Postoperative Thromboprophylaxis With New Oral Anticoagulants is Superior to LMWH in Hip Arthroplasty Surgery: Findings from the Swedish Registry.

BACKGROUND: Although the use of thromboprophylaxis is well established, there is no consensus on the preferred thromboprophylaxis regimen after THA; large, population-based studies offer an opportunity to examine this problem in a robust way that can complement results from randomized trials. QUESTIONS/PURPOSES: Using data from a large national registry, we asked: (1) Is there any difference between low-molecular weight heparin (LMWH) and new oral anticoagulants in preventing symptomatic deep vein thrombosis (DVT) and pulmonary embolism (PE), after THA? (2) Are there any differences in safety parameters, such as bleeding, reoperations and mortality, between LMWH and new oral anticoagulants? METHODS: Between 2008 and 2012, 78,066 THAs were performed in Sweden. This study evaluated 32,663 (42%) of them, selected through the merger of several national registries. These patients underwent unilateral THA due to primary osteoarthritis. They had not experienced any venous thromboembolic events 5 years before the index operation and were not prescribed potent antithrombotic agents, of any type, in the 6 months before the index operation. Additionally, their postoperative thromboprophylaxis was confirmed in a national registry by purchase of prescribed medications. We divided the cohort into two groups: those patients who received new oral anticoagulants (5752, 18%) and those who received LMWH (26,881, 82%) as postoperative thromboprophylaxis. Our primary endpoints were the frequencies of symptomatic DVT and symptomatic PE within 3 months of surgery. Our secondary comparison was a between-group comparison of bleeding (by way of diagnostic coding), reoperation, and mortality within 3 months of surgery. Odds ratios (OR) are presented with 95% confidence intervals (CIs) as pooled results for the two groups after adjustment for duration of thromboprophylaxis (short or extended for at least 28 days), year of the index operation, Elixhauser comorbidity index, sex, age and previous treatment with platelet aggregation inhibitors. RESULTS: The risk of symptomatic DVT was lower in the group that received new oral anticoagulants than the group that received LMWH (0.3% versus 0.6%, OR, 0.47; 95% CI, 0.27-0.76; p = 0.026). The risk of symptomatic PE was lower in the group that received new oral anticoagulants than the group that received LMWH (0.1% versus 0.4%, OR, 0.36; 95% CI, 0.16-0.69; p = 0.005). There was no difference in the risk of bleeding (by way of diagnostic coding) (OR, 1.03; 95% CI, 0.82-1.28; p = 0.688), reoperation (OR, 1.02; 95% CI, 0.71-1.44; p = 0.860) or mortality (OR, 0.83; 95% CI, 0.31-1.88; p = 0.883) between groups. CONCLUSIONS: New oral anticoagulants were associated with a lower risk of symptomatic DVT and symptomatic PE in this large, registry study, and we observed no differences in the risk of bleeding, reoperation, or death between the groups. Although we were able to control for a number of potential confounding variables, we cannot ascertain the indications that drove the prescription decisions in this setting, and there were important between-group differences in terms of duration of thromboprophylaxis (new oral anticoagulants generally were used for a longer period of time after surgery). Future studies, preferably large randomized trials with pragmatic inclusion criteria, to analyze symptomatic DVT, symptomatic PE and death are needed to confirm or refute our findings. LEVEL OF EVIDENCE: Level III, therapeutic study.

An open-label study of the pharmacokinetics and pharmacodynamics of dabigatran etexilate 150mg once daily in Caucasian patients with moderate renal impairment undergoing primary unilateral elective total knee or hip replacement surgery.

BACKGROUND: In adults with moderate renal impairment (creatinine clearance [CrCl] 30-50mL/min) undergoing total hip or knee replacement (THR/TKR), the recommended dose of dabigatran etexilate is 150mg once daily (qd). We investigated the steady state pharmacokinetics, pharmacodynamics and safety in these patients. METHODS: Single-arm, open-label phase 4 study (NCT01184989) in Caucasian patients receiving dabigatran etexilate 75mg 1-4h after surgery and 150mg qd on days 2-10 (TKR) or days 2-35 (THR). Plasma total dabigatran concentrations (day 6±1) were determined by high-performance liquid chromatography tandem mass spectrometry and indirectly using the commercially available diluted thrombin time (dTT) assay (Hemoclot® Thrombin Inhibitors). RESULTS: Of 112 patients (mean CrCl 42.5mL/min, age 79.1years, 69.6% female), 100 completed the study. Geometric mean trough and peak dabigatran concentrations were 47.5ng/mL (10th-90th percentile 19.7-120) and 166ng/mL (49.1-364), respectively. There were four major bleeding events and no venous thromboembolic events. Dabigatran concentrations determined from dTT (and falling within the assay range of 50-500ng/mL) underestimated actual values by 7.6% (90% confidence interval 5.3, 9.9), which is within the acceptance limits of ±15%. CONCLUSIONS: These findings in Caucasians with moderate renal impairment undergoing THR or TKR support the use of the 150mg qd dose of dabigatran etexilate. With adequate set-up, calibration and quality control the dTT assay might be appropriate for situations, such as serious bleeding or a need for urgent surgery, where determination of dabigatran levels would be helpful.

Preoperative plasma fibrinogen concentration, factor XIII activity, perioperative bleeding, and transfusions in elective orthopaedic surgery: A prospective observational study.

BACKGROUND: Major orthopaedic surgery involves a calculated risk of bleeding. In other groups of surgical patients, low preoperative plasma fibrinogen concentration and factor XIII (FXIII) activity have been associated with an elevated risk of bleeding. In the present study we investigated the association between preoperative fibrinogen plasma concentration and FXIII activity on bleeding and transfusion requirements in patients undergoing a spinal fusion procedure or hip or knee arthroplasty. METHODS: Two hundred and forty-five adult patients undergoing spine fusion surgery (n=52), total unilateral primary hip arthroplasty (n=114), or total knee arthroplasty (n=79) were included in a prospective observational study. Blood samples were collected <24h before surgery and analysed for fibrinogen concentration and FXIII activity. Intraoperative and postoperative bleeding volume and transfusion requirements were recorded. RESULTS: Spinal fusion surgery patients with a low preoperative fibrinogen concentration (≤2.5g/L) had a greater total perioperative median bleeding volume than patients with fibrinogen>2.5g/L (2430 (400-6560) mL vs. 1390 (400-7420) mL, p=0.029). No significant association between low fibrinogen levels and perioperative bleeding volume was observed for arthroplasty patients. There was no association between low fibrinogen levels and transfusion requirements in any of the groups. Low FXIII activity was not significantly associated with bleeding volume and transfusion requirements in any group. CONCLUSION: Measurement of preoperative fibrinogen plasma concentration can identify spinal fusion patients with an increased risk of excessive perioperative bleeding. Measurement of FXIII activity cannot identify orthopaedic patients with elevated risk of bleeding.

Sex Differences in Outcome After an Acute Achilles Tendon Rupture.

BACKGROUND: Tendon healing differs between the sexes. Comparisons in outcome between the sexes after an Achilles tendon rupture are often not possible because of the small cohort (<20%) of women. PURPOSE: To evaluate whether there are any differences in outcome between the sexes by combining the data from 2 large randomized controlled trials that used identical outcome measures. STUDY DESIGN: Cohort study; Level of evidence, 3. METHODS: Included in the evaluation were patients from 2 consecutive randomized controlled trials comparing surgical and nonsurgical treatment performed at our research laboratory. Patients who had a rerupture were excluded from analysis. A total of 182 patients (152 males, 30 females), with mean ± SD age of 40 ± 11 years, were included; 94 (76 males, 18 females) were treated with surgery and 88 (76 males, 12 females) nonsurgically. Patient-reported outcome was evaluated using the Achilles tendon Total Rupture Score (ATRS), and the functional outcome was measured with a heel-rise test (measurement of muscular endurance and heel-rise height) at 6 and 12 months after injury. RESULTS: Male patients had a greater improvement in heel-rise height at 12 months (P = .004). When each treatment group was analyzed separately, it was found that female patients had significantly (P < .03) more symptoms after surgical treatment (mean ± SD ATRS, 59 ± 24) compared with males at 6 (73 ± 19) and 12 months (74 ± 27 vs 86.5 ± 17). This sex difference was not found in the nonsurgical treatment group. For the entire group, there were no significant differences between treatments on ATRS at 6 and 12 months. The surgical group had significantly better results compared with the nonsurgical group in heel-rise endurance at 6 and 12 months and in heel-rise height recovery at 6 months (P < .03 for both). CONCLUSION: Sex differences were demonstrated, and female patients had a greater degree of deficit in heel-rise height as compared with males, irrespective of treatment. Females had more symptoms after surgery both at 6 and 12 months, but this difference was not found when treated nonsurgically. CLINICAL RELEVANCE: Further research is needed to determine whether women will benefit more from nonsurgical compared with surgical treatment after an Achilles tendon rupture.

Hand Contamination, Cross-Transmission, and Risk-Associated Behaviors: An Observational Study of Team Members in ORs.

Team members in ORs have frequent hand contact with many surfaces and sites during high workload, thus increasing the risk for microorganism cross-transmission. This study aimed at identifying risks for hand contamination and microorganism cross-transmission during invasive procedures in ORs. We carried out observations during 22 daytime sessions and analyzed data using qualitative content analysis. The results revealed that clinicians' hands may be contaminated by self-contamination, via objects, or by touching the patient. Contamination may occur before, during, or directly after performing an invasive procedure requiring the use of aseptic technique, which risks cross-transmitting microorganisms. The results of the study contribute detailed knowledge about risk-associated activities and behaviors in relation to performing invasive procedures in the OR. This knowledge provides clinicians, managers, and educators with specific information that can be used in nursing and medical education and in quality improvement projects aimed at improving hand hygiene routines and enhancing aseptic technique.

Oral dabigatran etexilate versus enoxaparin for venous thromboembolism prevention after total hip arthroplasty: pooled analysis of two phase 3 randomized trials.

BACKGROUND: Two phase 3 trials compared 28-35 days of treatment with oral dabigatran 220 mg or 150 mg (RE-NOVATE) or 220 mg (RE-NOVATE II) once daily with subcutaneous enoxaparin 40 mg once daily for prevention of venous thromboembolism (VTE) after elective total hip arthroplasty. METHODS: This prespecified pooled analysis compared the outcomes for the dabigatran 220 mg dose with enoxaparin, which included 4,374 patients. Total VTE (venographic and symptomatic) plus all-cause mortality (primary efficacy), major VTE (proximal deep vein thrombosis [DVT] or non-fatal pulmonary embolism) plus VTE-related death, and bleeding events were evaluated. Efficacy analysis was based on the modified intention-to-treat (ITT) population and safety analysis was based on all treated patients. The common risk difference (RD) for dabigatran versus enoxaparin was estimated using a fixed effects model. RESULTS: Total VTE and all-cause mortality occurred in 6.8 % (114/1,672) and 7.7 % (129/1,682) (RD:-0.8 %, 95 % confidence interval [CI] -2.6 to 0.9) for dabigatran and enoxaparin, respectively. Major VTE plus VTE-related mortality occurred in 2.7 % (46/1,714) and 4.0 % (69/1,711) (RD: -1.4 %, 95 % CI -2.6 to -0.2) of patients receiving dabigatran 220 mg and enoxaparin, respectively. Major bleeding occurred in 1.7 % (37/2,156) and 1.3 % (27/2,157) (RD: 0.5 %, 95 % CI -0.2 to 1.2), for dabigatran and enoxaparin respectively. CONCLUSIONS: Extended prophylaxis with oral dabigatran 220 mg once daily was as effective as enoxaparin 40 mg once daily in reducing the risk of total VTE and all-cause mortality after total hip arthroplasty, with a similar bleeding profile. The clinically relevant outcome of major VTE and VTE-related death was significantly reduced with dabigatran versus enoxaparin. TRIAL REGISTRATION: NCT00657150 and NCT00168818.

Nucleostemin- and Oct 3/4-positive stem/progenitor cells exhibit disparate anatomical and temporal expression during rat Achilles tendon healing.

BACKGROUND: The recent discovery of residing tendon stem/progenitor cells has triggered a growing interest in stem cells as a useful tool in tendon repair. Our knowledge of their involvement in naturally healing tendons is, however, sparse. The aim of this study was to identify and determine stem/progenitor cells in relation to different healing phases and regions in a rat model of Achilles tendon rupture. METHODS: Surgery was performed to create a mid-tendon rupture on the right Achilles tendon of 24 rats, whereas the left tendon was used as a control. Tendons were harvested at one, two, eight and 17 weeks post-rupture and stained with antibodies specific to stem/progenitor cells (Octamer-binding transcription factor 3/4 (Oct 3/4) and nucleostemin), migrating cells (Dynamin 2 (Dyn 2)) and leukocytes (CD45). A histological examination was performed on sections stained with Alcian blue. RESULTS: At one and two weeks post-rupture, a large number of stem/progenitor cells were discovered throughout the tendon. Most of these cells were nucleostemin positive, whereas only a few Oct 3/4-positive cells were found, mainly situated inside the injury region (I region). At eight and 17 weeks, the increment in stem/progenitor cells had diminished to equal that in the control tendons. At all time points, Oct 3/4-positive cells were also found in the connective tissue surrounding the tendon and at the muscle-tendon junction in both ruptured and control tendons and were often seen at the same location as the migration marker, Dyn 2. CONCLUSIONS: The whole length of the Achilles tendon is infiltrated by stem/progenitor cells at early time points after a mid-tendon rupture. However, different stem/progenitor cell populations exhibit varying anatomical and temporal expressions during Achilles tendon healing, suggesting distinct reparative implications. Oct 3/4 may thus act as a more local, migrating stem/progenitor cell involved in injury-site-specific regenerative effects, as compared to the more general proliferative role of nucleostemin-positive stem/progenitor cells.

Transfusions and blood loss in total hip and knee arthroplasty: a prospective observational study.

BACKGROUND: There is a high prevalence of blood product transfusions in orthopedic surgery. The reported prevalence of red blood cell transfusions in unselected patients undergoing hip or knee replacement varies between 21% and 70%. We determined current blood loss and transfusion prevalence in total hip and knee arthroplasty when tranexamic acid was used as a routine prophylaxis, and further investigated potential predictors for excessive blood loss and transfusion requirement. METHODS/MATERIALS: In total, 193 consecutive patients undergoing unilateral hip (n = 114) or knee arthroplasty (n = 79) were included in a prospective observational study. Estimated perioperative blood loss was calculated and transfusions of allogeneic blood products registered and related to patient characteristics and perioperative variables. RESULTS: Overall transfusion rate was 16% (18% in hip patients and 11% in knee patients, p = 0.19). Median estimated blood loss was significantly higher in hip patients (984 vs 789 mL, p < 0.001). Preoperative hemoglobin concentration was the only independent predictor of red blood cell transfusion in hip patients while low hemoglobin concentration, body mass index, and operation time were independent predictors for red blood cell transfusion in knee patients. CONCLUSIONS: The prevalence of red blood cell transfusion was lower than previously reported in unselected total hip or knee arthroplasty patients. Routine use of tranexamic acid may have contributed. Low preoperative hemoglobin levels, low body mass index, and long operation increase the risk for red blood cell transfusion.

Hand hygiene and aseptic techniques during routine anesthetic care - observations in the operating room.

BACKGROUND: More knowledge is needed about task intensity in relation to hand hygiene in the operating room during anesthetic care in order to choose effective improvement strategies. The aim of this study was to explore the indications and occurrence of hand hygiene opportunities and the adherence to hand hygiene guidelines during routine anesthetic care in the operating room. METHODS: Structured observational data on hand hygiene during anesthetic care during 94 surgical procedures was collected using the World Health Organization's observational tool in a surgical department consisting of 16 operating rooms serving different surgical specialties such as orthopedic, gynecological, urological and general surgery. RESULTS: A total of 2,393 opportunities for hand hygiene was recorded. The number of hand hygiene opportunities when measured during full-length surgeries was mean = 10.9/hour, SD 6.1 with an overall adherence of 8.1%. The corresponding numbers for the induction phase were, mean =77.5/h, SD 27.4 with an associated 3.1% adherence to hand hygiene guidelines. Lowest adherence was observed during the induction phase before an aseptic task (2.2%) and highest during full-length surgeries after body fluid exposure (15.9%). CONCLUSIONS: There is compelling evidence for low adherence to hand hygiene guidelines in the operating room and thus an urgent need for effective improvement strategies. The conclusion of this study is that any such strategy should include education and practical training in terms of how to carry out hand hygiene and aseptic techniques and how to use gloves correctly. Moreover it appears to be essential to optimize the work processes in order to reduce the number of avoidable hand hygiene opportunities thereby enhancing the possibilities for adequate use of HH during anesthetic care.

Comparison between mixed and laminar airflow systems in operating rooms and the influence of human factors: experiences from a Swedish orthopedic center.

BACKGROUND: The importance of laminar airflow systems in operating rooms as protection from surgical site infections has been questioned. The aim of our study was to explore the differences in air contamination rates between displacement ventilation and laminar airflow systems during planned and acute orthopedic implant surgery. A second aim was to compare the influence of the number of people present, the reasons for traffic flow, and the door-opening rates between the 2 systems. METHODS: Active air sampling and observations were made during 63 orthopedic implant operations. RESULTS: The laminar airflow system resulted in a reduction of 89% in colony forming units in comparison with the displacement system (P < .001). The air samples taken in the preparation rooms showed high levels of bacterial growth (≈ 40 CFU/m(3)). CONCLUSIONS: Our study shows that laminar airflow-ventilated operating rooms offer high-quality air during surgery, with very low levels of colony forming units close to the surgical wound. The continuous maintenance of laminar air flow and other technical systems are crucial, because minor failures in complex systems like those in operating rooms can result in a detrimental effect on air quality and jeopardize the safety of patients. The technical ventilation solutions are important, but they do not guarantee clean air, because many other factors, such as the organization of the work and staff behavior, influence air cleanliness.

Surgical Predictors of Early Revision Surgery After Anterior Cruciate Ligament Reconstruction: Results From the Swedish National Knee Ligament Register on 13,102 Patients.

BACKGROUND: An important objective of anterior cruciate ligament (ACL) registries is to detect and report early graft failure and revision surgery after ACL reconstruction. PURPOSE: To investigate surgical variables and identify predictors of revision surgery after ACL reconstruction. STUDY DESIGN: Prospective cohort study; Level of evidence, 2. METHODS: This prospective cohort study was based on data from the Swedish National Knee Ligament Register during the years 2005 through 2011. Eight surgical variables were investigated: graft selection, graft width, single-bundle or double-bundle techniques, femoral graft fixation, tibial graft fixation, injury-to-surgery interval, injuries to menisci, and injuries to cartilage. The primary endpoint was the 2-year incidence of revision surgery. Relative risks (RRs) and 95% confidence intervals (CIs) were calculated and adjusted for confounders by use of multivariate statistics. RESULTS: A total of 13,102 patients were included (5541 women [42%] and 7561 men [58%]; P < .001). Hamstring tendon autografts accounted for 90% (11,764 patients) of all reconstructions, of which 96% were performed with a single-bundle technique (11,339 patients). Patellar tendon autografts accounted for the remaining 10% (1338 patients). At index reconstruction, observed injuries to menisci and cartilage were common (40% and 28%, respectively). The overall 2-year incidence of revision surgery was 1.60% (women, 1.57%; men, 1.63%; P = .854). Patients with metal interference screw fixation of a semitendinosus tendon autograft on the tibia had a significantly reduced risk of early revision surgery (RR = 0.32; 95% CI, 0.12-0.90; P = .031). CONCLUSION: Metal interference screw fixation of a semitendinosus tendon autograft on the tibia was an independent predictor of significantly lower 2-year incidence of revision surgery. Graft selection, graft width, a single-bundle or a double-bundle technique, femoral graft fixation, the injury-to-surgery interval, and meniscus injury were not predictors of early revision surgery.

Ilizarov external fixation or locked intramedullary nailing in diaphyseal tibial fractures: a randomized, prospective study of 58 consecutive patients.

PURPOSE: The aim of this study was to compare the Ilizarov circular fixator (IL) and locked intramedullary nailing (IM). PATIENTS AND METHODS: Patients with isolated tibia shaft fractures were randomly allocated to either the IL (n = 31) or IM (n = 27) method. Conventional radiographs, postoperative pain assessment, self-appraisal scores and complications were evaluated. At the clinical 1-year follow-up, the patients were also evaluated by an independent observer. RESULTS: The minority of patients had open fractures, two and nine patients in the IM and IL groups, respectively. Eight patients in the IM group and four in the IL group sustained major complications (p = 0.107). In the IM group, two patients developed compartment syndrome, one deep infection, one hardware failure, one delayed union, one pseudarthrosis and two had a malunion. In the IL group, two patients developed pseudarthrosis and two had a malunion. Superficial pin-site infections were observed in 16 patients in the IL group. The fractures had healed radiographically at 12 weeks in both groups. At the 1-year follow-up, there were differences in pain (VAS) and satisfaction (VAS) scores in favor of IL treatment (VAS, p = 0.03 and p = 0.02, respectively). There were no differences between the groups with regard to range of motion (ROM) in the knee and ankle joints. The registration of local tenderness and pain revealed that there were 19 patients with anterior knee pain in the IM group and one in the IL group at the 1-year follow-up (p < 0.001). CONCLUSION: The IL is a safe and reliable alternative to IM for the treatment of tibial shaft fractures, with a low complication rate and good clinical outcome. Both treatments were well tolerated, but at the 1-year follow-up the patients in the IM group had more pain and were less satisfied. Finally, there was a high frequency of anterior knee pain in the IM group.

Predictors of Clinical Outcome After Acute Achilles Tendon Ruptures.

BACKGROUND: In patients with an acute Achilles tendon rupture, it has not been possible to determine the superiority of a single specific treatment modality over other treatments with respect to symptoms and function. When several pertinent treatment protocols are available for an injury, it is of interest to understand how other variables, such as age, sex, or physical activity level, affect outcome to better individualize the treatment. PURPOSE: To investigate predictors of both symptomatic and functional outcomes after an acute Achilles tendon rupture. STUDY DESIGN: Cohort study (Prognosis); Level of evidence, 2. METHODS: Ninety-three patients (79 men and 14 women; mean age, 40 years) were evaluated prospectively at 3, 6, and 12 months. The main outcome measures in this study were the Achilles tendon Total Rupture Score (ATRS) for symptoms and maximum heel-rise height for function. The independent variables evaluated as possible predictors of outcome included treatment, sex, age, body mass index (BMI), physical activity level, symptoms, and quality of life. RESULTS: Treatment, age, BMI, physical activity level, heel-rise height at 6 months, and the ATRS at 3 months were eligible for further analysis. Only male sex was included for the prediction models. The 4 different multiple linear regression models (predicting the ATRS at 6 and 12 months and heel-rise height at 6 and 12 months) were significant (P < .001-.002), and the R (2) values for the models were 0.222 to 0.409. Surgical or nonsurgical treatment is a moderate predictor of symptoms and a weak predictor of heel-rise height after an acute Achilles tendon rupture. At the 6-month follow-up, surgical treatment was associated with a larger heel-rise height, but the opposite was seen at 12 months. Surgical treatment resulted in a lower degree of symptoms. Increasing age was a strong predictor of reduced heel-rise height, and an increase in age of 10 years reduced the expected heel-rise height by approximately 8%. A higher BMI was also a strong predictor of a greater degree of symptoms, and a 5-unit higher BMI predicted a reduction of approximately 10 points in the ATRS. CONCLUSION: The present study identified important possible predictors of outcome. Despite having a wide range of clinically relevant variables, the models had a limited ability to predict the final individual outcome. In general, the models appear to be better at predicting function than symptoms.

Darexaban (YM150) versus enoxaparin for the prevention of venous thromboembolism after total hip arthroplasty: a randomised phase IIb dose confirmation study (ONYX-3).

This double-blind, double-dummy, randomised, phase IIb study (NCT00902928) evaluated different dosing regimens of darexaban compared with enoxaparin (randomised 1:1:1:1:1 to 15 mg twice daily [bid], 30 mg once daily [qd], 30 mg bid or 60 mg qd or enoxaparin 40 mg qd) in patients undergoing elective total hip arthroplasty. Patients, investigators, pharmacists and sponsor were all blinded to treatment allocation. Darexaban administration started 6-10 hours (h) post-surgery. Enoxaparin 40 mg qd administration started 12 ± 2 h before surgery. Treatment continued for 35 days. Bilateral venography was performed on Day 10 ± 2. The primary efficacy outcome was total VTEs (composite of proximal/distal deep-vein thrombosis, pulmonary embolism) or death, at Day 12. Total VTE rates were similar across all groups. There was no apparent difference in efficacy between once- and twice-daily darexaban (odds ratio [OR] 1.00; 95% confidence interval [CI] 0.71-1.42; p=0.988), or total daily dose (30 mg/day vs 60 mg/day; OR 0.81; 95% CI 0.57-1.15; p=0.244). There was no significant difference in major and/or clinically relevant non-major bleeding between darexaban qd or bid, or between total daily doses of 30 mg or 60 mg, and also for any dosing regimen of darexaban vs enoxaparin. Darexaban was well tolerated, without signs of liver toxicity. In conclusion, darexaban, administered qd or bid, and at total daily doses of 30 mg or 60 mg, appears to be effective for VTE prevention and was well tolerated. Data suggest no significant differences between a once- or twice-daily dosing regimen.

Stable surgical repair with accelerated rehabilitation versus nonsurgical treatment for acute Achilles tendon ruptures: a randomized controlled study.

BACKGROUND: The optimal treatment for acute Achilles tendon ruptures is still a subject of debate. Early loading of the tendon is a factor that has been shown to be beneficial to recovery and to minimize complications. The main outcome of previous studies has been complications such as reruptures and deep infections, without focusing on the functional outcome relevant to the majority of patients who do not experience these complications. PURPOSE: To evaluate whether stable surgical repair and early loading of the tendon could improve patient-reported outcome and function after an acute Achilles tendon rupture. STUDY DESIGN: Randomized controlled trial; Level of evidence, 1. METHODS: A total of 100 patients (86 men, 14 women; mean age, 40 years) with an acute total Achilles tendon rupture were randomized to either surgical treatment, including an accelerated rehabilitation protocol, or nonsurgical treatment. The primary outcome was the Achilles tendon Total Rupture Score (ATRS). The patients were evaluated at 3, 6, and 12 months for symptoms, physical activity level, and function. RESULTS: There were no significant differences between the groups in terms of symptoms, physical activity level, or quality of life. There was a trend toward improved function in surgically treated patients; the results were significantly superior when assessed by the drop countermovement jump (95% CI, 0.03-0.15; P = .003) and hopping (95% CI, 0.01-0.33; P = .040). No reruptures occurred in the surgical group, while there were 5 in the nonsurgical group (P = .06). There were 6 superficial infections in the surgically treated group; however, these superficial infections had no bearing on the final outcome. Symptoms, reduced quality of life, and functional deficits still existed 12 months after injury on the injured side in both groups. CONCLUSION: The results of the present study demonstrate that stable surgical repair with accelerated tendon loading could be performed in all (n = 49) patients without reruptures and major soft tissue-related complications. However, this treatment was not significantly superior to nonsurgical treatment in terms of functional results, physical activity, or quality of life.

Novel oral anticoagulants for thromboprophylaxis after orthopaedic surgery.

The direct thrombin inhibitor, dabigatran, and the selective factor Xa inhibitors, rivaroxaban and apixaban, are new oral anticoagulants that are approved in many countries for prevention of venous thromboembolism in patients undergoing elective hip or knee arthroplasty. All have a rapid onset of action, a low potential for food and drug interactions and a predictable anticoagulant effect that obviates the need for routine coagulation monitoring. These agents offer a convenient alternative to conventional anticoagulant drug regimens, including parenteral low-molecular-weight heparins and fondaparinux, and oral adjusted-dose vitamin K antagonists, for the prevention of venous thromboembolism in this surgical setting. This review summarizes the pharmacology, clinical trial results, bleeding risk and practical use of these new oral anticoagulants in clinical orthopaedic practice. Potential issues to be considered when using these oral anticoagulants include renal impairment, potential drug interactions, neuraxial anaesthesia and management of bleeding.

Detection of slow-cycling and stem/progenitor cells in different regions of rat Achilles tendon: response to treadmill exercise.

PURPOSE: Tendons generally exhibit poor healing capacity, probably due to slow cell regeneration potential and low vascularization. The potential to regenerate may partly be due to activation of stem/progenitor cells localized in the tendon or its vicinity. In the present study, we attempted to determine where in the rat Achilles tendon stem/progenitor cells reside and to investigate the effect of exercise on cell proliferation in the in vivo situation. METHOD: We used bromodeoxyuridine (BrdU) labelling to investigate proliferation and label-retaining cells (i.e. slow-cycling cells) in non-exercised and exercised rats, in combination with immunostaining of the stem cell marker nucleostemin. Rat Achilles tendons were harvested 14, 28, 56 and 105 days after BrdU administration. RESULTS: We found the proportion of stem/progenitor cells to be twice as high in the distal tendon (DT) compared with the mid/proximal tendon (MPT) and that paratenon/endotenon regions appear to host a pool of existing stem/progenitor cells. Exercise increased the BrdU-stained cell population after 14 days only (DT region p = 0.032, MPT p = 0.065), indicating effect mainly on more differentiated cells, since the nucleostemin-positive cells (i.e. stem/progenitor cells) remained unaffected in the intact Achilles tendon. CONCLUSION: Stem/progenitor cells exist in several areas of the rat Achilles tendon which implies a possible stem cell regeneration pool of different origins. The distal region has twice the amount of stem/progenitor cells compared with the mid/proximal region, indicating a potentially higher stem cell activity in this tissue. Daily moderate exercise (treadmill running) mainly improves in vivo cell proliferation in rapidly proliferating cells, whereas the stem/progenitor pool remains constant.

The Ilizarov external fixator--a useful alternative for the treatment of proximal tibial fractures. A prospective observational study of 30 consecutive patients.

BACKGROUND: In dislocated proximal tibial fractures, the most frequently used treatment is ORIF with screws and plates. Minimally-invasive techniques using external fixation are an alternative. The aim of this study was to analyse the clinical and radiological results using the Ilizarov technique in both uni- and bicondylar tibial fractures. METHODS: Thirty consecutive patients with isolated fractures of the proximal tibia were treated with the Ilizarov technique, 11 Schatzker I-IV with 2-3 rings and 19 Schatzker V-VI with 3-4 tibial rings and a femoral, hinged, two-ring extension. Unrestricted weight-bearing was allowed. Pre and post-operatively, conventional radiographs, computerized tomography scans, post-operative pain assessments and complications were evaluated. The knee function was evaluated with the EQ-5D, NHP and KOOS scores, as well as self-appraisal. RESULTS: All the fractures healed. Twenty-five patients achieved a range of motion better than 10-100º. The type I-IV fractures had a shorter operating time and hospital stay, as well as better knee flexion, and the self-appraisal indicated that they tolerated the treatment better. Pin infections occurred in 4% of the pin sites, but only two patients required debridement. Two patients developed compartment syndrome and underwent fasciotomy. No patient complained of functional knee instability. Two patients underwent a total knee arthroplasty because of residual pain. The overall result was judged as satisfactory in twenty-seven patients. CONCLUSIONS: The Ilizarov method produces a good clinical outcome and is a valuable treatment alternative in proximal tibial fractures of all types.

Treatment of distal tibial fractures with the Ilizarov external fixator--a prospective observational study in 39 consecutive patients.

BACKGROUND: The management of displaced distal tibial fractures is still controversial. The different internal fixation techniques are often burdened by relatively high complication rates. Minimally invasive techniques with ring fixators have been introduced as an alternative allowing immediate reduction and stabilization, avoiding a staged protocol. The aim of this prospective study was to analyze the clinical and radiographic outcome the Ilizarov technique in patients with distal metaphyseal tibial fractures, with or without intra-articular involvement. METHODS: Thirty-nine consecutive patients with isolated fractures treated with the Ilizarov technique were followed prospectively for one year. Depending on the type of fracture, 4 or 5 rings were used, in some cases with additional foot extension. Unrestricted weight-bearing was allowed in all cases. Pre- and post-operatively conventional radiographs, post-operative pain assessment and complications were evaluated. The function was evaluated clinically and with self-appraisal protocols: EQ-5D, NHP and FAOS. RESULTS: No patient developed compartment syndrome or deep venous thrombosis. Pin infections were frequent, but they were mostly superficial and were treated with antibiotics and/or the removal of isolated pins. Two patients required debridement. One of them had a deep infection and developed a residual deformity which was corrected and healed after re-operation. Another patient had a severe residual deformity. The fixator was removed after a median period of 16 weeks (range 11-30). The radiological results were poor in 5 patients but the overall self-appraisal showed satisfactory results in 36 patients. CONCLUSIONS: The Ilizarov method allowed early definitive treatment with a low complication rate and a good clinical outcome.