Oral thrombin inhibitor dabigatran etexilate vs North American enoxaparin regimen for prevention of venous thromboembolism after knee arthroplasty surgery

Dabigatran, an oral once-daily unmonitored thrombin inhibitor, has been tested elsewhere using enoxaparin 40 mg once daily. We used the North American enoxaparin 30 mg BID regimen as the comparator. This was a double-blind, centrally randomized trial. Unilateral total knee arthroplasty patients were randomized to receive oral dabigatran etexilate 220 or 150 mg once daily, or enoxaparin 30 mg SC BID after surgery, blinded. Dosing stopped at contrast venography, 12 to 15 days after surgery. Among 1896 patients, dabigatran 220 and 110 mg showed inferior efficacy to enoxaparin (venous thromboembolism rates of 31% [P = .02 vs enoxaparin], 34% [P < .001 vs enoxaparin], and 25%, respectively). Bleeding rates were similar, and no drug-related hepatic illness was recognized. Dabigatran, effective compared to once-daily enoxaparin, showed inferior efficacy to the twice-daily North American enoxaparin regimen, probably because of the latter's more intense and prolonged dosing.     

Patterns of recurrence after sentinel lymph node biopsy for cutaneous melanoma

BACKGROUND: Previous sentinel lymph node (SLN) studies for cutaneous melanoma have shown that the SLN accurately reflects the nodal status of the corresponding nodal basin. However, there are few long-term studies that describe recurrence site patterns, predictors for recurrence, and overall survival and disease-free survival after SLN biopsy. METHODS: A retrospective review of patients over a 6-year period was performed to determine patient outcomes and the patterns of recurrence. In all cases, Tc-99 sulfur colloid along with isosulfan blue dye was injected at the primary melanoma site. After resection, the SLN was serially sectioned and evaluated by hematoxylin and eosin staining and immunohistochemistry. RESULTS: One hundred ninety-eight patients were identified who underwent SLN biopsy for cutaneous melanoma including T1 (n = 21), T2 (n = 88), T3 (n = 75), and T4 (n = 14) primary tumors. Of these patients, 38 had a positive SLN. Of the 38 patients with a positive SLN (mean follow-up 38 months), recurrent disease was identified in 10 (26.3%) at a mean interval of 14.2 months. The site of first recurrence was distant (n = 4) and local (n = 6). Regional lymphatic basin recurrence was not identified. Of the 160 patients with a negative SLN (mean follow-up 50 months), recurrent disease was identified in 16 (10.0%) at a mean interval of 31.3 months. The site of first recurrence was systemic (n = 11), local (n = 4), and nodal (n = 1). Overall survival and disease-free survival for patients with a positive SLN at 55 months was 53.3% and 47.7% respectively, while overall survival and disease-free survival for patients with a negative SLN at 53 months was 92.2% and 87.7% respectively (P <0.01). Univariate and multivariate analysis of the entire cohort (n = 198) identified primary tumor depth and positive SLN status as significant predictors of recurrence. CONCLUSIONS: The incidence of nodal basin recurrence after SLN biopsy was found to be 0.6%. Primary tumor depth and pathological status of the SLN are significant predictors of local and systemic recurrence. Long-term follow-up indicates that patients with a positive SLN clearly recur sooner and have decreased overall survival than those with a negative SLN.     

Differences in Systemic Opioid Use Do Not Explain Increased Fever Incidence in Parturients Receiving Epidural Analgesia

Background: It has been hypothesized that an increased incidence of fever in patients receiving epidural analgesia might result not from epidural per se, but rather from the antipyretic effect of opioids preferentially administered to women in the no-epidural group. If this were the case, then one would expect the incidence of fever in parturients who did not receive systemic opioids to be independent of whether they received epidural analgesia.

Methods: Using a cohort study design, the authors evaluated the records of 1,233 nulliparous patients whose labor analgesia was managed with (1) no medication (N = 170); (2) 10 mg intravenous systemic nalbuphine plus 10 mg intramuscular every 3 to 4 h as required (N = 327); (3) epidural analgesia with continuous infusion of 0.125% bupivacaine with 2 [mu]g/ml fentanyl (N = 278); or (4) patients who received both systemic nalbuphine and epidural analgesia (N = 458). Fever was diagnosed if the maximum temperature during labor exceeded 100.4[degrees]F (38[degrees]C).

Results: The incidence of fever did not differ according to nalbuphine administration for women not receiving epidural analgesia (1% no nalbuphine, 0.3% with nalbuphine, P = 0.27) or for women receiving epidural analgesia (17% no nalbuphine, 17% with nalbuphine, P = 1.0). However, the incidence of fever differed significantly between patients who received no analgesia as compared to those who received epidural analgesia alone (1%vs. 17%, P = 10-6). Controlling for confounding did not alter these associations.     

Comparison of the responsiveness of the SF-36 and WOMAC in patients undergoing total hip arthroplasty

This study examines the responsiveness of the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) and Short Form-36 (SF-36) in patients undergoing total hip arthroplasty. Eighty-nine patients completed the WOMAC and SF-36 preoperatively and postoperatively. Standardized response means (SRMs) and effect sizes (ES) were used to measure responsiveness. Mean follow-up was 17 months. The SRMs for the WOMAC ranged from -0.93 to -1.49, and the ES ranged from -1.02 to -1.53. The SRMs for the SF-36 ranged from 0.22 to 1.64, and the ES ranged from 0.20 to 1.97. The highest values occurred with the physical functioning, bodily pain, and Physical Component Summary Scales. This study demonstrates a similar level of responsiveness of the WOMAC and several components of the SF-36. This suggests that the isolated use of the SF-36 may be adequate to monitor outcomes after total hip arthroplasty. There may still be a role for the WOMAC when comparing outcomes of specific designs or techniques of total hip arthroplasty.     

Vertebroplasty and kyphoplasty for the management of osteoporotic vertebral compression fractures

Osteoporotic vertebral compression fractures have previously been treated nonoperatively given the tremendous morbidity associated with open fixation in elderly patients who often have multiple medical comorbidities. With the advent of percutaneous vertebral augmentation techniques, these fractures can now be stabilized using minimally invasive surgical techniques while maintaining a relatively safe risk profile. Vertebroplasty and kyphoplasty provide immediate pain relief in the great majority of patients who have painful, osteoporotic vertebral compression fractures. The balloon used in kyphoplasty may allow for improved height restoration, cavity creation, and decreased cement extravasation rates. The authors discuss the procedural steps, advantages and disadvantages, and results of each technique, recognizing that prospective, randomized controlled studies are necessary to objectively compare the two techniques.     

Lentiviral-mediated BMP-2 gene transfer enhances healing of segmental femoral defects in rats

The objective of the present study was to assess the ability of bone marrow cells expressing BMP-2 created via lentiviral gene transfer to heal a critical sized femoral defect in a rat model. Femoral defects in Lewis rats were implanted with 5x10(6) rat bone marrow stromal cells (RBMSC) transduced with a lentiviral vector containing either the BMP-2 gene (Group I), the enhanced green fluorescent protein (LV-GFP) gene (Group IV), or RBMSC alone (Group V). We also included femoral defects that were treated with BMP-2-producing RBMSC transduced with lentivirus, 8 weeks after infection (Group III), and a group with 1x10(6) RBMSC transduced with a lentiviral vector with the BMP-2 gene (Group II). All defects (10/10) treated in Group I healed at 8 weeks compared with none of the femora in the control groups (Groups IV and V). In Group II, only one out of 10 femora healed. In Group III, 5 out of 10 femora healed. Significantly higher amounts of in vitro BMP-2 protein production were detected in Groups I, II, and III when compared to that of the control groups (p<0.05). Histomorphometric analysis revealed significantly greater total bone volume in defects in Group I and III when compared to control specimens (p<0.003). Biomechanical testing revealed no significant differences in the healed defects in Groups I and III when compared to intact, nonoperated femora with respect to peak torque and torque to failure. Our results indicate that BMP-2-producing RBMSC created through lentiviral gene transfer have the capability of inducing long-term protein production in vitro and producing substantial new bone formation in vivo.     

Hyperbaric oxygen therapy improves angiogenesis and bone formation in critical sized diaphyseal defects

Besides the use of autologous bone grafting several osteoconductive and osteoinductive methods have been reported to improve bone healing. However, persistent non‐union occurs in a considerable number of cases and compromised angiogenesis is suspected to impede bone regeneration. Hyperbaric oxygen therapy (HBO) improves angiogenesis. This study evaluates the effects of HBO on bone defects treated with autologous bone grafting in a bone defect model in rabbits. Twenty‐four New‐Zealand White Rabbits were subjected to a unilateral critical sized diaphyseal radius bone defect and treated with autologous cancellous bone transplantation. The study groups were exposed to an additional HBO treatment regimen. Bone regeneration was evaluated radiologically and histologically at 3 and 6 weeks, angiogenesis was assessed by immunohistochemistry at three and six weeks. The additional administration of HBO resulted in a significantly increased new bone formation and angiogenesis compared to the sole treatment with autologous bone grafting. These results were apparent after three and six weeks of treatment. The addition of HBO therapy to autologous bone grafts leads to significantly improved bone regeneration. The increase in angiogenesis observed could play a crucial role for the results observed. © 2015 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 33:513–520, 2015.     

Representative dynamic ranges of spinal alignment during gait in patients with mild and severe adult spinal deformities

BACKGROUND CONTEXTSurgical correction strategies for adult spinal deformity (ASD) relies heavily on radiographic alignment goals, however, there is often debate regarding degree of correction and how static alignment translates to physical ability in daily life. Kinematic analysis has the potential to improve the concept of ideal spinal alignment by providing clinically meaningful estimates of dynamic changes in spinal alignment during activities of daily life.PURPOSEEstimate representative dynamic ranges of spinal alignment during gait among ASD patients using 3D motion tracking; compare dynamic alignment between mild and severe deformity patients and to healthy adults.STUDY DESIGN/SETTINGRetrospective review at a single institution.PATIENT SAMPLEFifty-two ASD patients and 46 healthy adults.OUTCOME MEASURESRadiographic alignment, kinematic spine motion, spatiotemporal gait measures, patient reported outcomes (VAS pain, ODI, SRS-22r).METHODSSpinal alignment was assessed radiographically and during standing and overground walking tests. Dynamic alignment was initialized by linking radiographic alignment to kinematic alignment during standing and at initial heel contact during gait. Dynamic changes in maximums and minimums during gait were made relative to initial heel contact for each gait cycle. Total range-of-motion (RoM) was measured for both ASD and healthy subjects. Dynamic alignment measures included coronal and sagittal vertical axes (CVA, SVA), T1 pelvic angle (TPA), lumbar lordosis (LL), and pelvic tilt (PT). ASD patient's deformities were classified as either Mild or Severe based on the SRS-Schwab ASD classification.RESULTSSevere ASD patients had significantly larger dynamic maximum and minimums for SVA, TPA, LL, and PT (all p<.05) compared with Mild ASD patients. ASD patients exhibited little difference in dynamic alignment compared with healthy subjects. Only PT had a significant difference in dynamic RoM compared with healthy (p<.001).CONCLUSIONSMild and Severe ASD patients exhibited similar global dynamic alignment measures during gait and had comparable RoM to healthy subjects except with greater PT and reduced spatiotemporal performance which may be key compensatory mechanisms for dynamic stabilization.