Jonathan Riboh

Transtibial Versus Independent Drilling Techniques for Anterior Cruciate Ligament Reconstruction A Systematic Review, Meta-analysis, and Meta-regression

Background: While numerous cadaveric, in vivo, and clinical studies have compared transtibial and independent drilling of femoral tunnels during anterior cruciate ligament reconstruction, there is no evidence-based consensus on which technique affords the best outcome. Hypothesis: There is no difference in clinical outcome between transtibial and independent drilling of femoral tunnels. Study Design: Systematic review with meta-analysis and meta-regression. Methods: Cadaveric, in vivo, and clinical studies comparing transtibial and independent drilling techniques were systematically identified. A qualitative synthesis of nonrandomized studies and meta-analysis of randomized controlled trials (RCTs) were performed. In addition, a meta-regression analysis of RCTs that did not directly compare drilling techniques was performed. Results: A total of 49 studies were included in the qualitative review, and 15 were included in the meta-analysis; 22 studies were included in the meta-regression. In biomechanical studies, independent drilling placed the center of the femoral tunnel closer to the center of the femoral footprint (mean difference, 2.69 mm; 95% CI, 0.46-4.92; P < .00001). Independent drilling reduced anterior tibial translation with the Lachman examination (mean difference, 2.2 mm; 95% CI, 0.34-4.07; P = .02), 134 N of anterior load (mean difference, 1 mm; 95% CI, 0.29-1.71; P = .006), and simulated pivot shift (mean difference, 3.36 mm; 95% CI, 1.88-4.85; P < .00001). The meta-analysis showed improved Lysholm scores with independent drilling (mean difference, −0.62 points; 95% CI, −1.09 to −0.55; P = .009), although the clinical relevance of this small difference is questionable. There were no significant differences in International Knee Documentation Committee (IKDC) objective scores or Tegner scores between groups. With the meta-regression, there were no significant differences in failure rates or IKDC objective scores. Conclusion: While there are biomechanical data suggesting improved knee stability and more anatomic graft placement with independent drilling, no significant clinical differences were found between the 2 techniques. Clinical Relevance: The current evidence shows that transtibial and independent drilling techniques have equivalent clinical outcomes at short-term to midterm follow-up. The long-term effects of subtle differences in tunnel position and postoperative knee kinematics should be further studied in dedicated, prospective cohort and randomized studies.

Prospective Multicenter Phase II Trial of Systemic ADH-1 in Combination With Melphalan via Isolated Limb Infusion in Patients With Advanced Extremity Melanoma

PURPOSE Isolated limb infusion (ILI) with melphalan (M-ILI) dosing corrected for ideal body weight (IBW) is a well-tolerated treatment for patients with in-transit melanoma with a 29% complete response rate. ADH-1 is a cyclic pentapeptide that disrupts N-cadherin adhesion complexes. In a preclinical animal model, systemic ADH-1 given with regional melphalan demonstrated synergistic antitumor activity, and in a phase I trial with M-ILI it had minimal toxicity. PATIENTS AND METHODS Patients with American Joint Committee on Cancer (AJCC) stage IIIB or IIIC extremity melanoma were treated with 4,000 mg of ADH-1, administered systemically on days 1 and 8, and with M-ILI corrected for IBW on day 1. Drug pharmacokinetics and N-cadherin immunohistochemical staining were performed on pretreatment tumor. The primary end point was response at 12 weeks determined by Response Evaluation Criteria in Solid Tumors (RECIST) criteria. RESULTS In all, 45 patients were enrolled over 15 months at four institutions. In-field responses included 17 patients with complete responses (CRs; 38%), 10 with partial responses (22%), six with stable disease (13%), eight with progressive disease (18%), and four (9%) who were not evaluable. Median duration of in-field response among the 17 CRs was 5 months, and median time to in-field progression among 41 evaluable patients was 4.6 months (95% CI, 4.0 to 7.1 months). N-cadherin was detected in 20 (69%) of 29 tumor samples. Grade 4 toxicities included creatinine phosphokinase increase (four patients), arterial injury (one), neutropenia (one), and pneumonitis (one). CONCLUSION To the best of our knowledge, this phase II trial is the first prospective multicenter ILI trial and the first to incorporate a targeted agent in an attempt to augment antitumor responses to regional chemotherapy. Although targeting N-cadherin may improve melanoma sensitivity to chemotherapy, no difference in response to treatment was seen in this study.

Analysis of the Complications of Palmar Plating Versus External Fixation for Fractures of the Distal Radius

PURPOSE To evaluate whether there was a difference in complication rates in our patients treated with external fixation versus volar plating of distal radius fractures. We also looked for a difference in radiographic results; in the clinical outcomes of flexion, extension, supination, pronation, and grip strength; and in scores on the visual analog scale (VAS) for pain and the Disabilities of the Arm, Shoulder, and Hand (DASH) questionnaire. METHODS We reviewed 115 patients with comminuted intrarticular distal radius fractures. Of those patients, 59 were treated with external fixation and 56 with volar plate fixation. Postoperative radiographs, range of motion, and grip strength were measured; DASH and VAS pain questionnaires were administered; and complications were documented. RESULTS The external fixation group had a significantly higher overall complication rate. In the volar plate group, there were more tendon and median nerve complications, but this difference was not significant. Radiographically, the external fixator group demonstrated radial shortening of 0.7 mm, whereas the volar plate group demonstrated 0.3 mm of radial shortening during the postoperative period. There were no significant differences between the groups in the measurement of scapholunate angle or palmar tilt. The mean DASH score at final follow-up was 32 in the external fixation group and 17 in the volar plate group, which was statistically significant. The final VAS scores were statistically different at 3.1 for the external fixation group and 1.1 for the volar plate group. On physical examination, the volar plate group had significantly better arc of motion in pronation-supination and flexion-extension and better grip strength. CONCLUSIONS In the patients we studied, volar plate fixation has an overall decreased incidence of complications and significantly better motion in flexion-extension and supination-pronation compared to external fixation. Volar plate fixation also has less radial shortening than the external fixation group, yet the absolute difference in magnitude of ulnar variance was only 1.4 mm, calling into question the clinical significance of this difference. Patients with volar plating also have better pain and functional outcomes and better grip strength. TYPE OF STUDY/LEVEL OF EVIDENCE Therapeutic III.

Flexor tendon tissue engineering: acellularized and reseeded tendon constructs.

Background: Tissue engineering of flexor tendons requires scaffolds with adequate strength and biocompatibility. The biomechanical properties of acellularized and reseeded flexor tendon scaffolds are unknown. Acellularized tendons and reseeded constructs were tested to determine whether the treatment process had altered their biomechanical properties. Methods: Rabbit flexor tendons were acellularized using a freeze-thaw cycle followed by trypsin and Triton-X treatment. Complete acellularization of the tendon samples was confirmed by histology and by attempting to obtain viable cells by trypsin treatment of acellularized tendon. Reseeded constructs were obtained by incubating acellularized tendons in a tenocyte suspension. Tensile testing was performed to compare the ultimate tensile stress and elastic modulus of acellularized tendons and reseeded flexor tendon constructs to control flexor tendons. Results: The treatment protocol successfully acellularized flexor tendons. No cells were seen within the tendon on histologic assessment, and no viable cells could be obtained from acellularized tendon. Acellularized tendon was successfully reseeded with tenocytes, although cell adhesion was limited to the surface of the tendon scaffold. Tensile testing showed that acellularized tendon had the same ultimate stress and elastic modulus as normal tendons. Reseeded tendons had the same elastic modulus as normal tendons, but hind-paw tendon constructs showed a decrease in ultimate stress compared with normal tendons (50.09 MPa versus 66.01 MPa, p = 0.026). Conclusions: Acellularized flexor tendons are a potential high-strength scaffold for flexor tendon tissue engineering. This approach of acellularization and reseeding of flexor tendons may provide additional intrasynovial graft material for hand reconstruction.

Outcomes of sutureless gastroschisis closure

INTRODUCTION A new technique of gastroschisis closure in which the defect is covered with sterile dressings and allowed to granulate without suture repair was first described in 2004. Little is known about the outcomes of this technique. This study evaluated short-term outcomes from the largest series of sutureless gastroschisis closures. METHODS AND PATIENTS A retrospective case control study of 26 patients undergoing sutureless closure between 2006 and 2008 was compared to a historical control group of 20 patients with suture closure of the abdominal fascia between 2004 and 2006. Four major outcomes were assessed: (1) time spent on ventilator, (2) time to initiating enteral feeds, (3) time to discharge from the neonatal intensive care unit, and (4) rate of complications. RESULTS In multivariate analysis, sutureless closure of gastroschisis defects independently reduced the time to extubation as compared to traditional closure (5.0 vs 12.1 days, P = .025). There was no difference in time to full enteral feeds (16.8 vs 21.4 days, P = .15) or time to discharge (34.8 vs 49.7 days, P = .22) with sutureless closure. The need for silo reduction independently increased the time to extubation (odds ratio, 4.2; P = .002) and time to enteral feeds (odds ratio, 5.2; P < .001). Small umbilical hernias were seen in all patients. CONCLUSION Sutureless closure of uncomplicated gastroschisis is a safe technique that reduces length of intubation and does not significantly alter the time required to reach full enteral feeds or hospital discharge.

Optimization of flexor tendon tissue engineering with a cyclic strain bioreactor.

PURPOSE Mechanical manipulation of cultured tendon cells can enhance cell proliferation and matrix production. This study aims to determine the bioreactor strain patterns (amplitude, frequency, and on/off ratio) that favor cellular proliferation, promote collagen production, and maintain morphology in candidate cell lines cultured for flexor tendon tissue engineering, including multipotent stromal cells. METHODS We studied epitenon tenocytes (Es), sheath fibroblasts (Ss), bone marrow-derived mesenchymal stem cells (BMSCs), and adipoderived stem cells (ASCs). We examined the effects of 3 patterns of cyclic uniaxial strain on cell proliferation, collagen I production, and cell morphology. RESULTS Adipoderived stem cells (33% adhesion) and Ss (29%) adhered more strongly to bioreactor membranes than did Es (15%) and BMSCs (7%), p=.04. Continuous cyclic strain (CCS, 8%, 1 Hz) inhibited cell proliferation (p=.01) and increased per-cell collagen production (p=.04) in all cell types. Intermittent cyclic strain (4%, 0.1 Hz, 1 hour on/5 hours off) increased proliferation in ASCs (p=.06) and Ss (p=.04). Intermittent cyclic strain (4%, 0.1 Hz, 1 hour on/2 hours off) increased total collagen production by 25% in ASCs (p=.004) and 20% in Ss (p=.05). Cyclic strain resulted in cell alignment perpendicular to the strain axis, cytoskeletal alignment, and nuclear elongation. These morphological characteristics are similar to those of tenocytes. CONCLUSIONS These results demonstrate that intermittent cyclic strain can increase cell proliferation, promote collagen I production, and maintain tenocyte morphology in vitro. Use of a cell bioreactor might accelerate the in vitro stage of tendon tissue engineering.

Bioactive Sutures for Tendon Repair: Assessment of a Method of Delivering Pluripotential Embryonic Cells

PURPOSE Pluripotential embryonic cells may be seeded onto sutures intended for tendon repair. These cells may be influenced to adhere to suture material using adhesion substrates, and furthermore, these cells may remain in culture attached to those sutures. These cell-impregnated sutures may be useful for promoting healing of tendon repairs. METHODS Ten-centimeter segments of 4-0 sutures (FiberWire) were coated overnight with 10 microg/mL fibronectin, 10 microg/mL poly-l-lysine, or phosphate-buffered saline. The sutures were placed in dishes and covered with a suspension of C3H10T1/2 cells at concentrations of 1 x 10(6), 2 x 10(6), or 4 x 10(6) cells for 24 hours. The sutures were then placed into low adhesion polypropylene tubes with Dulbeccos modified Eagles medium and 10% fetal bovine serum for 7 days. The presence of viable cells on these sutures was assessed by the colorimetric Alamar blue cell proliferation assay. Spectrophotometry was used to quantify the relative amount of cell proliferation across the experimental groups. The sutures were also visually inspected using phase-contrast light microscopy. RESULTS Our results show that at all seeding densities (1 x 10(6), 2 x 10(6), and 4 x 10(6) cells), the suture segments coated with poly-l-lysine and fibronectin showed a significant increase in C3H10T1/2 cell adhesion. Coating the suture with poly-l-lysine increased the adherent cell number to 17% of the initial seeding concentration compared with 2% for the control. Fibronectin coating increased the number of adherent viable cells present to 6.6%. CONCLUSIONS Pluripotential embryonic cells may be seeded onto sutures, adhere, and survive in culture. Coating sutures with poly-l-lysine and fibronectin offers significant improvement in retention of viable cells. This technique may be a useful adjunct for future tendon healing studies.

Humeral Head Reconstruction With Osteochondral Allograft Transplantation

PURPOSE To synthesize, in a systematic review, the available clinical evidence of osteochondral allograft transplants for large osteochondral defects of the humeral head. METHODS The Medline, Embase, and Cochrane databases were searched for studies reporting clinical or radiographic outcomes of osteochondral allograft transplantation for humeral head defects. Descriptive statistics were provided for all outcomes. After checking for data normality, we compared postoperative and preoperative values using the Student t test. RESULTS We included 12 studies (8 case reports and 4 case series) in this review. The study group consisted of 35 patients. The mean age was 35.4 ± 18.1 years; 77% of patients were male patients. Thirty-three patients had large Hill-Sachs lesions due to instability, 1 had an osteochondritis dissecans lesion, and 1 had an iatrogenic lesion after resection of synovial chondromatosis. The mean lesion size was 3 ± 1.4 cm (anteroposterior) by 2.25 ± 0.3 cm (medial-lateral), representing on average 40.5% ± 4.73% of the native articular surface. Of the 35 patients, 3 received a fresh graft, with all others receiving frozen grafts. Twenty-three femoral heads, 10 humeral heads, and 2 sets of osteochondral plugs were used. The mean length of follow-up was 57 months. Significant improvements were seen in forward flexion at 6 months (68° ± 18.1°, P < .001), forward flexion at 12 months (83.42° ± 18.3°, P < .001), and external rotation at 12 months (38.72° ± 18.8°, P < .001). American Shoulder and Elbow Surgeons scores improved by 14 points (P = .02). Radiographic studies at final follow-up showed allograft necrosis in 8.7% of cases, resorption in 36.2%, and glenohumeral arthritic changes in 35.7%. Complication rates were between 20% and 30%, and the reoperation rate was 26.67%. Although only 3 patients received fresh allografts, there were no reports of graft resorption, necrosis, or arthritic changes in these patients. CONCLUSIONS Humeral head allograft-most commonly used in the setting of large Hill-Sachs lesions due to instability-has shown significant improvements in shoulder motion and American Shoulder and Elbow Surgeons scores as far as 1 year postoperatively. Return-to-work rates and satisfaction levels are high after the intervention. Complication and reoperation rates are substantial, although it is possible that use of fresh allograft tissue may result in less resorption and necrosis. LEVEL OF EVIDENCE Level V, systematic review of Level IV and V studies.

Myofiber angle distributions in the ovine left ventricle do not conform to computationally optimized predictions

Recent computational models of optimized left ventricular (LV) myofiber geometry that minimize the spatial variance in sarcomere length, stress, and ATP consumption have predicted that a midwall myofiber angle of 20 degrees and transmural myofiber angle gradient of 140 degrees from epicardium to endocardium is a functionally optimal LV myofiber geometry. In order to test the extent to which actual fiber angle distributions conform to this prediction, we measured local myofiber angles at an average of nine transmural depths in each of 32 sites (4 short-axis levels, 8 circumferentially distributed blocks in each level) in five normal ovine LVs. We found: (1) a mean midwall myofiber angle of -7 degrees (SD 9), but with spatial heterogeneity (averaging 0 degrees in the posterolateral and anterolateral wall near the papillary muscles, and -9 degrees in all other regions); and (2) an average transmural gradient of 93 degrees (SD 21), but with spatial heterogeneity (averaging a low of 51 degrees in the basal posterior sector and a high of 130 degrees in the mid-equatorial anterolateral sector). We conclude that midwall myofiber angles and transmural myofiber angle gradients in the ovine heart are regionally non-uniform and differ significantly from the predictions of present-day computationally optimized LV myofiber models. Myofiber geometry in the ovine heart may differ from other species, but model assumptions also underlie the discrepancy between experimental and computational results. To test the predictive capability of the current computational model would we propose using an ovine specific LV geometry and comparing the computed myofiber orientations to those we report herein.

Inside-Out Versus All-Inside Repair of Isolated Meniscal Tears: An Updated Systematic Review.

Background: Meniscal tears are common in the young, active population. In this group of patients, repair is advised when possible. While inside-out repair remains the standard technique, recent advances in all-inside repair devices have led to a growth in their popularity. Previous reviews on the topic have focused on outdated implants of limited clinical relevance. Purpose: To determine the difference in failure rates, functional outcomes, and complications between inside-out and modern all-inside repairs. Study Design: Systematic review. Methods: A systematic review was registered with PROSPERO and performed following Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) guidelines using the MEDLINE, EMBASE, and Cochrane databases. Inclusion criteria were (1) clinical study reporting on all-inside or inside-out repair, (2) evidence levels 1 to 4, and (3) use of modern all-inside implants for all-inside repairs. Exclusion criteria were (1) use of meniscal arrows or screws and (2) concomitant surgical procedures. Study characteristics, subjects, surgical technique, clinical outcomes, and complications were collected and analyzed. Results: A total of 481 studies were screened and assessed for eligibility, which identified 27 studies for review. Studies defined clinical failure as persistent mechanical symptoms, effusion, or joint line tenderness, while anatomic failure was incomplete or no healing on MRI or second-look arthroscopy. There were no significant differences in clinical or anatomic failure rates between inside-out and all-inside repairs (clinical failure: 11% vs 10%, respectively, P = .58; anatomic failure: 13% vs 16%, respectively, P = .63). Mean ± SD Lysholm and Tegner scores for inside-out repair were 88.0 ± 3.5 and 5.3 ± 1.2, while the respective scores for all-inside repair were 90.4 ± 3.7 and 6.3 ± 1.3. Complications occurred at a rate of 5.1% for inside-out repairs and 4.6% for all-inside repairs. Conclusion: The quality of the evidence comparing inside-out and all-inside meniscal repair remains low, with a majority of the literature being evidence level 4 studies. In this review comparing modern all-inside devices with inside-out repair, no differences were seen in failure rates, functional outcome scores, or complication rates.