Factors affecting lymph node sampling patterns and the impact on survival of lymph node density in patients with Wilms tumor: a Surveillance, Epidemiology, and End Result (SEER) database review.

BACKGROUND: Lymph node (LN) involvement is an important prognostic indicator for patients with Wilms tumor (WT), and there have been previous reports of utilizing LN density (LND = positive LN/LNs examined) as an advanced metric to risk-stratify patients with WT. OBJECTIVE: The purpose of this study was to describe patient characteristics that affect LN yield and assess the effect of LND on the overall survival (OS) in patients with WT, with the expectation that patients with LNDs above a critical cut-point would demonstrate lower OS. STUDY DESIGN: The Surveillance, Epidemiology, and End Result (SEER) database was queried for all patients diagnosed with unilateral WT from 2004 to 2015. Patient and disease characteristics were collected, and Poisson regression was used to identify characteristics correlated with LN yield. LND was calculated for LN-positive patients, and multivariable survival analysis was performed, including patient demographics and LND as variables. RESULTS: 1489 patients with unilateral WT were identified for analysis, 231 (15.51%) of whom were LN-positive. Median patient age at diagnosis was three years (IQR 1-5). On Poisson regression, the year of diagnosis, patient age, tumor size and laterality, and stage were found to impact LN yield. For patients with positive LNs, five-year OS of patients with LNDs above 0.4 was worse than those below 0.4 (76.1% vs 89.6%, p = 0.041). On multivariable analysis, tumor size and LND remained significant predictors of OS. DISCUSSION: Administrative databases such as SEER provide an excellent resource for studying conditions where large patient numbers for analysis are difficult to obtain. Unfortunately, the SEER database is unable to account for every factor that could affect LN sampling patterns. Additionally, favorable vs unfavorable histology is not available in SEER, and SEER utilizes its own staging system, which makes comparison to Children's Oncology Group staging difficult. Despite these limitations, the findings of this study are similar to those previously published using administrative databases analyzing LN sampling patterns and the effect of LND on OS in WT. CONCLUSIONS: Analysis of the SEER database confirms that there are several patient- and disease-specific factors that affect the number of LNs sampled during nephrectomy for WT, and that LND may be a predictor of OS. These findings highlight the need for standardization of LN sampling patterns for pediatric renal tumors and support the investigation of LND in future studies to further risk-stratify WT patients to tailor therapy intensity.

Surgeon-Directed Cost Variation in Isolated Rotator Cuff Repair.

BACKGROUND: As value becomes a larger component of heath care decision making, cost data can be evaluated for regional and physician variation. Value is determined by outcome divided by cost, and reducing cost increases value for patients. "Third-party spend" items are individual selections by surgeons used to perform procedures. Cost data for third-party spend items provide surgeons and hospitals with important information regarding care value, potential cost-saving opportunities, and the total cost of ownership of specific clinical decisions. PURPOSE: To perform a cost review of isolated rotator cuff repair within a regional 7-hospital system and to document procedure cost variation among operating surgeons. STUDY DESIGN: Economic and decision analysis; Level of evidence, 4. METHODS: Current Procedural Terminology (CPT) codes were used to retrospectively identify subjects who received an isolated rotator cuff repair within a 7-hospital system. Cost data were collected for clinically sensitive third-party spend items and divided into 4 cost groups: (1) suture anchors, (2) suture-passing devices and needles, (3) sutures used for cuff repair, and (4) disposable tools or instruments. RESULTS: A total of 62 isolated rotator cuff repairs were performed by 17 surgeons over a 13-month period. The total cost per case for clinically sensitive third-party spend items (in 2015 US dollars) ranged from $293 to $3752 (mean, $1826). Four surgeons had a mean procedure cost that was higher than the data set mean procedure cost. The cost of an individual suture anchor ranged from $75 to $1775 (mean, $403). One disposable suture passer was used, which cost $140. The cost of passing needles ranged from $140 to $995 (mean, $468). The cost per repair suture (used to repair cuff tears) varied from $18 to $298 (mean, $61). The mean suture (used to close wounds) cost per case was $81 (range, $0-$454). A total of 316 tools or disposable instruments were used, costing $1 to $1573 per case (mean, $624). CONCLUSION: This study demonstrates significant cost variation with respect to cost per case and cost of individual items used during isolated rotator cuff repair. Suture anchors represent the most expensive and variable surgeon-directed cost. The wide cost variation seen in all cost categories illustrates both the effect of surgeon choice in procedure cost and the opportunity for significant cost savings in cases of isolated rotator cuff repair. Engaging surgeons in discussion on cost can positively influence the value of care provided to patients if costs can be reduced without affecting the quality of patient outcomes.

Comparison of a novel oxysterol molecule and rhBMP2 fusion rates in a rabbit posterolateral lumbar spine model.

BACKGROUND CONTEXT: The nonunion rate after lumbar spinal fusion is as high as 25%. Recombinant human bone morphogenetic protein 2 (rhBMP2) has been used as a biological adjunct to promote bony fusion. However, recently there have been concerns about BMP2. Oxysterol 133 (Oxy133) has been shown to promote excellent fusion rates in rodent lumbar spine models and offers a potential alternative to rhBMP2. PURPOSE: The purpose of this study was to compare the fusion rate of rhBMP2 and Oxy133 in a randomized controlled trial using a posterolateral lumbar rabbit spinal fusion model. STUDY DESIGN: This was a randomized control animal study. METHODS: Twenty-four male adult white New Zealand rabbits (3-3.5 kg) underwent bilateral posterolateral lumbar spinal fusion at L4-L5. Rabbits were divided into four groups: control (A), 30-µg rhBMP2 (B), 20-mg Oxy133 (C), and 60-mg Oxy133 (D). At 4 weeks, fusion was evaluated by fluoroscopy, and at 8 weeks, the rabbits were sacrificed and fusion was evaluated radiographically, by manual palpation, and with microcomputed tomography. RESULTS: Fusion rates by radiographic analysis at 8 weeks were Group A, 40.0%; Group B, 91.7%; Group C, 91.7%; and Group D, 100%. Evaluation of fusion masses by manual palpation of excised spines after sacrifice showed the following fusion rates: Group A, 0%; Group B, 83.3%; Group C, 83.3%; and Group D, 90%. Microcomputed tomography scanning confirmed these findings. CONCLUSIONS: These findings in a rabbit model demonstrate that both 20- and 60-mg Oxy133 doses promote fusion that is equivalent to fusion induced by 30-µg rhBMP2 and significantly greater than the control group. The present findings confirm that Oxy133 is a promising candidate for therapeutic development as an alternative to rhBMP2 to promote spinal fusion.

A biomechanical comparison of femoral cortical suspension devices for soft tissue anterior cruciate ligament reconstruction under high loads.

BACKGROUND: Graft healing after soft tissue anterior cruciate ligament (ACL) reconstruction requires rigid fixation to allow for soft tissue healing. Cortical suspension devices for femoral fixation should be biomechanically tested under high loads representative of early rehabilitation to evaluate whether they provide sufficient fixation. PURPOSE/HYPOTHESIS: To biomechanically compare current fixed-loop and adjustable-loop cortical suspension devices for soft tissue femoral fixation under high loads. The hypotheses were that there would be significant differences in cyclic displacement between devices, independent of loop type, and that retensioning of the adjustable-loop devices would not significantly alter the biomechanical properties of these devices. STUDY DESIGN: Controlled laboratory study. METHODS: Five different femoral ACL graft cortical suspension devices (3 fixed and 2 adjustable) were compared under high cyclic forces (100-400 N for 1000 cycles) and then pulled to failure at 50 mm/min. In addition, the effect of retensioning after simulated preconditioning was evaluated for the 2 adjustable-loop devices. RESULTS: On average, the least amount of cumulative peak cyclic displacement (mean±SD) was observed for the ENDOBUTTON (1.05±0.05 mm), followed by the RIGIDLOOP (1.09±0.16 mm), XO Button (1.65±0.43 mm), TightRope with retensioning (1.81±0.51 mm), TightRope without retensioning (2.20±0.62 mm), ToggleLoc with retensioning (3.22±1.41 mm), and ToggleLoc without retensioning (3.69±2.39 mm). The ENDOBUTTON displaced significantly less after cyclic loading than all adjustable-loop devices (TightRope and ToggleLoc, both with and without retensioning) and the XO Button. The RIGIDLOOP displaced significantly less than the TightRope without retensioning and ToggleLoc with and without retensioning. There was no significant difference in biomechanical properties after retensioning for both adjustable-loop devices. CONCLUSION: Significant differences were observed between current fixed-loop and adjustable-loop cortical suspension devices for soft tissue femoral fixation when subjected to high loads experienced during rehabilitation. Retensioning did not significantly alter the biomechanical properties of adjustable-loop devices. CLINICAL RELEVANCE: Early rehabilitation protocols subject the graft construct to higher forces than what has been previously tested biomechanically. Biomechanical testing of cortical suspension devices under simulated high rehabilitation loads demonstrated significant differences between devices. Future studies should investigate the clinical implications of these time zero results.

A novel osteogenic oxysterol compound for therapeutic development to promote bone growth: activation of hedgehog signaling and osteogenesis through smoothened binding.

Osteogenic factors are often used in orthopedics to promote bone growth, improve fracture healing, and induce spine fusion. Osteogenic oxysterols are naturally occurring molecules that were shown to induce osteogenic differentiation in vitro and promote spine fusion in vivo. The purpose of this study was to identify an osteogenic oxysterol more suitable for clinical development than those previously reported, and evaluate its ability to promote osteogenesis in vitro and spine fusion in rats in vivo. Among more than 100 oxysterol analogues synthesized, Oxy133 induced significant expression of osteogenic markers Runx2, osterix (OSX), alkaline phosphatase (ALP), bone sialoprotein (BSP), and osteocalcin (OCN) in C3H10T1/2 mouse embryonic fibroblasts and in M2-10B4 mouse marrow stromal cells. Oxy133-induced activation of an 8X-Gli luciferase reporter, its direct binding to Smoothened, and the inhibition of Oxy133-induced osteogenic effects by the Hedgehog (Hh) pathway inhibitor, cyclopamine, demonstrated the role of Hh pathway in mediating osteogenic responses to Oxy133. Oxy133 did not stimulate osteogenesis via BMP or Wnt signaling. Oxy133 induced the expression of OSX, BSP, and OCN, and stimulated robust mineralization in primary human mesenchymal stem cells. In vivo, bilateral spine fusion occurred through endochondral ossification and was observed in animals treated with Oxy133 at the fusion site on X-ray after 4 weeks and confirmed with manual assessment, micro-CT (µCT), and histology after 8 weeks, with equal efficiency to recombinant human bone morphogenetic protein-2 (rhBMP-2). Unlike rhBMP-2, Oxy133 did not induce adipogenesis in the fusion mass and resulted in denser bone evidenced by greater bone volume/tissue volume (BV/TV) ratio and smaller trabecular separation. Findings here suggest that Oxy133 has significant potential as an osteogenic molecule with greater ease of synthesis and improved time to fusion compared to previously studied oxysterols. Small molecule osteogenic oxysterols may serve as the next generation of bone anabolic agents for therapeutic development.

Surgical management of PCL injuries: indications, techniques, and outcomes.

The ideal treatment for posterior cruciate ligament (PCL) injuries is controversial and remains an active area of orthopedic research. The indications for surgery and the ideal method of reconstruction continue to be evaluated in biomechanical and clinical studies. Recent research has provided information on the anatomy and biomechanics of the PCL, and the merits and drawbacks of the transtibial compared with the tibial inlay technique, the use of single vs double-bundle reconstruction, and different graft options for reconstruction. This review discusses important factors in the surgical treatment of PCL injuries, with attention to the most current literature on these topics.

Use of autogenous bone graft compared with RhBMP in high-risk patients: a comparison of fusion rates and time to fusion.

STUDY DESIGN: A retrospective study. OBJECTIVE: To evaluate whether recombinant human bone morphogenetic protein (rhBMP-2) can improve fusion rates and time to fusion in high-risk patients when compared with autograft in lumbar posterolateral fusion. SUMMARY OF BACKGROUND DATA: The use of rhBMP-2 in the general population for posterolateral fusion has resulted in relatively good reported outcomes; however, it is currently considered "off-label" use. Few studies, however, have determined the outcomes of rhBMP-2 when used in patients with numerous risk factors for a pseudarthrosis. METHODS: One hundred ninety-five patients were divided into 4 groups depending on fusion material and the presence/absence of fusion-related risk factors for nonunions; group A was defined as rhBMP-2 used in the presence of high-risk factors (FRRF), group B was defined as rhBMP-2 used in the absence of FRRF, group C was defined as autograft used in the presence of FRRF, and group D was defined as autograft used in the absence of FRRF. The time to fusion, fusion rate were compared between each group. RESULTS: The time to fusion was significantly faster in group B than in group D in patients with no history of smoking (P<0.05), hypertension (P<0.01), or other significant comorbidity (P<0.05). The time to complete fusion was also significantly faster in group B than in group D in patients under the age of 65 (P<0.05), patients undergoing primary surgery (P<0.05), single-level surgery (P<0.01), no smoking history (P<0.05), no diabetes mellitus (P<0.01), no hypertension (P=0.001), no osteoporosis (P<0.01), and no significant comorbidity (P<0.01). Although the fusion rate was higher in group B than in group D, with the exception of sex and single-level surgery, there were no significant differences between groups B and D. Although initial fusion mass and time to solid fusion was faster in group A than in group C, there were no significant differences between groups A and C. In addition, fusion rates were higher in group C than in group A, looking at all factors except revision surgery, but the differences were not statistically significant. CONCLUSIONS: With relative low dosage of rhBMP-2 compared with the dose used in Food and Drug Administration trial, in patients without fusion-related risk factors, rhBMP-2 may lead to acceptable fusion rates and faster fusion time when compared with autograft. Therefore, rhBMP-2 may serve as an acceptable alternative to autogenous bone graft in patients without fusion-related risk factors undergoing instrumented posterolateral lumbar fusions. When compared with patients with fusion-related risk factors, the use of rhBMP-2 was comparable with autograft but was not sufficient to overcome all aspects of the weakened osteoinductive capacity encountered in patients with these risk factors.

Bone morphogenetic protein-binding peptide reduces the inflammatory response to recombinant human bone morphogenetic protein-2 and recombinant human bone morphogenetic protein-7 in a rodent model of soft-tissue inflammation.

BACKGROUND CONTEXT: Bone morphogenetic protein (BMP)-2 and BMP-7 are used to enhance bone formation in spine surgery, but the use of these materials is associated with side effects including inflammation, especially in the soft tissues of the neck. Bone morphogenetic protein-binding peptide (BBP) binds BMP-2 and BMP-7 and imparts a "slow-release" property to collagen carrier. PURPOSE: To test the hypothesis that the addition of BBP will reduce the soft-tissue inflammation induced by the implantation of BMP-2 and BMP-7 on a collagen sponge. STUDY DESIGN/SETTING: Prospective in vivo rodent model of inflammation. METHODS: We implanted six different materials absorbed onto collagen sponges: absorbable collagen sponge (ACS) alone; BBP alone; recombinant human bone morphogenetic protein (rhBMP)-2 alone; rhBMP-2 plus BBP; rhBMP-7 alone; and rhBMP-7 plus BBP. Sponges were implanted bilaterally (subcutaneously [SC] and intramuscularly [IM]) into the backs of rats. Using magnetic resonance imaging, inflammation was assessed in terms of soft-tissue edema volume at 3 hours and at 2, 4, and 7 days. The animal subjects were killed on Day 7, and the dimensions of the inflammatory mass were measured manually in the case of SC tissue and those of the inflammatory zone were determined subsequently by microscopic examination in the case of muscle. RESULTS: Both the SC and the IM soft-tissue edema volumes in the rhBMP-2 plus BBP and the rhBMP-7 plus BBP groups were significantly lower than those observed in the rhBMP-2 alone and rhBMP-7 alone groups. The edema volume associated with BBP alone was greater than that associated with ACS alone but less than that associated with the other treatment groups. The measurements of inflammatory masses and zone yielded similar results. CONCLUSIONS: Bone morphogenetic protein-binding peptide may reduce the inflammatory response associated with the use of rhBMP-2 and rhBMP-7 in a rodent model of inflammation and in a form that has previously been shown to enhance the activity of BMPs. These preliminary studies suggest that BBP may have the potential to be used in the future to improve healing and reduce soft-tissue swelling in surgical applications of BMPs.

Effects of the bone morphogenetic protein binding protein spp24 (secreted phosphoprotein 24 kD) on the growth of human lung cancer cells.

Bone morphogenetic proteins (BMPs) and transforming growth factor-beta (TGF-ß) contribute to the growth of some skeletal metastases through autocrine stimulation. Secreted phosphoprotein 24 kDa (spp24) has been shown to bind to both BMP-2 and TGF-ß and to markedly inhibit the osteogenic properties of rhBMP-2. We hypothesized that the addition of spp24 would sequester autocrine growth factors (especially BMP-2) and reduce tumor growth in a system (A549 human non-small cell lung cancer cell line) where autocrine stimulation by BMP-2 is known to be important. A549 cells were injected into two sites (subcutaneous and intraosseus) in SCID mice with and without the co-injection of BMP-2 and spp24. Tumor growth after 8 weeks was assessed through gross examination, radiological imaging, and histological analysis. Spp24 attenuated the tumor growth enhancing effects of rhBMP-2 and reduced the tumor growth when added to tumor cells that were not treated with BMP-2. We conclude that spp24 can reduce A549 cell tumor growth in both soft tissue and intraosseus environments. We hypothesize that the mechanism for this inhibition is interruption of autocrine stimulation through the sequestration of BMP-2. Spp24 can be developed into a therapeutic agent that can be employed in clinical situations where the inhibitions of BMPs and related proteins is advantageous.

Novel oxysterols have pro-osteogenic and anti-adipogenic effects in vitro and induce spinal fusion in vivo.

Stimulation of bone formation by osteoinductive materials is of great clinical importance in spinal fusion surgery, repair of bone fractures, and in the treatment of osteoporosis. We previously reported that specific naturally occurring oxysterols including 20(S)-hydroxycholesterol (20S) induce the osteogenic differentiation of pluripotent mesenchymal cells, while inhibiting their adipogenic differentiation. Here we report the characterization of two structural analogues of 20S, Oxy34 and Oxy49, which induce the osteogenic and inhibit the adipogenic differentiation of bone marrow stromal cells (MSC) through activation of Hedgehog (Hh) signaling. Treatment of M2-10B4 MSC with Oxy34 or Oxy49 induced the expression of osteogenic differentiation markers Runx2, Osterix (Osx), alkaline phosphatase (ALP), bone sialoprotein (BSP), and osteocalcin (OCN), as well as ALP enzymatic activity and robust mineralization. Treatment with oxysterols together with PPARγ activator, troglitazone (Tro), inhibited mRNA expression for adipogenic genes PPARγ, LPL, and aP2, and inhibited the formation of adipocytes. Efficacy of Oxy34 and Oxy49 in stimulating bone formation in vivo was assessed using the posterolateral intertransverse process rat spinal fusion model. Rats receiving collagen implants with Oxy 34 or Oxy49 showed comparable osteogenic efficacy to BMP2/collagen implants as measured by radiography, MicroCT, and manual inspection. Histological analysis showed trabecular and cortical bone formation by oxysterols and rhBMP2 within the fusion mass, with robust adipogenesis in BMP2-induced bone and significantly less adipocytes in oxysterol-induced bone. These data suggest that Oxy34 and Oxy49 are effective novel osteoinductive molecules and may be suitable candidates for further development and use in orthopedic indications requiring local bone formation.

Enhancement of recombinant human BMP-7 bone formation with bmp binding peptide in a rodent femoral defect model.

Bone morphogenetic binding peptide (BBP) is an 18.5 kDa fragment of a bone matrix protein peptide. A rat femoral defect model was used to test the effect of BBP combined with recombinant human bone morphogenetic protein-7 (rhBMP-7) to induced bone healing. Two doses of BBP (500 and 1000 µg) were tested with two doses of rhBMP-7 (2 and 5 µg), and the results were compared with a positive control (10 µg rhBMP-7). Bone healing was evaluated by radiology, manual palpation, microcomputed tomography, and histology. The high dose of 10 µg of rhBMP-7 resulted in a consistent 100% bone union rate and a mature histological appearance on histology, and was used as a positive control. When 1000 µg of BBP was combined with lower doses of BMP-7 (2 µg rhBMP-7 or 5 µg rhBMP-7) significant differences were seen in radiographic scores, manual palpation, and bone volume, when compared to 2 µg rhBMP-7 or 5 µg rhBMP-7 alone. The combination of 1000 µg of BBP and 5 µg rhBMP-7 also achieved 100% fusion rate, induced a larger amount of bone formation, and yielded similar maturity of bone marrow when compared with the high dosage 10 µg rhBMP-7 group. This study demonstrated that when combined together, BBP can enhance the bone healing of rhBMP-7. Improved healing imparted by the addition of BBP may result in lesser amounts of rhBMP-7 needed to achieve union in the clinical setting.

Pharyngoesophageal diverticulum: a delayed complication of anterior cervical spine surgery.

Pharyngoesophageal diverticulum after anterior cervical spine surgery is a rarely reported but potentially life-threatening complication. A case report of pharyngoesophageal diverticulum 7 years after anterior cervical spine surgery is presented. The patient suffered from dysphagia, odynophagia, recurrent fever, weight loss, and also an impressive bulging in the neck with swallowing. After careful examination and preparation, he underwent revision surgery via an open procedure, had the implants removed, pouch excised, and esophagus reconstructed reinforced by a sternohyoid muscle flap as well as an omohyoid muscle flap. The post-operative period was uneventful, and he experienced a satisfactory recovery. At last follow up, 2.5 years post surgery, the patient remained symptom free. Upon review of the literature, only six such previous reports with seven cases were found. Diagnostic tools, possible mechanism, correlative factors and treatment are discussed. This patient was fortunate that although his symptoms developed long after the initial anterior cervical operation and the pouch grew impressively large almost perforating, he still recovered well. It again proves the necessity of long-term X-ray follow up, and also reminds the surgeons to be alert of the possibility of esophageal injury even when the esophageal symptoms are mild and occur long after the initial operation.

Challenges to bone formation in spinal fusion.

Spinal arthrodesis continues to expand in clinical indications and surgical practice. Despite a century of study, failure of bone formation or pseudarthrosis can occur in individual patients with debilitating clinical symptoms. Here we review biological and technical aspects of spinal fusion under active investigation, describe relevant biomechanics in health and disease, and identify the possibilities and limitations of translational animal models. The purpose of this article is to foster collaborative efforts with researchers who model bone hierarchy. The induction of heterotopic osteosynthesis requires a complex balance of biologic factors and operative technique to achieve successful fusion. Anatomical considerations of each spinal region including blood supply, osteology, and biomechanics predispose a fusion site to robust or insufficient bone formation. Careful preparation of the fusion site and appropriate selection of graft materials remains critical but is sometimes guided by conflicting evidence from the long-bone literature. Modern techniques of graft site preparation and instrumentation have evolved for every segment of the vertebral column. Despite validated biomechanical studies of modern instrumentation, a correlation with superior clinical outcomes is difficult to demonstrate. In many cases, adjuvant biologic therapies with allograft and synthetic cages have been used successfully to reproduce the enhancement of fusion rates observed with cancellous and tricortical autograft. Current areas of investigation comprise materials science, stem cell therapies, recombinant growth factors, scaffolds and biologic delivery systems, and minimally invasive surgical techniques to optimize the biologic response to intervention. Diverse animal models are required to approach the breadth of spinal pathology and novel therapeutics.

The effect of needle size inducing degeneration in the rat caudal disc: evaluation using radiograph, magnetic resonance imaging, histology, and immunohistochemistry.

BACKGROUND CONTEXT: The rat caudal disc has been increasingly used in studying of disc degeneration because of its simplicity, low cost, and efficiency. However, the reproducibility and standardization are essential to facilitate the investigations of biologic therapeutics at different stages of degeneration. PURPOSE: To identify the effect of different needle gauges to the degenerative response in rat caudal discs and to examine its pathogenesis by looking at the cellular and matrix changes. STUDY DESIGN: In vivo study of injury-induced rat caudal disc degeneration using needle puncture. PATIENT SAMPLE: Thirty-six Lewis rats aged 12-14 weeks. OUTCOME MEASURES: The induced degenerative discs were analyzed by plain radiograph, magnetic resonance imaging (MRI) and histological examination. Proteoglycan content was assessed by alcian blue stain. Immunohistochemistry using aggrecan, collagen II, and Sox-9 was also evaluated to investigate cell differentiation and matrix changes. METHODS: All rats were divided into three groups according to different needle gauges (18G, 20G, and 22G). Caudal discs were punctured percutaneously under image guidance. Radiographs and MRI were obtained at 2 weeks interval until 8 weeks. At each time point, three rats from each group were sacrificed for histological analysis and immunohistochemistry. RESULTS: Larger needle gauges, especially 18G, produced more deterioration of the disc when compared with smaller sizes, particularly with time. Significant differences were identified in almost all parameters compared between 18G and 22G at the 8-week time point. For the effect of time in the same needle size, the differences occurred between 2- or 4-week and 8-week time point in the 18G and 20G groups. The proteoglycan and aggrecan stain gradually decreased over time. Chondrogenic differentiation was identified within the degenerative disc by detecting Sox-9 positive cells and collagen II accumulation increased as degeneration progressed. CONCLUSIONS: The puncture-induced degenerative changes in rat caudal discs can imitate the human degenerative cascade as observed in plain radiograph, MRI, histology, and immunohistochemistry. We suggest that needle size affects the occurrence of progression of degeneration; thus, the large needle size was required to accelerate the deterioration. The size of needle and time point after injury should be considered when investigating the effect of therapeutic materials to retard degeneration or regenerate the intervertebral disc.

Biomechanics of massive rotator cuff tears: implications for treatment.

BACKGROUND: Some individuals with massive rotator cuff tears maintain active shoulder abduction, and some maintain good postoperative active range of motion despite high rates of repeat tears after repair. We devised a biomechanical rationale for these observations and measured the increases in residual muscle forces necessary to maintain active shoulder motion with rotator cuff tears of various sizes. METHODS: A custom cadaver shoulder controller utilizing position and orientation closed-loop feedback control was used. Six cadaver glenohumeral joint specimens were tested in open-chain scapular plane abduction with equivalent upper extremity weight. The shoulder controller limited superior translation of the humeral head to 3.0 mm while maintaining neutral axial rotation by automatically controlling individual rotator cuff forces. Three-dimensional position and orientation and rotator cuff and deltoid force vectors were recorded. Specimens were tested with an intact rotator cuff and with 6, 7, and 8-cm tears. RESULTS: All six specimens achieved full abduction with