Substantial cultures of Propionibacterium can be found in apparently aseptic shoulders revised three years or more after the index arthroplasty.

BACKGROUND: Revisions of apparently "aseptic" shoulder arthroplasties are not infrequently culture positive for Propionibacterium, organisms that may be introduced at the time of the index surgery when the dermal sebaceous glands are transected. This report seeks to answer the question, Do surgeons performing revision shoulder arthroplasty years after the index procedure need to be concerned about the persistence of Propionibacterium? METHODS: We reviewed the medical records of 148 revision arthroplasties performed between July 2008 and June 2013 to find those revisions performed at least 3 years after the index procedure and at which intraoperative cultures were strongly positive for Propionibacterium. RESULTS: We identified 14 cases of revision surgery performed 8 ± 4 years after the original arthroplasty for which deep cultures were strongly positive for Propionibacterium. A total of 109 specimens were obtained, 84 of which were positive. All 14 patients were male. CONCLUSION: Shoulder arthroplasties revised for the mechanical problems of loosening or stiffness can be substantially culture positive for Propionibacterium, even if the revision is performed many years after the index procedure. Therefore, even in shoulder arthroplasties revised for mechanical problems years after the index procedures, surgeons should consider submitting multiple deep specimens for specific Propionibacterium culture. In the presence of persistent Propionibacterium, surgeons should consider the need for directed surgical and medical treatment in their management of a failed arthroplasty.

Rotational stability for intercarpal fixation is enhanced by a 4-tine staple.

PURPOSE: To compare the torsional stability of 6 fixation techniques for intercarpal fixation including a 4-tine, in-line staple. METHODS: We chose the scapholunate interval as the test site for rotational stability for various constructs. We used 42 pairs of embalmed scaphoids and lunates for the comparisons and created 6 construct groups. Fixation of the scapholunate gap was performed with a 3-mm screw, 2 1.1-mm (0.045-inch) K-wires spaced 2 mm apart, or 2 1.1-mm K-wires spaced 5 mm apart. One member of each pair was fixed with either a standard 2-tine peripherally placed staple or a customized 4-tine staple. Each scapholunate construct was tested in torsion to failure on a biaxial materials testing machine. RESULTS: In all cases, the 4-tine staple significantly increased rotational stability. The 2-tine staple resulted in statistically insignificant increases in rotational stability. With central fixation alone, K-wires separated by 5 mm showed the greatest resistance to torsion, and the 3-mm screw showed the least. CONCLUSIONS: Use of an in-line, 4-tine staple provided increased rotational stability and may result in enhanced healing of intercarpal ligamentous reconstructions and arthrodeses. CLINICAL RELEVANCE: A 4-tine staple compared with a standard staple provided superior rotational stability for intercarpal fixation.

Selective estrogen receptor modulators inhibit growth and progression of premalignant lesions in a mouse model of ductal carcinoma in situ.

INTRODUCTION: Ductal carcinoma in situ (DCIS) is a noninvasive premalignant lesion and is considered a precursor to invasive carcinoma. DCIS accounts for nearly 20% of newly diagnosed breast cancer, but the lack of experimentally amenable in vivo DCIS models hinders the development of treatment strategies. Here, we demonstrate the utility of a mouse transplantation model of DCIS for chemoprevention studies using selective estrogen receptor modulators (SERMs). This model consists of a set of serially transplanted lines of genetically engineered mouse mammary intraepithelial neoplasia (MIN) outgrowth (MIN-O) tissue that have stable characteristics. We studied the ovarian-hormone-responsiveness of one of the lines with a particular focus on the effects of two related SERMs, tamoxifen and ospemifene. METHODS: The estrogen receptor (ER) status and ovarian-hormone-dependence of the mouse MIN outgrowth tissue were determined by immunohistochemistry and ovarian ablation. The effects of tamoxifen and ospemifene on the growth and tumorigenesis of MIN outgrowth were assessed at 3 and 10 weeks after transplantation. The effects on ER status, cell proliferation, and apoptosis were studied with immunohistochemistry. RESULTS: The MIN-O was ER-positive and ovarian ablation resulted in reduced MIN-O growth and tumor development. Likewise, tamoxifen and ospemifene treatments decreased the MIN growth and tumor incidence in comparison with the control (P < 0.01). Both SERMs significantly decreased cell proliferation. Between the two SERM treatment groups, there were no statistically significant differences in MIN-O size, tumor latency, or proliferation rate. In contrast, the ospemifene treatment significantly increased ER levels while tamoxifen significantly decreased them. CONCLUSION: Tamoxifen and ospemifene inhibit the growth of premalignant mammary lesions and the progression to invasive carcinoma in a transplantable mouse model of DCIS. The inhibitory effects of these two SERMs are similar except for their effects on ER modulation. These differences in ER modulation may suggest different mechanisms of action between the two related SERMs and may portend different long-term outcomes. These data demonstrate the value of this model system for preclinical testing of antiestrogen or other therapies designed to prevent or delay the malignant transformation of premalignant mammary lesions in chemoprevention.

Syngeneic mouse mammary carcinoma cell lines: two closely related cell lines with divergent metastatic behavior.

Two cell lines, Met-1(fvb2) and DB-7(fvb2), with different metastatic potential, were derived from mammary carcinomas in FVB/N-Tg(MMTV-PyVmT) and FVB/N-Tg(MMTV-PyVmT ( Y315F/Y322F )) mice, transplanted into syngeneic FVB/N hosts and characterized. The lines maintain a stable morphological and biological phenotype after multiple rounds of in vitro culture and in vivo transplantation. The Met-1(fvb2) line derived from a FVB/N-Tg(MMTV-PyVmT) tumor exhibits invasive growth and 100% metastases when transplanted into the females FVB/N mammary fat pad. The DB-7(fvb2) line derived from the FVB/N-Tg(MMTV-PyVmT ( Y315F/Y322F )) with a "double base" modification at Y315F/Y322F exhibits more rapid growth when transplanted into the mammary fat pad, but a lower rate of metastasis (17%). The Met1(fvb2) cells show high activation of AKT, while DB-7(fvb2) cells show very low levels of AKT activation. The DNA content and gene expression levels of both cell lines are stable over multiple generations. Therefore, these two cell lines provide a stable, reproducible resource for the study of metastasis modulators, AKT molecular pathway interactions, and gene target and marker discovery.

Polyomavirus middle T-induced mammary intraepithelial neoplasia outgrowths: single origin, divergent evolution, and multiple outcomes.

The development of models to investigate the pathobiology of premalignant breast lesions is a critical prerequisite for development of breast cancer prevention and early intervention strategies. Using tissue transplantation techniques, we modified the widely used polyomavirus middle T (PyV-mT) transgenic mouse model of breast cancer to study the premalignant stages of tumorigenesis. Premalignant atypical lesions were isolated from PyV-mT transgenic mice and used to generate two sets of three mammary intraepithelial neoplasia (MIN) outgrowth lines. Investigation of these six unique lines, each of which fulfills the criteria for MIN, has provided new information regarding the biology of PyV-mT-induced neoplasia. Although expression of the PyV-mT transgene was the primary initiating event for all lines, they exhibited different tumor latencies, metastatic potentials, and morphologies. Six distinguishable morphologic patterns of differentiation were identified within the premalignant outgrowths that are likely to represent several tumorigenic pathways. Further, several tumor phenotypes developed from each line and the tumors developing from the six lines had different metastatic potentials. These observations are consistent with the hypothesis that distinct pathways of PyV-mT-initiated neoplastic progression lead to different outcomes with respect to latency and metastasis. The MIN outgrowth lines share several characteristics with precursors of human breast cancer including the observation that gene expression profiles of tumors are more similar to those of the MIN outgrowth line outgrowth from which they developed than to other tumors. These lines provide an opportunity to study the full range of events occurring secondary to PyV-mT expression in the mammary gland.

Rotator cuff repair: published evidence on factors associated with repair integrity and clinical outcome.

BACKGROUND: Rotator cuff tears are common, and rotator cuff repair represents a major health care expense. While patients often benefit from rotator cuff repair, anatomic failure of the repair is not unusual. PURPOSE: To identify the published evidence on the factors associated with retears and with suboptimal clinical outcomes of rotator cuff repairs. STUDY DESIGN: Systematic review and meta-analysis of articles with evidence levels 1-4. METHODS: A total of 2383 articles on rotator cuff repairs published between 1980 and 2012 were identified. Only 108 of these articles, reporting on over 8011 shoulders, met the inclusion criteria of reporting quantitative data on both imaging and clinical outcomes after rotator cuff repair. Factors related to the patients, their shoulders, the procedures, and the results were systematically categorized and submitted for meta-analysis. RESULTS: While the number of relevant articles published per year increased dramatically over the period of the study, the clinical and anatomic results did not show improvement over this period. The weighted mean retear rate was 26.6% at a mean of 23.7 months after surgery. Retears were associated with more fatty infiltration, larger tear size, advanced age, and double-row repairs. Clinical improvement averaged 72% of the maximum possible improvement. Patient-reported outcomes were generally improved whether or not the repair restored the integrity of the rotator cuff. The inconsistent and incomplete data in the published articles limited the meta-analysis of factors affecting the outcome of rotator cuff repair. CONCLUSION: In spite of a dramatic increase in the number of publications per year, there is little evidence that the results of rotator cuff repair are improving. The information needed to guide the management of this commonly treated and costly condition is seriously deficient. To accumulate the evidence necessary to inform practice, future clinical studies on the outcome of rotator cuff repair must report important data relating to each patient's condition, the surgical technique, the outcome in terms of integrity, and the change in patient self-assessed comfort and function.

Molecular analysis of metastasis in a polyomavirus middle T mouse model: the role of osteopontin.

INTRODUCTION: In order to study metastatic disease, we employed the use of two related polyomavirus middle T transgenic mouse tumor transplant models of mammary carcinoma (termed Met and Db) that display significant differences in metastatic potential. METHODS: Through suppression subtractive hybridization coupled to the microarray, we found osteopontin (OPN) to be a highly expressed gene in the tumors of the metastatic mouse model, and a lowly expressed gene in the tumors of the lowly metastatic mouse model. We further analyzed the role of OPN in this model by examining sense and antisense constructs using in vitro and in vivo methods. RESULTS: With in vivo metastasis assays, the antisense Met cells showed no metastatic tumor formation to the lungs of recipient mice, while wild-type Met cells, with higher levels of OPN, showed significant amounts of metastasis. The Db cells showed a significantly reduced metastasis rate in the in vivo metastasis assay as compared with the Met cells. Db cells with enforced overexpression of OPN showed elevated levels of OPN but did not demonstrate an increase in the rate of metastasis compared with the wild-type Db cells. CONCLUSIONS: We conclude that OPN is an essential regulator of the metastatic phenotype seen in polyomavirus middle T-induced mammary tumors. Yet OPN expression alone is not sufficient to cause metastasis. These data suggest a link between metastasis and phosphatidylinositol-3-kinase-mediated transcriptional upregulation of OPN, but additional phosphatidylinositol-3-kinase-regulated genes may be essential in precipitating the metastasis phenotype in the polyomavirus middle T model.

Insurance status and delay in orthotic treatment in children.

OBJECTIVE: To determine if the type of health insurance is associated with a delay in children obtaining orthoses. METHODS: The medical records of 60 children who were prescribed an ankle-foot orthosis (AFO) or thoracolumbosacral orthosis (TLSO) were retrospectively reviewed. Ten children were randomly chosen with either of 3 types of insurance (government, health maintenance organizations [HMOs], and preferred provider organizations [PPOs]) with an orthosis provided by a single supplier. The time interval between prescription and insurance company authorization was recorded, as well as the interval between prescription and procurement of the orthosis. RESULTS: There were significant differences in the time from prescription to authorization of orthoses between insurance types (P = 0.001) and time from authorization until brace procurement between insurance types (P = 0.01). Children with PPO insurance received authorization for an AFO faster than children with government insurance or an HMO (P < 0.05). Children with government insurance received authorization for a TLSO significantly later than children with PPO insurance (P = 0.004) or HMO insurance (P = 0.03). The difference in time between authorization and procurement of a TLSO in children with PPO insurance (36 days) was strikingly different from that of children with government insurance (123 days) (P = 0.003). DISCUSSION: This study documents that children with government insurance face delays in obtaining orthotic treatment compared with children with PPO insurance. The delay in the procurement of the more expensive brace (TLSO is approximately 4 times the cost of an AFO) correlated to more striking delays in the government-insured population.

In vivo positron-emission tomography imaging of progression and transformation in a mouse model of mammary neoplasia.

Imaging mouse models of human cancer promises more effective analysis of tumor progression and reduction of the number of animals needed for statistical power in preclinical therapeutic intervention trials. This study utilizes positron emission tomography imaging of 2-[18F]-fluoro-deoxy-D-glucose to monitor longitudinal development of mammary intraepithelial neoplasia outgrowths in immunocompetent FVB/NJ mice. The mammary intraepithelial neoplasia outgrowth tissues mimic the progression of breast cancer from premalignant ductal carcinoma in situ to invasive carcinoma. Progression of disease is clearly evident in the positron emission tomography images, and tracer uptake correlates with histological evaluation. Furthermore, quantitative markers of disease extracted from the images can be used to track proliferation and progression in vivo over multiple time points.