How good is the orthopaedic literature?

Randomized trials constitute approximately 3% of the orthopaedic literature Concerns regarding quality of the orthopaedic literature stem from a widespread notion that the overall quality of the surgical literature is in need of improvement. Limitations in surgical research arises primarily from two pervasive issues: 1) A reliance on low levels of evidence to advance surgical knowledge, and 2) Poor reporting quality among the high level surgical evidence that is available. The scarcity of randomized trials may be largely attributable to several unique challenges which make them difficult to conduct. We present characteristics of the orthopaedic literature and address the challenges of conducting randomized trials in surgery

Treatment of CD30-Expressing Germ Cell Tumors and Sex Cord Stromal Tumors with Brentuximab Vedotin: Identification and Report of Seven Cases

BACKGROUND: Cytotoxic therapy for relapsed and refractory germ cell tumors or metastatic sex cord stromal tumors is rarely effective and is often accompanied by high adverse event rates. Expression of CD30 has been observed in testicular cancers, and patients with CD30-expressing embryonal carcinomas have worse progression-free survival and overall survival than those with CD30-negative tumors. The objective of this study (NCT01461538) was to characterize the antitumor activity of brentuximab vedotin in patients with CD30-expressing nonlymphomatous malignancies. Enrolled patients included seven patients with relapsed or refractory germ cell tumors or metastatic sex cord stromal tumors described in this case series. MATERIALS AND METHODS: Forty patients with relapsed or refractory germ cell tumors, metastatic sex cord stromal tumors, or testicular tumors were screened for CD30 expression; 14 patients had tumors that expressed CD30. Seven patients with CD30-expressing testicular cancer were enrolled in the treatment study: five patients with germ cell tumors, one patient with a Leydig cell tumor, and one patient with a Sertoli cell tumor. Patients were treated with brentuximab vedotin at initial doses of 1.8 or 2.4 mg/kg every 3 weeks. Response assessments were performed at cycles 2 and 4 and every 4 cycles thereafter while the patient was receiving treatment. RESULTS: Two of seven patients achieved an objective response, including one durable complete response and one partial response at a single time point. Both responding patients had germ cell tumors. Treatment with brentuximab vedotin was generally well tolerated. CONCLUSION: Treatment of relapsed or refractory germ cell tumors with brentuximab vedotin can induce durable responses with a manageable toxicity profile. IMPLICATIONS FOR PRACTICE: This case series of seven patients with relapsed or refractory CD30-expressing germ cell tumors (GCTs) or sex cord stromal tumors demonstrates that brentuximab vedotin has activity against GCTs and is well tolerated in heavily pretreated patients with these aggressive tumor types. One patient achieved a complete response that has been durable for almost 4 years since the discontinuation of treatment with brentuximab vedotin. Therefore, brentuximab vedotin may be a valuable option for physicians who care for this difficult-to-treat patient population

Automated Behavioral Analysis Using Instance Segmentation

Animal behavior analysis plays a crucial role in various fields, such as life science and biomedical research. However, the scarcity of available data and the high cost associated with obtaining a large number of labeled datasets pose significant challenges. In this research, we propose a novel approach that leverages instance segmentation-based transfer learning to address these issues. By capitalizing on fine-tuning the classification head of the instance segmentation network, we enable the tracking of multiple animals and facilitate behavior analysis in laboratory-recorded videos. To demonstrate the effectiveness of our method, we conducted a series of experiments, revealing that our approach achieves exceptional performance levels, comparable to human capabilities, across a diverse range of animal behavior analysis tasks. Moreover, we emphasize the practicality of our solution, as it requires only a small number of labeled images for training. To facilitate the adoption and further development of our method, we have developed an open-source implementation named Annolid (An annotation and instance segmentation-based multiple animal tracking and behavior analysis package). The codebase is publicly available on GitHub at https://github.com/cplab/annolid. This resource serves as a valuable asset for researchers and practitioners interested in advancing animal behavior analysis through state-of-the-art techniques

On the position of a heavy Higgs pole

Higher loop calculations in the Higgs sector of the standard model at the Higgs mass scale have shown that perturbation theory diverges very badly at about 1 TeV in the on-shell renormalization scheme. The prediction of the position of the Higgs pole in the complex s-plane becomes unreliable. We show that in the pole renormalization scheme this appears to have much better convergence properties, while showing good agreement with the on-shell scheme over the validity range of the latter. This suggests that the pole scheme should be preferable for phenomenological studies of heavy Higgs bosons. We discuss whether this behaviour can be the result of a certain relation between the on-shell mass and the pole mass at the nonperturbative level.Comment: replaced by the published version, 12 pages LaTex, 3 eps figures include

Primary Teratoma of the Lesser Sac: Lesser Sac Teratoma

Germ cell tumors predominantly involve the gonads but may rarely be found outside of the gonads, primarily in midline structures. We describe the case of a 27-year-old male with an asymptomatic 8 cm teratoma located within the lesser sac of his omentum. This is the fourth case of a teratoma located within the lesser sac of the omentum, which provides the opportunity to make some comparisons. Finally, we discuss some of the etiologic theories behind extragonadal germ cell tumors and how they relate to teratomas in the lesser sac

Molecular Mechanisms Controlling Bone Formation During Fracture Healing and Distraction Osteogenesis

Fracture healing and distraction osteogenesis have important applications in orthopedic, maxillofacial, and periodontal treatment. In this review, the cellular and molecular mechanisms that regulate fracture repair are contrasted with bone regeneration that occurs during distraction osteogenesis. While both processes have many common features, unique differences are observed in the temporal appearance and expression of specific molecular factors that regulate each. The relative importance of inflammatory cytokines in normal and diabetic healing, the transforming growth factor beta superfamily of bone morphogenetic mediators, and the process of angiogenesis are discussed as they relate to bone repair. A complete summary of biological activities and functions of various bioactive factors may be found at COPE (Cytokines & Cells Online Pathfinder Encyclopedia), http://www.copewithcytokines.de/cope.cgi

Loops and legs beyond perturbation theory

Within the non-perturbative 1/N expansion, we discuss numerical methods for calculating multi-loop Feynman graph needed to derive physical scattering amplitudes. We apply higher order 1/N methods to the scalar sector of the standard model, and show the existence of a mass saturation effect. The mass saturation has direct implications for future searches at the LHC and at possible muon colliders.Comment: Talk presented at the Loops and Legs in Quantum Field Theory 2000 meetin

Limit on the fermion masses in technicolor models

Recently it has been pointed out that no limits can be put on the scale of fermion mass generation $(M)$ in technicolor models, because the relation between the fermion masses $(m_f)$ and $M$ depends on the dimensionality of the interaction responsible for generating the fermion mass. Depending on this dimensionality it may happens that $m_f$ does not depend on $M$ at all. We show that exactly in this case $m_f$ may reach its largest value, which is almost saturated by the top quark mass. We make few comments on the question of how large can be a dynamically generated fermion mass.Comment: 5 pages, 1 figure, RevTeX

Diabetes Causes the Accelerated Loss of Cartilage During Fracture Repair Which Is Reversed by Insulin Treatment

Fracture healing in diabetic individuals and in animal models of diabetes is impaired. To investigate mechanisms by which diabetes may affect fracture healing we focused on the transition from cartilage to bone, a midpoint in the fracture healing process. Femoral fractures were induced in mice rendered diabetic by multiple low dose streptozotocin treatment and compared to matching normoglycemic mice. One group of diabetic animals was treated with slow release insulin to maintain normal serum glucose levels. The results indicate that there was relatively little difference in the initial formation of the fracture callus on day 10. However, on day 16 the diabetic group had significantly smaller callus, greater loss of cartilage and enhanced osteoclastogenesis that was normalized by treatment with insulin when assessed by histomorphometric analysis. Chondrocyte apoptosis was significantly higher in diabetic mice and this increase was blocked by insulin. These changes were accompanied by diabetes-increased mRNA levels of RANKL, TNF-α, and ADAMTS-4 and -5 measured by real-time PCR, which was reversed by insulin treatment. On days 16 and 22 bone formation within the callus of diabetic mice was significantly less than the normoglycemic and brought to normal levels by insulin treatment. These results suggest that a significant effect of diabetes on fracture healing is increased chondrocyte apoptosis and osteoclastogenesis that accelerates the loss of cartilage and reduces the anlage for endochondral bone formation during fracture repair. That insulin reverses these effects demonstrates that they are directly related to the diabetic condition

Chemokine Expression Is Upregulated in Chondrocytes in Diabetic Fracture Healing

Chemokines are thought to play an important role in several aspects of bone metabolism including the recruitment of leukocytes and the formation of osteoclasts. We investigated the impact of diabetes on chemokine expression in normal and diabetic fracture healing. Fracture of the femur was performed in streptozotocin-induced diabetic and matched normoglycemic control mice. Microarray analysis was carried out and chemokine mRNA levels in vivo were assessed. CCL4 were examined in fracture calluses by immunohistochemistry and the role of TNF in diabetes-enhanced expression was investigated by treatment of animals with the TNF-specific inhibitor, pegsunercept. In vitro studies were conducted with ATDC5 chondrocytes. Diabetes significantly upregulated mRNA levels of several chemokines in vivo including CCL4, CCL8, CCL6, CCL11, CCL20, CCL24, CXCL2, CXCL5 and chemokine receptors CCR5 and CXCR4. Chondrocytes were identified as a significant source of CCL4 and its expression in diabetic fractures was dependent on TNF (P \u3c 0.05). TNF-α significantly increased mRNA levels of several chemokines in vitro which were knocked down with FOXO1 siRNA (P \u3c 0.05). CCL4 expression at the mRNA and proteins levels was induced by FOXO1 over-expression and reduced by FOXO1 knockdown. The current studies point to the importance of TNF-α as a mechanism for diabetes enhanced chemokine expression by chondrocytes, which may contribute to the accelerated loss of cartilage observed in diabetic fracture healing. Moreover, in vitro results point to FOXO1 as a potentially important transcription factor in mediating this effect