Runx2, a bone-specific transcriptional regulator, is abnormally expressed in highly metastatic prostate cancer cells. Here, we identified the functional activities of Runx2 in facilitating tumor ...growth and osteolysis. Our studies show that negligible Runx2 is found in normal prostate epithelial and non-metastatic LNCaP prostate cancer cells. In the intra-tibial metastasis model, high Runx2 levels are associated with development of large tumors, increased expression of metastasis-related genes (MMP9, MMP13, VEGF, Osteopontin) and secreted bone-resorbing factors (PTHrP, IL8) promoting osteolytic disease. Runx2 siRNA treatment of PC3 cells decreased cell migration and invasion through Matrigel in vitro, and in vivo shRunx2 expression in PC3 cells blocked their ability to survive in the bone microenvironment. Mechanisms of Runx2 function were identified in co-culture studies showing that PC3 cells promote osteoclastogenesis and inhibit osteoblast activity. The clinical significance of these findings is supported by human tissue microarray studies of prostate tumors at stages of cancer progression, in which Runx2 is expressed in both adenocarcinomas and metastatic tumors. Together these findings indicate that Runx2 is a key regulator of events associated with prostate cancer metastatic bone disease.
•Cephalomeduallary (CMN) nail cut-out continues to occur at an unacceptably high rate, affecting 6.4% of the current study population.•Contrary to earlier studies involving CMN cut-out after ...treatment of geriatric hip fractures, no difference in rate of cut-out was observed between helical blade and lag screws in the current study.•Amongst risk factors for cut-out examined in the current study, fracture reduction quality was the sole variable associated with increased risk for implant cut-out.•When considering mechanisms of failure, medial perforation occurs at a significantly higher rate with helical blades than lag screws.•A lower Tip-Apex Distance may increase risk for cut-out following helical blade fixation.
Implant cut-out remains a common cause of cephalomedullary nail (CMN) failure and patient morbidity following surgical treatment of intertrochanteric femur fractures. Recent studies have suggested an increased rate of CMN cut-out with helical blades as opposed to lag screws. We compared rates of overall cut-out between helical blades and lag screws and used bivariate and multivariate analysis to determine the role of proximal fixation method among other variables on risk for cut-out. Subgroup analysis was performed on the basis of failure mechanism; superior migration (Fig. 2) versus medial perforation (Fig. 3).
Three-hundred and thirteen patient charts were retrospectively reviewed over an 8-year period; 245 patients were treated with helical blades and 68 with lag screws. Radiographs were reviewed for fracture pattern, Tip-Apex Distance (TAD), Parker’s Ratio (PR) and reduction quality. Rate of implant cut-out was compared between groups and multiple logistic regression was used to analyze the ability of several independent variables to predict implant cut-out.
Twenty cut-outs occurred; 15 with helical blades and 5 with lag screws. No difference in the rate of cut-out was observed between the two groups (p = 0.45). Poor fracture reduction was found to be a significant predictor of implant failure via bivariate and multiple logistic regression analysis (p = <0.01, OR 23.573). Helical blade fixation, fracture instability, TAD ≥ 25, and PR ≥ 0.45 were not predictive of implant cut-out during multivariate analysis. Similarly, patient smoking status and surgeon trauma fellowship training did not significantly increase the odds of implant cut-out. Failure by medial perforation occurred in 12 instances, all involving helical blades. Failure by superior migration occurred at a significantly higher rate with lag screws than helical blades (p = 0.02).
CMN cutout is likely multifactorial. A direct association between helical blade fixation and implant cut-out was not observed in our study. Amongst modifiable risk factors for implant failure, poorer fracture reduction was predictive of failure by cut-out. Subgroup analysis highlights differing modes of failure between lag screws and helical blades which warrants further investigation. Ideal TAD during helical blade fixation remains unknown.
•Iliopsoas hematoma with resultant femoral nerve palsy is a rare phenomenon for which the optimal treatment is unclear.•PubMed, Embase, and Cochrane database review yielded 122 articles containing ...174 distinct cases of the syndrome.•49% of all cases resulted in persistent motor deficit – 34% of those treated surgically and 66% of those treated conservatively.•Disparate data presentation prevented direct statistical comparison of patients treated conservatively versus surgically.•Based upon review, surgical treatment is usually reserved for larger hematomas with progressive or severe neurological symptoms.
Iliopsoas hematoma with femoral nerve palsy is a rare phenomenon with no consensus treatment algorithm. The objective of this study was to perform a systematic review of all reported cases of femoral nerve palsy secondary to iliopsoas hematoma to better elucidate it's optimal treatment.
Queries of the PubMed, Embase, and Cochrane databases were performed for reports available in English of femoral nerve palsy secondary to iliopsoas, psoas, or iliacus hematoma. 1491 articles were identified. After removal of duplicated publications and review of abstract titles via a majority reviewer consensus, 217 articles remained for consideration. Dedicated review of the remaining articles (including their reference sections) yielded 122 articles representing 174 distinct cases. Clinical data including patient age, sex, medical history, use of pharmacologic anticoagulation, sensory and motor examination at presentation and follow-up, hematoma etiology and location, time to intervention, and type of intervention were collected. Descriptive statistics were generated for each variable.
Femoral nerve palsy secondary to iliopsoas hematoma occurred at a mean age of 44.5 years old. A majority of patients (60%) were male, and a majority of hematomas (54%) occurred due to pharmacologic anticoagulation. Most hematomas (57%) were treated conservatively, and almost half (49%) – regardless of treatment modality - resulted in persistent motor deficits at final follow-up. A minority of patients treated surgically (34%) had residual motor deficit at final follow-up, while 66% of those treated medically had resultant motor deficits, although no direct statistical comparison was able to be performed.
The disparate available data on iliopsoas hematoma with femoral nerve palsy precludes the completion of a true metanalysis, and therefore any conclusions on an optimal treatment algorithm. Based on review of the literature, small to moderate hematomas are often treated conservatively, while larger hematomas with progressive neurological symptoms are usually managed with a percutaneous decompression or surgery.
IV
Interest in phages as adjunctive therapy to treat difficult infections has grown in the last decade. However, phage dosing and delivery for orthopedic infections have not been systematically ...summarized.
Following PRISMA-ScR guidelines, we conducted a SCOPING review through September 1st, 2023, of MEDLINE, Embase, Web of Science Core Collection, and Cochrane Central.
In total, 77 studies were included, of which 19 (24.7%) were in vitro studies, 17 (22.1%) were animal studies, and 41 (53.2%) were studies in humans. A total of 137 contemporary patients receiving phage therapy are described.
Direct phage delivery remains the most studied form of phage therapy, notably in prosthetic joint infections, osteomyelitis, and diabetic foot ulcers. Available evidence describing phage therapy in humans suggests favorable outcomes for orthopedic infections, though this evidence is composed largely of low-level descriptive studies. Several phage delivery devices have been described, though a lack of comparative and in-human evidence limits their therapeutic application. Limitations to the use of phage therapy for orthopedic infections that need to be overcome include a lack of understanding related to optimal dosing and phage pharmacokinetics, bacterial heterogeneity in an infection episode, and phage therapy toxicity.
•Direct delivery is the most studied form of phage therapy for orthopedic infections.•Favorable outcomes can be achieved, though higher level evidence is needed.•Phage pharmacokinetics, optimal dosing, and phage toxicity require further study.•Phage delivery devices require further comparative and in-human evidence.
Runx2, required for bone formation, is ectopically expressed in breast cancer cells. To address the mechanism by which Runx2 contributes to the osteolytic disease induced by MDA-MB-231 cells, we ...investigated the effect of Runx2 on key components of the "vicious cycle" of transforming growth factor beta (TGFbeta)-mediated tumor growth and osteolysis. We find that Runx2 directly up-regulates Indian Hedgehog (IHH) and colocalizes with Gli2, a Hedgehog signaling molecule. These events further activate parathyroid hormone-related protein (PTHrP). Furthermore, Runx2 directly regulates the TGFbeta-induced PTHrP levels. A subnuclear targeting deficient mutant Runx2, which disrupts TGFbeta-induced Runx2-Smad interactions, failed to induce IHH and downstream events. In addition, Runx2 knockdown in MDA-MB-231 inhibited IHH and PTHrP expression in the presence of TGFbeta. In vivo blockade of the Runx2-IHH pathway in MDA-MB-231 cells by Runx2 short hairpin RNA inhibition prevented the osteolytic disease. Thus, our studies define a novel role of Runx2 in up-regulating the vicious cycle of metastatic bone disease, in addition to Runx2 regulation of genes related to progression of tumor metastasis.
Acute compartment syndrome (ACS) can cause catastrophic tissue damage leading to permanent muscle and nerve loss. Acute compartment syndrome is a clinical diagnosis, with intracompartmental pressure ...(ICP) used in equivocal cases. There are no reliable diagnostic methods. The clinical evaluation is impossible to standardize, and the threshold for ICP has been known to be unreliable; thus, guidelines for diagnosis can result in overtreatment or delayed diagnosis.
To present and review the advantages and disadvantages of each diagnostic modality and identify gaps that need to be addressed in the future and to review the most used and appropriate animal and human ACS models.
We included clinical studies and animal models investigating diagnostic modalities for ACS of the extremities. A MEDLINE and Web of Science search was performed. The protocol for the study was registered on PROSPERO (CRD42017079266). We assessed the quality of the clinical studies with Newcastle-Ottawa scale and reported level of evidence for each article.
Fifty-one articles were included in this study, reporting on 38 noninvasive and 35 invasive modalities. Near-infrared spectroscopy and direct ICP measurement using a Stryker device were the most common, respectively. Cadaveric studies used saline infusions to create an ACS model. Most studies with human participants included injured patients with acquired ACS or at risk of developing ACS. In healthy human participants, tourniquets formed the most commonly used ACS model. Application of tourniquets and infusion of saline or albumin were the most used ACS models among animal studies.
This article reports on the most common as well as many new and modified diagnostic modalities, which can serve as inspiration for future investigations to develop more effective and efficient diagnostic techniques for ACS. Future studies on diagnostic modalities should include the development of tools for continuous assessment of ICP to better identify the earliest alterations suggestive of impending ACS. With the advent of such technologies, it may be possible to develop far less aggressive and more effective approaches for early detection of ACS.
Transcutaneous osseointegration for amputees Evans, Andrew R; Tetsworth, Kevin; Quinnan, Stephen ...
OTA international : the open access journal of orthopaedic trauma
7, Številka:
2 Suppl
Journal Article
Recenzirano
Odprti dostop
Transcutaneous osseointegration for amputees (TOFA) is an evolving technology that has the potential to revolutionize the interface between the amputee and their prosthesis, showing potential at many ...levels of amputation. While no amputation is without its challenges, TOFA requires a highly specialized prosthesis and a multidisciplinary team that includes specialized surgeons, physical therapists, wound care teams, and social workers who guide the amputee through surgery, postoperative rehabilitation, and the chronic wound care that goes into maintaining the prosthesis. The infrastructure required to facilitate care pathways that lead to reliable, successful outcomes are unique in each health care setting, including those in advanced health care systems such as the United States and Australia. This article details the emerging evidence supporting the use of this prosthetic interface design and many of the challenges that providers face when establishing programs to offer this type of care in the United States.
Runx2, a master regulator of osteogenesis, is abnormally expressed in advanced prostate cancer. Here, we addressed Runx2 contribution to formation of prostate cancer‐related osteolytic and ...osteoblastic bone lesions by mediating TGFβ/BMP signaling through direct interaction with Smads. Further, we examined involvement of the Runx2–Smad complex in mediating tumor growth and distal metastasis. To identify Runx2–Smad‐specific mechanisms of prostate tumor activity in bone, we generated PC3 prostate cancer cell lines expressing Runx2‐WT or one of two mutant proteins (Runx2‐HTY and Runx2‐ΔC) that each disrupt the Runx2–Smad interaction, either directly through a point mutation or by deletion of the functional C‐terminus, respectively. Intratibial tumors generated from these cells revealed that Runx2‐WT‐expressing cells resulted in predominantly osteolytic disease, whereas cells expressing mutant proteins exhibited tumors with mixed osteolytic/osteoblastic lesions. Extent of bone loss and woven bone formation was assessed by radiography and micro‐computed tomography. Bioluminescent imaging showed the presence of labeled prostate cancer cells in the lung at the latest time point examined, with Runx2‐WT group exhibiting increased incidence of tumor cells in lung. Notably, disruption of the Runx2–Smad interaction significantly reduced incidence and size of lung tumors. Altered expression of Runx2 target genes involved in invasion, growth, adhesion and metastasis supported our findings. Thus, our studies demonstrate that Runx2 in prostate cancer cells plays a significant role in intratibial prostate cancer‐related tumor growth and bone loss through mechanisms mediated by the Runx2–Smad signaling pathway. This work expands upon the potential importance of Runx2 as a therapeutic target in cancer.
What's new?
Almost 80% of patients with advanced prostate cancer (PC) develop bone metastases. In this study, the authors found that the Runx2‐Smad signaling pathway mediates the growth of PC metastases in bone, and also influences further metastasis from bone to lung. When the interaction between Runx2 and Smad was blocked, the expression of genes that affect invasion, growth, adhesion, and metastasis was altered, and tumor growth was significantly reduced. These results support Runx2 as a potential therapeutic target in prostate cancer and associated bone complications.
Purpose
Low-velocity gunshot fractures (LVGFs) are a common type of gunshot-induced trauma with the potential for complications such as infection and osteomyelitis. The effectiveness of antibiotic ...therapy in LVGFs remains uncertain, leading to ongoing debate about the appropriate treatment. In this review, we evaluate recent updates on the current understanding of antibiotic therapy in LVGFs, how previous studies have investigated the use of antibiotics in LVGFs, and the current state of institutional policies and protocols for treating LVGFs with antibiotics.
Methods
We conducted a review of PubMed, Embase, and Web of Science databases to identify studies that investigated the use of antibiotics in LVGFs after the last review in 2013. Due to the lack of quantitative clinical trial studies, we employed a narrative synthesis approach to analyze and present the findings from the included primary studies. We categorized the outcomes based on the anatomical location of the LVGFs.
Results
After evaluating 67 publications with the necessary qualifications out of 578 abstracts, 17 articles were included. The sample size of the studies ranged from 22 to 252 patients. The antibiotics used in the studies varied, and the follow-up period ranged from three months to ten years. The included studies investigated the use of antibiotics in treating LVGFs at various anatomic locations, including the humerus, forearm, hand and wrist, hip, femur, tibia, and foot and ankle.
Conclusion
Our study provides updated evidence for the use of antibiotics in LVGFs and highlights the need for further research to establish evidence-based guidelines. We also highlight the lack of institutional policies for treating LVGFs and the heterogeneity in treatments among institutions with established protocols. A single-dose antibiotic approach could be cost-effective for patients with non-operatively treated LVGFs. We suggest that a national or international registry for gunshot injuries, antibiotics, and infections could serve as a valuable resource for collecting and analyzing data related to these important healthcare issues.
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