A programmable arthritis-specific receptor for guided articular cartilage regenerative medicine.

Objective: Investigational cell therapies have been developed as disease-modifying agents for the treatment of osteoarthritis (OA), including those that inducibly respond to inflammatory factors driving OA progression. However, dysregulated inflammatory cascades do not specifically signify the presence of OA. Here, we deploy a synthetic receptor platform that regulates cell behaviors in an arthritis-specific fashion to confine transgene expression to sites of cartilage degeneration.

Pediatric Lateral Condyle Fractures With Elbow Dislocation: Revisiting the Song Classification of the Most Severe Injuries.

Introduction: Lateral condyle fractures are the second most common pediatric elbow fracture and are at risk for malunion, nonunion or avascular necrosis. The Song or Jakob classification guides management and risk of complications. However, many lateral condyle fractures have accompanying bony or soft tissue injuries, including elbow dislocations, which are not represented in the current Song or Jakob classification systems.

Age Determination Based on Open Apex Measurement in the Developing Dentition: Comparing the Accuracy of the Belgrade Age Formula (BAF) with the European Formula on a Bosnian Children Population.

Objective: The aim was to test the Belgrade age formula based on the calculation of open apices of two permanent mandibular teeth on a Bosnian children population and compare its accuracy with European formula.

Material And Methods: We included 412 panoramic images of children (204 female and 208 male) 7 to 13 years of age. We assessed the performance of both methods (the European formula and the BAF) and compared their results in both sexes.

The Thoracolumbar Injury Classification and Severity Score Appropriately Predicts Treatment in Children Aged 10 and Under.

Study Design: Retrospective cohort study.

Objective: This study aims to assess the validity of the Thoracolumbar Injury Classification and Severity Score (TLICS) in patients ≤10 years-old.

Summary Of Background Data: TLICS is a validated measure developed to help facilitate clinical decision-making regarding thoracolumbar spinal trauma in adults.

Pharmacologic Hedgehog inhibition modulates the cytokine profile of osteolytic breast cancer cells.

The establishment and progression of bone metastatic breast cancer is supported by immunosuppressive myeloid populations that enable tumor growth by dampening the innate and adaptive immune response. Much work remains to understand how to target these tumor-myeloid interactions to improve treatment outcomes. Noncanonical Hedgehog signaling is an essential component of bone metastatic tumor progression, and prior literature suggests a potential role for Hedgehog signaling and its downstream effector Gli2 in modulating immune responses.

Rapid prototyping of perfusion cell culture devices for three-dimensional imaging of mesenchymal stem cell deposition and proliferation.

Perfusion of porous scaffolds transports cells to the surface to yield cellular constructs for 3D models of disease and for tissue engineering applications. While ceramic scaffolds mimic the structure and composition of trabecular bone, their opacity and tortuous pores limit the penetration of light into the interior. Scaffolds that are both perfusable and amenable to fluorescence microscopy are therefore needed to visualize the spatiotemporal dynamics of cells in the bone microenvironment.

Restriction of arginine induces antibiotic tolerance in Staphylococcus aureus.

Staphylococcus aureus is responsible for a substantial number of invasive infections globally each year. These infections are problematic because they are frequently recalcitrant to antibiotic treatment. Antibiotic tolerance, the ability of bacteria to persist despite normally lethal doses of antibiotics, contributes to antibiotic treatment failure in S.

Venous thromboembolism After Knee Arthroscopy: Incidence, Risk Factors, Prophylaxis, and Management.

Venous thromboembolism (VTE), comprising pulmonary embolism and deep vein thrombosis, is one of the most common complications after knee arthroscopy. Sequelae of VTE include VTE recurrence, postthrombotic syndrome, and potential for loss of limb or life. Given the increasing volume of knee arthroscopy procedures worldwide and the considerable morbidity and mortality associated with VTE, it is important to prevent, diagnose, and treat VTEs efficiently and effectively.

Bone Fragility in High Fat Diet-induced Obesity is Partially Independent of Type 2 Diabetes in Mice.

Obesity and type 2 diabetes (T2D) are risk factors for fragility fractures. It is unknown whether this elevated risk is due to a diet favoring obesity or the diabetes that often occurs with obesity. Therefore, we hypothesized that the fracture resistance of bone is lower in mice fed with a high fat diet (45% kcal; HFD) than in mice that fed on a similar, control diet (10% kcal; LFD), regardless of whether the mice developed overt T2D.

PTHrP intracrine actions divergently influence breast cancer growth through p27 and LIFR.

The role of parathyroid hormone (PTH)-related protein (PTHrP) in breast cancer remains controversial, with reports of PTHrP inhibiting or promoting primary tumor growth in preclinical studies. Here, we provide insight into these conflicting findings by assessing the role of specific biological domains of PTHrP in tumor progression through stable expression of PTHrP (-36-139aa) or truncated forms with deletion of the nuclear localization sequence (NLS) alone or in combination with the C-terminus. Although the full-length PTHrP molecule (-36-139aa) did not alter tumorigenesis, PTHrP lacking the NLS alone accelerated primary tumor growth by downregulating p27, while PTHrP lacking the NLS and C-terminus repressed tumor growth through p27 induction driven by the tumor suppressor leukemia inhibitory factor receptor (LIFR).

Sequestration and Involucrum: Understanding Bone Necrosis and Revascularization in Pediatric Orthopedics.

Sequestration, a condition where a section of bone becomes necrotic due to a loss of vascularity or thrombosis, can be a challenging complication of osteomyelitis. This review explores the pathophysiology of sequestration, highlighting the role of the periosteum in forming involucrum and creeping substitution which facilitate revascularization and bone formation. The authors also discuss the induced membrane technique, a two-stage surgical procedure for cases of failed healing of sequestration.

Navigating the Enigma of Pediatric Musculoskeletal Infections: A Race Against Time.

Musculoskeletal infection (MSKI) in children is a critical condition in pediatric orthopedics due to the potential for serious adverse outcomes, including multiorgan dysfunction syndrome, which can lead to death. The diagnosis and treatment of MSKI continue to evolve with advancements in infectious organisms, diagnostic technologies, and pharmacologic treatments. It is imperative for pediatric orthopedic surgeons and medical teams to remain up to date with the latest MSKI practices.

A programmable arthritis-specific receptor for guided articular cartilage regenerative medicine.

Objective: Investigational cell therapies have been developed as disease-modifying agents for the treatment of osteoarthritis (OA), including those that inducibly respond to inflammatory factors driving OA progression. However, dysregulated inflammatory cascades do not specifically signify the presence of OA. Here, we deploy a synthetic receptor platform that regulates cell behaviors in an arthritis-specific fashion to confine transgene expression to sites characterized by cartilage degeneration.

Epigenetic control of the vicious cycle.

Epigenetic alterations, including DNA methylation and post translational modifications to histones, drive tumorigenesis and metastatic progression. In the context of bone metastasis, epigenetic modifications in tumor cells can modulate dissemination of cancer cells to the bone, tumor progression in the bone marrow, and may be associated with patient survival rates. Bone disseminated tumor cells may enter a dormant state or stimulate osteolysis through the "vicious cycle" of bone metastasis where bone disseminated tumor cells disrupt the bone microenvironment, which fuels tumor progression.

In Vivo Assessment of Bone Quality Without X-rays.

Purpose Of Review: This review summarizes recent advances in the assessment of bone quality using non-X-ray techniques.

Recent Findings: Quantitative ultrasound (QUS) provides multiple measurements of bone characteristics based on the propagation of sound through bone, the attenuation of that sound, and different processing techniques. QUS parameters and model predictions based on backscattered signals can discriminate non-fracture from fracture cases with accuracy comparable to standard bone mineral density (BMD).

CRP Predicts the Need to Escalate Care After Initial Debridement for Musculoskeletal Infection.

Background: Musculoskeletal infections (MSKIs) are a major cause of morbidity in the pediatric population and account for nearly 1 in every 10 consultations with a pediatric orthopaedic provider at a tertiary care center. To prevent or deescalate the risk of adverse medical and musculoskeletal outcomes, timely medical intervention in the form of antibiotics and potential surgical debridement is required. While there have been numerous studies indicating the value of laboratory testing during the initial workup of a child with MSKI, few studies to date have examined the utility of longitudinal assessment of laboratory measures in the acute setting to monitor the efficacy of antibiotic therapy and/or surgical intervention.

Targeting hedgehog-driven mechanisms of drug-resistant cancers.

Due to the cellular plasticity that is inherent to cancer, the acquisition of resistance to therapy remains one of the biggest obstacles to patient care. In many patients, the surviving cancer cell subpopulation goes on to proliferate or metastasize, often as the result of dramatically altered cell signaling and transcriptional pathways. A notable example is the Hedgehog (Hh) signaling pathway, which is a driver of several cancer subtypes and aberrantly activated in a wide range of malignancies in response to therapy.

Immune checkpoint inhibitors in bone metastasis: Clinical challenges, toxicities, and mechanisms.

Immune checkpoint inhibitors (ICIs) have revolutionized the field of anti-cancer therapy over the last decade; they provide durable clinical responses against tumors by inhibiting immune checkpoint proteins that canonically regulate the T cell-mediated immune response. Despite their success in many primary tumors and soft tissue metastases, ICIs function poorly in patients with bone metastases, and these patients do not have the same survival benefit as patients with the same primary tumor type (e.g.

Head and Neck Necrotizing Fasciitis: Abbreviated SOFA Score Associated With Death and Infection Spread.

Objective: Describe features unique to head and neck (H&N) necrotizing fasciitis (NF) compared to other anatomic regions and specify a prognostic score associated with death and descending necrotizing mediastinitis (DNM).

Study Design: Retrospective cohort.

Setting: Tertiary care, level 1 trauma center.

Maintaining the balance: the critical role of plasmin activity in orthopedic surgery injury response.

The musculoskeletal system plays vital roles in the body, facilitating movement, protecting vital structures, and regulating hematopoiesis and mineral metabolism. Injuries to this system are common and can cause chronic pain, loss of range of motion, and disability. The acute phase response (APR) is a complex process necessary for surviving and repairing injured musculoskeletal tissue.

Toward the use of MRI measurements of bound and pore water in fracture risk assessment.

The current clinical assessment of fracture risk lacks information about the inherent quality of a person's bone tissue. Working toward an imaging-based approach to quantify both a bone tissue quality marker (tissue hydration as water bound to the matrix) and a bone microstructure marker (porosity as water in pores), we hypothesized that the concentrations of bound water (C) are lower and concentrations of pore water (C) are higher in patients with osteoporosis (OP) than in age- and sex-matched adults without the disease. Using recent developments in ultrashort echo time (UTE) magnetic resonance imaging (MRI), maps of C and C were acquired from the uninjured distal third radius (Study 1) of 20 patients who experienced a fragility fracture of the distal radius (Fx) and 20 healthy controls (Non-Fx) and from the tibia mid-diaphysis (Study 2) of 30 women with clinical OP (low T-scores) and 15 women without OP (normal T-scores).

Re-Evaluating the Role of PTHrP in Breast Cancer.

Parathyroid-hormone-related protein (PTHrP) is a protein with a long history of association with bone metastatic cancers. The paracrine signaling of PTHrP through the parathyroid hormone receptor (PTHR1) facilitates tumor-induced bone destruction, and PTHrP is known as the primary driver of humoral hypercalcemia of malignancy. In addition to paracrine signaling, PTHrP is capable of intracrine signaling independent of PTHR1 binding, which is essential for cytokine-like functions in normal physiological conditions in a variety of tissue types.