Regional Gene Therapy Compared to Recombinant BMP-2 for the Treatment of Critical-Size Bone Defects: An In Vivo Single-Cell RNA-Sequencing Study.

regional gene therapy is a promising tissue-engineering strategy for bone regeneration: osteogenic mesenchymal stem cells (MSCs) can be genetically modified to express an osteoinductive stimulus (e.g., bone morphogenetic protein-2), seeded onto an osteoconductive scaffold, and then implanted into a bone defect to exert a therapeutic effect.

Access to cancer clinical trials for racialised older adults: an equity-focused rapid scoping review protocol.

Background: The intersection of race and older age compounds existing health disparities experienced by historically marginalised communities. Therefore, racialised older adults with cancer are more disadvantaged in their access to cancer clinical trials compared with age-matched counterparts. To determine what has already been published in this area, the rapid scoping review question are: what are the barriers, facilitators and potential solutions for enhancing access to cancer clinical trials among racialised older adults?

Methods: We will use a rapid scoping review methodology in which we follow the six-step framework of Arksey and O'Malley, including a systematic search of the literature with abstract and full-text screening to be conducted by two independent reviewers, data abstraction by one reviewer and verification by a second reviewer using an Excel data abstraction sheet.

Biodistribution of lentiviral transduced adipose-derived stem cells for "ex-vivo" regional gene therapy for bone repair.

Ex-vivo gene therapy has been shown to be an effective method for treating bone defects in pre-clinical models. As gene therapy is explored as a potential treatment option in humans, an assessment of the safety profile becomes an important next step. The purpose of this study was to evaluate the biodistribution of viral particles at the defect site and various internal organs in a rat femoral defect model after implantation of human ASCs transduced with lentivirus (LV) with two-step transcriptional activation (TSTA) of bone morphogenetic protein-2 (LV-TSTA-BMP-2).

Complication Rates and Utilization Trends of 3-Level Posterior Column Osteotomy Compared to Single-Level Pedicle Subtraction Osteotomy.

Objective: The objective of this study is to assess differences in complication profiles between 3-level posterior column osteotomy (PCO) and single-level pedicle subtraction osteotomy (PSO) as both are reported to provide similar degrees of sagittal correction.

Methods: The PearlDiver database was queried retrospectively using International Classification of Disease, 9th and 10th edition and Current Procedural Terminology codes to identify patients who underwent PCO or PSO for degenerative spine disease. Patients under age 18 or with history of spinal malignancy, infection, or trauma were excluded.

Neuroma Treatment With the Acellular Nerve Allograft Reconstruction Technique.

Treatment of a painful neuroma is a challenging problem for both the patient and the providers. Current surgical treatment options typically include excision of the neuroma and stump relation. However, with both treatment options, patients have high rates of persistent pain and rates of neuroma recurrence.

Influence of donor age and comorbidities on transduced human adipose-derived stem cell in vitro osteogenic potential.

Human adipose-derived mesenchymal stem cells (ASCs) transduced with a lentiviral vector system to express bone morphogenetic protein 2 (LV-BMP-2) have been shown to reliably heal bone defects in animal models. However, the influence of donor characteristics such as age, sex, race, and medical co-morbidities on ASC yield, growth and bone regenerative capacity, while critical to the successful clinical translation of stem cell-based therapies, are not well understood. Human ASCs isolated from the infrapatellar fat pads in 122 ASC donors were evaluated for cell growth characteristics; 44 underwent additional analyses to evaluate in vitro osteogenic potential, with and without LV-BMP-2 transduction.

Effects of cell seeding technique and cell density on BMP-2 production in transduced human mesenchymal stem cells.

Small animal models have demonstrated the efficacy of ex vivo regional gene therapy using scaffolds loaded with BMP-2-expressing mesenchymal stem cells (MSCs). Prior to clinical translation, optimization of seeding techniques of the transduced cells will be important to minimize time and resource expenditure, while maximizing cell delivery and BMP-2 production. No prior studies have investigated cell-seeding techniques in the setting of transduced cells for gene therapy applications.

Improving Lentiviral Transduction of Human Adipose-Derived Mesenchymal Stem Cells.

Lentiviral transduction of human mesenchymal stem cells (MSCs) induces long-term transgene expression and holds great promise for multiple gene therapy applications. Polybrene is the most commonly used reagent to improve viral gene transfer efficiency in laboratory research; however, it is not approved for human use and has also been shown to impair MSC proliferation and differentiation. Therefore, there is a need for optimized transduction protocols that can also be adapted to clinical settings.

Shoulder Arthroplasty in the Aging Athlete: Considerations in the Younger Patient.

Shoulder arthroplasty has become an increasingly common option for the management of glenohumeral osteoarthritis in younger, higher demand, and athletic individuals. Patients with shoulder arthritis in whom nonsurgical measures fail and who are not candidates for arthroscopic treatment may be evaluated for shoulder arthroplasty. Available options include shoulder hemiarthroplasty, with or without biologic glenoid resurfacing, total shoulder arthroplasty, and less commonly reverse total shoulder arthroplasty.

Nonarthroplasty Management of Shoulder Arthritis in the Aging Athlete: Biologics and Arthroscopy.

Glenohumeral arthritis in athletes or young and active individuals constitutes a challenging clinical problem, and multiple factors should be taken into consideration when deciding on nonsurgical or surgical treatment in this patient cohort. Selection of therapy should be based on clinical evidence, but the therapeutic strategy should align with patient expectations. Patient education on the nature and progression of shoulder osteoarthritis may facilitate the decision-making process regarding the selection of treatment.

Open Stabilization Procedures of the Shoulder in the Athlete: Indications, Techniques, and Outcomes.

Shoulder instability is a relatively common injury especially in the young athletic population and its surgical management continues to remain a controversial topic in sports medicine orthopedics. Anterior instability is the most common type encountered and is estimated to have an incidence rate of 0.08 per 1000 person-years in the general population; however, this figure is likely higher in the young athletic population.

Utilizing Google Trends to Track Online Interest in Elective Hand Surgery During the COVID-19 Pandemic.

Introduction Elective hand surgery encompasses a large volume of orthopaedic cases annually. Carpal tunnel syndrome, ganglion cysts, and trigger digits are some of the most common pathologies treated by hand surgeons. In the midst of the COVID-19 pandemic, patient's interest in elective hand surgery for these conditions is uncertain.

Managing Perioperative Pain After Anterior Cruciate Ligament (ACL) Reconstruction: Perspectives from a Sports Medicine Surgeon.

Anterior cruciate ligament reconstructions (ACLR) are a relatively common procedure in orthopedic sports medicine with an estimated 130,000 arthroscopic operations performed annually. Most procedures are carried out on an outpatient basis, and though success rates of ACLR are as high as 95%, pain remains the most common postoperative complication delaying patient discharge, and thereby increasing the costs associated with patient care. Despite the success and relative frequency of ACLR surgery, optimal and widely accepted strategies and regimens for controlling perioperative pain are not well established.

Venous Thromboembolic Prophylaxis After Total Hip and Knee Arthroplasty.

➤: The selection of an agent for prophylaxis against venous thromboembolism (VTE) is a balance between efficacy and safety. The goal is to prevent symptomatic VTE while limiting the risk of bleeding.

➤: The optimal agent for VTE prophylaxis has not been identified.

Update on injury epidemiology in rowing: our experience with female NCAA Division I athletes and a systematic review of the literature.

Objectives: (1) To report the distribution of injuries per body site and time lost from participation in female NCAA Division I rowers and (2) to present an updated summary of the existing evidence regarding the analysis of injuries per body site in rowers.

Methods: Case series: The distribution of injuries per body site in female NCAA Division I rowers and the time lost from participation were retrieved from an institutional registry. Injuries per body site were reported as number of athletes with site-specific injury per total number of injured athletes.

Hip Abductor and Peritrochanteric Space Conditions.

The hip trochanteric bursa, tendinous insertions of the gluteal muscles, and the origin vastus lateralis make up the main structures of the peritrochanteric space. Greater trochanteric pain syndrome (GTPS) refers to pain generated by one or multiple disorders of the peritrochanteric space, such as trochanteric bursitis, gluteus medius and minimus tendinopathy or tear, and disorders of the proximal iliotibial band. Patients with GTPS might present with associated intra-articular hip pathology, which requires further investigation and appropriate management.

Perceptions and attitudes toward clinical trials in adolescent and young adults with cancer: a systematic review.

Purpose: Although cancer clinical trials (CT) offer opportunities for novel treatments that may lead to improved outcomes, adolescents and young adults (AYA) are less likely to participate in these trials as compared to younger children and older adults. We aimed to identify the perceptions and attitudes toward CT in AYA that influence trial participation.

Materials And Methods: A systematic review of cancer literature was conducted that assessed perceptions and attitudes toward CT enrollment limited to AYA patients (defined as age 15-39).

A risk screening tool for ethical appraisal of evidence-generating initiatives.

Background: The boundaries between health-related research and practice have become blurred as initiatives traditionally considered to be practice (e.g., quality improvement, program evaluation) increasingly use the same methodology as research.

Cancer patient decision making related to clinical trial participation: an integrative review with implications for patients' relational autonomy.

Purpose: Oncology clinical trials are necessary for the improvement of patient care as they have the ability to confirm the efficacy and safety of novel cancer treatments and in so doing, contribute to a solid evidence base on which practitioners and patients can make informed treatment decisions. However, only 3-5 % of adult cancer patients enroll in clinical trials. Lack of participation compromises the success of clinical trials and squanders an opportunity for improving patient outcomes.

Synthetic methodology for the preparation of N-hydroxysulfamides.

A convenient synthesis of a variety of substituted N-hydroxysulfamides from chlorosulfonyl isocyanate is reported. Alkyl groups can be introduced selectively on the N-Boc nitrogen of key intermediates 1a or 1b using the Mitsunobu reaction with alcohols. Subsequently the nitrogen carrying the silyloxy group can be alkylated under traditional conditions.

SARS and hospital priority setting: a qualitative case study and evaluation.

Background: Priority setting is one of the most difficult issues facing hospitals because of funding restrictions and changing patient need. A deadly communicable disease outbreak, such as the Severe Acute Respiratory Syndrome (SARS) in Toronto in 2003, amplifies the difficulties of hospital priority setting. The purpose of this study is to describe and evaluate priority setting in a hospital in response to SARS using the ethical framework 'accountability for reasonableness'.