Randomized feasibility study of an autologous protein solution versus corticosteroids injection for treating subacromial pain in the primary care setting - the SPiRIT trial.

Aims: The primary aim of this study was to assess the feasibility of recruiting and retaining patients to a patient-blinded randomized controlled trial comparing corticosteroid injection (CSI) to autologous protein solution (APS) injection for the treatment of subacromial shoulder pain in a community care setting. The study focused on recruitment rates and retention of participants throughout, and collected data on the interventions' safety and efficacy. Methods: Participants were recruited from two community musculoskeletal treatment centres in the UK. Patients were eligible if aged 18 years or older, and had a clinical diagnosis of subacromial impingement syndrome which the treating clinician thought was suitable for treatment with a subacromial injection. Consenting patients were randomly allocated 1:1 to a patient-blinded subacromial injection of CSI (standard care) or APS. The primary outcome measures of this study relate to rates of recruitment, retention, and compliance with intervention and follow-up to determine feasibility. Secondary outcome measures relate to the safety and efficacy of the interventions. Results: A total of 53 patients were deemed eligible, and 50 patients (94%) recruited between April 2022 and October 2022. Overall, 49 patients (98%) complied with treatment. Outcome data were collected in 100% of participants at three months and 94% at six months. There were no significant adverse events. Both groups demonstrated improvement in patient-reported outcome measures over the six-month period. Conclusion: Our study shows that it is feasible to recruit to a patient-blinded randomized controlled trial comparing APS and CSI for subacromial pain in terms of clinical outcomes and health-resource use in the UK. Safety and efficacy data are presented.

Association of Preexisting Triple Fusion and Arthroscopic Ankle Arthrodesis nonunion.

BACKGROUND: Arthroscopic ankle arthrodesis (AAA) is a successful treatment for end-stage ankle arthritis. A significant early complication of AAA is symptomatic nonunion. Published nonunion rates range from 8% to 13%. Longer term, there is concern that it predisposes to subtalar joint (STJ) fusion. To better understand these risks, we undertook a retrospective investigation of primary AAA. METHODS: All adult AAA cases conducted at our institution over a 10-year period were reviewed. A total of 284 eligible AAA cases in 271 patients were analyzed. The primary outcome measure was radiographic union. Secondary outcome measures included reoperative rate, postoperative complications and subsequent STJ fusion. Univariate and multivariate logistic regression analysis was performed to identify nonunion risk factors. RESULTS: The overall nonunion rate was 7.7%. Smoking (odds ratio [OR] 4.76 [1.67, 13.6], P = .004) and previous triple fusion (OR 40.29 [9.46, 171.62], P < .001) were independent risk factors on univariate analysis. Only prior triple fusion persisted as a major risk factor associated with nonunion on multivariate analysis (OR 18.3 [3.4, 99.7], P < .001). Seventy percent of patients with a previous triple fusion went on to develop nonunion compared to 5.5% of those without. Increasing age, obesity, surgical grade, diabetes, postoperative weightbearing plan, steroid use, and inflammatory arthropathy were not significant risk factors. The leading cause of reoperation was hardware removal (18%). There were 5 superficial (1.8%) and 4 deep (1.4%) infections. Eleven (4.2%) required subsequent STJ fusion. The "survivorship" of STJ post AAA was 98%, 85%, and 74% at 2, 5, and 9 years, respectively. CONCLUSION: As the largest study of AAA in the literature, our findings suggest prior triple fusion is a major independent risk factor for AAA nonunion. These patients should be counseled of this high risk and may benefit from alternative surgical options. LEVEL OF EVIDENCE: Level III, retrospective cohort study.

Shoulder instability in military personnel: diagnosis and outcomes of arthroscopic stabilisation.

INTRODUCTION: Shoulder instability is a common problem for military personnel due to the highly physical demands of work and training. This study assessed the pattern of glenoid labrum tears suffered by serving UK military personnel, the reliability of preoperative diagnostic methods (magnetic resonance arthrogram (MRA) vs clinical examination) and, finally, the outcomes of arthroscopic stabilisation in terms of satisfaction, pain, and return to sport and full deployment. METHODS: Retrospective demographic and clinical data were collected for all patients within our unit who underwent arthroscopic shoulder stabilisation between September 2016 and January 2019. Patients underwent clinical examination for instability and subsequent imaging with MRA. For service evaluation, patient-reported outcome measure data and occupational outcome data were gathered preoperatively and postoperatively. RESULTS: 41 military patients with shoulder instability were treated with arthroscopic stabilisation. 24.4% had an isolated anterior tear, and 41.5% had complex two-zone or pan-labral tears identified on arthroscopy. Clinical examination showed higher sensitivity, accuracy and negative predictive value for all labral tear patterns compared with MRA. Mean preoperative Oxford Shoulder Instability Score score was 18.58 (SE ±1.67) and mean postoperative score was 41.5 (SE ±1.13). 82.14% of the patients returned to full deployment during the study period and 85% had returned to sports. CONCLUSION: Complex labral tear patterns are common in military personnel with shoulder instability, and clinical examination appears to be more effective than imaging at predicting injury pattern. Patients respond well to arthroscopic stabilisation with good rates of return to work and sport, regardless of chronicity of injury.

Thermal stabilization of diverse biologics using reversible hydrogels.

Improving the thermal stability of biologics, including vaccines, is critical to reduce the economic costs and health risks associated with the cold chain. Here, we designed a versatile, safe, and easy-to-use reversible PEG-based hydrogel platform formed via dynamic covalent boronic ester cross-linking for the encapsulation, stabilization, and on-demand release of biologics. Using these reversible hydrogels, we thermally stabilized a wide range of biologics up to 65°C, including model enzymes, heat-sensitive clinical diagnostic enzymes (DNA gyrase and topoisomerase I), protein-based vaccines (H5N1 hemagglutinin), and whole viruses (adenovirus type 5). Our data support a generalized protection mechanism for the thermal stabilization of diverse biologics using direct encapsulation in reversible hydrogels. Furthermore, preliminary toxicology data suggest that the components of our hydrogel are safe for in vivo use. Our reversible hydrogel platform offers a simple material solution to mitigate the costs and risks associated with reliance on a continuous cold chain for biologic transport and storage.

Signatures of Post-Glacial Genetic Isolation and Human-Driven Migration in the Dothistroma Needle Blight Pathogen in Western Canada.

Many current tree improvement programs are incorporating assisted gene flow strategies to match reforestation efforts with future climates. This is the case for the lodgepole pine (Pinus contorta var. latifolia), the most extensively planted tree in western Canada. Knowledge of the structure and origin of pathogen populations associated with this tree would help improve the breeding effort. Recent outbreaks of the Dothistroma needle blight (DNB) pathogen Dothistroma septosporum on lodgepole pine in British Columbia and its discovery in Alberta plantations raised questions about the diversity and population structure of this pathogen in western Canada. Using genotyping-by-sequencing on 119 D. septosporum isolates from 16 natural pine populations and plantations from this area, we identified four genetic lineages, all distinct from the other DNB lineages from outside of North America. Modeling of the population history indicated that these lineages diverged between 31.4 and 7.2 thousand years ago, coinciding with the last glacial maximum and the postglacial recolonization of lodgepole pine in western North America. The lineage found in the Kispiox Valley from British Columbia, where an unprecedented DNB epidemic occurred in the 1990s, was close to demographic equilibrium and displayed a high level of haplotypic diversity. Two lineages found in Alberta and Prince George (British Columbia) showed departure from random mating and contemporary gene flow, likely resulting from pine breeding activities and material exchanges in these areas. The increased movement of planting material could have some major consequences by facilitating secondary contact between genetically isolated DNB lineages, possibly resulting in new epidemics.

Safety and efficiency of gasless laparoscopy: a systematic review protocol.

BACKGROUND: Gasless laparoscopy, developed in the early 1990s, was a means to minimize the clinical and financial challenges of pneumoperitoneum and general anaesthesia. It has been used in a variety of procedures such as in general surgery and gynecology procedures including diagnostic laparoscopy. There has been increasing evidence of the utility of gasless laparoscopy in resource limited settings where diagnostic imaging is not available. In addition, it may help save costs for hospitals. The aim of this study is to conduct a systematic review of the available evidence surrounding the safety and efficiency of gasless laparoscopy compared to conventional laparoscopy and open techniques and to analyze the benefits that gasless laparoscopy has for low resource setting hospitals. METHODS: This protocol is developed by following the Preferred Reporting Items for Systematic review and Meta-Analysis-Protocols (PRISMA-P). The PRISMA statement guidelines and flowchart will be used to conduct the study itself. MEDLINE (Ovid), Embase, Web of Science, Cochrane Central, and Global Index Medicus (WHO) will be searched and the National Institutes of Health Clinical Trials database. The articles that will be found will be pooled into Covidence article manager software where all the records will be screened for eligibility and duplicates removed. A data extraction spreadsheet will be developed based on variables of interest set a priori. Reviewers will then screen all included studies based on the eligibility criteria. The GRADE tool will be used to assess the quality of the studies and the risk of bias in all the studies will be assessed using the Cochrane Risk assessment tool. The RoB II tool will assed the risk of bias in randomized control studies and the ROBINS I will be used for the non-randomized studies. DISCUSSION: This study will be a comprehensive review on all published articles found using this search strategy on the safety and efficiency of the use of gasless laparoscopy. The systematic review outcomes will include safety and efficiency of gasless laparoscopy compared to the use of conventional laparoscopy or laparotomy. TRIAL REGISTRATION: The study has been registered in PROSPERO under registration number: CRD42017078338.

Antibiotic Prophylaxis in Adults With Open Tibial Fractures: What Is the Evidence for Duration of Administration? A Systematic Review.

Open tibial fractures are common injuries after high-energy trauma such as road traffic accidents. Infection is one of the main complications of open fractures. Broad-spectrum antibiotics have been used for prophylaxis and treatment of infection in these fractures. The duration of antibiotic prophylaxis remains controversial, especially for the different types and grades of open fractures. No complete review, to date, has been performed of published studies to demonstrate the wide variety of duration of antibiotic use in practice to prevent infection, especially in open tibial fractures. The purpose of the present study was to review the evidence in the current data regarding the duration of prophylactic antibiotic administration in open tibial fractures and to identify the optimum duration of administration of antibiotics to minimize the risk of infection in these fractures. We reviewed and evaluated all published clinical trials claiming or cited elsewhere as being authoritative regarding the duration of prophylactic antibiotic use in open tibial fracture management. A large number of studies reported antibiotic prophylaxis in open fractures; however, only 8 met the inclusion criteria set out for our review. Only 1 randomized, double-blind, prospective study examined the duration of prophylactic antibiotic administration in open tibial fractures. That study suggested a short course of antibiotics is as effective as a long course in infection prophylaxis. The results of the present review highlight the need for a rigorous randomized, double-blind, multicenter trial to establish an agreed protocol for the optimal length of prophylactic antibiotic administration in open tibial fractures.

T-LAK cell-originated protein kinase presents a novel therapeutic target in FLT3-ITD mutated acute myeloid leukemia.

Gain-of-function mutations of FLT3 (FLT3-ITD), comprises up to 30% of normal karyotype acute myeloid leukemia (AML) and is associated with an adverse prognosis. Current FLT3 kinase inhibitors have been tested extensively, but have not yet resulted in a survival benefit and novel therapies are awaited. Here we show that T-LAK cell-originated protein kinase (TOPK), a mitotic kinase highly expressed in and correlated with more aggressive phenotype in several types of cancer, is expressed in AML but not in normal CD34+ cells and that TOPK knockdown decreased cell viability and induced apoptosis. Treatment of AML cells with TOPK inhibitor (OTS514) resulted in a dose-dependent decrease in cell viability with lower IC50 in FLT3-mutated cells, including blasts obtained from patients relapsed after FLT3-inhibitor treatment. Using a MV4-11-engrafted mouse model, we found that mice treated with 7.5 mg/kg IV daily for 3 weeks survived significantly longer than vehicle treated mice (median survival 46 vs 29 days, P < 0.001). Importantly, we identified TOPK as a FLT3-ITD and CEBPA regulated kinase, and that modulating TOPK expression or activity resulted in significant decrease of FLT3 expression and CEBPA phosphorylation. Thus, targeting TOPK in FLT3-ITD AML represents a novel therapeutic approach for this adverse risk subset of AML.