Glioma with cribriform plate involvement in 6 dogs.

Distinct patterns of local infiltration are a common feature of canine oligodendroglioma and astrocytoma, and typically involve the surrounding neuroparenchyma, ventricles, or leptomeninges. Infiltration of adjacent extraneural sites is rare and has not been well documented in veterinary medicine. Here we describe 6 canine gliomas with cribriform plate involvement (compression or infiltration) and caudal nasal invasion confirmed by neuroimaging, autopsy, and/or histology. All affected dogs were adults (9-12-y-old), and 3 were brachycephalic. Clinical signs were associated with the brain tumor, with no respiratory signs reported. Magnetic resonance imaging in 2 patients revealed a rostral intraparenchymal telencephalic mass with extension into the cribriform plate. All dogs were euthanized. Gross changes consisted of poorly demarcated, white or pale-yellow, soft, and, in oligodendrogliomas, gelatinous, intraparenchymal masses that expanded the rostral portions of the telencephalon and adhered firmly to the ethmoid bone and cribriform plate. Gliomas were classified as high-grade oligodendrogliomas (4 cases) and high-grade astrocytomas (2 cases) based on histology and immunohistochemistry for OLIG2 and GFAP. In all cases, there was evidence of cribriform plate invasion and, in one case, additional invasion of the caudal nasal cavity.

Tanshinone IIA-loaded nanoparticles and neural stem cell combination therapy improves gut homeostasis and recovery in a pig ischemic stroke model.

Impaired gut homeostasis is associated with stroke often presenting with leaky gut syndrome and increased gut, brain, and systemic inflammation that further exacerbates brain damage. We previously reported that intracisternal administration of Tanshinone IIA-loaded nanoparticles (Tan IIA-NPs) and transplantation of induced pluripotent stem cell-derived neural stem cells (iNSCs) led to enhanced neuroprotective and regenerative activity and improved recovery in a pig stroke model. We hypothesized that Tan IIA-NP + iNSC combination therapy-mediated stroke recovery may also have an impact on gut inflammation and integrity in the stroke pigs. Ischemic stroke was induced, and male Yucatan pigs received PBS + PBS (Control, n = 6) or Tan IIA-NP + iNSC (Treatment, n = 6) treatment. The Tan IIA-NP + iNSC treatment reduced expression of jejunal TNF-α, TNF-α receptor1, and phosphorylated IkBα while increasing the expression of jejunal occludin, claudin1, and ZO-1 at 12 weeks post-treatment (PT). Treated pigs had higher fecal short-chain fatty acid (SCFAs) levels than their counterparts throughout the study period, and fecal SCFAs levels were negatively correlated with jejunal inflammation. Interestingly, fecal SCFAs levels were also negatively correlated with brain lesion volume and midline shift at 12 weeks PT. Collectively, the anti-inflammatory and neuroregenerative treatment resulted in increased SCFAs levels, tight junction protein expression, and decreased inflammation in the gut.

"I'd never have that operation again" - a mixed-methods study on how patients react to adverse outcomes following foot and ankle surgery.

BACKGROUND: Adverse outcomes arising from foot and ankle surgery, including lack of pain relief, increased disability and perioperative complications are infrequent but inevitable. This mixed-methods study aims to explore the impact of adverse outcomes on patients following nonemergent foot and ankle surgery. METHODS: Patients who underwent foot and ankle surgery over a two-year period were invited to participate in this study if they reported an adverse outcome. Qualitative assessment consisted of individual semi-structured interviews, designed to explore the decision they made to have surgery and the impact of the outcome after surgery. Quantitative assessment was performed using questionnaires on demographics, current analgesia, foot pain, health-related quality of life, psychological health, and regret. RESULTS: Twelve participants (eight women) consented for inclusion in this study. Current foot pain was high in 10 participants, five met the criteria for central sensitisation syndrome and two had clinically significant pain catastrophising. Most participants regretted their decision to have surgery. The three major themes identified were expectations, communication, and alternatives. CONCLUSIONS: Self-reported adverse outcomes following foot and ankle surgery were prevalent and participants in this study consistently complained of persistent pain. Regret was common and reasons cited for their adverse outcomes centred around the feelings of inadequate communication and failure to meet expectations.

A Systematic Review of Randomized Controlled Trials in Anterior Cruciate Ligament Reconstruction: Standard Techniques Are Comparable (299 Trials With 25,816 Patients).

PURPOSE: To provide an overview of all published randomized controlled trials (RCTs) in anterior cruciate ligament reconstruction (ACLR) summarizing the available evidence. METHODS: Following PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines, we searched the Cochrane FIGCentral Register of Controlled Trials, Ovid MEDLINE, and Embase for RCTs of ACLR from their inception to August 26, 2020. Outcome measure was whether RCTs reported statistically significant findings. RCTs were then classified according to their intervention groups in a narrative synthesis of the evidence. RESULTS: In total, 299 RCTs met the inclusion criteria and were included with a total number of 25,186 patients. Only 30 RCTs (10%) reported significant differences between the intervention and the control groups. These included 101 RCTs on grafts, 20 RCTs on tunnel placements, 48 RCTs on graft fixation, 42 RCTs on single-bundle compared with double-bundle reconstructions, 11 RCTs on additional procedures, 11 RCTs on graft tensioning, 5 RCTs on timing of surgery, 25 RCTs on technical variations from standard techniques, 6 RCTs on ACL repair, 5 RCTs on navigation, 16 RCTs on perioperative management, and 9 RCTs on other aspects of ACLR. Only 14 RCTs (4.7%) reported outcomes beyond 10 years with greater allograft failures compared with autografts, high incidence of osteoarthritic changes in reconstructed knees (22%-100%), with no significant differences in outcomes between bioabsorbable or metal screws for graft fixation, patellar versus hamstrings or single- versus double-bundle reconstructions. CONCLUSIONS: The evidence indicates that a standard arthroscopic single- or double-bundle ACLR with hamstrings/patella autografts, transportal technique, and fixation techniques familiar to the surgeon leads to comparable results. This evidence offers surgeons the flexibility to use standard and cost-effective techniques and achieve comparable outcomes. LEVEL OF EVIDENCE: Level II; systematic review of Level I-II randomized controlled trials.

Intracisternal administration of tanshinone IIA-loaded nanoparticles leads to reduced tissue injury and functional deficits in a porcine model of ischemic stroke.

BACKGROUND: The absolute number of new stroke patients is annually increasing and there still remains only a few Food and Drug Administration (FDA) approved treatments with significant limitations available to patients. Tanshinone IIA (Tan IIA) is a promising potential therapeutic for ischemic stroke that has shown success in pre-clinical rodent studies but lead to inconsistent efficacy results in human patients. The physical properties of Tan-IIA, including short half-life and low solubility, suggests that Poly (lactic-co-glycolic acid) (PLGA) nanoparticle-assisted delivery may lead to improve bioavailability and therapeutic efficacy. The objective of this study was to develop Tan IIA-loaded nanoparticles (Tan IIA-NPs) and to evaluate their therapeutic effects on cerebral pathological changes and consequent motor function deficits in a pig ischemic stroke model. RESULTS: Tan IIA-NP treated neural stem cells showed a reduction in SOD activity in in vitro assays demonstrating antioxidative effects. Ischemic stroke pigs treated with Tan IIA-NPs showed reduced hemispheric swelling when compared to vehicle only treated pigs (7.85 ± 1.41 vs. 16.83 ± 0.62%), consequent midline shift (MLS) (1.72 ± 0.07 vs. 2.91 ± 0.36 mm), and ischemic lesion volumes (9.54 ± 5.06 vs. 12.01 ± 0.17 cm3) when compared to vehicle-only treated pigs. Treatment also lead to lower reductions in diffusivity (-37.30 ± 3.67 vs. -46.33 ± 0.73%) and white matter integrity (-19.66 ± 5.58 vs. -30.11 ± 1.19%) as well as reduced hemorrhage (0.85 ± 0.15 vs 2.91 ± 0.84 cm3) 24 h post-ischemic stroke. In addition, Tan IIA-NPs led to a reduced percentage of circulating band neutrophils at 12 (7.75 ± 1.93 vs. 14.00 ± 1.73%) and 24 (4.25 ± 0.48 vs 5.75 ± 0.85%) hours post-stroke suggesting a mitigated inflammatory response. Moreover, spatiotemporal gait deficits including cadence, cycle time, step time, swing percent of cycle, stride length, and changes in relative mean pressure were less severe post-stroke in Tan IIA-NP treated pigs relative to control pigs. CONCLUSION: The findings of this proof of concept study strongly suggest that administration of Tan IIA-NPs in the acute phase post-stroke mitigates neural injury likely through limiting free radical formation, thus leading to less severe gait deficits in a translational pig ischemic stroke model. With stroke as one of the leading causes of functional disability in the United States, and gait deficits being a major component, these promising results suggest that acute Tan IIA-NP administration may improve functional outcomes and the quality of life of many future stroke patients.

A Bibliometric Analysis of 4 Major Foot and Ankle Surgery Journals.

Research publication is a central to the scientific process and comprehensive bibliometric analysis is a leading way to better understand trends within research. Currently, there are limited bibliometric analyses of literature pertaining to foot and ankle surgery. This study aims to quantify the volume of research and investigate what may affect publication and citation. Journals associated with the 3 major orthopedic foot and ankle societies (Foot & Ankle International[FAI], Foot and Ankle Surgery, and The Foot) and one podiatric college (Journal of Foot and Ankle Surgery®) were evaluated from January 2009 to December 2018 using Scopus (Elsevier, Amsterdam, the Netherlands). Descriptive statistics were used to summarize article characteristics and regression modeling was used to determine factors associated with a country's current and future productivity and an article's citation rate. A total of 4994 articles were published over the 10-year period, with the largest contributor of publications being the United States of America (USA), who produced 2096 (41.8%) publications. Regression analysis found no association between a country's productivity and gross domestic product or population. There was no significant relationship between a country's baseline publication rate and future publication rate. The variables significantly associated with an increased citation count were; the number of years since publication, the number of authors, publication in FAI and if the article was a review. To our knowledge this is the largest bibliometric analysis of foot and ankle publications. The majority of research is being produced by the USA, but there are numerous complex factors associated with citation and publication rates. Further research is required to fully assess these factors and characterize the state of foot and ankle surgery research.

Safety and interim survival data after intracranial administration of M032, a genetically engineered oncolytic HSV-1 expressing IL-12, in pet dogs with sporadic gliomas.

OBJECTIVE: The diagnosis of glioma remains disheartening in the clinical realm. While a multitude of studies and trials have shown promise, improvements in overall survival have been disappointing. Modeling these tumors in the laboratory setting has become increasingly challenging, given their complex in situ behavior and interactions for therapeutic evasion. Dogs, particularly brachycephalic breeds, are known to spontaneously develop gliomas that resemble human gliomas both clinically and pathophysiologically, making canines with sporadic tumors promising candidates for study. Typically, survival among these dogs is approximately 2 months with palliation alone. METHODS: The authors have completed the first stage of a unique phase I dose-escalating canine clinical trial in which the safety and tolerability of M032, a nonneurovirulent oncolytic herpes simplex virus-1 vector genetically engineered to express interleukin-12, are being studied in pet dogs with gliomas undergoing maximum safe tumor resection and inoculation of the cavity with the viral infusate. RESULTS: Twenty-five canine patients were enrolled between January 2018 and August 2020. One patient was electively withdrawn from the trial by its owner, and 3 did not receive the virus. For the 21 dogs that remained, 13 had high-grade gliomas, 5 had low-grade gliomas, and 3 were undetermined. According to histopathological analysis, 62% of the tumors were oligodendrogliomas. At the time of this report, the median overall survival from the date of treatment was 151 days (± 78 days). No significant adverse events attributable to M032 or dose-limiting toxicities have been observed to date. CONCLUSIONS: In this largest study of oncolytic viral therapy for canine brain tumors to date, treatment with M032 did not cause harm and the combination of surgery and oncolytic viral therapy may have contributed to prolonged survival in pet dogs with spontaneous gliomas. Forthcoming in-depth radiographic, immunohistochemical, and genetic analyses will afford a more advanced understanding of how this treatment impacts these tumors and the immune system. Our goal is to utilize these findings bitranslationally to inform human studies and refine therapies that will improve outcomes in both humans and pet dogs with gliomas.

Overview of randomised controlled trials in hallux valgus surgery (2,184 patients).

BACKGROUND: The aim of this study is to provide an overview of randomised controlled trials (RCTs) in hallux valgus correction surgery summarising the available high-quality evidence. METHODS: Following PRISMA guidelines, we searched the Cochrane Central Register of Controlled Trials, Ovid MEDLINE (1946 to 1 February 2020) and Embase (1980 to 1 February 2020). We excluded non-randomised trials, systematic reviews and case-series. We also excluded trials of MTPJ arthrodesis. Trials that met our inclusion criteria were assessed by two authors using a binary outcome measure of whether they reported statistically significant findings. These were then classified according to intervention groups. RESULTS: 32 RCTs met the inclusion criteria and were included. The total number of patients in those trials was 2,184. Only 4 RCTs (12.5%) reported significant differences between the intervention and the control groups. The remaining trials evaluated scarf or chevron osteotomies in 18 RCTs, and 10 RCTs compared other osteotomies or technical aspects of hallux valgus surgery using functional and radiological outcome measures with none reporting significant differences. CONCLUSION: Evidence from RCTs of hallux valgus surgery suggest that scarf and chevron osteotomies are the most popular techniques and lead to similar clinical outcomes.

Treatment of hallux valgus by Scarf osteotomy - rates and reasons for recurrence and rates of avascular necrosis: A systematic review.

BACKGROUND: We reviewed the rates of and reasons for hallux valgus (HV) recurrence and the rates of avascular necrosis following Scarf osteotomy. METHODS: We searched the Cochrane Library, PubMed, and Embase databases for studies reporting operative management of HV using Scarf osteotomy. The primary endpoints were reasons for and rates of HV recurrence. The secondary endpoint was the rate of avascular necrosis. RESULTS: We included 15 studies with 946 operations for HV. Seven studies reported no recurrence, six reported recurrence rates of 3.6-11.3%, one reported a recurrence rate of 30%, and one reported a recurrence rate of 78%. Thirteen studies (678 feet) reported other complications from Scarf osteotomy without avascular necrosis. CONCLUSIONS: Although HV recurrence is not uncommon following Scarf osteotomy, patient-related factors, surgical competence, and longer follow-up are more likely to be associated with recurrence. Avascular necrosis is an infrequent complication in HV patients treated using Scarf osteotomy.

Dynamic Changes in the Gut Microbiome at the Acute Stage of Ischemic Stroke in a Pig Model.

Stroke is a major cause of death and long-term disability affecting seven million adults in the United States each year. Recently, it has been demonstrated that neurological diseases, associated pathology, and susceptibility changes correlated with changes in the gut microbiota. However, changes in the microbial community in stroke has not been well characterized. The acute stage of stroke is a critical period for assessing injury severity, therapeutic intervention, and clinical prognosis. We investigated the changes in the gut microbiota composition and diversity using a middle cerebral artery (MCA) occlusion ischemic stroke pig model. Ischemic stroke was induced by cauterization of the MCA in pigs. Blood samples were collected prestroke and 4 h, 12 h, 1 day, and 5 days poststroke to evaluate circulating proinflammatory cytokines. Fecal samples were collected prestroke and 1, 3, and 5 days poststroke to assess gut microbiome changes. Results showed elevated systemic inflammation with increased plasma levels of tumor necrosis factor alpha at 4 h and interleukin-6 at 12 h poststroke, relative to prestroke. Microbial diversity and evenness were reduced at 1 day poststroke compared to prestroke. Microbial diversity at 3 days poststroke was negatively correlated with lesion volume. Moreover, beta-diversity analysis revealed trending overall differences over time, with the most significant changes in microbial patterns observed between prestroke and 3 days poststroke. Abundance of the Proteobacteria was significantly increased, while Firmicutes decreased at 3 days poststroke, compared to prestroke populations. Abundance of the lactic acid bacteria Lactobacillus was reduced at 3 days poststroke. By day 5, the microbial pattern returned to similar values as prestroke, suggesting the plasticity of gut microbiome in an acute period of stroke in a pig model. These findings provide a basis for characterizing gut microbial changes during the acute stage of stroke, which can be used to assess stroke pathology and the potential development of therapeutic targets.

The One Health Consortium: Design of a Phase I Clinical Trial to Evaluate M032, a Genetically Engineered HSV-1 Expressing IL-12, in Combination With a Checkpoint Inhibitor in Canine Patients With Sporadic High Grade Gliomas.

As the most common and deadly of primary brain tumors, malignant gliomas have earned their place within one of the most multifaceted and heavily-funded realms of medical research. Numerous avenues of pre-clinical investigation continue to provide valuable insight, but modeling the complex evolution and behavior of these tumors within a host under simulated circumstances may pose challenges to extrapolation of data. Remarkably, certain breeds of pet dogs spontaneously and sporadically develop high grade gliomas that follow similar incidence, treatment, and outcome patterns as their human glioma counterparts. The most malignant of these tumors have been refractory to limited treatment options despite aggressive treatment; outcomes are dismal with median survivals of just over 1 year in humans and 2 months in dogs. Novel treatments are greatly needed and combination therapies appear to hold promise. This clinical protocol, a dose-escalating phase I study in dogs with sporadic malignant glioma, represents a first in comparative oncology and combination immunotherapy. The trial will evaluate M032, an Interleukin-12 expressing Herpes Simplex virus, alone and combined with a checkpoint inhibitor, Indoximod. Extensive pre-clinical work has demonstrated safety of intracranial M032 administration in mice and non-human primates. M032 is currently being tested in humans with high-grade malignant gliomas. Thus, in a novel fashion, both canine and human trials will proceed concurrently allowing a direct "head-to-head" comparison of safety and efficacy. We expect this viral oncolytic therapy to be as safe as it is in human patients and M032 to (a) infect and kill glioma cells, producing a virus and tumor cell antigen-rich debris field; (b) provide an adjuvant effect due to liberation of viral DNA, which is rich in unmethylated CpG sequences that "toggle" TLR-9 receptors; and (c) express IL-12 locally, stimulating induction of TH1 lymphocytes. The resultant immune-mediated anti-viral responses should, through cross-epitope spreading, translate into a strong response to tumor antigens. The ability to compare human and dog responses in real time affords the most stringent test of suitability of the dog as an informative model of human brain tumors. Subsequent studies will allow canine trials to properly inform the design of human trials.

Overview of Randomized Controlled Trials in Primary Total Hip Arthroplasty (34,020 Patients): What Have We Learnt?

AIM: To provide an overview of randomized controlled trials (RCTs) in primary total hip arthroplasty summarizing the available high-quality evidence. MATERIALS AND METHODS: Following Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines (PRISMA), we searched the Cochrane Central Register of Controlled Trials (2020, Issue 1), Ovid MEDLINE, and Embase. We excluded nonrandomized trials, trials on neck of femur fractures or revision surgery, systematic reviews, and meta-analyses. Trials that met our inclusion criteria were assessed using a binary outcome measure of whether they reported statistically significant findings. These were then classified according to the intervention groups (surgical approach, fixation, and component design use, among others). RESULTS: Three hundred twelve RCTs met the inclusion criteria and were included. The total number of patients in those 312 RCTs was 34,020. Sixty-one RCTs (19.5%) reported significant differences between the intervention and the control groups. The trials were grouped into surgical approach 72, fixation 7, cement 16, femoral stem 46, head sizes 5, cup design 18, polyethylene 25, bearing surfaces 30, metal-on-metal 30, resurfacing 20, navigation 15, robotics 3, surgical technique 12, and closure/drains/postoperative care 13 RCTs. DISCUSSION: The evidence reviewed indicates that for the vast majority of patients, a standard conventional total hip arthroplasty with a surgical approach familiar to the surgeon using standard well-established components and highly cross-linked polyethylene leads to satisfactory clinical outcomes. This evidence also offers arthroplasty surgeons the flexibility to use the standard and cost-effective techniques and achieve comparable outcomes.

Poliomyelomalacia in three dogs that underwent hemilaminectomy for intervertebral disk herniation.

CASE DESCRIPTION: 3 dogs were examined because of a sudden onset of signs of pain (1 dog) or paraparesis (2 dogs). CLINICAL FINDINGS: Neurologic findings consisted of myelopathy affecting the lumbar intumescence (1 dog) and T3-L3 myelopathy (2 dogs). In all dogs, MRI revealed spinal cord compression caused by L3-4 disk herniation. All dogs underwent routine surgical decompression of the intervertebral disk herniation. During MRI and decompressive surgery, physiologic variables were monitored. Immediately after surgery, all dogs were paraplegic with pelvic limb neurologic dysfunction consistent with myelopathy affecting the L4 through caudal spinal cord segments. TREATMENT AND OUTCOME: Within 24 hours after surgery, repeated MRI in all dogs revealed hyperintensity in the spinal cord gray matter of the lumbar intumescence on T2-weighted images. In the absence of neurologic improvement, dogs were euthanized at 3, 91, and 34 days after surgery. Postmortem microscopic examination of each dog's spinal cord at the lumbar intumescence revealed necrosis of the gray matter with relative white matter preservation suggestive of an ischemic injury. CLINICAL RELEVANCE: Dramatic neurologic deterioration following decompressive surgery for intervertebral disk herniation in dogs may be associated with the development of poliomyelomalacia secondary to ischemia. In these 3 dogs, ischemia developed despite probable maintenance of normal spinal cord blood flow and perfusion during anesthesia. To exclude other causes, such as compression or hemorrhage, MRI was repeated and revealed hyperintensity of the spinal cord gray matter on T2-weighted images, which microscopically corresponded with ischemic neurons and neuronal loss.

Overview of Randomized Controlled Trials in Total Knee Arthroplasty (47,675 Patients): What Have We Learnt?

BACKGROUND: The aim of this study is to provide an overview of randomized controlled trials (RCTs) in primary total knee arthroplasty summarizing the available high-quality evidence. METHODS: Following PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines, we searched the Cochrane Central Register of Controlled Trials (CENTRAL, 2019, Issue 3), Ovid MEDLINE, and Embase. We excluded nonrandomized trials, trials on unicompartmental knee arthroplasty or revision surgery, systematic reviews, and meta-analyses. Trials that met our inclusion criteria were assessed using a binary outcome measure of whether they reported statistically significant findings. These were then classified according to the intervention groups (surgical approach, tourniquet use, design, etc.). RESULTS: Four hundred and three RCTs met the inclusion criteria and were included. The total number of patients in those 403 RCTs was 47,675. Only 33 RCTs (8.2%) reported significant differences between the intervention and the control groups. The trials were grouped into surgical approach 34, tourniquet 31, minimally invasive surgery 13, patient specific instrumentation 30, knee design 37, fixation 27, mobile bearing 47, navigation 50, polyethylene 19, technique 27, patella resurfacing 26, drain 19, closure 16, and others 27 RCTs. CONCLUSION: For the vast majority of patients, a standard conventional total knee arthroplasty with a surgical approach familiar to the surgeon using standard well-established components, with or without tourniquet, without surgical drain leads to satisfactory long-term clinical outcomes.

Overview of randomised controlled trials in orthopaedic research: search for significant findings.

BACKGROUND: The majority of recent orthopaedics randomised controlled trials (RCTs) have been non-inferiority trials with no significant clinical or statistical differences between treatment groups. The aim of this study was to evaluate randomised trials for significant findings in the orthopaedic literature based on the main elective procedures undertaken across different subspecialties. METHODS: We evaluated the following procedures: anterior cervical discectomy and fusion (ACDF), subacromial decompression (SAD), carpal tunnel decompression (CTD), total hip replacement (THR), anterior cruciate ligament reconstruction (ACLR), total knee replacement (TKR) and hallux valgus correction (HVC). Following PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines, we searched the Cochrane Central Register of Controlled Trials (CENTRAL, 2018, Issue 1), Ovid MEDLINE (1946 to 12 January 2018) and Embase (1980 to 12 January 2018). Trials that met our inclusion criteria were assessed using a binary outcome measure of whether they reported statistically significant findings. RESULTS: We included 1078 RCTs across seven most commonly performed elective procedures. Of those, only 16% (172/1078) reported significant findings [ACDF 26/77 (33.8%); SAD 2/22 (9%); CTD 11/72 (15.3%); THR 52/281 (18.5%); ACLR 21/239 (8.8%); TKR 55/357 (15.4%); HVC 5/30 (16.7%)]. The number of RCTs per year of publication has increased dramatically particularly since early 2000s-with over 100 RCTs of those seven procedures published in 2017 alone. CONCLUSIONS: This is the first study to undertake a comprehensive review of orthopaedic RCTs in elective practice. The number of RCTs in orthopaedic research is steadily increasing. However, only 16% of trials reports significant differences between interventions. CLINICAL RELEVANCE: For trials comparing different surgical techniques, this evidence provides treating surgeons with the flexibility to utilise available resources and infrastructure to deliver patients care without compromising clinical outcomes. Further, for trials comparing different treatment modalities, this study helps to inform the shared decision-making process when counselling patients on the effectiveness of surgical interventions.

Utility of weight-bearing radiographs compared to computed tomography scan for the diagnosis of subtle Lisfranc injuries in the emergency setting.

OBJECTIVE: The goal of the present study was to compare the diagnostic yield of weight-bearing radiographs with non-weight-bearing computed tomography (CT) scan for subtle Lisfranc (LF) injuries in the ED. METHODS: Retrospective analysis of patients presenting with a suspected LF injury over a 2 year period from 2016 to 2017 who had both weight-bearing bilateral foot radiographs and CT scan. Information extracted included patient demographics, radiographic findings of metatarsal fractures, fleck sign and measurements of diastasis between the medial cuneiform and second metatarsal expressed as a ratio of the uninjured side, clinical findings and treatment modality. Radiologist reports were recorded as either positive, negative or equivocal for a LF injury. RESULTS: A total of 117 patients were included with a mean age of 38 years and 54% (n = 63) women. When initial weight-bearing radiographs were positive, 54% of subsequent CT scans were reported as either equivocal or negative. Of the patients who had a negative or equivocal weight-bearing radiograph, only 12% had a positive CT scan. The mean diastasis ratio in patients undergoing surgery was 1.53 (95% confidence interval 1.41-1.65) compared to 1.11 (95% confidence interval 1.07-1.16) for patients with injuries not requiring operative intervention (P < 0.001). There was a statistically significant correlation between a positive weight-bearing radiograph and surgical treatment (R = 0.339, P < 0.001), and between diastasis measurements and surgical treatment (R = 0.576, P < 0.001). CONCLUSIONS: CT provides limited benefit in the diagnosis and initial management of suspected subtle LF injuries in the ED. We advocate for the use of bilateral weight-bearing radiographs as a first-line investigation.

Convection-enhanced delivery of cetuximab conjugated iron-oxide nanoparticles for treatment of spontaneous canine intracranial gliomas.

Cetuximab conjugated iron-oxide nanoparticles (cetuximab-IONPs) have shown both in-vitro and in-vivo anti-tumor efficacy against gliomas. The purpose of this pilot study was to evaluate the safety and potential efficacy of cetuximab-IONPs for treatment of spontaneously occurring intracranial gliomas in canines after convection-enhanced delivery (CED). The use of CED allowed for direct infusion of the cetuximab-IONPs both intratumorally and peritumorally avoiding the blood brain barrier (BBB) and limiting systemic effects. A total of eight dogs participated in the study and only two developed mild post-operative complications, which resolved with medical therapy. All canines underwent a single CED treatment of the cetuximab-IONPs over 3 days and did not receive any further adjuvant treatments. Volumetric analysis showed a median reduction in tumor size of 54.9% by MRI at 1-month (4-6 weeks) follow-up. Five dogs were euthanized due to recurrence of neurological signs other than seizures, two due to recurrent seizures, and one dog died in his sleep. Median survival time after surgery was 248 days (mean 367 days).

Induced Pluripotent Stem Cell-Derived Neural Stem Cell Therapy Enhances Recovery in an Ischemic Stroke Pig Model.

Induced pluripotent stem cell-derived neural stem cells (iNSCs) have significant potential as an autologous, multifunctional cell therapy for stroke, which is the primary cause of long term disability in the United States and the second leading cause of death worldwide. Here we show that iNSC transplantation improves recovery through neuroprotective, regenerative, and cell replacement mechanisms in a novel ischemic pig stroke model. Longitudinal multiparametric magnetic resonance imaging (MRI) following iNSC therapy demonstrated reduced changes in white matter integrity, cerebral blood perfusion, and brain metabolism in the infarcted tissue. The observed tissue level recovery strongly correlated with decreased immune response, enhanced neuronal protection, and increased neurogenesis. iNSCs differentiated into neurons and oligodendrocytes with indication of long term integration. The robust recovery response to iNSC therapy in a translational pig stroke model with increased predictive potential strongly supports that iNSCs may be the critically needed therapeutic for human stroke patients.