ACVIM Consensus Statement on the management of status epilepticus and cluster seizures in dogs and cats.

BACKGROUND: Seizure emergencies (ie, status epilepticus [SE] and cluster seizures [CS]), are common challenging disorders with complex pathophysiology, rapidly progressive drug-resistant and self-sustaining character, and high morbidity and mortality. Current treatment approaches are characterized by considerable variations, but official guidelines are lacking. OBJECTIVES: To establish evidence-based guidelines and an agreement among board-certified specialists for the appropriate management of SE and CS in dogs and cats. ANIMALS: None. MATERIALS AND METHODS: A panel of 5 specialists was formed to assess and summarize evidence in the peer-reviewed literature with the aim to establish consensus clinical recommendations. Evidence from veterinary pharmacokinetic studies, basic research, and human medicine also was used to support the panel's recommendations, especially for the interventions where veterinary clinical evidence was lacking. RESULTS: The majority of the evidence was on the first-line management (ie, benzodiazepines and their various administration routes) in both species. Overall, there was less evidence available on the management of emergency seizure disorders in cats in contrast to dogs. Most recommendations made by the panel were supported by a combination of a moderate level of veterinary clinical evidence and pharmacokinetic data as well as studies in humans and basic research studies. CONCLUSIONS AND CLINICAL RELEVANCE: Successful management of seizure emergencies should include an early, rapid, and stage-based treatment approach consisting of interventions with moderate to preferably high ACVIM recommendations; management of complications and underlying causes related to seizure emergencies should accompany antiseizure medications.

Magnetic resonance imaging characteristics of atlanto-axial subluxation in 42 dogs: Analysis of joint cavity size, subluxation distance, and craniocervical junction anomalies.

Background: Atlanto-axial (AA) subluxation can be a complex syndrome in dogs. Accurate identification and assessment of this condition are key to providing treatment and resolution. Aim: The purpose of this retrospective study was to describe the magnetic resonance imaging (MRI) characteristics of AA subluxation and associated neurologic deficits. Methods: A multicenter review of dogs with a diagnosis of AA subluxation was conducted, evaluating signalment, neurologic grade, duration of signs, and MRI characteristics. MRI characteristics included degree of spinal cord compression and joint subluxation, integrity of odontoid ligaments, presence of a dens, spinal cord signal intensity, and presence of syringohydromyelia, hydrocephalus, and Chiari-like malformation. A control population with normal AA joints was also evaluated. MR images of 42 dogs with AA subluxation were compared to 26 age and breed-matched control dogs. Results: Affected dogs had a median age of 27 months and a median weight of 2.7 kg, and the most commonly affected breed was the Yorkshire terrier (47.5%). Spinal cord signal hyperintensity, increased AA joint size, and cross-sectional cord compression at the level of the dens and mid-body C2 were associated with AA subluxation. No associations were found between cord compression, the appearance of the dens, or cord signal intensity and neurologic grade. Affected dogs did not have a higher incidence of Chiari-like malformation, syringohydromyelia, or hydrocephalus than control dogs, and their neurologic grade was not associated with MRI findings. Lack of dens and/or odontoid ligaments was associated with larger subluxations. Conclusion: Dogs with clinical signs of AA subluxation were significantly more likely to have intramedullary hyperintensity at the level of compression ( p = 0.0004), an increased AA joint cavity size ( p = 0.0005), and increased spinal cord compression at the level of dens and mid-body C2 (p ≤ 0.05). The authors suggest an AA joint cavity size >1.4 mm and a subluxation distance >2.5 mm as cutoffs for MRI diagnosis of AA subluxation in dogs. No differences were noted between dogs with AA subluxation and control dogs regarding syringohydromyelia, hydrocephalus, and Chiari-like malformation.

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.

Multiplex analysis of cytokines in the cerebrospinal fluid of dogs after ischemic stroke reveals elevations in chemokines CXCL1 and MCP-1.

Introduction: Neuroinflammation that occurs in the brain after stroke has been shown to be important to disease pathogenesis and outcomes. The aim of this study was to evaluate a large number of pro- and anti-inflammatory cytokines in dogs with clinically-confirmed, naturally occurring stroke. Materials and methods: Fifteen dogs with a clinical diagnosis of ischemic stroke and ten healthy control dogs were included in the study. A multiplex immunoassay was utilized to evaluate cerebrospinal fluid for GM-CSF, IFN-γ, IL-2, IL-4, IL-6, IL-7, IL-8, IL-10, IL-15, IL-18, IP-10, CXCL1, MCP-1, and TNF-α. Results: Mean concentrations of CXCL1 (stroke-436 pg/ml, control-267 pg/ml, p = 0.01) and MCP-1 (stroke-196 pg/ml, control-66 pg/ml, p ≤ 0.0001) were significantly elevated in dogs with stroke when compared with control dogs. Location and type of infarct, duration of clinical signs, and use of anti-inflammatory medications were not associated with differences in cytokine concentration. Discussion: CXCL1 and MCP-1 may play a role in naturally occurring canine stroke and represent targets for future research.

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.

Tanshinone IIA-Loaded Nanoparticle and Neural Stem Cell Therapy Enhances Recovery in a Pig Ischemic Stroke Model.

Induced pluripotent stem cell-derived neural stem cells (iNSCs) are a multimodal stroke therapeutic that possess neuroprotective, regenerative, and cell replacement capabilities post-ischemia. However, long-term engraftment and efficacy of iNSCs is limited by the cytotoxic microenvironment post-stroke. Tanshinone IIA (Tan IIA) is a therapeutic that demonstrates anti-inflammatory and antioxidative effects in rodent ischemic stroke models and stroke patients. Therefore, pretreatment with Tan IIA may create a microenvironment that is more conducive to the long-term survival of iNSCs. In this study, we evaluated the potential of Tan IIA drug-loaded nanoparticles (Tan IIA-NPs) to improve iNSC engraftment and efficacy, thus potentially leading to enhanced cellular, tissue, and functional recovery in a translational pig ischemic stroke model. Twenty-two pigs underwent middle cerebral artery occlusion (MCAO) and were randomly assigned to a PBS + PBS, PBS + iNSC, or Tan IIA-NP + iNSC treatment group. Magnetic resonance imaging (MRI), modified Rankin Scale neurological evaluation, and immunohistochemistry were performed over a 12-week study period. Immunohistochemistry indicated pretreatment with Tan IIA-NPs increased iNSC survivability. Furthermore, Tan IIA-NPs increased iNSC neuronal differentiation and decreased iNSC reactive astrocyte differentiation. Tan IIA-NP + iNSC treatment enhanced endogenous neuroprotective and regenerative activities by decreasing the intracerebral cellular immune response, preserving endogenous neurons, and increasing neuroblast formation. MRI assessments revealed Tan IIA-NP + iNSC treatment reduced lesion volumes and midline shift. Tissue preservation and recovery corresponded with significant improvements in neurological recovery. This study demonstrated pretreatment with Tan IIA-NPs increased iNSC engraftment, enhanced cellular and tissue recovery, and improved neurological function in a translational pig stroke model.

Are models of plantar heel pain suitable for competitive runners? A narrative review.

Background: Plantar heel pain (PHP), or plantar fasciopathy, is a common condition in active and sedentary populations, contributing to short- and long-term reductions in quality of life. The condition's aetiology and pathophysiology are the subjects of a significant body of research. However, much of this research has been conducted with sedentary participants, and comparatively little research exists in a population of highly-trained athletes focused on performance outcomes. Models for PHP and proposed mechanisms, such as high body mass index or systemic disease, are mostly absent from an athletic population. Even less is known about the origins of pain in PHP. Pain is believed to be a complex multifactorial process and may be experienced differently by sedentary and highly active populations, particularly endurance athletes. Consequently, conservative through to surgical treatment for athletes is informed by literature for a different population, potentially hindering treatment outcomes. Aims: The aim of this review, therefore, is to summarise what is known about PHP in athletic populations and propose potential directions for future research. Methods: Embase, PubMed, and Scopus using MeSH search terms for PHP and competitive sport and common synonyms. Discussion: Two explanatory models for PHP were found. These primarily propose mechanical factors for PHP. It remains unclear how gait, body composition, and psychological factors may differ in an athletic population with and without PHP. Therefore, research in these three areas is needed to inform clinical and training interventions for this population.

Pain catastrophising, body mass index and depressive symptoms are associated with pain severity in tertiary referral orthopaedic foot/ankle patients.

INTRODUCTION: Patients with chronic foot/ankle pain are often referred for orthopaedic assessment. Psychological vulnerabilities influence pain states (including foot and ankle), therefore this study aimed to establish the prevalence and relative importance of compromised psychological health to perceived foot/ankle pain severity in people referred to an orthopaedic foot and ankle clinic with non-urgent presentations. METHODS: Patients with triaged non-urgent foot/ankle referrals to the Department of Orthopaedics at Gold Coast University Hospital were recruited over a 12-month period and completed the Manchester-Oxford Foot and Ankle Questionnaire which was the primary measure. Participants also completed questionnaires assessing their anthropometric, demographic and health characteristics (Self-Administered Comorbidity Questionnaire) as well as measures of health-related quality of life (EuroQol-5-Dimensions-5-Level Questionnaire and EQ Visual Analogue Scale) and psychological health (Center for Epidemiological Studies-Depression scale, Pain Catastrophizing Scale and Central Sensitization Inventory). Descriptive statistics were used to summarise participant characteristics and a hierarchical multiple linear regression was employed to establish the extent to which psychological variables explain additional variance in foot/ankle pain severity beyond the effects of participant characteristics (age, sex, body mass index (BMI)). RESULTS: One hundred and seventy-two adults were recruited ((64.0% female), median (IQR) age 60.9 (17.7) years and BMI 27.6 (7.5) kg/m2). Specific psychological comorbidities were prevalent including depressive symptoms (48%), central sensitisation (38%) and pain catastrophising (24%). Age, sex and BMI accounted for 11.7% of the variance in MOXFQ-index and psychological variables accounted for an additional 28.2%. Pain catastrophising was the most significant independent predictor of foot/ankle pain severity (accounting for 14.4% of variance), followed by BMI (10.7%) and depressive symptoms (2.3%). CONCLUSIONS: This study demonstrated that specific psychological comorbidities and increased BMI are common in this cohort and that these factors are associated with the symptoms for which patients are seeking orthopaedic assessment. This knowledge should prompt clinicians to routinely consider the psychosocial components of patient presentations and develop non-operative and pre-operative treatment strategies which consider these factors with the goal of improving overall patient outcomes.

Cost-Effectiveness of Interventions for Musculoskeletal Foot and Ankle Conditions: A Systematic Review.

OBJECTIVE: Musculoskeletal conditions of the foot and ankle are common, yet the cost-effectiveness of the variety of treatments available is not well defined. The aim of this systematic review was therefore to identify, appraise, and synthesize the literature pertaining to the cost-effectiveness of interventions for musculoskeletal foot and ankle conditions. METHODS: Electronic databases were searched for studies presenting economic evaluations of nonsurgical and surgical treatments for acute or chronic musculoskeletal conditions of the foot and ankle. Data on cost, incremental cost-effectiveness, and quality-adjusted life years for each intervention and comparison were extracted. Risk of bias was assessed using the Drummond checklist for economic studies (range 0-35). RESULTS: Thirty-six studies were identified reporting nonsurgical interventions (n = 10), nonsurgical versus surgical interventions (n = 14), and surgical interventions (n = 12). The most common conditions were osteoarthritis, ankle fracture, and Achilles tendon rupture. The strongest economic evaluations were for interventions managing end-stage ankle osteoarthritis, ankle sprain, ankle fracture, calcaneal fracture, and Achilles tendon rupture. Total ankle replacement and ankle arthrodesis for end-stage ankle osteoarthritis, in particular, have been demonstrated through high-quality studies to be cost-effective compared to the nonsurgical alternative. CONCLUSION: Selected interventions for musculoskeletal foot and ankle conditions dominate comparators, whereas others require thoughtful consideration as they provide better clinical improvements, but at an increased cost. Researchers should consider measuring and reporting costs alongside clinical outcome to provide context when determining the appropriateness of interventions for other foot and ankle symptoms to best inform future clinical practice guidelines.

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.

Psychological dysfunction associated with calcaneal fractures.

INTRODUCTION: The calcaneus is the most commonly fractured hindfoot bone, accounting for over 60% of all tarsal fractures. The aim of this study was to compare the mechanism of injury and psychological health status in patients presenting with calcaneal fractures to an age- and sex-matched control group with ankle fractures. PATIENTS AND METHODS: This retrospective study was undertaken within an orthopaedic unit at a tertiary hospital. An electronic medical record chart review was performed to identify eligible patients. Descriptive statistics were used to summarise the demographic and clinical characteristics of the patients. Between-group differences were analysed with the Mann-Whitney U test and Fisher's exact test for continuous and categorical variables, respectively. Multivariable binary logistic regression was used to determine the relationship between fracture type and underlying psychopathology, adjusting for mechanism of injury. RESULTS: Two-hundred and fifteen patients met the eligibility criteria for calcaneal fractures and these patients were subsequently matched to 215 ankle fracture patients. Men accounted for 154 (71.6%) of the patients in each group. Over half (51.2%) of all calcaneal fractures were due to an uncontrolled fall above one-metre, as opposed to 26.0% of ankle fractures, p < 0.001. Falling from a standing height was more common in the ankle fracture group, 37 (17.2%) versus 10 (4.7%), p < 0.001. Patients with calcaneal fractures were more likely to have a diagnosed psychological health complaint, 63 (29.3%) versus 32 (14.9%), p < 0.001. Suicidal ideation was significantly more common in the calcaneal fracture group 14 (6.5%) versus 3 (1.4%), p = 0.011. The presence of premorbid psychopathology was associated with calcaneal fracture, after adjusting for mechanism of injury (odds ratio 2.20, 95% confidence interval 1.32 to 3.65, p = 0.003). CONCLUSION: Calcaneal and ankle fractures display differences in both the mechanism of injury and the history of psychological health conditions. However, after adjusting for the mechanism of injury, diagnosed premorbid psychopathology remains twice as likely in someone with a calcaneal fracture as opposed to an ankle fracture. It may be prudent for orthopaedic surgeons to consider further investigations of psychological health when managing patients with a calcaneal fracture.

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.

Peri-ictal magnetic resonance imaging characteristics in dogs with suspected idiopathic epilepsy.

BACKGROUND: The pathophysiology of changes in magnetic resonance imaging (MRI) detected after a seizure is not fully understood. OBJECTIVE: To characterize and describe seizure-induced changes detected by MRI. ANIMALS: Eighty-one client-owned dogs diagnosed with idiopathic epilepsy. METHODS: Data collected retrospectively from medical records and included anatomical areas affected, T1-, T2-weighted and T2-FLAIR (fluid-attenuated inversion recovery) appearance, whether changes were unilateral or bilateral, symmetry, contrast enhancement, mass effect, and, gray and white matter distribution. Diffusion- and perfusion weighted maps were evaluated, if available. RESULTS: Seizure-induced changes were T2-hyperintense with no suppression of signal on FLAIR. Lesions were T1-isointense (55/81) or hypointense (26/81), local mass effect (23/81) and contrast enhancement (12/81). The majority of changes were bilateral (71/81) and symmetrical (69/71). The most common areas affected were the hippocampus (39/81) cingulate gyrus (33/81), hippocampus and piriform lobes (32/81). Distribution analysis suggested concurrence between cingulate gyrus and pulvinar thalamic nuclei, the cingulate gyrus and parahippocampal gyrus, hippocampus and piriform lobe, and, hippocampus and parahippocampal gyrus. Diffusion (DWI) characteristics were a mixed-pattern of restricted, facilitated, and normal diffusion. Perfusion (PWI) showed either hypoperfusion (6/9) or hyperperfusion (3/9). CONCLUSIONS AND CLINICAL IMPORTANCE: More areas, than previously reported, have been identified that could incur seizure-induced changes. Similar to human literature, DWI and PWI changes have been identified that could reflect the underlying metabolic and vascular changes.

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.

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.

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.

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.