Publications by authors named "Simon R Platt"

107 Publications

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

IBRO Neurosci Rep 2021 Jun 5;10:18-30. Epub 2021 Jan 5.

Regenerative Bioscience Center, University of Georgia, Athens, GA 30602, United States.

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 cm) 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 cm) 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.
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http://dx.doi.org/10.1016/j.ibneur.2020.11.003DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8019951PMC
June 2021

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

J Vet Intern Med 2021 Mar 9;35(2):1008-1017. Epub 2021 Feb 9.

Department of Veterinary Science, Small Animal Teaching Hospital, University of Liverpool, Cheshire, United Kingdom.

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.
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http://dx.doi.org/10.1111/jvim.16058DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7995424PMC
March 2021

Magnetic Resonance Imaging and Gait Analysis Indicate Similar Outcomes Between Yucatan and Landrace Porcine Ischemic Stroke Models.

Front Neurol 2020 21;11:594954. Epub 2021 Jan 21.

Regenerative Bioscience Center, University of Georgia, Athens, GA, United States.

The Stroke Therapy Academic Industry Roundtable (STAIR) has recommended that novel therapeutics be tested in a large animal model with similar anatomy and physiology to humans. The pig is an attractive model due to similarities in brain size, organization, and composition relative to humans. However, multiple pig breeds have been used to study ischemic stroke with potentially differing cerebral anatomy, architecture and, consequently, ischemic stroke pathologies. The objective of this study was to characterize brain anatomy and assess spatiotemporal gait parameters in Yucatan (YC) and Landrace (LR) pigs pre- and post-stroke using magnetic resonance imaging (MRI) and gait analysis, respectively. Ischemic stroke was induced via permanent middle cerebral artery occlusion (MCAO). MRI was performed pre-stroke and 1-day post-stroke. Structural and diffusion-tensor sequences were performed at both timepoints and analyzed for cerebral characteristics, lesion diffusivity, and white matter changes. Spatiotemporal and relative pressure gait measurements were collected pre- and 2-days post-stroke to characterize and compare acute functional deficits. The results from this study demonstrated that YC and LR pigs exhibit differences in gross brain anatomy and gait patterns pre-stroke with MRI and gait analysis showing statistical differences in the majority of parameters. However, stroke pathologies in YC and LR pigs were highly comparable post-stroke for most evaluated MRI parameters, including lesion volume and diffusivity, hemisphere swelling, ventricle compression, caudal transtentorial and foramen magnum herniation, showing no statistical difference between the breeds. In addition, post-stroke changes in velocity, cycle time, swing percent, cadence, and mean hoof pressure showed no statistical difference between the breeds. These results indicate significant differences between pig breeds in brain size, anatomy, and motor function pre-stroke, yet both demonstrate comparable brain pathophysiology and motor outcomes post-stroke. The conclusions of this study suggest pigs of these different breeds generally show a similar ischemic stroke response and findings can be compared across porcine stroke studies that use different breeds.
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http://dx.doi.org/10.3389/fneur.2020.594954DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7859633PMC
January 2021

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

J Foot Ankle Surg 2021 Jan 19. Epub 2021 Jan 19.

Department of Orthopaedics, Gold Coast Hospital and Health Service, Southport, Australia.

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.
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http://dx.doi.org/10.1053/j.jfas.2020.11.005DOI Listing
January 2021

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.

Neurosurg Focus 2021 02;50(2):E5

Departments of1Neurosurgery.

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.
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http://dx.doi.org/10.3171/2020.11.FOCUS20844DOI Listing
February 2021

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

Front Neurosci 2020 3;14:587986. Epub 2020 Dec 3.

Department of Foods and Nutrition, College of Family and Consumer Sciences, University of Georgia, Athens, GA, United States.

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 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.
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http://dx.doi.org/10.3389/fnins.2020.587986DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7744295PMC
December 2020

Cost-effectiveness of interventions for musculoskeletal foot and ankle conditions: a systematic review.

Arthritis Care Res (Hoboken) 2020 Nov 17. Epub 2020 Nov 17.

IMPACT in Health, Allied Health & Human Performance, University of South Australia, Adelaide, South Australia, 5000, Australia.

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 synthesise 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 non-surgical 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 non-surgical interventions (n=10), non-surgical 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 non-surgical 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 complaints to best inform future clinical practice guidelines.
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http://dx.doi.org/10.1002/acr.24514DOI Listing
November 2020

Response to Letter to the Editor on: "Overview of Randomized Controlled Trials in Total Knee Arthroplasty (47,675 Patients): What Have We Learnt?"

J Arthroplasty 2020 12;35(12):3785

Holland Orthopaedic & Arthritic Centre, Sunnybrook Health Sciences, University of Toronto, Toronto, Canada.

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http://dx.doi.org/10.1016/j.arth.2020.08.054DOI Listing
December 2020

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.

Front Surg 2020 28;7:59. Epub 2020 Aug 28.

Department of Neurosurgery, University of Alabama at Birmingham, Birmingham, AL, United States.

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.
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http://dx.doi.org/10.3389/fsurg.2020.00059DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7484881PMC
August 2020

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

Foot Ankle Surg 2020 Aug 27. Epub 2020 Aug 27.

Department of Musculoskeletal Services - Surgical, Anaesthetics and Procedural Services (SaPS), Gold Coast University Hospital, Gold Coast Health, 1 Hospital Boulevard, Southport, Queensland 4215, Australia.

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.
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http://dx.doi.org/10.1016/j.fas.2020.08.009DOI Listing
August 2020

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

J Am Acad Orthop Surg Glob Res Rev 2020 08;4(8):e2000120

From the Centre for Hip Surgery (Mr. Matar, Dr. Board, and Mr. Porter), Wrightington Hospital, Appley Bridge, Wigan; and the Department of Orthopaedic Surgery (Mr. Platt), Gold Coast University Hospital, Southport, Australia.

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.
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http://dx.doi.org/10.5435/JAAOSGlobal-D-20-00120DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7417146PMC
August 2020

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

J Am Vet Med Assoc 2020 Aug;257(4):397-405

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.
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http://dx.doi.org/10.2460/javma.257.4.397DOI Listing
August 2020

Imaging Ischemic and Hemorrhagic Disease of the Brain in Dogs.

Front Vet Sci 2020 27;7:279. Epub 2020 May 27.

Department of Small Animal Medicine and Surgery, University of Georgia, Athens, GA, United States.

Strokes, both ischemic and hemorrhagic, are the most common underlying cause of acute, non-progressive encephalopathy in dogs. In effect, substantial information detailing the underlying causes and predisposing factors, affected vessels, imaging features, and outcomes based on location and extent of injury is available. The features of canine strokes on both computed tomography (CT) and magnetic resonance imaging (MRI) have been described in numerous studies. This summary article serves as a compilation of these various descriptions. Drawing from the established and emerging stroke evaluation sequences used in the investigation of strokes in humans, this summary describes all theoretically available sequences. Particular detail is given to logistics of image acquisition, description of imaging findings, and each sequence's advantages and disadvantages. As the imaging features of both forms of strokes are highly representative of the underlying pathophysiologic stages in the hours to months following stroke onset, the descriptions of strokes at various stages are also discussed. It is unlikely that canine strokes can be diagnosed within the same rapid time frame as human strokes, and therefore the opportunity for thrombolytic intervention in ischemic strokes is unattainable. However, a thorough understanding of the appearance of strokes at various stages can aid the clinician when presented with a patient that has developed a stroke in the days or weeks prior to evaluation. Additionally, investigation into new imaging techniques may increase the sensitivity and specificity of stroke diagnosis, as well as provide new ways to monitor strokes over time.
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http://dx.doi.org/10.3389/fvets.2020.00279DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7266937PMC
May 2020

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

Foot Ankle Surg 2020 May 22. Epub 2020 May 22.

Department of Orthopaedic Surgery, Gold Coast University Hospital, Hospital Blvd, Southport, Australia; Associate Professor, Griffth Univerity, QLD, Australia; Honorary Adjunct Associate Professor, Bond University, QLD, Australia. Electronic address:

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.
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http://dx.doi.org/10.1016/j.fas.2020.04.013DOI Listing
May 2020

Characterization of tissue and functional deficits in a clinically translational pig model of acute ischemic stroke.

Brain Res 2020 06 16;1736:146778. Epub 2020 Mar 16.

Regenerative Bioscience Center, University of Georgia, Athens, GA, United States; Neuroscience Program, Biomedical and Health Sciences Institute, University of Georgia, Athens, GA, United States; Department of Animal and Dairy Science, College of Agricultural and Environmental Sciences, University of Georgia, Athens, GA, United States. Electronic address:

The acute stroke phase is a critical time frame used to evaluate stroke severity, therapeutic options, and prognosis while also serving as a major tool for the development of diagnostics. To further understand stroke pathophysiology and to enhance the development of treatments, our group developed a translational pig ischemic stroke model. In this study, the evolution of acute ischemic tissue damage, immune responses, and functional deficits were further characterized. Stroke was induced by middle cerebral artery occlusion in Landrace pigs. At 24 h post-stroke, magnetic resonance imaging revealed a decrease in ipsilateral diffusivity, an increase in hemispheric swelling resulting in notable midline shift, and intracerebral hemorrhage. Stroke negatively impacted white matter integrity with decreased fractional anisotropy values in the internal capsule. Like patients, pigs showed a reduction in circulating lymphocytes and a surge in neutrophils and band cells. Functional responses corresponded with structural changes through reductions in open field exploration and impairments in spatiotemporal gait parameters. Characterization of acute ischemic stroke in pigs provided important insights into tissue and functional-level assessments that could be used to identify potential biomarkers and improve preclinical testing of novel therapeutics.
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http://dx.doi.org/10.1016/j.brainres.2020.146778DOI Listing
June 2020

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

J Arthroplasty 2020 06 30;35(6):1729-1736.e1. Epub 2020 Jan 30.

Holland Orthopaedic & Arthritic Centre, Sunnybrook Health Sciences, University of Toronto, Toronto, ON, Canada.

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.
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http://dx.doi.org/10.1016/j.arth.2020.01.065DOI Listing
June 2020

Traumatic Brain Injury Results in Dynamic Brain Structure Changes Leading to Acute and Chronic Motor Function Deficits in a Pediatric Piglet Model.

J Neurotrauma 2019 10 17;36(20):2930-2942. Epub 2019 Jun 17.

Regenerative Bioscience Center, University of Georgia, Athens, Georgia.

Traumatic brain injury (TBI) is a leading cause of death and disability in children. Pediatric TBI patients often suffer from crippling cognitive, emotional, and motor function deficits that have negative lifelong effects. The objective of this study was to longitudinally assess TBI pathophysiology using multi-parametric magnetic resonance imaging (MRI), gait analysis, and histological approaches in a pediatric piglet model. TBI was produced by controlled cortical impact in Landrace piglets. MRI data, including from proton magnetic resonance spectroscopy (MRS), were collected 24 hours and 12 weeks post-TBI, and gait analysis was performed at multiple time-points over 12 weeks post-TBI. A subset of animals was sacrificed 24 hours, 1 week, 4 weeks, and 12 weeks post-TBI for histological analysis. MRI results demonstrated that TBI led to a significant brain lesion and midline shift as well as microscopic tissue damage with altered brain diffusivity, decreased white matter integrity, and reduced cerebral blood flow. MRS showed a range of neurochemical changes after TBI. Histological analysis revealed neuronal loss, astrogliosis/astrocytosis, and microglia activation. Further, gait analysis showed transient impairments in cadence, cycle time, % stance, step length, and stride length, as well as long-term impairments in weight distribution after TBI. Taken together, this study illustrates the distinct time course of TBI pathoanatomic and functional responses up to 12 weeks post-TBI in a piglet TBI model. The study of TBI injury and recovery mechanisms, as well as the testing of therapeutics in this translational model, are likely to be more predictive of human responses and clinical outcomes compared to traditional small animal models.
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http://dx.doi.org/10.1089/neu.2018.6303DOI Listing
October 2019

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

Eur J Orthop Surg Traumatol 2019 Aug 8;29(6):1163-1168. Epub 2019 Apr 8.

Department of Orthopaedic Surgery, Gold Coast University Hospital, Hospital Blvd, Southport, Australia.

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.
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http://dx.doi.org/10.1007/s00590-019-02436-0DOI Listing
August 2019

Pathology in Practice.

J Am Vet Med Assoc 2019 Mar;254(6):685-688

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http://dx.doi.org/10.2460/javma.254.6.685DOI Listing
March 2019

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

Emerg Med Australas 2019 10 19;31(5):741-744. Epub 2019 Feb 19.

Department of Orthopaedic Surgery, Gold Coast Hospital and Health Service, Gold Coast, Queensland, Australia.

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.
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http://dx.doi.org/10.1111/1742-6723.13237DOI Listing
October 2019

Scaled traumatic brain injury results in unique metabolomic signatures between gray matter, white matter, and serum in a piglet model.

PLoS One 2018 31;13(10):e0206481. Epub 2018 Oct 31.

Regenerative Bioscience Center, University of Georgia, Athens, GA, United States of America.

Traumatic brain injury (TBI) is a leading cause of death and long-term disability in the United States. The heterogeneity of the disease coupled with the lack of comprehensive, standardized scales to adequately characterize multiple types of TBI remain to be major challenges facing effective therapeutic development. A systems level approach to TBI diagnosis through the use of metabolomics could lead to a better understanding of cellular changes post-TBI and potential therapeutic targets. In the current study, we utilize a GC-MS untargeted metabolomics approach to demonstrate altered metabolism in response to TBI in a translational pig model, which possesses many neuroanatomical and pathophysiologic similarities to humans. TBI was produced by controlled cortical impact (CCI) in Landrace piglets with impact velocity and depth of depression set to 2m/s;6mm, 4m/s;6mm, 4m/s;12mm, or 4m/s;15mm resulting in graded neural injury. Serum samples were collected pre-TBI, 24 hours post-TBI, and 7 days post-TBI. Partial least squares discriminant analysis (PLS-DA) revealed that each impact parameter uniquely influenced the metabolomic profile after TBI, and gray and white matter responds differently to TBI on the biochemical level with evidence of white matter displaying greater metabolic change. Furthermore, pathway analysis revealed unique metabolic signatures that were dependent on injury severity and brain tissue type. Metabolomic signatures were also detected in serum samples which potentially captures both time after injury and injury severity. These findings provide a platform for the development of a more accurate TBI classification scale based unique metabolomic signatures.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0206481PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6209298PMC
April 2019

Controlled Cortical Impact Severity Results in Graded Cellular, Tissue, and Functional Responses in a Piglet Traumatic Brain Injury Model.

J Neurotrauma 2019 01 21;36(1):61-73. Epub 2018 Aug 21.

1 Regenerative Bioscience Center, College of Veterinary Medicine, University of Georgia, Athens, Georgia.

A number of pre-clinical rodent models have been developed in an effort to recapitulate injury mechanisms and identify potential therapeutics for traumatic brain injury (TBI), which is a major cause of death and long-term disability in the United States. The lack of restorative treatments for TBI, however, has led to considerable criticism of current pre-clinical therapeutic development strategies-namely, the translatability of widely used rodent models to human patients. The use of large animal models, such as the pig, with more brain anatomy and physiology comparable to humans may enhance the translational capacity of current pre-clinical animal models. The objective of this study was to develop and characterize a graded piglet TBI model with quantitative pathological features at the cellular, tissue, and functional level that become more prominent with increasing TBI severity. A graded TBI was produced by controlled cortical impact (CCI) in "toddler-aged" Landrace piglets by increasing impact velocity and/or depth of depression to 2 m/sec; 6 mm; 4 m/sec; 6 mm; 4 m/sec; 12 mm; or 4 m/sec; 15 mm, producing a range of neural injury responses that corresponded to injury severity. Quantitative gait analysis was performed pre-TBI and one, three, and seven days post-TBI, and piglets were sacrificed seven days post-TBI. Increasing impact parameters correlated to increases in lesion size with piglets that sustained a 6 mm depth of depression exhibiting significantly smaller lesions than piglets that sustained a depth of depression of 12 mm or 15 mm. Similarly, the extent of neuronal loss, astrogliosis/astrocytosis, and white matter damage became more prominent as CCI parameters were increased. These cellular and tissue-level changes correlated with motor function deficits including swing/stance time, stride velocity, and two- versus three-limb support. The piglet TBI model described here could serve as a translational platform for studying TBI sequelae across injury severities and identifying novel therapeutics.
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http://dx.doi.org/10.1089/neu.2017.5551DOI Listing
January 2019

Human iNPC therapy leads to improvement in functional neurologic outcomes in a pig ischemic stroke model.

Brain Behav 2018 05 18;8(5):e00972. Epub 2018 Apr 18.

Regenerative Bioscience Center University of Georgia Athens GA USA.

Introduction: Stroke is the leading cause of disability in the United States but current therapies are limited with no regenerative potential. Previous translational failures have highlighted the need for large animal models of ischemic stroke and for improved assessments of functional outcomes. The aims of this study were first, to create a post-stroke functional outcome assessment scale in a porcine model of middle cerebral artery occlusion (MCAO) and second, to use this scale to determine the effect of human-induced-pluripotent-cell-derived neural progenitor cells (iNPCs) on functional outcome in this large animal stroke model.

Materials And Methods: Eight 6-month-old Landrace mix pigs underwent permanent MCAO. Five days following MCAO, pigs received intraparenchymal injections of either iNPCs or PBS. A post-stroke assessment scale was developed to measure functional outcome. Evaluations were performed at least 1-3 days prior to MCAO and repeated 1 day, 3 days, and 5 days post-stroke as well as 1 day, 3 days, 1 week, 2 weeks, 4 weeks, 6 weeks, 9 weeks, and 12 weeks post-injection. Comparisons of scores between animals receiving iNPCs or PBS only were compared using a two-way ANOVA and a Tukey's post-hoc test.

Results: The developed scale was able to consistently determine differences between healthy and stroked pigs at all time points. iNPC-treated pigs showed a significantly faster recovery in their overall scores relative to PBS-only treated pigs with the parameters of appetite and body posture exhibiting the most improvement in the iNPC-treated group.

Conclusions: We developed a robust and repeatable functional assessment tool that can reliably detect stroke and recovery, while also showing for the first time that iNPC therapy leads to functional recovery in a translational pig ischemic stroke model. These promising results suggest that iNPCs may 1 day serve as a first in class cell therapeutic for ischemic stroke.
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http://dx.doi.org/10.1002/brb3.972DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5943801PMC
May 2018

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

J Neurooncol 2018 May 19;137(3):653-663. Epub 2018 Jan 19.

Brain Tumor Nanotechnology Laboratory, Department of Neurosurgery, Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, 1470 Madison Avenue, New York, NY, 10029, USA.

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).
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http://dx.doi.org/10.1007/s11060-018-2764-1DOI Listing
May 2018

Pharmacokinetic evaluation of novel midazolam gel formulations following buccal administration to healthy dogs.

Am J Vet Res 2018 Jan;79(1):73-82

OBJECTIVE To determine the physiochemical properties and pharmacokinetics of 3 midazolam gel formulations following buccal administration to dogs. ANIMALS 5 healthy adult hounds. PROCEDURES In phase 1 of a 2-phase study, 2 gel formulations were developed that contained 1% midazolam in a poloxamer 407 (P1) or hydroxypropyl methylcellulose (H1) base and underwent rheological and in vitro release analyses. Each formulation was buccally administered to 5 dogs such that 0.3 mg of midazolam/kg was delivered. Each dog also received midazolam hydrochloride (0.3 mg/kg, IV). There was a 3-day interval between treatments. Blood samples were collected immediately before and at predetermined times for 8 hours after drug administration for determination of plasma midazolam concentration and pharmacokinetic analysis. During phase 2, a gel containing 2% midazolam in a hydroxypropyl methylcellulose base (H2) was developed on the basis of phase 1 results. That gel was buccally administered such that midazolam doses of 0.3 and 0.6 mg/kg were delivered. Each dog also received midazolam (0.3 mg/kg, IV). All posttreatment procedures were the same as those for phase 1. RESULTS The H1 and H2 formulations had lower viscosity, greater bioavailability, and peak plasma midazolam concentrations that were approximately 2-fold as high, compared with those for the P1 formulation. The mean peak plasma midazolam concentration for the H2 formulation was 187.0 and 106.3 ng/mL when the midazolam dose administered was 0.6 and 0.3 mg/kg, respectively. CONCLUSIONS AND CLINICAL RELEVANCE Results indicated that buccal administration of gel formulations might be a viable alternative for midazolam administration to dogs.
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http://dx.doi.org/10.2460/ajvr.79.1.73DOI Listing
January 2018

Post-operative surgical site infection in a dog.

Can Vet J 2017 Sep;58(9):936-940

Department of Small Animal Medicine and Surgery (Kent, Boozer, Platt), Athens Veterinary Diagnostic Laboratory, Department of Infectious Disease, and Department of Population Health (Sanchez), College of Veterinary Medicine, University of Georgia, Athens, Georgia 30602, USA; Section of Neurology/Neurosurgery, Red Bank Veterinary Hospital, Tinton Falls, New Jersey 07724, USA (Glass); Department of Clinical Sciences, Cummings School of Veterinary Medicine, Tufts University, North Grafton, Massachusetts, USA (Freeman).

Following decompressive surgery for degenerative lumbosacral stenosis, a 6-year-old German shepherd dog developed a subcutaneous infection at the surgical site and discospondylitis at the lumbosacral intervertebral disc. subsp. serotype Dublin was recovered from the surgical site. of a different serovar was isolated from a sample of the raw meat-based diet that the owner fed the dog.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5556475PMC
September 2017

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

Sci Rep 2017 08 30;7(1):10075. Epub 2017 Aug 30.

Regenerative Bioscience Center, University of Georgia, Athens, GA, 30602, USA.

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.
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http://dx.doi.org/10.1038/s41598-017-10406-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5577218PMC
August 2017

Evaluation of magnetic resonance imaging for the differentiation of inflammatory, neoplastic, and vascular intradural spinal cord diseases in the dog.

Vet Radiol Ultrasound 2017 Jul 18;58(4):444-453. Epub 2017 Apr 18.

The Department of Production Animal Studies, University of Pretoria, Pretoria, South Africa.

Magnetic resonance imaging (MRI) is a common test for dogs with suspected intradural spinal cord lesions, however studies on diagnostic performance for this test are lacking. Objectives of this multi-institutional, retrospective, case-control study were to estimate sensitivity and specificity of MRI for (1) distinguishing between histopathologically confirmed intradural spinal cord disease versus degenerative myelopathy in dogs, (2) categorizing intradural spinal cord diseases as neoplastic, inflammatory, or vascular; and (3) determining tumor type within the etiologic category of neoplasia. Additional aims were to (1) determine whether knowledge of clinical data affects sensitivity and specificity of MRI diagnoses; and (2) report interrater agreement for MRI classification of intradural spinal lesions. Cases were recruited from participating hospital databases over a 7-year period. Three reviewers independently evaluated each MRI study prior to and after provision of clinical information. A total of 87 cases were sampled (17 degenerative myelopathy, 53 neoplasia, nine inflammatory, and eight vascular). Magnetic resonance imaging had excellent (>97.6%) sensitivity for diagnosis of intradural spinal cord lesions but specificity varied before and after provision of clinical data (68.6% vs. 82.4%, P = 0.023). Magnetic resonance imaging had good sensitivity (86.8%) and moderate specificity (64.7-72.5%) for diagnosing neoplasia. Sensitivity was lower for classifying inflammatory lesions but improved with provision of clinical data (48.1% vs. 81.5%, P = 0.015). Magnetic resonance imaging was insensitive for diagnosing vascular lesions (25.0%). Interrater agreement was very good for correctly diagnosing dogs with intradural lesions (ĸ = 0.882-0.833), and good (ĸ = 0.726-0.671) for diagnosing dogs with neoplasia.
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http://dx.doi.org/10.1111/vru.12501DOI Listing
July 2017

Cranioplasty Using Titanium Mesh After Skull Tumor Resection in Five Dogs.

Vet Surg 2017 Jan 2;46(1):67-74. Epub 2016 Nov 2.

University of Georgia, College of Veterinary Medicine, Athens, Georgia.

Objective: To describe the clinical details, surgery, postoperative imaging, and short to mid-term outcome after cranioplasty with titanium mesh in dogs with large skull tumors.

Study Design: Case series.

Animals: Client-owned dogs with skull tumors (n=5).

Methods: All tumors were removed via craniectomy and a sheet of titanium mesh was contoured to reconstruct the calvarial defect and sutured to surrounding musculature.

Results: Four dogs had multilobular tumors of bone and 1 dog had a soft tissue sarcoma invading the cranial vault. Neurologic examination was unchanged or improved postoperative, a good cosmetic appearance was achieved, and no complications were noted at 2 weeks postoperative. Late postoperative computed tomography (CT) in 2 dogs and magnetic resonance (MR) imaging in 1 dog confirmed the presence of the titanium mesh without migration. There was no interference of the mesh with image interpretation and definitive radiation therapy was pursued in 1 dog without complication. Late follow-up reported 2 dogs euthanatized; at 44 weeks postoperative due to tumor re-growth; at 12 weeks postoperative for hemoabdomen, respectively. One dog drowned at 40 weeks postoperative, 1 dog was lost to follow-up, and 1 dog is alive at 83 weeks postoperative free of clinical signs.

Conclusions: Titanium mesh is suitable for cranioplasty based on its strength, biocompatibility, and excellent handling characteristics. It does not interfere with acquisition or interpretation of CT or MR images, thereby allowing postoperative imaging for ongoing assessment.
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http://dx.doi.org/10.1111/vsu.12577DOI Listing
January 2017