RESUMO
OBJECTIVE: Cruciate ligament rupture (CR) in Labrador Retrievers is a complex polygenic disease with high heritability. The environmental contribution to CR risk remains poorly characterized. An accurate genetic risk test for CR in the Labrador Retriever has been developed. This enables evaluation of environmental risk with knowledge of genetic disease predisposition through study of dogs with phenotypic disease status that is discordant with their genetic risk. The objective of this study was to identify environmental factors that contribute to CR in Labrador Retrievers through evaluation of dogs with clinical phenotypes that are discordantly predicted with the use of genetic markers. METHODS: Dogs were prospectively recruited between January 2013 and December 2022. To study discordant subjects, case dogs with a posterior risk probability value < 0.75 and control dogs with a posterior risk probability of > 0.25, determined with the use of an average of 8 statistical models, were selected. The environmental factors investigated were neuter status, age of neuter, withers height measured at the dorsal-most ridge between the scapulae, weight, body mass index, and athletic activity. RESULTS: Ninety three dogs were discordant: 58 dogs were discordant CR cases, and 35 dogs were discordant CR controls. Neutering before 12 months of age was a significant risk factor for CR development. Sex, neuter status, or status as an athlete was not associated with CR risk. CONCLUSIONS: Neutering before 12 months of age influences risk of CR in Labrador Retrievers. CLINICAL RELEVANCE: This information can inform management decisions about Labrador Retrievers regarding age of neutering, body condition, and athletic activity. The primary factor influencing CR development in Labrador Retrievers is polygenic intrinsic genetic risk.
RESUMO
OBJECTIVE: To investigate whether a humeral intracondylar fissure (HIF) alters bone strain in the French Bulldog humerus, we developed a quantitative CT-based 3-D finite element (FE) model for virtual mechanical testing. We hypothesized that higher strains would be seen in the intracondylar region and lateral epicondylar crest if there was a HIF. METHODS: Patient CT scans from 3 (n = 3) French Bulldogs were selected. Dog 1 had a closed distal physis and no HIF. Dog 2 had an open distal humeral physis but no HIF. Dog 3 had an open distal physis and a HIF. A 3-D FE model was built for FE analysis, and pressure was applied to the humerus over the region that contacts the radial head. RESULTS: The maximum principal bone strain patterns differed in each of the models. A path of strain concentration mimicking the typical pattern of a lateral condylar fracture was only found in dog 3. Maximum principal strain exceeded 1% in parts of the lateral epicondylar crest in all 3 dogs. CONCLUSIONS: We developed a patient-specific, quantitative CT-based 3-D FE model for virtual mechanical testing. We accepted our hypothesis. Strain concentration occurred in the intracondylar region and along the lateral epicondylar crest only when a HIF was present. CLINICAL RELEVANCE: The presence of a HIF in French Bulldogs elevates maximum principal bone strain in this region and alters its path in an FE model, which suggests an increased risk of a lateral humeral condylar fracture.
RESUMO
OBJECTIVE: To evaluate the radiation dose to personnel locations during simulated head and limb scans with a novel equine standing CT (sCT) system. METHODS: Measurements were made with the use of a helical fan beam sCT system (Equina; Asto CT Inc). Scatter radiation was measured in different positions in the sCT room to mimic the location of the control operator, horse handler, and lead rope handler during simulated equine head and limb imaging. Operator/handler dose was quantified at each location using entrance air kerma measured with a spherical ionization chamber and electrometer. RESULTS: Radiation dose to the control operator, horse handler, and lead rope handler locations wearing a lead apron during simulated head imaging was 13.3, 3.5, and 6.8 µGy, respectively. Radiation dose to the control operator location wearing a lead apron was 1.3 µGy, and dose to the lead rope handler location wearing a lead apron was 0.2 and 5.4 µGy during simulated pelvic limb and thoracic limb imaging, respectively. CONCLUSIONS: With the more widespread clinical use of equine sCT units in clinical practice, there is concern for increased risk of radiation exposure to personnel who stay in the sCT room during scanning. The control operator location had the highest dose during simulated head imaging, and the lead rope handler location in thoracic limb sCT had the highest dose during simulated limb imaging. Limiting the number of personnel in the sCT room, rotating personnel between handler positions, increasing operator distance from the scanner, and using lead shields and eyeglasses are recommended. CLINICAL RELEVANCE: Our findings suggest that scanning large numbers of horses per year with the Asto CT Equina would not lead to occupational radiation exposure above the recommended safe threshold for handlers using lead shields and eyeglasses.
RESUMO
BACKGROUND: Catastrophic injury has a low incidence but leads to the death of many Thoroughbred racehorses. OBJECTIVES: To determine sensitivity, specificity, and reliability for third metacarpal condylar stress fracture risk assessment from digital radiographs (DR) and standing computed tomography (sCT). STUDY DESIGN: Controlled ex vivo experiment. METHODS: A blinded set of metacarpophalangeal joint DR and sCT images were prepared from 31 Thoroughbreds. Four observers evaluated the condyles and parasagittal grooves (PSG) of the third metacarpal bone for the extent of dense bone and lucency/fissure and assigned a risk assessment grade for condylar stress fracture based on imaging features. Sensitivity and specificity for detection of subchondral structural changes in the condyles and PSG, and for risk assessment for condylar stress fracture were determined by comparison with a reference assessment based on sCT and joint surface examination. Agreement between observers and the reference assessment and reliability between observers were determined. Intra-observer repeatability was also assessed. RESULTS: Sensitivity for detection of structural change was lower than specificity for both imaging methods and all observers. For agreement with the reference assessment of structural change, correlation coefficients were generally below 0.5 for DR and 0.49-0.82 for sCT. For horses categorised as normal risk on reference assessment, observer assessment often agreed with the reference. Sensitivity for risk assessment was lower than specificity for all observers. For horses with a reference assessment of high risk of injury, observers generally underestimated risk. Diagnostic sensitivity of risk assessment was improved with sCT imaging, particularly for horses categorised as having elevated risk of injury from the reference assessment. Assessment repeatability and reliability was better with sCT than DR. MAIN LIMITATIONS: The ex vivo study design influenced DR image sets. CONCLUSIONS: Risk assessment through screening with diagnostic imaging is a promising approach to improve injury prevention in racing Thoroughbreds. Knowledge of sensitivity and specificity of fetlock lesion detection provides the critical guidance needed to improve racehorse screening programs. We found improved detection of MC3 subchondral structural change and risk assessment for condylar stress fracture with sCT ex vivo.
RESUMO
OBJECTIVE: Medical records for dogs treated with tibial plateau leveling osteotomy (TPLO) using Arthrex 3.5 mm self-tapping screws (STS) were evaluated to determine the incidence rate of transcortical tibial fractures (TCTF) and development of complications. STUDY DESIGN: Retrospective case report. STUDY POPULATION: A total of 78 dogs. METHODS: Dogs that underwent a TPLO performed from March 2022 to August 2023 were reviewed. Postoperative TPLO radiographs were examined for evidence of a TCTF with Arthrex 3.5 mm STS. Records were reviewed for complications up to 14 weeks after surgery. RESULTS: Evidence of a TCTF was found in 42% of cases (33 of 78) and 14% (36 of 250) of STS screws distal to the osteotomy. TCTFs were only identified distal to the osteotomy. Three dogs had radiographic evidence of more than one TCTF. Of the dogs with radiographic TCTF, 6% of patients (2 of 33) developed a major complication that required surgical stabilization of a tibial fracture associated with screw angulation relative to the plate. CONCLUSION: Use of Arthrex 3.5 mm STS for TPLO is associated with risk of TCTF. TCTF can compromise the structural properties of the tibia and cause complete tibial fracture requiring major revision surgery. CLINICAL SIGNIFICANCE: Development of TCTF after use of STS for TPLO has been recognized, in contrast to use of non-self-tapping screws, and was considered a benign complication. Our findings suggest TCTF associated with Arthrex 3.5 mm STS use in TPLO can contribute to major complications after surgery, including complete tibial fracture, particularly if screws are not placed perpendicular to the plate.
Assuntos
Parafusos Ósseos , Osteotomia , Fraturas da Tíbia , Animais , Cães/lesões , Osteotomia/veterinária , Osteotomia/efeitos adversos , Osteotomia/métodos , Fraturas da Tíbia/veterinária , Fraturas da Tíbia/cirurgia , Parafusos Ósseos/veterinária , Parafusos Ósseos/efeitos adversos , Estudos Retrospectivos , Feminino , Masculino , Doenças do Cão/cirurgia , Tíbia/cirurgia , Complicações Pós-Operatórias/veterináriaRESUMO
Nonpharmaceutical interventions introduced in the United Kingdom's response to the COVID-19 pandemic disrupted the transmission of other childhood infections. We report changes in seasonality, age dynamics and severity of respiratory syncytial virus infections between 2019 and 2023. These data show the potential effects of delaying respiratory syncytial virus exposure and may provide insights for the implementation of treatments preventing infection during early infancy.
RESUMO
BACKGROUND: Antibiotics are prescribed for over 50% of respiratory tract infections in primary care, despite good evidence of there being no benefit to the patient, and evidence of over prescribing driving microbial resistance. The high treatment rates are attributed to uncertainty regarding microbiological cause and clinical prognosis. Point-of-care-tests have been proposed as potential antibiotic stewardship tools, with some providing microbiological results in 15 minutes. However, there is little research on their impact on antibiotic use and clinical outcomes in primary care. METHODS: This is a multi-centre, individually randomised controlled trial with mixed-methods investigation of microbial, behavioural and antibiotic mechanisms on outcomes in patients aged 12 months and over presenting to primary care in the UK with a suspected respiratory tract infection, where the clinician and/or patient thinks antibiotic treatment may be, or is, necessary. Once consented, all participants are asked to provide a combined nose and throat swab sample and randomised to have a rapid microbiological point-of-care-test or no point-of-care-test. For intervention patients, clinicians review the result of the test, before contacting the patient to finalise treatment. Treatment decisions are made as per usual care in control group patients. The primary outcome is whether an antibiotic is prescribed at this point. All swab samples are sent to the central laboratory for further testing. Patients are asked to complete a diary to record the severity and duration of symptoms until resolution or day 28, and questionnaires at 2 months about their beliefs and intention to consult for similar future illnesses. Primary care medical records are also reviewed at 6-months to collect further infection consultations, antibiotic prescribing and hospital admissions. The trial aims to recruit 514 patients to achieve 90% power with 5% significance to detect a 15% absolute reduction in antibiotic prescribing. Qualitative interviews are being conducted with approximately 20 clinicians and 30 participants to understand any changes in beliefs and behaviour resulting from the point-of-care-test and generate attributes for clinician and patient discrete choice experiments. DISCUSSION: This trial will provide evidence of efficacy, acceptability and mechanisms of action of a rapid microbiological point-of-care test on antibiotic prescribing and patient symptoms in primary care. TRIAL REGISTRATION: ISRCTN16039192, prospectively registered on 08/11/2022.
Assuntos
Antibacterianos , Testes Imediatos , Atenção Primária à Saúde , Infecções Respiratórias , Feminino , Humanos , Masculino , Antibacterianos/uso terapêutico , Gestão de Antimicrobianos/métodos , Sistemas Automatizados de Assistência Junto ao Leito , Ensaios Clínicos Controlados Aleatórios como Assunto , Infecções Respiratórias/tratamento farmacológico , Infecções Respiratórias/microbiologia , Infecções Respiratórias/diagnóstico , Estudos Multicêntricos como AssuntoRESUMO
Objective: The objective of this study was to examine outcomes in dogs with cruciate ligament rupture (CR) that had chronic radiographic cranial tibial subluxation at the time of osteotomy healing after tibial plateau leveling osteotomy (TPLO). Study Design. Retrospective case analysis of 12 dogs with prospective follow-up. Four of the 12 dogs were prospectively studied 12-24 months after surgery to assess long-term radiographic and clinical outcomes. Results: Three of the 4 dogs showed improvement in radiographic cranial tibial subluxation at long-term follow-up. In the other dog, minimally improved cranial tibial subluxation was associated with severe lameness. At long-term follow-up, gait analysis in 3 dogs with improved subluxation showed the symmetry of weight-bearing within 10% for peak vertical force, and no clinically lameness. Preoperative tibial plateau angle (TPA) and radiographic osteoarthritis in dogs with prospective follow-up and all dogs treated with TPLO surgery in the study period were not significantly different. Conclusion: Dogs with chronic radiographic cranial tibial subluxation are acceptable candidates for TPLO. Radiographic improvement in stifle reduction may take more than 10 weeks. The dog with long-term persistent subluxation also had a higher TPA over time, suggestive of ineffective surgical correction with TPLO and treatment failure.
Assuntos
Doenças dos Cavalos , Corrida , Cavalos , Animais , Doenças dos Cavalos/prevenção & controleRESUMO
Condylar stress fracture of the distal end of the third metacarpal/metatarsal (MC3/MT3) bones is a major cause of Thoroughbred racehorse injury and euthanasia worldwide. Functional adaptation to exercise and fatigue damage lead to structural changes in the subchondral bone that include increased modeling (resulting in sclerotic bone tissue) and targeted remodeling repair (resulting in focal resorption spaces in the parasagittal groove). Whether these focal structural changes, as detectable by standing computed tomography (sCT), lead to elevated strain at the common site of condylar stress fracture has not been demonstrated. Therefore, the goal of the present study was to compare full-field three-dimensional (3D) strain on the distopalmar aspect of MC3 bone specimens with and without focal subchondral bone injury (SBI). Thirteen forelimb specimens were collected from racing Thoroughbreds for mechanical testing ex vivo and underwent sCT. Subsequently, full-field displacement and strain at the joint surface were determined using stereo digital image correlation. Strain concentration was observed in the parasagittal groove (PSG) of the loaded condyles, and those with SBI in the PSG showed higher strain rates in this region than control bones. PSG strain rate in condyles with PSG SBI was more sensitive to CT density distribution in comparison with condyles with no sCT-detectable injury. Findings from this study help to interpret structural changes in the subchondral bone due to fatigue damage and to assess risk of incipient stress fracture in a patient-specific manner.
Assuntos
Ossos Metacarpais , Estresse Mecânico , Animais , Cavalos , Ossos Metacarpais/diagnóstico por imagem , Fenômenos Biomecânicos , Testes Mecânicos , Tomografia Computadorizada por Raios X , Fraturas de Estresse/diagnóstico por imagem , Fraturas de Estresse/patologiaRESUMO
Late-onset peripheral neuropathy (LPN) is a heritable canine neuropathy commonly found in Labrador retrievers and is characterized by laryngeal paralysis and pelvic limb paresis. Our objective was to establish canine LPN as a model for human hereditary peripheral neuropathy by classifying it as either an axonopathy or myelinopathy and evaluating length-dependent degeneration. We conducted a motor nerve conduction study of the sciatic and ulnar nerves, electromyography (EMG) of appendicular and epaxial musculature, and histologic analysis of sciatic and recurrent laryngeal nerves in LPN-affected and control dogs. LPN-affected dogs exhibited significant decreases in compound muscle action potential (CMAP) amplitude, CMAP area, and pelvic limb latencies. However, no differences were found in motor nerve conduction velocity, residual latencies, or CMAP duration. Distal limb musculature showed greater EMG changes in LPN-affected dogs. Histologically, LPN-affected dogs exhibited a reduction in the number of large-diameter axons, especially in distal nerve regions. In conclusion, LPN in Labrador retrievers is a common, spontaneous, length-dependent peripheral axonopathy that is a novel animal model of age-related peripheral neuropathy that could be used for fundamental research and clinical trials.
Assuntos
Doenças do Sistema Nervoso Periférico , Humanos , Animais , Cães , Axônios , Eletromiografia , Extremidades , Membro PosteriorRESUMO
BACKGROUND: Prompt identification of patients with severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection on admission to hospital is crucial to ensuring initiation of appropriate treatment, optimising infection control and maintaining patient flow. The Abbott ID NOW™ COVID-19 assay (ID NOW) is a point-of-care, isothermal nucleic acid amplification test, capable of producing a result within minutes, potentially placing it as an invaluable tool in helping to control the coronavirus-disease 2019 (COVID-19) pandemic. OBJECTIVES: To evaluate the diagnostic accuracy of ID NOW in acute hospital admissions. STUDY DESIGN: A prospective approach to data collection was undertaken in consecutive patients with ID NOW and Hologic Aptima™ SARS-CoV-2 transcription-mediated amplification assay (Aptima TMA) results, across three hospitals in the south-west of England between 1st March and 30th September 2021. A nasal swab was taken for ID NOW and a combined nose and throat swab for Aptima TMA. Measures of diagnostic accuracy were calculated for ID NOW against Aptima TMA. This study was conducted during a period of alpha and delta strain predominance. RESULTS: 19,698 ID NOW assays were performed, of which 12,821 had an Aptima TMA assay performed within 24 hours. ID NOW had sensitivity of 85.2 % (95 % CI, 82.2-87.9) and specificity of 99.6 % (95 % CI, 99.4-99.7) compared with the reference assay. The overall PPV was 91.0 % (95 % CI, 88.5-93.0) and the overall NPV was 99.3 % (95 % CI, 99.1-99.4). CONCLUSIONS: ID NOW offers a valid diagnostic tool to detect SARS-CoV-2, performing comparably to a reference laboratory-based assay which takes longer to provide results.
Assuntos
COVID-19 , Humanos , COVID-19/diagnóstico , SARS-CoV-2 , Técnicas de Laboratório Clínico/métodos , Teste para COVID-19 , Sensibilidade e Especificidade , Testes Imediatos , HospitaisRESUMO
BACKGROUND: Resistance to antibiotics is rising and threatens future antibiotic effectiveness. 'Antibiotic targeting' ensures patients who may benefit from antibiotics receive them, while being safely withheld from those who may not. Point-of-care tests may assist with antibiotic targeting by allowing primary care clinicians to establish if symptomatic patients have a viral, bacterial, combined, or no infection. However, because organisms can be harmlessly carried, it is important to know if the presence of the virus/bacteria is related to the illness for which the patient is being assessed. One way to do this is to look for associations with more severe/prolonged symptoms and test results. Previous research to answer this question for acute respiratory tract infections has given conflicting results with studies has not having enough participants to provide statistical confidence. AIM: To undertake a synthesis of IPD from both randomised controlled trials (RCTs) and observational cohort studies of respiratory tract infections (RTI) in order to investigate the prognostic value of microbiological data in addition to, or instead of, clinical symptoms and signs. METHODS: A systematic search of Cochrane Central Register of Controlled Trials, Ovid Medline and Ovid Embase will be carried out for studies of acute respiratory infection in primary care settings. The outcomes of interest are duration of disease, severity of disease, repeated consultation with new/worsening illness and complications requiring hospitalisation. Authors of eligible studies will be contacted to provide anonymised individual participant data. The data will be harmonised and aggregated. Multilevel regression analysis will be conducted to determine key outcome measures for different potential pathogens and whether these offer any additional information on prognosis beyond clinical symptoms and signs. TRIAL REGISTRATION: PROSPERO Registration number: CRD42023376769.
Assuntos
Antibacterianos , Infecções Respiratórias , Humanos , Antibacterianos/uso terapêutico , Infecções Respiratórias/tratamento farmacológico , Infecções Respiratórias/complicações , Metanálise como AssuntoRESUMO
Canine anterior cruciate ligament (ACL) rupture is a common complex disease. Prevalence of ACL rupture is breed dependent. In an epidemiological study, yellow coat color was associated with increased risk of ACL rupture in the Labrador Retriever. ACL rupture risk variants may be linked to coat color through genetic selection or through linkage with coat color genes. To investigate these associations, Labrador Retrievers were phenotyped as ACL rupture case or controls and for coat color and were single nucleotide polymorphism (SNP) genotyped. After filtering, ~ 697 K SNPs were analyzed using GEMMA and mvBIMBAM for multivariate association. Functional annotation clustering analysis with DAVID was performed on candidate genes. A large 8 Mb region on chromosome 5 that included ACSF3, as well as 32 additional SNPs, met genome-wide significance at P < 6.07E-7 or Log10(BF) = 3.0 for GEMMA and mvBIMBAM, respectively. On chromosome 23, SNPs were located within or near PCCB and MSL2. On chromosome 30, a SNP was located within IGDCC3. SNPs associated with coat color were also located within ADAM9, FAM109B, SULT1C4, RTDR1, BCR, and RGS7. DZIP1L was associated with ACL rupture. Several significant SNPs on chromosomes 2, 3, 7, 24, and 26 were located within uncharacterized regions or long non-coding RNA sequences. This study validates associations with the previous ACL rupture candidate genes ACSF3 and DZIP1L and identifies novel candidate genes. These variants could act as targets for treatment or as factors in disease prediction modeling. The study highlighted the importance of regulatory SNPs in the disease, as several significant SNPs were located within non-coding regions.
Assuntos
Lesões do Ligamento Cruzado Anterior , Ligamento Cruzado Anterior , Cães , Animais , Lesões do Ligamento Cruzado Anterior/genética , Genótipo , Polimorfismo de Nucleotídeo Único/genética , FenótipoRESUMO
Enteroviruses are a common cause of seasonal childhood infections. The vast majority of enterovirus infections are mild and self-limiting, although neonates can sometimes develop severe disease. Myocarditis is a rare complication of enterovirus infection. Between June 2022 and April 2023, twenty cases of severe neonatal enteroviral myocarditis caused by coxsackie B viruses were reported in the United Kingdom. Sixteen required critical care support and two died. Enterovirus PCR on whole blood was the most sensitive diagnostic test. We describe the initial public health investigation into this cluster and aim to raise awareness among paediatricians, laboratories and public health specialists.
Assuntos
Infecções por Enterovirus , Enterovirus , Miocardite , Recém-Nascido , Humanos , Criança , Miocardite/diagnóstico , Miocardite/complicações , Infecções por Enterovirus/complicações , Infecções por Enterovirus/diagnóstico , Enterovirus/genética , Enterovirus Humano B/genética , Saúde PúblicaRESUMO
We conducted a feasibility cohort study which aimed to recruit and retain adults from the community to collect saliva (oral) and stool (gut) samples at three time points, at the start of the study (baseline), during a respiratory tract infection (RTI) and post-RTI. Community RTIs place a huge burden on health care services, and a non-invasive microbial diagnostic tool to predict the most vulnerable to respiratory infection would be ideal. To this aim, we analysed oral-gut baseline samples comparing those who reported RTI symptoms to those who remained healthy throughout the study for microbial biomarkers of respiratory susceptibility. Amplicon sequence variants (ASV) were identified by 16S sequence profiling to reveal oral-gut microbes. Reverse transcriptase-polymerase chain reaction (RT-PCR) was applied to target common respiratory microbes. Two general practices were recruited, and the participant recruitment rate was 1.3%. A total of 40 adult participants were retained, of which 19 acquired an RTI whereas 21 remained healthy. In healthy baseline oral and gut samples, ASVs from participants with RTI symptoms compared to those who remained healthy were similar with a high relative abundance of Streptococcus sp., and Blautia sp., respectively. Linear discriminant analysis effect size (LEfSe) revealed baseline oral microbes differed, indicating participants who suffered RTI symptoms had enhanced Streptococcus sobrinus and Megamonas sp., and depletion of Lactobacillus salivarius, Synergistetes, Verrucomicrobia and Dethiosulfovibrio. Furthermore, a random forest model ranked Streptococcus (4.13) as the highest mean decrease in accuracy (MDA) and RT-PCR showed a higher level of carriage of coagulase-negative Staphylococcus. Baseline core gut microbes were similar in both participant groups whereas LEfSe analysis revealed enhanced Veillonella, Rikenellaceae, Enhydobacteria, Eggerthella and Xanthomonsdales and depleted Desulfobulbus and Coprobacillus. Sutterella (4.73) had a high MDA value. Overall, we demonstrated the feasibility of recruiting and retaining adult participants from the community to provide multiple biological samples for microbial profiling. Our analyses identified potential oral-gut microbial biomarkers of respiratory infection susceptibility in otherwise healthy participants.
RESUMO
Introduction: Spontaneous rupture of tendons and ligaments is common in several species including humans. In horses, degenerative suspensory ligament desmitis (DSLD) is an important acquired idiopathic disease of a major energy-storing tendon-like structure. DSLD risk is increased in several breeds, including the Peruvian Horse. Affected horses have often been used for breeding before the disease is apparent. Breed predisposition suggests a substantial genetic contribution, but heritability and genetic architecture of DSLD have not been determined. Methods: To identify genomic regions associated with DSLD, we recruited a reference population of 183 Peruvian Horses, phenotyped as DSLD cases or controls, and undertook a genome-wide association study (GWAS), a regional window variance analysis using local genomic partitioning, a signatures of selection (SOS) analysis, and polygenic risk score (PRS) prediction of DSLD risk. We also estimated trait heritability from pedigrees. Results: Heritability was estimated in a population of 1,927 Peruvian horses at 0.22 ± 0.08. After establishing a permutation-based threshold for genome-wide significance, 151 DSLD risk single nucleotide polymorphisms (SNPs) were identified by GWAS. Multiple regions of enriched local heritability were identified across the genome, with strong enrichment signals on chromosomes 1, 2, 6, 10, 13, 16, 18, 22, and the X chromosome. With SOS analysis, there were 66 genes with a selection signature in DSLD cases that was not present in the control group that included the TGFB3 gene. Pathways enriched in DSLD cases included proteoglycan metabolism, extracellular matrix homeostasis, and signal transduction pathways that included the hedgehog signaling pathway. The best PRS predictive performance was obtained when we fitted 1% of top SNPs using a Bayesian Ridge Regression model which achieved the highest mean of R2 on both the probit and logit liability scales, indicating a strong predictive performance. Discussion: We conclude that within-breed GWAS of DSLD in the Peruvian Horse has further confirmed that moderate heritability and a polygenic architecture underlies the trait and identified multiple DSLD SNP associations in novel tendinopathy candidate genes influencing disease risk. Pathways enriched with DSLD risk variants include ones that influence glycosaminoglycan metabolism, extracellular matrix homeostasis, signal transduction pathways.
RESUMO
OBJECTIVE: To determine the presentation, diagnosis, progression, and family risk of fibrotic myopathy, a disease with marked breed predisposition in the German Shepherd Dog (GSD). ANIMALS: 41 dogs prospectively recruited to the University of Wisconsin-Madison Comparative Genetics and Orthopedic Laboratory between November 2019 to August 2022. METHODS: Medical records of dogs diagnosed with fibrotic myopathy were reviewed upon referral. The following data were recorded: sex, age, weight, regio interscapularis (withers) height, date of neutering, coat color and length, and age at fibrotic myopathy diagnosis. A pedigree was also obtained. RESULTS: In the study population, breeds included 37 GSDs, a Belgian Malinois, a Belgian Malinois cross, and 2 dogs with a GSD phenotype and no pedigree. Mean age at fibrotic myopathy diagnosis was 5.9 ± 2.0 years, and duration of lameness before diagnosis was 5.6 months and ranged from 0.75 to 18 months. Males were overrepresented at 61% of the study population. Inherited familial risk for fibrotic myopathy in the GSD was supported by pedigree analysis. CLINICAL RELEVANCE: This was the largest case series of fibrotic myopathy to date, providing a more comprehensive look at presentation and progression of the disease. The longer duration of lameness in bilaterally affected dogs likely represents disease progression rather than a more severe phenotype. Family history data support a genetic contribution to fibrotic myopathy, suggesting that further genetic investigation is warranted.
Assuntos
Contratura , Doenças do Cão , Doenças Musculares , Humanos , Masculino , Cães , Animais , Estudos Prospectivos , Coxa da Perna , Coxeadura Animal , Doenças Musculares/genética , Doenças Musculares/veterinária , Contratura/genética , Contratura/veterinária , Doenças do Cão/genéticaRESUMO
Implant failure is common in small animal orthopedics, but risk factors are rarely reported. Our objective was to determine whether abnormal fracture healing was associated with implant failure after fracture fixation in dogs and cats in a consecutive series of cases. Thirty-seven client-owned animals (thirty-two dogs, five cats) diagnosed with implant failure after fracture treatment from January 2013-September 2018 were studied. Medical and radiographic records were retrospectively reviewed to identify patients that underwent fracture fixation using open reduction and internal fixation with subsequent radiographic evidence of implant failure. Area moment of inertia (AMI), plate working length, and bone screw density were determined. Implant failure was found in 39 fractures in 37 animals, representing 23% of fracture cases during the study period. Cases of implant failure were at increased risk of delayed union, malunion, or non-union (p < 0.0001). The most common cause of implant failure was loosening (54%); the second most common was plate failure that included low AMI locking plates (28%). Major complications found in 22/39 fractures (56%) were associated with delayed union (p < 0.01). Surgical revision was performed in 49% of implant failure cases. Complications were most frequently identified after treatment of humeral fractures (26%). We conclude mechanical failure of implants increases the risk for delayed or abnormal fracture healing and often requires revision surgery. Implant AMI should be considered during preoperative planning. Locking plates are associated with implant failure if plate bending stiffness is not sufficient, based on findings from this case series.