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During the current coronavirus disease 2019 (COVID-19) pandemic, a variety of mutations have accumulated in the viral genome of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and, at the time of writing, four variants of concern are considered to be potentially hazardous to human society1. The recently emerged B.1.617.2/Delta variant of concern is closely associated with the COVID-19 surge that occurred in India in the spring of 2021 (ref. 2). However, the virological properties of B.1.617.2/Delta remain unclear. Here we show that the B.1.617.2/Delta variant is highly fusogenic and notably more pathogenic than prototypic SARS-CoV-2 in infected hamsters. The P681R mutation in the spike protein, which is highly conserved in this lineage, facilitates cleavage of the spike protein and enhances viral fusogenicity. Moreover, we demonstrate that the P681R-bearing virus exhibits higher pathogenicity compared with its parental virus. Our data suggest that the P681R mutation is a hallmark of the virological phenotype of the B.1.617.2/Delta variant and is associated with enhanced pathogenicity.
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COVID-19/virología , Fusión de Membrana , Mutación , SARS-CoV-2/genética , SARS-CoV-2/patogenicidad , Glicoproteína de la Espiga del Coronavirus/genética , Sustitución de Aminoácidos , Animales , Anticuerpos Neutralizantes/inmunología , Anticuerpos Antivirales/inmunología , COVID-19/epidemiología , Cricetinae , Células Gigantes/metabolismo , Células Gigantes/virología , Masculino , Mesocricetus , Filogenia , SARS-CoV-2/inmunología , SARS-CoV-2/metabolismo , Virulencia/genética , Replicación ViralRESUMEN
The recent emergence of SARS-CoV-2 Omicron (B.1.1.529 lineage) variants possessing numerous mutations has raised concerns of decreased effectiveness of current vaccines, therapeutic monoclonal antibodies and antiviral drugs for COVID-19 against these variants1,2. The original Omicron lineage, BA.1, prevailed in many countries, but more recently, BA.2 has become dominant in at least 68 countries3. Here we evaluated the replicative ability and pathogenicity of authentic infectious BA.2 isolates in immunocompetent and human ACE2-expressing mice and hamsters. In contrast to recent data with chimeric, recombinant SARS-CoV-2 strains expressing the spike proteins of BA.1 and BA.2 on an ancestral WK-521 backbone4, we observed similar infectivity and pathogenicity in mice and hamsters for BA.2 and BA.1, and less pathogenicity compared with early SARS-CoV-2 strains. We also observed a marked and significant reduction in the neutralizing activity of plasma from individuals who had recovered from COVID-19 and vaccine recipients against BA.2 compared to ancestral and Delta variant strains. In addition, we found that some therapeutic monoclonal antibodies (REGN10987 plus REGN10933, COV2-2196 plus COV2-2130, and S309) and antiviral drugs (molnupiravir, nirmatrelvir and S-217622) can restrict viral infection in the respiratory organs of BA.2-infected hamsters. These findings suggest that the replication and pathogenicity of BA.2 is similar to that of BA.1 in rodents and that several therapeutic monoclonal antibodies and antiviral compounds are effective against Omicron BA.2 variants.
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Antivirales , Tratamiento Farmacológico de COVID-19 , SARS-CoV-2 , Animales , Anticuerpos Monoclonales/farmacología , Anticuerpos Monoclonales/uso terapéutico , Anticuerpos Monoclonales Humanizados , Anticuerpos Neutralizantes/farmacología , Anticuerpos Neutralizantes/uso terapéutico , Anticuerpos Antivirales/farmacología , Anticuerpos Antivirales/uso terapéutico , Antivirales/farmacología , Antivirales/uso terapéutico , COVID-19/genética , COVID-19/inmunología , COVID-19/virología , Cricetinae , Citidina/análogos & derivados , Combinación de Medicamentos , Hidroxilaminas , Indazoles , Lactamas , Leucina , Ratones , Nitrilos , Prolina , SARS-CoV-2/efectos de los fármacos , SARS-CoV-2/genética , SARS-CoV-2/patogenicidad , Glicoproteína de la Espiga del Coronavirus/genética , Triazinas , TriazolesRESUMEN
The recent emergence of B.1.1.529, the Omicron variant1,2, has raised concerns of escape from protection by vaccines and therapeutic antibodies. A key test for potential countermeasures against B.1.1.529 is their activity in preclinical rodent models of respiratory tract disease. Here, using the collaborative network of the SARS-CoV-2 Assessment of Viral Evolution (SAVE) programme of the National Institute of Allergy and Infectious Diseases (NIAID), we evaluated the ability of several B.1.1.529 isolates to cause infection and disease in immunocompetent and human ACE2 (hACE2)-expressing mice and hamsters. Despite modelling data indicating that B.1.1.529 spike can bind more avidly to mouse ACE2 (refs. 3,4), we observed less infection by B.1.1.529 in 129, C57BL/6, BALB/c and K18-hACE2 transgenic mice than by previous SARS-CoV-2 variants, with limited weight loss and lower viral burden in the upper and lower respiratory tracts. In wild-type and hACE2 transgenic hamsters, lung infection, clinical disease and pathology with B.1.1.529 were also milder than with historical isolates or other SARS-CoV-2 variants of concern. Overall, experiments from the SAVE/NIAID network with several B.1.1.529 isolates demonstrate attenuated lung disease in rodents, which parallels preliminary human clinical data.
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COVID-19/patología , COVID-19/virología , Modelos Animales de Enfermedad , SARS-CoV-2/patogenicidad , Enzima Convertidora de Angiotensina 2/genética , Enzima Convertidora de Angiotensina 2/metabolismo , Animales , Cricetinae , Femenino , Humanos , Pulmón/patología , Pulmón/virología , Masculino , Mesocricetus , Ratones , Ratones Endogámicos BALB C , Ratones Endogámicos C57BL , Ratones Transgénicos , Carga ViralRESUMEN
The spike (S) protein of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) plays a key role in viral infectivity. It is also the major antigen stimulating the host's protective immune response, specifically, the production of neutralizing antibodies. Recently, a new variant of SARS-CoV-2 possessing multiple mutations in the S protein, designated P.1, emerged in Brazil. Here, we characterized a P.1 variant isolated in Japan by using Syrian hamsters, a well-established small animal model for the study of SARS-CoV-2 disease (COVID-19). In hamsters, the variant showed replicative abilities and pathogenicity similar to those of early and contemporary strains (i.e., SARS-CoV-2 bearing aspartic acid [D] or glycine [G] at position 614 of the S protein). Sera and/or plasma from convalescent patients and BNT162b2 messenger RNA vaccinees showed comparable neutralization titers across the P.1 variant, S-614D, and S-614G strains. In contrast, the S-614D and S-614G strains were less well recognized than the P.1 variant by serum from a P.1-infected patient. Prior infection with S-614D or S-614G strains efficiently prevented the replication of the P.1 variant in the lower respiratory tract of hamsters upon reinfection. In addition, passive transfer of neutralizing antibodies to hamsters infected with the P.1 variant or the S-614G strain led to reduced virus replication in the lower respiratory tract. However, the effect was less pronounced against the P.1 variant than the S-614G strain. These findings suggest that the P.1 variant may be somewhat antigenically different from the early and contemporary strains of SARS-CoV-2.
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COVID-19/virología , SARS-CoV-2/fisiología , SARS-CoV-2/patogenicidad , Replicación Viral , Animales , Anticuerpos Neutralizantes , COVID-19/diagnóstico por imagen , COVID-19/patología , Cricetinae , Humanos , Inmunogenicidad Vacunal , Pulmón/patología , Mesocricetus , Ratones , Glicoproteína de la Espiga del Coronavirus/genética , Microtomografía por Rayos XRESUMEN
OBJECTIVE: To describe the technique for anastomosis of the caudal thoracic duct (TD) to the 10th or 11th intercostal vein (ICV) using a microvascular anastomotic coupler (MAC) device in dogs and assess patency of the anastomosis on days 0 and 30. STUDY DESIGN: Experimental study. SAMPLE POPULATION: Six adult Beagle dogs. METHODS: Under general anesthesia, fluoroscopic popliteal lymphangiography was performed and the TD identified. A right ninth or 10th intercostal thoracotomy was performed. Using an operating microscope, the TD and the 10th or 11th ICV were isolated, ligated, and anastomosed using a 1.5 or 2.0 mm MAC. Fluoroscopic popliteal lymphangiography was repeated immediately after surgery and on day 30. RESULTS: The anastomosis was successful and lymphangiography documented flow into the azygos vein in all six dogs immediately after surgery. At day 30, the anastomosis was patent in four of six dogs. In two dogs, flow through the anastomosis was obstructed due to kinking of the ICV just cranial to the MAC. CONCLUSION: Anastomosis of the TD and ICV using a MAC was feasible and was shown to maintain patency up to 30 days. When performing the anastomosis, care should be taken to ensure the ICV is not kinked by the MAC. CLINICAL SIGNIFICANCE: Direct anastomosis of the TD and ICV may have application for treatment of idiopathic chylothorax in dogs by maintaining flow from the abdominal lymphatics to the central venous circulation and thereby preventing the stimulus for collateral circulation and persistent chylous effusion. Further investigation is warranted to assess the efficacy of this technique in dogs affected with idiopathic chylothorax.
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OBJECTIVE: The aim of this study was to describe a technique for anastomosis of the thoracic duct (TD) to the azygos vein (AV) using a microvascular anastomotic coupler (MAC) device in feline cadavers. Our hypothesis was that a TD-AV lymphaticovenous anastomosis would be feasible in feline cadavers. STUDY DESIGN: Cadaveric study. ANIMALS: Eight domestic shorthair feline cadavers. METHODS: A left paracostal laparotomy and 9th or 10th intercostal thoracotomy was performed. Contrast media was injected into a mesenteric lymph node and lymphography was used to identify the TD and its branches. The TD and AV were isolated, ligated, and divided with the aid of a surgical microscope. The TD and AV were anastomosed end-to-end using a 1.5 or 2.0 mm MAC. Intraoperative patency was assessed by manipulation of chyle and venous blood across the anastomosis. Mesenteric lymphography was repeated to confirm postoperative anastomotic patency. RESULTS: The TD was identified via lymphography in seven of eight cats. The anastomosis was successful and patency was confirmed via intraoperative assessment and postoperative lymphography in all cats. The median (range) duration for the dissection and anastomosis portions of the procedure was 122 (80-150) min. CONCLUSION: End-to-end anastomosis of the TD to the AV using a MAC was feasible in the feline cadaver without major intraoperative technical challenges. CLINICAL SIGNIFICANCE: Anastomosis of the TD and AV may have application as an alternative treatment for idiopathic chylothorax in cats. By directly connecting the abdominal lymphatics to the central venous system, the stimulus for collateral vessel development around the site of TD ligation may be minimized, which may prevent leakage of chyle through the more cranial lymphatics.
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Exocrine pancreatic carcinomas are uncommon in dogs and cats, and diagnosis with diagnostic imaging can be challenging. This retrospective, multi-institutional, descriptive study was performed to evaluate the CT features of exocrine pancreatic carcinomas. The CT examinations of 18 dogs and 12 cats with exocrine pancreatic carcinomas diagnosed by cytology or histopathology were reviewed. The CT features of exocrine pancreatic carcinomas included a well-defined mass in 28/30 (93%) with contrast enhancement in 27/30 (90%), commonly heterogeneous 22/30 (73%); often with a nonenhancing fluid to soft tissue attenuating center 12/30 (40%). The right lobe of the pancreas was the most common location, 14/30 (47%), then the left lobe, 10/30 (33%), and the body, 6/30 (20%). Extrahepatic biliary duct dilation was present in six animals; 5/6 (83%) of the masses were located in the right pancreatic lobe. Additional findings included peripancreatic fat-stranding 17/30 (57%), lymphadenopathy 16/30 (57%), peripancreatic soft tissue nodules 12/30 (40%), and free fluid 10/30 (33%). When comparing the imaging features of dogs and cats, there was a large overlap in imaging characteristics. There was a significant difference between the height of the masses, with dogs having larger masses (P-value.0028). Lymphadenopathy was more likely in larger masses [increased height (P-value.029)]. Cats were significantly older than dogs (P-value.0355). Pancreatic carcinomas were commonly identified as masses with heterogeneous contrast enhancement and a nonenhancing fluid to soft tissue attenuating center with concurrent peripancreatic changes (fat-stranding and/or soft tissue nodules) and lymphadenopathy.
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Enfermedades de los Gatos , Enfermedades de los Perros , Neoplasias Pancreáticas , Tomografía Computarizada por Rayos X , Animales , Perros , Gatos , Enfermedades de los Gatos/diagnóstico por imagen , Enfermedades de los Gatos/patología , Enfermedades de los Perros/diagnóstico por imagen , Enfermedades de los Perros/patología , Neoplasias Pancreáticas/veterinaria , Neoplasias Pancreáticas/diagnóstico por imagen , Neoplasias Pancreáticas/patología , Estudios Retrospectivos , Tomografía Computarizada por Rayos X/veterinaria , Masculino , Femenino , Carcinoma/veterinaria , Carcinoma/diagnóstico por imagen , Carcinoma/patologíaRESUMEN
At the end of 2019, a novel coronavirus (severe acute respiratory syndrome coronavirus 2; SARS-CoV-2) was detected in Wuhan, China, that spread rapidly around the world, with severe consequences for human health and the global economy. Here, we assessed the replicative ability and pathogenesis of SARS-CoV-2 isolates in Syrian hamsters. SARS-CoV-2 isolates replicated efficiently in the lungs of hamsters, causing severe pathological lung lesions following intranasal infection. In addition, microcomputed tomographic imaging revealed severe lung injury that shared characteristics with SARS-CoV-2-infected human lung, including severe, bilateral, peripherally distributed, multilobular ground glass opacity, and regions of lung consolidation. SARS-CoV-2-infected hamsters mounted neutralizing antibody responses and were protected against subsequent rechallenge with SARS-CoV-2. Moreover, passive transfer of convalescent serum to naïve hamsters efficiently suppressed the replication of the virus in the lungs even when the serum was administrated 2 d postinfection of the serum-treated hamsters. Collectively, these findings demonstrate that this Syrian hamster model will be useful for understanding SARS-CoV-2 pathogenesis and testing vaccines and antiviral drugs.
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Infecciones por Coronavirus/virología , Modelos Animales de Enfermedad , Pulmón/patología , Neumonía Viral/virología , Animales , Anticuerpos Neutralizantes/sangre , Anticuerpos Antivirales/sangre , Betacoronavirus/patogenicidad , Betacoronavirus/fisiología , COVID-19 , Línea Celular , Chlorocebus aethiops , Infecciones por Coronavirus/patología , Infecciones por Coronavirus/terapia , Cricetinae , Humanos , Inmunización Pasiva , Pulmón/diagnóstico por imagen , Pulmón/virología , Mesocricetus , Pandemias , Neumonía Viral/patología , Ribonucleoproteínas/química , SARS-CoV-2 , Células Vero , Proteínas Virales/química , Replicación Viral , Sueroterapia para COVID-19RESUMEN
A 2-year-old male neutered Rat Terrier was presented for alopecia, recurrent urinary tract infections, and urinary incontinence. Abdominal ultrasound and CT identified a thin, tubular, paired structure arising from the craniodorsal aspect of an enlarged, cystic prostate. An atypical uterus masculinus was initially suspected, however it was then identified that the patient had chronic exogenous estrogen exposure, and surgical resection and histopathology was consistent with an enlarged and inflamed vas deferens. Vas deferens enlargement and vasitis secondary to chronic hyperestrogenism should be considered for a tubular, paired structure arising from the craniodorsal prostate in a male dog.
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Próstata , Conducto Deferente , Animales , Perros , Estrógenos/efectos adversos , Femenino , Masculino , Próstata/diagnóstico por imagen , Tomografía Computarizada por Rayos X , Ultrasonografía/veterinaria , Conducto Deferente/diagnóstico por imagen , Conducto Deferente/patologíaRESUMEN
A 14-week-old male unilaterally cryptorchid Clumber spaniel was presented for acute lethargy. Physical examination revealed abdominal pain, and a single testis was palpated in the scrotum. Abdominal ultrasound and computed tomography (CT) revealed a poorly vascularized, ovoid structure immediately caudal to the left kidney with scant regional peritoneal effusion. Left intra-abdominal testicular torsion was confirmed at surgery, and routine cryptorchidectomy was performed. The patient recovered uneventfully from anesthesia and surgery. Key clinical message: The most common CT characteristics of testicular torsion were present in this case and correlated well with sonographic findings to allow for rapid, accurate diagnosis and surgical planning of unilateral, non-neoplastic, intra-abdominal cryptorchid testicular torsion in a juvenile dog. Contrast enhanced CT facilitated accurate localization of the undescended testis and evaluation of testicular perfusion and may be a useful alternative to ultrasound for diagnosing testicular torsion, especially in indeterminate cases.
Tomodensitométrie d'une torsion testiculaire chez un chien juvénile atteint de cryptorchidie unilatérale. Un épagneul Clumber avec une cryptorchidie unilatérale âgé de 14 semaines a été présenté pour une léthargie aiguë. L'examen physique a révélé des douleurs abdominales et un seul testicule a été palpé dans le scrotum. L'échographie abdominale et la tomodensitométrie ont révélé une structure ovoïde mal vascularisée immédiatement caudale au rein gauche avec peu d'épanchement péritonéal régional. Une torsion testiculaire intra-abdominale gauche a été confirmée lors de la chirurgie et une cryptorchidectomie de routine a été réalisée. Le patient s'est remis sans incident de l'anesthésie et de la chirurgie.Message clinique clé:Les caractéristiques tomodensitométriques les plus courantes de la torsion testiculaire étaient présentes dans ce cas et bien corrélées avec les résultats échographiques pour permettre un diagnostic rapide et précis et une planification chirurgicale de la torsion testiculaire avec cryptorchidie unilatérale, non néoplasique et intra-abdominale chez un chien juvénile. La tomodensitométrie avec contraste a facilité la localisation précise du testicule non descendu et l'évaluation de la perfusion testiculaire et peut être une alternative utile à l'échographie pour diagnostiquer la torsion testiculaire, en particulier dans les cas indéterminés.(Traduit par Dr Serge Messier).
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Criptorquidismo , Enfermedades de los Perros , Torsión del Cordón Espermático , Animales , Criptorquidismo/diagnóstico por imagen , Criptorquidismo/cirugía , Criptorquidismo/veterinaria , Enfermedades de los Perros/diagnóstico por imagen , Enfermedades de los Perros/cirugía , Perros , Masculino , Torsión del Cordón Espermático/diagnóstico por imagen , Torsión del Cordón Espermático/cirugía , Torsión del Cordón Espermático/veterinaria , Tomografía Computarizada por Rayos X , Ultrasonografía/veterinariaRESUMEN
OBJECTIVE: To describe a technique for anastomosis of the thoracic duct (TD) to the 11th or 12th intercostal vein (ICV) using a microvascular anastomotic coupler (MAC) in the dog. STUDY DESIGN: Cadaveric study. ANIMALS: Eight beagles. METHODS: A right paracostal laparotomy and 10th intercostal thoracotomy were performed in each dog. Mesenteric contrast lymphography was used to identify the TD and its branches on fluoroscopy. The TD and adjacent 11th or 12th ICV were isolated, double ligated, and divided using a surgical microscope. The caudal TD and proximal ICV were anastomosed in an end-to-end fashion using a 1.5 mm or 2 mm MAC. Mesenteric lymphography was repeated to document patency of the anastomosis. RESULTS: The TD was identified via lymphography in all dogs; five dogs had a single duct, and three dogs had additional branches. The anastomosis was successful in all eight dogs, and flow into the azygos vein without leakage was confirmed via lymphography. CONCLUSION: End-to-end anastomosis of the TD to an ICV using a MAC was technically feasible in the canine cadaver. CLINICAL SIGNIFICANCE: Lymphaticovenous anastomosis combined with TD ligation may have application as a treatment for idiopathic chylothorax. By maintaining the flow of chyle from the abdominal lymphatics to the systemic circulation, this procedure may reduce the stimulus for collateral circulation and persistent flow to the cranial mediastinal lymphatics.
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Anastomosis Quirúrgica/veterinaria , Quilotórax/veterinaria , Enfermedades de los Perros/cirugía , Linfografía/veterinaria , Conducto Torácico/cirugía , Anastomosis Quirúrgica/métodos , Animales , Cadáver , Quilotórax/cirugía , PerrosRESUMEN
Clinical signs of liver lobe torsion in rabbits are often nonspecific and mimic those that are also generally detected with gastrointestinal stasis. Nonspecific clinical signs may result in pursuit of full-body imaging such as computed tomography (CT). The aim of this multicenter, retrospective, case series study was to describe CT findings of liver lobe torsion in a group of rabbits. Computed tomography studies of six rabbits with confirmed liver lobe torsion by surgery or necropsy were evaluated. The caudate liver lobe was affected in six out of six rabbits and was enlarged, rounded, hypoattenuating, heterogeneous, and minimally to noncontrast enhancing, with scant regional peritoneal effusion. Precontrast, mean Hounsfield units (HU) of the torsed liver lobe (39.3 HU [range, 24.4-48.1 HU]) were lower than mean HU of normal liver (55.1 HU [range, 49.6-60.8 HU]), with a mean torsed:normal HU ratio of 0.71 (range, 0.49-0.91). Postcontrast, mean HU of the torsed liver lobe (38.4 HU [range, 19.7-48.9 HU]) were also lower than mean HU of normal liver (108.4 HU [range, 84.5-142.0 HU]), with a lower postcontrast mean torsed:normal HU ratio of 0.35 (range, 0.14-0.48) compared to precontrast. Mean HU of torsed liver lobes had little difference pre- and postcontrast (postcontrast HU 1.0 times the average precontrast HU [range, 0.81-1.1]), and contrast enhancement of the torsed liver lobes was on average 50% lower than in normal liver. Liver lobe torsion should be considered in rabbits with an enlarged, hypoattenuating, heterogeneous, minimally to noncontrast enhancing liver lobe, particularly the caudate lobe, and scant regional peritoneal effusion.
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Hepatopatías/veterinaria , Tomografía Computarizada por Rayos X/veterinaria , Anomalía Torsional/veterinaria , Animales , Femenino , Hígado/patología , Hepatopatías/diagnóstico por imagen , Hepatopatías/patología , Masculino , Conejos , Estudios Retrospectivos , Anomalía Torsional/diagnóstico por imagenRESUMEN
18F-Fluoro-deoxyglucose positron emission computed tomography (FDG-PET/CT) is an emerging diagnostic imaging modality in veterinary medicine; however, little published information is available on physiologic variants, benign processes, and artifacts. The purpose of this retrospective study was to describe the number of occurrences of non-neoplastic disease-related FDG-PET/CT lesions in a group of dogs and cats. Archived FDG-PET/CT scans were retrieved and interpreted based on a consensus opinion of two board-certified veterinary radiologists. Non-neoplastic disease-related lesions were categorized as physiologic variant, benign activity, or equipment/technology related artifact. If the exact cause of hypermetabolic areas could not be determined, lesions were put into an indeterminate category. A total of 106 canine and feline FDG-PET/CT scans were included in the study. In 104 of the 106 scans, a total of 718 occurrences of physiologic variant, areas of incidental benign activity, and artifacts were identified. Twenty-two of 23 feline scans and 82 of 83 canine scans had at least one artifact. Previously unreported areas of increased radiopharmaceutical uptake included foci associated with the canine gall bladder, linear uptake along the canine mandible, and focal uptake in the gastrointestinal tract. Benign activity was often seen and related to healing, inflammation, and indwelling implants. Artifacts were most often related to injection or misregistration. Further experience in recognizing the common veterinary FDG physiologic variation, incidental radiopharmaceutical uptake, and artifacts is important to avoid misinterpretation and false-positive diagnoses.
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Artefactos , Gatos , Perros , Tomografía de Emisión de Positrones/veterinaria , Animales , Colorado , Fluorodesoxiglucosa F18 , Incidencia , Tomografía de Emisión de Positrones/normas , Radiofármacos , Estudios RetrospectivosRESUMEN
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.
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OBJECTIVE: This retrospective study aimed to measure rabbit laryngotracheal dimensions at different locations on computed tomography (CT), assess the relationship of these measurements with rabbit body weight, determine the most common narrowest measurement and assess its relationship with endotracheal tube (ETT) size and body weight. ANIMALS: 66 adult domestic rabbits (Oryctolagus cuniculus) of different breeds and body weights. PROCEDURES: CT laryngotracheal luminal height, width, and cross-sectional area measurements were made at the rostral thyroid cartilage at the level of the arytenoids, caudal thyroid cartilage/rostral cricoid cartilage, caudal cricoid cartilage/cranial trachea, and trachea at the level of the fifth cervical vertebra. RESULTS: The data for every measurement of luminal airway dimensions revealed robust positive associations with body weight (P < .001). The narrowest laryngotracheal measurement was the width at the level of the caudal thyroid cartilage/rostral cricoid cartilage, and the smallest cross-sectional area was at the rostral thyroid cartilage at the level of the arytenoids. There was a strong association between body weight and the likelihood of appropriate ETT fit. To have at least an 80% chance of appropriate ETT fit with a 2.0, 2.5, and 3.0 mm ETT, the rabbits' weight predicted by the model (lower 95% confidence limit) were at least 2.99 (2.72) kg, 5.24 (4.65) kg, and 5.80 (5.21) kg, respectively. CLINICAL RELEVANCE: The laryngotracheal lumen was narrowest at the level of the caudal thyroid cartilage in rabbits, which indicates this location may be the limiting factor in determining ETT size in rabbits.
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Cartílago Tiroides , Tráquea , Conejos , Animales , Cartílago Tiroides/diagnóstico por imagen , Estudios Retrospectivos , Tráquea/diagnóstico por imagen , Tomografía Computarizada por Rayos X/veterinaria , Cartílago Cricoides/diagnóstico por imagen , Peso CorporalRESUMEN
Tarsal joint abnormalities have been observed in aged male mice on a C57BL background. This joint disease consists of calcaneal displacement, inflammation, and proliferation of cartilage and connective tissue, that can progress to ankylosis of the joint. While tarsal pathology has been described previously in C57BL/6N substrains, as well as in STR/ort and B10.BR strain, no current literature describes this disease occurring in C57BL/6J mice. More importantly the behavioral features that may result from such a change to the joint have yet to be evaluated. This condition was observed in older male mice of the C57BL/6J lineage, around the age of 20 weeks or older, at a frequency of 1% of the population. To assess potential phenotypic sequela, this study sought to evaluate body weight, frailty assessment, home cage wheel running, dynamic weight bearing, and mechanical allodynia with and without the presence of pain relief with morphine. Overall mice with tarsal injuries had significantly higher frailty scores (p< 0.05) and weighed less (p<0.01) compared to unaffected mice. Affected mice had greater overall touch sensitivity (p<0.05) and they placed more weight on their forelimbs (p<0.01) compared to their hind limbs. Lastly, when housed with a running wheel, affected mice ran for a shorter length of time (p<0.01) but tended to run a greater distance within the time they did run (p<0.01) compared to unaffected mice. When tested just after being given morphine, the affected mice performed more similarly to unaffected mice, suggesting there is a pain sensation to this disease process. This highlights the importance of further characterizing inbred mouse mutations, as they may impact research programs or specific study goals.
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Fragilidad , Actividad Motora , Ratones , Masculino , Animales , Ratones Endogámicos C57BL , Morfina , DolorRESUMEN
In collaboration with the American College of Veterinary Radiology.
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Radiología , Animales , Humanos , Radiografía , Estados UnidosRESUMEN
The recent emergence of SARS-CoV-2 Omicron variants possessing large numbers of mutations has raised concerns of decreased effectiveness of current vaccines, therapeutic monoclonal antibodies, and antiviral drugs for COVID-19 against these variants1,2. While the original Omicron lineage, BA.1, has become dominant in many countries, BA.2 has been detected in at least 67 countries and has become dominant in the Philippines, India, and Denmark. Here, we evaluated the replicative ability and pathogenicity of an authentic infectious BA.2 isolate in immunocompetent and human ACE2 (hACE2)-expressing mice and hamsters. In contrast to recent data with chimeric, recombinant SARS-CoV-2 strains expressing the spike proteins of BA.1 and BA.2 on an ancestral WK-521 backbone3, we observed similar infectivity and pathogenicity in mice and hamsters between BA.2 and BA.1, and less pathogenicity compared to early SARS-CoV-2 strains. We also observed a marked and significant reduction in the neutralizing activity of plasma from COVID-19 convalescent individuals and vaccine recipients against BA.2 compared to ancestral and Delta variant strains. In addition, we found that some therapeutic monoclonal antibodies (REGN10987/REGN10933, COV2-2196/COV2-2130, and S309) and antiviral drugs (molnupiravir, nirmatrelvir, and S-217622) can restrict viral infection in the respiratory organs of hamsters infected with BA.2. These findings suggest that the replication and pathogenicity of BA.2 is comparable to that of BA.1 in rodents and that several therapeutic monoclonal antibodies and antiviral compounds are effective against Omicron/BA.2 variants.
RESUMEN
CASE DESCRIPTION: A 3-year-old 17.5-kg (38.5-lb) mixed-breed dog was referred for evaluation because of nasal discharge, sneezing, and signs of nasal congestion of approximately 9 months' duration. A diagnosis of nasopharyngeal stenosis (NPS) was made prior to referral. CLINICAL FINDINGS: Sneezing, bilateral mucopurulent nasal discharge, reduced nasal airflow, stertor, and increased inspiratory effort were noted on physical examination. Results of serum biochemical analysis were within respective reference ranges. Review of CT images of the skull revealed findings consistent with severe bilateral partial osseous choanal atresia and NPS. Retrograde rhinoscopy confirmed membranous NPS. TREATMENT AND OUTCOME: A ventral rhinotomy was performed; communication between the pharynx and nasal passageway was reestablished by surgical debridement of the caudal border of the palatine bone and vomerine crest and groove, followed by dissection of the membranous NPS and reconstruction of the caudal part of the nasopharynx. A covered nasopharyngeal stent was placed in the newly established nasopharynx. The dog recovered uneventfully but was presented 3 weeks later with recurrent signs; diagnostic findings were consistent with stenosis rostral to the stent. The stenosis was treated with balloon dilation, and a second covered stent was placed rostral to and overlapping the first stent, spanning the stenotic region. Eleven months after this procedure, the dog was doing well. CLINICAL RELEVANCE: Results for this patient suggested that ventral rhinotomy and covered nasopharyngeal stent placement can be used successfully for the management of osseous choanal atresia in dogs; however, careful attention to preoperative planning and potential complications is necessary.
Asunto(s)
Atresia de las Coanas , Enfermedades de los Perros , Enfermedades Nasofaríngeas , Animales , Atresia de las Coanas/cirugía , Atresia de las Coanas/veterinaria , Constricción Patológica/cirugía , Constricción Patológica/veterinaria , Enfermedades de los Perros/cirugía , Perros , Endoscopía/veterinaria , Enfermedades Nasofaríngeas/cirugía , Enfermedades Nasofaríngeas/veterinaria , StentsRESUMEN
Despite the development and deployment of antibody and vaccine countermeasures, rapidly-spreading SARS-CoV-2 variants with mutations at key antigenic sites in the spike protein jeopardize their efficacy. The recent emergence of B.1.1.529, the Omicron variant1,2, which has more than 30 mutations in the spike protein, has raised concerns for escape from protection by vaccines and therapeutic antibodies. A key test for potential countermeasures against B.1.1.529 is their activity in pre-clinical rodent models of respiratory tract disease. Here, using the collaborative network of the SARS-CoV-2 Assessment of Viral Evolution (SAVE) program of the National Institute of Allergy and Infectious Diseases (NIAID), we evaluated the ability of multiple B.1.1.529 Omicron isolates to cause infection and disease in immunocompetent and human ACE2 (hACE2) expressing mice and hamsters. Despite modeling and binding data suggesting that B.1.1.529 spike can bind more avidly to murine ACE2, we observed attenuation of infection in 129, C57BL/6, and BALB/c mice as compared with previous SARS-CoV-2 variants, with limited weight loss and lower viral burden in the upper and lower respiratory tracts. Although K18-hACE2 transgenic mice sustained infection in the lungs, these animals did not lose weight. In wild-type and hACE2 transgenic hamsters, lung infection, clinical disease, and pathology with B.1.1.529 also were milder compared to historical isolates or other SARS-CoV-2 variants of concern. Overall, experiments from multiple independent laboratories of the SAVE/NIAID network with several different B.1.1.529 isolates demonstrate attenuated lung disease in rodents, which parallels preliminary human clinical data.