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1.
Artículo en Inglés | MEDLINE | ID: mdl-38757436

RESUMEN

A 14-month-old female spayed, small crossbred rabbit presented for assessment of a small, hard subcutaneous nodule in the right axilla. Serum biochemistry showed markedly increased serum ALP activity. A whole-body CT revealed an aggressive, monostotic osteolytic, and productive lesion within the left alveolar process of the maxilla, with erosion of the alveolar bone and secondary premolar depression. Innumerable metastatic osseous masses were present throughout the body, including cerebral, pulmonary, hepatic, subcutaneous, and skeletal muscular metastases. Postmortem findings confirmed widespread, metastatic osteosarcoma, with the primary lesion within the left maxilla.

2.
J Infect ; 88(3): 106116, 2024 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-38331329

RESUMEN

OBJECTIVE: The huge burden of inaccurate penicillin allergy labels (PALs) is an important driver of antimicrobial resistance. This is magnified by insufficient allergy specialists and lack of 'point-of-care' tests. We investigated the feasibility of non-allergy healthcare professionals (HCPs) delivering direct oral penicillin challenges (DPCs) for penicillin allergy de-labelling. METHODS: This prospective observational study was conducted in three hospitals in England across three settings (acute medical, pre-surgical and haematology-oncology). Patients with a PAL were screened and stratified as low risk/high risk. Low risk patients (non-immune mediated symptoms, benign rash, tolerated amoxicillin since and family history) underwent a DPC. RESULTS: N = 2257 PALs were screened, 1054 were eligible; 643 were approached, 373 declined, 270 consented and 259 risk stratified (low risk = 155; high risk = 104). One hundred and twenty-six low risk patients underwent DPC, 122 (96.8%) were de-labelled with no serious allergic reactions. Conversion rate from screening-to-consent was 12% [3.3% and 17.9% in acute and elective settings respectively; odds ratios for consent were 3.42 (p < 0.001) and 5.53 (p < 0.001) in haematology-oncology and pre-surgical setting respectively. Common reasons for failure to progress in the study included difficulty in reaching patients, clinical instability/medical reasons, lacking capacity to consent and psychological factors. INTERPRETATION: DPCs can be delivered by non-allergy HCPs. A high proportion of patients with PALs did not progress in the study pathway. Strategies to deliver DPC at optimal points of the care pathway are needed to enhance uptake. Elective settings offer greater opportunities than acute settings for DPC. The safety and simplicity of DPCs lends itself to adoption by healthcare systems beyond the UK, including in resource-limited settings.


Asunto(s)
Hipersensibilidad a las Drogas , Hipersensibilidad , Humanos , Penicilinas/efectos adversos , Antibacterianos/efectos adversos , Estudios de Factibilidad , Pruebas Cutáneas , Hipersensibilidad a las Drogas/diagnóstico , Atención a la Salud
3.
Br J Neurosurg ; : 1-8, 2023 Nov 09.
Artículo en Inglés | MEDLINE | ID: mdl-37943103

RESUMEN

BACKGROUND: Perioperative Visual Loss (POVL) is a devastating complication for patients undergoing spine surgery. Consent process for POVL amongst spine surgeons and anaesthetist remains variable. The aim of this study is to evaluate their practice and views about it. METHODS: Two similar questionnaires were distributed to members of the Society of British Neurological Surgeons (SBNS), British Association of Spine Surgeons (BASS), and Neuroanaesthsia and Critical Care Society (NACCS). RESULTS: A total of 271 responses were received (SBNS/BASS n = 149, NACCS n = 122). Fewer surgeons considered POVL as a material risk for patients compared to the anaesthetists (57.7 versus 79.7%). Outpatient/pre-assessment clinics were considered as the optimal setting for discussing POVL by the majority of the clinicians (81.2 and 93.4%). POVL should be discussed by both specialists according to 75% of the anaesthetists. Estimated incidence of POVL was considered to be higher by the anaesthetists (0.03-0.2% by 63% of the anaesthetist versus 0.0001-0.004% by 57% of the surgeons). Twenty-three surgeons and 10 anaesthetists had a patient who suffered from POVL, which led to a change of practice in most of them. This questionnaire will lead to a change in practice/consent to 18.1% of the surgeons and 23.5% of the anaesthetists. CONCLUSIONS: Most of the surgeons and anaesthetist feel that POVL is a material risk that ideally needs to be firstly discussed before the day of surgery, by both specialties. However, a significant number of clinicians have an opposite view. A national guidance from respective societies should encourage POVL to be discussed routinely.

4.
Vet Surg ; 52(2): 238-248, 2023 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-36273378

RESUMEN

OBJECTIVE: To evaluate the effect of conventional multilevel surgery (CMS) for brachycephalic obstructive airway syndrome (BOAS) on associated sliding hiatal hernia (SHH) and/or gastroesophageal reflux (GER). STUDY DESIGN: Prospective clinical trial. ANIMALS: Sixteen client-owned dogs with clinical signs consistent with BOAS and associated SHH and GER. METHODS: All dogs were treated with 1 or more components of CMS including soft palate resection, laryngeal ventriculectomy, and alaplasty. A standardized Dog Swallowing Assessment Tool (Dog SAT) questionnaire was completed by owners preoperatively and postoperatively. Videofluoroscopic swallow studies (VFSS) were used to evaluate esophageal motility, gastroesophageal reflux, and hiatal herniation preoperatively, and in a subset of dogs postoperatively. Upper gastrointestinal endoscopic studies were performed to document esophagitis and lower esophageal sphincter pathology. RESULTS: All dogs were discharged from the hospital. One dog experienced aspiration pneumonia immediately postoperatively. Owner-assigned clinical scores improved in scores related to regurgitation after eating and regurgitation (P = .012) during increased activity/exercise (P = .002) between preoperative and postoperative time points. However, no improvement was detected in masked assessment of preoperative and postoperative VFSS studies in terms of GER frequency (P = .46) or severity (P = .79), SHH frequency (P = .082) or severity (P = .34) scores. CONCLUSION: Owners of dogs treated with CMS perceived an improvement in clinical signs of SHH and GER that was not confirmed by VFSS studies. CLINICAL SIGNIFICANCE: Conventional multilevel surgery in dogs with BOAS does not appear to consistently resolve SHH and GER, although clinical signs may improve.


Asunto(s)
Obstrucción de las Vías Aéreas , Enfermedades de los Perros , Reflujo Gastroesofágico , Hernia Hiatal , Animales , Perros , Obstrucción de las Vías Aéreas/cirugía , Obstrucción de las Vías Aéreas/veterinaria , Enfermedades de los Perros/diagnóstico por imagen , Enfermedades de los Perros/epidemiología , Enfermedades de los Perros/cirugía , Reflujo Gastroesofágico/diagnóstico por imagen , Reflujo Gastroesofágico/epidemiología , Reflujo Gastroesofágico/veterinaria , Hernia Hiatal/diagnóstico por imagen , Hernia Hiatal/epidemiología , Hernia Hiatal/veterinaria , Estudios Prospectivos , Resultado del Tratamiento , Grabación de Cinta de Video , Fluoroscopía/métodos
5.
Sci Transl Med ; 15(685): eadd6383, 2023 03.
Artículo en Inglés | MEDLINE | ID: mdl-36454813

RESUMEN

The U.S. Food and Drug Administration only gave emergency use authorization of the BNT162b2 and mRNA-1273 SARS-CoV-2 vaccines for infants 6 months and older in June 2022. Yet questions regarding the durability of vaccine efficacy, especially against emerging variants, in this age group remain. We demonstrated previously that a two-dose regimen of stabilized prefusion Washington SARS-CoV-2 S-2P spike (S) protein encoded by mRNA encapsulated in lipid nanoparticles (mRNA-LNP) or purified S-2P mixed with 3M-052, a synthetic Toll-like receptor (TLR) 7/8 agonist, in a squalene emulsion (Protein+3M-052-SE) was safe and immunogenic in infant rhesus macaques. Here, we demonstrate that broadly neutralizing and spike-binding antibodies against variants of concern (VOCs), as well as T cell responses, persisted for 12 months. At 1 year, corresponding to human toddler age, we challenged vaccinated rhesus macaques and age-matched nonvaccinated controls intranasally and intratracheally with a high dose of heterologous SARS-CoV-2 B.1.617.2 (Delta). Seven of eight control rhesus macaques exhibited severe interstitial pneumonia and high virus replication in the upper and lower respiratory tract. In contrast, vaccinated rhesus macaques had faster viral clearance with mild to no pneumonia. Neutralizing and binding antibody responses to the B.1.617.2 variant at the day of challenge correlated with lung pathology and reduced virus replication. Overall, the Protein+3M-052-SE vaccine provided superior protection to the mRNA-LNP vaccine, emphasizing opportunities for optimization of current vaccine platforms. The observed efficacy of both vaccines 1 year after vaccination supports the implementation of an early-life SARS-CoV-2 vaccine.


Asunto(s)
COVID-19 , Vacunas Virales , Animales , Humanos , Lactante , SARS-CoV-2 , Vacunas contra la COVID-19 , Macaca mulatta , Vacuna BNT162 , Anticuerpos Antivirales , Anticuerpos Neutralizantes
6.
Immunohorizons ; 6(12): 851-863, 2022 12 01.
Artículo en Inglés | MEDLINE | ID: mdl-36547390

RESUMEN

The global spread of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and its associated coronavirus disease (COVID-19) has led to a pandemic of unprecedented scale. An intriguing feature of the infection is the minimal disease in most children, a demographic at higher risk for other respiratory viral diseases. To investigate age-dependent effects of SARS-CoV-2 pathogenesis, we inoculated two rhesus macaque monkey dam-infant pairs with SARS-CoV-2 and conducted virological and transcriptomic analyses of the respiratory tract and evaluated systemic cytokine and Ab responses. Viral RNA levels in all sampled mucosal secretions were comparable across dam-infant pairs in the respiratory tract. Despite comparable viral loads, adult macaques showed higher IL-6 in serum at day 1 postinfection whereas CXCL10 was induced in all animals. Both groups mounted neutralizing Ab responses, with infants showing a more rapid induction at day 7. Transcriptome analysis of tracheal airway cells isolated at day 14 postinfection revealed significant upregulation of multiple IFN-stimulated genes in infants compared with adults. In contrast, a profibrotic transcriptomic signature with genes associated with cilia structure and function, extracellular matrix composition and metabolism, coagulation, angiogenesis, and hypoxia was induced in adults compared with infants. Our study in rhesus macaque monkey dam-infant pairs suggests age-dependent differential airway responses to SARS-CoV-2 infection and describes a model that can be used to investigate SARS-CoV-2 pathogenesis between infants and adults.


Asunto(s)
COVID-19 , Animales , Macaca mulatta , Pulmón/patología , SARS-CoV-2 , Replicación Viral
7.
PLoS Pathog ; 18(4): e1009925, 2022 04.
Artículo en Inglés | MEDLINE | ID: mdl-35443018

RESUMEN

Early in the SARS-CoV-2 pandemic, there was a high level of optimism based on observational studies and small controlled trials that treating hospitalized patients with convalescent plasma from COVID-19 survivors (CCP) would be an important immunotherapy. However, as more data from controlled trials became available, the results became disappointing, with at best moderate evidence of efficacy when CCP with high titers of neutralizing antibodies was used early in infection. To better understand the potential therapeutic efficacy of CCP, and to further validate SARS-CoV-2 infection of macaques as a reliable animal model for testing such strategies, we inoculated 12 adult rhesus macaques with SARS-CoV-2 by intratracheal and intranasal routes. One day later, 8 animals were infused with pooled human CCP with a high titer of neutralizing antibodies (RVPN NT50 value of 3,003), while 4 control animals received normal human plasma. Animals were monitored for 7 days. Animals treated with CCP had detectable but low levels of antiviral antibodies after infusion. In comparison to the control animals, CCP-treated animals had similar levels of viral RNA in upper and lower respiratory tract secretions, similar detection of viral RNA in lung tissues by in situ hybridization, but lower amounts of infectious virus in the lungs. CCP-treated animals had a moderate, but statistically significant reduction in interstitial pneumonia, as measured by comprehensive lung histology. Thus overall, therapeutic benefits of CCP were marginal and inferior to results obtained earlier with monoclonal antibodies in this animal model. By highlighting strengths and weaknesses, data of this study can help to further optimize nonhuman primate models to provide proof-of-concept of intervention strategies, and guide the future use of convalescent plasma against SARS-CoV-2 and potentially other newly emerging respiratory viruses.


Asunto(s)
COVID-19 , SARS-CoV-2 , Animales , Anticuerpos Neutralizantes , Antivirales , COVID-19/terapia , Humanos , Inmunización Pasiva , Macaca mulatta , ARN Viral , Sueroterapia para COVID-19
8.
Front Vet Sci ; 9: 882505, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-35372549

RESUMEN

[This corrects the article DOI: 10.3389/fvets.2020.00241.].

9.
Microbiol Spectr ; 9(3): e0139721, 2021 12 22.
Artículo en Inglés | MEDLINE | ID: mdl-34817208

RESUMEN

Human clinical studies investigating use of convalescent plasma (CP) for treatment of coronavirus disease 2019 (COVID-19) have produced conflicting results. Outcomes in these studies may vary at least partly due to different timing of CP administration relative to symptom onset. The mechanisms of action of CP include neutralizing antibodies but may extend beyond virus neutralization to include normalization of blood clotting and dampening of inflammation. Unresolved questions include the minimum therapeutic titer in the CP units or CP recipient as well as the optimal timing of administration. Here, we show that treatment of macaques with CP within 24 h of infection does not reduce viral shedding in nasal or lung secretions compared to controls and does not detectably improve any clinical endpoint. We also demonstrate that CP administration does not impact viral sequence diversity in vivo, although the selection of a viral sequence variant in both macaques receiving normal human plasma was suggestive of immune pressure. Our results suggest that CP, administered to medium titers, has limited efficacy, even when given very early after infection. Our findings also contribute information important for the continued development of the nonhuman primate model of COVID-19. These results should inform interpretation of clinical studies of CP in addition to providing insights useful for developing other passive immunotherapies and vaccine strategies. IMPORTANCE Antiviral treatment options for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) remain very limited. One treatment that was explored beginning early in the pandemic (and that is likely to be tested early in future pandemics) is plasma collected from people who have recovered from coronavirus disease 2019 (COVID-19), known as convalescent plasma (CP). We tested if CP reduces viral shedding or disease in a nonhuman primate model. Our results demonstrate that administration of CP 1 day after SARS-CoV-2 infection had no significant impact on viral loads, clinical disease, or sequence diversity, although treatment with normal human plasma resulted in selection of a specific viral variant. Our results demonstrate that passive immunization with CP, even during early infection, provided no significant benefit in a nonhuman primate model of SARS-CoV-2 infection.


Asunto(s)
COVID-19/terapia , Inmunización Pasiva/métodos , SARS-CoV-2 , Animales , Anticuerpos Neutralizantes/inmunología , Anticuerpos Antivirales/sangre , Antivirales/uso terapéutico , COVID-19/inmunología , Modelos Animales de Enfermedad , Humanos , Inmunidad , Pulmón/patología , Macaca mulatta , Pandemias , Glicoproteína de la Espiga del Coronavirus/inmunología , Carga Viral , Replicación Viral
10.
Cell Rep ; 37(5): 109942, 2021 11 02.
Artículo en Inglés | MEDLINE | ID: mdl-34706272

RESUMEN

Anti-viral monoclonal antibody (mAb) treatments may provide immediate but short-term immunity from coronavirus disease 2019 (COVID-19) in high-risk populations, such as people with diabetes and the elderly; however, data on their efficacy in these populations are limited. We demonstrate that prophylactic mAb treatment blocks viral replication in both the upper and lower respiratory tracts in aged, type 2 diabetic rhesus macaques. mAb infusion dramatically curtails severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-mediated stimulation of interferon-induced chemokines and T cell activation, significantly reducing development of interstitial pneumonia. Furthermore, mAb infusion significantly dampens the greater than 3-fold increase in SARS-CoV-2-induced effector CD4 T cell influx into the cerebrospinal fluid. Our data show that neutralizing mAbs administered preventatively to high-risk populations may mitigate the adverse inflammatory consequences of SARS-CoV-2 exposure.


Asunto(s)
Anticuerpos Monoclonales/uso terapéutico , COVID-19/prevención & control , SARS-CoV-2/inmunología , Envejecimiento/inmunología , Animales , COVID-19/líquido cefalorraquídeo , COVID-19/complicaciones , COVID-19/inmunología , Complicaciones de la Diabetes/inmunología , Complicaciones de la Diabetes/virología , Diabetes Mellitus Experimental/complicaciones , Diabetes Mellitus Experimental/inmunología , Femenino , Humanos , Activación de Linfocitos , Macaca mulatta , Masculino , Neuritis/inmunología , Neuritis/prevención & control , Profilaxis Pre-Exposición , Linfocitos T/inmunología , Replicación Viral/inmunología
12.
bioRxiv ; 2021 Sep 01.
Artículo en Inglés | MEDLINE | ID: mdl-34494025

RESUMEN

Early in the SARS-CoV-2 pandemic, there was a high level of optimism based on observational studies and small controlled trials that treating hospitalized patients with convalescent plasma from COVID-19 survivors (CCP) would be an important immunotherapy. However, as more data from controlled trials became available, the results became disappointing, with at best moderate evidence of efficacy when CCP with high titers of neutralizing antibodies was used early in infection. To better understand the potential therapeutic efficacy of CCP, and to further validate SARS-CoV-2 infection of macaques as a reliable animal model for testing such strategies, we inoculated 12 adult rhesus macaques with SARS-CoV-2 by intratracheal and intranasal routes. One day later, 8 animals were infused with pooled human CCP with a high titer of neutralizing antibodies (RVPN NT 50 value of 3,003), while 4 control animals received normal human plasma. Animals were monitored for 7 days. Animals treated with CCP had detectable levels of antiviral antibodies after infusion. In comparison to the control animals, they had similar levels of virus replication in the upper and lower respiratory tract, but had significantly reduced interstitial pneumonia, as measured by comprehensive lung histology. By highlighting strengths and weaknesses, data of this study can help to further optimize nonhuman primate models to provide proof-of-concept of intervention strategies, and guide the future use of convalescent plasma against SARS-CoV-2 and potentially other newly emerging respiratory viruses. AUTHOR SUMMARY: The results of treating SARS-CoV-2 infected hospitalized patients with COVID-19 convalescent plasma (CCP), collected from survivors of natural infection, have been disappointing. The available data from various studies indicate at best moderate clinical benefits only when CCP with high titer of neutralizing antibodies was infused early in infection. The macaque model of SARS-CoV-2 infection can be useful to gain further insights in the value of CCP therapy. In this study, animals were infected with SARS-CoV-2 and the next day, were infused with pooled human convalescent plasma, selected to have a very high titer of neutralizing antibodies. While administration of CCP did not result in a detectable reduction in virus replication in the respiratory tract, it significantly reduced lung inflammation. These data, combined with the results of monoclonal antibody studies, emphasize the need to use products with high titers of neutralizing antibodies, and guide the future development of CCP-based therapies.

13.
PLoS Pathog ; 17(7): e1009688, 2021 07.
Artículo en Inglés | MEDLINE | ID: mdl-34228761

RESUMEN

There is an urgent need for effective therapeutic interventions against SARS-CoV-2, including new variants that continue to arise. Neutralizing monoclonal antibodies have shown promise in clinical studies. We investigated the therapeutic efficacy of a combination of two potent monoclonal antibodies, C135-LS and C144-LS that carry half-life extension mutations, in the rhesus macaque model of COVID-19. Twelve young adult macaques (three groups of four animals) were inoculated intranasally and intra-tracheally with a high dose of SARS-CoV-2 and 24 hours later, treated intravenously with a high (40 mg/kg) or low (12 mg/kg) dose of the C135-LS and C144-LS antibody combination, or a control monoclonal antibody. Animals were monitored for 7 days. Compared to the control animals, animals treated with either dose of the anti-SARS-CoV-2 antibodies showed similarly improved clinical scores, lower levels of virus replication in upper and lower respiratory tract, and significantly reduced interstitial pneumonia, as measured by comprehensive lung histology. In conclusion, this study provides proof-of-concept in support of further clinical development of these monoclonal antibodies against COVID-19 during early infection.


Asunto(s)
Anticuerpos Neutralizantes/uso terapéutico , Anticuerpos Antivirales/uso terapéutico , COVID-19/terapia , Pulmón/patología , SARS-CoV-2/inmunología , Replicación Viral , Animales , Anticuerpos Monoclonales/sangre , Anticuerpos Monoclonales/inmunología , Anticuerpos Monoclonales/uso terapéutico , Anticuerpos Neutralizantes/sangre , Anticuerpos Neutralizantes/inmunología , Anticuerpos Antivirales/sangre , Anticuerpos Antivirales/inmunología , COVID-19/patología , COVID-19/virología , Modelos Animales de Enfermedad , Femenino , Pulmón/diagnóstico por imagen , Macaca mulatta , Masculino , Análisis Multivariante , Radiografía , Sistema Respiratorio/virología , SARS-CoV-2/fisiología , Factores de Tiempo , Resultado del Tratamiento , Replicación Viral/inmunología
14.
Vet Surg ; 50 Suppl 1: O67-O77, 2021 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-33687078

RESUMEN

OBJECTIVE: To describe a laparoscopic technique for treatment of sliding hiatal hernia (SHH) and associated gastroesophageal reflux (GER) in brachycephalic dogs and document clinical and videofluoroscopic outcomes postoperatively. STUDY DESIGN: Prospective clinical trial. ANIMALS: Eighteen client-owned dogs. METHODS: A three-port laparoscopic approach was used. Intracorporeal suturing was used for hiatal plication and esophagopexy, and left-sided laparoscopic or laparoscopic-assisted gastropexy was performed. A standardized canine dysphagia assessment tool (CDAT) questionnaire was completed by owners pre- and postoperatively. Videofluoroscopic swallow studies (VFSS) were used to evaluate esophageal function, and impedance planimetry was used to assess lower esophageal sphincter geometry preoperatively and in a subset of dogs postoperatively. RESULTS: Median age was 27.5 (range 5-84) months. Conversion to open surgery was necessary in 1 (5.5%) of 18 dogs. Regurgitation after eating, and associated with activity/exercise, improved significantly when comparing pre- and postoperative CDAT assessments. Hiatal hernia and GER severity scores improved significantly between pre- and postoperative VFSS assessments, whereas SHH and GER frequency scores did not. One dog developed pneumothorax intraoperatively, underwent cardiopulmonary arrest, and died. Minor complications included splenic (n = 6) and hepatic lacerations (n = 3) that did not require specific therapy. CONCLUSION: A laparoscopic approach to treatment of SHH and GER led to improvements in clinical and VFSS indices in the majority of brachycephalic dogs. However, a subset of dogs still demonstrated some clinical signs postoperatively. CLINICAL RELEVANCE: In experienced hands, laparoscopic treatment of SHH and GER offers a minimally invasive alternative to open surgery.


Asunto(s)
Enfermedades de los Perros , Reflujo Gastroesofágico , Hernia Hiatal , Laparoscopía , Animales , Enfermedades de los Perros/cirugía , Perros , Esfínter Esofágico Inferior/diagnóstico por imagen , Esfínter Esofágico Inferior/cirugía , Reflujo Gastroesofágico/diagnóstico por imagen , Reflujo Gastroesofágico/etiología , Reflujo Gastroesofágico/cirugía , Reflujo Gastroesofágico/veterinaria , Hernia Hiatal/diagnóstico por imagen , Hernia Hiatal/cirugía , Hernia Hiatal/veterinaria , Laparoscopía/veterinaria , Estudios Prospectivos
15.
Vet Radiol Ultrasound ; 62(3): 271-281, 2021 May.
Artículo en Inglés | MEDLINE | ID: mdl-33439529

RESUMEN

Radiographic assessment of heart size is important for clinical management of dogs with cardiovascular disease (CVDz). We sought to compare the ability of vertebral heart size (VHS), vertebral left atrial size (VLAS), and radiologists' assessment of left atrial size (RadLAE) to predict echocardiographic left atrial size (EchoLAE), an important marker of left heart disease severity. We also compared the ability of VHS and VLAS to predict echocardiographic criteria for ACVIM stage B2 (EchoB2) in dogs with myxomatous mitral valve disease (MMVD). This prospective observational study enrolled 183 dogs with known or suspected CVDz that had an echocardiographic examination and thoracic radiographs obtained within 24 h. Compared to increased VHS, VLAS >2.3 was a more accurate predictor of EchoLAE (P = .002). VLAS >2.3 and RadLAE (both P <.0001) were independently associated with EchoLAE but VHS was not (P = .45). Optimal cutoffs for VLAS and VHS to predict EchoLAE were >2.3 vertebrae (sensitivity [Sn] = 90.3%, specificity [Sp] = 73.6%) and >11.1 vertebrae (Sn = 75.8%, Sp = 76.0%), respectively. Diagnostic accuracy of VLAS (AUC 0.84, 95% CI 0.73-0.92) and VHS (AUC 0.78, 95% CI 0.66-0.88) to predict EchoB2 in dogs with subclinical MMVD (n = 64) were not significantly different (P = .17). Results demonstrate that VLAS and RadLAE were superior indicators of EchoLAE compared to VHS in dogs with known or suspected CVDz. Both VLAS and VHS are useful predictors of EchoB2 in dogs with subclinical MMVD. When echocardiography is unavailable, VLAS represents a useful radiographic measurement to aid clinical management of dogs with known or suspected CVDz.


Asunto(s)
Cardiomegalia/veterinaria , Enfermedades de los Perros/diagnóstico por imagen , Animales , Cardiomegalia/diagnóstico por imagen , Perros , Ecocardiografía/veterinaria , Enfermedades de las Válvulas Cardíacas/veterinaria , Masculino , Estudios Prospectivos
16.
ACS Biomater Sci Eng ; 6(12): 6886-6895, 2020 12 14.
Artículo en Inglés | MEDLINE | ID: mdl-33320598

RESUMEN

Detection of slight changes in the chemical, thermal, and physical environments of the ocular surface is necessary to protect eyesight. The cornea, as the most densely innervated peripheral tissue in the body, can be damaged as a result of caustic chemical exposure. Such damage can be painful and debilitating, thus underscoring the need to understand mechanisms of ocular irritation. Both ethical and translational limitations regarding the use of animal subjects in part drive the need to develop relevant in vitro cell and tissue models that emulate the physiology of the human cornea. In this study, we utilized our 3D in vitro cornea-like tissue model to study the effects of irritation mediated by transient receptor potential (TRP) channels vanilloid 1 and ankyrin 1 (TRPV1; TRPA1) in response to allyl isothiocyanate (AITC) stimulation. Changes in gene expression were analyzed to characterize wound healing responses of the epithelial, stromal, and neuronal cell populations in the corneal tissue models. Key findings of the study include indications of wound healing, such as stromal myofibroblast differentiation and epithelial barrier re-establishment, amplification of pro-inflammatory cytokines, and downstream ECM protein remodeling due to irritation with the addition of sensory innervation. This study further establishes this in vitro tissue model as a useful tool for studying corneal irritation in vitro in a holistic manner with promise as a novel and sensitive tool for studying chemical exposures and subsequent responses.


Asunto(s)
Córnea , Inflamación , Animales , Humanos , Inflamación/inducido químicamente , Neuronas , Dolor , Cicatrización de Heridas
17.
Chiropr Man Therap ; 28(1): 56, 2020 11 13.
Artículo en Inglés | MEDLINE | ID: mdl-33183329

RESUMEN

BACKGROUND: This paper presents a case of an evolving unusual thunderclap headache that presented to a chiropractor. CASE PRESENTATION: The intense "migraine-like" headache was aggravated by standing up and relieved substantially when lying down. This low pressure, orthostatic headache was diagnosed as a spontaneous intracranial hypotension (SIH) secondary to a spontaneous tear of the dura. It was referred to the local hospital for management with autogolous blood injection to form an epidural blood patch of the defect. It resolved substantially within 3 days. CONCLUSIONS: The significance of key features in the history and examination and how if not recognised and subsequently treated with manual therapy, the dural tear could be attributed to the treatment of the chiropractor, a treatment that would typically involve cervical manipulation. Discussion is provided of the implications of a missed diagnosis and possible subsequent chiropractic management with the evolving SIH being attributed to the chiropractic intervention rather than its true "spontaneous" nature.


Asunto(s)
Cefalea/diagnóstico , Hipotensión Intracraneal/diagnóstico , Cefalea/terapia , Humanos , Hipotensión Intracraneal/terapia , Masculino , Adulto Joven
18.
Front Vet Sci ; 7: 242, 2020.
Artículo en Inglés | MEDLINE | ID: mdl-32478108

RESUMEN

Treatment of craniomaxillofacial (CMF) trauma in dogs requires a thorough understanding of the CMF skeletal structures involved. The human medical literature has several examples of CMF trauma and fracture classification, including the classically described Le Fort fractures. The recent classification schemes require large studies using computed tomography (CT). In the veterinary medical literature, such studies are lacking. The aims of part II of this retrospective study were to use a large number of CT studies of dogs evaluated for CMF trauma to determine whether specific fracture locations in the CMF region occur concurrently, and whether trauma etiology influences fracture morphology. This information may then be used to form a fracture classification scheme in the future. The medical records and CT studies of 165 dogs over a 10-year period were evaluated. The skeletal location of CMF fractures as well as the severity of displacement and fragmentation of each fracture was recorded. Dogs' demographic data and trauma etiology were also recorded. Fractured portions of the mandible tended to occur with fractures of adjacent bones, with the major exception of symphyseal separation, which occurred simultaneously with fractures of the cribriform plate. Fractures of the maxillary bone were accompanied by many concurrent fractures affecting the majority of the midface, skull base, and cranial vault. When the zygomatic bone was fractured, the other bones comprising the orbit also tended to fracture. Fractures of the relatively superficially located frontal and nasal bones were often accompanied by fractures of the skull base. Fracture etiology influenced fracture morphology such that vehicular trauma resulted in a relatively higher number of severely displaced and comminuted fractures than did other trauma etiologies. This study provides examples of fractures that, when found, should prompt veterinarians to look for additional injuries in specific locations. In addition, it further highlights the need for thorough CT evaluation of the entire CMF region, even when clinically apparent fractures appear relatively superficial.

19.
Front Vet Sci ; 7: 241, 2020.
Artículo en Inglés | MEDLINE | ID: mdl-32411743

RESUMEN

Treatment of craniomaxillofacial (CMF) trauma in dogs often requires a multidisciplinary approach and a thorough understanding of the CMF skeletal structures involved. The aim of this retrospective study was to use a large number of CT studies of dogs evaluated for CMF trauma and to describe fracture location and morphology in relation to demographic data and trauma etiology. The medical records and CT studies of 165 dogs over a 10-year period were evaluated. The skeletal location of CMF fractures as well as the severity of displacement and fragmentation of each fracture was recorded. Patient demographic data and trauma etiology were also recorded. Animal bites accounted for the majority of trauma (50%), followed by unknown trauma (15%), vehicular accidents (13%), and blunt force trauma (13%). Small dogs, <10 kg, and juveniles accounted for the majority of patients (41.8 and 25.5%, respectively). The most likely bone or region to be fractured was the maxillary bone, followed by the premolar and molar regions of the mandible. Up to 37 bones or regions were fractured in any given patient, with an average of 8.2 fractured bones or regions per dog. The most commonly fractured location varied according to trauma etiology. Specifically, vehicular accidents tended to result in more locations with a higher probability of fracture than other trauma types. A major conclusion from this study is that every bone of the CMF region was fractured in at least one case and many cases had a large number of fractured regions. Thus, the need for comprehensive assessment of the entire CMF region, preferably using CT, is underscored.

20.
Syst Rev ; 9(1): 91, 2020 04 24.
Artículo en Inglés | MEDLINE | ID: mdl-32331530

RESUMEN

BACKGROUND: The importance of teaching the skills and practice of evidence-based medicine (EBM) for medical professionals has steadily grown in recent years. Alongside this growth is a need to evaluate the effectiveness of EBM curriculum as assessed by competency in the five 'A's': asking, acquiring, appraising, applying and assessing (impact and performance). EBM educators in medical education will benefit from a compendium of existing assessment tools for assessing EBM competencies in their settings. The purpose of this review is to provide a systematic review and taxonomy of validated tools that evaluate EBM teaching in medical education. METHODS: We searched MEDLINE, EMBASE, Cochrane library, Educational Resources Information Centre (ERIC), Best Evidence Medical Education (BEME) databases and references of retrieved articles published between January 2005 and March 2019. We have presented the identified tools along with their psychometric properties including validity, reliability and relevance to the five domains of EBM practice and dimensions of EBM learning. We also assessed the quality of the tools to identify high quality tools as those supported by established interrater reliability (if applicable), objective (non-self-reported) outcome measures and achieved ≥ 3 types of established validity evidence. We have reported our study in accordance with the PRISMA guidelines. RESULTS: We identified 1719 potentially relevant articles of which 63 full text articles were assessed for eligibility against inclusion and exclusion criteria. Twelve articles each with a unique and newly identified tool were included in the final analysis. Of the twelve tools, all of them assessed the third step of EBM practice (appraise) and four assessed just that one step. None of the twelve tools assessed the last step of EBM practice (assess). Of the seven domains of EBM learning, ten tools assessed knowledge gain, nine assessed skills and-one assessed attitude. None addressed reaction to EBM teaching, self-efficacy, behaviours or patient benefit. Of the twelve tools identified, six were high quality. We have also provided a taxonomy of tools using the CREATE framework, for EBM teachers in medical education. CONCLUSIONS: Six tools of reasonable validity are available for evaluating most steps of EBM and some domains of EBM learning. Further development and validation of tools that evaluate all the steps in EBM and all educational outcome domains are needed. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42018116203.


Asunto(s)
Educación Médica , Competencia Clínica , Curriculum , Medicina Basada en la Evidencia , Humanos , Aprendizaje , Reproducibilidad de los Resultados , Enseñanza
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