Publications by authors named "Thomas J Divers"

96 Publications

The pathophysiology of uncontrolled hemorrhage in horses.

J Vet Emerg Crit Care (San Antonio) 2022 Jan;32(S1):63-71

Department of Clinical Sciences, College of Veterinary Medicine, Cornell University, Ithaca, New York, USA.

Background: Hemorrhagic shock in horses may be classified in several ways. Hemorrhage may be considered internal versus external, controlled or uncontrolled, or described based on the severity of hypovolemic shock the patient is experiencing. Regardless of the cause, as the severity of hemorrhage worsens, homeostatic responses are stimulated to ameliorate the systemic and local effects of an oxygen debt. In mild to moderate cases of hemorrhage (<15% blood volume loss), physiological adaptations in the patient may not be clinically apparent. As hemorrhage worsens, often in the uncontrolled situation such as a vascular breach internally, the pathophysiological consequences are numerous. The patient mobilizes fluid and reserve blood volume, notably splenic stored and peripherally circulating erythrocytes, to preferentially supply oxygen to sensitive organs such as the brain and heart. When the global and local delivery of oxygen is insufficient to meet the metabolic needs of the tissues, a cascade of cellular, tissue, and organ dysfunction occurs. If left untreated, the patient dies of hemorrhagic anemic shock.

Clinical Importance: An understanding of the pathophysiological consequences of hemorrhagic shock in horses and their clinical manifestations may help the practitioner understand the severity of blood volume loss, the need for referral, the need for transfusion, and potential outcome. In cases of severe acute uncontrolled hemorrhage, it is essential to recognize the clinical manifestations quickly to best treat the patient, which may include humane euthanasia.

Key Points: Uncontrolled hemorrhage may be defined as the development of a vascular breach and hemorrhage that cannot be controlled by interventional hemostasis methods such as external pressure, tourniquet, or ligation. Causes of uncontrolled hemorrhage in horses may be due to non-surgical trauma, surgical trauma, invasive diagnostic procedures including percutaneous organ biopsy, coagulopathy, hypertension, cardiovascular anomaly, vascular damage, neoplasia such as hemangiosarcoma, toxicity, or idiopathic in nature. When a critical volume of blood is lost, the respondent changes in heart rate, splenic blood mobilization, and microcirculatory control can no longer compensate for decreasing oxygen delivery to the tissues In spite of organ-specific microvascular responses (eg, myogenic responses, local mediator modulation of microvasculature, etc), all organs experience decreases in blood flow during severe hypovolemia Acute, fatal hemorrhagic shock is characterized by progressive metabolic acidosis, coagulopathy, and hypothermia, often termed the "triad of death," followed by circulatory collapse.
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http://dx.doi.org/10.1111/vec.13122DOI Listing
January 2022

Collection and administration of blood products in horses: Transfusion indications, materials, methods, complications, donor selection, and blood testing.

J Vet Emerg Crit Care (San Antonio) 2022 Jan;32(S1):108-122

Department of Clinical Sciences, College of Veterinary Medicine, Cornell University, Ithaca, New York, USA.

Background: Blood transfusion is a lifesaving treatment for horses with acute hemorrhage and other causes of anemia. Transfusions improve oxygen delivery to the tissues via increased blood volume and hemoglobin concentration. Certain aspects of equine blood transfusion are challenging, especially in the field situation, and practitioners may be unfamiliar or feel overwhelmed with the process. An understanding of the indications, materials, methods, and techniques as well as donor selection and possible complications will help practitioners successfully implement blood transfusion in clinical practice.

Procedures: Blood transfusion involves several steps including appropriate donor selection, cross-matching, blood collection, and administration, as well as monitoring and handling of transfusion reactions. Guidance for each of these steps are detailed in this review.

Summary: Blood transfusion is an effective and often lifesaving treatment for managing diseases of blood loss, hemolysis, and decreased RBC production. Equine practitioners require a thorough understanding of the indications for blood transfusion, the immunological principles behind compatibility testing and transfusion reactions, and the technical skills to aseptically collect and administer blood products KEY POINTS: Equine practitioners require a thorough understanding of the indications for blood transfusion, the immunological principles behind compatibility testing and transfusion reactions, and the technical skills to aseptically collect and administer blood products. Because there are over 400,000 possible equine RBC phenotypes, no universal donor exists, and some blood type incompatibilities are likely between any donor and recipient. Therefore, prior to any blood transfusion, donor and recipient blood should be cross-matched Inadequate delivery of oxygen (Do ) to the tissues, resulting from low hemoglobin (Hb) concentration, is the most important indication for blood transfusion Neonatal isoerythrolysis most commonly occurs following an anamnestic response in late gestation; it rarely occurs following a primary exposure because the immune response is not strong enough to produce clinically significant alloantibody titers.
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http://dx.doi.org/10.1111/vec.13119DOI Listing
January 2022

Abdominocentesis techniques in horses.

J Vet Emerg Crit Care (San Antonio) 2022 Jan;32(S1):72-80

Department of Clinical Sciences, College of Veterinary Medicine, Cornell University, Ithaca, New York, USA.

Background: Abdominocentesis is commonly used to evaluate the abdominal cavity of the horse. This technique provides valuable diagnostic information as well as the means to monitor patients with abdominal diseases being managed medically and to determine their need for surgical management. Complications are uncommon and include trauma to the gastrointestinal tract or spleen, septic peritonitis, or abdominal wall infection.

Procedures: This review describes the indications, utility, patient preparation, and instructions for performing abdominocentesis as well as possible complications reported in horses. Step-by-step instructions are provided for the two most commonly used abdominocentesis techniques in horses, which include the use of a needle (18 Ga, 3.8 cm [1.5 in]) and a teat cannula (9.5 cm [3.75 in]).

Summary: Peritoneal fluid collection and fluid analysis can be used to confirm diagnosis of intraabdominal pathology including inflammatory, infectious, neoplastic, obstructive, and bowel strangulation, leading to additional diagnostic and therapeutic plans.

Key Points: Abdominocentesis is useful as a diagnostic procedure in horses suffering from colic, diarrhea, weight loss, or other conditions involving the abdominal cavity and is an integral component of diagnostic testing for colic at referral institutions or in the field. Abdominal fluid collection using an 18-Ga, 3.8-cm (1.5-in) needle is recommended for adult horses because the needle is long enough to penetrate the peritoneal cavity. The teat cannula technique is recommended for use in adult horses, foals, and miniature horses to reduce the risk of enterocentesis, even though this procedure is more traumatic than using an 18-Ga, 3.8-cm needle. Ultrasonography of the abdomen is a valuable tool in the assessment of any horse with signs of colic, but it is not essential for performing an abdominocentesis successfully.
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http://dx.doi.org/10.1111/vec.13118DOI Listing
January 2022

Interpreting abdominal fluid in colic horses: Understanding and applying peritoneal fluid evidence.

J Vet Emerg Crit Care (San Antonio) 2022 Jan;32(S1):81-96

Department of Clinical Sciences, College of Veterinary Medicine, Cornell University, Ithaca, New York, USA.

Background: Interpreting changes in peritoneal fluid helps clinicians manage colic and other diseases in horses. During abdominal problems in the horse, abdominal fluid characteristics such as color, turbidity, total nucleated and red blood cell counts, cytology, total protein, and l-lactate change in predictable ways, helping the clinician characterize the disease.

Description: Normal abdominal fluid in horses is odorless, clear to light yellow in color, and transparent. Peritoneal fluid becomes more turbid with increasing levels of protein, number of WBCs or RBCs, or with gross contamination following intestinal rupture. The color of abdominal fluid will also change with the type and quantity of cells or other elements present. The transformation of peritoneal fluid color from golden to orange to red represents increasing levels of RBCs, common with strangulating intestinal lesions. Serosanguinous defines fluid that is both turbid and orange to bloody because of increased total protein, WBCs, and RBCs, and is considered classic for diseases characterized by intestinal ischemia. Peritoneal fluid may also be red or blood-colored because of a hemoperitoneum, or secondary to blood contamination during sample collection. l-Lactate measurement in the abdominal fluid has proven invaluable for the identification of strangulating intestinal injury. Cytology acts as an important supplement to cell counts in peritoneal fluid, and the normal ratio of non-degenerate neutrophils:mononuclear cells of 2:1 changes during various gastrointestinal diseases. Culture of peritoneal fluid samples should be performed when septic peritonitis is suspected.

Summary: Abdominal fluid is a sensitive indicator of intestinal injury and a useful tool to direct treatment. Peritoneal fluid evaluation includes gross visual and olfactory examination, nucleated cell count, total protein, RBC count, lactate levels, cytology, and culture. The changes noted in such variables are related to the type and duration of the abdominal problem.

Key Points:  Abdominal fluid interpretation has become central to the triage and management of challenging equine colic patients.  The transformation of peritoneal fluid color from golden to orange to red represents increasing levels of RBCs, common with strangulating intestinal lesions.  Contamination with RBCs at various concentrations may be secondary to vascular (eg, abdominal wall or mesenteric vessels) or splenic trauma during abdominal fluid collection; however, this must be distinguished from orange to red fluid associated with intestinal strangulating obstruction or hemoabdomen  Peritoneal fluid analysis reveals abdominal pathology by recognizing specific changes that occur with disease processes affecting the tissues and organs within this cavity.  Abdominal fluid examination should be used as a tool to direct treatment rather than the definitive test for diagnosis of the acute abdomen  Septic peritonitis in horses most commonly originates secondary to intestinal compromise or accidents (vascular damage, perforation, or surgical manipulation), leading to bacterial translocation into the abdomen.
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http://dx.doi.org/10.1111/vec.13117DOI Listing
January 2022

Calculating and selecting fluid therapy and blood product replacements for horses with acute hemorrhage.

J Vet Emerg Crit Care (San Antonio) 2022 Jan;32(S1):97-107

Emergency Surgery and Medicine, Cornell Ruffian Equine Specialists, Elmont, New York, USA.

Background: Blood products, crystalloids, and colloid fluids are used in the medical treatment of severe hemorrhage in horses with a goal of providing sufficient blood flow and oxygen delivery to vital organs. The fluid treatments for hemorrhage will vary depending upon severity and duration and whether hemorrhage is controlled or uncontrolled.

Description: With acute and severe controlled hemorrhage, treatment is focused on rapidly increasing perfusion pressure and blood flow to vital organs. This can most easily be accomplished in field cases by the administration of hypertonic saline. If isotonic crystalloids are used for resuscitation, the volume administered should be at least as great as the estimated blood loss. Following crystalloid resuscitation, clinical signs, HCT, and laboratory evidence of tissue hypoxia may help determine the need for a whole blood transfusion. In uncontrolled hemorrhage, crystalloid resuscitation is often more conservative and is referred to as "permissive hypotension." The goal of "permissive hypotension" would be to provide enough perfusion pressure to vital organs such that function is maintained while keeping blood pressure below the normal range in the hope that clot formation will not be disrupted. Whole blood and fresh frozen plasma in addition to aminocaproic acid are indicated in most horses with severe uncontrolled hemorrhage.

Summary: Blood transfusion is a life-saving treatment for severe hemorrhage in horses. No precise HCT serves as a transfusion trigger; however, an HCT < 15%, lack of appropriate clinical response, or significant improvement in plasma lactate following crystalloid resuscitation and loss of 25% or more of blood volume is suggestive of the need for whole blood transfusion. Mathematical formulas may be used to estimate the amount of blood required for transfusion following severe but controlled hemorrhage, but these are not very accurate and, in practice, transfusion volume should be approximately 40% of estimated blood loss.

Key Points: Modest hemorrhage, <15% of blood volume (<12 mL/kg), can be fully compensated by physiological mechanisms and generally does not require fluid or blood product therapy. More severe hemorrhage, >25% of blood volume (> 20 mL/kg), often requires crystalloid or blood product replacement, while acute loss of greater than 30% (>24 mL/kg) of blood volume may result in hemorrhagic shock requiring resuscitation treatments Uncontrolled hemorrhage is a common occurrence in equine practice, and is most commonly associated with abdominal bleeding (eg, uterine artery rupture in mares). If the hemorrhage can be controlled such as by ligation of a bleeding vessel, then initial efforts to resuscitate the horse should focus on increasing perfusion pressure and blood flow to organs as quickly as possible with crystalloids or colloids while assessing need for whole blood transfusion. While fluid therapy is being administered every effort to physically control hemorrhage should be made using ligatures, application of compression, surgical methods, and local hemostatic agents like collagen-, gelatin-, and cellulose-based products, fibrin, yunnan baiyao (YB), and synthetic glues Although some synthetic colloids have been shown to be associated with acute kidney injury in people receiving resuscitation therapy, this undesirable effect in horses has not been reported.
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http://dx.doi.org/10.1111/vec.13127DOI Listing
January 2022

Bile Acids, Direct Bilirubin and Gamma-glutamyltransferase as Prognostic Indicators for Horses with Liver Disease in the Eastern United States: 82 Cases (1997-2019).

J Equine Vet Sci 2021 10 16;105:103729. Epub 2021 Aug 16.

Department of Clinical Sciences, College of Veterinary Medicine, Cornell University, Ithaca, New York, 14853.

Serum biochemistry results and presence of fibrosis on liver biopsies are frequently used as prognostic indicators in horses with liver dysfunction. The objective of this retrospective multicenter study was to determine if the magnitude of abnormal liver specific biochemical tests such as bile acids (BA), direct bilirubin and gamma-glutamyltransferase (GGT), or the presence of fibrosis reported on liver biopsies was associated with prognosis in horses with liver dysfunction. Eighty-two horses older than one year, examined at four referral hospitals in the eastern United States, with BA values greater than 30 µmol/L and having 6-months or more follow-up were included in the study. The association of the maximal BA, GGT and direct bilirubin values of each horse with survival was determined by logistic regression analysis. The presence or absence of fibrosis (non-quantitated) on a liver biopsy was compared between survivors and non-survivors by chi square test. The degree of increase in BA concentration and GGT activity was not related to outcome (OR 0.9999, 95% CI 0.9923 - 1.007, P = 0.97, and OR 1.0, 95% CI 0.9997 - 1.001, P = 0.31 respectively). Direct bilirubin concentration was positively associated with non-survival (OR 1.95, 95% CI 1.34-3.19, P = 0.0023). The presence of fibrosis was not associated with outcome (P = 0.37). These findings suggest that the magnitude of GGT and BA values or the mere presence of fibrosis on liver histopathology should not be used as prognostic indicators. In this study, direct bilirubin values were a better predictor of outcome.
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http://dx.doi.org/10.1016/j.jevs.2021.103729DOI Listing
October 2021

Pathogenesis, MicroRNA-122 Gene-Regulation, and Protective Immune Responses After Acute Equine Hepacivirus Infection.

Hepatology 2021 09 11;74(3):1148-1163. Epub 2021 Jun 11.

Copenhagen Hepatitis C Program (CO-HEP), Department of Infectious Diseases, Hvidovre Hospital and Department of Immunology and Microbiology, University of Copenhagen, Copenhagen, Denmark.

Background And Aims: Equine hepacivirus (EqHV) is phylogenetically the closest relative of HCV and shares genome organization, hepatotropism, transient or persistent infection outcome, and the ability to cause hepatitis. Thus, EqHV studies are important to understand equine liver disease and further as an outbred surrogate animal model for HCV pathogenesis and protective immune responses. Here, we aimed to characterize the course of EqHV infection and associated protective immune responses.

Approach And Results: Seven horses were experimentally inoculated with EqHV, monitored for 6 months, and rechallenged with the same and, subsequently, a heterologous EqHV. Clearance was the primary outcome (6 of 7) and was associated with subclinical hepatitis characterized by lymphocytic infiltrate and individual hepatocyte necrosis. Seroconversion was delayed and antibody titers waned slowly. Clearance of primary infection conferred nonsterilizing immunity, resulting in shortened duration of viremia after rechallenge. Peripheral blood mononuclear cell responses in horses were minimal, although EqHV-specific T cells were identified. Additionally, an interferon-stimulated gene signature was detected in the liver during EqHV infection, similar to acute HCV in humans. EqHV, as HCV, is stimulated by direct binding of the liver-specific microRNA (miR), miR-122. Interestingly, we found that EqHV infection sequesters enough miR-122 to functionally affect gene regulation in the liver. This RNA-based mechanism thus could have consequences for pathology.

Conclusions: EqHV infection in horses typically has an acute resolving course, and the protective immune response lasts for at least a year and broadly attenuates subsequent infections. This could have important implications to achieve the primary goal of an HCV vaccine; to prevent chronicity while accepting acute resolving infection after virus exposure.
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http://dx.doi.org/10.1002/hep.31802DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8435542PMC
September 2021

Equine leptospirosis: Experimental challenge of Leptospira interrogans serovar Bratislava fails to establish infection in naïve horses.

Equine Vet J 2021 Jul 25;53(4):845-854. Epub 2021 Mar 25.

Department of Population Medicine and Diagnostic Sciences, College of Veterinary Medicine, Cornell University, Ithaca, NY, USA.

Background: Little information is available about experimental inoculation of leptospirosis in horses and the pathogenicity of Leptospira interrogans serovar Bratislava in this host.

Objectives: To determine the serological, clinical, pathological and haematological responses of horses to L. interrogans serovar Bratislava strain PigK151.

Study Design: Randomised controlled in vivo experiment.

Methods: Ten seronegative female foals were divided into 2 groups, control (n = 4) and challenged (n = 6). The challenged group received 1 × 10 leptospires divided equally between topical ocular and intraperitoneal injections. Blood and urine samples were analysed. The temperature was recorded daily for the first 9 days, then weekly. Sera were tested by microscopic agglutination test (MAT). Automated complete blood count, differential and chemistry panel were performed. Histopathological analysis was performed on sections of liver, kidney, urinary bladder, uterine body and pineal gland. Sample culturing was performed from blood, urine, liver, kidney, reproductive tract and vitreous humour.

Results: No pyrexia was noted. PCR and culture were negative from all samples. Differences between groups were found in CBC, differential counts and serum biochemistry panel (or profile), suggesting that leptospiral challenge triggered an inflammatory response. No evidence of leptospirosis was found from histopathological analysis. All challenged foals developed a humoral response. The MAT allowed the confirmation of the infecting serovar at a later stage, but it also revealed cross-reactive results that were further explained by genomic analysis.

Main Limitations: This experimental challenge had two main limitations: (a) the results might have varied if another strain from the same serovar had been used and (b) the use of another route of infection and a higher bacterial dose might have achieved colonisation.

Conclusions: Based on these findings, it may suggest that L. interrogans serovar Bratislava is neither pathogenic nor host-adapted serovar for horses, although these results might have varied if another strain from the same serovar had been used instead.
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http://dx.doi.org/10.1111/evj.13442DOI Listing
July 2021

Investigating the pathogenesis of high-serum gamma-glutamyl transferase activity in Thoroughbred racehorses: A series of case-control studies.

Equine Vet J 2022 Jan 8;54(1):39-51. Epub 2021 Mar 8.

Department of Clinical Sciences, Cornell College of Veterinary Medicine, Cornell University, Ithaca, NY, USA.

Background: High-serum γ-Glutamyl Transferase (GGT) activity has been associated with and thought to be a marker of maladaptation to training and possibly poor performance in racehorses, but the cause is unknown.

Objectives: To investigate possible metabolic and infectious causes for the high GGT syndrome.

Study Design: Pilot case-control study and nested case-control study.

Methods: The case-control study in 2017 included 16 horses (8 cases and 8 controls with median [range] serum GGT 82 [74-148] and 22 [19-28] IU/L, respectively) from the same stable. In 2018, similar testing was performed in a nested case-control study that identified 27 case (serum GGT 50 ≥ IU/L)-control pairs from three stables for further testing. Serum liver chemistries, selenium measurements, viral PCR and metabolomics were performed.

Results: No differences were found in frequency of detection of viral RNA/DNA or copy numbers for equine hepacivirus (EqHV) and parvovirus-hepatitis (EqPV-H) between cases and controls. Mild increases in hepatocellular injury and cholestatic markers in case vs control horses suggested a degree of liver disease in a subset of cases. Metabolomic and individual bile acid testing showed differences in cases compared with controls, including increased abundance of pyroglutamic acid and taurine-conjugated bile acids, and reduced abundance of Vitamin B6. Selenium concentrations, although within or above the reference intervals, were also lower in case horses in both studies.

Main Limitations: Observational study design did not allow us to make causal inferences.

Conclusions: We conclude that high GGT syndrome is likely a complex metabolic disorder and that viral hepatitis was not identified as a cause for this syndrome in this cohort of racehorses. Our results support a contribution of oxidative stress and cholestasis in its pathophysiology.
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http://dx.doi.org/10.1111/evj.13435DOI Listing
January 2022

Single-cell resolution landscape of equine peripheral blood mononuclear cells reveals diverse cell types including T-bet B cells.

BMC Biol 2021 01 22;19(1):13. Epub 2021 Jan 22.

Department of Microbiology, Icahn School of Medicine at Mount Sinai, 1 Gustave L. Levy Place, New York, NY, 10029, USA.

Background: Traditional laboratory model organisms represent a small fraction of the diversity of multicellular life, and findings in any given experimental model often do not translate to other species. Immunology research in non-traditional model organisms can be advantageous or even necessary, such as when studying host-pathogen interactions. However, such research presents multiple challenges, many stemming from an incomplete understanding of potentially species-specific immune cell types, frequencies, and phenotypes. Identifying and characterizing immune cells in such organisms is frequently limited by the availability of species-reactive immunophenotyping reagents for flow cytometry, and insufficient prior knowledge of cell type-defining markers.

Results: Here, we demonstrate the utility of single-cell RNA sequencing (scRNA-Seq) to characterize immune cells for which traditional experimental tools are limited. Specifically, we used scRNA-Seq to comprehensively define the cellular diversity of equine peripheral blood mononuclear cells (PBMC) from healthy horses across different breeds, ages, and sexes. We identified 30 cell type clusters partitioned into five major populations: monocytes/dendritic cells, B cells, CD3PRF1 lymphocytes, CD3PRF1 lymphocytes, and basophils. Comparative analyses revealed many cell populations analogous to human PBMC, including transcriptionally heterogeneous monocytes and distinct dendritic cell subsets (cDC1, cDC2, plasmacytoid DC). Remarkably, we found that a majority of the equine peripheral B cell compartment is comprised of T-bet B cells, an immune cell subpopulation typically associated with chronic infection and inflammation in human and mouse.

Conclusions: Taken together, our results demonstrate the potential of scRNA-Seq for cellular analyses in non-traditional model organisms and form the basis for an immune cell atlas of horse peripheral blood.
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http://dx.doi.org/10.1186/s12915-020-00947-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7820527PMC
January 2021

Evaluation of new leptospiral antigens for the diagnosis of equine leptospirosis: An approach using pan-genomic analysis, reverse vaccinology and antigenic selection.

Equine Vet J 2021 Sep 3;53(5):1025-1035. Epub 2020 Dec 3.

Department of Population Medicine and Diagnostic Sciences, College of Veterinary Medicine, Cornell University, Ithaca, New York, USA.

Background: The current gold standard diagnostic test for leptospirosis is the microscopic agglutination test (MAT), which has many drawbacks; therefore, the development of a better and easier serological test for leptospirosis is needed.

Objectives: To apply reverse vaccinology (RV) and antigenic selection on the assortment of leptospiral targets and evaluate their potential for use as reagents for the diagnosis of equine leptospirosis.

Study Design: Cross-sectional study.

Methods: The antigenic selection parameters were: proteins with antigenicity score ≥0.5 (VaxiJen), at least one B cell epitope and size between 10 and 275 KDa. New leptospiral proteins were cloned, expressed and serologically screened against equine sera (n = 128) on a single analysis and comparative combinations. Sensitivity (Se) and specificity (Sp), accuracy, positive predictive value (PPV) and negative predictive value (NPV) were calculated. A BLAST with nucleotide and protein sequences was used to identify the serovar or species specificity.

Main Limitations: This cross-sectional analysis had three main limitations: (a) The equine sera used in these tests were limited to sera submitted to the Animal Health Diagnosis Center and were only tested against seven serovars; (b) MAT results were considered being 'perfect', and the highest titre presented was considered being the infecting serovar, which may not hold true; (c) The strains used to represent the serovars and the limited number of different serovars and species included in the genetic analysis, which leads to the possibility that these proteins might be present in different species or serovars that perhaps would be seroprevalent in another geographic region.

Conclusions: The new leptospiral antigens described in this research could increase the sensitivity and specificity of ELISA for detection of Leptospira exposure and the detection of leptospirosis in horses along with support from other clinical signs. Some of these new antigens might be used to improve the detection of infecting serovar.
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http://dx.doi.org/10.1111/evj.13380DOI Listing
September 2021

Equine pegiviruses cause persistent infection of bone marrow and are not associated with hepatitis.

PLoS Pathog 2020 07 10;16(7):e1008677. Epub 2020 Jul 10.

Copenhagen Hepatitis C Program (CO-HEP), Department of Infectious Diseases, Hvidovre Hospital and Department of Immunology and Microbiology, University of Copenhagen, Copenhagen, Denmark.

Pegiviruses frequently cause persistent infection (as defined by >6 months), but unlike most other Flaviviridae members, no apparent clinical disease. Human pegivirus (HPgV, previously GBV-C) is detectable in 1-4% of healthy individuals and another 5-13% are seropositive. Some evidence for infection of bone marrow and spleen exists. Equine pegivirus 1 (EPgV-1) is not linked to disease, whereas another pegivirus, Theiler's disease-associated virus (TDAV), was identified in an outbreak of acute serum hepatitis (Theiler's disease) in horses. Although no subsequent reports link TDAV to disease, any association with hepatitis has not been formally examined. Here, we characterized EPgV-1 and TDAV tropism, sequence diversity, persistence and association with liver disease in horses. Among more than 20 tissue types, we consistently detected high viral loads only in serum, bone marrow and spleen, and viral RNA replication was consistently identified in bone marrow. PBMCs and lymph nodes, but not liver, were sporadically positive. To exclude potential effects of co-infecting agents in experimental infections, we constructed full-length consensus cDNA clones; this was enabled by determination of the complete viral genomes, including a novel TDAV 3' terminus. Clone derived RNA transcripts were used for direct intrasplenic inoculation of healthy horses. This led to productive infection detectable from week 2-3 and persisting beyond the 28 weeks of study. We did not observe any clinical signs of illness or elevation of circulating liver enzymes. The polyprotein consensus sequences did not change, suggesting that both clones were fully functional. To our knowledge, this is the first successful extrahepatic viral RNA launch and the first robust reverse genetics system for a pegivirus. In conclusion, equine pegiviruses are bone marrow tropic, cause persistent infection in horses, and are not associated with hepatitis. Based on these findings, it may be appropriate to rename the group of TDAV and related viruses as EPgV-2.
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http://dx.doi.org/10.1371/journal.ppat.1008677DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7375656PMC
July 2020

Tropism, pathology, and transmission of equine parvovirus-hepatitis.

Emerg Microbes Infect 2020 20;9(1):651-663. Epub 2020 Mar 20.

Baker Institute for Animal Health, Cornell University College of Veterinary Medicine, Ithaca, NY, USA.

Equine parvovirus-hepatitis (EqPV-H) has recently been associated with cases of Theiler's disease, a form of fulminant hepatic necrosis in horses. To assess whether EqPV-H is the cause of Theiler's disease, we first demonstrated hepatotropism by PCR on tissues from acutely infected horses. We then experimentally inoculated horses with EqPV-H and 8 of 10 horses developed hepatitis. One horse showed clinical signs of liver failure. The onset of hepatitis was temporally associated with seroconversion and a decline in viremia. Liver histology and hybridization showed lymphocytic infiltrates and necrotic EqPV-H-infected hepatocytes. We next investigated potential modes of transmission. Iatrogenic transmission via allogeneic stem cell therapy for orthopedic injuries was previously suggested in a case series of Theiler's disease, and was demonstrated here for the first time. Vertical transmission and mechanical vectoring by horse fly bites could not be demonstrated in this study, potentially due to limited sample size. We found EqPV-H shedding in oral and nasal secretions, and in feces. Importantly, we could demonstrate EqPV-H transmission via oral inoculation with viremic serum. Together, our findings provide additional information that EqPV-H is the likely cause of Theiler's disease and that transmission of EqPV-H occurs via both iatrogenic and natural routes.
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http://dx.doi.org/10.1080/22221751.2020.1741326DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7144241PMC
March 2020

First report of equine parvovirus-hepatitis-associated Theiler's disease in Europe.

Equine Vet J 2020 Nov 25;52(6):841-847. Epub 2020 Mar 25.

Department of Clinical Sciences, College of Veterinary Medicine, Cornell University, Ithaca, NY, USA.

Background: Equine parvovirus-hepatitis (EqPV-H) has been proposed as the aetiological cause of Theiler's disease, also known as serum hepatitis. EqPV-H-associated Theiler's disease has not been previously reported in Europe.

Objectives: To determine whether EqPV-H infection was associated with a 2018-2019 outbreak of Theiler's disease in four horses on a studfarm.

Study Design: Descriptive case series.

Methods: The medical records of four horses from the same farm diagnosed with fatal Theiler's disease were examined retrospectively. Information collected included a clinical history, physical examination findings, tetanus antitoxin exposure, serum biochemistry and necropsy reports. Liver tissue from all four horses was tested for EqPV-H using PCR and in situ hybridisation (ISH) assays.

Results: Three of the horses had a history of recent (7-11 weeks) tetanus antitoxin administration. Liver tissue from all four horses tested positive for EqPV-H with PCR. In situ hybridisation revealed a widespread distribution of viral nucleic acid in hepatocytes in one case, and a more sporadic distribution in the remaining three cases.

Main Limitations: Case controls were not available from the farm in question given the retrospective nature of analysis.

Conclusions: This case series documents the first reported EqPV-H-associated Theiler's disease in Europe and the first use of ISH to visualise the viral nucleic acid in liver tissues of horses with Theiler's disease.
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http://dx.doi.org/10.1111/evj.13254DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7483838PMC
November 2020

Clinical Pathology in the Adult Sick Horse: The Gastrointestinal System and Liver.

Vet Clin North Am Equine Pract 2020 Apr 22;36(1):105-120. Epub 2020 Jan 22.

Department of Clinical Sciences, College of Veterinary Medicine, Cornell University, 144 East Avenue, Ithaca NY 14853, USA.

The gastrointestinal tract and liver comprise key components of the equine digestive system and together have important functions in metabolism, digestion, absorption, detoxification, and synthesis. Disorders of the gastrointestinal tract and liver are common in clinical practice and can cause a variety of clinical signs. Hematologic and biochemical analysis can be helpful for identifying organ dysfunction, narrowing down the differential diagnostic list, and monitoring progress and response to treatment. This article details hematologic and biochemical tests that are important in the evaluation of intestinal and hepatic diseases and reviews bloodwork trends frequently observed in adult horses affected by enteropathy or hepatopathy.
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http://dx.doi.org/10.1016/j.cveq.2019.11.004DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7127838PMC
April 2020

Utility and accuracy of a smartphone-based electrocardiogram device as compared to a standard base-apex electrocardiogram in the horse.

Res Vet Sci 2019 Aug 3;125:141-147. Epub 2019 Jun 3.

Department of Clinical Sciences and Advanced Medicine-Philadelphia, Matthew J. Ryan Veterinary Hospital, School of Veterinary Medicine, University of Pennsylvania, Philadelphia, PA 19104, United States of America. Electronic address:

Objective: Evaluate accuracy and utility of a smartphone-based ECG device compared to a standard base-apex lead ECG in horses.

Methods: ECGs were acquired prospectively from 28 client-owned horses at 2 equine referral hospitals. Twenty-five pairs of 30-s ECG recordings were acquired simultaneously from 23 horses with a smartphone ECG device (a bi-polar single lead recorder coupled to a smartphone with an ECG application) and with a standard base-apex lead ECG; 2 horses provided two pairs of simultaneously acquired ECGs. In one horse, the ECGs pairs were recorded immediately sequentially. An additional 7 smartphone ECGs were recorded from 5 horses without contemporaneous reference ECGs. Three observers independently evaluated all ECGs without knowledge of ECG pairing. Inter- and intra-observer agreement between the 2 ECG modalities was evaluated for rhythm diagnosis and QRS polarity. Heart rate agreement was also evaluated.

Results: Intra-observer agreement for rhythm assessment was very high; one observer diagnosed the same cardiac rhythm on both recordings in 24/26 instances and two observers agreed in 25/26 instances. The polarity of the QRS complex was similar on ECGs acquired simultaneously by both systems. Heart rates calculated from ECG pairs were within 1 beat of each other.

Conclusions: The smartphone-acquired ECG accurately identified cardiac rhythm and heart rate in most horses. In one case, small size of the complexes precluded identification of P waves on smartphone-acquired ECGs, resulting in a misdiagnosis. The smartphone-acquired ECG device might allow veterinarians to evaluate and monitor cardiac arrhythmias relatively inexpensively in field or hospital settings.
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http://dx.doi.org/10.1016/j.rvsc.2019.05.018DOI Listing
August 2019

Investigating the Risk of Equine Motor Neuron Disease in a Brazilian Stable and Successful Intervention.

J Equine Vet Sci 2019 06 27;77:132-138. Epub 2019 Mar 27.

Department of Population Medicine and Diagnostic Sciences, College of Veterinary Medicine, Cornell University, Ithaca, NY. Electronic address:

We carried out an investigation to identify the factors that predispose to the risk of equine motor neuron disease (EMND) and evaluated the long-term impact of an intervention. Data on several biomarkers, including antioxidants (α-tocopherols, β-carotenes, glutathione peroxidase (GSHPx)), and superoxide dismutase (SOD1), neurofilaments, and other putative risk factors hypothesized to associate with the likelihood of EMND were collected. The data were analyzed for their significance of association with the condition. The EMND outbreak started in 1991 and continued until 1998. A total of 69 EMND cases and 64 control horses met the inclusion criteria and were enrolled in the study. Most cases (74%) occurred in 1996 and 1997. Horses afflicted with EMND had significantly lower plasma levels of vitamin E than control horses (0.381 vs. 1.148 μg/mL). There were no significant differences in the levels of vitamin A, β-carotenes, GSHPx, or the activities of SOD1 between EMND cases and control horses. Horses afflicted with EMND had significantly higher serum levels of phosphorylated neurofilament heavy than controls (2.85 vs. 0.27 ng/mL). The probability of EMND diagnosis increased above 50% when the serum levels of phosphorylated neurofilament heavy increased beyond 2.54 ng/mL. Mixed and Brazilian breeds had a significantly higher risk of EMND in comparison to Standardbred horse among the study population. In 1997, there was a change in the diet where better quality green hay was used. The incidence of EMND dropped to 0 in 1 year after intervention and remained at that level for the past 20 years.
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http://dx.doi.org/10.1016/j.jevs.2019.02.024DOI Listing
June 2019

What Do We Know About Hepatitis Viruses in Horses?

Vet Clin North Am Equine Pract 2019 Aug 10;35(2):351-362. Epub 2019 May 10.

Department of Clinical Sciences, Cornell University College of Veterinary Medicine, 930 Campus Road, Box25, Ithaca, NY 14853, USA.

Theiler disease (serum hepatitis or idiopathic acute hepatic necrosis) has long been suspected to have a viral etiology. Four viruses have been described in association with hepatitis in horses. Further investigation suggests equine pegivirus and Theiler disease-associated virus (a second pegivirus) are neither hepatotropic nor pathogenic. Nonprimate hepacivirus (NPHV) causes subclinical disease in experimental models and has been associated with hepatitis in some clinical cases. Equine parvovirus-hepatitis (EqPV-H) experimentally causes subclinical-to-clinical liver disease and is found in the vast majority of Theiler disease cases. EqPV-H is likely of clinical significance, whereas the significance of NPHV is unknown.
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http://dx.doi.org/10.1016/j.cveq.2019.03.001DOI Listing
August 2019

Response to: "Concern Regarding the Publication by Posbergh et al".

J Equine Vet Sci 2019 01 30;72:124-125. Epub 2018 Oct 30.

Department of Animal Science, College of Agriculture & Life Sciences, Cornell University, Ithaca, NY. Electronic address:

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http://dx.doi.org/10.1016/j.jevs.2018.10.022DOI Listing
January 2019

Neuroborreliosis in a horse with common variable immunodeficiency.

J Vet Diagn Invest 2019 Mar 19;31(2):241-245. Epub 2019 Jan 19.

Departments of Biomedical Sciences, Section of Anatomic Pathology (Pecoraro, Miller, Duhamel), College of Veterinary Medicine, Cornell University, Ithaca, NY.

Common variable immunodeficiency (CVID) is a rare condition in adult horses characterized by hypogammaglobulinemia and increased susceptibility to parasitic and bacterial infections, including recurrent respiratory diseases, septicemia, and meningitis. Lyme disease is often included as a differential diagnosis in CVID horses with signs of meningitis; however, the Borrelia burgdorferi organism has not been demonstrated previously within central nervous system tissues of CVID horses with neurologic disease, to our knowledge. We report herein a case of neuroborreliosis in a CVID horse, confirmed by combined immunologic testing, histopathology, real-time PCR assay, fluorescent in situ hybridization, and immunohistochemical staining. Implications of these findings include heightened monitoring of CVID horses for Lyme disease in endemic areas and appropriate therapy in the case of neurologic disease.
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http://dx.doi.org/10.1177/1040638718824146DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6838834PMC
March 2019

Viral testing of 18 consecutive cases of equine serum hepatitis: A prospective study (2014-2018).

J Vet Intern Med 2019 Jan 5;33(1):251-257. Epub 2018 Dec 5.

Department of Clinical Sciences, College of Veterinary Medicine, Cornell University, Ithaca, New York.

Background: Three flaviviruses (equine pegivirus [EPgV]; Theiler's disease-associated virus [TDAV]; non-primate hepacivirus [NPHV]) and equine parvovirus (EqPV-H) are present in equine blood products; the TDAV, NPHV, and EqPV-H have been suggested as potential causes of serum hepatitis.

Objective: To determine the prevalence of these viruses in horses with equine serum hepatitis.

Animals: Eighteen horses diagnosed with serum hepatitis, enrolled from US referral hospitals.

Methods: In the prospective case study, liver, serum, or both samples were tested for EPgV, TDAV, NPHV, and EqPV-H by PCR.

Results: Both liver tissue and serum were tested for 6 cases, serum only for 8 cases, and liver only for 4 cases. Twelve horses received tetanus antitoxin (TAT) 4-12.7 weeks (median = 8 weeks), 3 horses received commercial equine plasma 6-8.6 weeks, and 3 horses received allogenic stem cells 6.4-7.6 weeks before the onset of hepatic failure. All samples were TDAV negative. Two of 14 serum samples were NPHV-positive. Six of 14 serum samples were EPgV-positive. All liver samples were NPHV-negative and EPgV-negative. EqPV-H was detected in the serum (N = 8), liver (N = 4), or both samples (N = 6) of all 18 cases. The TAT of the same lot number was available for virologic testing in 10 of 12 TAT-associated cases, and all 10 samples were EqPV-H positive.

Conclusions And Clinical Importance: We demonstrated EqPV-H in 18 consecutive cases of serum hepatitis. EPgV, TDAV, and NPHV were not consistently present. This information should encourage blood product manufacturers to test for EqPV-H and eliminate EqPV-H-infected horses from their donor herds.
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http://dx.doi.org/10.1111/jvim.15368DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6335536PMC
January 2019

Viral testing of 10 cases of Theiler's disease and 37 in-contact horses in the absence of equine biologic product administration: A prospective study (2014-2018).

J Vet Intern Med 2019 Jan 6;33(1):258-265. Epub 2018 Dec 6.

Department of Clinical Sciences, College of Veterinary Medicine, Cornell University, Ithaca, New York.

Background: A novel equine parvovirus (EqPV-H) was recently discovered in the equine liver with Theiler's disease.

Objectives: To determine the prevalence of EqPV-H infection in naturally occurring Theiler's disease cases and in-contact horses in the absence of historical equine biologic product administration.

Animals: Ten cases of Theiler's disease from 6 separate properties were included in the study, based on the criteria of acute onset of clinical signs of liver failure with laboratory or histopathologic findings characteristic of Theiler's disease and no history of receiving an equine biologic product within the preceding 4 months. In addition, 37 in-contact horses from 4 of the 6 properties were screened for EqPV-H infection and hepatitis.

Methods: In prospective case series, cases were diagnosed with Theiler's disease by the attending veterinarian and were tested for EqPV-H by PCR of liver or serum. In-contact horses were assessed via serum chemistry and PCR at the attending veterinarian's discretion. Hepatitis was defined as serum gamma-glutamyltransferase activity above reference interval. The association of EqPV-H with hepatitis was determined by Fisher's exact test.

Results: Nine of 10 (90%) Theiler's disease cases and 54% of tested in-contact horses were EqPV-H positive. Hepatitis was significantly associated with EqPV-H infection (P = .036).

Conclusions And Clinical Importance: Although further study is required to identify EqPV-H as the causative agent of Theiler's disease, EqPV-H appears strongly associated with cases of fatal Theiler's disease and subclinical hepatitis in horses in contact with those cases. The prevalence of EqPV-H infection on affected properties can be high.
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http://dx.doi.org/10.1111/jvim.15362DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6335540PMC
January 2019

Persistent hypoglycemia associated with lipid storage myopathy in a paint foal.

J Vet Intern Med 2018 Jul 29;32(4):1442-1446. Epub 2018 Jun 29.

Department of Large Animal Clinical Sciences, Michigan State University, East Lansing, Michigan.

A 12-hours-old Paint filly was examined because of weakness and dull mentation after birth. Despite IV administered dextrose, the foal remained persistently hypoglycemic with increase in serum activity of muscle and liver enzymes. A postmortem diagnosis of lipid myopathy most similar to multiple acyl-CoA dehydrogenase deficiency (MADD) was confirmed by findings of myofiber lipid accumulation, elevated urine organic acids, and serum free acylcarnitines with respect to control foals. This report details a case of equine neonatal lipid storage myopathy with many biochemical characteristics of MADD. Lipid storage myopathies should be included as a differential diagnosis in foals with persistent weakness and hypoglycemia.
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http://dx.doi.org/10.1111/jvim.15218DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6060329PMC
July 2018

New Parvovirus Associated with Serum Hepatitis in Horses after Inoculation of Common Biological Product.

Emerg Infect Dis 2018 02;24(2):303-310

Equine serum hepatitis (i.e., Theiler's disease) is a serious and often life-threatening disease of unknown etiology that affects horses. A horse in Nebraska, USA, with serum hepatitis died 65 days after treatment with equine-origin tetanus antitoxin. We identified an unknown parvovirus in serum and liver of the dead horse and in the administered antitoxin. The equine parvovirus-hepatitis (EqPV-H) shares <50% protein identity with its phylogenetic relatives of the genus Copiparvovirus. Next, we experimentally infected 2 horses using a tetanus antitoxin contaminated with EqPV-H. Viremia developed, the horses seroconverted, and acute hepatitis developed that was confirmed by clinical, biochemical, and histopathologic testing. We also determined that EqPV-H is an endemic infection because, in a cohort of 100 clinically normal adult horses, 13 were viremic and 15 were seropositive. We identified a new virus associated with equine serum hepatitis and confirmed its pathogenicity and transmissibility through contaminated biological products.
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http://dx.doi.org/10.3201/eid2402.171031DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5782890PMC
February 2018

miRNA independent hepacivirus variants suggest a strong evolutionary pressure to maintain miR-122 dependence.

PLoS Pathog 2017 10 30;13(10):e1006694. Epub 2017 Oct 30.

Laboratory of Virology and Infectious Disease, Center for the Study of Hepatitis C, The Rockefeller University, New York, NY, United States of America.

Hepatitis C virus (HCV) requires the liver specific micro-RNA (miRNA), miR-122, to replicate. This was considered unique among RNA viruses until recent discoveries of HCV-related hepaciviruses prompting the question of a more general miR-122 dependence. Among hepaciviruses, the closest known HCV relative is the equine non-primate hepacivirus (NPHV). Here, we used Argonaute cross-linking immunoprecipitation (AGO-CLIP) to confirm AGO binding to the single predicted miR-122 site in the NPHV 5'UTR in vivo. To study miR-122 requirements in the absence of NPHV-permissive cell culture systems, we generated infectious NPHV/HCV chimeric viruses with the 5' end of NPHV replacing orthologous HCV sequences. These chimeras were viable even in cells lacking miR-122, although miR-122 presence enhanced virus production. No other miRNAs bound this region. By random mutagenesis, we isolated HCV variants partially dependent on miR-122 as well as robustly replicating NPHV/HCV variants completely independent of any miRNAs. These miRNA independent variants even replicate and produce infectious particles in non-hepatic cells after exogenous delivery of apolipoprotein E (ApoE). Our findings suggest that miR-122 independent HCV and NPHV variants have arisen and been sampled during evolution, yet miR-122 dependence has prevailed. We propose that hepaciviruses may use this mechanism to guarantee liver tropism and exploit the tolerogenic liver environment to avoid clearance and promote chronicity.
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http://dx.doi.org/10.1371/journal.ppat.1006694DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5679655PMC
October 2017

Phosphorylated neurofilament H (pNF-H) as a potential diagnostic marker for neurological disorders in horses.

Res Vet Sci 2017 Oct 18;114:401-405. Epub 2017 Jul 18.

College of Veterinary Medicine, Cornell University, Ithaca, 14853, NY, USA. Electronic address:

The current study aimed at the investigating the potential use of phosphorylated neurofilament H (pNF-H) as a diagnostic biomarker for neurologic disorders in the horse. Paired serum and cerebrospinal fluid (CSF) samples (n=88) and serum only (n=30) were obtained from horses diagnosed with neurologic disorders and clinically healthy horses as control. The neurologic horses consisted of equine protozoal myeloencephalitis (EPM) (38 cases) and cervical vertebral malformation (CVM) (23 cases). Levels of pNF-H were determined using an ELISA. The correlation between CSF and serum concentrations of pNF-H was evaluated using Spearman's Rank test and the significance of the difference among the groups was assessed using a nonparametric test. Horses had higher pNF-H levels in the CSF than serum. Horses afflicted with EPM had significantly higher serum pNF-H levels in comparison to controls or CVM cases. The correlation between CSF and serum pNF-H levels was poor in both the whole study population and among subgroups of horses included in the study. There was significant association between the likelihood of EPM and the concentrations of pNF-H in either the serum or CSF. These data suggest that pNF-H could be detected in serum and CSF samples from neurologic and control horses. This study demonstrated that pNF-H levels in serum and CSF have the potential to provide objective information to help in the early diagnosis of horses afflicted with neurologic disorders.
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http://dx.doi.org/10.1016/j.rvsc.2017.07.020DOI Listing
October 2017

Randomized placebo-controlled study of the effects of Yunnan Baiyao on hemostasis in horses.

Am J Vet Res 2017 Aug;78(8):969-976

OBJECTIVE To determine effects of oral administration of Yunnan Baiyao on platelet activation, coagulation, and fibrinolysis in healthy horses. ANIMALS 12 healthy adult horses. PROCEDURES In a randomized blinded crossover study that included a 4-week washout period between treatments, horses were orally administered a paste containing Yunnan Baiyao (15 mg/kg) or placebo at 12-hour intervals for 3 days. Blood samples were collected before start of treatment (time 0) and at 24 and 72 hours for a CBC, measurement of fibrinogen concentration, coagulation screening tests, and a panel of assays to assess platelet activation (including ADP- and collagen-induced aggregation and closure times, flow-cytometric variables of platelet-leukocyte aggregates, platelet membrane P-selectin and phosphatidylserine expression, and microparticle release), von Willebrand factor (vWF) concentration, and cofactor activity. In addition, thrombelastography was used to evaluate fibrin formation in tissue factor-activated whole blood and plasma and to assess tissue plasminogen activator-induced plasma fibrinolysis. For each treatment, values obtained before and 72 hours after start of administration were compared by use of Wilcoxon signed rank tests. RESULTS Yunnan Baiyao treatment had no significant effect on any hemostatic variable, compared with results for the placebo treatment. CONCLUSIONS AND CLINICAL RELEVANCE Administration of Yunnan Baiyao at a dosage typically used in clinical practice had no effect on in vitro measures of platelet or vWF function and no enhancement of fibrin-clot formation or stability. Any hemostatic actions of Yunnan Baiyao may require higher dosages or result from cell-surface interactions at sites of vascular and tissue injury not examined in this study.
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http://dx.doi.org/10.2460/ajvr.78.8.969DOI Listing
August 2017

Acute leukemia in six horses (1990-2012).

J Vet Diagn Invest 2017 Jul 3;29(4):529-535. Epub 2017 May 3.

Departments of Clinical Sciences, Cornell University, Ithaca, NY (Barrell, Felippe, Divers), College of Veterinary Medicine, Cornell University, Ithaca, NY.

Acute leukemia is rare in horses. Herein we describe historical, clinicopathologic, and postmortem findings in 6 horses with acute leukemia. Medical records of horses with >20% bone marrow blasts and cytochemical or immunophenotyping results were reviewed. Affected horses were 2-8 y of age and of different breeds and sex. Horses were presented acutely with nonspecific signs (e.g., fever, lethargy). Characteristic hemogram findings were bi- or pancytopenia with low blast numbers. Histologic examination revealed extramedullary infiltrates, especially in lymph nodes, spleen, kidney, liver, and lungs. Leukemias were classified as B-cell ( n = 3) and acute myeloid leukemia (AML) ( n = 3). Tumors in 4 cases expressed multiple lineage markers, which complicated classification. Acute leukemia should be suspected in horses with moderate-to-severe bi- or pancytopenia. Blood smears should be reviewed for neoplastic cells, and bone marrow examination is required for diagnosis. Leukemia classification is best achieved using combined morphologic, cytochemical, and immunophenotyping results.
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http://dx.doi.org/10.1177/1040638717707724DOI Listing
July 2017
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