Data standardization implementation and applications within and among diagnostic laboratories: integrating and monitoring enteric coronaviruses

Every day, thousands of samples from diverse populations of animals are submitted to veterinary diagnostic laboratories (VDLs) for testing. Each VDL has its own laboratory information management system (LIMS), with processes and procedures to capture submission information, perform laboratory tests, define the boundaries of test results (i.e., positive or negative), and report results, in addition to internal business and accounting applications. Enormous quantities of data are accumulated and stored within VDL LIMSs. There is a need for platforms that allow VDLs to exchange and share portions of laboratory data using standardized, reliable, and sustainable information technology processes. Here we report concepts and applications for standardization and aggregation of data from swine submissions to multiple VDLs to detect and monitor porcine enteric coronaviruses by RT-PCR. Oral fluids, feces, and fecal swabs were the specimens submitted most frequently for enteric coronavirus testing. Statistical algorithms were used successfully to scan and monitor the overall and state-specific percentage of positive submissions. Major findings revealed a consistently recurrent seasonal pattern, with the highest percentage of positive submissions detected during December–February for porcine epidemic diarrhea virus, porcine deltacoronavirus, and transmissible gastroenteritis virus (TGEV). After 2014, very few submissions tested positive for TGEV. Monitoring VDL data proactively has the potential to signal and alert stakeholders early of significant changes from expected detection. We demonstrate the importance of, and applications for, data organized and aggregated by using LOINC and SNOMED CTs, as well as the use of customized messaging to allow inter-VDL exchange of information.     

Recombinant human thyrotropin in veterinary medicine: current use and future perspectives

Recombinant human thyrotropin (rhTSH) was developed after bovine thyrotropin (bTSH) was no longer commercially available. It was approved by the Food and Drug Administration (FDA) and the European Medicines Agency (EMEA) as an aid to diagnostic follow-up of differentiated thyroid carcinoma in humans and for thyroid remnant ablation with radioiodine. In addition, rhTSH is used in human medicine to evaluate thyroid reserve capacity and to enhance radioiodine uptake in patients with metastatic thyroid cancer and multinodular goiter. Likewise, rhTSH has been used in veterinary medicine over the last decade. The most important veterinary use of rhTSH is thyroidal functional reserve testing for the diagnosis of canine hypothyroidism. Recent pilot studies performed at Ghent University in Belgium have investigated the use of rhTSH to optimize radioiodine treatment of canine thyroid carcinoma and feline hyperthyroidism. Radioiodine treatment optimization may allow a decreased therapeutic dosage of radioiodine and thus may improve radioprotection. This review outlines the current uses of rhTSH in human and veterinary medicine, emphasizing research performed in dogs and cats, as well as potential future applications.     

Fetal well-being assessment in bovine near-term gestations: current knowledge and future perspectives arising from comparative medicine

Cloning technology is associated with multiple losses throughout pregnancy and in the neonatal period. Any maternal or fetal disease can compromise pregnancy. A paucity of data are available on bovine fetal well-being in late pregnancy; development of well-being assessment methods might augment early diagnosis of abnormal pregnancy or fetal distress, allowing early intervention. This review presents the current knowledge on fetal well-being based on bovine, ovine, equine, and human studies, as well as interesting research parameters that have been studied in other species and not yet investigated in cattle. Transabdominal ultrasonography allows for diagnosis of large placentomes and hydrallantois that frequently accompany clone pregnancies. Fetal inactivity or large hyperechoic particles imaged within the fetal annexes are associated with fetal distress or death, and should be reassessed to confirm compromised pregnancy. Measurements of different fetal parameters (thoracic aorta, metacarpal or metatarsal thickness) could be reliable tools for early detection of the large offspring syndrome commonly found in cloned calves.     

A proposal to leverage high-quality veterinary diagnostic laboratory large data streams for animal health,public health,and One Health

Test data generated by ~60 accredited member laboratories of the American Association of Veterinary Laboratory Diagnosticians (AAVLD) is of exceptional quality. These data are captured by 1 of 13 laboratory information management systems (LIMSs) developed specifically for veterinary diagnostic laboratories (VDLs). Beginning ~2000, the National Animal Health Laboratory Network (NAHLN) developed an electronic messaging system for LIMS to automatically send standardized data streams for 14 select agents to a national repository. This messaging enables the U.S. Department of Agriculture to track and respond to high-consequence animal disease outbreaks such as highly pathogenic avian influenza. Because of the lack of standardized data collection in the LIMSs used at VDLs, there is, to date, no means of summarizing VDL large data streams for multi-state and national animal health studies or for providing near-real-time tracking for hundreds of other important animal diseases in the United States that are detected routinely by VDLs. Further, VDLs are the only state and federal resources that can provide early detection and identification of endemic and emerging zoonotic diseases. Zoonotic diseases are estimated to be responsible for 2.5 billion cases of human illness and 2.7 million deaths worldwide every year. The economic and health impact of the SARS-CoV-2 pandemic is self-evident. We review here the history and progress of data management in VDLs and discuss ways of seizing unexplored opportunities to advance data leveraging to better serve animal health, public health, and One Health.     

Acute phase proteins in dogs and cats: current knowledge and future perspectives

The acute phase response is a nonspecific inflammatory reaction of the host that occurs shortly after any tissue injury. The response includes changes in the concentration of plasma proteins called acute phase proteins (APPs), some of which decrease in concentration (negative APPs), such as albumin or transferrin, and others of which increase in concentration (positive APPs), such as C-reactive protein, serum amyloid A, haptoglobin, alpha-1-acid glycoprotein, and ceruloplasmin. Most positive APPs are glycoproteins synthesized mainly by hepatocytes upon stimulation by proinflammatory cytokines and released into the bloodstream. The acute phase response and clinical application of monitoring APPs in dogs and cats are reviewed in this article, including biochemical characteristics, assays developed for each individual APP, and preanalytic and analytic factors influencing APP results that should be taken into account for proper and adequate clinical interpretation. In addition, the diagnostic use of APPs and their possible application in monitoring treatment, which can be considered one of the most interesting and promising practical applications of these proteins, will be discussed. Finally, challenges and future developments of APPs in dogs and cats will be considered, because it is expected that new and cheaper automated assays for determination of the main APPs in small animals will contribute to a wider use of these proteins as biomarkers of infection and inflammatory lesions.     

Business intelligence tools to optimize the appropriateness of the diagnostic process for clinical and epidemiologic purposes in a multicenter veterinary pathology service

Laboratory tests provide essential support to the veterinary practitioner, and their use has grown exponentially. This growth is the result of several factors, such as the eradication of historical diseases, the occurrence of multifactorial diseases, and the obligation to control endemic and epidemic diseases. However, the introduction of novel techniques is counterbalanced by economic constraints, and the establishment of evidence- and consensus-based guidelines is essential to support the pathologist. Therefore, we developed standardized protocols, categorized by species, type of production, age, and syndrome at the Istituto Zooprofilattico Sperimentale delle Venezie (IZSVe), a multicenter institution for animal health and food safety. We have 72 protocols in use for livestock, poultry, and pets, categorized as, for example, “bovine enteric calf”, “rabbit respiratory”, “broiler articular”. Each protocol consists of a panel of tests, divided into ‘mandatory’ and ‘ancillary’, to be selected by the pathologist in order to reach the final diagnosis. After autopsy, the case is categorized into a specific syndrome, subsequently referred to as a syndrome-specific panel of analyses. The activity of the laboratories is monitored through a web-based dynamic reporting system developed using a business intelligence product (QlikView) connected to the laboratory information management system (IZILAB). On a daily basis, reports become available at general, laboratory, and case levels, and are updated as needed. The reporting system highlights epidemiologic variations in the field and allows verification of compliance with the protocols within the organization. The diagnostic protocols are revised annually to increase system efficiency and to address stakeholder requests.     

Trypanosoma cruzi: adaptation to its vectors and its hosts

American trypanosomiasis is a parasitic zoonosis that occurs throughout Latin America. The etiological agent, Trypanosoma cruzi, is able to infect almost all tissues of its mammalian hosts and spreads in the environment in multifarious transmission cycles that may or not be connected. This biological plasticity, which is probably the result of the considerable heterogeneity of the taxon, exemplifies a successful adaptation of a parasite resulting in distinct outcomes of infection and a complex epidemiological pattern. In the 1990s, most endemic countries strengthened national control programs to interrupt the transmission of this parasite to humans. However, many obstacles remain to the effective control of the disease. Current knowledge of the different components involved in elaborate system that is American trypanosomiasis (the protozoan parasite T. cruzi, vectors Triatominae and the many reservoirs of infection), as well as the interactions existing within the system, is still incomplete. The Triatominae probably evolve from predatory reduvids in response to the availability of vertebrate food source. However, the basic mechanisms of adaptation of some of them to artificial ecotopes remain poorly understood. Nevertheless, these adaptations seem to be associated with a behavioral plasticity, a reduction in the genetic repertoire and increasing developmental instability.     

In vitro production of porcine embryos: current status,future perspectives and alternative applications

The pig is considered to be a suitable source of cells and organs for xenotransplants, as well as a transgenic animal to produce specific proteins, given the biological similarities it shares with human beings. However, the in vitro embryo production system in pigs is inefficient compared with those in other mammals, such as cattle or mice. Although numerous modifications have been applied to improve the efficiency of in vitro embryo production systems in pigs, not much progress has been made to overcome the problem of polyspermy, and low developmental ability due to insufficient cytoplasmic abilities of in vitro matured oocytes and improper culture conditions for the in vitro produced embryos. Recent achievements, such as the establishment of chemically defined medium and utilization of ‘zona hardening’ technique, have gained some success. However, further research for the reduction of polyspermy and detrimental effects of the culture systems in pigs is still needed.     

Performance and rideability issues in horses as a manifestation of pain: A review of differential diagnosis and diagnostic approach

Nonspecific performance and rideability issues are more likely a manifestation of pain in the ridden horse rather than a true behavioural problem. A systematic and thorough investigation focusing on the potential presence of pain-related conditions is thus crucial in horses with such complaints. It can, however, be challenging to determine whether the complaint is indeed related to pain, where the pain is located, and what the underlying cause is. This review describes the challenges of pain recognition in ridden horses and summarises the recently developed ridden horse ethograms that might enable pain to be assessed in an objective, valid and reliable way. Furthermore, the differential diagnosis and diagnostic approach to horses presenting potentially pain-related performance and rideability issues are discussed.     

The Ontario Animal Health Network: enhancing disease surveillance and information sharing through integrative data sharing and management

The Ontario Animal Health Network (OAHN) is an innovative disease surveillance program created to enhance preparedness, early detection, and response to animal disease in Ontario. Laboratory data and, where available, abattoir condemnation data and clinical observations submitted by practicing veterinarians form the core of regular discussions of the species-sector networks. Each network is comprised of government veterinarians or specialists, epidemiologists, pathologists, university species specialists, industry stakeholders, and practicing veterinarians, as appropriate. Laboratorians provide data for diseases of interest as determined by the individual network, and network members provide analysis and context for the large volume of information. Networks assess data for disease trends and the emergence of new clinical syndromes, as well as generate information on the health and disease status for each sector in the province. Members assess data validity and quality, which may be limited by multiple factors. Interpretation of laboratory tests and antimicrobial resistance trends without available clinical histories can be challenging. Extrapolation of disease incidence or risk from laboratory submissions to broader species populations must be done with caution. Disease information is communicated in a variety of media to inform veterinary and agricultural sectors of regional disease risks. Through network engagement, information gaps have been addressed, such as educational initiatives to improve sample submissions and enhance diagnostic outcomes, and the development of applied network-driven research. These diverse network initiatives, developed after careful assessment of laboratory and other data, demonstrate that novel approaches to analysis and interpretation can result in a variety of disease risk mitigation actions.     

Development of a Medium-term Animal Model Using gpt Delta Rats to Evaluate Chemical Carcinogenicity and Genotoxicity

In this study, the potential for development of an animal model (GPG46) capable of rapidly detecting chemical carcinogenicity and the underlying mechanisms of action were examined in gpt delta rats using a reporter gene assay to detect mutations and a medium-term rat liver bioassay to detect tumor promotion. The tentative protocol for the GPG46 model was developed based on the results of dose-response exposure to diethylnitrosamine (DEN) and treatment with phenobarbital over time following DEN administration. Briefly, gpt delta rats were exposed to various chemicals for 4 weeks, followed by a partial hepatectomy (PH) to collect samples for an in vivo mutation assay. The mutant frequencies (MFs) of the reporter genes were examined as an indication of tumor initiation. A single intraperitoneal (ip) injection of 10 mg/kg DEN was administered to rats 18 h after the PH to initiate hepatocytes. Tumor-promoting activity was evaluated based on the development of glutathione S-transferase placental form (GST-P)-positive foci at week 10. The genotoxic carcinogens 2-acetylaminofluorene (2-AAF), 2-amino-3-methylimidazo [4,5-f] quinolone (IQ) and safrole (SF), the non-genotoxic carcinogens piperonyl butoxide (PBO) and phenytoin (PHE), the non-carcinogen acetaminophen (APAP) and the genotoxic non-hepatocarcinogen aristolochic acid (AA) were tested to validate the GPG46 model. The validation results indicate that the GPG46 model could be a powerful tool in understanding chemical carcinogenesis and provide valuable information regarding human risk hazards.     

Visualization and application of disease diagnosis codes for population health management using porcine diseases as a model

Accurate and timely results of diagnostic investigations and laboratory testing guide clinical interventions for the continuous improvement of animal health and welfare. Infectious diseases can severely limit the health, welfare, and productivity of populations of animals. Livestock veterinarians submit thousands of samples daily to veterinary diagnostic laboratories (VDLs) for disease diagnosis, pathogen monitoring, and surveillance. Individual diagnostic laboratory reports are immediately useful; however, aggregated historical laboratory data are increasingly valued by clinicians and decision-makers to identify changes in the health status of various animal populations over time and geographical space. The value of this historical information is enhanced by visualization of trends of agent detection, disease diagnosis, or both, which helps focus time and resources on the most significant pathogens and fosters more effective communication between livestock producers, veterinarians, and VDL professionals. Advances in data visualization tools allow quick, efficient, and often real-time scanning and analysis of databases to inform, guide, and modify animal health intervention algorithms. Value is derived at the farm, production system, or regional level. Visualization tools allow client-specific analyses, benchmarking, formulation of research questions, and monitoring the effects of disease management and precision farming practices. We present here the approach taken to visualize trends of disease occurrence using porcine disease diagnostic code data for the period 2010 to 2019. Our semi-automatic standardized creation of a visualization platform allowed the transformation of diagnostic report data into aggregated information to visualize and monitor disease diagnosis.     

Platelet abnormalities and platelet-to-lymphocyte ratios in canine immunosuppressant-responsive and non-responsive enteropathy: A retrospective study in 41 dogs

Few studies have examined platelet alterations in dogs with chronic enteropathy. Our aim was to investigate platelet count (PLT), mean platelet volume (MPV), and platelet-to-lymphocyte ratio (PLR) in dogs diagnosed with immunosuppressant-responsive enteropathy (IRE). In this retrospective study of 41 dogs, data regarding signalment, canine chronic enteropathy clinical activity index (CCECAI), endoscopic and histopathological scores, PLT, MPV, PLR, total serum protein concentrations, albumin, and iron were collected. Clinical response and relapse were assessed with the evaluation of CCECAI over time. One month after starting therapy, dogs with >25% CCECAI reduction were considered responders. During a three-month CCECAI evaluation as part of a twelve-month follow-up, a CCECAI >3 together with a ≥2 unit increase in responder dogs was considered a relapse. PLT and PLR displayed significant negative correlation with MPV. MPV was positively correlated with total protein and albumin levels and negatively correlated with CCECAI. Three dogs were classified as non-responders, and 14 relapsed within 12 months. No differences were observed in PLT, MPV, or PLR between responding/non-responding and relapsing/non-relapsing groups. PLT, MPV, and PLR correlated with total protein, albumin, and CCECAI, confirming PLT as a potential marker, and suggesting MPV as a new marker of clinical efficacy against canine IRE.     

Occurrence of Spontaneous Tumors in the Central Nervous System (CNS) of F344 and SD Rats

In order to accurately assess the carcinogenicity of chemicals with regard to rare tumors such as rat CNS tumors, sufficient information about spontaneous tumors are very important. This paper presents the data on the type, incidence and detected age of CNS tumors in F344/DuCrlCrlj (a total of 1363 males and 1363 females) and Crl:CD(SD) rats (a total of 1650 males and 1705 females) collected from in-house background data-collection studies and control groups of carcinogenicity studies at our laboratory, together with those previously reported in F344 and SD rats. The present data on F344/DuCrlCrlj rats (F344 rats) and Crl:CD(SD) rats (SD rats) clarified the following. (1) The incidences of all CNS tumors observed in F344 rats were less than 1%. (2) The incidences of malignant astrocytoma and granular cell tumor were higher in male SD rats than in female SD rats. (3) The incidences of astrocytoma and granular cell tumor were higher in SD rats than in F344 rats. (4) Among astrocytoma, oligodendroglioma and granular cell tumor, oligodendroglioma was detected at the youngest age, followed by astrocytoma, and ultimately, granular cell tumor developed in both strains. The incidences observed in our study were almost consistent with those previously reported in F344 and SD rats.     

The analysis—Hierarchical models: Past,present and future

This paper discusses statistical modelling for data with a hierarchical structure, and distinguishes in this context between three different meanings of the term hierarchical model: to account for clustering, to investigate variability and separate predictive equations at different hierarchical levels (multi-level analysis), and in a Bayesian framework to involve multiple layers of data or prior information. Within each of these areas, the paper reviews both past developments and the present state, and offers indications of future directions. In a worked example, previously reported data on piglet lameness are reanalyzed with multi-level methodology for survival analysis, leading to new insights into the data structure and predictor effects. In our view, hierarchical models of all three types discussed have much to offer for data analysis in veterinary epidemiology and other disciplines.     

Beneficial Biological Effects of Miso with Reference to Radiation Injury, Cancer and Hypertension

This review describes effects of miso with reference to prevention of radiation injury, cancer and hypertension with a twin focus on epidemiological and experimental evidence. Miso with a longer fermentation time increased crypt survival against radiation injury in mice. When evaluating different types of miso provided by different areas in Japan, miso fermented for a longer period increased the number of surviving crypts, and 180 days of fermentation was the most significant. Dietary administration of 180-day fermented miso inhibits the development of azoxymethane (AOM)-induced aberrant crypt foci (ACF) and rat colon cancers in F344 rats. Miso was also effective in suppression of lung tumors, breast tumors in rats and liver tumors in mice. The incidence of gastric tumors of groups of rats given NaCl was higher than those of the groups given miso fermented for longer periods. Moreover, the systolic blood pressure of the Dahl male rat on 2.3% NaCl was significantly increased but that of the SD rat was not. However, the blood pressures of the rats on a diet of miso or commercial control diet (MF) did not increase. Even though miso contains 2.3% NaCl, their blood pressures were as stable as those of rats fed commercial diet containing 0.3% salt. So we considered that sodium in miso might behave differently compared with NaCl alone. These biological effects might be caused by longer fermentation periods.     

Calvaria and orbital metastases of pulmonary adenosquamous carcinoma in a cat: a diagnostic challenge

An 11-year-old cat with a 4-month history of lethargy, inappetence, dysphagia, partial mandibular paralysis and weight loss, was euthanized due to the rapid deterioration of his condition. Post-mortem radiographic examination revealed severe bone lysis of the left zygomatic arch, temporal and parietal bones. Magnetic resonance imaging of the head showed a large isointense mass of the left side of the skull associated with extensive lysis of the parietal and temporal bones and destruction of the adjacent tympanic bulla. Gross and histological examinations revealed a pulmonary adenosquamous carcinoma of the left lung, with metastases to the spleen, liver, mesenteric lymph nodes, mesentery, diaphragm, abdominal aorta, left orbit and calvaria. No limb or digit metastases were detected.