BEVA primary care clinical guidelines: Diagnosis and management of equine pituitary pars intermedia dysfunction.

BACKGROUND: Pituitary pars intermedia dysfunction (PPID) is a prevalent, age-related chronic disorder in equids. Diagnosis of PPID can be challenging because of its broad spectrum of clinical presentations and disparate published diagnostic criteria, and there are limited available treatment options. OBJECTIVES: To develop evidence-based primary care guidelines for the diagnosis and treatment of equine PPID based on the available literature. STUDY DESIGN: Evidence-based clinical guideline using the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) framework. METHODS: Research questions were proposed by a panel of veterinarians and developed into PICO or another structured format. VetSRev and Veterinary Evidence were searched for evidence summaries, and systematic searches of the NCBI PubMed and CAB Direct databases were conducted using keyword searches in July 2022 and updated in January 2023. The evidence was evaluated using the GRADE framework. RESULTS AND RECOMMENDATIONS: The research questions were categorised into four areas: (A) Case selection for diagnostic testing, pre-test probability and diagnostic test accuracy, (B) interpretation of test results, (C) pharmacological treatments and other treatment/management options and (D) monitoring treated cases. Relevant veterinary publications were identified and assessed using the GRADE criteria. The results were developed into recommendations: (A) Case selection for diagnostic testing and diagnostic test accuracy: (i) The prevalence of PPID in equids aged ≥15 years is between 21% and 27%; (ii) hypertrichosis or delayed/incomplete hair coat shedding provides a high index of clinical suspicion for PPID; (iii) the combination of clinical signs and age informs the index of clinical suspicion prior to diagnostic testing; (iv) estimated pre-test probability of PPID should be considered in interpretation of diagnostic test results; (v) pre-test probability of PPID is low in equids aged <10 years; (vi) both pre-test probability of disease and season of testing have strong influence on the ability to diagnose PPID using basal adrenocorticotropic hormone (ACTH) or ACTH after thyrotropin-releasing hormone (TRH) stimulation. The overall diagnostic accuracy of basal ACTH concentrations for diagnosing PPID ranged between 88% and 92% in the autumn and 70% and 86% in the non-autumn, depending on the pre-test probability. Based on a single study, the overall diagnostic accuracy of ACTH concentrations in response to TRH after 30 minutes for diagnosing PPID ranged between 92% and 98% in the autumn and 90% and 94% in the non-autumn, depending on the pre-test probability. Thus, it should be remembered that the risk of a false positive result increases in situations where there is a low pre-test probability, which could mean that treatment is initiated for PPID without checking for a more likely alternative diagnosis. This could compromise horse welfare due to the commencement of lifelong therapy and/or failing to identify and treat an alternative potentially life-threatening condition. (B) Interpretation of diagnostic tests: (i) There is a significant effect of breed on plasma ACTH concentration, particularly in the autumn with markedly higher ACTH concentrations in some but not all 'thrifty' breeds; (ii) basal and/or post-TRH ACTH concentrations may also be affected by latitude/location, diet/feeding, coat colour, critical illness and trailer transport; (iii) mild pain is unlikely to have a large effect on basal ACTH, but caution may be required for more severe pain; (iv) determining diagnostic thresholds that allow for all possible contributory factors is not practical; therefore, the use of equivocal ranges is supported; (v) dynamic insulin testing and TRH stimulation testing may be combined, but TRH stimulation testing should not immediately follow an oral sugar test; (vi) equids with PPID and hyperinsulinaemia appear to be at higher risk of laminitis, but ACTH is not an independent predictor of laminitis risk. (C) Pharmacologic treatments and other treatment/management options: (i) Pergolide improves most clinical signs associated with PPID in the majority of affected animals; (ii) Pergolide treatment lowers basal ACTH concentrations and improves the ACTH response to TRH in many animals, but measures of insulin dysregulation (ID) are not altered in most cases; (iii) chasteberry has no effect on ACTH concentrations and there is no benefit to adding chasteberry to pergolide therapy; (iv) combination of cyproheptadine with pergolide is not superior to pergolide alone; (v) there is no evidence that pergolide has adverse cardiac effects in horses; (vi) Pergolide does not affect insulin sensitivity. (D) Monitoring pergolide-treated cases: (i) Hormone assays provide a crude indication of pituitary control in response to pergolide therapy, however it is unknown whether monitoring of ACTH concentrations and titrating of pergolide doses accordingly is associated with improved endocrinological or clinical outcome; (ii) it is unknown whether monitoring the ACTH response to TRH or clinical signs is associated with an improved outcome; (iii) there is very weak evidence to suggest that increasing pergolide dose in autumn months may be beneficial; (iv) there is little advantage in waiting for more than a month to perform follow-up endocrine testing following initiation of pergolide therapy; there may be merit in performing repeat tests sooner; (v) timing of sampling in relation to pergolide dosing does not confound measurement of ACTH concentration; (vi) there is no evidence that making changes after interpretation of ACTH concentrations measured at certain times of the year is associated with improved outcomes; (vii) evidence is very limited, however, compliance with PPID treatment appears to be poor and it is unclear whether this influences clinical outcome; (viii) evidence is very limited, but horses with clinical signs of PPID are likely to shed more nematode eggs than horses without clinical signs of PPID; it is unclear whether this results in an increased risk of parasitic disease or whether there is a need for more frequent assessment of faecal worm egg counts. MAIN LIMITATIONS: Limited relevant publications in the veterinary scientific literature. CONCLUSIONS: These findings should be used to inform decision-making in equine primary care practice.

Ex vivo biomechanical evaluation of an adhered fiberglass and polymethyl methacrylate sole-hoof wall cast on stabilization of type III distal phalanx fractures under simulated physiologic midstance loads.

OBJECTIVE: To evaluate the effect of the application of a novel fiberglass-glue cast (FGC) on the fracture gap width in experimentally created type III distal phalanx fractures in cadaveric specimens under simulated physiologic loads. STUDY DESIGN: Ex vivo biomechanical laboratory study. ANIMALS: Nine unilateral adult equine cadaver forelimbs. METHODS: Type III distal phalanx fractures were created in forelimb specimens, which maintained distal components of the passive stay apparatus. The fracture gap was measured at 5%, 20%, 25%, 50%, 75%, and 95% of fracture length (palmar articular border to solar margin) using D65Pr-PaDiO radiographs. The limb was axially loaded (700, 3600, 4600, and 6700 N) before, during, and after removal of a woven fiberglass cloth and polymethyl methacrylate cast that encompassed the sole and distal portion of the hoof wall (FGC). Fracture gap widths were compared among loads and treatments using a mixed model ANOVA. RESULTS: On average, under simulated physiological midstance loads, the fracture gap width was 0.2 mm smaller after FGC application, with the greatest decrease (0.5 mm) near the articular surface. On average, it was 0.3 mm smaller than after FGC removal. Fracture gap width was 0.1 mm greater when midstance loads transitioned from standing load to walking, trotting, and gallop loads. The fracture gap width increased by 1.3 mm with increasing distance from the articular surface. CONCLUSION: The FGC reduced the fracture gap width and prevented the fracture gap widening that occurred after FGC removal. CLINICAL SIGNIFICANCE: The findings support consideration of FGC use in the treatment of horses with type III distal phalangeal fractures.

Treatment of Naturally Occurring Tendon Disease with Allogeneic Multipotent Mesenchymal Stromal Cells: A Randomized, Controlled, Triple-Blinded Pilot Study in Horses.

The treatment of tendinopathies with multipotent mesenchymal stromal cells (MSCs) is a promising option in equine and human medicine. However, conclusive clinical evidence is lacking. The purpose of this study was to gain insight into clinical treatment efficacy and to identify suitable outcome measures for larger clinical studies. Fifteen horses with early naturally occurring tendon disease were assigned to intralesional treatment with allogeneic adipose-derived MSCs suspended in serum or with serum alone through block randomization (dosage adapted to lesion size). Clinicians and horse owners remained blinded to the treatment during 12 months (seven horses per group) and 18 months (seven MSC-group and five control-group horses) of follow-up including clinical examinations and diagnostic imaging. Clinical inflammation, lameness, and ultrasonography scores improved more over time in the MSC group. The lameness score difference significantly improved in the MSC group compared with the control group after 6 months. In the MSC group, five out of the seven horses were free of re-injuries and back to training until 12 and 18 months. In the control group, three out of the seven horses were free of re-injuries until 12 months. These results suggest that MSCs are effective for the treatment of early-phase tendon disease and provide a basis for a larger controlled study.

Equine conjunctival haemangiosarcoma: Clinical presentation, management, and outcome of seven cases in the United Kingdom.

Background: Only 27 cases of equine conjunctival haemangiosarcoma have been reported in the literature over the past 37 years. Out of these, 22% of cases were lost to follow-up, 52% were euthanized, and 26% survived. A scarcity of cases and information is available for this rarely seen conjunctival tumour. Aim: To describe the clinical features, management, and outcome of conjunctival hemangiosarcoma in seven horses in the UK. Methods: Optivet medical records were reviewed for equine cases seen or advised on with a histopathological diagnosis of conjunctival haemangiosarcoma between January 2013 and March 2023. Medical records were accessed for details of signalment, history, management, and follow-up. Histopathology was used to confirm the diagnosis of haemangiosarcoma and assess the surgical margins. Immunohistochemistry was performed in a minority of cases with poorly differentiated solid tumours to support vascular lineage. Results: Seven eyes from seven horses (five geldings and two mares) with a mean age of 16 years and median of 18 years (range 10-21 years) met the criteria. Serosanguinous discharge was seen in six eyes. All eyes were managed surgically; 4 by exenteration and 3 by conjunctivectomy/keratectomy. Adjunctive cryotherapy was performed in two eyes. Metastatic disease in the ipsilateral parotid salivary gland, confirmed with histopathology, was seen in one horse. Surgical margins were clear in all but one eye. Solar elastosis was noted in five eyes. All horses were healthy at the last follow-up (0.2-5 years, mean 2.9 years, and median 2 years). Conclusion: Equine conjunctival haemangiosarcoma is rare. Serosanguinous ocular discharge is a common clinical sign. Early surgical excision is highly effective. Solar elastosis is a common histopathological feature, suggesting a role for UV-light in the pathogenesis.

Fecal microbiota transplant for treatment of diarrhea in adult hospitalized horses-111 cases (2013-2018).

Background: Fecal microbiota transplant (FMT) is increasingly administered as part of the treatment of colitis in horses, yet there is little data as to its effectiveness. Aim: Retrospective evaluation of the effects of FMT on discharge status, fecal consistency, length of hospitalization, and improvement in clinical signs in horses hospitalized for diarrhea. Methods: Retrospective case-control study. Medical records of adult horses (>1 year old) that received at least one transfaunation treatment (2013-2018) in two referral hospitals were identified through a medical records database search. Medical records of contemporary adult horses with diarrhea who did not receive FMT at the same study centers were used as controls. Results: Control horses had statistically significant shorter hospitalization [7 (1-21)] as compared to the transfaunation group [12 (3-31)] ( p = 0.0006). There were no significant differences between groups in the number of days to the improvement of feces (p = 0.38), or in days to normalization of fecal consistency (p = 0.43), respiratory rate (p = 0.42), heart rate (p = 0.27), body temperature (p = 0.12), peripheral white blood cell count (p = 0.37), improvement in appetite (p = 0.81), or attitude (p = 0.06). There was also no significant difference in survival to discharge (transfaunation 28/37, 75.7%; control 56/74, 75.7%, p = 1.0). Conclusion: There were no significant advantages of performing FMTs in horses with diarrhea in this retrospective study. This highlights the need for prospective, randomized studies to evaluate the efficacy of FMT, as well as different formulations, in horses with colitis before this can become standard practice.

Advances in dental management in the equine geriatric patient: strategies for improved welfare.

Geriatric horses have a high prevalence of dental disease, which is a culmination of age-related dental changes and dental disease throughout the life of the horse that may have long-term consequences. Wear abnormalities, diastemata with periodontal disease, pulpitis and endodontic disease, infundibular caries, and equine odontoclastic tooth resorption and hypercementosis become more prevalent with age. Recognition of age-related dental disease at an early stage can help to treat and possibly preserve teeth for longer. With a natural decrease in masticatory efficiency, it is even more important to preserve teeth where possible and prevent any painful dental disease. Regular routine dental examination and maintenance will help to prevent many dental conditions such as wear disorders and possibly secondary diastemata. Successful treatment and management of most dental diseases are possible even in older patients and will ensure that we are able to maintain a high standard of welfare as horses age.

Distribution of equine and food animal emergency caseload by time of day, day of week, time of year, holiday, and phase of moon at an academic ambulatory and referral hospital.

OBJECTIVE: Determine the association of time of day, day of week, time of year, holiday, and phase of moon on academic ambulatory and hospital emergency caseload for equine and food animal species. DESIGN: Retrospective study. SETTING: Large animal teaching hospital emergency service. ANIMALS: Equine and food animals. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: The hospital database was searched for after-hours on-farm and in-hospital emergencies seen from 2014 to 2020. Variables included date and time of admission, species (equine or food/fiber animal [FA]), and hospital service (field or in-hospital). The association of the caseload with time of day, day of week, day of year (holiday, full moon, or new moon), and season of year was defined and examined. The majority of equine field-based emergencies occurred on the weekend, in contrast to 44.8% of hospital cases. Most equine emergencies occurred between 4:00 p.m. and midnight on weekdays and between 8:00 a.m. and 4:00 p.m. on weekends for both field (89.1% and 46.9%) and hospital (82.8% and 48%) services. The same was true for FA cases on the farm (90% and 49.2%) and in the hospital (85% and 51.4%). More equine cases (67%) were seen in the field than FA. Winter had the fewest emergency cases for all species and locations, and spring had the most for FA. The majority of holiday equine emergencies were seen in the field (62.2%), but the majority of holiday FA emergencies were seen in the hospital (66.3%). Moon phase had no significance on caseload for all species and locations. CONCLUSIONS: Saturdays and Sundays were the busiest days for all species and services. Winter was the slowest time for emergencies for all species and services. Most emergencies were seen between 4:00 p.m. and midnight on weekdays and between 8:00 a.m. and 4:00 p.m. on Sundays and Saturdays.

Efficacy Evaluation of a Commercial Formulation With Duddingtonia Flagrans in Equine Gastrointestinal Nematodes.

The indiscriminate use of antiparasitics for the treatment of helminths in horses has caused the ineffectiveness of commonly used chemical active principles, therefore, new alternatives such as the use of helminthophagous fungi have been studied. In this context, this study aimed to evaluate the in vitro efficacy of the commercial formulation Bioverm, composed of the fungus Duddingtonia flagrans strain AC001, in the reduction of gastrointestinal nematode larvae in equine feces. In coproculture, the genus Cyathostomum sp. was the most prevalent in the analyzed samples. The commercial formulation with D. flagrans demonstrated effectiveness in the predation of Cyathostomum sp. in tests. The recommended dose of 0.4 g, containing 105 chlamydospores per gram of product, reduced larvae by 44.23%, while the extrapolated dose of 1.0 g with the same concentrations of chlamydospores (105/g) resulted in a reduction of 57.20%, indicating the effectiveness of the product in controlling infective larvae.

Introduction to Equine Biologic and Regenerative Therapies.

Regenerative medicine is defined as the process of replacing or regenerating cells, tissues, or organs to restore or establish normal function. The use of regenerative medicine in equine practice to treat injured musculoskeletal tissues with limited capacity for intrinsic healing is growing. This article provides the practitioner with a brief and basic overview of the regenerative products currently used in equine practice.

Overview of Equine Stem Cells: Sources, Practices, and Potential Safety Concerns.

Over the past 2 decades, equine veterinarians are turning increasingly to stem cell therapies to repair damaged tissues or to promote healing through modulation of the immune system. Research is ongoing into optimizing practices associated with stem cell product transport, dosage, and administration. Culture-expanded equine mesenchymal stem cell therapies seem safe, even when used allogeneically, but various safety concerns should be considered. Stem cells and cellular reprogramming tools hold great promise for future equine therapies.

Use of Stem Cells for the Treatment of Musculoskeletal Injuries in Horses.

Mesenchymal stem cells (MSCs) are used as a regenerative therapy in horses for musculoskeletal injury since the late 1990s and in some regions are standard of care for certain injuries. Yet, there is no Food and Drug Administration-approved MSC therapeutic in the United States for horses. In humans, lack of regulatory approval in the United States has been caused by failure of late-phase clinical trials to demonstrate consistent efficacy, perhaps because of nonuniformity of MSC preparation and application techniques. This article discusses clinical evidence for musculoskeletal applications of MSCs in the horse and current challenges to marketing approval.

Equine Autologous Conditioned Serum and Autologous Protein Solution.

Orthobiologics are used with increasing frequency in equine musculoskeletal disease to improve the quality of the repair tissue and prevent reinjury. Autologous blood-based products, or hemoderivatives, are made by processing the patient's blood using different systems to produce a final therapeutic product. Autologous conditioned serum (ACS) and autologous protein solution (APS) are commonly used to treat joint disorders and can also be used treat tendon and ligament injuries. Hemoderivatives contain increased concentrations of anti-inflammatory and immunomodulatory cytokines, and growth factors that help direct tissue healing and repair. The specifics of ACS and APS for treatment of musculoskeletal injuries are discussed.

Use of Biologics and Stem Cells in the Treatment of Other Inflammatory Diseases in the Horse.

Mesenchymal stem cells (MSCs) are powerful immunomodulatory cells that act via multiple mechanisms to coordinate, inhibit, and control the cells of the immune system. MSCs act as rescuers for various damaged or degenerated cells of the body via (1) cytokines, growth factors, and signaling molecules; (2) extracellular vesicle (exosome) signaling; and (3) direct donation of mitochondria. Several studies evaluating the efficacy of MSCs have used MSCs grown using xenogeneic media, which may reduce or eliminate efficacy. Although more research is needed to optimize the anti-inflammatory potential of MSCs, there is ample evidence that MSC therapeutics are worthy of further development.

Equine Platelet-Rich Plasma.

Platelet-rich plasma (PRP) is an orthobiologic therapy composed of platelets, leukocytes, red blood cells, and plasma proteins. PRP has been used for 20 years, but progress determining efficacy has been slow. The definitions and classification of PRP are reviewed, and the use of PRP for tendon, ligament, and joint disease is discussed with a focus on findings of basic science and clinical studies, platelet activation, concurrent administration of nonsteroidal anti-inflammatory drugs, and treatment complications. Finally, the advantages of platelet lysates and freeze-dried platelets are discussed. The promising results of a PRP lysate optimized for antibiofilm and antimicrobial properties are introduced.

Advances in Regional Vascular Injection Techniques for the Delivery of Stem Cells to Musculoskeletal Injury Sites.

Vascular injections of stem cells are a pertinent alternative to direct intralesional injections when treating multiple or extensive lesions or with lesions impossible to reach directly. Extensive research using stem cell tracking has shown that intra-arterial injections without the use of a tourniquet should be preferred over venous or arterial regional limb perfusion techniques using a tourniquet. The median artery is used for the front limbs and the cranial tibial artery for the hind limbs. Proper efficacy studies are still lacking but early clinical work seems promising.

Advances in Imaging Techniques to Guide Therapies and Monitor Response to the Treatment of Musculoskeletal Injuries.

Continual advancements in diagnostic imaging have allowed for more accurate and complete diagnoses of injuries in the performance horse. The use of several different imaging tools has further allowed the equine sports medicine clinician to more carefully direct treatment options, monitor response to therapy and guide rehabilitation recommendations. The advancements in diagnostic imaging and novel treatment options have led to the improvement in the overall prognosis of many injuries that affect the horse and their performance. The purpose of this section is to review the advancements made in diagnostic imaging of the horse and to aid the practitioner in the selection of the appropriate modality and how best to use them to guide treatment and monitoring decisions.