Unilateral laser ventriculocordectomy results in increased arytenoid stability in horses with severe left sided recurrent laryngeal neuropathy.

BACKGROUND: There is no objective information reporting the effect of unilateral laser ventriculocordectomy (VeC) on arytenoid abduction or stability. OBJECTIVES: To evaluate arytenoid stability and abduction in horses with severe recurrent laryngeal neuropathy (RLN) before and after unilateral laser VeC. STUDY DESIGN: Prospective cohort. METHODS: Eight horses with grade C or D exercising laryngeal function that underwent unilateral laser VeC were included. Exercising endoscopy was performed before and ≥6 weeks after left-sided laser VeC. Arytenoid stability at maximal exercise was calculated by measuring the left-to-right quotient angle ratio (LRQ) of the corniculate processes at the points of maximal arytenoid abduction (expiration) and maximal arytenoid collapse (inspiration). For each horse, means of measurements obtained for four breaths pre- and post-operatively were used for statistical analysis. RESULTS: The difference in LRQ between inspiration and expiration was lower post-operatively (median 0.039; interquartile range [IQR] 0.032-0.047) compared with pre-operatively (median 0.158; IQR 0.083-0.249; p = 0.01) confirming the left arytenoid was more stable following unilateral laser VeC. The degree of improvement was significantly greater for grade D horses compared with grade C horses (p = 0.04). The LRQ measured on maximal abduction was also lower post-operatively (median 0.467; IQR 0.444-0.506) compared with pre-operatively (median 0.578; IQR 0.554-0.655; p = 0.02) indicating the left arytenoid was less abducted following surgery. MAIN LIMITATIONS: The sample size was small, no racehorses were included and post-operative assessment was conducted at a variable time after surgery. CONCLUSION: Unilateral laser VeC in grade C and D RLN-affected horses results in slightly reduced left arytenoid abduction but increased arytenoid stability.

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.

Diagnosis of equine pituitary pars intermedia dysfunction.

Equine pituitary pars intermedia dysfunction (PPID) is common in aged horses. The majority of horses respond well to treatment, but treatment is lifelong, meaning accurate diagnosis of PPID is important. Similar to any condition, there is no perfect laboratory test to diagnose PPID and accuracy is affected by the characteristics of the population in which the test is being evaluated. This review details the importance of consideration of clinical factors and diagnostic test accuracy. Basal adrenocorticotrophic hormone (ACTH) concentration is used most frequently in practice and has very good diagnostic accuracy when used in combination with clinical judgement and the correct application of diagnostic thresholds. The thyrotropin-releasing hormone stimulation test can be used in horses with equivocal test results following basal ACTH testing, or to evaluate subtle cases due to its improved accuracy.

Equine Endocrine Disease: Challenges With Case Definition for Research.

Equine endocrine disease is an important area for equine research, requiring an appropriate case definition for inclusion and criteria for exclusion from disease. Defining a case for research may be different from criteria for clinical diagnosis. Further, clinical diagnosis recommendations have been changing regularly, making this area challenging for equine scientists. This review discusses the diagnosis of major equine endocrine diseases, pituitary pars intermedia dysfunction, equine metabolic syndrome and insulin dysregulation, focusing on the most appropriate diagnostic methods for research case definitions. Different diagnostic methods, including use of reference intervals and clinical decision limits, will be discussed with their relative merits for use in case definition for research.

Equine pituitary pars intermedia dysfunction: Identifying research priorities for diagnosis, treatment and prognosis through a priority setting partnership.

Pituitary pars intermedia dysfunction (PPID) is the most prevalent endocrine disorder of older equids. To date, key research areas likely to have the greatest impact on equine health have not been identified. In human medicine, public and patient involvement is widely used to inform research agendas. This study aimed to engage with veterinary surgeons and horse owners to identify evidence gaps ('uncertainties') and prioritise these into a list of the 10 most important PPID research questions. The James Lind Alliance (JLA) Priority Setting Partnership (PSP) Framework was adapted. Questions about the diagnosis, treatment and prognosis of PPID were gathered via an online survey targeting veterinary surgeons and horse owners with experience of PPID. Thematic analysis was used to form a longlist of collated indicative research questions (CIRQs), defined by the JLA as true 'evidence uncertainties' when not answered by a published, clinically relevant, up-to-date systematic review. In an interim prioritisation survey, questions were ranked by weighted scores creating a shortlist of 25 that were taken forward to the PSP workshop, where participants reached a consensus on the top 10. Useable responses containing ≥1 question were received from 524 respondents (92.6% owners, n = 485; 7.4% veterinary surgeons, n = 39). After screening for relevance, 1,260 individual questions were included in thematic analysis, resulting in 47 CIRQs. Interim prioritisation votes for the CIRQs were received from 360 respondents. The top 10 questions prioritised at the PSP workshop focused on long-term prognosis, diagnostic accuracy, efficacy of pergolide treatment, alternative treatment/management strategies and potential treatment options for poor responders to pergolide. The quantity of questions generated indicates an extensive number of uncertainties regarding the diagnosis, treatment and prognosis of PPID. The top 10 research questions will help to inform key areas for evidence synthesis and knowledge translation, and to direct future research into areas most important to end users involved in caring for and treating animals with PPID.

Relationships of inflamm-aging with circulating nutrient levels, body composition, age, and pituitary pars intermedia dysfunction in a senior horse population.

Similarly to aged humans, senior horses (≥20 years) exhibit chronic low-grade inflammation systemically, known as inflamm-aging. Inflamm-aging in the senior horse has been characterized by increased circulating inflammatory cytokines as well as increased inflammatory cytokine production by lymphocytes and monocytes in response to a mitogen. Little is currently known regarding underlying causes of inflamm-aging. However, senior horses are also known to present with muscle wasting and often the endocrinopathy pituitary pars intermedia dysfunction (PPID). Despite the concurrence of these phenomena, the relationships inflamm-aging may have with measures of body composition and pituitary function in the horse remain unknown. Furthermore, nutrition has been a focus of research in an attempt to promote health span as well as life span in senior horses, with some nutrients, such as omega-3 fatty acids, having known anti-inflammatory effects. Thus, an exploratory study of a population of n = 42 similarly-managed senior horses was conducted to determine relationships between inflamm-aging and measures of circulating nutrients, body composition, age, and PPID. Serum was collected to determine vitamin, mineral, and fatty acid content. Peripheral blood mononuclear cells were also isolated to determine inflammatory cytokine production of interferon-γ (IFN-γ) and tumor necrosis factor-α (TNF-α) following stimulation with a mitogen, as well as to determine gene expression of interleukin(IL)-1ß, IL-6, IL-10, IFN-γ, and TNF-α. Serum IL-6 and C-reactive protein were determined by enzyme-linked immunosorbent assay. Whole blood was collected for hematological and biochemical analysis. Body composition was evaluated via ultrasound and muscle scoring for all 42 horses as well as by deuterium oxide dilution for a subset of n = 10 horses. Pituitary function was evaluated by measuring basal adrenocorticotropin hormone concentrations as well as by thyrotropin releasing hormone stimulation testing (to determine PPID status). Results showed various relationships between inflammatory markers and the other variables measured. Most notably, docosadienoic acid (C22:2n6c), docosapentaenoic acid (C22:5n3c), and folate were positively associated with numerous inflammatory parameters (P ≤ 0.05). Although no relationships were found between inflamm-aging and PPID, being positive for PPID was negatively associated with vitamin B12 (P ≤ 0.01). No relationships between inflammation and body composition were found. Even within this senior horse population, age was associated with multiple parameters, particularly with numerous inflammatory cytokines and fatty acids. In summary, inflamm-aging exhibited relationships with various other parameters examined, particularly with certain fatty acids. This exploratory study provides insights into physiological changes associated with inflamm-aging in the senior horse.