HummingFlow: novel single twist-drill access for ventricular drainage, irrigation, monitoring, and automated local drug delivery in subarachnoid hemorrhage.

OBJECTIVE: The management of delayed cerebral ischemia after aneurysmal subarachnoid hemorrhage (aSAH) remains one of the most important targets for neurocritical care. Advances in monitoring technology have facilitated a more thorough understanding of the pathophysiology and therapeutic approaches, but interventions are generally limited to either systemic therapies or passive CSF drainage. The authors present a novel approach that combines a multimodal monitoring bolt-based system with an irrigating ventricular drain capable of delivering intrathecal medications and describe their early experience in patients with aSAH. METHODS: The authors performed a retrospective review of cases treated with the combined Hummingbird multimodal bolt system and the IRRAflow irrigating ventriculostomy. RESULTS: Nine patients were treated with the combined multimodal bolt system with irrigating ventriculostomy approach. The median number of days to clearance of the third and fourth ventricles was 3 days in patients with obstructive intraventricular hemorrhage. Two patients received intrathecal alteplase for intraventricular hemorrhage clearance, and 2 patients received intrathecal nicardipine as rescue therapy for severe symptomatic angiographic vasospasm. CONCLUSIONS: Combined CSF drainage, irrigation, multimodality monitoring, and automated local drug delivery are feasible using a single twist-drill hole device. Further investigation of irrigation settings and treatment approaches in high-risk cases is warranted.

Multivariable analysis to determine risk factors associated with abortion in mares.

Risk factors associated with equine reproductive efficiency have been identified along with those associated specifically with early pregnancy loss (EPL). In contrast, no studies have reported risk factors associated with abortion (loss between day 70 and 300 post-cover). Given the causes of abortion differ to those of EPL, likely too will the risk factors. A retrospective cohort study was carried out to identify risk factors associated with abortion in UK and Irish based Thoroughbreds, collecting data on 20 exposure variables over a five-year period. A generalized linear mixed model was utilized to evaluate the associations between exposure variables and abortion, with clustering of observations accounted for at the mare and farm level. Variables with a likelihood ratio test (LRT) p value <0.2 were entered into the model in a forward stepwise approach. Pregnancy outcome was available on 4,439 pregnancies from 2,510 mares. Having had two or more prior abortions (odds ratio (OR) 7.91, 95% confidence interval (CI) 2.86, 21.88), conceiving on the second or subsequent covered estrous cycle (OR 1.84, 95% CI 1.22, 2.78) and conceiving multiple conceptuses (OR 1.68, 95% CI 1.02, 2.76) were associated with an increased risk of abortion compared to null parous, first estrous cycle covers and singleton conceptions respectively. Increasing paternal age (OR 0.95, 95% CI 0.90, 0.99) was associated with a decreasing risk of abortion. Mare and farm variance were not significant in the final model, LRT p=0.43. These findings provide evidence-based data to inform Thoroughbred breeding management practices to help mitigate abortion risk.

Mixed-Effects Modelling of the Risk Factors Associated with Multiple Pregnancies in Thoroughbred Mares.

Multiple pregnancies (MPs) are commonly diagnosed during breeding management of mares. Whilst some studies have reported on factors associated with the risk of MPs, few have utilised multivariable data analysis to control for confounding variables. A prospective cohort study of Thoroughbred broodmares was conducted with information collected on 27 factors. Mixed-effects logistic regression was used to determine risk factors for MPs. Mare, stallion, stud, and veterinarian were evaluated as random effects. The prevalence of MPs in 1754 mares and 2245 pregnancies was 16.06% (95% confidence interval [CI] = 14.54, 17.58). Multiple ovulations (OR = 15.57, 95% CI = 11.88, 20.53) and treatment with cloprostenol (OR = 1.35, 95% CI = 1.015, 1.80) were associated with increased odds of MPs following multivariable analysis. Mares that foaled at the start of the breeding season (OR = 0.66, 95% CI = 0.47, 0.94), conceived at the second or more oestrus cycles (OR = 0.60, 95% CI= 0.43, 0.84), or identified with a uterine cyst (OR = 0.63, 95% CI = 0.40, 0.97) were at reduced odds of conceiving MPs. Mare, stallion, stud, and veterinarian were not associated with MPs. These findings provide possible explanations as to why the prevalence of MPs but not MOs have increased over the last decade.

Lethal variants of equine pregnancy: is it the placenta or foetus leading the conceptus in the wrong direction?

Embryonic and foetal loss remain one of the greatest challenges in equine reproductive health with 5-10% of established day 15 pregnancies and a further 5-10% of day 70 pregnancies failing to produce a viable foal. The underlying reason for these losses is variable but ultimately most cases will be attributed to pathologies of the environment of the developing embryo and later foetus, or a defect intrinsic to the embryo itself that leads to lethality at any stage of gestation right up to birth. Historically, much research has focused on the maternal endometrium, endocrine and immune responses in pregnancy and pregnancy loss, as well as infectious agents such as pathogens, and until recently very little was known about the both small and large genetic variants associated with reduced foetal viability in the horse. In this review, we first introduce key aspects of equine placental and foetal development. We then discuss incidence, risk factors and causes of pregnancy loss, with the latter focusing on genetic variants described to date that can impact equine foetal viability.

First reported case of fragile foal syndrome type 1 in the Thoroughbred caused by PLOD1 c.2032G>A.

BACKGROUND: Warmblood Fragile Foal Syndrome Type 1 (WFFS) is an autosomal recessive disorder reported previously only in warmbloods and thought to be caused by a variant in the gene procollagen-lysine,2-oxoglutarate 5-dioxygenase 1 (PLOD1, c.2032G>A, p.Gly678Arg). Given the presentation of this Thoroughbred case, we hypothesised that a similar genetic mechanism caused this phenotype. OBJECTIVES: To describe the pathological and genetic findings on a foal presenting to a veterinary practice in the UK with skin lesions similar to other Ehlers-Danlos Syndromes, including those documented for warmbloods with WFFS. STUDY DESIGN: A single case report describing a genetic investigation. METHODS: A Thoroughbred foal presenting as dystocia was euthanised for multiple skin lesions and developmental abnormalities. DNA extracted from the foal was tested for the PLOD1 variant (c.2032G>A, p.Gly678Arg) using the commercially available assay. To confirm causality and further interrogate potential novel causes of Ehlers-Danlos Syndrome, 1799 functional candidate genes, including PLOD1, were analysed using whole genome sequencing data generated from DNA extracted from the foal's muscle. These data were compared to 34 control samples from at least 11 other breeds. Variants were prioritised for further evaluation based on predicted impact on protein function. RESULTS: Post-mortem evaluation concluded that this foal suffered from a condition of collagen dysplasia. The foal was homozygous for the c.2032G>A PLOD1 variant. Only two other missense variants identified from whole genome sequencing data were also computationally predicted to be deleterious to protein function, (NPHP3 c.1253T>C, p.Leu418Pro, EPDR1 c.154G>C, p.Glu52Gln). Neither of these genes have been linked to similar phenotypes, or Ehlers-Danlos Syndrome in humans or other species and thus further investigation of these variants as the cause of EDS was not warranted. MAIN LIMITATIONS: This study is a single case report in the Thoroughbred with no additional cases from this breed yet identified to replicate this finding. CONCLUSIONS: Given the clinical presentation similar to WFFS, homozygosity for the PLOD1 variant, and absence of another more plausible causal variant from the WGS experiment, we conclude that PLOD1 c.2032G>A is the likely cause of this foal's condition. This is the first documented evidence of fragile foal syndrome caused by the PLOD1 variant in a breed outside of warmbloods, the Thoroughbred. We therefore recommend a change in the name of this disorder to fragile foal syndrome type 1 (FFS) and utilisation of genetic testing in Thoroughbreds to avoid producing affected foals.

Incidence and causes of pregnancy loss after Day 70 of gestation in Thoroughbreds.

BACKGROUND: Pregnancy loss after Day 70 of gestation manifests as abortion, stillbirth or perinatal death. While previous studies have reported the diagnoses of laboratory submissions, none have quantified the incidence and causes of abortions, stillbirths and perinatal mortality at a population level. OBJECTIVES: To report the incidence and causes of pregnancy loss after Day 70 of gestation in a cohort of Thoroughbreds. STUDY DESIGN: Retrospective cohort study. METHODS: Outcomes of Day 70 pregnancies were collected from eight Thoroughbred farms over the 2013-2017 breeding seasons. Stud, veterinary and laboratory records were supplemented with publicly available data. Cause of loss was categorised using custom criteria. RESULTS: Data were collected on 3,586 pregnancies from 1,802 mares. The incidence risk of a pregnancy failing to produce a live foal at 24 hours post parturition was 7.3% (95% confidence interval (CI) 6.5-8.2, equating to 7.3 cases per 100 Day-70 pregnancies). The incidence of pregnancy loss between Day 70 and 300 of gestation, Day 301-315 and stillbirth/perinatal death was 4.0% (95% CI 3.4-4.7), 0.3% (95% CI 0.2-0.6) and 1.4% (95% CI 1.1-1.9) respectively. Of the pregnancy losses where tissue was available, 61.1% were submitted for post-mortem examination. The incidence risk of loss due to umbilical cord-related pathologies was 1.5% (95% CI 1.1-1.9), 0.4% (95% CI 0.2-0.6) for noninfectious placental disease and 0.3% (95% CI 0.2-0.6) for both infectious placentitis and Equine Herpesvirus infection. No primary diagnosis was made in 11.2% of the cases which underwent full post-mortem examination. MAIN LIMITATIONS: It was not possible to differentiate between intra-partum stillbirth and early post-partum death. CONCLUSION: Pregnancy loss after Day 70 of gestation is a significant source of loss in the Thoroughbred with umbilical cord-related pathologies being the most commonly diagnosed cause. Reporting the incidence of pregnancy loss at a population level with clear case definitions will allow for accurate global comparisons.