Efficacy of Bravecto® Plus spot-on solution for cats (280 mg/ml fluralaner and 14 mg/ml moxidectin) in the prevention of feline Aelurostrongylus abstrusus infection evaluated in a multi-diagnostic approach.

BACKGROUND: Aelurostrongylus abstrusus is one of the most important respiratory nematodes of felines. Infections may lead to respiratory clinical signs with varying severity or even death, emphasizing the need for preventive treatment of cats with outdoor access to circumvent patent infections. METHODS: Therefore, the preventive efficacy of a spot-on formulation of 280 mg/ml fluralaner and 14 mg/ml moxidectin (Bravecto® Plus spot-on solution for cats, MSD) against A. abstrusus was evaluated in a negative controlled, randomized and partially blinded efficacy study with 28 purpose-bred cats in a non-terminal design. In three different treatment regimes, the minimum recommended dose of 40 mg fluralaner and 2.0 mg moxidectin/kg bodyweight (BW) was administered once at 12, 8 or 4 weeks (study group G1, G2 and G3, respectively) prior to experimental infection with 300 third-stage A. abstrusus larvae, while G4 served as placebo-treated control. RESULTS: From 30 to 46 days post infection (dpi; SD 114 to 130), faeces were sampled to monitor first-stage larvae (L1) excretion for efficacy determination. Secondary efficacy criteria, including respiratory parameters, serological antibody levels and computed tomography (CT) findings, were assessed once before enrolment (SD -7 to -1) and before infection (SD 75 to 83). After infection, CT evaluation was performed once at 47-50 dpi (SD 131 to 134), and respiratory parameters and antibody levels were regularly assessed twice or once a week, respectively (1 up to 78 dpi, SD 85 up to 162). All animals in the control group excreted L1 by 33-37 dpi and remained positive throughout the study period from 41 to 46 dpi (SD 125 to 130). In the treatment groups, only one animal each of G1 and G2 excreted L1 at two consecutive days, and four cats of G1, two of G2 and three of G3 were positive on single occasions. While the geometric mean (GM) of the maximum number of excreted L1 per 5 g of faeces was 7380.89 in the control group (G4), GMs were significantly lower in the treatment groups with 1.63 in G1, 1.37 in G2 and 0.79 in G3. Thus, based on GMs, the reduction in excreted L1 exceeded 99.9% in all three treatment groups. Based on CT severity scores, all lungs of the animals of the control group showed severe pulmonary changes post infection, whereas lungs of the cats of the treatment groups were either unaltered (4 animals), mildly (11 animals), or moderately altered (5 animals). Moreover, seroconversion was observed in all cats of the control group, but not in those of the treatment groups. CONCLUSIONS: The combination of diagnostic methods used in this non-terminal study yielded coherent and reliable results. A single administration of Bravecto® Plus spot-on solution for cats was well tolerated and effective in the prevention of aelurostrongylosis for at least 12 weeks.

[Macrophthalmos mimics microphthalmos in an 8-month-old Great Swiss Mountain Dog]. / Makrophthalmus imitiert Mikrophthalmus bei einem 8 Monate alten Großen Schweizer Sennenhund.

An 8-month-old Great Swiss Mountain dog was presented with a suspected right-sided microphthalmos, malformed and blind globe which was present since birth. On magnetic resonance imaging an ellipsoid macrophthalmos with absence of the normal retrobulbar tissue was detected. Histology revealed a dysplastic uvea with unilateral cyst formation associated with mild lymphohistiocytic inflammation. The ciliary body covered the posterior side of the lens unilaterally and showed focal metaplastic bone formation. Slight cataract formation as well as diffuse panretinal atrophy and intravitreal retinal detachment was evident. Preoperative diagnostic imaging procedure is recommended in eyes that clinically demonstrate as microphthalmos and are planned to be enucleated. As described in this case report the bulbus may be macrophthalmic which potentially complicates the enucleation. The performance of such a procedure at a site with ophthalmologic and soft tissue expertise is advisable. To the authors' knowledge this is the first report of a macrophthalmos with multiple ocular defects in a dog.

Methods of Radiographic Measurements of Heart and Left Atrial Size in Dogs with and without Myxomatous Mitral Valve Disease: Intra- and Interobserver Agreement and Practicability of Different Methods.

Dogs suffering from Myxomatous Mitral Valve Disease (MMVD) show a potential heart enlargement, especially in the left atrium, detectable by radiography. Due to digital radiography, different radiographic measurements estimate cardiac size quite uncomplicatedly. The Vertebral Heart Size (VHS), Radiographic Left Atrial Dimension (RLAD), Left Atrial Width (LAWidth), and the Vertebral Left Atrial Size (VLAS) used anatomical landmarks for measuring cardiac size in relation to the vertebral column. This study aimed to compare VHS, RLAD, LAWidth, and VLAS measured in conventional and inverted radiographs by veterinarians with different levels of experience in healthy dogs and dogs with MMVD. The reliability and user-friendliness of these measurements were evaluated, and the staging was compared to the echocardiography staging. A total of 50 unaffected dogs and 150 dogs with MMVD in stages B1, B2, and C were assessed. Three veterinarians with different levels of experience examined 200 conventional radiographs and their corresponding inverted radiographs blinded to the echocardiographic and clinical examination results. Analyses were performed to compare the measurements' grading and determine anatomical landmarks with measurement difficulties. Additionally, inter- and intraobserver agreement was assessed using intraclass correlation coefficient, and the agreement between radiographic and echocardiographic staging was compared using the kappa coefficient. The VHS, LAWidth, and VLAS were easier to define than the RLAD. The interobserver agreement was almost perfect for VHS (0.962) and good for the other radiographic measurements (RLAD: 0.778, LAWidth: 0.772, VLAS: 0.858). The VHS assigned the most dogs to the correct stage. However, VHS, RLAD, LAWidth, and VLAS presented an almost perfect intraobserver agreement. The dorsal left atrial margin of the RLAD was the most difficult measurement point to identify. The VHS is the most reproducible radiographic method for measuring the canine heart size and shows the highest agreement with echocardiography. An observer-related influence could be detected for RLAD, LAWidth, and VLAS.

Case report: Lympho-histiocytic meningoencephalitis with central nervous system vasculitis of unknown origin in three dogs.

Meningoencephalitis of unknown origin (MUO) is an umbrella term for a variety of subtypes of meningoencephalitis of dogs and cats with no identifiable infectious agent. In dogs, granulomatous meningoencephalitis (GME), necrotizing meningoencephalitis (NME), and necrotizing leukoencephalitis (NLE) are the most commonly reported subtypes. However, sporadically there are reports about other subtypes such as greyhound encephalitis or eosinophilic meningoencephalitis. The following case series presents three dogs with peracute to acute progressive signs of encephalopathy. The magnetic resonance imaging (MRI) of two dogs (post mortem n = 1/2) showed severe, diffuse swelling of the cortical gray matter with increased signal intensity in T2weighted (w) and fluid-attenuated inversion recovery (FLAIR) and decreased signal intensity in T1w. Additionally, focal to multifocal areas with signal void in both dogs and caudal transforaminal herniation of the cerebellum in one dog was observed. Post mortem histopathological examination revealed lympho-histiocytic encephalitis and central nervous system (CNS) vasculitis in all dogs. No infectious agents were detectable by histopathology (hematoxylin and eosin stain), periodic acid-Schiff reaction (PAS), Ziehl-Neelsen stain and immunohistochemistry for Canine adenovirus-1, Parvovirus, Listeria monocytogenes, Parainfluenzavirus, Toxoplasma gondii, Herpes-suis virus, Pan-Morbillivirus, Tick born encephalitis virus, Severe acute respiratory syndrome coronavirus (SARS-CoV) 2. Furthermore, two dogs were tested negative for rabies virus. To the best of the authors' knowledge, this is the first report of a lympho-histiocytic encephalitis with CNS vasculitis with no identifiable infectious agent. It is suggested to consider this as an additional subtype of MUO with severe clinical signs.

Evaluation of new and old biomarkers in dogs with degenerative mitral valve disease.

BACKGROUND: Dogs with degenerative mitral valve disease are commonly presented to small animal clinicians. Diagnosis, clinical staging, and therapeutic design are based on a combination of clinical examination, radiography, and echocardiography. To support diagnosis and clinical monitoring, a multi-marker-based approach would be conceivable. The aim of this study was to investigate the suitability of Galectin-3 and interleukin-1 receptor-like 1 protein (ST2) in dogs with degenerative mitral valve disease in accordance with N-terminal-prohormone-B-type natriuretic peptide (NT-proBNP) and cardiac troponin I (cTnI). For this purpose, serum concentrations of Galectin-3 and ST2 of 64 dogs with different stages of mitral valve disease and 21 dogs without cardiac disease were analyzed at the first examination and six months later. Echocardiography, blood cell count and clinical chemistry were performed and established biomarkers NT-proBNP and cTnI were measured additionally. Differences in the biomarker concentrations between all groups at both timepoints and the change in biomarker concentrations from first to second evaluation was investigated. Furthermore, correlations of each biomarker, between biomarkers and echocardiographic measurements, were calculated. Finally, the receiver-operating characteristic curve and the area under the curve analysis were performed to differentiate between disease stages and controls. RESULTS: Serum concentrations of Galectin-3 and ST2 were not statistically different between canine patients in the respective stages of mitral valve disease or in comparison to dogs in the control group at any timepoint. A significant increase in ST2 concentrations from the baseline to the follow-up examination was observed in dogs classified as stage B1 and the control group. The concentrations of NT-proBNP and cTnI in stage C dogs were significantly increased in comparison to the other groups. CONCLUSIONS: In this study, no relation between Galectin-3 and ST2 levels to the presence or stage of mitral valve disease could be detected. Nevertheless, considering the increase in ST2 concentrations from the first to second measurement, its value on monitoring disease progress could be feasible. In agreement with previous studies, NT-proBNP and cTnI have once more proven their utility in assessing disease severity. The approach of examining new cardiac biomarkers in dogs is still worth pursuing.

Holoprosencephalia, hypoplasia of corpus callosum and cerebral heterotopia in a male belted Galloway heifer with adipsia.

BACKGROUND: Specialized neurons in the diencephalon detect blood hypernatremia in dehydrated animals. These neurons are connected with the pituitary gland, subsequently producing antidiuretic hormone to reabsorb water from urine in the kidneys, and to the forebrain to generate thirst and trigger drinking behavior. CASE PRESENTATION: This is the first case report describing clinical findings, magnetic resonance imaging (MRI) and necropsy results of a Belted Galloway heifer with severe clinical signs of dehydration and hypernatremia, but concurrent adipsia and isosthenuria. Due to insufficient recovery with symptomatic treatment, owners elected euthanasia. Postmortem MRI and necropsy revealed a complex forebrain malformation: mild abnormal gyrification of the forebrain cortex, lobar holoprosencephaly, and corpus callosum hypoplasia. The affected brain structures are well known to be involved in osmoregulation and generation of thirst in dogs, humans and rodents. CONCLUSIONS: Complex forebrain malformation can be involved in the pathogenesis of hypernatremia and adipsia in bovines.

The effect of treatment with pimobendan in dogs with preclinical mitral valve disease - a placebo-controlled double-blinded crossover study.

BACKGROUND: Pimobendan is a widely used medication for the treatment of dogs with congestive heart failure (CHF) and preclinical degenerative mitral valve disease (DMVD) with cardiomegaly. The benefit of a treatment in dogs with preclinical DMVD but without cardiomegaly has not yet been elucidated. Some positive effects concerning life quality and a decrease in cardiac biomarkers could be verified. This study aimed to further investigate these results using a placebo-controlled double-blinded crossover design. Out of a total of 15 dogs, eight were allocated to sequence-group AB, in which dogs received pimobendan (A) during the first treatment period and placebo (B) during the second period. Accordingly, sequence-group BA was treated first with placebo followed by pimobendan. Each treatment period lasted six months and included a baseline investigation and follow-ups after 90 and 180 days. The investigations included a questionnaire completed by the owners, echocardiographic examination, and measurements of NT-proBNP, cTnI and lactate before and after a standardised submaximal exercise test. RESULTS: NT-proBNP values decreased significantly during the treatment period with pimobendan, and the post-exercise increase was attenuated at day 180. No significant treatment effects could be verified for cTnI and lactate, neither pre- nor post-exercise. Left ventricular size decreased under treatment, whereas no significant changes in left atrial size were detected. The owners described their dogs under treatment with pimobendan as being more active at day 90 (11/15) and day 180 (12/15). Those animals treated with placebo were described as being more active at day 90 (2/15) and day 180 (5/15). CONCLUSIONS: Pimobendan had reducing effects on the concentrations of pre- and post-exercise cardiac biomarkers and the size of the left ventricle in dogs with DMVD ACVIM B1. Exercise testing in addition to an assessment of cardiac biomarkers might improve the decision when to initiate pimobendan treatment in dogs with DMVD.

Do All Roads Lead to Rome? The Potential of Different Approaches to Diagnose Aelurostrongylus abstrusus Infection in Cats.

An infection with the cat lungworm, Aelurostrongylus abstrusus, can be subclinical, but it can also cause severe respiratory clinical signs. Larvae excretion, antibody levels, clinical assessment findings of the respiratory system and diagnostic imaging findings were recorded and compared for six cats with experimental aelurostrongylosis. In five cats, patency started 33-47 days post infection (pi), but two cats excreted larvae only in long intervals and low numbers. Positive ELISA results were observed in four cats with patent aelurostrongylosis, starting between five days before and 85 days after onset of patency. One seropositive cat remained copromicroscopically negative. Mild respiratory signs were observed in all cats examined. A computed tomographic (CT) examination of the lungs displayed distinct alterations, even in absence of evident clinical signs or when larvae excretion was low or negative. The thoracic radiograph evaluation correlated with the CT results, but CT was more distinctive. After anthelmintic treatment in the 25th week post infection, pulmonary imaging findings improved back to normal within 6-24 weeks. This study shows that a multifaceted approach, including diagnostic imaging, can provide a clearer diagnosis and monitoring of disease progression. Furthermore, a CT examination provides an alternative to post mortem examination and worm counts in anthelmintic efficacy studies.

Effects of isoflurane, remifentanil and dexmedetomidine on selected EEG parameters derived from a Narcotrend Monitor before and after nociceptive stimulation at different MAC multiples in cats.

BACKGROUND: The aim of this prospective and complete cross-over study was to evaluate the effects of isoflurane, remifentanil and dexmedetomidine on EEG parameters derived from the Narcotrend® Monitor before and after nociceptive stimulation at different isoflurane MAC (minimal alveolar concentration) multiples. Seven adult European Domestic Short Hair cats were used. Each cat went through 3 experimental treatments. Group I received isoflurane, group IR received isoflurane and a constant rate infusion (CRI) of remifentanil (18 µg/kg/h IV), and group ID received isoflurane and a CRI of dexmedetomidine (3 µg/kg/h IV). The isoflurane MAC in each group was determined via supramaximal electrical stimulation. The EEG parameters were derived by a Narcotrend Monitor at specific time points before and after nociceptive stimulation at 0.75, 1.0 and 1.5 MAC. The depth of anaesthesia was also assessed by a clinical score. RESULTS: The mean MAC sparing effects in group IR and group ID were 9.8 and 55.2%, respectively. The best correlation of EEG and MAC multiples was found for the Narcotrend Index (NI) in group I (r = - 0.67). The NI was also able to differentiate between 0.75 MAC and 1.5 MAC in group IR. Spectral edge frequency had a lower correlation with MAC multiples in group I (r = - 0.62) but was able to differentiate between 0.75 MAC and 1.5 MAC in groups I and IR, and between 1.0 MAC and 1.5 MAC in group IR. Narcotrend Index, SEF 95 and MF increased significantly after nociceptive stimulation at 1.0 MAC in group I, and SEF 95 increased significantly at 0.75 MAC in group ID. The clinical score correlated closer than any of the EEG parameters with MAC in all groups, with highest correlation values in group I (r = - 0.89). Noxious stimulation led to a significant increase of the clinical score at 0.75 MAC and 1.0 MAC in group I. CONCLUSIONS: The EEG parameters derived from the Narcotrend Monitor show correlation to isoflurane MAC multiples in cats, but the anaesthetic protocol and especially the addition of dexmedetomidine have great influence on the reliability. The Narcotrend Monitor can be used as an additional tool to assess anesthetic depth in cats.

Effect of pimobendan on physical fitness, lactate and echocardiographic parameters in dogs with preclinical mitral valve disease without cardiomegaly.

Pimobendan has gained enormous importance in the treatment of mitral valve disease in dogs. The current consensus statement of the American College of Veterinary Internal Medicine (ACVIM) recommends a treatment for dogs with symptomatic disease and dogs with asymptomatic disease with radiographic and echocardiographic signs of cardiomegaly. To investigate whether these dogs also benefit from a therapy with pimobendan, 21 dogs with mitral valve disease ACVIM B1 underwent a standardized submaximal exercise test on a treadmill. In this double-blinded and randomized study, the animals were divided into two groups, one receiving pimobendan and the other a placebo. At the first visit and at every follow-up appointment (at days 90 and 180), heart rate during the complete exercise test and lactate before and after running were measured. In addition to this, a questionnaire was completed by the dogs' owners and all dogs were given an echocardiographic examination to detect any changes and to observe if the disease had progressed. Due to the diagnosis of leishmaniosis, one dog in the pimobendan group was retrospectively removed from the study so that 20 dogs were included for statistical analysis. No differences were observed at any time between the pimobendan-group and the placebo-group regarding heart rate. At day 180, the increase in lactate after exercise was significantly lower than in the placebo-group. The increase in the pimobendan-group at day 180 was lower than at day 90. Most of the dog owners from the pimobendan-group declared that their dogs were more active at day 90 (6/10) and at day 180 (8/10), while most dog owners from the placebo-group observed no changes regarding activity at day 90 (8/10) and day 180 (6/10). It can be concluded that the results of this study indicate that some dogs with mitral valve disease ACVIM B1 might benefit from a therapy with pimobendan.

Experimental study on the effects of isoflurane with and without remifentanil or dexmedetomidine on heart rate variability before and after nociceptive stimulation at different MAC multiples in cats.

BACKGROUND: Heart rate variability (HRV) provides information about autonomic nervous system (ANS) activity and is therefore a possible tool with which to assess anaesthetic depth. The aim of the present study was to evaluate the effects of isoflurane, remifentanil and dexmedetomidine on HRV before and after nociceptive stimulation at different anaesthetic depths. Seven healthy domestic short-hair cats were used, and each cat was anaesthetized three times - group I with isoflurane alone, group IR with isoflurane and a constant rate infusion (CRI) of remifentanil (18 µg/kg/h), and group ID with isoflurane and a CRI of dexmedetomidine (3 µg/kg/h). Minimum alveolar concentration (MAC) values were determined via electrical supramaximal nociceptive stimulation for each treatment group. Nociceptive stimulation was repeated at 3 different MAC multiples (0.75, 1.0 and 1.5 MAC), and electrocardiographic recordings were performed for 3 min before and after stimulation. Only the 1 min epochs were used for further statistical analysis. Electrocardiographic data were exported for offline HRV analysis. RESULTS: The mean isoflurane MAC ± standard deviation (SD) was 1.83 ± 0.22 vol% in group I, 1.65 ± 0.13 vol% in group IR and 0.82 ± 0.20 vol% in group ID. Nociception was indicated by several HRV parameters, however, with high variability between treatments. The best correlation with MAC was found for the SD of heart rate (STD HR) in group I (rs = - 0.76, p = 0.0001, r2 = 0.46). STD HR was also able to distinguish 0.75 MAC from 1.5 MAC and 1.0 MAC from 1.5 MAC in group I, as well as 0.75 MAC from 1.5 MAC in group ID. CONCLUSIONS: The choice of anaesthetic protocol influences the HRV parameters in cats. Frequency domain parameters respond to nociception at lower MAC levels. The STD HR has the potential to provide additional information for the assessment of anaesthetic depth in isoflurane-anaesthetized cats. The utility of HRV analysis for the assessment of anaesthetic depth in cats is still questionable.

Effect of Pimobendan on NT-proBNP and c troponin I before and after a submaximal exercise test in dogs with preclinical mitral valve disease without cardiomegaly - a randomised, double-blinded trial.

BACKGROUND: Exercise testing in conjunction with measurement of cardiac biomarkers NT-proBNP and cTnI is a useful tool for monitoring the effect of treatment on cardiac patients. Administering Pimobendan in dogs with degenerative mitral valve disease (DMVD) and cardiomegaly results in delaying the onset of clinical symptoms and prolonging life. Its effect in dogs with DMVD without cardiomegaly has not been well examined. The aim of the current study was to investigate the effect of administering Pimobendan in dogs with DMVD without cardiomegaly using exercise testing in conjunction with measuring cardiac biomarkers in addition to echocardiography. Twenty-one dogs with asymptomatic DMVD without echocardiographic signs of cardiomegaly participated in a randomised, double-blinded trial. Dogs were divided into a Pimobendan-group (n = 11) and a placebo-group (n = 10) in a double-blinded study design and underwent a standardised submaximal exercise test (SSET). One dog in the Pimobendan-group was retrospectively removed from the study after being diagnosed with Leishmaniosis. Cardiac biomarkers NT-proBNP and cTnI were measured before and after exercise. Follow-up appointments were performed at days 90 and 180. RESULTS: Dogs in the Pimobendan-group had significantly lower post-exercise NT-proBNP-levels after being administered Pimobendan than at the beginning of the study. They also had lower pre- and post-exercise-NT-proBNP-levels than those dogs in the placebo-group. There was neither a significant difference regarding the measured cTnI levels nor an increase in cTnI between the groups at any time. CONCLUSIONS: Pimobendan lowers NT-proBNP in dogs with presymptomatic mitral valve disease without cardiomegaly before and after submaximal exercise. This indicates a reduction in cardiac wall stress. If dogs with asymptomatic DMVD without cardiomegaly benefit from treatment with Pimobendan (for example, through a longer survival time) warrants further investigation.