Incidence rates of the most common canine tumors based on data from the Swiss Canine Cancer Registry (2008 to 2020).

Monitoring neoplasms in standardized registries facilitates epidemiologic studies of risk factors for tumor development and predisposition. In an observational study, we determined incidence rates (IR) and malignant tumor incidence rate ratios (IRR) by age, sex, and breed in Swiss dogs using demographic data from the official Swiss dog registration database Amicus. The dataset analyzed included 54'986 tumors diagnosed by histology and cytology in four Swiss veterinary pathology laboratories between 2008 and 2020. Diagnoses were coded according to the Vet-ICD-O-canine-1 system. Most tumors occurred in the skin (n = 19'045; 34.64%), soft tissues (n = 11'092; 20.17%), and mammary glands (n = 7'974; 14.50%). The IRs for all and for malignant tumors were 775/100'000 dog-years at risk (95%CI 764-777) and 338/100'000 dog-years at risk (95%CI 333-342), respectively. Females (850; 95%CI 834-853) had a higher overall tumor IR than males (679; 95%CI 666-684). The highest tumor IR was found at 11 years of age (1'857; 95%CI 1'780-1'867). Potential novel breed-specific predispositions were uncovered, with high IRs for several benign and malignant tumors in Polski Owczarek Nizinnys (overall IR: 3'303; 95%CI 2'502-3'864) and high IRs for malignant tumors in Russian Black Terriers (melanomas: 345; 95%CI 138-708), Field Spaniels (adenocarcinomas: 376; CI95% 138-817), Dogo Argentinos (mast cell tumors: 844; CI95% 591-1'169), King Charles Spaniels and Manchester Terriers (lymphomas: 319; CI95% 137-627 and 302; CI95% 98-704, respectively), Landseers (osteosarcomas: 74; CI95% 15-216), Bouvier des Flandres (hemangiosarcomas: 127; CI95% 26-371), and Bearded Collies and Cane Corso Italianos (gliomas: 91; CI95% 45-162 and 34; CI95% 7-99, respectively). Nordic hunting dogs had the highest (8.08; CI95% 3.55-16.7) and Chihuahueno the lowest cancer IRRs (0.42; 95%CI 0.31-0.57) compared to mixed breeds. In conclusion, the calculated IRs and IRRs revealed previously unknown predisposing factors, including novel breed-specific susceptibilities. The results may have implications for cancer screening, diagnostic work-up, breeding management and oncologic and translational research.

Fatal tick-borne encephalitis virus infection in Dalmatian puppy-dogs after putative vector independent transmission.

In a retrospective metatranscriptomics study, we identified tick-borne encephalitis virus (TBEV) to be the causative agent for a fatal non-suppurative meningoencephalitis in a three-week-old Dalmatian puppy in Switzerland. Further investigations showed that the two other littermates with similar signs and pathological lesions were also positive for TBEV. By using an unbiased approach of combining high-throughput sequencing (HTS) and bioinformatics we were able to solve the etiology and discover an unusual case of TBEV in three young puppies. Based on our findings, we suggest that a vector-independent transmission of TBEV occurred and that most likely an intrauterine infection led to the severe and fulminant disease of the entire litter. We were able to demonstrate the presence of TBEV RNA by in situ hybridization (ISH) in the brain of all three puppies. Furthermore, we were able to detect TBEV by RT-qPCR in total RNA extracted from formalin-fixed and paraffin embedded (FFPE) blocks containing multiple peripheral organs. Overall, our findings shed light on alternative vector-independent transmission routes of TBEV infections in dogs and encourage veterinary practitioners to consider TBEV as an important differential diagnosis in neurological cases in dogs.

LISTERIA MONOCYTOGENES INFECTION IN FREE-RANGING RED FOXES (VULPES VULPES) AND EURASIAN LYNX (LYNX LYNX) IN SWITZERLAND.

Listeria monocytogenes is an ubiquitous environmental saprophytic bacterium causing listeriosis in domestic animals, humans, and occasionally wildlife. In animals, this foodborne zoonotic disease mainly occurs in ruminants and it is rare in carnivores. Seven red foxes (Vulpes vulpes) and one Eurasian lynx (Lynx lynx) were diagnosed with listeriosis between 2010 and 2021 at the Institute for Fish and Wildlife Health, Bern, Switzerland. Necropsy and histopathology revealed meningitis (six of seven red foxes), hepatitis (six of seven red foxes), pneumonia (five of seven red foxes), splenitis (two of seven red foxes) and splenomegaly (the Eurasian lynx, two of seven red foxes). Listeria monocytogenes was isolated from either lung, spleen, liver, or kidney of all animals. Serotyping detected L. monocytogenes serotype 1/2a in five red foxes and the Eurasian lynx and serotype 4b in two red foxes. Six red foxes were positive for canine distemper virus (CDV) by polymerase chain reaction, whereas the Eurasian lynx and one red fox were negative. One red fox that was positive for CDV and listeriosis was also diagnosed with salmonellosis. The identified L. monocytogenes serotypes are among the three most frequently isolated serotypes (1/2a, 1/2b, and 4b) from food or the food production environment and those that cause most listeriosis cases in humans and animals. Coinfection with CDV in six red foxes questions the role of CDV as potential predisposing factor for septicemic listeriosis. The detection of listeriosis in the regionally endangered Eurasian lynx and in carnivores highly abundant in urban settings, such as red foxes, reinforces the importance of wildlife health surveillance in a One Health context and adds the Eurasian lynx to the list of carnivores susceptible to the disease. Further investigations are required to assess the prevalence and epidemiology of L. monocytogenes in free-ranging carnivores and its interaction with CDV.

Canine glioblastoma-derived extracellular vesicles as precise carriers for glioblastoma imaging: Targeting across the blood-brain barrier.

The treatment of glioblastoma (GBM) faces significant challenges due to the difficulty of delivering drugs through the blood-brain barrier (BBB). Extracellular vesicles (EVs) have emerged as potential carriers for targeted drug delivery to brain tumors. However, their use and distribution in the presence of an intact BBB and their ability to target GBM tissue are still under investigation. This study explored the use of EVs for GBM targeting across the BBB. Canine plasma EVs from healthy dogs and dogs with glioma were isolated, characterized, and loaded with diagnostic agents. Biodistribution studies were conducted in healthy murine models and a novel intranasal model that preserved BBB integrity while initiating early-stage GBM growth. This model assessed EVs' potential for delivering the contrast agent gadoteric acid to intracranial tumors. Imaging techniques, such as bioluminescence and MRI, confirmed EVs' targeting and delivery capabilities thus revealing a selective accumulation of canine glioma-derived EVs in brain tissue under physiological conditions. In the model of brain tumor, MRI experiments demonstrated the ability of EVs to accumulate gadoteric acid within GBM to enhance contrast of the tumoral mass, even when BBB integrity is maintained. This study underscores the potential of EVs derived from glioma for the targeted delivery of drugs to glioblastoma. EVs from dogs with glioma showed capacity to traverse the BBB and selectively accumulate within the brain tumor. Overall, this research represents a foundation for the application of autologous EVs to precision glioblastoma treatment, addressing the challenge of BBB penetration and targeting specificity in brain cancer therapy.

PCYT2 deficiency in Saarlooswolfdogs with progressive retinal, central, and peripheral neurodegeneration.

We investigated a syndromic disease comprising blindness and neurodegeneration in 11 Saarlooswolfdogs. Clinical signs involved early adult onset retinal degeneration and adult-onset neurological deficits including gait abnormalities, hind limb weakness, tremors, ataxia, cognitive decline and behavioral changes such as aggression towards the owner. Histopathology in one affected dog demonstrated cataract, retinal degeneration, central and peripheral axonal degeneration, and severe astroglial hypertrophy and hyperplasia in the central nervous system. Pedigrees indicated autosomal recessive inheritance. We mapped the suspected genetic defect to a 15 Mb critical interval by combined linkage and autozygosity analysis. Whole genome sequencing revealed a private homozygous missense variant, PCYT2:c.4A>G, predicted to change the second amino acid of the encoded ethanolamine-phosphate cytidylyltransferase 2, XP_038402224.1:(p.Ile2Val). Genotyping of additional Saarlooswolfdogs confirmed the homozygous genotype in all eleven affected dogs and demonstrated an allele frequency of 9.9% in the population. This experiment also identified three additional homozygous mutant young dogs without overt clinical signs. Subsequent examination of one of these dogs revealed early-stage progressive retinal atrophy (PRA) and expansion of subarachnoid CSF spaces in MRI. Dogs homozygous for the pathogenic variant showed ether lipid accumulation, confirming a functional PCYT2 deficiency. The clinical and metabolic phenotype in affected dogs shows some parallels with human patients, in whom PCYT2 variants lead to a rare form of spastic paraplegia or axonal motor and sensory polyneuropathy. Our results demonstrate that PCYT2:c.4A>G in dogs cause PCYT2 deficiency. This canine model with histopathologically documented retinal, central, and peripheral neurodegeneration further deepens the knowledge of PCYT2 deficiency.

Feline morbillivirus infection associated with fatal encephalitis in a Bengal cat.

Feline morbillivirus (FeMV) is a recently discovered morbillivirus of the family Paramyxoviridae, which include several highly contagious viruses with zoonotic potential. In this case report we describe the detection of FeMV in archived brain tissue of a 2-month-old Bengal cat with nonsuppurative encephalitis from the year 2011 in Switzerland by high-throughput sequencing (HTS). Our metagenomics approach was able to obtain a full-length sequence covering the entire FeMV genome. Phylogenetic analysis showed that our FeMV strain clustered within FeMV genotype 1. We were able to detect FeMV RNA by in situ hybridization (ISH) in brain sections with inflammatory lesions and demonstrated its potential neurotropism and association with encephalitis. Our results provide further insight into this recently discovered morbillivirus and encourage further investigations into the pathogenesis and epidemiology of associated diseases in cats and potentially other species.

DYRK1B haploinsufficiency in a Holstein cattle with epilepsy.

In this study, epilepsy with focal seizures progressing to generalized seizures was diagnosed in a 6-month-old Holstein heifer. The seizures were characterized by a brief pre-ictal phase with depression and vocalization. During the ictal phase eyelid spasms, tongue contractions, nodding and abundant salivation were observed, rapidly followed by a convulsive phase with bilateral tonic, clonic or tonic-clonic activity and loss of consciousness. Finally, during the postictal phase the heifer was obtunded and disorientated, unable to perceive obstacles and hypermetric, and pressed its head against objects. In the inter-seizure phase, the heifer was clinically normal. Neuropathology revealed axonal degeneration in the brainstem and diffuse astrocytic hypertrophic gliosis. Whole genome sequencing of the affected heifer identified a private heterozygous splice-site variant in DYRK1B (NM_001081515.1: c.-101-1G>A), most likely resulting in haploinsufficiency owing to loss-of-function. This represents a report of a DYRK1B-associated disease in cattle and adds DYRK1B to the candidate genes for epilepsy.

Standardization of canine meningioma grading: Validation of new guidelines for reproducible histopathologic criteria.

Canine meningiomas are currently graded using the human grading system. Recently published guidelines have adapted the human grading system for use in dogs. The goal of this study was to validate the new guidelines for canine meningiomas. To evaluate the inter-observer agreement, 5 veterinary surgical pathologists graded 158 canine meningiomas following the human grading system alone or with the new guidelines. The inter-observer agreement for histologic grade and each of the grading criteria (mitotic grade, invasion, spontaneous necrosis, macronucleoli, small cells, hypercellularity, pattern loss and anaplasia) was evaluated using the Fleiss kappa index. The diagnostic accuracy (sensitivity and specificity) was assessed by comparing the diagnoses obtained with the 2 grading systems with a consensus grade (considered the reference classification). The consensus histologic grade was obtained by agreement between 4 experienced veterinary neuropathologists following the guidelines. Compared with the human grading alone, the canine-specific guidelines increased the inter-observer agreement for: histologic grade (κ = 0.52); invasion (κ = 0.67); necrosis (κ = 0.62); small cells (κ = 0.36); pattern loss (κ = 0.49) and anaplasia (κ = 0.55). Mitotic grade agreement remained substantial (κ = 0.63). The guidelines improved the sensitivity in identifying grade 1 (95.6%) and the specificity in identifying grade 2 (96.2%) meningiomas. In conclusion, the new grading guidelines for canine meningiomas are associated with an overall improvement in the inter-observer agreement and higher diagnostic accuracy in diagnosing grade 1 and grade 2 meningiomas.

Machine learning predicts histologic type and grade of canine gliomas based on MRI texture analysis.

Conventional MRI features of canine gliomas subtypes and grades significantly overlap. Texture analysis (TA) quantifies image texture based on spatial arrangement of pixel intensities. Machine learning (ML) models based on MRI-TA demonstrate high accuracy in predicting brain tumor types and grades in human medicine. The aim of this retrospective, diagnostic accuracy study was to investigate the accuracy of ML-based MRI-TA in predicting canine gliomas histologic types and grades. Dogs with histopathological diagnosis of intracranial glioma and available brain MRI were included. Tumors were manually segmented across their entire volume in enhancing part, non-enhancing part, and peri-tumoral vasogenic edema in T2-weighted (T2w), T1-weighted (T1w), FLAIR, and T1w postcontrast sequences. Texture features were extracted and fed into three ML classifiers. Classifiers' performance was assessed using a leave-one-out cross-validation approach. Multiclass and binary models were built to predict histologic types (oligodendroglioma vs. astrocytoma vs. oligoastrocytoma) and grades (high vs. low), respectively. Thirty-eight dogs with a total of 40 masses were included. Machine learning classifiers had an average accuracy of 77% for discriminating tumor types and of 75.6% for predicting high-grade gliomas. The support vector machine classifier had an accuracy of up to 94% for predicting tumor types and up to 87% for predicting high-grade gliomas. The most discriminative texture features of tumor types and grades appeared related to the peri-tumoral edema in T1w images and to the non-enhancing part of the tumor in T2w images, respectively. In conclusion, ML-based MRI-TA has the potential to discriminate intracranial canine gliomas types and grades.

Epithelial membrane antigen-reactive feline chordoid meningioma in a European wildcat (Felis silvestris).

Meningioma is the most frequent intracranial neoplasm in cats. Here we describe the first case of chordoid meningioma (CM), a rare grade II meningioma subtype, in a 5.5-year-old European wildcat (Felis silvestris) from a Swiss zoo. The wildcat was found dead after a clinical history of neurological signs and clinical suspicion of a carcinoma in the right external ear canal with concurrent chronic otitis. Post-mortem examination revealed a large intracranial, extra-axial and intradural neoplasm that invaded into the right ear canal and had histological features compatible with CM, which has been only reported in humans and dogs. Neoplastic cells expressed vimentin but were negative for glial fibrillary acidic protein, S100 and pancytokeratin. Immunohistochemistry revealed epithelial membrane antigen (EMA) expression in neoplastic cells. To the best of our knowledge, we provide the first evidence of EMA expression in feline meningioma.

Immunization with a Multivalent Listeria monocytogenes Vaccine Leads to a Strong Reduction in Vertical Transmission and Cerebral Parasite Burden in Pregnant and Non-Pregnant Mice Infected with Neospora caninum.

Neospora caninum is an apicomplexan parasite that causes abortion and stillbirth in cattle. We employed the pregnant neosporosis mouse model to investigate the efficacy of a modified version of the attenuated Listeria monocytogenes vaccine vector Lm3Dx_NcSAG1, which expresses the major N. caninum surface antigen SAG1. Multivalent vaccines were generated by the insertion of gra7 and/or rop2 genes into Lm3Dx_NcSAG1, resulting in the double mutants, Lm3Dx_NcSAG1_NcGRA7 and Lm3Dx_NcSAG1_NcROP2, and the triple mutant, Lm3Dx_NcSAG1_NcGRA7_NcROP2. Six experimental groups of female BALB/c mice were inoculated intramuscularly three times at two-week intervals with 1 × 107 CFU of the respective vaccine strains. Seven days post-mating, mice were challenged by the subcutaneous injection of 1 × 105N. caninum NcSpain-7 tachyzoites. Non-pregnant mice, dams and their offspring were observed daily until day 25 post-partum. Immunization with Lm3Dx_NcSAG1 and Lm3Dx_NcSAG1_NcGRA7_NcROP2 resulted in 70% postnatal pup survival, whereas only 50% and 58% of pups survived in the double mutant-vaccinated groups. Almost all pups had died at the end of the experiment in the infection control. The triple mutant was the most promising vaccine candidate, providing the highest rate of protection against vertical transmission (65%) and CNS infection. Overall, integrating multiple antigens into Lm3Dx_SAG1 resulted in lower vertical transmission and enhanced protection against cerebral infection in dams and in non-pregnant mice.

Osteopontin and Ki-67 expression in World Health Organization graded canine meningioma.

Osteopontin (OPN) is a matrix protein involved in tumour initiation and progression. In human meningioma, OPN has been correlated with World Health Organization (WHO) grade, brain invasion and recurrence. The aim of this study was to investigate OPN as a possible malignancy marker in canine meningioma by correlating its expression to WHO grade and proliferative activity as measured by the Ki-67 labelling index (LI). Thirty-five formalin-fixed, paraffin-embedded canine meningioma samples were classified according to the current human WHO classification. Evaluation of OPN expression was performed by immunohistochemical (IHC) labelling and calculation of the OPN intensity score (IS), OPN IHC score and Allred score. The scores were compared with WHO grades, Ki-67 LI, location and invasiveness. Nineteen meningiomas were graded as WHO grade I (54.3%), nine as grade II (25.7%) and seven as grade III (20.0%). Twenty-six tumours were located intracranially, four were retrobulbar and five were spinal meningiomas. In all specimens OPN expression was detected in moderate to high degrees. Neither the OPN scores nor the Ki-67 LIs were correlated with WHO grades. However, the OPN IS and OPN IHC score were significantly higher in WHO grade I samples compared with grade II samples (P <0.05). The OPN IS and OPN IHC score were significantly lower in meningioma samples that invaded surrounding tissues (P = 0.01 and 0.019, respectively). The results indicate a generally high expression of OPN in canine meningioma independent of WHO grade. Further research into the role of OPN as a possible therapeutic target or predictor of recurrence is warranted.

MRI ischemic and hemorrhagic lesions in arterial and venous territories characterize central nervous system intravascular lymphoma in dogs.

Intravascular lymphoma (IVL) is characterized by the proliferation of large malignant lymphocytes within the lumen of blood vessels. This retrospective, multi-center, case series study aimed to describe the MRI features of confirmed central nervous system IVL in dogs and compare them with histopathological findings. Medical record databases from seven veterinary centers were searched for cases of histologically confirmed IVL. Dogs were included if an MRI was performed. The MRI studies and histopathology samples were reviewed to compare the MRI changes with the histopathological findings. Twelve dogs met the inclusion criteria (12 brains and three spinal cords). Imaging of the brains revealed multifocal T2-weighted/FLAIR hyperintense and T1-weighted iso-hypointense lesions, with variable contrast enhancement; areas of abnormal diffusion both in arterial and venous territories in diffusion-weighted imaging; and meningeal enhancement. On gradient echo images (GRE), the changes comprised tubular susceptibility artifacts, consistent with the "susceptibility vessel sign", and additional variably sized/shaped intraparenchymal susceptibility artifacts. Spinal cord lesions presented as fusiform T2-weighted hyperintensities with scattered susceptibility artifacts on GRE and variable parenchymal and meningeal contrast enhancement. On histopathology, subarachnoid hemorrhages and neuroparenchymal areas of edema and necrosis, with or without hemorrhage, indicating ischemic and hemorrhagic infarctions, were found. These lesions were concurrent with severely dilated meningeal and parenchymal arteries and veins plugged by neoplastic lymphocytes and fibrin. Due to the unique angiocentric distribution of IVL, ischemic and hemorrhagic infarcts of variable chronicity affecting both the arterial and venous territories associated with thrombi formation can be detected on MRI.

Bovine neutrophil chemotaxis to Listeria monocytogenes in neurolisteriosis depends on microglia-released rather than bacterial factors.

BACKGROUND: Listeria monocytogenes (Lm) is a bacterial pathogen of major concern for humans and ruminants due to its neuroinvasive potential and its ability to cause deadly encephalitis (neurolisteriosis). On one hand, polymorphonuclear neutrophils (PMN) are key players in the defense against Lm, but on the other hand intracerebral infiltration with PMN is associated with significant neural tissue damage. Lm-PMN interactions in neurolisteriosis are poorly investigated, and factors inducing PMN chemotaxis to infectious foci containing Lm in the central nervous system (CNS) remain unidentified. METHODS: In this study, we assessed bovine PMN chemotaxis towards Lm and supernatants of infected endogenous brain cell populations in ex vivo chemotaxis assays, to identify chemotactic stimuli for PMN chemotaxis towards Lm in the brain. In addition, microglial secretion of IL-8 was assessed both ex vivo and in situ. RESULTS: Our data show that neither Lm cell wall components nor intact bacteria elicit chemotaxis of bovine PMN ex vivo. Moreover, astrocytes and neural cells fail to induce bovine PMN chemotaxis upon infection. In contrast, supernatant from Lm infected microglia readily induced chemotaxis of bovine PMN. Microglial expression and secretion of IL-8 was identified during early Lm infection in vitro and in situ, although IL-8 blocking with a specific antibody could not abrogate PMN chemotaxis towards Lm infected microglial supernatant. CONCLUSIONS: These data provide evidence that host-derived rather than bacterial factors trigger PMN chemotaxis to bacterial foci in the CNS, that microglia have a primary role as initiators of bovine PMN chemotaxis into the brain during neurolisteriosis and that blockade of these factors could be a therapeutic target to limit intrathecal PMN chemotaxis and PMN associated damage in neurolisteriosis.

Grading of oligodendroglioma in dogs based on magnetic resonance imaging.

BACKGROUND: Oligodendroglioma (OG) accounts for 22% of primary brain tumors in dogs. Oligodendroglioma in dogs is graded as low-grade (II) or high-grade (III), based on the presence of microvascular proliferation and necrosis. OBJECTIVE: To investigate if magnetic resonance imaging (MRI) features differ between OG II and III in dogs. ANIMALS: Thirty-two dogs with histological diagnosis of intracranial OG and MRI. METHODS: Retrospective descriptive study. Histology was reviewed to grade OG according to the revised classification. Brain MRI results were reviewed following criteria including contrast enhancement (CE) pattern, presence of cystic structures, gradient-recalled-echo (GRE) signal voids, and necrosis based on signal intensity, as well as diffusion-weighted imaging characteristics. The MRI features were compared between OG II and III using Fisher's exact tests and logistic regression models. RESULTS: Histology identified 8 dogs with OG II (25%) and 24 with OG III (75%). All OG III showed moderate-to-marked CE including 18/24 (75%) with a ring pattern. These features were not seen in OG II. Heterogeneity, cystic structures, GRE signal voids, and necrosis were associated with OG III. No difference in diffusion characteristics was detected between OG II and III. CONCLUSION AND CLINICAL IMPORTANCE: Moderate-to-marked CE and ring pattern were present in dogs with OG III but not in OG II. The presence of cystic structures, GRE signal voids, and necrosis was strongly associated with OG III. Although the importance of brain tumor grading in dogs with regard to prognosis and treatment options remains unknown, the results indicate that MRI reflects the histological features used for grading OG in dogs.

Concomitant necrotizing encephalitis and granulomatous meningoencephalitis in four toy breed dogs.

The term "meningoencephalitis of unknown origin" (MUO) describes a group of different encephalitides in dogs in which no infectious agent can be identified and a multifactorial etiology is suspected. Among others, genetic factors and unknown triggers seem to be involved. Included are necrotizing leukoencephalitis (NLE), necrotizing meningoencephalitis (NME), and granulomatous meningoencephalitis (GME). In this case series, we describe the histopathological findings of four toy breed dogs with focal or multifocal necrotizing encephalitis and mainly lymphocytic perivascular infiltrates on histopathological examination. At the same time, however, in all dogs, focal or multifocal high-grade angiocentric granulomatous inflammatory lesions were evident with focal histiocytic perivascular infiltrates in the brain. The former changes are typical for NLE and NME. In contrast, the latter changes are indicative of GME. This case series shows that the boundaries between the necrotizing and granulomatous variants of MUO might be smooth and suggests that NLE, NME, and GME are not as distinct as previously described. This finding could be a crucial piece of the puzzle in the study of the pathogenesis of MUO as individual susceptibility and specific triggers could be responsible for the manifestation of the different MUO subtypes.

Vaccine-Linked Chemotherapy Approach: Additive Effects of Combining the Listeria monocytogenes-Based Vaccine Lm3Dx_NcSAG1 With the Bumped Kinase Inhibitor BKI-1748 Against Neospora caninum Infection in Mice.

The apicomplexan parasite Neospora (N.) caninum causes neosporosis in numerous host species. There is no marketed vaccine and no licensed drug for the prevention and/or treatment of neosporosis. Vaccine development against this parasite has encountered significant obstacles, probably due to pregnancy-induced immunomodulation hampering efficacy, which has stimulated the search for potential drug therapies that could be applied to limit the effects of neosporosis in dams as well as in offspring. We here investigated, in a pregnant neosporosis mouse model, the safety and efficacy of a combined vaccination-drug treatment approach. Mice were vaccinated intramuscularly with 1 × 107 CFU of our recently generated Listeria (L.) monocytogenes vaccine vector expressing the major N. caninum tachyzoite surface antigen NcSAG1 (Lm3Dx_SAG1). Following mating and experimental subcutaneous infection with 1 × 105 N. caninum (NcSpain-7) tachyzoites on day 7 of pregnancy, drug treatments were initiated using the bumped kinase inhibitor BKI-1748 at 20 mg/kg/day for 5 days. In parallel, other experimental groups were either just vaccinated or only treated. Dams and offspring were followed-up until day 25 post-partum, after which all mice were euthanized. None of the treatments induced adverse effects and neither of the treatments affected fertility or litter sizes. Cerebral infection in dams as assessed by real-time PCR was significantly reduced in the vaccinated and BKI-1748 treated groups, but was not reduced significantly in the group receiving the combination. However, in non-pregnant mice, all three treatment groups exhibited significantly reduced parasite burdens. Both, vaccination as well BKI-1748 as single treatment increased pup survival to 44 and 48%, respectively, while the combination treatment led to survival of 86% of all pups. Vertical transmission in the combination group was 23% compared to 46 and 50% in the groups receiving only BKI-treatment or the vaccine, respectively. In the dams, IgG titers were significantly reduced in all treatment groups compared to the untreated control, while in non-pregnant mice, IgG titers were reduced only in the group receiving the vaccine. Overall, vaccine-linked chemotherapy was more efficacious than vaccination or drug treatment alone and should be considered for further evaluation in a more relevant experimental model.

Can MRI differentiate between ring-enhancing gliomas and intra-axial abscesses?

Gliomas of the brain may appear as expansile ring-enhancing masses in MRI studies, mimicking the appearance of intra-axial abscesses. The aims of this study were to compare the MRI features of ring-enhancing gliomas and intra-axial brain abscesses in dogs and cats and to identify the characteristics that might help differentiate them. For this multicenter, retrospective, and observational study, the inclusion criteria were as follows: (a) a definitive diagnosis of glioma or abscess based on cytological or histopathological examination following CSF collection or surgical biopsy/necropsy, respectively; (b) MRI study performed with a high- or low-field MRI scanner, including a same plane T1W pre- and postcontrast, a T2W and a T2 FLAIR sequence in at least one plane. If available, delayed T1W postcontrast, T2*W GE, DWI/ADC, and SWI sequences were also evaluated. Sixteen patients were diagnosed with ring-enhancing gliomas, and 15 were diagnosed with intra-axial abscesses. A homogenous signal on T1W (P = 0.049) and T2W (P = 0.042) sequences, a T2W (P = 0.005) or T2*W GE (P = 0.046) peripheral hypointense halo, and an even enhancing capsule (P = 0.002) were significantly associated with brain abscesses. A progressive central enhancement on delayed T1W postcontrast sequences was correlated with ring-enhancing gliomas (P = 0.009). The combination of the following features was suggestive of brain abscess: homogeneous T1W or T2W signal intensity, a T2W or T2*W GE peripheral hypointense halo and an evenly enhancing capsule. Central progression of enhancement on delayed T1W postcontrast sequences was suggestive of glioma.

Vet-ICD-O-Canine-1, a System for Coding Canine Neoplasms Based on the Human ICD-O-3.2.

Cancer registries are fundamental tools for collecting epidemiological cancer data and developing cancer prevention and control strategies. While cancer registration is common in the human medical field, many attempts to develop animal cancer registries have been launched over time, but most have been discontinued. A pivotal aspect of cancer registration is the availability of cancer coding systems, as provided by the International Classification of Diseases for Oncology (ICD-O). Within the Global Initiative for Veterinary Cancer Surveillance (GIVCS), established to foster and coordinate animal cancer registration worldwide, a group of veterinary pathologists and epidemiologists developed a comparative coding system for canine neoplasms. Vet-ICD-O-canine-1 is compatible with the human ICD-O-3.2 and is consistent with the currently recognized classification schemes for canine tumors. It comprises 335 topography codes and 534 morphology codes. The same code as in ICD-O-3.2 was used for the majority of canine tumors showing a high level of similarity to their human counterparts (n = 408). De novo codes (n = 152) were created for specific canine tumor entities (n = 126) and topographic sites (n = 26). The Vet-ICD-O-canine-1 coding system represents a user-friendly, easily accessible, and comprehensive resource for developing a canine cancer registration system that will enable studies within the One Health space.