Canine idiopathic generalized tremor syndrome, immune-mediated?

Idiopathic generalized tremor syndrome is a disorder characterized by an acute onset of full-body tremors, sometimes accompanied by vestibulo-cerebellar signs, that is responsive to treatment with corticosteroids. Although considered to have an overall good outcome, relapsing and persistent mild clinical signs have been described. So far, little is known about the etiopathology of this syndrome, but it is believed to have an immune-mediated origin. In human medicine, description of numerous autoantibodies involved in certain non-infectious neurologic disorders has revolutionized understanding of their pathophysiology, diagnosis and treatment. In this multicenter retrospective study, we aimed to describe the clinical signs, course, and outcome of dogs with idiopathic generalized tremor syndrome and correlate potential findings with the presence or absence of autoantibodies associated with autoimmune cerebellar syndromes in humans. Information regarding signalment, history, clinical signs, laboratory findings, diagnostic imaging and testing for regional infectious diseases was gathered and the remaining serum and CSF samples were then analyzed for neural antibodies against targets associated with autoimmune encephalitic diseases of humans. Thirty-three dogs were included, and screening for neural antibodies was performed in 30 of those dogs. The analysis showed an increased titer of mGluR1 antibodies in two dogs, GFAP and later in the course of disease mGluR1 antibodies in one dog and an increase in unspecific autoantibodies which could not be further classified in two dogs. Dogs with detectable neural autoantibodies always had cerebrospinal fluid abnormalities in the form of a pleocytosis, with or without increased protein concentration, and tended to present with hyperthermia, potentially indicating a more severe clinical form of idiopathic generalized tremor syndrome in these cases. In conclusion, idiopathic generalized tremor syndrome is proposed to be an immune-mediated disorder potentially mediated by neural autoantibodies in a subgroup of dogs.

Synovial fluid D-lactate - a pathogen-specific biomarker for septic arthritis: a prospective multicenter study.

OBJECTIVES: The performance of synovial fluid biomarker D-lactate to diagnose septic arthritis (SA) and differentiate it from crystal-induced arthritis (CA), other non-infectious rheumatic joint diseases (RD) and osteoarthrosis (OA) was evaluated. METHODS: Consecutive adult patients undergoing synovial fluid aspiration due to joint pain were prospectively included in different German and Swiss centers. Synovial fluid was collected for culture, leukocyte count and differentiation, detection of crystals, and D-lactate concentration. Youden's J statistic was used to determine optimal D-lactate cut-off value on the receiver operating characteristic (ROC) curve by maximizing sensitivity and specificity. RESULTS: In total 231 patients were included. Thirty-nine patients had SA and 192 aseptic arthritis (56 patients with OA, 68 with CA, and 68 with RD). The median concentration of synovial fluid D-lactate was significantly higher in patients with SA than in those with OA, CA, and RD (p<0.0001, p<0.0001 and p<0.0001, respectively). The optimal cut-off of synovial fluid D-lactate to diagnose SA was 0.033 mmol/L with a sensitivity of 92.3 % and specificity of 85.4 % independent of previous antimicrobial treatment. Sensitivity and specificity of synovial fluid leukocyte count at a cut-off of 20,000 cells/µL was 81.1 % and 80.8 %, respectively. CONCLUSIONS: Synovial fluid D-lactate showed a high performance for diagnosing SA which was superior to synovial fluid leukocyte count. Given its high sensitivity and specificity, it serves as both an effective screening tool for SA and a differentiator between SA and RD, especially CA.

Evaluating ChatGPT responses to frequently asked patient questions regarding periprosthetic joint infection after total hip and knee arthroplasty.

Background: Patients access relevant information concerning their orthopaedic surgery resources through multiple information channels before presenting for clinical treatment. Recently, artificial intelligence (AI)-powered chatbots have become another source of information for patients. The currently developed AI chat technology ChatGPT (OpenAI LP) is an application for such purposes and it has been rapidly gaining popularity, including for patient education. This study sought to evaluate whether ChatGPT can correctly answer frequently asked questions (FAQ) regarding periprosthetic joint infection (PJI). Methods: Twelve FAQs about PJI after hip and knee arthroplasty were identified from the websites of fifteen international clinical expert centres. ChatGPT was confronted with these questions and its responses were analysed for their accuracy using an evidence-based approach by a multidisciplinary team. Responses were categorised in four groups: (1) Excellent response that did not require additional improvement; (2) Satisfactory responses that required a small amount of improvement; (3) Satisfactory responses that required moderate improvement; and (4) Unsatisfactory responses that required a large amount of improvement. Results: From the analysis of the responses given by the chatbot, no reply received an 'unsatisfactory' rating; one did not require any correction; and the majority of the responses required low (7 out of 12) or moderate (4 out of 12) clarification. Although a few responses required minimal clarification, the chatbot responses were generally unbiased and evidence-based, even when asked controversial questions. Conclusions: The AI-chatbot ChatGPT was able to effectively answer the FAQs of patients seeking information around PJI diagnosis and treatment. The given information was also written in a manner that can be assumed to be understandable by patients. The chatbot could be a valuable clinical tool for patient education and understanding around PJI treatment in the future. Further studies should evaluate its use and acceptance by patients with PJI.

Behavioral comorbidities treatment by fecal microbiota transplantation in canine epilepsy: a pilot study of a novel therapeutic approach.

Introduction: Anxiety and cognitive dysfunction are frequent, difficult to treat and burdensome comorbidities in human and canine epilepsy. Fecal microbiota transplantation (FMT) has been shown to modulate behavior in rodent models by altering the gastrointestinal microbiota (GIM). This study aims to investigate the beneficial effects of FMT on behavioral comorbidities in a canine translational model of epilepsy. Methods: Nine dogs with drug-resistant epilepsy (DRE) and behavioral comorbidities were recruited. The fecal donor had epilepsy with unremarkable behavior, which exhibited a complete response to phenobarbital, resulting in it being seizure-free long term. FMTs were performed three times, two weeks apart, and the dogs had follow-up visits at three and six months after FMTs. Comprehensive behavioral analysis, including formerly validated questionnaires and behavioral tests for attention deficit hyperactivity disorder (ADHD)- and fear- and anxiety-like behavior, as well as cognitive dysfunction, were conducted, followed by objective computational analysis. Blood samples were taken for the analysis of antiseizure drug (ASD) concentrations, hematology, and biochemistry. Urine neurotransmitter concentrations were measured. Fecal samples were subjected to analysis using shallow DNA shotgun sequencing, real-time polymerase chain reaction (qPCR)-based Dysbiosis Index (DI) assessment, and short-chain fatty acid (SCFA) quantification. Results: Following FMT, the patients showed improvement in ADHD-like behavior, fear- and anxiety-like behavior, and quality of life. The excitatory neurotransmitters aspartate and glutamate were decreased, while the inhibitory neurotransmitter gamma-aminobutyric acid (GABA) and GABA/glutamate ratio were increased compared to baseline. Only minor taxonomic changes were observed, with a decrease in Firmicutes and a Blautia_A species, while a Ruminococcus species increased. Functional gene analysis, SCFA concentration, blood parameters, and ASD concentrations remained unchanged. Discussion: Behavioral comorbidities in canine IE could be alleviated by FMT. This study highlights FMT's potential as a novel approach to improving behavioral comorbidities and enhancing the quality of life in canine patients with epilepsy.

Comparative subcutaneous and submuscular implantation of an electroencephalography device for long term electroencephalographic monitoring in dogs.

Background: Implantable electroencephalography (EEG) recording devices have been used for ultra-long-term epilepsy monitoring both in clinical and home settings in people. Objective and accurate seizure detection and recording at home could be of great benefit in diagnosis, management and research in canine idiopathic epilepsy (IE). Continuous EEG monitoring would allow accurate detection of seizure patterns, seizure cycles, and seizure frequency. An EEG acquisition system usable in an "out of clinic" setting could improve owner and veterinary compliance for EEG diagnostics and seizure management. Objectives: Whether a subcutaneous ultra-long term EEG monitoring device designed for humans could be implanted in dogs. Animals: Cadaver study with 8 medium to large breed dogs. Methods: Comparatively using a subcutaneous and submuscular approach to implant the UNEEG SubQ-Implant in each dog. Positioning was controlled via CT post implantation and cranial measurements were taken. Results: In four of the eight dogs a submuscular implantation without any complications was possible. Complications were close contact to the optic nerve in the first approaches, before the implantation angle was changed and in the smallest dog contact of the implant with the orbital fat body. Cranial measurements of less than 95 mm length proved to be too small for reliable implantation via this approach. The subcutaneous approach showed severe limitations and the implant was prone to dislocation. Conclusion: The UNEEQ SubQ-Implant can be implanted in dogs, via submuscular approach. CT imaging and cranial measurements should be taken prior to implantation.

Canine Electroencephalography Electrode Positioning Using a Neuronavigation System.

BACKGROUND: Studies in people suggest that surface electroencephalography (EEG) electrode positions vary across participants and that the consistency of these positions is electrode-, region-, and examiner-dependent. The aim was to investigate the variability in EEG electrode positions to their underlying cortical regions (CRs) in dogs using a neuronavigation system and evaluate the use of said system in electrode positioning, via a cadaver study with 22 dogs. CT scans and MRI were performed for each dog. These were uploaded onto a neuronavigation system where the desired CRs were annotated. The electrode positions were marked on the heads, which were positioned using only a previously established guide and anatomical landmarks. Using the neuronavigation system, alignment or deviations from the desired CRs were noted. Fifty-three percent of all the marked electrode positions showed an alignment with the desired CRs. Thirty-three percent showed no alignment, and fourteen percent showed partial alignment. Three percent deviated to different cortical lobes. Placement via the neuronavigation system enabled reliable and replicable electrode positioning and CR alignment. The standard for EEG electrode placement in dogs is subjected to a high variance. A neuronavigation system can aid in more precise electrode placements. Specific gyri cannot accurately be evaluated on EEG without imaging-controlled electrode placement.

MicroRNA expression analysis in peripheral blood and soft-tissue of patients with periprosthetic hip infection.

Aims: Current diagnostic tools are not always able to effectively identify periprosthetic joint infections (PJIs). Recent studies suggest that circulating microRNAs (miRNAs) undergo changes under pathological conditions such as infection. The aim of this study was to analyze miRNA expression in hip arthroplasty PJI patients. Methods: This was a prospective pilot study, including 24 patients divided into three groups, with eight patients each undergoing revision of their hip arthroplasty due to aseptic reasons, and low- and high-grade PJI, respectively. The number of intraoperative samples and the incidence of positive cultures were recorded for each patient. Additionally, venous blood samples and periarticular tissue samples were collected from each patient to determine miRNA expressions between the groups. MiRNA screening was performed by small RNA-sequencing using the miRNA next generation sequencing (NGS) discovery (miND) pipeline. Results: Overall, several miRNAs in plasma and tissue were identified to be progressively deregulated according to ongoing PJI. When comparing the plasma samples, patients with a high-grade infection showed significantly higher expression levels for hsa-miR-21-3p, hsa-miR-1290, and hsa-miR-4488, and lower expression levels for hsa-miR-130a-3p and hsa-miR-451a compared to the aseptic group. Furthermore, the high-grade group showed a significantly higher regulated expression level of hsa-miR-1260a and lower expression levels for hsa-miR-26a-5p, hsa-miR-26b-5p, hsa-miR-148b-5p, hsa-miR-301a-3p, hsa-miR-451a, and hsa-miR-454-3p compared to the low-grade group. No significant differences were found between the low-grade and aseptic groups. When comparing the tissue samples, the high-grade group showed significantly higher expression levels for 23 different miRNAs and lower expression levels for hsa-miR-2110 and hsa-miR-3200-3p compared to the aseptic group. No significant differences were found in miRNA expression between the high- and low-grade groups, as well as between the low-grade and aseptic groups. Conclusion: With this prospective pilot study, we were able to identify a circulating miRNA signature correlating with high-grade PJI compared to aseptic patients undergoing hip arthroplasty revision. Our data contribute to establishing miRNA signatures as potential novel diagnostic and prognostic biomarkers for PJI.

Comparing standard screening questionnaires of canine behavior for assessment of cognitive dysfunction.

Background: Canine cognitive dysfunction (CCD) is a common, yet underdiagnosed neurodegenerative disease affecting older dogs. Treatment is most effective when started early, so identifying mild cognitive decline in the earlier stages of the disease is considered important. Hypothesis/objective: To compare the results of three different standard screening questionnaires [Canine Dementia Scale (CADES), Canine Cognitive Assessment Scale (CCAS), and Canine Cognitive Dysfunction Rating Scale (CCDR)] for CCD diagnosis. Trainability, pain sensitivity, and fear were additionally assessed with the Canine Behavioral Assessment and Research Questionnaire (C-BARQ) in order to evaluate associations between the three dementia scales and behavior. Methods: An online survey containing all the mentioned questionnaires was designed for and distributed among owners of elderly dogs. Results: Data from 597 dogs were analyzed. Overall, the scores of the three CCD questionnaires correlated well with each other, especially those of the CADES and CCAS. The CADES was more sensitive in identifying dogs with already mild to moderate cognitive impairment, while the others classified them as still undergoing normal aging. CCD scores increased for all questionnaires with age with spatial orientation being a key feature in CCD development. Trainability assessed with the C-BARQ decreased significantly with severity of CCD signs, while pain sensitivity increased. Fear and anxiety was pronounced in animals with mild but not with severe CCD. These associations based on the C-BARQ were more clearly observable in relation to CADES and CCDR than CCAS. Conclusion/clinical relevance: The choice of screening questionnaire impacts the evaluation of cognitive status and severity of CCD. Thresholds for severity classification differ significantly and may have an impact on reliable assessment. Further longitudinal studies are required to determine which of the questionnaires investigated in this study is best suited for early detection of CCD.

Success Rate After 2-Stage Spacer-Free Total Hip Arthroplasty Exchange and Risk Factors for Reinfection: A Prospective Cohort Study of 187 Patients.

BACKGROUND: Two-stage prosthesis exchange is the treatment of choice for chronic periprosthetic joint infection (PJI) of a total hip arthroplasty (THA), especially when the bone and surrounding soft tissues are compromised or difficult-to-treat pathogens are implicated. The aims of our study were as follows: (1) to determine the outcome of 2-stage prosthesis exchange for the treatment of PJI after THA and (2) to determine the risk factors for reinfection leading to subsequent revision surgeries after reimplantation. METHODS: We prospectively enrolled 187 consecutive patients who underwent a 2-stage THA exchange with resection arthroplasty for PJI from 2013 to 2019. The mean (± SD) duration of follow-up was 54.2 ± 24.9 months (range, 36 to 96), and the mean interval until reimplantation was 9.8 ± 8.9 weeks (range, 2 to 38). All patients remained in a spacer-free girdlestone situation between the 2 stages of treatment. Patients who remained infection-free after their 2-stage treatment were considered to have achieved treatment success. RESULTS: The overall success rate was 85.6%. The cumulative probability of reinfection was 11.5% after one year and 14% after 2 years after reimplantation. High virulence or difficult-to-treat pathogens were significant and independent risk factors for reinfection (HR [hazard ratio] = 3.71, 95% CI [confidence interval]: 1.47 to 9.36, P = .006 and HR = 3.85, 95% CI: 1.73 to 8.57, respectively, P = .001), as was previous 2-stage hip prosthesis exchange (HR = 3.58, 95% CI: 1.33 to 9.62, P = .01). Overall reoperation and revision rates were 26.2 and 16.6%, respectively. Re-infected patients had an 80% higher probability of reoperation than noninfected ones (P < .001, log-rank = 102.6), and they were 55% more likely to undergo revision surgery during their follow-up (P < .001, log-rank = 55.4). CONCLUSIONS: Reinfection rates after 2-stage spacer-free THA revision for PJI still remain high but are comparable to those including cement spacers. Patients who have had prior failed 2-stage implant exchanges or are infected by high-grade or difficult-to-treat pathogens are at high risk for treatment failure.

Re-evaluating the placebo response in recent canine dietary epilepsy trials.

The placebo response is a common phenomenon. Limited evidence is available about its magnitude in canine epilepsy trials, even though it can significantly influence the efficacy evaluation of new treatments. It was hypothesised that the placebo response is diminished when epilepsy trials are conducted in a prospective crossover design. Seizure data spanning six months from three previous multicenter epilepsy studies were analysed. The monthly seizure frequency of 60 dogs diagnosed with idiopathic epilepsy was calculated, comparing baseline data with placebo treatment. Furthermore, differentiation was made between dogs randomised to the placebo group early (Phase 1: first 3 months) or later during the study (Phase 2: second 3 months).The analysis did not reveal any placebo response in terms of monthly seizure frequency. Instead, an increase was noted during the placebo treatment period, with a mean of 2.95 seizures per month compared to 2.30 seizures per month before study entry (p = 0.0378). Additionally, a notable phase effect was observed. Dogs receiving the placebo in the second study phase exhibited a significant increase in monthly seizure frequency compared to baseline (p = 0.0036). Conversely, no significant difference from baseline was observed for dogs receiving the placebo in the first study phase. These findings underscore the considerable variability in placebo responses observed in trials for canine epilepsy, contrasting with previous limited data. The identified phase effect should be carefully considered in the design and evaluation of canine epilepsy trials to ensure a more accurate assessment of efficacy for new treatments.

The Safety and Efficacy of Microporous Polysaccharide Hemospheres in Terms of the Complication Rates in Total Hip Arthroplasty for Femoral Neck Fractures: A Control-Matched Retrospective Cohort.

AIMS: This study aimed to assess the safety and efficacy of microporous polysaccharide hemospheres (MPSHs) in managing blood loss and reducing the risk of postoperative haematoma and early periprosthetic joint infection (PJI) following total hip arthroplasty (THA) for femoral neck fracture (FNF), in the context of the existing treatment challenges. METHODS: A control-matched retrospective analysis of 163 patients undergoing unilateral primary THA for displaced FNF between 2020 and 2023 was performed. The study group consisted of 74 patients who received MPSH administered intraoperatively. The control group consisted of 89 patients who received no topical haemostatics. One-to-one case-control matching between groups was performed. The primary outcome was a perioperative change in the haematologic values (haemoglobin, red blood cell count, haematocrit, platelet concentration) and transfusion rate. The secondary outcomes were the incidence of postoperative local haematoma formation, prolonged wound secretion, surgical site infection (SSI), and PJI within 3 months of surgery. RESULTS: Our analysis found no statistically significant differences in the haematologic parameters between the control and study cohorts. The changes in the haemoglobin concentration were not significant between the control group (3.18 ± 1.0 g/dL) and the treatment group (2.87 ± 1.15 g/dL) (p = 0.3). There were no significant differences (p = 0.24) in the haematocrit and red blood cell concentration (p = 0.15). The platelet levels did not significantly differ (p = 0.12) between the groups. Additionally, we found no significant discrepancy in the incidence of early PJI or blood transfusion rates between the groups. No adverse effects following MPSH use were recorded in the study group. CONCLUSIONS: Routine use of MPSH in THA for FNF management appears to be safe, with no observed adverse events related to Arista® use. Although there was a tendency towards reduced blood loss in the Arista® AH group, MPSH did not significantly impact bleeding complications, local haematoma formation, or subsequent PJI.

Fecal supernatants from dogs with idiopathic epilepsy activate enteric neurons.

Introduction: Alterations in the composition and function of the gut microbiome have been reported in idiopathic epilepsy (IE), however, interactions of gut microbes with the enteric nervous system (ENS) in this context require further study. This pilot study examined how gastrointestinal microbiota (GIM), their metabolites, and nutrients contained in intestinal contents communicate with the ENS. Methods: Fecal supernatants (FS) from healthy dogs and dogs with IE, including drug-naïve, phenobarbital (PB) responsive, and PB non-responsive dogs, were applied to cultured myenteric neurons to test their activation using voltage-sensitive dye neuroimaging. Additionally, the concentrations of short-chain fatty acids (SCFAs) in the FS were quantified. Results: Our findings indicate that FS from all examined groups elicited neuronal activation. Notably, FS from PB non-responsive dogs with IE induced action potential discharge in a higher proportion of enteric neurons compared to healthy controls, which exhibited the lowest burst frequency overall. Furthermore, the highest burst frequency in enteric neurons was observed upon exposure to FS from drug-naïve dogs with IE. This frequency was significantly higher compared to that observed in PB non-responsive dogs with IE and showed a tendency to surpass that of healthy controls. Discussion: Although observed disparities in SCFA concentrations across the various FS samples might be associated with the induced neuronal activity, a direct correlation remains elusive at this point. The obtained results hint at an involvement of the ENS in canine IE and set the basis for future studies.

ChatGPT May Offer an Adequate Substitute for Informed Consent to Patients Prior to Total Knee Arthroplasty-Yet Caution Is Needed.

Prior to undergoing total knee arthroplasty (TKA), surgeons are often confronted with patients with numerous questions regarding the procedure and the recovery process. Due to limited staff resources and mounting individual workload, increased efficiency, e.g., using artificial intelligence (AI), is of increasing interest. We comprehensively evaluated ChatGPT's orthopedic responses using the DISCERN instrument. Three independent orthopedic surgeons rated the responses across various criteria. We found consistently high scores, predominantly exceeding a score of three out of five in almost all categories, indicative of the quality and accuracy of the information provided. Notably, the AI demonstrated proficiency in conveying precise and reliable information on orthopedic topics. However, a notable observation pertains to the generation of non-existing references for certain claims. This study underscores the significance of critically evaluating references provided by ChatGPT and emphasizes the necessity of cross-referencing information from established sources. Overall, the findings contribute valuable insights into the performance of ChatGPT in delivering accurate orthopedic information for patients in clinical use while shedding light on areas warranting further refinement. Future iterations of natural language processing systems may be able to replace, in part or in entirety, the preoperative interactions, thereby optimizing the efficiency, accessibility, and standardization of patient communication.

Epilepsy is more than a simple seizure disorder: Parallels between human and canine cognitive and behavioural comorbidities.

Psychiatric and cognitive comorbidities have been known to play a major role in human epilepsy for a long time. People with epilepsy (PWE) frequently express signs of varying psychiatric and cognitive disorders affecting their quality and quantity of life (QoL/QaoL). Over the last few years, research on behavioural comorbidities and their effect on the underlying disease have been performed in canine epilepsy. The following article reviews manifestations of comorbidities in canine epilepsy with an emphasis on patterns of clinical signs and their effects on QoL and QaoL. Cognitive and behavioural alterations in epileptic dogs are mainly represented by fear-/anxiety related behaviour and cognitive impairment (CI). Reduced trainability and altered reactions to daily situations are common results of comorbid changes posing obstacles in everyday life of owners and their dog. In addition, clinical signs similar to attention deficit hyperactivity disorder (ADHD) in humans have been reported. Canine attention-deficit-hyperactivity-disorder-like (c-ADHD-like) behaviour should, however, be evaluated critically, as there are no official criteria for diagnosis of ADHD or ADHD-like behaviour in dogs, and some of the reported signs of c-ADHD-like behaviour could be confused with anxiety-associated behaviour. Many intrinsic and extrinsic factors could potentially influence the development of behavioural and cognitive comorbidities in canine epilepsy. In particular, seizure frequency/severity, signalment and factors concerning disease management, such as pharmacotherapy and nutrition, are closely linked with the presence of the aforementioned comorbid disorders. Further studies of behavioural alterations in epileptic dogs are needed to comprehend the complexity of clinical signs and their multifactorial origin.

Epilepsy is more than a simple seizure disorder: Causal relationships between epilepsy and its comorbidities.

This review draws connections between the pathogenesis of canine epilepsy and its most commonly recognised comorbidities: cognitive impairment (CI), attention deficit hyperactivity disorder (ADHD)-like behaviour, fear and anxiety. Uni/bidirectional causalities and the possibility of a common aetiology triggering both epilepsy and the associated diseases are considered. Research on this topic is sparse in dogs, so information has been gathered and assessed from human and laboratory animal studies. Anatomical structures, functional connections, disrupted neurotransmission and neuroinflammatory processes collectively serve as a common foundation for epilepsy and its comorbidities. Specific anatomical structures, especially parts of the limbic system, such as the amygdala and the hippocampus, are involved in generating seizures, as well as cognitive- and behavioural disorders. Furthermore, disturbances in inhibitory and excitatory neurotransmission influence neuronal excitability and networks, leading to underlying brain dysfunction. Functional magnetic resonance imaging (fMRI), interictal epileptiform discharges (IEDs), and electroencephalography (EEG) have demonstrated functional brain connections that are related to the emergence of both epilepsy and its various comorbidities. Neuroinflammatory processes can either cause or be a consequence of seizures, and inflammatory mediators, oxidative stress and mitochondrial dysfunction, can equally evoke mood disorders. The extensive relationships contributing to the development and progression of seizures and comorbid cognitive and behavioural conditions illustrate the complexity of the disease that is epilepsy.

Virtual non-contrast images of detector-based spectral computed tomography in dogs: a promising alternative to true non-contrast images in veterinary medicine.

Introduction: In veterinary medicine, abdominal computer tomographic (CT) examinations regularly require a minimum of two scans, with a native scan (true unenhanced, TUE) as a reference for the subsequent contrast-enhanced CT scan (CECT). Spectral detector CT (SDCT) offers the possibility to calculate virtual non-contrast (VNC) images from the post-contrast scan, but this has not yet been investigated in veterinary medicine. The purpose of this study was to assess the reliability of VNC images for abdominal organs in 44 dogs without abdominal pathologies by evaluating their quantitative and qualitative parameters compared to TUE images. We hypothesized that the subtraction of iodine is sufficient in the VNC series compared to the TUE series and that the image quality of the SDCT series is superior to conventional CT images. Methods: Corresponding attenuation values in the VNC and TUE series regarding the regions of interest (ROI) in different parenchymal organs and major vessels of the abdominal cavity were assessed by means of a two one-sided t-test (TOST) and Bland-Altman plots. Additionally, the signal-to-noise ratio (SNR) was calculated for each ROI in the different series. In the second step, two board-certified veterinary radiologists made a qualitative assessment of VNC images vs. TUE images in consensus by rating the iodine subtraction, image noise, and image quality of VNC images based on a specific 5-point Likert scale. Results: The difference in corresponding Hounsfield units (HUs) between TUE and VNC images was less than 10 HU in 78.67% of all ROIs. Regarding the limit of less than 10 HU, in the performed TOST, significant p-values of < 0.05 were reached for the liver, spleen, pancreas, and musculature, implying equivalence of both modalities. The quality of spectral base image (SBI) data was rated equivalent to calculated conventional images in the subjective assessment by reaching an average Likert scale score of 3.2 points. Discussion: VNC images calculated from SDCT data prove a valid alternative to conventional TUE images in the abdominal organs of canine patients without abdominal pathology. VNC offers the possibility to reduce time under general anesthesia and minimize radiation exposure. Future studies are needed to prove the application of this method in clinically diseased patients.

Adverse Events Associated with Prolonged Antibiotic Therapy for Periprosthetic Joint Infections-A Prospective Study with a Special Focus on Rifampin.

Periprosthetic Joint Infection (PJI) is a significant contributor to patient morbidity and mortality, and it can be addressed through a range of surgical interventions coupled with antibiotic therapies. Following surgical intervention(s), prolonged administration of oral antibiotics is recommended to cure PJI. There is a lack of reports on the adverse events (AEs) associated with oral antibiotics, particularly rifampin. This investigation sought to elucidate the occurrence of antibiotic-related AEs after an initial regimen of intravenous antibiotic administration, supplemented by an extended course of oral antibiotics. A prospective study of patients diagnosed with PJI of the hip, knee, or shoulder who underwent single-stage exchange arthroplasty (SSE) (10%), two-stage exchange arthroplasty (TSE) (81%), or debridement, antibiotics, and implant retention (DAIR) (6%) was performed. The primary outcome of interest was the detection of AEs, the secondary outcome the detection of a correlation between rifampin use and the incidence of AEs, and the tertiary outcome was whether oral antibiotic treatment needed to be adjusted or discontinued due to AEs. In addition, subjective tolerability was monitored throughout the study. A total of 336 events were identified for 73 out of 80 patients. The most frequently used antibiotics were rifampin and co-trimoxazole. Most AEs occurred in the gastrointestinal tract (46%). The most frequent AEs were nausea, inappetence, diarrhea, and skin rash. In 6% of cases, the AEs led to antibiotic discontinuation, and in 29% of cases, a dose adjustment of the oral therapy occurred, mainly with amoxicillin or co-trimoxazole. The majority of patients (55%) rated the subjective tolerability as good. In conclusion, AEs during antibiotic treatment for PJI are common. They mainly affect the gastrointestinal tract. Rifampin use might be a reason for the higher incidence of AEs compared to non-rifampin antibiotic treatment.

Evaluation of the Submaximal Treadmill-Based Fitness Test in Six Brachycephalic Breeds-A Follow-Up Study.

Brachycephalic obstructive airway syndrome (BOAS) in dogs challenges veterinary surgeons both with a complex clinical picture as well as wide-ranging ways to diagnose the disease, often not easily implemented nor standardised in clinical practice. The assessment of a combination of exercise testing, the occurrence of breathing noises, recovery time, and respiratory effort proved to be an appropriate method to identify Pugs with BOAS. The purpose of this study was to apply an established standardised, submaximal, treadmill-based fitness test for Pugs to other brachycephalic dog breeds. A total of 79 participants, belonging to 6 different brachycephalic breeds, trotted 15 min with an individual comfort speed of 3-7 km/h on a treadmill. Additionally, functional BOAS grading based on respiratory clinical signs before and after exercise was applied. The test was passed if the dogs presented with a BOAS grade of 0 or 1 and their vital parameters recovered to baseline within 15 min after exercise. A total of 68% showed a BOAS grade of 0 or 1 and passed the fitness test. Of the failed participants, 65% failed due to BOAS affectedness, 9% were categorised as not affected by BOAS and failed due to not passing the fitness test only, and 26% showed both failure criteria. The fitness test can be a useful method to identify BOAS-affected dogs in other brachycephalic breeds and to diagnose BOAS in dogs that only show clinical signs under exercise.

BrachySound: machine learning based assessment of respiratory sounds in dogs.

The early and accurate diagnosis of brachycephalic obstructive airway syndrome (BOAS) in dogs is pivotal for effective treatment and enhanced canine well-being. Owners often do underestimate the severity of BOAS in their dogs. In addition, traditional diagnostic methods, which include pharyngolaryngeal auscultation, are often compromised by subjectivity, are time-intensive and depend on the veterinary surgeon's experience. Hence, new fast, reliable assessment methods for BOAS are required. The aim of the current study was to use machine learning techniques to bridge this scientific gap. In this study, machine learning models were employed to objectively analyze 366 audio samples from 69 Pugs and 79 other brachycephalic breeds, recorded with an electronic stethoscope during a 15-min standardized exercise test. In classifying the BOAS test results as to whether the dog is affected or not, our models achieved a peak accuracy of 0.85, using subsets from the Pugs dataset. For predictions of the BOAS results from recordings at rest in Pugs and various brachycephalic breeds, accuracies of 0.68 and 0.65 were observed, respectively. Notably, the detection of laryngeal sounds achieved an F1 score of 0.80. These results highlight the potential of machine learning models to significantly streamline the examination process, offering a more objective assessment than traditional methods. This research indicates a turning point towards a data-driven, objective, and efficient approach in canine health assessment, fostering standardized and objective BOAS diagnostics.

Long-lasting antiseizure effects of chronic intrasubthalamic convection-enhanced delivery of valproate.

Intracerebral drug delivery is an experimental approach for the treatment of drug-resistant epilepsies that allows for pharmacological intervention in targeted brain regions. Previous studies have shown that targeted pharmacological inhibition of the subthalamic nucleus (STN) via modulators of the GABAergic system produces antiseizure effects. However, with chronic treatment, antiseizure effects are lost as tolerance develops. Here, we report that chronic intrasubthalamic microinfusion of valproate (VPA), an antiseizure medication known for its wide range of mechanisms of action, can produce long-lasting antiseizure effects over three weeks in rats. In the intravenous pentylenetetrazole seizure-threshold test, seizure thresholds were determined before and during chronic VPA application (480 µg/d, 720 µg/d, 960 µg/d) to the bilateral STN. Results indicate a dose-dependent variation in VPA-induced antiseizure effects with mean increases in seizure threshold of up to 33%, and individual increases of up to 150%. The lowest VPA dose showed a complete lack of tolerance development with long-lasting antiseizure effects. Behavioral testing with all doses revealed few, acceptable adverse effects. VPA concentrations were high in STN and low in plasma and liver. In vitro electrophysiology with bath applied VPA revealed a reduction in spontaneous firing rate, increased background membrane potential, decreased input resistance and a significant reduction in peak NMDA, but not AMPA, receptor currents in STN neurons. Our results suggest an advantage of VPA over purely GABAergic modulators in preventing tolerance development with chronic intrasubthalamic drug delivery and provide first mechanistic insights in intracerebral pharmacotherapy targeting the STN.