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Abstract Background Before the discovery of effective antiviral drugs, feline infectious peritonitis (FIP) was a uniformly fatal disease of cats. Multiple antiviral treatments have been recognized, but optimization of treatment protocols is needed. Objective To evaluate the efficacy of PO molnupiravir (MPV; EIDD‐2801) to treat effusive FIP. Animals Ten cats with naturally occurring effusive FIP and 10 historical control cats with effusive FIP treated with PO GS‐441524. Methods A single‐center, prospective, open‐label longitudinal, non‐inferiority trial with historical controls. Ten cats with FIP were enrolled and treated with PO MPV (10‐15 mg/kg PO q12h) for 84 days. Cats were evaluated at 0, 6, and 16 weeks, and the proportion of cats in clinical remission at 16 weeks was determined. Survival and clinicopathologic features were compared with historical control cats with effusive FIP treated with PO GS‐441524. Results Eight of the 10 cats treated with MPV survived and were in remission at 16 weeks. The 2 non‐survivors died in the first 24 hours of treatment. No adverse events that necessitated discontinuation of treatment were observed. Survival of cats treated with PO MPV was non‐inferior to historic control cats treated with PO GS‐441524 (5/9 [55%] survived), with a difference in survival of 25% (90% confidence interval, −9.3% to 59.3%). Clinicopathologic features associated with FIP normalized during the study period, and no differences in clinicopathologic data at each study time point were observed when comparing cats treated with MPV and GS‐441524. Conclusions and Clinical Importance Molnupiravir is an effective antiviral treatment for effusive FIP.

Abstract Background Recurrent bacterial cystitis, often referred to as recurrent urinary tract infection (UTI), can be difficult to manage and alternative treatments are needed. Hypothesis/Objective Intravesicular administration of asymptomatic bacteriuria (ASB) E. coli 212 will not be inferior to antimicrobial treatment for the management of recurrent UTI in dogs. Animals Thirty‐four dogs with >1 UTI in the 12 months before presentation. Methods All dogs were deemed normal otherwise based on absence of abnormalities on physical examination, CBC, serum biochemical panel, and abdominal ultrasonography. Dogs were randomized to 1 of 2 treatment groups: Group 1 antimicrobials for 7 days or group 2 intravesicular administration of ASB E. coli 212. Owners were provided a voiding questionnaire regarding their dogs' clinical signs, which was completed daily for 14 days to assess clinical cure. Dogs were examined on days 7 and 14 to assess clinical cure, and urine specimens were submitted for urinalysis and bacterial culture. Results Clinical cure rates for ASB E. coli 212–treated dogs were not inferior to 7 days of antimicrobial treatment with a 12% margin of difference to determine non‐inferiority. No significant difference was found between the treatment groups on days 7 and 14 in the proportion of dogs achieving ≥50% or ≥75% reduction in their clinical score compared with baseline. Conclusions and Clinical Importance These data suggest that intravesicular administration of ASB E. coli 212 is not inferior to antimicrobials for the treatment of recurrent UTI in dogs. This biotherapeutic agent could help alleviate the need for antimicrobials for some dogs with recurrent UTI, improving antimicrobial stewardship.

Abstract Background The ability to detect bacteriuria in dogs with a point‐of‐care test might improve medical care and antimicrobial stewardship. Hypothesis and Objective A rapid immunoassay (RIA; RapidBac) will provide acceptable sensitivity and specificity for diagnosis of bacteriuria. Animals Forty‐four client‐owned dogs with a clinical indication for urinalysis and aerobic bacterial urine culture. Methods Prospective study. Urine, collected by cystocentesis, was submitted for urinalysis and culture at a diagnostic laboratory. Owners completed an enrollment questionnaire regarding their dogs' clinical signs. The RIA was performed according to the manufacturer's guidelines. Results were compared to culture. Results Forty‐four urine specimens were evaluated from 44 dogs. The sensitivity and specificity of the RIA test to detect bacteriuria compared to urine culture were 81.8% (95% CI, 65.7%‐97.9%) and 95.5% (95% CI, 86.8%‐99.9%), respectively. For cultures yielding ≥103 CFU/mL, sensitivity increased to 90.0% (95% CI, 76.9%‐100%) and specificity was similar at 95.2% (95% CI, 86.1%‐99.9%). Malodorous urine, bacteriuria, and pyuria were more likely to be present in dogs with positive RIA or urine culture results compared to dogs with negative results. Conclusions and Clinical Importance The RIA was easy to perform and had good sensitivity and excellent specificity in this group of dogs. The RIA might be a useful screening test for decision‐making regarding antimicrobial therapy in dogs with a clinical indication for urine culture. Consideration could be given to amending the International Society for Companion Animal Infectious Disease definition of bacterial cystitis as the presence of signs of lower urinary tract disease together with positive culture or a positive RIA.

Abstract Background Dogs with hypoadrenocorticism (HA) have clinical signs and clinicopathologic abnormalities that can be mistaken as other diseases. In dogs with a differential diagnosis of HA, a machine learning model (MLM) has been validated to discriminate between HA and other diseases. This MLM has not been evaluated as a screening tool for a broader group of dogs. Hypothesis An MLM can accurately screen dogs for HA. Animals Dogs (n = 1025) examined at a veterinary hospital. Methods Dogs that presented to a tertiary referral hospital that had a CBC and serum chemistry panel were enrolled. A trained MLM was applied to clinicopathologic data and in dogs that were MLM positive for HA, diagnosis was confirmed by measurement of serum cortisol. Results Twelve dogs were MLM positive for HA and had further cortisol testing. Five had HA confirmed (true positive), 4 of which were treated for mineralocorticoid and glucocorticoid deficiency, and 1 was treated for glucocorticoid deficiency alone. Three MLM positive dogs had baseline cortisol ≤2 μg/dL but were euthanized or administered glucocorticoid treatment without confirming the diagnosis with an ACTH‐stimulation test (classified as “undetermined”), and in 4, HA was ruled out (false positives). The positive likelihood ratio of the MLM was 145 to 254. All dogs diagnosed with HA by attending clinicians tested positive by the MLM. Conclusions and Clinical Importance This MLM can robustly predict HA status when indiscriminately screening all dogs with blood work. In this group of dogs with a low prevalence of HA, the false positive rates were clinically acceptable.

Abstract Background For the treatment of diabetes mellitus (DM) in dogs, novel insulins with decreased injection frequency while maintaining safety and efficacy are desirable. Insulin fused with immunoglobulin‐fragment‐crystallizable (Fc) has an ultra‐long plasma half‐life because it recycles through cells, protected from proteolysis. Hypothesis Glycemic control can be achieved in diabetic dogs with a recombinant fusion protein of a synthetic insulin and canine Fc (AKS‐218d) administered subcutaneously once‐weekly. Animals Five client‐owned dogs with naturally occurring DM. Methods Prospective clinical trial in dogs with DM that were recruited from the UC Davis Veterinary Teaching Hospital and local veterinary clinics. Dogs previously controlled using intermediate‐acting insulin q12h were transitioned to once‐weekly injections of a preliminary construct identified as AKS‐218d. The dose of AKS‐218d was titrated weekly for 8 weeks based on clinical response and continuous interstitial glucose monitoring. Clinical signs, body weight, serum fructosamine concentrations, and mean interstitial glucose concentrations (IG) over the preceding week were compared between baseline (before AKS‐218d) and during the last week of treatment. Data were compared using nonparametric paired tests. Results Once‐weekly AKS‐218d, compared to baseline twice‐daily insulin therapy, resulted in no significant changes in clinical signs, median (range) body weight (+0.4 kg [−0.5‐1.1]; P = .6), fructosamine concentration (−75 mmol/L [−215 to +126]; P = .4), or mean IG (+81 mg/dL [−282 to +144]; P = .8). No adverse reactions were reported. Conclusion Control of clinical signs, body weight, and maintenance of glycemia was achieved with this once‐weekly novel insulin construct in 4 of 5 dogs.

Nucleoside analogs GS-441524 and remdesivir (GS-5734) are effective in treating cats with feline infectious peritonitis (FIP). However, no studies have compared the efficacy between antiviral medications. The objective of this study was to evaluate the efficacy of orally administered GS-442514 (12.5–15 mg/kg) compared to orally administered remdesivir (25–30 mg/kg) in a double-blinded non-inferiority trial. Eighteen cats with effusive FIP were prospectively enrolled and randomly assigned to receive either GS-442514 or remdesivir. Cats were treated daily for 12 weeks and evaluated at week 0, 12, and 16. Survival and disease remission at week 16 were compared between groups. Five of 9 (55%) cats treated GS-441524 and 7/9 (77%) cats treated with remdesivir survived, with no difference in survival rate (p = 0.2). Remdesivir fulfilled the criteria for non-inferiority with a difference in survival of 22% (90% CI; −13.5–57.5%). Three of the 18 cats died within 48 h of enrollment. Excluding these cats, 5/6 (83%) of the cats treated with GS-441524 and 7/9 (77%) of the cats treated with remdesivir survived. These findings suggest that both orally administered GS-441524 and remdesivir are safe and effective anti-viral medications for the treatment of effusive FIP. Further optimization of the first 48 h of treatment is needed.

Abstract Background Treatment of diabetes mellitus (DM) in cats typically requires insulin injections q12h‐q24h, posing a major compliance barrier for caregivers. Novel treatments enabling decreased injection frequency while maintaining safety are highly desirable. Insulin fused with feline immunoglobulin fragment crystallizable (Fc) has an ultra‐long plasma half‐life because it recycles through cells where it is protected from proteolysis. Hypothesis Glycemic control can be achieved in diabetic cats with a recombinant fusion protein of a synthetic insulin and feline Fc (AKS‐267c) administered SC weekly. Animals Five cats with spontaneous DM. Methods Cats previously controlled using insulin glargine q12h were transitioned to once‐weekly injection of AKS‐267c. The dose of AKS‐267c was titrated weekly for 7 weeks based on continuous glucose monitoring. Clinical signs, body weight, fructosamine concentrations, and mean interstitial glucose concentrations (IG) were compared between baseline (week 0, on insulin glargine) and the last week of treatment. Data were assessed for normality and compared using parametric or nonparametric paired tests (as appropriate). Results After 7 weeks of once‐weekly injections, compared to baseline, there were no significant changes in clinical signs, body weight (median [range] gain, 0.1 kg [−0.1 to +0.7]; P = .5), fructosamine (−60 mmol/L [−338 to +206]; P = .6), and mean IG concentrations (change = −153 mmol/L [−179 to +29]; P = .3), and no adverse reactions were reported. Conclusion Successful control of clinical signs and maintenance of glycemia was achieved with this once‐weekly novel insulin treatment. The efficacy and safety of this novel formulation should be further assessed in a large clinical trial.

Abstract Background Day‐to‐day variability impacts safety of insulin therapy and the choice of monitoring strategies. Side‐by‐side comparisons of insulin formulations in diabetic dogs are scarce. Hypothesis/Objectives Insulin glargine 300 U/mL (IGla300) and insulin degludec (IDeg) are associated with less day‐to‐day glucose variability compared to porcine lente (PL) in diabetic dogs. Animals Seven intact male purpose‐bred beagles with toxin‐induced diabetes. Methods In this repeated measured study, PL, IGla300 and IDeg were compared in 2 phases: once‐daily (q24h) and twice‐daily (q12h) administration. Interstitial glucose concentrations (IG) were measured continuously throughout the study. For each formulation, maximal q24h dose was determined using the same algorithm (while avoiding hypoglycemia) and then maintained for 72 hours. In phase 2, 70% of the maximal q24h dose was administered q12h and maintained for 5 days regardless of hypoglycemia. Coefficient of variation (CV) and glycemic variability percentage (GVP) were calculated to determine day‐to‐day and intraday variability, respectively. Results There was no difference in day‐to‐day variability between PL, IGla300, and IDeg in the q24h phase. In the q12h phase, day‐to‐day variability was higher (P = .01) for PL (CV = 42.6 ± 6.8%) compared to IGla300 and IDeg (CV = 30.1 ± 7.7%, 25.2 ± 7.0%, respectively). The GVP of PL was lower (P = .02) compared to IGla300. There was no difference between PL, IGla300 and IDeg in %time IG

Abstract Diabetes mellitus (DM) is associated with a dysfunctional intestinal barrier and an increased risk for systemic infection and inflammation in people, though the pathogenic mechanisms leading to this are poorly understood. Using a canine model of DM, we showed that the peroxisomal proliferator-activated receptor-α agonist fenofibrate modulates plasma lipid profiles and markers of intestinal barrier function. A 3-week course of fenofibrate reduced fasting interstitial glucose and inflammatory cytokine IL-8 and TNF-α concentrations, which correlated with reduced triglyceride levels. The lipidomic profile exhibited significantly lower levels of triacylglycerols, phosphatidylethanolamines, diacylglycerols, and ceramides following fenofibrate administration. On histopathological analysis, we observed an aberrant amount of intraepithelial CD3+ T lymphocytes (IEL) in the small intestine of dogs with spontaneous and induced-DM. Fenofibrate reduced IEL density in the duodenum of dogs with DM and enhanced markers of intestinal barrier function in vivo and in vitro. There were minimal changes in the intestinal microbial composition following fenofibrate administration, suggesting that repair of intestinal barriers can be achieved independently of the resident microbiota. Our findings indicate that lipid metabolism is critical to functionality of the intestinal epithelium, which can be rescued by PPARα activation in dogs with DM.

Abstract Background The FreeStyle Libre (Abbott Laboratories) is a flash glucose monitoring system (FGMS) that measures interstitial glucose concentration (IG). The system is factory‐calibrated, easy to use, inexpensive, and could be useful for monitoring diabetic cats. Objectives To evaluate the analytical and clinical accuracy of the FGMS in cats and establish the lag‐time between IG and blood glucose concentration (BG). Animals Twenty client‐owned diabetic cats and 7 purpose‐bred healthy cats. Methods Prospective study. Blood glucose concentration was measured using a portable glucose meter validated for use in cats that served as a reference method for IG, as measured by FGMS. In diabetic cats, data were collected for sensor wearing time with different methods of application and accuracy across glycemic ranges. Accuracy was determined by fulfillment of ISO15197:2013 criteria. In healthy cats, lag‐time between IG and BG was established after IV administration of exogenous glucose. Results Good agreement between IG and BG was obtained (r = .93). Analytical accuracy was not achieved, whereas clinical accuracy was demonstrated with 100% of the results in zones A + B of the Parkes consensus error grid analysis. In the immediate 30 minutes after an IV bolus of glucose, when BG was increasing rapidly (approximately 2%/min), IG increased slowly, resulting in a difference of as much as 579 mg/dL, and no positive correlation between BG and IG was found. Conclusions and Clinical Importance The FGMS did not fulfill ISO requirements but is sufficiently accurate for glucose monitoring in cats, while considering the lag between IG and BG during periods of rapid changes in BG.