Improving access to advanced veterinary care for rescued cats and dogs.

OBJECTIVES: The objectives of this study were as follows: (1) to describe the AMC to the Rescue (AMCTTR) funding criteria and the application process; (2) to describe the distribution of species cared for through the program, the medical conditions treated in cats compared with those treated in dogs and the cost of that care; and (3) to define the successes and challenges of the program. METHODS: The AMCTTR database was reviewed for applications submitted between 1 January 2020 and 31 December 2022. Data collected included the following: the date of application; rescue organization seeking financial support; species; age of pet at time of application; expenditures funded by AMCTTR; and the method by which the rescue organization learned about AMCTTR. The animals in the AMCTTR database were sorted into two groups: those accepted for funding and those that did not meet funding criteria. The Animal Medical Center (AMC) medical record system was searched for the total number of individual animals, species and age seen at AMC during the study period. RESULTS: In total, 267 applications were reviewed and 190 applications from 134 cats, 52 dogs and four rabbits were accepted for advanced veterinary care funded by AMCTTR. Over the 3-year study period, US$612,564 were awarded and over half of those funds were awarded to cats. The average expenditure per animal during this time period was US$3224. The most common referrals to AMCTTR were made to ophthalmology, surgery and dentistry. CONCLUSIONS AND RELEVANCE: The needs of cats differed from dogs in that feline applications were most commonly submitted for ophthalmology or dentistry. Expenditures per cat were less than per dog because dogs were referred for more expensive orthopedic surgery. The need for advanced veterinary care for rescue animals is enormous, especially for cats. Programs that subsidize advanced veterinary care increase access to that care.

Proof-of-Concept Study of an Alpha-Fetoprotein-Derived Peptide for the Management of Canine Mammary Cancer.

Novel, well-tolerated drugs are needed for the management of canine mammary cancer. Many of these cancers are promoted in their growth by estrogen. Alpha-fetoprotein (AFP) is a ubiquitous mammalian protein that has anti-estrogenic properties. AFPep (the anti-estrogenic site of AFP) has been developed into a readily synthesizable drug. AFPep has been shown to have anti-mammary cancer activity in several models of this disease, both in cell culture and in rodents. The purpose of the study reported herein was to determine the tolerability of AFPep in normal and tumor-bearing dogs. AFPep was given to dogs via both parenteral and oral routes in a single application and in repeated daily doses. Full clinical chemistry and hematology values were determined before and after drug administration. Blood levels of the drug were achieved in dogs that had been previously found to be oncostatic in rodents. No changes in clinical chemistry, hematology, and clinical behaviors were found in dogs following drug administration. The data support the further development of AFPep for clinical use against canine mammary cancer.

Toxicity, outcome, and management of anthracycline overdoses in 16 dogs.

BACKGROUND: Despite multiple reports of chemotherapy overdoses (ODs) in human and veterinary medicine, anthracycline ODs have been described infrequently. HYPOTHESIS/OBJECTIVES: Describe toxicities, treatments, and overall outcome after anthracycline OD in dogs. ANIMALS: Twelve mitoxantrone (MTX) and 4 doxorubicin (DOX) ODs were evaluated. METHODS: Multicenter retrospective analysis. The American College of Veterinary Internal Medicine oncology and internal medicine listservs were solicited for cases in which a chemotherapy OD occurred. RESULTS: Sixteen anthracycline cases were collected. Anthracycline ODs occurred because of an error in chemotherapy preparation (n = 9), or dose miscalculation (n = 7). The overall median OD was 1.9× (range, 1.4-10×) the prescribed amount. Most ODs were identified immediately after drug administration (n = 11), and the majority of patients were hospitalized on supportive care (n = 11) for an average of 8 days (range, 3-34 days). Adverse events after the OD included neutropenia (94%), thrombocytopenia (88%), anemia (63%), diarrhea (63%), anorexia (56%), vomiting (38%), lethargy (31%), and nausea (25%). Two patients did not survive the OD. High grade neutropenia was common and did not appear to be mitigated by the administration of filgrastim. CONCLUSIONS AND CLINICAL IMPORTANCE: All patients received supportive care after identifying the OD and death was uncommon. Further evaluation is needed to determine ideal therapeutic guidelines anthracycline OD.

Safety and efficacy of a ribose-cysteine supplement to increase erythrocyte glutathione concentration in healthy dogs.

OBJECTIVE: To evaluate the safety of oral administration of a d-ribose-l-cysteine (RibCys) supplement to dogs and the effect of this supplementation on erythrocyte glutathione (GSH) concentration. ANIMALS: 24 healthy adult dogs. PROCEDURES: In a randomized, double-blinded, controlled trial, dogs received 500 mg of a RibCys supplement or placebo (n = 12/group), PO, every 12 hours for 4 weeks. Dogs were evaluated weekly by means of a physical examination, CBC, serum biochemical analysis, urinalysis, and owner-completed quality-of-life questionnaire. Erythrocyte GSH concentration was measured on day 0 (ie, the day before treatment began) and weekly during supplementation. RESULTS: No dose-limiting adverse effects were noted in any dog. Two dogs in each group had mild, self-limiting diarrhea and anemia. No significant increase in erythrocyte GSH concentration was noted in either group at any time point. Two dogs in the RibCys group had improved skin and coat health and improved clinical signs of osteoarthritis. No clinical or owner-perceived improvements were noted in the placebo group. CONCLUSIONS AND CLINICAL RELEVANCE: The RibCys supplement was safe and well tolerated in all dogs. Owners reported improvements in dermatologic and orthopedic conditions in some dogs in the RibCys group. No significant differences were observed in erythrocyte GSH concentration before or after RibCys treatment. This lack of significant differences may have been attributable to the use of healthy dogs, which would not be expected to have depleted GSH concentrations. Given the observed safety profile of RibCys, additional research is warranted to explore the potential usefulness of RibCys supplementation in dogs with cancer and those undergoing treatment for cancer.

Incidence and treatment of feline renal lymphoma: 27 cases.

OBJECTIVES: Lymphoma is the most common feline hematopoietic malignancy. Incidence of renal lymphoma has not been reported as a subset of a large population of feline lymphoma cases. Previous studies have reported renal lymphoma as both a singular entity as well as a component of multicentric disease. The clinical presentation, diagnostic evaluation, therapy and outcomes related to renal lymphoma have not been reported since Mooney et al in 1987. This retrospective study aimed to describe the incidence of renal lymphoma, clinical signs, treatment and survival. METHODS: Using a database of cats diagnosed with lymphoma between January 2008 and October 2017, cats with renal lymphoma were selected for further analysis. Cases were retrospectively staged according to Mooney et al (1987) and Gabor et al (1998). Data collected included age, clinical signs, clinicopathologic data, diagnostic imaging findings, lymphoma diagnostic method(s), treatment protocol(s) and survival time. Analyses comparing median survival based on therapy administered, renal lymphoma vs multicentric lymphoma, central nervous system involvement, presence of azotemia, anemia and International Renal Interest Society (IRIS) stage at diagnosis were performed. RESULTS: From a population of 740 cats with lymphoma, 27 cats had renal lymphoma (incidence, 3.6%), and 14 of those cats had multicentric lymphoma. Fewer stage IV and V cases were identified in this data set compared with Mooney et al; however, not all cats were completely staged. Median survival (range) for cats receiving corticosteroids alone compared with those receiving an L-CHOP (L-asparaginase, vincristine, cyclophosphamide, doxorubicin, prednisolone)-based protocol was 50 days (20-1027 days) in the corticosteroid group and 203 days (44-2364 days) for the L-CHOP group (P = 0.753) for cats that died secondary to lymphoma. CONCLUSIONS AND RELEVANCE: Neither clinical stage nor other factors were predictive of survival. Prospective studies are required to determine the optimal chemotherapy protocol.

Feline non-regenerative anemia: Diagnostic and treatment recommendations.

PRACTICAL RELEVANCE: Non-regenerative anemia, or anemia with reticulocytopenia, is a daily diagnosis in feline practice. CLINICAL CHALLENGES: The disease processes underlying non-regenerative anemia are many and diverse. A major diagnostic evaluation may be required to correctly diagnose and treat the underlying cause. AUDIENCE: All veterinarians caring for cats will face the diagnostic and therapeutic challenge of non-regenerative anemia. Readers will benefit from the review of diagnostic testing and therapeutic options for non-regenerative anemia. EVIDENCE BASE: This review summarizes the currently available literature informing diagnostic and treatment recommendations related to non-regenerative anemia. The evidence available to support the recommendations in this review is graded as low and includes predominantly expert opinion, case reports and cases series, on which the authors' interpretation/consensus is based.

A comparison of risk factors for metastasis at diagnosis in humans and dogs with osteosarcoma.

BACKGROUND: Canine osteosarcoma (OS) is a relevant spontaneous model for human OS. Identifying similarities in clinical characteristics associated with metastasis at diagnosis in both species may substantiate research aimed at using canine OS as a model for identifying mechanisms driving distant spread in the human disease. METHODS: This retrospective study included dog OS cases from three academic veterinary hospitals and human OS cases from the Surveillance, Epidemiology, and End Results program. Associations between clinical factors and metastasis at diagnosis were estimated using logistic regression models. RESULTS: In humans, those with trunk tumors had higher odds of metastasis at diagnosis compared to those with lower limb tumors (OR = 2.38, 95% CI: 1.51, 3.69). A similar observation was seen in dogs with trunk tumors compared to dogs with forelimb tumors (OR = 3.28, 95% CI 1.36, 7.50). Other associations were observed in humans but not in dogs. Humans aged 20-29 years had lower odds of metastasis at diagnosis compared to those aged 10-14 years (OR = 0.67, 95% CI: 0.47, 0.96); every 1-cm increase in tumor size was associated with a 6% increase in the odds of metastasis at diagnosis (95% CI: 1.04, 1.08); compared to those with a white, non-Hispanic race, higher odds were observed among those with a black, non-Hispanic race (OR: 1.51, 95% CI: 1.04, 2.16), and those with a Hispanic origin (OR 1.35, 95% CI: 1.00, 1.81). CONCLUSION: A common mechanism may be driving trunk tumors to progress to detectable metastasis prior to diagnosis in both species.

Feline large-cell lymphoma following previous treatment for small-cell gastrointestinal lymphoma: incidence, clinical signs, clinicopathologic data, treatment of a secondary malignancy, response and survival.

OBJECTIVES: Lymphoma is a common and clinically important malignancy in cats. Development of a second malignancy has been reported previously in 7-14% of cats with small-cell gastrointestinal (GI) lymphoma. The aim of our study was to describe the incidence, clinical signs, clinicopathologic data, response to therapy and outcomes in cats diagnosed with large-cell lymphoma following treatment for small-cell GI lymphoma. METHODS: Medical records from a single referral specialty hospital were reviewed for all cats with lymphoma diagnosed between 2008 and 2017. The cases with a diagnosis of small-cell GI lymphoma followed by a diagnosis of any large-cell lymphoma and complete outcome data were selected for further review. RESULTS: Seven hundred and forty cats with a diagnosis of lymphoma were identified. Twelve cats (12/121) treated for small-cell GI lymphoma followed by a diagnosis of any anatomic form of large cell lymphoma were identified. Nine cats met the study inclusion criteria and were used in analyses. Mean event-free survival time from small-cell GI lymphoma diagnosis until diagnosis of large-cell lymphoma was 543 days, with a median survival time of 615 days. Mean event-free survival time from large-cell lymphoma to death was 55 days, with a median survival time of 24.5 days. Hematocrit, albumin and total protein were significantly decreased when cats developed large-cell lymphoma compared with their values at the time of small-cell lymphoma diagnosis. CONCLUSIONS AND RELEVANCE: Large-cell lymphoma occurred in 9.9% (12/121) of cats treated for small-cell GI lymphoma. Feline practitioners should include large-cell lymphoma on their list of differential diagnoses in cats diagnosed with small-cell GI lymphoma developing weight loss, anemia, hypoalbuminemia and hypoproteinemia.

Effect of cross-match on packed cell volume after transfusion of packed red blood cells in transfusion-naïve anemic cats.

BACKGROUND: Novel feline RBC antigens might contribute to decreased efficacy of RBC transfusion and increased incidence of acute transfusion reactions (ATR). OBJECTIVES: To examine the effect of major cross-match in transfusion-naïve anemic cats on the incidence of acute immunologic transfusion reaction and transfusion efficacy for up to 24 hours after transfusion. ANIMALS: Forty-eight client owned transfusion-naïve anemic cats. METHODS: Prospective, randomized, controlled study. All transfusion-naïve cats receiving packed red blood cells (pRBC) transfusions from January 2016 to August 2017 were eligible for inclusion. Cats in the study group received cross-match and blood type compatible pRBCs and cats in the control group received noncross-matched blood type compatible pRBCs. Incidence of ATR and change in PCV after transfusion was recorded. RESULTS: No significant difference in incidence of transfusion reactions between cross-matched and noncross-matched groups (CM+ 4/24; 17%, CM- 7/24; 29%, P = .16). No significant difference between groups in mean change in PCV after transfusion scaled to dose of pRBCs administered at any time point after transfusion (immediate: CM+ 0.62 ± 0.59, CM- 0.75 ± 0.48, P = .41; 1 hour: CM+ 0.60 ± 0.66, CM- 0.74 ± 0.53, P = .43; 12 hours: CM+ 0.70 ± 0.55, CM- 0.66 ± 0.60, P = .81; 24 hours: CM+ 0.64 ± 0.71, CM- 0.55 ± 0.48, P = .70). CONCLUSIONS AND CLINICAL IMPORTANCE: Our results do not support use of the major cross-match test to increase efficacy of, and to decrease adverse events associated with, RBC transfusion in AB blood typed transfusion-naïve cats.

Retrospective evaluation of toceranib phosphate (Palladia) in cats with oral squamous cell carcinoma.

Objectives The aim of the study was to determine the clinical benefit and adverse event profile of toceranib phosphate in the treatment of feline oral squamous cell carcinoma (FOSCC). Methods Data obtained from the medical records of cats with oral squamous cell carcinoma diagnosed between 2010 and 2014 treated with toceranib phosphate were compared with medical record data from cats that did not receive toceranib, cytotoxic chemotherapy or radiation, to determine the response to toceranib treatment and adverse event profile of toceranib in cats. Concurrent use of non-steroidal anti-inflammatory drugs (NSAIDs) was allowed. Results Forty-six cats with FOSCC were included; 23 received treatment with toceranib (group 1) and 23 did not (group 2). The overall biological response rate in group 1 was 56.5%. Median survival time of toceranib-treated cats was significantly longer at 123 days compared with 45 days in cats not treated with toceranib ( P = 0.01). Cats achieving stable disease or better on toceranib therapy had significantly longer progression-free survival ( P <0.0001) and median survival ( P = 0.0042) times than those with progressive disease on toceranib. Administration of NSAIDs was also associated with significantly improved survival time ( P = 0.0038) among all cats. Anorexia was common but may reflect the underlying disease in these patients. Toceranib was well tolerated in cats, with the most common side effect being mild gastrointestinal toxicity. Conclusions and relevance Toceranib was well tolerated in cats with oral squamous cell carcinoma and may lead to improved survival times, especially when combined with NSAIDs. NSAID administration was also associated with improved survival times, and the relative benefit of toceranib and NSAIDs is difficult to determine from this retrospective study. Despite improvement in survival times, long-term survival in this patient population remained poor. As toceranib was well tolerated and may improve survival time, prospective evaluation of toceranib alone is warranted to assess response as a single agent and as part of multimodal therapy in an effort to achieve a more durable response in FOSCC.

Canine Cutaneous and Subcutaneous Soft Tissue Sarcoma: An Evidence-Based Review of Case Management.

Canine cutaneous and subcutaneous soft tissue sarcomas (STS) account for 20.3% of malignant neoplasms of the skin. This article makes recommendations for the diagnosis, treatment, and follow-up in dogs with STS, using evidence-based medicine concepts. Although our review of the literature on the management of canine STS found many of the studies to be less than rigorous, board-certified specialists in internal medicine, surgery, pathology, oncology, and radiation oncology were able to make several recommendations based on the literature review: cytology and biopsy are important for presurgical planning; wide (>3 cm margins) surgical excision decreases the likelihood of tumor recurrence; the use of a histologic grading scale is useful in predicting biologic behavior; and, in select cases, chemotherapy and radiation therapy may be beneficial adjunct treatments to surgical excision. More research is necessary to determine minimum size of surgical margins, the impact of radiation therapy on incompletely resected tumors, the ideal chemotherapy protocol for high grade STS, and the optimal methods of monitoring dogs for tumor recurrence and metastasis.

Evaluation of the relationship between clinical variables and thromboelastographic findings in dogs with protein-losing nephropathy.

OBJECTIVE: To determine whether hypercoagulability in proteinuric dogs, defined by thromboelastography (TEG), is related to the degree of proteinuria, presence of systemic arterial hypertension, presence of hypoalbuminemia, or reduced antithrombin activity. DESIGN: Prospective study of client-owned dogs. Data collected from each patient included signalment, body weight, urine protein-to-creatinine ratio (UPC), serum albumin concentration, TEG values, noninvasive arterial blood pressure, and AT activity. Hypercoagulability was diagnosed by TEG and odds ratios for other measurements were assessed by univariate logistic regression. SETTING: Urban referral center and teaching hospital. ANIMALS: Seventy-six dogs with protein-losing nephropathy (PLN) based on UPC, diagnosed between Oct 2009 and Oct 2012. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: The prevalence of hypercoagulability was 89%. No statistically significant associations were detected between hypercoagulability and UPC, serum albumin, noninvasive blood pressure, or AT activity (all P > 0.05). The prevalence of thromboembolism was 6.6%. CONCLUSIONS: Hypercoagulability was prevalent in dogs with PLN but could not be predicted based upon the presence or degree of proteinuria, systemic arterial hypertension, hypoalbuminemia, or low AT activity. The prevalance of thromboembolism was low in this population with PLN.

Cutaneous MCTs: associations with spay/neuter status, breed, body size, and phylogenetic cluster.

Certain breeds are known to be overrepresented among mast cell tumor (MCT) patients, but other risk factors have not been evaluated. This study presents results from a case-control study of 252 dogs with grade 2 or grade 3 cutaneous MCT. Increased risk for MCT development was found in spayed females (adjusted odds ratio [OR], 4.11), boxers (adjusted OR, 6.09), Labrador retrievers (adjusted OR, 3.95), pugs (adjusted OR, 3.17), golden retrievers (adjusted OR, 2.12), the mastiff and terrier phylogenetic cluster (adjusted OR, 3.19), and breeds classified as large (adjusted OR, 2.10) or giant (adjusted OR, 5.44). Additional studies are needed to evaluate the role of these and other potential risk factors in MCT development.

Feline exocrine pancreatic insufficiency: 16 cases (1992-2007).

Medical records of 16 cats diagnosed with exocrine pancreatic insufficiency (EPI) were reviewed. The diagnosis was confirmed with either a serum feline trypsin-like immunoreactivity (fTLI) concentration

Influence of carboplatin infusion on osteosarcoma blood flow.

PURPOSE: Herein we report that carboplatin infusion influenced tumor blood flow signal independent of the mechanical decompression induced by the artificial lymphatics system technology that was being evaluated as part of a randomized veterinary clinical trial, treating spontaneously occurring canine appendicular osteosarcoma, a tumor very similar to its human counterpart. METHODS: Blood flow within the central region of the tumor was recorded continuously using laser Doppler flowmetry, a real-time measurement technology. Time-averaged flow values were computed from segments taken from the recordings immediately before starting carboplatin infusion, and during infusion. RESULTS: Carboplatin increased the tumor blood flow signal by an additional 59 +/- 26% (mean +/- SEM; p = 0.06) over the increase induced by the decompression. The increase started within 49 +/- 46 s after the start of infusion, had a response time constant of 19 +/- 21 s and persisted throughout the infusion, ending shortly after infusion ended. CONCLUSION: The rapidity of the flow signal increase suggests that carboplatin may have an autonomic effect on circulation, either local or systemic. The observations identify a new action of this drug and suggest a possible mechanism to exploit therapeutically.

Use of an artificial lymphatic system during carboplatin infusion to improve canine osteosarcoma blood flow and clinical response.

BACKGROUND: The artificial lymphatic system (ALS), a mechanical system designed to reduce increased interstitial fluid pressure in solid tumors and enhance the delivery of chemotherapy, was evaluated within a randomized clinical trial treating spontaneously occurring canine appendicular osteosarcoma (OS), a tumor similar to its human OS counterpart. METHODS: An ALS was investigated for its ability to increase OS blood flow and increase uptake of intravenously administered carboplatin. RESULTS: Blood flow increased by 314% in tumors with active ALS drains versus 126% in control tumors (P < .03). Tumor carboplatin uptake increased by 51% after drain activation (P = .07). Microvascular density (MVD) was measured in tumors after surgical amputation and in corresponding bone regions in a cohort of normal dogs. The OS tumors had equivalent MVD as normal bone, and MVD was higher in the humerus than the femur (P < .03) in both tumor and normal bone. Median survival between the ALS-treated and control cohorts was not different despite increased drug uptake or ALS manipulation. Compared with historic controls, ALS drain insertion into tumors to reduce interstitial fluid pressure did not worsen the prognosis. CONCLUSIONS: The findings in canine spontaneously occurring OS indicate that an ALS may be of value as a chemotherapy adjunct for enhancing the delivery of chemotherapy to tumor interstitium.

Red blood cell transfusions in cats: 126 cases (1999).

OBJECTIVE: To determine the number of and reasons for RBC transfusions, incidence of acute transfusion reactions, prevalence of blood types, volume of blood administered, change in PCV, and clinical outcome in cats. DESIGN: Retrospective study. ANIMALS: 126 cats that received RBC transfusions. PROCEDURE: Medical records of cats that received whole blood or packed RBC transfusions were reviewed for signalment, blood type, pre- and post-transfusion PCV, volume of blood product administered, clinical diagnosis and cause of anemia, clinical signs of acute transfusion reactions, and clinical outcome. RESULTS: Mean volume of whole blood administered i.v. was 172 mL/kg (7.8 mL/lb) versus 9.3 mL/kg (4.2 mL/lb) for packed RBCs. Ninety-four percent of cats had blood type A. Mean increase in PCV among all cats was 6%. Fifty-two percent of cats had anemia attributed to blood loss, 10% had anemia attributed to hemolysis, and 38% had anemia attributed to erythropoietic failure. Acute transfusion reactions occurred in 11 cats. Sixty percent of cats survived until discharge. CONCLUSIONS AND CLINICAL RELEVANCE: RBC transfusions resulted in an increase in PCV in cats with all causes of anemia in this study. The rate of death was greater than in cats that did not receive transfusions, but seriousness of the underlying disease in the 2 groups may not be comparable. Death rate of cats that received transfusions was not attributable to a high rate of transfusion reactions. Results confirm that pretransfusion blood typing or crossmatching is required to minimize the risk of adverse reactions.

Canine and feline blood donor screening for infectious disease.

Thousands of blood transfusions are performed each year on dogs and cats, and the demand for blood products continues to grow. Risks associated with transfusions include the risk of disease transmission. Appropriate screening of blood donors for bloodborne infectious disease agents should be performed to lessen this risk. Geographic restrictions of disease, breed predilection, and documentation of actual disease transmission by transfusion all are factors that might need to be considered when making a decision on what screening program to use. In addition, factors involving general health care and management of blood donors should be employed to further ensure blood safety.