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.

Accelerating wheat breeding for end-use quality through association mapping and multivariate genomic prediction.

In hard-winter wheat (Triticum aestivum L.) breeding, the evaluation of end-use quality is expensive and time-consuming, being relegated to the final stages of the breeding program after selection for many traits including disease resistance, agronomic performance, and grain yield. In this study, our objectives were to identify genetic variants underlying baking quality traits through genome-wide association study (GWAS) and develop improved genomic selection (GS) models for the quality traits in hard-winter wheat. Advanced breeding lines (n = 462) from 2015-2017 were genotyped using genotyping-by-sequencing (GBS) and evaluated for baking quality. Significant associations were detected for mixograph mixing time and bake mixing time, most of which were within or in tight linkage to glutenin and gliadin loci and could be suitable for marker-assisted breeding. Candidate genes for newly associated loci are phosphate-dependent decarboxylase and lipid transfer protein genes, which are believed to affect nitrogen metabolism and dough development, respectively. The use of GS can both shorten the breeding cycle time and significantly increase the number of lines that could be selected for quality traits, thus we evaluated various GS models for end-use quality traits. As a baseline, univariate GS models had 0.25-0.55 prediction accuracy in cross-validation and from 0 to 0.41 in forward prediction. By including secondary traits as additional predictor variables (univariate GS with covariates) or correlated response variables (multivariate GS), the prediction accuracies were increased relative to the univariate model using only genomic information. The improved genomic prediction models have great potential to further accelerate wheat breeding for end-use quality.

Effect of Tempering Conditions on White Sorghum Milling, Flour, and Bread Properties.

The effects of room temperature water, hot water, and steam tempering methods were investigated on sorghum kernel physical properties, milling, flour, and bread-making properties. Overall tempering condition and tempering moisture content were found to have a significant effect on the physical properties. Milling properties were evaluated using a laboratory-scale roller milling flowsheet consisting of four break rolls and eight reduction rolls. Room temperature tempering (18% moisture for 24 h) led to better separation of bran and endosperm without negatively impacting flour quality characteristics i.e., particle size distribution, flour yield, protein, ash, damaged starch, and moisture content. Bread produced from the flour obtained from milling sorghum kernels tempered with room temperature water (18% m.c for 24 h) and hot water (16% m.c at 60 °C for 18 h) displayed better bread-making properties i.e., high firmness, resilience, volume index, higher number of cells, and thinner cell walls when compared to other tempering conditions. Room temperature water tempering treatment (18% m.c for 24 h) could be a better pretreatment process for milling white sorghum kernels without negatively impacting the flour and bread-making quality characteristics.

Survival time for dogs with previously untreated, peripheral nodal, intermediate- or large-cell lymphoma treated with prednisone alone: the Canine Lymphoma Steroid Only trial.

OBJECTIVE: To evaluate survival times for dogs with previously untreated, peripheral nodal, intermediate- or large-cell lymphoma treated with prednisone alone. ANIMALS: 109 client-owned dogs recruited from 15 institutions in the United States. PROCEDURES: Dogs were treated with prednisone at a dosage of 40 mg/m2, PO, once daily for 7 days and at a dosage of 20 mg/m2, PO, once daily thereafter. Quality of life (QOL) was assessed by owners with a visual analog scale when treatment was started (day 0), 1 and 2 weeks after treatment was started, and every 4 weeks thereafter. The primary outcome of interest was survival time as determined by the Kaplan-Meier method. Factors potentially associated with survival time were examined. RESULTS: Median overall survival time was 50 days (95% CI, 41 to 59 days). Factors associated with survival time included substage (a vs b) and immunophenotype (B cell vs T cell). Owner-assigned QOL scores on days 0 and 14 were significantly positively correlated with survival time. When QOL score was dichotomized, dogs with day 0 or day 14 QOL scores ≥ 50 had significantly longer survival times, compared with dogs with day 0 or day 14 QOL scores < 50. No variables were predictive of long-term (> 120 days) survival. CONCLUSIONS AND CLINICAL RELEVANCE: Results suggested that survival times were short for dogs with previously untreated, peripheral nodal, intermediate- or large-cell lymphoma treated with prednisone alone. Owner-perceived QOL and clinician-assigned substage were both associated with survival time. Findings provide potentially important information for clinicians to discuss with owners of dogs with lymphoma at the time treatment decisions are made.

Suspected Carboplatin Extravasation Reactions in Seven Dogs.

Carboplatin is a platinum chemotherapeutic agent commonly used in veterinary oncology that is currently classified as an irritant to local tissues when extravasated. To the authors' knowledge, there are no reports of vesicant injuries associated with carboplatin administration reported in the veterinary literature. In this case series, seven dogs are described to have experienced injuries following a suspected carboplatin extravasation resembling vesicant injuries a median of 7 days after carboplatin administration (range 4-15 days). Wounds healed with a variety of treatments, including medical management and/or surgical debridement, a median of 25.5 days (range 7-49 days) after observation of the suspected extravasation injury. There were no obvious similarities involving carboplatin administration among patients to explain why these reactions occurred. Extravasation injury should be considered a possible local complication associated with carboplatin chemotherapy.

Post-surgical outcome and prognostic factors in canine malignant melanomas of the haired skin: 87 cases (2003-2015).

The medical records of 87 dogs treated with surgery for cutaneous malignant melanoma (CMM) of the haired skin were retrospectively reviewed for overall survival time (OST), progression-free survival time (PFS), and prognostic factors. The post-surgery median PFS and median OST were 1282 days and 1363 days, respectively. The post-surgery metastatic rate was 21.8% with a local recurrence rate of 8%. Increasing mitotic index (MI) was predictive of a significantly decreased OST and PFS on multivariable analysis [hazard ratio (HR): 1.05, 95% confidence interval (CI): 1.02 to 1.07 and HR: 1.04, 95% CI: 1.02 to 1.06, respectively]. Increasing age was likewise predictive of a significantly decreased OST and PFS on multivariable analysis (HR: 1.39, 95% CI: 1.17 to 1.65 and HR: 1.33, 95% CI: 1.14 to 1.54, respectively). These results confirm clinical impressions that long survival times are likely in dogs diagnosed with malignant melanoma of the haired skin when treated with surgery alone.

Résultat post-chirurgical et facteurs de pronostic pour les mélanomes malins canins de la peau poilue : 87 cas (2003­2015). Les dossiers médicaux de 87 chiens traités à l'aide d'une chirurgie pour le mélanome malin cutané (MMC) de la peau poilue ont été évalués rétrospectivement pour le temps de survie global (TSG), le temps de survie sans progression (TSSP) et les facteurs de pronostic. Le TSSP médian après la chirurgie et le TSG médian étaient de 1282 jours et de 1363 jours, respectivement. Le taux métastasique après la chirurgie était de 21,8 % avec un taux de récurrence local de 8 %. L'augmentation de l'indice mitotique (IM) était prédictive d'un TSG et d'un TSSP réduits à l'analyse multivariable (ratio de risque [RR] : 1,05, intervalle de confiance [IC] de 95 % : 1,02 à 1,07 et RR : 1,04, IC de 95 % : 1,02 à 1,06, respectivement). La progression de l'âge était aussi prédictive d'une réduction importante du TSG et du TSSP à l'analyse multivariable (RR : 1,39, IC de 95 % : 1,17 à 1,65 et RR : 1,33, IC de 95 % : 1,14 à 1,54, respectivement). Ces résultats confirment les impressions cliniques que des longs délais de survie sont probables chez les chiens diagnostiqués avec le mélanome malin de la peau poilue lorsqu'ils sont uniquement traités à l'aide d'une chirurgie.(Traduit par Isabelle Vallières).

Cytotoxic effects of loperamide hydrochloride on canine cancer cells.

Loperamide is a peripheral opiate agonist that can cause apoptosis and G2/M arrest in human cancer cell lines and may sensitize cells to chemotherapy. The objectives of this study were to investigate the effects of loperamide on viability, apoptosis and cell cycle kinetics in canine cancer cells and to establish whether the drug sensitizes cells to doxorubicin. Cell viability was assessed using Alamar Blue. Cell death and cell cycle were studied using flow cytometry with 7-Aminoactinomycin-D (7-AAD) and propidium iodide (PI), respectively. Loperamide decreased cell viability in a dose-dependent fashion and was most effective against canine osteosarcoma cells. In all cell lines, it induced a dose and time dependent apoptosis and resulted in accumulation in G0/G1. When co-incubated with doxorubicin, loperamide induced a synergistic cell kill in canine carcinoma cells. Investigation is warranted into the role of loperamide in the treatment of canine cancer.