SGLT2 inhibitor use in the management of feline diabetes mellitus.

Sodium-glucose cotransporter-2 (SGLT2) inhibitors are routinely used in the management of human type 2 diabetes and have been shown to effectively mitigate hyperglycemia and reduce the risks of cardiovascular and renal compromise. Two SGLT2 inhibitors, namely bexagliflozin and velagliflozin, were recently FDA approved for the treatment of uncomplicated feline diabetes mellitus. These oral hypoglycemic agents are a suitable option for many newly diagnosed cats, with rapid improvements in glycemic control and clinical signs. Suitable candidates must have some residual ß-cell function, as some endogenous insulin production is required to prevent ketosis. Appropriate patient selection and monitoring are necessary, and practitioners should be aware of serious complications such as euglycemic diabetic ketoacidosis.

Dysphagia-optimised intensity-modulated radiotherapy versus standard intensity-modulated radiotherapy in patients with head and neck cancer (DARS): a phase 3, multicentre, randomised, controlled trial.

BACKGROUND: Most newly diagnosed oropharyngeal and hypopharyngeal cancers are treated with chemoradiotherapy with curative intent but at the consequence of adverse effects on quality of life. We aimed to investigate if dysphagia-optimised intensity-modulated radiotherapy (DO-IMRT) reduced radiation dose to the dysphagia and aspiration related structures and improved swallowing function compared with standard IMRT. METHODS: DARS was a parallel-group, phase 3, multicentre, randomised, controlled trial done in 22 radiotherapy centres in Ireland and the UK. Participants were aged 18 years and older, had T1-4, N0-3, M0 oropharyngeal or hypopharyngeal cancer, a WHO performance status of 0 or 1, and no pre-existing swallowing dysfunction. Participants were centrally randomly assigned (1:1) using a minimisation algorithm (balancing factors: centre, chemotherapy use, tumour type, American Joint Committee on Cancer tumour stage) to receive DO-IMRT or standard IMRT. Participants and speech language therapists were masked to treatment allocation. Radiotherapy was given in 30 fractions over 6 weeks. Dose was 65 Gy to primary and nodal tumour and 54 Gy to remaining pharyngeal subsite and nodal areas at risk of microscopic disease. For DO-IMRT, the volume of the superior and middle pharyngeal constrictor muscle or inferior pharyngeal constrictor muscle lying outside the high-dose target volume had a mandatory 50 Gy mean dose constraint. The primary endpoint was MD Anderson Dysphagia Inventory (MDADI) composite score 12 months after radiotherapy, analysed in the modified intention-to-treat population that included only patients who completed a 12-month assessment; safety was assessed in all randomly assigned patients who received at least one fraction of radiotherapy. The study is registered with the ISRCTN registry, ISRCTN25458988, and is complete. FINDINGS: From June 24, 2016, to April 27, 2018, 118 patients were registered, 112 of whom were randomly assigned (56 to each treatment group). 22 (20%) participants were female and 90 (80%) were male; median age was 57 years (IQR 52-62). Median follow-up was 39·5 months (IQR 37·8-50·0). Patients in the DO-IMRT group had significantly higher MDADI composite scores at 12 months than patients in the standard IMRT group (mean score 77·7 [SD 16·1] vs 70·6 [17·3]; mean difference 7·2 [95% CI 0·4-13·9]; p=0·037). 25 serious adverse events (16 serious adverse events assessed as unrelated to study treatment [nine in the DO-IMRT group and seven in the standard IMRT group] and nine serious adverse reactions [two vs seven]) were reported in 23 patients. The most common grade 3-4 late adverse events were hearing impairment (nine [16%] of 55 in the DO-IMRT group vs seven [13%] of 55 in the standard IMRT group), dry mouth (three [5%] vs eight [15%]), and dysphagia (three [5%] vs eight [15%]). There were no treatment-related deaths. INTERPRETATION: Our findings suggest that DO-IMRT improves patient-reported swallowing function compared with standard IMRT. DO-IMRT should be considered a new standard of care for patients receiving radiotherapy for pharyngeal cancers. FUNDING: Cancer Research UK.

Replacing a Veterinary Physiology Endocrinology Lecture with a Blended Learning Approach Using an Everyday Analogy.

Understanding scientific concepts and processes is critical for veterinary education. This article outlines the impact of blended learning and the use of an analogy on student understanding of the hypothalamic-pituitary-target gland axis over a three-year period. The first-year veterinary physiology course at our institution was modified to incorporate a blended learning approach. An analogy centered around a fast-food restaurant was introduced via an animated video to explain key concepts using an online module. Students completed the module on their own time and class time was optional for asking questions or obtaining clarification as needed. Learning was assessed using the same set of multiple-choice exam questions (MCQs). As hypothesized, students using the online module performed equally well (significantly better for those in the lower quartile) on three summative MCQs to those who received the same information delivered by traditional lecture. Student feedback identified positive aspects regarding blended learning using the analogy, including dynamic visuals, ability to work at their own time and pace, and ease of repeating information. Students cited lack of discipline and poor time management as obstacles to completing the module. Changing the anatomy and physiology of the hypothalamus and pituitary gland from static images and text to an animated video significantly improved student's preference for the blended learning approach. Blended learning and the analogy was preferred by 47% of students over the traditional lecture format (21% preferred traditional lecture and 32% were indifferent) and it was more effective in helping students master this important physiological concept.

Mucocutaneous nasal histoplasmosis in an immunocompetent dog.

BACKGROUND: Histoplasma (H.) capsulatum is a dimorphic fungus, and infection is typically via inhalation of microconidia. After conversion to the yeast phase within the lung, the organism is subsequently disseminated to other tissues by macrophages. Nasal histoplasmosis appears to be a rare condition in dogs. CASE PRESENTATION: We report the clinical case of a 4.5-year-old male neutered Cocker spaniel/Poodle mix, 7.7 kg, body condition score 6/9, that presented with a 3-month history of sneezing and left-sided mucoid nasal discharge. The history also included a mild swelling (transient) of the right carpus with a lameness (grade II-III/IV), coinciding with the onset of sneezing and nasal discharge. The dog lived primarily indoors in the Texas Gulf Coast area. On physical examination, the dog was febrile, and the left nostril was swollen, ulcerative, deformed, and hypopigmented. Mandibular lymph nodes were firm and mildly enlarged bilaterally. Mild lymphopenia, thrombocytopenia, and hyperglobulinemia were noted. Thoracic radiographs were unremarkable. Computed tomography and rhinoscopy revealed swelling of the rostral portion of the left and right nasal passages. Cytology and histology of biopsies of the affected nasal tissue showed pyogranulomatous inflammation and yeast organisms consistent with H. capsulatum. Weak antigenuria was detected on the MVista H. capsulatum antigen test. Treatment with oral itraconazole led to a resolution of the nasal signs and normalization of the appearance of the nostril over 13 weeks, and neither antigenuria nor antigenemia was detected on several recheck examinations. The dog remained in good general and physical condition and showed no signs of disease recurrence more than 6 years after the last examination. CONCLUSION: We report a rare case of nasal mucocutaneous histoplasmosis in an immunocompetent dog, with an excellent clinical response to oral itraconazole. This case documents that histoplasmosis in dogs can affect primarily the nasal cavity, which responds rapidly to triazole antifungal therapy and has a good prognosis. A similar case has only been reported in human medicine in a young adult.

Small Animal Resident Selection Processes at a University Teaching Hospital: An Analysis and Recommendations for Improvement.

Concerns regarding resident performance within a small animal department prompted a review of selection practices, with the intent of improving validity and efficiency. Information was gathered from semi-structured interviews and descriptions of current processes; emphasis was placed on determining how the Veterinary Internship and Residency Matching Program application was used. Processes were found to lack standardization and rely heavily on arbitrary judgments. In addition, faculty members expressed concerns regarding their reliability and the time spent generating candidate rankings. Suggestions for improvement were based on current practices in personnel psychology and human resource management. The need for standardization within and across specialty groups was emphasized, along with a multiple-hurdle approach in which a substantial deficit or red flag in any component results in candidate disqualification. Comprehensive recommendations were made for the selection process as follows: Each application undergoes initial administrative screening for employment eligibility and academic cut-offs; eligible applications are scored by 2-3 faculty members using defined ratings on four equally weighted pre-interview criteria (i.e., veterinary education, post-graduation experiences, personal statement, and standardized letters of reference); phone calls to colleagues with knowledge of the applicant follow specific guidelines and a rating scale; veterinary-situational structured interview questions with appropriate rating scales are used to assess candidates' standing on specified competencies identified as important for success; and the interview score is weighted equally and added to the four pre-interview components to determine the final rank. It is hoped this new approach will take less time and facilitate the selection of successful residents.

Radiotherapy plus cisplatin or cetuximab in low-risk human papillomavirus-positive oropharyngeal cancer (De-ESCALaTE HPV): an open-label randomised controlled phase 3 trial.

BACKGROUND: The incidence of human papillomavirus (HPV)-positive oropharyngeal cancer, a disease affecting younger patients, is rapidly increasing. Cetuximab, an epidermal growth factor receptor inhibitor, has been proposed for treatment de-escalation in this setting to reduce the toxicity of standard cisplatin treatment, but no randomised evidence exists for the efficacy of this strategy. METHODS: We did an open-label randomised controlled phase 3 trial at 32 head and neck treatment centres in Ireland, the Netherlands, and the UK, in patients aged 18 years or older with HPV-positive low-risk oropharyngeal cancer (non-smokers or lifetime smokers with a smoking history of <10 pack-years). Eligible patients were randomly assigned (1:1) to receive, in addition to radiotherapy (70 Gy in 35 fractions), either intravenous cisplatin (100 mg/m2 on days 1, 22, and 43 of radiotherapy) or intravenous cetuximab (400 mg/m2 loading dose followed by seven weekly infusions of 250 mg/m2). The primary outcome was overall severe (grade 3-5) toxicity events at 24 months from the end of treatment. The primary outcome was assessed by intention-to-treat and per-protocol analyses. This trial is registered with the ISRCTN registry, number ISRCTN33522080. FINDINGS: Between Nov 12, 2012, and Oct 1, 2016, 334 patients were recruited (166 in the cisplatin group and 168 in the cetuximab group). Overall (acute and late) severe (grade 3-5) toxicity did not differ significantly between treatment groups at 24 months (mean number of events per patient 4·8 [95% CI 4·2-5·4] with cisplatin vs 4·8 [4·2-5·4] with cetuximab; p=0·98). At 24 months, overall all-grade toxicity did not differ significantly either (mean number of events per patient 29·2 [95% CI 27·3-31·0] with cisplatin vs 30·1 [28·3-31·9] with cetuximab; p=0·49). However, there was a significant difference between cisplatin and cetuximab in 2-year overall survival (97·5% vs 89·4%, hazard ratio 5·0 [95% CI 1·7-14·7]; p=0·001) and 2-year recurrence (6·0% vs 16·1%, 3·4 [1·6-7·2]; p=0·0007). INTERPRETATION: Compared with the standard cisplatin regimen, cetuximab showed no benefit in terms of reduced toxicity, but instead showed significant detriment in terms of tumour control. Cisplatin and radiotherapy should be used as the standard of care for HPV-positive low-risk patients who are able to tolerate cisplatin. FUNDING: Cancer Research UK.

Bacterial Biogeography of the Colon in Dogs With Chronic Inflammatory Enteropathy.

The intestinal microbiota is believed to play a role in the pathogenesis of inflammatory bowel disease in humans and chronic inflammatory enteropathy (CIE) in dogs. While most previous studies have described the gut microbiota using sequencing methods, it is fundamental to assess the spatial distribution of the bacteria for a better understanding of their relationship with the host. The microbiota in the colonic mucosa of 22 dogs with CIE and 11 control dogs was investigated using fluorescence in situ hybridization (FISH) with a universal eubacterial probe (EUB338) and specific probes for select bacterial groups. The number of total bacteria labeled with EUB338 probe was lower within the colonic crypts of dogs with CIE compared to controls. Helicobacter spp. and Akkermansia spp. were decreased on the colonic surface and in the crypts of dogs with CIE. Dogs with CIE had increased number of Escherichia coli/Shigella spp. on the colonic surface and within the crypts compared to control dogs. In conclusion, the bacterial microbiota in the colonic mucosa differed between dogs with and without CIE, with depletion of the crypt bacteria in dogs with CIE. The crypt bacterial species that was intimately associated with the host mucosa in control dogs was composed mainly of Helicobacter spp.

Clinical pharmacokinetics and outcomes of oral fluconazole therapy in dogs and cats with naturally occurring fungal disease.

This multi-institutional study was designed to determine the clinical pharmacokinetics of fluconazole and outcomes in client-owned dogs (n = 37) and cats (n = 35) with fungal disease. Fluconazole serum concentrations were measured. Pharmacokinetic analysis was limited to animals at steady state (≥72 hr of treatment). The mean (range) body weight in 31 dogs was 25.6 (2.8-58.2) kg and in 31 cats was 3.9 (2.4-6.1) kg included in pharmacokinetic analyses. The dose, average steady-state serum concentrations (CSS ), and oral clearance in dogs were 14.2 (4.5-21.3) mg/kg/d, 26.8 (3.8-61.5) µg/mL, and 0.63 ml min-1  kg-1 , respectively, and in cats were 18.6 (8.2-40.0) mg/kg/d, 32.1 (1.9-103.5) µg/mL, and 0.61 ml min-1  kg-1 , respectively. Random inter-animal pharmacokinetic variability was high in both species. Two dogs had near twofold increases in serum fluconazole when generic formulations were changed, suggesting lack of bioequivalence. Median CSS for dogs and cats achieving clinical remission was 19.4 and 35.8 µg/ml, respectively. Starting oral doses of 10 mg/kg q12h in dogs and 50-100 mg total daily dose in cats are recommended to achieve median CSS associated with clinical remission. Due to the large pharmacokinetic variability, individualized dose adjustments based on CSS (therapeutic drug monitoring) and treatment failure should be considered.

Sonographic findings of pinpoint hyperechoic foci in the small intestine, liver, and mesenteric lymph nodes are indicative of canine Heterobilharzia americana infection.

Canine schistosomiasis, caused by the trematode Heterobilharzia americana, can pose a diagnostic challenge due to nonspecific symptoms. The aim of this multicenter, retrospective, descriptive study was to compare the prevalence and extent of sonographic changes associated with schistosomiasis between affected and infection-free dogs. Medical records of two referral centers were searched for dogs with confirmed schistosomiasis that had undergone an abdominal ultrasound. Fifty-five cases fulfilled the inclusion criteria, and a contemporaneous control group was derived from dogs that tested negative for H. americana. Two blinded reviewers evaluated the images. The majority of Heterobilharzia-infected (further termed H-pos) dogs (82%) had ultrasonographic abnormalities in the small intestine ± liver. Abnormal layering of the small intestine was noted in 38 of 54 H-pos dogs, compared to six of 54 control dogs (P < .0001). Pinpoint hyperechoic foci were noted in the small intestinal submucosa or muscularis layers in 25 of 54 H-pos dogs, but only three controls (P < .0001). Heterogeneity of the hepatic parenchyma and pinpoint hyperechoic foci were more prevalent in H-pos dogs (65% vs 40%; P = .0213 and 44% vs 18%; P = .0068, respectively). Pinpoint hyperechoic foci within mesenteric lymph nodes were noted in seven H-pos dogs and none of the controls (P = .0128). The combination of heterogeneous small intestine wall layering and pinpoint hyperechoic foci in small intestine, liver, or mesenteric lymph nodes was the most reliable indication of infection (P = .0001; odds ratio = 36.87), with positive predictive value of 94%, yet modest sensitivity for the detection of infection (58%). Observing these sonographic features suggests schistosomiasis and should prompt further testing.

Multiple-Choice Questions in Small Animal Medicine: An Analysis of Cognitive Level and Structural Reliability, and the Impact of these Characteristics on Student Performance.

Students entering the final year of the veterinary curriculum need to integrate information and problem solve. Assessments used to document competency prior to entry to the clinical environment should ideally provide a reliable measurement of these essential skills. In this study, five internal medicine specialists evaluated the cognitive grade (CG) and structural integrity of 100 multiple-choice questions (MCQs) used to assess learning by third-year students at a United States (US) veterinary school. Questions in CG 1 tested factual recall and simple understanding; those in CG 2 required interpretation and analysis; CG 3 MCQs tested problem solving. The majority (53%) of questions could be answered correctly using only recall or simple understanding (CG 1); 12% of MCQs required problem solving (CG 3). Less than half of the questions (43%) were structurally sound. Overall student performance for the 3 CGs differed significantly (92% for CG 1 vs. 84% for CG 3; p = .03. Structural integrity did not appear to impact overall performance, with a median pass rate of 90% for flawless questions versus 86% for those with poor structural integrity (p = .314). There was a moderate positive correlation between individual student outcomes for flawless CG 1 versus CG 3 questions (rs = 0.471; p = < .001), although 13% of students failed to achieve an aggregate passing score (65%) on the CG 3 questions. These findings suggest that MCQ-based assessments may not adequately evaluate intended learning outcomes and that instructors may benefit from guidance and training for this issue.

Piecemeal endoscopic polypoidectomy for the management of a canine pharyngeal hemangiosarcoma.

A 7-year-old castrated male Maltese dog was presented for increased respiratory sounds, inability to bark, dysphagia, and hyporexia. Radiographs revealed an ovoid, opaque mass in the caudal nasopharynx. An airway examination and computed tomography scan were followed by endoscopic polypoidectomy. The mass was a hemangiosarcoma, and the patient survived > 13 months.

Polypoïdectomie endoscopique fragmentaire pour la gestion d'un hémangiosarcome pharyngé canin. Un chien Bichon maltais mâle castré âgé de 7 ans a été présenté pour des sons respiratoires accrus, l'incapacité de japper, de la dysphagie et de l'hyporexie. Les radiographies ont révélé une masse ovoïde opaque dans le nasopharynx caudal. Un examen des voies respiratoires et une tomodensitométrie ont été suivis d'une polypoïdectomie endoscopique. La masse était un hémangiosarcome et le patient a survécu >13 mois.(Traduit par Isabelle Vallières).

Addition of docetaxel, zoledronic acid, or both to first-line long-term hormone therapy in prostate cancer (STAMPEDE): survival results from an adaptive, multiarm, multistage, platform randomised controlled trial.

BACKGROUND: Long-term hormone therapy has been the standard of care for advanced prostate cancer since the 1940s. STAMPEDE is a randomised controlled trial using a multiarm, multistage platform design. It recruits men with high-risk, locally advanced, metastatic or recurrent prostate cancer who are starting first-line long-term hormone therapy. We report primary survival results for three research comparisons testing the addition of zoledronic acid, docetaxel, or their combination to standard of care versus standard of care alone. METHODS: Standard of care was hormone therapy for at least 2 years; radiotherapy was encouraged for men with N0M0 disease to November, 2011, then mandated; radiotherapy was optional for men with node-positive non-metastatic (N+M0) disease. Stratified randomisation (via minimisation) allocated men 2:1:1:1 to standard of care only (SOC-only; control), standard of care plus zoledronic acid (SOC + ZA), standard of care plus docetaxel (SOC + Doc), or standard of care with both zoledronic acid and docetaxel (SOC + ZA + Doc). Zoledronic acid (4 mg) was given for six 3-weekly cycles, then 4-weekly until 2 years, and docetaxel (75 mg/m(2)) for six 3-weekly cycles with prednisolone 10 mg daily. There was no blinding to treatment allocation. The primary outcome measure was overall survival. Pairwise comparisons of research versus control had 90% power at 2·5% one-sided α for hazard ratio (HR) 0·75, requiring roughly 400 control arm deaths. Statistical analyses were undertaken with standard log-rank-type methods for time-to-event data, with hazard ratios (HRs) and 95% CIs derived from adjusted Cox models. This trial is registered at ClinicalTrials.gov (NCT00268476) and ControlledTrials.com (ISRCTN78818544). FINDINGS: 2962 men were randomly assigned to four groups between Oct 5, 2005, and March 31, 2013. Median age was 65 years (IQR 60-71). 1817 (61%) men had M+ disease, 448 (15%) had N+/X M0, and 697 (24%) had N0M0. 165 (6%) men were previously treated with local therapy, and median prostate-specific antigen was 65 ng/mL (IQR 23-184). Median follow-up was 43 months (IQR 30-60). There were 415 deaths in the control group (347 [84%] prostate cancer). Median overall survival was 71 months (IQR 32 to not reached) for SOC-only, not reached (32 to not reached) for SOC + ZA (HR 0·94, 95% CI 0·79-1·11; p=0·450), 81 months (41 to not reached) for SOC + Doc (0·78, 0·66-0·93; p=0·006), and 76 months (39 to not reached) for SOC + ZA + Doc (0·82, 0·69-0·97; p=0·022). There was no evidence of heterogeneity in treatment effect (for any of the treatments) across prespecified subsets. Grade 3-5 adverse events were reported for 399 (32%) patients receiving SOC, 197 (32%) receiving SOC + ZA, 288 (52%) receiving SOC + Doc, and 269 (52%) receiving SOC + ZA + Doc. INTERPRETATION: Zoledronic acid showed no evidence of survival improvement and should not be part of standard of care for this population. Docetaxel chemotherapy, given at the time of long-term hormone therapy initiation, showed evidence of improved survival accompanied by an increase in adverse events. Docetaxel treatment should become part of standard of care for adequately fit men commencing long-term hormone therapy. FUNDING: Cancer Research UK, Medical Research Council, Novartis, Sanofi-Aventis, Pfizer, Janssen, Astellas, NIHR Clinical Research Network, Swiss Group for Clinical Cancer Research.

Prognostic value of C-reactive protein in dogs with elevated serum pancreatic lipase immunoreactivity concentrations.

OBJECTIVE: To determine the prognostic value of serum C-reactive protein (CRP) in dogs with pancreatitis. ANIMALS: 503 client-owned animals with pancreatic lipase immunoreactivity (PLI) > 600 µg/L. METHODS: Routine submissions to the Texas A&M Gastrointestinal Laboratory were monitored for canine samples with PLI > 600 µg/L. Clinics were emailed 2 weeks after PLI measurement and asked the following questions: (1) was the dog hospitalized, and (2) is the patient alive? If a response was received, serum CRP concentration was measured using leftover serum. RESULTS: Paired PLI and CRP results were available for 503 dogs. Median PLI was 984 µg/L (range, 603 to 2,001 µg/L); median CRP was 9.9 mg/L (range, 9.9 to 395.3 mg/L; ref: < 10 mg/L). Inpatient care was provided to 136 dogs (27.0%); 49 dogs (9.7%) died or were euthanized. Median PLI values for dogs that died versus survived were similar. Median CRP was higher in hospitalized dogs (36.1 vs 9.9 mg/L; P < .0001) and those that died (37.2 vs 9.9 mg/L; P < .0001). Compared to dogs with CRP < 10 mg/L, those with CRP > 10 mg/L were 5.3 times more likely to die (CI, 2.7 to 10.2) and 5.7 times (CI, 3.7 to 8.7) more likely to be hospitalized. CLINICAL RELEVANCE: In dogs with PLI > 600 µg/L, CRP > 10 mg/L was associated with increased risk of hospitalization or death. This biomarker may provide prognostic information in dogs with evidence of pancreatitis and guide decisions regarding hospitalization or referral.

Palatal erosion and oronasal fistulation following covered nasopharyngeal stent placement in two dogs.

Treatment options for dogs with nasopharyngeal stenosis include fluoroscopic placement of metallic stents. Reported complications include entrapment of hair and food, obstruction and persistent nasal discharge. Two toy breed dogs were examined for persistent nasal discharge and halitosis at 4 and 20 months after placement of permanent metallic stents for acquired nasopharyngeal stenosis. Full thickness defects were found in the palate of both dogs, with extensive communication between the mouth and the nasal passages. Portions of the metal stent were observed within the lesion in both patients. Additional treatment was declined by the owner of one dog; the stent was removed through the fistula in the other dog. Palatal erosion with secondary oronasal fistulation is a potential complication of nasopharyngeal stent placement in dogs.

Same-Day Surgery Clinic: A model for improving access to care at academic medical centers.

BACKGROUND: Best-practice models delivering surgical care in the preoperative setting are unknown. In April 2018, we established a Same-Day Clinic (SDC) to increase the access and efficiency of general surgical care delivery. METHODS: This is a single-institution retrospective cohort study. We included patients who underwent elective laparoscopic cholecystectomy, inguinal or umbilical hernia repair. 112 patients were seen in the year prior to clinic creation; 84 were seen in the year following clinic creation. RESULTS: After clinic creation, the percentage of patients referred following an emergency department encounter decreased from 33.4 to 17.9%. Patients referred from primary care encounters increased from 28.6 to 44%. Patients who underwent pre-referral imaging decreased from 58.9% to 44%. The SDC cohort was seen 11 days sooner (40 vs. 29d). CONCLUSION: The SDC increases access and decreases wait times to surgical treatment. It strengthens referral networks for traditionally underserved populations and reduces the burden of non-necessary preoperative imaging.

Effect of withholding food versus feeding on creatinine, symmetric dimethylarginine, cholesterol, triglycerides, and other biochemical analytes in 100 healthy dogs.

BACKGROUND: Withholding food is often recommended before collection of blood for routine biochemical analysis in dogs despite a paucity of evidence to support this requirement. OBJECTIVES: To compare measurements of selected biochemical analytes collected before and after feeding in clinically healthy dogs. ANIMALS: One hundred clinically healthy staff- and student-owned dogs weighing ≥15 kg. METHODS: Prospective observational study. Food was withheld from the dogs for 10-26 hours. Preprandial serum was collected, and then dogs were fed their usual food at an amount equivalent to at least 2/3 resting energy requirement (RER). Selected serum analytes were measured at 2-, 4-, 6-, and 8-hours postprandially. The proportion of postprandial values that exceeded either the reported allowable total error (TEa), or for symmetric dimethylarginine (SDMA), the reference change value (RCV), was determined. As neither TEa nor RCV is available for lipase, comparison was made to the high end of the reference interval (RI). RESULTS: The proportion of dogs with at least 1 postprandial measurement that exceeded the TEa or RCV was 92/100 for triglycerides, 66/100 for blood urea nitrogen (BUN), 46/100 for phosphorus, 17/100 for glucose, 9/100 for bilirubin, 5/100 for SDMA, 2/100 for creatinine, and 0/100 for cholesterol and albumin. Postprandial lipase never exceeded the RI in dogs with normal fasted lipase. CONCLUSIONS AND CLINICAL IMPORTANCE: Withholding food is generally not necessary before performing routine biochemical analysis in clinically healthy dogs. Withholding food might be helpful to limit variability in analytes impacted by feeding, such as triglycerides and phosphorus.

Clinical utility of fungal culture and antifungal susceptibility in cats and dogs with histoplasmosis.

BACKGROUND: Culture can be used for diagnosis and antifungal susceptibility testing in animals with fungal infections. Limited information is available regarding the diagnostic performance of culture and the susceptibility patterns of Histoplasma spp. isolates. HYPOTHESIS/OBJECTIVES: Describe the clinical utility of culture and the susceptibility patterns of Histoplasma spp. isolates causing histoplasmosis in cats and dogs. ANIMALS: Seventy-one client-owned animals, including 33 cats and 19 dogs with proven or probable histoplasmosis. METHODS: Culture was attempted from tissue or fluid samples. Diagnostic performance of culture, cytopathology, and antigen detection were compared with final diagnosis. Susceptibility to antifungal agents was determined for a subset (11 from dogs, 9 from cats) of culture isolates. RESULTS: Culture had a diagnostic sensitivity of 17/33 (52%; 95% confidence interval [CI], 34%-69%) and 15/19 (79%; 95% CI, 61%-97%) and specificity of 6/6 (100%; 95% CI, 54%-100%) and 10/10 (100%; 95% CI, 69%-100%) in cats and dogs, respectively. Culture was not positive in any animal in which cytopathology and antigen testing were negative. Target drug exposure (area under the concentration curve [AUC]/minimum inhibitory concentration [MIC] >25) should be easily achieved for all isolates for itraconazole, voriconazole, or posaconazole. Five of 20 (25%) isolates had fluconazole MIC ≥32 µg/mL and achieving target drug exposure is unlikely. CONCLUSIONS AND CLINICAL IMPORTANCE: Fungal culture did not improve diagnostic sensitivity when used with cytopathology and antigen detection. Susceptibility testing might help identify isolates for which fluconazole is less likely to be effective.

Clinical features of muscle stiffness in 37 dogs with concurrent naturally occurring hypercortisolism.

BACKGROUND: Severe muscle stiffness (SMS) in dogs with hypercortisolism (HC) is uncommon. OBJECTIVES: To evaluate signalment, presentation, treatments, and long-term outcomes of dogs with concurrent HC and SMS. ANIMALS: Thirty-seven dogs. METHODS: Medical records of dogs with HC and concurrent SMS were recruited from 10 institutions. Clinical information, test results, therapeutic responses, and survival times were reviewed. RESULTS: All 37 dogs with HC and SMS had pituitary-dependent hypercortisolism (PDH); 36/37 weighed <20 kg. Signs and test results were typical of PDH aside from SMS, initially diagnosed in all 4 limbs in 9, pelvic limbs of 22, and thoracic limbs of 6 dogs. Hypercortisolism and SMS were diagnosed together in 3 dogs; HC 1-36 months before SMS in 23; SMS 1-12 months before HC in 11. Mitotane or trilostane, given to control HC in 36/37 dogs, improved or resolved HC signs in 28; SMS did not resolve, remaining static or worsening in 31/36 dogs, mildly improving in 5/19 dogs given additional therapies. Progression of SMS included additional limbs in 10 dogs and the masticatory muscles of 2. The median survival time from diagnosis of SMS was 965 days (range, 8-1188). CONCLUSIONS AND CLINICAL IMPORTANCE: Concurrent SMS and HC is uncommon, possibly affecting only dogs with PDH. Development of SMS might occur before or after diagnosis of HC. Apart from SMS, the clinical picture and survival time of these dogs seem indistinguishable from those of dogs with HC in general. However, while muscle weakness usually resolves with HC treatment SMS does not.

Phase 4 Multinational Multicenter Retrospective and Prospective Real-World Study of Nivolumab in Recurrent and Metastatic Squamous Cell Carcinoma of the Head and Neck.

This study examined the real-world use of nivolumab in patients with recurrent/metastatic squamous cell carcinoma of the head and neck (R/M SCCHN). This was a multinational retrospective study (VOLUME) assessing treatment effectiveness and safety outcomes and a prospective study (VOLUME-PRO) assessing HRQoL and patient-reported symptoms. There were 447 and 51 patients in VOLUME and VOLUME-PRO, respectively. Across both studies, the median age was 64.0 years, 80.9% were male, and 52.6% were former smokers. Clinical outcomes of interest included real-world overall survival (rwOS) and real-world progression-free survival (rwPFS). The median rwOS was 9.2 months. Among patients with at least one assessment, 21.7% reported their best response as 'partial response', with 3.9% reporting 'complete response'. The median duration of response (DoR) and median rwPFS were 11.0 months and 3.9 months, respectively. At baseline, VOLUME-PRO patients reported difficulties relating to fatigue, physical and sexual functioning, dyspnea, nausea, sticky saliva, dry mouth, pain/discomfort, mobility, and financial difficulties. There were improvements in social functioning and financial difficulties throughout the study; however, no other clinically meaningful changes were noted. No new safety concerns were identified. This real-world, multinational, multicenter, retrospective and prospective study supports the effectiveness and safety of nivolumab for R/M SCCHN patients.

Pharmaceutical evaluation of compounded trilostane products.

Compounded trilostane capsules (15 mg, 45 mg, or 100 mg) were purchased from eight pharmacies and assayed for content and dissolution characteristics. Capsules made in-house containing either inert material or 15 mg of the licensed product and proprietary capsules (30 mg and 60 mg) served as controls. Findings were compared with regulatory specifications for the licensed product. Altogether, 96 batches of compounded trilostane and 16 control batches underwent analysis. In total, 36 of 96 (38%) compounded batches were below the acceptance criteria for content. The average percentage label claim (% LC) for each batch ranged from 39% to 152.6% (mean, 97.0%). The range of average % LC for the controls was 96.1-99.6% (mean, 97.7%). The variance in content of the purchased compounded products was substantially greater than for the controls (234.65 versus 1.27; P<0.0001). All control batches exceeded the acceptance criteria for dissolution, but 19 of 96 batches (20%) of purchased compounded products did not. Mean percent dissolution for the purchased compounded products was lower than for controls (75.96% versus 85.12%; P=0.013). These findings indicate that trilostane content of compounded capsules may vary from the prescribed strength, and dissolution characteristics may not match those of the licensed product. The use of compounded trilostane products may therefore negatively impact the management of dogs with hyperadrenocorticism.