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2016 American College of Veterinary Internal Medicine (ACVIM) Forum

Clinician's Brief

Internal Medicine

|September 2016

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Differential Diagnoses of Spinal Diseases 

Differential diagnoses of spinal cord diseases are often correlated with neuroanatomic location of the disease. A thorough, proper neurologic examination should always be performed and a list of differential diagnoses generated. 

Different diseases tend to affect different spinal cord regions: C1-C5, C6-T2, T3-L3, L4-S3, and L6-L7. Distinctive neurologic signs are associated with disease of various spinal cord segments. For example, a C1-C5 myelopathy often presents with spinal pain. Disease in the L6-L7 region often can present similarly to musculoskeletal disorders, with lameness the only clinical sign. Appropriate differentials also depend greatly on patient age and breed. For example, a puppy 6 months of age with chronic paraparesis is unlikely to have intervertebral disk disease and more likely to have a congenital or inflammatory condition. Diagnostic testing for spinal disease should start with spinal radiography and progress to MRI, CT, myelography, or CSF analysis as warranted.—da Costa RC

Laboratory Diagnosis & Classification of Anemia 

Traditionally, there are 2 schemes, often used in tandem, for classifying anemia in veterinary patients: 1 based on RBC indices and 1 based on bone marrow responsiveness. A reticulocyte count is likely the easiest, most reliable measure of bone marrow responsiveness in most species (horses excluded). Examination of a blood smear to evaluate distribution, morphology, and quantity of all 3 cell lines (RBCs, WBCs, and platelets) may help provide important information not obtained from the CBC. Certain morphologic changes are caused by specific disease processes; their presence can be helpful in determining an ultimate cause of anemia. 

A reticulocyte count is likely the easiest, most reliable measure of bone marrow responsiveness in most species.

The most common types of hematology analyzers in veterinary medicine are impedance counters, flow cytometers, or a combination of the two. Impedance counters separate and classify RBCs and platelets based on size as well as lyse WBCs to measure nuclei. Flow cytometers use light-scatter principles to evaluate cells and differentiate them based on size, internal structure, and granularity. Regardless of analyzer type, a comprehensive quality-assurance program is imperative to prevent interpretation errors and compromised medical decision-making, which can be caused by unreliable tests or a clinician’s failure to appreciate analyzer limitations.—Grimes C

Fishhook Foreign Bodies in Dogs & Cats

This retrospective study described the radiographic location, retrieval method, complications, and outcomes associated with fishhook foreign bodies. A total of 107 cases (5 cats, 102 dogs) with 111 fishhooks were included. Single-shanked hooks comprised 46.85% of cases and multiple-shanked hooks 53.15%. Common locations for fishhook foreign bodies were the pharyngeal/oral region (34.26%), cervical esophagus (22.52%), and stomach (24.32%); 3 hooks were cutaneously embedded. Multiple-shanked hooks were 2.314 × more likely to be associated with esophageal damage than were single-shanked hooks. Endoscopic retrieval was attempted in 69 cases and successful in 87%, with 9 patients ultimately requiring surgery and 2 suffering esophageal perforation. Survival for all patients was 100%. The authors concluded that neither type of fishhook ingested (single-shanked vs multiple-shanked) nor location affected outcome and survival.—Hardegree A, Barr J, Bishop M, Pashmakova M

Feline Hyperthyroidism Risk Factors

Causes of hyperthyroidism, a common geriatric disease in cats, are poorly understood. Previous studies have shown Siamese, Himalayan, and Burmese cats having a reduced risk for hyperthyroidism. These cats have colorpoint coats as a result of temperature-sensitive mutations in the tyrosinase gene that allow for limited conversion of tyrosine to melanin pigment. 

Tyrosine is essential for synthesis of melanin and thyroid hormones; therefore, tyrosine availability may impact thyroid levels. This retrospective study evaluated the effect of breed, coat color, age, sex, and clinical data to help characterize feline hyperthyroidism. In nonpurebred cats, the effects of coat color and/or pattern, color dilution, base pigment, white markings, and hair length were also assessed. The records of 3934 cats (885 hyperthyroid, 3049 euthyroid) presented to a single veterinary teaching hospital in the United Kingdom were included. 

The authors found that the following populations had an increased risk for hyperthyroidism: domestic longhair cats, cats ≥11 years of age, and female cats. A decreased risk for hyperthyroidism was found in Burmese, Siamese, Persian, Abyssinian, and British shorthair cats when compared with domestic shorthair cats. Coat coloration was not found to be associated with risk for hyperthyroidism in domestic shorthair cats. The authors concluded that further studies are warranted to investigate: 

  • Tyrosine availability and its effect on feline hyperthyroidism 
  • Breed and hair length associations with hyperthyroidism—Crossley VJ

Checklists & Consistent Patient Care

The goals of systems, processes, and checklists are to minimize mistakes, ensure consistent client and patient care, and to optimize outcomes. Checklists can ensure consistency and completeness by reducing the possibility of failures caused by weaknesses in human memory and attention to detail. Checklists should not be used to punish employees but rather should serve as a component of high-quality care. Consistency is achieved by performing tasks the same way each time to achieve accuracy, dependability, and predictability. However, the nature of repetitive work can lead to complacency and loss of attention to detail—issues that can be addressed by using checklists. 

Checklists are composed of all processes necessary to complete a task. Most checklists should be no more than 7 to 12 items long, as longer lists can be daunting. Steps should be in chronologic order. It is important to include items and tasks essential to patient safety and maintenance of client relationships, and it is preferable to have a job title rather than a specific person assigned to list items. Although many people may be involved in completing the checklist, a single person should have ultimate oversight and accountability.—Weinstein PA

Feasibility of a Novel GI Imaging Device for Use in Dogs 

This study evaluated the safety and feasibility of a disposable, fully automated ingestible camera system to image the GI tract in ambulatory dogs. Five ambulatory light-based imaging (ALI) devices were constructed and contained in an 11-mm × 31-mm capsule. Device components included a battery, a light source, 4 autofocusing cameras, an internal memory system, and a microprocessor with an accelerometer that synchronized camera activity with device motion. The device was administered to client-owned dogs (n = 5) via a direct pilling technique. The dogs were food-restricted for 24 hours before the study and for 8 hours following device administration. Free access to water and normal activity were permitted during the study. 

Visualization of the mucosa and image quality were described as excellent for the stomach and small bowel. 

The capsules were successfully retrieved from all dogs within 24 to 36 hours. No adverse events were reported. The capsules recorded a median of 19 713 images (range, 8572-51 683). Visualization of the mucosa and image quality were described as excellent for the stomach and small bowel. The colon was poorly imaged because of retained feces, but the authors suggested that better visualization might be possible with additional preparation. The authors concluded that ALI is safe and feasible in dogs and may expand the role of imaging in dogs with GI signs.—Pomerantz JS, Hardy BT, Sharma A, Solomon JA

Feeding Tubes in CKD Management 

Chronic kidney disease (CKD) patients fed a renal diet will improve clinically—and cats, on average, may live more than twice as long. Many CKD patients with advanced disease have anorexia. This may be aggravated by hypergastrinemia, stomatitis, gastritis, or food aversion or may have metabolic causes (eg, anemia, uremic gastritis, dehydration, metabolic acidosis, hypokalemia, renal secondary hyperparathyroidism). Feeding schedule modification, appetite stimulants, antiemetics, and assisted enteral nutrition can be helpful in these cases. 

Maropitant has been successful in decreasing emesis in cats with CKD and anecdotally may increase food intake in animals not obviously nauseated. Mirtazapine appears to be an effective appetite stimulant in cats when adjunctive. Despite pharmacologic intervention, enteral feeding is often necessary. Whereas esophagostomy tubes have traditionally been selected for short-term use, in the author’s practice, they have been effectively used in long-term CKD management. In the author’s practice, esophagostomy tube placement decreased the need for IV or SC fluid administration and improved dietary and medication compliance. Complications were seen in <30% of patients and most commonly consisted of cellulitis or abscess formation at the insertion site, inadvertent tube removal, or tube clogging. Most complications responded to treatment or husbandry changes.—Ross S

Hypertrophic Cardiomyopathy 

Feline hypertrophic cardiomyopathy (HCM) has an estimated prevalence of 14.5%, and there are few established treatment options. MYK-461, a small molecule modulator of sarcomere contractility, has shown promise in hypertrophy prevention in a mouse model of HCM. Clinical trials for HCM in humans are underway. 

This study aimed to identify the effects of MYK-461 in cats with subclinical HCM and left ventricular outflow tract obstruction (LVOTO). Research cats with HCM and dynamic LVOTO (n = 5) had serial echocardiographic assessments of LV function and outflow tract gradient at various MYK-461 concentrations. Cats were given isoproterenol to increase heart rate and produce obstruction under anesthesia. After a washout period, 3 cats serving as controls received only the drug-delivery vehicle without MYK-461. MYK-461 reduced LVOTO gradients and eliminated systolic anterior motion of the mitral valve in all cats assessed. MYK-461 plasma concentrations and reduction of fractional shortening were linearly correlated. All cats receiving MYK-461 had a significant reduction in fractional shortening, which was not seen in control cats. The authors concluded that MYK-461 relieved LVOTO and generated an exposure-dependent reduction in left ventricular contractility in cats with subclinical HCM. Clinical studies of MYK-461 and other inhibitors of sarcomere contractility in cats with HCM are warranted.—Stern J, Markova S, Ueda Y, et al.

Electrochemotherapy in Private Practice 

Numerous superficial or otherwise easily accessible tumors (eg, squamous cell carcinoma, melanoma, vaccine-associated sarcomas, some tracheal and esophageal tumors) can be treated with electrochemotherapy (ECT). Patients are heavily sedated and treated over 1 to 3 sessions (sometimes more with larger tumors) with 1 of 2 types of probes. ECT relies on alteration of membrane characteristics with electric pulses to more effectively deliver certain chemotherapeutic agents to the cytosol of tumor cells. For certain drugs that have difficulty passing through the cell membrane, delivery is enhanced. Lipophilic drugs see no benefit in uptake with ECT. The technique also causes a transient, induced, reversible reduction in tumor blood flow, which is thought to enhance the efficacy of ECT. After ECT treatment, tumor cells have histologic changes consistent with inflammation and necrosis. Although historically ECT has been more widely used for veterinary cancer patients in Europe and Brazil, there is recent growth in the application of ECT in the United States and Canada.—Tripp C

Fecal Microbiota Transplantation 

The diverse bacteria that populate the mammalian intestinal tract play a critical—but incompletely understood—role in the health of the host. Microbiota refers to the microbial populations present in different ecosystems of the body. The microbiome is the total number of micro-organisms and their genetic material present in the body. Dysbiosis, a state in which the normal microbiota are altered, has been associated with GI disease in humans and dogs. In veterinary medicine, a better characterization of the flora present in both states of health and disease will lead to more targeted therapeutics. 

Fecal Microbiotic Transplantation (FMT) is the infusion of a fecal suspension from a healthy individual into the GI tract of another individual to treat a specific disease. FMT has been used in humans and in veterinary patients. The authors described potential guidelines and procedures for FMT in dogs. Ideally, donors are screened for relevant bacterial, viral, and parasitic enteropathogens and for recent history of antimicrobial or immunosuppressive therapy. A recent study showed no differences between fresh and stored frozen-and-thawed feces. A recent review in humans found that patients with recurrent Clostridium difficile infections had 4-fold greater number of relapses when <50 g of fecal material was used. Donor feces is administered by enema as a suspension via colonoscope or catheter to a volume of ≈10 ml/kg, although less specific volumes have also been used successfully. Prospective clinical studies will be required to better assess the role of FMT in dogs and cats.—Marks SL, Weese JS

Feline Oral Squamous Cell Carcinoma 

Some cancers exhibit more aggressive behavior because of the action of certain growth factor pathways. Several of these pathways known to contribute to some aggressive tumor behaviors were evaluated in this study on feline oral squamous cell carcinoma (FOSCC), along with Bcl11b, a biomarker for head and neck squamous cell carcinoma (HNSCC). 

Biopsies were obtained from cats with FOSCC and immunohistochemistry performed to evaluate expression of Bcl11b, EGFR, Ki67, and VEGF-D. Chi-square tests were used to determine the relationship between the expression of Bcl11b and other receptors and growth factors. Western blots verified the expression of Bcl11b, EGFR, Src, ERK, and VEGF-D on various FOSCC cell lines. The effect of a Src inhibitor, dasatinib, on FOSCC cell lines was also evaluated via Western blot, MTT assay, and ELISA. VEGF-D was expressed in all biopsy specimens, Bcl11b in 79.4%, and EGFR in 85.7%. A correlation approaching statistical significance was found between Bcl11b and EGFR. In all FOSCC lines, pBcl11b, pEGFR, pSrc, pERK, and VEGF-D were expressed. Dasatinib decreased FOSCC cell viability, inhibited Bcl11b activation, and suppressed VEGF production. EGFR stimulation triggered increased activation of EGFR and ERK, increased VEGF/VEGF-D production, and partially rescued FOSCC cells from dasatinib effects. 

Dasatinib could be a viable option for treating FOSCC, as this study showed an inhibitory effect on cell growth, EFGR, and decreased VEGF production. The authors concluded that dasatinib may have antiproliferative and antiangiogenic effects in FOSCC, although more studies are warranted.—Harris K, Gelberg H, Helfand S

For global readers, a calculator to convert laboratory values, dosages, and other measurements to SI units can be found here.

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