Abstract
In this article, which is part of the Currents in One Health series, principles of immunotherapeutics are discussed and their clinical exploration in dogs reviewed with emphasis on their translatability for improving treatment of commonly diagnosed cancers. With increasing longevity and sustained quality of life in pet dogs through dietary, environmental awareness, and preventative medical practices, the geriatric pet population has continued to steadily grow and, consequently, so have age-related pathologies. Not surprisingly, cancer is the most common cause of mortality in elderly dogs, accounting for 1 in 4 deaths in dogs > 10 years of age. Importantly, some cancer types that arise spontaneously in pet dogs are similar to cancers afflicting people. The shared clinical and biological behaviors of certain cancers observed in pet dogs and people underscore the opportunity to leverage comparative oncology studies, which can accelerate the validation and clinical implementation of innovative therapies that can benefit pet dogs and ultimately guide these strategies toward clinical practice in people too. In the era of immunotherapy, the inclusion of pet dogs that develop cancers under an intact immune system affords a unique and high-value opportunity to study the evolving nature of cancers shaped by immunosurveillance pressures. Complementing these discovery efforts and through a comparative oncology approach, the exploration and clinical validation of novel immunotherapeutic strategies in pet dogs can be foundational for defining the safety and immune-activating potential of new anticancer immune approaches that hold promise to transform cancer treatment in both pets and people alike.
Abstract
OBJECTIVE
Use 18 years of dual-energy x-ray absorptiometry (DEXA) scan data to characterize how body composition changes with age in dogs and cats.
METHODS
This was a retrospective observational study using data obtained from DEXA scans performed between 2006 and 2023. A total of 6,973 observations from 1,273 colony-housed dogs ≤ 1 to 16.1 years old and 6,593 observations from 1,096 colony-housed cats ≤ 1 to 16.9 years old were obtained. Animal ages were rounded to the nearest 1/10-year intervals. Means for each interval were calculated and quadratic, cubic, and quartic polynomial models were fit to assess trends over age.
RESULTS
Age had an effect on all DEXA measurements. In dogs, lean mass increased early in life before slowing to a peak at age 6.3 and then declined gradually. Fat mass also increased until slowing to a peak at age 9.3 and then decreased. In cats, lean mass increased before slowing to a peak at age 4.5, decreased gradually until age 12.5, and then sharply declined. Fat mass increased until slowing to a peak at age 7.5 and then decreased gradually.
CONCLUSIONS
This retrospective study provides a baseline for how body composition changes with age. Results suggest that lean mass loss may begin earlier than previously reported in dogs and cats.
CLINICAL RELEVANCE
Sarcopenia and obesity are common conditions in aging pets. Results can be used to improve body composition assessment of patients and investigate the efficacy of nutritional interventions.
Abstract
OBJECTIVE
To provide a video tutorial on use of the Value Matrix in clinical practice.
ANIMALS
Any animal for which a preference-sensitive decision can be made regarding their care.
METHODS
The veterinary professional gathers a comprehensive history from the veterinary client and uses this information, in further discussion with the client, to develop 2 or more evidence-informed options for the veterinary patient’s care. With the use of the Value Matrix, options are captured on a whiteboard or piece of paper, and the advantages and disadvantages of each option as well as financial cost are visually presented and discussed.
RESULTS
The Value Matrix is a clinical-communication tool for supporting shared decision-making between veterinary professionals and clients and for delivering the Spectrum of Care.
CLINICAL RELEVANCE
The Value Matrix is a practical tool that can assist veterinary professionals in collaborating with clients on making preference-sensitive decisions, providing contextualized care, and achieving informed-client consent.
Abstract
OBJECTIVE
Use finite element analysis to evaluate the biomechanical effects of spinal decompression procedures in healthy Beagle dogs, comparing individualized mini-hemilaminectomy–corpectomy (iMHC), mini-hemilaminectomy, partial lateral corpectomy (PLC), and hemilaminectomy.
METHODS
A finite element model of the L1-L2 functional spinal unit was generated using CT data. For each decompression model, loads were applied in 0.2-Nm steps (maximum, 2.0 Nm) in 6 directions: flexion, extension, right and left lateral bending, and right and left axial rotation. The L1 spinous process tip displacement angle was quantified numerically.
RESULTS
Among the 4 techniques, mini-hemilaminectomy exhibited the smallest displacement angles across all directions. Hemilaminectomy exhibited the largest displacement angles in extension, flexion, right rotation, and left rotation across all techniques. Left and right lateral bending displacement angles were marginally larger for iMHC than for hemilaminectomy at 0.4 Nm; however, at 2.0 Nm, displacement angles were similar.
CONCLUSIONS
Mini-hemilaminectomy minimizes functional spinal unit instability to the greatest extent. Hemilaminectomy is more unstable than iMHC and PLC in flexion, extension, and rotation. Mini-hemilaminectomy–corpectomy and PLC are more unstable than hemilaminectomy in lateral bending, with iMHC being slightly more unstable than PLC or nearly equal.
CLINICAL RELEVANCE
Mini-hemilaminectomy minimizes instability to the greatest extent in cases of ventrolateral spinal compression. In cases of ventral spinal compression, iMHC may be preferable to PLC for providing equivalent stability without impeding spinal cord visualization, but both techniques can cause instability depending on loading direction, so careful attention to postoperative instability is necessary when excessive vertebral body resection is involved.
Abstract
OBJECTIVE
To utilize sidestream dark field video microscopic technology to evaluate the endothelium in a canine hemorrhagic shock and resuscitation model.
METHODS
6 purpose-bred adult dogs were anesthetized, instrumented, and subjected to hemorrhagic shock from September 2021 through June 2022. Each dog was resuscitated with 5 resuscitation strategies in an experimental crossover design study: (1) lactated Ringer’s solution (LRS) and hydroxyethyl starch (HES) solution; (2) canine chilled whole blood (CWB); (3) canine fresh frozen plasma (FFP) and packed RBCs (pRBC); (4) canine freeze-dried plasma (FDP) and hemoglobin-based oxygen carrier (HBOC); or (5) HBOC/FDP and canine lyophilized platelets. Sidestream dark field video microscopic evaluation was performed at 5 time points: commencement, after hemorrhage, after shock, after resuscitation (T135), and conclusion (T180).
RESULTS
There was a significant difference between the perfused boundary region (PBR) measurements when comparing the LRS/HES resuscitation arm to the CWB and FFP/pRBC resuscitation arms at T180. A significant difference in PBR was appreciated in the LRS/HES arm at T135 and T180 compared to its baseline. No other significant differences in PBR were appreciated when resuscitation arms were compared longitudinally or to each other.
CONCLUSIONS
Shelf-stable blood products preserved the endothelial glycocalyx similarly to CWB and pRBC/FFP as evaluated by sidestream dark field video microscopy. Lactated Ringer and HES solutions did not adequately preserve the endothelial glycocalyx compared to CWB and pRBC/FFP.
CLINICAL RELEVANCE
Shelf-stable blood products are a viable option to preserve the endothelial glycocalyx when used during hemorrhagic resuscitation in dogs.
Abstract
OBJECTIVE
Cruciate ligament rupture (CR) in Labrador Retrievers is a complex polygenic disease with high heritability. The environmental contribution to CR risk remains poorly characterized. An accurate genetic risk test for CR in the Labrador Retriever has been developed. This enables evaluation of environmental risk with knowledge of genetic disease predisposition through study of dogs with phenotypic disease status that is discordant with their genetic risk. The objective of this study was to identify environmental factors that contribute to CR in Labrador Retrievers through evaluation of dogs with clinical phenotypes that are discordantly predicted with the use of genetic markers.
METHODS
Dogs were prospectively recruited between January 2013 and December 2022. To study discordant subjects, case dogs with a posterior risk probability value < 0.75 and control dogs with a posterior risk probability of > 0.25, determined with the use of an average of 8 statistical models, were selected. The environmental factors investigated were neuter status, age of neuter, withers height measured at the dorsal-most ridge between the scapulae, weight, body mass index, and athletic activity.
RESULTS
Ninety three dogs were discordant: 58 dogs were discordant CR cases, and 35 dogs were discordant CR controls. Neutering before 12 months of age was a significant risk factor for CR development. Sex, neuter status, or status as an athlete was not associated with CR risk.
CONCLUSIONS
Neutering before 12 months of age influences risk of CR in Labrador Retrievers.
CLINICAL RELEVANCE
This information can inform management decisions about Labrador Retrievers regarding age of neutering, body condition, and athletic activity. The primary factor influencing CR development in Labrador Retrievers is polygenic intrinsic genetic risk.
Abstract
OBJECTIVE
To measure and model concentrations of the analgesic L-carvone, a natural component of spearmint, over time when administered IM to sheep and to characterize L-carvone’s effects on CBCs and clinical biochemistry panels.
METHODS
L-carvone formulated as a 50% solution (v/v) in ethanol and propylene glycol was administered at 71.6 mg/kg IM, split between each semitendinosus muscle in 6 sheep. Venous blood was sampled over 24 hours, and plasma was separated by centrifugation. Additional blood was collected for CBC and serum biochemical analysis, and tissues were sampled after euthanasia. L-carvone concentrations in plasma and tissue homogenates were measured using HPLC-MS-MS. Plasma pharmacokinetic data were described using a nonlinear mixed effects model. Complete blood count and biochemistry data were compared to baseline values using repeated-measures ANOVA and Holm-Šidák tests (P < .05).
RESULTS
Maximum plasma concentrations ranged from 0.28 to 1.93 µg/mL and occurred within 9 to 15 minutes after injection. Pharmacokinetics were best described using 2 compartments. Elimination half-life was 33.7 minutes and 390.2 minutes in the central and peripheral compartments, respectively. Mild increases in neutrophil count and significant increases in creatinine kinase and aspartate aminotransferase were associated with injection site myonecrosis. No physical examination, behavioral, or other clinically significant laboratory changes were noted.
CONCLUSIONS
Intramuscular L-carvone exhibits rapid time to peak concentration, relatively slow plasma elimination, and low tissue concentrations after 24 hours.
CLINICAL RELEVANCE
L-carvone exhibits a favorable pharmacokinetic profile for an analgesic drug. A new L-carvone formulation or administration route is needed to reduce inflammation and necrosis at the injection site.
Abstract
OBJECTIVE
To investigate the prevalence and severity of intervertebral disc (IVD) degeneration (IVDD) throughout the spine of young, middle-aged, and old asymptomatic cats; identify differences between the cervical, thoracic, and lumbar spine; and investigate the influence of sex and neuter status on the prevalence of feline IVDD.
METHODS
60 cadavers were collected from asymptomatic cats and subdivided into 3 age groups: young (≥ 1 to < 6 years), middle aged (≥ 6 to < 12 years), and old (≥ 12 years). T2 weighted sagittal MRI studies of the spine were obtained. Each IVD was graded according to the modified Pfirrmann grading for feline IVDD. Cumulative link mixed models were used to analyze the significance of spinal region, age, sex, and neuter status on the degenerative state of the IVDs.
RESULTS
A total of 1,544 IVDs were evaluated; 884 (57.3%), 425 (27.5%), 147 (9.5%), 82 (5.3%), and 6 (0.4%) were graded Pfirrmann 1, 2, 3, 4, and 5, respectively. Irrespective of spinal region, middle-aged cats (OR, 4.03; P < .01) and old cats (OR, 12.5; P < .01) had significantly higher odds for IVDD compared to young cats. For old cats, thoracic (OR, 4.44; P < .01) and cervical IVDs (OR, 2.76; P < .01) had significantly higher odds of degenerating compared to lumbar IVDs. No significant effect of sex (P = .81) and neuter status (P = .61) was found.
CLINICAL RELEVANCE
The prevalence of feline IVDD significantly increases with progressive age, with the thoracic and cervical IVDs showing the highest odds for degeneration. However, extreme stages of IVDD were only occasionally observed.
Abstract
OBJECTIVE
To characterize cystometry in conscious and anesthetized sheep, including bladder response to sacral root electrical stimulation, thereby providing a baseline set of values.
METHODS
Single-fill cystometries were repeated in adult mule ewes both conscious (n = 5) and under general anesthesia (18) using a commercial system. Parameters including bladder capacity, detrusor (bladder) pressure, urethral opening pressure, bladder compliance, number of nonvoiding detrusor contractions, and bladder pressure change in response to electrical stimulation of the sacral roots under general anesthesia are reported. Pubmed, Embase, and Web of Science databases were searched for studies relating to ovine cystometry, and a systematic review was conducted.
RESULTS
In awake sheep, mean ± SD bladder capacity was 79.6 ± 32.2 mL, urethral opening pressure was 26.0 ± 10.7 cm H2O, and compliance was 3.5 ± 1.9 mL/cm H2O. Peak detrusor pressures during micturition reached 57.7 ± 28.3 cm H2O. In anesthetized animals, mean bladder capacity (endpoint, 50 cm H2O) was 333 ± 191 mL, and mean bladder compliance was 7.7 ± 4.9 mL/cm H2O. Values for these parameters from our systematic review are presented for comparison and reference. Electrical stimulation of the second and third sacral roots caused a greater increase in detrusor pressure than stimulation of the first and fourth sacral roots.
CONCLUSIONS
We present a comprehensive set of data for normal cystometry parameters in sheep, including the first report of detrusor response to sacral root stimulation in anesthetized sheep.
CLINICAL RELEVANCE
This report provides a valuable set of baseline values for a potential translational model of value to neurourologic research and may be a useful reference for clinicians.
