The Big Picture in Better Understanding the Equine Foot.

The multiple topics summarized in this article and discussed in detail in this issue of VCNA are comprehensive and in-depth, exploring concepts and clinical experiences for state-of-the-art care of the equine foot. The research on the equine foot will translate to the clinical setting and with this the compassionate care of the horse.

Glucose and insulin response after intravenous and subcutaneous somatostatin administration in healthy horses.

Equine metabolic syndrome (EMS) is prevalent in the equine population, and somatostatin analogs might be useful for diagnosis and/or treatment of EMS in horses. The purpose of this study was to evaluate the glucose and insulin responses to subcutaneous and intravenous administration of somatostatin. Six healthy research horses were included in this prospective study. An initial pilot study was performed to assess several different doses (10-22 µg/kg [4.5-10 µg/lb]) in two horses, then a final dosage of 22 µg/kg (10 µg/lb) was administered to six horses IV and SQ in a two-period randomized cross-over study performed over a 3-month study period. Blood samples were collected for measurement of plasma insulin and glucose concentrations during a 24-hr study period. Both IV and SQ somatostatin resulted in decreased insulin and increased glucose concentrations. SQ somatostatin resulted in a longer clinical effect, with return to baseline insulin occurring at 1.5 hr postadministration, versus 45 min for IV. Both IV and SQ administration of somatostatin to normal horses resulted in decreased insulin and increased glucose concentrations, likely due to suppression of insulin secretion by somatostatin. A more prolonged effect was seen following SQ administration as compared to IV administration, and no adverse effects were noted at varying doses. This study provides additional information regarding the effect of somatostatin administration on insulin and glucose concentrations in clinically healthy horses.

Real-world performance of blood-based proteomic profiling in first-line immunotherapy treatment in advanced stage non-small cell lung cancer.

PURPOSE: Immune checkpoint inhibition (ICI) therapy has improved patient outcomes in advanced non-small cell lung cancer (NSCLC), but better biomarkers are needed. A clinically validated, blood-based proteomic test, or host immune classifier (HIC), was assessed for its ability to predict ICI therapy outcomes in this real-world, prospectively designed, observational study. MATERIALS AND METHODS: The prospectively designed, observational registry study INSIGHT (Clinical Effectiveness Assessment of VeriStrat® Testing and Validation of Immunotherapy Tests in NSCLC Subjects) (NCT03289780) includes 35 US sites having enrolled over 3570 NSCLC patients at any stage and line of therapy. After enrolment and prior to therapy initiation, all patients are tested and designated HIC-Hot (HIC-H) or HIC-Cold (HIC-C). A prespecified interim analysis was performed after 1-year follow-up with the first 2000 enrolled patients. We report the overall survival (OS) of patients with advanced stage (IIIB and IV) NSCLC treated in the first-line (ICI-containing therapies n=284; all first-line therapies n=877), by treatment type and in HIC-defined subgroups. RESULTS: OS for HIC-H patients was longer than OS for HIC-C patients across treatment regimens, including ICI. For patients treated with all ICI regimens, median OS was not reached (95% CI 15.4 to undefined months) for HIC-H (n=196) vs 5.0 months (95% CI 2.9 to 6.4) for HIC-C patients (n=88); HR=0.38 (95% CI 0.27 to 0.53), p<0.0001. For ICI monotherapy, OS was 16.8 vs 2.8 months (HR=0.36 (95% CI 0.22 to 0.58), p<0.0001) and for ICI with chemotherapy OS was unreached vs 6.4 months (HR=0.41 (95% CI 0.26 to 0.67), p=0.0003). HIC results were independent of programmed death ligand 1 (PD-L1). In a subgroup with PD-L1 ≥50% and performance status 0-1, HIC stratified survival significantly for ICI monotherapy but not ICI with chemotherapy. CONCLUSION: Blood-based HIC proteomic testing provides clinically meaningful information for immunotherapy treatment decision in NSCLC independent of PD-L1. The data suggest that HIC-C patients should not be treated with ICI alone regardless of their PD-L1 expression.

Prognostic indicators of poor outcome in horses with laminitis at a tertiary care hospital.

This retrospective study investigated the factors associated with a poor outcome (death by euthanasia or from other causes) in horses treated for laminitis at a tertiary care hospital. Cases (n = 247) were defined as patients with laminitis that were euthanized or that died of other causes during hospitalization. Controls (n = 344) were patients with laminitis that survived to be discharged from the hospital. In the final multivariate analysis, the factors significantly associated with an increased risk for death and their respective odds ratios (OR) were as follows: Thoroughbred (OR = 1.57); racehorse (OR = 1.76); treatment with flunixin meglumine (OR = 1.76); vascular pathology (OR = 2.12); distal displacement of the third phalanx (OR = 2.68); pneumonia (OR = 2.87); and lameness of Obel grade II (OR = 2.99), grade III (OR = 9.63), or grade IV (OR = 20.48). The use of glue-on shoes significantly reduced the risk for death (OR = 0.36).

Home care for horses with chronic laminitis.

Home care for horses with chronic laminitis has been discussed rarely in the veterinary literature even though, at any given time, most of us have at least 1 chronic laminitis case in our care that is being managed at home by the owner. Almost all of our knowledge on this aspect of laminitis treatment has been gleaned through experience, by individually working through the medical, ethical, financial, and emotional challenges these cases can present. Much has already been presented on the medical management of the laminitic horse and on strategies for trimming and shoeing the laminitic foot. This article focuses on the other challenges so often faced when directing the home care of a horse with chronic laminitis.

First aid for the laminitic foot: therapeutic and mechanical support.

The goals of mechanical treatment during the acute phase of laminitis are to preserve the lamellar interface by reducing the forces that are compromising its integrity and to make the horse more comfortable. Early decision making is important in managing acute laminitis. This article helps the practitioner to identify some of the commonly used and accepted methods of protecting the laminitic foot. The materials available and the theories behind their use are also described. The laminitic foot needs to be understood before determining methods for its support. Most treatment options involve shifting the weight-bearing forces from compromised areas of the foot (ie, the lamellar interface) to areas more capable of supporting the patient's weight, remembering that the sum of the forces should remain the same. The many treatment options available allow for flexibility and effective management and permit each modality to be combined in infinite ways for hoof support. The goal of therapy is to support the foot and stop the progression of the disease to the chronic phase.

Evaluation of Circulating Tumor DNA for Methylated BCAT1 and IKZF1 to Detect Recurrence of Stage II/Stage III Colorectal Cancer (CRC).

BACKGROUND: Most recurrences of early-stage colorectal cancer detected with current surveillance measures are widespread and incurable. Circulating tumor DNA (ctDNA) may facilitate earlier diagnosis of recurrent colorectal cancer and improve cancer-related outcomes. METHODS: Plasma from patients undergoing standard surveillance after definitive treatment for stage II/III colorectal cancer was assayed with COLVERA and carcinoembryonic antigen (CEA) at a single time point. Results were correlated with radiographic imaging. Assay performance, including sensitivity and specificity for recurrence, were compared. Impact of potentially confounding variables was also explored. RESULTS: 322 patients were included in the final analysis, and 27 recurrences were documented over a median follow-up period of 15 months. Sensitivity for recurrence was 63% [confidence interval (CI), 42.4-80.6] and 48% (CI, 28.7-68.1) for COLVERA and CEA (≥5 ng/mL), respectively (P = 0.046), while specificity was 91.5% (CI, 87.7-94.4) and 96.3% (CI, 93.4-98.1), respectively (P = 0.016). Smoking and age were independent predictors of CEA but not COLVERA positivity. CONCLUSIONS: COLVERA was more sensitive but less specific than CEA in detecting recurrent colorectal cancer. Short median follow-up may have been responsible for apparent false positives in COLVERA. Studies with serial sampling and longer follow-up are needed to assess whether earlier detection of colorectal cancer recurrence translates into clinical benefit. IMPACT: This prospective study showed that COLVERA (a two-gene ctDNA assay) was more sensitive for detection of recurrence in a cohort of patients undergoing surveillance after definitive therapy for stages II and III colorectal cancer.

Novel dry cryotherapy system for cooling the equine digit.

OBJECTIVES: Digital cryotherapy is commonly used for laminitis prophylaxis and treatment. Currently validated methods for distal limb cryotherapy involve wet application or compression technology. There is a need for a practical, affordable, dry cryotherapy method that effectively cools the digit. The objective of this study was to evaluate the hoof wall surface temperatures (HWSTs) achieved with a novel dry cryotherapy technology. DESIGN: Repeated-measures in vivo experimental study. SETTING: Experimental intervention at a single site. PARTICIPANTS: 6 systemically healthy horses (3 mares, 3 geldings). INTERVENTIONS: Cryotherapy was applied to six horses for eight hours with a commercially available rubber and rubber and welded fabricice boot, which extended proximally to include the foot and pastern. Reusable malleable cold therapy packs were secured against the foot and pastern with the three built-in hook-and-loop fastener panels. PRIMARY AND SECONDARY OUTCOME MEASURES: HWST and pastern surface temperature of the cryotherapy-treated limb, HWST of the control limb and ambient temperature were recorded every five minutes throughout the study period. RESULTS: Results were analysed with mixed-effects multivariable regression analysis. The HWST (median 11.1°C, interquartile range 8.6°C-14.7°C) in the cryotherapy-treated limb was significantly decreased compared with the control limb (median 29.7°C, interquartile range 28.9°C-30.4°C) (P≤0.001). Cryotherapy limb HWST reached a minimum of 6.75°C (median) with an interquartile range of 4.1°C-9.3°C. Minimum HWST was achieved 68 minutes after cryotherapy pack application. CONCLUSIONS: Dry application of cryotherapy significantly reduced HWST and reached minimums below the therapeutic target of 10°C. This cryotherapy method might offer an effective alternative for digital cooling.

Expression of cyclooxygenase-1 and -2 in naturally occurring squamous cell carcinomas in horses.

OBJECTIVE: To assess expression of cyclooxygenase (COX)-1 and -2 in naturally occurring squamous cell carcinomas (SCCs) and the analogous normal tissues in horses. SAMPLE POPULATION: Tissue samples collected from 3 conjunctival, 2 vulvar, 4 preputial, and 5 penile SCCs during surgical excision in 14 horses and from corresponding body regions (conjunctiva [n = 5 horses], vulva [2], prepuce [3], and penis [3]) in 5 horses euthanized for reasons unrelated to neoplasia. PROCEDURES: Tissue samples were snap frozen in liquid nitrogen and stored at -80 degrees C until analysis. Protein was extracted from the frozen tissues, and western blot analyses were performed. Nonneoplastic and abnormal tissues from each body region were run on the same blot, and blots were run in triplicate. Molecular-weight markers and COX-1 and 2 ovine standards (positive control samples) were run concurrently on the gels; negative control samples were not used. RESULTS: All tissues, including the nonneoplastic and SCC tissues, expressed both COX-1 and -2 proteins. CONCLUSIONS AND CLINICAL RELEVANCE: Results indicated that the expression of COX proteins in both nonneoplastic and SCC-affected tissues in horses is markedly different from that in other species. The reason for the potential benefit of COX-2 inhibitors in horses and other species is unknown. Further research needs to be performed to evaluate the efficacy of COX-2 inhibitors as cancer treatments in horses. Investigation of the mechanisms of tumor development in horses should be performed to increase understanding of this disease and ascertain how the mechanisms differ from those in other animals.

Risk factors for development of acute laminitis in horses during hospitalization: 73 cases (1997-2004).

OBJECTIVE: To identify risk factors for development of acute laminitis in horses during hospitalization for illness or injury. DESIGN: Retrospective case-control study. ANIMALS: 73 horses that developed laminitis (case horses) and 146 horses that did not develop laminitis (control horses) during hospitalization. PROCEDURES: Case and control horses were matched in a 2:1 ratio by the date on which each horse was evaluated. Potential risk factors investigated included age, breed, and sex; highest and lowest values recorded during hospitalization for fibrinogen concentration, WBC count, PCV, and total solids concentration; and comorbid disease states, including pneumonia, endotoxemia, diarrhea, medically treated colic, surgically treated colic, pituitary adenoma, retained placenta or metritis, forelimb lameness, hind limb lameness, acute renal failure, and vascular abnormalities. A univariate screening of all potential risk factors was performed to determine which variables should be selected for further analysis. All factors found to be associated with development of laminitis were included in a multivariate conditional logistic regression model. RESULTS: Development of laminitis was marginally associated with lowest and highest fibrinogen concentrations, highest PCV, and lowest total solids concentration and significantly associated with pneumonia, endotoxemia, diarrhea, abdominal surgery for colic, and vascular abnormalities. In the multivariate analysis, only endotoxemia was significantly associated with laminitis. CONCLUSIONS AND CLINICAL RELEVANCE: Endotoxemia is an important risk factor for development of acute laminitis in horses during hospitalization for medical or surgical conditions. Early recognition of endotoxemia, or the potential for it to develop in certain disease states, and initiation of treatment directed at endotoxemia or its consequences may help prevent laminitis in horses during hospitalization.

Vancomycin for the treatment of methicillin-resistant staphylococcal and enterococcal infections in 15 horses.

We retrospectively reviewed the cases of 15 foals and adult horses in which vancomycin was used, alone or in combination with an aminoglycoside, to treat methicillin-resistant staphylococcal and enterococcal infections. Signalment, presenting complaint, history (including history of treatment for the current complaint), results of bacterial culture and antimicrobial susceptibility testing, treatment, and outcome were reviewed. The average vancomycin dosage was 7.5 mg/kg q8h, administered by intravenous infusion over 30 min. The infection resolved in all 7 horses with soft tissue infections and in 6 of the 8 horses with infections involving a bone or a joint, or both. No adverse effects of vancomycin therapy were noted. Although the number of cases is small, our findings suggest that vancomycin, alone or in combination with an aminoglycoside, is safe and effective for the treatment of resistant staphylococcal and enterococcal infections in horses and foals. However, owing to the importance of staphylococci and enterococci in human medicine and the problems with emerging resistance, we recommend that the use of vancomycin in horses be limited to cases in which culture and susceptibility results clearly indicate that this agent is likely to be effective and in which there is no reasonable alternative.

Tracing axons of peripheral nerves in rats: a potential technique to study the equine recurrent laryngeal nerve.

To study the fascicular anatomy of peripheral nerves, three different groups of retrograde axonal tracers were evaluated: fluorophores, horseradish peroxidase conjugated to subunit B of cholera toxin (CT-HRP), and adeno-associated virus (AAV). The hindlimb nerves in rats served as a model to identify the most efficient tracer in regard to labeling axons within peripheral nerves. The rat's tibial and common peroneal nerves were injected with the different tracers and the sciatic nerve was subsequently examined for evidence of labeled axons. The CT-HRP clearly provided the best results in this rat model. Subsequently, CT-HRP was injected into the recurrent laryngeal nerve (RLN) of two horses in order to identify the location and distribution pattern of the RLN axons within the course of the cervical vagus nerve trunk. No labeling could be observed in either of the two horses.

Radiotherapy of a recurrent ossifying fibroma in the paranasal sinuses of a horse.

A 7-year-old female Thoroughbred was admitted with a history of labored breathing, stridor, and exercise intolerance. Examination revealed a mass in the left paranasal sinuses that was determined to be an ossifying fibroma. Initial treatment consisted of surgical removal of the mass alone; however, the mass recurred 9 months after surgery. The mass was again removed, and adjunctive radiotherapy consisting of 3,000 cGy of cobalt radiation was administered. This time, the tumor did not recur for > 6 years. A third surgery was performed to remove the mass, and adjunctive radiotherapy consisting of 4,000 cGy of photon beam radiation from a linear accelerator was administered. The mass did not recur during the subsequent 3 years. Ossifying fibromas are uncommon tumors that frequently recur if incompletely excised. Results in this horse suggest that adjunctive radiotherapy may delay or prevent tumor recurrence in affected horses.

Associations between age or sex and prevalence of gastric ulceration in Standardbred racehorses in training.

OBJECTIVE: To determine associations between age, sex, or medical treatment and prevalence and severity of gastric ulceration in Standardbred racehorses in training. DESIGN: Cross-sectional study. ANIMALS: 224 Standardbred racehorses in training. PROCEDURE: Gastroscopy was performed on each horse, and mucosal ulceration was graded from 0 (normal mucosa, no lesions) to 3 (extensive, often coalescing, lesions with areas of deep ulceration). Associations between age, sex, or treatment and prevalence and severity of ulcers were evaluated. RESULTS: Prevalence of gastric ulceration was 87%. Although there was little association between age and prevalence of ulcers, there was an association between age and severity of ulcers. Most 2-year-old horses (57.7%) had an ulcer score of 0 or 1. In all other age groups, most (58% to 82.61%) of horses had an ulcer score of 2 or 3. Although overall prevalence of ulceration was comparable among sex groups, the relative risk for gastric ulceration increased with age in castrated males, whereas it decreased in females and sexually intact males. CONCLUSIONS AND CLINICAL RELEVANCE: Gastric ulceration is common in Standardbred horses in race training. Severity is higher in horses > or = 3 years of age than in 2-year-old horses. Relative risk for ulceration increases with age in castrated males.

Odds of moderate or severe gastric ulceration in racehorses receiving antiulcer medications.

OBJECTIVE: To determine the odds of moderate or severe gastric ulceration in racehorses treated with various antiulcer medications. DESIGN: Unmatched case-control study. ANIMALS: 798 horses in active race training (252 Thoroughbreds and 546 Standardbreds). Only horses that had been receiving a single antiulcer medication or no antiulcer medication for at least 2 weeks prior to examination were included. PROCEDURE: Gastroscopy was performed on each horse by a single individual who was not aware of the horses' antiulcer treatments, and severity of gastric ulceration was scored. Signalment and medication history were recorded. Logistic regression was used to determine whether identification of moderate or severe ulceration was associated with treatment, age, breed, or sex. Treatments were grouped as no treatment, buffer, sucralfate, histamine type 2 receptor antagonist, compounded omeprazole, proprietary omeprazole at a low dosage, and proprietary omeprazole at a high dosage. RESULTS: Only proprietary omeprazole was associated with significantly lower odds of moderate or severe ulceration, compared with no treatment. Risks of moderate or severe gastric ulceration in horses receiving a buffer, sucralfate, a histamine type 2 receptor antagonist, or compounded omeprazole were not significantly different from risks in horses receiving no antiulcer medication. CONCLUSIONS AND CLINICAL RELEVANCE: Results suggest that the proprietary formulation of omeprazole was associated with a significantly lower risk of moderate or severe gastric ulceration, compared with no treatment, in racehorses in active race training, whereas other antiulcer medications were not.

Use of a pool-raft system for recovery of horses from general anesthesia: 393 horses (1984-2000).

OBJECTIVE: To describe the pool-raft recovery system protocol and to evaluate the clinical outcome in horses that underwent recovery from general anesthesia using this system. DESIGN: Retrospective study. ANIMALS: 393 horses that underwent recovery from general anesthesia in the pool-raft system. PROCEDURE: Anesthetic records were examined from horses recovered from anesthesia in the pool-raft system between January 1984 and December 2000. Complete medical records of horses were examined when available. Information regarding the anesthetic and recovery period was recorded. Horses first recovered from general anesthesia in the pool-raft and, once awake, were transported to a recovery stall and lowered to the floor in a standing position. RESULTS: 351 horses underwent 1 pool-raft recovery, and 42 horses underwent multiple pool-raft recoveries. Most horses were recovered from general anesthesia within the pool-raft system to safeguard repair of a major orthopedic injury. During 471 pool-raft recoveries, 34 (7%) horses had complications within the recovery pool and 62 (13%) had complications within the recovery stall. Deaths resulted from complete failure of internal fixation, pulmonary dysfunction, or a combination of pulmonary dysfunction and fixation failure in 2% (10/471) of horses that underwent pool-raft recoveries. CONCLUSIONS AND CLINICAL RELEVANCE: The pool-raft system is a good option for recovery from general anesthesia. Although not a fail-safe system, it appears to decrease the complications of recovering horses in a high-risk category. Potential disadvantages of this system are added expense and manpower necessary in building, maintenance, and usage, as well as size limitations of the raft itself.

Patient-reported neuropathy and taxane-associated symptoms in a phase 3 trial of nab-paclitaxel plus carboplatin versus solvent-based paclitaxel plus carboplatin for advanced non-small-cell lung cancer.

INTRODUCTION: nab-Paclitaxel (nab-P) is approved, in the United States, in combination with carboplatin for the first-line treatment of advanced non-small-cell lung cancer, based on a randomized phase 3 trial of nab-P plus carboplatin (nab-P/C) versus solvent-based paclitaxel plus carboplatin (sb-P/C). This trial revealed a higher overall response rate (33% versus 25%; p = 0.005) and longer, but not statistically significant, overall and progression-free survival for nab-P/C versus sb-P/C. In addition, nab-P/C demonstrated lower rates of grade 3 or higher peripheral neuropathy, myalgia, arthralgia, and neutropenia but higher rates of anemia and thrombocytopenia. This report analyzes patient and physician assessment of symptoms within this trial. METHODS: Patients completed the taxane subscale of the Functional Assessment of Cancer Therapy questionnaire, which focuses on taxane toxicity, including peripheral neuropathy and neurotoxicity. Mean baseline scores and changes from baseline are reported. Physicians also graded the severity of neuropathy at each patient visit using National Cancer Institute Common Toxicity Criteria. RESULTS: Patients receiving nab-P/C reported significantly less worsening of peripheral neuropathy (p < 0.001), pain (p < 0.001), and hearing loss (p = 0.002). Patient-reported edema was similar between the two treatment arms. In agreement with patient-reported symptoms, the results of a per-treatment cycle physician assessment of peripheral neuropathy also favored nab-P/C over sb-P/C (p < 0.001). CONCLUSION: In this trial of patients receiving first-line treatment for advanced non-small-cell lung cancer, nab-P/C was associated with statistically and clinically significant reductions in patient-reported neuropathy, neuropathic pain in the hands and feet, and hearing loss compared with sb-P/C.

Administration of ATRA to newly diagnosed patients with acute promyelocytic leukemia is delayed contributing to early hemorrhagic death.

We hypothesized that the high early death rate (EDR) due to bleeding in acute promyelocytic leukemia (APL) is in part attributable to delays in all- trans retinoic acid (ATRA). We conducted a retrospective analysis of the timing of ATRA administration. 204 consecutive patients with newly diagnosed APL between 1992 and 2009 were identified. The EDR was 11%. 44% of early deaths occurred in the first week. Hemorrhage accounted for 61% of early deaths. ATRA was ordered the day APL was suspected in 31% of patients. Delays in ATRA administration led to increases in the percentage of early deaths from hemorrhage.