Claire R. Sharp

Clinical and immunologic assessment of sepsis and the systemic inflammatory response syndrome in cats

OBJECTIVE To compare clinical findings and inflammatory mediator production among cats with sepsis, cats with noninfectious systemic inflammatory response syndrome (SIRS), and healthy cats. DESIGN Case-control study. ANIMALS Cats with sepsis (n = 16) or SIRS (19) and 8 healthy control cats. PROCEDURES Clinical variables were recorded for each cat, and plasma tumor necrosis factor (TNF) and interleukin (IL)-1β activities and IL-6 and CXC chemokine ligand (CXCL)-8 concentrations were determined at initial evaluation. RESULTS Clinicopathologic abnormalities associated with sepsis in cats included a high band neutrophil percentage, eosinopenia, hyponatremia, hypochloremia, hypoalbuminemia, hypocalcemia, and hyperbilirubinemia. When the sepsis and SIRS groups were compared, the only significant differences in the CBC and plasma biochemical findings were band neutrophil percentage and albumin concentration. Cats with sepsis had significantly greater plasma TNF activity than did healthy cats and were more likely to have detectable concentrations of IL-6 than were cats with SIRS or healthy cats. Plasma IL-1β activity did not differ among groups, and CXCL-8 was not detectable in most (32/43) cats. Mortality rate was not significantly greater for cats with sepsis (7/16) than for cats with SIRS (5/19). Plasma IL-1β activity and IL-6 and chloride concentrations were the only variables correlated with nonsurvival in the sepsis group. CONCLUSIONS AND CLINICAL RELEVANCE Cats with sepsis may have various clinicopathologic abnormalities but are more likely to have a high band neutrophil percentage and hypoalbuminemia than cats with noninfectious SIRS. Plasma interleukin-1β activity and plasma IL-6 and chloride concentrations may be useful prognostic biomarkers for septic cats.

Multicenter prospective evaluation of dogs with trauma

OBJECTIVE To determine hospital admission variables for dogs with trauma including values determined with scoring systems (animal trauma triage [ATT], modified Glasgow coma scale [MGCS], and acute patient physiologic and laboratory evaluation [APPLE] scores) and the usefulness of such variables for the prediction of outcome (death vs survival to hospital discharge). DESIGN Prospective, multicenter, cohort study. ANIMALS 315 client-owned dogs. PROCEDURES By use of a Web-based data capture system, trained personnel prospectively recorded admission ATT, MGCS, and APPLE scores; clinical and laboratory data; and outcome (death vs survival to discharge) for dogs with trauma at 4 veterinary teaching hospitals during an 8-week period. RESULTS Cause of injury was most commonly blunt trauma (173/315 [54.9%]) followed by penetrating trauma (107/315 [34.0%]), or was unknown (35/315 [11.1%]). Of the 315 dogs, 285 (90.5%) survived to hospital discharge. When 16 dogs euthanized because of cost were excluded, dogs with blunt trauma were more likely to survive, compared with dogs with penetrating trauma (OR, 8.5). The ATT (OR, 2.0) and MGCS (OR, 0.47) scores and blood lactate concentration (OR, 1.5) at the time of hospital admission were predictive of outcome. Surgical procedures were performed for 157 (49.8%) dogs; surgery was associated with survival to discharge (OR, 7.1). CONCLUSIONS AND CLINICAL RELEVANCE Results indicated ATT and MGCS scores were useful for prediction of outcome for dogs evaluated because of trauma. Penetrating trauma, low blood lactate concentration, and performance of surgical procedures were predictive of survival to hospital discharge. The methods enabled collection of data for a large number of dogs in a short time.

Plasma Inflammatory Mediator Concentrations at ICU Admission in Dogs with Naturally Developing Sepsis

BACKGROUND Identifying biomarkers to aide in the diagnosis and prognostication of sepsis in dogs would be valuable to veterinarians. OBJECTIVE To compare plasma inflammatory mediator concentrations among dogs with sepsis, noninfectious systemic inflammatory response syndrome (NSIRS), and healthy dogs. ANIMALS Dogs with sepsis (n = 22), NSIRS (n = 23), and healthy dogs (n = 13) presenting to the intensive care unit (ICU) at a veterinary teaching hospital. METHODS Prospective observational study. Clinical parameters were recorded for each dog and plasma tumor necrosis factor (TNF) bioactivity and concentrations of interleukin (IL)-6, CXC chemokine ligand (CXCL)-8 and IL-10 were determined at ICU presentation. RESULTS Dogs with sepsis and NSIRS were significantly more likely to have measurable TNF activity (sepsis 20/22; NSIRS 19/20; healthy 0/13) and IL-6 concentration (sepsis 12/22; NSIRS 15/23; healthy 2/13), than healthy dogs. Healthy dogs (9/13) were significantly more likely to have measurable plasma IL-10 concentrations than dogs with sepsis (4/19), but not NSIRS (7/20). None of the inflammatory mediators evaluated had optimal sensitivity or specificity for the diagnosis of sepsis. Twelve of 22 dogs with sepsis and 15/23 dogs with NSIRS survived to discharge; none of the measured biomarkers correlated with survival to discharge. CONCLUSIONS AND CLINICAL IMPORTANCE Sepsis and NSIRS are associated with increased production of the proinflammatory cytokines TNF and IL-6. In addition, sepsis is associated with decreased production of the anti-inflammatory cytokine IL-10. Despite this, plasma TNF, IL-6, CXCL-8, and IL-10 measured at ICU presentation do not appear to be valuable biomarkers to differentiate sepsis from NSIRS, or predict hospital outcome.

Plasma lactate measurements in healthy cats

Objectives The primary objective was to determine if venous plasma lactate is affected by struggling during venipuncture in clinically normal, healthy cats. Additional objectives were to evaluate the effects of venipuncture site, age, sex, and time (0–24 h) on plasma lactate concentrations in healthy cats. Design Prospective clinical study. Setting Private veterinary referral center. Animals Twenty-one healthy, privately owned, sexually altered, adult cats. Interventions Blood was collected via jugular or medial saphenous venipuncture at the time of study entry and at 6 and 24 hours later. Measurements and Main Results In healthy cats, there were no significant differences in lactate concentrations statified by degree of struggling at time 0 (P = 0.33), time 6 (P = 0.23), or at time 24 (P = 0.41), venipuncture site (P = 0.58), age (P = 0.62), sex (P = 0.06), or time (P = 0.13). Most cats had mild to moderate struggling scores. Venous plasma lactate concentrations for this group of healthy adult cats had a mean of 1.63 mmol/L; 95% CI: 1.34–1.92, SD: 0.62, and a minimum-maximum range of 0.37-2.81 mmol/L. Conclusions The occurrence of mild to moderate struggling during venipuncture, venipuncture site, age, sex, and time did not affect plasma lactate concentrations in this group of healthy cats. Our results suggest that plasma lactate can be reliably measured in cats. Further studies are warranted in sick cats to determine if plasma lactate measurements can be utilized as a diagnostic or prognostic biomarker.OBJECTIVES The primary objective was to determine if venous plasma lactate is affected by struggling during venipuncture in clinically normal, healthy cats. Additional objectives were to evaluate the effects of venipuncture site, age, sex, and time (0-24 h) on plasma lactate concentrations in healthy cats. DESIGN Prospective clinical study. SETTING Private veterinary referral center. ANIMALS Twenty-one healthy, privately owned, sexually altered, adult cats. INTERVENTIONS Blood was collected via jugular or medial saphenous venipuncture at the time of study entry and at 6 and 24 hours later. MEASUREMENTS AND MAIN RESULTS In healthy cats, there were no significant differences in lactate concentrations statified by degree of struggling at time 0 (P = 0.33), time 6 (P = 0.23), or at time 24 (P = 0.41), venipuncture site (P = 0.58), age (P = 0.62), sex (P = 0.06), or time (P = 0.13). Most cats had mild to moderate struggling scores. Venous plasma lactate concentrations for this group of healthy adult cats had a mean of 1.63 mmol/L; 95% CI: 1.34-1.92, SD: 0.62, and a minimum-maximum range of 0.37-2.81 mmol/L. CONCLUSIONS The occurrence of mild to moderate struggling during venipuncture, venipuncture site, age, sex, and time did not affect plasma lactate concentrations in this group of healthy cats. Our results suggest that plasma lactate can be reliably measured in cats. Further studies are warranted in sick cats to determine if plasma lactate measurements can be utilized as a diagnostic or prognostic biomarker.

Systemic response to low-dose endotoxin infusion in cats ☆

Sepsis is a common problem in feline patients and is associated with substantial morbidity and mortality. There has been little research investigating the physiologic response to bacterial infection in cats, in part because appropriate models have not been developed. The objective of this study was to characterize the response to low-dose LPS infusion in conscious, healthy cats. Measures of systemic inflammation, hemodynamic stability, coagulation, metabolic function, and organ damage were compared between placebo and low-dose LPS infusion (2mcg/kg/hx4h, IV) in cats, with each cat serving as its own control. Markers of systemic inflammation including temperature, plasma TNF activity, IL-6, CXCL-8 and IL-10 concentrations were significantly increased and white blood cell counts were significantly decreased after LPS infusion. A biphasic hypotensive response was observed after initiation of LPS infusion without concurrent tachycardia. Additionally, LPS administration significantly increased blood glucose, lactate and creatinine concentrations. Patchy alveolar congestion, multifocal acute alveolar epithelial necrosis, and mild pulmonary edema were noted in the lungs along with acute centrilobular hepatocellular necrosis, and mild lymphocyte apoptosis in the spleen and/or intestinal Peyers patches. No biologically significant alterations in coagulation parameters developed after LPS infusion. Low-dose LPS infusion in cats induced systemic inflammation, hemodynamic derangement, metabolic alterations and mild organ damage. Low-dose endotoxin infusion is a viable pre-clinical model to study naturally developing sepsis in cats.

Chronic Infection of Domestic Cats with Feline Morbillivirus, United States.

To the Editor: Feline morbillivirus (FeMV) was first reported in Hong Kong and mainland China in 2012 (1) and has been associated with tubulointerstitial nephritis, the histopathologic correlate of idiopathic chronic kidney disease (CKD); however, this association has not been proven by studies in FeMV-naive animals. In 2013, phylogenetically related strains were found in Japan, indicating broader geographic distribution in Asia (2). The lack of complete genome sequences for strains from other regions prevents assessment of the clinical relevance and genetic diversity of FeMV. Classical morbilliviruses, such as measles and canine distemper viruses, have a global distribution, suggesting that FeMV might be present elsewhere in the world (3). To confirm the presence of FeMV and assess its genetic diversity and infection patterns in the United States, we collected and analyzed urine samples from domestic cats.

Spontaneous pneumothorax in 35 cats (2001–2010):

Thirty-five cases of spontaneous pneumothorax were reviewed. In contrast to dogs, cats with an established etiology all had spontaneous pneumothorax associated with lung disease. Underlying diseases identified in affected cats included inflammatory airway disease, neoplasia, heartworm infection, pulmonary abscess and lungworm infection. Many cats were managed successfully with observation alone or needle thoracocentesis and specific therapy for their primary lung disease. Cats who present with spontaneous pneumothorax may be treated successfully with non-surgical therapies and appear to have a better prognosis than previously extrapolated from canine studies.

Evaluation of Serum NT-pCNP as a Diagnostic and Prognostic Biomarker for Sepsis in Dogs

BACKGROUND There is a need for diagnostic biomarkers that can rapidly differentiate dogs with sepsis from dogs with noninfectious forms of systemic inflammatory response syndrome (NSIRS). OBJECTIVES To compare serum NT-pCNP concentrations among dogs with various forms of sepsis, NSIRS, and healthy controls and to evaluate the use of serum NT-pCNP for the diagnosis of various forms of sepsis in dogs. ANIMALS One hundred and twelve dogs including 63 critically ill dogs (sepsis n = 29; NSIRS n = 34) and 49 healthy control dogs. METHODS Prospective clinical investigation. Serum samples were collected for NT-pCNP measurement from dogs with sepsis or NSIRS within 24 hours of intensive care unit admission or at the time of presentation for healthy dogs. Dogs with sepsis were subclassified based on the anatomic region of infection. Serum NT-pCNP concentrations were compared among sepsis, NSIRS and healthy groups as well as among sepsis subgroups. The area under the curve (AUC), sensitivity, and specificity for identifying dogs with sepsis were determined. RESULTS Using a cut-off value of 10.1 pmol/L, AUC, sensitivity, and specificity of NT-pCNP for differentiating dogs with sepsis from dogs with NSIRS or healthy control dogs were 0.71 (95% CI, 0.58-0.85), 65.5% (45.7-82.1%), and 89.2% (80.4-94.9%), respectively. Serum NT-pCNP had poor sensitivity for peritoneal sources of sepsis; AUC [0.92 (0.81-1.0)], sensitivity [94% (71-100%)], and specificity [89% (80-95%)] improved when these dogs were excluded. Serum NT-pCNP concentration was not associated with survival in the sepsis group. CONCLUSIONS AND CLINICAL IMPORTANCE Serum NT-pCNP is a promising diagnostic biomarker for sepsis but is a poor indicator of septic peritonitis.

A comparison of total calcium, corrected calcium, and ionized calcium concentrations as indicators of calcium homeostasis among hypoalbuminemic dogs requiring intensive care.

OBJECTIVE (1) To evaluate whether total calcium (tCa) correlates with ionized calcium (iCa) in hypoalbuminemic dogs; (2) to evaluate whether calcium adjusted for albumin (Alb), or total protein (TP), or both accurately predict iCa concentrations and hence can be used to monitor calcium homeostasis in critically ill hypoalbuminemic dogs; and (3) to evaluate factors associated with any potential discrepancy in calcium classification between corrected total and ionized values. DESIGN Prospective observational clinical study. SETTING Small animal intensive care unit in a veterinary medical teaching hospital. ANIMALS Twenty-eight client-owned dogs with hypoalbuminemia. INTERVENTIONS None. MEASUREMENTS AND MAIN RESULTS iCa was determined using ion-specific electrode methodology, on heparinized plasma. The tCa concentration was adjusted for Alb and TP using published equations. In total 29% (8/28) of the hypoalbuminemic, critically ill dogs in this study were hypocalcemic at intensive care unit admission, as determined by iCa measurement. Corrected calcium values failed to accurately classify calcium status in 67.9% and 64.3% of cases, according to whether the Alb-adjusted or TP-adjusted values, respectively, were used. The sensitivity and specificity of the tCa to evaluate hypocalcemia was 100% and 47%, respectively. The sensitivity and specificity of the correction formulae were 37.5% and 79% for the Alb-adjusted values and 37.5% and 74% for TP-adjusted values. tCa overestimated the presence of hypocalcemia and underestimated the presence of normocalcemia, while corrected calcium values overestimated the presence of normocalcemia and underestimated the presence of hypocalcemia. CONCLUSIONS Calcium homeostasis in hypoalbuminemic critically ill dogs should be evaluated by iCa concentrations rather than tCa or calcium adjusted for Alb or TP. Given that tCa has 100% sensitivity for detecting hypocalcemia in this population it is recommended that all hypoalbuminemic and critically ill patients with low tCa should be evaluated with an iCa measurement.

Serum 25-hydroxyvitamin D concentrations in dogs – correlation with health and cancer risk†

25-hydroxyvitamin D (25(OH)D) is important in bone health as well as many diseases including cancer. Supplementation may increase responsiveness of cancer cells to chemotherapy. Serum 25(OH)D, intact parathyroid hormone (iPTH) and canine C-reactive protein (c-CRP) were measured in healthy dogs and dogs with haemoabdomen. Regression analysis determined optimal 25(OH)D concentrations. In healthy dogs (n = 282), mean iPTH concentrations correlated inversely (r(2) = 0.88, P < 0.001) to 25(OH)D concentrations. Variation in both iPTH and c-CRP plateaued at 25(OH)D concentrations of 100-120 ng mL(-1) . Haemoabdomen dogs (n = 63, 43 malignant and 20 benign) had 25(OH)D concentrations ranging from 19.4 to >150 ng mL(-1) . Relative risk of cancer increased with decreasing 25(OH)D concentrations [RR = 3.9 for 25(OH)D below 40 ng mL(-1) (P = 0.0001)]. Serum 25(OH)D concentrations in dogs vary widely, and are influenced by dietary VitD content. Serum vitD measurement can identify dogs for which supplementation may improve health and response to cancer therapy.