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

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

Biomarkers of coagulation and inflammation in dogs after randomized administration of 6% Hydroxyethyl Starch 130/0.4 or Hartmann’s Solution

Synthetic colloid fluids containing hydroxyethyl starch (HES) have been associated with impairment of coagulation in dogs. It is unknown if HES causes coagulation impairment in dogs with naturally occurring critical illness. This study used banked plasma samples from a blinded, randomized clinical trial comparing HES and balanced isotonic crystalloid for bolus fluid therapy in 39 critically ill dogs. Blood was collected prior to fluid administration and 6, 12, and 24 h thereafter. Coagulation biomarkers measured at each time point included prothrombin time, activated partial thromboplastin time, thrombin time, fibrinogen concentration, and the activities of coagulation factors V, VII, VIII, IX, and X, von Willebrand factor antigen, antithrombin, and protein C. Given the links between coagulation and inflammation, cytokine concentrations were also measured, including interleukins 6, 8, 10, and 18, keratinocyte-derived chemokine, and monocyte chemoattractant protein-1. Data were analyzed with linear mixed effects models. No significant treatment-by-time interactions were found for any biomarker, indicating that the pattern of change over time was not modified by treatment. Examining the main effect of time showed significant changes in several coagulation biomarkers and keratinocyte-derived chemokines. This study could not detect evidence of coagulation impairment with HES

Allergy, inflammation, hepatopathy and coagulation biomarkers in dogs with suspected anaphylaxis due to insect envenomation

Objectives: To compare concentrations of biomarkers of; allergy [mast cell tryptase (MCT) and histamine], inflammation [interleukin (IL)-6,-10, and−18, CXCL8, CCL2, keratinocyte chemoattractant (KC), C-reactive protein (CRP)], endothelial glycocalyx shedding (hyaluronan), coagulation [prothrombin time, activated partial thromboplastin time, fibrinogen concentration, and von Willebrand Factor antigen, protein C (PC) and antithrombin (AT) activity], and hepatopathy [alanine transaminase (ALT), aspartate transaminase (AST), alkaline phosphatase (ALP), and total bilirubin] between dogs with anaphylaxis after suspected insect exposure, dogs with critical illness, and healthy dogs. Design: This was a single center prospective clinical observational comparative biomarker study that included 25 dogs with anaphylaxis (evidence of insect exposure, acute dermatological signs, and other organ involvement), 30 dogs with other critical illness, and 20 healthy dogs. Differences across groups in biomarker concentrations were tested using one-way ANOVA or Kruskal-Wallis test, with significant P values (<0.05) reported for pairwise differences detected by post-hoc tests. Logistic regression models were used to calculate the area under the receiver operator characteristic curve (AUROC) for discrimination between anaphylaxis and non-anaphylactic illness. Results: Histamine concentration was significantly higher in the anaphylaxis group than the healthy (P < 0.001) and critically ill groups (P < 0.001), whereas no differences in MCT were detected amongst groups. Biomarker concentrations that were increased relative to healthy dogs in both the anaphylaxis and critically ill groups included IL-10 (P < 0.001 and P = 0.007, respectively), CCL2 (P = 0.007 and P < 0.001, respectively) and AST (both P < 0.001), whereas only the critically ill group had significantly increased CRP (P < 0.001), IL-6 (P < 0.001), KC (P < 0.001), ALP (P < 0.001), and fibrinogen (P = 0.016) concentrations, compared to the healthy group. Only dogs with anaphylaxis had significantly higher hyaluronan (P = 0.021) and ALT (P = 0.021) concentrations, and lower PC (P = 0.030) and AT (P = 0.032) activities, compared to healthy dogs. Both CRP and histamine concentration showed good discrimination between anaphylaxis and other critical illness, with an AUROC of 0.96 (95% CI 0.91–1) and 0.81 (95% CI 0.69–0.93), respectively. Conclusions: This preliminary study in dogs with anaphylaxis after suspected insect exposure, found evidence of an early innate immune response, glycocalyx shedding and anticoagulant consumption. Both CRP and histamine showed potential clinical utility for differentiation between anaphylaxis and other critical illness

Chronic infection of domestic cats with feline morbillivirus, United States

Letter [No abstract available

Veterinary Students’ Knowledge and Perceptions About Antimicrobial Stewardship and Biosecurity—A National Survey

A better understanding of veterinary students’ perceptions, attitudes, and knowledge about antimicrobial stewardship and biosecurity could facilitate more effective education of future veterinarians about these important issues. A multicenter cross-sectional study was performed by administering a questionnaire to veterinary students expected to graduate in 2017 or 2018 in all Australian veterinary schools. Four hundred and seventy-six of 1246 students (38%) completed the survey. Many students were unaware of the high importance of some veterinary drugs to human medicine, specifically enrofloxacin and cefovecin (59% and 47% of responses, respectively). Fewer than 10% of students would use appropriate personal protective equipment in scenarios suggestive of Q fever or psittacosis. Students expected to graduate in 2018 were more likely to select culture and susceptibility testing in companion animal cases (OR 1.89, 95% CI 1.33–2.69, p < 0.001), and were more likely to appropriately avoid antimicrobials in large animal cases (OR 1.75, 95% CI 1.26–2.44, p = 0.001) than those expected to graduate in 2017. However, 2018 graduates were less likely to correctly identify the importance rating of veterinary antimicrobials for human health (OR 0.48, 95% CI 0.34–0.67, p < 0.001) than 2017 graduates. Students reported having a good knowledge of antimicrobial resistance, and combating resistance, but only 34% thought pharmacology teaching was adequate and only 20% said that teaching in lectures matched clinical teaching. Efforts need to be made to harmonize preclinical and clinical teaching, and greater emphasis is needed on appropriate biosecurity and antimicrobial stewardship

Immunohistochemical detection of haemoglobin subunit epsilon (HBE) in the developing mouse placenta

Introduction: Haemoglobin is a widely studied protein due to its important roles in physiology and pathology. Aberrant expression of haemoglobins, including primitive globins, have been reported in various sites and disease states and may have utility in some instances as diagnostic and/or prognostic markers. Despite this, robust detection of haemoglobin epsilon in the placenta during development by immunohistochemistry has not been well documented. Aim: To evaluate a polyclonal antibody against human haemoglobin subunit epsilon (HBE) by immunohistochemistry during primitive erythropoiesis in the developing mouse placenta. Methods and results: An immunohistochemistry protocol was developed using a commercially available anti-human haemoglobin subunit epsilon antibody on the mouse placenta at embryonic day 11.5. Strong and specific cytoplasmic staining was observed in primitive erythroid cells within the blood cell islands. By contrast, the placenta endothelium, mesothelium and mesoderm were all immunonegative for epsilon haemoglobin. Conclusions: An immunohistochemistry protocol for the specific detection of epsilon haemoglobin was successfully developed using mouse placenta tissue. This assay has utility as a tool for the study of erythropoiesis during development and/or detecting the ectopic expression of epsilon globins in disease states such as cancer

2022 Update of the consensus on the rational use of antithrombotics and thrombolytics in Veterinary Critical Care (CURATIVE) Domain 6: Defining rational use of thrombolytics

Objectives To systematically review available evidence and establish guidelines related to the use of thrombolytics for the management of small animals with suspected or confirmed thrombosis. Design PICO (Population, Intervention, Control, and Outcome) questions were formulated, and worksheets completed as part of a standardized and systematic literature evaluation. The population of interest included dogs and cats (considered separately) and arterial and venous thrombosis. The interventions assessed were the use of thrombolytics, compared to no thrombolytics, with or without anticoagulants or antiplatelet agents. Specific protocols for recombinant tissue plasminogen activator were also evaluated. Outcomes assessed included efficacy and safety. Relevant articles were categorized according to level of evidence, quality, and as to whether they supported, were neutral to, or opposed the PICO questions. Conclusions from the PICO worksheets were used to draft guidelines, which were subsequently refined via Delphi surveys undertaken by the Consensus on the Rational Use of Antithrombotics and Thrombolytics in Veterinary Critical Care (CURATIVE) working group. Results Fourteen PICO questions were developed, generating 14 guidelines. The majority of the literature addressing the PICO questions in dogs is experimental studies (level of evidence 3), thus providing insufficient evidence to determine if thrombolysis improves patient-centered outcomes. In cats, literature was more limited and often neutral to the PICO questions, precluding strong evidence-based recommendations for thrombolytic use. Rather, for both species, suggestions are made regarding considerations for when thrombolytic drugs may be considered, the combination of thrombolytics with anticoagulant or antiplatelet drugs, and the choice of thrombolytic agent. Conclusions Substantial additional research is needed to address the role of thrombolytics for the treatment of arterial and venous thrombosis in dogs and cats. Clinical trials with patient-centered outcomes will be most valuable for addressing knowledge gaps in the field

A network approach to addressing the needs of patients with incurable head and neck cancer and their families

Background Patients with incurable head and neck cancer have considerable unmet needs and complex symptom burden, with evidence of substantial geographical and/or socioeconomic inequalities. Accurate information on healthcare needs, resource utilisation and service provision in the last year of life is lacking. This places limits on service delivery planning and the development and testing of interventions to better meet needs. Our partnership spans three regions, which nationally have some of the highest rates of incurable head and neck cancer. Aims The overall aims were to (1) establish a palliative head and neck cancer partnership, (2) identify and evaluate routine incurable head and neck cancer data sources and utilise these to develop and address research priorities. Objectives O1. Develop a palliative head and neck cancer network within the North of England, representing a geographical area with high incidence of incurable head and neck cancer and palliative care needs. O2. Develop and refine research questions and priorities. O3. Engage with data providers to identify relevant data sets and specific data fields to understand the potential quality and utility of these to inform research priorities. Methods There were three interconnected work packages: WP1: A ‘snowballing’ approach to establish a network of clinicians, researchers, patient and public representatives, data architects and key stakeholders with an interest in head and neck cancer palliative care. WP2: A Delphi consensus process to develop and refine research questions and priorities, based on national guidance and systematic reviews of evidence gaps. WP3: Identification of national and local data sets and exploration of the potential data quality and utility, and associated information governance processes for access. Results WP1: A diverse network was established, encompassing members from a wide range of professions and patient/carer groups. WP2: The Delphi consisted of two rounds involving up to 66 participants. Consensus was reached on 12 research questions representing 4 key areas of prioritisation: service provision, symptom management, psychosocial support and information provision and communication. WP3: A range of national and local data sources were identified as having the potential to address the research priorities. A directory of data sources was developed. Working in an iterative way, data sets and relevant data fields were mapped to the 12 potential research priority areas to assess the applicability of using routine data to address these priorities. Limitations Approximately, one-third of participants in the Delphi process dropped out in round 2. Despite attempts to be flexible in our approach, retaining participants, particularly for patients and their families on a palliative care pathway, is challenging. Future work The established network and consensus exercise form the basis for future service evaluations and collaborative research. These will be based on gaps and priorities agreed by patients, their families and a range of other stakeholders. Conclusions The network has established a cross-sectoral collaboration for improving incurable head and neck cancer and a platform to identify 12 research priority areas. Utilising routine data to address these priorities remains a challenging area, and a range of methodological research approaches will be required to take this forward. Funding This article presents independent research funded by the National Institute for Health and Care Research (NIHR) Health Technology Assessment programme as award number NIHR135361