Analysis of factors influencing prognosis in foals with septic arthritis

The purpose of this paper was to identify factors that would positively or negatively affect the short-term survival rate of foals with septic arthritis. Medical records of 81 foals (≤seven months of age) with a clinical diagnosis of septic arthritis, referred to the equine hospital at Cornell University Hospital for Animals, between 1994 and 2003 were reviewed. Signalment, age at presentation, number of affected joints, joint fluid parameters, bacterial agents, treatment modalities and year of treatment were compared between survivors and nonsurvivors. Sixty-two of 81 foals (77%) were discharged from the hospital and classified as 'survivors'. Multiple joint involvement and detection of intra-articular Gram-negative, mixed bacterial infection and degenerate neutrophils were negatively associated with short-term survival. Initiation of treatment within 24 hrs of onset of clinical signs and combination of treatment modalities were positively correlated with survival. Further investigation is needed to determine if these two factors have a similar influence on athletic performance.     

Measurement of equine myeloperoxidase (MPO) activity in synovial fluid by a modified MPO assay and evaluation of joint diseases - an initial case study

The aim of this study was to develop a specific myeloperoxidase (MPO) activity assay in the synovial fluid of horses and investigate whether MPO activity is increased in different forms of joint diseases. Synovial fluid samples were taken from affected joints from horses with osteoarthritis, chronic non-septic arthritis and septic arthritis, and from healthy control horses. MPO activity was measured using a specific modified o-dianisidine-assay containing 4-aminobenzoic acid hydrazide as a potent and specific inhibitor of the MPO. This assay is characterized by high reproducibility. The results reveal only a slight elevation of MPO activity in the synovial fluid of horses with osteoarthritis and chronic non-septic arthritis. However, in the cases of septic arthritis a significant increase in MPO activity was found when compared to the controls. In conclusion the first field study suggests that synovial fluid MPO may be used as a marker for septic arthritis in horses.     

Retrospective study of 108 foals with septic osteomyelitis

Objective   To determine the clinical characteristics, short-term outcome and future athletic performance of foals with septic osteomyelitis.
Design   Retrospective clinical study of 108 Thoroughbred foals with radiographic evidence of bone infection that were presented at the Scone Veterinary Hospital between August 1995 and December 2001. Medical records were reviewed and information concerning signalment, the clinical, laboratory and radiographic findings, treatment and outcome was obtained. Racing records were obtained and evaluated for surviving foals that had reached racing age.
Results   Mean age of foals at initial evaluation was 39 days (range 1–180 days); 21 foals had multiple radiographic bone lesions (19.4%), and 76 had concurrent septic arthritis (70.4%). The most frequently affected bones were the femur, tibia and distal phalanx. In total, 87 foals were discharged from the hospital (80.6%), 79 survived long-term to reach racing age and 52 raced (65.8%). Overall, 48% (52/108) of the foals treated for osteomyelitis raced. Foals less than 30 days of age at the time of diagnosis, critically ill foals and those with multiple bones or joints affected were significantly less likely to be discharged from hospital. Multiple septic joints, but not multiple bone involvement, had an unfavourable prognosis for racing.
Conclusions   The prognosis for survival of foals with septic osteomyelitis or osteitis is favourable. Multiple bone or joint involvement is an important short-term prognostic indicator; however, the involvement of multiple joints, but not multiple infected bones, is associated with an unfavourable prognosis for racing.     

Thromboelastography in healthy, sick non-septic and septic neonatal foals

Objectives To evaluate citrated recalcified thromboelastography (TEG) in healthy newborn foals, and to determine intra‐assay, inter‐individual and intra‐individual (at 12 h, 24 h and 7 days after birth) variations. Additionally, to compare TEG variables, haematological values and conventional coagulation profiles from healthy, sick non‐septic, and septic foals. Design Prospective study. Methods The study group comprised 18 healthy, 15 sick non‐septic and 17 septic foals. Two citrated (3.2%; 1 : 9 anticoagulant : blood ratio) blood samples were submitted for haemostatic evaluation using a TEG analyser and conventional coagulation profile. TEG values (R time (R), K time (K), angle (α), maximum amplitude (MA) and G value (G)), complete blood count (CBC) and conventional coagulation profile (prothrombin time (PT), activated partial thromboplastin time (aPTT), fibrinogen concentration (Fib) and antithrombin (AT)) were evaluated. Signalment, presenting complaint, sepsis scores, blood culture results and outcome were taken from the medical records of the sick foals. Results Mean values ± SD for TEG variables in healthy neonatal foals were: R = 11.82 ± 5.35 min, K = 3.06 ± 1.34 min, α= 51.19 ± 12.66 degrees, MA = 55.06 ± 6.67 mm and G = 6361 ± 1700 dyn/cm². Mean coefficients of variation for intra‐assay/inter‐individual/intra‐individual in healthy foals were: R = 3.5/45.2/43.1%; K = 5.3/58.7/28.7%; α= 1.5/24.7/11.9%; MA = 0.3/12.1/6.1%; G = 1.6/26.7/14.7%. Septic foals had significantly greater α, MA and G values than sick non‐septic foals, and significantly greater MA and G than healthy foals, changes that are consistent with hypercoagulability. Weak correlations were detected between TEG variables and haematological or haemostatic values. Conclusions TEG could be used to provide additional information about the haemostatic system in equine neonates.     

Assessment of synovial fluid biomarkers in healthy foals and in foals with tarsocrural osteochondrosis

Although alterations in biomarkers of cartilage turnover in synovial fluid (SF) have been demonstrated in horses with osteochondrosis (OC), there have been few investigations of such alterations in animals <1 year old. In this study tarsocrural SF samples from foals aged 18, 22 and 52 weeks of age were assessed for: (1) ‘turnover’ biomarkers of type II collagen (CPII and C2C) and proteoglycan (CS846 and glycosaminoglycans [GAG]); (2) matrix metalloproteinase (MMP) activity; (3) insulin-like growth factor (IGF)-1; (4) transforming growth factor (TGF)-β1; (5) prostaglandin (PG) E₂; and (6) leukotriene B₄.Using a linear mixed model, the concentration of biomarkers was compared between animals that developed or did not develop radiographic evidence of OC at 24 or 48 weeks of age. The CPII:C2C ratio tended to be higher in OC-affected joints compared to controls at all ages, and this difference was statistically significant at 22 weeks of age. The concentrations of CS846 and IGF-1, and the CS846:GAG ratio were reduced in OC-affected joints relative to controls at 18 weeks of age only. At 52 weeks of age, the PGE₂ concentration was lower in joints with OC. Overall, there appears to be a consistent anabolic shift in type II collagen turnover in juvenile joints affected by OC. Aberrant proteoglycan turnover is not a hallmark of the late repair of this lesion but reduced concentrations of IGF-1 in SF may be associated with early-stage lesions.     

Plasma D-dimer concentration in sick newborn foals

BACKGROUND: Septicemia is associated with a systemic inflammatory response, hemostatic activation, and disseminated intravascular coagulopathy (DIC). HYPOTHESIS: Increased plasma d-dimer concentration occurs in septic neonates and can reliably detect sepsis or DIC, and predict death in ill neonatal foals. ANIMALS: 40 septic, 41 nonseptic hospitalized foals, and 22 healthy neonates. METHODS: Prospective observational clinical study. Blood samples were collected on admission, at 24-48 hours after admission, and at the time of discharge or euthanasia. Plasma d-dimer concentration, clotting times, antithrombin activity, and fibrinogen concentration were determined. RESULTS: On admission, d-dimer concentration values were significantly higher in septic foals (median, 25-75th percentiles; 568, 245-2013 ng/mL) compared with the nonseptic and healthy groups (386, 175-559 and 313, 152-495 ng/mL, respectively), and in septic foals at the age of 2-7 days compared with similar-age nonseptic foals. By means of samples taken at 24-48 hours of hospitalization and a cut-off value of > 2000 ng/mL, D dimer concentration was significantly associated with the diagnosis of septicemia (odds ratio [OR] = 19.6, 95% confidence interval [95% CI] 1.9-203) and death (OR = 8.7, 95% CI 1.8-43). Owing to a high false-positive prediction rate (71%), a normal d-dimer concentration is better at eliminating the diagnosis of sepsis than an increased d-dimer concentration at predicting sepsis. Fifty percent of septic foals had a diagnosis of DIC, but d-dimer concentration was not significantly associated with the diagnosis of DIC. CONCLUSIONS AND CLINICAL IMPORTANCE: Septic foals showed a marked activation of coagulation and fibrinolytic systems and a high prevalence of DIC. Increased plasma d-dimer concentration is significantly associated with the diagnosis of sepsis.     

Synovial fluid proteins in degenerative joint disease in dogs

Concentrations of three immunoglobulins, albumin, ceruloplasmin, alpha-2 macroglobulin and pregnancy zone protein were estimated by immunoelectrophoresis in paired samples of synovial fluid and serum from 12 dogs with degenerative joint disease (DJD) and six normal dogs. The ratios of synovial fluid to serum concentrations (SF/S) of the four non-immunoglobulins showed an almost inverse linear relationship with their molecular weight in both groups. The SF/S were higher in the DJD synovial fluid than in normal synovial fluid. The difference increased with increasing molecular weight and was highly significant for the largest molecules, reflecting an increased permeability and inflammation in the synovial membrane of DJD joints. The SF/S ratios of the three immunoglobulins studied were compared to the diffusion curves of the four non-immunoglobulins. The SF/S ratios of IgM from dogs with DJD exceeded those calculated from the molecular weights. The present observations support the concept that DJD should be considered an inflammatory disease and suggest that immunologic processes may initiate and/or sustain the inflammation.     

Advances in surgical treatment of septic arthritis of the distal interphalangeal joint in cattle: a review

This review describes the indications for surgical treatment of distal interphalangeal joint (DIJ) infection in cattle and presents an overview of former surgical methods that have been modified for current use, including arthrotomy, resection of the distal sesamoid bone, resection of the DIJ and digital amputation. The post-operative life span, reasons for culling, pros and cons of claw-preserving techniques versus digital amputation, and pain management in general are also discussed. It would appear that severe claw diseases that result in septic arthritis of the DIJ do not necessarily lead to a reduced life span if cows are adequately treated and thorough aftercare is provided.     

Association of admission plasma D-dimer concentration with diagnosis and outcome in horses with colic

Background: Coagulopathies detected in horses with gastrointestinal problems seem to be associated with poor outcome. Plasma D‐Dimer concentration is a sensitive test for assessing coagulopathies. Hypothesis: Plasma D‐Dimer concentration tested on admission is related to diagnosis and outcome in horses with colic. Animals: Four hundred and ninety three horses referred for evaluation of abdominal pain. Methods: Prospective observational clinical study. Horses were grouped according to diagnosis (medical and surgical intestinal obstructions, ischemic disorders with and without intestinal resection, enteritis, peritonitis), outcome (survivors, nonsurvivors), and number of coagulopathies (normal profile, 1 or 2 coagulopathies, subclinical disseminated intravascular coagulation [DIC]). Blood samples were collected on admission and plasma D‐Dimer concentration, clotting times (PT and aPTT), and antithrombin activity were determined. Positive likelihood ratios (LR+) were calculated for evaluation of D‐Dimer cut‐off values, which were later tested in a logistic regression model. Results: Horses with enteritis or peritonitis had significantly (P < .001) higher plasma D‐Dimer concentrations and more severe coagulopathies on admission than horses with other diagnoses. Nonsurvivors also had significantly (P < .001) higher plasma D‐Dimer concentrations at presentation than did survivors, and those horses with subclinical DIC on presentation had an odds ratio (OR) 8.6 (95% confidence interval [CI], 3.3–22.5, P < .001) for nonsurvival. Finally, D‐Dimer concentrations >4,000 ng/mL had a LR+ of 5.9 and an OR 8.8 (95% CI, 4.5–17.1, P < .001) for nonsurvival. Conclusion and Clinical Importance: Plasma D‐Dimer concentration measured on admission can be used to facilitate diagnosis and outcome prediction in horses with colic. A potential cut‐off value for nonsurvival was found at approximately 4,000 ng/mL.     

Cervical Vertebral Osteomyelitis With Secondary Septic Arthritis of the Atlantoaxial Joint in a Foal: A Case Report

A 36-day-old, 100-kg Thoroughbred colt was presented with a sudden onset of abnormal head carriage and pyrexia. Radiography revealed an osteomyelitis of the vertebral body of the second cervical vertebra. Ultrasonography revealed abscessation in the region of the atlantoaxial articulation on the left side, and fluid aspirated from the abscess confirmed suppurative inflammation. Surgical management was not feasible on economic grounds, and therefore this case was managed with aggressive medical therapy based on the most likely pathogens involved. To provide prolonged antibiotic therapy within the client’s budget, the antibiotic flucloxacillin (Staphlex, 500 mg) was used at a dose of 10 mg/kg by mouth, three times daily. Thirty-eight days after first presentation, the foal was euthanized because of chronic pain and deterioration in neurologic signs. A diagnosis of chronic osteomyelitis of the body of the second cervical vertebra (axis) was made with concurrent septic arthritis of the atlantoaxial joint involving the articular surface of the first cervical vertebra (atlas) and cervical myelopathy of the spinal cord within the first two vertebrae. No pathogens were isolated post mortem. This is the first report to describe the use of flucloxacillin in a foal. Although the outcome was fatal, the medical therapy provided could be considered successful at sterilizing the bony lesion.     

Blood arginine vasopressin, adrenocorticotropin hormone, and cortisol concentrations at admission in septic and critically ill foals and their association with survival

BACKGROUND: Sepsis is an important cause for neonatal foal mortality. The hypothalamic-pituitary-adrenal axis (HPAA) responses to sepsis are well documented in critically ill humans, but limited data exist in foals. The purpose of this study was to evaluate the HPAA response to sepsis in foals, and to associate these endocrine changes with survival. HYPOTHESIS: Blood concentrations of arginine vasopressin (AVP), adrenocorticotropin hormone (ACTH), and cortisol will be higher in septic foals as compared with sick nonseptic and healthy foals. The magnitude of increase in hormone concentration will be negatively associated with survival. ANIMALS: Fifty-one septic, 29 sick nonseptic, and 31 healthy foals of < or =7 days of age were included. METHODS: Blood was collected at admission for analysis. Foals with positive blood culture or sepsis score > or =14 were considered septic. Foals admitted with disease other than sepsis and healthy foals were used as controls. AVP, ACTH, and cortisol concentrations were measured using validated immunoassays. RESULTS: AVP, ACTH, and cortisol concentrations were increased in septic foals. Septic nonsurvivor foals (n = 26/51) had higher plasma ACTH and AVP concentrations than did survivors (n = 25/51). Some septic foals had normal or low cortisol concentrations despite increased ACTH, suggesting relative adrenal insufficiency. AVP, ACTH, and cortisol concentrations were higher in sick nonseptic foals compared with healthy foals. CONCLUSIONS AND CLINICAL IMPORTANCE: Increased plasma AVP and ACTH concentrations in septic foals were associated with mortality. Several septic foals had increased AVP : ACTH and ACTH : cortisol ratios, which indicates relative adenohypophyseal and adrenal insufficiency.     

Plasma adrenocorticotropin, cortisol, and adrenocorticotropin/cortisol ratios in septic and normal-term foals

BACKGROUND: Little information exists on the hypothalamic-pituitary-adrenal axis in septic foals. HYPOTHESIS: The plasma concentrations of adrenocorticotropin (ACTH) and cortisol are expected to be higher in septic foals as compared to normal foals. The concentrations of hormones in septic foals also are expected to differ further depending upon survival. ANIMALS: Twenty-eight control foals and 46 septic foals <14 days of age were included in this study. METHODS: Blood was collected in EDTA once from 28 normal foals born in the University of Georgia or Cornell University equine research herds and from 46 septic foals within 12 hours after admission to 1 of the 3 tertiary care referral centers involved in the study. Septic foal selection was based on a sepsis score of >11 or a positive blood culture. The control foals were age matched to the septic foals in the study. ACTH and cortisol concentrations were measured by a chemiluminescent immunoassay system. RESULTS: Cortisol concentrations in control foals did not vary with age. Septic foals had significantly higher mean ACTH, cortisol, and ACTH/cortisol ratios than did normal foals. Within the septic foal group, 28 foals survived to discharge, and 18 were euthanized or died. The mean age was not significantly different between the septic surviving and nonsurviving foals. The mean ACTH/cortisol ratio was significantly higher in the septic nonsurviving foals as compared to the septic surviving foals. CONCLUSIONS AND CLINICAL IMPORTANCE: Septic foals had higher hormone concentrations as compared to normal foals, which is an expected endocrine response to critical illness. The increased ACTH/cortisol ratio in nonsurviving septic foals in comparison to surviving septic foals could indicate hypothalamic-pituitary-adrenal axis dysfunction at the level of the adrenal gland in critically ill septic foals.     

Risk factors and prognostic variables for survival of foals with radiographic evidence of pulmonary disease

The medical records of 163 neonatal foals that had thoracic radiographs taken within 48 hours of admission to a referral hospital were reviewed. The objectives of this study were (1) to identify risk factors for the development of thoracic radiographic changes and (2) to identify prognostic indicators for survival in foals with radiographic evidence of pulmonary disease. Failure of transfer of passive immunity (IgG concentration < or = 400 mg/dL) was the only risk factor for radiographic evidence of respiratory disease identified by multivariate analysis. Hypoxemic patients (PaO2 < or = 60 mm Hg) were 4.9 times more likely to reveal radiographic abnormalities in a subset of foals for which arterial blood gas results were available. Foals with a serum creatinine concentration > 1.7 mg/dL upon presentation, dyspnea, and a history of dystocia were significantly more likely to die based on the multivariate statistical outcome analysis. An anion gap > or = 20 mEq/dL was strongly associated with nonsurvival in a subset of foals with arterial blood gas results. These hematologic and biochemical variables can be readily obtained during the initial evaluation of sick foals. The presence of a high anion gap appeared to have the greatest clinical impact and may be a useful prognostic indicator in foals with radiographic evidence of respiratory disease. In contrast, the majority of physical examination variables, including evaluation of tachypnea, abnormal respiratory sounds, fever, weakness, and milk reflux from the nares, which are usually obtained during the general respiratory evaluation of foals, were unrelated to outcome.     

Ultrasonographic diagnosis of septic arthritis of the distal interphalangeal joint in cattle

Diagnosis of septic arthritis in the distal interphalangeal joint (SADIJ) is often difficult, particularly when arthrocentesis or probing of the joint space are inconclusive. The aim of this prospective study was to investigate the usefulness of ultrasonography in reinforcing a tentative clinical diagnosis of SADIJ in 60 Holstein–Friesian cows with septic arthritis in one distal interphalangeal joint (DIJ). The diagnosis of septic arthritis was based on the results of clinical examination and radiographic images, as well as surgical findings. The DIJ of the partner claw of the same foot and the normal DIJs of 18 healthy Holstein–Friesian cows were used as controls. Visualisation, echogenicity and flow phenomena of the synovial fluid were assessed ultrasonographically. The size of the dorsal pouch of the distal interphalangeal joint (DPDIJ) was determined by measuring two defined distances.The DPDIJ could be imaged in all cows with SADIJ, although the quality of the image varied from good (63%) or moderate (30%) to poor (7%). The echogenicity of the synovial fluid in joints with SADIJ did not differ from those of the partner claws. Flow phenomena were seen in only 30% of the DPDIJs with septic arthritis and in none of the DPDIJs of the partner claws. The DPDIJ was larger in DIJs with septic arthritis than in those of the partner claws and controls (P < 0.05). The dorsopalmar/plantar distance of the DPDIJ indicated a suitable sensitivity (0.97) and specificity (1.0) for the diagnosis of septic arthritis when a threshold value of 6 mm was used. Ultrasonographic examination of the DIJ appeared to be a reliable method for confirming a tentative clinical diagnosis of septic arthritis in cattle.     

Determination of the unsaturated disaccharides of hyaluronic acid in equine synovial fluid by high-performance liquid chromatography and fluorescence detection

Background

The purpose of this study was to develop and validate an analytical method to determine the presence of hyaluronic acid derived disaccharides in equine synovial fluid.

Findings

A high-performance liquid chromatography method for the determination of hyaluronic acid derived unsaturated disaccharides in equine synovial fluid was developed and validated. The method is based on the measurement of unsaturated disaccharides released by digestion of linear hyaluronic acid molecules. The method showed linearity (r² = 0.996) over the full working concentration range 0.89-30 mg/l. Relative standard deviation of intra- and inter-day precision ranged from of 4.3-6.7% and 7.1-7.8% respectively. The detection limit was 0.3 mg/l corresponding to 20 mg/l in synovial fluid. Accuracy of the assay was 97-103%. This method was evaluated by determining the concentration of unsaturated disaccharides from hyaluronic acid in synovial fluid of horses with lameness in the metacarpo-/metatarsophalangeal joint localized with positive response to intra-articular anesthesia.

Conclusions

The described method is valid for determination of hyaluronic acid derived disaccharides in equine synovial fluid. This method was applied to a larger research project dealing with a new form of intra-articular therapy in horses with arthritic diseases.     

Uroperitoneum in 32 foals: influence of intravenous fluid therapy, infection, and sepsis

Foals may present to a referral hospital with the primary diagnosis of uroperitoneum (UP), or they may develop UP while hospitalized for other reasons. Historical, physical, laboratory, and diagnostic variables of foals presenting with UP were compared to those developing UP while hospitalized. Emphasis was placed on the presence of electrolyte abnormalities, evidence of sepsis or infection, and development of anesthetic complications during surgical correction of the defect. Foals developing UP while in the hospital frequently had a history of dystocia and presented at a very young age (< 48 hours) with primary clinical signs compatible with intrauterine compromise or presumed hypoxic or ischemic insult with or without sepsis. Foals referred with suspected UP often had additional problems unrelated to the urinary system. These foals had hyponatremia and hyperkalemia on presentation, whereas foals receiving intravenous fluid therapy consisting of a balanced electrolyte solution did not develop the classical pattern of electrolyte abnormalities, yet a similar increase in serum creatinine and, frequently, decreasing urine production were noted. Infection was present in 63% of the foals, and 78% of foals revealed signs suggestive of sepsis or infection. Intrauterine compromise, presumed hypoxia or ischemia, and sepsis may predispose foals to development of UP. Anesthetic complications occurred in 16% of the foals undergoing surgical correction of the defect, although hyperkalemia was only present in half of the foals with anesthetic complications.