Identification of Predictive Markers of Response to Immunomodulators in the Treatment of COVID-19 Patients.

BACKGROUND: Proper identification of patients at risk of developing serious disease in the context of SARS-CoV-2 infection, as well as the initiation of early treatment, is one of the fundamental elements for successful management of COVID-19. The main objective of this study was to evaluate the usefulness of serum biomarkers (neutrophils, lymphocytes, C-reactive protein, lactate dehydrogenase, D-dimer, ferritin, and interleukin-6) to predict the early response to immunosuppressant therapy in COVID-19 patients. METHODS: This is a case-control study nested in a retrospective cohort, which included hospitalized patients with interstitial pneumonia and with elevation of some proinflammatory parameters. Each of the individuals who died during the 28-day follow-up was defined as a case. For each case, 4 controls were selected, matched by age, gender, and comorbidities. RESULTS: The initial cohort included 856 patients. The incidence of therapeutic failure in the cohort was 14%, thus we identified a total of 120 cases. After the application of a Cox regression model, high serum concentrations of LDH (> 451 IU/L), ferritin (> 1,014 ng/mL) and D-Dimer (> 1,300 ng/mL) were identified as predictors of poor response to treatment. Highly-specific cut-off points could not be established for any of these biomarkers. CONCLUSIONS: Some inflammatory biomarkers, such as LDH, ferritin, and D-dimer, may be helpful in identifying patients for whom an early immunomodulatory therapeutic intervention should be considered in the treatment of COVID-19 patients with pneumonia.

Acid base imbalances in ill neonatal foals and their association with survival.

REASONS FOR PERFORMING STUDY: Acid-base imbalances observed in human paediatric patients are associated with outcome. Likewise, neonatal foals may have different acid-base imbalances associated with diagnosis or prognosis. OBJECTIVES: To determine acid-base imbalances by the quantitative method in ill neonatal foals and assess their association with diagnosis and prognosis. STUDY DESIGN: Observational prospective clinical study. METHODS: This study included 65 ill neonatal foals (32 septic, 33 nonseptic) admitted to an equine referral hospital from 2005 to 2011with acid-base parameters determined on admission and a control group of 33 healthy neonatal foals. Blood pH, pCO2 , sodium, potassium, chloride, L-lactate, albumin and phosphate concentrations were determined. Bicarbonate, globulin, measured strong ion difference (SIDm ), nonvolatile weak buffer concentrations (Atot ), base excess and its components were calculated. Analysis of covariance (ANCOVA) and multiple linear regression statistical analyses were performed. Results are summarised as mean ± s.d. for normally distributed variables and median [25-75th percentiles] for non-normally distributed ones. RESULTS: A total of 63% of ill foals had respiratory alkalosis and 58.5% had SIDm acidosis. The combination of both alterations was detected in 21 of 65 ill foals and abnormal pH was found in 24 of 65. Compared with healthy foals, ill foals had significantly lower SIDm (nonseptic 31.6 ± 6.3 [P<0.01] and septic 32.0 ± 6.4 [P<0.01] vs. control 40.3 ± 3.1 mmol/l), potassium (nonseptic 3.5 [3.3-3.8; P<0.01] and septic 3.6 [3.2-4.3; P = 0.01] vs. control 4.2 [3.8-4.5] mEq/l) and higher L-lactate (nonseptic 5.1 ± 4.2 [P = 0.01] and septic 5.0 ± 3.7 [P = 0.03] vs. control 2.5 ± 1.3 mmol/l). Significantly higher L-lactate and venous pCO2 were found in nonsurviving (6.4 ± 3.5 mmol/l [P = 0.04] and 51 ± 13 mmHg [P<0.01]) compared with surviving foals. CONCLUSIONS: The most common acid-base imbalances observed in ill foals were respiratory alkalosis, SIDm acidosis or mixed respiratory alkalosis with strong ion acidosis. Increased venous pCO2 and blood L-lactate concentration were associated with poor outcome.

Association Between Necropsy Evidence of Disseminated Intravascular Coagulation and Hemostatic Variables Before Death in Horses With Colic.

BACKGROUND: Disseminated intravascular coagulation (DIC) is frequent in horses with severe gastrointestinal disorders. Postmortem studies have found fibrin microthrombi in tissues of these horses, but studies relating these histopathological findings with antemortem hemostatic data are lacking. HYPOTHESIS: Antemortem classification of coagulopathy is related to the presence and severity of fibrin deposits observed postmortem in horses with severe gastrointestinal disorders. ANIMALS: Antemortem hemostatic profile data and postmortem tissue samples (kidney, lung, liver) from 48 horses with colic. METHODS: Tissue samples were stained with phosphotungstic acid hematoxylin and immunohistochemical methods for histological examination. A fibrin score (grades 0-4) was assigned for each technique, tissue and horse, as well as the presence or absence of DIC at postmortem examination. D-dimer concentration, prothrombin time (PT), activated partial thromboplastin time (aPTT), and antithrombin (AT) activity, as well as the clinicopathological evidence of coagulopathy, were determined from plasma samples collected 0-24 hours before death or euthanasia. Histologic and clinicopathologic data from the same horses were compared retrospectively. RESULTS: No association was found between antemortem classification of coagulopathy and postmortem diagnosis of DIC based on tissue fibrin deposition. None of the hemostatic parameters was significantly different between horses with or without postmortem diagnosis of DIC. There was no association between horses with fibrin in tissues or different cut-offs for D-dimer concentration and postmortem evidence of DIC. CONCLUSIONS AND CLINICAL IMPORTANCE: Abnormalities of the routine clotting profile, including D-dimer concentration, were not useful in predicting histologic evidence of DIC at necropsy in horses with severe gastrointestinal disorders.

Metabolic and endocrine profiles in sick neonatal foals are related to survival.

BACKGROUND: Sick neonatal foals suffer from a variety of endocrine and metabolic derangements that may be related to outcome. There are several hepatic and lipid metabolism blood markers that have never been assessed in neonatal foals. OBJECTIVES: Assess panel of endocrine and metabolic variables in group of sick and healthy neonatal foals in order to describe their relationship with diagnosis and survival. ANIMALS: All neonatal foals referred to Unitat Equina-Fundació Hospital Clínic Veterinari during 3 consecutive foaling seasons and a group of healthy foals. METHODS: Observational prospective study. Blood samples were obtained on admission and, when possible, after 24-48 h of hospitalization and immediately before discharge or death. Measured variables were triglycerides, nonsterified fatty acids, glucose, creatinine, urea, γ-glutamyltransferase, glutamate dehydrogenase (GLDH), insulin, cortisol, bile acids, and adrenocorticotropic hormone (ACTH). ACTH/cortisol and glucose/insulin ratios were calculated. RESULTS: Urea, creatinine, and cortisol had median concentrations in septic and nonseptic foals 2- to 8-fold higher than in the control group (P < .001). Median ACTH concentration in the septic group was approximately 4 times higher than in nonseptic and control foals (P < .001). ACTH/cortisol ratio was significantly lower in sick foals compared to control foals (P < .001). A score was designed including creatinine, GLDH, and cortisol. When ≥ 2 of these variables were altered (P < .001), the foal had 32 times more risk of dying (OR, 31.7; 95% CI, 7.7-130.3). CONCLUSIONS AND CLINICAL IMPORTANCE: Plasma creatinine, GLDH, and cortisol should be determined in sick newborn foals on admission because of their association with survival.

Energy expenditure of critically ill neonatal foals.

REASONS FOR PERFORMING STUDY: Nutritional support in critically ill neonatal foals is of great importance given their high metabolic rate and minimal stores of energy and protein. Nutrient requirements of healthy growing foals have been estimated based on daily milk intake; however, little is known about the resting energy expenditure (REE) of sick foals. OBJECTIVES: To determine REE in critically ill neonatal foals (sepsis and/or hypoxic-ischaemic encephalopathy [HIE] and compare this with REE in control foals. METHODS: Critically ill newborn foals admitted to the Fundació Hospital Clinic Veterinari, Universitat Autònoma de Barcelona, Spain from March 2009 to February 2011 were included in this study. Healthy neonatal foals and foals with nonsystemic conditions were used as controls. Oxygen consumption and CO2 production were measured with a respiratory monitor connected to a tight fitting facemask and REE (kcal/kg bwt/day) was calculated with the abbreviated Weir formula. Measurements were performed within 24 h of admission and repeatedly during hospitalisation. RESULTS: Twenty-seven foals were included (16 critically ill foals and 11 controls) and a total of 47 measurements were performed. In the critically ill, REE was reduced (mean +/- s.e. 49.5 +/- 2.1 kcal/kg bwt/day) on admission relative to the controls. In surviving foals (n = 5), REE before hospital discharge was not different (68.4 +/- 7.0 kcal/kg bwt/day) from control foals (64.8 +/- 2.7 kcal/kg bwt/day). CONCLUSIONS: REE was lower in critically ill foals upon admission (40-50 kcal/kg bwt/day) and normalised before hospital discharge (60-80 kcal/kg bwt/day). POTENTIAL RELEVANCE: Critically ill neonatal foals tolerating enteral feeding would receive approximately their REE when given 10% of their bodyweight in mare's milk daily. For sick neonates unable to tolerate enteral nutrition, provision of 50 kcal/kg bwt/day would be a reasonable goal for parenteral nutrition.

Clinical findings in 10 foals with bacterial meningoencephalitis.

REASONS FOR PERFORMING THE STUDY: Bacterial meningoencephalitis is a severe complication in septic foals and there is scarce and often unclear information in the equine literature. OBJECTIVES: To report the most frequent clinical signs, clinicopathological findings, causative agents, treatments given and outcome of a group of foals with confirmed bacterial meningoencephalitis. METHODS: Foals aged < 6 months of age admitted to the Universitat Autonoma de Barcelona (2004-2009) with confirmed bacterial meningoencephalitis were retrospectively included in the study Diagnosis of bacterial meningoencephalitis was made by cerebrospinal fluid (CSF) culture, CSF analysis consistent with bacterial infection, observation of bacteria in CSF cytology or postmortem confirmation. RESULTS: Nine neonates and one 5-month-old foal were included. The most frequently observed clinical signs were alterations in mental status (10/10), recumbency (8/10), weakness (8/10), abnormal pupillary light reflexes (6/10), decreased suckling-reflex (6/9), seizures and/or nystagmus (4/10). Common clinicopathological alterations included hyperfibrinogenaemia (8/9), hyperlactataemia (7/7), and neutropenia (5/10) or neutrophilia (5/10). Most neonates (8/9) developed bacterial meningoencephalitis despite having a sepsis score near the cut-off value (median = 12). On CSF analysis, pleocytosis (9/9), increased total protein concentration (5/6) and intracellular bacteria (6/9) were detected. The most frequently isolated bacterium was Escherichia coil. Once bacterial meningoencephalitis was diagnosed, antimicrobial therapy was switched to third and fourth generation cephalosporins. CONCLUSIONS: The diagnosis of bacterial meningoencephalitis is established based on CSF analysis and culture. Clinical recognition of bacterial meningoencephalitis is difficult and can be easily overlooked. Moreover, severe sepsis is not necessary to develop bacterial meningoencephalitis. POTENTIAL RELEVANCE: CSF analysis should be considered more often in sick newborn foals with signs indicative of central nervous system (CNS) involvement. Cerebrospinal fluid (CSF) cytology and culture would help to confirm or rule out unnoticed bacterial meningoencephalitis, and to choose appropriate antimicrobial therapy

Synovial fluid D-dimer concentration in foals with septic joint disease.

BACKGROUND: Increased synovial fibrinolytic activity (detected by increases in synovial D-Dimer concentrations) has been observed in different joint diseases in humans and adult horses, presumably in order to minimize fibrin deposition within the joint and thus avoid its detrimental effects. OBJECTIVE: To investigate fibrinolytic pathway activation in joint sepsis in foals by measuring synovial D-Dimer concentrations. ANIMALS: Eighteen septic foals with septic joints, 9 septic foals without septic joints, 9 systemically healthy foals with septic joint, and 3 controls are included. METHODS: Prospective observational clinical study of foals admitted for septic arthritis. Synovial D-Dimer concentration and routine synovial fluid analysis were performed. Diagnosis of joint sepsis was made whenever synovial total nucleated cell count was >30,000 cells/µL, synovial total protein >4 g/dL, and neutrophil percentage of >80%, or synovial fluid culture resulted positive. Results were compared among groups by general lineal models. RESULTS: Synovial D-Dimer concentration was significantly (P < .001) higher in the foals with septic joints compared with foals without joint disease (P < .001). CONCLUSIONS AND CLINICAL IMPORTANCE: Septic joint disease is associated with a marked increase of synovial D-Dimer concentration (marked activation of the fibrinolytic activity) within the affected joint. Although further studies are needed, the measurement of synovial D-Dimer concentration may be considered a complementary diagnostic marker of septic joint disease.

Acid-base imbalances during a 120 km endurance race compared by traditional and simplified strong ion difference methods.

REASONS FOR PERFORMING STUDY: Acid-base disturbances are traditionally assessed using the Henderson-Hasselbach equation. The simplified strong ion approach describes more accurately the complex acid-base and electrolyte abnormalities present in endurance horses. OBJECTIVE: To describe acid-base and electrolytes changes in fit horses competing in a FEI*** 120 km endurance race and to compare the traditional vs. strong ion approaches. METHODS: Thirty horses were initially enrolled in the study. Venous blood samples were obtained before the race (n = 25), at the second (n = 29; 65.4 km) and third vet-gates (n = 23, 97.4 km) and upon race completion (n = 17). Blood gas analysis was performed to determine pH, PCO(2), PO(2), Na(+), K(+) and iCa(++), and calculate HCO(3)(-), base excess and tCO(2). Packed cell volume and total protein, globulin, albumin, lactate, phosphate, glucose and creatinine concentrations, as well as muscle enzymes activities, were also determined. Calculated variables included strong ion difference (SIDm), strong ion gap (SIG) and nonvolatile buffer concentration (A(tot)). A longitudinal linear model using the general estimating equation methodology was used for statistical analysis. RESULTS: Mild but significant increases in PCO(2), SIDm, lactate, plasma protein, globulins and A(tot), as well as a decrease in potassium concentrations were observed from the second vet-gate to race finish when compared to prerace values (P < 0.05). Using the strong ion approach, 67% samples showed acid-base disturbances vs. 70% when using the traditional method, but their interpretations only matched in 24% of measurements. CONCLUSIONS: A complex acid-base imbalance characterised by a mild strong ion alkalosis (hypochloraemia attenuated by hyperlactataemia), nonvolatile buffer acidosis and compensatory mild respiratory acidosis were present in most horses, although pH did not significantly change during a 120 km endurance race. The strong ion approach to interpretation of acid-base balance should be favoured over the traditional approach in endurance horses, given the frequent and complex alterations in PCO(2), SIDm and A(tot) during a race.

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.

Low-molecular-weight heparin dosage in newborn foals.

BACKGROUND: Heparin is used in humans as prophylaxis of hypercoagulable states and disseminated intravascular coagulation (DIC). However, babies need a higher heparin dose than do adults. Septic neonate foals are at high risk of hypercoagulable state and DIC, and there is limited objective information about heparin dose for equine neonates. OBJECTIVE: To assess whether neonate foals require higher dosages of low-molecular-weight heparin (LMWH) than adults. ANIMALS: Eighteen healthy and 11 septic neonate foals. METHODS: Experimental and clinical studies. Firstly, healthy foals were randomly distributed in 2 groups, 1 receiving 50 IU/kg SC of dalteparin and the 2nd group receiving 100 IU/kg SC of dalteparin, once daily for 3 days. Blood samples were collected before and 3, 6, 27, and 51 hours after the 1st LMWH administration. Plasma antifactor-Xa activity was measured, together with hemostatic and hematologic parameters used to assess the risk of bleeding. Subsequently, septic foals were treated blindly either with placebo (saline) or 100 IU/kg of dalteparin for 3 days. Plasma antifactor-Xa activity and other hemostatic parameters were determined before and after treatment. RESULTS: Plasma antifactor-Xa activity in healthy foals was below prophylactic activity when using the adult dosage (50 IU/kg), whereas prophylactic activities were achieved when using the double dosage (100 IU/kg). No hemorrhagic events and erythrocyte-related complications were observed with either dosage. In the clinical study, only 4/6 septic foals had plasma antifactor-Xa activity adequate for prophylaxis. CONCLUSIONS AND CLINICAL IMPORTANCE: Equine neonates require higher dosages of LMWH compared with adults to reach prophylactic heparinemia.

Peritoneal concentrations of transforming growth factor beta in horses with colic.

REASONS FOR PERFORMING THE STUDY: In man, peritoneal transforming growth factor beta (TGF-beta) is associated with peritoneal diseases and subsequent adhesion formation. No studies on plasma and peritoneal TGF-beta concentrations in horses with colic are available. OBJECTIVES: 1) To determine both plasma and peritoneal TGF-beta(1) and TGF-beta(3) concentrations in horses with different types of colic (not previously subjected to abdominal surgery); 2) to compare these concentrations according to the type of peritoneal fluid (transudate, modified transudate and exudate); and 3) to compare and correlate plasma and peritoneal concentrations of TGF-beta(1) and TGF-beta(3) and the types of peritoneal fluid according to the colic group and outcome. METHODS: Peritoneal fluid and plasma samples from 78 horses with colic and 8 healthy horses were obtained. Patients were classified according to diagnosis (obstructions, enteritis, ischaemic disorders and peritonitis), peritoneal fluid analysis (transudate, modified transudate and exudate), and outcome (survivors and nonsurvivors). Plasma and peritoneal TGF-beta(1) and TGF-beta(3) concentrations were determined by ELISA. Data were analysed by parametric and nonparametric tests. P< or =0.05 was considered as statistically significant. RESULTS: Concentrations of peritoneal fluid TGF-beta(1) were significantly (P = 0.01) higher in horses with peritonitis in comparison with all other colic groups and controls. Horses with ischaemic lesions had significantly (P = 0.01) higher concentrations of peritoneal TGF-beta(1) in comparison with controls and the group of horses with obstructions. Peritoneal TGF-beta(1) concentration also was significantly (P = 0.01) higher in exudates in comparison with transudates. Peritoneal TGF-beta(1) and TGF-beta(3) concentrations and plasma TGF-beta(1) concentration were significantly increased in nonsurvivors compared to survivors (P = 0.001, P = 0.004 and P = 0.05, respectively). CONCLUSIONS: Peritoneal TGF-beta(1) concentration was higher in horses with severe gastrointestinal diseases (ischaemic intestinal lesions and peritonitis), in horses with an altered peritoneal fluid (exudate), and in nonsurvivors. POTENTIAL RELEVANCE: Peritoneal TGF-beta concentration increases in horses with severe gastrointestinal disease as an anti-inflammatory response.

Enteral fluid therapy in 108 horses with large colon impactions and dorsal displacements.

To assess the effect of enteral fluid therapy (EFT) in horses with colic, 78 adult horses with colon impactions and 30 with left dorsal colon displacements received an isotonic electrolyte solution via a nasogastric tube at a rate of 8 to 10 l every two hours until resolution of clinical signs. Clinical progression was monitored closely, and plasma biochemistry was evaluated before, during and after treatment. Volume of fluids, time to resolution, and outcome were also recorded. EFT was well tolerated by 102 of 108 horses and was an effective method to resolve 99 per cent of colon impactions and 83 per cent of displacements. For both groups, the mean (sd) time to resolution was 20.2 (5.2) hours and the volume of fluid administered was 118.6 (34.5) l. No relevant abnormalities were observed in most plasma biochemistry parameters during treatment, except for a mild haemodilution effect in 63 per cent of horses.

Uveal inflammation in septic newborn foals.

BACKGROUND: Septicemia in humans is described as a leading cause of uveitis, which eventually can induce blindness. HYPOTHESIS/OBJECTIVES: Uveal inflammatory findings could be related to sepsis severity in newborn foals and might be used as an indirect indicator for survival. ANIMALS: Seventy-four septic foals, 54 nonseptic foals, and 42 healthy foals. METHODS: Prospective observational clinical study. A detailed blinded, ophthalmic examination was performed by boarded ophthalmologists on all admitted newborn foals. Foals were grouped as septic (when blood culture resulted positive or the sepsis score was > or =14), nonseptic, and controls. Based on blood culture results, the septic group was subdivided into bacteremic and nonbacteremic foals. RESULTS: Blood culture was performed in 62/74 septic foals, from which 35 (56%) were bacteremic and 27 (44%) were non-bacteremic. Anterior uveitis was diagnosed in a significantly (P < .005) higher number of septic/bacteremic foals (14/35, 40%) than in septic/nonbacteremic foals (5/27, 19%), nonseptic foals (4/54, 7%), and control foals (0%). Anterior chamber fibrin was only observed in 4/14 (29%) septic/bacteremic foals with anterior uveitis. Anterior uveitis was also associated with posterior uveitis in 6/35 (19%) septic/bacteremic foals. The diagnosis of uveitis was related to nonsurvival (P = .001, odds ratio = 6.2, 95% confidence interval = 2.1-18.2). CONCLUSIONS AND CLINICAL IMPORTANCE: Anterior uveitis is highly prevalent in septic newborn foals, especially in those with a positive blood culture, and it should be considered as a survival prognostic factor.

Effects of blood contamination on peritoneal D-dimer concentration in horses with colic.

BACKGROUND: Peritoneal D-Dimer concentration can be determined to assess peritoneal fibrinolysis activity in horses with gastrointestinal disorders. However, blood contamination of peritoneal fluid may occur during collection and could alter peritoneal D-Dimer concentration. HYPOTHESIS/OBJECTIVES: Blood contamination in peritoneal fluid does not affect interpretation of peritoneal D-Dimer concentration in horses with colic. ANIMALS: Thirty-four horses with colic and 4 healthy horses. METHODS: Peritoneal fluid and blood samples were simultaneously collected upon admission. Then, peritoneal fluid was serially contaminated with the horse's own blood; final contaminations corresponded to 1, 5, 10, and 20% of blood in peritoneal fluid. D-Dimer concentration was determined in blood, peritoneal fluid, and contaminated peritoneal fluid samples. Data were analyzed using a longitudinal linear model and a generalized estimating equations analysis to assess the quantitative and qualitative variations of the effect of blood contamination on peritoneal D-Dimer concentration. RESULTS: Peritoneal D-Dimer concentration was only quantitatively affected when peritoneal fluid was contaminated at 20% of blood. However, when using increasing cut-off values of peritoneal D-Dimer concentration (100, 2,000, 8,000, and 16,000 ng/mL), this effect disappeared at the highest cut-off values (8,000 and 16,000 ng/mL). When peritoneal fluid contamination was grouped as "minimally contaminated" (< or =1% of blood) and "highly contaminated" (> or =5% of blood), no significant differences on D-Dimer concentration between both groups at each cut-off value were observed. CONCLUSIONS AND CLINICAL IMPORTANCE: Although quantitative results of peritoneal D-Dimer concentration could be affected by high levels of blood contamination (> or =20%), interpretation of increased peritoneal fibrinolytic activity was not significantly affected.

Peritoneal D-dimer concentration for assessing peritoneal fibrinolytic activity in horses with colic.

BACKGROUND: Plasma D-dimer concentration is a useful marker to assess systemic coagulation and fibrinolytic activities in humans, dogs, and horses. Peritoneal fibrinolytic activity increases in horses with colic, especially in horses with endotoxin in the peritoneal fluid. HYPOTHESIS/OBJECTIVES: Peritoneal D-dimer concentration can be used to assess peritoneal fibrinolytic activity in horses with severe gastrointestinal (GI) disorders and altered peritoneal fluid. ANIMALS: Two hundred and twenty-one colic horses and 15 control horses. METHODS: Prospective observational clinical study. Blood and peritoneal fluid were collected on admission. Horses were grouped according to diagnosis, peritoneal fluid analysis, and outcome. Peritoneal D-dimer concentration was determined, together with peritoneal tissue-plasminogen activator (t-PA) and plasminogen activator inhibitor (PAI-1) activities. Plasma D-dimer concentration also was measured. RESULTS: Peritoneal D-dimer concentration was significantly higher in all colic groups compared with controls, and in horses with enteritis, peritonitis, and ischemic disorders compared with horses with large intestinal obstructions. Peritoneal D-dimer concentration was significantly higher in horses with altered peritoneal fluid (modified transudate and exudate) compared with horses with normal peritoneal fluid analysis. Plasma D-dimer concentration also was significantly higher in the peritonitis group, and in horses with altered peritoneal fluid analysis. Peritoneal and plasma D-dimer concentrations also were significantly higher in nonsurvivors. Peritoneal d-dimer concentration was significantly correlated with decreased peritoneal t-PA activity and increased peritoneal PAI-1 activity. CONCLUSIONS AND CLINICAL IMPORTANCE: Peritoneal D-dimer concentration is markedly higher in severe GI disorders, and it can be used to assess peritoneal fibrinolytic activity in horses with colic.

Fibrin deposits and organ failure in newborn foals with severe septicemia.

BACKGROUND: Septicemia in human neonates frequently is complicated by activation of the coagulation system, disseminated intravascular coagulation (DIC) and multiple organ failure syndrome, which may contribute to high mortality. In adult horses with DIC, the lung has been the organ most frequently affected by fibrin deposits. In addition, in vivo studies suggest that hemostatic mechanisms may be immature in foals < 1-day old. HYPOTHESIS: Newborn foals with severe septicemia have fibrin deposits in their tissues independently of their age, and these fibrin deposits are associated with organ failure. ANIMALS: Thirty-two septic and 4 nonseptic newborn foals euthanized for poor prognosis. METHODS: Tissue samples (kidney, lung, and liver) collected on postmortem examination were stained with phosphotungstic acid hematoxylin (PTAH) and immunohistochemistry (IHC) for blind histologic examination. A fibrin score (grades 0-4) was established for each tissue sample and for each foal. Medical records were reviewed for assessing clinical evidence of organ failure during hospitalization. RESULTS: Fibrin deposits were found in most septic foals (28/32 when using IHC and 21/32 when using PTAH), independently of the age of the foal. The lung was the most affected tissue (97% of the septic foals). Additionally, organ failure was diagnosed in 18/32 septic foals (8 with respiratory failure, 14 with renal failure), although a statistical association with severe fibrin deposition was not identified. CONCLUSIONS AND CLINICAL IMPORTANCE: Nonsurviving septic foals have fibrin deposits in their tissues, a finding consistent with capillary microthrombosis and DIC.

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.

Effects of athletic taping of the fetlock on distal limb mechanics.

REASONS FOR PERFORMING STUDY: Athletic taping is used frequently by human athletes to stabilise, maintain or strengthen soft tissue structures, but empirical evidence supporting any changes in equine kinematics is lacking. OBJECTIVES: To assess the effects of athletic taping of the fetlock applied by an experienced athletic trainer on forelimb mechanics in healthy horses. HYPOTHESES: That athletic taping of the distal forelimb reduces 1) hyperextension of the fetlock joint during stance, 2) flexion of the fetlock joint during swing and 3) ground reaction forces during stance. METHODS: Ground reaction force and kinematic data were obtained for 6 healthy horses trotting at 3 m/sec for 4 sequential conditions (baseline, untaped; pre-exercise, taped; post exercise, taped post 30 mins trotting exercise; transfer, 4 h after tape removal). Data were analysed using 2-way mixed ANOVAs (condition; joint). RESULTS: A statistically significant interaction was identified for the fetlock during the swing phase (mean +/- s.d. peak flexion at baseline 157 +/- 4 degrees, reduced with taping to 172 +/- 4 degrees; P<0.05) compared with no differences across conditions for the other joints. Peak vertical force reduced significantly (P<0.05) with taping. CONCLUSIONS: Athletic taping of the fetlock does not alter the kinematics of the forelimb during stance, but does limit flexion of the fetlock during the swing phase. The decreased peak vertical force may be due to an increased proprioceptive effect. POTENTIAL RELEVANCE: Reduced peak vertical forces may be of benefit in preventing or reducing injury. Further investigation remains necessary before it can be concluded that taping should be applied for tendinous or ligamentous rehabilitation in equine patients.