The influence of trimming of the hoof wall on the damage of laminar tissue after loading: An in vitro study.

Laminitis is associated with failure of the suspensory apparatus of the distal phalanx (SADP) connecting the distal phalanx to the hoof wall. The specific aim of this study was to examine in vitro whether thinning of the hoof wall leading to increased deformability influences the damage of the laminar tissue created by loading of the hoof. Paired cadaver forelimbs from twelve horses were used. For each pair, the hoof wall from one hoof was thinned by 25%; this was ascertained by radiography. The contralateral hooves were used as controls. In a material testing machine, hooves were loaded in a proximodistal direction at 0.5mm/s until a cut-off value of 8kN or 14mm was reached. Afterwards, samples of the SADP were taken for histology. Image-based evaluation of the destruction of the SADP was performed using quantitative histogram analysis. Additionally, three examiners masked to treatment (trimmed/untrimmed) qualitatively evaluated SADP destruction. During hoof loading with forces from 0.5 to 1.8 times the body mass of the donor horses, hooves with thinned hoof wall underwent significantly more deformation (P<0.05). Quantitative histogram analysis detected a shift to higher brightness values and a higher pixel intensity in control hooves, representing disruption in the histologic analysis. Qualitative evaluation of histology sections showed significantly more disruption of the SADP in untrimmed hooves (P=0.03). These results confirm the hypothesis that reduced hoof wall thickness can decrease disruption of laminar tissue in vitro, thus supporting the evaluation of hoof wall reduction as a prophylactic measure in horses at imminent risk of SADP failure.

Citrullinated histone H3, a biomarker of neutrophil extracellular trap formation, predicts the risk of venous thromboembolism in cancer patients.

Essentials Neutrophil extracellular traps (NETs) might play a role in cancer-related coagulopathy. We determined NET biomarkers and followed cancer patients for venous thromboembolism (VTE). We found a constant association with VTE for citrullinated histone H3. Biomarkers of NET formation could reflect a novel pathomechanism of cancer-related VTE. SUMMARY: Background Neutrophil extracellular traps (NETs) are decondensed chromatin fibers that might play a role in the prothrombotic state of cancer patients. Objectives To investigate whether the levels of citrullinated histone H3 (H3Cit), a biomarker for NET formation, cell-free DNA (cfDNA) and nucleosomes predict venous thromboembolism (VTE) in cancer patients. Patients/Methods Nine-hundred and forty-six patients with newly diagnosed cancer or progression after remission were enrolled in this prospective observational cohort study. H3Cit, cfDNA and nucleosome levels were determined at study inclusion, and patients were followed for 2 years. VTE occurred in 89 patients; the cumulative 3-month, 6-month, 12-month and 24-month incidence rates of VTE were 3.7%, 6.0%, 8.1%, and 10.0%, respectively. Results Patients with elevated H3Cit levels (> 75th percentile of its distribution, n = 236) experienced a higher cumulative incidence of VTE (2-year risk of 14.5%) than patients with levels below this cut-off (2-year risk of 8.5%, n = 710). In a competing-risk regression analysis, a 100 ng mL-1 increase in H3Cit level was associated with a 13% relative increase in VTE risk (subdistribution hazard ratio [SHR] 1.13, 95% confidence interval [CI] 1.04-1.22). This association remained after adjustment for high VTE risk and very high VTE risk tumor sites, D-dimer level, and soluble P-selectin level (SHR 1.13, 95% CI 1.04-1.22). The association of elevated nucleosome and cfDNA levels with VTE risk was time-dependent, with associations with a higher risk of VTE only during the first 3-6 months. Conclusion These data suggest that biomarkers of NET formation are associated with the occurrence of VTE in cancer patients, indicating a role of NETs in the pathogenesis of cancer-associated thrombosis.