Clinical Investigation of Coagulation Markers for Early Detection of Sepsis-Induced Disseminated Intravascular Coagulation: A Single-Center, Prospective Observational Study.

Disseminated intravascular coagulation (DIC) often complicates sepsis, and its early treatment is crucial for improving patient outcomes. Coagulation markers may enable earlier diagnosis of DIC. The purpose of this study was to evaluate whether the risk of DIC onset can be predicted using coagulation markers. Patients who showed symptoms of systemic inflammatory response syndrome ≥2 and the quick Sequential Organ Failure Assessment score ≥2 points were investigated. All blood samples collected from the time of hospital admission to 7 days postadmission were investigated. Patients were classified according to time of DIC onset (1) no DIC group (not DIC developed), (2) pre-DIC group (DIC onset >24 hours after admission), (3) DIC group (DIC onset at time of the admission) and according to cutoff values of coagulation markers, High group and Low group. Statistical differences were analyzed by log-rank test, Kruskal-Wallis rank test, and Friedman test. A total of 107 patients were enrolled in the study. Soluble fibrin (SF), plasminogen activator inhibitor (PAI)-1, and d-dimer levels were significantly increased even under pre-DIC conditions. Japanese Association for Acute Medicine (JAAM) DIC scores increased significantly over time in the High SF group (≥31.0 µg/mL) and High PAI-1 group (≥49.0 ng/mL), while JAAM DIC scores in the Low SF group remained ≤3 until day 7. We proposed the cutoff values of SF as 31 µg/mL to detect early phase of DIC. Soluble fibrin might be useful not only to predict DIC but also to exclude a diagnosis of DIC.

A case of paraplegia that developed 6 years after thoracic endovascular aortic repair for blunt traumatic aortic injury.

Case: Thoracic endovascular aortic repair (TEVAR) is becoming the standard therapy for blunt thoracic aortic injury (BTAI). However, the long-term outcomes of TEVAR for BTAI remain unclear. A 36-year-old man was admitted to our emergency department with dyspnea. He had been involved in a serious traffic accident 6 years earlier, requiring TEVAR for BTAI. Outcome: Acute heart failure and pneumonia were diagnosed on this admission. His respiratory condition improved, but paraplegia developed 10 h after hospitalization. Magnetic resonance imaging showed an intraspinal longitudinal area of signal hyperintensity, and spinal cord infarction was diagnosed. Conclusion: Although the causal relationship between the TEVAR and spinal cord infarction remains unclear, paraplegia as a long-term complication after TEVAR does not appear to have been reported previously, and so represents a potentially important complication.

Glycosylation and cross-linking in bone type I collagen.

Fibrillar type I collagen is the major organic component in bone, providing a stable template for mineralization. During collagen biosynthesis, specific hydroxylysine residues become glycosylated in the form of galactosyl- and glucosylgalactosyl-hydroxylysine. Furthermore, key glycosylated hydroxylysine residues, α1/2-87, are involved in covalent intermolecular cross-linking. Although cross-linking is crucial for the stability and mineralization of collagen, the biological function of glycosylation in cross-linking is not well understood. In this study, we quantitatively characterized glycosylation of non-cross-linked and cross-linked peptides by biochemical and nanoscale liquid chromatography-high resolution tandem mass spectrometric analyses. The results showed that glycosylation of non-cross-linked hydroxylysine is different from that involved in cross-linking. Among the cross-linked species involving α1/2-87, divalent cross-links were glycosylated with both mono- and disaccharides, whereas the mature, trivalent cross-links were primarily monoglycosylated. Markedly diminished diglycosylation in trivalent cross-links at this locus was also confirmed in type II collagen. The data, together with our recent report (Sricholpech, M., Perdivara, I., Yokoyama, M., Nagaoka, H., Terajima, M., Tomer, K. B., and Yamauchi, M. (2012) Lysyl hydroxylase 3-mediated glucosylation in type I collagen: molecular loci and biological significance. J. Biol. Chem. 287, 22998-23009), indicate that the extent and pattern of glycosylation may regulate cross-link maturation in fibrillar collagen.

Reinforcement therapy using nitric oxide synthase inhibitors against endotoxin shock in dogs.

PURPOSE: Nitric oxide synthase (NOS) inhibitors were confirmed to correct the hypotension associated with septic shock, but the overall prognosis is often pessimistic. The histological findings failed to show any improvement. In fact, some patients even exhibited signs of exacerbation. The purpose of this study was to investigate the therapeutic effects of NOS inhibitors and catecholamines in dogs suffering from endotoxin shock. The histological changes produced by these agents were also evaluated. METHODS: Mongrel dogs were used under midazolam anesthesia. A PiCCO continuous cardiac output monitoring catheter was placed in the femoral artery, and a central venous monitoring catheter was placed in the external carotid artery. RESULTS: Endotoxin (0.5 mg/kg, i.v.) was administered to cause shock. After this shock state was observed, the NOS inhibitors and catecholamines raised the blood pressure, and norepinephrine (NA, 2 microg/kg/h) was found to be more potent than S-methylisothiourea (SMT, 20 microg/kg/h). The combined effects of SMT-NA or SMT-DOB were greater than those of NA or dobutamine (DOB) alone. The histological changes induced by endotoxin shock were not ameliorated by the administration of NOS inhibitors but instead appeared to be exacerbated to some degree. CONCLUSION: NOS inhibitors combined with cathecholamines were thus suggested to be able to reduce the cathecolamine dosage in patients suffering from septic shock; They are thus considered to be hemodynamically effective agents.

Endoscopic hemostasis using fibrin adhesive to treat hemorrhage in the upper digestive system.

PURPOSE: There are several methods of achieving endoscopic hemostasis of hemorrhage in the upper digestive system. We compared the therapeutic results and advantages of using a local injection of fibrin adhesive for endoscopic hemostasis, which we have found more effective than other hemostatic methods. METHODS: Between October 2000 and April 2002, 16 patients with hemorrhage in the upper digestive system underwent endoscopic hemostasis using fibrin adhesive. The hemorrhage was caused by a hemorrhagic tendency from liver disease, anticoagulant therapy, or failed hemostasis with clipping or local ethanol injection. The fibrin adhesive was injected through a standard 21-gauge endoscopic needle using the so-called sandwich method. RESULTS: Hemostasis was successfully achieved by a single local injection of fibrin adhesive, in all except one patient who had been on anticoagulant therapy for a long time and needed an additional local injection of fibrin adhesive. CONCLUSION: Fibrin adhesive does not cause any tissue injury, and a sufficient amount can be injected endoscopically even in patients with liver dysfunction and those on anticoagulant therapy. Thus, we think that endoscopic hemostasis with fibrin adhesive is safe and effective.