We conducted a prospective observational study for investigating the changes in the 13th member of a disintegrin-like and metalloprotease with thrombospondin type 1 motif (ADAMTS13) and its ...association with the coagulofibrinolytic response in adult trauma patients.
In 39 trauma patients hospitalized for longer than 7 days, time-course changes in biomarkers of coagulofibrinolysis and systemic inflammation along with ADAMTS13 activity were examined. The patients were stratified into three groups based on ADAMTS13 activities on admission (day 0): normal group (≥70%), mildly decreased group (≥50 and < 70%) and moderately decreased group (< 50%).
Among 39 patients with a median Injury Severity Score (ISS) of 20, 11 patients developed disseminated intravascular coagulation (DIC) and 16 patients required transfusion. Six of 39 patients (15.4%) showed moderate decreased ADAMTS13 activity to < 50%, and 20 patients (51.3%) showed mild drops (≥50 and < 70%). These changes in ADAMTS13 activity on day 0 were significantly correlated with changes in IL-6 and other coagulofibrinolytic markers such as platelet counts, prothrombin time and fibrin/fibrinogen degradation product (FDP). Antithrombin activity (AT) and serum albumin (Alb) level showed significantly positive linear correlations with ADAMTS13 activity (AT: r = 0.513, p < 0.001; Alb: r = 0.647, p < 0.001). Simple logistic regression analyses showed that ADAMTS13 activity, if less than 50%, was significantly correlated with the development of DIC (OR 7.499, 95%CI 1.121-49.242, p = 0.038) and the need for transfusion of fresh frozen plasma (OR 9.000, 95%CI 1.327-61.025, p = 0.028).
ADAMTS13 activity decreased even in the early phase of trauma, which was complicated by coagulopathy and systemic inflammation. Furthermore, the decrease in ADAMTS13 activity was correlated with DIC and plasma transfusion.
An old sedative and hypnotic bromovalerylurea (BU) has anti-inflammatory effects. BU suppressed nitric oxide (NO) release and proinflammatory cytokine expression by lipopolysaccharide (LPS)-treated ...BV2 cells, a murine microglial cell line. However, BU did not inhibit LPS-induced nuclear translocation of nuclear factor-κB and subsequent transcription. BU suppressed LPS-induced phosphorylation of signal transducer and activator of transcription 1 (STAT1) and expression of interferon regulatory factor 1 (IRF1). The Janus kinase 1 (JAK1) inhibitor filgotinib suppressed the NO release much more weakly than that of BU, although filgotinib almost completely prevented LPS-induced STAT1 phosphorylation. Knockdown of JAK1, STAT1, or IRF1 did not affect the suppressive effects of BU on LPS-induced NO release by BV2 cells. A combination of BU and filgotinib synergistically suppressed the NO release. The mitochondrial complex I inhibitor rotenone, which did not prevent STAT1 phosphorylation or IRF1 expression, suppressed proinflammatory mediator expression less significantly than BU. BU and rotenone reduced intracellular ATP (iATP) levels to a similar extent. A combination of rotenone and filgotinib suppressed NO release by LPS-treated BV2 cells as strongly as BU. These results suggest that anti-inflammatory actions of BU may be attributable to the synergism of inhibition of JAK1/STAT1-dependent pathways and reduction in iATP level.
Sepsis is a pathology accompanied by increases in myeloid cells and decreases in lymphoid cells in circulation. In a murine sepsis model induced by cecum ligation and puncture (CLP), increasing ...numbers of neutrophils and decreasing levels of B-cells in circulation are among the earliest changes in the immune system. However, to date, the mechanisms for these changes remain to be elucidated. The study here sought to elucidate mechanisms underlying the changes in the leukocyte levels after CLP and also to determine what, if any, role for an involvement of the sympathetic nervous system (SNS). Here, male C57/BL6 mice were subjected to CLP or sham-CLP (abdominal wall incised, but cecum was not punctured). The changes in the number of circulating leukocytes over time were then investigated using flow cytometry. The results showed that a sham-CLP led to increased polymorphonuclear cells (PMN; most of which are neutrophils) and decreased B-cells in the circulation to an extent similar to that induced by CLP. Effects of adrenergic agonists and antagonists, as well as of adrenalectomy, were also examined in mice that underwent CLP or sham-CLP. Administering adrenaline or a β
2
adrenergic receptor agonist (clenbuterol) to mice 3 h before sacrifice produced almost identical changes to as what was seen 2 h after performing a sham-CLP. In contrast, giving a β
2
adrenergic receptor antagonist ICI118,551 1 h before a CLP or sham-CLP suppressed the expected changes 2 h after the operations. Noradrenaline and an α1 adrenergic receptor agonist phenylephrine did not exert significant effects. Adrenalectomy 24 h before a sham-CLP significantly abolished the expected sham-CLP-induced changes seen earlier. Clenbuterol increased splenocyte expression of Cxcr4 (a chemokine receptor gene); adrenalectomy abolished sham-CLP-induced Cxcr4 expression. A CXCR4 antagonist AMD3100 repressed the sham-CLP-induced changes. From these results, it may be concluded that sepsis-induced activation of the SNS may be one cause for immune dysfunction in sepsis - regardless of the pathogenetic processes.
We conducted a prospective observational study for investigating coagulofibrinolytic changes and mechanisms of antithrombin (AT) alternations in trauma.
Trauma patients hospitalized for more than ...seven days were analyzed for coagulofibrinolytic biomarkers. The patients were stratified into two groups according to AT activity level on admission (day 0), comprising normal AT and low AT patients.
Thirty-nine patients (median Injury Severity Score 20) exhibited initial coagulatory activation and triphasic fibrinolytic changes. AT activity did not show a negative linear correlation with levels of thrombin-antithrombin complex (TAT), a marker of coagulation activity and AT consumption, but was strongly correlated with levels of albumin (Alb), an index of vascular permeability, on day 0 (
= 0.702,
< 0.001). Furthermore, Alb was one of the independent predictors for AT on day 0. IL-6 on day 0 and thrombomodulin (TM) levels during the study period, reflecting systemic inflammation and endothelial cell injury, respectively, were significantly higher in the lower AT group (
= 10) than in the normal group (
= 29) (IL-6,
= 0.004; TM,
= 0.017). On days 2 and 4, TAT levels in the lower AT group were significantly higher than in the normal group.
Trauma caused clear triphasic coagulofibrinolytic changes. Decreased AT in the later phase might lead to a prolonged hypercoagulation. AT reduction in the initial phase of trauma is strongly associated with extravascular leakage as suggested by the association of Alb depletion with IL-6 and TM elevation, but not with AT consumption.
Heat stroke induces coagulofibrinolytic activation, which leads to life-threatening disseminated intravascular coagulation (DIC). However, treatment strategies for DIC in heat stroke have not yet ...been established, and also, the time course changes in coagulofibrinolytic markers have not been thoroughly evaluated. We report a severe heat stroke case with DIC who was eventually saved by anti-DIC treatments in accordance with changes in coagulofibrinolytic markers.
A 45-year-old man was found unconscious outside, and his body temperature was elevated to 41.9 °C. For heat stroke, we performed an immediate tracheal intubation under the general anesthesia along with cooling by iced gastric lavage, cold fluid administration, and an intravascular cooling using Thermogard™. About 4 h after admission, his core temperature fell to 37 °C. We assessed coagulofibrinolytic biomarkers and treated in accordance with changes in these parameters. This case exhibited a biphasic change varying from an enhanced to a suppressed fibrinolytic type of DIC depending on the relative balance between fibrinolytic activation and the level of plasminogen activator inhibitor-1 (PAI-1). In the early phase with consumption coagulopathy and enhanced fibrinolysis, we transfused a large amount of fresh frozen plasma (FFP) and platelets with tranexamic acid, an antifibrinolytic agent, possibly providing relief for the bleeding tendency. Anticoagulant therapy using recombinant human thrombomodulin-α (rh-TM-α) and antithrombin III (ATIII) concentrate was especially effective for DIC with a suppressed fibrinolytic phenotype in the later phase, after which organ failure that included severe hepatic failure was remarkably improved.
The present case may indicate the clinical significance of monitoring coagulifibrinolytic changes and the potential benefits of anticoagulants for heat stroke-induced DIC.
Sepsis is a severe pathologic event, frequently causing death in critically ill patients. However, there are no approved drugs to treat sepsis, despite clinical trials of many agents that have ...distinct targets. Therefore, a novel effective treatment should be developed based on the pathogenesis of sepsis. We recently observed that an old hypnotic drug, bromvalerylurea (BU) suppressed expression of many kinds of pro- and anti-inflammatory mediators in LPS- or interferon-γ activated alveolar and peritoneal macrophages (AMs and PMs). Taken the anti-inflammatory effects of BU on macrophages, we challenged it to septic rats that had been subjected to cecum-ligation and puncture (CLP). BU was subcutaneously administered to septic rats twice per day. Seven days after CLP treatment, 85% of septic rats administrated vehicle had died, whereas administration of BU reduce the rate to 50%. Septic rats showed symptoms of multi-organ failure; respiratory, circulatory and renal system failures as revealed by histopathological analyses, blood gas test and others. BU ameliorated these symptoms. BU also prevented elevated serum-IL-6 level as well as IL-6 mRNA expression in septic rats. Collectively, BU might be a novel agent to ameliorate sepsis by preventing the onset of MOF.
•A hypnotic bromvalerylurea suppressed proinflammatory activation of LPS-treated macrophages.•Bromvalerylurea suppressed LPS- and interferon-γ-induced STAT1 phosphorylation.•Bromvalerylurea increased survival of a cecum-ligation and puncture-induced sepsis rat model.•Bromvalerylurea ameliorated multi-organ failure accompanied with sepsis.
Purpose
Screw fixation for unstable pelvic ring fractures is generally performed using the C-arm. However, some studies reported erroneous piercing with screws, nerve injuries, and vessel injuries. ...Recent studies have reported the efficacy of screw fixations using navigation systems. The purpose of this retrospective study was to investigate the accuracy of screw fixation using the O-arm
®
imaging system and StealthStation
®
navigation system for unstable pelvic ring fractures.
Methods
The participants were 10 patients with unstable pelvic ring fractures, who underwent screw fixations using the O-arm StealthStation navigation system (nine cases with iliosacral screw and one case with lateral compression screw). We investigated operation duration, bleeding during operation, the presence of complications during operation, and the presence of cortical bone perforation by the screws based on postoperative CT scan images. We also measured the difference in screw tip positions between intraoperative navigation screen shot images and postoperative CT scan images.
Results
The average operation duration was 71 min, average bleeding was 12 ml, and there were no nerve or vessel injuries during the operation. There was no cortical bone perforation by the screws. The average difference between intraoperative navigation images and postoperative CT images was 2.5 ± 0.9 mm, for all 18 screws used in this study.
Conclusion
Our results suggest that the O-arm StealthStation navigation system provides accurate screw fixation for unstable pelvic ring fractures.
Background Reports regarding arthroscopic fixation of the osteochondral fragments for elbow osteochondritis dissecans (OCD) are few. This study assessed the clinical outcomes of arthroscopic fixation ...of unstable osteochondral fragments by using absorbable pins over a postoperative period of at least 1 year. Methods The patients were 13 adolescent baseball players with a mean age of 14 years (range, 12-16 years) who underwent OCD of primary lesions at International Cartilage Repair Society grades III and IV. The patients were evaluated by using validated outcome measures at a mean follow-up period of 24 months (range, 12-50 months). Results The mean (standard deviation) score in the disability/symptom section of the Disabilities of the Arm, Shoulder, and Hand improved from 12.4 (6.0) before the surgery to 0.5 (1.2) after the surgery, and the sports section improved from 74.5 (25.4) to 1.4 (5.2). The mean (standard deviation) extension improved from −11° (10.8) to −2° (3.9; P < .001). The mean (SD) flexion improved from 129° (11.6) to 137° (5.6; P = .040). All patients were able to resume playing baseball, and 9 (69%) resumed playing at the same position as before their injuries. Conclusions The clinical results of arthroscopic osteochondral fragment fixation in the teenaged baseball players with elbow OCD, albeit obtained over only a short period, were favorable. This arthroscopic treatment enables repair of lesions and is considered appropriate for unstable OCD during the adolescent growth spurt.
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