Effectiveness and Usage Trends of Hemorrhage Control Interventions in Patients with Pelvic Fracture in Shock.

BACKGROUND: Hemorrhage control for pelvic fractures remains challenging. There are several kinds of hemostatic interventions, including angiography/angioembolization (AG/AE), external fixation (EF), and resuscitative endovascular balloon occlusion of the aorta (REBOA). However, no large studies have been conducted for the comparative review of each intervention. In this study, we examined the usage trend of therapeutic interventions in Japan for patients with pelvic fractures in shock and the influence of these interventions on mortality. METHODS: Data of adult patients with pelvic fracture who were in shock were obtained from the Japanese Trauma Data Bank (2004-2014). The primary endpoint was the influence of each intervention (AG/AE, EF, and REBOA) on in-hospital mortality. We also investigated the frequency of each intervention. RESULTS: A total of 3149 patients met all our inclusion criteria. Specifically, 1131 (35.9%), 496 (15.8%), and 256 (8.1%) patients underwent AG, EF, and REBOA interventions, respectively. Therapeutic AE was performed in 690 patients who underwent AG (61.0%). The overall mortality rate was 31.4%. Multiple regression analysis identified that AG/AE (OR 0.64, 95% CI 0.52-0.80) and EF (OR 0.75, 95% CI 0.58-0.98) were significantly associated with survival, whereas REBOA (OR 4.17, 95% CI 3.00-5.82) was significantly associated with worse outcomes. CONCLUSIONS: In Japan, patients with pelvic fracture who were in shock had high mortality rates. AG/AE and EF were associated with decreased mortality. AG may benefit from the early detection of arterial bleeding, leading to decreased mortality of patients with pelvic fracture in shock.

Passive cigarette smoking changes the circadian rhythm of clock genes in rat intervertebral discs.

We aimed to elucidate the molecular changes in intervertebral discs (IVDs) caused by passive smoking. Rats were subjected to 8 weeks of passive smoking; thereafter, their lumbar vertebrae were harvested. The annulus fibrosus and cartilage endplate (AF/CEP) were harvested together, and the nucleus pulposus (NP) was isolated separately. The expression of 27,342 rat genes was analyzed. In 3 "nonsmoking" rats, 96 of 112 genes whose expression varied ≥10-fold between the AF/CEP and NP were more highly expressed in the AF/CEP. With these differentially expressed genes, we uncovered novel AF/CEP and NP marker genes and indicated their possible novel functions. Although passive smoking induced less marked alteration in the gene expression profiles of both the AF/CEP and NP, multiple clock-related genes showed altered expression. These genes were expressed with a circadian rhythm in IVD cells, and most genes showed a phase shift of -6 to -9 h induced by passive smoking. Some clock-related genes showed abolished oscillation in the NP. Passive smoking also changed the expression levels of proteases and protease inhibitors and reduced the expression of NP marker genes. Thus, passive smoking induces changes in the circadian rhythm of a peripheral clock (IVD clock) that might be involved in molecular events related to IVD degeneration.

Identification of the actinorhodin monomer and its related compound from a deletion mutant of the actVA-ORF4 gene of Streptomyces coelicolor A3(2).

An oxygenated derivative of dihydrokalafungin (DHK) was isolated from a deletion mutant of the actVA-ORF4 gene involved in the biosynthesis of a dimeric benzoisochromanequinone (BIQ) antibiotic, actinorhodin (ACT), in Streptomyces coelicolor A3(2). Spectroscopic analysis elucidated its structure as 8-hydroxy-DHK, corresponding to the monomeric unit of ACT. Further metabolite analysis identified its related compound, clearly derived from the reduction of 8-hydroxy-DHK. The structures of these metabolites indicate the essential role of ActVA-ORF4 in ACT biosynthesis, specifically in dimerization of a BIQ intermediate via C-C bond formation.

Inhibition of lipopolysaccharide stimulated interleukin-1beta production after subarachnoid hemorrhage.

PURPOSE: To identify the characteristics of cytokine production from peripheral blood mononuclear cells (PBMCs) in response to lipopolysaccharide (LPS) in patients with subarachnoid hemorrhage (SAH). METHODS: Blood samples were collected on the first day and 3 days after SAH (n = 12) to measure plasma concentrations of catecholamines, tumor necrosis factor-alpha (TNF-alpha), interleukin (IL)-1beta and IL-10. PBMCs from SAH patients or healthy volunteers were incubated with LPS (1 microg) for 24 hours. In the second phase, PBMCs from healthy volunteers (n = 6) were incubated with or without catecholamine (10 micromol/1) for 6 hours. After pre-treatment, the cells were treated with LPS (1 microg) for 18 hours. Supernatants were extracted and subjected to measurement by enzyme-linked immunosorbent assay. RESULTS: Plasma concentrations of epinephrine or dopamine prolong increased significantly 3 days after SAH, involved in elevation of plasma IL-10. In the PBMCs from the SAH patients, LPS-stimulated IL- 10 production was inhibited significantly. Pre-treatment with epinephrine or dopamine inhibited LPS-stimulated IL-1beta production significantly in the PBMCs from the healthy volunteers. CONCLUSIONS: The initial SAH involved in an impaired production of pro-inflammatory cytokines in response to LPS with an elevation of plasma epinephrine, dopamine and IL-10 after acute stressful conditions. This phenomenon may play an important role of an early immnosupression in patients with poor grade SAH.

Reduced effectiveness of hypothermia in patients lacking the wave V in auditory brainstem responses immediately following resuscitation from cardiac arrest.

AIMS: Therapeutic hypothermia appears to improve the outcome of pre-hospital cardio-pulmonary arrest (CPA) in patients with an initial cardiac rhythm of ventricular fibrillation or nonperfusing ventricular tachycardia (VF/VT). Notwithstanding, the outcome of this procedure is certainly difficult to predict based solely on the initial rhythm. The aim of the present study was to predict the outcome using auditory brainstem responses (ABRs) in CPA patients treated with therapeutic hypothermia. DESIGN AND SETTING: A prospective observational study in the intensive care unit of a university hospital. PATIENTS: The study included 26 patients resuscitated from out-of-hospital CPA. INTERVENTIONS: Basic and advanced cardiac life support, intensive care and post-resuscitative hypothermia. MEASUREMENT AND RESULTS: ABRs were recorded immediately after the return of spontaneous circulation (ROSC). An ABR wave V was recorded in 16 patients. Among 8 patients with a favourable outcome, the initial rhythms were VF/VT in 6 patients and other rhythms in 2. All 10 patients without a detectable ABR wave V had an unfavourable outcome. The VF/VT as the initial arrest rhythm and the presence of wave V were significantly (p = 0.0095) correlated with a favourable outcome. The presence of wave V had a 100% sensitivity to a favourable outcome. CONCLUSION: The absence of the ABR wave V in the early phase after ROSC wave indicated a reduced effect of therapeutic hypothermia, even in cases that underwent hypothermia promptly after out-of-hospital CPA. Measurement of ABRs appears to be useful as a predictor of effectiveness and as a criterion for determining the indication for therapeutic hypothermia.