Targeted Temperature Management for Traumatic Asphyxia: A Case Report.

Traumatic asphyxia (TA) is a rare condition due to severe crush injury to the upper abdomen or chest region. Elevated intrathoracic pressure causes impaired venous return, which damages the small vessels. Consciousness is reportedly lost in many TA cases. In the most severe cases, hypoxic encephalopathy occurs. Since TA patients usually have other traumatic complications such as thoracic or abdominal injury, the mortality rate of this syndrome is quite variable. Hypothermia is a risk factor for mortality in trauma patients, and targeted temperature management (TTM) is rarely performed for trauma cases. There are scattered articles reporting the usefulness of TTM in severe traumatic brain injury. To our best knowledge, there have been no reports of TTM in TA cases. We herein report a TA case with decorticate rigidity having a good neurological outcome after TTM.

Low-dose immunoglobulin G is not associated with mortality in patients with sepsis and septic shock.

BACKGROUND: The administration of low-dose intravenous immunoglobulin G (IVIgG) (5 g/day for 3 days; approximate total 0.3 g/kg) is widely used as an adjunctive treatment for patients with sepsis in Japan, but its efficacy in the reduction of mortality has not been evaluated. We investigated whether the administration of low-dose IVIgG is associated with clinically important outcomes including intensive care unit (ICU) and in-hospital mortality. METHODS: This is a post-hoc subgroup analysis of data from a retrospective cohort study, the Japan Septic Disseminated Intravascular Coagulation (JSEPTIC DIC) study. The JSEPTIC DIC study was conducted in 42 ICUs in 40 institutions throughout Japan, and it investigated associations between sepsis-related coagulopathy, anticoagulation therapies, and clinical outcomes of 3195 adult patients with sepsis and septic shock admitted to ICUs from January 2011 through December 2013. To investigate associations between low-dose IVIgG administration and mortalities, propensity score-based matching analysis was used. RESULTS: IVIgG was administered to 960 patients (30.8%). Patients who received IVIgG were more severely ill than those who did not (Acute Physiology and Chronic Health Evaluation (APACHE) II score 24.2 ± 8.8 vs 22.6 ± 8.7, p < 0.001). They had higher ICU mortality (22.8% vs 17.4%, p < 0.001), but similar in-hospital mortality (34.4% vs 31.0%, p = 0.066). In propensity score-matched analysis, 653 pairs were created. Both ICU mortality and in-hospital mortality were similar between the two groups (21.0% vs 18.1%, p = 0.185, and 32.9% vs 28.6%, p = 0.093, respectively) using generalized estimating equations fitted with logistic regression models adjusted for other therapeutic interventions. The administration of IVIgG was not associated with ICU or in-hospital mortality (odds ratio (OR) 0.883; 95% confidence interval (CI) 0.655-1.192, p = 0.417, and OR 0.957, 95% CI, 0.724-1.265, p = 0.758, respectively). CONCLUSIONS: In this analysis of a large cohort of patients with sepsis and septic shock, the administration of low-dose IVIgG as an adjunctive therapy was not associated with a decrease in ICU or in-hospital mortality. TRIAL REGISTRATION: University Hospital Medical Information Network Individual Clinical Trials Registry, UMIN-CTR000012543 . Registered on 10 December 2013.

Antithrombin Supplementation and Mortality in Sepsis-Induced Disseminated Intravascular Coagulation: A Multicenter Retrospective Observational Study.

Supplemental doses of antithrombin (AT) are widely used to treat sepsis-induced disseminated intravascular coagulation (DIC) in Japan. However, evidence on the benefits of AT supplementation for DIC is insufficient. This multicenter retrospective observational study aimed to clarify the effect of AT supplementation on sepsis-induced DIC using propensity score analyses. Data from 3,195 consecutive adult patients admitted to 42 intensive care units for severe sepsis treatment were retrospectively analyzed; 1,784 patients were diagnosed with DIC (n = 715, AT group; n = 1,069, control group). Inverse probability of treatment-weighted propensity score analysis indicated a statistically significant association between AT supplementation and lower in-hospital all-cause mortality (n = 1,784, odds ratio [95% confidence intervals]: 0.748 [0.572-0.978], P = 0.034). However, quintile-stratified propensity score analysis (n = 1,784, odds ratio: 0.823 [0.646-1.050], P = 0.117) and propensity score matching analysis (461 matching pairs, odds ratio: 0.855 [0.649-1.125], P = 0.263) did not show this association. In the early days after intensive care unit admission, the survival rate was statistically higher in the propensity score-matched AT group than in the propensity score-matched control group (P = 0.007). In DIC patients without concomitant heparin administration, similar results were observed. In conclusion, AT supplementation may be associated with reduced in-hospital all-cause mortality in patients with sepsis-induced DIC. However, the statistical robustness of this connection was not strong. In addition, although the number of transfusions needed in patients with AT supplementation increased, severe bleeding complications did not.

Characteristics, treatments, and outcomes of severe sepsis of 3195 ICU-treated adult patients throughout Japan during 2011-2013.

Severe sepsis is a major concern in the intensive care unit (ICU), although there is very little epidemiological information regarding severe sepsis in Japan. This study evaluated 3195 patients with severe sepsis in 42 ICUs throughout Japan. The patients with severe sepsis had a mean age of 70 ± 15 years and a mean Acute Physiology and Chronic Health Evaluation II score of 23 ± 9. The estimated survival rates at 28 and 90 days after ICU admission were 73.6 and 56.3 %, respectively.

Regional cerebral oxygen saturation monitoring for predicting interventional outcomes in patients following out-of-hospital cardiac arrest of presumed cardiac cause: A prospective, observational, multicentre study.

AIM: This study investigated the value of regional cerebral oxygen saturation (rSO2) monitoring upon arrival at the hospital for predicting post-cardiac arrest intervention outcomes. METHODS: We enrolled 1195 patients with out-of-hospital cardiac arrest of presumed cardiac cause from the Japan-Prediction of Neurological Outcomes in Patients Post-cardiac Arrest Registry. The primary endpoint was a good neurologic outcome (cerebral performance categories 1 or 2 [CPC1/2]) 90 days post-event. RESULTS: A total of 68 patients (6%) had good neurologic outcomes. We found a mean rSO2 of 21%±13%. A receiver operating characteristic curve analysis indicated an optimal rSO2 cut-off of ≥40% for good neurologic outcomes (area under the curve 0.92, sensitivity 0.81, specificity 0.96). Good neurologic outcomes were observed in 53% (55/103) and 1% (13/1092) of patients with high (≥40%) and low (<40%) rSO2, respectively. Even without return of spontaneous circulation (ROSC) upon arrival at the hospital, 30% (9/30) of patients with high rSO2 had good neurologic outcomes. Furthermore, 16 patients demonstrating ROSC upon arrival at the hospital and low rSO2 had poor neurologic outcomes. Multivariate analyses indicated that high rSO2 was independently associated with good neurologic outcomes (odds ratio=14.07, P<0.001). Patients with high rSO2 showed favourable neurologic prognoses if they had undergone therapeutic hypothermia or coronary angiography (CPC1/2, 69% [54/78]). However, 24% (25/103) of those with high rSO2 did not undergo these procedures and exhibited unfavourable neurologic prognoses (CPC1/2, 4% [1/25]). CONCLUSION: rSO2 is a good indicator of 90-day neurologic outcomes for post-cardiac arrest intervention patients.

Characteristics of regional cerebral oxygen saturation levels in patients with out-of-hospital cardiac arrest with or without return of spontaneous circulation: A prospective observational multicentre study.

AIM: Our study aimed at filling the fundamental knowledge gap on the characteristics of regional brain oxygen saturation (rSO2) levels in out-of-hospital cardiac arrest (OHCA) patients with or without return of spontaneous circulation (ROSC) upon arrival at the hospital for estimating the quality of cardiopulmonary resuscitation and neurological prognostication in these patients. METHODS: We enrolled 1921 OHCA patients from the Japan - Prediction of Neurological Outcomes in Patients Post-cardiac Arrest Registry and measured their rSO2 immediately upon arrival at the hospital by near-infrared spectroscopy using two independent forehead probes (right and left). We also assessed the percentage of patients with a good neurological outcome (defined as cerebral performance categories 1 or 2) 90 days post cardiac arrest. RESULTS: After 90 days, 79 (4%) patients had good neurological outcomes and a median lower rSO2 level of 15% (15-20%). Compared to patients without ROSC upon arrival at the hospital, those with ROSC had significantly higher rSO2 levels (56% [39-65%] vs. 15% [15-17%], respectively; P<0.01), and significantly correlated right- and left-sided regional brain oxygen saturation levels (R=0.94 vs. 0.66, respectively). In both groups, the percentage of patients with a good 90-day neurological outcome increased significantly in proportion to their rSO2 levels upon arrival at the hospital (P<0.01). CONCLUSION: Our data indicate that measuring rSO2 levels might be effective for both monitoring the quality of resuscitation and neurological prognostication in patients with OHCA.

Development of an intracellularly acting inhibitory peptide selective for PKN.

PKNs form a subfamily of the AGC serine/threonine protein kinases, and have a catalytic domain homologous with that of PKC (protein kinase C) in the C-terminal region and three characteristic ACC (antiparallel coiled-coil) domain repeats in the N-terminal region. The preferred peptide phosphorylation motif for PKNs determined by a combinatorial peptide library method was highly similar to that of PKCs within a 10-amino-acid stretch. Previously reported PKN inhibitory compounds also inhibit PKCs to a similar extent, and no PKN selective inhibitors have been commercially available. We have identified a 15-amino-acid peptide inhibitor of PKNs based on amino acids 485-499 of the C-terminal region of the C2-like domain of PKN1. This peptide, designated as PRL, selectively inhibits the kinase activity of all isoforms of PKN (Ki=0.7 muM) towards a peptide substrate, as well as autophosphorylation activity of PKN in vitro, in contrast with PKC. Reversible conjugation by a disulfide bond of a carrier peptide bearing a penetration accelerating sequence to PRL, facilitated the cellular uptake of this peptide and significantly inhibited phosphorylation of tau by PKN1 at the PKN1-specific phosphorylation site in vivo. This peptide may serve as a valuable tool for investigating PKN activation and PKN-mediated responses.