中田 孝明

Background and purpose: The Japanese Clinical Practice Guidelines for Management of Sepsis and Septic Shock 2016 (J-SSCG 2016), a Japanese-specific set of clinical practice guidelines for sepsis and septic shock created jointly by the Japanese Society of Intensive Care Medicine and the Japanese Association for Acute Medicine, was first released in February 2017 and published in the Journal of JSICM, [2017; Volume 24 (supplement 2)] 10.3918/jsicm.24S0001 and Journal of Japanese Association for Acute Medicine [2017; Volume 28, (supplement 1)] http://onlinelibrary.wiley.com/doi/10.1002/jja2.2017.28.issue-S1/issuetoc.This abridged English edition of the J-SSCG 2016 was produced with permission from the Japanese Association of Acute Medicine and the Japanese Society for Intensive Care Medicine. Methods: Members of the Japanese Society of Intensive Care Medicine and the Japanese Association for Acute Medicine were selected and organized into 19 committee members and 52 working group members. The guidelines were prepared in accordance with the Medical Information Network Distribution Service (Minds) creation procedures. The Academic Guidelines Promotion Team was organized to oversee and provide academic support to the respective activities allocated to each Guideline Creation Team. To improve quality assurance and workflow transparency, a mutual peer review system was established, and discussions within each team were open to the public. Public comments were collected once after the initial formulation of a clinical question (CQ) and twice during the review of the final draft. Recommendations were determined to have been adopted after obtaining support from a two-thirds (> 66.6%) majority vote of each of the 19 committee members. Results: A total of 87 CQs were selected among 19 clinical areas, including pediatric topics and several other important areas not covered in the first edition of the Japanese guidelines (J-SSCG 2012). The approval rate obtained through committee voting, in addition to ratings of the strengths of the recommendation, and its supporting evidence were also added to each recommendation statement. We conducted meta-analyses for 29 CQs. Thirty-seven CQs contained recommendations in the form of an expert consensus due to insufficient evidence. No recommendations were provided for five CQs. Conclusions: Based on the evidence gathered, we were able to formulate Japanese-specific clinical practice guidelines that are tailored to the Japanese context in a highly transparent manner. These guidelines can easily be used not only by specialists, but also by non-specialists, general clinicians, nurses, pharmacists, clinical engineers, and other healthcare professionals.

Background and Purpose: The Japanese Clinical Practice Guidelines for Management of Sepsis and Septic Shock 2016 (J-SSCG 2016), a Japanese-specific set of clinical practice guidelines for sepsis and septic shock created jointly by the Japanese Society of Intensive Care Medicine and the Japanese Association for Acute Medicine, was first released in February 2017 in Japanese. An English-language version of these guidelines was created based on the contents of the original Japanese-language version. Methods: Members of the Japanese Society of Intensive Care Medicine and the Japanese Association for Acute Medicine were selected and organized into 19 committee members and 52 working group members. The guidelines were prepared in accordance with the Medical Information Network Distribution Service (Minds) creation procedures. The Academic Guidelines Promotion Team was organized to oversee and provide academic support to the respective activities allocated to each Guideline Creation Team. To improve quality assurance and workflow transparency, a mutual peer review system was established, and discussions within each team were open to the public. Public comments were collected once after the initial formulation of a clinical question (CQ), and twice during the review of the final draft. Recommendations were determined to have been adopted after obtaining support from a two-thirds (>66.6%) majority vote of each of the 19 committee members. Results: A total of 87 CQs were selected among 19 clinical areas, including pediatric topics and several other important areas not covered in the first edition of the Japanese guidelines (J-SSCG 2012). The approval rate obtained through committee voting, in addition to ratings of the strengths of the recommendation and its supporting evidence were also added to each recommendation statement. We conducted meta-analyses for 29 CQs. Thirty seven CQs contained recommendations in the form of an expert consensus due to insufficient evidence. No recommendations were provided for 5 CQs. Conclusions: Based on the evidence gathered, we were able to formulate Japanese-specific clinical practice guidelines that are tailored to the Japanese context in a highly transparent manner. These guidelines can easily be used not only by specialists, but also by non-specialists, general clinicians, nurses, pharmacists, clinical engineers, and other healthcare professionals.

Background: The ability of blood levels of interleukin (IL)-6 to differentiate between infection and non-infection in critically ill patients with suspected infection is unclear. We assessed the diagnostic accuracy of serum IL-6 levels for the diagnosis of infection in critically ill patients. Methods: We systematically searched the PubMed, MEDLINE, Cochrane Resister of Controlled Trials, Cochrane Database of Systematic Reviews, CINAHL, and Igaku Chuo Zasshi databases for studies published from 1986 to August 2016 that evaluated the accuracy of IL-6 levels for the diagnosis of infection. We constructed 2 × 2 tables and calculated summary estimates of sensitivity and specificity using a bivariate random-effects model. Results: The literature search identified 775 articles, six of which with a total of 527 patients were included according to the predefined criteria. The pooled sensitivity, specificity, and diagnostic odds ratio were 0.73 (95% confidence interval [CI], 0.61–0.82), 0.76 (95% CI, 0.61–0.87), and 2.31 (95% CI, 1.20–3.48), respectively. The area under the curve (AUC) of the summary receiver operator characteristic (SROC) curve was 0.81 (95% CI, 0.78–0.85). In the secondary analysis of two studies with a total of 263 adult critically ill patients with organ dysfunction, the pooled sensitivity, specificity, and diagnostic odds ratio were 0.81 (95% CI, 0.75–0.86), 0.77 (95% CI, 0.67–0.84), and 2.87 (95% CI 2.15–3.60), respectively. Conclusions: Blood levels of IL-6 have a moderate diagnostic value and a potential clinical utility to differentiate infection in critically ill patients with suspected infection.

Blood purification therapy using hemofilters with high adsorbing capabilities has been reported to remove excessive humoral mediators from the blood of patients with sepsis. However, there are insufficient studies of the adsorbates bound to hemofilter membranes. We hypothesized that these adsorbates in acute kidney injury (AKI) patients with sepsis were different from those in patients without sepsis and that proteome analysis of the adsorbates would identify novel substances of sepsis. This study included 20 patients who had AKI upon admission to intensive care units (ICUs) and who received continuous renal replacement therapy using polymethyl methacrylate hemofilters. We isolated adsorbates from the hemofilters after use and performed comprehensive proteome analysis. A total of 429 proteins were identified in these adsorbates. Adsorbates from the hemofilters of patients with sepsis had significantly increased frequency of proteins associated with "immune system process" and "biological adhesion" functions compared to those of non-sepsis patients (P < 0.05). Of 429 proteins, 197 were identified only in sepsis adsorbates. Of these, 3 proteins including carbonic anhydrase 1 (CA1) and leucine-rich alpha-2-glycoprotein (LRG1) were identified in all samples from sepsis patients and have not been previously reported in sepsis patients. Validation analysis of patient serum revealed that patients with sepsis had increased serum levels of CA1 and LRG1 compared to patients without sepsis (P < 0.05). To conclude, there were significant differences in the characteristics of the adsorbates from sepsis and non-sepsis patients. CA1 and LRG1 appear to be novel substances associated with sepsis.

Patients receiving extracorporeal membrane oxygenation (ECMO) often require continuous renal replacement therapy (CRRT). The intra-circuit pressure of adult ECMO usually deviates from the physiological range. We investigated the use of CRRT connected to an ECMO circuit with physiological intra-circuit pressures (0-150 mmHg, defined as the "safety range") using an in vitro experiment involving a water-filled ECMO circuit. The intra-circuit pressure pre-pump, post-pump, and post-oxygenator were measured while varying the height of the pump or ECMO flow. The bypass conduit pressure and distance from the post-oxygenator port were measured to find the "safety point", where the bypass pressure remained within the safety range. Both drainage and return limbs of the CRRT machine were connected to the safety point and the inlet and outlet pressures of the hemofilter were recorded while varying the ECMO and CRRT flow. The pre-pump pressure only remained within the safety range for heights >75 cm (ECMO flow = 4 L/min) or ECMO flow <3.5 L min (height = 50 cm). The post-pump and post-oxygenator pressure was generally outside of the safety range. The bypass pressure decreased according to the distance from the post-oxygenator port and the safety point was found at 60 or 75 cm (in a 90-cm length conduit) regardless of ECMO flow. The hemofilter inlet and outlet pressures remained within the safety range for all conditions of ECMO and CRRT flow, findings validated in clinical cases. The bypass conduit within an ECMO circuit can be connected to a CRRT machine safely under physiological pressures in adult patients receiving ECMO.

2012年に日本集中治療医学会が発表した日本版敗血症診療ガイドラインの改訂に際し、日本集中治療医学会と日本救急医学会合同の特別委員会が組織された。単なる改訂版の位置づけではなく、一般臨床家にも理解しやすく、かつ質の高いガイドラインとすることで、広い普及を目指した。いくつかの注目すべき領域と小児領域を新たに追加し、計19領域、89に及ぶ臨床課題[クリニカルクエスチョン(clinical question、CQ)]を網羅した。大規模ガイドラインであることや、この領域における本邦の実情を鑑みて組織編成を行い、中立的な立場で横断的に活躍するアカデミックガイドライン推進班を組織した。質の担保と作業過程の透明化を図るための様々な工夫を行い、パブリックコメントの募集は計3回行った。さらに、将来への橋渡しとなることを企図して、多くの若手医師をメンバーに登用した。当初の狙い通り、学会や施設の垣根を越えたネットワーク構築が進み、これを基盤に、ガイドラインとは独立して多施設研究や独自のシステマティックレビューを行い論文化するなどの動きが生まれ、今なお活発となっている。また、敗血症診療を広くカバーする意味でも、両学会が協力して作成した意義は大きい。本ガイドラインがベースとなり、救急・集中治療領域における本邦からのエビデンス発信のプラットフォームが形成されることを願ってやまない。なお、本ガイドラインは、日本集中治療医学会と日本救急医学会の両機関誌のガイドライン増刊号として同時掲載するものである。(著者抄録)

Background: A sudden shortage of physician resources due to overwhelming patient needs can affect the quality of care in the emergency department (ED). Developing effective response strategies remains a challenging research area. We created a novel system using information and communication technology (ICT) to respond to a sudden shortage, and tested the system to determine whether it would compensate for a shortage. Methods: Patients (n = 4890) transferred to a level I trauma center in Japan during 2012-2015 were studied. We assessed whether the system secured the necessary physicians without using other means such as phone or pager, and calculated fulfillment rate by the system as a primary outcome variable. We tested for the difference in probability of multiple casualties among total casualties transferred to the ED as an indicator of ability to respond to excessive patient needs, in a secondary analysis before and after system introduction. Results: The system was activated 24 times (stand-by request [n = 12], attendance request [n = 12]) in 24 months, and secured the necessary physicians without using other means; fulfillment rate was 100%. There was no significant difference in the probability of multiple casualties during daytime weekdays hours before and after system introduction, while the probability of multiple casualties during night or weekend hours after system introduction significantly increased compared to before system introduction (4.8% vs. 12.9%, P < 0.0001). On the whole, the probability of multiple casualties increased more than 2 times after system introduction 6.2% vs. 13.6%, P < 0.0001). Discussion: After introducing the system, probability of multiple casualties increased. Thus the system may contribute to improvement in the ability to respond to sudden excessive patient needs in multiple causalities. Conclusions: A novel system using ICT successfully secured immediate responses from needed physicians outside the hospital without increasing user workload, and increased the ability to respond to excessive patient needs. The system appears to be able to compensate for a shortage of physician in the ED due to excessive patient transfers, particularly during off-hours.

Purpose The medical emergency team (MET) can be activated anytime and anywhere in a hospital. We hypothesized the timing and location of MET activation are associated with seriousness of outcome. Materials and Methods We tested for an association of clinical outcomes with timing and location using a university hospital cohort in Japan (n = 328). The primary outcome was short-term serious outcome (unplanned ICU admission after MET activation or death at scene). Results Patients for whom the MET was activated in the evening or night-time had significantly higher rates of short-term serious outcome than those for whom it was activated during the daytime (vs. evening: adjusted OR = 2. 53, 95% CI = 1.24-5.13, P = 0.010; night-time: adjusted OR = 2.45, 95% CI = 1.09-5.50, P = 0.030). Patients for whom the MET was activated in public space had decreased short-term serious outcome compared to medical spaces (public space: adjusted OR = 0.19, 95% CI = 0.07-0.54, P = 0.0017). Night-time (vs. daytime) and medical space (vs. public space) were significantly associated with higher risks of unexpected cardiac arrest and 28-day mortality. Conclusions Patients for whom the MET was activated in the evening/night-time, or in medical space, had a higher rate of short-term serious outcomes. Taking measures against these risk factors may improve MET performance.

Introduction: There are significant unmet requirements for rapid differential diagnosis of infection in patients admitted to intensive care units. Serum levels of interleukin-6 (IL-6), procalcitonin (PCT), presepsin, and C-reactive protein (CRP) are measured in clinical practice; however, their clinical utility in patients with organ dysfunction has not been tested adequately. Thus, we investigated the diagnostic and prognostic value of IL-6, PCT, presepsin, and CRP in critically ill patients who had organ dysfunction with suspicion of infection. Methods: In 100 consecutive critically ill patients with organ dysfunction and suspected infection, serum levels of IL-6, PCT, presepsin, and CRP were measured upon suspicion of infection and serially every other day up to 7 days (cohort 1). The primary outcome variable was the presence of infections. The diagnostic value of IL-6 was further tested in cohort 2 (n = 72, case-control matched). The secondary outcome variables were the sequential organ failure assessment (SOFA) score, serum creatinine levels, and 28-day mortality. Results: Among the four biomarkers, serum IL-6 levels had the highest area under the curve (AUC) value of 0.824 (95% confidence interval [CI] 0.735-0.913) for diagnosing infection in critically ill patients with organ dysfunction and suspected infection in cohort 1 (AUC [95% CI] for the other biomarkers: PCT, 0.813 [0.714-0.911]; CRP, 0.764 [0.645-0.883]; presepsin, 0.681 [0.513-0.849]). In cohort 2, the sensitivity and specificity of IL-6 for diagnosing infection were 0.861 and 0.806, respectively. The presepsin levels were significantly correlated with the SOFA score and serum creatinine levels upon suspicion of infection (r > 0.5), especially serum creatinine levels in the patients without infection (r = 0.789). Serum IL-6 levels were significant predictors of 28-day mortality. The AUC value of serum IL-6 levels for 28-day mortality increased over time; the serum IL-6 levels on Day 7 had the highest AUC value of 0.883 (95% CI, 0.788-0.978) for 28-day mortality. Conclusion: Among serum IL-6, PCT, presepsin, and CRP levels, serum IL-6 levels had the highest diagnostic value for infection. They were also significant predictors of 28-day mortality. Hence, they may improve diagnosis of infection and prediction of 28-day mortality in critically ill patients with organ dysfunction.

Streptococcal toxic shock syndrome (STSS), an invasive Streptococcus pyogenes (Group A streptococcus) infection with hypotension and multiple organ failure, is quite rare in pregnancy but is characterized by rapid disease progression and high fatality rates. We present a case of STSS with infection-induced cardiac dysfunction in a pregnant woman who was treated with veno-arterial extracorporeal membrane oxygenation (VA-ECMO). A 24-year-old multiparous woman in the third trimester had early symptoms of high fever and diarrhea 1 day prior to admission to the hospital emergency department. On admission, she had multiple organ failure including circulatory failure. Due to fetal distress, emergency Cesarean section was carried out and transferred to intensive care units. She had refractory circulatory failure with depressed myocardial contractility with progressive multiple organ failure, despite receiving significant hemodynamic supports including high-dose catecholamine. Thus, VA-ECMO was initiated 18 h after intensive care unit admission. Consequently, ECMO provided extra time to recover from infection and myocardial depression. She was successfully weaned from VA-ECMO on day 7 and was discharged home on day 53. VA-ECMO can be a therapeutic option for refractory circulatory failure with significant myocardial depression in STSS.

Background: Whether temporal differences alter the clinical outcomes of patients with out-of-hospital cardiac arrest (OHCA) remains inconclusive. Furthermore, the relationship between time of day and resuscitation efforts is unknown.Methods: We studied adult OHCA patients in the Survey of Survivors after Out-of-Hospital Cardiac Arrest in the Kanto Region (SOS-KANTO) 2012 study from January 2012 to March 2013 in Japan. The primary variable was 1-month survival. The secondary outcome variables were prehospital and in-hospital resuscitation efforts by bystanders, emergency medical services personnel, and in-hospital healthcare providers. Daytime was defined as 0701 to 1500 h, evening was defined as 1501 to 2300 h, and night was defined as 2301 to 0700 h.Results: During the study period, 13,780 patients were included in the analysis. The patients with night OHCA had significantly lower 1-month survival compared to the patients with daytime OHCA (night vs. daytime, adjusted odds ratio (OR) 1.66; 95 % confidence interval (CI), 1.34-2.07; P < 0.0001). The nighttime OHCA patients had significantly shorter call-response intervals, bystander CPR, in-hospital intubation, and in-hospital blood gas analyses compared to the daytime and evening OHCA patients (call-response interval: OR 0.95 and 95 % CI 0.93-0.96; bystander CPR: OR 0.85 and 95 % CI 0.78-0.93; in-hospital intubation: OR 0.85 and 95 % CI 0.74-0.97; and in-hospital blood gas analysis: OR 0.86 and 95 % CI 0.75-0.98).Conclusions: There was a significant temporal difference in 1-month survival after OHCA. The nighttime OHCA patients had significantly decreased resuscitation efforts by bystanders and in-hospital healthcare providers compared to those with evening and daytime OHCA.

Intraabdominal bleeding from a ruptured artery aneurysm in a young adult is rare. This report describes a patient who presented to the emergency department with hemorrhagic shock caused by a ruptured aneurysm in an omental branch of the right gastroepiploic artery. The gastroepiploic artery aneurysm was successfully treated with a superselective transcatheter arterial embolization. In addition, the angiography of the superior mesenteric artery revealed multifocal stenosis, which has a typical "string-of-beads" appearance, characteristic of fibromuscular dysplasia (FMD) in the jejunal artery. Fibromuscular dysplasia is a rare disease that can cause stenosis, occlusion, aneurysm, or dissection in a medium-sized artery and is more common in women than men. The natural history, causative genes, and pathogenesis of FMD have not been fully elucidated; however, delayed diagnosis of FMD has been reported. In a young female patient with intraabdominal bleeding, clinicians should consider the possibility of a ruptured aneurysm due to FMD. Examination with early-phase angiography and endovascular treatment may reduce the need for laparotomy for hemostasis. Awareness of FMD among emergency physicians could potentially shorten diagnostic delays and increase the chances of effective examination and treatment of this condition.

Objective: Physiological parameters are crucial for the caring of trauma patients. There is a significant loss of prehospital vital signs data of patients during handover between prehospital and in-hospital teams. Effective strategies for reducing the loss remain a challenging research area. We tested whether the newly developed electronic automated prehospital vital signs chart sharing system would increase the amount of prehospital vital signs data shared with a remote trauma center prior to hospital arrival. Methods: Fifty trauma patients, transferred to a level I trauma center in Japan, were studied. The primary outcome variable was the number of prehospital vital signs shared with the trauma center prior to hospital arrival. Results: The prehospital vital signs chart sharing system significantly increased the number of prehospital vital signs, including blood pressure, heart rate, and oxygen saturation, shared with the in-hospital team at a remote trauma center prior to patient arrival at the hospital (P &lt;.0001). There were significant differences in prehospital vital signs during ambulance transfer between patients who had severe bleeding and non-severe bleeding within 24 hours after injury onset. Conclusions: Vital signs data collected during ambulance transfer via patient monitors could be automatically converted to easily visible patient charts and effectively shared with the remote trauma center prior to hospital arrival. The prehospital vital signs chart sharing system increased the number of precise vital signs shared prior to patient arrival at the hospital, which can potentially contribute to better trauma care without increasing labor and reduce information loss during clinical handover. (C) 2015 Elsevier Inc. All rights reserved.

Background: Systemic immune response to injury plays a key role in the pathophysiological mechanism of blunt trauma. We tested the hypothesis that increased blood interleukin-6 (IL-6) levels of blunt trauma patients on emergency department (ED) arrival are associated with poor clinical outcomes, and investigated the utility of rapid measurement of the blood IL-6 level. Methods: We enrolled 208 consecutive trauma patients who were transferred from the scene of an accident to a level I trauma centre in Japan and admitted to the intensive care unit (ICU). Blood IL-6 levels on ED arrival were measured by using a rapid measurement assay. The primary outcome variable was prolonged ICU stay (length of ICU stay &gt; 7 days). The secondary outcomes were 28-day mortality, probability of survival and Abbreviated Injury Scale (AIS) scores. Results: Patients with prolonged ICU stay had significantly higher blood IL-6 levels on ED arrival than the patients without prolonged ICU stay (P &lt; 0.0001). The receiver-operating characteristic curves produced an area under the curve of 0.75 (95 % confidence interval [CI], 0.66-0.84; P &lt; 0.0001) for prolonged ICU stay. The patients who had increased blood IL-6 levels on ED arrival had increased 28-day mortality (P = 0.021) and decreased probability of survival (P &lt; 0.0001). The AIS scores for the thorax, abdomen, extremity, and external body regions independently correlated with blood IL-6 levels (unstandardized coefficients [95 % CI] for the thorax: 23.8 [12.6-35.1]; P &lt; 0.0001; abdomen: 42.7 [23.8-61.7]; P &lt; 0.0001; extremity: 19.0 [5.5-32.4]; P = 0.0060; external body regions: 62.9 [13.2-112.7]; P = 0.030); the standardized coefficients for the thorax (0.27) and abdomen (0.28) were larger than those for the extremity (0.18) and external body regions (0.15). Conclusions: Increased blood IL-6 level on ED arrival was significantly associated with prolonged length of ICU stay. Blood IL-6 level on ED arrival independently correlated with the AIS scores for the abdomen and thorax, and, to a lesser extent, those for the extremity and external body regions. The rapid measurement of blood IL-6 level on ED arrival can be utilized as a fast screening tool to improve assessment of injury severity and prediction of clinical outcomes in the initial phase of trauma care.

Hereditary angioedema (HAE) is a rare genetic disease caused by a deficiency of functional C1 esterase inhibitor that causes swelling attacks in various body tissues. We hereby report a case of out-of-hospital cardiac arrest due to airway obstruction in HAE. Cutaneous swelling and abdominal pain attacks caused by gastrointestinal wall swelling are common symptoms in HAE, whereas laryngeal swelling is rare. Emergency physicians may have few chances to experience cases of life-threatening laryngeal edema resulting in a delay from symptom onset to the diagnosis of HAE. Hereditary angioedema is diagnosed by performing complement blood tests. Because safe and effective treatment options are available for the life-threatening swellings in HAE, the diagnosis potentially reduces the risk of asphyxiation in patients and their blood relatives.

Introduction: Previous studies evaluating whether subsequent conversion to shockable rhythms in patients who had initially non-shockable rhythms was associated with altered clinical outcome reported inconsistent results. Therefore, we hypothesized that subsequent shock delivery by emergency medical service (EMS) providers altered clinical outcomes in patients with initially non-shockable rhythms.Methods: We tested for an association between subsequent shock delivery in EMS resuscitation and clinical outcomes in patients with initially non-shockable rhythms (n = 11,481) through a survey of patients after out-of-hospital cardiac arrest in the Kanto region (SOS-KANTO) 2012 study cohort, Japan. The primary investigated outcome was 1-month survival with favorable neurological functions. The secondary outcome variable was the presence of subsequent shock delivery. We further evaluated the association of interval from initiation of cardiopulmonary resuscitation to shock with clinical outcomes.Results: In the univariate analysis of initially non-shockable rhythms, patients who received subsequent shock delivery had significantly increased frequency of return of spontaneous circulation, 24-hour survival, 1-month survival, and favorable neurological outcomes compared to the subsequent not shocked group (P < 0.0001). In the multivariate logistic regression analysis, subsequent shock was significantly associated with favorable neurological outcomes (vs. not shocked; adjusted P = 0.0020, odds ratio, 2.78; 95 % confidence interval, 1.45-5.30). Younger age, witnessed arrest, initial pulseless electrical activity rhythms, and cardiac etiology were significantly associated with the presence of subsequent shock in patients with initially non-shockable rhythms.Conclusions: In this study of cardiac arrest patients with initially non-shockable rhythms, patients who received early defibrillation by EMS providers had increased 1-month favorable neurological outcomes.

Liver abscess remains a life-threatening disease, particularly when it results in systemic organ failure necessitating intensive care. Only few cases of respiratory failure caused by liver abscess and treated with veno-venous extracorporeal membrane oxygenation (ECMO) have been reported. Here we present a case of liver abscess with rapid progression of multiple organ dysfunction, including severe acute respiratory failure on admission to the intensive care unit (ICU). Upon admission, we immediately initiated artificial organ support systems, including ventilator, continuous renal replacement therapy, and cardiovascular drug infusion for septic multiple organ failure and source control. Despite this initial management, respiratory failure deteriorated and V-V ECMO was introduced. The case developed abdominal compartment syndrome, for which we performed a bedside decompressive laparotomy in the ICU. The case gradually recovered from multiple organ failure and was discharged from the ICU on day 22 and from the hospital on day 53. Since liver abscess is potentially lethal and respiratory failure on admission is an additional risk factor of mortality, V-V ECMO may serve as an adjunctive choice of artificial organ support for cases of severe acute respiratory failure caused by liver abscess.

ObjectivesWhether sex affects the mortality of trauma patients remains unknown. The hypothesis of this study was that sex was associated with altered mortality rates in trauma. MethodsA retrospective review of trauma patients' records in the Japan Trauma Data Bank was conducted (n=80,813) from 185 major emergency hospitals across Japan. The primary outcome variable was in-hospital mortality within 28days. Secondary outcome variables included serious injuries to different body regions with an Abbreviated Injury Scale of 3. ResultsIn the analysis of 80,813 trauma patients, males had significantly greater 28-day mortality compared to females (adjusted p=0.0072, odds ratio [OR]=1.14, 95% confidence interval [CI]=1.06 to 1.23) via logistic regression analysis adjusted for age, mechanism, Injury Severity Score, Revised Trauma Score, and potential preexisting risk factors. Of 10 injury categories examined, sex significantly affected in-hospital 28-day mortality rate in falls (adjusted p&lt;0.0001, OR= 1.34, 95% CI=1.19 to 1.52). Further analysis of three fall subcategories by falling distance revealed that male patients who fell from ground level had significantly higher 28-day mortality (adjusted p&lt;0.0001, OR= 1.75, 95% CI=1.43 to 2.14) and a significantly greater frequency of serious injury to the head, thorax, abdomen, and spine, but a lower frequency of serious injury to the extremities, compared to female patients. ConclusionsCompared to female trauma patients, male trauma patients had greater 28-day mortality. In particular, ground-level falls had a significant sex difference in mortality, with serious injury to different body regions. Sex differences appeared to be important for fatalities from ground-level falls.

Objectives: Mortality from septic shock is highly heritable. The identification of causal genetic factors is insufficient. To discover key contributors, we first identified nonsynonymous single-nucleotide polymorphisms in conserved genomic regions that are predicted to have significant effects on protein function. We then test the hypothesis that these nonsynonymous single-nucleotide polymorphisms across the genome alter clinical outcome of septic shock. Design: Genetic-association study plus in vitro experiment using primary cells plus in silico analysis using genomic DNA and protein database. Setting: Twenty-seven ICUs at academic teaching centers in Canada, Australia, and the United States. Patients: Patients with septic shock of European ancestry (n = 520). Interventions: Patients with septic shock were genotyped for 843 nonsynonymous single-nucleotide polymorphisms in conserved regions of the genome and are predicted to have damaging effects from the protein sequence. Measurements and Main Results: The primary outcome variable was 28-day mortality. Secondary outcome variables were organ dysfunction. Productions of adhesion molecules including interleukin-8, growth-regulated oncogene-alpha, monocyte chemoattractant protein-1, and monocyte chemoattractant protein-3 were measured in human umbilical vein endothelial cells after SVEP1 gene silencing by RNA interference. Patients with septic shock having the SVEP1 C allele of nonsynonymous single-nucleotide polymorphism, SVEP1 c.2080A&gt;C (p. Gln581His, rs10817033), had a significant increase in the hazard of death over the 28 days (hazard ratio, 1.72; 95% CI, 1.31-2.26; p = 9.7 x 10-5) and increased organ dysfunction and needed more organ support (p &lt; 0.05). Silencing SVEP1 significantly increased interleukin-8, growth-regulated oncogene-alpha, monocyte chemoattractant protein-1, monocyte chemoattractant protein-3 production in human umbilical vein endothelial cells under lipopolysaccharide stimulation (p &lt; 0.01). Conclusions: C allele of SVEP1 c.2080A&gt;C (p. Gln581His) single-nucleotide polymorphism, a non-synonymous single-nucleotide polymorphism in conserved regions and predicted to have damaging effects on protein structure, was associated with increased 28-day mortality and organ dysfunction of septic shock. SVEP1 appears to regulate molecules of the leukocyte adhesion pathway.

Background: Genetic variations contribute to septic shock mortality. To discover a novel locus, we performed in vitro genome-wide association studies (GWAS) and further tested the result in a cohort of septic shock patients. Methods: Two in vitro GWAS using a quantitative trait locus analysis of stimulated IL-6 production in lymphoblastoid cells from 60 individuals of European ancestry were performed. VPS13D rs6685273 was genotyped in European ancestry patients (n = 498). The VPS13D gene was silenced in vitro. Results: Two GWAS using lymphoblastoid cells identified the locus of VPS13D rs6685273 that was significant in the same direction in both GWAS. The VPS13D rs6685273 C allele was associated with increased IL-6 production. Patients with septic shock who had the VPS13D rs6685273 CC genotype had an increased 28-day mortality (p = 0.023) and more organ failure (p &lt; 0.05) compared to the CT/TT genotypes. VPS13D in vitro gene silencing in the HeLa cell line increased IL-6 production. Furthermore, the rs6685273 genotype was associated with differential VPS13D splice variant expression. Conclusions: The VPS13D rs6685273 C allele was associated with increased IL-6 production in vitro. The patients with the VPS13D rs6685273 CC genotype had increased 28-day mortality and increased organ failure. VPS13D appears to regulate IL-6 production. (C) 2015 S. Karger AG, Basel