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Summary Background CT radiation is arguably carcinogenic. Results from single-centre studies, mostly retrospective, have advocated lowering the CT radiation dose for the diagnosis of appendicitis. However, adoption of low-dose CT has been slow. We aimed to assess the effectiveness of low-dose CT compared with standard-dose CT in the diagnosis of appendicitis in adolescents and young adults. Methods We did this pragmatic, multicentre, randomi s ed controlled non-inferiority trial at 20 South Korean teaching hospitals with little experience with low-dose CT. Patients aged 15–44 years with suspected appendicitis were randomly assigned (1:1), via computer-generated random assignments (permuted block sizes of two, four, six, and eight) concealed in sequentially numbered envelopes, to receive low-dose CT (2 mSv) or standard-dose CT (≤8 mSv). Randomisation was stratified by site. Group allocation was concealed from patients, outcome assessors, and adverse event adjudicators; care providers, site pathologists, and data collectors were aware of allocation. The primary endpoint was the negative (unnecessary) appendectomy rate among all appendectomies, with a non-interiority margin of 4·5% for low-dose versus standard-dose CT. Primary analy s is was by modified intention to treat, which included all patients who received an appendectomy in the group to which they were assigned. This trial is registered with ClinicalTrials.gov, number NCT01925014. Findings Between Dec 4, 2013, and Aug 18, 2016, we assigned 1535 patients to the low-dose CT group and 1539 patients to the standard-dose CT group. 22 (3·9%) of 559 patients had a negative appendectomy in the low-dose group versus 16 (2·7%) of 601 patients in the standard-dose group (difference 1·3%, 95% CI −0·8 to 3·3; p=0·0022 for the non-inferiority test). We recorded 43 adverse events in 43 (2·8%) of 1535 patients in the low-dose group and 41 adverse events in 40 (2·6%) of 1539 patients in the standard-dose group. One life-threatening adverse event of anaphylaxis caused by an iodinated contrast material occurred in the low-dose group. Interpretation Radiation dose of appendiceal CT for adolescents and young adults can be reduced to 2 mSv without impairing clinical outcomes. In view of the vast number of appendiceal CT examinations done worldwide, use of low-dose CT could prevent a sizeable number of radiation-associated cancers in the future. Funding Korea Health Industry Development Institute, Seoul National University Bundang Hospital, Dasol Life Science, and Bracco Imaging Korea.

Background The inhibition of mitochondrial permeability transition pore opening during ischemia-reperfusion can ameliorate injuries. This study aimed to investigate the effects of cyclosporine A (CsA) in rats after hemorrhagic shock. Methods Male Sprague-Dawley rats were subjected to pressure-controlled hemorrhagic shock (mean arterial pressure, 38 ± 1 mm Hg) for 90 minutes. After the hemorrhagic shock period, rats were randomly allocated to one of three groups as follows: a control group, a CsA10 group, or a CsA50 group. CsA for the treatment groups (10 mg/kg for the CsA10 group and 50 mg/kg for the CsA50 group) or normal saline for the control group was administered via tail vein for 10 minutes, and shed blood was transfused for 15 minutes. For the survival study, animals were observed for up to 9 hours, and their survival time was recorded until death. Separate experiments were performed to examine the effect of CsA on inflammatory responses and liver injury. Rats were sacrificed at 210 minutes after the shock period, and blood and liver tissues were harvested. Results Survival times were shown to be significantly longer in the CsA-treated groups (i.e., the CsA10 and CsA50 groups) than in the control group. Plasma interleukin-6 and thiobarbituric acid-reactive substances were significantly lower in the CsA50 group than in the control group and phosphorylation of Akt, GSK-3β, and Bad were significantly increased in the CsA-treated groups compared with the control group. Expressions of Bcl-2, cleaved caspase 3, and cytoplasmic cytochrome C were significantly decreased in the CsA-treated groups compared with the control group. Although histologic liver injury was not significantly different among the groups, ultrastructural changes of mitochondria were more prominent in the control group than in the CsA-treated groups. Conclusion CsA increased survival time, decreased proinflammatory cytokine and lipid peroxidation, and augmented Akt survival pathways in rats subjected to pressure-controlled hemorrhagic shock.

A 42-year-old man visited the emergency department complaining of lower extremity swelling and myalgia. His influenza A antigen test was positive, and he was admitted for supportive care of severe myalgia. On the first hospital day, the swelling in his lower legs was aggravated with intolerable pain, and his creatine phosphokinase and hemoglobin levels were elevated. He was treated with massive hydration, albumin replacement, continuous venovenous hemofiltration, phlebotomy, and oseltamivir. The swelling and pain in his extremities were decreased without renal dysfunction, even though peripheral neuropathy and muscular complication persisted. Systemic capillary leak syndrome is a rare but life-threatening condition. The diagnosis is made clinically based on a classic triad of hypotension, hypoalbuminemia, and hemoconcentration. In our case, the influenza A infection was related to the capillary leakage.

This study was performed to investigate the association of red cell distribution width (RDW) with 28-day mortality in patients with severe sepsis and septic shock.We performed a retrospective analysis of patients with severe sepsis and septic shock. Patients' demographic data, comorbidities, the blood test results including RDW at admission to the emergency department, and Acute Physiologic and Chronic Health Evaluation II score were compared between 28-day survivors and nonsurvivors. Red cell distribution width was categorized into tertiles as 14% or less, 14.1% to 15.7%, and 15.8% or greater. Multivariate Cox proportional hazards regression analysis was performed to determine the risk factors for mortality.A total of 566 patients were included, and overall mortality was 29%. Red cell distribution width was significantly higher in nonsurvivors than in survivors, and the corresponding mortality of patients with an RDW of 14% or less, 14.1% to 15.7%, and 15.8% or greater was 13.1%, 30.1%, and 44.9%, respectively (P.001). In Cox proportional hazards analysis, groups with higher RDW are independently associated with 28-day mortality compared with groups with an RDW of 14.0% or less: RDW 14.1% to 15.7% (hazard ratio, 1.66; 95% confidence interval [CI], 1.00-2.76) and RDW of 15.8% or greater (hazard ratio, 2.57; 95% CI, 1.53-4.34). The area under the receiver operating curve of RDW was 0.68 (95% CI, 0.63-0.72).Red cell distribution width is associated with 28-day mortality in patients with severe sepsis and septic shock.

s Objective This study was performed to evaluate whether heart-type fatty acid–binding protein (H-FABP) could predict 28-day mortality in patients with severe sepsis and septic shock. Methods We performed a prospective observational study and included consecutive patients with severe sepsis and septic shock. Patients' demographic data, Acute Physiology and Chronic Health Evaluation (APACHE) II score, and the blood test results including H-FABP concentrations were compared between the 28-day survivors and nonsurvivors. The association between the concentration of H-FABP and survival was analyzed with multivariate logistic regression and Cox proportional hazards regression analyses. The prognostic performance of H-FABP was compared with those of the APACHE II score and albumin using the area under the receiver operating characteristic curve. Results Of the 99 patients, 38 (38%) died. The mortality rate increased with increasing H-FABP concentration. In multivariate logistic regression analyses, H-FABP greater than 40 ng/mL was an independent predictor of mortality compared with H-FABP less than 7 ng/mL (odds ratios, 9.23; 95% confidence interval, 1.29-65.86). By Cox proportional hazards analysis, H-FABP greater than 40 ng/mL was associated with a 5.57-fold increased risk for death during the 28-day follow-up period (hazard ratio, 5.57; 95% confidence interval, 1.20-25.80). The area under the receiver operating characteristic curve of H-FABP was 0.739 (95% confidence interval, 0.640-0.839), which was comparable with those of the APACHE II score and albumin. Conclusion The H-FABP was an independent prognostic factor and could be a useful biomarker for 28-day mortality in patients with severe sepsis and septic shock.

MRI-based prognostication of comatose cardiac arrest survivors has shown promising results. However, the technique has not been validated in patients treated with therapeutic hypothermia and it is unknown how it might add to NSE-based prognostication. We sought to evaluate the prognostic performance of regional apparent diffusion coefficient (ADC) in comatose out-of-hospital cardiac arrest (OHCA) patients treated with mild hypothermia and its added value to NSE-based prognostication.An OHCA registry was analyzed to identify OHCA patients older than 15 who were treated with therapeutic hypothermia and underwent brain MRI between 2008 and 2011. Quantitative measurement of regional ADCs was performed by a radiologist blinded to the clinical outcome.Of the 43 eligible patients, 11 (18.6 %) achieved a good outcome (6-month CPC of 1 or 2). The regional ADC of the occipital cortex showed the highest discriminatory power with an area under the curve of receiver operating characteristic (AUROC) of 0.943 (95 % CI, 0.872-1.000) and predicted poor outcomes with a sensitivity of 90.6 % and a specificity of 100 %. The AUROC for NSE levels (48-h) was 0.911 (95 % CI, 0.801-1.000) which was significantly correlated with the regional ADC (Pearson's r = -0.674, p.001). The ADC-based predictions identified an additional 5 (35.7 %) poor outcome patients out of 14 with 48-h NSE levels less than 78.9 ng/mL, which is the cutoff point suggested in a previous study. However, additional prognostic information was not provided when the 48-h NSE levels were78.9 ng/mL.Regional ADC-based prognostication was accurate in OHCA patients who were treated with mild hypothermia. However, it only provided additional prognostic information when the 48-h NSE levels indicated a good prognosis (48-h NSE78.9 ng/mL).

Hemorrhagic shock, and subsequent resuscitation leads to global ischemia/reperfusion injury. It may result in multiple organ injury and death. Ischemic post-conditioning has been suggested to reduce organ injury. It may lead to gradual increase in tissue oxygen delivery and tissue acidosis may be reduced gradually. Gradual increase of blood pressure or blood flow in ischemic organs has been reported to decrease tissue injury. We propose that gradual and stepwise increase of blood pressure may decrease tissue injury and mortality in hemorrhagic shock by mimicking ischemic post-conditioning.

We sought to investigate the prognostic implication of early coagulopathy represented by initial DIC score in out-of-hospital cardiac arrest (OHCA).OHCA registry was analyzed to identify patients with ROSC without recent use of anticoagulant between 2008 and 2011. Patients were assessed for prehosptial factors, initial laboratory results and therapeutic hypothermia. Outcome variables were survival discharge, 6-month CPC and survival duration within the first week after ROSC. Logistic regression and Cox proportional hazards models were used for both univariable and multivariable analysis.Among 273 eligible patients, initial DIC score was available in 252 (92.3%). Higher DIC score was associated with increased inhospital death (odds ratio [OR], 1.89 per unit; 95% confidence interval [CI], 1.48-2.41) and unfavorable long-term outcome (6-month CPC 3-5; OR, 2.21 per unit; 95% CI, 1.60-3.05). The adjusted ORs for both outcomes were 1.61 (95% CI, 1.17-2.22) and 1.84 (95% CI, 1.26-2.67), respectively. We categorized DIC score in five groups as3, 3, 4, 5 and5 and analyzed differential mortality risk using Cox proportional hazards model. Compared with reference group (DIC score3), the adjusted HR for early mortality in each remaining group was 1.96 (95% CI, 1.13-3.40), 2.26 (95% CI, 1.27-4.02), 2.77 (95% CI, 1.58-4.85) and 4.29 (95% CI, 2.22-8.30), respectively (p-trend0.001). The area under the receiver operating characteristic of DIC score for prediction of unfavorable long-term outcome was 0.79 (95% CI, 0.69-0.88).Increased initial DIC score in OHCA was an independent predictor for poor outcomes and early mortality risk.

Aim of study The effects of therapeutic hypothermia (HT) during experimental sepsis may be influenced by disease severity. We experimentally investigated the effect of therapeutic HT on varying disease severity in a septic rat model. Materials and methods An adult male Sprague-Dawley rat model of intra-abdominal sepsis was used. To modify the disease severity, we used two different models; a moderate severe sepsis model (MSSM) and a severe septic shock model (SSSM). All rats were randomized to a hypothermia group (HT, 30–32 °C) or a normothermia group (NT, 36–38 °C) 1 h after sepsis induction in each model. HT was maintained for 4 h and rewarming was conducted for 2 h. Survival time was recorded for up to 12 h in the SSSM group and 24 h in the MSSM group. Acute lung and liver injury, cytokine, and malondialdehyde (MDA) levels were investigated 7 h after sepsis induction. Hemodynamic profiles were also evaluated. Results In the SSSM, there were survival benefits and reduced acute lung and liver injury with therapeutic HT. Therapeutic HT was also associated with significantly reduced levels of plasma interleukin-6 and tissue malondialdehyde (MDA) levels in the liver and lung compared with the NT group in the SSSM. There was a tendency for the mean arterial pressure to be higher in the HT group compared to the NT group in the SSSM. In MSSM, however, there was no such beneficial effect. Conclusion In this rat model of severe septic shock, therapeutic HT showed beneficial effects. In contrast, therapeutic HT did not show protective effect in the moderate sepsis model.

Therapeutic hypothermia has been proposed to protect organs in some diseases. However, the effect of therapeutic hypothermia on liver injury in sepsis is unknown. The aim of this study was to evaluate the effects of therapeutic hypothermia on liver injury in sepsis.Male Sprague-Dawley rats underwent cecal ligation and incision (CLI). We randomly allocated rats into one of two groups 1 h after CLI: hypothermia (HT) and normothermia (NT). In the HT group, body temperature decreased to 32°C ± 0.5°C and was maintained 4 h, followed by rewarming to 37°C for 2 h. In the NT group, body temperature was maintained at 37°C ± 0.5°C throughout the experimental periods. At 7 h after CLI, we harvested blood and liver tissues and measured serum alanine aminotransferase and the histological liver injury score. We performed immunohistochemistry for cleaved caspase-3 and evaluated phosphorylation of Akt, GSK-3β and Bad with the Western blot assay.Serum alanine aminotransferase was significantly lower in the HT group than in the NT group (57.0 ± 6.0 IU/L versus 192.5 ± 92.5 IU/L; P = 0.028). The histological liver injury score was also significantly lower in the HT group than in the NT group (2.9 ± 0.5 versus 5.4 ± 0.6; P = 0.016). Phosphorylation of Akt, GSK-3β, and Bad was significantly increased in the HT group compared with the NT group (P0.001, P = 0.007, and P = 0.001, respectively). Hypothermia significantly mitigated expression of cleaved caspase-3 compared with the NT group (P = 0.032).Therapeutic hypothermia attenuated liver injury in a polymicrobial sepsis model of rats by enhancing the Akt signaling pathway and decreasing apoptosis.

Background Red cell distribution width (RDW) is associated with mortality in both the general population and in patients with certain diseases. However, the relationship between RDW and mortality in patients with community-acquired pneumonia (CAP) is unknown. The objective of this study was to evaluate the association of RDW with mortality in patients with CAP. Methods We performed a retrospective analysis of a prospective registry database of patients with CAP. Red cell distribution width was organized into quartiles. The pneumonia severity index (PSI) and CURB-65 were calculated. The primary outcome was 30-day mortality. Secondary outcomes included the length of hospital stay, admission to the intensive care unit, vasopressor use, and the need for mechanical ventilation. Results A total of 744 patients were included. The PSI and CURB-65 were higher in patients with a high RDW. Multivariate logistic regression analysis identified higher categories of RDW, PSI, CURB-65, and albumin as statistically significant variables. Thirty-day mortality was significantly higher in patients with a higher RDW. Among the secondary outcomes, the length of hospital stay and vasopressor use were significantly different between the groups. In a Cox proportional hazard regression analysis, patients with higher categories of RDW exhibited increased mortality before and after adjustment of the severity scales. Receiver operating characteristics curves demonstrated improved mortality prediction when RDW was added to the PSI or CURB-65. Conclusion Red cell distribution width was associated with 30-day mortality, length of hospital stay, and use of vasopressors in hospitalized patients with CAP. The inclusion of RDW improved the prognostic performance of the PSI and CURB-65.

Post-resuscitation period is characterized by high early mortality due to post-cardiac arrest syndrome. Recent studies found that elevated red cell distribution width (RDW) is a strong predictor of mortality in critically ill patients. We investigated the prognostic significance of RDW in out-of-hospital cardiac arrest (OHCA) victims.Analysis of emergency department OHCA registry extending from January 2007 to December 2010 was conducted. Patients with ROSC were assessed for Utstein predictors including sex, age, arrest location, presence of witness, bystander cardiopulmonary resuscitation, response time, initial rhythm and cause of arrest. RDW, hematocrit, white blood cell and platelet counts, blood urea nitrogen (BUN), creatinine and albumin were also obtained. Outcome variable was survival duration within 30 days. RDW was categorized in quartiles as13.2%, 13.2% to 14.0%, 14.1% to 15.4% and15.4%. Hazard ratios (HRs) were estimated using Cox-proportional hazard models in both univariate and multivariate analysis. All prognostic variables with their p value0.1 in univariate analysis were used in multivariate analysis for adjustment.Among 409 OHCA patients, 219 patients had ROSC. Highest RDW quartile (RDW15.4%), female sex, older age, non-shockable initial rhythm, increased BUN and creatinine and decreased albumin, hematocrit and platelet count were associated with increased mortality in univariate analysis. In multivariate analysis, the highest RDW quartile was independently associated with all-cause mortality (HR=1.95; 95% CI 1.05-3.60; p=0.034) during 30-day post-resuscitation period. Other significant variables were age, initial rhythm and serum albumin.Initial RDW is an independent predictor of all-cause mortality in post-resuscitation patients.