Sung-Hyuk Choi

Burn-induced gut barrier injury is attenuated by phosphodiesterase inhibition: Effects on tight junction structural proteins

Loss of intestinal barrier function after burn injury allows movement of intraluminal contents across the mucosa, which can lead to the development of distant organ injury and multiple organ failure. Tight junction function is highly regulated by membrane-associated proteins including occludin and zonula occludens protein 1 (ZO-1), which can be modulated by systemic inflammation. We hypothesized that (1) burn injury leads to gut barrier injury, and (2) phosphodiesterase inhibition will attenuate these burn-induced changes. Male balb/c mice undergoing a 30% steam burn were randomized to resuscitation with normal saline or normal saline + pentoxifylline (PTX; 12.5 mg/kg). Intestinal injury was assessed by histological diagnosis and TNF-&agr; levels using enzyme-linked immunosorbent assay. Intestinal permeability was assessed by measuring the plasma concentration of fluorescein isothiocyanate-dextran after intraluminal injection in the distal ileum. Occludin and ZO-1 levels were analyzed by immunoblotting and immunohistochemistry. Thirty percent total body surface area (TBSA) burn results in a significant increase in intestinal permeability. Treatment with PTX after burn attenuates intestinal permeability to sham levels. Burn injury resulted in a marked decrease in the levels of tight junction proteins occludin and ZO-1 at 6 and 24 h. The use of PTX after burn significantly decreases the breakdown of occludin and ZO-1. Pentoxifylline also attenuates the burn-induced increase in plasma and intestinal TNF-&agr;. Confocal microscopy demonstrates that PTX attenuates the burn-induced reorganization of occludin and ZO-1 away from the tight junction. Pentoxifylline attenuates burn-induced intestinal permeability and decreases the breakdown and reorganization of intestinal occludin and ZO-1. Therefore, phosphodiesterase inhibition may be a useful adjunct strategy in the attenuation of burn-induced gut barrier injury.

Phosphodiesterase inhibition attenuates alterations to the tight junction proteins occludin and ZO-1 in immunostimulated Caco-2 intestinal monolayers.

AIMSnUnder normal conditions, the intestinal mucosa acts as a local barrier to prevent the influx of luminal contents. The intestinal epithelial tight junction is comprised of several membrane associated proteins, including zonula occludens-1 (ZO-1) and occludin. Disruption of this barrier can lead to the production of pro-inflammatory mediators and ultimately multiple organ failure. We have previously shown that Pentoxifylline (PTX) decreases histologic gut injury and pro-inflammatory mediator synthesis. We hypothesize that PTX prevents the breakdown of ZO-1 and occludin in an in vitro model of immunostimulated intestinal cell monolayers.nnnMAIN METHODSnCaco-2 human enterocytes were grown as confluent monolayers and incubated under control conditions, or with PTX (2 mM), Cytomix (TNF-alpha, IFN-gamma, IL-1), or Cytomix+PTX for 24 h. Occludin and ZO-1 protein levels were analyzed by Western blot. Confocal microscopy was used to assess the cytoplasmic localization of ZO-1 and occludin.nnnKEY FINDINGSnCytomix stimulation of Caco-2 cells resulted in a 50% decrease in both occludin and ZO-1 protein. Treatment with Cytomix+PTX restored both occludin and ZO-1 protein to control levels. Confocal microscopy images show that Cytomix caused an irregular, undulating appearance of ZO-1 and occludin at the cell junctions. Treatment with PTX prevented the Cytomix-induced changes in ZO-1 and occludin localization.nnnSIGNIFICANCEnTreatment with PTX decreases the pro-inflammatory cytokine induced changes in the intestinal tight junction proteins occludin and ZO-1. Pentoxifylline may be a useful adjunct in the treatment of sepsis and shock by attenuating intestinal barrier breakdown.

Korean Shock Society septic shock registry: a preliminary report

Objective To evaluate the clinical characteristics, therapeutic interventions, and outcomes of patients with septic shock admitted to the emergency department (ED). Methods This study was a preliminary, descriptive analysis of a prospective, multi-center, observational registry of the EDs of 10 hospitals participating in the Korean Shock Society. Patients aged 19 years or older who had a suspected or confirmed infection and evidence of refractory hypotension or hypoperfusion were included. Results A total of 468 patients were enrolled (median age, 71.3 years; male, 55.1%; refractory hypotension, 82.9%; hyperlactatemia without hypotension, 17.1%). Respiratory infection was the most common source of infection (31.0%). The median Sepsis-related Organ Failure Assessment score was 7.5. The sepsis bundle compliance was 91.2% for lactate measurement, 70.3% for blood culture, 68.4% for antibiotic administration, 80.3% for fluid resuscitation, 97.8% for vasopressor application, 68.0% for central venous pressure measurement, 22.0% for central venous oxygen saturation measurement, and 59.2% for repeated lactate measurement. Among patients who underwent interventions for source control (n=117, 25.1%), 43 (36.8%) received interventions within 12 hours of ED arrival. The in-hospital, 28-day, and 90-day mortality rates were 22.9%, 21.8%, and 27.1%, respectively. The median ED and hospital lengths of stay were 6.8 hours and 12 days, respectively. Conclusion This preliminary report revealed a mortality of over 20% in patients with septic shock, which suggests that there are areas for improvement in terms of the quality of initial resuscitation and outcomes of septic shock patients in the ED.

Clinical outcome comparison of patients with septic shock defined by the new sepsis-3 criteria and by previous criteria

BackgroundnWe compared the clinical characteristics and outcomes between the new definition of sepsis-3 septic shock and the definition previously used from 1991 until recently.nnnMethodsnWe conducted an observational study using a prospective, multi-center registry of septic shock from October 2015 to February 2017. Registry data were collected by 10 emergency departments (EDs) in tertiary hospitals that are members of the Korean Shock Society. Data on septic shock patients who met the previous septic shock definition were collected. The patients were divided into a sepsis-3 defined septic shock group, made up of those who met the new criteria for refractory hypotension with hyperlactatemia, and a group of those who met only the 1991 definition for septic shock. The primary outcome was 90-day mortality, and secondary outcomes were 28-day mortality and in-hospital mortality.nnnResultsnOf all 1,028 included patients, 574 (55.8%) met the septic shock criteria for sepsis-3, leaving 454 patients who met only the previous definition. Those who met the sepsis-3 criteria demonstrated higher comorbidity than those who met the previous definition (83.1% vs. 75.3%, P<0.01), but there was no difference in infection focus. The sequential organ failure assessment (SOFA) (initial/maximal), the acute physiology, and the chronic health evaluation II scores were significantly higher in for those who met the sepsis-3 criteria [6.5±3.1 vs. 5.0±2.9, 9.3±3.8 vs. 6.6±3.4, and 20.0 (15.0-26.0) vs. 15.0 (10.0-20.3), respectively; P<0.01]. The 90-day mortality was significantly higher in the sepsis-3 group (32.1% vs. 23.3%; P<0.01). In-hospital and 28-day mortality were also higher in the sepsis-3 group (26.8% vs. 17.1% and 25.1% vs. 16.5%, respectively; P<0.01).nnnConclusionsnThe new definition of septic shock successfully selected patients with greater severities and worse outcomes.

Prognosis of patients excluded by the definition of septic shock based on their lactate levels after initial fluid resuscitation: a prospective multi-center observational study

BackgroundSeptic shock can be defined both by the presence of hyperlactatemia and need of vasopressors. Lactate levels should be measured after volume resuscitation (as per the Sepsis-3 definition). However, currently, no studies have evaluated patients who have been excluded by the new criteria for septic shock. The aim of this study was to determine the clinical characteristics and prognosis of these patients, based on their lactate levels after initial fluid resuscitation.MethodsThis observational study was performed using a prospective, multi-center registry of septic shock, with the participation of 10 hospitals in the Korean Shock Society, between October 2015 and February 2017. We compared the 28-day mortality between patients who were excluded from the new definition (defined as lactate level <2 mmol/L after volume resuscitation) and those who were not (≥2 mmol/L after volume resuscitation), from among a cohort of patients with refractory hypotension, and requiring the use of vasopressors. Other outcome variables such as in-hospital mortality, intensive care unit (ICU) stay (days), Sequential Organ Failure Assessment (SOFA) scores and Acute Physiology and Chronic Health Evaluation (APACHE) II scores were also analyzed.ResultsOf 567 patients with refractory hypotension, requiring the use of vasopressors, 435 had elevated lactate levels, while 83 did not have elevated lactate levels (either initially or after volume resuscitation), and 49 (8.2%) had elevated lactate levels initially, which normalized after fluid resuscitation. Thus, these 49 patients were excluded by the new definition of septic shock. These patients, in whom perfusion was restored, demonstrated significantly lower age, platelet count, and initial and subsequent lactate levels (all pu2009<u20090.01). Similarly, significantly lower 28-day mortality was observed in these patients than in those who had not been excluded (8.2% vs 25.5%, pu2009=u20090.02). In-hospital mortality and the maximum SOFA score were also significantly lower in the excluded patients group (pu2009=u20090.03, both).ConclusionsIt seems reasonable for septic shock to be defined by the lactate levels after volume resuscitation. However, owing to the small number of patients in whom lactate levels were improved, further study is warranted.

Risk factors for sepsis in Korean trauma patients

PurposeSepsis in severely injured patients is one of the leading causes of death in hospitals. The incidence of and risk factors for sepsis after trauma have been studied outside, but not within Korea. Therefore, this study investigated the incidence of sepsis and the independent risk factors for sepsis in moderately to severely injured patients in Korea.MethodsThe electronic medical records of patients who visited the emergency department from January 2010 to December 2012 were reviewed retrospectively. Patients older than 18xa0years of age with an Injury Severity Score (ISS) greater than or equal to nine points were included.ResultsA total of 183 patients met the study inclusion criteria. The median ISS was 14 (range 9–17) points and 15 (8xa0%) patients developed sepsis. The patients’ age [adjusted OR, 1.053; 95xa0% confidence intervals (CI), 1.015–1.094], ISS (adjusted OR, 1.114; 95xa0% CI, 1.046–1.187), and emergency surgery (adjusted OR, 3.727; 95xa0% CI, 1.051–13.221) were independent risk factors for post-traumatic sepsis.ConclusionsAmong the risk factors identified in the literature, our research confirmed only the patients’ age and ISS as risk factors for sepsis after trauma, and, additionally, identified emergency surgery as a risk factor in Korean patients. Therefore, trauma patients who have any of the risk factors mentioned above have a high risk of post-traumatic sepsis, which requires certain precautionary clinical measures.

Understanding the characteristics of recurrent visits to the emergency department by paediatric patients: a retrospective observational study conducted at three tertiary hospitals in Korea

Objectives The number of paediatric patients visiting the emergency department (ED) continues to rise. In South Korea, approximately 25% of the patients who visit the ED are paediatric patients. In the USA, about 20% of the paediatric population were found to have visited the ED in the past year. A recent study demonstrated that 4.5%–8% of patients account for 25% of all ED visits. Therefore, the aim of this study was to identify the characteristics of recurrent visits. Methods Design: retrospective observational study. Setting: this study examined and analysed medical record data involving three tertiary EDs. Participants: a total of 46 237 ED visits by patients <16 years during 1-year period. Main outcome measures: data collected included the number of recurrent ED patients, frequency of recurrent visits, age, sex, insurance status, period until recurrent visit (days), main diagnosis and ED discharge results. Results Excluding patients with multiple visits, the total number of paediatric patients who fit the study criteria was 33u2009765. Among these patients, 23u2009384 (69.2%) had no recurrent ED visits in the subsequent year after their first visit. A total of 15u2009849 (46.8%) patients were toddlers (between age 1 and 4 years). In the patient group without a recurrent visit, fever was the most common diagnosis. Conclusions Our study reviewed medical records to inspect the characteristics of patients who return to care. Higher recurrent visit frequency was associated with using the 119 rescue centre service, having a medical condition, with younger age and a higher rate of hospitalisation. Analysis of the factors associated with frequent ED visits will help to improve care for paediatric patients who visit the ED.

Learning curve and period of experience required for the competent diagnosis of acute appendicitis using abdominal computed tomography: a prospective observational study

Objective To assess the learning curve of novice residents in diagnosing acute appendicitis using abdominal computed tomography (CT) scans. Methods This prospective observational study was conducted within a 4-month period from March 1 to June 30, 2015. After CT scans for right lower quadrant pain or similar acute abdomen were evaluated, postgraduate year 1 (PGY-1) residents completed an interpretation checklist. The primary outcome was evaluation of the learning curve for competent CT scan interpretation under suspicion of acute appendicitis. Secondary outcomes were cumulative numbers of accurate abdominal CT interpretations regardless of initial clinical impression and training period. Results PGY-1 residents recorded a total of 230 interpretation checklists. There were 53, 51, 46, 44, and 36 checklists recorded by individual residents and 92, 92, 91, 91, and 61 respective training days in the emergency department, excluding rotation periods in other departments. After 16 to 20 interpretations of abdominal CT scans performed under suspicion of acute appendicitis, the residents could diagnose acute appendicitis with more than 95% accuracy. Overall, the sensitivity and specificity for diagnosing acute appendicitis were 97% (95% confidence interval, 94 to 100) and 83% (95% confidence interval, 80 to 87), respectively. After 61 to 80 abdominal CT interpretations regardless of suspicion of acute appendicitis and after 41 to 50 days in training, PGY-1 emergency department residents could diagnose acute appendicitis with more than 95% accuracy. Conclusion PGY-1 residents require 16 to 20 checklist interpretations to acquire acceptable abdominal CT interpretation. After performing 61 to 80 CT scans regardless of suspicion of acute appendicitis, they could diagnose acute appendicitis with acceptable accuracy.