Weidun Alan Guo

The receptor for advanced glycation end products and acute lung injury/acute respiratory distress syndrome

The receptor for advanced glycation end products (RAGE) is a pattern-recognition receptor and evolutionary member of the immunoglobulin superfamily that is involved in the host response to infection, injury, and inflammation. It exists in two forms: membrane-bound and soluble forms (sRAGE). RAGE recognizes a variety of ligands and, via a receptor-driven signaling cascade, activates the transcription factor NF-κB, leading to the expression of proinflammatory cytokines. The soluble form, sRAGE, is a decoy receptor and competitively inhibits membrane RAGE activation. RAGE is constitutively expressed abundantly in the lung under basal conditions. This expression is enhanced during inflammatory states such as with acute lung injury (ALI) and acute respiratory distress syndrome (ARDS). This review summarizes the characteristics of RAGE, RAGE isoforms, RAGE ligands, and signaling pathways in the pathogenesis of ALI and ARDS. Additionally, the review explores the potential of RAGE as an important therapeutic target in ALI/ARDS.

Do we really rely on fast for decision-making in the management of blunt abdominal trauma?

INTRODUCTION The Focused Assessment with Sonography in Trauma examination (FAST) is currently taught and recommended in the ATLS(®), often as an addendum to the primary survey for patients with blunt abdominal trauma. Although it is non-invasive and rapidly performed at bedside, the utility of FAST in blunt abdominal trauma has been questioned. We designed this study to examine our hypothesis that FAST is not an efficacious screening tool for identifying intra-abdominal injuries. METHODS We performed a retrospective chart review of all patients with confirmatory diagnosis of blunt abdominal injuries with CT and/or laparotomy for a period of 1.5 years (from 7/2009 to 11/2010). FAST was performed by ED residents and considered positive when free intra-abdominal fluid was visualized. Abdominal CT, or exploratory laparotomy findings were used as confirmation of intra-abdominal injury. RESULTS A total of 1671 blunt trauma patients were admitted to and evaluated in the Emergency Department during a 1½ year period and 146 patients were confirmed intra-abdominal injuries by CT and/or laparotomy. Intraoperative findings include injuries to the liver, spleen, kidneys, and bowels. In 114 hemodynamically stable patients, FAST was positive in 25 patients, with a sensitivity of 22%. In 32 hemodynamically unstable patients, FAST was positive in 9 patients, with a sensitivity of 28%. A free peritoneal fluid and splenic injury are associated with a positive FAST on univariate analysis, and are the independent predictors for a positive FAST on multiple logistic regression. CONCLUSION FAST has a very low sensitivity in detecting blunt intraabdominal injury. In hemodynamically stable patients, a negative FAST without a CT may result in missed intra-abdominal injuries. In hemodynamically unstable blunt trauma patients, with clear physical findings on examination, the decision for exploratory laparotomy should not be distracted by a negative FAST.

Advanced Glycation End Products Induce Obesity and Hepatosteatosis in CD-1 Wild-Type Mice

AGEs are a heterogeneous group of molecules formed from the nonenzymatic reaction of reducing sugars with free amino groups of proteins, lipids, and/or nucleic acids. AGEs have been shown to play a role in various conditions including cardiovascular disease and diabetes. In this study, we hypothesized that AGEs play a role in the “multiple hit hypothesis” of nonalcoholic fatty liver disease (NAFLD) and contribute to the pathogenesis of hepatosteatosis. We measured the effects of various mouse chows containing high or low AGE in the presence of high or low fat content on mouse weight and epididymal fat pads. We also measured the effects of these chows on the inflammatory response by measuring cytokine levels and myeloperoxidase activity levels on liver supernatants. We observed significant differences in weight gain and epididymal fat pad weights in the high AGE-high fat (HAGE-HF) versus the other groups. Leptin, TNF-α, IL-6, and myeloperoxidase (MPO) levels were significantly higher in the HAGE-HF group. We conclude that a diet containing high AGEs in the presence of high fat induces weight gain and hepatosteatosis in CD-1 mice. This may represent a model to study the role of AGEs in the pathogenesis of hepatosteatosis and steatohepatitis.

Complications during intrahospital transport of critically ill patients: Focus on risk identification and prevention.

Intrahospital transportation of critically ill patients is associated with significant complications. In order to reduce overall risk to the patient, such transports should well organized, efficient, and accompanied by the proper monitoring, equipment, and personnel. Protocols and guidelines for patient transfers should be utilized universally across all healthcare facilities. Care delivered during transport and at the site of diagnostic testing or procedure should be equivalent to the level of care provided in the originating environment. Here we review the most common problems encountered during transport in the hospital setting, including various associated adverse outcomes. Our objective is to make medical practitioners, nurses, and ancillary health care personnel more aware of the potential for various complications that may occur during patient movement from the intensive care unit to other locations within a healthcare facility, focusing on risk reduction and preventive strategies.

Effect of high advanced glycation end-product diet on pulmonary inflammatory response and pulmonary function following gastric aspiration.

ABSTRACT It is not clear why some patients with aspiration advance to acute lung injury or acute respiratory distress syndrome, whereas others do not. The Western diet is high in advanced glycation end-products (AGEs), which have been found to be proinflammatory. We hypothesize that dietary AGEs exaggerate the pulmonary inflammatory response following gastric aspiration. CD-1 mice were randomized to receive either a low-AGE (LAGE) or a high-AGE (HAGE) diet for 4 weeks. Five hours after intratracheal instillation of acidified small gastric particles, pulmonary function was determined. Polymorphonuclear neutrophil counts, albumin, cytokine/chemokine, and tumor necrosis factor soluble receptor II concentrations in the bronchoalveolar lavage and lung myeloperoxidase activity were measured. Compared with LAGE-fed animals, those fed a HAGE diet had increased lung tissue resistance (P = 0.017), bronchoalveolar lavage albumin concentration (P < 0.05), pulmonary polymorphonuclear neutrophil counts (P = 0.0045), and lung myeloperoxidase activity (P = 0.002) following aspiration. In addition, the plasma levels of tumor necrosis factor soluble receptor II were significantly elevated (P < 0.05), whereas paradoxically levels of keratinocyte chemoattractant and monocyte chemoattractant protein 1 were decreased in mice with HAGE diet. In conclusion, a diet high in AGEs exacerbates acute lung injury following gastric aspiration as evidenced by increases in neutrophil infiltration, airway albumin leakage, and decreased pulmonary compliance. This is the first evidence implicating exacerbation of acute inflammatory lung injury by dietary AGEs. Targeting AGEs in the circulatory system may offer a therapeutic strategy for limiting lung injury following gastric aspiration.

Correlation of computed tomographic signs of hypoperfusion and clinical hypoperfusion in adult blunt trauma patients.

BACKGROUND The computed tomographic signs of hypoperfusion (CTSHs) have been reported in radiology literature as preceding the onset of clinical shock in children, but its correlation with tenuous hemodynamic status in adult blunt trauma patients has not been well studied. We hypothesized that these CT findings represent a clinically hypoperfused state and predict patient outcomes. METHODS We retrospectively reviewed 52 adult blunt trauma patients who presented to our Level I trauma center with an Injury Severity Score (ISS) greater than 15 and a systolic blood pressure less than 90 mm Hg and who underwent torso CT scans during a period of 5.5 years. Patient’s demographics and clinical data were recorded. All CT scans were assessed by our radiologist (J.M.) for 25 CTSHs. RESULTS Seventy-nine percent of the patients studied exhibited CTSH. The mean number of signs identified per patient was 4. Patient with the most common CTSH, that is, free peritoneal fluid, small bowel enhancement, flattened inferior vena cava (IVC), and flattened renal veins, had a significantly higher intensive care unit admission rate than those without (all p < 0.05). Patient with signs of small bowel abnormal enhancement/dilation, flattened IVC/renal vein had worse acidosis (all p < 0.05). A significantly lower admission hemoglobin and an increased need for red blood cell transfusion were found in patient with flattened IVC (p < 0.05), flattened renal vein (p < 0.01), and active contrast extravasation (p < 0.01). Univariate analysis identified small bowel dilatation and splenic injury as factors associated with mortality and laparotomy, respectively. Logistic regression model revealed that splenic injury is a significant independent predictor of laparotomy (odd ratio, 7.50; 95% confidence interval, 1.67–33.71; p < 0.01). CONCLUSION CTSH correlates with clinical hypoperfusion in blunt trauma patients and has important prognostic and therapeutic implications. The presence of CTSH in blunt trauma patients should draw immediate attention and require prompt intervention. Trauma surgeons should be familiar with these signs and include them in the clinical decision-making paradigms to improve outcomes in blunt trauma. LEVEL OF EVIDENCE Diagnostic study, level III.

Revisiting endotracheal self-extubation in the surgical and trauma intensive care unit: Are they all fine?

OBJECTIVES Endotracheal self-extubation (ESE) is a serious health care concern. We designed this study to test our hypothesis that not all patients with ESE are successful in spontaneous breathing and reintubation has negative impact on outcomes. METHODS Data on all 39 patients of ESE in our surgical and trauma intensive care unit (ICU) in 2012 were prospectively collected and retrospectively analyzed. RESULTS There were 42 episodes of ESE in 39 of 939 intubated patients (frequency, 4.0%), with 54% of events requiring reintubation. Pre-ESE positive end-expiratory pressure was higher and Pao2/fraction of inspired oxygen ratio was lower, and the post-ESE respiration rate was higher in the reintubated group. On univariate analysis, weaning and spontaneous breathing trial before ESE were favorable predictors for nonreintubation. Multivariate regression analysis demonstrated that agitation before ESE was an independent predictor of reintubation. The need for reintubation was associated with increased risk of pulmonary infectious complications, ventilator days, the need for tracheostomy, and ICU and hospital LOS. The financial costs for ventilator days and ICU rooms were significantly higher in patients with reintubation. CONCLUSION Not all patients were fine after ESE. We have not decreased the frequency of ESE or improved outcomes if the patients were reintubated. The need for reintubation was not only associated with a high pulmonary complication rate but also prolonged duration on mechanical ventilation and hospital/ICU stay and increased the hospital costs.

A seven-center examination of the relationship between monthly volume and mortality in trauma: a hypothesis-generating study

IntroductionThe relationship between trauma volumes and patient outcomes continues to be controversial, with limited data available regarding the effect of month-to-month trauma volume variability on clinical results. This study examines the relationship between monthly trauma volume variations and patient mortality at seven Level I Trauma Centers located in the Eastern United States. We hypothesized that higher monthly trauma volumes may be associated with lower corresponding mortality.MethodsMonthly patient volume data were collected from seven Level I Trauma Centers. Additional information retrieved included monthly mortality, demographics, mean monthly injury severity (ISS), and trauma mechanism (blunt versus penetrating). Mortality was utilized as the primary study outcome. Statistical corrections for mean age, gender distribution, ISS, and mechanism of injury were made using analysis of co-variance (ANCOVA). Center-specific, annually-adjusted median monthly volumes (CSAA-MMV) were calculated to standardize patient volume differences across participating institutions. Statistical significance was set at α < 0.05.ResultsA total of 604 months of trauma admissions, encompassing 122,197 patients, were analyzed. Controlling for patient age, gender, ISS, and mechanism of injury, aggregate data suggested that monthly trauma volumes < 100 were associated with significantly greater mortality (3.9%) than months with volumes > 400 (mortality 2.9%, p < 0.01). To account for differences in monthly volumes between centers, as well as for temporal bias associated with potential differences over the entire study duration period, data were normalized using CSAA-MMV as a standardized reference point. Monthly volumes ≤ 33% of the CSAA-MMV were associated with adjusted mortality of 5.0% whereas monthly volumes ≥ 134% CSAA-MMV were associated with adjusted mortality of 2.7% (p < 0.01).ConclusionsThis hypothesis-generating study suggests that greater monthly trauma volumes appear to be associated with lower mortality. In addition, our data also suggest that across all participating centers mortality may be a function of relative month-to-month volume variation. When normalized to institution-specific, annually-adjusted “median” monthly trauma contacts, we show that months with patient volumes ≤ 33% median may be associated with subtly but not negligibly (1.4–2.3%) higher mortality than months with patient volumes ≥ 134% median.

What's new in academic medicine: Can we effectively address the burnout epidemic in healthcare?

Burnout is a complex syndrome that involves depersonalization (DP), a diminished sense of accomplishment, and emotional exhaustion (EE) [Figure 1].[1‐6] Burnout has become an epidemic that, depending on specialty, is thought to affect between 40% and 60% of practicing physicians [Figure 2].[5‐7] In addition, substantial proportion of physicians in training, at various stages of their education, experience burnout.[2‐6] The authors will demonstrate throughout the current manuscript that burnout is present across all levels of training, specialties, and practice patterns [Figures 2 and 3].[5‐8] Medical education is among the most challenging, stressful, and emotionally taxing experiences.[9] It is therefore not surprising that signs and symptoms of burnout first emerge at this stage, and medical students are susceptible to numerous psychological conditions, from neurotic symptoms to overt depression.[10]

What do we use in the care of adolescent blunt abdominal solid organ injury: guidelines or “mindlines”?

DOI of original article: 10.1016/j.jss.2013.0 * Corresponding author. Division of Trauma Tel.: þ1 716 898 5283; fax: þ1 716 898 5029. E-mail address: waguo@buffalo.edu. 0022-4804/