Metabolomics Pilot Study Identifies Desynchronization of 24-H Rhythms and Distinct Intra-patient Variability Patterns in Critical Illness: A Preliminary Report.

Background: Synchronized circadian rhythms play a key role in coordinating physiologic health. Desynchronized circadian rhythms may predispose individuals to disease or be indicative of underlying disease. Intensive care unit (ICU) patients likely experience desynchronized circadian rhythms due to disruptive environmental conditions in the ICU and underlying pathophysiology. This observational pilot study was undertaken to determine if 24-h rhythms are altered in ICU patients relative to healthy controls by profiling 24-h rhythms in vital signs and plasma metabolites. Methods: We monitored daily rhythms in 5 healthy controls and 5 ICU patients for 24 h. Heart rate and blood pressure were measured every 30 min, temperature was measured every hour, and blood was sampled for mass spectrometry-based plasma metabolomics every 4 h. Bedside sound levels were measured every minute. Twenty-four hours rhythms were evaluated in vitals and putatively identified plasma metabolites individually and in each group using the cosinor method. Results: ICU patient rooms were significantly louder than healthy controls' rooms and average noise levels were above EPA recommendations. Healthy controls generally had significant 24-h rhythms individually and as a group. While a few ICU patients had significant 24-h rhythms in isolated variables, no significant rhythms were identified in ICU patients as a group, except in cortisol. This indicates a lack of coherence in phases and amplitudes among ICU patients. Finally, principal component analysis of metabolic profiles showed surprising patterns in plasma sample clustering. Each ICU patient's samples were clearly discernable in individual clusters, separate from a single cluster of healthy controls. Conclusions: In this pilot study, ICU patients' 24-h rhythms show significant desynchronization compared to healthy controls. Clustering of plasma metabolic profiles suggests that metabolomics could be used to track individual patients' clinical courses longitudinally. Our results show global disordering of metabolism and the circadian system in ICU patients which should be characterized further in order to determine implications for patient care.

Electronically Triggered Sepsis Alert in Non-Intensive Care Inpatients Using Modified Systemic Inflammatory Response Syndrome Criteria: A Retrospective Observational Study with In-Depth Analysis of Surgical Patients.

Background: Our center initiated an electronic Sepsis Best Practice Alert (sBPA) protocol to aid in early sepsis detection and treatment. However, surgery alters peri-operative physiology, which may trigger an sBPA for noninfectious causes. This study aimed to provide early evaluation of automated sBPA utility in surgical patients. Methods: This study was a retrospective review of the outcomes of patients admitted to the University of Minnesota Medical Center (but not to the intensive care unit) from August 2015-March 2016 and compared how the sBPA performed in those having and not having surgery. An sBPA prompted nursing to draw blood for an immediate lactate assay if two modified systemic inflammatory response syndrome (mSIRS) criteria or three mSIRS criteria within 24 hours after surgery were met. Physicians were notified if the lactate concentration was >2 mmol/L. Further review was performed of data collected prospectively on the surgical patients. Results: A total of 10,335 patients were admitted (2,158 surgery and 8,177 non-surgery). Of these, 33% of the surgery patients and 35% of the patients not having surgery triggered sBPAs. In surgery patients, 13% of lactate concentrations were >2 mmol/L versus 25% in patients not having surgery. An sBPA was triggered more frequently after procedures with a wound class of 4 (5% vs. 2%), emergency operation (23% vs. 10%), and longer operations (280 min vs. 222 min (p < 0.05 for all). Surgery patients triggering sBPAs had longer hospital stays (9.6 vs. 4.4 days; p < 0.05), more surgical site infections (7% vs. 2%; p < 0.05), and a similar mortality rate (3% vs. 4%; p = 0.15) than those who did not trigger an sBPA. Conclusion: An sBPA fired in a third of all inpatients, and an sBPA that prompted lactate measurements was less likely to be abnormal in surgery patients than in those not having surgery. There was no difference in the mortality rate in surgical patients who fired and those who did not; however, the sBPA did identify patients with a more complicated post-operative course. Further refinements of the electronic trigger should increase BPA specificity.

ACS/ASE Medical Student Simulation-Based Skills Curriculum Study: Implementation Phase.

OBJECTIVE: Patient safety initiatives have revealed a need for standardized medical student skills curricula. In 2014 the America College of Surgeons/Association for Surgical Education Medical Student Simulation-based Skills Research Collaborative initiated a multisite study to implement and study the effect of a skills curriculum during the surgical clerkship. DESIGN: Students underwent knot-tying and suturing sessions. They performed a self-evaluation survey before and after the modules to assess their comfort level with the skills. Faculty members also evaluated the students at the completion of the skills sessions. The comfort level choices were: needs further review; proficient in simulated setting with assistance; proficient in simulated setting without assistance; and proficient in clinical setting under supervision. RESULTS: At the completion of the modules greater than 99.3% and 98.5% of students reported that they were proficient in knot-tying and suturing, respectively, in either a simulated or clinical environment. Similarly, when faculty evaluated student performance after a session, simulated or clinically proficiency reached over 97% for both two-handed and instrument knot-tying. The faculty rated the students 86.6% proficient for suturing. CONCLUSIONS: After completing the modules, a large percentage of students obtained proficiency in knot-tying and suturing, representing technical skills improvements noted by both the participants and the evaluating faculty. The America College of Surgeons/Association for Surgical Education medical student surgical skills modules represent expert developed, low cost, easy to access resources that should continue to be evaluated and disseminated to medical student learners.

Recanalization of Chronic Extrahepatic Portal Vein Obstruction in Pediatric Patients Using a Minilaparotomy Approach.

PURPOSE: Extrahepatic portal vein obstruction (EHPVO) is the most frequent cause of portal hypertension in children. Some patients are not amenable to meso-Rex bypass and alternative surgeries do not restore physiologic flow. We aim to demonstrate the feasibility and safety of minilaparotomy for recanalization of chronic EHPVO. METHODS: This 2013-2015 single-center, retrospective review included pediatric patients with chronic EHPVO who underwent minilaparotomy, mesenteric vein access, and attempted recanalization of the occluded portal vein. Outcomes included portal patency, resolution of variceal bleeding, size and number of varices, spleen size, and platelet count. RESULTS: There were 6 EHPVO patients. The median age was 9.9 years and median duration of EHPVO was 7 years (3-16 years). EHPVO etiologies were liver transplantation (50%), idiopathic (33%), and umbilical vein catheterization (17%). Four patients (67%) had successful portal vein recanalization and stenting. At last follow-up [median 3.1 years (2.2-4.3 years)] all successfully recanalized patients had patent portal vein stents and resolution of varices and variceal bleeding. The median reduction in spleen size was 26%, with improvement in platelet counts (50-310/µL). The 2 patients with an idiopathic etiology may have never had a main extrahepatic portal vein based on imaging, and both were unable to be recanalized. CONCLUSIONS: Recanalization and stenting of a prolonged occlusion of the portal vein via a minilaparotomy approach is feasible, safe, and may provide an alternative to shunt surgery or endoscopic therapy in selected patients.

D-ß-Hydroxybutyrate and melatonin for treatment of porcine hemorrhagic shock and injury: a melatonin dose-ranging study.

OBJECTIVE: Treatment with a combination of D-ß-hydroxybutyrate (BHB) and melatonin (M) improves survival in hemorrhagic shock models. Our objective was to find the most effective melatonin concentration in combination with 4 molar BHB (4 M BHB). Survival and markers of organ injury were analyzed in pigs exposed to pulmonary contusion, liver crush injury, and hemorrhagic shock and treated with lactated Ringer's solution; 4 M BHB/43 mM M; 4 M BHB/20 mM M; 4 M BHB/10 mM M; 4 M BHB/4.3 mM M; or 4 M BHB/0.43 mM M. This work is an extension of a previously published research study. RESULTS: Survival was highest in pigs receiving 4 M BHB/43 mM M (13/14), followed by lactated Ringer's solution (11/16) and BHB/M with decreased melatonin concentrations (4 M BHB/20 mM M 3/6, 4 M BHB/10 mM M 2/6, 4 M BHB/4.3 mM M 3/6, 4 M BHB/0.43 mM M 1/6, p = 0.011). High mortality was associated with increases in serum lactate, higher liver and muscle injury markers and decreases in PaO2:FiO2 ratios. Our study indicates that treatment with 4 M BHB and melatonin concentrations below 43 mM lack the survival benefit observed from 4 M BHB/43 mM melatonin in pigs experiencing hemorrhagic shock and polytrauma.

Assessment of key plasma metabolites in combat casualties.

BACKGROUND: Previous studies have indicated that hemorrhagic shock and injury cause significant early changes in metabolism. Recently, global changes in metabolism have been described using metabolomics in animal models and civilian trauma. We evaluated metabolic changes associated with combat injury to identify early biomarkers and aid in triage. METHODS: Plasma obtained at emergency department presentation and intervals thereafter from patients injured during combat operations in Iraq (n = 78) were compared with healthy control subjects (n = 40). Using proton Nuclear Magnetic Resonance (NMR), water-soluble metabolites were detected and quantified. Resulting metabolic profiles were analyzed with partial least squares discriminant analysis, Receiver Operating Characteristic (ROC), and cluster analyses to identify features of combat injury and mortality. RESULTS: Significant alterations to metabolism resulted from traumatic injury. Metabolic profiles of injured patients differed from those of healthy controls, driven by increased 5-aminolevulinate and hypoxanthine that persisted through 24 hours. Among combat-injured patients, increased succinate and malonate best discriminated between those who survived from those who did not. Higher levels of succinate and hypoxanthine were associated with increased injury severity. ROC analysis showed that these metabolites had equivalent or superior performance to lactate in distinguishing the presence of trauma, injury severity, and mortality. CONCLUSION: Combat injury is associated with several changes at the metabolic level compared with healthy individuals. Novel potential biomarkers of mortality (succinate, malonate), injury severity (succinate, hypoxanthine), and the presence of trauma (hypoxanthine, 5-aminolevulinate) perform as well as or better than the common clinical standard, lactate. LEVEL OF EVIDENCE: Prognostic study, level III.

Basic airway skills acquisition using the American College of Surgeons/Association for Surgical Education medical student simulation-based surgical skills curriculum: Initial results.

BACKGROUND: The ACS/ASE Medical Student Simulation-Based Skills Curriculum was developed to standardize medical student training. This study aims to evaluate the feasibility and validity of implementing the basic airway curriculum. METHODS: This single-center, prospective study of medical students participating in the basic airway module from 12/2014-3/2016 consisted of didactics, small-group practice, and testing in a simulated clinical scenario. Proficiency was determined by a checklist of skills (1-15), global score (1-5), and letter grade (NR-needs review, PS-proficient in simulation scenario, CP-proficient in clinical scenario). A proportion of students completed pre/post-test surveys regarding experience, satisfaction, comfort, and self-perceived proficiency. RESULTS: Over 16 months, 240 students were enrolled with 98% deemed proficient in a simulated or clinical scenario. Pre/post-test surveys (n = 126) indicated improvement in self-perceived proficiency by 99% of learners. All students felt moderately to very comfortable performing basic airway skills and 94% had moderate to considerable satisfaction after completing the module. CONCLUSIONS: The ACS/ASE Surgical Skills Curriculum is a feasible and effective way to teach medical students basic airway skills using simulation.

Riding into the golden years: injury patterns and outcomes of advanced-age motorcycle trauma.

BACKGROUND: Our objectives were to characterize injury, complications, and outcomes for older riders after motorcycle accidents due to the rising trend in advanced-age motorcyclists. METHODS: From 2008 to 2013, injured motorcyclists were compared by age group: younger (0 to 54 years) vs older (≥55 years) in a retrospective review of the trauma databank at North Memorial Medical Center, a Level-1 trauma center. RESULTS: Of 432 patients, the older group (n = 100) had more fractures (60% vs 42%), injuries per patient (2 vs 1), intensive care unit admissions (48% vs 32%), ventilator days (8 vs 5), in-hospital complications (16% vs 8%), and hospital days (5.5 vs 3) than the younger group (n = 332), P < .01. The older group was also more likely to be discharged to a destination other than home, 35% vs 18%, P < .01. CONCLUSIONS: Older riders are at risk for more severe injury, longer and more complex hospitalizations, and higher care demands after discharge. Both age-specific treatment and care systems will need to evolve to accommodate the needs of the aging trauma population.

Stereotypical Metabolic Response to Endoscopic Retrograde Cholangiopancreatography Show Alterations in Pancreatic Function Regardless of Post-Procedure Pancreatitis.

OBJECTIVES: Metabolomics-based diagnosis or prediction of risk may improve patient outcomes and improve understanding of the pathogenesis of acute pancreatitis (AP). Endoscopic retrograde cholangiopancreatography (ERCP) is a risk factor for developing AP. This pilot study examined metabolomes of patients before and after ERCP, hypothesizing that metabolomics could differentiate between patients who did and did not develop post-ERCP pancreatitis, and that biomarkers associated with development of AP could be identified. METHODS: Patients at high risk for developing post-ERCP pancreatitis were prospectively enrolled at the University of Minnesota from October 2012 to February 2014. Urine and serum samples were collected before ERCP, 2 h after ERCP, and daily thereafter if patients were admitted to the hospital with AP. Pancreatitis severity was calculated with Bedside Index for Severity in Acute Pancreatitis (BISAP) and Modified Glasgow scores. Patients who developed AP (n=9) were matched to patients who did not develop AP (n=18) by age and gender. Urine and serum metabolites were profiled with nuclear magnetic resonance spectroscopy. Partial least squares discriminant analysis (PLS-DA) was performed to detect changes in metabolic profiles associated with development of pancreatitis. Metabolic networks were constructed to probe functional relationships among metabolites. RESULTS: Of the 113 enrolled patients, 9 developed mild AP according to BISAP and modified Glasglow scores. PLS-DA showed common differences between pre- and post-ERCP metabolic profiles in urine and serum regardless of AP status, characterized by increases in serum and urine ketones and serum glucose. Pre-ERCP lipase levels were somewhat elevated in those who went on to develop AP, though this did not reach statistical significance. Metabolic networks differed between patients with AP and those without after ERCP; however, metabolomics did not identify specific prognostic or diagnostic markers of ERCP-induced AP. Aspartate and asparagine were identified as well-connected hubs in post-ERCP serum networks of cases and were correlated with aspartate transaminase (AST) and white blood cell count levels. These features were not evident in controls. Serum aspartate was elevated in AP patients relative to those without AP after ERCP (P=0.03). CONCLUSIONS: In this pilot study, ERCP was found to induce global changes in urine and serum metabolomes indicative of alterations in pancreatic function and insulin resistance. This should be taken into consideration in future research on this topic. Post-ERCP serum metabolic networks indicate functional differences surrounding aspartate metabolism between patients with AP and those without. Further study must be done in larger patient populations to test elevated lipase as a prognostic biomarker associated with risk of developing AP and to examine active metabolic mechanisms at work.

Risk Adjustment for Determining Surgical Site Infection in Colon Surgery: Are All Models Created Equal?

BACKGROUND: Colon surgical site infections (SSIs) are being utilized increasingly as a quality measure for hospital reimbursement and public reporting. The Centers for Medicare and Medicaid Services (CMS) now require reporting of colon SSI, which is entered through the U.S. Centers for Disease Control and Prevention's National Healthcare Safety Network (NHSN). However, the CMS's model for determining expected SSIs uses different risk adjustment variables than does NHSN. We hypothesize that CMS's colon SSI model will predict lower expected infection rates than will NHSN. METHODS: Colon SSI data were reported prospectively to NHSN from 2012-2014 for the six Fairview Hospitals (1,789 colon procedures). We compared expected quarterly SSIs and standardized infection ratios (SIRs) generated by CMS's risk-adjustment model (age and American Society of Anesthesiologist [ASA] classification) vs. NHSN's (age, ASA classification, procedure duration, endoscope [including laparoscope] use, medical school affiliation, hospital bed number, and incision class). RESULTS: The patients with more complex colon SSIs were more likely to be male (60% vs. 44%; p = 0.011), to have contaminated/dirty incisions (21% vs. 10%; p = 0.005), and to have longer operations (235 min vs. 156 min; p < 0.001) and were more likely to be at a medical school-affiliated hospital (53% vs. 40%; p = 0.032). For Fairview Hospitals combined, CMS calculated a lower number of expected quarterly SSIs than did the NHSN (4.58 vs. 5.09 SSIs/quarter; p = 0.002). This difference persisted in a university hospital (727 procedures; 2.08 vs. 2.33; p = 0.002) and a smaller, community-based hospital (565 procedures; 1.31 vs. 1.42; p = 0.002). There were two quarters in which CMS identified Fairview's SIR as an outlier for complex colon SSIs (p = 0.05 and 0.04), whereas NHSN did not (p = 0.06 and 0.06). CONCLUSION: The CMS's current risk-adjustment model using age and ASA classification predicts lower rates of expected colon SSIs than does NHSN. This may lead to financial penalties because of the use of limited risk factors. Further efforts at elucidating appropriate risk adjustment measures without unnecessarily burdening hospitals with expensive data collection are necessary.

Extracorporeal membrane oxygenation credentialing: where do we stand?

BACKGROUND: No guidelines exist for credentialing extracorporeal membrane oxygenation (ECMO) physicians despite variable training backgrounds. We aim to identify national patterns of institutional credentialing for ECMO physicians. METHODS: Program directors from 173 US ECMO centers were surveyed regarding credentialing, recertification, training elements, and barriers. RESULTS: Response rate was 42% (73/173). ECMO credentialing for physicians was required in 66% of responding ECMO centers. Only 57% reported an established institutional ECMO credentialing program. Yearly recertification was required in 16%. Common elements included didactic courses (90%), simulation (73%), and proctored cases (68%). Lack of standardization for credentialing (36%) and too little time (36%) were major barriers to program establishment. No differences were found between small- and large-volume centers with respect to credentialing or recertification. CONCLUSIONS: Not all physicians managing ECMO are credentialed and only about half of US centers have established credentialing programs. Standardization of ECMO credentialing may increase training rates and improve variability in credentialing practices across the United States.