Establishment of Predictive Models for Nonocclusive Mesenteric Ischemia Comparing 8,296 Control with 452 Study Patients.

OBJECTIVE: The aim of this study was to develop clinical preoperative, intraoperative, and postoperative scores for early identification of patients who are at risk of nonocclusive mesenteric ischemia (NOMI). DESIGN: A retrospective analysis. SETTING: Single center. PARTICIPANTS: From January 2008 to December 2014, all patients from the Department of Thoracic and Cardiovascular Surgery were included on the basis of the hospital database. INTERVENTIONS: All mesenteric angiographically identified NOMI patients were compared with non-NOMI patients. MEASUREMENTS AND MAIN RESULTS: The study population of 8,748 patients was randomized into a cohort for developing the scores (non-NOMI 4,214 and NOMI 235) and a cohort for control (non-NOMI 4,082 and NOMI 217). Risk factors were identified using forward and backward Wald test and were included in the predictive scores for the occurrence of NOMI. C statistic showed that the scores had a high discrimination for the prediction of NOMI preoperatively (C statistic 0.79; p < 0.001), intraoperatively (C statistic 0.68; p < 0.001), and postoperatively (C statistic 0.85; p < 0.001). A combination of the preoperative, intraoperative, and postoperative risk scores demonstrated the highest discrimination (C statistic 0.87; p < 0.001). The combined score included the following risk factors: renal insufficiency (preoperative); use of cardiopulmonary bypass and intra-aortic balloon pump support (intraoperative); and reexploration for bleeding, renal replacement therapy, and packed red blood cells ≥ 4 units (postoperative). The results were similar in the control group. CONCLUSIONS: These scores could be useful to identify patients at risk for NOMI and promote a rapid diagnosis and therapy.

Presepsin (sCD14-ST) Is a Novel Marker for Risk Stratification in Cardiac Surgery Patients.

BACKGROUND: Presepsin (soluble cluster-of-differentiation 14 subtype [sCD14-ST]) is a humoral risk stratification marker for systemic inflammatory response syndrome and sepsis. It remains unknown whether presepsin can be used to stratify risk in elective cardiac surgery. The authors therefore determined the usefulness of presepsin for risk stratification in patients having elective cardiac surgery. METHODS: Eight hundred fifty-six cardiac surgical patients were prospectively studied. Preoperative plasma concentrations of presepsin, procalcitonin, N-terminal pro-hormone natriuretic peptide, cystatin C, and the additive European System of Cardiac Operative Risk Evaluation 2 were compared to mortality at 30 days (primary outcome), 6 months, and 2 yr. Discrimination was assessed with C statistic. Logistic regression analysis was used to calculate univariable and multivariable odds ratios. RESULTS: Thirty-day mortality was 3.2%, 6-month mortality was 6.1%, and 2-yr mortality was 10.4% across the population. Median preoperative presepsin concentrations were significantly greater in 30-day nonsurvivors than in survivors: 842 pg/ml (interquartile range, 306 to 1,246) versus 160 pg/ml (interquartile range, 122 to 234); difference, 167 pg/ml (interquartile range, 92 to 301; P < 0.001). The results were similar for 6-month and 2-yr mortality. Compared to the European System of Cardiac Operative Risk Evaluation 2, presepsin concentration provided better discrimination for postoperative mortality at all follow-up periods, including 30 days (C statistic 0.88 vs. 0.74), 6 months (0.87 vs. 0.76), and 2 yr (0.81 vs. 0.74). Presepsin also provided better discrimination than cystatin C, N-terminal pro-hormone natriuretic peptide, or procalcitonin. Elevated presepsin remained an independent risk predictor after adjustment for potential confounding factors. CONCLUSIONS: Elevated preoperative plasma presepsin concentration is an independent predictor of postoperative mortality in elective cardiac surgery patients and is a stronger predictor than several other commonly used assessments.

Long-term continuous renal replacement therapy and anticoagulation with citrate in critically ill patients with severe liver dysfunction.

BACKGROUND: As of 2009, anticoagulation with citrate was standard practice in continuous renal replacement therapy (CRRT) for critically ill patients at the University Medical Centre of Saarland, Germany. Partial hepatic metabolism of citrate means accumulation may occur during CRRT in critically ill patients with impaired liver function. The aim of this study was to evaluate the actual influence of hepatic function on citrate-associated complications during long-term CRRT. METHODS: In a retrospective study conducted between January 2009 and November 2012, all cases of dialysis therapy performed in the interdisciplinary surgical intensive care unit were analysed. Inclusion criteria were CRRT and regional anticoagulation with citrate, pronounced liver dysfunction, and pathologically reduced indocyanine green plasma disappearance rate (ICG-PDR). RESULTS: A total of 1339 CRRTs were performed in 69 critically ill patients with liver failure. At admission, the mean Model for End-stage Liver Disease score was 19.2, and the mean ICG-PDR was 9.8%. Eight patients were treated with liver replacement therapy, and 30 underwent transplants. The mortality rate was 40%. The mean duration of dialysis was 19.4 days, and the circuit patency was 62.2 h. Accumulation of citrate was detected indirectly by total serum calcium/ionised serum calcium (tCa/iCa) ratio > 2.4. This was noted in 16 patients (23.2%). Dialysis had not to be discontinued for metabolic disorder or accumulation of citrate in any case. In 26% of cases, metabolic alkalosis occurred with pH > 7.5. Interestingly, no correlation between citrate accumulation and liver function parameters was detected. Moreover, most standard laboratory liver function parameters showed poor predictive capabilities for accumulation of citrate. CONCLUSIONS: Our findings indicate that extra-hepatic metabolism of citrate seems to exist, avoiding in most cases citrate accumulation in critically ill patients despite impaired liver function. Because the citric acid cycle is oxygen-dependent, disturbed microcirculation would result in inadequate citrate metabolism. Raising the tCa/iCa ratio would therefore be an indicator of severity of illness and mortality rather than of liver failure. However, further studies are warranted for confirmation.

Acute kidney injury prediction in cardiac surgery patients by a urinary peptide pattern: a case-control validation study.

BACKGROUND: Acute kidney injury (AKI) is a prominent problem in hospitalized patients and associated with increased morbidity and mortality. Clinical medicine is currently hampered by the lack of accurate and early biomarkers for diagnosis of AKI and the evaluation of the severity of the disease. In 2010, we established a multivariate peptide marker pattern consisting of 20 naturally occurring urinary peptides to screen patients for early signs of renal failure. The current study now aims to evaluate if, in a different study population and potentially various AKI causes, AKI can be detected early and accurately by proteome analysis. METHODS: Urine samples from 60 patients who developed AKI after cardiac surgery were analyzed by capillary electrophoresis-mass spectrometry (CE-MS). The obtained peptide profiles were screened by the AKI peptide marker panel for early signs of AKI. Accuracy of the proteomic model in this patient collective was compared to that based on urinary neutrophil gelatinase-associated lipocalin (NGAL) and kidney injury molecule-1 (KIM-1) ELISA levels. Sixty patients who did not develop AKI served as negative controls. RESULTS: From the 120 patients, 110 were successfully analyzed by CE-MS (59 with AKI, 51 controls). Application of the AKI panel demonstrated an AUC in receiver operating characteristics (ROC) analysis of 0.81 (95 % confidence interval: 0.72-0.88). Compared to the proteomic model, ROC analysis revealed poorer classification accuracy of NGAL and KIM-1 with the respective AUC values being outside the statistical significant range (0.63 for NGAL and 0.57 for KIM-1). CONCLUSIONS: This study gives further proof for the general applicability of our proteomic multimarker model for early and accurate prediction of AKI irrespective of its underlying disease cause.

A single preoperative FGF23 measurement is a strong predictor of outcome in patients undergoing elective cardiac surgery: a prospective observational study.

INTRODUCTION: Several scoring systems have been developed to predict postoperative mortality and complications in patients undergoing cardiac surgery. However, these computer-based calculations are time- and cost-intensive. A simple but highly predictive test for postoperative risk would be of clinical benefit with respect to increasingly scarce hospital resources. We therefore assessed the predictive power of fibroblast growth factor 23 (FGF23) measurement compared with an established scoring system. METHODS: We conducted a prospective interdisciplinary observational study at the Saarland University Medical Centre that included 859 patients undergoing elective cardiac surgery between January 2010 and March 2011 with a median follow-up after discharge of 822 days. We compared a single preoperative measurement of FGF23 as a prognostic tool with the 18 parameters comprising EuroSCORE II with respect to postoperative mortality, acute kidney injury, non-occlusive mesenteric ischemia, clinical course and long-term outcome. RESULTS: Preoperative FGF23 levels were highly predictive of postoperative outcome and complications. The predictive value of FGF23 for mortality in the receiver operating characteristic curve was greater than the EuroSCORE II (area under the curve: 0.800 versus 0.725). Moreover, preoperative FGF23 independently predicted postoperative acute kidney injury and non-occlusive mesenteric ischemia comparably to the EuroSCORE II. Finally, FGF23 was found to be an independent predictor of clinical course parameters, including duration of surgery, ventilation time and length of stay. CONCLUSIONS: In patients undergoing elective cardiac surgery, a simple preoperative FGF23 measurement is a powerful indicator of surgical mortality, postoperative complications and long-term outcome. Its utility compares to the widely used EuroSCORE II.

Mycobacterium fortuitum peritonitis in peritoneal dialysis and its effects on the peritoneum.

Mycobacterium fortuitum peritonitis is a rare complication in patients undergoing continuous ambulatory peritoneal dialysis (CAPD). A 47-year-old patient was admitted to our tertiary hospital because of culture-negative peritonitis with persisting signs of infection despite adequate empirical antibiotic treatment. Although M. fortuitum was detected and the antibiotic regime subsequently amended, catheter removal was inevitable and the dialysis modality converted to hemodialysis (HD). After long-term antibiotic treatment and an additional latency of 4 months without signs of residual infection, reinitiation of CAPD was planned. Explorative laparoscopy prior to catheter reinsertion revealed multiple adhesions within the peritoneal cavity, preventing adequate catheter function. The clinical course of M. fortuitum peritonitis, the need for catheter removal and the description of peritoneal changes are discussed regarding to recent literature.

A novel adaptation of laparoscopic Tenckhoff catheter insertion technique to enhance catheter stability and function in automated peritoneal dialysis.

INTRODUCTION: Automated peritoneal dialysis (APD) normally takes place overnight. Maintaining a stable PD catheter position, independent of body position, omental wrapping or catheter displacement secondary to bowel movements is essential in maintaining effective catheter function. METHODS: We developed a new procedure of catheter placement through combining and adapting several previously described operative techniques including laparoscopic placement of a curled double cuff Tenckhoff catheter with subcutaneous tunneling superior to the rectus sheet, an oblique course through the abdominal wall, deep entry into the pelvic peritoneum and directed placement of the curled tip within the pouch of Douglas. Retrospective analysis of catheter function was conducted, evaluating catheter position, function, complication rate and catheter survival against findings for current insertion techniques described within literature. RESULTS: Between March 2009 and November 2011, 54 patients underwent PD catheter insertion. The observation period was an average of 343 ± 273 days. All patients received abdominal plain film showing optimal catheter position in 89 %. Reported catheter function was very good in 85.2 %, with no or few alarms per week during APD, moderate in 9.3 % with occasional minor dysfunctions (≤ 2 alarms per night), and poor in 5.6 %, with regular alarm disturbance. In one case, primary dysfunction led to catheter replacement. At completion, stable catheter function with occasional minor dysfunction was achieved in 52 of 54 cases. Catheter-related complications (leakage, hydrocele formation, infection and need for replacement) were observed in 14.8 %. At the end of the observation period, 55.6 % of catheters remained in use. Patient dropout occurred through death (18.5 %), renal transplantation (7.4 %), renal recovery (1.9 %), removal secondary to infection or dysfunction (9.3 %) and conversion to HD due to poor dialysis quality (7.4 %). CONCLUSION: The above technique combines and optimises previously described laparoscopic catheter implantation techniques, allowing increased catheter stability resulting in an undisturbed catheter function suitable for APD.

The gap between calculated and actual calcium substitution during citrate anticoagulation in an immobilised patient on renal replacement therapy reflects the extent of bone loss - a case report.

BACKGROUND: Demineralisation and bone density loss during immobilisation are known phenomena. However information concerning the extent of calcium loss during immobilisation remains inconsistent within literature. This may explain why treatment of bone loss and prevention of further demineralisation is often initiated only when spontaneous bone fracture occurred.Continuous renal replacement therapy is commonly utilised in critically ill patients with acute kidney injury requiring RRT. Regional anticoagulation with citrate for CRRT is well-established within the intensive care setting. Due to calcium free dialysate, calcium is eliminated directly as well as indirectly via citrate binding necessitating calcium substitution. In anuric patients declining calcium requirements over time reflect bone calcium liberation secondary to immobilisation. The difference between the expected and actual need for calcium infusion corresponds to calcium release from bone which is particularly impressive in patients exposed to long-term immobilisation and CRRT. We report a dialysis period in excess of 250 days with continuous renal replacement therapy and anticoagulation with citrate. CASE PRESENTATION: We present a 30-year old male with prolonged multisystem organ failure after bilateral lung transplantation, in whom during a period of 254 days the cumulative difference between expected and actual need for calcium infusion was 14.25 mol, representing an estimated calcium loss of about 571 g. Comparison of computed tomographic imaging of the lower thoracic vertebrae over this period depicts a radiographically discernible decrease in bone density from 238 to 52 Hounsfield Units. The first spontaneous fracture occurred after 6 months of immobilisation. Despite subsequent treatment with bisphosphonates and androgen therapy resulting in an increase in bone density to 90 HU a further fracture occurred. CONCLUSION: In immobilised patients receiving CRRT and anticoagulation with citrate, decreasing need for calcium substitution reflects the degree of bone demineralisation corresponding with radiographic assessment of declining bone mineral density. Such a declining need for calcium substitution could be useful in clinical practice highlighting relevant bone loss which results in spontaneous fractures in immobilised critically ill patients.

Total-to-ionized calcium ratio predicts mortality in continuous renal replacement therapy with citrate anticoagulation in critically ill patients.

INTRODUCTION: Regional citrate anticoagulation is safe, feasible and increasingly used in critically ill patients on continuous renal replacement therapy (CRRT). However, in patients with hepatic or multi-organ dysfunction, citrate accumulation may lead to an imbalance of calcium homeostasis. The study aimed at evaluating the incidence and prognostic relevance of an increased total to ionized calcium ratio (T/I Ca(2+) ratio) and its association to hepatic dysfunction. METHODS: We performed a prospective observational study on n = 208 critically ill patients with acute kidney injury (AKI) and necessity for CRRT with regional citrate anticoagulation (CRRT-citrate) between September 2009 and September 2011. Critical illness was estimated by Simplified Acute Physiology Score II; hepatic function was measured with indocyanine green plasma disappearance rate. After achieving a steady state of calcium homeostasis patients were classified into tertiles according to the T/I Ca(2+) ratio (<2.0 versus 2.0 - 2.39 versus ≥ 2.4). RESULTS: The T/I Ca(2+) ratio was determined as an independent predictor for 28-day mortality in critically ill patients with AKI on CRRT-citrate confirmed by receiver operating characteristics and multivariate analysis (Area under the curve 0.94 ± 0.02; p<0.001). A T/I Ca(2+) ratio ≥ 2.4 independently predicted a 33.5-fold (p<0.001) increase in 28-day mortality-rate. There was a significant correlation between the T/I Ca(2+) ratio and the hepatic clearance (p<0.001) and the severity of critical illness (p<0.001). The efficacy and safety of citrate anticoagulation, determined by blood urea nitrogen, mean filter patency and bleeding episodes, were not significantly different between the tertiles. CONCLUSIONS: In patients on CRRT-citrate T/I Ca(2+) ratio is closely related to the clinical outcome and emerged as an independent predictor of 28-day mortality. Larger studies are required to define the cut-off and predictive value for the T/I Ca(2+) ratio. This ratio is associated with hepatic and/or multi-organ dysfunction and therefore an important therapeutic target.

Impact of Renal Replacement Therapy on Mortality in Critically Ill Patients-The Nephrologist's View within an Interdisciplinary Intensive Care Team.

Acute kidney injury (AKI) is a common complication in critically ill patients with an incidence of up to 50% in intensive care patients. The mortality of patients with AKI requiring dialysis in the intensive care unit is up to 50%, especially in the context of sepsis. Different approaches have been undertaken to reduce this high mortality by changing modalities and techniques of renal replacement therapy: an early versus a late start of dialysis, high versus low dialysate flows, intermittent versus continuous dialysis, anticoagulation with citrate or heparin, the use of adsorber or special filters in case of sepsis. Although in smaller studies some of these approaches seemed to have a positive impact on the reduction of mortality, in larger studies these effects could not been reproduced. This raises the question of whether there exists any impact of renal replacement therapy on mortality in critically ill patients-beyond an undeniable impact on uremia, hyperkalemia and/or hypervolemia. Indeed, this is one of the essential challenges of a nephrologist within an interdisciplinary intensive care team: according to the individual situation of a critically ill patient the main indication of dialysis has to be identified and all parameters of dialysis have to be individually chosen with respect to the patient's situation and targeting the main dialysis indication. Such an interdisciplinary and individual approach would probably be able to reduce mortality in critically ill patients with dialysis requiring AKI.

Reconstructing porous structures from FIB-SEM image data: Optimizing sampling scheme and image processing.

Nano-porous materials can be imaged spatially by focused ion beam scanning electron microscopy (FIB-SEM). This method generates a stack of SEM images that has to be segmented (or reconstructed) to serve as basis for structural characterization. To this end, we apply two state-of-the-art algorithms. We study the influence of the original image's voxel size on estimates of morphological characteristics and effective permeabilities. Special attention is paid to analyzing anisotropies due to the FIB-SEM typical anisotropic sampling. Quantitative comparison of morphological descriptors and flow properties of reconstructed data is enabled by the use of synthetic FIB-SEM sets for which a ground truth is available. Moreover, in that case, reconstruction parameters can be chosen optimally, too.

A material stress test study on occurrence of leakage and material failure of peritoneal dialysis (PD) catheters.

Peritonitis is a common complication of peritoneal dialysis (PD). Our root cause analysis allowed to attribute some cases to leakage of the PD catheter. Accordingly, a clinically based stress test study on potential material damage issues of PD catheters was performed, focusing on material damage caused by cleaning, de- and attachment procedures during dialysate changes and on the individual storage methods of PD catheters between dialysate changes. PD catheters were exposed to both chemical stress by repeating dialysate-flow and physical stress simulating de- and connecting, fixation, pressure, flexing, folding etc.-simulating standard clinical daily routine of 8-10 years PD catheter usage. Potentially by normal usage caused damages should be then detected by intraluminal pressure, light- and electron microscopy. The multi-step visual control showed no obvious damages on PD catheters nor any leakage or barrier indulgence. Our tests simulating daily routine usage of PD catheters for several years could not detect any material defects under chemical or physical stress. Hence, we presume that most PD catheter damages, as identified cause for peritonitis in some of our patients, may be due to accidental, unnoticed external damage (e.g. through scissors, while changing dressings) or neglecting PD catheter handling specifications.

Therapeutic apheresis within immune-mediated neurological disorders: dosing and its effectiveness.

Plasma exchange (PE) and immunoadsorption (IA) are standard therapeutic options of immune-mediated neurological disorders. This study evaluates the relation of the relative quantity of applied dose of PE and/ or IA and its achieved therapeutic effectiveness within the treated underlying neurological disorders. In a retrospective study, we evaluated data from PE and IA carried out 09/2009-06/2014 in neurological patients at the University-Hospital of Saarland, Germany. Apheresis dose was defined as the ratio of the extracorporeal treated plasma volume to the patient's plasma volume. Effectiveness was assessed through disease-specific tests and scores by the attending neurologist(s); results were classified into response or no response. 1101 apheresis (PE:238, IA:863), in 153 hospital-stays were carried out, averaged, 7.0 treatments per patients, 82% responded, 18% not. Mean applied apheresis dose per treatment was 0.91 with mean doses of 1.16 for PE and 0.81 for IA. The totally applied mean dose per stay was 5.6 (PE:5.01, IA:5.81). No correlation was seen between apheresis dosing and treatment effectiveness (PE:R2 = 0.074, IA:R2 = 0.0023). PE and IA in therapy-refractory immune-mediated neurological disorders majorly achieved a measurable severity improvement - without correlation to the applied dose. Moreover, our data rather suggest, that effectiveness may be given with volumes below currently recommended volumes.

Bleeding complications after cardiac surgery, before anticoagulation start and then with argatroban or heparin in the early postoperative setting.

OBJECTIVES: After elective cardiac surgery a postoperative anticoagulation is obligatory. With critically ill patients the conventional anticoagulation standard heparin is sometimes impossible, e.g. based on HIT II. Then, argatroban is currently a possible alternative, however, due to its impaired metabolism in critically ill patients, anticoagulation effect is harder to anticipate, thus resulting in higher bleeding risk. Furthermore, to date no antidote is available. Hence, severe postoperative bleeding incidents under anticoagulation are commonly mono-causal attributed to the anticoagulation itself. This study concentrates on the number of well-defined postoperative bleeding incidents before any anticoagulation started, then actually under argatroban as well as compared to those under heparin (or switched from heparin to argatroban). MATERIAL AND METHODS: Retrospective study including 215 patients undergoing elective cardiac surgery with a postoperative stay in ICU ≥48 h. Postoperative bleeding complications before and after start of anticoagulation were evaluated. Definition of bleeding complications were: decrease of hemoglobin by more than 2 g/dl without dilution (mean value of volume balance plus one standard deviation) and/or increased need of red blood cell transfusion/day (average transfusion rate + 2 standard deviations). RESULTS: Within the study group of 215 patients, 143 were treated with heparin, 43 with argatroban, 29 switched from heparin to argatroban. Overall, 26.5% (57/215) postoperative bleeding complications occurred. In 54.4% (31/57) bleeding complications occurred before start of anticoagulation; in 43.6% (26/57) after. Of these, 14 bleeding incidents occurred under heparin 9.8% (14/143), 6 under argatroban 14% (6/43) and 6 switched 20.7% (6/29). Higher bleeding complications before start of anticoagulation was related to concomitant factors influencing the overall bleeding risk; e.g. score of severity of illness. These observations further correlate with postoperative, but not anticoagulation induced mortality rate of 2.8% of then given heparin, 20.9% then argatroban, 20.7% then switched. CONCLUSIONS: Postoperative bleeding complications cannot simply be attributed to anticoagulation since occurring often before anticoagulation was started. The risk for bleeding complications after start of anticoagulation was quite comparable for argatroban and heparin. Accordingly, the influence of argatroban on bleeding complications in the postoperative period may be less significant than previously thought.

High Serum Bilirubin Levels, NT-pro-BNP, and Lactate Predict Mortality in Long-Term, Severely Ill Respiratory ECMO Patients.

Mortality in patients treated with extracorporeal membrane oxygenation (ECMO) is high. Therefore, it is crucial to better understand conditions that are associated with mortality in ECMO patients. In this retrospective analysis, we observed 51 patients treated with high-flow ECMO in 2013 and 2014 at our center. We recorded laboratory values and intensive care procedures. The hypothesis of bilirubin being a predictor of mortality during ECMO treatment was initially addressed. Therefore, laboratory values were obtained before initiation and at the time of highest bilirubin throughout the procedure. Receiver operating characteristic (ROC) curves and survival analysis were conducted. Our cohort consisted of patients with advanced age (median: 55 years; range: 22-76) and high mortality (26/51; 51%). Lactate, bilirubin, and NT-pro-BNP were significantly (p < 0.05) associated with mortality in univariable analyses. The cut-off values with highest Youden's index were bilirubin ≥10 mg/dl, lactate ≥2.25 mmol/L, and NT-pro-BNP ≥11,500 pg/ml. A multivariable analysis, revealed an area under the curve (AUC) of 0.85 (95% confidence interval [CI]: 0.74-0.97), sensitivity of 0.79, and specificity of 0.91. Bilirubin, lactate, and NT-pro-BNP were associated with mortality during ECMO treatment. However, laboratory values were only evaluated at the time of peak bilirubin.

Proteomics and Metabolomics for AKI Diagnosis.

Acute kidney injury (AKI) is a severe and frequent condition in hospitalized patients. Currently, no efficient therapy of AKI is available. Therefore, efforts focus on early prevention and potentially early initiation of renal replacement therapy to improve the outcome in AKI. The detection of AKI in hospitalized patients implies the need for early, accurate, robust, and easily accessible biomarkers of AKI evolution and outcome prediction because only a narrow window exists to implement the earlier-described measures. Even more challenging is the multifactorial origin of AKI and the fact that the changes of molecular expression induced by AKI are difficult to distinguish from those of the diseases associated or causing AKI as shock or sepsis. During the past decade, a considerable number of protein biomarkers for AKI have been described and we expect from recent advances in the field of omics technologies that this number will increase further in the future and be extended to other sorts of biomolecules, such as RNAs, lipids, and metabolites. However, most of these biomarkers are poorly defined by their AKI-associated molecular context. In this review, we describe the state-of-the-art tissue and biofluid proteomic and metabolomic technologies and new bioinformatics approaches for proteomic and metabolomic pathway and molecular interaction analysis. In the second part of the review, we focus on AKI-associated proteomic and metabolomic biomarkers and briefly outline their pathophysiological context in AKI.

Occurrence and severity of non-occlusive mesenteric ischemia (NOMI) after cardiovascular surgery correlate with preoperatively assessed FGF-23 levels.

PURPOSE: To evaluate the value of preoperatively assessed fibroblast growth factor 23 (FGF-23) levels and to correlate FGF-23 with angiographic findings in non-occlusive mesenteric (NOMI) ischemia using a standardized scoring system. MATERIALS AND METHODS: Between 2/2011 and 3/2012 a total of 865 patients (median age: 67 years) underwent cardiovascular surgery during this ethics committee approved, prospective study. 65 of these patients had clinical suspicion of NOMI and consequently underwent catheter angiography of the superior mesenteric artery. Images were assessed using a standardized reporting system (Homburg-NOMI-Score). These data were correlated to following preoperative parameters of kidney function: cystatin C, creatinine, FGF-23 and estimated glomerular filtration rate (eGFR), and outcome data (death, acute renal failure) using linear and logistic regressions, as well as nonparametric tests. RESULTS: Significant correlations were found between FGF-23 and the angiographic appearance of NOMI (p = 0.03). Linear regression analysis showed no significant correlation to the severity of NOMI with creatinine (p = 0.273), cystatin C (p = 0.484), cystatin C eGFR (p = 0.914) and creatinine eGFR (p = 0.380). Logistic regression revealed a significant correlation between death and the Homburg-NOMI-Score (p<0.001), but not between development of NOMI and acute renal failure (p = 0.122). The ROC Analysis yielded an area under the curve of 0.695 (95% CI: 0.627-0.763) with a sensitivity of 0.672 and specificity of 0.658. CONCLUSIONS: FGF-23 significantly correlates with the severity of NOMI, which is in contrast to other renal function parameters. The applied scoring system allows to predict mortality in NOMI patients.

Prognostic value of procalcitonin in patients after elective cardiac surgery: a prospective cohort study.

BACKGROUND: Procalcitonin (PCT) is a well-known prognostic marker after elective cardiac surgery. However, the impact of elevated PCT in patients with an initially uneventful postoperative course is still unclear. The aim of this study was to evaluate PCT levels as a prognostic tool for delayed complications after elective cardiac surgery. METHODS: A prospective study was performed in 751 patients with an apparently uneventful postoperative course within the first 24 h after elective cardiac surgery. Serum PCT concentration was taken the morning after surgery. All patients were screened for the occurrence of delayed complications. Delayed complications were defined by in-hospital death, intensive care unit readmission, or prolonged length of hospital stay (>12 days). Odds ratios (OR) [with 95% confidence interval (CI)] were calculated by logistic regression analyses and adjusted for confounders. Predictive capacity of PCT for delayed complications was calculated by ROC analyses. The cutoff value of PCT was derived from the Youden Index calculation. RESULTS: Among 751 patients with an initially uneventful postoperative course, 117 patients developed delayed complications. Serum PCT levels the first postoperative day were significantly higher in these 117 patients (8.9 ng/ml) compared to the remaining 634 (0.9 ng/ml; p < 0.001). ROC analyses showed that PCT had a high accuracy to predict delayed complications (optimal cutoff value of 2.95 ng/ml, AUC of 0.90, sensitivity 73% and specificity 97%). Patients with PCT levels above 2.95 ng/ml the first postoperative day had a highly increased risk of delayed complications (adjusted OR, 110.2; 95% CI 51.5-235.5; p < 0.001). CONCLUSIONS: A single measurement of PCT seems to be a useful tool to identify patients at risk of delayed complications despite an initially uneventful postoperative course.

Vasopressin as Therapy During Nonocclusive Mesenteric Ischemia.

BACKGROUND: Vasopressin is used as an adjunct to norepinephrine to support blood pressure in vasodilatory shock after cardiopulmonary bypass (CPB). In this study, we report our observation of vasopressin treatment in 11 patients with nonocclusive mesenteric ischemia (NOMI). METHODS: In an observational cohort study, 78 patients were studied after having been treated for NOMI with intraarterial iloprost infusion after elective cardiac operation. All patients received norepinephrine as vasopressor for marked vasodilation. In 11 patients mean arterial pressure could not be maintained with norepinephrine alone (≤0.4 µg · kg(-1) · min(-1)), and vasopressin was given in addition to norepinephrine as a rescue therapy. The 11 patients (Vaso) and the remaining 67 patients (Nor) were analyzed for clinical improvement after initiation of NOMI treatment, on the following days 1 and 2, and for hospital survival. Intestinal perfusion was controlled by mesenteric angiography. RESULTS: Before initiation of NOMI treatment Vaso patients had significantly higher doses of norepinephrine than the Nor patients (Vaso, 0.65 ± 0.20 µg · kg(-1) · min(-1); Nor, 0.20 ± 0.13 µg · kg(-1) · min(-1); p < 0.001), and their diagnostic score of the angiography was higher (Vaso, 5.4 ± 1.1 points; Nor, 3.5 ± 2.1 points; p = 0.004). After 2 days of NOMI treatment, Vaso patients had improved intestinal perfusion in the control angiography (Vaso, 3.8 ± 1.5 points) and significantly lower doses of norepinephrine than the Nor patients (Vaso, 0.28 ± 0.12 µg · kg(-1) · min(-1); Nor, 0.53 ± 0.34 µg · kg(-1) · min(-1); p = 0.002). All patients survived in the Vaso group; in the Nor group, 17 of 67 patients died in the hospital. CONCLUSIONS: Vasopressin administration during NOMI treatment after CPB seems to improve small intestine perfusion and appears be to associated with improved hospital survival.

Elevated endothelin-1 level is a risk factor for nonocclusive mesenteric ischemia.

OBJECTIVE: Nonocclusive mesenteric ischemia may occur after cardiac surgery, commonly in conjunction with the use of cardiopulmonary bypass. Some evidence suggests that endothelin-1 serum levels are increased in patients with mesenteric ischemia, but the association of endothelin-1 and nonocclusive mesenteric ischemia has not been studied. The objective was to investigate whether elevated levels of endothelin-1 could be found in patients exhibiting nonocclusive mesenteric ischemia. METHODS: In an observational cohort study, nonocclusive mesenteric ischemia developed in 78 of 865 patients undergoing elective cardiac surgery. Control patients were identified from the cohort through 1:1 propensity score matching. Preoperative and postoperative endothelin-1 serum levels were determined by means of enzyme-linked immunosorbent assay. Odds ratios (with 95% confidence interval) were calculated by logistic regression analyses to determine the risk of endothelin-1 for the development of nonocclusive mesenteric ischemia. RESULTS: Patients with nonocclusive mesenteric ischemia had higher preoperative (11.3 vs 9.3 pg/mL; P = .001) and postoperative (15.7 vs 11.1 pg/mL, P < .001) levels of endothelin-1 than the controls. The probability of developing nonocclusive mesenteric ischemia increased with each picogram/milliliter endothelin-1 level preoperatively (odds ratio, 1.29; 95% confidence interval, 1.12-1.49) and each picogram/milliliter postoperatively (odds ratio, 2.04; 95% confidence interval, 1.54-2.72). Receiver operating characteristic analyses showed that elevated endothelin-1 serum levels had a high accuracy to predict nonocclusive mesenteric ischemia (optimal cutoff value of 14.5 pg/mL, area under the curve of 0.77, sensitivity 51%, and specificity 94%). CONCLUSIONS: Endothelin-1 seems to predispose patients undergoing cardiac surgery to develop nonocclusive mesenteric ischemia. In addition, it may be a useful marker to identify patients at risk for nonocclusive mesenteric ischemia after cardiac surgery.