Non-invasive measurement of regional respiratory time constants by electrical impedance tomography in the critically ill patient with acute respiratory distress syndrome

Beim Acute Respiratory Distress Syndrome wird durch die Beatmungstherapie das Lungengewebe geschädigt (Atelektrauma oder Überdehnung). Ein positiv end-exspiratorischen Druckes (PEEP) kann diese zusätzliche Schädigung vermindern. Mit Hilfe der elektrischen Impedanztomographie (EIT) wäre eine Monitoringmethode zur Ermittlung des optimalen PEEP-Wertes anwendbar.12 beatmete und relaxierte lungengesunde Patienten und 20 beatmete und relaxierte Patienten mit ARDS wurden vor, während und nach einem inspiratorischen Drucksprungmanöver ausgehend von einem PEEP-Wert von 0, 8 und 15 cm H2O auf 35 cm H2O und ebenso wie vor, während und nach passiver Exspiration zurück auf das entsprechende PEEP-Niveau mit EIT untersucht. Die dabei gewonnenen Verläufe der relativen Impedanzänderung wurden für die ventralen und dorsalen Lungenbezirke mit Hilfe einer bi-exponentiellen Gleichung gefittet. Die regionalen schnellen und langsamen respiratorischen Zeitkonstanten und die Größe der durch sie charakterisierten Lungenbezirke wurden ebenfalls berechnet. Bei den Patienten mit ARDS konnten im Vergleich zu den lungengesunden Patienten in den ventralen und dorsalen Lungenbezirken signifikant kürzere schnelle und langsame respiratorische Zeitkonstanten gefunden werden. Diese wurden ebenfalls signifikant durch verschiedene PEEP-Einstellungen beeinflusst und zeigten signifikante Unterschiede zwischen ventralen und dorsalen Lungenbezirken innerhalb der jeweiligen Gruppe. Das durch die schnelle respiratorische Zeitkonstante charakterisierte Lungenkompartiment war bei den lungengesunden Patienten im Vergleich zu den Patienten mit ARDS signifikant grösser. Mit EIT ist die bettseitige, strahlungsfreie, nicht-invasive und kontinuierliche Detektion und Quantifikation klinisch relevanter unerwünschter Wirkungen der Beatmungstherapie wie Atelektrauma oder Überdehnung möglich. Die EIT kann eine wertvolle Entscheidungshilfe bei der Wahl der optimalen PEEP-Einstellung liefern.Background: Lung tissue of patients with acute respiratory distress syndrome (ARDS) is heterogeneously damaged and prone to develop atelectasis. During inflation, atelectatic regions may exhibit alveolar recruitment accompanied by prolonged filling with air in contrast to regions with already open alveoli with a fast increase in regional aeration. During deflation, derecruitment of injured regions is possible with ongoing loss in regional aeration. The aim of our study was to assess the dynamics of regional lung aeration in mechanically ventilated patients with ARDS and its dependency on positive end-expiratory pressure (PEEP) using electrical impedance tomography (EIT). Methods: Twelve lung healthy and twenty ARDS patients were examined by EIT during sustained step increases in airway pressure from 0, 8 and 15 cm H2O to 35 cm H2O and during subsequent step decrease to the corresponding PEEP. Regional EIT waveforms in the ventral and dorsal lung regions were fitted to bi-exponential equations. Regional fast and slow respiratory time constants and the sizes of the fast and slow compartments were subsequently calculated. Results: ARDS patients exhibited significantly lower fast and slow time constants than the lung healthy patients in ventral and dorsal regions. The time constants were significantly affected by PEEP and differed between the regions. The size of the fast compartment was significantly lower in ARDS patients than in patients with healthy lung under all studied conditions. Conclusion: These results show that regional lung mechanics can be assessed by EIT. They reflect the lower respiratory system compliance of injured lungs and imply more pronounced regional recruitment and derecruitment in ARDS patients

Enteral versus parenteral nutrition in critically ill patients: an updated systematic review and meta-analysis of randomized controlled trials

Subgroup analysis comparing the effect of enteral versus parenteral nutrition on infectious complications in higher versus lower quality trials (with the median methodological score 7 as cutoff). CI confidence interval, EN enteral nutrition, M-H Mantel-Haenszel test, PN parenteral nutrition. (PDF 87 kb

Epidemiology of intra-abdominal infection and sepsis in critically ill patients: "AbSeS", a multinational observational cohort study and ESICM Trials Group Project.

PURPOSE: To describe the epidemiology of intra-abdominal infection in an international cohort of ICU patients according to a new system that classifies cases according to setting of infection acquisition (community-acquired, early onset hospital-acquired, and late-onset hospital-acquired), anatomical disruption (absent or present with localized or diffuse peritonitis), and severity of disease expression (infection, sepsis, and septic shock). METHODS: We performed a multicenter (n = 309), observational, epidemiological study including adult ICU patients diagnosed with intra-abdominal infection. Risk factors for mortality were assessed by logistic regression analysis. RESULTS: The cohort included 2621 patients. Setting of infection acquisition was community-acquired in 31.6%, early onset hospital-acquired in 25%, and late-onset hospital-acquired in 43.4% of patients. Overall prevalence of antimicrobial resistance was 26.3% and difficult-to-treat resistant Gram-negative bacteria 4.3%, with great variation according to geographic region. No difference in prevalence of antimicrobial resistance was observed according to setting of infection acquisition. Overall mortality was 29.1%. Independent risk factors for mortality included late-onset hospital-acquired infection, diffuse peritonitis, sepsis, septic shock, older age, malnutrition, liver failure, congestive heart failure, antimicrobial resistance (either methicillin-resistant Staphylococcus aureus, vancomycin-resistant enterococci, extended-spectrum beta-lactamase-producing Gram-negative bacteria, or carbapenem-resistant Gram-negative bacteria) and source control failure evidenced by either the need for surgical revision or persistent inflammation. CONCLUSION: This multinational, heterogeneous cohort of ICU patients with intra-abdominal infection revealed that setting of infection acquisition, anatomical disruption, and severity of disease expression are disease-specific phenotypic characteristics associated with outcome, irrespective of the type of infection. Antimicrobial resistance is equally common in community-acquired as in hospital-acquired infection

Nutritional situation for larval Atlantic herring (Clupea harengus L.) in two nursery areas in thewestern Baltic Sea

The Greifswalder Bodden (GWB) is considered to be the most important spawning and nursery area for the western Baltic spring-spawning herring. However, the biotic and abiotic reasons for this are still unclear. Consequently, we investigated larval growth conditions in the GWB and in the Kiel Canal (KC), another nursery and spawning area of Baltic herring. We investigated prey quantity and quality [copepod abundance and essential fatty acid (EFA) concentration] as well as biochemically derived growth rates and fatty acid content of larval herring in spring 2011. A significant correlation between larval growth and larval EFA concentration could be observed in the GWB. The highest growth rates and EFA concentrations in the larval herring coincided with high food quality. Compensating effects of food quality on food quantity and vice versa could be observed in both the GWB and the KC. While larval growth rates in the KC were high early in the season, highest growth rates in the GWB were achieved late in the season. In conclusion, neither area was superior to the other, indicating similar growth conditions for larval herring within the region

DYX1C1 is required for axonemal dynein assembly and ciliary motility

DYX1C1 has been associated with dyslexia and neuronal migration in the developing neocortex. Unexpectedly, we found that deleting exons 2–4 of Dyx1c1 in mice caused a phenotype resembling primary ciliary dyskinesia (PCD), a disorder characterized by chronic airway disease, laterality defects and male infertility. This phenotype was confirmed independently in mice with a Dyx1c1 c.T2A start-codon mutation recovered from an N-ethyl-N-nitrosourea (ENU) mutagenesis screen. Morpholinos targeting dyx1c1 in zebrafish also caused laterality and ciliary motility defects. In humans, we identified recessive loss-of-function DYX1C1 mutations in 12 individuals with PCD. Ultrastructural and immunofluorescence analyses of DYX1C1-mutant motile cilia in mice and humans showed disruptions of outer and inner dynein arms (ODAs and IDAs, respectively). DYX1C1 localizes to the cytoplasm of respiratory epithelial cells, its interactome is enriched for molecular chaperones, and it interacts with the cytoplasmic ODA and IDA assembly factor DNAAF2 (KTU). Thus, we propose that DYX1C1 is a newly identified dynein axonemal assembly factor (DNAAF4)

Hypoxia directed migration of human naïve monocytes is associated with an attenuation of cytokine release: indications for a key role of CCL26

Background!#!Numerous tissue-derived factors have been postulated to be involved in tissue migration of circulating monocytes. The aim of this study was to evaluate whether a defined hypoxic gradient can induce directed migration of naïve human monocytes and to identify responsible autocrine/paracrine factors.!##!Methods!#!Monocytes were isolated from peripheral blood mononuclear cells, transferred into chemotaxis chambers and subjected to a defined oxygen gradient with or without the addition of CCL26. Cell migration was recorded and secretome analyses were performed.!##!Results!#!Cell migration recordings revealed directed migration of monocytes towards the source of hypoxia. Analysis of the monocyte secretome demonstrated a reduced secretion of 70% (19/27) of the analyzed cytokines under hypoxic conditions. The most down-regulated factors were CCL26 (- 99%), CCL1 (- 95%), CX3CL1 (- 95%), CCL17 (- 85%) and XCL1 (- 83%). Administration of recombinant CCL26 abolished the hypoxia-induced directed migration of human monocytes, while the addition of CCL26 under normoxic conditions resulted in a repulsion of monocytes from the source of CCL26.!##!Conclusions!#!Hypoxia induces directed migration of human monocytes in-vitro. Autocrine/paracrine released CCL26 is involved in the hypoxia-mediated monocyte migration and may represent a target molecule for the modulation of monocyte migration in-vivo

Functional Regions of Interest in Electrical Impedance Tomography: A Secondary Analysis of Two Clinical Studies.

INTRODUCTION:Patients with acute respiratory distress syndrome (ARDS) typically show a high degree of ventilation inhomogeneity, which is associated with morbidity and unfavorable outcomes. Electrical impedance tomography (EIT) is able to detect ventilation inhomogeneity, but it is unclear which method for defining the region of interest (ROI) should be used for this purpose. The aim of our study was to compare the functional region of interest (fROI) method to both the lung area estimation method (LAEM) and no ROI when analysing global parameters of ventilation inhomogeneity. We assumed that a good method for ROI determination would lead to a high discriminatory power for ventilation inhomogeneity, as defined by the area under the receiver operating characteristics curve (AUC), comparing patients suffering from ARDS and control patients without pulmonary pathologies. METHODS:We retrospectively analysed EIT data from 24 ARDS patients and 12 control patients without pulmonary pathology. In all patients, a standardized low-flow-pressure volume maneuver had been performed and was used for EIT image generation. We compared the AUC for global inhomogeneity (GI) index and coefficient of variation (CV) between ARDS and control patients using all EIT image pixels, the fROI method and the LAEM for ROI determination. RESULTS:When analysing all EIT image pixels, we found an acceptable AUC both for the GI index (AUC = 0.76; 95% confidence interval (CI) 0.58-0.94) and the CV (AUC = 0.74; 95% CI 0.55-0.92). With the fROI method, we found a deteriorating AUC with increasing threshold criteria. With the LAEM, we found the best AUC both for the GI index (AUC = 0.89; 95% CI 0.78-1.0) and the CV (AUC = 0.89; 95% CI 0.78-1.0) using a threshold criterion of 50% of the maximum tidal impedance change. CONCLUSION:In the assessment of ventilation inhomogeneity with EIT, functional regions of interest obscure the difference between patients with ARDS and control patients without pulmonary pathologies. The LAEM is preferable to the fROI method when assessing ventilation inhomogeneity

Influence of pathogen and focus of infection on procalcitonin values in sepsis patients with bacteremia or candidemia

Abstract Background This study aimed to evaluate the accuracy of procalcitonin (PCT) serum concentrations to diagnose Gram-negative bacteremia and the association of PCT serum concentrations with more specific pathogens and the focus of infection. Methods Secondary analysis of the prospectively collected patient-level dataset from a cluster randomized quality improvement trial was performed. The trial included sepsis patients with organ dysfunction treated in the participating intensive care units from 2011 to 2015. Test performance for the prediction of Gram-negative bacteremia was assessed by receiver operating curve analysis. Independent effects of specific pathogen groups and foci of infection on PCT concentrations were assessed by linear logistic regression models. Results Blood cultures (BC) and PCT concentrations had been taken in 4858 of 6561 documented patients. PCT was significantly higher in Gram-negative bacteremia compared to Gram-positive bacteremia or candidemia (p < 0.001). The area under the curve was 0.72 (95% confidence interval 0.71–0.74) for the prediction of Gram-negative bacteremia compared to all other blood culture results including negative blood cultures. The optimized cutoff value was 10 ng/ml (sensitivity 69%, specificity 35%). PCT differed significantly between specific groups of pathogens (p < 0.001) with highest concentrations in Escherichia coli, Streptococcus species and other Enterobacteriaceae. PCT was highest in urogenital followed by abdominal infection and lowest in respiratory infection (p < 0.001). In a linear regression model, Streptococci, E. coli and other Enterobacteriaceae detected from BC were associated with three times higher PCT values. Urogenital or abdominal foci of infection were associated with twofold increased PCT values independent of the pathogen. Conclusions Serum PCT concentrations are higher in patients with Gram-negative bacteremia than in patients with Gram-positive bacteremia or candidemia. However, the discriminatory power of this difference is too low to guide therapeutic decisions. Variations in PCT serum concentrations are not determined solely by Gram-negative or Gram-positive bacteria but are also affected by distinct groups of pathogens and different foci of infection. Trial registration ClinicalTrials.gov, NCT01187134. Registered on 23 August 2010