Wearable pulmonary monitoring system with integrated functional lung imaging and chest sound recording: a clinical investigation in healthy subjects.

Objective.Current wearable respiratory monitoring devices provide a basic assessment of the breathing pattern of the examined subjects. More complex monitoring is needed for healthcare applications in patients with lung diseases. A multi-sensor vest allowing continuous lung imaging by electrical impedance tomography (EIT) and auscultation at six chest locations was developed for such advanced application. The aims of our study were to determine the vest's capacity to record the intended bio-signals, its safety and the comfort of wearing in a first clinical investigation in healthy adult subjects.Approach.Twenty subjects (age range: 23-65 years) were studied while wearing the vests during a 14-step study protocol comprising phases of quiet and deep breathing, slow and forced full expiration manoeuvres, coughing, breath-holding in seated and three horizontal postures. EIT, chest sound and accelerometer signals were streamed to a tablet using a dedicated application and uploaded to a back-end server. The subjects filled in a questionnaire on the vest properties using a Likert scale.Main results.All subjects completed the full protocol. Good to excellent EIT waveforms and functional EIT images were obtained in 89% of the subjects. Breathing pattern and posture dependent changes in ventilation distribution were properly detected by EIT. Chest sounds were recorded in all subjects. Detection of audible heart sounds was feasible in 44%-67% of the subjects, depending on the sensor location. Accelerometry correctly identified the posture in all subjects. The vests were safe and their properties positively rated, thermal and tactile properties achieved the highest scores.Significance.The functionality and safety of the studied wearable multi-sensor vest and the high level of its acceptance by the study participants were confirmed. Availability of personalized vests might further advance its performance by improving the sensor-skin contact.

Advancing FDSTools by integrating STRNaming 1.1.

The introduction of massively parallel sequencing in forensic analysis has been facilitated with typing kits, analysis software and allele naming tools such as the ForenSeq DNA Signature Prep (DSP) kit, FDSTools and STRNaming respectively. Here we describe how FDSTools 2.0 with integrated and refined STRNaming nomenclature was validated for implementation under ISO 17025 accreditation for the ForenSeq DSP kit. Newly-added options result in efficient automatic allele calling for the majority of markers while specific settings are applied for 'novel' sequence variants to avoid the calling of remaining variable noise observed in samples sequenced with the ForenSeq DSP kit that seem to arise in the PCR. Genome-wide built-in reference data allows for greatly simplified configuration of allele naming for human targets.

Identification and analysis of stable breathing periods in electrical impedance tomography recordings.

Objective. In this paper, an automated stable tidal breathing period (STBP) identification method based on processing electrical impedance tomography (EIT) waveforms is proposed and the possibility of detecting and identifying such periods using EIT waveforms is analyzed. In wearable chest EIT, patients breathe spontaneously, and therefore, their breathing pattern might not be stable. Since most of the EIT feature extraction methods are applied to STBPs, this renders their automatic identification of central importance.Approach. The EIT frame sequence is reconstructed from the raw EIT recordings and the raw global impedance waveform (GIW) is computed. Next, the respiratory component of the raw GIW is extracted and processed for the automatic respiratory cycle (breath) extraction and their subsequent grouping into STBPs.Main results. We suggest three criteria for the identification of STBPs, namely, the coefficient of variation of (i) breath tidal volume, (ii) breath duration and (iii) end-expiratory impedance. The total number of true STBPs identified by the proposed method was 294 out of 318 identified by the expert corresponding to accuracy over 90%. Specific activities such as speaking, eating and arm elevation are identified as sources of false positives and their discrimination is discussed.Significance. Simple and computationally efficient STBP detection and identification is a highly desirable component in the EIT processing pipeline. Our study implies that it is feasible, however, the determination of its limits is necessary in order to consider the implementation of more advanced and computationally demanding approaches such as deep learning and fusion with data from other wearable sensors such as accelerometers and microphones.

Regional lung function measures determined by electrical impedance tomography during repetitive ventilation manoeuvres in patients with COPD.

OBJECTIVE: Current standards for conducting spirometry examinations recommend that the ventilation manoeuvres needed in pulmonary function testing are carried out repeatedly during sessions. Chest electrical impedance tomography (EIT) can determine the presence of ventilation heterogeneity during such manoeuvres, which increases the information content derived from such examinations. The aim of this study was to characterise regional lung function in patients with chronic obstructive pulmonary disease (COPD) during repetitive forced full ventilation manoeuvres. Regional lung function measures derived from these manoeuvres were compared with quiet tidal breathing. APPROACH: Sixty hospitalised patients were examined during up to three repeated ventilation manoeuvres. Acceptable spirometry manoeuvres were performed and EIT recordings suitable for analysis obtained in 53 patients (12 women, 41 men; age: 68 ± 12 years (mean ± SD)). Pixel values of tidal volume, forced full inspiratory and expiratory volume in 1 s, and forced inspiratory and expiratory vital capacity were calculated from the EIT data. Spatial ventilation heterogeneity was assessed using the coefficient of variation, global inhomogeneity index, and centres and regional fractions of ventilation. Temporal inhomogeneity was determined by examining the pixel expiration times needed to exhale 50% and 75% of regional forced vital capacity. MAIN RESULTS: All EIT-derived measures of regional lung function showed reproducible results during repetitive examinations. Parameters of spatial heterogeneity obtained from quiet tidal breathing were comparable with the measures derived from the forced manoeuvres. SIGNIFICANCE: Measures of spatial and temporal ventilation heterogeneity obtained in COPD patients by EIT provide comparable findings during repeated examinations within one testing session. Quiet tidal breathing generates similar information on ventilation heterogeneity as forced manoeuvres that demand a high amount of patient effort.

[Ultrasound visualization of the guidewire and positioning of the central venous catheter : A prospective observational study]. / Sonographische Visualisierung des Führungsdrahtes und Positionierung des zentralen Venenkatheters : Eine prospektive Beobachtungsstudie.

BACKGROUND: After insertion of a central venous catheter (CVC) the catheter position must be controlled and a pneumothorax ruled out. OBJECTIVE: The aim was to examine whether the use of two standard acoustic windows known from emergency sonography examination techniques is feasible to 1) verify the correct intravenous localization and direction of the guidewire before final CVC insertion and 2) correctly predict the required CVC length for positioning of the catheter tip in the lower third of the superior vena cava. MATERIAL AND METHODS: This single center prospective observational study included adult patients (age ≥18 years) with an indication for CVC insertion after institutional ethics approval was obtained. Puncture sites were restricted to bilateral internal jugular and subclavian veins and except for duplicate examinations no further exclusion criteria were defined. After vessel puncture and insertion of the guidewire, the vena cava was displayed by an additional ultrasound examiner (sector scanner 1.5-3.6 MHz) using the transhepatic or subcostal acoustic window to localize the guidewire. For positioning of the CVC tip, the required catheter length in relation to the cavoatrial junction was measured using the guidewire marks during slow retraction and consecutive disappearance of the J­shaped guidewire tip from each acoustic window. From the resulting insertion length of the guidewire 4 cm was subtracted for the transhepatic and 2 cm for the subcostal window under the assumption that this length correlates to the distance from the cavoatrial junction. The CVC was finally inserted and a chest radiograph was performed for radiological verification of the CVC position. RESULTS: Of 100 included patients, 94 could finally be analyzed. The guidewire could be identified in the vena cava in 91 patients (97%) within a time period of 2.2 ± 1.9 min. In three patients, the wire could not be visualized, although two catheters had the correct position, while one catheter was incorrectly positioned in the opposite axillary vein. In the second study part, positioning of the CVC was evaluated in 44 of the 94 patients. In 5 of these 44 patients, the correct direction and disappearance of the guidewire from the acoustic window could also be reliably visualized; however, with the left subclavian vein as the puncture site, the respective catheters were up to 6 cm too short for correct positioning. Thus, these 5 patients were excluded from this analysis. In the remaining 39 patients, the position of the CVC tip was optimally located in the lower third of the superior vena cava according to the chest radiograph in 20 patients (51%), while it was relatively too high in 5 patients (13%) and too low (entrance of the right atrium) in 9 patients. In the other 5 patients, disappearance of the guidewire from the acoustic window was not definitely detectable. CONCLUSION: The presented intraprocedural ultrasound-based method using two standard acoustic windows is reliable for verification of the correct intravenous location and direction of the guidewire even before dilatation of the vessel puncture site for insertion of the catheter. Furthermore, the method allows the clinically acceptable measurement of the required length for catheter positioning. A chest radiograph can be waived provided the ultrasound examination (identification of the guidewire and exclusion of puncture-related complications such as pneumothorax) is unambiguous.

The Impact of Immersion on Cluster Identification Tasks.

Recent developments in technology encourage the use of head-mounted displays (HMDs) as a medium to explore visualizations in virtual realities (VRs). VR environments (VREs) enable new, more immersive visualization design spaces compared to traditional computer screens. Previous studies in different domains, such as medicine, psychology, and geology, report a positive effect of immersion, e.g., on learning performance or phobia treatment effectiveness. Our work presented in this paper assesses the applicability of those findings to a common task from the information visualization (InfoVis) domain. We conducted a quantitative user study to investigate the impact of immersion on cluster identification tasks in scatterplot visualizations. The main experiment was carried out with 18 participants in a within-subjects setting using four different visualizations, (1) a 2D scatterplot matrix on a screen, (2) a 3D scatterplot on a screen, (3) a 3D scatterplot miniature in a VRE and (4) a fully immersive 3D scatterplot in a VRE. The four visualization design spaces vary in their level of immersion, as shown in a supplementary study. The results of our main study indicate that task performance differs between the investigated visualization design spaces in terms of accuracy, efficiency, memorability, sense of orientation, and user preference. In particular, the 2D visualization on the screen performed worse compared to the 3D visualizations with regard to the measured variables. The study shows that an increased level of immersion can be a substantial benefit in the context of 3D data and cluster detection.

Current clinical use of intravenous fosfomycin in ICU patients in two European countries.

PURPOSE: In Europe, intravenous fosfomycin (IV) is used particularly in difficult-to-treat or complex infections, caused by both Gram-positive and Gram-negative pathogens including multidrug-resistant strains. Here, we investigated the efficacy and safety of intravenous fosfomycin under real-life conditions. METHODS: Prospective, multi-center, and non-interventional study in patients with bacterial infections from 20 intensive care units (ICU) in Germany and Austria (NCT01173575). RESULTS: Overall, 209 patients were included (77 females, 132 males, mean age: 59 ± 16 years), 194 of which were treated in intensive care (APACHE II score at the beginning of fosfomycin therapy: 23 ± 8). Main indications (± bacteremia or sepsis) were infections of the CNS (21.5%), community- (CAP) and hospital-acquired pneumonia (HAP)/ventilator-associated pneumonia (VAP, 15.3%), bone and joint infections (BJI, 11%), abdominal infections (11%), and bacteremia (10.5%). Most frequently identified pathogens were S. aureus (22.3%), S. epidermidis (14.2%), Enterococcus spp. (10.8%), E. coli (12.3%) and Klebsiella spp. (7.7%). At least one multidrug-resistant (MDR) pathogen was isolated from 51 patients (24.4%). Fosfomycin was administered with an average daily dose of 13.7 ± 3.5 g over 12.4 ± 8.6 days, almost exclusively (99%) in combination with other antibiotics. The overall clinical success was favorable in 81.3% (148/182) of cases, and in 84.8% (39/46) of patients with ≥ 1 MDR pathogen. Noteworthy, 16.3% (34/209) of patients developed at least one, in the majority of cases non-serious, adverse drug reaction during fosfomycin therapy. CONCLUSION: Our data suggest that IV fosfomycin is an effective and safe combination partner for the treatment of a broad spectrum of severe bacterial infections in critically ill patients.

Characteristic pattern of pleural effusion in electrical impedance tomography images of critically ill patients.

BACKGROUND: Electrical impedance tomography (EIT) is increasingly used for continuous monitoring of ventilation in intensive care patients. Clinical observations in patients with pleural effusion show an increase in out-of-phase impedance changes. We hypothesised that out-of-phase impedance changes are a typical EIT finding in patients with pleural effusion and could be useful in its detection. METHODS: We conducted a prospective observational study in intensive care unit patients with and without pleural effusion. In patients with pleural effusion, EIT data were recorded before, during, and after unilateral drainage of pleural effusion. In patients with no pleural effusion, EIT data were recorded without any intervention. EIT images were separated into four quadrants of equal size. We analysed the sum of out-of-phase impedance changes in the affected quadrant in patients with pleural effusion before, during, and after drainage and compared it with the sum of out-of-phase impedance changes in the dorsal quadrants of patients without pleural effusion. RESULTS: We included 20 patients with pleural effusion and 10 patients without pleural effusion. The median sum of out-of-phase impedance changes was 70 (interquartile range 49-119) arbitrary units (a.u.) in patients with pleural effusion before drainage, 25 (12-46) a.u. after drainage (P<0.0001) and 11 (6-17) a.u. in patients without pleural effusion (P<0.0001 vs pleural effusion before drainage). The area under the receiver operating characteristics curve was 0.96 (95% limits of agreement 0.91-1.01) between patients with pleural effusion before drainage and those without pleural effusion. CONCLUSIONS: In patients monitored with EIT, the presence of out-of-phase impedance changes is highly suspicious of pleural effusion and should trigger further examination.

No evidence of hepatitis B virus reactivation in patients with resolved infection treated with direct-acting antivirals for hepatitis C in a large real-world cohort.

BACKGROUND: Hepatitis B virus (HBV) reactivation has been observed following interferon (IFN)-based treatment in HBV/hepatitis C virus (HCV) co-infected patients. Recent reports suggest that reactivation may also occur in both hepatitis B surface antigen (HBsAg)-positive and HBsAg-negative patients during HCV treatment with direct-acting antivirals (DAAs). AIM: To investigate the rate of patients with HBV reactivation during IFN-based and IFN-free HCV treatment in a large real-world cohort. METHODS: A total of 848 patients with chronic hepatitis C were treated with different combinations of DAAs. Among patients with available outcome and HBV data, there were 272 patients hepatitis B core antibody (HBcAb)-positive (HBsAg-positive, n=9; HBsAg-negative, n=263), and 536 were HBcAb-negative. All HBcAb-positive patients were tested for HBV DNA at the end of DAA therapy and alanine transaminase (ALT) levels were frequently measured during therapy and follow-up. RESULTS: Seventy-three percent (n=192/263) of HBsAg-negative/HBcAb-positive patients had elevated ALT levels at baseline, which declined to normal values in all but 18 patients, and no HBV reactivation was observed. Eight patients had detectable but not quantifiable HBV DNA (<20 IU/mL) at end of treatment, but none were associated with elevated ALT. Five of nine HBsAg-positive/HBcAb-positive patients experienced transient or permanent HBV reactivation, three of whom required nucleos(t)ide treatment during (n=1) or after (n=2) DAA therapy. CONCLUSIONS: HBV reactivation was not observed in HBsAg-negative/HBcAb-positive patients but common in HBsAg-positive/HBcAb-positive patients treated with different combinations of DAAs for HCV.

Global and regional assessment of sustained inflation pressure-volume curves in patients with acute respiratory distress syndrome.

OBJECTIVE: Static or quasi-static pressure-volume (P-V ) curves can be used to determine the lung mechanical properties of patients suffering from acute respiratory distress syndrome (ARDS). According to the traditional interpretation, lung recruitment occurs mainly below the lower point of maximum curvature (LPMC) of the inflation P-V curve. Although some studies have questioned this assumption, setting of positive end-expiratory pressure 2 cmH2O above the LPMC was part of a 'lung-protective' ventilation strategy successfully applied in several clinical trials. The aim of our study was to quantify the amount of unrecruited lung at different clinically relevant points of the P-V curve. APPROACH: P-V curves and electrical impedance tomography (EIT) data from 30 ARDS patients were analysed. We determined the regional opening pressures for every EIT image pixel and fitted the global P-V curves to five sigmoid model equations to determine the LPMC, inflection point (IP) and upper point of maximal curvature (UPMC). Points of maximal curvature and IP were compared between the models by one-way analysis of variance (ANOVA). The percentages of lung pixels remaining closed ('unrecruited lung') at LPMC, IP and UPMC were calculated from the number of lung pixels exhibiting regional opening pressures higher than LPMC, IP and UPMC and were also compared by one-way ANOVA. MAIN RESULTS: As results, we found a high variability of LPMC values among the models, a smaller variability of IP and UPMC values. We found a high percentage of unrecruited lung at LPMC, a small percentage of unrecruited lung at IP and no unrecruited lung at UPMC. SIGNIFICANCE: Our results confirm the notion of ongoing lung recruitment at pressure levels above LPMC for all investigated model equations and highlight the importance of a regional assessment of lung recruitment in patients with ARDS.

[Health-related quality of life after mechanical ventilation in the intensive care unit]. / Gesundheitsbezogene Lebensqualität nach Beatmung auf der Intensivstation.

BACKGROUND: It is unknown whether health related quality of life measured in German patients one year after mechanical ventilation in the intensive care unit is impaired or not. OBJECTIVES: The aim of this study was to assess health related quality of life one year after inclusion into a randomized controlled trial for weaning from mechanical ventilation with the help of a questionnaire that has never been used in critically ill patients and to investigate whether health related quality of life scores differ between the study population and a general German population. METHODS: We followed up with patients one year after inclusion into a randomized control trial investigating the effect of SmartCare/PS on total ventilation time compared to protocol-driven weaning (ASOPI trial, clinicaltrials.gov ID00445289). Health related quality of life was measured using the quality of life questionnaire C­30 version 3.0 from the European Organization of Research and Treatment of Cancer (EORTC). Mean differences of at least 10 score points in the quality of life scales were considered clinically significant. RESULTS: Of the 232 patients who were alive 90 days after study inclusion, 24 patients died one year after study inclusion and 64 patients were lost to follow-up. Of the remaining145 patients who were successfully contacted, 126 patients agreed to fill out the questionnaire. Questionnaires were sent back to the study site by 83 patients and these were analyzed. Health-related quality of life was significantly lower in five of the six functional scales (physical functioning, role functioning, cognitive functioning, social functioning, global health status) and in eight of the nine symptom scales (fatigue, pain, dyspnea, insomnia, appetite loss, constipation, diarrhea, financial difficulties) compared to the reference values of a German normal population. CONCLUSIONS: The EORTC QLQ-C30 questionnaire is suitable for the acquisition of the health-related quality of life in formerly critically ill patients. Health-related quality of life is severely impaired after mechanical ventilation in the intensive care unit. Future studies should consider health related quality of life as a possible study endpoint.

A collaborative EDNAP exercise on SNaPshot™-based mtDNA control region typing.

A collaborative European DNA Profiling (EDNAP) Group exercise was undertaken to assess the performance of an earlier described SNaPshot™-based screening assay (denoted mini-mtSNaPshot) (Weiler et al., 2016) [1] that targets 18 single nucleotide polymorphism (SNP) positions in the mitochondrial (mt) DNA control region and allows for discrimination of major European mtDNA haplogroups. Besides the organising laboratory, 14 forensic genetics laboratories were involved in the analysis of 13 samples, which were centrally prepared and thoroughly tested prior to shipment. The samples had a variable complexity and comprised straightforward single-source samples, samples with dropout or altered peak sizing, a point heteroplasmy and two-component mixtures resulting in one to five bi-allelic calls. The overall success rate in obtaining useful results was high (97.6%) given that some of the participating laboratories had no previous experience with the typing technology and/or mtDNA analysis. The majority of the participants proceeded to haplotype inference to assess the feasibility of assigning a haplogroup and checking phylogenetic consistency when only 18 SNPs are typed. To mimic casework procedures, the participants compared the SNP typing data of all 13 samples to a set of eight mtDNA reference profiles that were described according to standard nomenclature (Parson et al., 2014) [2], and indicated whether these references matched each sample or not. Incorrect scorings were obtained for 2% of the comparisons and derived from a subset of the participants, indicating a need for training and guidelines regarding mini-mtSNaPshot data interpretation.

The efficacy and safety of direct acting antiviral treatment and clinical significance of drug-drug interactions in elderly patients with chronic hepatitis C virus infection.

BACKGROUND: Direct antiviral therapies for chronic hepatitis C virus (HCV) infection have expanded treatment options for neglected patient populations, including elderly patients who are ineligible/intolerant to receive interferon (IFN)-based therapy. AIM: To investigate the efficacy, tolerability and potential for drug-drug interactions (DDIs) of IFN-free treatment in patients aged ≥65 years in a large real-world cohort. METHODS: A total of 541 patients were treated with different combinations of direct antiviral agents (DAAs: ledipasvir/sofosbuvir ±ribavirin; daclatasvir/sofosbuvir ±ribavirin; paritaprevir/ombitasvir ±dasabuvir ±ribavirin or simeprevir/sofosbuvir ±ribavirin in genotype 1/4, and daclatasvir/sofosbuvir ±ribavirin or sofosbuvir/ribavirin in genotype 2/3). Efficacy, safety and potential DDIs were analysed and compared between patients aged <65 years (n = 404) and patients aged ≥65 years (n = 137) of whom 41 patients were ≥75 years. RESULTS: Sustained virological response rates were 98% and 91% in patients aged ≥65 years and <65 years, respectively. Elderly patients took significantly more concomitant medications (79% vs. 51%; P < 0.0001). The number of concomitant drugs per patient was highest in patients ≥65 years with cirrhosis (median, three per patient; range, 0-10). Based on the hep-druginteractions database, the proportion of predicted clinically significant DDIs was significantly higher in elderly patients (54% vs. 28%; P < 0.0001). The number of patients who experienced treatment-associated adverse events was similar between the two age groups (63% vs. 65%; P = n.s.). CONCLUSIONS: Elderly patients are at increased risk for significant DDIs when treated with DAAs for chronic HCV infection. However, with careful pre-treatment assessment of concomitant medications, on-treatment monitoring or dose-modifications, significant DDIs and associated adverse events can be avoided.

Influence of torso and arm positions on chest examinations by electrical impedance tomography.

Electrical impedance tomography (EIT) is increasingly used in patients suffering from respiratory disorders during pulmonary function testing (PFT). The EIT chest examinations often take place simultaneously to conventional PFT during which the patients involuntarily move in order to facilitate their breathing. Since the influence of torso and arm movements on EIT chest examinations is unknown, we studied this effect in 13 healthy subjects (37 ± 4 years, mean age ± SD) and 15 patients with obstructive lung diseases (72 ± 8 years) during stable tidal breathing. We carried out the examinations in an upright sitting position with both arms adducted, in a leaning forward position and in an upright sitting position with consecutive right and left arm elevations. We analysed the differences in EIT-derived regional end-expiratory impedance values, tidal impedance variations and their spatial distributions during all successive study phases. Both the torso and the arm movements had a highly significant influence on the end-expiratory impedance values in the healthy subjects (p = 0.0054 and p < 0.0001, respectively) and the patients (p < 0.0001 in both cases). The global tidal impedance variation was affected by the torso, but not the arm movements in both study groups (p = 0.0447 and p = 0.0418, respectively). The spatial heterogeneity of the tidal ventilation distribution was slightly influenced by the alteration of the torso position only in the patients (p = 0.0391). The arm movements did not impact the ventilation distribution in either study group. In summary, the forward torso movement and the arms' abduction exert significant effects on the EIT waveforms during tidal breathing. We recommend strict adherence to the upright sitting position during PFT when EIT is used.

Regional lung function determined by electrical impedance tomography during bronchodilator reversibility testing in patients with asthma.

The measurement of rapid regional lung volume changes by electrical impedance tomography (EIT) could determine regional lung function in patients with obstructive lung diseases during pulmonary function testing (PFT). EIT examinations carried out before and after bronchodilator reversibility testing could detect the presence of spatial and temporal ventilation heterogeneities and analyse their changes in response to inhaled bronchodilator on the regional level. We examined seven patients suffering from chronic asthma (49 ± 19 years, mean age ± SD) using EIT at a scan rate of 33 images s(-1) during tidal breathing and PFT with forced full expiration. The patients were studied before and 5, 10 and 20 min after bronchodilator inhalation. Seven age- and sex-matched human subjects with no lung disease history served as a control study group. The spatial heterogeneity of lung function measures was quantified by the global inhomogeneity indices calculated from the pixel values of tidal volume, forced expiratory volume in one second (FEV1), forced vital capacity (FVC), peak flow and forced expiratory flow between 25% and 75% of FVC as well as histograms of pixel FEV1/FVC values. Temporal heterogeneity was assessed using the pixel values of expiration times needed to exhale 75% and 90% of pixel FVC. Regional lung function was more homogeneous in the healthy subjects than in the patients with asthma. Spatial and temporal ventilation distribution improved in the patients with asthma after the bronchodilator administration as evidenced mainly by the histograms of pixel FEV1/FVC values and pixel expiration times. The examination of regional lung function using EIT enables the assessment of spatial and temporal heterogeneity of ventilation distribution during bronchodilator reversibility testing. EIT may become a new tool in PFT, allowing the estimation of the natural disease progression and therapy effects on the regional and not only global level.

Influence of tidal volume on ventilation inhomogeneity assessed by electrical impedance tomography during controlled mechanical ventilation.

The global inhomogeneity (GI) index is a parameter of ventilation inhomogeneity that can be calculated from images of tidal ventilation distribution obtained by electrical impedance tomography (EIT). It has been suggested that the GI index may be useful for individual adjustment of positive end-expiratory pressure (PEEP) and for guidance of ventilator therapy. The aim of the present work was to assess the influence of tidal volume (VT) on the GI index values. EIT data from 9 patients with acute respiratory distress syndrome ventilated with a low and a high VT of 5 ± 1 (mean ± SD) and 9 ± 1 ml kg(-1) predicted body weight at a high and a low level of PEEP (PEEPhigh, PEEPlow) were analyzed. PEEPhigh and PEEPlow were set 2 cmH2O above and 5 cmH2O below the lower inflection point of a quasi-static pressure volume loop, respectively. The lower inflection point was identified at 8.1 ± 1.4 (mean ± SD) cmH2O, resulting in a PEEPhigh of 10.1 ± 1.4 and a PEEPlow of 3.1 ± 1.4 cmH2O. At PEEPhigh, we found no significant trend in GI index with low VT when compared to high VT (0.49 ± 0.15 versus 0.44 ± 0.09, p = 0.13). At PEEPlow, we found a significantly higher GI index with low VT compared to high VT (0.66 ± 0.19 versus 0.59 ± 0.17, p = 0.01). When comparing the PEEP levels, we found a significantly lower GI index at PEEPhigh both for high and low VT. We conclude that high VT may lead to a lower GI index, especially at low PEEP settings. This should be taken into account when using the GI index for individual adjustment of ventilator settings.

The wingless-related integration site-5a/secreted frizzled-related protein-5 system is dysregulated in human sepsis.

Sepsis and type 2 diabetes exhibit insulin resistance as a common phenotype. In type 2 diabetes we and others have recently provided evidence that alterations of the proinflammatory wingless-related integration site (wnt)-5a/anti-inflammatory secreted frizzled-related protein (sFRP)-5 system are involved in the pathogenesis of insulin resistance. The aim of the present study was to investigate whether this novel cytokine system is dysregulated in human sepsis, which may indicate a potential mechanism linking inflammation to metabolism. In this single-centre prospective observational study, critically ill adult septic patients were examined and proinflammatory wnt5a and wnt5a inhibitor sFRP5 were measured in serum samples by enzyme-linked immunosorbent assay (ELISA) at admission to the intensive care unit (ICU) and 5 days later. Sixty sepsis patients were included, and 30 healthy individuals served as controls. Wnt5a levels were found to be increased significantly in septic patients compared to healthy controls (2·21 ± 0·33 versus 0·32 ± 0·03 ng/ml, P < 0·0001). In contrast, sFRP5 was not altered significantly in septic patients (19·72 ± 3·06 versus 17·48 ± 6·38 ng/ml, P = 0·07). On admission to the ICU, wnt5a levels exhibited a significant positive correlation with the leucocyte count (rs = 0·3797, P = 0·004). Interestingly, in patients recovering from sepsis, wnt5a levels declined significantly within 5 days (2·17 ± 0·38-1·03 ± 0·28 ng/ml, P < 0·01). In contrast, if sepsis was worsening, wnt5a levels increased in the same time-period by trend (2·34 ± 0·59-3·25 ± 1·02 ng/ml, P > 0·05). sFRP5 levels did not change significantly throughout the study period. The wnt5a/sFRP5 system is altered in human sepsis and might therefore be of interest for future studies on molecular pathophysiology of this common human disease.