Identification of microRNA biomarkers simultaneously expressed in circulating extracellular vesicles and atherosclerotic plaques.

Background: Atherosclerosis is a widespread disorder of the cardiovascular system. The early detection of plaques by circulating biomarkers is highly clinically relevant to prevent the occurrence of major complications such as stroke or heart attacks. It is known that extracellular vesicles (EVs) are important in intercellular communication in atherosclerotic disorders and carry many components of their cells of origin, including microRNAs (miRNAs). In this study, we test the assumption that miRNAs present in material acquired from plaques in patients undergoing surgery for atherosclerotic carotid artery stenosis are also expressed in circulating EVs obtained from the identical patients. This would allow the adoption of a liquid biopsy approach for the detection of plaques. Methods: We studied 22 surgical patients with atherosclerotic carotid arterial stenosis and 28 healthy controls. EVs were isolated from serum by precipitation. miRNA expression profiles of serum-derived EVs were obtained by small RNA sequencing and in plaque material simultaneously acquired from patients. A comparative analysis was performed to identify circulating atherosclerosis-associated miRNAs that are also detectable in plaques. Results: Seven miRNAs were found to be differentially regulated in patient serum compared with the serum of healthy controls. Of these, miR-193b-5p, miR-193a-5p, and miR-125a-3p were significantly upregulated in patients compared with that in healthy controls and present in both, circulating EVs and plaque material. An overrepresentation analysis of experimentally validated mRNA targets revealed an increased regulation of inflammation and vascular growth factors, key players in atherosclerosis and plaque formation. Conclusion: Our findings suggest that circulating EVs reflect plaque development in patients with symptomatic carotid artery stenosis, which can serve as biomarker candidates for detecting the presence of atherosclerotic plaques.

Do higher alarm thresholds for arterial blood pressure lead to less perioperative hypotension? A retrospective, observational cohort study.

Arterial blood pressure is one of the vital signs monitored mandatory in anaesthetised patients. Even short episodes of intraoperative hypotension are associated with increased risk for postoperative organ dysfunction such as acute kidney injury and myocardial injury. Since there is little evidence whether higher alarm thresholds in patient monitors can help prevent intraoperative hypotension, we analysed the blood pressure data before (group 1) and after (group 2) the implementation of altered hypotension alarm settings. The study was conducted as a retrospective observational cohort study in a large surgical centre with 32 operating theatres. Alarm thresholds for hypotension alarm for mean arterial pressure (MAP) were altered from 60 (before) to 65 mmHg for invasive measurement and 70 mmHg for noninvasive measurement. Blood pressure data from electronic anaesthesia records of 4222 patients (1982 and 2240 in group 1 and 2, respectively) with 406,623 blood pressure values undergoing noncardiac surgery were included. We analysed (A) the proportion of blood pressure measurements below the threshold among all measurements by quasi-binomial regression and (B) whether at least one blood pressure measurement below the threshold occurred by logistic regression. Hypotension was defined as MAP < 65 mmHg. There was no significant difference in overall proportions of hypotensive episodes for mean arterial pressure before and after the adjustment of alarm settings (mean proportion of values below 65 mmHg were 6.05% in group 1 and 5.99% in group 2). The risk of ever experiencing a hypotensive episode during anaesthesia was significantly lower in group 2 with an odds ratio of 0.84 (p = 0.029). In conclusion, higher alarm thresholds do not generally lead to less hypotensive episodes perioperatively. There was a slight but significant reduction of the occurrence of intraoperative hypotension in the presence of higher thresholds for blood pressure alarms. However, this reduction only seems to be present in patients with very few hypotensive episodes.

Oscillometric versus invasive blood pressure measurement in patients with shock: a prospective observational study in the emergency department.

In emergency medicine, blood pressure is often measured by an oscillometric device using an upper arm cuff. However, measurement accuracy of this technique in patients suffering from hypotensive shock has not been sufficiently evaluated. We designed a prospective observational study investigating the accuracy of an oscillometric device in hypotensive patients admitted to the resuscitation area of the emergency department. Patients admitted to the resuscitation area of a university hospital, who were equipped with an arterial catheter and found to be hypotensive (mean arterial pressure (MAP) < 60 mmHg) were eligible for the study. Blood pressure was measured simultaneously via upper arm cuff and invasively under routine clinical conditions. After data extraction, Bland-Altman analysis, correlation coefficient and percentage error of mean and systolic blood pressure pairs were performed. We analysed 75 simultaneously obtained blood pressure measurements of 30 patients in hypotension, 11 (37%) were female, median age was 76.5 years (IQR 63-82). Oscillometric MAP was markedly higher than invasive MAP with a mean of the differences of 13 ± 15 mmHg (oscillometric-invasive), 95% limits of agreement - 16 to 41 mmHg, percentage error was 76%. In 64% of readings, values obtained by the upper arm cuff were not able to detect hypotension. Oscillometric blood pressure measurement is not able to reliably detect hypotension in emergency patients. Therefore, direct measurement of blood pressure should be established as soon as possible in patients suffering from shock.

Exhaled Breath and Oxygenator Sweep Gas Propionaldehyde in Acute Respiratory Distress Syndrome.

BACKGROUND: Oxidative stress-induced lipid peroxidation (LPO) due to neutrophil-derived reactive oxygen species plays a key role in the early stage of the acute respiratory distress syndrome (ARDS). Monitoring of oxidative stress in this patient population is of great interest, and, ideally, this can be done noninvasively. Recently, propionaldehyde, a volatile chemical compound (VOC) released during LPO, was identified in the breath of lung transplant recipients as a marker of oxidative stress. The aim of the present study was to identify if markers of oxidative stress appear in the oxygenator outflow gas of patients with severe ARDS treated with veno-venous extracorporeal membrane oxygenation (ECMO). METHODS: The present study included patients with severe ARDS treated with veno-venous ECMO. Concentrations of acetone, isoprene, and propionaldehyde were measured in inspiratory air, exhaled breath, and oxygenator inflow and outflow gas at corresponding time points. Ion-molecule reaction mass spectrometry was used to measure VOCs in a sequential order within the first 24 h and on day three after ECMO initiation. RESULTS: Nine patients (5 female, 4 male; age = 42.1 ± 12.2 year) with ARDS and already established ECMO therapy (pre-ECMO PaO2/FiO2 = 44.0 ± 11.5 mmHg) were included into analysis. VOCs appeared in comparable amounts in breath and oxygenator outflow gas (acetone: 838 (422-7632) vs. 1114 (501-4916) ppbv; isoprene: 53.7 (19.5-244) vs. 48.7 (37.9-108) ppbv; propionaldehyde: 53.7 (32.1-82.2) vs. 42.9 (24.8-122) ppbv). Concentrations of acetone, isoprene, and propionaldehyde in breath and oxygenator outflow gas showed a parallel course with time. CONCLUSIONS: Acetone, isoprene, and propionaldehyde appear in breath and oxygenator outflow gas in comparable amounts. This allows for the measurement of these VOCs in a critically ill patient population via the ECMO oxygenator outflow gas without the need of ventilator circuit manipulation.

Improve hip fracture outcome in the elderly patient (iHOPE): a study protocol for a pragmatic, multicentre randomised controlled trial to test the efficacy of spinal versus general anaesthesia.

INTRODUCTION: Hip fracture surgery is associated with high in-hospital and 30-day mortality rates and serious adverse patient outcomes. Evidence from randomised controlled trials regarding effectiveness of spinal versus general anaesthesia on patient-centred outcomes after hip fracture surgery is sparse. METHODS AND ANALYSIS: The iHOPE study is a pragmatic national, multicentre, randomised controlled, open-label clinical trial with a two-arm parallel group design. In total, 1032 patients with hip fracture (>65 years) will be randomised in an intended 1:1 allocation ratio to receive spinal anaesthesia (n=516) or general anaesthesia (n=516). Outcome assessment will occur in a blinded manner after hospital discharge and inhospital. The primary endpoint will be assessed by telephone interview and comprises the time to the first occurring event of the binary composite outcome of all-cause mortality or new-onset serious cardiac and pulmonary complications within 30 postoperative days. In-hospital secondary endpoints, assessed via in-person interviews and medical record review, include mortality, perioperative adverse events, delirium, satisfaction, walking independently, length of hospital stay and discharge destination. Telephone interviews will be performed for long-term endpoints (all-cause mortality, independence in walking, chronic pain, ability to return home cognitive function and overall health and disability) at postoperative day 30±3, 180±45 and 365±60. ETHICS AND DISSEMINATION: iHOPE has been approved by the leading Ethics Committee of the Medical Faculty of the RWTH Aachen University on 14 March 2018 (EK 022/18). Approval from all other involved local Ethical Committees was subsequently requested and obtained. Study started in April 2018 with a total recruitment period of 24 months. iHOPE will be disseminated via presentations at national and international scientific meetings or conferences and publication in peer-reviewed international scientific journals. TRIAL REGISTRATION NUMBER: DRKS00013644; Pre-results.

Exhaled breath volatile organic and inorganic compound composition in end-stage renal disease.

AIMS: Patients with end-stage renal disease (ESRD) are characterized by uremia and increased oxidative stress. The aim of this study was to investigate the influence of hemodialysis on breath ammonia and volatile oxidative stress parameters. METHODS: Breath analysis was performed in 18 ESRD patients prior, during, and 30 minutes after a hemodialysis session. Parameters of hemodialysis efficiency and oxidative stress (lipid peroxides, total antioxidative capacity, myeloperoxidase, and malondialdehyde) were measured in blood at the beginning, after 30 minutes, and at the end of the dialysis session. 11 healthy volunteers with normal renal function served as a control group. Ion-molecule reaction mass spectrometry was used for breath-gas analysis. RESULTS: Initial elevated concentrations of breath ammonia decreased during hemodialysis and correlated with serum urea levels (r2 = 0.74), whereas isoprene concentrations increased. Breath concentrations of malondialdehyde and pentane (MDA-P) were significantly elevated in ESRD patients (p < 0.01). Within the blood, a significant decrease of malondialdehyde was notable during hemodialysis treatment, whereas levels of lipid peroxides and myeloperoxidase increased. CONCLUSION: Exhaled breath of patients with ESRD on regular hemodialysis treatment is characterized by an increase in ammonia and MDA-P. The efficient decrease of breath ammonia and its close correlation to serum urea during hemodialysis suggests its possible use as a noninvasive marker to monitor dialysis efficacy.

Gram-negative and -positive bacteria differentiation in blood culture samples by headspace volatile compound analysis.

BACKGROUND: Identification of microorganisms in positive blood cultures still relies on standard techniques such as Gram staining followed by culturing with definite microorganism identification. Alternatively, matrix-assisted laser desorption/ionization time-of-flight mass spectrometry or the analysis of headspace volatile compound (VC) composition produced by cultures can help to differentiate between microorganisms under experimental conditions. This study assessed the efficacy of volatile compound based microorganism differentiation into Gram-negatives and -positives in unselected positive blood culture samples from patients. METHODS: Headspace gas samples of positive blood culture samples were transferred to sterilized, sealed, and evacuated 20 ml glass vials and stored at -30 °C until batch analysis. Headspace gas VC content analysis was carried out via an auto sampler connected to an ion-molecule reaction mass spectrometer (IMR-MS). Measurements covered a mass range from 16 to 135 u including CO2, H2, N2, and O2. Prediction rules for microorganism identification based on VC composition were derived using a training data set and evaluated using a validation data set within a random split validation procedure. RESULTS: One-hundred-fifty-two aerobic samples growing 27 Gram-negatives, 106 Gram-positives, and 19 fungi and 130 anaerobic samples growing 37 Gram-negatives, 91 Gram-positives, and two fungi were analysed. In anaerobic samples, ten discriminators were identified by the random forest method allowing for bacteria differentiation into Gram-negative and -positive (error rate: 16.7 % in validation data set). For aerobic samples the error rate was not better than random. CONCLUSIONS: In anaerobic blood culture samples of patients IMR-MS based headspace VC composition analysis facilitates bacteria differentiation into Gram-negative and -positive.

Influence of abdominal obesity on multiorgan dysfunction and mortality in acute respiratory distress syndrome patients treated with prone positioning.

PURPOSE: Obesity is a worldwide pandemic, and obese patients face an increased risk of developing acute respiratory distress syndrome (ARDS). Prone positioning (PP) is a frequently used intervention in the treatment of ARDS. There are no data describing the impact of PP on morbidity and mortality in abdominally obese patients. We report our observations in abdominally obese ARDS patients treated with PP. MATERIALS AND METHODS: Patients with ARDS (n=82) were retrospectively divided into 2 groups characterized by presence (n=41) or absence (n=41) of abdominal obesity as defined by a sagittal abdominal diameter of 26 cm or more. RESULTS: There was no difference in cumulative time abdominally obese patients were placed in prone position from admission to day 7 (41.0 hours [interquartile range, 50.5 hours] vs 39.5 hours [interquartile range, 61.5 hours]; P=.65) or in overall intensive care unit mortality (34% vs 34%; P=1). However, abdominally obese patients developed renal failure (83% vs 35%; P<.001) and hypoxic hepatitis (22% vs 2%; P=.015) more frequently. A significant interaction effect between abdominal obesity and prone position with respect to mortality risk (likelihood ratio, P=.0004) was seen if abdominally obese patients were treated with prolonged cumulative PP. CONCLUSION: A cautious approach to PP should be considered in abdominally obese patients.

Munich lung transplant group: waiting list during the first 9 months of the lung allocation score era.

OBJECTIVE AND METHODS: The Eurotransplant Foundation introduced the lung allocation score (LAS) in Germany on December 10, 2011. We analyzed characteristics of the Munich Lung Transplant Group (MLTG) waiting list during the first 9 months after the introduction of the LAS. RESULTS: A mean number of 39 ± 1 patients were constantly listed for lung transplantation and 60 transplants were performed by the MLTG during the observation period. While the majority (42 ± 0%) of patients waiting for transplant comprised chronic obstructive pulmonary disease (COPD)/emphysema patients, only 26% of transplanted patients suffered from COPD/emphysema. Instead, the majority (42%) of transplanted patients suffered from interstitial lung disease. Waiting times did not markedly change in the LAS era. Notably, patients with interstitial lung disease had shorter waiting times when compared with patients suffering from COPD/emphysema and cystic fibrosis, both on the waiting list and at the time of transplant. CONCLUSION: The MLTG lung transplant waiting list has not markedly changed during the first 9 months after the introduction of the LAS. Our data indicate that the LAS accommodates disease-specific patient statuses well. Although patients with interstitial lung disease are preferably transplanted, the LAS system provides a very reasonable basis to also list and transplant COPD/emphysema patients.

Parameters associated with short- and midterm survival in bridging to lung transplantation with extracorporeal membrane oxygenation.

Patients with terminal lung failure may be bridged to lung transplantation (LTX) by extracorporeal membrane oxygenation (ECMO). With the present shortage of donor organs and the high level of invasiveness of ECMO treatment, appropriate selection criteria for bridge to transplant need to be defined. We report retrospective data from 26 patients on ECMO listed for LTX. Seven patients were successfully transplanted (LTX-s). Six patients survived until transplantation, but died intra- or post-operatively (LTX-ns). Thirteen patients died before transplantation (Fail). There was no difference between LTX-s and the 19 overall non-survivors (NS) prior to ECMO initiation with regard to demographic data or ventilator parameters except for higher PaO2 /FiO2 in the LTX-s. Time on ECMO pre-LTX did not differ in the LTX-s and LTX-ns groups. SOFA score was lower in LTX-s when compared to LTX-ns before ECMO (p = 0.0155), during bridging (p = 0.028), and right before transplantation (p = 0.0038). Maximal bilirubin during bridging and bilirubin prior to transplantation was markedly elevated in the LTX-ns group [4.2 (2.4-4.7) vs. 1.1 (0.8-2.0) mg/dL; p = 0.0266 and 1.6 (1.2-3.0) vs. 0.5 (0.5-0.5) mg/dL; p = 0.0047). Bridging to LTX is a challenging but viable option for selected patients. Special consideration should be given to hepatic function.

Determination of breath isoprene allows the identification of the expiratory fraction of the propofol breath signal during real-time propofol breath monitoring.

Real-time measurement of propofol in the breath may be used for routine clinical monitoring. However, this requires unequivocal identification of the expiratory phase of the respiratory propofol signal as only expiratory propofol reflects propofol blood concentrations. Determination of CO2 breath concentrations is the current gold standard for the identification of expiratory gas but usually requires additional equipment. Human breath also contains isoprene, a volatile organic compound with low inspiratory breath concentration and an expiratory concentration plateau. We investigated whether breath isoprene could be used similarly to CO2 to identify the expiratory fraction of the propofol breath signal. We investigated real-time breath data obtained from 40 study subjects during routine anesthesia. Propofol, isoprene, and CO2 breath concentrations were determined by a combined ion molecule reaction/electron impact mass spectrometry system. The expiratory propofol signal was identified according to breath CO2 and isoprene concentrations and presented as median of intervals of 30 s duration. Bland-Altman analysis was applied to detect differences (bias) in the expiratory propofol signal extracted by the two identification methods. We investigated propofol signals in a total of 3,590 observation intervals of 30 s duration in the 40 study subjects. In 51.4 % of the intervals (1,844/3,590) both methods extracted the same results for expiratory propofol signal. Overall bias between the two data extraction methods was -0.12 ppb. The lower and the upper limits of the 95 % CI were -0.69 and 0.45 ppb. Determination of isoprene breath concentrations allows the identification of the expiratory propofol signal during real-time breath monitoring.

Abdominal obesity and prolonged prone positioning increase risk of developing sclerosing cholangitis in critically ill patients with influenza A-associated ARDS.

BACKGROUND: Secondary sclerosing cholangitis is a severe disease of the biliary tract. Over the last decade, several cases of sclerosing cholangitis in critically ill patients (SC-CIP) were reported. Reports in the literature so far are characterized by a wide variety of underlying causes of critical illness, thereby hindering a risk-factor analysis. We report on a homogenous cohort of critically ill patients with influenza A (H1N1) pneumonia and severe acute respiratory distress syndrome (ARDS), of whom a subgroup developed sclerosing cholangitis, allowing for probing of risk factors associated with SC-CIP. METHODS: Twenty-one patients (5 female, 16 male, 46.3 ± 10.8 years) with severe ARDS due to H1N1 pneumonia were retrospectively divided into two groups, characterized by the presence (n = 5) and absence of SC-CIP (n = 16). A large array of clinical data, laboratory parameters, and multi-detector computed tomography-derived measures were compared. RESULTS: Both patient groups showed severe pulmonary impairment. Severity of disease on admission day and during the first 14 days of treatment showed no difference. The patients developing SC-CIP had a higher body mass index (BMI) (37.4 ± 6.0 kg/m(2) vs. 29.3 ± 6.8 kg/m(2); P = 0.029) and a higher volume of intraperitoneal fat (8273 ± 3659 cm(3) vs. 5131 ± 2268 cm(3); P = 0.033) and spent a longer cumulative period in the prone position during the first 14 days (165 ± 117 h vs. 78 ± 61 h; P = 0.038). CONCLUSION: Our results suggest that obesity, intraperitoneal fat volume, and a longer cumulative duration spent in the prone position may put patients with ARDS at risk of developing SC-CIP. These results lead us to propose that the prone position should be carefully deployed, particularly in abdominally obese patients, and that frequent checks be made for early hepatic dysfunction.

Breath isoprene concentrations in persons undergoing general anesthesia and in healthy volunteers.

Human breath contains an abundance of volatile organic compounds (VOCs). Analysis of breath VOC may be used for diagnosis of various diseases or for on-line monitoring in anesthesia and intensive care. However, VOC concentrations largely depend on the breath sampling method and have a large inter-individual variability. For the development of breath tests, the influence of breath sampling methods and study subject characteristics on VOC concentrations has to be known. Therefore, we investigated the VOC isoprene in 62 study subjects during anesthesia and 16 spontaneously breathing healthy volunteers to determine (a) the influence of artificial and spontaneous ventilation and (b) the influence of study subject characteristics on breath isoprene concentrations. We used ion molecule reaction mass spectrometry for high-resolution breath-by-breath analysis of isoprene. We found that persons during anesthesia had significantly increased inspiratory and end-expiratory isoprene breath concentrations. Measured isoprene concentrations (median [first quartile-third quartile]) were in the anesthesia group: 54 [40-79] ppb (inspiratory) and 224 [171-309] ppb (end-expiratory), volunteer group: 14 [11-17] ppb (inspiratory) and 174 [124-202] ppb (end-expiratory). Higher end-tidal CO(2) concentrations in ventilated subjects were associated with higher expiratory isoprene levels. Furthermore, inspiratory and end-expiratory isoprene concentrations were correlated during anesthesia (r = 0.603, p < 0.001). Multivariate analysis showed that men had significantly higher end-expiratory isoprene concentrations than women. Rebreathing of isoprene from the anesthesia machine possibly accounts for the observed increase in isoprene in the anesthesia group.

Arterial chimney graft cannulation for interventional lung assist.

An interventional lung assist membrane ventilator (iLA) for arteriovenous extracorporeal CO2 removal was connected to a small-diameter femoral artery by use of a chimney graft in an underweight patient with acute respiratory failure and a previous history of heart-lung transplantation. This concept offers additional therapeutic options in underweight patients requiring extracorporeal CO2 removal with arterial vessels that are too small for percutaneous arterial cannulation with standard-sized percutaneous insertable iLA cannulae.

Time course of expiratory propofol after bolus injection as measured by ion molecule reaction mass spectrometry.

Propofol in exhaled breath can be detected and monitored in real time by ion molecule reaction mass spectrometry (IMR-MS). In addition, propofol concentration in exhaled breath is tightly correlated with propofol concentration in plasma. Therefore, real-time monitoring of expiratory propofol could be useful for titrating intravenous anesthesia, but only if concentration changes in plasma can be determined in exhaled breath without significant delay. To evaluate the utility of IMR-MS during non-steady-state conditions, we measured the time course of both expiratory propofol concentration and the processed electroencephalography (EEG) as a surrogate outcome for propofol effect after an IV bolus induction of propofol. Twenty-one patients scheduled for routine surgery were observed after a bolus of 2.5 mg kg(-1) propofol for induction of anesthesia. Expiratory propofol was measured using IMR-MS and the cerebral propofol effect was estimated using the bispectral index (BIS). Primary endpoints were time to detection of expiratory propofol and time to onset of propofol's effect on BIS, and the secondary endpoint was time to peak effect (highest expiratory propofol or lowest BIS). Expiratory propofol and changes in BIS were first detected at 43 ± 21 and 49 ± 11 s after bolus injection, respectively (P = 0.29). Peak propofol concentrations (9.2 ± 2.4 parts-per-billion) and lowest BIS values (23 ± 4) were reached after 208 ± 57 and 219 ± 62 s, respectively (P = 0.57). Expiratory propofol concentrations measured by IMR-MS have similar times to detection and peak concentrations compared with propofol effect as measured by the processed EEG (BIS). This suggests that expiratory propofol concentrations may be useful for titrating intravenous anesthesia.

Delayed intracardial shunting and hypoxemia after massive pulmonary embolism in a patient with a biventricular assist device.

We describe the interdisciplinary management of a 34-year-old woman with dilated cardiomyopathy three months postpartum on a cardiac biventricular assist device (BVAD) as bridge to heart transplantation with delayed onset of intracardial shunting and subsequent hypoxemia due to massive pulmonary embolism. After emergency surgical embolectomy pulmonary function was highly compromised (PaO2/FiO2 54) requiring bifemoral veno-venous extracorporeal membrane oxygenation. Transesophageal echocardiography detected atrial level hypoxemic right-to-left shunting through a patent foramen ovale (PFO). Percutaneous closure of the PFO was achieved with a PFO occluder device. After placing the PFO occluder device oxygenation increased significantly (Δ paO2 119 Torr). The patient received heart transplantation 20 weeks after BVAD implantation and was discharged from ICU 3 weeks after transplantation.An increase in pulmonary vascular resistance in patients on BVAD can reopen a PFO resulting in atrial right-to-left shunting and subsequent hypoxemia. The case demonstrates the usefulness of transesophageal echocardiography examinations in the detection of this unexpected event. Percutaneous placement of a PFO occluder device is an appropriate strategy to stop intracardiac shunting through PFO in fixed elevation of pulmonary vascular resistance.

Transesophageal echocardiography-guided technique for extracorporeal membrane oxygenation dual-lumen catheter placement.

In acute respiratory distress syndrome (ARDS) with severe hypoxemia or respiratory acidosis, veno-venous extracorporeal membrane oxygenation (VV-ECMO) ensures oxygenation and decarboxylation. Commonly, simultaneous cannulation of jugular and femoral veins is used for VV-ECMO. A recently introduced dual-lumen cannula for VV-ECMO promises single vessel access through the right internal jugular vein and patient ambulation. However, correct direction of the reinfusion jet toward the tricuspid valve during ECMO treatment requires more demanding cannula placement control. We present a new ultrasound-guided technique for the placement of a dual-lumen VV-ECMO cannula in a patient with ARDS and extreme obesity.

Extracorporeal membrane oxygenation bridging to lung transplant complicated by heparin-induced thrombocytopenia.

In patients with acute respiratory failure and life-threatening impairment of pulmonary gas exchange, venovenous extracorporeal membrane oxygenation offers further therapeutic options. During extracorporeal membrane oxygenation treatment, systemic anticoagulation is usually achieved by heparin administration, which exposes patients to the risk of heparin-induced thrombocytopenia type II. We present a patient with acute respiratory distress syndrome on venovenous extracorporeal membrane oxygenation who experienced heparin-induced thrombocytopenia type II and in whom anticoagulation was continued with argatroban. Because respiratory failure did not resolve, the patient was bridged to lung transplant with extracorporeal membrane oxygenation. Argatroban anticoagulation was safely used until lung transplant (on day 114 after extracorporeal membrane oxygenation initiation) and after transplant in the presence of hepatic failure.

Fulminant primary manifestations of Wegener's granulomatosis might not be pauci-immune.

Wegener's granulomatosis is an ANCA-associated small vessel vasculitis. Because histologically immune complex deposits are frequently lacking, the term pauci-immune has been introduced for this subgroup. We report a patient with fulminant, severe PR3-ANCA-positive Wegener's granulomatosis and multi-organ involvement (upper respiratory tract, lung, kidneys, skin and general symptoms), who showed pronounced immunoglobulin and complement deposits within the skin biopsy. Our observation supports the hypothesis that immune complex deposits may be under-recognized in early lesions of ANCA-associated Wegener's granulomatosis.