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Enjoyment is recognized as a determinant of physical activity habits. The enjoyment of engaging in physical activity can be measured with the Physical Activity Enjoyment Scale (PACES). Later versions of this scale have been shortened to capture the component of subjective feeling, which has been validated using German-speaking samples. The aim of this study was to examine internal consistency, factorial validity, criterion-related validity, test-retest reliability, and measurement invariance (across gender and languages) in an English-speaking population. Data on physical activity enjoyment and self-reported physical activity were collected through an online survey with a test-retest design (n = 276,189 female, M = 42.55, SD = 16.81 years) conducted from September 2023 to December 2023. In addition, a German-speaking sample (n = 1017, 497 female, M = 29.77, SD = 13.54 years) was analyzed to assess measurement invariance with respect to language. McDonald's omega at time 1 was ω = 0.95. The confirmatory factor analysis supports the assumption of the unidimensional structure of PACES-S (χ2 = 19.8, df = 2, p < 0.05; CFI = 0.984; RMSEA = 0.180, 90% CI [0.113-0.256]), as the model fit can be estimated as good in view of the CFI value, while the sensitivity of the χ2 test is very high and the RMSEA may underestimate the model fit. Although the RMSEA value is higher than the conventional threshold, the small number of degrees of freedom may have a significant impact on this indicator. The criterion-related validity for light physical activity was r(107) = 0.26 (p < 0.05). The retest reliability was r(199) = 0.69 (p < 0.05). Further, the results supported measurement invariance across gender and partial measurement invariance across languages. Overall, the English PACES-S demonstrated good psychometric properties specifically for light intensity of physical activity, and can serve as an economical instrument to assess physical activity enjoyment., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Weyland et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Background: Healthcare simulation education often aims to promote transfer of learning: the application of knowledge, skills, and attitudes acquired during simulations to new situations in the workplace. Although achieving transfer is challenging, existing theories and models can provide guidance., Recommendations: This paper provides five general recommendations to design simulations that foster transfer: (1) emphasize whole-task practice, (2) consider a cognitive task analysis, (3) embed simulations within more comprehensive programs, (4) strategically combine and align simulation formats, and (5) optimize cognitive load. We illustrate the application of these five recommendations with a blueprint for an educational program focusing on simulation activities., Conclusions: More evidence-informed approaches to healthcare simulation might require a paradigm shift. We must accept that a limited number of simulations is not enough to develop complex skills. It requires comprehensive programs that combine simulation sessions with workplace learning., (© 2023. The Author(s).)

A new measure of the short form of the Physical Activity Enjoyment Scale (PACES-S), including four items, has been developed that focuses on the subjective experience of enjoyment. As validation has so far only been conducted in a youth population, the purpose of the present article was to test the psychometric properties of the measure in an adult population in three studies. In the first study ( n = 1017) the results supported the unidimensional structure of the instrument (χ 2 = 10.0; df = 2; p < 0.01; CFI = 0.992; RMSEA = 0.063), revealed a satisfactory level of internal consistency ( ω = 0.79), and showed that the measure is invariant across gender. The results on factorial validity and internal consistency were generally supported by the second study ( n = 482), which additionally showed satisfactory test-retest reliability ( r = 0.73). Finally, the third study ( n = 1336) also supported the factorial validity and internal consistency of the measure and additionally showed a positive correlation with physical activity ( r = 0.40), thus supporting the criterion-related validity of the measure. This more economical version of PACES seems to be particularly useful for large-scale studies.

The cerebral pressure reactivity index (PRx), through intracranial pressure (ICP) measurements, informs clinicians about the cerebral autoregulation (CA) status in adult-sedated patients with traumatic brain injury (TBI). Using PRx in clinical practice is currently limited by variability over shorter monitoring periods. We applied an innovative method to reduce the PRx variability by ventilator-induced slow (1/min) positive end-expiratory pressure (PEEP) oscillations. We hypothesized that, as seen in a previous animal model, the PRx variability would be reduced by inducing slow arterial blood pressure (ABP) and ICP oscillations without other clinically relevant physiological changes. Patients with TBI were ventilated with a static PEEP for 30 min (PRx period) followed by a 30-min period of slow [1/min (0.0167 Hz)] +5 cmH 2 O PEEP oscillations (induced ( i PRx period). Ten patients with TBI were included. No clinical monitoring was discontinued and no additional interventions were required during the i PRx period. The PRx variability [measured as the standard deviation (SD) of PRx] decreased significantly during the i PRx period from 0.25 (0.22-0.30) to 0.14 (0.09-0.17) ( P = 0.006). There was a power increase around the induced frequency (1/min) for both ABP and ICP ( P = 0.002). In conclusion, 1/min PEEP-induced oscillations reduced the PRx variability in patients with TBI with ICP levels <22 mmHg. No other clinically relevant physiological changes were observed. Reduced PRx variability might improve CA-guided perfusion management by reducing the time to find "optimal" perfusion pressure targets. Larger studies with prolonged periods of PEEP-induced oscillations are required to take it to routine use. NEW & NOTEWORTHY Cerebral autoregulation assessment requires sufficient slow arterial blood pressure (ABP) waves. However, spontaneous ABP waves may be insufficient for reliable cerebral autoregulation estimations. Therefore, we applied a ventilator "sigh-function" to generate positive end-expiratory pressure oscillations that induce slow ABP waves. This method demonstrated a reduced variability of the pressure reactivity index, commonly used as continuous cerebral autoregulation measure in a traumatic brain injury population.

Patients with SARS-CoV-2 infection present with different lung compliance and progression of disease differs. Measures of lung mechanics in SARS-CoV-2 patients may unravel different pathophysiologic mechanisms during mechanical ventilation. The objective of this prospective observational study is to describe whether Electrical Impedance Tomography (EIT) guided positive end-expiratory pressure (PEEP) levels unravel changes in EIT-derived parameters over time and whether the changes differ between survivors and non-survivors. Serial EIT-measurements of alveolar overdistension, collapse, and compliance change in ventilated SARS-CoV-2 patients were analysed. In 80 out of 94 patients, we took 283 EIT measurements (93 from day 1-3 after intubation, 66 from day 4-6, and 124 from day 7 and beyond). Fifty-one patients (64%) survived the ICU. At admission mean PaO 2 /FiO 2 -ratio was 184.3 (SD 61.4) vs. 151.3 (SD 54.4) mmHg, (p = 0.017) and PEEP was 11.8 (SD 2.8) cmH 2 O vs. 11.3 (SD 3.4) cmH 2 O, (p = 0.475), for ICU survivors and non-survivors. At day 1-3, compliance was ~ 55 mL/cmH 2 O vs. ~ 45 mL/cmH 2 O in survivors vs. non-survivors. The intersection of overdistension and collapse curves appeared similar at a PEEP of ~ 12-13 cmH 2 O. At day 4-6 compliance changed to ~ 50 mL/cmH 2 O vs. ~ 38 mL/cmH 2 O. At day 7 and beyond, compliance was ~ 38 mL/cmH 2 O with the intersection at a PEEP of ~ 9 cmH 2 O vs. ~ 25 mL/cmH 2 O with overdistension intersecting at collapse curves at a PEEP of ~ 7 cmH 2 O. Surviving SARS-CoV-2 patients show more favourable EIT-derived parameters and a higher compliance compared to non-survivors over time. This knowledge is valuable for discovering the different groups., (© 2022. The Author(s).)

Background: Electrical impedance tomography (EIT) visualises alveolar overdistension and alveolar collapse and enables optimisation of ventilator settings by using the best balance between alveolar overdistension and collapse (ODCL). Besides, the global inhomogeneity index (GI), measured by EIT, may also be of added value in determining PEEP. Optimal PEEP is often determined based on the best dynamic compliance without EIT at the bedside. This study aimed to assess the effect of a PEEP trial on ODCL, GI and dynamic compliance in patients with and without ARDS. Secondly, PEEP levels from "optimal PEEP" approaches by ODCL, GI and dynamic compliance are compared., Methods: In 2015-2016, we included patients with ARDS using postoperative cardiothoracic surgery patients as a reference group. A PEEP trial was performed with four consecutive incremental followed by four decremental PEEP steps of 2 cmH 2 O. Primary outcomes at each step were GI, ODCL and best dynamic compliance. In addition, the agreement between ODCL, GI, and dynamic compliance was determined for the individual patient., Results: Twenty-eight ARDS and 17 postoperative cardiothoracic surgery patients were included. The mean optimal PEEP, according to best compliance, was 10.3 (±2.9) cmH 2 O in ARDS compared to 9.8 (±2.5) cmH 2 O in cardiothoracic surgery patients. Optimal PEEP according to ODCL was 10.9 (±2.5) in ARDS and 9.6 (±1.6) in cardiothoracic surgery patients. Optimal PEEP according to GI was 17.1 (±3.9) in ARDS compared to 14.2 (±3.4) in cardiothoracic surgery patients., Conclusions: Currently, no golden standard to titrate PEEP is available. We showed that when using the GI, PEEP requirements are higher compared to ODCL and best dynamic compliance during a PEEP trial in patients with and without ARDS., (© 2022. The Author(s).)

Objectives: To investigate healthcare system-driven variation in general characteristics, interventions, and outcomes in coronavirus disease 2019 (COVID-19) patients admitted to the ICU within one Western European region across three countries., Design: Multicenter observational cohort study., Setting: Seven ICUs in the Euregio Meuse-Rhine, one region across Belgium, The Netherlands, and Germany., Patients: Consecutive COVID-19 patients supported in the ICU during the first pandemic wave., Interventions: None., Measurements and Main Results: Baseline demographic and clinical characteristics, laboratory values, and outcome data were retrieved after ethical approval and data-sharing agreements. Descriptive statistics were performed to investigate country-related practice variation. From March 2, 2020, to August 12, 2020, 551 patients were admitted. Mean age was 65.4 ± 11.2 years, and 29% were female. At admission, Acute Physiology and Chronic Health Evaluation II scores were 15.0 ± 5.5, 16.8 ± 5.5, and 15.8 ± 5.3 (p = 0.002), and Sequential Organ Failure Assessment scores were 4.4 ± 2.7, 7.4 ± 2.2, and 7.7 ± 3.2 (p < 0.001) in the Belgian, Dutch, and German parts of Euregio, respectively. The ICU mortality rate was 22%, 42%, and 44%, respectively (p < 0.001). Large differences were observed in the frequency of organ support, antimicrobial/inflammatory therapy application, and ICU capacity. Mixed-multivariable logistic regression analyses showed that differences in ICU mortality were independent of age, sex, disease severity, comorbidities, support strategies, therapies, and complications., Conclusions: COVID-19 patients admitted to ICUs within one region, the Euregio Meuse-Rhine, differed significantly in general characteristics, applied interventions, and outcomes despite presumed genetic and socioeconomic background, admission diagnosis, access to international literature, and data collection are similar. Variances in healthcare systems' organization, particularly ICU capacity and admission criteria, combined with a rapidly spreading pandemic might be important drivers for the observed differences. Heterogeneity between patient groups but also healthcare systems should be presumed to interfere with outcomes in coronavirus disease 2019., Competing Interests: The authors have disclosed that they do not have any potential conflicts of interest., (Copyright © 2022 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the Society of Critical Care Medicine and Wolters Kluwer Health, Inc.)

Objectives: Interhospital transports of critically ill patients are high-risk medical interventions. Well-established parameters to quantify the quality of transports are currently lacking. We aimed to develop and cross-validate a score for interhospital transports., Setting: An expert panel developed a score for interhospital transport by a Mobile Intensive Care Unit (MICU), the QUality of Interhospital Transportation in the Euregion Meuse-Rhine (QUIT-EMR) score. The QUIT-EMR score is an overall sum score that includes component scores of monitoring and intervention variables of the neurological (proxy for airway patency), respiratory and circulatory organ systems, ranging from -12 to +12. A score of 0 or higher defines an adequate transport. The QUIT-EMR score was tested to help to quantify the quality of transport., Participants: One hundred adult patients were randomly included and the transport charts were independently reviewed and classified as adequate or inadequate by four transport experts (ie, anaesthetists/intensivists)., Outcome Measures: Subsequently, the level of agreement between the QUIT-EMR score and expert classification was calculated using Gwet's AC 1 ., Results: From April 2012 to May 2014, a total of 100 MICU transports were studied. The median (IQR) QUIT-EMR score was 1 (0-2). Experts classified six transports as inadequate. The percentage agreement between the QUIT-EMR score and experts' classification for adequate/inadequate transport ranged from 84% to 92% (Gwet's AC 1 0.81-0.91). The interobserver agreement between experts was 87% to 94% (Gwet's AC 1 0.89-0.98)., Conclusion: The QUIT-EMR score is a novel validated tool to score MICU transportation adequacy in future studies contributing to quality control and improvement., Trial Registration Number: NTR 4937., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Introduction: The course of the disease in SARS-CoV-2 infection in mechanically ventilated patients is unknown. To unravel the clinical heterogeneity of the SARS-CoV-2 infection in these patients, we designed the prospective observational Maastricht Intensive Care COVID cohort (MaastrICCht). We incorporated serial measurements that harbour aetiological, diagnostic and predictive information. The study aims to investigate the heterogeneity of the natural course of critically ill patients with a SARS-CoV-2 infection., Methods and Analysis: Mechanically ventilated patients admitted to the intensive care with a SARS-CoV-2 infection will be included. We will collect clinical variables, vital parameters, laboratory variables, mechanical ventilator settings, chest electrical impedance tomography, ECGs, echocardiography as well as other imaging modalities to assess heterogeneity of the course of a SARS-CoV-2 infection in critically ill patients. The MaastrICCht is also designed to foster various other studies and registries and intends to create an open-source database for investigators. Therefore, a major part of the data collection is aligned with an existing national intensive care data registry and two international COVID-19 data collection initiatives. Additionally, we create a flexible design, so that additional measures can be added during the ongoing study based on new knowledge obtained from the rapidly growing body of evidence. The spread of the COVID-19 pandemic requires the swift implementation of observational research to unravel heterogeneity of the natural course of the disease of SARS-CoV-2 infection in mechanically ventilated patients. Our study design is expected to enhance aetiological, diagnostic and prognostic understanding of the disease. This paper describes the design of the MaastrICCht., Ethics and Dissemination: Ethical approval has been obtained from the medical ethics committee (Medisch Ethische Toetsingscommissie 2020-1565/3 00 523) of the Maastricht University Medical Centre+ (Maastricht UMC+), which will be performed based on the Declaration of Helsinki. During the pandemic, the board of directors of Maastricht UMC+ adopted a policy to inform patients and ask their consent to use the collected data and to store serum samples for COVID-19 research purposes. All study documentation will be stored securely for fifteen years after recruitment of the last patient. The results will be published in peer-reviewed academic journals, with a preference for open access journals, while particularly considering deposition of the manuscripts on a preprint server early., Trial Registration Number: The Netherlands Trial Register (NL8613)., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2020. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

To report on our clinical experience using EIT in individualized PEEP titration in ARDS. Using EIT assessment, we optimized PEEP settings in 39 ARDS patients. The EIT PEEP settings were compared with the physicians' PEEP settings and the PEEP settings according to the ARDS network. We defined a PEEP difference equal to or greater than 4 cm H 2 O as clinically relevant. Changes in lung compliance and PaO 2 /FiO 2 -ratio were compared in patients with EIT-based PEEP adjustments and in patients with unaltered PEEP. In 28% of the patients, the difference in EIT-based PEEP and physician-PEEP was clinically relevant; in 36%, EIT-based PEEP and physician-PEEP were equal. The EIT-based PEEP disagreed with the PEEP settings according to the ARDS network. Adjusting PEEP based upon EIT led to a rapid increase in lung compliance and PaO 2 /FiO 2 -ratio. However, this increase was also observed in the group where the PEEP difference was less than 4 cm H 2 O. We hypothesize that this can be attributed to the alveolar recruitment during the PEEP trial. EIT based individual PEEP setting appears to be a promising method to optimize PEEP in ARDS patients. The clinical impact, however, remains to be established.

[This corrects the article DOI: 10.1371/journal.pone.0194222.].

Background: Serum anti-glycan antibodies are a promising tool for differential diagnosis, disease stratification and prediction of Crohn's disease (CD). To investigate possible heritability of the markers we assessed the presence of serum anti-glycan antibodies in affected and unaffected relatives of patients with CD., Methods: Serum samples of 169 IBD patients of the German inflammatory bowel disease (IBD) network (140 CD & 29 Ulcerative colitis (UC)), 349 relatives of CD patients, 63 relatives of UC patients and 46 healthy controls were tested for the presence of anti-glycan antibodies by ELISA in a blinded fashion. Clinical data of the IBD patients and controls were available., Results: A higher proportion of non-affected CD relatives was positive for anti-glycan antibodies compared to healthy subjects. No inheritance of a specific pattern of anti-glycan antibodies could be detected. No difference in marker expression depending on the degree of relationship in the non-affected relatives was noted and the presence of family history did not lead to a difference in marker levels in the affected CD subjects., Conclusions: Non-affected CD relatives had a higher frequency of anti-glycan antibodies compared to healthy subjects. This difference was mild and was found to be true for the overall reactivity to glycan antigens, but not for specific patterns. This may indicate an inherited mechanism resulting in a non-specific increased reactivity to microbial antigens in IBD.

Introduction: It is widely accepted that transportation of critically ill patients is high risk. Unfortunately, however, there are currently no evidence-based criteria with which to determine the quality of various interhospital transport systems and their impact on the outcomes for patients. We aim to rectify this by assessing 2 scores which were developed in our hospital in a prospective, observational study. Primarily, we will be examining the Quality of interhospital critical care transportation in the Euregion Meuse-Rhine (QUIT EMR) score, which focuses on the quality of the transport system, and secondarily the SEMROS (Simplified EMR outcome score) which detects changes in the patient's clinical condition in the 24 hours following their transportation., Methods and Analysis: A web-based application will be used to document around 150 pretransport, intratransport and post-transport items of each patient case.To be included, patients must be at least 18-years of age and should have been supervised by a physician during an interhospital transport which was started in the study region.The quality of the QUIT EMR score will be assessed by comparing 3 predefined levels of transport facilities: the high, medium and low standards. Subsequently, SEMROS will be used to determine the effect of transport quality on the morbidity 24 hours after transportation.It is estimated that there will be roughly 3000 appropriate cases suitable for inclusion in this study per year. Cases shall be collected from 1 April 2015 until 31 December 2017., Ethics and Dissemination: This trial was approved by the Ethics committees of the university hospitals of Maastricht (Netherlands) and Aachen (Germany). The study results will be published in a peer reviewed journal. Results of this study will determine if a prospective randomised trial involving patients of various categories being randomly assigned to different levels of transportation system shall be conducted., Trial Registration Number: NTR4937., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.)

A 73-year-old male suffers a type-2 inferior myocardial infarction and is found unconscious, hypotensive and centrally cyanotic. His arterial blood gas analysis shows a chocolate-brown discoloration, with pO2 45.1 kPa, HbO2 48.9%, MetHb 51%, BE -9 and a lactate of 3.7 mmol/l. Administration of 200 mg of methylene blue intravenously, normalizes the patient's abnormalities. His life-threatening acquired methaemoglobinaemia appears secondary to under-the-counter viagra., (© The European Society of Cardiology 2015.)

Radiation survey instrumentation is adequate for the use around high-energy accelerators if capable to measure the dose arising from neutrons with energies ranging from thermal up to a few gigaelectronvolts. The SmartREM-LINUS is a commercial extended range rem-counter, consisting of a central (3)He-proportional counter surrounded by a spherical moderator made of borated polyethylene with an internal shield made of lead. The dose rate indicated by the SmartREM-LINUS was investigated for two different irradiation conditions. The linearity and the angular dependence of the indicated dose rate were investigated using reference neutron fields produced by (241)AmBe and (252)Cf. Additional measurements were performed in two different workplace fields with a component of neutrons with energies >20 MeV, namely the CERN-EU high-energy reference field and near the beam dump of the SwissFEL injector test facility. The measured dose rates were compared to a commercial rem-counter (WENDI2) and the results of Monte Carlo simulations., (© The Author 2016. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)

A novel and portable extracorporeal CO2-removal device was evaluated to provide additional gas transfer, auxiliary to standard therapy in severe acute hypercapnic respiratory failure. A dual-lumen catheter was inserted percutaneously in five subjects (mean age 55 ± 0.4 years) and, subsequently, connected to the CO2-removal device. The median duration on support was 45 hours (interquartile range 26-156), with a blood flow rate of approximately 500 mL/min. The mean PaCO2 decreased from 95.8 ± 21.9 mmHg to 63.9 ± 19.6 mmHg with the pH improving from 7.11 ± 0.1 to 7.26 ± 0.1 in the initial 4 hours of support. Three subjects were directly weaned from the CO2-removal device and mechanical ventilation, one subject was converted to ECMO and one subject died following withdrawal of support. No systemic bleeding or device complications were observed. Low-flow CO2 removal adjuvant to standard therapy was effective in steadily removing CO2, limiting the progression of acidosis in subjects with severe acute hypercapnic respiratory failure., (© The Author(s) 2015.)

Background: Potassium channels have been shown to determine wound healing in different tissues, but their role in intestinal epithelial restitution--the rapid closure of superficial wounds by intestinal epithelial cells (IEC)--remains unclear., Methods: In this study, the regulation of IEC migration by potassium channel modulation was explored with and without additional epidermal growth factor (EGF) under baseline and interferon-γ (IFN-γ)-pretreated conditions in scratch assays and Boyden chamber assays using the intestinal epithelial cell lines IEC-18 and HT-29. To identify possibly involved subcellular pathways, Western Blot (WB)-analysis of ERK and Akt phosphorylation was conducted and PI3K and ERK inhibitors were used in scratch assays. Furthermore, mRNA-levels of the potassium channel KCNN4 were determined in IEC from patients suffering from inflammatory bowel diseases (IBD)., Results: Inhibition of Ca(2+)-dependent potassium channels significantly increased intestinal epithelial restitution, which could not be further promoted by additional EGF. In contrast, inhibition of KCNN4 after pretreatment with IFN-γ led to decreased or unaffected migration. This effect was abolished by EGF. Changes in Akt, but not in ERK phosphorylation strongly correlated with these findings and PI3K but not ERK inhibition abrogated the effect of KCNN4 inhibition. Levels of KCNN4 mRNA were higher in samples from IBD patients compared with controls., Conclusions: Taken together, we demonstrate that inhibition of KCNN4 differentially regulates IEC migration in IFN-γ-pretreated vs. non pretreated conditions. Moreover, our data propose that the PI3K signaling cascade is responsible for this differential regulation. Therefore, we present a cellular model that contributes new aspects to epithelial barrier dysfunction in chronic intestinal inflammation, resulting in propagation of inflammation and symptoms like ulcers or diarrhea.

Venovenous extracorporeal membrane oxygenation (vv-ECMO) is a highly invasive method for organ support that is gaining in popularity due to recent technical advances and its successful application in the recent H1N1 epidemic. Although running a vv-ECMO program is potentially feasible for many hospitals, there are many theoretical concepts and practical issues that merit attention and require expertise. In this review, we focus on indications for vv-ECMO, components of the circuit, and management of patients on vv-ECMO. Concepts regarding oxygenation and decarboxylation and how they can be influenced are discussed. Day-to-day management, weaning, and most frequent complications are covered in light of the recent literature.

Objectives: To evaluate short-term outcomes and mortality after interhospital transportation of intensive care patients performed by a mobile intensive care unit (MICU)., Setting: This study was performed in the tertiary care process of interhospital transportation using the local MICU system in the South East of the Netherlands., Participants: Between March 2009 and December 2011, all transports of adult patients being performed by the local MICU centre have been documented; data on 42 variables, including a 24 h follow-up Sequential Organ Failure Assessment (SOFA) score of 368 consecutive interhospital transports of intensive care patients, were recorded. In 24 cases, the follow-up SOFA score was missing, so 344 data sets were included., Interventions: No interventions have been done., Primary/secondary Outcome Measures: Primary outcome measures were the mean SOFA score before and 24 h after transport, and the 24 h post-transport mortality. Moreover, the differences between the groups of 24 h post-transport survivors and non-survivors have been analysed., Results: The mean SOFA score before transport was 8.8 for the whole population and 8.6 for those patients who were alive 24 h after transport, with a mean SOFA score of 8.4 after transport. The adverse events rate was 6.4%. Fourteen patients (4.1%) died within 24 h after transport. Patients in this group had a higher SOFA score, lower pH, higher age and more additional medical support devices than those patients in the survivor group., Conclusions: The non-significant decrease in the post-transport SOFA score and the lack of an association between transport and 24 h post-transport mortality indicates that in the study setting, interhospital transportation of intensive care patients performed by a MICU system was not associated with a clinically relevant deterioration of the patient., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.)

Background & Aims: There is a need for a scoring system that provides a comprehensive assessment of structural bowel damage, including stricturing lesions, penetrating lesions, and surgical resection, for measuring disease progression. We developed the Lémann Index and assessed its ability to measure cumulative structural bowel damage in patients with Crohn's disease (CD)., Methods: We performed a prospective, multicenter, international, cross-sectional study of patients with CD evaluated at 24 centers in 15 countries. Inclusions were stratified based on CD location and duration. All patients underwent clinical examination and abdominal magnetic resonance imaging analyses. Upper endoscopy, colonoscopy, and pelvic magnetic resonance imaging analyses were performed according to suspected disease locations. The digestive tract was divided into 4 organs and subsequently into segments. For each segment, investigators collected information on previous operations, predefined strictures, and/or penetrating lesions of maximal severity (grades 1-3), and then provided damage evaluations ranging from 0.0 (no lesion) to 10.0 (complete resection). Overall level of organ damage was calculated from the average of segmental damage. Investigators provided a global damage evaluation (from 0.0 to 10.0) using calculated organ damage evaluations. Predicted organ indexes and Lémann Index were constructed using a multiple linear mixed model, showing the best fit with investigator organ and global damage evaluations, respectively. An internal cross-validation was performed using bootstrap methods., Results: Data from 138 patients (24, 115, 92, and 59 with upper tract, small bowel, colon/rectum, and anus CD location, respectively) were analyzed. According to validation, the unbiased correlation coefficients between predicted indexes and investigator damage evaluations were 0.85, 0.98, 0.90, 0.82 for upper tract, small bowel, colon/rectum, anus, respectively, and 0.84 overall., Conclusions: In a cross-sectional study, we assessed the ability of the Lémann Index to measure cumulative structural bowel damage in patients with CD. Provided further successful validation and good sensitivity to change, the index should be used to evaluate progression of CD and efficacy of treatment., (Copyright © 2015 AGA Institute. Published by Elsevier Inc. All rights reserved.)

This manuscript is a very general and non-political review on major issues concerning the evolving structural and organizational aspects of intensive care medicine, which may influence the outcomes of patients. It merely raises a multitude of issues, which deserve discussion in the different contexts of countries or communities.

Background: From data collected during the third International Study on Mechanical Ventilation (ISMV), we compared data from a Dutch cohort with a European cohort. We hypothesised that tidal volumes were smaller and applied positive end-expiratory pressure (PEEP) was higher in the Netherlands, compared with the European cohort. We also compared use of non-invasive ventilation (NIV) and outcomes in both cohorts., Methods: A post-hoc analysis of a prospective observational study of patients receiving mechanical ventilation., Results: Tidal volumes were smaller (7.6 vs. 8.1 ml÷kg predicted bodyweight) in the Dutch cohort and applied PEEP was higher (8 vs. 6 cm H2O). Fewer patients admitted in the Netherlands received NIV as first mode of mechanical ventilation (7.1 vs. 16.7%). Fewer patients in the Dutch cohort developed an ICU-acquired pneumonia (4.5 vs. 12.3%, p < 0.01) and sepsis (5.7 vs. 10.9%, p = 0.03), but more patients were diagnosed as having delirium (15.8 vs. 4.6%, p < 0.01). ICU and in-hospital mortality rates were 19% and 25%, respectively, in Dutch ICUs vs. 26% and 33% in Europe (p = 0.06 and 0.03)., Conclusion: Tidal volumes were smaller and applied PEEP was higher in the Dutch cohort compared with international data, but both Dutch and international patients received larger tidal volumes than recommended for prevention or treatment of acute respiratory distress syndrome. NIV as first mode of mechanical ventilation is less commonly used in the Netherlands. The incidence of ICU-acquired pneumonia is lower and of delirium higher in the Netherlands compared with international data.

Background: Markers that predict the occurrence of a complicated disease behavior in patients with Crohn's disease (CD) can permit a more aggressive therapeutic regimen for patients at risk. The aim of this cohort study was to test the blood levels of hemoglobin (Hgb) and hematocrit (Hct) for the prediction of complicated CD behavior and CD related surgery in an adult patient population., Methods: Blood samples of 62 CD patients of the German Inflammatory Bowel Disease-network "Kompetenznetz CED" were tested for the levels of Hgb and Hct prior to the occurrence of complicated disease behavior or CD related surgery. The relation of these markers and clinical events was studied using Kaplan-Meier survival analysis and adjusted COX-proportional hazard regression models., Results: The median follow-up time was 55.8 months. Of the 62 CD patients without any previous complication or surgery 34% developed a complication and/or underwent CD related surgery. Low Hgb or Hct levels were independent predictors of a shorter time to occurrence of the first complication or CD related surgery. This was true for early as well as late occurring complications. Stable low Hgb or Hct during serial follow-up measurements had a higher frequency of complications compared to patients with a stable normal Hgb or Hct, respectively., Conclusions: Determination of Hgb or Hct in complication and surgery naïve CD patients might serve as an additional tool for the prediction of complicated disease behavior.

Background: Vidofludimus (SC12267) is a novel oral immunomodulator inhibiting dihydroorotate dehydrogenase (DHODH) and the expression of proinflammatory cytokines including interleukin-17 (IL17A and IL17F) and interferon-gamma. The objective of the study was to explore the efficacy, safety and tolerability of vidofludimus in steroid-dependent inflammatory bowel disease (IBD)., Methods: The open label uncontrolled ENTRANCE study (ClinicalTrials.gov NCT00820365) has been conducted at 13 study centers in Germany, Bulgaria and Romania. Thirty-four steroid-dependent patients with a confirmed diagnosis of Crohn's disease (CD) or ulcerative colitis (UC) were treated with a once daily 35mg oral dose of vidofludimus over 12weeks. Steroids were tapered during the first 8weeks followed by a steroid-free treatment period of 4weeks. Complete response was defined as steroid-free clinical remission at week 12; partial response was defined as being in remission at steroid dose equal or lower than the individual patient's threshold dose for relapse., Results: Of the thirty-four patients enrolled in this trial 26 were evaluable for primary efficacy assessment. After completion of the 12weeks treatment phase 8 out of 14 (57.1%) patients with CD and 6 out of 12 (50.0%) patients with UC were in steroid-free remission (complete responders). Another 4 (28.6%) patients in CD and 5 (41.7%) patients in UC were partial responders. Vidofludimus was well tolerated, no drug-related serious adverse events were observed., Conclusions: This trial provides first evidence of clinical efficacy of vidofludimus in IBD. Although the safety and tolerability profile seems favorable, long-term controlled studies are needed to further investigate its potential as novel IBD therapy., (Copyright © 2012 European Crohn's and Colitis Organisation. Published by Elsevier B.V. All rights reserved.)

Background: The determination of end-tidal carbon dioxide (etCO2) is very helpful in cardiac resuscitation for confirmation and monitoring of endotracheal tube placement and as an indicator of return of circulation and effectiveness of chest compressions. There is now also widespread use of capnometry on-site at emergency and trauma fields., Objective: We studied the accuracy and correlation of three capnometers (EMMA, Medtronic, and Evita) with partial pressure of arterial CO2 (PaCO2) measurements., Methods: The three capnometers were placed in-line in the ventilator tubing of the patient. Forty sedated and mechanically ventilated post-cardiac surgery patients were studied. Twenty consecutive etCO2 values were collected simultaneously from all three monitors while drawing an arterial blood sample. Paired sample t-test and Pearson correlation were used to compare the capnometers and their correlation with PaCO2., Results: The correlation of etCO2 measurements between all three capnometers was good (Emma vs. Evita: 0.874, Emma vs. Medtronic: 0.949, Evita vs. Medtronic: 0.878). The correlation of PaCO2 with the Evita is the lowest (0.671) as compared to the EMMA (0.693) and the Medtronic (0.727). The lowest dispersion of the difference between etCO2 and PaCO2 was seen in EMMA (3.30), the highest in Evita (3.98)., Conclusions: A good correlation between etCO2 and PaCO2 was shown with the three capnometers in the present study. However, etCO2 measurements were not valid to estimate PaCO2 in these patients. Therefore, capnometry cannot be used to replace serial blood gas analyses completely, but may be a good cardiopulmonary trend monitor and alerting system in catastrophic events., (Copyright © 2013 Elsevier Inc. All rights reserved.)

Background and Aims: Leucocyte migration to gut mucosa, mediated by integrin binding to mucosal addressin cell adhesion molecule (MAdCAM), is a promising target for therapeutic intervention in inflammatory bowel disease. This first-in-human study of a monoclonal antibody to MAdCAM, PF-00547,659, aimed to explore the safety and preliminary efficacy of this gut-specific mechanism in ulcerative colitis., Methods: In this randomised, double-blind placebo-controlled study, 80 patients with active ulcerative colitis received single or multiple (three doses, 4-week intervals) doses of PF-00547,659 0.03-10 mg/kg IV/SC, or placebo. Safety was assessed by adverse events, laboratory tests, and immunogenicity. Exploratory efficacy analyses were based on Mayo score and endoscopic responder rates at weeks 4 and 12. Faecal calprotectin was quantified as a measure of disease activity, and the number of α₄β₇⁺ lymphocytes was measured to demonstrate drug activity., Results: No obvious drug-related side effects were observed in the PF-00547,659 group, while patient numbers, especially those fully exposed, were small. Overall responder/remission rates at 4 and 12 weeks were 52%/13% and 42%/22%, respectively with combined PF-00547,659 doses compared with 32%/11% and 21%/0%, respectively with placebo. Equivalent endoscopic responder rates were 50% and 42% versus 26% and 29%, respectively. Faecal calprotectin levels decreased to a greater extent with PF-00547,659 than placebo (week 4: 63% vs 18%). Despite variability, there was a trend for an increase in α₄β₇⁺ lymphocytes in patients receiving PF-00547,659., Conclusions: The favourable short-term safety profile and preliminary efficacy findings for PF-00547,659 in this first-in-human study pave the way for further investigation in larger trials, to establish the role of PF-00547,659 in ulcerative colitis treatment. Trial Register No: NCT00928681.

Background/aims: Some suggest MRI to be superior to ultrasound in Crohn's disease. We analyzed how often MR enterography (MRE) following a routine ultrasound leads to a change in therapeutic decision., Material and Methods: We retrospectively evaluated 47 patients with Crohn's disease undergoing routine ultrasound examination. Actual medical history, complete blood count, C-reactive protein (CRP), and sonographic findings were assessed independently by two specialists who retrospectively provided a therapeutic proposal. Additionally, all patients received MRE. Thereafter, the specialists had to provide a new therapeutic concept regarding all the available information., Results: Evaluation of the rectum was not successful by ultrasound, but MRE gave good results. Only 1 of 7 abscesses was identified sonographically. Three of the abscesses missed at sonography were localized in the perirectal/perianal region. MRE detected more inflamed bowel segments, but ultrasound assessment of anatomically fixed bowel parts showed good recognition by MRE. With increasing CRP values, we found more positive results of ultrasound and MRE. Therapeutic change was suggested in only 18 patients., Conclusions: Ultrasound should be performed by an experienced examiner, and a proctological examination should be added. MRE is justified in cases of discrepancy between clinical findings and the results of diagnostic ultrasound and, moreover, if Crohn's lesions are suspected at sites proximal to the terminal or neoterminal ileum., (Copyright © 2010 S. Karger AG, Basel.)

Background: Adenocarcinoma arising from perianal fistulae in patients with Crohn's disease (CD) is rare. The literature consists mainly of case reports and small series making characterization of this clinical entity difficult. We present 6 patients with CD and fistula-associated anal adenocarcinoma (FAAA) and a systematic review of published series., Methods: Retrospective charts were reviewed of 6 consecutive patients with FAAA in CD treated from 1992 through 2007. All available variables of our patients and of all available published cases were included for statistical analysis., Results: All patients treated at our institution had severe perianal CD at presentation. The average age at time of diagnosis was 45.5 years. All patients underwent abdominoperineal resection (APR) and 4 received chemoradiation. Four patients died with metastatic disease, 1 is alive with pelvic recurrence at 55 months, and 1 is alive without evidence of disease at 19 months follow-up. A total of 23 publications including 65 patients (37 female, mean age 53 years) with FAAA were reviewed in our systematic review. The average fistula duration was 14 years. Mean delay of cancer diagnosis was 11 months. APR was performed in 56 patients with an overall 3-year survival rate of 54%. Thirteen of 15 patients with node-positive tumors died with recurrent disease following surgery., Conclusions: Adenocarcinoma arising from long-standing perianal CD fistulae is being increasingly reported. The outcome is poor following operative treatment, especially if perirectal lymph nodes are involved. Periodical cancer surveillance should be performed in all patients with long-standing perianal CD fistulae.

Background: A high proportion of patients with Crohn's disease (CD) over time develop complications like fistulae and strictures, requiring surgery. We tested a panel of antiglycan antibodies for predicting the occurrence of complications and CD-related surgery in an adult patient cohort., Methods: Serum samples of 149 CD patients of the German inflammatory bowel disease (IBD) network were tested for the presence of anti-laminarin IgA (Anti-L), anti-chitin IgA (Anti-C), anti-chitobioside IgA (ACCA), anti-laminaribioside IgG (ALCA), anti-mannobioside IgG (AMCA), and anti-Saccaromyces cerevisiae IgG (gASCA) carbohydrate antibodies by enzyme-linked immunosorbent assay (ELISA) (IBDX(R) panel, Glycominds, Lod, Israel) in a blinded fashion. Clinical data were available on occurrence of complicated disease or CD-related surgery as well as disease activity, onset, and location., Results: The median follow-up of the patients without any previous complication or surgery at time of sample procurement was 53.7 months. Overall, 26.3% developed a complication and 17.1% underwent CD-related surgery, respectively. Positivity for gASCA, AMCA, ACCA, and Anti-L alone or an increasing frequency of positive serum antibodies independently predicted a faster progression toward a more severe disease course. Once a complication or surgery had occurred only positivity for Anti-L or more than 3 markers out of the whole panel indicated progression to an additional surgery or complication. The antibody status of most patients remained stable over time., Conclusions: This is the first study showing the clinical value of serum antiglycan antibodies for prediction of a more complicated disease course in adult patients with CD.

Importance of the Field: Inflammatory bowel diseases are chronic inflammatory diseases that comprise of two forms - Crohn's disease (CD) and ulcerative colitis (UC) - characterized by aberrant responses to luminal bacteria in genetically susceptible individuals. Whereas inflammation is limited to the large intestine in patients with UC, CD can affect all parts of the gastrointestinal tract. During disease exacerbations, pharmacological or surgical intervention is usually needed to re-establish remission; however, current therapeutic interventions cannot cure CD. As a subgroup of patients with CD will not be able to remain in remission with available drugs or suffer from side effects, new therapeutic strategies are needed., Areas Covered in This Review: This review focuses on emerging drugs in the treatment of CD and reviews data on their efficacy and safety. An extensive review of the available literature was undertaken using MEDLINE to identify relevant studies., What the Reader Will Gain: The reader will learn about current therapeutic strategies in patients with CD and gain insights into emerging new drugs., Take Home Message: As modification of the clinical course of CD becomes the therapeutic paradigm, potential future treatments have to induce mucosal healing in order to prevent long-term complications. New biologics show promising results.