Observational pilot study on the influence of an app-based self-management program on the quality of life of women with endometriosis.

PURPOSE: Endometriosis can significantly impair the quality of life of those affected. Multimodal self-help measures are recommended but often difficult to access. Smartphone apps have been shown to improve the quality of life for other conditions with chronic pain. The aim of this study was to examine whether there is evidence of beneficial effects of the smartphone app "Endo-App®" and whether a multicenter randomized controlled trial should be planned to substantiate these effects. METHODS: In a sample of N = 106 women affected by endometriosis the present study determined the influence of the use of Endo-App® on their quality of life. Among others, the validated questionnaire Endometriosis Health Profile from Oxford University was used for this purpose. RESULTS: The use of Endo-App® lead to a highly significant improvement in quality of life already after 2 weeks. A statistically significant change was found for nine out of ten measured variables of quality of life. A series of further analyses validated that the measured positive effects were not due to other confounding factors. CONCLUSION: In summary, the results indicate that the quality of life of women with endometriosis improved by the digital self-management tool Endo-App®. More studies are needed to further explore the influence of the app on quality of life and as confirmatory evidence of beneficial effects. For this purpose, a randomized controlled trial should be conducted over a longer period of time. TRIAL REGISTRATION: This trial is registered at clinicaltrials.gov under the registration number NCT05528601 on August 18, 2022. It was retrospectively registered.

A comparison of conventional and advanced 3D imaging techniques for percutaneous left atrial appendage closure.

Background: Understanding complex cardiac anatomy is essential for percutaneous left atrial appendage (LAA) closure. Conventional multi-slice computed tomography (MSCT) and transesophageal echocardiography (TEE) are now supported by advanced 3D printing and virtual reality (VR) techniques for three-dimensional visualization of volumetric data sets. This study aimed to investigate their added value for LAA closure procedures. Methods: Ten patients scheduled for interventional LAA closure were evaluated with MSCT and TEE. Patient-specific 3D printings and VR models were fabricated based on MSCT data. Ten cardiologists then comparatively assessed LAA anatomy and its procedure relevant surrounding structures with all four imaging modalities and rated their procedural utility on a 5-point Likert scale questionnaire (from 1 = strongly agree to 5 = strongly disagree). Results: Device sizing was rated highest in MSCT (MSCT: 1.9 ± 0.8; TEE: 2.6 ± 0.9; 3D printing: 2.5 ± 1.0; VR: 2.5 ± 1.1; p < 0.01); TEE, VR, and 3D printing were superior in the visualization of the Fossa ovalis compared to MSCT (MSCT: 3.3 ± 1.4; TEE: 2.2 ± 1.3; 3D printing: 2.2 ± 1.4; VR: 1.9 ± 1.3; all p < 0.01). The major strength of VR and 3D printing techniques was a superior depth perception (VR: 1.6 ± 0.5; 3D printing: 1.8 ± 0.4; TEE: 2.9 ± 0.7; MSCT: 2.6 ± 0.8; p < 0.01). The visualization of extracardiac structures was rated less accurate in TEE than MSCT (TEE: 2.6 ± 0.9; MSCT: 1.9 ± 0.8, p < 0.01). However, 3D printing and VR insufficiently visualized extracardiac structures in the present study. Conclusion: A true 3D visualization in VR or 3D printing provides an additional value in the evaluation of the LAA for the planning of percutaneous closure. In particular, the superior perception of depth was seen as a strength of a 3D visualization. This may contribute to a better overall understanding of the anatomy. Clinical studies are needed to evaluate whether a more comprehensive understanding through advanced multimodal imaging of patient-specific anatomy using VR may translate into improved procedural outcomes.

Attenuating the Polysulfide Shuttle Mechanism by Separator Coating.

Lithium-sulfur batteries have a high energy density but lack cycle stability to reach market maturity. This is mainly due to the polysulfide shuttle mechanism, i. e., the leaching of active material from the cathode into the electrolyte and subsequent side reactions. We demonstrate how to attenuate the polysulfide shuttle by magnetron sputtering molybdenum oxysulfide, manganese oxide, and chromium oxide onto microporous polypropylene separators. The morphology of the amorphous coatings was analyzed by SEM and XRD. Electrochemical cyclization quantified how these coatings improved Coulombic efficiency and cycle stability. These tests were conducted in half cells. We compare the different performances of the different coatings with the known chemical and adsorption properties of the respective coating materials.

Trends in Molecular Diagnosis of Nosocomial Pneumonia Classic PCR vs. Point-of-Care PCR: A Narrative Review.

Nosocomial pneumonia is one of the most frequent hospital-acquired infections. One of the types of nosocomial pneumonia is ventilator-associated pneumonia, which occurs in endotracheally intubated patients in intensive care units (ICU). Ventilator-associated pneumonia may be caused by multidrug-resistant pathogens, which increase the risk of complications due to the difficulty in treating them. Pneumonia is a respiratory disease that requires targeted antimicrobial treatment initiated as early as possible to have a good outcome. For the therapy to be as specific and started sooner, diagnostic methods have evolved rapidly, becoming quicker and simpler to perform. Polymerase chain reaction (PCR) is a rapid diagnostic technique with numerous advantages compared to classic plate culture-based techniques. Researchers continue to improve diagnostic methods; thus, the newest types of PCR can be performed at the bedside, in the ICU, so-called point of care testing-PCR (POC-PCR). The purpose of this review is to highlight the benefits and drawbacks of PCR-based techniques in managing nosocomial pneumonia.

A Recurrent Neural Network Model for Predicting Activated Partial Thromboplastin Time After Treatment With Heparin: Retrospective Study.

BACKGROUND: Anticoagulation therapy with heparin is a frequent treatment in intensive care units and is monitored by activated partial thromboplastin clotting time (aPTT). It has been demonstrated that reaching an established anticoagulation target within 24 hours is associated with favorable outcomes. However, patients respond to heparin differently and reaching the anticoagulation target can be challenging. Machine learning algorithms may potentially support clinicians with improved dosing recommendations. OBJECTIVE: This study evaluates a range of machine learning algorithms on their capability of predicting the patients' response to heparin treatment. In this analysis, we apply, for the first time, a model that considers time series. METHODS: We extracted patient demographics, laboratory values, dialysis and extracorporeal membrane oxygenation treatments, and scores from the hospital information system. We predicted the numerical values of aPTT laboratory values 24 hours after continuous heparin infusion and evaluated 7 different machine learning models. The best-performing model was compared to recently published models on a classification task. We considered all data before and within the first 12 hours of continuous heparin infusion as features and predicted the aPTT value after 24 hours. RESULTS: The distribution of aPTT in our cohort of 5926 hospital admissions was highly skewed. Most patients showed aPTT values below 75 s, while some outliers showed much higher aPTT values. A recurrent neural network that consumes a time series of features showed the highest performance on the test set. CONCLUSIONS: A recurrent neural network that uses time series of features instead of only static and aggregated features showed the highest performance in predicting aPTT after heparin treatment.

Outcome Comparison of Acute Respiratory Distress Syndrome (ARDS) in Patients with Trauma-Associated and Non-Trauma-Associated ARDS: A Retrospective 11-Year Period Analysis.

(1) Background: Acute respiratory distress syndrome (ARDS) is a rare complication in multiply injured patients. Due to the rarity of ARDS development after trauma, little is known about outcomes of patients with trauma-associated ARDS compared to patients with non-trauma-associated ARDS. (2) Methods: This retrospective analysis included n = 1038 ARDS patients admitted to the ARDS center of Charité-Universitätsmedizin Berlin between 2007 and 2018. Patients with trauma-associated ARDS (n = 62) were compared to patients with non-trauma-associated ARDS (n = 976). In a secondary analysis, patients from the group with non-trauma-associated ARDS were 1:1 nearest neighbor matched to patients with trauma-associated ARDS. The primary outcomes were 28-day in-hospital mortality, 60-day in-hospital mortality, and overall in-hospital mortality. (3) Results: Overall in-hospital mortality in trauma-associated ARDS was 29.0% compared to 40.5% in all patients with non-trauma-associated ARDS (p = 0.074). The in-hospital mortality rate in matched patients with non-trauma-associated ARDS (33.9%) was comparable to the trauma-associated ARDS cohort (p = 0.701). Kaplan-Meier curves indicated time-sensitive variations in 28-day and 60-day in-hospital survival. (4) Conclusion: Mortality was not different in patients with trauma-associated ARDS compared to patients with non-trauma-associated ARDS. Survival rate in the Kaplan-Meier curves stabilized after the critical initial phase and throughout the further 60-day period in patients with trauma-associated ARDS compared to patients with non-trauma-associated ARDS. Since this divergence was less pronounced in the matched cohort, it may be related to the younger age, fewer comorbidities, and lower ARDS severity in patients with trauma-associated ARDS. Patients with trauma-associated ARDS remain a very different cohort compared to patients with non-trauma-associated ARDS. Therefore, the outcome comparison is limited, even after matching.

Rates of severe complications in patients undergoing colorectal surgery for deep endometriosis-a retrospective multicenter observational study.

INTRODUCTION: Surgical experience and hospital procedure volumes have been associated with the risk of severe complications in expert centers for endometriosis in France. However, little is known about other certified units in Central European countries. MATERIAL AND METHODS: This retrospective observational study included 937 women who underwent surgery for colorectal endometriosis between January 2018 and January 2020 in 19 participating expert centers for endometriosis. All women underwent complete excision of colorectal endometriosis by rectal shaving, discoid or segmental resection. Postoperative severe complications were defined as grades III-IV of the Clavien-Dindo classification system including anastomotic leakage, fistula, pelvic abscess and hematoma. Surgical outcomes of centers performing less than 40 (group 1), 40-59 (group 2) and ≥60 procedures (group 3) over a period of 2 years were compared. RESULTS: The overall complication rate of grade III and IV complications was 5.1% (48/937), with rates of anastomotic leakage, fistula formation, abscess and hemorrhage in segmental resection, discoid resection and rectal shaving, respectively, as follows: anastomotic leakage 3.6% (14/387), 1.4% (3/222), 0.6% (2/328); fistula formation 1.6% (6/387), 0.5% (1/222), 0.9%; (3/328); abscess 0.5% (2/387), 0% (0/222) and 0.6% (2/328); hemorrhage 2.1% (8/387), 0.9% (2/222) and 1.5% (5/328). Higher overall complication rates were observed for segmental resection (30/387, 7.8%) than for discoid (6/222, 2.7%, P = 0.015) or shaving procedures (12/328, 3.7%, P = 0.089). No significant correlation was observed between the number of procedures performed and overall complication rates (rSpearman  = -0.115; P = 0.639) with a high variability of complications in low-volume centers (group 1). However, an intergroup comparison revealed a significantly lower overall severe complication rate in group 3 than in group 2 (2.9% vs 6.9%; P = 0.017) without significant differences between other groups. CONCLUSIONS: A high variability in complication rates does exist in centers with a low volume of activity. Major complications may decrease with an increase in the volume of activity but this effect cannot be generally applied to all institutions and settings.

Impact of Musashi-1 and Musashi-2 Double Knockdown on Notch Signaling and the Pathogenesis of Endometriosis.

The stem cell marker and RNA-binding protein Musashi-1 is overexpressed in endometriosis. Musashi-1-siRNA knockdown in Ishikawa cells altered the expression of stem cell related genes, such as OCT-4. To investigate the role of both human Musashi homologues (MSI-1 and MSI-2) in the pathogenesis of endometriosis, immortalized endometriotic 12-Z cells and primary endometriotic stroma cells were treated with Musashi-1- and Musashi-2-siRNA. Subsequently, the impact on cell proliferation, cell apoptosis, cell necrosis, spheroid formation, stem cell phenotype and the Notch signaling pathway was studied in vitro. Using the ENDOMET Turku Endometriosis database, the gene expression of stem cell markers and Notch signaling pathway constituents were analyzed according to localization of the endometriosis lesions. The database analysis demonstrated that expression of Musashi and Notch pathway-related genes are dysregulated in patients with endometriosis. Musashi-1/2-double-knockdown increased apoptosis and necrosis and reduced stem cell gene expression, cell proliferation, and the formation of spheroids. Musashi silencing increased the expression of the anti-proliferation mediator p21. Our findings suggest the therapeutic potential of targeting the Musashi-Notch axis. We conclude that the Musashi genes have an impact on Notch signaling and the pathogenesis of endometriosis through the downregulation of proliferation, stemness characteristics and the upregulation of apoptosis, necrosis and of the cell cycle regulator p21.

[S2k guidelines for the diagnosis and treatment of endometriosis-Recommendations for pathology]. / S2k-Leitlinie Diagnostik und Therapie der Endometriose ­ Anforderungen an die Pathologie.

The present article summarises the recommendations for the handling, histopathological workup, diagnostics and reporting in surgical pathology of biopsies and resection specimens in patients with the clinical diagnosis of endometriosis. In addition to practical aspects of pathology, the guidelines also take into account the clinical requirements for histopathology for the optimal diagnosis and therapy of the patients.Based on the definition of endometriosis of the corpus uteri (adenomyosis uteri) most commonly used in the pathological literature, this was defined in the guidelines as the detection of the endometriosis focus in the myometrium at a distance from the endomyometrial border of a medium-sized visual field (100× magnification), which in metric units corresponds to around 2.5 mm. In bowel resection specimens, the status of the resection margins had to be documented within the histopathological report.Also mentioned are the requirements for the reporting of carcinomas associated with endometriosis, including the immunohistochemical evaluation of steroid hormone receptors and mismatch repair proteins.

Cardiovascular Evaluation of Liver Transplant Patients by Using Coronary Calcium Scoring in ECG-Synchronized Computed Tomographic Scans.

BACKGROUND: The goal of cardiac evaluation of patients awaiting orthotopic liver transplantation (OLT) is to identify the patients at risk for cardiovascular events (CVEs) in the peri- and postoperative periods by opportunistic evaluation of coronary artery calcium (CAC) in non-gated abdominal computed tomographs (CT). METHODS: We hypothesized that in patients with OLT, a combination of Lee's revised cardiac index (RCRI) and CAC scoring would improve diagnostic accuracy and prognostic impact compared to non-invasive cardiac testing. Therefore, we retrospectively evaluated 169 patients and compared prediction of CVEs by both methods. RESULTS: Standard workup identified 22 patients with a high risk for CVEs during the transplant period, leading to coronary interventions. Eighteen patients had a CVE after transplant and a CAC score > 0. The combination of CAC and RCRI ≥ 2 had better negative (NPV) and positive predictive values (PPV) for CVEs (NPV 95.7%, PPV 81.6%) than standard non-invasive stress tests (NPV 92.0%, PPV 54.5%). CONCLUSION: The cutoff value of CAC > 0 by non-gated CTs combined with RCRI ≥ 2 is highly sensitive for identifying patients at risk for CVEs in the OLT population.

Case Report: Acute Splenic Artery Thrombosis in a COVID 19, Postpartum Patient.

The incidence of thromboembolic disease is reported to be high in SARS-CoV2 disease. Pregnancy, an already physiologically hypercoagulable state, associated to COVID 19, generates even more concern regarding the potentially increased risk of thrombotic events. The exact incidence of such complications is yet unknown, but there is data suggesting that coagulopathy and thromboembolism are both increased in pregnancies affected by COVID-19. Since the outbreak of the COVID 19 pandemics, the most common described thrombotic events associated with SARS-COV2 infection have been venous thromboembolism and disseminated intravascular coagulation, while arterial thrombotic events are less commonly described. Splenic infarction is a rare disorder that can be secondary to a hypercoagulable state. There are only few cases of splenic infraction described, but none with splenic artery thrombosis, in a post-partum patient, on therapeutic anticoagulation regimen. We present the case of a 31-year-old Caucasian, 26 weeks pregnant woman, with no prior medical history, admitted to the hospital with a severe form of COVID 19 pneumonia and who, during the course of the disease, developed a massive splenic infarction with splenic artery thrombosis.

The Significance of Duration of Exposure and Circulation of Fresh Air in SARS-CoV-2 Transmission Among Healthcare Workers.

Background: The true risk of infection after exposure to SARS-CoV-2 of healthcare workers (HCWs) in the workplace has not yet been established. This descriptive study analyzes the exposure characteristics of HCWs to SARS-CoV-2. Methods: In March 2020, at the beginning of the pandemic, a total of 58 HCWs in a regional hospital in Greece were exposed to three patients with symptomatic SARS-CoV-2 infection. These three index cases had taken part in an 8-day religious tour, during which 52 travelers spent 10 h every day in a tour bus. A study was made of the circumstances of the hospital exposure. Results: Of the 52 travelers in the bus, 48 contracted SARS-CoV2. None of the 58 HCW contacts developed symptoms related to COVID-19, although, 43% were exposed to a SARS-CoV-2 infected patient for more than 15 min, and 74% were within a distance of <1 m, and half of the contacts were not wearing a surgical mask. Additional information was that 63% of the contacts were exposed in a room sized more than 15 m2, and in more than 80% of cases, the window or the door to the room was open during their exposure. In about one-third of the exposure events, the HCW contacts were not wearing a mask and were at a distance of <1 m, and just under half of them were exposed for more than 15 min. One-fourth of the contacts underwent RT-PCR testing, and 11% IgG/IgM antibody testing for SARS-CoV-2, all of which were negative. All observed quarantine at home for 14 days. Conclusion: This observational study was made before the extent of the SARS-CoV-2 became apparent, and before routine preventive measures were observed by all HCWs. Comparing the conditions of exposure in the two different settings (bus vs. regional health facility), it is apparent that the duration of exposure and the small, enclosed nature of the bus are the distinguishing factors. In the healthcare setting, the elimination of both factors and the implementation of additional measures protected the exposed HCWs from contracting SARS-CoV-2 infection.

Image-derived mean velocity measurement for prediction of coronary flow reserve in a canonical stenosis phantom using magnetic particle imaging.

INTRODUCTION: Aim of this study is to evaluate whether magnetic particle imaging (MPI) is capable of measuring velocities occurring in the coronary arteries and to compute coronary flow reserve (CFR) in a canonical phantom as a preliminary study. METHODS: For basic velocity measurements, a circulation phantom was designed containing replaceable glass tubes with three varying inner diameters, matching coronary-vessel diameters. Standardised boluses of superparamagnetic-iron-oxide-nanoparticles were injected and visualised by MPI. Two image-based techniques were competitively applied to calibrate the respective glass tube and to compute the mean velocity: full-duration-at-half-maximum (FDHM) and tracer dilution (TD) method. For CFR-calculation, four necessary settings of the circulation model of a virtual vessel with an inner diameter of 4 mm were generated using differently sized glass tubes and a stenosis model. The respective velocities in stenotic glass tubes were computed without recalibration. RESULTS: On velocity level, comparison showed a good agreement (rFDHM = 0.869, rTD = 0.796) between techniques, preferably better for 4 mm and 6 mm inner diameter glass tubes. On CFR level MPI-derived CFR-prediction performed considerably inferior with a relative error of 20-44%. CONCLUSIONS: MPI has the ability to reliably measure coronary blood velocities at rest as well as under hyperaemia and therefore may be suitable for CFR calculation. Calibration-associated accuracy of CFR-measurements has to be improved substantially in further studies.

Epicardial fat, cardiovascular risk factors and calcifications in patients with chronic kidney disease.

BACKGROUND: Epicardial adipose tissue (EAT) exerts cardiopathogenic effects, but the independent association between EAT and cardiovascular (CV) calcification in patients with chronic kidney disease (CKD) remains controversial. We therefore assessed the association between EAT, CV risk factors and CV calcifications. METHODS: 257 patients with CKD Stage 3 and/or overt proteinuria underwent quantification of EAT, coronary artery calcification and aortic valve calcification by computed tomography. Framingham and American College of Cardiology and American Heart Association (ACC-AHA) 10-year CV event risk scores were calculated for each patient. RESULTS: Using multivariable regression analysis, higher EAT was significantly associated with the majority of investigated risk factors {higher age: odds ratio [OR] 1.05/year [95% confidence interval (CI) 1.02-1.08]; male sex: OR 4.03 [95% CI 2.22-7.31]; higher BMI: OR 1.28/kg/m2 [95% CI 1.20-1.37]; former smoking: OR 1.84 [95% CI 1.07-3.17]; lower high-density lipoprotein cholesterol: OR 0.98/mg/dL [95% CI 0.96-1.00] and lower estimated glomerular filtration rate: OR 0.98/mL/min/1.73 m2 [95% CI 0.97-0.99]; all P < 0.05} and was not associated with diabetes mellitus, hypertensive nephropathy, total cholesterol and albuminuria. EAT was positively associated with higher ACC-AHA and Framingham risk scores. EAT correlated with coronary artery calcification and aortic valve calcification [Spearman ρ = 0.388 (95% CI 0.287-0.532) and r rb = 0.409 (95% CI 0.310-0.556), respectively], but these correlations were dependent on CV risk factors. CONCLUSIONS: The increase of EAT can be explained by individual CV risk factors and kidney function and correlates with 10-year risk for CV event scores, suggesting that EAT is a modifiable risk factor in patients with CKD. Although EAT correlates with CV calcifications, these relations depend on CV risk factors.

Virtual Monoenergetic Images (VMI+) in Dual-Source Dual-Energy CT Venography (DSDE-CTV) of the Lower Extremity Prior to Coronary Artery Bypass Graft (CABG): A Feasibility Study.

RATIONALE AND OBJECTIVES: To evaluate the image quality and suitability of Dual-Source Dual-Energy CT venography (DSDE-CTV) with asynchronous virtual monoenergetic images (VMI+) of the entire lower extremity in the context of pre-surgical assessment of complex cases prior to coronary bypass graft as a feasibility study. MATERIALS AND METHODS: Fifteen consecutive patients, consisting of 5 females and 10 males with an average age of 52 ± 17 years underwent DSDE-CTV from the pubic symphysis to the ankles after intravenous injection of an iodinated contrast medium. DSDE-CTV was acquired with tube voltages of 80 kVp and sn140 kVp. Single spectrum images (A - 80 kVp; B - 140 kVp) as well as a linearly blended mixed data set (M_0.6) were reconstructed. By postprocessing, an VMI+ dataset at 40 keV was generated. Objective image quality parameters of the deep and superficial veins of thigh, knee, and calves were measured separately for each location. Signal-to-noise ratio (SNR) and contrast-to-noise ratio (CNR) were calculated. Additionally, subjective image quality was assessed independently by two radiologists. RESULTS: Mean vascular attenuation was 73.9 ± 17.8 HU at B, 113.7 ± 42.2 HU at M_0.6, 119.4 ± 45.5 HU at A, and 201.0 ± 89.7 HU at VMI+. Mean CNR was 6.7 ± 2.0 at 140 keV, 9.25 ± 2.3 in the M_0.6 datasets, 8.7 ± 3.0 at 80 keV, and 12.9 ± 4.3 at 40 keV. Attenuation values were approximately doubled when compared to the reference standard (M_0.6) with significantly improved SNR and CNR (p < 0.05). Subjective image quality scores were highest for VMI+ datasets (4.1 ± 0.5) and lowest for B datasets (2.3 ± 0.37), however differences between VMI+ datasets and M_0.6 datasets did not reach statistical significance. CONCLUSION: Postprocessing of dual-energy CTV with VMI+ significantly increases attenuation of veins and markedly improves SNR and CNR values, thereby improving the diagnostic quality of CTV for the evaluation of deep and superficial veins of the entire lower limb prior to coronary bypass graft.

New Large Animal Model for Aortic Aneurysms in the Viscerorenal Segment.

BACKGROUND: Aortic aneurysms in the viscerorenal-segment are nowadays treatable by endovascular means. Previously, new endograft techniques were only tested in healthy animals. We aimed to establish a new large animal model for testing complex endovascular stent techniques preclinically. METHODS: In sheep, four juxtarenal and two type IV thoracoabdominal aortic aneurysms were surgically created via a retroperitoneal approach. Two pieces out of a 10 × 15-cm bovine pericardial patch were sewn with the healthy aorta longitudinally. The viscerorenal segment was clamped, and the aorta was incised longitudinally. Then, the patches were longitudinally sewn together. In the meantime, antegrade flow through the native part of the aorta was already established by tangential clamping. Computed tomography angiography was performed after 4, 8, and 52 wk. RESULTS: Technical success was 100%. The median surgical procedure time was 3 h, the median blood loss was 210 mL, and the viscerorenal-segment clamping time was 2-4 min. The animals started drinking 1 h after arousal from anesthesia. One animal died after 1 wk because of delayed bleeding and another died after 1 y because of aneurysm rupture by a secondary bacterial infection. Four animals survived. The proximal landing zone diameter and the clock position of the vessel were stable over 52 wk. CONCLUSIONS: Surgical creation of an aortic aneurysm in the viscerorenal-segment in sheep was successful, without an ischemia/reperfusion injury. This animal model offers a new platform for evaluating innovative endovascular therapy options in vivo.

Exercise performance and symptoms in lowlanders with COPD ascending to moderate altitude: randomized trial.

OBJECTIVE: To evaluate the effects of altitude travel on exercise performance and symptoms in lowlanders with COPD. DESIGN: Randomized crossover trial. SETTING: University Hospital Zurich (490 m), research facility in mountain villages, Davos Clavadel (1,650 m) and Davos Jakobshorn (2,590 m). PARTICIPANTS: Forty COPD patients, Global Initiative for Obstructive Lung Disease (GOLD) grade 2-3, living below 800 m, median (quartiles) age 67 y (60; 69), forced expiratory volume in 1 second 57% predicted (49; 70). INTERVENTION: Two-day sojourns at 490 m, 1,650 m, and 2,590 m in randomized order. OUTCOME MEASURES: Six-minute walk distance (6MWD), cardiopulmonary exercise tests, symptoms, and other health effects. RESULTS: At 490 m, days 1 and 2, median (quartiles) 6MWD were 558 m (477; 587) and 577 m (531; 629). At 2,590 m, days 1 and 2, mean changes in 6MWD from corresponding day at 490 m were -41 m (95% CI -51 to -31) and -40 m (-53 to -27), n=40, P<0.05, both changes. At 1,650 m, day 1, 6MWD had changed by -22 m (-32 to -13), maximal oxygen uptake during bicycle exercise by -7% (-13 to 0) vs 490 m, P<0.05, both changes. At 490 m, 1,650 m, and 2,590 m, day 1, resting PaO2 were 9.0 (8.4; 9.4), 8.1 (7.5; 8.6), and 6.8 (6.3; 7.4) kPa, respectively, P<0.05 higher altitudes vs 490 m. While staying at higher altitudes, nine patients (24%) experienced symptoms or adverse health effects requiring oxygen therapy or relocation to lower altitude. CONCLUSION: During sojourns at 1,650 m and 2,590 m, lowlanders with moderate to severe COPD experienced a mild reduction in exercise performance and nearly one quarter required oxygen therapy or descent to lower altitude because of adverse health effects. The findings may help to counsel COPD patients planning altitude travel. REGISTRATION: ClinicalTrials.gov: NCT01875133.

ß-Nicotinamide Adenine Dinucleotide (ß-NAD) Inhibits ATP-Dependent IL-1ß Release from Human Monocytic Cells.

While interleukin-1ß (IL-1ß) is a potent pro-inflammatory cytokine essential for host defense, high systemic levels cause life-threatening inflammatory syndromes. ATP, a stimulus of IL-1ß maturation, is released from damaged cells along with ß-nicotinamide adenine dinucleotide (ß-NAD). Here, we tested the hypothesis that ß-NAD controls ATP-signaling and, hence, IL-1ß release. Lipopolysaccharide-primed monocytic U937 cells and primary human mononuclear leukocytes were stimulated with 2'(3')-O-(4-benzoyl-benzoyl)ATP trieethylammonium salt (BzATP), a P2X7 receptor agonist, in the presence or absence of ß-NAD. IL-1ß was measured in cell culture supernatants. The roles of P2Y receptors, nicotinic acetylcholine receptors (nAChRs), and Ca2+-independent phospholipase A2 (iPLA2ß, PLA2G6) were investigated using specific inhibitors and gene-silencing. Exogenous ß-NAD signaled via P2Y receptors and dose-dependently (IC50 = 15 µM) suppressed the BzATP-induced IL-1ß release. Signaling involved iPLA2ß, release of a soluble mediator, and nAChR subunit α9. Patch-clamp experiments revealed that ß-NAD inhibited BzATP-induced ion currents. In conclusion, we describe a novel triple membrane-passing signaling cascade triggered by extracellular ß-NAD that suppresses ATP-induced release of IL-1ß by monocytic cells. This cascade links activation of P2Y receptors to non-canonical metabotropic functions of nAChRs that inhibit P2X7 receptor function. The biomedical relevance of this mechanism might be the control of trauma-associated systemic inflammation.

Acute poisoning due to ingestion of Datura stramonium - a case report.

Datura stramonium (DS) is a widespread annual plant, containing atropine, hyoscyamine, and scopolamine, which can produce poisoning with a severe anticholinergic syndrome. Teenagers ingest the roots, seeds or the entire plant to obtain its hallucinogenic and euphoric effects. We presented the case of a 22 year old male who was admitted to the Emergency Room in a coma after consuming Datura stramonium, 2 hours earlier. The patient presented with fever, tachycardia with right bundle branch block, and urinary retention. Rapid sequence induction and intubation was performed immediately, with sedation and assisted-control mechanical ventilation, after being transferred to the Intensive Care Unit. The patient received activated charcoal, in repeated doses, external and internal cooling was applied, and an infusion of neostigmine was started. The biological assessment revealed rhabdomyolysis and prevention of renal failure was initiated. After a proper neurological evaluation, 36 hours after using Datura stramonium, the patient was extubated and transferred to the Psychiatric ward for further assessment and care.