The difference between arterial pCO2 and etCO2 after cardiac arrest - Outcome predictor or marker of unfavorable resuscitation circumstances?

INTRODUCTION: In former studies, the arterio-alveolar carbon dioxide gradient (ΔCO2) predicted in-hospital mortality after initially survived cardiac arrest. As early outcome predictors are urgently needed, we evaluated ΔCO2 as predictor for good neurological outcome in our cohort. METHODS: We retrospectively analyzed all patients ≥18 years of age after non-traumatic in- and out of hospital cardiac arrest in the year 2018 from our resuscitation database. Patients without advanced airway management, incomplete datasets or without return of spontaneous circulation were excluded. The first arterial pCO2 after admission and the etCO2 in mmHg at the time of blood sampling were recorded from patient's charts. We then calculated ΔCO2 (pCO2 - etCO2). For baseline analyses, ΔCO2 was dichotomized into a low and high group with separation at the median. Good neurological outcome on day 30, expressed as Cerebral Performance Category 1-2, defined our primary endpoint. Survival to 30 days was used as secondary endpoint. RESULTS: Out of 302 screened patients, 128 remained eligible for analyses. ΔCO2 was lower in 30-day survivors with good neurological outcome (12.2 mmHg vs. 18.8 mmHg, p = 0.009) and in 30-day survivors (12.5 mmHg vs. 20.0 mmHg, p = 0.001). In patients with high ΔCO2, a cardiac etiology of arrest was found less often. They had a higher body mass index, longer duration of resuscitation, higher amounts of epinephrine, lower pO2 levels but both higher pCO2 and blood lactate levels, resulting in lower blood pH and HCO3- levels at admission. In a crude binary logistic regression analysis, ΔCO2 was associated with 30-day neurological outcome (OR = 1.041 per mmHg of ΔCO2, 95% CI 1.008-1.074, p = 0.014). This association persisted after the adjustment for age, sex, witnessed arrest and shockable first rhythm. However, after addition of the duration of resuscitation or the cumulative epinephrine dosage to the model, ΔCO2 lost its association. CONCLUSION: ΔCO2 at admission after a successfully resuscitated cardiac arrest is associated with 30 days survival with good neurological outcome. However, a higher ΔCO2 may rather be a surrogate for unfavorable resuscitation circumstances than an independent outcome predictor.

Assessing the differential impact of chronic CMV and treated HIV infection on CD8+ T-cell differentiation in a matched cohort study: is CMV the key?

BACKGROUND: Cytomegalovirus (CMV) infection is one of the main driving forces of T-cell senescence in the general population, whereas its differential impact in people living with HIV (PLWH) is less well characterized. The study explores the effect of latent CMV infection on T-cell subsets, monocyte/macrophages activation markers, and CRP in PLWH on long-term ART. METHODS: Cross-sectional cohort study including PLWH on long-term suppressive ART. Individuals of 4 groups (HIV+CMV-, HIV+CMV+, HIV-CMV+, and HIV-CMV-) were matched 1:1:1:1 for age and sex. Immunophenotyping of lymphocyte and T-cell subsets by multicolor flow cytometry was performed in fresh blood samples collected from patients and healthy donors. RESULTS: Both, latent CMV and treated HIV infection were associated with an expansion of CD8 T cells, a reduced CD4/CD8 ratio, and with CD8 T-cell activation with a cumulative effect in CMV/HIV-coinfected individuals. CMV was associated with elevated numbers of late effector and terminally differentiated CD8 T-cells. Compared to CMV monoinfection, CMV/HIV coinfection showed to be associated with lower proportion of CD28-CD8+ T cells expressing CD57 suggesting that HIV preferentially expands CD28-CD57-CD8+ T cells and impedes terminal differentiation of CD28-CD8+ T cells. We could not show any association between HIV or CMV infection status and concentration of CRP and CD163. CONCLUSIONS: CMV infection is associated with phenotypic signs of T-cell senescence, promoting exacerbation and persistence of alterations of the T-cell compartment in PLWH on effective ART, which are associated with adverse clinical outcomes and may be an attractive target for therapeutic interventions.

Interrelations of Intraoperative Changes in Cerebral Tissue Oxygen Saturation with Brain Volumes and Neurodevelopment Outcome After the Comprehensive Stage II Procedure in Infants With Hypoplastic Left Heart Syndrome: A Retrospective Cohort Study.

OBJECTIVES: The monitoring of cerebral tissue oxygen saturation by near-infrared spectroscopy (ScerebO2) is used widely in pediatric cardiac anesthesia. However, little information is available on the effects of changes in perioperative ScerebO2 on brain morphology and neurologic outcome. The primary hypothesis tested in this study was that intraoperative ScerebO2 during the comprehensive stage II procedure correlated with brain volumes assessed by magnetic resonance imaging and neurodevelopmental scores. DESIGN: Retrospective observational cohort study. SETTING: University Hospital, Pediatric Heart Centre. PATIENTS AND MEASUREMENTS: In 19 infants, the intraoperative course of ScerebO2 during the comprehensive stage II procedure was examined. Minimal ScerebO2 and integrated ScerebO2 below 45% (AUC) during surgery, as well as cerebral magnetic resonance imaging (MRI) examinations and Bayley III test at the ages of two-to-three years, were analyzed. MAIN RESULTS: A positive correlation between minimal ScerebO2 and intracranial volume (p = 0.0243), total brain volume (p = 0.0243), and white matter volume (p = 0.0276) was observed, as was a negative correlation between AUC and intracranial volume (p = 0.0454) and white matter volume (p = 0.0381), respectively. No association was found between ScerebO2 and Bayley-III Score. CONCLUSION: The correlation between ScerebO2 and brain volumes measured by MRI pointed out a possible importance of neuroprotective strategies aimed at optimizing ScerebO2 during complex congenital heart surgery. That no correlation between ScerebO2 and Bayley III Score was found suggested multifactorial causes for neurologic outcome in children with congenital heart defects.

A higher reliability with a computed tomography scan-based three dimensional technique than with a two dimensional measurement for lower limb discrepancy in total hip arthroplasty planning.

PURPOSE: The goal was to compare the reliability of a novel 3D method with the standard 2D technique for lower limb discrepancy (LLD) measurement during pre-operative THA planning. METHODS: This prospective study included 100 consecutive patients who underwent THA using 3D planning based on a low-dose CT scan. The LLD was subdivided into three parameters: the intra-articular LLD (IA-LLD), the segmental extra-articular LLD (EA-LLD), and the total LLD (T-LLD). The LLD was assessed with a standard 2D technique on CT scanograms and also with a 3D method. A pelvic reference line (PBL) was determined as the 3D line joining the deepest part of the two great sciatic notches. The IA length was measured from the lesser trochanters (MLT) to the PBL. The EA length was measured from the MLT to the ankle center, and the total length was measured from the ankle center to the PBL. The intra- and inter-observer reliability of the measurements was assessed with the intra-class correlation coefficient (ICC). RESULTS: The intra-observer ICC was higher with the 3D technique for IA-LLD (0.96-0.97 vs. 0.79-0.84), EA-LLD (0.96 vs. 0.78-0.92), and T-LLD (0.99 vs. 0.90-0.97). Inter-observer ICC was also higher with the 3D technique for IA-LLD (0.90-0.94 vs. 0.70-0.84) and EA-LLD (0.93-0.96 vs. 0.80-0.82), but not for T-LLD (0.91-0.94 vs. 0.91-0.94). CONCLUSION: The presented 3D method has a higher reliability than 2D assessment of LLD during pre-operative THA planning. This article presents the first discussion of measuring LLD from 3D models. As 3D reconstruction becomes both more feasible and less-invasive, this study has interest to the orthopaedic surgeon.

Fremanezumab versus placebo for migraine prevention in patients with documented failure to up to four migraine preventive medication classes (FOCUS): a randomised, double-blind, placebo-controlled, phase 3b trial.

BACKGROUND: Antibodies targeting calcitonin gene-related peptide (CGRP) or its receptor have shown efficacy in the prevention of migraine attacks. We investigated the efficacy and tolerability of fremanezumab, a fully humanised CGRP antibody, in patients with migraine who had previously not responded to two to four classes of migraine preventive medications. METHODS: The randomised, double-blind, placebo-controlled, parallel-group, phase 3b FOCUS trial was done at 104 sites (including hospitals, medical centres, research institutes, and group practice clinics) across Belgium, the Czech Republic, Denmark, Finland, France, Germany, Italy, the Netherlands, Poland, Spain, Sweden, Switzerland, the UK, and the USA. We enrolled participants aged 18-70 years with episodic or chronic migraine who had documented failure to two to four classes of migraine preventive medications in the past 10 years. Failure was defined as no clinically meaningful improvement after at least 3 months of therapy at a stable dose, as per the treating physician's judgment; discontinuation because of adverse events that made treatment intolerable; or treatment contraindicated or unsuitable for the preventive treatment of migraine for the patient. Participants were randomly assigned (1:1:1) by electronic interactive response technology to subcutaneously administered quarterly fremanezumab (month 1, 675 mg; months 2 and 3: placebo), monthly fremanezumab (month 1: 225 mg in episodic migraine and 675 mg in chronic migraine; months 2 and 3: 225 mg in both migraine subgroups), or matched monthly placebo for 12 weeks. The primary outcome was mean change from baseline in the monthly average number of migraine days during the 12-week treatment period. This trial is registered with ClinicalTrials.gov, number NCT03308968, and is now completed. FINDINGS: Between Nov 10, 2017, and July 6, 2018, 838 participants with episodic (329 [39%]) or chronic (509 [61%]) migraine were randomly assigned to placebo (n=279), quarterly fremanezumab (n=276), or monthly fremanezumab (n=283). Reductions from baseline in monthly average migraine days over 12 weeks were greater versus placebo (least-squares mean [LSM] change -0·6 [SE 0·3]) with quarterly fremanezumab (LSM change -3·7 [0·3]; LSM difference vs placebo -3·1 [95% CI -3·8 to -2·4]; p<0·0001) and with monthly fremanezumab (LSM change -4·1 [0·34]; LSM difference vs placebo -3·5 [-4·2 to -2·8]; p<0·0001). Adverse events were similar for placebo and fremanezumab. Serious adverse events were reported in four (1%) of 277 participants with placebo, two (<1%) of 276 with quarterly fremanezumab, and four (1%) of 285 with monthly fremanezumab. INTERPRETATION: Fremanezumab was effective and well tolerated in patients with difficult-to-treat migraine who had previously not responded to up to four classes of migraine preventive medications. FUNDING: Teva Pharmaceuticals.

Six-Month Assessment of a Hand Prosthesis with Intraneural Tactile Feedback.

OBJECTIVE: Hand amputation is a highly disabling event, which significantly affects quality of life. An effective hand replacement can be achieved if the user, in addition to motor functions, is provided with the sensations that are naturally perceived while grasping and moving. Intraneural peripheral electrodes have shown promising results toward the restoration of the sense of touch. However, the long-term usability and clinical relevance of intraneural sensory feedback have not yet been clearly demonstrated. METHODS: To this aim, we performed a 6-month clinical study with 3 transradial amputees who received implants of transverse intrafascicular multichannel electrodes (TIMEs) in their median and ulnar nerves. After calibration, electrical stimulation was delivered through the TIMEs connected to artificial sensors in the digits of a prosthesis to generate sensory feedback, which was then used by the subjects while performing different grasping tasks. RESULTS: All subjects, notwithstanding their important clinical differences, reported stimulation-induced sensations from the phantom hand for the whole duration of the trial. They also successfully integrated the sensory feedback into their motor control strategies while performing experimental tests simulating tasks of real life (with and without the support of vision). Finally, they reported a decrement of their phantom limb pain and a general improvement in mood state. INTERPRETATION: The promising results achieved with all subjects show the feasibility of the use of intraneural stimulation in clinical settings. ANN NEUROL 2019;85:137-154.

TMEM41B is a novel regulator of autophagy and lipid mobilization.

Autophagy maintains cellular homeostasis by targeting damaged organelles, pathogens, or misfolded protein aggregates for lysosomal degradation. The autophagic process is initiated by the formation of autophagosomes, which can selectively enclose cargo via autophagy cargo receptors. A machinery of well-characterized autophagy-related proteins orchestrates the biogenesis of autophagosomes; however, the origin of the required membranes is incompletely understood. Here, we have applied sensitized pooled CRISPR screens and identify the uncharacterized transmembrane protein TMEM41B as a novel regulator of autophagy. In the absence of TMEM41B, autophagosome biogenesis is stalled, LC3 accumulates at WIPI2- and DFCP1-positive isolation membranes, and lysosomal flux of autophagy cargo receptors and intracellular bacteria is impaired. In addition to defective autophagy, TMEM41B knockout cells display significantly enlarged lipid droplets and reduced mobilization and ß-oxidation of fatty acids. Immunostaining and interaction proteomics data suggest that TMEM41B localizes to the endoplasmic reticulum (ER). Taken together, we propose that TMEM41B is a novel ER-localized regulator of autophagosome biogenesis and lipid mobilization.

Spatial distribution and incidence trend of human alveolar echinococcosis in southwest Germany: increased incidence and urbanization of the disease?

Ecology and epidemiology of Echinococcus multilocularis and human alveolar echinococcosis (AE) are changing in Central Europe. Our data from a regional referral center for AE in southwest Germany suggest rising regional incidence for AE (annual incidence per 100,000 population 2004-2011: 0.12; 2012-2019: 0.20) and emerging urban AE (of 7 cases of AE in Freiburg city dwellers none was diagnosed before 2012) calling for an intensification of E. multilocularis and AE surveillance and of AE prevention measures.

COVID-19 in people living with human immunodeficiency virus: a case series of 33 patients.

INTRODUCTION: Data on people living with human immunodeficiency virus (PLWH) in the current SARS-CoV-2 pandemic are still scarce. This case series of 33 PLWH patients with COVID-19 reveals symptoms and outcome in this special population. METHODS: Retrospective analysis of anonymized data including age, gender, HIV-associated parameters, symptoms, and outcome. RESULTS: Three out of 32 patients with documented outcomes died (9%). 91% of the patients recovered and 76% have been classified as mild cases. All patients were on antiretroviral treatment, of them 22 on tenofovir-containing regimen and 4 on the protease inhibitor darunavir. CONCLUSIONS: This preliminary case series does not support excess morbidity and mortality among symptomatic COVID-19 PLWH and with viral suppression on ART. SARS-CoV-2 infections may occur during boosted darunavir-based and/or on tenofovir-containing ART.

Anesthesia for bilateral pulmonary banding as part of hybrid stage I approach palliating neonates with hypoplastic left heart syndrome.

BACKGROUND: Neonatal management of patients with hypoplastic left heart syndrome and complex remains a challenging task, whereby the "hybrid" palliation is often reserved for high-risk patients as a "rescue" procedure. AIM: This study documents the anesthetic challenges and potential complications associated with the Giessen hybrid stage I approach. METHODS: The Giessen hybrid stage I approach is focused on surgical bilateral pulmonary artery banding. Retrospective perioperative data were analyzed. Contrary to a stable group A, inotropic treatment before surgery for treatment of postnatal shock classified patients as unstable (Group B). Clinical outcomes considered were inhospital mortality, duration of postoperative mechanical ventilation, postoperative time at the intensive care unit, perioperative vasoactive medication requirements, and red blood cell transfusion. RESULTS: From June 1998 to December 2015, 185 patients were allocated to Group A (n = 165) and Group B (n = 20). The inhospital mortality was 2.2% with no difference between the groups. There was also no difference in the postoperative time on mechanical ventilation and the time in the intensive care unit. Vasoactive medication was more often required in Group B (100%) compared to Group A (19%). In Group B, more red blood cells were transfused 6.0 ± 8.3 vs 2.0 ± 5.8 mL/kg in Group A (P < .05, 95% CI 0.0 - 2.6). CONCLUSION: Considering a learning curve, anesthesia for surgical bilateral pulmonary artery banding palliating patients with hypoplastic left heart syndrome and complex can safely be performed, independent from the preoperative clinical status.

The COSTA Study: Sternal Closure in High-Risk Patients - A Prospective Randomized Multicenter Trial.

BACKGROUND: Median sternotomy in patients with risk factors for wound healing is associated with high rates of postoperative wound infections and sternum instability. METHODS: A total of 338 patients with elective first median sternotomy and at least four predefined risk factors were randomized between Sternal Talon (Gebrüder Martin GmbH & Co. KG-KLS Martin Group, Tuttlingen, Germany) and wire cerclage. The primary end point was mediastinitis and/or sternal instability within 30 ± 5 days, and the secondary end points were mediastinitis and/or sternal instability within 60 ± 5 days; incidence of pneumonia during hospitalization within the first 30 (±5) days and chest pain intensity. RESULTS: The primary end point was reached in 10 Sternal Talon and 7 wire cerclage patients (6.2 vs. 4.7%, odds ratio [OR]: 1.3, 95% confidence interval [CI]: 0.5-3.6, p = 0.57) from 338 randomized patients. Sternal Talon group, n = 170 patients versus wire cerclage group, n = 168 patients. The differences between treatment groups with regard to the incidence of mediastinitis/sternum instability within the first 60 (±5) days after the primary sternum closure and the incidence of pneumonia during the hospitalization within the first 30 (±5) days were not statistically significant, either. We observed comparable rates of superficial surgical site infection (SSI) in Sternal Talon and wire cerclage patients (16.1 vs. 12.1%, OR: 1.4, 95% CI: 0.7-2.7, p = 0.31). CONCLUSION: According to these data, there is no statistically significant difference between Sternal Talon closure and wire cerclage in reducing the incidence of mediastinitis and superficial SSI after primary closure of median sternotomy in high-risk patients.

Control of basal jasmonate signalling and defence through modulation of intracellular cation flux capacity.

Unknown mechanisms tightly regulate the basal activity of the wound-inducible defence mediator jasmonate (JA) in undamaged tissues. However, the Arabidopsis fatty acid oxygenation upregulated2 (fou2) mutant in vacuolar two-pore channel 1 (TPC1D454N ) displays high JA pathway activity in undamaged leaves. This mutant was used to explore mechanisms controlling basal JA pathway regulation. fou2 was re-mutated to generate novel 'ouf' suppressor mutants. Patch-clamping was used to examine TPC1 cation channel characteristics in the ouf suppressor mutants and in fou2. Calcium (Ca2+ ) imaging was used to study the effects fou2 on cytosolic Ca2+ concentrations. Six intragenic ouf suppressors with near wild-type (WT) JA pathway activity were recovered and one mutant, ouf8, affected the channel pore. At low luminal calcium concentrations, ouf8 had little detectable effect on fou2. However, increased vacuolar Ca2+ concentrations caused channel occlusion, selectively blocking K+ fluxes towards the cytoplasm. Cytosolic Ca2+ concentrations in unwounded fou2 were found to be lower than in the unwounded WT, but they increased in a similar manner in both genotypes following wounding. Basal JA pathway activity can be controlled solely by manipulating endomembrane cation flux capacities. We suggest that changes in endomembrane potential affect JA pathway activity.

Identification of Small Molecules Which Induce Skeletal Muscle Differentiation in Embryonic Stem Cells via Activation of the Wnt and Inhibition of Smad2/3 and Sonic Hedgehog Pathways.

The multilineage differentiation capacity of mouse and human embryonic stem (ES) cells offers a testing platform for small molecules that mediate mammalian lineage determination and cellular specialization. Here we report the identification of two small molecules which drives mouse 129 ES cell differentiation to skeletal muscle with high efficiency without any genetic modification. Mouse embryoid bodies (EBs) were used to screen a library of 1,000 small molecules to identify compounds capable of inducing high levels of Pax3 mRNA. Stimulation of EBs with SMIs (skeletal muscle inducer, SMI1 and SMI2) from the screen resulted in a high percentage of intensively twitching skeletal muscle fibers 3 weeks after induction. Gene expression profiling studies that were carried out for mode of actions analysis showed that SMIs activated genes regulated by the Wnt pathway and inhibited expression of Smad2/3 and Sonic Hedgehog (Shh) target genes. A combination of three small molecules known to modulate these three pathways acted similarly to the SMIs found here, driving ES cells from 129 as well as Balb/c and C57Bl/6 to skeletal muscle. Taken together, these data demonstrate that the SMI drives ES cells to skeletal muscle via concerted activation of the Wnt pathway, and inhibition of Smad2/3 signaling and Shh pathways. This provides important developmental biological information about skeletal muscle differentiation from embryonic stem cells and may lead to the development of new therapeutics for muscle disease.

Application of Continuous Wound-Infusion Catheters in Lung Transplantation: A Retrospective Data Analysis.

Background Lung transplantation is the only treatment option for many patients with end-stage pulmonary disease. Therefore, postthoracotomy pain therapy is of vital interest. Thoracic epidural analgesia (EPI) is the "gold standard" for postthoracotomy pain, but especially in lung transplantation contraindications, and potential infectious complications limit its advantages. Under these circumstances surgically placed postthoracotomy catheter-assisted continuous paravertebral intercostal nerve block (PVB) could be of advantage. Methods We performed a retrospective cohort study of patients who underwent lung transplantation between 2005 and 2012. Groups were defined according to the type of postoperative pain therapy: PVB, EPI, and SYS (systemic analgesia). Total 44 patients were eligible. Results Postoperative opioid requirement of the PVB and EPI group was comparable and less than that of the SYS group. Patients of the PVB group were weaned earlier from mechanical ventilation after lung transplantation. Conclusion The potency of postoperative pain therapy of EPI and PVB seemed to be comparable and superior to SYS. Considering the risks and benefits, PVB could be a better choice than EPI for postthoracotomy pain therapy, especially in lung transplantation.

The provision of pediatric cardiac anesthesia services in Germany: current status of structural and personnel organization.

BACKGROUND: Anesthesia for pediatric cardiac surgery requires a high level of expert knowledge. There are currently no recommendations and standards for anesthetic management for congenital cardiac surgery in Germany. AIM: The aim of the present study was to assess the current status of structural and personnel anesthetic standards at pediatric cardiac surgery centers in Germany. METHODS: All cardiac surgical centers in Germany were reviewed for an active program for congenital heart surgery. Centers with an active program were invited to respond to an online survey. The questionnaire containing 55 items in 16 categories assessed current practice in pediatric cardiac anesthesia. RESULTS: An active program for pediatric cardiac surgery was identified at 27 centers. The response rate to the survey was 96.3%. A specialized group of anesthesiologists for pediatric cardiac anesthesia was reported from 26 centers (92.3%). The mean size of this group was 4.8 anesthesiologists per center. However, the annual case load of centers and relative annual case load per specialized anesthesiologist varied considerably between 12.5 and 250. Nonanesthesiologists performed sedation and general anesthesia for diagnostic and therapeutic interventions outside the operating theater in children with congenital heart diseases in 24 centers (77%). Although special equipment, for example, pediatric TEE, near-infrared spectroscopy, and devices for mechanical auto transfusion were available in most centers, their routine use was not always part of standard operating procedures. The proposal for mean adequate training in pediatric cardiac anesthesia as estimated by the participating centers was 10.8 months. CONCLUSION: The present study represents the current structural situation for anesthesia at German pediatric cardiac surgery centers.

Review: Ras GTPases and myosin: Qualitative conservation and quantitative diversification in signal and energy transduction.

Most GTPases and many ATPases belong to the P-loop class of proteins with significant structural and mechanistic similarities. Here we compare and contrast the basic properties of the Ras family GTPases and myosin, and conclude that there are fundamental similarities but also distinct differences related to their specific roles. © 2016 Wiley Periodicals, Inc. Biopolymers 105: 422-430, 2016.

Systems survey of endocytosis by multiparametric image analysis.

Endocytosis is a complex process fulfilling many cellular and developmental functions. Understanding how it is regulated and integrated with other cellular processes requires a comprehensive analysis of its molecular constituents and general design principles. Here, we developed a new strategy to phenotypically profile the human genome with respect to transferrin (TF) and epidermal growth factor (EGF) endocytosis by combining RNA interference, automated high-resolution confocal microscopy, quantitative multiparametric image analysis and high-performance computing. We identified several novel components of endocytic trafficking, including genes implicated in human diseases. We found that signalling pathways such as Wnt, integrin/cell adhesion, transforming growth factor (TGF)-beta and Notch regulate the endocytic system, and identified new genes involved in cargo sorting to a subset of signalling endosomes. A systems analysis by Bayesian networks further showed that the number, size, concentration of cargo and intracellular position of endosomes are not determined randomly but are subject to specific regulation, thus uncovering novel properties of the endocytic system.

Impact of leading presenting symptoms on the diagnostic performance of high-sensitivity cardiac troponin T and on outcomes in patients with suspected acute coronary syndrome.

BACKGROUND: Diagnostic performance of high-sensitivity cardiac troponin T (hs-cTnT) varies depending on presenting symptoms in patients with suspected acute coronary syndrome (ACS). METHODS: We compared performance measures of hs-cTnT among patients admitted to the emergency department with typical chest pain (angina), dyspnea, and atypical symptoms and assessed outcomes by leading presenting symptoms. RESULTS: A total of 658 patients suspected of ACS and presenting with typical chest pain (n = 241, 36.6%), dyspnea (n = 142, 21.6%), or atypical symptoms (n = 275, 41.8%) were included. Diagnostic accuracy of hs-cTnT on admission was higher among patients with typical chest pain compared to those with atypical symptoms [area under the curve (AUC) 0.823 vs AUC 0.776 vs AUC 0.705, P > 0.05 and P = 0.04]. Absolute concentration changes within 6 h improved accuracy among all subgroups, with the smallest added benefit in typical chest pain and dyspnea (ΔAUC, 0.078; P = 0.02 and 0.05, P > 0.05). During 1-year follow-up, dyspnea was associated with a higher risk of death (hazard ratio, 2.36; 95% CI, 1.26-4.43, P = 0.008) and death/AMI (hazard ratio, 2.23; 95% CI, 1.21-4.11, P = 0.01) compared to typical chest pain. Optimal discriminating values for hs-cTnT were higher among patients presenting with dyspnea compared to those with typical chest pain (91.2 vs 14.1 ng/L, P < 0.001). CONCLUSION: The diagnostic performance of hs-cTnT in patients with suspected ACS depends on the leading presenting symptom. Patients admitted with dyspnea represent a high-risk cohort in which the diagnosis of ACS is less frequent and with inferior performance of serial hs-cTnT measurements. Higher hs-cTnT cutoffs at baseline and absolute changes after 6 h help to identify non-STEMI (ST segment elevation myocardial infarction) in this population.

A 16-channel MR coil for simultaneous PET/MR imaging in breast cancer.

OBJECTIVES: To implement and evaluate a dedicated receiver array coil for simultaneous positron emission tomography/magnetic resonance (PET/MR) imaging in breast cancer. METHODS: A 16-channel receiver coil design was optimized for simultaneous PET/MR imaging. To assess MR performance, the signal-to-noise ratio, parallel imaging capability and image quality was evaluated in phantoms, volunteers and patients and compared to clinical standard protocols. For PET evaluation, quantitative (18) F-FDG PET images of phantoms and seven patients (14 lesions) were compared to images without the coil. In PET image reconstruction, a CT-based template of the coil was combined with the MR-acquired attenuation correction (AC) map of the phantom/patient. RESULTS: MR image quality was comparable to clinical MR-only examinations. PET evaluation in phantoms showed regionally varying underestimation of the standardised uptake value (SUV; mean 22 %) due to attenuation caused by the coil. This was improved by implementing the CT-based coil template in the AC (<2 % SUV underestimation). Patient data indicated that including the coil in the AC increased the SUV values in the lesions (21 ± 9 %). CONCLUSIONS: Using a dedicated PET/MR breast coil, state-of-the-art MRI was possible. In PET, accurate quantification and image homogeneity could be achieved if a CT-template of this coil was included in the AC for PET image reconstruction. KEY POINTS: • State-of-the-art breast MRI using a dedicated PET/MR breast coil is feasible. • A multi-channel design facilitates shorter MR acquisition times via parallel imaging. • An MR coil inside a simultaneous PET/MR system causes PET photon attenuation. • Including a coil CT-template in PET image reconstruction results in recovering accurate quantification.