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Introduction: Current management of metastatic colorectal cancer is based on neoadjuvant chemotherapy. Few studies have reported on surgery procedures in patients with metastatic colorectal cancer. The objective of this study was to describe our institutional experience with emergency surgery performed in patients with metastatic colorectal cancer during chemotherapy., Patients and Methods: This was a retrospective cohort study including adult patients of ≤80 years with a metastatic colorectal cancer between 2017 and 2020 and undergoing surgery during chemotherapy. Statistical analyses were based on Kaplan-Meier's curve and Cox proportional hazard model. The surgery statistical risk during chemotherapy was studied through all tumor and patient's characteristics. Multivariable logistic regression models were used to identify predictive factors of emergency surgery in these patients., Results: Seventy-two cases were identified and 60% patients undergone an emergency surgery. By Kaplan-Meier's analyses, intestinal surgery was much more frequent and early in patients who have severe stenosis (either blocking or only permeable using a gastroscope) at the time of diagnosis. Patients with severe malignant stenosis presented a 6.28 time higher surgery risk ( p  < .0001). The median time between admission and surgery was 54 days in patients with severe stenosis who were operated., Conclusion: The degree of colorectal tumor stenosis measured by endoscopy was a risk factor for emergency surgery in patients with metastatic colorectal cancer during neoadjuvant chemotherapy. In this group of patients presenting low survival outcomes, further studies are needed to define the place of preventive surgery, avoiding emergency surgery and morbidity in such fragile patients.

Background: Diagnostic accuracy of endomyocardial biopsy could improve if clinically safe magnetic resonance (MR)-compatible bioptomes were available. We explored two novel MR-compatible cardiac bioptomes for performance, safety, and clinical viability, employing in vivo minipig trials and phase-contrast synchrotron radiation computed microtomography (SRµCT)., Methods: Analysis of ex vivo obtained pig endomyocardial biopsies was performed using phase-contrast SRµCT and conventional two-dimensional histology. The technical performance was evaluated by measuring volume, inner and outer integrities, compression, and histological diagnostic value in 3 sets (6 per set) of biopsies for each experimental bioptome. The bioptomes were tested in vivo in 3 healthy minipigs per bioptome. The clinical feasibility was evaluated by procedural and cutting success as well as histological diagnostic value., Results: The bioptome with the 'grind-grind' design achieved similar values to control in compression (p = 0.822), inner (p = 0.628), and outer (p = 0.507), integrities ex vivo. It showed a better performance in the in vivo real-time MRI setting demonstrating a higher cutting success (91.7%) than the 'grind-anvil' (86.2%) design. In both ex vivo and in vivo evaluations, the 'grind-grind' design displayed sufficient diagnostic value (83% and 95%). The 'grind-anvil' design showed adequate diagnostic value both ex vivo and in vivo (78% and 87.5%) but was not comparable to control according to the three-dimensional (3D) analysis., Conclusion: A novel MR-compatible bioptome was identified as plausible in a clinical setting. Additionally, SRµCT and subsequent 3D structural analysis could be valuable in the label-free investigation of myocardial tissue at a micrometer level., Relevance Statement: Implementation of MR-guided biopsy can improve animal studies on structural myocardial changes at any point in an experimental setup. With further improvements in guiding catheters, MR-guided biopsy, using the new bioptome, has a potential to increase quality and diagnostic accuracy in patients both with structural and inflammatory cardiomyopathies., Key Points: • Novel MR-compatible bioptomes show promise for a clinical application. • SRµCT enabled detailed analysis of endomyocardial biopsies. • The bioptomes showed adequate in vivo performance without major complications., (© 2023. The Author(s).)

Chromatin has been shown to undergo diffusional motion, which is affected during gene transcription by RNA polymerase activity. However, the relationship between chromatin mobility and other genomic processes remains unclear. Hence, we set out to label the DNA directly in a sequence unbiased manner and followed labeled chromatin dynamics in interphase human cells expressing GFP-tagged proliferating cell nuclear antigen (PCNA), a cell cycle marker and core component of the DNA replication machinery. We detected decreased chromatin mobility during the S-phase compared to G1 and G2 phases in tumor as well as normal diploid cells using automated particle tracking. To gain insight into the dynamical organization of the genome during DNA replication, we determined labeled chromatin domain sizes and analyzed their motion in replicating cells. By correlating chromatin mobility proximal to the active sites of DNA synthesis, we showed that chromatin motion was locally constrained at the sites of DNA replication. Furthermore, inhibiting DNA synthesis led to increased loading of DNA polymerases. This was accompanied by accumulation of the single-stranded DNA binding protein on the chromatin and activation of DNA helicases further restricting local chromatin motion. We, therefore, propose that it is the loading of replisomes but not their catalytic activity that reduces the dynamics of replicating chromatin segments in the S-phase as well as their accessibility and probability of interactions with other genomic regions., Competing Interests: MP, CR, VC, JM, KC, JS, DL, KK, PP, AS, HL, KR, MC No competing interests declared, (© 2023, Pabba, Ritter, Chagin et al.)

The grip force dynamics during grasping and lifting of diversely weighted objects are highly informative about an individual's level of sensorimotor control and potential neurological condition. Therefore, grip force profiles might be used for assessment and bio-feedback training during neurorehabilitation therapy. Modern neurorehabilitation methods, such as exoskeleton-assisted grasping and virtual-reality-based hand function training, strongly differ from classical grasp-and-lift experiments which might influence the sensorimotor control of grasping and thus the characteristics of grip force profiles. In this feasibility study with six healthy participants, we investigated the changes in grip force profiles during exoskeleton-assisted grasping and grasping of virtual objects. Our results show that a light-weight and highly compliant hand exoskeleton is able to assist users during grasping while not removing the core characteristics of their grip force dynamics. Furthermore, we show that when participants grasp objects with virtual weights, they adapt quickly to unknown virtual weights and choose efficient grip forces. Moreover, predictive overshoot forces are produced that match inertial forces which would originate from a physical object of the same weight. In summary, these results suggest that users of advanced neurorehabilitation methods employ and adapt their prior internal forward models for sensorimotor control of grasping. Incorporating such insights about the grip force dynamics of human grasping in the design of neurorehabilitation methods, such as hand exoskeletons, might improve their usability and rehabilitative function.

Liver-generated plasma Apolipoprotein E (ApoE)-containing lipoproteins (LPs) (ApoE-LPs) play central roles in lipid transport and metabolism. Perturbations of ApoE can result in several metabolic disorders and ApoE genotypes have been associated with multiple diseases. ApoE is synthesized at the endoplasmic reticulum and transported to the Golgi apparatus for LP assembly; however, the ApoE-LPs transport pathway from there to the plasma membrane is largely unknown. Here, we established an integrative imaging approach based on a fully functional fluorescently tagged ApoE. We found that newly synthesized ApoE-LPs accumulate in CD63-positive endosomes of hepatocytes. In addition, we observed the co-egress of ApoE-LPs and CD63-positive intraluminal vesicles (ILVs), which are precursors of extracellular vesicles (EVs), along the late endosomal trafficking route in a microtubule-dependent manner. A fraction of ApoE-LPs associated with CD63-positive EVs appears to be co-transmitted from cell to cell. Given the important role of ApoE in viral infections, we employed as well-studied model the hepatitis C virus (HCV) and found that the viral replicase component nonstructural protein 5A (NS5A) is enriched in ApoE-containing ILVs. Interaction between NS5A and ApoE is required for the efficient release of ILVs containing HCV RNA. These vesicles are transported along the endosomal ApoE egress pathway. Taken together, our data argue for endosomal egress and transmission of hepatic ApoE-LPs, a pathway that is hijacked by HCV. Given the more general role of EV-mediated cell-to-cell communication, these insights provide new starting points for research into the pathophysiology of ApoE-related metabolic and infection-related disorders., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Pham 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: Structured reporting allows a high grade of standardization and thus a safe and unequivocal report communication. In the past years, the radiological societies have started several initiatives to base radiological reports on structured reporting rather than free text reporting., Methods: Upon invitation of the working group for Cardiovascular Imaging of the German Society of Radiology, in 2018 an interdisciplinary group of Radiologists, Cardiologists, Pediatric Cardiologists and Cardiothoracic surgeons -all experts on the field of cardiovascular MR and CT imaging- met for interdisciplinary consensus meetings at the University Hospital Cologne. The aim of these meetings was to develop and consent templates for structured reporting in cardiac MR and CT of various cardiovascular diseases., Results: Two templates for structured reporting of CMR in ischemia imaging and vitality imaging and two templates for structured reporting of CT imaging for planning Transcatheter Aortic Valve Implantation (TAVI; pre-TAVI-CT) and coronary CT were discussed, consented and transferred to a HTML 5/IHR MRRT compatible format. The templates were made available for free use on the website www.befundung.drg.de., Conclusion: This paper suggests consented templates in German language for the structured reporting of cross-sectional CMR imaging of ischemia and vitality as well as reporting of CT imaging pre-TAVI and coronary CT. The implementation of these templates is aimed at providing a constant level of high reporting quality and increasing the efficiency of report generation as well as a clinically based communication of imaging results., Key Points: · Structured reporting offers a constant level of high reporting quality and increases the efficiency of report generation as well as a clinically based communication of imaging results.. · For the first time templates in German language for the structured reporting of CMR imaging of ischemia and vitality and CT imaging pre-TAVI and coronary CT are reported.. · These templates will be made available on the website www.befundung.drg.de and can be commented via strukturierte-befundung@drg.de.., Zitierweise: · Soschynski M, Bunck AC, Beer M et al. Structured Reporting in Cross-Sectional Imaging of the Heart: Reporting Templates for CMR Imaging of Ischemia and Myocardial Viability and for Cardiac CT Imaging of Coronary Heart Disease and TAVI Planning. Fortschr Röntgenstr 2023; 195: 293 - 296., Competing Interests: The authors declare that they have no conflict of interest., (Thieme. All rights reserved.)

Objectives: There is an ongoing discussion on the optimal right to left (RV/LV) diameter ratio threshold and the best definition of RV dysfunction on computed tomography pulmonary angiography (CTPA) for risk assessment of pulmonary embolism (PE)., Methods: On routine diagnostic CTPA, volumetric and diameter measurements (axial and reconstructed views) of the ventricles and reflux of contrast medium into the inferior vena cava (IVC) and hepatic veins were assessed in consecutive PE patients enrolled in a prospective single-center registry. In-hospital adverse outcome was defined as PE-related death, cardiopulmonary resuscitation, mechanical ventilation or catecholamine administration., Results: Of 609 patients (median age, 69 [IQR, 56-77] years; 47 % male) included in the analysis, 68 patients (11.2 %) had an adverse outcome and 35 (5.7 %) died. While neither a RV/LV volume ratio ≥1.0 nor RV/LV diameter ratios ≥1.0 were able to predict an adverse outcome, higher thresholds increased specificity. Further, neither volumetric measurements nor reconstruction of images provided superior prognostic information compared to RV/LV ratios measured in axial planes. The combination of an axial RV/LV diameter ratio ≥1.5 with substantial reflux of contrast medium was present in 134 patients (22 %) and associated with the best prognostic performance to predict an adverse outcome in unselected (OR 3.7 [95 % CI, 2.0-6.6]) and normotensive (OR 2.8 [95 % CI, 1.1-6.7]) patients., Conclusion: A new definition of RV dysfunction (axial RV/LV diameter ratio ≥1.5 and substantial reflux of contrast medium to the IVC and hepatic veins) allows an optimized CTPA-based prediction of PE-related adverse outcome., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Aims: Physical activity (PA) is a mainstay of cardiovascular prevention. This study aimed to identify metabolic mediators of PA that protect against the development of atherosclerosis., Methods and Results: A total of 2160 participants in the LIFE heart study were analysed with data on PA and vascular phenotyping. In a targeted metabolomic approach, 61 metabolites (amino acids and acylcarnitines) were measured using liquid chromatography-tandem mass spectrometry. We investigated the interactions between PA, metabolites and markers of atherosclerosis in order to uncover possible mediation effects. Intended sports activity, but no daily PA, was associated with a lower degree of atherosclerosis, odds ratio (OR) for total atherosclerotic burden of 0.76 (95% confidence interval 0.62-0.94), carotid artery plaque OR 0.79 (0.66-0.96), and peripheral artery disease OR 0.74 (0.56-0.98). Twelve amino acids, free carnitine, five acylcarnitines were associated with sports activity. Of these, eight metabolites were also associated with the degree of atherosclerosis. In the mediation analyses, a cluster of amino acids (arginine, glutamine, pipecolic acid, taurine) were considered as possible mediators of atheroprotection. In contrast, a group of members of the carnitine metabolism (free carnitine, acetyl carnitine, octadecenoyl carnitine) were associated with inactivity and higher atherosclerotic burden., Conclusion: Our metabolomic approach, which is integrated into a mediation model, provides transformative insights into the complex metabolic processes involved in atheroprotection. Metabolites with antioxidant and endothelial active properties are believed to be possible mediators of atheroprotection. The metabolomic mediation approach can support the understanding of complex diseases in order to identify targets for prevention and therapy., (© The Author(s) 2020. Published by Oxford University Press on behalf of the European Society of Cardiology.)

Background: Percutaneous treatment of secondary thoracic and abdominal retention formations after blunt or penetrating trauma now represents a standard interventional radiological procedure. Various supportive imaging procedures are available, whereby computed tomography is mostly the treatment of choice due to the high diagnostic sensitivity., Objective: Based on clinical examples this review article gives an overview of the state of the art minimally invasive interventional treatment of secondary posttraumatic retention formations of the thorax and abdomen. The indications and contraindications are illustrated and typical techniques and access routes are described., Material and Methods: Besides the general introduction and technical part, the article is divided into the anatomical compartments thorax and abdomen and frequently asked questions are dealt with., Conclusion: After the study of this article you should have got to know and understand the indications for a minimally invasive approach, the possible techniques and necessary materials as well as the indications and contraindications., (© 2021. Springer Medizin Verlag GmbH, ein Teil von Springer Nature.)

The Rapid Risk of Violence Screen (RROVS) is a brief screening tool that is designed for use in community-based behavioral health service settings to identify people who may need comprehensive violence risk assessment. This study examined the association between the RROVS total score and future criminal justice involvement including violent offenses. Results from this study suggest that the RROVS screening tool has predictive validity as it is associated with later criminal justice involvement with a violent offense. The RROVS may be a helpful tool for community-based behavioral health providers to screen incoming clients for violence risk to inform whether additional assessment for violence potential is warranted., (© 2020. National Council for Behavioral Health.)

Aims: Right atrial (RA) dilation and stretch provide prognostic information in patients with cardiovascular diseases. We investigated the prevalence, confounding factors and prognostic relevance of RA dilation in patients with pulmonary embolism (PE)., Methods: Overall, 609 PE patients were consecutively included in a prospective single-centre registry between September 2008 and August 2017. Volumetric measurements of heart chambers were performed on routine non-electrocardiographic-gated computed tomography and plasma concentrations of mid-regional pro-atrial natriuretic peptide (MR-proANP) measured on admission. An in-hospital adverse outcome was defined as PE-related death, cardiopulmonary resuscitation, mechanical ventilation or catecholamine administration., Results: Patients with an adverse outcome (11.2%) had larger RA volumes (median 120 (interquartile range 84-152) versus 102 (78-134) mL; p=0.013), RA/left atrial (LA) volume ratios (1.7 (1.2-2.4) versus 1.3 (1.1-1.7); p<0.001) and MR-proANP levels (282 (157-481) versus 129 (64-238) pmol·L -1 ; p<0.001) compared to patients with a favourable outcome. Overall, 499 patients (81.9%) had a RA/LA volume ratio ≥1.0 and a calculated cut-off value of 1.8 (area under the curve 0.64, 95% CI 0.56-0.71) predicted an adverse outcome, both in unselected (OR 3.1, 95% CI 1.9-5.2) and normotensive patients (OR 2.7, 95% CI 1.3-5.6). MR-proANP ≥120 pmol·L -1 was identified as an independent predictor of an adverse outcome, both in unselected (OR 4.6, 95% CI 2.3-9.3) and normotensive patients (OR 5.1, 95% CI 1.5-17.6)., Conclusions: RA dilation is a frequent finding in patients with PE. However, the prognostic performance of RA dilation appears inferior compared to established risk stratification markers. MR-proANP predicted an in-hospital adverse outcome, both in unselected and normotensive PE patients, integrating different prognostic relevant information from comorbidities., Competing Interests: Conflict of interest: M.H. Lerchbaumer reports having received consultancy honoraria from Siemens Healthineers. Conflict of interest: M. Ebner has nothing to disclose. Conflict of interest: C.O. Ritter has nothing to disclose. Conflict of interest: L. Steimke has nothing to disclose. Conflict of interest: N.I.J. Rogge has nothing to disclose. Conflict of interest: C. Sentler has nothing to disclose. Conflict of interest: A. Thielmann has nothing to disclose. Conflict of interest: L. Hobohm reports personal fees from MSD and Actelion outside the submitted work. Conflict of interest: K. Keller has nothing to disclose. Conflict of interest: J. Lotz has nothing to disclose. Conflict of interest: G. Hasenfuß reports personal fees from Corvia, Servier, Impulse Dynamics, Novartis, AstraZeneca, Vifor Pharma, Berlin Chemie and Springer outside the submitted work. Conflict of interest: R. Wachter reports grants from Boehringer Ingelheim during the conduct of the study; personal fees and other support from Bayer, Berlin Chemie and Boehringer Ingelheim, other support from Boston Scientific, personal fees from Bristol-Myers-Squibb, personal fees and other support from CVRx, other support from Gilead and Johnson & Johnson, personal fees and other support from Medtronic and Novartis, personal fees from Pfizer, other support from Relypsa, personal fees from Sanofi, and personal fees and other support from Servier, outside the submitted work. Conflict of interest: B. Hamm reports personal fees from Canon Medical Imaging outside the submitted work. Conflict of interest: S.V. Konstantinides reports grants from the German Federal Ministry of Education and Research (BMBF 01EO1003 and BMBF 01EO1503) during the conduct of the study; grants and personal fees from Bayer, grants and personal fees from Boehringer Ingelheim, grants and personal fees from Daiichi-Sankyo, personal fees from MSD, grants and personal fees from Pfizer–Bristol-Myers-Squibb, and grants and personal fees from Actelion, outside the submitted work. Conflict of interest: G. Aviram reports grants from Philips Medical Systems outside the submitted work. Conflict of interest: M. Lankeit reports grants from the German Federal Ministry of Education and Research (BMBF 01EO1003 and 01EO1503), and BRAHMS–Thermo Fisher Scientific, during the conduct of the study; and personal fees and nonfinancial support from Actelion, Bayer, Daiichi-Sankyo, MSD and Pfizer–Bristol-Myers-Squibb, and grants and personal fees from BRAHMS–Thermo Fisher Scientific, outside the submitted work., (Copyright ©ERS 2021.)

Background: The effect of smoking on coronary vasomotion has been investigated in the past with various imaging techniques in both short- and long-term smokers. Additionally, coronary vasomotion has been shown to be normalized in long-term smokers by L-Arginine acting as a substrate for NO synthase, revealing the coronary endothelium as the major site of abnormal vasomotor response. Aim of the prospective cohort study was to investigate coronary vasomotion of young healthy short-term smokers via magnetic resonance cold pressor test with and without the administration of L-Arginine and compare obtained results with the ones from nonsmokers., Methods: Myocardial blood flow (MBF) was quantified with first-pass perfusion MRI on a 1.5 T scanner in healthy short-term smokers (N = 10, age: 25.0 ± 2.8 years, 5.0 ± 2.9 pack years) and nonsmokers (N = 10, age: 34.3 ± 13.6) both at rest and during cold pressor test (CPT). Smokers underwent an additional examination after administration of L-Arginine within a median of 7 days of the naïve examination., Results: MBF at rest turned out to be 0.77 ± 0.30 (smokers with no L-Arginine; mean ± standard deviation), 0.66 ± 0.21 (smokers L-Arginine) and 0.84 ± 0.08 (nonsmokers). Values under CPT were 1.21 ± 0.42 (smokers no L-Arginine), 1.09 ± 0.35 (smokers L-Arginine) and 1.63 ± 0.33 (nonsmokers). In all groups, MBF was significantly increased under CPT compared to the corresponding rest examination (p < 0.05 in all cases). Additionally, MBF under CPT was significantly different between the smokers and the nonsmokers (p = 0.002). MBF at rest was significantly different between the smokers when L-Arginine was given and the nonsmokers (p = 0.035)., Conclusion: Short-term smokers showed a reduced response to cold both with and without the administration of L-Arginine. However, absolute MBF values under CPT were lower compared to nonsmokers independently of L-Arginine administration.

We use a perceptual control model of identity to examine the relationship between stigmatized appraisals (from self and other) and well-being among individuals with serious mental illness. We also examine the role of stigma resistance strategies in the identity process. Using in-depth interviews with active clients of a community mental health center (N = 156), we find that deflection, or distancing oneself from mental illness, is associated with greater self-esteem and fewer depressive symptoms. Challenging others through education is associated with higher self-esteem, and challenging stigma through activism is associated with fewer depressive symptoms. Activism also moderates the relationship between identity discrepancy (the difference between appraisals from self and other) and well-being; however, the extent to which activism is helpful or harmful depends on whether appraisals from others are more or less stigmatizing than self-views. We discuss the implications of these findings for identity and stigma research.

The purpose of this exploratory study is to: (1) assess prevalence of childhood adversities and posttraumatic stress disorder (PTSD); (2) assess their association, and; (3) explore whether proximal sources of stress affect this relationship and/or have an association with PTSD among people with severe and persistent psychological disorders. Using data from 141 respondents, we assess the extent to which individuals in this population experienced 17 PTSD symptoms, various correlates to probable PTSD, and the most relevant of these factors in a multivariate logistic regression. Overall, 27% of the participants met study criteria for probable PTSD and each symptom was reported by at least 18% of the sample. Multivariate logistic regression models indicated that interpersonal conflict and being a victim of a crime were significantly related to probable PTSD. We discuss these findings in relation to treatment and course of disease for people suffering from severe and persistent mental illness experiencing a traumatic event.

The first molecular compound with all five pnictogens was obtained by a multi-step reaction. Lithiation of the (bisamido)diazadiarsetidine (tBuNAs) 2 (tBuNH) 2 in aliphatic solvents leads to the dimeric metallated species [(tBuNAs) 2 (tBuNLi) 2 ] 2 (1 2 ). Upon reactions with AsCl 3 , SbCl 3 and BiCl 3 the polycyclic compounds [(tBuNAs) 2 (tBuN) 2 ]PnCl (Pn=As (2), Sb (3), Bi (4)) can be obtained. Conversion of 2-4 with [tBu 2 SbP(tBu)Li(OEt 2 )] 2 leads to the remarkable interpnictogens [(tBuNAs) 2 (tBuN) 2 ]PnP(tBu)SbtBu 2 (Pn=As (5), Sb (6), Bi (7)), whereby 7 is the first example of a molecule containing all five Group 15 elements. The compound with adjacent AsNBiPSb-chains is surprisingly stable and does not show high sensibility against light as the labile Bi-P bond might suggest., (© 2020 The Authors. Published by Wiley-VCH Verlag GmbH & Co. KGaA.)

Background: Bone marrow stem cell clonal dysfunction by somatic mutation is suspected to affect post-infarction myocardial regeneration after coronary bypass surgery (CABG)., Methods: Transcriptome and variant expression analysis was studied in the phase 3 PERFECT trial post myocardial infarction CABG and CD133 + bone marrow derived hematopoetic stem cells showing difference in left ventricular ejection fraction (∆LVEF) myocardial regeneration Responders (n=14; ∆LVEF +16% day 180/0) and Non-responders (n=9; ∆LVEF -1.1% day 180/0). Subsequently, the findings have been validated in an independent patient cohort (n=14) as well as in two preclinical mouse models investigating SH2B3/LNK antisense or knockout deficient conditions., Findings: 1. Clinical: R differed from NR in a total of 161 genes in differential expression (n=23, q<0•05) and 872 genes in coexpression analysis (n=23, q<0•05). Machine Learning clustering analysis revealed distinct RvsNR preoperative gene-expression signatures in peripheral blood acorrelated to SH2B3 (p<0.05). Mutation analysis revealed increased specific variants in RvsNR. (R: 48 genes; NR: 224 genes). 2. Preclinical:SH2B3/LNK-silenced hematopoietic stem cell (HSC) clones displayed significant overgrowth of myeloid and immune cells in bone marrow, peripheral blood, and tissue at day 160 after competitive bone-marrow transplantation into mice. SH2B3/LNK -/- mice demonstrated enhanced cardiac repair through augmenting the kinetics of bone marrow-derived endothelial progenitor cells, increased capillary density in ischemic myocardium, and reduced left ventricular fibrosis with preserved cardiac function. 3., Validation: Evaluation analysis in 14 additional patients revealed 85% RvsNR (12/14 patients) prediction accuracy for the identified biomarker signature., Interpretation: Myocardial repair is affected by HSC gene response and somatic mutation. Machine Learning can be utilized to identify and predict pathological HSC response., Funding: German Ministry of Research and Education (BMBF): Reference and Translation Center for Cardiac Stem Cell Therapy - FKZ0312138A and FKZ031L0106C, German Ministry of Research and Education (BMBF): Collaborative research center - DFG:SFB738 and Center of Excellence - DFG:EC-REBIRTH), European Social Fonds: ESF/IV-WM-B34-0011/08, ESF/IV-WM-B34-0030/10, and Miltenyi Biotec GmbH, Bergisch-Gladbach, Germany. Japanese Ministry of Health : Health and Labour Sciences Research Grant (H14-trans-001, H17-trans-002) TRIAL REGISTRATION: ClinicalTrials.gov NCT00950274., (Copyright © 2020 The Author(s). Published by Elsevier B.V. All rights reserved.)

Competing Interests: Die Autoren geben an, dass kein Interessenkonflikt besteht.

Backround:  Structured reports have numerous benefits through standardizing the way imaging findings are reported and communicated. Nevertheless, the adoption of structured reports in everyday radiological practice is still limited. In view of the irrefutable benefits, various national and international radiological societies have started initiatives which aim at promoting a broader use of structured reports. Up to now, no consented templates in German language existed for the reporting of cross-sectional imaging studies of the heart., Method:  Upon invitation of the working group for Cardiovascular Imaging of the German Society of Radiology a panel of radiologists, cardiologists, pediatric cardiologists and cardiothoracic surgeons, experts on the field of cardiovascular imaging and structured reporting, met for two interdisciplinary consensus meetings at the University Hospital Cologne in 2018. The aim of these meetings was to develop and agree on templates for the reporting of MR and CT studies of various cardiovascular disease entities., Results:  During the meetings the panel of experts developed and reached consensus on 11 different templates for the structured reporting of the following: myocarditis, dilated cardiomyopathy, hypertrophic (obstructive) cardiomyopathy, arrythmogenic right ventricular cardiomyopathy, siderosis, ischemia and vitality imaging, tetralogy of Fallot, aortic coarctation, coronary CT and CT for Transcatheter Aortic Valve Implantation (TAVI) planning. The first five templates are presented in this publication and are currently being transferred to a HTML 5/IHR MRRT compatible format. Subsequently, the templates will be made available for free use on the website www.befundung.drg.de., Conclusion:  For the first time, consented templates in German language for the structured reporting of cross-sectional imaging studies of the heart are presented. These templates are aimed at providing a constant level of high reporting quality and increasing the efficiency of the generation and communication of imaging reports., Key Points:   · Structured reporting offers numerous benefits by standardizing generation and communication of imaging reports.. · For the first time templates in German language for the structured reporting of CMR imaging studies of cardiomyopathies are presented. · These templates will be made available on the website www.befundung.drg.de and can be commented via agit-sr@googlegroups.com.., Citation Format: · Bunck AC, Baeßler B, Ritter C et al. Structured Reporting in Cross-Sectional Imaging of the Heart: Reporting Templates for CMR Imaging of Cardiomyopathies (Myocarditis, Dilated Cardiomyopathy, Hypertrophic Cardiomyopathy, Arrhythmogenic Right Ventricular cardiomyopathy and Siderosis). Fortschr Röntgenstr 2020; 192: 27 - 37., Competing Interests: The authors declare that they have no conflict of interest., (© Georg Thieme Verlag KG Stuttgart · New York.)

Purpose: Automated analysis of microscopy image data typically requires complex pipelines that involve multiple methods for different image analysis tasks. To achieve best results of the analysis pipelines, method-dependent hyperparameters need to be optimized. However, complex pipelines often suffer from the fact that calculation of the gradient of the loss function is analytically or computationally infeasible. Therefore, first- or higher-order optimization methods cannot be applied., Methods: We developed a new framework for zero-order black-box hyperparameter optimization called HyperHyper, which has a modular architecture that separates hyperparameter sampling and optimization. We also developed a visualization of the loss function based on infimum projection to obtain further insights into the optimization problem., Results: We applied HyperHyper in three different experiments with different imaging modalities, and evaluated in total more than 400.000 hyperparameter combinations. HyperHyper was used for optimizing two pipelines for cell nuclei segmentation in prostate tissue microscopy images and two pipelines for detection of hepatitis C virus proteins in live cell microscopy data. We evaluated the impact of separating the sampling and optimization strategy using different optimizers and employed an infimum projection for visualizing the hyperparameter space., Conclusions: The separation of sampling and optimization strategy of the proposed HyperHyper optimization framework improves the result of the investigated image analysis pipelines. Visualization of the loss function based on infimum projection enables gaining further insights on the optimization process.

Objective: This study examined hospitalizations for individuals receiving assisted outpatient treatment (AOT), some of whom also received assertive community treatment (ACT). We examined whether participation in AOT, as well as in AOT paired with ACT services, was associated with reduced hospitalizations., Methods: Data were collected for 74 people who were receiving AOT for at least 6 months. Comparisons were made between those receiving AOT with ACT and those receiving AOT without ACT. Changes were examined in number and days of hospitalization before, during, and after AOT on an annualized basis., Results: AOT was associated with reduced hospitalizations and hospital days during and after the court order. Participating in AOT without ACT was associated with fewer hospitalizations during and after AOT and fewer days hospitalized after the court order ended., Conclusions: Individuals whose needs can be met with less intensive services while under an AOT order may not require ACT.

The hepatitis C virus (HCV) is a major cause of chronic liver disease, affecting around 71 million people worldwide. Viral RNA replication occurs in a membranous compartment composed of double-membrane vesicles (DMVs), whereas virus particles are thought to form by budding into the endoplasmic reticulum (ER). It is unknown how these steps are orchestrated in space and time. Here, we established an imaging system to visualize HCV structural and replicase proteins in live cells and with high resolution. We determined the conditions for the recruitment of viral proteins to putative assembly sites and studied the dynamics of this event and the underlying ultrastructure. Most notable was the selective recruitment of ER membranes around lipid droplets where structural proteins and the viral replicase colocalize. Moreover, ER membranes wrapping lipid droplets were decorated with double membrane vesicles, providing a topological map of how HCV might coordinate the steps of viral replication and virion assembly., (Copyright © 2019 Department of Infectious Diseases, Molecular Virology, Heidelberg University. Published by Elsevier Inc. All rights reserved.)

Pathogens face varying microenvironments in vivo, but suitable experimental systems and analysis tools to dissect how three-dimensional (3D) tissue environments impact pathogen spread are lacking. Here we develop an Integrative method to Study Pathogen spread by Experiment and Computation within Tissue-like 3D cultures (INSPECT-3D), combining quantification of pathogen replication with imaging to study single-cell and cell population dynamics. We apply INSPECT-3D to analyze HIV-1 spread between primary human CD4 T-lymphocytes using collagen as tissue-like 3D-scaffold. Measurements of virus replication, infectivity, diffusion, cellular motility and interactions are combined by mathematical analyses into an integrated spatial infection model to estimate parameters governing HIV-1 spread. This reveals that environmental restrictions limit infection by cell-free virions but promote cell-associated HIV-1 transmission. Experimental validation identifies cell motility and density as essential determinants of efficacy and mode of HIV-1 spread in 3D. INSPECT-3D represents an adaptable method for quantitative time-resolved analyses of 3D pathogen spread.

Background: Cardiovascular magnetic resonance (CMR) represents the clinical gold standard for the assessment of biventricular morphology and function. Since manual post-processing is time-consuming and prone to observer variability, efforts have been directed towards automated volumetric quantification. In this study, we sought to validate the accuracy of a novel approach providing fully automated quantification of biventricular volumes and function in a "real-world" clinical setting., Methods: Three-hundred CMR examinations were randomly selected from the local data base. Fully automated quantification of left ventricular (LV) mass, LV and right ventricular (RV) end-diastolic and end-systolic volumes (EDV/ESV), stroke volume (SV) and ejection fraction (EF) were performed overnight using commercially available software (suiteHEART®, Neosoft, Pewaukee, Wisconsin, USA). Parameters were compared to manual assessments (QMass®, Medis Medical Imaging Systems, Leiden, Netherlands). Sub-group analyses were further performed according to image quality, scanner field strength, the presence of implanted aortic valves and repaired Tetralogy of Fallot (ToF)., Results: Biventricular automated segmentation was feasible in all 300 cases. Overall agreement between fully automated and manually derived LV parameters was good (LV-EF: intra-class correlation coefficient [ICC] 0.95; bias - 2.5% [SD 5.9%]), whilst RV agreement was lower (RV-EF: ICC 0.72; bias 5.8% [SD 9.6%]). Lowest agreement was observed in case of severely altered anatomy, e.g. marked RV dilation but normal LV dimensions in repaired ToF (LV parameters ICC 0.73-0.91; RV parameters ICC 0.41-0.94) and/or reduced image quality (LV parameters ICC 0.86-0.95; RV parameters ICC 0.56-0.91), which was more common on 3.0 T than on 1.5 T., Conclusions: Fully automated assessments of biventricular morphology and function is robust and accurate in a clinical routine setting with good image quality and can be performed without any user interaction. However, in case of demanding anatomy (e.g. repaired ToF, severe LV hypertrophy) or reduced image quality, quality check and manual re-contouring are still required.

Herein we present the synthesis and characterization of di-tertiary butyl substituted (pseudo-)halogen bismuthanes tBu2BiX (X = Cl (1), Br (2), I (3), CN (4), N3 (5), SCN (6)). These compounds were obtained via different reaction paths. Compound 1 was obtained by a Grignard reaction of BiCl3 with two equivalents of tBuMgCl, whereas compounds 2, 3, 4 and 6 were synthesised by a oxidative addition/reductive elimination pathway starting from tBu3Bi and X2 (X = Br, I, CN, SCN). Finally, azide 5 was obtained by the reaction of 1 and NaN3. Secondary bonding interactions in the solid state within all the investigated compounds (1-6) cause additional stabilisation. Starting from tBu2BiCl, the completely tbutyl substituted ternary interpnictogen compound tBu2Bi(tBuP)SbtBu2 (7) was synthesized through the reaction with [tBu2SbP(tBu)Li(Et2O)]2. All new compounds were characterized by means of X-ray diffraction and mass spectrometry as well as NMR and IR spectroscopy.

Background: In its course, diabetes impairs microvascular function through endothelial dysfunction. As the response of myocardial perfusion to sympathetic stimulation through cold is modulated by endothelium-related factors, an incipient endothelial dysfunction might be observed noninvasively by investigation of myocardial perfusion with a cold pressor test (CPT). This approach has been used in clinical MRI previously., Purpose: To assess endothelial function of patients suffering from type 1 diabetes by MR CPT., Study Type: Prospective cohort study., Subjects: Twenty type 1 diabetics and 20 healthy volunteers., Field Strength/sequence: 3T, dynamic contrast enhanced perfusion (steady-state free precession)., Assessment: Absolute quantitative myocardial perfusion values at rest and under CPT., Statistical Tests: Kolmogorov-Smirnov test to determine normal distribution of the results. T-test for independent samples., Results: Patients' mean myocardial perfusion was 0.68 cc/g/min at rest and 0.80 cc/g/min during CPT, respective values of 0.81 cc/g/min and 1.36 cc/g/min were found in healthy volunteers. Perfusion values differed significantly for CPT (P < 0.01) but not for resting conditions (P = 0.06)., Data Conclusion: This study demonstrated that endothelial function might be impaired in type 1 diabetes patients. This fosters the thesis that endothelial function may serve as an early biomarker for coronary artery disease in patients with type 1 diabetes while these patients are still clinically asymptomatic., Level of Evidence: 2 Technical Efficacy: Stage 3 J. Magn. Reson. Imaging 2018;48:1595-1601., (© 2018 International Society for Magnetic Resonance in Medicine.)

Introduction: The high burden of left ventricular (LV) abnormalities in patients with advanced chronic kidney disease (CKD) is well established. However, less is known about the prevalence, patterns, and determinants of LV abnormalities in patients with early CKD., Methods: We examined LV structure in 290 patients with a median estimated glomerular filtration rate (eGFR) of 51 ml/min per 1.73 m 2 by magnetic resonance imaging (MRI). We explored associations with clinical and hemodynamic parameters, hydration (bioimpedance), endothelial function, inflammation (including C-reactive protein and tumor necrosis factor-α and its soluble receptors) and mineral bone disease (MBD) markers (including vitamin D, parathyroid hormone, α-klotho and fibroblast growth factor-23)., Results: Normal geometry was found in 56% of patients, dilation in 4%, concentric remodeling in 10%, and LV hypertrophy in 29%. Linear regression analysis revealed that greater LV mass was independently associated with male sex, greater body mass index (BMI), and higher 24-hour systolic blood pressure (24-hour SBP). Concentric remodeling was independently associated with age, male sex, higher 24-hour SBP, and greater hemoglobin levels. Surprisingly, neither hydration status, nor endothelial function, nor any of the inflammatory or MBD parameters added significantly to these models., Conclusion: Abnormal LV structure was found in almost one-half of the patients. Reducing BMI and 24-hour SBP and avoiding high hemoglobin concentrations appear to be the key factors to prevent abnormal LV remodeling in patients with mild-to-moderate CKD.

In patients with chronic kidney disease, data on blood pressure (BP) pattern and its association with target organ damage, which indicates elevated cardiovascular risk, are sparse. In 305 treated hypertensive chronic kidney disease patients, we assessed BP pattern, left ventricular mass (magnetic resonance imaging), intima-media thickness (ultrasound), 24-hour-pulse wave velocity and 24-hour-central augmentation index (Mobil-O-Graph). Controlled hypertension (normal office and ambulatory BP) was found in 41% and sustained uncontrolled hypertension (elevated office and ambulatory BP) in 30% of patients. Misclassification of BP status occurred in 29%: white coat uncontrolled hypertension (elevated office but normal ambulatory BP) was detected in 11% and masked uncontrolled hypertension (normal office but elevated ambulatory BP) in 18% of patients. Left ventricular mass was increased in white coat uncontrolled hypertension (+11.2 g), masked uncontrolled hypertension (+9.4 g), and sustained uncontrolled hypertension (+16.6 g) compared with controlled hypertension. Intima-media thickness was similar across all 4 BP groups. Twenty-four hour-pulse wave velocity and 24-hour-central augmentation index were increased in masked uncontrolled hypertension (+0.5 m/sec and +2.5%) and sustained uncontrolled hypertension (+0.5 m/sec and +2.9%) compared with controlled hypertension. In conclusion, based on office BP measurements, misclassification of true BP status occurred in almost one-third of chronic kidney disease patients. Both types of misclassification (white coat uncontrolled hypertension and masked uncontrolled hypertension) were associated with parameters of target organ damage. Ambulatory BP monitoring should be used routinely to identify chronic kidney disease patients at high cardiovascular risk.

Objective: Mental health courts and assisted outpatient treatment (AOT) are tools to help people with serious mental illness engage in treatment and avoid or reduce institutionalization. As both programs become increasingly prevalent, questions remain about whether people with severe mental illness who receive AOT have the same characteristics, histories, and service needs as those who participate in mental health courts. If there are differences, each program may require assessments and interventions tailored to the specific characteristics and needs of participants., Methods: This study examined administrative criminal justice and mental health services data for 261 people with serious mental illness who participated in AOT, a mental health court, or both over seven years., Results: Three percent of the sample participated in both programs. Compared with participants in mental health court, participants in AOT were older, less likely to have an alcohol use disorder, and more likely to have a schizophrenia spectrum disorder than a bipolar disorder. The participants' histories of crisis mental health service utilization, hospitalization, and incarceration prior to program entry varied significantly by program., Conclusions: The findings suggest that there are differences among individuals with serious mental illness who are served by AOT and mental health court programs. AOT participants had greater engagement with mental health services, and a significant portion of AOT participants also had a prior criminal history that placed them at risk of future justice involvement. Program administrators need to recognize and address the clinical and criminogenic needs that place individuals at risk of becoming hospitalized and incarcerated.

Arrhythmogenic right ventricular cardiomyopathy (ARVC) is a potentially lethal disease that is well described in adults. In pediatric patients, however, identification of patients at risk of adverse events of ARVC remains a challenge. We aimed to determine which criteria of the revised Task Force Criteria (rTFC), alone or combined, have an impact on diagnosis of ARVC when compared to disease-specific genetic mutations in pediatric patients ≤ 18 years. Between September 2010 and December 2013, 48 consecutive young patients ≤ 18 years of age (mean 14, range of 12.9-15.1 years) underwent contrast-enhanced magnetic resonance imaging (CMR), genetic testing, and comprehensive clinical work-up for ARVC criteria to test for clinically suspected ARVC. As specified by the rTFC, patients were grouped into four categories: "definite," "borderline," "possible," and "none" ARVC. Of the 48 patients, 12 were found to have gene mutations of either the desmoplakin (9/12) or plakophilin (3/12) locus. According to rTFC 12/48 patients were considered as "definite" ARVC (25%), while 10/12 (83.3%) had an ARVC-specific gene mutation. Of the remaining 36 patients, 6 (12.5%) were grouped as "borderline" ARVC, 7 (14.6%) as "possible" ARVC (including the remaining two genetic mutations), and 22 (45.8%) as "none" ARVC, respectively. Statistical analysis of ARVC criteria in patients diagnosed with "definite" ARVC revealed high prevalence of positive findings by imaging (CMR and echocardiography) and positive genetics. The positive predictive value to detect "definite" ARVC by genotyping was 83.3%, while the negative predictive value was 94%. Logistic regression analyses for different criteria combinations revealed that imaging modalities (echo and CMR combined) and abnormalities of 12-lead ECG were significant markers (p < 0.01). Positive results of endomyocardial biopsies or arrhythmia on ECG or Holter as defined by the rTFC were not significant in this analysis. The rTFC for ARVC should be used with caution in children and adolescents suspected for ARVC. 12-Lead ECG and imaging modalities (CMR and echo) were of major value, positive results should prompt genetic testing.

Purpose: We aimed to quantify atrial and ventricular myocardial deformation in Ebstein's Anomaly (EA) in a case-control study with cardiovascular magnetic resonance (CMR) feature tracking and to correlate changes in cardiac performance with the severity of disease and clinical heart failure parameters., Materials and Methods: Atrial and ventricular deformation was measured using CMR feature tracking in 30 EA and 20 healthy control subjects. Atrial performance was characterized using longitudinal strain and strain rate parameters for reservoir function, conduit function and booster pump function. Ventricular performance was characterized using RV and LV global longitudinal strain (εl) and LV circumferential and radial strain (εc and εr). Volumetric measurements for the ventricles including the Total Right/Left-Volume-Index (R/L-Volume-Index) and heart failure markers (BNP, NYHA class) were also quantified., Results: EA patients showed significantly impaired right atrial performance, which correlated with heart failure markers (NYHA, BNP, R/L-Volume-Index). LA function in EA patients was also impaired with atrial contractile function correlating with NYHA class. EA patients exhibited impaired RV myocardial deformation, also with a significant correlation with heart failure markers., Conclusion: CMR feature tracking can be used to quantify ventricular and atrial function in a complex cardiac malformation such as EA. EA is characterized by impaired quantitative right heart atrio-ventricular deformation, which is associated with heart failure severity. While LV function remains preserved, there is also significant impairment of LA function. These quantitative performance parameters may represent early markers of cardiac deterioration of potential value in the clinical management of EA., (Copyright © 2017 The Authors. Published by Elsevier B.V. All rights reserved.)

Objectives: Magnetic resonance imaging (MRI) is regarded as a non-harming and non-invasive imaging modality with high tissue contrast and almost no side effects. Compared to other cross-sectional imaging modalities, MRI does not use ionising radiation. Recently, however, strong magnetic fields as applied in clinical MRI scanners have been suspected to induce DNA double-strand breaks in human lymphocytes., Methods: In this study we investigated the impact of 3-T cardiac MRI examinations on the induction of DNA double-strand breaks in peripheral mononuclear cells by γH2AX staining and flow cytometry analysis. The study cohort consisted of 73 healthy non-smoking volunteers with 36 volunteers undergoing CMRI and 37 controls without intervention. Differences between the two cohorts were analysed by a mixed linear model with repeated measures., Results: Both cohorts showed a significant increase in the γH2AX signal from baseline to post-procedure of 6.7 % (SD 7.18 %) and 7.8 % (SD 6.61 %), respectively. However, the difference between the two groups was not significant., Conclusion: Based on our study, γH2AX flow cytometry shows no evidence that 3-T MRI examinations as used in cardiac scans impair DNA integrity in peripheral mononuclear cells., Key Points: • No evidence for DNA double-strand breaks after cardiac MRI. • Prospective study underlines safe use of MRI with regard to DNA damage. • Controlled trial involving both genders investigating DNA DSBs after 3-T MRI.

Left atrial (LA) enlargement and dysfunction are markers of chronic diastolic dysfunction and an important predictor of adverse cardiovascular and cerebrovascular outcomes. Accordingly, accurate quantification of left atrial volume (LAV) and function is needed. In routine clinical cardiovascular magnetic resonance (CMR) imaging the biplane area-length method (Bi-ALM) is frequently applied due to time-saving image acquisition and analysis. However, given the varying anatomy of the LA we hypothesized that the diagnostic accuracy of the Bi-ALM is not sufficient and that results would be different from a precise volumetric assessment of transversal multi-slice cine images using Simpson's method. Thirty one patients of the FIND-AF RANDOMISED -study with status post acute cerebral ischemia (mean age 70.5 ± 6.2 years) received CMR imaging at 3T. The study protocol included cine SSFP sequences in standard 2- and 4 CV and a stack of contiguous slices in transversal orientation. Total, passive and active LA emptying fractions were calculated from LA maximal volume, minimal volume and volume prior to atrial contraction. Intra- and inter-observer variability was assessed in ten patients. Significant differences were found for LA volume and phasic function. The Bi-ALM significantly underestimated LA volume and overestimated LA function in comparison to Simpson's method (Bi-ALM vs. Simpson's method: LAV max : 80.18 vs. 98.80 ml; LAV pre-ac : 61.09 vs. 80.41 ml; LAV min : 36.85 vs. 52.66 ml; LAEF Total : 55.17 vs. 47.85%; LAEF Passive : 23.96 vs. 19.15%; LAEF Booster : 40.87 vs. 35.64%). LA volumetric and functional parameters were reproducible on an intra- and inter-observer levels for both methods. Intra-observer agreement for LA function was better for Simpson's method (Bi-ALM vs. Simpson's method; ICC LAEF Total : 0.84 vs. 0.96; ICC LAEF Passive : 0.74 vs. 0.92; ICC LAEF Booster : 0.86 vs. 0.89). The Bi-ALM is based on geometric assumptions that do not reflect the complex individual LA geometry. The assessment of transversal slices covering the left atrium with Simpson's method is feasible and might be more suitable for an accurate quantification of LA volume and phasic function.

Background: Severe hypoperfusion can cause lung damage. We studied the effects of regional perfusion block in normal lungs and in the lungs that had been conditioned by lavage with 500 ml saline and high V T (20 ml kg -1 ) ventilation., Methods: Nineteen pigs (61.2 ± 2.5 kg) were randomized to five groups: controls (n = 3), the right lower lobe block alone (n = 3), lavage and high V T (n = 4), lung lavage, and high V T plus perfusion block of the right (n = 5) or left (n = 4) lower lobe. Gas exchange, respiratory mechanics, and hemodynamics were measured hourly. After an 8-h observation period, CT scans were obtained at 0 and 15 cmH 2 O airway pressure., Results: Perfusion block did not damage healthy lungs. In conditioned lungs, the left perfusion block caused more edema in the contralateral lung (777 ± 62 g right lung vs 484 ± 204 g left; p < 0.05) than the right perfusion block did (581 ± 103 g right lung vs 484 ± 204 g left; p n.s.). The gas/tissue ratio, however, was similar (0.5 ± 0.3 and 0.8 ± 0.5; p n.s.). The lobes with perfusion block were not affected (gas/tissue ratio right 1.6 ± 0.9; left 1.7 ± 0.5, respectively). Pulmonary artery pressure, PaO 2 /FiO 2 , dead space, and lung mechanics were more markedly affected in animals with left perfusion block, while the gas/tissue ratios were similar in the non-occluded lobes., Conclusions: The right and left perfusion blocks caused the same "intensity" of edema in conditioned lungs. The total amount of edema in the two lungs differed because of differences in lung size. If capillary permeability is altered, increased blood flow may induce or increase edema.

Background: Endomyocardial biopsies (EMB) are an important diagnostic tool for myocarditis and other infiltrative cardiac diseases. Routinely, biopsies are obtained under fluoroscopic guidance with a substantial radiation burden. Despite procedural success, there is a large sampling error caused by missing the affected myocardium. Therefore, multiple (>6) biopsies are taken in the clinical setting. In cardiovascular magnetic resonance (CMR), late gadolinium enhancement (LGE) depicts areas of affected myocardium in myocarditis or in other infiltrative cardiomyopathies. Thus, targeted biopsy under real-time CMR image guidance might reduce the problem of sampling error., Methods: Seven minipigs of the Goettingen strain underwent radiofrequency ablation in the left ventricle. At least two focal lesions were induced on the lateral wall in five and the apex in two animals. Each ablation lesion was created by two consecutive 30 sec ablations (max. 30 W, temperature 60-64 °C). Biopsies were taken immediately after lesion induction using a commercially available 7 F conventional bioptome under fluoroscopic guidance at the ablation site. Afterwards the animals underwent CMR and lesion visualization by LGE at 3T. The lesions were then targeted and biopsied under CMR-guidance using a MR-conditional bioptome guided by a steerable catheter. Interactive real-time (RT) visualization of the intervention on an in-room monitor was based on radial FLASH with nonlinear inverse reconstruction (NLINV) at a temporal resolution of 42 ms. All samples underwent a standard histological evaluation., Results: Radiofrequency ablation was successful in all animals. Fluoroscopy-guided biopsies were performed with a success rate of 6/6 minipigs - resulting in a nonlethal pericardial effusion in one animal. Visualization of radiofrequency lesions by CMR was successful in 7/7 minipig, i.e. at least one lesion was clearly visible. Localization and tracking of the catheters and the bioptome using interactive control of the imaging plane was achieved in 6/6 MP; however in the animal with a large pericardial effusion after EMB under fluoroscopy no further EMB was attempted for safety reasons. Biopsies under interactive RT-CMR guidance were successfully performed in 5/6 animals, in one animal the bioptome reached the lesion, however the forceps did not cut out a sample. Specimens obtained under CMR guidance contained part of the lesion in 6/15 (40%) myocardial specimens and in 4/5 (80%) animals in which samples were achieved. Conventional biopsies revealed ablation lesions in 4/17 (23.5%) specimens in 3/6 minipigs (50%)., Conclusion: Focal lesions induced by radiofrequency ablation in a minipig model are a useful tool for CMR-guided biopsy studies. In contrast to fluoroscopy, CMR provides excellent visualization of lesions. Interactive real-time CMR allows excellent passive tracking of the instruments and EMB provides significantly superior sampling accuracy compared to fluoroscopy-guided biopsies. Nonetheless, further improvements of MR-compatible bioptomes and guiding catheters are essential before applying this method in a clinical setting.

Fingolimod is a an oral disease modifying drug for relapsing remitting multiple sclerosis (MS) preventing egress of B and T cells from lymph nodes. Relevant first dose adverse events include bradycardia and atrioventricular conduction slowing. Cardiac side effects of fingolimod and combinational pharmacotherapy including duloxetine and tolterodine were monitored in mice of different age using implantable ECG telemetric systems. Cardiac tissue was assessed for S1P-receptor subtype (1 and 3), and for GIRK1 expression. Fingolimod led to a significant heart rate reduction within 60 min, which returned to baseline values within 24 h. In older mice bradycardia was more pronounced compared to younger mice. Atrioventricular conduction was not affected. Older mice showed a higher S1PR3 expression in a naïve state and receptor expression was reduced after fingolimod administration. Combination with duloxetine or tolterodine alleviated fingolimod induced heart rate decrease. Our data provide preclinical evidence that negative chronotropic effects of fingolimod might be age dependent, possibly due to an altered expression and internalization of cardiac S1PR3 in older animals. This data could be relevant for future clinical monitoring and patient selection in the aging MS population. Combinational therapies of fingolimod and duloxetine or tolterodine are well tolerated and safe without an increased risk for pronounced bradycardia or arrhythmia.

Background: Chronic inflammatory demyelinating polyneuropathy (CIDP) is often associated with chronic disability, which can be accounted to incomplete regeneration of injured axons. We hypothesized that Schwann cell support for regenerating axons may be altered in CIDP, which may account for the poor clinical recovery seen in many patients., Methods: We exposed human and rodent Schwann cells to sera from CIDP patients and controls. In a model of chronic nerve denervation, we transplanted these conditioned Schwann cells intraneurally and assessed their capacity to support axonal regeneration by electrophysiology and morphometry., Results: CIDP-conditioned Schwann cells were less growth supportive for regenerating axons as compared to Schwann cells exposed to control sera. The loss of Schwann cell support was associated with lower levels of granulocyte-macrophage colony-stimulating factor (GM-CSF) in CIDP sera and correlated with altered expression of c-Jun and p57kip2 in Schwann cells. The inactivation of these regulatory factors resulted in an altered expression of neurotrophins including BDNF, GDNF, and NGF in CIDP-conditioned Schwann cells in vitro., Conclusions: Our study provides evidence that pro-regenerative functions of Schwann cells are affected in CIDP. It thereby offers a possible explanation for the clinical observation that in many CIDP patients recovery is incomplete despite sufficient immunosuppressive treatment.

Purpose: To reduce saturation effects in the arterial input function (AIF) estimation of quantitative myocardial first-pass saturation recovery perfusion imaging by employing a model-based reconstruction., Theory and Methods: Imaging was performed with a saturation recovery prepared radial FLASH sequence. A model-based reconstruction was applied for reconstruction. By exploiting prior knowledge about the relaxation process, an image series with different saturation recovery times was reconstructed. By evaluating images with an effective saturation time of approximately 3 ms, saturation effects in the AIF determination were reduced. In a volunteer study, this approach was compared with a standard prebolus technique., Results: In comparison to the low-dose injection of a prebolus acquisition, saturation effects were further reduced in the AIFs determined using the model-based approach. These effects, which were clearly visible for all six volunteers, were reflected in a statistically significant difference of up to 20% in the absolute perfusion values., Conclusion: The application of model-based reconstruction algorithms in quantitative myocardial perfusion imaging promises a significant improvement of the AIF determination. In addition to greatly reducing saturation effects that occur even for the prebolus methods, only a single bolus has to be applied. Magn Reson Med 76:880-887, 2016. © 2015 Wiley Periodicals, Inc., (© 2015 Wiley Periodicals, Inc.)

Purpose: In hepatocellular carcinoma patients with large or multinodal tumors, where curative treatment options are not feasible, transarterial therapies play a major role. Transarterial chemoembolization (TACE) with drug-eluting beads (DEB-TACE) is a promising new approach due to higher intratumoral and lower systemic concentration of the chemotherapeutic agent compared to conventional TACE (cTACE)., Patients and Methods: In a retrospective analysis, 32 patients with hepatocellular carcinoma who received either DEB or a cTACE were compared regarding survival time, disease recurrence, and side effects such as pain and fever., Results: No significant differences could be detected between the cTACE and DEB-TACE groups with regard to mean hospital stay, appearance of postinterventional fever, or 30-day mortality. However, the application of intravenous analgesics as postinterventional pain medication was needed more often in patients treated with DEB-TACE (57.1% vs 12.5%, P=0.0281). The overall median survival after the initial procedure was 10.8 months in the cTACE group and 9.2 months in the DEB-TACE group, showing no significant difference., Conclusion: No survival benefit for patients treated with either DEB-TACE or cTACE was observed. Surprisingly, a higher rate of postinterventional pain could be detected after DEB-TACE.

Background: Our study is the first evaluation of nodal metastatic prostate cancer (PCa) to mesorectal lymph nodes (MLN) detected by (68) Ga-PSMA-PET/CT., Methods: We retrospectively analyzed 76 consecutive PCa patients who underwent (68) Ga-PSMA-PET/CT: 61 PCa patients with biochemical recurrence (BCR) after curative treatment and 15 high-risk PCa before primary therapy. We assessed PET-positive MLN, which are indicative for PCa., Results: We detected PET-positive lesions for PCa in (68) Ga-PSMA-PET/CT in 66 of 76 (87%) patients. Nodal disease was imaged in 47 of 66 (71%) patients. Indicative mesorectal nodal lesions for PCa were detected in 12 of 76 (15.8%) patients. The median number of PET-positive MLN was one per patient. Seven of twelve patients had recurrent PCa after radical prostatectomy with a median PSA value of 1.84 ng/ml (range 0.31-13). Five of twelve patients had untreated first diagnosed high-risk PCa with median PSA value of 90 ng/ml (range 4.6-93) at PET/CT, respectively. For all PET positive MLN a morphological correlate was found in CT (shortest diameter median 4 mm [range 4-21]; longest diameter median 7.5 mm [range 5-25]). After PET/CT, four patients with recurrent PCa received hormonal therapy, one patient was treated with directed radiation therapy of MLN, one patient received chemotherapy, and one patient was treated with pelvic lymph node dissection. Three high-risk PCa patients received hormonal therapy, and two patients were treated with adjuvant hormonal therapy after radical prostatectomy., Conclusions: Detection and exact location of nodal metastasis for PCa is crucial for the choice of treatment and the patient's prognosis. (68) Ga-PSMA-PET/CT seems to improve the detection of nodal metastasis in PCa, especially concerning mesorectal lymph nodes., (© 2016 Wiley Periodicals, Inc.)

Purpose: Binding of (68)Ga-PSMA-HBED-CC ((68)Ga-PSMA) at prostate cancer (PC) cells increases over time. A biphasic protocol may help separating benign from tumor lesions. The aim of this study was the retrospective evaluation of a diagnostic incremental value of a dual-time point (biphasic) (68)Ga-PSMA-PET/CT in patients with prostate cancer., Methods: Retrospective analysis of 35 consecutive patients (49-78 years, median 71) with newly diagnosed PC (12/35) or recurrence of PC (23/35). PET/CT (Gemini TF16, Philips) was acquired 1 h and 3 h p. i. of 140-392 MBq (300 MBq median) (68)Ga-PSMA, followed by a diagnostic contrast CT. PET findings were correlated with histology or unequivocal CT findings. Semiquantitative PET data (SUVmax, SUV mean) were acquired and target-to-background-ratios (T/B-ratio) were calculated for benign and malign lesions for both time points. Size of lymph nodes (LN) on diagnostic CT was recorded. Statistical analysis was performed for assessment of significant changes of semiquantitative PET-parameters over time and for correlation of size and uptake of lymph nodes., Results: One hundred and four lesions were evaluated. Sixty lesions were referenced by histology or unequivocal CT findings, including eight (13.3 %) histopathologically benign lymph nodes, 12 (20 %) histopathologically lymph node metastases, 12 (20 %) primary tumors, three (5 %) local recurrences, and 25 (41.7 %) bone metastases. Forty-four lesions were axillary LN with normal CT-appearance. Benign lesions had significantly lower SUVmax and T/B-ratios compared with malignant findings. Malign lesions showed a significant increase of both parameters over time compared to benign findings. There was no correlation between LN size and SUVmax. The sensitivity, specificity, the positive predictive value and negative predictive value of PET/CT regarding pelvic LN was 94 %, 99 %, 89 %, and 99.5 %, respectively., Conclusions: In contrast to benign tissues, the uptake of proven tumor lesions increases on (68)Ga-PSMA-PET/CT over time. A biphasic PET-study may lead to a better detection of tumor lesions in unequivocal findings.

This study examines the prevalence of comorbid physical health conditions within a community sample of individuals with severe mental illness (SMI), compares them to a matched national sample without SMI, and identifies which comorbidities create the greatest disease burden for those with SMI. Self-reported health status, co-morbid medical conditions and perceived disease burden were collected from 203 adults with SMI. Prevalence of chronic health conditions was compared to a propensity-matched sample without SMI from the National Comorbidity Survey-Replication (NCS-R). Compared to NCS-R sample without SMI, our sample with SMI had a higher prevalence of seven out of nine categories of chronic health conditions. Chronic pain and headaches, as well as the number of chronic conditions, were associated with increased disease burden for individuals with SMI. Further investigation of possible interventions, including effective pain management, is needed to improve the health status of this population.

The two primary goals of mental health courts are to engage individuals with severe mental illness in the criminal justice system with clinical mental health services and to prevent future involvement with the criminal justice system. An important factor in helping to achieve both goals is to identify participants' level of clinical needs and criminogenic risk/needs. This study seeks to better understand how criminogenic risk affects outcomes in a mental health court. Specifically, we explore if high criminogenic risk is associated with failure to complete mental health court. Our subjects are participants of a municipal mental health court (MHC) who completed the Level of Services Inventory-Revised (LSI-R) upon entry to the program (N=146). We used binary logistic regression to determine the association between termination from the program with the total LSI-R. Our findings suggest that, net of prior criminal history, time in the program and clinical services received, high criminogenic risk/need is associated with failure to complete mental health court. In addition to providing clinical services, our findings suggest the need for MHCs to include criminogenic risk assessment to identify criminogenic risk. For participants to succeed in MHCs, both their clinical and criminogenic needs should be addressed., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

Objective: The aims of this study were to compare 3 contrast agents and to define feasible doses for quantitative lung perfusion imaging using the dual-bolus approach in dynamic contrast-enhanced (DCE) magnetic resonance imaging (MRI)., Materials and Methods: Ten healthy volunteers (6 males, 4 females; mean age, 23.5 years) underwent DCE-MRI at 1.5 T using a 3D FLASH sequence. After a prebolus, 3 doses of gadopentetate dimeglumine (Gd-DTPA), gadofosveset, and gadobenate dimeglumine (Gd-BOPTA) were evaluated. Dose regimes were as follows: Gd-DTPA: 3.0 mL, 6.0 mL, and 12.0 mL with 1.5 mL prebolus; gadofosveset: 1.5 mL, 3.0 mL, and 6.0 mL with 0.8 mL prebolus; and Gd-BOPTA: 1.5 mL, 3.0 mL, and 6.0 mL with 0.8 mL prebolus. Pulmonary blood flow (PBF), pulmonary distribution volume, and mean transit time were assessed for each bolus. Region of interest measurements were used to determine the arterial input function (AIF) in the pulmonary trunk and signal intensities in lung parenchyma. Two radiologists independently rated the subjective image quality of the quantitative perfusion maps based on a 4-point Likert scale., Results: Dose-dependent signal saturation effects were observed for all 3 contrast agents concerning AIF and parenchyma measurements. Signal yields were comparable using Gd-BOPTA (AIF, 214.49 arbitrary units [AU]; parenchyma, 41.7 AU) and Gd-DTPA (207.43 AU; 36.3 AU). Gadofosveset showed significantly lower signal yield (165.74 AU; 25.2 AU; p < 0.008). Highest signal increase was observed for Gd-DTPA. Using Gd-DTPA, mean PBF values for the 3 doses (3 mL, 6 mL, 12 mL) in mL/min per milliliter lung volume were 2.9 ± 1.5, 2.4 ± 1.1, and 1.6 ± 1.0. For the 3 doses of gadofosveset (1.5 mL, 3 mL, 6 mL) mean PBF results were 3.1 ± 1.1, 1.9 ± 0.7, and 1.2 ± 0.6. Last, mean PBF values for Gd-BOPTA (1.5 mL, 3 mL, 6 mL) were 3.4 ± 1.7, 2.8 ± 1.3, and 2.0 ± 0.8. Measurements provided consistent values for all perfusion parameters (PBF, pulmonary distribution volume, mean transit time) when compared with reference literature. Contrast dose volume and the applied contrast agent had no relevant effects on the image quality scores., Conclusions: The dual-bolus approach using a 3D FLASH sequence is a feasible tool for quantitative lung perfusion imaging. Small boluses of 3 mL for Gd-DTPA, 1.5 mL for Gd-BOPTA, and 1.5 mL for gadofosveset provide sufficient signal yield for quantitative parenchyma measurements. Using higher boluses falsely lower perfusion values have to be considered due to signal saturation effects. Although gadofosveset yielded the lowest signal, the generated quantitative perfusion maps were of diagnostic quality.

Trauma during childhood and adolescence is a common event among people with a serious psychological disorder. Few studies assess a wide range of stressors for this population. This is surprising given that these stressful events are implicated in poorer outcomes related to course and treatment of mental health problems. This study of 214 people with serious mental illness examines the prevalence of childhood traumas, perceived neighborhood problems, discrimination, chronic strains, negative life events, and daily hassles. We use regression analyses to determine if these stressors are associated with quality of life. Results show that 95% of the sample report at least one childhood adversity. Perceived neighborhood problems, experiences of discrimination, chronic strains, life events, and daily hassles were also common. Examining the relationship between demographic factors and stressors suggests that older respondents, Whites, those who have never been married, and people diagnosed with Schizophrenia reported fewer stressors compared to those who are older, non-White, ever married, or suffering from other types of mental health problems. Finally, three of the six types of stressors were related to lower quality of life and depression. We discuss the implications of these findings for the treatment of severe psychological problems.

Background: In spite of several research studies help to describe the heart in Fabry disease (FD), the cardiomyopathy is not entirely understood. In addition, the impact of blood pressure and alterations in geometry have not been systematically evaluated., Methods: In 74 FD patients (mean age 36±12 years; 45 females) the extent of myocardial fibrosis and its progression were quantified using cardiac magnetic-resonance-imaging with late enhancement technique (LE). Results were compared to standard echocardiography complemented by 2D-speckle-tracking, 3D-sphericity-index (SI) and standardized blood pressure measurement. At baseline, no patient received enzyme replacement therapy (ERT). After 51±24 months, a follow-up examination was performed., Results: Systolic blood pressure (SBP) was higher in patients with vs. without LE: 123±17 mmHg vs. 115±13 mmHg; P = 0.04. A positive correlation was found between SI and the amount of LE-positive myocardium (r = 0.51; P<0.001) indicating an association of higher SI in more advanced stages of the cardiomyopathy. SI at baseline was positively associated with the increase of LE-positive myocardium during follow-up. The highest SBP (125±19 mmHg) and also the highest SI (0.32±0.05) was found in the subgroup with a rapidly increasing LE (ie, ≥0.2% per year; n = 16; P = 0.04). Multivariate logistic regression analysis including SI, SBP, EF, left ventricular volumes, wall thickness and NT-proBNP adjusted for age and sex showed SI as the most powerful parameter to detect rapid progression of LE (AUC = 0.785; P<0.05)., Conclusions: LV geometry as assessed by the sphericity index is altered in relation to the stage of the Fabry cardiomyopathy. Although patients with FD are not hypertensive, the SBP has a clear impact on the progression of the cardiomyopathy.

Background: In Fabry cardiomyopathy, little is known about the interaction between its key feature of myocardial replacement fibrosis and changes in resting, Holter, and exercise electrocardiography (-ECG)., Methods and Results: Resting ECG, 24-h Holter ECG, and exercise ECG were performed in 95 patients (50 women) with Fabry disease, staged using cardiac magnetic resonance imaging to measure left ventricular fibrosis. With resting ECG, T alterations were seen in patients with cardiac fibrosis, while time intervals and rhythm were unchanged (except for a longer QRS duration in patients with severe fibrosis). All patients with severe fibrosis showed T inversion, ST alteration, or both. With Holter ECG, maximum and minimum heart rate did not differ with fibrosis severity. Patients without fibrotic tissue showed less ventricular premature beats (VPB) (median 5/24 h) compared to those with mild (median 11/24 h) or severe fibrosis (median 115/24 h; P < 0.05, respectively). Fibrosis was a strong predictor of VPB burden (r 2  = 0.5; P < 0.001). During exercise, patients with severe fibrosis had the least increase in systolic blood pressure (sBP) (47 ± 22 mmHg vs. 62 ± 25 mmHg, P < 0.05) and the lowest maximum heart rate (113 ± 18/min; P < 0.05). Patients with mild fibrosis had a high sBP during exercise (198 ± 37 mmHg; P < 0.05). Decreased diastolic blood pressure (>10 mmHg) occurred in some patients with no (3/41) or mild fibrosis (3/34) but not in patients with severe fibrosis (0/20; P < 0.01)., Conclusions: Our data suggest that cardiac replacement fibrosis is responsible for repolarization abnormalities on resting ECG and increased VPB with Holter ECG. During exercise ECG, advanced cardiomyopathy is characterized by chronotropic incompetence with limitations on blood pressure and heart rate increase.

Paclitaxel is an integral component of solid tumor treatment. This chemotherapeutic agent provokes an often irreversible peripheral sensory neuropathy with pathological features of distal axonal degeneration. Current pathological concepts assume that polymerization of axonal microtubules and mitochondrial dysfunction contributes to the development of paclitaxel-induced peripheral neuropathy. The relationship, however, between microtubule stabilization, mitotoxicity and axonal degeneration is still not completely understood. To explore the function of axonal mitochondria we treated transgenic mice that harbor cyan fluorescent protein (CFP)-labeled neuronal mitochondria with repeated doses of paclitaxel and assessed neuropathic changes by nerve conduction and histological studies. In addition, mitochondrial content and morphology was determined by ex vivo imaging of axons containing CFP-labeled mitochondria. Using quantitative RT-PCR and fluorescence-labeled mRNA we determined axonal mRNA transport of nuclear encoded mitochondrial proteins. Prolonged treatment with high doses of paclitaxel-induced a predominant sensory neuropathy in mice. Although mitochondrial velocity in axons per se was not altered, we observed significant changes in mitochondrial morphology, suggesting that paclitaxel treatment impairs the dynamics of axonal mitochondria. These changes were caused by decreased levels of nuclear encoded mRNA, including the mitochondrial fusion/fission machinery. Moreover, impaired axonal mRNA transport in vitro resulted in mitochondrial dysfunction and subsequent axonal degeneration. Taken together, our experiments provide evidence that disrupted axonal transport of nuclear derived mRNA plays a crucial role in the pathogenesis of paclitaxel-induced sensory neuropathy., (Copyright © 2015. Published by Elsevier Inc.)

Background: Patients with autosomal-recessively inherited Friedreich's ataxia (FA) may develop a hypertrophic cardiomyopathy (CM), which potentially progresses towards a life-limiting problem. The typical features of this CM and the sequence of progression are widely unknown., Methods: Thirty-two consecutive patients with genetically confirmed FA were included. All patients received resting electrocardiogram (ECG), 24-hour Holter-ECG, echocardiography with speckle tracking imaging, cardiac magnetic resonance imaging (cMRI) with late enhancement imaging (for replacement fibrosis), and measurement of high-sensitive troponin-T (hsTNT). In addition, morphological parameters were retrospectively compared to data obtained five years before., Results: Based on criteria comprising ejection fraction (<55%), left ventricular end-diastolic posterior wall thickness (LVPWT ≥ 11 mm), fibrosis on cMRI, hsTNT ≥ 14 ng/ml, or T-wave-inversion, in all but two patients a CM could be detected (94%). Using these criteria we propose the following staging: a) mild CM (n=5, 16%; T-wave-inversion only); b) intermediate CM (n=4, 13%; T-wave-inversion with hypertrophy but no fibrosis); c) severe CM (n=13, 41%; fibrosis with raised hsTNT); and d) end-stage CM (n=8; 25%; ejection-fraction<55%). All patients with end-stage CM also showed fibrosis on cMRI, T-wave-inversion, marked elevation in hsTNT, and a decrease in LVPWT during the last five years (from 10.7 ± 1.2mm to 9.5 ± 1.3mm, p=0.025). In addition, 38% suffered from supraventricular tachycardia on Holter-ECG., Conclusions: A comprehensive cardiac assessment will unravel established CM in almost all patients with FA with electrocardiographic abnormalities as earliest signs. Advanced stages can be characterized by elevated hsTNT and replacement fibrosis leading to recession of hypertrophy, reduction of global myocardial function, and electrical instability., (Copyright © 2015. Published by Elsevier Ireland Ltd.)

Background: Intravenous immunoglobulin (IVIg) is an effective treatment in chronic inflammatory demyelinating polyneuropathy (CIDP). In most patients, the optimal IVIg dose and regime is unknown. Polyvalent immunoglobulin (Ig) G form idiotypic/anti-idiotypic antibody pairs in serum and IVIg preparations. We determined IgG dimer levels before and after IVIg treatment in CIDP patients with the aim to explore their utility to serve as a surrogate marker for treatment response., Methods: IgG was purified from serum of five controls without treatment, as well as from serum of 16 CIDP patients, two patients with Miller Fisher syndrome (MFS), and one patient with myasthenia gravis before and after treatment with IVIg. IgG dimer levels were determined by size exclusion chromatography. IgG dimer formation was correlated with clinical response to IVIg treatment in CIDP. Re-monomerized IgG dimer fractions were analyzed for immunoreactivity against peripheral nerve tissue., Results: IgG dimer levels were significantly higher in post- compared to pre-IVIg infusion samples. Low post-treatment IgG dimer levels in CIDP patients were associated with clinical worsening during IVIg treatment. Re-monomerized IgG dimer fractions from CIDP patients showed immunoreactivity against peripheral nerve tissue, whereas similarly treated samples from MFS patients showed immunoreactivity against GQ1b., Conclusion: Assessment of IgG dimer levels could be a novel approach to monitor CIDP patients during IVIg treatment, but further studies in larger cohorts are warranted to explore their utility to serve as a potential therapeutic biomarker for IVIg treatment response in CIDP.

Background and Objective: Neoadjuvant therapy could improve oncological outcome of patients suffering from colon cancer. An accurate staging method is needed to define suitable patients. The aim of this retrospective study was to validate the value of CT for identifying patients with local advanced (T3/4) or nodal-positive colon cancer., Methods and Material: Preoperative abdominal CT scans of 210 patients with colon cancer were evaluated by two radiologists independently for the T stage and N stage. Results were compared to pathology. Patients were stratified according to the guidelines for rectal cancer into patients with low risk (T0/1/2 and N0) or high risk (T3/4 or N+)., Results: Inter-observer correlation was high with over 90 %. Overall sensitivity T stage was 93.0 % and for N stage 76.9 %. Using CT scan to identify local advanced (T3/4 or N+) tumors, the consensus sensitivity was 94.9 %, the specificity 53.6 %, the positive predictive value (PPV) 92.8 %, and the negative predictive value (NPV) 62.5 %., Conclusion: Computer tomography represents an effective tool for identifying patients with colon cancer suitable for neoadjuvant therapy according to the guidelines for rectal cancer.