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Background: Relapse in pediatric acute myeloid leukemia (pedAML) patients is known to be associated with residual leukemic stem cells (LSC). We have previously shown that epithelial membrane protein 1 (EMP1) is significantly overexpressed in LSC compared to hematological stem cell fractions. EMP1 was also documented as part of the 17-gene stemness score and a 6-membrane protein gene score, both correlating high EMP1 expression with worse overall survival. However, its potential as a therapeutic target in pedAML is still unexplored., Methods: Association analyses of EMP1 expression with clinical and molecular AML characteristics were performed. Expression of EMP1 was evaluated in pedAML and cord blood samples. Expression in normal blood cells and tissues was evaluated by flow cytometry and immunohistochemistry, respectively., Results: In silico analyses showed variable mRNA expression of EMP1 in multiple pedAML datasets, and a significant correlation between high EMP1 transcript levels and the presence of inv(16). Flow cytometry showed overexpression of EMP1 in pedAML samples, as well as expression in normal blood subsets. Importantly, immunohistochemistry revealed EMP1 expression in multiple normal tissues., Conclusion: Although EMP1 presents as an interesting membrane-associated target in pedAML, its abundant expression in normal blood cells and tissues will impede it from further exploration as a therapeutic target., Impact: EMP1 is highly expressed in multiple cancer types, but expression in acute myeloid leukemia (AML) and normal tissues is unexplored. As EMP1 is investigated in other cancer types, expression in normal tissues and blood cells is relevant in predicting the success of EMP1-targeted therapies. In this study, we showed expression of EMP1 in multiple tissues, predicting high on-target off-tumor toxicity, which will warn other researchers of possible toxicities when generating EMP1-targeted therapy. Finally, we showed that high EMP1 expression is associated with better overall survival of pediatric AML patients, reducing the need for EMP1-targeted therapy., (© 2024. The Author(s), under exclusive licence to the International Pediatric Research Foundation, Inc.)

Conventional therapies for acute myeloid leukemia (AML) are characterized by high rates of relapse, severe toxicities, and poor overall survival rates. Thus, the development of new therapeutic strategies is crucial for improving the survival and quality of life of AML patients. CD19-directed chimeric antigen receptor (CAR) T-cell immunotherapy has been extremely successful in the treatment of B-cell acute lymphoid leukemia and several mature B-cell lymphomas. However, the use of CAR T-cell therapy for AML is currently prevented due to the lack of a myeloid equivalent to CD19, as currently known cell surface targets on leukemic blasts are also expressed on healthy hematopoietic stem and progenitor cells as well as their progeny. In addition, the immunosuppressive tumor microenvironment has a dampening effect on the antitumor activity of CAR-T cells. Here, we review the therapeutic challenges limiting the use of CAR T-cell therapy for AML and discuss promising novel strategies to overcome them., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2023 the Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the European Hematology Association.)

Pediatric acute myeloid leukemia (pedAML) is a heterogeneous blood cancer that affects children. Although survival rates have significantly improved over the past few decades, 20-30% of children will succumb due to treatment-related toxicity or relapse. The molecular characterization of the leukemic stem cell, shown to be responsible for relapse, is needed to improve treatment options and survival. Recently, it has become clear that non-coding RNAs, including long non-coding RNAs (lncRNAs) and microRNAs (miRNAs), play a role in the development of human diseases, including pediatric cancer. Nevertheless, non-coding RNA expression data in pedAML are scarce. Here, we explored lncRNA ( n = 30,168) and miRNA ( n = 627) expression in pedAML subpopulations (leukemic stem cells (LSCs) and leukemic blasts (L-blasts)) and their normal counterparts (hematopoietic stem cells and control myeloblasts). The potential regulatory activity of differentially expressed lncRNAs in LSCs (unique or shared with the L-blast comparison) on miRNAs was assessed. Moreover, pre-ranked gene set enrichment analyses of (anti-) correlated protein-coding genes were performed to predict the functional relevance of the differentially upregulated lncRNAs in LSCs (unique or shared with the L-blast comparison). In conclusion, this study provides a catalog of non-coding RNAs with a potential role in the pathogenesis of pedAML, paving the way for further translational research studies.

A previously healthy 46-year-old woman presented with a mass lesion between the bases of the fourth and fifth fingers of the right hand. The mass had grown progressively over 2 years and started to cause practical difficulties in everyday life. Imaging depicted a hypervascular and well-circumscribed soft tissue tumor with imaging characteristics of a sarcoma. The lesion was treated surgically. The final diagnosis of the specimen upon pathology was a myopericytoma, a benign smooth-muscle cell neoplasm. Myopericytoma is a rare disease entity; however, it is important because it can mimic more ominous conditions., (Copyright © 2019 American Society for Surgery of the Hand. Published by Elsevier Inc. All rights reserved.)

Purpose: To evaluate the performance and clinical feasibility of 0.25 mm resolution mode of a dual-energy photon-counting detector (PCD) computed tomography (CT) system for coronary stent imaging and to compare the results to state-of-the-art dual-energy energy-integrating detector (EID) CT., Materials and Methods: Coronary stents with different diameters (2.0-4.0 mm) were examined inside a coronary artery phantom consisting of plastic tubes filled with iodine-based and gadolinium-based contrast material diluted to approximate clinical concentrations (n = 18). EID images were acquired using 2nd and 3rd generation dual-source CT systems (SOMATOM Flash and SOMATOM Force, Siemens Healthcare) at 0.60 mm (defined as standard-resolution (SR)) isotropic voxel size. Radiation-dose matched PCD images were acquired using a human prototype PCD system (Siemens Healthcare) at 0.50 mm (SR) and 0.25 mm (HR) imaging modes. Images were reconstructed using optimized convolution kernels., Results: Dual-energy HR PCD images significantly better stent lumen visualization (median: 69.5%, IQR: 61.2-78.9%) over dual-energy EID, and standard-resolution PCD images (median: 53.2-57.4%, all P < 0.01). HR PCD acquisitions reconstructed at SR image voxel size showed 25.3% lower image noise compared to SR PCD acquisitions (P < 0.001). High-resolution iodine and gadolinium maps, as well as virtual monoenergetic images, were calculated from the PCD data and enabled estimation of contrast agent concentration in the lumen without interference from the coronary stent., Conclusion: HR spectral PCD imaging significantly improves coronary stent lumen visibility over dual-energy EID. When the PCD-HR data was reconstructed into standard voxel sizes (0.5 mm isotropic) the image noise decreased by 25% compared to SR acquisition of PCD. Both dual-energy systems were consistent in estimating contrast agent concentrations., (Copyright © 2018. Published by Elsevier Inc.)

Objective: To evaluate a dynamic contrast-enhanced CT-protocol and compare this method with standard of care monophasic portovenous CT for detection of colorectal liver metastases., Materials and Methods: A dynamic contrast-enhanced CT protocol was developed to detect liver metastasis in patients suffering from colorectal cancer, in clinical practice. The study was approved by the Hospital Ethics Committee. Written informed consent was obtained from all patients. 135 patients were included in this prospective study. All patients were naive to treatment. A dynamic contrast-enhanced CT was performed, followed by routine monophasic portovenous CT of thorax-abdomen-pelvis. 42 of these patients presented with liver metastasis. The number and lesion conspicuity of detected liver metastasis on dynamic contrast-enhanced CT using perfusion maps, was compared to monophasic CT., Results: 135 patients were included, of which 42 presented with metastases to the liver. Dynamic contrast-enhanced CT outperformed portovenous CT for detection as well as conspicuity of colorectal liver metastasis, at a relatively low dose increment. Wilcoxon Signed Rank test had a p-value of 0.016 and <0.001 respectively for detection and conspicuity of colorectal liver metastasis., Conclusion: Dynamic contrast-enhanced CT increases the detection of colorectal liver metastasis, especially for lesions smaller than 15 mm, when compared to monophasic portovenous CT. Dynamic contrast-enhanced CT also has the added advantage of improved lesion conspicuity, which can positively influence reader confidence and clinical workflow., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Aim: To determine the prevalence, characteristics and clinical course of pancreatic cystic neoplasms (PCNs) in liver transplantation (LT) recipients., Methods: We retrospectively studied consecutive patients who underwent LT between January 1998 to April 2016. Clinical and laboratory data were obtained from patient medical records. Imaging findings on computed tomography and magnetic resonance cholangiopancreatography were reviewed by two radiologists., Results: During the study period, 872 patients underwent cadaveric LT. Pancreatic cysts were identified in 53/872 (6.1%) and 31/53 (58.5%) were PCNs [28 intraductal papillary mucinous neoplasm (IPMN), 2 mucinous cystic neoplasm (MCN), 1 serous cystadenoma]. Patients with PCNs exhibited less male predominance (55% vs 73%, P = 0.03) compared to patients without pancreatic cysts. Thirteen patients (42%) were diagnosed with PCN pre-LT while 18 patients (58%) developed PCN post-LT. The median size of PCNs was 13mm [interquartile range (IQR) 10-20 mm]. All IPMNs were side-branch type. Most PCNs were found in the head and body of pancreas (37% each), followed by the tail (25%). Five patients underwent further evaluation with endoscopic ultrasound. Progress imaging was performed on 81% of patients. PCNs remained stable in size and number in all but 2 patients. During a median follow up of 39 mo (IQR 26-58 mo), the 2 (6%) patients with MCN underwent pancreatectomy. No PCN patient developed pancreatic adenocarcinoma, while 5 died from illnesses unrelated to the PCN. Among patients without PCN, 1/841 (0.1%) developed pancreatic adenocarcinoma., Conclusion: The prevalence of PCNs in LT recipients was similar to the general population (3.6%, 31/872). Side-branch IPMNs do not appear to have accelerated malignant potential in post-LT patients, indicating the current surveillance guidelines are applicable to this group., Competing Interests: Conflict-of-interest statement: All authors have no conflicts of interest to declare with respect to this work.

Cognitive insight is the ability to re-evaluate thoughts and beliefs in order to make thoughtful conclusions. It differs from clinical insight, as it focuses on more general metacognitive processes. Therefore, it could be relevant to diverse disorders and non-clinical subjects. There is a growing body of research on cognitive insight in individuals with and without psychosis. This review has summarised the current state of the art regarding this topic. We conclude that while cognitive insight in its current form seems valid for use in individuals with psychosis, it is less so for individuals without psychosis. Additionally, higher cognitive insight not always leads to better psychological functioning. For instance, higher levels of self-reflection are often associated with depressive mood. We therefore recommend the sub-components of cognitive insight to be studied separately. Also, it is unclear what position cognitive insight takes within the spectrum of metacognitive processes and how it relates to other self-related concepts that have been defined previously in literature. Combining future and past research on cognitive insight and its analogue concepts will help in the formation of a uniform definition that fits all subjects discussed here., (Copyright © 2017. Published by Elsevier Ltd.)

A preterm neonate was born in our center, as a part of a diamniotic dichorionic twin pregnancy, complicated with placental abruption with need for urgent cesarean section at 26 weeks of gestation. After a difficult neonatal start with respiratory and cardiovascular problems, the neonate safely reached the neonatal intensive care unit. Further work-up and supportive care was continued. Transcranial ultrasound imaging through the anterior fontanel was part of this work-up. Initial examinations were not normal, and showed cystic lesions along the germinal matrix, without hydrocephalus or parenchymal lesions. The findings were highly suggestive of sequellae of grade II germinal matrix bleed according to Papile and Burstein (Image A). Further follow-up examinations by means of ultrasound depicted a discrete enlargement of the lateral ventricles over time (Image B). Later on development of widespread periventricular cystic lesions became apparent (Image C and D). The cystic lesions are located in the periventricular white matter, and are not attached to the ventricles. This finding makes cystic periventricular leukomalacia the preferred diagnosis, and makes venous infarction with cystic alterations secondary to germinal matrix bleeding less likely.

Objective: To give an overview of ear, nose, and throat (ENT) pathologies encountered in the emergency room (ER)., Methods: Retrospective analysis of 1296 files of patients visiting the ER between January 2008 and December 2012. Diagnosis, treatment, hospitalisation, referral, and demographic parameters were evaluated., Results: Epistaxis is the most frequent ENT condition seen in the ER. One third of epistaxis patients are on anticoagulant therapy. The second most frequent conditions observed were infections of the pharynx and tonsils. Nasal fractures and vertigo were also frequently observed., Conclusion: Epistaxis and its treatment were the most frequent ENT diagnosis and therapy seen in the ER. Infections are the main cause of hospitalisation. Referral to other disciplines and revisits seldom occurred.

The availability of detailed knee kinematic data during various activities can facilitate clinical studies of this joint. To describe in detail normal knee joint rotations in all three anatomical planes, 25 healthy subjects (aged 22-49 years) performed eleven motor tasks, including walking, step ascent and descent, each with and without sidestep or crossover turns, chair rise, mild and deep squats, and forward lunge. Kinematic data were obtained with a conventional lower-body gait analysis protocol over three trials per task. To assess the repeatability with standard indices, a representative subset of 10 subjects underwent three repetitions of the entire motion capture session. Extracted parameters with good repeatability included maximum and minimum axial rotation during turning, local extremes of the flexion curves during gait tasks, and stride times. These specific repeatable parameters can be used for task selection or power analysis when planning future clinical studies.

Introduction: Gap junctional intercellular communication has been implicated in the homeostatic regulation of cell growth, differentiation, and apoptosis. Cancer cells, which have been viewed as "partially blocked stem cells," and which lack the ability for growth control, terminal differentiation, and apoptosis, also lack functional gap junctional communication., Aims and Methodology: A clone of a human pancreatic ductal epithelial cell line, H6c7, derived after immortalization with human papilloma virus, was used to examine gap junctional intercellular communication and the ability to differentiate under different growth conditions., Results: The cells showed characteristic epithelial morphology on standard tissue culture dishes. When placed on Matrigel they showed phenotypical changes with extensive ductal organization and budding structures. In growth medium containing hormones and growth factors, these cells were gap junctional intercellular communication (GJIC)-incompetent. In the presence of c-AMP elevating agents, isobutylmethylxanthine, and forskolin, in basal medium that did not contain the hormones and growth factors, the cells became GJIC-competent and expressed connexin43 gap junction protein within 48 hours after treatment. RT-PCR analyses of the cells under different growth conditions showed that the cells expressed, and genes when cultured in the basal medium with c-AMP elevating agents. They also expressed the gene that did not change with c-AMP treatment. H6c7 cells also have the capacity to turn on an ectopic insulin promoter reporter gene., Conclusion: Our data suggest that the immortalized H6c7 cells retain stem-like characteristics and have the potential to differentiate into duct-like structures and perhaps insulin-producing cells.

Basic and advanced care of trauma patients has always been an important aspect of prehospital and immediate in-hospital emergency medicine, involving a broad spectrum of disciplines, specialties and skills delivered through Emergency Medical Services Systems which, however, may differ significantly in structure, resources and operation. This complex background has, at least in part, hindered the development of a uniform pattern or set of criteria and definitions. This in turn has hitherto rendered data incompatible, with the consequence that such differing systems or protocols of care cannot be readily evaluated or compared with acceptable validity. Guided by previous consensus processes evolved by the ERC, the AHA and other International Organizations--represented in ILCOR--on 'Uniform reporting of data following out-of-hospital and in-hospital cardiac arrest--the Utstein style' an international working group of ITACCS has drafted a document, 'Recommendations for uniform reporting of data following major trauma--the Utstein style'. The reporting system is based on the following considerations: A structured reporting system based on an "Utstein style template" which would permit the compilation of data and statistics on major trauma care, facilitating and validating independent or comparative audit of performance and quality of care (and enable groups to challenge performance statistics which did not take account of all relevant information). The recommendations and template should encompass both out-of-hospital and in-hospital trauma care. The recommendations and template should further permit intra- and inter-system evaluation to improve the quality of delivered care and identification of the relative benefits of different systems and innovative initiatives. The template should facilitate studies setting out to improve epidemiological understanding of trauma; for example such studies might focus on the factors that determine survival. The document is structured along the lines of the original Utstein Style Guidelines publication on 'prehospital cardiac arrest'. It includes a glossary of terms used in the prehospital and early hospital phase and definitions, time points and intervals. The document uses an almost identical scheme for illustrating the different process time clocks--one for the patient, one for the dispatch centre, one for the ambulance and, finally, one for the hospital. For clarity, data should be reported as core data (i.e. always obtained) and optional data (obtained under specific circumstances). In contrast to the graphic approach used for the Utstein template for pre- or in-hospital cardiac arrest, respectively, the present template introduces, for the time being, at least, a number of terms and definitions and a semantic rather than a graphic report form. The document includes the following sections: The Section Introduction and background The Section on Trauma Data Structure Development: presents a general outline of the development of structured data using object-orientated modelling (which will be discussed in due course) and includes a set of explanatory illustrations. The Section on Terms and Definitions: outlines terms and definitions in trauma care, describing different types of trauma (blunt, penetrating, long bone, major/combined, multiple/polytrauma and predominant trauma). The Section on Factors relating to the circumstances of the injury describes the following items: cause of injury (e.g. type of injury (blunt or penetrating), burns, cold, crush, laceration, amputation, radiation, multiple, etc. Severity of Injury e.g. prehospital basic abbreviated injury score developed by the working group. The score contains anatomical and physiological disability data, with the anatomical scale ranging ordinally from 1. Head to 9. External; the physiological disability scale ranging ordinally from 0--unsurvivable. Mechanism of injury recording for transportation incidents etc. e.g. the type of impact, po