Search

The intercostobrachial nerve (ICBN) is commonly defined as a purely sensory nerve supplying the skin of the lateral chest wall, axilla, and medial arm. However, numerous branching patterns and distributions, including motor, have been reported. This report describes an uncommon variant of the right ICBN observed in both an 86-year-old white female cadaver and a 77-year-old white male cadaver. In both cases the ICBN presented with an additional muscular branch, termed the "medial pectoral branch", piercing and therefore innervating the pectoralis major and minor muscles. Clinically, the ICBN is relevant during surgical access to the axilla and can result in sensory deficits (persistent pain/loss of sensory function) to this region following injury. However, damage to the variation observed in these cadavers may result in additional partial motor loss to pectoralis major and minor.

Liver cirrhosis is an established high-risk factor for HCC and the majority of patients diagnosed with HCC have cirrhosis. However, HCC also arises in non-cirrhotic livers in approximately 20 %of all cases. HCC in non-cirrhotic patients is often clinically silent and surveillance is usually not recommended. HCC is often diagnosed at an advanced stage in these patients. Current information about HCC in patients with non-cirrhotic liver is limited. Here we review the current knowledge on epidemiology, clinical features and imaging features of those patiens.

Study Objective To review the currently available methods for surgical and nonsurgical neovaginal creation with an additional focus on situations requiring vaginal stretching, replacement, or augmentation and the management of vaginal stenosis or stricture. Design Review of the existing literature Methods PUBMED search with key words vaginal agenesis, neovaginal creation, vaginoplasty, vaginal stretching, vaginal augmentation, vaginal stenosis, outcomes of vaginoplasty, Mullerian anomalies, vaginal anomalies Results The need to perform vaginal stretching, replacement, or augmentation will vary depending on the underlying reproductive tract condition. Conclusions A variety of techniques have been described to performed vaginal stretching, replacement, or augmentation. There are risks and benefits to each technique. Vaginal stricture and stenosis remain difficult problems given the high rates of these complications in patients undergoing these procedures. Although several techniques can alleviate this problem, they rely on the thickness of the stenosis and the location of the stenosis within the vagina.

Background COVID-19 pandemic had a substantial impact on surgical training programs.. This study describes the teaching strategies and outcomes in 3 different times of the COVID-19 pandemic through a dynamic assessment of medical skills and well-being of trainees. Methods Three surveys were administered during 2020 to General Surgery residents and fellows in a University Hospital in Argentina. Perceptions on the impact of COVID-19 were described. The stress rate and risk factors were analyzed. Results The study included 124 answers; 59% were men. 82% of trainees reported concerns about the loss of surgical skills in early phase 1. Time spent with academic activities increased in 94.5% of the cases. Due to the prompt implementation of changes, by the end of 2020, 73% participated in a greater number of procedures (p=0.003); Personal Protective Equipment (PPE) use related problems dropped from 40 to 14% (p=0.031) and the lack of adequate spaces where trainees could express reduced from 28% to zero. Half of the trainees felt stressed and 18% required psychological assistance; reporting problems with PPE use was identified as a risk factor (p=0.012). Conclusions Assessing trainees’ perceptions at 3 different times of the COVID-19 pandemic enabled the implementation of dynamic changes. The negative impact on surgical training was partially offset by the optimal use of virtual learning. Half of them felt stressed, identifying problems in the use of PPE as a predisposing factor., The evaluation of trainees’ perceptions at 3 different times of the pandemic enabled dynamic changes to be implemented; the negative impact on surgical training was partially offset by the optimal use of virtual learning. Increasing training on personal protective equipment use and guaranteeing spaces where trainees can express are mandatory to face pandemic without a clear endpoint.

To improve management of head and neck squamous cell carcinoma patients, we need to increase our understanding of carcinogenesis, to identify biomarkers, and drug targets. This study aimed to identify novel biomarkers by providing transcriptomics profiles of matched primary tumors, lymph node metastasis, and non-malignant tissue of 20 HNSCC patients as well as by bioinformatic analyses of a TCGA HNSCC cohort, comprising 554 patients. We provide cancer cell signaling networks differentially expressed in tumors versus metastases, such as mesenchymal–epithelial transition, and structural integrity networks. As a proof of principle study, we exploited the data sets and performed functional analyses of a novel cytokeratin, cytokeratin24 (cKRT24), which had not been described as biomarker for tumors before. Survival analysis revealed that low cKRT24 expression correlated with poor overall survival in HNSCC. Experimentally, downregulation of cKRT24 in primary tumors, metastases, and HNSCC cell lines was verified on mRNA and protein level. Cloning and ectopic overexpression of cKRT24 not only affected viability and growth of HNSSC cell lines, but also inhibited tumor growth in murine xenograft studies. We conclude that cKRT24 functions as a tumor suppressor in HNSCC, and may serve as an additional prognostic biomarker and novel target to support current HNSCC treatments.

Journal of synchrotron radiation 28(5), 28 (2021). doi:10.1107/S1600577521007335, The European XFEL delivers up to 27000 intense (>1012 photons) pulses per second, of ultrashort (≤50 fs) and transversely coherent X-ray radiation, at a maximum repetition rate of 4.5 MHz. Its unique X-ray beam parameters enable groundbreaking experiments in matter at extreme conditions at the High Energy Density (HED) scientific instrument. The performance of the HED instrument during its first two years of operation, its scientific remit, as well as ongoing installations towards full operation are presented. Scientific goals of HED include the investigation of extreme states of matter created by intense laser pulses, diamond anvil cells, or pulsed magnets, and ultrafast X-ray methods that allow their diagnosis using self-amplified spontaneous emission between 5 and 25 keV, coupled with X-ray monochromators and optional seeded beam operation. The HED instrument provides two target chambers, X-ray spectrometers for emission and scattering, X-ray detectors, and a timing tool to correct for residual timing jitter between laser and X-ray pulses., Published by Wiley-Blackwell, [S.l.]

This is the fifth in a series of papers entitled 'Controversies in EUS.' In the current paper, we deal with high-resolution catheter probes, otherwise known as EUS miniprobes (EUS-MPs). The application of miniprobes for early carcinomas in the entire intestinal tract, for subepithelial lesions, and for findings in the bile duct and pancreatic duct as well as endobronchial use is critically discussed. Submucous lesions, especially in the colon, but also early carcinomas in special cases are considered the most important indications. The argument is illustrated by numerous examples.

Background In recent studies, convolutional neural networks (CNNs) outperformed dermatologists in distinguishing dermoscopic images of melanoma and nevi. In these studies, dermatologists and artificial intelligence were considered as opponents. However, the combination of classifiers frequently yields superior results, both in machine learning and among humans. In this study, we investigated the potential benefit of combining human and artificial intelligence for skin cancer classification. Methods Using 11,444 dermoscopic images, which were divided into five diagnostic categories, novel deep learning techniques were used to train a single CNN. Then, both 112 dermatologists of 13 German university hospitals and the trained CNN independently classified a set of 300 biopsy-verified skin lesions into those five classes. Taking into account the certainty of the decisions, the two independently determined diagnoses were combined to a new classifier with the help of a gradient boosting method. The primary end-point of the study was the correct classification of the images into five designated categories, whereas the secondary end-point was the correct classification of lesions as either benign or malignant (binary classification). Findings Regarding the multiclass task, the combination of man and machine achieved an accuracy of 82.95%. This was 1.36% higher than the best of the two individual classifiers (81.59% achieved by the CNN). Owing to the class imbalance in the binary problem, sensitivity, but not accuracy, was examined and demonstrated to be superior (89%) to the best individual classifier (CNN with 86.1%). The specificity in the combined classifier decreased from 89.2% to 84%. However, at an equal sensitivity of 89%, the CNN achieved a specificity of only 81.5% Interpretation Our findings indicate that the combination of human and artificial intelligence achieves superior results over the independent results of both of these systems.

This study investigated whether vitamin D is associated with the presence or severity of chronic tic disorders and their psychiatric comorbidities. This cross-sectional study compared serum 25-hydroxyvitamin D [25(OH)D] (ng/ml) levels among three groups: children and adolescents (3–16 years) with CTD (n = 327); first-degree relatives (3–10 years) of individuals with CTD who were assessed for a period of up to 7 years for possible onset of tics and developed tics within this period (n = 31); and first-degree relatives who did not develop tics and were ≥ 10 years old at their last assessment (n = 93). The relationship between 25(OH)D and the presence and severity of tics, as well as comorbid obsessive–compulsive disorder (OCD) and attention-deficit/hyperactivity disorder (ADHD), were analysed controlling for age, sex, season, centre, latitude, family relatedness, and comorbidities. When comparing the CTD cohort to the unaffected cohort, the observed result was contrary to the one expected: a 10 ng/ml increase in 25(OH)D was associated with higher odds of having CTD (OR 2.08, 95% CI 1.27–3.42, p p = 0.01) and was inversely associated with ADHD symptom severity (β = − 2.52, 95% CI − 4.16–0.88, p

On the Ground • The BLM Assessment, Inventory, and Monitoring (AIM) strategy recommends five principles for building multiscale monitoring programs: standardized methods and indicators; data management and stewardship; appropriate sample designs; remote sensing integration; and structured implementation. These principles guide monitoring across public lands. • We find the AIM principles are sound and worthy of consideration for design and adaptation of rangeland monitoring programs worldwide. • An emergent principle, standard workflows and analysis frameworks for using data, connects data to land management decision-making and empowers land managers. • The AIM principles inspire and provide opportunities for the rangeland management community to implement adaptive management.

Cancer treatment related injury to the central nervous system (CNS) is well-recognized in the setting of brain-directed radiation therapies and conventional and novel systemic anticancer therapies. Late-delayed treatment-induced CNS complications frequently result in permanent neurologic disability. Therapeutic options are supportive with limited clinical benefit, whereby alteration or discontinuation of the overall antineoplastic treatment plan is frequently necessary to prevent further neurologic injury. Better identification of patients at high risk for developing late CNS toxicities, neuroprotective strategies with modification of existing antineoplastic treatment regimens, and research efforts directed at earlier recognition and improved treatment of central neurologic complications are paramount.

BackgroundChronic pain diseases are characterised by an ongoing and fluctuating endogenous pain, yet it remains to be elucidated how this is reflected by the dynamics of ongoing functional cortical connections. The present study addresses this disparity by taking the individual perspective of pain patients into account, which is the varying intensity of endogenous pain.MethodsTo this end, we investigated the cortical encoding of 20 chronic back pain patients and 20 chronic migraineurs in four repeated fMRI sessions. During the recording, the patients were asked to continuously rate their pain intensity. A brain parcellation approach subdivided the whole brain into 408 regions. A 10 s sliding-window connectivity analysis computed the pair-wise and time-varying connectivity between all brain regions across the entire recording period. Linear mixed effects models were fitted for each pair of brain regions to explore the relationship between cortical connectivity and the observed trajectory of the patients’ fluctuating endogenous pain.ResultsTwo pain processing entities were taken into account: pain intensity (high, middle, low pain) and the direction of pain intensity changes (rising vs. falling pain). Overall, we found that periods of high and increasing pain were predominantly related to low cortical connectivity. For chronic back pain this applies to the pain intensity-related connectivity for limbic and cingulate areas, and for the precuneus. The change of pain intensity was subserved by connections in left parietal opercular regions, right insular regions, as well as large parts of the parietal, cingular and motor cortices. The change of pain intensity direction in chronic migraine was reflected by decreasing connectivity between the anterior insular cortex and orbitofrontal areas, as well as between the PCC and frontal and ACC regions.ConclusionsInterestingly, the group results were not mirrored by the individual patterns of pain-related connectivity, which is suggested to deny the idea of a common neuronal core problem for chronic pain diseases. In a similar vein, our findings are supported by the experience of clinicians, who encounter patients with a unique composition of characteristics: personality traits, various combinations of symptoms, and a wide range of individual responses to treatment. The diversity of the individual cortical signatures of chronic pain encoding results adds to the understanding of chronic pain as a complex and multifaceted disease. The present findings support recent developments for more personalised medicine.

Three reports address the protection of the vulnerable population of patients with hematologic malignancies in the face of the ongoing COVID pandemic. The reports suggest that some patients who fail to mount a B-cell response to vaccine may nevertheless have protective T cell responses. As a group, these reports suggest that patients should continue to be immunized with additional doses to attempt to improve immune response but that they need to maintain the precautions recommended for the unvaccinated.

The current conceptualization of Alzheimer disease (AD) is driven by the amyloid hypothesis, in which a deterministic chain of events leads from amyloid deposition and then tau deposition to neurodegeneration and progressive cognitive impairment. This model fits autosomal dominant AD but is less applicable to sporadic AD. Owing to emerging information regarding the complex biology of AD and the challenges of developing amyloid-targeting drugs, the amyloid hypothesis needs to be reconsidered. Here we propose a probabilistic model of AD in which three variants of AD (autosomal dominant AD, APOE e4-related sporadic AD and APOE e4-unrelated sporadic AD) feature decreasing penetrance and decreasing weight of the amyloid pathophysiological cascade, and increasing weight of stochastic factors (environmental exposures and lower-risk genes). Together, these variants account for a large share of the neuropathological and clinical variability observed in people with AD. The implementation of this model in research might lead to a better understanding of disease pathophysiology, a revision of the current clinical taxonomy and accelerated development of strategies to prevent and treat AD. The amyloid hypothesis has been the dominant model for the pathogenesis of Alzheimer disease for several decades. In this Perspective, Giovanni Frisoni and colleagues examine evidence for and against this hypothesis before outlining an alternative model, the probabilistic model of Alzheimer disease.

Current evidence is insufficient to support different hypertension treatment targets in older adults. We evaluated whether frailty modifies the association between systolic blood pressure (SBP) and 8-year all-cause mortality in community-dwelling older adults. Longitudinal data from the ActiFE Ulm study (Activity and Function in the Elderly in Ulm; Germany) was collected. The association between SBP and mortality was analyzed using Cox proportional hazards models adjusted for age, sex, education, smoking, alcohol consumption, sleep disturbance, diastolic blood pressure, and antihypertensive medications, evaluating the presence of effect modification by frailty according to a frailty index based on the accumulation of deficits. Among 1170 participants (median age 73.9 years, 41.6% women), the prevalence of history of hypertension was 53.8% (median SBP, 144.0 mm Hg [interquartile range, 135.0–149.5], median diastolic blood pressure 78.0 mm Hg [interquartile range, 71.0–86.5]). The median follow-up time was 8.1 years, detecting 268 deaths. We identified 251 (21.5%, 114 deaths) frail participants (frailty index ≥0.2). Effect modification by frailty was detected. Among non-frail a J-shaped association was found with hazard ratio, 4.01 (95% CI, 1.13–14.28) for SBP

Key Points HMB is associated with rare and common variants in genes related to anemias and bleeding disorders.These are the first exome-sequencing results from patients with HMB, as well as their comparison with control exomes., Visual Abstract, Adolescents with low von Willebrand factor (VWF) levels and heavy menstrual bleeding (HMB) experience significant morbidity. There is a need to better characterize these patients genetically and improve our understanding of the pathophysiology of bleeding. We performed whole-exome sequencing on 86 postmenarchal patients diagnosed with low VWF levels (30-50 IU/dL) and HMB and compared them with 660 in-house controls. We compared the number of rare stop-gain/stop-loss and rare ClinVar “pathogenic” variants between cases and controls, as well as performed gene burden and gene-set burden analyses. We found an enrichment in cases of rare stop-gain/stop-loss variants in genes involved in bleeding disorders and an enrichment of rare ClinVar “pathogenic” variants in genes involved in anemias. The 2 most significant genes in the gene burden analysis, CFB and DNASE2, are associated with atypical hemolytic uremia and severe anemia, respectively. VWF also surpassed exome-wide significance in the gene burden analysis (P = 7.31 × 10−6). Gene-set burden analysis revealed an enrichment of rare nonsynonymous variants in cases in several hematologically relevant pathways. Further, common variants in FERMT2, a gene involved in the regulation of hemostasis and angiogenesis, surpassed genome-wide significance. We demonstrate that adolescents with HMB and low VWF have an excess of rare nonsynonymous and pathogenic variants in genes involved in bleeding disorders and anemia. Variants of variable penetrance in these genes may contribute to the spectrum of phenotypes observed in patients with HMB and could partially explain the bleeding phenotype. By identifying patients with HMB who possess these variants, we may be able to improve risk stratification and patient outcomes.

Background Overall survival (OS) for malignant pleural mesothelioma (MPM) in vulnerable subgroups remains poorly understood with scarce data available to guide treatment decisions. The study describes real-world detailed treatment patterns and outcomes of patients with advanced MPM overall and specifically in elderly and poor performance status (PS) patients. Methods Retrospective chart review was performed for all patients with histologically confirmed MPM seen at University Health Network/Princess Margaret Cancer Centre (UHN-PM). Results A total of 667 patients with MPM were identified and 304 advanced-disease MPM (aMPM) patients had continuing care at U HN- P M (UP-cohort). In the UP-cohort, 77% of patients received ≥ one line of systemic treatment. Systemic therapy trial participation was 39%. Patients not treated with systemic therapy (29%) were more likely to be ≥ 75 years and PS ≥ 2. Median OS was 15.3 months (95%CI 13.6-18.3), with longer survival in treated vs. untreated patients (17.4 vs. 10.6 months; P = .01). Longer survival with systemic treatment was seen in patients ≥75 years (12.7 vs. 6.6 months) and patients with poor PS (9.1 vs. 5.9 months). Median progression-free-survival (PFS) and OS for patients treated with second-line therapy was poor (3.0 and 8.9 months, respectively). Discussion In our real-world analysis of patients with aMPM treated at an academic referral centre, systemic treatment was given to the majority of patients and benefit was seen even in the elderly and poor PS patients frequently underrepresented in clinical trials. Trial participation was potentially facilitated by the formation of a dedicated multidisciplinary MPM clinic.

OBJECTIVE Schwann cells (SCs) have been shown to play an essential role in axon regeneration in both peripheral nerve injuries (PNIs) and spinal cord injuries (SCIs). The transplantation of SCs as an adjunctive therapy is currently under investigation in human clinical trials due to their regenerative capacity. Therefore, a reliable method for procuring large quantities of SCs from peripheral nerves is necessary. This paper presents a well-developed, validated, and optimized manufacturing protocol for clinical-grade SCs that are compliant with Current Good Manufacturing Practices (CGMPs). METHODS The authors evaluated the SC culture manufacturing data from 18 clinical trial participants who were recruited for autologous SC transplantation due to subacute SCI (n = 7), chronic SCI (n = 8), or PNIs (n = 3). To initiate autologous SC cultures, a mean nerve length of 11.8 ± 3.7 cm was harvested either from the sural nerve alone (n = 17) or with the sciatic nerve (n = 1). The nerves were digested with enzymes and SCs were isolated and further expanded in multiple passages to meet the dose requirements for transplantation. RESULTS An average yield of 87.2 ± 89.2 million cells at P2 and 150.9 ± 129.9 million cells at P3 with high viability and purity was produced. Cell counts and rates of expansion increased with each subsequent passage from P0 to P3, with the largest rate of expansion between P2 and P3. Larger harvest nerve lengths correlated significantly with greater yields at P0 and P1 (p < 0.05). In addition, a viability and purity above 90% was sustained throughout all passages in nearly all cell products. CONCLUSIONS This study presents reliable CGMP-compliant manufacturing methods for autologous SC products that are suitable for regenerative treatment of patients with SCI, PNI, or other conditions.

Demand for dynamic random access memory (DRAM) bandwidth has outpaced DRAM transistor performance. Given the options of major process investment to scale beyond sixth-generation graphics double-data-rate (GDDR6) or replace GDDR6 with costly high bandwidth memory (HBM), this article presents a solution that simultaneously increases pin and energy efficiency through the integration of four-level pulse amplitude modulation (PAM-4) into the single-ended memory interface. Building upon the existing GDDR6 architecture, evolutionary modifications to input, output, clocking, and data path, along with the component package design, enable a per-pin data rate of more than 22 Gb/s.

BACKGROUND: Patients with recurrent glioblastoma (GBM) are often treated with antiangiogenic agents, such as bevacizumab (BEV). Despite therapeutic promise, conventional MRI methods fail to help determine which patients may not benefit from this treatment. PURPOSE: To use MR spectroscopic imaging (MRSI) with intermediate and short echo time to measure corrected myo-inositol (mI)normalized by contralateral creatine (hereafter, mI/c-Cr) in participants with recurrent GBM treated with BEV and to investigate whether such measurements can help predict survivorship before BEV initiation (baseline) and at 1 day, 4 weeks, and 8 weeks thereafter. MATERIALS AND METHODS: In this prospective longitudinal study (2016–2020), spectroscopic data on mI—a glial marker and osmoregulator within the brain—normalized by contralateral creatine in the intratumoral, contralateral, and peritumoral volumes of patients with recurrent GBM were evaluated. Area under the receiver operating characteristic curve (AUC) was calculated for all volumes at baseline and 1 day, 4 weeks, and 8 weeks after treatment to determine the ability of mI/c-Cr to help predict survivorship. RESULTS: Twenty-one participants (median age ± standard deviation, 62 years ± 12; 15 men) were evaluated. Lower mI/c-Cr in the tumor before and during BEV treatment was predictive of poor survivorship, with receiver operating characteristic analyses showing an AUC of 0.75 at baseline, 0.87 at 1 day after treatment, and 1 at 8 weeks after. A similar result was observed in contralateral normal-appearing tissue and the peritumoral volume, with shorter-term survivors having lower levels of mI/c-Cr. In the contralateral volume, a lower ratio of mI to creatine (hereafter, mI/Cr) predicted shorter-term survival at baseline and all other time points. Within the peritumoral volume, lower mI/c-Cr levels were predictive of shorter-term survival at baseline (AUC, 0.80), at 1 day after treatment (AUC, 0.93), and at 4 weeks after treatment (AUC, 0.68). CONCLUSION: Lower levels of myo-inositol normalized by contralateral creatine within intratumoral, contralateral, and peritumoral volumes were predictive of poor survivorship and antiangiogenic treatment failure as early as before bevacizumab treatment. Adapting MR spectroscopic imaging alongside conventional MRI modalities conveys critical information regarding the biologic characteristics of tumors to help better treat individuals with recurrent glioblastoma. Clinical trial registration no. NCT02843230 © RSNA, 2021 Online supplemental material is available for this article.

Recent estimates have reiterated that non-fatal causes of disease, such as low back pain, headaches and depressive disorders, are amongst the leading causes of disability-adjusted life years (DALYs). For these causes, the contribution of years lived with disability (YLD) – put simply, ill-health – is what drives DALYs, not mortality. Being able to monitor trends in YLD closely is particularly relevant for countries that sit high on the socio-demographic spectrum of development, as it contributes more than half of all DALYs. There is a paucity of data on how the population-level occurrence of disease is distributed according to severity, and as such, the majority of global and national efforts in monitoring YLD lack the ability to differentiate changes in severity across time and location. This raises uncertainties in interpreting these findings without triangulation with other relevant data sources. Our commentary aims to bring this issue to the forefront for users of burden of disease estimates, as its impact is often easily overlooked as part of the fundamental process of generating DALY estimates. Moreover, the wider health harms of the COVID-19 pandemic have underlined the likelihood of latent and delayed demand in accessing vital health and care services that will ultimately lead to exacerbated disease severity and health outcomes. This places increased importance on attempts to be able to differentiate by both the occurrence and severity of disease.

ZusammenfassungModerne perioperative Behandlungskonzepte legen großen Wert auf eine aktive Rolle der Patienten. Um dies zu ermöglichen, ist eine intensive Patientenbegleitung notwendig. Aus dieser Notwendigkeit heraus hat sich die Position der ERAS®-Nurse entwickelt. Sie ist der primäre Ansprechpartner für den Patienten vor, während und nach der Operation. Die konzeptionelle Erstellung und fortwährende Weiterentwicklung eines ERAS-Konzeptes mag vor allem ärztliche Tätigkeit sein, die tagtägliche Arbeit am Patienten und die Füllung des Konzeptes mit Leben wird jedoch vor allem durch eine ERAS-Nurse bewerkstelligt. Ihre Hauptaufgaben liegen in der präoperativen Patientenaufklärung, der täglichen Visitation der Patienten während des stationären Aufenthaltes, dem Ausfüllen der Dokumentation, der fortwährenden Kommunikation mit Pflegekräften und dem Monitoring der Einhaltung der ERAS-Vorgaben aller beteiligten Teammitglieder. Entsprechend wichtig ist es, die Position der ERAS-Nurse zu schaffen und sie als wertiges Mitglied ins Team zu integrieren. Im folgenden Artikel, der auf unseren Erfahrungen als zertifiziertes ERAS-Zentrum beruht, wird das Berufsbild umfänglich vorgestellt, einschl. Aufgaben, Bedeutung und Lösungsvorschlägen für gängige Probleme.

Standard treatment options in classic HCL (cHCL) result in high response rates and near normal life expectancy. However, the disease itself and the recommended standard treatment are associated with profound and prolonged immunosuppression, increasing susceptibility to infections and the risk for a severe course of COVID-19. The Hairy Cell Leukemia Foundation (HCLF) has recently convened experts and discussed different clinical strategies for the management of these patients. The new recommendations adapt the 2017 consensus for the diagnosis and management with cHCL to the current COVID-19 pandemic. They underline the option of active surveillance in patients with low but stable blood counts, consider the use of targeted and non-immunosuppressive agents as first-line treatment for cHCL, and give recommendations on preventive measures against COVID-19.

With the development of modern EUS, multiple imaging functions, transducer settings, and examination modes have become available for clinical settings. While the major determinants of the ultrasound beam are still comprised of the signal wavelength, its frequency range, and its amplitude, other modifications and calculations have gained more interest for advanced users, such as tissue harmonic imaging (THI), spatial and frequency compounding, certain versions of speckle reduction, and various Doppler/duplex settings. The goal of such techniques is a better, perhaps more realistic image, with reduced artifacts (such as speckle), better image contrast, and an improved signal-to-noise ratio. In addition, 'add-ons' such as THI, which is based on the phenomenon of nonlinear distortion of acoustic signals as they travel through tissues, provide greater contrast and an enhanced spatial resolution than conventional EUS. Finally, optimization of spectral and color Doppler imaging in EUS requires experience and knowledge about the basic principles of Doppler/duplex phenomena. For these purposes, factors such as adjustment of Doppler controls, Doppler angle, color gain, spectral wall filters, and others require special attention during EUS examinations. Incorporating these advanced techniques in EUS examinations may be time-consuming and cumbersome. Hence, practical guidelines enabling endosonographers to steer safely through the large quantity of technological properties and settings (knobology) are appreciated. This review provides an overview of the role of important imaging features to be adjusted before, during, and after EUS procedures.

ZusammenfassungZur Behandlung der chronischen Hepatitis C wurden in den letzten Jahren direkt wirkende antivirale Medikamente (DAA) zugelassen und sind bei Erwachsenen etabliert. Sie machten die interferonbasierten Therapien obsolet. Auch für Kinder und Jugendliche stehen seit Kurzem einige DAA zur Verfügung, die überwiegend ab dem Alter von 3 Jahren eingesetzt werden können.Die chronische Hepatitis C wird bei Kindern überwiegend vertikal übertragen und ist selten. Sie ist zwar zunächst eine wenig aktive und progrediente Erkrankung, kann aber im Erwachsenenalter in eine Leberzirrhose mit der Folge eines hepatozellulären Karzinoms übergehen. Die Diagnose ist mit der Bestimmung des Anti-HCV (IgM/IgG) und der HCV-RNA im Serum mit Genotypisierung leicht zu stellen. Die DAA werden oral appliziert und ausgesprochen gut toleriert. Drei Wirkstoffkombinationen stehen aktuell zur Verfügung, und 2021 wird eine weitere zugelassen. Die Heilungschancen sind mit über 95 % ausgesprochen gut und anhaltend.Im eigenen Krankengut wurden 25 Jungen und Mädchen überwiegend mit Genotyp 1 im Alter von 4 bis 17 Jahren mit DAA behandelt. Unabhängig von der Höhe der HCV-RNA im Serum waren alle bereits nach 4 Wochen HCV-RNA negativ und erzielten einen dauerhaften Erfolg.Die wesentliche Aufgabe ist nun, alle Kinder und Jugendlichen mit einer chronischen Hepatitis C zu identifizieren. Bei der äußerst guten Heilungschance kann davon ausgegangen werden, dass das Eradikationsziel in dieser Altersgruppe in absehbarer Zeit erreicht werden kann.

Background There is clear evidence that tic disorders (TDs) are associated with psychosocial stress as well as emotional and behavioral problems. Studies have shown that individuals with TDs have higher acute physiological stress responses to external, single stressors (as reflected by saliva cortisol). The aim of the present study was to examine a physiological marker of longer-term stress (as reflected by hair cortisol concentration) in children and adolescents with TDs and unaffected siblings of individuals with TDs. Methods Two samples of a European cohort were included in this study. In the COURSE sample, 412 children and adolescents aged 3–16 years with a chronic TD including Tourette syndrome according to DSM IV-TR criteria were included. The ONSET sample included 131 3–10 years old siblings of individuals with TDs, who themselves had no tics. Differences in hair cortisol concentration (HCC) between the two samples were examined. Within the COURSE sample, relations of HCC with tic severity and perceived psychosocial stress as well as potential effects and interaction effects of comorbid emotional and behavioral problems and psychotropic medication on HCC were investigated. Results There were no differences in HCC between the two samples. In participants with TDs, there were no associations between HCC and tic severity or perceived psychosocial stress. No main effects of sex, psychotropic medication status and comorbid emotional and behavioral problems on HCC were found in participants with TDs. Conclusion A link between HCC and TDs is not supported by the present results.

Clinically relevant myopenia accompanies spinal cord injury (SCI), and compromises function, metabolism, body composition, and health. Myostatin, a transforming growth factor (TGF)β family member, is a key negative regulator of skeletal muscle mass. We investigated inhibition of myostatin signaling using systemic delivery of a highly selective monoclonal antibody - muSRK-015P (40 mg/kg) - that blocks release of active growth factor from the latent form of myostatin. Adult female mice (C57BL/6) were subjected to a severe SCI (65 kdyn) at T9 and were then immediately and 1 week later administered test articles: muSRK-015P (40 mg/kg) or control (vehicle or IgG). A sham control group (laminectomy only) was included. At euthanasia, (2 weeks post-SCI) muSRK-015P preserved whole body lean mass and sublesional gastrocnemius and soleus mass. muSRK-015P-treated mice with SCI also had significantly attenuated myofiber atrophy, lipid infiltration, and loss of slow-oxidative phenotype in soleus muscle. These outcomes were accompanied by significantly improved sublesional motor function and muscle force production at 1 and 2 weeks post-SCI. At 2 weeks post-SCI, lean mass was significantly decreased in SCI-IgG mice, but was not different in SCI-muSRK-015P mice than in sham controls. Total energy expenditure (kCal/day) at 2 weeks post-SCI was lower in SCI-immunoglobulin (Ig)G mice, but not different in SCI-muSRK-015P mice than in sham controls. We conclude that in a randomized, blinded, and controlled study in mice, myostatin inhibition using muSRK-015P had broad effects on physical, metabolic, and functional outcomes when compared with IgG control treated SCI animals. These findings may identify a useful, targeted therapeutic strategy for treating post-SCI myopenia and related sequelae in humans.

Many environmental chemicals are being identified as suspected neurotoxicants based on the findings of both experimental and epidemiological studies. Organophosphate esters (OPEs), which are among the chemicals that have replaced neurotoxic polybrominated diphenyl ethers (PBDEs) after 2004, have also become an important public health topic as evidence regarding their potential for early-life neurotoxicity is growing. In 233 mother child pairs from Cincinnati, OH, we measured concentrations of the OPE metabolites bis(1,3-dichloro-2-propyl) phosphate (BDCIPP), bis-2-chloroethyl phosphate (BCEP), diphenyl phosphate (DPHP), and di-n-butyl phosphate (DNBP) in the urine of pregnant women at 16 and 26 weeks gestation and at delivery. At age 8 years, we assessed children's cognition using the Wechsler Intelligence Scale for Children-IV. In models adjusted for maternal race, income, body mass index, and IQ, maternal urinary BCEP was associated with a modest increase in child full-scale IQ (ß: 0.81 per a ln-unit BCEP increase; 95 % CI: 0.00, 1.61) while other OPEs were not associated with changes in full-scale IQ or any IQ subscales. Maternal serum PBDE concentrations did not confound the relationships between urinary OPE metabolites and child IQ. Using Bayesian kernel machine regression, we did not find that concentrations of a mixture of OPE metabolites during gestation was associated with any child cognition measures. The results of this study are not consistent with other published work, and a larger sample size would be beneficial to explore potential associations more fully. Therefore, additional studies are necessary to continue studying prenatal OPE exposure and child neurodevelopment and behavior.

Background Systems of care that improve mental health and substance use disorder Screening, Brief Intervention and Referral to Treatment (SBIRT) for pregnant and postpartum women are needed. Aims The aim of this study is to determine if women receiving prenatal care from January 2020 to April 2021 are more likely to be screened, screen positive, be referred for treatment and attend treatment with technology facilitated SBIRT, compared to women receiving prenatal care and in‐person SBIRT January 2017 to December 2019. Materials & Methods Technology facilitated SBIRT, designated Listening to Women (LTW), includes text message‐based screening, phone‐based brief intervention, and referral to treatment by a remote care coordinator. A total of 3535 pregnant and postpartum women were included in the quasi‐experimental study and data were collected via text message and Electronic Health Record. Results In‐person SBIRT was completed by 65.2% (1947/2988) of women while 98.9% (547/553) of women approached agreed to take part in LTW and 71.9% (393/547) completed SBIRT via LTW. After controlling for potentially confounding variables, women enrolled in LTW were significantly more likely to be screened (relative risk [RR]: 1.10, 95% CI 1.03–1.16), screen positive (RR 1.91, 95% CI 1.72–2.10), referred to treatment (RR 1.55, 95% CI 1.43–1.69) and receive treatment (RR 4.95, 95% CI 3.93–6.23), compared to women receiving in‐person SBIRT. Black women enrolled in LTW were significantly more likely to screen positive (RR 1.65, 95% CI 1.35–2.01), be referred to treatment (RR 1.54, 95% CI 1.35–1.76) and attend treatment (RR 5.49, 95% CI 3.69–8.17), compared to Black women receiving in‐person SBIRT. Discussion LTW appears to increase the proportion of pregnant and postpartum women receiving key elements of SBIRT.

This paper considers off-grid microgrids (MGs) from the Philippine archipelago and analyses their energy generation in differents aspects. Seven different energy clusters are used, representing realistic configurations and renewable energy shares. A Robust Model Predictive Control (MPC) framework is used for the energy management and coordination task of these island MGs. The MPC is based on a min./max. optimization procedure, which takes into account the whole uncertainty set. The reliability of the MG operations are analysed with respect to the different clusters; this evaluation is conducted using μ-analysis, performed with respect to the baseline model and the uncertainty set. The demand-side compliance of the MG is also investigated, with respect to stochastic behaviours of the demands and of the renewable sources (wind and solar). Numerical simulation results are presented in order to demonstrate that reliable power outlets are produced despite variation in renewables and of the demands. This paper offers a thorough analysis of simple energy system coordinated via MPC, showing how this method can indeed be used for renewable MG management, offering robustness and ensuring reliability.

The incidence and mortality rates of pancreatic cancer (PC) are increasing. It is important to discriminate PC from the other pancreatic lesions; however, differential diagnosis based on conventional transabdominal ultrasound (US) remains challenging even though US is often the first examination performed. Transabdominal contrast-enhanced ultrasound (CEUS) has high diagnostic accuracy for PC. This meta-analysis aimed to examine the utility of low-mechanical-index CEUS with enhancement for PC diagnosis. A systematic meta-analysis of all potentially relevant articles was performed. Fixed-effects or random-effects models were used to investigate pooled sensitivity, specificity, positive likelihood ratio (LR) and negative LR. The study enrolled 983 patients from nine eligible studies. The pooled estimates of sensitivity and specificity were 92% (95% confidence interval [CI]: 0.89-0.94) and 76% (95% CI: 0.71-0.81), respectively. The diagnostic odds ratio (DOR) for CEUS was high (53.62). The area under the summary receiver operating characteristic curve was 0.95. Funnel plots revealed no publication bias, and there was no significant relationship between the DORs and study characteristics, including continent, type of contrast agent, contrast agent dosage and scan phase. Only number of patients affected diagnostic ability. This meta-analysis indicates that CEUS with enhancement pattern is useful for diagnosis of PC.

Background : Growing teratoma syndrome is defined as conversion of a metastatic immature tumor to a mature tumor after adjuvant chemotherapy and remains an area of investigation because of its unclear pathogenesis. Because of its risk of malignant transformation, the primary treatment strategy for pediatric patients is surgical resection. Case : In this report we present a case of a pediatric patient with recurrent growing teratoma syndrome who was treated with chemotherapy, debulking procedures, and cryoablation for the growing nodules throughout her abdominal cavity. The patient has had a good clinical outcome without recurrent malignant tumor. Summary and Conclusion : These masses do not always regress with chemotherapy and complete surgical excision or ablation should be attempted when possible.

The purpose of the data assimilation is to use all the available information to determine as accurately as possible the state of the atmosphere. In this context we consider the assimilation of the GPS-ZTD (Global Positioning System – Zenith Total Delay) by a nudging scheme in Regional Atmospheric Modeling System at Institute of Atmospheric Sciences and Climate (RAMS@ISAC) at medium horizontal resolution (5 km). The water vapour mixing ratio ( q v ) given by the RAMS@ISAC is perturbed according to the differences between observed and simulated ZTD. To verify the impact of the GPS-ZTD data assimilation on the representation of the atmospheric humidity field, especially at the local scale, a numerical experiment was performed over central Italy area, over a one-month time frame. The studied network consists of 41 geodetic receivers and 3 single frequency receivers, this latter category of receivers has turned up more and more in marketing for the very low cost with respect to high level of performance. For what concerns all devices, processing was carried out in PPP (Precise Point Positioning) using goGPS, an Open Source Program Package for GNSS Positioning. For the application of PPP processing to single-frequency receivers, goSEID method (an alternative implementation of the SEID approach integrated in the goGPS open source software) was applied; the algorithm, starting from the observations of a unique (or more) dual frequency “reference” receiver, is able to generate L2 synthetic observations for any single frequency receiver located in its surroundings (15–20 km). Results show that the assimilation of GPS-ZTD has a positive impact on the simulation of the Integrated Water Vapour over the areas where GPS receivers are located. The results obtained, using data assimilation, were indeed compared with those obtained by the model without data assimilation of GPS-ZTD. The two outputs were subsequently evaluated against observations obtained from two geodetic receivers (ROUN and INGR) not used in the assimilation process. The result showed that the independent observation was more consistent with the model output in which also the single-frequency receivers had been assimilated. The assimilation of GPS-ZTD improves also the simulated precipitation, especially by reducing false alarms.

Introduction The VACTERL association is a rare malformation complex, showing at least three anomalies of the following organ systems: vertebra, anorectum, heart and vessels, trachea and esophagus, genitourinary tract, and limbs. In addition to a multifactorial event, congenital vascular disorders are also discussed as triggers for the VACTERL association. The aim of this study was to determine whether there is a genetic background for vascular disorders triggering VACTERL association. Materials and Methods We performed a functional analysis on whole exome sequencing data of 21 patients with VACTERL or VACTERL-like phenotype using the online analysis tool “Database for Annotation, Visualization and Integrated Discovery (DAVID) v6.8.” The study was approved by the institutional ethics committee (approval no. 026–13). Written informed consent was obtained from all patients or their parents. Results We identified a total of 86 genetic variants (in 75 genes) classified as damaging (including probably damaging missense, nonsense, and frameshift variants), which are associated to cardiovascular development. Each investigated patient showed at least one damaging variant in genes associated to cardiovascular development. These variants were further reduced by significance in cardiovascular development to 39 genetic variants (in 33 genes). Of note, a pair of siblings, both presenting with cardiac and renal defects, had the same damaging variant in two different genes. Conclusion Our results indicate a genetic background for congenital vascular disorders in patients with VACTERL association. In line with the literature, our data suggest that genetic mutation led to vascular diseases, which in turn may cause malformations similar to the VACTERL association.

ZusammenfassungDas Budd-Chiari-Syndrom ist eine seltene vaskuläre Erkrankung, die durch eine Obstruktion des hepatischen venösen Abflusses gekennzeichnet ist. Ätiologisch spielen diverse Erkrankungen, die eine Gerinnungsstörung verursachen, wie beispielsweise myeloproliferative Erkrankungen eine Rolle. Der akute Gefäßverschluss kann zu einer akuten Phlebitis mit Fieber und der klassischen Trias des akuten Leberversagens aus Aszites, Hepatomegalie und abdominellen Schmerzen führen. Allerdings kommen auch subakute Verlaufsformen vor. Aufgrund der wechselnden Symptomatik und Ausprägung, abhängig vom zeitlichen Verlauf und dem Ausmaß der betroffenen Gefäße, gestaltet sich eine Diagnose oft schwierig. Die Sonografie als ubiquitär verfügbares und kosteneffizientes diagnostisches Mittel spielt dabei eine führende Rolle. Mithilfe der Doppler-Sonografie lässt sich zusätzlich die Hämodynamik visualisieren. Beim akuten thrombotischen Verschluss lassen sich die betroffenen Lebervenen meist nicht oder nur teilweise darstellen. Bei nicht okkludierenden Thromben können turbulente Flussmuster im Bereich der venösen Abflussstörung entstehen, im Bereich der Stenose ist die Flussgeschwindigkeit dann erhöht. Die Kontrastmittelsonografie bietet hinsichtlich einer Diagnosestellung eine höhere Spezifität als die Dopplersonografie. Durch die Computertomografie (CT) und Magnetresonanztomografie (MRT) können Thromben beziehungsweise die Ursache für eine Obstruktion teilweise direkt visualisiert werden. Sobald die Diagnose gesichert ist, muss eine Antikoagulation eingeleitet werden, aber auch eine Therapie des zugrunde liegenden Krankheitsbildes begonnen werden. Reichen symptomkontrollierende Maßnahmen nicht aus, kann eine Angioplastie/ein Stenting zur Wiedereröffnung kurzstreckiger Stenosen oder eine Transjuguläre intrahepatische portosystemische Shunt-Anlage (TIPSS) erwogen werden. Als Ultima Ratio bleibt die Lebertransplantation. Die kontroverse Studienlage zur Präzision der diagnostischen Methoden und Charakteristika der Bildgebung werden in diesem Review anhand zahlreicher Fallbeschreibungen zusammengefasst.

Objective Advanced age is associated with a higher risk of both pain and dementia, with many studies finding that dementia often heightens sensitivity to pain. Vascular dementia (VaD) is the second most common type of dementia. Only a few observational or retrospective studies have examined pain responsiveness in VaD, suggesting that it could increase pain unpleasantness (i.e., pain affect). This study compared thermal pain psychophysics between a cohort of patients with VaD and healthy control (HC) subjects. Design Single-center, cross-sectional, between-subjects design. Subjects Verbally communicative patients with probable VaD (n = 23) and age- and sex-matched HCs (n = 23). Methods A thermal psychophysics protocol assessed “mild pain” and “moderate pain” thresholds (temperature in degrees Celsius) and associated unpleasantness ratings (0–20 scale) in both the VaD and HC groups. Psychophysics were compared between groups by way of a mixed-effects analysis, controlling for depressive symptoms. Results There were no significant differences between groups for pain thresholds (main effect P = 0.086, Cohen’s d: mild = 0.55, moderate = 0.27). However, unpleasantness ratings were higher in the VaD group than in the HC group (main effect P = 0.003; mild pain P = 0.022, Cohen’s d = 0.79; moderate pain P = 0.057, Cohen’s d = 0.6). Conclusions These results are consistent with prior observational findings suggesting that VaD could make patients more susceptible to pain, particularly its affective component.

VEGF inhibition in gastric cancer has a proven benefit in the second line setting. Pazopanib, an oral tyrosine kinase inhibitor, selectively inhibits VEGFR-1, -2 and -3, c-kit and PDGF-R resulting in inhibition of angiogenesis. This open-label randomized phase II trial (2:1) investigated the efficacy of combining pazopanib with FLO (5-fluorouracil, oxaliplatin) vs FLO alone (internal control arm) as first-line treatment in patients with advanced adenocarcinoma of the stomach and gastroesophageal junction (GEJ). Eighty-seven patients were randomized and 78 patients were eligible and evaluable (PaFLO arm 51 patients, FLO arm 27 patients). The PFS rate at 6 months (primary endpoint) was 34% in the PaFLO arm vs 30% in the FLO arm. Comparing PaFLO with FLO median PFS was 4.66 months (95% confidence interval [CI] 2.87-6.46) vs 4.47 months (95% CI 1.79-7.14) (95% CI, hazard ratio [HR] 0.96 (0.60-1.55), P = .882 [exploratory]); median OS was 10.19 months (95% CI 5.46-14.92) vs 7.33 months (95% CI 4.93-9.73), (95% CI HR 1.01 [0.62-1.65], P = .953, exploratory), disease control rate was 72% vs 59%. PaFLO was well tolerable, toxicities were slightly higher in the PaFLO arm. Major adverse events were loss of appetite, nausea, fatigue, diarrhea, neutropenia and thrombocytopenia. Adding pazopanib to chemotherapy shows signs of efficacy but no major improvement in this randomized phase 2 trial. The PFS at 6 months in both arms was lower than expected from the literature. Biomarkers identifying subgroups who benefit and novel combinations are needed. ClinicalTrials.gov: NCT01503372.

To prevent diseases, efforts are needed to determine how to address Adverse Childhood Experiences (ACEs), including parenting behaviors. The objective of this study, conducted in Nashville TN in 2017, was to initiate testing the psychometric properties of two new Adverse Childhood Experiences (ACEs) screening tools, the Quick Parenting Assessment (QPA) and Other Childhood Stressors (OCS). In a clinic serving low-income families, caregivers of children ages 2-10 completed assessments of parenting (QPA), other stressors (OCS), child behavior problems ((Strength and Difficulties Questionnaire (SDQ)), and Attitudes Toward Spanking (ATS). The QPA takes 1 min to complete and assesses for healthy and unhealthy parenting behaviors. Seventy-five percent of eligible participants completed the survey (N=558). A reduced 10-item QPA yielded a Cronbach's alpha of 0.79 and, in 4-10-year-olds, was associated with high SDQ conduct, hyperactivity, and total difficulties scores (r=0.44, 0.48, and 0.47; all p 4 were nine times more likely than those children with scores of ≤2 to have behavior problems (OR=8.93, 95% CI = 3.74-21.32). Elevated QPAs were associated with the ATS (r=0.47, p < .001). The OCS was also associated with high SDQ total difficulties scores (r=0.28, p< 0.001). Two pediatric ACEs screening tools, the QPA and the OCS, have promising psychometric properties. The findings suggest that parenting behaviors may play an outsized role in the pathogenesis of outcomes associated with ACEs. We discuss the clinical application of QPA at our institution and the theoretical potential for this instrument to reduce the rates of short- and long-term health problems.

ZusammenfassungDie histologische Sicherung von Tumoren ist zusammen mit einem adäquaten Staging die Voraussetzung für eine stadiengerechte und personalisierte Therapie. Beschrieben werden Indikationen, technische Möglichkeiten und Einschränkungen sowie potenzielle Komplikationen der bildgebend geführten Nadelbiopsie mittels Ultraschalls (US), Computertomografie (CT) und Endosonografie (EUS). Welches Verfahren für welches Organ und welche Läsion?

Infektiöse fokale Leberläsionen (FLL) treten in der klinischen Praxis häufig auf, wobei bakterielle Leberabszesse die Hälfte ausmachen. Eine genaue Diagnose der FLL ist für die Auswahl der am besten geeigneten Therapie und zur Vorbeugung von Komplikationen unerlässlich. Ziel der aktuellen Arbeit ist es, den Nutzen von Ultraschall und kontrastmittelverstärktem Ultraschall (CEUS) zur Erkennung und Charakterisierung infektiöser Leberläsionen zu beschreiben.Infective focal liver lesions (FLL) are commonly encountered in clinical practice, with bacterial hepatic abscesses accounting for half of the visceral abscesses diagnosed. Accurate diagnosis of suspected hepatic infections is imperative for selecting the most appropriate therapy and preventing complications. The current review aims to update on the use of ultrasound and contrast-enhanced ultrasound (CEUS) to detect and characterize infective liver lesions.

The ongoing climate change and increasingly strict climate goals of the European Union demand decisive action in all sectors. Especially in manufacturing industry, demand response measures have a high potential to balance the industrial electricity consumption with the increasingly volatile electricity supply from renewable sources. This work aims to develop a method to forecast the electrical energy demand of metal cutting machine tools as a necessary input for implementing demand response measures in factories. Building on the results of a previous study, long short-term memory networks (LSTM) and convolutional neural networks (CNN) are examined in their performance for forecasting the electric load of a machine tool for a 100 second time horizon. The results show that especially the combination of CNN and LSTM in a deep learning approach generates accurate and robust time series forecasts with reduced feature preparation effort. To further improve the forecasting accuracy, different network architectures including an attention mechanism for the LSTMs and different hyperparameter combinations are evaluated. The results are validated on real production data obtained in the ETA Research Factory.

BACKGROUND Genetics of sudden cardiac deaths (SCD) remains frequently undetected. Genetic analysis is recommended in undefined selected cases in the 2021 ERC-guideline. The emergency medical service and physicians (EMS) may play a pivotal role for unraveling SCD by saving biomaterial for later molecular autopsy. Since for high-throughput DNA-sequencing (NGS) high quality genomic DNA is needed. We investigated in a prospective proof-of-concept study the role of the EMS for the identification of genetic forms of SCDs in the young. METHODS We included patients aged 1-50 years with need for cardiopulmonary resuscitation attempts (CPR). Cases with non-natural deaths were excluded. In two German counties with 562,904 residents 39,506 services were analysed. Paired end panel-sequencing was performed, and variants were classified according to guidelines of the American College of Medical Genetics (ACMG). RESULTS 769 CPR-attempts were recorded (1.95% of all EMS-services; CPR-incidence 68/100,000). In 103 cases CPR were performed in patients