Search

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.]

Background: Trauma is a major public health issue and has an extensive burden on the health system in South Africa. Many trauma scoring systems have been developed to estimate trauma severity and predict mortality. The prediction of mortality between different trauma scoring systems have not been compared at district-level health facilities in South Africa. The objective was to compare four trauma scoring systems (injury severity score (ISS), revised trauma score (RTS), Kampala trauma score (KTS), trauma and injury severity score (TRISS)) in predicting mortality in trauma-related patients presenting to a district-level hospital in Cape Town. Methods: A retrospective analysis of all trauma patients managed in the resuscitation unit of Khayelitsha Hospital during a six-month period. Logistic regression was done, and empirical cut of points used to maximise sensitivity and specificity on receiver operating characteristic curves. The outcome was all-cause in-hospital mortality. Results: In total, 868 participants were analysed after 50 were excluded due to missing data. The mean (± SD) age was 28±11 years, 726 (83.6%) were males, and penetrating injuries (n = 492,56.6%) dominated. The mortality rate was 5.2% (n = 45). TRISS was the best mortality predictor (c-statistic 0.93, sensitivity 90%, specificity 87%). All scoring systems had overlapping confidence intervals. Conclusion: TRISS, ISS, RTS and KTS performed equivocally in predicting mortality in trauma-related patients managed at a district-level facility. The appropriate scoring system should be the simplest one which can be practically implemented and will likely differ between facilities.

Summary: A 16-year-old male presented with a 2-year history of a 5 x 5 cm dermatofibrosarcoma protuberans (DFSP) on the medial aspect of his right lower leg. Wide local excision (WLE) with a 2cm margin was performed and a free anterolateral thigh (ALT) flap was used to reconstruct the defect. This technique satisfactorily reconstructed a large defect in an adolescent with minimal donor site morbidity, as the donor site was closed primarily, and a functionally and aesthetically acceptable outcome. There was no evidence of tumour recurrence at 6 months follow-up.

Graft-versus-host disease (GVHD) remains the leading cause of nonrelapse mortality after allogeneic stem cell transplantation for hematological malignancies. Manifestations of GVHD in the central nervous system (CNS) present as neurocognitive dysfunction in up to 60% of patients; however, the mechanisms driving chronic GVHD (cGVHD) in the CNS are yet to be elucidated. Our studies of murine cGVHD revealed behavioral deficits associated with broad neuroinflammation and persistent Ifng upregulation. By flow cytometry, we observed a proportional shift in the donor-derived T-cell population in the cGVHD brain from early CD8 dominance to later CD4 sequestration. RNA sequencing of the hippocampus identified perturbations to structural and functional synapse-related gene expression, together with the upregulation of genes associated with interferon-γ responses and antigen presentation. Neuroinflammation in the cortex of mice and humans during acute GVHD was recently shown to be mediated by resident microglia-derived tumor necrosis factor. In contrast, infiltration of proinflammatory major histocompatibility complex (MHC) class II+ donor bone marrow (BM)–derived macrophages (BMDMs) was identified as a distinguishing feature of CNS cGVHD. Donor BMDMs, which composed up to 50% of the CNS myeloid population, exhibited a transcriptional signature distinct from resident microglia. Recipients of MHC class II knockout BM grafts exhibited attenuated neuroinflammation and behavior comparable to controls, suggestive of a critical role of donor BMDM MHC class II expression in CNS cGVHD. Our identification of disease mediators distinct from those in the acute phase indicates the necessity to pursue alternative therapeutic targets for late-stage neurological manifestations.

Over the years, a diverse range of drawdown measures has evolved to guide asset management. We show that almost all of these measures fit into a unified framework. This new framework simplifies the implementation of drawdown measures and improves understanding their similarities and differences. Conceptual differences between drawdown measures translate into different rankings of portfolios, which we document in a simulation study. Our research also shows that all drawdown measures can (to some degree) discriminate between skillful and unskillful portfolio managers, but differ in terms of accuracy. However, the ability to detect skill does not easily improve performance ratios where drawdown measures serve as the denominator. In conclusion, our study shows that the choice of an adequate drawdown measure is vital to the assessment of investments because different measures emphasize different aspects of risk.

Background : Around 20% - 30% of depressed individuals experience a chronic form of depression lasting two or more years. This naturalistic study investigates the characteristics and the course of chronic depressed patients (CD) during standard antidepressant treatment in comparison to not chronically depressed (NCD) patients. Methods : Data of 954 patients were drawn from the prospective naturalistic, multicenter study of the German research network on depression, CD was met as classifier by 113 patients (11.8%), whereas 841 patients (88.2%) had non-chronic courses (NCD). Results : CD was significantly associated with a low age at onset, use of benzodiazepines, psychotherapy at baseline, substance abuse, a depressive personality disorder and a low degree of extraversion. CD patients showed a longer hospital stay, lower remission rates, increased rates of suicidal ideation as well as higher depression scores at discharge. In addition, individuals with chronic depression continued to obtain higher neuroticism scores and lower extraversion scores at discharge. Limitation : Results were assessed by a post-hoc analysis, based on prospectively collected data. Conclusion : CD patients have an inferior outcome in clinical measures as well as personality dimensions (i.e. low extraversion) compared to non-CD patients. These findings support the notion that CD patients entering a setting of standard psychiatric inpatient care will show less benefit compared to non-CD patients, and that this difference as such may be used as a stratifying marker for providing specialized psychiatric treatment with optimized pharmacological and psychotherapeutic protocols.

CD8+ cytotoxic T-lymphocytes are essential components of the anti-tumor immunity. To better understand the expansion of CD8+ T-cells we used multiplex fluorescence immunohistochemistry to study Ki67+CD8+ cells in normal lymphoid tissues, selected inflammatory diseases and cancers in 41 large sections/ microenvironment tissue microarrays (TMAs) as well as 765 samples in a conventional TMA format. The evaluation of more than 20 different compartments of normal lymphoid tissues revealed that the percentage of proliferating (ki67+) CD8+ cells did commonly not exceed 3%. In inflammations, the percentage of Ki67+CD8+ cells was more variable and higher compared to normal tissues. In cancers, the percentage of Ki67+CD8+ cells was higher in the tumor center than at the invasive margin. In the tumor center of 765 colorectal cancers, the density of Ki67+CD8+ cells and the percentage of proliferating CD8+ cytotoxic T-cells was significantly associated with microsatellite instability (p

Objectives: To determine the appropriateness and understanding of the revised, draft South African Paediatric Food-Based Dietary Guidelines (SA-PFBDG) among siSwati speaking mothers/caregivers of children aged 0–36 months. Previous exposure to guidelines with similar messages, barriers and enablers to following the guidelines were also assessed. Design: A descriptive, cross-sectional qualitative research approach was followed. Purposive and snowball sampling were used to recruit a total of 75 participants. Data were collected by means of focus-group discussions from 12 groups. Setting: Kabokweni, Mpumalanga, South Africa. Subjects: The study population included mothers/caregivers older than 18 years who provided informed consent. Results: The participants were generally aware of messages similar to those contained in the revised, draft SA-PFBDG. They reported exposure to these messages at clinics/hospitals, radio/television, and the Road-to-Health booklet. Participants showed good understanding of guidelines on breastfeeding, complementary feeding, inclusion of protein-rich and starchy foods as well as fruit and vegetables in the diets of young children as well as hygiene practices. The guidelines on avoiding tea, coffee and sugar drinks and high-sugar, high-fat salty snacks, being active and providing five small meals were less well understood. Enablers to following the guidelines were its perceived importance and positive impact on children’s health. Barriers included misinterpretation of the guidelines and lack of money and resources. Conclusion: The revised, draft SA-PFBDGs are appropriate for the age group 0–36 months. A degree of rewording is suggested to aid understanding. The guidelines can be used as an educational tool to improve the nutritional status of children in South Africa.

Background: This paper provides an overview of a series of studies undertaken to assess the appropriateness and understanding of the revised, draft South African Paediatric Food-Based Dietary Guidelines (SA-PFBDGs) amongst mothers/ caregivers of children aged 0–5 years. Previous exposure to guidelines with similar messages, barriers and enablers to following the guidelines were also assessed. Design: Qualitative methods were used to collect data from 38 focus-group discussions (isiXhosa = 11, Afrikaans = 11, English =10 and siSwati = 6) resulting in 268 participants. Setting: Breede Valley sub-district (Worcester), Stellenbosch Municipality (Stellenbosch, Pniel and Franschhoek) and Northern Metropole (Atlantis, Witsand, Du Noon and Blouberg), City of Cape Town, Western Cape province, as well as Ehlanzeni District (Kabokweni) in Mpumalanga province. Subjects: Mothers/caregivers older than 18 years who provided informed consent to participate. Results: The majority of participants had previous exposure to guidelines with similar messages to the SA-PFBDGs. Information sources included nurses, local clinics, family, friends and media. Possible barriers to following the guidelines included limited physical and financial access to resources; cultural/family practices, poor social support and time constraints. Outdated information, misconceptions, inconsistent messages and contrasting beliefs were evident. The vocabulary of some messages was not well understood. Education on infant and young child feeding and visual portrayal of the guidelines could aid understanding. Conclusion: A degree of rewording should be considered for improved understanding of the revised, draft SA-PFBDGs. Once adopted, the guidelines can be used to educate various stakeholders, including parents, caregivers, healthcare providers and educators, on the correct nutritional advice for children aged 0–5 years ensuring the healthy growth and development of young children in South Africa.

This chapter discusses the importance of Machine Learning and Deep Learning, two methodologies which have gained importance due to the impact of Digital Transformation and the increasing growth of data sets to Big Data generated through the Internet connectivity. Machine Learning is a subset of Artificial Intelligence used to create algorithms which can modify itself without human intervention to generate a desired output. Deep Learning is also a sub-set of Artificial Intelligence used to create algorithms and functions similar to those in Machine Learning, but there are numerous layers of these algorithms which provide different interpretation to the data it feeds on. Machine Learning and Deep Learning methods can be used for computer system or network analysis in case of cyber threat intrusion incidents detection. This is essential to prevent intrusion of malicious code and to enhance cybersecurity.

AIMS Interventions to decrease readmissions in psychiatric patients are urgently needed. In Switzerland therapeutic leave (TL) composes a cornerstone of inpatient treatment. TL is a planned time-limited absence from the inpatient ward giving patients the opportunity to test their resilience in their usual environment. Evidence of its applicability as an intervention reducing readmissions is lacking. Therefore, our objective was to examine the association between TL and readmission risk. METHODS Using the Kaplan-Meier curve we compared the time to readmission of 3'302 inpatients at the UPK Basel with and without TL. Cox regression was applied, integrating other covariates associated with readmission. RESULTS The Kaplan-Meier curve indicated longer cumulative survival in patients with TL. The log-rank test implied statistical significance (χ2(1) = 18.8, p

Introduction Several drugs of abuse (DOA) are capable of modulating neurohypophysial hormones, such as oxytocin (OT) and vasopressin (VP), potentially resulting in the development of psychological abnormalities, such as cognitive dysfunction, psychoses, and affective disorders. Efavirenz (EFV), widely used in Africa and globally to treat HIV, induces diverse neuropsychiatric side effects while its abuse has become a global concern. The actions of EFV may involve neurohypophysial system (NS) disruption like that of known DOA. This study investigated whether sub-chronic EFV exposure, at a previously-determined rewarding dose, alters peripheral OT and VP levels versus that of a control, ∆9-tetrahydrocannabinol (∆9-THC), methamphetamine (MA) and cocaine. Materials and methods To simulate the conditions under which reward-driven behavior had previously been established for EFV, male Sprague Dawley rats (n = 16/exposure) received intraperitoneal vehicle (control) or drug administration across an alternating sixteen-day dosing protocol. Control administration (saline/olive oil; 0.2 ml) occurred on odd-numbered and drug administration (EFV: 5 mg/kg, ∆9-THC: 0.75 mg/kg, MA: 1 mg/kg, or cocaine: 20 mg/kg) on even-numbered days followed by euthanasia, trunk blood collection and plasma extraction for neuropeptide assay. Effect of drug exposure on peripheral OT and VP levels was assessed versus controls and quantified using specific ELISA kits. Statistical significance was determined by Kruskal-Wallis ANOVA, with p, Highlights • Efavirenz alters rat plasma neuropeptide levels in a similar manner to illicit drugs. • Opposed to cocaine, methamphetamine reduces plasma vasopressin rather than oxytocin. • Efavirenz and ∆−9-tetrahydrocannabinol comparably affect peripheral neuropeptides. • Efavirenz reduces vasopressin more than oxytocin versus ∆−9-tetrahydrocannabinol.

Background NF1-mutated tumours represent a small subset (10–15%) of melanomas, not sufficiently analysed in large clinical cohorts. This study investigated the largest multicentre collection of NF1-mutated melanomas to date. Methods This study analysed a multicentre tumour tissue sample cohort from 266 patients with NF1-mutated melanoma. Targeted next-generation sequencing of the TERT promoter and 29 relevant melanoma genes was performed. Survival was compared with NF1 wild-type cohorts from the Tissue Registry in Melanoma project (n = 432). Results Most NF1-mutated melanoma arose in the head-and-neck region of patients >60 years. NF1 alterations were frequently inactivating, primarily non-sense, less frequently truncating mutations. Non-inactivating NF1 mutations more frequently co-occurred with activating BRAF and RAS mutations. NF1-mutated tumours had higher numbers of gene mutations and UV signature C>T and CC>TT transitions than BRAF, RAS and triple wild-type melanomas. NF1-mutated acral and mucosal melanomas harboured a different mutation signature and were frequent in women (69% and 83%, respectively), differing from non-acral cutaneous NF1-mutated melanomas (men 73%, women 27%). Overall survival in stage IV disease was comparable for patients with NF1-mutated or wild-type melanoma. However, in patients receiving first-line immune checkpoint inhibitor treatment, better median overall survival (mOS) was observed for NF1-mutated than wild-type tumours (mOS = not reached vs mOS = 25.82, p = 0.0154, n = 80 and 432, respectively). Conclusions Cutaneous, acral and mucosal NF1-mutated melanomas vary in clinical and genetic characteristics and demonstrate a favourable outcome on immune checkpoint inhibition therapy.

Stroke is one of the most common neurological emergencies and requires rapid detection and treatment (time is brain). There is still insufficient knowledge about stroke warning signs. It is therefore of crucial importance that trained personnel in the preclinical setting recognize the relevant warning symptoms and collect the necessary information to quickly refer the patient to the appropriate additional care structure. For this purpose, training of the emergency medical services (EMS) and the correct triage are of particular importance. The on-site assessment of a patient with a suspected stroke by EMS should include airway, breathing, vital functions, a basic neurological examination, blood glucose testing and cardiac monitoring.Patients with suspected acute ischemic stroke should be brought to the nearest hospital with a stroke unit, ideally connected with a tertiary stroke centre. From there, once the primary diagnosis has been carried out and appropriate therapy initiated, the patient can be transferred to a thrombectomy center if necessary. To improve supply times, teleradiological networking plays a major role both between clinics of different levels of care and in communication between pre- and intra-hospital care providers. Also, the use of mobile stroke units can improve preclinical stroke care and reduce delays in access to intravenous thrombolytic therapy and mechanical thrombectomy. The identification of preclinical biomarkers could also save time.

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?

To assess patient perspective and professional practice of intraarticular therapies (IATs) across Europe, an expert international multidisciplinary panel designed two open web-based surveys: one targeting people who had experienced at least two IATs (44 items); and one targeting health care providers (HCPs) (160 items). Surveys were disseminated via patient and professional associations and social media. A descriptive analysis was performed. The surveys were answered by 200 patients and 186 HCPs from 26 countries, showing that IAT is routinely performed by rheumatologists (97%) and orthopaedic surgeons (89%), with specific training being compulsory in a few countries. The most frequent indications for IAT are arthritis (76%), osteoarthritis (74%), crystal arthritis (71%) and bursitis (70%); the most frequently injected joints are knee (78%) and shoulder (70%); and the most used compounds are glucocorticoids. The majority of HCPs report informing patients about side-effects (73%), benefits (72%), and the nature of the procedure (72%), which coincides with 27% of patients reporting that they had not been informed about benefits or potential complications of IATs; 73% of patients had not been asked whether they wanted an anaesthetic. Few HCPs (10%) obtain written consent (56% get oral consent, being mandatory for 32%), a procedure deemed necessary by 41% of the patients. 50% of patients reported a clear benefit of IAT and 20% experienced complications including pain, impaired mobility, rashes, or swelling. In summary, the practice of IAT is variable across Europe, and although patients perceive it as relatively safe and usually effective procedure, some gaps were identified.

There is an accumulation of blast injuries on New Year's Eve due to fireworks.During an attempt to manufacture a firework the substances being mixed in a mortar exploded. The left hand of the patient was severely injured.During the operative treatment with radical debridement and generous amputation without osteosynthesis, a basic hand function according to Entin could initially be preserved; however, at a later stage the fourth finger could not be preserved, so that a prosthesis became necessary.This case report shows the importance of expertise in hand surgery in the treatment of such severe injuries. A toe-to-hand transplantation represents an additional treatment option.

Mucin 5AC (MUC5AC) is a secreted gel-forming mucin expressed by several epithelia. In the colon, MUC5AC is expressed in scattered normal epithelial cells but can be abundant in colorectal cancers. To clarify the relationship of MUC5AC expression with parameters of tumor aggressiveness and mismatch repair deficiency (dMMR) in colorectal cancer, a tissue microarray containing 1812 colorectal cancers was analyzed by immunohistochemistry. MUC5AC expression was found in 261 (15.7%) of 1,667 analyzable colorectal cancers. MUC5AC expression strongly depended on the tumor location and gradually decreased from proximal (27.4% of cecum cancers) to distal (10.6% of rectal cancers; p p p

Schuttelfrost und systemische Infektzeichen fuhren einen Patienten ins Krankenhaus. Ursachlich fur seinen produktiven Husten und Hamoptysen ist bei dem Raucher eine Lobarpneumonie. Ein unerwarteter Befund in der Blutkultur macht eine weitere Diagnostik bei dem Schrittmachertrager umgehend erforderlich.

Background The short- and long-term prognosis of Takotsubo syndrome (TTS) presenting with right ventricular (RV) involvement remains poorly understood. Research Question What is the incidence and clinical outcome of RV involvement in TTS? Study Design and Methods This study analyzed 839 consecutive patients with TTS (758 female subjects and 81 male subjects) in a multicenter registry. RV involvement was defined as wall motion abnormality of the RV free wall, with or without apical involvement. The median long-term follow-up was 2.1 years (interquartile range, 0.3-4.5 years). The primary outcome was in-hospital and out-of-hospital all-cause mortality. The secondary end point was a composite of in-hospital death, thromboembolic events, cardiogenic shock, pulmonary edema, and malignant arrhythmias. Results The incidence of RV involvement in TTS was 11% (n = 93). More often patients with RV involvement were male compared with patients without RV involvement (P = .02). There was a slight difference in the left ventricular ejection fraction measured in patients with RV involvement vs those patients with isolated left ventricular TTS (38 ± 10% vs 40 ± 10%; P = .03). No major differences in terms of comorbidities were observed between groups except regarding a history of cancer, which was significantly more prevalent in patients with TTS presenting with RV involvement (P = .03). Physical stressors were more prevalent in the RV group (P Interpretation RV involvement defines a high-risk cohort of patients with TTS. Clinical Trial Registration ClinicalTrials.gov ; No.: NCT04361994 ; URL: www.clinicaltrials.gov .

Augmented-Reality-basierte digitale Assistenzsysteme werden bereits erfolgreich im industriellen Kontext eingesetzt, um die Arbeitskräfte bei manuellen Tätigkeiten zu unterstützen. Die Nutzung in der additiven Fertigung wurde allerdings noch nicht umfassend untersucht. Angelehnt an das klassische Technologiemanagement wurde ein methodisches Vorgehen entwickelt, um anwendungsspezifische Use Cases für die Additive Fertigung zu adaptieren.

Purpose of review Multiple myeloma is a disease of elderly adults. Improvement in survival has occurred because of biological insights and novel agents. Therapeutic options involve choices today, thus have become more complex. Demographics have led to an increased number of elderly patients and age may be associated with a poorer outcome but is not the only prognostic predictor today. Recent findings To evaluate patients’ health status rather than their chronological age alone, frailty scores and functional geriatric assessments are used to identify prognostic groups, avoid adverse events, compare clinical trials and tailor treatment. As most clinical trials exclude frail elderly patients, those enrolled therein are often younger and healthier than the typical multiple myeloma patient. This represents a challenge for frail cohorts because of their increased risk of adverse events, overtreatment and undertreatment and/or therapy discontinuation, which may lead to poorer survival and quality of life (QoL). Reassessing patients’ status via geriatric assessments is also relevant during treatment to adjust interventions appropriately. Summary Integrating geriatric assessments may lead to individual treatment decisions, dose adjustments, better clinical outcome and QoL. Prospective clinical trials that enroll elderly multiple myeloma patients with comorbidities, incorporate frailty scores/geriatric assessments and help with prognostication, adverse event avoidance and QoL maintenance, remain warranted.

Os Registros de Câncer de Base Populacional (RCBP) são sistemas de informação em câncer que coletam dados sobre todos os casos novos de câncer de uma área geográfica definida, através de um processo contínuo e sistemático de coleta. São úteis para a vigilância epidemiológica, no acompanhamento de grupos ocupacionais específicos ou coortes de indivíduos expostos a agentes cancerígenos e para o planejamento de políticas públicas e avaliação de serviços de saúde. Neste texto, utilizaramse dados do Registro de Câncer de Base Populacional de São Paulo para exemplificar algumas informações úteis para o planejamento e gestão no município de São Paulo.

AIM: Psychotropic drugs like opioids and benzodiazepines are prescribed for traumas resulting from road traffic crashes and the risk of developing an addiction deserves consideration. This study aims to shed light on how the consumption of those drugs evolves over time among older road traffic injury (RTI) victims. METHODS: We conducted a nationwide Swedish register-based longitudinal study to identify trajectories of post-RTI psychotropic drug use. All individuals aged 50 years and older who had a hospital visit for an RTI from 2007 to 2015 were followed up during a two-year period; those who used the drugs prior to the RTI were excluded. Trajectories were identified by performing latent class trajectory analysis on drug dispensation data for opioids and benzodiazepines separately (66,034 and 66,859 adults, respectively, in total). RESULTS: Three trajectories were identified for opioids and four for benzodiazepines. The largest group in both instances included people with no-use/minimal use throughout the follow-up (81.3% and 92.8%). "Sporadic users" were more frequent among users of opioids (16.7%) than benzodiazepines (4.3%), whereas "chronic users" were found in similar proportions (2.0% and 1.8%). "Delayed chronic use" characterized the fourth group of benzodiazepine users (1.0%). CONCLUSION: Several trajectories of psychotropic drug use were identified after RTI, from limited to chronic. Although chronic use was uncommon, a better understanding of the factors likely to increase that risk is warranted given the seriousness of the problem.

Background Mastocytosis encompasses a heterogeneous group of disorders characterized by accumulation of clonal mast cells (MCs) in the skin and/or internal organs. Patients typically present with a broad variety of recurrent mediator-related clinical symptoms, including severe anaphylaxis. However, not all patients with mastocytosis experience anaphylactic reactions. Objective We sought to identify disease-specific biomarkers in plasma that could be used to predict patients with mastocytosis with increased risk of anaphylaxis. Methods Nineteen patients (≥18 years) and 2 control groups (11 subjects with allergic asthma and 13 healthy volunteers without history of atopy) were recruited. In total, 248 plasma proteins were analyzed by Proximity Extension Assay using Olink Proseek Multiplex panels. Results We identified 4 novel proteins, in addition to tryptase, E-selectin, adrenomedullin, T-cell immunoglobulin, and mucin domain 1, and CUB domain–containing protein 1/CD138 to be significantly increased in patients with mastocytosis compared with both patients with asthma and healthy controls. Furthermore, we investigated whether we could discriminate between patients with mastocytosis with or without anaphylaxis. In addition to tryptase, we identified 3 novel proteins, that is, allergin-1, pregnancy-associated plasma protein-A, and galectin-3, with significantly different levels in patients with mastocytosis with anaphylaxis compared with those without anaphylaxis. Conclusions Newly identified proteomic biomarkers may be used to predict patients with mastocytosis with increased risk of anaphylaxis.

In general, governments and health authorities have taken precautions during the COVID-19 pandemic to reduce the viral spread and protect vulnerable citizens. Patients with multiple myeloma (MM) have an increased risk of being infected with COVID-19 and developing a fatal course due to the related immunodeficiency. We investigated how Danish patients with MM reported their quality of life (QoL) pre-COVID and during COVID, in an ongoing longitudinal QoL survey. The responses given during the first and second wave of the COVID-19 pandemic were pooled, analyzed and compared to the same period the year before. We hypothesized that locking down the society would have caused deteriorated QoL and that patients living alone and those under the age of 65 would be particularly affected by the situation. Surprisingly, our study showed the opposite. Statistically significant and clinically relevant differences were primarily found during the first lock down and represented reduced fatigue, improved role functioning, decreased insomnia and improved physical health summaries in patients below 65 years of age. These results indicate that Danish patients with MM might have felt protected and safe by COVID restrictions. Otherwise, the questionaries used in QoL-MM survey may not have been able to capture the impact of the COVID-19 pandemic. Importantly, this indicates that QoL survey data obtained in clinical studies, in countries with highly developed health-care systems using standard questionnaires during the pandemic, allow room for interpretation without being adjusted for the impacts of the pandemic. In general, governments and health authorities have taken precautions during the COVID-19 pandemic to reduce the viral spread and protect vulnerable citizens. Patients with multiple myeloma (MM) have an increased risk of being infected with COVID-19 and developing a fatal course due to the related immunodeficiency. We investigated how Danish patients with MM reported their quality of life (QoL) pre-COVID and during COVID, in an ongoing longitudinal QoL survey. The responses given during the first and second wave of the COVID-19 pandemic were pooled, analyzed and compared to the same period the year before. We hypothesized that locking down the society would have caused deteriorated QoL and that patients living alone and those under the age of 65 would be particularly affected by the situation. Surprisingly, our study showed the opposite. Statistically significant and clinically relevant differences were primarily found during the first lock down and represented reduced fatigue, improved role functioning, decreased insomnia and improved physical health summaries in patients below 65 years of age. These results indicate that Danish patients with MM might have felt protected and safe by COVID restrictions. Otherwise, the questionaries used in QoL-MM survey may not have been able to capture the impact of the COVID-19 pandemic. Importantly, this indicates that QoL survey data obtained in clinical studies, in countries with highly developed health-care systems using standard questionnaires during the pandemic, allow room for interpretation without being adjusted for the impacts of the pandemic.

Erenumab is a monoclonal antibody, targeted against the calcitonin gene-related peptide (CGRP) receptor. Clinical studies have demonstrated prophylactic efficacy in both episodic (EM) and chronic migraine (CM). The aim of the present study is to evaluate the efficacy of treatment in tertiary headache centers under real-life conditions. In a retrospective analysis, the period of 3 months before and after initiation of erenumab therapy was compared. Relevant parameters (headache days, headache intensity, headache duration, acute medication, previous prophylaxis treatments) were collected from medical charts of all migraine patients (N = 82) who started treatment with erenumab between November 1st 2018 and May 1st 2019 at two tertiary headache centers in Germany. The sample included 68 female (82.9%) and 14 male patients aged between 22 and 78 years (mean 51.1 years, SD 10.5 years). Of these patients, 57.3% met the criteria for CM and 56.9% overused acute medication. Under therapy with erenumab, a significant reduction of headache days was observed from the first month on. The effect was most pronounced in the third month with a decrease in monthly headache days from 16.6 to 11.6 days (p p = 0.004) and average duration of headache attacks (p = 0.016). The 50% responder rate in patients with CM was lower in the first month compared to EM but then increased similarly to EM. Patients with medication overuse (MO) also responded to the therapy. There was a reduction in medication overuse from 57% at baseline to 29% after therapy (p = 0.011). Overall, a positive result of treatment with erenumab can be shown in a highly selected sample with severely affected migraine patients and a refractory course prior to treatment. This re-confirms the clinical trial data also for this highly selected group.

Background Unlike other non-steroidal anti-inflammatory drugs, indomethacin has been shown to be highly effective in two forms of trigeminal autonomic cephalalgias, hemicrania continua and paroxysmal hemicrania and in some forms of idiopathic stabbing headaches. This specificity is unique in the headache field. Previous findings suggest the involvement of the trigeminal autonomic reflex to play an important role in the pathophysiology of these diseases. Methods 22 healthy participants were enrolled in a double-blind, three-day within-subject design. The participants received indomethacin, ibuprofen or placebo in a randomized order. After an incubation period of 65 min the baseline lacrimation and the lacrimation during intranasal stimulation evoked by kinetic oscillation stimulation were assessed using Schirmer II lacrimation tests. The lacrimation difference in mm was calculated and compared in a repeated measures ANOVA. Results No significant differences were found between the three conditions. Conclusion In our study, neither indomethacin nor ibuprofen had an inhibitory effect on the trigeminal autonomic reflex. We suggest that blocking this reflex may not be the treatment mechanism of indomethacin.

INTRODUCTION: The aim of the study was to investigate whether robotic-assisted surgery is associated with lower incremental resource use amongst obese patients relative to non-obese patients after a Danish nationwide adoption of robotic-assisted surgery in women with early-stage endometrial cancer. This is a population-based cohort study based on registers and clinical data.MATERIAL AND METHODS: All women who underwent surgery (robotic, laparoscopic, and laparotomy) from 2008 to 2015 were included and divided according to body mass index (RESULTS: In total, 3934 women were included. The adoption of robotic-assisted surgery did not demonstrate statistically significant implications for total costs among obese women (€3417; 95% confidence interval [CI] -€854 to €7688, P = .117). Further, for obese women, a statistically significant reduction in bed days related to the index hospitalization was demonstrated (-1.9 bed days; CI -3.6 to -0.2, P = .025). For non-obese women, the adoption of robotic-assisted surgery was, however, associated with statistically significant total costs increments of €9333 (95% CI €3729 to €14936, P = .001) and no reduction in bed days related to the index hospitalization was observed (+0.9 bed days; 95% CI -0.6 to 2.3, P = .242).CONCLUSIONS: The national investment in robotic-assisted surgery for endometrial cancer seems to have more modest cost implications post-surgery for obese women. This may be partly driven by a significant reduction in bed days related to the index hospitalization among obese women, as well as reductions in subsequent hospitalizations.

In this study, we investigate the effect of sexual assault on sexual function in adult women. Participants consisted of 136 women recruited from the Emergency Clinic for Rape Victims in Stockholm. Seventy-three women returned for follow-up six months after the assault and completed the Female Sexual Function Index, assessing their current sexual function compared to that before the assault. A majority (44/73) reported impaired function, which was associated with a simultaneous diagnosis of PTSD (OR 5.7; 95% CI 1.7-19.1

The aim of this animal study was to investigate the effect of platelet-rich plasma (PRP) injections into the temporomandibular joint (TMJ) to treat antigen-induced arthritis AIA. AIA was induced via the application of bovine serum albumin (BSA) into the TMJ. Clear histological signs and protein analysis results indicating inflammation of the TMJ were observed. Afterwards, two PRP injections were performed over an interval of 2 weeks. Concentration levels of the proinflammatory cytokines IL-1β (PRP: 33.7 ± 5.6 pg/mg, untreated: 50.0 ± 2.9 pg/mg; p = 0.04) and TNF-α (PRP: 20.7 ± 2.5 pg/mg, untreated: 31.4 ± 2.7 pg/mg; p = 0.03) were significantly decreased in the PRP-treated joints. A significant reduction in signs of histological inflammation, such as hyperplasia of the synovial membrane, leucocyte infiltration, cartilage surface alterations, and an increase in cartilage-specific glycosaminoglycan content, was observed. This animal study supports the understanding of the underlying effects of PRP treatment in the TMJ, and may enhance novel PRP therapies in the future.

Background The aim of this study was to validate whether regional ventilation and perfusion data measured by electrical impedance tomography (EIT) with saline bolus could discriminate three broad acute respiratory failure (ARF) etiologies. Methods Perfusion image was generated from EIT-based impedance–time curves caused by 10 ml 10% NaCl injection during a respiratory hold. Ventilation image was captured before the breath holding period under regular mechanical ventilation. DeadSpace%, Shunt% and VQMatch% were calculated based on lung perfusion and ventilation images. Ventilation and perfusion maps were divided into four cross-quadrants (lower left and right, upper left and right). Regional distribution defects of each quadrant were scored as 0 (distribution% ≥ 15%), 1 (15% > distribution% ≥ 10%) and 2 (distribution% DefectV, DefectQ and DefectV+Q) were the sum of four cross-quadrants of the corresponding images. Results A total of 108 ICU patients were prospectively included: 93 with ARF and 15 without as a control. PaO2/FiO2 was significantly correlated with VQMatch% (r = 0.324, P = 0.001). Three broad etiologies of ARF were identified based on clinical judgment: pulmonary embolism-related disease (PED, n = 14); diffuse lung involvement disease (DLD, n = 21) and focal lung involvement disease (FLD, n = 58). The PED group had a significantly higher DeadSpace% [40(24)% vs. 14(15)%, PED group vs. the rest of the subjects; median(interquartile range); P DefectQ score than the other groups [1(1) vs. 0(1), PED vs. the rest; P DefectV+Q score than the PED and FLD groups [0(1) vs. 2.5(2) vs. 3(3), DLD vs. PED vs. FLD; P DefectV score than the other groups [2(2) vs. 0(1), FLD vs. the rest; P DeadSpace% to identify PED was 0.894 in all ARF patients. The AUC for using the DefectV+Q score to identify DLD was 0.893. The AUC for using the DefectV score to identify FLD was 0.832. Conclusions Our study showed that it was feasible to characterize three broad etiologies of ARF with EIT-based regional ventilation and perfusion. Further study is required to validate clinical applicability of this method. Trial registration clinicaltrials, NCT04081142. Registered 9 September 2019—retrospectively registered, https://clinicaltrials.gov/show/NCT04081142.

Objective To standardize and assess the reliability of ultrasonographic assessment of inflammatory and structural lesions in patients with hand osteoarthritis (OA). Methods The Outcome Measures in Rheumatology Ultrasound Working Group selected synovial hypertrophy (SH), joint effusion (JE), and power Doppler (PD) signals as the main inflammatory lesions in hand OA, and suggested osteophytes in the scapho-trapezio-trapezoid (STT) and cartilage defects in the proximal interphalangeal (PIP) joints as novel additions to previous structural scoring systems. A complementary imaging atlas provided detailed examples of the scores. A reliability exercise of static images was performed for the inflammatory features, followed by a patient-based exercise with 6 sonographers testing inflammatory and structural features in 12 hand OA patients. We used Cohen's kappa for intrareader and Light's kappa for interreader reliability for all features except PD, in which prevalence-adjusted bias-adjusted kappa (PABAK) was applied. Percentage agreement was also assessed. Results The web-based reliability exercise demonstrated substantial intra- and interreader reliability for all inflammatory features (kappa > 0.64). In the patient-based exercise, intra- and interreader reliability, respectively, varied: SH kappa = 0.73 and 0.45; JE kappa = 0.70 and 0.55; PD PABAK = 0.90 and 0.88; PIP joint cartilage kappa = 0.56 and 0.45; and STT osteophytes kappa = 0.62 and 0.36. Percentage close agreement was high for all features (>85%). Conclusion With ultrasound, substantial to excellent intrareader reliability was found for inflammatory features of hand OA. Interreader reliability was moderate, but overall high close agreement between readers suggests that better reliability is achievable after further training. Assessment of osteophytes in the STT joint and cartilage in the PIP joints achieved less reliability and the latter is not endorsed.

Secreted frizzled-related protein 4 (SFRP4) controls WNT signaling and is thought to play a role for tumor aggressiveness. Here, we analyzed a tissue microarray containing 11,152 prostate cancers with pathological, clinical and molecular data by immunohistochemistry. SFRP4 expression was higher in cancer than in non-neoplastic acinar cells. SFRP4 staining was seen in 64.9% of tumors and classified as weak in 33.2%, moderate in 23.9% and strong in 7.8% of cancers. SFRP4 overexpression was linked to advanced tumor stage, high classical/quantitative Gleason grade (p

Background TFAP2D is a transcription factor important for modulating gene expression in embryogenesis. Its expression and prognostic role in prostate cancer has not been evaluated. Methods Therefore, a tissue microarray containing 17,747 prostate cancer specimens with associated pathological, clinical, and molecular data was analyzed by immunohistochemistry to assess the role of TFAP2D. Results TFAP2D expression was typically increased in prostate cancer as compared to adjacent non-neoplastic glands. TFAP2D staining was considered negative in 24.3% and positive in 75.7% of 13,545 interpretable cancers. TFAP2D staining was significantly linked to advanced tumor stage, high classical and quantitative Gleason grade, lymph node metastasis, and a positive surgical margin (p ≤ 0.0045). TFAP2D positivity was more common in ERG fusion positive (88.7%) than in ERG negative cancers (66.8%; p TMPRSS2:ERG fusion revealed that associations with tumor phenotype and patient outcome were largely driven by the subset of ERG negative tumors. Multivariate analysis did not identify TFAP2D protein expression levels as a robust independent prognostic parameter. Positive TFAP2D immunostaining was significantly associated with 10 of 11 previously analyzed chromosomal deletions in ERG negative cancers (p ≤ 0.0244 each) indicating that elevated TFAP2D expression parallels genomic instability in prostate cancer. Conclusion These data demonstrate that TFAP2D protein overexpression is linked to prostate cancer progression and genomic instability in ERG negative prostate cancers.

Scientific reports 10, 2373 (2020). doi:10.1038/s41598-020-58761-6, Published by Macmillan Publishers Limited, part of Springer Nature, [London]

Survivin is an inhibitor of apoptosis. Aberrant survivin expression occurs in malignant tumors and has often been linked to unfavorable patient outcome. Here we analyzed 12 432 prostate cancers by immunohistochemistry. Survivin immunostaining was regularly expressed at high levels in normal prostate epithelium but expression was often reduced in prostate cancers. Among 9492 evaluable prostate cancers, 9% expressed survivin strongly, 19% moderately, 28% weakly, and 44% lacked it. Loss of cytoplasmic survivin was seen in advanced tumor stage, higher Gleason score, preoperative PSA levels, and Ki‐67 labeling index, and associated with earlier PSA recurrence (P, Survivin encoded by the BIRC5 gene was analyzed by immunochemistry on a tissue microarray of 12 432 prostate cancers. We found loss of survivin expression linked to early PSA recurrence in patients treated with radical prostatectomy. Loss of survivin expression showed a moderate and independent impact on PSA recurrence‐free survival. This effect remained also in PTEN‐deleted cancers.

Background and purpose — Few studies have reported the mortality rate after skeletal fractures involving different locations, within the same population. We analyzed the 30-day and 1-year mortality rates following different fractures. Patients and methods — We included 295,713 fractures encountered in patients 16–108 years of age, registered in the Swedish Fracture Register (SFR) from 2012 to 2018. Mortality rates were obtained by linkage of the SFR to the Swedish Tax Agency population register. The standardized mortality ratios (SMR) at 30 days and 1 year were calculated for fractures in any location and for each of 27 fracture locations, using age- and sex-life tables from Statistics Sweden (www.scb.se). Results — The overall SMR at 30 days was 6.8 (95% CI 6.7–7.0) and at 1 year 2.2 (CI 2.2–2.2). The SMR was > 2 for 19/27 and 13/27 of the fracture locations at 30 days and 1 year, respectively. Humerus, femur, and tibial diaphysis fractures were all associated with high SMR, at both 30 days and 1 year. Interpretation — Patients sustaining a fracture had approximately a 7-fold increased mortality at 30 days and over 2-fold increased mortality at 1 year as compared with what would be expected in the general population. High mortality rates were seen for patients with axial skeletal and proximal extremity fractures, indicating frailty in these patient groups.

AIMS Giant cell tumour of bone (GCTB) is histologically defined as a lesion containing reactive giant cells and a neoplastic mononuclear cell population; in up to 92% of cases, GCTB is characterised by a specific mutation of the histone gene H3F3A. The cellular composition ranges from giant-cell-rich to giant-cell-poor. The diagnosis of GCTB can be challenging, and several other lesions need to be excluded, e.g. aneurysmal bone cysts, non-ossifying fibromas, chondroblastomas, brown tumours, and giant-cell-rich osteosarcomas. Our aim was to analyse the clinical history, imaging, molecular pathology and histology of three H3F3A-mutated bone tumours without detectable giant cells. None of the patients received denosumab therapy. METHODS AND RESULTS Diagnostic material was obtained by curettage or resection and/or biopsy. Common histomorphological features of all three reported lesions were fibrocytic, oval cells in a background of osteoid and an absence of multinuclear giant cells as confirmed with CD68 immunohistochemistry. We used immunohistochemistry and Sanger sequencing to demonstrate positivity for the H3.3 p.G34W mutation. Differential diagnoses were systematically excluded on the basis of histomorphology, immunohistochemistry, and fluorescence in-situ hybridisation. The imaging (radiography, computed tomography, and magnetic resonance imaging) for all three cases is presented and discussed. CONCLUSIONS We believe that these GCTBs without giant cells expand one end of the heterogeneous range of GCTB. Because of the lack of giant cells, correct diagnosis of GCTB is challenging or even impossible on histological grounds alone. In these cases, detection of the characteristic H3F3A mutation (G34W-specific antibody RM263 or sequencing) is extremely helpful for diagnosing those lesions without giant cells as giant cell tumours of bone.

Contains fulltext : 219395.pdf (Publisher’s version ) (Closed access) Extensive research has been done on how social media have changed democratic society, politics, and public opinion. Social media are often regarded as a mirror of the public that, during political events, provides journalists and academics with a clear image of what position the public has on political issues and which sub-issues it uses to back it up. Yet, there is strong empirical evidence that active Twitter users differ in terms of background characteristics from the electorate, and that the most influential users possess specific traits. However, this does not necessarily mean that the opinions expressed on Twitter cannot reflect public opinion. This study aims to compare sub-issues used on Twitter to polled public opinion data in the context of the 2016 so-called Ukraine referendum’ in the Netherlands. Our main findings indicate that there is a remarkable resemblance between the two domains in terms of sub-issues used and prominence of these sub-issues. Yet, this is mostly the case when not taking duplicates or retweets into account. Overall, the Twitter debate showed to be less nuanced than the polled public opinion data, as fewer sub-issues appeared. 20 p.

The aim of the study was to investigate the use of serial measurements of TSH-receptor autoantibodies (TRAb) with the newest available assay technology to predict the course of Graves’ Orbitopathy (GO) during the first 24 months from disease onset. Serial serum samples from patients with GO (103 mild/135 severe) were collected between 2007 and 2017 and retrospectively analyzed. The course of GO were classified into mild/severe 12 months after manifestation (severe: NOSPECS≥5; mild

Evidence suggests that selective serotonin reuptake inhibitors (SSRIs) reorganize neural networks via a transient window of neuroplasticity. While previous findings support an effect of SSRIs on intrinsic functional connectivity, little is known regarding the influence of SSRI-administration on connectivity during sequence motor learning. To investigate this, we administered 20 mg escitalopram or placebo for 1-week to 60 healthy female participants undergoing concurrent functional magnetic resonance imaging and sequence motor training in a double-blind randomized controlled design. We assessed task-modulated functional connectivity with a psycho-physiological interaction (PPI) analysis in the thalamus, putamen, cerebellum, dorsal premotor, primary motor, supplementary motor, and dorsolateral prefrontal cortices. Comparing an implicit sequence learning condition to a control learning condition, we observed decreased connectivity between the thalamus and bilateral motor regions after 7 days of escitalopram intake. Additionally, we observed a negative correlation between plasma escitalopram levels and PPI connectivity changes, with higher escitalopram levels being associated with greater thalamo-cortico decreases. Our results suggest that escitalopram enhances network-level processing efficiency during sequence motor learning, despite no changes in behaviour. Future studies in more diverse samples, however, with quantitative imaging of neurochemical markers of excitation and inhibition, are necessary to further assess neural responses to escitalopram.

Interstitial lung disease (ILD) is one of the most relevant extra-articular manifestations of rheumatic diseases resulting in a substantial increase in morbidity and mortality. Early diagnosis and close monitoring to identify patients at high risk of progression are crucial to establish the need for targeted treatment with immunomodulatory and antifibrotic drugs, with potential ability to change the course of the disease. However, there are unmet needs in this field as pulmonary auscultation, chest radiography, or pulmonary function studies do not allow identification of the most incipient stages of the disease. High-resolution computed tomography (HRCT), which is the current gold standard for diagnosis and evolutionary control, is problematic owing to ionizing radiation, cost, and accessibility. In this context, lung ultrasound (LUS) is an attractive tool in a growing research and validation process. The identification of vertical artifacts, such as B lines, and alterations of the pleural line present a good correlation with the presence of ILD by HRCT and have a good concordance with the extent and severity of the disease, with sensitivity and negative predictive values of up to 100%. Regarding the monitoring of the evolution, the validation process of LUS is in a more preliminary phase but data is encouraging. All this, together with its safety, accessibility, low cost, and good patient acceptance, postulate LUS as a useful tool for the screening of ILD and for the optimization of the indications of HRCT. Key Points • The good sensitivity and negative predictive values of LUS postulate this technique as a useful tool for the screening of ILD and for the optimization of the indications of HRCT in rheumatic diseases.

Background: Omega-3 is a nutritional strategie that have been used to recover muscles from exercise-induced muscle damage in a preventive perspective. Aim: To verify whether omega-3 (ω-3) supplementation after a session of resistance exercise facilitates muscle recovery in women undergoing a balanced diet. Methods: This clinical trial was registered under the number NCT02839525. Thirty healthy women (22.2 ± 3.3 years) participated in this double-blinded, placebo-controlled trial. They were randomly distributed into ω-3 ( n=15) and placebo ( n=15) groups. They ingested ω-3 fish oil (3200 mg/day) or placebo (olive oil) at the dinner after the exercise bout (10 sets of 10 unilateral eccentric contractions in a knee extension chair), as well as at lunch for the three subsequent days. In addition, both groups followed a balanced diet along the four days. Muscle soreness and maximal isometric and isokinetic voluntary contractions were assessed immediately before, and 24, 48, and 72 hours after the resistance exercise. Main findings: There was no significant group-time interaction for any outcome. Participants presented increased levels of muscle soreness and reduced muscle strength capacity along the three days after exercise. There was no difference between placebo and ω-3 groups. Conclusion: Supplementation of ω-3 fish oil for three days after resistance exercise provided no additional benefits compared to placebo supplementation on recovery of healthy young women following a balanced diet.

Background Patients receiving an implantable cardioverter defibrillator (ICD) generally adapt well to living with their device, but we know little about the prevalence of patients' body image concerns (BICs) post implant. Methods The objectives were to evaluate the psychometric properties of the ICD-BICQ, find a cut-off indicating BICs and determine the prevalence of BICs. Construct validity was determined using the Kaiser-Meyer-Olkin test, Scree-plot and Explorative Factor Analysis. Internal consistency was examined via Cronbach's alpha. Correlations to other validated questionnaires, a weighted and simple scale and a cut-off indicating BICs was evaluated. Results In total, 331 patients completed the 39-item ICD-BICQ together with: Type D Scale (DS14), Generalized Anxiety Disorder scale (GAD-7), Patient Health Questionnaire (PHQ-9), and Florida Patient Acceptance Survey (FPAS). Five patients were excluded due to reoperations, leaving 326 patients in the analyses. Results revealed a one-factor structure with 32 items and Cronbach's alpha at 0.948. A cut-off at 36 points displayed the 20% patients with the highest score of BICs. The prevalence was 29.8 % in women and 18.4 % in men. Conclusion The psychometric evaluation of the 32-item ICD-BICQ showed acceptable construct validity and internal reliability. We recommend a cut-off score at 36 points to identify patients at risk of having BICs. The prevalence of BICs indicated that both men and women are at risk of having BICs. The ICD-BICQ can be used in clinical practice to help healthcare professionals to identify patients at risk of BICs and as to evaluate BICs when implementing new operation techniques. This article is protected by copyright. All rights reserved.

Eine wichtige Entitat der Lungenkarzinome ist das kleinzellige Lungenkarzinom , das aufgrund differenter Therapien von sog. nichtkleinzelligen Karzinomen und anderen blauzelligen Tumoren unterschieden werden muss. Der Schwerpunkt der Arbeit liegt in der Darstellung der typischen histomorphologischen, immunhistochemischen und genetischen Befunde eines kleinzelligen Karzinoms sowie der relevanten Differenzialdiagnosen. Es erfolgte eine Literaturrecherche in der Datenbank PubMed sowie in der gangigen pathologischen Fachliteratur. Eine sichere Diagnosestellung dieser aggressiven Tumorentitat ist von groster Bedeutung, um schnellstmoglich eine adaquate Therapie beginnen zu konnen. Hierfur sind immunhistochemische Untersuchungen unerlasslich. Trotz maximaler Therapie zeigt sich eine eher geringe 5‑Jahres-Uberlebenswahrscheinlichkeit. Neue Immuncheckpointtherapien konnten bei einem Teil der Patienten eine hohe Wirksamkeit haben.