Showing papers by "Medical University of Graz published in 2020"
University of Washington1, National Institutes of Health2, Institute for Health Metrics and Evaluation3, Sapienza University of Rome4, Mayo Clinic5, FIU Herbert Wertheim College of Medicine6, Cincinnati Children's Hospital Medical Center7, Boston University8, Essentia Health9, University of Douala10, University of British Columbia11, Medical University of Graz12, Telethon Institute for Child Health Research13, University of Milan14, Cedars-Sinai Medical Center15, Johns Hopkins University16, University of California, San Diego17, University of Michigan18, University of Edinburgh19, University of Texas Southwestern Medical Center20, Queen Mary University of London21, University of Alabama at Birmingham22, Harvard University23, Tufts Medical Center24, All India Institute of Medical Sciences25, Northwestern University26, University of Kentucky27, Casa Sollievo della Sofferenza28, Columbia University29, Icahn School of Medicine at Mount Sinai30, University of Sydney31, University of Cape Town32, Federal University of Rio de Janeiro33, University of Ibadan34, Case Western Reserve University35, Stanford University36, Universidade Federal de Minas Gerais37, The George Institute for Global Health38, Uppsala University39, Dresden University of Technology40, King Fahd Medical City41, Tulane University42, Imperial College London43
TL;DR: CVD burden continues its decades-long rise for almost all countries outside high-income countries, and alarmingly, the age-standardized rate of CVD has begun to rise in some locations where it was previously declining in high- income countries.
3,315 citations
TL;DR: COVID-19 predominantly involves the lungs, causing DAD and leading to acute respiratory insufficiency and death may be caused by the thrombosis observed in segmental and subsegmental pulmonary arterial vessels despite the use of prophylactic anticoagulation.
Abstract: The clinicopathological basis for morbidity and mortality with SARS-CoV-2 infection is not well understood. This study reports the clinical and autopsy findings of patients who died of COVID-19.
628 citations
TL;DR: The data on a benefit for mortality and prevention of infections, at least in severely deficient individuals, appear convincing, and a worldwide public health intervention that includes vitamin D supplementation in certain risk groups, and systematic vitamin D food fortification to avoid severe vitamin D deficiency, would appear to be important.
Abstract: Vitamin D testing and the use of vitamin D supplements have increased substantially in recent years. Currently, the role of vitamin D supplementation, and the optimal vitamin D dose and status, is a subject of debate, because large interventional studies have been unable to show a clear benefit (in mostly vitamin D replete populations). This may be attributed to limitations in trial design, as most studies did not meet the basic requirements of a nutrient intervention study, including vitamin D-replete populations, too small sample sizes, and inconsistent intervention methods regarding dose and metabolites. Vitamin D deficiency (serum 25-hydroxyvitamin D [25(OH)D] 50 nmol/L or 20 ng/ml is, therefore, the primary treatment goal, although some data suggest a benefit for a higher threshold. Severe vitamin D deficiency with a 25(OH)D concentration below <30 nmol/L (or 12 ng/ml) dramatically increases the risk of excess mortality, infections, and many other diseases, and should be avoided whenever possible. The data on a benefit for mortality and prevention of infections, at least in severely deficient individuals, appear convincing. Vitamin D is clearly not a panacea, and is most likely efficient only in deficiency. Given its rare side effects and its relatively wide safety margin, it may be an important, inexpensive, and safe adjuvant therapy for many diseases, but future large and well-designed studies should evaluate this further. A worldwide public health intervention that includes vitamin D supplementation in certain risk groups, and systematic vitamin D food fortification to avoid severe vitamin D deficiency, would appear to be important. In this narrative review, the current international literature on vitamin D deficiency, its relevance, and therapeutic options is discussed.
561 citations
Katrina L. Grasby1, Neda Jahanshad2, Jodie N. Painter1, Lucía Colodro-Conde3 +356 more•Institutions (115)
TL;DR: Results support the radial unit hypothesis that different developmental mechanisms promote surface area expansion and increases in thickness and find evidence that brain structure is a key phenotype along the causal pathway that leads from genetic variation to differences in general cognitive function.
Abstract: The cerebral cortex underlies our complex cognitive capabilities, yet little is known about the specific genetic loci that influence human cortical structure. To identify genetic variants that affect cortical structure, we conducted a genome-wide association meta-analysis of brain magnetic resonance imaging data from 51,665 individuals. We analyzed the surface area and average thickness of the whole cortex and 34 regions with known functional specializations. We identified 199 significant loci and found significant enrichment for loci influencing total surface area within regulatory elements that are active during prenatal cortical development, supporting the radial unit hypothesis. Loci that affect regional surface area cluster near genes in Wnt signaling pathways, which influence progenitor expansion and areal identity. Variation in cortical structure is genetically correlated with cognitive function, Parkinson's disease, insomnia, depression, neuroticism, and attention deficit hyperactivity disorder.
436 citations
TL;DR: “So all a man could win in the conflict between plague and life was knowledge and memories”
Abstract: Min Hua Zheng 1 MD, Luigi Boni 2 MD FACS, Abe Fingerhut 1,3 MD FACS 1 Department of General Surgery, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai Minimally Invasive Surgery Center, Shanghai 200025, P. R. China 2 Department of Surgery, Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico di Milano, University of Milan, Milan, Italy 3 Surgical Research, Department of Surgery, Medical University of Graz, Austria “So all a man could win in the conflict between plague and life was knowledge and memories.” Albert Camus French writer and philosopher in “The Plague” 1947
374 citations
TL;DR: Mendelian randomisation analysis supports causal roles for several HF risk factors, and demonstrates CAD-independent effects for atrial fibrillation, body mass index, and hypertension.
Abstract: Heart failure (HF) is a leading cause of morbidity and mortality worldwide. A small proportion of HF cases are attributable to monogenic cardiomyopathies and existing genome-wide association studies (GWAS) have yielded only limited insights, leaving the observed heritability of HF largely unexplained. We report results from a GWAS meta-analysis of HF comprising 47,309 cases and 930,014 controls. Twelve independent variants at 11 genomic loci are associated with HF, all of which demonstrate one or more associations with coronary artery disease (CAD), atrial fibrillation, or reduced left ventricular function, suggesting shared genetic aetiology. Functional analysis of non-CAD-associated loci implicate genes involved in cardiac development (MYOZ1, SYNPO2L), protein homoeostasis (BAG3), and cellular senescence (CDKN1A). Mendelian randomisation analysis supports causal roles for several HF risk factors, and demonstrates CAD-independent effects for atrial fibrillation, body mass index, and hypertension. These findings extend our knowledge of the pathways underlying HF and may inform new therapeutic strategies.
326 citations
University Hospital Regensburg1, University of California, San Diego2, University of Tokyo3, University of Montpellier4, University of Southern Denmark5, Leipzig University6, University of Göttingen7, Swansea University8, Medical University of Graz9, Parker H. Petit Institute for Bioengineering & Bioscience10, University of Colorado Denver11, Cardiff University12, University of Graz13, Babraham Institute14
TL;DR: An update on both the LIPID MAPS classification system and shorthand notation of lipid structures is presented, and annotation of atoms is included for the use of stable isotope-labeled compounds in metabolic labeling experiments or as internal standards.
294 citations
TL;DR: A deep learning system able to identify the most common skin conditions may help clinicians in making more accurate diagnoses in routine clinical practice.
Abstract: Skin conditions affect 1.9 billion people. Because of a shortage of dermatologists, most cases are seen instead by general practitioners with lower diagnostic accuracy. We present a deep learning system (DLS) to provide a differential diagnosis of skin conditions using 16,114 de-identified cases (photographs and clinical data) from a teledermatology practice serving 17 sites. The DLS distinguishes between 26 common skin conditions, representing 80% of cases seen in primary care, while also providing a secondary prediction covering 419 skin conditions. On 963 validation cases, where a rotating panel of three board-certified dermatologists defined the reference standard, the DLS was non-inferior to six other dermatologists and superior to six primary care physicians (PCPs) and six nurse practitioners (NPs) (top-1 accuracy: 0.66 DLS, 0.63 dermatologists, 0.44 PCPs and 0.40 NPs). These results highlight the potential of the DLS to assist general practitioners in diagnosing skin conditions.
288 citations
TL;DR: The treatment of CAPA is complicated by drug–drug interactions associated with broad spectrum azoles, renal tropism and damage caused by SARS-CoV-2, which may challenge the use of liposomal amphotericin B, as well as the emergence of azole-resistance.
Abstract: Like severe influenza, coronavirus disease-19 (COVID-19) resulting in acute respiratory distress syndrome (ARDS) has emerged as an important disease that predisposes patients to secondary pulmonary aspergillosis, with 35 cases of COVID-19 associated pulmonary aspergillosis (CAPA) published until June 2020. The release of danger-associated molecular patterns during severe COVID-19 results in both pulmonary epithelial damage and inflammatory disease, which are predisposing risk factors for pulmonary aspergillosis. Moreover, collateral effects of host recognition pathways required for the activation of antiviral immunity may, paradoxically, contribute to a highly permissive inflammatory environment that favors fungal pathogenesis. Diagnosis of CAPA remains challenging, mainly because bronchoalveolar lavage fluid galactomannan testing and culture, which represent the most sensitive diagnostic tests for aspergillosis in the ICU, are hindered by the fact that bronchoscopies are rarely performed in COVID-19 patients due to the risk of disease transmission. Similarly, autopsies are rarely performed, which may result in an underestimation of the prevalence of CAPA. Finally, the treatment of CAPA is complicated by drug–drug interactions associated with broad spectrum azoles, renal tropism and damage caused by SARS-CoV-2, which may challenge the use of liposomal amphotericin B, as well as the emergence of azole-resistance. This clinical reality creates an urgency for new antifungal drugs currently in advanced clinical development with more promising pharmacokinetic and pharmacodynamic profiles.
274 citations
TL;DR: It is demonstrated that serum NfL levels increase in healthy aging people and predict and correlate with brain volume loss, which may be driven by subclinical comorbid pathologies.
Abstract: Neurofilament light (NfL) protein is a marker of neuro-axonal damage and can be measured not only in cerebrospinal fluid but also in serum, which allows for repeated assessments. There is still limited knowledge regarding the association of serum NfL (sNfL) with age and subclinical morphologic brain changes and their dynamics in the normal population. We measured sNfL by a single molecule array (Simoa) assay in 335 individuals participating in a population-based cohort study and after a mean follow-up time of 5.9 years (n = 103). Detailed clinical examination, cognitive testing and 3T brain MRI were performed to assess subclinical brain damage. We show that rising and more variable sNfL in individuals >60 years indicate an acceleration of neuronal injury at higher age, which may be driven by subclinical comorbid pathologies. This is supported by a close association of sNfL with brain volume changes in a cross-sectional and especially longitudinal manner. Neurofilament (NfL) levels in CSF and blood have been established as a biomarker of neuronal damage in neurodegenerative diseases, and there is an age-dependent increase in NfL levels in CSF. Here the authors demonstrate that serum NfL levels increase in healthy aging people and predict and correlate with brain volume loss.
264 citations
TL;DR: The potential role of tryptophan metabolism in the modulation of brain function by the gut microbiota, including serotonin synthesis and degradation pathways of the host, is focused on.
Goethe University Frankfurt1, University of Debrecen2, University of Bologna3, Katholieke Universiteit Leuven4, University of Padua5, University of Turin6, Autonomous University of Barcelona7, Royal Free Hospital8, Université libre de Bruxelles9, University of Alcalá10, Hospital General Universitario Gregorio Marañón11, University of Pavol Jozef Šafárik12, Ludwig Maximilian University of Munich13, Medical University of Vienna14, University of Cambridge15, Wittenberg University16, Leipzig University17, RWTH Aachen University18, Leiden University Medical Center19, Medical University of Graz20, Innsbruck Medical University21, University of Lugano22, Aarhus University Hospital23, Université Paris-Saclay24, Marmara University25, Nottingham University Hospitals NHS Trust26, University of Paris27, Ghent University Hospital28, Hannover Medical School29, University Hospital Bonn30, University of Münster31, University of Basel32, University of Birmingham33, Derriford Hospital34, University of Copenhagen35
TL;DR: Acute decompensation without ACLF is a heterogeneous condition with three different clinical courses and two major pathophysiological mechanisms: systemic inflammation and portal hypertension.
Uppsala University1, Gloucestershire Hospitals NHS Foundation Trust2, Nova Southeastern University3, University of Hamburg4, University of Amsterdam5, University of Pécs6, Catholic University of the Sacred Heart7, University of Bern8, Utrecht University9, Houston Methodist Hospital10, University of Patras11, University of Southern Denmark12, Ghent University13, Cambridge University Hospitals NHS Foundation Trust14, Asahikawa Medical University15, Medical University of Graz16, University of Adelaide17, University Health Network18, Imperial College London19, National University of Colombia20
TL;DR: Editor's Choice - European Society for Vascular Surgery (ESVS) 2020 Clinical Practice Guidelines on the Management of Acute Limb Ischaemia.
TL;DR: Recommendations for the prevention, mitigation and containment in haemodialysis centres of the emerging COVID-19 pandemic are provided to minimize the risk for other patients and personnel taking care of these patients.
Abstract: COVID-19, a disease caused by a novel coronavirus, is a major global human threat that has turned into a pandemic. This novel coronavirus has specifically high morbidity in the elderly and in comorbid populations. Uraemic patients on dialysis combine an intrinsic fragility and a very frequent burden of comorbidities with a specific setting in which many patients are repeatedly treated in the same area (haemodialysis centres). Moreover, if infected, the intensity of dialysis requiring specialized resources and staff is further complicated by requirements for isolation, control and prevention, putting healthcare systems under exceptional additional strain. Therefore, all measures to slow if not to eradicate the pandemic and to control unmanageably high incidence rates must be taken very seriously. The aim of the present review of the European Dialysis (EUDIAL) Working Group of ERA-EDTA is to provide recommendations for the prevention, mitigation and containment in haemodialysis centres of the emerging COVID-19 pandemic. The management of patients on dialysis affected by COVID-19 must be carried out according to strict protocols to minimize the risk for other patients and personnel taking care of these patients. Measures of prevention, protection, screening, isolation and distribution have been shown to be efficient in similar settings. They are essential in the management of the pandemic and should be taken in the early stages of the disease.
TL;DR: The first evidence of diffuse alveolar damage in the context of an acute respiratory distress syndrome has now been joined by the latest findings that report a more complex scenario in COVID-19, including a vascular involvement and a wide spectrum of associated pathologies.
Abstract: Since its initial recognition in December 2019, Coronavirus disease 19 (COVID-19) has quickly spread to a pandemic infectious disease. The causative agent has been recognized as a novel coronavirus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), primarily affecting the respiratory tract. To date, no vaccines are available nor any specific treatment. To limit the number of infections, strict directives have been issued by governments that have been translated into equally rigorous guidelines notably for post-mortem examinations by international and national scientific societies. The recommendations for biosafety control required during specimen collection and handling have strongly limited the practice of autopsies of the COVID-19 patients to a few adequate laboratories. A full pathological examination has always been considered an important tool to better understand the pathophysiology of diseases, especially when the knowledge of an emerging disorder is limited and the impact on the healthcare system is significant. The first evidence of diffuse alveolar damage in the context of an acute respiratory distress syndrome has now been joined by the latest findings that report a more complex scenario in COVID-19, including a vascular involvement and a wide spectrum of associated pathologies. Ancillary tools such as electron microscopy and molecular biology used on autoptic tissue samples from autopsy are also significantly contributing to confirm and/or identify new aspects useful for a deeper knowledge of the pathogenetic mechanisms. This article will review and summarize the pathological findings described in COVID-19 until now, chiefly focusing on the respiratory tract, highlighting the importance of autopsy towards a better knowledge of this disease.
University of Queensland1, Queensland Health2, University of New South Wales3, Queensland University of Technology4, French Institute of Health and Medical Research5, University of Geneva6, University of Palermo7, St George's, University of London8, University of Cambridge9, Guy's and St Thomas' NHS Foundation Trust10, University of Paris11, University of Tripoli12, Nova Southeastern University13, Medical University of Graz14, Utrecht University15, Princess Alexandra Hospital16, Ghent University17
TL;DR: Widespread shortages, frequent reuse of, and adverse effects related to PPE are reported, and urgent action by healthcare administrators, policymakers, governments and industry is warranted.
University of Washington1, University of Texas Health Science Center at Houston2, John P. Hussman Institute for Human Genomics3, Boston University4, Case Western Reserve University5, Baylor College of Medicine6, Icahn School of Medicine at Mount Sinai7, University of Pennsylvania8, Erasmus University Medical Center9, French Institute of Health and Medical Research10, Pasteur Institute11, university of lille12, Vanderbilt University Medical Center13, Washington University in St. Louis14, University of Bordeaux15, Broad Institute16, National Institutes of Health17, University of Helsinki18, University of Eastern Finland19, Harvard University20, McGill University21, University of Tampere22, Columbia University23, Indiana University24, University of Tartu25, University of Nantes26, Oulu University Hospital27, Medical University of Graz28, University of Texas at Austin29
TL;DR: The Alzheimer’s Disease Sequencing Project undertook whole exome sequencing in 5,740 late-onset Alzheimer disease cases and 5,096 cognitively normal controls primarily of European ancestry, identifying novel and predicted functional genetic variants in genes previously associated with AD.
Abstract: The Alzheimer’s Disease Sequencing Project (ADSP) undertook whole exome sequencing in 5,740 late-onset Alzheimer disease (AD) cases and 5,096 cognitively normal controls primarily of European ancestry (EA), among whom 218 cases and 177 controls were Caribbean Hispanic (CH). An age-, sex- and APOE based risk score and family history were used to select cases most likely to harbor novel AD risk variants and controls least likely to develop AD by age 85 years. We tested ~1.5 million single nucleotide variants (SNVs) and 50,000 insertion-deletion polymorphisms (indels) for association to AD, using multiple models considering individual variants as well as gene-based tests aggregating rare, predicted functional, and loss of function variants. Sixteen single variants and 19 genes that met criteria for significant or suggestive associations after multiple-testing correction were evaluated for replication in four independent samples; three with whole exome sequencing (2,778 cases, 7,262 controls) and one with genome-wide genotyping imputed to the Haplotype Reference Consortium panel (9,343 cases, 11,527 controls). The top findings in the discovery sample were also followed-up in the ADSP whole-genome sequenced family-based dataset (197 members of 42 EA families and 501 members of 157 CH families). We identified novel and predicted functional genetic variants in genes previously associated with AD. We also detected associations in three novel genes: IGHG3 (p = 9.8 × 10−7), an immunoglobulin gene whose antibodies interact with β-amyloid, a long non-coding RNA AC099552.4 (p = 1.2 × 10−7), and a zinc-finger protein ZNF655 (gene-based p = 5.0 × 10−6). The latter two suggest an important role for transcriptional regulation in AD pathogenesis.
University of Paris1, University of Barcelona2, Université Paris-Saclay3, University of Bologna4, Goethe University Frankfurt5, Katholieke Universiteit Leuven6, University of Paris-Sud7, University of Alcalá8, Université libre de Bruxelles9, University of Padua10, Autonomous University of Barcelona11, King's College London12, University of Bonn13, Ludwig Maximilian University of Munich14, University College London15, Eppendorf (Germany)16, Hospital General Universitario Gregorio Marañón17, Medical University of Graz18, Aarhus University Hospital19, Leiden University Medical Center20
TL;DR: Among patients with ACLF, the intensity of the fingerprint increased across ACLF grades, and was similar in patients with kidney failure and in those without, indicating that the fingerprint reflected not only decreased kidney excretion but also altered cell metabolism.
Manchester Academic Health Science Centre1, University of Manchester2, University Medical Center Groningen3, University of Amsterdam4, National Institutes of Health5, University of Pisa6, The George Institute for Global Health7, Imperial College London8, Medical University of Graz9, First Faculty of Medicine, Charles University in Prague10, Lund University11, University of Córdoba (Spain)12, University of Düsseldorf13
TL;DR: These sequelae implicate a high exposure to indoor allergens (house dust mites, pets, molds, etc), tobacco smoke, and other pollutants, which have an impact on respiratory health and addresses the policy adjustments and lifestyle changes required to mitigate their deleterious effects.
Abstract: Air pollution and climate change have a significant impact on human health and well-being and contribute to the onset and aggravation of allergic rhinitis and asthma among other chronic respiratory diseases. In Westernized countries, households have experienced a process of increasing insulation and individuals tend to spend most of their time indoors. These sequelae implicate a high exposure to indoor allergens (house dust mites, pets, molds, etc), tobacco smoke, and other pollutants, which have an impact on respiratory health. Outdoor air pollution derived from traffic and other human activities not only has a direct negative effect on human health but also enhances the allergenicity of some plants and contributes to global warming. Climate change modifies the availability and distribution of plant- and fungal-derived allergens and increases the frequency of extreme climate events. This review summarizes the effects of indoor air pollution, outdoor air pollution, and subsequent climate change on asthma and allergic rhinitis in children and adults and addresses the policy adjustments and lifestyle changes required to mitigate their deleterious effects.
Oslo University Hospital1, National Institutes of Health2, Durham University3, University of Pisa4, University of Florence5, University of Leeds6, University of Erlangen-Nuremberg7, Marche Polytechnic University8, Freeman Hospital9, Royal Hallamshire Hospital10, University Hospital Heidelberg11, Medical University of Graz12, Bellvitge University Hospital13, Université Paris-Saclay14, French Institute of Health and Medical Research15, University Hospital of Basel16, University of Zurich17
TL;DR: The first evidence-based consensus statements were established on guidance for the identification and medical management of systemic sclerosis-associated ILD through a robust modified Delphi process developed by a diverse panel of experts.
Abstract: Summary Background Systemic sclerosis-associated interstitial lung disease (ILD) carries a high mortality risk; expert guidance is required to aid early recognition and treatment. We aimed to develop the first expert consensus and define an algorithm for the identification and management of the condition through application of well established methods. Methods Evidence-based consensus statements for systemic sclerosis-associated ILD management were established for six domains (ie, risk factors, screening, diagnosis and severity assessment, treatment initiation and options, disease progression, and treatment escalation) using a modified Delphi process based on a systematic literature analysis. A panel of 27 Europe-based pulmonologists, rheumatologists, and internists with expertise in systemic sclerosis-associated ILD participated in three rounds of online surveys, a face-to-face discussion, and a WebEx meeting, followed by two supplemental Delphi rounds, to establish consensus and define a management algorithm. Consensus was considered achieved if at least 80% of panellists indicated agreement or disagreement. Findings Between July 1, 2018, and Aug 27, 2019, consensus agreement was reached for 52 primary statements and six supplemental statements across six domains of management, and an algorithm was defined for clinical practice use. The agreed statements most important for clinical use included: all patients with systemic sclerosis should be screened for systemic sclerosis-associated ILD using high-resolution CT; high-resolution CT is the primary tool for diagnosing ILD in systemic sclerosis; pulmonary function tests support screening and diagnosis; systemic sclerosis-associated ILD severity should be measured with more than one indicator; it is appropriate to treat all severe cases; no pharmacological treatment is an option for some patients; follow-up assessments enable identification of disease progression; progression pace, alongside disease severity, drives decisions to escalate treatment. Interpretation Through a robust modified Delphi process developed by a diverse panel of experts, the first evidence-based consensus statements were established on guidance for the identification and medical management of systemic sclerosis-associated ILD. Funding An unrestricted grant from Boehringer Ingelheim International.
TL;DR: Both sources and consequences of mitochondrial ROS during IR and in the chronic setting following MI are discussed, thereby emphasizing the potential therapeutic value of attenuating mitochondrial ROS to improve outcome and prognosis for patients suffering MI.
TL;DR: The COVID-19 pandemic presents important lessons to strengthen health systems through better connection between public health, primary care, and secondary care to cope better with future waves of this and other pandemics.
Abstract: The COVID-19 pandemic has modified organisation and processes of primary care. In this paper, we aim to summarise experiences of international primary care systems. We explored personal accounts and findings in reporting on the early experiences from primary care during the pandemic, through the online Global Forum on Universal Health Coverage and Primary Health Care. During the early stage of the pandemic, primary care continued as the first point of contact to the health system but was poorly informed by policy makers on how to fulfil its role and ill equipped to provide care while protecting staff and patients against further spread of the infection. In many countries, the creativity and initiatives of local health professionals led to the introduction or extension of the use of telephone, e-mail and virtual consulting, and introduced triaging to separate 'suspected' COVID-19 from non-COVID-19 care. There were substantial concerns of collateral damage to the health of the population due to abandoned or postponed routine care. The pandemic presents important lessons to strengthen health systems through better connection between public health, primary care, and secondary care to cope better with future waves of this and other pandemics.
TL;DR: Despite the marked immune dysregulation in COVID-19, no prominent defects have been reported in immune cells that are critically required for immunity to Candida, which suggests that relevant clinical factors, including prolonged ICU stays, central venous catheters, and broad-spectrum antibiotic use, may be key factors causing COVIDs patients to develop IYIs.
Abstract: The recent global pandemic of COVID-19 has predisposed a relatively high number of patients to acute respiratory distress syndrome (ARDS), which carries a risk of developing super-infections. Candida species are major constituents of the human mycobiome and the main cause of invasive fungal infections, with a high mortality rate. Invasive yeast infections (IYIs) are increasingly recognized as s complication of severe COVID-19. Despite the marked immune dysregulation in COVID-19, no prominent defects have been reported in immune cells that are critically required for immunity to Candida. This suggests that relevant clinical factors, including prolonged ICU stays, central venous catheters, and broad-spectrum antibiotic use, may be key factors causing COVID-19 patients to develop IYIs. Although data on the comparative performance of diagnostic tools are often lacking in COVID-19 patients, a combination of serological and molecular techniques may present a promising option for the identification of IYIs. Clinical awareness and screening are needed, as IYIs are difficult to diagnose, particularly in the setting of severe COVID-19. Echinocandins and azoles are the primary antifungal used to treat IYIs, yet the therapeutic failures exerted by multidrug-resistant Candida spp. such as C. auris and C. glabrata call for the development of new antifungal drugs with novel mechanisms of action.
Saarland University1, Rush University Medical Center2, RWTH Aachen University3, Erasmus University Rotterdam4, Leipzig University5, Medical University of Graz6, University of Zurich7, Heidelberg University8, Synlab Group9, Maastricht University10, ETH Zurich11, University of Bonn12, University of Massachusetts Medical School13
TL;DR: It is demonstrated that ApoC3 activates the NLRP3 inflammasome via a non-canonical pathway contributing to inflammation and development of atherosclerosis.
Abstract: NLRP3-inflammasome-driven inflammation is involved in the pathogenesis of a variety of diseases. Identification of endogenous inflammasome activators is essential for the development of new anti-inflammatory treatment strategies. Here, we identified that apolipoprotein C3 (ApoC3) activates the NLRP3 inflammasome in human monocytes by inducing an alternative NLRP3 inflammasome via caspase-8 and dimerization of Toll-like receptors 2 and 4. Alternative inflammasome activation in human monocytes is mediated by the Toll-like receptor adapter protein SCIMP. This triggers Lyn/Syk-dependent calcium entry and the production of reactive oxygen species, leading to activation of caspase-8. In humanized mouse models, ApoC3 activated human monocytes in vivo to impede endothelial regeneration and promote kidney injury in an NLRP3- and caspase-8-dependent manner. These data provide new insights into the regulation of the NLRP3 inflammasome and the pathophysiological role of triglyceride-rich lipoproteins containing ApoC3. Targeting ApoC3 might prevent organ damage and provide an anti-inflammatory treatment for vascular and kidney diseases.
TL;DR: During the current COVID-19 crisis, it appeared that telemedicine can be considered as an electronic personal protective equipment by reducing the number of physical contacts and risk contamination.
Abstract: With the COVID-19 crisis, recommendations for personal protective equipment (PPE) are necessary for protection in orthopaedics and traumatology. The primary purpose of this study is to review and present current evidence and recommendations for personal protective equipment and safety recommendations for orthopaedic surgeons and trauma surgeons. A systematic review of the available literature was performed using the keyword terms “COVID-19”, “Coronavirus”, “surgeon”, “health-care workers”, “protection”, “masks”, “gloves”, “gowns”, “helmets”, and “aerosol” in several combinations. The following databases were assessed: Pubmed, Cochrane Reviews, Google Scholar. Due to the paucity of available data, it was decided to present it in a narrative manner. In addition, participating doctors were asked to provide their guidelines for PPE in their countries (Austria, Luxembourg, Switzerland, Germany, UK) for consideration in the presented practice recommendations. World Health Organization guidance for respiratory aerosol-generating procedures (AGPs) such as intubation in a COVID19 environment was clear and included the use of an FFP3 (filtering face piece level 3) mask and face protection. However, the recommendation for surgical AGPs, such as the use of high-speed power tools in the operating theatre, was not clear until the UK Public Health England (PHE) guidance of 27 March 2020. This guidance included FFP3 masks and face protection, which UK surgeons quickly adopted. The recommended PPE for orthopaedic surgeons, working in a COVID19 environment, should consist of level 4 surgical gowns, face shields or goggles, double gloves, FFP2-3 or N95-99 respirator masks. An alternative to the mask, face shield and goggles is a powered air-purifying respirator, particularly if the surgeons fail the mask fit test or are required to undertake a long procedure. However, there is a high cost and limited availabilty of these devices at present. Currently available surgical helmets and toga systems may not be the solution due to a permeable top for air intake. During the current COVID-19 crisis, it appeared that telemedicine can be considered as an electronic personal protective equipment by reducing the number of physical contacts and risk contamination. Orthopaedic and trauma surgery using power tools, pulsatile lavage and electrocautery are surgical aerosol-generating procedures and all body fluids contain virus particles. Raising awareness of these issues will help avoid occupational transmission of COVID-19 to the surgical team by aerosolization of blood or other body fluids and hence adequate PPE should be available and used during orthopaedic surgery. In addition, efforts have to be made to improve the current evidence in this regard. IV.
TL;DR: This review article provides an overview of the crucial steps in MS-based lipidomics workflows, including sample preparation, either liquid–liquid or solid-phase extraction, derivatization, chromatography, ion-mobility spectrometry, MS, and data processing by various software packages.
Abstract: Lipids are amongst the most important organic compounds in living organisms, where they serve as building blocks for cellular membranes as well as energy storage and signaling molecules. Lipidomics is the science of the large-scale determination of individual lipid species, and the underlying analytical technology that is used to identify and quantify the lipidome is generally mass spectrometry (MS). This review article provides an overview of the crucial steps in MS-based lipidomics workflows, including sample preparation, either liquid–liquid or solid-phase extraction, derivatization, chromatography, ion-mobility spectrometry, MS, and data processing by various software packages. The associated concepts are discussed from a technical perspective as well as in terms of their application. Furthermore, this article sheds light on recent advances in the technology used in this field and its current limitations. Particular emphasis is placed on data quality assurance and adequate data reporting; some of the most common pitfalls in lipidomics are discussed, along with how to circumvent them.
Ido Didi Fabian1, Ido Didi Fabian2, Elhassan Abdallah3, Shehu U. Abdullahi4 +473 more•Institutions (155)
TL;DR: This cross-sectional analysis reports the retinoblastoma stage at diagnosis across the world during a single year, investigates associations between clinical variables and national income level, and investigates risk factors for advanced disease at diagnosis.
Abstract: Importance: Early diagnosis of retinoblastoma, the most common intraocular cancer, can save both a child's life and vision. However, anecdotal evidence suggests that many children across the world are diagnosed late. To our knowledge, the clinical presentation of retinoblastoma has never been assessed on a global scale. Objectives: To report the retinoblastoma stage at diagnosis in patients across the world during a single year, to investigate associations between clinical variables and national income level, and to investigate risk factors for advanced disease at diagnosis. Design, Setting, and Participants: A total of 278 retinoblastoma treatment centers were recruited from June 2017 through December 2018 to participate in a cross-sectional analysis of treatment-naive patients with retinoblastoma who were diagnosed in 2017. Main Outcomes and Measures: Age at presentation, proportion of familial history of retinoblastoma, and tumor stage and metastasis. Results: The cohort included 4351 new patients from 153 countries; the median age at diagnosis was 30.5 (interquartile range, 18.3-45.9) months, and 1976 patients (45.4%) were female. Most patients (n = 3685 [84.7%]) were from low- and middle-income countries (LMICs). Globally, the most common indication for referral was leukocoria (n = 2638 [62.8%]), followed by strabismus (n = 429 [10.2%]) and proptosis (n = 309 [7.4%]). Patients from high-income countries (HICs) were diagnosed at a median age of 14.1 months, with 656 of 666 (98.5%) patients having intraocular retinoblastoma and 2 (0.3%) having metastasis. Patients from low-income countries were diagnosed at a median age of 30.5 months, with 256 of 521 (49.1%) having extraocular retinoblastoma and 94 of 498 (18.9%) having metastasis. Lower national income level was associated with older presentation age, higher proportion of locally advanced disease and distant metastasis, and smaller proportion of familial history of retinoblastoma. Advanced disease at diagnosis was more common in LMICs even after adjusting for age (odds ratio for low-income countries vs upper-middle-income countries and HICs, 17.92 [95% CI, 12.94-24.80], and for lower-middle-income countries vs upper-middle-income countries and HICs, 5.74 [95% CI, 4.30-7.68]). Conclusions and Relevance: This study is estimated to have included more than half of all new retinoblastoma cases worldwide in 2017. Children from LMICs, where the main global retinoblastoma burden lies, presented at an older age with more advanced disease and demonstrated a smaller proportion of familial history of retinoblastoma, likely because many do not reach a childbearing age. Given that retinoblastoma is curable, these data are concerning and mandate intervention at national and international levels. Further studies are needed to investigate factors, other than age at presentation, that may be associated with advanced disease in LMICs.
Hospital Sant Joan de Déu Barcelona1, Swiss Institute of Allergy and Asthma Research2, University of Southampton3, St Mary's Hospital4, University Hospital Southampton NHS Foundation Trust5, Medical University of Graz6, CEU San Pablo University7, Carlos III Health Institute8, Istanbul Medeniyet University9, I.M. Sechenov First Moscow State Medical University10, University of Pisa11, Charité12, National Institutes of Health13, Odense University Hospital14, Istanbul University15, University of Padua16, University of Messina17, University of Marburg18, Imperial College London19
TL;DR: This user's guide reviews current knowledge and aims to provide clinical guidance to healthcare professionals taking care of children undergoing allergen immunotherapy to improve the patient's adherence to the treatment.
Abstract: Allergen immunotherapy is a cornerstone in the treatment of allergic children. The clinical efficiency relies on a well-defined immunologic mechanism promoting regulatory T cells and downplaying the immune response induced by allergens. Clinical indications have been well documented for respiratory allergy in the presence of rhinitis and/or allergic asthma, to pollens and dust mites. Patients who have had an anaphylactic reaction to hymenoptera venom are also good candidates for allergen immunotherapy. Administration of allergen is currently mostly either by subcutaneous injections or by sublingual administration. Both methods have been extensively studied and have pros and cons. Specifically in children, the choice of the method of administration according to the patient's profile is important. Although allergen immunotherapy is widely used, there is a need for improvement. More particularly, biomarkers for prediction of the success of the treatments are needed. The strength and efficiency of the immune response may also be boosted by the use of better adjuvants. Finally, novel formulations might be more efficient and might improve the patient's adherence to the treatment. This user's guide reviews current knowledge and aims to provide clinical guidance to healthcare professionals taking care of children undergoing allergen immunotherapy.
University of Navarra1, Charles University in Prague2, University of Debrecen3, University of Liège4, National and Kapodistrian University of Athens5, Alexandra Hospital6, Jagiellonian University7, Instituto Português de Oncologia Francisco Gentil8, University Hospitals of Leicester NHS Trust9, Medical University of Graz10, Curie Institute11, Bellvitge University Hospital12
TL;DR: In this study, avoiding the uterine manipulator and using maneuvers to avoid tumor spread at the time of colpotomy in minimally invasive surgery was associated with similar outcomes to open surgery.
Abstract: Background Minimally invasive surgery in cervical cancer has demonstrated in recent publications worse outcomes than open surgery. The primary objective of the SUCCOR study, a European, multicenter, retrospective, observational cohort study was to evaluate disease-free survival in patients with stage IB1 (FIGO 2009) cervical cancer undergoing open vs minimally invasive radical hysterectomy. As a secondary objective, we aimed to investigate the association between protective surgical maneuvers and the risk of relapse. Methods We obtained data from 1272 patients that underwent a radical hysterectomy by open or minimally invasive surgery for stage IB1 cervical cancer (FIGO 2009) from January 2013 to December 2014. After applying all the inclusion-exclusion criteria, we used an inverse probability weighting to construct a weighted cohort of 693 patients to compare outcomes (minimally invasive surgery vs open). The first endpoint compared disease-free survival at 4.5 years in both groups. Secondary endpoints compared overall survival among groups and the impact of the use of a uterine manipulator and protective closure of the colpotomy over the tumor in the minimally invasive surgery group. Results Mean age was 48.3 years (range; 23–83) while the mean BMI was 25.7 kg/m2 (range; 15–49). The risk of recurrence for patients who underwent minimally invasive surgery was twice as high as that in the open surgery group (HR, 2.07; 95% CI, 1.35 to 3.15; P=0.001). Similarly, the risk of death was 2.42-times higher than in the open surgery group (HR, 2.45; 95% CI, 1.30 to 4.60, P=0.005). Patients that underwent minimally invasive surgery using a uterine manipulator had a 2.76-times higher hazard of relapse (HR, 2.76; 95% CI, 1.75 to 4.33; P Conclusions Minimally invasive surgery in cervical cancer increased the risk of relapse and death compared with open surgery. In this study, avoiding the uterine manipulator and using maneuvers to avoid tumor spread at the time of colpotomy in minimally invasive surgery was associated with similar outcomes to open surgery. Further prospective studies are warranted.
TL;DR: Nemolizumab resulted in a greater reduction in pruritus and severity of skin lesions than placebo in patients with prurigo nodularis but was associated with adverse events.
Abstract: Background Prurigo nodularis is a chronic pruritic skin disease with multiple nodular skin lesions. Nemolizumab is a monoclonal antibody targeting the interleukin-31 receptor, which is inv...