Landspítali University Hospital Research Archive
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Docosahexaenoic Acid Modulates NK Cell Effects on Neutrophils and Their Crosstalk.
Get PDFTo access publisher's full text version of this article, please click on the hyperlink in Additional Links field or click on the hyperlink at the top of the page marked DownloadNatural killer (NK) cells and neutrophils engage in crosstalk that is important in inflammation and likely also for resolution of inflammation. NK cells activate neutrophils and induce their infiltration to the inflamed sites but may also influence their apoptosis and their subsequent efferocytosis by macrophages. Several studies indicate that docosahexaenoic acid (DHA) can inhibit NK cell cytotoxicity but the effects of DHA on the ability of NK cells to engage in crosstalk with neutrophils and affect their functions have not been described. This study explored the kinetics of the effects of NK cells and NK cells pre-treated with DHA on neutrophil surface molecule expression and apoptosis, as well as the ability of NK cells to affect other neutrophil functions. In addition, the study explored the effects of neutrophils on NK cell phenotype and function. Primary NK cells were pre-incubated with or without DHA, then stimulated and co-cultured with freshly isolated neutrophils. When co-cultured with NK cells, neutrophils had higher expression levels of CD11b and CD47; secreted more IL-8, IL-1ra, and CXCL10; had increased phagocytic ability; and their apoptosis was increased early after initiation of the co-culture while dampened at a later time-point. Pre-incubation of NK cells with DHA attenuated NK cell-induced upregulation of CD11b and CD47 on neutrophils, had minor effects on NK cell induction of cytokine/chemokine secretion or their phagocytic ability. Neutrophils also affected the function of NK cells, lowering the frequency of NKp46+ and CXCR3+ NK cells and increasing the concentrations of IFN-γ, TNF-α, and GM-CSF in the co-cultures. Pre-incubation of NK cells with DHA further decreased the frequency of NKp46+ NK cells in the co-culture with neutrophils and decreased the concentrations of IFN-γ, CCL3 and GM-CSF. These findings indicate that NK cells have mostly pro-inflammatory effects on neutrophils and that DHA can attenuate some of these pro-inflammatory effects. Neutrophils had both anti- and pro-inflammatory effects on NK cells. When NK cells had been pre-treated with DHA, the anti-inflammatory effects were increased and some of the pro-inflammatory effects attenuated. Overall, the results suggest that DHA may lead to a more anti-inflammatory microenvironment for NK cell and neutrophil crosstalk.Icelandic Research Fund
University of Iceland Research Fund
Landspitali University Hospital Research Fund
Memorial Fund of Helga Jonsdottir and Sigurlidi Kristjansso
The reliability of a deep learning model in clinical out-of-distribution MRI data: A multicohort study.
No full textTo access publisher's full text version of this article, please click on the hyperlink in Additional Links field or click on the hyperlink at the top of the page marked DownloadDeep learning (DL) methods have in recent years yielded impressive results in medical imaging, with the potential to function as clinical aid to radiologists. However, DL models in medical imaging are often trained on public research cohorts with images acquired with a single scanner or with strict protocol harmonization, which is not representative of a clinical setting. The aim of this study was to investigate how well a DL model performs in unseen clinical datasets-collected with different scanners, protocols and disease populations-and whether more heterogeneous training data improves generalization. In total, 3117 MRI scans of brains from multiple dementia research cohorts and memory clinics, that had been visually rated by a neuroradiologist according to Scheltens' scale of medial temporal atrophy (MTA), were included in this study. By training multiple versions of a convolutional neural network on different subsets of this data to predict MTA ratings, we assessed the impact of including images from a wider distribution during training had on performance in external memory clinic data. Our results showed that our model generalized well to datasets acquired with similar protocols as the training data, but substantially worse in clinical cohorts with visibly different tissue contrasts in the images. This implies that future DL studies investigating performance in out-of-distribution (OOD) MRI data need to assess multiple external cohorts for reliable results. Further, by including data from a wider range of scanners and protocols the performance improved in OOD data, which suggests that more heterogeneous training data makes the model generalize better. To conclude, this is the most comprehensive study to date investigating the domain shift in deep learning on MRI data, and we advocate rigorous evaluation of DL models on clinical data prior to being certified for deployment.
Keywords: Clinical application; Deep learning; Domain shift; Neuroimaging.Swedish Foundation for Strategic Research
Swedish Research Council
Strategic Research Programme in Neuroscience at Karolinska Institutet (StratNeuro)
Swedish Brain Power
Swedish Research Council
Stockholm County Council
Karolinska Institutet
Hjarnfonden
DOD ADNI (Department of Defense)
W81XWH-12-2-0012
United States Department of Health & Human Services
National Institutes of Health (NIH) - USA
NIH National Institute on Aging (NIA)
United States Department of Health & Human Services
National Institutes of Health (NIH) - USA
NIH National Institute of Biomedical Imaging & Bioengineering (NIBIB)
AbbVie
Alzheimer's Association
Alzheimer's Drug Discovery Foundation
Araclon Biotech
BioClinica, Inc.
Biogen
Bristol-Myers Squibb
CereSpir, Inc.
Cogstate
Eisai Co Ltd
Elan Pharmaceuticals, Inc.
Eli Lilly
EuroImmun
Hoffmann-La Roche
Roche Holding
Genentech
Fujirebio
GE Healthcare
Janssen Alzheimer Immunotherapy Research & Development, LLC.
Johnson & Johnson USA
Lumosity
Lundbeck Corporation
Merck & Company
Meso Scale Diagnostics, LLC.
NeuroRx Research
Neurotrack Technologies
Novartis
Pfizer
Piramal Imaging
Servier
Takeda Pharmaceutical Company Ltd
Transition Therapeutics
Canadian Institutes of Health Research (CIHR)
Centrum for innovativ medicin (CIMED)
Alzheimerfonden
Ake Wiberg Foundation
Birgitta och Sten Westerberg
United States Department of Health & Human Services
National Institutes of Health (NIH) - USA
NIH National Institute of Neurological Disorders & Stroke (NINDS
Predictors of Food Sensitization in Children and Adults Across Europe.
Get PDFTo access publisher's full text version of this article, please click on the hyperlink in Additional Links field or click on the hyperlink at the top of the page marked DownloadBackground: The geographical variation and temporal increase in the prevalence of food sensitization (FS) suggest environmental influences.
Objective: To investigate how environment, infant diet, and demographic characteristics, are associated with FS in children and adults, focusing on early-life exposures.
Methods: Data on childhood and adult environmental exposures (including, among others, sibship size, day care, pets, farm environment, and smoking), infant diet (including breast-feeding and timing of introduction to infant formula and solids), and demographic characteristics were collected from 2196 school-age children and 2185 adults completing an extensive questionnaire and blood sampling in the cross-sectional pan-European EuroPrevall project. Multivariable logistic regression was applied to determine associations between the predictor variables and sensitization to foods commonly implicated in food allergy (specific IgE ≥0.35 kUA/L). Secondary outcomes were inhalant sensitization and primary (non-cross-reactive) FS.
Results: Dog ownership in early childhood was inversely associated with childhood FS (odds ratio, 0.65; 95% CI, 0.48-0.90), as was higher gestational age at delivery (odds ratio, 0.93 [95% CI, 0.87-0.99] per week increase in age). Lower age and male sex were associated with a higher prevalence of adult FS (odds ratio, 0.97 [95% CI, 0.96-0.98] per year increase in age, and 1.39 [95% CI, 1.12-1.71] for male sex). No statistically significant associations were found between other evaluated environmental determinants and childhood or adult FS, nor between infant diet and childhood FS, although early introduction of solids did show a trend toward prevention of FS.
Conclusions: Dog ownership seems to protect against childhood FS, but independent effects of other currently conceived environmental and infant dietary determinants on FS in childhood or adulthood could not be confirmed.
Keywords: Dog; Early-life exposures; Environment; Europe; Food allergy; Food sensitization; Infant diet; Inhalant sensitization; Predictors; Risk factors.European Union through EuroPreval
TFOS European Ambassador meeting: Unmet needs and future scientific and clinical solutions for ocular surface diseases.
No full textTo access publisher's full text version of this article click on the hyperlink belowThe mission of the Tear Film & Ocular Surface Society (TFOS) is to advance the research, literacy, and educational aspects of the scientific field of the tear film and ocular surface. Fundamental to fulfilling this mission is the TFOS Global Ambassador program. TFOS Ambassadors are dynamic and proactive experts, who help promote TFOS initiatives, such as presenting the conclusions and recommendations of the recent TFOS DEWS II™, throughout the world. They also identify unmet needs, and propose future clinical and scientific solutions, for management of ocular surface diseases in their countries. This meeting report addresses such needs and solutions for 25 European countries, as detailed in the TFOS European Ambassador meeting in Rome, Italy, in September 2019
Immediate and long-term need for permanent cardiac pacing following aortic valve replacement.
No full textTo access publisher's full text version of this article click on the hyperlink belowIntroduction: Atrioventricular (AV) node conduction disturbances are common following surgical aortic valve replacement (SAVR), and in some cases the patient needs a permanent pacemaker (PPM) implantation before discharge from hospital. Little is known about the long-term need for PPM and the PPM dependency of these individuals. We determined the incidence of PPM implantation before and after discharge in SAVR patients. Methods: We studied 557 consecutive patients who underwent SAVR for aortic stenosis in Iceland between 2002 and 2016. Timing and indication for PPM were registered, with a new concept, ventricular pacing proportion (VPP), defined as ventricular pacing ≥90% of the time, being used to approximate pacemaker dependency. The median follow-up time was 73 months. We plotted the cumulative incidence of pacemaker implantation, treating death as a competing risk. Results: Of the 557 patients, 22 (3.9%) received PPM in the first 30 days after surgery, most commonly for complete AV block (n = 14) or symptomatic bradycardia (n = 8); Thirty-eight other patients (6.8%) had a PPM implanted >30 days postoperatively, at a median of 43 months after surgery (range 0‒181), most often for AV block (n = 13) or sick-sinus syndrome (n = 10). The cumulative incidence of PPM implantation at 1, 5, and 10 years postoperatively was 5.0%, 9.2%, and 12.3%, respectively. During follow-up, 45.0% of the 60 patients had VPP ≥90%. Conclusion: The cumulative incidence of permanent pacemaker implantation following SAVR was about 12% at 10 years, with every other patient having VPP ≥90% during follow-up. This suggests that AV node conduction disturbances extend significantly beyond the perioperative period.Landspitali University Research Fund
University of Iceland Research Fun
Lipoprotein(a) Concentration and Risks of Cardiovascular Disease and Diabetes.
No full textTo access publisher's full text version of this article click on the hyperlink belowBackground: Lipoprotein(a) [Lp(a)] is a causal risk factor for cardiovascular diseases that has no established therapy. The attribute of Lp(a) that affects cardiovascular risk is not established. Low levels of Lp(a) have been associated with type 2 diabetes (T2D).
Objectives: This study investigated whether cardiovascular risk is conferred by Lp(a) molar concentration or apolipoprotein(a) [apo(a)] size, and whether the relationship between Lp(a) and T2D risk is causal.
Methods: This was a case-control study of 143,087 Icelanders with genetic information, including 17,715 with coronary artery disease (CAD) and 8,734 with T2D. This study used measured and genetically imputed Lp(a) molar concentration, kringle IV type 2 (KIV-2) repeats (which determine apo(a) size), and a splice variant in LPA associated with small apo(a) but low Lp(a) molar concentration to disentangle the relationship between Lp(a) and cardiovascular risk. Loss-of-function homozygotes and other subjects genetically predicted to have low Lp(a) levels were evaluated to assess the relationship between Lp(a) and T2D.
Results: Lp(a) molar concentration was associated dose-dependently with CAD risk, peripheral artery disease, aortic valve stenosis, heart failure, and lifespan. Lp(a) molar concentration fully explained the Lp(a) association with CAD, and there was no residual association with apo(a) size. Homozygous carriers of loss-of-function mutations had little or no Lp(a) and increased the risk of T2D.
Conclusions: Molar concentration is the attribute of Lp(a) that affects risk of cardiovascular diseases. Low Lp(a) concentration (bottom 10%) increases T2D risk. Pharmacologic reduction of Lp(a) concentration in the 20% of individuals with the greatest concentration down to the population median is predicted to decrease CAD risk without increasing T2D risk.
Keywords: Lp(a); Mendelian randomization; coronary artery disease; genetics; type 2 diabetes
Genome-wide meta-analysis identifies eight new susceptibility loci for cutaneous squamous cell carcinoma.
Get PDFTo access publisher's full text version of this article, please click on the hyperlink in Additional Links field or click on the hyperlink at the top of the page marked DownloadCutaneous squamous cell carcinoma (SCC) is one of the most common cancers in the United States. Previous genome-wide association studies (GWAS) have identified 14 single nucleotide polymorphisms (SNPs) associated with cutaneous SCC. Here, we report the largest cutaneous SCC meta-analysis to date, representing six international cohorts and totaling 19,149 SCC cases and 680,049 controls. We discover eight novel loci associated with SCC, confirm all previously associated loci, and perform fine mapping of causal variants. The novel SNPs occur within skin-specific regulatory elements and implicate loci involved in cancer development, immune regulation, and keratinocyte differentiation in SCC susceptibility.United States Department of Health & Human Services
National Institutes of Health (NIH) - USA
NIH National Human Genome Research Institute (NHGRI)
United States Department of Health & Human Services
National Institutes of Health (NIH) - USA
Walther Cancer Foundation
Damon Runyon Cancer Research Foundation
Erasmus Medical Center and Erasmus University Rotterdam
Netherlands Organization for Health Research and Development
Research Institute for Diseases in the Elderly (RIDE)
Ministry of Education, Culture, Sports, Science and Technology, Japan (MEXT)
Ministry for Health, Welfare and Sports
European Commission Joint Research Centre
Municipality of Rotterda
Ashwagandha-induced liver injury: A case series from Iceland and the US Drug-Induced Liver Injury Network.
No full textTo access publisher's full text version of this article click on the hyperlink belowBackground & aims: Ashwagandha (Withania somnifera) is widely used in Indian Ayurvedic medicine. Several dietary supplements containing ashwagandha are marketed in the US and Europe, but only one case of drug-induced liver injury (DILI) due to ashwagandha has been published. The aim of this case series was to describe the clinical phenotype of suspected ashwagandha-induced liver injury.
Methods: Five cases of liver injury attributed to ashwagandha-containing supplements were identified; three were collected in Iceland during 2017-2018 and two from the Drug-Induced Liver Injury Network (DILIN) in 2016. Other causes for liver injury were excluded. Causality was assessed using the DILIN structured expert opinion causality approach.
Results: Among the five patients, three were males; mean age was 43 years (range 21-62). All patients developed jaundice and symptoms such as nausea, lethargy, pruritus and abdominal discomfort after a latency of 2-12 weeks. Liver injury was cholestatic or mixed (R ratios 1.4-3.3). Pruritus and hyperbilirubinaemia were prolonged (5-20 weeks). No patient developed hepatic failure. Liver tests normalized within 1-5 months in four patients. One patient was lost to follow-up. One biopsy was performed, showing acute cholestatic hepatitis. Chemical analysis confirmed ashwagandha in available supplements; no other toxic compounds were identified. No patient was taking potentially hepatotoxic prescription medications, although four were consuming additional supplements, and in one case, rhodiola was a possible causative agent along with ashwagandha.
Conclusions: These cases illustrate the hepatotoxic potential of ashwagandha. Liver injury is typically cholestatic or mixed with severe jaundice and pruritus, but self-limited with liver tests normalizing in 1-5 months.United States Department of Health & Human Services
National Institutes of Health (NIH) - USA
NIH National Institute of Diabetes & Digestive & Kidney Diseases (NIDDK)
Intramural Division of the National Cancer Institute (NCI), NI
Swift Spontaneous Regression of a Pediatric Traumatic Acute Subdural Hematoma.
Get PDFTo access publisher's full text version of this article, please click on the hyperlink in Additional Links field or click on the hyperlink at the top of the page marked DownloadWe report the case of a 4-year-old girl with acute subdural hematoma who presented to the emergency department after an unwitnessed fall of the balcony. The hematoma was hyperdense along the left convexity of 9 mm thickness with a consequent mass effect with obliteration of the adjacent sulci, left lateral ventricle compression and a midline shift of 7 mm. During her stay in the emergency department while waiting for transfer to the children intensive care unit elsewhere she slightly deteriorated neurologically. Repeat CT scan of the brain 4 h after initial presentation remarkably showed that the subdural hematoma had now largely disappeared, with a decrease in volume and density. Consequently, the mass effect diminished with a near normalization of the midline shift
Surgical nurses’ self-assessment of competence: a descriptive cross-sectional study
No full textTo access publisher's full text version of this article, please click on the hyperlink in Additional Links field or click on the hyperlink at the top of the page marked DownloadTilgangur. heilbrigðisstarfsmenn, sem búa yfir tilskilinni hæfni, eru
ein af undirstöðum farsællar starfsemi háskólasjúkrahúss enda tengist hæfni öryggi og afdrifum sjúklinga. Markmið rannsóknarinnar
var að kanna hvernig hjúkrunarfræðingar á skurðlækningasviði
Landspítala meta hæfni sína.
Aðferð. rannsóknin er þversniðsrannsókn og gögnum var safnað
árið 2016 með spurningalista. hjúkrunarfræðingar á sviðinu voru
beðnir að meta hæfni sína með nurse Competence Scale (nCS) sem
inniheldur 73 atriði og skiptist í 7 hæfniþætti (umönnun, kennsluog leiðbeinendahlutverk, greiningarhlutverk, stjórnun á aðstæðum,
hjúkrunaríhlutanir, trygging gæða og starfshlutverk). Spurt var um
hæfni á kvarðanum 0 (mjög lítil hæfni) til 10 (mjög mikil hæfni) fyrir
hvert atriði og hversu oft það væri framkvæmt (1=mjög sjaldan, 2=
öðru hverju, 3=mjög oft, 0=á ekki við). gögn voru greind með
lýsandi tölfræði og ályktunartölfræði.
Niðurstöður. Þátttakendur (n=66) mátu hæfni sína að meðaltali 7,2
(sf 1,1), mesta í umönnunarhlutverki en minnsta í að tryggja gæði.
hjúkrunarfræðingar með framhaldsnám/viðbótarmenntun mátu
heildarhæfni sína marktækt meiri en aðrir í umönnunarhlutverki,
starfshlutverki, kennslu- og leiðbeinendahlutverki og við hjúkrunaríhlutanir. Starfsaldur við hjúkrun hafði ekki áhrif á heildarhæfni en
aðhvarfsgreining sýndi að starfsaldur á deild og viðbótarnám skýrðu
14% af breytileika í hæfni.Í 22 atriðum af 73 mat yfir helmingur hjúkrunarfræðinga hæfni sína undir miðgildi allra þátttakenda og fólu þau
atriði í sér meðal annars fræðslu til skjólstæðinga og samstarfsfólks,
nýtingu hjúkrunarrannsókna og virka þátttöku í þróun hjúkrunar.
Ályktanir. niðurstöður rannsóknarinnar benda til þess að framhaldsnám/viðbótarnám ásamt starfsaldri á deild hafi áhrif á hæfni
hjúkrunarfræðinga á skurðlækningasviði. Mikilvægt er að hjúkrunarfræðingum sé gert klei að mennta sig frekar. auka þarf framboð á sérhæfðri þjálfun og fræðslu þar sem niðurstöður varðandi
starfsaldur benda til að sérhæfing í hjúkrun hafi aukist. kanna þarf
betur hvort hjúkrunarfræðingarfá nægilega krefandi tækifæri í starfi
og hvort stofnunin nýtir starfskrafta hjúkrunarfræðinga með viðbótarmenntun eins og best verður á kosið.Aim. healthcare professionals who have required competencies
are one of the pillars of successful operations of a university hospital, as competence relates to patient safety and outcome. e aim
of the study was to explore how nurses in Surgical Services at
Landspítali university hospital assess their competence.
Method. is was a cross-sectional study and data were gathered
in 2016 using a questionnaire. nurses were asked to self-assess
their competence using the nurse Competence Scale (nCS) which
comprises 73 items in seven categories (helping role, teaching/
coaching role, diagnostic functions, managing situations, therapeutic interventions, ensuring quality and work role). Participants
assessed their competence for each item on a scale of 0 (very low
competence) to 10 (very high competence), and frequency of use
(1= very rare, 2= occasional, 3= very frequent, 0= not applicable).
e data were analysed using descriptive statistics and inferential
statistics.
Results. e participants (n= 66) assessed their total competence
on average at 7.2 (SD 1.1), highest for the helping role, and lowest
for ensuring quality. Self-assessed competence was significantly
higher for nurses with postgraduate qualifications than for those
without such qualifications, in helping role, work role, teaching/
coaching role and therapeutic interventions. no difference was observed in self-assessed competence relating to experience in nursing, but regression analysis revealed that 14% of the variation was
attributable to years of experience in a unit and postgraduate qualifications. in 22 items out of 73, ≥ 50% of nurses assessed their
competence below the median value of all participants. ese
itemsincluded educating patients and colleagues, applying nursing
research into practice and active participation in the development
of nursing in the workplace.
Conclusions. e results of this study indicate that postgraduate
qualifications and years of work experience within the same unit
influence the competence of surgical nurses. it is important to enable nurses in gaining postgraduate qualifications and ensure
availability of specialised training and education as the study results indicate that specialisation within nursing has increasedVísindasjóður félags íslenskra hjúkrunarfræðinga (B-hluti) og Vísindasjóður Landspítal