Now showing items 1-20 of 6881

    • Venovenous extracorporeal membrane oxygenation treatment in a low-volume and geographically isolated cardiothoracic centre.

      Ingvarsdottir, Inga L; Vidarsdottir, Halla; Valsson, Felix; Simonardottir, Liney; Sigurdsson, Martin I; Myrdal, Gunnar; Geirsson, Arnar; Gudbjartsson, Tomas; 1 Department of Anaesthesiology and Intensive Care, Landspitali University Hospital, Reykjavik, Iceland. 2 Cardiothoracic Surgery, Landspitali University Hospital, Reykjavik, Iceland. 3 Faculty of Medicine, University of Iceland, Reykjavik, Iceland. (Wiley, 2019-08)
      BACKGROUND: Extracorporeal membrane oxygenation (ECMO) treatment is generally offered in large tertiary cardiothoracic referral centres. Here we present the indications and outcome of venovenous-ECMO (VV-ECMO) treatment in a low-volume, geographically isolated single-centre in Iceland, a country of 350 000 inhabitants. Our hypothesis was that patient survival in such a centre can be similar to that at high-volume centres. METHODS: A retrospective study that included all patients treated with VV-ECMO in Iceland from 1991-2016 (n = 17). Information on demographics, indications and in-hospital survival was collected from patient charts and APACHE II and Murray scores were calculated. Information on long-term survival was collected from a centralized registry. RESULTS: Seventeen patients were treated with VV-ECMO (nine males, median age 33 years, range 14-74), the indication for 16 patients was severe acute respiratory distress syndrome, most often following pneumonia (n = 6), H1N1-infection (n = 3) or drowning (n = 2). Median APACHE-II and Murray-scores were 20 and 3.5, respectively, and median duration of VV-ECMO treatment was 9 days (range 2-40 days). In total 11 patients (64,7%) survived the treatment, with 10 patients (58,8%) surviving hospital discharge, all of who were still alive at long-term follow-up, with a median follow-up time of 9 years (August 15th, 2017). CONCLUSION: Venovenous-ECMO service can be provided in a low-volume and geographically isolated centre, like Iceland, with short- and long-term outcomes comparable to larger centres.
    • Infections and outcomes after cardiac surgery-The impact of outbreaks traced to transesophageal echocardiography probes.

      Vesteinsdottir, Edda; Helgason, Kristjan Orri; Sverrisson, Kristinn Orn; Gudlaugsson, Olafur; Karason, Sigurbergur; 1 Department of Anaesthesia and Intensive Care, Landspitali - The National University Hospital of Iceland, Reykjavik, Iceland. 2 Department of Clinical Microbiology, Landspitali - The National University Hospital of Iceland, Reykjavik, Iceland. 3 Department of Infectious Diseases, Landspitali - The National University Hospital of Iceland, Reykjavik, Iceland. 4 Faculty of Medicine, School of Health Sciences, University of Iceland, Reykjavik, Iceland. (Wiley, 2019-08)
      BACKGROUND: Infections are a frequent complication of cardiac surgery. The intraoperative use of transesophageal echocardiography (TEE) may be an underrecognized risk factor for post-operative infections. The aim of this study was to investigate infection rates and outcomes after cardiac surgery in a nationwide cohort, especially in relation to periods where surface damaged TEE probes were used. METHODS: This was a retrospective, observational study at Landspitali University Hospital. All consecutive cardiac surgery patients from 1 January 2013 to 31 December 2017 were included. Patients' charts were reviewed for evidence of infection, post-operative complications or death. RESULTS: During the study period, 973 patients underwent cardiac surgery at Landspitali and 198 (20.3%) developed a post-operative infection. The most common infections were: Pneumonia (9.1%), superficial surgical site (5.7%), bloodstream (2.8%) and deep sternal wound (1.7%). Risk factors for developing an infection included: The duration of procedure, age, insulin-dependent diabetes, EuroScore II, reoperation for bleeding and an operation in a period with a surface damaged TEE probe in use. Twenty-two patients were infected with a multidrug resistant strain of Klebsiella oxytoca, 10 patients with Pseudomonas aeruginosa and two patients developed endocarditis with Enterococcus faecalis. All three pathogens were cultured from the TEE probe in use at respective time, after decontamination. The 30-day mortality rate in the patient cohort was 3.2%. CONCLUSIONS: The intraoperative use of surface damaged TEE probes caused two serious infection outbreaks in patients after cardiac surgery. TEE probes need careful visual inspection during decontamination and probe sheaths are recommended.
    • Drug-Induced Liver Injury - Types and Phenotypes.

      Hoofnagle, Jay H; Björnsson, Einar S; [ 1 ] NIDDK, Liver Dis Res Branch, Div Digest Dis & Nutr, NIH, Bethesda, MD 20892 USA Show more [ 2 ] Natl Univ Hosp Iceland, Dept Internal Med, Reykjavik, Iceland Show more [ 3 ] Univ Iceland, Fac Med, Reykjavik, Iceland (Massachusetts Medical Society, 2019-07-18)
      The liver has a range of responses to drug-induced injury, with a number of phenotypes. In addition, idiosyncratic reactions may occur as a consequence of both direct drug action and indirect drug effects. Antibiotics are the most common cause of drug-induced liver injury.
    • Mendelian randomisation study of height and body mass index as modifiers of ovarian cancer risk in 22,588 BRCA1 and BRCA2 mutation carriers.

      Qian, Frank; Rookus, Matti A; Leslie, Goska; Risch, Harvey A; Greene, Mark H; Aalfs, Cora M; Adank, Muriel A; Adlard, Julian; Agnarsson, Bjarni A; Ahmed, Munaza; et al. (Nature Publishing Group, 2019-07)
      BACKGROUND: Height and body mass index (BMI) are associated with higher ovarian cancer risk in the general population, but whether such associations exist among BRCA1/2 mutation carriers is unknown. METHODS: We applied a Mendelian randomisation approach to examine height/BMI with ovarian cancer risk using the Consortium of Investigators for the Modifiers of BRCA1/2 (CIMBA) data set, comprising 14,676 BRCA1 and 7912 BRCA2 mutation carriers, with 2923 ovarian cancer cases. We created a height genetic score (height-GS) using 586 height-associated variants and a BMI genetic score (BMI-GS) using 93 BMI-associated variants. Associations were assessed using weighted Cox models. RESULTS: Observed height was not associated with ovarian cancer risk (hazard ratio [HR]: 1.07 per 10-cm increase in height, 95% confidence interval [CI]: 0.94-1.23). Height-GS showed similar results (HR = 1.02, 95% CI: 0.85-1.23). Higher BMI was significantly associated with increased risk in premenopausal women with HR = 1.25 (95% CI: 1.06-1.48) and HR = 1.59 (95% CI: 1.08-2.33) per 5-kg/m2 increase in observed and genetically determined BMI, respectively. No association was found for postmenopausal women. Interaction between menopausal status and BMI was significant (Pinteraction < 0.05). CONCLUSION: Our observation of a positive association between BMI and ovarian cancer risk in premenopausal BRCA1/2 mutation carriers is consistent with findings in the general population.
    • Resequencing Study Confirms That Host Defense and Cell Senescence Gene Variants Contribute to the Risk of Idiopathic Pulmonary Fibrosis.

      Moore, Camille; Blumhagen, Rachel Z; Yang, Ivana V; Walts, Avram; Powers, Julie; Walker, Tarik; Bishop, Makenna; Russell, Pamela; Vestal, Brian; Cardwell, Jonathan; et al. (American Thoracic Society, 2019-07-15)
      Rationale: Several common and rare genetic variants have been associated with idiopathic pulmonary fibrosis, a progressive fibrotic condition that is localized to the lung. Objectives: To develop an integrated understanding of the rare and common variants located in multiple loci that have been reported to contribute to the risk of disease. Methods: We performed deep targeted resequencing (3.69 Mb of DNA) in cases (n = 3,624) and control subjects (n = 4,442) across genes and regions previously associated with disease. We tested for associations between disease and 1) individual common variants via logistic regression and 2) groups of rare variants via sequence kernel association tests. Measurements and Main Results: Statistically significant common variant association signals occurred in all 10 of the regions chosen based on genome-wide association studies. The strongest risk variant is the MUC5B promoter variant rs35705950, with an odds ratio of 5.45 (95% confidence interval, 4.91-6.06) for one copy of the risk allele and 18.68 (95% confidence interval, 13.34-26.17) for two copies of the risk allele (P = 9.60 × 10-295). In addition to identifying for the first time that rare variation in FAM13A is associated with disease, we confirmed the role of rare variation in the TERT and RTEL1 gene regions in the risk of IPF, and found that the FAM13A and TERT regions have independent common and rare variant signals. Conclusions: A limited number of common and rare variants contribute to the risk of idiopathic pulmonary fibrosis in each of the resequencing regions, and these genetic variants focus on biological mechanisms of host defense and cell senescence.
    • Imaging Patterns Are Associated with Interstitial Lung Abnormality Progression and Mortality.

      Putman, Rachel K; Gudmundsson, Gunnar; Axelsson, Gisli Thor; Hida, Tomoyuki; Honda, Osamu; Araki, Tetsuro; Yanagawa, Masahiro; Nishino, Mizuki; Miller, Ezra R; Eiriksdottir, Gudny; et al. (American Thoracic Society, 2019-07-15)
      Rationale: Interstitial lung abnormalities (ILA) are radiologic abnormalities on chest computed tomography scans that have been associated with an early or mild form of pulmonary fibrosis. Although ILA have been associated with radiologic progression, it is not known if specific imaging patterns are associated with progression or risk of mortality. Objectives: To determine the role of imaging patterns on the risk of death and ILA progression. Methods: ILA (and imaging pattern) were assessed in 5,320 participants from the AGES-Reykjavik Study, and ILA progression was assessed in 3,167 participants. Multivariable logistic regression was used to assess factors associated with ILA progression, and Cox proportional hazards models were used to assess time to mortality. Measurements and Main Results: Over 5 years, 327 (10%) had ILA on at least one computed tomography, and 1,435 (45%) did not have ILA on either computed tomography. Of those with ILA, 238 (73%) had imaging progression, whereas 89 (27%) had stable to improved imaging; increasing age and copies of MUC5B genotype were associated with imaging progression. The definite fibrosis pattern was associated with the highest risk of progression (odds ratio, 8.4; 95% confidence interval, 2.7-25; P = 0.0003). Specific imaging patterns were also associated with an increased risk of death. After adjustment, both a probable usual interstitial pneumonia and usual interstitial pneumonia pattern were associated with an increased risk of death when compared with those indeterminate for usual interstitial pneumonia (hazard ratio, 1.7; 95% confidence interval, 1.2-2.4; P = 0.001; hazard ratio, 3.9; 95% confidence interval, 2.3-6.8;P < 0.0001), respectively. Conclusions: In those with ILA, imaging patterns can be used to help predict who is at the greatest risk of progression and early death.
    • Improving preparedness to respond to cross-border hepatitis A outbreaks in the European Union/European Economic Area: towards comparable sequencing of hepatitis A virus.

      Enkirch, Theresa; Severi, Ettore; Vennema, Harry; Thornton, Lelia; Dean, Jonathan; Borg, Maria-Louise; Ciccaglione, Anna Rita; Bruni, Roberto; Christova, Iva; Ngui, Siew Lin; et al. (European Centre for Disease Prevention and Control (ECDC), 2019-07)
      IntroductionSequence-based typing of hepatitis A virus (HAV) is important for outbreak detection, investigation and surveillance. In 2013, sequencing was central to resolving a large European Union (EU)-wide outbreak related to frozen berries. However, as the sequenced HAV genome regions were only partly comparable between countries, results were not always conclusive.AimThe objective was to gather information on HAV surveillance and sequencing in EU/European Economic Area (EEA) countries to find ways to harmonise their procedures, for improvement of cross-border outbreak responses.MethodsIn 2014, the European Centre for Disease Prevention and Control (ECDC) conducted a survey on HAV surveillance practices in EU/EEA countries. The survey enquired whether a referral system for confirming primary diagnostics of hepatitis A existed as well as a central collection/storage of hepatitis A cases' samples for typing. Questions on HAV sequencing procedures were also asked. Based on the results, an expert consultation proposed harmonised procedures for cross-border outbreak response, in particular regarding sequencing. In 2016, a follow-up survey assessed uptake of suggested methods.ResultsOf 31 EU/EEA countries, 23 (2014) and 27 (2016) participated. Numbers of countries with central collection and storage of HAV positive samples and of those performing sequencing increased from 12 to 15 and 12 to 14 respectively in 2016, with all countries typing an overlapping fragment of 218 nt. However, variation existed in the sequenced genomic regions and their lengths.ConclusionsWhile HAV sequences in EU/EEA countries are comparable for surveillance, collaboration in sharing and comparing these can be further strengthened.
    • The extent to which adequacy of staffing predicts nursing teamwork in hospitals.

      Bragadóttir, Helga; Kalisch, Beatrice J; Bergthóra Tryggvadóttir, Gudný; 1 Faculty of Nursing, School of Health Sciences, University of Iceland, Reykjavik, Iceland. 2 Landspitali University Hospital, Reykjavik, Iceland. 3 School of Nursing, University of Michigan, Ann Arbor, MI, USA. 4 The Social Science Research Institute, University of Iceland, Reykjavik, Iceland. (Wiley, 2019-06-26)
      AIMS AND OBJECTIVES: The purpose of this study was to examine the extent to which staffing adequacy predicts nursing teamwork, controlling for demographic and background variables. BACKGROUND: Findings from former studies indicate that hospital, unit and staff characteristics may be related to nursing teamwork, such as type of hospital and unit, role, gender, age, work experience, type of shift worked, shift length, number of working hours per week, overtime and staffing adequacy. Teamwork as well as staffing is identified as significant contributors to patient and staff safety in hospitals. However, the contribution of staffing to the quality of nursing teamwork is scarcely studied. DESIGN: This was a quantitative descriptive cross-sectional study using the paper-and-pencil questionnaire Nursing Teamwork Survey-Icelandic. METHODS: The study was conducted in 27 inpatient units in eight hospitals in Iceland with a sample of 925 nursing staff members. Participants were 567 registered nurses, practical nurses, unit secretaries and nurse unit managers. The Strengthening the Reporting of Observational Studies in Epidemiology checklist was used for this paper. RESULTS: When controlling for unit type, role, experience on current unit and intent to leave, perceived adequacy of staffing alone explains up to 10% of overall teamwork. Unit type, role, years of experience on current unit and perceived staffing adequacy correlated significantly with overall teamwork. CONCLUSIONS: The findings of this study indicate that unit and staff characteristics, including perceived adequacy of staffing, are associated with and explain the variability in nursing teamwork on inpatient hospital units. The findings of this study provide important information for clinical nurses, nurse managers, policymakers and instructors in health care. RELEVANCE TO CLINICAL PRACTICE: The findings underline the importance of adequate staffing for nursing teamwork in inpatient hospital units.
    • Acute lower gastrointestinal bleeding: A population-based five-year follow-up study

      Hreinsson, Johann P; Ægisdottir, Silja; Bjornsson, Einar S; [ 1 ] Natl Univ Hosp Reykjavik, Dept Internal Med, Sect Gastroenterol & Hepatol, Reykjavik, Iceland Show more [ 2 ] Univ Iceland, Fac Med, Reykjavik, Iceland (Sage Publications, 2019-07)
      Background Data on the natural history of acute lower gastrointestinal bleeding (ALGIB) are lacking. We evaluated five-year bleeding risk and mortality in ALGIB patients and controls. Furthermore, we aimed to find predictors of rebleeding. Methods This was a population-based retrospective case-control study conducted at the National University Hospital of Iceland, and included every individual who underwent endoscopy in 2010-2011. ALGIB was defined as rectal bleeding leading to hospitalisation or occurring in a hospitalised patient. Controls were randomly selected from those who underwent endoscopy in the same time period but who did not have GIB, and were matched for sex and age. Patients were followed up five years after index bleeding. Rebleeding was defined as ALGIB >14 days after index bleeding. Results In total, 2294 patients underwent 2602 colonoscopies in 2010-2011. Of those, 319 (14%) had ALGIB. The mean age for cases and controls was 64 and 65 years (+/- 19.3-20.7), respectively, and females accounted for 51-52% of the study population. For ALGIB patients, the five-year risk of a bleeding was 20% (95% confidence interval (CI) 15-24%) compared to 3% (95% CI 1-5%) in controls (log rank < 0.0001; co-morbidity-adjusted hazard ratio (HR) 6.9 (95% CI 3.4-14)). Only 37% of bleeders had the same cause of index bleeding and rebleeding. In ALGIB patients, age and inflammatory bowel disease (IBD) were predictors of rebleeding, with odds ratios per 10 years of 1.3 (95% CI 1.1-1.6) and 4.3 (95% CI 1.5-12), respectively. Bleeders did not have a higher risk of five-year mortality compared to controls (HR = 1.2; 95% CI 0.87-1.6). Conclusions One fifth of ALGIB patients had rebleeding during follow-up. Age and IBD were independent predictors of rebleeding. ALGIB was not associated with lower five-year survival.
    • Red blood cell utilization and transfusion triggers in patients diagnosed with chronic lymphocytic leukaemia in Iceland 2003-2016.

      Thorvaldsson, Hrafn Hliddal; Vidarsson, Brynjar; Sveinsdottir, Signy Vala; Olafsson, Gunnar Bjorn; Halldorsdottir, Anna Margret; 1 Faculty of Medicine, University of Iceland, Reykjavik, Iceland. 2 Department of Hematology, Landspitali National University Hospital of Iceland, Reykjavik, Iceland. 3 Blood Bank, Landspitali National University Hospital of Iceland, Reykjavik, Iceland. (Wiley, 2019-07)
      BACKGROUND AND OBJECTIVES: Revised Icelandic guidelines proposed a restrictive haemoglobin (Hb) threshold of 70 g/l for red blood cell (RBC) transfusions in general, but 100 g/l for malignancies/bone marrow suppression. Chronic lymphocytic leukaemia (CLL) is frequently complicated by anaemia. The objective was to investigate RBC transfusion practices in CLL. MATERIALS AND METHODS: This retrospective nation-wide study utilized an Icelandic registry of CLL patients diagnosed between 2003 and 2016. Medical records were reviewed and haemoglobin transfusion triggers compared for two periods: Earlier (2003-2012) and latter (2013-2017). RESULTS: Two hundred and thirteen patients were diagnosed with CLL over the period whereof 77 (36·2%) received RBC transfusion(s). Median time from diagnosis to first transfusion was 2·2 years. Higher age, Rai stage 3/4 at diagnosis (P < 0·05) and chemotherapy (P < 0·001) were associated with increased odds of transfusions. Shorter time to first transfusion correlated with higher age (P < 0·001) and Rai stage (P = 0·02) at diagnosis. The mean Hb trigger was 90·4 and 81·2 in the earlier and latter period respectively (P = 0·01). This difference in Hb triggers was most pronounced in patients without documented bone marrow involvement, or 80·5 g/l compared to 93·5 g/l (P = 0·004). The median time from diagnosis to transfusion was longer in the latter period (2·9 years vs. 1·6 years, P = 0·01). After RBC transfusions the survival decreased significantly (P < 0·001). CONCLUSION: One-third of CLL patients received RBC transfusions but few were heavily transfused. Older age, Rai stage, and chemotherapy predicted RBC use. The Hb transfusion trigger decreased over time while time to first RBC transfusion increased. RBC transfusions predict poor survival.
    • Intermittent Versus Continuous PEG-Asparaginase to Reduce Asparaginase-Associated Toxicities: A NOPHO ALL2008 Randomized Study.

      Albertsen, Birgitte Klug; Grell, Kathrine; Abrahamsson, Jonas; Lund, Bendik; Vettenranta, Kim; Jónsson, Ólafur G; Frandsen, Thomas L; Wolthers, Benjamin O; Heyman, Mats; Schmiegelow, Kjeld; et al. (American Society of Clinical Oncology, 2019-07)
      PURPOSE: Asparaginase is an essential drug in childhood acute lymphoblastic leukemia (ALL) therapy and is frequently given for months to obtain continuous asparagine depletion. We randomly assigned patients to continuous versus intermittent pegylated-asparaginase (PEG-asp) treatment, hypothesizing there would be decreased toxicity with unchanged efficacy. METHODS: Children (median age, 4.2 years) treated for non-high-risk ALL according to the Nordic Society for Pediatric Hematology and Oncology ALL2008 protocol received five intramuscular PEG-asp injections (1,000 IU/m2) every two weeks and were then randomly assigned to additional three doses (6-week intervals [experimental arm], n = 309) versus 10 doses (2-week intervals [standard arm], n = 316). The primary end point was noninferior (6% margin) disease-free survival. Toxicity reduction was a secondary end point. Occurrence of asparaginase-associated hypersensitivity, pancreatitis, osteonecrosis, and thromboembolism were prospectively registered. RESULTS: After a median follow-up of 4.1 years, the 5-year disease-free survival was 92.2% (95% CI, 88.6 to 95.8) and 90.8% (95% CI, 87.0 to 94.6) in the experimental and standard arms, respectively. The 3-year cumulative incidence of any first asparaginase-associated toxicity (hypersensitivity [n = 13]; osteonecrosis [n = 29]; pancreatitis [n = 24]; thromboembolism [n = 17]) was 9.3% in the experimental arm and 18.1% in the standard arm (P = .001). Asparaginase-associated toxicity reduction was confirmed in sex- and risk-group-adjusted Cox regression analysis stratified by age (≥ 10 and < 10 years; hazard ratio, 0.48; P = .001). The experimental arm had the lowest incidences of all four toxicities, reaching significance for pancreatitis (6-month risk, 5.8% v 1.3%; P = .002). CONCLUSION: The excellent cure rates and reduced toxicity risk support the use of intermittent PEG-asp therapy after the first 10 weeks in future childhood ALL trials that apply prolonged PEG-asp therapy.
    • Determinants of fractional exhaled nitric oxide in healthy men and women from the European Community Respiratory Health Survey III.

      Nerpin, Elisabet; Olivieri, Mario; Gislason, Thorainn; Olin, Anna C; Nielsen, Rune; Johannessen, Ane; Ferreira, Diogenes S; Marcon, Alessandro; Cazzoletti, Lucia; Accordini, Simone; et al. (Wiley, 2019-07)
      INTRODUCTION: The fractional exhaled nitric oxide (FE NO) is a marker for type 2 inflammation used in diagnostics and management of asthma. In order to use FE NO as a reliable biomarker, it is important to investigate factors that influence FE NO in healthy individuals. Men have higher levels of FE NO than women, but it is unclear whether determinants of FE NO differ by sex. OBJECTIVE: To identify determinants of FE NO in men and women without lung diseases. METHOD: Fractional exhaled nitric oxide was validly measured in 3881 healthy subjects that had answered the main questionnaire of the European Community Respiratory Health Survey III without airways or lung disease. RESULTS: Exhaled NO levels were 21.3% higher in men compared with women P < 0.001. Being in the upper age quartile (60.3-67.6 years), men had 19.2 ppb (95% CI: 18.3, 20.2) higher FE NO than subjects in the lowest age quartile (39.7-48.3 years) P = 0.02. Women in the two highest age quartiles (54.6-60.2 and 60.3-67.6 years) had 15.4 ppb (14.7, 16.2), P = 0.03 and 16.4 ppb (15.6, 17.1), P = <0.001 higher FE NO, compared with the lowest age quartile. Height was related to 8% higher FE NO level in men (P < 0.001) and 5% higher FE NO levels in women (P = 0.008). Men who smoked had 37% lower FE NO levels and women had 30% lower levels compared with never-smokers (P < 0.001 for both). Men and women sensitized to both grass and perennial allergens had higher FE NO levels compared with non-sensitized subjects 26% and 29%, P < 0.001 for both. CONCLUSION AND CLINICAL RELEVANCE: Fractional exhaled nitric oxide levels were higher in men than women. Similar effects of current smoking, height, and IgE sensitization were found in both sexes. FE NO started increasing at lower age in women than in men, suggesting that interpretation of FE NO levels in adults aged over 50 years should take into account age and sex.
    • The Forensic Pathology of Fatal Attacks by the Large Mammals Inhabiting the Nordic Wilderness-A Literature Review.

      Gudmannsson, Petur; Berge, Johan; 1 Department of Forensic Pathology, Landspitali University Hospital, 101, Reykjavik, Iceland. 2 University of Iceland, Faculty of Medicine, Vatnsmýrarvegur 16, 101, Reykjavik, Iceland. 3 The Swedish National Board of Forensic Medicine, The Division for Forensic Medicine, Artillerigatan 12, 58758, Linköping, Sweden. (Wiley, 2019-07)
      Fatalities due to animal attacks are rare in forensic medical work but have been known to pose problems due to their potential to mimic homicide. This review summarizes reported cases of fatal attacks by large mammals that inhabit the Nordic wilderness, namely brown bear, moose, wild boar, and wolf, and attempts to elucidate injury patterns that can guide the forensic pathologist to identifying the species and modus operandi of the attacker. A tendency toward a species-specific injury pattern was observed. Injuries by bear and especially wolf are dominated by biting whereas moose and wild boar do not seem to bite their victims. The bear uses its paws, both for hitting, resulting in crush injury and fractures, and clawing with resulting excoriations and possible penetrating injuries. Crush injuries and fractures appear, on the other hand, to be minimal or absent in attacks by wolf and wild boar.
    • Injury potential of one-litre beer steins.

      Adamec, J; Dorfner, Petra; Graw, M; Lochner, S; Kunz, S N; 1 Institute of Forensic Medicine, Ludwigs-Maximilians University Munich, Nussbaumst. 26, 80336, Munich, Germany. 2 Institute of Forensic Medicine, Ludwigs-Maximilians University Munich, Nussbaumst. 26, 80336, Munich, Germany. 3 Department of Forensic Pathology, Landspítali University Hospital Reykjavik, Reykjavík, Iceland. (Springer, 2019-07)
      Injuries resulting from blows with beer steins are a frequent occurrence during annual autumn fairs or at beer halls in South Germany and Austria. The majority of these cases are tried in court and thus being assessed by a forensic medicine expert. The article at hand gives a short overview on the injury potential of one-litre beer steins and explains the key variables to consider when analyzing beer stein injuries. On the basis of representative cases, which were assessed by specialists from the Institute of Legal Medicine of the Munich University over the last 5 years, the main biomechanical aspects and resulting injuries of one-litre beer stein assaults are discussed. Several severe and potentially life-threatening injuries have been observed after an assault with a one-litre beer stein. There is a discrepancy between the mechanical stability of brand new and used steins and the corresponding injuries, which can be explained by a decrease in impact tolerance of the steins with their use. In general, a blow with a one-litre glass or stonework beer stein to the head can cause severe and even life-threatening blunt as well as sharp trauma injuries.
    • Drug-Induced Liver Injury due to Flucloxacillin: Relevance of Multiple Human Leukocyte Antigen Alleles.

      Nicoletti, Paola; Aithal, Guruprasad P; Chamberlain, Thomas C; Coulthard, Sally; Alshabeeb, Mohammad; Grove, Jane I; Andrade, Raul J; Bjornsson, Einar; Dillon, John F; Hallberg, Par; et al. (Wiley, 2019-07)
      Some patients prescribed flucloxacillin (~ 0.01%) develop drug-induced liver injury (DILI). HLA-B*57:01 is an established genetic risk factor for flucloxacillin DILI. To consolidate this finding, identify additional genetic factors, and assess relevance of risk factors for flucloxacillin DILI in relation to DILI due to other penicillins, we performed a genomewide association study involving 197 flucloxacillin DILI cases and 6,835 controls. We imputed single-nucleotide polymorphism and human leukocyte antigen (HLA) genotypes. HLA-B*57:01 was the major risk factor (allelic odds ratio (OR) = 36.62; P = 2.67 × 10-97 ). HLA-B*57:03 also showed an association (OR = 79.21; P = 1.2 × 10-6 ). Within the HLA-B protein sequence, imputation showed valine97 , common to HLA-B*57:01 and HLA-B*57:03, had the largest effect (OR = 38.1; P = 9.7 × 10-97 ). We found no HLA-B*57 association with DILI due to other isoxazolyl penicillins (n = 6) or amoxicillin (n = 15) and no significant non-HLA signals for any penicillin-related DILI.
    • Food Allergy in Adults: Substantial Variation in Prevalence and Causative Foods Across Europe.

      Lyons, Sarah A; Burney, Peter G J; Ballmer-Weber, Barbara K; Fernandez-Rivas, Montserrat; Barreales, Laura; Clausen, Michael; Dubakiene, Ruta; Fernandez-Perez, Cristina; Fritsche, Philipp; Jedrzejczak-Czechowicz, Monika; et al. (Elsevier Science, 2019-07)
      BACKGROUND: According to the community-based EuroPrevall surveys, prevalence of self-reported food allergy (FA) in adults across Europe ranges from 2% to 37% for any food and 1% to 19% for 24 selected foods. OBJECTIVE: To determine the prevalence of probable FA (symptoms plus specific IgE-sensitization) and challenge-confirmed FA in European adults, along with symptoms and causative foods. METHODS: In phase I of the EuroPrevall project, a screening questionnaire was sent to a random sample of the general adult population in 8 European centers. Phase II consisted of an extensive questionnaire on reactions to 24 preselected commonly implicated foods, and measurement of specific IgE levels. Multiple imputation was performed to estimate missing symptom and serology information for nonresponders. In the final phase, subjects with probable FA were invited for double-blind placebo-controlled food challenge. RESULTS: Prevalence of probable FA in adults in Athens, Reykjavik, Utrecht, Lodz, Madrid, and Zurich was respectively 0.3%, 1.4%, 2.1%, 2.8%, 3.3%, and 5.6%. Oral allergy symptoms were reported most frequently (81.6%), followed by skin symptoms (38.2%) and rhinoconjunctivitis (29.5%). Hazelnut, peach, and apple were the most common causative foods in Lodz, Utrecht, and Zurich. Peach was also among the top 3 causative foods in Athens and Madrid. Shrimp and fish allergies were relatively common in Madrid and Reykjavik. Of the 55 food challenges performed, 72.8% were classified as positive. CONCLUSIONS: FA shows substantial geographical variation in prevalence and causative foods across Europe. Although probable FA is less common than self-reported FA, prevalence still reaches almost 6% in parts of Europe.
    • Use of combined hormonal contraceptives among women with systemic lupus erythematosus with and without medical contraindications to oestrogen.

      Mendel, Arielle; Bernatsky, Sasha; Pineau, Christian A; St-Pierre, Yvan; Hanly, John G; Urowitz, Murray B; Clarke, Ann E; Romero-Diaz, Juanita; Gordon, Caroline; Bae, Sang-Cheol; et al. (Læknafélag Íslands, Læknafélag Reykjavíkur, 2019-07)
      OBJECTIVES: To assess the prevalence of combined hormonal contraceptives (CHCs) in reproductive-age women with SLE with and without possible contraindications and to determine factors associated with their use in the presence of possible contraindications. METHODS: This observational cohort study included premenopausal women ages 18-45 years enrolled in the SLICC Registry ⩽15 months after SLE onset, with annual assessments spanning 2000-2017. World Health Organization Category 3 or 4 contraindications to CHCs (e.g. hypertension, aPL) were assessed at each study visit. High disease activity (SLEDAI score >12 or use of >0.5 mg/kg/day of prednisone) was considered a relative contraindication. RESULTS: A total of 927 SLE women contributed 6315 visits, of which 3811 (60%) occurred in the presence of one or more possible contraindication to CHCs. Women used CHCs during 512 (8%) visits, of which 281 (55%) took place in the setting of one or more possible contraindication. The most frequently observed contraindications were aPL (52%), hypertension (34%) and migraine with aura (22%). Women with one or more contraindication were slightly less likely to be taking CHCs [7% of visits (95% CI 7, 8)] than women with no contraindications [9% (95% CI 8, 10)]. CONCLUSION: CHC use was low compared with general population estimates (>35%) and more than half of CHC users had at least one possible contraindication. Many yet unmeasured factors, including patient preferences, may have contributed to these observations. Further work should also aim to clarify outcomes associated with this exposure.
    • T cell receptor gene therapy targeting WT1 prevents acute myeloid leukemia relapse post-transplant.

      Chapuis, Aude G; Egan, Daniel N; Bar, Merav; Schmitt, Thomas M; McAfee, Megan S; Paulson, Kelly G; Voillet, Valentin; Gottardo, Raphael; Ragnarsson, Gunnar B; Bleakley, Marie; et al. (Nature Publishing Group, 2019-07)
      Relapse after allogeneic hematopoietic cell transplantation (HCT) is the leading cause of death in patients with acute myeloid leukemia (AML) entering HCT with poor-risk features1-3. When HCT does produce prolonged relapse-free survival, it commonly reflects graft-versus-leukemia effects mediated by donor T cells reactive with antigens on leukemic cells4. As graft T cells have not been selected for leukemia specificity and frequently recognize proteins expressed by many normal host tissues, graft-versus-leukemia effects are often accompanied by morbidity and mortality from graft-versus-host disease5. Thus, AML relapse risk might be more effectively reduced with T cells expressing receptors (TCRs) that target selected AML antigens6. We therefore isolated a high-affinity Wilms' Tumor Antigen 1-specific TCR (TCRC4) from HLA-A2+ normal donor repertoires, inserted TCRC4 into Epstein-Bar virus-specific donor CD8+ T cells (TTCR-C4) to minimize graft-versus-host disease risk and enhance transferred T cell survival7,8, and infused these cells prophylactically post-HCT into 12 patients ( NCT01640301 ). Relapse-free survival was 100% at a median of 44 months following infusion, while a concurrent comparative group of 88 patients with similar risk AML had 54% relapse-free survival (P = 0.002). TTCR-C4 maintained TCRC4 expression, persisted long-term and were polyfunctional. This strategy appears promising for preventing AML recurrence in individuals at increased risk of post-HCT relapse.
    • Nárakviðslit – yfirlitsgrein

      Marta Rós Berndsen; Tómas Guðbjartsson; Fritz H. Berndsen; 1 Sahlgrenska háskólasjúkrahúsið í Gautaborg, Svíþjóð, 2 skurðsviði Landspítala, 3 læknadeild Háskóla Íslands, 4 handlækningadeild Heilbrigðisstofnunar Vesturlands, Akranesi. (Læknafélag Íslands, Læknafélag Reykjavíkur, 2019-09)
      Nárakviðslit eru algengust kviðslita og eru 90% sjúklinganna karlmenn en þriðjungur karla greinist einhvern tíma á ævinni með slíkt kviðslit. Algengast er að kviðslit greinist hjá börnum og eftir miðjan aldur, oftast vegna fyrirferðar og verkja á nárasvæði en í einstaka ­tilfellum í kjölfar garnastíflu. Skurðaðgerð er eina læknandi meðferðin við nárakviðsliti og er hún ein algengasta aðgerð sem framkvæmd er. Aðgerðin er oftast gerð sem valaðgerð annaðhvort í staðdeyfingu, mænudeyfingu eða svæfingu. Þá er bakveggur nárans styrktur, oftast með neti, og er bæði hægt að gera aðgerðina opið að framanverðu eða að innanverðu með holsjáraðgerð. Helstu vandamál eftir aðgerð eru endurtekin kviðslit og langvarandi verkir en með notkun neta og betri aðgerðartækni hefur tíðni endurtekinna kviðslita lækkað umtalsvert. Í þessari yfirlitsgrein er fjallað um tíðni, orsakir og meðferð nárakviðslita með áherslu á nýjungar í skurðmeðferð.
    • Algengi svefntruflana hjá fólki með MS

      Aðalbjörg Albertsdóttir; Árún K. Sigurðardóttir; Björg Þorleifsdóttir; 1 Taugasviði Reykjalundar, 2 heilbrigðisvísindasviði Háskólans á Akureyri, 3 Sjúkrahúsinu á Akureyri, 4 Lífeðlisfræðistofnun læknadeildar Háskóla Íslands (Læknafélag Íslands, Læknafélag Reykjavíkur, 2019-09)
      INNGANGUR Samkvæmt erlendum rannsóknum eru svefntruflanir hjá fólki með MS algengar, stórlega vangreindar og hafa áhrif á heilsu. Tilgangur rannsóknarinnar var að afla upplýsinga um algengi skertra svefngæða og helstu svefntruflana hjá MS-greindum á Íslandi. AÐFERÐ Lýsandi þversniðsrannsókn. Þýðið var MS-greindir á Íslandi og úrtakið MS-greindir sem voru á netpóstlista MS-félagsins og/eða höfðu aðgang að Facebook-síðu MS-félagsins. Rafrænn spurningalisti með fjórum matskvörðum og bakgrunnsbreytum, auk spurninga um greinda svefnsjúkdóma, var útbúinn og starfsfólk MS-félagsins sendi vefslóðina á úrtakið. Matskvarðar: Svefngæðakvarðinn (Pittsburgh- Sleep-Quality-Index; PSQI), Svefnleysiskvarðinn (Insomnia-Severity-Index; ISI), STOP-Bang-spurningalistinn og greiningarskilmerki fótaóeirðar. Með matskvörðum og stökum spurningum var skimað fyrir algengi skertra svefngæða og algengi 7 mismunandi þátta sem geta truflað svefn. Gögn voru greind með lýsandi og greinandi tölfræði og SPSS-útgáfa 25 var notuð við tölfræðiútreikninga. NIÐURSTÖÐUR Tæp 40% MS-greindra á Íslandi tóku þátt. Þátttakendur voru 234, meðalaldur var 47 ár (aldursbil 20-92 ára) og 77% voru konur. Algengi skertra svefngæða (>5 stig á PSQI) var 68%. Fjórir algengustu þættirnir sem trufluðu svefn voru: salernisferðir (39%), verkir (37%), einkenni svefnleysis (30%) og einkenni kæfisvefns (24%). Í ljós kom að 79% þátttakenda höfðu minnst eina svefntruflun og að meðaltali höfðu þátttakendur tæpar tvær svefntruflanir hver. Einkenni svefnleysis höfðu sterk tengsl við lítil svefngæði. ÁLYKTANIR Bregðast þarf við hárri tíðni skertra svefngæða og svefntruflana hjá MS-greindum. PSQI getur gagnast við mat á svefngæðum og gefið vísbendingar um hvað þarfnast nánari skoðunar. Til að auka svefngæði MS-greindra almennt ætti sérstaklega að horfa til greiningar og meðferðar á svefnleysi.