• Profiling inflammatory response in lesions of cutaneous leishmaniasis patients using a non-invasive sampling method combined with a high-throughput protein detection assay

      Taslimi, Yasaman; Agbajogu, Christopher; Brynjolfsson, Siggeir Fannar; Masoudzadeh, Nasrin; Mashayekhi, Vahid; Gharibzadeh, Safoora; Östensson, Malin; Nakka, Sravya Sowdamini; Mizbani, Amir; Rafati, Sima; et al. (Elsevier Science, 2020-06-01)
      Background: Cutaneous leishmaniasis (CL) is an infection caused by Leishmania (L.) protozoa transmitted through the bite of infected sand fly. Previously, invasive sampling of blood and skin along with low throughput methods were used for determination of inflammatory response in CL patients. Aims/methodology: We established a novel approach based on a non-invasive adhesive tape-disc sampling combined with a powerful multiplexing technique called proximity extension assay for profiling 92 inflammatory cytokines, chemokines and surface molecules in the lesions of CL patients infected with L. tropica. Sample collection was done non-invasively by using adhesive tape-discs from lesion and normal skin of 33 L. tropica positive patients. Results: Out of 92 inflammatory proteins, the level of 34 proteins was significantly increased in the lesions of CL patients compared to their normal skin. This includes the chemokines CCL2, CCL3, CCL4, CXCL1, CXCL5, CXCL9, CXCL10 and CXCL11, together with the interleukins IL-6, IL-8, IL-18, LIF and OSM. The remaining significantly changed inflammatory proteins include 7 surface molecules and receptors: CD5, CD40, CDCP1, 4E-BP1, TNFRSF9, IL-18R1 and OPG as well as 16 other cytokines and proteins: MMP-1, CSF-1, VEGFA, uPA, EN-RAGE, LAP TGF-β1, HGF, MMP-10, CASP-8, TNFSF14, STAMPB, ADA, TRAIL and ST1A1. Further, 13 proteins showed an increasing trend, albeit not statistically significant, in the CL lesions, including TGF-α, CCL23, MCP-2, IL-12B, CXCL6, IL-24, FGF-19, TNFβ, CD6, TRANCE, IL10, SIR2 and CCL20. Conclusion: We herein report a novel approach based on a non-invasive sampling method combined with the high-throughput protein assay for profiling inflammatory proteins in CL lesions. Using this approach, we could profile inflammatory proteins in the lesions from CL patients. This new non-invasive approach may have implications for studying skin inflammatory mediators in CL and other skin disorders.
    • Are conventional stone analysis techniques reliable for the identification of 2,8-dihydroxyadenine kidney stones? A case series.

      Runolfsdottir, Hrafnhildur L; Lin, Tzu-Ling; Goldfarb, David S; Sayer, John A; Michael, Mini; Ketteridge, David; Rich, Peter R; Edvardsson, Vidar O; Palsson, Runolfur; 1Faculty of Medicine, School of Health Sciences, University of Iceland, Reykjavik, Iceland. 2Internal Medicine Services, Landspitali-The National University Hospital of Iceland, Reykjavik, Iceland. 3Department of Renal Medicine, University College London, London, UK. 4Nephrology Section, VA New York Harbor Healthcare System, and Division of Nephrology, New York University Langone Medical Center, New York, NY, USA. 5Renal Services, The Newcastle Hospitals NHS Foundation Trust, Newcastle upon Tyne, UK. 6Institute of Genetic Medicine, Newcastle University, Newcastle upon Tyne, UK. 7NIHR Newcastle Biomedical Research Centre, Newcastle upon Tyne, UK. 8Renal Section, Department of Pediatrics, Texas Children's Hospital, and Baylor College of Medicine, Houston, TX, USA. 9Department of Genetics and Molecular Pathology, Women's and Children's Hospital, Adelaide, Australia. 10Department of Structural and Molecular Biology, University College London, London, UK. 11Faculty of Medicine, School of Health Sciences, University of Iceland, Reykjavik, Iceland. vidare@lsh.is. 12Children's Medical Center, Landspitali-The National University Hospital of Iceland, Hringbraut, 101, Reykjavik, Iceland. vidare@lsh.is. 13Faculty of Medicine, School of Health Sciences, University of Iceland, Reykjavik, Iceland. runolfur@landspitali.is. 14Division of Nephrology, Landspitali-The National University Hospital of Iceland, Hringbraut, 101, Reykjavik, Iceland. runolfur@landspitali.is. (Springer, 2020-05-12)
      We have recently encountered patients incorrectly diagnosed with adenine phosphoribosyltransferase (APRT) deficiency due to misidentification of kidney stones as 2,8-dihydroxyadenine (DHA) stones. The objective of this study was to examine the accuracy of stone analysis for identification of DHA. Medical records of patients referred to the APRT Deficiency Research Program of the Rare Kidney Stone Consortium in 2010-2018 with a diagnosis of APRT deficiency based on kidney stone analysis were reviewed. The diagnosis was verified by measurement of APRT enzyme activity or genetic testing. Attenuated total reflection-Fourier transform infrared (ATR-FTIR) spectra of pure crystalline DHA and a kidney stone obtained from one of the confirmed APRT deficiency cases were generated. The ATR-FTIR spectrum of the kidney stone matched the crystalline DHA spectrum and was used for comparison with available infrared spectra of stone samples from the patients. Of 17 patients referred, 14 had sufficient data available to be included in the study. In all 14 cases, the stone analysis had been performed by FTIR spectroscopy. The diagnosis of APRT deficiency was confirmed in seven cases and rejected in the remaining seven cases. Comparison of the ATR-FTIR spectrum of the DHA stone with the FTIR spectra from three patients who did not have APRT deficiency showed no indication of DHA as a stone component. Misidentification of DHA as a kidney stone component by clinical laboratories appears common among patients referred to our program. Since current clinical protocols used to interpret infrared spectra for stone analysis cannot be considered reliable for the identification of DHA stones, the diagnosis of APRT deficiency must be confirmed by other methods. Keywords: APRT deficiency; Infrared spectroscopy; Kidney stone composition; Misdiagnosis; Nephrolithiasis.
    • Feasibility and accuracy of a robotic guidance system for navigated spine surgery in a hybrid operating room: a cadaver study.

      Burström, Gustav; Balicki, Marcin; Patriciu, Alexandru; Kyne, Sean; Popovic, Aleksandra; Holthuizen, Ronald; Homan, Robert; Skulason, Halldor; Persson, Oscar; Edström, Erik; et al. (Nature Publishing Group, 2020-05-05)
      The combination of navigation and robotics in spine surgery has the potential to accurately identify and maintain bone entry position and planned trajectory. The goal of this study was to examine the feasibility, accuracy and efficacy of a new robot-guided system for semi-automated, minimally invasive, pedicle screw placement. A custom robotic arm was integrated into a hybrid operating room (OR) equipped with an augmented reality surgical navigation system (ARSN). The robot was mounted on the OR-table and used to assist in placing Jamshidi needles in 113 pedicles in four cadavers. The ARSN system was used for planning screw paths and directing the robot. The robot arm autonomously aligned with the planned screw trajectory, and the surgeon inserted the Jamshidi needle into the pedicle. Accuracy measurements were performed on verification cone beam computed tomographies with the planned paths superimposed. To provide a clinical grading according to the Gertzbein scale, pedicle screw diameters were simulated on the placed Jamshidi needles. A technical accuracy at bone entry point of 0.48 ± 0.44 mm and 0.68 ± 0.58 mm was achieved in the axial and sagittal views, respectively. The corresponding angular errors were 0.94 ± 0.83° and 0.87 ± 0.82°. The accuracy was statistically superior (p < 0.001) to ARSN without robotic assistance. Simulated pedicle screw grading resulted in a clinical accuracy of 100%. This study demonstrates that the use of a semi-automated surgical robot for pedicle screw placement provides an accuracy well above what is clinically acceptable.
    • Reoperation for bleeding following coronary artery bypass surgery with special focus on long-term outcomes.

      Marteinsson, Steinthor A; Heimisdóttir, Alexandra A; Axelsson, Tomas A; Johannesdottir, Hera; Arnadottir, Linda O; Gardarsdottir, Helga R; Johnsen, Arni; Sigurdsson, Martin I; Helgadottir, Solveig; Gudbjartsson, Tomas; et al. (Taylor & Francis, 2020-04-30)
      Objectives: We studied the incidence and risk factors of reoperation for bleeding following CABG in a nationwide cohort with focus on long-term complications and survival. Design: A retrospective study on 2060 consecutive, isolated CABG patients operated 2001-2016. Outcome of reoperated patients (n = 130) were compared to non-reoperated ones (n = 1930), including major adverse cardiac and cerebrovascular events (MACCE) and overall survival. Risk factors for reoperation were determined using multivariate logistic regression and a Cox proportional hazards model to assess prognostic factors of long-term survival. Median follow-up was 7.6 years. Results: One hundred thirty patients (6.3%) were reoperated with an annual decrease of 4.1% per year over the study period (p=.04). Major complications (18.5 vs. 9.6%) and 30-day mortality (8.5 vs. 1.9%,) were higher in the reoperation group (p<.001). The use of clopidogrel preoperatively (OR 3.62, 95% CI: 1.90-6.57) and reduced left ventricular ejection fraction (OR 2.23, 95% CI: 1.25-3.77) were the strongest predictors of reoperation, whereas off-pump surgery was associated with a lower reoperation risk (OR 0.44, 95% CI: 0.22-0.85). After exluding patients that died within 30 days postoperatively, no difference in long-term survival or freedom from MACCE was found between groups, and reoperation was not an independent risk factor for long-term mortality in multivariate analysis. Conclusions: The reoperation rate in this study was relatively high but decreased significantly over time. Reoperation was associated with twofold increased risk for major complications and fourfold 30-day mortality, but comparable long-term MACCE and survival rates. This implies that if patients survive the first 30 days following reoperation, their long-term outcome is comparable to non-reoperated patients.
    • Leukocyte nadir as a predictive factor for efficacy of adjuvant chemotherapy in breast cancer. Results from the prospective trial SBG 2000-1.

      Poikonen-Saksela, Paula; Lindman, Henrik; Sverrisdottir, Asgerdur; Edlund, Per; Villman, Kenneth; Tennvall Nittby, Lena; Cold, Søren; Bechmann, Troels; Stenbygaard, Lars; Ejlertsen, Bent; et al. (Taylor & Francis, 2020-04-29)
      Background: Retrospective studies have suggested that chemotherapy-induced leukopenia is associated with improved recurrence-free or overall survival. The SBG 2000-1 trial was designed to verify the favorable prognosis associated with chemotherapy-induced leukopenia in early breast cancer. Patients not experiencing chemotherapy-induced leukopenia were randomized into standard dosed or individually escalated chemotherapy doses based on the grade of leukopenia after a first standard dose.Patients and methods: 1452 women in Sweden and Denmark with operable node-positive or high-risk node-negative breast cancer aged 18-60 years were recruited to participate in this trial. Participants received a first FEC cycle at standard doses (600/60/600 mg/m2). Patients (n = 1052) with nadir leukopenia grade 0-2 after the first cycle were randomized between either 6 standard FEC or 6 tailored FEC courses with doses of epirubicin and cyclophosphamide escalated during courses 2 and 3 and thereafter aimed at achieving grade 3 leukopenia. Patients with nadir leukopenia grade 3-4 after the first course continued treatment with standard FEC. Results of the randomized comparison has been published previously. The present study focuses on chemotherapy-induced leukopenia as a covariable with outcome in randomized and non-randomized patients. The prognostic value of leukopenia after course 3, was studied in a Cox model adjusted for cumulative doses of epirubicin and cyclophosphamide. The association of chemotherapy-induced leukopenia with prognosis was a preplanned secondary endpoint for this trial.Results: The eight-year distant disease-free survival was 73%, 77%, 78% and 83% for patients with leucocyte nadir grade 0, 1, 2 and 3-4, respectively. Higher degree of leukopenia was highly significantly associated to improved distant disease-free survival (HR 0.84, 95% CI 0.74-0.96, p = .008) and overall survival (HR 0.87 (0.76-0.99, p = .032).Conclusion: This prospective study confirms that chemotherapy-induced leukopenia is a covariable with outcome in primary breast cancer, even after adjustment for chemotherapy doses.
    • Do negative intrusive thoughts at diagnosis predict impaired quality of life, depressed mood and waking up with anxiety 3, 12 and 24 months after radical prostatectomy? - a longitudinal study.

      Bock, David; Angenete, Eva; Asplund, Dan; Bjartell, Anders; Carlsson, Stefan; Hugosson, Jonas; Stinesen Kollberg, Karin; Lantz, Anna; Nilsson, Hanna; Prytz, Mattias; et al. (Taylor & Francis, 2020-04-28)
      Objective: To evaluate the effect of intrusive thoughts at diagnosis on quality of life, depressed mood and waking up with anxiety up to two years after radical prostatectomy.Method: The Laparoscopic Prostatectomy Robot Open (LAPPRO) trial was a prospective, longitudinal multicenter study of 4003 patients undergoing radical prostatectomy. Questionnaire data were collected preoperatively, at 3, 12 and 24 months after surgery.Results: The group of patients with intrusive thoughts at diagnosis had a statistically significant higher postoperative prevalence of impaired quality of life, depressed mood and waking up with anxiety as compared with the group of patients with no or minor intrusive thoughts. The highest risk increase for impaired QoL, depressed mood and waking up with anxiety ≥1/week was at 12, 3 and 3 months, respectively, where the three outcomes increased by 38% (RR: 1.38; 95%CI: 1.27-1.49)), 136% (RR: 2.36; 95%CI: 1.74-3.19)) and 165% (RR: 2.65; 95%CI: 2.22-3.17)), respectively.Conclusions: The demonstrated link between intrusive thoughts and quality of life, depressed mood and waking up with anxiety deliver is further evidence to the idea that intrusive thoughts has potential as an endpoint for assessing and predicting psychological distress among men with prostate cancer diagnosis.Trial registration number: ISRCTN06393679 (www.isrctn.com). Date of registration: 07/02/2008. Retrospectively registered.
    • Changes in the left temporal microstate are a sign of cognitive decline in patients with Alzheimer's disease.

      Musaeus, Christian S; Engedal, Knut; Høgh, Peter; Jelic, Vesna; Khanna, Arjun R; Kjaer, Troels Wesenberg; Mørup, Morten; Naik, Mala; Oeksengaard, Anne-Rita; Santarnecchi, Emiliano; et al. (Wiley, 2020-04-27)
      Introduction: Large-scale brain networks are disrupted in the early stages of Alzheimer's disease (AD). Electroencephalography microstate analysis, a promising method for studying brain networks, parses EEG signals into topographies representing discrete, sequential network activations. Prior studies indicate that patients with AD show a pattern of global microstate disorganization. We investigated whether any specific microstate changes could be found in patients with AD and mild cognitive impairment (MCI) compared to healthy controls (HC). Materials and methods: Standard EEGs were obtained from 135 HC, 117 patients with MCI, and 117 patients with AD from six Nordic memory clinics. We parsed the data into four archetypal microstates. Results: There was significantly increased duration, occurrence, and coverage of microstate A in patients with AD and MCI compared to HC. When looking at microstates in specific frequency bands, we found that microstate A was affected in delta (1-4 Hz), theta (4-8 Hz), and beta (13-30 Hz), while microstate D was affected only in the delta and theta bands. Microstate features were able to separate HC from AD with an accuracy of 69.8% and HC from MCI with an accuracy of 58.7%. Conclusions: Further studies are needed to evaluate whether microstates represent a valuable disease classifier. Overall, patients with AD and MCI, as compared to HC, show specific microstate alterations, which are limited to specific frequency bands. These alterations suggest disruption of large-scale cortical networks in AD and MCI, which may be limited to specific frequency bands.
    • Radiographic scoring systems for psoriatic arthritis are insufficient for psoriatic arthritis mutilans: results from the Nordic PAM Study.

      Laasonen, Leena; Lindqvist, Ulla; Iversen, Lars; Ejstrup, Leif; Jonmundsson, Thorarinn; Ståhle, Mona; Gudbjornsson, Bjorn; 1Helsinki Medical Imaging Center, Helsinki University Central Hospital, Helsinki, Finland. 2Department of Medical Sciences, Rheumatology, Uppsala University, Uppsala, Sweden. 3Department of Dermatology, Aarhus University Hospital, Aarhus, Denmark. 4Department of Rheumatology, Odense University Hospital, Odense, Denmark. 5Centre for Rheumatology Research, University Hospital and Faculty of Medicine, University of Iceland, Reykjavik, Iceland. 6Dermatology Division, Department of Medicine, Karolinska Institutet, Stockholm, Sweden. (SAGE Publications, 2020-04-27)
      Background: Psoriatic arthritis mutilans (PAM) is the most severe phenotype of psoriatic arthritis (PsA). Purpose: To describe the radiological features in PAM and explore whether existing scoring systems for radiological damage in psoriatic arthritis are applicable for PAM. Material and methods: Radiographs were scored according to the modified Sharp-van der Heijde (mSvdH) and the Psoriatic Arthritis Ratingen Score (PARS) systems for PsA. Results: At inclusion, 55 PAM patients (49% women, mean age 58 ± 12 years) had conventional radiographs of both hands and feet. A total of 869 PAM joints were detected and 193 joints with ankylosis. The mean total mSvdH score was 213.7 ± 137.8 (41% of maximum) with a higher score for hands than for feet: 136.6 ± 90.1 vs. 79.1 ± 60.9. However, the total score was relatively higher in the feet than in the hands when compared to the highest possible scoring (47% vs. 38% of max). The mean total PARS score was 126.3 ± 79.6 (35% of max). Scoring for joint destruction was higher than for proliferation (22% vs. 11% of max). Strong correlation was found between mSvdH and PARS (r2 = 0.913). A significant correlation was found between scoring and duration of arthritis and the Health Assessment Questionnaire. History of smoking, BMI, and gender did not influence the scoring values. Conclusions: The two scoring systems studied may not be ideal to indicate progression of PAM in advanced disease since they reach ceiling effects rather early. Therefore, reporting early signs suggestive of PAM, e.g. signs of pencil-in-cup deformities or osteolysis, is crucial. This would reveal the presence of PAM and might lead to improved treatment in order to minimize joint damage. Keywords: Psoriatic arthritis; mutilans; psoriasis; radiology; scoring systems.
    • Predicted loss and gain of function mutations in ACO1 are associated with erythropoiesis.

      Oskarsson, Gudjon R; Oddsson, Asmundur; Magnusson, Magnus K; Kristjansson, Ragnar P; Halldorsson, Gisli H; Ferkingstad, Egil; Zink, Florian; Helgadottir, Anna; Ivarsdottir, Erna V; Arnadottir, Gudny A; et al. (Nature Publishing Group, 2020-04-23)
      Hemoglobin is the essential oxygen-carrying molecule in humans and is regulated by cellular iron and oxygen sensing mechanisms. To search for novel variants associated with hemoglobin concentration, we performed genome-wide association studies of hemoglobin concentration using a combined set of 684,122 individuals from Iceland and the UK. Notably, we found seven novel variants, six rare coding and one common, at the ACO1 locus associating with either decreased or increased hemoglobin concentration. Of these variants, the missense Cys506Ser and the stop-gained Lys334Ter mutations are specific to eight and ten generation pedigrees, respectively, and have the two largest effects in the study (EffectCys506Ser = -1.61 SD, CI95 = [-1.98, -1.35]; EffectLys334Ter = 0.63 SD, CI95 = [0.36, 0.91]). We also find Cys506Ser to associate with increased risk of persistent anemia (OR = 17.1, P = 2 × 10-14). The strong bidirectional effects seen in this study implicate ACO1, a known iron sensing molecule, as a major homeostatic regulator of hemoglobin concentration.
    • Women and intimate partner violence: Prevalence of hospital visits and nature of injuries in the Icelandic population.

      Jónasdóttir, Drífa; Thorsteinsdottir, Thordis; Ásgeirsdóttir, Tinna Laufey; Lund, Sigrún H; Arnarsson, Eiríkur Örn; Ashikali, Eleni; Líndal, Þórhildur; Mogensen, Brynjólfur; 1Faculty of Medicine, University of Iceland, Reykjavik, Iceland. 2Research Institute in Emergency Medicine, Reykjavik, Iceland. 3Faculty of Nursing, University of Iceland, Reykjavik, Iceland. 4Faculty of Economics, University of Iceland, Reykjavik, Iceland. 5The Centre of Public Health Sciences, University of Iceland, Reykjavik, Iceland. 6Department of Psychiatry, Landspitali National University Hospital, Reykjavik, Iceland. 7Formerly at School of Psychology, University of Sussex, Brighton, UK. 8The Ombudsman for Children in Iceland, Reykjavik, Iceland. 9Emergency Department, Landspitali National University Hospital, Reykjavik, Iceland. (SAGE Publications, 2020-04-20)
      Aims: The purpose of this study was to analyse the prevalence of hospital visits and nature of injuries caused by intimate partner violence (IPV) against women and associated costs. Methods: All visits to Landspitali National University Hospital by women 18 years or older subjected to IPV, inflicted by a current or former male partner during 2005-2014, were observed and analysed. Information was obtained on number, date and time of visits and admissions, place of occurrence, patients' and perpetrators' age and relationship, number of perpetrators, medical diagnosis, aetiology, injury severity and cost. Results: The number of new hospital visits due to IPV was 1454, of which 92.6% were to the Emergency Department. The average age of the women was 34 years and 3.2% were admitted. According to the Injury Severity Score, physical injuries were mostly minor (92.4%) and mainly located on the upper body (64.3%) - namely, face, head and neck (37.1%) and upper limbs (27.2%). The majority of injuries were superficial (76.2%) and punching (29.7%), shoving (17.8%), kicking (10.5%) and attempted strangulation (9.8%) were the most common types of aetiology. Repeated new visits were 37.8%. The total cost for the hospital relating to IPV was €783,330. Conclusions: The total number of new visits resulting from IPV was 1454, and prevalence was 1.69 per 1000 women in the capital area over the research period. The majority of women were shown to have minor physical injuries of a superficial nature, located on the upper body. Although a low percentage of women were admitted, the associated cost for visits and admissions was substantial.
    • Effects of amotosalen treatment on human platelet lysate bioactivity: A proof-of-concept study.

      Christensen, Christian; Jonsdottir-Buch, Sandra Mjoll; Sigurjonsson, Olafur Eysteinn; 1The Blood Bank, The National University Hospital of Iceland, Reykjavik, Iceland. 2Faculty of Medicine, Biomedical Center, University of Iceland, Reykjavik, Iceland. 3Platome Biotechnology, Hafnarfjörður, Iceland. 4School of Science and Engineering, University of Reykjavik, Reykjavik, Iceland. (Public Library of Science, 2020-04-15)
      Background: Clinical application of mesenchymal stromal cells (MSCs) usually requires an in vitro expansion step to reach clinically relevant numbers. In vitro cell expansion necessitates supplementation of basal mammalian cell culture medium with growth factors. To avoid using supplements containing animal substances, human platelet lysates (hPL) produced from expired and pathogen inactivated platelet concentrates can be used in place of fetal bovine serum. However, globally, most transfusion units are currently not pathogen inactivated. As blood banks are the sole source of platelet concentrates for hPL production, it is important to ensure product safety and standardized production methods. In this proof-of-concept study we assessed the feasibility of producing hPL from expired platelet concentrates with pathogen inactivation applied after platelet lysis by evaluating the retention of growth factors, cytokines, and the ability to support MSC proliferation and tri-lineage differentiation. Methodology/principal findings: Bone marrow-derived MSCs (BM-MSCs) were expanded and differentiated using hPL derived from pathogen inactivated platelet lysates (hPL-PIPL), with pathogen inactivation by amotosalen/ultraviolet A treatment applied after lysis of expired platelets. Results were compared to those using hPL produced from conventional expired pathogen inactivated platelet concentrates (hPL-PIPC), with pathogen inactivation applied after blood donation. hPL-PIPL treatment had lower concentrations of soluble growth factors and cytokines than hPL-PIPC treatment. When used as supplementation in cell culture, BM-MSCs proliferated at a reduced rate, but more consistently, in hPL-PIPL than in hPL-PIPC. The ability to support tri-lineage differentiation was comparable between lysates. Conclusion/significance: These results suggest that functional hPL can be produced from expired and untreated platelet lysates by applying pathogen inactivation after platelet lysis. When carried out post-expiration, pathogen inactivation may provide a valuable solution for further standardizing global hPL production methods, increasing the pool of starting material, and meeting future demand for animal-free supplements in human cell culturing.
    • Increase in the incidence of alcoholic pancreatitis and alcoholic liver disease in Iceland: impact of alcohol consumption.

      Hauksson, Kristjan; Arnardottir, Margret; Agustsson, Arnar S; Magnusdottir, Berglind A; Baldursdottir, Maria B; Lund, Sigrun H; Kalaitzakis, Evangelos; Björnsson, Einar S; 1Department of Gastroenterology, Landspitali University Hospital, Reykjavik, Iceland. 2Faculty of Medicine, University of Iceland, Reykjavik, Iceland. 3Decode Genetics, Reykjavik, Iceland, Copenhagen, Denmark. 4Digestive Disease Center, Copenhagen University Hospital/Herlev, University of Copenhagen, Copenhagen, Denmark. (Taylor & Francis, 2020-04-14)
      Objective: To analyze the incidence of acute alcoholic pancreatitis and of severe alcoholic liver disease (ALD) and its association with per capita alcohol consumption with identification of both alcoholic cirrhosis (AC) and severe alcoholic hepatitis (AH), in a population-based setting.Methods: A search was undertaken in diagnoses database for diagnostic codes in order to find patients hospitalized with incident acute alcoholic pancreatitis (AP) and alcoholic liver disease in Iceland in 2001-2015. Diagnoses were verified in all patients who were retrospectively reviewed. Those with ALD had either AC or AH. Alcohol sales during the study period were obtained from Statistics Iceland.Results: Overall, 273 patients with acute AP, mean age at diagnosis 50 (14) years, 74% males and 159 patients with ALD, mean age 57 (11) years, 73% males, were identified. Mean per capita alcohol consumption was 6.95 (0.4) liters and increased by 21% over the study period. The annual incidence of AP increased from 4.2 per 100.000 to 9.5 and ALD from 1.6 to 6.1 per 100.000. Trend analysis showed a significant annual increase of 7% (RR 1.07, 95%CI 1.04-1.10) for AP and an annual increase of 10.5% (RR 1.10, 95%CI 1.06-1.15) for ALD. The increase was only significant in males.Conclusions: Increase per capita alcohol consumption over a 15 year study period was associated with an increase in the incidence of severe alcoholic liver disease and alcohol-related acute pancreatitis in males but not in females.
    • Risk of hernia formation after radical prostatectomy: a comparison between open and robot-assisted laparoscopic radical prostatectomy within the prospectively controlled LAPPRO trial.

      Nilsson, H; Stranne, J; Hugosson, J; Wessman, C; Steineck, G; Bjartell, A; Carlsson, S; Thorsteinsdottir, T; Tyritzis, S I; Lantz, A; et al. (Springer, 2020-04-11)
      Purpose: In addition to incisional hernia, inguinal hernia is a recognized complication to radical retropubic prostatectomy. To compare the risk of developing inguinal and incisional hernias after open radical prostatectomy compared to robot-assisted laparoscopic prostatectomy. Method: Patients planned for prostatectomy were enrolled in the prospective, controlled LAPPRO trial between September 2008 and November 2011 at 14 hospitals in Sweden. Information regarding patient characteristics, operative techniques and occurrence of postoperative inguinal and incisional hernia were retrieved using six clinical record forms and four validated questionnaires. Results: 3447 patients operated with radical prostatectomy were analyzed. Within 24 months, 262 patients developed an inguinal hernia, 189 (7.3%) after robot-assisted laparoscopic prostatectomy and 73 (8.4%) after open radical prostatectomy. The relative risk of having an inguinal hernia after robot-assisted laparoscopic prostatectomy was 18% lower compared to open radical retropubic prostatectomy, a non-significant difference. Risk factors for developing an inguinal hernia after prostatectomy were increased age, low BMI and previous hernia repair. The incidence of incisional hernia was low regardless of surgical technique. Limitations are the non-randomised setting. Conclusions: We found no difference in incidence of inguinal hernia after open retropubic and robot-assisted laparoscopic radical prostatectomy. The low incidence of incisional hernia after both procedures did not allow for statistical analysis. Risk factors for developing an inguinal hernia after prostatectomy were increased age and BMI.
    • Use of serotonin reuptake inhibitors is not associated with increased bleeding after CABG.

      Heimisdottir, Alexandra A; Enger, Eric; Morelli, Simon; Johannesdottir, Hera; Helgadottir, Solveig; Sigurðsson, Engilbert; Gudbjartsson, Tomas; 1Department of Cardiothoracic Surgery, Landspitali University Hospital, Reykjavik, Iceland. 2Faculty of Medicine, University of Iceland, Reykjavik, Iceland. 3Department of Medicine and Health, Linköping University, Linköping, Sweden. 4Anesthesiology and Intensive Care, Akademiska University Hospital, Uppsala, Sweden. 5Department of Psychiatry, Landspitali University Hospital, Reykjavik, Iceland. 6Department of Cardiothoracic Surgery, Landspitali University Hospital, Reykjavik, Iceland. tomasgud@landspitali.is. 7Faculty of Medicine, University of Iceland, Reykjavik, Iceland. tomasgud@landspitali.is. (Springer, 2020-04-11)
      Objectives: Selective serotonin reuptake inhibitors (SSRIs) and serotonin noradrenaline reuptake inhibitors (SNRIs) are the most commonly prescribed antidepressants worldwide. Studies suggest that SSRI/SNRIs can increase bleeding following different surgical procedures, including open heart surgery, but results are conflicting. The objective of this study was to analyse their effects on bleeding after coronary artery bypass grafting (CABG). Methods: Of 1237 patients that underwent CABG in Iceland in 2007-2016, 97 (7.8%) used SSRIs/SNRIs preoperatively and were compared to a reference group (n = 1140). Bleeding was assessed using 24-h chest-tube output, number of RBC units transfused and reoperation for bleeding. Thirty-day mortality rates and incidence of complications were also compared. Results: The two groups were comparable with respect to preoperative and operative variables, with the exception of BMI being significantly higher in the SSRI/SNRI group (30.2 vs. 28.3 kg/m2, p < 0.001). No significant differences were observed between groups in 24-h chest-tube output [815 (SSRI/SNRI) vs. 877 ml (reference), p = 0.26], number of RBC units transfused (2.2 vs. 2.2, p = 0.99) or the rate of reoperation for bleeding (4.1% vs. 6.0%, p = 0.61). The incidences of complications and 30-day mortality rate were also similar. Conclusions: Using three different criteria, preoperative use of SSRIs/SNRIs was not shown to increase bleeding after CABG. Furthermore, short-term complications as well as 30-day mortality rates did not differ from those of controls. Thus, temporary cessation of SSRI/SNRI treatment prior to CABG to decrease the risk of bleeding is unwarranted.
    • Femoral nerve blocks for the treatment of acute pre-hospital pain: A systematic review with meta-analysis.

      Raatiniemi, Lasse; Magnusson, Vidar; Hyldmo, Per K; Friesgaard, Kristian D; Kongstad, Poul; Kurola, Jouni; Larsen, Robert; Rehn, Marius; Rognås, Leif; Sandberg, Mårten; et al. (Wiley, 2020-04-09)
      Background: Pain management is one of the most important interventions in the emergency medical services. The femoral nerve block (FNB) is, among other things, indicated for pre- and post-operative pain management for patients with femoral fractures but its role in the pre-hospital setting has not been determined. The aim of this review was to assess the effect and safety of the FNB in comparison to other forms of analgesia (or no treatment) for managing acute lower extremity pain in adult patients in the pre-hospital setting. Methods: A systematic review (PROSPERO registration (CRD42018114399)) was conducted. The Cochrane and GRADE methods were used to assess outcomes. Two authors independently reviewed each study for eligibility, extracted the data and performed risk of bias assessments. Results: Four studies with a total of 252 patients were included. Two RCTs (114 patients) showed that FNB may reduce pain more effectively than metamizole (mean difference 32 mm on a 100 mm VAS (95% CI 24 to 40)). One RCT (48 patients) compared the FNB with lidocaine and magnesium sulphate to FNB with lidocaine alone and was only included here for information regarding adverse effects. One case series included 90 patients. Few adverse events were reported in the included studies. The certainty of evidence was very low. We found no studies comparing FNB to inhaled analgesics, opioids or ketamine. Conclusions: Evidence regarding the effectiveness and adverse effects of pre-hospital FNB is limited. Studies comparing pre-hospital FNB to inhaled analgesics, opioids or ketamine are lacking.
    • Severe desaturations increase psychomotor vigilance task-based median reaction time and number of lapses in obstructive sleep apnoea patients.

      Kainulainen, Samu; Duce, Brett; Korkalainen, Henri; Oksenberg, Arie; Leino, Akseli; Arnardottir, Erna S; Kulkas, Antti; Myllymaa, Sami; Töyräs, Juha; Leppänen, Timo; et al. (European Respiratory Society, 2020-04-09)
      Current diagnostic parameters estimating obstructive sleep apnoea (OSA) severity have a poor connection to the psychomotor vigilance of OSA patients. Thus, we aimed to investigate how the severity of apnoeas, hypopnoeas and intermittent hypoxaemia is associated with impaired vigilance.We retrospectively examined type I polysomnography data and corresponding psychomotor vigilance tasks (PVTs) of 743 consecutive OSA patients (apnoea-hypopnoea index (AHI) ≥5 events·h-1). Conventional diagnostic parameters (e.g. AHI and oxygen desaturation index (ODI)) and novel parameters (e.g. desaturation severity and obstruction severity) incorporating duration of apnoeas and hypopnoeas as well as depth and duration of desaturations were assessed. Patients were grouped into quartiles based on PVT outcome variables. The odds of belonging to the worst-performing quartile were assessed. Analyses were performed for all PVT outcome variables using binomial logistic regression.A relative 10% increase in median depth of desaturations elevated the odds (ORrange 1.20-1.37, p<0.05) of prolonged mean and median reaction times as well as increased lapse count. Similarly, an increase in desaturation severity (ORrange 1.26-1.52, p<0.05) associated with prolonged median reaction time. Female sex (ORrange 2.21-6.02, p<0.01), Epworth Sleepiness Scale score (ORrange 1.05-1.07, p<0.01) and older age (ORrange 1.01-1.05, p<0.05) were significant risk factors in all analyses. In contrast, increases in conventional AHI, ODI and arousal index were not associated with deteriorated PVT performance.These results show that our novel parameters describing the severity of intermittent hypoxaemia are significantly associated with increased risk of impaired PVT performance, whereas conventional OSA severity and sleep fragmentation metrics are not. These results underline the importance of developing the assessment of OSA severity beyond the AHI.
    • Hypertrophic cardiomyopathy in myosin-binding protein C (MYBPC3) Icelandic founder mutation carriers.

      Adalsteinsdottir, Berglind; Burke, Michael; Maron, Barry J; Danielsen, Ragnar; Lopez, Begoña; Diez, Javier; Jarolim, Petr; Seidman, Jonathan; Seidman, Christine E; Ho, Carolyn Y; et al. (BMJ Publishing Group, 2020-04-05)
      Objective: The myosin-binding protein C (MYBPC3) c.927-2A>G founder mutation accounts for >90% of sarcomeric hypertrophic cardiomyopathy (HCM) in Iceland. This cross-sectional observational study explored the penetrance and phenotypic burden among carriers of this single, prevalent founder mutation. Methods: We studied 60 probands with HCM caused by MYBPC3 c.927-2A>G and 225 first-degree relatives. All participants underwent comprehensive clinical evaluation and relatives were genotyped. Results: Genetic and clinical evaluation of relatives identified 49 genotype-positive (G+) relatives with left ventricular hypertrophy (G+/LVH+), 59 G+without LVH (G+/LVH-) and 117 genotype-negative relatives (unaffected). Compared with HCM probands, G+/LVH+ relatives were older at HCM diagnosis, had less LVH, a less prevalent diastolic dysfunction, fewer ECG abnormalities, lower serum N-terminal pro-B-type natriuretic peptide (NT-proBNP) and high-sensitivity cardiac troponin I levels, and fewer symptoms. The penetrance of HCM was influenced by age and sex; specifically, LVH was present in 39% of G+males but only 9% of G+females under age 40 years (p=0.015), versus 86% and 83%, respectively, after age 60 (p=0.89). G+/LVH- subjects had normal wall thicknesses, diastolic function and NT-proBNP levels, but subtle changes in LV geometry and more ECG abnormalities than their unaffected relatives. Conclusions: Phenotypic expression of the Icelandic MYBPC3 founder mutation varies by age, sex and proband status. Men are more likely to have LVH at a younger age, and disease manifestations were more prominent in probands than in relatives identified via family screening. G+/LVH- individuals had subtle clinical differences from unaffected relatives well into adulthood, indicating subclinical phenotypic expression of the pathogenic mutation.
    • Lifestyle and 25-hydroxy-vitamin D among community-dwelling old adults with dementia, mild cognitive impairment, or normal cognitive function.

      Eymundsdottir, Hrafnhildur; Chang, M; Geirsdottir, O G; Gudmundsson, L S; Jonsson, P V; Gudnason, V; Launer, L; Jonsdottir, M K; Ramel, A; 1Faculty of Food Science and Nutrition, University of Iceland, Reykjavík, Iceland. hre6@hi.is. 2The Icelandic Gerontological Research Center, The National University Hospital of Iceland, Tungata 26, 101, Reykjavík, Iceland. hre6@hi.is. 3The Icelandic Gerontological Research Center, The National University Hospital of Iceland, Tungata 26, 101, Reykjavík, Iceland. 4Faculty of Health Promotion, Sport and Leisure Studies, School of Education, University of Iceland, Reykjavík, Iceland. 5Faculty of Food Science and Nutrition, University of Iceland, Reykjavík, Iceland. 6Faculty of Pharmaceutical Sciences, School of Health Sciences, University of Iceland, Reykjavík, Iceland. 7Faculty of Medicine, University of Iceland, Reykjavík, Iceland. 8Department of Geriatrics, The National University Hospital of Iceland, Reykjavík, Iceland. 9Icelandic Heart Association, Kópavogur, Iceland. 10Laboratory of Epidemiology and Population Sciences, National Institute On Aging, National Institutes of Health (NIH), Bethesda, MD, USA. 11Department of Psychology, Reykjavik University, Reykjavík, Iceland. 12Mental Health Services (Memory Clinic) Landspitali-The National University Hospital of Iceland, Reykjavík, Iceland. (Springer, 2020-04-04)
      ackground: Several studies have indicated that older adults with cognitive impairment have a poorer lifestyle than their healthy peers including lower 25-hydroxy-vitamin D levels (25OHD). Aim: To investigate the associations between lifestyle and 25OHD depending on cognitive status among old adults. Methods: Community-dwelling old adults (65-96 years) participated in this cross-sectional study based on the Age-Gene/Environment-Susceptibility-Reykjavik-Study. The analytical sample included 5162 subjects who were stratified by cognitive status, i.e., dementia (n = 307), mild cognitive impairment (MCI, n = 492), and normal cognitive status (NCS, n = 4363). Lifestyle variables were assessed and 25OHD was measured. The associations between lifestyle and 25OHD were calculated using linear models correcting for potential confounders. Results: According to linear regression models, 25OHD was significantly lower in older people with dementia (53.8 ± 19.6 nmol/L) than in NCS participants (57.6 ± 17.7 nmol/L). Cod liver oil (7.1-9.2 nmol/L, P < 0.001) and dietary supplements (4.4-11.5 nmol/L, P < 0.001) were associated with higher 25OHD in all three groups. However, physical activity ≥ 3 h/week (2.82 nmol/L, P < 0.001), BMI < 30 kg/m2 (5.2 nmol/L, P < 0.001), non-smoking (4.8 nmol/L, P < 0.001), alcohol consumption (2.7 nmol/L, P < 0.001), and fatty fish consumption ≥ 3x/week (2.6 nmol/L, P < 0.001) were related to higher 25OHD in NCS only, but not in participants with dementia or MCI. Discussion: Older people living in Iceland with dementia are at higher risk for 25OHD deficiency when compared to healthy individuals. Physical activity reported among participants with dementia, and MCI is low and is not significantly associated with 25OHD. Conclusions: Lifestyle factors among NCS participants are associated with 25OHD levels. Importantly, healthy lifestyle should be promoted among individuals with MCI and dementia.
    • Visualizing metabolic network dynamics through time-series metabolomic data.

      Buchweitz, Lea F; Yurkovich, James T; Blessing, Christoph; Kohler, Veronika; Schwarzkopf, Fabian; King, Zachary A; Yang, Laurence; Jóhannsson, Freyr; Sigurjónsson, Ólafur E; Rolfsson, Óttar; et al. (BioMed Central, 2020-04-03)
      Background: New technologies have given rise to an abundance of -omics data, particularly metabolomic data. The scale of these data introduces new challenges for the interpretation and extraction of knowledge, requiring the development of innovative computational visualization methodologies. Here, we present GEM-Vis, an original method for the visualization of time-course metabolomic data within the context of metabolic network maps. We demonstrate the utility of the GEM-Vis method by examining previously published data for two cellular systems-the human platelet and erythrocyte under cold storage for use in transfusion medicine. Results: The results comprise two animated videos that allow for new insights into the metabolic state of both cell types. In the case study of the platelet metabolome during storage, the new visualization technique elucidates a nicotinamide accumulation that mirrors that of hypoxanthine and might, therefore, reflect similar pathway usage. This visual analysis provides a possible explanation for why the salvage reactions in purine metabolism exhibit lower activity during the first few days of the storage period. The second case study displays drastic changes in specific erythrocyte metabolite pools at different times during storage at different temperatures. Conclusions: The new visualization technique GEM-Vis introduced in this article constitutes a well-suitable approach for large-scale network exploration and advances hypothesis generation. This method can be applied to any system with data and a metabolic map to promote visualization and understand physiology at the network level. More broadly, we hope that our approach will provide the blueprints for new visualizations of other longitudinal -omics data types. The supplement includes a comprehensive user's guide and links to a series of tutorial videos that explain how to prepare model and data files, and how to use the software SBMLsimulator in combination with further tools to create similar animations as highlighted in the case studies.
    • The better sleep better well-being programme: Educating and training community healthcare nurses in developing interventions for families of infants with moderate sleep problems: a pilot study.

      Skuladottir, Arna; Sigurdardottir, Anna Olafia; Svavarsdottir, Erla Kolbrun; 1Landspitali University Hospital, Reykjavik, Iceland. 2Faculty of Nursing, University of Iceland and Landspitali University Hospital, Reykjavik, Iceland. 3Faculty of University of Iceland and Landspitali University Hospital, Reykjavik, Iceland. (Wiley, 2020-04-02)
      he main aim of this pilot study was to evaluate the benefit of the Better Sleep Better Well-being (BSBW) educational and training intervention programme regarding infants sleep problems for Community Health Care (CHC) nurses, on their perceptions on their family nursing practice skills and on their job demand, control and support. There were 6 CHC nurses who participated in the BSBW programme, and 26 nurses in the comparison group. The programme consisted of 4 sessions (8 hours per session) of lectures on the aetiology of infants sleep problems as well as on evidence-based and family relational practices and on 20 sessions of clinical cases, scenarios, discussions and reflections. The main finding indicated that the nurses in the intervention group reported significantly higher family nursing practices skills compared to the nurses in the comparison group. The findings are promising, since they offered additional resources to the CHC nurses, in their clinical practices.