Landspítali University Hospital Research Archive
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Postoperative Acute Kidney Injury Is Associated With Progression of Chronic Kidney Disease Independent of Severity.
No full textTo access publisher's full text version of this article click on the hyperlink belowBackground: Both postoperative acute kidney injury (AKI) and preoperative chronic kidney disease (CKD) are associated with significantly worse outcomes following surgery. The relationship of both of these conditions with each other and with CKD progression after surgery remains poorly studied. Our objective was to assess if there was an interaction between preoperative kidney function estimated by preoperative estimated glomerular filtration rate (eGFR)/CKD stage, postoperative AKI, and eGFR/CKD progression within 1 year of surgery. Our hypothesis was that AKI severity would be associated with a faster time to eGFR/CKD stage progression within 1 year of surgery in a graded-fashion, which would be exacerbated by preoperative kidney dysfunction.
Methods: This was a retrospective cohort study at Landspitali University Hospital in Iceland, which serves about 75% of the population. Participants included adults receiving their first major anesthetic between 2005 and 2018. Patients with CKD stage 5, undergoing major urologic procedures, or having missing creatinine values for follow-up of eGFR stage were excluded from analysis. The primary exposure was postoperative AKI stage within 7 days after surgery classified by the kidney disease improving global outcome (KDIGO) criteria. The primary outcome was time to progression of CKD by at least 1 eGFR/CKD stage within 1-year following surgery. Multivariable Cox proportional hazards models were used to estimate hazard of eGFR/CKD stage progression, including an interaction between AKI and preoperative CKD on eGFR/CKD stage progression.
Results: A total of 5548 patients were studied. In the multivariable model adjusting for baseline eGFR/CKD stage, when compared to patients without AKI, postoperative AKI stage 1 (hazard ratio [HR], 5.91; 95% confidence interval [CI], 4.34-8.05), stage 2 (HR, 3.86; 95% CI, 1.82-8.16), and stage 3 (HR, 3.61; 95% CI, 1.49-8.74) were all independently associated with faster time to eGFR/CKD stage progression within 1 year following surgery, though increasing AKI severity did not confer additional risk. The only significant interaction between the degree of AKI and the preexisting renal function was for stage 1 AKI, where the odds of 1-year eGFR/CKD stage progression actually decreased in patients with preoperative CKD categories 3a, 3b, and 4.
Conclusions: KDIGO-AKI was independently associated with eGFR/CKD stage progression within the year following surgery after adjustment for baseline eGFR/CKD stage and without an interaction between worse preoperative kidney function and higher stage AKI. Our observations suggest that further studies are warranted to test whether CKD progression could be prevented by the adoption of perioperative kidney protective practices
X-linked serotonin 2C receptor is associated with a non-canonical pathway for sudden unexpected death in epilepsy.
Full text linkTo 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 DownloadSudden Unexpected Death in Epilepsy is a leading cause of epilepsy-related mortality, and the analysis of mouse Sudden Unexpected Death in Epilepsy models is steadily revealing a spectrum of inherited risk phenotypes based on distinct genetic mechanisms. Serotonin (5-HT) signalling enhances post-ictal cardiorespiratory drive and, when elevated in the brain, reduces death following evoked audiogenic brainstem seizures in inbred mouse models. However, no gene in this pathway has yet been linked to a spontaneous epilepsy phenotype, the defining criterion of Sudden Unexpected Death in Epilepsy. Most monogenic models of Sudden Unexpected Death in Epilepsy invoke a failure of inhibitory synaptic drive as a critical pathogenic step. Accordingly, the G protein-coupled, membrane serotonin receptor 5-HT2C inhibits forebrain and brainstem networks by exciting GABAergic interneurons, and deletion of this gene lowers the threshold for lethal evoked audiogenic seizures. Here, we characterize epileptogenesis throughout the lifespan of mice lacking X-linked, 5-HT2C receptors (loxTB Htr2c). We find that loss of Htr2c generates a complex, adult-onset spontaneous epileptic phenotype with a novel progressive hyperexcitability pattern of absences, non-convulsive, and convulsive behavioural seizures culminating in late onset sudden mortality predominantly in male mice. RNAscope localized Htr2c mRNA in subsets of Gad2+ GABAergic neurons in forebrain and brainstem regions. To evaluate the contribution of 5-HT2C receptor-mediated inhibitory drive, we selectively spared their deletion in GAD2+ GABAergic neurons of pan-deleted loxTB Htr2c mice, yet unexpectedly found no amelioration of survival or epileptic phenotype, indicating that expression of 5-HT2C receptors in GAD2+ inhibitory neurons was not sufficient to prevent hyperexcitability and lethal seizures. Analysis of human Sudden Unexpected Death in Epilepsy and epilepsy genetic databases identified an enrichment of HTR2C non-synonymous variants in Sudden Unexpected Death in Epilepsy cases. Interestingly, while early lethality is not reflected in the mouse model, we also identified variants mainly among male Sudden Infant Death Syndrome patients. Our findings validate HTR2C as a novel, sex-linked candidate gene modifying Sudden Unexpected Death in Epilepsy risk, and demonstrate that the complex epilepsy phenotype does not arise solely from 5-HT2C-mediated synaptic disinhibition. These results strengthen the evidence for the serotonin hypothesis of Sudden Unexpected Death in Epilepsy risk in humans, and advance current efforts to develop gene-guided interventions to mitigate premature mortality in epilepsy.United States Department of Health & Human Services
National Institutes of Health (NIH) - USA
NIH National Institute of Neurological Disorders & Stroke (NINDS)
Citizens United for Research in Epilepsy
Blue Bird Circle Foundation for Pediatric Researc
Impact of era of diagnosis on cause-specific late mortality among 77 423 five-year European survivors of childhood and adolescent cancer: The PanCareSurFup consortium.
No full textTo access publisher's full text version of this article click on the hyperlink belowLate mortality of European 5-year survivors of childhood or adolescent cancer has dropped over the last 60 years, but excess mortality persists. There is little information concerning secular trends in cause-specific mortality among older European survivors. PanCareSurFup pooled data from 12 cancer registries and clinics in 11 European countries from 77 423 five-year survivors of cancer diagnosed before age 21 between 1940 and 2008 followed for an average age of 21 years and a total of 1.27 million person-years to determine their risk of death using cumulative mortality, standardized mortality ratios (SMR), absolute excess risks (AER), and multivariable proportional hazards regression analyses. At the end of follow-up 9166 survivors (11.8%) had died compared to 927 expected (SMR 9.89, 95% confidence interval [95% CI] 9.69-10.09), AER 6.47 per 1000 person-years, (95% CI 6.32-6.62). At 60 to 68 years of attained age all-cause mortality was still higher than expected (SMR = 2.41, 95% CI 1.90-3.02). Overall cumulative mortality at 25 years from diagnosis dropped from 18.4% (95% CI 16.5-20.4) to 7.3% (95% CI 6.7-8.0) over the observation period. Compared to the diagnosis period 1960 to 1969, the mortality hazard ratio declined for first neoplasms (P for trend <.0001) and for infections (P < .0001); declines in relative mortality from second neoplasms and cardiovascular causes were less pronounced (P = .1105 and P = .0829, respectively). PanCareSurFup is the largest study with the longest follow-up of late mortality among European childhood and adolescent cancer 5-year survivors, and documents significant mortality declines among European survivors into modern eras. However, continuing excess mortality highlights survivors' long-term care needs.
Keywords: European; cardiovascular; causes of death; late mortality; second malignant neoplasms; survivors of childhood cancer.Barncancerfonden
Compagnia di San Paolo
Appeared in source as:Compagnia San Paolo; European Commission
Fondation Pfizer pour la Sante de L'enfant et de L'Adolescent
Fondo Chiara Rama ONLUS
French National Research Agency (ANR)
Institut National du Cancer (INCA) France
Appeared in source as:Institut National Du Cancer
Ministry of Health, Italy
Appeared in source as:Italian Ministry of Health Ricerca Corrente
Slovenian Research Agency - Slovenia
KWF Kankerbestrijding
Ligue nationale contre le cancer
Appeared in source as:La Ligue Nationale Contre le Cancer
Austrian Science Fund (FWF)
Swiss Cancer League
Swiss Cancer Research Foundation
Swiss Paediatric Oncology Group
Fondazione AIRC per la ricerca sul cancro
Appeared in source as:Italian Association for Cancer Researc
Causes of gastrointestinal bleeding in oral anticoagulant users compared to non-users in a population-based study.
No full textTo access publisher's full text version of this article click on the hyperlink belowBackground/aims: Causes of gastrointestinal bleeding (GIB) in patients on oral anticoagulants (OACs) are not well established. The aims of the study were to compare the causes of GIB in patients on OACs and those not on OAC therapy.
Methods: A nationwide study of all GIB events in patients on OACs in Iceland from 2014-2019 was conducted. Bleeding events were obtained through ICD-10 codes and review of endoscopy databases, confirmed by review of medical records. For comparison, patients not on OACs from previous Icelandic population-based studies were used.
Results: Among 752 GIB events in 12,005 patients on OACs, 273 (1.9%) had verified upper and 391 (2.7%) had verified lower GIB. For lower GIB, multivariate analysis showed that OAC users were more likely to have colonic polyps (OR 6.6, 95% CI: 2.4 - 17.8, p < .001) or colorectal cancer (OR 3.7, 95% CI: 2.0 - 7.0, p < .001) but less likely to have ischemic colitis (OR 0.11, 95% CI: 0.04 - 0.26, p < .001). For upper GIB, bleeding from mucosal erosions (OR 4.0 95% CI: 2.5 - 7.9, p < .001) and angiodysplasia (OR 3.6, 95%CI: 1.5 - 8.6, p = .003) were more common in OAC users.
Conclusions: A high proportion of GIB caused by colonic polyps and colorectal cancer among OAC patients indicates that OACs treatment may facilitate cancer diagnosis. The low proportion of ischemic colitis among those on OACs suggests that OACs provide a protective effect against ischemic colitis. OACs seem to increase the bleeding from angiodysplasia and mucosal erosive disease.
Keywords: Gastrointestinal bleeding; anticoagulation; colon cancer; ischemic colitis.Eimskipasjodur University of Iceland
Scientific grant of Landspital
Concussion among female athletes in Iceland: Stress, depression, anxiety, and quality of life
No full textTo access publisher's full text version of this article click on the hyperlink belowThe objective of the study was to examine the relationship between self-reported concussion history and stress, depression, anxiety, and quality of life among Icelandic female athletes. Participants were 508 Icelandic female athletes, aged 18–45 (M = 26.99, SD = 7.14), that had, or were currently training and competing in the two top leagues in basketball, soccer, and handball, in the top league in ice-hockey and national tournaments in mixed martial arts, taekwondo, karate, and boxing. Participants completed an online questionnaire regarding their age, sport, and concussion history before answering standard mental health scales concerning stress (PSS), depression (PHQ-9), anxiety (GAD-7), and quality of life (QOLS). Female athletes reporting a history of concussions scored higher on PSS, PHQ-9, and GAD-7 than those reporting no history of concussion. Scores on the QOLS were not significantly different between the groups. Female athletes that had sustained a concussion were 3.48 to 4.85 times more likely (depending on the number of concussions) to score above the clinical cut-off on PHQ-9 than those that had not sustained a concussion. Athletes that reported 2–3 or ≥ 4 concussions were 3.52 and 3.40 times more likely to score above the clinical cut-off on GAD-7, respectively. Results indicate that Icelandic female athletes with a history of concussion report more symptoms of distress than those with no history of concussion, and the higher number of concussions sustained, the worse they feel. © 2021 The Editors of Nordic Psychology
Resolution of Th/Tc17‐driven inflammation during anti‐TNFα treatment of rheumatoid arthritis reveals a unique immune biomarker profiling pattern
No full textTo access publisher's full text version of this article click on the hyperlink belowRheumatoid arthritis (RA) is a chronic multisystem disease with a complex immunopathology. Its inflammatory state is dominated by pro-inflammatory cytokines such as TNF alpha and activated Th1/Th17. Only proportion of patients achieve clinical remission despite potent biologics targeting these pathways. This study investigated the resolution of inflammation in RA patients (naive for biologics) receiving TNF alpha inhibitors (TNFi) and evaluated the biological mechanisms behind treatment response and assessed them using clinical scoring systems. The majority showed a good clinical response after six months (6M) and a significant drop in DAS28-CRP (P = 90%. Thus, the immunological complexity in RA is driven by a complex interplay of pro-inflammatory cytokines and effector T-cell response dominated by Th17/Tc17. In addition, the resolution of inflammation could be linked to a partially Treg-driven homeostatic innate immune response. Therefore, a more complex therapeutic approach against the above markers might be of value to obtain full clinical remission in the future.Celltrion Healthcar
Outpatient Use of Antimicrobials in Patients With Rheumatoid Arthritis Before and After Treatment With Tumor Necrosis Factor Inhibitors: A Nationwide Retrospective Cohort Study.
Full text linkTo 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 DownloadObjective: The objective of this study was to investigate the effect of tumor necrosis factor α inhibitor (TNFi) initiation on the use of antimicrobials among biologic-naïve patients with rheumatoid arthritis (RA).
Methods: Information on all biologic-naïve patients with RA was extracted from ICEBIO, a nationwide registry. Each patient was matched on age, sex, and calendar time to five randomly selected individuals from the general population. All filled antimicrobial and glucocorticoid prescriptions in the 2 years before and after initiation of the first TNFi were extracted from the Prescription Medicines Register. Prescriptions were quantified by using the number of filled prescriptions (NP) and defined daily doses.
Results: We extracted information on 359 patients with RA and 1795 comparators. During the 24 months before initiating treatment with TNFi, patients with RA received more prescriptions for antimicrobials than their matched general population comparators (mean ± SD: 2.8 ± 3.4 vs 1.6 ± 2.7; P < 0.001). The 24-month mean NP for patients with RA increased to 3.5 ± 3.9 (P < 0.001) after initiating TNFi: antibiotics, 2.6 ± 3.2 to 3.2 ± 3.5 (P < 0.001); antivirals, 0.06 ± 0.5 to 0.16 ± 0.7 (P = 0.004); and antimycotics, 0.14 ± 0.5 to 0.22 ± 0.9 (P = 0.06). The 12-month mean NP was highest in the second year after TNFi initiation (1.9 ± 2.4). No association was found between NP and glucocorticoids, age, body mass index, or pre-TNFi Disease Activity Score 28-joint count and C-reactive protein.
Conclusion: Patients with RA on TNFi are more commonly treated for infections in the outpatient settings than previously reported. Patients are prescribed more antimicrobials in the 2 years preceding TNFi initiation than the general population, and this use further increases after initiation of TNFi. In contrast to what is reported for infections requiring hospitalization, outpatient antimicrobial use remained elevated for at least 2 years.Landspitali University Hospital Research Fun
Breast and Prostate Cancer Risks for Male BRCA1 and BRCA2 Pathogenic Variant Carriers Using Polygenic Risk Scores.
Full text linkTo 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: Recent population-based female breast cancer and prostate cancer polygenic risk scores (PRS) have been developed. We assessed the associations of these PRS with breast and prostate cancer risks for male BRCA1 and BRCA2 pathogenic variant carriers.
Methods: 483 BRCA1 and 1318 BRCA2 European ancestry male carriers were available from the Consortium of Investigators of Modifiers of BRCA1/2 (CIMBA). A 147-single nucleotide polymorphism (SNP) prostate cancer PRS (PRSPC) and a 313-SNP breast cancer PRS were evaluated. There were 3 versions of the breast cancer PRS, optimized to predict overall (PRSBC), estrogen receptor (ER)-negative (PRSER-), or ER-positive (PRSER+) breast cancer risk.
Results: PRSER+ yielded the strongest association with breast cancer risk. The odds ratios (ORs) per PRSER+ standard deviation estimates were 1.40 (95% confidence interval [CI] =1.07 to 1.83) for BRCA1 and 1.33 (95% CI = 1.16 to 1.52) for BRCA2 carriers. PRSPC was associated with prostate cancer risk for BRCA1 (OR = 1.73, 95% CI = 1.28 to 2.33) and BRCA2 (OR = 1.60, 95% CI = 1.34 to 1.91) carriers. The estimated breast cancer odds ratios were larger after adjusting for female relative breast cancer family history. By age 85 years, for BRCA2 carriers, the breast cancer risk varied from 7.7% to 18.4% and prostate cancer risk from 34.1% to 87.6% between the 5th and 95th percentiles of the PRS distributions.
Conclusions: Population-based prostate and female breast cancer PRS are associated with a wide range of absolute breast and prostate cancer risks for male BRCA1 and BRCA2 carriers. These findings warrant further investigation aimed at providing personalized cancer risks for male carriers and informing clinical management
The occurrence of multiple treatment switches in axial spondyloarthritis. Results from five Nordic rheumatology registries.
No full textTo access publisher's full text version of this article click on the hyperlink belowObjectives: In axial spondyloarthritis (axSpA), switching between multiple biologic or targeted synthetic (b/ts-) DMARDs might indicate difficult-to-treat disease. We aimed to explore the occurrence of multiple switching in routine care axSpA patients using various definitions, and to identify associated clinical characteristics upon start of first b/tsDMARD (baseline).
Methods: Observational cohort study including patients with axSpA starting a first-ever b/tsDMARD 2009-2018 based on data from five biologic registries (Denmark/Sweden/Finland/Norway/Iceland). Comorbidities and extra-articular manifestations were identified through linkage to national registries. Multi-switching was defined in overlapping categories according to b/tsDMARD treatment history: treatment with ≥3 b/tsDMARDs, ≥4 or ≥ 5 b/tsDMARDs during follow-up. We explored the cumulative incidence of patients becoming multi-switchers with ≥3 b/tsDMARDs stratified by calendar-period (2009-11/2012-13/2014-15/2016-2018). In the subgroup of patients starting a first b/tsDMARD 2009-2015, baseline characteristics associated with multi-switching (within 3 years' follow-up) were explored using multiple logistic regression analyses.
Results: Among 8,398 patients included, 6,056 patients (63% male, median age 42 years) started a first b/tsDMARD 2009-2015, whereof proportions treated with ≥3, ≥4 or ≥ 5 b/tsDMARDs within 3 years' follow-up were 8%, 3%, 1%, respectively.Calendar-period did not affect the cumulative incidence of multi-switching.Baseline characteristics associated with multi-switching (≥3 b/tsDMARDs) were female gender, shorter disease duration, higher patient global score, comorbidities, and having psoriasis but not uveitis.
Conclusion: In this large Nordic observational cohort of axSpA patients, multiple switching was frequent with no apparent time-trend. Clinical associated factors included gender, but also previous comorbidities and extraarticular manifestations illustrating the ongoing challenge of treating this patient group.
Keywords: Biological treatment; axial spondyloarthritis; registry; routine care; switching.NordFors
Þjónandi forysta: Árangursrík stjórnun í heilbrigðisþjónustu
Full text linkTo 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 DownloadHér á eftir verður fjallað um hugmyndafræði þjónandi forystu
og leitað svara við spurningunni: Hvað er þjónandi forysta og
hentar hún í heilbrigðiskerfinu?
Helstu hugtökum verða gerð skil auk þess sem fjallað verður
um mælitæki sem notað er við gerð rannsókna á þessu
sviði. Fjallað verður um þjónandi forystu sem stjórnunarstíl
innan heilbrigðiskerfisins og áhrif þjónandi forystu á
hjúkrunarfræðinga, bæði sem stjórnendur og undirmenn.
Helsta gagnrýni á þjónandi forystu sem stjórnunarstíl verða
einnig tekin til skoðunar