Acute thoracic aortic dissection (ATAD) is a devastating condition associated with a high mortality rate. Recent reports suggest that its incidence is rising. Utilizing nationwide data comprising the ...whole Icelandic population, we aimed to determine the incidence, mortality rate and time-dependent mortality risk of ATAD.
Data were retrospectively collected using centralized hospital discharge registries, autopsy records and Cause of Death Registry in Iceland from 1992 to 2013.
Age- and gender-adjusted incidence of ATAD was 2.53/100 000/year, and no significant change in incidence was observed during the study period. The mean age was 66.9 ± 13.6 years and 66.0% (101/153) were Stanford type A. Of the whole group, 17.6% (27/153) died prior to hospital arrival, whereas the risk of death for patients who arrived alive to a hospital was 21.4% (27/126) within 24 h and 45.2% (57/126) at 30 days. During the course of the study, patients with type A dissection were more likely to undergo an operation and the management of type B dissection changed from open to endovascular repair. The 30-day mortality rate declined every year and the 5-year survival rate improved in the last third of the study.
The incidence of ATAD was 2.53/100 000/year and remained constant throughout the study, contradicting recent perceptions of a rising incidence. ATAD, type A in particular, remains a highly lethal condition: Over half of all patients die within 30 days of the index event. A reduced 30-day mortality rate and an increased long-term survival rate indicate improved overall outcomes in patients with this complex condition.
Most epidemiological studies on chronic kidney disease (CKD) are based solely on estimated glomerular filtration rate (eGFR). Few studies have included proteinuria, while the chronicity criterion is ...usually omitted. To explore this, we examined the prevalence of CKD stages 1-5 in Iceland based on multiple markers of kidney damage. All serum creatinine values, urine protein measurements and diagnostic codes for kidney diseases and comorbid conditions for people aged 18 years and older were obtained from electronic medical records of all healthcare institutions in Iceland in 2008-2016. CKD was defined according to the Kidney Disease: Improving Global Outcomes (KDIGO) clinical practice guideline using diagnoses indicative of a chronic kidney disease, proteinuria and/or an eGFR under 60 mL/min/1.73 m2 for over three months. Mean annual age-standardized prevalence of CKD stages 1-5 was calculated based on the KDIGO criteria and age-adapted eGFR thresholds from 2,120,147 creatinine values for 218,437 individuals, 306,531 proteinuria measurements for 86,364 individuals and 6973 individuals carrying a kidney disease diagnosis. Median age was 63 years (range, 18–106) and 47% were male. The mean annual age standardized CKD prevalence was 5.13% for men and 6.75% for women using the KDIGO criteria but by age-adapted eGFR cut-offs, the prevalence was 3.27% for men and 4.01% for women. Thus, our nationwide study, defining CKD in Iceland with strict adherence to the KDIGO criteria, demonstrates a lower prevalence of CKD than anticipated from most previous studies.
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Objective
The level of cartilage acidic protein 1 (CRTAC1) in plasma was recently discovered to be associated with osteoarthritis (OA) risk and progression to joint replacement in Iceland. This study ...was undertaken to validate these findings in an independent population.
Methods
In this study, 1,462 plasma proteins were measured in 54,265 participants from the UK Biobank on the Olink Explore platform. We analyzed the association of plasma proteins with prevalent OA, incident OA, and progression to joint replacement. We assessed the specificity of OA association through comparison of associations with inflammatory joint diseases and with previous joint replacement.
Results
The CRTAC1 protein showed the strongest association with prevalent knee OA (odds ratio OR 1.34 95% confidence interval (95% CI) 1.27, 1.41) and was associated with hip OA (OR 1.19 95% CI 1.11, 1.28). It predicted incident diagnosis of OA in the knee (hazard ratio HR 1.40 95% CI 1.35, 1.46) and hip (HR 1.25 95% CI 1.19, 1.31), as well as progression to joint replacement (HR 1.20 95% CI 1.08, 1.33 for the knee and HR 1.22 95% CI 1.08, 1.38 for the hip), while no association was found with inflammatory joint diseases. Individuals in the highest quintile of risk based on CRTAC1 level, age, sex, and body mass index had a 10‐fold risk of knee or hip OA within 5 years compared to those in the lowest quintile. Adding aggrecan core protein (ACAN) and neurocan core protein (NCAN) to the model improved the prediction of OA but not joint replacement. Furthermore, we replicated the association of CUB domain–containing protein 1 with prior joint replacement.
Conclusion
Plasma CRTAC1 is a specific biomarker for OA and a predictor of OA risk and progression to joint replacement. Adding ACAN and NCAN protein levels to the CRTAC1 model improved the prediction of OA.
Osteoarthritis has a highly negative impact on quality of life because of the associated pain and loss of joint function. Here we describe the largest meta-analysis so far of osteoarthritis of the ...hip and the knee in samples from Iceland and the UK Biobank (including 17,151 hip osteoarthritis patients, 23,877 knee osteoarthritis patients, and more than 562,000 controls). We found 23 independent associations at 22 loci in the additive meta-analyses, of which 16 of the loci were novel: 12 for hip and 4 for knee osteoarthritis. Two associations are between rare or low-frequency missense variants and hip osteoarthritis, affecting the genes SMO (rs143083812, frequency 0.11%, odds ratio (OR) = 2.8, P = 7.9 × 10
, p.Arg173Cys) and IL11 (rs4252548, frequency 2.08%, OR = 1.30, P = 2.1 × 10
, p.Arg112His). A common missense variant in the COL11A1 gene also associates with hip osteoarthritis (rs3753841, frequency 61%, P = 5.2 × 10
, OR = 1.08, p.Pro1284Leu). In addition, using a recessive model, we confirm an association between hip osteoarthritis and a variant of CHADL
(rs117018441, P = 1.8 × 10
, OR = 5.9). Furthermore, we observe a complex relationship between height and risk of osteoarthritis.
Autoimmune thyroid disease is the most common autoimmune disease and is highly heritable
. Here, by using a genome-wide association study of 30,234 cases and 725,172 controls from Iceland and the UK ...Biobank, we find 99 sequence variants at 93 loci, of which 84 variants are previously unreported
. A low-frequency (1.36%) intronic variant in FLT3 (rs76428106-C) has the largest effect on risk of autoimmune thyroid disease (odds ratio (OR) = 1.46, P = 2.37 × 10
). rs76428106-C is also associated with systemic lupus erythematosus (OR = 1.90, P = 6.46 × 10
), rheumatoid factor and/or anti-CCP-positive rheumatoid arthritis (OR = 1.41, P = 4.31 × 10
) and coeliac disease (OR = 1.62, P = 1.20 × 10
). FLT3 encodes fms-related tyrosine kinase 3, a receptor that regulates haematopoietic progenitor and dendritic cells. RNA sequencing revealed that rs76428106-C generates a cryptic splice site, which introduces a stop codon in 30% of transcripts that are predicted to encode a truncated protein, which lacks its tyrosine kinase domains. Each copy of rs76428106-C doubles the plasma levels of the FTL3 ligand. Activating somatic mutations in FLT3 are associated with acute myeloid leukaemia
with a poor prognosis and rs76428106-C also predisposes individuals to acute myeloid leukaemia (OR = 1.90, P = 5.40 × 10
). Thus, a predicted loss-of-function germline mutation in FLT3 causes a reduction in full-length FLT3, with a compensatory increase in the levels of its ligand and an increased disease risk, similar to that of a gain-of-function mutation.
The etiology of monoclonal gammopathy of undetermined significance (MGUS), the precursor state of multiple myeloma (MM), is mostly unknown and no studies have been conducted on the effect of diet on ...MGUS or progression from MGUS to MM. We aimed to explore the association between common foods and MGUS and progression to MM. Data from the population-based AGES Study (N = 5,764) were utilized. Food frequency questionnaire was used to assess dietary intake during adolescence, midlife, and late life. Serum protein electrophoresis and serum free light-chain assay was performed to identify MGUS (n = 300) and LC-MGUS cases (n = 275). We cross linked our data with the Icelandic Cancer Registry to find cases of MM in the study group. We found that intake of fruit at least three times per week during adolescence was associated with lower risk of MGUS when compared to lower fruit consumption (OR = 0.62, 95% CI 0.41-0.95). We additionally found that intake of fruit at least three times per week during the late life period was associated with decreased risk of progressing from MGUS to MM (HR = 0.34, 95% CI 0.13-0.89) when compared to lower intake. Adolescent intake of fruit may reduce risk of MGUS, whereas fruit intake after MGUS onset may reduce risk of progressing to MM. Our findings suggest that diet might alter the risk of developing MGUS and progression to MM.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
High-throughput proteomics platforms measuring thousands of proteins in plasma combined with genomic and phenotypic information have the power to bridge the gap between the genome and diseases. Here ...we performed association studies of Olink Explore 3072 data generated by the UK Biobank Pharma Proteomics Project
on plasma samples from more than 50,000 UK Biobank participants with phenotypic and genotypic data, stratifying on British or Irish, African and South Asian ancestries. We compared the results with those of a SomaScan v4 study on plasma from 36,000 Icelandic people
, for 1,514 of whom Olink data were also available. We found modest correlation between the two platforms. Although cis protein quantitative trait loci were detected for a similar absolute number of assays on the two platforms (2,101 on Olink versus 2,120 on SomaScan), the proportion of assays with such supporting evidence for assay performance was higher on the Olink platform (72% versus 43%). A considerable number of proteins had genomic associations that differed between the platforms. We provide examples where differences between platforms may influence conclusions drawn from the integration of protein levels with the study of diseases. We demonstrate how leveraging the diverse ancestries of participants in the UK Biobank helps to detect novel associations and refine genomic location. Our results show the value of the information provided by the two most commonly used high-throughput proteomics platforms and demonstrate the differences between them that at times provides useful complementarity.
Objective
Biomarkers for diagnosis and progression of osteoarthritis (OA) are lacking. This study was undertaken to identify circulating biomarkers for OA that could predict disease occurrence and/or ...progression to joint replacement.
Methods
Using the SomaScan platform, we measured 4,792 proteins in plasma from 37,278 individuals, of whom 12,178 individuals had OA and 2,524 had undergone joint replacement. We performed a case–control study for identification of potential protein biomarkers for hip, knee, and/or hand OA, and a prospective study for identification of biomarkers for joint replacement.
Results
Among the large panel of plasma proteins assessed, cartilage acidic protein 1 (CRTAC1) was the most strongly associated with both OA diagnosis (odds ratio 1.46 95% confidence interval 1.41–1.52 for knee OA, odds ratio 1.36 95% confidence interval 1.29–1.43 for hip OA, and odds ratio 1.33 95% confidence interval 1.26–1.40 for hand OA) and progression to joint replacement (hazard ratio 1.40 95% confidence interval 1.30–1.51 for knee replacement and hazard ratio 1.31 95% confidence interval 1.19–1.45 for hip replacement). Patients with OA who were in the highest quintile of risk of joint replacement, based on known risk factors (i.e., age, sex, and body mass index) and plasma CRTAC1 level, were 16 times more likely to undergo knee replacement within 5 years of plasma sample collection than those in the lowest quintile, and 6.5 times more likely to undergo hip replacement. CRTAC1 was not associated with other types of inflammatory arthritis. A specific protein profile was identified in those patients who had undergone joint replacement prior to plasma sample collection.
Conclusion
Through a hypothesis‐free approach, we identified CRTAC1 in plasma as a novel promising candidate biomarker for OA that is both associated with occurrence of OA and predictive of progression to joint replacement. This biomarker might also be useful in the selection of suitable patients for clinical trial enrollment.
Abstract
Background
Neuroinflammation has gained increasing attention as a potential contributing factor in the onset and progression of Alzheimer’s disease (AD). The objective of this study was to ...examine the association of selected cerebrospinal fluid (CSF) inflammatory and neuronal degeneration markers with signature CSF AD profile and cognitive functions among subjects at the symptomatic pre- and early dementia stages.
Methods
In this cross-sectional study, 52 subjects were selected from an Icelandic memory clinic cohort. Subjects were classified as having AD (
n
= 28, age = 70, 39% female, Mini-Mental State Examination MMSE = 27) or non-AD (
n
= 24, age = 67, 33% female, MMSE = 28) profile based on the ratio between CSF total-tau (T-tau) and amyloid-β
1–42
(Aβ
42
) values (cut-off point chosen as 0.52). Novel CSF biomarkers included neurofilament light (NFL), YKL-40, S100 calcium-binding protein B (S100B) and glial fibrillary acidic protein (GFAP), measured with enzyme-linked immunosorbent assays (ELISAs). Subjects underwent neuropsychological assessment for evaluation of different cognitive domains, including verbal episodic memory, non-verbal episodic memory, language, processing speed, and executive functions.
Results
Accuracy coefficient for distinguishing between the two CSF profiles was calculated for each CSF marker and test. Novel CSF markers performed poorly (area under curve AUC coefficients ranging from 0.61 to 0.64) compared to tests reflecting verbal episodic memory, which all performed fair (AUC > 70). LASSO regression with a stability approach was applied for the selection of CSF markers and demographic variables predicting performance on each cognitive domain, both among all subjects and only those with a CSF AD profile. Relationships between CSF markers and cognitive domains, where the CSF marker reached stability selection criteria of > 75%, were visualized with scatter plots. Before calculations of corresponding Pearson’s correlations coefficients, composite scores for cognitive domains were adjusted for age and education. GFAP correlated with executive functions (
r
= − 0.37,
p
= 0.01) overall, while GFAP correlated with processing speed (
r
= − 0.68,
p
< 0.001) and NFL with verbal episodic memory (
r
= − 0.43,
p
= 0.02) among subjects with a CSF AD profile.
Conclusions
The novel CSF markers NFL and GFAP show potential as markers for cognitive decline among individuals with core AD pathology at the symptomatic pre- and early stages of dementia.
Hypoxic hepatitis (HH) is an important clinical entity in patients in the intensive care unit (ICU). The aims of the study were to assess the etiology, clinical characteristics and outcomes of HH in ...the ICU of a tertiary hospital. Secondary aim was to analyze the effects of concomitant ischemia in other organs than the liver.
All patients with HH, 2011-2018, in a university hospital ICU were included. Data were collected on etiology, relevant clinical data and outcome. HH was defined by an increase in aminotransferases ≥10 times the upper limit of normal within 48 h from a clinical event of cardiac, circulatory or respiratory failure. Other causes of liver cell necrosis were excluded.
Of 9,931 patients hospitalized in the ICU, 159 (1.6%) fulfilled criteria for HH. In-hospital mortality occurred in 85 (53%) and 60 (38%) survived one year. Median ICU stay was five days (interquartile range (IQR) 3-10) and median hospital stay 16 days (IQR 7-32). Shock (48%), cardiac arrest (25%) and hypoxia (13%) were the most common causes of HH. Acute kidney injury (81%), rhabdomyolysis (50%), intestinal ischemia (6%) and ischemic pancreatitis (3%) occurred concomitantly. Age (odds ratio (OR) 1.05 (95% CI 1.02-1.09)), serum lactate (OR 2.61 (95% CI 1.23-5.50)) and lactate dehydrogenase (OR 1.14 (95% CI 1.02-1.27)) were predictors of mortality.
Hypoxic hepatitis was related to shock in approximately 50% of cases and associated with high in-hospital mortality. HH was commonly associated with ischemia in other organs. In-hospital mortality was associated with age, lactate and LD.
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