Long-term risk of heart failure and other adverse cardiovascular outcomes in primary Sjögren's syndrome.

BACKGROUND: Data on long-term cardiovascular outcomes in primary Sjögren's syndrome (PSS) are scarce. OBJECTIVES: We aim to investigate the long-term rate of incident heart failure (HF) and other adverse cardiovascular endpoints in patients with PSS compared with the general population and to investigate mortality in individuals with incident HF with or without a history of PSS. METHODS: Using Danish nationwide registries, PSS patients (diagnosed 1996-2018) without a history of other autoimmune diseases were each matched with four individuals from the general population by sex, age, and comorbidities. Multivariable Cox regression was used to estimate the rate of cardiovascular outcomes. In addition, the rate of death from any cause was compared between PSS patients with incident HF and four age- and sex-matched HF patients without PSS. RESULTS: In total, 5092 patients with newly diagnosed PSS were matched with 20,368 individuals from the general population (median age 57 years, 87.3% women, median follow-up 7.4 years). The cumulative incidence of HF at 10 years was 4.0% for PSS patients and 2.8% for matched individuals. After adjustment, patients with PSS had a higher associated rate of incident HF (hazard ratios [HR] 1.42 [95% CI, 1.20-1.68]) and other cardiovascular outcomes, compared with the background population. PSS patients with incident HF had a similar rate of death from all-cause mortality compared with HF patients without PSS (HR 0.94 [0.74-1.19]). CONCLUSIONS: Patients with PSS had a higher associated rate of incident HF and other cardiovascular outcomes compared with the general population. In individuals with incident HF, a history of PSS was not associated with increased mortality.

Gender- and age-specific rates of heart failure and other adverse cardiovascular outcomes in systemic sclerosis.

OBJECTIVE: To investigate the long-term rates of heart failure (HF) and other adverse cardiovascular outcomes, including arrhythmias, myocardial infarction, ischaemic stroke, venous thromboembolism, pulmonary hypertension and pericarditis, in SSc patients according to gender and age. METHODS: Using Danish nationwide registries, SSc patients (diagnosed from 1996 to 2018) were matched with four controls from the background population by gender, age and comorbidities. Cox regression was used to compare the rates of cardiovascular outcomes between SSc patients and controls and the rate of mortality between SSc patients developing HF and HF patients without SSc, according to gender and age (above/below median). RESULTS: In total, 1569 SSc patients were matched with 6276 non-SSc controls (median age 55 years, 80.4% women, median follow-up 7.3 years). SSc had a higher rate of HF in both women [HR 2.99 (95% CI 2.18, 4.09)] and men [HR 3.01 (1.83, 4.95)] (Pinteraction = 0.88), with similar trends for other cardiovascular outcomes. SSc had a higher rate of HF in patients <55 years of age [HR 4.14 (95% CI 2.54, 6.74)] and ≥55 years [HR 2.74 (1.98, 3.78)] (Pinteraction = 0.22), with similar trends for other cardiovascular outcomes. SSc patients with new-onset HF had a higher rate of mortality than HF patients without a history of SSc, irrespective of gender (Pinteraction = 0.53) and age (Pinteraction = 0.43). CONCLUSIONS: SSc was associated with higher rates of HF and other cardiovascular outcomes than matched controls, irrespective of gender and age. Among patients with new-onset HF, a history of SSc was associated with higher mortality.

A risk score predicting unplanned renal replacement therapy after coronary catheterization.

BACKGROUND: Iodinated contrast medium exposure is associated with acute kidney injury (AKI). Patients with severe contrast-induced AKI (CI-AKI) may need renal replacement therapy (RRT). Prediction models exist for CI-AKI, but few need RRT. We aimed to establish a preprocedural score model to stratify patients at risk of unplanned postprocedural RRT following invasive coronary angiography (ICA) or percutaneous coronary intervention (PCI). METHODS AND RESULTS: Between January 2010 and December 2015, a series of 3,469 patients were randomly divided into two cohorts at a 2 : 1 ratio for model development and validation, respectively. A total of 36 patients (1.0%) needed unplanned postprocedural RRT following ICA and/or PCI. Multivariable logistic regression was used to build the risk model. C-statistic and Hosmer-Lemeshow tests were used to evaluate the performance of the model. Five preprocedural variables - independently associated with unplanned postprocedural RRT - were identified as factors of the risk score model with different scores: age > 75 years (1), serum creatinine level ≥ 1.5 mg/dL (1), diabetes mellitus (1), hypotension (2), and acute myocardial infarction (2). The risk score model was demonstrated with high discrimination (C-statistic = 0.872) and goodness of fit (χ2 = 3.769, p = 0.438). Furthermore, the model allowed a hierarchical classification of low, intermediate, and high risk, within which the observed unplanned RRT rates were ~ 0.4, 3.0, and 20.0%, respectively. CONCLUSION: Using preprocedural variables, we developed and validated a risk model for unplanned postprocedural RRT following ICA and/or PCI.

Downregulation of lncRNA XIST Represses Tumor Growth and Boosts Radiosensitivity of Neuroblastoma via Modulation of the miR-375/L1CAM Axis.

Neuroblastoma (NB) is a heterogeneous tumor that is common in infants and young children. Long non-coding RNA X-inactive specific transcript (XIST) is implicated in NB advancement. Nevertheless, the role and regulatory mechanism by which XIST in NB are not fully elucidated. Expression levels of XIST, microRNA-375-5p (miR-375), and L1 cell adhesion molecular (L1CAM) were examined through quantitative real-time polymerase chain reaction (qRT-PCR). The cell cycle progression, proliferation, and colony formation of NB cells were determined with flow cytometry, 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide (MTT), or cell colony formation assays. Cell apoptotic rate was detected with flow cytometry assay. The relationship between XIST or L1CAM and miR-375 was verified via dual-luciferase reporter assay. The level of L1CAM protein was examined through western blotting. The role of XIST in vivo was confirmed through xenograft assay. XIST and L1CAM were upregulated while miR-375 was downregulated in NB tissues and cells. XIST depletion repressed tumor growth in vivo and elevated radiosensitivity, arrested cell cycle progression, and impeded proliferation of NB cells in vitro. Mechanistically, XIST modulated L1CAM expression through competitively binding to miR-375. Furthermore, miR-375 inhibitor recovered XIST inhibition-mediated effects on the radiosensitivity and malignant behaviors of NB cells. Also, L1CAM overexpression reversed the effects of miR-375 enhancement on the cell cycle progression, proliferation, and radiosensitivity of NB cells. XIST downregulation repressed tumor growth and boosted radiosensitivity of NB via modulating the miR-375/L1CAM axis, indicating that XIST was a promising target for NB treatment.

A prediction model of contrast-associated acute kidney injury in patients with hypoalbuminemia undergoing coronary angiography.

BACKGROUND: Risk stratification is recommended as the key step to prevent contrast-associated acute kidney injury (CA-AKI) among at-risk patients following coronary angiography (CAG) and/or percutaneous coronary intervention (PCI). Patients with hypoalbuminemia are prone to CA-AKI and do not have their own risk stratification tool. Therefore, this study developed and validated a new model for predicting CA-AKI among hypoalbuminemia patients CAG/PCI. METHODS: 1272 patients with hypoalbuminemia receiving CAG/PCI were enrolled and randomly allocated (2:1 ratio) into the development cohort (n = 848) and the validation cohort (n = 424). CA-AKI was defined as an increase of ≥0.3 mg/dL or 50% in serum creatinine (SCr) compared to baseline in the 48 to 72 h after CAG/PCI. A prediction model was established with independent predictors according to stepwise logistic regression, showing as a nomogram. The discrimination of the new model was evaluated by the area under the curve (AUC) and was compared to the classic Mehran CA-AKI model. The Hosmer-Lemeshow test was conducted to assess the calibration of our model. RESULTS: Overall, 8.4% (71/848) patients of the development group and 11.2% (48/424) patients of the validation group experienced CA-AKI. A new nomogram included estimated glomerular filtration rate (eGFR), serum albumin (ALB), age and the use of intra-aortic balloon pump (IABP); showed better predictive ability than the Mehran score (C-index 0.756 vs. 0.693, p = 0.02); and had good calibration (Hosmer-Lemeshow test p = 0.187). CONCLUSIONS: We developed a simple model for predicting CA-AKI among patients with hypoalbuminemia undergoing CAG/PCI, but our findings need validating externally. TRIAL REGISTRATION: http://www.ClinicalTrials.gov NCT01400295 , retrospectively registered 21 July 2011.

Population attributable risk estimates of risk factors for contrast-induced acute kidney injury following coronary angiography: a cohort study.

BACKGROUND: Contrast-induced acute kidney injury (CI-AKI) is a common complication with poor outcomes following coronary angiography (CAG) or percutaneous coronary intervention (PCI). However, no study has explored the population attributable risks (PARs) of the CI-AKI risk factors. Therefore, we aimed to identify the independent risk factors of CI-AKI and estimate their PARs. METHODS: We analyzed 3450 consecutive patients undergoing CAG/PCI from a prospective cohort in Guangdong Provincial People's Hospital. CI-AKI was defined as a serum creatinine elevation ≥50% or 0.3 mg/dL from baseline within the first 48 to 72 h after the procedure. Independent risk factors for CI-AKI were evaluated through stepwise approach and multivariable logistic regression analysis, and those that are potentially modifiable were of interest. PARs of independent risk factors were calculated with their odds ratios and prevalence among our cohort. RESULTS: The overall incidence of CI-AKI was 7.19% (n = 248), which was associated with increased long-term mortality. Independent risk factors for CI-AKI included heart failure (HF) symptoms, hypoalbuminemia, high contrast volume, hypotension, hypertension, chronic kidney disease stages, acute myocardial infarction and age > 75 years. Among the four risk factors of interest, the PAR of HF symptoms was the highest (38.06%), followed by hypoalbuminemia (17.69%), high contrast volume (12.91%) and hypotension (4.21%). CONCLUSIONS: These modifiable risk factors (e.g., HF symptoms, hypoalbuminemia) could be important and cost-effective targets for prevention and treatment strategies to reduce the risk of CI-AKI. Intervention studies targeting these risk factors are needed.

Characteristics and requirements of hypertensive patients willing to use digital health tools in the Chinese community: a multicentre cross-sectional survey.

BACKGROUND: Digital health tools (WeChat or mobile health apps) provide opportunities for new methods of hypertension management for hypertensive patients. However, the willingness of these patients to use social media and mobile health apps for hypertension management remains unclear. This study explored the characteristics and requirements of patients willing to use digital health (WDH) tools to manage hypertension. METHODS: From February to March 2018, we administered questionnaires to 1089 patients with hypertension at eight Chinese primary medical units. We assessed independent risk factors of WDH and requirement among WDH patients. RESULTS: Overall, 43% (465/1089) of participants were WDH patients, who were younger (58 ± 12 vs 61 ± 13 years) and had a greater proportion of employed individuals (31% vs 14%) and higher education levels (65% vs 52%) than the non-WDH patients (all P < 0.0001). After adjusting for other risk factors, higher education (OR: 0.52; 95% CI: 0.34-0.79), good medicine adherence (OR: 1.5; 95% CI: 1.0-2.3) and blood pressure self-monitoring (OR: 1.6; 95% CI: 1.2-2.3) remained significantly associated with WDH (all P < 0.05). WDH patients responded that digital health tools should try to provide a platform for blood pressure monitoring (42%), medication reminders (41%), hypertension knowledge (39%) and doctor-patient communication (32%). CONCLUSION: Our survey suggested that among hypertensive patients, willingness to use digital health tools was significantly associated with education, medicine adherence and blood pressure self-monitoring. Digital health tool developers and researchers should pay particular attention to recruiting older, less educated and unemployed patients with less willingness and who are less technologically savvy and research the requirements of WDH patients (blood pressure monitoring, medication reminders, and knowledge education) in the future.

Effects of intravenous hydration on risk of contrast induced nephropathy and in-hospital mortality in STEMI patients undergoing primary percutaneous coronary intervention: a systematic review and meta-analysis of randomized controlled trials.

BACKGROUND: The role of intravenous hydration at the time of primary percutaneous intervention (PCI) for ST-segment elevation myocardial infarction (STEMI) remains unclear. Guidelines are vague, supported by low level evidence, and hydration is used less often than other clinical settings.To perform a systematic review and meta-analysis of all randomized controlled trials assessing intravenous hydration compared with non-hydration for prevention of contrast induced nephropathy (CIN) and In-hospital mortality in patients with STEMI undergoing primary PCI. METHODS: Medline, EMBASE and the Cochrane Register were searched to September 2018. Included studies reported the incidence of CIN, In-hospital mortality, requirement for dialysis and heart failure. Relative risks with 95% confidence intervals (CIs) for individual trials were pooled using a random effects model. RESULTS: Three moderate quality trials were identified including 1074 patients. Overall, compared with no hydration, intravenous hydration significantly reduced the incidence of CIN by 42% (RR 0.58; 95% CI: 0.45 to 0.74, p < 0.001). The estimated effects upon all-cause mortality (RR 0.56; 95% CI: 0.30 to 1.02, p = 0.057) and the requirement for dialysis (RR 0.52, 95% CI 0.14-1.88, p = 0.462) were not statistically significant. The outcome of heart failure was not consistently reported. CONCLUSIONS: Intravenous hydration likely reduces the incidence of CIN in patients with STEMI undergoing primary PCI. However, for key clinical outcomes such as mortality, heart failure and dialysis the effect estimates were imprecise. Further high quality studies are needed to clarify the appropriate volume of fluid and effects on outcomes.

Clinical Implications of Contrast-Induced Nephropathy in Patients Without Baseline Renal Dysfunction Undergoing Coronary Angiography.

BACKGROUND: The clinical implications of different definitions of contrast-induced nephropathy (CIN) in patients without baseline renal dysfunction are not well defined. METHODS: Consecutive patients at a single centre without baseline renal dysfunction (estimated glomerular filtration rate, eGFR≥60ml/min/1.73m2) undergoing coronary angiography or percutaneous coronary intervention (PCI), were systematically evaluated for long-term risk of mortality following CIN using two broad definitions: an absolute increase from baseline in serum creatinine (SCr) ≥0.3mg/dl (mild to severe absolute CIN) and a relative increase from baseline of 25% (mild to severe relative CIN) within 72hours. RESULT: Of 2,823 subjects alive before discharge following coronary angiography there were 320 episodes of mild to severe relative CIN (11.3%) and 125 of mild to severe absolute CIN (4.4%). During a median follow-up of 2.3years, 73 patients (3.2%) died. After adjustment for confounders, mild to severe absolute CIN was associated with an adjusted hazard ratio (HR) (95% confidence interval) for all-cause mortality of 3.31 (1.74-6.30) (p<0.0001) and relative CIN with an adjusted HR of 1.92 (1.09, 3.38) (p=0.024). The risk of mortality rose with severity of CIN. Two commonly used definitions of CIN combining absolute and relative terms (increase ≥ 0.3mg/dl or 50%, and ≥ 0.5mg/dl or 25% from the baseline) confirmed these results. CONCLUSION: Among patients without baseline renal dysfunction undergoing coronary angiography, the incidence of CIN can range widely depending on definition. Absolute CIN is less common than relative CIN. Regardless of definition, CIN is associated with a markedly increased risk of long-term mortality. This finding requires confirmation in multicentre studies.

Optimizing sparse sequencing of single cells for highly multiplex copy number profiling.

Genome-wide analysis at the level of single cells has recently emerged as a powerful tool to dissect genome heterogeneity in cancer, neurobiology, and development. To be truly transformative, single-cell approaches must affordably accommodate large numbers of single cells. This is feasible in the case of copy number variation (CNV), because CNV determination requires only sparse sequence coverage. We have used a combination of bioinformatic and molecular approaches to optimize single-cell DNA amplification and library preparation for highly multiplexed sequencing, yielding a method that can produce genome-wide CNV profiles of up to a hundred individual cells on a single lane of an Illumina HiSeq instrument. We apply the method to human cancer cell lines and biopsied cancer tissue, thereby illustrating its efficiency, reproducibility, and power to reveal underlying genetic heterogeneity and clonal phylogeny. The capacity of the method to facilitate the rapid profiling of hundreds to thousands of single-cell genomes represents a key step in making single-cell profiling an easily accessible tool for studying cell lineage.

Population genetic structure is shaped by historical, geographic, and environmental factors in the leguminous shrub Caragana microphylla on the Inner Mongolia Plateau of China.

BACKGROUND: Understanding how landscape factors, including suites of geographic and environmental variables, and both historical and contemporary ecological and evolutionary processes shape the distribution of genetic diversity is a primary goal of landscape and conservation genetics and may be particularly consequential for species involved in ecological restoration. In this study, we examine the factors that shape the distribution of genetic variation in a leguminous shrub (Caragana microphylla) important for restoration efforts on the Mongolian Plateau in China. This region houses several major bioclimatic gradients, and C. microphylla is an important restoration species because it stabilizes soils and prevents advancing desertification on the Inner Mongolia Plateau caused by ongoing climate change. RESULTS: We assembled an expansive genomic dataset, consisting of 22 microsatellite loci, four cpDNA regions, and 5788 genome-wide SNPs from ten populations of C. microphylla. We then applied ecological niche modelling and linear and non-linear regression techniques to investigate the historical and contemporary forces that explain patterns of genetic diversity and population structure in C. microphylla on the Inner Mongolia Plateau. We found strong evidence that both geographic and environmental heterogeneity contribute to genetic differentiation and that the spatial distribution of genetic diversity in C. microphylla appears to result partly from the presence of a glacial refugium at the southwestern edge of its current range. CONCLUSIONS: These results suggest that geographic, environmental, and historical factors have all contributed to spatial genetic variation in this ecologically important species. These results should guide restoration plans to sustain genetic diversity during plant translocations.

Association of ADAM 12 polymorphisms with the risk of knee osteoarthritis: meta-analysis of 5048 cases and 6848 controls.

Several studies have suggested the association between ADAM 12 polymorphisms and the risk of osteoarthritis (OA), but the results remained controversial. Therefore, we designed a meta-analysis to systematically evaluate the association on this issue. A literature search for eligible studies was conducted in PubMed, Web of Science and Google Scholar databases. The association between ADAM 12 polymorphisms and knee OA risk was calculated by odds ratios (ORs) and 95% confidence intervals (CIs). Study heterogeneity, sensitivity and publication bias analyses were also conducted. Ten articles covering 5048 cases and 6848 controls met our criteria for the final analysis. We found that the rs1871054 was significantly associated with the risk of knee OA (allele model OR 1.72, 95% CI 1.43-2.07, P < 0.001; additive model: OR 2.06, 95% CI 1.19-3.56, P = 0.010; dominant model: OR 2.45, 95% CI 1.85-3.25, P < 0.001; recessive model: OR 1.54, 95% CI 1.13-2.10, P = 0.007). rs1044122 was significantly associated with knee OA susceptibility in recessive model (OR 1.45, 95% CI 1.03-2.04, P = 0.031). For rs3740199 and rs1278279, no significant associations with knee OA were found. In the stratified analysis by gender, significant association was identified with the risk of knee OA for rs3740199 in men in allele model (OR 2.41, 95% CI 1.51-3.84, P < 0.001), dominant model (OR 2.68, 95% CI 1.17-6.14, P = 0.02) and recessive model (OR 3.51, 95% CI 1.68-7.36, P = 0.001), but not for additive model (OR 1.30, 95% CI 0.81-2.08, P = 0.28). This meta-analysis suggests that the ADAM 12 genetic polymorphisms rs1871054 and rs1044122 might be associated with risk of knee OA; rs3740199 might be associated with risk of knee OA in men. Further well-designed and large scale studies are warranted to validate these associations.

Target inference from collections of genomic intervals.

Finding regions of the genome that are significantly recurrent in noisy data are a common but difficult problem in present day computational biology. Cores of recurrent events (CORE) is a computational approach to solving this problem that is based on a formalized notion by which "core" intervals explain the observed data, where the number of cores is the "depth" of the explanation. Given that formalization, we implement CORE as a combinatorial optimization procedure with depth chosen from considerations of statistical significance. An important feature of CORE is its ability to explain data with cores of widely varying lengths. We examine the performance of this system with synthetic data, and then provide two demonstrations of its utility with actual data. Applying CORE to a collection of DNA copy number profiles from single cells of a given tumor, we determine tumor population phylogeny and find the features that separate subpopulations. Applying CORE to comparative genomic hybridization data from a large set of tumor samples, we define regions of recurrent copy number aberration in breast cancer.

A splice donor mutation in NAA10 results in the dysregulation of the retinoic acid signalling pathway and causes Lenz microphthalmia syndrome.

INTRODUCTION: Lenz microphthalmia syndrome (LMS) is a genetically heterogeneous X-linked disorder characterised by microphthalmia/anophthalmia, skeletal abnormalities, genitourinary malformations, and anomalies of the digits, ears, and teeth. Intellectual disability and seizure disorders are seen in about 60% of affected males. To date, no gene has been identified for LMS in the microphthalmia syndrome 1 locus (MCOPS1). In this study, we aim to find the disease-causing gene for this condition. METHODS AND RESULTS: Using exome sequencing in a family with three affected brothers, we identified a mutation in the intron 7 splice donor site (c.471+2T→A) of the N-acetyltransferase NAA10 gene. NAA10 has been previously shown to be mutated in patients with Ogden syndrome, which is clinically distinct from LMS. Linkage studies for this family mapped the disease locus to Xq27-Xq28, which was consistent with the locus of NAA10. The mutation co-segregated with the phenotype and cDNA analysis showed aberrant transcripts. Patient fibroblasts lacked expression of full length NAA10 protein and displayed cell proliferation defects. Expression array studies showed significant dysregulation of genes associated with genetic forms of anophthalmia such as BMP4, STRA6, and downstream targets of BCOR and the canonical WNT pathway. In particular, STRA6 is a retinol binding protein receptor that mediates cellular uptake of retinol/vitamin A and plays a major role in regulating the retinoic acid signalling pathway. A retinol uptake assay showed that retinol uptake was decreased in patient cells. CONCLUSIONS: We conclude that the NAA10 mutation is the cause of LMS in this family, likely through the dysregulation of the retinoic acid signalling pathway.

Significant distinct branches of hierarchical trees: a framework for statistical analysis and applications to biological data.

BACKGROUND: One of the most common goals of hierarchical clustering is finding those branches of a tree that form quantifiably distinct data subtypes. Achieving this goal in a statistically meaningful way requires (a) a measure of distinctness of a branch and (b) a test to determine the significance of the observed measure, applicable to all branches and across multiple scales of dissimilarity. RESULTS: We formulate a method termed Tree Branches Evaluated Statistically for Tightness (TBEST) for identifying significantly distinct tree branches in hierarchical clusters. For each branch of the tree a measure of distinctness, or tightness, is defined as a rational function of heights, both of the branch and of its parent. A statistical procedure is then developed to determine the significance of the observed values of tightness. We test TBEST as a tool for tree-based data partitioning by applying it to five benchmark datasets, one of them synthetic and the other four each from a different area of biology. For each dataset there is a well-defined partition of the data into classes. In all test cases TBEST performs on par with or better than the existing techniques. CONCLUSIONS: Based on our benchmark analysis, TBEST is a tool of choice for detection of significantly distinct branches in hierarchical trees grown from biological data. An R language implementation of the method is available from the Comprehensive R Archive Network: http://www.cran.r-project.org/web/packages/TBEST/index.html.

Long-term Rate of Ventricular Arrhythmia in Autoimmune Disease.

AIMS: Although selected autoimmune diseases (AIDs) have been linked to an increased risk of ventricular arrhythmias (VAs), data on the long-term rate of VAs across the spectrum of AIDs are lacking. The aim of our study was to investigate the long-term rate of VAs (a composite of ventricular tachycardia, ventricular fibrillation, ventricular flutter, or cardiac arrest) in individuals with a history of 28 different AIDs. METHODS: Individuals diagnosed with an AID (2005-2018) were identified through Danish nationwide registries. Each patient with AID was matched with four individuals from the background population by age and sex. Multivariable Cox regression was used to compare the rate of VAs between the AIDs and background population, overall and according to individual AIDs. RESULTS: In total, 186,733 patients diagnosed with AIDs were matched with 746,932 individuals without AIDs (median age 55 years; 63% female; median follow-up 6.0 years). The 5-year cumulative incidence of VAs was 0.5% for patients with AIDs and 0.3% for matched individuals. Patients with any AIDs had a higher associated rate of VAs than matched individuals (HR 1.39 [95% CI, 1.29-1.49]). The highest HR was observed in patients with systemic sclerosis (3.86 [95% CI, 1.92-7.75]). The higher rate of VAs in patients with AIDs, compared with individuals from the background population, was more pronounced in patients without ischemic heart disease or heart failure/cardiomyopathy compared to those with these conditions (Pinteraction < 0.05). CONCLUSIONS: Despite a low cumulative incidence, patients with a history of AIDs had a higher relative rate of VAs than matched individuals.

In a large Danish nationwide study, we examined the risk of ventricular arrhythmias, which are serious and potentially life-threatening conditions, in patients with and without a history of autoimmune diseases. Patients with a history of any autoimmune disease had a higher risk of experiencing ventricular arrhythmias compared with age- and sex-matched individuals from the background population. This association was observed for most of the autoimmune diseases when examined individually. The higher rate of ventricular arrhythmias in patients with autoimmune diseases, compared with individuals from the background population, was relatively more pronounced in patients without a history of ischemic heart disease or heart failure/cardiomyopathy compared with individuals with a history of these conditions.

Long-Term Risk of VTE in Sarcoidosis: A Nationwide Cohort Study.

BACKGROUND: Chronic inflammation is increasingly recognized as a risk factor for VTE, but unlike other inflammatory diseases including systemic lupus erythematosus and rheumatoid arthritis, data on the risk of VTE in patients with sarcoidosis are sparse. RESEARCH QUESTION: Do patients with sarcoidosis have a higher long-term risk of VTE (pulmonary embolism or DVT, and each of these individually) compared with the background population? STUDY DESIGN AND METHODS: Using Danish nationwide registries, patients aged ≥ 18 years with newly diagnosed sarcoidosis (two or more inpatient/outpatient visits, 1996-2020) without prior VTE were matched 1:4 by age, sex, and comorbidities with individuals from the background population. The primary outcome was VTE. RESULTS: We included 14,742 patients with sarcoidosis and 58,968 matched individuals (median age, 44.7 years; 57.2% male). The median follow-up was 8.8 years. Absolute 10-year risks of outcomes for patients with sarcoidosis vs the background population were the following: VTE, 2.9% vs 1.6% (P < .0001), pulmonary embolism, 1.5% vs 0.7% (P < .0001), and DVT, 1.6% vs 1.0% (P < .0001), respectively. In multivariable Cox regression, sarcoidosis was associated with an increased rate of all outcomes in the first year after diagnosis (VTE: hazard ratio [HR], 4.94; 95% CI, 3.61-6.75) and after the first year (VTE: HR, 1.65; 95% CI, 1.45-1.87) compared with the background population. These associations persisted when excluding patients with a history of cancer and censoring patients with incident cancer during follow-up. Three-month mortality was not significantly different between patients with VTE with and without sarcoidosis (adjusted HR, 0.84; 95% CI, 0.61-1.15). INTERPRETATION: In this nationwide cohort study, sarcoidosis was associated with a higher long-term risk of VTE compared with a matched background population.

Mortality in heart failure with and without autoimmune disease.

AIMS: Autoimmune diseases (AIDs) are associated with a higher risk of heart failure (HF). However, data on the prognosis of HF patients with a history of AID are limited. The aim was to investigate the rates of all-cause mortality and HF hospitalization in a large, nationwide cohort of patient with HF according to a history of 29 AIDs. METHODS AND RESULTS: Using Danish nationwide registries, each HF patient (diagnosed 2000-18) with a history of AID was matched with four HF patients without AID by age, sex, and year of HF diagnosis. Rates of outcomes were compared by Cox regression models. The prevalence of AID in patients with HF was 10.7%. In total, 21 256 HF patients with a history of AID were matched with 85 024 HF patients without AID (median age 77 years; 58.9% female). During a median follow-up of 3.2 years, the incidence rates per 100 person-years for all-cause mortality were 17.1 (95% confidence interval, 16.9-17.4) and 14.4 (14.3-14.6) in patients with and without AID, respectively. The corresponding rates for HF hospitalization were 5.0 (4.9-5.1) and 5.2 (5.1-5.4), respectively. A history of AID was associated with higher rate of all-cause mortality [hazard ratio (HR) 1.14 (1.12-1.17)], but not HF hospitalization [HR 1.00 (0.96-1.04)] compared with no AID. CONCLUSIONS: In a nationwide cohort study, patients with HF and a history of AID had a higher associated rate of mortality than those without a history of AID.

This study examined the rates of all-cause mortality and hazard ratio (HF) hospitalization in a large, nationwide cohort of patient with HF with and without a history of 29 autoimmune diseases (AIDs). Among HF patients, a history of AID was associated with higher mortality. Further research elucidating the explanations for the observed excess mortality is needed. Among HF patients, a history of AID was not associated with higher HF hospitalization.

Rhizobia-Legume Symbiosis Increases Aluminum Resistance in Alfalfa.

Alfalfa is the most important forage legume with symbiotic nitrogen-fixing nodule in roots, but it is sensitive to aluminum (Al), which limits its plantation in acidic soils. One rhizobia clone of Sinorhizobium meliloti with Al tolerance (AT1) was isolated from the nodule in AlCl3-treated alfalfa roots. AT1 showed a higher growth rate than the standard rhizobia strain Sm1021 under Al-stressed conditions. Alfalfa growth was improved by inoculation with AT1 under Al-stressed conditions, with increased length and fresh weight in shoots and roots. High nitrogenase activity and pink effective nodules were obtained in AT1-inoculated plant roots under Al stress, with increased total nitrogen compared with the non-inoculated control. The application of exogenous NH4+-nitrogen increased the Al resistance in alfalfa. It is suggested that rhizobia's increase of the Al resistance in alfalfa is associated with its improved nitrogen status. Inoculation with Al-tolerant rhizobia is worth testing in an acidic field for improved alfalfa productivity.

Long-term Risk of Heart Failure and Other Adverse Cardiovascular Outcomes in Granulomatosis With Polyangiitis: A Nationwide Cohort Study.

OBJECTIVE: To examine the long-term rates of heart failure (HF) and other adverse cardiovascular (CV) outcomes in a nationwide cohort of patients diagnosed with granulomatosis with polyangiitis (GPA) compared with the general population. METHODS: Using Danish nationwide registries, patients with newly diagnosed GPA were identified and matched 1:4 by age, sex, and comorbidities with subjects from the general population. Outcomes were compared using Cox regression. Due to violation of the proportional hazard assumption, landmark analyses for the first year and from 1 year were performed. RESULTS: Of the 1923 patients with GPA, 1781 patients (median age 59 yrs, 47.9% men) were matched with 7124 subjects from the general population. The median follow-up was 6.4 years. The absolute 10-year risk of HF was 6.8% (95% CI 5.5-8.2%) for patients with GPA and 5.9% (5.3-6.6%) for the general population. During the first year after diagnosis, GPA was associated with a significantly higher rate of HF (hazard ratio [HR] 3.60, 95% CI, 2.28-5.67) and other adverse outcomes, including atrial fibrillation/flutter (HR 6.50, 95% CI 4.43-9.55) and ischemic stroke (HR 3.24, 95% CI 1.92-5.48), compared with the general population. After the first year, GPA was not associated with higher rates of HF or other CV outcomes compared with the general population, except atrial fibrillation/flutter (HR 1.38, 95% CI 1.12-1.70). CONCLUSION: During the first year after diagnosis, the rates of HF and other CV outcomes were higher in patients with GPA compared with the general population. However, after the first year, the rates of HF and other CV outcomes, except atrial fibrillation/flutter, were similar to those in the general population.