scholarly journals Hospital-treated infectious diseases and the risk of dementia: multicohort study with replication in the UK Biobank

2020 ◽  
Author(s):  
Pyry N Sipilä ◽  
Nelli Heikkilä ◽  
Joni V Lindbohm ◽  
Christian Hakulinen ◽  
Jussi Vahtera ◽  
...  
Keyword(s):  
Infectious Diseases ◽  
Bacterial Infections ◽  
Viral Infections ◽  
Uk Biobank ◽  
Gram Negative ◽  
Increased Risk ◽  
The Uk ◽  
Dementia Onset

SummaryBackgroundInfectious diseases have been hypothesised to increase the risk of dementia. However, the evidence is sparse, captures only a limited range of infectious diseases, and relies on short follow-up periods. We assessed a wide range of severe (hospital-treated) bacterial and viral infections and their subtypes as risk factors for dementia in three large cohorts followed up for almost two decades and replicated the main findings in the UK Biobank.MethodsFor primary analysis, we pooled individual-level data from three prospective cohort studies with a median follow up of 19 years (from 1986-2005 to 2012-2016) and a total of 273 125 dementia-free community-dwelling participants. The replication analysis with the UK Biobank was based on 492 146 individuals (median follow-up 9·0 years from 2006-2010 to 2018). We ascertained exposure to infectious diseases and their subtypes before dementia onset using linked records from national hospital inpatient registers. Incident dementia was identified from linked hospital inpatient and outpatient records, medication reimbursement entitlements, and death certificates.FindingsIn the primary analysis based on 5·3 million person-years at risk, 88 099 participants had a hospital-treated infection before dementia onset and 3064 developed dementia. Gram-negative bacterial infections (hazard ratio [HR] 1·64; 95% confidence interval [CI] 1·25–2·14) and herpesvirus infections (HR 1·96; 95% CI 1·31–2·93) were robustly associated with an increased risk of dementia. For these infections, the relative risk of dementia remained similar when reverse causation and ascertainment biases were minimised by assessing only new dementia cases that occurred more than 10 years after the infection, and when comorbidities and potential confounders were considered. The associations were replicated in the UK Biobank with stronger relations observed for vascular dementia than Alzheimer’s disease. In contrast to gram-negative bacterial and herpesvirus infections, the hazard ratio for all bacterial infections combined attenuated from 1·60 (95% CI 1·48–1·72) to 1·27 (95% CI 1·14–1·41) when bias was minimised. For all viral infections, the corresponding attenuation was from HR 1·63 (95% CI 1·32–2·00) to 1·19 (95% CI 0·87–1·62).InterpretationGram-negative bacterial infections and herpesvirus infections were associated with a moderately increased risk of dementia both in the short- and long-term. Hospital-treated bacterial and viral infections in general had only modest long-term associations with incident dementia.FundingUK Medical Research Council, US National Institute on Aging, NordForsk, Academy of Finland, Helsinki Institute of Life Science.Research in contextEvidence before this studyInfectious diseases have been hypothesised in the aetiology of dementia. We searched PubMed on 2 April 2020 for observational studies and systematic reviews using the search terms ((Alzheimer* OR dementia) AND infectio* AND ((systematic[sb]) OR (Observational Study[ptyp])) without restrictions on language or publication date. We also searched the reference lists and citations of relevant articles. In observational studies, infectious diseases in general and specific bacterial (sepsis, septicaemia, bacteraemia, pneumonia, osteomyelitis, urinary tract infection, cellulitis, syphilis, and Borrelia burgdorferi and Chlamydia pneumoniae infections) and viral infections (hepatitis C infection, HIV) are linked to an increased risk of dementia. Additionally, there was suggestive evidence for associations of herpesvirus infections, Toxoplasma gondii parasite infection, and poor oral health with dementia. However, no large-scale studies assessed a wide range of different types of infectious diseases systematically in a single analytical setting and with adequate control for potential sources of bias, such as reverse causation resulting from the systemic changes related to the preclinical stages of dementia that increase susceptibility to infectious diseases.Added value of this studyIn this multicohort study, the primary analysis was based on individual-level data from 273 125 dementia-free community-dwelling participants with a median follow-up of 19 years. We ascertained 528 different infectious diseases before dementia onset using national hospital inpatient records and categorised them by causative microorganism (bacteria, viruses), disease invasiveness (invasive vs localised bacterial infections), and subtype (extracellular vs intracellular lifestyle and cell wall structure of bacteria, and type of virus). When reverse causation was minimised by analysing only infections that occurred more than 10 years before dementia onset, the relative risk of dementia was modest for all bacterial infections combined (hazard ratio [HR] 1·27; 95% confidence interval [CI] 1·14–1·41) and for all viral infections combined (HR 1·19; 95% CI 0·87–1·62). The associations of bacterial infections with dementia did not differ by the invasiveness of the infection (invasive vs localised infections) or extracellular vs intracellular lifestyle of the causative microorganism. In analysis of specific diagnostic groups, robust and stronger long-term associations with dementia were observed for Gram-negative bacterial infections (HR 1·64, 95% CI 1·25–2·14 for full follow-up; HR 1·67, 95% CI 1·13–2·48 from year 10 onwards) and herpesvirus infections (HR 1·96, 95% CI 1.31–2.93 full follow-up; HR 1·92, 95% CI 1·11–3·32 from year 10 onwards). These associations remained after controlling for comorbidities and potential confounders and were replicated in an independent cohort of 492 146 individuals from the UK Biobank (median follow-up 9·0 years) with stronger relations observed for vascular dementia than Alzheimer’s disease.Implications of all the available evidenceGram-negative bacterial infections and herpesvirus infections seem to be robust long-term risk factors for dementia. Further mechanistic and molecular research is warranted to clarify the potential role of Gram-negative bacterial infections and herpesvirus in neurodegeneration and the aetiology of dementia.

Associations of ophthalmic and systemic conditions with incident dementia in the UK Biobank

2021 ◽  
pp. bjophthalmol-2021-319508
Author(s):  
Xianwen Shang ◽  
Zhuoting Zhu ◽  
Yu Huang ◽  
Xueli Zhang ◽  
Wei Wang ◽  
...  
Keyword(s):  
Heart Disease ◽  
Age Related Macular Degeneration ◽  
Hospital Inpatient ◽  
Uk Biobank ◽  
Age Related ◽  
Incident Dementia ◽  
Increased Risk ◽  
The Uk ◽  
Systemic Condition

AimsTo examine independent and interactive associations of ophthalmic and systemic conditions with incident dementia.MethodsOur analysis included 12 364 adults aged 55–73 years from the UK Biobank cohort. Participants were assessed between 2006 and 2010 at baseline and were followed up until the early of 2021. Incident dementia was ascertained using hospital inpatient, death records and self-reported data.ResultsOver 1 263 513 person-years of follow-up, 2304 cases of incident dementia were documented. The multivariable-adjusted HRs (95% CI) for dementia associated with age-related macular degeneration (AMD), cataract, diabetes-related eye disease (DRED) and glaucoma at baseline were 1.26 (1.05 to 1.52), 1.11 (1.00 to 1.24), 1.61 (1.30 to 2.00) and (1.07 (0.92 to 1.25), respectively. Diabetes, heart disease, stroke and depression at baseline were all associated with an increased risk of dementia. Of the combination of AMD and a systemic condition, AMD-diabetes was associated with the highest risk for incident dementia (HR (95% CI): 2.73 (1.79 to 4.17)). Individuals with cataract and a systemic condition were 1.19–2.29 times more likely to develop dementia compared with those without cataract and systemic conditions. The corresponding number for DRED and a systemic condition was 1.50–3.24. Diabetes, hypertension, heart disease, depression and stroke newly identified during follow-up mediated the association between cataract and incident dementia as well as the association between DRED and incident dementia.ConclusionsAMD, cataract and DRED but not glaucoma are associated with an increased risk of dementia. Individuals with both ophthalmic and systemic conditions are at higher risk of dementia compared with those with an ophthalmic or systemic condition only.

Associations of BMI and Serum Urate with Developing Dementia: A Prospective Cohort Study

2020 ◽  
Vol 105 (12) ◽  
pp. e4688-e4698
Author(s):  
Zhi Cao ◽  
Chenjie Xu ◽  
Hongxi Yang ◽  
Shu Li ◽  
Fusheng Xu ◽  
...  
Keyword(s):  
Body Mass Index ◽  
Cohort Study ◽  
Lower Risk ◽  
Serum Urate ◽  
Healthy Weight ◽  
Uk Biobank ◽  
Health Records ◽  
Increased Risk ◽  
The Uk

Abstract Context Recent studies have suggested that a higher body mass index (BMI) and serum urate levels were associated with a lower risk of developing dementia. However, these reverse relationships remain controversial, and whether serum urate and BMI confound each other is not well established. Objectives To investigate the independent associations of BMI and urate, as well as their interaction with the risk of developing dementia. Design and Settings We analyzed a cohort of 502 528 individuals derived from the UK Biobank that included people aged 37–73 years for whom BMI and urate were recorded between 2006 and 2010. Dementia was ascertained at follow-up using electronic health records. Results During a median of 8.1 years of follow-up, a total of 2138 participants developed dementia. People who were underweight had an increased risk of dementia (hazard ratio [HR] = 1.91, 95% confidence interval [CI]: 1.24–2.97) compared with people of a healthy weight. However, the risk of dementia continued to fall as weight increased, as those who were overweight and obese were 19% (HR = 0.81, 95%: 0.73–0.90) and 22% (HR = 0.78, 95% CI: 0.68–0.88) were less likely to develop dementia than people of a healthy weight. People in the highest quintile of urate were also associated with a 25% (HR = 0.75, 95% CI: 0.64–0.87) reduction in the risk of developing dementia compared with those who were in the lowest quintile. There was a significant multiplicative interaction between BMI and urate in relation to dementia (P for interaction = 0.004), and obesity strengthens the protective effect of serum urate on the risk of dementia. Conclusion Both BMI and urate are independent predictors of dementia, and there are inverse monotonic and dose-response associations of BMI and urate with dementia.

scholarly journals Fitness, Fatness, and Mortality in Men and Women From the UK Biobank: Prospective Cohort Study

2021 ◽  
Author(s):  
Jakob Tarp ◽  
Anders Grøntved ◽  
Miguel A. Sanchez‐Lastra ◽  
Knut Eirik Dalene ◽  
Ding Ding ◽  
...  
Keyword(s):  
Body Composition ◽  
Cardiorespiratory Fitness ◽  
Cox Regression ◽  
World Health ◽  
Uk Biobank ◽  
Men And Women ◽  
Increased Risk ◽  
All Cause Mortality ◽  
The Uk

Background Cardiorespiratory fitness may moderate the association between obesity and all‐cause mortality (ie, the “fat‐but‐fit” hypothesis), but unaddressed sources of bias are a concern. Methods and Results Cardiorespiratory fitness was estimated as watts per kilogram from a submaximal bicycle test in 77 169 men and women from the UK Biobank cohort and combined with World Health Organization standard body mass index categories, yielding 9 unique fitness‐fatness combinations. We also formed fitness‐fatness combinations based on bioimpedance as a direct measure of body composition. All‐cause mortality was ascertained from death registries. Multivariable‐adjusted Cox regression models were used to estimate hazard ratios and 95% CIs. We examined the association between fitness‐fatness combinations and all‐cause mortality in models with progressively more conservative approaches for accounting for reverse causation, misclassification of body composition, and confounding. Over a median follow‐up of 7.7 years, 1731 participants died. In our base model, unfit men and women had higher risk of premature mortality irrespective of levels of adiposity, compared with the normal weight–fit reference. This pattern was attenuated but maintained with more conservative approaches in men, but not in women. In analysis stratified by sex and excluding individuals with prevalent major chronic disease and short follow‐up and using direct measures of body composition, mortality risk was 1.78 (95% CI, 1.17–2.71) times higher in unfit‐obese men but not higher in obese‐fit men (0.94 [95% CI, 0.60–1.48]). In contrast, there was no increased risk in obese‐unfit women (1.09 [95% CI, 0.44–1.05]) as compared with the reference. Conclusions Cardiorespiratory fitness modified the association between obesity and mortality in men, but this pattern appeared susceptible to biases in women.

scholarly journals Women With Diabetes Are at Increased Relative Risk of Heart Failure Compared to Men: Insights From UK Biobank

2021 ◽  
Vol 8 ◽  
Author(s):  
Sucharitha Chadalavada ◽  
Magnus T. Jensen ◽  
Nay Aung ◽  
Jackie Cooper ◽  
Karim Lekadir ◽  
...  
Keyword(s):  
Heart Failure ◽  
Cox Regression ◽  
Cardiac Risk ◽  
Uk Biobank ◽  
Contributing Factors ◽  
Increased Risk ◽  
Study Population ◽  
The Uk

Aims: To investigate the effect of diabetes on mortality and incident heart failure (HF) according to sex, in the low risk population of UK Biobank. To evaluate potential contributing factors for any differences seen in HF end-point.Methods: The entire UK Biobank study population were included. Participants that withdrew consent or were diagnosed with diabetes after enrolment were excluded from the study. Univariate and multivariate cox regression models were used to assess endpoints of mortality and incident HF, with median follow-up periods of 9 years and 8 years respectively.Results: A total of 493,167 participants were included, hereof 22,685 with diabetes (4.6%). Two thousand four hundred fifty four died and 1,223 were diagnosed or admitted with HF during the follow up periods of 9 and 8 years respectively. Overall, the mortality and HF risk were almost doubled in those with diabetes compared to those without diabetes (hazard ratio (HR) of 1.9 for both mortality and heart failure) in the UK Biobank population. Women with diabetes (both types) experience a 22% increased risk of HF compared to men (HR of 2.2 (95% CI: 1.9–2.5) vs. 1.8 (1.7–2.0) respectively). Women with type 1 diabetes (T1DM) were associated with 88% increased risk of HF compared to men (HR 4.7 (3.6–6.2) vs. 2.5 (2.0–3.0) respectively), while the risk of HF for type 2 diabetes (T2DM) was 17% higher in women compared to men (2.0 (1.7–2.3) vs. 1.7 (1.6–1.9) respectively). The increased risk of HF in women was independent of confounding factors. The findings were similar in a model with all-cause mortality as a competing risk. This interaction between sex, diabetes and outcome of HF is much more prominent for T1DM (p = 0.0001) than T2DM (p = 0.1).Conclusion: Women with diabetes, particularly those with T1DM, experience a greater increase in risk of heart failure compared to men with diabetes, which cannot be explained by the increased prevalence of cardiac risk factors in this cohort.

scholarly journals Influence of blood pressure on pneumonia risk: Epidemiological association and Mendelian randomisation in the UK Biobank

2020 ◽  
Author(s):  
Seyedeh M. Zekavat ◽  
Michael Honigberg ◽  
James Pirruccello ◽  
Puja Kohli ◽  
Elizabeth W. Karlson ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Observational Studies ◽  
Mendelian Randomisation ◽  
List Type ◽  
Uk Biobank ◽  
Increased Risk ◽  
Reduce Risk ◽  
Novel Coronavirus ◽  
The Uk

AbstractObjectivesTo determine whether elevated blood pressure influences risk for respiratory infection.DesignProspective, population-based epidemiological and Mendelian randomisation studies.SettingUK Biobank.Participants377,143 self-identified British descent (54% women; median age 58 years) participants in the UK Biobank.Main outcome measuresFirst incident pneumonia over an average of 8 follow-up years.Results107,310 (30%) participants had hypertension at UK Biobank enrolment, and 9,969 (3%) developed a pneumonia during follow-up. Prevalent hypertension at baseline was significantly associated with increased risk for incident respiratory disease including pneumonia (hazard ratio 1.36 (95% confidence interval 1.29 to 1.43), P<0.001), acute respiratory distress syndrome or respiratory failure (1.43 (1.29 to 1.59), P<0.001), and chronic lower respiratory disease (1.30 (1.25 to 1.36), P<0.001), independent of age, age2, sex, smoking status, BMI, prevalent diabetes mellitus, prevalent coronary artery disease, and principal components of ancestry. Mendelian randomisation analyses indicated that genetic predisposition to a 5 mmHg increase in blood pressure was associated with increased risk of incident pneumonia for SBP (1.08, (1.04 to 1.13), P<0.001) and DBP (1.11 (1.03 to 1.20), P=0.005). Additionally, consistent with epidemiologic associations, increase in blood pressure genetic risk was significantly associated with reduced forced expiratory volume in the first second, forced vital capacity, and the ratio of the two (P<0.001 for all).ConclusionsThese results strongly suggest that elevated blood pressure independently increases risk for pneumonia and reduces pulmonary function. Maintaining adequate blood pressure control, in addition to other measures, may reduce risk for pneumonia. Whether the present findings are generalizable to novel coronavirus disease 2019 (COVID-19) require further study.Summary BoxSection 1: What is already known on this topicHypertension has been associated with pneumonia in small observational studies.Based on early epidemiologic analyses, hypertension is described as a risk factor for SARS-CoV-2 infection and associated novel coronavirus disease 2019 (COVID-19).The influence of hypertension on pneumonia risk is difficult to assess in traditional observational studies.Section 2: What this study addsOur pre-COVID-19 analyses are consistent with a causal relationship between increased blood pressure and increased risk for incident respiratory infections, as well as between increased blood pressure and reduced pulmonary function.These results support hypertension as a pneumonia risk factor; efforts to optimize blood pressure may reduce risk for pneumonia.

Monoclonal Gammopathy of Undetermined Significance and Risk of Infections: A Population-Based Study

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 4053-4053
Author(s):  
Sigurdur Y. Kristinsson ◽  
Tang Min ◽  
Ruth Pfeiffer ◽  
Magnus Björkholm ◽  
Lynn Goldin ◽  
...  
Keyword(s):  
Monoclonal Gammopathy ◽  
Bacterial Infections ◽  
Viral Infections ◽  
Population Based ◽  
M Protein ◽  
Risk Of Death ◽  
Prophylactic Measures ◽  
Increased Risk ◽  
Undetermined Significance

Abstract Abstract 4053 Background: Based on clinical case reports and small hospital-based patient series, monoclonal gammopathy of undetermined significance (MGUS) has been reported to increase morbidity due to bacterial infections; however, no comprehensive evaluation has been conducted. Patients and methods: Using population-based data from Sweden, we assessed the risks of viral and bacterial infections (reported to the Patient-Registry) in 5,326 MGUS patients diagnosed 1958–2006, compared to 20,161 matched population-based controls. We fit Cox proportional hazard models to estimate hazard ratios (HRs) as measures of risk. Results: At 5 years of follow-up MGUS patients had a 2.1-fold (95% confidence interval (CI) 2.1–2.3) increased risk of developing any infection compared to controls; at 10 years of follow-up, the risk was very similar (HR=2.2; 95% CI 2.0–2.3). MGUS patients had a 2.2-fold (95% CI 2.0–2.4) and 2.1-fold (95% CI 2.0–2.3) increased risk of developing bacterial infections at 5 and 10 years, respectively. A significantly increased risk (P<0.05) was found for pneumonia, osteomyelitis, septicemia, pyelonephritis, cellulitis, endocarditis and meningitis. We also assessed the risk of developing viral infections; compared to controls, MGUS patients had a 2.7-fold (95% CI 2.2–3.3) and 2.9-fold (95% CI 2.3–3.7) increased risk at 5 and 10 years, respectively, with a significantly increased risk for influenza and herpes infections (P<0.05). Risk of infections did not differ by MGUS isotype. MGUS patients with an M-protein >2.5 g/dL at diagnosis had higher risks of infections compared to those <0.5 g/dL. However, compared to controls the risk of infections was also significantly increased among MGUS patients with a concentration <0.5 g/dL. MGUS patients with (versus without) infections had no excess risk of developing multiple myeloma or related malignancies. Summary and Conclusions: Based on over 5,000 MGUS patients, we found a 2-fold higher risk of developing bacterial and viral infections, compared to controls. The risk was highest among MGUS patients with high M-protein concentrations at diagnosis (>2.5 g/dL); however, the risk was still significantly increased among those with a concentration <0.5 g/dL. Infections in patients with MGUS were not associated with an increased risk of malignant transformation. We recently showed that patients with MGUS have a 3-fold risk of death in bacterial infections. Our findings may have clinical implications for treatment strategies and prophylactic measures, as well as surveillance of MGUS patients. Disclosures: No relevant conflicts of interest to declare.

scholarly journals Hemochromatosis Mutations, Brain Iron Imaging, and Dementia in the UK Biobank Cohort

2021 ◽  
pp. 1-9
Author(s):  
Janice L. Atkins ◽  
Luke C. Pilling ◽  
Christine J. Heales ◽  
Sharon Savage ◽  
Chia-Ling Kuo ◽  
...  
Keyword(s):  
Iron Reduction ◽  
Brain Mri ◽  
European Ancestry ◽  
Uk Biobank ◽  
Brain Iron ◽  
Mri Features ◽  
Incident Dementia ◽  
Hfe Mutations ◽  
The Uk

Background: Brain iron deposition occurs in dementia. In European ancestry populations, the HFE p.C282Y variant can cause iron overload and hemochromatosis, mostly in homozygous males. Objective: To estimated p.C282Y associations with brain MRI features plus incident dementia diagnoses during follow-up in a large community cohort. Methods: UK Biobank participants with follow-up hospitalization records (mean 10.5 years). MRI in 206 p.C282Y homozygotes versus 23,349 without variants, including T2 * measures (lower values indicating more iron). Results: European ancestry participants included 2,890 p.C282Y homozygotes. Male p.C282Y homozygotes had lower T2 * measures in areas including the putamen, thalamus, and hippocampus, compared to no HFE mutations. Incident dementia was more common in p.C282Y homozygous men (Hazard Ratio HR = 1.83; 95% CI 1.23 to 2.72, p = 0.003), as was delirium. There were no associations in homozygote women or in heterozygotes. Conclusion: Studies are needed of whether early iron reduction prevents or slows related brain pathologies in male HFE p.C282Y homozygotes.

scholarly journals Socioeconomic Inequalities and Ethnicity Are Associated with a Positive COVID-19 Test among Cancer Patients in the UK Biobank Cohort

Cancers ◽  
2021 ◽  
Vol 13 (7) ◽  
pp. 1514
Author(s):  
Shing Fung Lee ◽  
Maja Nikšić ◽  
Bernard Rachet ◽  
Maria-Jose Sanchez ◽  
Miguel Angel Luque-Fernandez
Keyword(s):  
Cancer Patients ◽  
Socioeconomic Inequalities ◽  
Uk Biobank ◽  
Incident Cancer ◽  
Increased Risk ◽  
Exposure Variable ◽  
Independent Risk Factors ◽  
The Uk ◽  
Deprived Areas

We explored the role of socioeconomic inequalities in COVID-19 incidence among cancer patients during the first wave of the pandemic. We conducted a case-control study within the UK Biobank cohort linked to the COVID-19 tests results available from 16 March 2020 until 23 August 2020. The main exposure variable was socioeconomic status, assessed using the Townsend Deprivation Index. Among 18,917 participants with an incident malignancy in the UK Biobank cohort, 89 tested positive for COVID-19. The overall COVID-19 incidence was 4.7 cases per 1000 incident cancer patients (95%CI 3.8–5.8). Compared with the least deprived cancer patients, those living in the most deprived areas had an almost three times higher risk of testing positive (RR 2.6, 95%CI 1.1–5.8). Other independent risk factors were ethnic minority background, obesity, unemployment, smoking, and being diagnosed with a haematological cancer for less than five years. A consistent pattern of socioeconomic inequalities in COVID-19 among incident cancer patients in the UK highlights the need to prioritise the cancer patients living in the most deprived areas in vaccination planning. This socio-demographic profiling of vulnerable cancer patients at increased risk of infection can inform prevention strategies and policy improvements for the coming pandemic waves.

scholarly journals Impact of atrial fibrillation pattern on outcomes after left atrial appendage closure: lessons from the prospective LAARGE registry

2021 ◽  
Author(s):  
Shinwan Kany ◽  
Johannes Brachmann ◽  
Thorsten Lewalter ◽  
Ibrahim Akin ◽  
Horst Sievert ◽  
...  
Keyword(s):  
Atrial Fibrillation ◽  
Left Atrial Appendage ◽  
Systemic Embolism ◽  
Long Term Outcomes ◽  
Increased Risk ◽  
History Of ◽  
One Year ◽  
The One

Abstract Background Non-paroxysmal (NPAF) forms of atrial fibrillation (AF) have been reported to be associated with an increased risk for systemic embolism or death. Methods Comparison of procedural details and long-term outcomes in patients (pts) with paroxysmal AF (PAF) against controls with NPAF in the prospective, multicentre observational registry of patients undergoing LAAC (LAARGE). Results A total of 638 pts (PAF 274 pts, NPAF 364 pts) were enrolled. In both groups, a history of PVI was rare (4.0% vs 1.6%, p = 0.066). The total CHA2DS2-VASc score was lower in the PAF group (4.4 ± 1.5 vs 4.6 ± 1.5, p = 0.033), while HAS-BLED score (3.8 ± 1.1 vs 3.9 ± 1.1, p = 0.40) was comparable. The rate of successful implantation was equally high (97.4% vs 97.8%, p = 0.77). In the three-month echo follow-up, LA thrombi (2.1% vs 7.3%, p = 0.12) and peridevice leak > 5 mm (0.0% vs 7.1%, p = 0.53) were numerically higher in the NPAF group. Overall, in-hospital complications occurred in 15.0% of the PAF cohort and 10.7% of the NPAF cohort (p = 0.12). In the one-year follow-up, unadjusted mortality (8.4% vs 14.0%, p = 0.039) and combined outcome of death, stroke and systemic embolism (8.8% vs 15.1%, p = 0.022) were significantly higher in the NPAF cohort. After adjusting for CHA2DS2-VASc and previous bleeding, NPAF was associated with increased death/stroke/systemic embolism (HR 1.67, 95% CI 1.02–2.72, p = 0.041). Conclusion Atrial fibrillation type did not impair periprocedural safety or in-hospital MACE patients undergoing LAAC. However, after one year, NPAF was associated with higher mortality. Graphic abstract

scholarly journals Cumulative incidence and risk factors for radiation induced leukoencephalopathy in high grade glioma long term survivors

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Robert Terziev ◽  
Dimitri Psimaras ◽  
Yannick Marie ◽  
Loic Feuvret ◽  
Giulia Berzero ◽  
...  
Keyword(s):  
Risk Factors ◽  
Cumulative Incidence ◽  
High Grade Glioma ◽  
High Grade ◽  
Nucleotide Polymorphisms ◽  
Increased Risk ◽  
Radiation Induced ◽  
Long Term Survivors

AbstractThe incidence and risk factors associated with radiation-induced leukoencephalopathy (RIL) in long-term survivors of high-grade glioma (HGG) are still poorly investigated. We performed a retrospective research in our institutional database for patients with supratentorial HGG treated with focal radiotherapy, having a progression-free overall survival > 30 months and available germline DNA. We reviewed MRI scans for signs of leukoencephalopathy on T2/FLAIR sequences, and medical records for information on cerebrovascular risk factors and neurological symptoms. We investigated a panel of candidate single nucleotide polymorphisms (SNPs) to assess genetic risk. Eighty-one HGG patients (18 grade IV and 63 grade III, 50M/31F) were included in the study. The median age at the time of radiotherapy was 48 years old (range 18–69). The median follow-up after the completion of radiotherapy was 79 months. A total of 44 patients (44/81, 54.3%) developed RIL during follow-up. Twenty-nine of the 44 patients developed consistent symptoms such as subcortical dementia (n = 28), gait disturbances (n = 12), and urinary incontinence (n = 9). The cumulative incidence of RIL was 21% at 12 months, 42% at 36 months, and 48% at 60 months. Age > 60 years, smoking, and the germline SNP rs2120825 (PPARg locus) were associated with an increased risk of RIL. Our study identified potential risk factors for the development of RIL (age, smoking, and the germline SNP rs2120825) and established the rationale for testing PPARg agonists in the prevention and management of late-delayed radiation-induced neurotoxicity.

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