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Knowledge about a patient's physical fitness can aid in medical decision-making, but objective assessment can be challenging and time-consuming. We aimed to investigate the concordance of self-reported health status and physical functioning with the 6 minute walking distance (6MWD) as objective measure of physical performance. The prospective characteristics and course of heart failure stages A/B and determinants of progression (STAAB) cohort study iteratively follows a representative sample of residents of the city of Würzburg, Germany, aged 30-79 years, without a history of heart failure (HF). The 6MWD was measured in 2752 individuals (aged 58 ± 11 years, 51% women) from a population-based cohort under strictly standardized conditions. Self-reported health status and physical functioning were assessed from items of the short form 36 (SF-36). After the respective classification of self-reported health status and physical functioning into 'good', 'moderate', and 'poor', we determined the association of these categories with 6MWD by applying a generalized linear model adjusted for age and sex. Prevalence of self-reported good/moderate/poor general health and physical functioning was 41/52/7% and 45/48/7%, respectively. Mean 6MWD in the respective categories was 574 ± 70/534 ± 76/510 ± 87 m, and 574 ± 72/534 ± 73/490 ± 82 m, with significant sex-specific differences between all categories (all p < 0.001) as well as significant differences between the respective groups except for the categories 'moderate' and 'poor' health status in men. This cross-sectional analysis revealed a strong association between self-reported health status and physical functioning with the objective assessment of 6MWD, suggesting that physicians can rely on their patients' respective answers. Nevertheless, sex-specific perception and attribution of general health and physical functioning deserve further in-depth investigation. Decision-making based on self-reported health requires prospective evaluation in population-based cohorts as well as adult inpatients.
Subject(s)
Health Status , Self Report , Humans , Middle Aged , Female , Male , Aged , Adult , Germany/epidemiology , Prospective Studies , Physical Fitness , Heart Failure/epidemiology , Heart Failure/physiopathology , Walk TestABSTRACT
The medical burden of stroke extends beyond the brain injury itself and is largely determined by chronic comorbidities that develop secondarily. We hypothesized that these comorbidities might share a common immunological cause, yet chronic effects post-stroke on systemic immunity are underexplored. Here, we identify myeloid innate immune memory as a cause of remote organ dysfunction after stroke. Single-cell sequencing revealed persistent pro-inflammatory changes in monocytes/macrophages in multiple organs up to 3 months after brain injury, notably in the heart, leading to cardiac fibrosis and dysfunction in both mice and stroke patients. IL-1ß was identified as a key driver of epigenetic changes in innate immune memory. These changes could be transplanted to naive mice, inducing cardiac dysfunction. By neutralizing post-stroke IL-1ß or blocking pro-inflammatory monocyte trafficking with a CCR2/5 inhibitor, we prevented post-stroke cardiac dysfunction. Such immune-targeted therapies could potentially prevent various IL-1ß-mediated comorbidities, offering a framework for secondary prevention immunotherapy.
Subject(s)
Brain Injuries , Immunity, Innate , Immunologic Memory , Inflammation , Interleukin-1beta , Mice, Inbred C57BL , Monocytes , Animals , Mice , Interleukin-1beta/metabolism , Brain Injuries/immunology , Humans , Male , Monocytes/metabolism , Monocytes/immunology , Inflammation/immunology , Macrophages/immunology , Macrophages/metabolism , Stroke/complications , Stroke/immunology , Heart Diseases/immunology , Female , Receptors, CCR2/metabolism , Fibrosis , Epigenesis, Genetic , Trained ImmunityABSTRACT
BACKGROUND: The incidental finding of a pericardial effusion (PE) poses a challenge in clinical care. PE is associated with malignant conditions or severe cardiac disease but may also be observed in healthy individuals. This study explored the prevalence, determinants, course, and prognostic relevance of PE in a population-based cohort. METHODS AND RESULTS: The STAAB (Characteristics and Course of Heart Failure Stages A/B and Determinants of Progression) cohort study recruited a representative sample of the population of Würzburg, aged 30 to 79 years. Participants underwent quality-controlled transthoracic echocardiography including the dedicated evaluation of the pericardial space. Of 4965 individuals included at baseline (mean age, 55±12 years; 52% women), 134 (2.7%) exhibited an incidentally diagnosed PE (median diameter, 2.7 mm; quartiles, 2.0-4.1 mm). In multivariable logistic regression, lower body mass index and higher NT-proBNP (N-terminal pro-B-type natriuretic peptide) levels were associated with PE at baseline, whereas inflammation, malignancy, and rheumatoid disease were not. Among the 3901 participants attending the follow-up examination after a median time of 34 (30-41) months, PE was found in 60 individuals (1.5%; n=18 new PE, n=42 persistent PE). Within the follow-up period, 37 participants died and 93 participants reported a newly diagnosed malignancy. The presence of PE did not predict all-cause death or the development of new malignancy. CONCLUSIONS: Incidental PE was detected in about 3% of individuals, with the vast majority measuring <10 mm and completely resolving. PE was not associated with inflammation markers, death, incident heart failure, or malignancy. Our findings corroborate the view of current guidelines that a small PE in asymptomatic individuals can be considered an innocent phenomenon and does not require extensive short-term monitoring.
Subject(s)
Echocardiography , Incidental Findings , Peptide Fragments , Pericardial Effusion , Humans , Female , Middle Aged , Male , Pericardial Effusion/epidemiology , Pericardial Effusion/diagnostic imaging , Pericardial Effusion/mortality , Aged , Adult , Prognosis , Prevalence , Peptide Fragments/blood , Natriuretic Peptide, Brain/blood , Risk Factors , Biomarkers/blood , Heart Failure/epidemiology , Heart Failure/mortality , Heart Failure/diagnosis , Predictive Value of Tests , Disease Progression , Time FactorsABSTRACT
BACKGROUND: Compared to workers of larger companies it is less clear what health promoting interventions might be beneficial for employees of small businesses and self-employed individuals. OBJECTIVE: Our aim was to critically appraise trials investigating health promotion programs among small business workers and self-employed individuals, by means of a systematic review. METHODS: We conducted a search of primary studies using MEDLINE, Web of Science, LIVIVO and the Cochrane library. Our assessment followed the recommendations of the Cochrane Handbook for Systematic Reviews of Interventions and PRISMA. RESULTS: We identified six trials including 5,854 participants from Asia, North America and Australia. Most were of moderate methodological quality, only one was of low quality. Some of the supervised psycho-educational lifestyle programs focusing on individual behavior changes showed benefits in terms of stress reduction and increased physical activity levels among small enterprise employees. CONCLUSIONS: There is a huge knowledge gap on evidence-based health promotion interventions for self-employed and for small business workers, especially in Europe.
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BACKGROUND AND AIMS: Acute ischemic stroke (AIS) outcome prognostication remains challenging despite available prognostic models. We investigated whether a biomarker panel improves the predictive performance of established prognostic scores. METHODS: We investigated the improvement in discrimination, calibration, and overall performance by adding five biomarkers (procalcitonin, copeptin, cortisol, mid-regional pro-atrial natriuretic peptide (MR-proANP), and N-terminal pro-B-type natriuretic peptide (NT-proBNP)) to the Acute Stroke Registry and Analysis of Lausanne (ASTRAL) and age/NIHSS scores using data from two prospective cohort studies (SICFAIL, PREDICT) and one clinical trial (STRAWINSKI). Poor outcome was defined as mRS > 2 at 12 (SICFAIL, derivation dataset) or 3 months (PREDICT/STRAWINSKI, pooled external validation dataset). RESULTS: Among 412 SICFAIL participants (median age 70 years, quartiles 59-78; 63% male; median NIHSS score 3, quartiles 1-5), 29% had a poor outcome. Area under the curve of the ASTRAL and age/NIHSS were 0.76 (95% CI 0.71-0.81) and 0.77 (95% CI 0.73-0.82), respectively. Copeptin (0.79, 95% CI 0.74-0.84), NT-proBNP (0.80, 95% CI 0.76-0.84), and MR-proANP (0.79, 95% CI 0.75-0.84) significantly improved ASTRAL score's discrimination, calibration, and overall performance. Copeptin improved age/NIHSS model's discrimination, copeptin, MR-proANP, and NT-proBNP improved its calibration and overall performance. In the validation dataset (450 patients, median age 73 years, quartiles 66-81; 54% men; median NIHSS score 8, quartiles 3-14), copeptin was independently associated with various definitions of poor outcome and also mortality. Copeptin did not increase model's discrimination but it did improve calibration and overall model performance. DISCUSSION: Copeptin, NT-proBNP, and MR-proANP improved modest but consistently the predictive performance of established prognostic scores in patients with mild AIS. Copeptin was most consistently associated with poor outcome in patients with moderate to severe AIS, although its added prognostic value was less obvious.
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Heart failure (HF) is associated with poor outcome after stroke, but data from large prospective trials are sparse.We assessed the impact of HF on clinical endpoints in patients hospitalized with acute ischemic stroke or transient ischemic attack (TIA) enrolled in the prospective, multicenter Systematic Monitoring for Detection of Atrial Fibrillation in Patients with Acute Ischemic Stroke (MonDAFIS) trial. HF was defined as left ventricular ejection fraction (LVEF) < 55% or a history of HF on admission. The composite of recurrent stroke, major bleeding, myocardial infarction, and all-cause death, and its components during the subsequent 24 months were assessed. We used estimated hazard ratios in confounder-adjusted models. Overall, 410/2562 (16.0%) stroke patients fulfilled the HF criteria (i.e. 381 [14.9%] with LVEF < 55% and 29 [1.9%] based on medical history). Patients with HF had more often diabetes, coronary and peripheral arterial disease and presented with more severe strokes on admission. HF at baseline correlated with myocardial infarction (HR 2.21; 95% CI 1.02-4.79), and all-cause death (HR 1.67; 95% CI 1.12-2.50), but not with major bleed (HR 1.93; 95% CI 0.73-5.06) or recurrent stroke/TIA (HR 1.08; 95% CI 0.75-1.57). The data were adjusted for age, stroke severity, cardiovascular risk factors, and randomization. Patients with ischemic stroke or TIA and comorbid HF have a higher risk of myocardial infarction and death compared with non-HF patients whereas the risk of recurrent stroke or major hemorrhage was similar. Trial registration number Clinicaltrials.gov NCT02204267.
Subject(s)
Heart Failure , Ischemic Stroke , Humans , Male , Female , Aged , Heart Failure/mortality , Heart Failure/complications , Heart Failure/physiopathology , Prospective Studies , Ischemic Stroke/mortality , Ischemic Stroke/complications , Middle Aged , Risk Factors , Recurrence , Aged, 80 and overABSTRACT
INTRODUCTION: Blood-based biomarkers may improve prediction of functional outcome in patients with acute ischemic stroke. The role of neurofilament light chain (NfL) and glial fibrillary acidic (GFAP) as potential biomarkers especially in severe stroke patients is unknown. PATIENTS AND METHODS: Prospective, monocenter, cohort study including consecutive patients with severe ischemic stroke in the anterior circulation on admission (NIHSS score ⩾ 6 points or indication for mechanical thrombectomy). Outcome was assessed 3 months after the index stroke by the modified Rankin Scale (mRS). Serum biomarkers levels of NfL and GFAP were determined by ultrasensitive ELISA. Univariate and multivariate logistic regression models were performed to determine the association of biomarker levels and functional disability. Discrimination, calibration, and overall performance were analyzed in different models via AUROC, calibration plots (with Emax and Eavg), Brier-score and R2 using variables, identified as important covariates for functional outcome in previous studies. RESULTS: Between 06/2020 and 08/2021, 213 patients were included [47% female, mean age 76 (SD ± 12) years, median NIHSS score 13 (interquartile range, IQR 9; 17)]. Biomarker serum levels were measured at a median of 1 [IQR, 1; 2] day after admission. Compared to patients with mRS 0-2 at 3 months, patients with mRS 3-6 had higher serum levels of NfL (median: 136 pg/ml vs 41 pg/ml; p < 0.0001) and GFAP (700 ng/ml vs 9.6 ng/ml; p < 0.0001). Both biomarkers were significantly associated with functional outcome [adjusted logistic regression, odds ratio (95% CI) for NfL: 2.63 (1.62; 4.56), GFAP: 2.16 (1.58; 3.09)]. In all models the addition of serum NfL led to a significant improvement in the AUROC, as did the addition of serum GFAP. Calibration plots showed high agreement between the predicted and observed outcomes and after addition of the two blood-based biomarkers there was an improvement of the overall performance. CONCLUSION: Prediction of functional outcome after severe acute ischemic stroke was improved by the blood-based biomarkers serum NfL and GFAP, measured in the acute phase of stroke. These findings have to be replicated in independent external cohorts.Study registration: DRKS00022064.
Subject(s)
Biomarkers , Glial Fibrillary Acidic Protein , Ischemic Stroke , Neurofilament Proteins , Humans , Glial Fibrillary Acidic Protein/blood , Female , Male , Neurofilament Proteins/blood , Biomarkers/blood , Aged , Ischemic Stroke/blood , Ischemic Stroke/diagnosis , Ischemic Stroke/therapy , Prospective Studies , Aged, 80 and over , Middle Aged , Prognosis , Severity of Illness IndexABSTRACT
Background: Despite the high prevalence and major disability associated with fatigue and cognitive deficits after SARS-CoV-2 infection, little is known about long-term trajectories of these sequelae. We aimed to assess long-term trajectories of these conditions and to identify risk factors for non-recovery. Methods: We analyzed longitudinal data from the population-based COVIDOM/NAPKON-POP cohort in Germany. Participants with confirmed SARS-CoV-2 infection were assessed at least 6 months (baseline) and again at least 18 months (follow-up) after infection using the Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-Fatigue) Scale (cutoff ≤ 30) and the Montreal Cognitive Assessment (MoCA, cutoff ≤ 25). Predictors of recovery from fatigue or cognitive deficits between assessments were identified through univariate and multivariable logistic regression models. The COVIDOM study is registered at the German registry for clinical studies (DRKS00023742) and at ClinicalTrials.gov (NCT04679584). Findings: Between 15 November 2020 and 9 May 2023, a total of 3038 participants were assessed at baseline (median 9 months after infection) and 83% responded to invitations for follow-up (median 26 months after infection). At baseline, 21% (95% confidence interval (CI) [20%, 23%]) had fatigue and 23% (95% CI [22%, 25%]) had cognitive deficits according to cutoff scores on the FACIT-Fatigue or MoCA. Participants with clinically relevant fatigue (at baseline) showed significant improvement in fatigue scores at follow-up (Hedges' g [95% CI] = 0.73 [0.60, 0.87]) and 46% (95% CI [41%, 50%]) had recovered from fatigue. Participants with cognitive deficits showed a significant improvement in cognitive scores (g [95% CI] = 1.12 [0.90, 1.33]) and 57% (95% CI [50%, 64%]) had recovered from cognitive deficits. Patients with fatigue exhibiting a higher depressive symptom burden and/or headache at baseline were significantly less likely to recover. Significant risk factors for cognitive non-recovery were male sex, older age and <12 years of school education. Importantly, SARS-CoV-2 reinfection had no significant impact on recovery from fatigue or cognitive deficits. Interpretation: Fatigue and cognitive deficits are common sequelae after SARS-CoV-2 infection. These syndromes improved over time and about half of the patients recovered within two years. The identified risk factors for non-recovery from fatigue and cognitive deficits could play an important role in shaping targeted strategies for treatment and prevention. Funding: Funded by the German Federal Ministry of Education and Research (BMBF; grant number 01KX2121) and German Research Foundation (DFG) Excellence Cluster "Position Medicine in Information".
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BACKGROUND: Depression and fatigue are commonly observed sequelae following viral diseases such as COVID-19. Identifying symptom constellations that differentially classify post-COVID depression and fatigue may be helpful to individualize treatment strategies. Here, we investigated whether self-reported post-COVID depression and post-COVID fatigue are associated with the same or different symptom constellations. METHODS: To address this question, we used data from COVIDOM, a population-based cohort study conducted as part of the NAPKON-POP platform. Data were collected in three different German regions (Kiel, Berlin, Würzburg). We analyzed data from >2000 individuals at least six months past a PCR-confirmed COVID-19 disease, using elastic net regression and cluster analysis. The regression model was developed in the Kiel data set, and externally validated using data sets from Berlin and Würzburg. RESULTS: Our results revealed that post-COVID depression and fatigue are associated with overlapping symptom constellations consisting of difficulties with daily activities, perceived health-related quality of life, chronic exhaustion, unrestful sleep, and impaired concentration. Confirming the overlap in symptom constellations, a follow-up cluster analysis could categorize individuals as scoring high or low on depression and fatigue but could not differentiate between both dimensions. LIMITATIONS: The data presented are cross-sectional, consisting primarily of self-reported questionnaire or medical records rather than biometric data. CONCLUSIONS: In summary, our results suggest a strong link between post-COVID depression and fatigue, highlighting the need for integrative treatment approaches.
Subject(s)
COVID-19 , Sleep Wake Disorders , Humans , Quality of Life , Depression/epidemiology , Depression/therapy , Cross-Sectional Studies , Prospective Studies , Cohort Studies , COVID-19/complications , COVID-19/epidemiology , Sleep Wake Disorders/epidemiology , Sleep Wake Disorders/etiology , Sleep Wake Disorders/therapy , Fatigue/epidemiology , Fatigue/etiologyABSTRACT
Aims: Machine-learning (ML)-based automated measurement of echocardiography images emerges as an option to reduce observer variability. The objective of the study is to improve the accuracy of a pre-existing automated reading tool ('original detector') by federated ML-based re-training. Methods and results: Automatisierte Vermessung der Echokardiographie was based on the echocardiography images of n = 4965 participants of the population-based Characteristics and Course of Heart Failure Stages A-B and Determinants of Progression Cohort Study. We implemented federated ML: echocardiography images were read by the Academic Core Lab Ultrasound-based Cardiovascular Imaging at the University Hospital Würzburg (UKW). A random algorithm selected 3226 participants for re-training of the original detector. According to data protection rules, the generation of ground truth and ML training cycles took place within the UKW network. Only non-personal training weights were exchanged with the external cooperation partner for the refinement of ML algorithms. Both the original detectors as the re-trained detector were then applied to the echocardiograms of n = 563 participants not used for training. With regard to the human referent, the re-trained detector revealed (i) superior accuracy when contrasted with the original detector's performance as it arrived at significantly smaller mean differences in all but one parameter, and a (ii) smaller absolute difference between measurements when compared with a group of different human observers. Conclusion: Population data-based ML in a federated ML set-up was feasible. The re-trained detector exhibited a much lower measurement variability than human readers. This gain in accuracy and precision strengthens the confidence in automated echocardiographic readings, which carries large potential for applications in various settings.
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AIMS: The 6-min walk test is an inexpensive, safe, and easy tool to assess functional capacity in patients with cardiopulmonary diseases including heart failure (HF). There is a lack of reference values, which are a prerequisite for the interpretation of test results in patients. Furthermore, determinants independent of the respective disease need to be considered when interpreting the 6-min walk distance (6MWD). METHODS: The prospective Characteristics and Course of Heart Failure Stages A-B and Determinants of Progression (STAAB) cohort study investigates a representative sample of residents of the City of Würzburg, Germany, aged 30 to 79 years, without a history of HF. Participants underwent detailed clinical and echocardiographic phenotyping as well as a standardized assessment of the 6MWD using a 15-m hallway. RESULTS: In a sample of 2762 participants (51% women, mean age 58 ± 11 years), we identified age and height, but not sex, as determinants of the 6MWD. While a worse metabolic profile showed a negative association with the 6MWD, a better systolic and diastolic function showed a positive association with 6MWD. From a subgroup of 681 individuals without any cardiovascular risk factors (60% women, mean age 52 ± 10 years), we computed age- and height-specific reference percentiles. CONCLUSION: In a representative sample of the general population free from HF, we identified determinants of the 6MWD implying objective physical fitness associated with metabolic health as well as with cardiac structure and function. Furthermore, we derived reference percentiles applicable when using a 15-m hallway.
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BACKGROUND: After infection with SARS-CoV-2 a relevant proportion of patients complains about persisting symptoms, a condition termed Post-COVID-19-syndrome (PC19S). So far, possible treatments are under investigation. Among others, neurotropic vitamins and anti-inflammatory substances are potential options. Thus, the PreVitaCOV trial aims to assess feasibility, safety, and effectiveness of treating patients in primary care with prednisolone and/or vitamin B1, B6 and B12. METHODS: The phase IIIb, multi-centre randomised, double-blind, and placebo-controlled PreVitaCOV trial has a factorial design and is planned as a two-phase approach. The pilot phase assessed feasibility and safety and was transformed into a confirmatory phase to evaluate effectiveness since feasibility was proven. Adult patients with PC19S after a documented SARS-CoV-2 infection at least 12 weeks ago are randomly assigned to 4 parallel treatments: prednisolone 20 mg for five days followed by 5 mg for 23 days (trial drug 1), B vitamins (B1 (100 mg OD), B6 (50 mg OD), and B12 (500 µg OD)) for 28 days (trial drug 2), trial drugs 1 and 2, or placebo. The primary outcome of the pilot phase was defined as the retention rate of the first 100 patients. Values of ≥ 85% were considered as confirmation of feasibility, this criterion was even surpassed by a retention rate of 98%. After transformation, the confirmatory phase proceeds by enrolling 240 additional patients. The primary outcome for the study is the change of symptom severity from baseline to day 28 as assessed by a tailored Patient Reported Outcomes Measurement Information System (PROMIS) total score referring to five symptom domains known to be typical for PC19S (fatigue, dyspnoea, cognition, anxiety, depression). The confirmatory trial is considered positive if superiority of any treatment is demonstrated over placebo operationalised by an improvement of at least 3 points on the PROMIS total score (t-score). DISCUSSION: The PreVitaCOV trial may contribute to the understanding of therapeutic approaches in PC19S in a primary care context. TRIAL REGISTRATION: EudraCT: 2022-001041-20. DRKS: DRKS00029617. CLINICALTRIALS: gov: F001AM02222_1 (registered: 05 Dec 2022).
Subject(s)
COVID-19 , Thiamine , Adult , Humans , Prednisolone/therapeutic use , Feasibility Studies , SARS-CoV-2 , Vitamins , Double-Blind Method , Syndrome , Primary Health Care , Randomized Controlled Trials as Topic , Multicenter Studies as Topic , Clinical Trials, Phase III as TopicABSTRACT
BACKGROUND AND PURPOSE: C-reactive protein serves as a marker of inflammation and is linked to depression in the general population. We aimed to assess whether elevated baseline levels of high-sensitivity C-reactive protein (hs-CRP) are associated with depressive symptoms over time in a prospective cohort of mild-to-moderate first-ever ischemic stroke patients. METHODS: Data were obtained from the Prospective Cohort with Incident Stroke Berlin (NCT01363856). Depressive symptoms were assessed with the Center for Epidemiologic Studies Depression Scale (CES-D) at three annual follow-up points. We assessed the association of elevated levels of hs-CRP with CES-D scores over time via linear mixed models. In a subgroup analysis, we explored an interaction effect with sex. RESULTS: We included 585 ischemic stroke patients with baseline data on CRP levels. The mean age was 67 (13 SD), 39% (n = 226) were female, and the median National Institutes of Health Stroke Scale (NIHSS) was 3 (IQR 1-4). Twenty percent of survivors showed evidence for depressive symptoms one year after stroke with CES-D ≥ 16, 21% at year two, and 17% at year three. Higher log-transformed baseline hs-CRP levels were associated with higher CES-D Scores over time in the adjusted linear mixed model (ß = 1.28; (95% CI 0.22-2.34)). The subgroup analysis revealed an interaction effect of hs-CRP on depressive symptoms in women (ß = 2.33; (95% CI 0.71-3.95)). CONCLUSION: In our cohort with mild-to-moderate first-ever ischemic stroke patients, hs-CRP levels were associated with more depressive symptoms over time, with an interaction effect for the female sex. STUDY REGISTRATION: https://clinicaltrials.gov ; Unique identifier: NCT01363856.
Subject(s)
Ischemic Stroke , Stroke , Aged , Female , Humans , Male , Biomarkers , C-Reactive Protein/metabolism , Depression/etiology , Prospective Studies , Risk Factors , Stroke/complications , Stroke/diagnosis , Middle Aged , Aged, 80 and overABSTRACT
BACKGROUND AND OBJECTIVE: Major depressive disorder (MDD) is associated with increased cardiac morbidity. Reduced heart rate variability (HRV) as well as lower interoceptive accuracy (IAc) have been observed in MDD as possible sympathomimetic mechanisms related to insula activity. The salience network (SN) anchored by the insula has been posited as a crucial functional network for cardiac sensations and the default mode network (DMN) for MDD. This study aimed to investigate the relation between insula-centered and depression-related brain networks, IAc and HRV in patients with depression as a possible mechanism by which MDD increases cardiac morbidity. METHODS: 30 depressed inpatients and 30 healthy subjects (derived from the population-based "Characteristics and Course of Heart Failure Stages A-B and Determinants of Progression" cohort study, STAAB) all over 50 years were examined. HRV and IAc were assessed via electrocardiogram and a heartbeat perception task prior to a 3 T resting-state functional magnetic resonance imaging. Seed-to-voxel resting-state functional connectivity (FC) analysis was conducted with six seeds in the insula and two seeds in the DMN. RESULTS: Depressed patients on the one hand showed decreased FC between insula cortex and frontal as well occipital cortical brain regions compared to controls. Depressed patients on the other hand exhibited higher FC between the medial prefrontal cortex and the insula cortex compared to controls. However, depressed patients did not differ in HRV nor in IAc compared to controls. CONCLUSION: Thus, differences in insula-related brain networks in depression in our study were not mirrored by differences in HRV and IAc. Future research is needed to define the mechanism by which depression increases cardiac morbidity.
Subject(s)
Depressive Disorder, Major , Middle Aged , Humans , Aged , Depressive Disorder, Major/diagnostic imaging , Heart Rate , Brain Mapping/methods , Cohort Studies , Depression/diagnostic imaging , Magnetic Resonance Imaging/methods , Rest/physiology , Brain/diagnostic imagingABSTRACT
Background: Anti-NMDA-receptor GluN1 antibodies (NMDAR1-abs) are present in an autoimmune encephalitis with severe neuropsychiatric symptoms. We aimed to estimate the impact of serum NMDAR1-abs on depressive symptoms years after first-ever ischemic stroke (IS). Methods: Data were used from the PROSpective Cohort with Incident Stroke-Berlin (PROSCIS-B; NCT01363856). Serum NMDAR1-abs (IgM/IgA/IgG) were measured within 7 days after IS using cell-based assays. We defined seropositivity as titers ≥1:10, thereof low titers as ≤1:100 and high titers as >1:100. We used the Center for Epidemiological Studies-Depression (CES-D) scale to measure depressive symptoms at year one, two and three following IS. We calculated crude and confounder adjusted weighted generalized linear models to quantify the impact of NMDAR1-abs on CES-D assessed at three annual time-points. Results: NMDAR1-abs were measured in 583 PROSCIS-B IS patients (mean age = 67 [SD = 13]; 42%female; median NIHSS = 2 [IQR = 1-4]) of whom 76 (13%; IgM: n = 49/IgA: n = 43/IgG: n = 2) were seropositive, 55 (9%) with low and 21 (4%) with high titers. CES-D regarded over all follow-up time-points was higher in seropositive patients (ßcrude = 2.56 [95%CI = -0.34 to 5.45]; ßadjusted = 2.26 [95%CI = -0.68 to 5.20]) and effects were highest in patients with high titer (low titers: ßcrude = 1.42 [95%CI = -1.79 to 4.62], ßadjusted = 0.53 [95%CI = -2.47 to 3.54]; high titers: ßcrude = 5.85 [95%CI = 0.20 to 11.50]; ßadjusted = 7.20 [95%CI = 0.98 to 13.43]). Conclusion: Patients with serum NMDAR1-abs (predominantly IgM&IgA) suffer more severe depressive symptoms after mild-to-moderate IS compared to NMDAR1-abs seronegative patients.
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BACKGROUND: Vasoregulatory autoantibodies including autoantibodies targeting G-protein-coupled receptors might play a functional role in vascular diseases. We investigated the impact of vasoregulatory autoantibodies on clinical outcome after ischemic stroke. METHODS AND RESULTS: Data were used from the PROSCIS-B (Prospective Cohort With Incident Stroke-Berlin). Autoantibody-targeting receptors such as angiotensin II type 1 receptor (AT1R), endothelin-1 type A receptor, complement factor-3 and -5 receptors, vascular endothelial growth factor receptor-1 and -2, vascular endothelial growth factor A and factor B were measured. We explored associations of high antibody levels with (1) poor functional outcome defined as modified Rankin Scale >2 or Barthel Index <60 at 1 year after stroke, (2) Barthel Index scores over time using general estimating equations, and (3) secondary vascular events (recurrent stroke, myocardial infarction) or death up to 3 years using Cox proportional hazard models. We included 491 patients with ischemic stroke with data on autoantibody levels and outcome. In models adjusted for demographics and vascular risk factors, high autoantibody concentrations (quartile 4) targeting complement factor C3a receptor, vascular endothelial growth factor receptor-2, and vascular endothelial growth factor B were associated with poor functional outcome at 1 year: (odds ratio, 2.0 [95% CI, 1.1-3.6]; odds ratio, 1.8 [95% CI, 1.1-3.2]; and odds ratio, 2.1 [95% CI, 1.2-3.6], respectively) and with lower Barthel Index scores over 3 years (complement factor C3a receptor: adjusted ß=-3.3 [95% CI, -5.7 to -0.5]; VEGF-B: adjusted ß=-2.4 [95% CI, -4.8 to -0.06]). Patients with high autoantibody levels were not at higher risk for secondary vascular events or death. CONCLUSIONS: High levels of autoantibodies against vascular endothelial growth factor receptor-2, vascular endothelial growth factor B, and complement factor C3a receptor measured are associated with poor functional outcome after stroke but not with recurrent vascular events or death. REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifier: NCT01363856.
Subject(s)
Ischemic Stroke , Stroke , Humans , Vascular Endothelial Growth Factor A , Vascular Endothelial Growth Factor B , Ischemic Stroke/complications , Vascular Endothelial Growth Factor Receptor-2 , Prospective Studies , Autoantibodies , Stroke/diagnosis , Stroke/complicationsABSTRACT
We aimed to assess the prognostic value of serum ß-synuclein (ß-syn), neurofilament light chain (NfL) and glial fibrillary acidic protein (GFAP) in patients with moderate-to-severe acute ischemic stroke. We measured ß-syn, GFAP and NfL in serum samples collected one day after admission in 30 adult patients with moderate-to-severe ischemic stroke due to middle cerebral artery (MCA) occlusion. We tested the associations between biomarker levels and clinical and radiological scores (National Institute of Health Stroke Scale scores, NIHSS, and Alberta Stroke Program Early CT Score, ASPECTS), as well as measures of functional outcome (modified Rankin Scale, mRS). Serum biomarkers were significantly associated with ASPECTS values (ß-syn p = 0.0011, GFAP p = 0.0002) but not with NIHSS scores at admission. Patients who received mechanical thrombectomy and intravenous thrombolysis showed lower ß-syn (p = 0.029) und NfL concentrations (p = 0.0024) compared to patients who received only mechanical thrombectomy. According to median biomarker levels, patients with high ß-syn, NfL or GFAP levels showed, after therapy, lower clinical improvement (i.e., lower 24-h NIHSS change), higher NIHSS scores during hospitalization and higher mRS scores at 3-month follow-up. Elevated serum concentrations of ß-syn (p = 0.016), NfL (p = 0.020) or GFAP (p = 0.010) were significantly associated with 3-month mRS of 3-6 vs. 0-2 even after accounting for age, sex and renal function. In patients with moderate-to-severe acute ischemic stroke, serum ß-syn, NfL and GFAP levels associated with clinical and radiological scores at different timepoints and were able to predict short- and middle-term clinical outcomes.
Subject(s)
Ischemic Stroke , Stroke , Adult , Humans , beta-Synuclein , Biomarkers , Glial Fibrillary Acidic Protein , Infarction, Middle Cerebral Artery , Intermediate Filaments , Neurofilament Proteins , Prognosis , Stroke/therapyABSTRACT
PURPOSE: Breast cancer survivors are more likely to report psychological distress and unmet need for support compared to healthy controls. Psychological mobile health interventions might be used in follow-up care of breast cancer patients to improve their mental health. METHODS: We searched MEDLINE, PsychINFO, Cochrane and PROSPERO for articles on controlled trials examining the effectiveness of psychological mobile health interventions compared to routine care regarding mental health outcomes of adult breast cancer survivors. This review followed the PRISMA statement and was registered on PROSPERO (CRD42022312972). Two researchers independently reviewed publications, extracted data and assessed risk of bias. RESULTS: After screening 204 abstracts published from 2005 to February 2023, eleven randomised trials involving 2249 patients with a mean age between 43.9 and 56.2 years met the inclusion criteria. All interventions used components of cognitive behavioural therapy. Most studies applied self-guided interventions. Five studies reported percentages of patients never started (range = 3-15%) or discontinued the intervention earlier (range = 3-36%). No long-term effect > 3 months post intervention was reported. Three of seven studies reported a significant short-term intervention effect for distress. Only one study each showed an effect for depression (1/5), anxiety (1/5), fear of recurrence (1/4) and self-efficacy (1/3) compared to a control group. CONCLUSIONS: A wide variance of interventions was used. Future studies should follow guidelines in developing and reporting their mobile interventions and conduct long-term follow-up to achieve reliable and comparable results. IMPLICATIONS FOR CANCER SURVIVORS: No clear effect of psychological mobile health interventions on patients' mental health could be shown. REGISTRATION: PROSPERO ID 312972.
ABSTRACT
AIMS: Left atrial catheter ablation is well established in patients with symptomatic atrial fibrillation (AF) but associated with risk of embolism to the brain. The present analysis aims to assess the impact of diffusion-weighted imaging (DWI) slice thickness on the rate of magnetic resonance imaging (MRI)-detected ischaemic brain lesions after ablation. METHODS AND RESULTS: AXAFA-AFNET 5 trial (NCT02227550) participants underwent MRI using high-resolution (hr) DWI (slice thickness: 2.5-3â mm) and standard DWI (slice thickness: 5-6â mm) within 3-48â h after ablation. In 321 patients with analysable brain MRI (mean age 64 years, 33% female, median CHA2DS2-VASc 2), hrDWI detected at least one acute brain lesion in 84 (26.2%) patients and standard DWI in 60 (18.7%; P < 0.01) patients. High-resolution diffusion-weighted imaging detected more lesions compared to standard DWI (165 vs. 104; P < 0.01). The degree of agreement for lesion confirmation using hrDWI vs. standard DWI was substantial (κ = 0769). Comparing the proportion of DWI-detected lesions, lesion distribution, and total lesion volume per patient, there was no difference in the cohort of participants undergoing MRI at 1.5â T (n = 52) vs. 3â T (n = 269). CONCLUSION: The pre-specified AXAFA-AFNET 5 sub-analysis revealed significantly increased rates of MRI-detected acute brain lesions using hrDWI instead of standard DWI in AF patients undergoing ablation. In comparison to DWI slice thickness, MRI field strength had a no significant impact in the trial. Comparing the varying rates of ablation-related MRI-detected brain lesions across previous studies has to consider these technical parameters. Future studies should use hrDWI, as feasibility was demonstrated in the multicentre AXAFA-AFNET 5 trial.
Subject(s)
Atrial Fibrillation , Catheter Ablation , Humans , Female , Middle Aged , Male , Magnetic Resonance Imaging/methods , Diffusion Magnetic Resonance Imaging/methods , Brain/diagnostic imaging , Atrial Fibrillation/diagnostic imaging , Atrial Fibrillation/surgery , Catheter Ablation/adverse effectsABSTRACT
BACKGROUND: Metabolic dysfunction-associated steatotic liver disease (MASLD) imposes a significant burden on Westernized regions. The Western diet, high in salt intake, significantly contributes to disease development. However, there are a lack of data on salt literacy and salt intake among MASLD patients in Germany. Our study aims to analyze daily salt intake and salt-intake-related behavior in MASLD patients. METHODS: 234 MASLD patients were prospectively included. Daily salt intake and salt-intake-related behavior were assessed via a food frequency questionnaire (FFQ-DEGS) and a salt questionnaire (SINU). Statistical analyses were performed using SPSS. RESULTS: Mean daily salt intake was higher in men than in women (7.3 ± 5 g/d vs. 5.3 ± 4 g/d; p < 0.001). There was significant agreement between increased daily salt intake (>6 g/d) and the behavioral salt index (SI) (p < 0.001). Men exhibited higher SI scores compared to women, indicating lower awareness of salt in everyday life. Multivariate analysis identified specific salt-intake-related behaviors impacting daily salt consumption. CONCLUSIONS: Our study reveals a strong link between daily salt intake and salt-intake-related behavior, highlighting sex-specific differences in an MASLD cohort. To enhance patient care in high-cardiovascular-risk populations, specific behavioral approaches may be considered, including salt awareness, to improve adherence to lifestyle changes, particularly in male patients.