Self-supervised learning for classifying paranasal anomalies in the maxillary sinus.

PURPOSE: Paranasal anomalies, frequently identified in routine radiological screenings, exhibit diverse morphological characteristics. Due to the diversity of anomalies, supervised learning methods require large labelled dataset exhibiting diverse anomaly morphology. Self-supervised learning (SSL) can be used to learn representations from unlabelled data. However, there are no SSL methods designed for the downstream task of classifying paranasal anomalies in the maxillary sinus (MS). METHODS: Our approach uses a 3D convolutional autoencoder (CAE) trained in an unsupervised anomaly detection (UAD) framework. Initially, we train the 3D CAE to reduce reconstruction errors when reconstructing normal maxillary sinus (MS) image. Then, this CAE is applied to an unlabelled dataset to generate coarse anomaly locations by creating residual MS images. Following this, a 3D convolutional neural network (CNN) reconstructs these residual images, which forms our SSL task. Lastly, we fine-tune the encoder part of the 3D CNN on a labelled dataset of normal and anomalous MS images. RESULTS: The proposed SSL technique exhibits superior performance compared to existing generic self-supervised methods, especially in scenarios with limited annotated data. When trained on just 10% of the annotated dataset, our method achieves an area under the precision-recall curve (AUPRC) of 0.79 for the downstream classification task. This performance surpasses other methods, with BYOL attaining an AUPRC of 0.75, SimSiam at 0.74, SimCLR at 0.73 and masked autoencoding using SparK at 0.75. CONCLUSION: A self-supervised learning approach that inherently focuses on localizing paranasal anomalies proves to be advantageous, particularly when the subsequent task involves differentiating normal from anomalous maxillary sinuses. Access our code at https://github.com/mtec-tuhh/self-supervised-paranasal-anomaly .

Reduced olfactory bulb volume accompanies olfactory dysfunction after mild SARS-CoV-2 infection.

Despite its high prevalence, the determinants of smelling impairment in COVID-19 remain not fully understood. In this work, we aimed to examine the association between olfactory bulb volume and the clinical trajectory of COVID-19-related smelling impairment in a large-scale magnetic resonance imaging (MRI) analysis. Data of non-vaccinated COVID-19 convalescents recruited within the framework of the prospective Hamburg City Health Study COVID Program between March and December 2020 were analyzed. At baseline, 233 participants underwent MRI and neuropsychological testing as well as a structured questionnaire for olfactory function. Between March and April 2022, olfactory function was assessed at follow-up including quantitative olfactometric testing with Sniffin' Sticks. This study included 233 individuals recovered from mainly mild to moderate SARS-CoV-2 infections. Longitudinal assessment demonstrated a declining prevalence of self-reported olfactory dysfunction from 67.1% at acute infection, 21.0% at baseline examination and 17.5% at follow-up. Participants with post-acute self-reported olfactory dysfunction had a significantly lower olfactory bulb volume at baseline than normally smelling individuals. Olfactory bulb volume at baseline predicted olfactometric scores at follow-up. Performance in neuropsychological testing was not significantly associated with the olfactory bulb volume. Our work demonstrates an association of long-term self-reported smelling dysfunction and olfactory bulb integrity in a sample of individuals recovered from mainly mild to moderate COVID-19. Collectively, our results highlight olfactory bulb volume as a surrogate marker that may inform diagnosis and guide rehabilitation strategies in COVID-19.

Computer-Aided Diagnosis of Maxillary Sinus Anomalies: Validation and Clinical Correlation.

OBJECTIVE: Computer aided diagnostics (CAD) systems can automate the differentiation of maxillary sinus (MS) with and without opacification, simplifying the typically laborious process and aiding in clinical insight discovery within large cohorts. METHODS: This study uses Hamburg City Health Study (HCHS) a large, prospective, long-term, population-based cohort study of participants between 45 and 74 years of age. We develop a CAD system using an ensemble of 3D Convolutional Neural Network (CNN) to analyze cranial MRIs, distinguishing MS with opacifications (polyps, cysts, mucosal thickening) from MS without opacifications. The system is used to find correlations of participants with and without MS opacifications with clinical data (smoking, alcohol, BMI, asthma, bronchitis, sex, age, leukocyte count, C-reactive protein, allergies). RESULTS: The evaluation metrics of CAD system (Area Under Receiver Operator Characteristic: 0.95, sensitivity: 0.85, specificity: 0.90) demonstrated the effectiveness of our approach. MS with opacification group exhibited higher alcohol consumption, higher BMI, higher incidence of intrinsic asthma and extrinsic asthma. Male sex had higher prevalence of MS opacifications. Participants with MS opacifications had higher incidence of hay fever and house dust allergy but lower incidence of bee/wasp venom allergy. CONCLUSION: The study demonstrates a 3D CNN's ability to distinguish MS with and without opacifications, improving automated diagnosis and aiding in correlating clinical data in population studies. LEVEL OF EVIDENCE: 3 Laryngoscope, 2024.

Multiple instance ensembling for paranasal anomaly classification in the maxillary sinus.

PURPOSE: Paranasal anomalies are commonly discovered during routine radiological screenings and can present with a wide range of morphological features. This diversity can make it difficult for convolutional neural networks (CNNs) to accurately classify these anomalies, especially when working with limited datasets. Additionally, current approaches to paranasal anomaly classification are constrained to identifying a single anomaly at a time. These challenges necessitate the need for further research and development in this area. METHODS: We investigate the feasibility of using a 3D convolutional neural network (CNN) to classify healthy maxillary sinuses (MS) and MS with polyps or cysts. The task of accurately localizing the relevant MS volume within larger head and neck Magnetic Resonance Imaging (MRI) scans can be difficult, but we develop a strategy which includes the use of a novel sampling technique that not only effectively localizes the relevant MS volume, but also increases the size of the training dataset and improves classification results. Additionally, we employ a Multiple Instance Ensembling (MIE) prediction method to further boost classification performance. RESULTS: With sampling and MIE, we observe that there is consistent improvement in classification performance of all 3D ResNet and 3D DenseNet architecture with an average AUPRC percentage increase of 21.86 ± 11.92% and 4.27 ± 5.04% by sampling and 28.86 ± 12.80% and 9.85 ± 4.02% by sampling and MIE, respectively. CONCLUSION: Sampling and MIE can be effective techniques to improve the generalizability of CNNs for paranasal anomaly classification. We demonstrate the feasibility of classifying anomalies in the MS. We propose a data enlarging strategy through sampling alongside a novel MIE strategy that proves to be beneficial for paranasal anomaly classification in the MS.

Increased blood pressure after nonsevere COVID-19.

BACKGROUND: Various sequelae have been described after nonsevere coronavirus disease 2019 (COVID-19), but knowledge on postacute effects on blood pressure is limited. METHODS: This is a cross-sectional analysis of blood pressure profiles in individuals after nonsevere COVID-19 compared with matched population-based individuals without prior COVID-19. Data were derived from the ongoing and prospective Hamburg City Health Study, a population-based study in Hamburg, Germany, and its associated COVID-19 program, which included individuals at least 4 months after COVID-19. Matching was performed by age, sex, education, and preexisting hypertension in a 1 : 4 ratio. RESULTS: Four hundred and thirty-two individuals after COVID-19 (mean age 56.1 years) were matched to 1728 controls without prior COVID-19 (56.2 years). About 92.8% of COVID-19 courses were mild or moderate, only 7.2% were hospitalized, and no individual had been treated on an intensive care unit. Even after adjustment for relevant competing risk factors, DBP [+4.7 mmHg, 95% confidence interval (95% CI) 3.97-5.7, P  < 0.001] was significantly higher in individuals after COVID-19. For SBP, a trend towards increased values was observed (+1.4 mmHg, 95% CI -0.4 to 3.2, P  = 0.120). Hypertensive blood pressures at least 130/80 mmHg (according to the ACC/AHA guideline) and at least 140/90 mmHg (ESC/ESH guideline) occurred significantly more often in individuals after COVID-19 than matched controls (odds ratio 2.0, 95% CI 1.5-2.7, P  < 0.001 and odds ratio 1.6, 95% CI 1.3-2.0, P  < 0.001, respectively), mainly driven by changes in DBP. CONCLUSION: Blood pressure is higher in individuals after nonsevere COVID-19 compared with uninfected individuals suggesting a significant hypertensive sequela.

Association between an Anti-Inflammatory Dietary Score and Periodontitis-Evidence from the Population-Based Hamburg City Health Study.

While the effects of dietary patterns on cardiovascular risk and diabetes have been well studied, the evidence is scarce as to which diet has the greatest anti-inflammatory potential and how dietary patterns are associated with periodontitis. In the Hamburg City Health Study (HCHS), we developed an anti-inflammatory dietary score using a data-driven approach based on the relationship of relevant selected food groups with inflammatory biomarkers (hsCRP and IL-6). The aim of this cross-sectional study was to evaluate the association between the anti-inflammatory dietary score and the incidence of periodontitis in Hamburg, Germany. A total of n = 5642 participants fit the required inclusion criteria and were selected for analysis. Periodontal disease was assessed using probing depth, gingival recession, and bleeding on probing. Dietary intake was measured using a food frequency questionnaire (FFQ). A self-developed anti-inflammatory dietary score served as the key explanatory variable. Higher scores reflected lower inflammatory processes (measured through the biomarkers hsCRP and IL-6). Several covariates were included in the regression analysis. Regressions revealed that a higher anti-inflammatory dietary score was significantly associated with lower odds to be affected by periodontal disease in an unadjusted model (OR 0.86, 95% CI 0.82-0.89, p < 0.001) and in an adjusted model (age, sex, smoking, diabetes, hypertension, and physical activity) (OR 0.93, 95% CI 0.89-0.98, p = 0.003). Our study demonstrated a significant inverse association between an anti-inflammatory dietary score and periodontitis. Individuals with higher intake of proinflammatory nutrition should be specifically addressed to avoid periodontitis.

Brain imaging and neuropsychological assessment of individuals recovered from a mild to moderate SARS-CoV-2 infection.

As severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2) infections have been shown to affect the central nervous system, the investigation of associated alterations of brain structure and neuropsychological sequelae is crucial to help address future health care needs. Therefore, we performed a comprehensive neuroimaging and neuropsychological assessment of 223 nonvaccinated individuals recovered from a mild to moderate SARS-CoV-2 infection (100 female/123 male, age [years], mean ± SD, 55.54 ± 7.07; median 9.7 mo after infection) in comparison with 223 matched controls (93 female/130 male, 55.74 ± 6.60) within the framework of the Hamburg City Health Study. Primary study outcomes were advanced diffusion MRI measures of white matter microstructure, cortical thickness, white matter hyperintensity load, and neuropsychological test scores. Among all 11 MRI markers tested, significant differences were found in global measures of mean diffusivity (MD) and extracellular free water which were elevated in the white matter of post-SARS-CoV-2 individuals compared to matched controls (free water: 0.148 ± 0.018 vs. 0.142 ± 0.017, P < 0.001; MD [10-3 mm2/s]: 0.747 ± 0.021 vs. 0.740 ± 0.020, P < 0.001). Group classification accuracy based on diffusion imaging markers was up to 80%. Neuropsychological test scores did not significantly differ between groups. Collectively, our findings suggest that subtle changes in white matter extracellular water content last beyond the acute infection with SARS-CoV-2. However, in our sample, a mild to moderate SARS-CoV-2 infection was not associated with neuropsychological deficits, significant changes in cortical structure, or vascular lesions several months after recovery. External validation of our findings and longitudinal follow-up investigations are needed.

Cross-Sectional Association of Dietary Patterns and Supplement Intake with Presence and Gray-Scale Median of Carotid Plaques-A Comparison between Women and Men in the Population-Based Hamburg City Health Study.

This population-based cross-sectional cohort study investigated the association of the Mediterranean and DASH (Dietary Approach to Stop Hypertension) diet as well as supplement intake with gray-scale median (GSM) and the presence of carotid plaques comparing women and men. Low GSM is associated with plaque vulnerability. Ten thousand participants of the Hamburg City Health Study aged 45-74 underwent carotid ultrasound examination. We analyzed plaque presence in all participants plus GSM in those having plaques (n = 2163). Dietary patterns and supplement intake were assessed via a food frequency questionnaire. Multiple linear and logistic regression models were used to assess associations between dietary patterns, supplement intake and GSM plus plaque presence. Linear regressions showed an association between higher GSM and folate intake only in men (+9.12, 95% CI (1.37, 16.86), p = 0.021). High compared to intermediate adherence to the DASH diet was associated with higher odds for carotid plaques (OR = 1.18, 95% CI (1.02, 1.36), p = 0.027, adjusted). Odds for plaque presence were higher for men, older age, low education, hypertension, hyperlipidemia and smoking. In this study, the intake of most supplements, as well as DASH or Mediterranean diet, was not significantly associated with GSM for women or men. Future research is needed to clarify the influence, especially of the folate intake and DASH diet, on the presence and vulnerability of plaques.

Performance of an interferon-γ release assay-based test for cell-mediated immunity to SARS-CoV-2.

In search for immunological correlates of protection against acute coronavirus disease 2019 (COVID-19) there is a need for high through-put assays for cell-mediated immunity (CMI) to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. We established an interferon-γ release assay -based test for detection of CMI against SARS-CoV-2 spike (S) or nucleocapsid (NC) peptides. Blood samples obtained from 549 healthy or convalescent individuals were measured for interferon-γ (IFN-γ) production after peptide stimulation using a certified chemiluminescence immunoassay. Test performance was calculated applying cutoff values with the highest Youden indices in receiver-operating-characteristics curve analysis and compared to a commercially available serologic test. Potential confounders and clinical correlates were assessed for all test systems. 522 samples obtained from 378 convalescent in median 298 days after PCR-confirmed SARS-CoV-2 infection and 144 healthy control individuals were included in the final analysis. CMI testing had a sensitivity and specificity of up to 89% and 74% for S peptides and 89% and 91% for NC peptides, respectively. High white blood cell counts correlated negatively with IFN-γ responses but there was no CMI decay in samples obtained up to one year after recovery. Severe clinical symptoms at time of acute infection were associated with higher measures of adaptive immunity and reported hair loss at time of examination. This laboratory-developed test for CMI to SARS-CoV-2 NC peptides exhibits excellent test performance, is suitable for high through-put routine diagnostics, and should be evaluated for clinical outcome prediction in prospective pathogen re-exposure.

[Non-utilisation of medical services during the COVID-19 pandemic among persons with chronic diseases]. / Nichtinanspruchnahme medizinischer Leistungen in der COVID-19-Pandemie bei Personen mit chronischen Erkrankungen.

INTRODUCTION: The COVID-19 pandemic is also impacting the medical care for other diseases. The extent to which people with chronic diseases are affected by the suspension of medical services is investigated-differentiating between patient and provider perspectives. METHOD: A cross-sectional study was conducted based on data from the longitudinal Hamburg City Health Study (HCHS). The study population was all HCHS participants (a sample of the population of Hamburg, 45-74 years) between April 2020 and November 2021. Utilisation of medical services was collected via the "COVID-19-module" of the HCHS. The chronic conditions included cardiovascular disease, kidney and lung disease, cancer and diabetes mellitus; analyses were descriptive and multivariate. RESULTS: Of the 2047 participants, 47.9% had at least one previous illness. Of those with pre-existing conditions, 21.4% had at least one healthcare service suspended or an appointment cancelled. In addition, 15.4% stated that they decided by themselves not to attend a doctor's appointment. Specialist care services (43.8% of all cancellations) were cancelled more frequently than general practitioner care (16.6%). After adjustment for age, gender and education, lung disease (OR 1.80; p < 0.008) and cancer (OR 2.33; p < 0.001) were found to be independent risk factors for appointment cancellations by healthcare providers. Of cancellations by patients, 42.2% were due to their fear of an infection with the coronavirus SARS-CoV­2. DISCUSSION: Health policy and the media are faced with the challenge of dealing with fears of infection in the population in such a way that they do not lead to an avoidance of necessary care services.

Editor's Choice - Prevalence of Peripheral Arterial Disease, Abdominal Aortic Aneurysm, and Risk Factors in the Hamburg City Health Study: A Cross Sectional Analysis.

OBJECTIVE: There is a paucity of current figures on the prevalence of carotid and lower extremity peripheral arterial disease (PAD) and abdominal aortic aneurysm (AAA) as well as the associated cardiovascular risk factors to support considerations on screening programmes. METHODS: In the population based Hamburg City Health Study, participants between 45 and 74 years were randomly recruited. In the current cross sectional analysis of the first 10 000 participants enrolled between February 2016 and November 2018, the prevalence of carotid artery disease (intima-media thickness ≥ 1 mm), lower extremity PAD (ankle brachial index ≤ 0.9), and AAA (aortic diameter ≥ 30 mm) was determined. Multivariable logistic regression models were applied to determine the association between vascular diseases and risk factors. To account for missing values, multiple imputation was performed. RESULTS: A total of 10 000 participants were analysed (51.1% females, median age 63 years, median body mass index 26.1 kg/m2). In medians, the intima media thickness was 0.74 mm (interquartile range [IQR] 0.65 - 0.84), the ankle brachial index 1.04 (IQR 0.95 - 1.13), and the aortic diameter 17.8 mm (IQR 16.1 - 19.6). Concerning risk factors, 64% self reported any smoking, 39% hypertension, 5% coronary artery disease, 3% congestive heart failure, 5% atrial fibrillation, and 3% history of stroke or myocardial infarction, respectively. In males, the prevalence of carotid artery disease, lower extremity PAD, and AAA were 35.3%, 22.7%, and 1.3%, respectively, and in females, 23.4%, 24.8%, and 0.2%, respectively. Higher age and current smoking were likewise associated with higher prevalence while the impact of variables varied widely. CONCLUSION: In this large population based cohort study of 10 000 subjects from Hamburg, Germany, a strikingly high prevalence of PAD was revealed. Almost 45% suffered from any index disease, while AAA was only diagnosed in 1.3% of males and 0.2% of females. The high prevalence of atherosclerotic disease and associated cardiovascular risk factors underline that it is essential to increase awareness and fuel efforts for secondary prevention.

Kidney outcome after mild to moderate COVID-19.

BACKGROUND: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has a remarkable kidney tropism. While kidney effects are common in severe coronavirus disease 2019 (COVID-19), data on non-severe courses are limited. Here we provide a multilevel analysis of kidney outcomes after non-severe COVID-19 to test for eventual kidney sequela. METHODS: This cross-sectional study investigates individuals after COVID-19 and matched controls recruited from the Hamburg City Health Study (HCHS) and its COVID-19 program. The HCHS is a prospective population-based cohort study within the city of Hamburg, Germany. During the COVID-19 pandemic the study additionally recruited subjects after polymerase chain reaction-confirmed SARS-CoV-2 infections. Matching was performed by age, sex and education. Main outcomes were estimated glomerular filtration rate (eGFR), albuminuria, Dickkopf3, haematuria and pyuria. RESULTS: A total of 443 subjects in a median of 9 months after non-severe COVID-19 were compared with 1328 non-COVID-19 subjects. The mean eGFR was mildly lower in post-COVID-19 than non-COVID-19 subjects, even after adjusting for known risk factors {ß = -1.84 [95% confidence interval (CI) -3.16 to -0.52]}. However, chronic kidney disease [odds ratio (OR) 0.90 (95% CI 0.48-1.66)] or severely increased albuminuria [OR 0.76 (95% CI 0.49-1.09)] equally occurred in post-COVID-19 and non-COVID-19 subjects. Haematuria, pyuria and proteinuria were also similar between the two cohorts, suggesting no ongoing kidney injury after non-severe COVID-19. Further, Dickkopf3 was not increased in the post-COVID-19 cohort, indicating no systematic risk for ongoing GFR decline [ß = -72.19 (95% CI -130.0 to -14.4)]. CONCLUSION: While mean eGFR was slightly lower in subjects after non-severe COVID-19, there was no evidence for ongoing or progressive kidney sequela.

Brain network architecture constrains age-related cortical thinning.

Age-related cortical atrophy, approximated by cortical thickness measurements from magnetic resonance imaging, follows a characteristic pattern over the lifespan. Although its determinants remain unknown, mounting evidence demonstrates correspondence between the connectivity profiles of structural and functional brain networks and cortical atrophy in health and neurological disease. Here, we performed a cross-sectional multimodal neuroimaging analysis of 2633 individuals from a large population-based cohort to characterize the association between age-related differences in cortical thickness and functional as well as structural brain network topology. We identified a widespread pattern of age-related cortical thickness differences including "hotspots" of pronounced age effects in sensorimotor areas. Regional age-related differences were strongly correlated within the structurally defined node neighborhood. The overall pattern of thickness differences was found to be anchored in the functional network hierarchy as encoded by macroscale functional connectivity gradients. Lastly, the identified difference pattern covaried significantly with cognitive and motor performance. Our findings indicate that connectivity profiles of functional and structural brain networks act as organizing principles behind age-related cortical thinning as an imaging surrogate of cortical atrophy.

Detection of stage I HPV-driven oropharyngeal cancer in asymptomatic individuals in the Hamburg City Health Study using HPV16 E6 serology - A proof-of-concept study.

Background: The lack of detectable precancerous lesions poses challenges to the early detection of human papillomavirus-driven oropharyngeal cancer (HPV-OPC). Antibodies against HPV16 early proteins, especially E6, are uniquely sensitive and specific biomarkers detectable years prior to HPV-OPC diagnosis. Thus, HPV16 early protein serology warrants clinical investigation for HPV-OPC screening. Methods: Using multiplex serology, we analyzed HPV16 serum antibodies of the first 5000 participants (n=4,424 sera, recruited 2016-2017) of the Hamburg City Health Study, a population-based prospective cohort (45-74 years). Participants seropositive for HPV16 E6 and at least one additional early protein (E1, E2, E7) were considered at high risk for HPV-OPC development and invited to six-monthly non-invasive head and neck follow-up (FU) examinations (visual inspection, endoscopy, ultrasonography, performed 2019-2020). Participants with suspicious lesions were examined by magnetic resonance imaging and panendoscopy with biopsy. Histologically confirmed OPC cases were treated according to standard of care. Findings: In total, 35 out of 4,424 study participants (0·8%, 95% confidence interval (CI) 0·6-1·1%) were HPV16 E6 seropositive. Among these, eleven (0·3%, 95%CI 0·1-0·5%) were considered at high risk for HPV-OPC of which nine were successfully re-contacted and invited to regular clinical FU examinations. Two males and one female were diagnosed with stage I HPV-OPC within 1·3 years of clinical FU (3-4 years after initial blood draw), representing one diagnosis of prevalent advanced disease, one incident diagnosis of advanced disease, and one incident diagnosis of early disease. The remaining participants showed no detectable signs of cancer, and undergo regular examinations (median clinical FU: 1·0 years, median total FU from blood draw to last clinical FU visit: 4·7 years). Interpretation: HPV16 early antibodies allowed identifying three asymptomatic stage I HPV-OPC patients, out of eleven participants considered at high risk. However, two of the three cases already showed signs of advanced disease at diagnosis. Targeting multiple early proteins may considerably improve the positive predictive value of HPV16 serology and may have clinical utility for HPV-OPC screening. Funding: This work was funded by DKFZ and UKE intramural funding.

Association of Carotid Plaque and Flow Velocity With White Matter Integrity in a Middle-aged to Elderly Population.

BACKGROUND AND OBJECTIVES: It is uncertain whether there is an association of carotid plaques (CP) and flow velocities with peak-width mean diffusivity (PSMD) and white matter hyperintensities (WMH) independent of shared risk factors. We aimed to study this association controlling for biomarkers of inflammation and cardiac dysfunction as well as typical cardiovascular risk factors and spatial distribution. METHODS: We included participant from the population-based Hamburg City Health Study, recruiting citizens between 45 and 74 years of age. Medical history was obtained from structured interviews and extended laboratory tests, physical examinations, MRI of the head, echocardiography, abdominal and carotid ultrasound were performed. We performed multivariable regression analysis with PSMD, periventricular, deep, and total volume of WMH (pWMH, dWMH, tWMH) as dependent variables. PSMD was calculated as the difference between the 95th and 5th percentile of MD values on the white skeleton in standard space Volumes of WMH were determined by application of a manually trained k-nearest neighbor segmentation algorithm. WMH measured within a distance of 1 cm from the surface of the lateral ventricles were defined as pWMH, and above 1 cm as dWMH. RESULTS: 2623 participants were included. Median age was 65 years and 56% were women. Their median tWMH was 946 mm3(IQR:419, 2164), PSMD 2.24 mm2 /s x 10-4 (IQR: 2.04,2.47), peak systolic velocity (PSV) of internal carotid arteries 0.70m/sec (IQR:0.60, 0.81), and 35% had CP. Adjusted for age, sex, high-sensitive CRP, NT-proBNP, and commonly measured cardiovascular risk and systemic hemodynamic factors, both CP (B=0.15;CI:0.04, 0.26;p=0.006) and low PSV (B=-0.49; CI:-0.87,-0.11;p=0.012) were significantly associated with a higher tWMH and PSMD. Low PSV(B=-0.48;CI:-0.87,-0.1;p=0.013) was associated with pWMH, and presence of CP with pWMH (B=0.15; CI:0.04,0.26; p=0.008) and dWMH (B=0.42; CI:0.11,0.74; p<0.009). CONCLUSION: Low PSV and CP are associated with WMH and PSMD independent of cardiovascular risk factors and biomarkers of inflammation and cardiac dysfunction. This points towards pathophysiological pathways underlying both large and small vessel disease beyond the common cardiovascular risk profile. TRIAL REGISTRATION INFORMATION: The trial was submitted at www. CLINICALTRIALS: gov, under NCT03934957 on January 4 2019. The first participant was enrolled in February 2016.

Free-water diffusion MRI detects structural alterations surrounding white matter hyperintensities in the early stage of cerebral small vessel disease.

In cerebral small vessel disease (CSVD), both white matter hyperintensities (WMH) of presumed vascular origin and the normal-appearing white matter (NAWM) contain microstructural brain alterations on diffusion-weighted MRI (DWI). Contamination of DWI-derived metrics by extracellular free-water can be corrected with free-water (FW) imaging. We investigated the alterations in FW and FW-corrected fractional anisotropy (FA-t) in WMH and surrounding tissue and their association with cerebrovascular risk factors. We analysed 1,000 MRI datasets from the Hamburg City Health Study. DWI was used to generate FW and FA-t maps. WMH masks were segmented on FLAIR and T1-weighted MRI and dilated repeatedly to create 8 NAWM masks representing increasing distance from WMH. Linear models were applied to compare FW and FA-t across WMH and NAWM masks and in association with cerebrovascular risk. Median age was 64 ± 14 years. FW and FA-t were altered 8 mm and 12 mm beyond WMH, respectively. Smoking was significantly associated with FW in NAWM (p = 0.008) and FA-t in WMH (p = 0.008) and in NAWM (p = 0.003) while diabetes and hypertension were not. Further research is necessary to examine whether FW and FA-t alterations in NAWM are predictors for developing WMH.

Multi-organ assessment in mainly non-hospitalized individuals after SARS-CoV-2 infection: The Hamburg City Health Study COVID programme.

AIMS: Long-term sequelae may occur after SARS-CoV-2 infection. We comprehensively assessed organ-specific functions in individuals after mild to moderate SARS-CoV-2 infection compared with controls from the general population. METHODS AND RESULTS: Four hundred and forty-three mainly non-hospitalized individuals were examined in median 9.6 months after the first positive SARS-CoV-2 test and matched for age, sex, and education with 1328 controls from a population-based German cohort. We assessed pulmonary, cardiac, vascular, renal, and neurological status, as well as patient-related outcomes. Bodyplethysmography documented mildly lower total lung volume (regression coefficient -3.24, adjusted P = 0.014) and higher specific airway resistance (regression coefficient 8.11, adjusted P = 0.001) after SARS-CoV-2 infection. Cardiac assessment revealed slightly lower measures of left (regression coefficient for left ventricular ejection fraction on transthoracic echocardiography -0.93, adjusted P = 0.015) and right ventricular function and higher concentrations of cardiac biomarkers (factor 1.14 for high-sensitivity troponin, 1.41 for N-terminal pro-B-type natriuretic peptide, adjusted P ≤ 0.01) in post-SARS-CoV-2 patients compared with matched controls, but no significant differences in cardiac magnetic resonance imaging findings. Sonographically non-compressible femoral veins, suggesting deep vein thrombosis, were substantially more frequent after SARS-CoV-2 infection (odds ratio 2.68, adjusted P < 0.001). Glomerular filtration rate (regression coefficient -2.35, adjusted P = 0.019) was lower in post-SARS-CoV-2 cases. Relative brain volume, prevalence of cerebral microbleeds, and infarct residuals were similar, while the mean cortical thickness was higher in post-SARS-CoV-2 cases. Cognitive function was not impaired. Similarly, patient-related outcomes did not differ. CONCLUSION: Subjects who apparently recovered from mild to moderate SARS-CoV-2 infection show signs of subclinical multi-organ affection related to pulmonary, cardiac, thrombotic, and renal function without signs of structural brain damage, neurocognitive, or quality-of-life impairment. Respective screening may guide further patient management.

Association between Dietary Pattern and Periodontitis-A Cross-Sectional Study.

The aim of the study was to investigate the relationship between specific known dietary patterns and the prevalence of periodontal disease in a northern population-based cohort study. We evaluated data from 6209 participants of the Hamburg City Health Study (HCHS). The HCHS is a prospective cohort study and is registered at ClinicalTrial.gov (NCT03934957). Dietary intake was assessed with the food frequency questionnaire (FFQ2). Periodontal examination included probing depth, gingival recession, plaque index, and bleeding on probing. Descriptive analyses were stratified by periodontitis severity. Ordinal logistic regression models were used to determine the association. Ordinal regression analyses revealed a significant association between higher adherence to the DASH diet/Mediterranean diet and lower odds to be affected by periodontal diseases in an unadjusted model (OR: 0.92; 95% CI: 0.87, 0.97; p < 0.001/OR: 0.93; 95% CI: 0.91, 0.96; p < 0.001) and an adjusted model (age, sex, diabetes) (OR: 0.94; 95% CI: 0.89, 1.00; p < 0.0365/OR: 0.97; 95% CI: 0.94, 1.00; p < 0.0359). The current cross-sectional study identified a significant association between higher adherence to the DASH and Mediterranean diets and lower odds to be affected by periodontal diseases (irrespective of disease severity). Future randomized controlled trials are needed to evaluate to which extent macro- and micronutrition can affect periodontitis initiation/progression.

Aortic root dimensions as a correlate for aortic regurgitation's severity.

To evaluate the prevalence of aortic regurgitation (AR) and associations between the individual aortic root components and AR severity in the general population. The study included the first 10,000 participants of the population-based Hamburg City Health Study (HCHS) of whom 8259 subjects, aged 62.23 ± 8.46 years (51.3% females), enrolled 2016-2018, provided echocardiographic data. 69 subjects with bicuspid valves and 23 subjects with moderate/severe aortic stenosis were excluded. Aortic root dimensions were measured using state-of-the-art cardiac ultrasound, including the aortic annulus, sinus of Valsalva, sinotubular junction (STJ), and ascending aorta, in diastole and systole. The distribution of AR was: 932 (11.4%) mild, 208 (2.5%) moderate, and 20 (0.24%) severe. Patients with moderate or severe AR were predominantly male at advanced age who had hypertension, coronary artery disease, atrial fibrillation, and renal dysfunction. Increasing AR severity correlated with higher absolute and indexed aortic root diameters (e.g., end-diastolic sinus of Valsalva for no-mild-moderate-severe AR in mm ± standard deviation: 34.06 ± 3.81; 35.65 ± 4.13; 36.13 ± 4.74; 39.67 ± 4.61; p < 0.001). In binary logistic regression analysis, all aortic root components showed significant associations with moderate/severe AR. Mid-systolic STJ showed the strongest association with moderate/severe AR (OR 1.33, 95% confidence interval 1.25-1.43, p < 0.001). AR was prevalent in 14.2%, of whom 2.8% showed moderate/severe AR. All assessed aortic root diameters correlated with the prevalence and severity of AR. STJ diameter had the strongest association with moderate/severe AR possibly reflecting the pathophysiological impact of an increasingly dilated STJ in the context of an ageing aorta.

Transthoracic echocardiographic reference values of the aortic root: results from the Hamburg City Health Study.

Here we generate up-to-date reference values of transthoracic echocardiographic aortic root dimensions matched by sex, age, and body surface area (BSA) derived from the population-based Hamburg City Health Study (HCHS) cohort. In 1687 healthy subjects (mean age 57.1 ± 7.7, 681 male and 1006 female), derived from the first prospectively-recruited 10,000 HCHS participants, dimensions of the aortic root were measured in systole and diastole using state-of-the-art 2-dimensional transthoracic echocardiography. Diameters were assessed at four levels: aortic annulus, Sinus of Valsalva, sinotubular junction, and ascending aorta. Female sex was associated with significantly smaller absolute aortic root dimensions, while indexing for BSA resulted in a reverse effect at all levels. There was a strong age dependency of all aortic root diameters as well as aortic annulus/sinotubular junction ratio for both sexes. Multivariate analysis revealed age, sex, weight, height, and BSA to be significant determinants of aortic root size. Finally, formulas were generated for the calculation of individual aortic root reference values considering age, sex, weight, and height. We provide population-based reference values of aortic root diameters based on a standardized transthoracic echocardiographic protocol of the population-based HCHS which may support the diagnosis, monitoring, and treatment of aortic root disease.