INTRO:The aim of this questionnaire survey was to analyse the approach orthodontists take on oral hygiene (OH) throughout Germany. The information orthodontists provide their patients with respect to brushing and steps the patients can take at home to achieve the best results, as well as the amount of times orthodontists scheduled controls and appointments with their patients was collected. METHODS:A computer program randomly selected 1000 members from the DGKFO directory to whom questionnaires were mailed. The size and population of the federal states (FS) were taken into account. The FS with the highest return rates (Baden-Württemberg (BW), Bavaria (B), Hesse (H), Lower Saxony (NDS), North Rhine-Westphalia (NRW)) were considered and differences between the 16 FS were divided into north, south, east and central. Data analysis was performed using cross tables and chi-square tests. RESULTS:The response rate of the questionnaires was 52.4%. The majority (53.8%) worked in one practice alone. Most (59.1%) have been orthodontists for 5-25 years. OH instructions were given orally by the dental assistant (> 90%). Multibracket appliances (MBA) were checked monthly, and removable appliances (RA) every 2 months; in over 90% at each session. Professional dental cleaning (PDC) took place every 6 months, except in NDS (every 3 months). When considering tooth brushing methods, the bass technique was specified for MBA and the Fones-technique for RA. CONCLUSION:The dental assistant gave the subjects instructions regarding oral care at home. The MBA control was carried out monthly and at RA every 2 months. PDC usually took place every 6 months.

BACKGROUND:Whether anticoagulation alone is an adequate treatment for acute, intermediate-risk pulmonary embolism is uncertain. METHODS:We conducted a multinational, adaptive-design trial with blinded outcome adjudication. Patients with intermediate-risk pulmonary embolism (with a ratio of right ventricular end-diastolic diameter to left ventricular end-diastolic diameter of ≥1.0 and an elevated troponin level) were eligible if they had at least two indicators of cardiorespiratory distress (systolic blood pressure of ≤110 mm Hg, a heart rate of ≥100 beats per minute, or a respiratory rate of >20 breaths per minute). Patients were randomly assigned to undergo ultrasound-facilitated, catheter-directed fibrinolysis with alteplase plus anticoagulation (the intervention group) or anticoagulation alone (the control group) according to prespecified treatment protocols. The primary outcome was a composite of pulmonary embolism-related death, cardiorespiratory decompensation or collapse, or symptomatic recurrence of pulmonary embolism within 7 days. RESULTS:The intention-to-treat population comprised 544 patients: 273 in the intervention group and 271 in the control group. The mean (±SD) age was 58.2±13.5 years, and 42.6% of the patients were women. A primary-outcome event occurred in 11 patients (4.0%; 95% confidence interval [CI], 2.3 to 7.1) in the intervention group and 28 (10.3%; 95% CI, 7.2 to 14.5) in the control group (relative risk, 0.39; 95% CI, 0.20 to 0.77; P = 0.005). The effect was driven primarily by a lower risk of cardiorespiratory decompensation or collapse in the intervention group. Major bleeding occurred within 7 days after randomization in 11 patients (4.1%) in the intervention group and 6 (2.2%) in the control group (P = 0.32); major bleeding occurred within 30 days in 11 patients (4.1%) and 8 patients (3.0%), respectively (P = 0.64). No substantial between-group differences in the incidence of other serious adverse events were observed up to 30 days after randomization; no intracranial hemorrhage occurred. CONCLUSIONS:In patients with acute, intermediate-risk pulmonary embolism, ultrasound-facilitated, catheter-directed fibrinolysis plus anticoagulation led to a lower risk of the composite of pulmonary embolism-related death, cardiopulmonary decompensation or collapse, or symptomatic recurrence of pulmonary embolism within 7 days than anticoagulation alone. (Funded by Boston Scientific; HI-PEITHO ClinicalTrials.gov number, NCT04790370.).

AIMS:Road traffic noise is the dominant source of environmental noise in Europe and a recognized cardiovascular risk factor, yet direct mechanistic evidence from human studies remains limited. This study investigated the acute effects of low-level night-time road traffic noise exposure on cardiovascular parameters in healthy adults. METHODS AND RESULTS:In a randomized, double-blind, crossover design, 74 healthy participants were exposed to three overnight conditions: control (no noise, average sound pressure level (LAeq) 30.70 dB), 30 (LAeq 41.36), and 60 (LAeq 44.13) recorded road traffic noise events (peak level ≈60 dB). The primary endpoint was endothelial function assessed by flow-mediated dilation (FMD) the morning after each night; a subgroup received vitamin C to assess oxidative stress involvement. Secondary endpoints included sleep quality (questionnaires), cardiovascular parameters (blood pressure, heart rate, electrocardiogram), and targeted proteomic analysis (Olink panels). FMD significantly decreased from 9.35% (control) to 8.19% after 30 noise events (Δ = 1.16%, P = 0.005) and 7.73% after 60 events (Δ = 1.63%, P < 0.0001), with the strongest FMD improvement by vitamin C in the 60-event condition (Δ = 1.02%). Noise exposure increased heart rate (mean difference Δ = 1.23 bpm, P = 0.04; max Δ = 7.95 bpm, P < 0.001) and the odds of post-noise heart rate peaks (odds ratio 2.42, 95% confidence interval 2.07-2.83). After noise exposure, self-reported sleep quality and restfulness were significantly impaired across all dimensions. Clinical chemistry blood parameters did not change significantly. Proteomic analysis revealed noise-associated changes in interleukin signalling and chemotaxis in participants with the strongest FMD impairments. CONCLUSION:Acute exposure to night-time road traffic noise leads to measurable changes in cardiovascular health parameters in healthy adults. These effects were linked to activation of molecular pathways of immune signalling. Plasma proteome changes were correlated to FMD changes (responders vs. non-responders), highlighting interindividual biological susceptibility to noise.

Abstract The objective of this study was to analyze visual perception of patients undergoing orthodontic treatment with multi-bracket appliances (MBA), and examine differences in oral hygiene perception among adolescents, their guardians, and dental students. The lay person group included 56 participants (28 adolescents and guardians), while the expert group consisted of 30 dentistry students. Both groups evaluated randomized intraoral frontal photographs of adolescents with MBA, taken with or without a plaque disclosing agent. Using eye-tracking methods, eye movements were recorded during the evaluation. Significant differences in visual path length and oral hygiene evaluation were found. The expert group evaluated oral hygiene most accurately, with parents being stricter and adolescents more lenient. The expert group’s visual path was significantly shorter than the lay person group’s. Use of a plaque disclosing agent improved the accuracy of oral hygiene evaluation ( p < 0.001). A correlation was observed between oral hygiene behavior and evaluation. In conclusion, dental students provided the most accurate oral hygiene evaluations. Parents were stricter, and adolescents were more lenient. Among adolescents, longer brushing time was weakly associated with more accurate evaluations, and plaque disclosing agents enhanced evaluation accuracy.

Purpose:To analyze potential associations of anisometropia with ocular, systemic, and genetic factors in the general population in Germany. Methods:The Gutenberg Health Study is a population-based cohort study from Mainz, Germany, including 15,010 participants aged 35 to 74 years. We included 13,307 phakic participants with objective refraction; 8512 participants had axial length (AL) measurements. Anisometropia was defined by difference of the spherical equivalent refraction. Further intereye differences in AL and corneal power were evaluated. A multivariable logistic and quantile regression analysis and a genome-wide association study (GWAS) on anisometropia, intereye difference in AL, and corneal power were conducted. Results:Prevalence of anisometropia of ≥1 diopters (D) was 14.64% (95% confidence interval [CI], 14.04%-15.25%) and of ≥2 D 4.94% (95% CI, 4.58%-5.32%). The median AL difference between both eyes was 0.12 mm (range, 0-8.11 mm). With increasing myopia and hyperopia, there was a V-shaped increase in anisometropia with minimal anisometropia at 0 D. Age (odds ratio [OR], 1.01; 95% CI, 1.01-1.02; P < 0.001) and years of education (OR, 1.06; 95% CI, 1.03-1.08; P < 0.001) were associated with anisometropia of ≥1 D. Female sex was inversely associated with hyperopic anisometropia of ≥1 D (OR, 0.77; 95% CI, 0.62-0.96; P = 0.02). Body height, diabetes, and body mass index did not show an association. GWAS on intereye difference in AL revealed a significant (P < 5 × 10-8) association of 10 single nucleotide polymorphisms at the intron of DNAH5. Conclusions:Higher refractive error is associated with an increased risk for anisometropia. Myopic anisometropia was associated with years of education. The intereye difference in AL was associated with years of education and body height. This study identified a single genomic locus at the intron of DNAH5 to be associated with intereye differences in AL.

INTRODUCTION:Reliable continuous non-invasive blood pressure monitoring technology should support clinicians to maintain blood pressure within appropriate limits peri-operatively. Previous studies have shown conflicting results regarding measurement accuracy. METHODS:This systematic review and six meta-analyses evaluated the accuracy and precision of non-invasive continuous arterial blood pressure measurement technologies (volume clamp technology, applanation tonometry and photoplethysmography) compared with invasive arterial measurement in adults. We analysed pooled bias (mean difference between non-invasive and invasive measurement), standard deviation and limits of agreement. In each meta-analysis, mean arterial pressure (MAP), systolic blood pressure (SBP) and diastolic blood pressure (DBP) were analysed separately. Acceptability was defined according to Association for the Advancement of Medical Instrumentation® (AAMI) criteria. RESULTS:Sixty-five studies were included: two meta-analyses for volume clamp technology (ClearSight™, CNAP™); three meta-analyses for applanation tonometry (T-Line™, Vasotrac™ and N-CAT™); and one meta-analysis for photoplethysmography technology. For volume clamp technologies, none met AAMI criteria for bias and SD in relation to MAP, SBP and DBP. T-Line, Vasotrac and N-CAT met the AAMI criteria for bias for MAP (2.53 mmHg, 0.36 mmHg, -0.37 mmHg), SBP (-0.07 mmHg, 1.20 mmHg, -3.68 mmHg) and DBP (3.09 mmHg, 1.09 mmHg, 0.84 mmHg), respectively. In terms of standard deviation, only N-CAT (MAP 6.97 mmHg, SBP 7.14, mmHg, DBP 6.55 mmHg) met AAMI criteria for all blood pressure parameters. Photoplethysmography technology met AAMI criteria for bias (MAP -0.09 mmHg, SBP 0.49 mmHg, DBP -0.26 mmHg) and standard deviation (MAP 6.86 mmHg, DBP 6.38 mmHg). DISCUSSION:Overall, the AAMI criteria for bias and SD were not fulfilled for most of the devices tested and wide limits of agreement are of concern. One applanation tonometry device (N-CAT) shows promise. Clinicians should be aware of the lack of interchangeability with invasive blood pressure management.

BACKGROUND AND OBJECTIVES:Given the increasing incidence of cutaneous neoplasms, the nationwide skin cancer screening program was implemented in Germany in 2008. However, there are few studies evaluating its effectiveness. The aim of this analysis was to assess factors influencing participation and outcomes of skin cancer screening within the cohort of the Gutenberg Health Study (GHS). PATIENTS AND METHODS:The GHS is a retrospective cohort study conducted at the University Medical Center Mainz since 2007. Initially, 15,010 participants aged 35-74 years were recruited, with later inclusion of younger and older individuals. Data were collected through interviews on skin cancer screening participation and linked to participant-specific information such as cancer history and occupational background. RESULTS:In the GHS cohort, the participation rate in skin cancer screening was 62.1% (3,383 out of 5,452). Occupational UV exposure was associated with lower screening participation, whereas a history of cancer correlated with higher participation. Dermatologists were the preferred screening providers and demonstrated higher malignancy detection rates compared to general practitioners (36.7% compared to 20%). CONCLUSIONS:The participation rate in skin cancer screening within the GHS cohort was substantially higher than national averages. Nevertheless, risk-prone populations with outdoor occupations are currently not adequately reached by the screening program. Improved education and targeted interventions for high-risk groups are needed.

We develop blinded sample size re-estimation strategies for McNemar's test based on paired binary primary and secondary short-term surrogate endpoints. The development is motivated by a prospective randomized clinical trial on childhood glaucoma. A conditional power expression for McNemar's test given the primary endpoint at an interim analysis is derived and complemented by a sample size re-estimation rule. We show that this procedure preserves the type I error rate while allowing the second-stage sample size to be chosen to attain a prespecified target power. In the case where for some patients only a short-term surrogate endpoint is available at interim, we introduce a surrogate-based re-estimation approach that conditions on all possible numbers of primary-endpoint discordant pairs using transition rates from the surrogate to the primary outcome. We show how these transition rates can be estimated from data on a subsample for which both surrogate and primary endpoint are available. We derive the resulting surrogate endpoint-based conditional power and sample size rule and illustrate their use with the example of the motivating trial.

Amblyopia and strabismus are associated with a reduced health-related quality of life in children. This study aimed to investigate whether there is a relationship between amblyopia or strabismus and mental distress (depression, anxiety disorder), as well as differences in psychosocial characteristics. The Gutenberg Health Study is a population-based cohort study in Mainz, Germany, with 15,010 participants aged 35–74. The prevalence of depression and anxiety, and the presence of psychosocial characteristics were examined in individuals with and without strabismus or amblyopia. Logistic regression analyses were conducted to calculate associations. 14,431 individuals were included in the analysis for strabismus, of which 355 had a squint. The socioeconomic status was lower in individuals with strabismus (12.0 vs. 13.0, p = 0.01), and a higher percentage had a secondary school diploma (43.1

Background/Objectives: This prospective study aims to assess the clinical outcomes of the AutoCart™ technique for the treatment of medial osteochondral lesions of the talus (OLT). Methods: 29 consecutive patients treated for medial OLT were included. Demographic characteristics and preoperative imaging (MRI and CT) were reviewed, and patient-reported outcome measures (PROMs)-including a Visual Analog Pain Scale (VAS), Foot Function Index (FFI), Foot and Ankle Ability Measure (FAAM), and the Veterans RAND 12-Item Health Survey (VR-12)-were assessed preoperatively and at 6 and 12 months post-treatment. Results: In the cohort, 14 (48%) were female, 13 (45%) were male, and 2 (7%) did not disclose their gender. Median age was 35.5 years (interquartile range: 23.0-49.5). Mean defect size was 121.95 ± 84.46 mm2. Three patients were treated entirely arthroscopically, while 26 patients underwent medial malleolar osteotomy with cancellous bone grafting from the calcaneus for cartilage fragment placement. At one-year follow-up, there were significant improvements in pain and functional outcomes. The VAS score showed a mean reduction of 1.3 points (95% CI: -2.6 to -0.1; p = 0.036). Strong improvement was observed in the FFI, with a mean reduction of 13.3 points (95% CI: -21.0 to -5.6; p = 0.001). The FAAM Sports subscale showed a significant increase of 18.6 points (95% CI: 7.0 to 30.1; p = 0.002). Conclusions: Patients demonstrate clinical improvement after minced cartilage implantation with the AutoCart™ technique. These findings suggest that the minced cartilage procedure is a viable treatment option for medial OLTs, though further studies are needed to assess long-term efficacy.

Background & Aims: Immunotherapy with atezolizumab and bevacizumab (a + b) has improved the prognosis of patients with unresectable hepatocellular carcinoma (HCC). However, the outcome for individual patients is highly variable. This study aimed to (i) develop and validate a prognostic prediction model to estimate individual prognosis and (ii) compare it with established models. Methods: In this multicenter retrospective study, patients with HCC undergoing first-line immunotherapy with a + b from 24 centers (Europe, USA) were included. Statistical analysis and reporting followed the TRIPOD guidelines. The primary objective was overall survival (OS). A Cox model was developed and externally validated. Results: In total, 683 patients were included (training: 526, validation: 157). The C-reactive protein, albumin, bilirubin, lymphocytes, ECOG performance status, and extrahepatic spread (CABLE score) remained significantly associated with OS in Cox regression analysis. In the training set, the CABLE score had a higher discriminatory accuracy relative to ALBI, EZ-ALBI, mALBI, CRAFITY, PNI, NLR, PLR, and GPS (time-dependent AUC 0.79 and C-index 0.75 (95% CI 0.71-0.78) at 12 months). In the external validation set, the discriminatory performance of the CABLE score was comparable to ALBI, EZ-ALBI, and mALBI, but on average higher than PNI, CRAFITY, NLR, PLR, and GPS. In patients with Child-Pugh A, the CABLE score outperformed ALBI, EZ-ALBI, and mALBI in the first 9 months. We provide a web-based calculator for the CABLE score to allow estimation of individual prognosis for these patients (http://shiny.imbei.uni-mainz.de:3838/CABLE_Score/). Conclusions: The CABLE score shows good discriminatory performance in assessing the individual prognosis of patients undergoing first-line immunotherapy with a + b. Further validation studies are needed to investigate its performance compared with the ALBI score, in particular in subgroup analysis. (c) 2024 The Author(s). Published by Elsevier B.V. on behalf of European Association for the Study of the Liver (EASL). This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).

Background Post-COVID syndrome (PCS) affects up to 43% of all SARS-CoV-2-infected persons and describes ongoing symptoms months after the acute infection. Despite the large number of affected people, there is still very little evidence about therapeutic options. Some studies suggest at least partially a role of autoantibody-mediated autoimmunity. Immunoadsorption is an extracorporeal therapy to remove circulating antibodies which is used successfully in several autoimmune diseases. We conceived the IAMPOCO trial to evaluate the therapeutic effect of immunoadsorption in patients with PCS. Methods IAMPOCO is a single-center randomized sham-controlled trial with a crossover design which will enroll 40 participants with PCS and a symptom severity of at least 2 on post-COVID functional scale. All participants will undergo 5 immunoadsorption treatments and after a washout period of 8 weeks 5 sham treatments or vice versa. Which modality is conducted first will be randomized. Patients but not providers of therapy are blinded for which modality is conducted. Primary outcome is the efficacy of IA to the severity of PCS measured by the change of several symptom scores and hand grip strength. Secondary outcomes are the frequency of adverse events and the prevalence of relevant autoantibodies in participants with PCS as well as the concentration of autoantibodies before and after therapy and sham treatment. Discussion The trial addresses the lack of evidence for treatment options in PCS. By using a crossover design and including a sham treatment arm, the study aims to compare the effects of immunoadsorption and sham therapy within the same patients. The trial also benefits from recruiting participants from a cohort study on PCS prevalence, ensuring a thorough evaluation of symptoms. Objective assessments of symptoms are challenging due to their subjective nature, but various scoring systems and tests are being utilized. Despite the lack of data from RCTs, the results of this study have the potential to significantly improve PCS therapy and support evidence-based treatment decisions. Trial registration ClinicalTrials.gov NCT05841498. Registered on May 3, 2023.

AIMS:Childhood cancer is a risk factor for cardiovascular diseases in later life. Retinal examination allows to non-invasively observe the vasculature of an end-organ. We observe alterations in long-term childhood cancer survivors (CCS). METHODS:In the Cardiac and Vascular Late Sequelae in Long-Term Survivors of Childhood Cancer-Study, 1002 CCS (23-48 years) having neoplasia prior to 15 years of age were prospectively enrolled in a general and ophthalmologic examination including fundus photography. Central retinal vessel equivalents (arterial: CRAE; venous CRVE) were measured and linear regression analysis was computed to compare CCS to controls from the population-based Gutenberg Health Study (GHS) with adjustment for potential cardiovascular and ophthalmological confounders. Differences in cancer types and treatments were explored. RESULTS:For 837 CCS (45.3% female), CRAE and CRVE were conducted. Both were smaller in CCS previously having leukaemia, central nervous system tumour, neuroblastoma, renal tumour, malignant bone tumour, soft tissue sarcoma and germ cell tumour than in GHS controls. No difference was found for CCS with prior lymphoma. Previous radiotherapy of head or neck was associated with a smaller CRVE. Higher mean arterial blood pressure and intake of antihypertensive medication were associated with smaller CRAE. CONCLUSIONS:Retinal vasculature is altered in CCS leading to smaller retinal arteries and veins. Our finding indicates that childhood cancer and its treatment leads to systemic alterations of the microcirculation on both branches of the vasculature system. While the retinal venous vasculature is altered by radiotherapy, the lower vessel width of the arterial branch is associated with arterial hypertension.

Introduction: Analysis of administrative data has helped to determine hospitalization costs related to acute pulmonary embolism (PE) in several countries, but estimating long-term costs of patient care after discharge is a more challenging task. Aims: To determine the direct annual costs related to the care of PE survivors based on data from a longitudinal cohort study performed at 17 German large-volume hospitals. Methods: The Follow-up of Acute Pulmonary Embolism (FOCUS) study enrolled unselected patients with acute PE. In addition to a structured ambulatory follow-up (FU) program (Figure) , we prospectively recorded duration and type of anticoagulation and the main and accompanying causes of all rehospitalizations during the first year of FU. Annual per-patient costs of post-PE care were calculated in 2022 euro (є) and converted to US$ adjusting for purchase parity power. Results: A total of 1,017 patients (45% women; median age 64 years [IQR, 52-74]) were included. Average costs of scheduled ambulatory FU visits and tests were estimated at є136.37 ($189.40) per patient; costs of oral anticoagulation after hospital discharge for the index event amounted to є827.72 ($1,149.61). The annual all-cause hospitalization rate was 31.96% (95% CI, 28.0-35.91%); the Table shows the primary indications and mean hospital costs (overall, and per indication). Of the є1,104.48 ($1,534.0) average rehospitalization costs per patient, 8.9% were related to recurrent thrombosis/PE or bleeding. Conclusions: Our results, derived from the population of a prospective multicenter study, help to dissect the direct annual costs of chronic post-PE care and may inform ambulatory care programs.

Precise segmental spinal analysis during gait has various implications for clinical use and basic research. Here, we report the use of Surface Topography (ST) to analyze three-dimensional spinal segment movements, in combination with foot pressure measuring, to describe individual vertebral bodies’ motion relative to specific phases of gait. Using Statistical Analysis System (SAS) scripts, single files were merged into one raw data table and were used to generate a standardized gait cycle (SGC) for each measurement, including all measured gait cycles for each individual patient, with a spline function to obtain smooth curve progressions. Graph templates from Statistical Package for the Social Sciences create detailed visualizations of the SGCs. Previously obtained measurements from healthy participants were used to demonstrate possible applications of our method. An impressive inter-individual variability as well as intra-individual consistency of spinal motion is shown. The transformation into an SGC facilitates intra- and inter-individual comparisons for qualitative and quantitative analyses. In future studies, we want to use this method to distinguish between physiologic and pathologic spinal motion. Artificial intelligence-based analysis can facilitate this process. All tools and visualizations used are freely available in repositories to enable the replication and validation of our findings.

Background Early diagnosis of chronic kidney disease (CKD) is essential to slow progression and delay or prevent dialysis. However, in the absence of specific symptoms, patients and physicians may remain unaware of the disease for a long period. Here we present an analysis from the Gutenberg Health Study, a prospective longitudinal cohort study, to estimate the prevalence of CKD indicators in the population. Methods A representative sample of 10 125 individuals underwent extensive medical testing at baseline; 9331 were tested again after 5 years. The estimated glomerular filtration rate (eGFR) was calculated using the Chronic Kidney Disease Epidemiology Collaboration formula with serum creatinine. Urinary albumin:creatinine ratios (UACRs) were determined from spot urine samples. Results At baseline, 2.5% of subjects had decreased eGFR (<60 ml/min/1.73 m(2)), 10.4% had increased albuminuria (UACR >30 mg/g) and 1.0% had both. Within 5 years, the incidence of new-onset decreased eGFR was 3.4%, the incidence of new-onset increased albuminuria was 6.9% and 1.4% had both new-onset decreased eGFR and increased albuminuria. Most importantly, 6.8% of all subjects and 3.2% of subjects without hypertension, diabetes or known kidney disease had chronic increased albuminuria, consistent with the presence of CKD. Conclusions This is the first study to report the longitudinal prevalence of CKD in the population. Chronic increased albuminuria, a sensitive marker of CKD, is highly prevalent in the German population even in the absence of risk factors for kidney disease.

Purpose:To compare the peripapillary retinal nerve fiber layer (pRNFL) thickness of large optic discs in children (LOD-C) with normal sized optic discs in children (NOD-C) and large optic discs in adults (LOD-A). Methods:We included 127 eyes per group (n = 381). Optic discs were considered large if the Bruch's membrane opening (BMO) area was ≥2.5 mm2. pRNFL thickness and minimal rim width (BMO-MRW) were compared between the pediatric groups and the large optic disc groups. Results:The mean global pRNFL thickness (3.5-mm circle) was 100.2 ± 12.1 µm for LOD-C, 95.9 ± 11.7 µm for NOD-C, and 97.7 ± 10.5 µm for LOD-A. It was significantly thicker in LOD-C compared with NOD-C; the difference decreased toward the periphery. The mean global BMO-MRW was 280.0 ± 41.1 µm for LOD-C, 320.7 ± 10.5 µm for NOD-C, and 252.9 ± 45.8 µm for LOD-A. It was significantly thinner in LOD-C compared with NOD-C, and significantly thicker in LOD-C compared with LOD-A. pRNFL and BMO area showed a positive correlation which was higher if BMO area was >2.8 mm2, BMO-MRW and BMO are showed a negative correlation which was higher if BMO area was <1.9 mm2. Conclusions:RNFL and BMO-MRW of pediatric optic discs with BMO area <1.9 mm2 and >2.8 mm2 should be interpreted with caution, because they seem to be strongly influenced by optic disc size. Translational Relevance:The novel thresholds for small and LOD-C will help to account for the effects of disc status on RNFL and MRW. They will furthermore help clinicians to better diagnose children with suspicious discs for glaucoma.

Background: Dysregulated aldosterone is a modulator for the development and progression of cardio-renal-metabolic disease. Aim: This study aimed to investigate the prognostic value of aldosterone plasma concentration in relation to incident cardiovascular disease (CVD) and mortality in a population-based cohort. Methods: Participants from the population-based Gutenberg Health Study, a prospective cohort in Western Germany, underwent deep clinical phenotyping including venous blood sampling under standardized conditions. Quantification of baseline aldosterone concentration was performed using a chemiluminescent immunoassay (DiaSorin, Dietzenbach, Germany). Incident CVD was defined as the composite endpoint of incident coronary artery disease, atrial fibrillation, stroke, myocardial infarction and cardiac death. Mortality was assessed through regular verification of vital status via registration offices and death certificates from the mortality registry. Aldosterone concentrations were stratified by quartiles. Cox regression adjusted for age and sex was used to assess the association between aldosterone concentration and clinical outcomes. Based on an observed nonlinear U-shaped relationship, the lowest (Q1) and highest (Q4) quartiles were each compared against the middle quartiles (Q2-Q3). Results: The analysis sample included n=14,756 individuals with aldosterone measurements with a mean±SD age of 55.0±11.1 years, of whom 49.3% were women. The median (interquartile range) plasma concentration of aldosterone was 7.51 ng/dL (5.62/10.10). Follow-up time for all-cause death was 15 years (n events=1,753), for cardiac death 10 years (n events=716) and for incident CVD 5 years (n events=759). Compared to the middle quartiles (Q2-Q3) of aldosterone, individuals in the lowest quartile (Q1) had a higher risk of all-cause death (hazard ratio [HR] 1.16, 95% confidence interval [CI] 1.03; 1.30, p=0.012), while the associations with cardiac death (HR 1.21, 95% CI 0.87; 1.68, p=0.26) and incident CVD (HR 0.96, 95% CI 0.81; 1.15, p=0.67) were not statistically significant. In contrast, those in the highest quartile (Q4) showed an increased risk of all-cause death (HR 1.46, 95% CI 1.31; 1.64, p<0.0001), cardiac death (HR 1.65, 95% CI 1.22; 2.24, p=0.0012), and incident CVD (HR 1.29, 95% CI 1.09; 1.53, p=0.004). Conclusion: In this large population-based cohort, dysregulated plasma aldosterone was associated with an increased risk of mortality, cardiac death, and incident CVD.