Topographic Clinical Insights From Deep Learning-Based Geographic Atrophy Progression Prediction.

Purpose: To explore the contributions of fundus autofluorescence (FAF) topographic imaging features to the performance of convolutional neural network-based deep learning (DL) algorithms in predicting geographic atrophy (GA) growth rate.

Methods: Retrospective study with data from study eyes from three clinical trials (NCT02247479, NCT02247531, NCT02479386) in GA. The algorithm was initially trained with full FAF images, and its performance was considered benchmark.

Geographic Atrophy Segmentation Using Multimodal Deep Learning.

Purpose: To examine deep learning (DL)-based methods for accurate segmentation of geographic atrophy (GA) lesions using fundus autofluorescence (FAF) and near-infrared (NIR) images.

Methods: This retrospective analysis utilized imaging data from study eyes of patients enrolled in Proxima A and B (NCT02479386; NCT02399072) natural history studies of GA. Two multimodal DL networks (UNet and YNet) were used to automatically segment GA lesions on FAF; segmentation accuracy was compared with annotations by experienced graders.

Identifying clinically useful biomarkers in neurodegenerative disease through a collaborative approach: the NeuroToolKit.

Background: Alzheimer's disease (AD) is a complex and heterogeneous disease, which requires reliable biomarkers for diagnosis and monitoring disease activity. Preanalytical protocol and technical variability associated with biomarker immunoassays makes comparability of biomarker data across multiple cohorts difficult. This study aimed to compare cerebrospinal fluid (CSF) biomarker results across independent cohorts, including participants spanning the AD continuum.

Clinical performance and robustness evaluation of plasma amyloid-β prescreening.

Introduction: Further evidence is needed to support the use of plasma amyloid β (Aβ) biomarkers as Alzheimer's disease prescreening tools. This study evaluated the clinical performance and robustness of plasma Aβ /Aβ for amyloid positivity prescreening.

Methods: Data were collected from 333 BioFINDER and 121 Alzheimer's Disease Neuroimaging Initiative study participants.

Evaluating the Safety and Efficacy of Crenezumab vs Placebo in Adults With Early Alzheimer Disease: Two Phase 3 Randomized Placebo-Controlled Trials.

Importance: Alzheimer disease (AD), a neurodegenerative disease characterized by β-amyloid plaques and τ tangles in the brain, represents an unmet medical need with no fully approved therapeutics to modify disease progression.

Objective: To investigate the safety and efficacy of crenezumab, a humanized monoclonal immunoglobulin G4 antibody targeting β-amyloid oligomers, in participants with prodromal to mild (early) AD.

Design, Setting, And Participants: Two phase 3 multicenter randomized double-blind placebo-controlled parallel-group efficacy and safety studies of crenezumab in participants with early AD, CREAD and CREAD2, were initiated in 2016 and 2017, respectively, and were designed to evaluate the efficacy and safety of crenezumab in participants with early AD.

Deep Learning to Predict Geographic Atrophy Area and Growth Rate from Multimodal Imaging.

Objective: To develop deep learning models for annualized geographic atrophy (GA) growth rate prediction using fundus autofluorescence (FAF) images and spectral-domain OCT volumes from baseline visits, which can be used for prognostic covariate adjustment to increase power of clinical trials.

Design: This retrospective analysis estimated GA growth rate as the slope of a linear fit on all available measurements of lesion area over a 2-year period. Three multitask deep learning models-FAF-only, OCT-only, and multimodal (FAF and OCT)-were developed to predict concurrent GA area and annualized growth rate.

Target engagement in an alzheimer trial: Crenezumab lowers amyloid β oligomers in cerebrospinal fluid.

Objective: Oligomeric forms of amyloid β protein (oAβ) are believed to be principally responsible for neurotoxicity in Alzheimer disease (AD), but it is not known whether anti-Aβ antibodies are capable of lowering oAβ levels in humans.

Methods: We developed an ultrasensitive immunoassay and used it to measure oAβ in cerebrospinal fluid (CSF) from 104 AD subjects participating in the ABBY and BLAZE phase 2 trials of the anti-Aβ antibody crenezumab. Patients received subcutaneous (SC) crenezumab (300mg) or placebo every 2 weeks, or intravenous (IV) crenezumab (15mg/kg) or placebo every 4 weeks for 68 weeks.

Amyloid positron emission tomography and cerebrospinal fluid results from a crenezumab anti-amyloid-beta antibody double-blind, placebo-controlled, randomized phase II study in mild-to-moderate Alzheimer's disease (BLAZE).

Background: We investigated the effect of crenezumab, a humanized anti-amyloid-beta (Aβ) immunoglobulin (Ig)G4 monoclonal antibody, on biomarkers of amyloid pathology, neurodegeneration, and disease progression in patients with mild-to-moderate Alzheimer's disease (AD).

Methods: This double-blind, placebo-controlled, randomized phase II study enrolled patients with mild-to-moderate AD and a Mini-Mental State Examination (MMSE) score of 18-26. In part 1 of the study, patients were 2:1 randomized to receive low-dose subcutaneous (SC) 300 mg crenezumab every 2 weeks (q2w) or placebo for 68 weeks; in part 2, patients were 2:1 randomized to receive high-dose intravenous (IV) 15 mg/kg crenezumab every 4 weeks (q4w) or placebo for 68 weeks.

ABBY: A phase 2 randomized trial of crenezumab in mild to moderate Alzheimer disease.

Objective: To evaluate the safety and efficacy of crenezumab in patients with mild to moderate Alzheimer disease (AD).

Methods: In this phase 2 trial, 431 patients with mild to moderate AD 50 to 80 years of age were randomized 2:1 (crenezumab:placebo). Patients received low-dose subcutaneous crenezumab 300 mg or placebo every 2 weeks (n = 184) or high-dose intravenous crenezumab 15 mg/kg or placebo every 4 weeks (n = 247) for 68 weeks.

CSF biomarkers of Alzheimer's disease concord with amyloid-β PET and predict clinical progression: A study of fully automated immunoassays in BioFINDER and ADNI cohorts.

Introduction: We studied whether fully automated Elecsys cerebrospinal fluid (CSF) immunoassay results were concordant with positron emission tomography (PET) and predicted clinical progression, even with cutoffs established in an independent cohort.

Methods: Cutoffs for Elecsys amyloid-β (Aβ), total tau/Aβ(1-42), and phosphorylated tau/Aβ(1-42) were defined against [F]flutemetamol PET in Swedish BioFINDER (n = 277) and validated against [F]florbetapir PET in Alzheimer's Disease Neuroimaging Initiative (n = 646). Clinical progression in patients with mild cognitive impairment (n = 619) was studied.

Technical performance of a novel, fully automated electrochemiluminescence immunoassay for the quantitation of β-amyloid (1-42) in human cerebrospinal fluid.

Introduction: Available assays for quantitation of the Alzheimer's disease (AD) biomarker amyloid-beta 1-42 (Aβ [1-42]) in cerebrospinal fluid demonstrate significant variability and lack of standardization to reference measurement procedures (RMPs). We report analytical performance data for the novel Elecsys β-amyloid (1-42) assay (Roche Diagnostics).

Methods: Lot-to-lot comparability was tested using method comparison.

Blood-sampling collection prior to surgery may have a significant influence upon biomarker concentrations measured.

Background: Biomarkers can be subtle tools to aid the diagnosis, prognosis and monitoring of therapy and disease progression. The validation of biomarkers is a cumbersome process involving many steps. Serum samples from lung cancer patients were collected in the framework of a larger study for evaluation of biomarkers for early detection of lung cancer.

Upregulation of Periostin and Reactive Stroma Is Associated with Primary Chemoresistance and Predicts Clinical Outcomes in Epithelial Ovarian Cancer.

Purpose: Up to one third of ovarian cancer patients are intrinsically resistant to platinum-based treatment. However, predictive and therapeutic strategies are lacking due to a poor understanding of the underlying molecular mechanisms. This study aimed to identify key molecular characteristics that are associated with primary chemoresistance in epithelial ovarian cancers.

IL-6 pathway-driven investigation of response to IL-6 receptor inhibition in rheumatoid arthritis.

Objectives: To determine whether heterogeneity in interleukin-6 (IL-6), IL-6 receptor and other components of the IL-6 signalling pathway/network, at the gene, transcript and protein levels, correlate with disease activity in patients with rheumatoid arthritis (RA) and with clinical response to tocilizumab.

Design: Biomarker samples and clinical data for five phase 3 trials of tocilizumab were analysed using serum (3751 samples), genotype (927 samples) and transcript (217 samples) analyses. Linear regression was then used to assess the association between these markers and either baseline disease activity or treatment response.

A PAUC-based estimation technique for disease classification and biomarker selection.

The partial area under the receiver operating characteristic curve (PAUC) is a well-established performance measure to evaluate biomarker combinations for disease classification. Because the PAUC is defined as the area under the ROC curve within a restricted interval of false positive rates, it enables practitioners to quantify sensitivity rates within pre-specified specificity ranges. This issue is of considerable importance for the development of medical screening tests.

Predictive factors of mortality after PEG insertion: guidance for clinical practice.

Background: Percutaneous endoscopic gastrostomy (PEG) is considered the preferred route for long-term enteral feeding. The aim of this study was to determine predictors of an increased mortality risk after PEG insertion.

Methods: A retrospective study was conducted during a 13-year period in the gastroenterology department of Erlangen University Hospital.

Alterations of taste perception in Crohn's disease and their dependency on disease activity and nutritional behavior.

Background: The pathogenesis of Crohn's disease (CD) is unknown. Besides immunoregulatory, genetic and environmental aspects, a nutritional impact is also encountered. Whether taste perception exerts any influence on an increased consumption of carbohydrates is unknown.

Risk factors associated with adverse drug reactions following hospital admission: a prospective analysis of 907 patients in two German university hospitals.

Background: Since the 1970s, studies have examined potential risk factors associated with adverse drug reactions (ADRs) in a variety of settings. However, no pharmacoepidemiological study exists that incorporates clinical and laboratory parameters in a multiple regression model in order to consider predictors for ADRs.

Objectives: To characterize risk factors associated with ADRs in patients admitted to university hospital departments of internal medicine.

Potential of ultrasound diagnosis for parotid tumors: analysis of qualitative and quantitative parameters.

Objective: Histology of parotid tumors determines the extent of surgery. The aim was to test ultrasound (US) contrast enhancer-kinetics to identify histologic entities, possibly being superior to qualitative morphological parameters.

Study Design: In a cross-sectional assessment of ultrasound diagnosis, the subjective US-classification was compared with contrast analysis with histology as gold standard.

The value of dynamic MRI studies in parotid tumors.

Rationale And Objectives: To evaluate the ability of dynamic contrast-enhanced magnetic resonance imaging (MRI) to differentiate several tumor entities of the parotid gland in a prospective clinical trial.

Materials And Methods: A total of 112 patients with parotid tumors were examined with dynamic contrast-enhanced 1.5 T MRI.

Generalized approaches to partitioning the attributable risk of interacting risk factors can remedy existing pitfalls.

Objective: To clarify the properties of different approaches to estimate the contribution of single-risk factors to the disease load in a population.

Study Design And Setting: Three methods of partitioning attributable risks are reviewed and two additional procedures as modifications of the existing algorithms are introduced. Basis properties of the approaches are outlined in the simplest setting with two exposure variables.

Neck lymph nodes: prediction by computer-assisted contrast medium analysis?

Several criteria in B-scan and colour-coded Doppler ultrasound have been shown to discriminate malignant transformation of cervical lymph nodes. All these parameters tend to be operator dependent. We describe the first use of computer-assisted analysis of contrast-enhanced ultrasound images evaluating cervical lymphadenopathy in differentiation between benign and malignant lesions.

Hepatitis B vaccination status among healthy adults in Germany.

Objectives: The hepatitis B vaccination policy in Germany was intensified by the implementation of hepatitis B vaccination for adolescents in the vaccination calendar in 1995. To investigate the effect of this measure on the hepatitis B vaccination coverage of healthy adults, we analysed the hepatitis B vaccination status of blood donors. Furthermore, the reasons for vaccination and the relationship between vaccination status and age, sex, and current profession were studied.