Spatial organization of B lymphocytes and prognosis prediction in patients with gastric cancer.

Background: Within the tumor microenvironment (TME), the association of B lymphocytes (B cells) with prognosis and therapy response in gastric cancer (GC) remains poorly characterized. We investigated the predictive and prognostic value of B cells, including their spatial organization within the TME, in one of the largest multi-cohort studies to date.

Methods: Using CD20 immunohistochemistry, we evaluated B cell density in resection specimens from 977 patients with resectable GC across three cohorts, including the randomized phase III Korean CLASSIC trial.

HER2 quantitative continuous scoring for accurate patient selection in HER2 negative trastuzumab deruxtecan treated breast cancer.

Many targeted cancer therapies rely on biomarkers assessed by scoring of immunohistochemically (IHC)-stained tissue, which is subjective, semiquantitative, and does not account for expression heterogeneity. We describe an image analysis-based method for quantitative continuous scoring (QCS) of digital whole-slide images acquired from baseline human epidermal growth factor receptor 2 (HER2) IHC-stained breast cancer tissue. Candidate signatures for patient stratification using QCS of HER2 expression on subcellular compartments were identified, addressing the spatial distribution of tumor cells and tumor-infiltrating lymphocytes.

Spatial heterogeneity of cancer associated protein expression in immunohistochemically stained images as an improved prognostic biomarker.

The identification of new tumor biomarkers for patient stratification before therapy, for monitoring of disease progression, and for characterization of tumor biology plays a crucial role in cancer research. The status of these biomarkers is mostly scored manually by a pathologist and such scores typically, do not consider the spatial heterogeneity of the protein's expression in the tissue. Using advanced image analysis methods, marker expression can be determined quantitatively with high accuracy and reproducibility on a per-cell level.

Quality of life, infection control, and complication rates using a novel custom-made articulating hip spacer during two-stage revision for periprosthetic joint infection.

Introduction: Two-stage revision remains the gold standard treatment for most chronically infected and complex total hip arthroplasty infections. To improve patient outcome and reduce complication rates, we have developed a novel custom-made articulating hip spacer technique and present our short-term results.

Materials And Methods: Between November 2017 and November 2019, 27 patients (mean age 70 years) underwent two-stage revision for periprosthetic joint infection of the hip using the articulating spacer design described here.

Domain Adaptation-Based Deep Learning for Automated Tumor Cell (TC) Scoring and Survival Analysis on PD-L1 Stained Tissue Images.

We report the ability of two deep learning-based decision systems to stratify non-small cell lung cancer (NSCLC) patients treated with checkpoint inhibitor therapy into two distinct survival groups. Both systems analyze functional and morphological properties of epithelial regions in digital histopathology whole slide images stained with the SP263 PD-L1 antibody. The first system learns to replicate the pathologist assessment of the Tumor Cell (TC) score with a cut-point for positivity at 25% for patient stratification.

Assessment of Immunological Features in Muscle-Invasive Bladder Cancer Prognosis Using Ensemble Learning.

The clinical staging and prognosis of muscle-invasive bladder cancer (MIBC) routinely includes the assessment of patient tissue samples by a pathologist. Recent studies corroborate the importance of image analysis in identifying and quantifying immunological markers from tissue samples that can provide further insight into patient prognosis. In this paper, we apply multiplex immunofluorescence to MIBC tissue sections to capture whole-slide images and quantify potential prognostic markers related to lymphocytes, macrophages, tumour buds, and PD-L1.

[Changes of sex ratio and prevalence in transgender teenagers over the past 15 years].

Changes of sex ratio and prevalence in transgender teenagers over the past 15 years Evaluation of authors' 1434 expert opinions from 2005-2019 on transgender applicants (420 younger than 20 years old) for legal change of name and gender according to German "Law on Transsexuality" showed (1) in teenage applicants substantial changes of sex ratio from 2:1 to 10:1 in favour of transmales; (2) while prevalence of teenage transfemales during this period remained unchanged, prevalence of transmales rose significantly. According to our data, transgender teenagers are nowadays primarily natal females. Clinical and sociocultural aspects of these changes are discussed.

Hypothesis-free deep survival learning applied to the tumour microenvironment in gastric cancer.

The biological complexity reflected in histology images requires advanced approaches for unbiased prognostication. Machine learning and particularly deep learning methods are increasingly applied in the field of digital pathology. In this study, we propose new ways to predict risk for cancer-specific death from digital images of immunohistochemically (IHC) stained tissue microarrays (TMAs).

Automatic discovery of image-based signatures for ipilimumab response prediction in malignant melanoma.

In the context of precision medicine with immunotherapies there is an increasing need for companion diagnostic tests to identify potential therapy responders and avoid treatment coming along with severe adverse events for non-responders. Here, we present a retrospective case study to discover image-based signatures for developing a potential companion diagnostic test for ipilimumab (IPI) in malignant melanoma. Signature discovery is based on digital pathology and fully automatic quantitative image analysis using virtual multiplexing as well as machine learning and deep learning on whole-slide images.

Automated tumour budding quantification by machine learning augments TNM staging in muscle-invasive bladder cancer prognosis.

Tumour budding has been described as an independent prognostic feature in several tumour types. We report for the first time the relationship between tumour budding and survival evaluated in patients with muscle invasive bladder cancer. A machine learning-based methodology was applied to accurately quantify tumour buds across immunofluorescence labelled whole slide images from 100 muscle invasive bladder cancer patients.

Deep Semi Supervised Generative Learning for Automated Tumor Proportion Scoring on NSCLC Tissue Needle Biopsies.

The level of PD-L1 expression in immunohistochemistry (IHC) assays is a key biomarker for the identification of Non-Small-Cell-Lung-Cancer (NSCLC) patients that may respond to anti PD-1/PD-L1 treatments. The quantification of PD-L1 expression currently includes the visual estimation by a pathologist of the percentage (tumor proportional scoring or TPS) of tumor cells showing PD-L1 staining. Known challenges like differences in positivity estimation around clinically relevant cut-offs and sub-optimal quality of samples makes visual scoring tedious and subjective, yielding a scoring variability between pathologists.

Tissue Phenomics for prognostic biomarker discovery in low- and intermediate-risk prostate cancer.

Tissue Phenomics is the discipline of mining tissue images to identify patterns that are related to clinical outcome providing potential prognostic and predictive value. This involves the discovery process from assay development, image analysis, and data mining to the final interpretation and validation of the findings. Importantly, this process is not linear but allows backward steps and optimization loops over multiple sub-processes.

Repetitive use of levosimendan in advanced heart failure: need for stronger evidence in a field in dire need of a useful therapy.

Patients in the latest stages of heart failure are severely compromised, with poor quality of life and frequent hospitalizations. Heart transplantation and left ventricular assist device implantation are viable options only for a minority, and intermittent or continuous infusions of positive inotropes may be needed as a bridge therapy or as a symptomatic approach. In these settings, levosimendan has potential advantages over conventional inotropes (catecholamines and phosphodiesterase inhibitors), such as sustained effects after initial infusion, synergy with beta-blockers, and no increase in oxygen consumption.

The effect of a checklist on the quality of post-anaesthesia patient handover: a randomized controlled trial.

Objective: Patient handover is an important element of continuity, quality and safety in patient care. Handover without standardized protocols is prone to information loss and might be a possible danger to patient safety. Checklists are established methods that help to structure complex processes in other high-risk fields such as aviation.

Single-channel amplitude integrated EEG recording for the identification of epileptic seizures by nonexpert physicians in the adult acute care setting.

Objective: Although several studies have shown the potential of amplitude integrated electroencephalography (aEEG) in detecting neonatal seizures, no publications have evaluated the diagnostic use of aEEG for the detection of seizures in adult patients.

Methods: In this prospective blinded observational study, bifrontal single-channel electroencephalography (EEG) recordings were performed with a portable EEG monitor (CSM M3 ICU, Danmeter-Goalwick Holdings Limited, Odense, Denmark) during the out-of-hospital care of emergency cases. Four intensive care unit (ICU) physicians received training in the interpretation of aEEG recordings.

Single-channel electroencephalography of epileptic seizures in the out-of-hospital setting: an observational study.

Objectives: To evaluate whether single-channel electroencephalography (EEG) recording can be conducted in the out-of-hospital setting and whether it can be used to record electrographic signs of convulsive epileptic seizures.

Methods: This prospective observational feasibility study included patients who presented with a recent or ongoing epileptic seizure during out-of-hospital emergency treatment. Bifrontal single-channel EEG recordings were conducted by ambulance physicians throughout the initial treatment.

Comparison of the over-the-head, lateral and alternating positions during cardiopulmonary resuscitation performed by a single rescuer with a bag--valve--mask device.

Background: The 2005 guidelines for cardiopulmonary resuscitation (CPR) do not include a statement on performance of basic life support by a single healthcare professional using a bag-valve-mask device. Three positions are possible: chest compressions and ventilations from over the head of the casualty (over-the-head CPR), from the side of the casualty (lateral CPR), and chest compressions from the side and ventilations from over the head of the casualty (alternating CPR). The aim of this study was to compare CPR quality of these three positions.

Electroencephalography during out-of-hospital cardiopulmonary resuscitation.

Background: At the present time there is no parameter that can estimate the quality of cerebral perfusion and possible success of cerebral resuscitation during advanced cardiac life support (ACLS) efforts. In recent years, various attempts have been made to use electroencephalography (EEG)-based cerebral neuromonitoring to assess the effectiveness of cardiopulmonary resuscitation (CPR).

Objectives: The Cerebral State Monitor M3 (Danmeter A/S, Odense, Denmark) is a portable, single-channel EEG monitor that provides the user with different EEG-based parameters and the raw waveform EEG to measure cerebral activity.

Cognition Network Technology prototype of a CAD system for mammography to assist radiologists by finding similar cases in a reference database.

Purpose: We present a new approach for computer-aided detection and diagnosis in mammography based on Cognition Network Technology (CNT). Originally designed for image processing, CNT has been extended to also perform context- and knowledge-driven analysis of tabular data. For the first time using this technology, an application was created and evaluated for fully automatic searching of patient cases from a reference database of verified findings.

Histopathological, radiological and clinical aspects of the temporal assignment of scaphoid non-union.

Objective: The aim of this study was to evaluate the correlation between clinical, radiological and histopathological signs of scaphoid non-unions (SNU) with regard to the age of the fracture, primarily because this is relevant for therapy and compensation claims.

Materials And Methods: Thirty-eight patients with SNU underwent clinical and radiological examination of the wrist prior to surgery. Preoperative X-rays of the wrist were analysed using the scores of Herbert and Fisher, Filan and Herbert, Trojan and Jahna, Gupta as well as scaphoid non-union advanced collapse.

A comparison between over-the-head and standard cardiopulmonary resuscitation performed by two rescuers: a simulation study.

Background: In cardiopulmonary resuscitation (CPR) of a patient with an unsecured airway performed by two health care professionals, two methods are possible: 1) Standard CPR according to the guidelines, with one rescuer performing chest compressions from the side and the other rescuer performing ventilations from over the head of the patient. Additional tasks (like attaching the electrocardiogram and defibrillator) must be performed by the second rescuer during the time between ventilations. 2) Over-the-head CPR, with one rescuer performing chest compressions and ventilations from over the head and the other rescuer performing additional tasks.

Comparison and evaluation of methods for liver segmentation from CT datasets.

This paper presents a comparison study between 10 automatic and six interactive methods for liver segmentation from contrast-enhanced CT images. It is based on results from the "MICCAI 2007 Grand Challenge" workshop, where 16 teams evaluated their algorithms on a common database. A collection of 20 clinical images with reference segmentations was provided to train and tune algorithms in advance.

Novel heterocyclic thyromimetics. Part 2.

Novel heterocyclic thyromimetics are presented carrying carboxy-substituted benzofurans or sulfur containing heterocycles, as replacements for the amino acid side chain of T3. Potent agonists were identified in both series. SAR trends are examined and found to be mostly consistent with previously published thyromimetics.

Identification of sensory blockade by somatosensory and pain-induced evoked potentials.

Background: To date, the anesthesia-induced blockade of nociceptive inputs is insufficiently reflected by commercially available electroencephalographic depth-of-anesthesia monitors. The aim of the current study was to evaluate the potential of somatosensory (SSEP) and intracutaneous pain evoked (iSEP) potentials during remifentanil and propofol anesthesia as electroencephalographic indicators of the nociceptive blockade.

Methods: Ten healthy men were investigated in a double-blind crossover design during three sessions with remifentanil, propofol, and placebo administration.