GAN-based Virtual Re-Staining: A Promising Solution for Whole Slide Image Analysis

Histopathological cancer diagnosis is based on visual examination of stained tissue slides. Hematoxylin and eosin (H\&E) is a standard stain routinely employed worldwide. It is easy to acquire and cost effective, but cells and tissue components show low-contrast with varying tones of dark blue and pink, which makes difficult visual assessments, digital image analysis, and quantifications. These limitations can be overcome by IHC staining of target proteins of the tissue slide. IHC provides a selective, high-contrast imaging of cells and tissue components, but their use is largely limited by a significantly more complex laboratory processing and high cost. We proposed a conditional CycleGAN (cCGAN) network to transform the H\&E stained images into IHC stained images, facilitating virtual IHC staining on the same slide. This data-driven method requires only a limited amount of labelled data but will generate pixel level segmentation results. The proposed cCGAN model improves the original network \cite{zhu_unpaired_2017} by adding category conditions and introducing two structural loss functions, which realize a multi-subdomain translation and improve the translation accuracy as well. % need to give reasons here. Experiments demonstrate that the proposed model outperforms the original method in unpaired image translation with multi-subdomains. We also explore the potential of unpaired images to image translation method applied on other histology images related tasks with different staining techniques

Impact of the COVID-19 Lockdown on Ophthalmological Assistance in the Emergency Department at a Spanish Primary Level Hospital.

Purpose. To analyze the changes in ophthalmological emergencies during the COVID-19 pandemic lockdown at a Spanish primary level hospital. Methods. The number and type of emergencies attended in the emergency department of Hospital Universitario del Henares between March 10 and August 31, 2020 (COVID-19 cohort) were compared with the emergencies attended during the same period of 2019 (pre-COVID-19 cohort). Data on the diagnosis, patient age, and gender was retrospectively collected from the electronic medical records of the hospital. The different diagnoses were organized into “clusters,” which include those conditions that affect the same ocular tissue and that have similar clinical expression. Results. The number of ophthalmological emergencies during the study period was 841, compared to 1343 during the same month of 2019, which represents a reduction of 37.4%. The percentage reduction in each cluster was as follows: conjunctiva (−65.4%), cornea (−35.8%), uveitis (−3.6%), eyelid and orbital and lacrimal (−35.5%), strabismus (−60%), neuro-ophthalmology (−11.8%), retina (−10.6%), cataract (+16.4%), glaucoma (−37%), and miscellaneous (−45.1%). The number of people seen with viral conjunctivitis decreased by −87.1% compared to 2019. Patients with complications due to conjunctivitis also decreased: patients with pseudomembranes dropped from 16 to 4 cases and patients with corneal subepithelial infiltrates from 9 to 3 cases. Conclusions. Most diagnostic clusters showed a similar decrease. Clusters that included vision-threating conditions (retina, neuro-ophthalmology, and uveitis) remained mostly stable. During the COVID-19 lockdown, the diagnosis of adenoviral conjunctivitis decreased nearly 10 times. This fact may represent a decrease in the transmission of these infections.post-print1182 K

Impacto de la geometría del septo en el fenómeno de succión del ventrículo derecho

El impacto del fenómeno de interdependencia ventricular en la función diastólica del VD no es bien conocido. El VD es capaz de facilitar el llenado generando presión (P) negativa al inicio de la diástole pero los mecanismos implicados en este fenómeno están aún por dilucidar. Nos propusimos analizar la contribución de las fuerzas de retroceso elástico al llenado del VD y su relación con la geometría del septo

Survival analysis of time to SARS-CoV-2 PCR negativisation to optimise PCR prescription in health workers: the Henares COVID-19 healthcare workers cohort study.

Objectives Reverse transcriptase PCR (RT-PCR) is considered the gold standard in diagnosing COVID-19. Infected healthcare workers do not go back to work until RT-PCR has demonstrated that the virus is no longer present in the upper respiratory tract. The aim of this study is to determine the most efficient time to perform RT-PCR prior to healthcare workers’ reincorporation. Materials and methods This is a cohort study of healthcare workers with RT-PCR-confirmed COVID-19. Data were collected using the medical charts of healthcare workers and completed with a telephone interview. Kaplan-Meier curves were used to determine the influence of several variables on the time to RT-PCR negativisation. The impact of the variables on survival was assessed using the Breslow test. A Cox regression model was developed including the associated variables. Results 159 subjects with a positive RT-PCR out of 374 workers with suspected COVID-19 were included. The median time to negativisation was 25 days from symptom onset (IQR 20–35 days). Presence of IgG, dyspnoea, cough and throat pain were associated with significant longer time to negativisation. Cox logistic regression was used to adjust for confounding variables. Only dyspnoea and cough remained in the model as significant determinants of prolonged negativisation time. Adjusted HRs were 0.68 (0.48–096) for dyspnoea and 0.61 (0.42–0.88) for dry cough. Conclusions RT-PCR during the first 3 weeks leads to a high percentage of positive results. In the presence of respiratory symptoms, negativisation took nearly 1 week more. Those who developed antibodies needed longer time to negativisate.pre-print396 K

Assessment of diastolic chamber properties of the right ventricle by global fitting of pressure-volume data and conformational analysis of 3D + T echocardiographic sequences

Assessment of diastolic chamber properties of the right ventricle by global fitting of pressure-volume data and conformational analysis of 3D + T echocardiographic sequence

A clinical method for mapping and quantifying blood stasis in the left ventricle

In patients at risk of intraventrcular thrombosis, the benefits of chronic anticoagulation therapy need to be balanced with the pro-hemorrhagic effects of therapy. Blood stasis in the cardiac chambers is a recognized risk factor for intracardiac thrombosis and potential cardiogenic embolic events. In this work, we present a novel flow image-based method to assess the location and extent of intraventricular stasis regions inside the left ventricle (LV) by digital processing flow-velocity images obtained either by phase-contrast magnetic resonance (PCMR) or 2D color-Doppler velocimetry (echo-CDV). This approach is based on quantifying the distribution of the blood Residence Time (TR) from time-resolved blood velocity fields in the LV. We tested the new method in illustrative examples of normal hearts, patients with dilated cardiomyopathy and one patient before and after the implantation of a left ventricular assist device (LVAD). The method allowed us to assess in-vivo the location and extent of the stasis regions in the LV. Original metrics were developed to integrate flow properties into simple scalars suitable for a robust and personalized assessment of the risk of thrombosis. From a clinical perspective, this work introduces the new paradigm that quantitative flow dynamics can provide the basis to obtain subclinical markers of intraventricular thrombosis risk. The early prediction of LV blood stasis may result in decrease strokes by appropriate use of anticoagulant therapy for the purpose of primary and secondary prevention. It may also have a significant impact on LVAD device design and operation set-up

Stroma-regulated HMGA2 is an independent prognostic marker in PDAC and AAC

Background: The HMGA2 protein has experimentally been linked to EMT and cancer stemness. Recent studies imply that tumour-stroma interactions regulate these features and thereby contribute to tumour aggressiveness. Methods: We analysed 253 cases of pancreatic ductal adenocarcinoma (PDAC) and 155 cases of ampullary adenocarcinoma (AAC) for HMGA2 expression by IHC. The data were correlated with stroma abundance and supplemented by experimental studies. Results: HMGA2 acts as an independent prognostic marker associated with a significantly shorter overall survival in both tumour types. Overall, HMGA2-positivity was more frequent in patients with PDAC than with AAC. The HMGA2 status in tumour cells significantly correlated with the abundance of PDGFRβ-defined stroma cells. In vivo co-injection of Panc-1 cancer cells with pancreatic stellate cells increased tumour growth in a manner associated with increased HMGA2 expression. Furthermore, in vitro treatment of Panc-1 with conditioned media from PDGF-BB-activated stellate cells increased their ability to form tumour spheroids. Conclusions: This study identifies HMGA2 expression in tumour cells as an independent prognostic marker in PDAC and AAC. Correlative data analysis gives novel tissue-based evidence for a heterotypic cross-talk with stroma cells as a possible mechanism for HMGA2 induction, which is further supported by experimental models

Clonal chromosomal mosaicism and loss of chromosome Y in elderly men increase vulnerability for SARS-CoV-2

The pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2, COVID-19) had an estimated overall case fatality ratio of 1.38% (pre-vaccination), being 53% higher in males and increasing exponentially with age. Among 9578 individuals diagnosed with COVID-19 in the SCOURGE study, we found 133 cases (1.42%) with detectable clonal mosaicism for chromosome alterations (mCA) and 226 males (5.08%) with acquired loss of chromosome Y (LOY). Individuals with clonal mosaic events (mCA and/or LOY) showed a 54% increase in the risk of COVID-19 lethality. LOY is associated with transcriptomic biomarkers of immune dysfunction, pro-coagulation activity and cardiovascular risk. Interferon-induced genes involved in the initial immune response to SARS-CoV-2 are also down-regulated in LOY. Thus, mCA and LOY underlie at least part of the sex-biased severity and mortality of COVID-19 in aging patients. Given its potential therapeutic and prognostic relevance, evaluation of clonal mosaicism should be implemented as biomarker of COVID-19 severity in elderly people. Among 9578 individuals diagnosed with COVID-19 in the SCOURGE study, individuals with clonal mosaic events (clonal mosaicism for chromosome alterations and/or loss of chromosome Y) showed an increased risk of COVID-19 lethality