Balancing Privacy and Progress in Artificial Intelligence: Anonymization in Histopathology for Biomedical Research and Education

The advancement of biomedical research heavily relies on access to large amounts of medical data. In the case of histopathology, Whole Slide Images (WSI) and clinicopathological information are valuable for developing Artificial Intelligence (AI) algorithms for Digital Pathology (DP). Transferring medical data "as open as possible" enhances the usability of the data for secondary purposes but poses a risk to patient privacy. At the same time, existing regulations push towards keeping medical data "as closed as necessary" to avoid re-identification risks. Generally, these legal regulations require the removal of sensitive data but do not consider the possibility of data linkage attacks due to modern image-matching algorithms. In addition, the lack of standardization in DP makes it harder to establish a single solution for all formats of WSIs. These challenges raise problems for bio-informatics researchers in balancing privacy and progress while developing AI algorithms. This paper explores the legal regulations and terminologies for medical data-sharing. We review existing approaches and highlight challenges from the histopathological perspective. We also present a data-sharing guideline for histological data to foster multidisciplinary research and education.Comment: Accepted to FAIEMA 202

Deep Learning for Predicting Metastasis on Melanoma WSIs

Northern Europe has the second highest mortality rate of melanoma globally. In 2020, the mortality rate of melanoma rose to 1.9 per 100 000 habitants. Melanoma prognosis is based on a pathologist's subjective visual analysis of the patient's tumor. This methodology is heavily time-consuming, and the prognosis variability among experts is notable, drastically jeopardizing its reproducibility. Thus, the need for faster and more reproducible methods arises. Machine learning has paved its way into digital pathology, but so far, most contributions are on localization, segmentation, and diagnostics, with little emphasis on prognostics. This paper presents a convolutional neural network (CNN) method based on VGG16 to predict melanoma prognosis as the presence of metastasis within five years. Patches are extracted from regions of interest from Whole Slide Images (WSIs) at different magnification levels used in model training and validation. Results infer that utilizing WSI patches at 20x magnification level has the best performance, with an F1 score of 0.7667 and an AUC of 0.81

End-of-life care in a COPD patient awaiting lung transplantation: a case report

COPD is nowadays the main indication for lung transplantation. In appropriately selected patients with end stage COPD, lung transplantation may improve quality of life and prognosis of survival. However, patients with end stage COPD may die while waiting for lung transplantation. Palliative care is important to address the needs of patients with end stage COPD. This case report shows that in a patient with end stage COPD listed for lung transplantation offering palliative care and curative-restorative care concurrently may be problematic. If the requirements to remain a transplantation candidate need to be met, the possibilities for palliative care may be limited. Discussing the possibilities of palliative care and the patient's treatment preferences is necessary to prevent that end-of-life care needs of COPD patients dying while listed for lung transplantation are not optimally addressed. The patient's end-of-life care preferences may ask for a clear distinction between the period in which palliative and curative-restorative care are offered concurrently and the end-of-life care period. This may be necessary to allow a patient to spend the last stage of life according to his or her wishes, even when this implicates that lung transplantation is not possible anymore and the patient will die because of end stage COPD

Combined HER3-EGFR score in triple-negative breast cancer provides prognostic and predictive significance superior to individual biomarkers

© 2020, The Author(s). Epidermal growth factor receptor (EGFR) and human epidermal growth factor receptor 3 (HER3) have been investigated as triple-negative breast cancer (TNBC) biomarkers. Reduced EGFR levels can be compensated by increases in HER3; thus, assaying EGFR and HER3 together may improve prognostic value. In a multi-institutional cohort of 510 TNBC patients, we analyzed the impact of HER3, EGFR, or combined HER3-EGFR protein expression in pre-treatment samples on breast cancer-specific and distant metastasis-free survival (BCSS and DMFS, respectively). A subset of 60 TNBC samples were RNA-sequenced using massive parallel sequencing. The combined HER3-EGFR score outperformed individual HER3 and EGFR scores, with high HER3-EGFR score independently predicting worse BCSS (Hazard Ratio [HR] = 2.30, p = 0.006) and DMFS (HR = 1.78, p = 0.041, respectively). TNBCs with high HER3-EGFR scores exhibited significantly suppressed ATM signaling and differential expression of a network predicted to be controlled by low TXN activity, resulting in activation of EGFR, PARP1, and caspases and inhibition of p53 and NFκB. Nuclear PARP1 protein levels were higher in HER3-EGFR-high TNBCs based on immunohistochemistry (p = 0.036). Assessing HER3 and EGFR protein expression in combination may identify which adjuvant chemotherapy-treated TNBC patients have a higher risk of treatment resistance and may benefit from a dual HER3-EGFR inhibitor and a PARP1 inhibitor

Clustering of 27,525,663 death records from the United States based on health conditions associated with death: an example of big health data exploration

Background: Insight into health conditions associated with death can inform healthcare policy. We aimed to cluster 27,525,663 deceased people based on the health conditions associated with death to study the associations between the health condition clusters, demographics, the recorded underlying cause and place of death. Methods: Data from all deaths in the United States registered between 2006 and 2016 from the National Vital Statistics System of the National Center for Health Statistics were analyzed. A self-organizing map (SOM) was used to create an ordered representation of the mortality data. Results: 16 clusters based on the health conditions associated with death were found showing significant differences in socio-demographics, place, and cause of death. Most people died at old age (73.1 (18.0) years) and had multiple health conditions. Chronic ischemic heart disease was the main cause of death. Most people died in the hospital or at home. Conclusions: The prevalence of multiple health conditions at death requires a shift from disease-oriented towards person-centred palliative care at the end of life, including timely advance care planning. Understanding differences in population-based patterns and clusters of end-of-life experiences is an important step toward developing a strategy for implementing population-based palliative care

Respiratory adverse effects of opioids for breathlessness: a systematic review and meta-analysis

Background: Previous studies have shown that opioids can reduce chronic breathlessness in advanced disease. However, physicians remain reluctant to prescribe opioids for these patients, commonly due to fear of respiratory adverse effects. Aim: To systematically review reported respiratory adverse effects of opioids in patients with advanced disease and chronic breathlessness. Methods: Pubmed, Embase, Cochrane central register of controlled trials, CINAHL, ClinicalTrials.gov and the reference lists of relevant systematic reviews were searched. Two independent researchers screened against predefined inclusion criteria and extracted data. Meta-analysis was conducted where possible. Results: We included 63 out of 1990 articles, describing 67 studies. Meta-analysis showed an increase in partial pressure of carbon dioxide (0.27 kPa; 95% CI 0.08 to 0.45) and no significant change in partial pressure of oxygen and oxygen saturation (both p>0.05). Non-serious respiratory depression (definition variable/not stated) was described in 4/1064 patients. One cancer patient pre-treated with morphine for pain needed temporary respiratory support following nebulized morphine for breathlessness (single case study). Conclusions: We found no evidence of significant or clinically relevant respiratory adverse effects of opioids for chronic breathlessness. Heterogeneity of design and study population, and low study quality are limitations. Larger studies designed to detect respiratory adverse effects are needed

Copper-Heparin Inhalation Therapy To Repair Emphysema:A Scientific Rationale

Current pharmacotherapy of chronic obstructive pulmonary disease (COPD) aims at reducing respiratory symptoms and exacerbation frequency. Effective therapies to reduce disease progression, however, are still lacking. Furthermore, COPD medications showed less favorable effects in emphysema than in other COPD phenotypes. Elastin fibers are reduced and disrupted, whereas collagen levels are increased in emphysematous lungs. Protease/antiprotease imbalance has historically been regarded as the sole cause of emphysema. However, it is nowadays appreciated that emphysema may also be provoked by perturbations in the sequential repair steps following elastolysis. Essentiality of fibulin-5 and lysyl oxidase-like 1 in the elastin restoration process is discussed, and it is argued that copper deficiency is a plausible reason for failing elastin repair in emphysema patients. Since copper-dependent lysyl oxidases crosslink elastin as well as collagen fibers, copper supplementation stimulates accumulation of both proteins in the extracellular matrix. Restoration of abnormal elastin fibers in emphysematous lungs is favorable, whereas stimulating pulmonary fibrosis formation by further increasing collagen concentrations and organization is detrimental. Heparin inhibits collagen crosslinking while stimulating elastin repair and might therefore be the ideal companion of copper for emphysema patients. Efficacy and safety considerations may lead to a preference of pulmonary administration of copper-heparin over systemic administration