Medical Devices and Cybersecurity

I begin by looking at the role of cybersecurity in the medical world. The healthcare industry adopted information technology quite quickly. While the advancement was obviously beneficial and necessary to keep up with an ever-growing demand, the healthcare industry did not place any kind of pointed focus on the security of their IT department, or the sensitive information housed therein. When rapid advancements of technology outpaced the gradual advancement of hospital cybersecurity, security concerns became a difficult issue to control. There is a serious need for more advancements in hospital security. Each interconnected medical device has its own unique security risks; there is not a one size fits all approach to medical device cybersecurity. Each device presents its own risk in its own form of disruption: hacking, malware infection, and vulnerabilities by way of unauthorized access. The interconnectivity of medical devices becomes increasingly problematic with the scope of attacks on the public health sector. Confidential data is worth a lot of money and due to outdated technology, budget limitations, and resistance to change all contribute to the target on healthcare networks. Medical professionals are not trained to deal with networking and online threats. Manufacturers should be providing some sort of security on their devices, releasing patches, and ensuring secure products. While medical staff have little to do with the security of their devices, the owner of the healthcare facility can maintain (buy) strong device security and hiring capable cybersecurity team.https://digitalcommons.odu.edu/gradposters2022_cybersecurity/1000/thumbnail.jp

IoT Health Devices: Exploring Security Risks in the Connected Landscape

The concept of the Internet of Things (IoT) spans decades, and the same can be said for its inclusion in healthcare. The IoT is an attractive target in medicine; it offers considerable potential in expanding care. However, the application of the IoT in healthcare is fraught with an array of challenges, and also, through it, numerous vulnerabilities that translate to wider attack surfaces and deeper degrees of damage possible to both consumers and their confidence within health systems, as a result of patient-specific data being available to access. Further, when IoT health devices (IoTHDs) are developed, a diverse range of attacks are possible. To understand the risks in this new landscape, it is important to understand the architecture of IoTHDs, operations, and the social dynamics that may govern their interactions. This paper aims to document and create a map regarding IoTHDs, lay the groundwork for better understanding security risks in emerging IoTHD modalities through a multi-layer approach, and suggest means for improved governance and interaction. We also discuss technological innovations expected to set the stage for novel exploits leading into the middle and latter parts of the 21st century

Allele-Specific HLA Loss and Immune Escape in Lung Cancer Evolution

Immune evasion is a hallmark of cancer. Losing the ability to present neoantigens through human leukocyte antigen (HLA) loss may facilitate immune evasion. However, the polymorphic nature of the locus has precluded accurate HLA copy-number analysis. Here, we present loss of heterozygosity in human leukocyte antigen (LOHHLA), a computational tool to determine HLA allele-specific copy number from sequencing data. Using LOHHLA, we find that HLA LOH occurs in 40% of non-small-cell lung cancers (NSCLCs) and is associated with a high subclonal neoantigen burden, APOBEC-mediated mutagenesis, upregulation of cytolytic activity, and PD-L1 positivity. The focal nature of HLA LOH alterations, their subclonal frequencies, enrichment in metastatic sites, and occurrence as parallel events suggests that HLA LOH is an immune escape mechanism that is subject to strong microenvironmental selection pressures later in tumor evolution. Characterizing HLA LOH with LOHHLA refines neoantigen prediction and may have implications for our understanding of resistance mechanisms and immunotherapeutic approaches targeting neoantigens. Video Abstract [Figure presented] Development of the bioinformatics tool LOHHLA allows precise measurement of allele-specific HLA copy number, improves the accuracy in neoantigen prediction, and uncovers insights into how immune escape contributes to tumor evolution in non-small-cell lung cancer

Fc-Optimized Anti-CD25 Depletes Tumor-Infiltrating Regulatory T Cells and Synergizes with PD-1 Blockade to Eradicate Established Tumors

CD25 is expressed at high levels on regulatory T (Treg) cells and was initially proposed as a target for cancer immunotherapy. However, anti-CD25 antibodies have displayed limited activity against established tumors. We demonstrated that CD25 expression is largely restricted to tumor-infiltrating Treg cells in mice and humans. While existing anti-CD25 antibodies were observed to deplete Treg cells in the periphery, upregulation of the inhibitory Fc gamma receptor (FcγR) IIb at the tumor site prevented intra-tumoral Treg cell depletion, which may underlie the lack of anti-tumor activity previously observed in pre-clinical models. Use of an anti-CD25 antibody with enhanced binding to activating FcγRs led to effective depletion of tumor-infiltrating Treg cells, increased effector to Treg cell ratios, and improved control of established tumors. Combination with anti-programmed cell death protein-1 antibodies promoted complete tumor rejection, demonstrating the relevance of CD25 as a therapeutic target and promising substrate for future combination approaches in immune-oncology

Fc Effector Function Contributes to the Activity of Human Anti-CTLA-4 Antibodies.

With the use of a mouse model expressing human Fc-gamma receptors (FcγRs), we demonstrated that antibodies with isotypes equivalent to ipilimumab and tremelimumab mediate intra-tumoral regulatory T (Treg) cell depletion in vivo, increasing the CD8+ to Treg cell ratio and promoting tumor rejection. Antibodies with improved FcγR binding profiles drove superior anti-tumor responses and survival. In patients with advanced melanoma, response to ipilimumab was associated with the CD16a-V158F high affinity polymorphism. Such activity only appeared relevant in the context of inflamed tumors, explaining the modest response rates observed in the clinical setting. Our data suggest that the activity of anti-CTLA-4 in inflamed tumors may be improved through enhancement of FcγR binding, whereas poorly infiltrated tumors will likely require combination approaches

Phylogenetic ctDNA analysis depicts early-stage lung cancer evolution.

The early detection of relapse following primary surgery for non-small-cell lung cancer and the characterization of emerging subclones, which seed metastatic sites, might offer new therapeutic approaches for limiting tumour recurrence. The ability to track the evolutionary dynamics of early-stage lung cancer non-invasively in circulating tumour DNA (ctDNA) has not yet been demonstrated. Here we use a tumour-specific phylogenetic approach to profile the ctDNA of the first 100 TRACERx (Tracking Non-Small-Cell Lung Cancer Evolution Through Therapy (Rx)) study participants, including one patient who was also recruited to the PEACE (Posthumous Evaluation of Advanced Cancer Environment) post-mortem study. We identify independent predictors of ctDNA release and analyse the tumour-volume detection limit. Through blinded profiling of postoperative plasma, we observe evidence of adjuvant chemotherapy resistance and identify patients who are very likely to experience recurrence of their lung cancer. Finally, we show that phylogenetic ctDNA profiling tracks the subclonal nature of lung cancer relapse and metastasis, providing a new approach for ctDNA-driven therapeutic studies

On the relational dynamics of caring: a psychotherapeutic approach to emotional and power dimensions of women’s care work

Care is double-edged and paradoxical, inspiring a vast range of strong feelings in both care-givers and care-recipients. This paper draws on ideas about psychotherapeutic relationships to offer a theorisation of the complex emotional and power dynamics and imaginative geographies of care. Examining the humanistic approach developed by Carl Rogers as well as the psychoanalytic tradition, I advance an interpretation of psychotherapeutic practices that foregrounds the fundamental importance of the emotional and power-inflected relationship between practitioners and those with whom they work. I show how different traditions offer conceptualisations of the shape of therapeutic relationships that are highly relevant to consideration of the emotional and power dynamics of giving and receiving care. Against this background I discuss current debates about care, emotions and power, drawing especially on feminist and disability perspectives and arguing that psychotherapeutic approaches offer a powerful lens through which to understand the emotional and power dynamics of caring relationships. I conclude by emphasising how this theorisation helps to illuminate ubiquitous features of women’s care work

Effect of angiotensin-converting enzyme inhibitor and angiotensin receptor blocker initiation on organ support-free days in patients hospitalized with COVID-19

IMPORTANCE Overactivation of the renin-angiotensin system (RAS) may contribute to poor clinical outcomes in patients with COVID-19. Objective To determine whether angiotensin-converting enzyme (ACE) inhibitor or angiotensin receptor blocker (ARB) initiation improves outcomes in patients hospitalized for COVID-19. DESIGN, SETTING, AND PARTICIPANTS In an ongoing, adaptive platform randomized clinical trial, 721 critically ill and 58 non–critically ill hospitalized adults were randomized to receive an RAS inhibitor or control between March 16, 2021, and February 25, 2022, at 69 sites in 7 countries (final follow-up on June 1, 2022). INTERVENTIONS Patients were randomized to receive open-label initiation of an ACE inhibitor (n = 257), ARB (n = 248), ARB in combination with DMX-200 (a chemokine receptor-2 inhibitor; n = 10), or no RAS inhibitor (control; n = 264) for up to 10 days. MAIN OUTCOMES AND MEASURES The primary outcome was organ support–free days, a composite of hospital survival and days alive without cardiovascular or respiratory organ support through 21 days. The primary analysis was a bayesian cumulative logistic model. Odds ratios (ORs) greater than 1 represent improved outcomes. RESULTS On February 25, 2022, enrollment was discontinued due to safety concerns. Among 679 critically ill patients with available primary outcome data, the median age was 56 years and 239 participants (35.2%) were women. Median (IQR) organ support–free days among critically ill patients was 10 (–1 to 16) in the ACE inhibitor group (n = 231), 8 (–1 to 17) in the ARB group (n = 217), and 12 (0 to 17) in the control group (n = 231) (median adjusted odds ratios of 0.77 [95% bayesian credible interval, 0.58-1.06] for improvement for ACE inhibitor and 0.76 [95% credible interval, 0.56-1.05] for ARB compared with control). The posterior probabilities that ACE inhibitors and ARBs worsened organ support–free days compared with control were 94.9% and 95.4%, respectively. Hospital survival occurred in 166 of 231 critically ill participants (71.9%) in the ACE inhibitor group, 152 of 217 (70.0%) in the ARB group, and 182 of 231 (78.8%) in the control group (posterior probabilities that ACE inhibitor and ARB worsened hospital survival compared with control were 95.3% and 98.1%, respectively). CONCLUSIONS AND RELEVANCE In this trial, among critically ill adults with COVID-19, initiation of an ACE inhibitor or ARB did not improve, and likely worsened, clinical outcomes. TRIAL REGISTRATION ClinicalTrials.gov Identifier: NCT0273570