Monitoring Modalities Research Articles

Rigorous and long-term cardiac monitoring strategy in cryptogenic stroke or TIA patients in a tertiary care centre results in a two-fold increase in AF detection

Abstract Funding Acknowledgements Type of funding sources: Public Institution(s). Main funding source(s): Special Research Fund (Bijzonder Onderzoeksfonds, BOF) Hasselt University. This study is part of Limburg Clinical Research Center, supported by the foundation Limburg Sterk Merk, province of Limburg, Flemish government, Hasselt University, Ziekenhuis Oost-Limburg and Jessa Hospital. Background Atrial fibrillation (AF) is a major cause of ischaemic stroke. Oral anticoagulation is recommended in stroke survivors with AF to prevent recurrence. Prolonged ECG monitoring using insertable cardiac monitors (ICMs) has been shown to increase the detection rate of AF compared to standard 24-hour ECG monitoring in cryptogenic stroke patients. However, prolonged ambulatory ECG monitoring is underutilized, likely contributing to an underdiagnosis of AF and missed anticoagulation treatment opportunities for secondary stroke prevention. Purpose This study aims to evaluate how our evolving cardiac monitoring strategy affected AF detection rates one year after cryptogenic ischaemic stroke or transient ischaemic attack (TIA) in a tertiary care centre. Methods We retrospectively identified all consecutive cryptogenic stroke or TIA patients admitted to our centre between 1/01/2017 – 1/01/2022. Patients with a pacemaker or implantable cardioverter-defibrillator were excluded from the analysis. Data were collected from the electronic medical record. Available cardiac monitoring modalities included 24-hour Holter monitoring, 7-day Holter monitoring, and insertable cardiac monitors (ICM). After October 2020 (i.e., period 2), the latter became part of our routine diagnostic workup for AF detection in case extended (7-day) Holter monitoring was negative. Results All 691 cryptogenic stroke or TIA patients admitted to our hospital during the inclusion period were considered. These were elderly patients (69.7 ± 13.2 years) with a CHA2DS2-VASc score of 3 [2 - 5]. Figure 1 shows evolving trends in the use of the different cardiac monitoring tools before and after October 2020. In particular, the use of 7-day Holter monitoring and long-term continuous monitoring with ICM increased after implementing our new diagnostic protocol compared to 24-hour Holter monitoring (p<.001). ICMs were inserted 95 [66 – 145] days after index stroke or TIA. The new diagnostic protocol detected more AF one year after the index stroke or TIA (3.7% vs. 10.1%, p<.001, Figure 2). In 95.6% of patients with AF detected within one year, oral anticoagulation was initiated. Future research should determine whether adopting a strategy of routine ICM following cryptogenic stroke and, thus, more appropriate anticoagulant therapy may improve clinical outcome in these patients. Conclusions The increased use of prolonged cardiac monitoring in cryptogenic stroke or TIA patients resulted in a two-fold increase in AF detection one year after stroke. Therefore, our results underscore the need to implement guideline-recommended prolonged rhythm monitoring using ICMs in addition to short-term ECG monitoring to ensure adequate secondary stroke prevention.

Giant Cell Arteritis: State of the Art in Diagnosis, Monitoring, and Treatment.

Giant cell arteritis (GCA) is the most prevalent subtype of vasculitis in adults. In recent years, there has been substantial improvement in the diagnosis and treatment of GCA, mainly attributed to the introduction of highly sensitive diagnostic tools, incorporation of modern imaging modalities for diagnosis and monitoring of large-vessel vasculitis, and introduction of highly effective novel biological therapies that have revolutionized the field of GCA. This article reviews state-of-the-art approaches for the diagnosis, monitoring, and treatment options of GCA.

Integrated circulating tumour DNA and cytokine analysis for therapy monitoring of ALK-rearranged lung adenocarcinoma

BackgroundDetection of circulating tumour DNA (ctDNA) in biological fluids is a minimally invasive alternative to tissue biopsy for therapy monitoring. Cytokines are released in the tumour microenvironment to influence inflammation and tumorigenic mechanisms. Here, we investigated the potential biomarker utility of circulating cytokines vis-à-vis ctDNA in ALK-rearranged+ lung adenocarcinoma (ALK + NSCLC) and explored the optimal combination of molecular parameters that could indicate disease progression.MethodsLongitudinal serum samples (n = 296) were collected from ALK + NSCLC patients (n = 38) under tyrosine kinase inhibitor (TKI) therapy and assayed to quantify eight cytokines: IFN-γ, IL-1β, IL-6, IL-8, IL-10, IL-12p70, MCP1 and TNF-α. Generalised linear mixed-effect modelling was performed to test the performance of different combinations of cytokines and previously determined ctDNA parameters in identifying progressive disease.ResultsSerum IL-6, IL-8 and IL-10 were elevated at progressive disease, with IL-8 having the most significant impact as a biomarker. Integrating changes in IL-8 with ctDNA parameters maximised the performance of the classifiers in identifying disease progression, but this did not significantly outperform the model based on ctDNA alone.ConclusionsSerum cytokine levels are potential disease progression markers in ALK + NSCLC. Further validation in a larger and prospective cohort is necessary to determine whether the addition of cytokine evaluation could improve current tumour monitoring modalities in the clinical setting.

Glycemic Control by Treatment Modalities: National Registry-Based Population Data in Children and Adolescents with Type 1 Diabetes

Introduction: The aim of the study was to assess the differences in key parameters of type 1 diabetes (T1D) control associated with treatment and monitoring modalities including newly introduced hybrid closed-loop (HCL) algorithm in children and adolescents with T1D (CwD) using the data from the population-wide pediatric diabetes registry ČENDA. Methods: CwD younger than 19 years with T1D duration >1 year were included and divided according to the treatment modality and type of CGM used: multiple daily injection (MDI), insulin pump without (CSII) and with HCL function, intermittently scanned continuous glucose monitoring (isCGM), real-time CGM (rtCGM), and intermittent or no CGM (noCGM). HbA1c, times in glycemic ranges, and glucose risk index (GRI) were compared between the groups. Results: Data of a total of 3,251 children (mean age 13.4 ± 3.8 years) were analyzed. 2,187 (67.3%) were treated with MDI, 1,064 (32.7%) with insulin pump, 585/1,064 (55%) with HCL. The HCL users achieved the highest median TIR 75.4% (IQR 6.3) and lowest GRI 29.1 (7.8), both p < 0.001 compared to other groups, followed by MDI rtCGM and CSII groups with TIR 68.8% (IQR 9.0) and 69.0% (7.5), GRI 38.8 (12.5) and 40.1 (8.5), respectively (nonsignificant to each other). These three groups did not significantly differ in their HbA1c medians (51.8 [IQR 4.5], 50.7 [4.5], and 52.7 [5.7] mmol/mol, respectively). NoCGM groups had the highest HbA1c and GRI and lowest TIR regardless of the treatment modality. Conclusion: This population-based study shows that the HCL technology is superior to other treatment modalities in CGM-derived parameters and should be considered as a treatment of choice in all CwD fulfilling the indication criteria.

The elephant in the room: cybersecurity in healthcare.

Cybersecurity has seen an increasing frequency and impact of cyberattacks and exposure of Protected Health Information (PHI). The uptake of an Electronic Medical Record (EMR), the exponential adoption of Internet of Things (IoT) devices, and the impact of the COVID-19 pandemic has increased the threat surface presented for cyberattack by the healthcare sector.Within healthcare generally and, more specifically, within anaesthesia and Intensive Care, there has been an explosion in wired and wireless devices used daily in the care of almost every patient-the Internet of Medical Things (IoMT); ventilators, anaesthetic machines, infusion pumps, pacing devices, organ support and a plethora of monitoring modalities. All of these devices, once connected to a hospital network, present another opportunity for a malevolent party to access the hospital systems, either to gain PHI for financial, political or other gain or to attack the systems directly to cause erroneous monitoring, altered settings of any device and even to access the EMR via this IoMT window.This exponential increase in the IoMT and the increasing wireless connectivity of anaesthesia and ICU devices as well as implantable devices presents a real and present danger to patient safety. There has, at the same time, been a chronic underfunding of cybersecurity in healthcare.This lack of cybersecurity investment has left the sectorexposed, and with the monetisation of PHI, the introduction of technically unsecure IoT devices for monitoring and direct patient care, the healthcare sector is presenting itself for further devastating cyberattacks or breaches of PHI. Coupled with the immense strain that the COVID-19 pandemic has placed on healthcare and the changes in working patterns of many caregivers, this has further amplified the exposure of the sector to cyberattacks.

Non‐Invasive Touch‐Based Lithium Monitoring Using an Organohydrogel‐Based Sensing Interface

AbstractLithium is a drug widely employed for the treatment of bipolar disorder owing to its high efficacy in mood management and suicide prevention. However, this efficacy is often undermined by misdosing and nonadherence, and diligent drug monitoring is required during treatment. Standard lithium monitoring involves invasive blood collections and laboratory analysis with low time granularity. Recent advances in sensor technology have enabled the development of personalized drug‐monitoring devices that analyze biomarker information noninvasively. Herein, based on the fact that the analyte partition onto the fingertip with a high flux, a touch‐based noninvasive monitoring modality for managing lithium pharmacotherapy is devised. The system is built based on a thin organohydrogel‐mounted lithium ion‐selective electrode (TOH‐ISE). The TOH coating provides a stable environment for sensing. Through the utilization of a water/glycerol bi‐solvent matrix, the gel exhibits dehydration‐resist properties, rendering a controlled micro‐environment for ISE conditioning, and subsequently minimizing signal drift. To illustrate the clinical application of the solution, the system is tested on a subject prescribed lithium. The system successfully detected the increase in circulating drug levels following medication intake. Collectively, the results indicate the devised solution is capable to facilitate lithium adherence monitoring and has broader potential for optimizing lithium pharmacotherapy.

Intestinal ultrasound as a non-invasive tool to monitor inflammatory bowel disease activity and guide clinical decision making

Intestinal ultrasound (IUS) is a non-invasive, real-time, cross-sectional imaging tool that can be used at the point-of-care to assess disease activity in patients with Crohn's disease or ulcerative colitis. IUS promotes quick and impactful treatment decisions that can modify disease progression and enhance patient compliance. This review will summarize the technical aspects of IUS, the evidence to support the use of IUS in disease activity monitoring, the comparison of IUS to current standard of care monitoring modalities such as colonoscopy and calprotectin, and the optimal positioning of IUS in a tight-control monitoring strategy.

A Low-Frequency Portable Continuous Wave Radar System for Vital Signs Monitoring

Modalities for continuous real-time heart rate and respiration rate monitoring is a crucial diagnostic tool, specifically in the early detection of potential health risks and timely intervention to reduce fatality. A low-frequency chest-wearable continuous wave radar device ( <italic xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">RDR–SENSE</i> ) has been designed and developed for continuous monitoring of heart rate and respiration rate. The developed RDR–SENSE device detects the periodic movements in the human thoracic region associated with cardio-pulmonary activities. The chest-wearable low-power RDR–SENSE device has been designed and manufactured in small size (5cm x 5cm). Five volunteers’ cardio-pulmonary activities were collected using the device in five different respiratory scenarios, and a precise signal processing algorithm was applied to derive their heart rate and respiration rate data. The measured data were compared with reference signals to evaluate the RDR–SENSE’s performance. The measured heart and respiration rates were highly promising in terms of accuracy. The mean absolute error was one beat per minute for the heart rate and 0.75 respiration per minute for the respiration rate. The root mean square error was 1.55 BPM for the heart rate and 1.25 RPM for the respiration rate. The developed RDR–SENSE explores the prospects of a chest-wearable, compact, low-frequency radar device for accurate continuous heart rate and respiration rate measurements during seated activities that resemble daily-life study or work.

The Influence of Extracerebral Tissue on Continuous Wave Near-Infrared Spectroscopy in Adults: A Systematic Review of In Vivo Studies.

Near-infrared spectroscopy (NIRS) is a non-invasive technique for measuring regional tissue haemoglobin (Hb) concentrations and oxygen saturation (rSO2). It may be used to monitor cerebral perfusion and oxygenation in patients at risk of cerebral ischemia or hypoxia, for example, during cardiothoracic or carotid surgery. However, extracerebral tissue (mainly scalp and skull tissue) influences NIRS measurements, and the extent of this influence is not clear. Thus, before more widespread use of NIRS as an intraoperative monitoring modality is warranted, this issue needs to be better understood. We therefore conducted a systematic review of published in vivo studies of the influence of extracerebral tissue on NIRS measurements in the adult population. Studies that used reference techniques for the perfusion of the intra- and extracerebral tissues or that selectively altered the intra- or extracerebral perfusion were included. Thirty-four articles met the inclusion criteria and were of sufficient quality. In 14 articles, Hb concentrations were compared directly with measurements from reference techniques, using correlation coefficients. When the intracerebral perfusion was altered, the correlations between Hb concentrations and intracerebral reference technique measurements ranged between |r| = 0.45-0.88. When the extracerebral perfusion was altered, correlations between Hb concentrations and extracerebral reference technique measurements ranged between |r| = 0.22-0.93. In studies without selective perfusion modification, correlations of Hb with intra- and extracerebral reference technique measurements were generally lower (|r| < 0.52). Five articles studied rSO2. There were varying correlations of rSO2 with both intra- and extracerebral reference technique measurements (intracerebral: |r| = 0.18-0.77, extracerebral: |r| = 0.13-0.81). Regarding study quality, details on the domains, participant selection and flow and timing were often unclear. We conclude that extracerebral tissue indeed influences NIRS measurements, although the evidence (i.e., correlation) for this influence varies considerably across the assessed studies. These results are strongly affected by the study protocols and analysis techniques used. Studies employing multiple protocols and reference techniques for both intra- and extracerebral tissues are therefore needed. To quantitatively compare NIRS with intra- and extracerebral reference techniques, we recommend applying a complete regression analysis. The current uncertainty regarding the influence of extracerebral tissue remains a hurdle in the clinical implementation of NIRS for intraoperative monitoring. The protocol was pre-registered in PROSPERO (CRD42020199053).

Abstract 3301: Ultrasensitive compartment-free digital phenotyping of circulating extracellular vesicles for diagnosis of Ewing sarcoma

Abstract Ewing sarcoma (EWS) is the second most common pediatric osseous malignancy in the US. Vague symptoms and high prevalence of metastasis and recurrence present serious obstacles to its clinical management. Current diagnostic and monitoring modalities for EWS, including tissue biopsy, imaging, and cytogenetics have limitations in the early diagnosis and disease monitoring. Thus, EWS patients, as do other solid pediatric cancers, face unique challenges in the lack of non-invasive tests to aid with patient management. Extracellular vesicles (EVs), including exosomes, are emerging as a new paradigm of liquid biopsy for non-invasive cancer diagnosis and monitoring owing to their informative cargoes and imperative biological functions. However, limited progresses have been reported in the field of EWS-related EV diagnostics. To address this gap, we developed a new microfluidics-based digital immunoassay platform, termed μTUNER (microfluidic Topographic modUlation and iNtensification of Enzymatic Reaction), for ultrasensitive single-molecular analysis of EV protein biomarkers and liquid biopsy-based diagnosis of EWS. Through constructing nanoconfinements with tunable sizes, this technology affords programmable patterning and modulation of surface enzymatic reactions in a non-contact manner. Such unique capacity enables us to develop a compartment-free digital immunoassay platform which is conceptually distinct from the existing digital assays. As a proof-of-concept for clinical applications, we adapted the μTUNER digital immunoassay platform to quantitatively evaluate four exo-protein biomarkers (CD99, ENO-2, NGFR, and Ezrin) that we identified by extensive proteomics analysis of EWS cell line-derived EVs (PMID: 32821345). Using protein standards and EWS cell line-derived EVs, we demonstrated that our technology affords sensitive and quantitative detection of exo-protein biomarkers with LODs at the fg/mL level, which warrants subsequent assessment of its adaptability to clinical EWS diagnosis. EV profiling of plasma samples from adult and pediatric EWS patients (n = 16) and matched healthy controls (n = 17) reveals unique expression patterns of the four markers. These exo-protein biomarkers individually afforded excellent diagnostic performance (AUC, CD99: 0.992; ENO-2: 0.985; NGFR: 0.996; Ezrin: 0.978) to differentiate the EWS and control groups. The unweighted SUM signature of the four proteins further improves the diagnostic power to yield an AUC of 1.00. Meanwhile, the distinctive EV signature obtained from the machine learning-based analysis permits further classification of control, adult, and pediatric patients with an overall accuracy of 97%. Based on these results, we envision that our technology combined with the novel exo-protein biomarker signature can be useful clinically to improve the diagnosis of patients with Ewing sarcoma. Citation Format: Yunjie Wen, Vikalp Vishwakarma, Andrew K. Godwin, Yong Zeng. Ultrasensitive compartment-free digital phenotyping of circulating extracellular vesicles for diagnosis of Ewing sarcoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 3301.

393 Sonolucent Cranioplasty for Real-Time Ultrasound Monitoring of Extra-to-Intracranial Bypass: Early Multicenter Experience of 44 Cases

INTRODUCTION: The new sonolucent cranioplasty implant (clear polymethyl methacrylate, PMMA) adds functionality besides reconstruction during and after surgery. One possible application uses transcranioplasty ultrasound (TCUS) technique after PMMA cranioplasty to assess graft patency of extracranial-intracranial (EC-IC) bypass procedures. METHODS: Multicenter analysis of consecutive EC-IC bypass patients from 5 US centers between 2019-2022 with closure post bypass using the translucent PMMA cranioplasty implant. RESULTS: Forty-four patients (median-age 53, 68.2% females) were included. The most common indication for bypass was Moyamoya disease/syndrome (77.3%) and superficial temporal artery to middle cerebral artery (STA-MCA) bypass was the most common procedure (79.5%). Pre-treatment modified Rankin Scale of 0 and 1-2 was noted in 11.4% and 59.1% of the patients, respectively, with hypertension being the most common comorbidity (72.7%). Intraoperative imaging for bypass patency involved utilizing combination of modalities in all patients, with intraoperative doppler being the most commonly utilized monitoring modality (90.9%) followed by indocyanine green (ICG) and catheter angiography (86.4% and 61.4%, respectively). Qualitative TCUS assessment of the graft patency was feasible in all cases without technical difficulties. Post-operative inpatient TCUS confirmation of the bypass patency was recorded in 56.8% of the cases, and outpatient TCUS surveillance for monitoring bypass patency through the implant was recorded in 22.7% of the patients. There were no cases of bypass failure noted in this cohort necessitating retreatment. Similarly, no implant-related complications were encountered in the cohort. Major complications requiring additional surgery occurred in 2 patients (4.6%) including epidural hematoma requiring surgical evacuation (2.3%) and post-operative surgical site infection (2.3%) that was unrelated to the implant. CONCLUSIONS: This multicenter study supports the safety and feasibility of using the sonolucent PMMA implant in the setting of EC-IC bypass surgery with the goal to monitor bypass patency using TCUS.

Detection of Atrial Fibrillation in Patients Admitted with Ischaemic Stroke: A Non-systematic Review of the Asian Population

Stroke with AF is often associated with high recurrence rates. However, many patients with ischaemic stroke do not have a history of AF and show sinus rhythm and the absence of AF on their admission ECG. The detection of AF remains challenging due to its intermittent nature. Therefore, the ultimate goal of cardiac monitoring after cerebral ischaemic events is to detect AF so that oral anticoagulants can be prescribed to prevent the recurrence of a second, more debilitating or fatal stroke. In this article, AF detection in hospitalised patients with ischaemic stroke is discussed, with a focus on the Asian population. The AF detection rates in Asian cohorts are compared with those of major studies in the Western population; the utility and limitations of various cardiac monitoring modalities in Asian populations and healthcare systems and emerging technologies that could potentially detect AF in the stroke population are summarised and clinical practice and evidence gaps in detecting AF to prevent stroke recurrence are discussed.

Nanotheranostics: application of nanosensors in diabetes management.

The objective of the present study is to discuss the use of nanomaterials like nanosensors for diagnosing Diabetes and highlight their applications in the treatment of Diabetes. Diabetes mellitus (D.M.) is a group of metabolic diseases characterized by hyperglycemia. Orally administered antidiabetic drugs like glibenclamide, glipalamide, and metformin can partially lower blood sugar levels, but long-term use causes kidney and liver damage. Recent breakthroughs in nanotheranostics have emerged as a powerful tool for diabetes treatment and diagnosis. Nanotheranostics is a rapidly developing area that can revolutionize diabetes diagnosis and treatment by combining therapy and imaging in a single probe, allowing for pancreas-specific drug and insulin delivery. Nanotheranostic in Diabetes research has facilitated the development of improved glucose monitoring and insulin administration modalities, which promise to improve the quality of life for people with Diabetes drastically. Further, nanomaterials like nanocarriers and unique functional nanomaterials used as nano theranostics tools for treating Diabetes will also be highlighted. The nanosensors discussed in this review article will encourage researchers to develop innovative nanomaterials with novel functionalities and properties for diabetes detection and treatment.

Objective Prediction of Next-Day's Affect Using Multimodal Physiological and Behavioral Data: Algorithm Development and Validation Study.

Affective states are important aspects of healthy functioning; as such, monitoring and understanding affect is necessary for the assessment and treatment of mood-based disorders. Recent advancements in wearable technologies have increased the use of such tools in detecting and accurately estimating mental states (eg, affect, mood, and stress), offering comprehensive and continuous monitoring of individuals over time. Previous attempts to model an individual's mental state relied on subjective measurements or the inclusion of only a few objective monitoring modalities (eg, smartphones). This study aims to investigate the capacity of monitoring affect using fully objective measurements. We conducted a comparatively long-term (12-month) study with a holistic sampling of participants' moods, including 20 affective states. Longitudinal physiological data (eg, sleep and heart rate), as well as daily assessments of affect, were collected using 3 modalities (ie, smartphone, watch, and ring) from 20 college students over a year. We examined the difference between the distributions of data collected from each modality along with the differences between their rates of missingness. Out of the 20 participants, 7 provided us with 200 or more days' worth of data, and we used this for our predictive modeling setup. Distributions of positive affect (PA) and negative affect (NA) among the 7 selected participants were observed. For predictive modeling, we assessed the performance of different machine learning models, including random forests (RFs), support vector machines (SVMs), multilayer perceptron (MLP), and K-nearest neighbor (KNN). We also investigated the capability of each modality in predicting mood and the most important features of PA and NA RF models. RF was the best-performing model in our analysis and performed mood and stress (nervousness) prediction with ~81% and ~72% accuracy, respectively. PA models resulted in better performance compared to NA. The order of the most important modalities in predicting PA and NA was the smart ring, phone, and watch, respectively. SHAP (Shapley Additive Explanations) analysis showed that sleep and activity-related features were the most impactful in predicting PA and NA. Generic machine learning-based affect prediction models, trained with population data, outperform existing methods, which use the individual's historical information. Our findings indicated that our mood prediction method outperformed the existing methods. Additionally, we found that sleep and activity level were the most important features for predicting next-day PA and NA, respectively.

Thoracic Ultrasound in Lung Transplantation—Insights in the Field

The use of thoracic ultrasound (TUS) is a novel and dynamic diagnostic and monitoring modality that has shown remarkable advances within the last decade, with several published papers investigating its role within the field of lung transplantation. The aim of this current opinion review is to review the existing literature on the role of TUS in all stages of LTx, from in-donor lung evaluation to graft assessment on ex vivo lung perfusion and in the short- and long-term follow-up after LTx.

Abstract P6-05-50: Lobular Breast Cancer Alliance Inc. Survey of Individuals with Metastatic Invasive Lobular Carcinoma

Abstract Background: The Lobular Breast Cancer Alliance Inc. (LBCA) is committed to raising awareness of the distinctive characteristics of invasive lobular carcinoma (ILC) and promoting and funding ILC research. Comprising 15% of all breast cancers, ILC tumors often form in a linear, sometimes diffuse fashion both within the breast and in metastatic sites, making them difficult to diagnose, monitor, and treat. LBCA surveyed individuals living with metastatic ILC (mILC) about their experiences with detection and monitoring of mILC. Methods: LBCA conducted an anonymous, online survey of persons living with mILC using SurveyMonkey. The survey was shared with LBCA newsletter subscribers, sister organizations, and via social media. Survey questions asked about metastatic site locations, imaging and monitoring modalities, and patient experience with disease progression and clinician discussions about mILC. An independent IRB review determined the study was exempt from full IRB review. Results: 241 people living with mILC completed the survey. 77% were from the US and Canada. 71% were between 35-64 years of age. 41% had been diagnosed with de novo metastatic ILC. Bone was the most common site of initial metastasis with 75% diagnosed de novo (DN) and 59% diagnosed with a distant recurrence (DR). GI metastases (including metastases to stomach, colon, bowel, peritoneum, or rectum) were reported by 11% of the DN and 14% of the DR groups, respectively. Unusual sites for breast cancer metastasis (to genitourinary organs, eye, or skin) were reported by 11% of the DN and 16% of the DR groups. Metastatic progression was reported by 47% of respondents including to bone (42%), to the liver (22%), and 40% reported progression within the initial metastatic site. 36% of individuals with DN mILC reported progression as compared to 54% among those with a DR. Both groups reported living with mILC for similar durations (on average 3.9 years for DN; 3.3 for DR). 36% of respondents reported that at least one imaging modality failed to visualize one or more of their metastatic sites at initial diagnosis of mILC. 54% of respondents with bone metastases and 19% of those with GI metastases indicated their metastases had not been visualized by standard imaging modalities. 48% of all surveyed stated their mILC was an unexpected or an incidental finding made during another medical procedure, of those, 64% were bone metastases. 25% of respondents whose metastases progressed indicated imaging failed to detect one or more of their sites of progression. In both the DN and DR groups, the most frequently utilized tests and/or procedures used to monitor for progression or changes in metastases were routine blood and tumor marker tests. Respondents with DN mILC reported an average 12 months between first report of symptoms and mILC diagnosis. Those with DR reported an average 8 months between symptom reporting and diagnosis. 42% of all respondents reported that a doctor had told them what symptoms to report at any time. 58% of respondents reported feeling that non-oncologists caring for them (primarily PCPs, radiologists, and gastroenterologists) needed to be better informed about ILC. Conclusion: Surveyed individuals confirmed the perception that mILC can occur in unique locations and be difficult to diagnose and that mILC may be challenging to monitor, and standard surveillance methods may fail to visualize mILC. While a large percent of respondents reported that their mILC diagnoses were unexpected or incidental findings during another medical procedure, this may be due to different understandings of “incidental.” This and the fact that more respondents with DR mILC reported progression than those with DN mILC warrant further study. Citation Format: Laurie B. Hutcheson, Janice Axelrod, Ann Camden, Donna J. Charlevoix, Tracy A. Cushing, Maxine S. Jochelson, Megan L. Kruse, Theresa Langdon, Julia K. Levine, Christine McKay, Otto Metzger, Mason Mitchell-Daniels, Jason Mouabbi, Barbara F. Neilsen. Lobular Breast Cancer Alliance Inc. Survey of Individuals with Metastatic Invasive Lobular Carcinoma [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr P6-05-50.

Abstract OT3-11-01: TK IMPACT: Treatment Monitoring of Hormone Receptor Positive (HR+), HER2 Negative (HER2-) Metastatic Breast Cancer (MBC) Patients Receiving CDK 4/6 Inhibitors (CDK4/6i) with DiviTum® Thymidine Kinase 1 Activity

Abstract Background: CDK 4/6i have altered the therapeutic landscape of HR+, HER2- MBC, improving progression free and overall survival (PFS and OS) compared to endocrine therapy (ET) alone. Despite durable responses to CDK 4/6i in a large majority of patients, treatment response monitoring in this population has historically included numerous serial blood-based and imaging studies at frequent time points. There is a growing global interest in utilizing novel non-invasive biomarker-driven disease monitoring assessments to improve patient outcomes and reduce health care costs. Thymidine kinase 1 (TK1), a key cell-cycle regulated enzyme important for nucleotide metabolism during DNA synthesis, is regulated by the E2F pathway, downstream of CDK 4/6. Studies have shown that DiviTum® TK1 activity (TKa) may serve as both a prognostic and predictive biomarker of CDK 4/6i treatment response (McCartney et al, Clin Canc Res, 2020; Malorni et al, Eur J Cancer, 2022; Bagegni et al, Breast Cancer Res, 2017). Early TKa suppression within 2 weeks (wk) post CDK 4/6i therapy initiation is associated with improved PFS, suggesting a subgroup of patients who may be able to de-escalate imaging frequency. Elevated TKa at baseline and post CDK 4/6i may identify patients with CDK 4/6i-resistant disease and disease progression (PD) requiring early therapy modification. TK IMPACT is a prospective, single-arm trial designed to assess the impact of incorporation of DiviTum® TKa on a physician’s decision regarding subsequent timing of routine disease monitoring modalities in patients with advanced HR+, HER2- MBC receiving ET plus CDK 4/6i (NCT04968964). Methods: Blood sample collections will be analyzed using DiviTum® TKa at baseline (bl), wk 2, 4, 6, 8, and Q 4 wks thereafter beginning at wk 8 during the first 24-wk time period of study enrollment (+/- 3 days); followed by Q 12 wks thereafter, until PD or 36 months, whichever occurs first. Optional repeat TKa within 2-4 wks (+/-3 days) is permitted in case of rising TKa. Research blood (bl, wk 2, 12, 24, 48, and PD) and optional archival tumor tissue collection at diagnosis and PD will be obtained for correlatives. The investigator will record intended imaging modalities and timing prior to receipt of TKa, followed by documentation of any changes in imaging testing interval after receipt of TKa. Key eligibility criteria include postmenopausal women age ≥18 years with HR+, HER2- MBC, to initiate (Cohort 1) or are currently receiving (≤24 months, Cohort 2) any FDA approved first line ET plus CDK 4/6i with a life expectancy &amp;gt; 6 months. The primary endpoint is any physician-reported intended change in imaging testing interval post TKa by study cohort, within the first 48-wk period of study participation. Key secondary endpoints are concordance rate between TKa values and progression status at first on-study imaging and longitudinal TKa dynamics. Key exploratory endpoints include plasma and tumor tissue-based biomarkers of CDK 4/6i response and resistance. A total of 40 patients will be enrolled (n=20/Cohort). The expected change rate is 20% with a 95% Wilson confidence interval of 0.105~0.248 across all patients and if within each cohort, with a 95% Wilson confidence interval of 0.081~0.416 for N=20. N=40 allows the lower limit of the 95% CI &amp;gt; 10% and that of the N=20 in Cohort 1 to be ~10%, indicating some clinically meaningful influence of TKa progression on patient management. The study is open to accrual and has presently enrolled 5 patients. Citation Format: Nusayba A. Bagegni, Isabella Grigsby, Leslie Nehring, Jingqin Luo, Jennifer Powers Carson, David W. Gibson, Meghan Horvath, Katherine K. Clifton, Foluso O. Ademuyiwa, Rama Suresh, Ashley Frith, Andrew A. Davis, Lindsay L. Peterson, Ron Bose, Amy Williams, Mattias Bergqvist, Cynthia Ma. TK IMPACT: Treatment Monitoring of Hormone Receptor Positive (HR+), HER2 Negative (HER2-) Metastatic Breast Cancer (MBC) Patients Receiving CDK 4/6 Inhibitors (CDK4/6i) with DiviTum® Thymidine Kinase 1 Activity [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr OT3-11-01.

Detection of SARS-CoV-2 IgG antibodies and inflammatory cytokines in saliva-a pilot study.

The pandemic caused by SARS-CoV-2 virus continues to have a profound effect worldwide. However, COVID-19 induced oral facial manifestations have not been fully described. We conducted a prospective study to demonstrate feasibility of anti-SARS-CoV-2 IgG and inflammatory cytokine detection in saliva. Our primary objective was to determine whether COVID-19 PCR positive patients with xerostomia or loss of taste had altered serum or saliva cytokine levels compared to COVID-19 PCR positive patients without those oral symptoms. Our secondary objective was to determine the correlation between serum and saliva COVID-19 antibody levels. For cytokine analysis, saliva and serum were obtained from 17 participants with PCR-confirmed COVID-19 infection at three sequential time points, yielding 48 saliva samples and 19 paired saliva-serum samples from 14 of the 17 patients. For COVID-19 antibody analyses, an additional 27 paired saliva-serum samples from 22 patients were purchased. The saliva antibody assay had 88.64% sensitivity [95% Confidence Interval (CI) 75.44%, 96.21%] to detect SARS-CoV-2 IgG antibodies compared to serum antibody. Among the inflammatory cytokines assessed - IL-6, TNF-α, IFN-γ, IL-10, IL-12p70, IL-1β, IL-8, IL-13, IL-2, IL-5, IL-7 and IL-17A, xerostomia correlated with lower levels of saliva IL-2 and TNF-α, and elevated levels of serum IL-12p70 and IL-10 (p<0.05). Loss of taste was observed in patients with elevated serum IL-8 (p<0.05). Further studies are needed to construct a robust saliva-based COVID-19 assay to assess antibody and inflammatory cytokine response, which has potential utility as a non-invasive monitoring modality during COVID-19 convalescence.

The gestational age significantly affects peripheral perfusion index value in low-altitude areas.

The gestational age significantly affects peripheral perfusion index value in low-altitude areas.

Respiratory Monitoring During Mechanical Ventilation: The Present and the Future.

The increased application of mechanical ventilation, the recognition of its harms and the interest in individualization raised the need for an effective monitoring. An increasing number of monitoring tools and modalities were introduced over the past 2 decades with growing insight into asynchrony, lung and chest wall mechanics, respiratory effort and drive. They should be used in a complementary rather than a standalone way. A sound strategy can guide a reduction in adverse effects like ventilator-induced lung injury, ventilator-induced diaphragm dysfunction, patient-ventilator asynchrony and helps early weaning from the ventilator. However, the diversity, complexity, lack of expertise, and associated cost make formulating the appropriate monitoring strategy a challenge for clinicians. Most often, a big amount of data is fed to the clinicians making interpretation difficult. Therefore, it is fundamental for intensivists to be aware of the principle, advantages, and limits of each tool. This analytic review includes a simplified narrative of the commonly used basic and advanced respiratory monitors along with their limits and future prospective.