Urine Tenofovir Levels Strongly Correlate With Virologic Suppression in Patients With Human Immunodeficiency Virus on Tenofovir Alafenamide-Based Antiretroviral Therapy.

We found that urine tenofovir (TFV) levels >1500 ng/mL strongly predict virologic suppression among people with human immunodeficiency virus taking tenofovir alafenamide (odds ratio, 5.66; 95% confidence interval, 1.59-20.14; P = .007). This suggests an existing point-of-care assay developed for tenofovir disoproxil fumarate will support adherence monitoring for patients on all TFV-based antiretrovirals.

Drive-Through Anticoagulation Clinic During the COVID-19 Pandemic.

An innovative approach to anticoagulation management during the COVID-19 pandemic was used at our center that allowed patients to stay in their vehicle while our anticoagulation advanced practice registered nurse obtained blood for point-of-care international normalized ratio (INR) testing while education and counseling were completed. A significant improvement in the median percentage of INR within the therapeutic range was observed among the patients who used the drive-through clinic. A small group of patients improved compliance to anticoagulation monitoring. Clinical care models, such as this clinic approach may improve patient compliance and adherence to anticoagulation beyond the pandemic needs.

Bioluminescent Antibodies for Point-of-Care Diagnostics.

We introduce a general method to transform antibodies into ratiometric, bioluminescent sensor proteins for the no-wash quantification of analytes. Our approach is based on the genetic fusion of antibody fragments to NanoLuc luciferase and SNAP-tag, the latter being labeled with a synthetic fluorescent competitor of the antigen. Binding of the antigen, here synthetic drugs, by the sensor displaces the tethered fluorescent competitor from the antibody and disrupts bioluminescent resonance energy transfer (BRET) between the luciferase and fluorophore. The semisynthetic sensors display a tunable response range (submicromolar to submillimolar) and large dynamic range (ΔRmax >500 %), and they permit the quantification of analytes through spotting of the samples onto paper followed by analysis with a digital camera.

A non-enzymatic urine glucose sensor with 2-D photonic crystal hydrogel.

A novel polymerized crystalline colloidal array (PCCA) sensing material for the detection of urine glucose was developed by embedding a two-dimensional (2-D) polystyrene crystalline colloidal array (CCA) in 3-acrylamidophenylboronic acid (3-APBA)-functionalized hydrogel. After adjusting the cross-linker concentration, this material showed significant sensitivity for glucose under lab conditions, the particle spacing of the PCCA changed from 917 to 824 nm (93 nm) within 3 min as the glucose concentration increased from 0 to 10 mM, and the structural color of the PCCA changed from red through orange, to green, and finally, to cyan. In further experiments, this material was used to semi-quantitatively detect glucose in 20 human urine (HU) samples. Compared with the traditional dry-chemistry method, which was applied widely in clinical diagnosis, the PCCA method was more accurate and cost-effective. Moreover, this method can efficiently avoid the errors induced by most of the urine-interfering elements like vitamin C and ketone body. With a homemade portable optical detector, this low-cost intelligent sensing material can provide a more convenient and efficient strategy for the urine glucose detection in clinical diagnosis and point-of-care monitoring.

Rotational Thromboelastometry Values After On-Pump Cardiac Surgery - A Retrospective Cohort Study.

BACKGROUND: Viscoelastic coagulation monitoring is recommended for coagulation management after cardiac surgery, but optimum target values are poorly defined. AIMS: To determine "to-be-expected" values in rotational thromboelastometry (ROTEM) after heparin reversal, to correlate ROTEM parameters with fibrinogen levels and platelet count, and to estimate the effect of hemoglobin levels on these measurements. METHODS: We retrospectively analyzed 571 consecutive adult patients undergoing cardiac surgery with cardiopulmonary bypass from 12/2018 to 08/2020. ROTEM and conventional laboratory measurements were performed 5 to 10 minutes after protamine administration. RESULTS: Clotting times in EXTEM, INTEM, and FIBTEM were significantly prolonged (72.6%, 96.1%, and 31.8% above reference ranges, respectively). Clot firmness parameters in EXTEM and INTEM were relevantly reduced (7.9% to 14.4% and 9.1% to 32.3% below the reference ranges, respectively). There was an excellent linear correlation of FIBTEM amplitude after 10 min (A10) and of maximal clot firmness (MCF) with fibrinogen concentrations (r = .81 and .80). Areas under receiver operating characteristic (AUROC) for identifying hypofibrinogenemia <1.5 g/L were between .80 and .87. No effect of hematocrit was observed. We also found a linear correlation of EXTEM, INTEM, and EXTEM-FIBTEM at both A10 and MCF with platelet counts (.32 to .68). The AUROCs for identifying thrombocytopenia (<100,000/µL) were .79 to .84, and were greater for A10 than for MCF measurements (P=.074, .001, and <.001, respectively). CONCLUSIONS: "To-be-expected" ROTEM values after CPB are different from the published reference ranges. ROTEM parameters might allow for reliable estimation of fibrinogen level and platelet count without being influenced by hematocrit.

Warfarin Reversal With Four-Factor Prothrombin Complex Concentrate for Left Ventricular Assist Device Conversion Surgery Monitored by TEG6s: A Case Report.

Left ventricular assist devices (LVADs) require careful therapeutic anticoagulation with warfarin to prevent pump thrombosis. However, the best method to reverse warfarin for elective LVAD conversion surgery with massive bleeding remains unclear. We report the case of a 39-year-old Japanese man who was administered a four-factor prothrombin complex concentrate (4F-PCC) as warfarin reversal when he underwent conversion surgery from paracorporeal LVAD to implantable LVAD. 4F-PCC with co-administration of vitamin K reduced the international normalized ratio and R time in TEG6s (Haemonetics Corporation, USA) immediately. The effect was prolonged, and good hemostasis was achieved. 4F-PCC with vitamin K provided good hemostasis in our patient; therefore, 4F-PCC could be a useful tool for elective LVAD conversion surgery with expected massive bleeding and requiring immediate warfarin reversal.

A review of biosensor technologies for blood biomarkers toward monitoring cardiovascular diseases at the point-of-care.

Cardiovascular diseases (CVDs) cause significant mortality globally. Notably, CVDs disproportionately negatively impact underserved populations, such as those that are economically disadvantaged and often located in remote regions. Devices to measure cardiac biomarkers have traditionally been focused on large instruments in a central laboratory but the development of affordable, portable devices that measure multiple cardiac biomarkers at the point-of-care (POC) are needed to improve clinical outcomes for patients, especially in underserved populations. Considering the enormity of the global CVD problem, complexity of CVDs, and the large candidate pool of biomarkers, it is of great interest to evaluate and compare biomarker performance and identify potential multiplexed panels that can be used in combination with affordable and robust biosensors at the POC toward improved patient care. This review focuses on describing the known and emerging CVD biosensing technologies for analysis of cardiac biomarkers from blood. Initially, the global burden of CVDs and the standard of care for the primary CVD categories, namely heart failure (HF) and acute coronary syndrome (ACS) including myocardial infarction (MI) are discussed. The latest United States, Canadian and European society guidelines recommended standalone, emerging, and add-on cardiac biomarkers, as well as their combinations are then described for the prognosis, diagnosis, and risk stratification of CVDs. Finally, both commercial in vitro biosensing devices and recent state-of-art techniques for detection of cardiac biomarkers are reviewed that leverage single and multiplexed panels of cardiac biomarkers with a view toward affordable, compact devices with excellent performance for POC diagnosis and monitoring.

Peripheral Nerve Injury in Thoracic Surgery Detected by Automated Somatosensory Evoked Potential Monitoring.

Study Objective. Our objectives were to estimate the incidence of symptoms of peripheral nerve injury (sPNI) in thoracic surgical patients undergoing video-assisted thoracic surgery or open thoracotomy and to determine whether intraoperative somatosensory evoked potentials (SSEPs) waveform changes correlate with postoperative peripheral neuropathic symptoms. Methods. We conducted a prospective observational study in the operating room of a tertiary hospital. We measured SSEPs intraoperatively and assessed patients for sPNI postoperatively. Results. Forty-four patients consented. Six were excluded from analysis. We found that 42% (95% confidence interval [CI] = 26% to 57%) of patients undergoing thoracic surgery had significant changes in SSEP amplitude and latency. Furthermore, 16% (95% CI = 4% to 28%) of patients had new postoperative symptoms of sensory or motor deficits in an upper extremity. We calculated a sensitivity of 66.7% (95% CI = 29.0% to 100%) and a specificity of 50% (95% CI = 33% to 67.3%) for the identification of sPNI based on automated intraoperative SSEP changes. Conclusions. We identified the incidence of SSEP changes in thoracic surgery (42%) and the incidence of postoperative sPNI after thoracic surgery (16%). We identified a positive correlation between intraoperative SSEP changes and postoperative sPNI, which after multivariate analysis was not significant given the small sample size of the study. By the time sensory and/or motor changes are detected postoperatively, it may be too late to reverse the nerve damage. Future versions of the EPAD device could provide anesthesiologists a way to monitor for the development of sPNI, and make changes before a potential injury becomes permanent.

Invasive and non-invasive point-of-care testing and point-of-care monitoring of the hemoglobin concentration in human blood - how accurate are the data?

In this review, scientific investigations of point-of-care testing (POCT) and point-of-care monitoring (POCM) devices are summarized with regard to the measurement accuracy of the hemoglobin concentration. As a common basis, information according to the Bland and Altman principle [bias, limits of agreement (LOA)] as well as the measurement accuracy and precision are considered, so that the comparability can be mapped. These collected data are subdivided according to the manufacturers, devices and procedures (invasive and non-invasive). A total of 31 devices were identified. A comparability of the scientific investigations in particular was given for 23 devices (18 invasive and five non-invasive measuring devices). In terms of measurement accuracy, there is a clear leap between invasive and non-invasive procedures, while no discernible improvement can be derived in the considered time frame from 2010 to 2018. According to the intended use, strict specifications result from the clinical standards, which are insufficiently met by the systems. More stringent requirements can be derived both in the area of blood donation and in the treatment of patients.

Quantitative Measurement of Erythrocyte Aggregation as a Systemic Inflammatory Marker by Ultrasound Imaging: A Systematic Review.

This systematic review is aimed at answering two questions: (i) Is erythrocyte aggregation a useful biomarker in assessing systemic inflammation? (ii) Does quantitative ultrasound imaging provide the non-invasive option to measure erythrocyte aggregation in real time? The search was executed through bibliographic electronic databases CINAHL, EMB Review, EMBASE, MEDLINE, PubMed and the grey literature. The majority of studies correlated elevated erythrocyte aggregation with inflammatory blood markers for several pathologic states. Some studies used "erythrocyte aggregation" as an established marker of systemic inflammation. There were limited but promising articles regarding the use of quantitative ultrasound spectroscopy to monitor erythrocyte aggregation. Similarly, there were limited studies that used other ultrasound techniques to measure systemic inflammation. The quantitative measurement of erythrocyte aggregation has the potential to be a routine clinical marker of inflammation as it can reflect the cumulative inflammatory dynamics in vivo, is relatively simple to measure, is cost-effective and has a rapid turnaround time. Technologies like quantitative ultrasound spectroscopy that can measure erythrocyte aggregation non-invasively and in real time may offer the advantage of continuous monitoring of the inflammation state and, thus, may help in rapid decision making in a critical care setup.

Transfusion-Related Acute Lung Injury (TRALI) and Transfusion-Associated Circulatory Overload (TACO) in Liver Transplantation: A Case Report and Focused Review.

Liver transplantation (LT) is a complex procedure in a patient with multi-organ system dysfunction and coagulation defects. The surgical procedure involves dissection, major vessel manipulation, and pathophysiologic effects of graft storage and reperfusion. As a result, LT frequently involves significant hemorrhage. Subsequent massive transfusion carries high risk of transfusion-associated complications. Transfusion-related acute lung injury (TRALI) and transfusion-associated circulatory overload (TACO) are the leading causes of transfusion associated mortality. In this case report and focused review, we present data that suggest that patients undergoing liver transplantation may be at higher risk for TRALI and TACO than the general population. Anesthesiologists can play a role in decreasing these risks by increasing recognition and reporting of TRALI and TACO, using point of care testing with thromboelastography to guide and decrease transfusion, and considering alternatives to traditional blood products like solvent/detergent plasma.

Thromboelastrography (TEG) Is Still Relevant in the 21st Century as a Point-of-Care Test for Monitoring Coagulation Status in the Cardiac Surgical Suite.

Since their introduction into clinical practice in the early 1960s, viscoelastic point-of-care (POC) testing-thromboelastrography (TEG) and thromboelastrometry (ROTEM)-has become increasingly popular in intensive care units, operating rooms, and emergency room settings. As TEG has been an established POC viscoelastic testing modality for many years, there has been more research and analysis of its utility and ability to reduce transfusions in the general, cardiac, and liver surgical sectors compared with ROTEM. The role of TEG versus ROTEM has been greatly disputed, although both continue to be utilized in the cardiac suite to guide transfusion in cardiac surgery as these procedures produce a profoundly different form of bleeding compared to other surgical interventions.

Cardiopulmonary Bypass Without Heparin.

Due to familiarity, short half-life, ease of monitoring, and the availability of a reversal agent, heparin remains the anticoagulant of choice for cardiac operations requiring cardiopulmonary bypass (CPB). However, occasionally patients require CPB but should not receive heparin, most often because of acute or subacute heparin-induced thrombocytopenia (HIT). In these cases, if it is not feasible to wait for the disappearance of HIT antibodies, an alternative anticoagulant must be selected. A number of non-heparin anticoagulant options have been explored. However, current recommendations suggest the use of a direct thrombin inhibitor such as bivalirudin. This review describes the use of heparin alternatives for the conduct of CPB with a focus on the direct thrombin inhibitors.

The journey for adolescents and young adults with chronic conditions transitioning to adult care with successful warfarin management.

UNLABELLED: Health transition of youth from a child-centered care model to the adult model has been recognized to be of critical importance due to the increasing numbers of children now surviving chronic conditions. A formalized transition process is required adequately assess the AYA's readiness for transition and to move towards adult care. Indefinite warfarin therapy poses challenges as warfarin is a narrow therapeutic index drug that requires frequent monitoring and attentiveness to warfarin interactions and affects. OBJECTIVE: The objective of this study was to evaluate transition to adult care for AYAs requiring indefinite warfarin therapy within a structured self-management program. OUTCOME MEASURES: Results were compared between Phase 1 (enrollment to patient self-management) and Phase 2 (independent warfarin management) 6months following confirmation of transition to adult care. There was no statistical difference between outcome measures except INR testing frequency, and no adverse events. CONCLUSIONS: This transition process resulted in successful transition as measured by TTR and other clinical end-points from pediatric to adult care. Implementing a formal transition process for young adults with chronic health conditions that considers patient preferences motivates and empowers them over time to develop autonomy with warfarin self-management, results in successful transition and warfarin management.

EMPoWARed: Edmonton pediatric warfarin self-management study.

BACKGROUND: Patient self-management (PSM) in adults is safer and more cost effective than conventional management. Warfarin is a narrow therapeutic index drug with individual patient response to changes and frequently a long-term therapy. Children and their families are proposed to be able to effectively manage their child's warfarin therapy. Increased health related quality of life is highly associated with effective therapy in patients with chronic conditions. OBJECTIVES: The aim of this study is to evaluate the safety and efficacy of PSM over time including HRQOL and variables that may influence PFU success at PSM. PATIENTS/METHODS: Children and their family units (PFUs) current performing patient self-testing/monitoring for ≥ 3 months were enrolled in this cohort study. PFUs participated in comprehensive education on warfarin testing and management followed by an apprenticeship. Socio-demographic, clinical, and laboratory data were collected to evaluate safety and efficacy and health related quality of life. Outcomes were compared between the first 6 months on PSM (phase 1) and the last 6 months data collected on PSM (phase 2). RESULTS: Forty-two patients performed PSM for a median of 2.7 years (range: 1.1-6.2 years). Time in therapeutic range was 90% and 92.9% (p=0.30) in phases 1 and 2 respectively. All measures were strongly associated with improved heath related quality of life. PFUs socio-demographic status did not influence success at PSM. All PFUs maintained warfarin knowledge and INR testing competency. Warfarin dosing decision errors median 0 (range: 0-5, p=0.73) and a median 0 (range 0-4, p=0.55) per patient in phases 1 and 2 respectively. There were no adverse hemorrhagic or thrombotic events. CONCLUSIONS: Empowering PFUs to self-manage warfarin results in increased knowledge and understanding of their health condition, improved commitment to their health care and adherence to medication regimens and is demonstrated to be sustainable over time.

A 2014 Update on Coagulation Management for Cardiopulmonary Bypass.

Coagulopathy after cardiac surgery with cardiopulmonary bypass is a serious complication that may result in massive bleeding requiring transfusion of significant amounts of blood products, plasma, and platelets. In addition to increased patient morbidity and mortality it is associated with longer hospital stay and increased resource utilization. The current review discusses aspects in cardiopulmonary bypass-induced coagulopathy with emphasis on point-of-care testing and individualized "goal-directed" therapy in patients who develop excessive bleeding after cardiac surgery.