Continuous Blood Sampling Research Articles

Noise-aware dynamic image denoising and positron range correction for Rubidium-82 cardiac PET imaging via self-supervision

Rubidium-82 (82Rb) is a radioactive isotope widely used for cardiac PET imaging. Despite numerous benefits of 82Rb, there are several factors that limits its image quality and quantitative accuracy. First, the short half-life of 82Rb results in noisy dynamic frames. Low signal-to-noise ratio would result in inaccurate and biased image quantification. Noisy dynamic frames also lead to highly noisy parametric images. The noise levels also vary substantially in different dynamic frames due to radiotracer decay and short half-life. Existing denoising methods are not applicable for this task due to the lack of paired training inputs/labels and inability to generalize across varying noise levels. Second, 82Rb emits high-energy positrons. Compared with other tracers such as 18F, 82Rb travels a longer distance before annihilation, which negatively affect image spatial resolution. Here, the goal of this study is to propose a self-supervised method for simultaneous (1) noise-aware dynamic image denoising and (2) positron range correction for 82Rb cardiac PET imaging. Tested on a series of PET scans from a cohort of normal volunteers, the proposed method produced images with superior visual quality. To demonstrate the improvement in image quantification, we compared image-derived input functions (IDIFs) with arterial input functions (AIFs) from continuous arterial blood samples. The IDIF derived from the proposed method led to lower AUC differences, decreasing from 11.09% to 7.58% on average, compared to the original dynamic frames. The proposed method also improved the quantification of myocardium blood flow (MBF), as validated against 15O-water scans, with mean MBF differences decreased from 0.43 to 0.09, compared to the original dynamic frames. We also conducted a generalizability experiment on 37 patient scans obtained from a different country using a different scanner. The presented method enhanced defect contrast and resulted in lower regional MBF in areas with perfusion defects. Lastly, comparison with other related methods is included to show the effectiveness of the proposed method.

Postprandial Effects of Four Test Meals Containing Wholegrain Rye or Refined Wheat Foods on Circulating Incretins, Ghrelin, Glucose, and Inflammatory Markers

BackgroundHigh intake of whole grains has consistently been associated with reduced risk of obesity, coronary heart disease, and type 2 diabetes. Dietary interventions have shown beneficial metabolic effects of whole grain, but the metabolic response varies with different types of cereals. ObjectivesWe evaluate the metabolic effects of substituting refined wheat with wholegrain rye foods within a complex diet, examining day-long postprandial response of glucose-dependent insulinotropic peptide, (GIP), glucagon-like peptide-1 (GLP-1), ghrelin, glucose, and inflammatory biomarkers in overweight and obese individuals. MethodsTwenty-nine healthy adults, BMI 32 ± 9 kg/m2 were randomly assigned to three intervention days, separated by one-week washout. Participants adhered to a hypocaloric diet rich in wholegrain rye for one intervention and refined wheat for the second intervention and were randomized to either diet for the third intervention with continuous blood sampling. ResultsNo differences in GIP, GLP-1 or ghrelin levels were found between the diets when measured throughout the whole intervention day. GIP tAUC following the rye-based lunch was 31% (p < 0.05) lower compared with the wheat-based lunch and ghrelin concentrations were 29% (p < 0.05) lower after the rye-based dinner. Baseline HOMA-IR adjusted model, showed 61% (p = 0.015) lower whole-day GLP-1 and 40% (p = 0.03) lower GIP following the rye-based diet. Day-long glucose iAUC was 30% (p <0.001) lower following the rye-based diet and glycemic variability measured as SD reduced (−0.13 mmol/L p = 0.04). The rye-based diet vs refined wheat induced higher glycoprotein N-acetylation A by z-scores (0.36, p = 0.014). ConclusionsOverall, no day-long differences in gut hormone levels were observed, but the wholegrain rye-based vs refined wheat-based dinner showed lower postprandial ghrelin concentrations. The rye-based diet improved day-long glycemic control in individuals with overweight and obesity. Observations of diet-induced inflammation following whole-grain rye intake warrant further investigation. This study was prospectively registered at ClinicalTrials.gov (NCT05004584)https://clinicaltrials.gov/study/NCT05004584?locStr=Gothenburg,%20Sweden&country=Sweden&state=V%C3%A4stra%20G%C3%B6taland%20County&city=Gothenburg&distance=50&term=appetite&aggFilters=status:com&rank=1

Usefulness of an interprofessional work manual for perioperative glucose control of an artificial pancreas.

A closed-loop bedside-type artificial pancreas for perioperative glucose control has previously been introduced. However, artificial pancreas therapy was often interrupted due to continuous blood sampling failure. We developed an interprofessional work manual to reduce the interruption time of artificial pancreatic therapy for perioperative blood glucose control due to continuous blood sampling failure. This study aimed to investigate the usefulness of this manual. The manual consisted of the following sections: (1) the roles of the professionals in the preparation and management of the artificial pancreas, (2) how to address continuous blood sampling failure, and (3) checkpoints for interprofessional transfer of the artificial pancreas. We compared the results before the introduction of the manual and 2 years after the introduction of the manual. There were 35 and 37 patients in the Before and After groups, respectively. There were no significant differences in patient backgrounds between the two groups, although there was significantly less blood loss in the After group (1164 vs. 366 mL; p < 0.001). The mean artificial pancreas therapy and artificial pancreas therapy interruption times were 847 min and 20 min, respectively. Artificial pancreas therapy interruption time (34 vs. 8 min; p = 0.078) and time per interruption (24 vs. 4 min; p < 0.001) were significantly shorter in the After group than in the Before group. The interprofessional working manual was useful in reducing the artificial pancreatic therapy interruption time for perioperative glucose control.

Normoxic Management during Cardiopulmonary Bypass Does Not Reduce Cerebral Mitochondrial Dysfunction in Neonatal Swine.

Optimal oxygen management during pediatric cardiopulmonary bypass (CPB) is unknown. We previously demonstrated an increase in cortical mitochondrial reactive oxygen species and decreased mitochondrial function after CPB using hyperoxic oxygen management. This study investigates whether controlled oxygenation (normoxia) during CPB reduces cortical mitochondrial dysfunction and oxidative injury. Ten neonatal swine underwent three hours of continuous CPB at 34 °C (flow > 100 mL/kg/min) via cervical cannulation targeting a partial pressure of arterial oxygen (PaO2) goal < 150 mmHg (normoxia, n = 5) or >300 mmHg (hyperoxia, n = 5). The animals underwent continuous hemodynamic monitoring and serial arterial blood sampling. Cortical microdialysate was serially sampled to quantify the glycerol concentration (represents neuronal injury) and lactate-to-pyruvate ratio (represents bioenergetic dysfunction). The cortical tissue was analyzed via high-resolution respirometry to quantify mitochondrial oxygen consumption and reactive oxygen species generation, and cortical oxidized protein carbonyl concentrations were quantified to assess for oxidative damage. Serum PaO2 was higher in hyperoxia animals throughout CPB (p < 0.001). There were no differences in cortical glycerol concentration between groups (p > 0.2). The cortical lactate-to-pyruvate ratio was modestly elevated in hyperoxia animals (p < 0.03) but the values were not clinically significant (<30). There were no differences in cortical mitochondrial respiration (p = 0.48), protein carbonyls (p = 0.74), or reactive oxygen species generation (p = 0.93) between groups. Controlled oxygenation during CPB does not significantly affect cortical mitochondrial function or oxidative injury in the acute setting. Further evaluation of the short and long-term effects of oxygen level titration during pediatric CPB on cortical tissue and other at-risk brain regions are needed, especially in the presence of cyanosis.

Assessment of [18F]PI-2620 Tau-PET Quantification via Non-Invasive Automatized Image Derived Input Function

Purpose[18F]PI-2620 positron emission tomography (PET) detects misfolded tau in progressive supranuclear palsy (PSP) and Alzheimer’s disease (AD). We questioned the feasibility and value of absolute [18F]PI-2620 PET quantification for assessing tau by regional distribution volumes (VT). Here, arterial input functions (AIF) represent the gold standard, but cannot be applied in routine clinical practice, whereas image-derived input functions (IDIF) represent a non-invasive alternative. We aimed to validate IDIF against AIF and we evaluated the potential to discriminate patients with PSP and AD from healthy controls by non-invasive quantification of [18F] PET.MethodsIn the first part of the study, we validated AIF derived from radial artery whole blood against IDIF by investigating 20 subjects (ten controls and ten patients). IDIF were generated by manual extraction of the carotid artery using the average and the five highest (max5) voxel intensity values and by automated extraction of the carotid artery using the average and the maximum voxel intensity value. In the second part of the study, IDIF quantification using the IDIF with the closest match to the AIF was transferred to group comparison of a large independent cohort of 40 subjects (15 healthy controls, 15 PSP patients and 10 AD patients). We compared VT and VT ratios, both calculated by Logan plots, with distribution volume (DV) ratios using simplified reference tissue modelling and standardized uptake value (SUV) ratios.ResultsAIF and IDIF showed highly correlated input curves for all applied IDIF extraction methods (0.78 < r < 0.83, all p < 0.0001; area under the curves (AUC): 0.73 < r ≤ 0.82, all p ≤ 0.0003). Regarding the VT values, correlations were mainly found between those generated by the AIF and by the IDIF methods using the maximum voxel intensity values. Lowest relative differences (RD) were observed by applying the manual method using the five highest voxel intensity values (max5) (AIF vs. IDIF manual, avg: RD = -82%; AIF vs. IDIF automated, avg: RD = -86%; AIF vs. IDIF manual, max5: RD = -6%; AIF vs. IDIF automated, max: RD = -26%). Regional VT values revealed considerable variance at group level, which was strongly reduced upon scaling by the inferior cerebellum. The resulting VT ratio values were adequate to detect group differences between patients with PSP or AD and healthy controls (HC) (PSP target region (globus pallidus): HC vs. PSP vs. AD: 1.18 vs. 1.32 vs. 1.16; AD target region (Braak region I): HC vs. PSP vs. AD: 1.00 vs. 1.00 vs. 1.22). VT ratios and DV ratios outperformed SUV ratios and VT in detecting differences between PSP and healthy controls, whereas all quantification approaches performed similarly in comparing AD and healthy controls.ConclusionBlood-free IDIF is a promising approach for quantification of [18F]PI-2620 PET, serving as correlating surrogate for invasive continuous arterial blood sampling. Regional [18F]PI-2620 VT show large variance, in contrast to regional [18F]PI-2620 VT ratios scaled with the inferior cerebellum, which are appropriate for discriminating PSP, AD and healthy controls. DV ratios obtained by simplified reference tissue modeling are similarly suitable for this purpose.

Deep-learning-derived input function in dynamic [18F]FDG PET imaging of mice.

Dynamic positron emission tomography and kinetic modeling play a critical role in tracer development research using small animals. Kinetic modeling from dynamic PET imaging requires accurate knowledge of an input function, ideally determined through arterial blood sampling. Arterial cannulation in mice, however, requires complex, time-consuming and terminal surgery, meaning that longitudinal studies are impossible. The aim of the current work was to develop and evaluate a non-invasive, deep-learning-based prediction model (DLIF) that directly takes the PET data as input to predict a usable input function. We first trained and evaluated the DLIF model on 68 [18F]Fluorodeoxyglucose mouse scans with image-derived targets using cross validation. Subsequently, we evaluated the performance of a trained DLIF model on an external dataset consisting of 8 mouse scans where the input function was measured by continuous arterial blood sampling. The results showed that the predicted DLIF and image-derived targets were similar, and the net influx rate constants following from Patlak modeling using DLIF as input function were strongly correlated to the corresponding values obtained using the image-derived input function. There were somewhat larger discrepancies when evaluating the model on the external dataset, which could be attributed to systematic differences in the experimental setup between the two datasets. In conclusion, our non-invasive DLIF prediction method may be a viable alternative to arterial blood sampling in small animal [18F]FDG imaging. With further validation, DLIF could overcome the need for arterial cannulation and allow fully quantitative and longitudinal experiments in PET imaging studies of mice.

Overcoming the clinical challenges of traditional ayahuasca: a first-in-human trial exploring novel routes of administration of N,N-Dimethyltryptamine and harmine

Recently, the Amazonian plant medicine “ayahuasca”—containing the psychedelic compound N,N-dimethyltryptamine (DMT) and numerous β-carboline alkaloids, such as harmine—has been suggested to exhibit beneficial effects in patients with affective and other mental health disorders. Although ayahuasca ingestion is considered safe, its pharmacokinetics/pharmacodynamics and tolerability profile pose some challenges and may limit the clinical applicability in vulnerable patient populations. While overdosing and the admixture of intolerable plant constituents may explain some of the common adverse reactions, the peroral route of administration may represent another relevant source of gastro-intestinal intolerabilities and unpredictable pharmacokinetics across users. To overcome these challenges, the present work aimed at creating ayahuasca-analogue formulations with improved pharmacokinetics and tolerability profiles. To this end, we developed peroral formulas and compared them with parenteral formulas specifically designed to circumvent the gastro-intestinal tract. In more detail, peroral administration of a capsule (containing purified DMT and harmine) was tested against a combined administration of an oromucosal harmine tablet and an intranasal DMT spray at two dose levels in an open-label within-subject study in 10 healthy male subjects. Pharmacokinetic and pharmacodynamic profiles were assessed by means of continuous blood sampling, vital sign monitoring, and psychometric assessments. Common side effects induced by traditional herbal ayahuasca such as nausea, vomiting, and diarrhea were significantly attenuated by our DMT/harmine formulations. While all preparations were well tolerated, the combined buccal/intranasal administration of harmine and DMT yielded substantially improved pharmacokinetic profiles, indicated by significantly reduced variations in systemic exposure. In conclusion, the combined buccal/intranasal administration of harmine and DMT is an innovative approach that may pave the way towards a safe, rapid-acting, and patient-oriented administration of DMT/harmine for the treatment of affective disorders.Clinical Trial Registration:clinicaltrials.gov, identifier NCT04716335

The Predictive Value of Circulating Exosomal PD-L1 in Cervical Cancer Immunotherapy

Programmed death ligand 1 (PD-L1) expression was wildly used as a predictor of immune Check-Point Inhibitors (ICIs) efficiency. However, emerging results showed that PD-L1 was of great heterogeneity in sampling time and site. Recently, some studies found that exosomal PD-L1(ExoPD-L1) was related to ICIs response. In this study, we aimed to explore the predictive value of ExoPD-L1 in ICIs treatment of cervical cancer (CC) for the first time. A total of 40 primarily diagnosed CC patients who accepted radical radiotherapy (RT) from March 2021 to October 2022 were included. The consecutive tumor sample were collected before and during RT. Another 37 advanced CC patients who accepted ICIs combination therapy from June 2020 to October 2022 were enrolled in this study. Blood samples were collected from each participant before and during treatment. Exosomes were derived by differential centrifugation, which was further identified by Western blot (WB) (CD9/TSG101/Calnexin), transmission electron microscope analysis and nanoparticle tracking analysis. ExoPD-L1 detection was conducted by enzyme-linked immuno-sorbent assay (ELISA). The knockout of PD-L1 was conducted via CRISPR/Cas9 assay and the overexpress of PD-L1 was conducted by lentiviral transfection. CD8+ T cells were extracted from murine spleen by CD8+ T Cell Isolation Kit. Immune cells and cytokines markers were detected by multicolor flow cytometry. The consecutive detection of PD-L1 showed a dynamic change during RT. Compared with the level before RT, PD-L1 expression elevated in most patients (87.5%, 35/40) after RT. And the responders (n = 18) had elevated ExoPD-L1 level at the first two circles in the ICIs combination therapy (P<0.001). Whereas the level of pre-treatment ExoPD-L1 couldn't stratified clinical responders and non-responders (P = 0.181). The median follow-up time was 14.13 months. The mPFS in increased group vs. decreased group: not reach vs.11.02 months (P = 0.025, HR: 0.218, 0.052-0.913). Continuous blood sampling of mice models also found that effective therapeutic intervention could increase ExoPD-L1 in the early stage. The combination of exosome inhibitor GW4869 and anti-PD-1 further inhibited tumor growth. Mice were injected with external ExoPD-L1OE and ExoPD-L1KO. The results showed that ExoPD-L1OE suppressed body immunity and promoted tumor growth. The results of flow cytometry showed that ExoPD-L1OE inhibited CD8+ T cells from releasing interferon-and granzyme B. And ExoPD-L1OE also suppressed the CD8+ T cells proliferation in murine spleen. The coculture of CD8+ T cells and exosomes in vitro also confirmed the above conclusion. Compared with unstable and impressionable tumoral PD-L1, ExoPD-L1 seems to be better predictor for the efficacy of immunotherapy in CC, which was with easy accessibility and continuation. Exosome PD-L1 played an immunosuppressive role by inhibiting the proliferation and functional factor release of CD8+ T cell.

Circulating exosomal PD-L1 to predict response with immunotherapy in patients with advanced cervical cancer.

e17514 Background: Programmed death ligand 1 (PD-L1) expression was wildly used to predict immune Check-Point Inhibitors (ICIs) efficiency. However, emerging results showed that PD-L1 was of great heterogeneity in sampling time and site. Recently, some studies found that exosomal PD-L1(ExoPD-L1) was related to ICIs response. In this study, we aimed to explore the predictive value of ExoPD-L1 in ICIs treatment of cervical cancer (CC) for the first time. Methods: 40 primarily diagnosed CC patients who accepted radical radiotherapy (RT) were included. The consecutive tumor sample were collected before and during RT. Another 37 advanced CC patients who accepted ICIs combination therapy were collected. Blood samples were collected from each participant before and during treatment. Exosomes were derived by differential centrifugation, which was further identified by Western blot (CD9/TSG101/Calnexin), transmission electron microscope analysis and nanoparticle tracking analysis. ExoPD-L1 detection was conducted by enzyme-linked immuno-sorbent assay (ELISA). The knockout of PD-L1 was conducted via CRISPR/Cas9 assay and the overexpress of PD-L1 was conducted by lentiviral transfection. CD8+ T cells were extracted from murine spleen by CD8+ T Cell Isolation Kit. Immune cells and cytokines markers were detected by multicolor flow cytometry. Results: The consecutive detection of PD-L1 showed a dynamic change during RT. Compared with the level before RT, PD-L1 expression elevated in most patients (87.5%, 35/40) after RT. And the responders (n = 18) had elevated ExoPD-L1 level at the first two circles in the ICIs combination therapy (P &lt; 0.001). Whereas the level of pre-treatment ExoPD-L1 couldn’t stratified clinical responders and non-responders (P = 0.181). The median follow-up time was 14.13 months. The mPFS in increased group vs. decreased group: not reach vs.11.02 months (P = 0.025, HR: 0.218, 0.052-0.913). Continuous blood sampling of mice models also found that effective therapeutic intervention could increase ExoPD-L1 in the early stage. The combination of exosome inhibitor GW4869 and anti-PD-1 further inhibited tumor growth. Mice were injected with external ExoPD-L1OE and ExoPD-L1KO. The results showed that ExoPD-L1OE suppressed body immunity and promoted tumor growth. The results of flow cytometry showed that ExoPD-L1OE inhibited CD8+ T cells from releasing interferon-γand granzyme B. And ExoPD-L1OE also suppressed the CD8+ T cells proliferation in murine spleen. The coculture of CD8+ T cells and exosomes in vitro also confirmed the above conclusion. Conclusions: Compared with unstable and impressionable tumoral PD-L1, ExoPD-L1 seems to be better predictor for the efficacy of immunotherapy in CC, which was with easy accessibility and continuation. Exosome PD-L1 played an immunosuppressive role by inhibiting the proliferation and functional factor release of CD8+ T cell.

Image-derived input functions from dynamic 15O–water PET scans using penalised reconstruction

BackgroundQuantitative positron emission tomography (PET) scans of the brain typically require arterial blood sampling but this is complicated and logistically challenging. One solution to remove the need for arterial blood sampling is the use of image-derived input functions (IDIFs). Obtaining accurate IDIFs, however, has proved to be challenging, mainly due to the limited resolution of PET. Here, we employ penalised reconstruction alongside iterative thresholding methods and simple partial volume correction methods to produce IDIFs from a single PET scan, and subsequently, compare these to blood-sampled input curves (BSIFs) as ground truth. Retrospectively we used data from sixteen subjects with two dynamic 15O-labelled water PET scans and continuous arterial blood sampling: one baseline scan and another post-administration of acetazolamide.ResultsIDIFs and BSIFs agreed well in terms of the area under the curve of input curves when comparing peaks, tails and peak-to-tail ratios with R2 values of 0.95, 0.70 and 0.76, respectively. Grey matter cerebral blood flow (CBF) values showed good agreement with an average difference between the BSIF and IDIF CBF values of 2% ± and a coefficient of variation (CoV) of 7.3%.ConclusionOur results show promising results that a robust IDIF can be produced for dynamic 15O–water PET scans using only the dynamic PET scan images with no need for a corresponding MRI or complex analytical techniques and thereby making routine clinical use of quantitative CBF measurements with 15O–water feasible.

Machine learning-based approach reveals essential features for simplified TSPO PET quantification in ischemic stroke patients

IntroductionNeuroinflammation evaluation after acute ischemic stroke is a promising option for selecting an appropriate post-stroke treatment strategy. To assess neuroinflammation in vivo, translocator protein PET (TSPO PET) can be used. However, the gold standard TSPO PET quantification method includes a 90 min scan and continuous arterial blood sampling, which is challenging to perform on a routine basis. In this work, we determine what information is required for a simplified quantification approach using a machine learning algorithm. Materials and MethodsWe analyzed data from 18 patients with ischemic stroke who received 0–90 min [18F]GE-180 PET as well as T1-weigted (T1w), FLAIR, and arterial spin labeling (ASL) MRI scans. During PET scans, five manual venous blood samples at 5, 15, 30, 60, and 85 min post injection (p.i.) were drawn, and plasma activity concentration was measured. Total distribution volume (VT) was calculated using Logan plot with the full dynamic PET and an image-derived input function (IDIF) from the carotid arteries. IDIF was scaled by a calibration factor derived from all the measured plasma activity concentrations. The calculated VT values were used for training a random forest regressor. As input features for the model, we used three late PET frames (60–70, 70–80, and 80–90 min p.i.), the ASL image reflecting perfusion, the voxel coordinates, the lesion mask, and the five plasma activity concentrations. The algorithm was validated with the leave-one-out approach. To estimate the impact of the individual features on the algorithm’s performance, we used Shapley Additive Explanations (SHAP). Having determined that the three late PET frames and the plasma activity concentrations were the most important features, we tested a simplified quantification approach consisting of dividing a late PET frame by a plasma activity concentration. All the combinations of frames/samples were compared by means of concordance correlation coefficient and Bland-Altman plots. ResultsWhen using all the input features, the algorithm predicted VT values with high accuracy (87.8 ± 8.3%) for both lesion and non-lesion voxels. The SHAP values demonstrated high impact of the late PET frames (60–70, 70–80, and 80–90 min p.i.) and plasma activity concentrations on the VT prediction, while the influence of the ASL-derived perfusion, voxel coordinates, and the lesion mask was low. Among all the combinations of the late PET frames and plasma activity concentrations, the 70–80 min p.i. frame divided by the 30 min p.i. plasma sample produced the closest VT estimate in the ischemic lesion. ConclusionReliable TSPO PET quantification is achievable by using a single late PET frame divided by a late blood sample activity concentration.

To Evaluate the Effect between Normal Saline and Heparin Solution in Arterial Line Flushing on Platelet Count – A Cross Sectional Study

Introduction: Arterial catheters are widely used in intensive care units for continuous blood pressure monitoring and blood sampling. The patency of these lines is maintained by continuous flushing, usually with the addition of the anticoagulant heparin to the flushing solution. Normal saline solution can maintain patency of arterial and central venous pressure monitoring catheters. Aim of the Study: The aim of this study was to evaluate the effect between normal saline and heparin solution in arterial line flushing on platelet count. Methods: This was a prospective cross- sectional study conducted in the Department of Cardiac surgery of National Institute of Cardiovascular Disease (NICVD), Sher-E-Bangla Nagar, Dhaka, Bangladesh during the period from July 2016 to June 2017. This study included sixty patients who underwent single valve replacement surgery and shifted to the ICU with arterial line catheter. The patients who fulfilled the inclusion criteria were divided into two groups- Group A (with heparin solution) and Group B (with normal saline). Result: In total 60 patients from both the groups completed the study. In our study we found the mean ± SD of age among group A &amp; B was (36.3±6.7) &amp; (35.7±10.3) respectively. We found the mean± SD of platelet count at 1st POD was (206530±64441) &amp; (212543±48768); at 3rd POD was (226517±60185) &amp; (245957±52826); at 7th POD was (240517±57379) &amp; (257713±53655); at 14th POD was (245850±52680) &amp; (244337±56796) in Group A &amp; B respectively. Conclusion: In our study we didn’t find any statistically significant difference regarding the patients’ demographic characteristics and there were no statistically significant difference of platelet counts between Group A and Group B at preoperative period, post pump, 1st POD, 2nd POD, 3rd POD, 4th POD, 7th POD and 14th POD.

Dynamic Continuous Blood Extraction from Rat Heart via Noninvasive Microdialysis Technique.

Dynamic analysis of blood components is of great importance in understanding cardiovascular diseases and their related diseases, such as myocardial infarction, arrhythmia, atherosclerosis, cardiogenic pulmonary edema, pulmonary embolism, and cerebral embolism. At the same time, it is urgent to break through the continuous heart blood sampling technique in live rats to evaluate the effectiveness of distinctive ethnic medicine therapy. In this study, a blood microdialysis probe was implanted in the right jugular vein of rats in a precise and noninvasive surgical procedure. Cardiac blood samples were then collected at a rate of 2.87 nL/min to 2.98 mL/min by connecting to an online microdialysis sample collection system. Even more momentously, the acquired blood samples can temporarily be stored in microdialysis containers at 4 °C. The microdialysis-based online continuous blood collection program from rat heart has greatly guaranteed the quality of blood samples, advancing and invigorating the scientific rationality of the research on systemic cardiovascular diseases and evaluating ethnomedicine therapy from the perspective of hematology.

Non-Invasive Measurement of Arterial pH During Cardiopulmonary Bypass

Blood pH is an essential parameter to determine the patient's acid-base status during cardiopulmonary bypass. To date, continuous pH measurement is usually done by continuous blood sampling using an expensive disposable sensor. This paper shows the feasibility of measuring arterial pH from the partial pressure of carbon dioxide (PaCO2) using arterial blood gas analysis. Further, the effect of hyperglycemia on pH estimation is included to show the necessity of combining glucose monitoring with PaCO2 monitoring.&#x0D; 245 blood samples from patients who underwent cardiopulmonary bypass were used. Patients with renal failure were excluded from the study. In this study, three groups of samples were included, A: all blood samples, B: blood samples with glucose ≤ 200 mg/dL, and C: blood samples with glucose &gt; 200 mg/dL. A linear approximation based on the least-squares criterion was used to derive the best-fit equation.&#x0D; Our results indicate that there is no significant difference among the models. Further, there is a significant association between arterial pH and PaCO2 with a p-value &lt; 0.001 and RMSE of about 0.04. The present findings highlighted that arterial pH could be estimated from PaCO2. Additionally, hyperglycemia did not affect the hypothesis of the general relationship between pH and PaCO2.

235-OR: Sustained QTc Prolongation during Recovery from Hypoglycemia in Patients with Type 1 Diabetes

Hypoglycemia and increased glycemic variability have been associated with cardiac arrhythmias and sudden cardiac death. We investigated cardiac repolarization during acute hypoglycemia followed by recovery to hyperglycemia or euglycemia in patients with type 1 diabetes. In a randomized crossover study, patients with type 1 diabetes (N=24, (mean±SD) age 53±years, HbA1c 7.5±0.8% [57.6±8.9 mmol/mol], diabetes duration 23±14 years, BMI 25.7± 3.1 kg/m2) underwent two clamps with three steady-state phases: 1) a hyperinsulinemic-euglycemic phase for 45 minutes, 2) a hyperinsulinemic-hypoglycemic phase for 60 minutes, and 3) a recovery phase in hyperglycemia (clamp A) or euglycemia (clamp B) for 60 minutes. Continuous ECG (Holter) monitoring and blood samples for counterregulatory hormones and plasma potassium were obtained. Linear mixed models were used to assess the impact of hypoglycemia and recovery to hyperglycemia vs. euglycemia on cardiac repolarization. Heart rate-corrected QT (QTc) (Fridericia’s formula) progressively increased from baseline (mean (95% CI) , clamp A: 415 msec (409;421) ; clamp B: 418 msec (412;424)) during hypoglycemia on both clamp days (∆mean (95% CI) , clamp A: 21 msec (11;31) ; clamp B: 22 msec (12;31)) . In the recovery phase, QTc remained increased during hyperglycemia and euglycemia (17 msec (11;21) vs. 14 msec (10;20)) with no difference in change between recovery to hyperglycemia compared to euglycemia (3 msec (-6;11) , P=0.5442) . No significant changes from baseline were observed in QTc dispersion (heterogeneity of myocardial repolarization) during hypoglycemia or in the recovery phases. We conclude that clinically significant QTc prolongations during insulin-induced hypoglycemia remain during a 60-minute recovery period independently of recovery to hyperglycemia or euglycemia in patients with type 1 diabetes. Thus, vulnerability for serious cardiac arrhythmias and sudden cardiac death may extend beyond a hypoglycemic event itself. Disclosure C.R.Andreasen: None. A.Andersen: n/a. P.G.Hagelqvist: None. J.V.Lauritsen: None. S.Engberg: Employee; Novo Nordisk A/S. J.J.Holst: Advisory Panel; Novo Nordisk, Board Member; Antag Therapeutics, Bainan Biotech. U.Pedersen-bjergaard: Advisory Panel; Novo Nordisk A/S, Sanofi. F.K.Knop: Advisory Panel; Boehringer Ingelheim International GmbH, Eli Lilly and Company, Merck Sharp &amp; Dohme Corp., Novo Nordisk, Sanofi, ShouTi, Zucara Therapeutics, Consultant; AstraZeneca, Eli Lilly and Company, Novo Nordisk, Pharmacosmos A/S, Sanofi, ShouTi, Zealand Pharma A/S, Zucara Therapeutics, Research Support; AstraZeneca, Novo Nordisk, Sanofi, Zealand Pharma A/S, Speaker's Bureau; AstraZeneca, Bayer AG, Boehringer Ingelheim International GmbH, Eli Lilly and Company, Novo Nordisk, Sanofi, Stock/Shareholder; Antag Therapeutics. T.Vilsbøll: Consultant; AstraZeneca, Bristol-Myers Squibb Company, Eli Lilly and Company, Gilead Sciences, Inc., GlaxoSmithKline plc., Merck Sharp &amp; Dohme Corp., Mundipharma, Novo Nordisk, Sun Pharmaceutical Industries Ltd. Funding Danish Diabetes Academy (NNF17SA0031406)

Effect of a sulforaphane supplement on muscle soreness and damage induced by eccentric exercise in young adults: A pilot study.

ObjectiveExcessive exercise increases the production of reactive oxygen species in skeletal muscles. Sulforaphane activates nuclear factor erythroid 2‐related factor 2 (Nrf2) and induces a protective effect against oxidative stress. In a recent report, sulforaphane intake suppressed exercise‐induced oxidative stress and muscle damage in mice. However, the effect of sulforaphane intake on delayed onset muscle soreness after eccentric exercise in humans is unknown. We evaluated the effect of sulforaphane supplement intake in humans regarding the delayed onset muscle soreness (DOMS) after eccentric exercise.Research Methods & ProceduresTo determine the duration of sulforaphane supplementation, continuous blood sampling was performed and NQO1 mRNA expression levels were analyzed. Sixteen young men were randomly divided into sulforaphane and control groups. The sulforaphane group received sulforaphane supplements. Each group performed six set of five eccentric exercise with the nondominant arm in elbow flexion with 70% maximum voluntary contraction. We assessed muscle soreness in the biceps using the visual analog scale, range of motion (ROM), muscle damage markers, and oxidative stress marker (malondialdehyde; MDA).ResultsSulforaphane supplement intake for 2 weeks increased NQO1 mRNA expression in peripheral blood mononuclear cells (PBMCs). Muscle soreness on palpation and ROM were significantly lower 2 days after exercise in the sulforaphane group compared with the control group. Serum MDA showed significantly lower levels 2 days after exercise in the sulforaphane group compared with the control group.ConclusionOur findings suggest that sulforaphane intake from 2 weeks before to 4 days after the exercise increased NQO1, a target gene of Nrf2, and suppressed DOMS after 2 days of eccentric exercise.

P24.13 Circulating Tumor Cells Predict Prognosis Following First-Generation EGFR-TKI Treatment in EGFR- and TP53-Mutant Non-Small Cell Lung Cancer

For advanced non-small cell lung cancer (NSCLC) with EGFR mutations, first-generation EGFR-TKIs have become the first-line standard treatment. Co-mutation of EGFR and TP53 may be indicated EGFR-TKI resistance, shorter PFS and OS. This study isolates and quantifies circulating tumor cells (CTCs) and evaluates patient prognosis before and after first-line treatment with EGFR-TKIs in advanced NSCLC with EGFR and TP53 mutation. Patients with advanced NSCLC with EGFR and TP53 mutation were treated with a first-generation EGFR-TKI using a standard daily dose. Continuous blood samples were collected at baseline (CTCs-d0) and 28 days (CTCs-d28), and the isolation by CTCBIOPSY® was used to detect CTCs. The CTCs results were divided into favorable (< 5 CTCs) and unfavorable (≥ 5 CTCs) groups. The median progression-free survival (PFS) of patients in the favorable group was significantly longer at baseline and after 28 days of treatment compared to those in the unfavorable group (p = 0.0055; p = 0.0003). After treatment, the PFS of patients with reduced CTCs was significantly better than those with no significant change in CTCs (p = 0.014). Patients with CTCs-d0 ≥ 5 and CTCs-d28 ≥ 5 had significantly lower PFS when compared to those with CTCs-d0 < 5 and CTCs-d28 < 5, respectively. This study confirmed for the first time that CTC count is closely correlated with prognosis in EGFR- and TP53-mutant advanced NSCLC following first-line treatment with first-generation EGFR-TKIs.

Validation and optimisation of an automatic blood sampler for preclinical positron emission tomography research in domestic pigs.

In preclinical positron emission tomography animal studies, continuous blood sampling is used to measure the time course of the activity concentration in arterial blood. However, pigs have hypercoagulable blood that tends to clot inside plastic tubes. We tested several tube materials and lengths and the use of three-way connectors. We validated set-ups for automated blood sampling with and without blood recirculation that could run for 90 minutes without problematic clots and without any evidence of emboli formation during necropsy.

Acute hypoglycemia and risk of cardiac arrhythmias in insulin-treated type 2 diabetes and controls.

ObjectiveHypoglycemia is associated with an increased risk of cardiovascular disease including cardiac arrhythmias. We investigated the effect of hypoglycemia in the setting of acute glycemic fluctuations on cardiac rhythm and cardiac repolarization in insulin-treated patients with type 2 diabetes compared with matched controls without diabetes.DesignA non-randomized, mechanistic intervention study.MethodsInsulin-treated patients with type 2 diabetes (n = 21, age (mean ± s.d.): 62.8 ± 6.5 years, BMI: 29.0 ± 4.2 kg/m2, HbA1c: 6.8 ± 0.5% (51.0 ± 5.4 mmol/mol)) and matched controls (n = 21, age: 62.2 ± 8.3 years, BMI 29.2 ± 3.5 kg/m2, HbA1c: 5.3 ± 0.3% (34.3 ± 3.3 mmol/mol)) underwent a sequential hyperglycemic and hypoglycemic clamp with three steady-states of plasma glucose: (i) fasting plasma glucose, (ii) hyperglycemia (fasting plasma glucose +10 mmol/L) and (iii) hyperinsulinemic hypoglycemia (plasma glucose < 3.0 mmol/L). Participants underwent continuous ECG monitoring and blood samples for counterregulatory hormones and plasma potassium were obtained.ResultsBoth groups experienced progressively increasing heart rate corrected QT (Fridericia’s formula) interval prolongations during hypoglycemia ((∆mean (95% CI): 31 ms (16, 45) and 39 ms (24, 53) in the group of patients with type 2 diabetes and controls, respectively) with similar increases from baseline at the end of the hypoglycemic phase (P = 0.43). The incidence of ventricular premature beats increased significantly in both groups during hypoglycemia (P = 0.033 and P < 0.0001, respectively). One patient with type 2 diabetes developed atrial fibrillation during recovery from hypoglycemia.ConclusionsIn insulin-treated patients with type 2 diabetes and controls without diabetes, hypoglycemia causes clinically significant and similar increases in cardiac repolarization that might increase vulnerability for serious cardiac arrhythmias and sudden cardiac death.

Cerebral blood flow measurements with 15O-water PET using a non-invasive machine-learning-derived arterial input function

Cerebral blood flow (CBF) can be measured with dynamic positron emission tomography (PET) of 15O-labeled water by using tracer kinetic modelling. However, for quantification of regional CBF, an arterial input function (AIF), obtained from arterial blood sampling, is required. In this work we evaluated a novel, non-invasive approach for input function prediction based on machine learning (MLIF), against AIF for CBF PET measurements in human subjects. Twenty-five subjects underwent two 10 min dynamic 15O-water brain PET scans with continuous arterial blood sampling, before (baseline) and following acetazolamide medication. Three different image-derived time-activity curves were automatically segmented from the carotid arteries and used as input into a Gaussian process-based AIF prediction model, considering both baseline and acetazolamide scans as training data. The MLIF approach was evaluated by comparing AIF and MLIF curves, as well as whole-brain grey matter CBF values estimated by kinetic modelling derived with either AIF or MLIF. The results showed that AIF and MLIF curves were similar and that corresponding CBF values were highly correlated and successfully differentiated before and after acetazolamide medication. In conclusion, our non-invasive MLIF method shows potential to replace the AIF obtained from blood sampling for CBF measurements using 15O-water PET and kinetic modelling.