Venous Plasma Research Articles

1296-P: Comparison of Fingerstick and Venous Plasma Glucose in the Ugandan Diabetes in Low-Resource Populations Study

As Africa is experiencing the most rapid rise in the world of type 2 diabetes (T2D), identifying feasible, accurate ways to measure glucose is imperative. While venous glucose (ven-glucose) is recommended, cost and lack of access to pre-analytical processing often rules out this option. Fingerstick measurement of capillary glucose (fs-glucose) is a potential alternative. But data on the correlation between fs-glucose and ven-glucose are scant. Hence OGTT were performed in 512 Ugandans (Male: 46% (234/512), age: 43±17y (mean±SD) enrolled in the Diabetes in Low Resource Populations Study with fs-glucose (Contour Plus Glucometer) and ven-glucose (Glucokinase Method, Roche Cobas 6000) obtained at 0h and 2h. To determine correlation, bias and levels of agreement, Pearson’s correlations and Bland Altman analyses were performed. T2D, preT2D and normal glucose tolerance occurred in 2% (9/512), 18% (92/512) and 80% (411/512), resp. At 0h, fs-glucose and ven-glucose were modestly correlated (r= 0.56) (Fig) with a modest bias for lower glucose by fs-glucose 0.28 mmol/L (95% CI: 0.23, -0.34). At 2h, glucose, fs-glucose and ven-glucose were highly correlated (r=0.92) (Fig) with modest bias for higher glucose by fs-glucose 0.60 mmol/L (95% CI: 0.53, 0.66) mmol/L. Overall, fs-glucose may be an alternative to ven-glucose in Africans where the prevalence of undetected T2D is high and resources are limited. Disclosure A.J.Niwaha: None. A.E.Sumner: None. H.Nkabura: None. R.J.Mukasa: None. N.Mubiru: None. P.A.Balungi: None. I.Sekitoleko: None. B.Mpairwe: None.

#3827 BICARBONATE PROFILING IN HEMODIALYSIS: MATHEMATICAL MODELING OF DATA FROM A CLINICAL TRIAL

Abstract Background and Aims During hemodialysis (HD), bicarbonate and other bases are added to the dialysis fluid to correct chronic acidosis that may develop in kidney-impaired patients, increasing plasma bicarbonate concentration to physiological levels. Previous studies have shown that both exceedingly high and low post-dialysis bicarbonate concentrations are associated with adverse clinical outcomes; however, no clear guidelines for the prescription of bicarbonate concentration in the dialysis fluid are available. Data from a recent controlled clinical trial, carried out at the Department of Nephrology, Dialysis and Internal Medicine, Medical University of Warsaw (Poland), were used to identify transport parameters of a mathematical model of acid-base homeostasis in HD patients, as the first step in the implementation of a tool to optimize bicarbonate profiling during HD. Method The study was carried out in 20 chronic patients, undergoing thrice weekly 4-hr HD. The patients underwent three treatment regimens: A) constant dialysis fluid bicarbonate concentration (HCO3,D) equal to 35 mEq/L; B) HCO3,D decreasing from 35 to 30 mEq/L after 2 hrs; C) HCO3,D increasing from 30 to 35 mEq/L after 2 hrs. The patients were divided in two cohorts: for the first (n = 11) treatment schedule was: treatment A during the first and third week, B during the second week and C during the fourth week. For the second cohort (n = 9) treatment C was carried out during the second week and treatment B during the fourth. Data were collected only during the second and third sessions of the week, and acid-base composition was determined using a blood gas analyzer. The mathematical model describes the transport of bicarbonate and dissolved CO2 from dialysis fluid to the patient and can predict changes in the acid-base equilibrium of arterial and venous plasma and erythrocytes, interstitial fluid, and tissue cells, using mass transport equations. The dialysances for bicarbonate (KHCO3) and dissolved CO2 (KCO2) were estimated via least square minimization. Results No significant difference was found comparing patients in the two cohorts, or comparing sessions of the same week. Pre-dialysis plasma bicarbonate, pH, or CO2 partial pressure (PCO2) were significantly lower for treatment B compared to treatment A. Average plasma bicarbonate concentrations for the different treatments are shown in Figure 1 for data and model simulations. Table 1 reports the average values of the estimated parameters for week. No statistically significant difference was found between sessions, cohorts, or treatments. The model fitted bicarbonate data with an average error of 2.5 ± 1.4%, and PCO2 with an error of 4.5 ± 3.6%. Simulations of mixed-venous blood, interstitial fluid, and tissue cells concentrations showed a similar response to different treatments as in arterial blood. Conclusion The model accurately describes plasma bicarbonate data with high accuracy regardless of the treatment conditions. The parameters estimated showed considerable variability between treatments (less so between the sessions of the same week), but without statistical significance. The model can be used to simulate the effect of dialysate bicarbonate profiling on acid-base equilibrium in HD patients.

18F]DPA-714: Effect of co-medications, age, sex, BMI and TSPO polymorphism on the human plasma input function.

We aimed to assess the effect of concomitant medication, age, sex, body mass index and 18-kDa translocator protein (TSPO) binding affinity status on the metabolism and plasma pharmacokinetics of [18F]DPA-714 and their influence on the plasma input function in a large cohort of 201 subjects who underwent brain and whole-body PET imaging to investigate the role of neuroinflammation in neurological diseases. The non-metabolized fraction of [18F]DPA-714 was estimated in venous plasma of 138 patients and 63 healthy controls (HCs; including additional arterial sampling in 16 subjects) during the 90min brain PET acquisition using a direct solid-phase extraction method. The mean fraction between 70 and 90min post-injection ([18F]DPA-71470-90) and corresponding normalized plasma concentration (SUV70-90) were correlated with all factors using a multiple linear regression model. Differences between groups (arterial vs venous measurements; HCs vs patients; high- (HAB), mixed- (MAB) and low-affinity binders (LAB); subjects with vs without co-medications, females vs males were also assessed using the non-parametric Mann-Whitney or Kruskal-Wallis ANOVA tests. Finally, the impact of co-medications on the brain uptake of [18F]DPA-714 at equilibrium was investigated. As no significant differences were observed between arterial and venous [18F]DPA-71470-90 and SUV70-90, venous plasma was used for correlations. [18F]DPA-71470-90 was not significantly different between patients and HCS (59.7 ± 12.3% vs 60.2 ± 12.9%) despite high interindividual variability. However, 47 subjects exhibiting a huge increase or decrease of [18F]DPA-71470-90 (up to 88% or down to 23%) and SUV70-90 values (2-threefold) were found to receive co-medications identified as inhibitors or inducers of CYP3A4, known to catalyse [18F]DPA-714 metabolism. Comparison between cortex-to-plasma ratios using individual input function (VTIND) or population-based input function derived from untreated HCs (VTPBIF) indicated that non-considering the individual metabolism rate led to a bias of about 30% in VT values. Multiple linear regression model analysis of subjects free of these co-medications suggested significant correlations between [18F]DPA-71470-90 and age, BMI and sex while TSPO polymorphism did not influence the metabolism of the radiotracer. [18F]DPA-714 metabolism fell with age and BMI and was significantly faster in females than in males. Whole-body PET/CT exhibited a high uptake of the tracer in TSPO-rich organs (heart wall, spleen, kidneys…) and those involved in metabolism and excretion pathways (liver, gallbladder) in HAB and MAB with a strong decrease in LAB (-89% and -85%) resulting in tracer accumulation in plasma (4.5 and 3.3-fold increase). Any co-medication that inhibits or induces CYP3A4 as well as TSPO genetic status, age, BMI and sex mostly contribute to interindividual variations of the radiotracer metabolism and/or concentration that may affect the input function of [18F]DPA-714 and consequently its human brain and peripheral uptake. INFLAPARK, NCT02319382, registered December 18, 2014, retrospectively registered; IMABIO 3, NCT01775696, registered January 25, 2013, retrospectively registered; INFLASEP, NCT02305264, registered December 2, 2014, retrospectively registered; EPI-TEP, EudraCT 2017-003381-27, registered September 24, 2018.

Introduction of an electrochemical point-of-care assay for quantitative determination of paracetamol in finger-prick capillary whole blood samples.

Measuring venous plasma paracetamol concentrations is time- and resource-consuming. We aimed to validate a novel electrochemical point-of-care (POC) assay for rapid paracetamol concentration determinations. Twelve healthy volunteers received 1 g oral paracetamol, and its concentrations were analysed 10 times over 12 h for capillary whole blood (POC), venous plasma (high-performance liquid chromatography tandem mass spectrometry (HPLC-MS/MS)), and dried capillary blood (HPLC-MS/MS). At concentrations >30 μM, POC showed upward biases of 20% (95% limits of agreement [LOA] -22 to 62) and 7% (95% LOA -23 to 38) compared with venous plasma and capillary blood HPLC-MS/MS, respectively. There were no significant differences between mean concentrations for the paracetamol elimination phase. Upward biases in POC compared with venous plasma HPLC-MS/MS were likely due to higher paracetamol concentrations in capillary blood than in venous plasma and to faulty individual sensors. The novel POC method is a promising tool for paracetamol concentration analysis.

Effects of Short-Term Sodium Nitrate versus Sodium Chloride Supplementation on Energy and Lipid Metabolism during High-Intensity Intermittent Exercise in Athletes

The aim of this study was to investigate the possible effects of chronic nitrate supplementation on the metabolites of energy metabolism during high-intensity, high-volume intermittent training (HIHVT). In this placebo-controlled double-blind study, 17 participants exercised 3 times a week on a cycle ergometer. Sodium nitrate or sodium chloride as the placebo was supplemented daily at 8.5 mg/kg body weight for 10 days. The training exercise consisted of a warm-up, a 45-min interval period, and a post-exercise period. Oxygen uptake, respiratory exchange ratio, and various parameters were measured in the venous blood and plasma. During training, the oxygen uptake and respiratory exchange ratio did not differ between the nitrate and the placebo group. Venous plasma concentrations of nitrate and nitrite were significantly increased in the nitrate group (p < 0.001 and p = 0.007, respectively). Triglyceride concentrations were significantly lower in the nitrate group than in the placebo group (p = 0.010). The concentration of free fatty acids in the plasma did not change upon nitrate supplementation and no significant differences were observed in the contribution of fat to energy metabolism during exercise. An increase in plasma ammonia concentration was observed in the nitrate group during and after exercise (p = 0.048). Metabolites of energy-rich phosphates did not differ between the nitrate and chloride groups, suggesting no improvement in efficiency through the supplemented nitrate. It was concluded that nitrate supplementation did not reduce oxygen uptake and adenosine triphosphate resynthesis by hydrolysis or through creatine kinase activity during high-intensity, high-volume intermittent exercise. Although, lipid metabolism as well as amino acid metabolism might be affected by nitrate supplementation during HIHVT.

INHIBITION OF AT1 RECEPTOR PARTIALLY PREVENTS ENDOVASCULAR ETHANOL INJECTION INDUCED ACUTE PULMONARY HYPERTENSION AND SECONDARY PULMONARY ARTERY REMODELING

Objective: Ethanol can induce acute pulmonary hypertension (APH) during endovascular sclerotherapy and embolization. We aimed to examine whether the inhibition of the AT1 receptor can prevent this pathological phenomenon and assess its related mechanisms. Design and method: A total of 40 male swine (age, approximately six months) were selected and performed with absolute ethanol endovascular injection (jugular vein). Saline was used as the negative control. Preventive administration of losartan was conducted orally for 3 consecutive days before operations. Pulmonary arterial pressure (PAP), femoral arterial pressure (FAP), and heart rate (HR) were monitored during procedures. Venous plasma and fresh pulmonary artery (PA) tissue of 32 swine were harvested immediately after the operation. The remaining eight swine were kept and sacrificed one-month after the operations, and PA tissues were harvested for paraffin embedding procedures. Protein level was detected by Western blotting and ELISA, whereas qRT-PCR was used in mRNA detection. H & E staining and immunohistochemistry (IHC) were conducted to evaluate histopathology. Results: Ethanol injection elevated PAP in all swine. The concentration of renin-angiotensin system (RAS) ligands was elevated in plasma (all P < 0.0001) but not in PA. The level of oxidative stress increased in both plasma and PA. MRNA level of AT1R (P < 0.01, 95% CI: 0.251 to 1.006), not AT2R increased in PA. Losartan failed to inhibit APH after all sessions of ethanol injection, and partially reversed the ethanol-induced PA remodeling (1. H & E staining presented abnormal morphology of PA; 2. CD31 IHC staining indicated the intimal hyperplasia; 3. a-SMA IHC staining suggested the pathomorphology of smooth muscle cells; 4. TNF-a IHC staining showed the infiltration of immune cells). The P38 MAPK was activated after ethanol injection and could be inhibited by losartan (P < 0.01, 95% CI: -0.391 to -0.164). Ethanol also promoted the translocation of the P40-PHOX/P47-PHOX/P67-PHOX complex and the activation of NOX, which was independent from RAS. Conclusions: Endovascular ethanol injection can induce AEPAP mainly by activating RAS and P38 MAPK signaling. Losartan can partially prevent AEPAP and vascular remodeling owing to the promotion of NOX activity by ethanol.

The impact of inter-laboratory glucose bias on the diagnosis of gestational diabetes mellitus: Comparison of common automated central laboratory methods

Background and aimsThe diagnosis of gestational diabetes mellitus (GDM) is based exclusively on glucose measurements, which are highly influenced by pre-analytical and analytical factors. Therefore, poor agreement across laboratories may affect the prevalence of GDM. We aimed to determine the inter-laboratory bias of glucose measurements and the impact on GDM prevalence. Material and methodsA prospective cohort study of women (n = 110) referred for second-trimester GDM diagnostics using a 75 g oral glucose tolerance test. Maternal glucose was assessed from venous plasma at fasting, 1 h and 2 h. Venous blood were collected in Fluoride Citrate tubes and frozen. Samples were analyzed at five central laboratories using four different automated glucose Hexokinase methods and GDM prevalence was evaluated according to WHO2013 diagnostic criteria. ResultsMaximum inter-laboratory bias was 0.19, 0.30 and 0.27 mmol/L in fasting, 1 h and 2 h samples, respectively. GDM prevalence ranged 30.0–41.1% across laboratories. ConclusionInter-laboratory bias for mean venous glucose was low and within desirable limits. Nonetheless, the impact on GDM prevalence was considerable, which may inappropriately affect clinical practice.

Oxidation‑reduction potential parameters worsen following intraarterial therapy in patients with reduced collateral circulation and middle cerebral artery occlusions.

Collateral circulation is important for cerebral perfusion in acute ischemic strokes. Monitoring the oxidation-reduction potential (ORP) may be useful to assess collateral status or treatment efficacy. The objectives of the present study were to determine if the ORP was associated with collateral circulation status in middle cerebral artery (MCA) occlusions and to identify patterns in the ORP and the collateral circulation status among patients treated with intraarterial therapy (IAT) over time. The present pilot study was nested within a prospective cohort study measuring the ORP of the peripheral venous plasma of stroke patients. The population included in the present study were patients with MCA (M1/M2) occlusions. Two ORP parameters were examined: Static ORP (sORP; mV), indicating oxidative stress, and capacity ORP (cORP; µC), indicating antioxidant reserves. Collateral status was retrospectively graded using Miteff's system as good (grade 1) or reduced (grade 2/3). Comparisons were made between collateral status groups (reduced vs. good collaterals) in all patients, within a subset including only patients who received IAT, and between thrombolysis in cerebral infraction scale score (TICI) groups (0-2a vs. 2b/3). The Fisher's exact test, Student's t-test and Wilcoxon tests were used (α<0.20). The 19 patients were categorized based on their collaterals: Good collaterals (53%) and reduced collaterals (47%). The baseline characteristics were similar with the exception that the patients with good collaterals had a lower international normalized ratio (P=0.12) and were more likely to have a stroke on the left side (P=0.18) or to have a mismatch (P=0.05). The admission sORP values were comparable (169.5 vs. 164.2 mV; P=0.65), as was admission cORP (P=0.73). When considering only the patients who received IAT (n=12), admission sORP (P=0.69) and cORP (P=0.90) were also statistically similar. On day 2, after IAT, both groups experienced a worsening in ORP measures; however, the patients with good collaterals had a significantly lower sORP (169.4 vs. 203.5 mV; P=0.02) and a higher cORP (0.2 vs. 0.1 µC; P=0.002) compared with the patients with reduced collaterals. Neither sORP nor cORP were significantly different between TICI score groups on admission or on day 2. Upon discharge, patients with a TICI of 2b-3 had a significantly better sORP (P=0.03) and cORP (P=0.12) compared with those with a TICI of 0-2a. In conclusion, upon patient admission, the ORP parameters were not significantly different between the collateral circulation status groups for MCA occlusions. The ORP parameters worsened after IAT regardless of the collateral circulation status; however, after IAT, on day 2, patients with good collaterals experienced less oxidative stress (sORP) and had higher antioxidant reserves (cORP) than patients with reduced collaterals.

Results from healthy donors for novel point-of-care high-sensitivity troponin test

Abstract Funding Acknowledgements Type of funding sources: None. Background/Introduction This study evaluates healthy donor values of a novel high-sensitivity troponin test, an 8-minute whole blood assay performed with fingerstick or Lithium-heparin samples using a handheld sized platform designed for Point-of-Care or in-lab measurements. In accordance with the Fourth Universal Definition of Myocardial Infarction, whole blood 99th percentile upper reference limits (URLs) and 50th percentile (median) values for healthy individuals were characterised per gender; values were established for fingerstick, venous whole blood, and plasma. Purpose To determine 99th percentile URLs for hs-cTnI in healthy donors as myocardial injury cut-off for use in clinical trials and clinical practice. The median values were determined to confirm high-sensitivity performance in all matrices. Methods Whole blood from consented healthy subjects, 22 to 85 years (n=810), were collected across 5 clinical sites. Subjects taking cardiac history/medications or having abnormal hemoglobin A1c, NT-proBNP, and eGFR values were excluded. hs-cTnI values were determined in capillary (fingerstick), Li-Heparin venous whole blood, and venous Li-Heparin plasma matrices. Sex-specific and overall 99th percentile URLs using the recommended non-parametric approach and median values for each sample matrix were determined. Results Statistical outliers were eliminated by the Dixon-Reed test, prior to calculating the 99th percentile and median values. There was no significant difference between the three sample types. The median results are tabulated below: as expected, the female values are lower than the male values (p &amp;lt;0.01). These data additionally show that &amp;gt;50% of results exceed the assays limit of detection [ref .1] for all matrices, confirming this assay is a high-sensitive assay for troponin-I. Conclusion The novel hs-cTnI system is the first that demonstrates high-sensitivity cTnI performance in fingerstick, whole blood and plasma matrices. Quality measurements in all three matrices translates to use with confidence in emergency department and other diagnosis and triage settings. Hence, the data presented here are of relevance to current and future studies and clinical implementation of this device. Table 1: median hs-cTnI values in healthy subject, % of subjects above LoD (limit of detection) and %CV at 99th URL.

МЕТАБОЛИЧЕСКИЙ ПРОФИЛЬ СВОБОДНЫХ АМИНОКИСЛОТ ПРИ БЕРЕМЕННОСТИ, ОСЛОЖНЕННОЙ COVID-19

Background. The unexpected emergence and rapid spread around the world of a new coronavirus infection COVID-19, with a large number of deaths, has shown the importance of developing the methods for predicting a severe course of viral infections, creating diagnostic tests, preventive vaccines and drugs that act on key factors in the course and progression of the disease. Clinical studies examining metabolomic changes in pregnant women with COVID-19 infection are virtually non-existent. Purpose of the study. To study the features of the metabolic profile of free amino acids during pregnancy complicated by COVID-19. Material and methods. The concentrations of free amino acids and their derivatives in the blood plasma of 86 women were studied. The main group included 51 pregnant women with a confirmed diagnosis of COVID-19; the control group was composed of 35 somatically healthy women with uncomplicated pregnancies. The analysis of amino acids and their derivatives was carried out using high performance liquid chromatography. Results. During the development of COVID-19 infection, protein catabolism predominates, as evidenced by an increase in the concentration of 28 amino acids and their derivatives in venous blood plasma. We revealed a statistically significant increase in the concentration of cysteine, homocysteine, γ-glutamylcysteine, phosphoserine, cysteine sulfinate, aspartate, homocysteate, glutamate, asparagine, serine, threonine, 1-methylhistidine, glycine, citrulline, arginine, alanine, symmetric dimethylarginine, asymmetric dimethylarginine, β-aminobutyric acid, γ-aminobutyric acid, tyrosine, valine, methionine, phenylalanine, leucine, isoleucine, lysine, ornithine in pregnant women with a new coronavirus infection as compared to the patients in the control group. Conclusion. The study of the features of the metabolic profile of free amino acids in pregnant women with a new coronavirus infection will enable us to identify additional biomarkers of the severity of the disease and predict the course of the disease in patients during the gestation period.

Effect of acute tauroursodeoxycholic acid ingestion on microvascular function in men and women

The endoplasmic reticulum is a multipurpose organelle found in most human cells, including endothelial and smooth muscle cells of blood vessels. It plays a key role in posttranslational folding of new proteins and reprocessing of misfolded or damaged proteins. Under certain conditions, the accumulation of unfolded proteins can trigger a quality control system (i.e., the unfolded protein response) that restores protein homeostasis in the endoplasmic reticulum. However, the unfolded protein response can simultaneously augment the formation of reactive oxygen species and inflammatory mediators which can induce vascular dysfunction. Despite our understanding of the relation between endoplasmic reticulum stress and vascular dysfunction in animal and human models, the sex-dependent influence of the endoplasmic reticulum on microvascular function has not been explored. Therefore, we tested the hypothesis that compared with placebo, acute ingestion of tauroursodeoxycholic acid (TUDCA) would improve microvascular function to the same extent in men and women. Twelve young healthy adults (6 women, 26 ± 5 yrs) were studied ~8 hours following ingestion of a placebo or 1,500 mg of TUDCA, a chemical chaperone that inhibits endoplasmic reticulum stress. Experiments were randomized, counterbalanced, and separated by at least 7 days. Venous plasma TUDCA and its taurine conjugated form, ursodeoxycholic acid, were measured for both conditions via high-performance liquid chromatography. Microvascular function was assessed using post-occlusive reactive hyperemia (Doppler ultrasound) and was normalized to mean arterial blood pressure. Compared with placebo (men, 13 ± 15 ng/ml; women, 6 ± 2 ng/ml), TUDCA ingestion increased plasma concentrations (men, 80 ± 43 ng/ml; women, 140 ± 93 ng/ml; P = 0.05). Similarly, compared with placebo (men, 13 ± 14 ng/ml; women, 7 ± 4 ng/ml), plasma ursodeoxycholic acid increased following TUDCA ingestion (men, 666 ± 237 ng/ml; women, 559± 458 ng/ml; P &lt; 0.01). Plasma TUDCA and ursodeoxycholic acid concentrations did not vary between sexes (both P &gt; 0.4). Peak vascular conductance did not differ between placebo and TUDCA conditions ( P = 0.7), an effect that did not vary between men and women (men: placebo, 4.1 ± 1.1 ml/min/mmHg vs. TUDCA, 4.1 ± 1.1 ml/min/mmHg; women: placebo, 3.2 ± 1.1 ml/min/mmHg vs. TUDCA, 3.0 ± 1.1 ml/min/mmHg; P = 0.6). Likewise, reactive hyperemia area under the curve did not differ between placebo and TUDCA conditions ( P = 0.5), nor did it vary by sex ( P = 0.2). Contrary to our hypothesis, these data suggest that acute ingestion of tauroursodeoxycholic acid does not alter microvascular function in young healthy men and women. UNTHSC Seed Grant This is the full abstract presented at the American Physiology Summit 2023 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Abstract #1397695: Use of Continuous Glucose Monitoring to Solve the Mystery of Pseudohypoglycemia

Hypoglycemia (glucose < 55 mg/dL) is uncommon in people without diabetes. Routine monitoring of blood glucose in hospitalized patients usually is performed by fingerstick point of care (POC) glucose testing via glucometer as a measure of capillary whole-blood glucose, correlating with venous plasma glucose. Pseudohypoglycemia is a consideration when POC glucose is low but plasma blood glucose is normal range. It can occur in the setting of impaired peripheral perfusion, such as in patients with Raynaud’s disease, shock, or peripheral vascular disease (PVD). A 63-year-old female was admitted for evaluation of uncontrolled hypertension. Her medical history was significant for previous myocardial infarction, atrial fibrillation, and heart failure with preserved ejection fraction. She had no history of Raynaud's phenomenon, diabetes (HbA1C 5.1%), or known PVD. During hospitalization, she had symptoms of anxiety, diaphoresis, tremors, nausea, forgetfulness, dizziness. POC glucose was 37 mg/dL and the patient was promptly treated with IV dextrose, negating a blood draw for a confirmatory venous plasma glucose. Several similar episodes occurred, even while on dextrose infusion prompting a hypoglycemia laboratory work-up. Off of dextrose, her POC glucose dropped to <50 mg/dL with insulin 97.7 uIU/mL, C-peptide 12.3 ng/mL and proinsulin of 77 pmol/L. However venous glucose was 173 ng/mL and thought to reflect treatment with dextrose prior to the blood draw. A second time, POC glucose was <50 ng/mL with insulin 48.9 uIU/mL and C-peptide 6.0 ng/mL which could support hyperinsulinemia but, again, venous plasma glucose was normal (113 mg/dL). Anti-diabetic medication and insulin antibody screening were negative. A continuous glucose monitoring system (CGMS) was placed on her abdomen to provide alternative peripheral glucose data. The patient manifested glucoses of 32/15/21 mg/dL by glucometer while simultaneous CGMS values were 110/126/156 mg/dL, confirming pseudohypoglycemia. In nondiabetic patients, hypoglycemia fulfilling Whipple’s triad be documented prior to initiating the complex evaluation for causes of hypoglycemia. Our patient is unusual because she did not have usual causes of pseudohypoglycemia such as Raynaud’s disease, diabetes, shock, or PVD. The inaccuracy of POC glucose measurements in patients with impaired microperfusion should be considered when the data are incongruent, as this can cause unnecessary investigations and prolonged length of stay. Should alternative blood glucose monitoring be required in these patients, CGM is a valuable technology.

Development and Application of a Physiologically Based Pharmacokinetic Model for Diclazuril in Broiler Chickens.

Withdrawal periods for diclazuril in broilers have traditionally been determined through regression analysis. However, over the last two decades, the physiologically based pharmacokinetic (PBPK) model has gained prominence as a predictive tool for veterinary drug residues, which offers an alternative method for establishing appropriate withdrawal periods for veterinary drugs. In this current study, a flow-limited PBPK model was developed to predict diclazuril concentrations in broilers following long-duration administration via medicated feed and water. This model consists of nine compartments, including arterial and venous plasma, lung, muscle, skin + fat, kidney, liver, intestine contents, and the rest of the body compartment. Physiological parameters such as tissue weights (Vcxx) and blood flow (Qcxx) were gathered from published studies, and tissue/plasma partition coefficients (Pxx) were calculated through the area method or parameter optimization. Published diclazuril concentrations were compared to the predicted values, indicating the accuracy and validity of the model. The sensitivity analysis showed that parameters associated with cardiac output, drug absorption, and elimination significantly affected diclazuril concentrations in the muscle. Finally, a Monte Carlo analysis, consisting of 1000 iterations, was conducted to calculate the withdrawal period. Based on the Chinese MRL values, we calculated a withdrawal period of 0 days for both recommended dosing regimens (through mediated water and feed at concentrations of 0.5-1 mg/L and 1 mg/kg, respectively). However, based on the European MRLs, longer periods were determined for the mediated feed dosing route. Our model provides a foundation for scaling other coccidiostats and poultry species.

Evaluating the Clinical Accuracy of a Non-invasive Single-Fasting-Calibration Glucometer in Patients with Diabetes: A Multicentre Study.

The aim of this study was to evaluate the stability and accuracy of glucose measurements determined using the metabolic heat conformation (MHC)-based non-invasive glucometer in a multicentre, self-controlled clinical trial. This device is the first to obtain a medical device registration certificate awarded by the National Medical Products Administration of China (NMPA). The multicentre clinical study was conducted at three sites and enrolled 200 subjects whose glucose was measured with a non-invasive glucometer (the Contour Plus blood glucose monitoring system) and by venous plasma glucose (VPG) measurements, in a fasted state and at 2 and 4h after meals. Based on both the non-invasive and VPG measurements, 93.9% (95% confidence interval 91.7-95.6%) of the blood glucose (BG) values fell within consensus error grid (CEG) zones A + B. The measurements obtained in a fasted state and at 2h after meals were more accurate, with 99.0% and 97.0% of the BG values, respectively, falling within zones A + B. Compared to those subjects who received insulin, the proportion of values in zones A + B and the correlation coefficients were 3.1% and 0.0596 higher, respectively. The accuracy of the non-invasive glucometer was influenced by the level of insulin resistance calculated by the homeostatic model assessment method, which had a correlation coefficient with the mean absolute relative difference of - 0.1588 (P = 0.0001). The MHC-based non-invasive glucometer assessed in the present study demonstrates generally high stability and accuracy in the glucose monitoring of people with diabetes. The calculation model needs to be further explored and optimised for patients with different diabetes subtypes, levels of insulin resistance and insulin secretion capacity. ChiCTR1900020523.

Sodium depletion and secondary hyperaldosteronism in outpatients with an ileostomy: a cross-sectional study

Objective Patients with an ileostomy may experience postoperative electrolyte derangement and dehydration but are presumed to stabilise thereafter. We aimed to investigate the prevalence of sodium depletion in stable outpatients with an ileostomy and applied established methods to estimate their fluid status. Methods We invited 178 patients with an ileostomy through a region-wide Quality-of-Life-survey to undergo outpatient evaluation of their sodium and fluid status. The patients delivered urine and blood samples, had bioelectrical impedance analysis performed and answered a questionnaire regarding dietary habits. Results Out of 178 invitees, 49 patients with an ileostomy were included; 22 patients (45%, 95% CI, 31–59%) had unmeasurably low urinary sodium excretion (<20 mmol/L), indicative of chronic sodium depletion, and 26% (95% CI, 16–41%) had plasma aldosterone levels above the reference value. Patients with unmeasurably low urinary sodium excretion had low estimated glomerular filtration rates (median 76, IQR 63–89, mL/min/1.73m2) and low venous blood plasma CO2 (median 24, IQR 21–26, mmol/L), indicative of chronic renal impairment and metabolic acidosis. Bioelectrical impedance analysis, plasma osmolality, creatinine and sodium values were not informative in determining sodium status in this population. Conclusion A high proportion of patients with an ileostomy may be chronically sodium depleted, indicated by absent urinary sodium excretion, secondary hyperaldosteronism and chronic renal impairment, despite normal standard biochemical tests. Sodium depletion may adversely affect longstanding renal function. Future studies should investigate methods to estimate and monitor fluid status and aim to develop treatments to improve sodium depletion and dehydration in patients with an ileostomy. IMPACT AND PRACTICE RELEVANCE STATEMENT Sodium depletion in otherwise healthy persons with an ileostomy was identified in a few publications from the 1980s. The magnitude of the problem has not been demonstrated before. The present study quantifies the degree of sodium depletion and secondary hyperaldosteronism in this group, and the results may help guide clinicians to optimise treatment. Sodium depletion is easily assessed with a urine sample, and sequelae may possibly be avoided if sodium depletion is detected early and treated. This could ultimately help increase the quality of life in patients with an ileostomy.

Gestational diabetes mellitus: state of art

Gestational diabetes mellitus (GDM) is a disease characterized by hyperglycemia, first established during pregnancy, while the concentration of venous plasma glucose should not exceed 6.9 mmol/l. As a rule, after childbirth, the disease regresses, but it does not pass without a trace for either the mother or the child. The consequences of gestational diabetes include an increased risk of cardiovascular diseases in the mother and type 2 diabetes, as well as diabetic fetopathy of the fetus and complications during pregnancy and childbirth: the threat of termination of pregnancy, premature birth, preeclampsia, polyhydramnios, high frequency of operative delivery and birth trauma. There is also a long-term risk of developing obesity, diabetes and cardiovascular diseases in a child. Gestational diabetes affects approximately 16.5% of pregnant women worldwide, an increase in the incidence is predicted due to an increase in the percentage of obese women. Gestational diabetes mellitus is a complication of gestation that is not easily diagnosed and poorly predicted, and therefore potentially threatening to any pregnancy, requiring, given the list of perinatal and long – term consequences for mother and child, pre-gravidar prevention, thorough diagnosis and mandatory treatment with permanent control of glycemia levels, ketonuria and instrumental monitoring: cardiotcography and ultrasound. A competent approach to pregnancy planning, the implementation of a screening program for GDM and timely correction in case of its detection is the key to the health of a woman and her unborn child.

Laboratory rationale for dose reduction anticoagulant for thrombosis complicing treatment patients with hemoblastosis on the background of chemioinduced thrombocytopenia

Purpose of the study: To substantiate the minimum hemostatic threshold for platelet count, which regulates the anticoagulant therapy of thrombosis against the background of induced thrombocytopenia in children with malignant neoplasms. Material and research methods: 23 patients (group 1) with hemorrhagic syndrome caused by thrombocytopenia (less than 50∙109/l) were examined. The control group consisted of 21 patients (group 2) with a similar diagnosis, platelet count less than 150∙109/l, who did not have bleeding. All examined patients with hemoblastoses had signs of febrile neutropenia. Additionally, under the conditions of a bench experiment, dilutions of platelet donor plasma were prepared with a platelet content of 5.0×109/l, 10.0×109/l, 20.0×109/l, 30.0×109/l, 40.0×109/L, 50.0×109/L, 60.0×109/L, 70.0×109/L, 80.0×109/L, 90.0×109/L, 100.0×109 /l, 200.0×109/l. Platelets were counted in peripheral blood for each sample using an XN-3000 hematology analyzer (manufactured by Sysmex GmbH, Japan) by the impedance method using original reagents (SysmexGmbH). The endogenous thrombin potential (ETP) in patients' platelet plasma was determined by the Hemker method on a Fluoroskanascent fluoroscan manufactured by Thermo Electron Corporation (Maastricht, Netherlands) using reagent kits from Thrombinoscop eBV. Research results: Between the content of platelets in whole blood and EPT of platelet plasma of patients with hemoblastoses, a relationship was revealed, which is reflected by the regression equation: y = 15.1356 + (0.0745∙ x), where y is the content of platelets in the blood (109/l), and x - EPT nM/l∙min in venous blood plasma. The minimum threshold value of EPT of platelet plasma, which provides hemostasis, 250 nM/l∙min, corresponded to the minimum platelet content of 30.0∙109/l in the blood of FN patients. Decrease in the content of platelets in donor plasma less than 20×109/l led to a decrease in EPT less than 250 nM/l•min. Between the EPT generated in the platelet donor plasma and the content of platelets in the donor plasma in the range (100.0 -20.0) ×109/l, a linear relationship was revealed. When the content of platelets was more than 100.0×109/l, generated by platelet plasma, EPT increased, regardless of the increase in the content of platelets in the plasma under study. Conclusion: in case of thrombosis against the background of chemo-induced thrombocytopenia in the range (100.0 -20.0)×109/l, the patient should receive LMWH at a dose reduced in proportion to the content of platelets in the blood.

Proteomic profiling demonstrates inflammatory and endotheliopathy signatures associated with impaired cardiopulmonary exercise hemodynamic profile in Post Acute Sequelae of SARS-CoV-2 infection (PASC) syndrome.

Approximately 50% of patients who recover from the acute SARS-CoV-2 experience Post Acute Sequelae of SARS-CoV-2 infection (PASC) syndrome. The pathophysiological hallmark of PASC is characterized by impaired system oxygen extraction (EO2) on invasive cardiopulmonary exercise test (iCPET). However, the mechanistic insights into impaired EO2 remain unclear. We studied 21 consecutive iCPET in PASC patients with unexplained exertional intolerance. PASC patients were dichotomized into mildly reduced (EO2peak-mild) and severely reduced (EO2peak-severe) EO2 groups according to the median peak EO2 value. Proteomic profiling was performed on mixed venous blood plasma obtained at peak exercise during iCPET. PASC patients as a group exhibited depressed peak exercise aerobic capacity (peak VO2; 85 ± 18 vs. 131 ± 45% predicted; p = 0.0002) with normal systemic oxygen delivery, DO2 (37 ± 9 vs. 42 ± 15 mL/kg/min; p = 0.43) and reduced EO2 (0.4 ± 0.1 vs. 0.8 ± 0.1; p < 0.0001). PASC patients with EO2peak-mild exhibited greater DO2 compared to those with EO2peak-severe [42.9 (34.2-41.2) vs. 32.1 (26.8-38.0) mL/kg/min; p = 0.01]. The proteins with increased expression in the EO2peak-severe group were involved in inflammatory and fibrotic processes. In the EO2peak-mild group, proteins associated with oxidative phosphorylation and glycogen metabolism were elevated. In PASC patients with impaired EO2, there exist a spectrum of PASC phenotype related to differential aberrant protein expression and cardio-pulmonary physiologic response.PASC patients with EO2peak-severe exhibit a maladaptive physiologic and proteomic signature consistent with persistent inflammatory state and endothelial dysfunction, while in the EO2peak-mild group, there is enhanced expression of proteins involved in oxidative phosphorylation-mediated ATP synthesis along with an enhanced cardiopulmonary physiological response.

Validation and application of volumetric absorptive microsampling (VAMS) dried blood method for phenylalanine measurement in patients with phenylketonuria

BackgroundFrequent blood phenylalanine (Phe) measurement is required for phenylketonuria (PKU) patients for diagnosis and disease status monitoring. Though various methods are available for blood Phe measurement, there is a lack of validated quantitative methods for measuring Phe with less than 15% variability. A method to allow at home blood sample collection for the PKU community is in high demand. MethodsA volumetric absorptive microsampling (VAMS) dried blood collection high-performance liquid chromatography-tandem mass spectrometry (HPLC–MS/MS) method was developed and fully validated for blood Phe measurement in compliance with regulatory guidances. The method accuracy, precision, stability, selectivity, matrix and hematocrit effects were assessed. A venous plasma collection HPLC-MS/MS method was developed and validated as a reference method. 311 matching VAMS and plasma samples were collected from 24 PKU subjects in a Phase 2 clinical study. Phe measurements using the two methods were compared. ResultsBoth VAMS and the plasma sample collection methods met the acceptance criteria for Good Laboratory Practice (GLP) bioanalytical analysis. Comparisons showed a high Pearson’s correlation of 0.9813. The Passing-Bablok analysis showed that the difference was estimated to be less than 5% and Bland Altman analysis indicated that the difference was proportional with Phe concentration and for the majority of samples (88.85%) the measurement was within ±20% difference.Following 7 days treatment with 60 or 20 mg/kg/day PTC923 (Sepiapterin) or 20 mg/kg/day sapropterin, PKU patients exhibited respectively −206.4, −146.9, and −91.5 µmol/L reductions of blood Phe as measured by the VAMS method. ConclusionsConcordant results were obtained using VAMS and plasma methods, which demonstrated that VAMS is a reliable method for clinical applications to monitor blood Phe for PKU patients.

Case–control study of serum vitamin D concentrations in hospitalised patients with COVID-19 and hospitalised controls suffering with respiratory tract infections of differing aetiology

This study explored the prevalence of low serum vitamin D in patients admitted with acute respiratory tract infections (ARTIs) such as COVID-19. This study investigated whether patients with COVID-19 had...