Minimally invasive quantification of cerebral P2X7R occupancy using dynamic [18F]JNJ-64413739 PET and MRA-driven image derived input function

Abstract[18F]JNJ-64413739 has been evaluated as PET-ligand for in vivo quantification of purinergic receptor subtype 7 receptor (P2X7R) using Logan graphical analysis with a metabolite-corrected arterial plasma input function. In the context of a P2X7R PET dose occupancy study, we evaluated a minimally invasive approach by limiting arterial sampling to baseline conditions. Meanwhile, post dose distribution volumes (VT) under blocking conditions were estimated by combining baseline blood to plasma ratios and metabolite fractions with an MR angiography driven image derived input function (IDIF). Regional postdose VT,IDIF values were compared with corresponding VT,AIF estimates using a arterial input function (AIF), in terms of absolute values, test–retest reliability and receptor occupancy. Compared to an invasive AIF approach, postdose VT,IDIF values and corresponding receptor occupancies showed only limited bias (Bland–Altman analysis: 0.06 ± 0.27 and 3.1% ± 6.4%) while demonstrating a high correlation (Spearman ρ = 0.78 and ρ = 0.98 respectively). In terms of test–retest reliability, regional intraclass correlation coefficients were 0.98 ± 0.02 for VT,IDIF compared to 0.97 ± 0.01 for VT,AIF. These results confirmed that a postdose IDIF, guided by MR angiography and using baseline blood and metabolite data, can be considered for accurate [18F]JNJ-64413739 PET quantification in a repeated PET study design, thus avoiding multiple invasive arterial sampling and increasing dosing flexibility.

Evaluation of Mathematical Arterialization of Venous Blood in Intensive Care and Pulmonary Ward Patients

<b><i>Background:</i></b> Arterial blood gases are important when assessing acute or critically ill patients. Capillary blood and mathematical arterialization of venous blood have been proposed as alternative methods, eliminating pain and complications of arterial puncture. <b><i>Objectives:</i></b> This study compares the arterial samples, arterialized venous samples, and capillary samples in ICU and pulmonary ward patients. <b><i>Method:</i></b> Ninety-one adult patients with respiratory failure were included in the analysis. Arterial, peripheral venous, and mathematically arterialized venous samples were compared in all patients using Bland-Altman analysis, with capillary samples included in 36 patients. <b><i>Results:</i></b> Overall for pH and PCO₂, arterialized venous values, and in the subset of 36 patients, capillary values, compared well to arterial values and were within the pre-defined clinically acceptable differences (pH ± 0.05 and PCO₂ ± 0.88 kPa). For PO₂, arterialized or capillary values describe arterial with similar precision (PO₂ arterialized −0.03, LoA −1.48 to 1.42 kPa and PO₂ capillary 0.82, LoA −1.36 to 3 kPa), with capillary values underestimating arterial. <b><i>Conclusions:</i></b> Mathematical arterialization functions well in a range of patients in an ICU and ward outside the country of development of the method. Furthermore, accuracy and precision are similar to capillary blood samples. When considering a replacement for arterial sampling in ward patients, using capillary sampling or mathematical arterialization should depend on logistic ease of implementation and use rather than improved measurements of using either technique.

Non-invasive Standardised Uptake Value for Verification of the Use of Previously Validated Reference Region for [18F]Flortaucipir and [18F]Florbetapir Brain PET Studies

Purpose The simplified reference tissue model (SRTM) is commonly applied for the quantification of brain positron emission tomography (PET) studies, particularly because it avoids arterial cannulation. SRTM requires a validated reference region which is obtained by baseline-blocking or displacement studies. Once a reference region is validated, the use should be verified for each new subject. This verification normally requires volume of distribution (VT) of a reference region. However, performing dynamic scanning and arterial sampling is not always possible, specifically in elderly subjects and in advanced disease stages. The aim of this study was to investigate the use of non-invasive standardised uptake value (SUV) approaches, in comparison to VT, as a verification of the previously validated grey matter cerebellum reference region for [18F]flortaucipir and [18F]florbetapir PET imaging in Alzheimer’s disease (AD) patients and controls. Procedures Dynamic 130-min [18F]flortaucipir PET scans obtained from nineteen subjects (10 AD patients) and 90-min [18F]florbetapir dynamic scans obtained from fourteen subjects (8 AD patients) were included. Regional VT’s were estimated for both tracers and were considered the standard verification of the previously validated reference region. Non-invasive SUVs corrected for body weight (SUVBW), lean body mass (SUL), and body surface area (SUVBSA) were obtained by using later time intervals of the dynamic scans. Simulations were also performed to assess the effect of flow and specific binding (BPND) on the SUVs. Results A low SUV corresponded well with a low VT for both [18F]flortaucipir and [18F]florbetapir. Simulation confirmed that SUVs were only slightly affected by flow changes and that increases in SUV were predominantly determined by the presence of specific binding. Conclusions In situations where dynamic scanning and arterial sampling is not possible, a low SUV(80–100 min) for [18F]flortaucipir and a low SUV(50–70 min) for [18F]florbetapir may be used as indication for absence of specific binding in the grey matter cerebellum reference region.

The glucose error in arterial sampling: assessing staff awareness and the effect of sampling technique*

Background Using a dextrose-containing solution, instead of normal saline, to maintain the patency of an arterial cannula results in the admixture of glucose in line samples. This can misguide the clinician down an inappropriate treatment pathway for hyperglycaemia. Methods Following a near-miss and subsequent educational and training efforts at our institution, we conducted two simulations: (1) to observe whether 20 staff would identify a 5% dextrose/0.9% saline flush solution as the cause for a patient’s refractory hyperglycaemia, and (2) to compare different arterial line sampling techniques for glucose contamination. Results (1) Only 2/20 participants identified the incorrect dextrose-containing flush solution, with the remainder choosing to escalate insulin therapy to levels likely to risk fatality, and (2) glucose contamination occurred regardless of sampling technique. Conclusion Despite national guidance and local educational efforts, this is still an under-recognised error. Operator-focussed preventative strategies have not been effective and an engineered solution is needed.

Monitoring Anticoagulation with Unfractionated Heparin on Renal Replacement Therapy. Which Is the Best aPTT Sampling Site?

BackgroundControlled anticoagulation is key to maintaining continuous blood filtration therapies. Objective: The study aimed to compare different blood sampling sites for activated partial thromboplastin time (aPTT) to evaluate anticoagulation with unfractionated heparin (UFH) in continuous renal replacement therapy (CRRT) and identify the most appropriate sampling site for safe patient anticoagulation and increased filter life span.MethodThe study was a prospective observational single-centre investigation targeting intensive care unit (ICU) patients on CRRT using an anticoagulation protocol based on patient characteristics and a weight-based modified nomogram. Eighty-four patients were included in the study. Four sampling sites were assessed: heparin free central venous nondialysis catheter (CVC), an arterial line with heparinised flush (Artery), a circuit access line (Access), and a circuit return line (Postfilter). Blood was sampled from each of four different sites on every patient, four hours after the first heparin bolus. aPTT was determined using a rapid clot detector, point of care device.ResultsA high positive correlation was obtained for aPTT values between CVC and Access sampling sites (r (84) =0.72; p <0 .05) and a low positive correlation between CVC and Arterial sampling site (r (84) =0.46, p < 0.05). When correlated by artery age, the young Artery (1-3 day old) correlates with CVC, Access and Postfilter (r (45) = 0.74, p >0.05). The aPTT values were significantly higher at Postfilter and Arterial sampling site, older than three days, compared to the CVC sampling site (p<0.05).ConclusionConsidering patient bleeding risks and filter life span, the optimal sampling sites for safe assessment of unfractionated heparin anticoagulation on CRRT during CVVHDF were the central venous catheter using heparin free lavage saline solution, a heparinised flushed arterial catheter not older than three days, and a circuit access line.

Reducing pain by using venous blood gas instead of arterial blood gas (VEINART): a multicentre randomised controlled trial

IntroductionVenous sampling for blood gas analysis has been suggested as an alternative to arterial sampling in order to reduce pain. The main objective was to compare pain induced by venous and arterial sampling and to assess whether the type of sampling would affect clinical management or not.MethodsWe performed an open-label randomised multicentre prospective study in four French EDs during a 4-week period. Non-hypoxaemic adults, whose medical management required blood gas analysis, were randomly allocated using a computer-generated randomisation list stratified by centres with an allocation ratio of 1:1 using random blocks to one of the two arms: venous or arterial sampling. The primary outcome was the maximal pain during sampling, using the visual analogue scale. Secondary outcomes pertained to ease of sampling as rated by the nurse drawing the blood, and physician satisfaction regarding usefulness of biochemical data.Results113 patients were included: 55 in the arterial and 58 in the venous sampling group. The mean maximal pain was 40.5 mm±24.9 mm and 22.6 mm±20.2 mm in the arterial group and the venous group, respectively, accounting for a mean difference of 17.9 mm (95% CI 9.6 to 26.3) (p<0.0001). Ease of blood sampling was greater in the venous group as compared with the arterial group (p=0.02). The usefulness of the results, evaluated by the prescriber, did not significantly differ (p=0.25).ConclusionsVenous blood gas is less painful for patients than ABG in non-hypoxaemic patients. Venous blood gas should replace ABG in this setting.Trial registration numberNCT03784664.

The utility of peripheral venous lactate in emergency department patients with normal and higher lactate levels: A prospective observational study

Objective: to assess the utility of peripheral venous lactate (PVL) in Emergency Department patients. Methods: arteriovenous agreement was assessed in three subgroups: PVL <2 mmol/l, PVL ≥ 2 mmol/l to < 4 mmol/l and PVL ≥ 4 mmol/l. The predictive value of PVL to predict arterial lactate (AL) ≥2 mmol/l was assessed at different cut-off values. Results: 74 samples were analysed. The venous-arterial mean difference and 95% limits of agreement for the subgroups were 0.25 mmol/l (-0.18 to 0.68), 0.37 mmol/l (-0.57 to 1.32) and -0.89 mmol/l (-3.75 to 1.97). PVL ≥2 mmol/l predicts AL ≥2 mmol/l with 100% sensitivity. Conclusion: PVL <2 mmol/l rules out arterial hyperlactatemia. As agreement declines in higher levels, arterial sampling should be considered.