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This study investigates the incidence of extrahepatic perfusion and incomplete hepatic perfusion at intraoperative methylene blue testing and on postoperative nuclear imaging in patients undergoing hepatic arterial infusion pump (HAIP) chemotherapy. The first 150 consecutive patients who underwent pump implantation in the Netherlands were included. All patients underwent surgical pump implantation with the catheter in the gastroduodenal artery. All patients underwent intraoperative methylene blue testing and postoperative nuclear imaging (99mTc-Macroaggregated albumin SPECT/CT) to determine perfusion via the pump. Patients were included between January-2018 and December-2021 across eight centers. During methylene blue testing, 29.3% had extrahepatic perfusion, all successfully managed intraoperatively. On nuclear imaging, no clinically relevant extrahepatic perfusion was detected (0%, 95%CI: 0.0–2.5%). During methylene blue testing, 2.0% had unresolved incomplete hepatic perfusion. On postoperative nuclear imaging, 8.1% had incomplete hepatic perfusion, leading to embolization in only 1.3%. Methylene blue testing during pump placement for intra-arterial chemotherapy identified extrahepatic perfusion in 29.3% of patients, but could be resolved intraoperatively in all patients. Postoperative nuclear imaging found no clinically relevant extrahepatic perfusion and led to embolization in only 1.3% of patients. The role of routine nuclear imaging after HAIP implantation should be studied in a larger cohort. [ABSTRACT FROM AUTHOR]

Dementia is a clinical diagnosis without curative treatment. It is uncertain whether ancillary testing is beneficial for patients. This study investigates the association between use of diagnostic tests and time to poor outcome and health care costs. Nationwide register-based cohort study using health care reimbursement data in the Netherlands. All Dutch hospitals, including 13,312 patients diagnosed with dementia in 2018. Diagnostic testing included computed tomography or magnetic resonance imaging (CT/MRI), neuropsychological examination (NPE), nuclear imaging (PET/SPECT), electroencephalography (EEG), and cerebrospinal fluid (CSF) testing. We compared time to poor outcome (institutionalization or death) and costs per month from 2018 to 2021 between those who underwent a specific diagnostic test in previous years to controls, propensity score matched for age, sex, type of hospital, and comorbidity. Time to poor outcome in those who underwent CT/MRI, EEG, or CSF testing was similar to those who did not, but was longer for those who underwent NPE. Time to poor outcome was shorter in patients who underwent PET/SPECT. Patients who underwent CSF testing or PET/SPECT had higher mean total health care costs as compared to controls (CSF €248, 95% CI 64-433; PET/SPECT: €315, 95% CI 179-451). NPE during the diagnostic trajectory was associated with lower total health care cost (–€127, 95% CI –62, –193). NPE was associated with longer time to poor outcome and lower health care costs, potentially due to confounding by indication. Patients who underwent neuroimaging (CT, MRI, SPECT/PET), CSF testing, or EEG for dementia diagnostics did not experience a longer time to poor outcome or lower health care costs. This emphasizes the importance of clinical examination as anchor for the diagnosis of dementia. [ABSTRACT FROM AUTHOR]

Background: In order to acquire accurate drug pharmacokinetic information, which is required for tissue dosimetry, micro-SPECT must be quantitative to allow for an accurate assessment of radioligand activity in the relevant tissue. This study investigates the feasibility of deriving accurate mouse-specific time-integrated drug pharmacokinetic data in mouse kidneys from activity measurements using micro-SPECT. Methods: An animal experiment was carried out to evaluate the accuracy of 131I activity quantification in mouse kidneys (mean tissue volume of 0.140 mL) using a micro-SPECT system against conventional ex vivo gamma counting (GC) in a NaI(Tl) detector. The imaging setting investigated was that of the mouse biodistribution of a 131I-labelled single-domain antibody fragment (sdAb), currently being investigated for targeted radionuclide therapy of HER2-expressing cancer. SPECT imaging of 131I 365-keV photons was done with a VECTor/CT system (MILabs, Netherlands) using a high-energy mouse collimator with 1.6-mm-diameter pinholes. For both activity quantification techniques, the pharmacokinetic profile of the radioligand from approximately 1–73 h p.i. was derived and the time-integrated activity coefficient per gram of tissue (ã/M) was estimated. Additionally, SPECT activity recovery coefficients were determined in a phantom setting. Results: SPECT activities underestimate the reference activities by an amount that is dependent on the 131I activity concentration in the kidney, and thus on the time point of the pharmacokinetic profile. This underestimation is around − 12% at 1.5 h (2.89 MBq mL−1 mean reference activity concentration), − 13% at 6.6 h (149 kBq mL−1), − 40% at 24 h (17.6 kBq mL−1) and − 46% at 73 h (5.2 kBq mL−1) p.i. The ã/M value estimated from SPECT activities is, nevertheless, within − 14% from the reference (GC) ã/M value. Furthermore, better quantitative accuracy (within 2% from GC) in the SPECT ã/M value is achieved when SPECT activities are compensated for partial recovery with a phantom-based recovery coefficient of 0.85. Conclusion: The SPECT imaging system used, together with a robust activity quantification methodology, allows an accurate estimation of time-integrated pharmacokinetic information of the 131I-labelled sdAb in mouse kidneys. This opens the possibility to perform mouse-specific kidney-tissue dosimetry based on pharmacokinetic data acquired in vivo on the same mice used in nephrotoxicity studies. [ABSTRACT FROM AUTHOR]

Background: It is uncertain whether a diagnostic strategy supplemented by early coronary computed tomography angiography (CCTA) is superior to contemporary standard optimal care (SOC) encompassing high-sensitivity troponin assays (hs-troponins) for patients suspected of acute coronary syndrome (ACS) in the emergency department (ED).Objectives: This study assessed whether a diagnostic strategy supplemented by early CCTA improves clinical effectiveness compared with contemporary SOC.Methods: In a prospective, open-label, multicenter, randomized trial, we enrolled patients presenting with symptoms suggestive of an ACS at the ED of 5 community and 2 university hospitals in the Netherlands. Exclusion criteria included the need for urgent cardiac catheterization and history of ACS or coronary revascularization. The primary endpoint was the number of patients identified with significant coronary artery disease requiring revascularization within 30 days.Results: The study population consisted of 500 patients, of whom 236 (47%) were women (mean age 54 ± 10 years). There was no difference in the primary endpoint (22 [9%] patients underwent coronary revascularization within 30 days in the CCTA group and 17 [7%] in the SOC group [p = 0.40]). Discharge from the ED was not more frequent after CCTA (65% vs. 59%, p = 0.16), and length of stay was similar (6.3 h in both groups; p = 0.80). The CCTA group had lower direct medical costs (€337 vs. €511, p < 0.01) and less outpatient testing after the index ED visit (10 [4%] vs. 26 [10%], p < 0.01). There was no difference in incidence of undetected ACS.Conclusions: CCTA, applied early in the work-up of suspected ACS, is safe and associated with less outpatient testing and lower costs. However, in the era of hs-troponins, CCTA does not identify more patients with significant CAD requiring coronary revascularization, shorten hospital stay, or allow for more direct discharge from the ED. (Better Evaluation of Acute Chest Pain with Computed Tomography Angiography [BEACON]; NCT01413282). [ABSTRACT FROM AUTHOR]

Background.Minor stresses measured in daily life have repeatedly been associated with increased momentary psychotic experiences, both in individuals with psychotic disorders and in persons who are genetically at an increased risk for these disorders. Severe hearing impairment (SHI) is an environmental risk factor for psychotic disorder, possibly due to the experience of social exclusion. The aim of the current study is to investigate whether people with SHI exhibit higher levels of psychotic reactivity to social stressors in daily life than normal-hearing controls and whether this reactivity is associated with decreased baseline dopamine (DA) D2/3 receptor availability and/or elevated DA release following a dexamphetamine challenge.Method.We conducted an experience sampling study in 15 young adults with SHI and 19 matched normal-hearing controls who had previously participated in a single photon emission computed tomography study measuring DA D2/3 receptor availability and DA release in response to dexamphetamine.Results.The association between social stress and momentary psychotic experiences in daily life was stronger among SHI participants than among normal-hearing controls. Interactions between social stress and baseline striatal DA D2/3 receptor availability or DA release were not significant in multilevel models of momentary psychotic experiences including age, sex and tobacco use.Conclusions.While both elevated striatal DA release and elevated psychotic stress reactivity have been found in the same population defined by an environmental risk factor, SHI, their inter-relationship cannot be established. Further research is warranted to clarify the association between biological and psychological endophenotypes and psychosis risk. [ABSTRACT FROM AUTHOR]