Glomerular filtration rate in critically ill neonates and children: creatinine-based estimations versus iohexol-based measurements.

BACKGROUND: Acute kidney injury (AKI) and augmented renal clearance (ARC), both alterations of the glomerular filtration rate (GFR), are prevalent in critically ill children and neonates. AKI and ARC prevalence estimates are based on estimation of GFR (eGFR) using serum creatinine (SCr), which is known to be inaccurate. We aimed to test our hypothesis that AKI prevalence will be higher and ARC prevalence will be lower in critically ill children when using iohexol-based measured GFR (mGFR), rather than using eGFR. Additionally, we aimed to investigate the performance of different SCr-based eGFR methods. METHODS: In this single-center prospective study, critically ill term-born neonates and children were included. mGFR was calculated using a plasma disappearance curve after parenteral administration of iohexol. AKI diagnosis was based on the KDIGO criteria, SCr-based eGFR, and creatinine clearance (CrCL). Differences between eGFR and mGFR were determined using Wilcoxon signed-rank tests and by calculating bias and accuracy (percentage of eGFR values within 30% of mGFR values). RESULTS: One hundred five children, including 43 neonates, were included. AKI prevalence was higher based on mGFR (48%), than with KDIGO or eGFR (11-40%). ARC prevalence was lower with mGFR (24%) compared to eGFR (38-51%). eGFR equations significantly overestimated mGFR (60-71 versus 41 ml/min/1.73 m2, p < 0.001-0.002). Accuracy was highest with eGFR equations based on age- and sex-dependent equations (up to 59%). CONCLUSION: Iohexol-based AKI prevalence was higher and ARC prevalence lower compared to standard SCr-based eGFR methods. Age- and sex-dependent equations for eGFR (eGFR-Smeets for neonates and eGFR-Pierce for children) best approached measured GFR and should preferably be used to optimize diagnosis of AKI and ARC in this population. A higher resolution version of the Graphical abstract is available as Supplementary information.

The Impact of Baseline PSMA PET/CT Versus CT on Outcomes of 223Ra Therapy in Metastatic Castration-Resistant Prostate Cancer Patients.

Imaging before 223Ra-dichloride (223Ra) therapy is crucial for selecting metastatic castration-resistant prostate cancer (mCRPC) patients with bone-only disease. The purpose of this study was to evaluate if baseline prostate-specific membrane antigen (PSMA) PET/CT (bPSMA) versus CT is associated with outcomes of 223Ra therapy. Methods: A secondary analysis of the data of a prospective observational study (NCT04995614) was performed. Patients received a maximum of 6 223Ra cycles and were retrospectively divided into the bPSMA or baseline CT (bCT) groups. All patients received baseline bone scintigraphy. Primary endpoints were alkaline phosphatase and prostate-specific antigen response. Secondary endpoints were overall survival (OS) and radiologic response. Results: Between 2017 and 2020, 122 mCRPC patients were included: 18 (14.8%) in the bPSMA group and 104 (85.2%) in the bCT group. All baseline characteristics were comparable. No significant differences in alkaline phosphatase or prostate-specific antigen response were found. The bCT group showed an OS significantly shorter than that of the bPSMA group (12.4 vs. 19.9 mo, P = 0.038). In 31 of 76 patients (40.1%) in the bCT group who also received posttherapy CT, lymph node or visceral metastases (soft-tissue involvement [STI]) were detected after 223Ra therapy, compared with 0 of 15 patients in the bPSMA group who received posttherapy PSMA PET/CT or CT. No significant difference in OS was found between patients in the bCT or posttherapy CT subgroup without STI (46/76) and the bPSMA group. Conclusion: bPSMA versus CT does not seem to impact biochemical response during 223Ra therapy in mCRPC patients. Nevertheless, patients in the bCT group had a significantly shorter OS, most likely due to underdetection of STI in this group. Therefore, replacing bCT with PSMA PET/CT appears to be a valuable screening method for identifying patients who will benefit most from 223Ra therapy.

Public acceptance and uptake of oesophageal adenocarcinoma screening strategies: A mixed-methods systematic review.

Oesophageal adenocarcinoma (OAC) is increasingly diagnosed and often fatal, thus representing a growing global health concern. Screening for its precursor, Barrett's oesophagus (BO), combined with endoscopic surveillance and treatment of dysplasia might prevent OAC. This review aimed to systematically explore the public's acceptance and uptake of novel screening strategies for OAC. We systematically searched three electronic databases (Ovid Medline/PubMed, Ovid EMBASE and PsycINFO) from date of inception to July 2, 2021 and hand-searched references to identify original studies published in English on acceptability and uptake of OAC screening. Two reviewers independently reviewed and appraised retrieved records and two reviewers extracted data (verified by one other reviewer). Of the 3674 unique records, 19 studies with 15 249 participants were included in the review. Thematic analysis of findings showed that acceptability of OAC screening is related to disease awareness, fear, belief in benefit, practicalities and physical discomfort. The findings were mapped on the Integrated Screening Action Model. Minimally invasive screening tests are generally well-tolerated: patient-reported outcomes were reported for sedated upper endoscopy (tolerability ++), transnasal endoscopy (tolerability +), tethered capsule endomicroscopy (tolerability +/-), and the Cytosponge-TFF3 test (acceptability ++). In discrete choice experiments, individuals mainly valued screening test accuracy. OAC screening has been performed in trials using conventional upper endoscopy (n = 231 individuals), transnasal endoscopy (n = 966), capsule endoscopy (n = 657) and the Cytosponge-TFF3 test (n = 9679), with uptake ranging from 14·5% to 48·1%. Intended participation in OAC screening in questionnaire-based studies ranged from 62·8% to 71·4%. We conclude that the general public seems to have interest in OAC screening. The findings will provide input for the design of a screening strategy that incorporates the public's values and preferences to improve informed participation. Identification of a screening strategy effective in reducing OAC mortality and morbidity remains a crucial prerequisite. Funding: This study was funded by the Netherlands Organization for Health Research and Development (ZonMw) under grant 555,004,206.

Ventilator-associated pneumonia rates after introducing selective digestive tract decontamination.

The incidence of ventilator-associated pneumonia (VAP) before and after the introduction of selective oral decontamination (SOD) only and selective digestive tract decontamination (SDD) in a general intensive care population was examined. SOD as standard of care was introduced in December 2010 and SDD, including SOD, in January 2012 for all patients with an expected length of intensive care unit (ICU) stay of at least 48 h. The diagnosis of VAP was based on clinical criteria and quantitative cultures of bronchoalveolar lavage fluid. A total of 4945 mechanically ventilated patients accounting for 37 554 ventilator days in the period from 2005 to 2013 were analyzed. The incidence of VAP per 1000 ventilator days declined significantly from 4.38 ± 1.64 before to 1.64 ± 0.43 after introduction of SOD/SDD (p = 0.007). Implementation of SOD/SDD as standard of care in ICUs may thus be effective in preventing VAP.