Qualität und sichere Anästhesie für alle Kinder

Die Anaesthesiologie - Im Jahr 1989 haben die Vereinten Nationen die „United Nations Convention on the Rights of the Child“ (UNCRC) beschlossen und u. a. für Kinder der...     

A benchmark dose study of prenatal exposure to di(2-ethylhexyl) phthalate and behavioral problems in children

IntroductionPrenatal exposure to di(2-ethylhexyl) phthalate (DEHP) has been reported to be associated with adverse effects on neurodevelopment that yield behavior syndromes in young children with an estimated median exposure lower than the currently recommended tolerable daily intake (TDI) and reference dose (RfD).ObjectivesOur aim was to derive the benchmark dose for prenatal exposure to DEHP for the neurodevelopmental health in children.MethodsA total of 122 mother-child pairs from the Taiwan Maternal and Infant Cohort Study were analyzed for the dose-response relationship between maternal exposure to DEHP and children's behavioral syndromes evaluated at 8 years (n = 122, 2009), 11 years (n = 96, 2012), and 14 years (n = 78, 2015) of age. We employed a multivariate regression model to assess the statistical associations between the estimated maternal average daily intake of DEHP and child's individual CBCL scores for boys and girls at each separate age, followed by a mixed model for all the children across three ages accounting for individual variations. We then employed structural equation models by combining the children's specific behavioral problem scores at different ages and obtained a simulated overall latent score in relation to maternal exposure. Based on the established dose-response relationship, we derived the benchmark dose (BMD) and the lower limit (BMDL).ResultsAssociations of maternal DEHP exposure (median 4.54$\mu g/kg\_bw/day$) with the Child Behavior Checklist (CBCL) scores were all significant, except for somatic complaints, adjusting for child's age, gender, IQ, and family income. The BMDL, given a benchmark response of 0.10 (0.05) and a background response of 0.05, was 6.01 (2.16) $\mu g/kg\_bw/day$for an integrated CBCL score.ConclusionsThe current TDI (RfD) of 50 (20) $\mu g/kg\_bw/day$ for DEHP might not protect pregnant women for their children from behavioral problems. There remains the lack of comparable toxicological data. Further investigations are needed.     

Sacituzumab govitecan: breakthrough targeted therapy for triple-negative breast cancer

Introduction: Triple negative breast cancer (TNBC) is an aggressive breast cancer subtype associated with an increased risk of recurrence and cancer-related death. Unlike hormone receptor-positive or HER2-positive breast cancers, there are limited targeted therapies available to treat TNBC and cytotoxic chemotherapy remains the mainstay of treatment. Sacituzumab govitecan (IMMU-132) is an antibody-drug conjugate targeting Trop-2 expressing cells and selectively delivering SN-38, an active metabolite of irinotecan.

Areas covered: This review covers the mechanism of action, safety and efficacy of sacituzumab govitecan in patients with previously treated, metastatic TNBC. Additionally, efficacy data in other epithelial malignancies is included based on a PubMed search for ‘sacituzumab govitecan’ and ‘clinical trial’.

Expert opinion: Sacituzumab govitecan has promising anti-cancer activity in patients with metastatic TNBC previously treated with at least two prior lines of systemic therapy based on a single arm Phase I/II clinical trial. A confirmatory Phase III randomized clinical trial is ongoing. Sacituzumab govitecan has a manageable side effect profile, with the most common adverse events being nausea, neutropenia, and diarrhea. The activity of sacituzumab govitecan likely extends beyond TNBC with promising early efficacy data in many other epithelial cancers, including hormone receptor-positive breast cancer.     

Evaluation of a novel flow-controlled syringe infusion pump for precise and continuous drug delivery at low flow rates: a laboratory study

Syringe infusion pumps are used for the administration of short-acting drugs in anaesthesia and critical care medicine, but are prone to flow irregularities at low flow rates. A flow-controlled syringe infusion pump using an integrated flow sensor for feedback control represents a new approach to overcoming these limitations. This study compares the performance of a prototype flow-controlled syringe pump both at start-up, and during vertical displacement manoeuvres, with that of a standard infusion syringe pump. The novel pump almost completely eliminated delays at start-up and flow irregularities during hydrostatic pressure changes. Related fluctuations in plasma drug concentration were minimised and the known disadvantages of standard syringe infusion pumps currently used in clinical practice were reduced. Besides providing fast start-up to steady-state flow and precise continuous drug delivery at low flow rates during hydrostatic pressure changes, the new pump offers the potential for the development of target-controlled infusion algorithms for short-acting cardiovascular and other drugs.     

Simultaneous multi‐slice spin‐ and gradient‐echo dynamic susceptibility‐contrast perfusion‐weighted MRI of gliomas

Although combined spin‐ and gradient‐echo (SAGE) dynamic susceptibility‐contrast (DSC) MRI can provide perfusion quantification that is sensitive to both macrovessels and microvessels while correcting for T₁‐shortening effects, spatial coverage is often limited in order to maintain a high temporal resolution for DSC quantification. In this work, we combined a SAGE echo‐planar imaging (EPI) sequence with simultaneous multi‐slice (SMS) excitation and blipped controlled aliasing in parallel imaging (blipped CAIPI) at 3 T to achieve both high temporal resolution and whole brain coverage. Two protocols using this sequence with multi‐band (MB) acceleration factors of 2 and 3 were evaluated in 20 patients with treated gliomas to determine the optimal scan parameters for clinical use. ΔR₂*(t) and ΔR₂(t) curves were derived to calculate dynamic signal‐to‐noise ratio (dSNR), ΔR₂*‐ and ΔR₂‐based relative cerebral blood volume (rCBV), and mean vessel diameter (mVD) for each voxel. The resulting SAGE DSC images acquired using MB acceleration of 3 versus 2 appeared visually similar in terms of image distortion and contrast. The difference in the mean dSNR from normal‐appearing white matter (NAWM) and that in the mean dSNR between NAWM and normal‐appearing gray matter were not statistically significant between the two protocols. ΔR₂*‐ and ΔR₂‐rCBV maps and mVD maps provided unique contrast and spatial heterogeneity within tumors.     

Cannabinoid hyperemesis syndrome in two French emergency departments: a prospective cohort

Chronic cannabis use can be associated with uncontrollable vomiting and abdominal pain. Diagnostic criteria for cannabinoid hyperemesis syndrome (CHS) were defined in 2012 by Simonetto et al. The objectives of this study were to describe the prevalence of CHS, the patients' epidemiological characteristics, and to show the difficulties encountered in caring for these patients in emergency departments, the extent of health care and an unsuitable follow‐up in general practices. A prospective cohort of patients with CHS was recruited among a target population of patients leaving the adult emergency services of the Marseille hospitals Nord and La Timone between October 2017 and July 2018, with abdominal pain syndrome of unidentified etiology. Inclusion criteria for the CHS cohort were chronic cannabis use associated with nausea and vomiting. There were 48 patients included in the CHS cohort who took cannabis daily, in a target population of 2 848 patients (i.e. 1.6%). A hot shower was the most effective symptomatic treatment in 54.2% of cases. Patients suffering from CHS spent significantly more hours in emergency departments (11 vs. 6.5), and, on average, visits were more frequent (4.9 vs. 3). 20.3% of them were hospitalized to continue pain medication. Once out of hospital, follow‐up was limited, and weaning off cannabis, the only etiological treatment, was difficult to set up. Informing patients about CHS is essential, and a hot shower could be systematically proposed, thus limiting an unnecessary extent of health care. CHS is genuine, medical staff should be made aware of it in occupational training, and it should be seriously considered in health policies.     

Percutaneous thermal ablation of sacral metastases: Assessment of pain relief and local tumor control

PurposeTo retrospectively report on safety, pain relief and local tumor control achieved with percutaneous ablation of sacral bone metastases.Materials and methodsFrom February 2009 to June 2020, 23 consecutive patients (12 women and 11 men; mean age, 60 ± 8 [SD] years; median, 60; range: 48-80 years) with 23 sacral metastases underwent radiofrequency (RFA) or cryo-ablation (CA), with palliative or curative intent at our institution. Patients’ demographics and data pertaining to treated metastases, procedure-related variables, safety, and clinical evolution following ablation were collected and analyzed. Pain was assessed with numerical pain rating scale (NPRS).ResultsSixteen (70%) patients were treated with palliative and 7 (30%) with curative intent. Mean tumor diameter was 38 ± 19 (SD) mm (median, 36; range: 11-76). External radiation therapy had been performed on five metastases (5/23; 22%) prior to ablation. RFA was used in 9 (39%) metastases and CA in the remaining 14 (61%). Thermo-protective measures and adjuvant bone consolidation were used whilst treating 20 (87%) and 8 (35%) metastases, respectively. Five (22%) minor complications were recorded. At mean 31 ± 21 (SD) (median, 32; range: 2-70) months follow-up mean NPRS was 2 ± 2 (SD) (median, 1; range: 0–6) vs. 5 ± 1 (median, 5; range: 4–8; P < 0.001) at the baseline. Three metastases out of 7 (43%) undergoing curative ablation showed local progression at mean 4 ± 4 (SD) (median, 2; range: 1-8) months follow-up.ConclusionPercutaneous ablation of sacral metastases is safe and results in significant long-lasting pain relief. Local tumor control seems sub-optimal; however, further investigations are needed to confirm these findings due to paucity of data.