Nociception monitoring

This thesis concentrates on nociception monitoring during general anesthesia. Nociception is the process of encoding noxious stimuli, which are potential damaging events. During general anesthesia nociception will produce behavioral, autonomic and hormonal responses. We designed a series of studies to address the utility of nociception monitoring in clinical practice on hemodynamic stability, opioid consumption, arousal state and postoperative pain.LUMC / Geneeskund

Prediction of poor neurological outcome in comatose survivors of cardiac arrest: a systematic review.

To assess the ability of clinical examination, blood biomarkers, electrophysiology, or neuroimaging assessed within 7 days from return of spontaneous circulation (ROSC) to predict poor neurological outcome, defined as death, vegetative state, or severe disability (CPC 3-5) at hospital discharge/1 month or later, in comatose adult survivors from cardiac arrest (CA). PubMed, EMBASE, Web of Science, and the Cochrane Database of Systematic Reviews (January 2013-April 2020) were searched. Sensitivity and false-positive rate (FPR) for each predictor were calculated. Due to heterogeneities in recording times, predictor thresholds, and definition of some predictors, meta-analysis was not performed. Ninety-four studies (30,200 patients) were included. Bilaterally absent pupillary or corneal reflexes after day 4 from ROSC, high blood values of neuron-specific enolase from 24 h after ROSC, absent N20 waves of short-latency somatosensory-evoked potentials (SSEPs) or unequivocal seizures on electroencephalogram (EEG) from the day of ROSC, EEG background suppression or burst-suppression from 24 h after ROSC, diffuse cerebral oedema on brain CT from 2 h after ROSC, or reduced diffusion on brain MRI at 2-5 days after ROSC had 0% FPR for poor outcome in most studies. Risk of bias assessed using the QUIPS tool was high for all predictors. In comatose resuscitated patients, clinical, biochemical, neurophysiological, and radiological tests have a potential to predict poor neurological outcome with no false-positive predictions within the first week after CA. Guidelines should consider the methodological concerns and limited sensitivity for individual modalities. (PROSPERO CRD42019141169)

Does nociception monitor-guided anesthesia affect opioid consumption? a systematic review of randomized controlled trials

Monitors that estimate nociception during anesthesia may be used to guide opioid and other analgesics administration to optimize anesthesia care and possibly outcome. We reviewed the literature to evaluate current evidence of the effect of nociception-guided management over standard anesthesia practice during surgery. A systematic review of the literature on the effect of nociception monitoring on anesthesia practice was conducted. Reports were eligible if they compared nociception-guided anesthesia to standard practice during surgery. Primary endpoint of this review is intraoperative opioid consumption. Secondary endpoints included hemodynamic control, postoperative pain and pain treatment. We identified 12 randomized controlled trials that compared one of five different nociception monitoring techniques to standard anesthesia care. Most studies were single center studies of small sample size. Six studies reported intraoperative opioid consumption as primary outcome. There was considerable variability with respect to surgical procedure and anesthesia technique. For nociception monitors that were investigated by more than one study, analysis of the pooled data was performed. The surgical plethysmographic index was the only monitor for which an intra operative opioid sparing effect was found. For the other monitors, either no effect was detected, or pooled analysis could not be performed due to paucity of study data. On secondary outcomes, no consistent effect of nociception-guided anesthesia could be established. Although some nociception monitors show promising results, no definitive conclusions regarding the effect of nociception monitoring on intraoperative opioid consumption or other anesthesia related outcome can be drawn. Clinical trial numberPROSPERO ID 102913.Perioperative Medicine: Efficacy, Safety and Outcome (Anesthesiology/Intensive Care

A systematic review and meta-analysis of prognostic biomarkers in resectable esophageal adenocarcinomas

Targeted therapy is lagging behind in esophageal adenocarcinoma (EAC). To guide the development of new treatment strategies, we provide an overview of the prognostic biomarkers in resectable EAC treated with curative intent. The Medline, Cochrane and EMBASE databases were systematically searched, focusing on overall survival (OS). The quality of the studies was assessed using a scoring system ranging from 0–7 points based on modified REMARK criteria. To evaluate all identified prognostic biomarkers, the hallmarks of cancer were adapted to fit all biomarkers based on their biological function in EAC, resulting in the features angiogenesis, cell adhesion and extra-cellular matrix remodeling, cell cycle, immune, invasion and metastasis, proliferation, and self-renewal. Pooled hazard ratios (HR) and 95% confidence intervals (CI) were derived by random effects meta-analyses performed on each hallmarks of cancer feature. Of the 3298 unique articles identified, 84 were included, with a mean quality of 5.9 points (range 3.5–7). The hallmarks of cancer feature ‘immune’ was most significantly associated with worse OS (HR 1.88, (95%CI 1.20–2.93)). Of the 82 unique prognostic biomarkers identified, meta-analyses showed prominent biomarkers, including COX-2, PAK-1, p14ARF, PD-L1, MET, LC3B, IGFBP7 and LGR5, associated to each hallmark of cancer

Liquid crystalline oligo(p-phenylene vinylene)-terminated poly(propylene imine) dendrimers : synthesis and characterization

Different generations of poly(propylene imine) dendrimers modified peripherically with urea oligo(p-phenylene vinylene)s (OPV) having a 3,4,5-tri(dodecyloxy)phenyl mesogenic unit (OPV-dendrimers) were successfully synthesized and fully characterized. Although intramol. H-bonding exist between the urea linkages of the end groups, only weak interactions between the p-conjugated segments were obsd. in soln. The hydrogen-bonding interactions increased for higher generation dendrimers due to the closer proximity of the end groups, indicative of a more dense-shell packing. All generations of OPV-dendrimers showed liq. cryst. behavior in which the OPV-dendrimers have a homeotropic orientation. The temp. range of the liq. cryst. phase increased with higher generation. [on SciFinder (R)

Supramolecular dendritic pi-conjugated systems: synthesis of glycinylurea functionalized pi-conjugated diphenylanthracene guests and their complexation with dendritic hosts. Part I.

Glycinylurea functionalized p-conjugated diphenylanthracene guests (DPA guests) that bind to adamantyl urea modified dendritic hosts were synthesized and fully characterized by NMR spectroscopy (1H-NMR, 13C-NMR) and MALDI-TOF-MS. The resulting supramolecular assemblies have been investigated with respect to their binding properties. DPA guests molecules were able to click into urea functionalized N,N-bis methyl amine host as a result of acid-base (between COOH of the guest and amines of the host) and hydrogen bonding interactions (between the urea linkages of dendrimer and the guest). The guest molecules were bound as 1:1 inclusion complexes and the association constants for both guests have been calculated. Subsequently, an adamantyl urea modified fifth generation poly(propylene imine) dendrimer was synthesized as a multivalent host which contains 32 N,Nbis amine binding sites. Size exclusion chromatography showed that 32 of the DPA guests strongly bind to the fifth generation adamantyl functionalized dendritic host

Supramolecular dendritic pi-conjugated systems: synthesis of glycinylurea functionalized pi-conjugated diphenylanthracene guests and their complexation with dendritic hosts. Part I.

Glycinylurea functionalized p-conjugated diphenylanthracene guests (DPA guests) that bind to adamantyl urea modified dendritic hosts were synthesized and fully characterized by NMR spectroscopy (1H-NMR, 13C-NMR) and MALDI-TOF-MS. The resulting supramolecular assemblies have been investigated with respect to their binding properties. DPA guests molecules were able to click into urea functionalized N,N-bis methyl amine host as a result of acid-base (between COOH of the guest and amines of the host) and hydrogen bonding interactions (between the urea linkages of dendrimer and the guest). The guest molecules were bound as 1:1 inclusion complexes and the association constants for both guests have been calculated. Subsequently, an adamantyl urea modified fifth generation poly(propylene imine) dendrimer was synthesized as a multivalent host which contains 32 N,Nbis amine binding sites. Size exclusion chromatography showed that 32 of the DPA guests strongly bind to the fifth generation adamantyl functionalized dendritic host

Supramolecular dendritic pi-conjugated systems: synthesis of glycinylurea functionalized pi-conjugated diphenylanthracene guests and their complexation with dendritic hosts. Part I.

Glycinylurea functionalized p-conjugated diphenylanthracene guests (DPA guests) that bind to adamantyl urea modified dendritic hosts were synthesized and fully characterized by NMR spectroscopy (1H-NMR, 13C-NMR) and MALDI-TOF-MS. The resulting supramolecular assemblies have been investigated with respect to their binding properties. DPA guests molecules were able to click into urea functionalized N,N-bis methyl amine host as a result of acid-base (between COOH of the guest and amines of the host) and hydrogen bonding interactions (between the urea linkages of dendrimer and the guest). The guest molecules were bound as 1:1 inclusion complexes and the association constants for both guests have been calculated. Subsequently, an adamantyl urea modified fifth generation poly(propylene imine) dendrimer was synthesized as a multivalent host which contains 32 N,Nbis amine binding sites. Size exclusion chromatography showed that 32 of the DPA guests strongly bind to the fifth generation adamantyl functionalized dendritic host

Supramolecular dendritic pi-conjugated systems, II. Synthesis of glycinylurea functionalized pi-conjugated diphenylanthracene guests and their complexation with dendritic hosts

A new guest based on diphenylanthracene functionalized with glycinylurea was synthesized. The guest having trisdodecyloxyalkylic groups has been fully characterized by NMR spectroscopy (1H-NMR, 13C-NMR) and MALDI-TOF-MS. The resulting Guest was complexed with dendritic adamantyl urea Host of fifth generation and the association constant has been calculated. By size exclusion chromatography was proved that the multivalent host strongly binds 32 molecules of the DPA guests as a result of acid-base and hydrogen bonding interactions