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- Pauwels, A, et al.
(författare)
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How to select patients for antireflux surgery? The ICARUS guidelines (international consensus regarding preoperative examinations and clinical characteristics assessment to select adult patients for antireflux surgery)
- 2019
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Ingår i: Gut. - : BMJ. - 1468-3288 .- 0017-5749. ; 68:11, s. 1928-1941
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Tidskriftsartikel (refereegranskat)abstract
- Antireflux surgery can be proposed in patients with GORD, especially when proton pump inhibitor (PPI) use leads to incomplete symptom improvement. However, to date, international consensus guidelines on the clinical criteria and additional technical examinations used in patient selection for antireflux surgery are lacking. We aimed at generating key recommendations in the selection of patients for antireflux surgery.DesignWe included 35 international experts (gastroenterologists, surgeons and physiologists) in a Delphi process and developed 37 statements that were revised by the Consensus Group, to start the Delphi process. Three voting rounds followed where each statement was presented with the evidence summary. The panel indicated the degree of agreement for the statement. When 80% of the Consensus Group agreed (A+/A) with a statement, this was defined as consensus. All votes were mutually anonymous.ResultsPatients with heartburn with a satisfactory response to PPIs, patients with a hiatal hernia (HH), patients with oesophagitis Los Angeles (LA) grade B or higher and patients with Barrett’s oesophagus are good candidates for antireflux surgery. An endoscopy prior to antireflux surgery is mandatory and a barium swallow should be performed in patients with suspicion of a HH or short oesophagus. Oesophageal manometry is mandatory to rule out major motility disorders. Finally, oesophageal pH (±impedance) monitoring of PPI is mandatory to select patients for antireflux surgery, if endoscopy is negative for unequivocal reflux oesophagitis.ConclusionWith the ICARUS guidelines, we generated key recommendations for selection of patients for antireflux surgery.
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- Bountra, K., et al.
(författare)
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Structural basis for antibacterial peptide self-immunity by the bacterial ABC transporter McjD
- 2017
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Ingår i: Embo Journal. - : EMBO. - 0261-4189 .- 1460-2075. ; 36:20, s. 3062-3079
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Tidskriftsartikel (refereegranskat)abstract
- Certain pathogenic bacteria produce and release toxic peptides to ensure either nutrient availability or evasion from the immune system. These peptides are also toxic to the producing bacteria that utilize dedicated ABC transporters to provide self-immunity. The ABC transporter McjD exports the antibacterial peptide MccJ25 in Escherichia coli. Our previously determined McjD structure provided some mechanistic insights into antibacterial peptide efflux. In this study, we have determined its structure in a novel conformation, apo inward-occluded and a new nucleotide-bound state, high-energy outward-occluded intermediate state, with a defined ligand binding cavity. Predictive cysteine cross-linking in E.coli membranes and PELDOR measurements along the transport cycle indicate that McjD does not undergo major conformational changes as previously proposed for multi-drug ABC exporters. Combined with transport assays and molecular dynamics simulations, we propose a novel mechanism for toxic peptide ABC exporters that only requires the transient opening of the cavity for release of the peptide. We propose that shielding of the cavity ensures that the transporter is available to export the newly synthesized peptides, preventing toxic-level build-up.
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- Cock, C., et al.
(författare)
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Effects of remifentanil on esophageal and esophagogastric junction (EGJ) bolus transit in healthy volunteers using novel pressure-flow analysis
- 2018
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Ingår i: Neurogastroenterology and Motility. - : John Wiley & Sons. - 1350-1925 .- 1365-2982. ; 30:2
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Remifentanil is associated with subjective dysphagia and an objective increase in aspiration risk. Studies of opioid effects have shown decreased lower esophageal sphincter relaxation. We assessed bolus transit through the esophagus and esophagogastric junction (EGJ) during remifentanil administration using objective pressure-flow analysis.METHODS: Data from 11 healthy young participants (23±3 years, 7 M) were assessed for bolus flow through the esophagus and EGJ using high-resolution impedance manometry (Manoscan™, Sierra Scientific Instruments, Inc., LES Angeles, CA, USA) with 36 pressure and 18 impedance segments. Data were analyzed for esophageal pressure topography and pressure-flow analysis using custom Matlab analyses (Mathworks, Natick, USA). Paired t tests were performed with a P-value of < .05 regarded as significant.KEY RESULTS: Duration of bolus flow through (remifentanil/R 3.0±0.3 vs baseline/B 5.0 ± 0.4 seconds; P < .001) and presence at the EGJ (R 5.1 ± 0.5 vs B 7.1 ± 0.5 seconds; P = .001) both decreased during remifentanil administration. Distal latency (R 5.2 ± 0.4 vs B 7.5 ± 0.2 seconds; P < .001) and distal esophageal distension-contraction latency (R 3.5 ± 0.1 vs B 4.7 ± 0.2 seconds; P < .001) were both reduced. Intrabolus pressures were increased in both the proximal (R 5.3 ± 0.9 vs B 2.6 ± 1.3 mm Hg; P = .01) and distal esophagus (R 8.6 ± 1.7 vs B 3.1 ± 0.8 mm Hg; P = .001). There was no evidence of increased esophageal bolus residue.CONCLUSIONS AND INFERENCES: Remifentanil-induced effects were different for proximal and distal esophagus, with a reduced time for trans-sphincteric bolus flow at the EGJ, suggestive of central and peripheral μ-opioid agonism. There were no functional consequences in healthy subjects.
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- Doeltgen, Sebastian H., et al.
(författare)
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Remifentanil alters sensory neuromodulation of swallowing in healthy volunteers : Quantification by a novel pressure-impedance analysis
- 2016
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Ingår i: American Journal of Physiology - Gastrointestinal and Liver Physiology. - Bethesda, USA : American Physiological Society. - 0193-1857 .- 1522-1547. ; 310:11, s. G1176-G1182
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Tidskriftsartikel (refereegranskat)abstract
- Exposure to remifentanil contributes to an increased risk of pulmonary aspiration, likely through reduced pharyngeal contractile vigour and diminished bolus propulsion during swallowing. Here, we employed a novel high resolution pressure-flow analysis to quantify the biomechanical changes across the upper esophageal sphincter (UES). Eleven healthy young participants (mean age 23.3±3.1 years, 7 male) received remifentanil via intravenous target controlled infusion with an effect-site concentration of 3 ng/ml. Before and 30 min following commencement of remifentanil administration, participants performed ten 10 ml saline swallows while pharyngo-esophageal manometry and electrical impedance data were recorded using a 4.2 mm diameter catheter housing 36 circumferential pressure sensors. Remifentanil significantly shortened the time period of UES opening (p<0.001) and increased residual UES pressure (p=0.003). At the level of the hypopharynx, remifentanil significantly shortened the time latency from maximum bolus distension to peak contraction (p=0.004) and significantly increased intrabolus distension pressure (p=0.024). Novel mechanical states analysis revealed that the latencies between the different phases of the stereotypical UES relaxation sequence were shortened by remifentanil. Reduced duration of bolus flow during shortened UES opening in concert with increased hypopharyngeal distension pressures are mechanically consistent with increased flow resistance due to a more rapid bolus flow rate. These biomechanical changes are congruent with modification of the physiologic neuro-regulatory mechanism governing accommodation to bolus volume.
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