Acute sedation-associated complications in GI endoscopy (ProSed 2 Study): results from the prospective multicentre electronic registry of sedation-associated complications.

OBJECTIVES: Sedation has been established for GI endoscopic procedures in most countries, but it is also associated with an added risk of complications. Reported complication rates are variable due to different study methodologies and often limited sample size. DESIGNS: Acute sedation-associated complications were prospectively recorded in an electronic endoscopy documentation in 39 study centres between December 2011 and August 2014 (median inclusion period 24 months). The sedation regimen was decided by each study centre. RESULTS: A total of 368 206 endoscopies was recorded; 11% without sedation. Propofol was the dominant drug used (62% only, 22.5% in combination with midazolam). Of the sedated patients, 38 (0.01%) suffered a major complication, and overall mortality was 0.005% (n=15); minor complications occurred in 0.3%. Multivariate analysis showed the following independent risk factors for all complications: American Society of Anesthesiologists class >2 (OR 2.29) and type and duration of endoscopy. Of the sedation regimens, propofol monosedation had the lowest rate (OR 0.75) compared with midazolam (reference) and combinations (OR 1.0-1.5). Compared with primary care hospitals, tertiary referral centres had higher complication rates (OR 1.61). Notably, compared with sedation by a two-person endoscopy team (endoscopist/assistant; 53.5% of all procedures), adding another person for sedation (nurse, physician) was associated with higher complication rates (ORs 1.40-4.46), probably due to higher complexity of procedures not evident in the multivariate analysis. CONCLUSIONS: This large multicentre registry study confirmed that severe acute sedation-related complications are rare during GI endoscopy with a very low mortality. The data are useful for planning risk factor-adapted sedation management to further prevent sedation-associated complications in selected patients. TRIAL REGISTRATION NUMBER: DRKS00007768; Pre-results.

Inhibition of p38/Mk2 signaling pathway improves the anti-inflammatory effect of WIN55 on mouse experimental colitis.

P38/Mk2 (mitogen-activated protein kinase (MAPK)-activated protein kinase-2, also known as MAKAP kinase-2) is a member of the mitogen-activated protein kinases (MAPKs) family, and participates in inflammatory responses directly or indirectly. WIN55, 212-2 (WIN55) is a synthetic non-selective agonist of cannabinoid (CB) receptors with remarkable anti-inflammatory properties. This study was to explore the roles of WIN55 and p38/Mk2 signaling pathway in dextran sodium sulfate (DSS)-induced mouse colitis and ascertain their anti-inflammatory mechanisms. Colitis was induced in C57BL Mk2 gene homozygous deletion (Mk2-/-) and wild-type mice by replacing the drinking water with 4% DSS solution for 7 days. DSS-treated mice developed bloody stool, weight loss, and eye-visible multiple bleeding ulcers on colon mucosa. The mRNA expressions levels of TNF-α and IL-6, as well as the protein levels of p38 and its phosphorylated form (p-p38), were upregulated in the colon. The plasma levels of TNF-α, IL-6, cytokine-induced neutrophil chemoattractant-1 (CINC-1), monocyte chemoattractant protein-1 (MCP-1), and lung myeloperoxidase (MPO) activities were raised; however, all these changes were less severe in Mk2-/- mice. After WIN55 intervention, the Mk2-/- mice recovered faster and better from the induced colitis than their wild-type counterparts. The results indicate that the Mk2 homozygous deletion in mice impedes the induction of experimental colitis by DSS, confirming the notion that p38/Mk2 is involved in this inflammatory response. WIN55 protects mice against DSS-induced colitis, in particular when the p38/Mk2 pathway is obstructed, implying that the activation of CB system, together with blocking of p38/Mk2 pathway, serves as a potential drug target for colitis treatment.

Comparison of diagnostic accuracy and interpretation times for a standard and an advanced 3D visualisation technique in CT colonography.

OBJECTIVE: To compare the diagnostic accuracy of a standard bi-directional, three-dimensional (3D) CT colonography (CTC) fly-through (standard view, SV) with a unidirectional, 3D unfolding technique (panoramic view, PV). METHODS: 150 consecutive endoscopically-validated CTC patient datasets were retrospectively reviewed twice by two expert radiologists: first, with bidirectional SV, second, after 6-15 months, with unidirectional PV. Per-polyp sensitivities, percentage of visualised colonic mucosa, and reading times were calculated for both 3D visualisations. Results were tested for statistical significance by equivalence analysis for paired proportions and Student's paired t-test. RESULTS: In 81 patients, 236 polyps (101 adenomas, 135 non-adenomas) were detected. Sensitivities for polyps ≤5 mm, 6-9 mm and ≥10 mm were 60.1% (113/188), 92.9% (26/28) and 95.0% (19/20) with bidirectional SV, and 60.6% (114/188), 96.4% (27/28) and 95.0% (19/20) with unidirectional PV. Overall sensitivity for adenomas was 86.1% and 84.2% for SV and PV. Both methods provided equivalent polyp detection, with an equivalence limit set at 5%. PV and SV visualised 98.9 ± 1.1% (97.0-99.9%) and 96.2 ± 2.3% (91.4-98.8%) of the colonic mucosa (p > 0.05). Mean interpretation time decreased from 14.6 ± 2.5 (9.2-22.8) minutes with SV to 7.5 ± 3.2 (5.0-14.4) using PV (p < 0.0001). CONCLUSION: 3D CTC interpretation using unidirectional PV is equally as accurate, but significantly faster than an interpretation based on bidirectional SV.

Ascitic fluid and serum from rats with acute pancreatitis injure rat pancreatic tissues and alter the expression of heat shock protein 60.

Acute pancreatitis (AP) is an inflammatory process in which cytokines and chemokines are involved. After onset, extrapancreatic stimuli can induce the expression of cytokines in pancreatic acinar cells, thereby amplifying this inflammatory loop. To further determine the role and mechanism of irritating agents in the pathogenesis of AP, rat pancreatic tissues were stimulated with ascitic fluid (APa) and serum (APs) from rats with AP or with lipopolysaccharide (LPS). In addition, the alteration of heat shock protein 60 (HSP60) expression was evaluated. Rat pancreas was removed and meticulously snipped to fragments. The snips were cultured for up to 48 h. During this period, the tissue viability as well as amylase and TNF-alpha levels in the supernatant and the HSP60 expression in the pancreatic tissue before and after stimulation by APa, APs, and LPS were assayed time-dependently. At different time-points during the culture, the viability and the amylase activity in the pancreatic tissue remained largely stable. After stimulation with APa, APs, or LPS for 1 h, the pancreatic tissues showed some damage, and this was followed by a sharp decrease in the viability accompanied by increased levels of amylase and TNF-alpha in the culture medium 2 or 4 h after stimulation (p < 0.05). In contrast, both the HSP60 mRNA and protein levels had a relatively high expression in the freshly prepared tissue fragments (0 h). As the culturing period was extended, the expression of HSP60 mRNA decreased only slightly; at the same time, the HSP60 protein levels decreased over a prolonged culture time, significantly so from 12 through 48 h (p < 0.05). After stimulation with APs, APa, or LPS, both the expression of HSP60 mRNA and protein in the tissue fragments increased slightly at 1 h and decreased significantly thereafter at 2 and 4 h (p < 0.05). APa, APs, or LPS induce injuries on isolated pancreatic tissues, accompanied by an altered HSP60 expression pattern in a time-dependent manner.

Correlation of magnetic resonance enteroclysis (MRE) and wireless capsule endoscopy (CE) in the diagnosis of small bowel lesions in Crohn's disease.

BACKGROUND: The aim was to evaluate and compare the diagnostic performance of magnetic resonance enteroclysis (MRE) and wireless video capsule endoscopy (CE) in detecting and classifying small bowel Crohn's disease (CD) proximal to the terminal ileum. METHODS: Nineteen patients with histologically proven CD (M:F = 13:6; mean 34 years, range 17-65) were prospectively included in the study when presenting with clinical signs suggesting stricturing or inflammatory lesions of CD in the proximal small bowel. All patients underwent MRE with an infusion technique and were then admitted to CE. RESULTS: As for the presence or absence of pathology, results of MRE and CE were in total agreement for 44/52 (85%) evaluated segments. In judging lesion severity, MRE and CE yielded identical results in 29/52 (56%) segments. MRE underestimated pathology in 7/52 (14%) segments and revealed more severe pathology in 6/52 (12%) segments. CE identified subtle (n = 7) or severe (n = 2) mucosal pathology while MRE was normal. CE entirely missed severe inflammatory mural changes depicted in MRE in 1/52 (2%) segments. CONCLUSIONS: MRE and CE show good correlation in the detection and localization of inflammatory bowel disease. As for disease activity, MRE is inferior in the detection of superficial mucosal disease but reliably discloses the presence of severe inflammatory changes within the bowel wall and beyond, which may be underestimated from the endoscopic aspect of the mucosal surface. MRE helps to rule out severe stenoses that should be referred for immediate surgical intervention. In conclusion, both modalities are complementary and MRE should be used in more severe cases of Crohn's disease and in patients who might have involvement beyond the mucosa of the small bowel.