NOD1 mediates interleukin-18 processing in epithelial cells responding to Helicobacter pylori infection in mice.

The interleukin-1 family members, IL-1ß and IL-18, are processed into their biologically active forms by multi-protein complexes, known as inflammasomes. Although the inflammasome pathways that mediate IL-1ß processing in myeloid cells have been defined, those involved in IL-18 processing, particularly in non-myeloid cells, are still not well understood. Here we report that the host defence molecule NOD1 regulates IL-18 processing in mouse epithelial cells in response to the mucosal pathogen, Helicobacter pylori. Specifically, NOD1 in epithelial cells mediates IL-18 processing and maturation via interactions with caspase-1, instead of the canonical inflammasome pathway involving RIPK2, NF-κB, NLRP3 and ASC. NOD1 activation and IL-18 then help maintain epithelial homoeostasis to mediate protection against pre-neoplastic changes induced by gastric H. pylori infection in vivo. Our findings thus demonstrate a function for NOD1 in epithelial cell production of bioactive IL-18 and protection against H. pylori-induced pathology.

A novel technique for post-pyloric feeding tube placement in critically ill patients: a pilot study.

Delivery of enteral nutrition in critically ill patients is often hampered by gastric stasis necessitating direct feeding into the small intestine. Current techniques for placement of post-pyloric feeding catheters are complex, time consuming or both, and improvements in feeding tube placement techniques are required. The Cathlocator is a novel device that permits real time localisation of the end of feeding tubes via detection of a magnetic field generated by a small electric current in a coil incorporated in the tip of the tube. We performed a pilot study evaluating the feasibility of the Cathlocator system to guide and evaluate the placement of (1) nasoduodenal feeding tubes, and (2) nasogastric drainage tubes in critically ill patients with feed intolerance due to slow gastric emptying. A prospective study of eight critically ill patients was undertaken in the intensive care unit of a tertiary hospital. The Cathlocator was used to (1) guide the positioning of the tubes post-pylorically and (2) determine whether nasogastric and nasoduodenal tubes were placed correctly. Tube tip position was compared with data obtained by radiology. Data are expressed as median (range). Duodenal tube placement was successful in 7 of 8 patients (insertion time 12.6 min (5.3-34.4)). All nasogastric tube placements were successful (insertion time 3.4 min (0.6-10.0)). The Cathlocator accurately determined the position of both tubes without complication in all cases. The Cathlocator allows placement and location of an enteral feeding tube in real time in critically ill patients with slow gastric emptying. These findings warrant further studies into the application of this technique for placement of post-pyloric feeding tubes.

Cefazolin does not accelerate gastric emptying in the critically ill.

OBJECTIVE: To evaluate the effect of intravenous cefazolin on gastric emptying measured by the C-13 octanoic acid breath test. DESIGN: Prospective, double-blind, cross-over, randomised, placebo-controlled trial. SETTING: Mixed multidisciplinary intensive care unit in a university hospital. PATIENTS: Fourteen critically ill, mechanically ventilated patients. INTERVENTIONS: After a 4-h fast patients received either 50 mg cefazolin or 20 ml saline over 20 min immediately prior to measurement of gastric emptying. The next day the study was repeated with the alternative therapy. MEASUREMENTS AND RESULTS: Breath samples were analysed for the concentration of (13)CO2 by mass spectrometer, and the gastric emptying coefficient (GEC) and half-emptying time (t(50)) were calculated. Results are mean (standard deviation). Data were analysed with the paired t-test (saline vs cefazolin). Two patients were excluded for technical problems. Twelve patients remained (six male/six female), aged 57 (+/-16) years, with an APACHE II score of 20 (+/-8). Both GEC and t(50) were unchanged after administration of cefazolin compared with placebo (t(50) cefazolin, 138 (+/-54) vs saline 122 (+/-46) min, P=0.32; GEC cefazolin 3.27 (+/-0.83) vs saline 3.55 (+/-0.6), P=0.24). Two patients had abnormal t(50) after saline and five after cefazolin. There was no order effect of the study day. CONCLUSION: In mechanically ventilated patients, cefazolin had no effect on gastric emptying. These data do not support the use of low-dose cefazolin as a pro-kinetic agent in critically ill patients.