Inflammatory mechanisms in acute pancreatitis

Acute pancreatitis is an inflammatory condition. It is associated with a systemic inflammatory response, the degree of which appears to correlate with the severity of the illness. The role of circulating leucocytes and their production of cytokines in the development of severe acute pancreatitis is unknown. Monocytes are believed to be a major source of pro-inflammatory cytokines, but lymphocytes and endothelial cells also produce such cytokines. These cell types, in particular lymphocytes, also produce a variety of down-regulatory signals so that monocytes, lymphocytes and endothelial cells interact to produce a net systemic inflammatory signal, influenced further by the varying degree of lymphocyte sub-populations to undergo blastogenesis in response to inflammation. The focus of this thesis is on pro-inflammatory cytokines and their release in vitro from peripheral blood mononuclear cells (PBMCs) isolated from patients with acute pancreatitis.On admission to hospital, patients with acute pancreatitis demonstrated increased interleukin-6 and interleukin-8 release but not tumour necrosis factor-a release from isolated PBMCs compared with healthy volunteers. The severity of the disease was not related to the level of cytokine release from a standard cell number. However, when allowance was made for the variation in PBMC numbers in the blood, the estimated IL-6 and IL-8 release per unit of blood was greater in those patients with severe disease compared with those with mild disease. Severe disease is also characterised by a more prolonged duration of increased pro-inflammatory cytokine release compared with patients with mild disease. Products of the cyclooxygenase pathway play a down-regulatory role in PBMCs in patients with acute pancreatitis as indomethacin (a cyclo-oxygenase inhibitor) had no significant effect on pro-inflammatory cytokine release by PBMCs isolated from healthy volunteers, but increased IL-6 and IL-8 release by PBMCs isolated from patients with both mild and severe disease. PBMC pro-inflammatory cytokine release remains sensitive to the down-regulatory action of the T-cell regulatory cytokines, interleukin-4 and interleukin-10. Lymphocyte proliferation (as measured by thymidine incorporation) is impaired in acute pancreatitis and correlates with the severity of the disease. Following the successful isolation and culture of human umbilical vein endothelial cells, IL-4 and IL-10 (in contrast to their inhibitory action on PBMCs), produce a dose dependent increase in endothelial cell IL-6 and IL-8 release. TNFa is often undetectable in patients with acute pancreatitis on admission, even in severe disease. However, elevation in the serum concentration of soluble TNFa receptors would suggest significant TNFa-induced inflammation early in the course of the disease. Glutamine is a conditionally essential amino acid in patients with severe acute pancreatitis and is important for immune function. A double blind, randomised controlled trial of glutamine supplemented versus conventional total parenteral nutrition in patients with severe acute pancreatitis demonstrated a trend towards improved lymphocyte proliferation in the glutamine supplemented group. Furthermore, PBMC IL-8 release but not TNFa and IL-6 release was significantly reduced over the study period.Severe acute pancreatitis is associated with prolonged PBMC pro¬ inflammatory cytokine release and impaired lymphocyte proliferation. However, these cells remain sensitive to the down-regulatory action of T-cell cytokines in vitro, but the exogenous administration of these cytokines may have an unpredictable clinical effect because of their different actions on various cell types. More general methods of immuno-modulation, such as the exogenous administration of glutamine may have therapeutic benefit in patients with severe acute pancreatitis

Enteral nutrition in the critically ill: A prospective survey in an Australian intensive care unit

Publisher's copy made available with the permission of the publisher © Australian Society of AnaesthetistsNutritional support is routine practice in critically ill patients and enteral feeding is preferred to the parenteral route. However this direct delivery of nutrients to the gut is potentially ineffective for a variety of reasons. We performed a prospective audit of 40 consecutive intensive care patients to determine whether enteral feeding met the nutritional requirements of our patients. The ideal requirements for each patient were calculated using the Harris-Benedict equation with an adjustment determined by the patient’s diagnosis. We compared the amount of feed delivered with the daily requirements over a seven-day period. Successful feeding was defined as the achievement of 90% of the ideal calorie requirement for two consecutive days. The mean calculated (±SD) energy requirement was 9566kJ (±2586). Patients received only 51% (SD 38) of their energy requirements throughout the study period. Only 10 patients (25%)were successfully fed for at least any two-day period in the seven days. Feeding was limited mainly by gastrointestinal dysfunction or by the need to fast the patient for medical, surgical and airway procedures. Success of feeding was not related to the use of sedative or paralysing agents and had no correlation with plasma albumin concentration. There was no difference in the volume of feed delivered to patients who survived or died. Prokinetic agents were used in 25 patients and in these patients there was a trend towards improved delivery of feed.I. De Beaux, M. Chapman, R. Fraser, M. Finnis, B. De Keulenaer, D. Liberalli, M. Satanekhttp://www.aaic.net.au/Article.asp?D=200111

Protracted diagnosis of ACNES: a costly exercise

This case report summarizes the course of events leading to diagnosis and eventual repair of anterior cutaneous nerve entrapment syndrome (ACNES) in a 58-year-old female. The time period elapsing from initial symptoms to final operative repair was 9 months. The diagnosis was missed by both medical and surgical specialists despite multiple outpatient appointments, investigative procedures and a battery of laboratory tests. The diagnosis of ACNES was first considered when reviewed by a hernia surgeon and subsequently confirmed following open exploration of the anterior abdominal wall. The nerve was released and pain symptoms resolved. Access to the NHS Scotland ISD register permitted an economic analysis of the diagnostic services utilized for this patient and these totalled nearly £11 500. At a time when the NHS is focused on cost effectiveness, this particular sequence of investigations illustrates a protracted and costly diagnostic pathway

Hernia Basecamp—A Free to Use, Online Hernia Learning Platform. Analysis of Its Use Since Launch in June 2021

Introduction: Hernia Basecamp is an online learning platform hosted within the WebSurg website. One of the drivers of its development was to cover the syllabus of the UEMS AWS examination, but it is a learning resource in its own right. There are currently 205 video lectures, with a number of them selected to create 10 modules of 3 h each with UEMS CME accreditation. The aim of this study was to review the Hernia Basecamp usage since launch in June 2021.Methods: The Hernia Basecamp WebSurg platform was interrogated using Matomo Analytics in January 2023 (19 month period since launch). Data on the number of visits, pages looked at and time spent on the platform per visit, along with the number of CME modules taken and passed were collected.Results: Users from 146 countries visited the Hernia Basecamp site 17,171 times (6,586 times, 38.4% in first 9 months). The top 5 countries by visitors were the United Kingdom, Mexico, Spain, United States and Germany (accounting for 29.4% of the visits). The average time spent per visit was 11 min 37 s (range: 47 s–49 min 4 s), and the number of pages/videos viewed per visit was 8.1 (range: 2–21). The number of UEMS CME modules taken was 675, and 326 (48%) of these tests were passed.Conclusion: In the first 19 months from launch, Hernia Basecamp provided over 3,000 h of hernia education. The UEMS approved CME accreditation tests were commonly used