CHARACTERISATION OF CYTOKINE GENE POLYMORPHISMS IN PATIENTS WITH ACUTE PANCREATITIS

Background and Aims Acute Pancreatitis is an inflammatory disorder of varied aetiology and outcome. Tumour necrosis factor (TNF) and interleukin-10 are important mediators of disease pathogenesis. To investigate if the TNF and IL-10 gene loci influence susceptibility to and severity of acute pancreatitis, 135 patients with acute pancreatitis, ethnically matched normal controls, and alcoholics without pancreatic disease were studied. Methods Aetiology was classified as being secondary to alcohol, gallstones, or idiopathic. Patients were stratified into groups according to disease severity by assigning an organ failure score. Three TNF microsatellite loci (TNFa, TNFb, and TNFc), the -308 polymorphism within the TNF gene, the IL-10.G microsatellite locus, and 3 hi-allelic polymorphisms in the 5' flanking region of the IL-l 0 gene were typed using the polymerase chain reaction. Results There was no difference in allelic frequency of any of the cytokine gene loci between groups stratified according to disease severity. When patients were stratified according to aetiology of disease there was a decrease in the frequency of the TNFa2 allele in those patients with alcoholic acute pancreatitis compared to controls (14.3 vs. 35.5%, χ²=7.24, p=0.007). There was also a reduction in the frequency of the IL-10.Gl3 allele in patients with alcoholic pancreatitis compared to controls (4.8 vs. 21.3%, χ² =6.46, p=0.011). Data is also presented showing that a number of haplotypes exist as well as linkage disequilibrium across all 4 loci of the IL-10 gene, which contrasts with findings from previous work. The 3 locus haplotypes GCC and ATA are in strongest linkage disequilibrium, as is the microsatellite allele G9 and -1117.A and G9 with the 3-locus haplotype ATA. Conclusions This work has identified an allele within the TNF gene locus, and an allele within the IL-1 0.G locus which have different frequencies in patients with alcohol induced acute pancreatitis compared to other aetiologies. This finding may in part explain individuals' differing susceptibility to the development of acute pancreatitis after excessive alcohol consumption. Haplotypes not previously described exist across the IL-10 locus

The value of routine histopathological examination of appendicectomy specimens

<p>Abstract</p> <p>Background</p> <p>Appendicectomy specimens removed from patients with suspected acute appendicitis often appear macroscopically normal but histopathological analysis of these cases may reveal a more sinister underlying pathology. We evaluated histopathological reports of 1225 appendicectomy specimens at the Norfolk and Norwich University Hospital (NNUH) over the past three years.</p> <p>Methods</p> <p>Histopathology reports for all appendices analysed at the NNUH between March 2003 and March 2006 were reviewed by examination of the case notes. The analysis focussed on the confirmation of acute appendicitis, incidental unexpected incidental findings other than inflammation, whether these abnormalities were suspected on gross examination at the time of surgery, and the effect on patient management and prognosis.</p> <p>Results</p> <p>The histopathology reports disclosed a variety of abnormal incidental lesions. Of the 1225 specimens, 46 (3.75%) revealed abnormal diagnoses other than inflammatory changes. Twenty-four (1.96%) of these were clinically significant and affected further patient management. Only two of these (0.16%) were suspected on macroscopic examination intra-operatively.</p> <p>Conclusion</p> <p>Twenty-four of the 1225 specimens (1.96%) had an impact on patient management or outcome and were not suspected on macroscopic examination at the time of surgery. These would have been missed had the specimens not been examined microscopically. The intra-operative diagnosis of the surgeon is therefore unreliable in detecting abnormalities of the appendix. This study supports the sending of all appendicectomy specimens for routine histopathological examination.</p

Multidimensional collaboration; reflections on action research in a clinical context

This paper reflects on the challenges and benefits of multidimensional collaboration in an action research study to evaluate and improve preoperative education for patients awaiting colorectal surgery. Three cycles of planning, acting,observing and reflecting were designed to evaluate practice and implement change in this interactive setting, calling for specific and distinct collaborations. Data collection includes: observing educational interactions; administering patient evaluation questionnaires; interviewing healthcare staff, patients and carers; patient and carer focus groups; and examining written and audiovisual educational materials. The study revolves around and depends on multi-dimensional collaborations. Reflecting on these collaborations highlights the diversity of perspectives held by all those engaged in the study and enhances the action research lessons. Successfully maintaining the collaborations recognises the need for negotiation, inclusivity, comprehension, brokerage,and problem-solving. Managing the potential tensions is crucial to the successful implementation of changes introduced to practice and thus has important implications for patients’ well-being. This paper describes the experiences from an action research project involving new and specific collaborations, focusing on a particular healthcare setting. It exemplifies the challenges of the collaborative action research process and examines how both researchers and practitioners might reflect on the translation of theory into educational practices within a hospital colorectal department. Despite its context-specific features, the reflections on the types of challenges faced and lessons learned provide implications for action researchers in diverse healthcare settings across the world

Canonical Wnt signals combined with suppressed TGFβ/BMP pathways promote renewal of the native human colonic epithelium

Background: A defining characteristic of the human intestinal epithelium is that it is the most rapidly renewing tissue in the body. However, the processes underlying tissue renewal and the mechanisms that govern their coordination have proved difficult to study in the human gut. Objective: To investigate the regulation of stem cell-driven tissue renewal by canonical Wnt and TGFβ/bone morphogenetic protein (BMP) pathways in the native human colonic epithelium. Design: Intact human colonic crypts were isolated from mucosal tissue samples and placed into 3D culture conditions optimised for steady-state tissue renewal. High affinity mRNA in situ hybridisation and immunohistochemistry were complemented by functional genomic and bioimaging techniques. The effects of signalling pathway modulators on the status of intestinal stem cell biology, crypt cell proliferation, migration, differentiation and shedding were determined. Results: Native human colonic crypts exhibited distinct activation profiles for canonical Wnt, TGFβ and BMP pathways. A population of intestinal LGR5/OLFM4-positive stem/progenitor cells were interspersed between goblet-like cells within the crypt-base. Exogenous and crypt cell-autonomous canonical Wnt signals supported homeostatic intestinal stem/progenitor cell proliferation and were antagonised by TGFβ or BMP pathway activation. Reduced Wnt stimulation impeded crypt cell proliferation, but crypt cell migration and shedding from the crypt surface were unaffected and resulted in diminished crypts. Conclusions: Steady-state tissue renewal in the native human colonic epithelium is dependent on canonical Wnt signals combined with suppressed TGFβ/BMP pathways. Stem/progenitor cell proliferation is uncoupled from crypt cell migration and shedding, and is required to constantly replenish the crypt cell population

Fasting and surgery timing (FaST) audit

Background & aimsInternational guidance advocates the avoidance of prolonged preoperative fasting due to its negative impact on perioperative hydration. This study aimed to assess the adherence to these guidelines for fasting in patients undergoing elective and emergency surgery in the East Midlands region of the UK.MethodsThis prospective audit was performed over a two-month period at five National Health Service (NHS) Trusts across the East Midlands region of the UK. Demographic data, admission and operative details, and length of preoperative fasting were collected on adult patients listed for emergency and elective surgery.ResultsOf the 343 surgical patients included within the study, 50% (n = 172) were male, 78% (n = 266) had elective surgery and 22% (n = 77) underwent emergency surgery. Overall median fasting times (Q1, Q3) were 16.1 (13.0, 19.4) hours for food and 5.8 (3.5, 10.7) hours for clear fluids. Prolonged fasting >12 h was documented in 73% (n = 250) for food, and 21% (n = 71) for clear fluids. Median fasting times from clear fluids and food were longer in the those undergoing emergency surgery when compared with those undergoing elective surgery: 13.0 (6.4, 22.6) vs. 4.9 (3.3, 7.8) hours, and 22.0 (14.0, 37.4) vs. 15.6 (12.9, 17.8) hours respectively, p < 0.0001.ConclusionsDespite international consensus on the duration of preoperative fasting, patients continue to fast from clear fluids and food for prolonged lengths of time. Patients admitted for emergency surgery were more likely to fast for longer than those having elective surgery

Identification of Surgeon Burnout via a Single-Item Measure

BackgroundBurnout is endemic in surgeons in the UK and linked with poor patient safety and quality of care, mental health problems, and workforce sustainability. Mechanisms are required to facilitate the efficient identification of burnout in this population. Multi-item measures of burnout may be unsuitable for this purpose owing to assessment burden, expertise required for analysis, and cost.AimsTo determine whether surgeons in the UK reporting burnout on the 22-item Maslach Burnout Inventory (MBI) can be reliably identified by a single-item measure of burnout.MethodsConsultant (n = 333) and trainee (n = 217) surgeons completed the MBI and a single-item measure of burnout. We applied tests of discriminatory power to assess whether a report of high burnout on the single-item measure correctly classified MBI cases and non-cases.ResultsThe single-item measure demonstrated high discriminatory power on the emotional exhaustion burnout domain: the area under the curve was excellent for consultants and trainees (0.86 and 0.80), indicating high sensitivity and specificity. On the depersonalisation domain, discrimination was acceptable for consultants (0.76) and poor for trainees (0.69). In contrast, discrimination was acceptable for trainees (0.71) and poor for consultants (0.62) on the personal accomplishment domain.ConclusionsA single-item measure of burnout is suitable for the efficient assessment of emotional exhaustion in consultant and trainee surgeons in the UK. Administered regularly, such a measure would facilitate the early identification of at-risk surgeons and swift intervention, as well as the monitoring of group-level temporal trends to inform resource allocation to coincide with peak periods

Burnout Among Surgeons in the UK During the COVID-19 Pandemic: A Cohort Study

BackgroundSurgeon burnout has implications for patient safety and workforce sustainability. The aim of this study was to establish the prevalence of burnout among surgeons in the UK during the COVID-19 pandemic.MethodsThis cross-sectional online survey was set in the UK National Health Service and involved 601 surgeons across the UK of all specialities and grades. Participants completed the Maslach Burnout Inventory and a bespoke questionnaire. Outcome measures included emotional exhaustion, depersonalisation and low personal accomplishment, as measured by the Maslach Burnout Inventory-Human Services Survey (MBI-HSS).ResultsA total of 142 surgeons reported having contracted COVID-19. Burnout prevalence was particularly high in the emotional exhaustion (57%) and depersonalisation (50%) domains, while lower on the low personal accomplishment domain (15%). Burnout prevalence was unrelated to COVID-19 status; however, the greater the perceived impact of COVID-19 on work, the higher the prevalence of emotional exhaustion and depersonalisation. Degree of worry about contracting COVID-19 oneself and degree of worry about family and friends contacting COVID-19 was positively associated with prevalence on all three burnout domains. Across all three domains, burnout prevalence was exceptionally high in the Core Trainee 1–2 and Specialty Trainee 1–2 grades.ConclusionsThese findings highlight potential undesirable implications for patient safety arising from surgeon burnout. Moreover, there is a need for ongoing monitoring in addition to an enhanced focus on mental health self-care in surgeon training and the provision of accessible and confidential support for practising surgeons

How may action research help patients awaiting colorectal cancer surgery to regain a sense of control over their lives?

How may action research help patients awaiting colorectal cancer surgery to regain a sense of control over their lives? Gregory S, Poland F, Spalding N, Sargen K, McCulloch J, Vicary P Abstract The educational process within the colorectal unit varies widely according to patient diagnosis, proposed surgery, and further treatments, and is provided by diverse healthcare professionals along their care pathway. Relatively few preoperative education services for colorectal patients have been formally evaluated. An action research-based evaluation of a preoperative education service examined whether and how patients and carers might see the service as beneficial and relevant and what they might identify as potential improvements. An action research study was carried out using three cycles of planning, acting, observing and reflecting on changes. Themes relevant to informing changes in education provision were taken to a healthcare staff decision-making meeting to inform the next action cycle. Themes identified in patient, carer and staff views and suggestions focused on potential ways they could play a more active role in preparing for surgery and enhancing their own recovery to self-manage their lives. These included patient journey timescales, stoma management, normalising bodily changes, dietary changes and resuming normal occupations. Identifying information which was meaningful to their lifeworlds was seen as critical for enabling patients to regain a sense of control after major disruption to their biographies and sense of self following a diagnosis of cancer requiring colorectal surgery. Action research provided ways to represent and integrate these within clinical practice in the innovative development (including through poetic narratives), content, timing and communication of preoperative education. This abstract outlines independent research commissioned by the National Institute for Health Research (NIHR) under the RfPB programme Ref: PB-PG-1207-13321. The views expressed are those of the authors and not necessarily those of the NHS, the NIHR or the Department of Health