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Chemokines promote tumour progression by enhancing proliferation and modifying the immune response. The purpose of this study was to test the hypothesis that CCL2 monocyte chemotactic protein-1 (MCP-1) contributes to the progression of colorectal cancer by influencing the number and distribution of tumour associated macrophages (TAMs). Chemokine expression was assessed in human colorectal adenocarcinomas by ribonuclease protection assay (RPA). Colonic adenocarcinoma cell lines were used to assess chemokine production by enzyme linked immunosorbant assay (ELISA), and Boyden microchemotaxis assays were performed to determine cell line supernatant monocyte chemotactic activity. CCL2 production was assessed in paraffin embedded tumour samples by immunohistochemistry. Finally, the number of macrophages and their distribution was determined in the same colorectal adenocarcinomas and compared with CCL2 expression and tumour stage. Results showed that CCL2 produced by cell lines induced monocyte chemoattraction, the expression of this chemokine in solid cancers increased with tumour stage (P < 0.05) and immunohistochemistry localized production to tumour cells. Analysis of the macrophage infiltrate showed that the accumulation was significantly greater in tumours than controls (P < 0.005) and within tumours it was greatest in necrotic regions (median 44,600 per mm(3)). Macrophage accumulation increased with tumour stage and correlated with CCL2 expression (r(s) = 0.8). CXCL8 interleukin 8 (IL-8), a potent angiogenic factor and growth factor, was expressed in all tumours and cell lines. It is concluded that CCL2 induces the accumulation of tumour promoting TAMs in human colorectal cancer and represents a therapeutic target to modify the macrophage response and direct immune mediated therapy.

We have defined the host leukocyte infiltrate in epithelial ovarian tumors and related this to the expression of C-C chemokines. Immunohistochemical analysis of 20 paraffin-embedded biopsies showed that the infiltrate was primarily composed of CD68+ macrophages and CD8+/CD45RO+ T cells (median values, 3700 cells/mm3 and 2200 cells/mm3, respectively). Natural killer cells, B cells, and mast cells occurred in lower numbers (median values, 0 to 200 cells/mm3). Eosinophils were rarely seen and neutrophils were mainly confined to blood vessels. More infiltrating cells were found in stromal than in tumor areas. Only macrophages occurred in significant numbers in areas of necrosis (P < 0.0005). Using in situ hybridization to mRNA, we examined expression of the chemokines MCP-1, MIP-1 alpha, MIP-1 beta, and RANTES. MCP-1 and MIP-1 alpha were expressed by significantly more cells than MIP-1 beta and RANTES (P < 0.005). In tumor epithelial areas, the predominant chemokine was MCP-1. MCP-1 and MIP-1 alpha were the predominant stromal chemokines. A significant correlation was found between the total number of CD8+ T cells and the number of cells expressing MCP-1 (rs = 0.63 and P < 0.003, respectively) and between the CD8+ population and RANTES-expressing cells (rs = 0.6 and P < 0.003). A correlation was also found between CD68+ macrophages and the number of cells expressing MCP-1 (rs = 0.50 and P = 0.026). We suggest that MCP-1 may be responsible for the leukocyte infiltrate in ovarian carcinomas, but the expression of other chemokines may determine its exact nature.

IntroductionAntibiotic therapy is routinely used to eradicate Helicobacter pylori (Hp) infection, but emerging antibiotic resistance is a considerable concern. This study aimed to determine the prevalence of antibiotic resistance in high-risk patients undergoing upper gastrointestinal (GI) endoscopy and to identify potential predictive factors.MethodsThe retrospective study cohort comprised of all patients with recurrent/previous Hp infection undergoing upper GI endoscopy at the Royal Free Hospital (RFH), London between 2009 and 2019. Demographic, clinical, socioeconomic data and self-reported ethnic origin were retrieved from the medical records. Deprivation scores were based on postcode using the 2019 English Indices of Deprivation and decile rankings. The results of gastro/duodenal biopsy microscopy, culture and sensitivity testing were retrieved.ResultsA total of 408 patients (60% female, mean±1SD age 40.9±20.8 yr) were included; 118 (28.9%) were Hp culture positive while 290 were culture negative. There were no age or sex differences between the two cohorts; significantly fewer Hp positive patients were Caucasian (28% vs. 43%; p=0.039) and significantly more were classified as deprived (68% vs. 57%; p=0.031). Non-Caucasian origin (p=0.040) and greater deprivation (p=0.031) were significant independent predictors of Hp infection. Antibiotic resistance profiles were available in 115 patients; of these eight were fully sensitive but 107 (93.0%) exhibited antibiotic resistance, most commonly to metronidazole (100/111;90.1%) or clarithromycin (82/115;71.3%) or both (75/111;67.6%); resistance was also observed to tetracycline (3/113; 2.7%); amoxicillin (9/108; 8.3%); levofloxacin (20/111;18.0%) and rifabutin (8/26;30.8%). Overall, 81/107 (68.6%) cultures exhibited resistance to two or more antibiotics. Older age (p=0.009), greater deprivation (p=0.002), Caucasian origin (p=0.027) and use of PPIs (p=0.030) were significant independent predictors of antibiotic resistance but the number of failed eradication episodes was not.ConclusionNon-Caucasian origin and greater deprivation were identified as independent risk factors for the development of Hp infection while Caucasian origin, greater deprivation, older age and use of PPIs were independent risk factors for the development of antibiotic resistance. High levels of resistance were observed to the commonly used first and second line antibiotics in the majority of culture positive patients. In consequence wider use of culture and sensitivity testing of gastric biopsies in Hp positive patients should be advocated.

IntroductionAcute upper gastrointestinal bleeding (AUGIB) is a common complication of peptic ulcer disease (PUD) defined as not only peptic ulceration but also erosive gastritis and duodenitis, Helicobacter pylori (H. pylori) infection is the major cause of PUD. NICE guidelines recommend that patients identified with PUD should be tested and treated for H pylori if infected. Post-eradication testing is mandated to confirm successful eradication. The aim of this study was to determine compliance with national guidelines for the management of H. pylori in those with PUD-associated AUGIB.MethodsRetrospective data were collected on all patients presenting to the Royal Free Hospital, London, with non-variceal AUGIB between 1 January and 31 December 2017. Prospective data were collected between 1 February and 1 April 2018. Compliance with guidelines was judged using predetermined criteria and classified as: poor (<67% compliance); moderate (67–75%); good (>75%); or excellent (>90%).ResultsA total of 203 patients presented with non-variceal AUGIB during 2017, of whom 148 underwent endoscopy. Sixty-seven of those endoscoped met criteria for H. pylori testing but only 35 (52.2%) were investigated despite an absence of active bleeding or high-risk stigmata (compliance poor) (table 1). Of the 32 cases not tested, 22 exhibited overt ulceration at endoscopy, with the remaining cases demonstrating erosive changes. Four of the 55 non-endoscoped patients were tested for H pylori by other means. Overall, 15 (38.5%) of the 39 patients investigated tested positive for H pylori; 14 (93.3%) were prescribed eradication therapy (compliance excellent) while a further five patients were treated empirically. Of the 19 treated patients, only nine (47.4%) underwent post-eradication testing (compliance poor); all however tested negative. Prospective compliance rates in 36 patients exhibited similar poor compliance although samples were small (table 1).Abstract PTU-066 Table 1Management of H. pylori and compliance with associated NICE guidelines Management Step NICE Guideline Study Eligible (n) Performed (n) Compliance (%) Endoscopic detection Test for H. pylori if evidence of PUD R 67 35 Poor (52.2%) P 9 5 Poor (55.6%) Eradication therapy Offer those testing positive eradication therapy R 15 14 Excellent (93.3%) P 3 2 Poor (66.7%) Post-Eradication Testing Re-test using a C13 urea breath test. R 19 8 Poor (42.1%) P 2 0 Poor (0%) R = Retrospective, P = ProspectiveConclusionApproximately 50% of patients presenting with AUGIB with endoscopic features of PUD were not tested for H. pylori. Almost 40% of those who were tested were infected. Post-eradication investigation rates were particularly low. No clear explanation for this level of non-compliance with guidelines is apparent but enforcement is clearly warranted.

Introduction Helicobacter pylori (H. pylori) infection is the primary cause of peptic ulcer disease and is globally prevalent. Although eradication therapy is effective, emerging antibiotic resistance rates are of considerable concern. H. pylori infection is more prominent in deprived populations but the effects of ethnicity and social determinants of health on H. pylori resistance is unclear. The aim of this study was to establish the significance of socioeconomic and ethnic influences on H. pylori resistance.MethodsThe study population comprised of patients with recurrent/previous H. pylori infection plus current dyspeptic symptoms referred to the Royal Free Hospital, London, from 1 January 2017 to 1 September 2018, for endoscopic investigations. Gastro/duodenal biopsy samples were sent for culture and sensitivity testing. Demographic and clinical data were collected. Self-reported ethnic origin was recorded. Deprivation was analysed on a postcode basis, using the 2015 English Indices of Deprivation, by means of average decile ranking (1–10). Ethnic and socioeconomic differences between patients exhibiting resistance and those fully sensitive/culture negative were explored.ResultsA total of 107 patients, including 26 children, (61.7% female; median (range) age 37.5 (4–81) years; 43.9% Caucasian, 39.2% Asian), were sampled. Five were excluded (3 contaminated, 2 inappropriate samples). Forty of the remaining 102 samples yielded positive cultures; of these 6/40 were fully sensitive but 34 (33% of total sample) displayed antibiotic resistance, most commonly to metronidazole (91.2%), and/or clarithromycin (77.4%). Dual resistance was present in 52.9%. Resistance to amoxicillin (n=2) and levofloxacin (n=3) was also identified. The remaining 62 samples were culture negative. There were no differences in the age or sex distributions between the two cohorts. Likewise, there was no significant difference in the ethnic distribution between patients displaying antibiotic resistance and those sensitive/culture negative (Asian 47% vs. 35% Chi2P=0.25) (figure 1A). Deprivation analysis showed very similar average decile rankings in both patient groups although distribution was skewed to the deprived end of each domain in both (figure 1B).ConclusionOne-third of biopsy samples referred for sensitivity testing, during the study period, exhibited antibiotic resistance, most commonly to first and second line eradication therapies. No significant differences were observed in ethnicity or in deprivation between patients exhibiting resistance and those sensitive/culture negative. However, trends identified in this study need to be further explored.Abstract PTU-067 Figure 1 Comparative analysis of resistant vs. sensitive/no culture cohorts. (A) Ethnicity (B) Deprivation

Background: Diagnostic error is a significant problem in emergency medicine, where initial clinical assessment and decision making is often based on incomplete clinical information. Traditional computerised diagnostic systems have been of limited use in the acute setting, mainly due to the need for lengthy system consultation. We evaluated a novel web-based reminder system, which provides rapid diagnostic advice to users based on free text search terms. Methods: Clinical data collected from patients presenting to three emergency departments with acute medical problems were entered into the diagnostic system. The displayed results were assessed against the final discharge diagnoses for patients who were admitted to hospital (diagnostic accuracy) and against a set of “appropriate” diagnoses for each case provided by an expert panel (potential utility). Results: Data were collected from 594 patients (53.4% of screened attendances). Mean age was 49.4 years (95% CI 47.7 to 51.1) and the majority had significant past illnesses. Most were assessed first by junior doctors (70%) and 266/594 (44.6%) were admitted to hospital. Overall, the diagnostic system displayed the final discharge diagnosis in 95% of inpatients and 90% of “must-not-miss” diagnoses suggested by the expert panel. The discharge diagnosis appeared within the first 10 suggestions in 78% of cases. Conclusions: The Isabel diagnostic aid has been shown to be of potential use in reminding junior doctors of key diagnoses in the emergency department. The effects of its widespread use on decision making and diagnostic error can be clarified by evaluating its impact on routine clinical decision making.