Consumer intention towards the phosphate-reduced processed meat products using the extended theory of planned behaviour.

Phosphates are essential for maintaining various quality attributes of processed meat products such as water-binding properties, texture and sensory properties and their removal would drastically change the products' technical and sensory qualities. Currently, meat industries are faced with the challenge of removing phosphates to address the consumers' demand to remove the negatively perceived synthetic additives from processed meat products. This study measured these consumers' purchase intention of phosphate-reduced processed meat products with different quality, using the extended theory of planned behaviour (TPB). An online survey was conducted among the consumers (n = 548) of the Republic of Ireland (ROI) to predict their knowledge and attitude towards phosphate additives. Analysis of the survey responses showed that about two-third of the participants consumed processed meat products 5-6 times per week. The results of multiple linear regression showed that the theory constructs attitude, subjective norms, perceived health risks significantly (P < 0.05) influenced the consumer behavioural intention whereas the perceived behavioural control (PBC) produced insignificant impacts. The results also revealed that the extended TPB model predicted the consumers' intention with better explanatory power (adjusted R2 = 0.46) than the original TPB model. In conclusion, various recommendations and implications were developed based on the results to improve the consumers' purchase intention of these products.

The Impact of the Covid-19 Pandemic on Food Consumers' Awareness of Antimicrobial Resistance, OneHealth, and Animal Welfare Information on Food Labels.

Covid-19 is a OneHealth crisis with far-reaching and unexpected impacts on many aspects of society. Previous OneHealth issues, such as antimicrobial resistance (AMR), have not received a similar level of attention or action from the public despite representing significant public health and economic threats to society. The current study aimed to explore whether the Covid-19 pandemic may act as a catalyst to increase public awareness related to OneHealth issues, in particular, AMR. This short paper presents overview findings from a survey carried out in September 2020 with a representative sample of food consumers on the island of Ireland (n = 972). The survey revealed Covid-19 had increased awareness of AMR amongst 47% of respondents; increased awareness of connected animal and human health amongst 43% of respondents; and increased awareness of animal welfare information on food labels amongst 34% of respondents. A cluster analysis revealed five distinct consumer segments impacted differently by Covid-19. These segments differed in their levels of objective and subjective knowledge of antibiotic use practises in farming, AMR risk perception, and attributions of responsibility for action on AMR. Findings are discussed with respect to future efforts by the agri-food sector to communicate with the public about AMR and responsible antibiotic use in farming, with particular emphasis on the implications for strategies that incorporate front-of-pack labelling.

Does clinical validation and the implementation of new models of outpatient service delivery have the potential to reduce waiting lists? A pilot study in Letterkenny University Hospital.

INTRODUCTION: The traditional outpatient paradigm of seeing patients prior to diagnostic tests and treatment is unsustainable without additional funding. New models of service delivery such as "one-stop clinics", direct access to diagnostics and advanced nurse practitioner (ANP)-led clinics have the potential to improve the efficiency of existing services. METHODS: To determine the most effective changes to improve service provision, the reasons for encounter (RFE) to a urology clinic were assessed using the International Classification Primary Care. To test these changes, a clinical validation process was performed on existing waiting patients waiting ≥ 15 months. Direct access to diagnostics and an ANP-led clinic were introduced. The impact of this validation process was measured prospectively using independently-collated National Treatment Purchase Fund waiting list data. RESULTS: From January to December 2017, 1114 new patients were referred. The 3 most frequent RFEs were haematuria, urinary frequency/urgency and cystitis and accounted for 48% of referrals overall. A new outpatient pathway, combining direct access to diagnostics and an ANP-led clinic, was implemented on 508 existing patients waiting ≥ 15 months. The validation process resulted in referral directly to a consultant-led clinic in 36%, to an ANP-led clinic in 12%, direct access to diagnostics in 38% and removal in 13%. This change was implemented in July 2017 and there was a 76% reduction in the number of patients waiting ≥ 12 months by December 2017. CONCLUSION: New models of outpatient service delivery have the potential to reduce existing waiting lists and could be implemented in other Irish hospital groups.

The transition to digital presentation of the diagnostic imaging domain of the Part IV examination of the National Board of Chiropractic Examiners.

OBJECTIVE: This article introduces changes made to the diagnostic imaging (DIM) domain of the Part IV of the National Board of Chiropractic Examiners examination and evaluates the effects of these changes in terms of item functioning and examinee performance. METHODS: To evaluate item function, classical test theory and item response theory (IRT) methods were employed. Classical statistics were used for the assessment of item difficulty and the relation to the total test score. Item difficulties along with item discrimination were calculated using IRT. We also studied the decision accuracy of the redesigned DIM domain. RESULTS: The diagnostic item analysis revealed similarity in item function across test forms and across administrations. The IRT models found a reasonable fit to the data. The averages of the IRT parameters were similar across test forms and across administrations. The classification of test takers into ability (theta) categories was consistent across groups (both norming and all examinees), across all test forms, and across administrations. CONCLUSION: This research signifies a first step in the evaluation of the transition to digital DIM high-stakes assessments. We hope that this study will spur further research into evaluations of the ability to interpret radiographic images. In addition, we hope that the results prove to be useful for chiropractic faculty, chiropractic students, and the users of Part IV scores.

Variables associated with successful performance on the National Board of Chiropractic Examiners Part IV examination.

OBJECTIVE: The objectives of this study were to (1) identify factors predictive of performance on the National Board of Chiropractic Examiners Part IV exam and (2) investigate correlations between the scores obtained in the Part I, Part II, Physiotherapy, and Part III exams and the Part IV examination. METHODS: A random sample of 1341 records was drawn from National Board of Chiropractic Examiners data to investigate the relationships between the scores obtained on the National Board of Chiropractic Examiners exams. A hierarchical multiple regression analysis related the performance on Part IV to examinee's gender, Part IV repeater status, and scores obtained on the Part I, Part II, Physiotherapy, and Part III exams. RESULTS: The analyses revealed statistical relations among all National Board of Chiropractic Examiners exams. The correlations between Part IV and Part I ranged from r = .31 to r = .4; between Part IV and Part II from r = .34 to r = .45. The correlation between Part IV and Physiotherapy was r = .44; between Part IV and Part III was r = .46. The strongest predictors of the Part IV score were found to be examinees' scores in Diagnostic Imaging, ß̂ = .19, p < .001; Chiropractic Practice, ß̂ = .17, p < .001; Physiotherapy, ß̂ = .15, p < .001; and the Part III exam ß̂ = .19, p < .001. CONCLUSIONS: Performance on the National Board of Chiropractic Examiners Part IV examination is related to the performance in all other National Board of Chiropractic Examiners exams.

Tumour vasculature immaturity, oxidative damage and systemic inflammation stratify survival of colorectal cancer patients on bevacizumab treatment.

Despite treatment of patients with metastatic colorectal cancer (mCRC) with bevacizumab plus chemotherapy, response rates are modest and there are no biomarkers available that will predict response. The aim of this study was to assess if markers associated with three interconnected cancer-associated biological processes, specifically angiogenesis, inflammation and oxidative damage, could stratify the survival outcome of this cohort. Levels of angiogenesis, inflammation and oxidative damage markers were assessed in pre-bevacizumab resected tumour and serum samples of mCRC patients by dual immunofluorescence, immunohistochemistry and ELISA. This study identified that specific markers of angiogenesis, inflammation and oxidative damage stratify survival of patients on this anti-angiogenic treatment. Biomarkers of immature tumour vasculature (% IMM, p=0.026, n=80), high levels of oxidative damage in the tumour epithelium (intensity of 8-oxo-dG in nuclear and cytoplasmic compartments, p=0.042 and 0.038 respectively, n=75) and lower systemic pro-inflammatory cytokines (IL6 and IL8, p=0.053 and 0.049 respectively, n=61) significantly stratify with median overall survival (OS). In summary, screening for a panel of biomarkers for high levels of immature tumour vasculature, high levels of oxidative DNA damage and low levels of systemic pro-inflammatory cytokines may be beneficial in predicting enhanced survival outcome following bevacizumab treatment for mCRC.

Deep anestrous mares under natural photoperiod treated with recombinant equine FSH (reFSH) and LH (reLH) have fertile ovulations and become pregnant.

The most common equine breeding practice to decrease the time to the first ovulation of the year is to use artificial lights starting December 1 in the Northern Hemisphere. It can take 60-90 d for this lighting regimen to induce a fertile ovulation. The success rate for pharmaceutical compounds to carry out the same process has been variable. One compound that did induce an early ovulation was recombinant equine follicle stimulating hormone (reFSH), but neither pregnancy nor cyclicity was established in that study. Starting on December 1, 20 deep-anestrous mares of light horse breeds (4-15 y old) with follicles ≤ 20 mm in diameter and progesterone < 1 ng/mL were maintained under natural photoperiod while 10 control mares were maintained under artificial photoperiod. Starting on February 6, treatment mares were randomly assigned to one of two groups: reFSH (n = 10) or reFSH/reLH (n = 10). Jugular blood samples were collected daily from all mares, and luteinizing hormone (LH), FSH, progesterone (P4), estradiol-17ß (E2) and immunoreactive (ir)-inhibin were analyzed by radioimmunoassay (RIA). When the largest follicle reached ≥32 mm in diameter, reFSH treatment was discontinued in both groups while reLH treatment continued in the reFSH/reLH group until a cohort of follicles reached ≥35 mm in diameter. Human chorionic gonadotropin (hCG) was administered intravenously (iv) to induce ovulation, and mares were bred to a fertile stallion every other day until ovulation. Mares receiving either reFSH or reFSH/reLH developed follicles ≥35 mm within 5-6 d of treatment compared with 15.8 ± 3.4 d in the control group. Both reFSH and reFSH/reLH induced ovulation in 100% of the mares within 10 d after treatment resulting in an 80% conception rate and a 70% pregnancy rate for both groups. Conception and pregnancy were designated as either presence of a 14 d old embryo (n = 16) or a fetal heartbeat at 24 d (n = 14), respectively. Only three mares in the control group ovulated within the same treatment period. Later ovulations in the control group resulted in 100% conception and pregnancy rates. At 25 d post-conception, treated mares that were pregnant (n = 7 per group) were administered prostaglandin (PGF2α) to terminate the pregnancy and later returned to estrus. Treatment with reFSH or reFSH/reLH given to deep-anestrous mares under natural photoperiod induced fertile ovulations that resulted in pregnancy and cyclicity when pregnancies were terminated.

Screening for mismatch repair deficiency in colorectal cancer: data from three academic medical centers.

Reflex immunohistochemistry (rIHC) for mismatch repair (MMR) protein expression can be used as a screening tool to detect Lynch Syndrome (LS). Increasingly the mismatch repair-deficient (dMMR) phenotype has therapeutic implications. We investigated the pattern and consequence of testing for dMMR in three Irish Cancer Centres (CCs). CRC databases were analyzed from January 2005-December 2013. CC1 performs IHC upon physician request, CC2 implemented rIHC in November 2008, and CC3 has been performing rIHC since 2004. The number of eligible patients referred to clinical genetic services (CGS), and the number of LS patients per center was determined. 3906 patients were included over a 9-year period. dMMR CRCs were found in 32/153 (21%) of patients at CC1 and 55/536 (10%) at CC2, accounting for 3% and 5% of the CRC population, respectively. At CC3, 182/1737 patients (10%) had dMMR CRCs (P < 0.001). Additional testing for the BRAF V600E mutation, was performed in 49 patients at CC3 prior to CGS referral, of which 29 were positive and considered sporadic CRC. Referrals to CGS were made in 66%, 33%, and 30% of eligible patients at CC1, CC2, and CC3, respectively. LS accounted for CRC in eight patients (0.8%) at CC1, eight patients (0.7%) at CC2, and 20 patients (1.2%) at CC3. Cascade testing of patients with dMMR CRC was not completed in 56%. Universal screening increases the detection of dMMR tumors and LS kindreds. Successful implementation of this approach requires adequate resources for appropriate downstream management of these patients.

The role of meat in strategies to achieve a sustainable diet lower in greenhouse gas emissions: A review.

Food consumption is responsible for a considerable proportion of greenhouse gas emissions (GHGE). Hence, individual food choices have the potential to substantially influence both public health and the environment. Meat and animal products are relatively high in GHGE and therefore targeted in efforts to reduce dietary emissions. This review first highlights the complexities regarding sustainability in terms of meat consumption and thereafter discusses possible strategies that could be implemented to mitigate its climatic impact. It outlines how sustainable diets are possible without the elimination of meat. For instance, overconsumption of food in general, beyond our nutritional requirements, was found to be a significant contributor of emissions. Non-voluntary and voluntary mitigation strategies offer potential to reduce dietary GHGE. All mitigation strategies require careful consideration but on-farm sustainable intensification perhaps offers the most promise. However, a balance between supply and demand approaches is encouraged. Health should remain the overarching principle for policies and strategies concerned with shifting consumer behaviour towards sustainable diets.

Victimisation in urban primary schools of high-poverty areas: associations with health-related quality of life, depression and social support.

BACKGROUND: Although a widespread issue, research on victimisation among primary school children in high-poverty regions is limited. The aim of this research was to explore victimisation incidence and associated mental health correlates from first-wave data of the 'Healthy Schools' programme in a high-poverty urban region. METHOD: The study explored victimisation incidences among 458 Irish primary school children and associations with depression, health-related quality of life (HRQoL) and social support. RESULTS: Victimisation (33.8%) was consistent with recent literature. On the stand-alone victimisation question, victims scored lower on all HRQoL subscales compared with nonvictims. Further categorisation revealed that frequent victims scored lower on four of these subscales, compared with nonvictims. Furthermore, over half of children felt that their school was not doing enough to combat school aggression. CONCLUSIONS: Although from a high-poverty area, rates were consistent with data from more affluent areas. Results stress an importance on specific school aggression behaviours when measuring victimisation rates, along with corresponding health consequences. Future research should continue to adopt the behaviour-based assessment of victimisation to provide an overall picture of the problem.

The climatic impact of food consumption in a representative sample of Irish adults and implications for food and nutrition policy.

OBJECTIVE: To evaluate the greenhouse gas emissions (GHGE) associated with the diet of Irish adults. DESIGN: GHGE were estimated by applying conversion factors to habitual food consumption data taken from the National Adult Nutrition Survey, which was representative of the population. Descriptive analyses were undertaken for GHGE for the total population, as well as accounting for energy misreporting and across categories of sociodemographic and socio-economic factors and tertiles of emissions. SETTING: Republic of Ireland. SUBJECTS: Adults aged 18-87 years (n 1500). RESULTS: The GHGE derived from daily dietary intakes was estimated as 6·5 kg of CO2 equivalents (CO2eq) per person. Males, younger consumers, those with secondary education and student employment status were associated with significantly higher GHGE. Red meat was the highest contributor to GHGE with 1646 g CO2eq arising from a mean intake of 47 g/d. Dairy and starchy staples were the next largest dietary GHGE sources, with mean daily emissions of 732 g CO2eq and 647 g CO2eq, respectively. The lowest emissions were associated with consumption of vegetables, fruits and legumes/pulses/nuts. CONCLUSIONS: Based on profiling using actual food consumption data, it is evident that one single measure is not sufficient and a range of evidence-based mitigation measures with potential to lower emissions throughout the food chain should be considered. The research contributes towards an improved understanding of the climatic impact of the dietary intakes of Irish adults and can serve to inform a sustainability framework to guide action in food and nutrition policy development.

Parenthood, Child Care, and Heroin Use: Outcomes After Three Years.

BACKGROUND: Internationally there is a lack of measurement on the impact of childcare on people who use drugs. OBJECTIVES: The aim of this article was to longitudinally measure drug use, familial and social status and criminal involvement between parents and nonparents who use heroin and have children in their care. METHODS: From 2003 to 2006, 404 participants were recruited to the Research Outcome Study in Ireland Evaluating Drug Treatment Effectiveness (ROSIE) as part of a longitudinal cohort study design. Participants completed the Maudsley Addiction Profile and 88% (n = 356) completed interviews at the 3-year period. One way between groups ANOVA with post hoc tests and backward, stepwise multiple regression were employed for analysis. RESULTS: At follow-up, parents who had children in their care used heroin (p = .004), illicit methadone (p ≤ .001) and cocaine (p = .024) on fewer days than those who had no children, or those who had children but did not have children in their care. These differences were not observed at intake. Living with someone at intake who used drugs was found to be significantly associated with increased heroin (p ≤ .001), benzodiazepine (p = .039), and tobacco (p = .030) use at 3 years. Furthermore, a change in childcare status to caring for a child was associated with increased cannabis use (p = .025). Conclusion/Importance: While caring for children was associated with reduced heroin use at 3 years, living with a person who used at intake removed this effect, thus indicating that while individual based addiction theories reflected observed outcomes, social network connectedness was more influential.

Enrichment of Inflammatory IL-17 and TNF-α Secreting CD4(+) T Cells within Colorectal Tumors despite the Presence of Elevated CD39(+) T Regulatory Cells and Increased Expression of the Immune Checkpoint Molecule, PD-1.

T cell infiltration into colorectal tumors has been shown to correlate with improved patient outcomes. However, more detailed information on the makeup and relationships between the infiltrating T cell subsets is lacking. We therefore correlated the extent of immune infiltration into colorectal tumors with the frequencies of various T cell subsets. We prospectively recruited 22 patients at the time of surgical resection for colorectal cancer. The Klintrup-Mäkinen (KM) score was used to estimate the extent of immune infiltration into colorectal tumors. The frequencies of CD4 and CD8 T cells that produced cytokines or expressed the inhibitory molecule programed cell death 1 (PD-1) were determined by flow cytometry in colorectal tumor and matched uninvolved colonic tissue. In addition, the frequency of CD4 regulatory T cell (Treg) subsets was determined. An increased frequency of CD4 T cells producing IL-17 (Th17 cells) was observed in colorectal tumor tissue compared with adjacent uninvolved tissue. These Th17 cells mostly coproduced TNF-α, but not IFN-γ. IL-17 expression correlated positively with TNF-α and IL-10. Increased expression of the immune checkpoint molecule PD-1 was found in colorectal tumors compared with adjacent uninvolved tissue. There was a negative correlation between expression of PD-1 and IFN-γ, but not IL-17, for both CD4(+) and CD8(+) T cells. CD4(+)CD25(+)CD127(lo) and CD4(+)CD25(+)CD127(lo)FoxP3(+)CD39(+) Treg cells were enriched in colorectal tumors. A positive correlation between KM score and percentage CD4(+)CD25(+)CD127(lo) Treg cells was observed in tumors, suggesting that increased immune infiltration is associated with an increased proportion of Treg cells. In addition, there was a negative correlation between the frequency of CD4(+)CD25(+)CD127(lo) Treg cells and the expression of IFN-γ and IL-2, but not IL-17, in tumors. Taken together, these data suggest that both PD-1 expressing T cells and Treg cells within the tumor may have a suppressive effect on T cells secreting IFN-γ, IL-2, or TNF-α, but not Th17 cells.

Predicting response to vascular endothelial growth factor inhibitor and chemotherapy in metastatic colorectal cancer.

BACKGROUND: Bevacizumab improves progression free survival (PFS) and overall survival (OS) in metastatic colorectal cancer patients however currently there are no biomarkers that predict response to this treatment. The aim of this study was to assess if differential protein expression can differentiate patients who respond to chemotherapy and bevacizumab, and to assess if select proteins correlate with patient survival. METHODS: Pre-treatment serum from patients with metastatic colorectal cancer (mCRC) treated with chemotherapy and bevacizumab were divided into responders and nonresponders based on their progression free survival (PFS). Serum samples underwent immunoaffinity depletion and protein expression was analysed using two-dimensional difference gel electrophoresis (2D-DIGE), followed by LC-MS/MS for protein identification. Validation on selected proteins was performed on serum and tissue samples from a larger cohort of patients using ELISA and immunohistochemistry, respectively (n = 68 and n = 95, respectively). RESULTS: 68 proteins were identified following LC-MS/MS analysis to be differentially expressed between the groups. Three proteins (apolipoprotein E (APOE), angiotensinogen (AGT) and vitamin D binding protein (DBP)) were selected for validation studies. Increasing APOE expression in the stroma was associated with shorter progression free survival (PFS) (p = 0.0001) and overall survival (OS) (p = 0.01), DBP expression (stroma) was associated with shorter OS (p = 0.037). Increasing APOE expression in the epithelium was associated with a longer PFS and OS, and AGT epithelial expression was associated with a longer PFS (all p < .05). Increasing serum AGT concentration was associated with shorter OS (p = 0.009). CONCLUSIONS: APOE, DBP and AGT identified were associated with survival outcomes in mCRC patients treated with chemotherapy and bevacizumab.

Determinants of short- and long-term survival from colorectal cancer in very elderly patients.

PURPOSE: Over 5100 colorectal cancers (CRCs) are diagnosed in the United Kingdom in 85 years and older age group per year but little is known of cancer progression in this group. We assessed clinical, pathological and molecular features of CRC with early and late mortality in such patients. METHODS: Data were analysed in relation to early mortality and long-term survival in 90 consecutive patients with CRC aged 85 years or older in a single hospital. RESULTS: Patients not undergoing operation, those with an ASA score of III or greater and those with advanced tumour stage were more likely to die within 30 days. Regression analysis showed that 30 day mortality was independently related to failure to undergo resection (odds ratio (O.R.), 10.0; 95% confidence interval [C.I.], 1.7-58.2; p=0.01) and an ASA score of III or greater (O.R. 13.0; 95% C.I., 1.4-12.6; p=0.03). All cause three and five year survival were 47% and 23% respectively for patients who are alive 30 days after diagnosis. Three and five year relative survivals were 64% and 54%, respectively. Long-term outcome was independently related to tumour stage (relative risk [R.R.], 2; 95% C.I., 1.3-3.1; p=0.001), presence of co-morbid diseases (R.R., 2.8; 95% C.I., 1.3-6.0; p=0.007) and lipid peroxidation status (R.R., 2.9; 95% C.I., 1.1-7.5; p=0.025). CONCLUSIONS: An active multidisciplinary approach to the care of patients with CRC at the upper extreme of life is reasonable. It also seems sensible to individualise care based upon the extent of disease at diagnosis and the presence of co-morbid conditions. Further studies to examine the role of lipid peroxidation are warranted.

Prognostic significance of tumor budding in rectal cancer biopsies before neoadjuvant therapy.

Tumor budding is an increasingly important prognostic feature for pathologists to recognize. The aim of this study was to correlate intra-tumoral budding in pre-treatment rectal cancer biopsies with pathological response to neoadjuvant chemoradiotherapy and with long-term outcome. Data from a prospectively maintained database were acquired from patients with locally advanced rectal cancer who underwent neoadjuvant chemoradiotherapy. Pre-treatment rectal biopsies were retrospectively reviewed for evidence of intra-tumoral budding. Multivariate logistic regression was used to identify factors contributing to cancer-specific death, expressed as hazard ratios with 95% confidence intervals. Of the 185 patients with locally advanced rectal cancer, 89 patients met the eligibility criteria, of whom 18 (20%) exhibited budding in a pre-treatment tumor biopsy. Intra-tumoral budding predicted a poor pathological response to neoadjuvant chemoradiotherapy (higher ypT stage, P=0.032; lymph node involvement, P=0.018; lymphovascular invasion, P=0.004; and residual poorly differentiated tumors, P=0.005). No patient with intra-tumoral budding exhibited a tumor regression grade 1 or complete pathological response, providing a 100% specificity and positive predictive value for non-response to neoadjuvant chemoradiotherapy. Intra-tumoral budding was associated with a lower disease-free 5-year survival rate (33 vs 78%, P<0.001), cancer-specific 5-year survival rate (61 vs 87%, P=0.021) and predicted cancer-specific death (hazard ratio 3.51, 95% confidence interval 1.03-11.93, P=0.040). Intra-tumoral budding at diagnosis of rectal cancer identifies those who will poorly respond to neoadjuvant chemoradiotherapy and those with a poor prognosis.

Depth-dependent differences in community structure of the human colonic microbiota in health.

OBJECTIVE: The aims of this study were to develop techniques for spatial microbial assessment in humans and to establish colonic luminal and mucosal spatial ecology, encompassing longitudinal and cross-sectional axes. DESIGN: A microbiological protected specimen brush was used in conjunction with a biopsy forceps to sample the colon in nine healthy volunteers undergoing colonoscopy. Terminal Restriction Fragment Length Polymorphism analysis was used to determine the major variables in the spatial organization of the colonic microbiota. RESULTS: Protected Specimen Brush sampling retrieved region-specific, uncontaminated samples that were enriched for bacterial DNA and depleted in human DNA when compared to biopsy samples. Terminal Restriction Fragment Length Polymorphism analysis revealed a segmentation of bacterial communities between the luminal brush and biopsy-associated ecological niches with little variability across the longitudinal axis of the colon and reduced diversity in brush samples. CONCLUSION: These results support the concept of a microbiota with little longitudinal variability but with some degree of segregation between luminal and mucosal communities.

The influence of CTGF single-nucleotide polymorphisms on outcomes in Crohn's disease.

OBJECTIVE: To examine the association between single-nucleotide polymorphisms (SNPs) in CTGF (connective tissue growth factor) and patient outcomes after terminal ileal resection for Crohn's disease. BACKGROUND: The primary indication for intestinal resection in Crohn's disease is fibrostenotic terminal ileal disease. CTGF is a cytokine overexpressed in the intestine of patients with Crohn's disease that influences outcomes in other disease processes. METHODS: DNA was extracted from formalin-fixed, paraffin-embedded tissue from 147 patients with Crohn's disease who had undergone terminal ileal resection between 1981 and 2009. Genotyping was performed for 4 CTGF SNPs (rs9402373, rs12526196, rs6918698, and rs9399005), which modulate nuclear factor binding and CTGF production, and a smad3 SNP (rs17293632) involved in the CTGF pathway. Patients were phenotyped using the Montreal Disease Classification. RESULTS: Sixty-seven of 147 patients (45.6%) were male; the mean age at diagnosis was 30.3 ± 12.6 years and the mean follow-up duration was 8.3 ± 7.1 years. Genotype-phenotype analysis demonstrated that the rs6918698GG genotype was associated with an older age of disease onset [>40 years; 30.6% vs 13.2%; odds ratio (OR): 2.891; 95% confidence interval (CI): 1.170-7.147). The rs9402373CC genotype was positively associated with type B1 disease (50.7% vs 26.3%; OR: 2.876; 95% CI: 1.226-6.743) and negatively associated with B2 disease (37.0% vs 65.0%; OR: 0.317; 95% CI: 0.144-0.699). None of the 5 SNPs assessed influenced clinical or surgical recurrence of Crohn's disease after intestinal resection. On multivariate analysis, male sex odds ratio (OR): 0.235; 95% CI: 0.073-0.755; P = 0.015] and never having smoked tobacco (OR: 0.249; 95% CI: 0.070-0.894; P = 0.033) reduced the risk, whereas having a prior appendectomy increased the risk (OR: 5.048; 95% CI: 1.632-15.617; P = 0.005) of surgical recurrence. CONCLUSIONS: These data implicate the rs6918698GG genotype with an age of disease onset of greater than 40 years in Crohn's disease whereas the rs9402373CC genotype is associated with a nonstricturing, nonpenetrating disease phenotype. CTGF SNPs do not influence the rate of recurrence after terminal ileal resection for Crohn's disease.

A comparative study of short- and medium-term outcomes comparing emergent surgery and stenting as a bridge to surgery in patients with acute malignant colonic obstruction.

BACKGROUND: The use of self-expanding metal stents as a bridge to surgery in the setting of malignant colorectal obstruction has been advocated as an acceptable alternative to emergency surgery. However, concerns about the safety of stenting have been raised following recent randomized studies. OBJECTIVES: The aim of the current study was to compare outcomes. DESIGN: This was an observational, comparative study. SETTINGS: This study was conducted at a tertiary referral center and university teaching hospital. PATIENTS AND INTERVENTIONS: Patients with malignant colonic obstruction (n = 49) treated by either emergency surgery (n = 26) or with stent placement (n = 23) as a bridge to surgery were identified and followed. MAIN OUTCOME MEASURES: Short-term outcomes including stoma rates and postoperative morbidity and medium-term oncological outcomes were compared based on an "intention-to-treat" analysis. RESULTS: Patients in both groups were well matched on clinicopathological parameters. Technical and clinical successful stent deployment was achieved in 91% and 83%. This did not adversely impact cancer-specific and overall survival (log rank = nonsignificant). No difference was observed in stoma rates, primary anastomosis rates, perioperative mortality rates, or reoperation rates between the 2 groups. Significantly fewer patients underwent total colectomy in the stent group in comparison with the emergency surgery group (1/23 vs 6/26: p = 0.027). There was no difference in postoperative morbidity (59% vs 66%: p = 0.09). There was a significant reduction in readmission rates in the stent group (5/26 vs 0/23: p = 0.038). LIMITATIONS: The small sample size of this study could lead to type II error. In addition, the study was nonrandomized and demonstrated a limited length of follow-up. CONCLUSION: Despite a high rate of technical and clinical success in selected patients with colonic obstruction, stenting has no impact on stoma rates. Despite concerns about the rate of stent-associated perforation, stenting does not adversely impact disease progression or survival. Future comparative trials are essential to better define the role of stenting in this setting and to ensure that we are not using costly technology to create an elective operative situation without concomitant patient benefits.

Effects of radiation on levels of DNA damage in normal non-adjacent mucosa from colorectal cancer cases.

PURPOSE: Defects in DNA repair pathways have been linked with colorectal cancer (CRC). Adjuvant radiotherapy has become commonplace in the treatment of rectal cancer however it is associated with a higher rate of second cancer formation. It is known that radiation results in DNA damage directly or indirectly by radiation-induced bystander effect (RIBE) by causing double-strand breaks (DSBs). The majority of work in RIBE has been performed in cell lines and limited studies have been in or ex vivo. METHODS: The first study aim was to examine by immunohistochemistry, levels of DSB (expression of the protein MRE11) in normal colonic tissue outside the irradiated field post neo-adjuvant radiotherapy (group 1). These levels were compared to (a) irradiated tumour tissue post neo-adjuvant radiation within the same group, (b) a CRC patient group (group 2) who had not undergone neo-adjuvant radiotherapy and (c) a non-cancer patient group (group 3). The second aim was to determine if MRE11 expression levels were related to survival or radio-sensitivity post neo-adjuvant radiotherapy. RESULTS: There was a highly significant increase in MRE 11 expression in group 1 versus groups 2 and 3 (p < 0.001). There was no association between MRE11 levels and survival or radio-sensitivity. CONCLUSION: Our findings show radiotherapy causes DSBs at significantly higher levels in normal colonic mucosa of patients post neo-adjuvant treatment which may represent RIBE. If this damage remains unrepaired, increased levels of genomic instability may contribute to the higher occurrence of second cancers in patients treated post neo-adjuvant radiotherapy.