The relationship between systemic inflammatory response, screen detection and outcome in colorectal cancer.

AIM: A raised systemic inflammatory response correlates with poorer colorectal cancer (CRC) outcomes. Faecal immunochemical test bowel screening aims to detect early-stage disease. We assessed the relationship between systemic inflammatory response, screen detection and CRC survival. METHOD: A retrospective, observational cohort study compared screen-detected and non-screen-detected CRC patients undergoing resection. Systemic inflammatory response was measured using lymphocyte/monocyte, neutrophil/lymphocyte and platelet/lymphocyte ratios (LMR, NLR, PLR). Covariables were compared using χ2 testing and survival with Cox regression. RESULTS: A total of 761 patients were included (326 screen-detected, 435 non-screen-detected). Screen-detected patients had lower systemic inflammatory response: low (<2.4) LMR (28.8% vs. 44.6%; P < 0.001), moderate (3-5) or high (>5) NLR (26.1% vs. 30.6%, P < 0.001; and 7.7% vs. 19.5%, P < 0.001) and high (>150) PLR (47.2% vs. 64.6%; P < 0.001). Median follow-up was 63 months. On univariate analysis, non-screen detection (hazard ratio [HR] 2.346, 95% CI 1.687-3.261; P < 0.001), advanced TNM (P < 0.001), low LMR (HR 2.038, 95% CI 1.514-2.742; P < 0.001), moderate NLR (HR 1.588, 95% CI 1.128-2.235; P = 0.008), high NLR (HR 2.382, 95% CI 1.626-3.491; P < 0.001) and high PLR (HR 1.827, 95% CI 1.326-2.519; P < 0.001) predicted poorer overall survival (OS). Non-screen detection (HR 2.713, 95% CI 1.742-4.226; P < 0.001), TNM (P < 0.001), low LMR (HR 1.969, 95% CI 1.340-2.893; P < 0.001), high NLR (HR 2.368, 95% CI 1.448-3.875; P < 0.001) and high PLR (HR 2.110, 95% CI 1.374-3.240; P < 0.001) predicted poorer cancer-specific survival (CSS). On multivariate analysis, non-screen detection (HR 1.698, 95% CI 1.152-2.503; P = 0.008) and low LMR (HR 1.610, 95% CI 1.158-2.238; P = 0.005) independently predicted poorer OS. Non-screen detection (HR 1.847, 95% CI 1.144-2.983; P = 0.012) and high PLR (HR 1.578, 95% CI 1.018-2.444; P = 0.041) predicted poorer CSS. CONCLUSION: Screen-detected CRC patients have a lower systemic inflammatory response. Non-screen detection and systemic inflammatory response (measured by LMR and PLR respectively) were independent predictors of poorer OS and CSS.

Management of malignant T1 colorectal cancer polyps: results from a 10-year prospective observational study.

AIM: The recurrence risk associated with residual malignant cells (bowel wall/regional nodes) following T1 colorectal cancer (CRC) polypectomy must be weighed against operative morbidity. Our aim was to describe the management and outcomes of a large prospective cohort of T1 CRCs. METHOD: All T1 CRCs diagnosed between March 2007 and March 2017 at the Glasgow Royal Infirmary were included. Patients were grouped by polypectomy, rectal local excision and formal resection status. χ2 testing, multivariate binary logistic and Cox regression were performed. RESULTS: Of 236 patients, 90 (38.1%) underwent polypectomy only, six (2.6%) polypectomy and then rectal excision, 57 (24.2%) polypectomy and then resection, 14 (5.9%) rectal excision only and 69 (29.2%) primary resection. Polypectomy only correlated with male sex (P = 0.028), older age (P < 0.001), distal CRCs (P < 0.001) and pedunculated polyps (P < 0.001); primary resection with larger polyps (P < 0.001); polypectomy then resection with piecemeal excision (P = 0.002) and involved polypectomy margin (P < 0.001). Poor differentiation (OR 7.860, 95% CI 1.117-55.328; P = 0.038) independently predicted lymph node involvement. Submucosal venous invasion (hazard ratio [HR] 10.154, 95% CI 2.087-49.396; P = 0.004) and mucinous subtype (HR 7.779, 95% CI 1.566-38.625; P = 0.012) independently predicted recurrence. Submucosal venous invasion (HR 5.792, 95% CI 1.056-31.754; P = 0.043) predicted CRC-specific survival. Although 64.4% of polypectomy-only patients had margin involvement/other risk factors, none developed recurrence. Of 94 with polypectomy margin involvement, five (5.3%) had confirmed residual tumour. Overall, lymph node metastases (7.1%), recurrence (4.2%) and cancer-specific mortality (3.0%) were rare. Cancer-specific 5-year survival was high: polypectomy only (100%), polypectomy and then resection (98.2%), primary resection (100%). CONCLUSION: Surveillance may be safe for more T1 CRC polyp patients. Multidisciplinary team discussion and informed patient choice are critical.

Risk stratification for the detection of metachronous polyps after bowel screening polypectomy: clinical outcomes from the Integrated Technologies for Improved Polyp Surveillance (INCISE) study cohort.

BACKGROUND: After colorectal polypectomy, 20-50 per cent of patients develop metachronous polyps and some have increased colorectal cancer risk. British Society of Gastroenterology (BSG) 2020 guidelines recommend surveillance colonoscopy for high-risk patients based on index pathology. The aim of this study was to evaluate metachronous lesion outcome using BSG 2020 criteria. METHODS: A retrospective, multicentred study was conducted including patients who had polypectomy during screening colonoscopy (2009-2016) followed by surveillance. Demographics, index pathology, and BSG 2020 risk criteria were compared with regard to metachronous lesion pathology (non-advanced versus advanced lesions) and timing of detection (early versus late). Advanced lesions were defined as adenomas/serrated polyps greater than or equal to 10 mm, high-grade dysplasia, serrated polyps with dysplasia, or colorectal cancer, and late lesions those detected greater than 2 years after the index procedure. RESULTS: Of 3090 eligible patients, 2643 were included. Among these, retrospective BSG 2020 application would have excluded 51.5 per cent from surveillance. After a median of 36 months, the advanced polyp/colorectal cancer rate in BSG 2020 high-risk patients was 16.3 versus 13.0 per cent in low-risk patients. Older age (P = 0.008) correlated with advanced metachronous lesions. Male sex, greater than five polyps, and BSG 2020 high-risk criteria correlated with non-advanced and advanced lesions (P < 0.001). Older age (P < 0.001), villous features (P = 0.006), advanced index polyp (P = 0.020), and greater than five polyps (P < 0.001) correlated with early metachronous lesions. Male sex and BSG 2020 high-risk criteria correlated with early and late lesions (P < 0.001). On multivariable regression, increased polyp number (odds ratio (OR) 1.15 (95 per cent c.i. 1.07 to 1.25); P < 0.001) and villous features (OR 1.49 (95 per cent c.i. 1.05 to 2.10); P = 0.025) independently correlated with early advanced lesions. The rate of non-advanced and advanced metachronous polyps was higher in BSG 2020 high- versus low-risk patients (44.4 versus 35.4 per cent for non-advanced and 15.7 versus 11.8 per cent for advanced; P < 0.001), but the colorectal cancer rate was similar (0.6 versus 1.2 per cent). However, when examining only lesions detected greater than 2 years after the index colonoscopy in high- versus low-risk patients, no significant differences were observed (P = 0.140). CONCLUSION: BSG 2020 criteria correlated with metachronous polyps, but did not differentiate advanced and non-advanced lesions and were not predictive of late lesions.

The environmental impact of community caries prevention - part 1: fluoride varnish application.

Background Healthcare is a significant contributor to climate change and planetary health. Prevention of oral disease, such as caries, is an important part of any mechanism to improve sustainability. Caries prevention includes community schemes such as water fluoridation, toothbrushing, or fluoride varnish (FV) application. The aim of this study was to quantify the environmental impact of FV application.Materials and methods A comparative life cycle assessment (LCA) was conducted to quantify the environmental impact of a five-year-old child receiving two FV applications in a one-year period in schools and in dental practice.Results FV application in dental practice during an existing appointment had the lowest environmental impact in all 16 categories, followed by FV application in schools. FV application at a separate dental practice appointment had the highest impact in all categories, with a majority of the impact resulting from the patient travel into dental practice.Discussion FV application while a child is already attending dental practice (for example, at routine recall) is the most sustainable way to deliver FV. School FV programmes are an alternative, equitable way to reach all children who may not access routine care in dental practice.

The environmental impact of community caries prevention - part 2: toothbrushing programmes.

Introduction Community-level caries prevention programmes includes supervised toothbrushing in schools and the provision of toothbrushes and toothpaste. The environmental impact of these interventions is an important factor to consider when commissioning these services.Materials and methods A comparative life cycle assessment (LCA) was conducted to quantify the environmental impact of a five-year-old child receiving one of two toothbrushing programmes over a one-year period; supervised toothbrushing in school, or the provision of toothbrushes and toothpaste.Results Supervised toothbrushing had a lower environmental impact than provision of toothbrushes and toothpaste in all 16 impact categories measured. The water use needed for children to brush their teeth was the greatest contributing factor to the provision of toothbrushes and toothpaste, accounting for an average of 48.65% of the impact results.Discussion All community-level caries prevention programmes have an associated environmental cost. LCA is one way to quantify the environmental impact of healthcare services and can be used along with cost and clinical effectives data to inform public healthcare policy. Organisations responsible for these programmes could use the results of this study to consider ways to reduce the environmental impact of their services.

The planetary health effects of COVID-19 in dental care: a life cycle assessment approach.

Aims COVID-19 has significantly impacted the safety guidelines for personal protective equipment (PPE) within dental services. We quantified and compared the environmental impact of different forms of PPE.Methods The PPE items were divided into three categories: 1) the body protection category, which included disposable and reusable gowns; 2) the eye protection category, which included a visor with a disposable face shield and a reusable visor; and 3) the respiratory protection category, which included respirator FP2SLw, respirator FFP2 and surgical masks. The OpenLCA software was used for analysing and comparing the environmental impact of all PPE products in the three categories.Results The life cycle assessment results of this study showed that damage to human health was more significant for the reusable gown than the disposable gown for the body-protection-category PPE. A visor with a disposable face shield had a higher environmental footprint than the reusable visor across all impact categories for the eye protection category. In addition, a visor with a disposable face shield released five times more carbon dioxide equivalent emissions and used four times more dissipated water and three times more fossil fuels than the reusable visor. A disposable gown used four times more dissipated water and three times more fossil fuels than reusable gowns. For respiratory PPE, the FP2SLw respirator had the highest burden in all 16 categories, followed by the FFP2 respirator and then the surgical mask.Conclusion The environmental impact of PPE is notable and could be reduced through using less damaging domestic products and increased usage of reusables. In addition, the selection of PPE that are reusable and made of recyclable materials can help to minimise the environmental impact and reduce environmental resource depletion.

A review of HTM 01-05 through an environmentally sustainable lens.

Patients deserve to be treated in a safe and clean environment with consistent standards of care every time they receive treatment. It is essential that the risk of person-to-person transmission of infections be minimised, yet it is also essential that planetary harm (and therefore public harm) is minimised with respect to resource consumption, air pollution, environmental degradation etc.In 2013, the Department of Health introduced the Health Technical Memorandum (HTM) 01-05 providing dental practices with advice on patient safety when decontaminating reusable instruments in primary care. This paper provides a commentary on HTM 01-05 and similar decontamination guidance. We believe all decontamination documents needs to reflect the so-called 'triple bottom line' - the finance, social cost and impact on the planet.The authors provide an environmental commentary on a number of items mentioned in decontamination documents, including autoclaves (including the use of helix tests), disposable paper towels, undertaking hand hygiene, using a log book, plastic bag use, the use of personal protective equipment, remote decontamination units, single use instruments, single use wipes, disinfection chemicals (for example, sodium hypochlorite) thermal disinfection and wrapping of instruments.It is hoped, in the spirit of the ever-increasing numbers of papers published to highlight how healthcare (and dentistry) could become more sustainable, that these critiques will be taken in the spirit of providing a beginning of further discussion from an environmental perspective.

Prevalence of repeat faecal immunochemical testing in symptomatic patients attending primary care.

AIM: The faecal immunochemical test (FIT) for faecal haemoglobin (f-Hb) helps determine the risk of colorectal cancer (CRC) and has been integrated into symptomatic referral pathways. 'Safety netting' advice includes considering referral for persistent symptoms, but no published data exists on repeated FITs. We aimed to examine the prevalence of serial FITs in primary care and CRC risk in these patients. METHOD: A multicentre, retrospective, observational study was conducted of patients with two or more consecutive f-Hb results within a year from three Scottish Health Boards which utilize FIT in primary care. Cancer registry data ensured identification of CRC cases. RESULTS: Overall, 135 396 FIT results were reviewed, of which 12 359 were serial results reported within 12 months (9.1%), derived from 5761 patients. Of these, 42 (0.7%) were diagnosed with CRC. A total of 3487 (60.5%) patients had two f-Hb < 10 µg/g, 944 (16.4%) had f-Hb ≥ 10 µg/g followed by <10 µg/g, 704 (12.2%) f-Hb < 10 µg/g followed by ≥10 µg/g and 626 (10.9%) had two f-Hb ≥ 10 µg/g. The CRC rate in each group was 0.1%, 0.4%, 1.4% and 4.0%, respectively. Seven hundred and thirty four patients submitted more than two FITs within a year. The likelihood of one or more f-Hb ≥ 10 µg/g rose from 40.4% with two samples to 100% with six, while the CRC rate fell from 0.8% to 0%. CONCLUSION: Serial FITs within a year account for 9.1% of all results in our Boards. CRC prevalence amongst symptomatic patients with serial FIT is lower than in single-FIT cohorts. Performing two FITs within a year for patients with persistent symptoms effectively acts as a safety net, while performing more than two within this timeframe is unlikely to be beneficial.

Photoresponsive Small Molecule Inhibitors for the Remote Control of Enzyme Activity.

The development of new and effective therapeutics is reliant on the ability to study the underlying mechanisms of potential drug targets in live cells and multicellular systems. A persistent challenge in many drug development programmes is poor selectivity, which can obscure the mechanisms involved and lead to poorly understood modes of action. In efforts to improve our understanding of these complex processes, small molecule inhibitors have been developed in which their OFF/ON therapeutic activity can be toggled using light. Photopharmacology is devoted to using light to modulate drugs. Herein, we highlight the recent progress made towards the development of light-responsive small molecule inhibitors of selected enzymatic targets. Given the size of this field, literature from 2015 onwards has been reviewed.

Alternative diagnoses and demographics associated with a raised quantitative faecal immunochemical test in symptomatic patients.

BACKGROUND: The faecal immunochemical test (FIT) has proven utility for colorectal cancer detection in symptomatic patients. However, most patients with a raised faecal haemoglobin (f-Hb) do not have colorectal cancer. We investigated alternative diagnoses and demographics associated with a raised f-Hb in symptomatic patients. METHODS: A retrospective, observational study was performed of patients with FIT submitted between August 2018 to January 2019 in NHS Greater Glasgow and Clyde followed by colonoscopy. Colonoscopy/pathology reports were searched for alternative diagnoses. Covariables were compared using the χ2 test. Multivariate binary logistic regression identified independent predictors of a raised f-Hb. RESULTS: 1272 patients were included. In addition to colorectal cancer (odds ratio (OR), 9.27 (95% confidence interval (CI): 3.61-23.83; p < 0.001)), older age (OR, 1.52 (95% CI: 1.00-2.32; p = 0.05)), deprivation (OR, 1.54 (95% CI: 1.21-1.94; p < 0.001)), oral anticoagulants (OR, 1.78 (95% CI: 1.01-3.15; p = 0.046)), rectal bleeding (OR, 1.47 (95% CI: 1.15-1.88; p = 0.002)), advanced adenoma (OR, 7.52 (95% CI: 3.90-14.49; p < 0.001)), non-advanced polyps (OR, 1.78 (95% CI: 1.33-2.38; p < 0.001)) and inflammatory bowel disease (IBD) (OR, 4.19 (95% CI: 2.17-8.07; p < 0.001)) independently predicted raised f-Hb. Deprivation (Scottish Index of Multiple Deprivation (SIMD) 1-2: OR, 2.13 (95% CI: 1.38-3.29; p = 0.001)) independently predicted a raised f-Hb in patients with no pathology found at colonoscopy. CONCLUSIONS: An elevated f-Hb is independently associated with older age, deprivation, anticoagulants, rectal bleeding, advanced adenoma, non-advanced polyps and IBD in symptomatic patients. Deprivation is associated with a raised f-Hb in the absence of pathology. This must be considered when utilising FIT in symptomatic patients.

Combining the quantitative faecal immunochemical test and full blood count reliably rules out colorectal cancer in a symptomatic patient referral pathway.

PURPOSE: Faecal Immunochemical Test (FIT) has proven utility for Colorectal Cancer (CRC) detection in symptomatic patients. Most studies have examined FIT in symptomatic patients subsequently referred from primary care. We investigated associations between CRC and FIT in both referred and non-referred symptomatic patients. METHODS: A retrospective, observational study of all patients with a FIT submitted Aug 2018 to Jan 2019 in NHS GG&C was performed. Referral to colorectal/gastroenterology and decision to perform colonoscopy were recorded. FIT results were grouped as f-Hb < 10/10-149/150-399/ ≥ 400 µg/g. The MCN cancer registry identified new cases of CRC. Covariables were compared using the χ2 test. Multivariate binary logistic regression identified independent predictors of CRC. RESULTS: A total of 4968 patients were included. Raised FIT correlated with decision to refer (p < 0.001) and scope (p < 0.001). With 23-month median follow-up, 61 patients were diagnosed with CRC. These patients were older (median 69 vs 59 years, cancer and no cancer respectively, p = 0.001), more likely to be male (55.7% vs 42.1%, p = 0.033), and to report rectal bleeding (51.7% vs 36.1%, p = 0.013). FIT (< 10 µg/g 8.2% vs 76.7% and ≥ 400 µg/g 55.7% vs 3.8%, p < 0.001) and anaemia (45.9% vs 19.7%, p < 0.001) were associated with CRC. On multivariate analysis, age (p = 0.023), male sex (p = 0.04), FIT (≥ 400 OR 54.256 (95% CI:20.683-142.325; p < 0.001)), and anaemia (OR 1.956 (1.071-3.574; p = 0.029)) independently predicted CRC. One patient (0.04%) with a negative FIT and normal haemoglobin had CRC. CONCLUSION: GP referral and secondary care investigation patterns were influenced by FIT. The combination of normal Hb and f-Hb excluded CRC in 99.96% of cases, providing excellent reassurance to those prioritising access to endoscopy services.

Novel Methods of Risk Stratifying Patients for Metachronous, Pre-Malignant Colorectal Polyps: A Systematic Review.

INTRODUCTION: Despite conventional measures of future polyp risk (histology, dysplasia, size, number), surveillance places a burden on patients and colonoscopy services. We aimed to review novel risk stratification techniques. METHODS: A systematic literature review was performed for studies using genomics, transcriptomics, IHC or microbiome as markers of metachronous polyp risk. RESULTS: 4165 papers underwent title, 303 abstract and 215 full paper review. 25 papers were included. 49 mutations/ SNPs/ haplotypes in 23 genes/ chromosomal regions (KRAS, APC, EGFR, COX1/2, IL23R, DRD2, CYP2C9/24A1/7A1, UGT1A6, ODC, ALOX12/15, PGDH, SRC, IGSF5, KCNS3, EPHB1/ KY, FAM188b, 3p24.1, 9q33.2, 13q33.2) correlated with metachronous adenoma / advanced adenoma risk. Expression levels of 6 proteins correlated with metachronous adenoma (p53, ß-catenin, COX2, Adnab-9, ALDH1A1) or sessile serrated polyp (ANXA10) risk. CONCLUSION: Although genomic and IHC markers correlated with metachronous polyp risk, it seems likely that a panel of novel markers will be required to refine this risk.

The Relationship Between Co-morbidity, Screen-Detection and Outcome in Patients Undergoing Resection for Colorectal Cancer.

BACKGROUND: Bowel cancer screening increases early stage disease detection and reduces cancer-specific mortality. We assessed the relationship between co-morbidity, screen-detection and survival in colorectal cancer. METHODS: A retrospective, observational cohort study compared screen-detected (SD) and non-screen-detected (NSD) patients undergoing potentially curative resection (April 2009-March 2011). Co-morbidity was quantified using ASA, Lee and Charlson Indices. Systemic inflammatory response was measured using the neutrophil lymphocyte ratio (NLR). Covariables were compared using crosstabulation and the χ2 test for linear trend. Survival was analysed using Cox Regression. RESULTS: Of 770 patients, 331 had SD- and 439 NSD-disease. A lower proportion of SD patients had a high ASA (≥3) compared to NSD (27.2% vs 37.3%; p = 0.007). There was no significant difference in the proportion of patients with a high (≥2) Lee Index (16.3% SD vs 21.9% NSD; p = 0.054) or high (≥3) Charlson Index (22.7% SD vs 26.9% NSD; p = 0.181). On univariate analysis, NSD (HR 2.182 (1.594-2.989;p < 0.001)), emergency presentation (HR 3.390 (2.401-4.788; p < 0.001)), advanced UICC-TNM (III or IV) (p < 0.001), high ASA (≥3) (HR 1.857 (1.362-2.532; p < 0.001)), high Charlson Index (≥3) (HR 1.800 (1.333-2.432; p < 0.001)) and high (≥3) NLR (HR 1.825 (1.363-2.442; p < 0.001)) were associated with poorer overall survival (OS). NSD predicted poorer cancer-specific survival (CSS) (HR 2.763 (1.776-4.298; p < 0.001)). On multivariate analysis, NSD retained significance as an independent predictor of poorer OS (HR 1.796 (1.224-2.635; p = 0.003)) and CSS (HR 1.924 (1.193-3.102; p = 0.007)). CONCLUSIONS: Patients with SD cancers have significantly lower ASA scores. After adjusting for ASA, co-morbidity and a broad range of covariables, SD patients retain significantly better OS and CSS.

Covalent incorporation of diphenylanthracene in oxotriphenylhexanoate organogels as a quasi-solid photon upconversion matrix.

Triplet-triplet annihilation photon upconversion (TTA-UC) in solid state assemblies are desirable since they can be easily incorporated into devices such as solar cells, thus utilizing more of the solar spectrum. Realizing this is, however, a significant challenge that must circumvent the need for molecular diffusion, poor exciton migration, and detrimental back energy transfer among other hurdles. Here, we show that the above-mentioned issues can be overcome using the versatile and easily synthesized oxotriphenylhexanoate (OTHO) gelator that allows covalent incorporation of chromophores (or other functional units) at well-defined positions. To study the self-assembly properties as well as its use as a TTA-UC platform, we combine the benchmark couple platinum octaethylporphyrin as a sensitizer and 9,10-diphenylanthracene (DPA) as an annihilator, where DPA is covalently linked to the OTHO gelator at different positions. We show that TTA-UC can be achieved in the chromophore-decorated gels and that the position of attachment affects the photophysical properties as well as triplet energy transfer and triplet-triplet annihilation. This study not only provides proof-of-principle for the covalent approach but also highlights the need for a detailed mechanistic insight into the photophysical processes underpinning solid state TTA-UC.

Multi-color emission with orthogonal input triggers from a diarylethene pyrene-OTHO organogelator cocktail.

We report on a pyrene-decorated supramolecular gelator based on an oxotriphenylhexanoate (OTHO) that can switch emission profiles between the solution and gel phase. A cocktail of the gelator and a photochromic diarylethene derivative enables four distinct emissive states to be obtained, which are modulated with light and heat as orthogonal input triggers.

Normocytic anaemia is associated with systemic inflammation and poorer survival in patients with colorectal cancer treated with curative intent.

BACKGROUND: The present study aimed to characterise the prevalence and prognostic impact of normocytic anaemia in patients undergoing curative treatment for colorectal cancer. METHODS: All individuals invited to the first round of bowel cancer screening, diagnosed with colorectal cancer and treated with curative intent from April 2009 to March 2011 in a single health board were included. The modified Glasgow prognostic score (mGPS) was used to quantify preoperative systemic inflammation. Patients were grouped as having microcytic anaemia (Hb < 130 mg/L males, < 120 mg/L females and MCV < 80 fL), normocytic anaemia (Hb < 130 mg/L males, < 120 mg/L females and MCV 80-100 fL), or neither. RESULTS: Of 395,097 patients invited to screening during the study period, 872 were diagnosed with colorectal cancer. Seven hundred seventy-seven patients had FBC measured at diagnosis, of which 78 (10%) had microcytic anaemia, and 180 (23%) normocytic anaemia. On multivariate binary logistic regression, microcytic anaemia was associated with T stage (OR 1.92, 95% CI 1.26-2.91, p = 0.002) and mGPS (OR 1.57, 95% CI 1.10-2.24, p = 0.013), while normocytic anaemia was associated with colonic tumours (OR = 2.51, 95% CI 1.10-4.01, p = 0.025), T stage (OR 1.38, 95% CI 1.05-1.81, p = 0.022), and mGPS (OR 1.52, 95% CI 1.12-2.05, p = 0.007). On univariate Cox regression, there was no significant association between microcytic anaemia and cancer specific survival (CSS) (p = 0.969). Normocytic anaemia was significantly associated with poorer CSS (HR 1.55, 95% CI 1.13-2.12, p = 0.007). CONCLUSIONS: Normocytic anaemia was associated with systemic inflammation and poorer CSS. Inflammation may drive both anaemia and disease recurrence in these patients, and targeting this process may improve both.

Vertical Rectus Abdominis Myocutaneous Versus Alternative Flaps for Perineal Repair After Abdominoperineal Excision of the Rectum in the Era of Laparoscopic Surgery.

AIMS: Plastic surgical reconstruction of the perineum is often required after abdominoperineal excision of the rectum. Options for this reconstruction include a vertical rectus abdominis myocutaneous (VRAM) flap, gluteal fasciocutaneous flap, and gracilis myocutaneous flap. Although the VRAM flap is well established at most centers, less experience exists with the gluteal and gracilis flaps. In the era of laparoscopic colorectal resection, plastic surgeons are being forced to use gluteal and gracilis flaps because the VRAM flap must be tunnelled intra-abdominally requiring laparotomy. We therefore aimed to systematically review the evidence comparing VRAM, gluteal, and gracilis flaps. METHODS: A comprehensive, structured literature search was conducted using Medline, Google Scholar, and Science Direct. Studies included were randomized control trials and observational studies documenting complication rates associated with the VRAM, gluteal, or gracilis flap. RESULTS: Eleven studies meeting all inclusion and exclusion criteria were identified. When meta-analyzed, the overall rate of any perineal wound or flap complication among VRAM patients (35.8%) was significantly lower than gluteal flap (43.7%) and gracilis flap patients (52.9%) (P = 0.041). CONCLUSIONS: The VRAM flap is well established for perineal reconstruction, and this study suggests that it may be superior to the gluteal and gracilis flaps in terms perineal wound and flap complication rates. This should be taken into account when weighing up the risks and benefits of a laparoscopic approach to abdominoperineal excision of the rectum. Large studies making direct comparisons between the flap options should be conducted.

Analysis of lesion localisation at colonoscopy: outcomes from a multi-centre U.K. study.

BACKGROUND: Colonoscopy is currently the gold standard for detection of colorectal lesions, but may be limited in anatomically localising lesions. This audit aimed to determine the accuracy of colonoscopy lesion localisation, any subsequent changes in surgical management and any potentially influencing factors. METHODS: Patients undergoing colonoscopy prior to elective curative surgery for colorectal lesion/s were included from 8 registered U.K. sites (2012-2014). Three sets of data were recorded: patient factors (age, sex, BMI, screener vs. symptomatic, previous abdominal surgery); colonoscopy factors (caecal intubation, scope guide used, colonoscopist accreditation) and imaging modality. Lesion localisation was standardised with intra-operative location taken as the gold standard. Changes to surgical management were recorded. RESULTS: 364 cases were included; majority of lesions were colonic, solitary, malignant and in symptomatic referrals. 82% patients had their lesion/s correctly located at colonoscopy. Pre-operative CT visualised lesion/s in only 73% of cases with a reduction in screening patients (64 vs. 77%; p = 0.008). 5.2% incorrectly located cases at colonoscopy underwent altered surgical management, including conversion to open. Univariate analysis found colonoscopy accreditation, scope guide use, incomplete colonoscopy and previous abdominal surgery significantly influenced lesion localisation. On multi-variate analysis, caecal intubation and scope guide use remained significant (HR 0.35, 0.20-0.60 95% CI and 0.47; 0.25-0.88, respectively). CONCLUSION: Lesion localisation at colonoscopy is incorrect in 18% of cases leading to potentially significant surgical management alterations. As part of accreditation, colonoscopists need lesion localisation training and awareness of when inaccuracies can occur.

Interpenetrated Cage Structures.

This Review covers design strategies, synthetic challenges, host-guest chemistry, and functional properties of interlocked supramolecular cages. Some dynamic covalent organic structures are discussed, as are selected examples of interpenetration in metal-organic frameworks, but the main focus is on discrete coordination architectures, that is, metal-mediated dimers. Factors leading to interpenetration, such as geometry, flexibility and chemical makeup of the ligands, coordination environment, solvent effects, and selection of suitable counter anions and guest molecules, are discussed. In particular, banana-shaped bis-pyridyl ligands together with square-planar metal cations have proven to be suitable building blocks for the construction of interpenetrated double-cages obeying the formula [M4 L8 ]. The peculiar topology of these double-cages results in a linear arrangement of three mechanically coupled pockets. This allows for the implementation of interesting guest encapsulation effects such as allosteric binding and template-controlled selectivity. In stimuli-responsive systems, anionic triggers can toggle the binding of neutral guests or even induce complete structural conversions. The increasing structural and functional complexity in this class of self-assembled hosts promises the construction of intelligent receptors, novel catalytic systems, and functional materials.

Recall and understanding of risk in endodontics: A questionnaire survey.

The aim of this study was to determine the factors affecting the quantity and quality of information recalled by patients following endodontic consultations and their effect on anxiety. New patients attending the Royal Dental Hospital of Melbourne and University of Melbourne Dental Clinic were asked to complete a questionnaire assessing the amount of information retained following their consultation, determining a patient's threshold for information disclosure and the effect of the consultation on patient anxiety. Only 9% of patients recalled more than two complications. Males (P = 0.02), patients older than 65 years (P < 0.001), and patients with education limited to high school (P < 0.001) recalled significantly less information. Most respondents (71.3%) wanted information about complications with a prevalence of less than 1%. Only 11 patients (8%) developed more anxiety as a consequence of the consultation. Patients had overall poor recall of complications following endodontic consultations.