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A recent case series of diabetic ketoacidosis (DKA) associated with colonoscopy in sodium–glucose cotransporter 2 inhibitor (SGLT2i)-treated diabetes (1) prompted a clinical alert update to include colonoscopy (2). That update advised colonoscopy cancellation when capillary ketone concentrations are >1.0 mmol/L (if blood gas analysis is unavailable) when SGLT2i have not been withheld for 72 h. However, those guidelines were formulated in the absence of data regarding the normal range for capillary ketone concentrations at the time of colonoscopy. Unnecessary colonoscopy cancellation carries risks, including delays in possible cancer detection, and psychological consequences, whereas a ketone cutoff that is too high increases the risk of DKA. To define a ketone concentration that may serve as an empirical determinant of the need for further investigation, we now report a nondiabetic reference interval for capillary ketone concentrations at the time of colonoscopy from a multicenter observational study conducted between June and December 2020 at four tertiary health services (Alfred, Austin, Eastern, and Western Health) in Melbourne, Australia. Multisite approval was granted by the Alfred Human Research Ethics Committee. Inclusion criteria for the reference population were community-dwelling, normoglycemic adults undergoing colonoscopy. Exclusion criteria were a history of diabetes, pancreatitis, pancreatic cancer, pancreatic surgery, hemochromatosis, cystic fibrosis, starvation ketosis (defined as fasting >72 h), pregnancy, or the discovery during recruitment of a fasting capillary glucose >5.5 mmol/L (100 mg/dL). Participants with type 2 diabetes were also recruited to compare capillary ketone concentrations with the reference interval population. Except for physician-adjudicated …

Background & Aims Adenoma detection rate (ADR) is an important quality assurance measure for colonoscopy. Some studies suggest that narrow-band imaging (NBI) may be more effective at detecting adenomas than white-light endoscopy (WLE) when bowel preparation is optimal. We conducted a meta-analysis of data from individual patients in randomized controlled trials that compared the efficacy of NBI to WLE in detection of adenomas. Methods We searched MEDLINE, EMBASE, and Cochrane Library databases through April 2017 for randomized controlled trials that assessed detection of colon polyps by high-definition WLE vs NBI and from which data on individual patients were available. The primary outcome measure was ADR adjusted for bowel preparation quality. Multilevel regression models were used with patients nested within trials, and trial included as a random effect. Results We collected data from 11 trials, comprising 4491 patients and 6636 polyps detected. Adenomas were detected in 952 of 2251 (42.3%) participants examined by WLE vs 1011 of 2239 (45.2%) participants examined by NBI (unadjusted odds ratio [OR] for detection of adenoma by WLE vs NBI, 1.14; 95% CI, 1.01–1.29; P = .04). NBI outperformed WLE only when bowel preparation was best: adequate preparation OR, 1.07 (95% CI, 0.92–1.24; P = .38) vs best preparation OR, 1.30 (95% CI, 1.04–1.62; P = .02). Second-generation bright NBI had a better ADR than WLE (second-generation NBI OR, 1.28; 95% CI, 1.05–1.56; P = .02), whereas first-generation NBI did not. NBI detected more non-adenomatous polyps than WLE (OR, 1.24; 95% CI, 1.06–1.44; P = .008) and flat polyps than WLE (OR, 1.24; 95% CI, 1.02–1.51; P = .03). Conclusions In a meta-analysis of data from individual patients in randomized controlled trials, we found NBI to have a higher ADR than WLE, and that this effect is greater when bowel preparation is optimal.

Background and Aim The addition of a laxative prior to a standard bowel preparation (BP) has shown variable results in efficacy, safety, and tolerability of the BP. This study compared the efficacy and tolerability of a macrogol‐augmented BP (M‐BP) with standard BP for routine colonoscopy in unselected patients. Methods Adults undergoing outpatient colonoscopy were randomized to either M‐BP (one sachet of macrogol‐based osmotic laxative (MBOL) twice daily for eight doses prior to standard preparation) or BP (split‐dose of polyethylene glycol and sodium picosulfate). Bowel cleansing was assessed using the Ottawa BP scale. Risk factors for poor BP, patient satisfaction, and tolerance were recorded. Results This randomized trial was stopped due to futility after 14 months; at that point, 92 subjects were randomized to the study arm and 102 to the control arm. M‐BP had a success rate of 71.7% (95% CI: 58.5–82.7%), while the BP had a success rate of 67.7% (95% CI: 54.9–78.8%), with a Pearson χ 2 test P‐value of 0.639, which exceeded the cut‐off for futility (0.313). In subgroup analyses, there were statistically significant decreases in the rates of successful BP in patients taking regular opioids and regular laxatives. Both preparations were well tolerated, with no difference between groups (BP – 5.3% and M‐BP – 6.6% P = 0.66). Conclusion The addition of MBOL prior to a standard BP in unselected subjects does not significantly improve bowel cleanliness at routine colonoscopy. The role of this laxative in patients at high risk of poor preparation warrants further investigation.

BACKGROUND Critical peptic ulcer bleeding requiring massive transfusion is a gastroenterological emergency. Few data exist on management and outcomes. The Australian and New Zealand Massive Transfusion Registry collects comprehensive data on adult patients receiving massive transfusion across all bleeding contexts. AIM To evaluate clinical factors, management (procedural interventions, transfusions) and outcomes after massive transfusion for critical peptic ulcer bleeding. METHOD Demographics, diagnosis, procedures, and mortality data were available for 5,482 massive transfusion cases from 23 hospitals. International Classification of Diseases-Australian modification, 10th Edition codes were used to determine peptic ulcer bleeding and the Australian Classification of Health Intervention for interventions (endoscopic, radiological, surgical). RESULTS Peptic ulcer bleeding accounted for 270 (4.9%) of all in-hospital massive transfusion cases. 70% were male. Median number of red blood cell (RBC) units transfused was 7 [interquartile-range, 6 to 10]. 30-day mortality was 19.6%. Age (75 vs 67 years; p=0.009) and Charlson Comorbidity Index (3 vs 1; p

Delayed postpolypectomy bleeding (DPPB) is the most common complication of colonoscopic polypectomy. Prophylactic clipping after an uncomplicated polypectomy is increasingly used, but it is unclear if this results in the prevention of DPPB. This study aimed to review prophylactic clip use and its effect on the rates of DPPB. MEDLINE, Embase, and the Cochran Library were systematically searched for studies (1995-March 2017) that used prophylactic hemoclips and assessed DPPB as an outcome. Of 1402 articles identified, nine papers were eligible for inclusion, evaluating 4311 patients and 7783 polyps; 118 patients experienced a DPPB, and 49 of these patients received prophylactic clips. There was no significant difference in DPPB rates in patients who received prophylactic clipping compared to those who did not (odd ratio: 0.8; 95% confidence interval: 0.36-1.77; P = 0.56). There was also no significant difference in the DPPB of polyps

Background: To help adapt cardiovascular disease risk prediction approaches to low-income and middle-income countries, WHO has convened an effort to develop, evaluate, and illustrate revised risk models. Here, we report the derivation, validation, and illustration of the revised WHO cardiovascular disease risk prediction charts that have been adapted to the circumstances of 21 global regions. Methods: In this model revision initiative, we derived 10-year risk prediction models for fatal and non-fatal cardiovascular disease (ie, myocardial infarction and stroke) using individual participant data from the Emerging Risk Factors Collaboration. Models included information on age, smoking status, systolic blood pressure, history of diabetes, and total cholesterol. For derivation, we included participants aged 40–80 years without a known baseline history of cardiovascular disease, who were followed up until the first myocardial infarction, fatal coronary heart disease, or stroke event. We recalibrated models using age-specific and sex-specific incidences and risk factor values available from 21 global regions. For external validation, we analysed individual participant data from studies distinct from those used in model derivation. We illustrated models by analysing data on a further 123 743 individuals from surveys in 79 countries collected with the WHO STEPwise Approach to Surveillance. Findings: Our risk model derivation involved 376 177 individuals from 85 cohorts, and 19 333 incident cardiovascular events recorded during 10 years of follow-up. The derived risk prediction models discriminated well in external validation cohorts (19 cohorts, 1 096 061 individuals, 25 950 cardiovascular disease events), with Harrell's C indices ranging from 0·685 (95% CI 0·629–0·741) to 0·833 (0·783–0·882). For a given risk factor profile, we found substantial variation across global regions in the estimated 10-year predicted risk. For example, estimated cardiovascular disease risk for a 60-year-old male smoker without diabetes and with systolic blood pressure of 140 mm Hg and total cholesterol of 5 mmol/L ranged from 11% in Andean Latin America to 30% in central Asia. When applied to data from 79 countries (mostly low-income and middle-income countries), the proportion of individuals aged 40–64 years estimated to be at greater than 20% risk ranged from less than 1% in Uganda to more than 16% in Egypt. Interpretation: We have derived, calibrated, and validated new WHO risk prediction models to estimate cardiovascular disease risk in 21 Global Burden of Disease regions. The widespread use of these models could enhance the accuracy, practicability, and sustainability of efforts to reduce the burden of cardiovascular disease worldwide. Funding: World Health Organization, British Heart Foundation (BHF), BHF Cambridge Centre for Research Excellence, UK Medical Research Council, and National Institute for Health Research. The WHO CVD Risk Chart Working Group, for complete list of authors see http://dx.doi.org/10.1016/S2214-109X(19)30318-3

Background Management of major gastrointestinal bleeding (GIB) may require massive transfusion (MT), but limited data are available. Upper and lower GIB have different aetiologies, prognosis, bleeding patterns and outcomes. Better understanding of current transfusion management and outcomes in these patients is important. We sought to define and validate an algorithm based on clinical coding data to distinguish critical upper and lower GIB using data from the Australian and New Zealand Massive Transfusion Registry (ANZ-MTR). Study design and methods Australian and New Zealand Massive Transfusion Registry hospital-source data on adult patients receiving a MT (defined as ≥5 red cell units within 4 h) for any bleeding context were used. An algorithm allocating ICD-10-AM codes into 'probable' or 'possible' causes of GIB was developed and applied to the ANZ-MTR. Source medical records of 69 randomly selected cases were independently reviewed to validate the algorithm. Results Of 5482 MT cases available from 25 hospitals, 716 (13%) were identified as GIB with 538/716 (75%) categorized 'probable' and 178/716 'possible' GIB. Upper and lower GIB causes of MT were identified for 455/538 (85%) and 76/538 (14%) 'probable' cases, respectively; 7/538 (1·3%) cases had both upper and lower GIB. Allocation by the algorithm into a 'probable' GIB category had a 95·7% (CI: 90-100%) positive predictive value when validated against source medical records. Conclusion An algorithm based on ICD-10-AM codes can be used to accurately categorize patients with luminal GIB as the primary reason for MT, enabling further study of this critically unwell and resource-intensive cohort of patients.

Background and Aim Cold snare polypectomy is safe and efficacious for removing polyps, Cold snare polypectomy of 10–20 mm sessile polyps is safe, and no complications were seen when compared with hot snare.

Background Patients with longstanding ulcerative colitis (UC) are at increased risk for developing CRC. During surveillance colonoscopy, a variety of dysplastic and non-dysplastic lesions are detected. The aim of this study was to address the diagnostic accuracy of endoscopic differentiation autofluorescence imaging (AFI), narrow band imaging (NBI) and chromoendoscopy (CE). Methods This is a pre-specified additional analysis of a multicentre randomised controlled trial that compared AFI with CE for dysplasia detection in 210 patients with longstanding UC (FIND-UC trial). In the AFI arm, endoscopists recorded AFI color and Kudo pit pattern using NBI. Kudo pit pattern was described in the CE arm. For AFI, purple colour and ambiguous colour combined with pit pattern type III-V on NBI was considered dysplastic. For pit pattern description using NBI and CE, type III-V was considered dysplastic. Histology was the reference standard; sessile serrated lesions without dysplasia were considered non-dysplastic. Results In total, 52 dysplastic and 255 non-dysplastic lesions were detected. Overall sensitivity for real-time prediction of dysplasia was 76.9% (95% confidence interval (CI) 46.2-95.0) for NBI and AFI combined, and 81.6% (95% CI 65.7-92.3) for CE (p=0.72). For high confidence predictions, negative predictive value (NPV) of the combination of AFI and NBI was 97.7% (95% CI 92.4-99.3) versus 97.4% (95% CI 90.2-97.2) for CE (p=0.41). Interpretation Sensitivity for endoscopic differentiation of dysplastic lesions detected during surveillance of patients with longstanding UC seems limited. The high NPV using these techniques may be sufficient to leave suspected non-dysplastic lesions in situ without biopsy (NTR4062).

Serrated polyps have been recognised in the last decade\ud as important premalignant lesions accounting for\ud between 15% and 30% of colorectal cancers. There is\ud therefore a clinical need for guidance on how to manage\ud these lesions; however, the evidence base is limited. A\ud working group was commission by the British Society of\ud Gastroenterology (BSG) Endoscopy section to review the\ud available evidence and develop a position statement to\ud provide clinical guidance until the evidence becomes\ud available to support a formal guideline. The scope of the\ud position statement was wide-ranging and included:\ud evidence that serrated lesions have premalignant\ud potential; detection and resection of serrated lesions;\ud surveillance strategies after detection of serrated lesions;\ud special situations—serrated polyposis syndrome\ud (including surgery) and serrated lesions in colitis;\ud education, audit and benchmarks and research\ud questions. Statements on these issues were proposed\ud where the evidence was deemed sufficient, and reevaluated\ud modified via a Delphi process until >80%\ud agreement was reached. The Grading of\ud Recommendations, Assessment, Development and\ud Evaluations (GRADE) tool was used to assess the\ud strength of evidence and strength of recommendation\ud for finalised statements. Key recommendation: we\ud suggest that until further evidence on the efficacy or\ud otherwise of surveillance are published, patients with\ud sessile serrated lesions (SSLs) that appear associated\ud with a higher risk of future neoplasia or colorectal\ud cancer (SSLs ≥10 mm or serrated lesions harbouring\ud dysplasia including traditional serrated adenomas)\ud should be offered a one-off colonoscopic surveillance\ud examination at 3 years (weak recommendation, low\ud quality evidence, 90% agreement).

Concurrent cardiovascular disease and antiplatelet use (clopidogrel, prasugrel and ticagrelor) use poses a significant peri-endoscopic management challenge with a paucity of high-quality evidence available. Antiplatelet temporary interruption places patients at risk of serious cardiovascular thrombotic events. Continuing these agents potentially increases the risk of procedure related bleeding however this risk could be sufficiently mitigated by cold snare polypectomy and endoscopic clipping to manage intraprocedural bleeding, making routine colonoscopy on continued antiplatelet agents safe.The EPOC trial will examine whether continuation of antiplatelet therapy (clopidogrel, prasugrel or ticagrelor) as single or dual therapy with aspirin, is inferior or superior to temporary interruption of antiplatelet therapy, current standard of care, with regard to the use of endoscopic rescue clips or clinically significant post-polypectomy bleeding after cold snare polypectomy of polyps ≤10 mm. EPOC is a parallel group, proceduralist-blinded randomized controlled trial comparing recruiting patients on antiplatelet therapy undergoing elective colonoscopy.This trial is underway throughout Australia and New Zealand with a view to expanding to additional sites. 496 subjects in each arm are required for this study. EPOC is the first randomised controlled trial comparing temporary interruption with continuation of antiplatelet therapy in patients undergoing elective colonoscopy. Keywords: Clopidogrel, Prasugrel, Ticagrelor, Antiplatelet, Thienopyridine, Colonoscopy, Polypectomy, Bleeding

Human herpesvirus-6 (HHV-6)A and 6B are ubiquitous betaherpesviruses viruses with lymphotropic and neurotropic potential. As reported earlier, these viruses establish latency by integration into the telomeres of host chromosomes. Chromosomally integrated HHV-6 (CIHHV-6) can be transmitted vertically from parent to child. Some CIHHV-6 patients are suffering from neurological symptoms, while others remain asymptomatic. Four patients with CIHHV-6 and CNS dysfunction were treated with valganciclovir or foscarnet. HHV-6 replication was detected by reverse transcriptase polymerase chain reaction amplification of a late envelope glycoprotein. In this study we also compared the inherited and persistent HHV-6 viruses by DNA sequencing. The prevalence of CIHHV-6 in this cohort of adult patients from the USA suffering from a wide range of neurological symptoms including long-term fatigue were found significantly greater than the reported 0.8% in the general population. Long-term antiviral therapy inhibited HHV-6 replication as documented by loss of viral mRNA production. Sequence comparison of the mRNA and the inherited viral genome revealed that the transcript is produced by an exogenous virus. In conclusion, the data presented here document that some individuals with CIHHV-6 are infected persistently with exogenous HHV-6 strains that lead to a wide range of neurological symptoms; the proposed name for this condition is inherited herpesvirus 6 syndrome or IHS.

Endoscopic scoring systems in Crohn's disease and ulcerative colitis aim to translate the assessment of mucosal disease activity into a quantified value. This value seeks to provide a clear, objective record of the endoscopic mucosal severity, which can then be used to guide medical management decisions. The primary driver of all endoscopic indices, however, is to define a scale of responsiveness for therapeutic endpoints in clinical trials. Mucosal healing now has widespread acceptance as a therapeutic and clinical endpoint, but despite the development of multiple endoscopic scoring systems, the endoscopic definition has yet to be resolved. This review describes recent advances in endoscopic scoring systems for ulcerative colitis (Mayo Clinic endoscopy subscore, UCEIS, and UCCIS among others) and for Crohn's disease.

Kaposi's sarcoma-associated herpesvirus (KSHV) is the causative agent of Kaposi's sarcoma and B-lymphocyte disorders, primary effusion lymphoma (PEL) and Multicentric Castleman's disease (MCD). KSHV usually exists in a latent form in which the viral genome is circularized into an extrachormosomal episome. However, induction of lytic replication by environmental stimuli or chemical agents is important for the spread of KSHV. The switch between latency and lytic replication is regulated by epigenetic factors. Hypomethylation of the promother of replication and transcription activator (RTA), which is essential for the lytic switch, leads to KSHV reactivation. Histone acetylation induces KSHV replication by influencing protein-protein-associations and transcription factor binding. Histone modifications also determine chromatin structure and nucleosome positioning, which are important for KSHV DNA replication during latency. The association of KSHV proteins with chromatin remodeling complexes promotes the open chromatin structure needed for transcription factor binding and DNA replication. Additionally, post-translational modification of KSHV proteins is important for the regulation of RTA activity and KSHV replication. KSHV may also cause epigenetic modification of the host genome, contributing to promoter hypermethylation of tumor suppressor genes in KSHV-associated neoplasias.

This thesis is an investigation of chantries and their founders in fifteenth and sixteenth century Aberdeen. For the purpose of this thesis, one hundred and twenty-two chantry certificates and anniversary foundations as well as gifts to the altars were examined, encompassing a total of thirty altars at the parish church of Saint Nicholas in Aberdeen, Scotland. When this information was examined, it was discovered that the average chantry founder of Saint Nicholas was a male burgess of Aberdeen who had endowed the chantry by himself while still living. He would have given rents totalling just over £5 to a named altar, with the rents coming from a collection of plots of land in the surrounding areas. As well, the majority of the chantry and obit foundations occurred between 1430 and 1549 with peak points from 1500 to 1509, and 1520 to 1529. As conduits through which the living and the dead could interact, chantries performed a number of functions. They gave mourners a purpose after a friend or loved one had died, served as a memorial for those who feared being forgotten after death, and helped the poor by giving them a place where they were needed. As well, chantries gave the laity the ability to further participate in the everyday functions of the church. Serving to connect the different aspects of community in Aberdeen, living and dead, and lay and religious, chantries were an important part of late medieval society.