A Cell-free DNA Blood-Based Test for Colorectal Cancer Screening.

BACKGROUND: Colorectal cancer is the third most diagnosed cancer in adults in the United States. Early detection could prevent more than 90% of colorectal cancer-related deaths, yet more than one third of the screening-eligible population is not up to date with screening despite multiple available tests. A blood-based test has the potential to improve screening adherence, detect colorectal cancer earlier, and reduce colorectal cancer-related mortality. METHODS: We assessed the performance characteristics of a cell-free DNA (cfDNA) blood-based test in a population eligible for colorectal cancer screening. The coprimary outcomes were sensitivity for colorectal cancer and specificity for advanced neoplasia (colorectal cancer or advanced precancerous lesions) relative to screening colonoscopy. The secondary outcome was sensitivity to detect advanced precancerous lesions. RESULTS: The clinical validation cohort included 10,258 persons, 7861 of whom met eligibility criteria and were evaluable. A total of 83.1% of the participants with colorectal cancer detected by colonoscopy had a positive cfDNA test and 16.9% had a negative test, which indicates a sensitivity of the cfDNA test for detection of colorectal cancer of 83.1% (95% confidence interval [CI], 72.2 to 90.3). Sensitivity for stage I, II, or III colorectal cancer was 87.5% (95% CI, 75.3 to 94.1), and sensitivity for advanced precancerous lesions was 13.2% (95% CI, 11.3 to 15.3). A total of 89.6% of the participants without any advanced colorectal neoplasia (colorectal cancer or advanced precancerous lesions) identified on colonoscopy had a negative cfDNA blood-based test, whereas 10.4% had a positive cfDNA blood-based test, which indicates a specificity for any advanced neoplasia of 89.6% (95% CI, 88.8 to 90.3). Specificity for negative colonoscopy (no colorectal cancer, advanced precancerous lesions, or nonadvanced precancerous lesions) was 89.9% (95% CI, 89.0 to 90.7). CONCLUSIONS: In an average-risk screening population, this cfDNA blood-based test had 83% sensitivity for colorectal cancer, 90% specificity for advanced neoplasia, and 13% sensitivity for advanced precancerous lesions. (Funded by Guardant Health; ECLIPSE ClinicalTrials.gov number, NCT04136002.).

Province-Wide Ascertainment of Lynch Syndrome in Manitoba.

BACKGROUND & AIMS: We describe the experience of Lynch syndrome (LS) diagnosis in the province of Manitoba, Canada, over the past 20 years. METHODS: We performed a retrospective review of charts from the provincial Genetics Clinic from January 1, 2000, to May 31, 2023. We extracted data on individuals identified to carry a germline pathogenic or likely pathogenic LS gene variant, the mode of ascertainment, family history, and cascade genetic testing (CGT). Data were stratified and compared before and after the year of implementation (October 2013) of the provincial LS screening program (LSSP) and ascertainment by the LSSP vs clinic referrals (CRs). RESULTS: Between 2014 and 2021, 50 of 101 (49.5%) index cases were identified by the LSSP compared with 51 of 101 (50.5%) from CRs. The proportion of PMS2 variants was 34% (17 of 50) for LSSP index cases compared with 21.6% (11 of 51) for CRs from 2014 to 2021 (P < .001). Among CRs from 2014 to 2021, 24 of 51 (47.1%) families met the Amsterdam criteria, compared with 11 of 50 (22.0%) for the LSSP (P = .01). CGT occurred among 46.8% (95 of 203; average, 1.9 relatives/index) of first-degree relatives of CR index cases vs 36.5% (84 of 230; average, 1.7 relatives/index) of first-degree relatives of LSSP index cases (P = .03). Daughters were most likely to undergo CGT. CONCLUSIONS: A tumor screening program is more effective at detecting individuals with lower penetrant gene variants and families who do not meet traditional family history-based criteria. Cascade genetic testing is higher among clinic referrals compared with the screening program. These findings suggest a complementary role of these 2 ascertainment methods for Lynch syndrome.

Association of Ultra-processed Food and Unprocessed or Minimally Processed Food Consumption With Bowel Habits Among U.S. Adults.

BACKGROUND & AIMS: Ultra-processed foods (UPFs) may have a negative impact on bowel habits. We aimed to assess the association between UPF and unprocessed or minimally processed food (MPF) intake and bowel habits among adults in the United States (U.S.). METHODS: We performed a cross-sectional study using data from the National Health and Nutrition Examination Survey (2005-2010). We used two 24-hour dietary recalls and, based on the Nova classification, calculated intakes of UPFs and MPFs. Constipation and diarrhea were defined using the Bristol Stool Form Scale and stool frequency. We performed survey-weighted logistic regression and substitution analysis to estimate the odds ratios (ORs) and 95% confidence intervals (CIs). RESULTS: Among 12,716 U.S. adults, there were 1290 cases of constipation and 1067 cases of diarrhea. Median UPF and MPF intakes were 26.5% and 66.2% of total grams per day, respectively. Greater UPF consumption (in % gram/d) was associated with higher odds of constipation (adjusted OR [aORQ4 vs Q1], 2.20; 95% CI, 1.76-2.74) (Ptrend < .001) but not diarrhea (aORQ4 vs Q1, 0.82; 95% CI, 0.62-1.09) (Ptrend = .12). Increased MPF consumption was associated with lower odds of constipation (aORQ4 vs Q1, 0.46; 95% CI, 0.370-0.57) (Ptrend < .001). Associations with constipation were attenuated after adjusting for diet quality (aORQ4 vs Q1, UPF, 1.53; MPF, 0.69). Substituting 10% of UPF intake with an equivalent proportion of MPFs was associated with lower odds of constipation (aOR, 0.90; 95% CI, 0.87-0.93). CONCLUSIONS: UPF intake was associated with higher odds of constipation, whereas the odds were lower with greater MPF consumption. The effect of food processing on bowel habits was independent of diet quality.

Leaf functional traits and resource use strategies facilitate the spread of invasive plant Parthenium hysterophorus across an elevational gradient in western Himalayas.

Parthenium hysterophorus L. (Asteraceae) is a highly prevalent invasive species in subtropical regions across the world. It has recently been seen to shift from low (subtropical) to high (sub-temperate) elevations. Nevertheless, there is a dearth of research investigating the adaptive responses and the significance of leaf functional traits in promoting the expansion to high elevations. The current study investigated the variations and trade-offs among 14 leaf traits (structural, photosynthetic, and nutrient content) of P. hysterophorus across different elevations in the western Himalayas, India. Plots measuring 20 × 40 m were established at different elevations (700 m, 1100 m, 1400 m, and 1800 m) to collect leaf trait data for P. hysterophorus. Along the elevational gradient, significant variations were noticed in leaf morphological parameters, leaf nutrient content, and leaf photosynthetic parameters. Significant increases were observed in the specific leaf area, leaf thickness, and chlorophyll a, total chlorophyll and carotenoid content, as well as leaf nitrogen and phosphorus content with elevation. On the other hand, there were reductions in the amount of chlorophyll b, photosynthetic efficiency, leaf dry matter content, leaf mass per area, and leaf water content. The trait-trait relationships between leaf water content and dry weight and between leaf area and dry weight were stronger at higher elevations. The results show that leaf trait variability and trait-trait correlations are very important for sustaining plant fitness and growth rates in low-temperature, high-irradiance, resource-limited environments at relatively high elevations. To summarise, the findings suggest that P. hysterophorus can expand its range to higher elevations by broadening its functional niche through changes in leaf traits and resource utilisation strategies.

A Population-Based Matched Cohort Study of Digestive System Cancer Incidence and Mortality in Individuals With and Without Inflammatory Bowel Disease.

INTRODUCTION: To study digestive system cancer risks in individuals with inflammatory bowel diseases (IBDs) in the biologic era. METHODS: We used population-level administrative and cancer registry data from Ontario, Canada, (1994-2020) to compare people with IBD to matched controls (1:10 by sex and birth year) on trends in age-sex standardized cancer incidence and risk ratios of incident cancers and cancer-related deaths. RESULTS: Among 110,919 people with IBD and 1,109,190 controls, colorectal cancer incidence (per 100,000 person-years) declined similarly in people with ulcerative colitis (average annual percentage change [AAPC] -1.81; 95% confidence interval [CI] -2.48 to -1.156) and controls (AAPC -2.79; 95% CI -3.44 to -2.14), while small bowel cancer incidence rose faster in those with Crohn's disease (AAPC 9.68; 95% CI 2.51-17.3) than controls (AAPC 3.64; 95% CI 1.52-5.80). Extraintestinal digestive cancer incidence rose faster in people with IBD (AAPC 3.27; 95% CI 1.83-4.73) than controls (AAPC -1.87; 95% CI -2.33 to -1.42), particularly for liver (IBD AAPC 8.48; 95% CI 4.11-13.1) and bile duct (IBD AAPC 7.22; 95% CI 3.74-10.8) cancers. Beyond 2010, the incidences (and respective mortality rates) of colorectal (1.60; 95% CI 1.46-1.75), small bowel (4.10; 95% CI 3.37-4.99), bile duct (2.33; 95% CI 1.96-2.77), and pancreatic (1.19; 95% CI 1.00-1.40) cancers were higher in people with IBD. DISCUSSION: Cancer incidence is declining for colorectal cancer and rising for other digestive cancers in people with IBD. Incidence and mortality remain higher in people with IBD than controls for colorectal, small bowel, bile duct, and pancreatic cancers.

Forecasting the Incidence and Prevalence of Inflammatory Bowel Disease: A Canadian Nationwide Analysis.

INTRODUCTION: Canada has a high burden of inflammatory bowel disease (IBD). Historical trends of IBD incidence and prevalence were analyzed to forecast the Canadian burden over the next decade. METHODS: Population-based surveillance cohorts in 8 provinces derived from health administrative data assessed the national incidence (2007-2014) and prevalence (2002-2014) of IBD. Autoregressive integrated moving average models were used to forecast incidence and prevalence, stratified by age, with 95% prediction intervals (PI), to 2035. The average annual percentage change (AAPC) with 95% confidence interval (CI) was calculated for the forecasted incidence and prevalence. RESULTS: The national incidence of IBD is estimated to be 29.9 per 100,000 (95% PI 28.3-31.5) in 2023. With a stable AAPC of 0.36% (95% CI -0.05 to 0.72), the incidence of IBD is forecasted to be 31.2 per 100,000 (95% PI 28.1-34.3) in 2035. The incidence in pediatric patients (younger than 18 years) is increasing (AAPC 1.27%; 95% CI 0.82-1.67), but it is stable in adults (AAPC 0.26%; 95% CI -0.42 to 0.82). The prevalence of IBD in Canada was 843 per 100,000 (95% PI 716-735) in 2023 and is expected to steadily climb (AAPC 2.43%; 95% CI 2.32-2.54) to 1,098 per 100,000 (95% PI 1,068-1,127) by 2035. The highest prevalence is in seniors with IBD (1,174 per 100,000 in 2023; AAPC 2.78%; 95% CI 2.75-2.81). DISCUSSION: Over the next decade, the Canadian health care systems will contend with the juxtaposition of rising incidence of pediatric IBD and a rising prevalence of overall IBD driven by the aging population.

Inroads into saline-alkaline stress response in plants: unravelling morphological, physiological, biochemical, and molecular mechanisms.

MAIN CONCLUSION: This article discusses the complex network of ion transporters, genes, microRNAs, and transcription factors that regulate crop tolerance to saline-alkaline stress. The framework aids scientists produce stress-tolerant crops for smart agriculture. Salinity and alkalinity are frequently coexisting abiotic limitations that have emerged as archetypal mediators of low yield in many semi-arid and arid regions throughout the world. Saline-alkaline stress, which occurs in an environment with high concentrations of salts and a high pH, negatively impacts plant metabolism to a greater extent than either stress alone. Of late, saline stress has been the focus of the majority of investigations, and saline-alkaline mixed studies are largely lacking. Therefore, a thorough understanding and integration of how plants and crops rewire metabolic pathways to repair damage caused by saline-alkaline stress is of particular interest. This review discusses the multitude of resistance mechanisms that plants develop to cope with saline-alkaline stress, including morphological and physiological adaptations as well as molecular regulation. We examine the role of various ion transporters, transcription factors (TFs), differentially expressed genes (DEGs), microRNAs (miRNAs), or quantitative trait loci (QTLs) activated under saline-alkaline stress in achieving opportunistic modes of growth, development, and survival. The review provides a background for understanding the transport of micronutrients, specifically iron (Fe), in conditions of iron deficiency produced by high pH. Additionally, it discusses the role of calcium in enhancing stress tolerance. The review highlights that to encourage biomolecular architects to reconsider molecular responses as auxiliary for developing tolerant crops and raising crop production, it is essential to (a) close the major gaps in our understanding of saline-alkaline resistance genes, (b) identify and take into account crop-specific responses, and (c) target stress-tolerant genes to specific crops.

Neck circumference in polycystic ovary syndrome: a systematic review and bootstrapped meta-analysis with GRADE approach.

INTRODUCTION: Our aim was to perform a systematic review and meta-analysis for the association of neck circumference (NC) in polycystic ovary syndrome (PCOS) patients as compared to non-PCOS controls. METHODS: Primarily the PubMed/MEDLINE database, and others such as SCOPUS, Google Scholar, Cochrane Library, up to November 15, 2023 for observational studies comparing NC in PCOS versus non-PCOS women. The mean and SD values of NC and other covariates in PCOS and control groups were extracted by two independent reviewers, and the quality and risk of bias assessment was done using Newcastle-Ottawa Scale of the studies. The meta-analysis employed combined standardized mean differences (SMD) with 95% confidence intervals (CI) to compare NC between PCOS patients and controls. The heterogeneity and validity were addressed by sub-group, meta-regression, and sensitivity analyses. We conducted a Bootstrapped meta-analysis using 1000 and 10000 simulations to test the accuracy of the obtained results. The certainty of evidence was assessed by GRADE approach. RESULTS: Our meta-analysis included 9 observational studies. The PCOS patients showed a significantly higher NC values than the non-PCOS controls (SMD 0.66, 95% CI 0.41-0.91, p<0.0001). In the bootstrap meta-analysis, the accuracy of the observed findings was proved (SMD=0.66, CI=0.42 to 0.91) for the NC outcome. No publication bias was detected in the funnel plot analysis using Begg's and Egger's tests. The 95% prediction interval of 0.036 to 1.28, suggest that the true outcomes of the studies are generally in the same direction as the estimated average outcome. The sensitivity analysis provided the robustness of the outcome, and no single study was overly influential on the pooled estimate. CONCLUSION: This meta-analysis provides accurate evidence for significantly higher NC in PCOS as compared to non-PCOS controls. There is no sufficient evidence on the diagnostic accuracy measures for NC in PCOS. Hence, further research on its diagnostic utility in PCOS is needed.

An efficient strategy for evaluating new non-invasive screening tests for colorectal cancer: the guiding principles.

OBJECTIVE: New screening tests for colorectal cancer (CRC) are rapidly emerging. Conducting trials with mortality reduction as the end point supporting their adoption is challenging. We re-examined the principles underlying evaluation of new non-invasive tests in view of technological developments and identification of new biomarkers. DESIGN: A formal consensus approach involving a multidisciplinary expert panel revised eight previously established principles. RESULTS: Twelve newly stated principles emerged. Effectiveness of a new test can be evaluated by comparison with a proven comparator non-invasive test. The faecal immunochemical test is now considered the appropriate comparator, while colonoscopy remains the diagnostic standard. For a new test to be able to meet differing screening goals and regulatory requirements, flexibility to adjust its positivity threshold is desirable. A rigorous and efficient four-phased approach is proposed, commencing with small studies assessing the test's ability to discriminate between CRC and non-cancer states (phase I), followed by prospective estimation of accuracy across the continuum of neoplastic lesions in neoplasia-enriched populations (phase II). If these show promise, a provisional test positivity threshold is set before evaluation in typical screening populations. Phase III prospective studies determine single round intention-to-screen programme outcomes and confirm the test positivity threshold. Phase IV studies involve evaluation over repeated screening rounds with monitoring for missed lesions. Phases III and IV findings will provide the real-world data required to model test impact on CRC mortality and incidence. CONCLUSION: New non-invasive tests can be efficiently evaluated by a rigorous phased comparative approach, generating data from unbiased populations that inform predictions of their health impact.

Time Trends in Colorectal Cancer Incidence From 1992 to 2016 and Colorectal Cancer Mortality From 1980 to 2018 by Age Group and Geography in Canada.

INTRODUCTION: Several reports have highlighted increasing colorectal cancer (CRC) incidence among younger individuals. However, little is known about variations in CRC incidence or mortality across age subgroups in different geographical locations. We aimed to examine time trends in CRC incidence and mortality in Canada by age group and geography in this population-based, retrospective cohort study. METHODS: Individuals diagnosed with CRC from 1992 to 2016 or who died of CRC from 1980 to 2018 in Canada were studied. Geography was determined using an individual's postal code at diagnosis from the Canadian Cancer Registry or province or territory of death from the Canadian Vital Statistics Death Database. Geography was categorized into Atlantic, Central, Prairies, West, and Territories. Canadian Cancer Registry data were used to determine CRC incidence from 1992 to 2016. Canadian Vital Statistics Death data were used to determine CRC mortality from 1980 to 2018. RESULTS: Among all age groups, CRC incidence was highest in Atlantic Canada, was lowest in Western Canada, and increased with age. CRC incidence increased over time for individuals aged 20-44 years and was stable or decreased for other age groups in all regions. CRC mortality was highest in Atlantic Canada and lowest in the Prairies and Western Canada. CRC mortality decreased for individuals in all age groups and regions except among individuals aged 20-49 years in the Territories. DISCUSSION: Most of Canada has not yet seen an increase in CRC burden in the age group of 45-49 years, which is a reason to not lower the start age for CRC screening in Canada. Targeted CRC screening should be considered for individuals younger than 50 years who live in the Territories.

OPTIMIZING TIMING OF FOLLOW-UP COLONOSCOPY: A PILOT CLUSTER RANDOMIZED TRIAL OF A KNOWLEDGE TRANSLATION TOOL.

BACKGROUND: Endoscopists have low adherence to guideline recommended colonoscopy surveillance intervals. We performed a cluster randomized single-blind pilot trial in Winnipeg, Canada to assess the effectiveness of a newly developed digital application tool which computes guideline recommended follow-up intervals. METHODS: Participant endoscopists were randomized to either receive access to the digital application (intervention group) or not receive access (control group). Pathology reports and final recommendations for colonoscopies performed in the 1-4 months before randomization and 3-7 months post-randomization were extracted. Generalized estimating equation models were used to determine if the access to the digital application predicted guideline congruence. RESULTS: We included 15 endoscopists in the intervention group and 14 in the control group (out of 42 eligible endoscopists in the city), with 343 patients undergoing colonoscopy before randomization, and 311 post-randomization. Endoscopists who received the application made guideline-congruent recommendations 67.6% of the time prior to randomization and 76.1% of the time after randomization. Endoscopists in the control group made guideline- congruent recommendations 72.4% and 72.9% of the time pre- and post-randomization, respectively. Endoscopists in the intervention group trended to have an increase in guideline adherence comparing post to pre-intervention (OR:1.50, 95%CI 0.82-2.74). In contrast, the control group had no change in guideline adherence (OR:1.07, 95%CI 0.50-2.29). Endoscopists in the intervention group with less than median guideline congruence pre-randomization had a significant increase in guideline congruent recommendations post-randomization. CONCLUSION: An application that provides colonoscopy surveillance intervals may help endoscopists with guideline congruence, especially those with a lower pre-intervention congruence with guideline recommendations. (ClincialTrials.gov number, NCT04889352).

Sleep Disturbances, Bowel Movement Kinetics, and Travel Interruption With Bowel Preparation: A Bowel CLEANsing National Initiative Substudy.

INTRODUCTION: We investigated sleep disturbances, bowel movement (BM) kinetics, and travel experience with different bowel preparation regimens in a substudy of patients enrolled in a randomized multicenter Canadian clinical trial. METHODS: Patients scheduled to have a colonoscopy between 7:30 am and 10:30 am (early morning) were randomized to (i) 4-L single-dose polyethylene glycol (PEG) given in the evening before, (ii) 2-L split-dose PEG (+bisacodyl 15 mg), or (iii) 4-L split-dose PEG. Patients scheduled to undergo a colonoscopy between 10:30 am and 4:30 pm (afternoon) were randomized to (iv) 2-L single-dose PEG (+bisacodyl 15 mg) in the morning, (v) 2-L split-dose PEG (+bisacodyl 15 mg), or (vi) 4-L split-dose PEG. Patients were asked to record information on BM kinetics, sleep, and travel to the endoscopy unit. Continuous and categorical variables were compared between groups using a Kruskal-Wallis test or χ 2 test, respectively. Intention-to-treat analyses were performed. RESULTS: Overall, 641 patients were included in this substudy. Patients undergoing early morning colonoscopies reported the most awakenings in the night when assigned to 4-L single-dose day-before PEG and the highest reduction in sleep hours when assigned to 4-L split-dose PEG. There were no significant between-group differences in urgent BMs, fecal incontinence episodes, or travel interruptions. Overall, 17% of those traveling for more than an hour had to stop for a BM during travel, with no significant difference between groups. DISCUSSION: Day-before and split-dose high-volume PEG regimens for colonoscopies scheduled before 10:30 am lead to the greatest sleep disturbance.

A Canadian Provincial Screening Program for Lynch Syndrome.

INTRODUCTION: Manitoba implemented the first Canadian provincial program of reflex screening through mismatch repair immunohistochemistry (MMR-IHC) for all colorectal cancers diagnosed at age 70 years or younger in December 2017. We evaluated compliance to universal reflex testing and for referrals to Genetics for individuals with MMR-deficient tumors. METHODS: We searched the provincial pathology database with "adenocarcinoma" in the colorectal specimen pathology reports between March 2018 and December 2020. We cross-referenced with paper and electronic records in the Program of Genetics and Metabolism to determine whether patients with MMR-deficient tumors had been referred for Genetic assessment and what proportion of patients and first-degree relatives accepted an appointment and genetic testing. We performed logistic regression analysis to identify predictors of testing. RESULTS: We identified 3,146 colorectal adenocarcinoma specimens (biopsies and surgical resections) from 1,692 unique individuals (mean age 68.66 years, male 57%). Of those aged 70 years or younger (n = 936), 89.4% received MMR-IHC screening. Individual pathologists (categorized by the highest, average, and lowest screening rates) were the biggest predictors of MMR-IHC screening on multivariable analysis (highest vs lowest: odds ratio 17.5, 95% confidence interval 6.05-50.67). While only 53.4% (n = 31) of 58 screen-positive cases were referred by pathologists for genetic assessment, other clinicians referred an additional 22.4% (n = 13), resulting in 75.8% overall referral rate of screen-positive cases. Thirteen (1.4%) patients (1.1%, aged 70 years or younger) were confirmed to experience Lynch syndrome through germline testing, and 8 first-degree relatives (an average of 1.6 per patient) underwent cascade genetic testing. DISCUSSION: The first Canadian Lynch syndrome screening program has achieved high rates of reflex testing.

Deciphering the Mechanistic Basis for Perfluoroalkyl-Protein Interactions.

Although rarely used in nature, fluorine has emerged as an important elemental ingredient in the design of proteins with altered folding, stability, oligomerization propensities, and bioactivity. Adding to the molecular modification toolbox, here we report the ability of privileged perfluorinated amphiphiles to noncovalently decorate proteins to alter their conformational plasticity and potentiate their dispersion into fluorous phases. Employing a complementary suite of biophysical, in-silico and in-vitro approaches, we establish structure-activity relationships defining these phenomena and investigate their impact on protein structural dynamics and intracellular trafficking. Notably, we show that the lead compound, perfluorononanoic acid, is 106 times more potent in inducing non-native protein secondary structure in select proteins than is the well-known helix inducer trifluoroethanol, and also significantly enhances the cellular uptake of complexed proteins. These findings could advance the rational design of fluorinated proteins, inform on potential modes of toxicity for perfluoroalkyl substances, and guide the development of fluorine-modified biologics with desirable functional properties for drug discovery and delivery applications.

Mandatory vs. optional split-dose bowel preparation for morning colonoscopies: a pragmatic noninferiority randomized controlled trial.

BACKGROUND : We compared the effectiveness of optional split-dose bowel preparation (SDBP) with mandatory SDBP for morning colonoscopies in usual clinical practice. METHODS : Adult patients undergoing outpatient early morning (8:00 AM-10:30 PM) and late morning (10:30 AM-12:00 PM) colonoscopies were included. Written bowel preparation instructions were provided based on randomization: one group were instructed to take their bowel preparation (4 L polyethylene glycol solution) as a split dose (mandatory), while the comparator group was allowed the choice of SDBP or single-dose bowel preparation administered entirely on the day before (optional). The primary end point, using noninferiority hypothesis testing with a 5 % margin, was adequate bowel cleanliness measured by the Boston Bowel Preparation Scale (BBPS) and defined by a BBPS score ≥ 6. RESULTS : Among 770 randomized patients with complete data, there were 267 mandatory SDBP and 265 optional SDBP patients for early morning colonoscopies, and 120 mandatory SDBP and 118 optional SDBP patients for late morning colonoscopies. Optional SDBP was inferior to mandatory SDBP, with a lower proportion of adequate BBPS cleanliness for early morning colonoscopies (78.9 % vs. 89.9 %; absolute risk difference [aRD] 11.0 %, 95 %CI 5.9 % to 16.1 %), but was not statistically different for late morning colonoscopies (76.3 % vs. 83.3 %; aRD 7.1 %, 95 %CI -1.5 % to 15.5 %). CONCLUSIONS : Optional SDBP is inferior to mandatory SDBP in providing adequate bowel preparation quality for early morning colonoscopies (8:00 AM-10:30 AM), and probably inferior for late morning colonoscopies (10:30 AM-12:00 PM).

Recommendations for Optimal Endoscopic Localization of Colorectal Neoplasms: A Delphi Consensus of National Experts.

BACKGROUND: Colonoscopy is the standard of care for diagnosis and evaluation of colorectal cancers before surgery. However, varied practices and heterogenous documentation affects communication between endoscopists and operating surgeons, hampering surgical planning. OBJECTIVE: This study aimed to develop recommendations for the use of standardized localization and reporting practices for colorectal lesions identified during lower GI endoscopy. DESIGN: A systematic review of existing endoscopy guidelines and thorough narrative review of the overall endoscopy literature were performed to identify existing practices recommended globally. SETTING: An online Delphi process was used to establish consensus recommendations based on a literature review. PATIENTS: Colorectal surgeons and gastroenterologists from across Canada who had previously demonstrated leadership in endoscopy, managed large endoscopy programs, produced high-impact publications in the field of endoscopy, or participated in the development of endoscopy guidelines were selected to participate. PRIMARY OUTCOME MEASURES: The primary outcomes measured were colorectal lesion localization and documentation practice recommendations important to planning surgical or advanced endoscopic excisions. RESULTS: A total of 129 of 197 statements achieved consensus after 3 rounds of voting by 23 experts from across Canada. There was more than 90% participation in each round. Recommendations varied according to lesion location in the cecum, colon, or rectum and whether the referral was planned for surgical or advanced endoscopic resection. Recommendations were provided for appropriate documentation, indications, location, and method of tattoo placement, in addition to photograph and real-time 3-dimensional scope configuration device use. LIMITATIONS: Because of a paucity of evidence, recommendations are based primarily on expert opinion. There may be bias, as all representatives were based in Canada. CONCLUSIONS: Best practices to optimize endoscopic lesion localization and communication are not addressed in previous guidelines. This consensus involving national experts in colorectal surgery and gastroenterology provides a framework for efficient and effective colorectal lesion localization. See Video Abstract at http://links.lww.com/DCR/C71 . RECOMENDACIONES PARA LA LOCALIZACIN ENDOSCPICA PTIMA DE LAS NEOPLASIAS COLORRECTALES UN CONSENSO DELPHI DE EXPERTOS NACIONALES: ANTECEDENTES:La colonoscopia es el estándar de atención para el diagnóstico y la evaluación de los cánceres colorrectales antes de la cirugía. Sin embargo, las prácticas variadas y la documentación heterogénea afectan la comunicación entre los endoscopistas y los cirujanos operadores, lo que dificulta la planificación quirúrgica.OBJETIVO:Este estudio tuvo como objetivo desarrollar recomendaciones para el uso de prácticas estandarizadas de localización y notificación de lesiones colorrectales identificadas en la endoscopia gastrointestinal inferior.DISEÑO:Se realizó una revisión sistemática de las pautas de endoscopia existentes y una revisión narrativa exhaustiva de la literatura general sobre endoscopia para identificar las prácticas existentes recomendadas a nivel mundial. Se utilizó un proceso Delphi en línea para establecer recomendaciones de consenso basadas en la revisión de la literatura.PARTICIPANTES:Se seleccionaron para participar cirujanos colorrectales y gastroenterólogos de todo Canadá que previamente habían demostrado liderazgo en endoscopia, manejado grandes programas de endoscopia, producido publicaciones de alto impacto en el campo de la endoscopia o que habían participado en el desarrollo de pautas de endoscopia.RESULTADOS:Localización de lesiones colorrectales y recomendaciones prácticas de documentación importantes para planificar escisiones quirúrgicas o endoscópicas avanzadas.RESULTADOS:129 de 197 declaraciones lograron consenso después de tres rondas de votación de 23 expertos de todo Canadá. Hubo >90% de participación en cada ronda. Las recomendaciones variaron según la ubicación de la lesión en el ciego, colon o recto, y si se planificó la derivación para resección quirúrgica o endoscópica avanzada. Se proporcionaron recomendaciones para la documentación adecuada, las indicaciones, la ubicación y el método de colocación del tatuaje, además de la fotografía y el uso del dispositivo de configuración del alcance 3D en tiempo real.LIMITACIONES:Debido a la escasez de evidencia, las recomendaciones se basan principalmente en la opinión de expertos. Puede haber sesgo, ya que los representantes tenían su sede en Canadá.CONCLUSIONES:Las mejores prácticas para optimizar la localización y comunicación de lesiones endoscópicas no se abordan en las guías anteriores. Este consenso que involucra a expertos nacionales en cirugía colorrectal y gastroenterología proporciona un marco para la localización eficiente y efectiva de lesiones colorrectales. Consulte Video Resumen en http://links.lww.com/DCR/C71 . (Traducción-Dr. Mauricio Santamaria ).

Variability in Communication and Reporting Practices Between Gastroenterologists and General Surgeons Contributes to Repeat Preoperative Endoscopy for Colorectal Neoplasms: A Qualitative Analysis.

BACKGROUND: Surgeons commonly repeat preoperative endoscopy before planned colorectal resections. The reasons for this are not entirely clear, and repeat endoscopy may lead to delays in curative resection, increased costs, and patient discomfort. OBJECTIVE: This study aimed to determine practice patterns, localization techniques, and processes of communication undertaken by endoscopy specialists in a high-volume regional health authority. DESIGN: This was a qualitative study involving standardized, semi-structured, in-depth interviews that were conducted in person. Data were analyzed using a thematic analysis approach. SETTINGS: The study was conducted at Canadian tertiary and community facilities. PARTICIPANTS: Ten general surgeons and 10 gastroenterologists were included using a convenience sampling technique. MAIN OUTCOME MEASURES: Interview questions were developed to understand the perspectives and practice patterns of endoscopists when approaching patients diagnosed with colorectal lesions requiring surgical resection. The decision-making process to perform a repeat preoperative endoscopy was assessed. RESULTS: Three key themes emerged: 1) patterns of communication, 2) feedback, and 3) trust. Thematic analysis revealed that poor communication and ambiguous documentation increased the likelihood of performing repeat preoperative endoscopy. Inconsistencies in tattooing practices and lesion location were important factors. Negative experiences and factors related to interprofessional trust emerged as key contributors to repeat preoperative endoscopy. LIMITATIONS: The transferability of findings to health care systems outside Canada may be limited and requires further study. CONCLUSIONS: Suboptimal endoscopic reporting contributes to gaps in communication among endoscopists. In addition, lack of consistent feedback and mutual trust may increase the likelihood of performing repeat preoperative lower endoscopy. Inconsistent tattooing practices pose significant concerns for accurate intraoperative lesion localization. Establishing collaborative work environments through joint educational initiatives may enhance communication and mitigate unnecessary repeat procedures. These results support the need for standardized guidelines and endoscopic reporting in the management of colorectal lesions. See Video Abstract at http://links.lww.com/DCR/B879 . LA VARIABILIDAD EN LAS PRCTICAS DE COMUNICACIN Y PRESENTACIN DE INFORMES ENTRE GASTROENTERLOGOS Y CIRUJANOS GENERALES CONTRIBUYE A REPETIR LA ENDOSCOPIA PREOPERATORIA PARA LAS NEOPLASIAS COLORRECTALES UN ANLISIS CUALITATIVO: ANTECEDENTES:Los cirujanos suelen repetir la endoscopia preoperatoria antes de las resecciones colorrectales planificadas. Las razones de esto no están del todo claras y la repetición de la endoscopia puede provocar retrasos en la resección curativa, aumento de los costos y malestar del paciente.OBJETIVO:Nuestro objetivo fue determinar patrones de práctica, técnicas de localización y procesos de comunicación realizados por especialistas en endoscopia, en una autoridad sanitaria regional, de alto volumen.DISEÑO:Este fue un estudio cualitativo, que involucró entrevistas estandarizadas, semiestructuradas y en profundidad que se llevaron a cabo en persona. Los datos se analizaron mediante un enfoque de análisis temático.ENTORNO CLINICO:El estudio se llevó a cabo en instalaciones comunitarias y terciarias canadienses.PARTICIPANTES:Se incluyeron 10 cirujanos generales y 10 gastroenterólogos, utilizando una técnica de muestreo por conveniencia.PRINCIPALES MEDIDAS DE VALORACION:Las preguntas de la entrevista se desarrollaron para comprender las perspectivas y los patrones de práctica de los endoscopistas, cuando se acercan a pacientes diagnosticados con lesiones colorrectales que requieren resección quirúrgica. Se evaluó el proceso de toma de decisiones para realizar una nueva endoscopia preoperatoria.RESULTADOS:Surgieron tres temas clave: 1) patrones de comunicación, 2) retroalimentación y 3) confianza. El análisis temático reveló que la pobre comunicación y la ambigua documentación aumentaron la probabilidad de realizar una nueva endoscopia preoperatoria. Las inconsistencias en las prácticas de tatuaje y la ubicación de las lesiones fueron factores importantes. Las experiencias pasadas negativas y los factores relacionados con la confianza interprofesional surgieron como contribuyentes clave para repetir la endoscopia preoperatoria.LIMITACIONES:La transferibilidad de los hallazgos a los sistemas de atención médica fuera de Canadá, puede ser limitada y requiere más estudios.CONCLUSIONES:Los informes endoscópicos subóptimos contribuyen a las brechas en la comunicación entre los endoscopistas. Además, la falta de retroalimentación consistente y la confianza mutua pueden aumentar la probabilidad de realizar una nueva endoscopia baja preoperatoria. Las prácticas inconsistentes de tatuaje, plantean preocupaciones importantes para la localización precisa de las lesiones intraoperatorias. El establecimiento de entornos de trabajo colaborativo a través de iniciativas educativas conjuntas pueden mejorar la comunicación y mitigar la repetición de procedimientos innecesarios. Estos resultados apoyan la necesidad de pautas estandarizadas e informes endoscópicos en el tratamiento de las lesiones colorrectales. Consulte Video Resumen en http://links.lww.com/DCR/B879 . (Traducción-Dr. Fidel Ruiz Healy ).

An unnatural amino acid modified human insulin derivative for visual monitoring of insulin aggregation.

Insulin often forms toxic fibrils during production and transportation, which are deposited as amyloids at repeated injection sites in diabetic patients. Distinguishing early fibrils from non-fibrillated insulin is difficult. Herein, we introduce a chemically modified human insulin derivative with a distinct visual colour transition upon aggregation, facilitating insulin quality assessment.

Optimal endoscopic localization of colorectal neoplasms: a comparison of rural versus urban documentation practices.

BACKGROUND: Colonoscopy is the gold standard for diagnosing colorectal neoplasms. However, colonoscopy is often repeated preoperatively due to non-standard documentation and inconsistent practices by index endoscopists. Repeat endoscopies result in treatment delays and can increase risks of complications. National consensus recommendations were recently developed for optimal endoscopic colorectal lesion localization. We aimed to assess baseline colonoscopy practice differences from the new recommendations with a focus on geographical variability in report quality between urban and rural referral sites. METHODS: We performed a retrospective review of patients who underwent elective surgery for colorectal neoplasms at a single institution in Winnipeg between 2007-2020. We compared endoscopy report quality to the national recommendations with charts stratified by endoscopy location. Our primary outcomes were overall report documentation completeness and use of recommended practices. RESULTS: One hundred ninety-four patients were included (97 rural, 97 urban). The mean overall compliance with the recommendations for urban endoscopies was marginally better compared to rural endoscopies (50% vs. 48%, p = 0.04). Sixty-eight percent of the reports complied with tattoo indications (72% urban; 63% rural, p = 0.16). On average, reports included 29% of recommended tattoo information (30% urban; 28% rural, p = 0.25) and demonstrated 74% appropriate tattoo technique (70% urban; 81% rural, p = 0.10). Twenty-one percent of reports included photographs of lesions in accordance with the national recommendations (28% urban; 13% rural, p = 0.01). CONCLUSIONS: Endoscopists frequently omit recommended practices for optimal colorectal lesion localization. Rural reports miss more recommended information compared to urban reports. Future research is needed to facilitate province-wide high-quality endoscopy reporting for patients regardless of endoscopy location.

Comparison of synthetic and organic biodegradable chelants in augmenting cadmium phytoextraction in Solanum nigrum.

This study focused to enhance the cadmium (Cd) phytoextraction efficiency in Solanum nigrum by applying four biodegradable chelants (10 mM)-ethylene glycol tetraacetic acid (EGTA), ethylenediamine disuccinate (EDDS), nitrilotriacetic acid (NTA), and citric acid (CA), when grown in Cd-spiked soil (12 and 48 mg kg-1). Plant height, dry biomass, photosynthetic traits, and metal accumulation varied significantly with Cd and chelant treatments. Cadmium-toxicity resulted in reduction of plant growth and photosynthetic physiology, whereas chelant supplementation alleviated the toxic effect of Cd and increased its accumulation. Tolerance index value increased with addition of chelants in the order: EGTA (1.57-1.63) >EDDS (1.39-1.58) >NTA (1.14-1.50) >CA (1-1.22) compared with Cd (0.46-1.08). Transfer coefficient of root increased with supplementation of EGTA (3.40-3.85), EDDS (3.10-3.40), NTA (2.60-2.90), and CA (1.85-2.29), over Cd-alone (1.61-1.63). Similarly, translocation factor was also increased upon addition of EGTA (0.52-0.73), EDDS (0.35-0.81), NTA (0.38-0.75), and CA (0.53-0.54), compared with Cd-alone (0.36-0.59). Maximum Cd removal (67.67% at Cd12 and 36.05% at Cd48) was observed with supplementation of EGTA. The study concludes that the supplementation of EGTA and EDDS with S. nigrum can be employed as an efficient and environmentally safe technique for reclamation of Cd-contaminated soils.

Apart from the selection of a good hyperaccumulator, the choice of chelant (biodegradable/non-biodegradable) is an important aspect for the successful phytoextraction of metals from contaminated soil. We reported for the first time the potential of ethylene glycol tetraacetic acid (EGTA; a biodegradable chelant) in enhancing Cd phytoextraction by Solanum nigrum. Comparative appraisal of metal extraction efficiency of biodegradable chelants at low (12 mg kg⁻¹) and high (48 mg kg⁻¹) Cd dose depicted that EGTA performed better than EDDS, NTA, and CA (other biodegradable chelants). EGTA supplementation did not induce toxicity in plants; rather it improved metal accumulation, morphology, and photosynthetic physiology.