RISK FACTORS FOR METACHRONOUS COLORECTAL CANCER OR ADVANCED LESIONS AFTER ENDOSCOPIC RESECTION OF SERRATED POLYPS: A SYSTEMATIC REVIEW AND META-ANALYSIS.

BACKGROUND AND AIMS: Serrated polyps (SPs) are precursors to 15-20% of colorectal cancers (CRCs). However, there are uncertainties regarding which SPs require surveillance and at what intervals, with recommendations adapted from those for adenomas in the absence of solid evidence. Our aim was to assess which SP risk characteristics relate to a higher risk of metachronous CRC or advanced polyps. METHODS: We systematically searched PubMed, EMBASE, and Cochrane for cohort, case-control studies, and clinical trials from inception to Dec 31, 2023, for CRC or advanced polyps [advanced adenoma (AA) or advanced SP] incidence at surveillance stratified by baseline SP size, dysplasia, location, and multiplicity. We defined advanced SPs as those >10mm or with dysplasia. CRC and advanced polyp incidence per 1,000 person-years (p-y) were estimated. We performed a meta-analysis by calculating pooled relative risks (RR) using a random-effects model. RESULTS: 5,903 studies were reviewed and 14 included, with 493,949 patients (mean age 59·5 years, 55% men). Mean follow-up was 4·9 years. CRC incidence per 1,000 p-y was 2·09 (95%CI 1·29-2·90) for advanced SP, 1·52 (0·78-2·25) for SP>10mm, 5·86 (2·16-9·56) for SP with dysplasia, 1·18 (0·77-1·60) for proximal SP, 0·52 (0·08-1·12) for >3SP, 0·50 (0·35-0·66) for non-advanced SP, and 0·44 (0·41-0·46) for normal colonoscopy. Metachronous CRC risk was higher in advanced SP vs non-advanced SP (RR 1·84, 95%CI 1·11-3·04), and vs normal colonoscopy (RR 2·92, 2·26-3·77); in SP>10mm vs <10mm (RR 2·61, 1·43-4·77), and vs normal colonoscopy (RR 3·52, 2·17-5·69); and in SP with dysplasia vs normal colonoscopy (RR 2·71, 2·00-3·67). No increase in CRC or advanced polyp risk was found in patients with proximal vs distal SP, nor in >3SP vs 1-2SP. CONCLUSIONS: CRC risk is significantly higher in patients with baseline advanced SP after 4·9 years of follow-up, with risk magnitudes similar to those described for AA, supporting the current recommendation for 3-year surveillance in patients with advanced SP.

Role of Artificial Intelligence in Colonoscopy Detection of Advanced Neoplasias : A Randomized Trial.

BACKGROUND: The role of computer-aided detection in identifying advanced colorectal neoplasia is unknown. OBJECTIVE: To evaluate the contribution of computer-aided detection to colonoscopic detection of advanced colorectal neoplasias as well as adenomas, serrated polyps, and nonpolypoid and right-sided lesions. DESIGN: Multicenter, parallel, randomized controlled trial. (ClinicalTrials.gov: NCT04673136). SETTING: Spanish colorectal cancer screening program. PARTICIPANTS: 3213 persons with a positive fecal immunochemical test. INTERVENTION: Enrollees were randomly assigned to colonoscopy with or without computer-aided detection. MEASUREMENTS: Advanced colorectal neoplasia was defined as advanced adenoma and/or advanced serrated polyp. RESULTS: The 2 comparison groups showed no significant difference in advanced colorectal neoplasia detection rate (34.8% with intervention vs. 34.6% for controls; adjusted risk ratio [aRR], 1.01 [95% CI, 0.92 to 1.10]) or the mean number of advanced colorectal neoplasias detected per colonoscopy (0.54 [SD, 0.95] with intervention vs. 0.52 [SD, 0.95] for controls; adjusted rate ratio, 1.04 [99.9% CI, 0.88 to 1.22]). Adenoma detection rate also did not differ (64.2% with intervention vs. 62.0% for controls; aRR, 1.06 [99.9% CI, 0.91 to 1.23]). Computer-aided detection increased the mean number of nonpolypoid lesions (0.56 [SD, 1.25] vs. 0.47 [SD, 1.18] for controls; adjusted rate ratio, 1.19 [99.9% CI, 1.01 to 1.41]), proximal adenomas (0.94 [SD, 1.62] vs. 0.81 [SD, 1.52] for controls; adjusted rate ratio, 1.17 [99.9% CI, 1.03 to 1.33]), and lesions of 5 mm or smaller (polyps in general and adenomas and serrated lesions in particular) detected per colonoscopy. LIMITATIONS: The high adenoma detection rate in the control group may limit the generalizability of the findings to endoscopists with low detection rates. CONCLUSION: Computer-aided detection did not improve colonoscopic identification of advanced colorectal neoplasias. PRIMARY FUNDING SOURCE: Medtronic.

Risk Factors for Metachronous Colorectal Cancer or Advanced Adenomas After Endoscopic Resection of High-risk Adenomas.

BACKGROUND & AIMS: Among the characteristics of high-risk adenomas (HRAs), some may predict a higher risk of metachronous advanced lesions. Our aim was to assess which HRA characteristics are associated with high risk of metachronous colorectal cancer (CRC) or advanced adenomas (AAs). METHODS: We systematically searched Pubmed, EMBASE, and Cochrane for cohort studies and clinical trials of CRC or AA incidence at surveillance stratified by baseline lesion size, histology, and multiplicity. We calculated pooled relative risks (RRs) using a random-effects model. Heterogeneity was assessed with the I2 statistic. RESULTS: Fifty-five studies were included, with 936,540 patients with mean follow-up 5.4 ± 2.9 years. CRC incidence per 1000 person-years was 2.6 (2.1-3.0) for adenomas ≥20 mm, 2.7 (2.2-3.2) for high-grade dysplasia (HGD), 2.0 (1.8-2.3) for villous component, 0.8 (0.1-1.4) for ≥5 adenomas, 1.0 (0.7-1.2) for ≥3 adenomas. Metachronous CRC risk was higher in adenomas ≥20 mm vs 10 to 19 mm (RR, 2.08; 95% confidence interval [CI], 1.20-3.61), HGD vs low-grade dysplasia (RR, 2.89; 95% CI, 1.88-4.44), villous vs tubular (RR, 1.75; 95% CI, 1.33-2.31). No significant differences in CRC risk were found in ≥3 adenomas vs 1 to 2 (RR, 1.24; 95% CI, 0.84-1.83), nor in ≥5 adenomas vs 3 to 4 (RR, 0.79; 95% CI, 0.30-2.11). Compared with normal colonoscopy, RR for CRC risk was 2.61 (95% CI, 2.06-3.32) for ≥10mm, 6.62 (95% CI, 4.60-9.52) for HGD, 3.58 (95% CI, 2.24-5.73) for villous component, and 2.03 (95% CI, 1.40-2.94) for ≥3 adenomas. Similar trends were seen for metachronous AAs. CONCLUSION: Metachronous CRC risk is highest in patients with baseline adenomas with ≥20 mm or HGD. Multiplicity does not seem to be associated with substantially higher CRC risk in the near term.

Reference intervals for bone turnover markers in Spanish premenopausal women.

BACKGROUND: The aims of this study were to establish robust reference intervals and to investigate the factors influencing bone turnover markers (BTMs) in healthy premenopausal Spanish women. METHODS: A total of 184 women (35-45 years) from 13 centers in Catalonia were analyzed. Blood and second void urine samples were collected between 8 a.m. and 10 a.m. after an overnight fast. Serum procollagen type I amino-terminal propeptide (PINP) and serum cross-linked C-terminal telopeptide of type I collagen (CTX-I) were measured by two automated assays (Roche and IDS), bone alkaline phosphatase (bone ALP) by ELISA, osteocalcin (OC) by IRMA and urinary NTX-I by ELISA. PTH and 25-hydroxyvitamin D (25OHD) levels were measured. All participants completed a questionnaire on lifestyle factors. RESULTS: Reference intervals were: PINP: 22.7-63.1 and 21.8-65.5 µg/L, bone ALP: 6.0-13.6 µg/L, OC: 8.0-23.0 µg/L, CTX-I: 137-484 and 109-544 ng/L and NTX-I: 19.6-68.9 nM/mM. Oral contraceptive pills (OCPs) influenced PINP (p=0.007), and low body mass index (BMI) was associated with higher BTMs except for bone ALP. Women under 40 had higher median values of most BTMs. CTX-I was influenced by calcium intake (p=0.010) and PTH (p=0.007). 25OHD levels did not influence BTMs. Concordance between the two automated assays for PINP and particularly CTX-I was poor. CONCLUSIONS: Robust reference intervals for BTMs in a Southern European country are provided. The effects of OCPs and BMI on their levels are significant, whilst serum 25OHD levels did not influence BTMs. Age, calcium intake, BMI and PTH influenced CTX-I. The two automated assays for measuring PINP and CTX-I are not interchangeable.

Incidence, characteristics, and predictive factors of post-colonoscopy colorectal cancer.

BACKGROUND: Post-colonoscopy colorectal cancer (PCCRC) is colorectal cancer (CRC) diagnosed after a colonoscopy in which no cancer is found. OBJECTIVE: As PCCRC has become an important quality indicator, we determined its rates, characteristics, and index colonoscopy-related predictive factors. METHODS: We carried out a multicenter, observational, retrospective study between 2015 and 2018. Rates were calculated for PCCRC developing up to 10 years after colonoscopy. PCCRC was categorized according to the most plausible explanation using World Endoscopy Organization methodology. Our PCCRC population was compared to a control cohort without CRC matched 1:4 by sex, age, index colonoscopy date, indication, endoscopist, and hospital. RESULTS: One hundred seven PCCRC and 2508 detected CRC were diagnosed among 101,524 colonoscopy (0.1%), leading to rates of 0.4%, 2.2%, 3.1%, and 4.1% at 1, 3, 5, and 10 years, respectively. PCCRC was in right (42.4%), left (41.4%), and transverse (16.4%) colon with 31.5% at stage I, 24.7% stage II, 32.6% stage III, and 11.2% stage IV. Twenty point three percent were classified as incomplete resection, 5.4% as unresected lesions, 48.6% as missed lesions with adequate colonoscopy, and 25.7% as missed lesions with inadequate colonoscopy. The median time from colonoscopy to PCCRC was 42 months. Previous inadequate preparation (OR 3.05, 95%CI 1.73-5.36) and piecemeal polypectomy (OR 19.89, 95%CI 8.67-45.61) were independently associated with PCCRC. CONCLUSIONS: In our population, 4.1% of CRC cases were PCCRC. Most of these lesions were in right colon and attributable to lesions not visualized despite adequate bowel cleansing. Previous inadequate cleansing and piecemeal polypectomy were associated with PCCRC.

Effect of the SARS-CoV-2 pandemic on colorectal cancer diagnosis and prognosis.

BACKGROUND AND STUDY AIMS: Our aim was to determine the impact of the SARS-CoV-2 pandemic on the diagnosis and prognosis of colorectal cancer (CRC). PATIENTS AND METHODS: This prospective cohort study included individuals diagnosed with CRC between March 13, 2019 and June 20, 2021 across 21 Spanish hospitals. Two time periods were compared: prepandemic (from March 13, 2019 to March 13, 2020) and pandemic (from March 14, 2020 to June 20, 2021, lockdown period and 1 year after lockdown). RESULTS: We observed a 46.9% decrease in the number of CRC diagnoses (95% confidence interval (CI): 45.1%-48.7%) during the lockdown and 29.7% decrease (95% CI: 28.1%-31.4%) in the year after the lockdown. The proportion of patients diagnosed at stage I significantly decreased during the pandemic (21.7% vs. 19.0%; p = 0.025). Centers that applied universal preprocedure SARS-CoV-2 PCR testing experienced a higher reduction in the number of colonoscopies performed during the pandemic post-lockdown (34.0% reduction; 95% CI: 33.6%-34.4% vs. 13.7; 95% CI: 13.4%-13.9%) and in the number of CRCs diagnosed (34.1% reduction; 95% CI: 31.4%-36.8% vs. 26.7%; 95% CI: 24.6%-28.8%). Curative treatment was received by 87.5% of patients diagnosed with rectal cancer prepandemic and 80.7% of patients during the pandemic post-lockdown period (p = 0.002). CONCLUSIONS: The COVID-19 pandemic has led to a decrease in the number of diagnosed CRC cases and in the proportion of stage I CRC. The reduction in the number of colonoscopies and CRC diagnoses was higher in centers that applied universal SARS-CoV-2 PCR screening before colonoscopy. In addition, the COVID-19 pandemic has affected curative treatment of rectal cancers.

Automated discrimination of proximal right coronary artery occlusion from middle-to-distal right coronary artery occlusion and left circumflex occlusion in ST-elevation myocardial infarction.

BACKGROUND: Classifying the location of an occlusion in the culprit artery during ST-elevation myocardial infarction (STEMI) is important for risk stratification to optimize treatment. We developed a new logistic regression (LR) algorithm for 3-group classification of occlusion location as proximal right coronary artery (RCA), middle-to-distal RCA or left circumflex (LCx) coronary artery with inferior myocardial infarction. We compared the performance of the new LR algorithm with the recently introduced decision tree classifier of Fiol et al (Ann Noninvasive Electrocardiol. 2004;4:383-388) in the classification of the same 3 categories. METHODS: The new algorithm was developed on a set of electrocardiograms from an emergency department setting (n = 64) and tested on a different set from a prehospital setting (n = 68). All patients met the current STEMI criteria with angiographic confirmation of culprit artery and occlusion location. Using LR, 4 ST-segment deviation features were chosen by forward stepwise selection. Final LR coefficients were obtained by averaging more than 200 bootstrap iterations on the training set. In addition, a separate 4-feature classifier was designed adding ST features of V4R and V8, only available in the training set. RESULTS: The LR algorithm classified proximal RCA occlusion vs combined LCx occlusion and middle-to-distal RCA occlusion, with a sensitivity of 76% and specificity of 81% as compared with 71% and 62% for the Fiol classifier. The difference in specificity was statistically significant. The LR classifier trained with additional ST features of V4R and V8, but still limited to 4, improved the overall agreement in the training set from 65% to 70%. CONCLUSION: Discrimination of proximal RCA lesion location from LCx or middle-to-distal RCA using the new LR classifier shows improvement over decision tree-type classification criteria. Automated identification of proximal RCA occlusion could speed up the risk stratification of patients with STEMI. The addition of leads V4R and V8 should further improve the automated classification of the occlusion site in RCA and LCx.

Automated discrimination of proximal right coronary artery occlusion from middle-to-distal right coronary artery occlusion and left circumflex occlusion in ST-elevation myocardial infarction.

BACKGROUND: Classifying the location of an occlusion in the culprit artery during ST-elevation myocardial infarction (STEMI) is important for risk stratification to optimize treatment. We developed a new logistic regression (LR) algorithm for 3-group classification of occlusion location as proximal right coronary artery (RCA), middle-to-distal RCA or left circumflex (LCx) coronary artery with inferior myocardial infarction. We compared the performance of the new LR algorithm with the recently introduced decision tree classifier of Fiol et al (Ann Noninvasive Electrocardiol. 2004;4:383-388) in the classification of the same 3 categories. METHODS: The new algorithm was developed on a set of electrocardiograms from an emergency department setting (n = 64) and tested on a different set from a prehospital setting (n = 68). All patients met the current STEMI criteria with angiographic confirmation of culprit artery and occlusion location. Using LR, 4 ST-segment deviation features were chosen by forward stepwise selection. Final LR coefficients were obtained by averaging more than 200 bootstrap iterations on the training set. In addition, a separate 4-feature classifier was designed adding ST features of V4R and V8, only available in the training set. RESULTS: The LR algorithm classified proximal RCA occlusion vs combined LCx occlusion and middle-to-distal RCA occlusion, with a sensitivity of 76% and specificity of 81% as compared with 71% and 62% for the Fiol classifier. The difference in specificity was statistically significant. The LR classifier trained with additional ST features of V4R and V8, but still limited to 4, improved the overall agreement in the training set from 65% to 70%. CONCLUSION: Discrimination of proximal RCA lesion location from LCx or middle-to-distal RCA using the new LR classifier shows improvement over decision tree­type classification criteria. Automated identification of proximal RCA occlusion could speed up the risk stratification of patients with STEMI. The addition of leads V4R and V8 should further improve the automated classification of the occlusion site in RCA and LCx.

Conduction Disorders in the Setting of Acute STEMI.

ST-elevation myocardial (STEMI) is frequently associated with conduction disorders. Regional myocardial ischemia or injury may affect the cardiac conduction system at various locations, and neural reflexes or changes in the balance of the autonomous nervous system may be involved. Sinoatrial and atrioventricular blocks are more frequent in inferior than anterior STEMI, while new left anterior fascicular block and right bundle branch block indicate proximal occlusion of the left anterior descending coronary artery. New left bundle branch block is associated with multi-vessel disease. Most conduction disorders associated with STEMI are reversible with reperfusion therapy, but they may still impair prognosis because they indicate a large area at risk, extensive myocardial infarction or severe coronary artery disease. Acute STEMI recognition is possible in patients with a fascicular or right bundle branch block, but future studies need to define the cut-off values for ST depression in the leads V1-V3 in inferolateral MI and for ST elevation in the same leads in anterior STEMI. In the left bundle branch block, concordant ST elevation is a specific sign of acute coronary artery occlusion, but the ECG feature has low sensitivity.

Concordance between direct and indirect measurements of free 25-OH vitamin D.

At present, data comparing the quantification methods for measurement of free vitamin D (direct assay [direct 25-OHDF] and estimated by calculation [calculated 25-OHDF]), are scarce. The aim of this study was to analyse the concordance between these two methods of 25-OHDF analysis (direct vs. calculated). METHODS: Serum values of total 25-OHD (25-OHDT), vitamin D binding protein (DBP) (by R&D Systems ELISA), calculated 25-OHDF (by DBP, albumin and 25-OHDT) and direct 25-OHDF (by DIAsource ELISA) were analysed in 173 healthy women (aged 35-45years). Assessment of concordance was evaluated by the Bland-Altman plot and the total deviation index (TDI). RESULTS: The mean values of calculated and direct 25-OHDF in these subjects were 5.27±2.5 and 3.83±1.01pg/mL, respectively. We found significantly lower values of 25-OHDF on comparing subjects with and without vitamin D deficiency, independently of the method used. The total deviation index evaluated by the Bland-Altman plot showed low concordance for both measurements. Only low 25-OHDF levels were concordant. CONCLUSIONS: This study shows that the concordance between these two methods of 25-OHDF analysis is low and has a concentration dependent bias. Further studies are necessary to clarify the reference values and the indications for 25-OHDF measurement.

Chloride and sulphate toxicity to Hydropsyche exocellata (Trichoptera, Hydropsychidae): Exploring intraspecific variation and sub-lethal endpoints.

The rivers and streams of the world are becoming saltier due to human activities. In spite of the potential damage that salt pollution can cause on freshwater ecosystems, this is an issue that is currently poorly managed. Here we explored intraspecific differences in the sensitivity of freshwater fauna to two major ions (Cl(-) and SO4(2-)) using the net-spinning caddisfly Hydropsyche exocellata Dufour 1841 (Trichoptera, Hydropsychidae) as a model organism. We exposed H. exocellata to saline solutions (reaching a conductivity of 2.5mScm(-1)) with Cl(-):SO4(2-) ratios similar to those occurring in effluents coming from the meat, mining and paper industries, which release dissolved salts to rivers and streams in Spain. We used two different populations, coming from low and high conductivity streams. To assess toxicity, we measured sub-lethal endpoints: locomotion, symmetry of the food-capturing nets and oxidative stress biomarkers. According to biomarkers and net building, the population historically exposed to lower conductivities (B10) showed higher levels of stress than the population historically exposed to higher conductivities (L102). However, the differences between populations were not strong. For example, net symmetry was lower in the B10 than in the L102 only 48h after treatment was applied, and biomarkers showed a variety of responses, with no discernable pattern. Also, treatment effects were rather weak, i.e. only some endpoints, and in most cases only in the B10 population, showed a significant response to treatment. The lack of consistent differences between populations and treatments could be related to the high salt tolerance of H. exocellata, since both populations were collected from streams with relatively high conductivities. The sub-lethal effects tested in this study can offer an interesting and promising tool to monitor freshwater salinization by combining physiological and behavioural bioindicators.

Can salinity trigger cascade effects on streams? A mesocosm approach.

Human activities have greatly increased the salt concentration of the world's rivers, and this might be amplified by water scarcity in the future. While the lethal effects of salinity have been documented for a wide variety of stream invertebrates, the sub-lethal effects (i.e. changes in biological condition without mortality) are not deeply understood yet. One important sub-lethal effect that has yet to be investigated is changes in predation efficiency, which could trigger cascade effects associated to the abundance of herbivorous invertebrates that control algae biomass. In this study we combined the use of biomarkers with community-level data in a stream mesocosm to evaluate the potential cascade effect of increased salinity on the trophic food web. Both predation and salt treatments had an effect on the aquatic invertebrate abundance, richness and community composition. The presence of predators had a clear cascade effect, it reduced herbivorous invertebrate abundance and richness leading to higher chlorophyll a concentrations. The salt treatment significantly reduced taxa richness, but only in the gravel bed. The predators were significantly stressed by salt addition, as shown by the different analyzed biomarkers. Concordantly, in the presence of predators, Tanytarsini registered higher abundances and chlorophyll a showed a lower concentration when salt was added. However, none of these changes was significant. Therefore, although salt addition significantly stressed Dina lineata, our results suggest that a longer exposure time is needed to fully capture cascading effects (e.g. a decrease in chlorophyll a due to a relaxation of predation on herbivorous invertebrates). We suggest that the potential cascade effects of salinization need to be evaluated when addressing the impacts of water scarcity (as caused by climate change and increasing water demand) on river ecosystems, since flow reductions will lead to higher salt concentrations.

Sucralfate therapy in NSAID bleeding gastropathy.

BACKGROUND AND AIMS: A randomized, double-blind, placebo-controlled, multicenter study was conducted to assess the efficacy of 2 g sucralfate suspension in treating gastric mucosal lesions caused by long-term treatment with nonsteroidal anti-inflammatory drugs (NSAIDs). METHODS: Only patients given NSAIDs continuously for at least 2 months with positive fecal occult blood (FOB) and endoscopically confirmed mild to moderate mucosal lesions (Lanza scale, grades 2-4) were included. After 1-week run-in phase, patients were stratified into 2 groups according to gastropathy-related symptoms during the preceding 7 days (symptomatic vs. asymptomatic) and randomized to 2 g (10 mL) of sucralfate suspension or placebo twice a day over a 6-week period. NSAIDs were given according to each patient's dosage schedule and always after meals. RESULTS: Twenty-five patients received sucralfate and 25 received placebo. At the end of the study, 68% (17/25) of patients given sucralfate had no lesions (Lanza grade 0) on endoscopy compared with 35% (8/23) in controls (P = 0.042). The Lanza grades in patients given sucralfate were significantly improved compared with the placebo patients (P = 0.022). CONCLUSIONS: In this target population selected according to positive FOB test and endoscopic evidence of mucosal injury, chronic administration of sucralfate significantly decreased NSAID-induced gastric erosions.