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There is an increasing interest in inappropriate proton pump inhibitors prescription (InPPIp), as defined by the National Institute for Clinical Excellence (NICE) guidelines.To evaluate the rate, trend over time and factors associated with InPPIp upon discharge from internal medicine departments.We evaluated patients discharged from internal medicine departments with a PPI prescription in 2014 and 2017 at an academic referral center according to a developed algorithm.A total of 3,982 patients were included (50.8% women, 74% ≥ 65 years). The rate of InPPIp was 44.3% (95% CI 42.8-45.9) for the entire cohort; 68.1% for subjects aged65 years and 36.0% for those aged ≥ 65 years (p0.001); 43.2% in 2014 and 45.6% in 2017 (p = 0.130). In a decision-tree analysis, after the exclusion of 448 patients with gastrointestinal indications, 89.4% (1,580/1,766) of all InPPIp cases were of patients without dual antiplatelet treatment (DAPT) and 8.6% (151/1,766) were of patients younger than 65 years, who were taking aspirin.The rate of InPPIp is high, especially among patients not receiving DAPT and young patients taking aspirin. Time trend analysis showed no improvement over time. Our algorithm may serve as an automated quality measuring tool to reduce InPPIp.

Current guidelines are inconsistent regarding the follow-up of patients with 1-2 diminutive (1-5 mm) non-advanced adenomas (DNAAs).To evaluate the risk of metachronous advanced neoplasia (AN), defined as cancer or advanced adenoma (AA), among patients with either normal colonoscopy or 1-2 DNAAs.A retrospective cohort study. Cohort I included 2,347 subjects with normal colonoscopy and 483 subjects with polypectomy of 1-2 DNAAs followed by colonoscopy. Cohort II included 11,881 subjects with normal colonoscopy and 1,342 subjects with 1-2 DNAAs followed through the cancer registry.In cohort I, the rate of AN, cancer and AA among the polypectomy group vs. normal colonoscopy was 5.0% vs. 2.5%, Hazard Ratio (HR) 2.96 (95%CI [Confidence Interval]1.86-4.78) for AN; 0.6% vs. 0.3%, HR 3.32 (95%CI 0.85-13) for cancer; 4.3% vs. 2.2% HR 2.91 (95%CI 1.75-4.86) for AA. In cohort II, cancer occurred in 0.4% of the polypectomy group and 0.2% of the normal colonoscopy group, HR 2.27 (95% CI 0.56-9.19).Compared to subjects with normal colonoscopy, subjects with polypectomy of 1-2 DNAAs, are at increased risk for AA when followed by colonoscopy, while the risk for cancer is non-significantly increased. Our findings suggest that patients with 1-2 DNNAs should be followed more tightly than patients with normal colonoscopy.

We present a method for constructing seamless parametrization for surfaces of any genus, which can handle any feasible cone configuration with any type of cones. The mapping is guaranteed to be locally injective, which is due to careful construction of a simple domain boundary polygon. The polygon’s complexity depends on the cones in the field, and it is independent of mesh geometry. The result is a small polygon that can be optimized prior to the interior mapping, which contributes to the robustness of the pipeline. For a surface of genus > 0, non-contractible loops play an important role, and their holonomies significantly affect mapping quality. We enable holonomy prescription, where local injectivity is guaranteed. Our prescription, however, is limited and cannot handle all feasible holonomies due to monotonicity constraints that keep our polygon simple. Yet, this work is an important step towards fully solving the holonomy prescription problem.

Background: The Prospective Lynch Syndrome Database (PLSD) collates information on carriers of pathogenic or likely pathogenic MMR variants (path_MMR) who are receiving medical follow-up, including colonoscopy surveillance, which aims to the achieve early diagnosis and treatment of cancers. Here we use the most recent PLSD cohort that is larger and has wider geographical representation than previous versions, allowing us to present mortality as an outcome, and median ages at cancer diagnoses for the first time.Methods: The PLSD is a prospective observational study without a control group that was designed in 2012 and updated up to October 2022. Data for 8500 carriers of path_MMR variants from 25 countries were included, providing 71,713 years of follow up. Cumulative cancer incidences at 65 years of age were combined with 10-year crude survival following cancer, to derive estimates of mortality up to 75 years of age by organ, gene, and gender.Findings: Gynaecological cancers were more frequent than colorectal cancers in path_MSH2, path_MSH6 and path_PMS2 carriers [cumulative incidence: 53.3%, 49.6% and 23.3% at 75 years, respectively]. Endometrial, colon and ovarian cancer had low mortality [8%, 13% and 15%, respectively] and prostate cancers were frequent in male path_MSH2 carriers [cumulative incidence: 39.7% at 75 years]. Pancreatic, brain, biliary tract and ureter and kidney and urinary bladder cancers were associated with high mortality [83%, 66%, 58%, 27%, and 29%, respectively]. Among path_MMR carriers undergoing colonoscopy surveillance, particularly path_MSH2 carriers, more deaths followed non-colorectal Lynch syndrome cancers than colorectal cancers.Interpretation: In path_MMR carriers undergoing colonoscopy surveillance, non-colorectal Lynch syndrome cancers were associated with more deaths than were colorectal cancers. Reducing deaths from non-colorectal cancers presents a key challenge in contemporary medical care in Lynch syndrome. Background: The Prospective Lynch Syndrome Database (PLSD) collates information on carriers of pathogenic or likely pathogenic MMR variants (path_MMR) who are receiving medical follow-up, including colonoscopy surveillance, which aims to the achieve early diagnosis and treatment of cancers. Here we use the most recent PLSD cohort that is larger and has wider geographical representation than previous versions, allowing us to present mortality as an outcome, and median ages at cancer diagnoses for the first time. Methods: The PLSD is a prospective observational study without a control group that was designed in 2012 and updated up to October 2022. Data for 8500 carriers of path_MMR variants from 25 countries were included, providing 71,713 years of follow up. Cumulative cancer incidences at 65 years of age were combined with 10-year crude survival following cancer, to derive estimates of mortality up to 75 years of age by organ, gene, and gender. Findings: Gynaecological cancers were more frequent than colorectal cancers in path_MSH2, path_MSH6 and path_PMS2 carriers [cumulative incidence: 53.3%, 49.6% and 23.3% at 75 years, respectively]. Endometrial, colon and ovarian cancer had low mortality [8%, 13% and 15%, respectively] and prostate cancers were frequent in male path_MSH2 carriers [cumulative incidence: 39.7% at 75 years]. Pancreatic, brain, biliary tract and ureter and kidney and urinary bladder cancers were associated with high mortality [83%, 66%, 58%, 27%, and 29%, respectively]. Among path_MMR carriers undergoing colonoscopy surveillance, particularly path_MSH2 carriers, more deaths followed non-colorectal Lynch syndrome cancers than colorectal cancers. Interpretation: In path_MMR carriers undergoing colonoscopy surveillance, non-colorectal Lynch syndrome cancers were associated with more deaths than were colorectal cancers. Reducing deaths from non-colorectal cancers presents a key challenge in contemporary medical care in Lynch syndrome. Funding: We acknowledge funding from the Norwegian Cancer Society, contract 194751-2017.

Variants in SMAD4 or BMPR1A cause juvenile polyposis syndrome, a rare autosomal dominant condition characterized by multiple gastrointestinal hamartomatous polyps. A phenotype of attenuated adenomatous polyposis without hamartomatous polyps is rare.We describe a retrospective cohort of individuals with SMAD4 or BMPR1A heterozygous germline variants, having ≥10 cumulative colorectal adenomas and/or colorectal cancer without hamartomatous polyps. All individuals had multigene panel and duplication/deletion analysis to exclude other genetic syndromes.The study cohort included 8 individuals. The pathogenic potential of the variants was analyzed. Variants detected included 4 missense variants, 1 nonsense variant, 1 splice site variant, and 2 genomic deletions. Features of pathogenicity were present in most variants, and cosegregation of the variant with polyposis or colorectal cancer was obtained in 7 of the 8 families. Three of 8 individuals had colorectal cancer (age less than 50 years) in addition to the polyposis phenotype. Two individuals had extraintestinal neoplasms (pancreas and ampulla of Vater).The clinical phenotype of SMAD4 and BMPR1A variants may infrequently extend beyond the classical juvenile polyposis syndrome phenotype. Applying multigene panel analysis of hereditary cancer-related genes in individuals with unexplained polyposis can provide syndrome-based clinical surveillance for carriers and their family members.

We evaluated whether persistent-positive celiac serology is associated with the risk of hypothyroidism.We extracted a cohort of subjects aged 1-80 years with a positive IgA anti-tissue transglutaminase between January 1, 2008, and December 31, 2012, and a repeat anti-tissue transglutaminase test within 6-36 months from a large population-based electronic medical record database. Based on serology tests, we categorized the pediatric (agelt;21 years) and adult cohorts into normalized or persistent-positive serology groups. All subjects were followed up for incident diagnosis of hypothyroidism from the last serology date up to December 31, 2017. Hazard ratio (HR) along 95% confidence intervals (CIs) were prepared to evaluate the association of celiac serology group with a diagnosis of hypothyroidism, crude, and adjusted for age, sex, and diagnosis of type 1 diabetes mellitus.Among the pediatric cohort (n = 2,687), during a median follow-up of 64 months (interquartile range 48-80), 2.3% (16/681) of the persistent-positive serology group and 1.0% (20/2,006) of the normalized serology group developed hypothyroidism (HR 2.07 [95% CI 1.07-4.44], adjHR 1.77 [95% CI 0.91-3.46]). The rate among the pediatric cohort with an established diagnosis of celiac disease was 3.4% (10/486) vs 1.0% (5/481), HR 2.83 (0.96-8.32). In the adult cohort (n = 1,286), 4.5% (20/442) of the persistent-positive group and 3.9% (33/811) of the normalized serology group developed hypothyroidism (HR 1.13 [95% CI 0.65-1.97]).In this retrospective, age-stratified analysis, we report that persistent-positive serology may be associated with the risk of hypothyroidism among the pediatric population. Prospective cohorts are needed to validate our findings.

(1) Background: Fecal occult blood test (FOBT) is the modality of choice in most countries for colorectal cancer (CRC) screening. We aimed to investigate the risk factors for CRC among patients with a positive FOBT in real life. (2) Methods: This was a retrospective study that included patients who tested positive for FOBT. Data regarding the comorbidities and laboratories were collected and compared between CRC and non-CRC groups. (3) Results: Positive FOBT was found among 45,500 (5.36%) subjects and CRC was found in 1502 (3.3%). CRC patients were older, age 62.7 ± 7.15 years compared with 59.33 ± 7.3 years (p < 0.001), and had significantly higher rates of hypertension (48.4% vs. 44.7%, p = 0.002), iron-deficiency anemia (20.6% vs. 16.4, p < 0.001), family history of CRC (7.3% vs. 5.1%, p < 0.001), and previous CRC (6.5% vs. 0.3%, p < 0.001). Lower levels of hemoglobin, iron, and ferritin were found in the CRC group. Age, family history of CRC, and previous CRC were found to be significant risk factors for diagnosis of CRC after positive FOBT with OR of 1.057, 1.4, and 15.9, respectively. (4) Conclusions: Iron-deficiency anemia, family history of CRC, previous colorectal cancer, and low hemoglobin, iron, and ferritin levels should direct physicians to give high priority to colonoscopy scheduling.