Set2 histone methyltransferase regulates transcription coupled-nucleotide excision repair in yeast.

Helix-distorting DNA lesions, including ultraviolet (UV) light-induced damage, are repaired by the global genomic-nucleotide excision repair (GG-NER) and transcription coupled-nucleotide excision repair (TC-NER) pathways. Previous studies have shown that histone post-translational modifications (PTMs) such as histone acetylation and methylation can promote GG-NER in chromatin. Whether histone PTMs also regulate the repair of DNA lesions by the TC-NER pathway in transcribed DNA is unknown. Here, we report that histone H3 K36 methylation (H3K36me) by the Set2 histone methyltransferase in yeast regulates TC-NER. Mutations in Set2 or H3K36 result in UV sensitivity that is epistatic with Rad26, the primary TC-NER factor in yeast, and cause a defect in the repair of UV damage across the yeast genome. We further show that mutations in Set2 or H3K36 in a GG-NER deficient strain (i.e., rad16Δ) partially rescue its UV sensitivity. Our data indicate that deletion of SET2 rescues UV sensitivity in a GG-NER deficient strain by activating cryptic antisense transcription, so that the non-transcribed strand (NTS) of yeast genes is repaired by TC-NER. These findings indicate that Set2 methylation of H3K36 establishes transcriptional asymmetry in repair by promoting canonical TC-NER of the transcribed strand (TS) and suppressing cryptic TC-NER of the NTS.

Safety and efficacy of direct percutaneous endoscopic jejunostomy tube placement compared with surgical jejunostomy: a tertiary care analysis.

BACKGROUND AND AIMS: Jejunostomy tube placements provides enteral access for feeding in eligible patients who cannot meet their nutritional needs by mouth. They can be surgically placed laparoscopically (lap-J) or with the use of a conventional open laparotomy approach (open-J). Recently, direct percutaneous endoscopic jejunostomy (DPEJ) has emerged as an alternative owing to its low cost and shorter recovery times. We sought to retrospectively compare the procedural success rates and adverse events of these methods. METHODS: Patients were identified by querying our health system patient database and the departmental database of patients who underwent DPEJ. The patients were divided into 3 cohorts based on the procedure: DPEJ, lap-J, or open-J. Patient age and body mass index, procedural success rate, and adverse event rate were compared among the 3 groups. RESULTS: A total of 201 patients met inclusion criteria (65 DPEJ, 111 lap-J, and 25 open-J). Procedural success rates were similar among the 3 groups (DPEJ 96.9%, lap-J 99.1%, open-J 100%; P = .702). Rates of infection and bleeding were also similar among the 3 groups. There were no cases of GI perforation. Tube dysfunction for any reason that required complete removal or replacement within 90 days occurred more often in the surgical groups than in the DPEJ group (DPEJ 0%, lap-J 35.1%, open-J 40.0%; P < .001). This was driven largely by increased rates of tube clogging and tube dislodgement in the surgical groups. CONCLUSIONS: DPEJ is a safe and effective alternative to surgical jejunostomy in eligible patients and may be associated with decreased adverse event rates at 90 days.

Effects of glucagon-like peptide-1 receptor agonists on gastric mucosal visibility and retained gastric contents during EGD.

BACKGROUND AND AIMS: Glucagon-like peptide-1 receptor agonists (GLP-1RAs) are increasingly used in diabetes and obesity management. Although GLP-1RAs delay gastric emptying, their impact on visibility during EGD remains uncertain. METHODS: A 1:1 matched case-control study was conducted. Individuals undergoing EGD who were taking GLP-1RAs were matched to nonusers based on demographic characteristics and diabetes status. A validated scale (POLPREP) was used to determine gastric mucosal visibility scores. RESULTS: A total of 84 pairs (N = 168) were included. GLP-1RA users had significantly lower visibility scores, with a 2.42 times higher likelihood of lower scores compared with nonusers. In addition, GLP-1RA users had a higher incidence of retained gastric contents (13.1% vs 4.8%; adjusted odds ratio, 4.62; P = .025) and aborted procedures due to this issue. No anesthesia-related adverse events were observed. CONCLUSIONS: GLP-1RA use at the time of endoscopy exhibited higher odds of lower gastric mucosal visibility scores, retained contents, and aborted procedures. Further research is warranted.

Performance of Computer-Aided Detection and Quality of Bowel Preparation: A Comprehensive Analysis of Colonoscopy Outcomes.

BACKGROUND: Artificial intelligence (AI) has emerged as a promising tool for detecting and characterizing colorectal polyps during colonoscopy, offering potential enhancements in traditional colonoscopy procedures to improve outcomes in patients with inadequate bowel preparation. AIMS: This study aimed to assess the impact of an AI tool on computer-aided detection (CADe) assistance during colonoscopy in this population. METHODS: This case-control study utilized propensity score matching (PSM) for age, sex, race, and colonoscopy indication to analyze a database of patients who underwent colonoscopy at a single tertiary referral center between 2017 and 2023. Patients were excluded if the procedure was incomplete or aborted owing to poor preparation. The patients were categorized based on the use of AI during colonoscopy. Data on patient demographics and colonoscopy performance metrics were collected. Univariate and multivariate logistic regression models were used to compare the groups. RESULTS: After PSM patients with adequately prepped colonoscopies (n = 1466), the likelihood of detecting hyperplastic polyps (OR = 2.0, 95%CI 1.7-2.5, p < 0.001), adenomas (OR = 1.47, 95%CI 1.19-1.81, p < 0.001), and sessile serrated polyps (OR = 1.90, 95%CI 1.20-3.03, p = 0.007) significantly increased with the inclusion of CADe. In inadequately prepped patients (n = 160), CADe exhibited a more pronounced impact on the polyp detection rate (OR = 4.34, 95%CI 1.6-6.16, p = 0.049) and adenomas (OR = 2.9, 95%CI 2.20-8.57, p < 0.001), with a marginal increase in withdrawal and procedure times. CONCLUSION: This study highlights the significant improvement in detecting diminutive polyps (< 5 mm) and sessile polyps using CADe, although notably, this benefit was only seen in patients with adequate bowel preparation. In conclusion, the integration of AI in colonoscopy, driven by artificial intelligence, promises to significantly enhance lesion detection and diagnosis, revolutionize the procedure's effectiveness, and improve patient outcomes.

Effects of Postactivation Potentiation on Maximal Vertical Jump Performance After a Conditioning Contraction in Upper-Body and Lower-Body Muscle Groups.

ABSTRACT: Downey, RJ, Deprez, DA, and Chilibeck, PD. Effects of postactivation potentiation on maximal vertical jump performance after a conditioning contraction in upper-body and lower-body muscle groups. J Strength Cond Res 36(1): 259-261, 2022-Postactivation potentiation (PAP) involves preperformance contractions that can condition a muscle to enhance subsequent force generation and power output. Our purpose was to examine the effects of conditioning contractions that are specific or nonspecific to the target performance on PAP. Resistance-trained subjects (14 males and 10 females) performed a 7-second isometric contraction involving back squat, bench press (as conditioning contractions), or a control condition (rest) on different days in random order, before maximal vertical jump performance. The back squat as a conditioning contraction increased maximal vertical jump by 1.1 ± 3.0 cm (p < 0.05); however, the bench press as a conditioning contraction unexpectedly reduced maximal vertical jump performance by 1.4 ± 2.7 cm (p < 0.05). Conditioning contractions used to elicit a PAP response should use muscles that are specific to the performance movement. Contractions that are not biomechanically similar to the performance movement may hinder subsequent performance.

Prevalence and Associated Dietary Factors of Rome IV Functional Gastrointestinal Disorders in Rural Western Honduras.

BACKGROUND: The literature is limited regarding the prevalence of functional gastrointestinal disorders (FGIDs) in Central America, and the role of dietary factors. METHODS: The Rome IV diagnostic questionnaire and National Cancer Institute Diet History questionnaire were administered in one-on-one interviews to a distributed cross section of the general adult population of Western Honduras. Our aim was to estimate prevalence of common FGIDs and symptoms and their relationships to dietary habits. RESULTS: In total, 815 subjects were interviewed, of whom 151 fulfilled criteria for an FGID (18.5%). Gastroduodenal FGIDs were noted in 9.4%, with epigastric pain syndrome (EPS) more common than postprandial distress syndrome, 8.5% versus 1.6%. Among bowel disorders, functional abdominal bloating (FAB) was most prevalent (6.3%), followed by irritable bowel syndrome (3.6%), functional diarrhea (FDr; 3.4%), and functional constipation (1.1%). A significant inverse association was noted between regular bean intake and any FGID (OR 0.41, 95% CI 0.27-0.63), driven by IBS and FDr. Vegetable consumption was associated with lower prevalence of functional diarrhea (OR 0.12; 95% CI 0.04-0.35) and any diarrheal disorder (OR 0.11; 95% CI 0.04-0.31). Subjects with a median daily intake of ≥ 4 corn tortillas had 1.75 (95% CI 1.22-2.50) times the odds of having any FGID. CONCLUSIONS: FGIDs were common in this rural low-resource setting in Central America, with an intriguing distribution of specific FGIDs. EPS and FAB were common, but IBS was not. Local dietary factors were associated with specific FGIDs, suggesting that diet may play a role in global variations of FGIDs.

AFM and Raman study of graphene deposited on silicon surfaces nanostructured by ion beam irradiation.

Nanoscale structures were produced on silicon surfaces by low-energy oxygen ion irradiation: periodic rippled or terraced patterns formed spontaneously, depending on the chosen combination of beam incidence angle and ion fluence. Atomic force microscopy image processing and analysis accurately described the obtained nanotopographies. Graphene monolayers grown by chemical vapour deposition were transferred onto the nanostructured silicon surfaces. The interfacial interaction between the textured surface and the deposited graphene governs the conformation of the thin carbon layer; the resulting different degree of regularity and conformality of the substrate-induced graphene corrugations was studied and it was related to the distinctive topographical features of the silicon nanostructures. Raman spectroscopy revealed specific features of the strain caused by the alternating suspension and contact with the underlying nanostructures and the consequent modulation of the silicon-graphene interaction. Lay Description In the field of nanosciences, nanotechnologies and advanced materials, it is pivotal to produce and integrate nanostructures in a controlled, cost-effective and possibly high-throughput manner. Currently, the surface nanopatterning by ion beam irradiation (IBI) is showing its potential in overcoming some of the limits that characterize the conventional lithographic techniques. IBI can produce self-organized and regular patterns of nanostructures, such as ripples, dots, and holes, having heights and lateral periodicities in a pre-defined range. The nanopatterns can develop over large surface areas of a broad class of materials and have been tested for different applications, e.g. microelectronic device fabrication, catalysis, nanoscale magnetism, surface-enhanced Raman scattering. Also, the ion-induced patterns allowed the control of physical properties such as wettability, reflectance, and photoluminescence. As a whole, this is a highly dynamic and continuously evolving field. Graphene was first obtained from bulk graphite by mechanical exfoliation; remarkable mechanical, thermal and optical properties came to light; they make graphene an ideal material for sensing. Also, the research on graphene paves the way for basic and applied studies on other ultrathin thickness materials, such as monolayer transition metal dichalcogenide or monolayer metal oxide, which also show peculiar properties as compared to their bulk version. Since graphene is a zero-gap semi-metal, a finite energy gap must be open to engineer graphene-based electronic devices. At this aim, researchers can take advantage of the mechanical properties of graphene, since its out-of-plane deformation can favourably modify its electronic structure. While the spontaneous, random self-folding of graphene to form wrinkles has thermodynamics reasons and is unavoidable above a certain material length, the interactions between graphene and substrates can generate, in principle, designed wrinkled structures. Therefore, a field of study has emerged, focused on the control and tuning of the geometry of graphene corrugations and their influence on specific physical and chemical properties. To the best of our knowledge, this work studies for the first time the geometry and strain in graphene wrinkles induced by silicon substrates that were suitably nanopatterned by ion beam irradiation.

Incomplete diagnostic follow-up after a positive colorectal cancer screening test: a systematic review.

Background: Colorectal cancer (CRC) screening using faecal occult blood or faecal immunological testing (FOBT/FIT) involves completion of a screening test-then if required a follow-up diagnostic test. Methods: A systematic review, of EMBASE, MEDLINE, the Cochrane Library and Google Scholar, of studies up to 2016. Studies explored characteristics behind, reasons for and interventions to reduce incomplete diagnostic testing after a positive FOBT/FIT in CRC screening. Results: A total of 68 articles were included (63 studies). There is evidence of disparities in uptake by socioeconomic position and ethnicity, as well as geographic remoteness. Positive health beliefs, health knowledge and CRC screening attendance history are associated with increased diagnostic testing. Facets of organised screening, including performance feedback and funding improve follow-up-whilst guidelines increase diagnostic testing and reduce inappropriate exclusions. Between 2 and 11% of participants refuse follow-up, with perception of pain critical. Interventions, notably a screening specialist to aid the patient journey, as well as tracking and reminder systems, can increase diagnostic testing. Conclusions: Although rates of non-attendance in those eligible are low, this represents a group with health care need. Disparities must be eliminated to alleviate wider health inequity. Organised, screening can reduce incomplete diagnostic testing, as can accessible health information.

De novo intracerebral arteriovenous malformations and a review of the theories of their formation.

PURPOSE: Arteriovenous malformations (AVM) are still frequently described as congenital lesions in medical texts despite little evidence existing for their congenital nature. Increasing numbers of case reports of de novo AVMs add weight to the notion that they are dynamic lesions and that they can form postnatally. A thorough review of all reported cases of de novo AVM formation and a review of articles relating to AVM pathogenesis was planned to summarise current research on AVM pathogenesis and provide insight into the future implications for AVM research and treatment. METHODS AND RESULTS: MEDLINE was searched to find 29 cases of de novo AVM formation with prior MRI imaging, nine of which also had prior digital subtraction angiography. A discussion of AVM pathogenesis is undertaken through a review of articles relating to AVM embryology, postnatal angiogenesis, syndromic forms of AVMs and studies of AVM molecular biology and genetics in human and animal models. CONCLUSIONS: There is little evidence for an embryological origin through dysregulated vasculogenesis, whereas there is a raft of evidence to support dysregulated angiogenesis in childhood or even adulthood. Translational implications include risk stratification by biomarkers for predicting haemorrhage and novel therapeutic approaches to suppress AVM proliferation and initiate reversal.

Semiquantitative Volumetry by Sequential PET/CT May Improve Prediction of Complete Response to Neoadjuvant Chemoradiation in Patients With Distal Rectal Cancer.

BACKGROUND: Previous studies using PET/CT imaging have failed to accurately identify complete responders to neoadjuvant chemoradiation among patients with rectal cancer. The use of metabolic parameters alone or imprecise delineation of baseline and residual tumor volumes may have contributed for these disappointing findings. OBJECTIVE: The purpose of this study was to determine the accuracy of complete response identification in rectal cancer after neoadjuvant chemoradiation by sequential PET/CT imaging with a decrease in tumor metabolism and volume using optimal tumor volume delineation. DESIGN: This was a retrospective comparison of prospectively collected data from a clinical trial (National Clinical Trial 00254683). SETTINGS: The study was conducted at a single research center. PATIENTS: Ninety patients with cT2-4N0-2M0 distal rectal cancer underwent sequential PET/CT at baseline and 12 weeks after neoadjuvant chemoradiation. Quantitative metabolic analysis (median and maximal standard uptake values), volumetric estimates (metabolic tumor volume), and composite estimates incorporating volume and quantitative data (total lesion glycolysis) were compared for the assessment of response to neoadjuvant chemoradiation using receiver operating characteristic curves. Individual standard uptake value thresholds were used according to response to neoadjuvant chemoradiation to match metabolic activity and optimize volume delineation. MAIN OUTCOME MEASURES: The accuracy of complete response identification by multiple volumetric and metabolic parameters using sequential PET/CT imaging was measured. RESULTS: Variation in total lesion glycolysis between baseline and 12-week PET/CT scans was associated with the best area under the curve (area under the curve = 0.81 (95% CI, 0.69-0.92)) when compared with standard uptake value or metabolic tumor volume for the identification of a complete responder. Patients with a ≥92% decrease in total lesion glycolysis between baseline and 12-week PET/CT scan had a 90% chance to harbor complete response. LIMITATIONS: This study was limited by its lack of interobserver agreement analysis. CONCLUSIONS: PET/CT scan using volume and metabolic estimates with individual standard uptake value thresholds for volume determination may provide a useful tool to predict response to neoadjuvant chemoradiation in distal rectal cancer.

The documentation of consent and disclosure of neurogenetic testing outside clinical genetics.

Neurogenetic tests are increasingly requested by clinical neurologists without any formal training in clinical genetics. The aim of our study was to assess the documentation of consent and disclosure of genetic test results in a large regional clinical neuroscience centre. Documentation of some form of consent was evident in only 26/132 (20 %) of tests. However, the higher proportion of both positive and negative results disclosed (50/132, 38 %) suggest that the former figure may underestimate actual rates of undocumented consent within the clinical setting. Our findings highlight the need for a review of established practices surrounding consent in clinical neurology.

Colorectal Cancer Screening Programs in Latin America: A Systematic Review and Meta-Analysis.

Importance: Colorectal cancer (CRC) is a leading cause of cancer-related mortality globally, with increasing incidence and mortality in Latin America. CRC screening programs can reduce disease burden, but information on screening programs in Latin America is limited. Objective: To describe characteristics (eg, type of program, uptake, neoplastic yield) of CRC screening programs in Latin America. Data Sources: PubMed, Ovid MEDLINE, EMBASE, Cochrane, PsycINFO, Web of Science Core Collection, LILACS, and SciELO were searched from inception to February 2023. Relevant references from bibliographies, conference proceedings, and gray literature were considered. The search strategy included English, Spanish, and Portuguese terms. Study Selection: Included were studies of CRC screening programs in Latin America using fecal immunochemical test (FIT) or colonoscopy as the primary screening method. Four reviewers independently assessed study eligibility based on titles, with review of abstracts and full texts as needed. Data Extraction and Synthesis: Guidelines from Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) were followed for data abstraction and quality assessment. Descriptive information was extracted, and data were pooled using a random-effects model. Main outcomes and Measures: Program performance indicators included rates of participation and FIT positivity, adenoma detection rate (ADR), advanced adenoma detection rate (AADR), CRC detection rate, and colonoscopy quality indicators. Results: There were 17 studies included from upper middle-income and high-income countries in Latin America with a total of 123 929 participants. Thirteen studies used FIT as the initial screening method, whereas 4 used screening colonoscopy. The participation rate in FIT-based programs was 85.8% (95% CI, 78.5%-91.4%). FIT positivity rates were 15.2% (95% CI, 9.6%-21.8%) for the 50-ng/mL threshold and 9.7% (95% CI, 6.8%-13.0%) for the 100-ng/mL threshold. For FIT-based studies, the pooled ADR was 39.0% (95% CI, 29.3%-49.2%) and CRC detection rate was 4.9% (95% CI, 2.6%-7.9%); for screening colonoscopy-based studies, the pooled ADR was 19.9% (95% CI, 15.5%-24.8%) and CRC detection rate was 0.4% (95% CI, 0.1%-0.8%). Conclusions and Relevance: This systematic review and meta-analysis suggests that CRC screening in upper middle-income countries in Latin America is feasible, detecting rates of neoplasia comparable with those of high-income regions. Population-based screening programs should be developed or enhanced in these settings. There is a knowledge gap regarding feasibility and yield of screening programs in lower middle-income countries.

Cognitive Impairment and Insomnia in Celiac Disease: A Systematic Review and Meta-Analysis.

Emerging evidence suggests a broader spectrum of celiac disease (CeD) system involvement, including neurological manifestations. We aimed to conduct a systematic review and meta-analysis of the available evidence from studies assessing the association of cognitive impairment and insomnia with CeD. A total of 259 participants with CeD were included in the studies investigating insomnia and 179 were included in studies investigating cognitive impairment. The overall pooled odds ratio for insomnia in patients with CeD was 1.83 (95% confidence interval, 1.38 to 2.42; I2=0.00%). The present study provides valuable insights into the available evidence from studies investigating cognitive impairment in patients with CeD and our systematic review and metaanalysis revealed a significant association between CeD and insomnia.

Vertical heterostructure of graphite-MoS2 for gas sensing.

2D materials, given their form-factor, high surface-to-volume ratio, and chemical functionality have immense use in sensor design. Engineering 2D heterostructures can result in robust combinations of desirable properties but sensor design methodologies require careful considerations about material properties and orientation to maximize sensor response. This study introduces a sensor approach that combines the excellent electrical transport and transduction properties of graphite film with chemical reactivity derived from the edge sites of semiconducting molybdenum disulfide (MoS2) through a two-step chemical vapour deposition method. The resulting vertical heterostructure shows potential for high-performance hybrid chemiresistors for gas sensing. This architecture offers active sensing edge sites across the MoS2 flakes. We detail the growth of vertically oriented MoS2 over a nanoscale graphite film (NGF) cross-section, enhancing the adsorption of analytes such as NO2, NH3, and water vapor. Raman spectroscopy, density functional theory calculations and scanning probe methods elucidate the influence of chemical doping by distinguishing the role of MoS2 edge sites relative to the basal plane. High-resolution imaging techniques confirm the controlled growth of highly crystalline hybrid structures. The MoS2/NGF hybrid structure exhibits exceptional chemiresistive responses at both room and elevated temperatures compared to bare graphitic layers. Quantitative analysis reveals that the sensitivity of this hybrid sensor surpasses other 2D material hybrids, particularly in parts per billion concentrations.

Population-based Study of Gastric Cancer Survival and Associations in Rural Western Honduras.

BACKGROUND: Two-thirds of global cancer occur in low/middle income countries (LMICs). Northern Central America is the largest LMIC region in the western hemisphere, and lack cancer registries to guide cancer control. We conducted a gastric cancer (GC) survival study in rural western Honduras, characterized as having among the highest GC incidence rates in Latin America. METHODS: The cohort of incident GC diagnosed between 2002-2015 was studied with active follow-up, with household visits. The regional gastric cancer registry was primary for case identification, with completeness examination with hospital data and national death certificates. Cox regression models were used for survival calculations. RESULTS: Survival follow-up was achieved in 741/774 patients (95.7%). Household interviews were conducted in 74.1% (n=549). 65.7% were male, median age at diagnosis was 64 years, 24.5% were <55. 43.9% of tumors had pyloric obstruction. 45.2%, 43.2%, and 7.3% of histology was intestinal, diffuse, and mixed, respectively. 24.7% patients received treatment. 5-year survival rates were 9.9% for both males and females, 7.7% for age <45, and 7.9% for diffuse GC. Median survival time was 4.8 months (95%CI,4.2-5.6). In the final Cox regression model including age, sex, Lauren subtype, and poverty index, only treatment was significantly associated with survival (HR 2.43, 95%CI,1.8-3.2). CONCLUSIONS: Markedly low gastric cancer 5-year survival rates are observed in rural Central America. The majority of patients present with advanced disease, and a minority have access to therapy. IMPACT: The findings have implications for cancer control in the Central America LMICs and for U.S. Latino populations.

High Incidence of Gastric Cancer in El Salvador: A National Multisectorial Study 2000-2014.

BACKGROUND: Gastric adenocarcinoma (GC) is the fourth leading cause of global cancer mortality, and leading infection-associated cancer. GC has significant geographic variability, with a high incidence in East Asia and mountainous regions of Latin America. In the U.S., GC represents a marked disparity with incidence rates that are 2-3 times higher in Hispanics compared to non-Hispanic whites. METHODS: We conducted a national retrospective study of incident GC in El Salvador from to 2000-2014 to estimate the age-standardized incidence rate (ASIR) by using a combination of pathology and endoscopy databases. A unique multisectorial coalition was formed between the Ministry of Health (MINSAL) and ES Gastroenterology Society (AGEDES), representing public hospitals (n=5), governmental employee hospitals (ISSS, n=5), and private facilities (n=6), accounting for >95% of national endoscopy capacity. HER2 and EBV tumor status was ascertained in a representative sample during 2014-2016. RESULTS: 10,039 unique cases of GC were identified, 45.5% female, and mean age of 65. 21% and 9.4% were <55 and <45 years old, respectively. ASIRs (M, F) were 18.9 (95%CI;14.4-20.7) and 12.2 per 100,000 persons (95%CI;10.9-13.5), respectively, in the period 2010-2014 with all centers operational. Intestinal GC was 2.8 times more common than diffuse GC. 23.2% had partial or complete pyloric obstruction. The HER2 2+/3+ status was 16.7% and EBER positivity was 10.2%. CONCLUSIONS: A high incidence of gastric cancer was confirmed in El Salvador, and nearly half of patients were female. IMPACT: The findings have implications for cancer control in the Central America LMICs and for U.S. Latino populations.

Establishment of a Mesoamerican-Caribbean south-south research platform: Challenges in the Meriva (curcuminoids) Gastric Cancer Chemoprevention Trial.

Gastric adenocarcinoma (GAC) is the fourth-leading global cause of cancer mortality and leading infection-associated cancer. High incidence regions include Latin America and Eastern Asia. Immigrants from high incidence regions maintain their GAC risk. GAC is a major U.S. cancer disparity, incidence rates are 2-10 time higher in non-white populations. Emerging guidelines recommend 3-year surveillance endoscopy for patients with high-risk gastric premalignant conditions (GPMCs). Clinical trials of GPMC chemoprevention agents are lacking. We conducted an NCI Division of Cancer Prevention-funded, phase II placebo-controlled chemoprevention trial in patients with GPMCs (atrophic gastritis, intestinal metaplasia) with a highly bioavailable preparation of curcuminoids (Meriva®). The trial sites in Puerto Rico and rural Honduras had important characteristics: (1) representative Caribbean and Mesoamerican populations, linked to large U.S. immigrant populations; (2) high prevalence of H. pylori infection and GPMCs; (3) absence of turmeric and curcuminoids in the local diets; (4) proven bidirectional collaboration with U.S. academic institutions. H. pylori-negative GPMC patients were randomized to study drug (500 mg po bid) or placebo for 180 days (NCT02782949), with primary outcomes based upon histologic parameters. Principal study challenges included: (1) international regulatory environment; (2) research infrastructure strengthening, particularly in Central America; (3) participant recruitment in Honduras wherein only 10-15% are H. pylori negative; (4) the Covid-19 pandemic; and (5) natural disasters (3 hurricanes). There were no losses to follow-up related to the pandemic or natural disasters. In conclusion, the south-south partnership provides a model for chemoprevention and translational studies in Latino populations with prevalent cancers such as GAC.

Prevalence of celiac disease in systemic lupus erythematosus, sjogren syndrome and systemic sclerosis: A systematic review and meta-analysis.

BACKGROUND: Celiac disease (CeD) is an immune-mediated disorder affecting the small bowel, associated with genetic factors and increasing global prevalence. AIM: This study explores the association between CeD, Systemic Lupus Erythematosus (SLE), primary Sjogren syndrome (pSS), and Systemic Sclerosis (SSc). METHODS: A systematic review and meta-analysis were conducted following PRISMA guidelines. Searches across multiple databases yielded 2728 articles, with 15 studies selected. Data extraction included study characteristics, prevalence of CeD and CeD antibodies in SLE, pSS, and SSc. Quality assessment utilized the Newcastle-Ottawa Scale. RESULTS: The meta-analysis revealed a pooled prevalence of biopsy-proven CeD in SLE, pSS, and SSc of approximately 3%. Seroprevalence of any CeD antibody in SLE, pSS, and SSc ranged from 3% to 10%. Notably, pSS exhibited the highest prevalence at 5.59%. High heterogeneity was observed in seroprevalence across autoimmune conditions. Quality assessment indicated robust methodological quality in the selected studies. CONCLUSION: This study highlights a significantly higher prevalence of CeD, especially pSS, compared to the general population. The findings underscore the importance of recognizing elevated CeD antibodies in patients with SLE, pSS and SSc emphasizing the need for early detection and comprehensive care for gastrointestinal symptoms in these conditions.

High Gastric Cancer Mortality and Years of Life Lost in Nicaragua: A Population-Based Study 1997 - 2012.

BACKGROUND: Gastric adenocarcinoma (GC) is the fourth leading cause of cancer-related mortality, and leading infection-associated cancer. GC has striking geographic variability, with high incidence in East Asia and mountainous Latin America. Reliable cancer data and population-based cancer registries (PBCRs) are lacking for the majority of LMICs, including the Central American Four region (CA-4, Nicaragua, El Salvador, Honduras, and Guatemala). METHODS: Mortality data for Nicaragua were obtained from the highly-rated Ministry of Health death registry. All the patients were diagnosed with gastric cancer between 1997 and 2012 (ICD-10 codes C16.0-C16.9) and death due to any cause were included in the study. Data on variables such as sex, age (stratified by 5-year age groups), municipality, urban/rural, altitude, and year of death were analyzed. RESULTS: A total of 3,886 stomach cancer deaths were reported in Nicaragua between 1997 and 2012, of which 2,214 (56.9%) were male. The ASMR were 13.1 and 8.7 per 100,000 habitants for males and females, respectively, and without significant change during the study period (APC= -0.7, P=0.2). An average of 17.9 years were lost per death (AYLL), accounting for 67,964 years of life lost (YYL). CONCLUSIONS: The burden of gastric cancer mortality is high in Nicaragua with significantly elevated ASMR, YYL, and AYLL. IMPACT: The projected increase in mortality portends the double cancer burden in northern Central America, with persistent infection-associated cancers and growing transition cancers (e.g., breast and colon cancers), which has implications for cancer control in Mesoamerica and U.S. Latino populations.