Publications by authors named "Andres Cardenas"

219 Publications

Hyperkalemia in patients with cirrhosis and ACLF.

Dig Liver Dis 2021 Apr 23. Epub 2021 Apr 23.

GI/Liver Unit Hospital Clinic, Barcelona, Spain; Institut d'Investigacions Biomediques August Pi I Sunyer (IDIBAPS) y Centro de Investigaciones en Red Hepaticas y Digestivas (CIBERehd), Spain; Faculty of Medicine, University of Barcelona, Villarroel 170, Esc 3-2, Barcelona 08036, Spain. Electronic address:

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http://dx.doi.org/10.1016/j.dld.2021.03.018DOI Listing
April 2021

Residential PM exposure and the nasal methylome in children.

Environ Int 2021 Apr 16;153:106505. Epub 2021 Apr 16.

Department of Environmental Health, Harvard T. H. Chan School of Public Health, Boston, MA, USA; Channing Division of Network Medicine and Division of Pulmonary and Critical Care Medicine, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA. Electronic address:

Rationale: PMinduced adverse effects on respiratory health may be driven by epigenetic modifications in airway cells. The potential impact of exposure duration on epigenetic alterations in the airways is not yet known.

Objectives: We aimed to study associations of fine particulate matter PM exposure with DNA methylation in nasal cells.

Methods: We conducted nasal epigenome-wide association analyses within 503 children from Project Viva (mean age 12.9 y), and examined various exposure durations (1-day, 1-week, 1-month, 3-months and 1-year) prior to nasal sampling. We used residential addresses to estimate average daily PM at 1 km resolution. We collected nasal swabs from the anterior nares and measured DNA methylation (DNAm) using the Illumina MethylationEPIC BeadChip. We tested 719,075 high quality autosomal CpGs using CpG-by-CpG and regional DNAm analyses controlling for multiple comparisons, and adjusted for maternal education, household smokers, child sex, race/ethnicity, BMI z-score, age, season at sample collection and cell-type heterogeneity. We further corrected for bias and genomic inflation. We tested for replication in a cohort from the Netherlands (PIAMA).

Results: In adjusted analyses, we found 362 CpGs associated with 1-year PM (FDR < 0.05), 20 CpGs passing Bonferroni correction (P < 7.0x10) and 10 Differentially Methylated Regions (DMRs). In 445 PIAMA participants (mean age 16.3 years) 11 of 203 available CpGs replicated at P < 0.05. We observed differential DNAm at/near genes implicated in cell cycle, immune and inflammatory responses. There were no CpGs or regions associated with PM levels at 1-day, 1-week, or 1-month prior to sample collection, although 2 CpGs were associated with past 3-month PM.

Conclusion: We observed wide-spread DNAm variability associated with average past year PM exposure but we did not detect associations with shorter-term exposure. Our results suggest that nasal DNAm marks reflect chronic air pollution exposure.
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http://dx.doi.org/10.1016/j.envint.2021.106505DOI Listing
April 2021

Controlled human exposures to diesel exhaust: a human epigenome-wide experiment of target bronchial epithelial cells.

Environ Epigenet 2021 9;7(1):dvab003. Epub 2021 Apr 9.

Department of Statistics, Faculty of Arts and Sciences, Harvard University, Cambridge, MA 02138, USA.

Diesel exhaust (DE) is a major contributor to ambient air pollution around the world. It is a known human carcinogen that targets the respiratory system and increases risk for many diseases, but there is limited research on the effects of DE exposure on the epigenome of human bronchial epithelial cells. Understanding the epigenetic impact of this environmental pollutant can elucidate biological mechanisms involved in the pathogenesis of harmful DE-related health effects. To estimate the causal effect of short-term DE exposure on the bronchial epithelial epigenome, we conducted a controlled single-blinded randomized crossover human experiment of exposure to DE and used bronchoscopy and Illumina 450K arrays for data collection and analysis, respectively. Of the 13 participants, 11 (85%) were male and 2 (15%) were female, and 12 (92%) were White and one (8%) was Hispanic; the mean age was 26 years (SD = 3.8 years). Eighty CpGs were differentially methylated, achieving the minimum possible exact -value of =2.44 × 10 ( 2/2). In regional analyses, we found two differentially methylated regions (DMRs) annotated to the chromosome 5 open reading frame 63 genes (; 7-CpGs) and unc-45 myosin chaperone A gene (; 5-CpGs). Both DMRs showed increased DNA methylation after DE exposure. The average causal effects for the DMRs ranged from 1.5% to 6.0% increases in DNA methylation at individual CpGs. In conclusion, we found that short-term DE alters DNA methylation of genes in target bronchial epithelial cells, demonstrating epigenetic level effects of exposure that could be implicated in pulmonary pathologies.
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http://dx.doi.org/10.1093/eep/dvab003DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8035831PMC
April 2021

Complications of Cirrhosis.

Clin Liver Dis 2021 May 10;25(2):xiii-xiv. Epub 2021 Mar 10.

Universitätsklinikum AKH Wien, Gastroenterology Office 7I Red Tower, Währinger Gürtel 18-20, A-1090 Vienna, Austria. Electronic address:

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http://dx.doi.org/10.1016/j.cld.2021.02.002DOI Listing
May 2021

Invasive Procedures in Patients with Cirrhosis: A Clinical Approach Based on Current Evidence.

Clin Liver Dis 2021 May 10;25(2):461-470. Epub 2021 Mar 10.

Institut d'Investigacions Biomèdiques August Pi-Sunyer (IDIBAPS) and Ciber de Enfermedades Hepáticas y Digestivas (CIBEREHD), Barcelona, Spain; GI/Liver Unit, Institut Clínic de Malalties Digestives i Metabòliques, Hospital Clínic, Barcelona, Spain; Department of Medicine, University of Barcelona, Spain. Electronic address:

The aim on of this article is to provide an update on the coagulation disturbances of patients with cirrhosis. It summarizes basic concepts of coagulation in cirrhosis, available tests used to predict bleeding, procedures and risk of bleeding, and the rationale and expert-based recommendations of prophylactic measures for patients with cirrhosis who undergo invasive procedures.
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http://dx.doi.org/10.1016/j.cld.2021.02.001DOI Listing
May 2021

Effect of Addition of Dimethyl Sulfoxide to Simplified Adhesives on Dentin Bond Durability after Three Years of Water Storage.

J Adhes Dent 2021 Apr;23(2):159-165

Purpose: To evaluate the effect of inclusion of two dimethyl sulfoxide (DMSO) concentrations in simplified etch-and-rinse adhesives on dentin bonding durability after three years of water storage.

Materials And Methods: Forty-two caries-free third molars were divided into six experimental groups (n = 7) according to the following factors: 1) adhesive (Adper Single Bond 2 [SB], 3M Oral Care; Prime&Bond 2.1 [PB], Dentsply Sirona); 2) concentration of DMSO (control group: 0.0% DMSO; addition of 0.2% DMSO [0.2] and 2% DMSO [2.0]). After completing restoration, specimens were stored in water (37°C) for 24 h, sectioned into adhesive-dentin sticks (0.8 mm2), tested for microtensile bond strength (µTBS) at 0.5 mm/min, and examined for nanoleakage (NL) using SEM immediately thereafter or after three years of water storage. Data were subjected to a three-way repeated-measures ANOVA and Tukey's test (α = 0.05) for each property evaluated.

Results: After three years of water storage, for both adhesives, the incorporation of 2% DMSO maintained the µTBS when compared to immediate µTBS (p > 0.05). In general, SB resulted in a statistically significantly higher mean of µTBS compared to PB, independent of the DMSO concentration after water storage (p < 0.05). Furthermore, the amount of NL was lower and practically limited to the hybrid layer given the concentrations of 0.2% and 2% DMSO for both tested adhesives after three years.

Conclusion: The incorporation of DMSO in simplified etch-and-rinse adhesives maintains the long-term stability of the dentin bond.
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http://dx.doi.org/10.3290/j.jad.b1079585DOI Listing
April 2021

Adopting a "Compound" Exposome Approach in Environmental Aging Biomarker Research: A Call to Action for Advancing Racial Health Equity.

Environ Health Perspect 2021 04 6;129(4):45001. Epub 2021 Apr 6.

Division of Community Health Sciences, School of Public Health, University of Illinois at Chicago, Chicago, Illinois, USA.

Background: In June 2020, the National Academies of Sciences, Engineering, and Medicine hosted a virtual workshop focused on integrating the science of aging and environmental health research. The concurrent COVID-19 pandemic and national attention on racism exposed shortcomings in the environmental research field's conceptualization and methodological use of race, which have subsequently hindered the ability of research to address racial health disparities. By the workshop's conclusion, the authors deduced that the utility of environmental aging biomarkers-aging biomarkers shown to be specifically influenced by environmental exposures-would be greatly diminished if these biomarkers are developed absent of considerations of broader societal factors-like structural racism-that impinge on racial health equity.

Objectives: The authors reached a post-workshop consensus recommendation: To advance racial health equity, a "compound" exposome approach should be widely adopted in environmental aging biomarker research. We present this recommendation here.

Discussion: The authors believe that without explicit considerations of racial health equity, people in most need of the benefits afforded by a better understanding of the relationships between exposures and aging will be the least likely to receive them because biomarkers may not encompass cumulative impacts from their unique social and environmental stressors. Employing an exposome approach that allows for more comprehensive exposure-disease pathway characterization across broad domains, including the social exposome and neighborhood factors, is the first step. Exposome-centered study designs must then be supported with efforts aimed at increasing the recruitment and retention of racially diverse study populations and researchers and further "compounded" with strategies directed at improving the use and interpretation of race throughout the publication and dissemination process. This compound exposome approach maximizes the ability of our science to identify environmental aging biomarkers that explicate racial disparities in health and best positions the environmental research community to contribute to the elimination of racial health disparities. https://doi.org/10.1289/EHP8392.
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http://dx.doi.org/10.1289/EHP8392DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8043128PMC
April 2021

Associations of DNA Methylation Mortality Risk Markers with Congenital Microcephaly from Zika Virus: A Study of Brazilian Children Less than 4 Years of Age.

J Trop Pediatr 2021 Jan;67(1)

Division of Environmental Health Sciences, School of Public Health and Center for Computational Biology, University of California, Berkeley, CA, USA Berkeley.

Background: Zika virus (ZIKV)-associated congenital microcephaly is an important contributor to pediatric death, and more robust pediatric mortality risk metrics are needed to help guide life plans and clinical decision making for these patients. Although common etiologies of pediatric and adult mortality differ, early life health can impact adult outcomes-potentially through DNA methylation. Hence, in this pilot study, we take an early step in identifying pediatric mortality risk metrics by examining associations of ZIKV infection and associated congenital microcephaly with existing adult DNA methylation-based mortality biomarkers: GrimAge and Zhang's mortality score (ZMS).

Methods: Mortality measures were calculated from previously published HumanMethylationEPIC BeadChip data from 44 Brazilian children aged 5-40 months (18 with ZIKV-associated microcephaly; 7 normocephalic, exposed to ZIKV in utero; and 19 unexposed controls). We used linear models adjusted for chronological age, sex, methylation batch and white blood cell proportions to evaluate ZIKV and mortality marker relationships.

Results: We observed significant decreases in GrimAge-component plasminogen activator inhibitor-1 [PAI-1; β = -2453.06 pg/ml, 95% confidence interval (CI) -3652.96, -1253.16, p = 0.0002], and ZMS-site cg14975410 methylation (β = -0.06, 95% CI -0.09, -0.03, p = 0.0003) among children with microcephaly compared to controls. PAI-1 (β = -2448.70 pg/ml, 95% CI -4384.45, -512.95, p = 0.01) and cg14975410 (β = 0.01, 95% CI -0.04, 0.06, p = 0.64) results in comparisons of normocephalic, ZIKV-exposed children to controls were not statistically significant.

Conclusion: Our results suggest that elements of previously-identified adult epigenetic markers of mortality risk are associated with ZIKV-associated microcephaly, a known contributor to pediatric mortality risk. These findings may provide insights for efforts aimed at developing pediatric mortality markers.
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http://dx.doi.org/10.1093/tropej/fmab020DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8022928PMC
January 2021

DNA methylation architecture of the ACE2 gene in nasal cells of children.

Sci Rep 2021 03 29;11(1):7107. Epub 2021 Mar 29.

Division of Chronic Disease Research Across the Lifecourse, Department of Population Medicine, Harvard Medical School and Harvard Pilgrim Health Care Institute, Boston, MA, USA.

Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) has led to the global coronavirus disease 2019 (COVID-19) pandemic. SARS-CoV-2 enters cells via angiotensin-Converting Enzyme 2 (ACE2) receptors, highly expressed in nasal epithelium with parallel high infectivity. The nasal epigenome is in direct contact with the environment and could explain COVID-19 disparities by reflecting social and environmental influences on ACE2 regulation. We collected nasal swabs from anterior nares of 547 children, measured DNA methylation (DNAm), and tested differences at 15 ACE2 CpGs by sex, age, race/ethnicity and epigenetic age. ACE2 CpGs were differentially methylated by sex with 12 sites having lower DNAm (mean = 12.71%) and 3 sites greater DNAm (mean = 1.45%) among females relative to males. We observed differential DNAm at 5 CpGs for Hispanic females (mean absolute difference = 3.22%) and lower DNAm at 8 CpGs for Black males (mean absolute difference = 1.33%), relative to white participants. Longer DNAm telomere length was associated with greater ACE2 DNAm at 11 and 13 CpGs among males (mean absolute difference = 7.86%) and females (mean absolute difference = 8.21%), respectively. Nasal ACE2 DNAm differences could contribute to our understanding COVID-19 severity and disparities reflecting upstream environmental and social influences. Findings need to be confirmed among adults and patients with risk factors for COVID-19 severity.
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http://dx.doi.org/10.1038/s41598-021-86494-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8007733PMC
March 2021

Exposure to violence, chronic stress, nasal DNA methylation, and atopic asthma in children.

Pediatr Pulmonol 2021 Mar 22. Epub 2021 Mar 22.

Division of Pediatric Pulmonary Medicine, UPMC Children's Hospital of Pittsburgh, University of Pittsburgh, Pittsburgh, Pennsylvania, USA.

Background: Exposure to violence (ETV) or chronic stress may influence asthma through unclear mechanisms.

Methods: Epigenome-wide association study (EWAS) of ETV or chronic stress measures and DNA methylation in nasal epithelium from 487 Puerto Ricans aged 9-20 years who participated in the Epigenetic Variation and Childhood Asthma in Puerto Ricans study [EVA-PR]). We assessed four measures of ETV and chronic stress in children (ETV scale, gun violence, and perceived stress) and their mothers (perceived stress). Each EWAS was conducted using linear regression, with CpGs as dependent variables and the stress/violence measure as a predictor, adjusting for age, sex, the top five principal components, and SVA latent factors. We then selected the top 100 CpGs (by p value) associated with each stress/violence measure in EVA-PR and conducted a meta-analysis of the selected CpGs and atopic asthma using data from EVA-PR and two additional cohorts (Project Viva and PIAMA).

Results: Three CpGs (in SNN, PTPRN2, and LINC01164) were associated with maternal perceived stress or gun violence (p = 1.28-3.36 × 10 ), but not with atopic asthma, in EVA-PR. In a meta-analysis of three cohorts, which included the top CpGs associated with stress/violence measures in EVA-PR, 12 CpGs (in STARD3NL, SLC35F4, TSR3, CDC42SE2, KLHL25, PLCB1, BUD13, OR2B3, GALR1, TMEM196, TEAD4, and ANAPC13) were associated with atopic asthma at FDR-p < .05.

Conclusions: Pending confirmation in longitudinal studies, our findings suggest that nasal epithelial methylation markers associated with measures of ETV and chronic stress may be linked to atopic asthma in children and adolescents.
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http://dx.doi.org/10.1002/ppul.25372DOI Listing
March 2021

Comparative epigenome-wide analysis highlights placenta-specific differentially methylated regions.

Epigenomics 2021 Mar 4;13(5):357-368. Epub 2021 Mar 4.

Département de Biologie, Université de Sherbrooke, Sherbrooke, Québec, J1K 2R1, Canada.

The placenta undergoes DNA methylation (DNAm) programming that is unique compared with all other fetal tissues. We aim to decipher some of the physiologic roles of the placenta by comparing its DNAm profile with that of another fetal tissue. We performed a comparative analysis of genome-wide DNAm of 444 placentas paired with cord blood samples collected at birth. Gene ontology term analyses were conducted on the resulting differentially methylated regions. Genomic regions upstream of transcription start sites showing lower DNAm in the placenta were enriched with terms related to miRNA functions and genes encoding G-protein-coupled receptors. These results highlight genomic regions that are differentially methylated in the placenta in contrast to fetal blood.
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http://dx.doi.org/10.2217/epi-2020-0271DOI Listing
March 2021

Detecting differentially methylated regions with multiple distinct associations.

Epigenomics 2021 Mar 1;13(6):451-464. Epub 2021 Mar 1.

Department of Biostatistics, Boston University School of Public Health, Boston, MA, 02118, USA.

We evaluated five methods for detecting differentially methylated regions (DMRs): DMRcate, comb-p, seqlm, GlobalP and dmrff. We used a simulation study and real data analysis to evaluate performance. Additionally, we evaluated the use of an ancestry-matched reference cohort to estimate correlations between CpG sites in cord blood. Several methods had inflated Type I error, which increased at more stringent significant levels. In power simulations with 1-2 causal CpG sites with the same direction of effect, dmrff was consistently among the most powerful methods. This study illustrates the need for more thorough simulation studies when evaluating novel methods. More work must be done to develop methods with well-controlled Type I error that do not require individual-level data.
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http://dx.doi.org/10.2217/epi-2020-0344DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8023344PMC
March 2021

Per- and polyfluoroalkyl substances and calcifications of the coronary and aortic arteries in adults with prediabetes: Results from the diabetes prevention program outcomes study.

Environ Int 2021 06 22;151:106446. Epub 2021 Feb 22.

Division of Chronic Disease Research Across the Lifecourse, Department of Population Medicine, Harvard Medical School and Harvard Pilgrim Health Care Institute, Boston, MA, USA.

Background: Per- and polyfluoroalkyl substances (PFAS) are endocrine disrupting chemicals that have been associated with cardiovascular risk factors including elevated body weight and hypercholesterolemia. Therefore, PFAS may contribute to the development of atherosclerosis and cardiovascular disease (CVD). However, no previous study has evaluated associations between PFAS exposure and arterial calcification.

Methods And Results: This study used data from 666 prediabetic adults enrolled in the Diabetes Prevention Program trial who had six PFAS quantified in plasma at baseline and two years after randomization, as well as measurements of coronary artery calcium (CAC) and ascending (AsAC) and descending (DAC) thoracic aortic calcification 13-14 years after baseline. We performed multinomial regression to test associations between PFAS and CAC categorized according to Agatston score [low (<10), moderate (11-400) and severe (>400)]. We used logistic regression to assess associations between PFAS and presence of AsAC and DAC. We adjusted models for baseline sex, age, BMI, race/ethnicity, cigarette smoking, education, treatment assignment (placebo or lifestyle intervention), and statin use. PFAS concentrations were similar to national means; 53.9% of participants had CAC > 11, 7.7% had AsAC, and 42.6% had DAC. Each doubling of the mean sum of plasma concentrations of linear and branched isomers of perfluorooctane sulfonic acid (PFOS) was associated with 1.49-fold greater odds (95% CI: 1.01, 2.21) of severe versus low CAC. This association was driven mainly by the linear (n-PFOS) isomer [1.54 (95% CI: 1.05, 2.25) greater odds of severe versus low CAC]. Each doubling of mean plasma N-ethyl-perfluorooctane sulfonamido acetic acid concentration was associated with greater odds of CAC in a dose-dependent manner [OR = 1.26 (95% CI:1.08, 1.47) for moderate CAC and OR = 1.37 (95% CI:1.07, 1.74) for severe CAC, compared to low CAC)]. Mean plasma PFOS and n-PFOS were also associated with greater odds of AsAC [OR = 1.67 (95% CI:1.10, 2.54) and OR = 1.70 (95% CI:1.13, 2.56), respectively], but not DAC. Other PFAS were not associated with outcomes.

Conclusions: Prediabetic adults with higher plasma concentrations of select PFAS had higher risk of coronary and thoracic aorta calcification. PFAS exposure may be a risk factor for adverse cardiovascular health among high-risk populations.
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http://dx.doi.org/10.1016/j.envint.2021.106446DOI Listing
June 2021

Abnormal liver blood tests among hospitalised patients with SARS-CoV2 (COVID-19).

Frontline Gastroenterol 2021 2;12(2):87-88. Epub 2020 Nov 2.

University of Barcelona, Barcelona, Spain.

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http://dx.doi.org/10.1136/flgastro-2020-101691DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7873541PMC
November 2020

"A hybrid approach for GISTs near the esophagogastric junction, a case report".

Ann Med Surg (Lond) 2021 Feb 20;62:288-292. Epub 2021 Jan 20.

Resident at Clínica Citimed, Quito-Ecuador, Ecuador.

Introduction And Importance: Gastrointestinal stromal tumors are the most frequent mesenchymal tumors of the gastrointestinal tract. Complete resection of GISTs is the only chance of cure for patients. When these tumors are located near the esophagogastric junction, the surgical risk can cause deformity or stenosis in the gastric inlet, leading to higher complications and diminishing their quality of life. In such cases, a more sophisticated and tailored approach should be used.

Case Presentation: We present the case of a 42-year-old female; she presented to our office with a 3-year history of nausea, vomiting and abdominal distension. Two GISTs were located near the EGJ, and with a combined approach we achieved complete resection. On follow-ups, the patient is doing well.

Clinical Discussion Conclusion: When diagnosis is confirmed, surgical resection must be the first choice for GISTs as complete surgical excision is the only permanent cure. The rise of endoscopic surgery has become a valuable tool and a critical element in surgery. Hybrid techniques that combine laparoscopic and endoscopic approaches can improve the patient's outcomes and provide better results.
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http://dx.doi.org/10.1016/j.amsu.2021.01.022DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7841213PMC
February 2021

Per- and polyfluoroalkyl substances and kidney function: Follow-up results from the Diabetes Prevention Program trial.

Environ Int 2021 03 19;148:106375. Epub 2021 Jan 19.

Division of Chronic Disease Research Across the Lifecourse, Department of Population Medicine, Harvard Medical School and Harvard Pilgrim Health Care Institute, Boston, MA, USA. Electronic address:

Per- and polyfluoroalkyl substances (PFAS) are ubiquitously detected in populations worldwide and may hinder kidney function. The objective of the study was to determine longitudinal associations of plasma PFAS concentrations with estimated glomerular filtration rate (eGFR) and evaluate whether a lifestyle intervention modify the associations. We studied 875 participants initially randomized to the lifestyle or placebo arms in the Diabetes Prevention Program (DPP, 1996-2002) trial and Outcomes Study (DPPOS, 2002-2014). We ran generalized linear mixed models accounting a priori covariates to evaluate the associations between baseline PFAS concentrations and repeated measures of eGFR, separately, for six PFAS (PFOS, PFOA, PFHxS, EtFOSAA, MeFOSAA, PFNA); then used quantile-based g-computation to evaluate the effects of the six PFAS chemicals as a mixture. The cohort was 64.9% female; 73.4% 40-64 years-old; 29.4% with hypertension; 50.5% randomized to lifestyle intervention and 49.5% to placebo and had similar plasma PFAS concentrations as the general U.S. population in 1999-2000. Most participants had normal kidney function (eGFR > 90 mL/min/1.73 m) over the approximately 14 years of follow-up. We found that plasma PFAS concentrations during DPP were inversely associated with eGFR during DPPOS follow-up. Each quartile increase in baseline plasma concentration of the 6 PFAS as a mixture was associated with 2.26 mL/min/1.73 m lower eGFR (95% CI: -4.12, -0.39) at DPPOS Year 5, approximately 9 years since DPP randomization and PFAS measurements. The lifestyle intervention did not modify associations, but inverse associations were stronger among participants with hypertension at baseline. Among prediabetic adults, we found inverse associations between baseline plasma PFAS concentrations and measures of eGFR throughout 14 years of follow-up. The lifestyle intervention of diet, exercise and behavioral changes did not modify the associations, but persons with hypertension may have heightened susceptibility.
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http://dx.doi.org/10.1016/j.envint.2020.106375DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7929640PMC
March 2021

Hyperkalemia influences the outcome of patients with cirrhosis with acute decompensation (AD) and acute-on-chronic liver failure (ACLF).

Dig Liver Dis 2021 Jan 11. Epub 2021 Jan 11.

Liver Unit, Hospital Clinic, Spain; Institut d'Investigacions Biomediques August Pi I Sunyer (IDIBAPS), y Centro de Investigaciones en Red Hepaticas y Digestivas (CIBERehd), Barcelona, Catalonia, Spain; Faculty of Medicine and health sciences, University of Barcelona. Electronic address:

Introduction: The presence of hyperkalemia in different clinical scenarios has been described as a risk factor for mortality. Information about this electrolyte disorder in patients with cirrhosis is limited and there are no data in patients with acute-on-chronic liver failure (ACLF).

Aim: The aim of this study was to investigate whether hyperkalemia is a risk factor for mortality in patients with cirrhosis and acute decompensation (AD) with and without ACLF.

Methods: We performed an analysis of the Chronic Liver Failure Consortium CANONIC database in 1,314 consecutive patients admitted to 29 European centers with AD both with and without associated ACLF (294 and 1020 respectively). Hyperkalemia was defined as serum potassium ≥ 5.0 mEq/L. All patients had at least one valid measure of serum potassium from admission and/or through the whole hospitalization.

Results: 1314 patients were admitted with AD and 294 of them had ACLF at admission. Prevalence of hyperkalemia was significantly higher in ACLF versus AD (22.4% and 8.6% respectively, p<0.001). Hyperkalemia was associated with an increased 90, 180 and 360-day mortality risk in ACLF compared to AD (HR 10 vs 2.3 at 90-day p<0.001, 8.9 vs 3.1 at 180-day, p<0.001 and 5.8 vs 3.8 at 360-day, p<0.001). In a multivariate analysis, the presence of hyperkalemia during admission was independently associated with 90-day mortality [HR 2.4 (1.7 - 3.4)]. Variability of potassium between two valid measures ≥ 0.9 mg/dl was always also associated with a higher mortality rate. Addition of hyperkalemia to MELD score (MELD-K model) improved the accuracy to predict 90-day mortality risk.

Conclusions: Hyperkalemia is an independent risk factor of mortality in patients with AD and ACLF. Addition of hyperkalemia to the MELD score improves diagnostic accuracy to predict 90-day mortality in patients with AD and ACLF.
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http://dx.doi.org/10.1016/j.dld.2020.12.009DOI Listing
January 2021

Global burden of disease: acute-on-chronic liver failure, a systematic review and meta-analysis.

Gut 2021 Jan 12. Epub 2021 Jan 12.

Gastroenterology and Hepatology, Depatment of Medicine, Baylor College of Medicine, Houston, Texas, USA

Background And Aims: Acute-on-chronic liver failure (ACLF) is characterised by acute decompensation of cirrhosis associated with organ failures. We systematically evaluated the geographical variations of ACLF across the world in terms of prevalence, mortality, aetiology of chronic liver disease (CLD), triggers and organ failures.

Methods: We searched EMBASE and PubMed from 3/1/2013 to 7/3/2020 using the ACLF-EASL-CLIF (European Association for the Study of the Liver-Chronic Liver Failure) criteria. Two investigators independently conducted the abstract selection/abstraction of the aetiology of CLD, triggers, organ failures and prevalence/mortality by presence/grade of ACLF. We grouped countries into Europe, East/South Asia and North/South America. We calculated the pooled proportions, evaluated the methodological quality using the Newcastle-Ottawa Scale and statistical heterogeneity, and performed sensitivity analyses.

Results: We identified 2369 studies; 30 cohort studies met our inclusion criteria (43 206 patients with ACLF and 140 835 without ACLF). The global prevalence of ACLF among patients admitted with decompensated cirrhosis was 35% (95% CI 33% to 38%), highest in South Asia at 65%. The global 90-day mortality was 58% (95% CI 51% to 64%), highest in South America at 73%. Alcohol was the most frequently reported aetiology of underlying CLD (45%, 95% CI 41 to 50). Infection was the most frequent trigger (35%) and kidney dysfunction the most common organ failure (49%). Sensitivity analyses showed regional estimates grossly unchanged for high-quality studies. Type of design, country health index, underlying CLD and triggers explained the variation in estimates.

Conclusions: The global prevalence and mortality of ACLF are high. Region-specific variations could be explained by the type of triggers/aetiology of CLD or grade. Health systems will need to tailor early recognition and treatment of ACLF based on region-specific data.
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http://dx.doi.org/10.1136/gutjnl-2020-322161DOI Listing
January 2021

Added sugar intake during pregnancy: Fetal behavior, birth outcomes, and placental DNA methylation.

Dev Psychobiol 2021 Jan 7. Epub 2021 Jan 7.

Department of Psychiatry, Division of Behavioral Medicine, Columbia University Medical Center, New York, NY, USA.

Pregnancy is a critical time for the effects of environmental factors on children's development. The effect of added sugar intake on fetal development and pregnancy outcomes remains understudied despite increasing dietary intake in the United States. This study investigated the effect of added sugar on fetal programming by examining the association between maternal added sugar consumption, fetal movement, birth outcomes, and placental DNA methylation. Further, primary human fibroblasts were cultured under normal or high glucose conditions to assess the effect of high glucose exposure on cells' DNA methylation. We found that higher added sugar intake across pregnancy was associated with reduced 3rd-trimester fetal movement (p < .05) and shorter gestation (p < .01). Our sample size was not powered to detect the alteration of individual placental CpG with genome-wide significance. However, a secondary analysis suggested that added sugar consumption was associated with differential methylation of functionally related gene families across pregnancy. Consistent with this, high glucose exposure in primary cultured human fibroblasts altered the methylation of 17% of all CpGs, providing converging evidence for an effect of sugar on DNA methylation. Our results suggest that diets high in added sugar during pregnancy may have implications for offspring health via prenatal programming effects measurable before birth.
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http://dx.doi.org/10.1002/dev.22088DOI Listing
January 2021

Maternal anxiety during pregnancy and newborn epigenome-wide DNA methylation.

Mol Psychiatry 2021 Jan 7. Epub 2021 Jan 7.

Erasmus MC, University Medical Center Rotterdam, Generation R Study Group, Rotterdam, The Netherlands.

Maternal anxiety during pregnancy is associated with adverse foetal, neonatal, and child outcomes, but biological mechanisms remain unclear. Altered foetal DNA methylation (DNAm) has been proposed as a potential underlying mechanism. In the current study, we performed a meta-analysis to examine the associations between maternal anxiety, measured prospectively during pregnancy, and genome-wide DNAm from umbilical cord blood. Sixteen non-overlapping cohorts from 12 independent longitudinal studies of the Pregnancy And Childhood Epigenetics Consortium participated, resulting in a combined dataset of 7243 mother-child dyads. We examined prenatal anxiety in relation to genome-wide DNAm and differentially methylated regions. We observed no association between the general symptoms of anxiety during pregnancy or pregnancy-related anxiety, and DNAm at any of the CpG sites, after multiple-testing correction. Furthermore, we identify no differentially methylated regions associated with maternal anxiety. At the cohort-level, of the 21 associations observed in individual cohorts, none replicated consistently in the other cohorts. In conclusion, contrary to some previous studies proposing cord blood DNAm as a promising potential mechanism explaining the link between maternal anxiety during pregnancy and adverse outcomes in offspring, we found no consistent evidence for any robust associations between maternal anxiety and DNAm in cord blood. Larger studies and analysis of DNAm in other tissues may be needed to establish subtle or subgroup-specific associations between maternal anxiety and the foetal epigenome.
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http://dx.doi.org/10.1038/s41380-020-00976-0DOI Listing
January 2021

Epigenome-wide association study of maternal hemoglobin A1c in pregnancy and cord blood DNA methylation.

Epigenomics 2021 Feb 7;13(3):203-218. Epub 2021 Jan 7.

Department of Population Medicine, Harvard Pilgrim Health Care Institute, Harvard Medical School, Boston, MA 02215, USA.

Gestational hyperglycemia is associated with adverse perinatal outcomes and long-term offspring metabolic programming, likely through dysregulation of DNA methylation (DNAm). We tested associations between maternal HbA1c and cord blood DNAm among 412 mother-child pairs in the genetics of glucose regulation in gestation and growth (Gen3G) and implemented Mendelian randomization to infer causality. We sought replication in an independent sample from Healthy Start. Higher second trimester HbA1c levels were associated with lower DNAm at cg21645848 (p = 3.9 × 10) near . Mendelian randomization and replication analyses showed same direction of effect between HbA1c and DNAm at cg21645848, but did not reach statistical significance. We found that higher maternal glycemia reflected by HbA1c is associated with cord blood DNAm at , a gene related with inflammatory pathways.
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http://dx.doi.org/10.2217/epi-2020-0279DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7907967PMC
February 2021

A bleeding GIST in pandemic times, a cooperative approach to a delayed complication, a case report.

Int J Surg Case Rep 2020 2;77:880-884. Epub 2020 Dec 2.

PGY3 General Surgery PUCE, Quito, Ecuador. Electronic address:

Introduction: Upper gastrointestinal bleeding is one of the major manifestations of the stomach's gastrointestinal stromal tumors; when gastric GISTs bleed, they are associated with a poor prognosis and must be treated promptly to avoid dangerous complications. A worrisome side effect of the Covid-19 pandemic is the delay in surgical treatment for seriously ill patients, a rise in surgical complications due to delayed care, lack of access to the healthcare system, and patients' hesitancy to seek care due to fear of the virus. In Ecuador, where limitations were present even in the absence of a pandemic, we are yet to fully know the full extent of the damage this pandemic has caused to ourselves and our patients.

Presentation Of Case: We present the case of a 51-year-old female; she presented with upper gastrointestinal bleeding, and a gastric GIST was diagnosed. Due to the size and the symptoms, surgery was planned. Nonetheless, as Ecuador was hit hard by the Covid-19 pandemic to cope with the respiratory patients, surgeries were delayed or canceled. Our patient surgery was delayed for five months until she presented with severe gastrointestinal bleeding that required urgent action and care. Thankfully, she completely recovered.

Discussion And Conclusions: This case is an example of the many complications we expect due to the pandemic; delay in treatment leads to troublesome complications. In these emergencies, time is of the essence, and surgical services must rise to the challenge; in a particular way, this case also proves that if there are the necessary tools to enhance the patient's recovery, we should hesitate to use them. Complete resection of the gastric GIST in a prompt matter must be done to avoid these potentially deadly complications.
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http://dx.doi.org/10.1016/j.ijscr.2020.11.138DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7732962PMC
December 2020

Re: Fouad Y, et al. The NAFLD-MAFLD debate: Eminence versus evidence. Liver Int. 2020 Nov 21. doi: 10.1111/liv.14739.

Liver Int 2021 May 2;41(5):1162-1163. Epub 2021 Jan 2.

GI/Liver Unit, Institut Clínic de Malalties Digestives i Metabòliques, Hospital Clínic, and University of Barcelona, Barcelona, Spain.

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http://dx.doi.org/10.1111/liv.14750DOI Listing
May 2021

A Longitudinal Epigenetic Aging and Leukocyte Analysis of Simulated Space Travel: The Mars-500 Mission.

Cell Rep 2020 12 25;33(10):108406. Epub 2020 Nov 25.

Division of Environmental Health Sciences, School of Public Health and Center for Computational Biology, University of California, Berkeley, Berkeley, CA 94720, USA.

Astronauts undertaking long-duration space missions may be vulnerable to unique stressors that can impact human aging. Nevertheless, few studies have examined the relationship of mission duration with DNA-methylation-based biomarkers of aging in astronauts. Using data from the six participants of the Mars-500 mission, a high-fidelity 520-day ground simulation experiment, we tested relationships of mission duration with five longitudinally measured blood DNA-methylation-based metrics: DNAmGrimAge, DNAmPhenoAge, DNA-methylation-based estimator of telomere length (DNAmTL), mitotic divisions (epigenetic mitotic clock [epiTOC2]), and pace of aging (PoA). We provide evidence that, relative to baseline, mission duration was associated with significant decreases in epigenetic aging. However, only decreases in DNAmPhenoAge remained significant 7 days post-mission. We also observed significant changes in estimated proportions of plasmablasts, CD4T, CD8 naive, and natural killer (NK) cells. Only decreases in NK cells remained significant post-mission. If confirmed more broadly, these findings contribute insights to improve the understanding of the biological aging implications for individuals experiencing long-duration space travel.
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http://dx.doi.org/10.1016/j.celrep.2020.108406DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7786521PMC
December 2020

Is it possible for a simultaneous biomodification during acid etching on naturally caries-affected dentin bonding?

Clin Oral Investig 2020 Nov 16. Epub 2020 Nov 16.

Department of Restorative Dentistry, School of Dentistry, State University of Ponta Grossa, Avenida Carlos Cavalcanti 4748, Uvaranas, Ponta Grossa, Paraná, 84030-900, Brazil.

Objectives: This study investigated the ability of modified phosphoric acids containing chlorhexidine (CHX) or grape seed extract (GSE) for promoting simultaneous biomodification during acid etching on bonding properties in caries-affected dentin (CAD).

Materials And Methods: Thirty-two human molars (8 with sound dentin [SD] and 24 naturally CAD) were selected for the study. The SD and CAD were initially exposed, then randomized and etched according to the following groups: (1) SD (SD-CT) and CAD (CAD-CT) both with 37% phosphoric acid, (2) CAD with 2% CHX containing 37% phosphoric acid (CAD-CHX), and (3) CAD with 2% GSE containing 10% phosphoric acid (CAD-GSE). The bonding procedure and composite build-ups were performed after acid etching. Subsequently, they were sectioned in resin-dentin specimens. The specimens were submitted for chemical profiling by micro-Raman, microtensile bond strength (μTBS), failure mode with chemical characterization by FEG/SEM-EDX, and in situ zymography by CLSM. The data from μTBS and CLSM were statistically analyzed (1-way ANOVA and Tukey's test; α = 0.05).

Results: The highest μTBS results were shown for SD-CT in comparison with all CAD groups (p < 0.001), and the lowest for CAD-CT and CAD-CHX (p < 0.001). The etching with CHX did not increase the μTBS for CAD when compared with CT (p = 0.52). However, the etching with GSE improved significantly the μTBS for CAD when compared with CT and CHX (p < 0.001). The chemical profile detected chemical and structural changes in collagen peaks for CAD-CT, which were not detected when the CAD was etched by modified acids. Also, the poorest hybridization ability was detected in CAD for CT, which was significantly improved with modified acids, especially the GSE, as evaluated by chemical profile and failure mode. A significant reduction of MMP activity on CAD was promoted by modified acids in comparison with CT (both p < 0.001).

Conclusions: The GSE-containing acid was able to promote biomodification during the acid etching, increasing the bonding properties and reducing the activity of the MMPs within the hybrid layer.

Clinical Relevance: The use of GSE-containing phosphoric acid can be a promising alternative to improve the bonding performance on caries-affected dentin, since it is capable of biomodifying the dentin during the acid etching, without adding any extra step in bonding procedures.
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http://dx.doi.org/10.1007/s00784-020-03677-8DOI Listing
November 2020

Exposure to violence, chronic stress, nasal DNA methylation, and atopic asthma in children.

medRxiv 2020 Nov 4. Epub 2020 Nov 4.

Background: Exposure to violence (ETV) or stress may cause asthma through unclear mechanisms.

Methods: Epigenome-wide association study (EWAS) of DNA methylation in nasal epithelium and four ETV or chronic stress measures in 487 Puerto Ricans aged 9-20 years who participated in the Epigenetic Variation and Childhood Asthma in Puerto Ricans study [EVA-PR]). We assessed measures of ETV or chronic stress in children (ETV scale, gun violence, and perceived stress) and their mothers (perceived stress). Each EWAS was conducted using linear regression, with CpGs as dependent variables and the stress/violence measure as a predictor, adjusting for age, sex, the top five principal components, and SVA latent factors. We then selected the top 100 CpGs (by P-value) associated with each stress/violence measure in EVA-PR and conducted a meta-analysis of the selected CpGs and atopic asthma using data from EVA-PR and two additional cohorts (Project Viva and PIAMA).

Results: In the EWAS of stress/violence in EVA-PR, gun violence was associated with methylation of cg18961589 in (β=0.03, =1.28×10 ), and maternal stress was associated with methylation of cg03402351 in (β=0.04, =1.69×10 ) and cg19064846 in (β=0.03, =3.36×10 ). In a meta-analysis of three cohorts, which included the top CpGs associated with stress/violence in EVA-PR, CpGs in and were associated with atopic asthma at FDR- < 0.05.

Conclusions: ETV and chronic stress may increase the risk of atopic asthma through DNA methylation in airway epithelium, though this needs confirmation in future longitudinal studies.
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http://dx.doi.org/10.1101/2020.11.03.20225250DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7654924PMC
November 2020

Placental Epigenome-Wide Association Study Identified Loci Associated with Childhood Adiposity at 3 Years of Age.

Int J Mol Sci 2020 Sep 29;21(19). Epub 2020 Sep 29.

Department of Biochemistry and Functional Genomics, Université de Sherbrooke, Sherbrooke, QC J1H 5N4, Canada.

The aim of this study was to identify placental DNA methylation (DNAm) variations associated with adiposity at 3 years of age. We quantified placental DNAm using the Infinium MethylationEPIC BeadChips. We assessed associations between DNAm at single-CpGs and skinfold thickness using robust linear regression models adjusted for gestational age, child's sex, age at follow-up and cellular heterogeneity. We sought replication of DNAm association with child adiposity in an independent cohort. We quantified placental mRNA levels for annotated gene using qRT-PCR and tested for correlation with DNAm. Lower DNAm at cg22593959 and cg22436429 was associated with higher adiposity ( = -1.18, = 0.002 and = -0.82, = 0.04). The cg22593959 is located in an intergenic region (chr7q31.3), whereas cg22436429 is within the gene (1p34.3). DNAm at cg22593959 and cg22436429 was correlated with mRNA levels at (r = -0.279, = 0.005) and (r = 0.216, = 0.03). In an independent cohort, the association between placental DNAm at cg22593959 and childhood adiposity was of similar strength and direction ( = -3.8 ± 4.1, = 0.36), yet non-significant. Four genomic regions were also associated with skinfold thickness within , , and genes. We identified placental epigenetic variations associated with adiposity at 3 years of age suggesting that childhood fat accretion patterns might be established during fetal life.
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http://dx.doi.org/10.3390/ijms21197201DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7582906PMC
September 2020

DNA Methylation Architecture of the ACE2 gene in Nasal Cells.

medRxiv 2020 Sep 16. Epub 2020 Sep 16.

Division of Chronic Disease Research Across the Lifecourse, Department of Population Medicine, Harvard Medical School and Harvard Pilgrim Health Care Institute, Boston, MA, USA.

Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) has led to the global coronavirus disease 2019 (COVID-19) pandemic. SARS-CoV-2 enters cells via angiotensin-Converting Enzyme 2 (ACE2) receptors, highly expressed in nasal epithelium with parallel high infectivity.1,2 The nasal epigenome is in direct contact with the environment and could explain COVID-19 disparities by reflecting social and environmental influences on ACE2 regulation. We collected nasal swabs from anterior nares of 547 children, measured DNA methylation (DNAm), and tested differences at 15 ACE2 CpGs by sex, age, race/ethnicity and epigenetic age. ACE2 CpGs were differentially methylated by sex with 12 sites having lower DNAm (mean=12.71%) and 3 sites greater DNAm (mean=1.45%) among females relative to males. We observed differential DNAm at 5 CpGs for Hispanic females (mean absolute difference=3.22%) and lower DNAm at 8 CpGs for Black males (mean absolute difference=1.33%), relative to white participants. Longer DNAm telomere length was associated with greater ACE2 DNAm at 11 and 13 CpGs among males (mean absolute difference=7.86%) and females (mean absolute difference=8.21%), respectively. Nasal ACE2 DNAm differences could contribute to our understanding COVID-19 severity and disparities reflecting upstream environmental and social influences.
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http://dx.doi.org/10.1101/2020.08.25.20182105DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7523147PMC
September 2020

Effect of surface treatments on the adhesive properties of metallic brackets on fluorotic enamel.

Dental Press J Orthod 2020 Jul-Aug;25(4):59-67

Escuela Odontologia, Facultad de Ciencias de la Salud "Eugenio Espejo", Universidad UTE (Quito, Ecuador).

Objective: To compare the effectiveness of the pretreatment with sandblasting and deproteinization with NaOCl on bond strength (SBS), in situ conversion degree (CD) of brackets in fluorotic enamel, and enamel etching pattern.

Methods: A total of 90 non-carious maxillary premolars were used. The teeth were then assigned to six experimental groups according to: enamel surface (sound and fluorotic enamel); surface treatment (Regular etch with 37% phosphoric acid [RE]; 5.2% sodium hypochlorite + phosphoric acid [NaOCl + RE]; sandblasting + phosphoric acid [sandblasting + RE]). After storage in distilled water (37°C/24h), the specimens were tested at 1 mm/min until failure (SBS). Enamel-resin cement interfaces were evaluated for CD using micro-Raman spectroscopy. The enamel-etching pattern was evaluated under a scanning electron microscope. Data from SBS and in situ CD values were analyzed using ANOVA two-away and Tukey test (α=0.05). The enamel etching pattern was evaluated only qualitatively.

Results: For sound enamel, RE showed the highest SBS values, when compared to NaOCl + RE and Sandblasting + RE groups (p< 0.01). Regarding CD, only NaOCl + RE significantly compromised the mean DC, in comparison with other groups (p= 0.002). For fluorotic enamel, the Sandblasting + RE group significantly increased the mean SBS values, in comparison with RE group (p= 0.01) and no significant change was observed for CD (p> 0.52).

Conclusions: The application of NaOCl or sandblasting associated to phosphoric acid improved the SBS of the brackets in fluorotic enamel without compromising the CD of the resin cement, with improving of enamel interprismatic conditioning.
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http://dx.doi.org/10.1590/2177-6709.25.4.059-067.oarDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7510489PMC
September 2020

Colon capsule endoscopy versus CT colonography in FIT-positive colorectal cancer screening subjects: a prospective randomised trial-the VICOCA study.

BMC Med 2020 09 18;18(1):255. Epub 2020 Sep 18.

Gastroenterology Department, Hospital Clinic of Barcelona, Barcelona, Spain.

Background: Colon capsule endoscopy (CCE) and CT colonography (CTC) are minimally invasive techniques for colorectal cancer (CRC) screening. Our objective is to compare CCE and CTC for the identification of patients with colorectal neoplasia among participants in a CRC screening programme with positive faecal immunochemical test (FIT). Primary outcome was to compare the performance of CCE and CTC in detecting patients with neoplastic lesions.

Methods: The VICOCA study is a prospective, single-centre, randomised trial conducted from March 2014 to May 2016; 662 individuals were invited and 349 were randomised to CCE or CTC before colonoscopy. Endoscopists were blinded to the results of CCE and CTC.

Results: Three hundred forty-nine individuals were included: 173 in the CCE group and 176 in the CTC group. Two hundred ninety individuals agreed to participate: 147 in the CCE group and 143 in the CTC group. In the intention-to-screen analysis, sensitivity, specificity and positive and negative predictive values for the identification of individuals with colorectal neoplasia were 98.1%, 76.6%, 93.7% and 92.0% in the CCE group and 64.9%, 95.7%, 96.8% and 57.7% in the CTC group. In terms of detecting significant neoplastic lesions, the sensitivity of CCE and CTC was 96.1% and 79.3%, respectively. Detection rate for advanced colorectal neoplasm was higher in the CCE group than in the CTC group (100% and 93.1%, respectively; RR = 1.07; p = 0.08). Both CCE and CTC identified all patients with cancer. CCE detected more patients with any lesion than CTC (98.6% and 81.0%, respectively; RR = 1.22; p = 0.002).

Conclusion: Although both techniques seem to be similar in detecting patients with advanced colorectal neoplasms, CCE is more sensitive for the detection of any neoplastic lesion.

Trial Registration: ClinicalTrials.gov Identifier: NCT02081742 . Registered: September 16, 2013.
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http://dx.doi.org/10.1186/s12916-020-01717-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7500543PMC
September 2020