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1.
Gastric Cancer ; 27(4): 747-759, 2024 Jul.
Article in English | MEDLINE | ID: mdl-38796558

ABSTRACT

BACKGROUND: CDH1 and CTNNA1 remain as the main genes for hereditary gastric cancer. However, they only explain a small fraction of gastric cancer cases with suspected inherited basis. In this study, we aimed to identify new hereditary genes for early-onset gastric cancer patients (EOGC; < 50 years old). METHODS: After germline exome sequencing in 20 EOGC patients and replication of relevant findings by gene-panel sequencing in an independent cohort of 152 patients, CTNND1 stood out as an interesting candidate gene, since its protein product (p120ctn) directly interacts with E-cadherin. We proceeded with functional characterization by generating two knockout CTNND1 cellular models by gene editing and introducing the detected genetic variants using a lentiviral delivery system. We assessed ß-catenin and E-cadherin levels, cell detachment, as well as E-cadherin localization and cell-to-cell interaction by spheroid modeling. RESULTS: Three CTNND1 germline variants [c.28_29delinsCT, p.(Ala10Leu); c.1105C > T, p.(Pro369Ser); c.1537A > G, p.(Asn513Asp)] were identified in our EOGC cohorts. Cells encoding CTNND1 variants displayed altered E-cadherin levels and intercellular interactions. In addition, the p.(Pro369Ser) variant, located in a key region in the E-cadherin/p120ctn binding domain, showed E-cadherin mislocalization. CONCLUSIONS: Defects in CTNND1 could be involved in germline predisposition to gastric cancer by altering E-cadherin and, consequently, cell-to-cell interactions. In the present study, CTNND1 germline variants explained 2% (3/172) of the cases, although further studies in larger external cohorts are needed.


Subject(s)
Cadherins , Catenins , Delta Catenin , Genetic Predisposition to Disease , Germ-Line Mutation , Stomach Neoplasms , Stomach Neoplasms/genetics , Stomach Neoplasms/pathology , Humans , Male , Catenins/genetics , Catenins/metabolism , Female , Middle Aged , Adult , Cadherins/genetics , Cell Communication , Age of Onset , Antigens, CD
2.
J Phys Chem A ; 128(20): 4083-4091, 2024 May 23.
Article in English | MEDLINE | ID: mdl-38723198

ABSTRACT

The exploration of phosphorus-bearing species stands as a prolific field in current astrochemical research, particularly within the context of prebiotic chemistry. Herein, we have employed high-level quantum chemistry methodologies to predict the structure and spectroscopic properties of isomers composed of a methyl group and three P, C, and O atoms. We have computed relative and dissociation energies, as well as rotational, rovibrational, and torsional parameters using the B2PLYPD3 functional and the explicitly correlated coupled cluster CCSD(T)-F12b method. Based upon our study, all the isomers exhibit a bent heavy atom skeleton with CH3PCO being the most stable structure, regardless of the level theory employed. Following in energy, we found four high-energy isomers, namely, CH3OCP, CH3CPO, CH3COP, and CH3OPC. The computed adiabatic dissociation energies support the stability of all [CH3, P, C, O] isomers against fragmentation into CH3 and [P, C, O]. Torsional barrier heights associated with the methyl internal rotation for each structure have been computed to evaluate the occurrence of possible A-E splittings in the rotational spectra. For the most stable isomer, CH3PCO, we found a V3 barrier of 82 cm-1, which is slightly larger than that obtained experimentally for the N-counterpart, CH3NCO, yet still very low. Therefore, the analysis of its rotational spectrum can be anticipated as a challenging task owing to the effect of the CH3 internal rotation. The complete set of spectroscopic constants and transition frequencies reported here for the most stable isomer, CH3PCO, is intended to facilitate eventual laboratory searches.

3.
Cancer Med ; 13(5): e6923, 2024 Mar.
Article in English | MEDLINE | ID: mdl-38491824

ABSTRACT

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


Subject(s)
COVID-19 , Colorectal Neoplasms , Rectal Neoplasms , Humans , SARS-CoV-2 , COVID-19/epidemiology , COVID-19/prevention & control , Pandemics , Prospective Studies , Communicable Disease Control , Prognosis , Colorectal Neoplasms/diagnosis , Colorectal Neoplasms/epidemiology , Retrospective Studies , COVID-19 Testing
4.
Gastroenterol. hepatol. (Ed. impr.) ; 47(3): 246-252, mar. 2024. ilus, tab, graf
Article in English | IBECS | ID: ibc-231205

ABSTRACT

Background and objectives There are few scales with prospective validation for the assessment of the upper gastrointestinal mucosal cleanliness during an esophagogastroduodenoscopy (EGD). The aim of this study was to develop a valid and reproducible cleanliness scale for use during an EGD. Methods We developed a cleanliness scale (Barcelona scale) with a score (0–2 points) of five segments of the upper gastrointestinal tract with thorough cleaning techniques (esophagus, fundus, body, antrum, and duodenum). First, 125 photos (25 of each area) were assessed, and a score was assigned to each image by consensus among 7 experts endoscopists. Subsequently, 100 of the 125 images were selected and the inter- and intra-observer variability of 15 previously trained endoscopists was evaluated using the same images at two different times. Results In total, 1500 assessments were performed. In 1336/1500 observations (89%) there was agreement with the consensus score, with a mean kappa value of 0.83 (0.45–0.96). In the second evaluation, in 1330/1500 observations (89%) there was agreement with the consensus score, with a mean kappa value of 0.82 (0.45–0.93). The intra-observer variability was 0.89 (0.76–0.99). Conclusions The Barcelona cleanliness scale is a valid measure and reproducible with minimal training. Its application in clinical practice is a significant step to standardize the quality of the EGD. (AU)


Introducción Existen pocas escalas validadas prospectivamente para evaluar la limpieza de la mucosa esofagogastroduodenal durante la endoscopia digestiva alta (EDA). El objetivo de este estudio fue desarrollar una escala válida y reproducible para su uso en la realización de una EDA. Métodos Desarrollamos una escala de limpieza (escala Barcelona) en la que se aplicó una puntuación de 0 a 2 a cinco áreas del tracto digestivo superior (esófago, fundus, cuerpo, antro y duodeno) después de haber realizado todas las maniobras de lavado necesarias. Inicialmente, se evaluaron 125 fotos (25 de cada área) y se asignó una puntuación (de 0 a 2) a cada una por consenso entre siete endoscopistas. Posteriormente, se seleccionaron 100 de las 125 fotografías y se evaluó la variabilidad inter e intraobservador de 15 endoscopistas previamente formados utilizando las mismas imágenes en dos momentos diferentes. Resultados Se efectuaron un total de 1.500 observaciones. En 1.336/1.500 de ellas (89%) hubo coincidencia con la puntuación del consenso, siendo el valor medio de kappa de 0,83 (0,45-0,96). En la segunda evaluación, en 1.330/1.500 observaciones (89%) hubo coincidencia con la puntuación del consenso, siendo el valor medio de kappa de 0,82 (mínimo 0,45 y máximo 0,93). La variabilidad intraobservador fue de 0,89 (0,76-0,99). Conclusiones La escala de limpieza Barcelona es una medida válida y reproducible con un mínimo entrenamiento. Su uso en la práctica clínica podría ser un paso significativo para estandarizar la calidad de la EDA. (AU)


Subject(s)
Endoscopy, Digestive System/methods , Endoscopy, Digestive System/statistics & numerical data , Prospective Studies
5.
Gastroenterol. hepatol. (Ed. impr.) ; 47(1): 1-13, ene. 2024. tab
Article in English | IBECS | ID: ibc-229081

ABSTRACT

Introduction The Colonoscopy Satisfaction and Safety Questionnaire based on Patient experience (CSSQP) was recently developed and validated within a Bowel Cancer Screening Program. We aimed to identify factor related to patient experience through the CSSQP, including all indications for colonoscopy. Indicators of satisfaction and perceived safety with colonoscopy were also assessed to compare the different centers. Methods Multicenter study in nine Spanish hospitals. Consecutive patients who had undergone a colonoscopy completed the CSSQP adding a novel item on bowel preparation. Factors related to patient experiences and data from non-respondents were analyzed. Results Of 2200 patients, 1753 filled out the questionnaire (response rate 79.7%, sample error 2%). Patients whose colonoscopy indication was a primary colorectal cancer screening (OR: 1.68, 95% CI: 1.15–2.44, p=0.007) or due to a +FIT (OR: 1.73, 95% CI: 1.18–2.53) reported higher satisfaction than patients with gastrointestinal symptoms. In addition, college-educated patients (OR: 2.11, 95% CI: 1.25–3.56) were more likely to report better overall satisfaction than patients with lower education level. Significant differences were observed in the majority of the CSSQP items between centers. Safety incidents were reported by 35 (2%) patients, and 176 (10%) patients reported that they received insufficient information. Conclusion The CSSQP identifies several significant factors on satisfaction and perceived safety in patients referred for colonoscopy for any reason. The CSSQP also allows comparison of patient-identified colonoscopy quality indicators between centers (AU)


Introducción El Cuestionario de Satisfacción y Seguridad de la Colonoscopia basado en la experiencia del Paciente (CSSQP) ha sido desarrollado y validado recientemente en pacientes del Programa de cribado de cáncer colorrectal (CCR). El objetivo del estudio fue identificar los factores relacionados con la experiencia de los pacientes a través del CSSQP, incluyendo todas las indicaciones de la colonoscopia. Además, se evaluaron los factores relacionados con la satisfacción y la seguridad del paciente con el fin de comparar diferentes departamentos. Métodos Estudio multicéntrico de nueve hospitales españoles en el que se incluyeron pacientes consecutivos que completaron el CSSQP incorporando un nuevo ítem sobre la preparación intestinal. Se analizaron los factores relacionados con la experiencia de los pacientes y los datos de los no respondedores. Resultados De 2.200 pacientes, 1.753 completaron el cuestionario (tasa de respuesta del 79,7%, error muestral del 2%). Los pacientes en los que la indicación era por cribado de CCR (OR: 1,68; IC 95%: 1,15-2,44; p=0,007) o por FIT positivo (OR: 1,73; IC 95%: 1,18-2,53) informaron mayor satisfacción que en aquellos que se solicitó la colonoscopia por síntomas gastrointestinales. Además, los pacientes con estudios universitarios (OR: 2,11; IC 95%: 1,25-3,56) informaron mayor satisfacción que aquellos con menor nivel de estudios. Se observaron diferencias significativas en la mayoría de los ítems del CSSQP entre los centros participantes. Treinta y cinco (2%) pacientes reportaron incidentes de seguridad y 176 (10%) reconocieron haber recibido información insuficiente. Conclusiones El CSSQP identifica los factores determinantes que influyen en la satisfacción y la seguridad de los pacientes a los que se les realiza colonoscopia por cualquier indicación. Además, permite comparar los indicadores de calidad de la colonoscopia desde la perspectiva del paciente entre los distintos centros (AU)


Subject(s)
Humans , Male , Female , Middle Aged , Aged , Colonoscopy , Patient Satisfaction , Patient Safety , Surveys and Questionnaires , Prospective Studies
6.
Gastroenterol Hepatol ; 47(3): 246-252, 2024 Mar.
Article in English, Spanish | MEDLINE | ID: mdl-37236304

ABSTRACT

BACKGROUND AND OBJECTIVES: There are few scales with prospective validation for the assessment of the upper gastrointestinal mucosal cleanliness during an esophagogastroduodenoscopy (EGD). The aim of this study was to develop a valid and reproducible cleanliness scale for use during an EGD. METHODS: We developed a cleanliness scale (Barcelona scale) with a score (0-2 points) of five segments of the upper gastrointestinal tract with thorough cleaning techniques (esophagus, fundus, body, antrum, and duodenum). First, 125 photos (25 of each area) were assessed, and a score was assigned to each image by consensus among 7 experts endoscopists. Subsequently, 100 of the 125 images were selected and the inter- and intra-observer variability of 15 previously trained endoscopists was evaluated using the same images at two different times. RESULTS: In total, 1500 assessments were performed. In 1336/1500 observations (89%) there was agreement with the consensus score, with a mean kappa value of 0.83 (0.45-0.96). In the second evaluation, in 1330/1500 observations (89%) there was agreement with the consensus score, with a mean kappa value of 0.82 (0.45-0.93). The intra-observer variability was 0.89 (0.76-0.99). CONCLUSIONS: The Barcelona cleanliness scale is a valid measure and reproducible with minimal training. Its application in clinical practice is a significant step to standardize the quality of the EGD.


Subject(s)
Duodenum , Mucous Membrane , Humans , Consensus , Endoscopy, Digestive System
7.
Gastroenterol Hepatol ; 47(1): 1-13, 2024 Jan.
Article in English, Spanish | MEDLINE | ID: mdl-36841528

ABSTRACT

INTRODUCTION: The Colonoscopy Satisfaction and Safety Questionnaire based on Patient experience (CSSQP) was recently developed and validated within a Bowel Cancer Screening Program. We aimed to identify factor related to patient experience through the CSSQP, including all indications for colonoscopy. Indicators of satisfaction and perceived safety with colonoscopy were also assessed to compare the different centers. METHODS: Multicenter study in nine Spanish hospitals. Consecutive patients who had undergone a colonoscopy completed the CSSQP adding a novel item on bowel preparation. Factors related to patient experiences and data from non-respondents were analyzed. RESULTS: Of 2200 patients, 1753 filled out the questionnaire (response rate 79.7%, sample error 2%). Patients whose colonoscopy indication was a primary colorectal cancer screening (OR: 1.68, 95% CI: 1.15-2.44, p=0.007) or due to a +FIT (OR: 1.73, 95% CI: 1.18-2.53) reported higher satisfaction than patients with gastrointestinal symptoms. In addition, college-educated patients (OR: 2.11, 95% CI: 1.25-3.56) were more likely to report better overall satisfaction than patients with lower education level. Significant differences were observed in the majority of the CSSQP items between centers. Safety incidents were reported by 35 (2%) patients, and 176 (10%) patients reported that they received insufficient information. CONCLUSION: The CSSQP identifies several significant factors on satisfaction and perceived safety in patients referred for colonoscopy for any reason. The CSSQP also allows comparison of patient-identified colonoscopy quality indicators between centers.


Subject(s)
Colorectal Neoplasms , Patient Satisfaction , Humans , Colonoscopy/adverse effects , Colorectal Neoplasms/diagnosis , Surveys and Questionnaires , Patient Outcome Assessment
8.
Pap. psicol ; 44(3): 156-163, Sept. 2023.
Article in Spanish | IBECS | ID: ibc-225266

ABSTRACT

La evolución de los programas de CRM ha supuesto para la aviación un enorme progreso en cuanto al estudio de los factores humanos y su relación con la reducción de los accidentes aéreos. Si bien es cierto que los programas de CRM han sufrido una exitosa evolución desde su aparición en 1979, no lo es menos, que los avances en la ciencia psicológica de las últimas décadas hacen necesario revisar y profundizar en aspectos ya abordados en etapas anteriores por dichos programas. Uno de estos aspectos es la importancia que presentan los Tripulantes de Cabina de Pasajeros (TCP) como integrantes del equipo de vuelo. Retrotrayéndose a los programas de CRM de tercera generación, el presente artículo analiza las actuaciones que han tenido los TCP en diferentes accidentes aéreos, poniendo de manifiesto la importancia que tiene su ejecución y la coordinación de la misma con la del resto de la tripulación de cara al éxito en la resolución de la emergencia aérea.(AU)


The evolution of CRM programs has meant enormous progress for aviation in terms of the study of human factors and their relationship with the reduction of air accidents. Although it is true that CRM programs have undergone a successful evolution since their appearance in 1979, it is no less true that the advances in psychological science in recent decades make it necessary to review and expand on aspects already addressed in previous stages by these programs. One of these aspects is the importance of the cabin crew members (CCM) as members of the flight team. Going back to the third generation programs, this paper analyzes the actions that the CCM have taken in different air accidents, highlighting the importance of their performance and their coordination with the rest of the crew in order to achieve success in resolving the air emergency.(AU)


Subject(s)
Humans , Program Evaluation , Aviation/education , Accidents, Aviation/psychology , Air Travel/psychology
9.
Ann Intern Med ; 176(9): 1145-1152, 2023 09.
Article in English | MEDLINE | ID: mdl-37639723

ABSTRACT

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


Subject(s)
Artificial Intelligence , Colorectal Neoplasms , Humans , Colorectal Neoplasms/diagnosis , Colonoscopy , Odds Ratio , Radiopharmaceuticals
14.
Rev. esp. enferm. dig ; 114(12): 719-724, diciembre 2022. tab
Article in English | IBECS | ID: ibc-213524

ABSTRACT

Background: colonoscopy is the gold standard method forthe early diagnosis and prevention of colorectal cancer(CRC). Screening programs include immune determinationof blood in feces. Regardless of the method used, proximalcolon lesions appear to be detected less frequently.Objective: to analyze the characteristics of proximal anddistal lesions and possible predisposing factors.Methods: a cross-sectional study was performed of 692patients from the CRC screening program with fecal immunological test (FIT) ≥ 100 ngHb/ml (October 2017-October2018). The right colon was examined twice as patients wereparticipating in a randomized clinical trial to re-evaluatethe right colon by forward-viewing endoscope or proximalretroflexion. The adenoma detection rate (ADR), advancedneoplasia (AN) and CRC in the proximal and distal colon,histological and morphological characteristics in each section were analyzed.Results: in the study, 52.9 % of the patients were male, witha mean age of 59.5 years (standard deviation [SD]: 7.6);1,490 polyps were found and the ADR was 57.7 % (distal42 % and proximal 37 %). Detection rates were 45.8 % forAN, 40.9 % for advanced adenomas, 5.2 % for advancedsessile serrated lesions (SSL) and CRC was diagnosed in4.8 % of patients. Males had more AN than females. Themean age of patients with AN was significantly higher. ANwere associated with smoking and alcohol consumption (p = 0.0001). Globally, FIT levels were higher in patientswith AN (p = 0.003). Sixty-six per cent of cancers were distally located and 61.3 % of CRC were diagnosed in the earlystages.Conclusions: in an average-risk asymptomatic populationundergoing colonoscopy after positive FIT, AN were morecommon in the distal colon in males, older patients, smokers and those with alcohol intake. (AU)


Subject(s)
Humans , Colonoscopy , Colorectal Neoplasms , Tobacco Use Disorder , Alcohol Drinking
15.
United European Gastroenterol J ; 10(9): 1008-1019, 2022 11.
Article in English | MEDLINE | ID: mdl-36300971

ABSTRACT

BACKGROUND AND OBJECTIVE: Different factors may influence colonoscopy performance measures. We aimed to analyze procedure- and endoscopist-related factors associated with detection of colorectal lesions and whether these factors have a similar influence in the context of different colonoscopy indications: positive fecal immunochemical test (+FIT) and post-polypectomy surveillance colonoscopies. METHODS: This multicenter cross-sectional study included adults aged 40-80 years. Endoscopists (N = 96) who had performed ≥50 examinations were assessed for physician-related factors. Adenoma detection rate (ADR), adenomas per colonoscopy rate (APCR), advanced ADR, serrated polyp detection (SDR), and serrated polyps per colonoscopy rate (SPPCR) were calculated. RESULTS: We included 12,932 procedures, with 4810 carried out after a positive FIT and 1967 for surveillance. Of the 96 endoscopists evaluated, 43.8% were women, and the mean age was 41.9 years. The ADR, advanced ADR, and SDR were 39.7%, 17.7%, and 12.8%, respectively. Adenoma detection rate was higher in colonoscopies after a +FIT (50.3%) with a more than doubled advanced ADR compared to non-FIT procedures (27.6% vs. 13.0%) and similar results in serrated lesions (14.7% vs. 13.5%). Among all the detection indicators analyzed, withdrawal time was the only factor independently related to improvement (p < 0.001). Regarding FIT-positive and surveillance procedures, for both indications, withdrawal time was also the only factor associated with a higher detection of adenomas and serrated polyps (p < 0.001). Endoscopist-related factors (i.e., weekly hours dedicated to endoscopy, annual colonoscopy volume and lifetime number of colonoscopies performed) had also impact on lesion detection (APCR, advanced ADR and SPPCR). CONCLUSIONS: Withdrawal time was the factor most commonly associated with improved detection of colonic lesions globally and in endoscopies for + FIT and post-polypectomy surveillance. Physician-related factors may help to address strategies to support training and service provision. Our results can be used for establishing future benchmarking and quality improvement in different colonoscopy indications.


Subject(s)
Adenoma , Female , Humans , Adult , Male , Cross-Sectional Studies , Adenoma/diagnosis
16.
J Phys Condens Matter ; 34(29)2022 05 18.
Article in English | MEDLINE | ID: mdl-35504274

ABSTRACT

Herein, we report a computational investigation of the binding affinity of dexamethasone, betamethasone, chloroquine and hydroxychloroquine to SARS-CoV-2 main protease using molecular and quantum mechanics as well as molecular docking methodologies. We aim to provide information on the anti-COVID-19 mechanism of the abovementioned potential drugs against SARS-CoV-2 coronavirus. Hence, the 6w63 structure of the SARS-CoV-2 main protease was selected as potential target site for the docking analysis. The study includes an initial conformational analysis of dexamethasone, betamethasone, chloroquine and hydroxychloroquine. For the most stable conformers, a spectroscopic analysis has been carried out. In addition, global and local reactivity indexes have been calculated to predict the chemical reactivity of these molecules. The molecular docking results indicate that dexamethasone and betamethasone have a higher affinity than chloroquine and hydroxychloroquine for their theoretical 6w63 target. Additionally, dexamethasone and betamethasone show a hydrogen bond with the His41 residue of the 6w63 protein, while the interaction between chloroquine and hydroxychloroquine with this amino acid is weak. Thus, we confirm the importance of His41 amino acid as a target to inhibit the SARS-CoV-2 Mpro activity.


Subject(s)
COVID-19 Drug Treatment , SARS-CoV-2 , Amino Acids , Betamethasone , Chloroquine/chemistry , Chloroquine/pharmacology , Coronavirus 3C Proteases , Dexamethasone/pharmacology , Humans , Hydroxychloroquine/chemistry , Hydroxychloroquine/pharmacology , Molecular Docking Simulation , Molecular Dynamics Simulation , Protease Inhibitors/pharmacology
17.
Rev Esp Enferm Dig ; 114(12): 719-724, 2022 12.
Article in English | MEDLINE | ID: mdl-35285657

ABSTRACT

BACKGROUND: Colonoscopy is the gold standard method for the early diagnosis and prevention of colorectal cancer (CRC). Screening programs include immune determination of blood in feces. Regardless of the method used, proximal colon lesions appear to be detected less frequently. OBJECTIVE: Analyze the characteristics of proximal and distal lesions and possible predisposing factors. METHODS: A cross-sectional study was performed of 692 patients from the CRC screening program with FIT ≥ 100ngHb/ml (October 2017 - October 2018). The right colon was examined twice as patients were participating in a randomized clinical trial to re-evaluate the right colon by forward-viewing endoscope or proximal retroflexion. The adenoma detection rate (ADR), advanced neoplasia (AN) and CRC in the proximal and distal colon, the histological and morphological characteristics in each section were analyzed. RESULTS: 52.9% of the patients were male, with a mean age of 59.5 years (SD: 7.6). 1490 polyps were found and the ADR was 57.7% (distal 42% and proximal 37%). Detection rates were 45.8% for AN, 40.9% for advanced adenomas, 5.2% for advanced SSL and CRC was diagnosed in 4.8% of patients. Males had more AN than females. The mean age of patients with AN was significantly higher. AN were associated with smoking and alcohol consumption (p=0.0001). Globally, FIT levels were higher in patients with AN (p=0.003). Sixty-six per cent of cancers were distally located and 61.3% of CRC were diagnosed in the early stages. CONCLUSIONS: In an average-risk asymptomatic population undergoing colonoscopy after positive FIT, AN were more common in the distal colon in males, older patients, smokers and those with alcohol intake.


Subject(s)
Colorectal Neoplasms , Polyps , Female , Humans , Male , Middle Aged , Cross-Sectional Studies , Colonoscopy , Colorectal Neoplasms/diagnosis , Early Detection of Cancer/methods , Mass Screening/methods
18.
Dig Endosc ; 34(6): 1176-1184, 2022 Sep.
Article in English | MEDLINE | ID: mdl-35189669

ABSTRACT

OBJECTIVES: When bowel preparation (BP) is inadequate, international guidelines recommend repeating the colonoscopy within 1 year to avoid missing clinically relevant lesions. We aimed to determine the rate of missed lesions in patients with inadequate BP through a very early repeat colonoscopy with adequate BP. METHODS: Post hoc analysis was conducted using data collected from a prospective multicenter randomized clinical trial including patients with inadequate BP and then repeat colonoscopy. Inadequate BP was defined as the Boston Bowel Preparation Scale (BBPS) score <2 points in any segment. We included patients with any indication for colonoscopy. The adenoma detection rate (ADR), advanced ADR (AADR), and serrated polyp detection rate (SPDR) were calculated for index and repeat colonoscopies. RESULTS: Of the 651 patients with inadequate BP from the original trial, 413 (63.4%) achieved adequate BP on repeat colonoscopy. The median interval between index and repeat colonoscopies was 28 days. On repeat colonoscopy, the ADR was 45.3% (95% confidence interval [CI] 40.5-50.1%), the AADR was 10.9% (95% CI 8.1-14.3%), and the SPDR was 14.3% (95% CI 10.9-17.7%). Cancer was discovered in four patients (1%; 95% CI 0.2-2.5%). A total of 60.2% of all advanced adenoma (AA) were discovered on repeat colonoscopy. A colon segment scored BBPS = 0 had most AA (66.1%) and all four cancers. CONCLUSION: Patients with inadequate BP present a high rate of AAs on repeat colonoscopy. When a colonoscopy has a colon segment score BBPS = 0, we recommend repeating the colonoscopy as soon as possible.


Subject(s)
Adenoma , Colonic Polyps , Adenoma/diagnosis , Cathartics , Colonic Polyps/diagnosis , Colonic Polyps/pathology , Colonoscopy , Humans , Prevalence , Prospective Studies
20.
Endoscopy ; 54(1): 35-44, 2022 01.
Article in English | MEDLINE | ID: mdl-33264811

ABSTRACT

BACKGROUND: Resection techniques for small polyps include cold snare polypectomy (CSP) and hot snare polypectomy (HSP). This study compared CSP and HSP in 5-9 mm polyps in terms of complete resection and adverse events. METHODS: This was a multicenter, randomized trial conducted in seven Spanish centers between February and November 2019. Patients with ≥ 1 5-9 mm polyp were randomized to CSP or HSP, regardless of morphology or pit pattern. After polypectomy, two marginal biopsies were submitted to a pathologist who was blinded to polyp histology. Complete resection was defined as normal mucosa or burn artifacts in the biopsies. Abdominal pain was only assessed in patients without < 5 mm or > 9 mm polyps. RESULTS: 496 patients were randomized: 237 (394 polyps) to CSP and 259 (397 polyps) to HSP. Complete polypectomy rates were 92.5 % with CSP and 94.0 % with HSP (difference 1.5 %, 95 % confidence interval -1.9 % to 4.9 %). Intraprocedural bleeding occurred during three CSPs (0.8 %) and seven HSPs (1.8 %) (P = 0.34). One lesion per group (0.4 %) presented delayed hemorrhage. Post-colonoscopy abdominal pain presented similarly in both groups 1 hour after the procedure (CSP 18.8 % vs. HSP 18.4 %) but was higher in the HSP group after 5 hours (5.9 % vs. 16.5 %; P = 0.02). A higher proportion of patients were asymptomatic 24 hours after CSP than after HSP (97 % vs. 86.4 %; P = 0.01). CONCLUSIONS: We observed no differences in complete resection and bleeding rates between CSP and HSP. CSP reduced the intensity and duration of post-colonoscopy abdominal pain.


Subject(s)
Colonic Polyps , Biopsy , Colonic Polyps/surgery , Colonoscopy/adverse effects , Electrocoagulation , Humans
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