Guía de práctica clínica para la prevención primaria y secundaria y diagnóstico temprano de cáncer gástrico / Clinical practice guide for primary and secondary prevention and early diagnosis of gastric cancer

Resumen Objetivo: Generar recomendaciones basadas en la evidencia, para la prevención primaria y secundaria, el tratamiento de las lesiones preneoplásicas y el diagnóstico temprano del cáncer gástrico en población adulta, con el propósito de reducir la carga de la enfermedad. Materiales y métodos: El grupo desarrollador estuvo integrado por profesionales de la salud y tomadores de decisiones. Se construyeron preguntas clínicas contestables y se realizó la graduación de los desenlaces. Se elaboró la búsqueda de la información en MEDLINE; EMBASE y CENTRAL, siendo actualizada el 18 de octubre de 2018. La pesquisa también abarcó otras fuentes de información como la Revista Colombiana de Gastroenterología y la lectura en "bola de nieve" de las referencias incluidas. Se contactó a expertos en la materia con el objetivo de identificar estudios relevantes no publicados. Para la construcción de las recomendaciones, se realizó un consenso acorde con los lineamientos propuestos por la metodología GRADE, sopesando los beneficios, los efectos adversos derivados de la intervención, las preferencias de los pacientes y el potencial impacto de las intervenciones sobre los costos. Resultados: Se presenta la versión corta de la "Guía de práctica clínica para la prevención primaria, secundaria y diagnóstico temprano de cáncer gástrico", junto con su evidencia de soporte y respectivas recomendaciones. Conclusiones: Como recomendación central para la implementación, se recomienda erradicar la infección por H. pylori en los pacientes con o sin factores de riesgo, como estrategia de prevención de las condiciones precursoras de cáncer gástrico. La Guía deberá actualizarse en tres años.

Abstract Objetive: Generate recommendations for primary and secondary prevention, treatment of gastric preneoplastic lesions, and early diagnosis of gastric cancer in the adult population, to increase the detection of gastric cancer in early stages. Material and methods: The developer group was made up of health professionals, decision-makers, and a representative of the patients. Answerable clinical questions were constructed and outcomes were graded. The search for information in MEDLINE was carried out; EMBASE and CENTRAL, being updated on October 18, 2018. The search also covered other sources of information such as the Colombian Journal of Gastroenterology and the "snowball" reading of the references included. Experts in the field were contacted to identify studies. For the construction of the recommendations, a consensus was made according to the guidelines proposed by the GRADE methodology, weighing the benefits, the adverse effects derived from the intervention, the preferences of the patients, and the potential impact of the interventions on costs. Results: The short version of the "Clinical practice guidelines for the primary, secondary, and early diagnosis of gastric cancer" is presented together with its supporting evidence and respective recommendations. Conclusions: As a central recommendation for implementation, it is recommended to eradicate H. pylori infection in patients with or without risk factors in whom it is detected to prevent gastric cancer precursor conditions. The Guide will need to be updated in three years.

Cervical cancer screening programme attendance and compliance predictors regarding Colombia's Amazon region.

BACKGROUND: Cervical cancer (CC) promotion and prevention (P&P) programmes' challenge lies in guaranteeing that follow-up strategies have a real impact on reducing CC-related mortality rates. CC P&P programme compliance and coverage rates are relevant indicators for evaluating their success and good performance; however, such indicators' frequency rates are considerably lower among women living in rural and border areas. This study was aimed at identifying factors associated with CC screening programme attendance for women living in Colombia's Amazon region. METHODS: This study (qualitative and quantitative phases) was carried out between September 2015 and November 2016; women residing in the border towns of Leticia and Puerto Nariño participated in it. The first phase (qualitative) involved interviews and focus group discussions; this led to establishing factors related to CC P&P programme attendance which were used in the quantitative phase for designing a survey for determining the strength of association in a logistic regression model. The terms attendance and compliance were considered to apply to women who had followed the 1-1-3 scheme throughout their lives, i.e. a cytology examination every 3 years after receiving two consecutive negative annual cytology results. RESULTS: Inclusion criteria were met by 309 women (≥18-year-olds having an active sexual life, having resided in the target community for at least one year); 15.2% had suitable P&P programme follow-up. Screening programme attendance was positively associated with first intercourse after becoming 20 years-old (aOR: 3.87; 1.03-9.50 95%CI; p = 0.045), frequent contraceptive use (aOR: 3.11; 1.16-8.33 95%CI; p = 0.023), awareness of the age to participate in P&P programmes (aOR: 2.69; 1.08-6.68 95%CI; p = 0.032), awareness of cytology's usefulness in identifying cervical abnormalities (aOR: 2.43; 1.02-5.77 95%CI; p = 0.043) and considering cytology important (aOR: 2.64; 1.12-6.19 95%CI; p = 0.025). Women living in rural areas had a lower probability (aOR 0.43: 0.24-0.79 95%CI; p = 0.006) of adhering to CC P&P programmes. CONCLUSIONS: This study's findings suggested the need for including novel strategies in screening programmes which will promote CC P&P activities going beyond hospital outpatient attendance to reach the most remote or widely scattered communities, having the same guarantees regarding access, opportunity and quality. Including education-related activities and stimulating the population's awareness regarding knowledge about CC prevention could be one of the main tools for furthering the impact of attendance at and compliance with P&P programmes.

Identifying HLA DRB1-DQB1 alleles associated with Chlamydia trachomatis infection and in silico prediction of potentially-related peptides.

HLA class II (HLA-II) genes' polymorphism influences the immune response to Chlamydia trachomatis (Ct), it is considered a sexually transmitted infection. However, associations between HLA-II alleles and Ct-infection have been little explored in humans; this study was thus aimed at determining HLA-DRB1-DQB1 alleles/haplotypes' effect on Ct-infection outcome in a cohort of Colombian women. Cervical sample DNA was used as template for detecting Ct by PCR and typing HLA-DRB1-DQB1 alleles/haplotypes by Illumina MiSeq sequencing. Survival models were adjusted for identifying the alleles/haplotypes' effect on Ct-outcome; bioinformatics tools were used for predicting secreted bacterial protein T- and B-cell epitopes. Sixteen HLA-DRB1 alleles having a significant effect on Ct-outcome were identified in the 262 women analysed. DRB1*08:02:01G and DRB1*12:01:01G were related to infection-promoting events. Only the DQB1*05:03:01G allele related to clearance/persistence events was found for HLA-DQB1. HLA-DRB1 allele homozygous women were associated with events having a lower probability of clearance and/or early occurrence of persistence. Twenty-seven peptides predicted in silico were associated with protective immunity against Ct; outer membrane and polymorphic membrane protein-derived peptides had regions having dual potential for being T- or B-cell epitopes. This article describes HLA-DRB1-DQB1 alleles/haplotypes related to Ct-infection resolution and the peptides predicted in silico which might probably be involved in host immune response. The data provides base information for developing future studies leading to the development of effective prevention measures against Ct-infection.

Identifying the HLA DRB1-DQB1 molecules and predicting epitopes associated with high-risk HPV infection clearance and redetection.

Several determining factors are involved in HPV infection outcomes; human leukocyte antigen (HLA) polymorphisms have been described as related factors. This study has ascertained the effect of genetic variation on HLA-DRB1 and DQB1 genes on HPV-16/-18/-31/-33/-45 and -58 clearance and redetection in Colombian women. PCR and qPCR were used for viral identification and the Illumina MiSeq system was used for HLA-typing of cervical samples (n = 276). Survival models were adjusted for identifying alleles/haplotypes related to HPV clearance/redetection; L1/L2 protein-epitope binding to MHC-II molecules was also predicted. Significant associations suggested effects favouring or hampering clearance/redetection events depending on the viral type involved in infection, e.g. just DRB1*12:01:01G favoured HPV-16 (coeff: 4.8) and HPV-45 clearance (coeff: 12.65) whilst HPV-18 (coeff: 2E-15), HPV-31 (coeff: 8E-17) and HPV-58 hindered elimination (coeff: 1E-14). An effect was only observed for some alelles when configured as haplotypes, e.g. DRB1*04:07:01G (having the greatest frequency in the target population) was associated with DQB1*02:01:1G or *03:02:03. Epitope prediction identified 23 clearance-related peptides and 29 were redetection-related; eight might have been related to HPV-16/-18 and -58 persistence and one to HPV-18 elimination. HLA allele/haplotype relationship with the course of HPV infection (clearance/redetection) depended on the infecting HPV type, in line with the specific viral epitopes displayed.

Using next-generation sequencing for characterising HLA-DRB1 and DQB1 loci in a cohort of Colombian women.

The Colombian population is characterised by a high genetic diversity, secondary to the ethnic mixture arising from colonisation. Unfortunately, few reports are available regarding HLA-DRB1 and DQB1 diversity in Colombia to date. HLA-DRB1 and DQB1 diversity was identified in this study using next-generating sequencing (NGS) on a cohort of Colombian women. Cervical samples taken from 276 women were used for typing DRB1 and DQB1 loci by Illumina MiSeq. Allele and haplotype frequencies were calculated using an expectation-maximisation algorithm. Hardy-Weinberg Equilibrium and linkage disequilibrium (LD) between loci were evaluated. Forty-seven DRB1 alleles and 14 DQB1 alleles were identified. DRB1*04:07:01G and DQB1*03:02:01G alleles occurred most frequently in the target population. Significant LD was found in 44 out of the 144 identified haplotypes, within which DRB1*04:07:01G-DQB1*03:02:01G occurred most frequently (6.56%). The alleles and haplotypes found with NGS agreed with that found in previous reports involving lower resolution for the Colombian population, and greater genetic variability was found, especially concerning DRB1. Comparing allele and haplotype frequency distribution in the target population to that of other populations denoted HLA system intra- and inter-population diversity.

Association of HIV status with infection by multiple HPV types.

OBJECTIVES: To identify the clinical and demographic characteristics of HIV-positive and HIV-negative women infected by multiple HPV types. METHODS: 1399 women participated in the study (240 HIV-positive and 1159 HIV-negative women). Samples were provided for Pap tests and for HPV detection and typing by PCR. Data were collected on HPV infection, frequency of multiple infection, and HPV type distribution. Odds ratios were reported from logistic regression models. RESULTS: Compared with HIV-negative women, HIV-positive women had higher frequencies of cervical abnormality (30% vs. 20.8%), higher HPV prevalence (68.3% vs. 51.3%) and were more commonly infected with multiple HPV types (78.7% vs. 44.3%). HPV-16 was the most common type detected in the study population, with other types showing variable associations with HIV status. Positive associations were observed between infection by multiple HPV types and HIV status, cervical abnormality and having had more than three pregnancies. The odds of multiple infection by HPV types were higher in HIV-positive women who used an intrauterine device, who had a history of abortions and who had HIV viral loads >100 000 copies/ml, whilst the odds were lower in women with >500 CD4 cells/mm3 . CONCLUSIONS: HIV immunosuppression favours infection by multiple high-risk HPV types, mainly in women affected by low-grade squamous intraepithelial lesions. Antiretroviral therapy had no effect on infection by multiple HPV types. Risk factors related to progressive damage to the cervix were positively associated with infection by multiple HPV types in women living with HIV.

Micro-epidemiology of mixed-species malaria infections in a rural population living in the Colombian Amazon region.

Malaria outbreaks have been reported in recent years in the Colombian Amazon region, malaria has been re-emerging in areas where it was previously controlled. Information from malaria transmission networks and knowledge about the population characteristics influencing the dispersal of parasite species is limited. This study aimed to determine the distribution patterns of Plasmodium vivax, P. malariae and P. falciparum single and mixed infections, as well as the significant socio-spatial groupings relating to the appearance of such infections. An active search in 57 localities resulted in 2,106 symptomatic patients being enrolled. Parasitaemia levels were assessed by optical microscopy, and parasites were detected by PCR. The association between mixed infections (in 43.2% of the population) and socio-spatial factors was modelled using logistic regression and multiple correspondence analyses. P. vivax occurred most frequently (71.0%), followed by P. malariae (43.2%), in all localities. The results suggest that a parasite density-dependent regulation model (with fever playing a central role) was appropriate for modelling the frequency of mixed species infections in this population. This study highlights the under-reporting of Plasmodium spp. mixed infections in the malaria-endemic area of the Colombian Amazon region and the association between causative and environmental factors in such areas.

The Prevalence of High-Risk HPV Types and Factors Determining Infection in Female Colombian Adolescents.

This study reports six HR-HPV types' infection prevalence discriminated by species and multiple infection in unvaccinated Colombian female adolescents, as well as some factors modulating the risk of infection. HPV DNA for six high-risk viral types was identified in cervical samples taken from 2,134 12-19 year-old females using conventional generic and type-specific PCR. Binomial logistical regression analysis was used for modelling HR-HPV infection and multiple infection risk. The interaction between variables in a stepwise model was also included in such analysis. Viral DNA was detected in 48.97% of the females; 28.52% of them had multiple infections, HPV-16 being the most frequently occurring type (37.44%). Cytological abnormality prevalence was 15.61%. Being over 16 years-old (1.66: 1.01-2.71 95%CI), white ethnicity (4.40: 1.16-16.73 95%CI), having had 3 or more sexual partners (1.77: 1.11-2.81 95%CI) and prior sexually-transmitted infections (STI) (1.65: 1.17-2.32 95%CI) were associated with a greater risk of HPV infection. Having given birth was related to a higher risk of infection by A7 species and antecedent of abortion to less risk of coinfection. Where the females in this study came from also influenced the risk of infection by A7 species as female adolescents from the Andean region had a lower risk of infection (0.42: 0.18-0.99 95%CI). The presence of factors related to risky sexual behaviour in the study population indicated that public health services should pay special attention to female adolescents to modify the risk of infection by high-risk HPV types and decrease their impact on this age group.

Chlamydia trachomatis Frequency in a Cohort of HPV-Infected Colombian Women.

BACKGROUND: Chlamydia trachomatis (C. trachomatis), an obligate intracellular bacterium, is the commonest infectious bacterial agent of sexual transmission throughout the world. It has been shown that the presence of this bacteria in the cervix represents a risk regarding HPV persistence and, thereafter, in developing cervical cancer (CC). Prevalence rates may vary from 2% to 17% in asymptomatic females, depending on the population being analysed. This study reports the identification of C. trachomatis in a cohort of 219 HPV-infected Colombian females. METHODS: C. trachomatis infection frequency was determined during each of the study's follow-up visits; it was detected by amplifying the cryptic plasmid sequence by polymerase chain reaction (PCR) using two sets of primers: KL5/KL6 and KL1/KL2. Infection was defined as a positive PCR result using either set of primers at any time during the study. Cox proportional risk models were used for evaluating the association between the appearance of infection and a group of independent variables. RESULTS: Base line C. trachomatis infection frequency was 28% (n = 61). Most females infected by C. trachomatis were infected by multiple types of HPV (77.42%), greater prevalence occurring in females infected with HPV-16 (19.18%), followed by HPV-58 (17.81%). It was observed that females having had the most sexual partners (HR = 6.44: 1.59-26.05 95%CI) or infection with multiple types of HPV (HR = 2.85: 1.22-6.63 95%CI) had the greatest risk of developing C. trachomatis. CONCLUSIONS: The study provides data regarding the epidemiology of C. trachomatis /HPV coinfection in different population groups of Colombian females and contributes towards understanding the natural history of C. trachomatis infection.

The DNA load of six high-risk human papillomavirus types and its association with cervical lesions.

BACKGROUND: Analysing human papillomavirus (HPV) viral load is important in determining the risk of developing cervical cancer (CC); most knowledge to date regarding HPV viral load and cervical lesions has been related to HPV-16. This study evaluated the association between the viral load of the six most prevalent high-risk viral types in Colombia and cervical intraepithelial neoplasia (CIN) frequency. METHODS: 114 women without CIN and 59 women having CIN confirmed by colposcopy, all of them positive by conventional PCR for HPV infection in the initial screening, were included in the study. Samples were tested for six high-risk HPV types to determine viral copy number by real-time PCR. Crude and adjusted odds ratios (ORa) were estimated for evaluating the association between each viral type's DNA load and the risk of cervical lesions occurring. RESULTS: The highest viral loads were identified for HPV-33 in CIN patients and for HPV-31 in patients without lesions (9.33 HPV copies, 2.95 interquartile range (IQR); 9.41 HPV copies, 2.58 IQR). Lesions were more frequent in HPV-16 patients having a low viral load (3.53 ORa, 1.16-10.74 95%CI) compared to those having high HPV-16 load (2.62 ORa, 1.08-6.35 95%CI). High viral load in HPV-31 patients was associated with lower CIN frequency (0.34 ORa, 0.15-0.78 95%CI). CONCLUSIONS: An association between HPV DNA load and CIN frequency was seen to be type-specific and may have depended on the duration of infection. This analysis has provided information for understanding the effect of HPV DNA load on cervical lesion development.

Persistence, clearance and reinfection regarding six high risk human papillomavirus types in Colombian women: a follow-up study.

BACKGROUND: The design of new healthcare schemes which involve using molecular HPV screening means that both persistence and clearance data regarding the most prevalent types of HR-HPV occurring in cities in Colombia must be ascertained. METHODS: This study involved 219 HPV positive women in all of whom 6 types of HR-HPV had been molecularly identified and quantified; they were followed-up for 2 years. The Kaplan-Meier survival function was used for calculating the time taken for the clearance of each type of HPV. The role of a group of independent variables concerning the time taken until clearance was evaluated using a Cox proportional-hazards regression model or parametric (log-logistic) methods when necessary. Regarding viral load, the Wilcoxon rank-sum test was used for measuring the difference of medians for viral load for each type, according to the state of infection (cleared or persistent). The Kruskal-Wallis test was used for evaluating the change in the women's colposcopy findings at the start of follow-up and at the end of it (whether due to clearance or the end of the follow-up period). RESULTS: It was found that HPV-18 and HPV-31 types had the lowest probability of becoming cleared (1.76 and 2.75 per 100 patients/month rate, respectively). Women from Colombian cities other than Bogotá had a greater probability of being cleared if they had HPV-16 (HR 2.58: 1.51-4.4 95% CI) or HPV-58 (1.79 time ratio: 1.33-2.39 95% CI) infection. Regarding viral load, HPV-45-infected women having 1 × 106 to 9.99 × 109 viral copies had better clearance compared to those having greater viral loads (1.61 time ratio: 1.01-2.57 95% CI). Lower HPV-31 viral load values were associated with this type's persistence and changes in colposcopy findings for HPV-16 gave the worst prognosis in women having low absolute load values. CONCLUSIONS: HPV infection clearance in this study was related to factors such as infection type, viral load and the characteristics of the cities from which the women came. Low viral load values would indicate viral persistence and a worse prognosis regarding a change in colposcopy findings.

Efecto de cinco extractos de plantas colombianas sobre espermatozoides humanos / Effect of five Colombian plant extracts on human spermatozoids

Introducción: las pruebas de capacitación espermática y la actividad espermicida o inmovilizante usando extractos de plantas permiten incrementar los conocimientos actuales en el área reproductiva. Objetivos: evaluar el efecto de 5 extractos de las plantas colombianas Bocconia frutescens, Bomarea setaceas, Muehlenbeckia platyclada, Zanthoxylum lenticulare y Piper subpedale sobre los espermatozoides humanos. Métodos: los espermatozoides humanos se incubaron con los extractos de las plantas, se valoró su movilidad y viabilidad. Adicionalmente la capacitación espermática se evaluó utilizando albúmina sérica bovina. Resultados: después de una evaluación inicial del efecto de los extractos de las plantas sobre la movilidad o viabilidad de los espermatozoides, se seleccionaron los extractos de B. frutescens y B. setaceas para realizar los ensayos de capacitación espermática, porque no alteraron ni la movilidad ni la viabilidad espermática, y se seleccionaron los extractos de M. platyclada, Z. lenticulare y P. subpedale para los ensayos de actividad espermicida debido a que afectaron la movilidad progresiva espermática. Conclusiones: este trabajo permitió proponer 3 plantas con promisoria actividad espermicida, y se logró estandarizar un sistema biológico en el cual se pudo evaluar el efecto capacitante de algunos extractos sobre los espermatozoides humanos.

Introduction: the sperm capacitation test and the spermicidal activity or immobilization using plant extracts, allows for an increase in the current knowledge on the reproductive area. Objectives: to evaluate the effect of five extracts from Colombian plants Bocconia frutescens, Bomarea setaceas, Muehlenbeckia platyclada, Zanthoxylum lenticulare and Piper subpedale on human spermatozoa. Methods: human spermatozoa were incubated with each extract and their motility and viability were evaluated. Additionally, sperm capacitation was evaluated using bovine serum albumin. Results: after an initial assessment of the effect of plant extracts on human spermatozoa, the extracts from B. frutescens and B. setaceas were selected for capacitating tests since they did not change the sperm motility and viability. Additionally, M. platyclada, Z. lenticulare and P. subpedale extracts were selected for immobilization or spermicidal activities tests because they had had an effect on sperm progressive motility. Conclusions: this study suggested three plants with promising spermicidal effect; in addition to the standardization of a biological system, allowing the assessment of the capacitation effect of some extracts over human spermatozoa.

Infarto agudo del miocardio en adultos jóvenes menores de 45 años / Acute heart attack of the myocardium in 45-year-old adult minor young men

Estudios realizados en distintas poblaciones, indican que existe asociación entre los factores de riesgo principales para enfermedad coronaria arterioesclerótica como causa directa de la aparición de síndrome coronario agudo (SCA), específicamente infarto agudo del miocardio (IAM), en sujetos mayores de 45 años. En la población menor de 45 años esta entidad suele relacionarse con mayor frecuencia, a fenómenos de hipercoagulabilidad, vasculitis, vasoespasmo endógeno o vasoespasmo mediado por sustancias tóxicas; subestimando o sin considerar los factores de riesgo principales para la enfermedad coronaria como génesis directa de causalidad en esta población.Objetivo: describir las características clínicas y los factores de riesgo de los pacientes menores de 45 años con diagnóstico de infarto agudo del miocardio.Diseño: estudio observacional descriptivo de corte transversal; retrospectivo.