Immune microenvironment of cervical cancer and the role of IL-2 in tumor promotion.

The tumor microenvironment (TME) is a heterogeneous mixture of resident and tumor cells that maintain close communication through their secretion products. The composition of the TME is dynamic and complex among the different types of cancer, where the immune cells play a relevant role in the elimination of tumor cells, however, under certain circumstances they contribute to tumor development. In cervical cancer (CC) the human papilloma virus (HPV) shapes the microenvironment in order to mediate persistent infections that favors transformation and tumor development. Interleukin-2 (IL-2) is an important TME cytokine that induces CD8+ effector T cells and NKs to eliminate tumor cells, however, IL-2 can also suppress the immune response through Treg cells. Recent studies have shown that CC cells express the IL-2 receptor (IL-2R), that are induced to proliferate at low concentrations of exogenous IL-2 through alterations in the JAK/STAT pathway. This review provides an overview of the main immune cells that make up the TME in CC, as well as the participation of IL-2 in the tumor promotion. Finally, it is proposed that the low density of IL-2 produced by immunocompetent cells is used by tumor cells through its IL-2R as a mechanism to proliferate simultaneously depleting this molecule in order to evade immune response.

Comparison of Whole-Body Dosimetry Measurements in 131I Therapy Using Ceiling-Mounted Geiger-Müller Detectors and γ-Camera Scans: An Agreement Analysis.

Background: In 131I therapies internal dosimetry is crucial for determining the mean absorbed dose to organs at risk, particularly the bone marrow, which has a dose constraint of 2 Gy. Traditionally, multicompartmental models have been used for bone marrow dosimetry, necessitating whole-body absorbed-dose assessments. However, noninvasive techniques, such as γ-camera scans or ceiling-mounted Geiger-Müller (GM) counters, can estimate the aforementioned. This study was aimed to evaluate the agreement between whole-body mean absorbed dose using γ-camera scans and ceiling-mounted GM in patients with thyroid carcinoma undergoing 131I therapy. Methods: This study included 31 patients with thyroid cancer who were treated with 131I. The whole-body time-integrated activity (TIA) and mean absorbed dose were estimated using the elimination curves obtained with γ-camera scans and ceiling-mounted GM. In addition, statistical analysis was performed on the data to determine the Coefficient Correlation Coefficient and the Bland-Altman limits of agreement for both parameters, as well as for the elimination curves' effective half-life. Results: The study revealed correlations of 0.562 and 0.586 between whole-body TIA and mean absorbed dose, respectively. The Bland-Altman limits of agreement were found to be below -3.75% and within 12.75% of the bone marrow dose constraint of 2 Gy. The nonparametric evaluation revealed that whole-body TIA and mean absorbed dose medians from GM were lower than those from γ-camera scans (p < 0.001). Effective half-life estimation mean was significantly lower in the GM than in the γ-camera of 13 and 23 h. Conclusions: Although GM calculates the whole-body absorbed dose with margins of error within clinical acceptance, underestimation of the effective half-life makes it an unacceptable substitute method for γ-cameras in clinical practice. Further research should be conducted to evaluate single-point GM measurement substitutions in time-activity curves.

Development and Evaluation of an Enzyme-Linked Immunosorbent Assay Targeting Rabies-Specific IgM and IgG in Human Sera.

Immunity from rabies depends on rabies virus neutralizing antibodies (RVNA) induced after immunization; however, the influence of antibody isotype switching has not been extensively investigated. This has become particularly relevant with changes in World Health Organization (WHO) recommended rabies vaccine regimens that may influence RVNA isotype kinetics, potentially affecting the peak, and longevity, of RVNA immunoglobulin (IgG) levels. We developed rapid and reliable assays for quantifying the anti-rabies IgM/IgG class switch in human serum based on an indirect ELISA technique. The immune response was tracked in ten individuals naïve to the rabies vaccine by quantifying serum titers weekly, from day seven to day 42 post-immunization, using a serum neutralization assay and the ELISA IgM/IgG assays. The average RVNA IU/mL levels were at D0 ≤ 0.1, D7 0.24, D14 8.36, D21 12.84, D28 25.74 and D42 28.68. Levels of specific IgM antibodies to rabies glycoprotein (EU/mL) were higher, on average, at D7, 1.37, and from D14, 5.49, to D21, 6.59. In contrast, average IgG antibodies (EU/mL) predominated from D28, 10.03, to D42, 14.45. We conclude that levels of anti-rabies IgM/IgG at D28 characterize the isotype class switch. These assays, combined with serum neutralization assays, distinguished the RVNA levels in terms of the IgM/IgG responses and are expected to add to the diagnostic repertoire, provide additional information in establishing rabies vaccine regimens, both post- and pre-exposure prophylaxis, and contribute to research efforts.

Consensus for the treatment of upper urinary tract infections during pregnancy / Consenso para el tratamiento de la infección de vías urinarias altas durante la gestación

Objectives: To generate evidence-based recommendations through formal consensus regarding the treatment of upper urinary tract infections during gestation. Materials and methods: Experts in microbiology, public health, internal medicine, infectious diseases, obstetrics, maternal fetal medicine and obstetric and gynecological infections participated in the consensus development group. The group also included professionals with training in clinical epidemiology, systematic data search, and representatives from the Health Secretariat and the Bogota Obstetrics and Gynecology Association. The participants disclosed their conflicts of interest. Starting with a clinical question, outcomes were graded and a systematic search was conducted in the Medline via PubMed, Embase, Lilacs, and Bireme databases. The search was expanded to include institutional repositories and antimicrobial resistance surveillance systems, with no language or date restrictions. The search was updated on October 1, 2022. The GRADE (Grading of Recommendations Assessment, Development and Evaluation) methodology was used to assess the quality of the evidence and determine the strength of the recommendations. Finally, the RAND/UCLA (Research and Development/University of California Los Angeles) methodology was applied for the formal consensus. This document was reviewed by academic peers before publication. Results: The following are the consensus recommendations. Recommendation 1. The initial management of pregnant women with upper urinary tract infections (UTIs) should be approached in a hospital setting. Recommendation 2. The use of second generation cephalosporins is the suggested first option for empirical antimicrobial management in pregnant women with upper UTI in order to improve the rates of clinical and microbiological cure. Recommendation 3. Because of the risk-benefit balance, the use of aminoglycosides is suggested as a second option for empirical antimicrobial treatment in pregnant women presenting with upper UTIs in the second and third trimester. Recommendation 4. The use of third-generation cephalosporins is suggested as the third option for empirical antimicrobial treatment in pregnant women with upper UTIs given that the risk of inducing microbial resistance is high with this group of antibiotics. Recommendation 5. The use of carbapenems is suggested as a first option in pregnant women with upper UTIs and a history of infections caused by microorganisms with resistance to third or fourth-generation cephalosporins. Recommendation 6. The use of aminoglycosides or fourth-generation cephalosporins is suggested as a second option in pregnant women with upper UTIs and a history of infection caused by microorganisms with resistance to third-generation cephalosporins, taking risk-benefit into account. Recommendation 7. The use of piperacillin/tazobactam is suggested as a third option in pregnant women with upper UTIs and a history of infection caused by microorganisms with resistance to third or fourthgeneration cephalosporins. Recommendation 8. Getting a urine culture is recommended in pregnant women with upper UTIs before initiating empirical antimicrobial treatment. Recommendation 9. In pregnant women with upper UTIs, it is suggested to modify therapy in accordance with the results of the sensitivity test when the culture report shows resistance to the antimicrobial agent initiated empirically. Recommendation 10. In pregnant women hospitalized due to upper UTIs, it is suggested to switch to oral antimicrobial therapy after at least 48 hours of modulation of the systemic inflammatory response and the clinical signs of infection, and when tolerance to oral intake is adequate. Recommendation 11. In pregnant women with upper UTIs with no complications secondary to the primary infection, it is recommended to administer antibiotic therapy for a period of 7 to 10 days. Conclusions: It is expected that with this Colombian upper UTI consensus variability in clinical practice will be reduced. It is recommended that groups doing research in maternal fetal medicine assess the implementation and effectiveness of these recommendations.

Objetivos: generar recomendaciones informadas en la evidencia, a través de un consenso formal, orientadas al tratamiento de la infección de vías urinarias altas durante la gestación. Materiales y métodos: en el grupo desarrollador participaron expertos temáticos en microbiología, salud pública, medicina interna, infectología, obstetricia, medicina materno-fetal e infectología ginecobstétrica. También hicieron parte profesionales con entrenamiento en epidemiología clínica, búsqueda sistemática de la información, representantes de la Secretaría de Salud y la Asociación Bogotana de Obstetricia y Ginecología. Los participantes presentaron sus conflictos de interés. A partir de una pregunta clínica se realizó la graduación de los desenlaces y una búsqueda sistemática que abarcó las bases de datos Medline vía PubMed, Embase, Lilacs, Bireme. La pesquisa se amplió a repositorios institucionales y reportes de vigilancia de resistencia antimicrobiana, sin restricción de idioma o fecha, la búsqueda se actualizó el 1 de octubre de 2022. Se utilizó la metodología GRADE (Grading of Recommendations Assessment, Development and Evaluation) para valorar la calidad de la evidencia y establecer la fuerza de las recomendaciones.Finalmente, se utilizó la metodología RAND/ UCLA (Research and Development/University of California Los Angeles) para el consenso formal. Este documento fue revisado por pares académicos previo a su publicación. Resultados: el consenso formuló las siguientes recomendaciones. Recomendación 1. Se sugiere que el manejo inicial de la gestante con infección de vías urinarias (IVU) altas se realice de forma intrahospitalaria. Recomendación 2. Como primera opción, se sugiere que el tratamiento antimicrobiano empírico de la gestante con IVU altas se realice con el uso de cefalosporinas de segunda generación con el fin de mejorar la tasa de cura clínica y microbiológica. Recomendación 3. Como segunda opción, se sugiere que el tratamiento antimicrobiano empírico de la gestante con IVU altas en el segundo y tercer trimestre se realice con aminoglucósidos dado su balance riesgo-beneficio. Recomendación 4. Como tercera opción, se sugiere que el tratamiento antimicrobiano empírico de la gestante con IVU altas se realice con el uso de cefalosporinas de tercera generación, debido a que el riesgo de inducción de resistencia microbiana es alto con este grupo de antibióticos. Recomendación 5. Como primera opción, en mujeres gestantes con IVU altas y antecedente de infección por microorganismos con resistencia a cefalosporinas de tercera o cuarta generación se sugiere el uso de carbapenémicos. Recomendación 6. Como segunda opción, en gestantes con IVU altas y antecedente de infección por microorganismos con resistencia a cefalosporinas de tercera generación se sugiere el uso de aminoglucósidos o cefalosporinas de cuarta generación teniendo en cuenta el riesgo-beneficio. Recomendación 7. Como tercera opción, en gestantes con IVU altas y antecedente de infección por microorganismos con resistencia a cefalosporinas de tercera o cuarta generación se sugiere el uso de piperacilina/tazobactam. Recomendación 8. En gestantes con IVU altas se recomienda realizar urocultivo previo al inicio de tratamiento antimicrobiano empírico. Recomendación 9. En gestantes con IVU altas, cuando el urocultivo reporte resistencia al antimicrobiano iniciado de forma empírica, se sugiere modificar la terapia guiada por los resultados del antibiograma. Recomendación 10. En la gestante hospitalizada por IVU altas se sugiere realizar el cambio de terapia antimicrobiana a vía oral cuando la paciente tenga, al menos, 48 horas de modulación de respuesta inflamatoria sistémica y de los signos clínicos de infección, así como adecuada tolerancia a vía oral. Recomendación 11. En gestantes con IVU altas, sin complicaciones secundarias a la infección primaria, se recomienda que la terapia antibiótica se administre de 7 a 10 días. Conclusiones: se espera que este consenso colombiano de IVU altas reduzca la variabilidad en la práctica clínica. Se recomienda a los grupos de investigación en medicina materno fetal e infectología evaluar la implementación y efectividad de las recomendaciones emitidas.

Consenso para el tratamiento de la infección de vías urinarias altas durante la gestación / Consensus for the treatment of upper urinary tract infections during pregnancy

Objetivos: Generar recomendaciones informadas en la evidencia, a través de un consenso formal, orientadas al tratamiento de la infección de vías urinarias altas durante la gestación. Materiales y métodos: En el grupo desarrollador participaron expertos temáticos en microbiología, salud pública, medicina interna, infectología, obstetricia, medicina materno-fetal e infectología ginecobstétrica. También hicieron parte profesionales con entrenamiento en epidemiología clínica, búsqueda sistemática de la información, representantes de la Secretaría de Salud y la Asociación Bogotana de Obstetricia y Ginecología. Los participantes presentaron sus conflictos de interés. A partir de una pregunta clínica se realizó la graduación de los desenlaces y una búsqueda sistemática que abarcó las bases de datos Medline vía PubMed, Embase, Lilacs, Bireme. La pesquisa se amplió a repositorios institucionales y reportes de vigilancia de resistencia antimicrobiana, sin restricción de idioma o fecha, la búsqueda se actualizó el 1 de octubre de 2022. Se utilizó la metodología GRADE (Grading of Recommendations Assessment, Development and Evaluation) para valorar la calidad de la evidencia y establecer la fuerza de las recomendaciones. Finalmente, se utilizó la metodología RAND/ UCLA (Research and Development/University of California Los Angeles) para el consenso formal. Este documento fue revisado por pares académicos previo a su publicación. Resultados: El consenso formuló las siguientes recomendaciones. Recomendación 1. Se sugiere que el manejo inicial de la gestante con infección de vías urinarias (IVU) altas se realice de forma intrahospitalaria. Recomendación 2. Como primera opción, se sugiere que el tratamiento antimicrobiano empírico de la gestante con IVU altas se realice con el uso de cefalosporinas de segunda generación con el fin de mejorar la tasa de cura clínica y microbiológica. Recomendación 3. Como segunda opción, se sugiere que el tratamiento antimicrobiano empírico de la gestante con IVU altas en el segundo y tercer trimestre se realice con aminoglucósidos dado su balance riesgo-beneficio. Recomendación 4. Como tercera opción, se sugiere que el tratamiento antimicrobiano empírico de la gestante con IVU altas se realice con el uso de cefalosporinas de tercera generación, debido a que el riesgo de inducción de resistencia microbiana es alto con este grupo de antibióticos. Recomendación 5. Como primera opción, en mujeres gestantes con IVU altas y antecedente de infección por microorganismos con resistencia a cefalosporinas de tercera o cuarta generación se sugiere el uso de carbapenémicos. Recomendación 6. Como segunda opción, en gestantes con IVU altas y antecedente de infección por microorganismos con resistencia a cefalosporinas de tercera generación se sugiere el uso de aminoglucósidos o cefalosporinas de cuarta generación teniendo en cuenta el riesgo-beneficio. Recomendación 7. Como tercera opción, en gestantes con IVU altas y antecedente de infección por microorganismos con resistencia a cefalosporinas de tercera o cuarta generación se sugiere el uso de piperacilina/tazobactam. Recomendación 8. En gestantes con IVU altas se recomienda realizar urocultivo previo al inicio de tratamiento antimicrobiano empírico. Recomendación 9. En gestantes con IVU altas, cuando el urocultivo reporte resistencia al antimicrobiano iniciado de forma empírica, se sugiere modificar la terapia guiada por los resultados del antibiograma. Recomendación 10. En la gestante hospitalizada por IVU altas se sugiere realizar el cambio de terapia antimicrobiana a vía oral cuando la paciente tenga, al menos, 48 horas de modulación de respuesta inflamatoria sistémica y de los signos clínicos de infección, así como adecuada tolerancia a vía oral. Recomendación 11. En gestantes con IVU altas, sin complicaciones secundarias a la infección primaria, se recomienda que la terapia antibiótica se administre de 7 a 10 días. Conclusiones: se espera que este consenso colombiano de IVU altas reduzca la variabilidad en la práctica clínica. Se recomienda a los grupos de investigación en medicina materno fetal e infectología evaluar la implementación y efectividad de las recomendaciones emitidas.

Objectives: To generate evidence-based recommendations through formal consensus regarding the treatment of upper urinary tract infections during gestation. Materials and methods: Experts in microbiology, public health, internal medicine, infectious diseases, obstetrics, maternal fetal medicine and obstetric and gynecological infections participated in the consensus development group. The group also included professionals with training in clinical epidemiology, systematic data search, and representatives from the Health Secretariat and the Bogota Obstetrics and Gynecology Association. The participants disclosed their conf licts of interest. Starting with a clinical question, outcomes were graded and a systematic search was conducted in the Medline via PubMed, Embase, Lilacs, and Bireme databases. The search was expanded to include institutional repositories and antimicrobial resistance surveillance systems, with no language or date restrictions. The search was updated on October 1, 2022. The GRADE (Grading of Recommendations Assessment, Development and Evaluation) methodology was used to assess the quality of the evidence and determine the strength of the recommendations. Finally, the RAND/UCLA (Research and Development/University of California Los Angeles) methodology was applied for the formal consensus. This document was reviewed by academic peers before publication. Results: The following are the consensus recommendations. Recommendation 1. The initial management of pregnant women with upper urinary tract infections (UTIs) should be approached in a hospital setting. Recommendation 2. The use of second generation cephalosporins is the suggested first option for empirical antimicrobial management in pregnant women with upper UTI in order to improve the rates of clinical and microbiological cure. Recommendation 3. Because of the risk-benefit balance, the use of aminoglycosides is suggested as a second option for empirical antimicrobial treatment in pregnant women presenting with upper UTIs in the second and third trimester. Recommendation 4. The use of third-generation cephalosporins is suggested as the third option for empirical antimicrobial treatment in pregnant women with upper UTIs given that the risk of inducing microbial resistance is high with this group of antibiotics. Recommendation 5. The use of carbapenems is suggested as a first option in pregnant women with upper UTIs and a history of infections caused by microorganisms with resistance to third or fourth-generation cephalosporins. Recommendation 6. The use of aminoglycosides or fourth-generation cephalosporins is suggested as a second option in pregnant women with upper UTIs and a history of infection caused by microorganisms with resistance to third-generation cephalosporins, taking risk-benefit into account. Recommendation 7. The use of piperacillin/tazobactam is suggested as a third option in pregnant women with upper UTIs and a history of infection caused by microorganisms with resistance to third or fourth-generation cephalosporins. Recommendation 8. Getting a urine culture is recommended in pregnant women with upper UTIs before initiating empirical antimicrobial treatment. Recommendation 9. In pregnant women with upper UTIs, it is suggested to modify therapy in accordance with the results of the sensitivity test when the culture report shows resistance to the antimicrobial agent initiated empirically. Recommendation 10. In pregnant women hospitalized due to upper UTIs, it is suggested to switch to oral antimicrobial therapy after at least 48 hours of modulation of the systemic inflammatory response and the clinical signs of infection, and when tolerance to oral intake is adequate. Recommendation 11. In pregnant women with upper UTIs with no complications secondary to the primary infection, it is recommended to administer antibiotic therapy for a period of 7 to 10 days. Conclusions: It is expected that with this Colombian upper UTI consensus variability in clinical practice will be reduced. It is recommended that groups doing research in maternal fetal medicine assess the implementation and effectiveness of these recommendations.

Primary HPV-DNA screening in women under 30 years of age: health technology assessment / Tamización primaria con prueba ADN-VPH en mujeres menores de 30 años: evaluación de tecnología sanitaria

Background: Primary screening with Human Papilloma Virus (HPV) testing was introduced in Colombia in 2014 for individuals between 30 and 65 years of age. When the result is positive, cytology triage is performed for colposcopy referral. The convenience of initiating HPV-DNA testing for screening at 25 years of age is currently a subject of discussion. Therefore, the objective of this health technology assessment (HTA) is to analyze the available evidence regarding safety, efficacy, cost-effectiveness, values and preferences, ethical dilemmas and considerations pertaining to the implementation of the HPV-DNA test as a cervical screening strategy in women under 30 years of age in the Colombian context. Domains to be assessed: Clinical efficacy and safety 1. Cumulative rate of cervical intraepithelial neoplasia (CIN) grade 2 or high-er after 2 screening rounds. 2. Cumulative rates of invasive cancer of the uterine cervix after 2 screening rounds. 3. Safety: referral to colposcopy. Cost-effectiveness Cost-effectiveness for Colombia. Other domains considered Ethical considerations associated with cervical screening in women under 30 years of age. Organizational and individual considerations. Barriers and facilitators pertaining to the implementation of cervical screening in women under 30 years of age in the Colombian context. Methods: Clinical efficacy and safety assessment A systematic literature search of systematic reviews and clinical trials was conducted in MEDLINE, Embase and CENTRAL. The body of evidence was rated using the GRADE approach. An interdisciplinary team was then convened to create a working group to review the retrieved evidence. This led to the discussion and construction of the conclusions following the guidelines of a formal consensus in accordance with the RAND/UCLA methodology. Economic study Systematic literature research of studies that had assessed cost-effectiveness for Colombia. Results: Clinical outcomes An integrative analysis of 5 randomized clinical trials that met the inclusion critera was performed. Compared with cytology, primary HPV-DNA testing in women under 30 years of age could be associated with a lower frequency of CIN+2 lesions during the first screening round (RR: 1.57; CI: 1.20 to 2.04; low evidence certainty), and a lower incidence of CIN+2 (RR: 0.67; CI: 0.48 to 0.92; low evidence certainty). Moreover, it is associated with a lower frequency of invasive carcinoma at the end of follow-up (RR: 0.19; CI: 0.07 to 0.53; high evidence certainty). Economic results From the financial point of view, the use of HPVDNA testing plus cytology-based triage starting at 25 years of age is perhaps the most cost-effective option for Colombia (incremental cost-effectiveness ratio, COP 8,820,980 in 2013). Other implications Two studies suggest that barriers to implementation attributable to intermediation, public unrest and geographic considerations could be overcome with the use of new screening technologies or strategies. It is important to consider administration and service provision alternatives in order to overcome some acceptability and access barriers. Any cervical screening program must take into consideration ethical principles of nonmaleficence, beneficence, autonomy and equity. Future studies should focus on analyzing new screening techniques with emphasis on the population under 30 years of age. Conclusions: The use of HPV-DNA testing as a screening strategy in women under 30 years of age is a potentially efficacious and cost-effective intervention for Colombia. Future studies should focus on analyzing new screening technologies, with emphasis on the population under 30 years of age.

Antecedentes: A partir del 2014 en Colombia se incorporó la Tamización primaria con prueba de Virus del Papiloma Humano (VPH) desde los 30 hasta los 65 años, cuando la prueba es positiva se hace triage con citología para remisión a colposcopia. Actualmente se discute la conveniencia de iniciar la tamización con prueba de ADN de VPH a partir de los 25 años. De esta manera, el objetivo de esta evaluación de tecnologías sanitarias es analizar la evidencia disponible en torno a la seguridad, efectividad, costoefectividad, valores y preferencias, dilemas éticos y aspectos relacionados con la implementación para el contexto colombiano de la prueba ADN-VPH como estrategia de tamización cervical en mujeres menores de 30 años. Dominios a evaluar: Eficacia clínica y seguridad 1. Tasa acumulada de neoplasia intraepitelial cervical (NIC) grado 2 o más avanzado luego de 2 rondas de tamización. 2. Tasas acumuladas de cáncer invasor de cérvix luego de 2 rondas de tamización. 3. Seguridad: remisión a colposcopia. Costo-efectividad Costo efectividad para Colombia. Otros dominios considerados Aspectos éticos asociados a la tamización cervical en mujeres menores de 30 años. Aspectos organizacionales y del individuo. Barreras y facilitadores relacionados con la implementación en el contexto colombiano de la tamización cervical en mujeres menores de 30 años. Métodos: Evaluación de efectividad y seguridad clínicas Se realizó una búsqueda sistemática de la literatura en MEDLINE, Embase y CENTRAL de revisiones sistemáticas y ensayos clínicos. Se calificó el cuerpo de la evidencia con la aproximación GRADE. Posteriormente, se convocó a un grupo interdisciplinario a una mesa de trabajo en donde se presentó la evidencia recuperada, dando paso a la discusión y a la construcción de las conclusiones, siguiendo los lineamientos de un consenso formal acorde a la metodología RAND/UCLA. Estudio económico Se hizo una búsqueda sistemática de la literatura de estudios que hubieran evaluado el costo-efectividad para Colombia. Resultados: De 7.659 referencias recuperadas se incluyeron 8 estudios. Resultados clínicos Se realizó un análisis integrativo de 5 ensayos clínicos aleatorizados que cumplieron con los criterios de inclusión. Cuando se compara frente a la citología, la tamización primaria con ADN-VPH en mujeres menores de 30 años, podría asociarse con una mayor frecuencia de detección de lesiones NIC2+ durante la primera ronda de cribado (RR: 1.57; IC: 1,20 a 2,04; certeza en la evidencia baja), con una menor incidencia de NIC2+ (RR:0,67; IC: 0,48 a 0,92; certeza en la evidencia baja) y se asocia con una menor frecuencia de carcinoma invasor al término del seguimiento (RR: 0,19; IC: 0,07 a 0,53; certeza en la evidencia alta). Resultados económicos Desde el punto de vista económico, la alternativa de ADN-VPH y triage con citología desde los 25 años quizás representa la alternativa más costo-efectiva para Colombia (razón costo-efectividad incremental $8.820.980 COP año 2013). Otras implicaciones Dos estudios sugieren que las barreras de implementación, atribuibles a circunstancias de intermediación, de orden público y de carácter geográfico, podrían ser solventadas por nuevas tecnologías o estrategias de cribado. Es importante considerar alternativas de forma de administración y de prestación de servicios para solventar algunas barreras de aceptabilidad y acceso. Todo programa de tamización cervical debe contemplar los principios éticos de no maleficencia, beneficencia, autonomía y equidad. Futuros estudios deben enfocarse en analizar nuevas tecnologías de cribado con énfasis en población menor de 30 años. Conclusiones: El uso de la prueba ADN-VPH como estrategia de tamización en mujeres menores de 30 años es una intervención probablemente efectiva y costoefectiva para Colombia. Futuros estudios deben enfocarse en analizar nuevas tecnologías de cribado con énfasis en población menor de 30 años.

A systematic review of the prevalence of selected sexually transmitted infections in young people in Latin America.

Objective: To estimate the burden of Chlamydia trachomatis (CT), Neisseria gonorrhoeae (NG), Treponema pallidum (TP), and human papillomavirus (HPV) infections among people aged 10 to 25 in Latin America and the Caribbean. Methods: The MEDLINE, EMBASE, and LILACS databases were searched, as well as documents from regional organizations or national health Institutions. Population-based studies that reported prevalence or incidence of CT, NG, TP, and HPV detected through confirmatory tests in adolescents and young people were included. Two reviewers independently selected studies and extracted data. The quality of studies was assessed using the Newcastle-Ottawa Scale. Pooled estimators were calculated in cases where heterogeneity was <70%; when not feasible, prevalence ranges were reported. Results: Out of a total of 3 583 references, 15 prevalence studies complied with the inclusion criteria. Due to substantial heterogeneity (>70%), it was not possible to pool frequency estimators. Among the general population, the prevalence of CT infection ranged between 2.1% and 30.1% (9 studies, 5 670 participants); for NG, prevalence ranged between 0% and 2.9% (8 studies, 5 855 participants); for TP, prevalence varied between 0% and 0.7% (3 studies, 11 208 participants), and for HPV infection, prevalence ranged between 25.1% and 55.6% (8 studies, 3 831 participants). Conclusions: Reliable, population-based data on sexually transmitted infections (STIs) in adolescents and youth in Latin America and the Caribbean are limited. Additional studies are needed to better understand the burden of STIs in this population. However, given the substantial prevalence of STIs detected, countries need public health policies for prevention, early diagnosis, and treatment of STIs in young people.

A systematic review of the prevalence of selected sexually transmitted infections in young people in Latin America

[ABSTRACT]. Objective. To estimate the burden of Chlamydia trachomatis (CT), Neisseria gonorrhoeae (NG), Treponema pallidum (TP), and human papillomavirus (HPV) infections among people aged 10 to 25 in Latin America and the Caribbean. Methods. The MEDLINE, EMBASE, and LILACS databases were searched, as well as documents from regional organizations or national health Institutions. Population-based studies that reported prevalence or incidence of CT, NG, TP, and HPV detected through confirmatory tests in adolescents and young people were included. Two reviewers independently selected studies and extracted data. The quality of studies was assessed using the Newcastle–Ottawa Scale. Pooled estimators were calculated in cases where heterogeneity was <70%; when not feasible, prevalence ranges were reported. Results. Out of a total of 3 583 references, 15 prevalence studies complied with the inclusion criteria. Due to substantial heterogeneity (>70%), it was not possible to pool frequency estimators. Among the general population, the prevalence of CT infection ranged between 2.1% and 30.1% (9 studies, 5 670 participants); for NG, prevalence ranged between 0% and 2.9% (8 studies, 5 855 participants); for TP, prevalence varied between 0% and 0.7% (3 studies, 11 208 participants), and for HPV infection, prevalence ranged between 25.1% and 55.6% (8 studies, 3 831 participants). Conclusions. Reliable, population-based data on sexually transmitted infections (STIs) in adolescents and youth in Latin America and the Caribbean are limited. Additional studies are needed to better understand the burden of STIs in this population. However, given the substantial prevalence of STIs detected, countries need public health policies for prevention, early diagnosis, and treatment of STIs in young people.

[RESUMEN]. Objetivo. Calcular la carga de infecciones por Chlamydia trachomatis (CT), Neisseria gonorrhoeae (NG), Treponema pallidum (PT) y el virus del papiloma humano (VPH) en personas de edades comprendidas entre los 10 y los 25 años en América Latina y el Caribe. Métodos. Se realizaron búsquedas en las bases de datos MEDLINE, EMBASE y LILACS, así como en documentos de organizaciones regionales o instituciones nacionales de salud. Se incluyeron estudios poblacionales que notificaron la prevalencia o la incidencia de CT, NG, TP y VPH, detectados mediante pruebas confirmatorias en adolescentes y jóvenes. Dos revisores seleccionaron de forma independiente los estudios y extrajeron los datos. La calidad de los estudios se evaluó mediante la escala de Newcastle-Ottawa. Se hicieron estimaciones combinadas en los casos en que la heterogeneidad era <70 %; cuando no era posible, se presentaron los rangos de prevalencia. Resultados. De un total de 3 583 referencias, 15 estudios de prevalencia cumplieron los criterios de inclusión. Debido a una significativa heterogeneidad (>70%), no fue posible agrupar las estimaciones de frecuencia. En la población general, la prevalencia de infección por CT fluctuó entre 2,1 % y 30,1 % (9 estudios y 5 670 participantes); en el caso de NG, la prevalencia fluctuó entre 0 % y 2,9 % (8 estudios y 5 855 participantes); en el caso de PT, la prevalencia varió entre 0 % y 0,7 % (3 estudios y 11 208 participantes) y en el caso de infección por VPH, la prevalencia fluctuó entre 25,1 % y 55,6 % (8 estudios y 3 831 participantes). Conclusiones. Los datos poblacionales fiables sobre las infecciones de transmisión sexual (ITS) en adolescentes y jóvenes en América Latina y el Caribe son limitados. Es necesario hacer estudios adicionales para comprender mejor la carga de las ITS en este grupo poblacional. Sin embargo, dada la significativa prevalencia de ITS detectada, los países requieren políticas de salud pública para la prevención, el diagnóstico temprano y el tratamiento de las ITS en la población joven.

[RESUMO]. Objetivo. Estimar a carga de infecção por Chlamydia trachomatis (CT), Neisseria gonorrhoeae (NG), Treponema pallidum (TP) e papilomavírus humano (HPV) na população entre 10 e 25 anos de idade na América Latina e no Caribe. Métodos. Foi realizada uma pesquisa nas bases de dados MEDLINE, EMBASE e LILACS, assim como da documentação de entidades regionais ou nacionais que atuam na área da saúde. Foram incluídos na revisão estudos populacionais que registraram a incidência ou a prevalência de infecção por CT, NG, TP e HPV, verificada por meio de exames confirmatórios realizados em adolescentes e jovens. Dois revisores trabalharam de modo independente na seleção dos estudos e extração dos dados. A qualidade dos estudos foi avaliada utilizando a Escala de Newcastle-Ottawa. Foi feito o cálculo dos estimadores combinados quando a heterogeneidade era <70% e apresentada a variação da prevalência nos outros casos quando essa estimativa não foi possível. Resultados. Das 3 583 referências levantadas, 15 eram estudos de prevalência que satisfizeram os critérios de inclusão. Devido à heterogeneidade considerável entre os estudos (>70%), não foi possível combinar os estimadores de frequência. Na população geral, a prevalência de infecção por CT variou entre 2,1% e 30,1% (9 estudos, 5 670 participantes); a de NG, entre 0 e 2,9% (8 estudos, 5 855 participantes); a de TP, entre 0 e 0,7% (3 estudos, 11 208 participantes); e a de infecção por HPV, entre 25,1% e 55,6% (8 estudos, 3 831 participantes). Conclusões. Faltam dados populacionais confiáveis relativos a infecções sexualmente transmissíveis (ISTs) em adolescentes e jovens na América Latina e no Caribe. Outros estudos devem ser realizados para um entendimento melhor da carga dessas infecções na população. Diante da elevada prevalência verificada, os países precisam dispor de políticas de saúde pública para prevenção, diagnóstico precoce e tratamento de ISTs na população jovem.’

A systematic review of the prevalence of selected sexually transmitted infections in young people in Latin America / Revisión sistemática de la prevalencia de determinadas infecciones de transmisión sexual en la población joven en América Latina / Revisão sistemática da prevalência de determinadas infecções sexualmente transmissíveis em jovens na América Latina

ABSTRACT Objective. To estimate the burden of Chlamydia trachomatis (CT), Neisseria gonorrhoeae (NG), Treponema pallidum (TP), and human papillomavirus (HPV) infections among people aged 10 to 25 in Latin America and the Caribbean. Methods. The MEDLINE, EMBASE, and LILACS databases were searched, as well as documents from regional organizations or national health Institutions. Population-based studies that reported prevalence or incidence of CT, NG, TP, and HPV detected through confirmatory tests in adolescents and young people were included. Two reviewers independently selected studies and extracted data. The quality of studies was assessed using the Newcastle-Ottawa Scale. Pooled estimators were calculated in cases where heterogeneity was <70%; when not feasible, prevalence ranges were reported. Results. Out of a total of 3 583 references, 15 prevalence studies complied with the inclusion criteria. Due to substantial heterogeneity (>70%), it was not possible to pool frequency estimators. Among the general population, the prevalence of CT infection ranged between 2.1% and 30.1% (9 studies, 5 670 participants); for NG, prevalence ranged between 0% and 2.9% (8 studies, 5 855 participants); for TP, prevalence varied between 0% and 0.7% (3 studies, 11 208 participants), and for HPV infection, prevalence ranged between 25.1% and 55.6% (8 studies, 3 831 participants). Conclusions. Reliable, population-based data on sexually transmitted infections (STIs) in adolescents and youth in Latin America and the Caribbean are limited. Additional studies are needed to better understand the burden of STIs in this population. However, given the substantial prevalence of STIs detected, countries need public health policies for prevention, early diagnosis, and treatment of STIs in young people.

RESUMEN Objetivo. Calcular la carga de infecciones por Chlamydia trachomatis (CT), Neisseria gonorrhoeae (NG), Treponema pallidum (PT) y el virus del papiloma humano (VPH) en personas de edades comprendidas entre los 10 y los 25 años en América Latina y el Caribe. Métodos. Se realizaron búsquedas en las bases de datos MEDLINE, EMBASE y LILACS, así como en documentos de organizaciones regionales o instituciones nacionales de salud. Se incluyeron estudios poblacionales que notificaron la prevalencia o la incidencia de CT, NG, TP y VPH, detectados mediante pruebas confirmatorias en adolescentes y jóvenes. Dos revisores seleccionaron de forma independiente los estudios y extrajeron los datos. La calidad de los estudios se evaluó mediante la escala de Newcastle-Ottawa. Se hicieron estimaciones combinadas en los casos en que la heterogeneidad era <70 %; cuando no era posible, se presentaron los rangos de prevalencia. Resultados. De un total de 3 583 referencias, 15 estudios de prevalencia cumplieron los criterios de inclusión. Debido a una significativa heterogeneidad (>70%), no fue posible agrupar las estimaciones de frecuencia. En la población general, la prevalencia de infección por CT fluctuó entre 2,1 % y 30,1 % (9 estudios y 5 670 participantes); en el caso de NG, la prevalencia fluctuó entre 0 % y 2,9 % (8 estudios y 5 855 participantes); en el caso de PT, la prevalencia varió entre 0 % y 0,7 % (3 estudios y 11 208 participantes) y en el caso de infección por VPH, la prevalencia fluctuó entre 25,1 % y 55,6 % (8 estudios y 3 831 participantes). Conclusiones. Los datos poblacionales fiables sobre las infecciones de transmisión sexual (ITS) en adolescentes y jóvenes en América Latina y el Caribe son limitados. Es necesario hacer estudios adicionales para comprender mejor la carga de las ITS en este grupo poblacional. Sin embargo, dada la significativa prevalencia de ITS detectada, los países requieren políticas de salud pública para la prevención, el diagnóstico temprano y el tratamiento de las ITS en la población joven.

RESUMO Objetivo. Estimar a carga de infecção por Chlamydia trachomatis (CT), Neisseria gonorrhoeae (NG), Treponema pallidum (TP) e papilomavírus humano (HPV) na população entre 10 e 25 anos de idade na América Latina e no Caribe. Métodos. Foi realizada uma pesquisa nas bases de dados MEDLINE, EMBASE e LILACS, assim como da documentação de entidades regionais ou nacionais que atuam na área da saúde. Foram incluídos na revisão estudos populacionais que registraram a incidência ou a prevalência de infecção por CT, NG, TP e HPV, verificada por meio de exames confirmatórios realizados em adolescentes e jovens. Dois revisores trabalharam de modo independente na seleção dos estudos e extração dos dados. A qualidade dos estudos foi avaliada utilizando a Escala de Newcastle-Ottawa. Foi feito o cálculo dos estimadores combinados quando a heterogeneidade era <70% e apresentada a variação da prevalência nos outros casos quando essa estimativa não foi possível. Resultados. Das 3 583 referências levantadas, 15 eram estudos de prevalência que satisfizeram os critérios de inclusão. Devido à heterogeneidade considerável entre os estudos (>70%), não foi possível combinar os estimadores de frequência. Na população geral, a prevalência de infecção por CT variou entre 2,1% e 30,1% (9 estudos, 5 670 participantes); a de NG, entre 0 e 2,9% (8 estudos, 5 855 participantes); a de TP, entre 0 e 0,7% (3 estudos, 11 208 participantes); e a de infecção por HPV, entre 25,1% e 55,6% (8 estudos, 3 831 participantes). Conclusões. Faltam dados populacionais confiáveis relativos a infecções sexualmente transmissíveis (ISTs) em adolescentes e jovens na América Latina e no Caribe. Outros estudos devem ser realizados para um entendimento melhor da carga dessas infecções na população. Diante da elevada prevalência verificada, os países precisam dispor de políticas de saúde pública para prevenção, diagnóstico precoce e tratamento de ISTs na população jovem.'

Guía de práctica clínica basada en la evidencia para el manejo de trombocitopenia inmune primaria en población pediátrica / Evidence-based clinical practice guideline for the management of primary immune thrombocytopenia (ITP) in pediatric population

Primary immune thrombocytopenia (ITP) is the most common cause of thrombocytopenia in children, with a reported incidence of 1.1-12.5 cases per 100 000 children. However, currently, there are several definitions of ITP, as well as diagnostic and therapeutic approaches. To develop an evidence-based clinical practice guideline (CPG) to standardize the definition of ITP and, in this way, reduce the variability of its diagnosis, and to provide indications for the treatment of acute, persistent, and chronic ITP in patients under 18 years of age. The CPG was prepared by a multidisciplinary group that followed the Grading of Recommendations, Assessment, Development and Evaluations (GRADE) guidelines for developing CPGs, formulated PICO clinical questions, and conducted systematic reviews. GRADE evidence profiles were created and recommendations, with their corresponding level of evidence and strength, were made after a panel of experts assessed the benefit-risk balance, the quality of evidence, the patients' values and preferences, and the context in which they should be implemented. A total of 23 recommendations were made to pediatricians, hematologists, and health professionals working in emergency services for treating acute, persistent, and chronic ITP. Overall, the CPG has low quality of evidence, and the recommendations were made in order to improve the success rate of ITP treatment and the prognosis of children with this condition. Although ITP is the main cause of thrombocytopenia in pediatrics, to date there is not enough high-quality evidence that supports the recommendations presented here for its proper classification and treatment in children. Thus, further studies providing high-quality evidence on this issue are required.

La púrpura trombocitopénica inmunológica (PTI) es la causa más frecuente de trombocitopenia en población pediátrica, con una incidencia de 1.1 a 12.5 casos por cada 100 000 niños. Sin embargo, en la actualidad hay diferentes definiciones de PTI, así como enfoques diagnósticos y terapéuticos. Desarrollar una guía de práctica clínica (GPC) basada en la evidencia para unificar las definiciones de PTI, y de esta forma reducir la variabilidad de su diagnóstico, y para proporcionar indicaciones para el tratamiento de la PTI aguda, persistente y crónica en pacientes menores de 18 años. La GPC fue desarrollada por un grupo multidisciplinario, el cual siguió las guías GRADE para la realización de GPC, formuló preguntas clínicas PICO y realizó revisiones sistemáticas. Se crearon perfiles de evidencia GRADE y se realizaron las recomendaciones, con su respectivo nivel de evidencia y fortaleza, luego de que un panel de expertos evaluara el equilibrio beneficio-riesgo, la calidad de la evidencia, las preferencias y valoraciones de los pacientes y el contexto en el que debieran implementarse. Se formularon 23 recomendaciones para el tratamiento de la PTI aguda, persistente y crónica dirigidas a pediatras, hematólogos y profesionales de la salud que trabajan en servicios de urgencias. En general, la evidencia de la guía es de baja calidad y las recomendaciones fueron formuladas para mejorar la tasa de éxito del tratamiento de la PTI y el pronóstico de estos pacientes. A pesar de que la PTI es la principal causa de trombocitopenia en población pediátrica, actualmente no hay suficiente evidencia de alta calidad que respalde las recomendaciones aquí presentadas para su adecuada clasificación y tratamiento en niños. Por lo anterior, se requiere realizar nuevos estudios que brinden evidencia de alta calidad en el tema.

Evidence that the viral oncoproteins E6 and E7 of HPV induce the expression of a functional IL-2R on cervical cancer cells.

HPV-positive (HPV+) cervical cancer (CC) cells have been reported to express the IL-2 receptor (IL-2R) in contrast to virus-negative CC cells. This work was carried out to evaluate whether HPV infection induces IL-2R expression in CC cells. The analysis of the IL-2R expression data collected from The Cancer Genome Atlas (TCGA) and Genotype Tissue Expression project (GTEx) using the Xena platform demonstrate a higher expression of IL-2R subunits in CC tumors in comparison with normal tissues. Moreover IL-2Rß expression is consistently higher in HPV+ tumors versus HPV- tumors. Furthermore, it was demonstrated that transfection of the HPV E6/E7 genes into the C33A (HPV-) cell line promotes IL-2R expression and regulates proliferation in response to exogenous IL-2. Additionally, we found that HPV+ cell lines enhances their proliferation in co-culture with peripheral blood lymphocytes (PBLs). To corroborate that the viral proteins E6 and E7 were related to the effects mediated by IL-2, we used cells derived from the HeLa cell line in which the expression of E6/E7 has decreased, we found that it loses the ability to respond to the exogenous IL-2 stimuli. Finally, the importance of IL-2R in CC, as an immune escape mechanism, is discussed.

Evaluation of concordance among surgeons and pathologists regarding the diagnosis and classification of acute appendicitis in children.

Acute appendicitis is the most frequent urgent abdominal surgical pathology in children. Therapeutic decisions in patients who have undergone an appendectomy are made based on the macroscopic findings at the moment of surgery. There is high variability between surgical and histopathological findings. METHOD: Concordance among surgeons and pathologists regarding the diagnosis and classification of acute appendicitis was assessed in children who have undergone an appendectomy. Surgical site infection (SSI) incidence was measured for both the surgical and pathological classification. RESULTS: The statistical analysis included 1092 children. The pathologists confirmed the presence of appendicitis in 90.4% of the patients. Concordance in the diagnosis of appendicitis among surgeons and pathologists was weak (kappa 0.57), while concordance in the classification of perforated or non-perforated appendicitis was moderate (kappa 0.7). There were no significant differences in these findings determined by the surgeons' experience or the open or laparoscopic approach. In the discordant group of 70 patients in which the surgeon classified the appendicitis as non-perforated but the pathologist classified as perforated, just one patient developed an intra-abdominal abscess. CONCLUSIONS: The classification of appendicitis as perforated or non-perforated shows moderate concordance between the surgical and histopathological diagnosis. This concordance is not determined by the surgeons' experience or the surgical approach. TYPE OF STUDY: Diagnostic Test LEVEL OF EVIDENCE: Level II.

Propuesta biotecnológica para el tratamiento del cáncer de cérvix uterino, empleando liposomas / Biotechnological proposal for cervical cancer treatment using liposomes

Los nanotransportadores de fármacos son una excelente opción para formar sistemas farmacéuticos eficientes y seguros. Interleucina 2 (IL-2) es eficaz en la terapia antitumoral, sin embargo su administración sistémica se ha limitado por su alta toxicidad. En el presente trabajo se aborda la investigación en animales del tratamiento antitumoral con IL-2 transportada en liposomas frente a IL-2 libre, y se aborda un paso imprescindible para el futuro uso de los liposomas con IL-2 como terapia biotecnológica para pacientes con carcinoma de cérvix: los primeros estudios de estabilidad farmacéutica

Drug nanosystems are an excellent option to form efficient and safe pharmaceutical systems. Our team has developed methodology based on the use of Interleukin 2 (IL-2) which has proven very effective in antitumor therapy, but systemic administration is limited by its high toxicity. The present work discusses in vivo evaluation of the tumor using IL-2 carried in liposomes against IL-2 free, and also addresses an important and necessary step for the future use of IL-2 liposomes in biotechnology therapy for patients with carcinoma of the cervix: the early pharmaceutical stability studies

Brote de diarrea y transmisión de Cryptosporidium hominis asociados al uso de pañal en niños / Cryptosporidium hominis diarrhea outbreak and transmission linked to diaper infant use

Fundamento y objetivo: Ante la aparición de varios casos de criptosporidiosis en niños de una guardería, se estudió la extensión del brote y las causas de transmisión del parásito. Pacientes y método: Se diseñó un estudio de cohortes retrospectivo en el que se incluyó a todos los niños que asistían a la guardería en ese momento y a las cuidadoras, para determinar su estado de parasitación e identificar los factores de riesgo asociados al brote. Resultados: Durante el período de estudio se detectaron 24 casos de criptosporidiosis, 12 de ellos confirmados parasitológicamente, con una tasa de ataque de 0,46 (24/52). Ninguna de las cuidadoras presentó síntomas ni fue positiva al parásito. La transmisión de la infección presentó un patrón indicativo de mecanismos de persona a persona. Dentro de los factores de riesgo estudiados, los 2 únicos que pudieron relacionarse con la enfermedad fueron el uso de pañal (riesgo relativo = 2,06; p = 0,059) y la diarrea en familiares (riesgo relativo = 2,05; p = 0,01). La especie encontrada en los casos confirmados fue Cryptosporidium hominis (antes conocido como C. parvum, genotipo 1). Conclusiones: La criptosporidiosis debería contemplarse como posible causa de brotes de gastroenteritis en guarderías. Aumentar las precauciones higiénicas en las maniobras de cambio de pañal, especialmente en niños con diarrea, parece determinante para evitar la transmisión de Cryptosporidium

Background and objective: On the basis of several cases of cryptosporidiosis detected in a child day-care center, we stablished the extent of the outbreak and investigated causes of parasite transmission. Patients and method: A retrospective cohort study was designed on all children attending day-care center and care givers to determine their infection status and identify risk factors associated to the outbreak. Results: 24 cases of cryptosporidiosis were detected, with an attack rate of 0.46 (24/52); 12 of them were parasitologycally confirmed. All care givers were negative for Cryptosporidium and none of them reported symptoms of acute gastroenteritis. Transmission pattern was compatible with person to person modes. Among the factors investigated, two were associated with the risk of disease: diaper wear (relative risk = 2.06; p = 0.059); and diarrhea in relatives (relative risk = 2.05; p = 0.01). In all confirmed cases, Cryptosporidium hominis (previously known as C. parvum, genotype 1), was identified. Conclusions: Cryptosporidiosis should be considered as a possible cause of outbreaks of gastroenteritis at day-care centers. Increasing care on diaper changing practices, specially over children with diarrhea, may be the key factor to prevent transmission of Cryptosporidium