Genotipificación del virus del papiloma humano en mujeres embarazadas VPH positivas / Genotyping of human papillomavirus in HPV-positive pregnant women

Resumen Antecedentes: Las embarazadas infectadas por el virus del papiloma humano presentan condiciones médicas que influyen en el curso de la enfermedad y pueden potenciar la posibilidad de transmisión vertical. Objetivo: Identificar los genotipos del virus del papiloma humano más frecuentes en mujeres embarazadas. Método: Estudio retrospectivo, observacional y descriptivo. Se emplearon muestras de raspado cervical. La extracción de material genético se hizo por la técnica de fenol-cloroformo y se amplificó empleando iniciadores universales MY09/MY11. Las muestras positivas se genotipificaron con un kit que detecta 37 genotipos diferentes. Resultados: Se identificaron 341 genotipos. Los más frecuentes fueron 16 (10.3%), 52 (8.8%) y 59 (8.6%). En el 75.9% la detección fue con un genotipo y en el 42.7% se detectaron infecciones múltiples. Conclusiones: Es sabido que la infección por virus del papiloma humano en mujeres embarazadas raramente evolucionará a lesiones invasivas. Se deberán considerar tanto las posibles complicaciones obstétricas a corto y largo plazo, así como las posibles repercusiones en la salud del recién nacido. La detección elevada del genotipo 16 sugiere un seguimiento estrecho para considerar un abordaje óptimo posterior a la gestación.

Abstract Background: Pregnant women infected with human papillomavirus have medical conditions that influence the course of the disease and can increase the possibility of vertical transmission. Objective: To identify the most common human papillomavirus genotypes in pregnant women. Method: Retrospective, observational and descriptive study. Cervical scraping samples were used. The extraction of genetic material was done by the phenol-chloroform technique and was amplified using universal primers MY09/MY11. Positive samples were genotyped with a kit that detects 37 different genotypes. Results: Three hundred forty-one genotypes were identified. The most frequent were 16 (10.3%), 52 (8.8%), and 59 (8.6%). In 75.9% the detection was with one genotype and in 42.7% multiple infections were detected. Conclusions: It is known that human papillomavirus infection in pregnant women will rarely evolve to invasive lesions. Both possible short- and long-term obstetric complications, as well as possible repercussions on the health of the newborn, should be considered. The high detection of genotype 16 suggests close follow-up to consider an optimal post-pregnancy approach.

Body mass index implications in intrahepatic cholestasis of pregnancy and placental histopathological alterations.

INTRODUCTION AND OBJECTIVES: Intrahepatic cholestasis is a frequent disease during pregnancy. It is unknown if liver function alterations produce specific placental lesions. The aim of this study was to evaluate placental histopathological changes in patients with intrahepatic cholestasis of pregnancy (ICP), and to explore correlations between the placental histopathology and hepatic function alteration or patient comorbidities, and body mass index. PATIENTS AND METHODS: A retrospective cohort study included women with ICP, most of them showing comorbidities such as overweight/obesity, preeclampsia and gestational diabetes. They were attended at the National Institute of Perinatology in Mexico City for three years. Placental histopathological alterations were evaluated according to the Amsterdam Placental Workshop Group Consensus Statement. Data was analyzed using Graph-Pad Prism 5. RESULTS: The results indicated that the placenta of ICP patients showed many histopathological alterations; however, no correlations were observed between the increase in bile acids or liver functional parameters and specific placental lesions. The most frequent comorbidities found in ICP patients were obesity, overweight and preeclampsia. Surprisingly, high percentage of ICP patients did not respond to UDCA treatment independently of the BMI group to which they belonged. CONCLUSION: The data suggest that ICP contribute to placental lesions. In addition, in patients with normal weight, an increase of chorangiosis and a reduced accelerated villous maturation without syncytial knots were observed in comparison with overweight and obese patients. It is necessary to improve the medical strategies in the treatment and liver disfunction surveillance of ICP patients.

Long-term recurrences and mortality in patients with noncardiac syncope.

INTRODUCTION AND OBJECTIVES: There are no in-depth studies of the long-term outcome of patients with syncope after exclusion of cardiac etiology. We therefore analyzed the long-term outcome of this population. METHODS: For 147 months, we included all patients with syncope referred to our syncope unit after exclusion of a cardiac cause. RESULTS: We included 589 consecutive patients. There were 313 (53.1%) women, and the median age was 52 [34-66] years. Of these, 405 (68.8%) were diagnosed with vasovagal syncope (VVS), 65 (11%) with orthostatic hypotension syncope (OHS), and 119 (20.2%) with syncope of unknown etiology (SUE). During a median follow-up of 52 [28-89] months, 220 (37.4%) had recurrences (21.7% ≥ 2 recurrences), and 39 died (6.6%). Syncope recurred in 41% of patients with VVS, 35.4% with OHS, and 25.2% with SUE (P=.006). In the Cox multivariate analysis, recurrence was correlated with age (P=.002), female sex (P <.0001), and the number of previous episodes (< 5 vs ≥ 5; P <.0001). Death occurred in 15 (3.5%) patients with VVS, 11 (16.9%) with OHS, and 13 (10.9%) with SUE (P=.001). In the multivariate analysis, death was associated with age (P=.0001), diabetes (P=.007), and diagnosis of OHS (P=.026) and SUE (P=.020). CONCLUSIONS: In patients with noncardiac syncope, the recurrence rate after 52 months of follow-up was 37.4% and mortality was 6.6% per year. Recurrence was higher in patients with a neuromedial profile and mortality was higher in patients with a nonneuromedial profile.

Desenlaces perinatales, en un centro de tercer nivel de México de pacientes con colestasis intrahepática del embarazo / Perinatal outcomes of patients with intrahepatic cholestasis of pregnancy in a third level center in Mexico

Resumen OBJETIVO: Describir la atención, tratamiento, desenlaces perinatales y complicaciones asociadas con la colestasis intrahepática del embarazo. MATERIALES Y MÉTODOS: Estudio de serie de casos, retrospectivo y observacional de pacientes embarazadas, con diagnóstico de colestasis intrahepática atendidas en el Instituto Nacional de Perinatología entre los meses de enero de 2016 a diciembre de 2020. Se evaluaron las características obstétricas, los datos demográficos, clínicos, bioquímicos y de tratamiento, la finalización del embarazo y los desenlaces perinatales. RESULTADOS: Se analizaron 67 casos de colestasis intrahepática que arrojaron una incidencia de 0.57%. La edad promedio de las pacientes fue 29.0 ± 6.8 años, 30 de 67 eran primigestas, 12 tuvieron el antecedente de colestasis intrahepática en el embarazo previo y 7 de óbito. El inicio de la enfermedad fue en el tercer trimestre en 41 de 67 pacientes. En los estudios de bioquímica 32 de 67 tuvieron valores de ácidos biliares entre 10 y 39 μM/L; 12 de las 67: 40-99 μM/L y 23 más de 100 (μM/L). Se administró tratamiento con ácido ursodesoxicólico a 63 de 67 y ante la falta de respuesta se agregó rifampicina. El promedio de semanas de gestación fue 35.6 ± 2.0 semanas con peso promedio de 2397 ± 572 g. Se encontró líquido amniótico con meconio en 10 neonatos y restricción del crecimiento en 20 de 67; se registraron 2 óbitos. CONCLUSIONES: Este es el primer estudio efectuado en México que describe la incidencia de la enfermedad y se utiliza la determinación de los ácidos biliares para establecer el diagnóstico. Los desenlaces perinatales coinciden con lo reportado en la bibliografía.

Abstract OBJECTIVE: To describe the care, treatment, perinatal outcomes and complications associated with intrahepatic cholestasis of pregnancy. MATERIALS AND METHODS: A retrospective and observational case series study of pregnant patients with a diagnosis of intrahepatic cholestasis seen at the National Institute of Perinatology between January 2016 and December 2020. Obstetric characteristics, demographic, clinical, biochemical and treatment data, pregnancy termination and perinatal outcomes were evaluated. RESULTS: Sixty-seven cases of intrahepatic cholestasis were analyzed, yielding an incidence of 0.57%. The mean age of the patients was 29.0 ± 6.8 years, 30 of 67 were primigravidases, 12 had a history of intrahepatic cholestasis in the previous pregnancy and 7 had an abortion. The onset of the disease was in the third trimester in 41 of 67 patients. In biochemistry studies 32 of 67 had bile acid values between 10 and 39 μM/L; 12 of 67: 40-99 μM/L and 23 more than 100 (μM/L). Treatment with ursodeoxycholic acid was administered to 63 of 67 and rifampicin to 4 patients. The mean number of weeks of gestation was 35.6 ± 2.0 weeks with a mean weight of 2397 ± 572 g. Amniotic fluid with meconium was found in 10 neonates and growth restriction in 20 of 67; there were 2 recorded abortions. CONCLUSIONS: This is the first study carried out in Mexico in which the incidence of the disease is described, and the determination of bile acids is used to establish the diagnosis. Perinatal outcomes coincide with those reported in the literature.

High Plasmatic Levels of Advanced Glycation End Products are Associated with Metabolic Alterations and Insulin Resistance in Preeclamptic Women.

AIMS: The purpose of this study was to investigate the association between plasmatic levels of advanced end glycation products (AGEs) and the metabolic profile in subjects diagnosed with preeclampsia, due to the known relation of these molecules with oxidative stress and inflammation, which in turn are related with PE pathogenesis. BACKGROUND: It has been reported that increased levels of AGEs are observed in patients with preeclampsia as compared with healthy pregnant subjects, which was mainly associated with oxidative stress and inflammation. Besides, in women with preeclampsia, there are metabolic changes such as hyperinsulinemia, glucose intolerance, dyslipidemia, among others, that are associated with an exacerbated insulin resistance. Additionally, some parameters indicate the alteration of hepatic function, such as increased levels of liver enzymes. However, the relationship of levels of AGEs with altered lipidic, hepatic, and glucose metabolism parameters in preeclampsia has not been evaluated. OBJECTIVE: To investigate the association between plasmatic levels of AGEs and hepatic, lipid, and metabolic profiles in women diagnosed with preeclampsia. METHODS: Plasma levels of AGEs were determined by a competitive enzyme-linked immunosorbent assay (ELISA) in 15 patients diagnosed with preeclampsia and 28 normoevolutive pregnant subjects (control group). Hepatic (serum creatinine, gammaglutamyl transpeptidase, aspartate transaminase, alanine transaminase, uric acid, and lactate dehydrogenase), lipid (apolipoprotein A, apolipoprotein B, total cholesterol, triglycerides, low-density lipoproteins, and high-density lipoproteins), and metabolic variables (glucose, insulin, and insulin resistance) were assessed. RESULTS: Plasmatic levels of AGEs were significantly higher in patients with preeclampsia as compared with the control. A positive correlation between circulating levels of AGEs and gamma-glutamyl transpeptidase, uric acid, glucose, insulin, and HOMA-IR levels was found in patients with preeclampsia. In conclusion, circulating levels of AGEs were higher in patients with preeclampsia than those observed in healthy pregnant subjects. Besides, variables of hepatic and metabolic profile, particularly those related to insulin resistance, were higher in preeclampsia as compared with healthy pregnant subjects. Interestingly, there is a positive correlation between AGEs levels and insulin resistance. CONCLUSIONS: Circulating levels of AGEs were higher in patients with preeclampsia than those observed in healthy pregnant subjects. Besides, hepatic and metabolic profiles, particularly those related to insulin resistance, were higher in preeclampsia as compared with healthy pregnant subjects. Interestingly, there is a positive correlation between AGEs levels and insulin resistance, suggesting that excessive glycation and an impaired metabolic profile contribute to the physiopathology of preeclampsia.

Liver disease in pregnancy: Medical aspects and their implications for mother and child.

Liver disease during pregnancy is more common than expected and may require specialized intervention. It is important to determine if changes in liver physiology may develop into liver disease, to assure early diagnosis. For adequate surveillance of mother-fetus health outcome, liver disease during pregnancy might require intervention from a hepatologist. Liver diseases have a prevalence of at least 3% of all pregnancies in developed countries, and they are classified into two main categories: related to pregnancy; and those non- related that are present de novo or are preexisting chronic liver diseases. In this review we describe and discuss the main characteristics of those liver diseases associated with pregnancy and only some frequent pre-existing and co-incidental in pregnancy are considered. In addition to the literature review, we compiled the data of liver disease occurring during pregnancies attended at the National Institute of Perinatology in Mexico City in a three-year period. In our tertiary referral women hospital, liver disease was present in 11.24 % of all pregnancies. Associated liver disease was found in 10.8% of all pregnancies, mainly those related to pre-eclampsia (9.9% of pregnancies). Only 0.56% was due to liver disease that was co-incidental or preexisting; the acute or chronic hepatitis C virus was the most frequent in this group (0.12%). When managing pregnancy in referral hospitals in Latin America, it is important to discard liver alterations early for adequate follow up of the disease and to prevent adverse consequences for the mother and child.

Genotipificación del virus del papiloma humano en mujeres que asisten a un hospital gineco-obstétrico de tercer nivel de la Ciudad de México / Genotyping of human papillomavirus in women attending a third-level of gynecological-obstetric hospital in Mexico City

Objetivo: Determinar la frecuencia de infección por el virus del papiloma humano en pacientes que acudieron a un hospital de tercer nivel de atención en la Ciudad de México. Método: Se realizó un estudio prospectivo, transversal y descriptivo que incluyó 65 mujeres entre 15 a 46 años que asistieron a consulta para atención gineco-obstétrica. A todas las participantes se les tomó una muestra cervical para la detección/genotipificación del papiloma virus mediante la prueba Linear Array HPV Genotyping Test in vitro® (Roche Molecular Systems, Inc., Branchburg, NJ). Resultados: Un total de 36 (55,4%) pacientes resultaron positivas al virus, en las que se identificaron 65 genotipos virales tanto en infección única (38,9%) como en infección por múltiples (61,1%) genotipos. El 29,2% de los genotipos identificados, fueron de alto riesgo. Los genotipos de alto riesgo más frecuentes fueron: VPH52 y 51; mientras que los genotipos de bajo riesgo más comunes fueron: VPH6 y 53. Un tercio de las pacientes con infección mostraron al menos un genotipo de alto riesgo. Conclusión: En este estudio, se observó una frecuencia relativamente baja de genotipos de alto riesgo del virus del papiloma humano, sin embargo se identificó un porcentaje importante de co-infección por múltiples genotipos. Por esta razón, se considera necesario dar seguimiento a mediano y largo plazo para monitorear la evolución de la infección.

Objective: To identify which are the most frequent genotypes of human papilloma virus among a group of gynecologic-obstetric patients at tertiary care hospital in Mexico City. Method: A prospective and descriptive cross-sectional study was carried out among a group of 65 women, aged 15-46 years, receiving gynecological-obstetric care. Cervical specimens were taken from all participants for direct HPV detection/ genotyping by means of a Linear Array HPV Genotyping Test in vitro® (Roche Molecular Systems, Inc., Branchburg, NJ). Results: Virus detection was achieved in 36 patients (55.4%), with a total of 65 genotypes, either as single (38.9%) or multiple-genotype (61.1%) infections. High risk genotypes accounted for only 29.2% of all genotype. The most frequent high risk genotypes were HPV52 and 51, while HPV6 and 53 were the most frequent low risk ones. At least one high risk genotype was present in one third of infected patients. Conclusion: The relative low frequency of oncogenic human papilloma virus genotypes among the women in this study was observed, however a significant percentage of co-infection with multiple genotypes were identified. Thus, mid- to long-term follow up might be necessary for those patients to monitor the evolution of the infection.

Molecular subtypification of human papillomavirus in male adult individuals with recurrent respiratory papillomatosis.

OBJECTIVE: This study aimed to identify the isotype of human papillomavirus (HPV) in fresh tissue samples of 35 male adults with adult recurrent adult respiratory papillomatosis which may be important to define the precise etiology of the disease, and determine the therapeutic and prophylactic measures. METHODS: A total of 35 adult male patients diagnosed with active RRP who have been treated for several years were included in the study. DNA of patients was extracted from fresh biological samples and analyzed by PCR and a Linear Array® HPV Genotyping system. RESULTS: Most cases (95%) corresponded to adult-onset of RRP. A questionnaire was applied to obtain demographic and clinical data. Using a PCR-based detection system all patients showed the presence of HPV; 80% were positive for HPV-6, 8% for HPV-11 and one for HPV-16. CONCLUSION: Most patients presented HPV-6 and consequently it was not feasible to correlate clinical and demographic characteristics with viral type. Besides, co-infections were not evident. This knowledge may be relevant to delineate therapeutic and preventive measures.