Clinical impact of Doppler reference charts on management of small-for-gestational-age fetuses: need for standardization.

OBJECTIVE: To assess clinical variability in the management of small-for-gestational-age (SGA) fetuses according to different published Doppler reference charts for umbilical artery (UA) and fetal middle cerebral artery (MCA) Doppler indices and cerebroplacental ratio (CPR). METHODS: We performed a systematic search of MEDLINE, EMBASE, CINAHL and the Web of Science databases from 1954 to 2018 for studies with the sole aim of creating fetal Doppler reference values for UA, MCA and CPR. The top cited articles for each Doppler parameter were included. Variability in Doppler values at the following clinically relevant cut-offs was assessed: UA-pulsatility index (PI) > 95th percentile; MCA-PI < 5th percentile; and CPR < 5th percentile. Variability was calculated for each week of gestation and expressed as the percentage difference between the highest and lowest Doppler value at the clinically relevant cut-offs. Simulation analysis was performed in a cohort of SGA fetuses (n = 617) to evaluate the impact of this variability on clinical management. RESULTS: From a total of 40 studies that met the inclusion criteria, 19 were analyzed (13 for UA-PI, 10 for MCA-PI and five for CPR). Wide discrepancies in reported Doppler reference values at clinically relevant cut-offs were found. MCA-PI showed the greatest variability, with differences of up to 51% in the 5th percentile value at term. Variability in the 95th percentile of UA-PI and the 5th percentile of CPR at each gestational week ranged from 21% to 41% and 15% to 33%, respectively. As expected, on simulation analysis, these differences in Doppler cut-off values were associated with significant variation in the clinical management of SGA fetuses, despite using the same protocol. CONCLUSIONS: The choice of Doppler reference chart can result in significant variation in the clinical management of SGA fetuses, which may lead to suboptimal outcomes and inaccurate research conclusions. Therefore, an attempt to standardize fetal Doppler reference ranges is needed. Copyright © 2019 ISUOG. Published by John Wiley & Sons Ltd.

Sepsis fulminante por Clostridium perfringens / Fulminant sepsis caused by Clostridium perfringens

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Differential effects of FXR or TGR5 activation in cholangiocarcinoma progression.

BACKGROUND AND AIMS: Cholangiocarcinoma (CCA) is an aggressive tumor type affecting cholangiocytes. CCAs frequently arise under certain cholestatic liver conditions. Intrahepatic accumulation of bile acids may facilitate cocarcinogenic effects by triggering an inflammatory response and cholangiocyte proliferation. Here, the role of bile acid receptors FXR and TGR5 in CCA progression was evaluated. METHODS: FXR and TGR5 expression was determined in human CCA tissues and cell lines. An orthotopic model of CCA was established in immunodeficient mice and tumor volume was monitored by magnetic resonance imaging under chronic administration of the specific FXR or TGR5 agonists, obeticholic acid (OCA) or INT-777 (0,03% in chow; Intercept Pharmaceuticals), respectively. Functional effects of FXR or TGR5 activation were evaluated on CCA cells in vitro. RESULTS: FXR was downregulated whereas TGR5 was upregulated in human CCA tissues compared to surrounding normal liver tissue. FXR expression correlated with tumor differentiation and TGR5 correlated with perineural invasion. TGR5 expression was higher in perihilar than in intrahepatic CCAs. In vitro, FXR was downregulated and TGR5 was upregulated in human CCA cells compared to normal human cholangiocytes. OCA halted CCA growth in vivo, whereas INT-777 showed no effect. In vitro, OCA inhibited CCA cell proliferation and migration which was associated with decreased mitochondrial energy metabolism. INT-777, by contrast, stimulated CCA cell proliferation and migration, linked to increased mitochondrial energy metabolism. CONCLUSION: Activation of FXR inhibits, whereas TGR5 activation may promote, CCA progression by regulating proliferation, migration and mitochondrial energy metabolism. Modulation of FXR or TGR5 activities may represent potential therapeutic strategies for CCA.

Impact of aspirin on trophoblastic invasion in women with abnormal uterine artery Doppler at 11-14 weeks: a randomized controlled study.

OBJECTIVE: Defective trophoblastic invasion is a key feature in many cases of pre-eclampsia (PE). Uterine artery (UtA) Doppler is a validated non-invasive proxy for trophoblastic invasion. The aim of this study was to explore whether low-dose aspirin, administered from the first trimester, improves trophoblastic invasion, evaluated by UtA Doppler during the second and third trimesters in women defined as high risk by abnormal first-trimester UtA Doppler. METHODS: This randomized Phase-II study had a triple-blind, parallel-arm, controlled design. Singleton pregnancies with abnormal mean UtA Doppler at 11-14 weeks and absence of other major risk factors for PE received 150 mg extended-release aspirin or identical-appearing placebo tablets from study inclusion to 28 weeks. Main outcome measure was UtA pulsatility index (PI) at 28 weeks' gestation. Secondary outcomes included frequency of development of PE and growth restriction/small-for-gestational age (SGA). RESULTS: A total of 155 women completed the follow-up and were analyzed. No difference in mean UtA-PI was found between women in the aspirin and placebo groups at 28 weeks (mean UtA-PI Z-score (mean ± SD), 0.99 ± 1.48 vs 0.85 ± 1.25; P = 0.52). Seven women developed PE: four (5%) in the aspirin group and three (4%) in the placebo group. There was a trend toward lower incidence of SGA in the aspirin group (8.8% vs 17.3%; P = 0.11). CONCLUSION: In women with defective trophoblastic invasion, as reflected by abnormal UtA Doppler, low-dose aspirin started in the first trimester does not have a significant effect on UtA impedance as pregnancy progresses; however, the study was underpowered to detect potential small effects . Copyright © 2016 ISUOG. Published by John Wiley & Sons Ltd.

Características clínicas de la epidemia de Dengue en el Servicio de urgencias del Hospital de clínicas / Clinical features of the Dengue epidemic in the emergency Department of the Hospital de clínicas

Introducción: El Dengue es una enfermedad infecciosa, sistémica y dinámica. Es una sola enfermedad, con diferentes presentaciones clínicas y evolución impredecible. Se hizo endémica en Paraguay desde el año 2002; el objetivo de este trabajo es determinar las características clínicas y epidemiológicas de la epidemia de diciembre de 2012 a febrero de 2013. Materiales y Métodos: Diseño descriptivo, retrospectivo, transversal. Fueron incluidos pacientes que desarrollaron criterios de casos probables de Dengue que consultaron al Servicio de Urgencias del Hospital de Clínicas. 1037 pacientes cumplían los criterios de inclusión. Resultados: La frecuencia de casos de Dengue fue del 14%. La edad promedio fue de 37,7 ± 16,3. El 56% era del sexo femenino. El 87% de los pacientes provenían del departamento Central. El mes de mayor número de casos con 48% fue febrero. El 83% de los pacientes fue tratado de forma ambulatoria. El promedio de días de internación fue de 2,39 ± 1,65. Sólo el 20% de los pacientes presentó algún tipo de comorbilidad. La fiebre estuvo presente en el 99,3% de los pacientes. El 20% de los pacientes tenía signos de alarma al momento de la consulta. La presión de pulso promedio fue 40,4 ± 12,1 La frecuencia cardiaca media fue de 93,8 ± 17,3. Promedio de hematocrito fue 42,2 ± 5,07. Promedio de plaquetas fue 111.500 ± 79972,1. Promedio de leucocitos 4561 ± 3717. Se registró un óbito. Conclusión: Este trabajo muestra las diferentes aristas de una de las epidemias más importantes desarrollada a nivel país. Palabras clave: dengue, características clínicas, hospital de clínicas

Background: Dengue is an infectious disease, systemic and dynamic. It presents several clinical manifestations and unpredictable outcome. It is endemic in Paraguay since year 2002; the aim of this research is to determine clinical and epidemiologic characters of the epidemic from December 2012 to February 2013. Methods: It was designed an cross sectional study, observational and retrospective. They were included patients that developed criteria of dengue cases that consulted in Emergencies Service of Clinics Hospital. Results: Frequency of Cases dengue were 14%. Age mean was 37, 7 ± 16,3. 56% were women. 87% of the patients came from Central Department. February was the month with mostly cases with 48%. 83% patients did not require internment. The average days of hospitalization were 2.39 ± 1.65. 20% of patient had some comorbidity. Fever was detected in 99,3% of patients. 20% had signs alarms at the moment of the consult. The average pulse pressure was 40,4 ± 12,1. The average cardiac frecuency was 93,8 ± 17,3. The average hematocrit was 42,2 ± 5,07. The average of platelets was 111.500 ± 79.972,1. The Average of leukocytes was 4561 ± 3717. One death was recorded. Conclusion: This paper shows the different aspects of one of the most important epidemics developed in our country. Keywords: dengue, clinical, hospital clinics.

Human toll-like receptor 1 T1805G polymorphism and susceptibility to pulmonary tuberculosis in northern Spain.

Toll-like receptors (TLRs) are key sensors of mycobacterial infections and play a crucial role in the initiation and coordination of the antimycobacterial innate immune response. T1805G, a functional TLR1 single nucleotide polymorphism (SNP), has been associated with susceptibility to pulmonary tuberculosis (PTB), but contradictory results among different populations have been reported. Our objective was to study this SNP in a genetically homogeneous population to evaluate its role in conferring susceptibility or resistance to PTB. In our population, the 1805G allele and the GG genotype (OR 2.04, 95%CI 1.26-3.31) influence susceptibility to PTB, in contrast with data observed in other populations.

[Detection of latent tuberculosis infection in peritoneal dialysis patients: new methods]. / Detección de la infección tuberculosa latente en pacientes en diálisis peritoneal: Nuevos métodos.

OBJECTIVE: The risk for tuberculosis (TB) is increased in patients with chronic renal failure and dialysis. Tuberculin skin test (TST) is the classical diagnostic method for screening despite its low sensitivity. New methods based on interferon-gamma have been developed. The aim of this study was to evaluate if Quantiferon® TB-gold In Tube (QFT-GIT) could be useful in the diagnosis of TB infection in patients on peritoneal dialysis (PD). PATIENTS AND METHODS: Fifty-four patients on PD were included in the study. They were evaluated for latent tuberculosis with QFT-GIT, TST and an assessment by an expert pulmonologist using patient's medical history and x-rays. Agreement between test results was determined. RESULTS: The prevalence of a positive TST was 29.6% for the first test and 31.5% for the second (booster effect). A positive chest x-ray increased the rate of detection of patients with latent TB infection up to 42.6% and the expert physician's evaluation to 44.4%. The correlation between QFT-GIT and TST was fair (k=0.36; P=.006), as it was between TST and expert physician's evaluation (k=0.257; P=.06). CONCLUSIONS: According to our experience QFT-GIT represents an important advantage in the diagnosis of latent TB infection in chronic renal failure patients on PD. It may complement but not replace TST.

Detección de la infección tuberculosa latente en pacientes en diálisis peritoneal: Nuevos métodos / Detection of latent tuberculosis infection in peritoneal dialysis patients: new methods

Introducción: El riesgo de tuberculosis (TB) está aumentado en pacientes con insuficiencia renal crónica y en diálisis. La prueba de la tuberculina (PT) es el test de cribado clásico en estos pacientes, a pesar de su baja sensibilidad. En los últimos años se han desarrollado nuevos métodos diagnósticos que se basan en la producción de interferón gamma tras la estimulación con antígenos de M. tuberculosis. El objetivo de este estudio fue evaluar si el Quantiferon® TB–gold In Tube (QFT–GIT) puede contribuir en el diagnóstico de la infección tuberculosa en pacientes en diálisis peritoneal (DP). Pacientes y métodos: Se incluyeron 54 pacientes en DP. Se valoró la posibilidad de infección tuberculosa latente mediante el QFT–GIT, la PT y la valoración clinicorradiológica por parte de un neumólogo experto. Se estudiaron las concordancias entre los tests. Resultados: La prevalencia de un resultado positivo para el test de la tuberculina fue del 29,6% para el primer test y del 31,5% para el segundo (valorando el efecto booster). Una radiografía de tórax positiva aumentaba la detección de infección tuberculosa latente hasta un 42,6% y la del neumólogo hasta un 44,4%. El nivel de correlación entre el QFT–GIT y la PT fue moderado (kappa = 0,36; p = 0,006), al igual que entre la PT y la valoración del neumólogo (kappa = 0,257, p = 0,06). Conclusiones: El QFT–GIT aporta algunas ventajas en el diagnóstico de la infección tuberculosa en pacientes con insuficiencia renal crónica en DP, y puede complementar a la prueba de la tuberculina (AU)

Objective: The risk for tuberculosis (TB) is increased in patients with chronic renal failure and dialysis. Tuberculin skin test (TST) is the classical diagnostic method for screening despite its low sensitivity. New methods based on interferon–gamma have been developed. The aim of this study was to evaluate if Quantiferon® TB–gold In Tube (QFT–GIT) could be useful in the diagnosis of TB infection in patients on peritoneal dialysis (PD). Patients and methods: Fifty–four patients on PD were included in the study. They were evaluated for latent tuberculosis with QFT–GIT, TST and an assessment by an expert pulmonologist using patient's medical history and x–rays. Agreement between test results was determined. Results: The prevalence of a positive TST was 29.6% for the first test and 31.5% for the second (booster effect). A positive chest x–ray increased the rate of detection of patients with latent TB infection up to 42.6% and the expert physician's evaluation to 44.4%. The correlation between QFT–GIT and TST was fair (ê=0.36; P=.006), as it was between TST and expert physician's evaluation (ê=0.257; P=.06). Conclusions: According to our experience QFT–GIT represents an important advantage in the diagnosis of latent TB infection in chronic renal failure patients on PD. It may complement but not replace TST (AU)

Alergia y salud mental. Estudio epidemiológico interdisciplinario / Allergy and mental health. Interdisciplinary epidemiological study

Fundamento. La asociación bidireccional entre factores psicosociales y afecciones alérgicas ha sido abordada históricamente con resultados poco concluyentes y el número de estudios que la abordan es escaso en Argentina. Objetivo. Valorar la asociación entre prevalencia de enfermedades alérgicas y variables del contexto de la salud mental. Lugar de aplicación. Facultad de Ciencias Médicas, Universidad Nacional de Rosario, Argentina. Diseño. Estudio observacional de corte transversal. Población. Se integró con 3.183 adultos jóvenes, 66,3% mujeres, entre 17 y 36 años. Método. Se utilizaron cuestionarios para enfermedades alérgicas y factores psicológicos y familiares. Resultados. Se observó ansiedad significativa en asociación con asma, rinitis, eccema, urticaria y angioedema. Se halló dificultad para identificar y distinguir sentimientos de sensaciones corporales y para describir sentimientos en los individuos sintomáticos. Se encontró mayor frecuencia de padres ausentes entre individuos que manifestaban asma o rinitis y de primogénitos en sujetos que referían rinitis. Todas las enfermedades se asociaron a la presencia de antecedentes familiares y al tabaquismo. Conclusión. La significativa asociación entre factores psicológicos y alergia agrega evidencias para sugerir la necesidad del abordaje interdisciplinario de alergia tanto en el campo de la investigación fisiopatológica o epidemiológica como en el terreno de la promoción, prevención y atención de la salud integral de las personas(AU)

Background. Bidirectional relationship between psychosocial factors and allergic processes has been historically assessed but remain inconclusive and not much explored in Argentine. Objective. To asses associations between allergic conditions prevalence and some factors related to mental health. Setting. Medical Sciences Faculty, National University of Rosario, Argentina. Design. Observational cross sectional study. Population. 3183 young adults, 66,3% female aged 17 to 36 years. Methods. Statement with different instruments for the symptomatic exploration of allergy and some psychological and familiar factors. Results. Significant anxiety in association with asthma, rhinitis, eczema, urticaria and angioedema were observed. Difficult to identify and distinguish feelings from corporal sensations and to describe feelings were observed in all allergic conditions. Individual which had shown asthma and rhinitis had more frequently the absence of father alive. Among rhinitis subjects the first order of birth was significantly observed. All diseases were associated with the presence of family history and smoking. Conclusion. Significant association between psychological factors and allergic condition were shown. Factors analyzed were related to genetic heritage as much as individual development in familiar and sociocultural environment. They constitute evidence enough to suggest the need of the interdisciplinary boarding of allergy so much at the field of the physiopathologic or epidemiologic investigation as in the ground of promotion, prevention and attention of the people comprehensive health.(AU)

[Proposal for a new microsurgical model for the study of induced endometriosis in Wistar rats. Preliminary results]. / Propuesta de un nuevo modelo microquirúrgico para el estudio de la endometriosis inducida en rata Wistar. Resultados preliminares.

The current knowledge status on the patogenesis of endometriosis as well as devastating consequences of disease evolution in women's reproductive health, have promoted researchers advances in a great manner during last years. The immunologic and neangiogenesis systems implication have opened new ways of knowledge over classic theories from the beginning of the xx century. The experimental resesearch, using animal induction models. Below we explain the first steps a new induction model ("PGR1-HotDog"), based on Wistar rats using a new disease autogeneration system, created for te study of the early stages of the endometriosis.

Propuesta de un nuevo modelo microquirúrgico para el estudiode la endometriosis inducida en rata Wistar. Resultados Preliminares / Proposal for a New Microsurgical Model for the Study of Induced Endometriosis in Wistar Rats. Preliminary Results

El desconocimiento actual sobre la patogenia de la endometriosis ylas devastadores consecuencias que conlleva esta enfermedad paralas mujeres en edad reproductiva, han sido las grandes promotorasde los esfuerzos de los investigadores en los últimos años. La implicaciónpatogénica del sistema inmunológico, así como de los procesosneoangiogénicos ha abierto una gran vía de conocimiento sobre lasteorías clásicas conocidas desde principios del siglo XX. Todo ello, pasapor la investigación experimental de la endometriosis, en modelosanimales, con sistemas de inducción de la enfermedad. A continuaciónexplicamos los primeros resultados de un nuevo modelo experimentalde autogeneración de endometriosis en rata Wistar (“PGR1-HotDog”),creado con una fi nalidad, el conocimiento de las fases más precocesde la enfermedad (AU)

The current knowledge status on the patogenesis of endometriosis aswell as devastating consequences of disease evolution in women´sreproductive health, have promoted researchers advances in a greatmanner during last years. The immunologic and neangiogenesis systemsimplication have opened new ways of knowledge over classic theoriesfrom the beginning of the XX century. The experimental resesearch,using animal induction models. Below we explain the fi rst steps a newinduction model (“PGR1-HotDog”), based on Wistar rats using a newdisease autogeneration system, created for te study of the early stagesof the endometriosis (AU)

Estado actual del diagnóstico del tromboembolismo pulmonar / Present state of the diagnosis of pulmonary thromboembolism

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Meckel's diverticulum adenocarcinoma: a rare malignant degeneration.

The case of a 40 year old male that, after the etiological study performed due to rectorrhages that was the only symptom he presented, was referred to an exploratory laparotomy. A disseminated adenocarcinoma arising in Meckels diverticulum was detected and palliative segmentary resection of the small bowel was performed. The lack of previous symptoms lead to the dissemination of the disease and to the impossibility of curative surgical resection of the tumor.

Inhibitory effect of short-term bile duct ligation on hepatic cytochrome P450 of bile acid-depleted rats.

In this study we analyzed the effect resulting from a short-term (1 h) bile duct obstruction in bile acid-depleted or taurocholate-replenished rats on liver cytochrome P450 enzyme system activity. Rats were depleted of endogenous bile acids and then subjected to a biliary obstruction for 1 h. Some of these depleted-obstructed rats were replenished previously to the obstruction with exogenous taurocholic acid (TC) and the others were treated with the solvent alone. To study the isolated effect of the bile acid, other rats were also previously depleted and then replenished with TC but they were obstructed briefly (20 min). CYP3A2-linked activity was evaluated in vivo with the aminopyrine breath test and in vitro by the measurement of nifedipine oxidase microsomal activity. The results suggested that bile flow suppression per se might inhibit this CYP-linked activity and that bile acid retention is not involved at least as a sole determinant.

[Effects of levofolinic acid on plasma homocysteine concentrations in healthy and young women in preconceptional care]. / Efecto del ácido levofolínico sobre las concentraciones de homocisteína plasmática en la mujer joven y sana en la consulta preconcepcional.

BACKGROUND: Increases in total plasmatic homocysteine (tHcy) represents a risk factor for neural tube defects. We studied the effects of levofolinic acid (l,5-formyl-tetrahydrofolic) on the plasmatic tHcylevels in women of child-bearing age. MATERIALS AND METHOD: Healthy women aged 18-35 years (n = 30) received levofolinic acid, 5 mg/day,orally for 30 days. Both tHcy and intraerythrocytic folate levels were measured before treatment (day 0), on days 2, 5, 10 and 30 within the treatment period and on days 30 (day 60) and 60 (day 90) after the treatment was finished. Plasmatic tHcy was measured by fluorescence polarisation immunoassay and intraerythrocyticfolates by chemiluminescent immunoassay. RESULTS: Plasmatic tHcy decreased from the second day of treatment onwards (day 0 vs. 2: mean of difference: -1.24 micromol/l; CI 95% = -0.84 to -1.63; p < 0.001). The maximum decline (32.3%) was observed after 30 days (mean of difference = -2.72 micromol/l; CI 95% = -2.20 to -3.24; p < 0.001).After finishing the treatment, the hypohomocysteinic effect persisted up to days 60 (mean of difference = -2.67 micromol/l; CI 95% = -2.07 to -3.26; p < 0.001)and 90 (mean of difference = -1.49 micromol/l; CI 95% = -0.94 to -2.03; p < 0.001). The response was greater when the plasmatic tHcy concentration was >= 9 micromol/l. CONCLUSIONS: Levofolinic acid leads to a earlier, intense and persistent drop of the plasmatictHcy levels.