Diagnóstico prenatal de malformaciones congénitas y alteraciones cromosómicas: resultado de la experiencia CIMAF - Hospital Dr. Sótero Del Río / Prenatal Diagnosis of Congenital Malformations and Chromosomal Abnormalities: Single Center Experience - Hospital Dr. Sótero Del Río, Chile

INTRODUCCIÓN: El diagnóstico prenatal de anomalías congénitas tiene como objetivo ofrecer consejería apropiada, identificar aquellas patologías que se benefician de terapia fetal y coordinar la derivación de estas pacientes a centros terciarios para un óptimo manejo perinatal. Para el diagnóstico y manejo de las anomalías congénitas en el Hospital Dr. Sótero Del Río contamos con un equipo multidisciplinario. El objetivo de este estudio es describir nuestra experiencia como centro de referencia en Santiago de Chile en relación al diagnostico prenatal de malformaciones congénitas, estudio genético prenatal y resultados perinatales. MÉTODOS: Estudio retrospectivo y descriptivo. Se incluyó a las pacientes registradas en las bases de datos ecográficas entre 2010 y 2019 del Hospital Dr. Sotero del Rio. Se revisaron fichas clínicas para evaluación y seguimiento postnatal. RESULTADOS: Se evaluaron 404 pacientes con sospecha de malformaciones congénitas o marcadores de aneuploidías. La edad gestacional media de la evaluación fue 29 semanas (14-38 semanas). La mediana de la edad gestacional al parto fue 37.6 semanas (20-41 semanas). Se obtuvo un 78% de recién nacidos vivos, 12% óbitos fetales y 10% mortineonatos. Las malformaciones más frecuentes fueron cardiovasculares, sistema nervioso central, hidrops, extremidades, abdomen y genitourinario. Se realizo el estudio genético en 232 pacientes; 61% resultado normal, 12.5% trisomía 21, 8% trisomía 18, 4% trisomía 13, 4% XO, 4% otras. Se analizaron las pacientes que se acogieron a la ley de interrupción voluntaria del embarazo. CONCLUSIÓN: Destacamos la importancia de derivación a centros de referencia de pacientes con sospecha de malformaciones congénitas para un adecuado diagnostico prenatal, ofrecer un manejo con equipo multidisciplinario y así mejorar los resultados neonatales.

INTRODUCTION: The objectives of prenatal diagnosis of fetal malformations are to offer the patient and her family the proper counseling, identify those conditions that benefits of prenatal therapy and to coordinate the referral to tertiary centers to improve neonatal survival. Our hospital counts with a multidisciplinary team who evaluate the patients together. The objective of this study is to describe our experience as a referral center in prenatal diagnosis, management and neonatal outcomes in Santiago de Chile. METHODS: Retrospective and descriptive study. Patients registered in our prenatal diagnosis database between September 2010 and July 2019 were included. Clinical files were reviewed for neonatal outcomes. OUTCOMES: 404 patients with congenital malformations or aneuploidy markers were evaluated. The average gestational age of the evaluation was 29 weeks. Median gestational age to delivery was 37 weeks plus 6 days. 78% of livebirth, 12% fetal demise and 10% of neonatal death were obtained. The most frequent fetal malformations were cardiovascular, central nervous system, fetal hydrops, extremities, abdominal wall defects and urinary system. Fetal karyotype was performed in 232 patients; 61% normal karyotype, 12.5% trisomy 21, 8% trisomy 18, 4% trisomy 13, 4% monosomy X, 4% others. We also analyze the patients who agreed to termination of pregnancy according to Chilean legislation. CONCLUSION: We highlight the importance of referral of patients with suspected fetal malformations to tertiary centers for an adequate evaluation by a multidisciplinary team of specialists, to improve the survival and neonatal outcome.

Comparison of two identification and susceptibility test kits for Ureaplasma spp and Mycoplasma hominis in amniotic fluid of patients at high risk for intra-amniotic infection.

Objective: Ureaplasma urealyticum and Mycoplasma hominis are the most common microorganisms found in the amniotic fluid of patients at risk for preterm delivery. However, culture techniques for genital mycoplasms require special conditions, are barely considered as part of the evaluation of suspected intra-amniotic infection (IAI) and the results are available within 2 and 7 days. The objectives of this study are to validate the use of two commercially available kits (Mycoplasma IES y MYCOFAST® RevolutioN) for the identification of Ureaplasma spp. and Mycoplasma hominis in amniotic fluid, to compare the results of these kits with those obtained by culture and real-time polymerase chain reaction (qPCR) and to report the antibiotic sensitivity profile of the genital mycoplasms identified.Methods: This is a prospective cohort study including women with singleton and twin gestations between 16 and 36 weeks. Patients were admitted to perform an amniocentesis due to pregnancy complications considered at high risk for IAI (e.g. preterm labor with intact membranes, preterm prelabour rupture of membranes, short cervix, etc.), treatment of polyhydramnios, and for the assessment of fetal death and fever without a focus.Results: Overall, 93 patients underwent amniocentesis and 63 had results available for all tests. The prevalence of a positive culture was 6% (4/63). There were four cases of Ureaplasma spp. and none of Mycoplasma hominis. The qPCR identified one case as Ureaplasma spp., one case as Ureaplasma parvum and two cases as Ureaplasma urealyticum. For all tests, the diagnostic performance was as follows: sensitivity 100% [95% CI (39.8-100%)], specificity 100% [95% CI (93.9-100%)], positive predictive value 100% [95% CI (39.8-100%)] and negative predictive value 100% [95% CI (93.9-100%)]. In this cohort, Ureaplasma spp. showed low resistance to erythromycin, but a high resistance to clindamycin and clarithromycin that may change according to the antibiotic concentration.Conclusions: To our knowledge, this is the first study that validates the use of the Mycoplasma IES and MYCOFAST® RevolutioN kits for the identification of genital mycoplasmas in amniotic fluid. The results of these kits are mostly available within 24 hours, have an excellent correlation with those from broth cultures and qPCR and characterize the antibiotic sensitivity profile of the genital mycoplasms identified, providing an opportunity for specific treatment in cases of IAI. Further validation studies in other populations are needed.

Computational de-orphanization of the olive oil biophenol oleacein: Discovery of new metabolic and epigenetic targets.

The health promoting effects of extra virgin olive oil (EVOO) relate to its unique repertoire of phenolic compounds. Here, we used a chemoinformatics approach to computationally identify endogenous ligands and assign putative biomolecular targets to oleacein, one of the most abundant secoiridoids in EVOO. Using a structure-based virtual profiling software tool and reference databases containing more than 9000 binding sites protein cavities, we identified 996 putative oleacein targets involving more than 700 proteins. We subsequently identified the high-level functions of oleacein in terms of biomolecular interactions, signaling pathways, and protein-protein interaction (PPI) networks. Delineation of the oleacein target landscape revealed that the most significant modules affected by oleacein were associated with metabolic processes (e.g., glucose and lipid metabolism) and chromatin-modifying enzymatic activities (i.e., histone post-translational modifications). We experimentally confirmed that, in a low-micromolar physiological range (<20 µmol/l), oleacein was capable of inhibiting the catalytic activities of predicted metabolic and epigenetic targets including nicotinamide N-methyltransferase, ATP-citrate lyase, lysine-specific demethylase 6A, and N-methyltransferase 4. Our computational de-orphanization of oleacein provides new mechanisms through which EVOO biophenols might operate as chemical prototypes capable of modulating the biologic machinery of healthy aging.

Patients with acute cervical insufficiency without intra-amniotic infection/inflammation treated with cerclage have a good prognosis.

Background The frequency of intra-amniotic infection/inflammation (IAI/I) in patients with midtrimester cervical insufficiency is up to 50%. Our purpose was to determine the perinatal outcomes of cervical cerclage in patients with acute cervical insufficiency with bulging membranes, and to compare the admission-to-delivery interval and pregnancy outcomes according to the results of amniotic fluid (AF) analysis and cerclage placement. Methods This was a retrospective cohort study including singleton pregnancies with cervical insufficiency between 15 and 26.9 weeks in two tertiary health centers. IAI/I was defined when at least one of the following criteria was present in AF: (a) a white blood cell (WBC) count >50 cells/mm3; (b) glucose concentration <14 mg/dL; and/or (c) a Gram stain positive for bacteria. Three different groups were compared: (1) absence of IAI/I with placement of a cerclage; (2) amniocentesis not performed with placement of a cerclage; and (3) IAI/I with or without a cerclage. Results Seventy patients underwent an amniocentesis to rule out IAI/I. The prevalence of IAI/I was 19%. Forty-seven patients underwent a cerclage. Patients with a cerclage had a longer median admission-to-delivery interval (33 vs. 2 days; P < 0.001) and delivered at a higher median gestational age (27.4 vs. 22.6 weeks; P = 0.001) than those without a cerclage. The neonatal survival rate in the cerclage group was 62% vs. 23% in those without a cerclage (P = 0.01). Patients without IAI/I who underwent a cerclage had a longer median admission-to-delivery interval (43 vs. 1 day; P < 0.001), delivered at a higher median gestational age (28 vs. 22.1 weeks; P = 0.001) and had a higher neonatal survival rate (67% vs. 8%; P < 0.001) than those with IAI/I. Conclusion The pregnancy outcomes of patients with midtrimester cervical insufficiency and bulging membranes are poor as they have a high prevalence of IAI/I. Therefore, a pre-operative amniocentesis is key to identify the best candidates for the subsequent placement of a cerclage.

Transabdominal collection of amniotic fluid "sludge" and identification of Candida albicans intra-amniotic infection.

A G3P2 patient who conceived while using an intrauterine contraceptive device (IUD) presented at 20 weeks of gestation with mild irregular uterine contractions and vaginal bleeding. Sonographic examination at admission showed the presence of dense amniotic fluid "sludge" and a long sonographic uterine cervix (42 mm). To assess the microbiologic significance of amniotic fluid "sludge", we performed a transabdominal amniocentesis. The procedure was performed under real-time ultrasound, and fluid resembling pus at gross examination was noted. Rapid amniotic fluid analysis showed the presence of a high white blood cell count and structures resembling hyphae. Amniotic fluid cultures were positive for Candida albicans. Treatment was begun with broad-spectrum antibiotics, including Fluconazole, upon the visualization of pus in the "sludge" material because of the presence of hyphae in the Gram stain. Despite treatment, the patient went into spontaneous preterm labor and delivered five days after admission. Placental examination revealed acute fungal histologic chorioamnionitis and funisitis. This represents the first report of transabdominal collection and analysis of amniotic fluid "sludge" and the microbiologic detection of Candida albicans in this material. This report provides evidence that transabdominal retrieval of "sludge" is possible and may be of significant value for patient management and selection of antimicrobial agents.

Morbimortalidad perinatal en pacientes con rotura prematura ovular ≤24 semanas según cantidad de líquido amniótico al momento del diagnóstico / Perinatal morbidity and mortality in patients with premature ovular rupture ≤24 weeks according to amount of amniotic fluid at diagnosis

Introducción: La rotura prematura ovular (RPO) antes de la viabilidad fetal consiste en una complicación obstétrica de baja incidencia, pero de alta morbimortalidad perinatal asociada. Estudios sugieren que el volumen de líquido amniótico (LA) es un factor importante a considerar. El objetivo de este trabajo es evaluar si en RPO ≤24 semanas, un bolsillo vertical máximo (BVM) <2cm al diagnóstico es un factor de riesgo para aparición de morbimortalidad fetal y neonatal. Métodos: Estudio de cohorte longitudinal retrospectivo de 94 pacientes con RPO ≤24 semanas ingresadas a un hospital terciario para manejo expectante entre los años 2005 y 2014. Embarazo gemelar o malformaciones congénitas fueron criterios de exclusión. Se obtuvieron y compararon 2 grupos según BVM al ingreso (BVM ≥ 2 cm y BVM < a 2 cms) y se comparó la edad gestacional (EG) al momento de la RPO y al parto, la latencia desde la RPO al parto, la presencia de corioamnionitis clínica, el número de óbitos fetales, muerte neonatal precoz (primeros 7 días de vida), tardía (entre los 7 y 28 días) y sobrevida global. Resultados: El 58 por ciento de las pacientes presentó un BVM <2 cm al ingreso, el cual se asoció a menor latencia al parto (p:0,01), menor EG al parto (p:0,02), más óbito fetal (p:0,04), mayor muerte neonatal precoz y tardía (p:0,02 y 0,01 respectivamente) además de menor sobrevida global (p:0,01). Conclusiones: La medición de BVM <2 cm al ingreso en pacientes con RPO ≤24 semanas, es un factor de mal pronóstico y debe ser considerado en el manejo clínico de estas pacientes.(AU)

Introduction: Previable premature rupture of membranes (pPROM) is a low-incidence obstetric complication associated with high perinatal morbidity and mortality. Studies suggest that the volume of amniotic fluid (AL) is an important factor to consider. The aim of this study is to evaluate if in RPO ≤24 weeks, a maximum vertical pocket (MVP) <2 cm to the diagnostic is a risk factor for fetal and neonatal morbidity and mortality. Objectives: Evaluate fetal and neonatal morbidity and mortality according to amniotic fluid (AL) Maximum Vertical Pocket (MVP) ≥ or

Resultado de estudio prenatal invasivo para el diagnóstico de aneuploidía en el Hospital Sótero del Río / Results of an invasive prenatal study for the diagnosis of aneuploidy at Hospital Sótero del Río

ANTECEDENTES: Las aneuploidías y malformaciones congénitas son causa importante de morbi-mortalidad perinatal e infantil en Chile. OBJETIVO: Evaluar la realidad local del diagnóstico genético antenatal para mejorar el resultado perinatal. MÉTODOS: Estudio retrospectivo y descriptivo. Se realizó amniocentesis a embarazadas con indicación de estudio genético prenatal por sospecha ecográfica de alteraciones cromo-sómicas, entre octubre de 2010 y marzo de 2015, en el Hospital Sótero del Río. RESULTADOS: Los hallazgos ecográficos más frecuentes fueron: cardiopatías congénitas, malformaciones del sistema nervioso central y restricción de crecimiento fetal precoz. 164 pacientes aceptaron el estudio invasivo antenatal, obteniéndose resultados de 154. El promedio de edad materna y edad gestacional del examen fueron 30 años y 27+3 semanas, respectivamente. En embarazos con trisomía 21 y 13, el 71% de las pacientes tenía sobre 35 años. Un 31% de las muestras presentaron cariotipo anormal, siendo la más frecuente la trisomía 21 (14%), trisomía 18 (9%), monosomía X (4,5%) y trisomía 13 (2,6%). CONCLUSIÓN: El diagnóstico genético prenatal permite un adecuado manejo perinatal, coordinación apropiada entre las unidades de Obstetricia y Neonatología, y la preparación de las pacientes y sus familias para un pronóstico perinatal adverso.

BACKGROUND: Malformations and aneuploidy are a major cause of perinatal morbidity and mortality in Chile. Invasive techniques are offered to determine the fetal karyotype, when there is an abnormal finding in the ultrasound. AIMS: To assess the local situation of prenatal genetic diagnosis to improve the management of this population. METHODS: This is a retrospective and descriptive study of patients from october 2010 to march 2015, who had an amniocentesis for genetic testing due suspected fetal malformations or aneu-ploidy. RESULTS: The sonographic findings most frequently found were: congenital heart disease, malformations of the central nervous system and early growth restrictions. 164 patients agree to perform invasive prenatal genetic, obtaining 154 results. The average maternal age was 30 years and the mean gestational age at amniocentesis was 27+3 weeks. In trisomy 21 pregnancies, 71% of patients were higher than 35 years. 31% of the samples had abnormal karyotype: trisomy 21 (14%), trisomy 18 (9%), Turner's syndrome (4.5%) and trisomy 13 (3%). CONCLUSIONS: Prenatal genetic diagnosis allows appropriate perinatal management and contributes to prepare the patient and their families for an adverse perinatal outcome.

Adrenalectomy prevents renal ischemia-reperfusion injury.

Spironolactone treatment prevents renal damage induced by ischemia-reperfusion (I/R), suggesting that renoprotection conferred by spironolactone is mediated by mineralocorticoid receptor (MR) blockade. It is possible, however, that this effect is due to other mechanisms. Therefore, this study evaluated whether adrenalectomy prevented renal damage induced by I/R. Three groups of Wistar rats were studied: 1) a group subjected to a sham surgery, 2) a group subjected to bilateral I/R, and 3) a group of rats in which adrenal glands were removed 3 days before induction of I/R. As expected, I/R resulted in renal dysfunction and severe tubular injury that was associated with a significant increase in tubular damage markers. In contrast, there was no renal dysfunction or tubular injury in rats that were adrenalectomized before I/R. These effects were demonstrated by normalization of glomerular filtration rate, markers of oxidative stress, and tubular injury markers in adrenalectomized rats. The renoprotection observed was associated with the reestablishment of nitric oxide metabolites, increased endothelial nitric oxide synthase expression and its activating phosphorylation, as well as normalization of Rho-kinase expression and ET(A) mRNA levels. Our results show that aldosterone plays a central role in the pathogenesis of renal damage induced by I/R and that MR blockade may be a promising strategy that opens a new therapeutic option for preventing acute renal injury.

Reversal of diabetes by pancreatic islet transplantation into a subcutaneous, neovascularized device.

BACKGROUND: Transplantation of pancreatic islets for the treatment of type 1 diabetes allows for physiologic glycemic control and insulin-independence when sufficient islets are implanted via the portal vein into the liver. Intrahepatic islet implantation requires specific infrastructure and expertise, and risks inherent to the procedure include bleeding, thrombosis, and elevation of portal pressure. Additionally, the relatively higher drug metabolite concentrations in the liver may contribute to the delayed loss of graft function of recent clinical trials. Identification of alternative implantation sites using biocompatible devices may be of assistance improving graft outcome. A desirable bioartificial pancreas should be easy to implant, biopsy, and retrieve, while allowing for sustained graft function. The subcutaneous (SC) site may require a minimally invasive procedure performed under local anesthesia, but its use has been hampered so far by lack of early vascularization, induction of local inflammation, and mechanical stress on the graft. METHODS: Chemically diabetic rats received syngeneic islets into the liver or SC into a novel biocompatible device consisting of a cylindrical stainless-steel mesh. The device was implanted 40 days prior to islet transplantation to allow embedding by connective tissue and neovascularization. Reversal of diabetes and glycemic control was monitored after islet transplantation. RESULTS: Syngeneic islets transplanted into a SC, neovascularized device restored euglycemia and sustained function long-term. Removal of graft-bearing devices resulted in hyperglycemia. Explanted grafts showed preserved islets and intense vascular networks. CONCLUSIONS: Ease of implantation, biocompatibility, and ability to maintain long-term graft function support the potential of our implantable device for cellular-based reparative therapies.

Vólvulo de Sigmoides:experiencia internacionalista en 58 casos / Sigmoid volvulus:internationalist experience in 58 cases

Se estudiaron 10 pacientes con diagnóstico de vólvulo de sigmoides en Etiopía por diferentes métodos. Esta afección se presenta como la primera causa de obstrucción intestinal en dicho país, y representa el 60,1 por ciento de la serie estudiada. La forma de presentación subaguda fue la más frecuente, para alcanzar el 74 por ciento y se valora la aparición de esta enfermedad en pacientes jóvenes como un hecho relevante. La sutura primaria se utilizó en este medio con buenos resultados al no reportar dehiscencias de sutura. La gravedad con que se presentan estos enfermos, en ocasiones con necrosis intestinal, hace que la mortalidad sea elevada

Vólvulo de Sigmoides.experiencia internacionalista en 58 casos / Sigmoid volvulus:internationalist experience in 58 cases

Se estudiaron 10 pacientes con diagnóstico de vólvulo de sigmoides en Etiopía por diferentes métodos. Esta afección se presenta como la primera causa de obstrucción intestinal en dicho país, y representa el 60,1 por ciento de la serie estudiada. La forma de presentación subaguda fue la más frecuente, para alcanzar el 74 por ciento y se valora la aparición de esta enfermedad en pacientes jóvenes como un hecho relevante. La sutura primaria se utilizó en este medio con buenos resultados al no reportar dehiscencias de sutura. La gravedad con que se presentan estos enfermos, en ocasiones con necrosis intestinal, hace que la mortalidad sea elevada

Esplenectomía parcial: informe de 3 pacientes operados / Partial splenectomy: report of three surgical patients

Se revisaron 3 historias clínicas de pacientes afectados de quistes esplénicos a los cuales se les realizó esplenectomía parcial como método reciente de la cirugía conservadora del bazo. Las intervenciones se efectuaron en el Hospital Provincial Docente Clinicoquirúrgico de Villa Clara en un período de 2 años (1986-1987). Se detalla la técnica quirúrgica empleada y se informa que no se presentó ninguna complicación, principalmente la hemorragia. En esta cirugía no se reporta mortalidad

Esplenectomía parcial. informe de 3 pacientes operados / Partial splenectomy: report of three surgical patients

Se revisaron 3 historias clínicas de pacientes afectados de quistes esplénicos a los cuales se les realizó esplenectomía parcial como método reciente de la cirugía conservadora del bazo. Las intervenciones se efectuaron en el Hospital Provincial Docente Clinicoquirúrgico de Villa Clara en un período de 2 años (1986-1987). Se detalla la técnica quirúrgica empleada y se informa que no se presentó ninguna complicación, principalmente la hemorragia. En esta cirugía no se reporta mortalidad

Cirugía conservadora del bazo: informe de 11 casos / Conservative surgery of the spleen: report of 11 cases

Se presenta el estudio de 11 pacientes a los cuales se les realizó cirugía conservadora como tratamiento de la lesión esplénica. En 10 casos se efectuó sutura de la elsión esplénica. En 1 caso la lesión era un quiste postraumático y se le practicó una esplenectomía parcial. En ninguno de los casos operados se presentó sangramiento posoperatorio, ni hubo mortalidad. La esplenorrafia es una técnica segura bajo ciertas circunstancia y puede ser beneficiosa al reducir el riesgo de la sepsis posesplenectomía

Cirugía conservadora del bazo. informe de 11 casos / Conservative surgery of the spleen: report of 11 cases

Se presenta el estudio de 11 pacientes a los cuales se les realizó cirugía conservadora como tratamiento de la lesión esplénica. En 10 casos se efectuó sutura de la elsión esplénica. En 1 caso la lesión era un quiste postraumático y se le practicó una esplenectomía parcial. En ninguno de los casos operados se presentó sangramiento posoperatorio, ni hubo mortalidad. La esplenorrafia es una técnica segura bajo ciertas circunstancia y puede ser beneficiosa al reducir el riesgo de la sepsis posesplenectomía (AU)