Metformin Inhibits Zika Virus Infection in Trophoblast Cell Line.

Zika virus (ZIKV) infections have been associated with severe clinical outcomes, which may include neurological manifestations, especially in newborns with intrauterine infection. However, licensed vaccines and specific antiviral agents are not yet available. Therefore, a safe and low-cost therapy is required, especially for pregnant women. In this regard, metformin, an FDA-approved drug used to treat gestational diabetes, has previously exhibited an anti-ZIKA effect in vitro in HUVEC cells by activating AMPK. In this study, we evaluated metformin treatment during ZIKV infection in vitro in a JEG3-permissive trophoblast cell line. Our results demonstrate that metformin affects viral replication and protein synthesis and reverses cytoskeletal changes promoted by ZIKV infection. In addition, it reduces lipid droplet formation, which is associated with lipogenic activation of infection. Taken together, our results indicate that metformin has potential as an antiviral agent against ZIKV infection in vitro in trophoblast cells.

Therapeutic strategies and clinical evolution of patients with infantile fibrosarcoma: a unique paediatric case series.

BACKGROUND: Infantile fibrosarcoma is the most frequent soft tissue sarcoma in newborns or children under one year of age. This tumour often implies high local aggressiveness and surgical morbidity. The large majority of these patients carry the ETV6-NTRK3 oncogenic fusion. Hence, the TRK inhibitor larotrectinib emerged as an efficacious and safe alternative to chemotherapy for NTRK fusion-positive and metastatic or unresectable tumours. However, real-world evidence is still required for updating soft-tissue sarcoma practice guidelines. OBJECTIVE: To report our experience with the use of larotrectinib in pediatric patients. METHODS: Our case series shows the clinical evolution of 8 patients with infantile fibrosarcoma under different treatments. All patients enrolled in this study received informed consent for any treatment. RESULTS: Three patients received larotrectinib in first line. No surgery was needed with larotrectinib, which led to the rapid and safe remission of tumours, even in unusual anatomical locations. No significant adverse effects were observed with larotrectinib. CONCLUSION: Our case series supports that larotrectinib may be a therapeutic option for newborn and infant patients with infantile fibrosarcoma, especially in uncommon locations.

Primary splenic angiosarcoma. An aggressive and infrequent pathology.

Splenic angiosarcoma is a very rare and aggressive neoplasm originating from the splenic vascular endothelium whose prognosis is very poor despite surgical treatment. Preoperative diagnosis using imaging tests is a challenge due to its similarity to other vascular splenic tumors. The most common treatment is splenectomy, although it is rarely curative because of the aggressive and metastatic nature of the disease.

Cultivo primario de Helicobacter pylori a partir de biopsias gástricas obtenidas por endoscopia / Primary culture of Helicobacter pylori from endoscopic gastric biopsies

Objetivo: Determinar la viabilidad del cultivo de la bacteria Helicobacter pylori en Costa Rica por medio de la documentación de toma de muestras, la comparación del diagnóstico histopatológico y la descripción de los diagnósticos asociados a los aislamientos obtenidos con los resultados de la ureasa rápida. Métodos: Investigación descriptiva que involucró a pacientes de entre los 35 y 70 años, de ambos sexos, que asistieron al Servicio de Endoscopia Digestiva del Hospital Clínica Bíblica entre febrero y junio del 2019 para estudio gastroscópico. Se obtuvieron biopsias gástricas para diagnóstico histopatológico, prueba de ureasa rápida y cultivo de Helicobacter pylori. Para este último, se transportaron las biopsias en un medio de transporte semisólido, se maceró el tejido y se cultivó enagar Skirrow y agar selectivo para Helicobacter; una placa de cada medio se incubó a 37 °C en microaerofilia entre 48 horas y 10 días. La positividad del cultivo se realizó por observación de la morfología colonial y la bacteria se identificó por análisis microscópico al fresco, tinción de Gram y pruebas bioquímicas (catalasa, ureasa y oxidasa). Resultados: Se incluyó a 44 pacientes (edad: 50.6 ± 10.0, 54.5% masculinos). Se recuperó Helicobacter pylori en biopsias de 27 pacientes (61.4% de éxito). La recuperación de la bacteria fue similar en el medio Skirrow y en el selectivo para Helicobacter. El porcentaje de éxito de recuperación semanal aumentó durante el estudio hasta alcanzar un éxito del 100% en la semana 11. Se comparó el cultivo con la ureasa rápida en 27 pacientes y la concordancia entre ambos métodos fue de un coeficiente kappa de Cohen de 0.48. El cultivo detectó la bacteria en un 56% de los pacientes, la ureasa rápida en un 37% y la combinación de ambas técnicas permitió la detección en un 60%. El diagnóstico endoscópico más frecuente en los pacientes con cultivo positivo fue la gastritis eritematosa y gastritis crónica superficial y el diagnóstico histopatológico predominante fue gastritis crónica con atrofia gástrica. El diagnóstico por cultivo coincidió con la detección por azul de toluidina en un 80.4% de los casos. Conclusiones: Se puede implementar el cultivo de Helicobacter pylori en Costa Rica. Este estudio tuvo un porcentaje de recuperación de la bacteria de 61.4%. La combinación del método de cultivo con la prueba de ureasa rápida y la detección histológica contribuye a un diagnóstico certero y oportuno. Recomendamos que, con base en protocolos descritos en esta investigación, cada laboratorio estandarice las condiciones que le permitan un buen porcentaje de recuperación y una implementación adaptada a sus actividades de rutina.

Aim: To document the recent experiences on the implementation of sampling and culturing Helicobacter pylori in Costa Rica, to compare it with other diagnostic methods: rapid urease test and histopathology and to describe the diagnoses associated with the obtained isolates. Methods: Descriptive research involving patients who visited the digestive endoscopy department of the Clínica Bíblica hospital in San José, Costa Rica between February and July of 2019 for gastroscopy. Gastric biopsies were obtained and histopathological analysis, rapid urease test, and bacteriological culture for Helicobacter pylori were performed. For culture techniques, the sample was transported in an in-house semi-solid medium. Biopsy fragments were macerated and plated on Skirrow agar and Helicobacterselective in-house agar, and incubated in microaerophilic atmosphere for 48 hours to 10 days. Culture positivity was determined by observation of the colonial morphology and microscopic observation; Gram staining and biochemical tests (urease, catalase, and oxidase) were used for bacterial identification. Results: 44 patients (mean aged 50.6 ± 10.0 years old, 54.5% male) were included in the study. Helicobacter pylori was recovered in biopsies from 27 patients (61.4% success rate). Bacterial growth was similar regardless the culture medium, but the physiological state of the bacteria was better in the Helicobacter-selective agar than in Skirrow. The weekly recovery rate increased to reach a 100% recovery plateau on week 11. Culture was compared with the rapid urease test in 27 patients, and the concordance between both methods using Cohen's kappa coefficient was 0.48. Whilst the culture detected Helicobacter pylori in 56% of the patients, and the rapid urease test in 37%, the combination of both allowed a 60% rate. The most frequent endoscopic diagnosis in patients with positive cultures were erythematous gastritis and chronic superficial gastritis, and the predominant histopathological diagnosis was chronic atrophic gastritis. Culture-based diagnosis was consistent with the histopathology detection of Helicobacter pylori in 80.4% of the cases. Conclusions: The implementation of H. pylori culture in Costa Rica is possible. This study had a 61.4% recovery rate. The combination of culture with rapid urease test and histopathology increases the probability of an accurate and timely diagnosis. We recommend that, based on previously described protocols such as ours, each laboratory adjusts the conditions to allow a good recovery rate and implement H. pylori diagnostic methods most suitable to their routine activities.

Neonatal Intrathoracic Gastric Volvulus in Marfan's Syndrome.

We report a 12-day-old male who was admitted with vomiting because of an unusual early complication of Marfan's syndrome (MS): a sliding hiatal hernia. Initial ultrasound showed no stomach at its normal position and the chest X-ray presented an intrathoracic gas bubble with the nasogastric tube inside. An upper gastrointestinal contrast study confirmed the complete herniation of the stomach into the thorax. Via an exploratory laparotomy it was carefully reintroduced into the abdomen, following a hiatal reconstruction. A Thal fundoplication and a gastrostomy were also performed to guarantee its fixation. Although characterized by cardiac/aortic abnormalities, MS should be considered in any infant with hiatal/paraesophageal hernia, which should be repaired early to avoid gastric ischemia/volvulus.

Surgical Emergencies in Intestinal Venous Malformations.

BACKGROUND: Venous malformations (VMs) can occur in any part of the body; however, the gastrointestinal tract is a frequent location. These are usually asymptomatic, thus, representing a challenge to diagnosis. Intestinal location of VMs can be associated with severe complications that ultimately require an emergency surgery. Our aim was to analyze all patients with an intestinal VM with special focus on those who required emergency surgery. MATERIALS AND METHODS: A retrospective study of patients presenting complication caused by intestinal VM was performed. Clinical records, associated anomalies, physical findings, and treatment were assessed. RESULTS: Twenty-one patients had a diagnosis of intestinal VM, 16 (76%) were associated to blue rubber bleb nevus syndrome (BRBNS) and 5 (24%) were isolated. Only four (19%) of the total cases presented an episode of acute abdomen with hemodynamic instability that required an emergency surgery. Findings included two gastrointestinal bleedings, one volvulus, and one intussusception of small bowel. All patients underwent an uneventful recovery and are presently doing well. CONCLUSION: Intestinal VM can be challenging to diagnose in emergency situations, such as gastrointestinal situation or acute abdomen. The complications associated with it must be kept in mind, regardless of its low incidence.

Advantages of Cardiac Magnetic Resonance Imaging for Severe Pectus Excavatum Assessment in Children.

AIM: Cardiac function can be impaired in patients with pectus excavatum (PE) due to anatomic and dynamic compression of the heart. Efforts for radiation dose reduction in imaging techniques have allowed cardiac magnetic resonance imaging (c-MRI) to play a major role in PE assessment. The aim of our study is to describe the findings of c-MRI 18 months after we changed the PE assessment protocol from chest computed tomography to c-MRI. PATIENTS AND METHODS: Since mid-2015 all patients with severe PE (suspected Haller's index > 3.2) were assessed with inspiratory and expiratory c-MRI. A retrospective analysis of these patients was performed evaluating the following parameters: (1) Radiologic PE indexes (Haller's, correction and asymmetry indexes; and sternal rotation) and (2) cardiac function (including left and right ventricle ejection fraction). RESULTS: A total of 20 patients met the inclusion criteria. Dynamic imaging showed a significant difference during inspiration and expiration of the Haller's index 3.85 (range: 3.17-7.3) versus 5.10 (range: 3.85-10.8) (p < 0.05), and correction index (26.86% vs. 36.84%, respectively, p < 0.05). The sternal rotation was 14.5 (range: 0-36). c-MRI analysis disclosed a right ventricle ejection fraction of 50.3%. (normal range: 61% [54-71%]). Echocardiographic imaging underestimated the functional repercussion of PE in all patients. CONCLUSION: Initial results show that PE assessment by c-MRI allows a radiation-free image of the chest wall deformity during the entire breathing process. Also, it permitted the evaluation of the influence of sternum impingement on cardiac function. These findings allowed us a careful surgical evaluation and preoperative planning.

Pitfalls in Diagnosis of Early-Onset Inflammatory Bowel Disease.

AIM: The onset of inflammatory bowel disease (IBD) in patients younger than the age of 5 years is rare. Moreover, when there is exclusive colonic inflammation, diagnosis can be challenging. Our aim was to describe the difficulties and pitfalls in the diagnosis of early-onset IBD (eoIBD) and their repercussions in treatment decisions. PATIENTS AND METHODS: Patients with eoIBD (Crohn's disease [CD], ulcerative, and unclassified colitis) treated at our center between 1990 and 2016 were studied retrospectively. Demographic, clinical, medical, and surgical treatment data were analyzed. RESULTS: A total of 19 patients were diagnosed with eoIBD at 21 (1-46) months of age. Bloody diarrhea, growth failure, and abdominal pain were present in 90, 42, and 16%, respectively. After 9 (1-62) months from the onset, patients were classified as ulcerative colitis (nine), CD (two), and unclassified colitis (eight). Unresponsiveness to medical treatment was observed in 10 and prompted surgical assessment. A partial colectomy was performed in one, and nine underwent a total colectomy (one end stoma and eight ileoanal anastomosis [IAA]). At least one surgical complication occurred in 80% and ultimately six patients with an IAA required an end stoma. Overtime, final diagnosis of 5 out of the 10 surgical patients changed due to biopsy findings, unresponsiveness to medical treatment, or extraintestinal and perianal manifestations. After a 12-year (1-22) follow-up, 57.9% of the diagnoses of all patients were modified. CONCLUSION: EoIBD poses a challenge due to ambiguous presentation and absence of specific diagnostic tests. Surgical evaluation is often needed and surgeons must be mindful of possible initial misdiagnosis, in addition to short- and long-term outcomes before deciding aggressive surgical measures as well as intestinal reconstruction.

Sirolimus in the Treatment of Vascular Anomalies.

Aim of the Study mTOR inhibitors are showing promising results in the management of vascular anomalies. Although current controlled trials remain to be completed, many individual experiences are being published. We present our series of children with complex vascular anomalies treated with sirolimus. Patients and Methods A retrospective review of 41 patients treated with sirolimus between January 2011 and December 2015 was performed: 15% (n = 6) had vascular tumors (4 kaposiform hemangioendotheliomas, 1 PTEN) and 85% (n = 35) had malformations (13 generalized lymphatic anomalies/Gorham-Stout diseases [GSD], 1 kaposiform lymphangiomatosis [KLA], 11 large lymphatic malformations (LMs) in critical areas, 2 lymphedemas, 4 venous malformations, and 4 aggressive arteriovenous malformations [AVM]). Several variables were collected: type of vascular anomaly, duration of treatment, dosage, response, and secondary effects. Results There was a female predominance (1.4:1). All patients received sirolimus, at initial dosage of 0.8 mg/m2/12 hour. Overall successful response rate was 80.4% of cases, presenting improvement in radiologic imaging and reduction of symptoms, at a median time of 10 weeks. Patients showing no response included four AVMs, one GSD, one LM, one KLA, and one unknown tumor. Sirolimus was well tolerated, even in neonates, with insignificant side effects. No patients had complete resolution and no patients worsened on therapy. Thirty patients remain under treatment at the present moment. Conclusion Sirolimus has become a new therapeutic option for patients with vascular anomalies that do not respond to other treatments. Unfortunately, important questions as what is the most appropriate dosage and for how long should the patient be treated remain unanswered. An international registry followed by customized controlled trials is mandatory to clarify the future of this therapy.

Características de la mortalidad materna en la región metropolitana 20 de San Pedro Sula, Cortés Honduras. C.A en el período 2012-2013

La Mortalidad materna (MM) es el resultado de diferentes factores que inciden afavor o en contra de tal situación, ya sean sociales, económicos, culturales, biológicos,ambientales, políticos, etc.La MM ha pasado de 182 por cada 100,000 N.V. en 1990 a 108 por 100,000 N.V. en 1997siendo desplazada del primer a un quinto lugar, como causa de muerte. A pesar de estasignificativa reducción, Honduras se ubica como uno de los países en Latino América conlas tasas más elevadas.El estudio “Características Sociodemográficas de la Mortalidad materna en la RegiónMetropolitana 20 de San Pedro Sula, Cortés Honduras. C.A en el período 2012-2013”, tuvocomo objetivo analizar la situación de la MM en esta región de salud que nos permitióproponer conclusiones y recomendaciones que puedan ser tomadas en cuenta en losprogramas y políticas regionales de salud materna.Es un estudio descriptivo y transversal aplicado a las muertes de mujeres por causarelacionada con el embarazo, parto o puerperio hasta los 40 días de postparto; encontrandode 21 expedientes únicamente 6 casos por causa obstétrica directa y que fueron recolectadosa través de una guía de verificación, aplicada a los expedientes de las pacientes fallecidasen el período.El mayor porcentaje de MM por causas directas estaban comprendidas en menores de 19años y 19 a 24 años, la mitad habían cursado primaria completa y no se reporta niveleducativo superior, la mayoría de ellas en otras ocupaciones y en segundo lugar realizandoactividades domésticas; la mayor procedencia es urbana. La mitad eran primigestas y elresto multíparas y el 50 % ocurrió entre la semana de gestación: 38 y 41 y en menorproporción entre la 28 a 37, 21 a 27 y menores de 20...

Influence of Size on the Microstructure and Mechanical Properties of an AISI 304L Stainless Steel-A Comparison between Bulk and Fibers.

In this work, the mechanical properties and microstructural features of an AISI 304L stainless steel in two presentations, bulk and fibers, were systematically studied in order to establish the relationship among microstructure, mechanical properties, manufacturing process and effect on sample size. The microstructure was analyzed by XRD, SEM and TEM techniques. The strength, Young's modulus and elongation of the samples were determined by tensile tests, while the hardness was measured by Vickers microhardness and nanoindentation tests. The materials have been observed to possess different mechanical and microstructural properties, which are compared and discussed.

Seroprevalence of Bartonella spp. infection in HIV patients in Catalonia, Spain.

BACKGROUND: Although the first clinical descriptions of Bartonella infection were associated with immunocompromised patient with bacillary angiomatosis, we currently know that this organism is directly involved in diseases affecting a large number of patients, regardless of their immune status. Cat scratch disease, hepatic peliosis, and some cases of bacteraemia and endocarditis, are directly caused by some species of the genus Bartonella. The purpose of this study was to determinate the prevalence of IgG antibodies against Bartonella henselae and B. quintana in HIV patients and to identify the epidemiological factors involved. METHODS: Serum samples were collected from HIV patients treated at Hospital de Sabadell. Antibodies to B. henselae and B. quintana from 340 patients were examined by indirect immunofluorescence assay (IFA). Significance levels for univariate statistical test were determined by the Mann-Whitney U test and chi2 test. RESULTS: Of 340 patients, 82 were women and 258 men, with a median age of 42.21 +/- 10.35 years (range 16-86 years). Seventy-six (22.3%) patients reacted with one or more Bartonella antigens. Of all the factors concerning the seroprevalence rate being studied (age, sex, intravenous drugs use, alcohol consumption, CD4 levels, AIDS, HCV, HBV, residential area), only age was statistically significant. CONCLUSION: A high percentage of HIV patients presents antibodies to Bartonella and is increasing with age.

Role of weight-based ribavirin dosing and extended duration of therapy in chronic hepatitis C in HIV-infected patients: the PRESCO trial.

The response to pegylated interferon (pegIFN) plus ribavirin (RBV) as treatment of chronic hepatitis C virus (HCV) infection is lower in HIV-coinfected than in HCV-monoinfected patients and could be due to suboptimal RBV dosing and/or insufficient duration of therapy in prior trials. In a prospective, multicenter, open, comparative trial, HCV/HIV-coinfected patients received pegIFN plus weight-based RBV for 48 or 72 weeks (HCV genotypes 1 and 4) and 24 or 48 weeks (HCV genotypes 2 and 3). Use of didanosine was not allowed. Out of 389 patients included in the trial, 61% were infected by HCV-1/4 and 67% had serum HCV-RNA >500,000 IU/ml. Sustained virological response (SVR) was achieved by 49.6%, significantly higher in HCV-2/3 than HCV-1/4 (72.4% vs. 35%; p < 0.0001). A high drop-out rate in the longer treatment arms precluded obtaining definitive conclusions about the efficacy of prolonging therapy. Premature treatment discontinuations due to serious adverse events occurred in 8.2%. Infection with HCV-2/3, lower baseline HCV-RNA, and negative HCV-RNA at week 12 were all independent predictors of SVR in the multivariate analysis. The use of RBV 1000-1200 mg/day plus pegIFN is relatively safe and provides SVR in nearly half of coinfected patients, twice as high in HCV-2/3 than HCV-1/4.

[Clinical and epidemiological study of a series of HIV-infected patients over 50 years old]. / Estudio de una serie clínica de pacientes infectados por el VIH mayores de 50 años.

INTRODUCTION: The epidemiology of human immunodeficiency virus (HIV) infection has changed in recent years. Cases in persons over the age of 50 have increased, and the most frequent mode of transmission is sexual contact. The objective of this study is to analyse the epidemiological, clinical and evolution characteristics of a clinical series of HIV-infected patients over 50 years old at the time of diagnosis. METHODS: 165 HIV-infected patients over the age of 50, attended at Hospital Clinic (Barcelona) and Corporació Parc Taulí (Sabadell) during the period of 1985 to 2001, were studied. RESULTS: Among the total, 81% of the patients were men, mean age at the time of diagnosis was 58.5 years, and 81.8% had acquired the disease by sexual contact. The median initial CD4 T cell count was 216 cells/microl. Initial viral load was 1,000-100,000 copies/ml in 45.2% of the patients, whereas 52.3% had > 100,000 copies/ml. At the time of diagnosis, 30.9% had an AIDS-defining disease. The main opportunistic diseases were pulmonary tuberculosis, Kaposi's sarcoma, P. jiroveci (before carinii) pneumonia and non-Hodgkin lymphoma. Mortality due to AIDS was 32.7%. CONCLUSIONS: Subjects over 50 years old diagnosed with HIV-infection were predominantly men, who acquired the infection by sexual contact. A high percentage of patients were diagnosed with the development of an opportunistic disease.

Recurrent stroke as a manifestation of primary angiitis of the central nervous system in a patient infected with human immunodeficiency virus.

CONTEXT: Cerebral vasculitis in patients infected with human immunodeficiency virus (HIV) is usually related to additional or secondary infectious agents other than neoplastic diseases or HIV itself. OBJECTIVE: To describe a 31-year-old patient infected with HIV who presented with 2 recurrent, acute episodes of neurologic impairment in a 5-month period. DESIGN: Comparison of clinical and histologic data between the present case and previously published cases. SETTING: Community hospital. PATIENT: A 31-year-old, HIV-infected patient with recurrent strokes and chronic lymphocytic meningitis. INTERVENTION: After ruling out cardiac embolisms and coagulation disorders, the presence of central nervous system vasculitis, probably secondary to an infectious process, was suspected based on the clinical examination and cerebrospinal fluid abnormalities. RESULTS: Necropsy findings suggest the diagnosis of primary angiitis of the central nervous system, and the only infectious agent that could be found was HIV. CONCLUSIONS: Histologic studies were compatible with a diagnosis of primary angiitis of the central nervous system, but the pathogenic role of HIV in the genesis of the vasculitic process cannot be elucidated.

Incidencia de cáncer gástrico temprano en Costa Rica. Resultados de un quinquenio en hospitales del área metropolitana / Incidence of gastric cancer in Costa Rica. Results of a period of five years in hospitals of metropolitan area

A lo largo del quinquenio 1986-1990 en las unidades de endoscopía de los tres hospitales de adultos del área metropolitana fueron diagnosticados 1536 casos de adenocarcinoma gástrico. De ellos, se encontró que en 103 pacientes el tumor se localizó en mucosa o en submucosa sin interesar la capa muscular propia. La distribución de estos tumores fue de 66 hombres y 37 en mujeres con una relación de 1.7/1. Además el tumor aumentó marcadamente entre los 51 a los 80 años y como ha sido descrito en los países de alta frecuencia de este cáncer, la variedad intestinal fue la más frecuente con su mayor localización de 51.4 por ciento en región antropilórica. Debe hacerse énfasis que a través de los 5 años del estudio el porcentaje de tumores avanzados respecto a los localizados hasta la submucosa se mantuvo estacionario, con valor promedio del 6.7 por ciento. Por consiguiente es necesario implementar las campañas de detección en grandes masas de población con tecnología de menor costo y que las personas con algún signo de positividad sean tributarias de endoscopía que es el método óptimo pero desgraciadamente de alto costo