Whole-genome sequencing of Klebsiella pneumoniae MDR circulating in a pediatric hospital setting: a comprehensive genome analysis of isolates from Guayaquil, Ecuador.

BACKGROUND: Klebsiella pneumoniae is the major cause of nosocomial infections worldwide and is related to a worsening increase in Multidrug-Resistant Bacteria (MDR) and virulence genes that seriously affect immunosuppressed patients, long-stay intensive care patients, elderly individuals, and children. Whole-Genome Sequencing (WGS) has resulted in a useful strategy for characterizing the genomic components of clinically important bacteria, such as K. pneumoniae, enabling them to monitor genetic changes and understand transmission, highlighting the risk of dissemination of resistance and virulence associated genes in hospitals. In this study, we report on WGS 14 clinical isolates of K. pneumoniae from a pediatric hospital biobank of Guayaquil, Ecuador. RESULTS: The main findings revealed pronounced genetic heterogeneity among the isolates. Multilocus sequencing type ST45 was the predominant lineage among non-KPC isolates, whereas ST629 was found more frequently among KPC isolates. Phylogenetic analysis suggested local transmission dynamics. Comparative genomic analysis revealed a core set of 3511 conserved genes and an open pangenome in neonatal isolates. The diversity of MLSTs and capsular types, and the high genetic diversity among these isolates indicate high intraspecific variability. In terms of virulence factors, we identified genes associated with adherence, biofilm formation, immune evasion, secretion systems, multidrug efflux pump transporters, and a notably high number of genes related to iron uptake. A large number of these genes were detected in the ST45 isolate, whereas iron uptake yersiniabactin genes were found exclusively in the non-KPC isolates. We observed high resistance to commonly used antibiotics and determined that these isolates exhibited multidrug resistance including ß-lactams, aminoglycosides, fluoroquinolones, quinolones, trimetropins, fosfomycin and macrolides; additionally, resistance-associated point mutations and cross-resistance genes were identified in all the isolates. We also report the first K. pneumoniae KPC-3 gene producers in Ecuador. CONCLUSIONS: Our WGS results for clinical isolates highlight the importance of MDR in neonatal K. pneumoniae infections and their genetic diversity. WGS will be an imperative strategy for the surveillance of K. pneumoniae in Ecuador, and will contribute to identifying effective treatment strategies for K. pneumoniae infections in critical units in patients at stratified risk.

Diabetes gestacional: conceptos actuales / Gestational diabetes: Current concepts

Resumen OBJETIVO: exponer los conceptos más actualizados de diabetes y embarazo. MÉTODO: búsqueda en PubMed y Lilacs de artículos de revisión publicados en inglés o español entre los años 2001 y 2016 con los términos "diabetes mellitus", "diabetes gestacional", "diabetes y embarazo". RESULTADOS: se encontraron 525 artículos. El consenso total de los principales temas de diabetes y embarazo se concentra en las últimas 27 revisiones y 7 guías clínicas, que son la base de esta revisión. La diabetes gestacional se asocia con mayor riesgo de preeclampsia, de posibilidad de cesárea, macrosomía, distocia de hombros y mortalidad perinatal. Está demostrado que el primer paso en el tratamiento de la diabetes es la dieta adecuada y luego la insulina o metformina. La gliburida no debe indicarse para el control de la diabetes gestacional. CONCLUSIONES: la diabetes gestacional sigue siendo una de las principales complicaciones obstétricas con alta tasa de morbilidad materna, neonatal y pediátrica. El tratamiento debe enfocarse a la dieta como primera medida y, de ser necesario, una estrategia farmacológica de metformina e insulina como únicas opciones.

Abstract OBJECTIVE: To present the most up-to-date concepts of diabetes and pregnancy. METHOD: PubMed and lilacs search articles published in english or spanish between 2001 and 2016 with the terms "diabetes mellitus", "gestational diabetes", "diabetes and pregnancy". RESULTS: 525 articles were found. The overall consensus on the major issues of diabetes and pregnancy is concentrated in the last 27 reviews and 7 clinical guidelines, which are the basis of this review. Gestational diabetes is associated with an increased risk of preeclampsia, caesarean section, macrosomia, shoulder dystocia and perinatal mortality. It is proven that the first step in the treatment of diabetes is the proper diet and then insulin or metfomine. Glyburide should not be indicated for the management of gestational diabetes. CONCLUSIONS: Gestational diabetes continues to be one of the main obstetric complications with a high rate of maternal, neonatal and pediatric morbidity. Treatment should focus on diet as a first step and, if necessary, a pharmacological strategy of metformin and insulin as the only options.

Enzalutamide as monotherapy for advanced prostate cancer: why not? / Enzalutamida como monoterapia para cáncer de próstata avanzado: ¿por qué no?

OBJECTIVES: Prostate cancer (PCa) is an androgen-dependent disease. In some cases, the tumor progresses despite castration levels of serum testosterone, turning into the lethal phenotype of castration-resistant prostate cancer (CRPC), still driven by androgens and requiring the androgen receptor as a driver and responsible for progression. Enzalutamide, an androgen receptor inhibitor, is indicated for the treatment of metastatic CRPC, asymptomatic or mildly symptomatic, after failure of androgen deprivation. In both clinical trials that led to its approval, Enzalutamide was administered with an LHRH analog, setting the "standard of care" for its use. In this article we evaluate the available evidence and theory on the use of Enzalutamide as monotherapy. METHODS: Androgen deprivation well-known adverse events, together with the fact that its clinical benefit is moderate and the evidence strength is weak, and the direct negative impact on the common chronic conditions affecting this age-group led to investigation of Enzalutamide without LHRH analogs. RESULTS: There are clinical trials on Enzalutamide monotherapy for hormone-sensitive prostate cancer with favourable outcomes, and there are also two ongoing studies in different advanced PCa scenarios, the PROSPER and EMBARK trials. It would be up to now a safe alternative, with less toxicity and lower costs. CONCLUSION: It is mandatory to validate these early results on the use on Enzalutamide monotherapy for advanced prostate cancer, hormone-sensitive or castration resistant, metastatic or not, but in the meantime, we wonder, why not?

Acalculous cholecystitis in a patient with Plasmodium falciparum infection after a trip to the Dominican Republic.

Acalculous cholecystitis has been associated with several infectious agents, but its relation with Plasmodium falciparum infection has not been clearly defined. This is the first case of acalculous cholecystitis produced by Plasmodium falciparum infection that is directly documented and should be included among the differential diagnoses of acalculous cholecystitis.

Tumor renal bilatareal asincrónico / Asinchronic renal bilateral tumor

Paciente de 61 años de edad a quien se le realizó nefrectomía derecha en 1991 por tumor de polo superior (carcinorna renal de células claras). Comienza con terapia inmunomoduladora con control durante 1.5 año perdiéndose el paciente hasta 1995 en que vuelve a la consulta por tumoración palpable en hipocondrio izquierdo. Los estudios revelaron tumor sólido de 6 cm en región media y polo inferior del riñón izquierdo. Se comenzó tratamiento con interleukina y 5-fluoracilo con los controles necesarios por T.A.C. que mostraban reducción del tamaño tumoral. Actualmente continúa con la misma terapia más ciclos de vimblastina observando disminución importante del tamaiío tumoral que permitiría en un futuro realizar nefrectomía parcial o tumorectomía

Prognostic value of the strict criteria: an Argentinian experience.

The prognostic value of normal sperm morphology, evaluated according to the strict criteria, was prospectively assessed. The study included 112 IVF cycles. The percentage normal sperm morphology of the semen samples used in each cycle was determined and assigned to one of three prognostic groups; P-pattern (< 4% normal forms), G-pattern (5-8% normal forms), and N-pattern (> 8% normal forms). The fertilization, grade 4 embryo attainment, and pregnancy rates were compared between the three groups. The fertilization rate of the N-pattern group (83.7%) was significantly higher than that of the G-pattern (59.65%) and the P-pattern (22.58%) groups. The grade 4 embryo attainment rate was only significantly different between the N-pattern (23.38%) and the P-pattern (4.76%) groups. No pregnancy was obtained in the P-pattern group compared to a pregnancy rate per transfer of 23.08% in the N-pattern group. This study reaffirms the interlaboratory reproducibility and the prognostic value of normal sperm morphology.

Discordancia entre la determinación morfológica realizada con criterio estricto y normas de la Organización Mundial de la Salud (OMS) / Disagreement between morphologic determination made with stric criterion and WHO 'standards

Debido a la falta de correlación entre estudios básicos del semen, como espermatograma, y los resultados en fertilización asistida, se han desarrollado numerosos tests para evaluar la capacidad fecundante del semen. Entre ellos, la determinación de las formas morfológicamente normales ha tenido un gran desarrollo. Por este motivo, quisimos comparar retrospectivamente dos criterios de evaluación morfológica: Criterio Estricto (CE) y las normales dadas por la Organización Mundial de la Salud (OMS). Cuando la morfología espermática se encuentra muy alterada ("patrón P", CE < 4 por ciento), la evaluación morfológica con criterio OMS podría tener un valor predictivo. En todos los demás casos, la discordancia promedio de 19,6 por ciento, indicaría la necesidad de la determinación morfológica con Criterio Estricto. En nuestro Centro, el Criterio Estricto se correlaciona con los resultados en fertilización asistida

Discordancia entre la determinación morfológica realizada con criterio estricto y normas de la Organización Mundial de la Salud (OMS) / Disagreement between morphologic determination made with stric criterion and WHO standards

Debido a la falta de correlación entre estudios básicos del semen, como espermatograma, y los resultados en fertilización asistida, se han desarrollado numerosos tests para evaluar la capacidad fecundante del semen. Entre ellos, la determinación de las formas morfológicamente normales ha tenido un gran desarrollo. Por este motivo, quisimos comparar retrospectivamente dos criterios de evaluación morfológica: Criterio Estricto (CE) y las normales dadas por la Organización Mundial de la Salud (OMS). Cuando la morfología espermática se encuentra muy alterada ("patrón P", CE < 4 por ciento), la evaluación morfológica con criterio OMS podría tener un valor predictivo. En todos los demás casos, la discordancia promedio de 19,6 por ciento, indicaría la necesidad de la determinación morfológica con Criterio Estricto. En nuestro Centro, el Criterio Estricto se correlaciona con los resultados en fertilización asistida (AU)

Effects of phenytoin administration on murine immune function.

The results obtained in these series of experiments indicate that oral administration of phenytoin (100, 50, or 25 mg/kg) to mice significantly depressed both humoral and cellular immune responses, evaluated by the techniques of enumeration of direct and indirect spleen plaque-forming cells (PFC) and the delayed-type hypersensitivity reaction (DTH) against sheep red blood cells (SR BC), when compared with those observed in normal control animals. Furthermore, spleen cells, purified splenic T lymphocytes or Ly 2 + T cells obtained from 100 mg/kg phenytoin-treated donor mice were capable of diminishing both PFC and DTH responses of normal cells transferred into lethally irradiated mice. The immunodepressor effect of phenytoin was observed despite the fact that administration of this drug induced a rise in spleen cellularity.