Genética y ambiente en la embriogénesis de la secuencia sirenomelia, reporte de un caso

Introduction: the sirenomelia sequence is a primary defect that occurs in the mesoderm of the posterior middle axis of the embryo and turns out the fusion of the primordium of limbs in its fibular margins, with absence or complete development of the intercurrent caudal structures.Case report: a 36-year-old pregnant woman with a reproductive history of three previous pregnancies and two deliveries without abortions, who in the genetic risk assessment consultation, classified as increased genetic risk (risk of chromosomal alterations). A history of possible exposure to teratogens was collected. Multiple congenital defects were observed in the study of the fetus by means of ultrasound. Genetic counseling and reproductive options are provided in multidisciplinary team office to both members of the couple. Both gave their consent for the interruption of pregnancy. The pathological study confirmed multiple congenital anomalies.Conclusions: major congenital anomalies, that are part of the sirenomelia sequence, can be diagnosed in the prenatal stage by means of Ultrasonography Studies during the first and second trimesters of pregnancy. The definitive and classified diagnosis can be completed after the pathological study of the fetus.  Genetic counseling is improved and based on the consideration of the alterations in embryogenesis with its genetic and environmental aspects; where the concluding aspects are personalized considering the pregnant woman, her family, as well as her social and personal situation.Introducción: la secuencia sirenomelia es un defecto primario que ocurre en mesodermo del eje medio posterior del embrión y produce la fusión de los primordios de miembros en sus márgenes fibulares, con ausencia o desarrollo completo de las estructuras caudales intercurrentes.Presentación de caso: gestante de 36 años, con una historia reproductiva de tres gestaciones, dos partos y ningún aborto. En la consulta de evaluación de riesgo genético se clasificó como riesgo genético incrementado (riesgo de alteraciones cromosómicas). Se recoge el antecedente de posible exposición a teratógenos. Por el estudio del feto mediante el uso del ultrasonido se observan defectos congénitos múltiples. Se brinda asesoramiento genético y opciones reproductivas en consulta multidisciplinaria a ambos miembros de la pareja. Ambos ofrecen sus consentimientos para la interrupción de la gestación. Se realiza el estudio anatomopatológico en el cual se reportan múltiples defectos congénitos.Conclusiones: Los defectos congénitos mayores que forman parte de la secuencia sirenomelia, son posibles diagnosticarlos, en la etapa prenatal, mediante la ultrasonografía del primer y segundo trimestre de la gestación. El diagnóstico definitivo, clasificado, puede ser concluido después del estudio anatomopatológico fetal.  El asesoramiento genético se enriquece y se fundamenta si se tiene en cuenta las alteraciones en la embriogénesis con sus aspectos genéticos y ambientales, estos últimos personalizados según la gestante y su entorno familiar, social y personal

Sospecha prenatal y diagnóstico postnatal de un paciente con fibrosis quística

Introduction: Cystic fibrosis is a genetic disease of autosomal recessive inheritance, characterized by dysfunction of the exocrine secretion glands.Case report: Male patient 2 years of age, at term (39 weeks). In the third trimester of pregnancy, polyhydramnios, dilated bowel loops and a possible low bowel atresia is not ruled out at that time. Rest of normal genetic tests. At the month of birth he enters due to malnutrition and liquid diarrhea. After 2 months, she re-entered due to respiratory manifestations, in the nutritional evaluation her height and weight was below the third percentile, she had skin-pale pallor, demonstrating anemia due to iron deficiency and light hair color. Given the prenatal history and the predominance of digestive and respiratory manifestations, it is decided to perform sweat electrolyte examination in 2 moments, which are negative. It is decided to conduct a molecular study for the detection of mutations that results: ΔF508del / R1162X (Heterozygous compound for cystic fibrosis). Dietary and vitamin therapy treatment is applied. He continues his attention in multidisciplinary consultations, Nutrition, Gastroenterology, Genetics and Pediatrics.Conclusions: The early diagnosis of cystic fibrosis is made by detecting the cardinal signs that involve the respiratory and digestive system; as well as family history. In the prenatal stage, the findings related to the increased amniotic fluid, the alteration of the fetal vesicle should be taken into account, which allows the definitive diagnosis to be made by studying the mutations.Introducción: La fibrosis quística es una enfermedad genética de herencia autosómica recesiva, caracterizada por disfunción de las glándulas de secreción exocrina.Presentación del caso: Paciente masculino de 2 años de edad, a término (39 semanas). En el tercer trimestre del embarazo, se reporta por ultrasonido polihidramnios, asas intestinales dilatadas, ecorrefrigencia abdominal grado III, no descartándose en esos momentos una posible atresia intestinal baja. Resto de exámenes genéticos normales. Al mes de nacido ingresa por desnutrición y diarreas liquidas. A los 2 meses reingresa por manifestaciones respiratorias, en la evaluación nutricional su peso para la talla se encontraba por debajo del tercer percentil, tenía palidez cutáneomucosa, demostrándose anemia por déficit de hierro y coloración clara del pelo. Ante los antecedentes prenatales y el predominio de manifestaciones digestivas y respiratorias, se decide realizar examen de electrolitos en sudor en 2 momentos, los que resultan negativos. Se decide realizar estudio molecular para detección de mutaciones que resulta: ΔF508del/R1162X (Heterocigoto compuesto para la fibrosis quística). Se pone tratamiento dietético y con vitaminoterapia. Continúa su atención en consultas multidisciplinarias, de Nutrición, Gastroenterología, Genética y Pediatría.Conclusiones: El diagnóstico precoz de la fibrosis quística se realiza mediante la detección de los signos cardinales que involucran al sistema respiratorio y al digestivo; así como los antecedentes familiares. En la etapa prenatal se deben tener en cuenta los hallazgos relacionados con el líquido amniótico aumentado, la ecorrefrigencia abdominal, la alteración de la vesícula fetal lo cual permite realizar el diagnóstico definitivo mediante el estudio de las mutaciones

A clinical practice guideline for the management of the foot and ankle in rheumatoid arthritis

Rheumatoid arthritis causes progressive joint destruction in the long term, causing a deterioration of the foot and ankle. A clinical practice guideline has been created with the main objective of providing recommendations in the field of podiatry for the conservative management of rheumatoid arthritis. Thus, healthcare professionals involved in foot care of adults with rheumatoid arthritis will be able to follow practical recommendations. A clinical practice guideline was created includ- ing a group of experts (podiatrists, rheumatologists, nurses, an orthopaedic surgeon, a physiotherapist, an occupational therapist and patient with rheumatoid arthritis). Methodological experts using GRADE were tasked with systematically reviewing the available scientific evidence and developing the information which serves as a basis for the expert group to make recommendations. Key findings include the efficacy of chiropody in alleviating hyperkeratotic lesions and improv- ing short-term pain and functionality. Notably, custom and standardized foot orthoses demonstrated significant benefits in reducing foot pain, enhancing physical function, and improving life quality. Therapeutic footwear was identified as crucial for pain reduction and mobility improvement, emphasizing the necessity for custom-made options tailored to individual patient needs. Surgical interventions were recommended for cases which were non-responsive to conservative treatments, aimed at preserving foot functionality and reducing pain. Moreover, self-care strategies and education were underscored as essential components for promoting patient independence and health maintenance. A series of recommendations have been created which will help professionals and patients to manage podiatric pathologies derived from rheumatoid arthritis.Funding for open access publishing: Universidad Málaga/CBU

The synthetic molecule stauprimide impairs cell growth and migration in triple-negative breast cancer

Stauprimide, a semi-synthetic derivative of staurosporine, is known mainly for its potent differentiation-enhancing properties in embryonic stem cells. Here, we studied the effects of stauprimide in cell growth and migration of triple-negative breast cancer cells in vitro, evaluating its potential antitumoral activity in an orthotopic mouse model of breast cancer in vivo. Our results from survival curves, EdU incorporation, cell cycle analysis and annexin-V detection in MDA-MB-231 cells indicated that stauprimide inhibited cell proliferation, arresting cell cycle in G2/M without induction of apoptosis. A decrease in the migratory capability of MDA-MB-231 was also assessed in response to stauprimide. In this work we pointed to a mechanism of action of stauprimide involving the modulation of ERK1/2, Akt and p38 MAPK signalling pathways, and the downregulation of MYC in MDA-MB-231 cells. In addition, orthotopic MDA-MB-231 xenograft and 4T1 syngeneic models suggested an effect of stauprimide in vivo, increasing the necrotic core of tumors and reducing metastasis in lung and liver of mice. Together, our results point to the promising role of stauprimide as a putative therapeutic agent in triple-negative breast cancer.MRI experiments were performed in the ICTS “NANBIOSIS”, more specifically in the U28 Unit at the Andalusian Centre for Nanomedicine & Biotechnology (BIONAND). Cell cultures were performed in the Cell Culture Service at the Central Support Services of Research (SCAI) of the University of Málaga. // Partial funding for open access charge: Universidad de Málaga / CBUA

Reappraisal of the outcome of healthcare-associated and community-acquired bacteramia: a prospective cohort study

Background: Healthcare-associated (HCA) bloodstream infections (BSI) have been associated with worse outcomes, in terms of higher frequencies of antibiotic-resistant microorganisms and inappropriate therapy than strict community-acquired (CA) BSI. Recent changes in the epidemiology of community (CO)-BSI and treatment protocols may have modified this association. The objective of this study was to analyse the etiology, therapy and outcomes for CA and HCA BSI in our area. Methods: A prospective multicentre cohort including all CO-BSI episodes in adult patients was performed over a 3-month period in 2006–2007. Outcome variables were mortality and inappropriate empirical therapy. Adjusted analyses were performed by logistic regression. Results: 341 episodes of CO-BSI were included in the study. Acquisition was HCA in 56% (192 episodes) of them. Inappropriate empirical therapy was administered in 16.7% (57 episodes). All-cause mortality was 16.4% (56 patients) at day 14 and 20% (71 patients) at day 30. After controlling for age, Charlson index, source, etiology, presentation with severe sepsis or shock and inappropriate empirical treatment, acquisition type was not associated with an increase in 14-day or 30-day mortality. Only an stratified analysis of 14th-day mortality for Gram negatives BSI showed a statically significant difference (7% in CA vs 17% in HCA, p = 0,05). Factors independently related to inadequate empirical treatment in the community were: catheter source, cancer, and previous antimicrobial use; no association with HCA acquisition was found. Conclusion: HCA acquisition in our cohort was not a predictor for either inappropriate empirical treatment or increased mortality. These results might reflect recent changes in therapeutic protocols and epidemiological changes in community pathogens. Further studies should focus on recognising CA BSI due to resistant organisms facilitating an early and adequate treatment in patients with CA resistant BSI

HIV coinfection predicts failure of ledipasvir/sofosbuvir in treatment-naïve noncirrhotic patients with HCV genotype

The efficacy of licensed direct-acting antiviral (DAA) regimens is assumed to be the same for hepatitis C virus (HCV)–monoinfected patients (HCV-Mono) and HIV/HCV-coinfected patients (HCV-Co). However, the high sustained viral response (SVR) rates of DAA regimens and the small number of HIV-infected patients included in registration trials have made it difficult to identify predictors of treatment failure, including the presence of HIV. Methods. We compared treatment outcomes for ledipasvir/sofosbuvir (LDV/SOF) against HCV G1 in treatment-naïve HCV-Mono and HCV-Co without cirrhosis in a prospective registry of individuals receiving DAAs for HCV. Results. Up to September 2017, a total of 17 269 patients were registered, and 1358 patients (1055 HCV-Mono/303 HCV-Co) met the inclusion criteria. Significant differences between HCV-Mono and HCV-Co were observed for age, gender, and G1 subtype distribution. Among HCV-Co, 99.0% were receiving antiretroviral therapy. SVR rates for LDV/SOF at 8 weeks did not differ significantly between HCV-Mono and HCV-Co (96.9% vs 94.0%; P = .199). However, the SVR rate for LDV/SOF at 12 weeks was significantly higher for HCV-Mono than HCV-Co (97.2% vs 91.8%; P = .001). A multivariable logistic regression model including age, sex, liver stiffness, G1 subtype, HCV-RNA, HIV, and treatment duration showed the factors associated with treatment failure to be male sex (adjusted odds ratio [aOR], 2.49; 95% confidence interval [CI], 1.27–4.91; P = .008) and HIV infection (aOR, 2.23; 95% CI, 1.13–4.38; P = .020). Conclusions. The results of this large prospective study analyzing outcomes for LDV/SOF against HCV G1 in treatment-naïve noncirrhotic patients suggest that HIV infection is a predictor of treatment failure in patients with chronic hepatitis C.This work was supported by the Spanish AIDS Research Network (RD16/0025/0017), which is included in the Spanish I+D+I Plan and is co-financed by ISCIII-Subdirección General de Evaluacion and European Funding for Regional Development (FEDER), and the Fondo de Investigación de Sanidad en España (FIS)/Instituto de Salud Carlos III (Spanish Health Research Funds; PI17/00657)

Prevalence, features and predictive factors of liver nodules in Fontan surgery patients: The VALDIG Fonliver prospective cohort

Background & Aims: Fontan surgery is used to treat a variety of congenital heart malformations, and may lead to advanced chronic liver disease in the long-term. This study examines the prevalence, characteristics and predictors of liver nodules in patients following Fontan surgery. Methods: This was a prospective, cross-sectional, observational study conducted at 8 European centres. Consecutive patients who had undergone Fontan surgery underwent blood tests, abdominal ultrasonography (US), transient elastography (Fibroscan®), echocardiography, haemodynamic assessments, and abdominal MRI/CT scan. The primary outcome measure was liver nodules detected in the MRI/CT scan. Predictors of liver nodules were identified by multivariate logistic regression. Results: One hundred and fifty-two patients were enrolled (mean age 27.3 years). The mean time elapsed from surgery to inclusion was 18.3 years. Liver nodule prevalences were 29.6% (95% CI 23–37%) on US and 47.7% (95% CI 39–56%) on MRI/CT. Nodules were usually hyperechoic (76.5%), round-shaped (>80%), hyperenhancing in the arterial phase (92%) and located in the liver periphery (75%). The sensitivity and specificity of US were 50% (95% CI 38–62%) and 85.3% (95% CI 75–92%), respectively. Inter-imaging test agreement was low (adjusted kappa: 0.34). In the multivariate analysis, time since surgery >10 years was the single independent predictor of liver nodules (odds ratio 4.18; p = 0.040). Hepatocellular carcinoma was histologically diagnosed in 2 of the 8 patients with hypervascular liver nodules displaying washout. Conclusion: While liver nodules are frequent in Fontan patients, they may go unnoticed in US. Liver nodules are usually hyperechoic, hypervascular and predominantly peripheral. This population is at risk of hepatocellular carcinoma, the diagnosis of which requires confirmatory biopsy

Human Immunodeficiency Virus/Hepatits C Virus Coinfection in Spain: Elimination Is Feasible, but the Burden of Residual Cirrhosis Will Be Significant

Background: We assessed the prevalence of antibodies against hepatitis C virus (HCV-Abs) and active HCV infection in patients infected with human immunodeficiency virus (HIV) in Spain in 2016 and compared the results with those of similar studies performed in 2002, 2009, and 2015. Methods: The study was performed in 43 centers during October-November 2016. The sample was estimated for an accuracy of 2% and selected by proportional allocation and simple random sampling. During 2016, criteria for therapy based on direct-acting antiviral agents (DAA) were at least significant liver fibrosis, severe extrahepatic manifestations of HCV, and high risk of HCV transmissibility. Results: The reference population and the sample size were 38904 and 1588 patients, respectively. The prevalence of HCV-Abs in 2002, 2009, 2015, and 2016 was 60.8%, 50.2%, 37.7%, and 34.6%, respectively (P trend <.001, from 2002 to 2015). The prevalence of active HCV in 2002, 2009, 2015, and 2016 was 54.0%, 34.0%, 22.1%, and 11.7%, respectively (P trend <.001). The anti-HCV treatment uptake in 2002, 2009, 2015, and 2016 was 23.0%, 48.0%, 59.3%, and 74.7%, respectively (P trend <.001). In 2016, HCV-related cirrhosis was present in 7.6% of all HIV-infected individuals, 15.0% of patients with active HCV, and 31.5% of patients who cleared HCV after anti-HCV therapy. Conclusions: Our findings suggest that with universal access to DAA-based therapy and continued efforts in prevention and screening, it will be possible to eliminate active HCV among HIV-infected individuals in Spain in the short term. However, the burden of HCV-related cirrhosis will continue to be significant among HIV-infected individuals.This work was funded by grant Ref. no. GLD14-00279 from the GILEAD Fellowship Programme (Spain) and by the Spanish AIDS Research Network (RD16/0025/0017, RD16/0025/0018) that is included in the Spanish I+D+I Plan and is co-financed by ISCIII-Subdirección General de Evaluacion and European Funding for Regional Development (FEDER).S

Memoria del III Coloquio Internacional sobre Diversidad Cultural y Estudios Regionales

Del 05 al 07 de noviembre de 2014 se llevó a cabo en la Sede de Occidente de la Universidad de Costa Rica, el III Coloquio Internacional sobre Diversidad Cultural y Estudios Regionales, dicado a Julieta Dobles Izaguirre, Premio Nacional de Cultura Magón, 2013. Este III Coloquio Internacional fue organizado por el Centro de Investigaciones sobre Diversidad Cultural y Estudios Regionales (CIDICER), primer Centro de Investigaciones de una Sede Regional de la Universidad de Costa Rica. Se contó con personas investigacdoras nacionales e internacionales quienes presentaron sobre temas relacionados con la diversidad cultural y los estudios regionales.Universidad de Costa Rica/[836-B4-702]/UCR/Costa RicaUCR::Sedes Regionales::Sede de Occidente::Recinto San Ramón::Centro de Investigaciones sobre Diversidad Cultural y Estudios Regionales (CIDICER

Role of age and comorbidities in mortality of patients with infective endocarditis

[Purpose]: The aim of this study was to analyse the characteristics of patients with IE in three groups of age and to assess the ability of age and the Charlson Comorbidity Index (CCI) to predict mortality. [Methods]: Prospective cohort study of all patients with IE included in the GAMES Spanish database between 2008 and 2015.Patients were stratified into three age groups:<65 years,65 to 80 years,and ≥ 80 years.The area under the receiver-operating characteristic (AUROC) curve was calculated to quantify the diagnostic accuracy of the CCI to predict mortality risk. [Results]: A total of 3120 patients with IE (1327 < 65 years;1291 65-80 years;502 ≥ 80 years) were enrolled.Fever and heart failure were the most common presentations of IE, with no differences among age groups.Patients ≥80 years who underwent surgery were significantly lower compared with other age groups (14.3%,65 years; 20.5%,65-79 years; 31.3%,≥80 years). In-hospital mortality was lower in the <65-year group (20.3%,<65 years;30.1%,65-79 years;34.7%,≥80 years;p < 0.001) as well as 1-year mortality (3.2%, <65 years; 5.5%, 65-80 years;7.6%,≥80 years; p = 0.003).Independent predictors of mortality were age ≥ 80 years (hazard ratio [HR]:2.78;95% confidence interval [CI]:2.32–3.34), CCI ≥ 3 (HR:1.62; 95% CI:1.39–1.88),and non-performed surgery (HR:1.64;95% CI:11.16–1.58).When the three age groups were compared,the AUROC curve for CCI was significantly larger for patients aged <65 years(p < 0.001) for both in-hospital and 1-year mortality. [Conclusion]: There were no differences in the clinical presentation of IE between the groups. Age ≥ 80 years, high comorbidity (measured by CCI),and non-performance of surgery were independent predictors of mortality in patients with IE.CCI could help to identify those patients with IE and surgical indication who present a lower risk of in-hospital and 1-year mortality after surgery, especially in the <65-year group