Publisher Correction: Genetic tool development in marine protists: emerging model organisms for experimental cell biology.

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Genetic tool development in marine protists: emerging model organisms for experimental cell biology.

Diverse microbial ecosystems underpin life in the sea. Among these microbes are many unicellular eukaryotes that span the diversity of the eukaryotic tree of life. However, genetic tractability has been limited to a few species, which do not represent eukaryotic diversity or environmentally relevant taxa. Here, we report on the development of genetic tools in a range of protists primarily from marine environments. We present evidence for foreign DNA delivery and expression in 13 species never before transformed and for advancement of tools for eight other species, as well as potential reasons for why transformation of yet another 17 species tested was not achieved. Our resource in genetic manipulation will provide insights into the ancestral eukaryotic lifeforms, general eukaryote cell biology, protein diversification and the evolution of cellular pathways.

[Neurological complications in critical patients with COVID-19]. / Complicaciones neurológicas en pacientes críticos por SARS-CoV-2.

Introduction: We analysed the neurological complications of patients with severe SARS-CoV-2 infection who required intensive care unit (ICU) admission. Patients and methods: We conducted a retrospective, observational, descriptive study of consecutive patients admitted to the ICU due to severe respiratory symptoms secondary to SARS-CoV-2 infection between 1 April and 1 June 2020. Results: We included 30 patients with neurological symptoms; 21 were men (72.40%), and mean age (standard deviation [SD]) was 57.41 years (11.61). The mean duration of ICU stay was 18.83 days (14.33). The neurological conditions recorded were acute confusional syndrome in 28 patients (93.33%), neuromuscular disease in 15 (50%), headache in 5 (16.66%), cerebrovascular disease in 4 (13.33%), and encephalopathies/encephalitis in 4 (13.33%). CSF analysis results were normal in 6 patients (20%). Brain MRI or head CT showed alterations in 20 patients (66.6%). EEG was performed in all patients (100%), with 8 (26.66%) showing abnormal findings. In 5 of the 15 patients with clinical myopathy, diagnosis was confirmed with electroneuromyography. We found a correlation between older age and duration of ICU stay (P = .002; 95% CI: 4.032-6.022; OR: 3,594). Conclusions: Severe COVID-19 mainly affects men, as observed in other series. Half of our patients presented acute myopathy, and almost all patients left the ICU with acute confusional syndrome, which fully resolved; no correlation was found with EEG or neuroimaging findings. Older age is associated with longer ICU stay.

[Clinical characteristics and complications in patients with OHVIRA (obstructed hemivagina and ipsilateral renal anomaly) syndrome. Our experience]. / Síndrome de OHVIRA: características clínicas y complicaciones, nuestra experiencia.

INTRODUCTION: Obstructed Hemivagina and Ipsilateral Renal Agenesis (OHVIRA) syndrome is a rare variant of Müllerian anomalies. Delay in diagnosis and treatment can produce serious complications in patient's life and fertility. The aim of this study is to present our experience in clinical presentation, diagnosis and complications of patients with OHVIRA syndrome in a 20-year period. PATIENTS AND METHODS: Retrospective analysis of 9 women under 25 years old with OHVIRA syndrome between 1997 and 2017. Analysis included clinical characteristics, demographic, diagnostic methods, follow-up, treatment and complications. RESULTS: A total of 9 patients were studied, 5 diagnosed in prepuberal age and 4 postpuberal. 55% had prenatal diagnosis of renal agenesis and in 3 was incidentally diagnosed. Follow up period for single kidney to diagnosis was 3.6 years (range: 0-13,4 years). Right side was affected in 55%. Symptoms were dysmenorrea (44%), recurrent abdominal pain (22%), urinary dysfunction (22%). Complications were present in postpuberal patients and included hydrometrocolpos (22%) and pyocolpos (11%) requiring septostomy or septum resection. Surgical removal of the septum was performed in 44%). Prepuberal patients were asymptomatic. CONCLUSIONS: OHVIRA syndrome is a rare anomaly in the development of Müllerian ducts with variable clinical presentation. High suspect in patients with single kidney is necessary to avoid potential complications by providing surgical treatment.

INTRODUCCION: El síndrome de OHVIRA (SO) es una rara y compleja variante de las anomalías de los conductos de Müller caracterizado por hemivagina obstruida, útero didelfo y anomalía renal ipsilateral. Su diagnostico prepuberal es raro y el retraso en su diagnóstico y tratamiento compromete la vida y fertilidad de la paciente. MATERIAL Y METODOS: Análisis retrospectivo de las historias clínicas de las pacientes diagnosticadas en nuestro centro en un período de tiempo de 20 años. Los datos se recogen en un protocolo que incluye: características clínicas, diagnóstico, tratamiento y complicaciones. RESULTADOS: Nueve pacientes en total, 55% diagnosticadas en edad prepuberal y 45% postmenarquia. En el 55% se realizó diagnóstico prenatal de malformación renal. En el 33% antecedentes familiares de primer grado de enfermedades nefrourológicas. La media de seguimiento por riñón único, previo al diagnóstico, fue de 3,6 años (rango 0-13,4 años). En el 55% de los casos el lado afecto fue el derecho. Los síntomas fueron ginecológicos en el 44%, miccionales en el 22% y dolor abdominal recurrente en el 22%. Presentaron complicaciones en el 33%, correspondiendo a hidrometrocolpos (22%) y piocolpos (11%). Se realizó septostomía y resección del tabique vaginal como tratamiento en el 44%, todas en edad postpuberal. Las pacientes prepuberales continúan en seguimiento con actitud conservadora y están asintomáticas. CONCLUSIONES: El SO es una rara anomalía del desarrollo de los conductos müllerianos de presentación clínica variable. El alto índice de sospecha y el diagnóstico precoz en niñas con anomalías renales, facilita el tratamiento quirúrgico antes de la presentación de complicaciones.

[Manual detorsion and elective orchiopexy as an alternative treatment for acute testicular torsion in children]. / Detorsión manual y cirugía diferida en la torsión testicular aguda.

AIM: To present our experience in pediatric patients with testicular torsion (TT) treated by manual detorsion (MD). PATIENTS AND METHODS: Retrospective analysis of patients treated by MD in a 10-year period in a single center. Description of symptoms, detorsion technique, follow-up and complications. RESULTS: 76 patients diagnosed with TT were studied in a 10-year period. 16 patients were treated by MD. Mean age was 12 years (Range: 10-13 years) and time from onset of pain was 5.25 hours (±4,2). Left testicle was affected in 75% (n=12). Detorsion maneuver was performed by a pediatric surgeon at the radiology room, in counter-clockwise direction in the right testicle and clockwise direction in the left testicle in all cases. The success was defined as the relief of pain, normal physical examination and was confirmed by Doppler ultrasound performed immediately after MD. MD was effective in 75% (n=12) and orchiopexy was performed under elective conditions at median time of 2 weeks (0-5 weeks). MD was unsuccessful in 3 patients and emergency orchiopexy was performed with no testicular loss. 1 patient had a second MD maneuver for incomplete detorsion. No short or long term complication nor testicular atrophy was observed. CONCLUSION: MD and elective orchiopexy seems to be an efficient and reliable procedure in the treatment of TT in children. Further studies may be necessary to establish its safety and indications.

OBJETIVO: Presentar nuestra experiencia, protocolo e indicaciones de la detorsión testicular manual (DM) como tratamiento en la torsión testicular (TT). MATERIAL Y METODOS: Estudio retrospectivo de pacientes con TT tratados mediante DM en los últimos 10 años. Analizamos tiempo de evolución, técnica de detorsión, evolución y complicaciones. RESULTADOS: 76 pacientes diagnosticados de TT en los últimos 10 años, de los cuales 21% (n=16) fueron tratados mediante DM. Edad media de 12 años (rango: 10-13 años) y duración del comienzo del dolor de 5,25 horas (± 4,2 horas), mayor frecuencia en el testículo izquierdo (75%, n=12). La técnica de DM se realizó ecoguiada, en dirección horaria y antihoraria en el lado derecho e izquierdo, respectivamente. El éxito se definió como el alivio inmediato de los síntomas, hallazgos normales en el examen físico y comprobación de la recuperación del flujo mediante ecografía tras la maniobra de detorsión. Fue efectiva en el 75% (n=12), siendo dados de alta a las 24 horas, tras realizar nueva ecografía de control y comprobar normalidad en el flujo. Orquidopexia vía escrotal diferida a las 2 semanas (rango: 0-5,4 semanas). En tres pacientes (18,8%) se realizó cirugía urgente por insuficiente recuperación del flujo y en otro paciente (6,2%) fue necesario realizar una segunda maniobra de detorsión. No hubo complicaciones tras DM a corto/largo plazo, ningún caso de atrofia testicular. CONCLUSIONES: La DM ecoguiada y orquidopexia diferida es una opción terapéutica en pacientes con TT de corta evolución. Es necesario series más amplias y realizar estudios prospectivos para establecer su seguridad y eficacia.

Direct-location versus verbal report methods for measuring auditory distance perception in the far field.

In this study we evaluated whether a method of direct location is an appropriate response method for measuring auditory distance perception of far-field sound sources. We designed an experimental set-up that allows participants to indicate the distance at which they perceive the sound source by moving a visual marker. We termed this method Cross-Modal Direct Location (CMDL) since the response procedure involves the visual modality while the stimulus is presented through the auditory modality. Three experiments were conducted with sound sources located from 1 to 6 m. The first one compared the perceived distances obtained using either the CMDL device or verbal report (VR), which is the response method more frequently used for reporting auditory distance in the far field, and found differences on response compression and bias. In Experiment 2, participants reported visual distance estimates to the visual marker that were found highly accurate. Then, we asked the same group of participants to report VR estimates of auditory distance and found that the spatial visual information, obtained from the previous task, did not influence their reports. Finally, Experiment 3 compared the same responses that Experiment 1 but interleaving the methods, showing a weak, but complex, mutual influence. However, the estimates obtained with each method remained statistically different. Our results show that the auditory distance psychophysical functions obtained with the CMDL method are less susceptible to previously reported underestimation for distances over 2 m.

[Retrospective analysis of morbidity and mortality of intestinal atresias in newborns]. / Análisis retrospectivo de la morbilidad y mortalidad de las atresias intestinales diagnosticadas en el periodo neonatal.

OBJECTIVE: Intestinal atresia (IA) is the most common obstructive congenital malformation in the gastrointestinal tract. The aim is to describe the morbidity and mortality of AI in our series. METHODS: Retrospective study in infants with AI who underwent surgery in our hospital in the past 15 years. Descriptive analysis was performed by collecting clinical and epidemiological variables. Qualitative and quantitative statistical analysis were performed. RESULTS: A total of 32 patients, 40.6% (13) women and 59.4% (19) males, maternal age 31 ± 5 years. Prenatal care in 96.8% (30) and prenatal diagnosis in 68.8% (22). Gestational age 35 ± 3 (SG 25-41), birth weight 2,506 ± 516 g (920-3,470 g). 53% (17/32) were localized in duodenum (65% extrinsic, 35% type I); 37.5% (12/32) jejunoileal (16.6% type I, 25% type II, 16.6% type IIIa, 16.6% type IIIb and 25% type IV); 6.5% (2/32) were colonic and 3% (1/32) pyloric. In 65.6% (21/32) it was associated with other congenital malformation. 81.3% (26) were operated within the first 48 hours of life. 15.6% (5/32) required enterostomy. 21.8% (7/32) had complications requiring reoperation in 71% (5/7) with 1 case of short bowel syndrome. Median time to enteral nutrition onset was 10 days (IQR 7-15), higher in patients with ileal atresia. Hospital stay was 33 days (interquartile range 23-66 days) and overall mortality of 9.3%. CONCLUSION: In our series the congenital malformations associated with intestinal atresia were determinant in the prognosis and mortality of these patients.

OBJETIVOS: La atresia intestinal es la malformación congénita obstructiva del tubo digestivo más frecuente. Nuestro objetivo es describir la morbilidad y mortalidad de las atresias intestinales en nuestro medio. MATERIAL Y METODOS: Estudio retrospectivo de neonatos con atresia intestinal intervenidos en nuestro centro en los últimos 15 años. Se realiza un análisis descriptivo de variables clínicas y epidemiológicas. RESULTADOS: Un total de 32 pacientes, 40,6% (13) mujeres y 59,4% (19) varones, edad materna de 31 ± 5 años, controles prenatales en el 96,8% (30) y diagnóstico prenatal en 68,8% (22). Edad gestacional de 35 ± 3 (25-41 SG), peso al nacer 2.506 ± 516 g (920-3.470 g). El 53% (17/32) de localización duodenal (65% extrínseca y 35% tipo I); el 37,5% (12/32) yeyunoileal (16,6% tipo I, 25% tipo II, 16,6% tipo IIIa, 16,6% tipo IIIb y 25% tipo IV); el 6,5% (2/32) colónica y 3% (1/32) pilórica. El 65,6% (21/32) asociaba otra malformación congénita. El 81,3% (26) fueron intervenidos en las primeras 48 horas de vida, precisando derivación intestinal un 15,6% (5/32). El 21,8% (7/32) presentaron complicaciones, de los cuales el 71% (5/7) requirieron reintervención, con un caso de intestino corto. El tiempo medio de inicio de nutrición enteral fue 10 días (RIQ 7-15), mayor en los pacientes con atresia ileal; la estancia hospitalaria fue de 33 días (RIQ 23-66 días) y la mortalidad general, del 9,3%. CONCLUSIONES: Las malformaciones congénitas asociadas en pacientes con atresia intestinal son un factor determinante en el pronóstico y mortalidad de los mismos.

[Management and description of neonatal tumours in a surgical oncology unit]. / Tumores neonatales: experiencia en una Unidad de Cirugía Oncológica.

AIM: Neonatal tumours represents less than 2% of all childhood cancers. The biological behaviour of this tumours will differ in older children. The tumours's biological differences and the immature physiological characteristics of newborns represent a great therapeutically challenge making newborns vulnerable. The aim of this study is to describe the clinical characteristics, associated malformations, diagnostic methods, treatment and the outcomes of neonatal tumours. METHODS: Retrospective review of patients ≤ 28 days-old with diagnosis of neonatal tumour between 2000-2016. Statistical analysis of clinical characteristics, histology, diagnostic methods, treatment and morbimortality. RESULTS: A total of 26 tumours were diagnosed in newborns with a mean age of 4.85 ± 8.9 days and 69.2% of boys. Prenatal diagnosis was achieved in 38.5% (n = 10) and 38.5% (n = 10) in the first week of age. Associated malformations were found in 30.6% (n = 8). The most frequent tumours were hepatic hemangioma 23.1% (n = 6), neuroblastoma 15.4% (n = 4) and sacrococcygeal teratoma 11.5% (n = 3). Medical treatment was indicated in 7.7% (n = 5), surgical 57.7% (n = 15) and observation 30.8% (n = 7). Global mortality was 19.23% (n = 5) of which 42.9% (n = 3/7) were perioperatively. CONCLUSIONS: The management of neonatal tumours require a multidisciplinary approach to minimize the consequences and assure the best outcome. Global mortality is low and depends primarily of the physiologic and association of other malformations of the newborn.

OBJETIVO: Los tumores neonatales representan menos del 2% de los tumores pediátricos, sin embargo, el comportamiento biológico difiere de los desarrollados en otros grupos de edad. Estas características, junto a la inmadurez neonatal, dificultan el tratamiento, convirtiéndolos en un grupo muy vulnerable. El objetivo de este estudio es describir las características clínicas, anomalías asociadas, diagnóstico y repercusión del tratamiento de los tumores neonatales. MATERIAL: Estudio retrospectivo de pacientes ≤ 28 días diagnosticados de tumor neonatal entre 2000-2016. Se realizó análisis estadístico de las principales características clínicas, histológicas, métodos diagnósticos, tratamientos establecidos y morbimortalidad. RESULTADOS: Se diagnosticaron 26 recién nacidos con tumores. El 69,2% varones, con edad media al diagnóstico de 4,85 ± 8,9 días. El diagnóstico fue prenatal en 38,5% (n = 10) y 38,5% (n = 10) en la primera semana de vida. El 30,6% (n = 8) asoció otra malformación. Los tumores más frecuentes fueron los hemangiomas hepáticos, 23,1% (n = 6), neuroblastoma, 15,4% (n = 4) y teratoma sacrococcígeo, 11,5% (n = 3). Se realizó tratamiento médico en 7,7% (n = 5), quirúrgico en 57,7% (n = 15) y conservador en 30,8% (n = 7). La mortalidad global fue del 19,23% (n = 5), de los cuales 42,9% (n = 3/7) casos ocurrieron durante el periodo perioperatorio. CONCLUSIONES: El manejo de los tumores neonatales requiere un equipo multidisciplinar para minimizar las secuelas y garantizar el mejor resultado. El manejo conservador es una opción terapéutica válida en determinados tipos de tumores. La mortalidad global es baja y depende principalmente de las características fisiológicas del neonato y de sus malformaciones asociadas.

[Peritoneal drainage as definitive treatment in necrotizing enterocolitis of preterm infants with low weight]. / Drenaje peritoneal como tratamiento definitivo en la enterocolitis necrotizante de prematuros de bajo peso.

OBJECTIVES: The management of advanced necrotizing enterocolitis (NEC) in preterm birth with low weight remains controversial. The aim of this study consists in the analysis of the results of treatment in these patients, as well as the evaluation of the role of peritoneal drainage as a definitive therapeutic option. METHODS: Observational and descriptive study of 31 patients under 1,500 g of weight with advanced NEC, whom have had surgery in our center in the last 15 years. They were classified in two groups: G1 (n = 21) <1,000 g and G2 (n = 10) 1,000-1,500 g. RESULTS: Average weight in G1 patients was 791.7 ± 137.5 g and 1,280.7 ± 207.9 g in G2 patients (p <0.01). Average gestational age was 26 ± 1 weeks in G1 patients and 30 ± 2 weeks in G2 patients (p <0.01). Mean time to the start of the advanced NEC was 9,4 ± 4.4 days in G1 patients and 16.7 ± 13.5 days in G2 patients (p = 0.031). In group G1, 95.2% of the patients were treated throughout peritoneal drainage, and 4,8% (n = 1) with laparotomy. In G2, 60% (n = 6) of the patients were treated throughout peritoneal drainage, and 40% (n = 4) with laparotomy (p = 0.027). The peritoneal drainage was a definitive treatment in 84.2% (16/20) of the G1 patients, with a survival rate of 56.3% (n = 9); G2 patients had a definitive treatment in 50% of the patients (3/6), with a survival rate of 66.7% (n = 2) (p = 0.261). In G1 patients, 50% (2/4) of the drains which required subsequently laparotomy, died 0% (0/3) in G2 patients. CONCLUSIONS: Peritoneal drainage is primarily a valid therapeutic option in extremely premature infants and can be used as definitive treatment.

OBJETIVO: El manejo de la enterocolitis necrotizante (ECN) avanzada en prematuros de bajo peso continúa siendo controvertido. El objetivo de este estudio es analizar los resultados del tratamiento en estos pacientes, así como valorar el papel del drenaje peritoneal como opción terapéutica definitiva. MATERIAL Y METODOS: Estudio observacional y descriptivo de 31 pacientes menores de 1.500 g de peso, intervenidos en nuestro centro, con ECN avanzada en los últimos 15 años. Se clasificaron en dos grupos en función del peso: G1 <1.000 g (n = 21) y G2 1.000-1.500 g (n = 10). RESULTADOS: El peso medio en los pacientes del G1 fue de 791,7 ± 137,5 g y de 1.280,7 ± 207,9 g en el G2 (p <0,01). La edad gestacional media de 26 ± 1 semanas en el G1 y de 30 ± 2 semanas en el G2 (p <0,01). El tiempo medio hasta el comienzo del cuadro de ECN avanzada fue de 9,4 ± 4,4 días en el G1 y de 16,7 ± 13,5 días en el G2 (p = 0,031). En el G1 el 95,2% (n = 20) de los pacientes se trataron mediante drenaje peritoneal y el 4,8% (n = 1) mediante laparotomía; en el G2 el 60% (n = 6) se trataron con drenaje peritoneal y el 40% (n = 4) mediante laparotomía (p = 0,027). El drenaje peritoneal fue el tratamiento definitivo en el 84,2% (16/20) del G1, con una supervivencia del 56,3% (n = 9); en el G2 el 50% (3/6), con una supervivencia del 66,7% (n = 2) (p = 0,261). En el G1 fallecieron el 50% (2/4) de pacientes que tras el drenaje precisaron posteriormente laparotomía, mientras que en el G2 no falleció ningún paciente (0/3). CONCLUSION: El drenaje peritoneal es una opción terapéutica válida fundamentalmente en prematuros extremos y puede ser empleado como tratamiento definitivo.

Hepatitis C virus genotype 4: Genotype 1's little brother.

Treatment for hepatitis C virus genotype 4 infection has undergone a major advance over the past 5 years with the emergence of direct-acting antiviral agents. Previously, genotype 4 treatment had been limited to the combination of pegylated interferon and ribavirin, with low rates of sustained virological response. The combinations of new direct-acting agents have resulted in a radical improvement in hepatitis C therapy. Much of the currently available efficacy and safety information in the treatment of genotype 4 has been extrapolated through the results of genotype 1. In this report, we review the efficacy and safety data obtained in recent studies focusing on genotype 4 patients, including special populations, such as those with decompensated cirrhosis.

Cost-effectiveness analysis of ledipasvir/sofosbuvir in patients with chronic hepatitis C: Treatment of patients with absence or mild fibrosis compared to patients with advanced fibrosis.

To evaluate the cost-effectiveness of ledipasvir/sofosbuvir (LDV/SOF) in treatment-naïve patients with chronic hepatitis C (CHC) genotype 1 (GT1) in the absence or mild fibrosis (F0-F1) versus advanced fibrosis (F2-F4), from the perspective of the Spanish Health System. A Markov model was developed to simulate disease progression, estimating costs and outcomes [life years gained (LYG) and quality-adjusted life years (QALY)] derived from starting with LDV/SOF in patients with F0-F1 compared with F2-F4. Therapy duration was 8 weeks in noncirrhotic patients with viral load <6 million IU/mL and 12 weeks in the remaining patients. Sustained virologic response rates were obtained from real-world cohort studies. Transition probabilities, utilities and direct costs were obtained from the literature. A 3% annual discount rate was applied to costs and outcomes. Sensitivity analyses were performed. LDV/SOF in F0-F1 patients was a dominant strategy, being more effective (19.85 LYG and 19.80 QALY) than beginning treatment in F2-F4 patients (18.63 LYG and 16.25 QALY), generating savings of €9228 per patient (€3661 due to disease management and monitoring). In a cohort of 1000 patients, LDV/SOF in F0-F1 patients decreased the number of cases of decompensated cirrhosis (93%), hepatocellular carcinoma (97%) and liver-related deaths (95%) and prevented 6 liver transplants compared to initiating LDV/SOF in F2-F4 patients. In CHC treatment-naïve GT1 patients, starting treatment with LDV/SOF in patients with F0-F1 compared to those with F2-F4 increases effectiveness by 1.22 LYG and 3.55 QALY gained and reduces disease burden and it is associated with cost savings.

Interferon-free therapies for patients with chronic hepatitis C genotype 3 infection: A systematic review.

Treatment of hepatitis C virus (HCV) infection with genotype 3 remains a challenge. The HCV elimination rate with direct-acting antivirals (DAAs) is lower than the values reported for other HCV genotypes. In addition, genotype 3-infected patients have a higher risk of disease progression and hepatocellular carcinoma. The aim of this study was to review the relevant literature concerning the treatment of HCV genotype 3 patients with interferon-free regimens. A literature search was conducted in the PubMed/Medline, Embase and Web of Science electronic databases. Trials enrolling patients with chronic hepatitis C infection treated with DAAs with or without ribavirin were included. Two investigators independently evaluated the trials for inclusion criteria, risk of bias and data extraction. The primary outcome was sustained virological response (SVR). In total, 323 references were identified, and 29 met the inclusion criteria: 18 general clinical trials, three general observational studies, three studies in patients with decompensated liver cirrhosis and four studies in HIV-HCV-coinfected patients. Overall, 4068 genotype 3 patients were included. As compared with sofosbuvir and ribavirin for 24 weeks, sofosbuvir/velpatasvir for 12 weeks or sofosbuvir plus daclatasvir plus ribavirin for 12 weeks provided higher SVR rates, particularly in patients with cirrhosis. Treatment of patients with decompensated cirrhosis remains a great challenge. Sofosbuvir/ledipasvir+ribavirin for 12 weeks were associated with an SVR of 85% in these patients. In summary, treatment of HCV genotype 3 patients is improving rapidly, and this population may no longer be considered a difficult-to-treat subgroup in the near future.

Effectiveness and safety of sofosbuvir-based regimens plus an NS5A inhibitor for patients with HCV genotype 3 infection and cirrhosis. Results of a multicenter real-life cohort.

Patients with HCV genotype 3 (GT3) infection and cirrhosis are currently the most difficult to cure. We report our experience with sofosbuvir+daclatasvir (SOF+DCV) or sofosbuvir/ledipasvir (SOF/LDV), with or without ribavirin (RBV) in clinical practice in this population. This was a multicenter observational study including cirrhotic patients infected by HCV GT3, treated with sofosbuvir plus an NS5A inhibitor (May 2014-October 2015). In total, 208 patients were included: 98 (47%) treatment-experienced, 42 (20%) decompensated and 55 (27%) MELD score >10. In 131 (63%), treatment was SOF+DCV and in 77 (37%), SOF/LDV. Overall, 86% received RBV. RBV addition and extension to 24 weeks was higher in the SOF/LDV group (95% vs 80%, P=.002 and 83% vs 72%, P=.044, respectively). A higher percentage of decompensated patients were treated with DCV than LDV (25% vs 12%, P=.013). Overall, SVR12 was 93.8% (195/208): 94% with SOF+DCV and 93.5% with SOF/LDV. SVR12 was achieved in 90.5% of decompensated patients. Eleven treatment failures: 10 relapses and one breakthrough. RBV addition did not improve SVR (RR: 1.08; P=.919). The single factor associated with failure to achieve SVR was platelet count <75×10E9/mL (RR: 3.50, P=.019). In patients with MELD <10, type of NS5A inhibitor did not impact on SVR12 (94% vs 97%; adjusted RR: 0.49). Thirteen patients (6.3%) had serious adverse events, including three deaths (1.4%) and one therapy discontinuation (0.5%), higher in decompensated patients (16.7% vs 3.6%, P<.006). In patients with GT3 infection and cirrhosis, SVR12 rates were high with both SOF+DCV and SOF/LDV, with few serious adverse events.

Ultrafine particles and black carbon personal exposures in asthmatic and non-asthmatic children at school age.

Traffic-related air pollution (TRAP) exposure during childhood is associated with asthma; however, the contribution of the different TRAP pollutants in each microenvironment (home, school, transportation, others) in asthmatic and non-asthmatic children is unknown. Daily (24-h) personal black carbon (BC), ultrafine particle (UFP), and alveolar lung-deposited surface area (LDSA) individual exposure measurements were obtained from 100 children (29 past and 21 current asthmatics, 50 non-asthmatics) aged 9±0.7 years from the INMA-Sabadell cohort (Catalonia, Spain). Time spent in each microenvironment was derived by the geolocation provided by the smartphone and a new spatiotemporal map-matching algorithm. Asthmatics and non-asthmatics spent the same amount of time at home (60% and 61%, respectively), at school (20% and 23%), on transportation (8% and 7%), and in other microenvironments (7% and 5%). The highest concentrations of all TRAPs were attributed to transportation. No differences in TRAP concentrations were found overall or by type of microenvironment between asthmatics and non-asthmatics, nor when considering past and current asthmatics, separately. In conclusion, asthmatic and non-asthmatic children had a similar time-activity pattern and similar average exposures to BC, UFP, and LDSA concentrations. This suggests that interventions should be tailored to general population, rather than to subgroups defined by disease.

[Correlation between prenatal ultrasound and postnatal diagnosis of birth defects]. / Correlación entre la ecografía prenatal y el diagnóstico postnatal de las malformaciones congénitas.

OBJECTIVES: To assess the accuracy of prenatal ultrasound diagnosis and to analyze the protocol applied for congenital defects (CD) in our environment. METHODS: Descriptive study of prenatally diagnosed CD in our area between 2004-2013. Includes: total births, fetal medicine referrals (number of consultations, ultrasound, invasive techniques) anatomical and chromosomal abnormalities, confirmed diagnoses, necropsies performed, false diagnoses, absence of prenatal diagnoses, and number and reasons for abortions (VIEs). RESULTS: Mean annual births were 3,646 ± 1,299, with a mean prenatal ultrasound of 2,144 ± 307 and 512 ± 74 invasive techniques per year. The annual average of prenatal chromosomopathies diagnosed were 26 ± 8 and 140 ± 14 anatomical abnormalities, which represents a 36.44% from all of the prenatal ultrasound performed. These include: neurological, cardiac and nephron-urological anatomic anomalies. Pre and post-natal correlation was observed in 95.6% of the DCs detected. Most common causes of abortion were chromosomal abnormalities, heart and neurological diseases. CONCLUSIONS: Due to the variety of CD that cause VIEs, a highly specialized multidisciplinary approach is recommended to ensure optimal information for parents.

OBJETIVOS: Valorar la precisión del diagnóstico ecográfico prenatal y analizar el protocolo de actuación frente a un determinado defecto congénito (DC) en nuestro medio. MATERIAL Y METODOS: Estudio descriptivo de los DC diagnosticados prenatalmente en nuestra área sanitaria entre los años 2004-2013. Como variables del estudio se incluyeron el número de nacimientos totales, derivaciones a medicina fetal (número de consultas, ecografías, técnicas invasivas) anomalías anatómicas por sistemas, cromosomopatías, diagnósticos confirmados, necropsias realizadas, falsos diagnósticos, ausencia de diagnóstico prenatal, número y motivo de interrupciones voluntarias del embarazo (IVEs). RESULTADOS: Durante el período estudiado, la media de nacimientos anuales fue de 3.646 ± 1.299, con una media de 2.144 ± 307 ecografías prenatales y 512 ± 74 técnicas invasivas anuales. La media anual de diagnóstico prenatal fue de 26 ± 8 cromosomopatías y 140 ± 14 anomalías anatómicas que suponen un 36,44% del total de las ecografías prenatales realizadas. Entre estas últimas se observaron malformaciones del sistema urinario, cardíacas y neurológicas, entre otras. Se observó correlación pre y postnatal en el 95,6% de los DC detectados. Las causas de interrupción del embarazo más frecuentes fueron las cromosomopatías, seguidas de las malformaciones congénitas (MC) cardíacas y neurológicas. CONCLUSIONES: Debido a la variedad de DC que originan IVE, es recomendable un abordaje multidisciplinar altamente especializado que garantice una información óptima a los padres.

[Clinical and immunohistochemical correlation of balanitis xerotica obliterans]. / Correlación clínica e inmunohistoquímica de la balanitis xerotica obliterans.

AIM: Balanitis xerotica obliterans (BXO) is a disease of the skin and mucosa of male genitals of unknown etiology that may affect children of any age. It has a low incidence (9-19%) and in adults is considered a potential premalignant lesion. The aim of our study is to establish the incidence of BXO in our center and to determine its correlation between the clinical and immunohistochemical (IHC) findings. METHODS: Prospective cohort including all children < 14 years with foreskin pathology that required a circumcision between 2014-2016. Statistical analysis of the clinical characteristics, histological and IHC findings searching for inflammatory response, premalignant lesions and microbiological findings. RESULTS: A total of 176 boys with phimosis had circumcision with a mean age of 7 ± 3 years (Range 2-14). Presurgical diagnosis of BXO was suspected in 28.4% (n= 50) whereas the AP confirmed a total of 29.5% (n= 53) with a very good interobserver concordance (kappa= 0.81: p< 0.01). Previous treatment with corticoids in BXO was found in 63.5% (n= 33/52). Meatal stenosis was found in 7.69% (n= 4/52) requiring meatal/urethral dilations. Patients with BXO had a T-Lymphocytes CD3+ mediated inflammatory response with a positive correlation between tumor suppressing protein (p53) expression and chronic inflammation. CONCLUSIONS: BXO is a chronic inflammatory disease mediated by T-lymphocytes with an incidence greater than previously reported. Surgeons' criterion has a very good concordance with the AP findings. The elevation of p53 in children with BXO may indicate a plausible malignant potential that may require a surgical treatment (circumcision) and an adequate follow-up.

OBJETIVO: La balanitis xerotica obliterans (BXO) es una enfermedad de etiología incierta, que afecta a piel y mucosa de genitales masculinos de cualquier edad. La incidencia en niños es baja (9-19%) y en adultos se considera una lesión premaligna. El objetivo de este estudio es establecer la incidencia de BXO en nuestro centro y determinar la correlación entre las características clínicas y los hallazgos inmunohistoquímicos (IHQ). METODOS: Cohorte prospectiva de niños ≤14 años con fimosis circuncidados entre 2014-2016. Análisis estadístico de las características clínicas e histológicas e IHQ para valorar la respuesta inflamatoria, presencia de lesiones premalignas y asociaciones microbiológicas. RESULTADOS: Se incluyeron 176 pacientes circuncidados con una edad media de 7 ± 3 años (rango 2-14 años). La sospecha clínica de BXO, 28,4% (n= 50), se confirmó mediante anatomía patológica en 29,5% (n= 52) con muy buena fuerza de concordancia interobservador (kappa= 0,81: p< 0,01). El 63,5% (n= 33/52) recibieron corticoterapia como tratamiento inicial. El 7,69% (4/52) presentaron estenosis meatal requiriendo dilataciones meatales/uretrales. Los casos de BXO presentaron una respuesta mediada por linfocitos-T: CD3+ (p< 0,01) y correlación positiva con la sobreexpresión de proteína supresora de tumores (p53) (p< 0,01). CONCLUSIONES: BXO es una enfermedad inflamatoria crónica mediada por linfocitos-T con una incidencia mayor a la reportada. La concordancia interobservador entre la sospecha de BXO y la confirmación histológica es muy buena. La elevación de p53 en los pacientes con BXO indica un posible potencial maligno que requiere tratamiento quirúrgico (circuncisión) y un seguimiento adecuado.

Removal from liver transplantation list of a hepatitis C virus-HIV co-infected patient after successful treatment with sofosbuvir and daclatasvir.

We present a human immunodeficiency virus-infected patient with severe decompensated hepatitis C virus-related cirrhosis awaiting liver transplantation (LT) who received a 24-week course of interferon/ribavirin-free antiviral treatment with sofosbuvir and daclatasvir on a compassionate basis. Rapid viral suppression was associated with progressive improvement of his liver function tests. The patient achieved a sustained virological response and concomitant clinical improvement, which prompted removal from the LT list 12 weeks after the end of treatment.

Conservation Status of Long-Finned Pilot Whales, Globicephala melas, in the Mediterranean Sea.

Mediterranean Sea long-finned pilot whales (Globicephala melas) are currently classified as Data Deficient on the International Union for the Conservation of Nature (IUCN) Red List. Multiple lines of evidence, including molecular genetic and photo-identification mark-recapture analyses, indicate that the Strait of Gibraltar population (distributed from 5.8°W longitude to west of Djibouti Bank and Alborán Dorsal in the Alborán Sea) is differentiated from the Mediterranean Sea population (east of Djibouti Bank and the Alborán Dorsal up to the Ligurian Sea). There is low genetic diversity within the Mediterranean population, and recent gene flow with the Strait of Gibraltar population is restricted. Current total abundance estimates are lacking for the species in the Mediterranean. Pilot whales in the Alborán Sea region were negatively affected by a morbillivirus epizootic from 2006 to 2007, and recovery may be difficult. The Strait of Gibraltar population, currently estimated to be fewer than 250 individuals, decreased by 26.2% over 5 years after the morbillivirus epizootic. Population viability analyses predicted an 85% probability of extinction for this population over the next 100 years. Increasing maritime traffic, increased contaminant burdens, and occasional fisheries interactions may severely impair the capacity of the Strait of Gibraltar population to recover after the decline due to the pathogen.

Conservation Status of Killer Whales, Orcinus orca, in the Strait of Gibraltar.

Killer whales (Orcinus orca) in the Mediterranean Sea are currently restricted to the Strait of Gibraltar and surrounding waters. Thirty-nine individuals were present in 2011, with a well-differentiated social structure, organized into five pods. Killer whale occurrence in the Strait is apparently related to the migration of their main prey, Atlantic bluefin tuna (Thunnus thynnus). In spring, whale distribution was restricted to shallow waters off the western coast of the Strait where all pods were observed actively hunting tuna. In summer, the whales were observed in the shallow central waters of the Strait. A relatively new feeding strategy has been observed among two of the five pods. These two pods interact with an artisanal drop-line fishery. Pods depredating the fishery had access to larger tuna in comparison with pods that were actively hunting. The Strait of Gibraltar killer whales are socially and ecologically different from individuals in the Canary Islands. Molecular genetic research has indicated that there is little or no female-mediated gene migration between these areas. Conservation threats include small population size, prey depletion, vessel traffic, and contaminants. We propose the declaration of the Strait of Gibraltar killer whales as an endangered subpopulation. A conservation plan to protect the Strait of Gibraltar killer whales is urgently needed, and we recommend implementation of a seasonal management area where activities producing underwater noise are restricted, and the promotion of bluefin tuna conservation.

Beat-to-beat electrocardiographic analysis of ventricular repolarization variability in patients after myocardial infarction.

Several studies have shown that the beat-to-beat variability of ventricular repolarization, which can be computed by T-wave spectral variance (TSV) index, constitutes a marker of cardiac risk. Moreover, the fact that properties of action potential duration are altered during the healing (days, weeks) and healed (months) infarct stages, have been reported. However, no data exist regarding the influence of the time elapsed after myocardial infarction (MI) on modulation of the beat-to-beat ventricular repolarization variability. In the present work we have evaluated TSV index during healing and healed stages of MI using 12 standard ECG leads. The ECG of control or healthy subjects (n = 49) and the ECGs in patients after MI (n = 38), one within the first seven days (MI7) and the other after 60 days (MI60) of cardiac infarction, have been analyzed. We have considered the preferential ECG leads as those leads in which TSV index have presented a relative change greater than 10 in MI7 respect to control. Results indicate that TSV index have shown a significant increase (p < 0.0005) in I, II, aVR, aVF, V3, V4, V5 and V6 leads in healing phase of MI (MI7) with respect to control. Further, in the healed phase of MI (MI60), the TSV index tends to decrease their values towards the control. Also, we have computed a multilead TSV index based on the preferential ECG leads. In that sense, the multilead criteria have shown better perfomance quantifying beat-to-beat repolarization variability than any single ECG lead considered. The sensitivity, specificity and AUC of TSV index were: 92%, 90% and 0.96 for MI7; and 76%, 84% and 0.81 for MI60, respectively. Moreover, the beat-to-beat ventricular repolarization variability has been quantified by the QT variability index (QTVI). Even though the results that we have obtained with TSV index have been comparable to those obtained with the QTVI, this latter has not reflected the modulation effect associated to time elapsed after MI. Also, the preferential ECG leads depending on MI site using TSV index have been computed, being lead V4 for anterior and lead aVF for inferior MI, respectively. Finally, this study might help understand the role of healing and healed stages following MI on beat-to-beat variability modulation of ventricular repolarization.