Botrytis cinerea combines four molecular strategies to tolerate membrane-permeating plant compounds and to increase virulence.

Saponins are plant secondary metabolites comprising glycosylated triterpenoids, steroids or steroidal alkaloids with a broad spectrum of toxicity to microbial pathogens and pest organisms that contribute to basal plant defense to biotic attack. Secretion of glycosyl hydrolases that enzymatically convert saponins into less toxic products was thus far the only mechanism reported to enable fungal pathogens to colonize their saponin-containing host plant(s). We studied the mechanisms that the fungus Botrytis cinerea utilizes to be tolerant to well-characterized, structurally related saponins from tomato and Digitalis purpurea. By gene expression studies, comparative genomics, enzyme assays and testing a large panel of fungal (knockout and complemented) mutants, we unraveled four distinct cellular mechanisms that participate in the mitigation of the toxic activity of these saponins and in virulence on saponin-producing host plants. The enzymatic deglycosylation that we identified is novel and unique to this fungus-saponin combination. The other three tolerance mechanisms operate in the fungal membrane and are mediated by protein families that are widely distributed in the fungal kingdom. We present a spatial and temporal model on how these mechanisms jointly confer tolerance to saponins and discuss the repercussions of these findings for other plant pathogenic fungi, as well as human pathogens.

[Knowledge of chronic venous disease among healthcare professionals in Spain]. / Conocimiento de la enfermedad venosa crónica en los profesionales sanitarios en España.

INTRODUCTION: Chronic venous disease (CVD) is classified as the most prevalent vascular disease in humans. It has been associated with an increased incidence of cardiovascular diseases and is a strong predictor of all-cause mortality, representing a public health problem of the first magnitude. The objective of this study was to analyze the actions in the management of CVD in the daily clinical practice of health professionals in Spain. MATERIAL AND METHODS: Observational, descriptive and cross-sectional study with data collection through an opinion survey of 22 questions completed electronically through a Google® form for professionals involved in chronic venous disease care. Three hundred surveys were analyzed. The quantitative variables were represented with means and standard deviation and the qualitative ones with percentages and confidence intervals. RESULTS: Three hundred surveys analyzed. 65.3% were women. The most participatory age group was over 55 years of age. 85% of those surveyed considered that CVD is an underdiagnosed and undertreated disease, with an added negative impact in terms of follow-up during the Covid-19 pandemic, since 91.7% considered that it had not been adequate. 47% of the participants did not know the CEAP classification and 56.3% did not know the venous clinical severity scale (VCSS). 92.7% of physicians prescribed compression stockings and 74.7% phlebotonic drugs. Hidrosmine was the best known and most prescribed venoactive drug (51.7%). 73% of the doctors recognized that they did not use any algorithm or protocol for the diagnosis, treatment and monitoring of CVD in their usual clinical practice and 91% stated that they were not trained in their workplaces. 54.3% of the physicians believed that one of the main limitations that made follow-up of the disease difficult was the lack of coordination with the vascular surgeons. CONCLUSIONS: Updating and responding to the training needs of professionals regarding CVD is essential to guarantee quality care continuity in the care of our patients.

Quality of life with first-line pembrolizumab for PD-L1-positive advanced gastric/gastroesophageal junction adenocarcinoma: results from the randomised phase III KEYNOTE-062 study.

BACKGROUND: In the randomised phase III KEYNOTE-062 study, pembrolizumab was non-inferior to chemotherapy for overall survival in patients with programmed death-ligand 1 (PD-L1)-positive [combined positive score (CPS) ≥1] advanced gastric/gastroesophageal junction (GEJ) cancer. We present findings of prespecified health-related quality-of-life (HRQOL) analyses for pembrolizumab versus chemotherapy in this population. MATERIALS AND METHODS: HRQOL, a secondary endpoint, was measured in patients who received ≥1 dose of study treatment and completed ≥1 HRQOL questionnaire [European Organisation for the Research and Treatment of Cancer (EORTC) 30-question quality-of-life (QLQ-C30), EORTC 22-question quality-of-life gastric-cancer-specific module (QLQ-STO22)]. Least squares mean (LSM) change (baseline to week 18) in global health status/quality of life (GHS/QOL; EORTC QLQ-C30) and time to deterioration (TTD) in GHS/QOL, nausea/vomiting and appetite loss scores (EORTC QLQ-C30) and abdominal pain/discomfort scores (EORTC QLQ-STO22) were evaluated. RESULTS: The HRQOL population comprised 495 patients with CPS ≥1 (pembrolizumab, 252; chemotherapy, 243). Compliance rates at week 18 were similar for pembrolizumab and chemotherapy (EORTC QLQ-C30, 87.9% and 81.9%; EORTC QLQ-STO22, 87.9% and 81.3%, respectively). There was no between-arm difference in LSM score change in GHS/QOL [-0.16; 95% confidence interval (CI) -5.01 to 4.69; P = 0.948]. The LSM score change for most subscales showed comparable worsening in both arms. TTD for GHS/QOL [hazard ratio (HR), 0.96; 95% CI, 0.67-1.38; P = 0.826], appetite loss (HR, 0.83; 95% CI, 0.58-1.20; P = 0.314) and pain (HR, 1.22; 95% CI, 0.78-1.91; P = 0.381) were similar between arms. Longer TTD was observed for pembrolizumab versus chemotherapy for nausea/vomiting (HR, 0.61; 95% CI, 0.44-0.85; P = 0.003). CONCLUSIONS: HRQOL was maintained with first-line treatment with pembrolizumab in patients with PD-L1-positive advanced gastric/GEJ cancer and was similar between pembrolizumab and chemotherapy in this population.

Xanthate-modified alginates for the removal of Pb(II) and Ni(II) from aqueous solutions: A brief analysis of alginate xanthation.

Mining is the most common activity that introduces heavy metal ions into aquatic ecosystems, especially in low income-developing nations where governments are implementing stricter regulations for industrial wastewater. In this context, this work is focused on the application of xanthate-modified alginates for the removal of Pb(II) and Ni(II) from aqueous solutions. In order to confirm the presence of xanthate groups alongside alginate chains, characterization by second-derivative FT-IR was carried out and significance evidence attributed to xanthate groups was found at around 1062-1079 cm-1, 829-845 cm-1 and 620-602 cm-1. In addition to this, thermogravimetric analysis and differential scanning calorimetry were employed to explore thermal properties of modified alginates. According to these results, enthalpy changes (∆H) characteristic of dehydration and collapse of biopolymeric structure were estimated as +11.41 J/g and -6.83 J/g, respectively. Furthermore, the presence of S element was confirmed by EDS mapping technique, whereas FESEM image showed a cracked and homogeneous surface distribution. On the other hand, the effect of important parameters such as pH, dosage, initial concentration as well as Langmuir and Freundlich isotherm were deeply discussed. Finally, rheological measurements were performed aiming to investigate the gel-like viscoelastic features associated to nickel xanthate compound.

Xanthation of alginate for heavy metal ions removal. Characterization of xanthate-modified alginates and its metal derivatives.

Xanthates are widely used in mining industry as collectors for its high affinity towards metal sulfides and precious metal ores. The possibility of using alginate for xanthation has not been explored yet despite the feasibility by the presence of hydroxyl groups alongside the polymeric chains. Therefore, this work aims to evaluate the alginate as a matrix for xanthation and its application on heavy metal ions removal. In order to obtain green materials, important pararmeter were explored such as the effect of reaction time (4-12 h), type of base (NaOH/KOH) and amount of carbon disulfide (2-10%v/v). Xanthated alginates were analyzed by NMR techniques and evidence of ß-elimination was detected at 5.45 ppm. Furthermore, the presence of S element was confirmed by EDS mapping technique, while XRD showed a semi-crystalline structure. On the other hand, the chemical shifts of δ(C=S) and ν(C=S) bands were found around 863-805 cm-1 and 662-602 cm-1 respectively. Also, a shoulder at 182 ppm is appreciated by NMR in solid state attributed to CS group. According to FESEM analyses, morphology of xanthated alginates is affected by interaction with heavy metal ions. Finally, suitable materials for the removal of heavy metal ions were established at optimum pH values.

Bibliometric analysis and evaluation of the journal Medicina Oral Patología Oral y Cirugía Bucal (2008-2018).

BACKGROUND: In 2008 the journal Medicina Oral Patología Oral y Cirugía Bucal was included in Journal Citation Reports. To appraise its evolution and current status, this study carried out a bibliometric analysis and evaluation of the journal for the period 2008-2018. MATERIAL AND METHODS: From the Web of Science, Journal Citation Reports we obtained the indicators Journal Impact Factor (JIF), 5-year JIF, JIF without self-cites, Eigenfactor score and Article Influence score (2010-2017); and from the Core Collection database the following variables: number and article types, institutions and countries of origin of the authors (2008-2018), and the variable cited and citing journal data in 2017. Twelve articles/year (n=132) were randomly selected to gather: the time between submittal and acceptance of an article, number of authors/article, representation of each section, gender of first author, and funding. RESULTS: The journal occupied the third quartile of the JCR from 2010 to 2017, when it moved up to the second quartile. From 2008 to 2018 it published a total of 1,518 documents, 90% articles and 9.5% reviews. Sixty countries were represented, 48.68% of the documents coming from Spain, and overall 1,293 institutions were involved. Between submittal and acceptance of articles, the average time was 134.42 days, without differences between years. The mean of authors/article was 5.15, increasing over time. The sections most represented were Oral Medicine and Pathology, and Oral Surgery. There were no differences regarding the gender of the first author, and in general the authors did not provide information about funding received. CONCLUSIONS: The bibliometric results indicate a steadily improving position of this journal, along with a tendency to reduce self-citation. The time between reception of an article and its acceptance was very stable, the number of authors per article showed an increase, and there was a nearly equal representation of males and females as the first author.

Guía práctica de manejo inicial del dolor abdominal recurrente en la infancia / Practical guide for initial management of recurrent abdominal pain in children

El dolor abdominal recurrente (DAR) en niños es uno de los motivos de consulta más frecuentes por enfermedad crónica. Se estima que afecta a un 10% de niños y dolescentes (4-25% según distintas series)(1) y con frecuencia puede tener una gran repercusión familiar, económica y en la calidad de vida del paciente, interferir con su actividad diaria, provocar absentismo escolar, pruebas complementarias, visitas a urgencias e incluso hospitalizaciones(1,2). Predomina en niñas hasta la pubertad (odds ratio para el sexo femenino 1,5), pero después la frecuencia es similar en ambos sexos(3). La mayoría de los casos no tendrán una causa orgánica subyacente ni entrañan gravedad, pero hay que recordar la incertidumbre del médico que debe enfrentarse a esa consulta reiterada, ante la posibilidad de no estar realizando todas las pruebas complementarias necesarias para llegar a un diagnóstico correcto, dada su escasa especificidad clínica habitual. El temor a que se descubra posteriormente en nuestro paciente una causa orgánica o infrecuente para el mismo que hayamos podido pasar por alto, hace que en muchos casos nos enfrentemos con inseguridad a esta situación. Trataremos de hacer comprender mejor este cuadro, simplificando el problema, quizás en exceso, pero en aras a intentar ayudar en su manejo en la práctica clínica

No disponible

Resultados funcionales de hemiartroplastía bipolar en pacientes mayores de 65 años con fracturas intracapsulares de cadera / Functional results of bipolar hemiarthroplasty in patients over 65 years of age with intracapsular hip fractures

Resumen: Introducción: La hemiartroplastía bipolar (HA) es una alternativa para el tratamiento de las fracturas desplazadas de cuello femoral en pacientes de edad avanzada con baja demanda funcional y comorbilidades asociadas. El objetivo fue describir la funcionalidad en pacientes mayores de 65 años con fracturas intracapsulares de cadera tratados con HA. Material y métodos: Revisión retrospectiva de pacientes mayores de 65 años entre Enero de 2012 y Mayo de 2017. Se evaluó con la escala de Harris (HHS) y Oxford a los seis meses y al año posterior a la cirugía. Se documentaron las complicaciones y la mortalidad durante el primer año postquirúrgico. Resultados: 48 casos (12 hombres; 36 mujeres), edad promedio de 80.8 ± 7.7 años. Comorbilidades más frecuentes: hipertensión arterial (77.1%), osteoporosis (37.5%), diabetes (33.3%) e hipotiroidismo (29.2%). El porcentaje de complicaciones postoperatorias asociadas fue de 8.3% (cuatro casos). La mediana del HHS a los seis y 12 meses fue de: 90.5 (DE: 77.5-96.0) y 96 (DE: 92-98), respectivamente. La escala de Oxford fue de 45.5 (DE: 38.5-48.0) a los seis meses y de 47.0 (DE: 43.5-48) al año postoperatorio. El 4.2% (dos casos) fallecieron durante el primer año postquirúrgico y ninguno estuvo asociado al procedimiento. Discusión: La HA ofrece buenos resultados funcionales en pacientes mayores de 65 años, con una tasa baja de complicaciones. En nuestra serie y en el corto plazo no se observó mortalidad asociada al procedimiento quirúrgico.

Abstract: Introduction: Bipolar hemiarthroplasty is an alternative for the treatment of displaced femoral neck fractures in elderly patients with low functional demand and associated comorbidities. The goal was to describe functionality in patients over 65 years of age with intracapsular fractures of the hip. Material and methods: Retrospective review of patients over 65 years of age between January 2012 and May 2017. It was evaluated with the Harris Hip Score (HHS) and Oxford scale at six months and the year after surgery. Complications and mortality were documented during the first post-surgical year. Results: 48 cases (12 men; 36 women), average age of 80.8 ± 7.7 years. Most common diseases: high blood pressure (77.1%), osteoporosis (37.5%), diabetes (33.3%) hypothyroidism (29.2%). The percentage of associated postoperative complications was 8.3% (four cases). The median HHS at six and 12 months was: 90.5 (DE: 77.5-96.0) and 96 (DE: 92-98), respectively. The Oxford scale was 45.5 (DE: 38.5-48.0) at six months and 47.0 (DE: 43.5-48.0) per postoperative year. 4.2% (two cases) died during the first post-surgical year and none were associated with the procedure. Discussion: HA provides good functional outcomes in patients over 65 years of age, with a low rate of complications. No mortality associated with the surgical procedure was observed in our series and in the short term.

[Functional results of bipolar hemiarthroplasty in patients over 65 years of age with intracapsular hip fractures]. / Resultados funcionales de hemiartroplastía bipolar en pacientes mayores de 65 años con fracturas intracapsulares de cadera.

INTRODUCTION: Bipolar hemiarthroplasty is an alternative for the treatment of displaced femoral neck fractures in elderly patients with low functional demand and associated comorbidities. The goal was to describe functionality in patients over 65 years of age with intracapsular fractures of the hip. MATERIAL AND METHODS: Retrospective review of patients over 65 years of age between January 2012 and May 2017. It was evaluated with the Harris Hip Score (HHS) and Oxford scale at six months and the year after surgery. Complications and mortality were documented during the first post-surgical year. RESULTS: 48 cases (12 men; 36 women), average age of 80.8 ± 7.7 years. Most common diseases: high blood pressure (77.1%), osteoporosis (37.5%), diabetes (33.3%) hypothyroidism (29.2%). The percentage of associated postoperative complications was 8.3% (four cases). The median HHS at six and 12 months was: 90.5 (DE: 77.5-96.0) and 96 (DE: 92-98), respectively. The Oxford scale was 45.5 (DE: 38.5-48.0) at six months and 47.0 (DE: 43.5-48.0) per postoperative year. 4.2% (two cases) died during the first post-surgical year and none were associated with the procedure. DISCUSSION: HA provides good functional outcomes in patients over 65 years of age, with a low rate of complications. No mortality associated with the surgical procedure was observed in our series and in the short term.

INTRODUCCIÓN: La hemiartroplastía bipolar (HA) es una alternativa para el tratamiento de las fracturas desplazadas de cuello femoral en pacientes de edad avanzada con baja demanda funcional y comorbilidades asociadas. El objetivo fue describir la funcionalidad en pacientes mayores de 65 años con fracturas intracapsulares de cadera tratados con HA. MATERIAL Y MÉTODOS: Revisión retrospectiva de pacientes mayores de 65 años entre Enero de 2012 y Mayo de 2017. Se evaluó con la escala de Harris (HHS) y Oxford a los seis meses y al año posterior a la cirugía. Se documentaron las complicaciones y la mortalidad durante el primer año postquirúrgico. RESULTADOS: 48 casos (12 hombres; 36 mujeres), edad promedio de 80.8 ± 7.7 años. Comorbilidades más frecuentes: hipertensión arterial (77.1%), osteoporosis (37.5%), diabetes (33.3%) e hipotiroidismo (29.2%). El porcentaje de complicaciones postoperatorias asociadas fue de 8.3% (cuatro casos). La mediana del HHS a los seis y 12 meses fue de: 90.5 (DE: 77.5-96.0) y 96 (DE: 92-98), respectivamente. La escala de Oxford fue de 45.5 (DE: 38.5-48.0) a los seis meses y de 47.0 (DE: 43.5-48) al año postoperatorio. El 4.2% (dos casos) fallecieron durante el primer año postquirúrgico y ninguno estuvo asociado al procedimiento. DISCUSIÓN: La HA ofrece buenos resultados funcionales en pacientes mayores de 65 años, con una tasa baja de complicaciones. En nuestra serie y en el corto plazo no se observó mortalidad asociada al procedimiento quirúrgico.

Chemical modification of alginate with cysteine and its application for the removal of Pb(II) from aqueous solutions.

It has been synthesized, characterized and tested a new biomaterial AlgS (sodium alginate functionalized with cysteine) to remove Pb(II) in aqueous media. The maximum Pb(II)-sorption capacity of AlgS (Qmax = 770 mg·g-1) is between almost two and nine times higher than other alginate-materials reported in the literature. Techniques, such as TGA/DSC, SEM/EDS, BET, FTIR, UV-Vis, XRD and 13C solid state-NMR have been used to study the chemical-modification of alginate at oxidation and aminofication stages. The formation of the imine intermediate (C=N), after 24 h of reaction was identified by a UV band at 348 nm. Typical IR-bands of AlgS were identified at 2970, 955, 949 and 1253 cm-1 which are associated to CH, SPb, SH and CN stretching vibrations, respectively. 13C solid state-NMR spectra of AlgS, show peaks at 33-38 ppm and 55-60 ppm associate to δ (HS-CH2-) of cysteine and δ (CN) respectively. The ΔH° and ΔG° negative values for Pb(II) sorption indicate that it is an exothermic process and occur spontaneously. Finally, it was found that the Pb(II) sorption on AlgS is significantly affected by the presence of cationic (Na+, Mg2+ and Al3+) and anionic (Cl-, NO3-) co-ions.

Chemical modification of sodium alginate with thiosemicarbazide for the removal of Pb(II) and Cd(II) from aqueous solutions.

A new material (AlgOx-TSC), based on alginate (Alg) chemically modified with thiosemicarbazide (TSC), has been synthesized and tested as an effective biomaterial to remove Pb(II) and Cd(II) ions in aqueous solutions. The synthesis was carried out by controlling the following steps, i/partial oxidation process of alginate in NaIO4 to obtain AlgOx, ii/reacting of AlgOx, at 40-45 °C, with TSC in NaBH4. AlgOx-TSC has been characterized by Field Emission Scanning Electron Microscopy (FESEM/EDS), Fourier Transform Infrared Spectroscopy (ATR-IR), solid state 13C NMR spectroscopy and Point of Zero Charge (pHPZC) measuremenmts. In order to enhance the sorption process, the effect of contact time, sorbent dosage, initial concentration and reusability of the novel sorbent were investigated becoming the AlgOx-TSC a promising material capable of removing high concentrations of heavy metal ions such as Pb(II) (up to 950 mg/g at pH 3) and Cd(II) (up to 300 mg/g at pH 7) in aqueous solutions.

Impact of symptomatic skeletal events on health-care resource utilization and quality of life among patients with castration-resistant prostate cancer and bone metastases.

BACKGROUND: Data regarding the impact of symptomatic skeletal events (SSEs) on health economics and patient-reported outcomes in men with castration-resistant prostate cancer (CRPC) and bone metastases from a clinical setting are lacking. Hence, this study aimed to quantify the effects of SSEs on health-care resource utilization (HRU), health-related quality of life (HRQoL) and pain in men with CRPC metastasized to bone. METHODS: This cohort study included men with CRPC and bone metastasis treated at a tertiary center during December 1996-July 2015. SSEs, including pathological fracture, radiation to bone, spinal cord compression and bone surgery, as well as HRU were identified retrospectively through medical records and clinical database. A subset of surviving patients completed Functional Assessment of Cancer Therapy-Prostate (FACT-P) and Brief Pain Inventory-Short Form (BPI-SF) questionnaires. The incremental effect of SSEs on HRU was evaluated using multivariable generalized linear regression. Questionnaire scores were compared using effect sizes (ES); ES⩾0.33 indicated meaningful differences between SSE and non-SSE cohorts. Lower scores suggest lower HRQoL and pain. RESULTS: Of the 832 patients, 207 developed ⩾1 SSE (mean 1.5±0.8) during follow-up (median 2.1 years). Radiation to bone was the most common SSE (84.1%). SSE cohort had significantly higher emergency room (incidence rate ratio (IRR)=1.48; P=0.006), outpatient (IRR=1.17; P=0.005) and inpatient (IRR=1.74; P<0.001) visits. Of the 107 eligible survey patients, 103 (96.3%) responded. SSE cohort had lower mean FACT-P functional well-being (17.5 vs 19.8; P=0.158; ES=0.36), higher mean pain severity (2.5 vs 1.6; P=0.048; ES=0.47) and worst pain scores (3.6 vs 2.3; P=0.033; ES=0.50) compared with the non-SSE cohort, indicating meaningful differences between cohorts. CONCLUSIONS: This study demonstrated high economic and HRQoL burden of SSEs. The findings underscore the need for better supportive and disease-modifying treatments for these patients.

Evaluación mecánica de la conexión externa e interna en implantes de titanio / Mechanical evaluation of external and internal connection titanium implants

INTRODUCCIÓN: El objetivo de este estudio fue comparar, in vitro, la resistencia mecánica de sistemas hexagonales de conexión interna y externa en implantes dentales sometidos a fuerzas estáticas compresivas, de flexión y de compresión-flexión. MATERIALES Y MÉTODOS: Fueron conformados 18 ensambles, nueve de cada tipo de conexión, externa (CE) e interna (CI), de la casa comercial Lifecore(R) Los implantes utilizados eran de 3,75 mm de diámetro y 13 mm de longitud en ambos grupos. Las pruebas se realizaron en una máquina universal Instron(R), con carga vertical estática progresiva en diferentes angulaciones hasta producir la deformación máxima del sistema (0º: compresión, 45º: compresión-flexión y 90º: flexión). RESULTADOS: Los mayores valores registrados para carga elástica límite se presentaron en las pruebas realizadas con cargas a 0º en los grupos de CI (1733.5 N) y CE (1619.5 N) y los valores más bajos fueron registrados para las cargas aplicadas a 90º en CI y CE con 267 N y 226 N respectivamente. El grupo de conexión interna, en los diferentes grupos de aplicación de la carga, presentó resultados más homogéneos de acuerdo con el coeficiente de variación (<20%) mientras el grupo de CE presentó mayor coeficiente de variación. DISCUSIÓN: Se observa que la conexión interna tiende a poseer una mayor carga elástica límite. Además, las zonas de fractura tienen diferente apariencia, lo cual puede indicar que los sistemas responden diferente a las cargas. Estas diferencias deben influir en el comportamiento de los sistemas en otras exigencias como aflojamiento y cargas cíclicas

INTRODUCTION: The purpose of this study was to compare, in vitro, mechanical strength ofive tlat internal and external hexagonal systems used as dental implants submitted to compressive, flexion and compression-flexion forces. MATERIAL AND METHODS: 18 assemblies were used, nine internal hex Renova(R) implants (IC) and nine external hex RBM(R) implants (EC) (3.75×13 mm). Samples were tested in an Instron(R) universal machine. A static progressive load with the sample positioned relative to the axis machine at vertical (0º), angular (45º) and horizontal (90º) positions until deformation occurs. RESULTS: The greatest values for elastic limit load were obtained for a vertical load (0º) in the IC group (1733.5N) and EC (1619.5N). On the other hand, minimum values were obtained for horizontal load (90º) in IC and EC with 267N and 226N respectively. The IC group showed more homogeneous results in agreement with the variation coefficient (<20%), meanwhile the EC group showed the greater variation coefficient. DISCUSSION: The IC tends to have higher elastic limit load. Besides, the fractured zones showed different shapes indicating that each system have different responses under load. In that way, this difference could be representative under cyclic load

Diagnóstico prenatal de trisomía 21 y holoprosencefalia semilobar. Presentación de una asociación poco frecuente / Prenatal diagnosis of trisomy 21 and semilobar holoprosencephaly. Presentation of a rare association

Se presenta el primer caso reportado en la República de Colombia y uno de los pocos en la literatura médica mundial, de la asociación de trisomía 21 y holoprosencefalia. Paciente recién nacido, masculino, hijo de madre primípara sana de 19 años de edad. Con ultrasonido obstétrico realizado a las 27 semanas de gestación, se encontró feto con dilatación de ambos ventrículos cerebrales, holoprosencefalia semilobar, labio y paladar fisurados. A la madre se le realizó, ecografía de detalle y amniocentesis para estudio citogenético fetal. Se practicó cesárea a las 38 semanas, cuyo producto presentó peso de 2.200 g, talla de 46 cm, perímetro cefálico de 28 cm, perímetro torácico de 28,5 cm y perímetro abdominal de 27 cm. Puntuación de Apgar de 6 al primer minuto, 6 a los 5 min y 9 a los 10 min. Físicamente se observó cara de luna llena, oblicuidad mongoloide de las fisuras palpebrales, hipoplasia nasal, labio y paladar fisurados, micrognatia. La tomografía cerebral axial computarizada simple y con contraste mostró holoprosencefalia semilobar y labio fisurado. A las 25 h de vida, murió de paro respiratorio. El cariotipo prenatal presentó fórmula cromosómica 47, XY, +21, por el método de bandas «G». El estudio citogenético posnatal, realizado con sangre de cordón umbilical y con el empleo de la técnica de FISH y la sonda LSI 13/21, mostró la fórmula: nuc ish (D13ZX2) (D21ZX3)[30]. Se discute la etiología citogenética del cromosoma 21 y la génica de la holoprosencefalia, pensando en el hecho de que alteraciones citogenéticas y génicas podrían trabajar de manera sinérgica y concordar en su expresión con el postulado del múltiple-hit process (AU)

We present the first case reported in the Republic of Colombia of associated trisomy 21-holoprosencephaly, one of the few in the world literature. The patient was a male newborn, the son of a healthy primiparous 19 year old. An obstetric sonogram at 27 weeks gestation revealed the foetus with both cerebral ventricles dilated, semilobar holoprosencephaly and cleft lip and palate. The mother received a detailed ultrasound scan and amniocentesis for foetal cytogenetic study. A caesarean section was performed at 38 weeks. The newborn weighed 2200 g and was 46 cm long. The head circumference was 28 cm; thoracic girth, 28.5 cm; and abdominal girth, 27 cm. Apgar score was 6 at 1 min, 6 at 5 min and 9 at 10 min. Physically, the newborn had a full moon face, mongoloid obliquity of the palpebral fissure, nasal bone hypoplasia, micrognathia and cleft lip and palate. Simple and contrast computed axial tomography of the brain showed semilobar holoprosencephaly and cleft lip. At 25 h of life, the newborn expired from respiratory arrest. Prenatal chromosome analysis presented a 47, XY, +21 G-band karyotype. Postnatal cytogenetic analysis, performed on umbilical cord blood using the fluorescent in situ hybridisation (FISH) technique with a locus specific identifier (LSI) 13/21 probe, showed the formula: nuc ish (D13ZX2), (D21ZX3) [30]. The cytogenetic aetiology of chromosome 21 and the holoprosencephaly gene are discussed, focusing on the fact that cytogenetic and gene alterations could function synergically and coincide in their expression with the postulate of the multiple-hit process (AU)

Do skeletal-related events predict overall survival in men with metastatic castration-resistant prostate cancer?

BACKGROUND: Skeletal-related events (SREs) including pathologic fracture, spinal cord compression, radiation to bone and surgery to bone, are common in men with bone metastatic castration-resistant prostate cancer (mCRPC). Men with mCRPC are at high risk of death. Whether SREs predict mortality is unclear. We tested the association between SREs and overall survival (OS) in a multiethnic cohort with bone mCRPC, controlling for key covariates unavailable in claims data such as bone pain, number of bone metastases and PSA doubling time (PSADT). METHODS: We collected data on 233 men diagnosed with nonmetastatic castration-resistant prostate cancer (CRPC) in 2000-2013 at two Veterans Affairs hospitals who later progressed to bone metastases. First occurrence of SRE and OS were collected from the medical records. Cox models were used to test the association between SRE and OS, treating SRE as a time-dependent variable. We adjusted for age, year, race, treatment center, biopsy Gleason, primary treatment to the prostate, PSA, PSADT, months from androgen deprivation therapy to CRPC, months from CRPC to metastasis and number of bone metastases at initial bone metastasis diagnosis. In a secondary analysis, we also adjusted for bone pain. RESULTS: During follow-up, 88 (38%) patients had an SRE and 198 (85%) died. After adjusting for risk factors, SRE was associated with increased mortality (hazard ratio (HR)=1.67; 95% confidence interval (CI) 1.22-2.30; P=0.001). When bone pain was added to the model, the association of SREs and OS was attenuated, but remained significant (HR=1.42; 95% CI 1.01-1.99; P=0.042). CONCLUSIONS: SREs are associated with increased mortality in men with bone mCRPC. Further studies on the impact of preventing SREs to increase survival are warranted.

Esofagitis eosinofílica / Eosinophilic esophagitis

No disponible

Zika virus in Panamá and Latinamérica: Clinical and molecular aspects of an emerging issue.

The purpose of this review is to provide Latin America's and the region's healthcare professionals with an overview of the current situation related to Zika virus (ZIKAV), and at the same time, to provide relevant clinical and molecular knowledge against this emerging problem. We expect to have a positive impact in diagnostic, surveillance and treatment of this viral disease, specially in those endemic communities, as part of a collective effort against the virus. This review will be distributed as hard-copy and online as a public health and epidemiological initiative.

El propósito de esta revisión es presentar al equipo de salud latinoamericano y de la región del caribe un panorama de la situación actual con el virus Zika (ZIKAV), y al mismo tiempo, proveer conocimiento clínica y molecular relevante para enfrentar este problema emergente. Esperamos que esta revisión tenga un impacto positivo en el diagnóstico, vigilancia, y tratamiento de esta enfermedad viral, especialmente en comunidades endémicas, como parte de un esfuerzo colectivo para enfrentar este virus. Este manuscrito será distribuido electrónicamente y físicamente como una iniciativa de salud pública y epidemiologica.

New and Common Haplotypes Shape Genetic Diversity in Asian Tiger Mosquito Populations from Costa Rica and Panamá.

The Asian tiger mosquito, Aedes albopictus (Skuse) (Diptera: Culicidae), is a vector of several human pathogens. Ae. albopictus is also an invasive species that, over recent years, has expanded its range out of its native Asia. Ae. albopictus was suspected to be present in Central America since the 1990s, and its presence was confirmed by most Central American nations by 2010. Recently, this species has been regularly found, yet in low numbers, in limited areas of Panamá and Costa Rica (CR). Here, we report that short sequences (∼558 bp) of the mitochondrial cytochrome oxidase subunit 1 (COI) and NADH dehydrogenase subunit 5 genes of Ae. albopictus, had no haplotype diversity. Instead, there was a common haplotype for each gene in both CR and Panamá. In contrast, a long COI sequence (∼1,390 bp) revealed that haplotype diversity (±SD) was relatively high in CR (0.72±0.04) when compared with Panamá (0.33±0.13), below the global estimate for reported samples (0.89±0.01). The long COI sequence allowed us to identify seven (five new) haplotypes in CR and two (one new) in Panamá. A haplotype network for the long COI gene sequence showed that samples from CR and Panamá belong to a single large group. The long COI gene sequences suggest that haplotypes in Panamá and CR, although similar to each other, had a significant geographic differentiation (Kst=1.33; P<0.001). Thus, most of our results suggest a recent range expansion in CR and Panamá.

Hepatocellular carcinoma surveillance rates in commercially insured patients with noncirrhotic chronic hepatitis B.

American association for the study of liver diseases (AASLD) and European Association for the Study of the Liver (EASL) guidelines recommend biannual hepatocellular carcinoma (HCC) screening for noncirrhotic patients with chronic hepatitis B infection (HBV), yet there are no data estimating surveillance rates or factors associated with surveillance. We performed a retrospective cohort study of US patients using the Truven Health Analytics databases from 2006 to 2010 and identified patients with noncirrhotic chronic HBV. Surveillance patterns were characterized using categorical and continuous outcomes, with the continuous measure of the proportion of time 'up to date' with surveillance (PUTDS), with the 6-month interval following each ultrasound categorized as 'up to date'. During a median follow-up of 26.0 (IQR: 16.2-40.0) months among 4576 noncirrhotic patients with chronic HBV (median age: 44 years, IQR: 36-52), only 306 (6.7%) had complete surveillance (one ultrasound every 6-month interval), 2727 (59.6%) incomplete (≥1 ultrasound) and 1543 (33.7%) none. The mean PUTDS was 0.34 ± 0.29, and the median was 0.32 (IQR: 0.03-0.52). In multinomial logistic regression models, patients diagnosed by a nongastroenterologist were significantly less likely to have complete surveillance (P < 0.001), as were those coinfected with HBV/HIV (P < 0.001). In linear regression models, nongastroenterologist provider, health insurance subtype, HBV/HIV coinfection, rural status and metabolic syndrome were independently associated with decreased surveillance. Patients with HIV had an absolute decrease in the PUTDS of 0.24, while patients in less populated rural areas had an absolute decrease of 0.10. HCC surveillance rates in noncirrhotic patients with chronic HBV in the United States are poor and lower than reported rates of HCC surveillance in cirrhotic patients.

Outcomes of off-label drug uses in hospitals: a multicentric prospective study.

PURPOSE: The study aims to assess the clinical evidence, outcome and cost of off-label use of medicines in the hospital setting. METHODS: A multicentric prospective cohort study of patients treated with off-label medicines was carried out in five tertiary hospitals from May 2011 to May 2012. Information on clinical characteristics of patients, drugs, outcomes and costs was collected. Patients were followed up to 6 months, and information was assessed by reviewing clinical records and interviewing physicians. RESULTS: A total of 226 patients were included. The median (interquartile range (IQR)) age of patients was 46 (33-62) years; 59 % were women. Patients had received a median of three previous treatments, and a lack of response (or suboptimal) was the main reason for off-label use (72.1 %). A total of 232 off-label medicines were administered for 102 different indications. The most frequent medicines were rituximab (49; 21.1 %), botulinum toxin (25; 10.7 %) and omalizumab (14; 6.0 %). In 117 (51.8 %) cases, the level of clinical evidence for their use was low. A partial clinical response was observed in 82 patients (36.3 %), complete response in 71 (31.4 %) and stabilization in 11 (4.9 %). A total of 58 (26.5 %) patients had adverse effects, which in 11 (4.9 %) were severe. The median (IQR) cost per patient was 2,943.07 (541.9-5,872.54). CONCLUSIONS: There was a high variability of off-label medicines and indications. Although the clinical evidence of off-label medicines was often low, clinical response was observed in many patients with previous multiple treatment failure, but at the expense of some adverse effects and a high cost. Registers of patients would be helpful for clinical decisions, although clinical trials are needed.