Mutations in Coding and Non-Coding Regions in Varicella-Zoster Virus Causing Fatal Hemorrhagic Fever Without Rash in an Immunocompetent Patient: Case Report.

INTRODUCTION: We report the case of a fatal hemorrhagic varicella primary infection in an immunocompetent man and whole-genome characterization of the virus for the investigation of biomarkers of virulence. CASE: A 38-year-old patient born in Nigeria presented to the emergency department with abdominal pain and subsequently developed fatal hemorrhagic disease without skin rash. Extensive laboratory tests including serology and PCR for arenaviruses, bunyaviruses and ebolaviruses were negative. Varicella-zoster virus (VZV) PCR of sera, liver and spleen tissue samples from autopsy revealed the presence of VZV DNA. Primary infection by varicella-zoster virus with hemorrhagic manifestations was diagnosed after virological testing. The VZV genome was sequenced using a mWGS approach. Bioinformatic analysis showed 53 mutations across the genome, 33 of them producing non-synonymous variants affecting up to 14 genes. Some of them, such as ORF11 and ORF 62, encoded for essential functions related to skin or neurotropism. To our knowledge, the mutations reported here have never been described in a VZV causing such a devastating outcome. DISCUSSION: In immunocompetent patients, viral factors should be considered in patients with uncommon symptoms or severe diseases. Some relevant mutations revealed by using whole genome sequencing (WGS) directly from clinical samples may be involved in this case and deserves further investigation. CONCLUSION: Differential diagnosis of varicella-zoster virus in immunocompetent adults should be considered among patients with suspected VHF, even if the expected vesicular rash is not present at admission and does not arise thereafter. Whole genome sequencing of strains causing uncommon symptoms and/or mortality is needed for epidemiological surveillance and further characterization of putative markers of virulence. Additionally, this report highlights the recommendation for a VZV vaccination policy in non-immunized migrants from developing countries.

Phlebovirus-associated diseases transmitted by phlebotominae in Spain: Are we at risk?

The genera Phlebovirus transmitted by Diptera belonging to the Psychodidae family are a cause of self-limited febrile syndrome in the Mediterranean basin in summer and autumn. Toscana virus can also cause meningitis and meningoencephalitis. In Spain, Toscana, Granada, Naples, Sicily, Arbia and Arrabida-like viruses have been detected. The almost widespread distribution of Phlebotomus genus vectors, and especially Phlebotomus perniciosus, in which several of these viruses have been detected, makes it very likely that there will be regular human infections in our country, with this risk considered moderate for Toscana virus and low for the other ones, in areas with the highest vector activity. Most of the infections would be undiagnosed, while only Toscana virus would have a greater impact due to the potential severity of the illness.

Hospitalización domiciliaria en un área rural, ¿una alternativa a la hospitalización tradicional? / Home care services provided by hospital in a rural area, an alternative to traditional hospitalization?

INTRODUCCIÓN: El servicio de hospitalización domiciliaria en el área rural es un servicio poco conocido en el resto del ámbito sanitario. Al mismo tiempo existe poca literatura al respecto por lo que con este estudio queremos estudiar las características clínicas, la estancia media y la tasa de reingresos de los pacientes que ingresan en hospitalización domiciliaria en comparación a los pacientes que ingresan en planta de medicina interna pertenecientes a un hospital comarcal de un área rural (Hospital de TresMares). MÉTODO: Estudio descriptivo comparativo retrospectivo que incluye un total de 200 pacientes (100 ingresados en hospitalización domiciliaria y 100 ingresados en planta) del hospital de TresMares. RESULTADOS: La complejidad de los pacientes que ingresan en planta es superior a los que ingresan en hospitalización domiciliaria requiriendo al mismo tiempo de mayor uso de recursos. La eficacia, entendida como tasa de reingreso, en hospitalización a domicilio es similar a la de los pacientes de la planta. Se demuestra que la hospitalización domiciliaria puede ser una alternativa a la hospitalización tradicional en un área rural. CONCLUSIONES: Se demuestra que la hospitalización domiciliaria puede ser una alternativa a la hospitalización tradicional en un área rural

INTRODUCTION: Hospital home care in a rural area is a hospital care little known in health field. At the same time there is little literature so we want to study the clinical characteristics, the average stay and the readmission rate of patients admitted to home hospitalization compared to patients admitted to the internal medicine hospitalization to a regional hospital in a rural area (Hospital de TresMares). METHOD: retrospective comparative descriptive study includes 200 patients (100 patients admitted to home hospitalization and 100 patients admitted to the hospital). RESULTS: the complexity of the patients admitted to the hospital is greater than those admitted to home hospitalization, while requiring greater use of resources. The efficacy, understood as re admission rate, in hospitalization at home is similar that the patients who are admitted in the hospital. CONCLUSIONS: home hospitalization can be an alternative to tradicional hospitalization in a rural are

Hantavirus Pulmonary Syndrome in Traveler Returning from Nepal to Spain.

Most human hantavirus infections occur in Asia, but some cases have been described in Europe in travelers returning from Asia. We describe a case of hantavirus pulmonary syndrome in a previously healthy traveler occurring shortly after he returned to Spain from Nepal. Serologic tests suggested a Puumala virus-like infection.

Aspiración de cuerpo extraño en paciente adulto durante un procedimiento dental. A propósito de un caso / Foreign-matter aspiration in an adult patient during a dental procedure. A case report

La aspiración de cuerpos extraños en las vías aéreas puede ser potencialmente mortal. Estos fenómenos ocurren sobre todo en niños, siendo la primera causa de muerte accidental en menores de un año. No obstante, que esto ocurra en pacientes adultos es menos frecuente. La clínica suele ser muy variable, pudiendo persistir la sensación de ahogo y disnea tras la aspiración del cuerpo extraño o bien una vez concluida la aspiración, encontrarse asintomático. Una buena anamnesis es primordial para orientar el diagnóstico y desobstruir la vía aérea lo más pronto posible. El tratamiento de elección en pacientes adultos es el broncoscopio flexible, también llamado fibrobroncoscopio. A continuación, describimos un caso de un paciente de 44 años que acude a Urgencias por presentar accidentalmente una aspiración de un destornillador dental. Aunque se encontraba asintomático al momento de la valoración, las características de dicho cuerpo extraño (tamaño, punzante, localización, etc.) hicieron necesaria una derivación a un centro de referencia y una broncoscopia de urgencia

The aspiration of foreign matter into the airways can be potentially fatal. This phenomenon occurs primarily in children, constituting the leading cause of death in children under one year old. However, its occurrence in adult patients is less frequent. Symptoms tend to vary greatly, from a persistent feeling of choking or dyspnea after the aspiration of the foreign matter to being asymptomatic after the aspiration. A thorough medical history is key to guide the diagnosis and clear the airway as soon as possible. The treatment of choice in adult patients is flexible bronchoscopy, also known as fibrobronchoscopy. Below, we will describe the case of a 44-year-old patient who went to the emergency room after accidentally aspirating a dental screwdriver. Although he was asymptomatic at the time of the examination, the characteristics of the foreign matter (size, sharpness, location, etc.) made referral to a reference center and an emergency bronchoscopy necessary

Results of a multi-faceted educational intervention to prevent peripheral venous catheter-associated bloodstream infections.

Peripheral venous catheter-associated bloodstream infections (PVC-BSIs) lead to prolonged hospitalization, morbidity and increased costs. The impact of infection-prevention measures on the rate of PVC-BSIs in a university hospital in Spain was assessed. An active surveillance programme was initiated in 2015, which revealed a high PVC-BSI incidence ratio (0.48/1000 patient-days). A bundle aimed at nurses, medical staff and patients was implemented, and a Catheter Infection Team (CIT) was set up. The intervention achieved a decrease in PVC-BSI rate: 0.34 in 2016, 0.29 in 2017, and 0.17 in 2018. The decline was greatest for Gram-negative PVC-BSIs (67.6% in 2015, 35.3% in 2018).

In utero negativization of Zika virus in a foetus with serious central nervous system abnormalities.

We describe a case of a pregnant woman with Zika virus (ZIKV) infection and a foetus with severe brain malformations. ZIKV tested positive in amniotic fluid at 19 weeks but was negative at delivery. The newborn did not meet the case definition of congenital ZIKV syndrome because neither ZIKV RNA nor IgM antibodies were detected; however, prenatal brain lesions were confirmed after birth (Graphical Abstract).

Zika Virus: Cutaneous Manifestations in 3 Patients. / Virus Zika: manifestaciones cutáneas en 3 pacientes.

Zika virus infection should be suspected in travelers or immigrants with the signs or symptoms of a viral infection (rash, fever, joint pains, conjunctivitis, headache, etc.) and a compatible epidemiological history. Although cutaneous manifestations are among the most common clinical signs of Zika, they are not specific and very few images are available. We present 3 patients (2 travelers and 1 immigrant) in whom a rash was the presenting manifestation of Zika virus infection. Prompt diagnosis optimizes outcomes in these patients, improves the management of severe disease, and minimizes the risk of local transmission by Aedes albopictus, now a potential local vector for the virus due to its presence in areas along Spain's Mediterranean coast.

Sistema olfatorio y nariz en el nuevo baremo médico / Olfactory system and nose in the new medical scale

Los traumatismos nasales son los más frecuentes en los accidentes de tráfico con afectación facial. En el baremo, recogido en la Ley 35/2015 de Reforma del Sistema para la Valoración de los Daños y Perjuicios causados a las personas en accidentes de circulación, la clasificación y la valoración de las secuelas debido a estos traumatismos presentan ligeras modificaciones con relación al baremo anterior, así como la puntuación otorgada a cada una de ellas. Dentro de las secuelas, la desviación del tabique nasal es la más frecuente. La sinusitis debida a alteración en el drenaje de los senos paranasales y las alteraciones en el sentido del olfato por traumatismos de la lámina cribosa del etmoides y lesiones neurológicas tienen menor incidencia, siendo bastante infrecuente la pérdida parcial o total de la nariz (AU)

Nasal traumas are the most frequent in road traffic accidents with facial involvement. In the scale, contained in Law 35/2015 for the modification of the system for the assessment of damages caused to people involved in traffic accidents, the classification and sequels assessment due to these traumas presents slight differences in relation to the preceding scale as well as the score given to each of them. Among the sequels, the nasal septum deviation is the most frequent. Sinusitis due to the alteration in the paranasal sinus drainage and smell disorders owing to trauma of the cribiform plate of the ethmoid bone and neurological injuries have lower incidence, partial or complete nose loss is quite rare (AU)

El sistema cutáneo, nuevo capítulo en el baremo médico / The Skin, a new chapter in the Medical Scale

En el baremo médico contenido en el Real Decreto 8/2004 no se contemplan las alteraciones en el sistema cutáneo como responsables de menoscabo físico; se valora el menoscabo estético que produce en los lesionados. La inclusión de este capítulo en el nuevo baremo médico de autos viene determinada por la importancia de la piel, como sistema corporal, primordialmente por su función, reguladora de múltiples procesos en el individuo, y por su extensión. La valoración de las alteraciones del sistema cutáneo se realizará principalmente en quemaduras profundas y extensas, así como en lesiones que produzcan trastornos dermatológicos, teniendo en cuenta el porcentaje de superficie corporal afectada y el modo de reparación. La puntuación se puede complementar con las alteraciones funcionales en otros sistemas si las hubiera, así como con el perjuicio estético producido. El resto de las lesiones en la piel que no ocasionan menoscabo funcional, fundamentalmente cicatrices no patológicas, se valoran exclusivamente en el capítulo del perjuicio estético (AU)

The Medical Scale contained in the Real Decreto 8/2004 did not consider the skin alterations as the cause of the physical impairment, it only contemplated the aesthetic impairment which produce in the injuried person. Including this new chapter is determined by the importance of the skin as a essential body system due to its function as a regulatory system for a wide range of processes and its large area. The skin assesment will be mainly done in deep and extensive burns, as well as injuries which produce dermalotogic disorders, taking into acount the body surface percentage afected and the way it can be repared. The score can be supplemented with the functional disorders in other systems in case they exist, as well as the aesthetic damage suffered. The other skin injuries which do not cause functional impairment, essentialy no pathologic scars, will be assesed exclusively in the aesthetic damage chapter (AU)

El perjuicio estético en el nuevo baremo / The aesthetic damage in the new scale

La valoración del daño o perjuicio estético a lo largo de los últimos 25 años ha ido evolucionando y existen unas reglas de utilización en la actual tabla VI del Real Decreto 8/2004 aceptadas por todos. Pero a diferencia del menoscabo psicofísico, el perjuicio estético continúa generando controversia, debido fundamentalmente a que es un daño que se puede objetivar, pero con un gran componente de «subjetividad» por parte tanto del lesionado como del perito. En la Ley 35/2015 de reforma del sistema de valoración se mantienen las reglas de utilización del perjuicio estético contenido en el Real Decreto 8/2004 y aparecen por primera vez una serie de factores a tener en cuenta en su valoración (visibilidad, atracción, reacción y alteración relación interpersonal), así como ejemplos de cada grado del perjuicio. La horquilla de puntos en cada grado se incrementa en función de la gravedad del daño, con la finalidad de poder avanzar en una mejor cualificación y cuantificación de este daño (AU)

The physical harm o aesthetic damage assessment in the last 25 years has progressed and there are some rules accepted by everybody for the use of the actual scale of Table VI contained in the Royal Decree 8/2004. Unlike the psychophysical impairment, the aesthetic damage continues to generate controversy because it can be objectified but with an important ‘subjective’ component, not only from the injured person but also from the expert in charge of the assessment. Law 35/2015 for the modification of the system for the assessment remains faithful to the use rules for the scale contained in the Royal Decree 8/2004, but for the first time it is introduced a series of factors which should be taken into account for the evaluation (visibility, attraction, reaction and interpersonal relationship alteration), as well as examples for each grade of injury, with the aim of developing a better qualification and quantification of this injury (AU)

Molecular epidemiology suggests Venezuela as the origin of the dengue outbreak in Madeira, Portugal in 2012-2013.

An explosive epidemic occurred in Madeira Island (Portugal) from October 2012 to February 2013. Published data showed that dengue virus type 1 introduced from South America was the incriminated virus. We aim to determine the origin of the strain introduced to Madeira by travellers returning to Europe. Using phylogeographic analysis and complete envelope sequences we have demonstrated that the most probable origin of the strain is Venezuela.

Cases of chikungunya virus infection in travellers returning to Spain from Haiti or Dominican Republic, April-June 2014.

Ten cases of chikungunya were diagnosed in Spanish travellers returning from Haiti (n=2), the Dominican Republic (n=7) or from both countries (n=1) between April and June 2014. These cases remind clinicians to consider chikungunya in European travellers presenting with febrile illness and arthralgia, who are returning from the Caribbean region and Central America, particularly from Haiti and the Dominican Republic. The presence of Aedes albopictus together with viraemic patients could potentially lead to autochthonous transmission of chikungunya virus in southern Europe.

Introduction of an interdisciplinary heart team-based transcatheter aortic valve implantation programme: short and mid-term outcomes.

BACKGROUND: Transcatheter aortic valve implantation (TAVI) has been developed to treat symptomatic aortic stenosis in patients deemed too high risk for open-heart surgery. To address this complex population, an interdisciplinary heart team approach was proposed. AIM: Present the short- and mid-term outcomes of the first 100 patients in the Royal Prince Alfred Hospital multidisciplinary TAVI programme. METHODS: Single-centre registry. Baseline and procedural data were prospectively recorded. Outcomes were recorded according to Valve Academic Research Consortium - version 2 guidelines. RESULTS: All patients underwent a comprehensive interdisciplinary pre-procedural evaluation. Sixty-eight transfemoral and 32 transapical implantations were performed. Mean age was 82 (±8.9) years old with an average logistic EuroSCORE of 33. Although 13 procedures had major complications, there was no intraprocedural mortality. During the first month, 9% of patients were re-admitted due to heart failure and 13% had a permanent pacemaker implanted. A 3% 30-day and 8% follow-up (mean 17 months) mortalities were recorded. While no significant differences in the rate of complications were found between the first and second half of the experience, all cases of mortality within 30 days (n = 3) occurred in the initial half. Sustained haemodynamic results were obtained with TAVI (immediate mean aortic valve gradient reduction from 47 to 9 mmHg; 1-year echocardiographic gradient 9.9 mmHg, with no moderate or severe aortic regurgitation). CONCLUSION: Excellent results can be achieved with TAVI in very high-risk patients at an Australian institution. A comprehensive evaluation based on a heart team can overcome most of the difficulties imposed by this challenging population.

Experiencia de una unidad monográfica de tuberculosis: primeros 500 casos / Experience of a Monographic Tuberculosis Unit: The First 500 Cases

Introducción: La tuberculosis (TB) continúa siendo una enfermedad muy prevalente aunque desde el año 2002 el número de casos anuales muestra una tendencia decreciente en el mundo y también en nuestro país, donde la incidencia es muy variable entre comunidades autónomas. El objetivo principal de este estudio es describir la experiencia de una unidad monográfica de TB de un centro hospitalario de segundo nivel. Pacientes y métodos: Estudio descriptivo de los casos de TB diagnosticados en una unidad monográfica de un hospital secundario entre 2003 y 2011. Se recogieron datos demográficos, clínicos, epidemiológicos y microbiológicos para su análisis. Resultados: Se analizaron 500 casos de TB, encontrando una incidencia anual creciente en todos los subgrupos, incluyendo población autóctona e inmigrante. La mayoría (63,8%) eran varones, con una mediana de edad de 36 años (rango 8 meses-90 años). Un 39,8% de los pacientes era inmigrante. En un 11% de los casos existía coinfección con el virus de la inmunodeficiencia humana. La localización fue pulmonar en el 63,8% de los casos. La letalidad global fue del 5,8% sin encontrar diferencias significativas entre subgrupos (incluyendo población inmigrante y personas infectadas por el virus de la inmunodeficiencia humana). Conclusiones: A pesar de la tendencia descendente global en cuanto al número de casos de TB declarados, en nuestra serie esta es creciente en todos los subgrupos. La existencia de una unidad monográfica de TB junto con un exhaustivo programa de estudio de contactos podría explicar este hallazgo (AU)

Introduction: Tuberculosis (TB) remains a highly prevalent and potentially severe disease. However, since 2002 the annual incidence has been decreasing both worldwide and in Spain, where the incidence varies widely between regions. The main objective of this study is to describe the experience of a monographic TB unit in a second level hospital. Patients and methods: A descriptive study was carried out which included all cases of TB diagnosed in a monographic unit of a secondary hospital between 2003 and 2011. Demographic, clinical, epidemiological and microbiological data were recorded. Results: We analyzed 500 TB cases and found an increasing annual incidence in all subgroups, including native and immigrant populations. Most cases (63.8%) were male, with a median age of 36 years (range 8 months–90 years). In total, 39.8% of patients were foreign born. Coinfection with human immunodeficiency virus (HIV) was found in 11.0% of cases. The pulmonary form was most frequently diagnosed (63.8%). Overall mortality was 5.8% with no significant differences between groups (including foreign born and HIV positive patients). Conclusions: Although TB incidence is globally decreasing, in our study we found an increasing number of cases in recent years in all subgroups, which can be explained by this being a monographic unit with an intensive contact tracing program (AU)

Enzymes involved in l-lactate metabolism in humans.

l-lactate formation occurs via the reduction of pyruvate catalyzed by lactate dehydrogenase. l-lactate removal takes place via its oxidation into pyruvate, which may be oxidized or converted into glucose. Pyruvate oxidation involves the cooperative effort of pyruvate dehydrogenase, the tricarboxylic acid cycle, and the mitochondrial respiratory chain. Enzymes of the gluconeogenesis pathway sequentially convert pyruvate into glucose. In addition, pyruvate may undergo reversible transamination to alanine by alanine aminotransferase. Enzymes involved in l-lactate metabolism are crucial to diabetes pathophysiology and therapy. Elevated plasma alanine aminotransferase concentration has been associated with insulin resistance. Polymorphisms in the G6PC2 gene have been associated with fasting glucose concentration and insulin secretion. In diabetes patients, pyruvate dehydrogenase is down-regulated and the activity of pyruvate carboxylase is diminished in the pancreatic islets. Inhibitors of fructose 1,6-bisphosphatase are being investigated as potential therapy for type 2 diabetes. In addition, enzymes implicated in l-lactate metabolism have revealed to be important in cancer cell homeostasis. Many human tumors have higher LDH5 levels than normal tissues. The LDHC gene is expressed in a broad range of tumors. The activation of PDH is a potential mediator in the body response that protects against cancer and PDH activation has been observed to reduce glioblastoma growth. The expression of PDK1 may serve as a biomarker of poor prognosis in gastric cancer. Mitochondrial DNA mutations have been detected in a number of human cancers. Genes encoding succinate dehydrogenase have tumor suppressor functions and consequently mutations in these genes may cause a variety of tumors.

Experience of a monographic tuberculosis unit: the first 500 cases.

INTRODUCTION: Tuberculosis (TB) remains a highly prevalent and potentially severe disease. However, since 2002 the annual incidence has been decreasing both worldwide and in Spain, where the incidence varies widely between regions. The main objective of this study is to describe the experience of a monographic TB unit in a second level hospital. PATIENTS AND METHODS: A descriptive study was carried out which included all cases of TB diagnosed in a monographic unit of a secondary hospital between 2003 and 2011. Demographic, clinical, epidemiological and microbiological data were recorded. RESULTS: We analyzed 500 TB cases and found an increasing annual incidence in all subgroups, including native and immigrant populations. Most cases (63.8%) were male, with a median age of 36 years (range 8 months-90 years). In total, 39.8% of patients were foreign born. Coinfection with human immunodeficiency virus was found in 11% of cases. The pulmonary form was most frequently diagnosed (63.8%). Overall mortality was 5.8% with no significant differences between groups (including foreign born and human immunodeficiency virus positive patients). CONCLUSIONS: Although TB incidence is globally decreasing, in our study we found an increasing number of cases in recent years in all subgroups, which can be explained by this being a monographic unit with an intensive contact tracing program.