Evaluation of the Stability of Newborn Hospital Parenteral Nutrition Solutions.

(1) Background: parenteral nutrition (PN) solutions are an extremely complex mixture. It is composed of a multitude of chemical elements that can give rise to a large number of interactions that condition its stability and safety. The aim of this study was to evaluate the stability of PN solutions for preterm infants. (2) Methods: eight samples were prepared according to the protocol for prescribing PN in preterm infants. Samples PN1-PN7 had the normal progression of macronutrients and standard amounts of micronutrients for a 1 kg preterm infant. The PN8 sample had a high concentration of electrolytes, with the idea of forcing stability limits. Samples were stored both at room temperature and under refrigeration. Measurements of globule size, pH, density, and viscosity were performed in both storage protocols on different days after processing. (3) Results: the changes in the composition of the samples did not affect the evolution of the stability at the different measurement times and temperatures. Viscosity was affected by the compositional changes made in the PN samples, but no alterations due to time or temperature were observed. Density and pH remained stable, without significant changes due to time, storage temperature, or different composition. (4) Conclusion: all samples remained stable during the study period and did not undergo significant alterations due to compositional changes or different experimental conditions.

Electron Microscopy for the Stability Assessment of Parenteral Nutrition Admixtures: Focus on Precipitation.

(1) Background: parenteral nutrition (PN) is indispensable for patients unable to receive oral or enteral feeding. However, the complexity of PN solutions presents challenges regarding stability and compatibility. Precipitation reactions may occur. The most frequent is the formation of calcium phosphate (Ca-P). The different factors influencing these reactions must be considered to ensure patient safety. (2) Methods: eight paediatric PN solutions were prepared, following standard protocols. Samples were stored at room temperature and in a refrigerator. Electron microscopy, coupled with energy dispersive X-ray spectroscopy (EDS), was employed. Precipitates were analysed for composition and morphology. (3) Results: precipitates were observed in all samples, even at day 0. Crystalline structures, predominantly composed of calcium or magnesium, sometimes associated with chlorine or phosphorus, were detected. Additionally, amorphous precipitates, contained heterogeneous compositions, including unexpected elements, were identified. (4) Conclusions: various precipitates, primarily calcium- or magnesium-based, can form in PN solutions, although it is not expected that they can form under the real conditions of use. Calcium oxalate precipitation has been characterised, but the use of organic calcium and phosphate salts appears to mitigate calcium phosphate precipitation. Electron microscopy provides interesting results on NP precipitation, but sample preparation may present technical limitations that affect the interpretation of the results.

Identification of new targets for glioblastoma therapy based on a DNA expression microarray.

This study provides a comprehensive perspective on the deregulated pathways and impaired biological functions prevalent in human glioblastoma (GBM). In order to characterize differences in gene expression between individuals diagnosed with GBM and healthy brain tissue, we have designed and manufactured a specific, custom DNA microarray. The results obtained from differential gene expression analysis were validated by RT-qPCR. The datasets obtained from the analysis of common differential expressed genes in our cohort of patients were used to generate protein-protein interaction networks of functionally enriched genes and their biological functions. This network analysis, let us to identify 16 genes that exhibited either up-regulation (CDK4, MYC, FOXM1, FN1, E2F7, HDAC1, TNC, LAMC1, EIF4EBP1 and ITGB3) or down-regulation (PRKACB, MEF2C, CAMK2B, MAPK3, MAP2K1 and PENK) in all GBM patients. Further investigation of these genes and enriched pathways uncovered in this investigation promises to serve as a foundational step in advancing our comprehension of the molecular mechanisms underpinning GBM pathogenesis. Consequently, the present work emphasizes the critical role that the unveiled molecular pathways likely play in shaping innovative therapeutic approaches for GBM management. We finally proposed in this study a list of compounds that target hub of GBM-related genes, some of which are already in clinical use, underscoring the potential of those genes as targets for GBM treatment.

Physicochemical Stability of Hospital Parenteral Nutrition Solutions: Effect of Changes in Composition and Storage Protocol.

(1) Background: Parenteral nutrition (PN) is a technique used for the administration of nutrients to patients for whom traditional routes cannot be used. It is performed using solutions with extremely complex compositions, which can give rise to a large number of interactions. These interactions can impact their stability and put the patient's life at risk. The aim of this study is to determine how changes in composition and storage protocol affect the stability of NP solutions. (2) Methods: Twenty-three samples were prepared according to routine clinical practice, with modifications to the concentration of some components. The samples were stored at room temperature (RT) and refrigerated (4 °C). Measurements of the droplet diameter, pH, density and viscosity were performed for both storage protocols on days 1, 3, 10 and 14. (3) Results: The samples with the lowest concentration of lipids (PN13-17) and proteins (PN18-22) showed a larger droplet diameter than the rest of the samples throughout the experiments. The USP limits were exceeded for some of the measurements of these sample groups. The pH density and viscosity remained relatively constant under the conditions studied. (4) Conclusions: The PN samples were considered stable and safe for administration under real-world conditions, but the samples with the lowest concentrations of lipids and proteins showed a tendency towards emulsion instability.

Discovery of recessive effect of human polymerase δ proofreading deficiency through mutational analysis of POLD1-mutated normal and cancer cells.

Constitutional heterozygous pathogenic variants in the exonuclease domain of POLE and POLD1, which affect the proofreading activity of the corresponding polymerases, cause a cancer predisposition syndrome characterized by increased risk of gastrointestinal polyposis, colorectal cancer, endometrial cancer and other tumor types. The generally accepted explanation for the connection between the disruption of the proofreading activity of polymerases epsilon and delta and cancer development is through an increase in the somatic mutation rate. Here we studied an extended family with multiple members heterozygous for the pathogenic POLD1 variant c.1421T>C p.(Leu474Pro), which segregates with the polyposis and cancer phenotypes. Through the analysis of mutational patterns of patient-derived fibroblasts colonies and de novo mutations obtained by parent-offspring comparisons, we concluded that heterozygous POLD1 L474P just subtly increases the somatic and germline mutation burden. In contrast, tumors developed in individuals with a heterozygous mutation in the exonuclease domain of POLD1, including L474P, have an extremely high mutation rate (>100 mut/Mb) associated with signature SBS10d. We solved this contradiction through the observation that tumorigenesis involves somatic inactivation of the wildtype POLD1 allele. These results imply that exonuclease deficiency of polymerase delta has a recessive effect on mutation rate.

The In Vitro Inhibitory Activity of Pacaya Palm Rachis versus Dipeptidyl Peptidase-IV, Angiotensin-Converting Enzyme, α-Glucosidase and α-Amylase.

The pacaya palm (Chamaedorea tepejilote Liebm) is an important food that is commonly consumed in Mexico and Central America due to its nutritive value. It is also used as a nutraceutical food against some chronic diseases, such as hypertension and hyperglycemia. However, few reports have indicated its possible potential. For this reason, the goal of this research was to evaluate the effects of the enzymatic activity of the pacaya palm inflorescence rachis on both hypertension and hyperglycemia and the effects of thermal treatments on the enzymatic activity. The enzymatic inhibition of ACE (angiotensin-converting enzyme), DPP-IV (dipeptidyl peptidase-IV), α-glucosidase and α-amylase were evaluated, all with powder extracts of pacaya palm inflorescences rachis. The results indicated that thermally treated rachis showed increased enzymatic inhibitory activity against α-amylase and DPP-IV. However, all rachis, both with and without thermal treatment, showed low- or no enzymatic activity against α-glucosidase and ACE. Apparently, the mechanism of action of the antidiabetic effect of rachis is mediated by the inhibition of α-amylase and DPP-IV and does not contribute with a significant effect on enzymes involved in the hypertension mechanism. Finally, the properties of the extract were modified via the extraction method and the temperature tested.

Genetic and clinical characterization of a novel FH founder mutation in families with hereditary leiomyomatosis and renal cell cancer syndrome.

BACKGROUND: Hereditary leiomyomatosis and renal cell cancer syndrome is a rare autosomal dominant hereditary syndrome. Previously, we published the largest cohort of FH mutation carriers in Spain and observed a highly recurrent missense heterozygous variant, FH(NM_000143.4):c.1118A > G p.(Asn373Ser), in 104 individuals from 31 apparently unrelated families. Here, we aimed to establish its founder effect and characterize the associated clinical phenotype. RESULTS: Haplotype analysis confirmed that families shared a common haplotype (32/38 markers) spanning 0.61-0.82 Mb, indicating this recurrent variant was inherited from a founder ancestor. Cutaneous and uterine leiomyomatosis were diagnosed in 64.6% (64/99) and 98% (50/51) of patients, respectively, and renal cell cancer was present in 10.4% (10/96). The pathogenic FH_c.1118A > G variant is a Spanish founder mutation that originated 12-26 generations ago. We estimate that the variant may have appeared between 1370 and 1720. Individuals carrying this founder mutation had similar frequency of renal cell cancer and a higher frequency of renal cysts and leiomyomas than those in other cohorts of this syndrome. CONCLUSIONS: In the Spanish province of Alicante there is a high prevalence of HLRCC because of the founder mutation FH c.1118A > G; p.(Asn373Ser). The characterization of founder mutations provides accurate and specific information regarding their penetrance and expressivity. In individuals with suspected HLRCC from the province of Alicante, genetic testing by direct analysis of the founder FH c.1118A > G; p.(Asn373Ser) mutation may be a faster and more efficient diagnostic tool compared with complete gene sequencing.

Intoxicación aguda por piretroides: reporte de caso / ACUTE PYRETHROID POISONING: CASE REPORT

Paciente masculino de 21 años de edad, procedente y residente de la provincia de Chulumani, acudió al servicio de Emergencias del Hospital de Chulumani tras la ingesta accidental de insecticida que tenía como principal componente "cipermetrina" que es un piretroide sintético, presento paro respiratorio rápidamente, asociado a deterioro de estado de conciencia por lo que fue intubado y requirió asistencia ventilatoria mecánica, y posteriormente transferido a la Unidad de Terapia Intensiva del Hospital Juan XXIII del departamento de La Paz, tras su internación se pudo evidenciar las características clínicas propias de intoxicación por piretroides, que no es una entidad común en nuestro medio, entre los síntomas presentes en el paciente encontramos: deterioro de estado de conciencia, pupilas puntiformes, fasciculaciones fasciales, temblores e hiperexcitabilidad en extremidades superiores e inferiores frente a estímulos externos, hipotermia, sialorrea, diaforesis profusa y persistente, bradicardia, diarrea y debilidad proximal de extremidades con perdida de la fuerza muscular, lo que llevo a una estadía prolongada en la UTI, destete prolongado y fracaso de extubación en una oportunidad. Se logró el retiro definitivo de ventilador mecánico después de 20 días de internación e intubación. Ante síntomas semejantes a la intoxicación por organofosforado recibió tratamiento en base a atropina y medidas de soporte vital propias de la Unidad de Terapia Intensiva, optimizando la rehabilitación integral y respiratoria del paciente.

A 21-years-old male patient, dweller from Chulumani province, went to the Hospital of Chulumani Emergency Service after accidental intake of cypermethrin which is a synthetic pyrethroid insecticide. Patient presented respiratory arrest associated to deterioration of his state of consciousness, intubation and mechanical ventilation was performed. Subsequently, patient was transferred to the intensive care unit of Hospital Juan XXIII in La Paz city. After hospital admission, clinical proper characteristics of a pyrethroid intoxication, which is not a common entity in our environment, were observed. Signs such as deterioration in the state of consciousness, pinpoint pupils, fascial fasciculation, tremors and hyperexcitability in upper and lower limbs to external stimuli, hypothermia, sialorrhea, profuse and persistent diaphoresis, bradycardia, diarrhea and proximal weakness of limbs with loss of muscle strength were evidenced. This leaded to patient's prolonged staying in ICU and weaning as well as extubation failure at an opportunity. Definitive removal of mechanical ventilator was achieved after 20 days of hospitalization and intubation. Given symptoms similar to organophosphate poisoning patient received a treatment based on atropine and life support measures of the Intensive Care Unit, optimizing in this way patient's respiratory and integral rehabilitation.

Attitudes towards physician-assisted suicide and euthanasia in Spanish university students / Actitudes hacia la eutanasia y el suicidio medicamente asistido en estudiantes universitarios españoles / Atitudes em relação a eutanásia e suicídio medicamente assistido em estudantes universitários espanhóis

Abstract Attitudes toward physician-assisted death among medical students differ between populations. The aim of this study was to explore attitudes towards euthanasia and physician-assisted suicide among Spanish university students. A cross-sectional survey was conducted by asking undergraduate students (Medicine, Nursing and Law) of the University of Santiago de Compostela to complete an anonymous 17-item questionnaire. Most participants exhibited a positive attitude towards physician-assisted suicide (54%) and euthanasia (75%), as well as towards their legalization. Attitudes were consistent with the underlying ethical reasoning, with no differences in terms of age, gender or academic degree. In addition, consistency was found between attitudes and willingness to participate in physician-assisted suicide and euthanasia, should they be legal. The results showed that the attitudes of medical students towards euthanasia and physician-assisted suicide were positive and similar to non-medical students.

Resumen La actitud de los estudiantes de Medicina ante a la muerte médicamente asistida difiere entre poblaciones. El objetivo de este estudio ha sido explorar las actitudes hacia la eutanasia y el suicidio médicamente asistido en estudiantes universitarios españoles. Se realizó una encuesta transversal en estudiantes de grado (Medicina, Enfermería y Derecho) de la Universidad de Santiago de Compostela que completaron un cuestionario anónimo de 17 preguntas. La mayoría de los participantes mostraron una actitud positiva hacia el suicidio médicamente asistido (54%) y la eutanasia (75%), así como hacia su legalización. Las actitudes fueron coherentes con los argumentos éticos, no encontrando diferencias en relación con la edad, el sexo o la titulación. Asimismo, las actitudes estaban de acuerdo con la intención de participar en estos procedimientos, si fueran legales. Los resultados muestran que la actitud de los estudiantes de medicina hacia la eutanasia y el suicidio asistido es positiva y similar a la de estudiantes de enfermería y derecho.

Resumo A atitude dos estudantes de medicina ante a morte medicamente assistida difere entre populações. O objetivo deste estudo foi explorar as atitudes para a eutanásia e o suicídio medicamente assistido em estudantes universitários espanhóis. Foi realizada uma pesquisa transversal em estudantes de graduação (medicina, enfermagem e direito) da Universidade de Santiago de Compostela que completaram um questionário anônimo de 17 perguntas. A maioria dos participantes mostrou atitude positiva para o suicídio medicamente assistido (54%) e a eutanásia (75%), bem como para a sua legalização. As atitudes foram coerentes com os argumentos éticos, não encontrando diferenças em relação a idade, sexo ou titulação. Assim mesmo, as atitudes estavam de acordo com a intenção de participar nestes procedimentos, se fossem legais. Os resultados mostram que a atitude dos estudantes de medicina para a eutanásia e o suicídio assistido é positiva e similar à de estudantes de enfermagem e direito.

Cell-free circulating tumor DNA in colorectal cancer: a proof of concept with simplified methodology

BackgroundCell-free DNA analysis (cfDNA) holds promise for residual disease or tumor burden quantification in colorectal cancer, with reduced costs and diagnostic equipment compared to gold standard-specific tumor DNA (ctDNA) analysis.MethodsThis prospective case–control study included 46 colorectal cancer patients and healthy controls to perform cfDNA quantification by fluorometry using Quantus Fluorometer (Promega, Madison, WI) and using cell-free DNA ScreenTape assay (Agilent) and 4200 TapeStation instrument (Agilent Technologies, Inc., Santa Clara, CA, USA). cfDNA quantification results were correlated with stage, clinical and histopathological features.Results33 localized (8 stage I, 12 stage II, and 13 stage III) and 13 advanced colorectal cancer patients were included. No differences in cfDNA quantification by fluorometry were demonstrated depending on stage or histopathological features in localized disease patients. Differences in cfDNA quantification by fluorometry could be demonstrated in patients with advanced disease depending on the presence of liver metastases and synchronous or metachronous metastatic disease. Differences in cfDNA quantification by fluorometry could be demonstrated between advanced colorectal cancer patients and both localized disease patients and healthy controls. Secondary cfDNA analysis by electrophoresis, although showing more specificity to measure ctDNA in cfDNA values, could not improve the capacity to detect differences between analyzed a groups beyond previously achieved with fluorometry.ConclusionThis exploratory analysis of cfDNA based on fluorometry and electrophoresis methods showed promising results discriminating colorectal cancer and non-cancer patients, as well as different colorectal cancer stages and disease profiles. Further studies are needed to increase our knowledge and to help to overcome barriers to broader implementation and applications. (AU)

Indices de perfusión y poder mecánico en COVID 19 a muy alta altitud / Indices de perfusión y poder mecánico en COVID 19 a muy alta altitud

Introducción: En diciembre de 2019, la ciudad de Wuhan en la provincia de Hubei en China se convirtió en el centro de un brote de neumonía atípica, el 11 de marzo del 2020, la Organización Mundial de Salud la declaró como Pandemia. El objetivo es describir los índices de perfusión y el poder mecánico en pacientes atendidos a muy alta altitud.

Delirium en la Unidad de Terapia Intensiva: Diagnóstico preco y oportuno ¿lo hacemos? / Delirium in the Intensive Care Unit: Early and timely diagnosis, shall we do it?

El desarrollo de la Medicina Critica y la proliferación de las áreas de Terapia Intensiva han mejorado el pronóstico y la evolución del enfermo critico grave. Sin embargo, los problemas psiquiátricos como el delirium no son lo suficientemente conocidos incluso por el médico intensivista, por lo que no es oportunamente diagnosticado y tratado, siendo de esta manera un factor que podría incrementar la estadía de los pacientes en la Unidad de Terapia Intensiva e incluso la mortalidad. Conclusiones: El delirium es un síndrome frecuente en la Unidad de Terapia Intensiva del Instituto Nacional de Tórax, además es un síndrome subdiagnosticado por la falta de aplicación de instrumentos de evaluación de este síndrome. El delirium puede presentarse a cualquier edad, en los pacientes críticos internados en las Unidades de Terapia Intensiva. Es de origen multifactorial prevenible y tratable.

Megacolon Toxico y Colitis seudomembranos a: reporte de caso / Toxic Megacolon and Pseudomembrane Colitis a: Case Report

La colitis pseudomembranosa es una patología relacionada con el uso de antibióticos. En raras ocasiones, evoluciona a megacolon tóxico que podría recurrir resolución quirúrgica. Se presenta el caso de una mujer de 77 años, que recibió antibioticoterapia de amplio espectro unos días antes de la consulta. Presente diarrea, fiebre y vómitos. Radiografía computarizada de abdomen distensión de colon derecho.

Influenza A (h1n1): Un resumen de lecciones aprendidas / Influenza A (h1n1): A summary of lessons learned

A finales de marzo de 2009 fue aislado un nuevo virus influenza A (H1N1) de origen porcino, diseminándose inicialmente por México y EE.UU., y después internacionalmente. Varios estudios realizados en animales demostraron que esta nueva mutación viral posee una mayor morbimortalidad que el virus de la influenza estacional. Su transmisibilidad es ligeramente superior a la de la gripe estacional, y equivalente a la de las anteriores pandemias. Su patogenicidad y virulencia son bajas. El cuadro clínico es similar al típico de la gripe estacional, con curación espontánea, si bien el espectro clínico es extenso, pues va desde casos asintomáticos hasta neumonía grave o mortal. La población afectada ha sido predominantemente joven, de menos de 30 años. Menos de la mitad de los pacientes hospitalizados en EE.UU. y de los casos mortales en México presentaban enfermedades crónicas o procesos de base concomitantes. Un hecho descrito y preocupante fue la sobreinfección bacteriana pulmonar; la que oscilo desde el 4 al 29 % en los casos severos que resultaron en hospitalización o muerte en los Estados Unidos, Argentina, Australia y Nueva Zelanda. Para la prevención y control de la infección, a través de la reducción de susceptibles, se ha dispuesto el uso de una vacuna monovalente específica contra el virus. Finalmente, se debe tener en cuenta que los conocimientos acerca de la infección por el virus de influenza A (H1N1) se modifican en forma permanente por lo cual es muy probable que el presente documento deba ser actualizado en el futuro.

ABSTRACT In late March 2009 was isolated a new virus influenza A (H1N1) of swine origin, spreading from Mexico and the U.S. initially, and then internationally. Studies in animals have shown that this new virus mutation has a higher morbidity than the seasonal flu virus. Its transmissibility is slightly higher than seasonal flu, and equivalent to that of previous pandemics. Pathogenicity and virulence are low. The clinical picture is similar to the typical seasonal flu, with spontaneous recovery, although the clinical spectrum is broad, as itgoes from asymptomatic to severe or fatal pneumonia. The affected population is predominantly young, less than 30 years. Less than half of hospitalized patients in the U.S. and fatal cases in Mexico had chronic diseases or concomitant underlying processes. A disturbing fact was described and pulmonary bacterial superinfection, which ranged from 4 to 29% in severe cases resulting in hospitalization or death in the United States, Argentina, Australia and New Zealand. For prevention and infection control through the reduction of susceptibles, is arranged use of a specific monovalent vaccine against the virus.

Soporte nutricional en el paciente séptico: ¿cual es el rol de la inmunonutriciión con glutamina en los pacientes postoperados de sepsis abdominal? / Nutritional sppoort in the septic patient: what is the role of immunonutrition with glutamine in patients after abdominal sepsis?

Objetivo: Evaluar el efecto de la administración de glutamina asociada a la nutrición parenteral total (NPT) y/o nutrición parenteral complementaria (NPC), en pacientes que cursan con sepsis abdominal resuelto quirúrgicamente (qx), sobre la morbimortalidad a corto plazo. Materiales y métodos: Se llevo a cabo un ensayo clínico controlado aleatorizado doble ciego en las UTI del Hospital Municipal Boliviano Holandés (HMBH), Instituto Gastroenterológico Boliviano-Japonés (IGBJ) y la Corporación del Seguro Social Militar (COSSMIL). Se seleccionaron 216 pacientes con sepsis abdominal (sepsis, sepsis severa y choque séptico) que requirieron tratamiento quirúrgico y tratados en su postoperatorio en las UTI de los hospitales mencionados. Luego de 72h del acto quirúrgico, se inició la nutrición parenteral total (NPT) o nutrición parenteral complementaria (NPC) en dos grupos: el primero: NPT/NPC complementado con glutamina y en el segundo solo con NPT/NPC estándar. El día1 y el 3 del postoperatorio se midieron los niveles NUU, el APACHE II, las complicaciones infecciosas y no infecciosas asociadas, el balance nitrogenado y la duración de la estancia hospitalaria. Resultados: No se encontraron diferencias estadísticamente significativas en ninguno de los parámetros medidos entre el grupo de glutamina (GGLUT) y el grupo no glutamina (GNGLUT). Sin embargo, en un subanálisis del GGLUT se encontró una diferencia importante en el valor de APACHE II entre el primer día y el tercero (P < 0.05). Con respecto a la mortalidad, ésta fue similar en ambos grupos, encontrándose alrededor del 10% a los 30 días. Conclusión: La NPT o NPC temprana suplementada con glutamina no presenta diferencias tempranas en cuanto a la respuesta metabólica al trauma, el estado nutricional previo, ni el hipercatabolismo proteico. Sin embargo, ésta se asocia aparentemente a menor severidad del cuadro séptico de base.

Objective: To evaluate the effect of glutamine administration associated with total parenteral nutrition (TPN) and / or supplemental parenteral nutrition (NPC), in patients presenting with abdominal sepsis resolved surgically (qx), on short-term morbidity. Materials and methods: We conducted a randomized double-blind randomized controlled trial in the ICU ofthe Hospital Municipal Boliviano Dutch (HMBH), Bolivian-Japanese Gastroenterological Institute (IGBJ) and the Military Social Security Corporation (COSSMIL). We selected 216 patients with abdominal sepsis (sepsis, severe sepsis and septic shock) that needed surgery and postoperatively treated in ICUs of hospitals mentioned. After 72 hours of surgery, started total parenteral nutrition (TPN) or supplemental parenteral nutrition (NPC) in two groups: the first: NPT / NPC supplemented with glutamine and second only to NPT / standard NPC. On day 1 and 3 after surgery NUU levels were measured, the APACHE II, the infectious and noninfectious complications associated nitrogen balance and the length of hospital stay. Results: No statisticallysignificant differences were foundin anyoftheparameters measured between the glutamine group (GGLUT) and no glutamine group (GNGLUT). However, in a subanalysis of GGLUT found a significant difference in the value of APACHE II between the first day and the third (P <0.05). With respect to mortality, it was similar in both groups, being about 10% at 30 days. Conclusion: The early NPC NPT or supplemented with glutamine no differences in terms of early metabolic response to trauma, nutritional status prior nor hypercatabolism protein. However, this is associated apparently less severe septic box base.

Documento de consenso sobre la implementación de la secuenciación masiva de nueva generación en el diagnóstico genético de la predisposición hereditaria al cáncer / Consensus document on the implementation of next generation sequencing in the genetic diagnosis of hereditary cancer

El diagnóstico genético de los síndromes de cáncer hereditario ofrece la oportunidad de establecer unas medidas de predicción/prevención eficaces en el paciente y sus familiares que se traducen en una disminución de la morbimortalidad por cáncer en las familias de alto riesgo genético. La secuenciación masiva (NGS) ofrece una considerable mejora de la eficiencia del diagnóstico genético, permitiendo un aumento del rendimiento diagnóstico con una reducción sustancial del tiempo de respuesta y costes económicos. En consecuencia, la implementación de esta nueva tecnología es una gran oportunidad de mejora en el manejo clínico de las familias afectas. El objetivo de la presente guía es establecer un marco de recomendaciones útiles para una implementación planificada y controlada de la NGS en el contexto de la predisposición hereditaria a cáncer, que permita potenciar las fortalezas y oportunidades que ofrece dicha tecnología y minimizar las debilidades y amenazas que puedan derivarse de su uso. Está inspirada en las recomendaciones de sociedades internacionales, habiendo sido adaptada a nuestro entorno, y teniendo en cuenta aspectos coyunturales a nivel organizativo y biojurídico. Se aportan 41 declaraciones agrupadas en 6 apartados: utilidad clínica y diagnóstica, consentimiento informado y asesoramiento genético pretest y postest, validación de los procedimientos analíticos, informe de resultados, gestión de la información y distinción entre ámbito de investigación y ámbito asistencial. Esta guía ha sido elaborada por la Asociación Española de Genética Humana (AEGH), la Sociedad Española de Medicina de Laboratorio (SEQC-ML) y la Sociedad Española de Oncología Médica (SEOM)

Genetic diagnosis of hereditary cancer syndromes offers the opportunity to establish more effective predictive and preventive measures for the patient and their families. The ultimate objective is to decrease cancer morbidity and mortality in high genetic risk families. Next Generation Sequencing (NGS) offers an important improvement in the efficiency of genetic diagnosis, allowing an increase in diagnostic yield with a substantial reduction in response times and economic costs. Consequently, the implementation of this new technology is a great opportunity for improvement in the clinical management of affected families. The aim of these guidelines is to establish a framework of useful recommendations for planned and controlled implementation of NGS in the context of hereditary cancer. These will help to consolidate the strengths and opportunities offered by this technology, and minimise the weaknesses and threats which may derive from its use. The recommendations of international societies have been adapted to our environment, taking the Spanish context into account at organisational and juridical levels. Forty-one statements are grouped under six headings: clinical and diagnostic utility, informed consent and genetic counselling pre-test and post-test, validation of analytical procedures, results report, management of information and distinction between research and clinical context. This guide has been developed by the Spanish Association of Human Genetics (AEGH), the Spanish Society of Laboratory Medicine (SEQC-ML) and the Spanish Society of Medical Oncology (SEOM)

Errores diagnósticos en el accidente vascular cerebral / Diagnostc errorss in stroke

El Accidente Vascular Cerebral (AVC) es la tercera causa de muerte y la primera de discapacidad en muchos países desarrollados, afectando principalmente a adultos de mediana edad y ancianos. Sin embargo en nuestro medio no existen publicaciones que muestren la prevalencia de esta enfermedad. Objetivo del estudio: El presente estudio tiene como objetivo establecer la prevalencia de los Falsos AVC (FAVC), en pacientes atendidos en los servicios de emergencias (SE), neurología y terapia intensiva del Hospital de clínicas e Instituto Nacional de Tórax (INT). Material y métodos: Estudio transversal descriptivo de todos los casos diagnosticados de AVC durante doce meses consecutivos (enero a diciembre de 2009), en el servicio de emergencias, neurología del Hospital de Clínicas y Unidad de terapia Intensiva del INT, La Paz-Bolivia. La información se obtuvo mediante la revisión de expedientes clínicos. Criterios de inclusión: pacientes con diagnósticos de AVC isquémico, AVC hemorrágico, y Accidente isquémico transitorio (AIT), evaluados por neurología/neurocirugía y con diagnóstico dudoso de AVC. Se excluyeron a pacientes con Hemorragia subaracnoídea (HSA), hematomas subdurales y epidurales. Se estableció el diagnostico de FAVC, según los criterios de las guías de la Organización Mundial de Salud (OMS) publicadas el 2005, "WHO STEPS Stroke Manual". Resultados: De enero a diciembre de 2009, se atendieron un total de 385 pacientes con AVC, de los cuales, 110 fueron catalogados como AIT (31%), 191 AVC isquémico (53%) y 57 AVC hemorrágico (16%). Se evidenciaron en 65 historias clínicas FACV, que corresponden a un 18.2% del total de pacientes incluidos en el estudio, edad promedio de 79 años, con mayor prevalencia en mujeres 64.6%. Diagnosticos alternativos más frecuentes: síncope/presíncope (10.8%), síndrome confusional (21.5%), disminución del nivel de conciencia (27.7%), debilidad generalizada (6.2%), crisis epiléptica 6.2%. El 71,7% de los FAVC fueron atribuidos a causas sistémicas. Se realizo TAC de encéfalo en 70.8% de los casos de FAVC. Fueron dados de alta el 27% de todos los AIT, 27% de los AVC isquémicos y 1.7% de los AVC hemorrágicos. Conclusión Podemos afirmar que en los pacientes con enfermedad cerebrovascular aguda, existen errores diagnósticos en un porcentaje considerable. Esto se evidencia principalmente en los servicios de emergencias, donde casi un tercio de todos los casos diagnosticados de AVC y casi la mitad de los diagnósticos de AIT que son dados de alta pueden ser erróneos. La mayor parte de los falsos diagnósticos ocurren en pacientes ancianos con alguna enfermedad sistémica y que no son valorados por neurología y/o neurocirugía.

Cerebral Vascular Accident (CVA) is the third leading cause of death and disability in the first of many developed countries, affecting mostly middle-aged adults and the elderly. However, in our environment do not exist publications that show the prevalence of this disease. Study Objective: This study aims to establish the prevalence of false AVC (FAVC) in patients treated at emergency services (SE), neurology and intensive care clinics Hospital and National Institute of Chest Diseases (INT). Material and methods: Cross-sectional descriptive of all diagnosed cases of AVC for twelve consecutive months (January to December 2009), emergency services, neurology clinics and Hospital Intensive Care Unit of the INT, La Paz, Bolivia. The information was obtained by reviewing medical records. Inclusion criteria: patients with ischemic stroke, hemorrhagic stroke and transient ischemic attack (TIA) evaluated by neurology/neurosurgery and uncertain diagnosis of stroke. We excluded patients with subarachnoid hemorrhage (SAH), subdural and epidural hematomas. A diagnosis ofFAVC according to the criteria ofthe guidelines of the World Health Organization (WHO) published in 2005, "WHO STEPS Stroke Manual". Results: From January to December 2009, attended a total of 385 stroke patients, of whom 110 were classified as TIA (31%), 191 ischemic stroke (53%) and 57 hemorrhagic stroke (16%). Were found in 65 FACV records, corresponding to 18.2% of all patients included in the study, average age 79 years, with higher prevalence in women 64.6%. Most common alternative diagnoses: syncope/presyncope (10.8%), delirium (21.5%), decreased level of consciousness (27.7%), generalized weakness (6.2%), seizures 6.2%. 71.7% ofthe FAVC were attributed to systemic causes. CT brain was performed in 70.8% of cases of FAVC. Were discharged 27% of all AIT, 27% of ischemic stroke and 1.7% of hemorrhagic stroke. Conclusion We can say that in patients with acute cerebrovascular disease, diagnostic errors in a considerable percentage. This is evidenced primarily in the emergency services, where nearly a third of all diagnosed cases of stroke and nearly half of the diagnoses of TIA are discharged can be misleading. Most of the false diagnoses occur in elderly patients with systemic disease and are not valued by neurology and/or neurosurgery.

Enfermedad tromboembólica venosa: ¿una patología frecuente poco reconocida? / Venous thromboembolic disease: a rare pathology?

El tromboembolismo pulmonar (TEP), es el resultado de la obstrucción de la circulación arterial pulmonar por un émbolo procedente en la mayoría de los casos (95%) del sistema venoso profundo de las extremidades inferiores (grandes venas proximales), en menor frecuencia de las pélvicas. Otros orígenes pueden ser: vena cava, cavidades cardíacas derechas, aurícula izquierda (fibrilación auricular), válvulas cardíacas (endocarditis), ventrículo derecho (necrosis) y miembros superiores. Son poco frecuentes los émbolos formados por tumores, aire, fibrina, líquido amniótico, medula ósea y cuerpos extraños. OBJETIVO El objetivo del presente estudio fue determinar la frecuencia y la incidencia de la Trombosis venosa profunda (TVP) diagnosticada en el servicio de Medicina I del Hospital de Clínicas y Unidad de Terapia Intensiva del Instituto Nacional de Tórax, en la ciudad de La Paz - Bolivia. MATERIAL Y MÉTODOS Se incorporaron a la investigación todos los pacientes mayores de 16 años que fueron dados de alta o fallecieron en el servicio de Medicina I del Hospital de Clínicas y la Unidad de Terapia Intensiva del Instituto Nacional de Tórax durante un período de 24 meses, comprendido entre el 1 de junio del 2004 al 30 de junio del 2006 que tenían como diagnósticos de egreso tromboembolismo venoso (TEV), tromboembolia pulmonar (TEP), infarto de pulmón y/o trombosis venosa profunda (TVP). Estos diagnósticos de TEV, de acuerdo a la Clasificación Estadística Internacional de Enfermedades y Problemas Relacionados con la Salud (CIE-10), correspondían a: embolia de pulmón con y sin corazón pulmonar agudo (I-26), flebitis y tromboflebitis (I-80) y tromboflebitis de otros vasos profundos de los miembros inferiores (I-82) RESULTADOS El diagnóstico de TEV se confirmó objetivamente en el 22% de estos enfermos, la relación varón/mujer fue de 1/2. La frecuencia de TEV para el período en estudio fue 0.92%. Los 9 pacientes con el diagnóstico de TEV fueron distribuidos en dos grupos según el momento de aparición del cuadro clínico. 5 pacientes (57.22%) tenían signos y/o síntomas de TEP o TVP cuando ingresaron en los hospitales o los desarrollaron durante los primeros cuatro días de internación, y 4 enfermos (42.77%) los presentaron a partir del quinto día de internación. El 30.98% de los pacientes que desarrollaron una TEV intrahospitalaria tenían indicada profilaxis con ASA durante la internación, aunque no es posible asegurar que ésta se hubiera cumplido en forma correcta. Un paciente (6.62%) con TEV, internado, desarrollo a enfermedad en el curso de un tratamiento anticoagulante adecuado. Seis pacientes (68.07%) tuvieron TVP y 2 (18.67%) TEP. En un paciente (12%) se confirmó la presencia simultánea de TEP y TVP. La mortalidad intrahospitalaria global de los pacientes con TEV, atribuida a la TEV u otras causas, fue 19% (2 pacientes). Los pacientes que ingresaron en los hospitales con el diagnóstico de TEV tuvieron una mortalidad significativamente más baja que la del grupo que desarrolló la enfermedad durante la internación (0.5% vs. 30.98% respectivamente, p=0.004). Aquellos pacientes que por la gravedad del cuadro clínico (n=2) debieron ser internados en unidades de cuidados intensivos tuvieron una mortalidad de 43.75%. La incidencia de TEV fue 0.15%; IC 95%, 0.37 a 0.42 y alcanzó su valor más elevado (0.80%;IC 95%: 0.78% a 0.82%) durante la sexta década de la vida. La incidencia fue mayor en el sexo femenino (88.8%; IC95%: 0.44 a 0.49%). Entre los factores de riesgo identificados en esta población con TEV, clasificados de acuerdo al riesgo relativo indirecto de los mismos. Los más frecuentes fueron: reposo en cama durante más de 3 días y antecedente de TEP o TVP. La frecuencia de presentación de éstos fue diferente según la TEV hubiera sido adquirida en la comunidad o durante la internación, pero solamente el antecedente de TEP o TVP fue significativamente más frecuente en aquellos pacientes que ingresaron al hospital con TEV (p=0.007). CONCLUSIÓN La TEV es una enfermedad que puede prevenirse. No obstante, sólo un tercio de los enfermos que desarrollaron TEV en el Hospital de Clínicas y Unidad de Terapia Intensiva del INT tenían indicado tratamiento o profilaxis con ASA y warfarina.

Pulmonary embolism (PE) is the result of obstruction of the arterial circulation from pulmonary embolus, in most cases (95%), the deep venous system of the lower extremities (large proximal veins) in less frequent the pelvis. Other sources include: vena cava, righ heart, left ventricle (necrosis) and upper limbs. Emboli are rare tumors composed of, air, fibrin, amniotic fluid, bone marrow and foreign bodies. OBJETIVE The aim of this study was to determine the frequency and incidence of venous thrombosis (DVT), objectively diagnosed in the service of Medicine I, University Hospital and Intensive Care Unit, National Institute of Thorax, the city of La Paz-Bolivia. MATERIAL AND METHODS They joined the investigation all patients over 16 who were discharged or died in the service of Medicine I, University Hospital and the Intensive Care Unit, National Institute of chest for a period of 24 months between the 1 June 2004 to June 30, 2006, and had discharge diagnoses as service venous thromboembolism (VTE), pulmonary embolism (PE), acute lung and/or deep vein thrombosis (DVT). These diagnoses ofVTE, according to the International Statistical Classification of Diseases and Related Health Problems (ICD-10), corresponding to: pulmonary embolism with acute pulmonary and cored (I-26), phlebitis and thrombophlebitis (I-80) and trhomboembophlebitis of other deep vessels of lower limbs (I-82). RESULTS The diagnosis of VTE was confirmed objectively in 22% ofthese patients, the male/ female ratio was V2. The frequency of VTE for the study period was 0.92%. The 9 patients with the diagnosis of VTE were divided into two group according to time of onset of symptoms. 5 patients (57.22%) had sings and/or symptoms of DVT or pulmonary embolism when admitted to hospitals or developed during the first four days of hospitalization, and 4 patients (42.77%) presented after the fifth day of hospitalization. The 30.98% ofpatient who developed VTE prophylaxis hospital ASA had indicated during hospitalization, although it is not possible to ensure that it had been performed correctly. One patient (6.62%) with VTE, boarding, development of illness in the course of anticoagulant treatment. Six patient (68.07%) had DVT and 2 (18.67%) TEP. In one patient (12%) confirmed the simultaneous presence of PE and DVT. Overall hospital mortality of patient with VTE attributed to other causes, was 19% (2 patients). Patients admitted to hospital with a diagnosis of VTE had a significantly lower mortality than the group that developed the disease during hospitalization (0.5% vs 30.98% respectively, ) p=0.004. Those patient by severity of symptoms (n=2) had to be hospitalized in intensive care units had a mortality rate of 43.74%. the incidenceof VTE was 0.15%, 95% IC, 0.37 to 0.42 and reached its highest value (0.80%, 95% IC, 0.78% to 0.82%) during the sixth decade oflife. The incidence was higherin females (88.8%, 95% IC 0.44 to 0.49%). Among the identified risk factors for VTE in this population, classified according to the relative risk of them indirect. The most frequent were: bed rest for more than 3 days and history of DVT or pulmonary embolism. The frequency of occurrence of these was different depending on the VTE was acquired in the community or during hospitalization, but only a history of DVT or pulmonary embolism was significantly more frequent in those patients admitted to hospital with VTE (p=0.007). CONCLUSION VTE is a preventable disease. However, only one third of patient developed VTE in the University Hospital and Intensive Care Unit of INT, had indicated treatment or prophylaxis with ASA and warfarin .