SEOM clinical guidelines in advanced and recurrent breast cancer (2018).

Although the metastasic breast cancer is still an incurable disease, recent advances have increased significantly the time to progression and the overall survival. However, too much information has been produced in the last 2 years, so a well-based guideline is a valuable document in treatment decision making. The SEOM guidelines are intended to make evidence-based recommendations on how to manage patients with advanced and recurrent breast cancer to achieve the best patient outcomes based on a rational use of the currently available therapies. To assign a level of certainty and a grade of recommendation the United States Preventive Services Task Force guidelines methodology was selected as reference.

SEOM clinical guidelines in advanced and recurrent breast cancer (2018)

Although the metastasic breast cancer is still an incurable disease, recent advances have increased significantly the time to progression and the overall survival. However, too much information has been produced in the last 2 years, so a well-based guideline is a valuable document in treatment decision making. The SEOM guidelines are intended to make evidence-based recommendations on how to manage patients with advanced and recurrent breast cancer to achieve the best patient outcomes based on a rational use of the currently available therapies. To assign a level of certainty and a grade of recommendation the United States Preventive Services Task Force guidelines methodology was selected as reference

No disponible

Adjuvant regimens with trastuzumab administered for small HER2-positive breast cancer in routine clinical practice

Purpose. Trastuzumab has proven to improve the prognosis of HER2-positive breast cancer, but the information available about its administration for small tumors is still limited. Therefore, we assessed the use of adjuvant regimens with trastuzumab for the treatment of small HER2-positive breast cancer in routine clinical practice. Methods. This observational study was conducted in patients with HER2-positive breast adenocarcinoma ≤1.5 cm who received trastuzumab-based adjuvant treatment in clinical practice. Clinical/histopathological data were retrieved from patients’ medical charts. Results. A total of 101 evaluable patients were enrolled (median age [range], 56.7 [49.0–64.8] years; ECOG 0, 98.0 %; ductal carcinoma, 88.1 %; lymph nodes N0, 79.2 %). Only five (5.0 %) patients received neoadjuvant treatment, while all patients underwent tumor surgery. Adjuvant trastuzumab was administered at a mean (±SD) dose of 5.9 ± 1.5 mg/kg/cycle, and mostly in a three-weekly schedule (89 [89.0 %] patients). The most frequent adjuvant therapy used with trastuzumab was chemotherapy (87 [86.1 %] patients), followed by radiotherapy (63 [62.4 %] patients) and hormone therapy (52 [51.5 %] patients). Chemotherapy regimens mainly included doxorubicin, cyclophosphamide and paclitaxel/docetaxel (n = 30), docetaxel and cyclophosphamide (n = 15), docetaxel and carboplatin (n = 13). Hormone therapy mainly included letrozole (n = 17) and tamoxifen (n = 17). Nine (8.9 %) patients reported trastuzumab-related adverse events; only one allergic reaction reached grade 3 toxicity. Conclusion. This study shows that trastuzumab-based adjuvant treatment of small HER2-positive breast cancer is mostly based on chemotherapy—mainly paclitaxel/docetaxel. Adjuvant administration of trastuzumab for small HER2-positive breast cancer seems to be similar to that used for larger tumors (AU)

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Ética de la equidad y justicia en el acceso al diagnóstico, tratamiento y rehabilitación de los pacientes con enfermedades raras / Ethics of equity and justice in access to diagnosis, treatment and rehabilitation of patients with rare diseases

Las enfermedades raras se definen por su reducida frecuencia en la población, lo que supone numerosas consecuencias adversas, tanto a nivel médico como social. Estas patologías, al ser poco conocidas, tienen un diagnóstico tardío y no cuentan con tratamientos específicos para muchas de ellas. Se caracterizan por ser enfermedades crónicas, degenerativas, invalidantes con calidad de vida disminuida, pérdida de autonomía, alto nivel de dolor y sufrimiento de la persona y su familia, y generalmente ponen en riesgo la vida. Aquellas que tienen un tratamiento específico son de tan alto costo que no pueden ser financiadas por el paciente sin el aporte estatal. Esta situación implica desde el punto de vista ético la necesidad de considerar el principio de Beneficencia y de Justicia Social en las decisiones que se adopten.

Rare diseases are defined by the reduced frequency in the population, leading to numerous adverse consequences, both at medical and social level. These pathologies, being little known, the diagnose is late or non-existent and there are no specific treatments for many of them. They are characterized by debilitating, degenerative, chronic diseases with decreased quality of life, loss of autonomy, high level of pain and suffering of the person and his family, and usually life threatening. Those with specific treatment are so costly that they can not be financed by the patient without the state contribution. This situation results from the ethical point of view the need to consider the principle of Beneficence and Social Justice in the decisions taken.

Adjuvant regimens with trastuzumab administered for small HER2-positive breast cancer in routine clinical practice.

PURPOSE: Trastuzumab has proven to improve the prognosis of HER2-positive breast cancer, but the information available about its administration for small tumors is still limited. Therefore, we assessed the use of adjuvant regimens with trastuzumab for the treatment of small HER2-positive breast cancer in routine clinical practice. METHODS: This observational study was conducted in patients with HER2-positive breast adenocarcinoma ≤1.5 cm who received trastuzumab-based adjuvant treatment in clinical practice. Clinical/histopathological data were retrieved from patients' medical charts. RESULTS: A total of 101 evaluable patients were enrolled (median age [range], 56.7 [49.0-64.8] years; ECOG 0, 98.0 %; ductal carcinoma, 88.1 %; lymph nodes N0, 79.2 %). Only five (5.0 %) patients received neoadjuvant treatment, while all patients underwent tumor surgery. Adjuvant trastuzumab was administered at a mean (±SD) dose of 5.9 ± 1.5 mg/kg/cycle, and mostly in a three-weekly schedule (89 [89.0 %] patients). The most frequent adjuvant therapy used with trastuzumab was chemotherapy (87 [86.1 %] patients), followed by radiotherapy (63 [62.4 %] patients) and hormone therapy (52 [51.5 %] patients). Chemotherapy regimens mainly included doxorubicin, cyclophosphamide and paclitaxel/docetaxel (n = 30), docetaxel and cyclophosphamide (n = 15), docetaxel and carboplatin (n = 13). Hormone therapy mainly included letrozole (n = 17) and tamoxifen (n = 17). Nine (8.9 %) patients reported trastuzumab-related adverse events; only one allergic reaction reached grade 3 toxicity. CONCLUSION: This study shows that trastuzumab-based adjuvant treatment of small HER2-positive breast cancer is mostly based on chemotherapy-mainly paclitaxel/docetaxel. Adjuvant administration of trastuzumab for small HER2-positive breast cancer seems to be similar to that used for larger tumors.

Phytoplankton production systems in a shellfish hatchery: variations of the bacterial load and diversity of vibrios.

AIMS: Outbreaks of disease caused by some Vibrio species represent the main production bottleneck in shellfish hatcheries. Although the phytoplankton used as food is one of the main sources of bacteria, studies of the associated bacterial populations, specifically vibrios, are scarce. The aim of the study was the microbiological monitoring of the microalgae as the first step in assessing the risk disease for bivalve cultures. METHODS AND RESULTS: Two phytoplankton production systems were sampled weekly throughout 1-year period in a bivalve hatchery. Quantitative analysis revealed high levels of marine heterotrophic bacteria in both systems throughout the study. Presumptive vibrios were detected occasionally and at low concentrations. In most of the cases, they belonged to the Splendidus and Harveyi clades. CONCLUSIONS: The early detection of vibrios in the microalgae may be the key for a successful bivalve culture. Their abundance and diversity were affected by factors related to the hatchery environment. SIGNIFICANCE AND IMPACT OF THE STUDY: This work represents the first long study where the presence of vibrios was evaluated rigorously in phytoplankton production systems and provides a suitable microbiological protocol to control and guarantee the quality of the algal cultures to avoid the risk of transferring potential pathogens to shellfish larvae and/or broodstock.

Effects of energy concentration of the diet on productive performance and egg quality of brown egg-laying hens differing in initial body weight.

The influence of AME(n) concentration of the diet on productive performance and egg quality traits was studied in Hy-Line brown egg-laying hens differing in initial BW from 24 to 59 wk of age. Eight treatments were arranged factorially with 4 diets varying in energy content (2,650, 2,750, 2,850, and 2,950 kcal of AME(n)/kg) and 2 initial BW of the hens (1,733 vs. 1,606 g). Each treatment was replicated 5 times (13 hens per replicate), and all diets had similar nutrient content per unit of energy. No interactions between energy content of the diet and initial BW of the hens were detected for any trait. An increase in energy concentration of the diet increased (linear, P < 0.05; quadratic P < 0.05) egg production, egg mass, energy efficiency (kcal of AME(n)/g of egg), and BW gain (P < 0.05) but decreased ADFI (linear, P < 0.001) and feed conversion ratio per kilogram of eggs (linear, P < 0.01; quadratic P < 0.01). An increase in energy content of the diet reduced Haugh units and the proportion of shell in the egg (P < 0.01). Feed intake (114.6 vs. 111.1 g/hen per day), AME(n) intake (321 vs. 311 kcal/hen per day), egg weight (64.2 vs. 63.0 g), and egg mass (58.5 vs. 57.0 g) were higher for the heavier than for the lighter hens (P < 0.01), but feed conversion ratio per kilogram of eggs and energy efficiency were not affected. Eggs from the heavier hens had a higher proportion of yolk and lower proportion of albumen (P < 0.01) and shell (P < 0.05) than eggs from the lighter hens. Consequently, the yolk-to-albumen ratio was higher (P < 0.001) for the heavier hens. It is concluded that brown egg-laying hens respond with increases in egg production and egg mass to increases in AME(n) concentration of the diet up to 2,850 kcal/kg. Heavy hens had higher feed intake and produced heavier eggs and more egg mass than light hens. However, feed and energy efficiency were better for the lighter hens.

Water quality assessment using satellite-derived chlorophyll-a within the European directives, in the southeastern Bay of Biscay.

The implementation of water quality European Directives requires an intensification of water quality monitoring, within the limits of the Exclusive Economic Zone. Remote sensing technologies can provide a valuable tool for frequent, synoptic, water-quality observations, over large areas. The aim of this study is to assess the ecological status of Basque coastal water bodies using satellite imagery from MODIS sensor, together with optical and chlorophyll-ain situ measurements. Thus, sea surface satellite-derived chl-a algorithms, the OC3 M, OC5 and a Local empirical algorithm, were compared against in situ measurements using satellite in situ match-ups, 90th Percentile (P90) monthly values for the 2005-2010 period. The OC5 algorithm corresponded most accurately with in situ measurements performed in the area, hence, it was selected. A P90 chlorophyll-a map was created with this algorithm to apply the classification scheme required by the directives. The classification of water bodies, based upon satellite-derived chlorophyll-a, could improve considerably the assessment of water quality.

Hepatitis C virus (HCV) treatment uptake and changes in the prevalence of HCV genotypes in HIV/HCV-coinfected patients.

The efficacy of current hepatitis C therapy in HIV/HCV-coinfected patients is largely dependent on HCV genotype. The annual prevalence of HCV genotypes/subtypes and their influence on HCV clearance with antiviral treatment were examined in a dynamic cohort of HIV/HCV-coinfected patients followed up in Madrid since 2000. Patients entered the cohort at first visit and left the cohort when HCV clearance was achieved with HCV therapy or when follow-up was interrupted for any reason, including death. A total of 672 HIV/HCV-coinfected patients constituted the cohort. The mean follow-up time was 5.5 years, corresponding to 4108 patient-years. Mean age at entry was 37 years, and 73% were men and 86% were intravenous drug users. Overall distribution of HCV genotypes was as follows: 57.1% HCV-1 (1a: 29.2%, 1b: 20.4%, unknown: 7.6%), 1.3% HCV-2, 25.4% HCV-3 and 15.9% HCV-4. A total of 274 (40.8%) patients were treated with peginterferon-ribavirin, of whom 116 (42.3%) achieved HCV clearance following 1-3 courses of therapy. The proportion of HCV-1/4 rose from 71.7% in 2000 to 76.8% in 2008, whereas the proportion of HCV-2/3 fell from 28.1% in 2000 to 23.2% in 2008. The yearly prevalence increased for HCV-1 (R(2) : 0.92, b: 0.59, P < 0.001) and HCV-4 (R(2) : 0.77, b: 0.33, P < 0.005) and conversely diminished for HCV-3 (R(2) : 0.94, b: -0.82, P < 0.001). In summary, the prevalence of HCV-1 and HCV-4 has increased over the last decade in HIV/HCV-coinfected patients, whereas conversely it has declined for HCV-3, in association with the wider use of HCV therapy (41%) in this population.

Cáncer de mama asociado a síndrome de Li-Fraumeni en dos hermanas / No disponible

Se presenta a dos hermanas diagnosticadas de un carcinoma de mama (CM), con el antecedente de que su madre fue diagnosticada de carcinoma de mama a los treinta y cuatro años y falleció cuatro años después. Consecuentemente, se hizo un estudio genético descartándose una mutación de los oncogenes BRCA1 y BRCA2. Sin embargo, sí se evidenció una alteración a nivel del gen supresor p53, característico del síndrome de Li-Fraumeni (SLF). El SLF es una rara enfermedad autosómica dominante que afecta fundamentalmente a pacientes jóvenes y que consiste en una predisposición a desarrollar una amplia variedad de tumores, entre ellos el CM(AU)

We present two sisters who were diagnosed as having breast cancer; being their mother diagnosed as having breast cancer when she was thirty-four years old, and having died four years later. Hence, we decided to make a genetic testing, which was negative in BRCA1 and BRCA2 mutation. However, a mutation in p53 tumor suppressor gene was detected in the genetic study, which is characteristic of Li-Fraumeni syndrome (LFS). LFS is a rare autosomal dominant hereditary disorder that frequently appears in young patients. Patients with LFS are at risk for a wide range of malignancies, being breast cancer particularly frequent(AU)

La muerte cerebral y su significado / Brain death and its meaning

The diagnosis of brain death is considered in Occidental World as a new way of being dead. Nevertheless, in our country, this concept has not been completely accepted by the general population neither by health workers. In our experience, a significant percentage of the professionals working in pediatric services believe that a child in brain death is not dead. Considering this situation it seems very important that pediatric services should receive special training about the meaning of this condition. Those professionals that do not accept brain death, as the death of the individual should be allowed to stay away from any decision concerning that child. The Chilean Legislation is reviewed and an ethical analysis is also done.

El diagnóstico de muerte cerebral es considerado en el Mundo Occidental como una nueva forma de estar muerto. Este concepto, en nuestro medio no está completamente incorporado tanto en la población general como en el equipo de salud. En nuestra experiencia un porcentaje significativo de profesionales de servicios pediátricos consideran que un niño en muerte cerebral, no ha fallecido. Considerando esta situación se estima que debería hacerse una capacitación en los servicios sobre esta condición y permitir que aquellos profesionales que no acepten la muerte cerebral como equivalente a la muerte del individuo puedan no verse involucrados en las decisiones que se adopten con estos niños. Se revisa la Legislación Chilena y se hace un análisis ético de la muerte cerebral.

Subacute cerebellar degeneration as paraneoplastic syndrome: initial symptom of breast cancer with HER2 overexpression.

We report the case of a patient with subacute cerebellar degeneration presenting as paraneoplastic syndrome, preceding the final diagnosis of breast cancer. The tumor had high HER2 overexpression, so a weekly regimen of paclitaxel/trastuzumab was started after surgery of the primary breast tumor. Negativity of specific antineuronal antibodies and clinical stabilization of the patient was achieved after 12 cycles of treatment. The interest of this case is the unusual presentation and the targeted therapeutic approach that has been used.

Overview of the pharmacogenetics of HIV therapy.

The administration of standard doses of most antiretroviral drugs results in significant variations in plasma drug concentrations among different individuals, influencing antiviral activity as well as incidence of drug-related toxicities. The reasons for this large inter-individual variability in drug levels are multifactorial, and involve differences in metabolism related to gender, concomitant medications, drug compliance, underlying diseases and genetic factors. Pharmacogenetics is the discipline that analyses the genetic basis for the inter-individual variation in the body disposition of drugs. One of its main goals is to give grounds to individualized treatment. The majority of pharmacogenetic traits so far have involved drug metabolism. This is the case for the inherited variation in the pharmacokinetics and pharmacodynamics of drugs such as hydralazine or isoniazid, which is due to polymorphisms in the N-acetyltransferase-2 (NAT2) gene, which allows splitting the population into three categories: slow, intermediate, and fast metabolizers. Pharmacogenetic studies conducted so far with antiretroviral drugs have focussed on metabolizer enzymes at the liver and on transporter proteins on cell membranes. Herein, we review the most relevant metabolizer enzymes and protein transporters, along with the genetic polymorphisms, which seem to influence the pharmacokinetics of antiretroviral drugs, ultimately determining its efficacy and toxicity.

Eclampsia: su responsabilidad en el incremento de episodios perinatales adversos / Eclampsia: its role in the increase of adverse perinatal events

Objetivo: En todos los países del mundo la hipertensión asociada al embarazo figura dentro de las tres primeras causas de muerte materna. El objetivo fue cuantificar el riesgo perinatal que representa la eclampsia en nuestro hospital, comparado con pacientes hipertensas que no desarrollaron eclampsia y pacientes sanas. Pacientes y métodos: El diseño fue retrospectivo, de corte transversal, analizando la totalidad los partos asistidos en el Instituto de Maternidad Nuestra Señora de las Mercedes de San Miguel de Tucumán entre el 1 de enero y el 31 de diciembre de 1998. Se asistieron 13.646 nacimientos , 28 pacientes sufrieron eclampsia (0,2%) y 915 (6,7%) algún estado hipertensivo del embarazo (EHE), con 5.954 pacientes sanas que no presentaron ninguna otra patología asociada al embarazo. Resultados: Las pacientes que sufrieron eclampsia presentaron significativamente menor peso al nacer, edad gestacional al parto y score de Apgar al minuto 5. Hay un incremento significativo del riesgo de cesárea, depresión al nacer BPN y MBPN en las pacientes que cursaron estados hipertensivos del embarazo frente a controles. Con un significativo incremento adicional del riesgo si desarrolló eclampsia. La aparición de eclampsia incrementa el riesgo de mortalidad fetal tardía 3,3 veces sobre las hipertensas, pero casi 20 veces sobre la población sana control. La mortalidad perinatal I casi 5 veces sobre la de las pacientes hipertensas y 18 veces más que la población sana control. Discusión: En esta serie podemos cuantificar el dramático incremento de la morbimortalidad que presentan la madre y su hijo, cuando aparece esta temida y en muchos casos prevenible complicación de los estados hipertensivos del embarazo (AU)

Pesquisa etiológica en espasmos masivos / Etiologic research in massive spasms

Con el objeto de identificar un factor etiológico se aplicó un protocolo de estudio sistemático en 16 lactantes que presentaban espasmos masivos. En dos pacientes hubo antecedentes familiares relevantes, en tanto que cinco presentaron afecciones perinatales o postnatales graves. Diez niños presentaron retardo psicomotor y ocho otras crisis previo al inicio de EM. El examen físico reveló microcefalia, dismorfias, manchas hipopigmentadas de la piel, síndrome piramidal. Las técnicas de neuro-imagen demostraron hallazgos positivos en 9 casos, atrofia en 7, porencefalia en 3, calcificaciones en uno y agenesia del cuerpo calloso en uno. El laboratorio permitió el diagnóstico de dos casos con enfermedades metabólicas: hiperlactatemia y enfermedad de orina olor a jarabe de arce. Dos pacientes se catalogaron como criptogenéticos y 14 como sintomáticos. Entre los últimos en doce casos se identificó razonablemente una etiología. Este estudio enfatiza el valor de la búsqueda etiológica en EM, puesto que aporta el tratamiento específico y/o consejo genético en algunos pacientes

Tratamiento de espasmos masivos con ACTH sintético / Treatment of massive spasms with synthetic ACTH

Diez lactantes portadores de espasmos masivos (EM) e hispsarritmia recibieron un esquema de tratamiento con ACTH sintético 0,05 mg*kg*dosis 3 veces por semana por 2 semanas. En seis casos se obtuvo remisión completa de las crisis y cambios dramáticos en el electroencefalograma, en tres casos hubo una respuesta parcial. En cinco casos la respuesta completa ocurrió durante la primera semana de tratamiento. Se observó una relación significativa entre precocidad del tratamiento y respuesta favorable (Fisher p < 0,02). Este esquema de tratamiento no produjo efectos laterales severos en paciente alguno. Durante el seguimiento (X: 6,2 meses) se observó recaída en un caso de respuesta completa, en tanto que cinco pacientes mantienen su respuesta inicial con un desarrollo normal o levemente retardado. Los cinco pacientes restantes presentan un retardo severo y crisis de difícil tratamiento. Futuros estudios debieran abordar la eficacia de otros esquemas de tratamiento, balanceando éxito y efectos laterales

Efectos de la terapia con fenobarbital en pacientes pediátricos con diferente estado nutricional / Phenobarbital therapy effects on pediatric patients with different nutritional status

El objetivo del presente trabajo fue estudiar si los efectos adversos del fenobarbital en relación a metabolismo fosfocálcico y hepatotoxicidad se acentúan cuando se agrega al cuadro clínico un déficit nutricional. También se determinó la fracción de droga libre del fármaco y su relación con los niveles de albúmina sérica. Se encontró un número importante de niños con estado nutricional normal que presentaba hipoalbuminemia (24,1%), hipofosfatemia (20,7%) y actividad aumentada de las fosfatasas alcalinas (44,8%) y de la transaminasa glutámico oxaloacética (32,1%). Al comparar este grupo con el de los pacientes con déficit nutricional avanzado, se encontró diferencia significativa sólo en relación a fósforo (p<0,025), encontrando un 46,2% con hipofosfatemia y un 42,8% con hipoalbuminemia. Ambos estados nutricionales no mostraron cambios significativos en la fracción de droga libre, no constituyéndose así en otro factor de riesgo