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

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Bidirectional light-induced conductance switching in molecular wires containing a dimethyldihydropyrene unit.

Photochromic coordination polymers, based on zinc(ii) bis-terpyridine-appended dimethyldihydropyrene building blocks, have been synthesized following stepwise synthesis on a surface yielding photo-switchable molecular junctions. Under irradiation, reversible structural changes occur by the isomerization of the photosensitive units, thus inducing conductance switching of the molecular junctions with a good reproducibility.

Electrochemical control of the switching process of photochromic dimethyldihydropyrene derivatives.

The electrochemical control of the isomerization process of a photo-switchable dimethyldihydropyrene (DHP) derivative has been investigated. Spectro-electrochemical experiments clearly evidence that the substitution of the DHP core by electron-withdrawing entities can be used to control the opening/closing process.

Self-assembled dimethyldihydropyrene-pyridyl substituted ligands with zinc(ii) meso-tetraphenylporphyrin via axial coordination.

A series of dimethyldihydropyrene (DHP)-pyridyl photochromic derivatives has been synthesized and its photochemical behaviour characterized by spectroscopic and electrochemical methods. The corresponding noncovalently-linked electron donor-acceptor complexes have been isolated. They combine the DHP-pyridyl ligand as a donor and the zinc(ii) tetraphenylporphyrin as acceptor. Such association allowed to explore the efficiency of dative bonds to monitor the interactions between the two units.

Heart Rate Variability: a Follow-up in Elite Soccer Players Throughout the Season.

Heart rate variability (HRV) can provide useful information on physiological adaptations to training, but its role is unknown in professional soccer. The aim of this study was to determine an HRV profile in professional soccer over a season. A total of 504 records were made of the heart beat signal throughout a season from 22 professional soccer players. HRV was recorded in a sitting position, early morning and fasting for a period of 10 min. Standard deviation 1 and 2 (SD1, SD2), standard deviation of normal to normal R-R intervals (SDNN), Root Mean Square of the Successive Differences (rMSSD), percentage of RR intervals > 50 ms (pNN50), Sample Entropy (SampEn), Stress Score (SS) and sympathetic/parasympathetic ratio (S/PS ratio) were calculated. SDNN, rMSSD, pNN50, SD1 and SD2 showed an identical behaviour throughout the season, with lower values in the pre-season and the end of the season. SS and S/PS ratio indicated a sympathetic stress alert in the same periods. A weekly recording of the HRV over a 10 min period that includes a Poincaré plot with SS and S/PS ratio and at least one variable of the time domain is a useful tool for the follow-up of the individual assimilation of weekly workloads, including the game.

Effects of eccentric overload bout on change of direction and performance in soccer players.

The aims of this study were to analyse the effects of eccentric overload training (EOT) on kinetic parameters during change of direction (COD) and performance related to sprinting and jumping abilities. 20 male soccer players performed 2 different protocols: 1) 5-min cycling warm-up and 2) 5-min cycling warm-up+YoYo half-squat exercise. The outcome measured included vertical ground reaction force (vGRF) and propulsive force (PvGRF), time to vGRF (T_vGRF) and propulsive force (T_PvGRF), contact time (CT), eccentric (ECC_IMP), concentric (CONC_IMP) and total (TOT_IMP) impulses and moments (Mx, My and Mz) during 2 COD tasks. Additionally, subjects performed a counter-movement jump (CMJ) and 20 m sprint tests. Results showed a substantial better improvement (likely to almost certainly) in vGRF (ES: 0.84), vAGRF (ES: 0.72), CT (ES: 0.48), My (ES: 0.35), Mz (ES: 0.44) and ECC_IMP (ES: 0.45) during crossover cutting maneuver, whereas during side-step cutting maneuver Time_ECC (ES: 0.68), CT (ES: 0.64), vGRF (ES: 0.48) and My (ES: 0.47) were substantially enhanced (likely). Furthermore, substantial better performance was found in CMJ (ES: 0.47; very likely) and 20 m (ES: 0.20; possibly). In conclusion, EOT produced a better muscle activation during 2 different COD tasks and greater sprinting and jumping performance.

Generation and molecular characterization of a monoclonal antibody reactive with conserved epitope in sphingomyelinases D from Loxosceles spider venoms.

We report the production of a neutralizing monoclonal antibody able to recognize the venoms of three major medically important species of Loxosceles spiders in Brazil. The mAb was produced by immunization of mice with a toxic recombinant L. intermedia sphingomyelinase D {SMases D isoform (rLiD1)} [1] and screened by enzyme-linked immunosorbent assay (ELISA) using L. intermedia, L. laeta and L. gaucho venoms as antigens. One clone (LiD1mAb16) out of seventeen anti-rLiD1 hybridomas was cross-reactive with the three whole Loxosceles venoms. 2D Western blot analysis indicated that LiD1mAb16 was capable of interacting with 34 proteins of 29-36kDa in L. intermedia, 33 in L. gaucho and 27 in L. laeta venoms. The results of immunoassays with cellulose-bound peptides revealed that the LiD1mAb16 recognizes a highly conserved linear epitope localized in the catalytic region of SMases D toxins. The selected mAb displayed in vivo protective activity in rabbits after challenge with rLiD1. These results show the potential usefulness of monoclonal antibodies for future therapeutic approaches and also opens up the perspective of utilization of these antibodies for immunodiagnostic assays in loxoscelism.

Cerebrospinal Aß11-x and 17-x levels as indicators of mild cognitive impairment and patients' stratification in Alzheimer's disease.

In the present work, the concentrations of Aß11-x and Aß17-x peptides (x=40 or 42), which result from the combined cleavages of ß-amyloid precursor protein (AßPP) by ß'/α or α/γ-secretases, respectively, were assessed in cerebrospinal fluid (CSF) samples from patients with Alzheimer's disease (AD) or mild cognitive impairment (MCI). Specific multiplexed assays were set up using new anti-40 and anti-42 monoclonal antibodies (mAbs) for the capture of these N-truncated Aß peptides and anti-11 or anti-17 mAbs for their detection. The specificity, sensitivity and reproducibility of such assays were assessed using synthetic peptides and human cell models. Aß11-x and Aß17-x were then measured in CSF samples from patients with AD (n=23), MCI (n=23) and controls with normal cognition (n=21). Aß11-x levels were significantly lower in patients with MCI than in controls. Compared with the combined quantification of Aß1-42, total Tau (T-Tau) and phosphorylated Tau (P-Tau; AlzBio3, Innogenetics), the association of Aß11-40, Aß17-40 and T-Tau improved the discrimination between MCI and controls. Furthermore, when patients with MCI were classified into two subgroups (MCI ≤1.5 or ≥2 based on their CDR-SB (Cognitive Dementia Rating-Sum of Boxes) score), the CSF Aß17-40/Aß11-40 ratio was significantly higher in patients with CDR-SB ≤1.5 than in controls, whereas neither Aß1-42, T-Tau nor P-Tau allowed the detection of this subpopulation. These results need to be confirmed in a larger clinical prospective cohort.

Revisión sobre la lesión de la musculatura isquiotibial en el deporte: factores de riesgo y estrategias para su prevención / Review on the hamstring muscle injury in sport: risk factors and prevention strategies

La lesión aguda de la musculatura isquiotibial es una de las más frecuentes en el ámbito deportivo, presentando una alta incidencia e, incluso, una elevada tasa de recurrencia. Ambos fenómenos se han relacionado a menudo con la ineficacia de las estrategias utilizadas para prevenir la aparición de esta lesión, ya que éstas no tienen en consideración, en muchas de las ocasiones, el carácter multifacético de la lesión. Además, la evidencia científica sobre los factores de riesgo asociados a la lesión isquiotibial es limitada aún, lo que dificulta el desarrollo de estrategias de prevención apropiadas. En base a lo expuesto, los objetivos de esta revisión son: analizar los factores de riesgo asociados a esta lesión y, de acuerdo a estos, describir las estrategias utilizadas para prevenir dichas lesiones(AU)

Acute hamstrings injury is one of the most common in sport, presenting a high incidence and even a high recurrence rate. Both are often associated with the ineffectiveness of the strategies used to prevent the occurrence of this injury, because they do not take into cosideration, in many instances, the multifaceted nature of the injury. In addition, scientific evidence about the risk factors associated with hamstring injury is still low, limiting the development of appropriate prevention strategies. Based on the above, the aims of this review are: analyze the risk factors associated with this injury and, according to them, describe the strategies used to prevent injuries(AU)

[Nutritional support and risk factors of appearance of enterocutaneous fistulas]. / Soporte nutricional y factores de riesgo de aparición de fístulas enterocutáneas.

INTRODUCTION: Among the different factors described, nutritional support has been associated to prevention and management of enterocutaneous fistulae (ECF). OBJECTIVES: To assess the influence that the parameters related to nutritional, clinical status, and surgical variables have on the occurrence of ECF. METHODS: An observational case/control retrospective study was performed on patients admitted to the General and Digestive Surgery Department. The parameters analyzed were: diagnosis, body mass index (BMI), pathologic personal history, number of surgical interventions (SI) and complications (previous infection, bleeding, and ischemia). In patients with SI, we analyzed: number and type of SI, time until onset of nutritional support, and type of nutritional support. We performed a multiple logistic uni- and multivariate regression analysis by using the SPSSv.19.0 software. RESULTS: The primary diagnoses related to the occurrence of ECF were pancreatic pathology (OR = 5.346) and inflammatory bowel disease (IBD) (OR = 9.329). The surgical variables associated to higher prevalence of ECF emergency SI (OR = 5.79) and multiple SI (OR = 4.52). Regarding the nutritional variables, the late onset of nutrition (more than three days after SI) was associated to the occurrence of ECF (OR = 3.82). CONCLUSIONS: In surgical patients, early nutritional support , independently of the route of administration, decreases the occurrence of fistulae. Pancreatic pathology, IBD, emergency SI, and multiple SI were associated to higher prevalence of ECF. The variable hyponutrition appears as a risk factor that should be confirmed in further studies.

Soporte nutricional y factores de riesgo de aparición de fístulas enterocutáneas / Nutritional support and risk factors of appearance of enterocutaneous fistulas

Introducción: Entre los diferentes factores descritos, el soporte nutricional se ha asociado a la prevención y el tratamiento de las fístulas enterocutáneas (FEC). Objetivos: Evaluar la influencia que los parámetros relacionados con variables nutricionales, estado clínico y quirúrgicas tienen sobre la aparición de FEC. Métodos: Se realizó un estudio retrospectivo observacional de casos/controles en pacientes ingresados en Cirugía General y Digestiva. Se analizaron: diagnóstico, índice de masa corporal (IMC), antecedentes patológicos, número de intervenciones quirúrgicas (IQ) y complicaciones (infección previa, sangrado e isquemia). En los pacientes con IQ se analizaron: número y tipo de IQ, tiempo hasta el inicio del soporte nutricional y tipo de soporte nutricional. El análisis estadístico uni/multivariante de regresión logística múltiple se realizó mediante el software SPSSv.19.0. Resultados: Los diagnósticos primarios que se relacionaron con la aparición de FEC fueron la patología pancreática (OR = 5,346) y la enfermedad inflamatoria intestinal (EII) (OR = 9,329). Las variables quirúrgicas que se asociaron con mayor prevalencia de FEC fueron IQ de urgencia (OR = 5,79) e IQ múltiples (OR = 4,52). En cuanto a las variables nutricionales, el inicio tardío de la nutrición (más de tres días después de IQ) se relacionó con la aparición de FEC (OR = 3,82). Conclusiones: En los pacientes quirúrgicos, el soporte nutricional precoz, independientemente de la vía de administración, disminuye la aparición de fístulas. La patología pancreática, la EII, las IQ urgentes y las IQ múltiples se asociaron con mayor prevalencia de FEC. La variable desnutrición se apunta como un factor de riesgo que debería corroborarse en estudios posteriores (AU)

Introduction: Among the different factors described, nutritional support has been associated to prevention and management of enterocutaneous fistulae (ECF). Objectives: To assess the influence that the parameters related to nutritional, clinical status, and surgical variables have on the occurrence of ECF. Methods: An observational case/control retrospective study was performed on patients admitted to the General and Digestive Surgery Department. The parameters analyzed were: diagnosis, body mass index (BMI), pathologic personal history, number of surgical interventions (SI) and complications (previous infection, bleeding, and ischemia). In patients with SI, we analyzed: number and type of SI, time until onset of nutritional support, and type of nutritional support. We performed a multiplelogistic uni- and multivariate regression analysis by using the SPSSv.19.0 software. Results: The primary diagnoses related to the occurrence of ECF were pancreatic pathology (OR = 5.346) and inflammatory bowel disease (IBD) (OR = 9.329). The surgical variables associated to higher prevalence of ECF emergency SI (OR = 5.79) and multiple SI (OR = 4.52). Regarding the nutritional variables, the late onset of nutrition (more than three days after SI) was associated to the occurrence of ECF (OR = 3.82). Conclusions: In surgical patients, early nutritional support , independently of the route of administration, decreases the occurrence of fistulae. Pancreatic pathology, IBD, emergency SI, and multiple SI were associated to higher prevalence of ECF. The variable hyponutrition appears as a risk factor that should be confirmed in further studies (AU)

Adjuvant hormonal therapy in perimenopausal patients.

This section considers the treatment options for perimenopausal women with breast cancer. The perimenopause period begins in the so-called stage 2 of menopausal transition (early menopausal transition, where the length of the cycles changes by 7 days or more) and ends after 12 months of amenorrhea. It is characterized by an early increase in follicle-stimulating hormone and is associated with the presence of anovulatory cycles, irregular periods, and loss of menstrual cycles. The recommended treatment is tamoxifen (TAM) with or without ovarian ablation for 2 or 3 years followed by a re-evaluation. TAM should be maintained if the patient is premenopausal and aromatase inhibitors (AI) are recommended once the menopausal status is confirmed. Ovarian suppression is an acceptable adjuvant therapy in those patients with hormone-sensitive tumors. AI should only be used in postmenopausal women or in combination with chemical castration in premenopausal women. This supplement paper includes the key points of roundtable presentations and discussions of hormonal therapy in breast cancer.

[Standard parenteral nutrition preparations and caloric adjustment]. / Preparados estándar de nutrición parenteral y ajuste calórico.

INTRODUCTION: In parenteral nutrition it is necessary to adjust the intake to the estimated caloric requirements. These needs may be achieved by the use of bi- or tricameral nutrition (EPN), although they present some rigidity regarding their composition. OBJECTIVE: To assess the adequacy of caloric intake using EPN, to determine the factors conditioning it and the associated complications. METHODS: Cohort, prospective, and observational study for 9 months in surgical patients. The calculated needs were compared with actual intake. The factors conditioning the excess and deficit (weight, age, stress factor, height, glycemia, and triglyceridemia) were studied by means of a multivariant method. The metabolic complications associated to the excess or deficit (hyperglycemias, hypertriglyceridemias) were studied by using the Student's t test. The theoretical calculations with the Harris-Benedict and the Mifflin equations were compared by lineal correlation regression. RESULTS: 94 patients were studied. In 87% of them, the caloric intake was within the +/- 15% range of the theoretical mean. Thirty patients had caloric excess, whereas 61 had deficit. Patients with high weight (> 68 kg), stress factor > 1.2, and hypertriglyceridemias (> 3 mmol/L) had higher risk for caloric deficit. Twenty two point eight percent had hyperglycemias that were correlated with caloric excess. Nineteen point eight percent had hypertriglyceridemias associated to caloric deficit. When comparing both formulas, the values correlated well except for those patients with low weight and advanced age. DISCUSSION: Although EPN fits the caloric requirements in most of the patients, in those with high weight, hypercatabolism, and hypertriglyceridemia there is a risk for caloric deficit.

Preparados estándar de nutrición parenteral y ajuste calórico / Standard parenteral nutrition preparations and caloric adjustment

Introducción: En nutrición parenteral es necesario adecuar el aporte a los requisitos calóricos estimados. Estas necesidades se podrían cubrir mediante preparados bi/tricamerales (NPE) aunque presenten rigidez en su composición. Objetivo: Evaluar la adecuación del aporte calórico al utilizar NPE, determinar los factores que la condicionan y las complicaciones asociadas. Métodos: Estudio de cohortes, observacional y prospectivo durante nueve meses en pacientes quirúrgicos. Se compararon las necesidades calculadas con el aporte real. Se estudiaron que factores condicionaban el exceso y el déficit (peso, edad, factor de estrés, altura, glucemia y trigliceridemia) mediante un modelo multivariante. Se estudiaron las complicaciones metabólicas (hiperglucemias, hipertrigliceridemias) asociadas al exceso o al déficit mediante la t de Student. Se compararon los cálculos teóricos de la ecuación de Harris-Benedict y de Mifflin mediante una regresión lineal-correlación. Resultados: Se estudiaron 94 pacientes. En el 87% el aporte calórico estaba dentro del rango ± 15% de la media teórica. 30 pacientes estuvieron en exceso calórico y 61 en déficit. Los pacientes de peso elevado (> 68 kg), factor de estrés superior a 1,2 e hipertrigliceridemias (> 3 mmol/L) tenían mayor riesgo de déficit calórico. El 22,8% presentaron hiperglucemias que se relacionaron con exceso calórico. El 19,8% presentaron hipertrigliceridemias que se asociaron con déficit calórico. En la comparación de las dos fórmulas los valores se correlacionaban excepto en pacientes con bajo peso y edad avanzada. Discusión: Aunque la NPE se adecua a los requisitos calóricos de la mayoría de los pacientes, en pacientes con elevado peso, hipercatabolismo e hipertrigliceridemia existe un riesgo de déficit (AU)

Introduction: In parenteral nutrition it is necessary to adjust the intake to the estimated caloric requirements. These needs may be achieved by the use of bi- or tricameral nutrition (EPN), although they present some rigidity regarding their composition. Objective: To assess the adequacy of caloric intake using EPN, to determine the factors conditioning it and the associated complications. Methods: Cohort, prospective, and observational study for 9 months in surgical patients. The calculated needs were compared with actual intake. The factors conditioning the excess and deficit (weight, age, stress factor, height, glycemia, and triglyceridemia) were studied by means of a multivariant method. The metabolic complications associated to the excess or deficit (hyperglycemias, hypertriglyceridemias) were studied by using the Student's t test. The theoretical calculations with the Harris-Benedict and the Mifflin equations were compared by lineal correlation regression. Results: 94 patients were studied. In 87% of them, the caloric intake was within the ± 15% range of the theoretical mean. Thirty patients had caloric excess, whereas 61 had deficit. Patients with high weight (> 68 kg), stress factor > 1.2, and hypertriglyceridemias (> 3 mmol/L) had higher risk for caloric deficit. Twenty two point eight percent had hyperglycemias that were correlated with caloric excess. Nineteen point eight percent had hypertriglyceridemias associated to caloric deficit. When comparing both formulas, the values correlated well except for those patients with low weight and advanced age. Discussion: Although EPN fits the caloric requirements in most of the patients, in those with high weight, hypercatabolism, and hypertriglyceridemia there is a risk for caloric deficit (AU)

Endocrine therapy of metastatic breast cancer

Breast cancer growth and dissemination is regulated by estrogen and different growth factor receptor signalling pathways. The increasing knowledge of the biology of breast cancer regarding the interaction of these signalling pathways provides a tool to understand endocrine therapies response and resistance mechanisms. In patients with slowly progressive disease, no visceral involvement, and minimal symptoms, endocrine therapy could be the strategy of choice, even if the tumor has low estrogen receptor expression. Ovarian suppression and tamoxifen are recommended for premenopausal patients whether aromatase inhibitors are the option for postmenopausal ones. Chemotherapy still remains as the right alternative for hormone unresponsive or resistant patients. This is a review focused on the different strategies and combinations of endocrine therapies for metastatic breast cancer patients considering the potential strategies clinically tested to overcome resistance and the different treatments of choice available for each scenario of disseminated disease (AU)

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Brain metastasis and carcinomatous meningitis from vulvar squamous cell carcinoma: case report.

BACKGROUND: Brain metastasis and carcinomatous meningitis from gynecological tumors are an uncommon event, usually related to choriocarcinoma, ovarian and cervical cancer. CASE: A 74-year-old woman was diagnosed with locally advanced vulvar squamous carcinoma. Initial therapy consisted of multiagent chemotherapy and vulvar, pelvis and groin irradiation. The patient subsequently developed widely spread metastatic disease including brain and meningeal metastases. CONCLUSION: The rising incidence of central nervous system metastasis in the last two decades is probably associated with treatment-related improvement in life expectancy. To our knowledge, this is the first case reported of brain metastases and meningeal carcinomatosis associated with vulvar squamous cell carcinoma.

Focalidad neurológica en el paciente anciano / Neurological focality in elderly patient

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