Review of concepts in therapeutic decision-making in HER2-negative luminal metastatic breast cancer.

PURPOSE: Hormone receptor (HR)-positive, Human epidermal growth factor receptor 2 (HER2)-negative metastatic breast cancer (MBC) requires a therapeutic approach that takes into account multiple factors, with treatment being based on anti-estrogen hormone therapy (HT). As consensus documents are valuable tools that assist in the decision-making process for establishing clinical strategies and optimize the delivery of health services, this consensus document has been created with the aim of developing recommendations on cretiera for hormone sensitivity and resistance in HER2-negative luminal MBC and facilitating clinical decision-making. METHODS: This consensus document was generated using a modification of the RAND/UCLA methodology, which included the definition of the project and identification of issues of interest, a non-exhaustive systematic review of the literature, an analysis and synthesis of the scientific evidence, preparation of recommendations, and external evaluation with a panel of 64 medical oncologists specializing in breast cancer. RESULTS: A Spanish panel of experts reached consensus on 32 of the 32 recommendations/conclusions presented in the first round and were accepted with an approval rate of 100% about definition of metastatic disease not susceptible to local curative treatment, definition of hormone sensitivity and hormone resistance in metastatic luminal disease and therapeutic decision-making. CONCLUSION: We have developed a consensus document with recommendations on the treatment of patients with HER2-negative luminal MBC that will help to improve therapeutic benefits.

[Mental development trajectories of a group of preterm babies from 1 to 30 months of age]. / Trayectorias de desarrollo mental de un grupo de bebes prematuros de 1 a 30 meses.

INTRODUCTION: This research falls within the category of longitudinal studies assessing the evolution of prematurely born infants with the use of standardized tests. AIMS: To analyze the trajectory of the mental development of a group of premature infants and to identify if gestational age is a significant predictor of their evolution. SUBJECTS AND METHODS: 359 prematurely born infants were assessed at three stages of their development (between 1-9 months, 10-18 months and 19-30 months of age), using the Bayley Scales of Infant DEVELOPMENT. To analyze the trajectory of the sample mental development, a linear mixed model procedure was applied. RESULTS: The trajectories of the mental development of these children conform to a model of the quadratic development curve. The results show that gestational age is a significant predictor of the initial score that explains 34% of the total interindividual variability. CONCLUSIONS: Children with lowest initial scores are those who most increase them with age, an important fact for the prediction of premature newborns future development. This fact should be taken into account regarding negative prognoses in the first year of life.

TITLE: Trayectorias de desarrollo mental de un grupo de bebes prematuros de 1 a 30 meses.Introduccion. Esta investigacion se inscribe en los estudios de corte longitudinal para evaluar la evolucion de los recien nacidos prematuros con el uso de pruebas estandarizadas. Objetivos. Analizar la trayectoria del desarrollo mental de un grupo de recien nacidos prematuros e identificar si la edad gestacional es un predictor significativo de su evolucion. Sujetos y metodos. Se evaluo a 359 recien nacidos prematuros en tres momentos de su desarrollo (entre 1 y 9 meses, entre 10 y 18 meses, y entre 19 y 30 meses de edad), utilizando las escalas Bayley de desarrollo infantil. Para analizar la trayectoria del desarrollo mental de la muestra se aplico el procedimiento de modelos lineales mixtos. Resultados. Las trayectorias del desarrollo mental de estos niños se ajustan a un modelo de la curva de desarrollo cuadratica. Los resultados muestran que la edad gestacional es un predictor significativo de la puntuacion inicial que explica el 34% del total de la variabilidad interindividual. Conclusiones. Los niños con puntuaciones iniciales mas bajas son los que mas incrementan sus puntuaciones con la edad, un dato importante de cara a la prediccion del futuro desarrollo de los prematuros y que previene sobre la realizacion de pronosticos negativos en el primer año de vida.

Preclinical and clinical development of palbociclib and future perspectives

Cyclin-dependent kinases (CDKs) play a key role in cell cycle regulation, which makes them a clear therapeutic target to interfere with cell division and proliferation in cancer patients. Palbociclib, a specific inhibitor of CDK4/6 with outstanding clinical efficacy data and limited toxicity, has been recently approved for the treatment of hormone receptor (HR)-positive human epidermal growth factor receptor 2 (HER2)-negative locally advanced or metastatic breast cancer, either in combination with an aromatase inhibitor or in combination with fulvestrant in women who have received prior endocrine therapy. This review describes the mechanism of action, preclinical experiences and clinical data of palbociclib, with a special focus on integrating this data with the positioning of palbociclib in the current clinical guidelines for advanced HR-positive/HER2-negative breast cancer. Aspects of the ongoing major studies are also presented, as well as future prospects in the development of palbociclib

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Preclinical and clinical development of palbociclib and future perspectives.

Cyclin-dependent kinases (CDKs) play a key role in cell cycle regulation, which makes them a clear therapeutic target to interfere with cell division and proliferation in cancer patients. Palbociclib, a specific inhibitor of CDK4/6 with outstanding clinical efficacy data and limited toxicity, has been recently approved for the treatment of hormone receptor (HR)-positive human epidermal growth factor receptor 2 (HER2)-negative locally advanced or metastatic breast cancer, either in combination with an aromatase inhibitor or in combination with fulvestrant in women who have received prior endocrine therapy. This review describes the mechanism of action, preclinical experiences and clinical data of palbociclib, with a special focus on integrating this data with the positioning of palbociclib in the current clinical guidelines for advanced HR-positive/HER2-negative breast cancer. Aspects of the ongoing major studies are also presented, as well as future prospects in the development of palbociclib.

New clinical trials regulation in Spain: analysis of royal decree 1090/2015

The coming into force of Directive 2001/20/EC represented a step forward in harmonising clinical trial regulation in European countries, guaranteeing a uniform protection of subjects participating in clinical research across Europe. However, it led to a disproportionate increase in the bureaucratization, and thus, it became evident that procedures needed to be simplified without detriment to patient’s safety. Thus, Regulation 536/2014, that repealed Directive 2001/20/EC, with the aim of decreasing the growing bureaucratization and stimulating clinical research in Europe, established simplified procedures, such as regulating a common procedure for authorising trials in Europe, the institution of strict assessment timelines, or the definition of new concepts, such as «low-intervention clinical trial». The legal form of a Regulation allowed the norm to be directly applied to Member States without the need for transposition. By means of the new Royal Decree, the national legislation is adapted to make the application of the regulation feasible and it allows the development of the aspects that the Regulation leaves to national legislation. Both documents seek to stimulate clinical research with medicinal products to foster knowledge, facilitate transparency, and reinforce subjects’ safety. This will surely be the case, but with this revision, we will look at the novelties and key aspects that are most relevant to investigators and we will analyse the consequences for all parties involved in clinical research (AU)

No disponible

New clinical trials regulation in Spain: analysis of royal decree 1090/2015.

The coming into force of Directive 2001/20/EC represented a step forward in harmonising clinical trial regulation in European countries, guaranteeing a uniform protection of subjects participating in clinical research across Europe. However, it led to a disproportionate increase in the bureaucratization, and thus, it became evident that procedures needed to be simplified without detriment to patient's safety. Thus, Regulation 536/2014, that repealed Directive 2001/20/EC, with the aim of decreasing the growing bureaucratization and stimulating clinical research in Europe, established simplified procedures, such as regulating a common procedure for authorising trials in Europe, the institution of strict assessment timelines, or the definition of new concepts, such as "low-intervention clinical trial". The legal form of a Regulation allowed the norm to be directly applied to Member States without the need for transposition. By means of the new Royal Decree, the national legislation is adapted to make the application of the regulation feasible and it allows the development of the aspects that the Regulation leaves to national legislation. Both documents seek to stimulate clinical research with medicinal products to foster knowledge, facilitate transparency, and reinforce subjects' safety. This will surely be the case, but with this revision, we will look at the novelties and key aspects that are most relevant to investigators and we will analyse the consequences for all parties involved in clinical research.

Molecular characterization of the RNA-dependent RNA polymerase from groundnut ringspot virus (genus Tospovirus, family Bunyaviridae).

Groundnut ringspot virus is a negative-sense single-stranded RNA virus that belongs to the genus Tospovirus and is the prevalent member of this genus in Brazil. This work presents the nucleotide sequence of the L RNA, with a single open reading frame of 2873 amino acids in the complementary strand corresponding to the RNA-dependent RNA polymerase (L protein), as well as the characterization of conserved domains of the L protein by in silico analysis. Phylogenetic analysis of different L protein domains confirmed that GRSV is a member of the American clade, and comparison with a N-protein indicates that phylogeny based on L protein sequences may be more reliable than that based on the N protein.

Bloqueo AV completo con ritmo de escape idioventricular en un paciente anciano con hiperpotasemia y fibrilación auricular de base / Complete atrioventricular block withidioventricular escape rhythm in elderly patient with hyperpotassemia and baseline atrial fibrillation

Las bradiarritmias son situaciones clínicas frecuentes en pacientes añosos en Atención Primaria. El manejo extrahospitalario de las bradiarritmias, habitualmente con frecuencias cardiacas por debajo de 30 lat/min, puede requerir un tratamiento de urgencia si el paciente presenta síntomas. Los sujetos de edad avanzada están predispuestos a desarrollar una hipercaliemia precipitada, la mayoría de las veces, por fármacos. La hiperpotasemia puede provocar diferentes manifestaciones electrocardiográficas: ondas T picudas, aumento de la amplitud de la onda T, prolongación del intervalo PR y duración del QRS, y alteraciones de la conducción AV. Se expone un caso clínico que ilustra los cambios electrocardiográficos que puede desencadenar una hiperpotasemia y que pueden ser confundidos con signos agudos de cardiopatía isquémica

Bradyarrhythmias are frequent clinical conditions in elderly persons in primary health care. Clinical management of bradycardia outside the hospital, usually with heart beat frequency below 30 beats/minute, may require emergency treatment if the patient has symptoms. Elderly subjects are prone to develop hyperkalemia often caused by drugs. Hyperpotassemia may cause different electrocardiographic manifestations: sharp T-waves, increase in T wave amplitude, PR interval prolongation and widening of QRS complex and atrioventricular conduction alterations. A clinical case is presented that illustrates the electrocardiographic changes that may be caused by hyperpotassemia and that may be confused with acute ischemic heart disease signs

Cerebral ventricles are smaller in Hispanic than non-Hispanic patients with Alzheimer's disease.

MRI scans were compared between 71 Hispanic and 73 white non-Hispanic patients with National Institute of Neurological Disorders and Stroke probable AD. Analysis of covariance controlled for age, sex, education, and Mini-Mental State Examination scores indicated that ventricular size was smaller in Hispanic than white non-Hispanic patients (p = 0.0003). There was no difference in cortical atrophy and T2-weighted white matter hyperintense signals between groups.

[Association of multiple myeloma and solid neoplasms: analysis of 13 cases]. / Asociación de mieloma múltiple y neoplasias sólidas: análisis de trece casos.

BACKGROUND: The diagnosis of second malignancies in patients with multiple myeloma is uncommon. It is debatable whether this tumor is in itself a risk factor for the incidence of second malignancies. Etiopathogenic factors which might account for this association were analyzed. MATERIALS AND METHODS: Retrospective analysis of a series of 210 patients with myeloma controlled by a Medical Oncology Department from 1984 to 1998. After searching for the diagnosis of a second malignancy, thirteen patients were identified with both diagnoses. A descriptive statistical study was elaborated as well as an analysis of survival. RESULTS: There were seven males and six females, with a mean age at diagnosis of 69 years (57-80). The Durie-Salmon stages at diagnosis were: I-A (3), I-B (1), II-A (4), III-A (4). Associated solid malignancies included: hepatocarcinoma (2), prostate adenocarcinoma (2), soft tissue sarcoma (2), lung adenocarcinoma (1), cholangiocarcinoma (1), breast carcinoma (1), endometrial carcinoma (2) and bladder carcinoma (1). At diagnosis, seven of the solid malignancies were metastatic. At the time of this analysis, eleven patients had died, eight because of progression of the solid cancer, two because of progression of myeloma and one because of therapy toxicity. Two patients are still alive with stability of the myeloma and solid malignancy controlled after surgical resection. CONCLUSIONS: The association was observed in 6.2% of patients with myeloma and occurs at an advanced age. IgG myelomas and in early stages predominated. Solid malignancies were diagnosed in advanced stages in most cases. A short term high mortality rate was observed due to progression of the solid malignancy. The frequency of the association did not seem to be higher than the overall incidence of second malignancies in patients with cancer.

[Logistic model for predicting the prognosis in patients with intra-abdominal infection based on the APACHE II index]. / Modelo logístico de predicción del pronóstico en pacientes con infección intraabdominal a partir del índice APACHE II.

BACKGROUND: The APACHE II method has been widely used to classify patients according to disease severity. The high mortality and the lack of reliable prognostic parameters justify the study and application of indexes of severity (IS) and prognostic indexes (PI) in patients with intraabdominal sepsis. METHODS: A prospective study is presented concerning 100 patients with intraabdominal sepsis in whom a prognostic index derived from the APACHE II method by means of a logistic regression model was applied. In this model the APACHE II score is used as the only independent variable with the aim of predicting the outcome (mortality or survival) at the time of hospital admission. RESULTS: The predictive values obtained, with a 70% probability of mortality taken as the cut-off point, were: sensitivity 100%, specificity 87.7% and total predictive capacity 91%. CONCLUSIONS: It was concluded that the logistic prediction model of prognosis shows a high correlation with patient outcome and the application of the APACHE II score is useful in patients with intraabdominal infection.

Necrotising colitis with perforation in diarrhoic patients treated with loperamide.

Two cases of necrotising enterocolitis with perforation occurred in patients with paralytic ileus after loperamide therapy. The possible role of loperamide in the pathogenesis of the complications is suggested.

[Failure of a cyclophosphamide-dexamethasone combination in paraquat poisoning]. / Fracaso de la combinación ciclofosfamida-dexametasona en la intoxicación por paracuat.

A 37-year-old female deliberately ingested a 20% solution of paraquat in water. One hour later gastric lavage was carried out and bentonite was administered. Five hours later cyclophosphamide (5 mg/kg/day) and dexamethasone (24 mg/day) were started and a continuous intestinal lavage was carried out; four hours later, hemodialysis was begun. After 36 hours, features of renal and respiratory failure developed, with a rapid progress to respiratory distress. The patient died 94 hours after the ingestion of the poison. Despite early therapy with dexamethasone and cyclophosphamide, this patient's evolution does not support the presumed effectiveness of this drug association for paraquat poisoning.

Acute renal failure in a patient treated by continuous povidone-iodine mediastinal irrigation.

Polyvinylpyrrolidone-iodine (PI) is a widely used antiseptic agent, safe and effective, in the treatment and prophylaxis of wound sepsis. By continuous irrigation it is frequently used to treat suppurative mediastinitis after median sternotomy. We describe a 63 year old woman with a suppurative mediastinitis, treated with continuous PI irrigation who developed an acute oliguric renal failure. The withdrawal of PI was followed by a complete improvement of renal function. Herein we present our case and a review of the literature about the systemic toxicity of PI.