Management of Patients with Suspected or Confirmed Antibiotic Allergy: Executive Summary of Guidelines from the Spanish Society of Infectious Diseases and Clinical Microbiology (SEIMC), the Spanish Society of Allergy and Clinical Immunology (SEAIC), the Spanish Society of Hospital Pharmacy (SEFH) and the Spanish Society of Intensive Medicine and Coronary Care Units (SEMICYUC).

Suspected or confirmed antibiotic allergy is a frequent clinical circumstance that influences antimicrobial prescription and often leads to the avoidable use of less efficacious and/or more toxic or costly drugs than first-line antimicrobials. Optimizing antimicrobial therapy in patients with antibiotic allergy labels has become one of the priorities of antimicrobial stewardship programs in several countries. These guidelines aim to make recommendations for the systematic approach to patients with suspected or confirmed antibiotic allergy based on current evidence. An expert panel (11 members of various scientific societies) formulated questions about the management of patients with suspected or confirmed antibiotic allergy. A systematic literature review was performed by a medical librarian. The questions were distributed among panel members who selected the most relevant references, summarized the evidence, and formulated graded recommendations when possible. The answers to all the questions were finally reviewed by all panel members. A systematic approach to patients with suspected or confirmed antibiotic allergy was recommended to improve antibiotic selection and, consequently, clinical outcomes. A clinically oriented, 3-category risk-stratification strategy was recommended for patients with suspected antibiotic allergy. Complementary assessments should consider both clinical risk category and preferred antibiotic agent. Empirical therapy recommendations for the most relevant clinical syndromes in patients with suspected or confirmed ß-lactam allergy were formulated, as were recommendations on the implementation and monitoring of the impact of the guidelines. Antimicrobial stewardship programs and allergists should design and implement activities that facilitate the most appropriate use of antibiotics in these patients.

An optimized MNK1b aptamer, apMNKQ2, and its potential use as a therapeutic agent in breast cancer.

Breast cancer is the most commonly diagnosed and leading cause of cancer death among women worldwide. Mitogen-activated protein kinase-interacting kinases (MNKs) promote the expression of several oncogenic proteins and are overexpressed in several types of cancer. In human cells, there are four isoforms of MNKs. The truncated isoform MNK1b, first described in our laboratory, has a higher basal activity and is constitutively active. Aptamers are emerging in recent years as potential therapeutic agents that show significant advantages over drugs of other nature. We have previously obtained and characterized a highly specific aptamer against MNK1b, named apMNK2F, with a dissociation constant in the nanomolar range, which produces significant inhibition of proliferation, migration, and colony formation in breast cancer cells. Furthermore, its sequence analysis predicted two G-quadruplex structures. In this work, we show the optimization process of the aptamer to reduce its size, improving its stability. The obtained aptamer, named apMNKQ2, is able to inhibit proliferation, colony formation, migration, and invasion in breast cancer cells. In murine models of breast cancer, apMNKQ2 has demonstrated its efficacy in reducing tumor volume and the number of metastases. In conclusion, apMNKQ2 could be used as an anti-tumor drug in the future.

Management of Tizanidine Withdrawal Syndrome: A Case Report.

Most drugs that act on the central nervous system (CNS) require dose titration to avoid withdrawal syndrome. Tizanidine withdrawal syndrome is caused by adrenergic discharge due to its α2-agonist mechanism and is characterized by hypertension, reflex tachycardia, hypertonicity, and anxiety. Although tizanidine withdrawal syndrome is mentioned as a potential side effect of cessation, it is not common and there have been few reports. We present the case of a 31-year-old woman with tizanidine withdrawal syndrome after discontinuing medication prescribed for a muscle contracture (tizanidine). She showed high adrenergic activity with nausea, vomiting, generalized tremor, dysthermia, hypertension, and tachycardia. Symptoms were reversed and successful reweaning was achieved by restarting tizanidine followed by slow downward titration. Withdrawal syndrome should be considered when drugs targeting the CNS are suddenly stopped. Weaning regimens should be closely monitored for acute withdrawal reactions.

Liver growth factor induces testicular regeneration in EDS-treated rats and increases protein levels of class B scavenger receptors.

The aim of the present work was to determine the effects of liver growth factor (LGF) on the regeneration process of rat testes after chemical castration induced by ethane dimethanesulfonate (EDS) by analyzing some of the most relevant proteins involved in cholesterol metabolism, such as hormone sensitive lipase (HSL), 3ß-hydroxysteroid dehydrogenase (3ß-HSD), scavenger receptor SR-BI, and other components of the SR family that could contribute to the recovery of steroidogenesis and spermatogenesis in the testis. Sixty male rats were randomized to nontreated (controls) and LGF-treated, EDS-treated, and EDS + LGF-treated groups. Testes were obtained on days 10 (T1), 21 (T2), and 35 (T3) after EDS treatment, embedded in paraffin, and analyzed by immunohistochemistry and Western blot. LGF improved the recovery of the seminiferous epithelia, the appearance of the mature pattern of Leydig cell interstitial distribution, and the expression of mature SR-BI. Moreover, LGF treatment resulted in partial recovery of HSL expression in Leydig cells and spermatogonia. No changes in serum testosterone were observed in control or LGF-treated rats, but in EDS-castrated animals LGF treatment induced a progressive increase in serum testosterone levels and 3ß-HSD expression. Based on the pivotal role of SR-BI in the uptake of cholesteryl esters from HDL, it is suggested that the observed effects of LGF would facilitate the provision of cholesterol for sperm cell growth and Leydig cell recovery.

Use of Subjective Global Assessment, Patient-Generated Subjective Global Assessment and Nutritional Risk Screening 2002 to evaluate the nutritional status of non-critically ill patients on parenteral nutrition.

OBJECTIVE: To evaluate the nutritional status of non-critically ill digestive surgery patients at the moment of parenteral nutrition initiation using three different nutritional test tools and to study their correlation. To study the association between the tests and the clinical and laboratory parameters used in the follow-up of PN treatment. METHODS: Prospective study over 4 months. Anthropometric and clinical variables were recorded. Results of Subjective Global Assessment; Patient-Generated Subjective Global Assessment; and Nutritional Risk Screening 2002 were compared applying kappa test. Relationship between the clinical and laboratory parameters with Subjective Global Assessment was studied by multinominal regression and with the other two tests by multiple linear regression models. Age and sex were included as adjustment variables. RESULTS: Malnutrition in 45 studied patients varied from 51% to 57%. Subjective Global Assessment correlated well with Patient-Generated Subjective Global Assessment and Nutritional Risk Screening 2002 (κ = 0531 p = 0.000). The test with the greatest correlation with the clinical and analytical variables was the Nutritional Risk Screening 2002. Worse nutritional state in this test was associated with worse results in albumin (B = -0.087; CI = -0.169/-0.005], prealbumin (B = -0.005; CI = [-0.011/-0.001]), C-reactive protein (B = 0.006;CI = [0.001/ 0.011]) and leukocytes (B = 0.134; CI = [0.031/0.237]) at the en of parenteral nutrition treatment. CONCLUSIONS: Half of the digestive surgery patients were at malnutritional risk at the moment of initiating parenteral nutrition. Nutritional Risk Screening 2002 was the test with best association with the parameters used in the clinical follow-up of parenteral nutrition treated patients.

Objetivo: Evaluar el estado nutricional de pacientes no críticos de cirugía digestiva, en el momento de iniciar la nutrición parenteral, utilizando tres tests de evaluación nutricional. Estudiar la correlación entre los tests y su asociación con los parámetros clínicos y de laboratorio utilizados para el seguimiento de estos pacientes. Métodos: Estudio prospectivo de 4 meses. Se recogen variables antropométricas y clínicas. Los resultados de Subjective Global Assessment, Patient-Generated Subjective Global Assessment y Nutritional Risk Screening 2002 se comparan mediante test kappa. La relación entre las variables clínicas y de laboratorio con Subjective Global Assessment se estudian con regresión multinominal; y con Patient-Generated Subjective Global Assessment y Nutritional Risk Screening mediante regresión lineal múltiple. Edad y sexo se introdujeron como variables de ajuste. Resultados: La desnutrición en 45 pacientes estudiados variaba entre el 51% y el 57%. Subjective Global Assessment correlacionaba bien con Patient-Generated Subjective Global Assessment y el Nutritional Risk Screening (= 0,531 p = 0,000). Nutritional Risk Screening 2002 mostró mejor asociación con variables clínicas y analíticas: peor estado nutricional en este test se asoció con peor comportamiento de albúmina (B = -0,087; CI = -0,169/-0,005]); prealbumina (B = -0,005; CI = [-0,011/ 0,001]), proteína C reactiva (B = 0,006;CI = [0,001/0,011]) y leucocitos (B = 0,134; CI = [0,031/0,237]) al final de la nutrición parenteral. Discusión: La mitad de los pacientes de cirugía digestiva presentan algún grado de desnutrición en el momento de iniciar la nutrición parenteral. El Nutritional Risk Screening 2002 se mostró como el test con mayor relación con las variables utilizadas en el seguimiento clínico de los pacientes con nutrición parenteral.

Use of Subjective Global Assessment, Patient-Generated Subjective Global Assessment and Nutritional Risk Screening 2002 to evaluate the nutritional status of non-critically ill patients on parenteral nutrition / Utilización de Subjective Global Assessment, patient-generated subjective global assessment y nutritional risk screening 2002 para evaluar el estado nutricional de pacientes no críticos con nutrición parenteral

Objective: To evaluate the nutritional status of non-critically ill digestive surgery patients at the moment of parenteral nutrition initiation using three different nutritional test tools and to study their correlation. To study the association between the tests and the clinical and laboratory parameters used in the follow-up of PN treatment. Methods: Prospective study over 4 months. Anthropometric and clinical variables were recorded. Results of Subjective Global Assessment; Patient-Generated Subjective Global Assessment; and Nutritional Risk Screening 2002 were compared applying kappa test. Relationship between the clinical and laboratory parameters with Subjective Global Assessment was studied by multinominal regression and with the other two tests by multiple linear regression models. Age and sex were included as adjustment variables. Results: Malnutrition in 45 studied patients varied from 51% to 57%. Subjective Global Assessment correlated well with Patient-Generated Subjective Global Assessment and Nutritional Risk Screening 2002 (κ = 0531 p = 0.000). The test with the greatest correlation with the clinical and analytical variables was the Nutritional Risk Screening 2002. Worse nutritional state in this test was associated with worse results in albumin (B = -0.087; CI = -0.169/-0.005], prealbumin (B = -0.005; CI = [-0.011/-0.001]), C-reactive protein (B = 0.006;CI = [0.001/ 0.011]) and leukocytes (B = 0.134; CI = [0.031/0.237]) at the en of parenteral nutrition treatment. Conclusions: Half of the digestive surgery patients were at malnutritional risk at the moment of initiating parenteral nutrition. Nutritional Risk Screening 2002 was the test with best association with the parameters used in the clinical follow-up of parenteral nutrition treated patients (AU)

Objetivo: Evaluar el estado nutricional de pacientes no críticos de cirugía digestiva, en el momento de iniciar la nutrición parenteral, utilizando tres tests de evaluación nutricional. Estudiar la correlación entre los tests y su asociación con los parámetros clínicos y de laboratorio utilizados para el seguimiento de estos pacientes. Métodos: Estudio prospectivo de 4 meses. Se recogen variables antropométricas y clínicas. Los resultados de Subjective Global Assessment, Patient-Generated Subjective Global Assessment y Nutritional Risk Screening 2002 se comparan mediante test kappa. La relación entre las variables clínicas y de laboratorio con Subjective Global Assessment se estudian con regresión multinominal; y con Patient-Generated Subjective Global Assessment y Nutritional Risk Screening mediante regresión lineal múltiple. Edad y sexo se introdujeron como variables de ajuste. Resultados: La desnutrición en 45 pacientes estudiados variaba entre el 51% y el 57%. Subjective Global Assessment correlacionaba bien con Patient-Generated Subjective Global Assessment y el Nutritional Risk Screening (κ = 0,531 p = 0,000). Nutritional Risk Screening 2002 mostró mejor asociación con variables clínicas y analíticas: peor estado nutricional en este test se asoció con peor comportamiento de albúmina (B = -0,087; CI = -0,169/-0,005]); prealbumina (B = -0,005; CI = [-0,011/ 0,001]), proteína C reactiva (B = 0,006;CI = [0,001/0,011]) y leucocitos (B = 0,134; CI = [0,031/0,237]) al final de la nutrición parenteral. Discusión: La mitad de los pacientes de cirugía digestiva presentan algún grado de desnutrición en el momento de iniciar la nutrición parenteral. El Nutritional Risk Screening 2002 se mostró como el test con mayor relación con las variables utilizadas en el seguimiento clínico de los pacientes con nutrición parenteral (AU)

Modulation of calcium channels by taurine acting via a metabotropic-like glycine receptor.

Taurine is one of the most abundant free amino acids in the central nervous system, where it displays several functions. However, its molecular targets remain unknown. It is well known that taurine can activate GABA-A and strychnine-sensitive glycine receptors, which increases a chloride conductance. In this study, we describe that acute application of taurine induces a dose-dependent inhibition of voltage-dependent calcium channels in chromaffin cells from bovine adrenal medullae. This taurine effect was not explained by the activation of either GABA-A, GABA-B or strychnine-sensitive glycine receptors. Interestingly, glycine mimicked the modulatory action exerted by taurine on calcium channels, although the acute application of glycine did not elicit any ionic current in these cells. Additionally, the modulation of calcium channels exerted by both taurine and glycine was prevented by the intracellular dialysis of GDP-ß-S. Thus, the modulation of voltage-dependent calcium channels by taurine seems to be mediated by a metabotropic-like glycinergic receptor coupled to G-protein activation in a membrane delimited pathway.