Filgotinib as rheumatoid arthritis therapy.

Rheumatoid arthritis (RA) is a chronic autoimmune disease characterized by joint inflammation and progressive disability when inflammation cannot be sufficiently controlled. Despite treatment with conventional synthetic disease-modifying antirheumatic drugs (csDMARDs) and biological DMARDs (bDMARDs), up to 30% of RA patients do not reach or fail to maintain a good response over time. The recent introduction of Janus kinase inhibitors (JAKis) has widened the rheumatologist's armamentarium. Filgotinib, a selective JAK1 inhibitor, has been approved by the European Medicines Agency (EMA) for treatment of RA. Phase II and III studies highlighted filgotinib safety and efficacy in RA patients naive to DMARDs or with inadequate response to csDMARDs and bDMARDs. Filgotinib is administered orally at 200 mg every day. For patients older than 75 years or with moderate to severe renal impairment, a dose of filgotinib 100 mg every day is recommended.

Internal medicine inpatients' prevalence of misdiagnosed severe osteoporosis.

Vertebral fractures (VF) related to osteoporosis (i.e., severe OP) increase the risk of disability and mortality, but they are often neglected. We observed a severe OP misdiagnosis in 28.9% of inpatients with previous spinal imaging positive for VFs. Diagnosing severe OP is crucial to reduce the health care costs of inpatients. INTRODUCTION: Vertebral fractures (VFs) related to osteoporosis (OP) increase the risk of additional fractures and death. In inpatients, VFs are often neglected with consequent delay in OP treatments, prolongation of hospitalization, and reduction of life expectancy. The aim of this study was to evaluate the prevalence of a misdiagnosed severe OP (i.e., with VF) in general medicine inpatients. METHODS: We evaluated inpatients of a Medicine Unit between January 2019 and December 2019 without severe OP diagnosis, who had spinal imaging. For each patient, we collected demographic data, previous or current OP treatment, and presence/number of VFs. Descriptive data were presented by medians (interquartile range [IQR]) for continuous data or as numbers (percentages) for categorical data. Differences between subgroups were analyzed with chi-square or Kruskal-Wallis tests as appropriate. p-values <0.05 were considered statistically significant. RESULTS: 793 subjects were admitted to inpatient's clinic: 235 (135 females and 100 males with a median age of 76.0 [64.0-83.0] years) were enrolled. One or more vertebral fractures were present in 28.9% (68/235) subjects; 47% (32/68) had two or more vertebral fractures. The majority of patients (55/68) with VFs had not previously received a severe OP diagnosis. CONCLUSIONS: Severe OP was misdiagnosed in at least 8.6% of inpatients. The prevalence dramatically increases (about 29%) in subjects with previous spinal imaging showing one or more VFs. More attention should be given to this co-morbidity, which is known to be an additional risk factor for disability and mortality.

¿Cómo fijamos el tubo endotraqueal en la unidad de cuidados intensivos pediátricos? / How to secure the endotracheal tube in the pediatric intensive care unit?

Introducción: Las extubaciones no planeadas son eventos adversos frecuentes en áreas críticas de pediatría. La técnica y el material para llevar a cabo la fijación condicionan la aparición de estos eventos adversos. La evidencia científica que evalúe factores es escasa. Objetivos: El objetivo principal de este trabajo fue obtener datos concretos al respecto de las prácticas de los enfermeros en la fijación del tubo endotraqueal (TET) e identificar técnicas. Métodos: Estudio de carácter descriptivo y prospectivo. Se encuestaron 125 enfermeros de las diferentes Unidades de Cuidados Intensivos durante el mes de noviembre de 2016. Resultados: El 88% de los enfermeros basan su método en la utilización de cinta adhesiva. La técnica de fijación de 3 tiras prevalece por encima de las demás (64%). No existen grandes preferencias al respecto del tipo de cinta adhesiva, no obstante, el 22% menciona a la cinta de óxido de zinc. La alternativa de fijación en niños quemados muestra a la venda de tela como una opción (42%). El 27% de los enfermeros consultados coincidió en que no existe una técnica ideal ya que esta va a depender de la circunstancia clínica del niño. Las complicaciones asociadas a la fijación inadecuada son en primer lugar el desplazamiento por introducción (54%) y la extubación (31%). Conclusión: Se evidencia una amplia variedad de criterios al momento de llevar a cabo la técnica de fijación de TET. Finalmente podemos concluir en que los métodos de fijación dependerán exclusivamente de las características clínicas del niño, el criterio del operador y los recursos disponibles en cada institución (AU)

Introduction: Unplanned extubations are frequent adverse events in critical care in pediatrics. The technique of endotracheal tube (ETT) fixation and the materials affect the appearance of these adverse events. Studies that evaluate these factors are scarce. Objectives: The main aim of this study was to collect data on the practices of nurses in the fixation of the ETT and to identify techniques. Methods: A prospective, descriptive study was conducted. A survey was administered to 125 nurses from different Intensive Care Units in November 2016. Results: 88% of the nurses use tape to secure the ETT. The method of fixation with three strips was the most widely used (64%). There was no preference on the type of tape used; however, 22% preferred to use zinc oxide tape. In burned patients an alternative method with a cloth bandage was used (42%). Overall, 27% of the nurses surveyed coincided that an ideal method to secure the ETT is lacking, as this depends on the clinical circumstances of the child. Complications associated with inadequate tube fixation are displacement during fixation (54%) and la extubation (31%). Conclusion: A wide variety of criteria is used in the techniques to secure the ETT. Finally, we may conclude that fixation methods depend exclusively on the clinical characteristics of the child, criteria of the operator, and resources available at the institution (AU)

Compensatory RNA polymerase 2 loading determines the efficacy and transcriptional selectivity of JQ1 in Myc-driven tumors.

Inhibition of bromodomain and extraterminal motif (BET) proteins such as BRD4 bears great promise for cancer treatment and its efficacy has been frequently attributed to Myc downregulation. Here, we use B-cell tumors as a model to address the mechanism of action of JQ1, a widely used BET inhibitor. Although JQ1 led to widespread eviction of BRD4 from chromatin, its effect on gene transcription was limited to a restricted set of genes. This was unlinked to Myc downregulation or its chromatin association. Yet, JQ1-sensitive genes were enriched for Myc and E2F targets, were expressed at high levels, and showed high promoter occupancy by RNAPol2, BRD4, Myc and E2F. Their marked decrease in transcriptional elongation upon JQ1 treatment, indicated that BRD4-dependent promoter clearance was rate limiting for transcription. At JQ1-insensitive genes the drop in transcriptional elongation still occurred, but was compensated by enhanced RNAPol2 recruitment. Similar results were obtained with other inhibitors of transcriptional elongation. Thus, the selective transcriptional effects following JQ1 treatment are linked to the inability of JQ1-sensitive genes to sustain compensatory RNAPol2 recruitment to promoters. These observations highlight the role of BET proteins in supporting transcriptional elongation and rationalize how a general suppression of elongation may selectively affects transcription.

Microwave-assisted fluorolytic sol-gel route to iron fluoride nanoparticles for Li-ion batteries.

A simple microwave-assisted fluorolytic sol-gel synthesis of 30 nm sized FeF3 nanocrystals supported on partially reduced graphene oxide is reported. The as-fabricated nanostructures used as positive electrodes in Li-ion batteries show capacity retention as high as 150 mA h g(-1) even after having sustained repeated charge-discharge cycles.

Room-temperature hydrogen sensing with heteronanostructures based on reduced graphene oxide and tin oxide.

There's something in the air … A nanocomposite consisting of well-dispersed SnO(2) and Pt nanoparticles on reduced graphene oxide (see the high-resolution TEM image) exhibited very high responses to hydrogen at concentrations between 0.5 and 3% in air, with response times of 3-7 s and recovery times of 2-6 s. The sensor was prepared by a straightforward microwave-assisted non-aqueous sol-gel approach.

Espectrofotometria derivada: uma contribuição prática para o desenvolvimento de métodos / A contribution to the derivative spectrophotometry method

A espectrofotometria derivada (ED) tem sido utilizada como uma importante ferramenta no controle de qualidade de medicamentos para a determinação simultânea de fármacos em sistemas multicomponentes. Esta técnica oferece uma alternativa para melhorar a sensibilidade e a seletividade na análise de misturas e está acessível à maioria dos laboratórios. O procedimento é simples, rápido e não necessita extração prévia da amostra. Este trabalho tem como objetivo fornecer subsídios para o desenvolvimento de método por espectrofotometria derivada, utilizando a técnica do ponto de anulação, visando utilizá-la como um método alternativo no controle de qualidade de fármacos associados e, em especial, nos estudos de dissolução. Muitos subsídios foram retirados da literatura, outros de experiências vivenciadas no laboratório durante o desenvolvimento do método por ED aplicado na análise de dois inibidores da protease do vírus da imunodeficiência humana. Várias ordens de derivadas, diferentes valores de lambda delta e diferentes velocidades de varredura foram avaliados.

Derivative spectrophotometry has been successfully used as a quality control tool in pharmaceutical analysis for the simultaneous determination of drugs in multicomponent formulations. This technique, accessible to most laboratories, offers an alternative means of enhancing the sensitivity and specificity in mixture analysis. The procedure is simple, rapid and does not require any preliminary separations or treatment of the samples. The aim of this study is to provide pointers for the development of methods of analysis by derivative spectrophotometry (DS), using the zerocrossing technique, and to encourage professionals and researchers to use DS as an alternative method for quality control of drug combinations, especially in the study of dissolution. Much information, extracted from the literature, has been assembled here, together with the laboratory experience gained while developing a DS method to analyze a combination of two human immunodeficiency virus protease inhibitors. Various orders of derivatives, values of delta lambda and scan speeds were tested.

Effect of addition of rituximab to salvage chemotherapy on outcome of patients with diffuse large B-cell lymphoma relapsing after an autologous stem-cell transplantation.

BACKGROUND: We have investigated if rituximab-based salvage regimens improve response rates and survival of patients with diffuse large B-cell lymphoma (DLBCL) relapsing after an autologous stem-cell transplantation (ASCT). PATIENTS AND METHODS: We have retrospectively analyzed 82 patients with DLBCL who received salvage therapy for relapse or progression after ASCT. Patients were divided into two groups, according to whether rituximab-based salvage regimens were given (n = 42, 'R-' group) or not (n = 40, 'R+' group) after ASCT. RESULTS: Patients in the R+ group had better complete remission (CR) (55% versus 21.4%, P = 0.006) and overall response (OR) (75% versus 40.4%, P = 0.001) rates, and better 3-year event-free survival (EFS) (37% versus 9%, P = 0.002) and overall survival (OS) (50% versus 20%, P = 0.005) than patients in the R- group. Patients retreated with rituximab had better CR (42.9% versus 21.4%, P = 0.032) and OR (66.7% versus 40.4%, P = 0.019) rates, and better OS (36.2% versus 20% at 3 years, P = 0.05) and EFS (36.2% versus 9% at 3 years, P = 0.05) than patients who received chemotherapy alone at relapse after ASCT. CONCLUSIONS: The addition of rituximab to salvage chemotherapy improves response rates and EFS in patients with relapsed DLBCL after ASCT. These patients may benefit from rituximab retreatment, although larger prospective studies are needed to confirm these results.

Cyclin E expression in breast cancer: predicting germline BRCA1 mutations, prognosis and response to treatment.

BACKGROUND: Elevated levels of the cell cycle protein cyclin E, and low levels of its inhibitor, p27(Kip1), have been associated with a poor prognosis following breast cancer. Some studies have found that germline mutations in the breast cancer susceptibility gene, BRCA1, are also associated with an inferior survival rate. The relationship between cyclin E/p27(Kip1) levels, BRCA1 status and outcome has not been studied in detail. PATIENTS AND METHODS: We analyzed a historical cohort of 288 Ashkenazi Jewish women who were diagnosed with breast cancer between 1980 and 1995 and were previously tested for BRCA1/2 mutations. Protein levels of cyclin E and p27(Kip1) were assessed by immunohistochemistry. Breast cancer-specific survival (BCSS) was the main outcome measured. RESULTS: The median follow-up was 8 years. Thirty tumors carried germline BRCA1 mutations. These tumors were more likely to have high cyclin E protein levels [odds ratio (OR) 9.5; P <0.001] and low p27(Kip1) protein levels (OR 2.8; P=0.03) than tumors from patients without BRCA1/2 mutations. High cyclin E expression level was the strongest predictor of BRCA1 germline mutations (multivariate OR 4.7; P=0.004). On univariate analysis, high cyclin E protein levels [relative risk (RR) 2.6; P <0.001] and low p27(Kip1) protein levels (RR 2.3; P=0.006) were significant prognostic factors for a poorer BCSS. In Cox multivariate models, high cyclin E levels remained an independent indicator of poor outcome only in the subgroup of patients who did not receive chemotherapy (P=0.002). CONCLUSIONS: In this ethnically restricted cohort, a high level of cyclin E is a characteristic of BRCA1-related breast cancer, and is a marker of poor prognosis following breast cancer, particularly in the absence of adjuvant chemotherapy.

[Experience on the pancreatic function after an episode of acute biliary oedematous pancreatitis]. / Studio sulla possibile alterazione della funzionalità pancreatica dopo un episodio di pancreatite acuta biliare edematosa.

The authors have examinated 35 patients 4 - 5 years after a previous episode of acute oedematous biliary pancreatitis. 20 patients had been cholecystectomized while 15 had not been operated. The patients of the first group didn't show any impairment of the endocrine or exocrine pancreatic function while the patients who were not cholecystectomized in 4 cases on 15 showed an impairment of the exocrine pancreatic function valued with the elastase-1 test in the stools. In 2 patients there was also a slight impairment of the glucose metabolism. The authors suppose that the persistance of a biliary disease can affect the pancreatic function.

The Quality of Life Profile--Adolescent Version: background, description, and initial validation.

PURPOSE: Emerging concepts of adolescent health were considered within a broadened quality of life perspective. Instrumentation examining quality of life-the extent to which a person enjoys the important possibilities of his/her life-in three broad domains of adolescent functioning: being, belonging, and becoming, was developed and validated. METHODS: The 54-item Quality of Life Profile: Adolescent Version (QOLPAV) asks adolescents to rate items for importance and satisfaction. The QOLPAV was administered, together with a range of other measures of adolescent functioning, to 160 Canadian adolescents. RESULTS: QOLPAV scores were reliable and correlated with measures of adolescent personality, self-reported health status, and tobacco and alcohol use. CONCLUSIONS: With further validation, the QOLPAV could be used to assess current states of coping and functioning, identify adolescents' service needs, develop health enhancing environments, and assess the effects of illness and treatments.