We report here a 3,698,214-bp complete genome sequence of a potential probiotic Lactobacillus pentosus strain, MP-10, isolated from brines of naturally fermented Aloreña green table olives; it is ...considered the largest sequenced genome among lactobacilli to date. The annotated genome sequence revealed the presence of 3,558 open reading frames (ORFs) and 87 structural RNAs.
Resumen La enfermedad de Crohn (EC) es una enfermedad inflamatoria intestinal (EII) que afecta a cualquier parte del tracto gastrointestinal, en forma de brotes y recidivas. Ustekinumab es un ...anticuerpo monoclonal inhibidor de interleukinas IL-12/23 autorizado para el tratamiento de la EC moderada/grave. Existe un número cada vez mayor de pacientes obesos con EII, que se asocia con peor respuesta al tratamiento biológico, mayor riesgo de recaídas y complejidad en el tratamiento quirúrgico. La cirugía bariátrica, tratamiento eficaz de la obesidad grave que mejora las comorbilidades asociadas, se relaciona con un riesgo elevado en pacientes con EII. El tratamiento de la EII en embarazadas también supone un desafío, que requiere un enfoque multidisciplinar y un control óptimo de la enfermedad tanto antes como durante el embarazo. La ficha técnica de ustekinumab describe datos insuficientes de seguridad durante el embarazo y recomienda evitar su utilización. Este caso clínico aborda el tratamiento de la EC en una paciente obesa y embarazada, dos situaciones especiales en las que el balance beneficio-riesgo resulta fundamental en la toma de decisiones terapéuticas y respecto a las que hace falta un mayor desarrollo de evidencia científica. De los tratamientos biológicos recibidos por la paciente, ustekinumab consiguió mejor respuesta y control de los síntomas de forma segura.
Exotic hadrons made of five quarks (pentaquarks) are searched for in hadronic Z decays collected by the ALEPH detector at LEP. No significant signal is observed. At 95% C.L., upper limits are set on ...the production rates N of such particles and their charge-conjugate state per Z decay: NΘ(1535)+⋅BR(Θ(1535)+→pKS0)<6.2×10−4,NΞ(1862)−−⋅BR(Ξ(1862)−−→Ξ−π−)<4.5×10−4,NΞ(1862)0⋅BR(Ξ(1862)0→Ξ−π+)<8.9×10−4,NΘc(3100)0⋅BR(Θc(3100)0→D*−p)<6.3×10−4,NΘc(3100)0⋅BR(Θc(3100)0→D−p)<31×10−4.
The magnetic and conductive properties of a series of quinoidal oligothiophenes, that is, bis(dicyanomethylene)oligothiophenes (TnCN4, n = 2−4), have been investigated in the solid state and (for ...magnetic analysis) in solution, and the results have been compared with those from density functional theory (DFT) calculations. Solution electron spin resonance (ESR) spectra of radical cations and anions are characterized by hyperfine structures due to coupling with nitrogen and thiophene hydrogen atoms. Neutral solutions are ESR active, indicating a significant presence of diradical species with no hyperfine structure. ESR spectra of powder samples at room temperature give a concentration of radical species up to 1 mol % (T3CN4), that is, 0.5% of the compound exists in a diradical state. The percentage decreases dramatically from T3CN4 to T2CN4, as a result of the decreased number of aromatic rings. The diradical concentration increases with temperature according to activation energies which are higher for the shorter members and in very good agreement with DFT calculations. Tetrahexyl-substituted T4CN4 is redox conducting at the neutral-polaron mixed oxidation level with a maximum conductivity of 0.03 S cm-1, about two orders of magnitude higher in comparison with an aromatic tetrahexyl-substituted octathiophene.
BackgroundAfter the approval of nivolumab some time ago it is necessary to analyse if the results of the randomised clinical trials are correlated with usual clinical practice.PurposeIn this study we ...assessed median progression-free survival, overall survival and safety in patients diagnosed with advanced nonsquamous non-small cell lung cancer who received the second line of treatment with nivolumab monotherapy in our hospital, comparing it with the results of the pivotal trial.Material and methodsA retrospective and descriptive review of patients treated with nivolumab in our centre from January 2016 to September 2018 was done. The patients received 3 mg/kg every 14 days. The following variables were collected from the unified clinical history and the cytostatic management programme: nonsquamous non-small cell lung cancer diagnosis, sex and performance status. The progression-free survival and overall survival curve was constructed using the Kaplan–Meier method, from which the median was obtained and compared to the pivotal trial (CheckMate 057). The main adverse events were collected.ResultsTwenty-five patients were treated in the second line with advanced nonsquamous non-small cell lung cancer with nivolumab of whom 80% was male. Performance status was 0, 1 or 2 in 28%, 68% and 4% patients respectively. Median progression-free survival reached was 5.5 months, which was 3.2 months higher than the trial (2.3 months). Median overall survival reached was 12 months which was 0.2 months lower than the trial (12.2 months). The most prevalent adverse events were asthaenia (44%), nausea (20%) and diarrhoea (12%). There were two patients with grade 3 asthaenia, one patient with alanine aminotransferase increased grade 3 and one patient with pneumonitis.ConclusionThe effectiveness obtained measured with median progression-free survival was higher than that of the pivotal trial, and analogous measured as overall survival, however we must take into account the limitations of a study with a low number of patients. A small percentage of patients present adverse events grade 3.References and/or acknowledgementsNo conflict of interest.
BackgroundIn clinical practice, dimethylfumarate is considered an alternative at the level of conventional systemic drugs in the first line (cyclosporine, methotrexate, acitretin) for ...moderate-to-severe plaque psoriasis (PP).PurposeTo establish whether dimethylfumarate, methotrexate, cyclosporine and acitretin can be considered equivalent therapeutic alternatives (ATE) in efficacy in PP.Material and methodsWe conducted a search of clinical trials of these drugs, phase III, double-blind, controlled with methotrexate or placebo, efficacy evaluated at 12 weeks or next, adults diagnosed with PP and uncontrolled disease with topical treatments and/or phototherapy. The 75% reduction in the Psoriasis Area and Severity index was used as the main variable (PASI75). An indirect comparison (IC) of cyclosporin versus fumarates and dimethylfumarate versus methotrexate was performed using the Bucher method, using the Indirect Treatment Comparisons calculator from the Canadian Agency for Health Technology Assessment. For cyclosporine with more than one published study, a previous meta-analysis was performed (Der Simonian–Laird method), using the Joaquin Primo calculator. Considering that the failure can be recovered with an effective second line, it was taken as delta value, for PASI75 the value in previous published studies of IC of biological in PP, 15%. The results were analysed graphically and the relative position of the 95% CI and the equivalence margin were observed. To establish the positioning, the ATE Guide was followed.ResultsIncluded four clinical trials, two of ciclosporin, one of dimethylfumarate and one of fumarates. The acitretin studies were excluded because they did not meet the inclusion criteria. The difference in PASI75 expressed as RAR (IC95%) of methotrexate versus dimethylfumarate, and ciclosporin versus fumarates, was: 2.2% (-22,2;26,6) y 17 (-14,83;48,83). Applying the ATE Guide, methotrexate and dimethylfumarate can be declared ATE, being the probability of clinically relevant difference <50% (most of the 95% CI is in the equivalence range) and the failure does not involve serious/irreversible damage. Cyclosporine and fumarates could not be considered ATE (the RAR exceeded the delta with more than 50% probability so that the difference was clinically relevant).ConclusionDimethylfumarate and methotrexate could be considered ATE. Ciclosporin and fumarates could not be considered ATE. For a definitive statement of ATE, the criteria of safety and adequacy should be considered.References and/or acknowledgementsNo conflict of interest.
BackgroundTo date, the main treatment in advanced breast cancer (ABC) with BRCA mutation is a non-specific chemotherapy of the physician’s choice.PurposeTo establish whether olaparib and talazoparib ...can be declared equivalent therapeutic alternatives (ETA) in patients with ABC and a BRCA mutation, through an indirect treatment comparison (ITC) using a common comparator.Material and methodsA bibliographic search was conducted to identify a phase III clinical trial with olaparib or talazoparib in a similar ABC population (with BRCA mutation), duration and endpoints. An ITC was done according to Bucher’s method, using the ITC calculator from the Canadian Agency for Health Technology Assessment. Physician’s choice (capecitabine, eribulin or vinorelbine) was used as a comparator. Delta value (Δ), maximum acceptable difference as a clinical criterion of no-inferiority, was set at 0.650 (and its inverse, 1.538). If the 95% CI deviated from the delta margin, this probability was calculated using the Shakespeare method.ResultsClinical trials included were: open-label, randomised, HER 2-negative, capecitabine, eribulin or vinorelbine as comparator, ECOG 0–1, pretreated with taxane, anthracycline or both, and if platinum was used without progression to this one. The primary end point was radiologic progression-free survival (PFS). Two trials were included, one of each drug. Both of them were open-label trials, randomised, in patients with HER2-negative ABC, ECOG 0–1 and pretreated with taxane, anthracycline or both. Differences were found in the percentage of patients with ECOG 0–1 (olaparib 72.2% vs. talazoparib 53.3%), excepting this characteristic the population of both studies was similar. The results of each trial, as well as the ITC conducted, are summarised in the following table 1:Abstract 2SPD-009 Table 1ReferencePFS: HR (95% CI) Olaparib0.58 (0.43–0.80)Talazoparib0.54 (0.41–0.71)ITC1.074 (0.71–1.626)The 95% CI was broad (high level of uncertainty) and exceeds the equivalence margin, and the probability of a result falling out the delta margin was <4.5%.ConclusionITC showed no statistically differences in PFS between olaparib and talazoparib.There is a probable clinical equivalence between both drugs. Although a fraction crosses the confidence interval, this is not statistically significant.Olaparib and talazoparib could be considered as ETA in most patients with advanced breast cancer.References and/or acknowledgementsNo conflict of interest.
BackgroundDue to the recent commercialisation of the presentations of Tenofovir Alafenamide (TAF) for HIV, there is a need to analyse the costs involved in its introduction into the public health ...system and its potential impact.PurposeThe objective of the study is to assess the cost of using TAF instead of tenofovir-disoproxil fumarate (TDF) in a public health hospital.Material and methodsA retrospective and descriptive study of all the patients who used TDF in their HIV treatment regimens from January 2018 to October 2018 was done. Data of the different treatment regimens for HIV containing TDF and adherence to treatment were collected. The TDF treatments regimens were replaced by their commercial equivalent with TAF and the hospital acquisition prices were compared. The cost for each patient was calculated according to TDF or TAF presentation and extrapolated to one year of treatment. The sources of information were the outpatient database and management of the hospital pharmacy service.ResultsDuring the study period, 204 patients used TDF in their treatment regimen for HIV: 151 patients used TDF +emtricitabine + elvitegravir, 16 patients used TDF +emtricitabine + darunavir/cobicistat and 37 used TDF +emtricitabine + another third drug. The adherence to the treatment was 95%. The patient cost and its annual potential cost are summarised in the following table 1:Abstract 2SPD-005 Table 1 N° patients Patient cost Annual cost Difference TDF+emtricitabine+elvitegravir151€560,22€1,015,118.64TAF+emtricitabine+elvitegravir151€726€1,315,512€300,393.36TDF+emtricitabine+darunavir/cobicistat16€380,65€73,084.8TAF+emtricitabine+darunavir/cobicistat16€918€1 76 256€103,171.2TDF+emtricitabine+3° fármaco (not study)37€31.2€13,852.8TAF+emtricitabine+3° fármaco (not study)37€314.3€139.549.2€125,696.4ConclusionAlmost 75% of patients with TDF used a treatment regimen with emtricitabine +elvitegravir. Adherence to the treatment was excellent. The consideration to switch TDF to TAF must take into account its associated cost due to the high impact that would imply.References and/or acknowledgementsNo conflict of interest.
Bose–Einstein correlations in W-pair decays are studied using data collected by the ALEPH detector at LEP at e+e− centre-of-mass energies from 183 to 209 GeV. The analysis is based on the comparison ...of WW→qq¯qq¯ events to “mixed” events constructed with the hadronic part of WW→qq¯ℓν events. The data are in agreement with the hypothesis that Bose–Einstein correlations are present only for pions from the same W decay. The JETSET model with Bose–Einstein correlations between pions from different W bosons is disfavoured.
Resumen La arteritis de Takayasu (AT) es una enfermedad rara descrita como una vasculitis granulomatosa que afecta a las arterias elásticas de gran calibre, fundamentalmente la aorta y sus ramas ...principales. Como consecuencia de la inflamación de estos grandes vasos, puede dar lugar a la formación de aneurismas, estenosis u oclusión vascular. Afecta principalmente a mujeres jóvenes y los síntomas incluyen: síncope, mareo, disminución o ausencia de pulso, y alteración de la visión. El tratamiento convencional se basa principalmente en la utilización de corticoides e inmunosupresores, aunque recientemente se ha comenzado a considerar el uso de fármacos biológicos. Tocilizumab es un anticuerpo monoclonal dirigido contra IL-6 utilizado fuera de ficha técnica en algunos pacientes para tratar esta patología. Presentamos dos casos clínicos que describen el uso a largo plazo de tocilizumab en pacientes con AT refractaria al tratamiento convencional. En ambos casos se observó una excelente respuesta a tocilizumab, con remisión de la sintomatología y reducción de las dosis de corticoides asociados. No se registraron eventos adversos asociados al tratamiento.
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