Low-Dose Rituximab for Bullous Pemphigoid. Protocol and Single-Center Experience.

BACKGROUND: Low-dose rituximab is a protocol used in several autoimmune diseases, that has also shown to be effective and safe in pemphigus vulgaris. OBJECTIVES: To study whether low-dose rituximab is also effective for bullous pemphigoid. METHODS: Patients with BP were treated with a single cycle of two infusions of rituximab 500mg at an interval of 2 weeks. Early and late end points were monitored. RESULTS: Six patients, five males and a female, with a mean age of 78.6 years (range 65-89) and a mean history of BP of 6.7 months (range 2-16) were included. A rapid and marked response was observed after a single cycle of treatment, with a mean time to disease control and to end of consolidation phase of 1.9 (range 1-3), and 4 weeks (range 3-5), respectively. Four patients achieved a late end point at a mean of 15.75 weeks (range 13-20). Three of them achieved partial remission with no therapy (two patients) or with minimal therapy (one patient), and one of them achieved complete remission with no therapy. One patient has 6 weeks of clinical follow-up after rituximab administration. The remaining patient relapsed 4 weeks after the rituximab treatment, and remains in complete remission with more than minimal therapy. One patient had a herpetic gingivostomatitis related to rituximab. CONCLUSIONS: Low-dose rituximab for BP achieved acceptable remission rates and steroid-sparing activity, with a better safety profile and a lower cost, compared to standard doses. This pilot study suggests that low-dose rituximab could be a therapeutic option for BP.

Low-Dose Rituximab for Bullous Pemphigoid. Protocol and Single-Center Experience. / [Artículo traducido] Baja dosis de rituximab para penfigoide ampolloso. Protocolo y experiencia de un único centro.

BACKGROUND: Low-dose rituximab is a protocol used in several autoimmune diseases, that has also shown to be effective and safe in pemphigus vulgaris. OBJECTIVES: To study whether low-dose rituximab is also effective for bullous pemphigoid. METHODS: Patients with BP were treated with a single cycle of two infusions of rituximab 500 mg at an interval of 2 weeks. Early and late end points were monitored. RESULTS: Six patients, five males and a female, with a mean age of 78.6 years (range 65-89) and a mean history of BP of 6.7 months (range 2-16) were included. A rapid and marked response was observed after a single cycle of treatment, with a mean time to disease control and to end of consolidation phase of 1.9 (range 1-3), and 4 weeks (range 3-5), respectively. Four patients achieved a late end point at a mean of 15.75 weeks (range 13-20). Three of them achieved partial remission with no therapy (two patients) or with minimal therapy (one patient), and one of them achieved complete remission with no therapy. One patient has 6 weeks of clinical follow-up after rituximab administration. The remaining patient relapsed 4 weeks after the rituximab treatment, and remains in complete remission with more than minimal therapy. One patient had a herpetic gingivostomatitis related to rituximab. CONCLUSIONS: Low-dose rituximab for BP achieved acceptable remission rates and steroid-sparing activity, with a better safety profile and a lower cost, compared to standard doses. This pilot study suggests that low-dose rituximab could be a therapeutic option for BP.

Phase stability of dispersions of hollow silica nanocubes mediated by non-adsorbing polymers.

Although there are theoretical predictions (Eur. Phys. J. E 41, 110 (2018)) for the rich-phase behaviour of colloidal cubes mixed with non-adsorbing polymers, a thorough verification of this phase behaviour is still underway; experimental studies on mixtures of cubes and non-adsorbing polymers in bulk are scarce. In this paper, mixtures of hollow silica nanocubes and linear polystyrene in N,-N-dimethylformamide are used to measure the structure factor of the colloidal cubes as a function of non-adsorbing polymer concentration. Together with visual observations these structure factors enabled us to assess the depletion-mediated phase stability of cube-polymer mixtures. The theoretical and experimental phase boundaries for cube-depletant mixtures are in remarkable agreement, despite the simplifications underlying the theory employed.

Extra-pulmonary tuberculosis: a biomarker analysis.

INTRODUCTION: Studies on biomarkers in tuberculosis are focused on pulmonary forms of this disease (PTB), and only limited information is currently available on biomarkers of extra-pulmonary tuberculosis (EPTB). METHODS: Serum samples from 24 patients with PTB, 29 patients with EPTB and 27 healthy controls were obtained, and the levels of interferon-gamma, chemokine ligand 9, mannose-binding lectin (MBL), tumor marker Ca-125 and adenosine deaminase were determined. RESULTS: The circulating levels of all tested biomarkers in the serum were significantly higher in PTB and EPTB patients than in controls. However, there were no significant differences in the levels of the biomarkers between patients with PTB and EPTB, with the exception of serum levels of MBL which were significantly higher in patients with EPTB than in patients with PTB (p = 0.01). In patients with EPTB, no significant differences were observed in biomarker levels among patients with or without concomitant PTB involvement. Based on MBL serum levels, ROC curve analysis showed an AUC of 0.85 for EPTB versus non-EPTB. The optimal cut-off value of MBL serum levels for EPTB versus non-EPTB was 1,000 µg/ml, with a sensitivity and specificity of 79.3 and 78.0 %, respectively. CONCLUSIONS: Biomarkers usually present as acute phase reactants and do not enable pulmonary forms to be differentiated from more serious or extra-pulmonary forms. MBL may be an exception.

[Neuroimaging follow-up of cerebral aneurysms treated with endovascular techniques]. / Seguimiento mediante técnicas de neuroimagen de los aneurismas cerebrales tratados por vía endovascular.

There are no specific recommendations in clinical guidelines about the best time, imaging tests, or intervals for following up patients with intracranial aneurysms treated with endovascular techniques. We reviewed the literature, using the following keywords to search in the main medical databases: cerebral aneurysm, coils, endovascular procedure, and follow-up. Within the Cerebrovascular Disease Group of the Spanish Society of Neuroradiology, we aimed to propose recommendations and an orientative protocol based on the scientific evidence for using neuroimaging to monitor intracranial aneurysms that have been treated with endovascular techniques. We aimed to specify the most appropriate neuroimaging techniques, the interval, the time of follow-up, and the best approach to defining the imaging findings, with the ultimate goal of improving clinical outcomes while optimizing and rationalizing the use of available resources.

Executive summary on the optimization of the multidisciplinary and integrated approach to polymyalgia rheumatica and giant cell arteritis in Madrid region.

Polymyalgia rheumatica and giant cell arteritis can be a medical emergency in which a delay in correct diagnosis and therapeutic management can cause serious complications. With the aim of improving the care of patients with these pathologies in the Community of Madrid, a study was designed to identify the causes and possible solutions to address the problems related to the diagnosis of these pathologies. After the analysis, 11 areas of improvement related to four different aspects of the care process were identified: coordination and protocols, equipment, training and awareness of pathologies, and patient experience. Of all the areas identified, it was considered a priority to resolve those related to the generation of protocols for the comprehensive management of the pathologies, which include all the specialties and levels of care involved. Another crucial aspect is the increase in the degree of clinical suspicion of these pathologies.

Treatment of systemic lupus erythematosus: new therapeutic options.

Systemic lupus erythematosus (SLE) is a systemic autoimmune inflammatory disease of unknown cause, with heterogeneity in its clinical presentation, as well as variability in its clinical course and prognosis. The current goal of treatment is to achieve disease remission or a state of low activity, and thereby improve the patient's quality of life. Biological therapy in lupus, unlike other entities, although it has not been fully established, in recent years it has burst onto the scene with important therapeutic novelties. This review aims to update the therapeutic tools for the treatment of SLE focusing on the new molecules that have achieved the objectives of their clinical trials.

[Multidrug resistant narcolepsy]. / Narcolepsia multirresistente.

INTRODUCTION: Narcolepsy type 1 is a focal degenerative disease of the hypothalamus that selectively affects orexin (hypocretin)-producing neurons. It presents multiple clinical manifestations, both in wakefulness and in sleep. The symptoms are often so disruptive that they cause enormous suffering and impair patients' quality of life. Although a non-pharmacological approach is sometimes sufficient, the vast majority of patients need medication for adequate clinical management. CASE REPORT: A male who, at 43 years of age, began to present acutely with excessive daytime sleepiness and episodes of cataplexy. After a thorough examination, he was diagnosed with narcolepsy type 1. Throughout the course of the disease, he was prescribed antidepressants, neurostimulants and sodium oxybate, in monotherapy or in combination. The response to pharmacological treatment was insufficient and accompanied by numerous side effects. Following the introduction of pitolisant, there was a marked improvement in his symptoms and a reduction in the dose of the other drugs and their adverse effects was achieved. CONCLUSION: A number of measures are now available to address the cardinal symptoms of the disease, although there are still cases that are resistant to anti-narcoleptic treatment. Drugs with mechanisms of action that act upon receptors in the histaminergic system can be very useful in these cases.

TITLE: Narcolepsia multirresistente.Introducción. La narcolepsia de tipo 1 es una enfermedad degenerativa focal del hipotálamo que afecta selectivamente a las neuronas productoras de orexina (hipocretina). Presenta múltiples manifestaciones clínicas, tanto en vigilia como en sueño. Con frecuencia, los síntomas son tan disruptivos que ocasionan enorme sufrimiento y deterioro de la calidad de vida de los pacientes. Aunque en ocasiones es suficiente con un abordaje no farmacológico, la gran mayoría de los enfermos necesita medicación para un adecuado control clínico. Caso clínico. Varón que a los 43 años comenzó a presentar de forma aguda excesiva somnolencia diurna y episodios de cataplejía. Tras un exhaustivo estudio se le diagnosticó narcolepsia de tipo 1. A lo largo de la evolución de la enfermedad se le prescribieron antidepresivos, neuroestimulantes y oxibato sódico, en monoterapia o en combinación. La respuesta al tratamiento farmacológico fue insuficiente y se acompañó de numerosos efectos secundarios. Tras la introducción de pitolisant se objetivó una franca mejoría de los síntomas, y se consiguió reducir la dosis de los otros fármacos y de sus efectos adversos. Conclusión. Son numerosas las medidas disponibles en la actualidad para abordar los síntomas cardinales de la enfermedad, aunque siguen existiendo casos resistentes al tratamiento antinarcoléptico. Los fármacos con mecanismos de acción sobre receptores del sistema histaminérgico pueden resultar de gran utilidad en estos casos.

Raman-induced polarization stabilization of vector solitons in circularly birefringent fibers.

Vector soliton propagation in circularly birefringent fibers was studied by perturbation analysis and numerically. The results show that in presence of both Raman self-frequency shift and group velocity difference between circularly polarized components the Raman cross-polarization term causes an energy transfer from the slower to the faster circular component of vector solitons. This effect leads to polarization stabilization of circularly polarized vector solitons.

[Filter content after carotid angioplasty and stenting: relation to ischemic lesions in diffusion-weighted imaging]. / Contenido en filtros tras angioplastia y colocación de stent carotídeo: relación con lesiones isquémicas en la resonancia magnética de difusión.

OBJECTIVES: To evaluate the relation between the material retrieved from distal filters after carotid angioplasty and stenting and the development of ischemic brain lesions in diffusion-weighted imaging (DWI). To determine the influence of demographic, clinical, and procedural variables in the pathogenesis of emboli and in ischemia after carotid angioplasty and stenting. MATERIAL AND METHODS: We submitted the contents of the filters of 76 patients (60 men; mean age, 68.39 years; range, 46-82) who had undergone angioplasty and stenting for severe stenosis of the internal carotid artery for histologic analysis evaluating volume (< 1 λ = 0.001 ml = 1 µl; 1-10 λ; and > 10 λ) and the composition of the particles. All patients underwent DWI before and 24 hours after the procedure; we recorded whether lesions appeared and their number, size, and distribution. We correlated the findings with demographic, clinical, and procedural variables. RESULTS: Symptoms were present before the procedure in 58 (76.3%) patients. Particles were present in 49 (64.5%) of the filters; most particles (77.5%) were 1 λ with a predominance of fibrin-platelet aggregates, cell remnants, and cholesterol crystals. DWI after the procedure detected lesions in 12 (15.8%) patients. We found no statistically significant correlation between filter contents and lesion detection after the procedure or between filter contents and other variables. CONCLUSIONS: Ischemia after carotid angioplasty and stenting does not depend solely on the embolic load and its nature. We consider that the lower prevalence of postprocedural lesions in our series compared to others suggests that appropriate patient selection and experience minimize the negative influence of some variables like age in their development.

Transition-metal adatoms on 2D-GaAs: a route to chiral magnetic 2D materials by design.

Using relativistic density-functional calculations, we examine the magneto-crystalline anisotropy and exchange properties of transition-metal atoms adsorbed on 2D-GaAs. We show that single Mn and Mo atom (Co and Os) strongly bind on 2D-GaAs, and induce local out-of-plane (in-plane) magnetic anisotropy. When a pair of TM atoms is adsorbed on 2D-GaAs in a close range from each other, magnetisation properties change (become tunable) with respect to concentrations and ordering of the adatoms. In all cases, we reveal presence of strong Dzyaloshinskii-Moriya interaction. These results indicate novel pathways towards two-dimensional chiral magnetic materials by design, tailored for desired applications in magneto-electronics.

Glucocorticoid-mediated control of the activation and clonal deletion of peripheral T cells in vivo.

Poly- and oligoclonal T cell stimuli like anti-CD3 epsilon monoclonal antibody or Staphylococcus aureus enterotoxin B (SEB), injected at doses that per se are not lethal, provoke acute death within less than 24 h, provided that endogenous glucocorticoids (GC) are depleted by adrenalectomy or by injection of saturating amounts of the GC receptor antagonist RU-38486 (mifepristone). Pharmacological doses of the GC agonist dexamethasone (DEX) alter the in vivo response of splenic V beta 8+ T cells to SEB, thus impeding the expansion of such cells and causing their rapid (3 d) clonal deletion. In contrast, coadministration of RU-38486 counteracts a SEB-induced early (12 h) reduction of V beta 8+CD4+ and V beta 8+CD8+ spleen cells. In vivo T cell stimulation by injection of bacterial superantigen induces a rapid (peak at 90-120 min) increase in corticosterone serum levels, suggesting that endogenous GC might control early T cell activation. Accordingly, kinetic studies revealed that RU-38486 has to be administered within 2 h after superantigen administration to exert its lethal effect. Similarly, exogenous GC must be injected during this critical phase (2 h) to rescue animals from acute death induced by coinjection of SEB and D-galactosamine (GalN). Adrenalectomy, injection of RU-38486 and priming with GalN per se provoke the programmed death of peripheral CD4+ and CD8+ T cells. Thus, three manipulations that sensitize mice for the lethal effect of T cell stimulation also exert a proapoptotic effect on peripheral T cells. In synthesis, endogenous and exogenous GC regulate T cell responses and determine the propensity of peripheral T cells to undergo apoptosis.

Two-dimensional hydrogenated buckled gallium arsenide: an ab initio study.

First-principles calculations have been carried out to investigate the stability, structural and electronic properties of two-dimensional (2D) hydrogenated GaAs with three possible geometries: chair, zigzag-line and boat configurations. The effect of van der Waals interactions on 2D H-GaAs systems has also been studied. These configurations were found to be energetic and dynamic stable, as well as having a semiconducting character. Although 2D GaAs adsorbed with H tends to form a zigzag-line configuration, the energy differences between chair, zigzag-line and boat are very small which implies the metastability of the system. Chair and boat configurations display a [Formula: see text]-[Formula: see text] direct bandgap nature, while pristine 2D-GaAs and zigzag-line are indirect semiconductors. The bandgap sizes of all configurations are also hydrogen dependent, and wider than that of pristine 2D-GaAs with both PBE and HSE functionals. Even though DFT-vdW interactions increase the adsorption energies and reduce the equilibrium distances of H-GaAs systems, it presents, qualitatively, the same physical results on the stability and electronic properties of our studied systems with PBE functional. According to our results, 2D buckled gallium arsenide is a good candidate to be synthesized by hydrogen surface passivation as its group III-V partners 2D buckled gallium nitride and boron nitride. The hydrogenation of 2D-GaAs tunes the bandgap of pristine 2D-GaAs, which makes it a potential candidate for optoelectronic applications in the blue and violet ranges of the visible electromagnetic spectrum.

Scattering from colloidal cubic silica shells: Part II, static structure factors and osmotic equation of state.

HYPOTHESIS: The shape of colloidal particles affects the structure of colloidal dispersions. The effect of the cube shape on the thermodynamics of colloidal cube dispersions has not yet been studied experimentally. Static light scattering measurements on colloidal cubic silica shells at finite concentrations allows us to measure the structure factor of colloidal cube fluids and to test theoretical predictions for the equation of state of hard convex superballs. EXPERIMENTS: Hollow silica nanocubes of varying concentrations in N,N,-dimethylformamide were studied with static light scattering. The structure factor was extracted from the scattering curves using experimental form factors. From this experimental structure factor, the specific density of the particles, and the osmotic compressibility were obtained. This osmotic compressibility was then compared to a theoretical equation of state of hard superballs. FINDINGS: The first experimental structure factors of a stable cube fluid are presented. The osmotic compressibility of the cube fluid can be described by the equation of state of a hard superball fluid, showing that silica cubes in N,N,-dimethylformamide with LiCl effectively interact as hard particles.

Tunable 2D-gallium arsenide and graphene bandgaps in a graphene/GaAs heterostructure: an ab initio study.

The bandgap behavior of 2D-GaAs and graphene have been investigated with van der Waals heterostructured into a yet unexplored graphene/GaAs bilayer, under both uniaxial stress along c axis and different planar strain distributions. The 2D-GaAs bandgap nature changes from [Formula: see text]-K indirect in isolated monolayer to [Formula: see text]-[Formula: see text] direct in graphene/GaAs bilayer. In the latter, graphene exhibits a bandgap of 5 meV. The uniaxial stress strongly affects the graphene electronic bandgap, while symmetric in-plane strain does not open the bandgap in graphene. Nevertheless, it induces remarkable changes on the GaAs bandgap-width around the Fermi level. However, when applying asymmetric in-plane strain to graphene/GaAs, the graphene sublattice symmetry is broken, and the graphene bandgap is open at the Fermi level to a maximum width of 814 meV. This value is much higher than that reported for just graphene under asymmetric strain. The [Formula: see text]-[Formula: see text] direct bandgap of GaAs remains unchanged in graphene/GaAs under different types of applied strain. The analyses of phonon dispersion and the elastic constants yield the dynamical and mechanical stability of the graphene/GaAs system, respectively. The calculated mechanical properties for bilayer heterostructure are better than those of their constituent monolayers. This finding, together with the tunable graphene bandgap not only by the strength but also by the direction of the strain, enhance the potential for strain engineering of ultrathin group-III-V electronic devices hybridized by graphene.

Vibrational properties of germanane and fluorinated germanene in the chair, boat, and zigzag-line configurations.

The electronic and vibrational properties of germanane and fluorinated germanene are studied within density functional theory (DFT) and density functional perturbation theory frameworks. Different structural configurations of germanane and fluorinated germanene are investigated. The energy difference between the different configurations are consistently smaller than the energy of thermal fluctuations for all the analyzed DFT functionals LDA, GGA, and hybrid functionals, which implies that, in principle, it is possible to find these different configurations in different regions of the sample as minority phases or local defects. We calculate the Raman and infrared spectra for these configurations by using ab initio calculations and compare it with available experimental spectra for germanane. Our results show the presence of minority phases compatible with the configurations analyzed in this work. As these low energy configurations are metastable the present work shows that the synthesis of these energy competing phases is feasible by selectively changing the synthesis conditions, which is an opportunity to expand in this way the availability of new two-dimensional compounds.

Changes in tuberculosis in human immunodeficiency virus infected patients in a Spanish tertiary hospital (1995-2013).

OBJECTIVE: Although the incidence of human immunodeficiency virus (HIV)-associated tuberculosis (TB) has decreased, changes in other characteristics of the disease are largely unknown. To describe the trends in TB in patients infected with HIV from 1995 to 2013. METHODS: We review all cases of TB in a tertiary hospital in Madrid, Spain. RESULTS: Among 1,284 patients diagnosed of TB, 298 (23%) were coinfected with HIV. The prevalence of HIV infection during the period of study has decreased from 40% to 14% (p for the trend < 0.001). Clinical presentation has also changed. Although pulmonary and extrapulmonary TB has remained unchanged, miliary presentation has significantly decreased (from 36% to 22%, p = 0.005). The 4-drug regimen was the preferable scheme, with higher implementation at the end of the study period (82% from 1995-1999 to 95% in 2010-2013, p = 0.43). Factors such as treatment failure (OR: 11.7; CI 95%: 3.12-44.1) and miliary form (OR: 2.8; CI 95%; 1.09-7.3) were independently associated with TB related mortality, while the longer duration of treatment was as a protective factor (OR 0.7; CI 95%: 0.6-0.8). CONCLUSIONS: HIV has decreased very significantly as a risk factor for the development of TB. Despite improvement in the treatment of both TB and HIV, and in overall mortality, deaths attributable to the disease in this population remain high mostly in miliary and relapsing forms.

Nivel de dependencia funcional de los adultos mayores de la comunidad de Tula de Allende / Level of functional dependence of older adults in the community of Tula de Allende

Introducción: El estado funcional se mide mediante la autonomía que tienen las personas para desarrollar las actividades de la vida diaria, cuando no se pueden realizar de manera autónoma es necesario un cuidador. Esta medida se sustenta en el modelo de adaptación de Sor Callista Roy, ya que se identifica el proceso de envejecimiento como el estímulo focal que produce una respuesta inmediata en el adulto mayor de acuerdo con el modo de interdependencia. Objetivo: Conocer el nivel de dependencia funcional de los adultos mayores de la comunidad de Tula de Allende, Hidalgo. Material y métodos: Estudio de aplicabilidad básica, cuantitativo, descriptivo y trasversal. Participaron 366 adultos mayores de Tula de Allende, y se les dio a conocer los términos de confidencialidad conforme a lo establecido en la Ley General de Salud y Declaración de Helsinki mediante el consentimiento informado. Se aplicó el cuestionario de Índice de Barthel (IB), para medir la dependencia funcional en las actividades instrumentales de la vida diaria. Resultados: Predomina el género femenino con el 52.7% representado por 193 participantes, la mayoría son casadas y amas de casa. De acuerdo con el IB la mayoría de los participantes tiene una dependencia leve, con una frecuencia de 206 y un porcentaje de 56.3%, y el cruce de variables arroja como resultado una relación significativa. Conclusión: Los adultos mayores de la comunidad de Tula de Allende presentan un nivel de dependencia funcional leve.

Introduction: Functional status assesses people's ability to carry out daily activities; when these cannot be performed autonomously, a caregiver is necessary. This measure is based on the Roy Adaptation Model, which identifies the aging process as the focal stimulus that generates an effect according to the interdependence mode. Objective: To evaluate the level of functional dependence of the elderly in the community of Tula de Allende, Hidalgo. Material and methods: Quantitative, descriptive, and cross-sectional study of basic applicability. 366 older adults from Tula de Allende participated and were informed about confidentiality terms in accordance with the General Health Law and the Declaration of Helsinki through informed consent. The Barthel Index (BI) questionnaire was applied to measure functional dependence on daily instrumental activities. Results: The female gender predominates with 52.7% represented by 193 participants, the majority are married housewives. According to the BI, most of the participants have a slight dependency, with a frequency of 206 and a percentage of 56.3%; the correlation of variables showed statistical significance. Conclusion: Older adults in the community of Tula de Allende present a mild functional dependence level.