Factores biológicos y eficacia clínica de la fotoféresis extracorpórea en el tratamiento de la enfermedad injerto contra receptor refractaria

La enfermedad injerto contra receptor aguda y crónica (EICR aguda, EICR crónica), que se produce en algunos pacientes después del trasplante hematopoyético alogénico (TPH), es una complicación que confiere una gran morbi-mortalidad. El tratamiento estándar se realiza con corticoesteroides (CT) a altas dosis, pero sólo responden un 35% de los pacientes. En los pacientes que no responden, la segunda línea de tratamiento no está bien definida y en los últimos años la Fotoféresis Extracorpórea (FEC), un tipo de terapia celular con efecto inmunomodulador, ha demostrado ser un tratamiento eficaz y seguro en esta patología en pacientes adultos y pediátricos sin efecto inmunosupresor. Las guías internacionales actuales sobre el tratamiento de la EICR recomiendan su utilización con altos grados de evidencia sobre todo en la afectación cutánea. A pesar de los grandes avances realizados en esta terapia, continuamos sin conocer múltiples aspectos relacionados con factores biológicos y clínicos, como son el mecanismo exacto de acción, la dosis de celularidad eficaz y el esquema terapéutico óptimo. A finales del año 2009 iniciamos esta terapia a los pacientes con EICR aguda y crónica refractarios o dependientes del tratamiento con CT. El principal objetivo en este trabajo fue analizar la celularidad, en términos de células mononucleares (CMN) y de subpoblaciones linfocitarias (SPL), de los productos infundidos y su correlación con los valores de celularidad pre-aféresis de los pacientes. Adicionalmente se valoró el efecto de la FEC en la reconstitución inmune y la respuesta clínica en los pacientes estudiados..

Synthetic RGB photometry of bright stars: definition of the standard photometric system and UCM library of spectrophotometric spectra

Although the use of RGB photometry has exploded in the last decades due to the advent of high-quality and inexpensive digital cameras equipped with Bayer-like color filter systems, there is surprisingly no catalogue of bright stars that can be used for calibration purposes. Since due to their excessive brightness, accurate enough spectrophotometric measurements of bright stars typically cannot be performed with modern large telescopes, we have employed historical 13-color medium-narrow-band photometric data, gathered with quite reliable photomultipliers, to fit the spectrum of 1346 bright stars using stellar atmosphere models. This not only constitutes a useful compilation of bright spectrophotometric standards well spread in the celestial sphere, the UCM library of spectrophotometric spectra, but allows the generation of a catalogue of reference RGB magnitudes, with typical random uncertainties $\sim 0.01$ mag. For that purpose, we have defined a new set of spectral sensitivity curves, computed as the median of 28 sets of empirical sensitivity curves from the literature, that can be used to establish a standard RGB photometric system. Conversions between RGB magnitudes computed with any of these sets of empirical RGB curves and those determined with the new standard photometric system are provided. Even though particular RGB measurements from single cameras are not expected to provide extremely accurate photometric data, the repeatability and multiplicity of observations will allow access to a large amount of exploitable data in many astronomical fields, such as the detailed monitoring of light pollution and its impact on the night sky brightness, or the study of meteors, solar system bodies, variable stars, and transient objects. In addition, the RGB magnitudes presented here make the sky an accessible and free laboratory for the calibration of the cameras themselves.Comment: 19 pages, 18 figures, 7 tables. Accepted for publication in MNRA

The Free and Cued Selective Reminding Test in Parkinson's Disease Mild Cognitive Impairment : Discriminative Accuracy and Neural Correlates

Altres ajuts: This work was partially supported by grants from La Marató TV3 (20142910, 2014/U/477); FIS (PI14/02058, PI15/00962); CIBERNED.Introduction: Memory alterations are common in Parkinson's disease (PD) patients but the mechanisms involved in these deficits remain poorly understood. The study aims to explore the profile of episodic memory deficits in non-demented early PD patients. Methods: We obtained neurological, cognitive and behavioral data from 114 PD patients and 41 healthy controls (HC). PD participants were grouped as normal cognition (PD-NC) and mild cognitive impairment (PD-MCI) according to the Level II criteria of the Movement Disorders Society Task Force (MDS-TF). We evaluate the performance amongst groups on an episodic memory task using the Free and Cued Selective Reminding Test (FCSRT). Additionally, gray matter volume (GMV) voxel based morphometry, and mean diffusivity (MD) analyses were conducted in a subset of patients to explore the structural brain correlates of FCSRT performance. Results: Performance on all subscores of the FCSRT was significantly worse in PD-MCI than in PD-NC and HC. Delayed total recall (DTR) subscore was the best at differentiating PD-NC from PD-MCI. Using crosstabulation, DTR allowed identification of PD-MCI patients with an accuracy of 80%. Delayed free and cued recall was associated with decreased GMV and increased MD in multiple fronto-temporal and parietal areas. Conclusion: Encoding and retrieval deficits are a main characteristic of PD-MCI and are associated with structural damage in temporal, parietal and prefrontal areas

Prevalence and prognosis of anxiety, insomnia, and type D personality in patients with myocardial infarction: A Spanish cohort

Background: It has been suggested that patients with myocardial infarction and non-obstructive coronary arteries (MINOCA) have more psycho-emotional disorders than patients with obstructive coronary artery disease (MICAD). The aim of this study is to compare the prevalence of anxiety, insomnia, and type D personality between MINOCA and MICAD and their impact on prognosis. Methods: Patients with myocardial infarction undergoing coronary angiography were prospectively enrolled. Psychological questionnaires were completed by each patient during admission. Results: Among a total of 533 patients, 56 had MINOCA and 477 had MICAD. There were no differences in the prevalence of anxiety and insomnia between both groups: trait anxiety median value (M) MINOCA = 18 (11–34) vs. MICAD M = 19 (12–27), p = 0.8; state anxiety MINOCA M = 19 (11–29) vs. MICAD M = 19 (12.2–26), p = 0.6; and insomnia MINOCA M = 7 (3–11) vs. MICAD M = 7 (3–12), p = 0.95. More MINOCA patients had type D personality (45.0% vs. 28.5%, p = 0.03). At 3-year follow-up, there were no differences in mortality between MINOCA and MICAD (hazard ratio [HR] 0.78, 95% confidence interval [CI] 0.28–2.17) in major adverse cerebral or cardiovascular events (MACCE) (HR 0.71, 95% CI 0.38–1.31). Scores of trait anxiety and negative affectivity were significantly associated with MACCE (HR 1.65, 95% CI [1.05–2.57]; HR 1.75, 95% CI [1.11–2.77], respectively). High insomnia levels were associated with greater mortality (HR 2.72, 95% CI [1.12–6.61]). Conclusions: Anxiety and insomnia levels were similar between patients with MINOCA and those with MICAD, whilst the prevalence of type D personality was higher in the MINOCA than in the MICAD group. Higher scores in trait anxiety, insomnia, and negative affectivity were related to a worse prognosis at 3-year follow-up

Real-world effectiveness of caplacizumab vs the standard of care in immune thrombotic thrombocytopenic purpura

Immune thrombotic thrombocytopenic purpura (iTTP) is a thrombotic microangiopathy caused by anti-ADAMTS13 antibodies. Caplacizumab is approved for adults with an acute episode of iTTP in conjunction with plasma exchange (PEX) and immunosuppression. The objective of this study was to analyze and compare the safety and efficacy of caplacizumab vs the standard of care and assess the effect of the concomitant use of rituximab. A retrospective study from the Spanish TTP Registry of patients treated with caplacizumab vs those who did not receive it was conducted. A total of 155 patients with iTTP (77 caplacizumab, 78 no caplacizumab) were included. Patients initially treated with caplacizumab had fewer exacerbations (4.5% vs 20.5%; P < .05) and less refractoriness (4.5% vs 14.1%; P < .05) than those who were not treated. Time to clinical response was shorter when caplacizumab was used as initial treatment vs caplacizumab used after refractoriness or exacerbation. The multivariate analysis showed that its use in the first 3 days after PEX was associated with a lower number of PEX (odds ratio, 7.5; CI, 2.3-12.7; P < .05) and days of hospitalization (odds ratio, 11.2; CI, 5.6-16.9; P < .001) compared with standard therapy. There was no difference in time to clinical remission in patients treated with caplacizumab compared with the use of rituximab. No severe adverse event was described in the caplacizumab group. In summary, caplacizumab reduced exacerbations and refractoriness compared with standard of care regimens. When administered within the first 3 days after PEX, it also provided a faster clinical response, reducing hospitalization time and the need for PEX

Effectiveness of Following Mediterranean Diet Recommendations in the Real World in the Incidence of Gestational Diabetes Mellitus (GDM) and Adverse Maternal-Foetal Outcomes: A Prospective, Universal, Interventional Study with a Single Group. The St Carlos Study

We reported that a Mediterranean Diet (MedDiet), supplemented with extra-virgin olive oil (EVOO) and pistachios, reduces GDM incidence and several other adverse outcomes. In order to assess its translational effects in the real world we evaluated the effect of MedDiet from 1st gestational visit in GDM rate compared with control (CG) and intervention (IG) groups from the previously referred trial. As secondary objective we also compared adverse perinatal outcomes between normoglycemic and diabetic women. This trial is a prospective, clinic-based, interventional study with a single group. 1066 eligible normoglycaemic women before 12 gestational weeks were assessed. 932 women (32.4 ± 5.2 years old, pre-gestational BMI 22.5 ± 3.5 kg/m2) received a motivational lifestyle interview with emphasis on daily consumption of EVOO and nuts, were followed-up and analysed. Binary regression analyses were used to examine the risk for each pregnancy outcome, pregnancy-induced hypertension, preeclampsia, gestational weight gain (GWG), caesarean-section, perineal trauma, preterm delivery, small (SGA) and large for gestational age (LGA), and Neonatal Intensive Care Unit admissions. GDM was diagnosed in 13.9%. This rate was significantly lower than the CG: RR 0.81 (0.73–0.93), p < 0.001 and no different from the IG: RR 0.96 (0.85–1.07), p = 0.468. GWG was lower in diabetic women (10.88 ± 6.46 vs. 12.30 ± 5.42 Kg; p = 0.013). Excessive weight gain (EWG) was also lower in GDM [RR 0.91 (0.86–0.96); p < 0.001] without a significant increase of insufficient weight gain. LGA were also lower (1 (0.8%) vs. 31 (3.9%); p < 0.05)), and SGA were similar (5 (3.8%) vs. 30 (3.7%)). LGA were associated to EWG (RR 1.61 (1.35–1.91), p < 0.001). Differences in other maternal-foetal outcomes were not found. In conclusions an early MedDiet nutritional intervention reduces GDM incidence and maternal-foetal adverse outcomes and should be universally applied as 1st line therapy. GDM might not be consider as a high risk pregnancy any longer

Famílies botàniques de plantes medicinals

Facultat de Farmàcia, Universitat de Barcelona. Ensenyament: Grau de Farmàcia, Assignatura: Botànica Farmacèutica, Curs: 2013-2014, Coordinadors: Joan Simon, Cèsar Blanché i Maria Bosch.Els materials que aquí es presenten són els recull de 175 treballs d’una família botànica d’interès medicinal realitzats de manera individual. Els treballs han estat realitzat per la totalitat dels estudiants dels grups M-2 i M-3 de l’assignatura Botànica Farmacèutica durant els mesos d’abril i maig del curs 2013-14. Tots els treballs s’han dut a terme a través de la plataforma de GoogleDocs i han estat tutoritzats pel professor de l’assignatura i revisats i finalment co-avaluats entre els propis estudiants. L’objectiu principal de l’activitat ha estat fomentar l’aprenentatge autònom i col·laboratiu en Botànica farmacèutica

ADAMTS13 recovery in acute thrombotic thrombocytopenic purpura after caplacizumab therapy

Caplacizumab prevents the interaction between von Willebrand factor and platelets and is used to treat immune thrombotic thrombocytopenic purpura (iTTP). Its administration has been associated with a delay in ADAMTS13 activity restoration after plasma exchange (PEX) suspension. We analyzed the outcomes of 113 iTTP episodes, 75 of which were treated with caplacizumab, in 108 patients from the Spanish Registry of Thrombotic Thrombocytopenic Purpura. Caplacizumab shortened the time to platelet count normalization and reduced PEX requirement, exacerbations, and relapses. There was no difference in the time to achieve ADAMTS13 activity ≥20% after PEX end between caplacizumab-treated and nontreated episodes (median [interquartile range], 14.5 [7.7-27.2] vs 13.0 [8.0-29.0] days, P = .653). However, considering the 36 episodes in which caplacizumab was started ≤3 days after iTTP diagnosis, the time for ADAMTS13 restoration from PEX end was higher than in those episodes in which caplacizumab was started >3 days after iTTP diagnosis (20.0 [12.0-43.0] vs 11.0 [3.5-20.0] days, P = .003) or than in non-caplacizumab-treated episodes (P = .033). This finding could be related to a significantly shorter duration of PEX in early caplacizumab-treated episodes than in late caplacizumab-treated episodes (5.5 [4.0-9.0] vs 15.0 [11.0-21.5] days, P < .001) or non-caplacizumab-treated episodes (11.0 [6.0-26.0] days, P < .001). There were no differences in time to ADAMTS-13 restoration from PEX start (28.0 [17.2-47.5], 27.0 [19.0-37.5] and 29.5 [15.2-45.0] days in early caplacizumab-treated, late caplacizumab-treated and non-caplacizumab-treated episodes). Early administered caplacizumab does not prevent the requirement for immunosuppression but has beneficial effects by shortening PEX requirement without major safety concerns.Peer reviewe

Effectiveness of an intervention for improving drug prescription in primary care patients with multimorbidity and polypharmacy:Study protocol of a cluster randomized clinical trial (Multi-PAP project)

This study was funded by the Fondo de Investigaciones Sanitarias ISCIII (Grant Numbers PI15/00276, PI15/00572, PI15/00996), REDISSEC (Project Numbers RD12/0001/0012, RD16/0001/0005), and the European Regional Development Fund ("A way to build Europe").Background: Multimorbidity is associated with negative effects both on people's health and on healthcare systems. A key problem linked to multimorbidity is polypharmacy, which in turn is associated with increased risk of partly preventable adverse effects, including mortality. The Ariadne principles describe a model of care based on a thorough assessment of diseases, treatments (and potential interactions), clinical status, context and preferences of patients with multimorbidity, with the aim of prioritizing and sharing realistic treatment goals that guide an individualized management. The aim of this study is to evaluate the effectiveness of a complex intervention that implements the Ariadne principles in a population of young-old patients with multimorbidity and polypharmacy. The intervention seeks to improve the appropriateness of prescribing in primary care (PC), as measured by the medication appropriateness index (MAI) score at 6 and 12months, as compared with usual care. Methods/Design: Design:pragmatic cluster randomized clinical trial. Unit of randomization: family physician (FP). Unit of analysis: patient. Scope: PC health centres in three autonomous communities: Aragon, Madrid, and Andalusia (Spain). Population: patients aged 65-74years with multimorbidity (≥3 chronic diseases) and polypharmacy (≥5 drugs prescribed in ≥3months). Sample size: n=400 (200 per study arm). Intervention: complex intervention based on the implementation of the Ariadne principles with two components: (1) FP training and (2) FP-patient interview. Outcomes: MAI score, health services use, quality of life (Euroqol 5D-5L), pharmacotherapy and adherence to treatment (Morisky-Green, Haynes-Sackett), and clinical and socio-demographic variables. Statistical analysis: primary outcome is the difference in MAI score between T0 and T1 and corresponding 95% confidence interval. Adjustment for confounding factors will be performed by multilevel analysis. All analyses will be carried out in accordance with the intention-to-treat principle. Discussion: It is essential to provide evidence concerning interventions on PC patients with polypharmacy and multimorbidity, conducted in the context of routine clinical practice, and involving young-old patients with significant potential for preventing negative health outcomes. Trial registration: Clinicaltrials.gov, NCT02866799Publisher PDFPeer reviewe

Immune thrombotic thrombocytopenic purpura in older patients: Results from the Spanish TTP Registry (REPTT)

Immune thrombotic thrombocytopenic purpura (iTTP) is an ultra-rare disease that seldom occurs in the elderly. Few reports have studied the clinical course of iTTP in older patients. In this study, we have analysed the clinical characteristics at presentation and response to therapy in a series of 44 patients with iTTP ≥60 years at diagnosis from the Spanish TTP Registry and compared them with 209 patients with <60 years at diagnosis from the same Registry. Similar symptoms and laboratory results were described in both groups, except for a higher incidence of renal dysfunction among older patients (23% vs. 43.1%; p = 0.008). Front-line treatment in patients ≥60 years was like that administered in younger patients. Also, no evidence of a difference in clinical response and overall survival was seen in both groups. Of note, 14 and 25 patients ≥60 years received treatment with caplacizumab and rituximab, respectively, showing a favourable safety and efficacy profile, like that observed in patients <60 years.Peer reviewe