Brentuximab vedotin in the treatment of cutaneous T-cell lymphomas: Data from the Spanish Primary Cutaneous Lymphoma Registry

[Background] Brentuximab vedotin (BV) has been approved for CD30-expressing cutaneous T-cell lymphoma (CTCL) after at least one previous systemic treatment. However, real clinical practice is still limited.[Objectives] To evaluate the response and tolerance of BV in a cohort of patients with CTCL.[Methods] We analysed CTCL patients treated with BV from the Spanish Primary Cutaneous Lymphoma Registry (RELCP).[Results] Sixty-seven patients were included. There were 26 females and the mean age at diagnosis was 59 years. Forty-eight were mycosis fungoides (MF), 7 Sézary syndrome (SS) and 12 CD30+ lymphoproliferative disorders (CD30 LPD). Mean follow-up was 18 months. Thirty patients (45%) showed at least 10% of CD30+ cells among the total lymphocytic infiltrate. The median number of BV infusions received was 7. The overall response rate (ORR) was 67% (63% in MF, 71% in SS and 84% in CD30 LPD). Ten of 14 patients with folliculotropic MF (FMF) achieved complete or partial response (ORR 71%). The median time to response was 2.8 months. During follow-up, 36 cases (54%) experienced cutaneous relapse or progression. The median progression free survival (PFS) was 10.3 months. The most frequent adverse event was peripheral neuropathy (PN) (57%), in most patients (85%), grades 1 or 2.[Conclusions] These results confirm the efficacy and safety of BV in patients with advanced-stage MF, and CD30 LPD. In addition, patients with FMF and SS also showed a favourable response. Our data suggest that BV retreatment is effective in a proportion of cases.The Spanish Primary Cutaneous Lymphoma Registry (RELCP) is promoted by the Fundación Piel Sana Academia Española de Dermatología y Venereología, which received an unrestricted grant support from Kyowa Kirin.Peer reviewe

Spatiotemporal Characteristics of the Largest HIV-1 CRF02_AG Outbreak in Spain: Evidence for Onward Transmissions

Background and Aim: The circulating recombinant form 02_AG (CRF02_AG) is the predominant clade among the human immunodeficiency virus type-1 (HIV-1) non-Bs with a prevalence of 5.97% (95% Confidence Interval-CI: 5.41–6.57%) across Spain. Our aim was to estimate the levels of regional clustering for CRF02_AG and the spatiotemporal characteristics of the largest CRF02_AG subepidemic in Spain.Methods: We studied 396 CRF02_AG sequences obtained from HIV-1 diagnosed patients during 2000–2014 from 10 autonomous communities of Spain. Phylogenetic analysis was performed on the 391 CRF02_AG sequences along with all globally sampled CRF02_AG sequences (N = 3,302) as references. Phylodynamic and phylogeographic analysis was performed to the largest CRF02_AG monophyletic cluster by a Bayesian method in BEAST v1.8.0 and by reconstructing ancestral states using the criterion of parsimony in Mesquite v3.4, respectively.Results: The HIV-1 CRF02_AG prevalence differed across Spanish autonomous communities we sampled from (p < 0.001). Phylogenetic analysis revealed that 52.7% of the CRF02_AG sequences formed 56 monophyletic clusters, with a range of 2–79 sequences. The CRF02_AG regional dispersal differed across Spain (p = 0.003), as suggested by monophyletic clustering. For the largest monophyletic cluster (subepidemic) (N = 79), 49.4% of the clustered sequences originated from Madrid, while most sequences (51.9%) had been obtained from men having sex with men (MSM). Molecular clock analysis suggested that the origin (tMRCA) of the CRF02_AG subepidemic was in 2002 (median estimate; 95% Highest Posterior Density-HPD interval: 1999–2004). Additionally, we found significant clustering within the CRF02_AG subepidemic according to the ethnic origin.Conclusion: CRF02_AG has been introduced as a result of multiple introductions in Spain, following regional dispersal in several cases. We showed that CRF02_AG transmissions were mostly due to regional dispersal in Spain. The hot-spot for the largest CRF02_AG regional subepidemic in Spain was in Madrid associated with MSM transmission risk group. The existence of subepidemics suggest that several spillovers occurred from Madrid to other areas. CRF02_AG sequences from Hispanics were clustered in a separate subclade suggesting no linkage between the local and Hispanic subepidemics

All-cause mortality in the cohorts of the Spanish AIDS Research Network (RIS) compared with the general population: 1997Ł2010

Abstract Background: Combination antiretroviral therapy (cART) has produced significant changes in mortality of HIVinfected persons. Our objective was to estimate mortality rates, standardized mortality ratios and excess mortality rates of cohorts of the AIDS Research Network (RIS) (CoRIS-MD and CoRIS) compared to the general population. Methods: We analysed data of CoRIS-MD and CoRIS cohorts from 1997 to 2010. We calculated: (i) all-cause mortality rates, (ii) standardized mortality ratio (SMR) and (iii) excess mortality rates for both cohort for 100 personyears (py) of follow-up, comparing all-cause mortality with that of the general population of similar age and gender. Results: Between 1997 and 2010, 8,214 HIV positive subjects were included, 2,453 (29.9%) in CoRIS-MD and 5,761 (70.1%) in CoRIS and 294 deaths were registered. All-cause mortality rate was 1.02 (95% CI 0.91-1.15) per 100 py, SMR was 6.8 (95% CI 5.9-7.9) and excess mortality rate was 0.8 (95% CI 0.7-0.9) per 100 py. Mortality was higher in patients with AIDS, hepatitis C virus (HCV) co-infection, and those from CoRIS-MD cohort (1997. Conclusion: Mortality among HIV-positive persons remains higher than that of the general population of similar age and sex, with significant differences depending on the history of AIDS or HCV coinfection

Introduction to the binder jet technology in additive manufacturing of metals

La fabricació additiva de metall ha experimentat un creixement molt ràpid gràcies als desenvolupaments tecnològics i a les inversions en recerca. Entre els diferents mètodes de fabricació additiva hi està la tècnica d'injecció d'aglomerant, la qual es basa en la fabricació d'una peça capa per capa mitjançant la deposició selectiva d'aglutinant fluid sobre un llit de pols metàl·lic. Després del procés d'impressió, les peces obtingudes s'han de sotmetre a un curat i a una densificació posterior. En aquest treball es recopila informació necessària per poder comprendre aquesta tècnica, a més de ser una guia sobre la selecció de la matèria primera i l'optimització dels paràmetres del procés. Es revisen les característiques de la pols, les propietats de l'aglutinant i els paràmetres del procés d'impressió que més influeixen en les propietats de les peces finals. Per tant, el que es tracta és que aquest treball sigui com una avantsala a futurs projectes en col·laboració amb HP on es procedeixi a estudiar la pols metàl·lic i la seva influència en la selecció d'alguns paràmetres de de el procés.La fabricación aditiva de metal ha experimentado un crecimiento muy rápido gracias a los desarrollos tecnológicos y a las inversiones en investigación. Entre los diferentes métodos de fabricación aditiva existe la técnica de inyección de aglomerante o binder jetting en inglés, el cual se basa en la fabricación de una pieza capa por capa mediante la deposición selectiva de aglutinante fluido sobre un lecho de polvo metálico. Tras el proceso de impresión, las piezas obtenidas deben de someterse a un curado y a una densificación posterior. En este trabajo se recopila información necesaria para poder comprender dicha técnica, además de ser una guía sobre la selección de la materia prima y la optimización de los parámetros del proceso. Se revisan las características del polvo, las propiedades del aglutinante y los parámetros del proceso de impresión que más influyen en las propiedades de las piezas finales. Por lo tanto, lo que se trata es de que este trabajo sea como una antesala a futuros proyectos en colaboración con HP donde se proceda a estudiar el polvo metálico y su influencia en la selección de algunos parámetros de del proceso.Metal additive manufacturing has seen very rapid growth in recent years thanks to technological developments and research investments. Among the different additive manufacturing methods, there is the technique of Binder Jetting, which is based on the manufacture of piece layer by layer by the selective deposition of fluid binder on a bed of metallic powder. After the printing process, the pieces obtained must undergo curing and subsequent densification. This work collects the information necessary to understand this technique, in addition to being a guide on the selection of the raw material and the optimization of the process parameters. The characteristics of the powder, the properties of the binder, and the parameters of the printing process that most influence the properties of the final pieces are reviewed. Therefore, what this is about is that this work is a prelude to future projects in collaboration with HP where the metallic powder is studied and its influence on the selection of some process parameters

Estudio técnico-económico de una línea de fabricación industrial para la obtención de plastificantes naturales de ácido poliláctico (PLA) a partir de aceites vegetales

[ES] El objetivo central del proyecto es el desarrollo de una línea de fabricación industrial de plastificantes naturales para ácido poliláctico (PLA) a partir de aceites vegetales modificados químicamente, concretamente, mediante procesos de maleinización. El proyecto contempla el estudio y optimización del proceso de extracción de los aceites, evaluación de rendimientos, así como la definición de las condiciones de maleinización del aceite seleccionado, con el fin de transferir estos parámetros en el proceso de escalado industrial. Este escalado contemplará el predimensionamiento de la línea de fabricación en términos de equipos, instalaciones, etc., junto con un estudio sobre la viabilidad económica de la línea.[EN] Design of a plasticizer production plant for the PLA from the maleinization process of castor oil. In this project, the design, assembly and study of the economic viability of a plant for the production of a plasticizer from vegetable oils through the maleinization of it is carried out. The control of the quality of the plasticizer is also carried out by analytical techniques. From the simulations, the reaction speed is studied in order to then dimension the process. On the other hand, the properties that will be granted by plasticiser to the new polymer will be studied to ensure that it is a good plasticizer.[CA] En aquest projecte es realitza el disseny, el muntatge i l'estudi de la viabilitat econòmica d'una planta de producció d'un plastificant a partir d'olis vegetals per mitjà de la maleinizació d'este. Paral·lelament es defineixen les tècniques d'anàlisi per a controlar la qualitat d'este plastificant. A partir de les simulacions s'estudia la velocitat de reacció para a continuació poder dimensionar el procés. D'altra banda, s'estudiaran les propietats que atorgarà al polímer per a assegurar que el nou material és un bon plastificant.Blanes Martínez, MDM. (2017). Estudio técnico-económico de una línea de fabricación industrial para la obtención de plastificantes naturales de ácido poliláctico (PLA) a partir de aceites vegetales. http://hdl.handle.net/10251/97868TFG

Bioresorbable Chitosan-Based Bone Regeneration Scaffold Using Various Bioceramics and the Alteration of Photoinitiator Concentration in an Extended UV Photocrosslinking Reaction

Bone tissue engineering (BTE) is an ongoing field of research based on clinical needs to treat delayed and non-union long bone fractures. An ideal tissue engineering scaffold should have a biodegradability property matching the rate of new bone turnover, be non-toxic, have good mechanical properties, and mimic the natural extracellular matrix to induce bone regeneration. In this study, biodegradable chitosan (CS) scaffolds were prepared with combinations of bioactive ceramics, namely hydroxyapatite (HAp), tricalcium phosphate-α (TCP- α), and fluorapatite (FAp), with a fixed concentration of benzophenone photoinitiator (50 µL of 0.1% (w/v)) and crosslinked using a UV curing system. The efficacy of the one-step crosslinking reaction was assessed using swelling and compression testing, SEM and FTIR analysis, and biodegradation studies in simulated body fluid. Results indicate that the scaffolds had comparable mechanical properties, which were: 13.69 ± 1.06 (CS/HAp), 12.82 ± 4.10 (CS/TCP-α), 13.87 ± 2.9 (CS/HAp/TCP-α), and 15.55 ± 0.56 (CS/FAp). Consequently, various benzophenone concentrations were added to CS/HAp formulations to determine their effect on the degradation rate. Based on the mechanical properties and degradation profile of CS/HAp, it was found that 5 µL of 0.1% (w/v) benzophenone resulted in the highest degradation rate at eight weeks (54.48% degraded), while maintaining compressive strength between (4.04 ± 1.49 to 10.17 ± 4.78 MPa) during degradation testing. These results indicate that incorporating bioceramics with a suitable photoinitiator concentration can tailor the biodegradability and load-bearing capacity of the scaffolds

COVID-19 in hospitalized HIV-positive and HIV-negative patients : A matched study

CatedresObjectives: We compared the characteristics and clinical outcomes of hospitalized individuals with COVID-19 with [people with HIV (PWH)] and without (non-PWH) HIV co-infection in Spain during the first wave of the pandemic. Methods: This was a retrospective matched cohort study. People with HIV were identified by reviewing clinical records and laboratory registries of 10 922 patients in active-follow-up within the Spanish HIV Research Network (CoRIS) up to 30 June 2020. Each hospitalized PWH was matched with five non-PWH of the same age and sex randomly selected from COVID-19@Spain, a multicentre cohort of 4035 patients hospitalized with confirmed COVID-19. The main outcome was all-cause in-hospital mortality. Results: Forty-five PWH with PCR-confirmed COVID-19 were identified in CoRIS, 21 of whom were hospitalized. A total of 105 age/sex-matched controls were selected from the COVID-19@Spain cohort. The median age in both groups was 53 (Q1-Q3, 46-56) years, and 90.5% were men. In PWH, 19.1% were injecting drug users, 95.2% were on antiretroviral therapy, 94.4% had HIV-RNA < 50 copies/mL, and the median (Q1-Q3) CD4 count was 595 (349-798) cells/μL. No statistically significant differences were found between PWH and non-PWH in number of comorbidities, presenting signs and symptoms, laboratory parameters, radiology findings and severity scores on admission. Corticosteroids were administered to 33.3% and 27.4% of PWH and non-PWH, respectively (P = 0.580). Deaths during admission were documented in two (9.5%) PWH and 12 (11.4%) non-PWH (P = 0.800). Conclusions: Our findings suggest that well-controlled HIV infection does not modify the clinical presentation or worsen clinical outcomes of COVID-19 hospitalization

Prediction of long-term outcomes of HIV-infected patients developing non-AIDS events using a multistate approach

Outcomes of people living with HIV (PLWH) developing non-AIDS events (NAEs) remain poorly defined. We aimed to classify NAEs according to severity, and to describe clinical outcomes and prognostic factors after NAE occurrence using data from CoRIS, a large Spanish HIV cohort from 2004 to 2013. Prospective multicenter cohort study. Using a multistate approach we estimated 3 transition probabilities: from alive and NAE-free to alive and NAE-experienced ("NAE development"); from alive and NAE-experienced to death ("Death after NAE"); and from alive and NAE-free to death ("Death without NAE"). We analyzed the effect of different covariates, including demographic, immunologic and virologic data, on death or NAE development, based on estimates of hazard ratios (HR). We focused on the transition "Death after NAE". 8,789 PLWH were followed-up until death, cohort censoring or loss to follow-up. 792 first incident NAEs occurred in 9.01% PLWH (incidence rate 28.76; 95% confidence interval [CI], 26.80-30.84, per 1000 patient-years). 112 (14.14%) NAE-experienced PLWH and 240 (2.73%) NAE-free PLWH died. Adjusted HR for the transition "Death after NAE" was 12.1 (95%CI, 4.90-29.89). There was a graded increase in the adjusted HRs for mortality according to NAE severity category: HR (95%CI), 4.02 (2.45-6.57) for intermediate-severity; and 9.85 (5.45-17.81) for serious NAEs compared to low-severity NAEs. Male sex (HR 2.04; 95% CI, 1.11-3.84), ag

Discovering HIV related information by means of association rules and machine learning

Acquired immunodeficiency syndrome (AIDS) is still one of the main health problems worldwide. It is therefore essential to keep making progress in improving the prognosis and quality of life of affected patients. One way to advance along this pathway is to uncover connections between other disorders associated with HIV/AIDS-so that they can be anticipated and possibly mitigated. We propose to achieve this by using Association Rules (ARs). They allow us to represent the dependencies between a number of diseases and other specific diseases. However, classical techniques systematically generate every AR meeting some minimal conditions on data frequency, hence generating a vast amount of uninteresting ARs, which need to be filtered out. The lack of manually annotated ARs has favored unsupervised filtering, even though they produce limited results. In this paper, we propose a semi-supervised system, able to identify relevant ARs among HIV-related diseases with a minimal amount of annotated training data. Our system has been able to extract a good number of relationships between HIV-related diseases that have been previously detected in the literature but are scattered and are often little known. Furthermore, a number of plausible new relationships have shown up which deserve further investigation by qualified medical experts