The role of red blood cell exchange for severe imported malaria in the artesunate era: a retrospective cohort study in a referral centre

BACKGROUND: Intravenous artesunate has replaced quinine as the first-line therapy for severe imported malaria, given its anti-malarial superiority shown in clinical trials conducted in endemic countries. Evidence for red blood cell (RBC) exchange in patients with severe malaria treated with artesunate is lacking. This retrospective cohort study describes the experience at Hospital Clinic of Barcelona with the use of artesunate for severe malaria and the joint use of RBC exchange in selected cases. METHODS: Patients treated for severe malaria at Hospital Clinic of Barcelona between August 2013 and January 2015 were included in this retrospective study. Severe malaria was defined according to WHO criteria. Data were extracted from electronic hospital records. A log-linear mixed model approach was used to estimate parasite clearance times. RESULTS: Within the study period, 42 patients were diagnosed of malaria at this centre, of which 38 had Plasmodium falciparum (90.5 %). Sixteen patients (42 %) had severe malaria cases and were treated with intravenous artesunate. Four patients underwent RBC exchange within a period of 15 h after the first dose of artesunate (range 9-21 h). The procedure lasted a median of 2 h (IQR 1.8-2 h), using a median of 12 (IQR 11-14) units of packed RBCs to replace a median of 3794 ml (IQR 2977-4343). The technique was well-tolerated without haemodynamic complications. There were no deaths. The regression model showed an estimated time to 95 % decay of 21.6 h (95 % CI 17.3-28.8). When assessing effect modification by RBC exchange, there was no difference in the parasite elimination rate (p = 0.286). DISCUSSION AND CONCLUSION: In this study RBC exchange failed to show benefits in terms of parasite clearance probably due to the small number of patients analysed. The evidence for exchange transfusion remains limited

Front microrheology of the non-Newtonian behavior of blood: scaling theory of erythrocyte aggregation by aging

We introduce a new framework to study the non-Newtonian behaviour of fluids at the microscale based on the analysis of front advancement. We apply this methodology to study the non-linear rheology of blood in microchannels. We carry out experiments in which the non-linear viscosity of blood samples is quantified at different haematocrits and ages. Under these conditions, blood exhibits a power-law dependence on the shear rate. In order to analyse our experimental data, we put forward a scaling theory which allows us to define an adhesion scaling number. This theory yields a scaling behaviour of the viscosity expressed as a function of the adhesion capillary number. By applying this scaling theory to samples of different ages, we are able to quantify how the characteristic adhesion energy varies as time progresses. This connection between microscopic and mesoscopic properties allows us to estimate quantitatively the change in the cell-cell adhesion energies as the sample age

Capillary filling at the microscale: control of fluid front using geometry

We propose an experimental and theoretical framework for the study of capillary filling at the micro-scale. Our methodology enables us to control the fluid flow regime so that we can characterise properties of Newtonian fluids such as their viscosity. In particular, we study a viscous, non-inertial, non-Washburn regime in which the position of the fluid front increases linearly with time for the whole duration of the experiment. The operating shear-rate range of our apparatus extends over nearly two orders of magnitude. Further, we analyse the advancement of a fluid front within a microcapillary in a system of two immiscible Newtonian liquids. We observe a non-Washburn regime in which the front can accelerate or decelerate depending on the viscosity contrast between the two liquids. We then propose a theoretical model which enables us to study and explain both non-Washburn regimes. Furthermore, our theoretical model allows us to put forward ways to control the emergence of these regimes by means of geometrical parameters of the experimental set-up. Our methodology allows us to design and calibrate a micro-viscosimetre which works at constant pressure

T cells isolated from G-CSF-treated multiple myeloma patients are suitable for the generation of BCMA-directed CAR-T cells

Autologous cell immunotherapy using B cell maturation antigen (BCMA)-targeted chimeric antigen receptor (CAR)-T cells is an effective novel treatment for multiple myeloma (MM). This therapy has only been used for relapsed and refractory patients, at which stage the endogenous T cells used to produce the CAR-T cells are affected by the immunosuppressive nature of advanced MM and/or side effects of previous therapies. An alternative pool of fitter T cells is found in leukocytoapheresis products that are routinely collected to obtain hematopoietic progenitor cells for autologous stem cell transplantation (ASCT) early in the treatment of MM. However, to mobilize the progenitor cells, patients are dosed with granulocyte colony-stimulating factor (G-CSF), which is reported to adversely affect T cell proliferation, function, and differentiation. Here, we aimed to first establish whether G-CSF treatment negatively influences T cell phenotype and to ascertain whether previous exposure of T cells to G-CSF is deleterious for anti-BCMA CAR-T cells. We observed that G-CSF had a minimal impact on T cell phenotype when added in vitro or administered to patients. Moreover, we found that CAR-T cell fitness and anti-tumor activity were unaffected when generated from G-CSF-exposed T cells. Overall, we showed that ASCT apheresis products are a suitable source of T cells for anti-BCMA CAR-T cell manufacture

Rituximab, plasma exchange and immunoglobulins: an ineffective treatment for chronic active antibody-mediated rejection

BACKGROUND: Chronic active antibody-mediated rejection (c-aABMR) is an important cause of allograft failure and graft loss in long-term kidney transplants. METHODS: To determine the efficacy and safety of combined therapy with rituximab, plasma exchange (PE) and intravenous immunoglobulins (IVIG), a cohort of patients with transplant glomerulopathy (TG) that met criteria of active cABMR, according to BANFF'17 classification, was identified. RESULTS: We identified 62 patients with active c-aABMR and TG (cg ≥ 1). Twenty-three patients were treated with the combination therapy and, 39 patients did not receive treatment and were considered the control group. There were no significant differences in the graft survival between the two groups. The number of graft losses at 12 and 24 months and the decline of eGFR were not different and independent of the treatment. A decrease of eGFR≥13 ml/min between 6 months before and c-aABMR diagnosis, was an independent risk factor for graft loss at 24 months (OR = 5; P = 0.01). Infections that required hospitalization during the first year after c-aABMR diagnosis were significantly more frequent in treated patients (OR = 4.22; P = 0.013), with a ratio infection/patient-year of 0.65 and 0.20 respectively. CONCLUSIONS: Treatment with rituximab, PE, and IVIG in kidney transplants with c-aABMR did not improve graft survival and was associated with a significant increase in severe infectious complications

Fomentar el raonament crític i analític en el treball individual i grupal en l’alumnat de Psicologia

Donada la pluralitat d’opcions teòriques, metodològiques i d’intervenció en l’àrea psicosocial, aquest àmbit requereix de professionals amb competències d’anàlisi, reflexió crítica i treball en equip. En els actuals estudis de grau de Psicologia, la primera d’aquestes competències està present en 4 assignatures obligatòries de l’àmbit de la psicologia social i, la segona, en 2. Malgrat tot, en la pràctica docent, ambdues es retroalimenten, ja que el raonament analític i crític es nodreix del diàleg en el treball en equip i a la inversa. A partir d’aquí, l’objectiu del present projecte ha sigut, a través de les diferents assignatures obligatòries, desenvolupar una seqüència coordinada d’activitats formatives per millorar l’assoliment d’aquelles competències i posar en pràctica uns sistemes d’avaluació de les mateixes. A l’hora de redactar el projecte es preveia introduir unes practiques docents que de manera seqüenciada l’alumnat donés mostres de les competències assolides en termes de raonament crític i treball en grup. Els resultats aconseguits responen a los objectius plantejats tot i que d’acord amb les noves practiques i eines docents s’han d’anar any darrera any adaptant a les noves realitats.Vicerectorat de Política Docent i PMI

Development of a novel anti-CD19 chimeric antigen receptor: A paradigm for an affordable CAR T cell production at academic institutions

Genetically modifying autologous T cells to express an anti-CD19 chimeric antigen receptor (CAR) has shown impressive response rates for the treatment of CD19+ B cell malignancies in several clinical trials (CTs). Making this treatment available to our patients prompted us to develop a novel CART19 based on our own anti-CD19 antibody (A3B1), followed by CD8 hinge and transmembrane region, 4-1BB- and CD3z-signaling domains. We show that A3B1 CAR T cells are highly cytotoxic and specific against CD19+ cells in vitro, inducing secretion of pro-inflammatory cytokines and CAR T cell proliferation. In vivo, A3B1 CAR T cells are able to fully control disease progression in an NOD.Cg-Prkdcscid Il2rdtm1Wjl/SzJ (NSG) xenograph B-ALL mouse model. Based on the pre-clinical data, we conclude that our CART19 is clearly functional against CD19+ cells, to a level similar to other CAR19s currently being used in the clinic. Concurrently, we describe the implementation of our CAR T cell production system, using lentiviral vector and CliniMACS Prodigy, within a medium-sized academic institution. The results of the validation phase show our system is robust and reproducible, while maintaining a low cost that is affordable for academic institutions. Our model can serve as a paradigm for similar institutions, and it may help to make CAR T cell treatment available to all patients

Factors associated with the clinical outcome of patients with relapsed/refractory CD19+acute lymphoblastic leukemia treated with ARI-0001 CART19-cell therapy

The prognosis of patients with relapsed/refractory (R/R) acute lymphoblastic leukemia (ALL) remains poor, particularly for those relapsing after allogeneic hema-topoietic cell transplantation (alloHCT). Novel agents such as inotuzumab ozogamicin or blinatumomab achieve increased response rates, but these are generally transient unless followed by alloHCT. Chimeric antigen receptors (CAR) targeting CD19 have shown promising results in R/R ALL, and one of these products (tisagenlecleucel) has been approved for the treatment of patients with R/R ALL up to 25 years of age

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

XXII Setmana Internacional de Cinema Fomatiu. L’Educació Lliure i el Cinema Formatiu

XXII Setmana Internacional de Cinema Fomatiu: L’Educació Lliure i el Cinema Formatiu. 21 al 25 de novembre de 2016. Sala d'actes. Palau de les heures. Campus Mundet, Universitat de Barcelona.Fa 22 anys vàrem iniciar, arrel de la celebració del centenari del naixement del cinema, una activitat que encara avui mantenim: la SETMANA DE CINEMA FORMATIU. Una activitat per a aprofundir en una estratègia didàctica a partir del model ORA, dissenyat per un col·lectiu de professorat pertanyent al grup GIAD, concretament Saturnino de la Torre, Maria de Borja, Núria Rajadell i Maria Dolors Millan. Després d‟haver superat ja dues dècades seguim oferint aquest punt de trobada entre professorat i estudiants de diferents ensenyaments, amb la finalitat de debatre i reflexionar al voltant d‟una temàtica concreta, i, depenent de la temàtica seleccionada, i eixamplant la col·laboració amb altres institucions i professionals que treballen de manera específica amb la temàtica seleccionada. El Seminari de Cinema Formatiu, depenent del GIAD (Grup d‟Investigació i Assessorament Didàctic) de la Facultat d‟Educació de la Universitat de Barcelona, promou aquesta activitat però és un seminari de treball i de recerca obert a totes aquelles persones que estiguin interessades en el cinema, i puntualment a aquelles persones que estan interessades per la temàtica específica que es tracta al llarg de la Setmana. Alguns estudiants s‟han implicat i han passat a formar part del Seminari que l‟organitza. Aquest és l‟èxit i la raó d‟aquesta activitat, la implicació i la participació, el diàleg i l‟expressió de totes les persones que participen. Aquest any, arrel de l‟interessant debat que existeix en la nostra societat sobre la importància, necessitat i eficiència de l‟actual Sistema Educatiu, i amb la incorporació d‟entitats que es troben més enllà de l‟Administració i que han creat col·lectius per a aprofundir i visibilitzar la innovació educativa a les aules,hem considerat que podria ser interessant conèixer experiències més aviat trencadores del sistema escolar en què ens trobem immersos. Considerem interessant conèixer i reflexionar al voltant de propostes innovadores en el marc de l‟educació i la formació en un escenari complex, obert i global, com és en el que ens trobem immersos en aquests moments. Aquesta setmana comptem amb la col·laboració d‟un equip de professionals de diferents universitats i de diferents escoles catalanes que ens aportaran el seu coneixement des d‟un escenari privilegiat del nostre petit país com és Catalunya. Comptem, a més, amb una sèrie de pel·lícules que es visionaran i debatran en algunes de les classes, i amb una conferenciant que ha estat investigant en el marc de l‟educació lliure a Itàlia i a Catalunya, la Dra. Aurora Bosna