Role of allogeneic hematopoietic cell transplant for relapsed/refractory aggressive B-cell lymphomas in the CART era.

Anti-CD19 chimeric antigen receptor T cells (CART) has rapidly been adopted as the standard third-line therapy to treat aggressive B-cell lymphomas (ABCL) after failure of second-line therapy despite the lack of direct comparisons with allogeneic hematopoietic cell transplantation (alloHCT)-based strategies. Using the Grupo Español de Trasplante y Terapia Celular (GETH-TC) registry, we selected patients with the following characteristics: CART or alloHCT performed between 2016 and 2021; ≥18 years old; ABCL diagnosis; ≥2 lines of therapy; and either anti-CD19 CART or alloHCT as therapy at relapse. The analysis included a total of 316 (CART = 215, alloHCT = 101) patients. Median follow-up was 15 and 36 months for the CART and alloHCT cohorts, respectively. In the multivariate analysis, CART was confirmed to be similar to alloHCT for the primary study endpoint (progression-free survival) (hazard ratio [HR] 0.92, CI95%:0.56-1.51, p = 0.75). Furthermore, when the analysis was limited to only patients with chemo-sensitive diseases (complete and partial response) at infusion (CART = 26, alloHCT=93), no differences were reported (progression-free survival at month +18: 65% versus 55%, p = 0.59). However, CART had lower non-relapse mortality (HR 0.34, 95% CI: 0.13-0.85, p = 0.02). Given the lower toxicity and similar survival outcomes, these results suggest the use of CART before alloHCT.

Afecciones, manifestaciones y repercusiones neurológicas del COVID-19 / COVID-19 conditions, manifestations, and neurological repercussions

Resumen Inetroducción: El Síndrome Respiratorio Agudo Severo (SARS-CoV-2) es la entidad patológica responsable de la actual pandemia que no solo genera un cuadro respiratorio distintivo sino que también se ha asociado con múltiples mecanismos de invasión al sistema nervioso central (SNC). Objetivo: Determinar las afecciones, manifestaciones y repercusiones neurológicas que puede generar la infección por SARS-CoV-2. Métodos: Revisión de la literatura científica de pacientes con infección por SARS-CoV-2, en quienes se evaluó desarrollo de afecciones, manifestaciones y repercusiones neurológicas, desenlace seleccionado en los estudios, presencia de afecciones micro y macroscópicas del SNC y periférico (SNP). Resultados: Se estudiaron 40 artículos que analizaban la familia y estructura del SARS-CoV-2, mecanismos fisiopatológicos, manifestaciones clínicas neurológicas y las posibles repercusiones a nivel sistema nervioso central. Conclusiones: El SARS-CoV-2 es una entidad patológica que se asocia a distintos mecanismos de intervención neurológica, por medio de infección directa al SNC, secundario a un proceso parainfeccioso y postinfeccioso, relacionado con el síndrome de tormenta de citoquinas, daño endotelial, trastornos trombóticos, adicionalmente de secundario a hipoxia, hipoxemia y fallo multiorgánico.

Abstract Introduction: Severe Acute Respiratory Syndrome (SARS-CoV-2) is the pathological entity responsible for the current pandemic that not only generates a distinctive respiratory pattern but has also been associated with multiple mechanisms of invasion of the central nervous system (CNS). Objective: To determine the affections, manifestations and neurological repercussions that SARS-CoV-2 infection can generate. Methods: Review of the scientific literature of patients with SARS-CoV-2 infection, in whom the development of conditions, manifestations and neurological repercussions, selected outcome in the studies, presence of micro and macroscopic conditions of the CNS and peripheral (PNS) were evaluated. Results: 40 articles were included where the family and structure of SARS-CoV-2, pathophysiological mechanisms, neurological clinical manifestations, and possible repercussions at the central nervous system level were analyzed. Conclusions: SARS-CoV-2 is a pathological entity that is associated with different mechanisms of neurological intervention, through direct infection to the CNS, secondary to a parainfectious and postinfectious process, related to cytokine storm syndrome, endothelial damage, thrombotic disorders, in addition to secondary to hypoxia, hypoxemia and multiple organ failure.

Incidence, diagnosis, and outcome of immune-mediated thrombotic thrombocytopenic purpura: A nationwide survey by the Spanish registry of thrombotic thrombocytopenic purpura.

BACKGROUND: Immune-mediated thrombotic thrombocytopenic purpura (iTTP) is a rare disease characterized by the presence of anti-ADAMTS13 autoantibodies. Achieving accurate information on incidence and customary disease management is important to provide appropriate diagnostic and therapeutic resources. The aim of this study was to determine the incidence and outcomes of iTTP in Spain. STUDY DESIGN AND METHODS: A cross-sectional survey was carried out among Spanish hospitals, focused on iTTP patients ≥16 years old attended between 2015 and 2017, and those at follow-up before that interval. Incidence, prevalence, mortality, refractoriness, exacerbations, treatment complications, relapses, and sequelae were estimated. RESULTS: Forty-two hospitals covering roughly 20 million inhabitants answered the survey and reported 203 episodes (138 newly-diagnosed and 65 relapses), of which 193 (95.1%) were treated. Incidence was 2.67 (95% CI 1.90-3.45) patients per million inhabitants per year and prevalence 21.44 (95% CI% 19.10-23.73) patients per million inhabitants. At diagnosis, ADAMTS13 activity and anti-ADAMTS13 autoantibody were measured in 97% and 84.3% of reported episodes, respectively. Fifteen patients (7.4%) died as a direct consequence of iTTP, 6 of them before receiving any iTTP-specific treatment. Thirty-one (16.1%) of the 193 treated episodes were refractory to plasma exchange and corticosteroids, and 51 (26.4%) suffered at least one exacerbation. CONCLUSION: iTTP incidence and prevalence were somewhat higher than those documented in neighboring countries. Together with data on treatments and outcomes, this information will allow us to better estimate what is needed to improve diagnosis and prognosis of iTTP patients in Spain.

Addition of plerixafor to G-CSF in poor mobilizing healthy related donors overcame mobilization failure: An observational case series on behalf of the Grupo Español de Trasplante Hematopoyético (GETH).

Plerixafor (Mozobil, Sanofi) is approved for using in patients with lymphoma and multiple myeloma when steady-state mobilization strategies fail. Although off-label use of plerixafor in healthy related donors (HRD) is known, limited data are available and no recommendations exist to guide its use in this setting. With the aim of collecting data from HRDs who received plerixafor in our country, we designed an observational case series study within the Spanish Group of Hematopoietic Transplant and Cell Therapy (GETH). Plerixafor was administered subcutaneously to 30 HRDs at a median dose of 0.24 mg/Kg (interquartile range (IQR): 0.23-0.25) because mobilization failure after using mobilization with G-CSF (mobilization failure was defined as collection of <4.0 × 106 CD34+ cells/Kg recipient). All HRDs received G-CSF at a median dose of 11 µg/Kg/day (IQR: 10-12) for 4-5 days. Leukocytapheresis after G-CSF mobilization was performed in 23 (77 %) HRDs collecting a median of 1.6 × 106 CD34+ cells/Kg recipient weight (IQR: 0.9-2.5). Addition of plerixafor allowed the collection of a higher median number of CD34 cells (4.98 × 106 CD34+ cells/Kg recipient weight (IQR: 3.5-5.8)) when compared with the collection of CD34+ cells with G-CSF alone (p < 0.01). The final median total number of CD34+ cells collected was 6.1 × 106/Kg recipient weight (IQR: 4.8-7.3). Mild adverse events related with plerixafor administration were reported in 8 (27 %) donors. In conclusion, addition of plerixafor after G-CSF mobilization failure in HRDs allowed collecting higher number of CD34+ cells in comparison with steady-state mobilization.

Experiências de atendimento online a crianças e adolescentes em tempos de COVID-19 / Experiencias de terapia en línea con niños y adolescentes en tiempos de COVID-19 / Online therapy experiences for children and adolescents during the COVID-19 / Expériences d'assistance en ligne pour les enfants et les adolescents en temps du COVID-19

Este artigo propõe a discussão em torno dos atendimentos online realizados por estudantes de Psicologia de uma universidade pública, orientadas pela psicanálise, tendo em vista a pandemia COVID-19. Com o distanciamento físico imposto como medida sanitária para controle do coronavírus, foi necessário reinventar a prática com crianças e adolescentes desenvolvida em três contextos diferentes, a saber: estágio em um Centro de Atenção Psicossocial Infantojuvenil (CAPSi); extensão no projeto Atendimento Psicanalítico em Clínica Escola; e extensão no projeto Adolescência, Acolhimento Institucional e Clínica do Desamparo. Buscou-se abordar aspectos que sustentam o dispositivo analítico frente à mudança na modalidade dos atendimentos, visando sustentar uma reflexão teórica, ética e política

Este artículo propone un debate en torno a la atención psicológica en línea que prestan los estudiantes de psicología de una universidad pública, guiados por el psicoanálisis, en el contexto de la pandemia de COVID-19. Con el distanciamiento social impuesto como medida sanitaria para controlar el coronavirus, fue necesario reinventar la práctica con niños y adolescentes desarrollada en tres contextos diferentes, a saber: pasantía en un Centro de Atención Psicosocial Infantil y Juvenil (CAPSi); extensión universitaria en el proyecto "Asistencia Psicoanalítica en una escuela clínica"; y en el proyecto "Adolescencia, Acogida Institucional y Clínica del Desamparo". Se buscó abordar los aspectos que aseguran el dispositivo analítico ante el cambio en la modalidad de atención, buscando sustentar una reflexión teórica, ética y política

This article aims to discuss online consultations performed by Psychology students at a public university, guided by Psychoanalysis, in view of COVID-19 pandemic. Social distancing was imposed as a sanitary measure for the control of the coronavirus and this regulation compelled us to reinvent the psychological practices with children and adolescents. The practices are developed in three different contexts, namely: a traineeship at a Psychosocial Care Center for Children and Adolescents (CAPSi); an university extension project "Psychoanalytic practices at training clinic"; and the project "Adolescence, Institutional Care and Clinic of Helplessness". The article seeks to discuss aspects that maintain the analytical device in the face of changes in psychological care, in order to support a theoretical, ethical and political reflection

Cet article porte sur l'assistance en ligne proposée par des étudiants de Psychologie d'une université publique, guidée par la psychanalyse, en raison de la pandémie de la COVID-19. Avec la distanciation sociale imposée comme mesure sanitaire pour contrôler le coronavirus, il a fallu réinventer la pratique avec des enfants et des adolescents. Des pratiques sont développées en trois contextes différents, à savoir : un centre de soins psychosociaux pour enfants et adolescents (CAPSi); le projet d'extension universitaire "Consultations psychanalytiques dans la clinique publique"; et le projet "Adolescence, Accueil institutionnell et Clinique de la Détresse". Le but est d'aborder les aspects qui soutiennent le dispositif analytique face aux changements de type d'assistance, servant d'appui à une réflexion théorique, éthique et politique

Retrospective Multicenter Study of Extracorporeal Photopheresis in Steroid-Refractory Acute and Chronic Graft-versus-Host Disease.

Extracorporeal photopheresis (ECP) is an established treatment strategy in steroid-refractory graft-versus-host disease (GVHD). This study's main objective was to analyze the clinical response and impact of ECP therapy in steroid dose reduction. A retrospective observational series of 113 patients from 7 transplantation centers was analyzed. Sixty-five patients (58%) had acute GVHD (aGVHD), and 48 (42%) had chronic GVHD (cGVHD). All ECP procedures were performed with the off-line system. The median number of procedures until achievement of initial response was 3 for both patients with aGVHD and those with cGVHD. ECP was the second-line therapy in 48% of the aGVHD cases and in 50% of the cGVHD cases. 71% of the cases of aGVHD were grade III-IV, and 69% of the cases of cGVHD were severe. The overall response rate on day 28 was 53% (complete response [CR] rate, 45%) in the patients with aGVHD and 67% (CR, 23%) in those with cGVHD. Skin was the most frequently involved organ, with a response rate of 58% (CR, 49%) in the patients with aGVHD and 69% (CR 29%) in those with cGVHD. At the end of ECP treatment, 60% of patients treated for aGVHD who responded were able to stop steroid therapy, with a median dose reduction of 100%. Significant differences in overall survival were observed for patients responding to ECP with aGVHD (hazard ratio [HR], 4.3; P < .001) and with cGVHD (HR, 4.8; P = .003). Our data indicate that ECP is a valid therapeutic alternative in patients with steroid-refractory aGVHD and cGVHD, permitting significant steroid dosage reductions.

Leukemia risk in children exposed to benzene and PM10 from vehicular traffic: a case-control study in an Italian population.

Benzene, a recognized occupational leukemogen in adults, has been hypothesized to also increase the risk of childhood leukemia. We carried out a population-based case-control study in a northern Italy community involving 83 cases with acute childhood leukemia diagnosed in the years 1998-2009 and 332 matched controls. We assessed residential exposure to benzene and to particulate matter ≤10 µm (PM10) from motorized traffic using geocoded residences and detailed emission and dispersion modeling. Exposure to benzene, and to a lesser extent to PM10, appeared to be independently associated with an excess leukemia risk. When we stratified the study population by age and by leukemia subtype, the relative risk associated with benzene exposure was higher among children aged less than 5 years, and despite small numbers this relation appeared to be considerably stronger for acute myeloid leukemia than for acute lymphoblastic leukemia. Overall, these findings suggest that exposure to low levels of benzene released from motorized traffic may increase the risk of childhood leukemia, and suggest a possible independent effect of PM10, although unmeasured confounding due to other pollutants cannot be ruled out.

Cirurgia guiada associada à cirurgia minimamente invasiva- "flapless"

A satisfação do paciente no consultório odontológico é almejada através de procedimentos nenos traumáticos, com tempo cirúrgico reduzido, ocazionando melhor pós-oeratório e longevidade dos trabalhos realizados...

North African influences and potential bias in case-control association studies in the Spanish population.

BACKGROUND: Despite the limited genetic heterogeneity of Spanish populations, substantial evidences support that historical African influences have not affected them uniformly. Accounting for such population differences might be essential to reduce spurious results in association studies of genetic factors with disease. Using ancestry informative markers (AIMs), we aimed to measure the African influences in Spanish populations and to explore whether these might introduce statistical bias in population-based association studies. METHODOLOGY/PRINCIPAL FINDINGS: We genotyped 93 AIMs in Spanish (from the Canary Islands and the Iberian Peninsula) and Northwest Africans, and conducted population and individual-based clustering analyses along with reference data from the HapMap, HGDP-CEPH, and other sources. We found significant differences for the Northwest African influence among Spanish populations from as low as ≈ 5% in Spanish from the Iberian Peninsula to as much as ≈ 17% in Canary Islanders, whereas the sub-Saharan African influence was negligible. Strikingly, the Northwest African ancestry showed a wide inter-individual variation in Canary Islanders ranging from 0% to 96%, reflecting the violent way the Islands were conquered and colonized by the Spanish in the XV century. As a consequence, a comparison of allele frequencies between Spanish samples from the Iberian Peninsula and the Canary Islands evidenced an excess of markers with significant differences. However, the inflation of p-values for the differences was adequately controlled by correcting for genetic ancestry estimates derived from a reduced number of AIMs. CONCLUSIONS/SIGNIFICANCE: Although the African influences estimated might be biased due to marker ascertainment, these results confirm that Northwest African genetic footprints are recognizable nowadays in the Spanish populations, particularly in Canary Islanders, and that the uneven African influences existing in these populations might increase the risk for false positives in association studies. Adjusting for population stratification assessed with a few dozen AIMs would be sufficient to control this effect.

Renin expression in hematological malignancies and its role in the regulation of hematopoiesis.

It has been demonstrated that some myeloid blasts express renin, but normal bone marrow (BM) does not display this expression. The aim of the present work was to analyze the renin expression in different hematological malignancies and different myeloid cell lines. We investigated the expression of renin by RT-PCR in BM from patients with hematological malignancies (106 patients), in nine normal BM from healthy donors and in leukemic cell lines (K562, KU812, MEG-01, U-937 and HL60), as well in K562 cell line subjected to differentiation treatments. We have observed renin expression in cells from acute myeloid leukemia (AML), chronic myelogenous leukemia (CML) and acute lymphoblastic leukemia (ALL) cases. The highest frequency was observed in AML-non acute promyelocytic leukemia(APL) cases (47.2% of the cases). The disappearance of this expression was associated with the status of complete remission of AML. Renin is expressed in some myeloid human leukemia cell lines such as K562, KU812 and MEG-01. However, when K562 cells were treated with inducers of growth inhibition and/or differentiation, the expression did not disappear, indicating that renin expression is associated with a blastic phenotype rather than with cell proliferation. The obtained findings suggest that the renin expression could have a role on the disease development and could be used as an aberrant marker of leukemia.