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Intraventricular hemorrhage is a common cause of morbidity and mortality in premature infants. The rupture of the germinal zone into the ventricles entails loss of neural stem cells and disturbs the normal cytoarchitecture of the region, compromising late neurogliogenesis. Here we demonstrate that neural stem cells can be easily and robustly isolated from the hemorrhagic cerebrospinal fluid obtained during therapeutic neuroendoscopic lavage in preterm infants with severe intraventricular hemorrhage. Our analyses demonstrate that these neural stem cells, although similar to human fetal cell lines, display distinctive hallmarks related to their regional and developmental origin in the germinal zone of the ventral forebrain, the ganglionic eminences that give rise to interneurons and oligodendrocytes. These cells can be expanded, cryopreserved, and differentiated in vitro and in vivo in the brain of nude mice and show no sign of tumoral transformation 6 months after transplantation. This novel class of neural stem cells poses no ethical concerns, as the fluid is usually discarded, and could be useful for the development of an autologous therapy for preterm infants, aiming to restore late neurogliogenesis and attenuate neurocognitive deficits. Furthermore, these cells represent a valuable tool for the study of the final stages of human brain development and germinal zone biology., Germinal zone neural stem cells (Gz‐NSC) are isolated from the hemorrhagic cerebrospinal fluid of preterm infants with severe intraventricular hemorrhage. These cells express ventral and posterior forebrain markers, can be differentiated and do not cause tumors. Gz‐NSC represent a valuable tool for the development of new cell therapies and the study of human Gz biology.

Purpose: To estimate the incidence rate (IR) and identify risk factors associated to inflammatory relapse after immunosuppressive drug (ISD) discontinuation in noninfectious uveitis patients. Methods: Multicenter longitudinal retrospective study, including patients from four uveitis clinics followed-up until December 2018. Hazard ratios for different variables were estimated using multivariable Cox models. Results: 32 patients (34 episodes of ISD discontinuation) were analyzed (median and maximum follow-up time: 2.4 and 19.2 years, respectively). Fourteen patients presented at least one relapse: anterior (8 patients), intermediate (5) and posterior (8). IR (95% confidence interval) of the first relapse was 14.3 (8.6–23.8) episodes per 100 patient-years (median survival time: 4.8 years). Early use of ISDs, panuveitis, and higher oral corticosteroid dosage at discontinuation were associated with higher hazards of relapse in multivariable analysis. Conclusions: Relapse is a frequent and early event after ISD discontinuation. Identifying relapse risk factors could support the physician’s decision regarding ISD discontinuation. Instituto de Salud Carlos III (ISCIII), Ministerio de Sanidad, Consumo y Bienestar Social (Contrato de investigación Miguel Servet: CPII17 / 00014 a LRR). 3.728 JCR (2021) Q2, 23/62 Ophthalmology 1,232 SJR (2021) Q1, 21/128 Ophthalmology No data IDR 2021 UEM

Objective Torque teno virus (TTV) is a highly prevalent non-pathogenic anellovirus whose plasma levels may be a biomarker of immunosuppression. The aim of this study was to assess whether specific immune-targeting with different biologic drugs may differentially modulate TTV viremia in arthritis patients. Methods TTV DNA load was quantified by PCR in a cross-sectional sample of 79 patients with chronic arthritis on biologic therapy (abatacept, infliximab, rituximab or tocilizumab), 31 patients treated with conventional DMARDs (methotrexate and/or leflunomide), and 54 healthy individuals. Longitudinal changes in TTV load were analysed in a second group of 59 patients at baseline and 4-months after biologic therapy. Correlations between clinical or biological characteristics of recruited patients and TTV viremia were also analysed. Results In the cross-sectional study, TTV load was significantly higher in patients who received abatacept, infliximab or tocilizumab compared to healthy individuals. Patients treated with rituximab or conventional DMARDs showed TTV loads similar to healthy controls. In the longitudinal study, an increase in the TTV load was observed after anti-TNF, tocilizumab, abatacept and rituximab, but not after secukinumab therapy. Correlations between TTV load and clinical variables such as disease duration, concomitant glucocorticoid or DMARDs therapy, lymphocytes or previous infections were not found. A non-significant trend towards higher TTV load was observed in therapy responders. Conclusion Patients with chronic arthritis on biologic but not on conventional DMARD or anti-IL17 therapy have increased TTV viremia. This observation provides a basis to prospectively explore the potential value of TTV load as a potential pharmacodynamic biomarker.

Resumen Objetivo Analisis comparativo del coste del tratamiento del linfedema de miembro superior secundario a cancer de mama, aplicando un modelo tradicional versus un modelo de vigilancia prospectiva. Cuantificar el ahorro derivado del abordaje prospectivo poscirugia. Pacientes y metodos Estudio retrospectivo de costes asociados al tratamiento del linfedema en el Hospital Ramon y Cajal y centros concertados. Se valoran 1.400 pacientes en consulta durante el ano 2014; de ellos, 212 precisaron terapia fisica compleja o de mantenimiento. Las variables analizadas son los costes directos, los costes indirectos y el ahorro estimado. Resultados El coste anual por paciente del tratamiento tradicional en el linfedema, a base de terapia fisica compleja en estadios, avanzados es 2.500 euros aproximadamente. En el modelo prospectivo todos los pacientes acuden a la Escuela de Linfedema y son evaluados posquirurgicamente. No suelen requerir terapia descongestiva, ni vendajes continuados y permite usar mangas prefabricadas menos costosas. Se evitan consultas y costes indirectos. Se incluye el coste del cribado y de la intervencion en estadios iniciales. El coste anual es aproximadamente el 25% de la cantidad estimada en el enfoque tradicional, unos 700 euros aproximadamente. Conclusiones La vigilancia prospectiva en el linfedema puede reducir la necesidad de rehabilitacion intensiva y es coste-efectiva. Supone un ahorro potencial del 75% del coste asociado al modelo tradicional vigente.

The difficulty in diagnosis and the spectrum of clinical manifestations that can determine the choice of treatment for primary antiphospholipid syndrome (APS) has fostered the development of recommendations by the Spanish Society of Rheumatology (SER), based on the best possible evidence. These recommendations can serve as a reference for rheumatologists and other specialists involved in the management of APS.A panel of four rheumatologists, a gynaecologist and a haematologist with expertise in APS was created, previously selected by the SER through an open call or based on professional merits. The stages of the work were: identification of the key areas for drafting the document, analysis and synthesis of the scientific evidence (using the Scottish Intercollegiate Guidelines Network [SIGN] levels of evidence) and formulation of recommendations based on this evidence and formal assessment or reasoned judgement techniques (consensus techniques).46 recommendations were drawn up, addressing five main areas: diagnosis and evaluation, measurement of primary thromboprophylaxis, treatment for APS or secondary thromboprophylaxis, treatment for obstetric APS and special situations. These recommendations also include the role of novel oral anticoagulants, the problem of recurrences or the key risk factors identified in these subjects. This document reflects the first 21, referring to the areas of: diagnosis, evaluation and treatment of primary APS. The document provides a table of recommendations and treatment algorithms.An update of the SER recommendations on APS is presented. This document corresponds to partI, related to diagnosis, evaluation and treatment. These recommendations are considered tools for decision-making for clinicians, taking into consideration both the decision of the physician experienced in APS and the patient. A partII has also been prepared, which addresses aspects related to obstetric SAF and special situations.

Objectives Issue recommendations on practical aspects of the monitoring of levels of biological drugs that may be useful for rheumatologists. Methods We conducted a systematic review of studies in which drug and anti-drug antibody levels were determined in patients with rheumatoid arthritis (RA) or spondyloarthritis (SpA) to study whether they could predict different outcomes. In light of the results of the review, a group of experts discussed under what circumstances testing biological drug levels and their antibodies could be useful. The discussion resulted in a series of clinical questions that were answered with the scientific evidence collected, and in algorithms that facilitate decision making. Results It was established that the determination of drug levels can be especially useful in two clinical situations, on treatment failure (primary or secondary) and on sustained remission. It is also reviewed which laboratory technique and timing for sample drawing are the most suitable for the measurement. Recommendations are issued on the interpretation of drug levels and on factors to be taken into account (for example, body mass index and disease modifying drugs). Conclusions Evidence-based algorithms and guidelines have been established to test drug levels and anti-drug antibodies in patients with RA and SpA, which can help clinical decision making.