Chronic lymphocytic leukaemia: the role of T cells in a B cell disease

Chronic lymphocytic leukaemia (CLL) has long been thought to be an immunosuppressive disease and abnormalities in T‐cell subset distribution and function have been observed in many studies. However, the role of T cells (if any) in disease progression remains unclear and has not been directly studied. This has changed with the advent of new therapies, such as chimeric antigen receptor‐T cells, which actively use retargeted patient‐derived T cells as “living drugs” for CLL. However complete responses are relatively low (~26%) and recent studies have suggested the differentiation status of patient T cells before therapy may influence efficacy. Non‐chemotherapeutic drugs, such as idelalisib and ibrutinib, also have an impact on T cell populations in CLL patients. This review will highlight what is known about T cells in CLL during disease progression and after treatment, and discuss the prospects of using T cells as predictive biomarkers for immune status and response to therapy

Encephalopathy and encephalitis during acute SARS-CoV-2 infection. Spanish Society of Neurology COVID-19 Registry

Objectives: Since the beginning of the COVID-19 pandemic, the Spanish Society of Neurology has run a registry of patients with neurological involvement for the purpose of informing clinical neurologists. Encephatopathy and encephalitis were among the most frequently reported complications. In this study, we analyse the characteristics of these complications. Patients and methods: We conducted a retrospective, descriptive, observational, multicentre study of patients with symptoms compatible with encephalitis or encephalopathy, entered in the Spanish Society of Neurology''s COVID-19 Registry from 17 March to 6 June 2020. Results: A total of 232 patients with neurological symptoms were registered, including 51 cases of encephalopathy or encephalitis (21.9%). None of these patients were healthcare professionals. The most frequent syndromes were mild or moderate confusion (33%) and severe encephalopathy or coma (9.8%). The mean time between onset of infection and onset of neurological symptoms was 8.02 days. Lumbar puncture was performed in 60.8% of patients, with positive PCR results for SARS-CoV-2 in only one case. Brain MRI studies were performed in 47% of patients, with alterations detected in 7.8% of these. EEG studies were performed in 41.3% of cases, detecting alterations in 61.9%. Conclusions: Encephalopathy and encephalitis are among the complications most frequently reported in the registry. More than one-third of patients presented mild or moderate confusional syndrome. The mean time from onset of infection to onset of neurological symptoms was 8 days (up to 24 hours earlier in women than in men). EEG was the most sensitive test in these patients, with very few cases presenting alterations in neuroimaging studies. All patients treated with boluses of corticosteroids or immunoglobulins progressed favourably. (C) 2021 Sociedad Espanola de Neurologia. Published by Elsevier Espana, S.L.U

RICORS2040 : The need for collaborative research in chronic kidney disease

Chronic kidney disease (CKD) is a silent and poorly known killer. The current concept of CKD is relatively young and uptake by the public, physicians and health authorities is not widespread. Physicians still confuse CKD with chronic kidney insufficiency or failure. For the wider public and health authorities, CKD evokes kidney replacement therapy (KRT). In Spain, the prevalence of KRT is 0.13%. Thus health authorities may consider CKD a non-issue: very few persons eventually need KRT and, for those in whom kidneys fail, the problem is 'solved' by dialysis or kidney transplantation. However, KRT is the tip of the iceberg in the burden of CKD. The main burden of CKD is accelerated ageing and premature death. The cut-off points for kidney function and kidney damage indexes that define CKD also mark an increased risk for all-cause premature death. CKD is the most prevalent risk factor for lethal coronavirus disease 2019 (COVID-19) and the factor that most increases the risk of death in COVID-19, after old age. Men and women undergoing KRT still have an annual mortality that is 10- to 100-fold higher than similar-age peers, and life expectancy is shortened by ~40 years for young persons on dialysis and by 15 years for young persons with a functioning kidney graft. CKD is expected to become the fifth greatest global cause of death by 2040 and the second greatest cause of death in Spain before the end of the century, a time when one in four Spaniards will have CKD. However, by 2022, CKD will become the only top-15 global predicted cause of death that is not supported by a dedicated well-funded Centres for Biomedical Research (CIBER) network structure in Spain. Realizing the underestimation of the CKD burden of disease by health authorities, the Decade of the Kidney initiative for 2020-2030 was launched by the American Association of Kidney Patients and the European Kidney Health Alliance. Leading Spanish kidney researchers grouped in the kidney collaborative research network Red de Investigación Renal have now applied for the Redes de Investigación Cooperativa Orientadas a Resultados en Salud (RICORS) call for collaborative research in Spain with the support of the Spanish Society of Nephrology, Federación Nacional de Asociaciones para la Lucha Contra las Enfermedades del Riñón and ONT: RICORS2040 aims to prevent the dire predictions for the global 2040 burden of CKD from becoming true

Co-limitation towards lower latitudes shapes global forest diversity gradients

The latitudinal diversity gradient (LDG) is one of the most recognized global patterns of species richness exhibited across a wide range of taxa. Numerous hypotheses have been proposed in the past two centuries to explain LDG, but rigorous tests of the drivers of LDGs have been limited by a lack of high-quality global species richness data. Here we produce a high-resolution (0.025° × 0.025°) map of local tree species richness using a global forest inventory database with individual tree information and local biophysical characteristics from ~1.3 million sample plots. We then quantify drivers of local tree species richness patterns across latitudes. Generally, annual mean temperature was a dominant predictor of tree species richness, which is most consistent with the metabolic theory of biodiversity (MTB). However, MTB underestimated LDG in the tropics, where high species richness was also moderated by topographic, soil and anthropogenic factors operating at local scales. Given that local landscape variables operate synergistically with bioclimatic factors in shaping the global LDG pattern, we suggest that MTB be extended to account for co-limitation by subordinate drivers

<i>Trypanosoma brucei</i>: TbRAB4 regulates membrane recycling and expression of surface proteins in procyclic forms

TbRAB4 is the Trypanosoma brucei orthologue of the small GTPase Rab4, which is implicated in the control of early endocytosis and recycling processes. TbRAB4 is expressed constitutively in the procyclic and bloodstream stages suggesting an important function throughout the trypanosome life-cycle. Previous work from our laboratory has shown TbRAB4 to be essential in the bloodstream form. Induction of double-stranded TbRAB4 RNA expression leads to a specific reduction in TbRAB4 protein levels and inhibition of growth in procyclic form T. brucei, with alterations in uptake and recycling as measured with the fluorophore FM4-64. Trypanosomes overexpressing GTP-locked TbRAB4QL mutants exhibit significant perturbations of endocytic and recycling pathways as well as disruption of surface expression of GPI-anchored proteins. Most significantly, both the endogenous GPI-anchored procyclins and an ectopically expressed GPI-anchored protein, the variant surface glycoprotein, are relocated from the surface to internal sites in TbRAB4 mutant cells. These data indicate that TbRAB4 is important in maintenance of normal surface expression of lipid-anchored proteins, and implicate recycling pathways as factors for modulation of surface protein expression in the procyclic trypanosome. The conservation of function of Rab4 throughout eukaryotic evolution demonstrated here indicates that the Rab4-mediated trafficking pathway is an extremely ancient component of the endocytic system

One to Two Days of Rest Is Recommended Before Returning to Sport After Intra-Articular Corticosteroid Injection in the High-Level Athlete

Return to sport following a corticosteroid injection is a complex decision. Multiple considerations should be taken into account, including steroid dose and formulation, involvement of the affected joint in the activity, and intensity of the activity. Research investigating the adverse effects of corticosteroid injections with early initiation of high-intensity activity is limited and has produced mixed results. Rest following injections has typically been recommended to minimize both chondrotoxic effects and systemic absorption. Based on the current research and extensive experience treating professional athletes, we recommend 1 to 2 days of rest of the affected joint or region with a progressive increase of activity following a corticosteroid injection with possible benefits including maximizing the beneficial effects of the injection and a reduced systemic effect. Level of Evidence: Level V, expert opinion