Toxicities of Immunosuppressive Treatment of Autoimmune Neurologic Diseases

In parallel to our better understanding of the role of the immune system in neurologic diseases, there has been an increased availability in therapeutic options for autoimmune neurologic diseases such as multiple sclerosis, myasthenia gravis, polyneuropathies, central nervous system vasculitides and neurosarcoidosis. In many cases, the purported benefits of this class of therapy are anecdotal and not the result of good controlled clinical trials. Nonetheless, their potential efficacy is better known than their adverse event profile. A rationale therapeutic decision by the clinician will depend on a comprehensive understanding of the ratio between efficacy and toxicity. In this review, we outline the most commonly used immune suppressive medications in neurologic disease: cytotoxic chemotherapy, nucleoside analogues, calcineurin inhibitors, monoclonal antibodies and miscellaneous immune suppressants. A discussion of their mechanisms of action and related toxicity is highlighted, with the goal that the reader will be able to recognize the most commonly associated toxicities and identify strategies to prevent and manage problems that are expected to arise with their use

Análise da correção atmosférica de imagens Landsat em estudo multitemporal na região de Mata Atlântica, Estado do Rio de Janeiro.

Multitemporal, remotely sensed data applied to land use land cover dynamic studies require radiometric correction of images, in addition to geometric correction. This allow the analysis of temporal variation of targets without the influence of others factors such as the atmospheric effects. This study aims to apply the dark-object subtraction technique to correct atmospheric effects and to analyze the results on multitemporal images of rivers Macacu and Caceribu watersheds, in Rio de Janeiro state, in Atlantic Forest region. Images without clouds from sensors TM/Landsat-5 and ETM+/Landsat-7 were selected for analysis of land use land cover dynamic of two periods: 1997 to 2002 and 2002 to 2007. The results indicated that the correction method did not reduce the atmospheric effects in a satisfactory manner. These effects continued to influence in any significant way in the spectral response of the targets. The major differences between the levels of gray of the corrected images were among the images of different sensors, indicating likely influence of the response of the sensors on the final results. o objetivo do presente trabalho é analisar o efeito da correção atmosférica aplicando método de subtração de nível de ci nza em imagens multitemporais da região das bacias hidrográficas dos rios Macacu e Caceribu, no Estado do Rio de Janeiro, em região de Mata Atlântica

Methotrexate Encephalopathy: Two Cases in Adult Cancer Patients, Who Recovered with Pathophysiologically Based Therapy

Background/Objectives: Neurotoxicity is a serious and sometimes fatal adverse effect that can occur following methotrexate treatment. We describe two adult patients with hematological malignancies with methotrexate encephalopathy who recovered with dextromethorphan therapy. Results: Case 1 : A 24-year-old male with acute lymphoblastic leukemia developed the acute onset of bilateral facial weakness and slurred speech after his first treatment with high-dose intravenous methotrexate. The clinical scenario and a head magnetic resonance imaging supported a diagnosis of methotrexate encephalopathy. Treatment with dextromethorphan was coincident with recovery. Case 2 : A 65-year-old female with recurrent diffuse large B-cell lymphoma was treated with high- dose intravenous methotrexate. Two weeks after a cycle, she developed hypoactive delirium, marked lethargy, ocular ataxia, and a right-sided facial weakness. Within 2 days of starting dextromethorphan, there was improvement with clinical recovery. Conclusions: These two cases suggest that N -methyl d -aspartate receptor activation by homocysteine may play an important role in the pathogenesis of methotrexate neurotoxicity

The Advent of CAR T-Cell Therapy for Lymphoproliferative Neoplasms: Integrating Research Into Clinical Practice

Research on CAR T cells has achieved enormous progress in recent years. After the impressive results obtained in relapsed and refractory B-cell acute lymphoblastic leukemia and aggressive B-cell lymphomas, two constructs, tisagenlecleucel and axicabtagene ciloleucel, were approved by FDA. The role of CAR T cells in the treatment of B-cell disorders, however, is rapidly evolving. Ongoing clinical trials aim at comparing CAR T cells with standard treatment options and at evaluating their efficacy earlier in the disease course. The use of CAR T cells is still limited by the risk of relevant toxicities, most commonly cytokine release syndrome and neurotoxicity, whose management has nonetheless significantly improved. Some patients do not respond or relapse after treatment, either because of poor CAR T-cell expansion, lack of anti-tumor effects or after the loss of the target antigen on tumor cells. Investigators are trying to overcome these hurdles in many ways: by testing constructs which target different and/or multiple antigens or by improving CAR T-cell structure with additional functions and synergistic molecules. Alternative cell sources including allogeneic products (off-the-shelf CAR T cells), NK cells, and T cells obtained from induced pluripotent stem cells are also considered. Several trials are exploring the curative potential of CAR T cells in other malignancies, and recent data on multiple myeloma and chronic lymphocytic leukemia are encouraging. Given the likely expansion of CAR T-cell indications and their wider availability over time, more and more highly specialized clinical centers, with dedicated clinical units, will be required. Overall, the costs of these cell therapies will also play a role in the sustainability of many health care systems. This review will focus on the major clinical trials of CAR T cells in B-cell malignancies, including those leading to the first FDA approvals, and on the new settings in which these constructs are being tested. Besides, the most promising approaches to improve CAR T-cell efficacy and early data on alternative cell sources will be reviewed. Finally, we will discuss the challenges and the opportunities that are emerging with the advent of CAR T cells into clinical routine

Dinâmica de uso e cobertura da terra nas bacias hidrográficas de Guapi-Macacu e Caceribu - RJ.

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Beyond property: Rural politics and land-use change in the Colombian sugarcane landscape

Analysing the sugarcane landscape in the flat valley of the Cauca River (Colombia) reveals that agricultural industrialization in the region required the concentration of land use by regional industrialists and the corresponding exclusion of landowners and poor peasants from territorial decision-making processes. The analytical lens used in this article, based on the use and control over land and land-based natural commons, allows for the characterization of three periods in a non-linear process of articulation and dispute between poor peasant and capitalist agents in the expansion of the sugarcane monoculture during the 20th century. The different constellations of social agents, governmental nexus, and capital enclosures have enacted through mechanisms that, beyond concentrating land property, have managed to deprive rural ethnic communities from their cultural and environmental heritage, traditional economies, and possible futures.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/151270/1/joac12332_am.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/151270/2/joac12332.pd

Impact of cancer and chemotherapy on autonomic nervous system function and cardiovascular reactivity in young adults with cancer: a case-controlled feasibility study

Background Preliminary evidence suggests cancer- and chemotherapy-related autonomic nervous system (ANS) dysfunction may contribute to the increased cardiovascular (CV) morbidity- and mortality-risks in cancer survivors. However, the reliability of these findings may have been jeopardized by inconsistent participant screening and assessment methods. Therefore, good laboratory practices must be established before the presence and nature of cancer-related autonomic dysfunction can be characterized. The purpose of this study was to assess the feasibility of conducting concurrent ANS and cardiovascular evaluations in young adult cancer patients, according to the following criteria: i) identifying methodological pitfalls and proposing good laboratory practice criteria for ANS testing in cancer, and ii) providing initial physiologic evidence of autonomic perturbations in cancer patients using the composite autonomic scoring scale (CASS). Methods Thirteen patients (mixed diagnoses) were assessed immediately before and after 4 cycles of chemotherapy. Their results were compared to 12 sex- and age-matched controls. ANS function was assessed using standardized tests of resting CV (tilt-table, respiratory sinus arrhythmia and Valsalva maneuver) and sudomotor (quantitative sudomotor axon reflex test) reactivity. Cardiovascular reactivity during exercise was assessed using a modified Astrand-Ryhming cycle ergometer protocol. Our feasibility criteria addressed: i) recruitment potential, ii) retention rates, iii) pre-chemotherapy assessment potential, iv) test performance/tolerability, and v) identification and minimizing the influence of potentially confounding medication. T-tests and repeated measures ANOVAs were used to assess between- and within-group differences at baseline and follow-up. Results The overall success rate in achieving our feasibility criteria was 98.4 %. According to the CASS, there was evidence of ANS impairment at baseline in 30.8 % of patients, which persisted in 18.2 % of patients at follow-up, compared to 0 % of controls at baseline or follow-up. Conclusions Results from our feasibility assessment suggest that the investigation of ANS function in young adult cancer patients undergoing chemotherapy is possible. To the best of our knowledge, this is the first study to report CASS-based evidence of ANS impairment and sudomotor dysfunction in any cancer population. Moreover, we provide evidence of cancer- and chemotherapy-related parasympathetic dysfunction – as a possible contributor to the pathogenesis of CV disease in cancer survivors