Epidemiological surveillance of trachoma in a school in an urban area in Southeastern Brazil

INTRODUCTION: Epidemiological surveillance activities undertaken after the detection of an active trachoma case in the APAE-SP are described. MATERIAL AND METHOD: A total of 1,009 pupils, employees and household contacts had an eye examination. Treatment control was carried out at the institution 4 times at 45 day-intervals. RESULTS: The overall prevalence was of 5.9%, 5.1% being of follicular trachoma (TF), 0.3% of intense trachoma (TF/TI) and 0.5% of cicatricial trachoma (TS). At the first control exercise 45.5% of the trachoma cases had no signs of the disease and 40.0% underwent treatment. At the last control exercise 20% were found to have been cured with no vestigial scars. Non-attendance was of 38.2%. The distribution of secondary cases showed great dispersion, suggesting dissemination throughout Greater S. Paulo . DISCUSSION AND CONCLUSIONS: The trachoma control activities do not show satisfactory results, perhaps due to the prolonged duration of the treatment and follow up. The development of strategies of clinical intervention should be implemented for better control of the disease.OBJETIVO: Verificar as condições de vigilância epidemiológica do tracoma desencadeadas a partir da detecção de um caso de tracoma inflamatório na APAE - SP. MATERIAL E MÉTODO: Foram submetidos a exame ocular 1.009 pessoas entre alunos, funcionários e comunicantes intradomiciliares. Os controles de tratamento foram realizados em uma instituição, por 4 vezes, em intervalos de 45 dias. RESULTADOS: A prevalência total foi de 5,9%, sendo 5,1% de tracoma folicular (TF), 0,3% de tracoma folicular intenso (TF/TI) e 0,5% de tracoma cicatricial (TS). No primeiro controle 45,5% dos casos apresentou alta clínica e 40,0% manteve tratamento. No último controle 20,0% apresentou alta curado sem cicatrizes. A taxa de faltosos alcançou 38,2%. A distribuição espacial dos casos secundários mostrou ampla dispersão na Grande São Paulo, indicando que o tracoma deve estar disseminado por toda a região. DISCUSSÃO/CONCLUSÕES: As ações de controle do tracoma não apresentaram resultados satisfatórios, provavelmente devido ao prolongado tempo de tratamento e acompanhamento. Estratégias de intervenção clínica devem ser desenvolvidas para melhor controle da doença.Secretaria de Estado da Saúde (SES). São PauloSES. São PauloUniversidade Federal de São Paulo (UNIFESP)APAESecretaria Municipal de Saúde. São PauloUNIFESPSciEL

A importância do Plano Nacional de Fertilizantes para o futuro do agronegócio e do Brasil.

Carta da Agricultura

Seroprevalence of five neglected parasitic diseases among immigrants accessing five infectious and tropical diseases units in Italy: a cross-sectional study.

: This multicentre cross-sectional study aims to estimate the prevalence of five neglected tropical diseases (Chagas disease, filariasis, schistosomiasis, strongyloidiasis, toxocariasis) among immigrants accessing health care facilities in five Italian cities (Bologna, Brescia, Florence, Rome, Verona). : Individuals underwent a different set of serological tests, according to country of origin and presence of eosinophilia. Seropositive patients were treated and further followed up. : A total of 930 adult immigrants were enrolled: 477 men (51.3%), 445 women (47.9%), 8 transgender (0.8%); median age was 37.81 years (range 18-80). Most of them were coming from the African continent (405/930, 43.5%), the rest from East Europe, South America and Asia. A portion of 9.6% (89/930) were diagnosed with at least one of the infections under study. Seroprevalence of each specific infection varied from 3.9% (7/180) for Chagas diseases to 9.7% (11/113) for toxocariasis. Seropositive people were more likely to be 35 to 40 years-old male and to come from South East Asia, Sub-Saharan Africa or South America. : The results of our study confirm that neglected tropical diseases represent a substantial health problem among immigrants and highlight the need for addressing this emerging public health issue.<br/

Extended follow-up and impact of high-risk prognostic factors from the phase 3 RESONATE(TM) study in patients with previously treated CLL/SLL.

In the phase 3 RESONATE(TM) study, ibrutinib demonstrated superior progression-free survival (PFS), overall survival (OS), and overall response rate (ORR) compared with ofatumumab in relapsed/refractory CLL patients with high-risk prognostic factors. We report updated results from RESONATE in these traditionally chemotherapy resistant high-risk genomic subgroups at a median follow-up of 19 months. Mutations were detected by Foundation One Heme Panel. Baseline mutations in the ibrutinib arm included TP53 (51%), SF3B1 (31%), NOTCH1 (28%), ATM (19%), and BIRC3 (14%). Median PFS was not reached, with 74% of patients randomized to ibrutinib alive and progression-free at 24 months. The improved efficacy of ibrutinib vs. ofatumumab continues in all prognostic subgroups including del17p and del11q. No significant difference within the ibrutinib arm was observed for PFS across most genomic subtypes, although a subset carrying both TP53 mutation and del17p had reduced PFS compared to patients with neither abnormality. Reduced PFS or OS was not evident in patients with only del17p. PFS was significantly better for ibrutinib-treated patients in second-line vs. later lines of therapy. The robust clinical activity of ibrutinib continues to show ongoing efficacy and acceptable safety consistent with prior reports, independent of various known high-risk mutations

Vigilância epidemiológica do tracoma em instituição de ensino na cidade de São Paulo, SP

INTRODUCTION: Epidemiological surveillance activities undertaken after the detection of an active trachoma case in the APAE-SP are described. MATERIAL AND METHOD: A total of 1,009 pupils, employees and household contacts had an eye examination. Treatment control was carried out at the institution 4 times at 45 day-intervals. RESULTS: The overall prevalence was of 5.9%, 5.1% being of follicular trachoma (TF), 0.3% of intense trachoma (TF/TI) and 0.5% of cicatricial trachoma (TS). At the first control exercise 45.5% of the trachoma cases had no signs of the disease and 40.0% underwent treatment. At the last control exercise 20% were found to have been cured with no vestigial scars. Non-attendance was of 38.2%. The distribution of secondary cases showed great dispersion, suggesting dissemination throughout Greater S. Paulo . DISCUSSION AND CONCLUSIONS: The trachoma control activities do not show satisfactory results, perhaps due to the prolonged duration of the treatment and follow up. The development of strategies of clinical intervention should be implemented for better control of the disease.OBJETIVO: Verificar as condições de vigilância epidemiológica do tracoma desencadeadas a partir da detecção de um caso de tracoma inflamatório na APAE - SP. MATERIAL E MÉTODO: Foram submetidos a exame ocular 1.009 pessoas entre alunos, funcionários e comunicantes intradomiciliares. Os controles de tratamento foram realizados em uma instituição, por 4 vezes, em intervalos de 45 dias. RESULTADOS: A prevalência total foi de 5,9%, sendo 5,1% de tracoma folicular (TF), 0,3% de tracoma folicular intenso (TF/TI) e 0,5% de tracoma cicatricial (TS). No primeiro controle 45,5% dos casos apresentou alta clínica e 40,0% manteve tratamento. No último controle 20,0% apresentou alta curado sem cicatrizes. A taxa de faltosos alcançou 38,2%. A distribuição espacial dos casos secundários mostrou ampla dispersão na Grande São Paulo, indicando que o tracoma deve estar disseminado por toda a região. DISCUSSÃO/CONCLUSÕES: As ações de controle do tracoma não apresentaram resultados satisfatórios, provavelmente devido ao prolongado tempo de tratamento e acompanhamento. Estratégias de intervenção clínica devem ser desenvolvidas para melhor controle da doença

Phase Ib study of NGR–hTNF, a selective vascular targeting agent, administered at low doses in combination with doxorubicin to patients with advanced solid tumours

Contains fulltext : 81937timmer-bonte.pdf (publisher's version ) (Closed access)BACKGROUND: Asparagine-glycine-arginine-human tumour necrosis factor (NGR-hTNF) is a vascular targeting agent exploiting a tumour-homing peptide (NGR) that selectively binds to aminopeptidase N/CD13, overexpressed on tumour blood vessels. Significant preclinical synergy was shown between low doses of NGR-TNF and doxorubicin. METHODS: The primary aim of this phase I trial was to verify the safety of low-dose NGR-hTNF combined with doxorubicin in treating refractory/resistant solid tumours. Secondary objectives included pharmacokinetics (PKs), pharmacodynamics, and clinical activity. In all 15 patients received NGR-hTNF (0.2-0.4-0.8-1.6 microg m(-2)) and doxorubicin (60-75 mg m(-2)), both given intravenously every 3 weeks. RESULTS: No dose-limiting toxicity occurred and the combination was well tolerated. Around two cases of neutropenic fevers, lasting 2 days, and two cases of cardiac ejection-fraction drops, one asymptomatic and the other symptomatic, were registered. Only 11% of the adverse events were related to NGR-hTNF and were short-lasting and mild-to-moderate in severity. There was no apparent PK interaction and the shedding of soluble TNF-receptors did not increase to 0.8 microg m(-2). One partial response (7%), at dose level 0.8 microg m(-2), and 10 stable diseases (66%), lasting for a median duration of 5.6 months, were observed. CONCLUSIONS: NGR-hTNF plus doxorubicin was administered safely and showed promising activity in patients pre-treated with anthracyclines. The dose level of 0.8 microg m(-2) NGR-hTNF plus doxorubicin 75 mg m(-2) was selected for phase II development

Immunological aspects in chronic lymphocytic leukemia (CLL) development

Chronic lymphocytic leukemia (CLL) is unique among B cell malignancies in that the malignant clones can be featured either somatically mutated or unmutated IGVH genes. CLL cells that express unmutated immunoglobulin variable domains likely underwent final development prior to their entry into the germinal center, whereas those that express mutated variable domains likely transited through the germinal center and then underwent final development. Regardless, the cellular origin of CLL remains unknown. The aim of this review is to summarize immunological aspects involved in this process and to provide insights about the complex biology and pathogenesis of this disease. We propose a mechanistic hypothesis to explain the origin of B-CLL clones into our current picture of normal B cell development. In particular, we suggest that unmutated CLL arises from normal B cells with self-reactivity for apoptotic bodies that have undergone receptor editing, CD5 expression, and anergic processes in the bone marrow. Similarly, mutated CLL would arise from cells that, while acquiring self-reactivity for autoantigens—including apoptotic bodies—in germinal centers, are also still subject to tolerization mechanisms, including receptor editing and anergy. We believe that CLL is a proliferation of B lymphocytes selected during clonal expansion through multiple encounters with (auto)antigens, despite the fact that they differ in their state of activation and maturation. Autoantigens and microbial pathogens activate BCR signaling and promote tolerogenic mechanisms such as receptor editing/revision, anergy, CD5+ expression, and somatic hypermutation in CLL B cells. The result of these tolerogenic mechanisms is the survival of CLL B cell clones with similar surface markers and homogeneous gene expression signatures. We suggest that both immunophenotypic surface markers and homogenous gene expression might represent the evidence of several attempts to re-educate self-reactive B cells

Programmed Death-1 and Its Ligand Are Novel Immunotolerant Molecules Expressed on Leukemic B Cells in Chronic Lymphocytic Leukemia

Programmed death-1 (PD-1) is an immunoreceptor predominantly expressed on exhausted T cells, which through an interaction with its ligand (PD-L1), controls peripheral tolerance by limiting effector functions of T lymphocytes. qRT-PCR for PD-1, PD-L1 and their splicing forms as well as flow cytometric assessment of surface expression was performed in a cohort of 58 chronic lymphocytic leukemia (CLL) patients. In functional studies, we assessed the influence of the proliferative response of leukemic B-cells induced by IL-4 and CD40L on PD-1 transcripts and expression on the protein level. The median level of PD-1, but not PD-L1, transcripts in CLL patients was higher in comparison to healthy volunteers (HVs, n = 43, p = 0.0057). We confirmed the presence of PD-1 and PD-L1 on the CLL cell surface, and found the expression of PD-1, but not PD-L1, to be higher among CLL patients in comparison to HVs (47.2% vs. 14.8%, p<0.0001). The Kaplan-Meier curves for the time to progression and overall survival in groups with high and low surface expression of PD-1 and PD-L1 revealed no prognostic value in CLL patients. After stimulation with IL-4 and CD40L, protein expression of PD-1 was significantly increased in samples that responded and up-regulated CD38. PD-1, which is aberrantly expressed both at mRNA and cell surface levels in CLL cells might represent a novel immunotolerant molecule involved in the pathomechanism of the disease, and could provide a novel target for future therapies

Activity and safety of NGR-hTNF, a selective vascular-targeting agent, in previously treated patients with advanced hepatocellular carcinoma

Background:Hepatocellular carcinoma (HCC) is a highly vascularised and poor-prognosis tumour. NGR-hTNF is a vascular-targeting agent consisting of human tumour necrosis factor-alpha fused to the tumour-homing peptide NGR, which is able to selectively bind an aminopeptidase N overexpressed on tumour blood vessels.Methods:Twenty-seven patients with advanced-stage disease resistant to either locoregional (59%; range, 1-3), systemic treatments (52%; range, 1-3) or both (33%) received NGR-hTNF 0.8 gm-2 once every 3 weeks. The primary aim of the study was progression-free survival (PFS).Results:No grade 3-4 treatment-related toxicities were noted. Common toxicity included mild-to-moderate, short-lived chills (63%). Median PFS was 2.3 months (95% CI: 1.7-2.9). A complete response ongoing after 20 months was observed in a sorafenib-refractory patient and a partial response in a Child-Pugh class-B patient, yielding a response rate of 7%. Six patients (22%) experienced stable disease. The disease control rate (DCR) was 30% and was maintained for a median PFS time of 4.3 months. Median survival was 8.9 months (95% CI: 7.5-10.2). In a subset of 12 sorafenib-resistant patients, the response rate was 8% and the median survival was 9.5 months.Conclusion:NGR-hTNF was well tolerated and showed single-agent activity in HCC. Further investigation in HCC is of interest