Long term T cell response and safety of a tetravalent dengue vaccine in healthy children.

As robust cellular responses are important for protection against dengue, this phase 2 study evaluated the kinetics and phenotype of T cell responses induced by TAK-003, a live-attenuated tetravalent dengue vaccine, in 4-16-year-old living in dengue-endemic countries (NCT02948829). Two hundred participants received TAK-003 on Days 1 and 90. Interferon-gamma (IFN-γ) enzyme-linked immunospot assay [ELISPOT] and intracellular cytokine staining were used to analyze T cell response and functionality, using peptide pools representing non-structural (NS) proteins NS3 and NS5 matching DENV-1, -2, -3, and -4 and DENV-2 NS1. One month after the second TAK-003 dose (Day 120), IFN-γ ELISPOT T cell response rates against any peptide pool were 97.1% (95% CI: 93.4% to 99.1%), and similar for baseline dengue seropositive (96.0%) and seronegative (98.6%) participants. IFN-γ ELISPOT T cell response rates at Day 120 were 79.8%, 90.2%, 77.3%, and 74.0%, against DENV-1, -2, -3, and -4, respectively, and remained elevated through 3 years post-vaccination. Multifunctional CD4 and CD8 T cell responses against DENV-2 NS peptides were observed, independent of baseline serostatus: CD8 T cells typically secreted IFN-γ and TNF-α whereas CD4 T cells secreted ≥ 2 of IFN-γ, IL-2 and TNF-α cytokines. NAb titers and seropositivity rates remained substantially elevated through 3 years post-vaccination. Overall, TAK-003 was well tolerated and elicited durable T cell responses against all four DENV serotypes irrespective of baseline serostatus in children and adolescents aged 4-16 years living in dengue-endemic countries. TAK-003-elicited CD4 and CD8 T cells were multifunctional and persisted up to 3 years post-vaccination

Miastenia grave: avaliação clinica e terapêutica de 55 casos

Foram estudados 55 casos de miastenia grave, avaliando os sinais e sintomas clínicos que ocorreram no início e na evolução dos pacientes, bem como os procedimentos diagnósticos e avaliação das medidas terapêuticas utilizadas. No manejo dos pacientes foram utilizados anticolinesterásicos, corticoesteróides, azathioprina, plasmaferese e timectomia, sem que fosse possível encontrar relação estatística significante entre os diferentes procedimentos com respeito à resolução da doença. Dos 55 casos, 9 (16,6%) obtiveram remissão total, 41 (74,5%) permaneceram com a doença ativa necessitando de tratamento sintomático e 5 (9.09%) faleceram. Houve relação estatística significante entre os sinais de insuficiência respiratória, crises miastênicas e timoma somente no grupo de pacientes que faleceram (um por insuficiência respiratória restritiva secundária a cifoescoliose severa, três com timoma e um caso durante a timectomia)

Efficacy and Safety of Three Antiretroviral Regimens for Initial Treatment of HIV-1: A Randomized Clinical Trial in Diverse Multinational Settings

Background:Antiretroviral regimens with simplified dosing and better safety are needed to maximize the efficiency of antiretroviral delivery in resource-limited settings. We investigated the efficacy and safety of antiretroviral regimens with once-daily compared to twice-daily dosing in diverse areas of the world.Methods and Findings:1,571 HIV-1-infected persons (47% women) from nine countries in four continents were assigned with equal probability to open-label antiretroviral therapy with efavirenz plus lamivudine-zidovudine (EFV+3TC-ZDV), atazanavir plus didanosine-EC plus emtricitabine (ATV+DDI+FTC), or efavirenz plus emtricitabine-tenofovir-disoproxil fumarate (DF) (EFV+FTC-TDF). ATV+DDI+FTC and EFV+FTC-TDF were hypothesized to be non-inferior to EFV+3TC-ZDV if the upper one-sided 95% confidence bound for the hazard ratio (HR) was ≤1.35 when 30% of participants had treatment failure.An independent monitoring board recommended stopping study follow-up prior to accumulation of 472 treatment failures. Comparing EFV+FTC-TDF to EFV+3TC-ZDV, during a median 184 wk of follow-up there were 95 treatment failures (18%) among 526 participants versus 98 failures among 519 participants (19%; HR 0.95, 95% CI 0.72-1.27; p = 0.74). Safety endpoints occurred in 243 (46%) participants assigned to EFV+FTC-TDF versus 313 (60%) assigned to EFV+3TC-ZDV (HR 0.64, CI 0.54-0.76; p<0.001) and there was a significant interaction between sex and regimen safety (HR 0.50, CI 0.39-0.64 for women; HR 0.79, CI 0.62-1.00 for men; p = 0.01). Comparing ATV+DDI+FTC to EFV+3TC-ZDV, during a median follow-up of 81 wk there were 108 failures (21%) among 526 participants assigned to ATV+DDI+FTC and 76 (15%) among 519 participants assigned to EFV+3TC-ZDV (HR 1.51, CI 1.12-2.04; p = 0.007).Conclusion: EFV+FTC-TDF had similar high efficacy compared to EFV+3TC-ZDV in this trial population, recruited in diverse multinational settings. Superior safety, especially in HIV-1-infected women, and once-daily dosing of EFV+FTC-TDF are advantageous for use of this regimen for initial treatment of HIV-1 infection in resource-limited countries. ATV+DDI+FTC had inferior efficacy and is not recommended as an initial antiretroviral regimen.Trial Registration:http://www.ClinicalTrials.gov NCT00084136

Aneurysmal bone cyst of the spine: Management and outcome

Study Design. The clinical records, radiographs, histologic sections, and operative reports of 52 consecutive patients with an aneurysmal bone cyst of the spine were reviewed to evaluate diagnostic and therapeutic options and to correlate treatment and outcome. Objectives. To define the incidence, clinical presentation, diagnostic and therapeutic options, and prognosis of patients with aneurysmal bone cyst of the spine. Summary of Background Data. There are special considerations in the management of spinal lesions: relative inaccessibility of the lesions, associated intraoperative bleeding, necessary of removing the entire lesion to avoid the possibility of recurrence proximity of the lesion to the spinal cord and nerve roots, and potential postoperative bony spinal instability. Methods. Fifty-two consecutive patients with an aneurysmal bone cyst of the spine were treated from 1910 to 1993. Forty patients initially treated for a primary lesion had operative treatment (19 intralesional excision and bone grafting and 21 intralesional excision), four also had adjuvant radiation therapy. Preoperative arterial embolization was performed in two. Results. There was a recurrence rate of 10% within 10 years. All recurrences were noted less than 6 months after surgery. Of 12 patients treated for a recurrent lesion two had a subsequent recurrence (16.7%) within 9 years. At last follow up examination, 50 patients (96%) were free of the disease. One patient died of postradiation osteosarcoma, and one died of intraoperative bleeding. Conclusion. Current treatment recommendations involved preoperative selective arterial embolization, intralesional excision curettage, bone grafting, and fusion of the affected area if instability is present

Performance of serum-supplemented and serum-free media in IFN gamma Elispot Assays for human T cells

The choice of serum for supplementation of media for T cell assays and in particular, Elispot has been a major challenge for assay performance, standardization, optimization, and reproducibility. The Assay Working Group of the Cancer Vaccine Consortium (CVC-CRI) has recently identified the choice of serum to be the leading cause for variability and suboptimal performance in large international Elispot proficiency panels. Therefore, a serum task force was initiated to compare the performance of commercially available serum-free media to laboratories' own medium/serum combinations. The objective of this project was to investigate whether a serum-free medium exists that performs as well as lab-own serum/media combinations with regard to antigen-specific responses and background reactivity in Elispot. In this way, a straightforward solution could be provided to address the serum challenge. Eleven laboratories tested peripheral blood mononuclear cells (PBMC) from four donors for their reactivity against two peptide pools, following their own Standard Operating Procedure (SOP). Each laboratory performed five simultaneous experiments with the same SOP, the only difference between the experiments was the medium used. The five media were lab-own serum-supplemented medium, AIM-V, CTL, Optmizer, and X-Vivo. The serum task force results demonstrate compellingly that serum-free media perform as well as qualified medium/serum combinations, independent of the applied SOP. Recovery and viability of cells are largely unaffected by serum-free conditions even after overnight resting. Furthermore, one serum-free medium was identified that appears to enhance antigen-specific IFN gamma-secretion.Experimental cancer immunology and therap