Head-To-Head Comparison of PET and Perfusion Weighted MRI Techniques to Distinguish Treatment Related Abnormalities from Tumor Progression in Glioma

The post-treatment imaging surveillance of gliomas is challenged by distinguishing tumor progression (TP) from treatment-related abnormalities (TRA). Sophisticated imaging techniques, such as perfusion-weighted magnetic resonance imaging (MRI PWI) and positron-emission tomography (PET) with a variety of radiotracers, have been suggested as being more reliable than standard imaging for distinguishing TP from TRA. However, it remains unclear if any technique holds diagnostic superiority. This meta-analysis provides a head-to-head comparison of the diagnostic accuracy of the aforementioned imaging techniques. Systematic literature searches on the use of PWI and PET imaging techniques were carried out in PubMed, Embase, the Cochrane Library, ClinicalTrials.gov and the reference lists of relevant papers. After the extraction of data on imaging technique specifications and diagnostic accuracy, a meta-analysis was carried out. The quality of the included papers was assessed using the QUADAS-2 checklist. Nineteen articles, totaling 697 treated patients with glioma (431 males; mean age ± standard deviation 50.5 ± 5.1 years) were included. The investigated PWI techniques included dynamic susceptibility contrast (DSC), dynamic contrast enhancement (DCE) and arterial spin labeling (ASL). The PET-tracers studied concerned [S-methyl- 11C]methionine, 2-deoxy-2-[ 18F]fluoro-D-glucose ([ 18F]FDG), O-(2-[ 18F]fluoroethyl)-L-tyrosine ([ 18F]FET) and 6-[ 18F]-fluoro-3,4-dihydroxy-L-phenylalanine ([ 18F]FDOPA). The meta-analysis of all data showed no diagnostic superior imaging technique. The included literature showed a low risk of bias. As no technique was found to be diagnostically superior, the local level of expertise is hypothesized to be the most important factor for diagnostically accurate results in post-treatment glioma patients regarding the distinction of TRA from TP

Protocol for Nearly Full-Length Sequencing of HIV-1 RNA from Plasma

Nearly full-length genome sequencing of HIV-1 using peripheral blood mononuclear cells (PBMC) DNA as a template for PCR is now a relatively routine laboratory procedure. However, this has not been the case when using virion RNA as the template and this has made full genome analysis of circulating viruses difficult. Therefore, a well-developed procedure for sequencing of full-length HIV-1 RNA directly from plasma was needed. Plasma from U.S. donors representing a range of viral loads (VL) was used to develop the assay. RNA was extracted from plasma and reverse-transcribed. Two or three overlapping regions were PCR amplified to cover the entire viral genome and sequenced for verification. The success of the procedure was sensitive to VL but was routinely successful for VL greater than 105 and the rate declined in proportion to the VL. While the two-amplicon strategy had an advantage of increasing the possibility of amplifying a single species of HIV-1, the three-amplicon strategy was more successful in amplifying samples with low viral loads. This protocol provides a useful tool for molecular analysis to understand the HIV epidemic and pathogenesis, as well as diagnosis, therapy and future vaccine strategies

Vemurafenib plus cobimetinib in unresectable stage IIIc or stage IV melanoma

Background: In patients with BRAFV600 mutated unresectable stage IIIc or metastatic melanoma, molecular targeted therapy with combined BRAF/MEK-inhibitor vemurafenib plus cobimetinib has shown a significantly improved progression-free survival and overall survival compared to treatment with vemurafenib alone. Nevertheless, the majority of BRAFV600 mutation-positive melanoma patients will eventually develop resistance to treatment. Molecular imaging with 18F-Fluorodeoxyglucose (18F-FDG) PET has been used to monitor response to vemurafenib in some BRAFV600 mutated metastatic melanoma patients, showing a rapid decline of 18F-FDG uptake within 2 weeks following treatment. Furthermore, preliminary results suggest that metabolic alterations might predict the development of resistance to treatment. 18F-Fluoro-3'-deoxy-3'L-fluorothymidine (18F-FLT), a PET-tracer visualizing proliferation, might be more suitable to predict response or resistance to therapy than 18F-FDG. Methods: This phase II, open-label, multicenter study evaluates whether metabolic response to treatment with vemurafenib plus cobimetinib in the first 7 weeks as assessed by 18F-FDG/18F-FLT PET can predict progression-free survival and whether early changes in 18F-FDG/18F-FLT can be used for early detection of treatment response compared to standard response assessment with RECISTv1.1 ceCT at 7 weeks. Ninety patients with BRAFV600E/K mutated unresectable stage IIIc/IV melanoma will be included. Prior to and during treatment all patients will undergo 18F-FDG PET/CT and in 25 patients additional 18F-FLT PET/CT is performed. Histopathological tumor characterization is assessed in a subset of 40 patients to unravel mechanisms of resistance. Furthermore, in all patients, blood samples are taken for pharmacokinetic analysis of vemurafenib/cobimetinib. Outcomes are correlated with PET/CT-imaging and therapy response.

An Antiretroviral/Zinc Combination Gel Provides 24 Hours of Complete Protection against Vaginal SHIV Infection in Macaques

Repeated use, coitus-independent microbicide gels that do not contain antiretroviral agents also used as first line HIV therapy are urgently needed to curb HIV spread. Current formulations require high doses (millimolar range) of antiretroviral drugs and typically only provide short-term protection in macaques. We used the macaque model to test the efficacy of a novel combination microbicide gel containing zinc acetate and micromolar doses of the novel non-nucleoside reverse transcriptase inhibitor MIV-150 for up to 24 h after repeated gel application.Rhesus macaques were vaginally challenged with SHIV-RT up to 24 h after repeated administration of microbicide versus placebo gels. Infection status was determined by measuring virologic and immunologic parameters. Combination microbicide gels containing 14 mM zinc acetate dihydrate and 50 µM MIV-150 afforded full protection (21 of 21 animals) for up to 24 h after 2 weeks of daily application. Partial protection was achieved with the MIV-150 gel (56% of control at 8 h after last application, 11% at 24 h), while the zinc acetate gel afforded more pronounced protection (67% at 8-24 h). Marked protection persisted when the zinc acetate or MIV-150/zinc acetate gels were applied every other day for 4 weeks prior to challenge 24 h after the last gel was administered (11 of 14 protected). More MIV-150 was associated with cervical tissue 8 h after daily dosing of MIV-150/zinc acetate versus MIV-150, while comparable MIV-150 levels were associated with vaginal tissues and at 24 h.A combination MIV-150/zinc acetate gel and a zinc acetate gel provide significant protection against SHIV-RT infection for up to 24 h. This represents a novel advancement, identifying microbicides that do not contain anti-viral agents used to treat HIV infection and which can be used repeatedly and independently of coitus, and underscores the need for future clinical testing of their safety and ability to prevent HIV transmission in humans

A História da Alimentação: balizas historiográficas

Os M. pretenderam traçar um quadro da História da Alimentação, não como um novo ramo epistemológico da disciplina, mas como um campo em desenvolvimento de práticas e atividades especializadas, incluindo pesquisa, formação, publicações, associações, encontros acadêmicos, etc. Um breve relato das condições em que tal campo se assentou faz-se preceder de um panorama dos estudos de alimentação e temas correia tos, em geral, segundo cinco abardagens Ia biológica, a econômica, a social, a cultural e a filosófica!, assim como da identificação das contribuições mais relevantes da Antropologia, Arqueologia, Sociologia e Geografia. A fim de comentar a multiforme e volumosa bibliografia histórica, foi ela organizada segundo critérios morfológicos. A seguir, alguns tópicos importantes mereceram tratamento à parte: a fome, o alimento e o domínio religioso, as descobertas européias e a difusão mundial de alimentos, gosto e gastronomia. O artigo se encerra com um rápido balanço crítico da historiografia brasileira sobre o tema

Axillary lymph nodes on PET in Hodgkin lymphoma after COVID‐19 vaccination

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FDG-PET/CT Limited to the Thorax and Upper Abdomen for Staging and Management of Lung Cancer.

This study evaluates the diagnostic accuracy of [F-18]-fluorodeoxyglucose-positron emission tomography/computed tomography (FDG-PET/CT) of the chest/upper abdomen compared to the generally performed scan from head to upper thighs, for staging and management of (suspected) lung cancer in patients with no history of malignancy or complaints outside the thorax.FDG-PET/CT scans of 1059 patients with suspected or recently proven lung cancer, with no history of malignancy or complaints outside the thorax, were analysed in a retrospective multi-centre trial. Suspect FDG-avid lesions in the chest and upper abdomen, the head and neck area above the shoulder line and in the abdomen and pelvis below the caudal tip of the liver were noted. The impact of lesions detected in the head and neck area and abdomen and pelvis on additional diagnostic procedures, staging and treatment decisions was evaluated.The head and neck area revealed additional suspect lesions in 7.2%, and the abdomen and pelvis in 15.8% of patients. Imaging of the head and neck area and the abdomen and pelvic area showed additional lesions in 19.5%, inducing additional diagnostic procedures in 7.8%. This resulted in discovery of additional lesions considered malignant in 10.7%, changing patient management for lung cancer in 1.2%. In (suspected) lung cancer, PET/CT limited to the chest and upper abdomen resulted in correct staging in 98.7% of patients, which led to the identical management as full field of view PET in 98.8% of patients.High value of FDG-PET/CT for staging and correct patient management is already achieved with chest and upper abdomen. Findings in head and neck area and abdomen and pelvis generally induce investigations with limited or no impact on staging and treatment of NSCLC, and can be interpreted accordingly

Additional investigations.

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Interobserver agreement of interim and end-of-treatment F-FDG PET/CT in diffuse large B-cell lymphoma (DLBCL): impact on clinical practice and trials

We aimed to assess the interobserver agreement of interim PET (I-PET) and end-of-treatment PET (EoT-PET) using the Deauville score (DS) in first-line diffuse large B-cell lymphoma (DLBCL) patients. Methods: I-PET and EoT-PET scans of DLBCL patients were performed in the HOVON84 study (2007–2012), an international multicenter randomized controlled trial. Patients received R-CHOP14 and were randomized to receive rituximab intensification in the first 4 cycles or not. I-PET was performed after 4 cycles (for observational purposes), and EoT-PET after 6 or 8 cycles. Two independent central reviewers retrospectively scored all scans according to the DS system, masked to clinical outcomes. Results were dichotomized as negative (DS of 1–3) or positive (DS of 4–5). Besides percentage overall agreement (OA), we calculated agreement for positive and negative scores, expressed as positive agreement (PA) and negative agreement (NA), respectively. Results: 465 I-PET and 457 EoT-PET scans were centrally reviewed; baseline18F-FDG PET or PET/CT was available in 75%–77%, and CT in the remaining cases. Percentage OA for I-PET and EoT-PET were 87.7% and 91.7% (P 5 0.049), with NA of 92.0% and 95.0% (P 5 0.091), and PA of 73.7% and 76.3% (P 5 0.656), respectively. Conclusion: Interobserver agreement using DS in DLBCL patients in I-PET and EoT-PET yields high OA and NA. The lower PA suggests that EoT-PET/CT treatment evaluation in daily practice and I-PET–adapted trials may benefit from dual reads and central review, respectively

Interobserver agreement of interim and end-of-treatment F-FDG PET/CT in diffuse large B-cell lymphoma (DLBCL): impact on clinical practice and trials

We aimed to assess the interobserver agreement of interim PET (I-PET) and end-of-treatment PET (EoT-PET) using the Deauville score (DS) in first-line diffuse large B-cell lymphoma (DLBCL) patients. Methods: I-PET and EoT-PET scans of DLBCL patients were performed in the HOVON84 study (2007–2012), an international multicenter randomized controlled trial. Patients received R-CHOP14 and were randomized to receive rituximab intensification in the first 4 cycles or not. I-PET was performed after 4 cycles (for observational purposes), and EoT-PET after 6 or 8 cycles. Two independent central reviewers retrospectively scored all scans according to the DS system, masked to clinical outcomes. Results were dichotomized as negative (DS of 1–3) or positive (DS of 4–5). Besides percentage overall agreement (OA), we calculated agreement for positive and negative scores, expressed as positive agreement (PA) and negative agreement (NA), respectively. Results: 465 I-PET and 457 EoT-PET scans were centrally reviewed; baseline18F-FDG PET or PET/CT was available in 75%–77%, and CT in the remaining cases. Percentage OA for I-PET and EoT-PET were 87.7% and 91.7% (P 5 0.049), with NA of 92.0% and 95.0% (P 5 0.091), and PA of 73.7% and 76.3% (P 5 0.656), respectively. Conclusion: Interobserver agreement using DS in DLBCL patients in I-PET and EoT-PET yields high OA and NA. The lower PA suggests that EoT-PET/CT treatment evaluation in daily practice and I-PET–adapted trials may benefit from dual reads and central review, respectively