18F-FDG PET/CT for diagnosing infectious complications in patients with severe neutropenia after intensive chemotherapy for haematological malignancy or stem cell transplantation

Item does not contain fulltextPURPOSE: Between 30 and 50% of febrile neutropenic episodes are accounted for by infection. C-reactive protein (CRP) is a nonspecific parameter for infection and inflammation but might be employed as a trigger for diagnosis. The aim of the study was to evaluate whether (18)F-fluorodeoxyglucose (FDG) positron emission tomography (PET)/CT can be used to detect inflammatory foci in neutropenic patients with elevated CRP and whether it helps to direct treatment. METHODS: Twenty-eight consecutive patients with neutropenia as a result of intensive chemotherapy for haematological malignancies or myeloablative therapy for haematopoietic stem cell transplantation were prospectively included. (18)F-FDG PET/CT was added to the regular diagnostic workup once the CRP level rose above 50 mg/l. RESULTS: Pathological FDG uptake was found in 26 of 28 cases despite peripheral neutrophil counts less than 0.1 x 10(-9)/l in 26 patients: in the digestive tract in 18 cases, around the tract of the central venous catheter (CVC) in 9 and in the lungs in 7 cases. FDG uptake in the CVC tract was associated with coagulase-negative staphylococcal bacteraemia (p < 0.001) and deep venous thrombosis (p = 0.002). The number of patients having Streptococcus mitis bacteraemia appeared to be higher in patients with grade 3 oesophageal FDG uptake (p = 0.08). Pulmonary FDG uptake was associated with the presence of invasive fungal disease (p = 0.04). CONCLUSION: (18)F-FDG PET/CT scanning during chemotherapy-induced febrile neutropenia and increased CRP is able to detect localized foci of infection and inflammation despite the absence of circulating neutrophils. Besides its potential role in detecting CVC-related infection during febrile neutropenia, the high negative predictive value of (18)F-FDG PET/CT is important for avoiding unnecessary diagnostic tests and therapy.1 januari 201

Cancer metabolism: current perspectives and future directions

Cellular metabolism influences life and death decisions. An emerging theme in cancer biology is that metabolic regulation is intricately linked to cancer progression. In part, this is due to the fact that proliferation is tightly regulated by availability of nutrients. Mitogenic signals promote nutrient uptake and synthesis of DNA, RNA, proteins and lipids. Therefore, it seems straight-forward that oncogenes, that often promote proliferation, also promote metabolic changes. In this review we summarize our current understanding of how ‘metabolic transformation' is linked to oncogenic transformation, and why inhibition of metabolism may prove a cancer′s ‘Achilles' heel'. On one hand, mutation of metabolic enzymes and metabolic stress sensors confers synthetic lethality with inhibitors of metabolism. On the other hand, hyperactivation of oncogenic pathways makes tumors more susceptible to metabolic inhibition. Conversely, an adequate nutrient supply and active metabolism regulates Bcl-2 family proteins and inhibits susceptibility to apoptosis. Here, we provide an overview of the metabolic pathways that represent anti-cancer targets and the cell death pathways engaged by metabolic inhibitors. Additionally, we will detail the similarities between metabolism of cancer cells and metabolism of proliferating cells

Impact and Effectiveness of the Quadrivalent Human Papillomavirus Vaccine: A Systematic Review of 10 Years of Real-world Experience

Prophylactic human papillomavirus (HPV) vaccination programs constitute major public health initiatives worldwide. We assessed the global effect of quadrivalent HPV (4vHPV) vaccination on HPV infection and disease. PubMed and Embase were systematically searched for peer-reviewed articles from January 2007 through February 2016 to identify observational studies reporting the impact or effectiveness of 4vHPV vaccination on infection, anogenital warts, and cervical cancer or precancerous lesions. Over the last decade, the impact of HPV vaccination in real-world settings has become increasingly evident, especially among girls vaccinated before HPV exposure in countries with high vaccine uptake. Maximal reductions of approximately 90% for HPV 6/11/16/18 infection, approximately 90% for genital warts, approximately 45% for low-grade cytological cervical abnormalities, and approximately 85% for high-grade histologically proven cervical abnormalities have been reported. The full public health potential of HPV vaccination is not yet realized. HPV-related disease remains a significant source of morbidity and mortality in developing and developed nations, underscoring the need for HPV vaccination programs with high population coverage

Quantitative trait loci for steady-state platelet count in mice

Platelet count in humans is a strongly genetically regulated trait, with approximately 85% of the interindividual variance in platelet numbers attributable to genetic factors. Inbred mouse strains also have strain-specific platelet count ranges. As part of a project to identify novel factors that regulate platelet count, we identified two inbred mouse strains, CBA/CaH and QSi5, with substantial differences in platelet count (mean values of 581 vs. 1062 × 109/L). An F2 intercross resource of 1126 animals was bred from these two parental strains for a genomewide scan for quantitative trait loci (QTL) for platelet count. QTL were identified on MMU1 (LOD 6.8, p < 0.0005) and MMU11 (LOD 11.2, p < 0.0005) by selectively genotyping animals from the extremes of the F2 platelet count distribution. Three other QTL of suggestive statistical significance were also detected on MMU7, 13, and 17. It is noteworthy that no QTL were detected in the vicinity of the genes encoding thrombopoietin (Thpo), and its receptor (c-Mpl), both known to influence platelet production. Comparison of gene expression levels between the parental mouse strains by microarrays also showed little difference in the mRNA levels of these known candidate genes. These results represent the first published use of a genetic linkage-based approach in a mouse model toward the identification of genetic factors that regulate platelet count