The impact of 18F-FDG PET on the management of patients with suspected large vessel vasculitis

Purpose: We aimed to assess the impact of 18F-fluorodeoxyglucose (FDG) positron emission tomography (PET) on the management of patients with suspected large vessel vasculitis. Methods: An international expert panel determined diagnoses and clinical management in patients with suspected large vessel vasculitis, with and without the results of 18F-FDG PET, respectively. The accuracy of the clinical diagnosis and the resulting clinical management with and without the 18F-FDG PET results were compared using logistic regression models. Results: The analysis included 30 patients referred to a tertiary care centre with large vessel vasculitis and 31 controls. 18F-FDG PET had an overall sensitivity of 73.3% [95% confidence interval (CI) 54.1-87.7%], a specificity of 83.9% (95% CI 66.3-94.5%), a positive predictive value of 81.5% (95% CI 61.9-93.7%) and a negative predictive value of 76.5% (95% CI 58.8-89.3%). The diagnostic accuracy of 18F-FDG PET was higher in patients not receiving immunosuppressive drugs (93.3 vs 64.5%, p = 0.006). Taken in context with other available diagnostic modalities, the addition of 18F-FDG PET increased the clinical diagnostic accuracy from 54.1 to 70.5% (p = 0.04). The addition of 18F-FDG PET increased the number of indicated biopsies from 22 of 61 patients (36.1%) to 25 of 61 patients (41.0%) and changed the treatment recommendation in 8 of 30 patients (26.7%) not receiving immunosuppressive medication and in 7 of 31 patients (22.6%) receiving immunosuppressive medication. Conclusion: 18F-FDG PET is a sensitive and specific imaging tool for large vessel vasculitis, especially when performed in patients not receiving immunosuppressive drugs. It increases the overall diagnostic accuracy and has an impact on the clinical management in a significant proportion of patient

The Amelioration of Olfactory Acuity upon Sexual Maturation Might Affect Food Preferences

Upon sexual maturation, olfactory acuity in women ameliorates and starts oscillating across the cycle. During ovulation, mean olfactory threshold is 30 times lower than during bleeding. Interestingly, menstruated women undergo maleodorant trimethylaminuria. We argued that olfactory amelioration during ovulation might concur to a mating strategy, whereas olfactory impairment during bleeding might protect women against self-refusal. Testosterone and its 17β-estradiol derivative might be responsible for the synchronization of these menstrual events. Furthermore, we posed the question whether olfactory detection amelioration upon sexual maturation might provoke a change in food preferences, for instance a reduction in fish consumption. A preliminary survey in Italy provided encouraging results: 15-44 year-old women have lower fish consumption than 3-14 year-old girls. Surprisingly, men exhibited the same behaviour, so new olfactory tests as well as testosterone measurements are under way

Nucleic Acid-based Detection of Bacterial Pathogens Using Integrated Microfluidic Platform Systems

The advent of nucleic acid-based pathogen detection methods offers increased sensitivity and specificity over traditional microbiological techniques, driving the development of portable, integrated biosensors. The miniaturization and automation of integrated detection systems presents a significant advantage for rapid, portable field-based testing. In this review, we highlight current developments and directions in nucleic acid-based micro total analysis systems for the detection of bacterial pathogens. Recent progress in the miniaturization of microfluidic processing steps for cell capture, DNA extraction and purification, polymerase chain reaction, and product detection are detailed. Discussions include strategies and challenges for implementation of an integrated portable platform

Genome-wide association study of eosinophilic granulomatosis with polyangiitis reveals genomic loci stratified by ANCA status

Abstract: Eosinophilic granulomatosis with polyangiitis (EGPA) is a rare inflammatory disease of unknown cause. 30% of patients have anti-neutrophil cytoplasmic antibodies (ANCA) specific for myeloperoxidase (MPO). Here, we describe a genome-wide association study in 676 EGPA cases and 6809 controls, that identifies 4 EGPA-associated loci through conventional case-control analysis, and 4 additional associations through a conditional false discovery rate approach. Many variants are also associated with asthma and six are associated with eosinophil count in the general population. Through Mendelian randomisation, we show that a primary tendency to eosinophilia contributes to EGPA susceptibility. Stratification by ANCA reveals that EGPA comprises two genetically and clinically distinct syndromes. MPO+ ANCA EGPA is an eosinophilic autoimmune disease sharing certain clinical features and an HLA-DQ association with MPO+ ANCA-associated vasculitis, while ANCA-negative EGPA may instead have a mucosal/barrier dysfunction origin. Four candidate genes are targets of therapies in development, supporting their exploration in EGPA

The impact of 18F-FDG PET on the management of patients with suspected large vessel vasculitis

Purpose We aimed to assess the impact of 18F-fluorodeoxyglucose (FDG) positron emission tomography (PET) on the management of patients with suspected large vessel vasculitis. Methods An international expert panel determined diagnoses and clinical management in patients with suspected large vessel vasculitis, with and without the results of 18F-FDG PET, respectively. The accuracy of the clinical diagnosis and the resulting clinical management with and without the 18F-FDG PET results were compared using logistic regression models. Results The analysis included 30 patients referred to a tertiary care centre with large vessel vasculitis and 31 controls. 18F-FDG PET had an overall sensitivity of 73.3% [95% confidence interval (CI) 54.1–87.7%], a specificity of 83.9% (95% CI 66.3–94.5%), a positive predictive value of 81.5% (95% CI 61.9–93.7%) and a negative predictive value of 76.5% (95% CI 58.8–89.3%). The diagnostic accuracy of 18F-FDG PET was higher in patients not receiving immunosuppressive drugs (93.3 vs 64.5%, p?=?0.006). Taken in context with other available diagnostic modalities, the addition of 18F-FDG PET increased the clinical diagnostic accuracy from 54.1 to 70.5% (p?=?0.04). The addition of 18F-FDG PET increased the number of indicated biopsies from 22 of 61 patients (36.1%) to 25 of 61 patients (41.0%) and changed the treatment recommendation in 8 of 30 patients (26.7%) not receiving immunosuppressive medication and in 7 of 31 patients (22.6%) receiving immunosuppressive medication. Conclusion 18F-FDG PET is a sensitive and specific imaging tool for large vessel vasculitis, especially when performed in patients not receiving immunosuppressive drugs. It increases the overall diagnostic accuracy and has an impact on the clinical management in a significant proportion of patients

A Fusion of GMCSF and IL-21 Initiates Hypersignaling Through the IL-21Rα Chain With Immune Activating and Tumoricidal Effects In Vivo

We hypothesized that fusing granulocyte-macrophage colony-stimulation factor (GMCSF) and interleukin (IL)-21 as a single bifunctional cytokine (hereafter GIFT-21) would lead to synergistic anticancer immune effects because of their respective roles in mediating inflammation. Mechanistic analysis of GIFT-21 found that it leads to IL-21Rα-dependent STAT3 hyperactivation while also contemporaneously behaving as a dominant-negative inhibitor of GMCSF-driven STAT5 activation. GIFT-21's aberrant interactions with its cognate receptors on macrophages resulted in production of 30-fold greater amounts of IL-6, TNF-α, and MCP-1 when compared to controls. Furthermore, GIFT-21 treatment of primary B and T lymphocytes leads to STAT1-dependent apoptosis of IL-21Rα+ lymphocytes. B16 melanoma cells gene-enhanced to produce GIFT-21 were immune rejected by syngeneic C57Bl/6 mice comparable to the effect of IL-21 alone. However, a significant GIFT-21-driven survival advantage was seen when NOD-SCID mice were implanted with GIFT-21-secreting B16 cells, consistent with a meaningful role of macrophages in tumor rejection. Because GIFT-21 leads to apoptosis of IL-21Rα+ lymphocytes, we tested its cytolytic effect on IL-21Rα+ EL-4 lymphoma tumors implanted in C57Bl/6 mice and could demonstrate a significant increase in survival. These data indicate that GIFT-21 is a novel IL-21Rα agonist that co-opts IL-21Rα-dependent signaling in a manner permissive for targeted cancer immunotherapy