FDG-PET/CT discriminates between patients with and without lymphomas in primary Sjögren's syndrome

OBJECTIVES: To assess the usefulness of FDG-PET/CT 1) to discriminate between pSS patients with and without lymphomas and 2) to evaluate systemic disease activity in pSS.METHODS: ACR-EULAR-positive pSS patients who underwent FDG-PET/CT were included. Scans were visually evaluated and quantitative analysis was performed by measuring standardized uptake values (SUV) of salivary and lacrimal glands and systemic regions. ROC analyses were performed to find SUV cut-off values to discriminate between lymphoma and non-lymphoma.RESULTS: 26 of the 70 included patients were diagnosed with a pSS-associated lymphoma, mostly of the mucosa associated lymphoid tissue type (23/26). Lymphoma patients showed higher FDG-uptake in the parotid and submandibular glands, and more frequently showed presence of nodular lung lesions, compared with non-lymphoma patients. The accuracy of the maximum SUV (SUVmax) in the parotid and submandibular gland to predict lymphoma diagnosis was good, with optimal cut-off points of 3.1 and 2.9. After combining these three visual and quantitative findings (nodular lung lesions, parotid SUVmax &gt; 3.1 and submandibular SUVmax &gt; 2.9), sensitivity was 92% when at least one of the three features were present, and specificity was 91% in case at least two features were present. Furthermore, FDG-PET/CT was able to detect systemic manifestations in pSS patients, mostly involving lymph nodes, entheses and lungs.CONCLUSIONS: FDG-PET/CT can assist in excluding pSS-associated lymphomas in patients without PET abnormalities, possibly leading to a decrease of invasive biopsies in suspected lymphoma patients. Furthermore, FDG-PET/CT is able to detect systemic manifestations in pSS and can guide to the best biopsy location.</p

FDG-PET/CT discriminates between patients with and without lymphomas in primary Sjögren's syndrome

OBJECTIVES: To assess the usefulness of FDG-PET/CT 1) to discriminate between pSS patients with and without lymphomas and 2) to evaluate systemic disease activity in pSS.METHODS: ACR-EULAR-positive pSS patients who underwent FDG-PET/CT were included. Scans were visually evaluated and quantitative analysis was performed by measuring standardized uptake values (SUV) of salivary and lacrimal glands and systemic regions. ROC analyses were performed to find SUV cut-off values to discriminate between lymphoma and non-lymphoma.RESULTS: 26 of the 70 included patients were diagnosed with a pSS-associated lymphoma, mostly of the mucosa associated lymphoid tissue type (23/26). Lymphoma patients showed higher FDG-uptake in the parotid and submandibular glands, and more frequently showed presence of nodular lung lesions, compared with non-lymphoma patients. The accuracy of the maximum SUV (SUVmax) in the parotid and submandibular gland to predict lymphoma diagnosis was good, with optimal cut-off points of 3.1 and 2.9. After combining these three visual and quantitative findings (nodular lung lesions, parotid SUVmax &gt; 3.1 and submandibular SUVmax &gt; 2.9), sensitivity was 92% when at least one of the three features were present, and specificity was 91% in case at least two features were present. Furthermore, FDG-PET/CT was able to detect systemic manifestations in pSS patients, mostly involving lymph nodes, entheses and lungs.CONCLUSIONS: FDG-PET/CT can assist in excluding pSS-associated lymphomas in patients without PET abnormalities, possibly leading to a decrease of invasive biopsies in suspected lymphoma patients. Furthermore, FDG-PET/CT is able to detect systemic manifestations in pSS and can guide to the best biopsy location.</p

FDG-PET/CT discriminates between patients with and without lymphomas in primary Sjögren's syndrome

OBJECTIVES: To assess the usefulness of FDG-PET/CT 1) to discriminate between pSS patients with and without lymphomas and 2) to evaluate systemic disease activity in pSS.METHODS: ACR-EULAR-positive pSS patients who underwent FDG-PET/CT were included. Scans were visually evaluated and quantitative analysis was performed by measuring standardized uptake values (SUV) of salivary and lacrimal glands and systemic regions. ROC analyses were performed to find SUV cut-off values to discriminate between lymphoma and non-lymphoma.RESULTS: 26 of the 70 included patients were diagnosed with a pSS-associated lymphoma, mostly of the mucosa associated lymphoid tissue type (23/26). Lymphoma patients showed higher FDG-uptake in the parotid and submandibular glands, and more frequently showed presence of nodular lung lesions, compared with non-lymphoma patients. The accuracy of the maximum SUV (SUVmax) in the parotid and submandibular gland to predict lymphoma diagnosis was good, with optimal cut-off points of 3.1 and 2.9. After combining these three visual and quantitative findings (nodular lung lesions, parotid SUVmax &gt; 3.1 and submandibular SUVmax &gt; 2.9), sensitivity was 92% when at least one of the three features were present, and specificity was 91% in case at least two features were present. Furthermore, FDG-PET/CT was able to detect systemic manifestations in pSS patients, mostly involving lymph nodes, entheses and lungs.CONCLUSIONS: FDG-PET/CT can assist in excluding pSS-associated lymphomas in patients without PET abnormalities, possibly leading to a decrease of invasive biopsies in suspected lymphoma patients. Furthermore, FDG-PET/CT is able to detect systemic manifestations in pSS and can guide to the best biopsy location.</p

FDG-PET/CT discriminates between patients with and without lymphomas in primary Sjögren's syndrome

OBJECTIVES: To assess the usefulness of FDG-PET/CT 1) to discriminate between pSS patients with and without lymphomas and 2) to evaluate systemic disease activity in pSS.METHODS: ACR-EULAR-positive pSS patients who underwent FDG-PET/CT were included. Scans were visually evaluated and quantitative analysis was performed by measuring standardized uptake values (SUV) of salivary and lacrimal glands and systemic regions. ROC analyses were performed to find SUV cut-off values to discriminate between lymphoma and non-lymphoma.RESULTS: 26 of the 70 included patients were diagnosed with a pSS-associated lymphoma, mostly of the mucosa associated lymphoid tissue type (23/26). Lymphoma patients showed higher FDG-uptake in the parotid and submandibular glands, and more frequently showed presence of nodular lung lesions, compared with non-lymphoma patients. The accuracy of the maximum SUV (SUVmax) in the parotid and submandibular gland to predict lymphoma diagnosis was good, with optimal cut-off points of 3.1 and 2.9. After combining these three visual and quantitative findings (nodular lung lesions, parotid SUVmax &gt; 3.1 and submandibular SUVmax &gt; 2.9), sensitivity was 92% when at least one of the three features were present, and specificity was 91% in case at least two features were present. Furthermore, FDG-PET/CT was able to detect systemic manifestations in pSS patients, mostly involving lymph nodes, entheses and lungs.CONCLUSIONS: FDG-PET/CT can assist in excluding pSS-associated lymphomas in patients without PET abnormalities, possibly leading to a decrease of invasive biopsies in suspected lymphoma patients. Furthermore, FDG-PET/CT is able to detect systemic manifestations in pSS and can guide to the best biopsy location.</p

FDG-PET/CT discriminates between patients with and without lymphomas in primary Sjögren's syndrome

OBJECTIVES: To assess the usefulness of FDG-PET/CT 1) to discriminate between pSS patients with and without lymphomas and 2) to evaluate systemic disease activity in pSS.METHODS: ACR-EULAR-positive pSS patients who underwent FDG-PET/CT were included. Scans were visually evaluated and quantitative analysis was performed by measuring standardized uptake values (SUV) of salivary and lacrimal glands and systemic regions. ROC analyses were performed to find SUV cut-off values to discriminate between lymphoma and non-lymphoma.RESULTS: 26 of the 70 included patients were diagnosed with a pSS-associated lymphoma, mostly of the mucosa associated lymphoid tissue type (23/26). Lymphoma patients showed higher FDG-uptake in the parotid and submandibular glands, and more frequently showed presence of nodular lung lesions, compared with non-lymphoma patients. The accuracy of the maximum SUV (SUVmax) in the parotid and submandibular gland to predict lymphoma diagnosis was good, with optimal cut-off points of 3.1 and 2.9. After combining these three visual and quantitative findings (nodular lung lesions, parotid SUVmax &gt; 3.1 and submandibular SUVmax &gt; 2.9), sensitivity was 92% when at least one of the three features were present, and specificity was 91% in case at least two features were present. Furthermore, FDG-PET/CT was able to detect systemic manifestations in pSS patients, mostly involving lymph nodes, entheses and lungs.CONCLUSIONS: FDG-PET/CT can assist in excluding pSS-associated lymphomas in patients without PET abnormalities, possibly leading to a decrease of invasive biopsies in suspected lymphoma patients. Furthermore, FDG-PET/CT is able to detect systemic manifestations in pSS and can guide to the best biopsy location.</p

Low Mutational Burden of Extranodal Marginal Zone Lymphoma of Mucosa-Associated Lymphoid Tissue in Patients with Primary Sjogren's Syndrome

SIMPLE SUMMARY: Patients with primary Sjogren’s syndrome (pSS) are at risk of developing extranodal marginal zone lymphoma (ENMZL) of the mucosa-associated lymphoid tissue (MALT) in the parotid glands. The genetic mechanism underlying development of MALT lymphoma in the context of pSS is unknown. The aim of our study was to define the genomic landscape of pSS-associated MALT lymphoma. For 17 localized pSS-associated MALT lymphomas, we analyzed the presence of nonsynonymous mutations, copy number alterations (CNAs) and MALT1 translocations. pSS-associated MALT lymphomas were characterized by a low mutational load (median number of nonsynonymous somatic variants per case was 7, range 2–78) and a limited number of CNAs. Unlike the recurrent genomic aberrations observed in MALT lymphoma, which were not associated with pSS, pSS-associated MALT lacked a clear lymphoma-related profile. The data suggest that localized pSS-associated MALT lymphomas are a distinct type of ENMZL, which are genomically stable and most likely depend on a stimulatory micro-environment. ABSTRACT: Patients with primary Sjogren’s syndrome (pSS) are at risk of developing extranodal marginal zone lymphoma (ENMZL) of the mucosa-associated lymphoid tissue (MALT) in the parotid glands. Unlike recurrent genomic aberrations observed in MALT lymphoma, which were not associated with pSS (non-pSS), it is unknown which somatic aberrations underlie the development of pSS-associated MALT lymphomas. Whole-exome sequencing was performed on 17 pSS-associated MALT lymphomas. In total, 222 nonsynonymous somatic variants affecting 182 genes were identified across the 17 cases. The median number of variants was seven (range 2–78), including three cases with a relatively high mutational load (≥24/case). Out of 16 recurrently mutated genes, ID3, TBL1XR1, PAX5, IGLL5 and APC are known to be associated with lymphomagenesis. A total of 18 copy number alterations were detected in eight cases. MALT1 translocations were not detected. With respect to outcome, only two cases relapsed outside of the salivary glands. Both had a high mutational load, suggesting a more advanced stage of lymphoma. The low mutational load and lack of a clear lymphoma-related mutation profile suggests that localized pSS-associated MALT lymphomas are genomically more stable than non-pSS MALT lymphomas and most likely depend on a stimulatory micro-environment

Adverse outcome pathways:opportunities, limitations and open questions

Adverse outcome pathways (AOPs) are a recent toxicological construct that connects, in a formalized, transparent and quality-controlled way, mechanistic information to apical endpoints for regulatory purposes. AOP links a molecular initiating event (MIE) to the adverse outcome (AO) via key events (KE), in a way specified by key event relationships (KER). Although this approach to formalize mechanistic toxicological information only started in 2010, over 200 AOPs have already been established. At this stage, new requirements arise, such as the need for harmonization and re-assessment, for continuous updating, as well as for alerting about pitfalls, misuses and limits of applicability. In this review, the history of the AOP concept and its most prominent strengths are discussed, including the advantages of a formalized approach, the systematic collection of weight of evidence, the linkage of mechanisms to apical end points, the examination of the plausibility of epidemiological data, the identification of critical knowledge gaps and the design of mechanistic test methods. To prepare the ground for a broadened and appropriate use of AOPs, some widespread misconceptions are explained. Moreover, potential weaknesses and shortcomings of the current AOP rule set are addressed (1) to facilitate the discussion on its further evolution and (2) to better define appropriate vs. less suitable application areas. Exemplary toxicological studies are presented to discuss the linearity assumptions of AOP, the management of event modifiers and compensatory mechanisms, and whether a separation of toxicodynamics from toxicokinetics including metabolism is possible in the framework of pathway plasticity. Suggestions on how to compromise between different needs of AOP stakeholders have been added. A clear definition of open questions and limitations is provided to encourage further progress in the field

Fisheries compliance in South Africa: A decade of challenges and reform 1994-2004

In South Africa, fishery managers have struggled with a number of challenges in terms of compliance amidst a process of legal and policy reform since the democratic elections of 1994. The past 10 years, and more specifically the past five, have seen a significant change in compliance effort, with a particular focus on increasing law enforcement activities and capacity. This paper highlights two case studies that have been instrumental in restructuring fisheries compliance in South Africa. Although law enforcement has been significantly strengthened, greater political will and government commitment is required to implement alternative strategies that will have a long-term impact on levels of compliance.Fisheries compliance Law enforcement Voluntary compliance

Compliance review: A study undertaken to support the development of a Regional MCS Strategy for Pacific Oceanic Fisheries

The achievement of FFA members’ regional goals for their tuna fisheries depends heavily upon the effective implementation by national governments of a comprehensive range of MCS measures. In support of this, FFA members have established various regional MCS measures that provide a framework to enable effective management and control of the region’s tuna fisheries. However, problematic implementation at the national level continues to undermine the ability of FFA members and the secretariat to fully implement these initiatives and effectively monitor and control the region’s tuna fisheries, thereby threatening their returns. While some FFA members have developed strong MCS systems with high levels of implementation, much of the FFA membership continues to suffer from inconsistent implementation of MCS measures. Various studies have identified the need to improve MCS implementation, noting that weaknesses in MCS were critical obstacles to sustainable management and profitable development.. This is no simple task for any country – developed or developing; island or continent. In 2006, an international study assessed compliance by 53 countries (95% of global fish landings) with key provisions of the Code of Conduct for Responsible Fisheries. The study noted that approximately 57% of the countries ‘failed’ on compliance with MCS related measures. Of these, 30% had particularly poor ‘fail’ grades, including the regionally significant countries: France, Philippines, China, Indonesia, Taiwan, and Spain. Project Two reviews the implementation by FFA members of MCS measures and provides recommendations for improving performance and monitoring where necessary. This review focuses primarily on implementation of regional and global MCS measures that have been agreed to by the FFA membership