Context Pheochromocytomas and paragangliomas (PPGLs) are known to be rare. However, there is scant literature reporting their epidemiology, particularly whether the diagnosis of PPGL has increased with advances in medical imaging, biochemical and genetic testing. Objective The primary objective of this systematic review was to determine the annual incidence of PPGLs and change over time. Design A systematic review was performed. Medline, Embase, Pubmed and Web of Science Core Collection databases were searched to identify studies reporting PPGL incidence. Studies were eligible for inclusion from the database’s inception until 30th of August 2021. Results A total of 6109 manuscripts were identified; 2282 duplicates were excluded, and a further 3815 papers were excluded after abstract and/or full text review. Twelve studies were included in the final review. The incidence of PPGL ranged from 0.04 to 0.95 cases per 100,000 per year. Incidence increased over time, from approximately 0.2/100,000 individuals in studies performed prior to 2000, to approximately 0.6/100,000 in studies undertaken after 2010. The mode of diagnosis changed over the same time-period, with more patients diagnosed due to incidental imaging findings, and less at autopsy or from symptoms. Conclusion The annual incidence of PPGL has increased over time. Much of this increase is likely due to incidental identification of tumours on imaging. However, the epidemiology of PPGL remains understudied, in particular, associations with altitude, ethnicity and genetics. To improve early detection and management guidelines, these gaps should be addressed.
Gas Chromatography-Mass Spectrometry (GC-MS) has long been used for metabolite profiling of a wide range of biological samples. Many derivatisation protocols are already available and among these, trimethylsilyl (TMS) derivatisation is one of the most widely used in metabolomics. However, most TMS methods rely on off-line derivatisation prior to GC-MS analysis. In the case of manual off-line TMS derivatisation, the derivative created is unstable, so reduction in recoveries occurs over time. Thus, derivatisation is carried out in small batches. Here, we present a fully automated TMS derivatisation protocol using robotic autosamplers and we also evaluate a commercial software, Maestro available from Gerstel GmbH. Because of automation, there was no waiting time of derivatised samples on the autosamplers, thus reducing degradation of unstable metabolites. Moreover, this method allowed us to overlap samples and improved throughputs. We compared data obtained from both manual and automated TMS methods performed on three different matrices, including standard mix, wine, and plasma samples. The automated TMS method showed better reproducibility and higher peak intensity for most of the identified metabolites than the manual derivatisation method. We also validated the automated method using 114 quality control plasma samples. Additionally, we showed that this online method was highly reproducible for most of the metabolites detected and identified (RSD < 20) and specifically achieved excellent results for sugars, sugar alcohols, and some organic acids. To the very best of our knowledge, this is the first time that the automated TMS method has been applied to analyse a large number of complex plasma samples. Furthermore, we found that this method was highly applicable for routine metabolite profiling (both targeted and untargeted) in any metabolomics laboratory.
IntroductionOne in four diabetes patients will develop a foot ulcer over their lifetime. The role of glycaemic control in the healing of foot ulcers in diabetes patients is not supported by randomised controlled trial (RCT) data.ObjectivesTo determine the feasibility of an RCT of glycaemic control with intensive insulin therapy in diabetic foot ulcer, by assessing: entry criteria, fasting capillary blood glucose (FCBG) medication satisfaction and sensitivity of different ulcer-healing endpoints to glycaemic control.DesignTwo substudies: one cross-sectional and one single-arm prospective.SettingSingle-centre secondary care diabetic foot clinic in New Zealand.ParticipantsSubstudy 1: 78 participants consisting of all people ≥18 years with a diabetic foot ulcer presenting to the clinic over 35 weeks in 2015.Substudy 2: 15 participants from Substudy 1 consenting to intensive insulin therapy.InterventionSubstudy 1: None.Substudy 2: Intensive insulin therapy with standard podiatry care over 24 weeks.OutcomeSubstudy 1: Proportion of participants satisfying potential RCT entry criteria; medication satisfaction (Diabetes Medication Satisfaction).Substudy 2: FCBG, index ulcer healing time, index ulcer size, health-related quality of life (HRQoL; EuroQol 5 Dimensions 5 Levels and Diabetic Foot Ulcer Scale-Short Form).ResultsProportion in Substudy 1 satisfying all entry criteria was 31% (95% CI 21 to 42). FCBG values decreased between baseline and study end (difference −3.7 mmol/L, 95% CI −6.5 to −0.8); 83% (95% CI 44 to 95) of ulcers healed by 24 weeks. FCBG correlated negatively with medication satisfaction. Ulcer area logarithm was most sensitive to FCBG changes, displaying significant negative correlation with HRQoL outcomes. Detecting a 30% between-group difference in this outcome (80% power, α=5%) requires 220 participants per arm, achievable within 1 year with 15 centres similar to study setting.ConclusionsAn adequately powered RCT requires cooperation between a large number of centres. Ulcer area logarithm should be primary endpoint.Trial registration numberANZCTR ACTRN12617001414303
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