No abstract

The COVID-19 pandemic has been the primary global health issue since its outbreak in December 2019. Patients with metabolic syndrome suffer from severe complications and a higher mortality rate due to SARS-CoV-2 infection. We recently proposed that SARS-CoV-2 can hijack host mitochondrial function and manipulate metabolic pathways for their own advantage. The aim of the current study was to investigate functional mitochondrial changes in live peripheral blood mononuclear cells (PBMCs) from COVID-19 patients, decipher the pathways of substrate utilization in these cells and corresponding changes in the inflammatory pathways. We demonstrate mitochondrial dysfunction, metabolic alterations with an increase in glycolysis and high levels of mitokine in PBMCs from COVID-19 patients. Interestingly, we found that levels of FGF-21 mitokine correlate with COVID-19 disease severity and mortality. These data suggest that COVID-19 patients have compromised mitochondrial function and an energy deficit which is compensated by a metabolic switch to glycolysis. This metabolic manipulation by SARS-CoV-2 triggers an enhanced inflammatory response which contributes to severity of symptoms in COVID-19. Targeting mitochondrial metabolic pathway(s) can help define novel strategies for COVID-19.

Introduction: Pancreatic cystic neoplasms consist of mucinous cystic neoplasms (MCNs) and serous cystic neoplasms (SCNs). MCNs have significantly greater malignant potential, and if resected early the prognosis is excellent, although mortality is 2-3%. Endoscopic ultrasound is a minimally invasive and well tolerated procedure. EUS with fine-needle aspiration (EUS-FNA) provides samples for cytology and fluid analysis, a major advantage over other techniques. However the diagnostic accuracy of EUS-FNA is highly variable in published studies. Aim: To determine the diagnostic accuracy of EUS-FNA to differentiate mucinous versus non-mucinous cystic lesions with morphology, and cyst fluid analysis for cytology and carcinoembryonic antigen (CEA) via a meta-analysis of published studies. Methods: Relevant studies were identified using MEDLINE and included if they used a reference standard of definitive surgical pathology or clinical follow-up (≥6 months). Study quality was assessed using the STARD (STAndards for the Reporting of Diagnostic Accuracy) initiative criteria. Data was analysed using Meta-DiSc© v.1.4, which generated pooled estimates for sensitivity, specificity and summary ROC curve. Subgroups, determined a priori, were used to assess heterogeneity: prospective vs. retrospective, location, number of centres and patients, 19G or 22G needle and STARD score. Results: Twenty-four studies published between 2001 and 2011 were included, a total of 1703 patients. The median number of patients in each study was 53 (range 18-197) and the median study length was 54 (12-144) months. The pooled sensitivities (95% CI) and specificities (95% CI) and area under the sROC curve (Standard Error), respectively, were: EUS morphology 55 (49-61)%, 65 (57-72)% and 0.74 (0.095); Cytology 54(50-59)%, 93(90-95)% and 0.95 (0.040); and CEA 63(59-67)%, 88(83-91)% and 0.79 (0.034). Subgroup analysis indicated that retrospective design, low STARD score and study location outside Europe were significant sources of heterogeneity. Conclusion: Fine-needle aspiration has moderate sensitivity but high specificity resulting in good overall diagnostic accuracy for mucinous cystic neoplasms. Morphology alone is inadequate for distinguishing cystic lesions but may contribute to the assessment of more advanced lesions. The moderate sensitivity of FNA (54%) means a significant proportion of MCNs will not be detected. However, the high specificity (93%) means that a positive result is strongly indicative of a mucinous cystic neoplasm. Thus, EUS-FNA is a useful diagnostic tool for correct identification of MCNs and may be the gold standard for pre-operative assessment.

A targeted reversed-phase gradient UPLC-MS/MS assay has been developed for the quantification /monitoring of 66 amino acids and amino-containing compounds in human plasma and serum using precolumn derivatization with 6-aminoquinolyl-N-hydroxysuccinimidyl carbamate (AccQTag Ultra). Derivatization of the target amines required minimal sample preparation and resulted in analytes with excellent chromatographic and mass spectrometric detection properties. The resulting method, which requires only 10 μL of sample, provides the reproducible and robust separation of 66 analytes in 7.5 min, including baseline resolution of isomers such as leucine and isoleucine. The assay has been validated for the quantification of 33 amino compounds (predominantly amino acids) over a concentration range from 2 to 20 and 800 μM. Intra- and interday accuracy of between 0.05 and 15.6 and 0.78-13.7% and precision between 0.91 and 16.9% and 2.12-15.9% were obtained. A further 33 biogenic amines can be monitored in samples for relative changes in concentration rather than quantification. Application of the assay to samples derived from healthy controls and patients suffering from acetaminophen (APAP, paracetamol)-induced acute liver failure (ALF) showed significant differences in the amounts of aromatic and branched chain amino acids between the groups as well as a number of other analytes, including the novel observation of increased concentrations of sarcosine in ALF patients. The properties of the developed assay, including short analysis time, make it suitable for high-throughput targeted UPLC-ESI-MS/MS metabonomic analysis in clinical and epidemiological environments.