Headspace-solid phase microextraction gas chromatography-mass spectrometry (HS-SPME-GC-MS) can be used to measure volatile organic compounds (VOCs) in human urine. However, there is no widely adopted standardised protocol for the preparation of urine samples for analysis resulting in an inability to compare studies reliably between laboratories. This paper investigated the effect of altering urine sample pH, volume, and vial size for optimising detection of VOCs when using HS-SPME-GC-MS. This is the first, direct comparison of H2SO4, HCl, and NaOH as treatment techniques prior to HS-SPME-GC-MS analysis. Altering urine sample pH indicates that H2SO4 is more effective at optimising detection of VOCs than HCl or NaOH. H2SO4 resulted in a significantly larger mean number of VOCs being identified per sample (on average, 33.5 VOCs to 24.3 in HCl or 12.2 in NaOH treated urine) and more unique VOCs, produced a more diverse range of classes of VOCs, and led to less HS-SPME-GC-MS degradation. We propose that adding 0.2 mL of 2.5 M H2SO4 to 1 mL of urine within a 10 mL headspace vial is the optimal sample preparation prior to HS-SPME-GC-MS analysis. We hope the use of our optimised method for urinary HS-SPME-GC-MS analysis will enhance our understanding of human disease and bolster metabolic biomarker identification.

Background and Aims Feed intolerance (FI) is common in cirrhosis patients in intensive care units (ICU). Prokinetics are the first line treatment for FI but their efficacy and safety in critically ill patient with cirrhosis is unknown. We evaluated the role of prokinetics in reversal of FI and clinical outcomes. Methods Consecutive patients admitted in ICU developing new-onset FI, were randomized to receive either intravenous metoclopramide (Gr.A, n = 28), erythromycin (Gr.B, n = 27) or placebo (Gr.C, n = 28). FI was defined with the presence of 3 of 5 variables- absence of bowel sounds, gastric residual volume ≥ 500 ml, vomiting, diarrhoea and bowel distension. Primary end-point was complete resolution of FI (≥ 3 variables resolved) within 24-h and secondary end-points included resolution within 72-h and survival at 7-days. Results Of the 1030 ICU patients, 201 (19.5%) developed FI and 83 patients were randomized. Baseline parameters between the groups were comparable. Complete resolution at 24-h was higher in Gr.A (7.14%) and B (22.2%) than C (0%, p = 0.017). Overall, 58 (69.9%) patients achieved resolution within 72 h, more with metoclopramide ( n = 24, 85.7%) and erythromycin ( n = 25, 92.6%) than with placebo ( n = 9, 32.1%, p < 0.001). The 7-day survival was better in patients who achieved resolution within 72-h (65.5 vs. 36%, p = 0.011) than non-responders. High lactate (OR-3.32, CI-1.45–7.70, p = 0.005), shock at baseline (OR-6.34, CI-1.67–24.1, p = 0.007) and resolution of FI within 72 h (OR-0.11, CI, 0.03–0.51, p = 0.04) predicted 7-day mortality. Conclusions FI is common in critically-ill cirrhosis patients and non-resolution carries high mortality. Early recognition and treatment with prokinetics is recommended to improve short-term survival.

This paper presents an improved low voltage cascode and flipped voltage follower (FVF) based current mirror with the enhancement of the bandwidth obtained by using a compensation resistor between the gates of the primary transistor pair. In this technique a carefully determined resistance is used in the diode connected MOS transistor of the current mirror for enhancing the bandwidth. Active realization of the compensation resistance using MOS operating in the triode region has also been applied to both the cascode and FVF based current mirror circuits. The proposed circuits have been simulated using PSpice for 0.25 lm CMOS technology and the obtained results are compared with their uncompensated topologies to show their effectiveness.

Predicting when a patient with advanced cancer is dying is a challenge and currently no prognostic test is available. We hypothesised that a dying process from cancer is associated with metabolic changes and specifically with changes in volatile organic compounds (VOCs). We analysed urine from patients with lung cancer in the last weeks of life by headspace gas chromatography mass spectrometry. Urine was acidified or alkalinised before analysis. VOC changes in the last weeks of life were identified using univariate, multivariate and linear regression analysis; 12 VOCs increased (11 from the acid dataset, 2 from the alkali dataset) and 25 VOCs decreased (23 from the acid dataset and 3 from the alkali dataset). A Cox Lasso prediction model using 8 VOCs predicted dying with an AUC of 0.77, 0.78 and 0.85 at 30, 20 and 10 days and stratified patients into a low (median 10 days), medium (median 50 days) or high risk of survival. Our data supports the hypothesis there are specific metabolic changes associated with the dying. The VOCs identified are potential biomarkers of dying in lung cancer and could be used as a tool to provide additional prognostic information to inform expert clinician judgement and subsequent decision making.

cholangiopathy. [ 18 F]-fluorodeoxyglucose positron emission tomography/computed tomography (FDG PET/CT) is the only technique that allows imaging of metabolic activity by detecting FDG accumulation in cells and correlation with anatomical structures. Increased tracer uptake is typically seen in inflammatory or neoplastic tissue thereby potentially aiding diagnosis, and assessment of disease extent and activity. There is limited data currently available on its utility in IgG4-RD and whether this varies according to presentation. The aim of this study is to determine the utility of FDG PET/CT in diagnosis, monitoring disease activity and identifying multi system involvement. Methods We performed a retrospective study of a prospectively maintained multi-disciplinary IgG4-RD database to identify patients who underwent FDG PET/CT over a 3year period. Additional organ involvement and change in management consequent on FDG PET/CT was recorded. Fisher's exact test was used for the comparison of proportions.Results 25 patients with a diagnosis or suspicion of IgG4-RD underwent FDG PET/CT between November 2016 and October 2019. The median age [IQR] at presentation was 59 [48.5-65.5], 18 (72%) were male. 15 (72.5%) suspected or proven PB disease, 6 (24%) head and neck (HN), 1 (4%) each of retroperitoneal, both PB and HN, pulmonary and renal. In 22 (88%) cases (15/15 PB, 7/10 non PB) FDG PET/CT findings had a direct impact on management. The difference in utility between PB (100%) and non-PB (70%) was not quite statistically significant (p=0.059). In 1 patient it enabled exclusion of PB IgG4-RD. In 15 (60%) it led to a decision to escalate therapy this included 3 AIP cases (21.4% of definite PB cases) in which new organ involvement was identified. In 6 cases (5 PB and 1 renal IgG4-RD) with concern of active disease because of persistently elevated or rising IgG4 levels it excluded FDG avid inflammation. ConclusionIn this retrospective study FDG PET/CT had a clinically important impact on management of IgG4-RD. Identifying other organ involvement as well as influencing therapeutic decision making particularly in PB disease. Further studies are required to fully delineate its role in IgG4-RD.