Scientific reports
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Malnutrition is common in patients with acute kidney injury (AKI) and the risk of mortality is high, especially if renal replacement therapy is needed. Between April 2013 through April 2014, we recruited critically ill adult patients (≥18 years) with severe AKI in two University hospitals in London, UK, and measured serial plasma concentrations of vitamin B1, B6, B12, C and D, folate, selenium, zinc, copper, iron, carnitine and 22 amino acids for six consecutive days. In patients receiving continuous renal replacement therapy (CRRT), the concentrations of the same nutrients in the effluent were also determined. ⋯ All amino acids, trace elements, vitamin C and folate were detectable in effluent fluid. In >30% of CRRT and non-CRRT patients, the plasma nutrient concentrations of zinc, iron, selenium, vitamin D3, vitamin C, trytophan, taurine, histidine and hydroxyproline were below the reference range throughout the 6-day period. In conclusion, altered micronutrient status is common in patients with severe AKI regardless of treatment with CRRT.
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MUC5B rs35705950 (G/T) is strongly associated with idiopathic pulmonary fibrosis (IPF) and also contributes to the risk of interstitial lung disease (ILD) in rheumatoid arthritis (RA-ILD) and chronic hypersensitivity pneumonitis (CHP). Due to this, we evaluated the implication of MUC5B rs35705950 in antisynthetase syndrome (ASSD), a pathology characterised by a high ILD incidence. 160 patients with ASSD (142 with ILD associated with ASSD [ASSD-ILD+]), 232 with ILD unrelated to ASSD (comprising 161 IPF, 27 RA-ILD and 44 CHP) and 534 healthy controls were genotyped. MUC5B rs35705950 frequency did not significantly differ between ASSD-ILD+ patients and healthy controls nor when ASSD patients were stratified according to the presence/absence of anti Jo-1 antibodies or ILD. ⋯ However, a statistically significant decrease of MUC5B rs35705950 GT, TT and T frequencies in ASSD-ILD+ patients compared to patients with ILD unrelated to ASSD was observed. In summary, our study does not support a role of MUC5B rs35705950 in ASSD. It also indicates that there are genetic differences between ILD associated with and that unrelated to ASSD.
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End-expiratory occlusion test (EEOT) has been proposed as a preload responsiveness test that overcomes several limitations of pulse pressure (PPV) and stroke volume (SVV) variations. We compared the ability of EEOT versus SVV and PPV to predict fluid responsiveness during the increase of the vasomotor tone in a rabbit model of hemorrhage. Ten rabbits were anesthetized, paralyzed, and mechanically ventilated during basal load (BL), after progressive blood withdrawal (BW), and after volume replacement. ⋯ PHE induced a significant decrease of PPV and SVV, but without affecting ∆SVEEOT, and ∆AoFEEOT. We conclude that ∆SV and ∆AoF during EEOT kept the ability to predict fluid responsiveness during PHE infusion in a rabbit hemorrhage model. This result may suggest the advantage of EEOT with respect to SVV and PPV in predicting fluid responsiveness during vasomotor tone increase.
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Arising from the ablation of the cytoskeletal protein dystrophin, Duchenne Muscular Dystrophy (DMD) is a debilitating and fatal skeletal muscle wasting disease underpinned by metabolic insufficiency. The inability to facilitate adequate energy production may impede calcium (Ca2+) buffering within, and the regenerative capacity of, dystrophic muscle. Therefore, increasing the metabogenic potential could represent an effective treatment avenue. ⋯ These effects were independent of upregulated utrophin expression in the tibialis anterior. ASA treatment also increased mitochondrial viability in mdx flexor digitorum brevis fibres and concomitantly reduced O2- production, an effect that was also observed in cultured immortalised human DMD myoblasts. Our data indicates that ASA has a protective effect on mdx skeletal muscles.
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Human trophoblast cell-surface marker (Trop-2) is a surface glycoprotein originally identified in human placental tissue and subsequently found to be highly expressed by various types of human epithelial solid tumors. We investigated the efficacy of sacituzumab govitecan, an antibody-drug conjugate (ADC) comprised of a humanized anti- Trop-2 antibody, conjugated with active metabolite of irinotecan (SN-38), on Trop-2 positive cervical cancer cell lines and a xenograft model. Trop-2 expression was evaluated in 147 primary cervical tumors by immunohistochemistry, real-time polymerase chain reaction, and flow cytometry. ⋯ In xenografts, a significant tumor growth inhibition was seen after twice-weekly intravenous administration of the drug for three weeks (p < 0.0001, and p = 0.001 for sacituzumab govitecan vs naked antibody, and sacituzumab govitecan vs control-ADC, respectively). Overall survival at 90 days was significantly improved in the sacituzumab govitecan group (p = 0.014). In conclusion, sacituzumab govitecan may represent a novel targeted therapy option in cervical cancer patients overexpressing Trop-2.