Integrity and quantity of salivary cell-free DNA as a potential molecular biomarker in oral cancer: a preliminary study

Background: differences in cell-free DNA (cfDNA) fragments have been described as a valuable tool to distinguish cancer patients from healthy individuals. We aim to investigate the concentration and integrity of cfDNA fragments in saliva from oral squamous cell carcinoma (OSCC) patients and healthy individuals in order to explore their value as diagnostic biomarkers. Methods: saliva samples were collected from a total of 34 subjects (19 OSCC patients and 15 healthy controls). The total concentration of salivary cfDNA (scfDNA) was determined using a fluorometry method and quantitative real-time polymerase chain reaction (qPCR). To evaluate the scfDNA quantity and integrity, qPCR targeting Arthobacter luteus (ALU) sequences at three amplicons of different lengths (60, 115, and 247 bp, respectively) was carried out. ScfDNA integrity indexes (ALU115/ALU60 and ALU247/ALU60) were calculated as the ratio between the absolute concentration of the longer amplicons 115 bp and 247 bp and the total scfDNA amount (amplicon 60 bp).Results: the total scfDNA concentration (ALU60) was higher in OSCC than in healthy donors, but this trend was not statistically significant. The medians of scfDNA integrity indexes, ALU115/ALU60 and ALU247/ALU60, were significantly higher in OSCC, showing area under the curve values of 0.8211 and 0.7018, respectively. Conclusion: our preliminary results suggest that scfDNA integrity indexes (ALU115/ALU60 and ALU247/ALU60) have potential as noninvasive diagnostic biomarkers for OSCCS

Everolimus plus minimized tacrolimus on kidney function in liver transplantation: REDUCE, a prospective, randomized controlled study

Background and aim: reduction in calcineurin inhibitor levels is considered crucial to decrease the incidence of kidney dysfunction in liver transplant (LT) recipients. The aim of this study was to evaluate the safety and impact of everolimus plus reduced tacrolimus (EVR + rTAC) vs. mycophenolate mofetil plus tacrolimus (MMF + TAC) on kidney function in LT recipients from Spain. Methods: the REDUCE study was a 52-week, multicenter, randomized, controlled, open-label, phase 3b study in de novo LT recipients. Eligible patients were randomized (1:1) 28 days post-transplantation to receive EVR + rTAC (TAC levels <_ 5 ng/mL) or to continue with MMF + TAC (TAC levels = 6-10 ng/mL). Mean estimated glomerular filtration rate (eGFR), clinical benefit in renal function, and safety were evaluated. Results: in the EVR + rTAC group (n = 105), eGFR increased from randomization to week 52 (82.2 [28.5] mL/min/1.73 m2 to 86.1 [27.9] mL/min/1.73 m2) whereas it decreased in the MMF + TAC (n = 106) group (88.4 [34.3] mL/min/1.73 m2 to 83.2 [25.2] mL/min/1.73 m2), with significant (p < 0.05) differences in eGFR throughout the study. However, both groups had a similar clinical benefit regarding renal function (improvement in 18.6 % vs. 19.1 %, and stabilization in 81.4 % vs. 80.9 % of patients in the EVR + rTAC vs. MMF + TAC groups, respectively). There were no significant differences in the incidence of acute rejection (5.7 % vs. 3.8 %), deaths (5.7 % vs. 2.8 %), and serious adverse events (51.9 % vs. 44.0 %) between the 2 groups. Conclusion: EVR + rTAC allows a safe reduction in tacrolimus exposure in de novo liver transplant recipients, with a significant improvement in eGFR but without significant differences in renal clinical benefit 1 year after liver transplantation

The Local Volume HI Survey: Galaxy Kinematics

We present a detailed analysis of the neutral hydrogen kinematics of 12 nearby dwarf irregular galaxies observed as part of the Local Volume HI Survey (LVHIS) conducted at the Australia Telescope Compact Array. For each galaxy we measure the disk parameters (inclination, position angle) and the HI rotation curve. Six galaxies in our sample (AM0605-341, Argo Dwarf, ESO059-G001, ESO137-G018, ESO174-G?001, ESO308-G022) have their atomic hydrogen distribution studied for the first time. AM0605-341 was found to have an extension of redshifted HI which we propose is due to a tidal interaction with NGC2188. There is evidence that ESO215-G?009 has extraplanar HI gas. We also compare the global galaxy properties, in particular the integrated HI flux density and velocity widths of the observed HI spectra with the results from the low angular resolution HI Parkes All Sky Survey (HIPASS). We discuss under what circumstances the 21cm emission line profile can accurately predict the galaxy's rotation velocity, an observational parameter crucial to study the classical and baryonic Tully-Fisher relations.Comment: 22 pages, 14 figures, accepted for publication by MNRA

An objective definition for clinical suspicion of T-cell-mediated rejection after liver transplantation.

A uniform definition of clinical suspicion of T-cell-mediated rejection (TCMR) in liver transplantation (LT) is needed to homogenize clinical decisions, especially within randomized trials. This multicenter study included a total of 470 primary LT recipients. The derivation cohort consisted of 142 patients who had clinically driven liver biopsies at any time after LT. The external validation cohort included 328 patients who underwent protocol biopsies at day 7-10 after LT. The rates of moderate-severe histological TCMR were 33.8% in the derivation cohort and 43.6% in the validation cohort. Independent predictors (ie, risk factors) of moderate-severe TCMR in the derivation cohort were as follows: serum bilirubin >4 mg/dL (OR=5.83; P4 mg/dL (OR=5.83; P0.1×109 /L (OR=3.81; P=.004). In the validation cohort, the number of risk factors was an independent predictor of moderate-severe TCMR (OR=1.74; P=.001), after controlling for hepatitis C status. The number of risk factors paralleled the rates of moderate-severe TCMR in the derivation and validation cohorts (

Awake prone positioning in non-intubated patients with acute hypoxemic respiratory failure due to COVID-19: A systematic review of proportional outcomes comparing observational studies with and without awake prone positioning in the setting of COVID-19

International audienceBackground Awake prone positioning (APP) has been advocated to improve oxygenation and prevent intubations of patients with acute hypoxemic respiratory failure due to coronavirus disease 2019 (COVID-19). This paper aims to synthesize the available evidence on the efficacy of APP.Methods: We performed a systematic review of proportional outcomes from observational studies to compare intubation rate in patients treated with APP or with standard care.Results: A total of 46 published and 4 unpublished observational studies that included 2994 patients were included, of which 921 patients were managed with APP, and 870 patients were managed with usual care. APP was associated with significant improvement of oxygenation parameters in 381 cases of 19 studies that reported this outcome. Among the 41 studies assessing intubation rates (870 patients treated with APP, and 852 patients treated with usual care), the intubation rate was 27%(95%CI, 19 to 37%), as compared to 30%(95%CI, 20 to 42%)(p=0.71), even when duration of application, use of adjunctive respiratory assist device (high flow nasal cannula or non-invasive ventilation) and severity of oxygenation deficit were taken into account. There appeared to be a trend toward improved mortality when treated with APP was compared with usual care (11% v.s. 22%), which was not statistically significant.Conclusions: APP was associated with improvement of oxygenation but did not reduce the intubation rate in patients with acute respiratory failure due to COVID-19. This finding is limited by the high heterogeneity and the observational nature of included studies. Randomized controlled clinical studies are needed to definitively assess whether APP could improve key outcome such as intubation and mortality rate in these patients