Impact of remnant vital tissue after locoregional treatment and liver transplant in hepatocellular cancer patients,a multicentre cohort study

The role of pathological findings after locoregional treatments as predictors of hepatocellular cancer recurrence after liver transplantation has been poorly addressed. The aim of the study was to identify the role of remnant vital tissue (RVT) of the target lesion in predicting hepatocellular cancer recurrence. Two hundred and seventy‐six patients firstly undergoing locoregional treatment and then transplanted between January 2010 and December 2015 in four European Transplant Centres (i.e. Rome Tor Vergata, Birmingham, Brussels and Ancona) were enrolled in the study to investigate the role of pathological response at upfront locoregional treatment. At multivariable Cox regression analysis, RVT ≥2 cm was a strong independent risk factor for post‐LT recurrence (HR = 5.6; P < 0.0001). Five‐year disease‐free survival rates were 60.8%, 80.9% and 95.0% in patients presenting a RVT ≥2 cm vs. 0.1–1.9 vs. no RVT, respectively. When only Milan Criteria‐IN patients were analysed, similar results were reported, with 5‐year disease‐free survival rates of 58.1%, 79.0% and 94.0% in patients presenting a RVT ≥2 cm vs. 0.1–1.9 vs. no RVT, respectively. RVT is an important determinant of tumour recurrence after liver transplantation performed for hepatocellular cancer. Its discriminative power looks to be evident also in a Milan‐IN setting, suggesting to more liberally use locoregional treatments also in these patients.     

Bedside assessment of the effects of positive end-expiratory pressure on lung inflation and recruitment by the helium dilution technique and electrical impedance tomography

Purpose

Higher positive end-expiratory pressure might induce lung inflation and recruitment, yielding enhanced regional lung protection. We measured positive end-expiratory pressure-related lung volume changes by electrical impedance tomography and by the helium dilution technique. We also used electrical impedance tomography to assess the effects of positive end-expiratory pressure on regional determinants of ventilator-induced lung injury.

Methods

A prospective randomized crossover study was performed on 20 intubated adult patients: 12 with acute hypoxemic respiratory failure and 8 with acute respiratory distress syndrome. Each patient underwent protective controlled ventilation at lower (7 [7, 8] cmH₂O) and higher (12 [12, 13] cmH₂O) positive end-expiratory pressures. At the end of each phase, we collected ventilation, helium dilution, and electrical impedance tomography data.

Results

Positive end-expiratory pressure-induced changes in lung inflation and recruitment measured by electrical impedance tomography and helium dilution showed close correlations (R ² = 0.78, p < 0.001 and R ² = 0.68, p < 0.001, respectively) but with relatively variable limits of agreement. At higher positive end-expiratory pressure, recruitment was evident in all lung regions (p < 0.01) and heterogeneity of tidal ventilation distribution was reduced by increased tidal volume distending the dependent lung (p < 0.001); in the non-dependent lung, on the other hand, compliance decreased (p < 0.001) and tidal hyperinflation significantly increased (p < 0.001). In the subgroup of ARDS patients (but not in the whole study population) tidal hyperinflation in the dependent lung regions decreased at higher positive end-expiratory pressure (p = 0.05), probably indicating higher potential for recruitment.

Conclusions

Close correlations exist between bedside assessment of positive end-expiratory pressure-induced changes in lung inflation and recruitment by the helium dilution and electrical impedance tomography techniques. Higher positive end-expiratory pressure exerts mixed effects on the regional determinants of ventilator-induced lung injury; these merit close monitoring.

     

Electrophysiological Modulation in an Effort to Complete Illusory Figures: Configuration,Illusory Contour and Closure Effects

Figure recognition process: From the coarse configuration standing from the background to the closure of a meaningful shape, was investigated by ERP technique. ERP components at different latencies from stimulus onset allowed to tap into the figure recognition process at discrete time-points when different cognitive operations take place. In this study, we present two experiments where the support-ratio (SR) of illusory figures was manipulated to vary continuously the recognition of geometrical figures. In the first experiment three shapes were used to vary the SR and the P1 component (80–130 ms) was modulated by the configuration-effect explained, in part for the first time, with the unbalanced physical stimulation between upper and lower visual field. In the second experiment, we used one shape and varied systematically the SR in a discrimination task. The N1 (130–180 ms) and the N2 (230–270 ms) were modulated by two effects: The Ic-effect, represented by the N1, and the closure-effect, represented by the N2, being larger when the SR was small and the discrimination more difficult with respect to large SRs and easier discrimination. These results showed that figure recognition proceeded from the coarse parsing of the visual scene (configuration-effect), through the completion of a set of illusory borders (Ic-effect) to the final assembling of a meaningful shape (closure-effect).     

MDCT of the liver in obese patients: evaluation of a different method to optimize iodine dose

Purpose

To prospectively compare two different approaches for estimating the amount of intravenous contrast media (CM) needed for multiphasic MDCT of the liver in obese patients.

Materials and methods

This single-center, HIPAA-compliant prospective study was approved by our Institutional Review Board. Ninety-six patients (55 men, 41 women), with a total of 42 hypovascular liver lesions, underwent MDCT of the liver. The amount of contrast medium injected was computed according to the patient’s lean body weight which was estimated using either a bioimpedance device (Group A) or the James formula (Group B). The following variables were compared between the two groups: the amount of contrast medium injected (in grams of Iodine, gI), the contrast enhancement index (CEI) and the lesion-to-liver contrast-to-noise ratio.

Results

Protocols A and B yielded significant differences in the amount of CM injected (mean values 41.9 ± 4.41 gI in Group A vs. 35.9 ± 5.75 gI in Group B; P = 0.021). The mean CEI value and lesion-to-liver contrast-to-noise ratio measured on the portal phase were significantly higher with protocol A than with protocol B (P < 0.05).

Conclusions

Our study shows that the adoption of a bioimpedance device in obese patients improves liver parenchymal enhancement and lesion conspicuity.

     

Quantitative measurement and control of oxygen levels in microfluidic poly(dimethylsiloxane) bioreactors during cell culture

Microfluidic bioreactors fabricated from highly gas-permeable poly(dimethylsiloxane) (PDMS) materials have been observed, somewhat unexpectedly, to give rise to heterogeneous long term responses along the length of a perfused mammalian cell culture channel, reminiscent of physiologic tissue zonation that arises at least in part due to oxygen gradients. To develop a more quantitative understanding and enable better control of the physical-chemical mechanisms underlying cell biological events in such PDMS reactors, dissolved oxygen concentrations in the channel system were quantified in real time using fluorescence intensity and lifetime imaging of an oxygen sensitive dye, ruthenium tris(2,2’-dipyridyl) dichloride hexahydrate (RTDP). The data indicate that despite oxygen diffusion through PDMS, uptake of oxygen by cells inside the perfused PDMS microchannels induces an axial oxygen concentration gradient, with lower levels recorded in downstream regions. The oxygen concentration gradient generated by a balance of cellular uptake, convective transport by media flow, and permeation through PDMS in our devices ranged from 0.0003 (mg/l)/mm to 0.7 (mg/l)/mm. The existence of such steep gradients induced by cellular uptake can have important biological consequences. Results are consistent with our mathematical model and give insight into the conditions under which flux of oxygen through PDMS into the microchannels will or will not contribute significantly to oxygen delivery to cells and also provide a design tool to manipulate and control oxygen for cell culture and device engineering. The combination of computerized microfluidics, in situ oxygen sensing, and mathematical models opens new windows for microphysiologic studies utilizing oxygen gradients and low oxygen tensions. Electronic Supplementary Material is available in the online version of this article at     

Selenium exposure and the risk of type 2 diabetes: a systematic review and meta-analysis

In 2007, supplementation with the trace element selenium in a trial was unexpectedly found to be associated with an excess risk of type 2 diabetes. Given the concerns raised by these findings and the large number of recent studies on this topic, we reviewed the available literature with respect to this possible association. In this paper, we assessed the results of both experimental and nonexperimental epidemiologic studies linking selenium with type 2 diabetes incidence. Through a systematic literature search, we retrieved 50 potentially eligible nonexperimental studies and 5 randomized controlled trials published through June 11, 2018. To elucidate the possible dose–response relation, we selected for further analysis those studies that included multiple exposure levels and serum or plasma levels. We computed a pooled summary risk ratio (RR) of diabetes according to selenium exposure in these studies. We also computed a RR for diabetes incidence following supplementation with 200 µg/day of selenium compared with placebo in trials. In the nonexperimental studies, we found a direct relation between selenium exposure and risk of diabetes, with a clear and roughly linear trend in subjects with higher plasma or serum selenium levels, with RR at 140 µg/L of selenium exposure compared with a referent category of?<?45 µg/L equal to 3.6 [95% confidence interval (CI) 1.4–9.4]. A dose–response meta-analysis focusing on studies with direct assessment of dietary selenium intake showed a similar trend. In experimental studies, selenium supplementation increased the risk of diabetes by 11% (RR 1.11, 95% CI 1.01–1.22) compared with the placebo-allocated participants, with a higher RR in women than in men. Overall, results from both nonexperimental and experimental studies indicate that selenium may increase the risk of type 2 diabetes across a wide range of exposure levels. The relative increase in risk is small but of possible public health importance because of the high incidence of diabetes and the ubiquity of selenium exposure.     

Use of N-terminal pro-brain natriuretic peptide to detect acute cardiac dysfunction during weaning failure in difficult-to-wean patients with chronic obstructive pulmonary disease

OBJECTIVE: To evaluate the utility of serial measurements of plasma N-terminal pro-brain natriuretic peptide (NT-proBNP) to detect acute cardiac dysfunction during weaning failure in difficult to wean patients with chronic obstructive pulmonary disease. DESIGN: Prospective observational cohort study. SETTING: A 14-bed general intensive care unit in a university hospital. PATIENTS: Nineteen patients mechanically ventilated for chronic obstructive pulmonary disease exacerbation who were difficult to wean. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Cardiac and hemodynamic variables, arterial and central venous blood gas, breathing pattern, respiratory mechanics, indexes of oxygen cost of breathing, and plasma levels of NT-proBNP were measured and analyzed immediately before (baseline) and at the end of a spontaneous breathing trial. Eight of 19 patients (42%) were identified with acute cardiac dysfunction at the end of the weaning trial. Baseline NT-proBNP levels were significantly higher (median 5000, interquartile range 4218 pg/mL) in these patients than in patients without evidence of acute cardiac dysfunction (median 1705, interquartile range 3491 pg/mL). Plasma levels of NT-proBNP increased significantly at the end of the spontaneous breathing trial only in patients with acute cardiac dysfunction (median 12,733, interquartile range 16,456 pg/mL, p < .05). The elevation in NT-proBNP at the end of the weaning trial had a good diagnostic performance in detecting acute cardiac dysfunction, as estimated by area under the receiver operating characteristic curve analysis (area under the curve 0.909, se 0.077, 95% confidence interval 0.69-0.98; p < .0001, cutoff = 184.7 pg/mL). CONCLUSIONS: Serial measurements of NT-proBNP plasma levels provided a noninvasive manner to detect acute cardiac dysfunction during an unsuccessful weaning trial in difficult to wean patients with chronic obstructive pulmonary disease. The utility of this test as a complement of the standard clinical monitoring of the weaning trial deserves further investigation.