Search

Introduction and Objectives: Endoscopic ultrasound guided portal pressure gradient measurement (EUS-PPGm) would provide useful clinical information in patients with liver diseases. However, there is yet scarcely data on the clinical relevance of this EUS-guided procedure.We report our experience on EUS-PPGm focus on safety, clinical relevant findings, technical drawbacks and how to overcome them, aiming to make this procedure more safe, accurate and available. Materials and Patients: EUS-PPGm was performed with a therapeutic echoendoscope and a dedicated 25G needle in 30 consecutive patients. Assessment of NAFLD 25; idiopathic portal hypertension 3; evaluation for curative therapy in hepatocellular carcinoma (HCC) 2. EUS-guided bilobar liver biopsies (EUS-BLB) were also immediately performed in 26 patients (87%) with a 19G needle Results: EUS-PPGm was obtained in 25/30 patients (83%) being >5 mmHg in 10/22 NALFD patients (45%) without endoscopic and/or ultrasonographic signs of portal hypertension neither liver fibrosis on EUS-BLB. Mean time to obtain EUS-PPGm was 21±2 minutes.EUS-PPGm was not obtained in 5 cases. In 4 cases for excesive use of the elevator and up&down wheel and bending of the needle. In another case for exacerbating breathing movements. The hepatic and portal vein were difficult to punction in one and two cases, respectively having to transverse the vessels and reposition the needle.A self-limited bleeding from the cardias and a mild epigastric pain 2 day after a combined procedure were observed without other adverse events one month later. Conclusions: EUS-guided PPGm, even when combined with EUS-BLB, seems safe providing useful clinical information. Almost half of patients affected with NAFLD have portal hypertension diagnosed precociously in reversible stages providing a useful tool in precision Medicine, especially in the setting of obesity pandemic. There are technical aspects related to the needle and the position of the echoendoscope that should be known to improve the safety, accuracy and availibility of this procedure.

ABSTRACT Therapeutic options to treat bacterial infections caused by Gram-negative pathogens are limited due to the spread of multidrug resistance. Protein engineering of phage-derived lysins can play a key role in the search for new antimicrobial compounds targeting Gram-negative pathogens. A previous high-throughput screen of a combinatorial lysin library identified lysin 1D10 active against Acinetobacter baumannii under elevated human serum concentrations. The engineered lysin consists of four modules: cecropin A, a linker, cell wall-binding domain, and an enzymatic active domain. Using time-lapse microscopy, we show that 1D10 has a distinct antibacterial mode of action resulting in local cell wall bulging at the septum instead of cell-wide lysis, as observed for previously reported engineered lysins that target Gram-negative bacteria. Our results indicate that the activity of 1D10 relies on the antibacterial activity of both cecropin A (CecA) and the enzymatically active domain. Based on a truncation analysis, the role of each of the four modules of 1D10 was dissected. We further compared the antibacterial spectrum, thermostability, and cytotoxicity of cecropin A alone and lysin 1D10. Both lysin 1D10 and CecA are most active against A. baumannii and are not cytotoxic toward human keratinocytes. Lysin 1D10 unfolds at 57°C and has a remarkable refolding capacity, as it regains its activity even after exposure to 90°C and sterilization conditions, whereas CecA is inactivated at 70°C. Overall, the present study shows that an improved understanding of the killing mechanism and the protein properties will further support lysin engineering designs in the future. IMPORTANCE Engineered lysins are considered as highly promising alternatives for antibiotics. Our previous screening study using VersaTile technology identified 1D10 as a possible lead compound with activity against Acinetobacter baumannii strains under elevated human serum concentrations. In this manuscript, we reveal an unexpected mode of action and exceptional thermoresistance for lysin 1D10. Our findings shed new light on the development of engineered lysins, providing valuable insights for future research in this field.

Objectives: The course of progressive liver damage after achieving sustained virological response (SVR) with direct-acting antivirals (DAAs) remains undetermined. We aimed to determine risk factors associated with the development of liver-related events (LREs) after SVR, focusing on the utility of non-invasive markers. Methods: An observational, retrospective study that included patients with advanced chronic liver disease (ACLD) caused by hepatitis C virus (HCV), who achieved SVR with DAAs between 2014 and 2017. Patients were followed-up until December 2020. LREs were defined as the development of portal hypertension decompensation and the occurrence of hepatocellular carcinoma (HCC). Serological markers of fibrosis were calculated before treatment and one and two years after SVR. Results: The study included 321 patients, with a median follow-up of 48 months. LREs occurred in 13.7% of patients (10% portal hypertension decompensation and 3.7% HCC). Child–Pugh [HR 4.13 (CI 95% 1.74; 9.81)], baseline FIB-4 [HR 1.12 (CI 95% 1.03; 1.21)], FIB-4 one year post-SVR [HR 1.31 (CI 95% 1.15; 1.48)] and FIB-4 two years post-SVR [HR 1.42 (CI 95% 1.23; 1.64)] were associated with portal hypertension decompensation. Older age, genotype 3, diabetes mellitus and FIB-4 before and after SVR were associated with the development of HCC. FIB-4 cut-off values one and two years post-SVR to predict portal hypertension decompensation were 2.03 and 2.21, respectively, and to predict HCC were 2.42 and 2.70, respectively. Conclusions: HCV patients with ACLD remain at risk of developing liver complications after having achieved SVR. FIB-4 evaluation before and after SVR may help to predict this risk, selecting patients who will benefit from surveillance.

This prospective single-center study was designed to assess the clinical utility of the FilmArray® blood culture identification (BCID) panel for improving the diagnostic accuracy in neonatal sepsis. Results obtained using the FilmArray® BCID panel were correlated with results of blood culture in all consecutive neonates with suspicion of early-onset (EOS) and late-onset sepsis (LOS) attended in our service over a two-year period. A total of 102 blood cultures from 92 neonates were included, 69 (67.5%) in cases of EOS and 33 (32.3%) in LOS. The FilmArray® BCID panel was performed in negative culture bottles at a median of 10 h of blood culture incubation (IQR 8–20), without differences by the type of sepsis. The FilmArray® BCID panel showed a 66.7% sensitivity, 100% specificity, 100% positive predictive value, and 95.7% negative predictive value. There were four false-negative cases, three of which were Streptococcus epidermidis in neonates with LOS, and there was one case of Granulicatella adiacens in one neonate with EOS. We conclude that the use of the FilmArray® BCID panel in negative blood cultures from neonates with clinical suspicion of sepsis is useful in decision-making of starting or early withdrawal of empirical antimicrobials because of the high specificity and negative predictive values of this assay.

The prevalence of postnatal growth faltering (PGF) in preterm infants with very low birth weight (VLBW) (n = 112; and 2013–2017, n = 92) were compared. Results. In the second five-year period, a decrease in prevalence of PGF was observed (36.6% vs. 22.8%, p = 0.033), an increase in growth rate in the first 28 days (5.22 (4.35–6.09) g/kg/day vs. 11.38 (10.61–12.15) g/kg/day, p < 0.0001) and an increase in height standard deviation (SD) at 2 years (−1.12 (−1.35–−0.91) vs. −0.74 (−0.99–−0.49) p = 0.023). Probability of short stature at 2 years was directly related to daily weight gain in the first 28 days. Conclusions: when comparing two five-year periods in the last two decades, growth in VLBW preterm infants has improved, both during neonatal period and at two years of age.

The tasks workers perform on the job are informative about the direction and the impact of technological change. We harmonize occupational task-content measures between two worker-level surveys, which separately cover developing and developed countries. Developing countries use routine-cognitive tasks and routine-manual tasks more intensively than developed countries, but less intensively use non-routine analytical tasks and non-routine interpersonal tasks. This is partly because developing countries have more workers in occupations with high routine content and fewer workers in occupations with high non-routine content. More importantly, a given occupation has more routine content and less non-routine content in developing countries than in developed countries. Since 2006, occupations with high non-routine content gained employment relative to those with high routine content in most countries, regardless of their income level or initial task intensity, indicating the global reaches of the technological change that reduces the demand for occupations with high routine content. [ABSTRACT FROM AUTHOR]