Interobserver agreement in contrast harmonic endoscopic ultrasound.

BACKGROUND AND AIM: Contrast harmonic endoscopic ultrasound (CH-EUS) was recently introduced to clinical practice; its reproducibility among endosonographers is unknown. Our aim was to assess the interobserver agreement (IA) in CH-EUS. METHODS: Fifteen endosonographers (eight experienced and seven non-experienced) from 11 Italian EUS centers evaluated 80 video-cases (40 solid pancreatic lesions, 20 pancreatic cystic lesions and 20 submucosal lesions) of CH-EUS, according to the degree of enhancement, the pattern of distribution and the washout of the contrast agent. IA within each group and between the two groups of observers was assessed with the Fleiss kappa statistic. RESULTS: Overall IA was moderate for the uptake and fair for the pattern of distribution and the washout. In solid pancreatic lesions, IA was moderate for the uptake and fair for the pattern and the washout. In cystic pancreatic lesions, IA was uniformly moderate for the assessment of uptake, slight for the pattern and fair for the washout. In submucosal tumors, IA was substantial for the uptake, slight for the pattern and fair for the washout. Non-experienced endosonographers demonstrated, in most cases, comparable IA with the experienced ones. CONCLUSIONS: Interobserver agreement among endosonographers for CH EUS was satisfactory. In particular, overall IA varied from slight to substantial, being fair in the majority of cases. Inherent structural features of the lesions, as well as technical differences between the variables assessed, could have accounted for the fluctuation of the results. Outcomes of IA were reproducible between experienced and non-experienced endosonographers.

Investigation of Streptomyces antibioticus tyrosinase reactivity toward chlorophenols.

Tyrosinase (Ty) is a copper-containing enzyme ubiquitously distributed in nature. In recent years, Ty has attracted interest as a potential detoxifying agent for xenobiotic compounds with phenolic structure. Among these, chlorophenols are particularly relevant pollutants, commonly found in waste waters. The activity of Streptomyces antibioticus tyrosinase toward isomeric monochlorophenols was studied. Tyrosinase oxidizes both 3- and 4-chlorophenol to the same product, 4-chloro-1,2-ortho-quinone, which subsequently undergoes a nucleophilic substitution reaction at the chlorine atom by excess phenol to give the corresponding phenol-quinone adduct. By contrast, 2-chlorophenol is not reactive and acts as a competitive inhibitor. Docking calculations suggest that the substrates point to one of the copper atoms of the dinuclear center (copper B) and appear to interact preferentially with one of the two coordinated oxygen atoms. The approach of the substrate toward the active site is favored by a π-stacking interaction with one of the copper-coordinated histidines (His194) and by a hydrogen bonding interaction with the O1 oxygen. With this study, we provide the first characterization of the early intermediates in the biotechnologically relevant reaction of Ty with chlorophenols. Additionally, combining experimental evidences with molecular modeling simulations, we propose a detailed reaction scheme for Ty-mediated oxidation of monochlorophenols.

Identification of Health Expenditures Determinants: A Model to Manage the Economic Burden of Cardiovascular Disease.

The purpose of this paper is to investigate the determinants influencing the costs of cardiovascular disease in the regional health service in Italy's Apulia region from 2014 to 2016. Data for patients with acute myocardial infarction (AMI), heart failure (HF), and atrial fibrillation (AF) were collected from the hospital discharge registry. Generalized linear models (GLM), and generalized linear mixed models (GLMM) were used to identify the role of random effects in improving the model performance. The study was based on socio-demographic variables and disease-specific variables (diagnosis-related group, hospitalization type, hospital stay, surgery, and economic burden of the hospital discharge form). Firstly, both models indicated an increase in health costs in 2016, and lower spending values for women (p < 0.001) were shown. GLMM indicates a significant increase in health expenditure with increasing age (p < 0.001). Day-hospital has the lowest cost, surgery increases the cost, and AMI is the most expensive pathology, contrary to AF (p < 0.001). Secondly, AIC and BIC assume the lowest values for the GLMM model, indicating the random effects' relevance in improving the model performance. This study is the first that considers real data to estimate the economic burden of CVD from the regional health service's perspective. It appears significant for its ability to provide a large set of estimates of the economic burden of CVD, providing information to managers for health management and planning.

Structural equation modeling to shed light on the controversial role of climate on the spread of SARS-CoV-2.

Climate seems to influence the spread of SARS-CoV-2, but the findings of the studies performed so far are conflicting. To overcome these issues, we performed a global scale study considering 134,871 virologic-climatic-demographic data (209 countries, first 16 weeks of the pandemic). To analyze the relation among COVID-19, population density, and climate, a theoretical path diagram was hypothesized and tested using structural equation modeling (SEM), a powerful statistical technique for the evaluation of causal assumptions. The results of the analysis showed that both climate and population density significantly influence the spread of COVID-19 (p < 0.001 and p < 0.01, respectively). Overall, climate outweighs population density (path coefficients: climate vs. incidence = 0.18, climate vs. prevalence = 0.11, population density vs. incidence = 0.04, population density vs. prevalence = 0.05). Among the climatic factors, irradiation plays the most relevant role, with a factor-loading of - 0.77, followed by temperature (- 0.56), humidity (0.52), precipitation (0.44), and pressure (0.073); for all p < 0.001. In conclusion, this study demonstrates that climatic factors significantly influence the spread of SARS-CoV-2. However, demographic factors, together with other determinants, can affect the transmission, and their influence may overcome the protective effect of climate, where favourable.

Contrast harmonic echo-endoscopic ultrasound improves accuracy in diagnosis of solid pancreatic masses.

BACKGROUND & AIMS: Contrast harmonic echo (CHE) has been developed for endoscopic ultrasound (EUS). This new technique detects echo signals from microbubbles in vessels with very slow flow, without artifacts. We assessed whether CHE-EUS increases the accuracy of diagnosis of pancreatic solid lesions. METHODS: At a tertiary-care EUS center, we examined 90 patients who were suspected of having pancreatic solid neoplasm. Radial and linear echoendoscopes were used with dedicated software for CHE. Sonovue (Bracco International BV, Amsterdam, The Netherlands) uptake, pattern, and washout were studied; data were compared for pancreatic lesions and adjacent parenchyma. The final diagnosis was obtained based on results of surgical pathology and/or EUS-fine needle aspiration (FNA) analyses. RESULTS: The finding of a hypoenhancing mass with an inhomogeneous pattern was a sensitive and accurate identifier of patients with adenocarcinoma (96% and 82%, respectively) (49 of 51 patients with primary pancreatic adenocarcinoma had a hypoenhancing mass that was inhomogeneous and had fast washout). This finding was more accurate in diagnosis than the finding of a hypoechoic lesion using standard EUS (P < .000). Hyperenhancement specifically excluded adenocarcinoma (98%), although sensitivity was low (39%). Of neuroendocrine tumors, 11 of 13 were non-hypo-enhancing (9 hyperenhancing, 2 isoenhancing). Interestingly, CHE-EUS allowed detection of small lesions in 7 patients who had uncertain standard EUS findings because of biliary stents (n = 5) or chronic pancreatitis (n = 2). Targeted EUS-FNA was performed on these lesions. CONCLUSIONS: Detection of a hypoenhancing and inhomogeneous mass accurately identified patients with pancreatic adenocarcinoma. CHE-EUS increased the detection of malignant lesions in difficult cases (patients with chronic pancreatitis or biliary stents) and helped guide EUS-FNA. A hyperenhancing pattern could be used to rule out adenocarcinoma.

CO 2 vs. air insufflation in endoscopic ultrasonography: a prospective study.

Background and study aims Carbon dioxide (CO 2 ) is being increasingly used for insufflation during endoscopy for safety and better tolerance. The role of CO 2 during endoscopic ultrasonography (EUS) has not been studied yet. Our main aim was to compare the effects of CO 2 vs. air insufflation on abdominal discomfort in patients undergoing EUS. Our secondary outcomes were to ascertain the effects of CO 2 insufflation on image quality/visual artifacts and on the amount of sedation. Patients and methods This was a prospective, controlled, single-blind, observational study. Abdominal discomfort was assessed before diagnostic EUS, and 1 and 3 hours post-procedure and recorded as a visual analogue scale. Image quality was also recorded as a 4-point scale from optimal to poor at four different scanning sites (esophagus, stomach, duodenal bulb and second portion). Results A total of 198 patients were enrolled. We observed that CO 2 resulted in less abdominal discomfort than air insufflation that was statistically significant at 3 hours ( P  = 0.048) but not at 1 hour after EUS ( P  = 0.112), probably due to the ongoing effects of sedation at the latter stage. On the other hand, no differences were found in the dose of sedation administered in the two groups. Image quality was significantly better in the CO 2 group compared to the air group at all four different scanning sites ( P  < 0.01). Similarly, CO 2 correlated with less visual artifacts and need of suction ( P  < 0.01). Conclusions Similarly to previous findings with other endoscopic procedures, EUS was associated with improved scores for abdominal discomfort with CO 2 rather than air insufflation. Moreover, overall EUS image quality was improved using CO 2 insufflation. Future studies are warranted to ascertain whether CO 2 insufflation should be regarded as the standard of care for diagnostic EUS.

Trapping tyrosinase key active intermediate under turnover.

This paper shows for the first time that the spectral features of the ternary complex of tyrosinase/O2/phenol, trapped at low temperature using the very slow substrate 3,5-difluorophenol, are those of a mu-eta2:eta2-peroxidodicopper(II) species, and that this remains the only enzyme species under turnover and substrate saturation conditions.

Clinical usefulness of gastric-juice analysis in 2007: the stone that the builders rejected has become the cornerstone.

BACKGROUND: Gastric juice is usually discarded during upper-GI endoscopy. OBJECTIVE: By using a novel device, the Mt 21-42, we evaluated the potential of this important organic fluid in clinical practice, exploring its contribution to the diagnosis of Helicobacter pylori infection and atrophic gastritis of the oxyntic mucosa (AGOM). DESIGN AND PATIENTS: A multicenter study (17,907 patients; 10 endoscopy units) estimated the frequency of diagnosis of AGOM and H pylori infection in routine endoscopic practice. A prospective study (216 patients) at 1 of these units aimed to determine the real prevalence of these conditions and the possible benefits of gastric juice analysis. We considered gastric juice pH and ammonium concentration, endoscopic and histologic features, serologic parameters for atrophy and H pylori, gastric acid secretion, and costs. RESULTS: We found that H pylori infection and, even more markedly, AGOM were greatly underdiagnosed in routine endoscopic practice (20.1% and 0.8% vs 49.1% and 12.5% in the prospective study, respectively), because of the intrinsic limitations of the conventional tests and lack/inappropriateness of biopsy planning. Gastric-juice analysis proved to be a cheap, simple, and effective way to prevent such underdiagnosis and allowed detection of atrophic gastritis and H pylori in 96% and 98% of cases, and saved costs (cost-effectiveness ratio 209 vs 274-5047). CONCLUSIONS: Gastric juice provided a valuable source of clinicopathologic information that, properly analyzed, allowed detection of the main risk factors for gastric cancer (H pylori and atrophic gastritis), overcoming the diagnostic limitations associated with these conditions and also producing time and cost savings.

Mt 21-42: development and validation of an automatic device proposed for the endoscopic diagnosis of Helicobacter pylori infection and atrophic gastritis.

BACKGROUND: Gastric juice may give important clinico-pathological information, but measurements in this medium are difficult. In this study we present and validate an innovative device (Mt 21-42) performing gastric juice analyses during endoscopy and proposed for the endoscopic diagnosis of Helicobacter pylori infection and hypo/achlorhydria. METHODS: Analyses on both aqueous solutions (80 pH buffer + 120 ammonium chloride samples) and human gastric juice were carried out to assess the measuring performance of Mt 21-42 on the ideal and real matrix, respectively. Matrix spike and manipulation tests were also performed to investigate the matrix effect of gastric juice and to evaluate the consequences of its manipulation on the measurements. Furthermore, preliminary clinical tests were performed to evaluate the clinical potentiality of the device. RESULTS: Mt 21-42 showed a good measuring performance on ideal matrix (coefficient variation: pH = 1.3%, ammonium = 2.1%) and real matrix (coefficient variation: pH = 1.2%, ammonium = 1.9%). Analyses on gastric juice excluded a substantial matrix effect (percent recovery =96.5-98.7%) but demonstrated a significant influence of manipulation procedures (p < 0.05). CONCLUSIONS: Human gastric juice does not have a substantial matrix effect for pH and ammonium determination, but its manipulation may affect the measurement of these components. Mt 21-42 represents a precise instrument for the measurement of gastric juice and a potential precious tool for the endoscopic detection of H. pylori infection and hypo/achlorhydric conditions.