Role of new ultrasound technologies in the assessment of portal hypertension in patients with chronic liver disease

Introduzione – Nei pazienti con epatopatia cronica, l'ipertensione portale rappresenta la causa delle principali complicanze (sanguinamento da varici, ascite, encefalopatia epatica) che, insieme all’epatocarcinoma, costituiscono la causa più importante di ospedalizzazione e mortalità. Le metodiche gold-standard per la valutazione dell’ipertensione portale sono la misurazione del gradiente di pressione venosa epatica (HVPG) mediante cateterismo delle vene sovraepatiche e l’esofagogastroduodenoscopia (EGDS) per la ricerca delle varici gastroesofagee; entrambi sono esami invasivi, complessi e costosi. Obiettivi – Analizzare il ruolo delle nuove tecnologie basate sugli ultrasuoni, in particolare dell’elastografia epatica e splenica, nella valutazione non invasiva dell’ipertensione portale. Pazienti e metodi – Sono stati arruolati 64 pazienti con epatopatia cronica compensata sottoposti a misurazione dell’HVPG e/o EGDS e ad elastografia epatica, ed eventualmente splenica, mediante almeno una metodica tra Fibroscan, Elast-PQ e 2D-SWE Aixplorer, per ciascuna delle quali è stata valutata la correlazione tra i valori di stiffness ed i valori di HVPG e l’accuratezza diagnostica per l’ipertensione portale clinicamente significativa (HVPG ≥ 10 mmHg) e le varici esofagee. Risultati – Per tutte e tre le metodiche è stata evidenziata la presenza di una correlazione tra i valori di stiffness epatica e splenica ed i valori di HVPG ed una buona capacità dell’elastografia epatica di predire la presenza o meno sia dell’ipertensione portale clinicamente significativa che delle varici esofagee, anche se con cut-off diversi a seconda della metodica utilizzata. Per l’elastografia splenica invece solo due metodiche su tre (Fibroscan ed Elast-PQ) hanno mostrato una buona accuratezza diagnostica per l’ipertensione portale clinicamente significativa, mentre nessuna aveva un ruolo di rilievo nella diagnosi delle varici esofagee. Conclusioni – Si conferma il ruolo dell’elastografia epatica nella diagnosi non invasiva dell’ipertensione portale clinicamente significativa e delle varici esofagee, con cut-off diversi a seconda della tecnologia utilizzata. Meno rilevante è risultato, nella nostra casistica, il ruolo dell’elastografia splenica.Introduction – In patients with chronic liver disease, portal hypertension is responsible for the development of complications (variceal bleeding, ascites, hepatic encephalopathy) which represent, together with hepatocellular carcinoma, the main cause of hospitalization and mortality. Gold standard methods for the evaluation of portal hypertension are hepatic venous pressure gradient (HVPG) measurement through hepatic vein catheterization and endoscopy; both are invasive, complex and expensive examinations. Aim – To investigate the role of new ultrasound-based technologies, especially liver and spleen elastography, in the non-invasive evaluation of portal hypertension. Patients and methods – We enrolled 64 patients with compensated chronic liver disease who underwent HVPG measurement and/or endoscopy and liver stiffness measurement (if possible together with spleen stiffness measurement) using at least one technology among Fibroscan, Elast-PQ and 2D-SWE Aixplorer. For each technology, we evaluated the correlation between stiffness measurements and HVPG values and the diagnostic accuracy for clinically significant portal hypertension (HVPG ≥ 10 mmHg) and oesophageal varices. Results – All the technologies showed a correlation between liver and spleen stiffness measurements and HVPG values and a good performance of liver elastography to predict the presence or not of both clinically significant portal hypertension and oesophageal varices, even if the cut-off were different according to the technology used. Regarding spleen elastography, only two out of three technologies showed good diagnostic accuracy for clinically significant portal hypertension, while no one played a considerable role in the diagnosis of oesophageal varices. Conclusions – We confirmed the role of liver elastography in the non-invasive diagnosis of clinically significant portal hypertension and oesophageal varices, with different cut-off according to the technology used. The role of spleen elastography was less notable

2D shear wave liver elastography by aixplorer to detect portal hypertension in cirrhosis: an individual patient data meta-analysis

Background & Aims: Liver stiffness measured with 2-dimensional shear wave elas- tography by Supersonic Imagine (2DSWE-SSI) is well-established for fibrosis diagnos- tics, but non-conclusive for portal hypertension. Methods: We performed an individual patient data meta-analysis of 2DSWE-SSI to identify clinically significant portal hypertension (CSPH), severe portal hyperten- sion and large varices in cirrhosis patients, using hepatic venous pressure gradient and upper endoscopy as reference. We used meta-analytical integration of diagnos- tic accuracies with optimized rule-out (sensitivity-90%) and rule-in (specificity-90%) cut-offs. Results: Five studies from seven centres shared data on 519 patients. After exclu- sion, we included 328 patients. Eighty-nine (27%) were compensated and 286 (87%) had CSPH. 2DSWE-SSI < 14 kPa ruled out CSPH with a summary AUROC (sROC), sensitivity and specificity of 0.88, 91% and 37%, and correctly classified 85% of pa- tients, with minimal between-study heterogeneity. The false negative rate was 60%, of which decompensated patients accounted for 78%. 2DSWE-SSI ≥ 32 kPa ruled in CSPH with sROC, sensitivity, specificity and correct classifications of 0.83, 47%, 89% and 55%. In a subgroup analysis, the 14 kPa cut-off showed consistent sensitivity and higher specificity for patients with compensated cirrhosis, without ascites, viral 2 aetiology or BMI < 25 kg/m . 2DSWE-SSI ruled out severe portal hypertension and large varices with fewer correctly classified and lower sROC, and with minimal benefit for ruling in. Conclusion: Liver stiffness using 2-dimensional shear wave elastography below 14 kPa may be used to rule out clinically significant portal hypertension in cirrhosis patients, but this would need validation in populations of compensated liver disease. 2DSWE-SSI cannot predict varices needing treatment

Efficacy and safety of reparixin in patients with severe covid-19 Pneumonia. A phase 3, randomized, double-blind placebo-controlled study

Introduction: Polymorphonuclear cell influx into the interstitial and bronchoalveolar spaces is a cardinal feature of severe coronavirus disease 2019 (COVID-19), principally mediated by interleukin-8 (IL-8). We sought to determine whether reparixin, a novel IL-8 pathway inhibitor, could reduce disease progression in patients hospitalized with severe COVID-19 pneumonia. Methods: In this Phase 3, randomized, double-blind, placebo-controlled, multicenter study, hospitalized adult patients with severe COVID-19 pneumonia were randomized 2:1 to receive oral reparixin 1200&nbsp;mg three times daily or placebo for up to 21&nbsp;days or until hospital discharge. The primary endpoint was the proportion of patients alive and free of respiratory failure at Day 28, with key secondary endpoints being the proportion of patients free of respiratory failure at Day 60, incidence of intensive care unit (ICU) admission by Day 28 and time to recovery by Day 28. Results: Of 279 patients randomized, 182 received at least one dose of reparixin and 88 received placebo. The proportion of patients alive and free of respiratory failure at Day 28 was similar in the two groups {83.5% versus 80.7%; odds ratio 1.63 [95% confidence interval (CI) 0.75, 3.51]; p = 0.216}. There were no statistically significant differences in the key secondary endpoints, but a numerically higher proportion of patients in the reparixin group were alive and free of respiratory failure at Day 60 (88.7% versus 84.6%; p = 0.195), fewer required ICU admissions by Day 28 (15.8% versus 21.7%; p = 0.168), and a higher proportion recovered by Day 28 compared with placebo (81.6% versus 74.9%; p = 0.167). Fewer patients experienced adverse events with reparixin than placebo (45.6% versus 54.5%), most mild or moderate intensity and not related to study treatment. Conclusions: This trial did not meet the primary efficacy endpoints, yet reparixin showed a trend toward limiting disease progression as an add-on therapy in COVID-19 severe pneumonia and was well tolerated. Trial registration: ClinicalTrials.gov: NCT04878055, EudraCT: 2020-005919-51

Bidimensional shear wave ultrasound elastography with supersonic imaging to predict presence of oesophageal varices in cirrhosis

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Imaging Diagnosis of Hepatocellular Carcinoma: Recent Advances of Contrast-Enhanced Ultrasonography with SonoVue

Due to the ability to detect the typical contrast-imaging pattern for hepatocellular carcinoma (HCC), that is hyperenhancement in the arterial phase and hypoenhancement in the late phase on a cirrhotic background, contrast-enhanced ultrasonography (CEUS) was included in the American diagnostic algorithm for HCC in 2005. However, its role has been questioned because of the possibility of misdiagnosis of cholangiocarcinoma. The present review aims to describe the advantages and disadvantages of CEUS applications using Sonovue (R) for HCC. In particular there is focus on the accuracy of CEUS in detecting the typical HCC pattern, the CEUS patterns of intrahepatic cholangiocarcinoma (ICC), the risk of misdiagnosis with HCC, the diagnostic use of CEUS in cases of locoregional and systemic treatments, and the evaluation of response to antiangiogenic treatment using dedicated software

Gasification biochar amendment effects on O. basilicum growth

In this work, the application of biochar from gasification as soil amendant, is studied. The effect on Ocimum basilicum growth with three different substrates was investigated: standard soil as the control sample, soil with 30% wt. of compost added, soil with 30% wt. of biochar added, which biochar was obtained as by-product of a fixed bed gasification process. Five samples for each of the substrates were used in order to increase the statistical validity of the results. 55 days of Ocimum basilicum growth showed that the biochar contributed to an acceleration of the growth and increased the fresh and dry weights with about 50%. In addition, plant height and essential oil content was higher with biochar-based substrates. This application can lead to more efficient and sustainable agricultural processes, giving new impulse to bio-energy production and recycling of by-products in a circular economy context

Gasification of cotton crop residues for combined power and biochar production in Mozambique

Cotton agricultural industry is an important sector for some developing countries, whose energy consumption is dramatically rising. Here, biomass is the most important source of energy, but they are used in an inefficient way, causing atmospheric pollution and wasting resources. Combined energy generation and biochar production using cotton residues briquettes as fuel in a PP20 gasifier plant is investigated. The machine has demonstrated similar performances to its “conventional” use: 14% global efficiency and 1.16 kg/kWhelspecific consumption of cotton briquettes are observed. It is calculated that one-hectare field can generate more than 4 MWh and about 130 kg of biochar per year. Biochar represents a valuable by-product; if used as amendment for cotton growth it can improve the soil conditions, both decreasing the need of fertilizers up to 50%. A circular economic model based on cotton waste gasification is proposed. Clean and affordable energy can be produced, in order to promote a sustainable development of rural areas

Overexpression in metastatic breast cancer supports Syndecan-1 as a marker of invasiveness and poor prognosis

Background Metastasis is the main cause of breast cancer (BC) mortality. Increasing evidence points to a role of syndecan-1 (CD138) expression as a prognostic marker involved in BC tissue and leptomeningeal metastasis. Aim of this study was to investigate and compare syndecan-1 tissue expression and localization in primary and secondary BC, focusing on brain metastases. Methods Syndecan-1 expression was determined by immunohistochemistry. Focal vs diffuse (&lt; or &gt; 50% of cancer cells, respectively) pattern of expression, cellular localization (cytoplasm vs membrane) and intensity of immunostaining on neoplastic cells were evaluated. Moreover, the extent and pattern of expression of syndecan-1 were compared between primary tumors and paired metastases and correlated with the tumor intrinsic subtype. Results A total of 23 cases, 10 with paired primary and metastatic tumor and 13 brain metastases, were evaluated. Syndecan-1 was expressed in both primary and metastatic BC. A diffuse cytoplasmic expression was observed in most primary BCs; by contrast, all metastatic lesions showed a membrane pattern of expression, suggesting a shift in cellular localization of syndecan-1 during the metastatic process. Concerning the extent of expression, we observed in metastatic lesions, a trend of association between intrinsic subtypes and extent of positivity. In particular, both BC characterized by overexpression of HER2 and triple-negative tumors were correlated with a diffuse pattern of expression with a moderate to strong intensity. Conclusion A diffuse cytoplasmic expression was observed in most primary BCs; by contrast, all metastatic lesions showed a membrane pattern of expression, suggesting a shift in cellular localization of syndecan-1 during the metastatic process