Evaluation of Drug Interactions in Patients Treated with DAAs for Hepatitis C Therapy with Comorbidities and Cardiovascular Issues—A Delphi Consensus Project

Orally administered direct-acting antivirals (DAAs) have dramatically changed the possibility of curing HCV (hepatitis C virus) infection, with the two principal HCV regimens based on the combination of glecaprevir + pibrentasvir (GLE-PIB) and sofosbuvir + velpatasvir (SOF-VEL). A combination of drugs containing NS3/4A protease inhibitors, as well as the fact that almost all HCV patients can be treated at present, may expose patients to a higher rate of drug–drug interactions (DDIs). The hepatitis C treatment recommendations from the EASL (European Association for the Study of the Liver) state that, prior to starting treatment with a DAA, a detailed drug history should be taken; yet, the decision on managing the potential DDIs is not always clear. For this reason, a group of Italian cardiologists and hepatologists promoted a survey among colleagues to assess the controversial issues when treating patients with chronic hepatitis C taking concomitant cardiovascular drugs, aiming to reach a consensus on the best practice to apply when treating a patient with chronic hepatitis C who is taking concomitant drugs for cardiovascular diseases. Two consecutive questionnaires were proposed between June and July 2022 to a qualitative Expert Panel (EP) of 14 gastroenterologists, infectologists, hepatologists, and internists, with statistical analyses performed on 100% of the responses for both questionnaires. Agreement among experts was assessed following the Delphi method as developed by the RAND Corporation. The interviewed experts consider DDIs a critical clinical problem to be evaluated in HCV patients. Therefore, dose changes, drug substitution, and discontinuation of concomitant cardiovascular drugs should be discouraged, even if planned for a relatively short period. Since oral DAAs have different DDIs profiles, hepatologists should prefer the antiviral DAA combination presenting the lowest instance of potential interactions

Tensile strengths of flocculated compacted unsaturated soils

Flocculating agents can be introduced to soils through a number of natural or anthropogenic processes. This paper investigates the effect of flocculant addition (aqueous calcium chloride (CaCl2)) on the tensile strengths of two soils of differing flocculation susceptibility. Tensile strengths were found using the Brazilian (direct splitting) test for a range of suction values. A decrease in tensile strength was found for a soil with high clay content, which was consistent with previous findings in the literature. However, the strength of the soil with lower clay content unexpectedly increased. Results were interpreted using the extended Mohr–Coulomb (EMC) yield criterion fitted to data above the residual suction value. Changes in EMC parameters were used to infer changes in material behaviour on calcium chloride addition. Results have important implications for the design of geotechnical structures, for example engineered cover systems, exposed to flocculating conditions. </jats:p

Analysis of Metal-Insulator Crossover in Strained {SrRuO}3 Thin Films by X-ray Photoelectron Spectroscopy

The electronic properties of ultrathin epitaxial films of strontium ruthenate SrRuO3 perovskite oxide are modified by epitaxial strain, as determined by growing by pulsed laser deposition, on different the substrates. Electron transport measurements indicated that tensile strain deformation of the SrRuO3 unit cell reduces the metallicity of the material and reduces the metal-insulator-transition (MIT) temperatures. The shrinkage of the Ru-O-Ru buckling angle due to compressive strain is counterweighted by the increased overlap of the conduction Ru-4d orbitals with the O-2p ones due to the smaller interatomic distances resulting into an increased MIT temperature, i.e. a more conducting material. In the more metallic samples the core level x-ray photoemission spectroscopy lineshapes show the occurrence of an extra-peak at the lower binding energies of the main Ru-3d peaks that is attributed to screening, as observed in volume sensitive photoemission of the unstrained material

Wider implications of video-assisted thoracic surgery versus open approach for lung metastasectomy

Lung metastasectomy is considered a safe and potentially curative procedure despite there is not a strong evidence that metastasectomy prolongs long-term survival in patients with lung metastases. Moreover, the debate is open regarding the best approach for lung metastasectomy, video-assisted thoracic surgery versus open approach. A systematic review of literature to clarify what is the best approach to prolong survival in patients with lung metastases was performed. Our study confirms that overall survival is equivalent for video-assisted thoracic surgery and thoracotomy, therefore the ‘gold standard’ surgical treatment for lung metastases remains a point of debate. The choice of the surgical approach still depends more on the single center or surgeon practice than on strong scientific evidence. A prospective randomized trial could clarify the question

Boceprevir is highly effective in treatment-experienced hepatitis C virus-positive genotype-1 menopausal women

AIM: To investigate the safety/efficacy of Boceprevirbased triple therapy in hepatitis C virus (HCV)-G1 menopausal women who were historic relapsers, partial-responders and null-responders. METHODS: In this single-assignment, unblinded study, we treated fifty-six menopausal women with HCV-G1, 46% F3-F4, and previous PEG-α/RBV failure (7% null, 41% non-responder, and 52% relapser) with 4 wk lead-in with PEG-IFNα2b/RBV followed by PEGIFNα2b/RBV+Boceprevir for 32 wk, with an additional 12 wk of PEG-IFN-α-2b/RBV if patients were HCV-RNA-positive by week 8. In previous null-responders, 44 wk of triple therapy was used. The primary objective of retreatment was to verify whether a sustained virological response (SVR) (HCV RNA undetectable at 24 wk of follow-up) rate of at least 20% could be obtained. The secondary objective was the evaluation of the percent of patients with negative HCV RNA at week 4 (RVR), 8 (RVR BOC), 12 (EVR), or at the end-of-treatment (ETR) that reached SVR. To assess the relationship between SVR and clinical and biochemical parameters, multiple logistic regression analysis was used. RESULTS: After lead-in, only two patients had RVR; HCV-RNA was unchanged in all but 62% who had ≤ 1 logio decrease. After Boceprevir, HCV RNA became undetectable at week 8 in 32/56 (57.1%) and at week 12 in 41/56 (73.2%). Of these, 53.8% and 52.0%, respectively, achieved SVR. Overall, SVR was obtained in 25/56 (44.6%). SVR was achieved in 55% previous relapsers vs. 41% non-responders (Ρ = 0.250), in 44% F0-F2 vs 54% F3-F4 (Ρ = 0.488), and in 11/19 (57.9%) of patients with cirrhosis. At univariate analysis for baseline predictors of SVR, only previous response to antiviral therapy (OR = 2.662, 95%CI: 0.957-6.881, Ρ= 0.043), was related with SVR. When considering "on treatment" factors, 1 log10 HCV RNA decline at week 4 (3.733, 95%CI: 1.676-12.658, Ρ= 0.034) and achievement of RVR BOC (7.347, 95%CI: 2.156-25.035, Ρ= 0.001) were significantly related with the SVR, al-though RVR BOC only (6.794, 95%CI: 1.596-21.644, Ρ = 0.010) maintained significance at multivariate logistic regression analysis. Anemia and neutropenia were managed with Erythropoietin and Filgrastim supplementation, respectively. Only six patients discontinued therapy. CONCLUSION: Boceprevir obtained high SVR response independent of previous response, RVR or baseline fibrosis or cirrhosis. RVR BOC was the only independent predictor of SVR

Outlining multi-purpose forest inventories to assess the ecosystem approach in forestry

A summary and discussion of selected published results on the current and potential role of forest inventories (with particular reference to the national ones) are presented in the light of the challenges posed by society and policy decisions in the environmental sector. The analysis concentrates mainly on the ecological and socio-economic aspects of the question and on forest inventories’ potential contribution to achieving sustainable forest management.L'articolo è diponibile sul sito dell'editore wwww.tandf.co.uk/journals

The hepatitis D virus in Italy. A vanishing infection, not yet a vanished disease

Introduction: Hepatitis D Virus (HDV) infection is vanishing in Italy. It is therefore believed that hepatitis D is no longer a medical problem in the domestic population of the country but remains of concern only in migrants from HDV-endemic areas. Objectives: To report the clinical features and the medical impact of the residual domestic HDV infections in Italy. Methods: From 2010 to 2019, one hundred ninety-three first-time patients with chronic HDV liver disease attended gastroenterology units in Torino and San Giovanni Rotondo (Apulia); 121 were native Italians and 72 were immigrants born abroad. For this study, we considered the 121 native Italians in order to determine their clinical features and the impact of HDV disease in liver transplant programs. Results: At the last observation the median age of the 121 native Italians was 58 years. At the end of the follow-up, the median liver stiffness was 12.0 kPa (95% CI 11.2–17.4), 86 patients (71.1%) had a diagnosis of cirrhosis; 80 patients (66.1%) remained HDV viremic. The ratio of HDV to total HBsAg transplants varied from 38.5% (139/361) in 2000–2009 to 50.2% (130/259) in 2010–2019, indicating a disproportionate role of hepatitis D in liver transplants compared to the minor prevalence of HDV infections in the current scenario of HBsAg-positive liver disorders in Italy. Conclusion: Though HDV is vanishing in Italy, a legacy of ageing native-Italian patients with advanced HDV liver disease still represents an important medical issue and maintains an impact on liver transplantation

Serological Response to BNT162b2 Anti-SARS-CoV-2 Vaccination in Patients with Inflammatory Rheumatic Diseases: Results From the RHEUVAX Cohort

Objective: In the light of the current COVID-19 epidemic and the availability of effective vaccines, this study aims to identify factors associated with non-response to anti-SARS-CoV-2 vaccines as immunological alteration associated with immune rheumatic diseases (IRD) and immunosuppressive medications may impair the response to vaccination. Methods: Volunteers in the health profession community with IRD, age, and sex-matched controls (CTRL) who underwent vaccination with two doses of BNT162b2 were recruited for this study. Anti-Trimeric Spike protein antibodies were assayed eight ± one weeks after the second vaccine dose. Univariate and logistic regression analyses were performed to identify factors independently associated with non-response and low antibody titers. Results: Samples were obtained from 237 IRD patients (m/f 73/164, mean age 57, CI 95% [56-59]): 4 autoinflammatory diseases (AI), 62 connective tissue diseases (CTD), 86 rheumatoid arthritis (RA), 71 spondylarthritis (SpA) and 14 vasculitis (Vsc). 232 CTRL were recruited (m/f 71/161, mean age 57, CI 95% [56-58]). Globally, IRD had a lower seroconversion rate (88.6% vs 99.6%, CI 95% OR [1.61-5.73], p&lt;0.001) and lower antibody titer compared to controls (median (IQR) 403 (131.5-1012) versus 1160 (702.5-1675), p&lt;0.001). After logistic regression, age, corticosteroid (CCS), Abatacept and Mycophenolate Mofetil (MMF) use were associated with non-response. Lower antibody titer was associated with the use of MMF, ABA, CCS, Rituximab, tumor necrosis factor inhibitor, JAK inhibitors, and higher age. Conclusion: The response to anti-SARS-CoV-2 vaccines is often impaired in IRD patients under treatment and may pose them at higher risk of severe COVID-19. Specific vaccination protocols are desirable for these patients