Efficacy and safety of treatment with biologicals (benralizumab,dupilumab, mepolizumab,omalizumab and reslizumab) for severe eosinophilic asthma. A systematic review for the EAACI Guidelines - recommendations on the use of biologicals in severe asthma

Five biologicals have been approved for severe eosinophilic asthma, a well-recognized phenotype. Systematic reviews (SR) evaluated the efficacy and safety of benralizumab, dupilumab, mepolizumab, omalizumab and reslizumab (alphabetical order) compared to standard of care for severe eosinophilic asthma. PubMed, Embase and Cochrane Library were searched to identify RCTs and health economic evaluations, published in English. Critical and important asthma-related outcomes were evaluated for each of the biologicals. The risk of bias and the certainty of the evidence were assessed using GRADE. 19 RCTs (three RCTs for benralizumab, three RCTs for dupilumab, three RCTs for mepolizumab, five RCTs for omalizumab and five RCTs for reslizumab), including subjects 12 to 75 years old (except for omalizumab including also subjects 6-11 years old), ranging from 12 to 56 weeks were evaluated. All biologicals reduce exacerbation rates with high certainty of evidence: benralizumab incidence rate ratio (IRR) 0.53 (95% CI 0.39 to 0.72), dupilumab (IRR) 0.43 (95% CI 0.32 to 0.59), mepolizumab IRR 0.49 (95% CI 0.38 to 0.66), omalizumab (IRR) 0.56 (95% CI 0.40 to 0.77) and reslizumab (IRR) 0.46 (95% CI 0.37 to 0.58). Benralizumab, dupilumab and mepolizumab reduce the daily dose of oral corticosteroids (OCS) with high certainty of evidence. All evaluated biologicals probably improve asthma control, QoL and FEV₁, without reaching the minimal important difference (moderate certainty). Benralizumab, mepolizumab and reslizumab slightly increase drug-related adverse events (AE) and drug-related serious AE (low to very low certainty of evidence). The incremental cost-effectiveness ratio per quality-adjusted life year value is above the willingness to pay threshold for all biologicals (moderate certainty). Potential savings are driven by decrease in hospitalizations, emergency and primary care visits. There is high certainty that all approved biologicals reduce the rate of severe asthma exacerbations and for benralizumab, dupilumab and mepolizumab for reducing OCS. There is moderate certainty for improving asthma control, QoL, FEV₁. More data on long-term safety are needed together with more efficacy data in the paediatric population.     

Influence of Alkali Activator Type on the Hydrolytic Stability and Intumescence of Inorganic Polymers Based on Waste Glass

The main objective of this study is the synthesis and characterization of low cost alkali-activated inorganic polymers based on waste glass (G-AAIPs) using a mixture of NaOH and Ca(OH)₂ as alkali activators, in order to improve their hydrolytic stability. This paper also presents detailed information about the influence of composition determined by X Ray Diffraction (XRD), microstructure determined by Scanning Electronic Microscopy (SEM) and processing parameters on the main properties of G-AAIP pastes. The main factors analyzed were the glass fineness and the composition of the alkaline activators. The influence on intumescent behavior was also studied by heat treating of specimens at 600 °C and 800 °C. The use of Ca(OH)₂ in the composition of the alkaline activator determines the increase of the hydrolytic stability (evaluated by underwater evolution index) of the G-AAIP materials compared to those obtained by NaOH activation. In this case, along with sodium silicate hydrates, calcium silicates hydrates (C-S-H), with good stability in a humid environment, were also formed in the hardened pastes. The highest intumescence and an improvement of hydrolytic stability (evaluated by underwater evolution index and mass loss) was achieved for the waste glass powder activated with a solution containing 70% NaOH and 30% Ca(OH)₂. The increase of the waste glass fineness and initial curing temperature of G-AAIPs have a positive effect on the intumescence of resulted materials but have a reduced influence on their mechanical properties and hydrolytic stability.     

Predictive factors of failure to control bleeding and 6-week mortality after variceal hemorrhage in liver cirrhosis – a tertiary referral center experience

IntroductionMortality from variceal bleeding remains high despite the therapeutic progress in severe cirrhosis. Understanding the predictive factors of failure to control bleeding (FTB) and mortality will lead to better future therapies. Comorbidities are thought to be important prognostic factors for variceal bleeding. The aim of the study was to assess the factors associated with FTB and with 42-day mortality and to evaluate the influence of comorbidities on these patients’ prognosis.Material and methodsWe prospectively included in the study all consecutive patients with cirrhosis and variceal bleeding presenting to the emergency room and we followed them up over 6 weeks. CirCom score and Charlson index were used for the assessment of comorbidities.ResultsOf the 138 patients included in the study, 27 (19.5%) were considered to have FTB. Child C class (74.07% vs. 32.43%, p < 0.001), Meld score (20.5 vs. 16.00, p = 0.004) and creatinine level (1.04 vs. 0.81, p = 0.01) were associated with FTB, but only Child class was independently associated with FTB in multivariate analysis (OR = 2.94, p = 0.006). Mortality at 42 days (21.7%) was influenced by the severity of the disease assessed through Child class (76.66% vs. 30.55% – Child C, p < 0.001) and MELD score (21.00 vs. 16.00, p < 0.001). Creatinine level (1.00 vs. 0.7, p = 0.02) and acute kidney injury (26.66% vs. 7.40%, p = 0.009) were also prognostic factors for the 6-week mortality. Comorbidities did not influence the mortality (CirCom > 1 (16.7% vs. 21.3%, p = 0.76) or Charlson index > 4 (36% vs. 47.2%, p = 0.41).ConclusionsThe severity of cirrhosis is an important prognostic factor for FTB and 42-day mortality. Identifying the factors associated with early mortality may help selecting patients needing more than conventional therapy.     

Compatibility of Drotaverine Hydrochloride with Ibuprofen and Ketoprofen Nonsteroidal Anti-Inflammatory Drugs Mixtures

Formulations with two or more active pharmaceutical ingredients (APIs) are a researched trend due to their convenient use compared with multiple medications. Moreover, drug-drug combinations may have a synergistic effect. Drotaverine hydrochloride (D-HCl) is commonly used for its antispasmodic action. The combination of a spasmolytic and an analgesic drug such as ibuprofen (Ibu) or ketoprofen (Ket) could become the answer for the treatment of localized pain. D-HCl:Ibu and D-HCl:Ket drug-drug interactions leading to the formation of eutectic compositions with increased bioavailability, obtained by mechanosynthesis, a green, solvent-free method was explored for the first time. The compatibility of Ibuprofen, Ketoprofen, and Drotaverine Hydrochloride was investigated using differential scanning calorimetry (DSC), X-ray diffraction (XRD), and Fourier-Transform Infrared spectroscopy (FTIR). Solid-liquid equilibrium (SLE) phase diagrams for the binary systems of active pharmaceutical ingredients were developed and the Tammann diagrams were designed to determine the eutectic compositions. The excess thermodynamic functions G^E for the pre-, post-, and eutectic compositions were obtained using the computed activity coefficients data. Results show that drotaverine-based pharmaceutical forms for pain treatment may be obtained at 0.9 respectively 0.8 molar fractions of ibuprofen and ketoprofen which is advantageous because the maximum allowed daily dose of Ibu is about 6 times higher than those of D-HCl and Ket. The obtained eutectics may be a viable option for the treatment of pain associated with cancer therapy.     

Superior vena cava graft infection in thoracic surgery: a retrospective study of the French EPITHOR database

 Open in a separate windowOBJECTIVESTo report our experience on the management of superior vena cava graft infection.METHODSBetween 2001 and 2018, patients with superior vena cava synthetic graft or patch reconstruction after resection of intrathoracic tumours or benign disease were selected retrospectively from the French EPITHOR database and participating thoracic centres. Our study population includes patients with superior vena cava graft infection, defined according to the MAGIC consensus. Superior vena cava synthetic grafts in an empyema or mediastinitis were considered as infected.RESULTSOf 111 eligible patients, superior vena cava graft infection occurred in 12 (11.9%) patients with a polytetrafluoroethylene graft secondary to contiguous contamination. Management consisted of either conservative treatment with chest tube drainage and antibiotics (n = 3) or a surgical graft-sparing strategy (n = 9). Recurrence of infection appears in 6 patients. Graft removal was performed in 2 patients among the 5 reoperated patients. The operative mortality rate was 25%.CONCLUSIONSSuperior vena cava graft infection may develop as a surgical site infection secondary to early mediastinitis or empyema. Graft removal is not always mandatory but should be considered in late or recurrent graft infection or in infections caused by aggressive microorganisms (virulent or multidrug resistant bacteria or fungi).     

Calcium,Magnesium, and Zinc Supplementation during Pregnancy: The Additive Value of Micronutrients on Maternal Immune Response after SARS-CoV-2 Infection

Magnesium may contribute to the immune response during and after SARS-CoV-2 infection by acting as a cofactor for immunoglobulin production and other processes required for T and B cell activity. Considering magnesium as a recommended dietary supplement during pregnancy and the possible role of magnesium deficiency in COVID-19 and its complications, the current study sought to determine the effect of magnesium and magnesium-containing nutritional supplements on the immune response following SARS-CoV-2 infection in pregnant women, as well as to observe differences in pregnancy outcomes based on the supplements taken during pregnancy. The study followed a cross-sectional design, where patients with a history of SARS-CoV-2 infection during their pregnancy were surveyed for their preferences in nutritional supplementation and their profile compared with existing records from the institutional database. A cohort of 448 pregnant women with COVID-19 during 22 months of the pandemic was assembled, out of which 13.6% took a magnesium-only supplement, and 16.5% supplemented their diet with a combination of calcium, magnesium, and zinc. Around 60% of patients in the no-supplementation group had the SARS-CoV-2 anti-RBD lower than 500 U/mL, compared with 50% in those who took magnesium-based supplements. A quantity of magnesium >450 mg in the taken supplements determined higher levels of antibody titers after COVID-19. Low magnesium dosage (<450 mg) was an independent risk factor for a weak immune response (OR-1.25, p-value = 0.003). The observed findings suggest supplementing the nutritional intake of pregnant women with magnesium-based supplements to determine higher levels of SARS-CoV-2 anti-RBD antibodies, although causality remains unclear.     

Gamma Irradiation and Ag and ZnO Nanoparticles Combined Treatment of Cotton Textile Materials

In this work, cotton textile materials were impregnated by immersion with three different nanocomposites: Ag/chitosan, Ag/polyvinylpyrrolidone, and ZnO/polyvinylpyrrolidone and irradiated with a ⁶⁰Co gamma source. After the nanoparticles impregnation, the cotton materials were irradiated in a dry and wet state at 5 and 20 kGy radiation doses. The following methods were used for the characterization of the obtained cotton materials to reveal the modification of the textile materials: Fourier transform infrared-attenuated total reflection spectroscopy (FTIR-ATR) and thermogravimetry (TG). The obtained materials have good antibacterial properties. The microbiological tests have shown the best material results for the gamma irradition and Ag nanoparticles combined treatment. The objective was to create a more environmentally friendly approach for textile functionalization by eliminating toxic chemicals-based technology and replacing it with the eco-friendlier gamma technology.     

EAACI Biologicals Guidelines—dupilumab for children and adults with moderate-to-severe atopic dermatitis

Atopic dermatitis imposes a significant burden on patients, families and healthcare systems. Management is difficult, due to disease heterogeneity, co-morbidities, complexity in care pathways and differences between national or regional healthcare systems. Better understanding of the mechanisms has enabled a stratified approach to the management of atopic dermatitis, supporting the use of targeted treatments with biologicals. However, there are still many issues that require further clarification. These include the definition of response, strategies to enhance the responder rate, the duration of treatment and its regimen (in the clinic or home-based), its cost-effectiveness and long-term safety. The EAACI Guidelines on the use of dupilumab in atopic dermatitis follow the GRADE approach in formulating recommendations for each outcome and age group. In addition, future approaches and research priorities are discussed.