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Furosemide (FUR), an active pharmaceutical ingredient (API) belonging to a group of drugs known as loop diuretics, has widespread use, but, is characterized by a strong instability to light, which causes chemical transformations that could give a yellowing phenomenon and have a significant impact from a health and marketing point of view. Many studies have tried to explain this phenomenon under different experimental conditions, but no detailed explanation of the yellowing phenomenon has been provided. This work, unlike the others, provides an overall view and explanation of the behavior of FUR in relation to the yellowing phenomenon, both in the solution and in solid state, considering several aspects, such as light exposure, presence of oxygen, and moisture effects.

Most tablets put on the market are coated with polymers soluble in water. The Opadry II 85 series from Colorcon Inc., is a family of PVA-based products marketed since the 1990s. Despite numerous publications on the properties of PVA, to date, limited work has been undertaken to determine the physico-chemical parameters (i.e., UV light, high temperature, and relative humidity) that could affect the performance of PVA-based coatings. To this end, we performed artificial ageing processes on samples made of Opadry Orange II or of some selected components of this coating and analysed them by means of a multidisciplinary approach, using, for example, FTIR, NMR, rheology, and DMTA measurements. In this way, we analysed the influence of the critical components of the Opadry Orange II formula, such as titanium dioxide and aluminium hydroxide, on the coating characteristics under ageing conditions.

Aims Myocardial injury (MI) in coronavirus disease‐19 (COVID‐19) is quite prevalent at admission and affects prognosis. Little is known about troponin trajectories and their prognostic role. We aimed to describe the early in‐hospital evolution of MI and its prognostic impact. Methods and results We performed an analysis from an Italian multicentre study enrolling COVID‐19 patients, hospitalized from 1 March to 9 April 2020. MI was defined as increased troponin level. The first troponin was tested within 24 h from admission, the second one between 24 and 48 h. Elevated troponin was defined as values above the 99th percentile of normal values. Patients were divided in four groups: normal, normal then elevated, elevated then normal, and elevated. The outcome was in‐hospital death. The study population included 197 patients; 41% had normal troponin at both evaluations, 44% had elevated troponin at both assessments, 8% had normal then elevated troponin, and 7% had elevated then normal troponin. During hospitalization, 49 (25%) patients died. Patients with incident MI, with persistent MI, and with MI only at admission had a higher risk of death compared with those with normal troponin at both evaluations (P < 0.001). At multivariable analysis, patients with normal troponin at admission and MI injury on Day 2 had the highest mortality risk (hazard ratio 3.78, 95% confidence interval 1.10–13.09, P = 0.035). Conclusions In patients admitted for COVID‐19, re‐test MI on Day 2 provides a prognostic value. A non‐negligible proportion of patients with incident MI on Day 2 is identified at high risk of death only by the second measurement.

BackgroundPulmonary embolism (PE) has been described in coronavirus disease 2019 (COVID-19) critically ill patients, but the evidence from more heterogeneous cohorts is limited.MethodsData were retrospectively obtained from consecutive COVID-19 patients admitted to 13 Cardiology Units in Italy, from March 1st to April 9th, 2020, and followed until in-hospital death, discharge, or April 23rd, 2020. The association of baseline variables with computed tomography-confirmed PE was investigated by Cox hazards regression analysis. The relationship between d-dimer levels and PE incidence was evaluated using restricted cubic splines models.ResultsThe study included 689 patients (67.3 ± 13.2 year-old, 69.4% males), of whom 43.6% were non-invasively ventilated and 15.8% invasively. 52 (7.5%) had PE over 15 (9–24) days of follow-up. Compared with those without PE, these subjects had younger age, higher BMI, less often heart failure and chronic kidney disease, more severe cardio-pulmonary involvement, and higher admission d-dimer [4344 (1099–15,118) vs. 818.5 (417–1460) ng/mL, p < 0.001]. They also received more frequently darunavir/ritonavir, tocilizumab and ventilation support. Furthermore, they faced more bleeding episodes requiring transfusion (15.6% vs. 5.1%, p < 0.001) and non-significantly higher in-hospital mortality (34.6% vs. 22.9%, p = 0.06). In multivariate regression, only d-dimer was associated with PE (HR 1.72, 95% CI 1.13–2.62; p = 0.01). The relation between d-dimer concentrations and PE incidence was linear, without inflection point. Only two subjects had a baseline d-dimer < 500 ng/mL.ConclusionsPE occurs in a sizable proportion of hospitalized COVID-19 patients. The implications of bleeding events and the role of d-dimer in this population need to be clarified.Graphic abstract

Abstract To compare the efficacy and safety of different mechanical circulatory support (MCS) devices in CS. A total of 24 studies (7 randomized controlled trials—RCTs—and 17 non-RCTs) involving 11,117 patients were entered in a Bayesian network meta-analysis. The primary endpoint was 30-day mortality. Secondary endpoints were stroke and bleeding (requiring transfusion and/or intracranial and/or fatal). Compared with no MCS, extra-corporeal membrane oxygenation (ECMO) reduced 30-day mortality when used both alone (OR 0.37, 95% CrI 0.15–0.90) and together with the micro-axial pump Impella (OR 0.13, 95% CrI 0.02–0.80) or intra-aortic balloon pump (IABP) (OR 0.19, 95% CrI 0.05–0.63), although the relevant articles were affected by significant publication bias. Consistent results were obtained in a sensitivity analysis including only studies of CS due to myocardial infarction. After halving the weight of studies with a non-RCT design, only the benefit of ECMO + IABP on 30-day mortality was maintained (OR 0.22, 95% CI 0.057–0.76). The risk of bleeding was increased by TandemHeart (OR 13, 95% CrI 3.50–59), Impella (OR 5, 95% CrI 1.60–18), and IABP (OR 2.2, 95% CrI 1.10–4.4). No significant differences were found across MCS strategies regarding stroke. Although limited by important quality issues, the studies performed so far indicate that ECMO, especially if combined with Impella or IABP, reduces short-term mortality in CS. MCS increases the hazard of bleeding.

Data concerning the combined prognostic role of natriuretic peptide (NP) and troponin in patients with COVID-19 are lacking. The aim of the study is to evaluate the combined prognostic value of NPs and troponin in hospitalized COVID-19 patients. From March 1, 2020 to April 9, 2020, consecutive patients with COVID-19 and available data on cardiac biomarkers at admission were recruited. Patients admitted for acute coronary syndrome were excluded. Troponin levels were defined as elevated when greater than the 99th percentile of normal values. NPs were considered elevated if above the limit for ruling in acute heart failure (HF). A total of 341 patients were included in this study, mean age 68 ± 13 years, 72% were men. During a median follow-up period of 14 days, 81 patients (24%) died. In the Cox regression analysis, patients with elevated both NPs and troponin levels had higher risk of death compared with those with normal levels of both (hazard ratio 2.94; 95% confidence interval 1.31 to 6.64; p = 0.009), and this remained significant after adjustment for age, gender, oxygen saturation, HF history, and chronic kidney disease. Interestingly, NPs provided risk stratification also in patients with normal troponin values (hazard ratio 2.86; 95% confidence interval 1.21 to 6.72; p = 0.016 with high NPs levels). These data show the combined prognostic role of troponin and NPs in COVID-19 patients. NPs value may be helpful in identifying patients with a worse prognosis among those with normal troponin values. Further, NPs’ cut-point used for diagnosis of acute HF has a predictive role in patients with COVID-19.

Abstract Aims To compare the safety and efficacy of very short (≤3 months), short (6 months), standard (12 months), and extended (>12 months) dual antiplatelet therapy (DAPT), and of subsequent monotherapies, after coronary drug-eluting stent (DES) implantation. Methods and results Twenty-two randomized control trials (n = 110 059 patients/year) were selected and included in a Bayesian network meta-analysis. The primary efficacy endpoint (PEP) was a composite of cardiac death, myocardial infarction (MI), and stent thrombosis (ST), with each of the components of the PEP being a secondary efficacy endpoint. The primary safety endpoint was major bleeding rate. Compared to standard, we found a lower rate of MI [odds ratio (OR) 0.56, 95% confidence interval (CI) 0.44–0.77] in extended, a lower rate of major bleeding (OR 0.61, 95% CI 0.39–0.87) in very short, and a lower rate of any bleeding (OR 0.61, 95% CI 0.38–0.90) in short DAPT. All DAPT durations were comparable regarding the secondary efficacy endpoints. Very short DAPT followed by P2Y12 inhibition was the treatment of choice to reduce both major bleeding and MI. In the ACS subgroup, extended DAPT (as compared to standard) reduced PEP and ST rates (but not MIs). Conclusion The efficacy of short and very short is comparable with that of standard DAPT after DES implantation, whereas extended DAPT reduces MI rate. Very short DAPT is associated with lower haemorrhagic events and, followed by a P2Y12 inhibitor monotherapy, should be preferred in order to pursue a trade-off between major bleeding and ischaemic events.

This study shows that Escherichia coli can be temporarily enriched in zooplankton in natural conditions and that these bacteria can belong to different phylogroups and sequence types including environmental as well as clinical and animal isolates. We isolated 10 E. coli strains and sequenced the genomes of two of them. Phylogenetically the two isolates were closer to strains isolated from poultry meat than with freshwater E. coli, albeit their genomes were smaller than those from poultry. After isolation and fluorescent protein tagging of strains ED1 and ED157 we show that Daphnia sp. can take up these strains and release them alive again, thus forming a temporary host for E. coli. In a chemostat experiment we show that the association does not prolong the bacterial long-term survival, but that at low abundances it does also not significantly reduce the bacterial numbers. We demonstrate that E. coli does not belong to the core microbiota of Daphnia, suffers from competition by the natural microbiota of Daphnia, but can profit from its carapax to survive in water. All in all, this study suggests that the association of E. coli to Daphnia is only temporary but that the cells are viable therein and this might allow encounters with other bacteria for genetic exchange and potential genomic adaptations to the freshwater environment. The contamination of freshwaters with faecal derived bacteria is of major concern regarding drinking water acquisition and recreational activities. Ecological interactions promoting their persistence are still very scarcely studied. This study, which analyses the survival of E. coli in the presence of zooplankton, is thus of ecological as well as water safety relevance.

The relationships between problematic smartphone use and psychological factors have been extensively investigated. However, previous studies generally used variable-centered approaches, which hinder an examination of the heterogeneity of smartphone impact on everyday life. In the present study, we capitalized on latent profile analysis to identify various classes of smartphone owners based on the impact associated with smartphone use (e.g., unregulated usage, preference for smartphone-mediated social relationships) and to compare these classes in terms of established psychological risk factors for problematic smartphone use. We surveyed 934 young adults with validated psychometric questionnaires to assess the impact of smartphones, psychopathological symptoms, self-esteem and impulsivity traits. Smartphone users fall into four latent profiles: users with low smartphone impact, users with average smartphone impact, problematic smartphone users, and users favoring online interactions. Individuals distributed in the problematic smartphone user profile were characterized by heightened psychopathological symptoms (stress, anxiety, depression, obsessive-compulsive tendencies) and impulsivity traits. Moreover, users who preferred online interactions exhibited the highest symptoms of social anxiety and the lowest levels of self-esteem. These findings further demonstrate the multidimensionality and heterogeneity of the impact of smartphone use, calling for tailored prevention and intervention strategies. •Latent profile analysis was used to identify four profiles of smartphone users.•Problematic users are characterized by psychopathological symptoms and impulsivity.•Users favoring online interactions present social anxiety and low self-esteem.

The aim of the present study was to test an explanatory model for individual and social wellbeing which incorporates the advantages of using digital technologies during the COVID-19 pandemic. The study was carried out in Italy, one of the countries that has been most severely affected by the pandemic worldwide. The study was designed to include variables that might be specifically pertinent to the uniqueness of the restrictions imposed by the pandemic. Adults living in Italy (n = 1412) completed an online survey during the lockdown period in March 2020. Results showed two distinct digital interaction processes highlighted by the facilitating use of online emotions (“e-motions”) and online social support (“e-support”). In short, e-motions were positively related to posttraumatic growth, which in turn was positively associated with positive mental health and higher engagement in prosocial behaviors. Moreover, individuals who perceived themselves as having greater e-support were characterized by higher levels of positive mental health, which it turn was positively associated with prosocial behaviors. Collectively, these two digital interaction processes suggest that digital technologies appear to be critical resources in helping individuals cope with difficulties raised by the COVID-19 pandemic.