Interim 2017/18 influenza seasonal vaccine effectiveness: Combined results from five European studies

Between September 2017 and February 2018, influenza A(H1N1)pdm09, A(H3N2) and B viruses (mainly B/Yamagata, not included in 2017/18 trivalent vaccines) co-circulated in Europe. Interim results from five European studies indicate that, in all age groups, 2017/18 influenza vaccine effectiveness was 25 to 52% against any influenza, 55 to 68% against influenza A(H1N1)pdm09, -42 to 7% against influenza A(H3N2) and 36 to 54% against influenza B. 2017/18 influenza vaccine should be promoted where influenza still circulates

Pharmacokinetics of Direct Oral Anticoagulants in Patients With Atrial Fibrillation and Extreme Obesity

Purpose: Direct oral anticoagulants (DOACs) are recommended in preference to vitamin K antagonists (VKAs) for stroke prevention in patients with atrial fibrillation (AF) eligible for oral anticoagulation therapy; however, data and clinical experiences supporting the use of DOACs in patients with a body mass index ≥40 kg/m2 or weight >120 kg remain limited. The aim of this study was to evaluate the pharmacokinetic properties of DOACs in patients with AF and extreme obesity. Methods: We enrolled all consecutive patients with AF and extreme obesity undergoing treatment with DOACs followed up at Monaldi Hospital, Naples, Italy. To determine peak plasma and trough levels of DOACs, plasma samples were collected at 2nd, 4th, 6th, and 12th hours from the last dose intake in patients receiving apixaban and dabigatran and at the 2nd, 4th, 6th, and 24th hours in those receiving edoxaban and rivaroxaban. The DOACs’ peak and trough plasma levels obtained from our study population were compared with those sourced from pharmacokinetic studies among patients without obesity, defined as a normal reference range in the literature. If at least 1 peak or trough plasma level was found ​​below or above the normal reference ranges, the patients were classified as having out-of-range DOAC plasma levels. Study population was then divided into in-range and out-of-range groups. Baseline characteristics, including DOAC treatment, were compared between the 2 groups. Univariate and multivariate logistic regression analysis were performed to identify baseline variables associated with DOACs’ plasma concentration out of the expected range. Findings: A total of 58 patients (mean [SD] age, 70.93 [8.73] years; 40% female) with extreme obesity (mean [SD] body mass index. 44.43 [3.54] kg/m2) and AF while undergoing DOAC treatment were included in the present study. In 9 patients (15.5 %), the DOAC plasma concentrations were out of the expected ranges (out-of-range group);, indicating a greater likelihood of edoxaban 30 mg treatment (33% vs 2%; P < 0.01) and inappropriate DOAC underdosing (56% vs 4%; P < 0.005) compared with the in-range group. According to the multivariate logistic analysis (P = 0.0011), the inappropriate DOAC underdosing (hazard ratio = 29.37; P = 0.0002) was an independent predictor of DOAC plasma levels out of the expected ranges. Implications: Patients with extreme obesity and AF who were receiving DOAC therapy had DOAC plasma concentrations in the expected range. The inappropriate DOAC underdosing seems to be the only independent clinical factor associated with a plasma concentration of the drug out of the expected range

Clinical outcome prediction in COVID-19 patients by lymphocyte subsets analysis and monocytes’ iTNF-α expression

In December 2019, a novel coronavirus, “SARS-CoV-2”, was recognized as the cause of coronavirus disease 2019 (COVID-19). Several studies have explored the changes and the role of inflammatory cells and cytokines in the immunopathogenesis of the disease, but until today, the results have been controversial. Based on these premises, we conducted a retrospective assessment of monocyte intracellular TNF-α expression (iTNF-α) and on the frequencies of lymphocyte sub-populations in twenty-five patients with moderate/severe COVID-19. We found lymphopenia in all COVID-19 infected subjects compared to healthy subjects. On initial observation, in patients with favorable outcomes, we detected a high absolute eosinophil count and a high CD4+/CD8+ T lymphocytes ratio, while in the Exitus Group, we observed high neutrophil and CD8+ T lymphocyte counts. During infection, in patients with favorable outcomes, we observed a rise in the lymphocyte count, in the monocyte and in Treg lymphocyte counts, and in the CD4+ and in CD8+ T lymphocytes count but a reduction in the CD4+/CD8+ T lymphocyte ratio. Instead, in the Exitus Group, we observed a reduction in the Treg lymphocyte counts and a decrease in iTNF-α expression. Our preliminary findings point to a modulation of the different cellular mediators of the immune system, which probably play a key role in the outcomes of COVID-19

Apixaban in a morbid obese patient with atrial fibrillation: A clinical experience using the plasmatic drug evaluation

We present the case of a 45-year-old man with atrial fibrillation and morbid obesity (weight 128 kg, height 168 cm, BMI 45.4) who was switched from Warfarin 5 mg once daily to Apixaban 5 mg twice daily because he did not achieve at least 60% of the time in therapeutic range. We performed serial determinations of apixaban plasma concentration (at 2, 6, 12, 24 hrs after intake) showing drug levels within reference range, even when the patient lose weight

Evolution of ct findings and lung residue in patients with covid-19 pneumonia: Quantitative analysis of the disease with a computer automatic tool

Purpose: The purpose of this study was to assess the evolution of computed tomography (CT) findings and lung residue in patients with COVID-19 pneumonia, via quantified evaluation of the disease, using a computer aided tool. Materials and methods: We retrospectively evaluated 341 CT examinations of 140 patients (68 years of median age) infected with COVID-19 (confirmed by real-time reverse transcriptase polymerase chain reaction (RT-PCR)), who were hospitalized, and who received clinical and CT examinations. All CTs were evaluated by two expert radiologists, in consensus, at the same reading session, using a computer-aided tool for quantification of the pulmonary disease. The parameters obtained using the computer tool included the healthy residual parenchyma, ground glass opacity, consolidation, and total lung volume. Results: Statistically significant differences (p value ≤ 0.05) were found among quantified volumes of healthy residual parenchyma, ground glass opacity (GGO), consolidation, and total lung volume, considering different clinical conditions (stable, improved, and worsened). Statistically significant differences were found among quantified volumes for healthy residual parenchyma, GGO, and consolidation (p value ≤ 0.05) between dead patients and discharged patients. CT was not performed on cadavers; the death was an outcome, which was retrospectively included to differentiate findings of patients who survived vs. patients who died during hospitalization. Among discharged patients, complete disease resolutions on CT scans were observed in 62/129 patients with lung disease involvement ≤5%; lung disease involvement from 5% to 15% was found in 40/129 patients, while 27/129 patients had lung disease involvement between 16 and 30%. Moreover, 8-21 days (after hospital admission) was an ‘advanced period’ with the most severe lung disease involvement. After the extent of involvement started to decrease-particularly after 21 days-the absorption was more obvious. Conclusions: A complete disease resolution on chest CT scans was observed in 48.1% of discharged patients using a computer-aided tool to quantify the GGO and consolidation volumes; after 16 days of hospital admission, the abnormalities identified by chest CT began to improve; in particular, the absorption was more obvious after 21 days

Naïve/Effector CD4 T cell ratio as a useful predictive marker of immune reconstitution in late presenter HIV patients: A multicenter study

A significant proportion of HIV-infected patients experiencing a late diagnosis highlights the need to define immunological protocols able to help the clinicians in identifying patients at higher risk for immunological failure. The aim of the study was to evaluate the feasibility of easy cytometric tests in defining the effect of antiretroviral treatment (cART) on immunological homeostasis and in identifying predictive markers of early immune recovery. Chronic HIV infected patients (n = 202) were enrolled in a prospective multicentric study, and their immunological profile was studied before (w0) and after 24 weeks (w24) of antiretroviral treatment (cART) using a standardized flow cytometric panel. Based on CD4 T cell count before treatment, patients were divided in late (LP: CD4 <350/mmc), intermediate (IP: 350/mmc<500/mmc) and early (EP: CD4 >500/mmc) presenters. In all groups, cART introduction increased CD4 and CD4/CD8 T cell ratio, naïve T cell (CD4 and CD8) and CD127-expressing CD4 T cells. In parallel, cART significantly reduced effector memory T cells (CD4 and CD8) and T cell activation (CD38+CD8 and CD95+CD4 T cells). Moreover, the frequency of Naïve and Effector CD4 T cells before treatment correlated with several immune parameters key associated with the pathogenesis of HIV, thus mirroring the health of immune system. Interestingly, we identified the Naïve/Effector CD4 T cell ratio (N/EM) at w0 as a marker able to predict early immune recovery. Specifically, in LP, N/EM ratio was significantly higher in immunological responder patients (CD4>500/mmc at w24) when compared to immunological non responder (CD4 T cells <500/mmc at w24). Finally, a multivariate analysis indicates that after 24w patients with N/EM ratio higher than 1.86 at w0 recovered 96 CD4 T cells more than those with N/EM ratio lower than 0.46. Altogether, our data define an easy protocol able to define reliable immunological markers useful for the characterization of immune profile in viremic HIV patients and identify the naïve/effector CD4 T cell ratio as a new tool able to predict an early immune reconstitution potential