Systemic perfusion at peak incremental exercise in left ventricular assist device recipients: Partitioning pump and native left ventricle relative contribution

AbstractBackgroundIn continuous-flow left ventricular assist device (LVAD) recipients, little is known about the relative pump- and left ventricle-generated blood flow (PBF and LVBF, respectively) contribution to peak systemic perfusion during incremental exercise and about how PBF/LVBF interplay and exercise capacity may be affected by pump speed increase.MethodsTwenty-two LVAD recipients underwent ramp cardiopulmonary exercise tests at fixed and increasing pump speed (+ 1.5% of baseline speed/10 W workload increase), echocardiography and NT-proBNP dosage. Peak systemic perfusion was peak VO2/estimated peak arterio-venous O2 difference, and LVBF was systemic perfusion minus PBF provided by LVAD controller. A change of peak percentage of predicted VO2max (Δpeak%VO2) ≥ 3 in increasing- vs. fixed-speed test was considered significant.ResultsTricuspid annular plane systolic excursion (TAPSE) and NT-proBNP were significantly lower and higher, respectively, in Δpeak%VO2 13 mm as a predictor of Δpeak%VO2 ≥ 3.ConclusionsA significant LVBF contribution to peak systemic perfusion and pump speed increase-induced peak VO2 improvement was detectable only in patients with a more preserved right ventricular systolic function and stable hemodynamic picture. These findings should be taken into consideration when designing LVAD controllers aiming to increase pump speed according to increasing exercise demands

Two Different Therapeutic Approaches for SARS-CoV-2 in hiPSCs-Derived Lung Organoids

The global health emergency for SARS-CoV-2 (COVID-19) created an urgent need to develop new treatments and therapeutic drugs. In this study, we tested, for the first time on human cells, a new tetravalent neutralizing antibody (15033-7) targeting Spike protein and a synthetic peptide homologous to dipeptidyl peptidase-4 (DPP4) receptor on host cells. Both could represent powerful immunotherapeutic candidates for COVID-19 treatment. The infection begins in the proximal airways, namely the alveolar type 2 (AT2) cells of the distal lung, which express both ACE2 and DPP4 receptors. Thus, to evaluate the efficacy of both approaches, we developed three-dimensional (3D) complex lung organoid structures (hLORGs) derived from human-induced pluripotent stem cells (iPSCs) and resembling the in vivo organ. Afterward, hLORGs were infected by different SARS-CoV-2 S pseudovirus variants and treated by the Ab15033-7 or DPP4 peptide. Using both approaches, we observed a significant reduction of viral entry and a modulation of the expression of genes implicated in innate immunity and inflammatory response. These data demonstrate the efficacy of such approaches in strongly reducing the infection efficiency in vitro and, importantly, provide proof-of-principle evidence that hiPSC-derived hLORGs represent an ideal in vitro system for testing both therapeutic and preventive modalities against COVID-19

Blindness and glaucoma: A multicenter data review from 7 academic eye clinics

Purpose To evaluate frequency, conversion rate, and risk factors for blindness in glaucoma patients treated in European Universities. Methods This multicenter retrospective study included 2402 consecutive patients with glaucoma in at least one eye. Medical charts were inspected and patients were divided into those blind and the remainder (''controls''). Blindness was defined as visual acuity-0.05 and/or visual field loss to less than 10°. Results Unilateral and bilateral blindness were respectively 11.0% and 1.6%at the beginning, and 15.5%and 3.6% at the end of the observation period (7.5±5.5 years, range:1-25 years)//conversion to blindness (at least unilateral) was 1.1%/year. 134 eyes (97 patients) developed blindness by POAG during the study. At the first access to study centre, they had mean deviation (MD) of -17.1±8.3 dB and treated intraocular pressure (IOP) of 17.1±6.6 mmHg. During follow-up the IOP decreased by 14%in these eyes but MD deteriorated by 1.1±3.5 dB/year, which was 5-fold higher than controls (0.2±1.6 dB/year). In a multivariate model, the best predictors for blindness by glaucoma were initial MD (p<0.001), initial IOP (p<0.001), older age at the beginning of follow-up (p<0.001), whereas final IOP was found to be protective (p<0.05). Conclusions In this series of patients, blindness occurred in about 20%. Blindness by glaucoma had 2 characteristics: late diagnosis and/or late referral, and progression of the disease despite in most cases IOP was within the range of normality and target IOP was achieved//it could be predicted by high initial MD, high initial IOP, and old age

VAD infections: the lead, the graft and the pump

Ventricular assist device (VAD) implantation has become an established treatment in the case of end-stage heart failure. One of the most important limitations is represented by the need of an extra-corporeal power supply and controller connected to the pump through a percutaneous cable. This may lead to local or even systemic infections that can jeopardize post-operative results. In the case of cable infections, medical treatment is usually less effective because of the presence of biofilms reduces the probability of complete pathogen eradication with specific antibiotic therapy (1). Nowadays ultrasound (US) imaging and computed tomography (CT) are recognized to be the best diagnostic tools to detect and define VAD specific infections. These diagnostic tools allow to identify the presence of infective effusions around the implante

Synthetic Methodologies and Therapeutic Potential of Indole-3-Carbinol (I3C) and Its Derivatives

Indole-3-carbinol (I3C) is a natural product contained in vegetables belonging to the Brassicaceae family and has been studied in recent decades for its biological and pharmacological properties. Herein, we will analyze: (1) the biosynthetic processes and synthetic procedures through which I3C and its main derivatives have been obtained; (2) the characteristics that lead to believe that both I3C and its derivatives are responsible for several important activities&mdash;in particular, antitumor and antiviral, through insights concerning in vitro assays and in vivo tests; (3) the mechanisms of action of the most important compounds considered; (4) the potential social impact that the enhancement of the discussed molecules can have in the prevention and treatment of the pathologies&rsquo; examined field&mdash;first of all, those related to respiratory tract disorders and cancer

Synthetic Methodologies and Therapeutic Potential of Indole-3-Carbinol (I3C) and Its Derivatives

Indole-3-carbinol (I3C) is a natural product contained in vegetables belonging to the Bras- sicaceae family and has been studied in recent decades for its biological and pharmacological prop- erties. Herein, we will analyze: (1) the biosynthetic processes and synthetic procedures through which I3C and its main derivatives have been obtained; (2) the characteristics that lead to believe that both I3C and its derivatives are responsible for several important activities—in particular, an- titumor and antiviral, through insights concerning in vitro assays and in vivo tests; (3) the mecha- nisms of action of the most important compounds considered; (4) the potential social impact that the enhancement of the discussed molecules can have in the prevention and treatment of the pa- thologies’ examined field—first of all, those related to respiratory tract disorders and cancer