Human dental pulp stem cells produce mineralized matrix in 2D and 3D cultures

The aim of this study was to characterize the in vitro osteogenic differentiation of dental pulp stem cells (DPSCs) in 2D cultures and 3D biomaterials. DPSCs, separated from dental pulp by enzymatic digestion, and isolated by magnetic cell sorting were differentiated toward osteogenic lineage on 2D surface by using an osteogenic medium. During differentiation process, DPSCs express specific bone proteins like Runx-2, Osx, OPN and OCN with a sequential expression, analogous to those occurring during osteoblast differentiation, and produce extracellular calcium deposits. In order to differentiate cells in a 3D space that mimes the physiological environment, DPSCs were cultured in two distinct bioscaffolds, Matrigel™ and Collagen sponge. With the addition of a third dimension, osteogenic differentiation and mineralized extracellular matrix production significantly improved. In particular, in Matrigel™ DPSCs differentiated with osteoblast/osteocyte characteristics and connected by gap junction, and therefore formed calcified nodules with a 3D intercellular network. Furthermore, DPSCs differentiated in collagen sponge actively secrete human type I collagen micro-fibrils and form calcified matrix containing trabecular-like structures. These neo-formed DPSCs-scaffold devices may be used in regenerative surgical applications in order to resolve pathologies and traumas characterized by critical size bone defects

Human dental pulp stem cells (HDPSC) versus osteoblast-like cells: comparison for capability of adhesion, growth and bone matrix formation on differently-shaped surfaces of biomaterials.

Comparisons between HDPSC and osteoblast-like cells are made in regards to bone matrix production as well as distribution, density and adhesion to the biomaterial surfaces

Bictegravir/Emtricitabine/Tenofovir Alafenamide Treatment: Efficacy and Tolerability in Clinical Practice

Diana Canetti,1 Laura Galli,1 Riccardo Lolatto,1 Silvia Nozza,2 Vincenzo Spagnuolo,1 Camilla Muccini,1 Benedetta Trentacapilli,2 Elena Bruzzesi,2 Martina Ranzenigo,2 Matteo Chiurlo,2 Antonella Castagna,1,2 Nicola Gianotti1 1Infectious Diseases Unit, San Raffaele Scientific Institute, Milan, Italy; 2Infectious Diseases Unit, Vita Salute San Raffaele University, Milan, ItalyCorrespondence: Diana Canetti, Infectious Diseases Unit San Raffaele Scientific Institute, Via Stamira D’Ancona 20, Milano, 20127, Italy, Tel +390226432461, Fax +390226437943, Email [email protected]: Analysis of bictegravir/emtricitabine/tenofovir alafenamide (BFTAF) efficacy and safety in virologically suppressed people living with HIV (PLWH) in clinical practice.Patients and methods: The retrospective cohort study, which included adult treatment-experienced and virologically suppressed PLWH, switched to BFTAF from June 2019 to June 2021. Efficacy and safety were evaluated as virological failure (VF=2 consecutive HIV-RNA> 50 copies/mL or a single HIV-RNA> 400 copies/mL) and treatment failure (TF=VF or discontinuation for any reason) until data freezing (August 2022).Results: Of the 1040 PLWH included, 67.8% switched from elvitegravir/cobicistat/FTAF. VF occurred in 4.2% (n=44), with incidence rate of 1.63 per 1000 person-months of follow-up (PMFU) and probability at 24– 30 months of 3.8%– 4.0%, respectively. Out of the 44 VF, in 75% virological re-suppression was achieved while maintaining BFTAF. Discontinuation occurred in 15% after a median time of 13.5 months of follow-up, with an incidence rate of 5.67 per 1000 PMFU, and a probability at 24– 30 months of 11.9%– 15.3%, respectively. Main discontinuation reasons were simplification (51.3%) and toxicity (21.8%, involving CNS in half of cases). TF occurred in 18.6% with an incidence rate of 7.01 per 1000 PMFU after a median time of 13.6 observation months; probability at 24– 30 months was 14.8%– 18.4%, respectively.Conclusion: BFTAF has proven effective and well tolerated in clinical practice.Plain Language Summary: In Clinical Randomized Trials, BFTAF proved to have a high genetic barrier regimen.In this context of clinical practice:BFTAF proved effective and well toleratedIt showed a low rate of virological failureDiscontinuation was largely influenced by simplification with 2-drug regimens.Keywords: bictegravir, people living with HIV, PLWH, efficacy, safety, clinical practic

Antibiotic appropriateness for Gram-negative bloodstream infections: impact of infectious disease consultation

Background: We investigated the role of infectious disease consultation (IDC) on therapeutic appropriateness in Gram-negative bloodstream infections (GNBSIs) in a setting with a high proportion of antibiotic resistance. Secondary outcomes were in-hospital mortality and the impact of rapid diagnostic tests (RDTs). Methods: Retrospective study on hospitalised patients with GNBSIs. Therapy was deemed appropriate if it had the narrowest spectrum considering infection and patients’ characteristics. Interventional-IDC (I-IDC) group included patients with IDC-advised first appropriate or last non-appropriate therapy. Time to first appropriate therapy and survival were evaluated by Kaplan-Meier curves. Factors associated with therapy appropriateness were assessed by multivariate Cox proportional-hazard models. Results: 471 patients were included. High antibiotic resistance rates were detected: quinolones 45.5%, third-generation cephalosporins 37.4%, carbapenems 7.9%. I-IDC was performed in 31.6% of patients (149/471), RDTs in 70.7% (333/471). The 7-day probability of appropriate treatment was 91.9% (95% confidence interval [95%CI]: 86.4–95.8%) vs. 75.8% (95%CI: 70.9–80.4%) with and without I-IDC, respectively (p-value = 0.0495); 85.5% (95%CI: 81.3–89.1%) vs. 69.4% (95%CI: 61.3–77.2%) with and without RDTs, respectively (p-value = 0.0023). Compared to RDTs alone, the combination with I-IDC was associated with a higher proportion of appropriate therapies at day 7: 81.9% (95%CI: 76.4–86.7%) vs. 92.6% (95%CI: 86.3–96.7%). At multivariate analysis, I-IDC and RDTs were associated with time to first appropriate therapy [adjusted hazard-ratio 1.292 (95%CI: 1.014–1.647) and 1.383 (95%CI: 1.080–1.771), respectively], with no impact on mortality. Conclusions: In a setting with a high proportion of antibiotic resistance, IDC and RDTs were associated with earlier prescription of appropriate therapy in GNBSIs, without impact on mortality