Germany’s next shutdown—Possible scenarios and outcomes

With the rapid increase of reported COVID‐19 cases, German policymakers announced a 4‐week “shutdown light” starting on November 2, 2020. Applying mathematical models, possible scenarios for the evolution of the outbreak in Germany are simulated. The results indicate that independent of the effectiveness of the current restrictive measures they might not be sufficient to mitigate the outbreak. Repeated shutdown periods or permanently applied measures over the winter could be successful alternatives.     

Peri-implant bone tissues around retrieved human implants after time periods longer than 5 years: a retrospective histologic and histomorphometric evaluation of 8 cases

Only rarely, it is possible to find in the literature histological reports of human retrieved implants, especially after several years of functional loading. These implants can help us in understanding the reactions of peri-implant bone. The aim of this study was to perform a histologic and histomorphometric analysis of the peri-implant tissues behavior and of the bone–titanium interface in titanium dental implants retrieved from patients after time periods longer than 5 years. The archives of the Implant Retrieval Center of the Dental School of the University of Chieti-Pescara, Italy were searched for human dental implants, retrieved after a loading period of more than 5 years. A total of 8 implants were found: 3 of these had been retrieved after 5 years, 1 after 6 years, one after 10 years, 1 after 14 years, 1 after 18 years, 1 after 22 years. Only the bone to implant contact in the three best threads was evaluated. Compact, mature, lamellar bone, with few and small marrow spaces, was present around the implants. Osteons with Haversian canals were present inside some threads, in close proximity to the interface, at both cortical and trabecular regions. Other osteons had a direction perpendicular to the direction of the long axis of the implants. Numerous reversal lines were present. At higher magnification, no gaps or fibrous, connective tissues were present at the interface. The BIC of the three best threads for all implants varied from 94 to 100 %.In conclusion, within the limitations of the present report histology showed that implants with different surfaces all presented the potential to maintain osseointegration over a long period, with a continuous remodeling at the interface, as indicated by the presence of reversal lines.     

Platelet‐rich plasma counteracts detrimental effect of high‐glucose concentrations on mesenchymal stem cells from Bichat fat pad

Diabetic patients display increased risk of periodontitis and failure in bone augmentation procedures. Mesenchymal stem cells (MSCs) and platelet‐rich plasma (PRP) represent a relevant advantage in tissue repair process and regenerative medicine. We isolated MSCs from Bichat's buccal fat pad (BFP) and measured the effects of glucose and PRP on cell number and osteogenic differentiation potential. Cells were cultured in the presence of 5.5‐mM glucose (low glucose [LG]) or 25‐mM glucose (high glucose [HG]). BFP–MSC number was significantly lower when cells were cultured in HG compared with those in LG. Following osteogenic differentiation procedures, calcium accumulation, alkaline phosphatase activity, and expression of osteogenic markers were significantly lower in HG compared with LG. Exposure of BFP–MSC to PRP significantly increased cell number and osteogenic differentiation potential, reaching comparable levels in LG and in HG. Thus, high‐glucose concentrations impair BFP–MSC growth and osteogenic differentiation. However, these detrimental effects are largely counteracted by PRP.     

Matryoshka procedure for Valve‐in‐Valve TAVI failure

Valve‐in‐valve transcatheter valve implantation (ViV‐TAVI) procedures for deteriorated bioprosthesis are an established therapeutic option for high‐risk patients. The presence of the fixed sewing ring of the bioprosthesis can hamper appropriate expansion of the TAVI. We present a case of a ViViV‐TAVI, as a salvage procedure for acute ViV‐TAVI failure.     

RPE65-Associated Retinopathies in the Italian Population: A Longitudinal Natural History Study

PurposeTo investigate the course of inherited retinal degenerations (IRD) due to mutations in the RPE65 gene.MethodsThis longitudinal multicentric retrospective chart-review study was designed to collect best corrected visual acuity (BCVA), Goldman visual field, optical coherence tomography (OCT), and electroretinography (ERG) measurements. The data, including imaging, were collected using an electronic clinical research form and were reviewed at a single center to improve consistency.ResultsFrom an overall cohort of 60 Italian patients with RPE65-associated IRD, 43 patients (mean age, 27.8 ± 19.7 years) were included and showed a mean BCVA of 2.0 ± 1.0 logMAR. Time-to-event analysis revealed a median age of 33.8 years and 41.4 years to reach low vision and blindness based on BCVA, respectively. ERG (available for 34 patients) showed undetectable responses in most patients (26; 76.5%). OCT (available for 31 patients) revealed epiretinal membranes in five patients (16.1%). Central foveal thickness significantly decreased with age at a mean annual rate of −0.6%/y (P = 0.044). We identified 43 different variants in the RPE65 gene in the entire cohort. Nine variants were novel. Finally, to assess genotype-phenotype correlations, patients were stratified according to the number of RPE65 loss-of-function (LoF) alleles. Patients without LoF variants showed significantly (P < 0.05) better BCVA compared to patients with one or two LoF alleles.ConclusionsWe described the natural course of RPE65-associated IRD in an Italian cohort showing for the first time a specific genotype-phenotype association. Our findings can contribute to a better management of RPE65-associated IRD patients.     

Integrative genetic, epigenetic and pathological analysis of paraganglioma reveals complex dysregulation of NOTCH signaling

Head and neck paragangliomas, rare neoplasms of the paraganglia composed of nests of neurosecretory and glial cells embedded in vascular stroma, provide a remarkable example of organoid tumor architecture. To identify genes and pathways commonly deregulated in head and neck paraganglioma, we integrated high-density genome-wide copy number variation (CNV) analysis with microRNA and immunomorphological studies. Gene-centric CNV analysis of 24 cases identified a list of 104 genes most significantly targeted by tumor-associated alterations. The “NOTCH signaling pathway” was the most significantly enriched term in the list (P = 0.002 after Bonferroni or Benjamini correction). Expression of the relevant NOTCH pathway proteins in sustentacular (glial), chief (neuroendocrine) and endothelial cells was confirmed by immunohistochemistry in 47 head and neck paraganglioma cases. There were no relationships between level and pattern of NOTCH1/JAG2 protein expression and germline mutation status in the SDH genes, implicated in paraganglioma predisposition, or the presence/absence of immunostaining for SDHB, a surrogate marker of SDH mutations. Interestingly, NOTCH upregulation was observed also in cases with no evidence of CNVs at NOTCH signaling genes, suggesting altered epigenetic modulation of this pathway. To address this issue we performed microarray-based microRNA expression analyses. Notably 5 microRNAs (miR-200a,b,c and miR-34b,c), including those most downregulated in the tumors, correlated to NOTCH signaling and directly targeted NOTCH1 in in vitro experiments using SH-SY5Y neuroblastoma cells. Furthermore, lentiviral transduction of miR-200s and miR-34s in patient-derived primary tympano-jugular paraganglioma cell cultures was associated with NOTCH1 downregulation and increased levels of markers of cell toxicity and cell death. Taken together, our results provide an integrated view of common molecular alterations associated with head and neck paraganglioma and reveal an essential role of NOTCH pathway deregulation in this tumor type.