Lateral Ridge Augmentation with Guided Bone Regeneration Using Particulate Bone Substitutes and Injectable Platelet-Rich Fibrin in a Digital Workflow: 6 Month Results of a Prospective Cohort Study Based on Cone-Beam Computed Tomography Data

This study aimed to test whether or not a digital workflow for GBR with particulate bone substitutes and injectable platelet-rich fibrin improved the thickness of the hard tissue compared to the conventional workflow. 26 patients in need of lateral bone augmentation were enrolled. GBR with particulate bone substitutes and injectable platelet-rich fibrin was performed in all patients. Patients were divided into two groups: control (conventional workflow; n = 14) and test (digital workflow; n = 12). CBCT scans were performed before surgery, immediately after wound closure, and 6 months post-surgery, and the labial thickness of the hard tissue (LT) was assessed at 0–5 mm apical to the implant shoulder (LT0–LT5) at each time point. A total of 26 patients were included in this study. After wound closure, the test group showed significantly greater thickness in LT0–LT2 than the control group (LT0: test: 4.31 ± 0.73 mm, control: 2.99 ± 1.02 mm; LT1: test: 4.55 ± 0.69 mm, control: 3.60 ± 0.96 mm; LT2: test: 4.76 ± 0.54 mm, control: 4.05 ± 1.01 mm; p < 0.05). At 6 months, significant differences in LT0–LT1 were detected between the groups (LT0: test: 1.88 ± 0.57 mm, control: 1.08 ± 0.60 mm; LT1: test: 2.36 ± 0.66 mm, control: 1.69 ± 0.58 mm; p < 0.05). Within the limitations of this study, the use of digital workflow in GBR with particulate bone substitutes and i-PRF exerted a positive effect on the labial thickness of hard tissue in the coronal portion of the implant after wound closure and at 6 months.

Structural insights into tick-borne encephalitis virus neutralization and animal protection by a therapeutic antibody

Tick-borne encephalitis virus (TBEV) causes about 5-6 thousand cases annually, while there is still no effective treatment for this virus. To fill this gap, a high-affinity chimeric anti-TBEV antibody ch14D5 has previously been constructed, and high protective activity in a murine TBEV model has been shown for this antibody. However, the mechanism of action of this antibody and the recognized epitope have not been known yet. In this study, it is shown by X-ray crystallography that this antibody recognizes a unique epitope on the lateral ridge of the D3 domain of glycoprotein E, which is readily accessible for binding. The orientation of this antibody relative to the virion surface makes bivalent binding possible, which facilitates the cross-linking of glycoprotein E molecules and thus blocking of surface rearrangements required for infection. Since the antibody tightly binds to this protein even at pH ~ 5.0, it locks the virion in an acidic environment inside the late endosomes or phagosomes and, therefore, effectively blocks the fusion of the viral and endosomal/phagosomal membranes. We believe that this is why the ch14D5 antibody does not induce an antibody-dependent enhancement of infection in vivo, which is critical in the development of antibody-based therapeutic agents. In addition, the structure of the antibody-glycoprotein E interface can be used for the rational design of this antibody for enhancing its properties.

Retrospective Study on Tooth Shell Technique Using Endodontically Treated Teeth in Lateral Ridge Augmentation

Autogenous dentin has been reported to be a suitable grafting material for certain indications. The purpose of this study was to assess the feasibility of using endodontically treated teeth for this application. In the present retrospective study, one-stage augmentation of lateral ridge defects with a dentin shell and particulate (tooth shell technique (TST)) either obtained from endodontically treated teeth (ETT, 17 patients with 21 implants) or non-endodontically treated teeth (NETT, 17 patients with 24 implants) were analyzed. Follow-up was conducted 3 months after augmentation. The target parameters were biological complications, horizontal hard tissue loss, osseointegration, and the integrity of the buccal lamella. Only minor complications occurred in three implants from three patients, including two cases of wound dehiscence (one each in ETT and NETT) and a localized three-walled defect in the NETT group, which was solved by re-augmentation. All the implants were osseointegrated and the integrity of the buccal lamella was preserved. The mean difference of the resorption of the crestal width and the buccal lamella did not differ statistically between the two groups. As TST using ETT showed, the results comparable to those of NETT dentin from endodontically treated teeth can be safely applied with predictable results for this grafting technique.

Comparing the Efficacy of a Microperforated Titanium Membrane for Guided Bone Regeneration with an Existing Mesh Retainer in Dog Mandibles

Acute-type lateral ridge defects (25 mm × 6 mm × 5 mm) were bilaterally created in the mandibles of four dogs (two defects per animal). The defects were reconstructed with particulate autologous bone and covered with a microperforated titanium membrane (Ti-honeycomb membrane, TiHM) or an existing conventional titanium mesh as control. The samples were dissected after 16 weeks postoperatively and processed for radiographic, histologic, and histomorphometric analyses. Regenerated tissue and bone volume were significantly larger in the TiHM group than in the control group (p = 0.05; p = 0.049). In contrast, bone mineral density was similar between the two groups. Histomorphometric analysis revealed that the regenerated bone area and calcific osseous area were larger in the TiHM group than in the control group; however, the differences were not significant. The efficacy of TiHM was generally satisfactory with the potential to become a standard tool for the GBR procedure; however, early membrane exposure will be a major problem to overcome.

The role of marshall bundle epicardial connections in atrial tachycardias after atrial fibrillation ablation

Funding Acknowledgements Type of funding sources: None. Background Atrial tachycardias (ATs) are often seen in the context of AF ablation. Objectives We evaluated the role of the Marshall bundle (MB) network in left atrial (LA) ATs using high-density high-spatial resolution 3D mapping. Methods 199 post-AF ablation LA tachycardias were mapped in 140 consecutive patients (112 (80%) males, mean age: 61.8 years); 133 (66.8%) were macro-reentrant and 66 (33.2%) were scar-related re-entry. MB-dependent perimitral AT (PMAT) was diagnosed where the difference between the post pacing interval and the tachycardia cycle length (PPI-TCL) was &lt;20ms in parts of the expected MB-dependent perimitral circuit (within the VOM, the ridge between the left pulmonary veins and LA appendage (LAA), the anterior LA and between 6- and 11-o’clock of the mitral annulus) and the PPI-TCL was &gt;20ms in areas bypassed by the VOM (the distal coronary sinus (CS), the posterior LA and the mitral isthmus). MB-related re-entry was diagnosed by PPI-TCL &lt;20ms at the left lateral ridge, posterior base of LAA, inferolateral LA or VOM ostium; and PPI-TCL &gt;20ms in the septal annulus. Typically, in MB-dependent localized re-entry, the earliest activation was found along the MB-LA endocardial connection or MB-CS epicardial connection. Results The MB network was found to participate in 60 (30.2%) re-entrant ATs, 31 PMATs and 29 localized re-entries. High-frequency multiphasic fragmented electrograms with long duration were often recorded endocardially or epicardially at the MB-LA or MB-CS connections. The amplitude and duration of these signals were 0.5 ± 0.79 mV and 65 ± 40 ms for MB-PMATs and 0.26 ± 0.28mV and 122 ± 67 ms for MB-localized re-entries. Unipolar EGMs at the site of endocardial-epicardial breakthrough had a rS pattern in all MB-related ATs. Of 60 MB-related ATs, 49 (81.6%) terminated with RF ablation, 44 (73.3%) at the MB-LA junction and 5 (8.3%) at the MB-CS junction, while 9 (15%) terminated after 2.5-5 cc of alcohol infusion inside the vein of Marshall (VOM). Of the 31 MB-related macroreentrant ATs, 17 (54.8%) terminated at the MB-LA junction, 5 (16.1%) at the MB-CS junction and 7 (22.6%) with alcohol infusion inside the VOM. Two macroreentries (6.5%) using the MB did not terminate with RF energy either endocardially at the MB-LA junction or epicardially at the MB-CS junction, and we were unable to identify or cannulate the VOM for ethanol infusion. Of the 29 localized re-entrant ATs using the MB, 27 (93.1%) terminated at the MB-LA junction, none terminated at the MB-CS junction and 2 (6.9%) terminated after alcohol infusion. After a mean follow up of 12 months, only 4 patients (6.7%) had AT recurrence. Conclusions MB re-entrant ATs accounted for up to 29% of the left ATs after AF ablation. Ablation of the MB-LA or CS-MB connections or alcohol infusion inside the VOM is required to treat these arrhythmias. Abstract Figure.

Broad and potent neutralizing human antibodies to tick-borne flaviviruses protect mice from disease

Tick-borne encephalitis virus (TBEV) is an emerging human pathogen that causes potentially fatal disease with no specific treatment. Mouse monoclonal antibodies are protective against TBEV, but little is known about the human antibody response to infection. Here, we report on the human neutralizing antibody response to TBEV in a cohort of infected and vaccinated individuals. Expanded clones of memory B cells expressed closely related anti-envelope domain III (EDIII) antibodies in both groups of volunteers. However, the most potent neutralizing antibodies, with IC50s below 1 ng/ml, were found only in individuals who recovered from natural infection. These antibodies also neutralized other tick-borne flaviviruses, including Langat, louping ill, Omsk hemorrhagic fever, Kyasanur forest disease, and Powassan viruses. Structural analysis revealed a conserved epitope near the lateral ridge of EDIII adjoining the EDI–EDIII hinge region. Prophylactic or early therapeutic antibody administration was effective at low doses in mice that were lethally infected with TBEV.

Retrospective Study: Lateral Ridge Augmentation Using Autogenous Dentin: Tooth-Shell Technique vs. Bone-Shell Technique

In the literature, autogenous dentin is considered a possible alternative to bone substitute materials and autologous bone for certain indications. The aim of this proof-of-concept study was to use autogenous dentin for lateral ridge augmentation. In the present retrospective study, autogenous dentin slices were obtained from teeth and used for the reconstruction of lateral ridge defects (tooth-shell technique (TST): 28 patients (15 females, 13 males) with 34 regions and 38 implants). The bone-shell technique (BST) according to Khoury (31 patients (16 females, 15 males) with 32 regions and 41 implants) on autogenous bone served as the control. Implants were placed simultaneously in both cases. Follow-up was made 3 months after implantation. Target parameters during this period were clinical complications, horizontal hard tissue loss, osseointegration, and integrity of the buccal lamella. The prosthetic restoration with a fixed denture was carried out after 5 months. The total observation period was 5 months. A total of seven complications occurred. Of these, three implants were affected by wound dehiscences (TST: 1, BST: 2) and four by inflammations (TST: 0, BST: 4). There were no significant differences between the two groups in terms of the total number of complications. One implant with TST exhibited a horizontal hard tissue loss of 1 mm and one with BST of 0.5 mm. Other implants were not affected by hard tissue loss. There were no significant differences between the two groups. Integrity of the buccal lamella was preserved in all implants. All implants were completely osseointegrated in TST and BST. All implants could be prosthetically restored with a fixed denture 5 months after augmentation. TST showed results comparable to those of the BST. Dentin can therefore serve as an alternative material to avoid bone harvesting procedures and thus reduce postoperative discomfort of patients.

Monoclonal antibodies targeting the influenza virus N6 neuraminidase

Influenza A viruses are a diverse species that include 16 hemagglutinin (HA) subtypes and 9 neuraminidase (NA) subtypes. While the antigenicity of many HA subtypes is reasonably well studied, less is known about NA antigenicity, especially when it comes to non-human subtypes that only circulate in animal reservoirs. The N6 NA subtypes are mostly found in viruses infecting birds. However, they have also been identified in viruses that infect mammals, such as swine and seals. More recently, highly pathogenic H5N6 subtype viruses have caused rare infections and mortality in humans. Here, we generated murine mAbs to the N6 NA, characterized their breadth and antiviral properties in vitro and in vivo and mapped their epitopes by generating escape mutant viruses. We found that the antibodies had broad reactivity across the American and Eurasian N6 lineages, but relatively little binding and inhibition of the H5N6 NA. Several of the antibodies exhibited strong NA inhibition activity and some also showed activity in the antibody dependent cellular cytotoxicity reporter assay and neutralization assay. In addition, we generated escape mutant viruses for six monoclonal antibodies and found mutations on the lateral ridge of the NA. Lastly, we observed variable protection in H4N6 and H5N6 mouse challenge models when the antibodies were given prophylactically.ImportanceThe N6 NA has recently gained prominence due to the emergence of highly pathogenic H5N6 viruses. Currently, there is limited characterization of the antigenicity of avian N6 neuraminidase. Our data is an important first step towards a better understanding of the N6 NA antigenicity.