Soft tissue augmentation procedures at second-stage surgery: a systematic review.

OBJECTIVES The aim of this systematic review was to evaluate the efficacy of different soft tissue augmentation/correction methods in terms of increasing the peri-implant width of keratinized mucosa (KM) and/or gain of soft tissue volume during second-stage surgery. MATERIALS AND METHODS Screening of two databases, MEDLINE (PubMed) and EMBASE (OVID), and hand search of related articles, were performed. Human studies reporting on soft tissue augmentation/correction methods around submucosally osseointegrated implants during second-stage surgery up to July 31, 2015 were considered. Quality assessment of the selected full-text articles was performed according to the Cochrane collaboration's tool to assess the risk of bias. RESULTS Overall, eight prospective studies (risk of bias: high) and two case series (risk of bias: high) were included. Depending on the surgical technique and graft material used, the enlargement of keratinized tissue (KT) ranged between -0.20 and 9.35 mm. An apically positioned partial-thickness flap/vestibuloplasty (APPTF/VP) in combination with a free gingival graft (FGG) or a xenogeneic graft material (XCM) was most effective. Applying a roll envelope flap (REF) or an APPTF in combination with a subepithelial connective tissue graft (SCTG), mean increases in soft tissue volumes of 2.41 and 3.10 mm, respectively, were achieved. Due to the heterogeneity of study designs, no meta-analysis could be performed. CONCLUSIONS Within the limitations of this review, regarding the enlargement of peri-implant KT, the APPTF in the maxilla and the APPTF/VP in combination with FGG or XCM in the lower and upper jaw seem to provide acceptable outcomes. To augment peri-implant soft tissue volume REF in the maxilla or APPTF + SCTG in the lower and upper jaw appear to be reliable treatment options. CLINICAL RELEVANCE The localization in the jaw and the clinical situation are crucial for the decision which second-stage procedure should be applied

The polymorphism L412F in TLR3 inhibits autophagy and is a marker of severe COVID-19 in males

The polymorphism L412F in TLR3 has been associated with several infectious diseases. However, the mechanism underlying this association is still unexplored. Here, we show that the L412F polymorphism in TLR3 is a marker of severity in COVID-19. This association increases in the sub-cohort of males. Impaired macroautophagy/autophagy and reduced TNF/TNFα production was demonstrated in HEK293 cells transfected with TLR3L412F-encoding plasmid and stimulated with specific agonist poly(I:C). A statistically significant reduced survival at 28 days was shown in L412F COVID-19 patients treated with the autophagy-inhibitor hydroxychloroquine (p = 0.038). An increased frequency of autoimmune disorders such as co-morbidity was found in L412F COVID-19 males with specific class II HLA haplotypes prone to autoantigen presentation. Our analyses indicate that L412F polymorphism makes males at risk of severe COVID-19 and provides a rationale for reinterpreting clinical trials considering autophagy pathways. Abbreviations: AP: autophagosome; AUC: area under the curve; BafA1: bafilomycin A1; COVID-19: coronavirus disease-2019; HCQ: hydroxychloroquine; RAP: rapamycin; ROC: receiver operating characteristic; SARS-CoV-2: severe acute respiratory syndrome coronavirus 2; TLR: toll like receptor; TNF/TNF-α: tumor necrosis factor

Pathogen-sugar interactions revealed by universal saturation transfer analysis

Many pathogens exploit host cell-surface glycans. However, precise analyses of glycan ligands binding with heavily modified pathogen proteins can be confounded by overlapping sugar signals and/or compounded with known experimental constraints. Universal saturation transfer analysis (uSTA) builds on existing nuclear magnetic resonance spectroscopy to provide an automated workflow for quantitating protein-ligand interactions. uSTA reveals that early-pandemic, B-origin-lineage severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike trimer binds sialoside sugars in an “end-on” manner. uSTA-guided modeling and a high-resolution cryo–electron microscopy structure implicate the spike N-terminal domain (NTD) and confirm end-on binding. This finding rationalizes the effect of NTD mutations that abolish sugar binding in SARS-CoV-2 variants of concern. Together with genetic variance analyses in early pandemic patient cohorts, this binding implicates a sialylated polylactosamine motif found on tetraantennary N-linked glycoproteins deep in the human lung as potentially relevant to virulence and/or zoonosis

Genetic mechanisms of critical illness in COVID-19.

Host-mediated lung inflammation is present1, and drives mortality2, in the critical illness caused by coronavirus disease 2019 (COVID-19). Host genetic variants associated with critical illness may identify mechanistic targets for therapeutic development3. Here we report the results of the GenOMICC (Genetics Of Mortality In Critical Care) genome-wide association study in 2,244 critically ill patients with COVID-19 from 208 UK intensive care units. We have identified and replicated the following new genome-wide significant associations: on chromosome 12q24.13 (rs10735079, P = 1.65 × 10-8) in a gene cluster that encodes antiviral restriction enzyme activators (OAS1, OAS2 and OAS3); on chromosome 19p13.2 (rs74956615, P = 2.3 × 10-8) near the gene that encodes tyrosine kinase 2 (TYK2); on chromosome 19p13.3 (rs2109069, P = 3.98 ×  10-12) within the gene that encodes dipeptidyl peptidase 9 (DPP9); and on chromosome 21q22.1 (rs2236757, P = 4.99 × 10-8) in the interferon receptor gene IFNAR2. We identified potential targets for repurposing of licensed medications: using Mendelian randomization, we found evidence that low expression of IFNAR2, or high expression of TYK2, are associated with life-threatening disease; and transcriptome-wide association in lung tissue revealed that high expression of the monocyte-macrophage chemotactic receptor CCR2 is associated with severe COVID-19. Our results identify robust genetic signals relating to key host antiviral defence mechanisms and mediators of inflammatory organ damage in COVID-19. Both mechanisms may be amenable to targeted treatment with existing drugs. However, large-scale randomized clinical trials will be essential before any change to clinical practice

Common, low-frequency, rare, and ultra-rare coding variants contribute to COVID-19 severity

The combined impact of common and rare exonic variants in COVID-19 host genetics is currently insufficiently understood. Here, common and rare variants from whole-exome sequencing data of about 4000 SARS-CoV-2-positive individuals were used to define an interpretable machine-learning model for predicting COVID-19 severity. First, variants were converted into separate sets of Boolean features, depending on the absence or the presence of variants in each gene. An ensemble of LASSO logistic regression models was used to identify the most informative Boolean features with respect to the genetic bases of severity. The Boolean features selected by these logistic models were combined into an Integrated PolyGenic Score that offers a synthetic and interpretable index for describing the contribution of host genetics in COVID-19 severity, as demonstrated through testing in several independent cohorts. Selected features belong to ultra-rare, rare, low-frequency, and common variants, including those in linkage disequilibrium with known GWAS loci. Noteworthily, around one quarter of the selected genes are sex-specific. Pathway analysis of the selected genes associated with COVID-19 severity reflected the multi-organ nature of the disease. The proposed model might provide useful information for developing diagnostics and therapeutics, while also being able to guide bedside disease management. © 2021, The Author(s)

SARS-CoV-2 susceptibility and COVID-19 disease severity are associated with genetic variants affecting gene expression in a variety of tissues

Variability in SARS-CoV-2 susceptibility and COVID-19 disease severity between individuals is partly due to genetic factors. Here, we identify 4 genomic loci with suggestive associations for SARS-CoV-2 susceptibility and 19 for COVID-19 disease severity. Four of these 23 loci likely have an ethnicity-specific component. Genome-wide association study (GWAS) signals in 11 loci colocalize with expression quantitative trait loci (eQTLs) associated with the expression of 20 genes in 62 tissues/cell types (range: 1:43 tissues/gene), including lung, brain, heart, muscle, and skin as well as the digestive system and immune system. We perform genetic fine mapping to compute 99% credible SNP sets, which identify 10 GWAS loci that have eight or fewer SNPs in the credible set, including three loci with one single likely causal SNP. Our study suggests that the diverse symptoms and disease severity of COVID-19 observed between individuals is associated with variants across the genome, affecting gene expression levels in a wide variety of tissue types

A first update on mapping the human genetic architecture of COVID-19

peer reviewe

Soft tissue augmentation around osseointegrated and uncovered dental implants: a systematic review.

OBJECTIVES The aim was to compile the current knowledge about the efficacy of different soft tissue correction methods around osseointegrated, already uncovered and/or loaded (OU/L) implants with insufficient soft tissue conditions. Procedures to increase peri-implant keratinized mucosa (KM) width and/or soft tissue volume were considered. MATERIALS AND METHODS Screening of two databases: MEDLINE (PubMed) and EMBASE (OVID), and manual search of articles were performed. Human studies reporting on soft tissue augmentation/correction methods around OU/L implants up to June 30, 2016, were considered. Quality assessment of selected full-text articles to weight risk of bias was performed using the Cochrane collaboration's tool. RESULTS Overall, four randomized controlled trials (risk of bias = high/low) and five prospective studies (risk of bias = high) were included. Depending on the surgical techniques and graft materials, the enlargement of keratinized tissue (KT) ranged between 1.15 ± 0.81 and 2.57 ± 0.50 mm. The apically positioned partial thickness flap (APPTF), in combination with a free gingival graft (FGG), a subepithelial connective tissue graft (SCTG), or a xenogeneic graft material (XCM) were most effective. A coronally advanced flap (CAF) combined with SCTG in three, combined with allogenic graft materials (AMDA) in one, and a split thickness flap (STF) combined with SCTG in another study showed mean soft tissue recession coverage rates from 28 to 96.3 %. STF combined with XCM failed to improve peri-implant soft tissue coverage. CONCLUSIONS The three APPTF-techniques combined with FGG, SCTG, or XCM achieved comparable enlargements of peri-implant KT. Further, both STF and CAF, both in combination with SCTG, are equivalent regarding recession coverage rates. STF + XCM and CAF + AMDA did not reach significant coverage. CLINICAL RELEVANCE In case of soft tissue deficiency around OU/L dental implants, the selection of both an appropriate surgical technique and a suitable soft tissue graft material is of utmost clinical relevance

COVID-19 Host Genetics Initiative. A first update on mapping the human genetic architecture of COVID-19

The COVID-19 pandemic continues to pose a major public health threat, especially in countries with low vaccination rates. To better understand the biological underpinnings of SARS-CoV-2 infection and COVID-19 severity, we formed the COVID-19 Host Genetics Initiative1. Here we present a genome-wide association study meta-analysis of up to 125,584 cases and over 2.5 million control individuals across 60 studies from 25 countries, adding 11 genome-wide significant loci compared with those previously identified2. Genes at new loci, including SFTPD, MUC5B and ACE2, reveal compelling insights regarding disease susceptibility and severity.</p