Πέμπτη 4 Αυγούστου 2022

COVID-19 vaccine effectiveness against symptomatic SARS-CoV-2 infection during Delta-dominant and Omicron-dominant periods in Japan: a multi-center prospective case-control study (FASCINATE study)

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Abstract
Background
Although several COVID-19 vaccines initially showed high efficacy, there have been concerns due to waning immunity and the emergence of variants with immune escape capacity.
Methods
A test-negative design case-control study was conducted in 16 healthcare facilities in Japan during the Delta-dominant period (August-September 2021) and the Omicron-dominant period (January-March 2022). Vaccine effectiveness (VE) against symptomatic SARS-CoV-2 infection was calculated for 2 doses for the Delta-dominant period and 2 or 3 doses for the Omicron-dominant period, compared to unvaccinated individuals.
Results
The analysis included 5795 individuals with 2595 (44.8%) cases. Among vaccinees, 2242 (55.8%) received BNT162b2 and 1624 (40.4%) received mRNA-1273 at manufacturer-recommended intervals. During the Delta-dominant period, VE was 88% (95% CI: 82-93) 14 days-3 months after dose 2 and 87% (95% CI: 38-97) 3-6 months a fter dose 2. During the Omicron-dominant period, VE was 56% (95% CI: 37-70) 14 days-3 months since dose 2, 52% (95% CI: 40-62) 3-6 months after dose 2, 49% (95% CI: 34-61) 6 + months after dose 2, and 74% (95% CI: 62-83) 14 + days after dose 3. Restricting to individuals at high risk of severe COVID-19 and additional adjustment for preventive measures (i.e. mask-wearing/high-risk behaviors) yielded similar estimates, respectively.
Conclusions
In Japan where most are infection-naïve and strict prevention measures are maintained regardless of vaccination status, 2-dose mRNA vaccines provided high protection against symptomatic infection during the Delta-dominant period and moderate protection during the Omicron-dominant period. Among individuals who received an mRNA booster dose, VE recovered to a high level.
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Effects of boosted mRNA and adenoviral‐vectored vaccines on immune responses to omicron BA.1 and BA.2 following the heterologous CoronaVac/AZD1222 vaccination

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Abstract

Introduction

The coronavirus 2019 omicron variant has surged rapidly and raises concerns about immune evasion even in individuals with complete vaccination because it harbors mutations. Here, we examine the capability of booster vaccination following CoronaVac/AZD1222 prime to induce neutralizing antibodies (NAbs) against omicron (BA.1 and BA.2) and T-cell responses.

Methods

A total of 167 participants primed with heterologous CoronaVac/AZD1222 for 4-5 months were enrolled to receive AZD1222, BNT162b2, or mRNA-1273 as a third dose. Reactogenicity was recorded. Immunogenicity analyses of SARS-CoV-2 binding antibodies were measured using ELISA. The neutralizing antibody (NAb) titers against omicron BA.1 and BA.2 were determined using the focus reduction neutralization test (FRNT50) and total interferon-gamma (IFN-γ) responses were measured to observe the T cell activation.

Results

A substantial loss in neutralizing potency to omicron variant was found at 4 to 5 months after receiving the heterologous CoronaVac/AZD1222. Following booster vaccination, a significant increase in binding antibodies and neutralizing activities toward delta and omicron variants was observed. Neutralization to omicron BA.1 and BA.2 were comparable, showing the highest titers after boosted mRNA-1273 followed by BNT162b2 and AZD1222. In addition, individuals boosted with mRNA vaccines develop a T cell response to spike protein while those boosted with AZD1222 did not. Reactogenicity was mild to moderate without serious adverse events.

Conclusions

Our findings demonstrated that mRNA booster vaccination is able to overcome waning immunity to provide antibodies that neutralize omicron BA.1 and BA.2, as well as a T cell response.

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Prognostic capacity of the transcriptional expression of lactate dehydrogenase A in patients with head and neck squamous cell carcinoma

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Abstract

Background

To analyze the relationship between the transcriptional expression of lactate dehydrogenase A (LDHA) and the disease control in patients with a head and squamous cell carcinoma (HNSCC).

Methods

We determined the transcriptional expression of LDHA in 110 HNSCC patients treated with surgery.

Results

Five-year disease-free survival for patients with a high transcriptional expression of LDHA (n = 51) was 39.2% (95% confidence interval [CI]: 25.3%–53.1%), and for patients with a low expression (n = 59), it was 63.6% (95% CI: 51.1%–76.1%) (p = 0.004). According to the results of a multivariate analysis, patients with a high transcriptional expression of LDHA had a 3.4-fold increased risk of tumor recurrence. Patients with a high transcriptional expression of LDHA tended to show a higher intensity of immunohistochemical expression of LDHA at the tumor cells (p = 0.086).

Conclusion

In HNSCC patients treated with surgery, a high transcriptional expression of LDHA was associated with a significant decrease in disease-free survival.
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Epstein-Barr Virus–Positive Plasma Cell Neoplasm of Nasal Cavity in an Immunocompetent Adult

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This case report describes patient in their 40s with a medical history of sleep apnea and diabetes and no history of immunosuppression who presented with left-sided nasal obstruction for 1 year and was found to have an Epstein-Barr virus–positive plasmacytoma.
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Downregulation of miRNA‐26 in Chronic Periodontitis Interferes with Innate Immune Responses and Cell Migration by Targeting Phospholipase C Beta 1 (PLCB1)

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Abstract

Aim

To evaluate the potential role of miR-26 family members in periodontal pathogenesis by assessing innate immune responses to periopathic bacteria and regulation of cytoskeletal organization.

Methods

Expression of miR-26a-5p and miR-26b-5p was quantified in gingival biopsies derived from healthy and periodontally diseased subjects before and after non-surgical (scaling and root planing) therapy by RT-qPCR. Global pathway analysis and luciferase assays were performed for target identification and validation. Cytokine expression was assessed in miR-26a-5p transfected human oral keratinocytes upon stimulation with either live Porphyromonas gingivalis (Pg), Aggregatibacter actinomycetocomitans (Aa) or Pg LPS. Wound closure assays were performed in cells transfected with miR-26a-5p, while the impact on cytoskeletal organization was assessed by F-actin staining.

Results

miR-26a-5p and miR-26b-5p are downregulated in diseased gingiva and restored 4-6 weeks post-therapy to levels comparable with healthy subjects. Target validation assays identified phospholipase c beta 1 (PLCB1) as a bona-fide novel target exhibiting antagonistic expression pattern in disease and post-therapy cohorts. miR-26a-5p transfected cells secreted higher levels of cytokine/chemokines upon stimulation with periopathogens and demonstrated impaired cell migration and cytoskeletal rearrangement.

Conclusion

Downregulated miR-26a-5p levels in periodontal inflammation may interfere with key cellular functions that may have significant implications for host defense and wound healing.
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Transoral Laser Microsurgery in Recurrent Laryngeal Cancer: A Systematic Review and Meta‐analysis

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Transoral Laser Microsurgery in Recurrent Laryngeal Cancer: A Systematic Review and Meta-analysis

The aim of this systematic review and meta-analysis was to determine the oncological outcomes of salvage transoral laser microsurgery (TLM) in the treatment of patients suffering from recurrent laryngeal cancer. We demonstrated that TLM is a valuable treatment option for the management of locally recurrent laryngeal carcinoma if performed by experienced surgeons and following rigorous patients' selection criteria. Further studies should be conducted to define stage-based clinical guidelines.


Objective

To determine the oncological outcomes of salvage transoral laser microsurgery (TLM) in the treatment of patients suffering from recurrent laryngeal cancer.

Methods

PubMed/MEDLINE, Cochrane Library, and Scopus databases were searched. English language, original studies investigating oncological outcomes of TLM in adult patients with recurrent laryngeal cancer were included. Data were pooled using a distribution-free approach for estimating summary local control (LC), disease-specific survival (DSS), and overall survival (OS) curves with random effects.

Results

Two hundred and thirty-five patients underwent salvage TLM after primary (chemo)radiotherapy. The mean follow-up time was 60.8 months (95% CI: 32.7–88.9). Estimated pooled LC rates (95% CI) at 1, 3 and 5 years were 74.2% (61.7–89.4), 53.9% (38.5–75.3), and 39.1% (25.2–60.8). Estimated pooled DSS rates (95% CI) at 1, 3 and 5 years were 88.4% (82.0–95.3), 67.8% (50.9–90.3), and 58.9% (42.7–81.1). Two hundred and seventy-one patients underwent TLM after primary laser treatment. The mean follow-up time was 70.9 months (95% CI: 36.9–104.9). Estimated pooled LC rates (95% CI) at 1, 3 and 5 years were 72.2% (64.7–80.6), 53.2% (42.2–66.9), and 40.4% (29.6–55.2). Estimated pooled DSS rates (95% CI) at 1, 3 and 5 years were 92.1% (85.5–99.1), 77.0% (64.4–92.0), and 67.1% (51.6–87.3).

Conclusions

TLM is a valuable treatment option for the management of locally recurrent laryngeal carcinoma if performed by experienced surgeons and following rigorous patients' selection criteria. Further studies should be conducted to define stage-based clinical guidelines.

Level of Evidence

NA Laryngoscope, 2022
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Survival and complications of implant‐supported cantilever fixed dental prostheses with zirconia and metal frameworks: A retrospective cohort study

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Abstract

Background

Current evidence about long-term survival of all-ceramic implant-supported cantilever fixed dental prostheses (cFDP) is limited.

Purpose

To evaluate the survival and complication rates of all-ceramic and metal–ceramic implant-supported cFDPs located in anterior and posterior sites, under consideration of risk factors.

Methods of study

The retrospective analysis compared an experimental group (75 implant-supported cFDPs among 48 patients [mean age 60.47 ± 9.25 years; 21 men]; mean observation period 3.56 years) with a control group (300 implant-supported non-cantilever FDPs [ncFDP] among 241 patients [mean age 62.85 ± 10.72 years; 109 men]; mean observation period 7.25 years). Kaplan–Meier estimates were used to describe the long-term survival and success of both groups. Log-rank tests were used for group comparisons. Mixed-effects Cox proportional hazards regression models were used to examine the effects of restoration- and site-specific risk factors. A random intercept was included in the models to take multiple FDPs per patient into account.

Results

Five-year cumulative survival until loss of restoration was 97.1% (95% confidence interval [CI] 0.93–1.00) for cFDPs and 97.0% (95% CI 0.95–0.99) for ncFDPs. Ten-year survival was 93.7% (95% CI 0.86–1.00) for cFDPs and 92.8% (95% CI 0.87–0.98) for ncFDPs, no difference between the survival curves of these groups was observed. Success differed between cFDPs and ncFDPs (p Log  = 0.002), zirconia and metal frameworks (p Log  < 0.001), and provisional and definitive cements (p Log  = 0.025). The effects of the variables "framework material" and "attachment method" were confirmed in a mixed-effects Cox regression model. Loss of retention was the predominant complication for both cFDPs and ncFDPs and usually affected provisionally cemented FDPs.

Conclusions

cFDPs do not differ from ncFDPs with regard to long-term failure, whereas additional complications were higher for cFDPs. Fewer complications were observed for zirconia frameworks without occlusal veneers and definitive cemented FDPs.

Clinical trial registration: the trial has no registration number because it commenced before January 31, 2017.
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Does the presence of third molars during sagittal split mandibular ramus osteotomy favour complications? Systematic review and meta-analysis

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The aim of this systematic review and meta-analysis was to assess whether the presence of inferior third molars during sagittal split mandibular ramus osteotomy increases the risk of intraoperative and postoperative complications. The PRISMA protocol was followed in this study, and the review was registered in the PROSPERO database (CRD42020147642). A search was conducted in the MEDLINE (PubMed), Web of Science, Cochrane Central, and Scopus databases on November 1, 2021. Nineteen articles were included, and the variables analysed were unfavourable fractures, infection, neurosensory disturbance, removal of osteosynthesis material, and duration of surgery. (Source: International Journal of Oral and Maxillofacial Surgery)
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Exosomes rewire the cartilage microenvironment in osteoarthritis: from intercellular communication to therapeutic strategies

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International Journal of Oral Science, Published online: 05 August 2022; doi:10.1038/s41368-022-00187-z

Exosomes rewire the cartilage microenvironment in osteoarthritis: from intercellular communication to therapeutic strategies
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Susceptibility to mice and potential evolutionary characteristics of porcine deltacoronavirus

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ABSTRACT

Porcine deltacoronavirus (PDCoV) is a novel coronavirus that causes diarrhoea in suckling piglets and has the potential for cross-species transmission, posing a threat to animal and human health. However, the susceptibility profile of different species of mice to PDCoV infection and its evolutionary characteristics are still unclear. In current study, we identified that BALB/c and Kunming mice are susceptible to PDCoV. Our results showed that there were obvious lesions in intestinal and lung tissues from the infected mice. PDCoV RNAs were detected in the lung, kidney and intestinal tissues from the infected mice of both strains, and there existed wider tissue tropism in the PDCoV-infected BALB/c mice. The RNA and protein levels of aminopeptidase N from mice (mAPN) were relatively high in the kidney and intestinal tissues and obviously increased after PDCoV infection. The viral specific IgG and neutralizing antibodies against PDCoV were detected in serum from the infected mice. An interesting finding was that, two key amino acid mutations D138H and Q641K in the S protein were identified from the PDCoV-infected mice. The essential roles of these two mutations for PDCoV-adaptive evolution were confirmed by cryo-EM structure model analysis. The evolutionary characteristics of PDCoV among Deltacoronaviruses (δ-CoVs) were further analyzed. δ-CoVs from multiple mammals are closely related based on the phylogenetic analysis. The codon usage analysis demonstrated similar codon usage patterns were used by most of the mammalian δ-CoVs at the global codon usage, synonymous codon usage and amino acid usage levels. These results may provide more insights into the evolution, host ranges and the cross species potential of PDCoV.

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