Αρχειοθήκη ιστολογίου

Αλέξανδρος Γ. Σφακιανάκης
ΩτοΡινοΛαρυγγολόγος
Αναπαύσεως 5
Άγιος Νικόλαος Κρήτη 72100
2841026182
6032607174

Κυριακή 29 Ιανουαρίου 2023

Novel Murine Glioblastoma Models That Reflect the Immunotherapy Resistance Profile of Human Disease

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Abstract
Background
The lack of murine glioblastoma models that mimic the immunobiology of human disease has impeded basic and translational immunology research. We therefore developed murine glioblastoma stem cell lines derived from Nestin-CreERT2QkL/L; Trp53L/L; PtenL/L (QPP) mice driven by clinically relevant genetic mutations common in human glioblastoma. This study aims to determine the immune sensitivities of these QPP lines in immunocompetent hosts and underlying mechanisms.
Methods
The differential responsiveness of QPP lines was assessed in the brain and flank in untreat ed, anti-PD-1, or anti-CTLA-4 treated mice. The impact of genomic landscape on responsiveness of each tumor was measured through whole exome sequencing. The immune microenvironments of sensitive (QPP7) versus resistant (QPP8) lines were compared in the brain using flow cytometry. Drivers of flank sensitivity versus brain resistance were also measured for QPP8.
Results
QPP lines are syngeneic to C57BL/6J mice and demonstrate varied sensitivities to T cell immune checkpoint blockade ranging from curative responses to complete resistance. Infiltrating tumor immune analysis of QPP8 reveals improved T cell fitness and augmented effector to suppressor ratios when implanted subcutaneously (sensitive), which are absent upon implantation in the brain (resistant). Upregulation of PD-L1 across the myeloid stroma acts to establish this state of immune privilege in the brain. In contrast, QPP7 responds to checkpoint immunotherapy even in the brain likely resulting from its elevated neoa ntigen burden.
Conclusions
These syngeneic QPP models of glioblastoma demonstrate clinically-relevant profiles of immunotherapeutic sensitivity and potential utility for both mechanistic discovery and evaluation of immune therapies.
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18F-THK5351 PET Can Evaluate Tumor Extension in Intravascular Large B-Cell Lymphoma: Comparison With: 11: C-Methionine PET and: 18: F-FDG PET

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imageA 79-year-old man presenting with gait disturbance and cognitive decline was diagnosed with intravascular large B-cell lymphoma (IVLBCL) by random skin biopsy. Some IVLBCL lesions were identified by PET examinations using 11C-methionine, 18F-FDG, and 18F-THK5351. 11C-methionine and 18F-FDG uptake, which likely reflects the presence of the lymphoma cells themselves, increased clearly in the left putamen but weakly in the left deep white matter. 18F-THK5351 uptake increased in all lesions, likely reflecting perivascular astrogliosis caused by IVLBCL. Hence, 18F-THK5351 PET can evaluate tumor extension in IVLBCL lesions wh ere 11C-methionine and 18F-FDG PET may fail in its visualization.
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68Ga-DOTA.SA.FAPI as a Potential, Noninvasive Diagnostic Probe for Recurrent and Metastatic Adrenocortical Carcinoma: A Head-to-Head Comparison With: 18: F-FDG

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imageMetastatic or recurrent adrenocortical carcinoma (ACC) is a potentially fatal malignancy, which poses major challenges in disease management owing to lack of effective systemic therapies. The drastically reduced survival rates require prompt identification of selective molecules for development of targeted therapeutics. We evaluated the squaric acid containing FAPI derivative, DOTA.SA.FAPI (FAPI), as a potential diagnostic probe in 2 cases of histopathologically proven metastatic and recurrent ACC. Both patients underwent 18F-FDG and 68Ga-FAPI PET/CT scans for comparative analysis. 68Ga-DOTA.SA.FAPI emerged as an excellen t diagnostic agent for ACC and performed similar to 18F-FDG.
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Bone Scan With Pulmonary Uptake in Scleroderma

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imageWe present a 61-year-old woman with a history of scleroderma and suspicion of osteomyelitis in her left wrist. She underwent a 3-phase bone scan for evaluation of osteomyelitis. Incidentally, the scan showed bilateral pulmonary MDP uptake, especially in lower lobes, which was proven to be due to the nonfibrotic form of nonspecific interstitial pneumonia.
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Transmission of Mpox: A narrative review of environmental, viral, host and population factors in relation to the 2022 international outbreak

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Abstract

Monkeypox virus (mpox) has spread globally. Emerging studies have now provided evidence regarding mpox transmission, that can inform rational evidence-based polices and reduce misinformation on this topic. We aimed to review the evidence on transmission of the virus. Real-world studies have isolated viable virus from high touch surfaces for as long as 15 days. Strong evidence suggests that current circulating monkeypox has evolved from previous outbreaks outside of Africa, but it is yet unknown whether these mutations may lead to an inherently increased infectivity of the virus. Strong evidence also suggests that the main route of current mkeypox transmission is sexual; through either close contact or directly, with detection of culturable virus in saliva, nasopharynx and sperm for prolonged periods and the presence of rashes mainly in genital areas. The milder clinical presentations and potential presence of presymptomatic transmission in the current circulating variant compared to previous clades, as well as the dominance of spread amongst men who have sex with men (MSMs) suggests that mpox has a developed distinct clinical phenotype that has increased its transmissibility. Increased public awareness of mpox transmission modalities may lead to earliar detection of the spillover of new cases into other groups.

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The influence of horizontal glass fiber posts on fracture strength and fracture pattern of endodontically treated teeth: A systematic review and meta‐analysis of in vitro studies

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Abstract

Purpose

This systematic review and meta-analysis aimed to summarize available evidence regarding the effect of horizontal glass fiber posts (HGFP) on fracture strength and fracture pattern of endodontically treated teeth (ETT) compared to controls without HGFP. The review protocol was registered on the OSF registries.

Methods

Literature searches were conducted in MEDLINE/ PubMed, Scopus, Web of Science, Embase, Google Scholar, and ProQuest for all relevant studies published up to Feb 2022. All in vitro studies that assessed the influence of HGFPs on fracture strength and fracture pattern of ETT whether MOD or MO or DO cavities were considered eligible. Review Manager (RevMan) was used for the meta-analysis. Subgroup and funnel plot analyses were also performed. Quality assessment was conducted by two independent reviewers.

Results

A total of 12 articles met the inclusion criteria, and 10 studies underwent quantitative evaluation. The pooled effect showed that fracture resistance of molar teeth restored with HGFP was significantly higher than teeth without HGFP (SMD: 1.61, 95% CI: 0.14, 3.09, p = 0.03), whereas marginally significant for premolars (SMD: 1.36, 95% CI: -0.00, 2.73, p = 0.05). Regarding fracture patterns, the presence of a HGFP significantly increased the occurrence of restorable fracture patterns for premolars (OR: 4.15, 95% CI: 1.60, 10.82, p = 0.004) compared to controls, whereas the difference was not significant for molars (OR: 1.09, 95% CI: 0.43, 2.77, p = 0.85). Moderate risk of bias was identified in 9/12 studies; one study showed high risk of bias and two studies showed low risk of bias.

Conclusion

Within the limitations of this study, there is evidence from in vitro studies that the use of HGFP increases the fracture resistance of the ETT when compared to teeth without HGFP and also reduces the occurrence of non-restorable fractures for premolars. However, a well-conducted in vitro and a prospective clinical studies are warranted to validate this finding.

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Pathogen‐agnostic immune biomarkers that predict infection after solid organ transplantation

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Pathogen-agnostic immune biomarkers that predict infection after solid organ transplantation


Abstract

Solid organ transplant recipients (SOTRs) remain at high risk for infection throughout their post-transplant course. Dosing of immunosuppressive medications, strategies that prevent infection, and choice of empiric antimicrobial treatment could be optimized by a better understanding of an individual patient's risk for infectious complications. Diagnostic tests that qualitatively or quantitatively measure the function of the immune system and/or its response to infection may be useful for individualized management decisions. Numerous studies have identified an association between infectious outcomes after solid organ transplantation (SOT) and the results of a variety of non-pathogen-specific or "pathogen-agnostic" immune monitoring tests. These biomarkers include humoral immune markers, functional or quantitative assessments of cellular immunity, transcriptomic-based diagnostics, and replication of viruses within the human virome, which have been used to predict or diagnose a v ariety of different infectious diseases complicating SOT. In this narrative review, we discuss several host-derived immune biomarkers that show promise for either predicting or diagnosing infection among SOTRs. However, additional studies are needed to determine the optimal use of immune response testing. Whether immune biomarkers contribute added benefits to current standard clinical care has not yet been determined. Testing must be validated across a range of clinical scenarios, including surveillance to predict infection risk and diagnosis of active infection at various time points post transplant.

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Exposure Characterization of Wood Dust Particulate, Endotoxins, and (1–3)-β-d-Glucans, and Their Determinants in Mozambiquan Wood Processing Workers

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Abstract
Objectives
Dust generated from wood processing comprises a heterogeneous mixture of inorganic and organic particles, including wood fragments, microorganisms, endotoxins, (1–3)-β-d-glucans, and allergens. This study characterized exposure to wood dust and its determinants in the Mozambiquan wood processing industry.
Methods
A total of 124 personal inhalable samples, collected from a stratified random sample of 30 workers, were analysed for dust particulate, endotoxins, and (1–3)-β-d-glucans. Mixed-effects models were developed to investigate significant exposure determinants.
Results
The geometric mean (GM) inhalable dust particulate concentrations were 3.29 mg m−3, 98 endotoxin units (EU) m−3, and 123 ng m−3 for (1–3)-β-d-glucans. Significant predictors for higher particulate levels included machinery (GMR = 1.93), sawing (GMR = 2.80), carpentry (GMR = 2.77), or painting (GMR = 3.03) tasks. Lebombo-ironwood species was associated with higher dust particulate levels (GMR = 1.97). Determinants of endotoxin concentrations included working with dry wood and damp cleaning methods, which were associated with lower levels. Working in closed buildings (GMR = 3.10) and dry sweeping methods were associated with higher (1–3)-β-d-glucan concentrations (GMR = 1.99).
Conclusions
Work tasks in certain exposure groups (machinery, sawing, carpentry, painting), processing certain wood species (Lebombo-ironwood) and working in closed buildings were associated with higher exposures, whilst using dry wood and damp cleaning practices reduced exposure levels.
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Perio‐prosthodontic pontic site management, part I: Pontic designs and their current applications

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Abstract

Objective

Emulating natural dentition with dental implant restorations is challenging, increasing its complexity when a pontic area must be restored. Many different methods have been described to solve this problem. The pontic designs which have been proposed have specific indications and may require additional treatments, including soft tissue augmentation procedures, to increase the possibility of an esthetically pleasing and biologically tolerable outcome. Proper conditioning of the soft tissues during the interim restoration stage and adequate communication with the laboratory are also critical factors to a successful outcome. This article describes the different approaches to restoring pontic sites with different degrees of complexity, their clinical indications, and limitations viewed from a perio-prosthodontic approach.

Clinical Considerations

Different clinical scenarios for pontic sites require different approaches. Missing hard and soft tissues can be replaced by surgical or prosthetic means. Understanding the clinical indications and implications of the different pontic designs allows the clinician to make good decisions when planning and treating patients that require replacement of pontic spaces leading to more successful outcomes.

Conclusions

Different pontic designs have specific indications as well as biologic and esthetic prognoses. Selection of a good design, proper modifications during the provisionalization stage, and adequate communication with the dental laboratory will lead to higher chances of esthetic and biological success.

Clinical Significance

The proper pontic design allows for esthetically pleasing pontic sites which emulate natural emergence from the soft tissues while promoting biological stability.

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