Alexandros G .Sfakianakis,ENT,Anapafeos 5 Agios Nikolaos Crete 72100 Greece,00302841026182

Πέμπτη 28 Απριλίου 2022

Single nucleotide polymorphisms as a predisposing factor for the development of apical periodontitis ‐ an umbrella review

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Abstract

Background

The interaction between heredity and different environmental factors in the modification of apical periodontitis (AP) susceptibility and prediction of its progression remain poorly elucidated.

Objectives

This umbrella review aimed to (i) analyse the available relevant systematic reviews in an attempt to determine the association between genotype and allelic distribution of different single nucleotide polymorphisms (SNPs) and the development of AP, (ii) report deficiencies and gaps in knowledge in this area, and (iii) present recommendations to conduct future clinical studies and systematic reviews.

Methods

A literature search was conducted using Clarivate Analytics' Web of Science, Scopus, PubMed, and Cochrane Database of Systematic Reviews, from inception to October 2021, with no language restrictions, including a grey literature search. Systematic reviews with/without meta-analysis evaluating genotype and allelic distribution of different SNPs between adult patients with/ without AP were included. All other type of studies were excluded. The methodological quality was assessed using the A MeaSurement Tool to Assess systematic Reviews (AMSTAR) - 2 tool. Two independent reviewers were involved in study selection, data extraction, and appraising the included reviews; disagreements were resolved by a third reviewer.

Results

The current study includes five systematic reviews. Three reviews performed meta-analysis. Three reviews were graded by AMSTAR 2 as 'critically low' quality, whereas other two were graded as 'low' and 'moderate' quality. Two reviews indicated that carriers of specific genotypes and alleles of tumour necrosis factor – alpha (TNF-α) -308 G>A and interleukin 1-beta (IL-1β) +3954 C/T gene polymorphisms are more susceptible to an acute and persistent form of AP. However, high heterogeneity was observed.

Discussion

The statistical heterogeneity within included systematic reviews was a consequence of clinical and methodological diversity amongst primary studies. Although some of included reviews suggested that carriers of specific genotype and/or allele of TNF-α -308 G>A and IL-1β +3954 C/T SNPs are more susceptible to AP, their conclusions should be interpreted with caution.

Conclusions

No candidate genes could be identified as a definitive genetic risk or protective factor for the development and progression of AP, and further high-quality genome-wide association studies are warranted.

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Airflow patterns in double occupancy patient rooms may contribute to roommate-to-roommate transmission of severe acute respiratory syndrome coronavirus 2

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Abstract
Background
Hospitalized patients are at risk to acquire severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) from roommates with unrecognized coronavirus disease 2019 (COVID-19). We hypothesized that airflow patterns might contribute to SARS-CoV-2 transmission in double occupancy patient rooms.
Methods
A device emitting condensed moisture was used to identify airflow patterns in double occupancy patient rooms. Simulations were conducted to assess transfer of fluorescent microspheres, 5% sodium chloride aerosol, and aerosolized bacteriophage MS2 between patient beds 3 meters apart and to assess the effectiveness of privacy curtains and portable air cleaners in reducing transfer.
Results
Air flowed from inlet vents in the center of the room to an outlet vent near the door, resulting in air currents flowing toward the bed adjacent to the outlet vent. Fluorescent microspheres (212-250 µm diameter), 5% sodium chlor ide aerosol, and aerosolized bacteriophage MS2 released from the inner bed were carried on air currents toward the bed adjacent to the outlet vent. Closing curtains between the patient beds reduced transfer of each of the particles. Operation of a portable air cleaner reduced aerosol transfer to the bed adjacent to the outlet vent but did not offer a benefit over closing the curtains alone, and in some situations resulted in an increase in aerosol exposure.
Conclusion
Airflow patterns in double occupancy patient rooms may contribute to risk for transmission of SARS-CoV-2 between roommates. Keeping curtains closed between beds may be beneficial in reducing risk.
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KDR genetic predictor of toxicities induced by sorafenib and regorafenib

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The Pharmacogenomics Journal, Published online: 28 April 2022; doi:10.1038/s41397-022-00279-3

KDR genetic predictor of toxicities induced by sorafenib and regorafenib
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Effect of Selective Carboplatin-Induced Inner Hair Cell Loss on Temporal Integration

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AbstractIntegration of acoustic information over time is essential for processing complex stimuli, such as speech, due to its continuous variability along the time domain. In both humans and animals, perception of acoustic stimuli is a function of both stimulus intensity and duration. For brief acoustic stimuli, as duration increases, thresholds decrease by approximately 3  dB for every doubling in duration until stimulus duration reaches 500 ms, a phenomenon known as temporal integration. Although hearing loss and damage to outer hair cells (OHC) have been shown to alter temporal integration in some studies, the role of cochlear inner hair cells (IHC) on temporal i ntegration is unknown. Because IHC transmit nearly all acoustic information to the central auditory system and are believed...
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Blinatumomab overcomes poor prognostic impact of measurable residual disease in pediatric high‐risk first relapse B‐cell precursor acute lymphoblastic leukemia

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Abstract

Background

Blinatumomab, a CD3/CD19 BiTE® (bispecific T cell engager) molecule, was superior to high-risk third course consolidation chemotherapy (HC3) in prolonging event-free survival (EFS) in children with high-risk first relapse B-cell precursor acute lymphoblastic leukemia (B-ALL). Here, we report results from a post hoc measurable residual disease (MRD) analysis of this phase 3 study (NCT02393859).

Procedure

Children >28 days and <18 years with high-risk first-relapse B-ALL in cytomorphological complete remission (M1 marrow, <5% blasts) or with M2 marrow (≥5% and <25% blasts) after induction and two cycles of high-risk consolidation chemotherapy (baseline) were enrolled in this trial. Patients received one cycle of blinatumomab (15 μg/m2/day, 4 weeks, continuous intravenous infusion) or HC3. The primary endpoint was EFS. In this post hoc analysis, patients with MRD <10–4 by PCR were grouped as having positive but not quantifiable (pbnq) or undetectable disease.

Results

A higher proportion of patients with MRD <10–4 had undetectable versus pbnq disease after blinatumomab (day 29) than after HC3 (p = 0.0367). Of the 22 patients with MRD ≥10–4 at baseline who achieved MRD remission after blinatumomab, 20 (91%) achieved MRD <10–4 remission by day 15. Patients treated with blinatumomab had improved EFS and overall survival compared with those treated with HC3 independent of end-of-induction or baseline (end-of-second consolidation) MRD levels.

Conclusions

Blinatumomab was more efficacious than HC3 regardless of MRD status before treatment. These data support the role of blinatumomab in inducing deep MRD remission, negating the poor prognostic value of MRD.

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Τετάρτη 27 Απριλίου 2022

Cell pyroptosis in picornavirus and its potential for treating viral infection

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Abstract

Cell pyroptosis has received increased attention due to the associations between innate immunity and disease, and it has become a major focal point recently due to in-depth studies of cancer. With increased research on pyroptosis, scientists have discovered that it has an essential role in viral infections, especially in the occurrence and development of some picornavirus infections. Many picornaviruses, including Coxsackievirus, a71 enterovirus, human rhinovirus, encephalomyocarditis virus, and foot-and-mouth disease virus induce pyroptosis to varying degrees. This review summarized the mechanisms by which these viruses induce cell pyroptosis, which can be an effective defense against pathogen infection. However, excessive inflammasome activation or pyroptosis also can damage the host's health or aggravate disease progression. Careful approaches that acknowledge this dual effect will aid in the exploration of picornavirus infections and the mechanisms that produce the inflammatory response. This information will promote the development of drugs that can inhibit cell pyroptosis and provide new avenues for future clinical treatment.

This article is protected by copyright. All rights reserved.

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Low Body Mass Index at Treatment Initiation and Rifampicin-Resistant Tuberculosis Treatment Outcomes: An Individual Participant Data Meta-Analysis

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Abstract
Background
The impact of low body-mass-index at treatment initiation on rifampicin-resistant tuberculosis treatment outcomes is uncertain. We evaluated the association between body-mass-index at rifampicin-resistant tuberculosis treatment initiation and end-of-treatment outcomes, and its modifying factors.
Methods
We did an individual participant data meta-analysis of adults ≥18 years with rifampicin-resistant tuberculosis whose body-mass-index was documented at treatment initiation. We compared odds of any unfavorable treatment outcome, mortality, or failure/recurrence between patients who were underweight (body-mass-index <18.5 kg/m2) and not underweight. Adjusted odds ratios and 95%CI were estimated using logistic regression, with matching on demographic, clinical, and treatment-related factors. We evaluated effect modification by HIV-infection and other variables using likelihood ratio tests. In secondary an alysis, we estimated cumulative incidence of mortality during treatment, stratified by HIV-infection.
Results
Overall, 5148 patients were included; 1702 (33%) were underweight at treatment initiation. The median (IQR) age was 37 years (29 to 47) and 455 (9%) were living with HIV. Compared to non-underweight patients, the adjusted odds ratio among underweight patients was 1.7 (95%CI 1.4-1.9) for any unfavorable outcome, 3.1 (2.4-3.9) for death, and 1.6 (1.2-2.0) for failure/recurrence. Significant effect modification was observed for WHO region where the participant was treated. Among patients without HIV, cumulative incidence of 24-month mortality 14.8% (95%CI 12.7%-17.3%) for underweight and 5.6% (4.5%-7.0%) for not underweight patients. Among patients living with HIV, corresponding values were 33.0% (25.6%-42.6%) and 20.9% (14.1%-27.6%).
Conclusions
Low body-mass-index at treatment initiation for rifampicin-resistant tuberculosis is associated with increased odds of unfavorable treatment outcome, particularly mortality.
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Cytokine profile and cholesterol levels in patients with Niemann-Pick type C disease presenting neurological symptoms: The in vivo effect of miglustat and the in vitro effect of N-acetylcysteine and Coenzyme Q10

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Publication date: Available online 27 April 2022

Source: Experimental Cell Research

Author(s): Tatiane G. Hammerschmidt, Bruna Donida, Jéssica L. Faverzani, Alana P. Moura, Bianca G. dos Reis, Andryele Z. Machado, Rejane G. Kessler, Fernanda M. Sebastião, Luiza S. Reinhardt, Dinara J. Moura, Carmen R. Vargas

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Factors Correlating with Survival Following Adjuvant or Definitive Radiosurgery for Large Brain Metastases

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Abstract
Background
We sought to identify variates correlating with overall survival (OS) in patients treated with surgery (S) plus adjuvant stereotactic radiosurgery (SRS) versus definitive SRS for large (>4cc) brain metastases (BrM).
Methods
We used univariate (UVA) and multivariate analyses (MVA) to identify survival correlates among eligible patients identified from a prospective registry and compared definitive SRS to S+ adjuvant SRS cohorts using propensity score-matched analysis (PSMA). Secondary outcomes were measured using the cumulative incidence (CI) method.
Results
We identified 364 patients; 127 and 237 were treated with S+SRS and definitive SRS, respectively. On UVA, SRS alone [HR1.73 (1.35,2.22) P<0.001), BrM quantity [HR 1.13 (1.06-1.22) (P<0.001)]; performance status (PS) [HR 2.78 (1.73-4.46) (P<0.001)]; extracranial disease (ECD) [HR 1.82 (1.37,2.40) (P<0.001)]; and receipt of systemic treatment after BrM therapy, [HR 0.58 (0.46-073) (P<0.001)] correlated with OS. On MVA, SRS alone [HR 1.81 (1.19,2.74) (P<0.0054)], SRS target volume [HR 1.03 (1.01,1.06) (P<0.0042)], and receipt of systemic treatment [HR 0.68 (0.50,0.93) (P<0.015)] correlated with OS. When PSMA was used to balance ECD, BrM quantity, PS, and SRS target volume, SRS alone remained correlated with worsened OS [HR 1.62 (1.20-2.19) (P=0.0015)]. CI of local failure requiring resection at 12 months was 3% versus 7% for S+SRS and SRS cohorts, respectively [(HR 2.04 (0.89-4.69) (P =0.091)]. CI of pachymeningeal failure at 12 months was 16% versus 0% for S+SRS and SRS.
Conclusion
SRS target volume, receipt of systemic therapies, and treatment with S+SRS instead of definitive SRS correlated with improved survival in patients with large BrM.
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The intrinsic and microenvironmental features of diffuse midline glioma; implications for the development of effective immunotherapeutic treatment strategies

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Abstract
Diffuse midline glioma (DMG), including those of the brainstem (diffuse intrinsic pontine glioma), are pediatric tumors of the central nervous system (CNS). Recognized as the most lethal of all childhood cancers, palliative radiotherapy remains the only proven treatment option, however, even for those that respond, survival is only temporarily extended. DMG harbor an immunologically 'cold' tumor microenvironment (TME) with few infiltrating immune cells. The mechanisms underpinning the cold TME are not well understood. Low expression levels of immune checkpoint proteins, including PD-1, PD-L1 and CTLA-4, are recurring features of DMG and likely contribute to the lack of response to immune checkpoint inhibitors (ICIs). The unique epigenetic signatures (including stem cell-like methylation patterns), a low tumor mutational burden, and recurring somatic mutations (H3K27M, TP53, ACVR1, MYC and PIK3CA), possibly play a role in the reduced efficacy of traditional immunotherapies. Therefore, to circumvent the lack of efficacy thus far seen for the use of ICIs, adoptive cell transfer (including chimeric antigen receptor T cells) and the use of oncolytic viruses, are currently being evaluated for the treatment of DMG. It remains an absolute imperative that we improve our understanding of DMG's intrinsic and TME features if patients are to realize the potential benefits offered by these sophisticated treatments. Herein, we summarize the limitations of immunotherapeutic approaches, highlight the emerging safety and clinical efficacy shown for sophisticated cell-based therapies, as well as the evolving knowledge underpinning the DMG-immune axis, to guide in the development of immunotherapies that we hope will improve outcomes.
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Tetrahedral framework nucleic acid carrying angiogenic peptide prevents bisphosphonate-related osteonecrosis of the jaw by promoting angiogenesis

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International Journal of Oral Science, Published online: 27 April 2022; doi:10.1038/s41368-022-00171-7

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Τρίτη 26 Απριλίου 2022

18F-FDG PET/CT Uptake in Acute Pontine Infarct Mimicking Intracranial Metastasis

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imageInfarcts are generally nonviable and are not avid on an 18F-FDG PET/CT. Here, we discuss a 53-year-old man who presented with chest pain and raised d-dimer. CT pulmonary angiogram was performed to exclude pulmonary embolism, which identified incidental lung nodules. 18F-FDG PET/CT was performed for the assessment of lung nodules, which showed incidental focal FDG uptake in the pons. This was concluded as an acute infarct on subsequent MR scan. This highlights the importance of not interpreting all focal FDG uptakes as malignant. In rare circumstances, false-positive benign causes should be considered, such as in this rare case of an acute pontine infarct.
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