Πέμπτη 29 Σεπτεμβρίου 2022

The French FRACTURE database: A way to improve knowledge on management of children with very rare tumors

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Abstract

Introduction

Very rare pediatric tumors (VRTs), defined by an annual incidence ≤2 per million inhabitants, represent a heterogeneous group of cancers. Due to their extremely low incidence, knowledge on these tumors is scant. Since 2012, the French Very Rare Tumors Committee (FRACTURE) database has recorded clinical data about VRTs in France. This study aims: (a) to describe the tumors registered in the FRACTURE database; and (b) to compare these data with those registered in the French National Registry of Childhood Cancer (RNCE).

Methods

Data recorded in the FRACTURE database between January 1, 2012 and December 31, 2018 were analyzed. In addition, these data were compared with those of the RNCE database between 2012 and 2015 to evaluate the completeness of the documentation and understand any discrepancies.

Results

A total of 477 patients with VRTs were registered in the FRACTURE database, representing 97 histological types. Of the 14 most common tumors registered in the RNCE (772 patients), only 19% were also registered in the FRACTURE database. Total 39% of children and adolescent VRTs registered in the RNCE and/or FRACTURE database (323 of a total of 828 patients) were not treated in or linked to a specialized pediatric oncology unit.

Conclusion

VRTs represent many different heterogenous entities, which nevertheless account for 10% of all pediatric cancers diagnosed each year. Sustainability in the collection of these rare tumor cases is therefore important, and a regular systematic collaboration between the FRACTURE database and the RNCE register helps to provide a more exhaustive picture of these VRTs and allow research completeness for some peculiar groups of patients.

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Τετάρτη 28 Σεπτεμβρίου 2022

Evaluation of an Opt-Out Protocol for Antibiotic De-escalation in Patients with Suspected Sepsis: a multicenter randomized controlled trial

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Abstract
Background
Sepsis guidelines recommend daily review to de-escalate or stop antibiotics in appropriate patients. This randomized controlled trial evaluated an opt-out protocol to decrease unnecessary antibiotics in patients with suspected sepsis.
Methods
We evaluated non-ICU adults on broad-spectrum antibiotics despite negative blood cultures at ten U.S. hospitals from September 2018 through May 2020. A 23-item safety check excluded patients with ongoing signs of systemic infection, concerning or inadequate microbiologic data, or high-risk conditions. Eligible patients were randomized to the opt-out protocol vs. usual care. The primary outcome was 30-day post-enrollment antibacterial days of therapy (DOT). Clinicians caring for intervention patients were contacted to encourage antibiotic discontinuation using opt-out language. If antibiotics were continued, clinicians discussed rationale for continuing antibiotics and de-escalation plans. To evaluate those with zero post-enrollment DOT, hurdle models provided two measures: 1) the odds ratio of antibiotic continuation and 2) ratio of mean DOT among those who continued antibiotics.
Results
Among 9606 patients screened, 767 (8%) were enrolled. Intervention patients had 32% lower odds of antibiotic continuation (79% vs. 84%, OR 0.68, 95% confidence interval (CI) [0.47, 0.98]). DOT among those who continued antibiotics were similar (ratio of means 1.06, 95% CI [0.88-1.26]). Few er intervention patients were exposed to extended-spectrum antibiotics (36% v. 44%. Common reasons for continuing antibiotics were treatment of localized infection (76%) and belief that stopping antibiotics was unsafe (31%). Thirty-day safety events were similar.
Conclusions
An antibiotic opt-out protocol targeting patients with suspected sepsis resulted in more antibiotic discontinuations, similar DOT when antibiotics were continued, and no evidence of harm.
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Prolonged neutropenia is a risk of oral adverse events-related sepsis but is not associated with prognosis of tooth extraction in hematopoietic stem cell transplant recipients: a retrospective study

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Publication date: Available online 27 September 2022

Source: Journal of Oral and Maxillofacial Surgery, Medicine, and Pathology

Author(s): Yasuyuki Shimada, Yuki Shiko, Akira Hangaishi, Yohei Kawasaki, Yutaka Maruoka

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Reconstruction of the Obliterated Eustachian Tube: A Pilot Case Series

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Reconstruction of the Obliterated Eustachian Tube: A Pilot Case Series

Complete occlusion of the cartilaginous ET can be associated with intractable mucoid effusion; endoscopic examination should be considered in such cases. In this pilot study, ET reconstruction was done and found to be a safe and possibly effective procedure in patients with total obliteration of the ET from various etiologies.


Objective

To investigate the safety and early efficacy of a procedure for reconstruction of the obliterated Eustachian tube (ET).

Study Design

Retrospective case series.

Methods

Patients with total obliteration of the cartilaginous ET, with intractable mucoid effusion causing repeated occlusion of tympanostomy tubes were included. Patients underwent endoscopic transnasal/transoral reconstruction of the obliterated ET using transtympanic illuminated guidewire guidance. A temporary stent (angiocatheter filled with bonewax) was placed to maintain patency while healing. In four cases an additional steroid-eluting propel stent was placed in the ET orifice. Main outcome measures were otomicroscopy results, absence of middle ear effusion, and nasopharyngoscopy showing patency of the ET orifice.

Results

Nine ETs (seven patients), ages 17–68 years (mean 37.9) underwent ET reconstruction. Follow-up ranged from 4 to 56 months (mean 30.9 months). 89% of operated ears had no effusion at last follow-up. Two patients (three Eustachian tubes) underwent successful reoperation. There were no complications directly related to the procedure. Etiologies of obliteration included scarring after sinus surgery, obstruction after maxillo-mandibular advancement surgery (two patients), bullous pemphigus, gunshot trauma, and previous patulous obliteration (two patients).

Conclusions

Complete occlusion of the cartilaginous ET can be associated with intractable mucoid effusion; endoscopic examination should be considered in such cases. In this pilot study, ET reconstruction was found to be a safe and possibly effective procedure in patients with total obliteration of the ET from various etiologies. Larger studies with long term follow up are indicated.

Level of Evidence

4 Laryngoscope, 2022

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Bone characteristics in condylar hyperplasia of the temporomandibular joint: a microcomputed tomography, histology, and Raman microspectrometry study

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Unilateral condylar hyperplasia (UCH) of the temporomandibular joint is a progressive deformation of the mandibular condyle of unknown origin. UCH is characterized by excessive growth of the condylar head and neck, leading to an increase in size and volume. The aim of this study was to investigate the characteristics of the bone in patients with UCH using microcomputed tomography (micro-CT), histology, and Raman microspectroscopy. The mandibular condyles of six patients with UCH were analysed using micro-CT, histology, and Raman microspectrometry and imaging, and the results were compared with those obtained for a normal control subject. (Source: International Journal of Oral and Maxillofacial Surgery)
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Pterygoid muscle activity in speech: a preliminary investigation

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Abstract

Background

Speaking depends on refined control of jaw opening and closing movements. The medial pterygoid muscle (MPT), involved in jaw closing, and the lateral pterygoid muscle (LPT), involved in jaw opening, are two key mandibular muscles in mastication and are likely to be recruited for controlled movements in speech.

Objectives

Three hypotheses were investigated, that during speech the MPT and LPT: (1) are both active, (2) but exhibit different patterns of activity, (3) which fluctuate with the vowels and consonants in speech.

Methods

Intramuscular EMG recordings were made from the right inferior head of the LPT and/or the right MPT in five participants during production of 40 target nonsense words (NWs) consisting of three syllables in the form /V1 C 1 V 2 C2ə/ (V = vowel; C = consonant; ə = unstressed, reduced vowel), spoken by each participant 10 times per NW; analysis focussed on the target syllable, C 1 V 2 .

Results

Both MPT and LPT exhibited robust increases in EMG activity during utterance of most NWs, relative to rest. Peak LPT activation was time-locked to the final part of the target consonant (C1) interval when the jaw begins opening for the target vowel (V2), whereas peak MPT activation occurred around the temporal midpoint of V2, when the jaw begins closing for C2. EMG amplitude peaks differed in magnitude between "high" vowels, i.e., for which the tongue/jaw are high (e.g., in S EE K), and "low" vowels, i.e., for which the tongue/jaw are low (e.g., in S O CK).

Conclusion

These novel findings suggest a key role for the LPT and MPT in the fine control of speech production. They imply that speech may impose major synergistic demands on the activities of the MPT and the LPT, and thereby provide insights into the possible interactions between speech activities and orofacial activities (e.g. mastication) and conditions (e.g. Temporomandibular Disorders) that involve the masticatory muscles.

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Evaluation and management of paediatric vertigo

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imagePurpose of review This review summarizes the most current information on cause, evaluation and treatment of dizziness in children. Recent findings There has been an increased understanding of the multifactorial cause of dizziness in the paediatric population. Quantitative vestibular testing is increasingly used and valuable as a diagnostic adjunct. Vestibular rehabilitation, migraine hygiene, psychological therapies, pharmaceuticals and/or surgery can be used as well tolerated and effective treatments for vertigo in children and adolescents when tailored to cause. Summary Paediatric vertigo can be effectively evaluated through careful history taking and physical examination along with adjunctive tests, such as vestibular testing and audiometry, when appropriate. Options for treatment of vestibular disorders in children and adolescents have greatly expanded in recent years allowing for the effective management of nearly all cases of paediatric vertigo, though a multimodal and/or multidisciplinary approach is often needed.
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Τρίτη 27 Σεπτεμβρίου 2022

A novel animal model of primary blast lung injury and its pathological changes in mice

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imageBACKGROUND Primary blast lung injury (PBLI) is a major cause of death in military conflict and terrorist attacks on civilian populations. However, the mechanisms of PBLI are not well understood, and a standardized animal model is urgently needed. This study aimed to establish an animal model of PBLI for laboratory study. METHODS The animal model of PBLI was established using a self-made mini shock tube simulation device. In brief, mice were randomly divided into two groups: the control group and the model group, the model group were suffered 0.5 bar shock pressures. Mice were sacrificed at 2 hours, 4 hours, 6 hours, 12 hours, and 24 hours after injury. Lung tissue gross observation, hematoxylin and eosin staining and lung pathology scoring were performed to evaluated lung tissue damage. Evans blue dye leakage and bronchoalveolar lavage fluid examination were performed to evaluated pulmonary edema. The relative expression levels of inflammation factors were measured by real-time quantitative polymerase chain reaction and Western blotting analysis. The release of neutrophil extracellular traps was observed by immunofluorescence stain. RESULTS In the model group, the gross observation and hematoxylin and eosin staining assay showed the inflammatory cell infiltration, intra-alveolar hemorrhage, and damaged lung tissue structure. The Evans blue dye and bronchoalveolar lavage fluid examination revealed that the lung tissue permeability and edema was significantly increased after injury. Real-time quantitative polymerase chain reaction and Western blotting assays showed that IL-1β, IL-6, TNF-α were upregulated in the model group. Immunofluorescence assay showed that the level of neutrophil extracellular traps in the lung tissue increased significantly in the model group. CONCLUSION The self-made mini shock tube simulation device can be used to establish the animal model of PBLI successfully. Pathological changes of PBLI mice were characterized by mechanical damage and inflammatory response in lung tissue.
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Hydrogen sulfide inhibits human T‐cell leukemia virus type‐1 (HTLV‐1) protein expression via regulation of ATG4B

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Abstract

Hydrogen sulfide(H2S)is a redox gasotransmitter. It has been shown that H2S has a key role in host antiviral defense by inhibiting interleukin (IL)-6 production and S-sulfhydrating Keap1 lead to Nrf2/ARE pathway activation. However, it is yet unclear whether H2S can play an antiviral role by regulating autophagy. In this research, we found that exogenous H2S decreased the expression of HTLV-1 protein and HTLV-1 induced autophagosomes accumulation. Transmission electron microscope assays indicated that autophagosomes accumulation decreased after H2S administration. HTLV-1-transformed T-cell lines had a high level of CSE (H2S endogenous enzyme) which could be induced in Hela by HTLV-1 infection. Immunoblot demonstrated that overexpression of CSE inhibited HTLV-1 protein expression and autophagy. And we got the opposite after CSE knockdown. Meanwhile, H2S could not restrain the aut ophagy when ATG4B had a mutant at its site of 89. In a word, these results suggested that H2S modulated HTLV-1 protein expression via ATG4B. Therefore, our findings suggested a new mechanism by which H2S defended against virus infection.

This article is protected by copyright. All rights reserved.

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Long-Term Exposure to Oxidant Gases and Mortality: Effect Modification by PM2.5Transition Metals and Oxidative Potential

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Background: Populations are simultaneously exposed to outdoor concentrations of oxidant gases (i.e., O3 and NO2) and fine particulate air pollution (PM2.5). Since oxidative stress is thought to be an important mechanism explaining air pollution health effects, the adverse health impacts of oxidant gases may be greater in locations where PM2.5 is more capable of causing oxidative stress. Methods: We conducted a cohort study of 2 million adults in Canada between 2001-2016 living within 10-km of ground-level monitoring sites for outdoor PM2.5 components and oxidative potential. Ox exposures (i.e., the redox weighted average of O3 and NO2) were estimated using a combination of chemical transport models, land use regression models, and ground level data. Cox proportional hazards models were used to estimate associations between 3-year moving average Ox and mortality outcomes across strata of transition metals and sulfur in PM2.5 and three measures of PM2.5 oxidative potential adjusting for possible confounding factors. Results: Associations between Ox and mortality were consistently stronger in regions with elevated PM2.5 transition metal/sulfur content and oxidative potential. For example, each interquartile increase (6.27 ppb) in Ox was associated with a 14.9% (95% CI: 13.0, 16.9) increased risk of nonaccidental mortality in locations with glutathione-related oxidative potential (OPGSH) above the median whereas a 2.50% (95% CI: 0.600, 4.40) increase was observed in regions with OPGSH levels below the median (interaction p-value
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