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Κυριακή 2 Οκτωβρίου 2022

Molecular landscapes of longitudinal NF2/22q and non‐NF2/22q meningiomas show different life histories

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Abstract

Recurrence is a major complication of some meningiomas. Although there were many studies on biomarkers associated with higher grades or increased aggressiveness, few studies specifically examined longitudinal samples of primary meningiomas and recurrences from the same patients for molecular life history. We studied 99 primary and recurrent meningiomas from 42 patients by FISH for 22q, 1q, 1p, 3p, 5q, 6q, 10p, 10q, 14q, 18q, CDKN2A/B homozygous deletion, ALT (Alternative Lengthening of Telomere), TERT re-arrangement, targeted sequencing and TERTp sequencing. Although NF2 mutation and 22q were well known to be aetiological events in meningiomas, we found that in these paired meningiomas, combining the two events resulted in an NF2/22q group (57 tumors from 25 patients) which were almost mutually exclusive with those cases without these two changes (42 tumors from 17 patients) for NF2/22q. No other molecular changes were totally unique to NF2/22q or non-NF2/22q tumors. For molecular evolution, NF2/22q meningiomas had higher cytogenetic abnormalities than non-NF2/22q meningiomas (p = 0.003). Most of the cytogenetic changes in NF2/22q meningiomas were present from the outset whereas for non-NF2/22q meningiomas, cytogenetic events were uncommon in the primary tumors and most were acquired in recurrences. For non-NF2/22q tumors, CDKN2A/B homozygous deletion, 1q gain, 18p loss, 3p loss, and ALT were preferentially found in recurrences. Mutations were largely conserved between primary and recurrent tumors. Phylogenetic trees showed 11/11 patients with multiple recurrent tumors had a conserved evolutionary pattern. We conclude that for molecular life history, NF2 and 22q should be regarded as a group. NF2/22q recurring meningiomas showed more cytogenetic abnormalities in the primary tumors, whereas non-NF2/22q meningiomas showed C DKN2A/B deletion and other cytogenetic abnormalities and ALT at recurrences. Although chromosome 1p loss is a known poor prognostic marker in meningiomas, it was also associated with a shorter TBR (time between resection) in this cohort (p = 0.002).

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Genetic Polymorphism in the Tumor Necrosis Factor Alpha gene (G‐308A) is associated with Persistent Apical Periodontitis in Brazilians

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Abstract

Aim

To investigate if there was an association between genetic polymorphisms in TNF-⍺ and its receptors TNFRSF1A and TNFRSF1B with persistent apical periodontitis (PAP) in Brazilian subjects.

Methodology

Patients who had pulpal necrosis and apical periodontitis installed at the time of treatment, with at least one-year of follow-up after non-surgical root canal treatment were recalled. 378 subjects were included, 150 subjects with signs/symptoms of PAP and 228 subjects with root canal–treated teeth exhibiting healthy perirradicular tissues (healed). Genomic DNA was extracted from saliva and used for TNF-⍺ (rs1800629), TNFRSF1A (rs1800693) and TNFRSF1B (rs1061622) genotyping by real-time PCR. Genotypes and alleles frequencies were evaluated by c2 or Fisher's exact tests and odds ratio were implemented (𝛂= 5%).

Results

The genetic polymorphism in TNF-α (rs1800629) was associated as a protective factor for the development of PAP (p<0.05), once subjects who presented at least one allele A (AA+AG X GG), had a higher chance to lesion repair (p<0.05). The polymorphisms rs1800693 and rs1061622 in TNF receptors (TNFRSF1A and TNFRSF1B respectively) were not associated with the development of PAP (p>0.05).

Conclusions

The observed results demonstrate that polymorphism in TNF-α but not in its receptors is associated with PAP.

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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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Controlling Nutritional Status (CONUT) score is a prognostic marker for laryngeal cancer patients with curative resection

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Abstract

Background

To investigate the prognostic value of pre-treatment Controlling Nutritional Status (CONUT) score in laryngeal cancer.

Methods

Preoperative CONUT score was retrospectively calculated in 154 laryngeal cancer patients who underwent curative resection in our hospital from 2013 to 2016. The associations of CONUT with clinicopathological factors and survival were evaluated. The efficacy of CONUT score to predict prognosis was evaluated.

Results

The CONUT score was associated with body mass index (p = 0.033), neutrophil (p = 0.011), tumor size (p = 0.017), pTNM stage (p = 0.001), adjuvant radiotherapy (p < 0.001), negative pathologic factors (p < 0.001), and larynx preservation (p < 0.001). Patients with a higher CONUT score had worse overall survival (hazard ratio: 1.94, 95% confidence interval [CI]: 1.13–3.72, p = 0.039) and disease-free survival (hazard ratio: 2.16, 95% CI: 1.19–3.90, p = 0.011). The area under the curve of CONUT score (0.728) was higher than Preoperative Nutritional Index (0.72), platelet-to-lymphocyte ratio (0.675), and neutrophil-to-lymphocyte ratio (0.687).

Conclusion

The CONUT score can be useful for predicting survival in laryngeal cancer patients after curative resection.

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Risk of adverse neonatal outcomes among pregnant women with disabilities

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Abstract
Background
To compare risk of neonatal morbidities between women with and without documented disability and to evaluate mediation of these associations by pre-term birth and caesarean delivery.
Methods
Using data from the Consortium on Safe Labor (2002–2008; n = 223 385), we evaluated risk of 22 neonatal outcomes among singleton deliveries using ICD-9 codes to define physical (n = 1733), sensory (n = 250) and intellectual disability (n = 91). Adjusted relative risk (aRR) was estimated for each outcome among each category of disability, and among women with any disability using Poisson regression models with robust variance. Causal mediation methods evaluated pre-term birth and caesarean delivery as mediators.
Results
Compared with no disabili ty, neonates of women with any disability had higher risk of nearly all neonatal outcomes, including pre-term birth (aRR = 1.77; 95% CI 1.62–1.94), small for gestational age (SGA) (aRR = 1.25; CI 1.11–1.41), neonatal intensive care unit (NICU) admission (aRR = 1.70; CI 1.54–1.87), seizures (aRR = 2.81; CI 1.54–5.14), cardiomyopathy (aRR = 4.92; CI 1.15–20.95), respiratory morbidities (aRR ranged from 1.33–2.08) and death (aRR = 2.31; CI 1.38–3.87). Women with disabilities were more likely to have a maternal indication for pre-term delivery, including pre-pregnancy diabetes (aRR = 3.80; CI 2.84–5.08), chronic hypertension (aRR = 1.46; CI 0.95–2.25) and severe pre-eclampsia/eclampsia (aRR = 1.47; CI 1.19–1.81). Increased risk varied but was generally consistent across all disability categories. Most outcomes were partially mediated by pre-term birth, except SGA, and heightened risk remained for NICU admissions, respiratory distre ss syndrome, anaemia and a composite of any adverse outcome (aRR = 1.21; CI 1.10–1.32).
Conclusion
Neonates of women with disabilities were at higher risk of a broad range of adverse neonatal outcomes, including death. Risks were not fully explained by pre-term birth.
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Transmission of Carbapenem-resistant Klebsiella pneumoniae in US hospitals

alexandrossfakianakis shared this article with you from Inoreader

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ABSTRACT
Background
Carbapenem-resistant Klebsiella pneumoniae (CRKp) is the most prevalent carbapenem-resistant Enterobacterales in the United States. We evaluated clustering of CRKp in hospitalized patients in US hospitals.
Methods
From April 2016 to August 2017, 350 patients with clonal group 258 were included as part of the Consortium on Re sistance Against Carbapenems in Klebsiella and other Enterobacteriaceae (CRACKLE-2), a prospective, multicenter, cohort study. A maximum-likelihood tree was constructed using RAxML. Static clusters shared ≤21 single nucleotide polymorphisms (SNP) and a most recent common ancestor. Dynamic clusters incorporated SNP distance, culture timing, and rates of SNP accumulation and transmission using the R program TransCluster.
Results
Most patients were admitted from home (n = 150, 43%) or a long-term care facility (n = 115, 33%). Urine (n = 149, 43%) was the most common site of isolation. In total, 55 static and 47 dynamics clusters were identified involving 210/350 (60%) and 194/350 (55%) patients, respectively. About half of static clusters were identical to dynamic clusters. Static clusters consisted of 33 (60%) intra-system and 22 (40%) inter-system clusters. Dynamic clusters consiste d of 32 (68%) intra-system and 15 (32%) inter-system clusters and had fewer SNP differences compared to static clusters (8 versus 9, P= 0.045, 95% CI: [-4, 0]). Dynamic inter-system clusters contained more patients than dynamic intra-system clusters (median [IQR]: 4 [2, 7] vs 2 [2, 2], P= 0.007, 95% CI: [-3, 0]).
Conclusions
Widespread intra-system and inter-system transmission of CRKp was identified in hospitalized US patients. Employing different methods for assessing genetic similarity resulted in only minor differences in interpretation.
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Τετάρτη 28 Σεπτεμβρίου 2022

The effect of adjuvant radiotherapy on clinical outcomes in early major salivary gland cancer

alexandrossfakianakis shared this article with you from Inoreader

Abstract

Background

This study investigated the effects of adjuvant radiotherapy on outcomes in early-stage major salivary gland cancers.

Methods

A total of 655 patients were identified, including 355 (54.2%) received adjuvant radiotherapy and 300 (45.8%) had surgery alone. The effect of adjuvant radiotherapy on 5-year locoregional recurrence and disease-specific survival (DSS) was calculated using the Kaplan–Meier method, Wilcoxon rank sum test, and Cox proportional hazards model.

Results

There were no significant differences in locoregional recurrence and DSS between patients receiving adjuvant radiotherapy and those not in both univariate and multivariable analysis. Although patients with positive margin status had a higher locoregional recurrence and those with moderate/poor differentiation had a worse DSS, stratified analysis still indicated there were no protective effects from the use of adjuvant radiotherapy.

Conclusions

The use of adjuvant radiation therapy was not associated with improved locoregional recurrence and DSS, even for those with high-risk histopathological factors.

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Pterygoid muscle activity in speech: a preliminary investigation

alexandrossfakianakis shared this article with you from Inoreader

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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Τρίτη 27 Σεπτεμβρίου 2022

Tracheostomy decreases continuous analgesia and sedation requirements

alexandrossfakianakis shared this article with you from Inoreader
imageBACKGROUND The goals of sedation in the critically ill surgical patient are to minimize pain, anxiety, and agitation without hindering cardiopulmonary function. One potential benefit of tracheostomy during endotracheal intubation is the reduction of sedation and analgesia; however, there are little data to support this supposition. We hypothesized that patients undergoing tracheostomy would have a rapid reduction in sedation and analgesia following tracheostomy. METHODS A retrospective review of tracheostomies performed at a single Level I trauma center from January 2013 to June 2018 was completed. An evaluation of Glasgow Coma Scale, Richmond Agitation-Sedation Scale, and Confusion Assessment Method for the intensive care unit 72 hours pretracheostomy to 72 hours posttracheostomy was performed. The total daily dose of sedation, anxiolytic, and analgesic medications administered were recorded. Mixed-effects models were used to evaluate longitudinal drug does over time (hours). RESULTS Four hundred sixty-eight patients included for analysis with a mean age of 58.8 ± 18.3 years. There was a significant decrease in propofol and fentanyl utilization from 24 hours pretracheostomy to 24 hours posttracheostomy in both dose and number of patients receiving these continuous intravenous medications. Similarly, total morphine milligram equivalents (MME) use and continuous midazolam significantly decreased from 24 hours pretracheostomy to 24 hours posttracheostomy. By contrast, intermittent enteral quetiapine and methadone administration increased after tracheostomy. Importantly, Richmond Agitation-Sedation Scale, Glasgow Coma Scale, and Confusion Assessment Method scoring were also significantly improved as early as 24 hours posttracheostomy. Total MME use was significantly elevated in patients younger than 65 years and in male patients pretracheostomy compared with female patients. Patients admitted to the medical intensive care unit had significantly higher MME use compar ed with those in the surgical intensive care unit pretracheostomy. CONCLUSION Tracheostomy allows for a rapid and significant reduction in intravenous sedation and analgesia medication utilization. Posttracheostomy sedation can transition to intermittent enteral medications, potentially contributing to the observed improvements in postoperative mental status and agitation. LEVEL OF EVIDENCE Therapeutic/Care Management; Level III.
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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.

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