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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

alexandrossfakianakis shared this article with you from Inoreader

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

alexandrossfakianakis shared this article with you from Inoreader
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

alexandrossfakianakis shared this article with you from Inoreader

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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Using Latent Profile Analysis to Identify Associations Between Gestational Chemical Mixtures and Child Neurodevelopment

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Background: Unsupervised machine learning techniques have become increasingly popular for studying associations between gestational exposure mixtures and human health. Latent profile analysis is one method that has not been fully explored. Methods: We estimated associations between gestational chemical mixtures and child neurodevelopment using latent profile analysis. Using data from the Maternal-Infant Research on Environmental Chemicals (MIREC) research platform, a longitudinal cohort of pregnant Canadian women and their children, we generated latent profiles from 27 gestational exposure biomarkers. We then examined the associations between these profiles and child Verbal IQ, Performance IQ, and Full-Scale IQ, measured with the Wechsler Preschool and Primary Scale of Intelligence (WPPSI-III). We validated our findings using k-means clustering. Results: Latent profile analysis detected five latent profiles of exposure: a reference profile containing 61% of the study participants, a high Mono-ethyl Phthalate (MEP) profile with moderately low persistent organic pollutants (POPs) containing 26%, a high POP profile containing 6%, a low POP profile containing 4%, and a smoking chemicals profile containing 3%. We observed negative associations between both the smoking chemicals and high MEP profiles and all IQ scores, and between the high POP profile and Full-Scale and Verbal IQ scores. We also found a positive association between the low POP profile and Full-Scale and Performance IQ scores. All associations had wide 95% confidence intervals. Conclusion: Latent profile analysis is a promising technique for identifying patterns of chemical exposure, and is worthy of further study for its use in examining complicated exposure mixtures. Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.
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Accounting for misclassification and selection bias in estimating effectiveness of self-managed medication abortion

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Background: Studies on the effectiveness of self-managed medication abortion may suffer from misclassification and selection bias due to self-reported outcomes and loss to follow-up. Monte Carlo sensitivity analysis can estimate self-managed abortion effectiveness accounting for these potential biases. Methods: We conducted a Monte Carlo sensitivity analysis based on data from the Studying Accompaniment model Feasibility and Effectiveness Study (the SAFE Study), to generate bias-adjusted estimates of effectiveness of self-managed abortion with accompaniment group support. Between July 2019 and April 2020, we enrolled a total of 1051 callers who contacted accompaniment groups in Argentina and Nigeria for self-managed abortion information; 961 took abortion medications and completed at least one follow-up. Using these data, we calculated measures of effectiveness adjusted for ineligibility, misclassification, and selection bias across 50,000 simulations with bias parameters drawn from pre-specified Beta distributions in R. Results: After accounting for potential influence of various sources of bias, bias-adjusted estimates of effectiveness were similar to observed estimates, conditional on chosen bias parameters: 92.68% (95% simulation interval: 87.80%, 95.74%) for mifepristone in combination with misoprostol (versus 93.7% in the observed data) and 98.47% (95% simulation interval: 96.79%, 99.39%) for misoprostol alone (versus 99.3% in the observed data). Conclusions: After adjustment for multiple potential sources of bias, estimates of self-managed medication abortion effectiveness remain high. Monte Carlo sensitivity analysis may be useful in studies measuring an epidemiologic proportion (i.e., effectiveness, prevalence, cumulative incidence), while accounting for possible selection or misclassification bias. Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.
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