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Κυριακή 31 Ιουλίου 2022

Longitudinal Immune Response to Three Doses of mRNA Vaccine Against COVID-19 in Pediatric Patients Receiving Chemotherapy for Cancer

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Abstract
Our study in 21 pediatric cancer patients demonstrates that three doses of SARS-CoV-2 mRNA vaccine (BioNTech/Pfizer) elicited both humoral and cellular immunity in most patients during chemotherapy. Immunity was stronger in children with solid tumors and during maintenance therapy compared to those with hematological malignancies or during intensive chemotherapy.
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Nutrition impact symptoms and the risk of malnutrition in people with Parkinson's disease: a cross‐sectional study

alexandrossfakianakis shared this article with you from Inoreader

Abstract

Background

People with Parkinson's disease (PD) often experience symptoms that affect their ability to eat. This may contribute to weight loss and increased risk of malnutrition.

Objective

Our aim was to quantify the extent of nutrition impact symptoms (NIS) in the population and a scoring system of NIS is incorporated in the tool used to identify malnutrition.

Methods

In this cross-sectional study members of the Norwegian Parkinson's Association, with any PD diagnosis and stage of illness, were invited to respond to an online 24-item questionnaire. Questions from two validated questionnaires, abridged patient-generated subjective global assessment (aPG-SGA) and Radboud Oral Motor Inventory for Parkinson's disease (ROMP), were adapted to an online format.

Results

The questionnaire was sent to 3047 members, of which 508 persons (17%) responded (61% men). In total, 59% were categorized as well-nourished, 34% at risk of malnutrition a nd 6.5% as malnourished. A quarter of all participants reported symptoms that affected food intake. The most frequent symptoms were constipation (14.2%) and dry mouth (13.4%). On average (SD), malnourished participants reported 3.4 (1.4) symptoms as opposed to 0.1 (0.3) per well-nourished participant. Malnourished participants had more swallowing problems than well-nourished, a mean total ROMP score of 15.5 (6.0) versus 9.0 (2.9) (p <0.001). As the number of points in the ROMP-score increased by one, the points in the aPG-SGA score increased with 37% (95% CI 0.309-0.428).

Conclusion

Risk of malnutrition was largely related to NIS, especially dysphagia in people with PD. Symptoms affecting food intake should be systematically mapped and treated in conjunction with PD to prevent malnutrition.

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A modified dentin infection model with Fluorescent Lipopolysaccharide and LPS sampling technique to compare XP‐Endo finisher and passive ultrasonic irrigation

alexandrossfakianakis shared this article with you from Inoreader

Abstract

Aim

The LPS-dentine-infection models and sampling techniques frequently used to evaluate LPS disinfection have limitations. In this study, a lipopolysaccharides-dentine-infection (LPS-dentine-infection) model was devised using fluorescent conjugate LPS. Secondly, a sampling technique using cryogenic grinding for intraradicular LPS analysis was evaluated. Thirdly, the effectiveness of the XP-endo Finisher (XP-EF) was compared with passive ultrasonic irrigation (PUI) in removing LPS from root canal system.

Methodology

Sixty-nine mandibular premolars was submitted to dentine pretreatment and inoculated with fluorescent LPS conjugate (Alexa Fluor® 594). Twenty-three teeth were analysed under confocal laser scanning microscopy (CLSM) to validate this modified LPS-dentine-infection model. Forty-six teeth were randomly divided into two experimental groups: XP-EF (n = 23) and PUI (n = 23). All teeth were instrumented with XP-endo shaper (XPS; FKG Dentaire, La Chaux-de-Fonds, Switzerland) and 2.5% NaOCl. The root canals were sampled with paper points before (s1) and after (s2) instrumentation and after supplemental treatment (s3) with XP-EF and PUI. After s3, all roots were cryogenically ground for intraradicular LPS analysis (s4). Limulus amebocyte lysate (LAL) assay was used for LPS quantification. The Friedman test was used for differences in LPS among four timepoints (s1, s2, s3, and s4). Dunn's test was used for pairwise testing of timepoints. The significance level wa s set at 5% (P < .05).

Results

Fluorescent LPS conjugate was detected in 100% of the samples under CLSM with a penetration depth of approximately 400 μm into dentine. Chemo-mechanical preparation using XPS files significantly reduced LPS levels (p < .05). Both the XPS and PUI improved the LPS disinfection (p < .05), with no difference between them (p > .05). LPS was recovered from all samples after cryogenic grinding. The residual amount of LPS detected using the cryogenically sampling technique at s4 was approximately 3 times greater than with the paper point sampling technique at s3.

Conclusion

This study established a modified LPS-dentine-infection model using fluorescent conjugate LPS, and validated a LPS sampling technique for using cryopulverization intraradicular LPS analysis. Moreover, both the XP-EF and PUI further improved LPS disinfection from the root canals, and the innovative XP-EF was as effective as PUI.

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Case volume regionalization and volume‐based outcome differences in cutaneous head and neck melanoma

alexandrossfakianakis shared this article with you from Inoreader

Abstract

Background

Hospital volume has emerged as a prognostic factor in oncology but is not currently known whether volume is associated with improved outcomes for cutaneous head and neck (HN) melanoma.

Methods

A total of 556 079 cutaneous melanoma cases reported by the 2004–2016 National Cancer Database were separated into two cohorts (HN and non-HN) and facilities within each cohort were classified by case volume. Analysis employed chi-square, analysis of variance, Kaplan–Meier, and Cox proportional hazards models.

Results

Only 41 facilities (3.1% of 1326) treating HN melanoma and 50 facilities (3.7% of 1344) treating non-HN melanoma were classified as high-volume facilities (HVFs). The estimated 5-year overall survival (OS) was 62.7% (standard error [SE]: 0.4%) for patients with HN at low-volume facilities (LVFs), 69.3% (SE: 0.4%) at IVFs, and 71.8% (SE 0.4%) at HVFs (p < 0.001). Differences in OS remained significant between HVFs versus LVFs after adjusting for confounders.

Conclusion

Volume is independently associated with OS and improved surgical outcomes for HN melanoma.

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Impact of a prognostic model for overall survival on the decision‐making process in a head and neck cancer multidisciplinary consultation meeting

alexandrossfakianakis shared this article with you from Inoreader

Abstract

Background

Multidisciplinary decision-making in head and neck cancer care is complex and requires a tradeoff between prolonging survival and optimizing quality of life. To support prognostication and decision-making in head and neck cancer care, an individualized prognostic model for overall survival (OncologIQ) is available.

Methods

By quantitative and qualitative research we have studied user value of OncologIQ and its impact on the decision-making process in a multidisciplinary consultation meeting.

Results

Healthcare professionals experienced added value upon using prognostic estimates of survival from OncologIQ in half (47.5%) of the measurements. Significant impact on the decision making process was seen when OncologIQ was used for older patients, patients having a WHO performance score ≥ 2, or high tumor stage.

Conclusions

The prognostic model OncologIQ enables patient-centered decision-making in a multidisciplinary consultation meeting and was mostly valued in complex patients.

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Eano-Euracan-Sno Guidelines on Circumscribed Astrocytic GLIOMAS, Glioneuronal and Neuronaltumors

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Abstract
In the new WHO 2021 Classification of CNS Tumors the chapter "Circumscribed astrocytic gliomas, glioneuronal and neuronal tumors" encompasses several different rare tumor entities, which occur more frequently in children, adolescents and young adults. The Task Force has reviewed the evidence of diagnostic and therapeutic interventions, which is low particularly for adult patients, and draw recommendations accordingly. Tumor diagnosis, based on WHO 2021, is primarily performed using conventional histological techniques; however, molecular workup is important for differential diagnosis, in particular DNA methylation profiling for the definitive classification of histologically unresolved cases. Molecular factors are increasingly of prognostic and predictive importance. MRI finding are non specific, but for some tumors are characteristic and suggestive. Gross total resection, when feasible, is the most important treatment in terms of prolonging survival and achieving long-term seizure control. Conformal radiotherapy should be considered in grade 3 and incompletely resected grade 2 tumors. In recurrent tumors reoperation and radiotherapy, including stereotactic radiotherapy, can be useful. Targeted therapies may be used in selected patients: BRAF and MEK inhibitors in pilocytic astrocytomas, pleomorphic xanthoastrocytomas, and gangliogliomas when BRAF altered, and mTOR inhibitor everolimus in subependymal giant cells astrocytomas .Sequencing to identify molecular targets is advocated for diagnostic clarification and to direct potential targeted therapies.
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Πέμπτη 28 Ιουλίου 2022

Facial nerve palsy: Narrative review on the importance of the eye and its assessment

alexandrossfakianakis shared this article with you from Inoreader

Abstract

New solutions are emerging that address specific facial regions in facial nerve palsy (FNP). However the most dreaded consequence of FNP is paralytic lagophthalmos threatening the eye. A way to prioritize these regions is thus required. A review of the literature is conduced to capture the current concepts in evaluating FNP. Overall, patients are assessed from three perspectives: from the clinician's perspective using validated clinician-based grading instruments, from patient's perspective based on FNP-specific patient-reported outcome measures, and from the perspective of the layperson. The existing tools however provide limited information regarding the relative importance of different regions of the face. The eye appears to be an area of great concern for the patient where most surgical therapies are directed at. Addressing ocular problems in FNP carry a high priority but this is not clearly reflected by the standard systems.

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STATIN USE MAY BE ASSOCIATED WITH A LOWER RISK OF INVASIVE ASPERGILLOSIS IN LUNG TRANSPLANT RECIPIENTS

alexandrossfakianakis shared this article with you from Inoreader
Abstract
Background
Statins are competitive inhibitors of HMG-CoA reductase that catalyses HMG-CoA conversion to mevalonate, a process involved in synthesizing cholesterol in humans and ergosterol in fungi. The effect of statin use on the risk of development of invasive aspergillosis (IA) in lung transplant recipients (LTRs) is not well documented.
Methods
This retrospective study included LTRs from 2010 to 2017 who were followed for one-year post-transplant. Proven or probable IA was diagnosed as per ISHLT criteria. We performed a multivariable Cox proportional hazards model of the association between IA and statin use (minimum of two weeks duration prior to IA), adjusting for other known IA risk factors.
Results
We identified 785 LTRs, 44% female, mean age 53 years old, the most common underlying disease being pulmonary fibrosis (23.8%). 451 LTRs (57%) received statins post-transplant, atorvastatin was the most commonly used statin (68%). The mean duration of statins post-transplant was 347 days (IQR: 305 to 346). 55 (7%) LTRs developed IA in the first-year post-transplant. Out of these 55 LTRs, 9 (16.3%) had received statin before developing IA. In multivariable analysis, statin use was independently associated with a lower risk of IA (p = 0.002, SHR 0.30, CI 95% 0.14-0.64). Statin use was also associated with a lower incidence of post-transplant Aspergillus colonization, 114 (34%) in the no statin group vs. 123 (27%) in the statin group (p = 0.038).
Conclusions
The use of statin for a minimum of two weeks during the first-year post-transplant was associated with a 70% risk reduction of IA in LTRs.
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Genetic predisposition & evolutionary traces of pediatric cancer risk: A prospective 5-year population-based genome sequencing study of children with CNS tumors

alexandrossfakianakis shared this article with you from Inoreader
Abstract
Background
The etiology of central nervous system (CNS) tumors in children is largely unknown and population-based studies of genetic predisposition are lacking.
Methods
In this prospective, population-based study, we performed germline whole-genome sequencing in 128 children with CNS tumors, supplemented by a systematic pedigree analysis covering 3,543 close relatives.
Results
Thirteen children (10%) harbored pathogenic variants in known cancer genes. These children were more likely to have medulloblastoma (OR 5.9, CI 1.6-21.2) and develop metasynchronous CNS tumors (p=0.01). Similar carrier frequencies were seen among children with low-grade glioma (12.8%) and high-grade tumors (12.2%). Next, considering the high mortality of childhood CNS tumors throughout most of human evolution, we explored known pediatric-onset cancer genes, showing that they are more evolutionarily constrained than genes associated with risk of adult-onset malignancies (p=5e-4) and all other genes (p=5e-17). Based on this observation, we expanded our analysis to 2 986 genes exhibiting high evolutionary constraint in 141 456 humans. This analysis identified eight directly causative loss-of-functions variants, and showed a dose-response association between degree of constraint and likelihood of pathogenicity - raising the question of the role of other highly constrained gene alterations detected.
Conclusions
∽10% of pediatric CNS tumors can be attributed to rare variants in known cancer genes. Genes associated with high risk of childhood cancer show evolutionary evidence of constraint.
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Τετάρτη 27 Ιουλίου 2022

Neuropsychological, behavioral, and quality‐of‐life outcomes in children and adolescents with sickle cell disease treated with nonmyeloablative matched sibling donor hematopoietic cell transplantation: A case series

alexandrossfakianakis shared this article with you from Inoreader

Abstract

Background/objectives

Despite advances in the treatment of sickle cell disease (SCD), cerebrovascular and cognitive insults can have lifelong consequences. Hematopoietic cell transplantation (HCT) is an established curative therapy, and recent studies have demonstrated efficacy with reduced toxicity nonmyeloablative (NMA) regimens, but little is known about neuropsychological outcomes. The objective of this study was to describe neuropsychological, behavioral, and quality-of-life outcomes with medical correlates in children with SCD who received an NMA matched sibling donor (MSD) HCT.

Design/methods

Retrospective cohort analysis of nine recipients with hemoglobin SS SCD who underwent MSD HCT using the National Institutes of Health (NIH) NMA protocol.

Results

Mean full-scale intellectual functioning (FSIQ) was average pre-HCT (FSIQ = 92.1, SD 9.0; n = 8) and 2 years post-HCT (mean FSIQ = 96.6; SD 11.1; N = 9). Neuropsychological functioning was largely average across all cognitive domains, and no pre/post-HCT differences were found to be statistically significant given the small sample size. However, effect sizes revealed moderate improvements in processing speed (Cohen's d = .72) and verbal memory (Cohen's d = .60) post-HCT, and declines in measures of attention (Cohen's d = −.54) and fine motor speed and dexterity (Cohen's d = −.94). Parents endorsed better quality of life (Cohen's d = .91), less impact of SCD on their family, and less worry about their child's future (Cohen's d = 1.44).

Conclusion

Neuropsychological functioning in a sample of children and adolescents treated uniformly with NMA MSD HCT remained stable or improved in most cognitive domains, and improvements in quality of life and family functioning were observed.

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