Κυριακή 31 Ιουλίου 2022

Intra‐articular non‐steroidal anti‐inflammatory drugs may promote cartilage degeneration

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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

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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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Assessment of masticatory efficiency based on glucose concentration in orthodontic patients – a methodological study

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Abstract

Introduction

Treatment for malocclusion can cause discomfort and pain in the teeth and periodontium, which may impair masticatory efficiency. The glucose concentration method is widely used to assess masticatory efficiency for its convenience in the clinical situation, although its validity has not been shown.

Objective

The aims were to determine the validity of the glucose concentration method and investigate if this method can be applicable to orthodontic patients with braces.

Design

Sixteen healthy individuals (7 men, 9 women, and 26±5 years old) and 16 patients with malocclusions needing orthodontic treatment (5 men, 11 women, and 26±4 years old) participated. Glucose concentration was measured after 5-, 10-, and 15-s mastication of gummy jelly and compared to Hue values obtained from the color-changing gum method (reference method). In addition, all participants were asked to fill out the Oral Health Impact Profile questionnaire (OHIP) to assess differences in perception related to the mouth before and after the placement of braces.

Results

Glucose concentrations were strongly correlated to measures of the two-color chewing gum methods (R2=0.965). Both the glucose extraction and chewing gum hue value were the smallest for 5 s chewing cycles and increased as the number of chewing strokes increased for the 15 s chewing cycles. (Hue: R2 = 0.510, P < 0.001; glucose: R2 = 0.711, P < 0.001) Masticatory efficiency assessed by both methods was significantly lower in orthodontic patients compared to controls (P<0.05), even though it was not affected by bonding (P>0.09). In addition, OHIP scores in physical pain dimension and psychological disability were higher in orthodontic patients than in the control group (P<0.005).

Conclusion

Measurement of glucose concentration was confirmed as a reliable and convenient method for assessing masticatory efficiency. Furthermore, it appears that this method is applicable to patients with braces whose perception in the oral cavity could change.

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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

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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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Genomic Annotation and Molecular Evolution of Monkeypox Virus Outbreak in 2022

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ABSTRACT

Monkeypox virus (MPXV) has generally circulated in West and Central Africa since its emergence. Recently, sporadic MPXV infections in several non-endemic countries have attracted widespread attention. Here, we conducted a systematic analysis of the recent outbreak of MPXV-2022, including its genomic annotation and molecular evolution. The phylogenetic analysis indicated that the MPXV-2022 strains belong to the same lineage of the MPXV strain isolated in 2018. However, compared with the MPXV strain in 2018, in total 46 new consensus mutations were observed in the MPXV-2022 strains, including 24 non-synonymous mutations. By assigning mutations to 187 proteins encoded by the MPXV genome, we found that ten proteins in the monkeypox virus are more prone to mutation, including D2L-like, OPG023, OPG047, OPG071, OPG105, OPG109, A27L-like, OPG153, OPG188, and OPG210 proteins. In the MPXV-2022 strains, 4 and 3 nucleotide substitutions are observed in OPG105 and OPG210 , respectively. Overall, our studies illustrated the genome evolution of the ongoing MPXV outbreak and pointed out novel mutations as a reference for further studies.

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

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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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Menopausal hormone therapy and subclinical cardiovascular disease in women with and without HIV

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Abstract
Background
Estrogen-based hormone therapy (HT) may have beneficial cardiovascular effects when initiated in early menopause. This has not been examined in women with HIV who have heightened immune activation and cardiovascular risks.
Methods
Among 609 post-menopausal women (1,234 person-visits) in the Women's Interagency HIV Study, we examined the relationship of ever HT use (oral, patch, or vaginal) with subclinical atherosclerosis – carotid artery intima-media thickness (CIMT), distensibility, and plaque assessed via repeated B-mode ultrasound imaging (2004-2013). We also examined associations of HT with cross-sectional biomarkers of immune activation and D-dimer. Statistical models were adjusted for sociodemographic, behavioral, and cardiometabolic factors.
Results
Women (mean age = 51, 80% HIV+) who ever used HT at baseline were older, and more likely to be non-Hispanic White and report higher income, than never users. Women who ever used HT had 43% lower prevalence of plaque (prevalence ratio = 0.57; 95% CI = [0.40, 0.80]; p < 0.01), 2.51 µm less progression of CIMT per year (95% CI = [-4.60, -0.41]; p = 0.02), and marginally lower incidence of plaque over ∼7 years (risk ratio = 0.38; 95% CI = [0.14, 1.03]; p = 0.06), compared with never users, adjusting for covariates; ever HT use was not associated with distensibility. These findings were similar for women with and without HIV. Ever HT use was associated with lower serum D-dimer, but not with biomarkers of immune activation after covariate adjustment.
Conclusions
HT may confer a subclinical cardiovascular benefit in women with HIV. These results begin to fill a knowledge gap in menopausal care for women with HIV, in whom uptake of HT is very low.
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High human T cell leukaemia virus type 1c proviral loads are associated with diabetes and chronic kidney disease: results of a cross-sectional community survey in central Australia

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Abstract
Background
A link between chronic inflammation and several non-communicable diseases (NCD) has been established. Although chronic infection with the human T-cell leukaemia virus type 1 (HTLV-1) is the recognised cause of several inflammatory diseases and these are associated with a high number of HTLV-1 infected cells in peripheral blood (proviral load, PVL), possible interactions between PVL and NCDs have not been studied at a community level.
Methods
Adult Aboriginal residents of seven remote communities were invited to do a health survey between 25 August 2014 and 30 June 2018. Blood was drawn for HTLV-1 serology and PVL and relevant medical conditions were obtained from health records. Associations between HTLV-1 PVL and diabetes, chronic kidney disease (CKD), and coronary artery disease (CAD) were determined using logistic regression, adjusting for available confounders.
Results
Among 510 participants (56% of the estimated adult resident population, 922), 197 (38.6%) were HTLV-1 infected. A high HTLV-1 PVL was associated with a two-fold increase in the odds of diabetes and CKD (diabetes, adjusted odds ratio (aOR) 1.95 (95% confidence interval (CI), 1.06, 3.61, p = 0.033; CKD, aOR 2.00, 95% CI, 1.03, 3.8, p = 0.041). A non-significant association between high PVL and CAD (aOR, 7.08; 95% CI 1.00, 50.18; p = 0.05) was found for participants younger than 50 years at the time of angiography.
Conclusion
In a community-based study in central Australia people living with HTLV-1 who had high HTLV-1 PVL were more likely to have diabetes and CKD. These findings have potential clinical implications.
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Tenofovir Disoproxil Fumarate/Emtricitabine and Baricitinib for Patients at High Risk of Severe COVID-19: The PANCOVID Randomized Clinical Trial

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Abstract
Background
This study was designed to evaluate if patients with high risk for severe COVID-19 would benefit from treatment with TDF/FTC followed by baricitinib in case of hypoxemia and systemic inflammation.
Methods
PANCOVID is an open-label, double-randomized, phase 3 pragmatic clinical trial including adults with symptomatic COVID-19 with ≥ 2 comorbidities or older than 60 years conducted between 10 October 2020 and 23 September 2021. In the first randomization patients received TDF/FTC or not TDF/FTC. In the second randomization patients with room-air O2 saturation <95% and at least one increased inflammatory biomarker received baricitinib plus dexamethasone or dexamethasone alone. The primary endpoint was 28-day mortality. Main secondary endpoint was 28-day disease progression or critical care unit admission or mortality. The trial was stopped before reaching planned sample size due to the decrease in th e number of cases and a mortality rate substantially lower than expected EudraCT registration number: 2020-001156-18.
Results
Of the 355 included participants 97% were hospitalized at baseline. Overall, 28-day mortality was 3.1%. The 28-day mortality relative risk (RR) for participants treated with TDF/FTC was 1.76 (95% CI 0.52-5.91; p= 0.379); it was 0.42 (95% CI 0.11-1.59; p= 0.201) for those treated with baricitinib. The 28-day RR for the main secondary combined endpoint for participants treated with TDF/FTC was 0.95 (95% CI 0.66-1.40; p = 0.774); it was 0.90 (95%CI 0.61-1.33; p = 0.687) for those treated with baricitinib.
Conclusions
Our results do not suggest a beneficial effect of TDF/FTC; nevertheless, they are compatible with the beneficial effect of baricitinib already established by other clinical trials.
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