Κυριακή 16 Οκτωβρίου 2022

A Nationwide Evaluation of Bevacizumab-based Treatments in Paediatric Low-Grade Glioma in the UK: Safety. Efficacy, Visual Morbidity and Outcomes

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Abstract
Background
Bevacizumab is increasingly used in children with Paediatric Low-Grade Glioma (PLGG) despite limited evidence. A nationwide UK service evaluation was conducted to provide larger cohort 'real life' safety and efficacy data including functional visual outcomes.
Methods
Children receiving Bevacizumab-based treatments (BBT) for PLGG (2009-2020) from 11 centres were included. Standardised neuro-radiological (RANO-LGG) and visual (logMAR visual acuity) criteria were used to assess clinical-radiological correlation, survival outcomes and multivariate prognostic analysis.
Results
Eighty-eight children with PLGG received BBT either as 3 rd line with Irinotecan (85%) or alongside 1 st/2 nd line chemotherapies (15%). Toxicity was limited and minimal. Partial response (PR, 40%), stable disease (SD, 49%), and progressive disease (PD, 11%) were seen during BBT. However, 65% progressed at 8 months (median) from BBT cessation, leading to a radiology-based 3yr-progression-free survival (PFS) of 29%. Diencephalic syndrome (p= 0.03) was associated with adverse PFS. Pre-existing visual morbidity included unilateral (25%) or bilateral (11%) blindness. Improvement (29%) or stabilisation (49%) of visual acuity were achieved, more often in patients' best eyes. Vision deteriorated during BBT in 14 (22%), with 3-year visual-PFS of 53%; more often in patients' worst eyes. A superior visual outcome (p=0.023) was seen in Neurofibromatosis type 1-associated Optic Pathway Glioma (OPG). Concordance between visual and radiological responses was 36%; optimised to 48% using only best eye responses.
Conclusions
BBTs provide effective short-term PLGG control and delay further progression, with a better sustained visual (best >worst eye) than radiological response. Further research could optimise the role of BBTs towards a potentially sight-saving strategy in OPG.
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Πέμπτη 13 Οκτωβρίου 2022

Plasma Circulating Tumor HPV DNA and HPV-Related Oropharynx Cancer—A Caution—Reply

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In Reply Dr Johnson and colleagues raise a good point, as expressed in our article, that our findings should not be inferred to suggest that circulating tumor human papillomavirus (HPV) DNA (ctHPVDNA) is ready to be used for screening. Our observation that no ctHPVDNA was detected in healthy participants with detectable salivary HPV DNA or E6 serum antibody suggests a low false-positive rate (ie, suggests good specificity). However, as pointed out in the discussion of our research letter, and by Johnson et al, it is possible that the detecti on methods used in our study could be insensitive, and additional research is needed to verify the finding of high specificity in our study.
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Τετάρτη 12 Οκτωβρίου 2022

Maternal diet during breastfeeding in correlation to calcium and phosphorus concentrations in human milk

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Abstract

Background

The impact of maternal diet on minerals concentration in human milk (HM) remains unclear. The main aim of this study was to investigate the relationship between maternal dietary intake and calcium and phosphorus concentrations in HM. Furthermore, we aimed to evaluate the intake of both minerals by exclusively breastfed infants.

Methodology

HM samples were obtained from 30 mothers at 6-8 weeks postpartum. Each mother was asked to express pre- and post-feeding milk four times during 24-h period (6.00-12.00, 12.00-18.00, 18.00-24.00, 24.00-6.00). Maternal dietary assessment was based on food frequency questionnaire and 3-day dietary records. Analyzed minerals were determined by inductively coupled plasma mass spectrometer (NexION 300D ICP Mass Spectrometer, Perkin Elmer SCIEX, USA).

Results

The mean concentrations of calcium and phosphorus in HM samples were 278.7 ± 61.0 mg/L and 137.1 ± 21.9 mg/L, respectively, maintaining 2:1 ratio b y weight. The concentration of both minerals was correlated with each other (r=0.632, p=<0.001). The infants' mean calcium intake was 149.53 ± 36.41 mg/L and for phosphorus it was 74.62 ± 19.41 mg/L. The risk of insufficient intake of calcium was reported in 60% of infants (n=18). Spearman/Pearson correlation coefficients did not reveal any correlations between HM calcium concentration and maternal diet, contrary to HM phosphorus concentration, which was positively correlated with energy (r=0.369, p=0.045), total protein (r=0.464, p=0.01), calcium (r=385, p=0.036), phosphorus (r=501, p=0.005), niacin (p<0.001) and pyridoxine (r=382, 0.037) intake. However, in multivariable analysis we observed that maternal dietary intake of both minerals had positive influence on their concentration in HM.

Conclusion

Maternal calcium and phosphorus intake influenced concentration of both minerals in HM, however the relationship was rather weak. Additionally, we observed that c alcium intake by most of the exclusively breastfed infants was insufficient to meet the recommended daily intake.

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Optimizing SARS-CoV-2 Pooled Testing Strategies Through Differentiated Pooling for Distinct Groups

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Abstract
Pooled testing has been successfully used to expand SARS-CoV-2 testing, especially in settings requiring high volumes of screening of lower-risk individuals, but efficiency of pooling declines as prevalence rises.We propose a differentiated pooling strategy that independently optimizes pool sizes for distinct groups with different probabilities of infection to further improve the efficiency of pooled testing. We compare the efficiency (results obtained per test kit used) of the differentiated strategy to a traditional pooling strategy in which all samples are processed using uniform pool sizes under a range of scenarios.For most scenarios, differentiated pooling is more efficient than traditional pooling. In scenarios examined here, an improvement in efficiency of up to 3.94 results per test kit could be obtained through differentiated versus traditional pooling, with more likely scenarios resulting in 0.12 to 0.61 additional results per kit. Und er circumstances similar to those observed in a university setting, implementation of our strategy could result in an improvement in efficiency between 0.03 to 3.21 results per test kit.Our results can help identify settings, such as universities and workplaces, where differentiated pooling can conserve critical testing resources.
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Using indocyanine green angiography to achieve complete engraftment of pectoralis major myocutaneous flaps

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This report describes the usefulness of indocyanine green angiography (ICGA) to achieve complete engraftment of the PMMC flap. Five patients with oral cancer underwent reconstruction with a PMMC flap after cancer ablation. During the skin paddle design and flap elevation, the blood supply to the flap was assessed by ICGA. (Source: International Journal of Oral and Maxillofacial Surgery)
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Τρίτη 11 Οκτωβρίου 2022

Does ACE2 mediate the detrimental effect of exposures related to COVID‐19 risk: A Mendelian randomization investigation

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Abstract

Objectives

Adiposity, smoking and lower socioeconomic position (SEP) increase COVID-19 risk whilst the association of vitamin D, blood pressure, and glycemic traits in COVID-19 risk were less clear. Whether angiotensin-converting enzyme 2 (ACE2), the key receptor for SARS-CoV-2, mediates these associations has not been investigated. We conducted a Mendelian randomization study to assess the role of these exposures in COVID-19 and mediation by ACE2.

Methods

We extracted genetic variants strongly related to various exposures (vitamin D, blood pressure, glycemic traits, smoking, adiposity and educational attainment (SEP proxy)), and ACE2 cis-variants from genome wide association studies (GWAS, n ranged from 28,204 to 3,037,499) and applied them to GWAS summary statistics of ACE2 (n=28,204) and COVID-19 (severe, hospitalized, and susceptibility, n≤2,942,817). We used inverse variance weighted as the main analyses, with MR-Egger and weighted median as sensitivit y analyses. Mediation analyses were performed based on product of coefficient method.

Results

Higher adiposity, lifetime smoking index, and lower educational attainment were consistently associated with higher risk of COVID-19 phenotypes whilst there was no strong evidence for an association of other exposures in COVID-19 risk. ACE2 partially mediates the detrimental effects of body mass index (ranged from 4.3% to 8.2%), waist-to-hip ratio (ranged from 11.2% to 16.8%) and lower educational attainment (ranged from 4.0% to 7.5%) in COVID-19 phenotypes whilst ACE2 did not mediate the detrimental effect of smoking.

Conclusions

We provided genetic evidence that reducing ACE2 could partly lower COVID-19 risk amongst people who were overweight/obese or of lower SEP.

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High-Resolution Single Tooth MRI With an Inductively Coupled Intraoral Coil—Can MRI Compete With CBCT?

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imageObjectives The aims of this study were to quantify T1/T2-relaxation times of the dental pulp, develop a realistic tooth model, and compare image quality between cone-beam computed tomography (CBCT) and high-resolution magnetic resonance imaging (MRI) of single teeth using a wireless inductively coupled intraoral coil. Methods T1/T2-relaxometry was performed at 3 T in 10 healthy volunteers (283 teeth) to determine relaxation times of healthy dental pulp and develop a realistic tooth model using extracted human teeth. Eight MRI sequences (DESS, CISS, TrueFISP, FLASH, SPACE, TSE, MSVAT-SPACE, and UTE) were optimized for clinically applicable high-resolution imaging of the dental pulp. In model, image quality of all sequences was assessed quantitatively (contrast-to-noise ratio) and qualitatively (visibility of anatomical structures and extent of susceptibility artifacts using a 5-point scoring scale). Cone-beam computed tomography served as the reference modality for qualitative assessment. Statistical analysis was performed using 2-way analysis of variance, Fisher exact test, and Cohen κ. Results In vivo, relaxometry of dental pulps revealed T1/T2 relaxation times at 3 T of 738 ± 100/171 ± 36 milliseconds. For all sequences, an isotropic resolution of (0.21 mm)3 was achieved, with acquisition times ranging from 6:19 to 8:02 minutes. In model, the highest contrast-to-noise ratio values were observed for UTE, followed by TSE and CISS. The best image/artifact quality, however, was found for DESS (mean ± SD: 1.3 ± 0.3/2.2 ± 0.0), FLASH (1.5 ± 0.3/2.4 ± 0.1), and CISS (1.5 ± 0.4/2.5 ± 0.1), at a level comparable to CBCT (1.2 ± 0.3/2.1 ± 0.1). Conclusions Optimized MRI protocols using an intraoral coil at 3 T can achieve an image quality comparable to reference modality CBCT within clinically applicable acquisition times. Overall, DESS revealed the best results, followed by FLASH and CISS.
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