Τρίτη 31 Ιανουαρίου 2023

Detect and suppress future zoonotic‐derived outbreaks: A lesson from last two decades

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Abstract

COVID-19 pandemic has revealed how vulnerable and inexperienced we are when dealing with an unprecedented global infectious threat. Looking back on the last few decades, there has been a surge in zoonotic-derived viruses globally. Notably, these outbreaks emerged as harmless zoonotic diseases within a favorable environment, then spilled over to humans and widely spread to become outbreaks. Most of these are respiratory viruses (particularly Orthomyxoviridae Orthomyxoviridae or Coronaviridae Coronaviridae family), with high transmissibility and can be easily spread. Low- and middle-income countries, particularly those with tropical climates, provide ideal environments for the growth and evolution of these zoonotic viruses. Nevertheless, a lot of our advanced centers for infectious diseases are located in high-income countries (HIC) and focus on human pathogens only (e.g., influenza, RSV, adenovirus). We should critically think about reallocating health resources in th e near-term. It is an urge for a few surveillance centers aim to detect surges in cases of respiratory pathogens or any spikes in cases, and suppress the transmission chain from an early stage. In this article, we digest lessons learned from the previous spillover pandemics and suggest actionable tactics to deal with future pandemics properly.

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Genetic characteristics and treatment outcome in infants with KMT2A germline B‐cell precursor acute lymphoblastic leukemia: Results of MLL‐Baby protocol

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Abstract

The aim of this study was to present the diagnostic and outcome characteristics of infants with germline status of KMT2A gene (KMT2A-g) B-cell precursor acute lymphoblastic leukemia (BCP-ALL) treated consistently according to the MLL-Baby protocol, a moderate-intensity protocol. Of the 139 patients enrolled in the MLL-Baby study, 100 (71.9%) carried different types of rearranged KMT2A (KMT2A-r), while the remaining 39 infants (28.1%) had KMT2A-g. KMT2A-g patients were generally older (77% older than 6 months), less likely to have a very high white blood cell count (greater than 100 × 109/L), less likely to be central nervous system (CNS)-positive, and more likely to be CD10-positive. The 6-year event-free survival and overall survival rates for all 39 patients were 0.74 (standard error [SE] 0.07) and 0.80 (SE 0.07), respectively. Relapse was the most common adverse event (n = 5), with a cumulativ e incidence of relapse (CIR) of 0.13 (SE 0.06), while the incidence of a second malignancy (n = 1) and death in remission (n = 3) was 0.03 (SE 0.04) and 0.08 (SE 0.04), respectively. None of the initial parameters, including genetics and the presence of recently described fusions of NUTM1 and PAX5 genes, was able to distinguish patients with different outcomes. Only rapidity of response, measured as minimal residual disease (MRD) by flow cytometry, showed a statistically significant impact. Moderate-intensity therapy, as used in the MLL-Baby protocol in infants with KMT2A-g BCP-ALL, yields results comparable to other infant studies. Patients with a slow multicolor flow cytometry (MFC)-MRD response should be subjected to advanced therapies, such as targeted or immunotherapies.
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The incidence and characterization of weight gain associated with MEK inhibitors in pediatric patients

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Abstract

Background

Mitogen-activated protein kinase enzyme (MEK) inhibitors are used in the treatment of pediatric patients with neurofibromatosis, low grade glioma, and astrocytoma, and may demonstrate a unique side effect profile in this population. Inhibition of MEK has been shown to decrease interleukin (IL)-6 production, a proinflammatory cytokine. The inhibition of IL-6 and other proinflammatory cytokines is thought to decrease muscle wasting and may contribute to weight gain.

However, there is limited information on the association of MEK inhibition and weight gain in children and adolescents. This study aimed to characterize and define the incidence of significant weight gain associated with MEK inhibitors in pediatric patients.

Methods

This was a retrospective chart review conducted at a tertiary pediatric hospital. Children 1–18.99 years old were included if they started a MEK inhibitor from July 1, 2013–October 31, 2021, and continued therapy for at least 6 months. Significant weight gain was defined as ≥5% increase in patient's weight-for-age percentile.

Results

Sixty-seven patients were included in the analysis. Sixty-two received trametinib and 5 received selumetinib. An increase in weight-for-age percentile ≥5% was seen in 60% of patients receiving selumetinib and 56% on trametinib. The Dunnett's multiple comparisons test revealed a difference in weight-for-age percentile from baseline to end of data collection (p = .0173). Patients who were obese at baseline were more likely to lose weight during treatment, while underweight patients increased in weight-for-age percentiles.

Conclusions

Weight gain may be a notable side effect associated with the use of MEK inhibitors in pediatric patients.
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Automated Creak Differentiates Adductor Laryngeal Dystonia and Muscle Tension Dysphonia

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Objective

The purpose of this study was to determine whether automated estimates of vocal creak would differentiate speakers with adductor laryngeal dystonia (AdLD) from speakers with muscle tension dysphonia (MTD) and speakers without voice disorders.

Methods

Sixteen speakers with AdLD, sixteen speakers with MTD, and sixteen speakers without voice disorders were recorded in a quiet environment reading aloud a standard paragraph. An open-source creak detector was used to calculate the percentage of creak (% creak) in each of the speaker's six recorded sentences.

Results

A Kruskal-Wallis one-way analysis of variance revealed a statistically significant effect of group on the % creak with a large effect size. Pairwise Wilcoxon tests revealed a statistically significant difference in % creak between speakers with AdLD and controls as well as between speakers with AdLD and MTD. Receiver operating characteristic curve analyses indicated that % creak differentiated AdLD from both controls and speakers with MTD with high sensitivity and specificity (area under the curve statistics of 0.94 and 0.86, respectively).

Conclusion

Percentage of creak as calculated by an automated creak detector may be useful as a quantitative indicator of AdLD, demonstrating the potential for use as a screening tool or to aid in a differential diagnosis.

Level of Evidence

3 Laryngoscope, 2023
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Use of incorrect and correct methods to account for age in studies on epigenetic accelerated aging: implications and recommendations for best practices

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Abstract
Motivated by our conduct of a literature review on social exposures and accelerated aging as measured by a growing number of epigenetic "clocks" (which estimate age via DNA methylation patterns (DNAm)), we report on three different approaches – 1 incorrect and 2 correct – in the epidemiologic literature on treatment of age in these and other studies using other common exposures (i.e., body mass index and alcohol consumption). Among the 50 empirical articles reviewed, the majority (n = 29; 58%) used the incorrect method of analyzing accelerated aging detrended for age as the outcome and did not control for age as a covariate. By contrast, only 42% used the correct methods, which are either to analyze accelerated aging detrended for age as the outcome and control for age as a covariate (n = 16; 32%), or to analyze raw DNAm age as the outcome and control for age as a covariate (n = 5; 10%). In accord with prior demonstrations of bias introdu ced by the incorrect approach, we provide simulation analyses and additional empirical analyses to illustrate how the incorrect method can lead to bias to the null, and we discuss implications for extant research and recommendations for best practices.
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Δευτέρα 30 Ιανουαρίου 2023

Risk prediction in early childhood SHH medulloblastoma treated with radiation-avoiding chemotherapy: Evidence for more than two subgroups

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Abstract
Background
The prognostic impact of clinical risk factors and DNA methylation patterns in sonic hedgehog (SHH)-activated early childhood desmoplastic/nodular medulloblastoma (DMB) or medulloblastoma with extensive nodularity (MBEN) were evaluated to better identify patients at risk for relapse.
Methods
Hundred-forty-four patients with DMB (n=99) or MBEN (n=45) aged <5 years and treated with radiation-sparing approaches, including intraventricular methotrexate in 132 patients, were evaluated.
Results
Patients with DMB had less favorable 5-year progression-free survival than MBEN (5y-PFS, 71% [DMB] vs 93% [MBEN]). Patients' age >3 years was associated with more unfavorable 5y-PFS (47% [>3 years] vs 85% [<1 year] vs 84% [1-3 years]). DNA methylation profiles available (n=78) were reclassified according to the 2021 WHO classification into SHH-1 (n=39), SHH-2 (n=38), and SHH-3 (n=1). Hierarchical clustering de lineated two subgroups among SHH-2: SHH-2a (n=19) and SHH-2b (n=19). Patients with SHH-2b medulloblastoma were older, predominantly displayed DMB histology, and were more often located in the cerebellar hemispheres. Chromosome 9q losses were more frequent in SHH-2b, while few chromosomal alterations were observed in SHH-2a. SHH-2b medulloblastoma carried a significantly increased relapse risk (5y-PFS: 58% [SHH-2b] vs 83% [SHH-1] vs 95% [SHH-2a]). Subclassification of SHH-2 with key clinical and cytogenetic characteristics was confirmed using two independent cohorts (total n=188). Gene mutation analysis revealed a correlation of SHH-2a with SMO mutations.
Conclusion
These data suggest further heterogeneity within early childhood SHH-DMB/MBEN: SHH-2 splits into a very low-risk group SHH-2a enriched for MBEN histology and SMO mutations, and SHH-2b comprising older DMB patients with higher risk of r elapse.
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Photo‐/ mechanical and physical implant surface decontamination approaches in conjunction with surgical peri‐implantitis treatment: A systematic review

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Abstract

Aim

To evaluate the efficacy of adjunctive/alternative photo-/mechanical and physical implant-surface decontamination approaches compared to a standard instrumentation in conjunction with surgical peri-implantitis treatment.

Materials and Methods

Randomized controlled clinical trials (RCTs) and controlled clinical trials (CCTs) investigating the efficacy of adjunctive or alternative photo-/mechanical/physical measures for implant surface decontamination in conjunction with surgical peri-implantitis treatment without (PICOS 1) or with (PICOS 2) additional decontamination methods performed in test and control groups with changing inflammation parameters. Changes in bleeding scores (i.e., bleeding index (BI), or bleeding on probing (BOP)), suppuration (SUP) and PD values were considered as primary outcomes.

Results

Six articles describing five original RCTs were eligible for analysis. Based on two RCTs, the adjunctive/alternative use of an air polishing with glycine or erythritol powders did not improve BOP reduction compared to a standard instrumentation (PICOS 1). Based on one RCT, alternative use of titanium brushes resulted in significantly higher BOP reduction compared to either air polishing or a standard instrumentation (PICOS 1). During reconstructive therapy and as an adjunct to implantoplasty, use of a titanium brush did not have a benefit on the BOP and mean PD reductions compared to the control group (i.e., implantoplasty + mechanical and chemical implant surface decontamination; 1 RCT; PICOS 2). An Er:YAG laser resulted in significantly higher PD reduction after 6 months (1 RCT), whereas no difference between the test and respective controls could be detected after 1 and 2 years (1 RCT). Additionally, the use of the Er:YAG laser was not associated with improved BOP reductions over respective controls (2 RCTs; PICOS 2).

Conclusions

Due to the limited available data, clinical efficacy of photo-/mechanical and physical implant surface decontamination in conjunction with surgical peri-implantitis therapy is inconclusive. However, titanium brushes may be beneficial in reducing signs of inflammation.
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Accuracy of implant placement using CAD‐CAM tooth‐supported surgical guides for an auricular prosthesis in vitro

alexandrossfakianakis shared this article with you from Inoreader

Abstract

Purpose

To evaluate the accuracy of tooth-supported surgical guides used to place implants in auricular prostheses. The accuracy (trueness and precision) of the implant positions was evaluated, and the difference between the surgical guide with and without retention of the external auditory canal was compared.

Materials and methods

This study simulated implant placement in vitro for the treatment of right auricle malformation. Surgical guides and other casts were fabricated using additive manufacturing technology. The casts were divided into two groups according to the surgical guide, with 10 bone blocks in each group (with or without the external auditory canal plug (Guide 1 and Guide 2)). Three implant positions (Implants 1, 2, and 3) were prepared for each bone block using surgical guides. Implant positions were registered using light-body silicone impressions combined with optical surface scans to measure the coronal, apical, depth, and angular deviations. Four deviations of trueness and precision were reported as the mean ± standard deviation which was analyzed by Student's t-test.

Results

Each group of 10 bone blocks with 30 implant positions were successfully prepared and digitally reproduced as implants. The accuracy of implant position with surgical guides were acceptable when compared with the preoperatively planned implant positions. Compared with the Guide 2 group, there was a significant difference in the apical, depth, and angular deviations of Guide 1 group in terms of precision (p<0.001). There was a significant difference in the depth deviation of Implant 1 (p = 0.028) and apical deviation of Implant 2 (p<0.001) compared two groups in terms of trueness. In terms of precision, there was a significant difference in the coronal (p = 0.002), apical (p<0.001), and depth (p<0.001) deviation of Implant 1; apical (p = 0.036) and angular (p<0.001) deviation of Implant 2 also existed significant difference; the coronal deviation of Implant 3 (p = 0.018) also existed significant difference. Moreover, the group with the external auditory canal plug showed lower deviation in precision and a smaller volume in the 95% confidence ellipsoid.

Conclusion

Both types of tooth-supported surgical guides can provide acceptable accuracy. A surgical guide with an external auditory canal plug was considered to be more precise.

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A Novel Sampling Device for the Quantification of Primary Aromatic Amines on Surfaces

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Abstract
Primary aromatic amines (PAAs) are a class of hazardous substances where many compounds are classified as carcinogen, mutagen, and reproduction toxin (CMR). PAAs can be taken up by dermal exposure. In the polyurethane industry, a valid and trustworthy method for the quantification of PAAs in the presence of isocyanates that could interfere is of great interest, especially on workplaces where a regular contact to PAAs cannot be excluded. The aim of this work is the development, validation, and verification of a novel sampling device to quantify selectively the PAA load on work surfaces. We describe the synthesis of Cell-ßALA-PEMSA analytical papers and their characterization by infrared spectroscopy and thermogravimetric analysis. The recovery of TDA and MDA spiked on these filters is satisfactory. An excellent selectivity of Cell-ßALA-PEMSA papers towards PAAs in the presence of isocyanates of almost 100% was found by wipe tests of amine/isocya nate contaminated surfaces. First positive field tests were achieved at certain areas in a Polyurethane Technical Application Department where surface contamination with PAAs was expected, and the Cell-ßALA-PEMSA analytical papers were superior to an established method of surface sampling. However, recovery of these amines from surfaces shows a large variability, and more work is required to address influencing surface properties.
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Severe Fatigue and Persistent Symptoms at Three Months Following SARS-CoV-2 Infections During the Pre-Delta, Delta, and Omicron Time Periods: A Multicenter Prospective Cohort Study

alexandrossfakianakis shared this article with you from Inoreader
ABSTRACT
Background
Most research on SARS-CoV-2 variants focuses on initial symptomatology with limited data on longer-term sequelae. We sought to characterize the prevalence and differences in prolonged symptoms at three months post SARS-CoV-2-infection across the three major variant time-periods (pre-Delta, Delta, and Omicron).
Methods
This multicenter prospective cohort study of adults with acute illness tested for SARS-CoV-2 compared fatigue severity, fatigue symptoms, individual and organ system-based symptoms, and presence of ≥3 total symptoms across variants among COVID-positive and COVID-negative participants 3 months after their initial SARS-CoV-2 diagnosis. Variant periods were defined by dates with ≥50% dominant strain. We performed a sensitivity analysis using ≥90% dominance threshold and multivariable logistic regression modeling to estimate the independent effects of each variant adjusting for socio-demographic chara cteristics, baseline health, and vaccine status.
Results
The study included 3,223 participants (2,402 COVID-positive and 821 COVID-negative). Among the COVID-positive cohort, 463 (19.3%) were pre-Delta, 1,198 (49.9%) during Delta, and 741 (30.8%) during Omicron. Prolonged severe fatigue was highest in the pre-Delta COVID-positive cohort compared with Delta and Omicron cohorts (16.7% vs 11.5% vs 12.3%, respectively; p = 0.017), as was presence of ≥3 prolonged symptoms (28.4% vs 21.7% vs 16.0%; p < 0.001). No difference was seen in the COVID-negative cohort between variant time-periods. In multivariable models, there was no difference in severe fatigue between variants. There was decreased odds of having ≥3 symptoms in Omicron compared with other variants; this was not significant after adjusting for vaccination status.
Conclusions
Prolonged symptoms following SARS-CoV-2 infection were more common among participants infected during the pre-Delta period compared with Delta and Omicron periods; however, these differences were no longer significant after adjusting for vaccination status. This suggests a potential beneficial effect of vaccination on the risk of developing long-term symptoms.
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