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

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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

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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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