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Τετάρτη 25 Ιανουαρίου 2023

Enhanced recombination among omicron subvariants of SARS‐CoV‐2 contributes to viral immune escape

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Abstract

Genetic recombination is an important driver of SARS-CoV-2 evolution, which requires the co-infection of a single host cell with different SARS-CoV-2 strains. To understand the emergence and prevalence of recombinant SARS-CoV-2 lineages through time and space, we analyzed SARS-CoV-2 genome sequences collected from November 2019 to July 2022. We observed an extraordinary increase in the emergence of SARS-CoV-2 recombinant lineages during the Omicron wave, particularly in Northern America and Europe. This phenomenon was independent of the sequencing frequency or genetic diversity of circulating SARS-CoV-2 strains. The recombination breakpoints were more prevalent in the 3' UTR of the viral genome. Importantly, we noted the enrichment of certain amino acids in the spike protein of recombinant lineages, which have been reported to confer immune escape from neutralizing antibodies and increase ACE2 receptor binding in some cases. We also observed I42V amino acid change genetically fi xated in the NSP14 of the Omicron lineage, which needs further characterization for its potential role in enhanced recombination. Overall, we report the important and timely observation of accelerated recombination in the currently circulating SARS-CoV-2 Omicron variants and explore their potential contribution to viral fitness, particularly immune escape.

This article is protected by copyright. All rights reserved.

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Use of gemcitabine, oxaliplatin, and anti‐CD20 therapy in children and adolescents with non‐Hodgkin lymphoma unfit for intensive therapy

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Abstract

Multiagent immunochemotherapy affords excellent outcomes in pediatric non-Hodgkin lymphoma (NHL); however, scarce data exist for patients unfit for intensive treatment. Rituximab, gemcitabine, and oxaliplatin (R-GemOx) is well tolerated and efficacious in elderly adults with NHL; however, its use has not been described in pediatrics. In this retrospective, single-center study, six children with mature B-cell NHL and significant comorbidities received anti-CD20 therapy with GemOx (rituximab or obinutuzumab or ofatumumab with gemcitabine and oxaliplatin [R/O-GemOx]). R/O-GemOx was well tolerated and resulted in complete response in two of three patients with newly diagnosed NHL and one of three patients with primary refractory NHL. R/O-GemOx is a viable treatment option for children with NHL who cannot tolerate intensive therapy.

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Serial In‐Office Steroid Injections for Airway Stenosis: Long‐Term Benefit and Cost Analysis

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Serial In-Office Steroid Injections for Airway Stenosis: Long-Term Benefit and Cost Analysis

Serial in office steroid injection help avoid operative intervention regardless of stenosis etiology. Follow up of at least 2 years suggest that serial in office steroid injection can avoid operative intervention long term. There is potential cost savings associated with serial steroid injection over traditional endoscopic dilation.


Objectives

To evaluate the long-term benefit of serial in-office steroid injections (SISI) in the treatment of subglottic and proximal tracheal stenosis (SG/PTS). Evaluate cost of SISI compared to endoscopic dilation (ED).

Study Design

Retrospective study and cost analysis.

Methods

All patients with SGS/PTS with at least two consecutive in-office steroid injections between 2013 and 2021 were evaluated. Patients with less than 2 years of follow-up data after the initial SISI series were excluded. Demographics, etiology of stenosis, total injections performed, time between steroid series, surgery-free interval (SFI) and adverse events were collected. For patients with known surgical history before SISI, pre-SISI SFI was compared. Institutional billing records and the national CMS average reimbursement were evaluated. Total charges for three treatment strategies (ED alone, ED with post-operative SISI and primary intervention with SISI) were also compared.

Results

Forty-nine patients were included; 29 (59%) idiopathic, 11 (22%) traumatic and 9 (18%) rheumatologic. Mean (SD) follow-up time after the first SISI was 3.41 years (1.5), range (2.08–7.25 years). 79% (39/49) did not require additional surgery during the entire follow-up period. The SFI improved from a mean 13.5 months (SD 12.6; range 2–42 months) pre-SISI to a mean (SD) of 42 months (SD 20.2; range 10–87 months) (p < 0.0001) after SISI. Annual average charges for ED alone in our cohort was $15,383.28, compared to $7,070.04 for SISI.

Conclusions

SISI are an effective treatment for patients with SG/PTS. In-office steroid injections could offer cost savings for the patient.

Level of Evidence

4 Laryngoscope, 2023

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Radiological evolution of progestogen‐induced meningioma: A monocentric retrospective study

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Abstract

Context

Cyproterone acetate (CPA) is known to induce meningioma, and recently, nomegestrol acetate (NMA) and chlormadinone acetate (CMA) were also involved. Progestagen-induced meningioma management starts with progestogen discontinuation and is either interventional (surgery and/or radiotherapy) or conservative (clinical and MRI radiological follow-up). We performed a retrospective volumetric radiological outcome study of progestogen-induced meningiomas diagnosed in our hospital.

Method

We analysed progestogen-related meningiomas diagnosed until 30 June 2021, with at least one diagnostic and one follow-up MRI results. Meningioma volumes were centrally retrospectively measured using a T1-weighted 3D millimeter sequence with gadolinium injection on a post-processing console.

Results

We analysed 98 meningiomas of 38 females and one transgender (male-to-female), of which 25 (64.1%) had taken CPA, 7 (17.9%) NMA, 3 (7.7%) CMA, and 4 (10.2%) several progestogens. Eleven patients (24 meningiomas) underwent interventional management, 7 patients had meningiomas followed by conservative or interventional management, and 21 patients (51 meningiomas) had only conservative management. Of these 21 patients, 17 had discontinued their progestogen less than 6 months before, of which 14 (82.3%) had decreased or stable meningioma(s) during a 24-month median follow-up [3 to 75] period.

Overall

four of the 39 patients experienced meningioma progression (three during conservative treatment and one after surgery), including two patients who had continued NMA or CMA treatment several years after diagnosis.

Conclusion

Our study confirms a generally favorable outcome of progestogen-related meningioma after conservative treatment, especially for CPA. It also underlines the need for progestogen discontinuation at meningioma diagnosis.

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Τρίτη 24 Ιανουαρίου 2023

Merkelzellkarzinom

alexandrossfakianakis shared this article with you from Inoreader

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Laryngorhinootologie
DOI: 10.1055/a-1949-3751

Das Merkelzellkarzinom ist ein aggressiver neuroendokriner Tumor, welcher durch schnelles Wachstum und frühzeitige Metastasierung charakterisiert ist. Das mediane Erkrankungsalter liegt zwischen 75–80 Jahren. Mit Zunahme des durchschnittlichen Bevölkerungsalters tritt der einstmals seltene Tumor immer häufiger auf. Neben den klassischen Therapiesäulen Chirurgie, Strahlentherapie und Chemotherapie spielt die Immunonkologie au ch beim Merkelzellkarzinom eine zunehmend wichtige Rolle.
[...]

Georg Thieme Verlag KG Rüdigerstraße 14, 70469 Stuttgart, Germany

Article in Thieme eJournals:
Table of contents  |  Abstract  |  Full text

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Δευτέρα 23 Ιανουαρίου 2023

Role of craniofacial phenotypes in the response to oral appliance therapy for obstructive sleep apnea

alexandrossfakianakis shared this article with you from Inoreader

Abstract

Background

Mandibular advancement device (MAD) is a good alternative for patients with obstructive sleep apnea (OSA). However, the treatment response varies among individuals.

Objective

This study aimed to explore the role of craniofacial features in the response to MADs to improve prognostication and patient selection.

Methods

The retrospective trial contained 42 males aged 41.5±9.0 years, and with an apnea-hypopnea index (AHI) of 21.5±13.8 events/h. According to the mandibular plane angle, participants were divided into three groups: low angle (n=13), average angle (n=14), and high angle (n=15). Under monitor of home sleep testing, adjustable MADs were used to titrate the mandible forward from 0 mm with an increment of 0.5 mm every day. The polysomnography outcomes, mandibular protrusion amounts, changes in upper airway MRI measurements, and nasal resistance were compared among three groups.

Results

The normalization rate (AHI < 5 /h) was 92.3%, 57.1%, and 46.7% respectively in the low, average, and high angle groups (p=0.027). The effective protrusion where AHI was reduced by half was 20 (11.3~37.5) %, 31.3 (23.6~50) %, and 50 (36.9~64.9) % of the maximal mandibular protrusion, in the low, average, and high angle groups (p=0.004). Multivariate logistic regression revealed that increased gonion angle (OR=0.878) and baseline AHI(OR=0.868) can reduce the probability of normalization.

Conclusion

The high mandibular plane angle might be an unfavorable factor to MAD treatment and more protrusion was needed to achieve a 50% reduction in AHI. Vertical craniofacial pattern (gonion angle) and baseline AHI constituted the model for predicting the effect of MADs.

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GBMdeconvoluteR accurately infers proportions of neoplastic and immune cell populations from bulk glioblastoma transcriptomics data

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Abstract
Background
Characterising and quantifying cell types within glioblastoma (GBM) tumours at scale will facilitate a better understanding of the association between the cellular landscape and tumour phenotypes or clinical correlates. We aimed to develop a tool that deconvolutes immune and neoplastic cells within the GBM tumour microenvironment from bulk RNA sequencing data.
Methods
We developed an IDH wild-type (IDHwt) GBM-specific single immune cell reference consisting of B cells, T cells, NK cells, microglia, tumour associated macrophages, monocytes, mast and DC cells. We used this alongside an existing neoplastic single cell-type reference for astrocyte-like, oligodendrocyte- and neuronal-progenitor like and mesenchymal GBM cancer cells to create both marker and gene signature matrix-based deconvolution tools. We applied single-cell resolution imaging mass cytometry (IMC) to ten IDHwt GBM samples, five paired primary and recur rent tumours, to determine which deconvolution approach performed best.
Results
Marker based deconvolution using GBM tissue specific markers was most accurate for both immune cells and cancer cells, so we packaged this approach as GBMdeconvoluteR. We applied GBMdeconvoluteR to bulk GBM RNAseq data from The Cancer Genome Atlas and recapitulated recent findings from multi-omics single cell studies with regards associations between mesenchymal GBM cancer cells and both lymphoid and myeloid cells. Furthermore, we expanded upon this to show that these associations are stronger in patients with worse prognosis.
Conclusions
GBMdeconvoluteR accurately quantifies immune and neoplastic cell proportions in IDHwt GBM bulk RNA sequencing data and is accessible here: https : // gbmdeconvoluter.leeds.ac.uk
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