Isolation of Mesenchymal Stem Cells (MSCs) from Wharton’s Jelly (WJ) Tissue of Human Umbilical Cord (hUC); a Protocol

Mesenchymal stem cells (MSCs) with their spindle like shapes are a lineage of stem cells with the capacity to self-renew and differentiate into osteoblasts, adipocytes, and chondrocytes and with CD105, CD73, and CD90 expression and the lack of CD34, CD14, CD45, and HLA - DR expression. The immunomodulatory, angiogenic, antiapoptotic, antimicrobial, and antioxidative characteristics of these cells made them more attractive in the field of cell - therapy for several autoimmune and inflammatory diseases, including diabetes, neurological disorders, sepsis, cardiac ischemia, and GvHD. For this reason, various protocols have been proposed to isolate mesenchymal stem cells from different tissue sources, such as adipose tissue (AT), umbilical cord (UC), Wharton’s jelly (WJ), bone marrow (BM), dental pulp, and even menstrual fluid. Considering the ease of access to the umbilical cord tissue and the fact that this tissue is rich in MSCs with embryonic origin and higher proliferation rate and lower senescence of the cells, the umbilical cord became a suitable source for explant MSC culture. In this study, we decided to introduce an explant culture protocol of MSCs that is less expensive and cost - effective achieving a high yield of MSCs

Clinically Valuable Quality Control for PET/MRI Systems:Consensus Recommendation From the HYBRID Consortium

International audienceQuality control (QC) of medical imaging devices is essential to ensure their proper function and to gain accurate and quantitative results. Therefore, several international bodies have published QC guidelines and recommendations for a wide range of imaging modalities to ensure adequate performance of the systems. Hybrid imaging systems such as positron emission tomography/computed tomography (PET/CT) or PET/magnetic resonance imaging (PET/MRI), in particular, present additional challenges caused by differences between the combined modalities. However, despite the increasing use of this hybrid imaging modality in recent years, there are no dedicated QC recommendations for PET/MRI. Therefore, this work aims at collecting information on QC procedures across a European PET/MRI network, presenting quality assurance procedures implemented by PET/MRI vendors and achieving a consensus on PET/MRI QC procedures across imaging centers. Users of PET/MRI systems at partner sites involved in the HYBRID consortium were surveyed about local frequencies of QC procedures for PET/MRI. Although all sites indicated that they perform vendor-specific daily QC procedures, significant variations across the centers were observed for other QC tests and testing frequencies. Likewise, variations in available recommendations and guidelines and the QC procedures implemented by vendors were found. Based on the available information and our clinical expertise within this consortium, we were able to propose a minimum set of PET/MRI QC recommendations including the daily QC, cross-calibration tests, and an image quality (IQ) assessment for PET and coil checks and MR image quality tests for MRI. Together with regular checks of the PET-MRI alignment, proper PET/MRI performance can be ensured

The clinical and genetic spectrum of autosomal-recessive TOR1A-related disorders.

In the field of rare diseases, progress in molecular diagnostics led to the recognition that variants linked to autosomal-dominant neurodegenerative diseases of later onset can, in the context of biallelic inheritance, cause devastating neurodevelopmental disorders and infantile or childhood-onset neurodegeneration. TOR1A-associated arthrogryposis multiplex congenita 5 (AMC5) is a rare neurodevelopmental disorder arising from biallelic variants in TOR1A, a gene that in the heterozygous state is associated to torsion dystonia-1 (DYT1 or DYT-TOR1A), an early-onset dystonia with reduced penetrance. While 15 individuals with TOR1A-AMC5 have been reported (less than 10 in detail), a systematic investigation of the full disease-associated spectrum has not been conducted. Here, we assess the clinical, radiological and molecular characteristics of 57 individuals from 40 families with biallelic variants in TOR1A. Median age at last follow-up was 3 years (0-24 years). Most individuals presented with severe congenital flexion contractures (95%) and variable developmental delay (79%). Motor symptoms were reported in 79% and included lower limb spasticity and pyramidal signs, as well as gait disturbances. Facial dysmorphism was an integral part of the phenotype, with key features being a broad/full nasal tip, narrowing of the forehead and full cheeks. Analysis of disease-associated manifestations delineated a phenotypic spectrum ranging from normal cognition and mild gait disturbance to congenital arthrogryposis, global developmental delay, intellectual disability, absent speech and inability to walk. In a subset, the presentation was consistent with fetal akinesia deformation sequence with severe intrauterine abnormalities. Survival was 71% with higher mortality in males. Death occurred at a median age of 1.2 months (1 week - 9 years) due to respiratory failure, cardiac arrest, or sepsis. Analysis of brain MRI studies identified non-specific neuroimaging features, including a hypoplastic corpus callosum (72%), foci of signal abnormality in the subcortical and periventricular white matter (55%), diffuse white matter volume loss (45%), mega cisterna magna (36%) and arachnoid cysts (27%). The molecular spectrum included 22 distinct variants, defining a mutational hotspot in the C-terminal domain of the Torsin-1A protein. Genotype-phenotype analysis revealed an association of missense variants in the 3-helix bundle domain to an attenuated phenotype, while missense variants near the Walker A/B motif as well as biallelic truncating variants were linked to early death. In summary, this systematic cross-sectional analysis of a large cohort of individuals with biallelic TOR1A variants across a wide age-range delineates the clinical and genetic spectrum of TOR1A-related autosomal-recessive disease and highlights potential predictors for disease severity and survival

Improved Positron Emission Tomography Quantification: Evaluation of a Maximum-Likelihood Scatter Scaling Algorithm

Incorrect scatter scaling of positron emission tomography (PET) images can lead to halo artifacts, quantitative bias, or reconstruction failure. Tail-fitted scatter scaling (TFSS) possesses performance limitations in multiple cases. This study aims to investigate a novel method for scatter scaling: maximum-likelihood scatter scaling (MLSS) in scenarios where TFSS tends to induce artifacts or are observed to cause reconstruction abortion. [68Ga]Ga-RGD PET scans of nine patients were included in cohort 1 in the scope of investigating the reduction of halo artifacts relative to the scatter estimation method. PET scans of 30 patients administrated with [68Ga]Ga-uPAR were included in cohort 2, used for an evaluation of the robustness of MLSS in cases where TFSS-integrated reconstructions are observed to fail. A visual inspection of MLSS-corrected images scored higher than TFSS-corrected reconstructions of cohort 1. The quantitative investigation near the bladder showed a relative difference in tracer uptake of up to 94.7%. A reconstruction of scans included in cohort 2 resulted in failure in 23 cases when TFSS was used. The lesion uptake values of cohort 2 showed no significant difference. MLSS is suggested as an alternative scatter-scaling method relative to TFSS with the aim of reducing halo artifacts and a robust reconstruction process

Clinically Valuable Quality Control for PET/MRI Systems: Consensus Recommendation From the HYBRID Consortium

status: publishe

SARS-CoV-2 vaccination modelling for safe surgery to save lives: data from an international prospective cohort study

Background: Preoperative SARS-CoV-2 vaccination could support safer elective surgery. Vaccine numbers are limited so this study aimed to inform their prioritization by modelling. Methods: The primary outcome was the number needed to vaccinate (NNV) to prevent one COVID-19-related death in 1 year. NNVs were based on postoperative SARS-CoV-2 rates and mortality in an international cohort study (surgical patients), and community SARS-CoV-2 incidence and case fatality data (general population). NNV estimates were stratified by age (18-49, 50-69, 70 or more years) and type of surgery. Best- and worst-case scenarios were used to describe uncertainty. Results: NNVs were more favourable in surgical patients than the general population. The most favourable NNVs were in patients aged 70 years or more needing cancer surgery (351; best case 196, worst case 816) or non-cancer surgery (733; best case 407, worst case 1664). Both exceeded the NNV in the general population (1840; best case 1196, worst case 3066). NNVs for surgical patients remained favourable at a range of SARS-CoV-2 incidence rates in sensitivity analysis modelling. Globally, prioritizing preoperative vaccination of patients needing elective surgery ahead of the general population could prevent an additional 58 687 (best case 115 007, worst case 20 177) COVID-19-related deaths in 1 year. Conclusion: As global roll out of SARS-CoV-2 vaccination proceeds, patients needing elective surgery should be prioritized ahead of the general population