The VES-Matic 5 is an automated analyzer that assesses erythrocyte sedimentation rate based on a modified Westergren sedimentation technique. Instrument performance was established by addressing the ...recommendations of the International Council for Standardization in Haematology.
Comparison against the reference Westergren method was performed for all samples, and further for the low, middle, and upper third of the analytical range. Intra-run precision, inter-run precision, and interference studies were further assessed. This study included the evaluation of reference ranges.
The comparison of methods by Passing-Bablok analysis has shown a good agreement without systematic or proportional differences. The regression equation was
=-0.646 + 0.979x. The mean bias of -0.542 was obtained by Bland-Altman analysis and the upper limit of 8.03 with the lower limit of -9.11 can be considered clinically acceptable. Intra-run and inter-run precision were good for each parameter and interference studies did not show any significant bias with exception of anemia samples, which showed a proportional difference when comparing high erythrocyte sedimentation rate values. Using the local adult reference population, we verified the reference ranges in comparison to those available in the literature, and according to the Clinical Laboratory Standards Institute (CLSI) EP28-A3C document. We determined the upper limit partitioned by gender and the following age groups: from 18 to 50, from 50 to 70, and over 70.
The VES-Matic 5 analyzer presented good comparability with the reference method. As there are commercial quality control and suitable external quality assessment (EQA) material and programs, the VES-Matic 5 can be employed appropriately for routine purposes.
•Saliva is an eligible matrix for SARS-CoV-2 molecular detection and IgA measurement.•Saliva collection offers several advantages: safe, non-invasive and self-collection.•Positive molecular testing ...results were associated with disease duration.•The presence of salivary IgA was associated with pneumonia and CRP values.
This study aims to verify whether standardized saliva collection is suitable for SARS-CoV-2 molecular detection and IgA measurement.
43 COVID-19 inpatients and 326 screening subjects underwent naso-pharyngeal (NP)-swab and saliva collection (Salivette). Inpatients also underwent repeated blood collections to evaluate inflammation and organs involvement. In all patients and subjects, SARS-CoV-2 (gene E) rRT-PCR was undertaken in saliva and NP-swabs. Salivary IgA and serum IgA, IgG, IgM were measured on inpatients’ samples.
NP-swabs and saliva were both SARS-CoV-2 positive in 7 (16%) or both negative in 35 (82%) out of 43 patients successfully included in the study. NP-swabs and saliva results did not perfectly match in one patient (saliva positive, NP-swab negative). Positive molecular results were significantly associated with disease duration (p = 0.0049). 326/326 screening subjects were SARS-CoV-2 negative on both NP-swabs and saliva. Among the 27 saliva samples tested for IgA, 18 were IgA positive. Salivary IgA positivity was associated with pneumonia (p = 0.002) and CRP values (p = 0.0183), not with other clinical and molecular data, or with serum immunoglubulins.
A standardized saliva collection can be adopted to detect SARS-CoV-2 infection in alternative to NP-swabs. Preliminary data on salivary IgA support the use of saliva also for patient monitoring.
The prognosis of multiple myeloma is mainly dependent upon chromosomal changes. The 2 major abnormalities driving poor outcome are del(17p) and t(4;14). However, the outcome of these high-risk ...patients is not absolutely uniform, with some patients presenting long survival. We hypothesized that these better outcomes might be related to concomitant “good-risk” chromosomal changes exploring hyperdiploidy. We analyzed a large series of 965 myeloma patients, including 168 patients with t(4;14) and 126 patients with del(17p), using high-throughput single-nucleotide polymorphism arrays after plasma cell sorting. As expected, trisomic chromosomes were highly associated. Using the LASSO model, we found that only chromosome 3, when trisomic, was associated with a longer progression-free survival and that 3 trisomies modulated overall survival (OS) in myeloma patients: trisomies 3 and 5 significantly improved OS, whereas trisomy 21 worsened OS. In patients with t(4;14), trisomies 3 and/or 5 seemed to overcome the poor prognosis. For the first time, using a specific modeling approach, we show that not all trisomies display the same prognostic impact. This finding could be important for routine assessment of prognosis in myeloma, and some high-risk patients with a traditional evaluation could in fact be standard-risk patients.
•In myeloma patients, trisomy 3 improved time to progression and trisomies 3 and/or 5 improved overall survival.•In contrast, trisomy 21 significantly worsened overall survival.
In multiple myeloma, cytogenetic changes are important predictors of patient outcome. In this setting, the most important changes are deletion 17p, del(17p), and translocation of chromosomes 4 and ...14, t(4;14), conferring a poor outcome. However, a certain degree of heterogeneity is observed in the survival of these high-risk patients. We hypothesized that other chromosomal changes may impact the outcome. We retrospectively analyzed a large series of 242 patients displaying either t(4;14) (157 patients) or del(17p) (110 patients), 25 patients presenting both abnormalities, using single nucleotide polymorphism array. In patients with t(4;14), del(1p32), del22q, and >30 chromosomal structural changes negatively impacted progression-free survival (PFS). For overall survival (OS), del(13q14), del(1p32), and the number of chromosomal structural changes worsened the prognosis of patients. For patients with del(17p), del6q worsened the prognosis of patients, whereas trisomy 15 and monosomy 14 were found to have a protective effect on PFS. For OS, del(1p32) worsened the prognosis of patients, whereas having >8 numerical changes was found to have a protective effect on survival. This study, which is the largest series of high-risk patients analyzed with the most modern genomic technique, identified 1 main factor negatively impacting survival: del(1p32).
•Additional chromosomal changes modulate the outcome of patients with high-risk multiple myeloma.
Ataxia‐telangiectasia‐like disorder (ATLD) is a rare genomic instability syndrome caused by biallelic variants of MRE11 (meiotic recombination 11) characterized by progressive cerebellar ataxia and ...typical karyotype abnormalities. These symptoms are common to those of ataxia‐telangiectasia, which is consistent with the key role of MRE11 in ataxia‐telangiectasia mutated (ATM) activation after DNA double‐strand breaks. Three unrelated French patients were referred with ataxia. Only one had typical karyotype abnormalities. Unreported biallelic MRE11 variants were found in these three cases. Interestingly, one variant (c.424G>A) was present in two cases and haplotype analysis strongly suggested a French founder variant. Variants c.544G>A and c.314+4_314+7del lead to splice defects. The level of MRE11 in lymphoblastoid cell lines was consistently and dramatically reduced. Functional consequences were evaluated on activation of the ATM pathway via phosphorylation of ATM targets (KAP1 and CHK2), but no consistent defect was observed. However, an S‐phase checkpoint activation defect after camptothecin was observed in these patients with ATLD. In conclusion, we report the first three French ATLD patients and a French founder variant, and propose an S‐phase checkpoint activation study to evaluate the pathogenicity of MRE11 variants.
Ataxia‐Telangiectasia‐Like Disorder (ATLD) is a rare genomic instability syndrome caused by biallelic variants of MRE11 (meiotic recombination 11) characterized by progressive cerebellar ataxia. We describe the first three French patients with progressive cerebellar ataxia diagnosed with ATLD, associated with compound heterozygosity for unreported MRE11 variants. Functional consequences were evaluated on activation of the ataxia‐telangiectasia mutated (ATM) pathway via phosphorylation of ATM targets, but no consistent defect was observed. However, an S‐phase checkpoint activation defect after camptothecin was observed in these ATLD patients.
Nijmegen breakage syndrome caused by biallelic pathogenic variants of the DNA‐damage response gene NBN, is characterized by severe microcephaly, cancer proneness, infertility, and karyotype ...abnormalities. We previously reported NBN variants in siblings suffering from fertility defects. Here, we identify a new founder NBN variant (c.442A>G, p.(Thr148Ala)) in Lebanese patients associated with isolated infertility. Functional analyses explored preserved or altered functions correlated with their remarkably mild phenotype. Transcript and protein analyses supported the use of an alternative transcript with in‐frame skipping of exons 4–5, leading to p84‐NBN protein with a preserved forkhead‐associated (FHA) domain. The level of NBN was dramatically reduced and the MRN complex delocalized to the cytoplasm. Interestingly, ataxia–elangiectasia mutated (ATM) also shifted from the nucleus to the cytoplasm, suggesting some interaction between ATM and the MRN complex at a steady state. The ATM pathway activation, attenuated in typical patients with NBS, appeared normal under camptothecin treatment in these new NBN‐related infertile patients. Cell cycle checkpoint defect was present in these atypical patients, although to a lesser extent than in typical patients with NBS. In conclusion, we report three new NBN‐related infertile patients and we suggest that preserved FHA domain could be responsible for the mild phenotype and intermediate DNA‐damage response defects.
Next-generation sequencing (NGS) is routinely used for constitutional genetic analysis. However, cross-contamination between samples constitutes a major risk that could impact the results of the ...analysis. We have developed ART-DeCo, a tool using the allelic ratio (AR) of the Single Nucleotide Polymorphisms sequenced with regions of interest. When a sample is contaminated by DNA with a different genotype, unexpected ARs are obtained, which are in turn used for detection of contamination with a screening test, followed by identification and quantification of the contaminant. Following optimization, ART-DeCo was applied to 2222 constitutional DNA samples. The screening test was positive for 191 samples. In 33 cases (contamination percentages: 1.3% to 29.2%), the contaminant was identified and was mostly located in adjacent wells. Three other positive cases were due to barcoding errors or mixture of two DNA samples. Interestingly, the last contaminated sample corresponded to a bone marrow transplant recipient. Lastly, no contaminant was identified in 154 weakly positive ( < 4%) samples that were considered to be irrelevant to constitutional genetic analysis. ART-DeCo lends itself to mandatory quality control procedures, also highlighting the delicate steps of library preparation, resulting in practice improvement. Importantly, ART-DeCo can be implemented in any NGS workflow, from gene panel to genome-wide analyses. https://sourceforge.net/projects/ngs-art-deco/ .
Background/Objectives: Endometriosis is a female chronic inflammatory disease in which endometrial tissue develops outside the uterine cavity. It is a complex pathology, which significantly ...contributes to morbidity in premenopausal women, leading to chronic pain, infertility, and subfertility negatively impacting physical and emotional well-being and the overall quality of life. The public health burden of endometriosis remains elusive and challenging to determine, and this uncertainty can lead to inadequate healthcare services and treatments. The objective was to estimate the incidence and prevalence of endometriosis in Italy using the hospital discharge records database via a population-based retrospective study, nationwide between 2011 and 2020. Methods: From the National Hospital Discharge Database, we selected all admissions with a diagnosis of endometriosis (ICD-9-CM, codes 617.x), supported by the presence of a procedure code of laparoscopy or any other surgical procedure allowing for direct visualisation of the lesions. The main outcomes measured: incidence and prevalence of endometriosis were estimated for the entire 2011–2020 period and by individual year, analysing the time trend and variability in different geographical areas of Italy. Results: There were a total of 134,667,646 women aged 15–50 years with one or more hospitalisations for endometriosis in all Italian hospitals. The incidence of endometriosis in Italy during this period was 0.839 per 1000 women (CI95% 0.834–0.844), exhibiting a statistically significant decreasing trend over the years. A discernible north–south gradient was observed, with higher rates documented in the northern regions. The prevalence rate stood at 14.0 per 1000 during the same period, and a similar north–south geographical gradient was identifiable in the prevalence rates as well. Conclusions: The utilization of national-level hospital data enables the generation of incidence and prevalence data for endometriosis without variations in methods and definitions, facilitating the evaluation of temporal trends and regional comparisons. Understanding and quantifying this phenomenon is essential for appropriate healthcare planning in various Italian regions.
We discuss optimizations of pinned photodiode (PPD) pixels for indirect time of flight sensors. We focus on the transfer-gate and dumping gate regions optimization, on the PPD dimension and shape to ...assure fast lateral charge transfer and on the epitaxial layer thickness for a good tradeoff between fast vertical charge transfer and high quantum efficiency at near infrared region. The overall performance of the pixel is quantified by the demodulation contrast of the pixel at specific frequencies. The operation frequency of the device is determined by the required ambiguity range of the application and the required distance noise. In order to reach a reasonable distance noise, the pixel needs to allow modulation frequencies up to 100 MHz. In this paper, we present TCAD simulation and experimental data on demodulation contrast, impulse response time, and quantum efficiency of 10 × 10 μm pixels. We introduce a setup for impulse response measurement and we compare this to the demodulation contrast. We also discuss the optimization of the dump gate and dump diffusion. With the best pixel we measured a quantum efficiency of about 45% at 850 nm, a demodulation contrast of 47% at 80 MHz, and an impulse response time <; 5 ns.
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