The precise link between inflammation and pathogenesis of myelodysplastic syndrome (MDS) is yet to be fully established. We developed a novel method to measure ASC/NLRP3 protein specks which are specific for the NLRP3 inflammasome only. We combined this with cytokine profiling to characterise various inflammatory markers in a large cohort of patients with lower risk MDS in comparison to healthy controls and patients with defined autoinflammatory disorders (AIDs). The ASC/NLRP3 specks were significantly elevated in MDS patients compared to healthy controls (p < 0.001) and these levels were comparable to those found in patients with AIDs. The distribution of protein specks positive only for ASC was different to ASC/NLRP3 ones suggesting that other ASC-containing inflammasome complexes might be important in the pathogenesis of MDS. Patients with MDS-SLD had the lowest levels of interleukin (IL)-1β, tumour necrosis factor (TNF), IL-23, IL-33, interferon (IFN) γ and IFN-α2, compared to other diagnostic categories. We also found that inflammatory cytokine TNF was positively associated with MDS progression to a more aggressive form of disease and IL-6 and IL-1β with time to first red blood cell transfusion. Our study shows that there is value in analysing inflammatory biomarkers in MDS, but their diagnostic and prognostic utility is yet to be fully validated.
- Klíčová slova
- MDS, NLRP3 inflammasome, cytokines, inflammation,
- Publikační typ
- časopisecké články MeSH
PURPOSE: Posterior corneal vesicles (PCVs) have clinical features that are similar to posterior polymorphous corneal dystrophy (PPCD). To help determine whether there is a shared genetic basis, we screened 38 individuals with PCVs for changes in the three genes identified as causative for PPCD. METHODS: We prospectively recruited patients for this study. We examined all individuals clinically, with their first-degree relatives when available. We used a combination of Sanger and exome sequencing to screen regulatory regions of OVOL2 and GRHL2, and the entire ZEB1 coding sequence. RESULTS: The median age at examination was 37.5 years (range 4.7-84.0 years), 20 (53%) were male and in 19 (50%) the PCVs were unilateral. Most individuals were discharged to optometric review, but five had follow-up for a median of 12 years (range 5-13 years) with no evidence of progression. In cases with unilateral PCVs, there was statistically significant evidence that the change in the affected eye was associated with a lower endothelial cell density (p = 0.0003), greater central corneal thickness (p = 0.0277) and a steeper mean keratometry (p = 0.0034), but not with a higher keratometric astigmatism or a reduced LogMAR visual acuity. First-degree relatives of 13 individuals were available for examination, and in 3 (23%), PCVs were identified. No possibly pathogenic variants were identified in the PPCD-associated genes screened. CONCLUSION: We found no evidence that PCVs share the same genetic background as PPCD. In contrast to PPCD, we confirm that PCVs is a mild, non-progressive condition with no requirement for long-term review. However, subsequent cataract surgery can lead to corneal oedema.
- Klíčová slova
- GRHL2, OVOL2, ZEB1, cornea, corneal endothelium,
- MeSH
- astigmatismus * MeSH
- dědičné dystrofie rohovky * diagnóza genetika MeSH
- dítě MeSH
- dospělí MeSH
- edém rohovky * MeSH
- lidé středního věku MeSH
- lidé MeSH
- mladiství MeSH
- mladý dospělý MeSH
- předškolní dítě MeSH
- rohovka patologie MeSH
- senioři nad 80 let MeSH
- senioři MeSH
- transkripční faktory genetika MeSH
- Check Tag
- dítě MeSH
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mladiství MeSH
- mladý dospělý MeSH
- mužské pohlaví MeSH
- předškolní dítě MeSH
- senioři nad 80 let MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- Názvy látek
- Ovol2 protein, human MeSH Prohlížeč
- transkripční faktory MeSH
AIMS AND OBJECTIVES: The aim of this study was to describe the prevalence of low back pain (LBP) and the use of lifting aids and ergonomics among Czech registered nurses. BACKGROUND: Low back pain is the most common occupational health problem affecting nurses. Frequent manual lifting of heavy loads, including patients, is one of the main duties of nursing staff, which causes compressive and shear forces on the vertebrae of the lower spine. Training in manual handling and lifting aids reduce the physical burden on the musculoskeletal system, thus decreasing work-related back injuries and further back problems. DESIGN: A cross-sectional survey. METHODS: The online survey was distributed to 1460 randomly selected nurses involved in caring for patients. The survey comprised the extended version of the Nordic Musculoskeletal Questionnaire and a self-structured questionnaire. Data were analysed using STATA 15 at a significance level of 0.05. RESULTS: Of the 569 respondents, 84.7% reported high occurrence of LBP over the previous 12-month period. The lower back was the most commonly reported body region for pain, followed by the neck, shoulders and upper back. LBP was found to occur significantly less among nursing staff who used mechanical lifting aids. Nurses with a higher level of education were found significantly more likely to use mechanical patient-lifting equipment in their clinical practice. CONCLUSIONS: The study findings show that LBP is a frequent problem among nurses and has highlighted a lack of organisational safety practices and culture in clinical nursing practice. RELEVANCE TO CLINICAL PRACTICE: This study provides valuable information about the extent of LBP among nurses with insufficient preventive measures or health and safety practices at work. The results provide useful baseline data for the Czech Republic, that may lead to increased awareness and therefore implementation of preventative strategies, and thus enable a reduction in the risk of back injuries among nursing professionals.
- Klíčová slova
- ergonomics, health risks, musculoskeletal, pain, registered nurses, survey,
- MeSH
- lidé MeSH
- lumbalgie * epidemiologie MeSH
- nemoci z povolání * epidemiologie MeSH
- prevalence MeSH
- průřezové studie MeSH
- průzkumy a dotazníky MeSH
- rizikové faktory MeSH
- zdravotní sestry * MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- Geografické názvy
- Česká republika MeSH
OBJECTIVE: We aimed to evaluate the validity of a MARSIPAN-guidance-adapted Early Warning System (MARSI MEWS) and compare it to the National Early Warning Score (NEWS) and an adapted version of the Physical Risk in Eating Disorders Index (PREDIX), to ascertain whether current practice is comparable to best-practice standards. METHODS: We collated 3,937 observations from 36 inpatients from Addenbrookes Hospital over 2017-2018 and used three independent raters to create a "gold standard" of deteriorating cases. We ascertained performance metrics (Receiver Operating Characteristic Area Under the curve) for MARSI MEWS, NEWS and PREDIX; we also tested the proof of concept of a machine-learning-based early-warning-system (ML-EWS) using cross-validation and out-of-sample prediction of cases. RESULTS: The MARSI MEWS system showed higher ROC AUC (0.916) compared to NEWS (0.828) or PREDIX (0.865). ML-EWS (random forest) performed well at independent samples analysis (0.980) and multilevel analysis (0.922). CONCLUSION: MARSI MEWS seems most suitable for identifying critically deteriorating cases in anorexia nervosa inpatient population. We did not examine community practice in which the PREDIX arguably remains the best to ascertain deteriorating cases. Our results also provide a first proof of concept for the development of artificial-intelligence-based early warning systems in anorexia nervosa. Implications for inpatient clinical practice in eating disorders are discussed.
- Klíčová slova
- anorexia nervosa, deterioration, early warning system, inpatient, machine learning,
- MeSH
- časná diagnóza * MeSH
- dospělí MeSH
- hospitalizace * MeSH
- klinické zhoršení * MeSH
- lidé MeSH
- mentální anorexie terapie MeSH
- monitorování fyziologických funkcí metody MeSH
- plocha pod křivkou MeSH
- reprodukovatelnost výsledků MeSH
- ROC křivka MeSH
- systém včasného varování MeSH
- Check Tag
- dospělí MeSH
- lidé MeSH
- mužské pohlaví MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- pozorovací studie MeSH
- práce podpořená grantem MeSH
BACKGROUND: Despite a myriad of attempts in the last three decades to diagnose ovarian cancer (OC) earlier, this clinical aim still remains a significant challenge. Aberrant methylation patterns of linked CpGs analyzed in DNA fragments shed by cancers into the bloodstream (i.e. cell-free DNA) can provide highly specific signals indicating cancer presence. METHODS: We analyzed 699 cancerous and non-cancerous tissues using a methylation array or reduced representation bisulfite sequencing to discover the most specific OC methylation patterns. A three-DNA-methylation-serum-marker panel was developed using targeted ultra-high coverage bisulfite sequencing in 151 women and validated in 250 women with various conditions, particularly in those associated with high CA125 levels (endometriosis and other benign pelvic masses), serial samples from 25 patients undergoing neoadjuvant chemotherapy, and a nested case control study of 172 UKCTOCS control arm participants which included serum samples up to two years before OC diagnosis. RESULTS: The cell-free DNA amount and average fragment size in the serum samples was up to ten times higher than average published values (based on samples that were immediately processed) due to leakage of DNA from white blood cells owing to delayed time to serum separation. Despite this, the marker panel discriminated high grade serous OC patients from healthy women or patients with a benign pelvic mass with specificity/sensitivity of 90.7% (95% confidence interval [CI] = 84.3-94.8%) and 41.4% (95% CI = 24.1-60.9%), respectively. Levels of all three markers plummeted after exposure to chemotherapy and correctly identified 78% and 86% responders and non-responders (Fisher's exact test, p = 0.04), respectively, which was superior to a CA125 cut-off of 35 IU/mL (20% and 75%). 57.9% (95% CI 34.0-78.9%) of women who developed OC within two years of sample collection were identified with a specificity of 88.1% (95% CI = 77.3-94.3%). Sensitivity and specificity improved further when specifically analyzing CA125 negative samples only (63.6% and 87.5%, respectively). CONCLUSIONS: Our data suggest that DNA methylation patterns in cell-free DNA have the potential to detect a proportion of OCs up to two years in advance of diagnosis and may potentially guide personalized treatment. The prospective use of novel collection vials, which stabilize blood cells and reduce background DNA contamination in serum/plasma samples, will facilitate clinical implementation of liquid biopsy analyses.
- Klíčová slova
- Cell-free DNA, DNA methylation, Early diagnosis, Ovarian cancer, Personalized treatment, Screening, Serum DNA,
- MeSH
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- metylace DNA * MeSH
- nádorové biomarkery krev genetika normy MeSH
- nádory vaječníků krev genetika MeSH
- náhodné rozdělení MeSH
- sekvenční analýza DNA metody normy MeSH
- senioři MeSH
- volné cirkulující nukleové kyseliny genetika MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- hodnotící studie MeSH
- práce podpořená grantem MeSH
- Názvy látek
- nádorové biomarkery MeSH
- volné cirkulující nukleové kyseliny MeSH
