Abstract
Background
The modified Rutgeerts’ score (mRS) is widely used for the assessment of endoscopic postoperative recurrence (ePOR) in Crohn’s disease (CD) after ileocolic resection to guide ...therapeutic decisions. To improve the validity and prognostic value of this endoscopic assessment, two new scores have been proposed. This study assessed the interobserver agreement of the current (mRS) and new endoscopic scores for ePOR in CD.
Methods
Sixteen academic and non-academic IBD specialists assessed endoscopic videos (n=71) of postoperative CD patients (n=66) retrieved from nine Dutch centers. Each video was assessed for the degree of inflammation by four gastroenterologists using the mRS, REMIND score (separate score of anastomosis and neoterminal ileum) and anatomic score (separate score of lesions at the anastomotic line, ileal body, ileal inlet, neoterminal ileum, colonic and/or ileal blind loop). Interobserver agreement was assessed using Fleiss’ weighted kappa.
Results
Fleiss’ weighted kappa for the mRS was 0.67 (95% confidence interval CI 0.59–0.74). The weighted kappa for the REMIND score was 0.73 (95% CI 0.65–0.80) for lesions in the neoterminal ileum and 0.46 (95% CI 0.35–0.58) for anastomotic lesions. In the anatomic score, the weighted kappa for lesions in the ileal body, ileal inlet, neoterminal ileum, colonic and ileal blind loop was 0.61 (95% CI 0.49–0.73), 0.63 (95% CI 0.54–0.72), 0.61 (95% CI 0.49–0.74), 0.83 (95% CI 0.62–1.00) and 0.68 (95% CI 0.46–0.89), and 0.44 (95% CI 0.32–0.55) for lesions at the anastomotic line.
Conclusion
The interobserver agreement of the mRS is substantial. Similarly, the interobserver agreement is substantial for lesions in the neoterminal ileum according to both the REMIND and anatomic score, whereas only moderate for anastomotic lesions. Since therapeutic decisions in clinical practice are based on these assessments and these scores are used as outcome measure in clinical studies, further improvement of agreement is essential.
Abstract only Introduction: Injury to the corticospinal tract (CST) has been shown to have a major effect on upper extremity motor recovery after stroke. This study aimed to examine how well CST ...injury, measured from neuroimaging acquired during the acute stroke workup, predicts upper extremity motor recovery. Methods: Patients (N = 48) with upper extremity weakness after ischemic stroke were assessed using the upper extremity Fugl-Meyer (FM) during the acute stroke hospitalization and again at 3-month follow-up. CST injury was quantified and compared, using four different methods, from images obtained as part of the stroke standard-of-care workup. Logistic and linear regression were performed using CST injury to predict delta FM. Injury to primary motor and premotor cortices were included as potential modifiers of the effect of CST injury on recovery. Results: 48 patients were enrolled 4.2 ± 2.7 days post-stroke and completed this study. CST injury distinguished patients who reached their recovery potential (as predicted from initial impairment) from those who did not, with AUC values ranging from 0.75 to 0.8. In addition, CST injury explained ~20% of the variance in the magnitude of upper extremity recovery, even after controlling for the severity of initial impairment. Results were consistent when comparing four different methods of measuring CST injury. Extent of injury to primary motor and premotor cortices did not significantly influence the predictive value that CST injury had for recovery. Conclusions: Structural injury to the CST, as estimated from standard-of-care imaging available during the acute stroke hospitalization, is a robust way to distinguish patients who achieve their predicted recovery potential and explains a significant amount of the variance in post-stroke upper extremity motor recovery.
Dense localized blooms of the toxic dinoflagellate Alexandrium ostenfeldii are a recent phenomenon in the low salinity waters of the Baltic Sea. This study reports results from laboratory experiments ...investigating the interaction between PSP toxin producing strains of A. ostenfeldii and two copepod species, Eurytemora affinis and Acartia bifilosa, from the northern Baltic Sea. Copepod grazing rates were studied by incubating the copepods with mixed cultures of A. ostenfeldii isolated from a bloom area. The effect of A. ostenfeldii on copepod condition and behavior was studied by exposing copepods to the mixed cultures and cell-free filtrates. Grazing on A. ostenfeldii cells was negligible for both copepod species. The 24 h incapacitation incubations indicated that the condition of both copepod species was negatively affected by the presence of A. ostenfeldii. The behavioral changes observed took place during the first hours of exposure to A. ostenfeldii cells, and little or no change was observed in the condition of the copepods after 6 h compared to 24 h. Similar observations were made for E. affinis incubated in cell-free filtrates of A. ostenfeldii, while the response of A. bifilosa was less pronounced. Our study shows that the copepods do not graze on A. ostenfeldii due to rapid behavioral disturbance and incapacitation by the algal cells and their exudates. This represents the first observation of a negative effect of the A. ostenfeldii on co-occurring biota in the northern Baltic Sea.
Abstract Aim Stereotactic body radiation therapy (SBRT) is increasingly used as an option for those with liver metastases. In order to facilitate future economic impact of health technologies, health ...utility scores may be used. The EuroQOL-5D-3L (EQ-5D) preference-based healthy utility instrument was used to evaluate the impact of treatment with SBRT on health utility scores. Materials and methods Between August 2013 and October 2014, 31 patients treated with 3–5 fractions of SBRT for liver metastases were enrolled in this study. The EQ-5D instrument was administered at baseline, during and up to 6 months post-SBRT. Results Mean EQ-5D score at baseline was 0.857, which remained stable across the entire study time period. Transient increases in difficulties with mobility (9.7% reported at baseline to 16.1% on the last day of treatment) and usual activities (3.2% reported at baseline to 34.5% on day two) were found during the course of treatment; these returned to baseline levels subsequently. The mean visual analogue score at baseline was 65.8 and remained unchanged throughout treatment and follow-up. Conclusions The stability of health utility scores and problems reported by patients undergoing treatment indicate that SBRT for liver metastases does not impart a significant adverse effect on quality of life. These results may be used for future economic evaluation of SBRT.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK, ZRSKP
Summary
Liver transplantation for primary sclerosing cholangitis (PSC) can be complicated by recurrence of PSC (rPSC). This may compromise graft survival but the effect on patient survival is less ...clear. We investigated the effect of post‐transplant rPSC on graft and patient survival in a large European cohort. Registry data from the European Liver Transplant Registry regarding all first transplants for PSC between 1980 and 2015 were supplemented with detailed data on rPSC from 48 out of 138 contributing transplant centres, involving 1,549 patients. Bayesian proportional hazards models were used to investigate the impact of rPSC and other covariates on patient and graft survival. Recurrence of PSC was diagnosed in 259 patients (16.7%) after a median follow‐up of 5.0 years (quantile 2.5%‐97.5%: 0.4–18.5), with a significant negative impact on both graft (HR 6.7; 95% CI 4.9–9.1) and patient survival (HR 2.3; 95% CI 1.5–3.3). Patients with rPSC underwent significantly more re‐transplants than those without rPSC (OR 3.6, 95% CI 2.7–4.8). PSC recurrence has a negative impact on both graft and patient survival, independent of transplant‐related covariates. Recurrence of PSC leads to higher number of re‐transplantations and a 33% decrease in 10‐year graft survival.
Recurrence of PSC negatively impacts both graft and patient survival–an European Liver Transplant Registry study
This Science White Paper, prepared in response to the ESA Voyage 2050 call for long-term mission planning, aims to describe the various science possibilities that can be realized with an L-class ...space observatory that is dedicated to the study of the interactions of cosmic microwave background (CMB) photons with the cosmic web. Our aim is specifically to use the CMB as a backlight – and survey the gas, total mass, and stellar content of the entire observable Universe by means of analyzing the spatial and spectral distortions imprinted on it. These distortions result from two major processes that impact on CMB photons: scattering by free electrons and atoms (Sunyaev-Zeldovich effect in diverse forms, Rayleigh scattering, resonant scattering) and deflection by gravitational potential (lensing effect). Even though the list of topics collected in this White Paper is not exhaustive, it helps to illustrate the exceptional diversity of major scientific questions that can be addressed by a space mission that will reach an angular resolution of 1.5 arcmin (goal 1 arcmin), have an average sensitivity better than 1 μK-arcmin, and span the microwave frequency range from roughly 50 GHz to 1 THz. The current paper also highlights the synergy of our Backlight mission concept with several upcoming and proposed ground-based CMB experiments.
Pemphigus is a group of bullous diseases characterized by acantholysis and skin blisters. As for other autoimmune diseases, the strongest genetic associations found so far for pemphigus foliaceus ...(PF) and vulgaris (PV) are with alleles of HLA genes. However, apart from protein-coding genes, the MHC region includes a set of poorly explored long non-coding RNA (lncRNA) genes, the HLA complex group (HCG).
To investigate if HCG lncRNA alleles are associated with pemphigus susceptibility.
We analyzed SNPs in 13 HCG lncRNA genes, both in PV (Germany: 241 patients; 1,188 controls) and endemic PF (Brazil: 227 patients; 194 controls), applying multivariate logistic regression. We found 55 associations with PV (pcorr < 0.01) and nine with endemic PF (pcorr < 0.05), the majority located in TSBP1-AS1 (which includes HCG23) and HCG27 lncRNA genes, independently of HLA alleles previously associated with pemphigus. The association of TSBP1-AS1 rs3129949*A allele was further replicated in sporadic PF (p = 0.027, OR = 0.054; 75 patients and 150 controls, all from Germany). Next, we evaluated the expression levels of TSBP1-AS1, TSBP1, HCG23, and HCG27 in blood mononuclear cells of Brazilian patients and controls. HCG27 was upregulated in endemic PF (p = 0.035, log2 FC = 1.3), while TSBP1-AS1 was downregulated in PV (p = 0.029, log2 FC = −1.29). The same expression patterns were also seen in cultured keratinocytes stimulated with IgG antibodies from patients and controls from Germany. TSBP1 mRNA levels were also decreased in endemic PF blood cells (p = 0.042, log2 FC = −2.14). TSBP1-AS1 and HCG27 were also observed downregulated in CD19+ cells of endemic PF (p < 0.01, log2 FC = −0.226 and −0.46 respectively).
HCG lncRNAs are associated with susceptibility to pemphigus, being TSBP1-AS1 and HCG27 also differentially expressed in distinct cell populations. These results suggest a role for HCG lncRNAs in pemphigus autoimmunity.
•This is the first association study investigating the whole set of HLA-Complex Group (HCG) long non-coding RNAs (lncRNAs).•TSBP1-AS1 (which includes HCG23) and HCG27 are the most strongly associated genes with pemphigus.•TSBP1-AS1 rs3129949*A allele is also associated with sporadic PF.•The HCG associations are independent of HLA alleles.•TSBP1-AS1 and HCG27 are differentially expressed in pemphigus vulgaris and pemphigus foliaceus (respectively).
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Genetic variations mapping to 3′ untranslated regions (3′UTRs) may overlap with microRNA (miRNA) binding sites, therefore potentially interfering with translation inhibition or messenger RNA (mRNA) ...degradation. The aim of this study was to investigate whether single nucleotide polymorphisms (SNPs) located within the 3′UTRs of six candidate genes and predicted to interfere with miRNA ligation could account for disease-relevant differential mRNA levels. Focusing on pemphigus foliaceus (PF) – an autoimmune blistering skin condition with unique endemic patterns – we investigated whether nine 3′UTR SNPs from the CD1D, CTLA4, KLRD1, KLRG1, NKG7, and TNFSF13B genes differentially expressed in PF were disease-associated. The heterozygous genotype of the KLRG1 rs1805672 polymorphism was associated with increased predisposition to PF (A/G vs. A/A: P=0.038; OR=1.60), and a trend for augmented susceptibility was observed for carriers of the G allele (P=0.094; OR=1.44). In silico analyses suggested that rs1805672 G allele could disrupt binding of miR-584-5p, and indicated rs1805672 as an expression Quantitative Trait Locus (eQTL), with an effect on KLRG1 gene expression. Dual-luciferase assay showed that miR-584-5p mediated approximately 50% downregulation of the reporter gene's activity through the 3′UTR of KLRG1 harboring rs1805672 A allele (vs. miRNA-negative condition, P=0.006). This silencing relationship was lost after site-directed mutation to G allele (vs. miRNA-negative condition, P=0.391; vs. rs1805672 A allele, P=0.005). Collectively, these results suggest that a disease-associated SNP located within the 3′UTR of KLRG1 directly interferes with miR-584-5p binding, allowing for KLRG1 mRNA differential accumulation, which in turn may contribute to pathogenesis of autoimmune diseases, such as pemphigus.
•The KLRG1 rs1805672 G allele may increase susceptibility to pemphigus foliaceus.•A molecular mechanism is proposed for G allele-dependent miR-584-5p binding loss.•The G allele abrogates reduction of reporter levels with KLRG1 3′UTR and miR-584-5p.•rs1805672 shows an expression Quantitative Trait Locus effect on KLRG1 expression.•Higher levels of KLRG1 in the disease may relate to rs1805672 miR-disrupting effect.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK, ZRSKP
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