994 research outputs found
Vedolizumab for Inflammatory Bowel Disease:Two-Year Results of the Initiative on Crohn and Colitis (ICC) Registry, A Nationwide Prospective Observational Cohort Study: ICC Registry - Vedolizumab
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220028.pdf (Publisherâs version ) (Open Access)Prospective data of vedolizumab treatment for patients with inflammatory bowel disease (IBD) beyond 1 year of treatment is scarce but needed for clinical decision making. We prospectively enrolled 310 patients with IBD (191 with Crohn's disease (CD) and 119 patients with ulcerative colitis (UC)) with a follow-up period of 104 weeks (interquartile range: 103-104) in a nationwide registry. The corticosteroid-free clinical remission rate (Harvey Bradshaw Index â€Â 4, Short Clinical Colitis Activity index â€Â 2) at weeks 52 and 104 were 28% and 19% for CD and 27% and 28% for UC, respectively. Fifty-nine percent maintained corticosteroid-free clinical remission between weeks 52 and 104. Vedolizumab with concomitant immunosuppression showed comparable effectiveness outcomes compared with vedolizumab monotherapy (week 104: 21% vs. 23%; P = 0.77), whereas 8 of 13 severe infections occurred in patients treated with concomitant immunosuppression. To conclude, the clinical effect was 19% for CD and 28% for UC after 2 years of follow-up regardless of concomitant immunosuppression
GEMS: Galaxy Evolution from Morphologies and SEDs
GEMS, Galaxy Evolution from Morphologies and SEDs, is a large-area (800
arcmin2) two-color (F606W and F850LP) imaging survey with the Advanced Camera
for Surveys on HST. Centered on the Chandra Deep Field South, it covers an area
of ~28'x28', or about 120 Hubble Deep Field areas, to a depth of
m_AB(F606W)=28.3 (5sigma and m_AB(F850LP)=27.1 (5sigma) for compact sources. In
its central ~1/4, GEMS incorporates ACS imaging from the GOODS project.
Focusing on the redshift range 0.2<=z<=1.1, GEMS provides morphologies and
structural parameters for nearly 10,000 galaxies where redshift estimates,
luminosities and SEDs exist from COMBO-17. At the same time, GEMS contains
detectable host galaxy images for several hundred faint AGN. This paper
provides an overview of the science goals, the experiment design, the data
reduction and the science analysis plan for GEMS.Comment: 24 pages, TeX with 6 eps Figures; to appear in ApJ Supplement. Low
resolution figures only. Full resolution at
http://zwicky.as.arizona.edu/~rix/Misc/GEMS.ps.g
The effect of induction therapy with infliximab or vedolizumab on hepcidin and iron status in patients with Inflammatory Bowel Disease
Background Differentiating absolute iron deficiency from functional iron restriction is challenging in active Inflammatory Bowel Disease (IBD). Hepcidin, the systemic iron regulator, could be the key in the diagnosis and management of absolute iron deficiency. In this study, we assessed hepcidin as a diagnostic iron deficiency marker and we explored the relationship between hepcidin, inflammation, hypoxia, and iron deficiency in patients receiving induction therapy with infliximab (IFX) or vedolizumab (VEDO). Methods 130 patients with IBD, who received induction therapy with IFX or VEDO for active disease, were included in this study. Clinical and biochemical data were extracted from medical records. Serum samples at baseline and week 6 of induction therapy were retrieved from the University Medical Center Groningen (UMCG) biobank and analysed for: hepcidin, inflammation (e.g., interleukins [IL] 6, 10, and Tumour Necrosis Factor-α [TNFα]), oxidative stress (free thiols), and hypoxia (e.g., erythropoietin [EPO], Macrophage Inflammatory Protein-3α [MIP3α]). For comparison, serum samples from 50 age- and gender-matched healthy controls were obtained from pre-donation biobank at the UMCG. Response to therapy was defined by either General Physicianâs Assessment at week 14 of induction therapy, normalisation or at least a three-point decrease in clinical scores: Harvey-Bradshaw Index (HBI) for Crohnâs Disease, Simple Clinical Colitis Activity Index (SCCAI) for ulcerative colitis. Results Hepcidin correlated with ferritin and sTfR/log ferritin index [Ï = 0.74 and Ï = -0.79, respectively; P<0.001 for both markers], while inflammation- and hypoxia-associated markers showed only marginal correlations. Hepcidin accurately identified absolute iron deficiency: AUC(hepcidin) = 0.89 [95% CI: 0.82â0.95; P<0.001]. Induction with either IFX or VEDO decreased hepcidin [13.5 ng/mL vs. 9.5 ng/mL; P<0.001], ferritin [45.5 ug/L vs. 37.0 ug/L, P<0.05], and inflammatory markers at week 6, while transferrin increased [2.4 g/L vs. 2.5 g/L, P<0.001]. In total, 75.4% of patients responded to the induction therapy. Hepcidin and ferritin decreased, while transferrin increased (P<0.001 for all changes) in patients who responded to the therapy. In addition, hypoxia (EPO and MIP3α) and inflammatory markers such as faecal calprotectin, IL-6, IL-22, and TNFα improved significantly. In contrast, none of these improvements were observed in patients who did not respond to the therapy. Conclusion Hepcidin reflects iron deficiency in active IBD, but inflammation masks the severity of the deficiency. Induction therapy with either IFX or VEDO modulates hepcidin and iron indices, especially in patients who respond to the therapy
Hereditary cancer registries improve the care of patients with a genetic predisposition to cancer:contributions from the Dutch Lynch syndrome registry
The Dutch Hereditary Cancer Registry was established in 1985 with the support of the Ministry of Health (VWS). The aims of the registry are: (1) to promote the identification of families with hereditary cancer, (2) to encourage the participation in surveillance programs of individuals at high risk, (3) to ensure the continuity of lifelong surveillance examinations, and (4) to promote research, in particular the improvement of surveillance protocols. During its early days the registry provided assistance with family investigations and the collection of medical data, and recommended surveillance when a family fulfilled specific diagnostic criteria. Since 2000 the registry has focused on family follow-up, and ensuring the quality of surveillance programs and appropriate clinical management. Since its founding, the registry has identified over 10,000 high-risk individuals with a diverse array of hereditary cancer syndromes. All were encouraged to participate in prevention programmes. The registry has published a number of studies that evaluated the outcome of surveillance protocols for colorectal cancer (CRC) in Lynch syndrome, as well as in familial colorectal cancer. In 2006, evaluation of the effect of registration and colonoscopic surveillance on the mortality rate associated with colorectal cancer (CRC) showed that the policy led to a substantial decrease in the mortality rate associated with CRC. Following discovery of MMR gene defects, the first predictive model that could select families for genetic testing was published by the Leiden group. In addition, over the years the registry has produced many cancer risk studies that have helped to develop appropriate surveillance protocols. Hereditary cancer registries in general, and the Lynch syndrome registry in particular, play an important role in improving the clinical management of affected families.</p
Cognitive Impairment in Long-Term Survivors of Testicular Cancer More Than 20 Years after Treatment
SIMPLE SUMMARY: Impaired cognition can be a late effect after treatment in long-term testicular cancer survivors, negatively affecting their daily life. However, little data is available beyond 20 years post-treatment. We assessed cognitive impairment in very-long-term survivors after treatment. In this study, we enrolled testicular cancer survivors with a follow-up duration â„ 20 yearsâand age-matched healthy controls. Cognitive testing included the Auditory Verbal Learning Test, Letter Fluency Test, and Trail Making Test. We used fasting blood samples to assess the presence of hypogonadism and measured cardiovascular damage and aging parameters. We included 184 testicular cancer survivors (66 chemotherapy patients, 53 radiotherapy patients, and 65 orchiectomy only patients) and 70 healthy controls. The median follow-up was 26 years. Testicular cancer survivors performed worse on cognitive tests compared to controls. In univariate analysis, the presence of hypogonadism was associated with lower cognitive scores. Physicians and patients should be informed about timely cardiovascular risk management and testosterone supplementation therapy during follow-up to reduce the risk of cognitive impairment. ABSTRACT: Background: Impaired cognition can be a late effect after treatment in long-term testicular cancer (TC) survivors, negatively affecting their daily life. However, little data is available beyond 20 years post-treatment. We assessed cognitive impairment in very long-term TC survivors after CT or RT and compared the results with stage I TC survivors and controls. Methods: In this cross-sectional multicenter cohort study, we enrolled TC survivors (treated with orchiectomy followed by CT or RT or orchiectomy only)âwith a follow-up duration â„ 20 yearsâand age-matched healthy controls. Cognitive testing included the Auditory Verbal Learning Test, Letter Fluency Test, Category Fluency Test, and Trail Making Test. We used fasting blood samples to assess the presence of hypogonadism and measured cardiovascular aging parameters, including carotid pulse wave velocity (c-PWV) and advanced glycation end products (AGEs). Results: We included 184 TC survivors (66 CT patients, 53 RT patients, and 65 orchiectomy-only patients) and 70 healthy controls. The median follow-up was 26 years (range: 20â42). TC survivors had a lower combined score of the cognitive tests (mean cumulative Z-score â0.85; 95% CI â1.39 to â0.33) compared to controls (mean 0.67; 95% CI â0.21 to 1.57, p < 0.01). In univariate analysis, the presence of hypogonadism (ÎČ â1.50, p < 0.01), high c-PWV (ÎČ â0.35, p = 0.09), and high AGEs (ÎČ â1.27, p = 0.02) were associated with lower cognitive scores, while only AGEs (ÎČ â1.17, p = 0.03) remained a significant predictor in multivariate analysis (Model R2 0.31, p < 0.01). Conclusions: Long-term TC survivors performed worse on cognitive tests compared to controls. Physicians and patients should be informed about timely cardiovascular risk management and testosterone supplementation therapy during follow-up to reduce the risk of cognitive impairment. Trial Registration: NCT02572934
Approximation of substantive criminal law in the EU
This book dedicated to the substantive criminal law in the EU put the Libson Treaty under scrutiny. It evaluates the changes introduced by this new Treaty and their impact, before reflecting on future prospects
Prognostic Value of the Modified Rutgeerts Score for Long-Term Outcomes After Primary Ileocecal Resection in Crohnâs Disease
IntroductionThe prognostic value of the modified Rutgeerts score (mRS) in patients with Crohn's disease (CD) needs to be further elucidated. This study assessed the prognostic value of the mRS for long-term outcomes after primary ileocecal resection in patients with CD.METHODS: Patients with CD after primary ileocecal resection with an available mRS at first postoperative ileocolonoscopy (index mRS) were retrospectively included. The primary outcome was surgical recurrence. Secondary outcomes were clinical recurrence and progression to severe endoscopic recurrence (âĄi3). Cox proportional hazard models were used to assess the association between index mRS and outcomes. RESULTS: Six hundred fifty-two patients were included (mean follow-up: 6.4 years, SD: 4.6). Surgical recurrence rates were 7.7%, 5.3%, 12.9%, 19.1%, 28.8%, 47.8% for index mRS i0, i1, i2a, i2b, i3, and i4, respectively. Clinical recurrence occurred in 42.2% (i0), 53.7% (i1), 58.5% (i2a), 80.2% (i2b), 79.4% (i3), and 95.3% (i4) of patients. Progression to severe endoscopic recurrence occurred in 21.1% (i0), 33.9% (i1), 26.8% (i2a), and 33.3% (i2b) of patients. An index mRS of i2b (adjusted hazard ratio [aHR] 3.0; 1.5â5.6), i3 (aHR 4.0; 2.0â7.9) and i4 (aHR 8.0; 4.0â16.0) were associated with surgical recurrence. An index mRS of i1 (aHR 1.7; 1.2â2.4), i2a (aHR 1.7; 1.2â2.4), i2b (aHR 4.4; 3.2â6.0), i3 (aHR 3.6; 2.5â5.2), and i4 (aHR 7.3; 4.8â10.9) were associated with clinical recurrence. An index mRS of i1 (aHR 2.0; 1.1â3.7) or i2b (aHR 2.5; 1.4â4.6) was associated with progression to severe endoscopic recurrence.DISCUSSION: The increasing mRS corresponds closely with the risk of surgical and clinical recurrence. An index mRS ⥠i2b is associated with surgical recurrence, an index mRS ⥠i1 is associated with clinical recurrence, and i1 or i2b with progression to severe endoscopic recurrence. These results support tight monitoring of disease activity and treatment optimization in patients with ileal lesions and a more conservative management in patients with anastomotic lesions.</p
Prognostic Value of the Modified Rutgeerts Score for Long-Term Outcomes After Primary Ileocecal Resection in Crohnâs Disease
IntroductionThe prognostic value of the modified Rutgeerts score (mRS) in patients with Crohn's disease (CD) needs to be further elucidated. This study assessed the prognostic value of the mRS for long-term outcomes after primary ileocecal resection in patients with CD.METHODS: Patients with CD after primary ileocecal resection with an available mRS at first postoperative ileocolonoscopy (index mRS) were retrospectively included. The primary outcome was surgical recurrence. Secondary outcomes were clinical recurrence and progression to severe endoscopic recurrence (âĄi3). Cox proportional hazard models were used to assess the association between index mRS and outcomes. RESULTS: Six hundred fifty-two patients were included (mean follow-up: 6.4 years, SD: 4.6). Surgical recurrence rates were 7.7%, 5.3%, 12.9%, 19.1%, 28.8%, 47.8% for index mRS i0, i1, i2a, i2b, i3, and i4, respectively. Clinical recurrence occurred in 42.2% (i0), 53.7% (i1), 58.5% (i2a), 80.2% (i2b), 79.4% (i3), and 95.3% (i4) of patients. Progression to severe endoscopic recurrence occurred in 21.1% (i0), 33.9% (i1), 26.8% (i2a), and 33.3% (i2b) of patients. An index mRS of i2b (adjusted hazard ratio [aHR] 3.0; 1.5â5.6), i3 (aHR 4.0; 2.0â7.9) and i4 (aHR 8.0; 4.0â16.0) were associated with surgical recurrence. An index mRS of i1 (aHR 1.7; 1.2â2.4), i2a (aHR 1.7; 1.2â2.4), i2b (aHR 4.4; 3.2â6.0), i3 (aHR 3.6; 2.5â5.2), and i4 (aHR 7.3; 4.8â10.9) were associated with clinical recurrence. An index mRS of i1 (aHR 2.0; 1.1â3.7) or i2b (aHR 2.5; 1.4â4.6) was associated with progression to severe endoscopic recurrence.DISCUSSION: The increasing mRS corresponds closely with the risk of surgical and clinical recurrence. An index mRS ⥠i2b is associated with surgical recurrence, an index mRS ⥠i1 is associated with clinical recurrence, and i1 or i2b with progression to severe endoscopic recurrence. These results support tight monitoring of disease activity and treatment optimization in patients with ileal lesions and a more conservative management in patients with anastomotic lesions.</p
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