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- 저자 : Langenberg, Marlies H.G. (검색결과 4 건)
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Inflammatory bowel disease and superior mesenteric artery thromboembolism
( Steven Nicolaides ),( Abhinav Vasudevan ),( Daniel Van Langenberg ) 대한장연구학회 2020 Intestinal Research Vol.18 No.1
While patients with inflammatory bowel disease are known to be at increased risk of venous thromboembolism, the risk of ar terial thrombosis is less well recognized. Here, we describe the case of a middle-aged female with a recent diagnosis of Crohn’s disease who presented to her local emergency department with acute abdominal pain. Subsequent investigations revealed a thrombus in the superior mesenteric artery resulting in multi-organ infarction requiring major intra-abdominal surgery and extensive resection of segments of small and large bowel. (Intest Res 2020;18:130-133)
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( Danny Con ),( Bridgette Andrew ),( Steven Nicolaides ),( Daniel R Van Langenberg ),( Abhinav Vasudevan ) 대한장연구학회 2022 Intestinal Research Vol.20 No.1
Background/Aims: The residual risk of colectomy after infliximab salvage in steroid-refractory acute severe ulcerative colitis (ASUC) is required to inform the need for subsequent maintenance biologic therapy. The aim of this study was to determine the dynamic response of common serum biomarkers to infliximab salvage and assess their utility in predicting subsequent colectomy. Methods: A retrospective single-center cohort study was conducted on all patients who received infliximab salvage for steroid-refractory ASUC between January 1, 2010, and July 31, 2019. Biomarkers were assessed on admission and days 1 and 3 post infliximab, and included C-reactive protein (CRP)-albumin-ratio (CAR), CRP-lymphocyte-ratio (CLR), platelet-lym phocyte-ratio (PLR) and neutrophil-lymphocyte-ratio (NLR). Results: Of 94 patients (median age, 35 years; 67% of male), 20% required colectomy at 12 months. Biomarkers on day 3 post-infliximab best differentiated nonresponders, who had higher CRP, lower albumin and lower lymphocyte count (each P< 0.05). Day 3 predictive performance (area under the curve) for 12-month colectomy was best for CAR (0.871) and CLR (0.874), which were similar to Lindgren (0.829; P >0.05) but superior to Mayo (0.726), partial Mayo (0.719), PLR (0.719), Ho index (0.714), NLR (0.675), Travis score (0.657) and endoscopic Mayo (0.609) (each P<0.05). A day 3 CAR cutoff of 0.47 mg/g had 79% sensitivity, 80% specificity, 94% negative predictive value (NPV) to predict colectomy; while a day 3 CLR cutoff of 6.0 mg/10<sup>9</sup> had 84% sensitivity, 84% specificity, 96% NPV. Conclusions: CAR and CLR measured on day 3 post infliximab salvage for steroid-refractory ASUC represent simple and routinely performed bio markers that appear to be strong predictors of colectomy. Prospective studies are required to confirm the utility of these predic tive scores. (Intest Res 2022;20:101-113)
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The impact of tobacco smoking on treatment choice and efficacy in inflammatory bowel disease
( Steven Nicolaides ),( Abhinav Vasudevan ),( Tony Long ),( Daniel Van Langenberg ) 대한장연구학회 2021 Intestinal Research Vol.19 No.2
Smoking significantly increases the risk of developing and worsens Crohn’s disease (CD), yet protects against the development and reduces the severity of ulcerative colitis. It is less clear whether smoking impacts the efficacy of therapeutics in inflamma tory bowel disease (IBD). We review the literature regarding the relationship between smoking and the efficacy of medical and surgical therapy in IBD. Smoking is associated with alterations in thiopurine metabolism and may affect time to disease relapse. The outcomes of anti-tumor necrosis factor therapy in active smokers appear neutral with data lacking for newer biologics. Smoking increases the risk of postoperative recurrence in those requiring resection for CD, likely attributable to perturbations of the gut microbiota although further implications of these for disease onset/progression and treatment efficacy remain un clear. Multiple lifestyle and psychosocial confounders are likely under-recognized cofactors in the association between smok ing and IBD. Despite the widely promulgated risks associated with cigarette smoking in CD, more incisive data are required to further elucidate the actual relationship between smoking and disease pathways, while accounting for the several negative cofactors prevalent in smokers which cast uncertainty on the magnitude of the direct effect of smoking on disease pathophysi ology and the efficacy of therapy. (Intest Res 2021;19:158-170)
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Meulendijks, Didier,Jacob, Wolfgang,Voest, Emile E.,Mau-Sorensen, Morten,Martinez-Garcia, Maria,Taus, Alvaro,Fleitas, Tania,Cervantes, Andres,Lolkema, Martijn P.,Langenberg, Marlies H.G.,De Jonge, Maj American Association for Cancer Research 2017 Clinical Cancer research Vol.23 No.18
<P><B>Purpose:</B> This study investigated the safety, clinical activity, and target-associated biomarkers of lumretuzumab, a humanized, glycoengineered, anti-HER3 monoclonal antibody (mAb), in combination with the EGFR-blocking agents erlotinib or cetuximab in patients with advanced HER3-positive carcinomas.</P><P><B>Experimental Design:</B> The study included two parts: dose escalation and dose extension phases with lumretuzumab in combination with either cetuximab or erlotinib, respectively. In both parts, patients received lumretuzumab doses from 400 to 2,000 mg plus cetuximab or erlotinib according to standard posology, respectively. The effect of <I>HRG</I> mRNA and <I>HER3</I> mRNA and protein expression were investigated in a dedicated extension cohort of squamous non–small cell lung cancer (sqNSCLC) patients treated with lumretuzumab and erlotinib.</P><P><B>Results:</B> Altogether, 120 patients were treated. One dose-limiting toxicity (DLT) in the cetuximab part and two DLTs in the erlotinib part were reported. The most frequent adverse events were gastrointestinal and skin toxicities, which were manageable. The objective response rate (ORR) was 6.1% in the cetuximab part and 4.2% in the erlotinib part. In the sqNSCLC extension cohort of the erlotinib part, higher tumor <I>HRG</I> and <I>HER3</I> mRNA levels were associated with a numerically higher disease control rate but not ORR.</P><P><B>Conclusions:</B> The toxicity profile of lumretuzumab in combination with cetuximab and erlotinib was manageable, but only modest clinical activity was observed across tumor types. In the sqNSCLC cohort, there was no evidence of meaningful clinical benefit despite enriching for tumors with higher <I>HRG</I> mRNA expression levels. <I>Clin Cancer Res; 23(18); 5406–15. ©2017 AACR</I>.</P>
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