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Article: Defining the Failure of Medical Therapy for Inflammatory Bowel Disease in the Era of Advanced Therapies: A Systematic Review.

State, Monica / Negreanu, Lucian

2023 Volume 11, Issue 2

Abstract: Background: The expansion of advanced therapies for inflammatory bowel disease created a lag between the development of these new therapies and their incorporation and use in daily practice. At present, no clear definitions for treatment optimization, ... ...

Abstract	Background: The expansion of advanced therapies for inflammatory bowel disease created a lag between the development of these new therapies and their incorporation and use in daily practice. At present, no clear definitions for treatment optimization, treatment failure or criteria to abandon therapy are available. We aimed to centralize criteria for a nonresponse to all available molecules and to summarize guideline principles for treatment optimization. Methods: We conducted a systematic review of studies that reported criteria for the treatment response to all advanced therapies (infliximab, adalimumab, golimumab, ustekinumab, vedolizumab and tofacitinib) in patients with inflammatory bowel disease. Results: Across trials, criteria for a response of both patients with ulcerative colitis and Crohn's disease are heterogenous. Investigators use different definitions for clinical and endoscopic remission, and endoscopic response and outcomes are assessed at variable time points. Current society guidelines provide heterogenous recommendations on treatment optimization. Most available data on loss of response concern anti-TNF molecules, and newer therapies are not included in the guidelines. Conclusion: The lack of clear definitions and formal recommendations provide the premise for empirical treatment strategies and premature abandonment of therapies.
Language	English
Publishing date	2023-02-13
Publishing country	Switzerland
Document type	Journal Article ; Review
ZDB-ID	2720867-9
ISSN	2227-9059
ISSN	2227-9059
DOI	10.3390/biomedicines11020544
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Article ; Online: Quality of colonoscopy preparation in patients with inflammatory bowel disease: retrospective analysis of 348 colonoscopies.

Negreanu, Lucian / Voiosu, Theodor / State, Monica / Mateescu, Radu Bogdan

The Journal of international medical research

2020 Volume 48, Issue 4, Page(s) 300060520903654

MeSH term(s)	Adult ; Cathartics/pharmacology ; Colon/diagnostic imaging ; Colon/pathology ; Colonoscopy/standards ; Female ; Follow-Up Studies ; Humans ; Inflammatory Bowel Diseases/diagnosis ; Inflammatory Bowel Diseases/diagnostic imaging ; Male ; Retrospective Studies
Chemical Substances	Cathartics
Language	English
Publishing date	2020-04-01
Publishing country	England
Document type	Journal Article
ZDB-ID	184023-x
ISSN	1473-2300 ; 0300-0605 ; 0142-2596
ISSN (online)	1473-2300
ISSN	0300-0605 ; 0142-2596
DOI	10.1177/0300060520903654
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Zs.A 925: Show issues

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Article ; Online: Surrogate markers of mucosal healing in inflammatory bowel disease: A systematic review.

State, Monica / Negreanu, Lucian / Voiosu, Theodor / Voiosu, Andrei / Balanescu, Paul / Mateescu, Radu Bogdan

World journal of gastroenterology

2021 Volume 27, Issue 16, Page(s) 1828–1840

Abstract: Background: Mucosal healing (MH) has emerged as a key therapeutic target in inflammatory bowel disease (IBD), and achievement of this goal is documented by endoscopy with biopsy. However, colonoscopy is burdensome and invasive, and substitution with an ... ...

Abstract	Background: Mucosal healing (MH) has emerged as a key therapeutic target in inflammatory bowel disease (IBD), and achievement of this goal is documented by endoscopy with biopsy. However, colonoscopy is burdensome and invasive, and substitution with an accurate noninvasive biomarker is desirable. Aim: To summarize published data regarding the performance of noninvasive biomarkers in assessing MH in IBD patients. Methods: We conducted a systematic review of studies that reported the performance of biomarkers in diagnosing MH in patients with IBD. The main outcome measure was to review the diagnostic accuracy of serum and fecal markers that showed promising utility in assessing MH. Results: We screened 1301 articles, retrieved 46 manuscripts and included 23 articles for full-text analysis. The majority of the included manuscripts referred to fecal markers (12/23), followed by circulatory markers (8/23); only 3/23 of the included manuscripts investigated combined markers (serum and/or fecal markers). Fecal calprotectin (FC) was the most investigated fecal marker for assessing MH. In ulcerative colitis, for cutoff levels ranging between 58 mcg/g and 490 mcg/g, the sensitivity was 89.7%-100% and the specificity was 62%-93.3%. For Crohn's disease, the cutoff levels of FC ranged from 71 mcg/g to 918 mcg/g (sensitivity 50%-95.9% and specificity 52.3%-100%). The best performance for a serum marker was observed for the endoscopic healing index, which showed a comparable accuracy to the measurement of FC and a higher accuracy than the measurement of serum C-reactive protein. Conclusion: Several promising biomarkers of MH are emerging but cannot yet substitute for endoscopy with biopsy due to issues with reproducibility and standardization.
MeSH term(s)	Biomarkers ; Colitis, Ulcerative/diagnosis ; Feces ; Humans ; Inflammatory Bowel Diseases/diagnosis ; Leukocyte L1 Antigen Complex ; Reproducibility of Results ; Severity of Illness Index
Chemical Substances	Biomarkers ; Leukocyte L1 Antigen Complex
Language	English
Publishing date	2021-04-30
Publishing country	United States
Document type	Journal Article ; Systematic Review
ZDB-ID	2185929-2
ISSN	2219-2840 ; 1007-9327
ISSN (online)	2219-2840
ISSN	1007-9327
DOI	10.3748/wjg.v27.i16.1828
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Zs.A 6039: Show issues

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Article ; Online: Tissue and Circulating MicroRNA-31, MicroRNA-200b, and MicroRNA-200c Reflects Disease Activity in Crohn's Disease Patients: Results from the BIOMIR Study.

Tocia, Cristina / Dumitru, Andrei / Mateescu, Bogdan / Negreanu, Lucian / State, Monica / Cozaru, Georgeta Camelia / Mitroi, Anca Florentina / Brinzan, Costel / Popescu, Razvan / Leopa, Nicoleta / Iordache, Miorita Melina / Manea, Mihaela / Matei, Elena / Dumitru, Eugen / Alexandrescu, Luana

Journal of gastrointestinal and liver diseases : JGLD

2023 Volume 32, Issue 1, Page(s) 30–38

Abstract: Background and aims: MicroRNAs (miR) have altered expression in multiple autoimmune disorders including inflammatory bowel disease. The aim of the study was to assess the tissue and circulating miR-31, miR-200b, and miR-200c expression levels as ... ...

Abstract	Background and aims: MicroRNAs (miR) have altered expression in multiple autoimmune disorders including inflammatory bowel disease. The aim of the study was to assess the tissue and circulating miR-31, miR-200b, and miR-200c expression levels as potential biomarkers for intestinal disease activity in patients with Crohn's disease (CD). Methods: The study included 45 patients with histopathological confirmed CD and active disease (defined as fecal calprotectin >50 μg/g and Simple Endoscopic Score (SES) of CD >3), and 21 subjects as controls for the validation cohort. Demographic and clinical data, biomarkers (fecal calprotectin), endoscopy data, the expression levels of miR-31, miR-200b, and miR-200c in tissue and serum were assessed (by RT-PCR). Receiver operating characteristic analysis was performed to assess the miR-31, miR-200b, and miR-200c expression levels as potential biomarkers for active CD. Results: Mean fecal calprotectin was 1540±890 μg/g. Mean SES-CD was 8.9±4.2. Tissue and circulating miR- 31 were significantly correlated with fecal calprotectin (r=0.81, r=0.83, p<0.01) and with SES-CD (r=0.82, r=0.79, p<0.01). The expression level of miR-31 was significantly upregulated in CD tissue cases compared to the control tissue samples (6.24±1.57 vs. 3.70±1.44; p <0.01). Similarly, serum miR-31 expression levels in CD patients were significantly upregulated compared to the control serum samples (0.78±0.42 vs. -2.07±1.00; p<0.01). The expression levels of tissue miR-200b and miR-200c were significantly upregulated in CD tissue cases compared to the control tissue samples (-5.25±0.93 vs. -4.69±0.80, p=0.03 for miR-200b, and -0.86±0.96 vs. 0.39±0.66, p<0.01 for miR-200c). Similarly, serum miR-200b and miR-200c expression levels in CD patients were significantly upregulated compared to the control serum samples (p < 0.05). Receiver operating characteristic analysis revealed that the expression levels of the selected miRNAs could help to discriminate active CD patients from healthy controls with very good specificity and sensitivity. Conclusions: Tissue and circulating miR-31, miR-200b, and miR-200c reflect disease activity in CD patients and can be used as biomarkers for active disease.
MeSH term(s)	Humans ; Circulating MicroRNA/genetics ; Crohn Disease/diagnosis ; Crohn Disease/genetics ; MicroRNAs/genetics ; Biomarkers ; Leukocyte L1 Antigen Complex
Chemical Substances	Circulating MicroRNA ; MicroRNAs ; Biomarkers ; Leukocyte L1 Antigen Complex ; MIRN31 microRNA, human
Language	English
Publishing date	2023-03-31
Publishing country	Romania
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2427021-0
ISSN	1842-1121 ; 1841-8724
ISSN (online)	1842-1121
ISSN	1841-8724
DOI	10.15403/jgld-4656
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Zs.A 3825: Show issues

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Article ; Online: Squamous metaplasia within a sigmoid adenoma. A rare feature.

Tîrcol, Simona Andreea / Ghidersa, Andreea / Negreanu, Lucian / Sajin, Maria / Dumitru, Adrian Vasile

Romanian journal of morphology and embryology = Revue roumaine de morphologie et embryologie

2020 Volume 61, Issue 1, Page(s) 235–239

Abstract: Squamous metaplasia occurring within a colorectal polyp is a rare finding, having a reported incidence of approximately 0.44%. The origin of the squamous cells in this type of setting is uncertain (mechanical irritation and chronic inflammation are ... ...

Abstract	Squamous metaplasia occurring within a colorectal polyp is a rare finding, having a reported incidence of approximately 0.44%. The origin of the squamous cells in this type of setting is uncertain (mechanical irritation and chronic inflammation are potential predisposing factors). It has been implied that the significance of squamous metaplasia in colorectal adenomas is that of a preneoplastic lesion for squamous cell and adenosquamous carcinoma, however the evidence to support this statement is scarce. We present a case of a large tubulovillous adenoma located in the sigmoid, with low-grade dysplasia and multiple foci of p16-positive immunoexpression squamous metaplasia in a 54-year-old Caucasian male, presenting with rectal bleeding.
MeSH term(s)	Adenoma/pathology ; Carcinoma, Squamous Cell/pathology ; Humans ; Male ; Metaplasia/pathology ; Middle Aged ; Rare Diseases
Language	English
Publishing date	2020-07-31
Publishing country	Romania
Document type	Case Reports ; Journal Article
ZDB-ID	1062519-7
ISSN	2066-8279 ; 1220-0522 ; 0035-4007
ISSN (online)	2066-8279
ISSN	1220-0522 ; 0035-4007
DOI	10.47162/RJME.61.1.26
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Zs.A 1105: Show issues

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Article: Real-World Endoscopic and Histologic Outcomes in Ulcerative Colitis Patients: A Retrospective Cohort Study.

State, Monica / Balanescu, Paul / Voiosu, Theodor / Bengus, Andreea / Voiosu, Andrei / Coman, Andrei / Mustatea, Petronel / Negreanu, Lucian / Mateescu, Radu Bogdan / Popp, Cristiana

Biomedicines

2023 Volume 11, Issue 7

Abstract: Background: Histologic activity has emerged as an aspirational therapeutic goal in ulcerative colitis management. It is not yet a formal treatment target in ulcerative colitis. However, it could be used as an adjunct to mucosal healing to represent a ... ...

Abstract	Background: Histologic activity has emerged as an aspirational therapeutic goal in ulcerative colitis management. It is not yet a formal treatment target in ulcerative colitis. However, it could be used as an adjunct to mucosal healing to represent a deeper level of healing. We investigated mucosal and histologic remission rates and potential predictors of these outcomes in a cohort of UC patients. Methods: We conducted a retrospective analysis of data collected from UC patients enrolled in an ongoing prospective cohort study. Mucosal healing was defined as Mayo endoscopic score = 0. Results: A total of 131 patients with ulcerative colitis were enrolled in our study and were prospectively followed for a median length of 2 years (range 0-5 years), totaling 266 study visits. Mucosal healing was recorded for 27 patients at 70 (26%) different study visits. For patients with mucosal healing, histologic remission was achieved in 18/27 (66%) patients. On univariate analysis, sustained clinical remission, SIBDQ scores ≥ 5.5, CRP ≤ 5 mg/dL and absence of corticotherapy were associated with mucosal healing and SIBDQ scores ≥ 5.5 and CRP ≤ 5 mg/dL with histologic healing, respectively. After logistic regression analysis, none of the investigated factors were associated with mucosal and histologic healing. The number of CD8+ intraepithelial lymphocytes (IELs) was significantly greater than the number of CD4+ IELs in periods of disease activity, as well as during mucosal healing ( Conclusions: Mucosal healing and histologic remission rates are low in real-life settings. The results of univariate analysis indicate that a good quality of life (SIBDQ score) and normal inflammatory markers (CRP) are associated with mucosal and histologic healing. However, frequently used patient- and disease-related factors, including mucosal healing, are not reliable predictors for histologic remission. Greater CD8+ lymphocyte involvement and higher CD8+/CD4+ distribution can have a meaningful impact on understanding the pathogenesis and natural history of ulcerative colitis, as well as future treatment options for lymphocyte-targeting medications.
Language	English
Publishing date	2023-06-29
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2720867-9
ISSN	2227-9059
ISSN	2227-9059
DOI	10.3390/biomedicines11071860
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Article: Duodenal Gangliocytic Paragangliomas-Case Series and Literature Review.

Stan-Ilie, Madalina / Şandru, Vasile / Plotogea, Oana-Mihaela / Rînja, Ecaterina / Pavel, Christopher / Constantinescu, Gabriel / Negreanu, Lucian / Paduraru, Dan Nicolae / Bolocan, Alexandra / Andronic, Octavian / Davitoiu, Dragos / Bălan, Gheorghe G / Constantinescu, Alexandru

Life (Basel, Switzerland)

2023 Volume 13, Issue 3

Abstract: Duodenal gangliocytic paragangliomas are rare neuroendocrine tumors primarily localized in the periampullary area. Though mostly asymptomatic, they can present with various symptoms, most often jaundice, anemia and abdominal pain. The present paper is a ... ...

Abstract	Duodenal gangliocytic paragangliomas are rare neuroendocrine tumors primarily localized in the periampullary area. Though mostly asymptomatic, they can present with various symptoms, most often jaundice, anemia and abdominal pain. The present paper is a case series report, describing our personal experience with patients presenting to the Emergency Unit with different symptoms due to duodenal gangliocytic paraganglioma. Endoscopic resection is safe and indicated in most of the cases, being also associated with lower medical costs. EUS plays a central role in the pre-resection management and in surveillance, and immunostaining is decisive to ascertain the tumor histologic origin. In addition to reporting our experience, we researched the literature regarding these rare tumors and performed a comprehensive review.
Language	English
Publishing date	2023-02-21
Publishing country	Switzerland
Document type	Case Reports
ZDB-ID	2662250-6
ISSN	2075-1729
ISSN	2075-1729
DOI	10.3390/life13030597
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Article ; Online: Monitoring established Crohn's disease with pan-intestinal video capsule endoscopy in Europe: clinician consultation using the nominal group technique.

Carretero, Cristina / Carbonnel, Franck / Ferrante, Marc / Knudsen, Torben / Van Lent, Nancy / Lobo, Alan J / Negreanu, Lucian / Vojvodic, Ana / Oliva, Salvatore

Current medical research and opinion

2021 Volume 37, Issue 9, Page(s) 1547–1554

Abstract: Objective: Monitoring established Crohn's disease (CD) through a "treat-to-target" strategy aims to reduce and prevent long-term bowel damage and disability. Despite the availability of different monitoring techniques, there is a current lack of ... ...

Abstract	Objective: Monitoring established Crohn's disease (CD) through a "treat-to-target" strategy aims to reduce and prevent long-term bowel damage and disability. Despite the availability of different monitoring techniques, there is a current lack of integrated evidence to guide optimal monitoring in terms of appropriate tools and timing. Pan-intestinal video capsule endoscopy (PCE) enables non-invasive and direct visualization of the entire intestinal tract with proven safety and efficacy. This study aims to generate insights on the value of PCE for monitoring established CD from the physician's perspective. Methods: The Nominal Group Technique (NGT) was used to create discussion around pre-defined research questions aimed at identifying target patient populations for PCE, benefits of PCE in terms of improving disease management, comparative benefits of PCE over standard of care, research priorities to ratify the use of PCE, and hurdles to PCE utilization. A NGT panel was held in Brussels, Belgium in October 2018 with 9 gastroenterology experts. Data were collected from multiple rankings of statements to the research questions and analyzed descriptively. Results: Consensus indicated that PCE is differentiated from other diagnostic tools, allowing for non-invasive and direct visualization of the luminal intestinal tract in one single procedure. Participants agreed that PCE is beneficial for mapping and grading established CD in all patients, enabling individual and tailored treatment decision-making. Time required to read PCE results was identified as the main utilization hurdle by participants. Well-designed studies are needed to confirm improved outcomes amongst patients with CD managed through a PCE-guided approach. Conclusions: This study, using the NGT, generated expert opinion on the value of PCE for monitoring established CD in terms of target patient populations and benefits compared to other diagnostic modalities. Participants perceived PCE to facilitate a "treat-to-target" strategy for CD management. Further research is needed to support this value perception.
MeSH term(s)	Capsule Endoscopy ; Crohn Disease/diagnosis ; Europe ; Humans ; Intestines ; Referral and Consultation
Language	English
Publishing date	2021-06-30
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	80296-7
ISSN	1473-4877 ; 0300-7995
ISSN (online)	1473-4877
ISSN	0300-7995
DOI	10.1080/03007995.2021.1940910
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Zs.A 955: Show issues

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Article ; Online: Tuberculin skin test and Quantiferon TB Gold in Romanian BCG vaccinated, immunosuppressed patients with moderate-to-severe Crohn's disease: a comparison with a Hungarian cohort.

Preda, Carmen M / Fulger, Larisa E / Gheorghe, Cristian / Gheorghe, Liana / Manuc, Mircea / Negreanu, Lucian / Meianu, Corina / Slavulete, Bogdan I / Diculescu, Mircea M

Journal of gastrointestinal and liver diseases : JGLD

2016 Volume 25, Issue 2, Page(s) 260–261

MeSH term(s)	BCG Vaccine ; Crohn Disease ; Gold ; Humans ; Hungary ; Latent Tuberculosis ; Mycobacterium bovis ; Romania ; Tuberculin Test ; Tuberculosis/prevention & control
Chemical Substances	BCG Vaccine ; Gold (7440-57-5)
Language	English
Publishing date	2016-06
Publishing country	Romania
Document type	Letter ; Comment
ZDB-ID	2427021-0
ISSN	1842-1121 ; 1841-8724
ISSN (online)	1842-1121
ISSN	1841-8724
DOI	10.15403/jgld.2014.1121.252.tbg
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Article: Endoscopy in inflammatory bowel disease: from guidelines to real life.

Negreanu, Lucian / Voiosu, Theodor / State, Monica / Voiosu, Andrei / Bengus, Andreea / Mateescu, Bogdan Radu

Therapeutic advances in gastroenterology

2019 Volume 12, Page(s) 1756284819865153

Abstract: Endoscopy has a central role in the management of inflammatory bowel disease (IBD), providing crucial data for diagnostic and therapeutic decisions, treating disease-related complications, and assisting in the early detection of dysplasia and prevention ... ...

Abstract	Endoscopy has a central role in the management of inflammatory bowel disease (IBD), providing crucial data for diagnostic and therapeutic decisions, treating disease-related complications, and assisting in the early detection of dysplasia and prevention of colorectal cancer in the setting of IBD. Treatment targets have significantly shifted in IBD, focusing on achieving mucosal healing, a more meaningful endpoint than clinical remission. With the emergence of novel therapies, we aim to alter the course of the disease and prevent irreversible damage to the bowel. To that end, obtaining reliable and reproducible assessments of endoscopic disease activity has become an issue of great importance. Although several guidelines include recommendations regarding endoscopic surveillance in patients with long-standing IBD, there is an open debate regarding the best examination method and the appropriate follow-up intervals. Another important issue is whether surveillance guidelines are actually implemented in real-life practice and what is the preferred surveillance method among endoscopists. Significant changes have occurred in the endoscopic world with the development of new diagnostic and therapeutic modalities and their incorporation in everyday practice. We aimed to assess the real-life application of guideline recommendations regarding endoscopy in IBD patients and to review newly emerged data which might impact these recommendations in the near future.
Language	English
Publishing date	2019-07-24
Publishing country	England
Document type	Journal Article ; Review
ZDB-ID	2440710-0
ISSN	1756-2848 ; 1756-283X
ISSN (online)	1756-2848
ISSN	1756-283X
DOI	10.1177/1756284819865153
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