Publications of Edouard Louis
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See detailLocal Mesenchymal Stem Cells injection in Crohn’s disease strictures: a phase I-II, open-label clinical study
VIEUJEAN, Sophie ULiege; LOLY, Jean-Philippe ULiege; BOUTAFFALA, Layla ULiege et al

Poster (2021, October)

Intestinal fibrosis is a common complication of Crohn's disease (CD) leading to progressive bowel stricture formation. Mesenchymal stem cells (MSCs), known for their immunomodulatory, anti-inflammatory ... [more ▼]

Intestinal fibrosis is a common complication of Crohn's disease (CD) leading to progressive bowel stricture formation. Mesenchymal stem cells (MSCs), known for their immunomodulatory, anti-inflammatory and anti-fibrotic properties, could be a potential therapy in this frequently fibro-inflammatory condition. In this phase I–II open-label pilot trial, we aimed to assess safety and efficacy of local MSCs injection in CD strictures. CD patients with a short (less than 5 cm in lengh) non-passable stricture, accessible by ileocolonoscopy, but without intestinal obstruction, fistulas, or abscess, were included. A total of 3X107 allogenic bone-marrow derived MSCs were equally injected in the 4 quadrants of the strictured bowel wall during an ileocolonoscopy. Adverse events and clinical scores (Crohn Disease Activity Index, Short Health Scale and Crohn Disease Obstructive Score) were evaluated at each follow-up visit (at week (W) 4, 12, 24 and 48) while endoscopy and magnetic resonance enterography (MRE) were performed at baseline, W12 and W48. The main judgement criteria for efficacy was the complete (defined by the ability to pass the ileocolonoscope) or partial (defined by a diameter increase) resolution of the stricture at 12 weeks. Second efficacy criteria included complete or partial resolution of the stricture at 48 weeks as well as the evolution of clinical scores at W12 and W48. Between 2018 and 2020, we performed 11 local MSCs injections in 10 CD patients (6 females; aged to 38-65 years; median 45 years old; 70% were smoker). The strictures’ (3 primary, 7 anastomotic; 1 stricture injected twice) location was as follows: 7 at an ileo-colonic or ileo-rectal anastomosis, 1 colonic and 2 of the ileocecal valve. No patient developed abscess or fistula in the follow-up. One patient had actually a small intestinal fistula at baseline (not diagnosed by the routine imaging report but disclosed by the central reading) which remained stable. A total of 5 hospitalizations for occlusion were reported (2 secondary to a different stricture than the injected one) leading to a surgical resection for one patient and an endoscopic dilatation for another one. At 12 weeks, 5 patients (45%) presented a stricture improvement with a complete resolution for 2 and a partial resolution for 3. Of the 11 MSCs injections, 6 strictures were re-evaluated at week 48 (2 patients still undergoing follow-up, 1 operated, 1 dilated, and 1 lost to follow-up), 4 patients had a complete resolution. The evolution of clinical scores between weeks 0, 12 and 48 was not statistically significant and MSCs injection did not significantly modify the stricture characteristics analysed by MRE, except the disappearance of T2 submucosal oedema in two endoscopic responders. Local MSCs injection in non-passable CD stricture was well tolerated over the short term although several occlusions occured in the follow-up indicating insufficient therapeutic effect in thoses cases. Combining the effects of MSCs with the proven effect of endoscopic balloon dilatation could possibly improve the outcome of CD stricture. [less ▲]

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See detailMesenchymal Stem Cell Injection in Crohn's Disease Strictures: a phase I-II clinical study
VIEUJEAN, Sophie ULiege; LOLY, Jean-Philippe ULiege; BOUTAFFALA, Layla ULiege et al

in Journal of Crohn's and Colitis (2021)

Background and aim: Mesenchymal stem cells (MSCs) have anti-inflammatory and anti-fibrotic properties and could be a potential therapy for Crohn's Disease (CD) strictures. In this phase I-II pilot trial ... [more ▼]

Background and aim: Mesenchymal stem cells (MSCs) have anti-inflammatory and anti-fibrotic properties and could be a potential therapy for Crohn's Disease (CD) strictures. In this phase I-II pilot trial, we assessed safety and efficacy of local MSC injection to treat CD strictures. Methods: CD patients with a short (less than 5 cm in length) non-passable stricture accessible by ileocolonoscopy were included. Allogenic bone-marrow derived MSCs were injected in the 4 quadrants of the stricture. Adverse events and clinical scores were evaluated at each followup visit while endoscopy and magnetic resonance enterography were performed at baseline, week (W)12 and W48. The main judgement criterion for efficacy was the complete (defined by the ability to pass the ileocolonoscope) or partial (defined by a diameter increase) resolution of the stricture at W12. Second efficacy criteria included assessment of the stricture at W48 and evolution of clinical scores at W12 and W48. Results: We performed 11 MSC injections in 10 CD patients (3 primary and 7 anastomotic strictures; 1 stricture injected twice). MSC injections were well tolerated but 4 hospitalizations for occlusion were reported. At W12, 5 patients presented a complete or partial resolution of the stricture (2 complete and 3 partial). Seven patients were re-evaluated at W48 (1 dilated, 1 operated, and 1 lost to follow-up) and 4 patients had a complete resolution. The evolution of clinical scores between W0, W12 and W48 was not statistically significant. Conclusion: MSCs injection in CD stricture was well tolerated and may offer a benefit. [less ▲]

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See detailUnusual intra-rectal “laterally spreading tumour” in immunosuppressed patient with ulcerative colitis
VIEUJEAN, Sophie ULiege; LATOUR, Pascale ULiege; COIMBRA MARQUES, Carla ULiege et al

in Acta Gastro-Enterologica Belgica (2021)

Condyloma acuminatum (CA) is a manifestation of Human Papillomavirus (HPV) infection which usually occurs in genital and perianal regions. We report a 46-year-old man with an ulcerative proctitis ... [more ▼]

Condyloma acuminatum (CA) is a manifestation of Human Papillomavirus (HPV) infection which usually occurs in genital and perianal regions. We report a 46-year-old man with an ulcerative proctitis diagnosed four years earlier, asymptomatic for a long time under azathioprine but without any follow-up for three years. A colonoscopy was performed prior to potential immunosuppressive treatment discontinuation and showed a circumferential “laterally spreading tumour” in the rectum. Surprisingly biopsies revealed a CA with a very focally high-grade intra-epithelial lesion. Azathioprine was stopped and a transanal surgical resection was performed. At guided anamnesis, patient confirmed to be a former active “men who have sex with men”. No recurrence of proctitis occurred despite azathioprine discontinuation. A retrospective review of the histological sections suggests that it was, in fact, an intestinal spirochetosis misdiagnosed as inflammatory bowel disease. Involvement of the rectal mucosa by HPV is a rare condition and this may have been promoted by inappropriate immunosuppressive treatment. [less ▲]

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See detailCholangite obstructive chez un patient atteint d’une hydatidose.
Basbous, C; Hayette, Marie-Pierre ULiege; LEONARD, Philippe ULiege et al

in Revue medicale de Liege (2021), 76(7-8), 575-578

The authors report the case of a 41-year-old patient originating from Algeria who developed obstructive cholangitis caused by the membrane of a ruptured hydatid cyst leading to the diagnosis of cystic ... [more ▼]

The authors report the case of a 41-year-old patient originating from Algeria who developed obstructive cholangitis caused by the membrane of a ruptured hydatid cyst leading to the diagnosis of cystic echinococcosis. Cystic echinococcosis can be asymptomatic for several years until a complication occurs, such as in this case an obstruction of the common bile duct, or cholangio-hydatidosis. This cause of jaundice is uncommon in Western Europe whereas it is more frequent in endemic areas. Identification and treatment of ruptured cysts are mandatory because of the mortality rate of these complications if left untreated. In this particular case, the treatment by endoscopic retrograde cholangiopancreatography was successful. [less ▲]

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See detailLocal Mesenchymal Stem Cells injection in Crohn’s disease strictures: a phase I-II, open-label clinical study
VIEUJEAN, Sophie ULiege; LOLY, Jean-Philippe ULiege; BOUTAFFALA, Layla ULiege et al

Poster (2021, July)

Background and aim: Intestinal fibrosis is a common complication of Crohn's disease (CD) leading to progressive bowel stricture formation. Mesenchymal stem cells (MSCs), known for their immunomodulatory ... [more ▼]

Background and aim: Intestinal fibrosis is a common complication of Crohn's disease (CD) leading to progressive bowel stricture formation. Mesenchymal stem cells (MSCs), known for their immunomodulatory, anti-inflammatory and anti-fibrotic properties, could be a potential therapy in this frequently fibro-inflammatory condition. In this phase I–II open-label pilot trial, we aimed to assess safety and efficacy of local MSCs injection in CD strictures. Methods: CD patients with a non-passable stricture, length from 2 to 5 cm, accessible by ileocolonoscopy, but without intestinal obstruction, fistulas, or abscess, could be included. A total of 3X107 allogenic bone-marrow derived MSCs were equally injected in the 4 quadrants of the strictured bowel wall during an ileocolonoscopy. Adverse events and clinical scores (Crohn Disease Activity Index, Short Health Scale and Crohn Disease Obstructive Score) were evaluated at each follow-up visit (at week 4, 12, 24 and 48) while endoscopy was performed at baseline, W12 and W48. The main judgement criteria for efficacy was the complete (defined by the ability to pass the ileocolonoscope) or partial (defined by a diameter increase) resolution of the stricture at 12 weeks. Other efficacy criteria included complete or partial resolution of the stricture at 48 weeks as well as the evolution of clinical scores between weeks 0, 12 and 48. Results: Between 2018 and 2020, we performed 11 local MSCs injections in 10 CD patients (6 female; aged to 38-65 years; median 45 years old; 70% were smoker). The strictures’ (3 primary, 7 anastomotic) location was as follows: 7 at an ileo-colonic or ileo-rectal anastomosis, 1 colonic and 2 of the ileocecal valve. MSCs injections were well tolerated but a total of 5 hospitalizations for occlusion were reported (2 secondary to a different stricture than the injected one) leading to a surgical resection for one patient and an endoscopic dilatation for another one. Neither intestinal perforation nor intra-abdominal fistula or abscess was reported. At 12 weeks, 5 patients (45%) presented a stricture improvement with a complete resolution for 2 and a partial resolution for 3. Of the 11 MSCs injections, 6 strictures were re-evaluated at week 48 (2 patients still undergoing follow-up, 1 operated, 1 dilated, and 1 lost to follow-up), 4 patients had a complete resolution and 1 had a partial resolution. The evolution of clinical scores between weeks 0, 12 and 48 (Figure 1) was not statistically significant. Conclusion: Local MSCs injection in non-passable CD stricture was well tolerated over the short term but several occlusions were reported in the follow-up. Combining the effects of MSCs with the proven effect of endoscopic balloon dilatation could possibly improve the outcome of CD stricture. [less ▲]

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See detailPotential Role of Epithelial Protein Disulphide Isomerases in Crohn’s Disease Fibrosis
VIEUJEAN, Sophie ULiege; Hu, Shurong; Bequet, Emeline ULiege et al

Poster (2021, July)

Background and aims: Intestinal fibrosis is a common complication of Crohn’s disease (CD) characterized by an accumulation of fibroblasts differentiating into activated myofibroblasts secreting excessive ... [more ▼]

Background and aims: Intestinal fibrosis is a common complication of Crohn’s disease (CD) characterized by an accumulation of fibroblasts differentiating into activated myofibroblasts secreting excessive extracellular matrix. In in-vitro experiments, this myofibroblastic differentiation is elicited by a whole series of factors among which transforming growth factor β1 (TGF-β1) seems to play a key role. The potential role of the intestinal epithelium in this fibrotic process remains poorly defined. Methods: We performed a pilot proteomic study comparing the proteome of surface epithelium isolated by laser-capture microdissection in normal and fibrotic zones of resected ileal CD strictures (13 zones collected in 5 patients). The pro-fibrotic role of selected epithelial proteins was investigated through in-vitro experiments using HT-29 epithelial cells and a CCD-18Co fibroblast to myofibroblast differentiation model. Results: Proteomic study revealed an endoplasmic reticulum (ER) stress proteins increase in the epithelium of CD ileal fibrotic strictures, including Anterior gradient protein 2 homolog (AGR2), Protein disulphide isomerase A6 (PDIA6) and Endoplasmic reticulum resident protein 44 (ERP44) which are 3 protein disulphide isomerases. In HT-29 cells, tunicamycin-induced ER stress triggered AGR2, PDIA6, ERP44 as well as TGF β1 intracellular expression and their secretion. Supernatant of these HT-29 cells, pre-conditioned by tunicamycin (Tm), led to a myofibroblastic differentiation when applied on CCD-18Co fibroblasts. The application of blocking agents for AGR2, PDIA6, ERP44 or TGF β1 in the supernatant of these Tm pre conditioned HT-29 cells, attenuated the myofibroblastic differentiation induced by this supernatant, suggesting a pro-fibrotic role of these secreted epithelial proteins. Conclusions: The development of CD fibrotic strictures may involve ER stress in epithelial cells, releasing a whole set of proteins into their environment, including AGR2, PDIA6, ERP44 as well as TGF-β1, which could exercise a pro-fibrotic role through a paracrine action. [less ▲]

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See detailIdentification of novel loci associated with human microbiota composition
Latour, Samuel ULiege; Shagam, Lev ULiege; Mariman, Rob ULiege et al

Poster (2021, June)

Our understanding of the factors shaping intestinal microbiome composition has increased significantly during last decade. Host genetics is one of these factors and may explain ~10% of the microbiome ... [more ▼]

Our understanding of the factors shaping intestinal microbiome composition has increased significantly during last decade. Host genetics is one of these factors and may explain ~10% of the microbiome variance . So far, and despite the number of GWAS studies performed to identify loci associated with microbiome composition, only few associations were cross‑replicated. This study makes use of an extensive dataset integrating 300 healthy individuals (CEDAR-1 cohort) from whom we obtained (i) genotype (Illumina Human OmniExpress BeadChip imputed to 6M SNPs with MAF⩾5%) (ii) 16S rRNA based taxonomic assignation for biopsies from the ileum, transverse colon and rectum (3 amplicons mapped to SILVA database). We performed a GWAS (PLINK additive model) to unravel new associations between genotype and microbiota. Our findings were further verified in two confirmation cohorts obtained from residual stool samples collected during colonoscopy (n=295), from ileum, transverse colon and rectum biopsies and stools (CEDAR-2 cohort) (n~ 50 and 20) where we also tested for individual variation regarding sample provenance. We observed that intestinal location explained a small part of the microbiome variability (<1%) in our dataset. The variation in microbial composition explained by the individual effect represents the major fraction (>50%). We identified three association between SNP and bacterium abundance at the experiment-wide p-value threshold (6x10-10). Among these three associations, the second and third were reproduced at nominal p value of 5% in the confirmation cohort. We have identified 2 putative novel loci associated with human microbiome composition . We also showed a strong individual effect on bacterial communities and a low location variability across the intestinal tract. [less ▲]

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See detailPotential Role of Epithelial Endoplasmic Reticulum Stress and Anterior Gradient Protein 2 Homolog in Crohn’s Disease Fibrosis
VIEUJEAN, Sophie ULiege; Hu, Shurong; Bequet, Emeline ULiege et al

in Journal of Crohn's and Colitis (2021)

Background and aims: Intestinal fibrosis is a common complication of Crohn’s disease (CD). It is characterised by an accumulation of fibroblasts differentiating into myofibroblasts secreting excessive ... [more ▼]

Background and aims: Intestinal fibrosis is a common complication of Crohn’s disease (CD). It is characterised by an accumulation of fibroblasts differentiating into myofibroblasts secreting excessive extracellular matrix. The potential role of the intestinal epithelium in this fibrotic process remains poorly defined. Methods: We performed a pilot proteomic study comparing the proteome of surface epithelium, isolated by laser-capture microdissection, in normal and fibrotic zones of resected ileal CD strictures (13 zones collected in 5 patients). Proteins of interests were validated by immunohistochemistry (IHC) in ileal and colonic samples of stricturing CD (n=44), pure inflammatory CD (n=29) and control (n=40) subjects. The pro-fibrotic role of one selected epithelial protein was investigated through in-vitro experiments using HT-29 epithelial cells and a CCD-18Co fibroblast to myofibroblast differentiation model. Results: Proteomic study revealed an endoplasmic reticulum (ER) stress proteins increase in the epithelium of CD ileal fibrotic strictures, including Anterior gradient protein 2 homolog (AGR2) and Binding-immunoglobulin protein (BiP). This was confirmed by IHC. In HT-29 cells, tunicamycin-induced ER stress triggered AGR2 intracellular expression and its secretion. Supernatant of these HT-29 cells, pre-conditioned by tunicamycin, led to a myofibroblastic differentiation when applied on CCD-18Co fibroblasts. By using recombinant protein and blocking agent for AGR2, we demonstrated that the secretion of this protein by epithelial cells can play a role in the myofibroblastic differentiation. Conclusions: The development of CD fibrotic strictures could involve epithelial ER stress and particularly the secretion of AGR2. [less ▲]

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See detailPotential Role of Epithelial Protein Disulphide Isomerases in Crohn’s Disease Fibrosis
Vieujean, Sophie ULiege; Hu, Shurong; Bequet, Emeline ULiege et al

in Acta Gastro-Enterologica Belgica (2021, March 03)

Background and aims: Intestinal fibrosis is a common complication of Crohn’s disease (CD) characterized by an accumulation of fibroblasts differentiating into activated myofibroblasts secreting excessive ... [more ▼]

Background and aims: Intestinal fibrosis is a common complication of Crohn’s disease (CD) characterized by an accumulation of fibroblasts differentiating into activated myofibroblasts secreting excessive extracellular matrix. In in-vitro experiments, this myofibroblastic differentiation is elicited by a whole series of factors among which transforming growth factor β1 (TGF-β1) seems to play a key role. The potential role of the intestinal epithelium in this fibrotic process remains poorly defined. Methods: We performed a pilot proteomic study comparing the proteome of surface epithelium isolated by laser-capture microdissection in normal and fibrotic zones of resected ileal CD strictures (13 zones collected in 5 patients). The pro-fibrotic role of selected epithelial proteins was investigated through in-vitro experiments using HT-29 epithelial cells and a CCD-18Co fibroblast to myofibroblast differentiation model. Results: Proteomic study revealed an endoplasmic reticulum (ER) stress proteins increase in the epithelium of CD ileal fibrotic strictures, including Anterior gradient protein 2 homolog (AGR2), Protein disulphide isomerase A6 (PDIA6) and Endoplasmic reticulum resident protein 44 (ERP44) which are 3 protein disulphide isomerases. In HT-29 cells, tunicamycin-induced ER stress triggered AGR2, PDIA6, ERP44 as well as TGF β1 intracellular expression and their secretion. Supernatant of these HT-29 cells, pre-conditioned by tunicamycin (Tm), led to a myofibroblastic differentiation when applied on CCD-18Co fibroblasts. The application of blocking agents for AGR2, PDIA6, ERP44 or TGF β1 in the supernatant of these Tm pre conditioned HT-29 cells, attenuated the myofibroblastic differentiation induced by this supernatant, suggesting a pro-fibrotic role of these secreted epithelial proteins. Conclusions: The development of CD fibrotic strictures may involve ER stress in epithelial cells, releasing a whole set of proteins into their environment, including AGR2, PDIA6, ERP44 as well as TGF-β1, which could exercise a pro-fibrotic role through a paracrine action. [less ▲]

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See detailSolute carrier family 12 member 2 as a proteomic and histological biomarker of dysplasia and neoplasia in ulcerative colitis.
Merli, Angela-Maria ULiege; Vieujean, Sophie ULiege; MASSOT, Charlotte ULiege et al

in Journal of Crohn's & colitis (2021), 15(2), 287-297

BACKGROUND AND AIMS: Ulcerative colitis (UC) patients have a greater risk of developing colorectal cancer through inflammation-dysplasia-carcinoma sequence of transformation. The histopathological ... [more ▼]

BACKGROUND AND AIMS: Ulcerative colitis (UC) patients have a greater risk of developing colorectal cancer through inflammation-dysplasia-carcinoma sequence of transformation. The histopathological diagnosis of dysplasia is therefore of critical clinical relevance, but dysplasia may be difficult to distinguish from inflammatory changes. METHODS: A proteomic pilot study on 5 UC colorectal dysplastic patients highlighted proteins differentially distributed between paired dysplastic, inflammatory and normal tissues. The best candidate marker was selected and immunohistochemistry confirmation was performed on AOM/DSS mouse model lesions, 37 UC dysplasia, 14 UC cancers, 23 longstanding UC, 35 sporadic conventional adenomas, 57 sporadic serrated lesions and 82 sporadic colorectal cancers. RESULTS: Differential proteomics found 11 proteins significantly more abundant in dysplasia compared to inflammation, including Solute carrier family 12 member 2 (SLC12A2) which was confidently identified with 8 specific peptides and was below the limit of quantitation in both inflammatory and normal colon. SLC12A2 immunohistochemical analysis confirmed the discrimination of preneoplastic and neoplastic lesions from inflammatory lesions in mice, UC and in sporadic contexts. A specific SLC12A2 staining pattern termed "loss of gradient" reached 89% sensitivity, 95% specificity and 92% accuracy for UC-dysplasia diagnosis together with an inter-observer agreement of 95.24% (multirater κfree of 0.90; IC95%: 0.78 - 1.00). Such discrimination could not be obtained by Ki67 staining. This specific pattern was also associated with sporadic colorectal adenomas and cancers. CONCLUSIONS: We found a specific SLC12A2 immunohistochemical staining pattern in precancerous and cancerous colonic UC-lesions which could be helpful for diagnosing dysplasia and cancer in UC and non-UC patients. [less ▲]

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See detailEditorial: Personalizing Treatment in IBD: Hype or Reality in 2020?
Gomollón, Fernando; Louis, Edouard ULiege

in Frontiers in Medicine (2021), 8

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See detailStratégie «Watch and Wait» dans la prise en charge des adénocarcinomes du rectum.
LABILLE, Virginie ULiege; Louis, Edouard ULiege; LOLY, Catherine ULiege

in Revue medicale de Liege (2021), 76(5-6), 515-518

Currently, the standard management of locally advanced adenocarcinoma of the middle and lower rectum consists in first intention of pre-operative radio-chemotherapy. This treatment is then usually ... [more ▼]

Currently, the standard management of locally advanced adenocarcinoma of the middle and lower rectum consists in first intention of pre-operative radio-chemotherapy. This treatment is then usually followed by rectal surgery with removal of the mesorectum. The local recurrence rate is quite low, but at the cost of a non negligible morbidity (urinary, anal and sexual functional sequelae). This raises the question of a possible sparing of surgery and therefore organ preservation in well selected patients with a complete response after radio-chemotherapy. The Brazilians are pioneers in this field. Already in 2004, their publications suggested that the «Watch and Wait» strategy was safe and effective in patients with a complete clinical response. Other publications have followed and tend to confirm that there is no oncological risk in proposing a «watch and wait» strategy for these well selected patients in complete clinical, endoscopic and iconographic remission on the basis of magnetic resonance imaging (MRI). In these conditions, an attentive surveillance strategy allows to avoid operative morbi-mortality without oncological compromise. Monitoring is therefore multi-modal, clinical and endoscopic, but also based on MRI. [less ▲]

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See detailTofacitinib De-escalation Strategy in Ulcerative Colitis: Is It the End of the Story?
Guillo, Lucas; Peyrin-Biroulet, Laurent; Louis, Edouard ULiege

in Journal of Crohn's & colitis (2021), 15(7), 1087-1088

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See detailA Blood Exosomal miRNA Signature in Acute Respiratory Distress Syndrome.
Parzibut, Gilles ULiege; Henket, Monique ULiege; Moermans, Catherine ULiege et al

in Frontiers in Molecular Biosciences (2021), 8

Acute respiratory distress syndrome (ARDS) is a diffuse, acute, inflammatory lung disease characterized by a severe respiratory failure. Recognizing and promptly treating ARDS is critical to combat the ... [more ▼]

Acute respiratory distress syndrome (ARDS) is a diffuse, acute, inflammatory lung disease characterized by a severe respiratory failure. Recognizing and promptly treating ARDS is critical to combat the high mortality associated with the disease. Despite a significant progress in the treatment of ARDS, our ability to identify early patients and predict outcomes remains limited. The development of novel biomarkers is crucial. In this study, we profiled microRNA (miRNA) expression of plasma-derived exosomes in ARDS disease by small RNA sequencing. Sequencing of 8 ARDS patients and 10 healthy subjects (HSs) allowed to identify 12 differentially expressed exosomal miRNAs (adjusted p < 0.05). Pathway analysis of their predicted targets revealed enrichment in several biological processes in agreement with ARDS pathophysiology, such as inflammation, immune cell activation, and fibrosis. By quantitative RT-PCR, we validated the alteration of nine exosomal miRNAs in an independent cohort of 15 ARDS patients and 20 HSs, among which seven present high capability in discriminating ARDS patients from HSs (area under the curve > 0.8) (miR-130a-3p, miR-221-3p, miR-24-3p, miR-98-3p, Let-7d-3p, miR-1273a, and miR-193a-5p). These findings highlight exosomal miRNA dysregulation in the plasma of ARDS patients which provide promising diagnostic biomarkers and open new perspectives for the development of therapeutics. [less ▲]

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See detailQuality of Life and Work Productivity Improvements with Upadacitinib: Phase 2b Evidence from Patients with Moderate to Severe Crohn’s Disease
Peyrin-Biroulet, L.; Louis, Edouard ULiege; Loftus, E. V. et al

in Advances in Therapy (2021)

Introduction: In the phase 2 CELEST study, positive efficacy results were obtained with the Janus kinase 1 inhibitor upadacitinib for adult patients with moderate to severe Crohn’s disease. We present the ... [more ▼]

Introduction: In the phase 2 CELEST study, positive efficacy results were obtained with the Janus kinase 1 inhibitor upadacitinib for adult patients with moderate to severe Crohn’s disease. We present the health-related quality of life and work productivity improvement results with upadacitinib from CELEST. Methods: CELEST (NCT02365649) was a double-blind study where patients were randomized 1:1:1:1:1:1 in the 16-week induction period to placebo or upadacitinib 3 mg twice daily (BID), 6 mg BID, 12 mg BID, 24 mg BID, or 24 mg once daily (QD). Patients completing the induction period were re-randomized 1:1:1 to receive upadacitinib 3 mg BID, 12 mg BID, or 24 mg QD for 36 weeks or 3 mg BID, 6 mg BID, or 12 mg BID (after amendment). Inflammatory Bowel Disease Questionnaire (IBDQ), European Quality of Life-5 Dimensions visual analog scale (EQ-5D VAS), and Work Productivity and Activity Impairment (WPAI) questionnaire outcomes were assessed at baseline and Weeks 8, 16, and 52. Results: At Week 16, a significant percentage (P ≤ 0.05) of patients receiving upadacitinib 6-mg BID dose or higher achieved IBDQ response (IBDQ score change ≥ 16 points; 49%–57% for upadacitinib vs. 24% for placebo) and IBDQ remission, except 24 mg QD (IBDQ score ≥ 170; 26%–39% for upadacitinib vs. 11% for placebo). Greater improvements in IBDQ total score, EQ-5D VAS, and activity impairment from baseline (P ≤ 0.1) versus placebo were also observed. Larger improvements (P ≤ 0.1) in IBDQ response and total score and EQ-5D VAS were observed at Week 8 with 6 and 24 mg BID versus placebo, with improvements for all dosages maintained or greater at Week 52 for IBDQ, EQ-5D VAS, and WPAI endpoints, in particular for the 12-mg BID group. Conclusion: Improvements in health-related quality of life and work productivity were achieved and sustained with upadacitinib in patients with moderate to severe Crohn’s disease. Trial Registration: ClinicalTrials.gov identifier, NCT02365649. © 2021, The Author(s). [less ▲]

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See detailReview article: distinctions between ileal and colonic Crohn's disease: from physiology to pathology.
Pierre, Nicolas ULiege; Salée, Catherine; Vieujean, Sophie et al

in Alimentary pharmacology & therapeutics (2021), 54(6), 779-791

BACKGROUND: Ileal and colonic Crohn's disease seem to be two separate entities. AIMS: To describe the main physiological distinctions between the small and the large intestine and to analyse the ... [more ▼]

BACKGROUND: Ileal and colonic Crohn's disease seem to be two separate entities. AIMS: To describe the main physiological distinctions between the small and the large intestine and to analyse the differences between ileal and colonic Crohn's disease. METHODS: The relevant literature was critically examined and synthesised. RESULTS: The small and large intestine have fundamental distinctions (anatomy, cellular populations, immune defence, microbiota). The differences between ileal and colonic Crohn's disease are highlighted by a heterogeneous body of evidence including clinical features (natural history of the disease, efficacy of treatments, and monitoring), epidemiological data (smoking status, age, gender) and biological data (genetics, microbiota, immunity, mesenteric fat). However, the contribution of these factors to disease location remains poorly understood. CONCLUSION: The classification of ileal and colonic Crohn's disease as distinct subphenotypes is well supported by the literature. Understanding of these differences could be exploited to develop more individualised patient care. [less ▲]

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