Publications by authors named "Pierre Ellul"

99 Publications

Regulatory T lymphocytes/Th17 lymphocytes imbalance in autism spectrum disorders: evidence from a meta-analysis.

Mol Autism 2021 Oct 12;12(1):68. Epub 2021 Oct 12.

AP-HP (Assistance Publique-Hôpitaux de Paris), Robert Debré Hospital, Child and Adolescent Psychiatry Department, Paris University, 48 Boulevard Sérurier, 75019, Paris, France.

Background: Immune system dysfunction has been proposed to play a critical role in the pathophysiology of autism spectrum disorders (ASD). Conflicting reports of lymphocyte subpopulation abnormalities have been described in numerous studies of patients with ASD. To better define lymphocytes abnormalities in ASD, we performed a meta-analysis of the lymphocyte profiles from subjects with ASD.

Methods: We used the PRISMA recommendations to query PubMed, Embase, PsychoINFO, BIOSIS, Science Direct, Cochrane CENTRAL, and Clinicaltrials.gov for terms related to clinical diagnosis of ASD and to lymphocytes' populations. We selected studies exploring lymphocyte subpopulations in children with ASD. The search protocol has been registered in the international Prospective Register of Systematic Reviews (CRD42019121473).

Results: We selected 13 studies gathering 388 ASD patients and 326 healthy controls. A significant decrease in the CD4+ lymphocyte was found in ASD patients compared to controls [- 1.51 (95% CI - 2.99; - 0.04) p = 0.04] (I = 96% [95% CI 94.6, 97.7], p < 0.01). No significant difference was found for the CD8+ T, B and natural killer lymphocytes. Considering the CD4+ subpopulation, there was a significant decrease in regulatory T lymphocytes (Tregs) in ASD patients (n = 114) compared to controls (n = 107) [- 3.09 (95% CI - 4.41; - 1.76) p = 0.0001]; (I = 90.9%, [95% CI 76.2, 96.5], p < 0.0001) associated with an increase oin the Th17 lymphocytes (ASD; n = 147 controls; n = 128) [2.23 (95% CI 0.79; 3.66) p = 0,002] (I = 95.1% [95% CI 90.4, 97.5], p < 0.0001).

Limitations: Several factors inducing heterogeneity should be considered. First, differences in the staining method may be responsible for a part in the heterogeneity of results. Second, ASD population is also by itself heterogeneous, underlying the need of studying sub-groups that are more homogeneous.

Conclusion: Our meta-analysis indicates defects in CD4+ lymphocytes, specifically decrease oin Tregs and increase in Th17 in ASD patients and supports the development of targeted immunotherapies in the field of ASD.
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http://dx.doi.org/10.1186/s13229-021-00472-4DOI Listing
October 2021

ECCO Guidelines on Therapeutics in Ulcerative Colitis: Surgical Treatment.

J Crohns Colitis 2021 Oct 12. Epub 2021 Oct 12.

Department of Surgery, Oncology and Gastroenterology, University of Padova, Padova, Italy.

This is the second of a series of two articles reporting the European Crohn's and Colitis Organisation [ECCO] evidence-based consensus on the management of adult patients with ulcerative colitis [UC]. The first article is focused on medical management and the present article addresses medical treatment of acute severe ulcerative colitis [ASUC] and surgical management of medically refractory UC patients, including preoperative optimization, surgical strategies, and technical issues. The article provides advice for a variety of common clinical and surgical conditions. Together, the articles represent an update of the evidence-based recommendations of the ECCO for UC.
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http://dx.doi.org/10.1093/ecco-jcc/jjab177DOI Listing
October 2021

Fever during pregnancy as a risk factor for neurodevelopmental disorders: results from a systematic review and meta-analysis.

Mol Autism 2021 09 18;12(1):60. Epub 2021 Sep 18.

Child and Adolescent Psychiatry Department, Robert Debré Hospital, APHP, Paris University, Paris, France.

Background: Fever during pregnancy is a relatively common and most often trivial event. However, under specific conditions, it could affect significantly fetal brain development. Few studies, with inconsistent results, investigated whether fever, regardless the pathogen, could represent a risk factor for neurodevelopmental disorders (NDD) in the offspring. We aimed to explore further this question by performing a systematic review and meta-analysis.

Methods: Peer-reviewed studies exploring the occurrence of NDD in offspring after a fetal exposure to maternal fever were included. We specifically considered the impact of fever severity and duration, taking into consideration some confounding variables such as the use of antipyretic during pregnancy, the trimester in which the fever arose, the maternal age or smoking at time of gestation. MEDLINE, EMBASE, PsycINFO, Cochrane and Web of Science were searched without language restriction. PRISMA recommendations were followed. Odds ratio (OR) were pooled using random-effects meta-analysis. Heterogeneity in effect size across studies was studied using random-effects meta-regression analysis. (PROSPERO CRD42020182801).

Results: We finally considered ten studies gathering a total of 10,304 children with NDD. Among them, 1394 were exposed to fever during pregnancy. The selected studies were divided into 5 case-control studies and 5 cohort studies. Maternal exposure to fever during pregnancy increased the risk of NDD in offspring with an OR of 1.24 [95% CI: 1.12-1.38]. Secondary analysis revealed an increased risk for NDD when fever occurred during the first trimester of gestation [OR 1.13-95% CI: 1.02-1.26].

Limitations: We excluded studies that considered infections with no evidence of fever. Another potential limitation may be the possible heterogeneity between study designs (cohorts and case-control).

Conclusion: Additional evidence supported the association between fever during pregnancy and increased risk for NDD in offspring. Careful monitoring should be considered for children born from mothers with a febrile episode during pregnancy (specifically during the first trimester).
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http://dx.doi.org/10.1186/s13229-021-00464-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8449704PMC
September 2021

Orofacial Granulomatosis associated with Crohn's Disease: a multi-centre case series.

J Crohns Colitis 2021 Sep 8. Epub 2021 Sep 8.

Department of Medicine, Division of Gastroenterology, Mater Dei hospital, Msida, Malta.

Background: Orofacial granulomatosis (OFG) is a rare syndrome that may be associated with Crohn's disease (CD). We aimed to characterise this relationship and the management options in the biologic era.

Methods: This multicentre case series was supported by the European Crohn's and Colitis Organisation (ECCO), and performed as part of the Collaborative Network of Exceptionally Rare case reports (CONFER) project. Clinical data were recorded in a standardised collection form.

Results: This report includes 28 patients with OFG associated with CD: 14 males (mean age of 32 years, ±12.4 SD) and 14 females (40.3 years, ±21.0 SD). Non-oral upper gastrointestinal tract involvement was seen in 6 cases and perianal disease in 11. The diagnosis of OFG was made prior to CD diagnosis in 2 patients, concurrently in 8 and after CD diagnosis in 18. The distribution of OFG involved the lips in 16 cases and buccal mucosa in 18. Pain was present in 25 cases, with impaired swallowing or speaking in 6. Remission was achieved in 23 patients, notably with the use of anti-TNFs in 9 patients, vedolizumab in 1, ustekinumab in 1 and thalidomide in 2. A further 5 cases were resistant to therapies including anti-TNFs.

Conclusion: OFG associated with CD may occur before, concurrently or after the diagnosis of CD. Perianal and UGI disease are common associations and there is a significant symptom burden in many. Remission can be obtained with a variety of immunosuppressive treatments, including several CD approved biologicals.
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http://dx.doi.org/10.1093/ecco-jcc/jjab158DOI Listing
September 2021

Implementation of European Society of Gastrointestinal Endoscopy (ESGE) recommendations for small-bowel capsule endoscopy into clinical practice: Results of an official ESGE survey.

Endoscopy 2021 09 28;53(9):970-980. Epub 2021 Jul 28.

Pomeranian Medical University, Department of Social Medicine and Public Health, Faculty of Health Science, Szczecin, Poland.

Background: We aimed to document international practices in small-bowel capsule endoscopy (SBCE), measuring adherence to European Society of Gastrointestinal Endoscopy (ESGE) technical and clinical recommendations.

Methods: Participants reached through the ESGE contact list completed a 52-item web-based survey.

Results: 217 responded from 47 countries (176 and 41, respectively, from countries with or without a national society affiliated to ESGE). Of respondents, 45 % had undergone formal SBCE training. Among SBCE procedures, 91 % were performed with an ESGE recommended indication, obscure gastrointestinal bleeding (OGIB), iron-deficiency anemia (IDA), and suspected/established Crohn's disease being the commonest and with higher rates of positive findings (49.4 %, 38.2 % and 53.5 %, respectively). A watchful waiting strategy after a negative SBCE for OGIB or IDA was preferred by 46.7 % and 70.3 %, respectively. SBCE was a second-line exam for evaluation of extent of new Crohn's disease for 62.2 % of respondents. Endoscopists adhered to varying extents to ESGE technical recommendations regarding bowel preparation ( > 60 %), use in those with pacemaker holders (62.5 %), patency capsule use (51.2 %), and use of a validated scale for bowel preparation assessment (13.3 %). Of the respondents, 67 % read and interpreted the exams themselves and 84 % classified exams findings as relevant or irrelevant. Two thirds anticipated future increase in SBCE demand. Inability to obtain tissue (78.3 %) and high cost (68.1 %) were regarded as the main limitations, and implementation of artificial intelligence as the top development priority (56.2 %).

Conclusions: To some extent, endoscopists follow ESGE guidelines on using SBCE in clinical practice. However, variations in practice have been identified, whose implications require further evaluation.
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http://dx.doi.org/10.1055/a-1541-2938DOI Listing
September 2021

A New Look on an Old Issue: Comprehensive Review of Neurotransmitter Studies in Cerebrospinal Fluid of Patients with Schizophrenia and Antipsychotic Effect on Monoamine's Metabolism.

Clin Psychopharmacol Neurosci 2021 Aug;19(3):395-410

Department of Psychiatry, Service Hospitalo Universitaire, Sainte Anne Hospital, Paris, France.

Neurotransmitters metabolism has a key role in the physiopathology of schizophrenia as demonstrated by studies measuring monoamine metabolites in patient's cerebrospinal fluid (CSF) since the beginning of the antipsychotic use. This comprehensive review aims to understand the anomalies of CSF monoamines in schizophrenia and their correlation with clinical and paraclinical features. We also review the influence of antipsychotic treatment on CSF monoamines and discuss the connection with metabolic and inflammatory processes. Studies comparing CSF homovanillic acid (HVA) levels between patients and controls are miscellaneous, due to the heterogeneity of samples studies. However, low HVA is associated with more positive symptoms and a poorer outcome and negatively correlated with brain ventricle size. Based on humans and animals' studies, antipsychotic treatments increase HVA during the first week of administration and decrease progressively over the time with a fall-off after withdrawal. 5-hydroxyindolacetic acetic acid levels do not seem to be different in the patient's CSF compared to controls. Considering metabolic co-factors of neurotransmitters synthesis, there is evidence supporting an increase of kynurenic acid in the CSF of patients with schizophrenia. Few studies explore folate metabolism in CSF. Literature also emphasizes the relationship between folate metabolism, inflammation and monoamine's metabolism. Those results suggest that the CSF monoamines could be correlated with schizophrenia symptoms and treatment outcome. However, further studies, exploring the role of CSF monoamines as biomarkers of disease severity and response to treatment are needed. They should assess the antipsychotic prescription, inflammatory markers and folate metabolism as potential confounding factors.
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http://dx.doi.org/10.9758/cpn.2021.19.3.395DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8316661PMC
August 2021

Identification of antibiotic resistance patterns in strains isolated from gastric biopsies using real-time PCR and genotypic analysis.

Ann Gastroenterol 2021 Jul-Aug;34(4):501-509. Epub 2021 Apr 2.

Department of Medicine (John Schembri, Anthea Pisani, Eliezer Zahra Bianco, James Gauci, Martina Muscat, Pierre Ellul).

Background: is associated with dyspepsia, mucus-associated lymphoid tissue lymphoma, gastritis, and peptic ulcer disease. Treatment in Malta consists of triple therapy, which consists of a proton pump inhibitor and 2 of the antibiotics amoxicillin, clarithromycin, metronidazole and fluoroquinolones. We aimed to determine the resistance rates for clarithromycin and fluoroquinolones in patients with , and its incidence, in patients undergoing an esophagogastroduodenoscopy (EGD) using real-time polymerase chain reaction (RT-PCR).

Methods: Patients undergoing an EGD were recruited. A rapid urease test (RUT) was performed, and 4 gastric biopsies were also taken (2 from antrum, 2 from corpus) and analyzed using RT-PCR. Positive samples were tested for antibiotic resistance using amplification and reverse hybridization techniques.

Results: Two hundred patients (mean age 53.6 [range 20-92] years; 53.1% female) were recruited; the majority were (78%) non-smokers. was identified in 21.0% of the patients. Fluoroquinolone resistance was detected in 21.4% of the patients. Clarithromycin resistance was observed in 26.2%, with dual resistance identified in 4.8% of the patients. A high concordance was present with patients testing negative for with both RUT and RT-PCR (94.3%). Only 57.6% of patients tested positive with both tests. However, 92.9% of RT-PCR positive patients had a positive genotype HelicoDR test.

Conclusions: This data demonstrates a high rate of resistance to both clarithromycin and fluoroquinolones. These should be avoided when treating by utilizing different treatment regimes. Furthermore, we derived important data on the role of RT-PCR, which may be implemented in routine clinical practice.
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http://dx.doi.org/10.20524/aog.2021.0624DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8276370PMC
April 2021

The Impact of the SARS-CoV-2 (COVID-19) Pandemic on Gastroenterology Training.

GE Port J Gastroenterol 2021 Apr 28;92:1-6. Epub 2021 Apr 28.

Division of Gastroenterology, Mater Dei Hospital, Mosta, Malta.

Introduction: The SARS-CoV-2 (COVID-19) pandemic has brought about a radical change in our working patterns. These changes can affect the training that gastroenterology trainees undergo, especially endoscopy since these are aerosol-generating procedures. The aim of this survey was to assess the effect of the COVID-19 pandemic on gastroenterology training across the European countries.

Methodology: A questionnaire was set up whereby the different elements of training were analysed. The questionnaire (online) was distributed among trainees through the National Representatives of the European Board of Gastroenterology and Hepatology.

Results: In total, 86 trainees (females: 55%; mean age: 32.5 years [SD ±4.57 years]; mean training duration of 2.68 years [SD ±1.63]) from 22 different countries were recruited. From the cohort, 10.5% were considered as vulnerable for acquiring COVID-19. During their job, 4.7% acquired the infection and 26.7% were placed in quarantine. Most trainees noted that their various aspects of gastroenterology training were moderately or severely affected during the initial height of the pandemic: clinical gastroenterology training (67.4%), outpatients (75.5%), didactic teaching (88.3%), multidisciplinary team meetings (65.2%) and endoscopy training (75.6%). Later, when the number of COVID-19-related infections decreased across Europe, the above modalities returned to normal for <50% of the trainees.

Conclusion: This European-wide survey has demonstrated that gastroenterology training has been severely impacted during both the initial height of the pandemic and afterwards. Furthermore, the psychological impact on trainees, in terms of training quality, duration and exposure to COVID-19, is unknown. A re-assessment of each centre training programme should be done as to ensure that a high standard of training is still being delivered.
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http://dx.doi.org/10.1159/000515408DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8247833PMC
April 2021

Safety of gastrointestinal endoscopy during the COVID-19 pandemic: A new quality indicator?

Dig Liver Dis 2021 09 26;53(9):1073-1075. Epub 2021 Jun 26.

Division of Gastroenterology, Mater Dei Hospital, MSD 2090, Msida, Malta. Electronic address:

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http://dx.doi.org/10.1016/j.dld.2021.06.018DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8233848PMC
September 2021

ECCO Topical Review: Refractory Inflammatory Bowel Disease.

J Crohns Colitis 2021 Oct;15(10):1605-1620

Centre for Colorectal Disease, St Vincent's University Hospital and School of Medicine, University College Dublin, Gastroenterology, Dublin, Ireland.

Inflammatory bowel disease is a chronic disease with variable degrees of extent, severity, and activity. A proportion of patients will have disease that is refractory to licensed therapies, resulting in significant impairment in quality of life. The treatment of these patients involves a systematic approach by the entire multidisciplinary team, with particular consideration given to medical options including unlicensed therapies, surgical interventions, and dietetic and psychological support. The purpose of this review is to guide clinicians through this process and provide an accurate summary of the available evidence for different strategies.
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http://dx.doi.org/10.1093/ecco-jcc/jjab112DOI Listing
October 2021

Scoring Systems for Clinical Colon Capsule Endoscopy-All You Need to Know.

J Clin Med 2021 May 28;10(11). Epub 2021 May 28.

Gastroenterology Department, Mater Dei Hospital, MSD 2090 Msida, Malta.

In the constantly developing era of minimal diagnostic invasiveness, the role of colon capsule endoscopy in colonic examination is being increasingly recognised, especially in the context of curtailed endoscopy services due to the COVID-19 pandemic. It is a safe diagnostic tool with low adverse event rates. As with other endoscopic modalities, various colon capsule endoscopy scores allow the standardisation of reporting and reproducibility. As bowel cleanliness affects CCE's diagnostic yield, a few operator-dependent scores (Leighton-Rex and CC-CLEAR scores) and a computer-dependent score (CAC score) have been developed to grade bowel cleanliness objectively. CCE can be used to monitor IBD mucosal disease activity through the UCEIS and the panenteric CECDAIic score for UC and CD, respectively. CCE may also have a role in CRC screening, given similar sensitivity and specificity rates to conventional colonoscopy to detect colonic polyps ≥ 10 mm and CRC. Given CCE's diagnostic yield and reproducible clinical scores with high inter-observer agreements, CCE is fast becoming a suitable alternative to conventional colonoscopy in specific patient populations.
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http://dx.doi.org/10.3390/jcm10112372DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8199426PMC
May 2021

A Rare Case of PEComa of the Liver.

GE Port J Gastroenterol 2021 Apr 5;28(3):217-221. Epub 2020 Oct 5.

Division of Gastroenterology, Mater Dei Hospital, Triq id-Donaturi tad-Demm, Msida, Malta.

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http://dx.doi.org/10.1159/000509192DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8138188PMC
April 2021

Validation and Update of the Lémann Index to Measure Cumulative Structural Bowel Damage in Crohn's Disease.

Gastroenterology 2021 Sep 28;161(3):853-864.e13. Epub 2021 May 28.

INSERM U1135 Centre de Recherche Epidémiologie et Statistiques, Equipe Epidemiology and Clinical Statistics for Tumor, Respiratory, and Resuscitation Assessments, Université de Paris, Hôpital Saint-Louis, Paris, France.

Background & Aims: The Lémann Index is a tool measuring cumulative structural bowel damage in Crohn's disease (CD). We reported on its validation and updating.

Methods: This was an international, multicenter, prospective, cross-sectional observational study. At each center, 10 inclusions, stratified by CD duration and location, were planned. For each patient, the digestive tract was divided into 4 organs, upper tract, small bowel, colon/rectum, anus, and subsequently into segments, explored systematically by magnetic resonance imaging and by endoscopies in relation to disease location. For each segment, investigators retrieved information on previous surgical procedures, identified predefined strictures and penetrating lesions of maximal severity (grades 1-3) at each organ investigational method (gastroenterologist and radiologist for magnetic resonance imaging), provided segmental damage evaluation ranging from 0.0 to 10.0 (complete resection). Organ resection-free cumulative damage evaluation was then calculated from the sum of segmental damages. Then investigators provided a 0-10 global damage evaluation from the 4-organ standardized cumulative damage evaluations. Simple linear regressions of investigator damage evaluations on their corresponding Lémann Index were studied, as well as calibration plots. Finally, updated Lémann Index was derived through multiple linear mixed models applied to combined development and validation samples.

Results: In 15 centers, 134 patients were included. Correlation coefficients between investigator damage evaluations and Lémann Indexes were >0.80. When analyzing data in 272 patients from both samples and 27 centers, the unbiased correlation estimates were 0.89, 0,97, 0,94, 0.81, and 0.91 for the 4 organs and globally, and stable when applied to one sample or the other.

Conclusions: The updated Lémann Index is a well-established index to assess cumulative bowel damage in CD that can be used in epidemiological studies and disease modification trials.
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http://dx.doi.org/10.1053/j.gastro.2021.05.049DOI Listing
September 2021

Histological Inflammation in the Endoscopically Uninflamed Mucosa is Associated With Worse Outcomes in Limited Ulcerative Colitis.

Inflamm Bowel Dis 2021 May 17. Epub 2021 May 17.

Gastroenterology Division, Hospital Beatriz Ângelo, Loures, Portugal.

Background: The Montreal classification categorizes patients with ulcerative colitis (UC) based on their macroscopic disease extent. Independent of endoscopic extent, biopsies through all colonic segments should be retrieved during index colonoscopy. However, the prognostic value of histological inflammation at diagnosis in the inflamed and uninflamed regions of the colon has never been assessed.

Methods: This was a multicenter retrospective cohort study of newly diagnosed patients with treatment-naïve proctitis and left-sided UC. Biopsies from at least 2 colonic segments (endoscopically inflamed and uninflamed mucosa) were retrieved and reviewed by 2 pathologists. Histological features in the endoscopically inflamed and uninflamed mucosa were scored using the Nancy score. The primary outcomes were disease complications (proximal disease extension, need for hospitalization or colectomy) and higher therapeutic requirements (need for steroids or for therapy escalation).

Results: Overall, 93 treatment-naïve patients were included, with a median follow-up of 44 months (range, 2-329). The prevalence of any histological inflammation above the endoscopic margin was 71%. Proximal disease extension was more frequent in patients with histological inflammation in the endoscopically uninflamed mucosa at diagnosis (21.5% vs 3.4%, P = 0.04). Histological involvement above the endoscopic margin was the only predictor associated with an earlier need for therapy escalation (adjusted hazard ratio, 3.69; 95% confidence interval, 1.05-13.0); P = 0.04) and disease complications (adjusted hazard ratio, 4.79; 95% confidence interval, 1.10-20.9; P = 0.04).

Conclusions: The presence of histological inflammation in the endoscopically uninflamed mucosa at the time of diagnosis was associated with worse outcomes in limited UC.
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http://dx.doi.org/10.1093/ibd/izab069DOI Listing
May 2021

Conjugal inflammatory bowel disease: a systematic review and European survey.

Ann Gastroenterol 2021 26;34(3):361-369. Epub 2021 Feb 26.

Division of Gastroenterology, Hospital Beatriz Ângelo, Loures, Portugal (Maria Pia Costa-Santos, Catarina Frias-Gomes, António Oliveira, Joana Torres).

Background: The frequency of inflammatory bowel disease (IBD) is increased after marriage to an individual with the disease. Importantly, the offspring of these couples have a significant risk for developing the disease. Herein, we aimed to better characterize conjugal IBD.

Methods: A systematic literature search was conducted with predetermined search criteria. Relevant manuscripts reporting on couples with IBD and their offspring were selected. Concomitantly, a cross-sectional survey was conducted of couples where both members were affected with IBD, as well as their offspring, and electronically distributed by patients' associations.

Results: We identified 20 reports of IBD in couples, for a total of 68 couples. Of these, 66% were concordant regarding IBD type and 66% were diagnosed after cohabitation. The overall prevalence of IBD in the offspring of these couples was 29%. Our survey identified 58 couples with IBD, with 62% being concordant regarding IBD type; 42.9% were diagnosed prior to cohabitation, in 12.5% one spouse was diagnosed before and the other after cohabitation, and in 44.6% the onset of disease occurred after cohabitation for both. The prevalence of IBD in children born from these couples was 10%. The probability of developing disease in the progeny was 2% at 10 years, 12% at 15 years, and 16% at 20 years of age.

Conclusions: IBD in couples occurs mostly after marriage to an individual with disease or after many years of cohabitation. In a modern cohort, the risk for the progeny was around 16% by the age of 20, lower than previously reported.
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http://dx.doi.org/10.20524/aog.2021.0598DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8079879PMC
February 2021

Results of the Seventh Scientific Workshop of ECCO: Precision Medicine in IBD - Challenges and Future Directions.

J Crohns Colitis 2021 09;15(9):1407-1409

Translational & Clinical Research Institute, Faculty of Medical Sciences, Newcastle University, Newcastle upon Tyne, UK.

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http://dx.doi.org/10.1093/ecco-jcc/jjab049DOI Listing
September 2021

Prevalence, Behaviours and Burden of Irritable Bowel Syndrome in Medical Students and Junior Doctors.

Ulster Med J 2021 Jan 26;90(1):16-21. Epub 2021 Feb 26.

35, Triq San Pacifiku, Mosta, MST 1220, Malta. 00356 79297926.

Background: Irritable bowel syndrome (IBS) is a common functional gastrointestinal disorder which can have a strong impact on patients' quality of life including influence on various social aspects and psychological ramifications. The aim of the study was to assess the prevalence and consequences of IBS in medical students and junior doctors in Malta.

Method: An online survey was sent out to all medical students enrolled at University of Malta and all doctors training with the Malta Foundation Programme.

Key Results: The prevalence of IBS was 17.7% (total number =192), with 6.2% being previously diagnosed with IBS and the rest (11.5%) having symptoms consistent with IBS according to the Rome IV criteria. There was no statistically significant difference in BMI and in activity level as determined by the Godin Leisure-Time Exercise Questionnaire between IBS and non-IBS group.Absenteeism was significantly commoner in students/ doctors with IBS (47.1%) than in those without IBS (9.5%; p=0.0001). Of those previously diagnosed with IBS, 66.7% self-medicated compared to 45.4% of those diagnosed through the questionnaire. 71.6% of those in the IBS group tried dietary modification as to control their symptoms.On the Kessler 6 Distress scale, 91.2% of the IBS group had a score >6, with 44.1% having a score >13. The mean Visceral Sensitivity Index Score was 40.1 (95% CI 33.6 - 46.6).

Conclusion: IBS is prevalent, yet under-recognized, in medical students and junior doctors. Measures should be instituted for timely, confidential detection and management of IBS and its related psychological consequences.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7907899PMC
January 2021

Prevalence, Behaviours and Burden of Irritable Bowel Syndrome in Medical Students and Junior Doctors.

Ulster Med J 2021 Jan 26;90(1):16-21. Epub 2021 Feb 26.

35, Triq San Pacifiku, Mosta, MST 1220, Malta. 00356 79297926.

Background: Irritable bowel syndrome (IBS) is a common functional gastrointestinal disorder which can have a strong impact on patients' quality of life including influence on various social aspects and psychological ramifications. The aim of the study was to assess the prevalence and consequences of IBS in medical students and junior doctors in Malta.

Method: An online survey was sent out to all medical students enrolled at University of Malta and all doctors training with the Malta Foundation Programme.

Key Results: The prevalence of IBS was 17.7% (total number =192), with 6.2% being previously diagnosed with IBS and the rest (11.5%) having symptoms consistent with IBS according to the Rome IV criteria. There was no statistically significant difference in BMI and in activity level as determined by the Godin Leisure-Time Exercise Questionnaire between IBS and non-IBS group.Absenteeism was significantly commoner in students/ doctors with IBS (47.1%) than in those without IBS (9.5%; p=0.0001). Of those previously diagnosed with IBS, 66.7% self-medicated compared to 45.4% of those diagnosed through the questionnaire. 71.6% of those in the IBS group tried dietary modification as to control their symptoms.On the Kessler 6 Distress scale, 91.2% of the IBS group had a score >6, with 44.1% having a score >13. The mean Visceral Sensitivity Index Score was 40.1 (95% CI 33.6 - 46.6).

Conclusion: IBS is prevalent, yet under-recognized, in medical students and junior doctors. Measures should be instituted for timely, confidential detection and management of IBS and its related psychological consequences.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7907899PMC
January 2021

Transethnic analysis of the human leukocyte antigen region for ulcerative colitis reveals not only shared but also ethnicity-specific disease associations.

Hum Mol Genet 2021 04;30(5):356-369

Schools of Mathematics and Statistics and BioSciences and Melbourne Integrative Genomics, University of Melbourne, Victoria 3010, Australia.

Inflammatory bowel disease (IBD) is a chronic inflammatory disease of the gut. Genetic association studies have identified the highly variable human leukocyte antigen (HLA) region as the strongest susceptibility locus for IBD and specifically DRB1*01:03 as a determining factor for ulcerative colitis (UC). However, for most of the association signal such as delineation could not be made because of tight structures of linkage disequilibrium within the HLA. The aim of this study was therefore to further characterize the HLA signal using a transethnic approach. We performed a comprehensive fine mapping of single HLA alleles in UC in a cohort of 9272 individuals with African American, East Asian, Puerto Rican, Indian and Iranian descent and 40 691 previously analyzed Caucasians, additionally analyzing whole HLA haplotypes. We computationally characterized the binding of associated HLA alleles to human self-peptides and analyzed the physicochemical properties of the HLA proteins and predicted self-peptidomes. Highlighting alleles of the HLA-DRB1*15 group and their correlated HLA-DQ-DR haplotypes, we not only identified consistent associations (regarding effects directions/magnitudes) across different ethnicities but also identified population-specific signals (regarding differences in allele frequencies). We observed that DRB1*01:03 is mostly present in individuals of Western European descent and hardly present in non-Caucasian individuals. We found peptides predicted to bind to risk HLA alleles to be rich in positively charged amino acids. We conclude that the HLA plays an important role for UC susceptibility across different ethnicities. This research further implicates specific features of peptides that are predicted to bind risk and protective HLA proteins.
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http://dx.doi.org/10.1093/hmg/ddab017DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8098114PMC
April 2021

Differential Expression of Interferon-Alpha Protein Provides Clues to Tissue Specificity Across Type I Interferonopathies.

J Clin Immunol 2021 04 7;41(3):603-609. Epub 2021 Jan 7.

General Paediatrics- Infectious Diseases and Internal Medicine Department, Robert-Debré Hospital, AP-HP, Nord - Université de Paris, Paris, France.

Whilst upregulation of type I interferon (IFN) signaling is common across the type I interferonopathies (T1Is), central nervous system (CNS) involvement varies between these disorders, the basis of which remains unclear. We collected cerebrospinal fluid (CSF) and serum from patients with Aicardi-Goutières syndrome (AGS), STING-associated vasculopathy with onset in infancy (SAVI), presumed monogenic T1Is (pT1I), childhood systemic lupus erythematosus with neuropsychiatric features (nSLE), non-IFN-related autoinflammation (AI) and non-inflammatory hydrocephalus (as controls). We measured IFN-alpha protein using digital ELISA. Eighty-two and 63 measurements were recorded respectively in CSF and serum of 42 patients and 6 controls. In an intergroup comparison (taking one sample per individual), median CSF IFN-alpha levels were elevated in AGS, SAVI, pT1I, and nSLE compared to AI and controls, with levels highest in AGS compared to all other groups. In AGS, CSF IFN-alpha concentrations were higher than in paired serum samples. In contrast, serum IFN was consistently higher compared to CSF levels in SAVI, pT1I, and nSLE. Whilst IFN-alpha is present in the CSF and serum of all IFN-related diseases studied here, our data suggest the primary sites of IFN production in the monogenic T1I AGS and SAVI are, respectively, the CNS and the periphery. These results inform the diagnosis of, and future therapeutic approaches to, monogenic and multifactorial T1Is.
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http://dx.doi.org/10.1007/s10875-020-00952-xDOI Listing
April 2021

Patients with Inflammatory Bowel Disease Are Not at Increased Risk of COVID-19: A Large Multinational Cohort Study.

J Clin Med 2020 Oct 31;9(11). Epub 2020 Oct 31.

Department of Biomedical Sciences, Humanitas University, Via Rita Levi Montalcini 4, 20090 Pieve Emanuele, Milan, Italy.

The impact of COVID-19 on inflammatory bowel disease (IBD) patients under pharmacological immunosuppression is still not clearly understood. We investigated the incidence of COVID-19 and the impact of immunosuppression and containment measures on the risk of SARS-CoV-2 infection in a large IBD cohort, from a multicenter cohort from 21st of February to 30th of June, 2020. Ninety-seven patients with IBD (43 UC, 53 CD, one unclassified IBD) and concomitant COVID-19 over a total of 23,879 patients with IBD were enrolled in the study. The cumulative incidence of SARS-CoV-2 infection in patients with IBD vs. the general population was 0.406% and 0.402% cases, respectively. Twenty-three patients (24%) were hospitalized, 21 (22%) had pneumonia, four (4%) were admitted to the Intensive Care Unit, and one patient died. Lethality in our cohort was 1% compared to 9% in the general population. At multivariable analysis, age > 65 years was associated with increased risk of pneumonia and hospitalization (OR 11.6, 95% CI 2.18-62.60; OR 5.1, 95% CI 1.10-23.86, respectively), treatment with corticosteroids increased the risk of hospitalization (OR 7.6, 95% CI 1.48-40.05), whereas monoclonal antibodies were associated with reduced risk of pneumonia and hospitalization (OR 0.1, 95% CI 0.04-0.52; OR 0.3, 95% CI 0.10-0.90, respectively). The risk of COVID-19 in patients with IBD is similar to the general population. National lockdown was effective in preventing infection in our cohort. Advanced age and treatment with corticosteroids impacted negatively on the outcome of COVID-19, whereas monoclonal antibodies did not seem to have a detrimental effect.
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http://dx.doi.org/10.3390/jcm9113533DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7693947PMC
October 2020

Diverticular Disease: A Review on Pathophysiology and Recent Evidence.

Ulster Med J 2020 Sep 21;89(2):83-88. Epub 2020 Oct 21.

: Mater Dei Hospital, Valletta, Malta.

Diverticular disease is common condition globally, especially in Western countries. Diverticulitis, Symptomatic uncomplicated Diverticular disease and Segmental Colitis associated with diverticula constitute diverticular disease. Although most patients with diverticula are asymptomatic, around 25% of patients will experience symptoms whilst 5% of patients have an episode of acute diverticulitis. The prevalence increases with age with more than one theory being put forward to explain its pathogenesis. Faecolith entrapment in diverticula results in colonic mucosal damage and oedema, bacterial proliferation and toxin accumulation leading to perforation. This mechanism may explain diverticulitis in elderly patients with multiple, larger diverticula. Ischaemic damage could be the cause of acute diverticulitis in younger patients with sparse diverticula where more frequent and forceful muscular contractions in response to colonic stimuli occlude the vasculature leading to ischaemia and microperforation. Chronic colonic active inflammation in the presence of diverticular disease is termed Segmental colitis associated with diverticulosis. Its pathophysiology is still indeterminate but together with its clinical picture, may mimic Inflammatory Bowel Disease. Treatment includes a high fibre diet together with antibiotics and/or salicylates with surgery in severe cases. Indications for elective surgery in diverticular disease have changed over the past decades as this may not suggest a reduction in morbidity and mortality. Prophylaxis with probiotics, laxatives, anti-spasmotics, anticholinergic drugs and salicylates are at the centre of recent studies. Studies are also challenging previously believed facts regarding dietary fibre, nuts and seeds whilst emphasizing the effect of healthy lifestyle and smoking on the increasing incidence of DD.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7576390PMC
September 2020

Panenteric capsule endoscopy identifies proximal small bowel disease guiding upstaging and treatment intensification in Crohn's disease: A European multicentre observational cohort study.

United European Gastroenterol J 2021 03 19;9(2):248-255. Epub 2021 Mar 19.

Academic Department of Gastroenterology and Hepatology, Sheffield Teaching Hospitals NHS Trust, Sheffield, UK.

Background: Endoscopically defined mucosal healing in Crohn's disease is associated with improved outcomes. Panenteric capsule endoscopy enables a single non-invasive assessment of small and large bowel mucosal inflammation.

Aims And Methods: This multicentre observational study of patients with suspected and established Crohn's disease examined the feasibility, safety and impact on patient outcomes of panenteric capsule endoscopy in routine clinical practice. The potential role in assessment of disease severity and extent by a comparison with existing clinical and biochemical markers is examined.

Results: Panenteric capsule endoscopy was performed on 93 patients (71 with established and 22 with suspected Crohn's disease). A complete examination occurred in 85% (79/93). Two cases (2.8%) of capsule retention occurred in patients with established Crohn's disease. Panenteric capsule resulted in management change in 38.7% (36/93) patients, including 64.6% (32/48) of those with an established diagnosis whose disease was active, and all three patients with newly diagnosed Crohn's disease. Montreal classification was upstaged in 33.8% of patients with established Crohn's disease and mucosal healing was demonstrated in 15.5%. Proximal small bowel disease upstaged disease in 12.7% and predicted escalation of therapy (odds ratio 40.3, 95% confidence interval 3.6-450.2). Raised C-reactive protein and faecal calprotectin were poorly sensitive in detecting active disease (0.48 and 0.59 respectively).

Conclusions: Panenteric capsule endoscopy was feasible in routine practice and the ability to detect proximal small bowel disease may allow better estimation of prognosis and guide treatment intensification. Panenteric capsule endoscopy may be a suitable non-invasive endoscopic investigation in determining disease activity and supporting management decisions.
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http://dx.doi.org/10.1177/2050640620948664DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8259365PMC
March 2021

The use of 5-aminosalicylate for patients with Crohn's disease in a prospective European inception cohort with 5 years follow-up - an Epi-IBD study.

United European Gastroenterol J 2020 10 26;8(8):949-960. Epub 2020 Jul 26.

Hull University Teaching Hospitals NHS Trust, Hull, UK.

Background: The lack of scientific evidence regarding the effectiveness of 5-aminosalicylate in patients with Crohn's disease is in sharp contrast to its widespread use in clinical practice.

Aims: The aim of the study was to investigate the use of 5-aminosalicylate in patients with Crohn's disease as well as the disease course of a subgroup of patients who were treated with 5-aminosalicylate as maintenance monotherapy during the first year of disease.

Methods: In a European community-based inception cohort, 488 patients with Crohn's disease were followed from the time of their diagnosis. Information on clinical data, demographics, disease activity, medical therapy and rates of surgery, cancers and deaths was collected prospectively. Patient management was left to the discretion of the treating gastroenterologists.

Results: Overall, 292 (60%) patients with Crohn's disease received 5-aminosalicylate period during follow-up for a median duration of 28 months (interquartile range 6-60). Of these, 78 (16%) patients received 5-aminosalicylate monotherapy during the first year following diagnosis. Patients who received monotherapy with 5-aminosalicylate experienced a mild disease course with only nine (12%) who required hospitalization, surgery, or developed stricturing or penetrating disease, and most never needed more intensive therapy. The remaining 214 patients were treated with 5-aminosalicylate as the first maintenance drug although most eventually needed to step up to other treatments including immunomodulators (75 (35%)), biological therapy (49 (23%)) or surgery (38 (18%)).

Conclusion: In this European community-based inception cohort of unselected Crohn's disease patients, 5-aminosalicylate was commonly used. A substantial group of these patients experienced a quiescent disease course without need of additional treatment during follow-up. Therefore, despite the controversy regarding the efficacy of 5-aminosalicylate in Crohn's disease, its use seems to result in a satisfying disease course for both patients and physicians.
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http://dx.doi.org/10.1177/2050640620945949DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7707880PMC
October 2020

Immune Activation and Deficit in Neurotransmitters Synthesis in Treatment Resistant Depression: About a Case of Hashimoto Encephalopathy.

Clin Psychopharmacol Neurosci 2020 Aug;18(3):463-466

Centre Hospitalier Sainte-Anne, Faculty of Medicine Paris Descartes, Service Hospitalo-Universitaire, Paris, France.

We report a case of Hashimoto encephalopathy initially presented as a drug-resistant depression with predominant apathy and asthenia, successfully treated with cyclophosphamide. We suspected that the psychiatric symptoms were due to a deficit in neurotransmitter synthesis related to immune activation. We hypothesized that the immunomodulatory treatment helped to restore the neurotransmitter synthesis and thus decreased the patient's depressive symptoms. In this case report we propose an innovative model in which immunity might disturbs neurotransmitters synthesis leading to depressive symptoms.
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http://dx.doi.org/10.9758/cpn.2020.18.3.463DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7383012PMC
August 2020

High diagnostic value of plasma Niemann-Pick type C biomarkers in adults with selected neurological and/or psychiatric disorders.

J Neurol 2020 Nov 26;267(11):3371-3377. Epub 2020 Jun 26.

Neurology Department, Reference Center for Lysosomal Diseases, Neurogenetics and Metabolism Unit, Hôpital Pitié-Salpêtrière, 47-83 boulevard de l'Hôpital, 75013, Paris, France.

Late-onset Niemann-Pick type C (NP-C) is a rare, underdiagnosed lysosomal disease with neurological manifestations. A specific treatment, miglustat, can stabilize the disease if given early. Recently, three plasma screening biomarkers (PSBs) were developed [cholestane3β,5α,6βtriol (C-triol), 7-ketocholesterol (7-KC), and lysosphingomyelin-509 (LSM-509)], allowing a simpler and quite robust screening of patients suitable for genetic testing. The objective of our study was to evaluate practical utility and feasibility of large-scale PSB screening for NP-C in selected adult patients. Patients were prospectively enrolled if they showed, starting from 12 years of age, at least one of the three initial neuro-psychiatric manifestations described in NP-C: (1) gait disorder (cerebellar and/or dystonic); (2) cognitive decline with frontal lobe syndrome; (3) atypical psychosis. PSBs were measured in plasma of all patients and, if positive (LSM-509 and/or C-triol + 7-KC elevated), sequencing of NPC1 and NPC2 genes was performed. A total of 251 patients [136 males, 115 females; median age 42.1 (range 12.2-85.6) years] were screened. Six patients had positive PSBs. Two were confirmed to have NP-C (0.8% diagnostic yield, both with all three PSBs highly increased, especially LSM-509). False-positive rate was 1.2%, which was identical if only considering LSM-509. By contrast, false-positive rates were 8.1% and 5.7% for 7-KC and C-triol, respectively. We showed that selecting patients with neurologic and/or psychiatric symptoms consistent with NP-C for large-scale PSB screening is a simple and valid strategy to identify new adult NP-C patients, and would probably lead to earlier diagnosis and treatment administration if widely applied.
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http://dx.doi.org/10.1007/s00415-020-10020-4DOI Listing
November 2020

Catatonia in a patient with Aicardi-Goutières syndrome efficiently treated with immunoadsorption.

Schizophr Res 2020 08 19;222:484-486. Epub 2020 Jun 19.

INSERM UMR 1163, Laboratoire de Neurogénétique et Neuroinflammation, Paris, France; Service de Pédiatrie Générale, Maladies Infectieuses et Médecine Interne, Centre de référence des rhumatismes inflammatoires et maladies autoimmunes systémiques rares de l'enfant (RAISE), APHP Robert Debré, Paris, France; Service d'Immunologie-Hématologie et Rhumatologie Pédiatriques, APHP Necker-Enfants Malades, Paris, France.

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http://dx.doi.org/10.1016/j.schres.2020.05.064DOI Listing
August 2020
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