Comments and Illustrations of Ultrasound Findings in Extrapulmonary Tuberculosis Manifestations.

This review describes the appearance of extrapulmonary tuberculosis manifestations in comprehensive and multiparametric ultrasound imaging. The aim is to increase awareness of typical ultrasound findings regarding extrapulmonary tuberculosis, correlate those with pathological features, and facilitate differential diagnosis. Point of care ultrasound protocols can be used as a screening method in high-risk populations, although the negative findings do not exclude tuberculosis. Conversely, the diagnosis of extrapulmonary tuberculosis can never be made using ultrasound alone, as many ultrasound findings in extrapulmonary tuberculosis are non-specific. However, ultrasound-based sampling techniques can significantly facilitate the collection of samples for microbiological or molecular proof of tuberculosis, as well as facilitating the establishment of alternative diagnoses.

Development of non-alcoholic steatohepatitis is associated with gut microbiota but not with oxysterol enzymes CH25H, EBI2, or CYP7B1 in mice.

Liver steatosis is the most frequent liver disorder and its advanced stage, non-alcoholic steatohepatitis (NASH), will soon become the main reason for liver fibrosis and cirrhosis. The "multiple hits hypothesis" suggests that progression from simple steatosis to NASH is triggered by multiple factors including the gut microbiota composition. The Epstein Barr virus induced gene 2 (EBI2) is a receptor for the oxysterol 7a, 25-dihydroxycholesterol synthesized by the enzymes CH25H and CYP7B1. EBI2 and its ligand control activation of immune cells in secondary lymphoid organs and the gut. Here we show a concurrent study of the microbial dysregulation and perturbation of the EBI2 axis in a mice model of NASH.We used mice with wildtype, or littermates with CH25H-/-, EBI2-/-, or CYP7B1-/- genotypes fed with a high-fat diet (HFD) containing high amounts of fat, cholesterol, and fructose for 20 weeks to induce liver steatosis and NASH. Fecal and small intestinal microbiota samples were collected, and microbiota signatures were compared according to genotype and NASH disease state.We found pronounced differences in microbiota composition of mice with HFD developing NASH compared to mice did not developing NASH. In mice with NASH, we identified significantly increased 33 taxa mainly belonging to the Clostridiales order and/ or the family, and significantly decreased 17 taxa. Using an Elastic Net algorithm, we suggest a microbiota signature that predicts NASH in animals with a HFD from the microbiota composition with moderate accuracy (area under the receiver operator characteristics curve = 0.64). In contrast, no microbiota differences regarding the studied genotypes (wildtype vs knock-out CH25H-/-, EBI2-/-, or CYP7B1-/-) were observed.In conclusion, our data confirm previous studies identifying the intestinal microbiota composition as a relevant marker for NASH pathogenesis. Further, no link of the EBI2 - oxysterol axis to the intestinal microbiota was detectable in the current study.

Immune activation and inflammation in lactating women on combination antiretroviral therapy: role of gut dysfunction and gut microbiota imbalance.

Introduction: Combination antiretroviral therapy (cART) effectively controls HIV; however, chronic low-level viremia and gut microbiota dysbiosis remain significant drivers of gut and systemic inflammation. In this study, we explored the relationship between gut microbiota composition, intestinal inflammation, microbial translocation, and systemic inflammation in women on cART in Sub-Saharan Africa. Methods: We conducted a study in HIV-infected and HIV-uninfected lactating women followed up at 6 weeks and 6 months postpartum in Harare, Zimbabwe. We used 16S ribosomal Ribonucleic Acid (rRNA) sequencing and MesoScale Discovery V-Plex assays to examine the gut microbiome and to quantify plasma inflammatory biomarkers, respectively. In addition, we measured fecal calprotectin, plasma lipopolysaccharide-binding protein (LBP), and soluble cluster of differentiation 14 (sCD14) by enzyme-linked immunosorbent assay to assess gut inflammation, microbial translocation, and monocyte/macrophage activation. Results: A group of 77 lactating women were studied, of which 35% were HIV-infected. Fecal calprotectin levels were similar by HIV status at both follow-up time points. In the HIV-infected group at 6 weeks postpartum, fecal calprotectin was elevated: median (interquartile range) [158.1 µg/g (75.3-230.2)] in women who had CD4+ T-lymphocyte counts <350 cells/µL compared with those with ≥350 cells/µL [21.1 µg/g (0-58.4)], p = 0.032. Plasma sCD14 levels were significantly higher in the HIV-infected group at both 6 weeks and 6 months postpartum, p < 0.001. Plasma LBP levels were similar, but higher levels were observed in HIV-infected women with elevated fecal calprotectin. We found significant correlations between fecal calprotectin, LBP, and sCD14 with proinflammatory cytokines. Gut microbial alpha diversity was not affected by HIV status and was not affected by use of antibiotic prophylaxis. HIV significantly affected microbial beta diversity, and significant differences in microbial composition were noted. The genera Slackia and Collinsella were relatively more abundant in the HIV-infected group, whereas a lower relative abundance of Clostriduim sensu_stricto_1 was observed. Our study also found correlations between gut microbial taxa abundance and systemic inflammatory biomarkers. Discussion and conclusion: HIV-infected lactating women had increased immune activation and increased microbial translocation associated with increased gut inflammation. We identified correlations between the gut inflammation and microbial composition, microbial translocation, and systemic inflammation. The interplay of these parameters might affect the health of this vulnerable population.

[Overview and therapy update Crohn's disease].

INTRODUCTION: Crohn's disease (CD) is a chronic inflammatory bowel disease that can affect the entire gastrointestinal tract. The pathophysiology of CD includes a disrupted interplay of intestinal bacteria, the intestinal immune system and the intestinal surface in genetically susceptible individuals, which remains incompletely understood. Conventional therapies include steroids, but numerous advanced therapies are also available. Three tumor necrosis factor (TNF) inhibitors (infliximab, adalimumab and certolizumab pegol (Switzerland)) have been approved for MC. Additional treatment options include the interleukin (IL)-12/23 inhibitors ustekinumab and the integrin inhibitors vedolizumab. With risankizumab, a first selective IL-23 inhibitor for CD has been approved by the EMA in 2022. Moreover, the Janus kinase-1 inhibitor upadacitinib has been available for the treatment of CD in the EU since 2023. For localized CD, elective surgical resection also remains a valid option with good long-term outcomes. Perianal and fistulizing CD are difficult to treat and require a close interdisciplinary collaboration between gastroenterologists and colorectal surgeons. Surgical fistula treatment with curative intent should only be performed in well-controlled CD. The recent increase in therapeutic options in CD is encouraging, since more safe and effective therapies are now available to patients. Nevertheless, CD remains an incurable disease and so far, for all existing treatments only a fraction of patients responds to the therapy. Therefore, the development of new therapies should continue.

Childlessness in Patients with Inflammatory Bowel Disease - Data from the Prospective Multi-center Swiss IBD Cohort Study.

BACKGROUND AND AIMS: Childlessness and infertility represent a frequent and important issue in inflammatory bowel disease (IBD) patients. Nevertheless, until now epidemiological data remains scarce. Therefore, main objectives of this study were to evaluate the rate of childlessness and the cumulative probability of reproduction in female and male IBD patients within the Swiss Inflammatory Bowel Disease Cohort Study (SIBDCS), a large prospective multicenter nationwide cohort. METHODS: Prospectively collected data of SIBDCS was used, comprising more than 3,300 patients with Crohn's disease (CD) and ulcerative colitis (UC). We analyzed the following groups of patients: 1) female IBD patients aged ≥40 years and diagnosed before age of 30 years with at least one follow-up, 2) female IBD patients who reported actively trying to conceive, with IBD diagnosed <35 years and with age at enrolment <45 years (longitudinal observation), with at least one follow-up, and 3) childless males who actively tried to conceive. RESULTS: A total of 1,412 female patients from the SIBDCS [843 CD, 539 UC, 30 indeterminate colitis (IC)] with available data were included in our analyses. Out of those 184 females (70.1% CD and 29.9 % UC) were aged ≥ 40 years and have been diagnosed with IBD before the age of 30 years. Among these, 184 women 32.1% were childless. The portion of childless females (36.4%) was significantly higher in CD vs. UC (36.4% vs. 21.8%; p=0.026), equaling a relative risk of childlessness of 1.7 in CD vs. UC. and higher than in the Swiss general population (21%). The mean number of children per female patient was 1.32 (median 1, min 0, max 6), per female with CD 1.12 (median 1, min 0, max 4), per female with UC/IC 1.78 (median 2, min 0, max 6; P=0.001). The longitudinal analysis of female IBD patients trying to conceive revealed that one out of two women neither were pregnant nor had born a child five years after first trying to conceive. CONCLUSIONS: The rate of childlessness in females with CD is higher compared to the general Swiss population, whereas it is similar in women with UC. Moreover, the mean number of children is lower in CD than in UC. Females with CD remain more often childless compared to their UC counterparts. Although the exact underlying mechanisms are largely unknown, this discrepancy should alert healthcare professionals treating CD patients to actively address this topic.

The Bern Birth Cohort (BeBiCo) to study the development of the infant intestinal microbiota in a high-resource setting in Switzerland: rationale, design, and methods.

BACKGROUND: Microbiota composition is fundamental to human health with the intestinal microbiota undergoing critical changes within the first two years of life. The developing intestinal microbiota is shaped by maternal seeding, breast milk and its complex constituents, other nutrients, and the environment. Understanding microbiota-dependent pathologies requires a profound understanding of the early development of the healthy infant microbiota. METHODS: Two hundred and fifty healthy pregnant women (≥20 weeks of gestation) from the greater Bern area will be enrolled at Bern University hospital's maternity department. Participants will be followed as mother-baby pairs at delivery, week(s) 1, 2, 6, 10, 14, 24, 36, 48, 96, and at years 5 and 10 after birth. Clinical parameters describing infant growth and development, morbidity, and allergic conditions as well as socio-economic, nutritional, and epidemiological data will be documented. Neuro-developmental outcomes and behavior will be assessed by child behavior checklists at and beyond 2 years of age. Maternal stool, milk, skin and vaginal swabs, infant stool, and skin swabs will be collected at enrolment and at follow-up visits. For the primary outcome, the trajectory of the infant intestinal microbiota will be characterized by 16S and metagenomic sequencing regarding composition, metabolic potential, and stability during the first 2 years of life. Secondary outcomes will assess the cellular and chemical composition of maternal milk, the impact of nutrition and environment on microbiota development, the maternal microbiome transfer at vaginal or caesarean birth and thereafter on the infant, and correlate parameters of microbiota and maternal milk on infant growth, development, health, and mental well-being. DISCUSSION: The Bern birth cohort study will provide a detailed description and normal ranges of the trajectory of microbiota maturation in a high-resource setting. These data will be compared to data from low-resource settings such as from the Zimbabwe-College of Health-Sciences-Birth-Cohort study. Prospective bio-sampling and data collection will allow studying the association of the microbiota with common childhood conditions concerning allergies, obesity, neuro-developmental outcomes , and behaviour. Trial registration The trial has been registered at www. CLINICALTRIALS: gov , Identifier: NCT04447742.

Because I'm happy - positive affect and its predictive value for future disease activity in patients with inflammatory bowel diseases: a retrospective cohort study.

Background: While the detrimental impact of negative emotions on the clinical course of inflammatory bowel disease (IBD) and quality of life has been extensively investigated, evidence for a potential impact of positive emotions is scarce. Objectives: We aim to analyse contributing factors of positive affect and their predictive value for disease course in IBD patients. Design: In this retrospective cohort study, epidemiological, psychosocial and IBD disease characteristics of Swiss IBD cohort study patients were analysed longitudinally. Methods: Epidemiological, psychosocial and disease characteristics were extracted from the database of the Swiss IBD cohort study. Participants' positive emotions were assessed cross-sectionally with the seven-item Marburg questionnaire (range 1-6) addressing positive affect in different aspects of daily life. Predictors of positive emotions were identified by linear regression. The quantitative longitudinal impact of positive emotions on the further disease course was analysed using a multivariable Cox proportional hazards model. Results: Among 702 IBD patients, those reporting more positive emotions were found to have significantly less intense medical treatment, less pain and fewer depressive symptoms (p < 0.05). A higher percentage of variability in positive emotions was explained by pain (36%) and depressive symptoms (13%) than by epidemiological characteristics (0.3%), or characteristics of IBD and its treatment (2.4%). Patients with higher levels of positive emotions (score > 3.5) experienced longer flare-free survival, also after adjusting for confounders (adjusted hazard ratio: 0.39, p < 0.05). Conclusions: The absence of pain and depressive symptoms were the strongest drivers for high positive affect. Higher scores of positive affect were associated with longer disease-free survival in IBD patients.

STAR SIGN study: Evaluation of COVID-19 vaccine efficacy against the SARS-CoV-2 variants BQ.1.1 and XBB.1.5 in patients with inflammatory bowel disease.

BACKGROUND: Vaccine-elicited immune responses are impaired in patients with inflammatory bowel disease (IBD) treated with anti-TNF biologics. AIMS: To assess vaccination efficacy against the novel omicron sublineages BQ.1.1 and XBB.1.5 in immunosuppressed patients with IBD. METHODS: This prospective multicentre case-control study included 98 biologic-treated patients with IBD and 48 healthy controls. Anti-spike IgG concentrations and surrogate neutralisation against SARS-CoV-2 wild-type, BA.1, BA.5, BQ.1.1, and XBB.1.5 were measured at two different time points (2-16 weeks and 22-40 weeks) following third dose vaccination. Surrogate neutralisation was based on antibody-mediated blockage of ACE2-spike protein-protein interaction. Primary outcome was surrogate neutralisation against tested SARS-CoV-2 sublineages. Secondary outcomes were proportions of participants with insufficient surrogate neutralisation, impact of breakthrough infection, and correlation of surrogate neutralisation with anti-spike IgG concentration. RESULTS: Surrogate neutralisation against all tested sublineages was reduced in patients with IBD who were treated with anti-TNF biologics compared to patients treated with non-anti-TNF biologics and healthy controls (each p ≤ 0.001) at visit 1. Anti-TNF therapy (odds ratio 0.29 [95% CI 0.19-0.46]) and time since vaccination (0.85 [0.72-1.00]) were associated with low, and mRNA-1273 vaccination (1.86 [1.12-3.08]) with high wild-type surrogate neutralisation in a ß-regression model. Accordingly, higher proportions of patients treated with anti-TNF biologics had insufficient surrogate neutralisation against omicron sublineages at visit 1 compared to patients treated with non-anti-TNF biologics and healthy controls (each p ≤ 0.015). Surrogate neutralisation against all tested sublineages decreased over time but was increased by breakthrough infection. Anti-spike IgG concentrations correlated with surrogate neutralisation. CONCLUSIONS: Patients with IBD who are treated with anti-TNF biologics show impaired neutralisation against novel omicron sublineages BQ.1.1 and XBB.1.5 and may benefit from prioritisation for future variant-adapted vaccines.

Benchmarking microbial DNA enrichment protocols from human intestinal biopsies.

Shotgun metagenomic sequencing is a powerful tool for studying bacterial communities in their natural habitats or sites of infection, without the need for cultivation. However, low microbial signals in metagenomic sequencing can be overwhelmed by host DNA contamination, resulting in decreased sensitivity for microbial read detection. Several commercial kits and other methods have been developed to enrich bacterial sequences; however, these assays have not been tested extensively for human intestinal tissues yet. Therefore, the objective of this study was to assess the effectiveness of various wet-lab and software-based approaches for depleting host DNA from microbiome samples. Four different microbiome DNA enrichment methods, namely the NEBNext Microbiome DNA Enrichment kit, Molzym Ultra-Deep Microbiome Prep, QIAamp DNA Microbiome kit, and Zymo HostZERO microbial DNA kit, were evaluated, along with a software-controlled adaptive sampling (AS) approach by Oxford Nanopore Technologies (ONT) providing microbial signal enrichment by aborting unwanted host DNA sequencing. The NEBNext and QIAamp kits proved to be effective in shotgun metagenomic sequencing studies, as they efficiently reduced host DNA contamination, resulting in 24% and 28% bacterial DNA sequences, respectively, compared to <1% in the AllPrep controls. Additional optimization steps using further detergents and bead-beating steps improved the efficacy of less efficient protocols but not of the QIAamp kit. In contrast, ONT AS increased the overall number of bacterial reads resulting in a better bacterial metagenomic assembly with more bacterial contigs with greater completeness compared to non-AS approaches. Additionally, AS also allowed for the recovery of antimicrobial resistance markers and the identification of plasmids, demonstrating the potential utility of AS for targeted sequencing of microbial signals in complex samples with high amounts of host DNA. However, ONT AS resulted in relevant shifts in the observed bacterial abundance, including 2 to 5 times more Escherichia coli reads. Furthermore, a modest enrichment of Bacteroides fragilis and Bacteroides thetaiotaomicron was also observed with AS. Overall, this study provides insight into the efficacy and limitations of various methods for reducing host DNA contamination in human intestinal samples to improve the utility of metagenomic sequencing.

Antenatal gut microbiome profiles and effect on pregnancy outcome in HIV infected and HIV uninfected women in a resource limited setting.

BACKGROUND: Human immunodeficiency virus (HIV) severely damages the epithelial cells of the gut lining leading to an inflamed leaky gut, translocation of microbial products, and dysbiosis resulting in systemic immune activation. Also, microbiota composition and maternal gut function can be altered in pregnancy through changes in the immune system and intestinal physiology. The aim of this study was to investigate the gut microbiota in HIV-infected and HIV-uninfected pregnant women and to compare and identify the association between gut microbial composition and adverse birth outcomes. RESULTS: A total of 94 pregnant women (35 HIV-infected and 59 HIV-uninfected controls) were recruited in Harare from 4 polyclinics serving populations with relatively poor socioeconomic status. Women were of a median age of 28 years (interquartile range, IQR: 22.3-32.0) and 55% of women were 35 weeks gestational age at enrolment (median 35.0 weeks, IQR: 32.5-37.2). Microbiota profiling in these participants showed that species richness was significantly lower in the HIV-infected pregnant women compared to their HIV-uninfected peers and significant differences in ß-diversity using Bray-Curtis dissimilarity were observed. In contrast, there was no significant difference in α-diversity between immune-compromised (CD4+ < 350 cells/µL) and immune-competent HIV-infected women (CD4+ ≥ 350 cells/µL) even after stratification by viral load suppression. HIV infection was significantly associated with a reduced abundance of Clostridium, Turicibacter, Ruminococcus, Parabacteroides, Bacteroides, Bifidobacterium, Treponema, Oscillospira, and Faecalibacterium and a higher abundance of Actinomyces, and Succinivibrio. Low infant birth weight (< 2500 g) was significantly associated with high abundances of the phylum Spirochaetes, the families Spirochaeteceae, Veillonellaceae, and the genus Treponema. CONCLUSION: The results reported here show that the species richness and taxonomy composition of the gut microbiota is altered in HIV-infected pregnant women, possibly reflecting intestinal dysbiosis. Some of these taxa were also associated with low infant birth weight.

Systemic and T cell-associated responses to SARS-CoV-2 immunisation in gut inflammation (STAR SIGN study): effects of biologics on vaccination efficacy of the third dose of mRNA vaccines against SARS-CoV-2.

BACKGROUND: Immunosuppressed patients with inflammatory bowel disease (IBD) experience increased risk of vaccine-preventable diseases such as COVID-19. AIMS: To assess humoral and cellular immune responses following SARS-CoV-2 booster vaccination in immunosuppressed IBD patients and healthy controls. METHODS: In this prospective, multicentre, case-control study, 139 IBD patients treated with biologics and 110 healthy controls were recruited. Serum anti-SARS-CoV-2 spike IgG concentrations were measured 2-16 weeks after receiving a third mRNA vaccine dose. The primary outcome was to determine if humoral immune responses towards booster vaccines differ in IBD patients under anti-TNF versus non-anti-TNF therapy and healthy controls. Secondary outcomes were antibody decline, impact of previous infection and SARS-CoV-2-targeted T cell responses. RESULTS: Anti-TNF-treated IBD patients showed reduced anti-spike IgG concentrations (geometric mean 2357.4 BAU/ml [geometric SD 3.3]) when compared to non-anti-TNF-treated patients (5935.7 BAU/ml [3.9]; p < 0.0001) and healthy controls (5481.7 BAU/ml [2.4]; p < 0.0001), respectively. In multivariable modelling, prior infection (geometric mean ratio 2.00 [95% CI 1.34-2.90]) and vaccination with mRNA-1273 (1.53 [1.01-2.27]) increased antibody concentrations, while anti-TNF treatment (0.39 [0.28-0.54]) and prolonged time between vaccination and antibody measurement (0.72 [0.58-0.90]) decreased anti-SARS-CoV-2 spike antibodies. Antibody decline was comparable in IBD patients independent of anti-TNF treatment and antibody concentrations could not predict breakthrough infections. Cellular and humoral immune responses were uncoupled, and more anti-TNF-treated patients than healthy controls developed inadequate T cell responses (15/73 [20.5%] vs 2/100 [2.0%]; p = 0.00031). CONCLUSIONS: Anti-TNF-treated IBD patients have impaired humoral and cellular immunogenicity following SARS-CoV-2 booster vaccination. Fourth dose administration may be beneficial for these patients.

Plasticity of the adult human small intestinal stoma microbiota.

The human distal small intestine (ileum) has a distinct microbiota, but human studies investigating its composition and function have been limited by the inaccessibility of the ileum without purging and/or deep intubation. We investigated inherent instability, temporal dynamics, and the contribution of fed and fasted states using stoma samples from cured colorectal cancer patients as a non-invasive access route to the otherwise inaccessible small and large intestines. Sequential sampling of the ileum before and after stoma formation indicated that ileostoma microbiotas represented that of the intact small intestine. Ileal and colonic stoma microbiotas were confirmed as distinct, and two types of instability in ileal host-microbial relationships were observed: inter-digestive purging followed by the rapid postprandial blooming of bacterial biomass and sub-strain appearance and disappearance within individual taxa after feeding. In contrast to the relative stability of colonic microbiota, the human small intestinal microbiota biomass and its sub-strain composition can be highly dynamic.

Challenges in the diagnosis of marginal zone lymphoma with symptoms of small intestinal disease: a case report and scoping review of the literature.

Background: Marginal zone lymphoma can be accompanied by symptoms of small intestinal disease including abdominal pain and malabsorption. However, the best diagnostic approach for suspected marginal zone lymphoma is unknown and intestinal biopsies are frequently negative. We describe the case of a patient with symptoms of small bowel involvement where marginal zone lymphoma could only be detected upon peripheral lymph node resection. To assess the clinical variability of intestinal marginal zone lymphoma as a rare clinical entity, a scoping review with systematic literature research was performed. Methods: A 57-year-old man presented with a 10-year history of postprandial abdominal pain, systemic inflammation and recent weight loss. Endoscopies and a surgical small bowel specimen revealed non-specific findings. Flow cytometry from the bone marrow was highly suspicious for marginal zone lymphoma. A 2-18F-fluorodeoxyglucose-positron emission tomography/computed tomography (2-18F-FDG-PET/CT) showed hypermetabolic lymph nodes on both sides of the diaphragm. Cervical lymph node dissection finally confirmed marginal zone lymphoma. Immunochemotherapy yielded lasting oncological remission and resolved symptoms. We searched PubMed, Embase and Ovid MEDLINE® for additional case reports limited to the last 25 years. Five primary search terms combined using "AND" were used freely and as controlled vocabulary. Additional studies were identified by reviewing the reference lists of included articles. Results: Our review revealed 52 cases of marginal zone lymphoma with small intestinal manifestation. Patients presented with abdominal pain, bowel obstruction, weight loss or gastrointestinal bleeding. Diagnosis was mainly established by surgery (73%). The most frequent endoscopic findings were mucosal erosions and ulcerations. A 2-18F-FDG-PET/CT was positive in 9/15 patients. Treatment included rituximab, chemotherapy, surgery and/or radiation resulting in clinical remission in 82% of cases. Conclusions: Diagnostic workup for suspected small intestinal marginal zone lymphoma is challenging, necessitating a multidisciplinary approach. Endoscopy, imaging including 2-18F-FDG-PET/CT and small bowel resection or dissection of hypermetabolic lymph nodes can be useful. If marginal zone lymphoma is suspected vigorous diagnostic efforts are justified since remission can be achieved in most patients. Our review highlights the variable clinical presentation of this underdiagnosed disease and adds systematic data to the literature.

Effect of closed and permanent stoma on disease course, psychological well-being and working capacity in Swiss IBD cohort study patients.

BACKGROUND: Little is known about the impact of ostomy formation in inflammatory bowel disease patients on course of disease, psychological well-being, quality of life and working capacity. METHODS: We analyzed patients over a follow-up of up to 16 years in the Swiss inflammatory bowel disease cohort study (SIBDCS) with prospective data collection. We compared Ulcerative colitis and Crohn's disease patients with and without ostomy as well as permanent and closed stoma formation before and after surgery, investigating disease activity, psychological wellbeing and working capacity in a case-control design. RESULTS: Of 3825 SIBDCS patients, 176 with ostomy were included in the study and matched with 176 patients without ostomy using propensity score, equaling 352 patients for the analysis. As expected, we observed a lower mean and maximal disease activity in patients after stoma surgery compared with control patients without stoma. Overall, psychological wellbeing in patients with stomas vs. controls as well as patients with permanent vs. closed stoma was similar in terms of disease-specific quality of life (total score of the Inflammatory Bowel Disease Quality of Life questionnaire), psychological distress (total score of the Hospital Anxiety and Depression Scale), and stress at work (effort-reward-imbalance ratio), with the exception of a higher Posttraumatic Diagnostic Scale total score in patient with vs. without stoma. Compared to IBD patients without stoma, the adverse impact on working capacity in overall stoma IBD patients appeared to be modest. However we observe a significantly higher reduction in working capacity in permanent vs. closed stoma in CD but not UC patients. CONCLUSION: As to be expected, IBD patients may benefit from closed and permanent stoma application. Stoma surgery appears to only modestly impact working capacity. Importantly, stoma surgery was not associated with adverse psychological outcomes, with comparable psychological well-being regardless of presence and type of stoma.

The personality traits activity, self-reproach, and negative affect jointly predict clinical recurrence, depressive symptoms, and low quality of life in inflammatory bowel disease patients.

BACKGROUND: The bidirectional "gut-brain axis" has been implicated in the pathogenesis of inflammatory bowel diseases (IBD). While the influence of stress and depressive symptoms on IBD is well-characterized, the role of personality remains insufficiently investigated. METHODS: Personality was assessed in 1154 Swiss IBD cohort study (SIBDCS) patients via the NEO-Five-Factor Inventory (NEO-FFI) as well as in 2600 participants of the population-based CoLaus¦PsyCoLaus cohort study (NEO-FFI-revised). The NEO-FFI subcomponents activity, self-reproach and negative affect were associated with higher IBD disease activity and were combined to a NEO-FFI risk score. This risk score was validated and its effect on clinical IBD course and psychological endpoints was analysed in time-to-event and cumulative incidence analyses. RESULTS: In time-to-event analyses, a high NEO-FFI risk score was predictive for the clinical endpoints of new extraintestinal manifestation [EIM, adjusted hazard ratio (aHR) = 1.64, corrected p value (q) = 0.036] and two established composite flare endpoints (aHR = 1.53-1.63, q = 0.003-0.006) as well as for the psychological endpoints depressive symptoms (aHR = 7.06, q < 0.001) and low quality of life (aHR = 3.06, q < 0.001). Furthermore, cumulative incidence analyses showed that patients at high NEO-FFI risk experienced significantly more episodes of active disease, new EIMs, one of the flare endpoints, depressive episodes and low disease-related quality of life. Personalities of IBD patients showed only minor differences from the general population sample (Pearson's r = 0.03-0.14). CONCLUSIONS: Personality assessed by the NEO-FFI contained considerable predictive power for disease recurrence, depressive symptoms and low quality of life in IBD patients. Nevertheless, the personalities of IBD patients did not substantially differ from the general population.

Effectiveness of golimumab in patients with ulcerative colitis: results of a real-life study in Switzerland.

BACKGROUND: Tumor necrosis factor (TNF) inhibitors have improved treatment of ulcerative colitis (UC), but loss of response remains a frequent problem. The anti-TNF agent, golimumab, was approved in Switzerland for the treatment of UC in 2014. This study aims to summarize the experience of golimumab in a real-world setting in Switzerland. METHODS: We analyzed real-world data from 1769 UC patients from the Swiss Inflammatory Bowel Disease Cohort (SIBDC) study and performed a chart review of golimumab-treated patients. We extracted the partial Mayo score at t0 (baseline), t1 (2-16 weeks), t2 (17-35 weeks), and t3 (36-89 weeks). The primary endpoint was clinical response at t1, defined as marked improvement in partial Mayo score and objective parameters. Clinical remission was defined as resolution of symptoms and normalization of objective parameters. RESULTS: Our chart review included 103 UC patients with golimumab treatment (5.8% of all SIBDC UC patients); only 16 (15.5%) were anti-TNF naïve. Sixty-three patients remained on golimumab (61.2%) after 180 days, 51 (44.7%) after 365 days, and 34 (33%) after 630 days after the start of treatment. Upon golimumab treatment, the partial Mayo score decreased from 4 [interquartile range (IQR): 2-6] at t0 to 2 (IQR: 0-4) at t1, 1 (IQR: 0-3.5) at t2, and 1 (IQR: 0-3) at t3 (p < 0.001 for all comparisons with t0). The primary endpoint, clinical response at t1, could be evaluated in 52 patients and was met in 15 individuals (28.8%). Clinical remission at t1 was observed in 8 out of 52 patients (15.4%). Golimumab was generally well tolerated, one patient developed meningitis. The most frequent reasons to stop treatment were primary and secondary non-response. CONCLUSION: Golimumab was used in 5.8% of Swiss UC patients, mainly in biologic-experienced individuals. Golimumab treatment was associated with a sustained reduction of symptoms and clinical response in approximately 30% of patients.[ClinicalTrials.gov identifier: NCT00488631].

Depressive Symptoms Predict Clinical Recurrence of Inflammatory Bowel Disease.

BACKGROUND: Inflammatory bowel disease (IBD) patients are at high risk for depression, and depression has been shown to affect disease course. We examined interrelations between depression, genetic risk factors for depression, and IBD flares. METHOD: In 1973 patients (1137 Crohn's disease, 836 ulcerative colitis) of the Swiss IBD Cohort Study (SIBDCS), depressive status (hospital anxiety and depression subscale for depression, HADS-D ≥11) was assessed on a yearly basis. We investigated the impact of depression on IBD-relevant clinical outcomes in Cox proportional hazards models. We used active disease (CDAI ≥150 or MTWAI ≥10) and 2 published composite flare definitions-FNCE (physician-reported flare, nonresponse to therapy, new complication, or extraintestinal manifestation) and AFFSST (active disease, physician-reported flare, fistula, stenosis, and new systemic therapy)-as clinical end points. Additionally, 62 preselected single nucleotide polymorphisms (SNPs) were screened for cross-sectional associations with depression, and if present, their predictive value for future depression and clinical deterioration was assessed. RESULTS: Depression was a strong risk factor for disease-related end points, including active disease (adjusted hazard ratio [aHR], 3.55; P < 0.001), AFFSST (aHR, 1.62; P < 0.001), and FNCE (aHR, 1.35; P = 0.019). The SNP rs2522833 was significantly associated with depression at enrollment (q = 0.059). The TC allele of rs588765 was negatively associated with the presence of depression at enrollment (q = 0.050) and after enrollment (aHR, 0.67; P = 0.035) and with fewer active disease states (aHR, 0.72; P = 0.045) during follow-up. CONCLUSION: In IBD, depressive symptoms and inflammatory activity are intimately related. Depressive symptoms were a strong predictor of clinical deterioration, and genetic markers may play a role in this relationship.

Association between proton-pump inhibitors and the risk of gastric cancer: a systematic review with meta-analysis.

INTRODUCTION: The use of proton-pump inhibitors (PPI) may be associated with an increased risk of gastric cancer (GC). OBJECTIVE: To review and meta-analyse available literature investigating the association between PPI use and GC risk. METHODS: Two independent reviewers systematically searched Ovid MEDLINE, EMBASE, and Cochrane Library (inception to July 2020) for case-control and cohort studies assessing the association between PPI use and GC according to a predefined protocol in PROSPERO (CRD42018102536). Reviewers independently assessed study quality, extracted data, and meta-analysed available and newly calculated odds ratios (ORs) using a random-effects model, and stratified for GC site (cardia versus non-cardia) and PPI duration (<1 year, 1-3 years, >3 years). RESULTS: We screened 2,396 records and included five retrospective cohort and eight case-control studies comprising 1,662,881 individuals in our meta-analysis. In random-effect models, we found an increased GC risk in PPI users [OR: 1.94, 95% confidence interval (95% CI): 1.47-2.56] with high statistical heterogeneity (I 2 = 82%) and overall moderate risk of bias. Stratified analyses indicated a significant risk increase in non-cardia (OR: 2.20, 95% CI: 1.44-3.36, I 2 = 77%) with a similar non-significant trend in cardia regions (OR: 1.77, 95% CI: 0.72-4.36, I 2 = 66%). There was no GC increase with longer durations of PPI exposure (<1 year: OR: 2.29, 95% CI: 2.13-2.47, I 2 = 0%; 1-3 years: OR: 1.46, 95% CI: 0.53-4.01, I 2 = 35%; >3 years: OR: 2.08, 95% CI: 0.56-7.77, I 2 = 61%). CONCLUSION: We found a twofold increased GC risk among PPI users, but this association does not confirm causation and studies are highly heterogeneous. PPI should only be prescribed when strictly indicated.