Patients with autoimmune liver disease have glucose disturbances that mechanistically differ from steatotic liver disease.

Autoimmune liver diseases are associated with an increased risk of diabetes, yet the underlying mechanisms remain unknown. In this cross-sectional study, we investigated the glucose-regulatory disturbances in patients with autoimmune hepatitis (AIH, n = 19), primary biliary cholangitis (PBC, n = 15), and primary sclerosing cholangitis (PSC, n = 6). Healthy individuals (n = 24) and patients with metabolic dysfunction-associated steatotic liver disease (MASLD, n = 18) were included as controls. Blood samples were collected during a 120-min oral glucose tolerance test. We measured the concentrations of glucose, C-peptide, insulin, glucagon, and the two incretin hormones, glucose insulinotropic peptide (GIP) and glucagon-like peptide-1 (GLP-1). We calculated the homeostasis model assessment of insulin resistance (HOMA-IR), whole body insulin resistance (Matsuda index), insulin clearance, and insulinogenic index. All patient groups had increased fasting plasma glucose and impaired glucose responses compared with healthy controls. Beta-cell secretion was increased in AIH, PBC, and MASLD but not in PSC. Patients with AIH and MASLD had hyperglucagonemia and hepatic, as well as peripheral, insulin resistance and decreased insulin clearance, resulting in hyperinsulinemia. Patients with autoimmune liver disease had an increased GIP response, and those with AIH or PBC had an increased GLP-1 response. Our data demonstrate that the mechanism underlying glucose disturbances in patients with autoimmune liver disease differs from that underlying MASLD, including compensatory incretin responses in patients with autoimmune liver disease. Our results suggest that glucose disturbances are present at an early stage of the disease.NEW & NOTEWORTHY Patients with autoimmune liver disease but without overt diabetes display glucose disturbances early on in their disease course. We identified pathophysiological traits specific to these patients including altered incretin responses.

Cancer in Patients With Familial Adenomatous Polyposis: A Nationwide Danish Cohort Study With Matched Controls.

BACKGROUND & AIMS: Familial adenomatous polyposis (FAP) is a hereditary disorder that predisposes patients to colorectal cancer (CRC). Prophylactic colectomy has greatly reduced the risk of CRC. However, new associations between FAP and the risk of other cancers have subsequently emerged. In this study, we assessed the risk of specific primary and secondary cancers among patients with FAP compared with matched controls. METHODS: All known patients with FAP up until April 2021 were identified in the nationwide Danish Polyposis Register and paired with 4 unique controls matched by birth year, sex, and postal code. The risk of overall cancers, specific cancer types, and risk of a second primary cancer was assessed and compared with controls. RESULTS: The analysis included 565 patients with FAP and 1890 controls. The overall risk of cancer was significantly higher for patients with FAP than for controls (hazard ratio [HR], 4.12; 95% confidence interval [CI], 3.28-5.17; P < .001). The increased risk was mainly due to CRC (HR, 4.61; 95% CI, 2.58-8.22; P < .001), pancreatic cancer (HR, 6.45; 95% CI, 2.02-20.64; P = .002), and duodenal/small-bowel cancer (HR, 14.49; 95% CI, 1.76-119.47; P = .013), whereas no significant difference was observed for gastric cancer (HR, 3.29; 95% CI, 0.53-20.23; P = .20). Furthermore, the risk of a second primary cancer was significantly higher for patients with FAP (HR, 1.89; 95% CI, 1.02-3.50; P = .042). Between 1980 and 2020, the risk of cancer among patients with FAP decreased by ∼50%. CONCLUSIONS: Despite an absolute reduction in the risk of developing cancer among patients with FAP, the risk remained significantly higher than for the background population due to colorectal, pancreatic, and duodenal/small-bowel cancers.

Psychiatric and Educational Aspects of Familial Adenomatous Polyposis: A Nationwide Danish Cohort Study With Matched Nonexposed Individuals.

INTRODUCTION: Familial adenomatous polyposis (FAP) is an autosomal, dominantly inherited disorder that predisposes to colorectal cancer. An increased risk of cancer may affect mental health, but the magnitude of this effect remains unknown. We assessed the psychosocial functioning, including the educational level attained and risk of psychiatric comorbidity, of patients with FAP by comparing them with matched nonexposed individuals. METHODS: All Danish patients with FAP diagnosed before April 2021 were identified in the Danish Polyposis Register and paired with 4 matched nonexposed individuals. Educational history, psychiatric contacts or diagnoses ( International Classification of Disease, 10th Revision ), and treatment with antidepressants, anxiolytics, or antipsychotics were compared between patients with FAP and nonexposed individuals. RESULTS: The analysis included 445 patients with FAP and 1,538 nonexposed individuals. The highest educational level reached was significantly lower for patients with FAP ( P < 0.001). When comparing patients with FAP and nonexposed and adjusting for a cancer diagnosis, an increased risk was observed for a psychiatric contact (1.69, 95% confidence interval [CI] 1.25-2.29, P < 0.001), any psychiatric prescription (1.39, 95% CI 1.17-1.66, P < 0.001), a psychiatric diagnosis (1.64, 95% CI 1.19-2.26, P = 0.002), and experiencing any psychiatric event (hazard ratio 1.42, 95% CI 1.20-1.68, P < 0.001). An increased risk was specifically seen for mood (affective) disorders (1.76, 95% CI 1.09-2.83, P = 0.02) and behavioral and emotional disorders (2.01, 95% CI 1.10-3.69, P = 0.02) and the need for antidepressants (1.59, 95% CI 1.24-2.03, P < 0.001) and antipsychotics (1.85, 95% CI 1.26-2.70, P = 0.002). DISCUSSION: Compared with nonexposed individuals, patients with had significantly less education and an increased risk of developing mood and behavioral disorders, with an increased likelihood of needing antidepressants and antipsychotics.

Risk of malignancy in a high-incidence population-based cohort of Faroese patients with inflammatory bowel disease from 1960 to 2020 - a Faroese IBD cohort study.

BACKGROUND: The association between inflammatory bowel disease (IBD) and malignancy remains disputed despite many observational studies. The Faroese population exhibits the highest occurrence of IBD in the world. This study aimed to investigate the cancer risk in Faroese IBD patients in a nationwide IBD cohort. METHODS: This study included all IBD patients diagnosed in the Faroe Islands between 1960 and 2020. Clinical demographics and cancer diagnoses were retrieved from patient files and the Faroese cancer registry. Cancer risk in IBD patients was calculated as standardized incidence ratios (SIRs) based on the Faroese background population's age- and sex-specific cancer incidence rates, retrievable from NORDCAN. RESULTS: The cohort consisted of 699 patients with a total follow-up time of 9,629 person-years. Overall, the risk of cancer was not statistically significantly increased compared to the background population. Patients diagnosed with cancer at age 50-59 years had higher overall cancer risk (SIR 1.8; 95% CI, 1.02-2.99) as did UC patients diagnosed with IBD at 50-59 (SIR 2.1; 95% CI, 1.10-3.54). Absolute numbers were small and no estimates for site-specific cancers reached statistical significance, though lung, breast, and cancer of the female reproductive organs were elevated among IBD and UC patients, and colorectal cancer in CD patients. CONCLUSIONS: This nationwide study found no statistically significantly increased risk of cancer among Faroese patients with CD or UC, except from age 50 to 59 years. While the incidence of IBD is significantly higher in the Faroe Islands than in other countries, risk estimates of cancers are comparable.

Point-of-Care Testing and Home Testing: Pragmatic Considerations for Widespread Incorporation of Stool Tests, Serum Tests, and Intestinal Ultrasound.

Breaking through the biologic therapy efficacy plateau for inflammatory bowel disease requires the strategic development of personalized biomarkers in the tight control model. After risk stratification early in the disease course, targeted serial monitoring consistently to assess clinical outcomes in response to therapy allows for quick therapeutic adjustments before bowel damage can occur. Point-of-care intestinal ultrasound performed by the treating gastroenterologist is an accurate cross- sectional biomarker that monitors intestinal inflammation in real-time, enhances patient care, and increases shared understanding to help achieve common treatment goals. Combining intestinal ultrasound during a clinic visit with existing serum and stool biomarkers in a home testing setup with electronic health monitoring allows for an optimized, patient-centered personalized treatment algorithm that may improve treatment outcomes. Here, we review the current state, pragmatic considerations, and future implications of point-of-care testing and home testing for noninvasive inflammatory bowel disease monitoring in the tight control model.

I-CARE, a European Prospective Cohort Study Assessing Safety and Effectiveness of Biologics in Inflammatory Bowel Disease.

BACKGROUND AND AIMS: There is a need to evaluate the benefit-risk ratio of current therapies in inflammatory bowel disease (IBD) patients to provide the best quality of care. The primary objective of I-CARE (IBD Cancer and serious infections in Europe) was to assess prospectively safety concerns in IBD, with specific focus on the risk of cancer/lymphoma and serious infections in patients treated with anti-tumor necrosis factor and other biologic monotherapy as well as in combination with immunomodulators. METHODS: I-CARE was designed as a European prospective longitudinal observational multicenter cohort study to include patients with a diagnosis of Crohn's disease, ulcerative colitis, or IBD unclassified established at least 3 months prior to enrollment. RESULTS: A total of 10,206 patients were enrolled between March 2016 and April 2019, including 6169 (60.4%) patients with Crohn's disease, 3853 (37.8%) with ulcerative colitis, and 184 (1.8%) with a diagnosis of IBD unclassified. Thirty-two percent of patients were receiving azathioprine/thiopurines, 4.6% 6-mercaptopurine, and 3.2% methotrexate at study entry. At inclusion, 47.3% of patients were treated with an anti-tumor necrosis factor agent, 8.8% with vedolizumab, and 3.4% with ustekinumab. Roughly one-quarter of patients (26.8%) underwent prior IBD-related surgery. Sixty-six percent of patients had been previously treated with systemic steroids. Three percent of patients had a medical history of cancer prior to inclusion and 1.1% had a history of colonic, esophageal, or uterine cervix high-grade dysplasia. CONCLUSIONS: I-CARE is an ongoing investigator-initiated observational European prospective cohort study that will provide unique information on the long-term benefits and risks of biological therapies in IBD patients. (EudraCT, Number: 2014-004728-23; ClinicalTrials.gov, Number: NCT02377258).

Autoimmune liver diseases and diabetes: A propensity score matched analysis and a proportional meta-analysis.

BACKGROUND AND AIMS: Patients with some chronic liver diseases have increased risk of diabetes. Whether this is also the case for patients with autoimmune liver diseases is unknown. The study aimed to calculate risk and worldwide prevalence of diabetes in patients with autoimmune hepatitis (AIH), primary biliary cholangitis (PBC) and primary sclerosing cholangitis (PSC). METHODS: We performed a case-control study using data from the United Kingdom Biobank (UKB) and compared frequency of type 1 diabetes (T1D) and type 2 diabetes (T2D) in AIH and PBC with age-, sex-, BMI- and ethnicity-matched controls. Next, we performed a systematic review and proportional meta-analysis searching PubMed, Embase, Cochrane Library and Web of Science (inception to 1 May 2022 [AIH]; 20 August 2022 [PBC]; 11 November 2022 [PSC]). The pooled prevalence of diabetes was calculated using an inverse method random effects model. RESULTS: Three hundred twenty-eight AIH patients and 345 PBC patients were identified in UKB and risk of T1D and T2D significantly increased compared with matched controls. Our systematic search identified 6914 records including the UKB study. Of these, 77 studies were eligible for inclusion comprising 36 467, 39 924 and 4877 individuals with AIH, PBC and PSC, respectively. The pooled prevalence of T1D was 3.8% (2.6%-5.7%), 1.7% (0.9%-3.1%), 3.1% (1.9%-4.8%) and of T2D 14.8% (11.1%-19.5%), 18.1% (14.6%-22.2%), 6.3% (2.8%-13.3%) in patients with AIH, PBC and PSC, respectively. CONCLUSIONS: Patients with autoimmune liver diseases have increased risk of diabetes. Increased awareness of diabetes risk in patients with autoimmune liver diseases is warranted.

Drug utilization of biologic therapy in Crohn's disease and ulcerative colitis: a population-based Danish cohort study 2015-2020.

OBJECTIVE: The aim of the study was to characterize the drug utilization and switch patterns of biological treatment of ulcerative colitis (UC) and Crohn's disease (CD). METHODS: Using Danish national registries, this nationwide study included individuals diagnosed with UC or CD, bio-naïve at the initiation of treatment with infliximab, adalimumab, vedolizumab, golimumab, or ustekinumab in 2015-2020. Hazard ratios of discontinuing the first treatment or switching to another biological treatment were explored using Cox regression. RESULTS: Among 2995 UC patients and 3028 CD patients, infliximab was used as a first-line biologic treatment in 89% of UC patients and 85% of CD patients, followed by adalimumab with 6%, vedolizumab with 3%, and golimumab with 1% for UC, and adalimumab with 12%, vedolizumab with 2%, and ustekinumab with 0.4% for CD.When comparing adalimumab as the first treatment series to infliximab, there was a higher risk of treatment discontinuation (excluding switch) among UC patients (hazard ratio: 2.02 [95% confidence interval: 1.57; 2.60]) and CD patients (1.85 [1.52; 2.24]). When comparing vedolizumab to infliximab, there was a lower risk of discontinuation for UC patients (0.51 [0.29-0.89]), and for CD patients, although not significantly (0.58 [0.32-1.03]). We observed no significant difference in the risk of switching to another biologic treatment for any of the biologics. CONCLUSION: More than 85% of UC and CD patients initiating biologic therapy had infliximab as their first-line biologic treatment, in accordance with official treatment guidelines. Future studies should explore the higher incidence of treatment discontinuation of adalimumab as the first treatment series.Key summarySeveral biologic therapies are available in the treatment of ulcerative colitis and Crohn's disease.Clinical guidelines stipulate that infliximab should be the first-line biologic therapy.Drug utilization studies comparing biologic therapies head-to-head are sparse.In Denmark, during 2015-2020 infliximab remained the most widely used biologic treatment, with adalimumab being second.One in four patients experienced more than one biologic during the study period.The risk of discontinuation of biologic treatment (and not starting a new biologic) was higher for initiators of adalimumab.Clinical and social background factors available from the registers could not account for the observed risk difference in discontinuation.

Health-related quality of life aspects of the 'Periodontitis prevalence in ulcerative colitis and Crohn's disease' (PPCC) cohort.

AIM: To assess whether oral health problems affect disease-specific quality of life (QoL) of inflammatory bowel disease (IBD) patients, and vice versa, whether IBD affects oral-health-related QoL. MATERIALS AND METHODS: Individuals reporting IBD and matched controls were surveyed on general anamnestic information, oral-health-related questions and the Oral Health Impact Profile (OHIP)-5. IBD patients were additionally surveyed on years since diagnosis, disease activity and severity as well as health-related QoL (Short Inflammatory Bowel Disease Questionnaire, sIBDQ). OHIP-5 and sIBDQ were defined as primary outcome parameters, and several predictors and confounders were used in adjusted univariable and multivariable regression analyses. RESULTS: Answers from 1108 IBD patients and 3429 controls were analysed. Compared with controls, IBD patients reported significantly more frequently an oral impact on daily life and worse oral-health-related QoL, with Crohn's disease (CD) patients being more severely affected than ulcerative colitis (UC) patients. The diagnosis of UC and CD, having <20 teeth, severe periodontitis and stressful daily-life experience were associated with a higher prevalence of poor oral-health-related QoL. Among IBD patients, an impaired IBD-specific, health-related QoL was significantly associated with the diagnosis of CD and depression, IBD activity and severity, having <20 teeth, presence of oral lesions and stressful daily-life experience, while a longer time since diagnosis was significantly associated with an improved IBD-specific, health-related QoL. CONCLUSIONS: The results of the present study indicate, for the first time, that oral health problems are associated with an impairment of IBD-specific health-related QoL, and vice versa, IBD is associated with an impaired oral health-related QoL. This emphasizes the potential advantages of including dental professionals in the multi-disciplinary treatment teams of IBD patients.

Exploring the Impact of Covid-19-Related Perceptions on Psychological Distress and Quality of Life in an International Gastrointestinal Cohort Over Time Guided by the Common Sense Model.

The aim of this longitudinal study was to examine changes in COVID-19 and illness-related perceptions, gastrointestinal symptoms, coping, catastrophising, psychological distress, and QoL during the COVID-19 pandemic. A total of 831 adults with a gastrointestinal condition completed an online questionnaire at baseline (May-October 2020). Of those, 270 (32.5%) participants (85.2% female, mean age = 47.3 years) provided follow-up data (March-May 2021). Repeated-measures multiple analysis of variance and a cross-lagged panel model were used to test the study hypotheses. Gastrointestinal symptoms and COVID-19 perceptions at follow-up were strongly predicted by their baseline values, while illness perceptions were predicted by baseline gastrointestinal symptoms. Cross-lagged relationships indicated a reciprocal relationship between gastrointestinal symptoms and psychological distress. Moreover, gastrointestinal symptoms had substantial predictive utility, strongly predicting future gastrointestinal symptoms, and to a lesser extent, more negative illness perceptions, greater psychological distress, and greater use of adaptive coping strategies across time.

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

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.

High Accuracy in Classifying Endoscopic Severity in Ulcerative Colitis Using Convolutional Neural Network.

INTRODUCTION: The evaluation of endoscopic disease severity is a crucial component in managing patients with ulcerative colitis (UC). However, endoscopic assessment suffers from substantial intraobserver and interobserver variations, limiting the reliability of individual assessments. Therefore, we aimed to develop a deep learning model capable of distinguishing active from healed mucosa and differentiating between different endoscopic disease severity degrees. METHODS: One thousand four hundred eighty-four unique endoscopic images from 467 patients were extracted for classification. Two experts classified all images independently of one another according to the Mayo endoscopic subscore (MES). In cases of disagreement, a third expert classified the images. Different convolutional neural networks were considered for automatically classifying UC severity. Five-fold cross-validation was used to develop and select the final model. Afterward, unseen test data sets were used for model evaluation. RESULTS: In the most challenging task-distinguishing between all categories of MES-our final model achieved a test accuracy of 0.84. When evaluating this model on the binary tasks of distinguishing MES 0 vs 1-3 and 0-1 vs 2-3, it achieved accuracies of 0.94 and 0.93 and areas under the receiver operating characteristic curves of 0.997 and 0.998, respectively. DISCUSSION: We have developed a highly accurate, new, automated way of evaluating endoscopic images from patients with UC. We have demonstrated how our deep learning model is capable of distinguishing between all 4 MES levels of activity. This new automated approach may optimize and standardize the evaluation of disease severity measured by the MES across centers no matter the level of medical expertise.

Validation of the Endoscopic Part of the Spigelman Classification for Evaluating Duodenal Adenomatosis in Familial Adenomatous Polyposis: A Prospective Study of Interrater and Intrarater Reliability.

INTRODUCTION: In patients with familial adenomatous polyposis, the Spigelman classification is recommended for staging and risk stratification of duodenal adenomatosis. Although the classification has been used for decades, it has never been formally validated. METHODS: We included consecutive FAP patients undergoing upper gastrointestinal endoscopic surveillance and evaluated the inter- and intrarater reliability of the Spigelman classification. RESULTS: The interrater reliability of the endoscopic parameters and the Spigelman classification was good and excellent, respectively. The intrarater reliability of the endoscopic parameters and the Spigelman classification was moderate and good, respectively. DISCUSSION: The results support continued use of the Spigelman classification as the primary end point for future studies and as key endoscopic performance measure.

The Global Incidence of Peptic Ulcer Disease Is Decreasing Since the Turn of the 21st Century: A Study of the Organisation for Economic Co-Operation and Development (OECD).

INTRODUCTION: Peptic ulcer disease (PUD) is a common cause of hospitalization worldwide. We assessed temporal trends in hospitalization for PUD in 36 Organisation for Economic Co-operation and Development (OECD) countries since the turn of the 21st century. METHODS: The OECD database contains data on PUD-related hospital discharges and mortality for 36 countries between 2000 and 2019. Hospitalization rates for PUD were expressed as annual rates per 100,000 persons. Joinpoint regression models were used to calculate the average annual percent change (AAPC) with 95% confidence intervals (CIs) for each country, which were pooled using meta-analyses. The incidence of PUD was forecasted to 2021 using autoregressive integrated moving average and Poisson regression models. RESULTS: The overall median hospitalization rate was 42.4 with an interquartile range of 29.7-60.6 per 100,000 person-years. On average, hospitalization rates (AAPC = -3.9%; 95% CI: -4.4, -3.3) and morality rates (AAPC = -4.7%; 95% CI: -5.6, -3.8) for PUD have decreased from 2000 to 2019 globally. The forecasted incidence of PUD hospitalizations in 2021 ranged from 3.5 per 100,000 in Mexico to 92.1 per 100,000 in Lithuania. Across 36 countries in the OECD, 329,000 people are estimated to be hospitalized for PUD in 2021. DISCUSSION: PUD remains an important cause of hospitalization worldwide. Reassuringly, hospitalizations and mortality for PUD have consistently been falling in OECD countries in North America, Latin America, Europe, Asia, and Oceania. Identifying underlying factors driving these trends is essential to sustaining this downward momentum.

Periodontitis prevalence in patients with ulcerative colitis and Crohn's disease - PPCC: A case-control study.

AIM: The aim of this questionnaire-based case-control study was to assess whether self-reported oral health and periodontitis in patients with ulcerative colitis (UC) and Crohn's disease (CD) differ from those in matched controls without inflammatory bowel disease (IBD). MATERIALS AND METHODS: A survey including questions on general anamnestic information, IBD diagnosis, and oral health was distributed online. Self-perceived overall health of teeth and gums, severe periodontitis, and tooth loss were defined as outcome parameters. RESULTS: Analyses were based on answers from 1108 patients with IBD and 3429 controls. Patients with IBD reported significantly worse oral health and more periodontal problems compared to controls. Regression analyses corrected for relevant confounders showed significantly increased odds for fair or poor self-perceived overall health of teeth and gums (odds ratio [OR] 2.147 and 2.736, respectively) and for severe periodontitis (OR 1.739 and 2.574, respectively) for patients with UC and CD compared to controls; patients with CD presented additionally 91% higher odds for having <20 remaining teeth. CONCLUSION: Patients with UC and CD have significantly increased odds for worse self-perceived oral health and severe periodontitis compared to controls, with the former being more severely affected and losing more teeth. It is strongly recommended that patients with IBD are kept under close surveillance to prevent periodontitis development and/or mitigate its progression.

Extending the Common Sense Model to Explore the Impact of the Fear of COVID-19 on Quality of Life in an International Inflammatory Bowel Disease Cohort.

The aim of this cross-sectional study was to use an extended common sense model (CSM) to evaluate the impact of fear of COVID-19 on quality of life (QoL) in an international inflammatory bowel disease cohort. An online study involving 319 adults (75% female, mean (SD) 14.06 (15.57) years of symptoms) completed the Gastrointestinal Symptom Rating Scale, Brief Illness Perceptions Questionnaire, Fear of Contracting COVID-19 Scale, Brief-COPE, Depression, Anxiety and Stress Scale, and the EUROHIS-QOL. The extended CSM had an excellent fit (χ2 (9) = 17.06, p = .05, χ2/N = 1.90, RMSEA = 0.05, SRMR = 0.04, CFI = .99, TLI = .97, GFI = 0.99), indicating the influence of gastrointestinal symptoms on QoL was mediated by illness perceptions, fear of COVID-19, adaptive and maladaptive coping, and psychological distress. Interventions targeting the fear of COVID-19 in the context of an individual's perceptions will likely enhance QoL during the pandemic.

Exploring the Relationship Between Self-Isolation and Distress Among People with Gastrointestinal Disorders During the COVID-19 Pandemic.

This study aimed to explore the association between perceived isolation and symptoms of distress in people with GI disorders at the time of the pandemic; and to examine factors which moderate this relationship. This online cross-sectional survey was advertised in May-September 2020 via patient organisations and associated social media. Overall, 831 people (82% female, mean age 49 years) from 27 countries participated. A significant relationship between social isolation and psychological distress was noted (r = .525, p < .001). GI symptoms moderated the association between isolation and distress (B = .047, t = 2.47, p = .015). Interventions targeting these factors may help to reduce distress in people with GI disorders at the time of major stressors such as the COVID-19 pandemic.

The Risk of Extraintestinal Cancer in Inflammatory Bowel Disease: A Systematic Review and Meta-analysis of Population-based Cohort Studies.

BACKGROUND & AIMS: Patients with Crohn's disease (CD) and ulcerative colitis (UC) are at increased risk of developing intestinal cancer. However, less is known about the risk of extraintestinal cancers (EICs). The aim of this study was to conduct a systematic review and meta-analysis of population-based cohorts assessing the risk of EICs in inflammatory bowel disease (IBD) patients. METHODS: Only population-based studies reporting on the prevalence or incidence of EICs were included. In total, 884 studies were screened and those included were assessed for quality. Eligible studies were pooled for length of follow-up evaluation, events in the IBD population, and events or expected events in a control population for the meta-analyses. RESULTS: In total, 40 studies were included in the systematic review and 15 studies were included in the meta-analysis. The overall risk of EICs was found to be increased in both CD (incidence rate ratio [IRR]: 1.43 [CI, 1.26, 1.63]) and UC (IRR: 1.15 [1.02, 1.31]) patients. Both CD and UC patients presented with an increased risk of skin (IRR: CD, 2.22 [1.41-3.48]; UC, 1.38 [1.12-1.71]) and hepatobiliary (IRR: CD, 2.31 [1.25-4.28]; UC, 2.05 [1.52-2.76]) malignancies. Furthermore, CD patients showed an increased risk of hematologic (IRR, 2.40 [1.81-3.18]) and lung (IRR, 1.53 [1.23-1.91]) cancers. These increased risks were present despite treatment with immunosuppressives. CONCLUSIONS: This systematic review and meta-analysis shows that both CD and UC patients are at an increased risk of developing EICs, both overall and at specific sites. However, additional studies with longer follow-up evaluation are needed to assess the true risk of EICs posed by IBD.

Coronavirus disease 2019, immune-mediated inflammatory diseases and immunosuppressive therapies - A Danish population-based cohort study.

BACKGROUND: Limited data exist regarding the disease course of coronavirus disease 2019 (COVID-19) and its relationship with immunosuppressants among patients with immune-mediated inflammatory diseases (IMIDs). Therefore, this study aims to investigate the association between COVID-19, frequent rheumatological, dermatological, gastrointestinal, and neurological IMIDs and immunosuppressants. METHODS: We conducted a Danish population-based cohort study including all residents living within Capital Region of Denmark and Region Zealand from January 28th, 2020 until September 15th, 2020 with the only eligibility criterion being a test for SARS-CoV-2 via reverse transcription-polymerase chain-reaction. Main outcomes included development of COVID-19, COVID-19-related hospitalization and mortality. RESULTS: COVID-19 was less common among patients with IMIDs than the background population (n = 328/20,513 (1.60%) and n = 10,792/583,788(1.85%), p < 0.01, respectively). However, those with IMIDs had a significantly higher risk of COVID-19-related hospitalization (31.1% and 18.6%, p < 0.01, respectively) and mortality (9.8% and 4.3%, p < 0.01, respectively), which were associated with patients older than 65 years, and presence of comorbidities. Furthermore, systemic steroids were independently associated with a severe course of COVID-19 (Odds ratio (OR) = 3.56 (95%CI 1.83-7.10), p < 0.01), while biologic therapies were associated with a reduced risk hereof (OR = 0.47 (95%CI 0.22-0.95), p = 0.04). Patients suspending immunosuppressants due to COVID-19 had an increased risk of subsequent hospitalization (OR = 3.59 (95%CI 1.31-10.78), p = 0.02). CONCLUSION: This study found a lower occurrence, but a more severe disease course, of COVID-19 among patients with IMIDs, which was associated with the use of systemic steroids for IMIDs and suspension of other immunosuppressants. This study emphasizes the importance of weighing risks before suspending immunosuppressants during COVID-19.

A Danish population-based case series of patients with liver cirrhosis and coronavirus disease 2019.

OBJECTIVES: Coronavirus disease 2019 (COVID-19) is an ongoing major health emergency, but its occurrence and clinical impact on patients withliver cirrhosis is unknown. Therefore, we conducted a population-based study of 2.6 million Danish citizens investigating the occurrence and impact of COVID-19 in patients with liver cirrhosis. MATERIALS AND METHODS: A prospective population-based cohort study was conducted in the Capital Region of Denmark and Region Zealand in the study period between 1 March 2020 up until 31 May 2020, with the only eligibility criteria being a reverse-transcriptase polymerase chain reaction for presence of viral genomic material confirming COVID-19. The patients were subsequently stratified according to presence of pre-existing liver cirrhosis. RESULTS: Among 575,935 individuals tested, 1713 patients had a diagnosis of cirrhosis. COVID-19 occurredsignificantly lessamongpatients with cirrhosis (n = 15; 0.9%, p < .01) compared with the population without cirrhosis (n = 10,593; 1.8%). However, a large proportion (n = 6;40.0%) required a COVID-19 related hospitalization which was correlated with higher values of alanine aminotransferase (p < .01) and lactate dehydrogenase (p = .04). In addition, one-in-three (n = 2; 13.3%) required intensive therapy. Four patients died (26.7%) and mortality was associated with higher MELD scores, co-existing type 2 diabetes, and bacterial superinfections. CONCLUSION: In conclusion, patientswith cirrhosis may have a lower risk of COVID-19; but a higher risk of complications hereto and mortality.