Morphologic and molecular analysis of liver injury after SARS-CoV-2 vaccination reveals distinct characteristics.

BACKGROUND & AIMS: Liver injury after COVID-19 vaccination is very rare and shows clinical and histomorphological similarities with autoimmune hepatitis (AIH). Little is known about the pathophysiology of COVID-19 vaccine-induced liver injury (VILI) and its relationship to AIH. Therefore, we compared VILI with AIH. METHODS: Formalin-fixed and paraffin-embedded liver biopsy samples from patients with VILI (n = 6) and from patients with an initial diagnosis of AIH (n = 9) were included. Both cohorts were compared by histomorphological evaluation, whole-transcriptome and spatial transcriptome sequencing, multiplex immunofluorescence, and immune repertoire sequencing. RESULTS: Histomorphology was similar in both cohorts but showed more pronounced centrilobular necrosis in VILI. Gene expression profiling showed that mitochondrial metabolism and oxidative stress-related pathways were more and interferon response pathways were less enriched in VILI. Multiplex analysis revealed that inflammation in VILI was dominated by CD8+ effector T cells, similar to drug-induced autoimmune-like hepatitis. In contrast, AIH showed a dominance of CD4+ effector T cells and CD79a+ B and plasma cells. T-cell receptor (TCR) and B-cell receptor sequencing showed that T and B cell clones were more dominant in VILI than in AIH. In addition, many T cell clones detected in the liver were also found in the blood. Interestingly, analysis of TCR beta chain and Ig heavy chain variable-joining gene usage further showed that TRBV6-1, TRBV5-1, TRBV7-6, and IgHV1-24 genes are used differently in VILI than in AIH. CONCLUSIONS: Our analyses support that SARS-CoV-2 VILI is related to AIH but also shows distinct differences from AIH in histomorphology, pathway activation, cellular immune infiltrates, and TCR usage. Therefore, VILI may be a separate entity, which is distinct from AIH and more closely related to drug-induced autoimmune-like hepatitis. IMPACT AND IMPLICATIONS: Little is known about the pathophysiology of COVID-19 vaccine-induced liver injury (VILI). Our analysis shows that COVID-19 VILI shares some similarities with autoimmune hepatitis, but also has distinct differences such as increased activation of metabolic pathways, a more prominent CD8+ T cell infiltrate, and an oligoclonal T and B cell response. Our findings suggest that VILI is a distinct disease entity. Therefore, there is a good chance that many patients with COVID-19 VILI will recover completely and will not develop long-term autoimmune hepatitis.

Hierarchical contribution of individual lifestyle factors and their interactions on adenomatous and serrated polyp risk.

BACKGROUND: Individual colorectal polyp risk factors are well characterized; however, insights into their pathway-specific interactions are scarce. We aimed to identify the impact of individual risk factors and their joint effects on adenomatous (AP) and serrated polyp (SP) risk. METHODS: We collected information on 363 lifestyle and metabolic parameters from 1597 colonoscopy participants, resulting in over 521,000 data points. We used multivariate statistics and machine-learning approaches to assess associations of single variables and their interactions with AP and SP risk. RESULTS: Individual factors and their interactions showed common and polyp subtype-specific effects. Abdominal obesity, high body mass index (BMI), metabolic syndrome, and red meat consumption globally increased polyp risk. Age, gender, and western diet associated with AP risk, while smoking was associated with SP risk. CRC family history was associated with advanced adenomas and diabetes with sessile serrated lesions. Regarding lifestyle factor interactions, no lifestyle or dietary adjustments mitigated the adverse smoking effect on SP risk, whereas its negative effect was exacerbated by alcohol in the conventional pathway. The adverse effect of red meat on SP risk was not ameliorated by any factor, but was further exacerbated by western diet along the conventional pathway. No modification of any factor reduced the negative impact of metabolic syndrome on AP risk, whereas increased fatless fish or meat substitutes' intake mitigated its effect on SP risk. CONCLUSIONS: Individual risk factors and their interactions for polyp formation along the adenomatous and serrated pathways are strongly heterogeneous. Our findings may facilitate tailored lifestyle recommendations and contribute to a better understanding of how risk factor combinations impact colorectal carcinogenesis.

Therapies in Inflammatory Bowel Disease Patients with Extraintestinal Manifestations.

Extraintestinal manifestations (EIM) have become an important source of morbidity and disability as well as an identified risk factor for an unfavorably course of disease in inflammatory bowel diseases (IBD). Therefore, efforts have been put into a more global and interdisciplinary management of IBD patients in collaboration with rheumatologists, dermatologists, and ophthalmologists. A real therapeutic success has also been obtained with a more "systemic" IBD treatment associated with the development of monoclonal antibodies against TNF alpha and biological agents derived from the treatment of rheumatological disease (also called biological Disease-Modifying Antirheumatic Drugs). The prevalence of these EIM remains too low to undergo randomized controlled trials with this specific focus and therefore the evidence relies on case series and experts' opinions, which lowers the level of evidence. After a careful review of the most recent literature, this paper aims to update the reader on the latest therapeutic management of IBD patients with EIM.

Treatment Algorithm for Mild and Moderate-to-Severe Ulcerative Colitis: An Update.

BACKGROUND: Patient care in ulcerative colitis (UC) remains challenging despite an array of established treatment options and emerging new therapies. The management of UC therapy should be guided by the endoscopic extent of inflammation, disease severity, and prognostic factors of poor outcome. Complete remission, defined as durable symptomatic and endoscopic remission without corticosteroid therapy, is the desired treatment goal. SUMMARY: This review focuses on treatment recommendations for different clinical scenarios in moderate-to-severe UC: Active UC of any extent not responding to aminosalicylates, steroid-dependent UC, steroid-refractory UC, immunomodulator-refractory UC, and acute severe UC. Comprehensive treatment algorithms for daily clinical practice were developed based on published guidelines and current literature. Key Messages: While current treatment options including a number of biologicals and small molecules have evolved UC treatment to achieve sustained remission in a majority of patients, upcoming treatment options with different molecular pathways and different modes of actions will further increase the need for personalized medicine.

Position statement on the use of biosimilars in inflammatory bowel disease.

Biologics are effective and have a good safety profile in the treatment of inflammatory bowel disease. Biosimilars have recently become available as treatment option. They are biological agents that are highly similar to the original biologic compound in their structure, biological activity, efficacy and safety. This position paper summarises current knowledge on biosimilars and presents its statements on regulatory issues and clinical situation in order to provide clinicians adequate information for them to reach informed and appropriate shared decision-making with their patients.

Deregulation of transcription factors controlling intestinal epithelial cell differentiation; a predisposing factor for reduced enteroendocrine cell number in morbidly obese individuals.

Morbidly obese patients exhibit impaired secretion of gut hormones that may contribute to the development of obesity. After bariatric surgery there is a dramatic increase in gut hormone release. In this study, gastric and duodenal tissues were endoscopically collected from lean, and morbidly obese subjects before and 3 months after laparoscopic sleeve gastrectomy (LSG). Tissue morphology, abundance of chromogranin A, gut hormones, α-defensin, mucin 2, Na+/glucose co-transporter 1 (SGLT1) and transcription factors, Hes1, HATH1, NeuroD1, and Ngn3, were determined. In obese patients, the total number of enteroendocrine cells (EEC) and EECs containing gut hormones were significantly reduced in the stomach and duodenum, compared to lean, and returned to normality post-LSG. No changes in villus height/crypt depth were observed. A significant increase in mucin 2 and SGLT1 expression was detected in the obese duodenum. Expression levels of transcription factors required for differentiation of absorptive and secretory cell lineages were altered. We propose that in obesity, there is deregulation in differentiation of intestinal epithelial cell lineages that may influence the levels of released gut hormones. Post-LSG cellular differentiation profile is restored. An understanding of molecular mechanisms controlling epithelial cell differentiation in the obese intestine assists in the development of non-invasive therapeutic strategies.

Prevalence of past-year dental visit among US adults, 1999-2010: comparison of trends and estimates between the Behavioral Risk Factor Surveillance System and three national surveys.

OBJECTIVES: To compare estimated prevalence of past-year dental visit (PPYDV) among US adults aged ≥18 years from the Behavioral Risk Factor Surveillance System (BRFSS) to estimates from the Medical Expenditure Panel Survey (MEPS), National Health Interview Survey (NHIS), and National Health and Nutrition Examination Survey (NHANES). METHODS: We estimated PPYDV adjusted for covariates (age, race/ethnicity, education level, poverty status, edentulism) using BRFSS, MEPS, and NHIS 1999-2010, and NHANES 1999-2004. We tested trend in overall PPYDV for BRFSS, MEPS, and NHIS from 1999-2010. For 2002 and 2010, we calculated absolute differences (AD) and 95% confidence intervals (CI) in PPYDV between BRFSS and each of the other surveys overall and among subpopulations defined by covariates. We pooled NHANES 1999-2004 data for comparison with BRFSS 2002. RESULTS: From 1999 to 2010, BRFSS (68.5% vs. 67.5%), MEPS (43.5% vs. 39.7%), and NHIS (63.3% vs. 59.7%) showed small but significant decreases in overall PPYDV. In 2002, estimates for overall PPYDV were highest for BRFSS (70.0%) and lowest for MEPS (43.9%) with estimates for NHIS (61.5%) and NHANES (1999-2004: 58.1%) in between; the largest AD (26.2%, 95% CI: 25.0%-27.3%) was between BRFSS and MEPS. ADs were consistent in 2002 and 2010, overall and by covariates, except among edentate persons, where PPYDV estimates from BRFSS and NHIS were similar. CONCLUSIONS: Estimates of PPYDV from BRFSS were notably higher than estimates from MEPS, NHIS, or NHANES except among the edentate. Trends in PPYDV over time, however, were consistent across all surveys.

An Unusual Cause of Rectal Stenosis.

Solitary rectal ulcer syndrome (SRUS) is a benign disease that is often misdiagnosed. It is characterized by a combination of symptoms, endoscopic findings and histology. Patients present with constipation, rectal bleeding, mucous discharge, pain and a sensation of incomplete defecation. There are many different manifestations of this disease, with or without rectal prolapse. We report an unusual presentation of SRUS as a circular stenosis in a middle-aged male.

Monitoring colonoscopy withdrawal time significantly improves the adenoma detection rate and the performance of endoscopists.

BACKGROUND AND STUDY AIMS: The recommended minimum withdrawal time for screening colonoscopy is 6 minutes. Adenoma detection rates (ADRs) increase with longer withdrawal times. We aimed to compare withdrawal times and ADRs of endoscopists unaware of being monitored vs. aware. PATIENTS AND METHODS: Seven experienced gastroenterologists prospectively performed 558 screening colonoscopies during a 9-month period in a Swiss University hospital. Colonoscopy withdrawal times were first measured without the gastroenterologists' knowledge of being monitored (n = 355 colonoscopies) and then with their knowledge (n = 203 colonoscopies). RESULTS: The median withdrawal time when gastroenterologists were unaware of being monitored was 4.5 minutes (interquartile range [IQR] 4 ­â€Š5.5 minutes) without intervention and 6 minutes (IQR 4 ­â€Š9 minutes) with intervention, increasing significantly to 7.3 minutes (IQR 6.5 ­â€Š9 minutes) and 8 minutes (IQR 7 ­â€Š11 minutes), respectively, when they were aware of being monitored (P < 0.001 both for colonoscopies with and without intervention). The ADR increased from 21.4 % when the gastroenterologists were unaware of being monitored to 36.0 % when they were aware (P < 0.001). In the multivariate regression model, the endoscopists knowing they were being monitored was the strongest factor associated with ADR (odds ratio 4.417; 95 % confidence interval [CI] 2.241 ­â€Š8.705; P < 0.001). CONCLUSIONS: Colonoscopy withdrawal time in unmonitored gastroenterologists is shorter than recommended and increases with awareness of monitoring. ADR significantly increases when gastroenterologists are aware of being monitored. Implementation of systematic monitoring, and analysis of withdrawal time and ADR for each endoscopist may help to increase the ADR.

Hyposalivation and dietary nutrient intake among community-based older Japanese.

AIM: Saliva is important for maintaining oral function and regulating oral health. Reduced saliva flow rate, which is common among older adults, has been reported to be associated with perceived chewing and swallowing difficulties; however, its relationship to actual nutrient intake is unclear. The aim of the present cross-sectional study was to evaluate the relationship between hyposalivation and nutrient intake among older Japanese adults. METHODS: The participants were 352 community-based Japanese aged 80 years. A stimulated salivary flow rate <0.5 mL/min was defined as hyposalivation. Multivariable analysis of differences in nutrient and food intake outcome variables, which were collected through a validated food frequency questionnaire, between groups with/without hyposalivation was carried out using general linear models. Models included adjustment for number of teeth, denture use, sex, income, education, body mass index, smoking status, alcohol use, diabetes, medication, activities of daily living, depression and total calorie intake. RESULTS: The hyposalivation group had significantly lower intake of n-3 polyunsaturated fatty acid, potassium, vitamin D, vitamin E, vitamin B6 and folate than the group without hyposalivation (P < 0.05) after adjusting for confounders. Vegetable, fish and shellfish consumption was significantly lower in the hyposalivation group (P < 0.05). CONCLUSIONS: Dietary intake was poorer in those with hyposalivation than among those without. A decrease in stimulated salivary flow rate could have negative effects on geriatric nutrition.

Feasibility study of a salivary occult blood test to correlate with periodontal measures as indicators of periodontal inflammation in a population of pregnant women.

The purpose of this feasibility study was to investigate the correlation of a salivary occult blood test (SOBT) with traditional periodontal measures to assess the feasibility of the SOBT as a measure of periodontal inflammation in a population of women during pregnancy. Considering the limitations of the previous SOBT studies, this study evaluated correlation of the Perioscreen Sunstar SOBT with traditional measures from a full mouth periodontal examination. Data were collected 3 times during pregnancy (12-14, 24-28, and 36 weeks) from women participating in an ongoing study of pregnancy and inflammation. Descriptive statistics and correlations were generated for SOBT scores with periodontal measures. Preliminary data were analyzed from 7 women with 3 visits, 7 with 2, and 9 with 1 visit. For these 44 visits' data, the mean percent of sites with bleeding on probing (BOP) for SOBT scores = 0, 2, and 5 was 58% ± 18%, 68% ± 14%, and 72% ± 19%, respectively. Correlations for percent of sites with BOP and continuous SOBT score was 0.301, P-value = 0.0469 and dichotomous SOBT was 0.32, P-value = 0.0339. Results for feasibility, measured as recruitment of participants, acceptance of protocols, distribution of periodontal inflammation and preliminary correlations, support SOBT as a correlated marker of periodontal inflammation in this population of pregnant women.

Longitudinal relationship between metabolic syndrome and periodontal disease among Japanese adults aged ≥70 years: the Niigata Study.

BACKGROUND: There has been little evaluation in longitudinal epidemiologic studies of the effect of metabolic syndrome (MetS) on periodontal status. The specific aim of this longitudinal study is to investigate whether MetS in the Japanese population could be a risk factor for periodontal disease. METHODS: A total of 125 older adults from Japan for whom data were available for the years 2003 to 2006 were selected for the current study. Full-mouth periodontal status, measured as clinical attachment level (CAL), was recorded at baseline and in follow-up examinations. Development of periodontal disease was considered to be ≥2 teeth demonstrating a longitudinal loss of proximal attachment of ≥3 mm at the follow-up dental examination. A multivariable Poisson regression model with robust error variance was used to evaluate the association of MetS defined by the modified National Cholesterol Education Program Adult Treatment Panel III criteria with development of periodontal disease. Adjustments for sex, income, education, smoking status, number of teeth at baseline, mean CAL at baseline, pattern of visits to a dentist, and brushing frequency were considered. RESULTS: The prevalence of MetS was 21.6% (27/125). Study participants with MetS were approximately 2.6 times more likely to develop periodontal disease (adjusted relative risk 2.58, 95% confidence interval 1.17 to 5.67) after simultaneous adjustment for other covariates. CONCLUSIONS: These findings support the hypothesis that MetS may be a risk factor for periodontal disease in older Japanese individuals. Additional studies with larger, more diverse populations and more complete information are needed to substantiate the findings.

Is there an Appalachian disparity in dental caries in Pennsylvania schoolchildren?

OBJECTIVES: To determine whether there is an Appalachian disparity in caries prevalence or extent in children living in Pennsylvania. METHODS: We conducted a cross-sectional clinical assessment of caries in a sample representing 1st, 3rd, 9th, and 11th grade students across Pennsylvania. We used logistic regression and zero-inflated negative binomial regression controlling for age to examine the association of residence in an Appalachian county with caries prevalence and extent in the primary and permanent dentitions. RESULTS: Compared with children living outside Appalachia, more children living in Appalachia had a dft >0 (OR = 1.37, 95% CI = 1.07-1.76) and more had a DMFT >0 (OR = 1.32, 95% CI = 1.06-1.64). In addition, compared with children living outside Appalachia, children living in Appalachia had a greater primary but not permanent caries extent (IRR = 1.10, 95% CI = 1.01-1.19). CONCLUSIONS: We found Appalachian disparities in caries prevalence in both the primary and permanent dentitions and an Appalachian disparity in caries extent in the primary dentition. None of the disparities was moderated by age. This suggests that the search for the mechanism or mechanisms for the Appalachian disparities should focus on differential exposures to risk factors occurring prior to and at the start of elementary school.

Oral health status: relationship to nutrient and food intake among 80-year-old Japanese adults.

OBJECTIVES: The aim of this cross-sectional study was to investigate the relationship of oral health status defined on the basis of presence of posterior occluding pairs (POPs) and adequacy of removable denture fit as determined by self-report to nutrient and food intake among older Japanese. METHODS: The subjects were 353 Japanese aged 80 years in 2008 and were classified into four groups according to the number of POPs, defined as pairs of occluding natural, restored, or fixed prosthetic postcanine teeth (range: 0-8) and removable denture status. The groups were: (i) good dentition (n = 56; 8 POPs and no removable prosthesis), (ii) well-fitting dentures (n = 158; <8 POPs with self-reported good-fitting dentures), (iii) ill-fitting dentures (n = 70; <8 POPs with self-reported ill-fitting dentures), and (iv) compromised dentition (n = 69; <8 POPs and no removable prosthesis). Multivariable analysis of the differences in nutrient and food intake outcome variables which were collected via validated food frequency questionnaire among the four oral health status groups was conducted using general linear models. Results: Intake of multiple nutrients was significantly (P < 0.05) lower in the group with ill-fitting dentures or compromised dentition than in the good dentition group. Vegetable, fish, and shellfish consumption was significantly lower in the ill-fitting dentures or compromised dentition groups. No significant differences were seen in dietary intake between the well-fitting dentures and good dentition groups. Conclusions: Dietary intake was poorer in those with self-perceived ill-fitting dentures or fewer POPs than among those having all POPs. Regular dental care to maintain intact dentition, as well as dental treatment to replace missing teeth and ensure adequate denture fit and function, may be important to the diet intake and subsequent nutritional status of older Japanese.

Diagnostic yield of endoscopy in patients with abdominal complaints: incremental value of faecal calprotectin on guidelines of appropriateness.

BACKGROUND: European Panel on the Appropriateness of Gastrointestinal Endoscopy (EPAGE) criteria have been developed to increase diagnostic yield, but their predictive value is limited. We investigated the incremental diagnostic value of faecal calprotectin to EPAGE criteria. METHODS: In a post-hoc analysis of a prospective study, EPAGE criteria were applied to 298 of 575 (51.8%) patients who had undergone esophagogastroduodenoscopy (EGD), colonoscopy or both for abdominal complaints at the Division of Gastroenterology & Hepatology at the University Hospital Basel in Switzerland. Faecal calprotectin was measured in stool samples collected within 24 hours before the investigation using an enzyme-linked immunosorbent assay. Final endoscopic diagnoses were blinded to calprotectin values. RESULTS: Of 149 EGDs and 224 colonoscopies, 17.6% and 14.7% respectively were judged inappropriate by EPAGE criteria. Appropriate or uncertain indications revealed more endoscopic findings in both EGD (46.3% vs. 23.1%, P = 0.049) and colonoscopy (23.6% vs. 6.1%, P = 0.041) than inappropriate indications. Median calprotectin levels were higher (81.5 µg/g, interquartile range 26-175, vs. 10 µg/g, IQR 10-22, P < 0.001) and testing was more often positive (>50 µg/g) in patients with endoscopic findings, both in EGD (58.2% vs. 33.0%, P = 0.005) and in colonoscopy (57.3% vs. 7.4%, P < 0.001). The use of faecal calprotectin in addition to EPAGE criteria improved the risk reclassification of patients by endoscopic findings. The calculated net reclassification index was 37.8% (P = 0.002) for EGD and 110.9% (P <0.001) for colonoscopy, thus improving diagnostic yield to 56.8% and 70.2%, respectively. CONCLUSIONS: The use of faecal calprotectin in addition to EPAGE criteria improved diagnostic yield in patients with abdominal complaints.

Monoclonal antibody testing for fecal calprotectin is superior to polyclonal testing of fecal calprotectin and lactoferrin to identify organic intestinal disease in patients with abdominal discomfort.

BACKGROUND AND AIMS: Fecal calprotectin and lactoferrin are sensitive markers of mucosal inflammation. We compared three different assays in their ability to identify patients with organic intestinal disease. METHODS: In a post-hoc analysis of a prospective study, we examined 405 unselected patients with abdominal complaints referred for endoscopy to the University Hospital Basel, Switzerland. Calprotectin (EK-CAL, Bühlmann Laboratories, Switzerland; PhiCal, Calpro AS, Norway) and lactoferrin (IBD-Scan, Techlab, USA) were measured using enzyme-linked immunosorbent assays. The presence of a clinically significant endoscopic finding was the primary endpoint of the study. Final diagnoses were adjudicated blinded to calprotectin values. RESULTS: The prevalence of organic intestinal disease was 35.3%. Receiver operating characteristics analysis calculated an area under the curve (AUC) for EK-CAL of 0.918, which was significantly better than for PhiCal (AUC 0.842, P<0.001) and IBD-Scan (AUC 0.830, P=0.003) to identify patients with organic intestinal disease. Overall test accuracy was 88.1% for EK-CAL, 83.7% for PhiCal, and 81.3% for IBD-Scan. Optimal cut-off value calculated for PhiCal and IBD-Scan were lower than recommended by the manufacturer. CONCLUSIONS: Monoclonal testing of calprotectin is superior to both polyclonal calprotectin testing and fecal lactoferrin in identifying symptomatic patients with organic intestinal disease.

Dietary antioxidants and periodontal disease in community-based older Japanese: a 2-year follow-up study.

OBJECTIVE: To investigate the longitudinal relationship between the intake of dietary antioxidants and periodontal disease in community-dwelling older Japanese. DESIGN: A retrospective cohort study, with a follow-up of 2 years (2003-2005). Intakes of dietary antioxidants (vitamin C, vitamin E, α-carotene and ß-carotene) were assessed with a validated FFQ. Participants were classified by tertile of antioxidant intake. Full-mouth periodontal status, measured as the clinical attachment level, was recorded at baseline and follow-up examinations. Periodontal disease progression was considered as loss of attachment of 3 mm or greater over the study period at the interproximal site for each tooth. Finally, the number of teeth with periodontal disease progression per person was calculated and was used as the outcome. Poisson regression analysis was conducted, with dietary antioxidants as the main exposure, to estimate their influence on the number of teeth with periodontal disease progression. SETTING: Niigata City (Japan). SUBJECTS: Dentate individuals aged 75 years in 2003, for whom data were available, were included in the analyses (n 264). RESULTS: A higher intake of dietary antioxidants was inversely associated with the number of teeth with periodontal disease progression, controlling for other variables. The multivariate-adjusted incidence rate ratios in the first, second and third tertiles were 1·00, 0·76 (95 % CI 0·60, 0·97) and 0·72 (95 % CI 0·56, 0·93) for vitamin C; 1·00, 0·79 (95 % CI 0·62, 0·99) and 0·55 (95 % CI 0·42, 0·72), for vitamin E; and 1·00, 1·02 (95 % CI 0·81, 1·29) and 0·73 (95 % CI 0·56, 0·95) for ß-carotene. CONCLUSIONS: The study results suggest that higher intake of antioxidants may mitigate periodontal disease in community-dwelling older Japanese.

First-line therapies in inflammatory bowel disease.

BACKGROUND AND AIMS: Medical therapy of inflammatory bowel disease (IBD) is becoming more complex, given the increasing choice of drugs to treat Crohn's disease (CD) and ulcerative colitis (UC). We aimed to summarize the current guidelines for first-line treatments in IBD. METHODS: An extensive literature search with focus on the guidelines of the European Crohn's and Colitis Organisation for the diagnosis and treatment of CD and UC was performed. First-line treatments were defined as the following drug categories: 5-aminosalicylates, budesonide, systemic steroids, azathioprine, 6-mercaptopurine, methotrexate, infliximab, adalimumab and certolizumab pegol. The following drug categories were not included: cyclosporine and tacrolimus (not yet approved by Swissmedic for IBD treatment). RESULTS: Treatment recommendations for the following clinically frequent situations are presented according to disease severity: ileocecal CD, colonic CD, proximal small bowel CD and perianal CD. For UC the following situations are presented: ulcerative proctitis, left-sided colitis and pancolitis. CONCLUSIONS: We provide a summary on the use of first-line therapies for clinically frequent situations in patients with CD and UC.

Therapy of steroid-resistant inflammatory bowel disease.

BACKGROUND AND AIMS: Although systemic corticosteroids are successfully administered for the induction of clinical response and remission in the majority of patients with inflammatory bowel disease (IBD) presenting with a flare, a proportion of these patients demonstrate a primary nonresponse to steroids or in the case of an initial response, they develop a resistance or a steroid dependence. Long-term therapy with corticosteroids for treatment of IBD should be avoided, given the high frequency of adverse treatment effects. Knowledge about treatment strategies in case of steroid nonresponse is therefore highly relevant. METHODS: A systematic literature research was performed using Medline and Embase to summarize the currently recommended treatment strategies for steroid-resistant IBD. RESULTS: Treatment of steroid-resistant Crohn's disease is based on the introduction of immunomodulators such as azathioprine, 6-mercaptopurine or methotrexate, the anti-TNF drugs infliximab, adalimumab and certolizumab pegol. In the case of steroid resistance in ulcerative colitis, aminosalicylates, the above-mentioned immunomodulators, infliximab, adalimumab or calcineurin inhibitors such as ciclosporin or tacrolimus may be administered. CONCLUSION: This review summarizes the current evidence for treating steroid-resistant IBD.