Perioperative Enhanced Recovery Concepts Significantly Improve Postoperative Outcome in Patients with Crohn`s Disease.

BACKGROUND AND AIMS: Despite recent advancements in medical and surgical techniques in patients suffering from Crohn`s Disease (CD), postoperative morbidity remains relevant due to a long-standing, non-curable disease burden. As demonstrated for oncological patients, perioperative enhanced recovery concepts provide great potential to improve postoperative outcome. However, robust evidence about the effect of perioperative enhanced recovery concepts in the specific cohort of CD patients is lacking. METHODS: In a prospective single-center study, all patients receiving ileocecal resection due to CD between 2020 and 2023 were included. A specific perioperative enhanced recovery concept (ERC) was implemented and patients were divided into two groups (before and after implementation). The primary outcome focused on postoperative complications as measured by the Comprehensive Complication Index (CCI), secondary endpoints were severe complications, length of hospital stay, and rates of re-admission. RESULTS: 83 patients were analyzed of which 33 patients participated in the enhanced recovery program (postERC). While patient characteristics were comparable between both groups, ERC resulted in significantly decreased rates of overall and severe postoperative complications (CCI: 21.4 versus 8.4, p=0.0036; Clavien Dindo >2: 38% versus 3.1%, p=0.0002). Additionally, postERC-patients were earlier ready for discharge (6.5 days versus 5 days, p=0.001) and rates of re-admission were significantly lower (20% versus 3.1%, p=0.03). In a multivariate analysis, the recovery concept was identified as independent factor to reduce severe postoperative complications (p=0.019). CONCLUSION: A specific perioperative enhanced recovery concept significantly improves the postoperative outcome of patients suffering from Crohn`s Disease.

Alterations in Gut Microbiota as Early Biomarkers for Predicting Inflammatory Bowel Disease Onset and Progression: A Systematic Review.

Inflammatory bowel disease (IBD) is a chronic ailment impacting the digestive system, triggered by an unusual reaction of the immune system. It includes two types of diseases: ulcerative colitis and Crohn's disease. Nonetheless, the diagnosis and evaluation of disease progression in IBD are difficult due to the absence of distinct indicators. While conventional biomarkers from blood plasma and feces, such as C-reactive protein, fecal calprotectin, and S100A12, can be employed to gauge inflammation, they are not exclusive to IBD. There is a broad consensus that intestinal microorganisms significantly contribute to the onset of intestinal imbalance, a condition intimately linked with the cause and development of IBD. Numerous studies have indicated that the makeup of intestinal microorganisms varies between individuals with IBD and those who are healthy, particularly concerning the diversity of microbes and the proportional prevalence of certain bacteria. A total of 1475 records underwent examination. Following the eligibility assessment, 17 reports were considered. The final review encompassed 12 studies, as five articles were excluded due to insufficient details regarding cases, controls, and comparability. This article suggests that gut microbiota has potential biomarkers for the noninvasive evaluation of IBD activity. Recognizing the microbiome linked with disease activity paves the way for the development of a group of microbiota-derived indicators to evaluate the initiation and advancement of IBD. This article discusses whether changes in gut microbial composition can serve as early indicators of IBD onset and progression.

The Impact of Microbiome Interventions on the Progression and Severity of Inflammatory Bowel Disease: A Systematic Review.

Inflammatory bowel disease (IBD), comprising Crohn's disease (CD) and ulcerative colitis (UC), is characterized by chronic intestinal inflammation. The dysbiotic gut microbiome likely contributes to IBD pathogenesis. Microbiome-directed therapies such as fecal microbiota transplantation (FMT), probiotics, and synbiotics may help induce and maintain remission. This systematic review aimed to determine the efficacy of microbiome interventions compared to standard therapy or placebo for IBD treatment. PubMed, EMBASE, Cochrane CENTRAL, and Web of Science were searched for randomized controlled trials on microbiome interventions in IBD from inception to October 2023. The risk of bias was assessed using Cochrane tools. Outcomes included disease activity, endoscopy, histology, quality of life, and adverse events. A total of 18 randomized controlled trials were included. Three trials found intensive (i.e., high frequency of administration and/or large volumes of fecal material) multi-donor FMT superior to autologous FMT or glucocorticoids for UC remission induction. Seven placebo-controlled trials demonstrated higher remission rates with FMT, especially intensive protocols, versus control for mild-to-moderate UC. However, a single FMT did not prevent relapses. Seven probiotic trials showed the potential to improve UC activity and maintain remission. One synbiotic trial reported reduced inflammation and symptoms versus placebo. Serious adverse events were rare. Small sample sizes and protocol heterogeneity limited the conclusions. Current evidence indicates the potential benefits of microbiome interventions, particularly intensive multi-donor FMT, for inducing and maintaining remission in UC. Probiotics may also improve outcomes. Adequately powered trials using standardized protocols are still needed to firmly establish efficacy and safety. Microbiome-directed therapies represent a promising approach for improving IBD outcomes.

The need for surgery in pediatric patients with inflammatory bowel disease treated with biologicals.

PURPOSE: Inflammatory bowel disease (IBD) in childhood often presents with a more extensive and more aggressive disease course than adult-onset disease. We aimed to evaluate if biological treatment started in childhood decreases the need for intestinal surgery over time. METHODS: This was a retrospective, single-center, cohort study. All pediatric patients with IBD initiated to biological therapy at the Children's Hospital, were included in the study and followed up to the first surgical procedure or re-operation in their adulthood or until 31.12.2021 when ≥ 18 of age. Data were collected from the pediatric registry of IBD patients with biologicals and medical charts. RESULTS: A total of 207 pediatric IBD patients were identified [150 with Crohn´s disease (CD), 31 with ulcerative colitis (UC), 26 with IBD unclassified (IBDU)] of which 32.9% (n = 68; CD 49, UC 13, IBDU 6) underwent intestinal surgery. At the end of a median follow-up of 9.0 years (range 2.0-25.9), patients reached a median age of 21.4 years (range 18-36). Patients who had intestinal surgery in childhood were more likely to have IBD-related surgery also in early adulthood. The duration of the disease at induction of the first biological treatment emerged as the only risk factor, with a longer duration in the surgical group than in patients with no surgery. CONCLUSION: Despite initiation of biological treatment, the risk of intestinal surgery remains high in pediatric IBD patients and often the need for surgery emerges after the transition to adult IBD clinics.

Periodontitis and Inflammatory Bowel Disease: A Review.

The complex relationship between periodontitis (PD) and inflammatory bowel disease (IBD) has received significant attention in recent studies. Emerging evidence suggests that the oral-gut axis plays a pivotal role in their interaction. This review provides a comprehensive, up-to-date analysis of original research from 2003 to 2023 on the PD-IBD relationship and aims to be a reference for future research. Relevant literature was sourced from the PubMed database using the keywords "periodontitis" and "inflammatory bowel disease". Additionally, a manual library search and a review of bibliographies were conducted. Of the 297 articles retrieved, 27 studies were chosen for final review. Out of these, 21 studies (78%), including both in vitro and in vivo research, indicated an association between PD and IBD. While many studies confirm a bi-directional relationship, others refute it or deem it clinically irrelevant. There is a need for more accessible studies, such as randomized trials, which also investigate the factors that could influence the outcomes to clarify the exact molecular mechanisms and clinical implications of this complex relationship.

Circulating leptin levels in the assessment of Crohn’s disease activity and its relation to nutritional status / Los niveles circulantes de leptina en la evaluación de la actividad de la enfermedad de Crohn y su relación con el estado nutricional

Objective: to evaluate leptin levels and its relation to nutritional status in Crohn’s disease (CD).Methods: the study included 154 CD patients and healthy controls. Leptin level was determined before treatment. Nutrition levels were assessedusing the Nutrition Risk Screening 2002 (NRS-2002) and Patient-Generated Subjective Global Assessment (PG-SGA). Indicators included bodymass index (BMI), mid-arm circumference, the circumference of the upper-arm muscle, triceps skinfold thickness, and circumference of legs.Results: leptin levels differed between CD patients (1,025 ± 874 ng/ml) and controls (18,48 ± 1,222 ng/ml). Significant differences were seenin NRS-2002, PG-SGA scores, BMI and other nutritional indicators. Negative correlations were observed between leptin and NRS-2002, PG-SGAscores, while positive correlations were observed with other nutritional indicators. The receiver operating characteristic (ROC) curve showedassociation between leptin and the diagnosis of CD, suggesting leptin concentration below 803.02 ng/ml as a threshold for CD.Conclusion: dysfunctional leptin regulation may relate to poor nutritional status associated with CD. The leptin level is thus an additional toolfor evaluating CD patients, predicting disease activity and clinical response. Leptin may be a potential target for intervention in CD to improvenutritional status.(AU)

Objetivo: evaluar los niveles de leptina y su relación con el estado nutricional en la enfermedad de Crohn (EC).Métodos: se incluyeron 154 pacientes con EC y controles sanos. El nivel de leptina se determinó antes del tratamiento. La situación nutricionalse evaluó mediante el examen de riesgo nutricional 2002 (NRS-2002) y la Valoración Global Subjetiva Generada por el Paciente (VGS-GP). Losindicadores incluyen el índice de masa corporal (IMC), la circunferencia media del brazo, la circunferencia del músculo superior del brazo, elgrosor del pliegue cutáneo del tríceps y la circunferencia de las piernas.Resultados: los niveles de leptina difirieron entre los pacientes con EC (1.025 ± 874 ng/ml) y los controles (18.48 ± 1.222 ng/ml). Se obser-varon diferencias significativas en NRS-2002, puntajes de VGS-GP, IMC y otros indicadores nutricionales. Se observaron correlaciones negativasentre leptina y NRS-2002, puntuaciones de VGS-GP, mientras que se observaron correlaciones positivas con otros indicadores nutricionales.La curva ROC mostró asociación entre leptina y el diagnóstico de EC, sugiriendo concentraciones de leptina por debajo de 803,02 ng/ml comoumbral para EC.Conclusión: puede relacionarse la alteración en la regulación de la leptina con la peor situación nutricional en enfermos con EC. La leptinapuede ser un objetivo potencial para la intervención en EC a fin de mejorar el estado nutricional.(AU)

Drug levels of VEDOLIZUMAB in patients with pediatric-onset inflammatory bowel disease in a real-life setting.

Vedolizumab (VDZ) is used off-label in pediatric inflammatory bowel disease (PIBD). There are less data on drug levels to achieve and maintain remission in children. We aimed to study vedolizumab (VDZ) trough levels in a pediatric population in a real-life setting. We traced 50 patients with PIBD receiving VDZ treatment at our hospital, reviewed their treatment protocol, trough levels, and antidrug antibodies, and compared those to fecal calprotectin (FC) levels and achievement of corticosteroid-free maintenance therapy (CF). VDZ trough level was available from 198 samples during a median follow- up of 12.6 months. Proceeding to maintenance therapy was associated with a decline in FC but not with VDZ trough levels that were comparable between patients with FC < 100 µg/g (remission), 100-1000 µg/g, or > 1000 µg/g at 3 months (mean levels of 36.8, 28.6, and 27 µg/mL, respectively p = 0.188). At 3 months, patients achieving CF (41%) and those on corticosteroids had comparable VDZ trough levels (33 vs. 27.5 µg/mL, respectively). At 6 months, the trough level was similar in groups with FC < 100 µg/g or FC > 1000 µg/g (31.5 and 27.6 µg/mL, p = 0.859). Treatment intensification did not improve the achieved CF at 12 months. None developed drug antibodies nor discontinued the therapy for an adverse event.   Conclusion: VDZ was a well-tolerated and safe biologic treatment. A positive response on gut inflammation after induction predicted proceeding to maintenance therapy whereas trough levels did not. A VDZ trough level associated with clinical remission or continuing with VDZ treatment could not be determined. What is Known: • In pediatric inflammatory bowel disease, vedolizumab is still in off-label use. • The results on the relationship between drug levels of vedolizumab and clinical remission in pediatric patients are contradictory. What is New: • This real-life setting in pediatric-onset inflammatory bowel disease showed no benefit of therapy enhancement during a median follow-up of one year. • Trough levels of vedolizumab were not associated with therapy outcomes.

Psychological disorders and coping strategies in patients with inflammatory bowel disease. Their impact on health-related quality of life

Background and objectives: inflammatory bowel disease (IBD) has a major impact on psychological well-being. This condition is associated with a high level of anxiety and mood disorders, but stress prevalence and how an individual copes with IBD have not been sufficiently explored. The objective of this study was to assess the impact of the disease on psychological disorders and to identify coping strategies used by patients with IBD, as well as to analyze the relationship between these variables and sociodemographic and clinical variables. Methods: a cross-sectional prospective study was performed including 126 consecutive patients. Those with psychiatric conditions prior to the onset of the IBD were excluded. Independent variables were measured using a sociodemographic and clinical questionnaire. The patients completed the Hospital Anxiety and Depression Scale (HADS), the Perceived Stress Scale (PSS) and the BRIEF COPE questionnaire. Quality of life was measured using the nine-item IBD Quality of Life (IBDQ-9). Results: the final cohort comprised 100 patients (37 with ulcerative colitis and 63 with Crohn’s disease). The prevalence rates of the variables of stress, anxiety and depression were high (44 %, 24 % and 14 %, respectively). Stress and depression were higher in females (p < 0.05), without differences regarding other sociodemographic and clinical variables. Moreover, higher levels of anxiety and depression were found to be associated with stress and dysfunctional coping strategies (p < 0.01). Conclusions: patients with IBD, particularly women, have high rates of psychological disorders. Those with anxiety and depression presented more stress and used more dysfunctional strategies. These conditions must be considered for a multidisciplinary management. (AU)

Transient second-degree type 2 atrioventricular block after infliximab infusion in a patient with Crohn’s disease and heterozygous familial hypercholesterolemia

Current treatments for patients in the active phase of Crohn's disease (CD) include conventional treatments and biological treatments. Infliximab (IFX), a TNF-α antagonist, is recommended to induce remission in patients with moderate-to-severe CD who have not responded to conventional therapy. IFX terminates the inflammatory cascade by inhibiting the nuclear factor-κB (NF-κB), mitogen-activated protein kinase (MAPK), and caspase signaling pathways and increases the apoptosis of activated T cells in inflamed tissues. (AU)

To STRIDE or not to STRIDE: a critique of "treat to target" in Crohn´s disease.

INTRODUCTION: The STRIDE consensus suggested to focus on mucosal healing, based on biomarkers and endoscopy, in addition to clinical endpoints as treatment target. This narrative review provides a critique of this concept in Crohn´s disease. AREAS COVERED: We analyze and discuss the limitations of endpoints as targets, their currently limited achievability, and the controversial evidence relating to 'treat to target.' The relevant publications in Pubmed were identified in a literature review with the key word 'Crohn´s disease.' EXPERT OPINION: All targets and endpoints have their limitations, and, even if reached, not all have unequivocally been shown to improve prognosis. The major deficiency of STRIDE is not only the lack of validation and agreement upon endpoints but little evidence of their achievability in a sizable proportion of patients by dose or timing adjustments or switching the medication. Above all, the concept should be based on clear evidence that patients indeed benefit from appropriate escalation of treatment and relevant controlled studies in this regard have been controversial. Until the STRIDE approach is proven to be superior to standard treatment focusing on clinical well-being, the field should remain reluctant and expect more convincing evidence before new targets are approved.

ffectiveness and safety of ustekinumab dose escalation in Crohn’s disease: a multicenter observational study / Efectividad y seguridad del aumento de dosis de ustekinumab en la enfermedad de Crohn: un estudio observacional multicéntrico

Background: ustekinumab has proven effective in Crohn’s disease (CD). However, some patients will partially respond or lose response over time. Data supporting the effectiveness of dose escalation in this scenario is scarce. Aim: to evaluate the effectiveness of ustekinumab dose escalation in CD. Methods: patients with active CD (Harvey-Bradshaw ≥ 5) who had received intravenous (IV) induction and at least a subcutaneous (SC) dose were included in this retrospective observational study. Ustekinumab dose was escalated, either via shortening of the interval to six or four weeks or IV reinduction plus shortening to every four weeks. Results: ninety-one patients were included, and ustekinumab dose was escalated after a median of 35 weeks of treatment. At week 16 after intensification, steroid-free clinical response and remission were observed in 62.6 % and 25.3 % of patients, respectively. Systemic corticosteroids were discontinued in 46.7 % of patients who were on corticosteroids at baseline. Follow-up data beyond week 16 were available for 78 % of patients; at the last visit, 66.2 % and 43.7 % were in steroid-free clinical response and remission, respectively. After a median follow-up of 64 weeks, 81 % of patients were still treated with ustekinumab. Adverse events were reported in 4.3 % of patients; these were all mild and did not lead to hospitalization or discontinuation of treatment. Five patients (5.5 %) underwent surgical resection, with no immediate postsurgical complications. Conclusion: ustekinumab dose escalation was effective in recapturing response in over half of the patients. These findings suggest that dose escalation should be considered in patients who experience loss or partial response to the standard maintenance.(AU)

FiLaC procedure for highly selected anal fistula patients: indications,safety and efficacy from an observational study at a tertiary referral center / Procedimiento FiLaC para pacientes con fístula anal altamente seleccionados: indicaciones, seguridad y eficacia de un estudio observacional en un centro de referencia terciario

Background: the ideal clinical profile of patients or fistula features for fistula laser closure (FiLaC®) technique remain to be established. The aim of this study was to analyze clinical outcomes and the safety profile of FiLaC® in search for an ideal setting for this technique. Methods: a retrospective observational study was performed from a prospective database including all consecutive patients who underwent surgery for anal fistula (AF) with FiLaC® in the coloproctology unit of a tertiary referral center, between October 2015 and December 2021. The FiLaC® procedure was offered to AF patients who were considered to be at risk of fecal incontinence. Fistulas were described according to Parks’ classification and categorized as complex or simple according to the American Gastroenterological Association (AGA) guidelines. Healing was defined by the closure of the internal and external openings for at least six months. Predictive factors of AF healing were investigated. Results: a total of 36 patients were included, with a mean age of 48 ± 13.9 years. Twenty patients (55.6 %) were male and 13 patients (36 %) had Crohn’s disease (CD). Fourteen patients (38.8 %) had a complex fistula. The primary and secondary healing rates were 55.6 % and 91.7 %, respectively, during a median follow-up time of 12 months (IQR 7-29). No fecal continence impairment was registered in any case. The proportion of patients with primary healing was significantly higher in CD patients (76.9 % vs 43.5 %, p = 0.048). Conclusions: FiLaC® is a sphincter-preserving procedure with an excellent safety profile and reasonable success rate despite of the strict patient selection. This technique may be attractive for patients with CD due to its higher primary healing rate.(AU)

A rare case of an esophageal neuroendocrine carcinoma arising on an endoscopic resection scar / Un caso raro de esófago carcinoma neuroendocrino que surge en una endoscópica cicatriz de resección

Here we report a case of a 61-year-old woman who underwent en-bloc endoscopic submucosal dissection (ESD) of a 10mm depressed lesion (Paris 0-IIc, Figure A) in the mid-esophagus. Histopathology showed a lesion with high-grade squamous dysplasia (R0). On follow-up endoscopy at 6 and 12 months the scar was regular, without signs of recurrence. Seven months after the last endoscopy, the patient presented with chest pain and dysphagia. Endoscopy showed an ulcero-vegetating tumor with 3cm at the same location of previous ESD (Figure B), and biopsies showed a poorly differentiated small cell neuroendocrine carcinoma (NEC). Subsequent computed tomography identified peri-tumor and hilar lymph nodes, and an extensive periceliac nodal conglomerate adherent to the liver (stage IV). This is, to our knowledge, the first case described of esophageal NEC arising on the endoscopic resection scar.(AU)

Pharmacological Chemolysis of Uric Acid Lithiasis in A Patient with Crohn’s Disease

Patients with chronic diarrhoea or ileostomies suffer from electrolyte and urinary disorders and are prone to developing uricacid or calcium oxalate stones. Evidence is lacking regarding the management of uric acid stones in patients with inflammatorybowel diseases. We present the case of a male patient with Crohn’s disease and carrying an ileostomy. He was diagnosed with uricacid urolithiasis (stone size of 11 mm located in the left pyeloureteral junction) after presenting to the emergency room during anepisode of left renal colic. Results of the 24-hour urinalysis showed an acidic pH (pH <5), consistent with hyperuricosuria. Thesuspicion of uric acid lithiasis was confirmed after performing an X-ray diffraction analysis of a lithiasic fragment that passedduring acute renal colic. The patient was prescribed with urinary alkalinisers (medical treatment) and dietary recommendations.After 12 months of treatment and urine pH monitoring, the patient achieved complete chemolysis while maintaining the stabilityof his underlying Crohn’s disease. The patient had no complications during follow-up, referring adequate gastrointestinal toleranceto treatment and denying side effects. The patient remains asymptomatic and is being followed-up on an outpatient basis.He continues on prophylactic treatment (Lit-Control® pH Up) to maintain the pH in the non-acidic range. (AU)

Altered fecal bile acid composition in active ulcerative colitis.

BACKGROUND: Disturbed bile acid homeostasis associated with a rise of primary and a decline of secondary bile acids is a consistent finding in inflammatory bowel diseases (IBDs). Whether fecal bile acids may emerge as biomarkers for IBD diagnosis and disease severity is less clear. Our study aimed to identify associations of 18 fecal bile acid species with IBD entity and disease activity. METHODS: Stool samples of 62 IBD patients and 17 controls were collected. Eighteen fecal bile acid species were quantified by LC-MS/MS using stable isotope dilution. Lipid levels normalized to a dry weight of the fecal homogenates and ratios of single bile acid species to total bile acid levels were used for calculations. RESULTS: IBD patients exhibited altered primary and secondary bile acid ratios in stool, with notable distinctions between ulcerative colitis (UC) compared to Crohn's disease (CD) and healthy controls. Fecal calprotectin was negatively correlated with glycolithocholic acid (GLCA) and hyodeoxycholic acid (HDCA) in UC. These bile acids were reduced in stool of UC patients with fecal calprotectin levels > 500 µg/g compared to UC patients with low calprotectin levels. Moreover, negative associations of six secondary bile acids with C-reactive protein (CRP) existed in UC. In CD patients, fecal bile acids did not correlate with CRP or fecal calprotectin. Diarrhoea is common in IBD, and UC patients with diarrhoea had reduced deoxycholic acid (DCA), glycine conjugated DCA (GDCA) and lithocholic acid in stool in contrast to patients with normal stool consistency. Fecal bile acid levels were not associated with diarrhoea in CD patients. UC patients treated with mesalazine had increased levels of fecal GDCA whereas no such changes were observed in CD patients. Bile acid levels of CD and UC patients treated with biologicals or corticosteroids did not change. Relative levels of GHDCA (specificity: 79%, sensitivity: 67%) and glycochenodeoxycholic acid (specificity: 74%, sensitivity: 63%) were the most specific to distinguish UC from CD. CONCLUSION: Disrupted fecal bile acid homeostasis is associated with disease severity and disease symptoms in UC but not in CD, potentially aiding in distinguishing IBD subtypes and classifying the pathophysiology of diarrhoea in UC.

Systematic Review and Meta-Analysis: Prevalence of Non-Alcoholic Fatty Liver Disease and Liver Fibrosis in Patients with Inflammatory Bowel Disease.

BACKGROUND: Non-alcoholic fatty liver disease (NAFLD) is a common concomitant condition in patients with inflammatory bowel disease (IBD). We aim to assess the magnitude of this association. METHODS: We searched MEDLINE, EMBASE and Scopus libraries for the period up to February 2023 to identify studies reporting cohorts of IBD patients in which NALFLD was evaluated. RESULTS: Eighty-nine studies were analyzed. The overall prevalence of NAFLD was 24.4% (95%CI, 19.3-29.8) in IBD, 20.2% (18.3-22.3) in Crohn's disease and 18.5% (16.4-20.8) for ulcerative colitis. Higher prevalence was found in male compared to female patients, in full papers compared to abstracts, and in cross-sectional studies compared to prospective and retrospective ones. The prevalence of NAFLD in IBD has increased in studies published from 2015 onwards: 23.2% (21.5-24.9) vs. 17.8% (13.2-22.9). Diagnostic methods for NAFLD determined prevalence figures, being highest in patients assessed by controlled attenuation parameter (38.8%; 33.1-44.7) compared to ultrasonography (28.5%; 23.1-34.2) or other methods. The overall prevalence of fibrosis was 16.7% (12.2-21.7) but varied greatly according to the measurement method. CONCLUSION: One-quarter of patients with IBD might present with NAFLD worldwide. This proportion was higher in recent studies and in those that used current diagnostic methods.

Fecal short chain fatty acids and urinary 3-indoxyl sulfate do not discriminate between patients with Crohn´s disease and ulcerative colitis and are not of diagnostic utility for predicting disease severity.

BACKGROUND: Urinary 3-indoxyl sulfate levels as well as fecal short chain fatty acid (SCFA) concentrations are surrogate markers for gut microbiota diversity. Patients with inflammatory bowel diseases (IBDs) and patients with primary sclerosing cholangitis (PSC), a disease closely associated with IBD, have decreased microbiome diversity. In this paper, the fecal SCFAs propionate, acetate, butyrate and isobutyrate of patients with IBD and patients with PSC-IBD and urinary 3-indoxyl sulfate of IBD patients were determined to study associations with disease etiology and severity. METHODS: SCFA levels in feces of 64 IBD patients and 20 PSC-IBD patients were quantified by liquid chromatography with tandem mass spectrometry (LC-MS/MS). Urinary 3-indoxyl sulfate levels of 45 of these IBD patients were analysed by means of reversed-phase liquid chromatography-electrospray ionization-tandem mass spectrometry. Feces of 17 healthy controls and urine of 13 of these controls were analyzed in parallel. These cohorts had comparable sex distribution and age. RESULTS: Urinary 3-indoxyl sulfate concentrations (normalized to urinary creatinine levels) was increased (P = 0.030) and fecal isobutyrate levels (normalized to dry weight of the stool sample) of IBD patients were decreased (P = 0.035) in comparison to healthy controls. None of the analyzed metabolites differed between patients with Crohn´s disease (CD) and patients with ulcerative colitis (UC). Fecal acetate and butyrate positively correlated with fecal calprotectin (P = 0.040 and P = 0.005, respectively) and serum C-reactive protein (P = 0.024 and P = 0.025, respectively) in UC but not CD patients. UC patients with fecal calprotectin levels above 150 µg/g, indicating intestinal inflammatory activity, had higher fecal acetate (P = 0.016), butyrate (P = 0.007) and propionate (P = 0.046) in comparison to patients with fecal calprotectin levels < 50 µg/g. Fecal SCFA levels of PSC-IBD and IBD patients were comparable. CONCLUSIONS: Current findings suggest that analysis of urinary 3-indoxyl-sulfate as well as fecal SCFAs has no diagnostic value for IBD and PSC-IBD diagnosis or monitoring of disease severity.

Prioritization in inflammatory bowel disease therapy.

INTRODUCTION: Most guidelines for IBD still recommend step-by-step therapy with initially classic drugs such aminosalicylates (in ulcerative colitis) or steroids but avoid prioritizing certain biological drugs and JAK inhibitors in the complicated course. This review provides an aid to pending therapy decisions. AREAS COVERED: In this review, we analyze the evidence for Crohn's disease as well as ulcerative colitis in order to optimize and 'personalize' the choice of therapy, especially in difficult cases. The relevant publications in Pubmed were identified in a continuous literature review with the key words 'Crohn´s disease' and 'ulcerative colitis.' EXPERT OPINION: Based on this complex data set following standard therapies steroid-refractory Crohn´s disease should preferentially be treated with combined infliximab plus azathioprine or risankizumab, in second line after their failure with ustekinumab or 7adalimumab. In steroid-refractory ulcerative colitis infliximab plus azathioprine or upadacitinib should be preferred in first line, filgotinib, tofacitinib or ustekinumab in second line. A steroid-dependent course in both diseases requires azathioprine or vedolizumab, in second line infliximab or Janus kinase inhibitors. The conclusions drawn from these complex data may be helpful for individual decision making in daily clinical practice.

Symptoms and symptom clusters in patients newly diagnosed with inflammatory bowel disease: results from the IBSEN III Study.

BACKGROUND: Patients with inflammatory bowel disease report multiple symptoms, but the relationships among co-occurring symptoms are poorly understood. This study aimed to examine the prevalence of symptoms and explore symptom clusters and possible associations between symptom clusters and socio-demographic and clinical variables in patients newly diagnosed with inflammatory bowel disease. METHODS: The IBSEN III study is a prospective population-based inception cohort of patients with inflammatory bowel disease. This study used patient data from the three largest hospitals in the study catchment area. The Memorial Symptom Assessment Scale was used to assess the prevalence of symptoms. Symptom clusters were identified using principal component analysis. Possible associations between socio-demographic and clinical variables and symptom cluster membership were estimated using regression analysis. RESULTS: Of the 573 patients (age, ≥18 years) diagnosed with inflammatory bowel disease, 350 (61.1%) completed the questionnaire (responders). Eleven symptoms were reported by >50% of the responders. The three most prevalent symptoms were bloating (84%), drowsiness (81%), and lack of energy (81%). Three symptom clusters were identified: psychological (56% of the patients), impaired energy (28%), and physical (16%) clusters. Multinomial regression analysis revealed that vitamin D deficiency was significantly associated with the impaired energy cluster (odds ratio=2.49, 95% confidence interval [1.00-6.2], p=0.05). CONCLUSIONS: We found high symptom prevalence in patients newly diagnosed with inflammatory bowel disease. Three distinct symptom clusters were identified, and the psychological cluster includes >50% of the patients. Vitamin D deficiency is the only factor associated with cluster membership, namely the impaired energy cluster.

Inflammatory bowel disease and prostate cancer risk: a two-sample Mendelian randomization analysis.

Background: Previous epidemiological observational studies have reported an association between inflammatory bowel disease (IBD) and prostate cancer (PCa), but the causality is inconclusive. The purpose of this study was to evaluate the causality of IBD on PCa using the mendelian randomization (MR) analysis. Methods: We performed a two-sample MR analysis with public genome-wide association studies (GWAS) data. Eligible instrumental variables (IVs) were selected according to the three assumptions of MR analysis. The inverse-variance weighted (IVW) method was the main method. Complementary methods included the MR-Egger regression, the Weighted Median, the Simple Mode, the Weighted Mode and MR pleiotropy residual sum and outlier (MR-PRESSO) methods. Results: Genetically determined IBD did not have a causal effect on PCa (IVW P > 0.05). Additionally, there was no causal effect of Crohn's disease (CD) and ulcerative colitis (UC) on PCa in the MR analysis (IVW P > 0.05). Results of complementary methods were consistent with those of the IVW method. Conclusions: This study does not support a causal association of IBD on PCa, which is in contrast to most observational studies.