Frailty and Inflammatory Bowel Disease: A Scoping Review of Current Evidence.

Frailty is increasingly recognized as an important concept in patients with Inflammatory Bowel Disease (IBD). The aim of this scoping review is to summarize the current literature on frailty in IBD. We will discuss the definition of frailty, frailty assessment methods, the prevalence of frailty, risk factors for frailty and the prognostic value of frailty in IBD. A scoping literature search was performed using the PubMed database. Frailty prevalence varied from 6% to 53.9%, depending on the population and frailty assessment method. Frailty was associated with a range of adverse outcomes, including an increased risk for all-cause hospitalization and readmission, mortality in non-surgical setting, IBD-related hospitalization and readmission. Therefore, frailty assessment should become integrated as part of routine clinical care for older patients with IBD.

Exposure to Thioguanine During 117 Pregnancies in Women With Inflammatory Bowel Disease.

BACKGROUND: Safety of thioguanine in pregnant patients with inflammatory bowel disease [IBD] is sparsely recorded. This study was aimed to document the safety of thioguanine during pregnancy and birth. METHODS: In this multicentre case series, IBD patients treated with thioguanine during pregnancy were included. Data regarding disease and medication history, pregnancy course, obstetric complications, and neonatal outcomes were collected. RESULTS: Data on 117 thioguanine-exposed pregnancies in 99 women were collected. Most [78%] had Crohn's disease and the mean age at delivery was 31 years. In 18 pregnancies [15%], IBD flared. Obstetric and infectious complications were seen in 15% [n = 17] and 7% [n = 8] of pregnancies, respectively. Ten pregnancies [8.5%] resulted in a first trimester miscarriage, one in a stillbirth at 22 weeks of gestational age and one in an induced abortion due to trisomy 21. In total, 109 neonates were born from 101 singleton pregnancies and four twin pregnancies. One child was born with a congenital abnormality [cleft palate]. In the singleton pregnancies, 10 children were born prematurely and 10 were born small for gestational age. Screening for myelosuppresion was performed in 16 neonates [14.7%]; two had anaemia in umbilical cord blood. All outcomes were comparable to either the general Dutch population or to data from three Dutch cohort studies on the use of conventional thiopurines in pregnant IBD patients. CONCLUSION: In this large case series, the use of thioguanine during pregnancy is not associated in excess with adverse maternal or neonatal outcomes.

Real-world experience of switching from intravenous to subcutaneous vedolizumab maintenance treatment for inflammatory bowel diseases.

BACKGROUND: Subcutaneous (SC) vedolizumab is effective in inflammatory bowel diseases (IBD) when administered after induction with two infusions. AIM: To assess the effectiveness, safety and pharmacokinetics of a switch from intravenous (IV) to SC maintenance vedolizumab in patients with IBD METHODS: In this prospective cohort study, patients with IBD who had ≥4 months IV vedolizumab were switched to SC vedolizumab. We studied the time to discontinuation of SC vedolizumab, adverse events (AEs), changes in clinical and biochemical outcomes and vedolizumab concentrations at baseline, and weeks 12 and 24. RESULTS: We included 82 patients with Crohn's disease (CD) and 53 with ulcerative colitis (UC). Eleven (13.4%) patients with CD and five (9.4%) with UC discontinued SC vedolizumab after a median of 18 (IQR 8-22) and 6 weeks (IQR 5-10), respectively. Four patients with CD switched to a different drug due to loss of response, nine switched back to IV vedolizumab due to adverse events, and three due to needle fear. Common AEs were injection site reactions (n = 15) and headache (n = 6). Median clinical and biochemical disease activity remained stable after the switch. Median serum vedolizumab concentrations increased from 19 µg/ml at the time of the switch to 31 µg/ml 12 weeks after the switch (p < 0.005). CONCLUSIONS: Switching from IV to SC vedolizumab maintenance treatment is effective in patients with CD or UC. However, 9% of patients were switched back to IV vedolizumab due to adverse events or fear of needles.

Comment on Szczubelek et al. Effectiveness of Crohn's Disease Exclusion Diet for Induction of Remission in Crohn's Disease Adult Patients. Nutrients 2021, 13, 4112.

We read with interest the manuscript by Szczubelek et al. [...].

Treatment goals in IBD: A perspective from patients and their partners.

Objective: To identify and compare treatment goals between IBD patients and partners, and how these change upon receiving information. Methods: During a patient information day a self-made survey was distributed before and after a lecture about a physicians' view on treatments goals. Patients and partners were asked for their preferred treatment goals at 6 weeks and at 6 months and could choose between short-term goals (symptom free, improved functioning, better QOL, normal colonoscopy) and long-term goals (prevention of surgery, complications, flares and no steroids). Results: Being "symptom-free" (55.9%) was the preferred goal. Patients with higher disease activity chose more short-term goals (p=0.03) at 6 weeks. Age, gender and education did not affect treatment goals. Partners chose more short-term goals (p=0.03) at 6 weeks. Post-lecture, answers shifter to normal colonoscopy (4.2% versus 18.0%, p=0.001), and a better QOL (21.2% vs 33.3%, p=0.039) as goal at 6-months. Conclusions: Patients' 6-week treatment goals focused on being symptom-free and having a high QOL, especially those patients with high disease activity. Partners chose more short-term goals than patients at 6 weeks. Innovation: General health information can be applied and translated into treatment goals. This may assist in remote shared goal setting and decision making.

Does mucosal inflammation drive recurrence of primary sclerosing cholangitis in liver transplantion recipients with ulcerative colitis?

BACKGROUND: Liver transplantation remains the only effective evidence based treatment for advanced primary sclerosing cholangitis. However, recurrence of disease occurs in approximately 18%. AIMS: This study aimed to assess risk factors of recurrence of primary sclerosing cholangitis. METHODS: A retrospective cohort study was performed on patients undergoing transplantation for recurrence of primary sclerosing cholangitis in two academic centers (Leuven, Belgium and Leiden, The Netherlands). Besides other risk factors, the degree of mucosal inflammation was assessed as a potential risk factor using histological Geboes scores. RESULTS: 81 patients were included, of which 62 (76.5%) were diagnosed with ulcerative colitis. Seventeen patients (21.0%) developed rPSC during a median follow-up time of 5.2 years. In a subset of 42 patients no association was found between the degree of mucosal inflammation and recurrence, using both original Geboes scores and multiple cut-off points. In the total cohort, cytomegaloviremia post-transplantation (HR: 4.576, 95%CI 1.688-12.403) and younger receiver age at time of liver transplantation (HR: 0.934, 95%CI 0.881-0.990) were independently associated with an increased risk of recurrence of disease. CONCLUSION: This study found no association between the degree of mucosal inflammation and recurrence of primary sclerosing cholangitis. An association with recurrence was found for cytomegaloviremia post-liver transplantation and younger age at time of liver transplantation.

Risk of impaired nutritional status and flare occurrence in IBD outpatients.

BACKGROUND: Inflammatory bowel disease (IBD) patients are at risk of an impaired nutritional status. The impact thereof on the IBD relapse risk is clinically relevant, though sparsely investigated. AIM: The aim was to explore the association between an impaired nutritional status risk and the occurrence of disease flares in IBD outpatients participating in a longitudinal telemedicine study. METHODS: IBD outpatients were recruited from the myIBDcoach study cohort, with one year clinical follow-up. Through myIBDcoach, a telemedicine tool, patients reported on disease activity and risk of impaired nutritional status (i.e. Short Nutritional Assessment Questionnaire >1 and/or BMI < 18.5 kg/m2) every one to three months. Data was analysed by generalized estimating equation modelling. RESULTS: In total, 417 patients were included. During follow-up, 49 patients (11.8%) flared after initial clinical remission and 53 patients (12.7%) showed an increased risk of impaired nutritional status. The risk of impaired nutritional status was associated with flare occurrence (OR 2.61 (95% CI 1.02-6.69)). CONCLUSIONS: The risk of an impaired nutritional status was associated with subsequent flares in IBD outpatients. This emphasizes the importance of monitoring disease activity in IBD patients at risk of impaired nutritional status.

Novel Perceived Stress and Life Events Precede Flares of Inflammatory Bowel Disease: A Prospective 12-Month Follow-Up Study.

BACKGROUND AND AIMS: Inflammatory bowel disease [IBD] is characterized by recurrent disease flares. The impact of psychosocial wellbeing on the occurrence of flares is unclear. In this prospective study, we aimed to evaluate the association between patient-reported psychosocial wellbeing and disease flares using continuous monitoring. METHODS: Consecutive IBD patients were recruited from the myIBDcoach telemedicine study cohort. Over 12 months, participants reported on disease activity together with anxiety, depression, fatigue, perceived stress and life events every 1-3 months. Flares were defined using a combination of clinical disease activity and additional measurements. Generalized estimating equation models were used to assess associations between psychosocial wellbeing and flares over time. The influences of both the presence of psychosocial symptoms in general as well as novel psychosocial symptoms were analysed. RESULTS: In total, 417 patients were included. Forty-nine patients [11.8%] experienced a flare during the study period. The occurrence of life events in the preceding 3 months was positively associated with flares (odds ratio [OR] = 1.81; 95% confidence interval [CI] = 1.04-3.17), while the presence of anxiety, depression, fatigue and perceived stress in general was not. However, novel perceived stress [OR = 2.92; 95% CI = 1.44-5.90] was associated with flares. CONCLUSIONS: The occurrence of life events and novel perceived stress are associated with disease flares in the next 3 months, while the presence of perceived stress in general is not. These findings underline the importance of continuous personalized monitoring of IBD patients and may contribute to the prevention of disease flares.

Genomic and Expression Analyses Identify a Disease-Modifying Variant for Fibrostenotic Crohn's Disease.

Background and Aims: Crohn's disease [CD] is a chronic inflammatory disease with unpredictable behaviour. More than half of CD patients eventually develop complications such as stenosis, for which they then require endoscopic dilatation or surgery, as no anti-fibrotic drugs are currently available. We aim to identify disease-modifying genes associated with fibrostenotic CD. Methods: We performed a within-case analysis comparing 'extreme phenotypes' using the Immunochip and replication of the top single nucleotide polymorphisms [SNPs] with Agena Bioscience in two independent case-control cohorts totalling 322 cases with fibrostenotis [recurrent after surgery] and 619 cases with purely inflammatory CD. Results: Combined meta-analysis resulted in a genome-wide significant signal for SNP rs11861007 [p = 6.0910-11], located on chromosome 16, in lncRNA RP11-679B19.1, an lncRNA of unknown function, and close to exon 9 of the WWOX gene, which codes for WW domain-containing oxidoreductase. We analysed mRNA expression of TGF-ß and downstream genes in ileocecal resection material from ten patients with and without the WWOX risk allele. Patients carrying the risk allele [A] showed enhanced colonic expression of TGF-ß compared to patients homozygous for the wild-type [G] allele [p = 0.0079]. Conclusion: We have identified a variant in WWOX and in lncRNA RP11-679B19.1 as a disease-modifying genetic variant associated with recurrent fibrostenotic CD and replicated this association in an independent cohort. WWOX can potentially play a crucial role in fibrostenosis in CD, being positioned at the crossroads of inflammation and fibrosis.

Telemedicine for management of inflammatory bowel disease (myIBDcoach): a pragmatic, multicentre, randomised controlled trial.

BACKGROUND: Tight and personalised control of inflammatory bowel disease in a traditional setting is challenging because of the disease complexity, high pressure on outpatient clinics, and rising incidence. We compared the effects of self-management with a telemedicine system, which was developed for all subtypes of inflammatory bowel disease, on health-care utilisation and patient-reported quality of care versus standard care. METHODS: We did this pragmatic, randomised trial in two academic and two non-academic hospitals in the Netherlands. Outpatients aged 18-75 years with inflammatory bowel disease and without an ileoanal or ileorectal pouch anastomosis, who had internet access and Dutch proficiency, were randomly assigned (1:1) to care via a telemedicine system (myIBDcoach) that monitors and registers disease activity or standard care and followed up for 12 months. Randomisation was done with a computer-generated sequence and used the minimisation method. Participants, health-care providers, and staff who assessed outcome measures were not masked to treatment allocation. Primary outcomes were the number of outpatient visits and patient-reported quality of care (assessed by visual analogue scale score 0-10). Safety endpoints were the numbers of flares, corticosteroid courses, hospital admissions, emergency visits, and surgeries. Analyses were by intention to treat. This trial is registered with ClinicalTrials.gov, number NCT02173002. FINDINGS: Between Sept 9, 2014, and May 18, 2015, 909 patients were randomly assigned to telemedicine (n=465) or standard care (n=444). At 12 months, the mean number of outpatient visits to the gastroenterologist or nurse was significantly lower in the telemedicine group (1·55 [SD 1·50]) than in the standard care group (2·34 [1·64]; difference -0·79 [95% CI -0·98 to -0·59]; p<0·0001), as was the mean number of hospital admissions (0·05 [0·28] vs 0·10 [0·43]; difference -0·05 [-0·10 to 0·00]; p=0·046). At 12 months, both groups reported high mean patient-reported quality of care scores (8·16 [1·37] in the telemedicine group vs 8·27 [1·28] in the standard care group; difference 0·10 [-0·13 to 0·32]; p=0·411). The mean numbers of flares, corticosteroid courses, emergency visits, and surgeries did not differ between groups. INTERPRETATION: Telemedicine was safe and reduced outpatient visits and hospital admissions compared with standard care. This self-management tool might be useful for reorganising care of inflammatory bowel disease towards personalised and value-based health care. FUNDING: Maastricht University Medical Centre and Ferring.

Liver test abnormalities predict complicated disease behaviour in patients with newly diagnosed Crohn's disease.

BACKGROUNDS: In coeliac disease, the prevalence of liver test abnormalities (LTAs) is higher in patients with more severe mucosal inflammation. In Crohn's disease, prognosis is related to the severity of mucosal inflammation. AIM: The aim of this study was to investigate whether the presence of LTA predicts the occurrence of complicated disease behaviour in newly diagnosed Crohn's disease. METHODS: A retrospective cohort study was performed in patients newly diagnosed with Crohn's disease between 2002 and 2011. The complicated disease was defined as the occurrence of stricturing and/or perforating disease. LTAs were defined as a value of any of alkaline phosphatase (AP), gamma-glutamyl transpeptidase (GGT), aspartate aminotransferase (AST), or alanine aminotransferase (ALT) over the upper limit of normal. RESULTS: Three hundred eighty-three patients were included, of whom 34.1% had LTA. LTAs were mostly mild (less than two times the upper limit of normal). During the 5-year follow-up, 33.1% of patients in the group with LTA developed complicated disease behaviour compared to 14.6% in patients without LTA (p < 0.001). The presence of LTA was identified as a risk factor for complicated disease behaviour (HR 2.6, 95% confidence interval (CI) 1.5-4.2, p < 0.0001). CONCLUSIONS: In newly diagnosed Crohn's disease, the presence of LTA was an independent risk factor for the development of complicated disease behaviour.

Influence of combination therapy with immune modulators on anti-TNF trough levels and antibodies in patients with IBD.

BACKGROUND: It is important to identify factors that can reduce the incidence of immunogenicity against anti-tumor necrosis factor medication in patients with inflammatory bowel disease. The objective of our study was to evaluate the influence of cotreatment with immune modulators (IMs) on trough levels (TLs) and antidrug antibodies. METHODS: The records of all patients with inflammatory bowel disease at the Leiden University Medical Center who received either adalimumab or infliximab (IFX) in the year 2011 and/or 2012 (n = 352) were retrospectively evaluated about the assessment of TL and antibodies and use of IM. RESULTS: Two hundred seventeen patients were included (108 patients IFX; 109 patients adalimumab). Mean TL in the IFX group was higher in the combination therapy group compared with the monotherapy group, 4.6 versus 7.5 µg/mL, P = 0.04. In the adalimumab group, the difference was not significant. In patients with IFX monotherapy, the incidence of antibody formation was higher compared with patients with combination therapy (29.8% versus 5.7%, P = 0.001). IFX patients with a suboptimal dose of IM had a higher TL compared with patients who had an optimal dose, P = 0.02. The incidence of antibody formation was lower in IFX patients who immediately started with IMs compared with patients who did not (33.3% versus 66.7%, P = 0.04). CONCLUSIONS: The influence of combination therapy with IM on TL and antibodies to anti-tumor necrosis factor medication was significant for IFX-treated patients. Patients who started combination therapy immediately developed antibodies less often than patients who started later with concomitant medication.

Overeating makes the gut grow fonder; new insights in gastrointestinal satiety signaling in obesity.

PURPOSE OF REVIEW: As the prevalence of overweight and obesity increases, there is a growing need to develop effective treatment strategies in addition to bariatric surgery. Research has focused on understanding the pathophysiologic mechanisms that contribute to the occurrence and maintenance of obesity and overweight, and on how bariatric surgery is able to overcome these obstacles. In this review, new insights in the gastrointestinal regulatory mechanisms in obesity and bariatric surgery will be discussed. RECENT FINDINGS: Diet-induced obesity (DIO) leads to changes in gut peptide secretion and other gastrointestinal responses to nutrients. These changes reduce satiety signaling and therefore complicate loss of body weight. Weight loss by dietary restriction does not restore gastrointestinal responses to nutrients to normal, but alters these responses to further complicate weight loss. Only bariatric surgery is able to overcome these changes by mechanisms that are hitherto unclear but may involve altered gut peptide secretion or changes in bile acid metabolism. SUMMARY: DIO alters nutrient-induced gastrointestinal signaling in a way that facilitates further weight gain and complicates weight loss. A better understanding of these mechanisms and the way bariatric surgery can overcome these changes is crucial in developing effective treatment strategies.

Intragastric layering of lipids delays lipid absorption and increases plasma CCK but has minor effects on gastric emptying and appetite.

Intestinal intubation studies have demonstrated that lipids induce satiety, but the contribution of lipid processing by the stomach on satiety remains poorly understood. In this explorative, randomized, placebo-controlled, crossover study we tested whether delayed lipid absorption, increased cholecystokinin (CCK), decelerated gastric emptying (GE), and increased satiety can be achieved by controlling lipid distribution in the stomach. Six healthy men were intubated nasogastrically. Two treatments were performed and repeated in duplicate. In the oil-on-top treatment (OT), subjects received a fat-free liquid meal (LM, 325 ml, 145 kcal) followed by intragastric infusion of 4 g of high-oleic-acid rapeseed oil (4.6 ml, 36 kcal) labeled with 77 mg glyceryl-[(13)C]trioleate. In the emulsion treatment (EM, control), 4 g of labeled rapeseed oil was incorporated into the LM (325 ml, 181 kcal); 4.6 ml of saline was infused as a control. In OT and EM a second LM was consumed at time t = 270 min. Plasma (13)C-C18:1, CCK and satiety were measured over 480 min. GE was determined by the paracetamol absorption test. OT delayed oleic acid absorption shown by an increased lag time of absorption (EM: 37 +/- 7 min; OT: 75 +/- 10 min; P < 0.01) and time at maximum concentration (EM: 162 +/- 18 min; OT: 280 +/- 33 min; P = 0.01). OT released more CCK than EM (P = 0.03), including increased CCK after the second meal. OT accelerated initial GE until 30 min postprandial. OT showed a tendency (P = 0.06) to suppress hunger and increase satiety and fullness 120-270 min postprandially. The results demonstrate that low amounts of lipids, when separated from the aqueous phase of a meal, delay lipid absorption and increase CCK. An escalating-dose study should determine whether this could have implications for the development of weight-control foods.

Effect of fat saturation on satiety, hormone release, and food intake.

BACKGROUND: Ileal delivery of fat reduces hunger and food intake through activation of the ileal brake. Physicochemical properties of fat have been shown to affect satiety and food intake. OBJECTIVE: The objective of this study was to assess the effect of ileal fat emulsions with differing degrees of fatty acid saturation on satiety, food intake, and gut peptides (cholecystokinin and peptide YY). We hypothesized that long-chain triacylglycerols with diunsaturated fatty acids would increase satiety and reduce energy intake compared with long-chain triacylglycerols with monounsaturated or saturated fatty acids. DESIGN: We performed a double-blind, randomized, crossover study in which 15 healthy subjects [mean age: 24 y; mean body mass index (in kg/m(2)): 22] were intubated with a naso-ileal catheter and participated in 4 experiments performed in random order on 4 consecutive days. After consumption of a liquid meal, subjects received a fat or control infusion in the ileum. Fat emulsions consisted of 6 g of 18:0 (shea oil; mainly 18:0), 18:1 (canola oil; mainly 18:1), or 18:2 (safflower oil; mainly 18:2) oils. Food intake was measured during an ad libitum lunch. Satiety questionnaires (visual analog scale) and blood samples were collected at regular intervals. RESULTS: Compared with the control, only 18:2 and 18:1 significantly increased fullness and reduced hunger. No effect on food intake was observed. 18:1 and 18:2 increased cholecystokinin secretion significantly compared with the control. Fatty acid saturation did not affect peptide YY secretion. CONCLUSIONS: When infused into the ileum, triacylglycerols with unsaturated fatty acids increase satiety, whereas triacylglycerols with saturated fatty acids does not. This trial was registered with the Dutch Trial Register as: ISRCTN51742545.