Shifts in immune responses of an invasive alien species: A test of the evolution of increased competitive ability hypothesis using American Eastern gray squirrels in Italy.

Based on the Evolution of Increased Competitive Ability (EICA) hypothesis, a reduced investment in immunity, consequent to parasite loss, could partly explain the success of invasive alien species. We investigated variation in parasite load and immune responses of alien Eastern gray squirrels (Sciurus carolinensis) along the invasion wave of an expanding population. We first verified by fecal analyses that 1) parasite abundance decreased moving from the core towards the invasion front. Next, we used multiple measures of immunity to investigate whether, in response to the lower parasite pressure, individuals at the invasion front 2) dampened their costly inflammatory response, and 3) increased their investment in less expensive acquired immunity. We first explored variation in hematological variables related either to the inflammatory or the acquired response. On a subset of individuals, we carried out ex vivo cell cultures to analyse the basal expression of MHC class II genes and the expression of TNF-α genes in response to an immune challenge. Platelet counts and TNF-α expression suggested higher inflammation in individuals living at the invasion core, whereas parameters associated with an acquired response (lymphocyte counts and MHC II expression by spleen cells), conversely, were higher in squirrels at the front. Overall, our results suggest a shift between different immune strategies along the invasion wave, supporting a reduced investment in costly inflammatory responses and an increased investment in acquired immunity in individuals at the expanding edge of the range, which are subjected to high selective pressures for dispersal and reproduction.

Clinical outcomes in pediatric inflammatory bowel disease patients: a systematic review of prospective studies.

BACKGROUND AND AIM: We studied response and remission rates in children and adolescents with inflammatory bowel disease whose real-world data were collected prospectively. METHODS: A systematic literature search was performed in MEDLINE, Embase, and the Improve Care Now registry from inception until March 17, 2022. Inclusion criteria were prospective studies with patients < 18 years at diagnosis (M0) and minimum follow-up of 1 year (M12) mentioning disease phenotype and disease activity. Exclusion criteria were (i) reporting disease activity only at diagnosis, (ii) retrospective studies, and (iii) outcome limited to steroid-free remission. The Preferred Reporting Items for Systematic Reviews and Meta-Analyses Protocols guidelines and the Newcastle-Ottawa scale were applied. Proportions between groups were compared using a chi-square test (α = 0.05). RESULTS: The search yielded 394 records and 7 inclusions with a sample size ranging from 33 to 390 patients (total population: 888) and a median follow-up of 1-5 years. Proportions of disease activity differed between M0 and M12 (P < 0.0001) with more inactive (χ2  = 5.5) and less moderate-to-severe disease (χ2  = 23) at M12. Interestingly, disease activity after 1 year did not differ globally (P = 0.53). Proportions of disease activity in Crohn's disease only and limited to Belgium significantly differed from baseline after 5 years (P < 0.0001 for evolution) but not between 1- and 5-year follow-up (P = 0.94). CONCLUSIONS: The few available prospective cohorts reported a significant decrease in disease activity after 1 year, with no global differences. Proportions of disease activity did not differ between 1- and 5-year follow-up in the Belgian Crohn's disease cohort, suggesting stable disease activity.

Effect of sleeve gastrectomy and Roux-en-Y gastric bypass on gastrointestinal physiology.

BACKGROUND: Knowledge regarding the gastrointestinal physiology after sleeve gastrectomy and Roux-en-Y gastric bypass is urgently needed to understand, prevent and treat the nutritional and pharmacological complications of bariatric surgery. AIM: To investigate the effect of sleeve gastrectomy and Roux-en-Y gastric bypass on gastrointestinal motility (e.g., transit and pressure), pH, and intestinal bile acid concentration. MATERIAL AND METHODS: An exploratory cross-sectional study was performed in six participants living with obesity, six participants who underwent sleeve gastrectomy, and six participants who underwent Roux-en-Y gastric bypass. During the first visit, a wireless motility capsule (SmartPill©) was ingested after an overnight fast to measure gastrointestinal transit, pH, and pressure. During the second visit, a gastric emptying scintigraphy test of a nutritional drink labeled with 99mTc-colloid by a dual-head SPECT gamma camera was performed to measure gastric emptying half-time (GET1/2). During the third visit, two customized multiple lumen aspiration catheters were positioned to collect fasting and postprandial intestinal fluids to measure bile acid concentration. RESULTS: Immediate pouch emptying (P = 0.0007) and a trend for faster GET1/2 (P = 0.09) were observed in both bariatric groups. There was a tendency for a shorter orocecal transit in participants with sleeve gastrectomy and Roux-en-Y gastric bypass (P = 0.08). The orocecal segment was characterized by a higher 25th percentile pH (P = 0.004) and a trend for a higher median pH in both bariatric groups (P = 0.07). Fasting total bile acid concentration was 7.5-fold higher in the common limb after Roux-en-Y gastric bypass (P < 0.0001) and 3.5-fold higher in the jejunum after sleeve gastrectomy (P = 0.009) compared to obesity. Postprandial bile acid concentration was 3-fold higher in the jejunum after sleeve gastrectomy (P = 0.0004) and 6.5-fold higher in the common limb after Roux-en-Y gastric bypass (P < 0.0001) compared to obesity. CONCLUSION: The anatomical alterations of sleeve gastrectomy and Roux-en-Y gastric bypass have an important impact on gastrointestinal physiology. This data confirms changes in transit and pH and provides the first evidence for altered intraluminal bile acid concentration.

Potential importance of early treatment of SARS-CoV-2 infection in intestinal transplant patient: A case report.

BACKGROUND: Predispositions for severe coronavirus disease 2019 (COVID-19) are age, immunosuppression, and co-morbidity. High levels of maintenance immunosuppression render intestinal transplant (ITx) patients vulnerable for severe COVID-19. COVID-19 also provokes several gastroenterological pathologies which have not been discussed in ITx, so far. CASE SUMMARY: During the second European COVID-19 wave in November 2020, an ITx recipient was admitted to the hospital because of electrolyte disturbances due to dehydration. Immunosuppression consisted of tacrolimus, azathioprine, and low-dose corticosteroids. During hospitalization, she tested positive on screening COVID-19 nasopharyngeal polymerase chain reaction swab, while her initial test was negative. She was initially asymptomatic and had normal inflammatory markers. Tacrolimus levels were slightly raised, as Azathioprine was temporarily halted. Due to elevated D-dimers at that time, prophylactic low-molecular weight heparin was started. Seven days after the positive test, dyspnea, anosmia, and C-reactive protein increase (25 mg/L) were noted. Remdesivir was administered during 5 d in total. High stomal output was noted in two consecutive days and several days thereafter. To exclude infection or rejection, an ileoscopy and biopsy were performed and excluded these. Four weeks later, she was discharged from the hospital and remains in good health since then. CONCLUSION: Early eradication of severe acute respiratory syndrome coronavirus 2 in ITx recipients may be warranted to prevent acute rejection provocation by it.

Estrogens Play a Critical Role in Stress-Related Gastrointestinal Dysfunction in a Spontaneous Model of Disorders of Gut-Brain Interaction.

BACKGROUND: Disorders of the gut-brain interaction (DGBI), such as irritable bowel syndrome and functional dyspepsia, are more prevalent in women than in men, with a ratio of 2:1. Furthermore, stressful life events have been reported as one of the triggers for symptoms in DGBI patients. METHODS: Here, we studied the effect of an early-life stressor (maternal separation (MS)) on jejunal and colonic alterations, including colonic sensitivity and immune cells infiltration and activation in a validated spontaneous model of DGBI (BBDP-N), and investigated the involvement of ß-estradiol on stress-worsened intestinal alterations. RESULTS: We found that maternal separation exacerbated colonic sensitivity and mast cell and eosinophil infiltration and activation in females only. Ovariectomy partially rescued the stress phenotype by decreasing colonic sensitivity, which was restored by ß-estradiol injections and did not impact immune cells infiltration and activation. Stressed males exposed to ß-estradiol demonstrated similar intestinal alterations as MS females. CONCLUSION: Estrogen plays a direct critical role in colonic hypersensitivity in a spontaneous animal model of DGBI, while for immune activation, estrogen seems to be involved in the first step of their recruitment and activation. Our data point towards a complex interaction between stress and ß-estradiol in DGBI.

Enterohormone therapy for short bowel syndrome.

PURPOSE OF REVIEW: Short bowel syndrome (SBS) patients are at risk to develop intestinal failure when the decreased absorption of macronutrients, water, and electrolytes necessitates parenteral support for survival. The adverse effects of SBS and parenteral support negatively affect the quality of life (QoL) of SBS-intestinal failure patients. However, spontaneous intestinal adaptation along with disease-modifying therapies allow reducing parenteral support, thereby improving QoL. RECENT FINDINGS: During the first years following extensive surgery, spontaneous structural and functional intestinal changes take place which stimulate a more efficient nutrient and fluid absorption in the remaining bowel. Given their potential role in the ileal braking mechanism, enterohormones, such as glucagon-like peptide (GLP)-2, GLP-1, and peptide YY (PYY), promote an accelerated adaptation or hyperadaptation. While the exact role of GLP-1 and PYY in SBS is still being explored, GLP-2 analogs have clearly shown to be effective in improving outcome in SBS. SUMMARY: Whereas spontaneous intestinal adaptation improves the nutritional status of SBS patients to a certain extent, GLP-2 analogs can further decrease parenteral support needs through hyperadaptation. There are, however, other promising candidates on the horizon that - alone or in combination - could possibly establish additional disease-modifying effects.

Efficacy and safety of spore-forming probiotics in the treatment of functional dyspepsia: a pilot randomised, double-blind, placebo-controlled trial.

BACKGROUND: Current treatments for functional dyspepsia have limited efficacy or present safety issues. We aimed to assess spore-forming probiotics in functional dyspepsia as monotherapy or add-on therapy to long-term treatment with proton-pump inhibitors. METHODS: In this single-centre, randomised, double-blind, placebo-controlled pilot trial that took place at University Hospitals Leuven (Leuven, Belgium), adult patients (≥18 years) with functional dyspepsia (as defined by Rome IV criteria, on proton-pump inhibitors or off proton-pump inhibitors) were randomly assigned (1:1) via computer-generated blocked lists, stratified by proton-pump inhibitor status, to receive 8 weeks of treatment with probiotics (Bacillus coagulans MY01 and Bacillus subtilis MY02, 2·5 × 109 colony-forming units per capsule) or placebo consumed twice per day, followed by an open-label extension phase of 8 weeks. Individuals with a history of abdominal surgery, diabetes, coeliac or inflammatory bowel disease, active psychiatric conditions, and use of immunosuppressant drugs, antibiotics, or probiotics in the past 3 months were excluded. All patients and on-site study personnel were masked to treatment allocation in the first 8 weeks. Symptoms, immune activation, and faecal microbiota were assessed and recorded. The primary endpoint was a decrease of at least 0·7 in the postprandial distress syndrome (PDS) score of the Leuven Postprandial Distress Scale in patients with a baseline PDS score of 1 or greater (at least mild symptoms), assessed in the intention-to-treat population. This study is registered with ClinicalTrials.gov, NCT04030780. FINDINGS: Between June 3, 2019, and March 11, 2020, of 93 individuals assessed for eligibility, we included 68 patients with functional dyspepsia (51 [75%] women, mean age 40·1 years [SD 14·4], 34 [50%] on proton-pump inhibitors). We randomly assigned 32 participants to probiotics and 36 to placebo. The proportion of clinical responders was higher with probiotics (12 [48%] of 25) than placebo (six [20%] of 30; relative risk 1·95 [95% CI 1·07-4·11]; p=0·028). The number of patients with adverse events was similar with probiotics (five [16%] of 32) and placebo (12 [33%] of 36). Two serious adverse events occurring during the open-label phase (appendicitis and syncope in two separate patients) were assessed as unlikely to be related to the study product. INTERPRETATION: In this exploratory study, B coagulans MY01 and B subtilis MY02 were efficacious and safe in the treatment of functional dyspepsia. Participants had potentially beneficial immune and microbial changes, which could provide insights into possible underlying mechanisms as future predictors or treatment targets. FUNDING: MY HEALTH.

United European Gastroenterology (UEG) and European Society for Neurogastroenterology and Motility (ESNM) consensus on gastroparesis.

BACKGROUND: Gastroparesis is a condition characterized by epigastric symptoms and delayed gastric emptying (GE) rate in the absence of any mechanical obstruction. The condition is challenging in clinical practice by the lack of guidance concerning diagnosis and management of gastroparesis. METHODS: A Delphi consensus was undertaken by 40 experts from 19 European countries who conducted a literature summary and voting process on 89 statements. Quality of evidence was evaluated using grading of recommendations assessment, development, and evaluation criteria. Consensus (defined as ≥80% agreement) was reached for 25 statements. RESULTS: The European consensus defined gastroparesis as the presence of symptoms associated with delayed GE in the absence of mechanical obstruction. Nausea and vomiting were identified as cardinal symptoms, with often coexisting postprandial distress syndrome symptoms of dyspepsia. The true epidemiology of gastroparesis is not known in detail, but diabetes, gastric surgery, certain neurological and connective tissue diseases, and the use of certain drugs recognized as risk factors. While the panel agreed that severely impaired gastric motor function is present in these patients, there was no consensus on underlying pathophysiology. The panel agreed that an upper endoscopy and a GE test are required for diagnosis. Only dietary therapy, dopamine-2 antagonists and 5-HT4 receptor agonists were considered appropriate therapies, in addition to nutritional support in case of severe weight loss. No consensus was reached on the use of proton pump inhibitors, other classes of antiemetics or prokinetics, neuromodulators, complimentary, psychological, or more invasive therapies. Finally, there was consensus that gastroparesis adversely impacts on quality of life and healthcare costs and that the long-term prognosis of gastroparesis depends on the cause. CONCLUSIONS AND INFERENCES: A multinational group of European experts summarized the current state of consensus on definition, symptom characteristics, pathophysiology, diagnosis, and management of gastroparesis.

United European Gastroenterology (UEG) and European Society for Neurogastroenterology and Motility (ESNM) consensus on gastroparesis.

BACKGROUND: Gastroparesis is a condition characterized by epigastric symptoms and delayed gastric emptying (GE) rate in the absence of any mechanical obstruction. The condition is challenging in clinical practice by the lack of guidance concerning diagnosis and management of gastroparesis. METHODS: A Delphi consensus was undertaken by 40 experts from 19 European countries who conducted a literature summary and voting process on 89 statements. Quality of evidence was evaluated using grading of recommendations assessment, development, and evaluation criteria. Consensus (defined as ≥80% agreement) was reached for 25 statements. RESULTS: The European consensus defined gastroparesis as the presence of symptoms associated with delayed GE in the absence of mechanical obstruction. Nausea and vomiting were identified as cardinal symptoms, with often coexisting postprandial distress syndrome symptoms of dyspepsia. The true epidemiology of gastroparesis is not known in detail, but diabetes, gastric surgery, certain neurological and connective tissue diseases, and the use of certain drugs recognized as risk factors. While the panel agreed that severely impaired gastric motor function is present in these patients, there was no consensus on underlying pathophysiology. The panel agreed that an upper endoscopy and a GE test are required for diagnosis. Only dietary therapy, dopamine-2 antagonists and 5-HT4 receptor agonists were considered appropriate therapies, in addition to nutritional support in case of severe weight loss. No consensus was reached on the use of proton pump inhibitors, other classes of antiemetics or prokinetics, neuromodulators, complimentary, psychological, or more invasive therapies. Finally, there was consensus that gastroparesis adversely impacts on quality of life and healthcare costs and that the long-term prognosis of gastroparesis depends on the cause. CONCLUSIONS AND INFERENCES: A multinational group of European experts summarized the current state of consensus on definition, symptom characteristics, pathophysiology, diagnosis, and management of gastroparesis.

United European Gastroenterology (UEG) and European Society for Neurogastroenterology and Motility (ESNM) consensus on functional dyspepsia.

BACKGROUND: Functional dyspepsia (FD) is one of the most common conditions in clinical practice. In spite of its prevalence, FD is associated with major uncertainties in terms of its definition, underlying pathophysiology, diagnosis, treatment, and prognosis. METHODS: A Delphi consensus was initiated with 41 experts from 22 European countries who conducted a literature summary and voting process on 87 statements. Quality of evidence was evaluated using the grading of recommendations, assessment, development, and evaluation (GRADE) criteria. Consensus (defined as >80% agreement) was reached for 36 statements. RESULTS: The panel agreed with the definition in terms of its cardinal symptoms (early satiation, postprandial fullness, epigastric pain, and epigastric burning), its subdivision into epigastric pain syndrome and postprandial distress syndrome, and the presence of accessory symptoms (upper abdominal bloating, nausea, belching), and overlapping conditions. Also, well accepted are the female predominance of FD, its impact on quality of life and health costs, and acute gastrointestinal infections, and anxiety as risk factors. In terms of pathophysiological mechanisms, the consensus supports a role for impaired gastric accommodation, delayed gastric emptying, hypersensitivity to gastric distention, Helicobacter pylori infection, and altered central processing of signals from the gastroduodenal region. There is consensus that endoscopy is mandatory for establishing a firm diagnosis of FD, but that in primary care, patients without alarm symptoms or risk factors can be managed without endoscopy. There is consensus that H. pylori status should be determined in every patient with dyspeptic symptoms and H. pylori positive patients should receive eradication therapy. Also, proton pump inhibitor therapy is considered an effective therapy for FD, but no other treatment approach reached a consensus. The long-term prognosis and life expectancy are favorable. CONCLUSIONS AND INFERENCES: A multinational group of European experts summarized the current state of consensus on the definition, diagnosis and management of FD.

Health Literacy and Quality of Life in Young Adults From The Belgian Crohn's Disease Registry Compared to Type 1 Diabetes Mellitus.

Background and Aims: The management of chronic inflammatory bowel diseases in youth is challenging. We aimed to determine health literacy (HL), quality of life (QoL) and clinical outcomes in young adults from the BELgian CROhn's disease registry (BELCRO) in comparison to type 1 diabetes mellitus (DM) as a control. Methods: In this prospective and observational study, young adults with Crohn's disease (CD) diagnosed < 18 years and with > 5 years disease duration and a comparable group of patients with DM completed validated HL, QoL and work productivity and activity impairment questionnaires (HLS-EU-Q16, EQ-5D-5L and WPAI). HL was scored as sufficient (13-16), problematic (9-12) or inadequate (0-8). QoL was dichotomized into "no problems" (EQ-5D level 1) or "problems" (EQ-5D levels 2 to 5). Non-parametric (Mann-Whitney U) analyses and Spearman correlations were performed. Results: A total of 52 CD (median [IQR] age of 25.0 [23.8-27.0], 64% male) and 50 DM (age 20.0 [19.0-22.0], 50% male) patients were included. HL was 14.0 [11.0-16.0] for CD and 14.0 [11.3-14.8] for DM (p = 0.6) with similar proportions of sufficient (60 vs. 68%, p = 0.4), problematic (34 vs. 26%, p = 0.3) and inadequate HL (both 6%, p = 1). Although QoL was comparable for CD and DM (77.0 [68.8-82.0] vs. 75.0 [65.0-80.0] %, p =0.4), CD had a trend for higher pain/discomfort (50 vs. 32%, p = 0.06). HL and QoL correlated in CD (r = 0.6, p < 0.001) and DM patients (r = 0.6, p < 0.001). Fewer CD patients with recent hospitalization/surgery had sufficient HL (31 vs. 69%, p = 0.01) and had lower QoL (70.0 [60.0-77.0] vs. 80.0 [70.0-85.0], p = 0.04) compared to those without. Conclusions: Selected young Belgian adults suffering from CD for >5 years have similar and sufficient HL compared to DM patients. However, CD patients requiring hospitalization/surgery have lower HL, which indicates the need for targeted educational programs.

Duodenal acidification induces gastric relaxation and alters epithelial barrier function by a mast cell independent mechanism.

Duodenal hyperpermeability and low-grade inflammation in functional dyspepsia is potentially related to duodenal acid exposure. We aimed to evaluate in healthy volunteers the involvement of mast cell activation on the duodenogastric reflex and epithelial integrity during duodenal acidification. This study consisted of 2 parts: (1) Duodenal infusion of acid or saline during thirty minutes in a randomized, double-blind cross-over manner with measurement of intragastric pressure (IGP) using high resolution manometry and collection of duodenal biopsies to measure epithelial barrier function and the expression of cell-to-cell adhesion proteins. Mast cells and eosinophils were counted and activation and degranulation status were assessed. (2) Oral treatment with placebo or mast cell stabilizer disodiumcromoglycate (DSCG) prior to duodenal perfusion with acid, followed by the procedures described above. Compared with saline, acidification resulted in lower IGP (P < 0.01), increased duodenal permeability (P < 0.01) and lower protein expression of claudin-3 (P < 0.001). Protein expression of tryptase (P < 0.001) was increased after acid perfusion. Nevertheless, an ultrastructural examination did not reveal degranulation of mast cells. DSCG did not modify the drop in IGP and barrier dysfunction induced by acid. Duodenal acidification activates an inhibitory duodenogastric motor reflex and, impairs epithelial integrity in healthy volunteers. However, these acid mediated effects occur independently from mast cell activation.

Efficacy and safety of lanreotide in postoperative dumping syndrome: A Phase II randomised and placebo-controlled study.

Background: Data on the efficacy and safety of the long-acting somatostatin analogue lanreotide (LAN) for postoperative dumping syndrome are lacking. Objective: We performed a double-blind, randomised and placebo-controlled crossover study of LAN Autogel® 90 mg in postoperative dumping. Methods: Adults with a positive prolonged oral glucose tolerance test or spontaneous hypoglycaemia and total dumping score (DS) ≥ 10 despite dietary measures were treated with three monthly injections of LAN or placebo in a randomised crossover fashion with an eight-week wash-out period. Primary outcome was the effect of LAN on total DS versus placebo. Secondary outcomes were the effect on early and late DS, treatment assessment, quality of life and safety. Results: Of 24 included patients (66.7% female; age 49.1 ± 2.1 years), 12 were randomised to LAN first. Pooled DS after three injections were lower compared to baseline after LAN (median=14 (interquartile range (IQR) 11.5-23) vs. median = 22 (IQR 16-27); p = 0.03) but not placebo (median = 20 (IQR 15-27) vs. median = 23 (IQR 13-29); p = 0.15). Improvement of early (median = 7.5 (IQR 4.5-13) vs. median = 12 (IQR 9-16); p = 0.03) but not late (median = 7 (IQR 6-10.3) vs. median = 9 (IQR 6-13); p = 0.26) DS was seen. Overall treatment assessment correlated with change in DS (r = -0.69, p = 0.004). Symptom improvement was not associated with changes in quality of life. Of the 81 reported adverse events, 44 occurred on LAN compared to 37 on placebo (p > 0.05), with seven serious adverse events on LAN. Conclusions: LAN is effective for treating early postoperative dumping symptoms, although side effects are common and quality of life is not significantly affected.

Applications of peptide hormone ligands for the treatment of dumping and short bowel syndrome.

Dumping syndrome is a common and debilitating complication of upper gastrointestinal surgery. Accelerated gastric emptying and dysregulated secretion of gastrointestinal (GI) hormones are involved in its pathophysiology. Pasireotide, a novel somatostatin analogue, improved dumping in a phase-2 study. Preliminary data suggest that the glucagon-like peptide-1 (GLP-1) analogue liraglutide can also improve dumping. Short bowel syndrome is the most common cause of intestinal failure and involves not only a loss of mucosal absorptive area but also hypersecretion and accelerated transit. GLP-2 is the best studied hormone involved in intestinal adaptation. An increasing body of evidence demonstrates that the GLP-2 analogue teduglutide reduces parenteral support needs. New GLP-2 analogues and analogues of other GI hormones such as liraglutide are being investigated as promising treatments in short bowel syndrome.

Long-term Outcomes with Anti-TNF Therapy and Accelerated Step-up in the Prospective Pediatric Belgian Crohn's Disease Registry (BELCRO).

BACKGROUND: Accelerated step-up or anti-tumor necrosis factor (TNF) before first remission is currently not recommended in pediatric Crohn's disease. METHODS: Five-year follow-up data from a prospective observational cohort of children diagnosed with Crohn's disease in Belgium were analyzed. Disease severity was scored as inactive, mild, or moderate to severe. Remission or inactive disease was defined as sustained if lasting ≥2 years. Univariate analyses were performed between anti-TNF-exposed versus naive patients and anti-TNF before versus after first remission and correlations assessed with primary outcomes average disease severity and sustained remission. RESULTS: A total of 91 patients (median [IQR] age 12.7 [10.9-14.8] yrs, 53% male) were included. Disease location was 12% L1, 23% L2, and 64% L3 with 76% upper gastrointestinal and 30% perianal involvement. Disease severity was 25% mild and 75% moderate to severe. Of 66 (73%) anti-TNF-exposed patients, 34 (52%) had accelerated step-up. Anti-TNF use was associated with age (13.1 [11.5-15.2] versus 11.8 [8.7-13.8] yrs; P < 0.05), L2 (29% versus 8%; P = 0.04), and average disease severity (1.7 [1.4-1.9] versus 1.4 [1.3-1.6]; P < 0.001). Duration of anti-TNF correlated with average disease severity (r = 0.32, P = 0.002). Accelerated step-up was also associated with age (13.3 [12.1-15.9] versus 12.5 [10.2-14.1]; P = 0.02) and average disease severity (1.8 [1.6-1.9] versus 1.6 [1.3-1.8]; P = 0.002). Duration of sustained remission was similar in all patients, and no serious infections, cancer, or deaths were reported. CONCLUSIONS: Anti-TNF therapy and accelerated step-up in older patients with more severe disease leads to beneficial long-term outcomes.

Incidence of renal cell carcinoma in inflammatory bowel disease patients with and without anti-TNF treatment.

OBJECTIVE: We aimed to study the risk of renal cell carcinoma (RCC) with anti-tumor necrosis factor (anti-TNF) therapy in inflammatory bowel disease (IBD) and rheumatic diseases (RD) and calculate standardized incidence ratios (SIRs) in IBD. MATERIALS AND METHODS: This was a retrospective case-control and cohort study spanning 25 years, including IBD and RD patients with a diagnosis of RCC (1990-2014) identified through the electronic database of a tertiary referral center. RESULTS: RCC was confirmed in seven anti-TNF-exposed (TNF+) and 21 anti-TNF-naive (TNF-) IBD and one TNF+ and 26 TNF- RD patients. In IBD-RCC, younger age at RCC diagnosis [median (interquartile range) 46 (42-58) vs. 63 (52-75) years; P=0.02], immunosuppressive therapy (100 vs. 24%; P<0.0004), partial nephrectomy (86 vs. 33%; P=0.02), and surgery less than 1 month after diagnosis of RCC (71 vs. 14%; P=0.004) were associated with anti-TNF. Compared with IBD, RD patients were older at RCC diagnosis [70 (60-77) vs. 59 (47-69) years; P=0.02] with less nephron-sparing surgery (26 vs. 54%; P=0.04) and more symptomatic (44 vs. 14%; P=0.02) and advanced tumors (30 vs. 7%; P=0.04). SIRs in IBD-RCC TNF- and TNF+ were 5.4 (95% confidence interval 2.9-9.2) and 7.1 (2.3-16.5) in male patients and 8.5 (3.7-16.8) and 4.8 (0.6-17.3) in female patients, respectively. The risk for RCC associated with anti-TNF in IBD was 0.8 (0.3-2.5) in men and 1.4 (0.2-5.5) in women. CONCLUSION: The favorable patient and tumor profiles in IBD with anti-TNF may suggest incidentally discovered RCC on abdominal imaging. SIRs for IBD-RCC were not increased after anti-TNF exposure.

Cow's Milk Allergy Prescribing Is Influenced by Regional and National Guidance.

OBJECTIVES: Cow's milk allergy (CMA) is the most common food allergy in children with many clinical manifestations, leading to misdiagnoses such as gastro-oesophageal reflux, infantile colic, and lactose intolerance with inappropriate prescribing. We aimed to determine the impact of infant feeding guidelines on CMA prescribing in UK primary care using a simple and inexpensive training package. METHODS: Prospectively collected data of infant feeding prescriptions in Northern Ireland from June 2012 to March 2014 were analysed with the intervention period between November 2012 and March 2013. A comparison was made between hypoallergenic formulae, appropriate for CMA, versus alternative prescriptions including antiregurgitation and colic products, lactose-free and partially hydrolysed milks, or infant Gaviscon. RESULTS: Comparing pre- and postintervention period, the total quantity of hypoallergenic formulae increased by 63.2% and alternative prescriptions decreased by 44.6% (P < 0.001). The total amount of all prescribed products decreased by 41.0% (P < 0.001). During the study period, the proportion of recommended CMA treatment increased from 3.4% before training to 9.8% in the short- and long-term follow-up (P < 0.001). The overall increase was £33,508 per year or £95.5 per general practitioner's surgery. CONCLUSIONS: We present the first study evaluating the impact of infant feeding guidelines on CMA prescribing in UK primary care. Practical advice and teaching of health professionals allowed for effective implementation of regional and national guidelines, with a significant impact on prescription patterns. This study shows promising results for prospective research on a national scale, including socioeconomical impact and cost-effectiveness.