Gut metabolome and microbiota signatures predict response to treatment with exclusive enteral nutrition in a prospective study in children with active Crohn's disease.

BACKGROUND: Predicting response to exclusive enteral nutrition (EEN) in active Crohn's disease (CD) could lead to therapy personalization and pretreatment optimization. OBJECTIVES: This study aimed to explore the ability of pretreatment parameters to predict fecal calprotectin (FCal) levels at EEN completion in a prospective study in children with CD. METHODS: In children with active CD, clinical parameters, dietary intake, cytokines, inflammation-related blood proteomics, and diet-related metabolites, metabolomics and microbiota in feces, were measured before initiation of 8 wk of EEN. Prediction of FCal levels at EEN completion was performed using machine learning. Data are presented with medians (IQR). RESULTS: Of 37 patients recruited, 15 responded (FCal < 250 µg/g) to EEN (responders) and 22 did not (nonresponders). Clinical and immunological parameters were not associated with response to EEN. Responders had lesser (µmol/g) butyrate [responders: 13.2 (8.63-18.4) compared with nonresponders: 22.3 (12.0-32.0); P = 0.03], acetate [responders: 49.9 (46.4-68.4) compared with nonresponders: 70.4 (57.0-95.5); P = 0.027], phenylacetate [responders: 0.175 (0.013-0.611) compared with nonresponders: 0.943 (0.438-1.35); P = 0.021], and a higher microbiota richness [315 (269-347) compared with nonresponders: 243 (205-297); P = 0.015] in feces than nonresponders. Responders consumed (portions/1000 kcal/d) more confectionery products [responders: 0.55 (0.38-0.72) compared with nonresponders: 0.19 (0.01-0.38); P = 0.045]. A multicomponent model using fecal parameters, dietary data, and clinical and immunological parameters predicted response to EEN with 78% accuracy (sensitivity: 80%; specificity: 77%; positive predictive value: 71%; negative predictive value: 85%). Higher taxon abundance from Ruminococcaceae, Lachnospiraceae, and Bacteroides and phenylacetate, butyrate, and acetate were the most influential variables in predicting lack of response to EEN. CONCLUSIONS: We identify microbial signals and diet-related metabolites in feces, which could comprise targets for pretreatment optimization and personalized nutritional therapy in pediatric CD.

YouTube as a Source of Information for Food, Diet-Related Items, and Advisory Comments for the Management of Inflammatory Bowel Disease.

BACKGROUND: Patients with inflammatory bowel disease (IBD) often use the Internet to seek information beyond that received from healthcare professionals. This study assessed the perceptions of YouTube presenters on the role of diet in the management of IBD. METHODS: Videos discussing dietary aspects (food, diet-related items, and advisory comments [FODRIACs]) in the management of IBD were included. The perceptions of presenters toward each FODRIAC were labeled as positive, negative, or neutral/intermediate, and FODRIACs were classified according to their underlying role in the management of IBD (eg, symptom management, gut inflammation). Subgroup analysis was performed by type of video presenter (patients vs healthcare professionals), type of IBD (Crohn's disease vs ulcerative colitis), and reporting of scientific evidence supporting presenters' perceptions. RESULTS: We identified 122 FODRIACs within 160 videos. Patient videos received a higher number of likes (median 85 [interquartile range, 35-156]) than healthcare professional videos (median 44 [interquartile range, 16-1440]) (P = .01). Scientific evidence was cited in 2 (3%) of 76 patient videos compared with 25 (35%) of 71 healthcare professional videos (P < .001). Positive perceptions were expressed about avocadoes, salmon, bananas, white bread, and rice, whereas negative perceptions were reported for processed, high-fat and high-sugar foods and carbonated drinks. Fewer negative perceptions were expressed in videos supported by scientific evidence than in videos that lacked evidence (scientific: 4 positive, 0 negative vs nonscientific: 7 positive, 20 negative; P = .01). CONCLUSIONS: We have identified FODRIACs proposed as beneficial or detrimental in the management of IBD. The effect this information has on dietary practice as patients with IBD self-manage their condition needs further exploration.

Take-Home Messages from 20 Years of Progress in Dietary Therapy of Inflammatory Bowel Disease.

BACKGROUND: A significant body of literature has interrogated the critical role of diet in the development and management of inflammatory bowel disease (IBD). SUMMARY: This review provides a summary and critical appraisal of the literature in this area, focussing on four distinct themes: nutritional epidemiology, animal and in vitro experiments, enteral nutrition, and food-based dietary therapies. KEY MESSAGES: Nutritional epidemiology and data from experiments in animals indicate that a western-type diet pattern is associated with increased risk of IBD onset. However, these findings have not been consistently replicated in the dietary management of IBD. Exclusive enteral nutrition (EEN) is the only dietary therapy with reproducible evidence of efficacy in the management of active Crohn's disease (CD). Use of EEN may also be useful for improving perioperative outcomes in CD, and as an adjuvant therapy to biologic therapy. Several dietary therapies for CD and ulcerative colitis have been proposed in the literature, but replication in well-controlled studies is needed before their routine use enters the clinical setting. Precision nutritional therapy might be an attractive therapeutic paradigm in a heterogenous disease like IBD. However, no recommendations for personalised dietary therapy can currently be made, and it is imperative we unravel the complex interplay between diet and gut inflammation before we are able to do so. Undoubtedly, diet is of critical importance in the development and management of IBD. However, the exact mechanism by which diet causes gut inflammation is still elusive, and dietary guidance is difficult to formulate.

Improved clinical outcomes with early anti-tumour necrosis factor alpha therapy in children with newly diagnosed Crohn's disease: real world data from the international prospective PIBD-SETQuality inception cohort study.

BACKGROUND & AIMS: Treatment guidelines for paediatric Crohn's disease (CD) suggest early use of anti-tumour necrosis factor alpha (anti-TNF) in high-risk individuals. The aim is to evaluate the effect of early anti-TNF in a real-world cohort. METHODS: Children with newly-diagnosed CD were prospectively recruited at 28 participating sites of the international observational PIBD-SETQuality study. Outcomes were compared at 3 months, 1 and 2 years between patients receiving early anti-TNF (<90 days after diagnosis) and those not receiving early anti-TNF. Outcomes included sustained steroid-free remission (SSFR) without treatment intensification (specified as SSFR*) and sustained steroid-free mild/inactive disease without treatment intensification (specified as SSFMI*). Penalised logistic regression model-based standardisation was applied to estimate the relative risks (RR) of early therapy on outcomes. RRs were estimated for high-risk and low-risk patients based on presence of predictors of poor outcome (POPOs) and disease activity at diagnosis. RESULTS: In total, 331 children (median age 13.9 years [IQR 12.2 - 15.3]) were enrolled, with 135 (41%) receiving early anti-TNF. At 1 year, patients on early anti-TNF had higher rates of SSFR* (30% vs. 14%, p<0.001) and SSFMI* (69% vs. 33%, p<0.001), with RRs of 2.95 (95%CI 1.63-5.36) and 4.67 (95%CI 2.46-8.87) respectively. At 1 year, the RRs for SSFMI* were higher, and statistically significant in high-risk patients, i.e. those with moderate/severe disease compared to mild/inactive disease at diagnosis (5.50 [95%CI 2.51-12.05]) vs. 2.91 [95%CI 0.92-9.11]), and those with any POPO compared to no POPO (5.05 [95%CI 2.45-10.43] vs. 3.41 [95%CI 0.54-21.7]). CONCLUSION: In this cohort of children with newly-diagnosed CD, early anti-TNF demonstrated superior effectiveness in high-risk patients.

The inexorable increase of biologic exposure in paediatric inflammatory bowel disease: a Scottish, population-based, longitudinal study.

BACKGROUND: The use of biologics in paediatric-onset inflammatory bowel disease (PIBD) is rapidly changing. AIMS: To identify the incidence and prevalence of biologic use within Scottish PIBD services, and to describe patient demographics and outcomes for those patients who required escalation of therapy beyond anti-tumour necrosis factor alpha (anti-TNFα) agents METHODS: We captured a nationwide cohort of prospectively identified patients less than 18 years of age with PIBD (A1 phenotype; diagnosed <17 years of age) within paediatric services over a 4.5-year period (1 January 2015-30 June 2019). All patients who received infliximab, adalimumab, vedolizumab or ustekinumab during the study period and/or received their first dose of these biologics were audited retrospectively. RESULTS: Scotland-wide PIBD-prevalence cases increased from 554 to 644 over the study period. A total of 495 incident new-start biological therapies were commenced on 403 PIBD patients: 295 infliximab (60%), 161 adalimumab (32%), 24 vedolizumab (5%) and 15 ustekunumab (3%). The proportion of new-start biologics changed with infliximab initiation rates decreasing (87%-54%) while adalimumab (13%-31%), vedolizumab (0%-9%) and ustekinumab (0%-6%) all increased. The incidence rate (first dose of new biologic not including biosimilar switch) increased from 6.9% to 8.1% over the study period and point prevalence rates (any biologic use) increased from 20.2% to 43.5% - an average annual percentage increase of 20%. Biosimilar penetration of new-start anti-TNFα agents increased from 3% to 91%. Demographics and outcomes of those patients receiving vedolizumab and ustekinumab were similar. CONCLUSIONS: Complete accrual of Scottish nationwide biologic usage within paediatric services demonstrates a rapidly changing, inexorably increasing PIBD biologics landscape.

Optimized Infliximab Induction Predicts Better Long-Term Clinical and Biomarker Outcomes Compared to Standard Induction Dosing.

OBJECTIVES: To evaluate the efficacy of standard and optimized infliximab induction dosing in attaining corticosteroid (CS) free clinical remission at week 52 and the effect that post-induction trough levels have on long-term outcome. METHODS: Inflammatory bowel disease (IBD) patients ≤18 years commenced on infliximab between August 1, 2016, and August 1, 2018, from Vancouver, Canada, and Glasgow, Scotland, were included. The Glasgow cohort followed standard induction while the Vancouver cohort undertook induction optimization based on clinical, biomarker, and proactive infliximab trough levels. Baseline characteristics and laboratory values were documented. RESULTS: In total, 140 children were included [median age 14.1 years (interquartile range (IQR) 12.0-16.0)]; 54% male. CS-free clinical remission at week 52 was higher in the optimized group compared to the standard cohort [65/78 (83%) vs. 32/62 (52%), P < 0.001]. Combined CS-free clinical and biomarker remission (CRP < 5 mg/L) was also higher in the optimized compared to the standard cohort [65/78 (83%) vs 25/62 (40%), P < 0.001]. The median post-induction trough level was higher in children who were in CS-free clinical remission at week 52 [3.6 mg/L (1.5-7.1)] vs. those who were not [2.0 mg/L (0.8-4.1), P = 0.04]. The odds of attaining a therapeutic post-induction trough level were almost 4-fold higher in the optimized group than the standard cohort (OR 3.97, 95% CI: 1.89-8.68, P < 0.001). CONCLUSIONS: Standard infliximab induction resulted in less favorable long-term outcomes for pediatric IBD patients. Optimizing induction using clinical, biomarker, and proactive trough levels resulted in higher post-induction trough levels and a greater odds of attaining long-term clinical remission.

Implications for sequencing of biologic therapy and choice of second anti-TNF in patients with inflammatory bowel disease: results from the IMmunogenicity to Second Anti-TNF therapy (IMSAT) therapeutic drug monitoring study.

BACKGROUND: Anti-drug antibodies are associated with treatment failure to anti-TNF agents in patients with inflammatory bowel disease (IBD). AIM: To assess whether immunogenicity to a patient's first anti-TNF agent would be associated with immunogenicity to the second, irrespective of drug sequence METHODS: We conducted a UK-wide, multicentre, retrospective cohort study to report rates of immunogenicity and treatment failure of second anti-TNF therapies in 1058 patients with IBD who underwent therapeutic drug monitoring for both infliximab and adalimumab. The primary outcome was immunogenicity to the second anti-TNF agent, defined at any timepoint as an anti-TNF antibody concentration ≥9 AU/ml for infliximab and ≥6 AU/ml for adalimumab. RESULTS: In patients treated with infliximab and then adalimumab, those who developed antibodies to infliximab were more likely to develop antibodies to adalimumab, than patients who did not develop antibodies to infliximab (OR 1.99, 95%CI 1.27-3.20, p = 0.002). Similarly, in patients treated with adalimumab and then infliximab, immunogenicity to adalimumab was associated with subsequent immunogenicity to infliximab (OR 2.63, 95%CI 1.46-4.80, p < 0.001). For each 10-fold increase in anti-infliximab and anti-adalimumab antibody concentration, the odds of subsequently developing antibodies to adalimumab and infliximab increased by 1.73 (95% CI 1.38-2.17, p < 0.001) and 1.99 (95%CI 1.34-2.99, p < 0.001), respectively. Patients who developed immunogenicity with undetectable drug levels to infliximab were more likely to develop immunogenicity with undetectable drug levels to adalimumab (OR 2.37, 95% CI 1.39-4.19, p < 0.001). Commencing an immunomodulator at the time of switching to the second anti-TNF was associated with improved drug persistence in patients with immunogenic, but not pharmacodynamic failure. CONCLUSION: Irrespective of drug sequence, immunogenicity to the first anti-TNF agent was associated with immunogenicity to the second, which was mitigated by the introduction of an immunomodulator in patients with immunogenic, but not pharmacodynamic treatment failure.

Thromboprophylaxis Use in Paediatric Inflammatory Bowel Disease: An International RAND Appropriateness Panel.

BACKGROUND AND AIMS: Thromboprophylaxis use in paediatric inflammatory bowel disease [IBD] is inconsistent. Current guidelines only support treating children with acute severe colitis with risk factors. We convened an international RAND panel to explore thromboprophylaxis in paediatric IBD inpatients in the context of new evidence. METHODS: We convened a geographically diverse 14-person panel of paediatric gastroenterologists alongside supporting experts. An online survey was sent before an online meeting. Panellists were asked to rate the appropriateness of thromboprophylaxis in hospitalised paediatric IBD patients via 27 scenarios of varying ages, gender, and phenotype, with and without thrombotic risk factors. Anonymised results were presented at the meeting. A second modified survey was distributed to all panellists present at the meeting. Results from the second survey constitute the RAND panel results. The validated RAND disagreement index defined disagreement when ≥ 1. RESULTS: The combined outcome of thromboprophylaxis being considered appropriate until discharge and inappropriate to withhold was seen in 20 of 27 scenarios, including: all patients with new-onset acute severe colitis; all flares of known ulcerative colitis, irrespective of risk factors except in pre-pubescent patients with limited disease and no risk factors; and all Crohn's patients with risk factors. Disagreement was seen in five scenarios regarding Crohn's without risk factors, where outcomes were already uncertain. CONCLUSIONS: RAND panels are an established method to assess expert opinion in areas of limited evidence. This work therefore constitutes neither a guideline nor a consensus; however, the findings suggest a need to re-evaluate the role of thromboprophylaxis in future guidelines.

Intestinal fatty acid binding protein is a disease biomarker in paediatric coeliac disease and Crohn's disease.

BACKGROUND: There is a clinical need to develop biomarkers of small bowel damage in coeliac disease and Crohn's disease. This study evaluated intestinal fatty acid binding protein (iFABP), a potential biomarker of small bowel damage, in children with coeliac disease and Crohn's disease. METHODS: The concentration iFABP was measured in plasma and urine of children with ulcerative colitis, coeliac disease, and Crohn's disease at diagnosis and from the latter two groups after treatment with gluten free diet (GFD) or exclusive enteral nutrition (EEN), respectively. Healthy children (Controls) were also recruited. RESULTS: 138 children were recruited. Plasma but not urinary iFABP was higher in patients with newly diagnosed coeliac disease than Controls (median [Q1, Q3] coeliac disease: 2104 pg/mL 1493, 2457] vs Controls: 938 pg/mL [616, 1140], p = 0.001). Plasma or urinary iFABP did not differ between patients with coeliac on GFD and Controls. Baseline iFABP in plasma decreased by 6 months on GFD (6mo GFD: 1238 pg/mL [952, 1618], p = 0.045). By 12 months this effect was lost, at which point 25% of patients with coeliac disease had detectable gluten in faeces, whilst tissue transglutaminase IgA antibodies (TGA) continued to decrease. At diagnosis, patients with Crohn's disease had higher plasma iFABP levels than Controls (EEN Start: 1339 pg/mL [895, 1969] vs Controls: 938 pg/mL [616, 1140], p = 0.008). iFABP did not differ according to Crohn's disease phenotype. Induction treatment with EEN tended to decrease (p = 0.072) iFABP in plasma which was no longer different to Controls (EEN End: 1114 pg/mL [689, 1400] vs Controls: 938 pg/mL [616, 1140], p = 0.164). Plasma or urinary iFABP did not differ in patients with ulcerative colitis from Controls (plasma iFABP, ulcerative colitis: 1309 pg/mL [1005, 1458] vs Controls: 938 pg/mL [616, 1140], p = 0.301; urinary iFABP ulcerative colitis: 38 pg/mg [29, 81] vs Controls: 53 pg/mg [27, 109], p = 0.605). CONCLUSIONS: Plasma, but not urinary iFABP is a candidate biomarker with better fidelity in monitoring compliance during GFD than TGA. The role of plasma iFABP in Crohn's disease is promising but warrants further investigation. TRIAL REGISTRATION: Clinical Trials.gov, NCT02341248. Registered on 19/01/2015.

The Impact of Compliance During Exclusive Enteral Nutrition on Faecal Calprotectin in Children With Crohn Disease.

ABSTRACT: It remains unclear whether suboptimal response to exclusive enteral nutrition (EEN) in some children with Crohn disease (CD) is explained by poor compliance. The present study measured faecal gluten immunogenic peptides (GIP), a biomarker of gluten intake, in 45 children (3- 17 years) with CD, and explored associations with faecal calprotectin (FC) levels at 33 and 54 days of EEN. FC decreased in patients with undetectable GIP at both 33 and 54 days of EEN (mean decrease, 33 days: -743 mg/kg, 54 days: -1043 mg/kg, P  < 0.001) but not in patients who had detectable levels. At EEN completion, patients with undetectable GIP had a lower FC by 717 mg/kg compared with patients with a positive GIP result (P = 0.042) and demonstrated a greater decline from baseline FC (-69% vs +5%, P = 0.011). Poorer response to EEN is explained in part by diminished compliance. Faecal GIP might be useful as proxy biomarker of EEN compliance.

Primary Care Physicians', Psychiatrists', and Oncologists' Coordination While Prescribing Medications for Patients With Multiple Chronic Conditions.

OBJECTIVES: Coordination of medication prescribing is important in the care of patients with multiple chronic conditions (MCC) given the involvement of multiple providers and multiple medications used to manage MCC. The objective of this study was to identify physician and practice factors associated with physicians' coordination of prescribing for complex patients with MCC. METHODS: Our cross-sectional study used a 33-item anonymous, online survey to assess physicians' coordination practices while prescribing for patients with MCC. We sampled primary care physicians (PCPs), psychiatrists, and oncologists across the United States. Coordination of medication prescribing was measured on a 7-point Likert-type scale. χ2, Fisher exact test, and binomial logistic regression, adjusted for factors and covariates, were used to determine differences in coordination of prescribing. Average marginal effects were calculated for factors. RESULTS: A total of 50 PCPs, 50 psychiatrists, and 50 oncologists participated. Most psychiatrists (56%) and oncologists (52%) reported frequently coordinating prescribing with other physicians, whereas less than half of the PCPs (42%) reported frequently coordinating prescribing. Female physicians were 25% points more likely to report coordinating prescribing than male physicians (P = 0.0186), and physicians not using electronic medical records were 30% points more likely to report coordinating prescribing than physicians using electronic medical records (P = 0.0230). Four additional factors were associated with lower likelihood of coordinating prescribing. CONCLUSIONS: Physician and practice factors may influence differences in coordination of medication prescribing, despite physician specialty. These factors can provide a foundation for developing interventions to improve coordination of prescribing practices for MCC.

The association of continuity of care and risk of mortality in breast cancer patients with cardiometabolic comorbidities.

OBJECTIVE: The association of continuity of care (COC) among providers and mortality risk for breast cancer patients with comorbidities is not sufficiently studied. DESIGN: A retrospective cohort study using the 2006-2014 Surveillance, Epidemiology and End Results (SEER)-Medicare data. PARTICIPANTS: Newly diagnosed female breast cancer patients (n = 57,578) with comorbidities (hypertension, hyperlipidemia, and/or diabetes). METHODS: All-cause mortality was assessed annually for up to 5 years. COC was estimated using the Bice-Boxerman index, which included: 1) specialty COC capturing continuity of visits to the same provider type (Primary Care Physicians, Oncologists, and Other specialists) and 2) individual COC capturing continuous care to the same provider regardless of provider specialty. Cox proportional hazards models estimated the hazard ratio (HR) of all-cause mortality across quartile of the COC index. RESULTS: Mortality was positively associated with advanced tumor stages and number of comorbidities (p < 0.05). Patients with high specialty COC (4th vs. 1st quartile, HR 1.34, 95%CI 1.29-1.40) had higher risks of mortality compared with those with low specialty COC. However, patients with high individual COC (4th vs. 1st quartile, HR 0.53, 95%CI 0.51-0.54) had lower risks of mortality compared to those with low individual COC. CONCLUSION: Receiving care from fewer providers is associated with lower mortality and from fewer types of provider is associated with higher mortality. The results might be confounded by uncontrolled factors and provoke the need for alternative patient care models that recognize the balance between appropriate subspecialties and minimizing the fragmentation of care within and across subspecialties.

Pomalidomide plus dexamethasone for patients with relapsed or refractory multiple myeloma: Final results of the non-interventional study POSEIDON and comparison with the pivotal phase 3 clinical trials.

BACKGROUND: Prognosis of patients with multiple myeloma (MM) who have relapsed on or become refractory to immunomodulators and bortezomib is poor, and treatment options are limited. While pomalidomide plus low-dose dexamethasone (POM/DEX) has demonstrated efficacy in clinical trials, real-world evidence is scarce. PATIENTS AND METHODS: POSEIDON was a prospective non-interventional study designed to evaluate effectiveness, safety and quality of life (QoL) of POM/DEX in patients with relapsed or refractory MM (R/RMM) pretreated with at least two prior therapy lines including both lenalidomide and bortezomib in real world in Germany. Patients received POM/DEX according to physicians' choice. Data were analyzed descriptively. RESULTS: Between 2014 and 2017, 151 patients were enrolled, 144 patients with a median of three prior therapy lines qualified for effectiveness analysis. Median age was 73.2 years. Median progression-free and overall survival were 6.3 months [95% confidence interval (CI) 5.2, 8.6] and 12.9 months [95% CI 10.6, 15.1]. Most frequent grade 3/4 adverse events were leukopenia (8.2%), pneumonia (7.5%) and anemia (5.5%). QoL was maintained after start of POM/DEX. CONCLUSION: The results of POSEIDON support the effectiveness and safety of POM/DEX in R/RMM patients pretreated with lenalidomide and bortezomib and highlight the clinical value of the POM/DEX regimen in the real-world setting. Registered at clinicaltrials.gov (NCT02075996).

Helicobacter pylori: getting to grips with the guidance.

Helicobacter pylori is a Gram-negative bacterium that inhabits the mucus layer above the gastric mucosa. While infection rates vary by region, the global prevalence is estimated at 50%. While asymptomatic carriage is common, infection can result in significant morbidity and mortality from complications including peptic ulcer disease, atrophic gastritis and gastric cancer. Paediatric and adult practices diverge due to differences in complication rate, symptomatology, practicalities with investigations and treatment options. Widespread use of standard antibiotic regimens has however resulted in a rapid global increase in antibiotic resistance and treatment failure in all ages. There is urgent need to optimise treatment regimens and maximise first-time eradication rates. This need is reflected in the latest guidelines from the European Society for Paediatric Gastroenterology Hepatology and Nutrition and the North American Society for Pediatric Gastroenterology, Hepatology and Nutrition for paediatric practice and the Maastricht Guidelines for adult practice. This article aims to provide a practical overview of the investigations and management of H. pylori by comparing and contrasting these guidelines.

Geographic distribution of Pythium insidiosum infections in the United States.

OBJECTIVE: To describe the geographic distribution of infections caused by Pythium insidiosum in dogs, horses, and other animal species in the US. ANIMALS: For the last 20 years, we have collected data from cases of pythiosis in 1,150 horses, 467 dogs, and other species (59) from various geographic locations in the US. PROCEDURES: Due to lost data (from 2006 to 2016), the selected cases include years 2000 to 2005 and 2016 to 2020. The selection of cases was based on infected host clinical features, serum samples demonstrating strong positive anti-P insidiosum IgG titers in serologic assays, and positive results on ≥ 1 of the following diagnostic modalities: microbial culture on 2% Sabouraud dextrose agar, histologic evaluation, PCR assay, and wet mount cytologic evaluation (with potassium hydroxide). RESULTS: Most confirmed P insidiosum infections were found in horses and dogs in the southeastern US. Interestingly, in Texas, no cases were found west of longitude 100°W. Few pythiosis cases were diagnosed in west-coast states. Equine cases were more often diagnosed during summer and fall months, but canine cases were more often diagnosed between September and February. Cases in other species were discovered in the same geographic areas as those in dogs and horses. CLINICAL RELEVANCE: To our knowledge, this is the first report providing the ecological distribution of P insidiosum infection in affected species in the US. Results of this study illustrated the importance of including P insidiosum in the differential diagnostic scheme of nonhealing skin lesions or intestinal granulomatous masses, particularly in dogs and horses inhabiting or having visited endemic areas.

Dietary triggers of gut inflammation following exclusive enteral nutrition in children with Crohn's disease: a pilot study.

BACKGROUND: The anti-inflammatory effect of exclusive enteral nutrition on the gut of children with Crohn's disease is rapidly lost after food reintroduction. This study assessed disease dietary triggers following successful treatment with exclusive enteral nutrition. METHODS: Nutrient intake, dietary patterns and dietary biomarkers in faeces (gluten immunogenic peptides, undigestible starch, short chain fatty acids) were assessed in 14 children with Crohn's disease during early food reintroduction, following exclusive enteral nutrition. Groups above (Group A) and below (Group B) the median levels of faecal calprotectin after food reintroduction were assigned for comparative analysis. RESULTS: Intakes of fibre, gluten-containing cereals and red and processed meat were significantly higher in Group A than Group B; (median [Q1, Q3], g/day; Fibre: 12.1 [11.2, 19.9] vs. 9.9 [7.6, 12.1], p = 0.03; Red and processed meat: 151 [66.7, 190] vs. 63.3 [21.7, 67], p = 0.02; gluten-containing cereals: 289 [207, 402] vs. 203 [61, 232], p = 0.035). A diet consisting of cereals and meat products was predictive (92% accuracy) of higher faecal calprotectin levels after food reintroduction. In faeces, butyrate levels, expressed as absolute concentration and relative abundance, were higher in Group A than Group B by 28.4 µmol/g (p = 0.015) and 6.4% (p = 0.008), respectively. Levels of gluten immunogenic peptide and starch in faeces did not differ between the two groups. CONCLUSIONS: This pilot study identified potential dietary triggers of gut inflammation in children with Crohn's disease after food reintroduction following treatment with exclusive enteral nutrition. TRIAL REGISTRATION: Clinical trials.gov registration number: NCT02341248; Clinical trials.gov URL: https://clinicaltrials.gov/ct2/show/NCT02341248 (retrospectively registered).

Kidney Dysfunction Is Associated with Thrombosis and Disease Severity in Myeloproliferative Neoplasms: Implications from the German Study Group for MPN Bioregistry.

Inflammation-induced thrombosis represents a severe complication in patients with myeloproliferative neoplasms (MPN) and in those with kidney dysfunction. Overlapping disease-specific attributes suggest common mechanisms involved in MPN pathogenesis, kidney dysfunction, and thrombosis. Data from 1420 patients with essential thrombocythemia (ET, 33.7%), polycythemia vera (PV, 38.5%), and myelofibrosis (MF, 27.9%) were extracted from the bioregistry of the German Study Group for MPN. The total cohort was subdivided according to the calculated estimated glomerular filtration rate (eGFR, (mL/min/1.73 m2)) into eGFR1 (≥90, 21%), eGFR2 (60-89, 56%), and eGFR3 (<60, 22%). A total of 29% of the patients had a history of thrombosis. A higher rate of thrombosis and longer MPN duration was observed in eGFR3 than in eGFR2 and eGFR1. Kidney dysfunction occurred earlier in ET than in PV or MF. Multiple logistic regression analysis identified arterial hypertension, MPN treatment, increased uric acid, and lactate dehydrogenase levels as risk factors for kidney dysfunction in MPN patients. Risk factors for thrombosis included arterial hypertension, non-excessive platelet counts, and antithrombotic therapy. The risk factors for kidney dysfunction and thrombosis varied between MPN subtypes. Physicians should be aware of the increased risk for kidney disease in MPN patients, which warrants closer monitoring and, possibly, early thromboprophylaxis.

Epstein-Barr Virus Status and Subsequent Thiopurine Exposure Within a Paediatric Inflammatory Bowel Disease Population.

ABSTRACT: The use of thiopurine therapy in Epstein-Barr virus (EBV)-naïve inflammatory bowel disease (IBD) patients remains controversial due to a risk of EBV-associated complications. We evaluated EBV status and outcomes within our paediatric IBD population over an 8-year period; finding that 217 of 409 (53%) screened patients were seropositive for EBV at IBD diagnosis; that thiopurines were used in 189 of 217 (87%) seropositive and 159 of 192 (83%) seronegative patients (P = 0.22); and that 7 of 192 (4%) previously seronegative patients subsequently tested positive for EBV with 6 of 7 (86%) patients having concurrently recorded thiopurine use. All six patients continued thiopurine with/without a period of cessation; no EBV-associated lymphoproliferative disorders/serious complications were recorded within our cohort. A significant proportion of our patients would not receive thiopurine therapy should their use be avoided in EBV-negative patients (47%) or seronegative males (30%). The small but significant risks of thiopurine treatment must be balanced against the potential benefits of successful IBD management; further research into this is required.

The impact of cognitive impairment on survival and medication adherence among older women with breast cancer.

INTRODUCTION: The purpose of this study was to examine the impact of preexisting cognitive impairments on survival and medication adherence, and whether chronic medication adherence mediates or moderates the association between cognitive impairments and mortality in patients with breast cancer. METHODS: This retrospective cohort study of older female patients diagnosed with breast cancer was conducted using the Surveillance, Epidemiology, and End Results Medicare Linked Database. We examined the risk of mortality from cancer and non-cancer causes in patients with and without a history of cognitive impairment. In addition, we examined if chronic medication adherence rates differ between these groups of patients and if medication adherence mediates or moderates the association between cognitive impairments and non-cancer mortality. RESULTS: Mortality from cancer-specific (HR 1.13, 95% CI 1.04-1.23) and non-cancer causes (HR 1.16, 95% CI 1.11-1.21) as well as all-cause mortality (HR 1.30, 95% CI 1.23-1.38) was significantly higher in patients with cognitive impairments compared to those without cognitive impairment. Both groups showed low adherence levels to chronic medication before and after the breast cancer diagnosis. Further analysis did not show that medication adherence mediates or moderates the relationship between cognitive impairment and non-cancer mortality (p value > 0.05). CONCLUSION: The results of this study indicate that older female patients with cognitive impairments and a breast cancer diagnosis have a heightened risk of cancer-specific and non-cancer mortality. Our findings do not indicate that chronic medication adherence plays a role in the association between a history of cognitive impairment and mortality, it is still necessary to further investigate this issue.