Methods: A prospective, controlled, cohort study. Children (1-15 years) with recent AGE (cases) and siblings (controls) were followed for 6 months. We assessed DGBIs using a validated questionnaire (QPGS IV) per Rome criteria. Patients with underlying GI disorders (eg. Celiac, IBD, recent abdominal surgery) were excluded.
Key findings:
Among children without a history of DGBI before the AGE, 6 (12.2%) cases vs 0 control were diagnosed with DGBI (P = 0.01) at follow-up at 3 months
At 6 months, 5 cases (1 lost to follow-up) vs 0 control had persistent DGBI (P = 0.03)
Severity of AGE was correlated with PI-DGBI. Severe AGE included abdominal pain, ED consullt, and need for IV fluids
My take: It is well-known that previous AGE increases the risk of PI-DGBIs, especially irritable bowel syndrome. However, this is the first prospective cohort study showing this association between AGE and DGBIs in a nonoutbreak setting. In addition, it correlates the risk of DGBI with the severity of AGE.
Background: MORF-057 is an orally administered small-molecule drug that inhibits α4β7 integrin-mediated recruitment of α4β7-expressing lymphocytes to the gut. It has a similar target as vedolizumab, a monoclonal anti-integrin antibody used to treat ulcerative colitis (approved in 2014), but it requires parenteral administration.
Methods: This open-label, phase 2a, single-arm, multicenter trial (EMERALD-1) comprised a 6-week screening period, a 52-week active treatment period (including a 12-week induction period and 40-week maintenance period), and a 4-week safety follow-up period. Of the 35 participants enrolled in the main cohort, 18 participants received 100 mg of oral MORF-057 twice daily for the entire treatment period.
The primary efficacy endpoint was a change in the Robarts Histopathology Index (RHI) score from baseline to week 12. “RHI was chosen as the primary efficacy assessment because it is an objective measure that can be assessed in a blinded fashion, which was critical given the open label study design. RHI also allows for a deeper, more quantitative probe than endoscopy.”
Key findings:
MORF-057 was well tolerated, and no treatment-emergent serious adverse events were observed
At week 12, participants (n= 35) exhibited a mean change from baseline in RHI score of ‒6.4 (standard deviation, 11.2). Additionally, 22.9% of participants (8/35) achieved RHI remission (RHI score ≤3)
In participants with evaluable data (n=18), the effects of MORF-057 on pharmacokinetics, pharmacodynamics, and clinical efficacy were achieved at week 12 and remained consistent to week 52
Symptomatic remission based on whether patient was advanced therapy (AT)-naive or AT-experienced
My take: This small open label study shows that an oral medication targeting α4β7 integrin has potential as an effective therapy for ulcerative colitis. If effective, then it would be important to understand how it compares to vedolizumab.
M Matar et al. J Pediatr Gastroenterol Nutr. 2026;82:487–494. Chronic nonbacterial osteomyelitis associated with pediatric inflammatory bowel disease: : A multicenter retrospective study from the Paediatric inflammatory bowel disease Porto Group of ESPGHAN
Methods: Retrospective study with 45 pediatric patients with inflammatory bowel disease (n=32 with Crohn’s disease, n=8 with ulcerative colitis, n=5 with IBD-U)
Key findings:
CNO presented in 15 patients (33%) within 3 months of IBD diagnosis, and in additional 20 (44%) patients after IBD diagnosis; in 10 (22%) patients CNO preceded the diagnosis of IBD with a median time 46 (25–248) weeks
11 (24%) subjects displayed at least one additional extra-intestinal manifestations, including arthritis (6, 13%), erythema nodosum (4, 9%), sacro-ileitis (2, 4%), psoriasis (1, 2%), and pyoderma gangrenosum (1, 2%).
Complications occurred in six patients and included vertebral collapse, bone fracture, and bone deformity. In eight (18%) subjects vertebral collapse was present already at the time of diagnosis.
“While in most patients, diagnosis of CNO was associated with either clinical or laboratory indices of active IBD, especially CD, in some cases, the intestinal disease was quiescent.”
“All patients achieved remission of CNO at some point during follow-up, which may support the hypothesis that anti-TNF treatment is unlikely to promote CNO development and does not reinforce the theory of a paradoxical effect that has been suggested by Cordesse et al.22“
My take: This is a useful review highlighting the association of CNO with both active disease and quiescent IBD. The authors argue that their data does not support the development of CNO as a paradoxical effect. I disagree with this premise. Many of the extraintestinal manifestations, that anti-TNF agents can treat, rarely can be caused by them. Besides CNO, paradoxical reactions to anti-TNF agents have included the development of rheumatoid arthritis, psoriasis, hidradenitis suppurativa and autoimmune liver disease.
Background: “The availability of antibiotic susceptibility data is essential for understanding local and regional resistance patterns and for informing future guidelines on optimal treatment regimens for children.” This quality improvement project report documents how “using a standardized checklist, in combination with educational initiatives for staff physicians and collaborative efforts with endoscopy and laboratory teams, were effective strategies to increase the use of gastric biopsy culture as a diagnostic tool for H. pylori infection and, to a lesser extent, to improve culture yield in patients with positive histology.”
Key steps:
Standardized checklist for biopsy collection used by nurses
Standardized transport protocol
Prompt refridgeration/transportation
Using a single lab for testing (Mayo clinic)
Key findings:
There was a consistent increase in culture positivity for H pylori and this was associated with improved eradication rates
Overall, antimicrobial resistance was highest for metronidazole (27.5%) and clarithromycin (18.7%), and lower for rifampin (12.2%), levofloxacin (10.1%), and amoxicillin (4.3%). Only one isolate showed resistance to tetracycline
Discussion: “Among the various interventions implemented during the QI project, the one that appears to have contributed most significantly to the dramatic improvement in culture yield among patients with H. pylori-positive histology was the consolidation of specimen processing to a single specialty laboratory [Mayo clinic].” Specific logistics included using a simple sterile container with saline-moistened tissue for collection and sending samples to specialty lab on the same day as collection.
My take: During this project, there was improved use of gastric culture and in culture yield. This resulted in meaningful improvement for patients. However, without clinical leadership to implement these changes, there will continue to be suboptimal eradication rates at other centers.
G Bora et al. JPGN Reports. 2026;7:1–5. Open Access! Maralixibat for the treatment of severe xanthomas in two children with Alagille syndrome: Case reports
Key findings:
Maralixibat (MRX) resulted almost complete resolution of severe, debilitating xanthomas and clinically meaningful improvements in pruritus/serum bile acid levels.
Clinical scratch score in Case 1 dropped from baseline of 4 to 2 after MRX; in Case 2, it dropped from 3 to 1 after MRX
Serum bile acids in Case 1 dropped from baseline of 468 micromol/L to 206 after MRX; in Case 2 it dropped from 57 to 25 after MRX
This case report involved two patients with ALGS and unusual manifestations of xanthomatosis, including one patient with airway xanthomas and a second patient with severe, diffuse xanthomas
From Figure 1 showing airway and skin changes in case 1:
Rigid bronchoscopy before (C) and then 18 months after maralixibat (E)
Discussion:
“The ICONIC study by Gonzales et al. showed significant improvements in xanthomas in participants treated with maralixibat by 48 weeks, based on overall reductions in the Clinician Xanthomas Score, with further improvements in patients treated for longer durations. Xanthoma reduction was associated with improved quality of life and levels of TC.4 This report reviewed real-world experience in two patients with ALGS and characterized the extent of their improvement after treatment with maralixibat.”
My take: This report provides convincing evidence that maralixibat was associated with reversing severe xanthomas in these two patients with Alagille syndrome.
Disclaimer: This blog, gutsandgrowth, assumes no responsibility for any use or operation of any method, product, instruction, concept or idea contained in the material herein or for any injury or damage to persons or property (whether products liability, negligence or otherwise) resulting from such use or operation. These blog posts are for educational purposes only. Specific dosing of medications (along with potential adverse effects) should be confirmed by prescribing physician. Because of rapid advances in the medical sciences, the gutsandgrowth blog cautions that independent verification should be made of diagnosis and drug dosages. The reader is solely responsible for the conduct of any suggested test or procedure. This content is not a substitute for medical advice, diagnosis or treatment provided by a qualified healthcare provider. Always seek the advice of your physician or other qualified health provider with any questions you may have regarding a condition.
This retrospective single-center study with 34 pediatric patients with inflammatory bowel disease examined the laboratory costs (2020-2021) associated with monitoring biologic therapy.
Methods: “Routine laboratory studies were defined as those part of the standardized infusion protocol at SBCH and were obtained with each scheduled infusion. The following laboratory studies were considered routine/standard: complete blood count with differential, basic metabolic panel, liver function tests, amylase, lipase, erythrocyte sedimentation rate, C-reactive protein, vitamin D, iron, ferritin, vitamin B12, folate, urine hCG (if a subject was female). Other laboratory studies that were collected, but not considered routine studies included QuantiFERON-TB, and biologic drug and antibody level.”
Key findings:
The average hospital charge for studies obtained per infusion was $1308.36 with an average annual cost of $9543.44 per patient
Fifteen (6%) instances of change in clinical management were found. “Only a limited subset of the 15 laboratory studies included were utilized in making changes: biologic drug, Vitamin D, and iron level”
During the study, 248 infusions were administered with a “total annual charge amongst all patients in the study was $324,447”
Discussion:
“Our study population had well controlled disease as evident by low PCDAI and PUCAI scores…Our observations suggest the utility of routine laboratory surveillance at each biologic infusion is minimal, favoring decreased testing for IBD patients, especially those in clinical remission.”
“We propose obtaining laboratory tests twice a year, or with every third infusion, for patients with mild disease or in remission based on their disease activity index scores. In our small cohort of patients, this change in practice would reduce the total annual costs by 66% ($214,154.82)”
My take: It has been my practice, for most patients with IBD, to obtain labs with every other infusion (~3 times per year). Typically, I will obtain a CBC/d, CMP and CRP and obtain other labs like Vit D, GGT, Quantiferon Gold and drug level monitoring less frequently. I rarely check Vit B12, ESR, Folate, Amylase, and Lipase.
Disclaimer: This blog, gutsandgrowth, assumes no responsibility for any use or operation of any method, product, instruction, concept or idea contained in the material herein or for any injury or damage to persons or property (whether products liability, negligence or otherwise) resulting from such use or operation. These blog posts are for educational purposes only. Specific dosing of medications (along with potential adverse effects) should be confirmed by prescribing physician. Because of rapid advances in the medical sciences, the gutsandgrowth blog cautions that independent verification should be made of diagnosis and drug dosages. The reader is solely responsible for the conduct of any suggested test or procedure. This content is not a substitute for medical advice, diagnosis or treatment provided by a qualified healthcare provider. Always seek the advice of your physician or other qualified health provider with any questions you may have regarding a condition.
Methods: “The multicentre, double-blind, treat-through, multi-dose, randomised, placebo-controlled, phase 2b, TUSCANY-2 trial” enrolled 228 people who completed induction. All patients had moderate to severe ulcerative colitis who were treated with either subcutaneous afimkibart (a TNF-like ligand 1A (TL1A)) or placebo. There was a 12-week induction phase followed by a 40-week maintenance phase.
Key findings:
At week 14, the primary endpoint of clinical remission by total Mayo score was reported in 12 (26%) of 47 patients in the afimkibart 50 mg group, 14 (23%) of 60 patients in the afimkibart 150 mg group, and 21 (24%) of 88 patients in the in the afimkibart 450 mg group versus five (12%) of 43 patients in the placebo group
Incidences of treatment-emergent adverse events during induction were similar with placebo and afimkibart
The percentages of remission were higher for every afimkibart dose but this did not reach statistical significance compared to placebo
My take: Further testing is needed to determine whether afimkibart will have a significant place for treatment of inflammatory bowel disease.
Background: “Since vedolizumab is a gut-selective anti-α4β7 integrin, its effect on EIMs has been a matter of debate, with relevant data lacking in pediatric IBD. A systematic review, which included three interventional studies, five non-interventional studies, and three case series, concluded that there is insufficient evidence supporting the efficacy of vedolizumab for treating pre-existing EIMs in adults.3“
Methods: This was a subgroup analysis of the pediatric VedoKids cohort, a multicenter, prospective “real-life” study of children (aged 0–18 years) with IBD treated with vedolizumab and followed through 54 weeks.
Key findings:
EIMs were identified in 18/142 (12.6%) children at baseline
Children with EIMs had an average age of diagnosis of 9 yrs compared to 12 yrs in those without EIMs
Children with EIMs had higher rate of pancolitis in UC and ileocolonic distribution in CD
Prior anti-TNF medication was noted in 16 (89%) of EIM cohort compared to 74 (60%) of non-EIM cohort
Concomitant medications were administered in 72% of EIM cases and to a similar number of non-EIM patients. For EIM patients, ASA were given in 7, steroids in 10, thiopurines in 4 and methotrexate in 2
Children with EIMs had more active disease (see below)
EIM resolution rate of 89%, mainly occurring within the early weeks of vedolizumab treatment
My take: While this study has several limitations, including the high rate of concomitant medications, it shows that most patients receiving vedolizumab had resolution of their EIMs. In addition, it shows that patients with EIMs had a more severe IBD phenotype.
Background: Mirikizumab, a immunoglobulin G4 monoclonal antibody, targets the p19 subunit of IL-23, with demonstrated efficacy and safety in adults with ulcerative colitis and Crohn’s disease.
Methods: This 52-week, multicenter, open-label, non-randomized, phase 2 study enrolled pediatric participants (n=26, 2 to <18 years) with moderately-to-severely active ulcerative colitis with inadequate or loss of response or intolerance to corticosteroids, immunomodulators, biologics, or JAK inhibitors.
Key findings:
At week 12: 18 (69·2%) participants had a clinical response by modified Mayo score (mMS), ten (38·5%) achieved clinical remission by mMS, 14 (53·8%) achieved endoscopic remission
At week 12: 20 (76·9%) of the 26 participants had a clinical response based on Pediatric Ulcerative Colitis Activity Index (PUCAI), and ten (38·5%) achieved clinical remission at week 12
At week 52: 14 (53·8%) of 26 participants achieved mMS-based clinical response, ten (38·5%) were in mMS-based clinical remission, ten (38·5%, 95% CI 22·4–57·5) of 26 patients were in endoscopic remission
At week 52: 14 (53·8%) had a PUCAI-based clinical response and 13 (50·0%) were in PUCAI-based clinical remission
Three (12%) participants experienced serious adverse events across induction and maintenance periods (non-infective appendicitis, worsening of ulcerative colitis, and pseudarthrosis), of which one (worsening of ulcerative colitis) led to study discontinuation
My take: In this pediatric population with high prior advanced therapy exposure, there was a good response to mirikizumab. This trial which was limited by a lack of an active comparator group was started prior to the medication approval in adults. Overall, the IL-23 class of medications has emerged as an effective drug class for inflammatory bowel disease.
In a previous blog post in 2019, it was noted how the IRS proved that having health insurance saved lives (How The IRS Proved That Health Insurance Saves Lives); just receiving a letter recommending getting coverage reduce deaths by ~1 in 1600. Another study in 2014 (in Massachusetts) showed that for“every 830 additional people who got insurance under Massachusetts’ health reforms prevented roughly one death.” If this were extrapolated to broaden health care coverage to everyone in the U.S this could amount to preventing 20,000-45,000 deaths per year (A Leading Cause of Mortality in U.S…. and 45,000 Unnecessary Deaths Per Year).
A new study shows how important ACA expansion has been to improved liver outcomes:
This review identified twenty-seven studies that met inclusion criteria across 4 clinical categories: hepatitis C virus (n = 4), liver transplantation (n = 10), hepatocellular carcinoma (n = 9), and cirrhosis or CLD (n = 5).
Key findings:
Twenty-three out of 27 studies showed patients benefited from the ACA, which notably included improved liver-related mortality in Medicaid-expansion (ME) states.
“Difference-in-difference analyses showed liver transplantation listing increased by 1.8% to 6.0% in ME vs NME states; early-stage hepatocellular carcinoma (HCC) diagnosis increased by 5.4%, and cirrhosis-related mortality rose more slowly in ME states (0.5–1.0 per 100,000 vs 1.4–10.4 per 100,000).”
HCV studies showed improved access to direct-acting antiviral therapy in ME states. Expansion states consistently reported higher direct-acting antiviral prescription rates and Medicaid reimbursement levels compared with NME states.
HCC survival outcomes improved more consistently in ME than in NME states after ACA implementation (median overall survival, 7.3 months versus 4.5 months, respectively).
Of the five studies that examined chronic liver disease and cirrhosis, ME was associated with lower emergency department readmissions, shorter hospital stays, and reduced hospitalization costs.
My take: The study findings, while not surprising, quantifies some of the improvements in survival and outcomes for patients who gained access to health insurance.
45,000 Unnecessary Deaths Per Year (2013): “45,000 American adults die each year because they have no medical coverage (Am J Public Health 2009; 99: 2289-95)”
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