Expenditure and survival of adult patients with intestinal failure due to short bowel syndrome: real-world evidence from Southern Finland.

OBJECTIVES: Comprehensive follow-up data from the largest hospital district in Finland was used to assess hospital-based healthcare resource utilization (HCRU) and expenses, incidence and prevalence, survival, and effect of comorbidities/complications on survival of adult patients with intestinal failure due to short bowel syndrome (SBS-IF). METHODS: This study utilized electronic healthcare data covering all ≥18-year-old patients with SBS-IF at the Hospital District of Helsinki and Uusimaa in Finland between 2010 and 2019. Patients were followed from SBS-IF onset until the end of 2020 or death and compared to birth year and sex-matched control patients without SBS-IF. RESULTS: The study included 77 patients with SBS-IF (cases) and 363 controls. Cases had high HCRU; the cumulative expenses were about tenfold compared to the controls, at the end of the study (€123,000 vs. €14,000 per patient). The expenses were highest during the first year after SBS-IF onset (€53,000 per patient). Of the cases with a median age 62.5 years, 51.9% died during study time. The median survival was 4.4 years from SBS-IF onset and cases died 13.5 times more likely during the follow-up compared to controls. Mortality risk was lower in female cases (hazard ratio (HR) 0.46; 95% confidence intervals (CI) 0.24, 0.9) and higher with presence of comorbidities (Charlson comorbidity index HR 1.55; 95% CI 1.2, 2.0) and mesenteric infarction (HR 4.5; 95% CI 1.95, 10.36). The incidence of adult SBS-IF was 0.6 per 100,000 adults. CONCLUSION: Our study demonstrates a high demand for healthcare support and elevated mortality in adult SBS-IF-patients. Our results suggest that the presence of comorbidities is a key driver for mortality.

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

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

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

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

Bowel function in a prospective cohort of 1052 healthy term infants up to 4 months of age.

The purpose of this study is to describe the defecation pattern of healthy infants up to 17 weeks of age. We included 1052 healthy term infants from the prospective HELMi cohort (NCT03996304). Parents filled in recurring online questionnaires on feeding, gastrointestinal function, and crying weekly for the first 17 weeks of life. Defecation frequency was highest at the age of 3 weeks (a median of 4 times/day, interquartile range (IQR) 2.9-5). At each time point, the median defecation frequency of breastfed infants was higher than that of infants receiving formula (e.g., at week 17 a median of 2 times/day, IQR 0.9-3.6, and a median of 1.1, IQR 0.6-1.4, respectively). The dominant color of the stool was most often yellow or light brown. Nearly black stools were reported in the first week of life in 3.4%. Nearly half (47.4%) of the infants had green stool color dominating for at least 1 week, with comparable frequency among breastfed (47.7%) and formula-fed (45.2%) infants. Green stools were associated with a higher defecation frequency (linear mixed-effect model p < 0.0001). Occasional blood in stool was reported in 9.3% and recurrent blood in 5.2% of the infants with no difference in stool consistency. Hard stools were rare (≤ 1%).     Conclusion: This study enlightens the spectrum of defecation patterns in healthy term infants during the first 17 weeks of life. A better understanding of bowel function helps healthcare professionals distinguish normal from abnormal when addressing defecation, the color of stools, and the type of feeding. What is Known: • Breastfed infants have more frequent and more yellow-colored stools than formula-fed infants. • Stools with green color are often suggested by the parents or even by medical professionals to indicate disease or discomfort in early life. What is New: • Nearly half of the healthy term infants had green stool dominating for at least one week during the first 17 weeks and occasional blood was reported in almost 10% of the infants during this period. • Data on normal variation in bowel function and stool may serve primary health care professionals when educating the families and caretakers of infants.

Long-Term Outcomes After Autologous Intestinal Reconstructive Surgery in Children With Short Bowel Syndrome.

OBJECTIVES: Autologous intestinal reconstructive (AIR) surgery is frequently utilized in the management of pediatric short bowel syndrome (SBS). However, little is known about the long-term sequela of these procedures. METHODS: We undertook a retrospective follow-up study addressing parenteral nutrition (PN) dependence, nutritional status, intestinal morbidity, and related complications in SBS patients having undergone AIR surgery (SBS-AIR, n = 19). We compared results with conservatively treated control SBS patients (SBS-C, n = 45). Eligible patients were identified from our institutional intestinal failure registry during 1985-2019. RESULTS: After median 11.4 follow-up years, 42% of SBS-AIR patients received PN in relation to 36% in SBS-C group ( P = 0.6210), and overall PN duration was significantly longer (35.4 vs 10 months, P = 0.0004) in SBS-AIR group. Although symptoms of intestinal dysfunction improved in majority (62%) of patients after AIR surgery, their symptoms remained more frequent and severe at latest follow-up compared to SBS-C group (39% vs 5%, P = 0.0015). Although bacterial overgrowth was more frequent in SBS-AIR group (53% vs 24%, P = 0.0416), latest endoscopy findings and fecal calprotectin levels as well as occurrence of anastomotic/staple line ulcerations were comparable between groups. Histological liver steatosis (50% vs 18%, P = 0.042) and impaired bone health (26% vs 6.7%, P = 0.042) were more frequent in SBS-AIR patients. CONCLUSIONS: While AIR surgery improved gastrointestinal symptoms and transition to enteral autonomy in majority of patients, a noteworthy proportion of them continued to suffer from clinically significant intestinal dysfunction and related complications. Close long-term follow-up of pediatric AIR surgery patients is mandatory.

Cutoffs and Characteristics of Abnormal Bowel Dilatation in Pediatric Short Bowel Syndrome.

OBJECTIVES: Although excessive intestinal dilatation associates with worsened outcomes in pediatric short bowel syndrome (SBS), little is known about the natural history and definition of pathological dilatation. We addressed fore-, mid-, and hind-gut dilatation in children with SBS, who had not undergone autologous intestinal reconstructive (AIR) surgery, in relation to controls. METHODS: SBS children without history of AIR surgery (n = 59) and age-matched controls without any disclosed intestinal pathology (n = 140) were included. Maximum diameter of duodenum, small bowel (SB), and colon were measured in each intestinal contrast series during 2002 to 2020 and expressed as diameter ratio (DR) to L5 vertebrae height. Predictive ability of DR for weaning off parenteral nutrition (PN) was analyzed with Cox proportional hazards regression models using multiple cutoffs. RESULTS: Duodenum (DDR), SB (SBDR), and colon (CDR) DR were 53%, 183%, and 23% higher in SBS patients compared to controls ( P < 0.01 for all). The maximal DDR and SBDR measured during follow-up is associated with current PN dependence and young age. DDR correlated with SBDR ( r = 0.586, P < 0.01). Patients with maximal DDR less than 1.5, which was also the 99th percentile for controls, were 2.5-fold more likely to wean off PN ( P = 0.005), whereas SBDR and CDR were not predictive for PN duration. CONCLUSIONS: All segments of remaining bowel, especially SB, dilate above normal levels in children with SBS. In SBS children without AIR surgery, PN dependence and young age is associated with duodenal and small intestinal dilatation, while duodenal dilatation also predicted prolonged PN.

Pediatric Short Bowel Syndrome: Real-World Evidence on Incidence and Hospital Resource Use From a Finnish Data Lake.

OBJECTIVES: Little is known about the epidemiology and healthcare burden of pediatric intestinal failure (IF). We aimed to assess the incidence, prevalence, healthcare resource utilization (HCRU), and related costs of pediatric short bowel syndrome (SBS) using follow-up data from the largest hospital district in Finland. METHODS: This retrospective registry study utilized electronic healthcare data covering all pediatric patients with SBS-IF born between 2010 and 2019 at the Hospital District of Helsinki and Uusimaa in Finland. Patients were followed from birth until the end of 2020 and compared to control patients, all from the same hospital system. RESULTS: In total, 38 patients with SBS-IF and 1:5 matched controls were included, with median follow-up time of almost 6 years from birth. Over half of the patients were born early preterm (gestational age ≤30 weeks). The incidence of pediatric SBS-IF was 24 per 100,000 live births. The HCRU was higher compared to controls and most of the inpatient days incurred during the first year of the SBS-IF patients' life. The average hospital-based HCRU costs were €221,000 for the first year and €57,000 for whole follow-up annually. The costs were higher for the early preterm patients and accumulated mainly from inpatient days. CONCLUSIONS: SBS-IF is a rare disease with a relatively low number of patients treated at each hospital district. The burden on the hospital system, as well as the patient's family, is especially high at the onset as the newborns with SBS-IF spend a significant part of their first year of life in the hospital.

Infant liver biochemistry is different than current laboratory accepted norms.

The purpose is to study liver biochemistry in a well-defined cohort of term infants. The methods include healthy term infants (n = 619) provided blood samples at 3 and 6 months of age when participating to the DIABIMMUNE study. The infants were followed up at clinical study visits 3, 6, 12, 18, 24, and 36 months the participation rate being 88.6% at the end of follow-up, while none disclosed any signs of a liver disease. The serum levels of serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), gamma-glutamyl transferase (GGT), total bilirubin (BIL), and conjugated bilirubin (BIL-conj) were determined using Siemens Atellica CH 930 analyzers. The results are at 3 months of age, the upper 90% CI for ALT, AST, ALP, GGT, BIL, and BIL-conj were higher than the current upper reference limits in our accredited hospital laboratory. At 6 months, the upper 90% CIs for ALT had declined but was still higher than the cut-offs for a raised value. The upper 90% CI for AST remained as high as at 3 months, whereas ALP, BIL-conj, and GGT had decreased close to the current cut-offs. The type of feeding was associated with the levels of liver biochemistry. Exclusively or partially breastfed infants showed higher ALT, AST, BIL, and BIL-conj values at 3 months than formula-fed. Breastfed infants had higher AST, Bil, and Bil-conj values also at 6 months.  Conclusion: We encourage setting appropriate reference ranges for liver biochemistry for the first year of life and to note the type of feeding. What is Known: • Healthy infants may show higher values of liver biochemistry during their first year of life than in later life. • It has been speculated that type of feeding may play a role in liver biochemistry levels among infants. What is New: • In a cohort of healthy infants, several analytes of liver biochemistry were higher than the currently used upper reference limits at 3 and 6 months of age, and exclusively or partially breastfed infants showed higher values than formula-fed. • The findings address the importance of setting appropriate reference ranges for liver biochemistry for the first year of life.

Therapy outcome related to adalimumab trough levels in pediatric patients with inflammatory bowel disease.

OBJECTIVES: We evaluated the relationship between serum concentration and efficacy of adalimumab (ADA), an anti-tumor necrosis factor-alpha agent, in pediatric patients with inflammatory bowel disease (PIBD). MATERIALS AND METHODS: This retrospective cross-sectional study traced 75 patients with PIBD (Crohn's disease, n = 57) treated with ADA at two tertiary centers in Finland in 2012-2018. Drug levels and drug antibody titers were chart-reviewed, and the treatment continuation rate of ADA therapy was evaluated. We also assessed the impact of trough levels in the first 3 months on the continuation of ADA within one year of therapy. RESULTS: ADA was introduced at a median age of 13.4 years, and the median disease duration was 2.7 years. During the first year, 22 patients (29%) discontinued ADA due to either loss of response (20%, n = 15) or anti-drug antibody formation (5.3%, n = 4). Regarding trough levels in the first 3 months, 9/16 patients (56%) with trough levels <5 mg/L and 12/20 (60%) with trough levels <7.5 mg/L at 3 months discontinued the therapy by the end of the first year. In comparison, only 8/32 patients (25%) with trough levels >7.5 mg/L at 3 months discontinued treatment during the first year (p = .005). At the last follow-up (median 1.5 years), 52% of the 75 patients were on maintenance therapy and had a median trough level of 8.8 mg/L. CONCLUSION: Higher trough levels in the first 3 months of adalimumab treatment are associated with lower rates of discontinuation due to loss of response during the first year.

Gastrointestinal symptoms and endoscopy findings after pediatric solid organ transplantation: A case series.

BACKGROUND: Gastrointestinal symptoms are common among solid organ transplant (SOT) recipients. Information about colonoscopy findings after pediatric SOT is limited. This retrospective study reports endoscopy findings in a nationwide pediatric transplant recipient cohort. METHODS: All pediatric recipients (kidney, liver, or heart) transplanted between 2010 and 2020 at our institution (n = 193) who had undergone ileocolonoscopy and upper gastrointestinal endoscopy after SOT were enrolled. Sixteen patients were identified. A meticulous search on clinical data including transplantation, gastrointestinal symptoms, endoscopy findings, and follow-up data was performed. RESULTS: Endoscopy was performed at a median of 2.6 years (0.4-13.3) after the first transplantation (median age at SOT 1.2 years). Gastrointestinal symptoms leading to endoscopy did not differ between the different transplant groups. The leading endoscopy indications were prolonged diarrhea and anemia. PTLD was found in 8 (50%) patients. Five were histologically early PTLD lesions and three were monomorphic large B-cell PTLDs (two EBV-positive and one EBV-negative), one having previously been diagnosed with autoimmune enteropathy. One patient had EBV enteritis. De novo inflammatory bowel disease was found in one patient, eosinophilic gastroenteritis in another, and in one patient with several episodes of watery diarrhea, the histological finding was mild non-specific colitis. In four patients, the endoscopy finding remained unclear and the symptoms were suspected to be caused by infectious agents or mycophenolate. CONCLUSIONS: PTDL with various stages is a common finding after pediatric SOT in patients with gastrointestinal symptoms. Endoscopy should be considered in transplant recipients with prolonged diarrhea, anemia, and/or abdominal pain.

Parentally reported early childhood upper gastrointestinal symptoms alleviate at school age.

AIM: This study estimated follow-up outcomes for children presenting with troublesome upper gastrointestinal (GI) symptoms in early childhood. METHODS: We identified from our upper endoscopy registry children with undefined GI symptoms having undergone an oesophagogastroduodenoscopy to rule out oesophagitis at a median age of 2.6 years in 2006-2016. We included only those with normal findings. In early 2020, we performed a National Patient Data Repository and Prescription Service review to note patients' current GI symptoms, medications and medical consultations. We also employed a study-specific questionnaire with a validated quality-of-life measure (the PedsQL). RESULTS: After a median of 7.9 years of follow-up, the children (n = 199) had a median age of 10.6 years. Medical consultations related to upper GI symptoms were rare. However, parents reported recurrent GI symptoms in 24% of the children, and 41% followed a specific diet. Regular anti-acid medication was in use in 3.5% of the cohort, more often when with a predisposing condition for reflux disease. The current quality of life was good. CONCLUSION: Although some upper GI symptoms may persist after early childhood, patients without diseases predisposing to reflux disease have a good quality of life without GI-related morbidity in school age.

Prediction, identification and progression of histopathological liver disease activity in children with intestinal failure.

BACKGROUND & AIMS: Diagnostic criteria, progression risk and optimal monitoring for intestinal failure (IF)-associated liver disease (IFALD) remain undefined. We assessed predictors, non-invasive markers and progression of histopathological liver disease in patients with IF. METHODS: In total, 77 children with IF and median age of 1.7 years underwent diagnostic liver biopsy, which was repeated in 48 patients after 2.9 years with simultaneous evaluation of liver biochemistry, liver stiffness, serum citrulline (a surrogate for viable enterocyte mass), spleen size, esophageal varices and clinical data. Patients were staged according to histopathological liver disease activity: active IFALD (cholestasis and/or inflammation), chronic IFALD (significant fibrosis and/or steatosis), or no IFALD (none of these features). RESULTS: Diagnostic liver biopsy revealed active, chronic or no IFALD in 48%, 21% and 31% of patients. Active IFALD was segregated by low serum citrulline, parenteral nutrition (PN) dependency and young age, while weaning off PN and older age predicted chronic IFALD. Although the liver histopathology in most patients either normalized (52%) or transformed to a less reactive (chronic) disease stage (23%), 19% of patients retained and 6.3% progressed to an active cholestatic/inflammatory IFALD phenotype. Decreased serum citrulline and PN-dependency also predicted active IFALD in follow-up biopsies. Increased median liver biochemistry values and liver stiffness only associated with active IFALD, which was accurately identified by gamma-glutamyltransferase (GGT), citrulline and liver stiffness, their combinations reaching diagnostic and follow-up AUROC values above 0.90. CONCLUSIONS: Active IFALD, essentially predicted by intestinal disruption and PN-dependency, was accurately detected by GGT, liver stiffness and citrulline, which together with recent advances in clinical management options, provides new avenues for monitoring and targeted liver protection in patients with IF. LAY SUMMARY: Liver disease is a common and critical complication in patients with intestinal failure, who require intravenous nutrition for survival due to severe intestinal dysfunction. We showed that both intravenous nutrition dependency and intestinal disruption essentially predicted development of active histopathological liver disease, which persisted in 25% of patients during long-term follow-up and could be accurately detected without the need for liver biopsy. Identification of the active and potentially progressive histopathology offers new possibilities for monitoring and targeted liver protection in patients with intestinal failure.

Neonatal Intestinal Failure Is Independently Associated With Impaired Cognitive Development Later in Childhood.

OBJECTIVE: The impact of pediatric intestinal failure (IF) on neurodevelopment beyond infancy has not been systematically studied. Our aim was to evaluate cognitive and motor impairment and to identify risk factors for adverse outcomes among children with IF. METHODS: We conducted a cross-sectional single-center study at the Helsinki University Children's Hospital. Patients with IF with >60 days of parental nutrition (PN) dependency aged between 3 and 16 years (n = 40) were invited to participate. The cognitive and motor skills were evaluated using validated tests: Wechsler Preschool and Primary Scale of Intelligence, 3rd edition, Wechsler Intelligence Scale for Children, 4th edition, and Movement Assessment Battery for Children, 2nd edition. RESULTS: All the patients attending the study tests (n = 30, males = 24) were included. Their median age, gestational age, and birth weight was 7.5 (range 3-16) years, 35 (interquartile range [IQR] 28-38) weeks and 2238 (IQR 1040-3288) grams, respectively. Median duration of PN was 13 (IQR 5-37) months and 9 patients were currently on PN. Median intelligence quotient was 78 (IQR 65-91) and 10 (35%) patients had an intelligence quotient under 70 (-2 standard deviation). Significant motor impairment was detected in 10 patients (36%) and milder difficulties in 8 (28%). Adverse cognitive outcome was associated with neonatal short bowel syndrome, number of interventions under general anesthesia, and length of inpatient status, whereas adverse motor outcome was associated with prematurity. CONCLUSION: Clinically significant cognitive and motor impairments are alarmingly common among neonatal patients with IF. We recommend early neurodevelopmental follow-up for all children with IF.

Upper endoscopy for non-acute non-specific symptoms is seldom beneficial for children under the age of seven.

AIM: This study estimated the diagnostic yield of oesophagogastroduodenoscopy (OGD) in young children with non-acute, non-specific gastrointestinal or respiratory symptoms who were treated by a Finnish tertiary level referral centre. METHODS: A retrospective chart analysis was performed on 1850 Finnish children under 7 years of age who underwent their first diagnostic OGDs at Helsinki University Hospital during 2006-2016. We noted the endoscopy indications, macroscopic findings, the histology of the mucosal biopsies and the follow-up data. RESULTS: After the exclusion criteria were applied, we enrolled 666 patients (57.7% boys) at a median age of 3.5 years. The number of children with non-specific symptoms referred for OGD increased 2.3-fold in 11 years. A routine set of biopsies was obtained in 644/666 (96.7%) of the endoscopies. The OGD was both macroscopically and histologically normal in 519/644 (80.6%) of cases. The most common indication was to rule out gastro-oesophageal reflux disease in 268/666 (40.2%) cases, and the most frequent histological diagnosis was mild to moderate oesophagitis in 57/644 (8.9%) cases. There was no erosive oesophagitis. CONCLUSION: The diagnostic yield of macroscopic and histological OGD findings was low in our cohort. Unless there are alarming symptoms, younger children do not need OGD.

Gastrointestinal Symptoms of Food Challenge-proven Non-IgE Cow's Milk Allergy Are Dissipated by Early School Age.

OBJECTIVES: The aim of this study was to evaluate the current well-being and dietary restrictions in children 6 years after food challenge-confirmed diagnosis of non-IgE cow's milk protein allergy, compared to peers with gastrointestinal symptoms but negative food challenge. This study aimed to evaluate the diagnostic process retrospectively. METHODS: This is an Internet-based survey for mothers whose children underwent 6 years ago the double-blind, placebo-controlled food challenge for cow's milk (CM) because of gastrointestinal symptoms causing suspicion of non-IgE CM protein allergy. Concurrent dietary restrictions, overall well-being, medical history, and retrospective views on the food challenge were queried using a study-specific questionnaire, the Quality of life using PedsQL general score and parental stress with the Parenting Stress Index questionnaire. RESULT: Mothers of 42 children (23 girls), median age of 6.7 years (range 5.7-8.6), participated in the survey, the response rate was 70%. All children now consumed cow's milk protein. The only food restrictions reported were empirical lactose-free diets in 7 children (17%). One-third of the children in both groups were presently reported to have eating-related issues such as picky eating. Quality of life was good and present parenting stress was average in both groups. The majority of the mothers (87%) felt positive or neutral about the food challenge performed in infancy. CONCLUSIONS: The non-IgE CM allergy with gastrointestinal symptoms diagnosed in infancy was a transient condition with good outcome. At an early school age, nearly all children have a good quality of life and a regular diet. The use of the double-blind, placebo-controlled food challenge was well-endorsed.

Fecal Calprotectin Test Performed at Home: A Prospective Study of Pediatric Patients With Inflammatory Bowel Disease.

OBJECTIVES: Measuring fecal calprotectin (FC) in a laboratory is time-consuming and that is why home tests have been developed. We studied the use of an FC home test in pediatric patients with inflammatory bowel disease (PIBD) in real-life settings. METHODS: The patients were asked to perform the IBDoc FC home test monthly for 6 months and to report their clinical disease activity at testing. Clinical decision-making, however, was guided by routine FC enzyme-linked immunosorbent assay (ELISA) for patients with raised IBDoc values. Spare frozen samples were analyzed using ELISA and IBDoc in the laboratory. The participants completed a questionnaire about FC testing at the start and end of the study. RESULTS: Of the 52 patients, 35 (67%) ages 5 to 18 years completed the study, and 197 home tests were performed. Of these, 15% failed, mainly because of technical reasons. Just under half of the patients (47%) considered home testing comparable or superior to routine testing. In contrast, the parents were unsatisfied (61%), mostly because the IBDoc results were significantly different from ELISA and they found the phone application difficult to handle but whenever the IBDoc was performed by a laboratory professional it was comparable with ELISA, suggesting that practical issues hampered home testing. Despite their reservations, more than 80% of parents felt that home testing would improve disease management. CONCLUSIONS: PIBD patients and their families were interested in FC home monitoring and willing to adopt testing as a part of their disease management, but this approach requires thorough guidance.

Small Bowel Dilatation Predicts Prolonged Parenteral Nutrition and Decreased Survival in Pediatric Short Bowel Syndrome.

OBJECTIVE: To analyze risk factors and prognostic significance of small bowel (SB) dilatation in children with short bowel syndrome (SBS). BACKGROUND: In SBS, the remaining SB may dilate as part of intestinal adaptation. The impact of dilatation on parenteral nutrition (PN) dependence and survival has not been studied systematically. METHODS: SB diameter of SBS children (n = 61) was measured in contrast SB series (n = 169, median age 0.94, range 0.32-2.7 years) during 2002 to 2015, and expressed as millimeters (SB width) and as ratio to L5 vertebra height (SB diameter ratio). Linear regression was used to examine risk factors for dilatation. PN weaning and survival were analyzed with Cox proportional hazards regression. RESULTS: Maximal SB diameter ratio during follow-up was predicted by PN dependence and SB atresia, while maximal absolute SB width by birth weight, age, PN duration, and remaining bowel length. Weaning off PN was 14-fold more likely in patients with maximal SB diameter ratio <2.00 compared with >3.00 (P = 0.005), and 5.4-fold more likely when maximal SB width was <20 mm compared with >30 mm (P = 0.023). After adjustment for age, remaining SB length, and the presence of ileocecal valve, both estimates of maximal SB dilatation remained significant independent predictors for weaning off PN. When all measurements were included, the cumulative survival was worse if SB diameter ratio exceeded 2.00 (P = 0.002-0.042). CONCLUSIONS: SB dilatation predicts prolonged PN duration and decreased survival in SBS children. Measurement of maximal SB diameter standardized to L5 vertebra height may be a valuable objective tool for patient follow-up and assessment of prognosis.

Clinical Use of Infliximab Trough Levels and Antibodies to Infliximab in Pediatric Patients With Inflammatory Bowel Disease.

OBJECTIVES: Optimizing infliximab (IFX) treatment in pediatric patients with inflammatory bowel disease (IBD) by using serum infliximab (S-IFX) trough levels and antibodies to IFX is recommended. There is need for studies assessing this strategy in clinical practice. METHODS: We retrospectively identified all pediatric patients with IBD (n = 146, median age 14.8 years) treated with IFX at our tertiary referral center from 2003 to 2014. All were analyzed for IFX trough levels (S-IFX, n = 475), and IFX antibody (IFX-Ab, n = 219) titers were included. Both were analyzed using enzyme-linked immunosorbent assay. We correlated these parameters with concurrently analyzed fecal calprotectin levels and the treatment outcome. RESULTS: If IFX had no efficacy, or a loss of response occurred, 40 of 64 (63%) had trough levels <2.0 mg/L, with negative IFX-Ab in 37 of 59 (63%). If the S-IFX was very low (<0.2 mg/L), 4 of 36 still had negative IFX-Ab. Concurrent azathioprine therapy did not relate to IFX-Ab. Fecal calprotectin was significantly lower in patients with clinical remission or ongoing therapy compared with those with subsequent loss of efficacy: medians 95 µg/g (33-308) and 670 µg/g (264-1473), P < 0.0001. The S-IFX median was substantially higher in patients with either remission or ongoing therapy, compared with those with no or loss of efficacy: 3.7 mg/L (1.8-5.4) and 1.2 mg/L (0.03-4.4, P = 0.01), respectively. CONCLUSIONS: Measuring IFX trough levels and fecal calprotectin has a potential impact on the treatment strategies and should be included in clinical routine. Low IFX trough levels associate with increased antibodies to IFX in most, but not in all cases.

Duodenal Disaccharidase Activities During and After Weaning off Parenteral Nutrition in Pediatric Intestinal Failure.

OBJECTIVES: Data on factors affecting absorptive function in children with intestinal failure (IF) are sparse. We evaluated duodenal disaccharidase activities and inflammation in relation to parenteral nutrition (PN) and intestinal resection in pediatric onset IF. METHODS: Disaccharidase (maltase, sucrase, and lactase) activities and histologic inflammation were evaluated from duodenal biopsies in 58 patients during PN (n = 23) or full enteral nutrition (n = 40) and in 43 matched controls. The first and the last postresection biopsies were analyzed separately after 4.3 (1.2-9.7) years and 6.5 (2.3-12.4) years, respectively. RESULTS: During PN, maltase and sucrase activities were 1.6-fold lower and mucosal inflammation more frequent (22% vs 3%) when compared to matched controls (P < 0.05 for both). In patients on full enteral nutrition, activities of maltase and sucrase were significantly higher than that in patients receiving PN and comparable to those of matched controls. Postresection time correlated positively (r = 0.448 and r = 0.369) and percentage length of the remaining small intestine inversely (r = -0.337 and r = -0.407) with maltase and sucrase activity in patients on full enteral nutrition (P < 0.05 for all), whereas proportional length of remaining colon correlated positively with maltase and lactase activity (r = 0.424-0.544, P < 0.05) in patients receiving PN. CONCLUSIONS: In children with IF, PN dependency associated with decreased duodenal maltase and sucrase activities and mucosal inflammation, which may disturb intestinal absorptive function. Localization and extent of intestinal resection and post-resection time correlated with duodenal disaccharidase activities.

Transient elastography and aspartate aminotransferase to platelet ratio predict liver injury in paediatric intestinal failure.

BACKGROUND & AIMS: We aimed to evaluate the value of AST to platelet ratio (APRI) and transient elastography (TE) as predictors of liver histopathology in children with intestinal failure (IF). METHODS: Altogether 93 liver biopsies from 57 children with parenteral nutrition (PN) duration ≥3 months were analysed. APRI measurement and TE (n = 46) were performed at the time of biopsy. RESULTS: IF was caused by short bowel syndrome in 75% of patients. At the time of liver biopsy, PN dependent patients (n = 42) were younger with longer PN duration compared to those weaned off PN (n = 51) (2.2 vs. 7.6 years, P < 0.001; 26 vs. 10.5 months, P = 0.043). Elevated transaminase or bilirubin levels were found in 51%, splenomegaly in 26%, and oesophageal varices in 3.5%. Histological fibrosis was present in 61% (Metavir stage F1; 27%, F2; 26%, F3-4; 9%), cholestasis in 25% and steatosis in 22% of biopsy specimens. TE was superior to APRI in prediction of any liver histopathology (fibrosis, cholestasis or steatosis) with areas under the receiving operating curve (AUROC) of 0.86 (95% CI 0.74-0.97) and 0.67 (95% CI 0.58-0.78) respectively. For prediction of ≥F1 and ≥F2 fibrosis, AUROC values for TE were 0.78 (95% CI 0.64-0.93) and 0.73 (95% CI 0.59-0.88), whereas APRI did not correlate with fibrosis stages. For detection of histological cholestasis, the AUROC for APRI was 0.77 (95% CI 0.64-0.89). CONCLUSIONS: Both TE and APRI are promising noninvasive methods for monitoring the development of IF-related liver histopathology. TE values reflected the degree of fibrosis better while APRI detected histological cholestasis more accurately.