Bruno Pedro Chumpitazi

Introduction: Although pain is recognized as an important symptom in gastroparesis, it has not been well studied and characterized. Quantitative sensory testing (QST) is a psychophysical method that has the potential to provide a measure of pain processing, as well as insight into pain pathophysiology and the prediction of response to specific therapies. We aimed to characterize somatic QST in a well‐characterized cohort of patients with gastroparesis. Methods: Adults with scintigraphically defined gastroparesis underwent abdominal QST with assessment of mechanical pain: pain sensitivity (thresholds and tolerance) and pain facilitation (temporal summation). The Patient Assessment of Upper GI Symptoms (PAGI‐SYM) upper and lower abdominal pain scales were used. Results: QST was performed on 264 participants (87% female; age = 18–78 years). In both the upper and lower abdomen, smaller pain thresholds and lower pain tolerance were significantly associated with greater PAGI‐SYM upper abdominal pain severity ( b 's = 0.07–0.15; p 's = 0.007–0.02), but not lower abdominal pain severity. Scores on the PAGI‐SYM upper and lower abdominal pain scales were moderately correlated ( r = 0.48, p < 0.0001). No significant associations were found for temporal summation. Conclusions: Our findings suggest self‐reported upper abdominal pain severity correlated with both lower and upper abdominal mechanical pain sensitivity—possibly reflecting secondary sensitization of the abdominal wall, due to viscerosomatic convergence in upper abdominal somatic segments. Lower abdominal pain severity association with only upper (but not lower) abdominal QST may be due to cross‐organ sensitization. Further investigations are needed to test the clinical utility of abdominal QST in gastric sensorimotor disorders. Trial Registration: ClinicalTrials.gov : NCT01696747

Introduction: Meal‐related symptoms are commonly identified in disorders of gut–brain interaction (DGBIs). Gastroduodenal low‐grade inflammation involving mucosal eosinophils and/or mast cells has been previously described in patients with DGBIs. In children with DGBIs, we sought to determine potential relationships between gastric and duodenal mucosal eosinophils and mast cells with specific meal‐related and non‐GI somatic symptoms. Methods: Two hundred eight youth with AP‐DGBI were evaluated. All patients underwent esophagogastroduodenoscopy (EGD) with biopsies taken from the gastric antrum and duodenum. Patients completed symptom and BASC‐3 questionnaires to evaluate somatization and the presence of specific meal‐related and non‐GI somatic symptoms. A single observer blinded to clinical data reported maximum density of eosinophils and mast cells. Key Results: Mucosal eosinophil and mast cell counts did not differ between FD and IBS nor between FD subtypes. After correction for multiple comparisons, there were no associations between eosinophil or mast cell counts with meal‐related symptoms. In contrast, duodenal mast cells were positively associated with headaches, dizziness, fatigue, and rhinitis, with predominantly medium effect sizes. Conclusions and Inferences: Meal‐related symptoms are common in youth with DGBIs, but do not appear to be associated with mucosal eosinophils and mast cell counts. The positive associations of duodenal mast cells with non‐GI somatic complaints suggest future studies should determine whether treatments targeting mast cells are beneficial for ameliorating these symptoms in youth with DGBIs.

Introduction: Many children with abdominal pain‐associated disorders of gut‐brain interaction (AP‐DGBI) have meal‐related symptoms. The aim of the current study was to determine if meal‐related symptoms defined specific mutually exclusive subgroups (classes) and, if so, whether these relate to other pathophysiologic factors. Methods: Between 2020 and 2022, 289 children with AP‐DGBI completed questionnaires evaluating gastrointestinal symptoms, psychosocial variables (e.g., somatization), and health‐related quality of life (HRQoL). Latent class analysis (LCA) evaluated symptom patterns using 10 gastrointestinal symptoms, while univariable latent class regression (LCR) analyzed associations with covariates. Key Results: Three latent classes emerged: Class 1 (characterized by low meal‐ and stool‐related symptom burden, 35.0%), Class 2 (exhibiting meal‐related symptoms, 32.2%), and Class 3 (manifesting meal‐ and stool‐related symptoms, 32.8%). Compared to Class 1, odds of belonging to Class 2 were significantly associated with increasing age, female sex, and lower HRQoL in physical and school functioning. Compared to Class 1, odds of belonging to Class 3 were similarly associated with increasing age, female sex, somatization, and with reduced HRQoL in physical, social, and psychosocial domains. There were no group differences with respect to depression, social stress, or anxiety. Conclusions and Inferences: In youth with AP‐DGBI, three distinct phenotypic groups are identified. Two of these distinct groups experience meal‐related symptoms: one with associated bowel symptoms and the other without. These two meal‐related symptom groups are associated with increasing age, female sex, somatization, and reduced HRQoL (particularly physical). These findings underscore the distinctness and importance of identifying the drivers of meal‐related symptoms in children with AP‐DGBI.

Background: Patients with gastroparesis (Gp) can have a variety of symptoms. Apart from use of prokinetics, symptomatic therapies for the predominant symptom (PrS) are used. Aims: (1) To classify Gp patients based on their PrS; (2) To determine differences in Gp symptoms, gastric emptying (GE), quality of life (QOL), treatments, and symptom improvement among Gp patients with different PrS. Methods: Gp patients were enrolled in a multicenter registry and followed for 96‐weeks. Patients recorded their PrS and completed questionnaires assessing symptoms and QOL at enrollment and at follow up visits. Results: Of 1013 Gp patients (361 diabetic, 607 idiopathic, 45 post‐fundoplication), the PrS were nausea (31%), vomiting (20%), abdominal pain (20%), bloating (9%), fullness (4%), GERD (4%), constipation (3%). Abdominal pain was more often a PrS in idiopathics, whereas vomiting was more often a PrS in diabetics. QOL scores were lower in the abdominal pain PrS group. PrS was associated with greater use of directed symptomatic treatment (antiemetic agents and gastric electrical stimulation for nausea and vomiting, prokinetic agents for vomiting and fullness, and constipation medications for constipation). Of 555 patients followed over 48 weeks, GCSI improved by ≥ 1 in 26% overall, more often in patients with initial PrS of nausea (32%) and bloating (35%) and less often for initial PrS of fullness (13%) or abdominal pain (15%). Conclusions: In Gp patients, the most common PrS were nausea, vomiting, and abdominal pain. PrS is associated with QOL, treatments utilized, and patient outcomes. Thus, the PrS of a patient with Gp provides useful information about their present condition and future outcome.

INTRODUCTION: Autism is associated with gastrointestinal problems; however, contemporary data on constipation prevalence and healthcare utilization are lacking. METHODS: We queried >20 million electronic records of youth 6–17 years from 70 Patient-Centered Outcomes Research Network health systems during 2015–2024, identifying diagnoses of autism, constipation, emergency department visits, and hospitalizations. RESULTS: Among 578,807 autistic children, 22% had constipation vs 9% in nonautistic youth. Autistic children with constipation (vs without) had more frequent abdominal pain (34% vs 8%), emergency department visits (26% vs 3%), and hospitalizations for abdominal pain/constipation (16% vs 1%). DISCUSSION: Approximately 1 in 5 autistic children have constipation and experience high unplanned healthcare utilization.

Pediatric neurogastroenterology conditions, including disorders of gut-brain interaction (DGBI) and motility disorders, affect millions of children worldwide. Due to limited pediatric data, reference ranges and management are often extrapolated from adult studies. We review four pediatric neurogastroenterology areas where clinical science may translate and inform adult gastroenterology. Sucrase-isomaltase deficiency can be diagnosed via disaccharidase enzyme testing from duodenal mucosal biopsies. Dietary restriction and sacrosidase supplementation are effective, based on randomized controlled trials, in children with genetic sucrase-isomaltase deficiency; however, they remain to be rigorously studied in adults. Gastric emptying breath testing (GEBT) in large cohorts of children reinforces the importance of biological sex, puberty, and size while deriving normative reference values. Further study of GEBT in adults may help determine the influence of sex and hormones on gastric emptying rates, offering an opportunity to develop tailored reference ranges. Antegrade continence enema (ACE) therapy is the most common reversible surgical treatment for children with chronic constipation with high rates of efficacy. Few studies have investigated the efficacy of ACE in adult populations. Auricular neurostimulation through percutaneous electrical nerve field stimulation is Food and Drug Administration approved for use in adolescents with irritable bowel syndrome and functional dyspepsia based on sham-controlled, randomized trials with emerging efficacy data in other pediatric DGBI. To date, efficacy studies using auricular neurostimulation in adults with gastrointestinal disorders have not been performed. These areas highlight how pediatric neurogastroenterology generates discoveries with the potential to guide approaches in adult populations, underscoring the bidirectional value of translational clinical science.

INTRODUCTION: Diagnosing pediatric gastroparesis presents a significant challenge due to lack of normative data in children. We aimed to determine normative values for gastric emptying using the nonradioactive ¹³ C-Spirulina gastric emptying breath test ( ¹³ C-GEBT) in a large cohort of healthy children (HC) and examine differences compared to children with gastroparesis-like symptoms (GLS). METHODS: A total of 301 HC ages 7–18 years completed the ¹³ C-GEBT with 10 different breath samples × 4 hours. ¹³ CO ₂ excretion rate (kPCD) was determined by change in ¹³ CO ₂ / ¹² CO ₂ . Outcome variables included: kPCD at 10 time points, peak (maximum) kPCD, time to peak (T _max ) kPCD, and area under curve (AUC) of ¹³ CO ₂ excretion, along with breath test half emptying time (BT t _½ ). Results were compared with ¹³ C-GEBT data from peripubertal and postpubertal patients 11–18 years of age with GLS. RESULTS: A total of 216 HC, 51.4% female, completed the test meal within the allotted time. Females vs. males had lower peak kPCD ( P = 0.003), longer T _max ( P = 0.04), lower AUC ( P < 0.001), and longer BT_t _½ ( P < 0.0001). Peak kPCD ( P = 0.01, P < 0.001) and AUC ( P = 0.012, P < 0.001) were higher in prepubertal vs peri pubertal and postpubertal children. BT_t _½ and T _max were shorter in HC vs. GLS ( P < 0.001, P < 0.0001, respectively), consistent with faster gastric emptying in HC. Normative reference values based on 5th percentile kPCD and T _max were established for peripubertal and postpubertal females. An algorithm incorporating key variables demonstrated 80.8% sensitivity for diagnosis of gastroparesis. DISCUSSION: This study demonstrates sex and pubertal differences in gastric emptying in children and provides the first reference values for female children.

Objectives: Restricting dietary fermentable oligosaccharides, disaccharides, monosaccharides, and polyols (FODMAPs) can alleviate symptoms in children with disorders of gut-brain interaction (DGBI). Due to the restrictions of a low FODMAP diet (LFD), a less restrictive FODMAP Gentle diet (FGD) has been suggested. However, the types and amounts of high FODMAP foods and carbohydrates commonly consumed by children have not been studied. We aimed to identify the high FODMAP foods and proportions of FODMAP carbohydrates consumed by children with DGBI and healthy children (HC) and to determine which usually ingested FODMAPs would be restricted on the FGD. Methods: Three-day diet records from both children with DGBI and HC were analyzed and compared to assess the type and amount of high FODMAP foods and carbohydrates ingested. Additionally, the ingested FODMAPs that would be restricted on the FGD were determined. Results: Diet records from 77 children with DGBI and 64 HC were analyzed. The number of foods ingested daily was similar between children with DGBI and HC (12.3 ± 4.2 vs 12.9 ± 3.4, respectively); high FODMAP foods comprised most foods eaten in both groups. Children with DGBI (vs. HC) ate fewer high FODMAP foods per day (6.5 ± 2.3 vs 8.7 ± 2.4, P < 0.0001, respectively). Fructans were the most consumed FODMAP carbohydrate in both groups, and children with DGBI (vs. HC) consumed fewer fructans, lactose, fructose, and polyols (all P < 0.0001). The top 3 food categories consumed in both groups were wheat-containing foods, dairy, and fruits/ 100% fruit juices. In children with DGBI, 80.9% of the high FODMAP foods consumed would be limited on the FGD. Conclusions: Children with DGBI consume fewer high FODMAP foods and carbohydrates than HC, with the top consumed FODMAP carbohydrates being fructans, lactose, and fructose. A FGD would restrict most high FODMAP foods consumed by children with DGBI.

Background/Objectives: Disorders of gut–brain interaction (DGBI), characterized by chronic abdominal pain and significant disability, affect 15–20% of children and adults and continue into adulthood in ~60% of cases. Costs for adults reach USD 30 billion per year, yet effective management strategies are elusive. Studies support using cognitive behavioral therapy (CBT), but abdominal pain only improves in ~40% of patients. Dietary management (low FODMAP diet; LFD) has also shown promise but it is effective in only a similar percentage of patients. Studies suggest that biologic factors (biomarkers) contribute to CBT response. Similarly, gut microbiome composition appears to influence abdominal pain response to the LFD. However, no previous CBT trials in children or adults have measured these biomarkers, and it is unclear which patients respond best to CBT vs. LFD. Methods: Children aged 7–12 years with DGBIs (n = 200) will be categorized as having/not having Autonomic Nervous System imbalance and/or abnormalities in gut physiology. We will randomize these children to either CBT or a LFD to compare the effectiveness of these treatments in those with/without abnormal physiologic biomarkers. We hypothesize that CBT will be more effective in those without abnormal physiology and LFD will be more effective in children with abnormal physiology. Primary outcome measures include the following: (1) Symptom improvement (abdominal pain frequency/severity) and (2) improvement in health-related quality of life. Conclusions: This innovative multidisciplinary study is the first to identify physiological characteristics that may moderate the response to two different management strategies. Identification of these characteristics may reduce the burden of these disorders through timely application of the intervention most likely to benefit an individual patient.