Optimal measurement of gastric emptying of solids in gastroparesis or functional dyspepsia: evidence to establish standard test.

OBJECTIVE: Symptoms in gastroparesis (Gp) and functional dyspepsia (FD) overlap; using egg protein substitute to measure gastric emptying of solids (GES), ~40% of patients are reclassified from Gp to FD, and vice versa. Our aim was to assess inter-individual and intra-individual coefficients of variation (COV) in GES in symptomatic patients with Gp or FD with documented slow or normal GES, respectively. DESIGN: Scintigraphic GES (T1/2 and GE% at 2 and 4 hours) using a 320 kcal real egg meal (30% fat) was tested in the following: single measurements in 20 patients with diabetes mellitus (10 each type 1 and type 2); repeat GES to estimate COVintra measured: 3 days apart in 9 Gp, 4 weeks apart in 21 Gp and 18 with FD with normal GE assigned to placebo and in 70 patients at 94.3 weeks (median) apart. RESULTS: COVinter for GE% at 4 hours and GE T1/2 were respectively 14.2% and 23.5% in FD and 27.5% and 33% in Gp; COVintra for GE% at 4 hours and GE T1/2 up to 4 weeks apart were 23.4% and 37.9% in FD and 20.1% and 33% in Gp. GE% at 2 hours showed less consistent results. However, >85% retained original diagnosis as normal or delayed. From clinical GES to baseline research for Gp group, repeat GES (after treatment) showed the COVintra for GE% at 4 hours was 37.3% at median 94.3 weeks, with 26/70 changed diagnoses. CONCLUSION: The 320 kcal (30% fat) GES scintigraphic test provides consistent diagnosis in >85% and should be the standard test for suspected gastric emptying disorders.

A Randomized, Controlled Trial of Efficacy and Safety of Cannabidiol in Idiopathic and Diabetic Gastroparesis.

BACKGROUND & AIMS: Cannabis (delta-9-tetrahydrocannabinol), a nonselective cannabinoid-receptor agonist, relieves nausea and pain. Cannabidiol (CBD), a cannabinoid receptor 2 inverse agonist with central effects, also reduces gut sensation and inflammation. We compared the effects of 4 weeks of treatment with pharmaceutical CBD vs placebo in patients with idiopathic or diabetic (diabetes mellitus) gastroparesis. METHODS: We performed a randomized, double-blinded, placebo-controlled study of CBD twice daily (Epidiolex escalated to 20 mg/kg/d; Jazz Pharmaceuticals, Dublin, Ireland) in patients with nonsurgical gastroparesis with delayed gastric emptying of solids (GES). Symptoms were assessed by the Gastroparesis Cardinal Symptom Index Daily Diary. After 4 weeks of treatment, we measured GES, gastric volumes, and Ensure (Abbott Laboratories, Abbott Park, IL) satiation test (1 kcal/mL, 30 mL/min) to assess volume to comfortable fullness and maximum tolerance. Patients underwent specific FAAH and CNR1 genotyping. Statistical analysis compared 2 treatments using analysis of variance including baseline measurements and body mass index as covariates. RESULTS: Among 44 patients (32 idiopathic, 6 diabetes mellitus type 1, and 6 diabetes mellitus type 2), 5 patients did not tolerate full-dose escalation; 3 withdrew before completing 4 weeks of treatment (2 placebo, 1 CBD); 95% completed 4 weeks of treatment and diaries. Compared with placebo, CBD reduced the total Gastroparesis Cardinal Symptom Index score (P = .008), inability to finish a normal-sized meal (P = .029), number of vomiting episodes/24 hours (P = .006), and overall symptom severity (P = .034). Patients treated with CBD had a higher volume to comfortable fullness and maximum tolerance and slower GES. FAAH rs34420 genotype significantly impacted nutrient drink ingestion. The most common adverse events reported were diarrhea (14 patients), fatigue (8 patients), headache (8 patients), and nausea (7 patients). CONCLUSIONS: CBD provides symptom relief in patients with gastroparesis and improves the tolerance of liquid nutrient intake, despite slowing of GES. CLINICALTRIALS: gov NCT #03941288.

Comparison of biochemical, microbial and mucosal mRNA expression in bile acid diarrhoea and irritable bowel syndrome with diarrhoea.

OBJECTIVE: There are altered mucosal functions in irritable bowel syndrome with diarrhoea (IBS-D); ~30% of patients with IBS-D have abnormal bile acid (BA) metabolism (ABAM) and diarrhoea (summarised as BAD). AIM: To compare biochemical parameters, gastrointestinal and colonic transit, rectal sensation and pathobiological mechanisms in IBS-D without ABAM and in BAD (serum 7C4>52 ng/mL). DESIGN: In patients with Rome III criteria of IBS-D, we compared biochemical features, colonic transit, rectal sensation, deep genotype of five BA-related genes, ileal and colonic mucosal mRNA (differential expression (DE) analysis) and stool dysbiosis (including functional analysis of microbiome). Results in BAD were compared with IBS-D without ABAM. RESULTS: Compared with 161 patients with IBS-D without ABAM, 44 patients with BAD had significantly faster colonic transit, lower microbial alpha diversity, different compositional profile (beta diversity) and higher Firmicutes to Bacteroidetes ratio with evidence of decreased expression of bile acid thiol ligase (involved in transformation of primary to secondary BAs) and decreased sulfatases. In BAD (compared with IBS-D without ABAM), terminal ileal biopsies showed downregulation of SLC44A5 (a BA transporter), and ascending colon biopsies showed upregulation in barrier-weakening genes (CLDN2), serine protease inhibitors, immune activation, cellular differentiation and a cellular transporter (FABP6; BA binding). No DE of genes was documented in descending colon biopsies. The two groups had similar rectal sensation. CONCLUSION: Though sharing clinical symptoms with IBS-D, BAD is associated with biological differences and mechanisms that have potential to enhance diagnosis and treatment targeting barrier dysfunction, inflammatory and microbial changes.

Effects of liraglutide on gastrointestinal functions and weight in obesity: A randomized clinical and pharmacogenomic trial.

OBJECTIVE: This study aimed to determine the effects of a long-acting glucagon-like peptide-1 (GLP-1) receptor agonist, liraglutide, and placebo subcutaneously over 16 weeks on weight and gastric functions and to evaluate associations of single-nucleotide polymorphisms in GLP1R (rs6923761) and TCF7L2 (rs7903146) with effects of liraglutide. METHODS: The study conducted a randomized, parallel-group, placebo-controlled, 16-week trial of liraglutide, escalated to 3 mg subcutaneously daily in 136 otherwise healthy adults with obesity. Weight, gastric emptying of solids (GES), gastric volumes, satiation, and body composition measured at baseline and after treatment were compared in two treatment groups using analysis of covariance. RESULTS: Liraglutide (n = 59) and placebo (n = 65) groups completed treatment. Relative to placebo, liraglutide increased weight loss at 5 and 16 weeks (both p < 0.05), slowed time to half GES (T1/2 ) at 5 and 16 weeks (both p < 0.001), and increased fasting gastric volume (p = 0.01) and satiation (p < 0.01) at 16 weeks. GES T1/2 was positively correlated with weight loss on liraglutide (both p < 0.001). After 16 weeks of liraglutide, GLP1R rs6923761 (AG/AA vs. GG) was associated with reduced percent body fat (p = 0.062), and TCF7L2 rs7903146 (CC vs. CT/TT) was associated with lower body weight (p = 0.015). CONCLUSIONS: Liraglutide, 3 mg, induces weight loss with delay in GES T1/2 and reduces calorie intake. Slowing GES and variations in GLP1R and TCF7L2 are associated with liraglutide effects in obesity.

Clinical trial: a single-centre, randomised, controlled trial of tradipitant on satiation, gastric functions, and serum drug levels in healthy volunteers.

BACKGROUND: Tradipitant, an NK1 receptor antagonist, improved symptoms in patients with gastroparesis. It is unclear whether these effects are mediated centrally (e.g., vomiting centre) or on gastric functions. As a class, NK1 antagonists may retard gastric emptying (GE) or increase fasting and postprandial gastric volumes (GV). AIM: To evaluate the effects of tradipitant relative to placebo on gastric motor functions, satiation, postprandial symptoms, and pharmacokinetics. METHODS: We conducted a randomised, double-blind, placebo-controlled, single-centre study of tradipitant 85 mg or matching placebo b.i.d. for 9 consecutive days in 24 healthy volunteers. During the last 2 days of treatment, participants underwent scintigraphic measurements of GE of 320 kcal egg meal, fasting and postprandial GV by SPECT, and satiation by nutrient drink ingested to maximum tolerated volume (MTV) and symptoms 30 min later. Treatments were compared by Wilcoxon rank sum test. The study had 80% power to detect group differences of 23.6% in GV and 29.2% in GE T1/2 . RESULTS: The two groups of healthy participants were well balanced based on demographic features, age, and BMI. There were nonsignificant positive correlations between blood levels of tradipitant and accommodation GV and GE at 4 h. There were no significant effects of tradipitant, 85 mg b.i.d. for 9 days compared to placebo on GE, GV, satiation, or symptoms 30 min after MTV. CONCLUSION: Tradipitant, 85 mg b.i.d., does not significantly affect gastric motor functions (GV or GE). Importantly, there was no retardation of GE by tradipitant, which is important in relation to its potential use in patients with gastroparesis. CLINIC TRIALS REGISTRY: ClinicalTrials.gov #NCT04849559.

Cannabidiol for Functional Dyspepsia With Normal Gastric Emptying: A Randomized Controlled Trial.

INTRODUCTION: Cannabidiol (CBD), a CBR2 agonist with limited psychic effects, antagonizes CB1/CB2 receptors. Allelic variation CNR1 (gene for CBR1) rs806378 and FAAH rs324420 were associated with altered gut motility and sensation. This study aimed to compare the pharmacodynamics and clinical effects of a 4-week treatment with pharmaceutical-grade CBD vs placebo and assess the interactions of FAAH and CNR1 gene variants on the effects of CBD in patients with functional dyspepsia (FD). METHODS: We performed a randomized, double-blinded, placebo-controlled (1:1 ratio) study of CBD b.i.d. (20 mg/kg/d according to the US Food and Drug Administration escalation guidance) in FD patients with nondelayed gastric emptying (GE) at baseline. Symptoms were assessed by validated daily symptom diary (0-4 scale for upper abdominal pain, nausea, and bloating), weekly assessment of adequate relief, Leuven Postprandial Distress Scale (8 symptoms, adjectival scores rated 0-4 for severity), and quality of life (Short-Form Nepean Dyspepsia Index [average of 10 dimensions each on a 5-point scale]). After the 4-week treatment, all patients underwent measurements of GE of solids, gastric volumes, and Ensure nutrient satiation test. Statistical analysis compared 2 treatments for all endpoints and the effects of CBD in association with FAAH rs324420 and CNR1 rs806378. RESULTS: CBD and placebo effects on physiological functions and patient response outcomes were not significantly different. There were borderline CBD treatment-by-genotype interactions: rs806378 CNR1 with Leuven Postprandial Distress Scale ( P = 0.06) and GE solids ( P = 0.12). DISCUSSION: Approved doses of CBD used off-label do not relieve FD with normal baseline GE of solids or alter gastric motor functions and satiation. CBD treatment-by-gene interactions suggest potential benefits for postprandial distress with CNR1 rs806378 T allele.

Differential mRNA expression in ileal and colonic biopsies in irritable bowel syndrome with diarrhea or constipation.

Altered mucosal functions are documented in jejunal or colorectal mucosa from patients with irritable bowel syndrome (IBS). Our aim was to quantify ileal, ascending, and rectosigmoid colon mucosal expression of genes in IBS-diarrhea (D) and IBS-constipation (C). Forty-four patients with IBS-D, 30 with IBS-C, and 30 healthy volunteers underwent colonoscopic ileal, ascending, and rectosigmoid colon biopsies. Biopsies were stored in RNAlater at -80 °C, purified with on-column DNase, cDNA libraries prepared from 100-200 ng of total RNA, sequenced on Illumina NovaSeq 6000, and analyzed on Illumina's RTA version 3.4.4. Normalized mRNA expression was obtained using MAP-RSeq bioinformatics pipeline. Differential expressions in the groups (Log2-fold change) were measured using the bioinformatics package edgeR 2.6.2, corrected for false discovery rate (PADJ <0.05). There were 30 females with IBS-C and 31 females and 13 males with IBS-D. In IBS-D and IBS-C groups, there were differential expressions of 181 genes in ascending colon and 199 genes in rectosigmoid colon. The majority were gene upregulations in IBS-D with functions reflecting activation of inflammation genes, TRPV1 (visceral hypersensitivity) and neurotransmitters/receptors (specifically purinergic, GABA, and cannabinoid). Although gene differential expressions in the ascending and rectosigmoid colon mucosa of the two groups were different, the diverse upregulated genes involved immune functions, receptors, transmitters, ion channels, and transporters. Conversely, there was reduced expression of PI15 and PI16 genes that inhibit proteases. In patients with IBS-D and IBS-C, differential expressions of genes related to immune, transmitter, nociceptive, protease inhibition, channel, and transporter functions suggest opportunities to reverse the pathobiology and treat patients with IBS.NEW & NOTEWORTHY This study compares gene expression in mucosa of the terminal ileum, right colon, and left colon in patients with diarrhea- or constipation-predominant irritable bowel syndrome (IBS) and contrasts expression between these two disease entities and also between each entity and mucosa from healthy controls. The study shows there is differential expression of genes related to immune, transmitter, nociceptive, ion channel, and transporter functions, as well as reduced serine protease inhibition, in patients with IBS.

Fasting pyloric diameter and distensibility by functional endoluminal imaging probe in unsedated healthy volunteers.

BACKGROUND: Recent studies with functional endoluminal imaging probe (EndoFLIP® ) measure physiologic characteristics of the pylorus. EndoFLIP® has the potential to select optimal candidates for gastric peroral endoscopic myotomy (G-POEM). Normative values of the pylorus using EndoFLIP® have not been established. METHODS: Twenty-four healthy volunteers (20-56 years old; 15 females) underwent unsedated, transoral EndoFLIP® measurements of the pylorus after 8 h of fasting. Measurements of diameter (DM), balloon pressure, and distensibility index (DI) of the pylorus were obtained twice over 5 min at 40, 50, and 60 ml balloon distensions. KEY RESULTS: Pyloric DM at 40, 50, and 60 ml balloon distensions were 13.0 ± 2.5, 14.3 ± 1.8, and 17.2 ± 2.0 mm, respectively. DM with 60 ml distension was notably higher than with 40 and 50 ml distensions. Pyloric DI at 40, 50, and 60 ml distensions were 10.9 ± 4.8, 11.3 ± 5.8, and 11.1 ± 4.3 mm2 /mm Hg, respectively (p = 0.86). Linear regression and Bland-Altman plots showed similar distribution of the DM and DI during the second minute compared with the full 5-min measurements at 50 ml distension, as well as between two sequential measurements using 50 ml distension. With 50 ml balloon distension, intraindividual coefficients of variation (COVintra ) for DM and DI were 13.8% and 29.6%, respectively, and interindividual COV (COVinter ) were 12.6% and 51.3%, respectively. Similar reproducibility was obtained with 40 ml balloon distension. CONCLUSIONS AND INFERENCES: Unsedated EndoFLIP® can be used to characterize human fasting pyloric diameter and distensibility, with best performance observed with 40 ml and 50 ml distensions and data collection during the second minute. Normative values reported serve as reference values for future studies.

Defining normal pouch function in patients with ileal pouch-anal anastomosis: a pilot study.

BACKGROUND: Most patients experience good functional outcomes following ileal pouch-anal anastomosis (IPAA) for ulcerative colitis. AIM: We aimed to determine if asymptomatic patients with an IPAA had findings consistent with normal defecation on standard objective anorectal tests. METHODS: Patients 18-65 years old with IPAA and self-reported healthy pouch function were recruited. Patients with chronic pouchitis, Crohn's disease, anastomotic stricture, or indication for IPAA other than ulcerative or indeterminate colitis were excluded. Patients underwent an interview with an abbreviated Rome Questionnaire followed by high-resolution ano-pouch manometry, balloon expulsion test, pouch barostat, and magnetic resonance (MR) defecography. RESULTS: Twenty patients completed all testing. Six patients were excluded from the final analysis due to symptoms suggestive of pouch evacuation disorder on the abbreviated Rome Questionnaire (n = 2), structural abnormality on MR imaging (n = 3), or both (n = 1). Of the remaining 14 patients, mean anal resting pressure during high-resolution manometry was 72 ± 16 mmHg, mean anal squeeze pressure was 247 ± 69 mmHg, and mean pouch-anal gradient during the simulated evacuation was -27 ± 37 mmHg. The meantime to balloon expulsion was 54 seconds. During dynamic MR defecography, the mean descent of ano-pouch junction was 2.6 cm, and mean pouch evacuation was 44.5% and 74.2% pre- and posttoilet phase, respectively. CONCLUSIONS: A substantial proportion of patients with IPAA and self-reported healthy pouch function have anatomic and/or functional abnormalities of the pouch. In asymptomatic IPAA patients with an anatomically normal pouch, we have proposed normal parameters for high-resolution ano-pouch manometry, time to balloon expulsion, pouch barostat, and MR defecography.

Safety and Efficacy of Eluxadoline in Patients with Irritable Bowel Syndrome-Diarrhea With or Without Bile Acid Diarrhea: Open-Label Study.

BACKGROUND: Eluxadoline, a peripherally acting, mixed µ- and κ-opioid receptor (OR) agonist and δ-OR antagonist, is approved for treatment of adults with irritable bowel syndrome-diarrhea (IBS-D). About a third of IBS-D patients has bile acid diarrhea (BAD); opioids may stimulate TGR5 (bile acid) receptors. AIM: To evaluate eluxadoline's efficacy on altered bowel functions and safety in IBS-D patients with or without BAD. METHODS: In a single-center, phase 4, parallel-group, open-label study, patients with IBS-D (cohort 1) and patients with BAD were treated with eluxadoline, 100 mg tablets BID, with food for 4 weeks. Patients recorded bowel functions by electronic daily diary. BAD was based on fasting serum 7αC4 (> 52.5 ng/mL) or concurrent criteria of increased total or primary fecal BAs excreted in 48 h. We assessed efficacy on treatment compared to baseline in the two cohorts. Primary outcome measures were changes from baseline in average stool consistency Bristol Stool Form Scale (BSFS) score (range 1-7) and safety. RESULTS: Mean changes from baseline in cohorts 1 and 2 (data presented in this order) were similar for: BSFS score averaged over 4 weeks' treatment (- 1.25 and - 1.09); daily bowel movement frequency (- 1.48 and - 0.79); daily urgent bowel movements (- 0.52 and - 0.80); IBS-QoL (5.9 and 13.6); serum 7αC4 (- 5.59 and - 8.78 ng/mL). There were no deaths, serious treatment-emergent adverse events, or discontinuations due to adverse events during the study. CONCLUSION: Eluxadoline is similarly efficacious in the treatment of IBS-D and BAD, and it appears to be safe and efficacious as documented in large clinical trials.

Impact of Bile Acid Diarrhea in Patients With Diarrhea-Predominant Irritable Bowel Syndrome on Symptoms and Quality of Life.

BACKGROUND & AIMS: Bile acid diarrhea (BAD) affects approximately a quarter of patients with irritable bowel syndrome with diarrhea (IBS-D). We aimed to compare the demographics, bowel and somatic symptoms, and quality of life of patients with IBS-D, with or without BAD. METHODS: On one occasion, patients with IBS-D (positive for Rome III criteria) completed the following questionnaires: bowel disease questionnaire, Hospital Anxiety and Depression inventory, general quality of life (Symptom Checklist-90), and IBS-specific quality of life. A fasting serum C4 level higher than 52.5 ng/mL was used as a biomarker for BAD. Statistical analysis included a multiple variable logistic model to identify strong predictors of BAD in IBS-D. RESULTS: Among 219 patients (79% female) with IBS-D, 44 had BAD; the BAD group was significantly older and had a higher body mass index than the patients without BAD. Patients with BAD had more severe bowel dysfunction and impact on IBS-specific quality of life (need of toilet proximity) compared with patients with IBS-D without BAD. Patients with BAD were more likely than other IBS-D groups to receive antidiarrheals, bile acid binders, and antacid secretory agents. The severity of diarrhea and need of toilet proximity were predictors of BAD in IBS-D (P < .01). Patients with BAD were more likely to have a depression score higher than 8 on the Hospital Anxiety and Depression inventory. CONCLUSIONS: There is a greater impact on bowel and somatic symptoms and quality of life in IBS-D with BAD compared with IBS-D without BAD. Screening for BAD in IBS-D is especially relevant, with more severe and frequent diarrhea along with urgency.

Intestinal chemosensitivity in irritable bowel syndrome associates with small intestinal TRPV channel expression.

BACKGROUND: Irritable bowel syndrome (IBS) patients often experience meal-associated symptoms. However, the underlying mechanisms are unclear. AIM: To determine small intestinal mechanisms of lipid-induced symptoms and rectal hypersensitivity in IBS METHODS: We recruited 26 IBS patients (12 IBS-C, 14 IBS-D) and 15 healthy volunteers (HV). In vivo permeability was assessed using saccharide excretion assay. Rectal sensitivity was assessed using a barostat before and after small bowel lipid infusion; symptoms were assessed throughout. Next, an extended upper endoscopy with probe-based confocal laser endomicroscopy (pCLE) was performed with changes induced by lipids. Duodenal and jejunal mucosal biopsies were obtained for transcriptomics. RESULTS: Following lipid infusion, a higher proportion of HV than IBS patients reported no pain, no nausea, no fullness and no urgency (P < 0.05 for all). In a model adjusted for sex and anxiety, IBS-C and IBS-D patients had lower thresholds for first rectal sensation (P = 0.0007) and pain (P = 0.004) than HV. In vivo small intestinal permeability and mean pCLE scores were similar between IBS patients and HV. Post-lipid, pCLE scores were higher than pre-lipid but were not different between groups. Baseline duodenal transient receptor potential vanilloid (TRPV) 1 and 3 expression was increased in IBS-D, and TRPV3 in IBS-C. Duodenal TRPV1 expression correlated with abdominal pain (r = 0.51, FDR = 0.01), and inversely with first rectal sensation (r = -0.48, FDR = 0.01) and pain (r = -0.41, FDR = 0.02) thresholds. CONCLUSION: Lipid infusion elicits a greater symptom response in IBS patients than HV, which is associated with small intestinal expression of TRPV channels. TRPV-mediated small intestinal chemosensitivity may mediate post-meal symptoms in IBS.

Development and Validation of Test for "Leaky Gut" Small Intestinal and Colonic Permeability Using Sugars in Healthy Adults.

BACKGROUND: Oral monosaccharides and disaccharides are used to measure in vivo human gut permeability through urinary excretion. AIMS: The aims were as follows: (1) to obtain normative data on small intestinal and colonic permeability; (2) to assess variance on standard 16 g fiber diet performed twice; (3) to determine whether dietary fiber influences gut permeability measurements; and (4) to present pilot data using 2 selected probes in patients with diarrhea-predominant irritable bowel syndrome (IBS-D). METHODS: Sixty healthy female and male adults, age 18-70 years, participated in 3 randomized studies (2 studies on 16.25 g and 1 study on 32.5 g fiber) in otherwise standardized diets. At each test, the following sugars were ingested: 12C-mannitol, 13C-mannitol, rhamnose (monosaccharides), sucralose, and lactulose (disaccharides). Standardized meals were administered from 24 hours before and during 24 hours post-sugars with 3 urine collections: 0-2, 2-8, and 8-24 hours. Sugars were measured using high-performance liquid chromatography-tandem mass spectrometry. Eighteen patients with IBS-D underwent 24-hour excretion studies after oral 13C-mannitol and lactulose. RESULTS: Baseline sugars (>3-fold above lower limits of quantitation) were identified in the 3 studies: 12C-mannitol in all participants; sucralose in 4-8, and rhamnose in 1-3. Median excretions/24 h (percentage of administered dose) for 13C-mannitol, rhamnose, lactulose, and sucralose were ∼30%, ∼15%, 0.32%, and 2.3%, respectively. 13C-mannitol and rhamnose reflected mainly small intestinal permeability. Intraindividual saccharide excretions were consistent, with minor differences with 16.25 g vs 32.5 g fiber diets. Median interindividual coefficient of variation was 76.5% (10-90 percentile: 34.6-111.0). There were no significant effects of sex, age, or body mass index on permeability measurements in health. 13C-mannitol measurements are feasible in IBS-D. CONCLUSIONS: Baseline 12C-mannitol excretion precludes its use; 13C-mannitol is the preferred probe for small intestinal permeability.

Expanding criteria for slow colonic transit in patients being evaluated for chronic constipation by scintigraphy.

BACKGROUND: Colonic transit measurement [geometric center (GC) at 24 and 48 hours] identifies slow transit constipation (STC) in patients with chronic constipation. AIM: To evaluate the utility of the difference between GC24 and GC48 (Δ48-24 ) to identify STC in adults with chronic constipation. METHODS: We reviewed medical records of 250 patients, aged 18-75 years, who underwent colonic transit by scintigraphy during 1994-2019 for investigation of chronic constipation. Data collected included demographics, medical and surgical histories, and anorectal manometry. We used colonic transit from 220 healthy controls to identify the 5th percentile for diagnosing STC: 1.3 at 24 hours, and 1.9 at 48 hours. In addition, the 5th percentile for Δ48-24 was 0.38 for females and 0.29 for males. Data are reported as median and IQR [Q1, Q3]). KEY RESULTS: Among the 250 patients [median age 42.5 years (IQR 30.75, 56), 84% female], based on GC24 < 1.3, 52 (20.8%) had STC (3 males, 49 females); and based on GC48 < 1.9, 28(11.2%) had STC (3 males, 25 females). Colonic transit was normal in 74.8%. In the groups with normal GC24 and GC48, Δ48-24 identified an additional 32(15.1%) of 212 female patients and 4 (10.5%) of 38 male patients with slow progression of colonic transit between 24 and 48 hours. Among these 36 patients with abnormal Δ48-24 , 13(36.1%) had evidence of rectal evacuation disorder. CONCLUSIONS & INFERENCES: Δ48-24 measurement on scintigraphic colonic transit can identify an additional 9.2% of STC in patients with constipation without rectal evacuation disorder and can help individualize treatment of chronic constipation.