Serum triamcinolone levels during intensive, inpatient wet-dressing therapy.

BACKGROUND: Wet dressings combined with topical corticosteroids are beneficial for patients with generalized and refractory dermatosis; however, to our knowledge, serum levels after topical corticosteroid absorption during intensive therapy have not been reported previously. AIM: To examine serum levels of triamcinolone acetonide (TAC) after topical corticosteroid application during intensive wet-dressing therapy. METHODS: We performed a retrospective study of adult patients admitted for inpatient wet-dressing therapy from 7 November 2015 to 24 June 2016. Data were collected on sex, age, body surface area, TAC serum levels, number of wet-dressing changes after 24 and 48 h, and type of wet dressing. RESULTS: In total, 29 patients (14 men, 15 women) were assessed. Median [interquartile range (IQR)] age was 57 years (51.5-67.0 years) and involved body surface area was 1.98 m2 (1.88-2.15) m2 . Before the 24-hour blood draw, patients had received 1-3 dressing changes. Median (IQR) TAC level at 24 h was 0.33 µg/dL (0.20-0.58 µg/dL), with no significant difference noted between the number of dressing changes and TAC serum level. At 48 h, results of a serum TAC test were available for 22 patients with 2-6 dressing changes. Mean (IQR) serum level was 0.30 µg/dL (0.30-0.87 µg/dL). For each additional dressing change, there was an estimated 0.21 µg/dL increase in TAC serum level (95% CI 0.11-0.31; P < 0.001). TAC serum level was not significantly associated with sex, age, body surface area or dressing type. CONCLUSIONS: Intensive, inpatient wet-dressing therapy is associated with detectable TAC serum levels. However, we suspect that topical TAC has a primarily local therapeutic effect on the skin.

Reproducibility of gastric emptying assessed with scintigraphy in patients with upper GI symptoms.

BACKGROUND: The reproducibility of gastric emptying (GE) measured with scintigraphy in patients is poorly understood. Our aims were to assess the intra and inter-individual reproducibility of these parameters in patients with upper gastrointestinal symptoms. METHODS: Sixty patients (21 diabetics, 39 non-diabetics) with upper gastrointestinal symptoms underwent scintigraphic-assessment of GE of a solid meal (296 kcal, 30% fat) over 4 hours on two occasions at an average interval of 15 days. The concordance correlation coefficient (CCC), intra and inter-individual coefficients of variation (COV) of GE endpoints were analyzed. RESULTS: The GE t1/2 was 134 ± 8 minutes (mean ± SEM) for the first and 128 ± 6 minutes for the second study. The mean (95% CI) CCC between the two studies was 0.79 (0.67, 0.87) for GE at 1 hour, 0.83 (0.75, 0.9) for GE at 2 hours, 0.54 (0.34, 0.7) for GE at 4 hours, and 0.79 (0.68, 0.86) for GE t1/2 . However, in 18 of 60 patients (30%), the characterization of GE as normal, delayed, or rapid differed between the first and second studies. For gastric empting t1/2 , the inter-individual coefficients of variation was 40%; the intra-individual COV was 20%, comparable in diabetics and non-diabetics, and greater in patients with rapid (28%) than delayed (18%) or normal GE (12%). CONCLUSIONS & INFERENCES: Among patients with upper gastrointestinal symptoms, GE measured with scintigraphy is relatively reproducible. In 30% of cases, the interpretation was different between the two assessments. Hence, a diagnosis of gastroparesis based on a single study may occasionally be inaccurate.

Cannabinoids and gastrointestinal motility: Pharmacology, clinical effects, and potential therapeutics in humans.

BACKGROUND: Cannabinoid agents and cannabis are frequently used for relief of diverse gastrointestinal symptoms. PURPOSE: The objective of this article is to increase the awareness of gastroenterologists to the effects of cannabinoids on gastrointestinal motility, as gastroenterologists are likely to encounter patients who are taking cannabinoids, or those with dysmotility that may be associated with cannabinoid mechanisms. The non-selective cannabinoid agonist, dronabinol, retards gastric emptying and inhibits colonic tone and phasic pressure activity. In addition to the well-recognized manifestations of cannabinoid hyperemesis, cannabinoid mechanisms result in human and animal models of gastrointestinal and colonic dysmotility. Decreased enteric FAAH activity is associated with colonic inertia in slow transit constipation and, conversely, the orphan G protein-coupled receptor, GPR55, is overexpressed in streptozotocin-induced gastroparesis, suggesting it is involved in inhibition of antral motility. Experimental therapies in gastrointestinal motility and functional disorders are focused predominantly on pain relief mediated through cannabinoid 2 receptors or inhibition of DAGLα to normalize colonic transit. In summary, cannabinoid mechanisms and pharmacology are relevant to the current and future practice of clinical gastroenterology.

Comparison of pH and motility of the small intestine of healthy subjects and patients with symptomatic constipation using the wireless motility capsule.

Gastrointestinal luminal pH shows a rise from the duodenum to the terminal ileum in healthy individuals. Our objectives were to compare the pH in the proximal small intestine (SI) (first 60 min of small intestinal transit) lumen of human volunteers and patients with symptomatic constipation; to quantify contractile pressure profiles of the proximal SI, and to assess the relationship between luminally-recorded contractile pressure and small intestinal transit times (SITT) of a non-disintegrating capsule that measures pH and pressure activity (wireless motility capsule). We used previously acquired records from 39 healthy subjects and 41 patients with symptomatic constipation. Mean pH (±SD) of the proximal SI was similar in healthy subjects and patients with constipation at 6.2 (±0.6) and 6.3 (±0.4), respectively. In 13 of the healthy subjects, pH did not rise uniformly in the proximal SI though the pHmedian was 6.0 (5th, 95th percentiles 3.09, 7.06) and the pH fluctuated over a mean period of 28 min. Large inter-individual variability in frequency of pressure activity (Ct) and area under pressure curve (AUC) were observed in the proximal SI of healthy subjects and patients with constipation. Median AUC was 3996 mmHg s-1 (5th, 95th percentiles 948, 16866 mmHg s-1) in these two populations combined. Ct and AUC showed a strong direct linear correlation at r = 0.91, p < 1 × 10-6. An inverse correlation (suggesting longer SITT with lower pressure activity) was observed between Ct/AUC and SITT in both healthy subjects and patients with symptomatic constipation. The pooled results for both groups showed: AUC and SITT correlation at r = -0.49, p < 1 × 10-6. We concluded that both the frequency and amplitude of contractions in the proximal SI are important for the propagation of non-disintegrating capsules. The observed pH fluctuations in the proximal SI may impact supersaturation and precipitation of weakly basic drugs.

Allelic variant in the glucagon-like peptide 1 receptor gene associated with greater effect of liraglutide and exenatide on gastric emptying: A pilot pharmacogenetics study.

BACKGROUND: Weight loss in response to the long-acting GLP-1 receptor (GLP1R) analog, liraglutide, is correlated with delay in gastric-emptying (GE). The aim of this pilot study was to assess whether specific genetic variants in GLP1R or TCF7L2 are associated with delayed GE and weight loss in obese patients treated with liraglutide or the short-acting GLP-1 agonist, exenatide. METHODS: We evaluated in obese individuals the associations of genetic variations of GLP1R (rs6923761) and TCF7L2 (rs7903146) on GE T1/2 and weight from two trials that evaluated separately exenatide, 5 µg BID for 30 days, or liraglutide, 3 mg daily for 5 weeks. Data were analyzed using the dominant genetic model and intention-to-treat analysis. KEY RESULTS: There was a significant correlation between changes in weight and GE T1/2 (rs  = -.382, P = .004). GLP1R rs6923761 minor allele A (AA_AG) carriers who received either exenatide or liraglutide had greater delay in GE T1/2 relative to baseline (117.9 ± 27.5 [SEM] minutes and 128.9 ± 38.32 minutes) compared to GG genotype (95.8 ± 30.4 minutes and 61.4 ± 21.4 minutes, respectively; P = .11). There was a non-significant difference in weight loss based on GLP1R rs6923761 genotype after 5 weeks of treatment. There were no significant correlations with TCF7L2 (rs7903146) genotype. CONCLUSIONS & INFERENCES: The minor A allele of GLP1R (rs6923761) is associated with greater delay in GE T1/2 in response to liraglutide and exenatide. These studies provide data to plan pharmacogenetics testing of the hypothesis that GLP1R (rs6923761) influences weight loss in response to GLP1R agonists.

Effects of naloxegol on whole gut transit in opioid-naïve healthy subjects receiving codeine: A randomized, controlled trial.

BACKGROUND: Nausea, vomiting, and constipation (OIC) are common adverse effects of acute or chronic opioid use. Naloxegol (25 mg) is an approved peripherally active mu-opiate opioid receptor antagonist. AIM: To compare the effects on pan-gut transit of treatment with codeine, naloxegol, or combination in healthy volunteers. METHODS: We conducted a randomized, double-blind, placebo-controlled, single-center, parallel-group study in 72 healthy opioid-naïve adults, randomized to: codeine (30 mg q.i.d.), naloxegol (25 mg daily), codeine and naloxegol, or matching placebo. During 3 days of treatment, we measured gastric emptying (GE) T1/2 , colonic filling at 6 hours (CF6), colonic geometric center at 24 and 48 hours, and ascending colon emptying (ACE) T1/2 . KEY RESULTS: Participants were 59.7% women, median BMI 25.0 kg/m2 , and median age 33.8 years. Codeine significantly retarded GE T1/2, CF6, overall colonic transit, and ACE T1/2 . There was significant difference (P = .026) in GE T1/2 between codeine (144.0 min [IQR 110.5-238.6]) and naloxegol (95.5 min [89.1-135.4]). There was a significant overall group difference in CF6 (P = .023), with significant difference (P = .019) between codeine (11.0% [0.0-45.0]) and naloxegol (51% [18.8-76.2]). However, no significant differences were found between codeine-treated participants concomitantly receiving placebo or naloxegol. CONCLUSIONS AND INFERENCES: Short-term administration of naloxegol (25 mg) in healthy, opioid-naïve volunteers does not reverse the retardation of gastric, small bowel, or colonic transit induced by acute administration of codeine. Further studies with naloxegol at higher dose are warranted to assess the ability to reverse the retardation of transit caused by acute administration of codeine in opioid-naïve subjects.

Cardiovascular safety of prokinetic agents: A focus on drug-induced arrhythmias.

BACKGROUND: Gastrointestinal sensorimotor dysfunction underlies a wide range of esophageal, gastric, and intestinal motility and functional disorders that collectively constitute nearly half of all referrals to gastroenterologists. As a result, substantial effort has been dedicated toward the development of prokinetic agents intended to augment or restore normal gastrointestinal motility. However, the use of several clinically efficacious gastroprokinetic agents, such as cisapride, domperidone, erythromycin, and tegaserod, is associated with unfavorable cardiovascular safety profiles, leading to restrictions in their use. PURPOSE: The purpose of this review is to detail the cellular and molecular mechanisms that lead commonly to drug-induced cardiac arrhythmias, specifically drug-induced long QT syndrome, torsades de pointes, and ventricular fibrillation, to examine the cardiovascular safety profiles of several classes of prokinetic agents currently in clinical use, and to explore potential strategies by which the risk of drug-induced cardiac arrhythmia associated with prokinetic agents and other QT interval prolonging medications can be mitigated successfully.

Effects of Antidepressants on Gastric Function in Patients with Functional Dyspepsia.

BACKGROUND: Functional dyspepsia (FD) is a highly prevalent functional bowel disorder. The effects of antidepressant therapy (ADTx) on gastric sensorimotor function in FD patients are poorly understood. AIMS: Determine whether FD and subtypes with abnormalities in gastric function respond differently to ADTx compared to those with normal physiology. METHODS: This multicenter, prospective trial randomized FD patients to 12 weeks of amitriptyline (AMI; 50 mg), escitalopram (ESC; 10 mg), or matching placebo. Demographics, symptoms, psychological distress, gastric emptying, and satiation were measured. Gastric accommodation (GA) using single-photon emission computed tomography imaging was performed in a subset of patients. An intent to treat analysis included all randomized subjects. The effect of treatment on gastric emptying was assessed using ANCOVA. A post hoc appraisal of the data was performed categorizing patients according to the Rome III subgrouping (PDS and EPS). RESULTS: In total, 292 subjects were randomized; mean age=44 yrs. 21% had delayed gastric emptying. Neither antidepressant altered gastric emptying, even in those with baseline delayed gastric emptying. GA increased with ADTx (P=0.02). Neither antidepressant affected the maximal-tolerated volume (MTV) of the nutrient drink test although aggregate symptom scores improved compared to placebo (P=0.04). Patients with the combined EPS-PDS subtype (48%) had a lower MTV on the nutrient drink test compared to the EPS group at baseline (P=0.02). Postprandial bloating improved with both AMI (P=0.03) and ESC (P=0.02). CONCLUSIONS: Amitriptyline (50 mg) improves FD symptoms but does not delay gastric emptying, even in patients with baseline delayed gastric emptying. GA improved with low-dose ADTx; the precise mechanism of action is unknown warranting further study.

Insights on efficacious doses of PAMORAs for patients on chronic opioid therapy or opioid-naïve patients.

BACKGROUND: Opioid-induced constipation (OIC) is a major side effect of opioid use. Centrally acting antagonists result in opioid withdrawal or worsening of pain and lead to use of peripherally acting mu-opioid receptor antagonists (PAMORAs). The required doses of the PAMORAs, methylnaltrexone and naloxegol, in the treatment of OIC are well established in chronic opioid users. OIC may occur after short duration of opioid treatment; the required doses of naloxone, naltrexone, and PAMORAs in opioid-naïve subjects (with no opioid use for at least 3 months) are unclear. The aim of this review was to evaluate the PAMORA dose required for opioid-naïve subjects to achieve similar beneficial effects on symptoms or valid surrogates to those observed in chronic opioid users. METHODS: A PubMed search of µ-opioid antagonists to counter µ-opioid effects included terms: naloxone, naltrexone, methylnaltrexone, alvimopan, and naloxegol, as well as OIC and colonic transit. KEY RESULTS: The approved dose of methylnaltrexone in chronic opioid users, 0.3 mg/kg subcutaneous (SQ), did not affect motility in opioid-naïve subjects. Trials investigating the required dose of alvimopan showed 0.5-1 mg dose was efficacious in treating OIC; a 10-fold higher dose (12 mg) of alvimopan is needed to block effects of codeine on small bowel and colonic transit in opioid-naïve subjects compared to chronic opioid users. Opioid-naïve users need 125 mg of naloxegol to reverse the effects of opioids on transit; this is in contrast to the 12.5 to 25 mg needed to treat OIC in chronic opioid users. CONCLUSIONS & INFERENCES: Opioid-naïve subjects require a higher dose of PAMORA than chronic opioid users to achieve µ-opioid antagonist effect.

Performance characteristics of serum C4 and FGF19 measurements to exclude the diagnosis of bile acid diarrhoea in IBS-diarrhoea and functional diarrhoea.

BACKGROUND: The serum biomarkers, elevated 7αC4 (C4) and decreased FGF19, have been proposed as screening tests for bile acid diarrhoea. AIM: To analyse prevalence, specificity and reproducibility of fasting C4 and FGF19 in identifying bile acid diarrhoea in patients with irritable bowel syndrome with predominant diarrhoea or functional diarrhoea (summarised as IBS-D). METHODS: We prospectively studied fasting serum C4 and FGF19 in 101 IBS-D patients; we reviewed data from 37 of the 101 patients with prior fasting serum C4 and FGF19 and from 30 of the 101 patients with prior faecal bile acids per 48 hours. We compared results with normal values (C4 ≥52.5 ng/mL [n=184], FGF-19 ≤61.7 pg/mL [n=50]). We used Spearman correlation and Bland-Altman plots to appraise reproducibility. RESULTS: Among the 101 patients, there was a negative correlation between serum C4 and FGF19 (Rs=-.342, P=.0005). Bile acid diarrhoea was diagnosed in 10 patients based on elevated serum C4 levels (mean 23.5±23.1 [SD] ng/mL) and 21 patients based on decreased FGF19 levels (121.6±84.2 pg/mL). With replicate tests in patients with stable IBS-D, 78% of C4 and 70% of FGF19 measurements remained concordant, with 3% and 11% respectively consistently positive for bile acid diarrhoea in the 101 patients. Compared to 48 hours faecal bile acids, specificity for C4 and FGF19 was 83% and 78%, respectively. Bland-Altman plots demonstrated greater reliability of C4 than FGF19. CONCLUSIONS: Among 101 patents with IBS-D, fasting FGF19 and C4 levels had good specificity and negative predictive value, suggesting utility as screening tests to exclude bile acid diarrhoea.

Secretory diarrhea and hypokalemia associated with colonic pseudo-obstruction: A case study and systematic analysis of the literature.

BACKGROUND: Colonic pseudo-obstruction (CPO) is characterized by colonic distention in the absence of mechanical obstruction or toxic megacolon. Concomitant secretory diarrhea (SD) with hypokalemia (SD-CPO) due to gastrointestinal (GI) loss requires further characterization. AIM: To perform a systematic review of SD-CPO, report a case study, and compare SD-CPO with classical CPO (C-CPO). METHODS: We performed a search of MEDLINE, EMBASE, Cochrane, and Scopus for reports based on a priori criteria for CPO, SD and GI loss of potassium. An additional case at Mayo Clinic was included. RESULTS: Nine publications met inclusion criteria, with a total of 14 cases. Six studies had high, three moderate, and our case high methodological quality. Median age was 74 years (66-97), with 2:1 male/female ratio. Kidney disease was present in 6/14 patients. Diarrhea was described as profuse, watery, or viscous in 10 patients. Median serum, stool, and urine potassium concentrations (mmol/L) were 2.4 (range: 1.9-3.1), 137 (100-180), and 17 (8-40), respectively. Maximal diameter of colon and cecum (median) were 10.2 cm and 10.5 cm, respectively. Conservative therapy alone was effective in five out of 14 patients. Median potassium supplementation was 124 mEq/d (40-300). Colonic decompression was effective in three out of six patients; one had a total colectomy; three out of 14 had died. The main differences between SD-CPO and C-CPO were lower responses to treatments: conservative measures (35.7% vs 73.6%, P=.01), neostigmine (17% vs 89.2%, P<.001), and colonic decompression (50% vs 82.4%, P=.02). CONCLUSION: SD-CPO is a rare phenotype associated with increased fecal potassium and is more difficult to treat than C-CPO.

Upper gastrointestinal complications following ablation therapy for atrial fibrillation.

BACKGROUND: Following ablation therapy for cardiac arrhythmias, patients may develop upper gastrointestinal (UGI) symptoms. The vagus nerve is close to the atria and may be affected by ablating energy. AIM: To identify structural or functional complications in UGI tract following ablation for atrial fibrillation (AF) and clinical outcomes and association with vagal dysfunction. METHODS: Using natural language processing of electronic medical records and an AF ablation database of 5380 patients treated during 17 years, we identified 40 patients with UGI complications. We evaluated vagal dysfunction by electrocardiogram (ECG) showing lack of sinus arrhythmia (variation in R-R interval by ≥120 milliseconds, in presence of normal sinus P waves and constant P-R interval). KEY RESULTS: Among 40 patients: (A) eight had structural GI complications confirmed by diagnostic tests: seven with esophageal ulcer/erosions and no signs of UGI bleeding and one developed esophagopericardial fistula (and survived with treatment); (B) 15 had functional UGI complications confirmed by objective motility tests. Nine had newly developed symptoms and six had aggravated symptoms; and (C) the remaining 17 had GI symptoms without relevant diagnostic results. Most UGI issues resolved spontaneously or with conservative treatment. However, 2 died several weeks after ablation procedure; cause of death was suspected atrioesophageal fistula or esophageal rupture. Vagal dysfunction persisted for 3 months in 13 and was transient in 8. CONCLUSIONS/INFERENCES: Although most GI issues resolved spontaneously, there should be a high index of clinical suspicion in patients with persistent symptoms. Vagal dysfunction may serve as a marker of more extensive tissue damage.

Rectal gas volume: Defining cut-offs for screening for evacuation disorders in patients with constipation.

BACKGROUND: Diagnosis of rectal evacuation disorders (RED) is currently based on anorectal manometry (ARM) and evacuation tests in specialized laboratories; we recently showed higher rectal gas volume (RGV) and maximum rectal gas transaxial area (MRGTA) measured on abdominal and pelvic computed tomography (CT) in patients with documented RED.The aim of this study was to obtain cut-off values of RGV, MRGTA, and rectal area on scout film (RASF) to differentiate constipated patients with RED from those without RED, based on ARM, balloon expulsion test (BET), and colon transit test. METHODS: We identified 118 constipated patients (65 with RED) with prior record of CT. Using standard CT software, we used a variable region of interest (ROI) program to measure RGV, MRTGA, and RASF, as previously described. We constructed receiver operating characteristics curves based on different values, and we estimated AUC, specificity, and positive predictive value (PPV) to detect RED in patients with constipation. KEY RESULTS: Receiver operating characteristics of the models to predict RED showed AUC 0.751 for RGV and 0.737 for MRGTA (both P<.001), and 0.623 for RASF (P=.029). At specificity of 90%, RGV of 30 mL had a PPV 77.3%, MRGTA of 10 cm2 had a PPV 75.0%, and RFAS of 9 cm2 had a PPV of 68.8% for identifying constipated patients with RED. CONCLUSIONS & INFERENCES: Rectal gas measurements on abdominal imaging may indicate RED in patients with constipation. At ~90% specificity for RED, RGV of 20 or 30 mL or MRGTA of 10 cm2 on CT has PPV ~75%, and RASF of >9 cm2 has PPV of ~69%.

A single-center, prospective, double-blind, sham-controlled, randomized study of the effect of a vibrating capsule on colonic transit in patients with chronic constipation.

BACKGROUND: In an open-label study of 26 patients with IBS-C and chronic constipation, treatment with a vibrating (VIBRANT) capsule twice a week for 7.5 weeks resulted in 88.5% responders. Effects on colonic transit are unclear. We aimed to compare effects of VIBRANT and sham capsule treatment on colonic transit in patients with functional constipation. METHODS: Patients with functional constipation (Rome III criteria) were randomized to VIBRANT or sham capsule treatment for 8 weeks and underwent scintigraphic colonic transit measurements during week 8. We estimated the overall rate of colonic transit from the slope of progression of colonic geometric center over 48 hours. The capsule was activated 8 hours after ingestion, and the vibration sequence included 240 cycles. KEY RESULTS: There were no significant group differences in overall colonic transit [GC48, 2.76 (IQR 2.42-4.03) for sham group and 3.46 (2.55-4.61) for active treatment group (P=.13)]. Additionally, the progression of the isotope through the colon was numerically faster, though not significantly different (slope, P=.14) in the VIBRANT capsule group compared to the sham group. Three participants in the VIBRANT capsule group had accelerated colonic transit at 32 hours and faster colonic transit slope compared to the 95th percentile of the sham group. CONCLUSIONS AND INFERENCES: Although there were no group differences between VIBRANT and sham capsule treatment on colonic transit, at least one (and possibly three) of 12 patients receiving the VIBRANT capsule had faster colonic transit. The vibration parameters to accelerate colonic transit in patients with functional constipation require further optimization.

Opioid analgesic use among patients presenting with acute abdominal pain and factors associated with surgical diagnoses.

BACKGROUND: The prevalence of chronic opioid use among non-cancer patients presenting with acute abdominal pain (AAP) is unknown. The aim was to characterize opioid use, constipation, diagnoses, and risk factors for surgical diagnoses among non-cancer patients presenting with AAP to an emergency department (ED). METHODS: We performed a retrospective, observational cohort study of all (n=16,121) adult patients (88% from MN, IA and WI) presenting during 2014 with AAP. We used electronic medical records, and focused on 2352 adults with AAP who underwent abdominal CT scan within 24 hours of presentation. We determined odds ratios of association with constipation and features predicting conditions that may require surgery (surgical diagnosis). KEY RESULTS: There were 2352 eligible patients; 18.8% were opioid users. Constipation was more frequent in opioid (35.1%) compared to non-opioid users [OR 2.88 (95% CI 2.28, 3.62)]. Prevalence of surgical diagnosis in the opioid and non-opioid users was 35.3% and 41.7% respectively (P=.019). By univariate analysis, age and neutrophil count independently predicted increased risk, and chronic opioid use decreased risk of surgical diagnosis. Internal validation of logistic models using a randomly selected validation subset (25% of entire cohort, 587/2352) showed receiver operating characteristic (ROC) curves for the validation and full cohorts were similar. CONCLUSIONS AND INFERENCES: Approximately 19% of adults presenting with AAP were opioid users; constipation is almost three times as likely in opioid users compared to non-opioid users presenting with AAP. Factors significantly associated with altered risk of surgical diagnoses were age, opioid use, and neutrophil count.

Exploring hypotheses and rationale for causes of infantile colic.

BACKGROUND: Infantile colic is a frequent problem in neonates and infants. This review addresses current management including the results for nutrient modifications; soy-based formulas; and prebiotics, probiotics, and synbiotics. PURPOSE: Given the evidence that there is still an unmet clinical need, as current treatments are incompletely efficacious, we have examined the evidence around three hypothetical mechanisms that could potentially be involved in etiopathogenesis of infantile colic: immaturity of bile acid mechanisms that alter intraluminal and absorptive mechanisms, immaturity in motility and alterations in the microbiome. Understanding these potential mechanisms may lead to the introduction of diagnostic procedures that should enhance the selection or individualization of therapy for infantile colic.

Presence of intraepithelial food antigen in patients with active eosinophilic oesophagitis.

BACKGROUND: Although eosinophilic oesophagitis (EoE) is putatively mediated by an abnormal response to food antigen, the oesophagus is considered relatively impermeable to large molecules. AIM: To assess whether food antigens penetrate the oesophageal mucosa in patients with EoE. METHODS: Anti-gliadin staining was performed in three groups: active EoE, inactive EoE and EoE patients on a low or gluten free diet. To appraise the specificity of our results, we also performed gliadin staining on six patients without oesophageal disease who were consuming gluten. The groups with EoE on gluten also underwent endoscopic infusion with gluten containing soy sauce and repeat biopsies during the endoscopy. We measured eosinophil density, dilated intercellular spaces (on a 0-4+ scale) and gliadin in oesophageal mucosa by immunofluorescence. RESULTS: Patients with active EoE had significantly greater epithelial density of anti-gliadin staining when compared to inactive EoE (P < 0.0065) and gluten-free patients (P < 0.0008) at baseline and after soy infusion. Gliadin was not detected in non-EoE control patients. The distribution of gliadin was both cytoplasmic and nuclear. There was good correlation of dilated intercellular spaces grade and total gliadin staining intensity (r = 0.577, P = 0.0077). Acute oesophageal perfusion of a commercial gliadin-rich soy sauce did not lead to an increase in gliadin staining in active or inactive EoE. CONCLUSION: These findings suggest, although do not prove, that antigen penetration in active eosinophilic oesophagitis might be facilitated by impairment of epithelial integrity.

Effects of ghrelin receptor agonist, relamorelin, on gastric motor functions and satiation in healthy volunteers.

BACKGROUND: Synthetic human ghrelin accelerates gastric emptying, reduces gastric accommodation, and results in numerical increases in postprandial symptom scores. The ghrelin receptor agonist, relamorelin, accelerates gastric emptying in patients with diabetic gastroparesis. AIM: To measure pharmacological effects of relamorelin on gastric accommodation, distal antral motility, and satiation in healthy volunteers. METHODS: In a placebo-controlled, double-blind, randomized study of 16 healthy volunteers, we compared effects of 30 µg subcutaneous (s.c.) relamorelin to placebo on: (i) gastric volumes measured by single photon emission computed tomography, (ii) 1-h postprandial distal antral motility index (MI) by 15-lumen perfusion gastroduodenal manometry, and (iii) satiation tested by Ensure nutrient drink test. Primary endpoints were: fasting and postprandial gastric volumes, distal antral phasic pressure activity (number of contractions, mean amplitude, and MI), and maximum tolerated volume. Results were normally distributed and the two treatment groups were compared using t-test. KEY RESULTS: Relamorelin, 30 µg s.c., significantly increased the number of contractions in the distal antrum during 0-60 min postmeal when compared to placebo (p = 0.022); this was also observed in the first two 15-min periods (p = 0.005 and 0.015 for number of contractions 0-15 and 16-30). There was borderline increase in MI0-15 (p = 0.055) and numerically increased MI0-60 (p = 0.139) and MI16-30 (p = 0.116). The amplitude of contractions was not significantly increased. Relamorelin did not significantly alter fasting or postprandial gastric volumes, gastric accommodation, or satiation volumes and symptoms. CONCLUSIONS & INFERENCES: Relamorelin increases frequency of distal antral motility contractions without significant effects on amplitude of contractions. The lack of inhibition of accommodation and absence of increase in satiation symptoms support relamorelin for the treatment of symptomatic gastroparesis (ClinicalTrials.gov NCT02466711).