Safety and Efficacy of Oral Azithromycin for Gastrointestinal Dysmotility in Pediatric Patients.

Gastrointestinal (GI) dysmotility impedes nutrient delivery in critically ill patients with major burns. We aimed to quantify the incidence, timing, and factors associated with GI dysmotility and subsequent nutrition delivery. A 10-year retrospective observational study included mechanically ventilated, adult, critically ill patients with ≥15% total body surface area (TBSA) burns receiving nutrition support. Patients with a single gastric residual volume ≥250 mL were categorized as having GI dysmotility. Daily medical and nutrition data were extracted for ≤14 days in the intensive care unit (ICU). Data are mean (SD) or median (interquartile range). Factors associated with GI dysmotility and the effect on nutrition and clinical outcomes were assessed. Fifty-nine patients were eligible; 51% (n = 30) with GI dysmotility and 49% (n = 29) without. Baseline characteristics (dysmotility vs no dysmotility) were age (48 [33-60] vs 34 [26-46] years); Acute Physiology and Chronic Health Evaluation II score (16 [12-17] vs 13 [10-16]); sex ([men] 80% vs 86%); and TBSA (49% [35%-59%] vs 38% [26%-55%]). Older age was associated with increased probability of dysmotility (P = .049). GI dysmotility occurred 32 (19-63) hours after ICU admission but was not associated with reduced nutrient delivery. Postpyloric tube insertions were attempted in 83% (n = 25) of patients, with 72% (n = 18) being successful. Postpyloric feeding achieved higher nutrition adequacy than gastric feeding (energy: 82% [95% CI, 70-94] vs 68% [95% CI, 63-74], P = .036; protein: 75% [95% CI, 65-86] vs 61% [95% CI, 56-65], P = .009). GI dysmotility occurs early in critically ill burn patients, and postpyloric feeding improves nutrition delivery.

microRNAs (miRNAs) are key regulators of both physiological and pathophysiological mechanisms in diabetes and gastrointestinal (GI) dysmotility. Our previous studies have demonstrated the therapeutic potential of miR-10a-5p mimic and miR-10b-5p mimic (miR-10a/b mimics) in rescuing diabetes and GI dysmotility in murine models of diabetes. In this study, we elucidated the safety profile of a long-term treatment with miR-10a/b mimics in diabetic mice. Male C57BL/6 mice were fed a high-fat, high-sucrose diet (HFHSD) to induce diabetes and treated by five subcutaneous injections of miR-10a/b mimics for a 5 month period. We examined the long-term effects of the miRNA mimics on diabetes and GI dysmotility, including an assessment of potential risks for cancer and inflammation in the liver and colon using biomarkers. HFHSD-induced diabetic mice subcutaneously injected with miR-10a/b mimics on a monthly basis for 5 consecutive months exhibited a marked reduction in fasting blood glucose levels with restoration of insulin and significant weight loss, improved glucose and insulin intolerance, and restored GI transit time. In addition, the miR-10a/b mimic-treated diabetic mice showed no indication of risk for cancer development or inflammation induction in the liver, colon, and blood for 5 months post-injections. This longitudinal study demonstrates that miR-10a/b mimics, when subcutaneously administered in diabetic mice, effectively alleviate diabetes and GI dysmotility for 5 months with no discernible risk for cancer or inflammation in the liver and colon. The sustained efficacy and favorable safety profiles position miR-10a/b mimics as promising candidates in miRNA-based therapeutics for diabetes and GI dysmotility.

Introduction: Wireless Motility Capsule (WMC) is used for the assessment of diabetic (DM) patients with suspected gastrointestinal (GI) dysmotility. However, the impact of WMC findings on the clinical management and subsequent symptomatic improvement is not clearly understood. Our aim was to assess the change in therapy and resulting change in symptoms based on WMC testing in DM patients with suspected GI dysmotility. Methods: Retrospective chart review of all DM patients who had WMC testing at our institution from 2010 to 2015 was performed. Only patients for whom follow-up information was available regarding medication changes and response to treatment were included. Patients with a previous history of gut surgery, inflammatory bowel disease or gut cancer were excluded. Results of WMC testing were classified as isolated vs. multiregional dysmotility. The presenting symptoms, change in treatment after WMC testing and symptom response were noted. Chi-square test for independence was used to compare the extent of involvement on WMC testing in those who responded to therapy. Results: A total of 47 patients were included. Mean age was 46 ± 14 years with 77% being females. The prevalence of presenting symptoms is illustrated in figure 1. Nausea and/or vomiting was the most commonly reported symptom (96%), followed by abdominal pain (74%), constipation (72%), bloating (53%) and diarrhea (32%). Treatment prescribed included: Ondansetron/Promethazine (N=27), Erythromycin (N=20), Metoclopramide (N=26), Domperidone (N=14), Linaclotide (N=14), Polyethylene glycol (N=13), Lubiprostone (N=7) and Mirtazapine (N=4). WMC testing was abnormal in 37 (79%) patients. Among those, treatment changes as a result of WMC testing were made in 25 patients (66%). Overall, 27 (57%) patients reported improvement in at least one symptom (Figure 2). In those patients, the extent of involvement on WMC testing was not significantly different, with 52% having an isolated dysmotility and 48% having multiregional involvement (p=0.9) Response to treatment was highest for Linaclotide (64%) and lowest for Metoclopramide (19%). Response to the rest of the medications is presented in figure 3.Figure 1Figure 2Figure 3Conclusion: WMC testing leads to changes in management in 66% of DM patients with symptoms of GI dysmotility. Symptom improvement was noted in 57% of patients. Isolated vs multiregional pattern of underlying GI dysmotility does not seem to impact symptom improvement. Multiple treatment options are available with varying symptom response.

Introduction: There is an unmet clinical need to identify biomarkers predicting which patients with non–small cell lung cancer (NSCLC) would benefit from treatment with immune checkpoint inhibitors (ICPIs). Objectives: The purpose of this study was to draw a detailed time to treatment failure (TTF) curve with information on the changes in peripheral eosinophil expression during ICPI treatment for NSCLC, and to clarify whether eosinophil expression can predict prolonged TTF. Patients and methods: In 259 patients with NSCLC treated with ICPI therapy, peripheral eosinophil counts and percentages at the time of each ICPI administration were evaluated from the beginning of ICPI treatment up to TTF. Univariable and multivariable analyses were performed to identify clinical factors associated with TTF. Results: Patients receiving ICPI monotherapy (n = 180) were divided into 3 groups (TTF ≤6 weeks, TTF >6 weeks and ≤24 weeks, and TTF >24 weeks) and the number of patients with an eosinophil percentage of 5% or more within 6 weeks of ICPI therapy initiation was significantly different among these groups. In univariable and multivariable analyses, performance status of 0 to 1, immune-related adverse event not requiring ICPI discontinuation as well as an eosinophil percentage of 5% or more and an eosinophil count of 330/μ or more within 6 weeks of ICPI therapy initiation were significant favorable factors for prolonged TTF. In patients treated with combination therapy of ICPI and chemotherapy (n = 79), the number of patients with an eosinophil percentage of 5% or more within 12 weeks of therapy initiation was significantly different between patients with a TTF of up to 12 weeks and those with a more prolonged TTF. However, the only significant favorable factor for TTF was female sex. Conclusions: In NSCLC patients treated with ICPI therapy, particularly ICPI monotherapy, eosinophil measurements during treatment might be useful for predicting prolonged TTF.

Gastrointestinal (GI) dysmotility is a common complication in acute, critically ill, postoperative, and chronic patients that may lead to impaired nutrient delivery, poor clinical, and patient-reported outcomes. Several pharmacological and nonpharmacological interventions to treat GI dysmotility were investigated in dozens of clinical studies. However, they often yielded conflicting results, at least in part, because various (nonstandardized) definitions of GI dysmotility were used and methodological quality of studies was poor. While a universally accepted definition of GI dysmotility is yet to be developed, a systematic analysis of data derived from double-blind placebo-controlled randomized trials may provide robust data on absolute and relative effectiveness of various interventions as the study outcome (GI motility) was assessed in the least biased manner.To systematically review data from double-blind placebo-controlled randomized trials to determine and compare the effectiveness of interventions that affect GI motility.Three electronic databases (MEDLINE, SCOPUS, and EMBASE) were searched. A random effects model was used for meta-analysis. The summary estimates were reported as mean difference (MD) with the corresponding 95% confidence interval (CI).A total of 38 double-blind placebo-controlled randomized trials involving 2371 patients were eligible for inclusion in the systematic review. These studies investigated a total of 20 different interventions, of which 6 interventions were meta-analyzed. Of them, the use of dopamine receptor antagonists (MD, −8.99; 95% CI, −17.72 to −0.27; P = 0.04) and macrolides (MD, −26.04; 95% CI, −51.25 to −0.82; P = 0.04) significantly improved GI motility compared with the placebo group. The use of botulism toxin significantly impaired GI motility compared with the placebo group (MD, 5.31; 95% CI, −0.04 to 10.67; P = 0.05). Other interventions (dietary factors, probiotics, hormones) did not affect GI motility.Based on the best available data and taking into account the safety profile of each class of intervention, dopamine receptor antagonists and macrolides significantly improve GI motility and are medications of choice in treating GI dysmotility.

High-Dose Oral Erythromycin Decreased the Incidence of Parenteral Nutrition-Associated Cholestasis in Preterm Infants

Recently the American Gastroenterological Association published a medical position statement on the clinical use of esophageal manometry (1), accompanied by a technical review (2). These documents are a comprehensive description of basic esophageal physiology and manometry, technical aspects and limitations of manometric recordings, and the clinical applications of esophageal manometry in the adult patient. Because the approach to the child with esophageal disorders is different, the North American Society for Pediatric Gastroenterology and Nutrition has prepared the following medical position statement. ESOPHAGEAL PHYSIOLOGY IN CHILDREN Swallowing is a complex process initiated by the voluntary ingestion of food and followed by the involuntary or automatic actions of the oropharynx and the esophagus. The esophageal phase of the swallow involves the transport of the food bolus into the stomach. The three structural components of the esophagus are the upper esophageal sphincter (UES), the esophageal body, and the lower esophageal sphincter (LES) (3). The UES, defined as an area of increased pressure between the pharynx and the esophageal body, is present by at least 32 weeks gestation and is functional at birth (4). However, swallowing coordination may be poor in the first week of life and in premature infants <1500 g (4-6). Structurally, the UES is ≈0.5-1 cm long at birth and increases in length to ≈3 cm in the adult (3). In general, the UES corresponds to the cricopharyngeus muscle, the inferior pharyngeal constrictor, and the muscle of the proximal esophagus. Surgical myotomy of the cricopharyngeus does not abolish UES tone (7-9). Because of axial movement of the UES, its precise pressure measurement requires a special sleeve catheter; with such a catheter UES pressure ranges between 18 and 44 cm H2O (7). UES location can be determined by side-port catheters for the purpose of placing proximal esophageal pH electrodes. The esophageal body is composed of striated muscle in the upper one-third and smooth muscle in the distal two-thirds. Three types of esophageal contractions occur: primary, secondary, and tertiary (3). Primary peristalsis begins after swallowing, in coordination with pharyngeal contraction and UES and LES relaxation. Secondary peristalsis occurs secondary to intraluminal distention, usually by the food bolus. This function is important in esophageal clearance of material such as refluxed gastric contents. Tertiary contractions consist of random, spontaneous contractions that have no peristaltic function. Pressures within the esophageal body vary with respiration. The velocity of csophageal contractions is typically from 2 to 5 cm per second but is slower during the first week of life, ranging from 0.8 to 2 cm per second.3 The LES is the high-pressure zone between the esophageal body and the stomach. Like the UES, its length increases with age, from 1 cm in the newborn to 2-4 cm in the adult (10,11). LES pressure also varies with age, ranging from 7 mm Hg in a premature infant of 27 weeks gestation to 18 mm Hg at term and from 10 to 45 mm Hg in the adult (1,12). CLINICAL CONSIDERATIONS Typical manifestations of abnormal esophageal function in the child are eating difficulties, pain, or regurgitation. Since the esophagus is composed of both striated and smooth muscle, abnormalities of esophageal motility can involve either muscle type or both. Disorders of esophageal function can be either primary or secondary to systemic disease. The symptoms and signs that most commonly suggest a disorder of swallowing or esophageal function in children are dysphagia (including food refusal, abnormally slow eating, persistent drooling, and posturing during swallow (13), chest pain or odynophagia, recurrent aspiration, and recurrent food impaction. Achalasia and chronic intestinal pseudo-obstruction are the most common primary esophageal motility disorders in children, but both occur infrequently. Diffuse esophageal spasm and nutcracker esophagus occur rarely. Esophageal motility may also be abnormal secondary to reflux esophagitis and tracheo-esophageal fistula, although esophageal manometry has little or no role in the evaluation of these disorders. Pharyngeal and cricopharyngeal motor dysfunction may be of several origins, which may be classified as follows: (a) corticobulbar disorders, such as palsies, Arnold-Chiari malformation, stroke, tumor, trauma, and multiple sclerosis; (b) neuropathic disorders, such as diabetes, tetanus, lead poisoning, rabies, and drug reactions (e.g., nitrazepam); (c) motor end plate disease, such as myasthenia gravis and botulism; (d) myopathic disorders, such as muscular dystrophy, collagen vascular diseases, hyperthyroidism and hypothyroidism; and (e) autonomic disorders, such as familial dysautonomia. Measurement of esophageal contraction allows differentiation of some of these disorders. Generally, esophageal manometry is performed after a radiographic contrast study or upper endoscopy of the esophagus has excluded structural or other causes of esophageal dysfunction. It can be performed to evaluate nonstructural abnormalities of the esophagus, such as achalasia; disorders of connective tissue, such as scleroderma; and chronic intestinal pseudo-obstruction or to determine the location of the sphincters for esophageal pH monitoring (14-16). TECHNICAL CONSIDERATIONS Esophageal manometry is performed differently in children than in adults because of the differences in size of the esophagus, cooperation by the patient, and neurologic and developmental maturation. These differences require special equipment as well as technical expertise to perform the study, handle the patient, and properly interpret the findings. Two types of catheter are available: water-perfused and solid-state. When water-perfused catheters are used in small infants, fewer recording ports are utilized to reduce the diameter of the catheter, which is typically 6-10 French (2-3 mm). Such a small catheter size must be accounted for in the amplitude and duration of waves. Solid-state catheters offer several advantages in the pediatric patient, such as a more rapid response rate, maintenance of transducer and lumen relationship in the upright position, and lack of spontaneous stimulation of swallows by water. However, cost, fragility, and inflexibility are significant disadvantages that preclude routine usage. The spacing of the sensing ports depends on the size of the patient. The interval between perfusion ports or transducers may need to be as close as 1-3 cm apart to accommodate the shorter esophagus in infants. For precise pressure measurements, the low-compliance perfusion system must be adapted to children. During perfusion in infants and small children, the perfusion rate may need to be slower because of the size of the esophagus, the fluid tolerance of infants, and the potential for aspiration. Care must be exercised to compensate for the slower flow rate by decreasing the system compliance. While such precise accounting of compliance and flow rate is required for research, it is not necessary for most clinical purposes. Esophageal manometry is best performed without sedation. In many children, however, sedation is necessary. Midazolam and chloral hydrate have been shown to be effective with minimal or no influence on pressure measurements (17,18). A natural reflex swallow may be induced in young infants and neurologically abnormal children by gently blowing in the child's face (Santmyer swallow) (19). At least the distal sensing site should be advanced into the stomatch initially (20-23). The single most difficult technical aspect of esophageal manometry in children is cooperation. Physicians performing manometry in children must have great patience. The patient's cooperation can, however, be improved by the use of age-appropriate relaxation techniques. For example, infants relax with swaddling and use of a pacifier. Toddlers are comforted by having a favorite blanket or toy. School-age children benefit from being allowed to handle and examine equipment before the procedure. Adolescents benefit from a thorough review of what to expect before the procedure. Recording artifacts are common in the pediatric patient and occur more commonly than in adults. Specific behaviors (e.g., crying or squirming) should be noted on the tracing itself to allow proper interpretation upon completion of the study. RECOMMENDATIONS The following recommendations were prepared with the critique and endorsement of the Subcommittee on Endoscopy and Procedures, the approval of the Patient Care Committee, review by the NASPGN membership at large, and the authorization of the Executive Council of NASPGN. These recommendations are subject to change of the basis of periodic review of subsequent research. Esophageal manometry can be useful to evaluate symptoms or signs of esophageal dysfunction, such as dysphagia, odynophagia, chest pain, aspiration, and recurrent food impaction. Contrast radiography and/or endoscopy of the esophagus is generally performed prior to manometry. Esophageal manometry can be useful to diagnose motility disorders of the esophagus such as achalasia as well as to detect esophageal manifestations of disorders of connective tissue (such as scleroderma) and chronic intestinal pseudo-obstruction. Esophageal manometry can be useful to locate the upper and lower esophageal sphincters for esophageal pH monitoring. Esophageal manometry is generally not useful in the diagnosis or medical management of gastroesophageal reflux disease or structural lesions of the esophagus.

Abdominal pain is the most challenging symptom in chronic intestinal pseudoobstruction (CIPO) syndrome, because of its severity and the limited availability of suitable opioid formulations, especially in pediatric patients with digestive problems. Most of the children with CIPO cannot tolerate oral formulations. We present 4 cases of children with CIPO and severe intractable abdominal pain, and report on the use of a recently available form of opioid, transdermal buprenorphine in a dosage of 5 mcg/h. CIPO and the unique pharmacological profile of buprenorphine are reviewed briefly.

Chronic intestinal pseudo-obstruction (CIPO) is a rare intestinal motility disorder with significant morbidity and mortality in pediatric patients. The diagnosis of CIPO is difficult, because it is clinically based on the symptoms and signs of bowel obstruction which are similar to the clinical manifestations of other gastrointestinal diseases like short bowel syndrome (SBS). Therefore, it is desirable to identify and establish new laboratory diagnostic markers for CIPO that are reliable and easily accessible. In our study we have identified the ratio of the urinary glutamine and glutamic acid as a promising biomarker for distinguishing suspected CIPO cases and simple SBS cases. The area under ROC curve was 0.83, at cutoff value = 7.04 with sensitivity of 65% and specificity of 92%.

Although chronic intestinal pseudo-obstruction (CIPO) is a rare and extremely severe functional digestive disorder, its clinical course and severity show various patterns. We assessed small bowel peristalsis in CIPO patients using cine-MRI (video-motion MRI) and their clinical characteristics to evaluate the clinical importance of performing cine-MRI in patients with this intractable disease. The medical records of 131 patients referred to our institution with a suspected diagnosis of CIPO between 2010 and 2015 were retrospectively evaluated. Thirty-three patients (22 female/11 male; age range 16-79years) who met the criteria for CIPO and underwent cine-MRI were enrolled. Mean luminal diameter (MLD), contraction ratio (CR), and contraction cycle (CC) were determined and compared with these parameters in healthy volunteers. Clinical outcomes in patients with CIPO were also evaluated. The median follow-up time was 25.2months (range, 1-65months). Of the 33 patients with CIPO, 23 (70%) showed apparently disturbed small intestinal peristalsis, whereas 10 (30%) did not. The percentage of patients requiring intravenous alimentation was significantly higher (p=0.03), and the mean serum albumin level was significantly lower (p=0.04), in patients with than without impaired small intestinal peristalsis. Although both cine-MRI and CT findings in the latter ten cases were within the normal range, MLD and CR differed significantly from healthy volunteers. Cine-MRI is useful in predicting severe clinical features in patients with CIPO, and in detecting slightly impaired small contractility that cannot be detected on CT.

Chronic intestinal pseudo-obstruction (CIPO) is an extremely rare condition with symptoms of recurrent intestinal obstruction without any lesions. The outcomes of pediatric CIPO and predictors for the outcomes have not yet been well established. We analyzed the clinical outcomes and associated factors for the outcomes of pediatric CIPO. We retrospectively reviewed 66 primary CIPO patients diagnosed between January 1985 and December 2017. We evaluated parenteral nutrition (PN) factors such as PN duration, PN use over 6 months, home PN, and mortality as outcomes. We selected onset age, presence of urologic symptoms, pathologic type, and involvement extent as predictors. The early-onset CIPO was found in 63.6%, and 21.2% of the patients presenting with urologic symptoms. Of the 66 patients, 47 and 11 had neuropathy and myopathy, respectively. The generalized involvement type accounted for 83.3% of the cases. At the last follow-up, 24.2% of the patients required home PN management. The mean duration of PN was 11.8 ± 21.0 months. The overall mortality rate of primary CIPO was 18.2%. PN factors were predicted by the urologic symptoms and extent of involvement. However, mortality was predicted by pathologic type. The onset age was not significantly associated with the outcomes. CIPO with urologic symptoms and generalized CIPO had poor PN outcomes. Myopathy is suggested as a predictor of mortality in children with primary CIPO.

Introduction: Intestinal failure-associated liver disease (IFALD) develops in children dependent upon long-term parenteral nutrition (PN). Laboratory and radiographic abnormalities are characteristic of the disorder. Sonographic findings (SF) include steatosis, edema, and biliary stones/sludge. Steatosis seems more prevalent in adults, while cholestasis is more prominent in children. IFALD can progress to fibrosis, cirrhosis, and end-stage liver disease. Abdominal ultrasound is a cost-effective and non-invasive modality that can be useful in examining the liver of patients with intestinal failure (IF). The aim of this study is to review liver SF and their correlation with liver biochemistry tests (LT) in pediatric patients with IF. Methods: We retrospectively reviewed the charts of 163 pediatric IF patients followed at our Center between 1998-2016. We specifically reviewed demographics, etiology of IF, SF and liver biochemistry tests. Results: Sixty eligible patients were included in this analysis (median age: 2.3 years, range: 1 month-18 years, 52% male). IF was caused by necrotizing enterocolitis (42%), gastrointestinal dysmotility (23%), intestinal atresia (13%), gastroschisis (8%) and volvulus (8%). Forty-six of 60 patients had elevated LT. Thirty-nine patients (85%) were cholestatic, and 35 patients (76%) had abnormal SF: splenomegaly (57%), hepatomegaly (54%), increased liver echogenicity (37%), gallbladder sludge (23%), cholelithiasis (17%), and heterogeneous liver (17%). Seven of 14 (50%) patients with normal LT had abnormal SF: splenomegaly (57%), cholelithiasis (43%), increased liver echogenicity (14%), and gallbladder sludge (14%). Conclusion: Abnormal SF were present in most pediatric IF patients with elevated LT and in half of the patients with normal LT. Increased liver echogenicity, suggestive of hepatic steatosis or edema, was more prevalent in children with IF than expected. Based on our single-center experience, we recommend the routine use of sonographic screening in pediatric patients with IF, regardless of LT, to achieve early detection and treatment of IFALD.

Su1989 - Severe Gastrointestinal Dysmotility Related Intestinal Failure: Chronic Intestinal Pseudo-Obstruction, Enteric Dysmotility or a ‘Pragmatic’ Approach? Experience from a UK National Referral Centre

BackgroundChronic intestinal pseudo-obstruction (CIPO) is a rare and severe disorder presenting with the clinical and radiological features of intestinal obstruction in the absence of a mechanical cause. When it manifests in children, it is referred to as pediatric intestinal pseudo-obstruction (PIPO). Diagnosis remains challenging and is largely based on exclusion. Management is primarily symptomatic, and among the available therapeutic approaches, cholinesterase inhibitors have emerged as potential options for severe gastrointestinal dysmotility, particularly when conventional treatments are insufficient. This review summarizes the current evidence on the use of pyridostigmine and neostigmine in CIPO, with a focus on pediatric patients.MethodsA systematic review was performed using PubMed, Embase, Web of Science, and Scopus, including all studies published up to July 2025 that evaluated the use of pyridostigmine and neostigmine in pediatric patients with CIPO.ResultsOur review identified 22 publications reporting a total of 54 patients. Overall, treatment with neostigmine or pyridostigmine was associated with a favorable clinical response in approximately two-thirds of cases, ranging from partial improvement to complete symptoms resolution. Safety outcomes were generally reassuring, with few adverse events and only rare cases requiring treatment discontinuation.DiscussionPyridostigmine and neostigmine may represent therapeutic options for pediatric CIPO, with neostigmine appearing particularly effective in acute settings and pyridostigmine more suited to chronic management. Although current evidence supports both safety and potential efficacy, robust clinical trials are essential before these agents can be integrated into standard care protocols.Supplementary InformationThe online version contains supplementary material available at 10.1007/s40272-025-00736-z.

Early Intervention and Resolution of Pediatric Intestinal Pseudo-Obstruction in Systemic Lupus Erythematosus: A Pediatric Case Report