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Aims/hypothesis: Diabetic gastroenteropathy frequently causes debilitating gastrointestinal symptoms. Previous uncontrolled studies have shown that transcutaneous vagal nerve stimulation (tVNS) may improve gastrointestinal symptoms. To investigate the effect of cervical tVNS in individuals with diabetes suffering from autonomic neuropathy and gastrointestinal symptoms, we conducted a randomised, sham-controlled, double-blind (participants and investigators were blinded to the allocated treatment) study. Methods: This study included adults (aged 20–86) with type 1 or 2 diabetes, gastrointestinal symptoms and autonomic neuropathy recruited from three Steno Diabetes Centres in Denmark. Participants were randomly allocated 1:1 to receive active or sham stimulation. Active cervical tVNS or sham stimulation was self-administered over two successive study periods: 1 week of four daily stimulations and 8 weeks of two daily stimulations. The primary outcome measures were gastrointestinal symptom changes as measured using the gastroparesis cardinal symptom index (GCSI) and the gastrointestinal symptom rating scale (GSRS). Secondary outcomes included gastrointestinal transit times and cardiovascular autonomic function. Results: Sixty-eight participants were randomised to the active group, while 77 were randomised to the sham group. Sixty-three in the active and 68 in the sham group remained for analysis in study period 1, while 62 in each group were analysed in study period 2. In study period 1, active and sham tVNS resulted in similar symptom reductions (GCSI: −0.26 ± 0.64 vs −0.17 ± 0.62, p=0.44; GSRS: −0.35 ± 0.62 vs −0.32 ± 0.59, p=0.77; mean ± SD). In study period 2, active stimulation also caused a mean symptom decrease that was comparable to that observed after sham stimulation (GCSI: −0.47 ± 0.78 vs −0.33 ± 0.75, p=0.34; GSRS: −0.46 ± 0.90 vs −0.35 ± 0.79, p=0.50). Gastric emptying time was increased in the active group compared with sham (23 min vs −19 min, p=0.04). Segmental intestinal transit times and cardiovascular autonomic measurements did not differ between treatment groups (all p>0.05). The tVNS was well-tolerated. Conclusions/interpretation: Cervical tVNS, compared with sham stimulation, does not improve gastrointestinal symptoms among individuals with diabetes and autonomic neuropathy. Trial registration: ClinicalTrials.gov NCT04143269 Funding: The study was funded by the Novo Nordisk Foundation (grant number NNF180C0052045) [ABSTRACT FROM AUTHOR]

Congenital anomalies of the kidney and urinary tract (CAKUT) are estimated to be responsible for 20%–50% of congenital anomalies and are also a leading etiology of early‐onset renal disease. Primary CAKUT are caused by genetic factors that impair proper in‐utero genitourinary tract development and secondary CAKUT result from the influence of environmental factors. The CHRNA3 gene, which encodes the Alpha‐3 subunit of the nicotinic acetylcholine receptor, is hypothesized to be associated with Megacystis‐microcolon‐intestinal hyperperistalsis syndrome. More recently, pathogenic variants in CHRNA3 have been identified in individuals with CAKUT as well as individuals with panautonomic failure. Here we present a patient with neurogenic bladder, vesicoureteral reflux, mydriasis, and gastrointestinal dysmotility found to have novel compound heterozygous variants in CHRNA3. These findings support the consideration of CHRNA3 disruption in the differential for CAKUT with dysautonomia and gastrointestinal dysmotility. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Purpose of Review: To discuss all the various motility disorders impacting people with Cystic Fibrosis (PwCF) and provide diagnostic and management approaches from a group of pediatric and adult CF and motility experts and physiologists with experience in the management of this disease. Recent Findings: Gastrointestinal (GI) symptoms coexist with pulmonary symptoms in PwCF regardless of age and sex. The GI manifestations include gastroesophageal reflux disease, esophageal dysmotility gastroparesis, small bowel dysmotility, small intestinal bacterial overgrowth syndrome, distal idiopathic obstruction syndrome, constipation, and pelvic floor disorders. They are quite debilitating, limiting the patients' quality of life and affecting their nutrition and ability to socialize. This genetic disorder affects many organ systems and is chronic, potentially impacting fertility and future family planning, requiring a multidisciplinary approach. Summary: Our review discusses the treatments of motility disorders in CF, their prevalence and pathophysiology. We have provided a framework for clinicians who care for these patients that can help to guide their clinical management. [ABSTRACT FROM AUTHOR]

Background: Metoclopramide and domperidone are prokinetic agents commonly used to treat gastrointestinal dysmotility disorders. This study aimed to evaluate the safety and associated side effects of prolonged-use metoclopramide and domperidone as treatment for chronic gastrointestinal dysmotility disorders in patients with systemic sclerosis (SSc). Methods: A quantitative observational survey was conducted by interview questionnaire in rheumatology outpatients at a tertiary teaching hospital in Riyadh, Saudi Arabia. The study included all patients aged 25–80 years diagnosed with SSc. All patients were on metoclopramide or domperidone for the treatment of chronic gastrointestinal dysmotility symptoms over at least 12 weeks. Results: Eighteen eligible patients were included. Most study participants were diagnosed with SSc complicated by interstitial lung disease (n = 13; 72.2 %). The most frequently reported side effect that occurred while taking prokinetic drugs was shortness of breath (n = 12; 66.7 %). None of the participants reported experiencing depression, galactorrhea, or syncope. CNS side effects were reported in 5.6 %. There were no differences in side effects based on the type and dosage of prokinetic drug used. Conclusions: Use of metoclopramide and domperidone for the treatment of chronic gastrointestinal dysmotility in SSc patients for 12 weeks or longer was not associated with any troublesome side effects. Further studies with more participants are needed to confirm our findings.

Critical illness may disrupt nutritional, protective, immune, and endocrine functions of the gastrointestinal tract, leading to a state of gastrointestinal dysmotility. We aimed to identify factors associated with the occurrence of gastrointestinal dysmotility in critically ill patients. A cross-sectional retrospective study was conducted, using patient files as a source of data. The study included 185 critically ill patients treated in the intensive care unit of the University Clinical Center, Kragujevac, Serbia, from January 1, 2016, to January 1, 2022. Significant risk factors associated with some form of gastrointestinal dysmotility were acute kidney injury (with paralytic ileus, nausea, vomiting, and constipation), recent abdominal surgery (with ileus, nausea, vomiting, and constipation), mechanical ventilation (with ileus, and nausea), age (with ileus and constipation), and use of certain medication such as opioids (with ileus, gastro-esophageal reflux, nausea, vomiting, and constipation), antidepressants (with ileus, nausea, and vomiting), and antidiabetics (with ileus). On the other hand, Charlson comorbidity index had divergent effects, depending on the form of gastrointestinal dysmotility: it increased the risk of gastro-esophageal reflux but protected against ileus, nausea, and vomiting. In clonclusion, recognition of factors associated with gastrointestinal dysmotility should initiate preventative measures and, thus, accelerate the recovery of critically ill.

Gastrointestinal (GI) symptoms are highly prevalent among individuals with autism spectrum disorder (ASD), but the molecular link between ASD and GI dysfunction remains poorly understood. The enteric nervous system (ENS) is critical for normal GI motility and has been shown to be altered in mouse models of ASD and other neurological disorders. Contactin-associated protein-like 2 (Cntnap2) is an ASDrelated synaptic cell-adhesion molecule important for sensory processing. In this study, we examine the role of Cntnap2 in GI motility by characterizing Cntnap2’s expression in the ENS and assessing GI function in Cntnap2 mutant mice. We find Cntnap2 expression predominately in enteric sensory neurons. We further assess in vivo and ex vivo GI motility in Cntnap2 mutants and show altered transit time and colonic motility patterns. The overall organization of the ENS appears undisturbed. Our results suggest that Cntnap2 plays a role in GI function and may provide a molecular link between ASD and GI dysfunction. [ABSTRACT FROM AUTHOR]

Gastrointestinal (GI) symptoms are highly prevalent among individuals with autism spectrum disorder (ASD), but the molecular link between ASD and GI dysfunction remains poorly understood. The enteric nervous system (ENS) is critical for normal GI motility and has been shown to be altered in mouse models of ASD and other neurological disorders. Contactin-associated protein-like 2 (Cntnap2) is an ASD-related synaptic cell-adhesion molecule important for sensory processing. In this study, we examine the role of Cntnap2 in GI motility by characterizing Cntnap2’s expression in the ENS and assessing GI function in Cntnap2 mutant mice. We find Cntnap2 expression predominately in enteric sensory neurons. We further assess in vivo and ex vivo GI motility in Cntnap2 mutants and show altered transit time and colonic motility patterns. The overall organization of the ENS appears undisturbed. Our results suggest that Cntnap2 plays a role in GI function and may provide a molecular link between ASD and GI dysfunction.

Gastrointestinal dysmotility in systemic sclerosis occurs as the end result of extensive fibrosis of the gastrointestinal tract. The entire length of the tract from the esophagus to the anorectum could be affected, exerting various gastrointestinal symptoms. Clinical manifestations attributed to gastrointestinal dysmotility are associated with significant distress and an increased risk of nutritional impairment, reducing the quality of life of systemic sclerosis patients. One of the most commonly overlooked gastrointestinal implications in systemic sclerosis is malnutrition. Once malnutrition ensues in the course of systemic sclerosis, the detrimental effects attributed to nutritional decline are difficult to reverse and pose an increased risk of mortality. Adequate management through timely diagnosis of gastrointestinal dysmotility and utilization of malnutrition screening tools for systemic sclerosis patients could prevent the progression to malnutrition and its negative impacts. [ABSTRACT FROM AUTHOR]

Abstract Background Acute pancreatitis is a serious threat to human health and gastrointestinal dysmotility is a common complication for acute pancreatitis patients, resulting in delayed feeding, oral feeding intolerance, paralytic ileus, and abdominal compartment syndrome. Currently, there are limited treatment for this complication. Neostigmine is known to increase gastrointestinal motility and has been used to treat gastrointestinal dysmotility after surgery. However, research in treating acute pancreatitis with neostigmine is currently limited. Methods This trial is a randomized, placebo-controlled, double-blinded, mono-centric trial that will test the hypothesis that neostigmine can improve gastrointestinal motility in patients with severe acute pancreatitis. Up to 56 patients will be randomized in this study receiving 0.5 mg/1 ml of neostigmine methylsulfate injection twice per day or 1 ml of saline injection twice per day. Defection time (aim 1), mortality and organ failure (aim 2), borborygmus, starting of enteral nutrition and intra-abdominal pressure (aim 3), and length of ICU and hospital stay (aim 4) will be assessed. Discussion Findings from this study will provide data supporting the usage of neostigmine for treating severe acute pancreatitis patients with gastrointestinal dysmotility. Trial registration This study is registered on chictr.org.cn with the identifier as ChiCTR2200058305. Registered on April 5, 2022.

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.

Intestinal motility disorders represent a frequent problem in children with neurological impairment. These conditions are characterized by abnormal movements of the gut, which can result in symptoms such as constipation, diarrhea, reflux, and vomiting. The underlying mechanisms leading to dysmotility are various, and the clinical manifestations are often nonspecific. Nutritional management is an important aspect of care for children with gut dysmotility, as it can help to improve their quality of life. Oral feeding, when safe and in the absence of risk of ingestion or severe dysphagia, should always be encouraged. When oral nutrition is insufficient or potentially harmful, it is necessary to switch to an enteral by tube or parenteral nutrition before the onset of malnutrition. In most cases, children with severe gut dysmotility may require feeding via a permanent gastrostomy tube to ensure adequate nutrition and hydration. Drugs may be necessary to help manage gut dysmotility, such as laxatives, anticholinergics and prokinetic agents. Nutritional management of patients with neurological impairment often requires an individualized care plan to optimize growth and nutrition and to improve overall health outcomes. This review tries to sum up most significant neurogenetic and neurometabolic disorders associated with gut dysmotility that may require a specific multidisciplinary care, identifying a proposal of nutritional and medical management. [ABSTRACT FROM AUTHOR]

Background: Acute pancreatitis is a serious threat to human health and gastrointestinal dysmotility is a common complication for acute pancreatitis patients, resulting in delayed feeding, oral feeding intolerance, paralytic ileus, and abdominal compartment syndrome. Currently, there are limited treatment for this complication. Neostigmine is known to increase gastrointestinal motility and has been used to treat gastrointestinal dysmotility after surgery. However, research in treating acute pancreatitis with neostigmine is currently limited. Methods: This trial is a randomized, placebo-controlled, double-blinded, mono-centric trial that will test the hypothesis that neostigmine can improve gastrointestinal motility in patients with severe acute pancreatitis. Up to 56 patients will be randomized in this study receiving 0.5 mg/1 ml of neostigmine methylsulfate injection twice per day or 1 ml of saline injection twice per day. Defection time (aim 1), mortality and organ failure (aim 2), borborygmus, starting of enteral nutrition and intra-abdominal pressure (aim 3), and length of ICU and hospital stay (aim 4) will be assessed. Discussion: Findings from this study will provide data supporting the usage of neostigmine for treating severe acute pancreatitis patients with gastrointestinal dysmotility. Trial registration: This study is registered on chictr.org.cn with the identifier as ChiCTR2200058305. Registered on April 5, 2022. [ABSTRACT FROM AUTHOR]

Intestinal motility disorders represent a frequent problem in children with neurological impairment. These conditions are characterized by abnormal movements of the gut, which can result in symptoms such as constipation, diarrhea, reflux, and vomiting. The underlying mechanisms leading to dysmotility are various, and the clinical manifestations are often nonspecific. Nutritional management is an important aspect of care for children with gut dysmotility, as it can help to improve their quality of life. Oral feeding, when safe and in the absence of risk of ingestion or severe dysphagia, should always be encouraged. When oral nutrition is insufficient or potentially harmful, it is necessary to switch to an enteral by tube or parenteral nutrition before the onset of malnutrition. In most cases, children with severe gut dysmotility may require feeding via a permanent gastrostomy tube to ensure adequate nutrition and hydration. Drugs may be necessary to help manage gut dysmotility, such as laxatives, anticholinergics and prokinetic agents. Nutritional management of patients with neurological impairment often requires an individualized care plan to optimize growth and nutrition and to improve overall health outcomes. This review tries to sum up most significant neurogenetic and neurometabolic disorders associated with gut dysmotility that may require a specific multidisciplinary care, identifying a proposal of nutritional and medical management.

Abstract Background Allied disorders of Hirschsprung’s disease (ADHD) mainly present with bowel obstruction, intestinal dilatation, and chronic constipation, while recurrent spontaneous pneumoperitoneum was rarely reported. We aimed to report a case of recurrent spontaneous pneumoperitoneum caused by ADHD. Case presentation A 59-year-old female patient presented with progressive and severe constipation in the past 30 years. She suffered from abdominal discomfort, which was described as ‘gurgling’ during the last three years. Radiography showed free-air and intestinal dilatation, without any other diseases, and she was identified with recurrent spontaneous pneumoperitoneum. Gastrointestinal transit test indicated gastrointestinal motility disorder, and anorectal manometry confirmed the presence of rectal anus-suppressing reflex. Subtotal colectomy was performed to relieve apparent constipation, and the postoperative pathological examination of the colon demonstrated proliferation of nerve fibers and hyperplasia of myenteric plexuses, as well as a relatively scarcity of ganglion cells in the myenteric plexus. Based on the presentations and the postoperative pathology, she was diagnosed with ADHD. The recurrent spontaneous pneumoperitoneum was regarded as the gas escape from dilated intestines, which was in high pressure. All the symptoms and her mental state were improved after the treatment with gastrointestinal decompression and enteral nutrition. However, during follow-up visits, she had intestinal infection, and suffered from severe diarrhea and water-electrolyte imbalance, and the patient eventually died at 17 months after the diagnosis. Conclusion ADHD could be a rare cause of recurrent spontaneous pneumoperitoneum, and are mainly undiagnosed or misdiagnosed. A full-thickness biopsy of the gastrointestinal tract (especially the small intestine and sigmoid colon) and differential diagnosis are recommended for the definitive diagnosis. While the ADHD have shown a poor prognosis, timely and long-term treatment with intestinal decompression and nutritional therapy could help relieve symptoms and provide a better quality of life for such patients.

Background: Simultaneous measurement of gastrointestinal transit time (GITT) and plasma levodopa concentration (PLC) is crucial to understanding the effect of dysfunctional motility on levodopa response in patients with Parkinson's disease (PwPD). Objective: The aim is to determine if altered segmental GITT correlates with clinical response and PLC variability in PwPD. Methods: Ten typical and 10 erratic responders ingested the SmartPill (SP) wireless motility capsule. Serial PLC and finger tapping, obtained every 30 minutes for 3 hours after SP/levodopa ingestion, evaluated the correlation between GITT, clinical response, and PLC. Glucose breath testing assessed small intestinal bacterial overgrowth (SIBO). Results: GITT was not significantly different in "typical" and "erratic" responders. SIBO was positive in half of the erratic and negative in most typical responders. Conclusion: SP is a feasible technology for assessing GITT in PwPD. A larger study may be able to significantly differentiate/correlate GITT in different segments of the GI tract with response to levodopa. © 2022 International Parkinson and Movement Disorder Society. [ABSTRACT FROM AUTHOR]

Background and Aims: Gastrointestinal (GI) dysmotility is a common and debilitating clinical manifestation in patients with mitochondrial DNA (mtDNA)–related disease with no curative and few effective symptomatic therapies. A low-residue diet (LRD) has been shown to be effective at reducing bowel urgency, pain, and distension in functional GI-related conditions. We assessed tolerability and effects of an LRD on bowel habits in patients with mtDNA-related disease. Methods: This was a 12-week single-arm pilot study in patients with genetically determined primary mtDNA-related disease, meeting the ROME III constipation criteria. The co-primary outcomes were tolerability of an LRD (

Background: Allied disorders of Hirschsprung's disease (ADHD) mainly present with bowel obstruction, intestinal dilatation, and chronic constipation, while recurrent spontaneous pneumoperitoneum was rarely reported. We aimed to report a case of recurrent spontaneous pneumoperitoneum caused by ADHD.Case Presentation: A 59-year-old female patient presented with progressive and severe constipation in the past 30 years. She suffered from abdominal discomfort, which was described as 'gurgling' during the last three years. Radiography showed free-air and intestinal dilatation, without any other diseases, and she was identified with recurrent spontaneous pneumoperitoneum. Gastrointestinal transit test indicated gastrointestinal motility disorder, and anorectal manometry confirmed the presence of rectal anus-suppressing reflex. Subtotal colectomy was performed to relieve apparent constipation, and the postoperative pathological examination of the colon demonstrated proliferation of nerve fibers and hyperplasia of myenteric plexuses, as well as a relatively scarcity of ganglion cells in the myenteric plexus. Based on the presentations and the postoperative pathology, she was diagnosed with ADHD. The recurrent spontaneous pneumoperitoneum was regarded as the gas escape from dilated intestines, which was in high pressure. All the symptoms and her mental state were improved after the treatment with gastrointestinal decompression and enteral nutrition. However, during follow-up visits, she had intestinal infection, and suffered from severe diarrhea and water-electrolyte imbalance, and the patient eventually died at 17 months after the diagnosis.Conclusion: ADHD could be a rare cause of recurrent spontaneous pneumoperitoneum, and are mainly undiagnosed or misdiagnosed. A full-thickness biopsy of the gastrointestinal tract (especially the small intestine and sigmoid colon) and differential diagnosis are recommended for the definitive diagnosis. While the ADHD have shown a poor prognosis, timely and long-term treatment with intestinal decompression and nutritional therapy could help relieve symptoms and provide a better quality of life for such patients. [ABSTRACT FROM AUTHOR]

Background/Aims: Gastrointestinal (GI) dysmotility in acute pancreatitis (AP) aggravates inflammation and results in severe complications. This study aimed to explore effects and possible mechanisms of transcutaneous electrical acustimulation (TEA) on abdominal pain, GI dysmotility, and inflammation in AP patients. Methods: Forty‐two AP patients were blindly randomized to receive TEA (n = 21) at acupoints PC6 and ST36 or Sham‐TEA (n = 21) at sham points for 2 days. Symptom scores, gastric slow waves, autonomic functions (assessed by spectral analysis of heart rate variability), circulatory levels of motilin, ghrelin, and TNF‐α were measured before and after the treatment. Sixteen healthy controls (HCs) were also included without treatment for the assessment of gastric slow waves and biochemistry. Key Results: Compared with Sham‐TEA, TEA decreased abdominal pain score (2.57 ± 1.78 vs. 1.33 ± 1.02, p < 0.05), bloating score (5.19 ± 1.21 vs. 0.76 ± 0.99, p < 0.001), the first defecation time (65.79 ± 19.51 h vs. 51.38 ± 17.19 h, p < 0.05); TEA, but not Sham‐TEA, improved the percentage of normal gastric slow waves by 41.6% (p < 0.05), reduced AP severity score (5.52 ± 2.04 vs. 3.90 ± 1.90, p < 0.05) and serum TNF‐α (7.59 ± 4.80 pg/ml vs. 4.68 ± 1.85 pg/ml, p < 0.05), and upregulated plasma ghrelin (0.85 ± 0.96 ng/ml vs. 2.00 ± 1.71 ng/ml, p = 0.001) but not motilin (33.08 ± 22.65 pg/ml vs. 24.12 ± 13.95 pg/ml, p > 0.05); TEA decreased sympathetic activity by 15.0% and increased vagal activity by 18.3% (both p < 0.05). Conclusions & Inferences: TEA at PC6 and ST36 administrated at early stage of AP reduces abdominal pain, improves GI motility, and inhibits inflammatory cytokine, TNF‐α, probably mediated via the autonomic and ghrelin mechanisms. [ABSTRACT FROM AUTHOR]

Metoclopramide and domperidone are prokinetic agents commonly used to treat gastrointestinal dysmotility disorders. This study aimed to evaluate the safety and associated side effects of prolonged-use metoclopramide and domperidone as treatment for chronic gastrointestinal dysmotility disorders in patients with systemic sclerosis (SSc). A quantitative observational survey was conducted by interview questionnaire in rheumatology outpatients at a tertiary teaching hospital in Riyadh, Saudi Arabia. The study included all patients aged 25–80 years diagnosed with SSc. All patients were on metoclopramide or domperidone for the treatment of chronic gastrointestinal dysmotility symptoms over at least 12 weeks. Eighteen eligible patients were included. Most study participants were diagnosed with SSc complicated by interstitial lung disease (n = 13; 72.2 %). The most frequently reported side effect that occurred while taking prokinetic drugs was shortness of breath (n = 12; 66.7 %). None of the participants reported experiencing depression, galactorrhea, or syncope. CNS side effects were reported in 5.6 %. There were no differences in side effects based on the type and dosage of prokinetic drug used. Use of metoclopramide and domperidone for the treatment of chronic gastrointestinal dysmotility in SSc patients for 12 weeks or longer was not associated with any troublesome side effects. Further studies with more participants are needed to confirm our findings. [ABSTRACT FROM AUTHOR]

Keywords: Gastric antral vascular ectasia; Associated diseases; Gastrointestinal dysmotility; Vitamin D deficiency; Iron deficiency anemia; Gastroduodenal and intestinal permeability EN Gastric antral vascular ectasia Associated diseases Gastrointestinal dysmotility Vitamin D deficiency Iron deficiency anemia Gastroduodenal and intestinal permeability 3630 3634 5 09/21/21 20211001 NES 211001 Gastric antral vascular ectasia (GAVE) was described by Ryder in 1953 [[1]]. Associated diseases, Gastric antral vascular ectasia, Vitamin D deficiency, Iron deficiency anemia, Gastrointestinal dysmotility, Gastroduodenal and intestinal permeability Laboratory tests revealed severe iron deficiency anemia (IDA) and hypoalbuminemia-hemoglobin - 4.3 g/dl (13.5-18.0), iron - 3.5 µmol/l (10.6-28.3), albumin - 18.5 g/l (35-53), prothrombin time percentage activity (PT % activity) - 30.8%, (70-120), international normalized ratio (INR) - 2.38 (0.9-1.3). Although the relationship between vitamin D and GAVE-associated diseases has been studied, the direct link between vitamin D and GAVE has not been the subject of studies. [Extracted from the article]

Abstract Neuropathy should be considered as a possible etiological factor in patients with severe gastrointestinal symptoms, without signs of disease on routine investigations. Examinations of the autonomic and peripheral nervous systems may be helpful to select the patients who should be investigated with full‐thickness intestinal biopsy, and to give appropriate care.

Background: 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. Methods: 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. Results: 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). Conclusion: GI dysmotility occurs early in critically ill burn patients, and postpyloric feeding improves nutrition delivery. [ABSTRACT FROM AUTHOR]

5 Deleu D, Ebinger G, Michotte Y. Clinical and pharmacokinetic comparison of oral and duodenal delivery of levodopa/carbidopa in patients with Parkinson's disease with a fluctuating response to levodopa. Keywords: delayed gastric emptying; gastrointestinal dysmotility; Parkinson's disease; levodopa dose failure; motor fluctuations EN delayed gastric emptying gastrointestinal dysmotility Parkinson's disease levodopa dose failure motor fluctuations 394 396 3 04/05/22 20220401 NES 220401 Gastrointestinal involvement in Parkinson's disease (PD) can impact quality of life through disabling symptoms including nausea, early satiety, anorexia, and constipation and via disruption of oral levodopa absorption and motor and nonmotor fluctuations.1-3 Impaired gastric emptying (GE) may cause dose failures, delayed drug effect (delayed I on i ) and hence unpredictable dose responses.4,5 We report 2 patients with PD with striking examples of documented severe, prolonged upper gastrointestinal dysmotility to highlight this problem. Parkinson's disease, delayed gastric emptying, gastrointestinal dysmotility, levodopa dose failure, motor fluctuations. [Extracted from the article]

Gastroparesis is defined as a delay in gastric emptying in the absence of mechanical obstruction in the stomach. Gastroparesis has a number of causes, including postsurgical, secondary to medications, postinfectious, idiopathic, and as a complication of diabetes mellitus, where it is underrecognized. The cardinal symptoms of diabetic gastroparesis are nausea, early satiety, bloating, and vomiting. Diabetic gastroparesis is more common in females and has a cumulative incidence of 5% in type 1 diabetes and 1% in type 2 diabetes. It is associated with a reduction in quality of life and exerts a significant burden on health care resources. The pathophysiology of this disorder is incompletely understood. Diagnosis is made based on typical symptoms associated with the demonstration of delayed gastric emptying in the absence of gastric outlet obstruction. Gastric emptying scintigraphy is the gold standard for demonstrating delayed gastric emptying, but other methods exist including breath testing and the wireless motility capsule. Diabetic gastroparesis should be managed within a specialist multidisciplinary team, and general aspects involve dietary manipulations/nutritional support, pharmacological therapy, and surgical/endoscopic interventions. Specific pharmacological therapies include prokinetics and antiemetics, with several new medications in the drug development pipeline. Surgical/endoscopic interventions include botulinum toxin injection into the pylorus, gastric peroral endoscopic myotomy and gastric electrical stimulation. This article provides a detailed review and summary of the epidemiology, pathophysiology, investigation, and management of diabetic gastroparesis, and also gives an individual patient’s perspective of living with this disabling disorder.

A number of the well-recognized autoimmune and paraneoplastic neurologic syndromes commonly involve the autonomic nervous system. In some cases, the autonomic nerves or ganglia are primary targets of neurologic autoimmunity, as in immune-mediated autonomic ganglionopathies. In other disorders such as encephalitis, autonomic centers in the brain may be affected. The presence of autonomic dysfunction (especially gastrointestinal dysmotility) is sometimes overlooked even though this may contribute significantly to the symptom burden in these paraneoplastic disorders. Additionally, recognition of autonomic features as part of the clinical syndrome can help point the diagnostic evaluation toward autoimmune and paraneoplastic etiologies. As with other paraneoplastic disorders, the clinical syndrome and the presence and type of neurologic autoantibodies help to secure the diagnosis and direct the most appropriate investigation for malignancy. Optimal management for these conditions typically includes aggressive treatment of the neoplasm, immunomodulatory therapy, and symptomatic treatments for orthostatic hypotension and gastrointestinal dysmotility., (Copyright © 2024 Elsevier B.V. All rights are reserved, including those for text and data mining, AI training, and similar technologies.)

Small-bowel transit scintigraphy (SBTS) evaluates the accumulation of a radiolabeled meal in the terminal ileal reservoir (TIR) 6 h after ingestion. The location of the TIR may be difficult to determine because anatomic information is limited; for equivocal studies, the patient is asked to return the next day to help determine the TIR location by potential transit into the colon. The purpose of this study was to evaluate whether administration of an additional liquid-nutrient meal (LNM) at 6 h can promote movement of the radiolabeled meal to aid in the interpretation of SBTS and eliminate the need for the patient to return. Methods: This retrospective study reviewed 117 SBTS studies from February 2017 to September 2019. Patients were fed a standardized mixed radiolabeled solid-liquid meal for gastric emptying with SBTS according to Society of Nuclear Medicine and Molecular Imaging practice guidelines. An additional LNM was given at 6 h, and post-LNM images were obtained at least 20 min after the LNM. Two board-certified nuclear medicine physicians independently evaluated all images as equivocal or diagnostic at 6 h. Results: Of the 117 patients (71.8% female; median age, 42.0 y) undergoing SBTS, 37 were equivocal cases at 6 h before the LNM (31.6%; 95% CI, 23.3%-40.9%), compared with 12 equivocal cases after the LNM (10.3%; 95% CI, 5.4%-17.2%). Of the equivocal cases, 25 (69.4%; 95% CI, 51.9%-83.7%) had a definitive result after the LNM, whereas 11 (30.6%; 95% CI, 16.4%-48.1%) remained equivocal and 1 showed rapid transit. Among the 23 patients with gastroparesis, only 13 (57%) responded to the LNM, and none of the 3 patients with irritable bowel syndrome responded. Conclusion: The number of equivocal SBTS cases decreased after administration of an LNM at 6 h, converting to a definitive result. This suggests that with use of an LNM, most patients can complete SBTS in 1 d without the need for repeat imaging at 24 h. Administering an LNM appears to be less effective for patients with gastric disorders. However, the clinical significance remains to be explored, and it is unclear whether such patients have both a gastric and a small-bowel disorder, hence reducing any motility-promoting effect of the LNM. [ABSTRACT FROM AUTHOR]

Purpose: The Oral-anal Transit Test (OTT) is a simple method of obtaining information about colonic transit. We aim to assess the correlation of OTT with the neuromuscular integrity of the colon determined by colonic manometry (CM). Methods: All patients who had OTT followed by CM were evaluated. Less than 6 of 24 markers remaining on OTT was considered normal. CM was performed per previously published guidelines. A normal CM was defined as at least one High Amplitude Propagating Contraction progressing from the most proximal sensor through the sigmoid colon. Results: A total of 34 patients underwent both OTT and CM (44% male, age 4-18 years, mean 11.5 years, 97% functional constipation +/- soiling, Hirschsprung's Disease). Of normal and abnormal OTT patients, 85.7% (6/7) and 18.5% (5/27) respectively had normal CM. When all markers progressed to at least the sigmoid colon, this was 100% predictive against colonic inertia. Greater than 50% of patients with manometric isolated sigmoid dysfunction had markers proximal to the recto-sigmoid. Conclusion: OTT and CM are both valuable studies that assess different aspects of colonic function. OTT can be used as a screening test to rule out colonic inertia. However, the most proximal extent of remaining markers does not predict the anatomical extent of the manometric abnormality, particularly in isolated sigmoid dysfunction. [ABSTRACT FROM AUTHOR]

Purpose: This report describes the clinical manifestations of 35 patients sent to a University Immunology clinic with a diagnosis of fatigue and exercise intolerance who were identified to have low carnitine palmitoyl transferase activity on muscle biopsies. Recent Findings: All of the patients presented with fatigue and exercise intolerance and many had been diagnosed with fibromyalgia. Their symptoms responded to treatment of the metabolic disease. Associated symptoms included bloating, diarrhea, constipation, gastrointestinal reflux symptoms, recurrent infections, arthritis, dyspnea, dry eye, visual loss, and hearing loss. Associated medical conditions included Hashimoto thyroiditis, Sjogren's syndrome, seronegative arthritis, food hypersensitivities, asthma, sleep apnea, and vasculitis. Summary: This study identifies clinical features that should alert physicians to the possibility of an underlying metabolic disease. Treatment of the metabolic disease leads to symptomatic improvement. [ABSTRACT FROM AUTHOR]

Neuropathy should be considered as a possible etiological factor in patients with severe gastrointestinal symptoms, without signs of disease on routine investigations. Examinations of the autonomic and peripheral nervous systems may be helpful to select the patients who should be investigated with full‐thickness intestinal biopsy, and to give appropriate care. [ABSTRACT FROM AUTHOR]

Of these, only the ENS showed sex-specific changes, suggesting that the way in which the ENS plexuses responded to the same early life stress was sex-biased. The sex-specific nature of alterations in ENS and in the female-specific nature of dysmotility simulates an important feature of DGBI, where women seem to be more prone to developing gastrointestinal dysmotility disorders. Keywords: DGBI; dysbiosis; early life; enteric neurons; gastrointestinal dysmotility; sex-biased EN DGBI dysbiosis early life enteric neurons gastrointestinal dysmotility sex-biased 4251 4252 2 10/04/22 20221001 NES 221001 Disorders of gut-brain interaction (DGBI) afflict large numbers of people and are associated with gut dysfunctions including gastrointestinal dysmotility and altered stool frequency (Schmulson & Drossman, 2017). [Extracted from the article]

Neuromuscular diseases (NMDs) affect the development and growth of the neuromuscular system in children. The pathology can occur anywhere along the neuromuscular pathway, from the brain to the nerves to the muscle fibers. These diseases have a profound impact on the quality of life not only of children but also of their families. The predominant manifestation in NMDs is hypotonia, which leads to muscle weakness and fatigue, reduced mobility, and decreased physical performance. However, multiple organ systems can be affected, with resulting orthopedic, cardiac, infectious, respiratory, and nutritional problems. Children with NMD present an increased risk for several dietary and feeding difficulties because of their neuromuscular diagnosis, presentation, and severity. These problems include chronic gastrointestinal issues (constipation, dysphagia, gastroesophageal reflux, and diarrhea), dysphagia, malnutrition, and body composition alterations. As a result, compared to the overall pediatric population, infants and children with NMD are more likely to be malnourished, ranging from failure to thrive to overweight or obesity. Disease-specific guidelines vary in level of detail and recommendations for dietary management. Overall, nutritional data available are sparse, with the exception of Duchenne muscular dystrophy, spinal muscular atrophy, and congenital muscular dystrophy. The purpose of this review is to describe the spectrum of nutritional challenges in children with NMD and to summarize the main dietary and gastrointestinal recommendations for each neuromuscular disorder to provide guidance for daily clinical practice., Competing Interests: Conflict-of-interest statement: All the authors declare no conflict of interests for this article., (©The Author(s) 2023. Published by Baishideng Publishing Group Inc. All rights reserved.)

Abstract: Background: Gastrointestinal dysmotility (GID) covers a spectrum of disorders disrupting enteric neuromuscular co‐ordination which, when severe, causes intractable gastrointestinal symptoms and malnutrition and is a recognized cause of chronic intestinal failure. To date, no study has provided an in‐depth account of the experiences of patients with severe GID and their psychosocial needs. This study aimed to explore patients’ experiences from symptom onset and the process of seeking and receiving a diagnosis. It specifically explored the psychological effect of this process and the effect on relationships. Methods: Participants (n = 20, mean age = 47.9, female n = 16, parenteral nutrition = 13) were recruited from a UK center with tertiary Neurogastroenterology and Intestinal Failure services. A qualitative exploratory design with semi‐structured in‐depth interviews was used. Data were analyzed using thematic analysis. Key Results: Significant delays were experienced in obtaining a diagnosis. Participants reported having their mental health questioned and felt that they had to fight to prove their symptoms had a physical basis to access appropriate treatment. Although a diagnosis helped legitimize symptoms, the condition remained poorly understood by participants themselves, relatives, and health professionals. Participants discussed the impact that “feeling delegitimized” and the “lack of coherent understanding of GID” had on their relationships and mental health. Conclusions & Inferences: The distressing experience of GID symptoms are compounded by a delay in validating symptoms and lack of coherent understanding. More knowledge of GID is needed by health professionals to speed up diagnosis and offer more coherent information. The psychological impact of a GID diagnosis should be acknowledged early to help facilitate adjustment. [ABSTRACT FROM AUTHOR]

Purpose: To examine the prokinetic effect of clarithromycin in very low birth weight (VLBW) preterm infants.Materials and Methods: VLBW preterm infants who have not achieved half of the full enteral feeding in the second week of life were enrolled in the study. The infants enrolled in the study were randomized. Twenty infants received oral clarithromycin (7.5 mg/kg, twice a day) and 20 control infants did not receive any treatment.Results: Full enteral feeding was attained earlier in the clarithromycin group than in the control group [7 (6-9) versus 9 (9-11) days, respectively; p < .001]. Duration of parenteral nutrition and number of withheld feeds were significantly lower in the clarithromycin group (p = .013 and p < .001, respectively). Parenteral nutrition-associated cholestasis (n = 1 versus 3, p = .1) and length of hospital stay (50 versus 59 median days, p = .1) tend to be lower in the clarithromycin group without any statistical significance. We observed no adverse effect of clarithromycin therapy.Conclusions: Clarithromycin treatment in VLBW preterm infants resulted in better toleration of enteral feeding. Larger randomized controlled trials are needed to establish routine use of clarithromycin in the treatment of feeding intolerance. [ABSTRACT FROM AUTHOR]

Donohue syndrome is a rare congenital syndrome of insulin-resistance and abnormal glucose homeostasis, caused by mutations in the insulin receptor ( INSR) gene. It is characterized by specific phenotypic and clinical features and the diagnosis is based on clinical, biochemical and genetic criteria. We report 2 siblings with Donohue syndrome (cases 1, 2) with multiple clinical and biochemical characteristics. Both patients shared the same mutation and presented with intra-uterine growth restriction, failure to thrive, fasting hyperinsulinaemic hypoglycaemia and episodic post-prandial hyperglycaemia. Less common clinical features were also present, such as atrial septal defect and biventricular hypertrophy, clotting disorders, abnormal liver function tests and nephrocalcinosis. Interestingly, 2 previously unrecognized manifestations of the syndrome were also identified: severe gastrointestinal dysmotility (case 1) and exocrine pancreatic insufficiency (case 2). The co-existence of all the above clinical features makes these cases extremely rare. Gastrointestinal dysmotility should always be considered as a potentially fatal feature in patients with the syndrome, due to the complexity of the possible co-morbidities. In addition, our clinical experience for the first time suggests that pancreatic exocrine insufficiency may offer a possible explanation for the growth retardation observed in some patients with this syndrome. Our finding that replacement treatment with pancreatic enzymes improved weight gain (case 2) implies that all patients with Donohue syndrome should be investigated for exocrine pancreatic insufficiency. [ABSTRACT FROM AUTHOR]

Background There is interest in ultimately combining endoscopy and motility assessments. Gastric emptying ( GET), small bowel ( SBTT), colon ( CTT) and whole gut transit ( WGTT) times are conveniently obtained by SmartPill® wireless motility capsule ( WMC) that records luminal pH, temperature and pressure. Reproducibility within same subjects and accuracy of software derived times (Motili GI®) were investigated for diagnostic application. GET and SBTT were separately measured using video capsule endoscopy ( VCE). The aim of this investigation was to assess same subject reproducibility of WMC, accuracy of software derived transit times and relate to Pillcam® SB (small bowel) VCE motility data. Methods Seventy three healthy adults ingested a 260 kcal mixed meal followed by WMC tests. Food intake was permitted after 6 hours. Regional transit data was obtained for GET, SBTT and CTT, the sum yielding WGTT. Nineteen subjects repeated WMC tests 2 or 4 weeks later; a separate 70 underwent VCE while fasted. Key Results Visually derived data from WMC yielded GET 3.46±0.27, SBTT 5.15±0.21, CTT 20.76±1.19 and WGTT 29.53±1.28 hours (mean± SEM). Pearson's correlation coefficients ( r) against software derived results were: GET 0.78 ( P<.0001), SBTT 0.28 ( P<.05), CTT 0.96 ( P<.0001), WGTT 0.99 ( P<.0001). VCE yielded lower GET (0.71±0.08 hours) and SBTT (4.15±0.13 hours). Conclusions and Inferences GET, SBTT, CTT and WGTT obtained by WMC are commensurate with literature values, including by other methods. Visually and software derived transit times have strongest correlations for CTT and WGTT. WMC yields longer GET and SBTT than VCE, perhaps due to meal related effects on motility. [ABSTRACT FROM AUTHOR]