Tenapanor in the Treatment of Irritable Bowel Syndrome with Constipation: Discovery, Efficacy, and Role in Management.

Irritable bowel syndrome (IBS) is a common disorder of gut-brain interaction (DGBI). IBS significantly impacts the quality of life of patients. Since its pathogenesis is unclear and can be multifactorial, it highlights the need for new and improved pharmaceutical drugs that not only improve bowel symptoms, but also address global IBS symptoms, such as abdominal pain. Tenapanor, a recently Food & Drug Administration (FDA)-approved medication for IBS with constipation (IBS-C), is a small molecule inhibitor of the sodium/hydrogen exchanger isoform 3 (NHE3) that inhibits the absorption of sodium and phosphate in the gastrointestinal tract, resulting in fluid retention and softer stool. Furthermore, tenapanor reduces intestinal permeability to improve visceral hypersensitivity and abdominal pain. Due to its recent approval, tenapanor was not included in the recent IBS guidelines, however, it may be considered for IBS-C patients failing first-line treatment of soluble fiber. In this review article, we aim to provide in-depth information to the reader regarding the design of tenapanor, its development through Phase I, II and III randomized clinical trials, and its role in the treatment of IBS-C.

Characterizing reflux on high resolution esophageal manometry with impedance.

BACKGROUND: In some patients, reflux at esophagogastric junction (EGJ) can be seen on the impedance portion of the high-resolution esophageal manometry with impedance (HREMI) studies. How this correlates with reflux on conventional esophageal reflux monitoring studies is unknown. We aimed to: (1) determine prevalence of reflux seen on HREMI, (2) correlate reflux during HREMI with reflux on esophageal reflux monitoring studies. METHODS: Patients undergoing HREMI and ambulatory reflux monitoring (7/2019 to 2/2020) were studied. Healthy volunteers (HVs) underwent HREMI. KEY RESULTS: Sixteen HVs underwent HREMI (no reflux on HREMI = 13, reflux on 1 swallow on HREMI = 3). Of 229 patients (mean age 56.4 ± 1.0, 68.1% females) undergoing HREMI, 47 (20.5%) had pathologic reflux at EGJ on HREMI (reflux on ≥ 2 swallows). The patients with reflux on HREMI had more frequent reflux events on multichannel intraluminal impedance-pH (MII-pH) than patients without reflux on HREMI (63.5 ± 7.1 vs 42.1 ± 2.3, p = 0.01). On ambulatory pH monitoring, 113 (49.3%) had GERD and 42 (18.3%) borderline results. Patients with reflux on HREMI more commonly had GERD (56.3% vs 48.6%) and borderline results (28.1% vs 18.3%) than patients without reflux on HREMI (p = 0.01). Reflux on ≥ 2 swallows on HREMI had a specificity of 83.6% and sensitivity of 24.8% for GERD. Reflux on ≥ 5 swallows on HREMI improved specificity to 91.4%, with sensitivity of 14.2% for GERD. CONCLUSIONS AND INFERENCES: Amongst patients undergoing HREMI, 20.5% had pathologic reflux at EGJ on HREMI. Patients with reflux on HREMI more frequently had GERD on ambulatory pH monitoring. Reflux on HREMI had good specificity but low sensitivity for GERD.

A Retrospective Study of Hospitalizations in the USA: Proportion of Hospitalizations With Non-Alcoholic Fatty Liver Disease in Non-Obese Population.

Background Non-alcoholic fatty liver disease (NAFLD), one of the leading causes of end-stage liver disease, is known to be associated with obesity. However, only a few studies in the United States (US) have described non-obese NAFLD, most of which were on the outpatient population. Aim We aimed to investigate the proportion of hospitalizations in the US with a diagnosis code that included NAFLD in the non-obese population. Methods We analyzed adult discharges from the Nationwide Inpatient Sample with a diagnosis of NAFLD from January 2010 to December 2014. We created two groups: obese (overweight or obese) and non-obese (normal or underweight) groups. Basic demographic and clinical characteristics were compared using the chi-square test and Student's t-test. Results A total of 194,787 hospitalizations with NAFLD were identified over the five-year period. It was observed that the prevalence of non-obese NAFLD hospitalizations increased yearly. Non-obese NAFLD hospitalizations had a higher mean age (57.5 vs 51.5 years, p < 0.0001) and a higher proportion of males (43.3% vs 36.1%, p < 0.0001) than obese NAFLD hospitalizations. With univariate analysis, non-obese NAFLD hospitalizations had lower odds of hypertension (OR 0.74, p < 0.0001), diabetes mellitus (OR 0.65, p < 0.0001). Non-obese hospitalizations had higher odds of cirrhosis (OR 1.30, p < 0.001) and decompensated cirrhosis (OR 1.30, p < 0.001) after adjusting for age, sex, race, diabetes mellitus, and dyslipidemia. Hospitalizations with non-obese NAFLD had higher odds of death (OR 1.49, p < 0.001) after adjusting for age, gender, race, co-morbidities, cirrhosis, and liver decompensation. Conclusion There is a continued rise in the proportion of non-obese NAFLD among hospitalizations in the US. Non-obese NAFLD hospitalizations were less likely to have hypertension and diabetes, but more likely to have decompensated liver disease. Further studies are needed to better characterize these patients to enable early detection, treatment, and reduction in complications of liver disease.

Prevalence and Clinical Characteristics of Dyssynergic Defecation and Slow Transit Constipation in Patients with Chronic Constipation.

Patients with chronic constipation who do not respond to initial treatments often need further evaluation for dyssynergic defecation (DD) and slow transit constipation (STC). The aims of this study are to characterize the prevalence of DD and STC in patients referred to a motility center with chronic constipation and correlate diagnoses of DD and STC to patient demographics, medical history, and symptoms. High-resolution ARM (HR-ARM), balloon expulsion testing (BET) and whole gut transit scintigraphy (WGTS) of consecutive patients with chronic constipation were reviewed. Patients completed questionnaires describing their medical history and symptoms at the time of testing. A total of 230 patients completed HR-ARM, BET, and WGTS. Fifty (22%) patients had DD, and 127 (55%) patients had STC. Thirty patients (13%) had both DD and STC. There were no symptoms that were suggestive of STC vs. DD; however, patients with STC and DD reported more severe constipation than patients with normal transit and anorectal function. Patients with chronic constipation often need evaluation for both DD and STC to better understand their pathophysiology of symptoms and help direct treatment.

Haloperidol Use in the Emergency Department for Gastrointestinal Symptoms: Nausea, Vomiting, and Abdominal Pain.

INTRODUCTION: Haloperidol (HL) has successfully been used for nausea and abdominal pain in emergency departments (EDs). This study examines outcomes and predictive factors for clinical improvement of patients presenting to an ED with gastrointestinal (GI) symptoms (nausea, vomiting, and abdominal pain) who received HL. METHODS: Review of patients' records who presented to our ED between August 2016 and March 2019 with GI symptoms and received HL. International Classification of Diseases, Tenth Revision codes were used to identify patients. RESULTS: In all, 281 patients (410 encounters) presented to the ED with GI symptoms and received HL for their symptoms: 66% were women, 32% had diabetes, 68% used marijuana, and 27% used chronic opioids. Patients received HL 1.1 ± 0.3 times with dose 2.5 ± 3.0 mg, mostly intravenously (84.6%). Total ED length of stay was 7.5 ± 3.9 hours (3.2 ± 2.1 hours before HL and 4.4 ± 3.4 hours after). Approximately 4.4% of patients developed side effects to HL, including 2 patients with dystonia which improved with medication before discharge. Most patients (56.6%) were discharged home while 43.2% were admitted to hospital mostly because of refractory nausea or vomiting (70.1%). Receiving HL as the only medication in the ED led to lower hospital admission (odds ratio = 0.25, P < 0.05). Diabetes, cannabinoid use, anxiety, male sex, and longer ED stay were associated with increased hospital admissions. DISCUSSION: Most patients treated in our ED with HL for GI symptoms, particularly nausea, vomiting, and/or abdominal pain, were successfully treated and discharged home. HL use seemed relatively safe and, when used as the only medication, led to less frequent hospital admissions.

Detection and characteristics of rumination syndrome in patients presenting for gastric symptom evaluation.

BACKGROUND: Rumination syndrome involves effortless, repeated regurgitation, and can overlap with other upper gastrointestinal disorders, including gastroparesis. To inform better diagnostic detection of rumination, we aimed to (1) identify frequency and characteristics of rumination in patients presenting for gastric symptom evaluation; and (2) assess demographic and clinical characteristics that could differentiate those with versus those without rumination. METHODS: Consecutively referred patients to two tertiary academic centers for gastric symptom specialty evaluation were included (N = 242). We obtained demographic information, gastric emptying scintigraphy, upper gastrointestinal symptoms using the Patient Assessment of Upper Gastrointestinal Symptoms (PAGI-SYM), and Rome IV-based rumination questionnaire. KEY RESULTS: Thirty-one of the 242 (12.8%) patients met criteria for rumination syndrome, of which 48% reported associated psychosocial impairment. Comparing those with rumination and those without, there were no differences in race, gender, frequency of diabetes, or frequency of gastroparesis. The median PAGI-SYM score for rumination patients was higher than for those without (3.03 vs. 2.55; unadjusted p = 0.043, adjusted p = 0.30). This was largely driven by increased heartburn/regurgitation subscale scores (2.71 vs. 1.57, unadjusted p = 0.0067, adjusted p = 0.046), itself influenced by elevated daytime regurgitation/reflux (3.0 vs. 2.0; unadjusted p = 0.007, adjusted p = 0.048). There were no significant differences on the remaining PAGI-SYM subscales. CONCLUSIONS AND INFERENCES: Rumination syndrome determined by Rome IV criteria was present in 12.8% of patients presenting for gastric symptom evaluation. Higher self-report PAGI-SYM heartburn/regurgitation subscale scores, particularly daytime regurgitation/reflux symptoms, were the only parameters that distinguished rumination. The PAGI-SYM heartburn/regurgitation subscale could be used to screen for rumination, in addition to GERDAQ6.

Rheumatologic disorders in patients undergoing esophageal manometry: prevalence, symptom characteristics, and manometric findings.

Rheumatologic disorders (RDs) can have gastrointestinal (GI) manifestations. Systemic sclerosis (SSc) patients often have upper GI symptoms from absent esophageal contractility (AC). Upper GI symptom characteristics and high-resolution esophageal manometry with impedance (HREMI) findings of other RDs have not been well studied. We aimed to: (i) determine the prevalence of RD in patients undergoing HREMI and (ii) assess the symptom characteristics and manometric findings of these patients. Patients undergoing HREMI (July 2018 to March 2020) rated their GI symptoms' severity. Healthy volunteers (HVs) also underwent HREMI. Of the 1,003 patients, 90 (9%) had RD (mean age: 55.3 ± 1.4 years, 73.3% females), most commonly SSc (n = 27), rheumatoid arthritis (RA, n = 20), and systemic lupus erythematosus (SLE, n = 11). The most severe upper GI symptoms in patients with RD were heartburn, regurgitation, nausea, and dysphagia, with no significant differences in their severities between SSc, RA, and SLE. RD patients had higher upper esophageal sphincter (UES) pressures, lower distal contractile integral (DCI), lower bolus clearance, and more frequent hiatal hernia (HH) on HREMI (all P < 0.05) than HVs. Over half (61.1%) of patients with RD had esophageal motility disorders, most commonly AC (n = 25), ineffective esophageal motility (IEM; n = 18), and esophagogastric junction (EGJ) obstructive disorders (n = 11). Among patients undergoing HREMI, 9% had RD. Upper GI symptom severities did not distinguish different RDs. Patients with RD had higher UES pressures, weaker DCI, lower bolus clearance, and more frequent HH than HVs. Although AC and IEM were most common motility disorders, a considerable minority (12.2%) of our RD patients had EGJ obstructive disorders.

EndoFLIP and Pyloric Dilation for Gastroparesis Symptoms Refractory to Pyloromyotomy/Pyloroplasty.

BACKGROUND: Gastroparesis patients may undergo pyloromyotomy/pyloroplasty for chronic refractory symptoms. However, some patients have persistent symptoms. It is unknown if balloon dilation may improve their symptoms. AIMS: We aimed to (1) assess if pyloric through-the-scope (TTS) balloon dilation results in symptom improvement in gastroparesis patients with suboptimal response to pyloromyotomy/pyloroplasty and (2) determine endoscopic functional luminal imaging probe (EndoFLIP) characteristics of these patients before dilation. METHODS: Patients with severe gastroparesis refractory to pyloromyotomy/pyloroplasty seen from 2/2019 to 3/2020 underwent pyloric TTS dilation after assessing the pyloric characteristics using EndoFLIP. Patients completed Gastroparesis Cardinal Symptom Index (GCSI) pre-procedurally, and GCSI and Clinical Patient Grading Assessment Scale (CPGAS) on follow-ups. RESULTS: Thirteen (ten females) patients (mean age 45.2 ± 5.1 years) with severe gastroparesis symptoms (mean GCSI total score 3.4 ± 0.3) after pyloromyotomy/pyloroplasty underwent pyloric TTS dilation. Overall, there was improvement in symptoms at 1-month follow-up (mean GCSI total score 3.0 ± 0.4, mean CPGAS score 1.6 ± 0.5, p < 0.05 for both), with five (38%) patients reporting symptoms somewhat/moderately better. The patients with symptom improvement had lower pre-dilation pyloric EndoFLIP distensibility at 30 ml, 40 ml, and 50 ml than patients with little/no improvement (all p < 0.05). CONCLUSIONS: In gastroparesis patients with refractory symptoms after pyloromyotomy/pyloroplasty, pyloric TTS dilation improved symptoms in about a third of the patients. Patients with symptom improvement had lower pre-dilation pyloric distensibility on EndoFLIP suggesting incomplete myotomy, pyloric muscle regeneration, or pyloric stricture. Pyloric EndoFLIP followed by TTS dilation seems to be a promising treatment for some patients with gastroparesis symptoms refractory to pyloromyotomy/pyloroplasty.

Dieulafoy lesion in the jejunum: a rare cause of massive gastrointestinal bleeding.

Dieulafoy lesions are tortuous vascular malformations characterized by thick walled submucosal arteries/large caliber arterioles protruding through a small mucosal defect surrounded by normal mucosa. They can occur in the jejunum/ileum and can cause massive, life-threatening GI bleeding. We present an 80-year-old female with three weeks of black tarry stools, progressive dyspnea on exertion and generalized body weakness with no significant findings on Esophagogastroduodenoscopy (EGD). Push enteroscopy revealed a Dieulafoy lesion in the proximal jejunum and an overlying clot, with oozing of blood noted after clot removal. The lesion was treated with Argon plasma coagulation (APC) and a post-APC fleshy protuberance was clipped to secure hemostasis. It is therefore important to keep a high index of suspicion for jejunal/ileal Dieulafoy lesions in patients with massive GI bleeding of unclear etiology on EGD/colonoscopy.

Avoidant/restrictive food intake disorder symptoms are frequent in patients presenting for symptoms of gastroparesis.

INTRODUCTION: Patients with symptoms of gastroparesis/dyspepsia often avoid foods or restrict eating for symptom management. There is growing interest in understanding risk for feeding/eating disorders (FEDs) like avoidant/restrictive food intake disorder (ARFID). Among patients presenting with gastroparesis/dyspepsia symptoms, we aimed to determine: (a) FED symptom frequency, and (b) relation of FED symptoms to gastrointestinal symptom severity and gastric retention abnormalities. METHODS: Adult patients (N = 288; 78% female) referred for gastroparesis/dyspepsia symptoms at two academic medical centers from January 2018-February 2019 completed self-report surveys for gastrointestinal symptom severity and FED symptoms. Gastric retention data were available for 210 patients, using 4-hour EggBeater gastric emptying scintigraphy (GES). RESULTS: Clinically significant FED symptoms were present in 158 patients (54.9%). Interestingly, 115 patients (39.9%) met conservative self-report cutoff for ARFID symptoms, with 67 (23.3%) patients having documented psychosocial/medical impairment. Of those with survey data for other FEDs (n = 239), only 28 patients (11.7%) had restrictive eating disorders (anorexia nervosa; unspecified FED). Likelihood of having FED symptoms was significantly associated with greater gastroparesis symptom severity (OR = 2.23, P < .001), but not GES. In addition, gastroparesis symptom severity was moderately and significantly associated with greater ARFID symptom severity (b = 0.45, P < .001), but neither GES nor other FED symptoms. DISCUSSION: In patients presenting with gastroparesis/dyspepsia symptoms, FED symptoms were frequent (55%), particularly ARFID, and were associated with greater gastrointestinal symptom severity, but not gastric retention. Gastroparesis/dyspepsia symptoms may mimic FEDs, particularly ARFID. Clinicians should be cautious about diagnosing ARFID in gastroparesis/dyspepsia patients, and screening for ARFID could assist behavioral treatment referral.

Characterizing the proximal esophageal segment in patients with symptoms of esophageal dysmotility.

BACKGROUND: Proximal esophageal striated muscle contractility may be abnormal in patients with esophageal symptoms, but is not assessed in the Chicago Classification (CC) v3.0. We aimed to (a) determine the prevalence of abnormal proximal esophageal contractility in patients with esophageal symptoms; (b) compare proximal esophageal contractility in patients with different esophageal motility disorders; (c) assess the association of abnormal proximal esophageal contractility with esophageal symptoms. METHODS: Patients undergoing high-resolution esophageal manometry (HREM) from 7/2019 to 11/2019 and healthy volunteers (HVs) were studied. Measurements of the proximal esophageal segment included the vigor of contractility of the proximal esophagus (proximal contractile integral/PCI). Patients rated gastrointestinal symptoms' severity. KEY RESULTS: HREM was performed on 221 patients (63.8% females, mean age 57.1 ± 1.1 years) and 19 HVs. Mean PCI in HVs was 299.5 ± 30.6 (95% CI 32.3-566.7 mm Hg. s. cm). Of all patients, 61 (27.6%) had abnormal PCI. HVs and patients with different esophageal motility disorders had significantly different PCI (P < .01). Type 1 achalasia patients had weaker PCI than patients with absent contractility (P = .02). Patients with abnormal PCI had more severe dysphagia (P = .02), nausea (P = .03), vomiting (P = .03), and lower bolus clearance (P < .01) than patients with normal PCI. CONCLUSIONS AND INFERENCES: Abnormal PCI was found in a fourth of patients with esophageal symptoms. PCI may be useful to distinguish some esophageal motility disorders. Patients with abnormal PCI had a higher severity of some upper gastrointestinal symptoms than patients with normal PCI. Assessing the proximal esophageal segment on HREM may be useful in characterizing patients with esophageal symptoms.

Reflux Symptoms in Gastroparesis: Correlation With Gastroparesis Symptoms, Gastric Emptying, and Esophageal Function Testing.

GOAL: The goal of this study was to determine the relationship of reflux with gastroparesis (Gp), looking both at symptoms and objective testing. BACKGROUND: Gp patients often experience gastroesophageal reflux symptoms. How the severity of reflux correlates with the severity of Gp is not known. STUDY: Patients referred to our academic center with symptoms of Gp completed the Patient Assessment of Upper Gastrointestinal Symptoms, Hospital Anxiety and Depression Scale, and Patient Health Questionnaire (PHQ)-15. They underwent 4-hour gastric emptying scintigraphy; and, if indicated, high-resolution esophageal manometry and esophageal pH impedance (EpHI). RESULTS: Of 755 patients from July 2013 to May 2018, 432 had Gp with Gastroparesis Cardinal Symptom Index (GCSI) total score of 3.2±0.1 (mean±SEM) and heartburn/regurgitation subscore of 2.0±0.1. A fourth (27.1%) of all Gp patients had moderate to very severe heartburn/regurgitation symptoms. Heartburn/regurgitation subscore had strong correlation with GSCI total score (r=0.56, P<0.01), and weak correlation with 4-hour gastric retention (r=0.11, P=0.02). In total, 103 Gp patients underwent EpHI monitoring; time esophageal pH<4 had no correlation with heartburn/regurgitation subscore. Less than half (41.7%) of the patients undergoing EpHI had gastroesophageal reflux disease by EpHI. Gp patients with gastroesophageal reflux disease had more severe 4-hour gastric retention, and more frequently had decreased lower esophageal sphincter resting pressure and esophageal motility disorders. Heartburn/regurgitation subscore had moderate correlation with somatic symptoms, and weak correlations with anxiety and depression. CONCLUSIONS: The severity of reflux symptoms in Gp has strong correlation with GCSI total score, weak correlation with gastric retention, and no correlation with esophageal pH monitoring.

Surgical Treatment for Refractory Gastroparesis: Stimulator, Pyloric Surgery, or Both?

BACKGROUND: Several surgical options exist for refractory gastroparesis (Gp) including gastric electric stimulation (GES) and pyloric surgery (PS) such as pyloromyotomy or pyloroplasty. Few studies exist comparing the outcomes of these surgeries. AIM: Compare the clinical outcomes of GES, PS, and simultaneous GES+PS for refractory Gp. METHODS: Patients undergoing surgical intervention at our medical center from January 2016 to April 2019 were given pre- and post-surgery questionnaires to assess their response to intervention: Patient Assessment of Upper Gastrointestinal Symptoms (PAGI-SYM) grading symptoms and Clinical Patient Grading Assessment Scale (CPGAS) grading response to treatment. Results are expressed as mean ± SE. RESULTS: One hundred thirty-two patients underwent surgical intervention; 12 were excluded. Mean CPGAS improvement overall was 2.8 ± 0.2 (p < 0.01): GES+PS had CPGAS score at 3.6 ± 0.5, pyloric interventions 3.1 ± 0.5, and GES 2.5 ± 0.4 (p > 0.05). Mean improvement in Gastroparesis Cardinal Symptom Index (GCSI) total score was 1.0 ± 0.1 (p < 0.01), with improvement of 1.1 ± 0.2 for GES + PS, 0.9 ± 0.2 for GES, and 0.9 ± 0.2 for PS (p > 0.05). GES and GES + PS, but not PS only, significantly improved symptoms of nausea and vomiting (p < 0.01). Among gastroparesis subtypes, patients with diabetic gastroparesis had more improvement on nausea/vomiting subscale compared with idiopathic gastroparesis (p = 0.028). CONCLUSIONS: Patients with refractory symptoms of Gp undergoing GES, PS, or combined GES+PS each had significant improvement of their GCSI total score. GES and combined GES+PS significantly improved nausea/vomiting. These results suggest GES or combined GES+PS appears better for nausea/vomiting predominant refractory Gp.

Symptom variability throughout the day in patients with gastroparesis.

BACKGROUND: Symptoms of gastroparesis (Gp) can fluctuate at different times of the day. Our aims are (1) To characterize Gp symptom variability throughout the day and in relation to meals and (2) to compare the daily symptom variability in subtypes of Gp-diabetic gastroparesis (DGp) and idiopathic gastroparesis (IGp). METHODS: Patients with Gp filled Patient Assessment of Gastrointestinal Symptoms (PAGI-SYM) and completed a modified GCSI-DD seven times a day (GCSI-Throughout the Day [GCSI-TTD]; before and after meals, and before going to bed) over a 2-week period. KEY RESULTS: A total of 44 patients participated (86% females), including 29 (66%) with IGp, 13 (30%) with DGp, and 2 (4%) with postsurgical Gp. Using the GCSI-TTD, patients with Gp reported significant postprandial worsening of overall symptom severity, as well as severities of nausea, early satiety, stomach fullness, and abdominal pain. Patients also had progressive worsening of the overall symptom severity, early satiety, stomach fullness, and abdominal pain during the day; however, nausea severity did not differ during the day. Number of vomiting and retching episodes did not show significant variations postprandially or during the day. Patients with IGp had greater symptom severity throughout the day and greater postprandial increase in symptoms compared to patients with DGp. CONCLUSIONS AND INFERENCES: Patients with Gp experience postprandial worsening of overall symptom severity, as well as severities of nausea, early satiety, stomach fullness, and abdominal pain. These symptoms also progressively worsen during the day, except for the severity of nausea which persists throughout the day. Understanding the symptom variability in patients with Gp throughout the day and postprandially may be useful in treatment of patients with Gp.

Acute vascular insufficiency of intestine: incidence highest in summer, outcomes worst in winter.

BACKGROUND: The incidence of acute vascular insufficiency of intestine (AVII) is on the rise in the USA and is associated with significant morbidity and mortality. Seasonal variations have been observed in the onset of several gastrointestinal diseases. It is thus far unknown whether the incidence, in-hospital mortality rates, and length of hospital stay (LOS) of AVII vary in different seasons. AIMS: The aims of this study were to study the seasonal variations in the (1) incidence, (2) in-hospital mortality, and (3) LOS of AVII in the USA. METHODS: We used the Nationwide Inpatient Sample to identify patients aged ≥ 18 years hospitalized from the years 2000-2014. We used the Edwards recognition with estimation of cyclic trend method to study the seasonal variation of AVII hospitalizations and z test to compare the seasonal incidences (peak-to-low ratio), mortalities, and LOS. RESULTS: A total of 1,441,447 patients were hospitalized with AVII (0.3% of all hospitalizations). Patients with AVII were older (69.0 ± 0.1 vs 56.9 ± 0.1) and more commonly females (65.4% vs 35.5%) than patients without AVII (p < 0.001). The incidence of AVII increased through the summer to peak in September (peak/low ratio 1.028, 95% CI 1.024-1.033, p < 0.001). Patients with AVII hospitalized in winter had the highest mortality (17.3%, p < 0.001) and LOS (9.2 ± 0.7 days, p < 0.001). CONCLUSIONS: The incidence of AVII in the USA peaks in late summer. The in-hospital mortality rates and LOS associated with AVII are the highest in winter. Physicians could be cognizant of the seasonal variations in the incidence, in-hospital mortality, and LOS of AVII.

Gastric Electric Stimulation for Refractory Gastroparesis.

OBJECTIVE: To outline the use and utility of gastric electric stimulation (GES) as a therapeutic intervention for gastroparesis. METHODS: Review of the literature. RESULTS: Gastroparesis is characterized by delayed gastric emptying, with symptoms of nausea, vomiting, early satiety, postprandial fullness, and abdominal pain. Some patients with gastroparesis do not respond to medical intervention, and for these patients surgical intervention may be warranted. GES utilizes high-frequency gastric neurostimulation to facilitate gastric emptying and reduce symptoms of gastroparesis. It is indicated for patients with idiopathic and diabetic gastroparesis who have nausea and vomiting as their primary symptoms and who have not responded to medical therapy. GES has also been used in postsurgical and pediatric gastroparesis patients. Optimizing the outcome of this surgical treatment through proper patient selection and meticulous surgical technique is essential as there are inherent risks to the procedure. Nonblinded studies of GES for medically refractory gastroparesis have demonstrated therapeutic symptomatic benefit, whereas randomized controlled trials have not. New interventions such as pyloromyotomy and pyloroplasty are reasonable alternatives or addendums to GES. CONCLUSION: GES may be considered among the therapies available for treating patients with refractory symptoms of gastroparesis. More studies, specifically those comparing GES, pyloromyotomy, GES combined with pyloromyotomy, and placebo, are needed to help guide therapy selection for refractory gastroparesis.

Metoclopramide for the treatment of diabetic gastroparesis.

Introduction: Gastroparesis is a chronic disorder of the stomach characterized by delayed gastric emptying without mechanical obstruction. Diabetes is the most commonly known cause of gastroparesis. Management of diabetic gastroparesis involves lifestyle modifications, glycemic control, pharmacological drugs, and for refractory cases surgical treatments. Metoclopramide remains the only drug approved by the Food and Drug Administration for diabetic gastroparesis. The aim of this article is to provide a concise review of the pharmacology, clinical efficacy and tolerability of metoclopramide. Areas covered: We searched PubMed using the key words 'metoclopramide', 'diabetic gastroparesis', and 'gastric emptying'. The relevant articles and their bibliography were reviewed. Metoclopramide acts on several different receptors; primarily as a dopamine receptor antagonist, both peripherally improving gastric emptying, and centrally resulting in an anti-emetic effect. Metoclopramide side effects, mostly related to its ability to cross the blood-brain barrier, include drowsiness, restlessness, hyperprolactinemia, and tardive dyskinesia (TD), a movement disorder that may be irreversible. Expert opinion: Metoclopramide carries a black box warning for use >12 weeks due to the risk of TD. However, gastroparesis patients experience chronic symptoms often requiring prolonged treatments. Physicians and patients look forward to FDA approval of new agents for gastroparesis with better efficacy and safety profile.

Caregiver Burden in Gastroparesis and GERD: Correlation with Disease Severity, Healthcare Utilization and Work Productivity.

BACKGROUND: Caregiver burden can be significant in chronic gastrointestinal diseases. No studies have been performed to evaluate caregiver burden in gastroparesis or gastroesophageal reflux disease (GERD). AIMS: (1) Assess the caregiver burden in gastroparesis and GERD patients and healthy volunteers (HVs); (2) correlate the caregiver burden of these patients to the severity of patients' symptoms, healthcare utilization, and work productivity of the patients and the caregivers. METHODS: Patients with gastroparesis and GERD, seen between June 2018 and November 2018, completed Patient Assessment of Gastrointestinal Symptoms, Work Productivity and Activity Impairment (WPAI) and healthcare utilization questionnaires. The caregivers of these patients completed Zarit Burden Interview (ZBI) and WPAI questionnaire. HVs and their potential caregivers also completed these questionnaires. RESULTS: Forty-seven patients (gastroparesis = 31, GERD = 17), 12 HVs, and their caregivers completed questionnaires. Caregivers of gastroparesis patients reported high burden on ZBI (27.7 ± 2.9), greater than the caregivers of GERD (14.9 ± 2.5) and HVs (5.5 ± 1.6, p < 0.01). Among all patients, the caregiver burden had a strong correlation with patients' Gastroparesis Cardinal Symptom Index (GCSI) total score (rs = 0.63, p < 0.01) and moderate correlations with the number of patients' physician office visits (rs = 0.46, p < 0.01) and the number of work hours missed by caregivers due to patients' symptoms (rs = 0.36, p = 0.04). Using multivariable regression, both presence of gastroparesis and other comorbidities significantly predicted caregiver burden, F(2, 33) = 15.94, p < 0.0001, R2 = 0.491. CONCLUSIONS: Caregivers of gastroparesis patients have high caregiver burden that strongly correlates with patients' GCSI total score. Interventions to reduce symptom severity of Gp patients may reduce the caregiver burden.