Intestinal Permeability, Irritable Bowel Syndrome with Constipation, and the Role of Sodium-Hydrogen Exchanger Isoform 3 (NHE3).

Increased intestinal permeability has been identified as one of the many pathophysiological factors associated with the development of irritable bowel syndrome (IBS), a common disorder of gut-brain interaction. The layer of epithelial cells that lines the intestine is permeable to a limited degree, and the amount of paracellular permeability is tightly controlled to enable the absorption of ions, nutrients, and water from the lumen. Increased intestinal permeability to macromolecules can be triggered by a variety of insults, including infections, toxins from food poisoning, or allergens, which in turn cause an inflammatory response and are associated with abdominal pain in patients with IBS. This review article discusses increased intestinal permeability in IBS, focusing on IBS with constipation (IBS-C) through the lens of a patient case with a reported prior diagnosis of "leaky gut syndrome" upon initial contact with a gastrointestinal specialist. We review advantages and disadvantages of several methods of measuring intestinal permeability in patients and discuss when measuring intestinal permeability is appropriate in the therapeutic journey of patients with IBS-C. Furthermore, we discuss a possible mechanism of restoring the intestinal barrier to its healthy state through altering intracellular pH by inhibiting sodium-hydrogen exchanger isoform 3 (NHE3). Tenapanor is a minimally absorbed, small-molecule inhibitor of NHE3 that has been approved by the US Food and Drug Administration for the treatment of IBS-C in adults. Preclinical studies showed that tenapanor may restore the intestinal barrier in IBS-C by affecting the conformation of tight junction proteins via NHE3 inhibition to block the paracellular transport of macromolecules from the intestinal lumen. Testing for increased permeability in patients with IBS-C who experience abdominal pain may help inform the choice of therapeutics and alter patients' misconceptions about "leaky gut syndrome".

A Multidisciplinary Assessment of ChatGPT's Knowledge of Amyloidosis: Observational Study.

BACKGROUND: Amyloidosis, a rare multisystem condition, often requires complex, multidisciplinary care. Its low prevalence underscores the importance of efforts to ensure the availability of high-quality patient education materials for better outcomes. ChatGPT (OpenAI) is a large language model powered by artificial intelligence that offers a potential avenue for disseminating accurate, reliable, and accessible educational resources for both patients and providers. Its user-friendly interface, engaging conversational responses, and the capability for users to ask follow-up questions make it a promising future tool in delivering accurate and tailored information to patients. OBJECTIVE: We performed a multidisciplinary assessment of the accuracy, reproducibility, and readability of ChatGPT in answering questions related to amyloidosis. METHODS: In total, 98 amyloidosis questions related to cardiology, gastroenterology, and neurology were curated from medical societies, institutions, and amyloidosis Facebook support groups and inputted into ChatGPT-3.5 and ChatGPT-4. Cardiology- and gastroenterology-related responses were independently graded by a board-certified cardiologist and gastroenterologist, respectively, who specialize in amyloidosis. These 2 reviewers (RG and DCK) also graded general questions for which disagreements were resolved with discussion. Neurology-related responses were graded by a board-certified neurologist (AAH) who specializes in amyloidosis. Reviewers used the following grading scale: (1) comprehensive, (2) correct but inadequate, (3) some correct and some incorrect, and (4) completely incorrect. Questions were stratified by categories for further analysis. Reproducibility was assessed by inputting each question twice into each model. The readability of ChatGPT-4 responses was also evaluated using the Textstat library in Python (Python Software Foundation) and the Textstat readability package in R software (R Foundation for Statistical Computing). RESULTS: ChatGPT-4 (n=98) provided 93 (95%) responses with accurate information, and 82 (84%) were comprehensive. ChatGPT-3.5 (n=83) provided 74 (89%) responses with accurate information, and 66 (79%) were comprehensive. When examined by question category, ChatGTP-4 and ChatGPT-3.5 provided 53 (95%) and 48 (86%) comprehensive responses, respectively, to "general questions" (n=56). When examined by subject, ChatGPT-4 and ChatGPT-3.5 performed best in response to cardiology questions (n=12) with both models producing 10 (83%) comprehensive responses. For gastroenterology (n=15), ChatGPT-4 received comprehensive grades for 9 (60%) responses, and ChatGPT-3.5 provided 8 (53%) responses. Overall, 96 of 98 (98%) responses for ChatGPT-4 and 73 of 83 (88%) for ChatGPT-3.5 were reproducible. The readability of ChatGPT-4's responses ranged from 10th to beyond graduate US grade levels with an average of 15.5 (SD 1.9). CONCLUSIONS: Large language models are a promising tool for accurate and reliable health information for patients living with amyloidosis. However, ChatGPT's responses exceeded the American Medical Association's recommended fifth- to sixth-grade reading level. Future studies focusing on improving response accuracy and readability are warranted. Prior to widespread implementation, the technology's limitations and ethical implications must be further explored to ensure patient safety and equitable implementation.

Exploring the aperiodic nature of parasympathetic activity during sleep in idiopathic gastroparesis.

The parasympathetic nervous system is necessary to regulate both sleep and digestion. Investigating abnormalities during the controlled setting of sleep can shed light on digestion, specifically for patients with idiopathic gastroparesis. In this study, we specifically investigate heartbeat-derived parasympathetic activity during sleep at very low frequencies, relevant to sleep cycle regulation. To do this, we adapt a method that extracts both periodic and aperiodic information from the power spectral density and recognize that the aperiodic activity may contain information relevant to very low frequencies. After testing on both synthetic noise data (pink and white) and overnight data from seven healthy controls and idiopathic gastroparetics, we find that the healthy controls' low-frequency aperiodic activity reflects pink noise structure, while the majority of the patients' aperiodic activity reflects white noise structure. At these low frequencies, these differences suggest differences in autonomic sleep cycle regulation.Clinical Relevance- This methodology can be optimized to track the health of the parasympathetic nervous system and suggest whether individual disease etiology is autonomic-related.

Optimizing the Utility of Anorectal Manometry for Diagnosis and Therapy: A Roundtable Review and Recommendations.

BACKGROUND & AIMS: Anorectal manometry (ARM) is a comprehensive diagnostic tool for evaluating patients with constipation, fecal incontinence, or anorectal pain; however, it is not widely utilized for reasons that remain unclear. The aim of this roundtable discussion was to critically examine the current clinical practices of ARM and biofeedback therapy by physicians and surgeons in both academic and community settings. METHODS: Leaders in medical and surgical gastroenterology and physical therapy with interest in anorectal disorders were surveyed regarding practice patterns and utilization of these technologies. Subsequently, a roundtable was held to discuss survey results, explore current diagnostic and therapeutic challenges with these technologies, review the literature, and generate consensus-based recommendations. RESULTS: ARM identifies key pathophysiological abnormalities such as dyssynergic defecation, anal sphincter weakness, or rectal sensory dysfunction, and is a critical component of biofeedback therapy, an evidence-based treatment for patients with dyssynergic defecation and fecal incontinence. Additionally, ARM has the potential to enhance health-related quality of life and reduce healthcare costs. However, it has significant barriers that include a lack of education and training of healthcare providers regarding the utility and availability of ARM and biofeedback procedures, as well as challenges with condition-specific testing protocols and interpretation. Additional barriers include understanding when to perform, where to refer, and how to use these technologies, and confusion over billing practices. CONCLUSIONS: Overcoming these challenges with appropriate education, training, collaborative research, and evidence-based guidelines for ARM testing and biofeedback therapy could significantly enhance patient care of anorectal disorders.

Exploring the Gut-Brain Connection in Gastroparesis With Autonomic and Gastric Myoelectric Monitoring.

OBJECTIVE: The goal of this study was to identify autonomic and gastric myoelectric biomarkers from throughout the day that differentiate patients with gastroparesis, diabetics without gastroparesis, and healthy controls, while providing insight into etiology. METHODS: We collected 19 24-hour recordings of electrocardiogram (ECG) and electrogastrogram (EGG) data from healthy controls and patients with diabetic or idiopathic gastroparesis. We used physiologically and statistically rigorous models to extract autonomic and gastric myoelectric information from the ECG and EGG data, respectively. From these, we constructed quantitative indices which differentiated the distinct groups and demonstrated their application in automatic classification paradigms and as quantitative summary scores. RESULTS: We identified several differentiators that separate healthy controls from gastroparetic patient groups, specifically around sleep and meals. We also demonstrated the downstream utility of these differentiators in automatic classification and quantitative scoring paradigms. Even with this small pilot dataset, automated classifiers achieved an accuracy of 79% separating autonomic phenotypes and 65% separating gastrointestinal phenotypes. We also achieved 89% accuracy separating controls from gastroparetic patients in general and 90% accuracy separating diabetics with and without gastroparesis. These differentiators also suggested varying etiologies for different phenotypes. CONCLUSION: The differentiators we identified were able to successfully distinguish between several autonomic and gastrointestinal (GI) phenotypes using data collected while at-home with non-invasive sensors. SIGNIFICANCE: Autonomic and gastric myoelectric differentiators, obtained using at-home recording of fully non-invasive signals, can be the first step towards dynamic quantitative markers to track severity, disease progression, and treatment response for combined autonomic and GI phenotypes.

Efficacy and safety of olorinab, a full agonist of the cannabinoid receptor 2, for the treatment of abdominal pain in patients with irritable bowel syndrome: Results from a phase 2b randomized placebo-controlled trial (CAPTIVATE).

BACKGROUND: Olorinab is a highly selective, peripherally acting, full agonist of cannabinoid receptor 2. This study assessed the efficacy and safety of olorinab to treat abdominal pain in patients with irritable bowel syndrome with diarrhea (IBS-D) and constipation (IBS-C). METHODS: CAPTIVATE was a phase 2b, randomized, double-blind, placebo-controlled, parallel-group trial. Eligible participants aged 18-70 years with IBS-C and IBS-D diagnosed per Rome IV received olorinab 10 mg, 25 mg, or 50 mg three times daily (TID) or placebo TID for 12 weeks. The primary endpoint was the change in patient-reported average abdominal pain score (AAPS) from baseline to Week 12. KEY RESULTS: A total of 273 participants were randomized to receive olorinab 10 mg (n = 67), olorinab 25 mg (n = 67), olorinab 50 mg (n = 69), or placebo (n = 70). Although a treatment response was observed across all groups, the weekly change in average AAPS from baseline to Week 12 was not significantly different between placebo and any olorinab dose. In a prespecified subgroup analysis of participants with a baseline AAPS ≥6.5, olorinab 50 mg (n = 35) significantly improved AAPS compared with placebo (n = 30) (p = 0.014). Adverse event rates were comparable between olorinab and placebo and there were no reported serious adverse events or deaths. CONCLUSION AND INFERENCES: Although olorinab was well-tolerated and improved weekly AAPS, the primary endpoint was not met. However, in participants with moderate-to-severe pain at baseline (AAPS ≥6.5), olorinab 50 mg significantly improved weekly AAPS compared with placebo. CLINICALTRIALS: gov: NCT04043455.

Tolerability and Feasibility of the Upper Esophageal Sphincter Assist Device in Preventing Acute and Chronic Allograft Rejection Among Lung Transplant Recipients.

GOALS: We aimed to evaluate a novel upper esophageal sphincter (UES) assist device loaner program for the prevention of acute cellular rejection and chronic lung allograft dysfunction among lung transplant (LTx) recipients. BACKGROUND: Laryngopharyngeal reflux can lead to chronic microaspiration and LTx rejection. The UES assist device applies external pressure at the level of UES to decrease reflux. STUDY: We prospectively enrolled and issued UES assist devices to consecutive transplant patients referred for gastrointestinal motility testing from 2016 to 2020. Device tolerability was defined by successful utilization as a bridge to ambulatory pH monitoring and/or antireflux procedure, or as permanent therapy. Incidence of rejection was analyzed before, during, and after device implementation. RESULTS: Twenty-six participants were issued devices (15 pathologic, 5 physiological, 6 unknown reflux status), none of whom developed acute rejection episodes or chronic lung allograft dysfunction while using the device. Thirteen adopted the device promptly after transplantation (mean 1.7 mo) and remained free of rejection episodes over a mean 24.7 months of follow-up. Among those with pathologic reflux, lag time to device adoption strongly correlated with the development of rejection ( r =0.8, P =0.0006). There was no such correlation among those with physiological reflux. Five developed acute rejection after device return. CONCLUSIONS: The device was tolerated by a majority of LTx patients and appears feasible as a barrier measure in the prevention of rejection. Delayed treatment of laryngopharyngeal reflux may lead to early allograft failure; therefore, the UES assist device should be given important consideration in transplant protection.

Weight loss outcomes are not compromised in bariatric patients using cannabis.

BACKGROUND: The legalization of cannabis in several states has led to increased documented use in the population. Bariatric surgery patients are no exception with estimates of anywhere from 6 to 8%. Cannabis is known to be associated with increased appetite, mood disorders, hyperphagia, and rarely, hyperemesis, which can potentially affect post-surgical weight loss. We aim to study the differences in bariatric surgery outcomes between cannabis users and non-users. METHODS: A retrospective review identified patients undergoing bariatric surgery. Patients were divided into two groups, cannabis users (CU) and non-cannabis users (non-CU). Cannabis users (defined as using at least once weekly) and a group of non-users were called to obtain additional information. Primary outcome was weight loss. Secondary outcomes included incidence of post-operative nausea and vomiting (PONV), length of stay (LOS), readmission, and need for additional intervention. RESULTS: A cohort of 364 sleeve gastrectomy patients met inclusion criteria, 31 (8.5%) CU and 333 (91.5%) non-CU. There was no difference in EWL between CU and non-CU at 1 week, 1 month, 3 months, 6 months, 9 months, 1 year, and 2 years. However, the CU group trended towards greater EWL at 3 years (52.9% vs. 38.1%, p = 0.094) and at 5 years (49.8% vs. 32.7%, p = 0.068). There were no significant differences between CU and non-CU with respect to either incidence or severity of PONV at one year after surgery or longer follow-up. CONCLUSION: Cannabis users did not experience inferior weight loss after bariatric surgery despite common assumptions that appetite stimulation can lead to suboptimal weight loss outcomes. Our findings add to other work challenging this dogma. Larger, long-term, multicenter studies are warranted.

Robust Regression and Optimal Transport Methods to Predict Gastrointestinal Disease Etiology From High Resolution EGG and Symptom Severity.

OBJECTIVE: Gastric functional and motility disorders are highly prevalent, with gastroparesis (GP) and functional dyspepsia (FD), affecting 1.5-3% and 10% of the population, respectively. Multiple disease etiologies with overlapping symptoms, such as antral hypomotility, pylorospasm, autonomic dysfunction, and gastric myoelectric dysfunction underlie GP and FD. There is an unmet need to differentiate these etiologies non-invasively to tailor treatment strategies and predict treatment response. METHODS: We performed cutaneous high-resolution electrogastrogram (HR-EGG) recordings on 32 human subjects (controls, GP, and FD) and computed gastric slow wave propagation patterns. We implemented robust regression and clustering methods to identify one group of patients with symptoms well explained by spatial slow wave features and another with symptom severity significantly exceeding predictions from spatial slow wave features. Five patients were re-assessed with validated symptom questionnaires after pyloric and prokinetic interventions. RESULTS: A group of seven patients was identified whose spatial slow wave features lie within the same range as control subjects but whose symptom severity significantly exceeded what is predicted from spatial slow wave features. We hypothesize that gastric myoelectric dysfunction is not a prominent disease etiology in this group. A highly accurate regression holds in the other group of patients (r=0.8). Of the patients with repeat questionnaires, patients with symptom severity exceeding the regression line reported symptom improvement, whereas patients with symptoms in close proximity to the regression line experienced no improvement. CONCLUSION: These findings suggest that patients with symptom severity significantly exceeding the robust regression line have symptoms that cannot be explained by gastric myoelectric dysfunction alone, and vice versa. SIGNIFICANCE: This methodology may provide clinicians with an opportunity to screen patients to determine when existing interventions will be effective, and on the flipside, when slow wave restoration interventions, such as gastric neuromodulation, may be most effective in improving symptoms and quality of life.

Miniaturized wireless gastric pacing via inductive power transfer with non-invasive monitoring using cutaneous Electrogastrography.

BACKGROUND: Gastroparesis is a debilitating disease that is often refractory to pharmacotherapy. While gastric electrical stimulation has been studied as a potential treatment, current devices are limited by surgical complications and an incomplete understanding of the mechanism by which electrical stimulation affects physiology. METHODS: A leadless inductively-powered pacemaker was implanted on the gastric serosa in an anesthetized pig. Wireless pacing was performed at transmitter-to-receiver distances up to 20 mm, frequency of 0.05 Hz, and pulse width of 400 ms. Electrogastrogram (EGG) recordings using cutaneous and serosal electrode arrays were analyzed to compute spectral and spatial statistical parameters associated with the slow wave. RESULTS: Our data demonstrated evident change in EGG signal patterns upon initiation of pacing. A buffer period was noted before a pattern of entrainment appeared with consistent and low variability in slow wave direction. A spectral power increase in the EGG frequency band during entrainment also suggested that pacing increased strength of the slow wave. CONCLUSION: Our preliminary in vivo study using wireless pacing and concurrent EGG recording established the foundations for a minimally invasive approach to understand and optimize the effect of pacing on gastric motor activity as a means to treat conditions of gastric dysmotility.

Endoscopic ultrasound: a powerful tool to modify treatment algorithms in opioid-induced achalasia.

BACKGROUND: Opioid use in the U.S. has increased dramatically over the last 15 years, recently being declared a public health emergency. Opioid use is associated with esophageal dysmotility lending to a confusing clinical picture compared to true achalasia. Patients exhibit symptoms and elicit diagnostic results consistent with esophageal motility disorders, in particular type III achalasia. Modified therapeutic strategies and outcomes become challenging. Differentiating true achalasia from opioid-induced achalasia is critical. Conventional surgical interventions, i.e., myotomy, are ineffective in the absence of true achalasia. We assess the utility of esophageal muscle layer mapping with endoscopic ultrasound (EUS) in distinguishing primary from opioid-induced achalasia. METHODS: From 2016 to 2019, patients with abnormal manometry and suspected achalasia underwent esophagogastroduodenoscopy and EUS mapping of esophageal round muscle layer thickness. Maximum round layer thickness and length of round muscle layer thickness > 1.8 mm were collected and compared between opioid users and non-opioid users using Wilcoxon Rank sum test. RESULTS: 45 patients were included: 12 opioid users, 33 non-opioid users. Mean age 56.8 years (range 24-93), 53.3% male patients. Mean BMI in the opioid-induced achalasia group was 30.2 kg/m2, mean BMI in the primary achalasia group 26.8 kg/m2 (p = 0.11). In comparing endoscopic maximum round layer thickness between groups, non-opioid patients had a thicker round muscle layer (2.7 mm vs 1.8 mm, p = 0.05). Length of abnormally thickened esophageal muscle (greater than 1.8 mm) also differed between the two groups; patients on opioids had a shorter length of thickening (4.0 cm vs 0.0 cm, p = 0.04). Intervention rate was higher in the non-opioid group (p = 0.79). Of the patients that underwent therapeutic intervention, symptom resolution was higher in the non-opioid group (p = 0.002), while re-intervention post-procedure for persistent symptomatology was elevated in the opioid subset (p = 0.06). Patients in the opioid group were less likely to undergo invasive treatment (Heller). As of 2017 all interventions in the opioid group have been endoscopic. CONCLUSION: Endoscopic ultrasound is an essential tool that has improved our treatment algorithm for suspected achalasia in patients with chronic opioid usage. Incorporation of EUS findings into treatment approach may prevent unnecessary surgery in opioid users.

More beads, more peristaltic reserve, better outcomes: factors predicting postoperative dysphagia after magnetic sphincter augmentation.

INTRODUCTION: Magnetic sphincter augmentation (MSA) offers a minimally invasive anti-reflux alternative to fundoplication for gastroesophageal reflux disease. The most common side effect of MSA is dysphagia, which may require dilation or even device removal. The incidence of dysphagia may be reduced by MSA sizing and preoperative motility studies. Multiple rapid swallows (MRS) is a provocative maneuver during high-resolution esophageal manometry (HRM) that assesses peristaltic reserve. We evaluated factors predicting development of dysphagia following MSA. MATERIALS AND METHODS: A retrospective review of a prospectively maintained database identified patients undergoing MSA. Preoperative work-up included barium swallow, esophagogastroduodenoscopy, and esophageal manometry. Peristaltic augmentation was defined as a ratio > 1 of the distal contractile integral (DCI) following MRS and the mean DCI of the 10 baseline wet swallows during manometry. Demographics, MSA implant size, and postoperative symptom data were gathered on all patients. RESULTS: Sixty-eight patients underwent MSA. Mean age was 51.7 years, average BMI was 25.8 kg/m2. 15 (22.1%) of patients had severe dysphagia requiring endoscopic dilation. Peristaltic augmentation with MRS was significantly higher in patients without dysphagia (46.1% vs 6.3% p = 0.026). 33.3% of patients requiring dilatation exhibited complete absence of smooth muscle contraction following MRS (DCI = 0). The ratio of the DCI of MRS/wet swallows predicting dysphagia following MSA was 0.56. Patients with a small (12-14 beads) versus a larger MSA implant (15-17 beads) had a significantly higher rate of postoperative dysphagia (58.5% vs 30.0% p = 0.026). CONCLUSION: Adequate peristaltic reserve and larger device size correlate with decreased incidence of dysphagia following MSA implantation without compromising the anti-reflux barrier. Routine assessment of peristaltic reserve during preoperative HRM should be considered prior to MSA placement.

Robust Methods to Detect Abnormal Initiation in the Gastric Slow Wave from Cutaneous Recordings.

Upper gastrointestinal (GI) disorders are highly prevalent, with gastroparesis (GP) and functional dyspepsia (FD) affecting 3% and 10% of the US population, respectively. Despite overlapping symptoms, differing etiologies of GP and FD have distinct optimal treatments, thus making their management a challenge. One such cause, that of gastric slow wave abnormalities, affects the electromechanical coordination of pacemaker cells and smooth muscle cells in propelling food through the GI tract. Abnormalities in gastric slow wave initiation location and propagation patterns can be treated with novel pacing technologies but are challenging to identify with traditional spectral analyses from cutaneous recordings due to their occurrence at the normal slow wave frequency. This work advances our previous work in developing a 3D convolutional neural network to process multi-electrode cutaneous recordings and successfully classify, in silico, normal versus abnormal slow wave location and propagation patterns. Here, we use transfer learning to build a method that is robust to heterogeneity in both the location of the abnormal initiation on the stomach surface as well as the recording start times with respect to slow wave cycles. We find that by starting with training lowest-complexity models and building complexity in training sets, transfer learning one model to the next, the final network exhibits, on average, 80% classification accuracy in all but the most challenging spatial abnormality location, and below 5% Type-I error probabilities across all locations.

A Deep Convolutional Neural Network Approach to Classify Normal and Abnormal Gastric Slow Wave Initiation From the High Resolution Electrogastrogram.

OBJECTIVE: Gastric slow wave abnormalities have been associated with gastric motility disorders. Invasive studies in humans have described normal and abnormal propagation of the slow wave. This study aims to disambiguate the abnormally functioning wave from one of normalcy using multi-electrode abdominal waveforms of the electrogastrogram (EGG). METHODS: Human stomach and abdominal models are extracted from computed tomography scans. Normal and abnormal slow waves are simulated along stomach surfaces. Current dipoles at the stomachs surface are propagated to virtual electrodes on the abdomen with a forward model. We establish a deep convolutional neural network (CNN) framework to classify normal and abnormal slow waves from the multi-electrode waveforms. We investigate the effects of non-idealized measurements on performance, including shifted electrode array positioning, smaller array sizes, high body mass index (BMI), and low signal-to-noise ratio (SNR). We compare the performance of our deep CNN to a linear discriminant classifier using wave propagation spatial features. RESULTS: A deep CNN framework demonstrated robust classification, with accuracy above 90% for all SNR above 0 dB, horizontal shifts within 3 cm, vertical shifts within 6 cm, and abdominal tissue depth within 6 cm. The linear discriminant classifier was much more vulnerable to SNR, electrode placement, and BMI. CONCLUSION: This is the first study to attempt and, moreover, succeed in using a deep CNN to disambiguate normal and abnormal gastric slow wave patterns from high-resolution EGG data. SIGNIFICANCE: These findings suggest that multi-electrode cutaneous abdominal recordings have the potential to serve as widely deployable clinical screening tools for gastrointestinal foregut disorders.

Morphology of the Esophageal Hiatus: Is It Different in 3 Types of Hiatus Hernias?

BACKGROUND/AIMS: The esophageal hiatus is formed by the right crus of the diaphragm in the majority of subjects. Contraction of the hiatus exerts a sphincter-like action on the lower esophageal sphincter (LES). The aim is to study the hiatal anatomy (using CT scan imaging) and function (using high-resolution manometry [HRM]), and esophageal motor function in patients with sliding and paraesophageal hiatal hernia. METHODS: We assessed normal subjects (n = 20), patients with sliding type 1 hernia (n = 18), paraesophageal type 2 hernia (n = 19), and mixed type 3 hernia (n = 19). Hernia diagnosis was confirmed on the upper gastrointestinal series. The hiatal morphology was constructed from the CT scan images. The LES pressure and relaxation, percent peristalsis, bolus pressure, and hiatal squeeze pressure were assessed by HRM. RESULTS: The CT images revealed that the esophageal hiatus is formed by the right crus of the diaphragm in all normal subjects and 86% of hernia patients. The hiatus is elliptical in shape with a surface area of 1037 mm2 in normal subjects. The hiatal dimensions were larger in patients compared to normal subjects. The HRM revealed impaired LES relaxation and higher bolus pressure in patients with paraesophageal compared to the sliding hernia. The hiatal pinch on HRM was recognized in significantly higher number of patients with sliding as compared to paraesophageal hernia. CONCLUSIONS: Using a novel approach, we provide details of the esophageal hiatus in patients with various kinds of hiatal hernia. Impaired LES relaxation in paraesophageal hernia may play a role in its pathophysiology and genesis of symptoms.

Loop analysis of the anal sphincter complex in fecal incontinent patients using functional luminal imaging probe.

Cardiac loops have been used extensively to study myocardial function. With changes in cardiac pump function, loops are shifted to the right or left. Functional luminal imaging probe (FLIP) recordings allow for loop analysis of the anal sphincter and puborectalis muscle (PRM) function. The goal was to characterize anal sphincter area-pressure/tension loop changes in fecal incontinence (FI) patients. Fourteen healthy subjects and 14 patients with FI were studied. A custom-designed FLIP was placed in the vagina and then in the anal canal, and deflated in 20-ml steps, from 90 to 30 ml. At each volume, subjects performed maximal voluntary squeezes. Area-pressure (AP) and area-tension (AT) loops were generated for each squeeze cycle. Three-dimensional ultrasound imaging of the anal sphincter and PRM were obtained to determine the relationship between anal sphincter muscle damage and loop movements. With the increase in bag volume, AP loops and AT loops shifted to the right and upward in normal subjects (both anal and vaginal). The shift to the right was greater, and the upward movement was less in FI patients. The difference in the location of AP loops and AT loops was statistically significant at volumes of 50 ml to 90 ml (P < 0.05). A similar pattern was found in the vaginal loops. There is a significant relationship between the damage to the anal sphincter and PRM, and loop location of FI patients. We propose AP and AT loops as novel ways to assess the anal sphincter and PRM function. Such loops can be generated by real-time measurement of pressure and area within the anal canal.NEW & NOTEWORTHY We describe the use of area-pressure (AP) and area-tension (AT)-loop analysis of the anal sphincters and puborectalis muscles in normal subjects and fecal incontinent patients using the functional luminal imaging probe (FLIP). There are differences in the magnitude of the displacement of the loops with increase in the FLIP bag volume between normal subjects and patients with fecal incontinence. The latter group shifts more to the right in AP and AT space.

Bayesian inverse methods for spatiotemporal characterization of gastric electrical activity from cutaneous multi-electrode recordings.

Gastrointestinal (GI) problems give rise to 10 percent of initial patient visits to their physician. Although blockages and infections are easy to diagnose, more than half of GI disorders involve abnormal functioning of the GI tract, where diagnosis entails subjective symptom-based questionnaires or objective but invasive, intermittent procedures in specialized centers. Although common procedures capture motor aspects of gastric function, which do not correlate with symptoms or treatment response, recent findings with invasive electrical recordings show that spatiotemporal patterns of the gastric slow wave are associated with diagnosis, symptoms, and treatment response. We here consider developing non-invasive approaches to extract this information. Using CT scans from human subjects, we simulate normative and disordered gastric surface electrical activity along with associated abdominal activity. We employ Bayesian inference to solve the ill-posed inverse problem of estimating gastric surface activity from cutaneous recordings. We utilize a prior distribution on the spatiotemporal activity pertaining to sparsity in the number of wavefronts on the stomach surface, and smooth evolution of these wavefronts across time. We implement an efficient procedure to construct the Bayes optimal estimate and demonstrate its superiority compared to other commonly used inverse methods, for both normal and disordered gastric activity. Region-specific wave direction information is calculated and consistent with the simulated normative and disordered cases. We apply these methods to cutaneous multi-electrode recordings of two human subjects with the same clinical description of motor function, but different diagnosis of underlying cause. Our method finds statistically significant wave propagation in all stomach regions for both subjects, anterograde activity throughout for the subject with diabetic gastroparesis, and retrograde activity in some regions for the subject with idiopathic gastroparesis. These findings provide a further step towards towards non-invasive phenotyping of gastric function and indicate the long-term potential for enabling population health opportunities with objective GI assessment.

Spatial Patterns From High-Resolution Electrogastrography Correlate With Severity of Symptoms in Patients With Functional Dyspepsia and Gastroparesis.

BACKGROUND & AIMS: Invasive gastric electrical mapping has revealed spatial abnormalities of the slow wave in subjects with gastroparesis and functional gastrointestinal disorders. Cutaneous high-resolution electrogastrography (HR-EGG) is a non-invasive method that can detect spatial features of the gastric slow wave. We performed HR-EGG in subjects with active foregut symptoms to evaluate associations between gastric myoelectric abnormalities, symptoms (based on a validated questionnaire), and gastric emptying. METHODS: We performed a case-control study of 32 subjects, including 7 healthy individuals (controls), 7 subjects with functional dyspepsia and normal gastric emptying, and 18 subjects with gastroparesis, from a tertiary care program. All subjects were assessed by computed tomography imaging of the abdomen and HR-EGG and completed the PAGI-SYM questionnaire on foregut symptoms, which includes the gastroparesis cardinal symptom index. We performed volume reconstruction of the torso and stomach from computed tomography images to guide accurate placement of the HR-EGG array. RESULTS: Spatial slow-wave abnormalities were detected in 44% of subjects with foregut symptoms. Moreover, subjects with a higher percentage of slow waves with aberrant propagation direction had a higher total gastroparesis cardinal symptom index score (r = 0.56; P < .001) and more severe abdominal pain (r = 0.46; P = .009). We found no correlation between symptoms and traditional EGG parameters. CONCLUSIONS: In case-control study, we found that the genesis of symptoms of functional dyspepsia and gastroparesis is likely multifactorial, including possible contribution from gastric myoelectric dysfunction. Abnormal spatial parameters, detected by cutaneous HR-EGG, correlated with severity of upper gastrointestinal symptoms, regardless of gastric emptying. This noninvasive, repeatable approach might be used to identify patients for whom gastric myoelectric dysfunction contributes to functional dyspepsia and gastroparesis.

High-frequency ultrasound imaging of the anal sphincter muscles in normal subjects and patients with fecal incontinence.

INTRODUCTION: The current "gold standard" to diagnose anal sphincter morphology and disruptions utilizes low-frequency (3-9 MHz) ultrasound (US) imaging techniques that provide a general outline of the sphincter muscles, but not their microstructural details. High-frequency US transducers (7-15 MHz) have been used to study the muscle architecture (direction of muscle fascicles) in the limb muscle. AIMS: The goal of our study was to visualize the microstructural anatomy of the anal sphincters, specifically the external anal sphincter (EAS), using high-frequency US imaging. METHODS: Studies were conducted in asymptomatic female and male subjects and patients with fecal incontinence. US images were acquired using a low-frequency US (3-9 MHz) and high-frequency (7-15 MHz) US transducer. The latter was placed intra-anally to image the anal canal at 12, 9, 3, and 6 o'clock positions. RESULTS: The low-frequency US images revealed the general outline of the anal sphincter muscles. On the other hand, high-frequency imaging visualized muscle fascicles and connective tissue inside the external anal sphincter (EAS). In FI patients, there was loss of muscle fascicles and alteration in the echo-intensity pattern in the region of damaged EAS suggestive of muscle fibrosis. CONCLUSION: High-frequency ultrasound imaging is a powerful tool to visualize the microstructural details of the EAS. Our studies show that damage to the EAS muscle results in the alteration of its myoarchitecture, that is, loss of muscle fascicles and increase in the muscle connective tissue.