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Introduction Chronic idiopathic constipation (CIC) is a common and burdensome illness. We performed a cost-effectiveness analysis of the US Food and Drug Administration-approved CIC drugs to evaluate and quantify treatment preferences compared with usual care from insurer and patient perspectives. Methods We evaluated the subset of patients with CIC and documented failure of over-the-counter (OTC) osmotic or bulk-forming laxatives. A RAND/UCLA consensus panel of 8 neurogastroenterologists informed model design. Treatment outcomes and costs were defined using integrated analyses of registered clinical trials and the US Centers for Medicare and Medicaid Services-supported cost databases. Quality-adjusted life years (QALYs) were calculated using health utilities derived from clinical trials. A 12-week time horizon was used. Results With continued OTC laxatives, CIC-related costs were $569 from an insurer perspective compared with $3,154 from a patient perspective (considering lost wages and out-of-pocket expenses). CIC prescription drugs increased insurer costs by $618-$1,015 but decreased patient costs by $327-$1,117. Effectiveness of CIC drugs was similar (0.02 QALY gained/12 weeks or ∼7 healthy days gained/year). From an insurer perspective, prescription drugs (linaclotide, prucalopride, and plecanatide) seemed less cost-effective than continued OTC laxatives (incremental cost-effectiveness ratio >$150,000/QALY gained). From a patient perspective, the cost-effective algorithm started with plecanatide, followed by choosing between prucalopride and linaclotide starting at the 145-μg dose (favoring prucalopride among patients whose disease affects their work productivity). The patient perspective was driven by drug tolerability and treatment effects on quality of life. Discussion Addressing costs at a policy level has the potential to enable patients and clinicians to move from navigating barriers in treatment access toward truly optimizing treatment choice.

The pathophysiology of irritable bowel syndrome (IBS) is incompletely understood, but in at least some patients, alterations in the gut microbiome are likely to be etiologically relevant. The purpose of this review is to evaluate the available evidence to date for the use of prebiotics and probiotics in the treatment of IBS, with particular attention to broad themes in therapeutic rationale as well as critical gaps in the literature. A number of individual studies and meta-analyses have demonstrated efficacy in the use of prebiotics and probiotics for IBS. Even so, variability in study design, risk of bias, and short follow-up intervals limit the ability to draw robust conclusions in aggregate. More research is needed to understand the intricacy of the gut microbiome and how it relates to IBS symptomatology, but the effectiveness of prebiotic and probiotic agents demonstrated so far implies a worthy therapeutic signal within the noise.

Gastroesophageal reflux disease (GERD) is prevalent and may be associated with both esophageal and extraesophageal syndromes, which include various pulmonary conditions. GERD may lead to pulmonary complications through the "reflux" (aspiration) or "reflex" (refluxate-triggered, vagally mediated airway spasm) mechanisms. While GERD may cause or worsen pulmonary disorders, changes in respiratory mechanics due to lung disease may also increase reflux. Typical esophageal symptoms are frequently absent and objective assessment with reflux monitoring is often needed for diagnosis. Impedance monitoring should be considered in addition to traditional pH study due to the involvement of both acidic and weakly acidic/nonacidic reflux. Antireflux therapy may improve outcomes of some pulmonary complications of GERD, although careful selection of a candidate is paramount to successful outcomes. Further research is needed to identify the optimal testing strategy and patient phenotypes that would benefit from antireflux therapy to improve pulmonary outcomes.

Eosinophilic esophagitis (EoE) is a clinicopathologic disease characterized by symptoms of esophageal dysfunction and esophageal eosinophilia. In the last decade, there has been a dramatic increase in its prevalence for reasons that are not completely understood. The underlying pathophysiology involves an antigen-mediated TH 2 immune response that draws eosinophils to the esophagus, causing mucosal inflammation, esophageal remodeling, and fibrosis. This ultimately leads to esophageal dysfunction that most commonly manifests as dysphagia. In this review, we will discuss updates on key questions regarding the diagnosis and treatment of EoE.

Impedance has traditionally been employed in esophageal disease as a means to assess bolus flow and reflux episodes. Recent and ongoing research has provided new and novel applications for this technology. Measurement of esophageal mucosal impedance, via either multichannel intraluminal impedance catheters or specially designed endoscopically deployed impedance catheters, provides a marker of mucosal integrity. Mucosal impedance has been shown to segregate gastroesophageal reflux disease (GERD) and eosinophilic esophagitis from non-GERD controls and may play a role in predicting response to reflux intervention. More data are needed with regard to other esophageal subgroups, outcome studies, and functional disease. Our paper reviews the history of impedance in esophageal disease, the means of assessing baseline and mucosal impedance, data with regard to the newly developed mucosal impedance probes, the clinical utility of mucosal impedance in specific clinical conditions, and limitations in our existing knowledge, along with suggestions for future studies.

Nutritional ingredients, including various fibers, herbs, and botanicals, have been historically used for various ailments. Their enduring appeal is predicated on the desire both for more natural approaches to health and to mitigate potential side effects of more mainstream treatments. Their use in individuals experiencing upper gastrointestinal (GI) complaints is of particular interest in the scientific space as well as the consumer market but requires review to better understand their potential effectiveness. The aim of this paper is to review the published scientific literature on nutritional ingredients for the management of upper GI complaints. We selected nutritional ingredients on the basis of mentions within the published literature and familiarity with recurrent components of consumer products currently marketed. A predefined literature search was conducted in Embase, Medline, Derwent drug file, ToXfile, and PubMed databases with specific nutritional ingredients and search terms related to upper GI health along with a manual search for each ingredient. Of our literature search, 16 human clinical studies including nine ingredients met our inclusion criteria and were assessed in this review. Products of interest within these studies subsumed the categories of botanicals, including fiber and combinations, and non-botanical extracts. Although there are a few ingredients with robust scientific evidence, such as ginger and a combination of peppermint and caraway oil, there are others, such as melatonin and marine alginate, with moderate evidence, and still others with limited scientific substantiation, such as galactomannan, fenugreek, and zinc-l-carnosine. Importantly, the paucity of high-quality data for the majority of the ingredients analyzed herein suggests ample opportunity for further study. In particular, trials with appropriate controls examining dose–response using standardized extracts and testing for specific benefits would yield precise and effective data to aid those with upper GI symptoms and conditions.

Background Esophagogastric junction outflow obstruction (EGJOO) has a variable disease course. Currently, barium swallow (BaS) and manometric parameters are used to characterize clinically significant EGJOO. The esophagogastric junction distensibility index (EGJ-DI) measured via functional lumen imaging probe (FLIP) can provide complementary information. Our aim was to assess symptom response in patients with EGJOO and an abnormal EGJ-DI after botulinum toxin (BT) treatment. Methods A prospective cohort study of adults with idiopathic EGJOO was performed from September 2019 to March 2021. Patients with dysphagia underwent upper endoscopy with FLIP. If the EGJ-DI was abnormally low, BT was injected. Data examined included demographics, medical history, endoscopic and FLIP findings, BaS, manometry, and Eckardt score (ES). ES improvement was assessed via paired samples t-test. Pearson’s chi-square tests were used to assess for associations. Results Of the 20 patients, 75% had an abnormal EGJ-DI and underwent BT injections. Mean ES for patients with abnormal EGJ-DIs significantly improved from baseline to 1, 3, and 6 month follow-up (P-values: 0.01, 0.05, and 0.02, respectively). There was a significant association between an abnormal EGJ-DI with delayed bolus transit and presence of rapid drink challenge panesophageal pressurization on manometry: P = 0.03 and P = 0.03. Conclusion This prospective study revealed that an abnormal EGJ-DI can guide BT as assessed via symptomatic response. Additionally, abnormal EGJ-DI measurements were significantly associated with other parameters used previously to determine clinically relevant EGJOO. Larger follow-up studies are warranted to further elucidate guidance for therapy in EGJOO.

GOALS The goal of this study was to identify factors impacting the quality of bowel preparation in an urban tertiary care setting. BACKGROUND Inadequate bowel preparation is encountered in 17% to 32% of colonoscopies performed in the United States. Suboptimal colonic visualization reduces the yield of screening colonoscopies and increases healthcare costs because of longer procedure times and aborted procedures. STUDY We performed a cross-sectional survey in patients undergoing outpatient colonoscopy within the Johns Hopkins Health System. A Boston Bowel Preparation Score (BBPS) score of

Chronic idiopathic constipation (CIC) is a common and burdensome illness. We performed a cost-effectiveness analysis of the US Food and Drug Administration-approved CIC drugs to evaluate and quantify treatment preferences compared with usual care from insurer and patient perspectives.We evaluated the subset of patients with CIC and documented failure of over-the-counter (OTC) osmotic or bulk-forming laxatives. A RAND/UCLA consensus panel of 8 neurogastroenterologists informed model design. Treatment outcomes and costs were defined using integrated analyses of registered clinical trials and the US Centers for Medicare and Medicaid Services-supported cost databases. Quality-adjusted life years (QALYs) were calculated using health utilities derived from clinical trials. A 12-week time horizon was used.With continued OTC laxatives, CIC-related costs were $569 from an insurer perspective compared with $3,154 from a patient perspective (considering lost wages and out-of-pocket expenses). CIC prescription drugs increased insurer costs by $618-$1,015 but decreased patient costs by $327-$1,117. Effectiveness of CIC drugs was similar (0.02 QALY gained/12 weeks or ∼7 healthy days gained/year). From an insurer perspective, prescription drugs (linaclotide, prucalopride, and plecanatide) seemed less cost-effective than continued OTC laxatives (incremental cost-effectiveness ratio$150,000/QALY gained). From a patient perspective, the cost-effective algorithm started with plecanatide, followed by choosing between prucalopride and linaclotide starting at the 145-μg dose (favoring prucalopride among patients whose disease affects their work productivity). The patient perspective was driven by drug tolerability and treatment effects on quality of life.Addressing costs at a policy level has the potential to enable patients and clinicians to move from navigating barriers in treatment access toward truly optimizing treatment choice.

Beyond the most common etiologies of gastroparesis, there are several rarer causes that merit consideration in the appropriate clinical context. These include medications with deleterious effects on gastric motility (e.g. opiates, cannabinoids, anticholinergic agents), distal obstruction, connective tissue disorders, autoimmune autonomic neuropathy, malignancy and paraneoplastic syndromes, systemic neurologic disorders, pancreatitis, ischemia, non-diabetic endocrinopathy, and renal failure. Some of these associations are tenuous and/or governed by speculative mechanistic explanations that may be clarified through future investigation. Recognizing a rare or unusual cause of gastroparesis can offer up unique pathways toward effective symptom management.

The functional lumen imaging probe (FLIP) is a diagnostic tool that utilizes impedance planimetry to allow the assessment of luminal diameter and distensibility. It has been used primarily in esophageal diseases, in particular, in the assessment of achalasia, esophagogastric junction outflow obstruction, and eosinophilic esophagitis (EoE). The usage and publications have increased over the past decade and it is now an essential tool in the armamentarium of the esophagologist. Indications are emerging outside of the esophagus, in particular with regard to gastroparesis. Our paper will review the history of FLIP, optimal current usage, data for key esophageal disorders (including achalasia, reflux, and EoE), data for nonesophageal disorders, and our sense as to whether FLIP is ready for prime time, as well as gaps in evidence and suggestions for future research.

Background/purpose Symptoms of gastrointestinal dysmotility are common among patients with systemic sclerosis (SSc), and the management of severe cases is often limited by a relative lack of effective interventions. The objective of this case series was to review our experience with pyridostigmine as a treatment for patients with SSc and symptomatic gastrointestinal disease. Methods This study evaluated rates of symptom improvement, side effects, medication adherence, and dose ranges for SSc patients prescribed pyridostigmine for refractory gastrointestinal symptoms over a 10-year period at a quaternary referral center. Patients were defined as responders if they remained on pyridostigmine for at least 4 weeks and clinical benefit was documented by the recorded response of the patient or by the treating physician Results Of 31 patients treated with pyridostigmine for at least 4 weeks, 51.6% reported symptomatic improvement. Constipation was the most commonly improved symptom based on prevalence prior to therapy (noted by 6/20 patients suffering with constipation). Fifteen of 31 patients reported adverse effects, most commonly diarrhea. Throughout the duration of follow-up (median 126 days, range: 28–506 days), pyridostigmine was continued by 81.3% of patients who reported symptomatic benefit and 58.1% of patients overall. Conclusions Pyridostigmine holds promise for the treatment of various gastrointestinal symptoms in SSc patients, particularly in patients with refractory constipation. Though side effects may limit its use, most patients who experienced benefit chose to continue therapy.

Luminal distensibility measurement has demonstrated relevance to various disease processes, though its effects on clinical decision-making have been less well understood. This study aims to characterize the clinical impact of impedance planimetry measurement as well as the learning curve associated with its use in the esophagus. A single provider performed distensibility measurement in conjunction with upper endoscopy for a variety of clinical indications with the functional lumen imaging probe (FLIP) over a period of 21 months. Procedural data were prospectively collected and, along with medical records, retrospectively reviewed. Seventy-three procedures (70 patients) underwent esophageal distensibility measurement over the timeline of this study. The most common procedural indications were known or suspected achalasia (32.9%), dysphagia with connective tissue disease (13.7%), eosinophilic esophagitis (12.3%), and dysphagia with prior fundoplication (9.6%). FLIP results independently led to a change in management in 29 (39.7%) cases and supported a change in management in an additional 15 (20.5%) cases. The most common change in management was a new or amended therapeutic procedure (79.5%). Procedural time added by distensibility measurement was greater among earlier cases than among later cases. The median time added overall was 5 minutes and 46 seconds. Procedural time added varied significantly by procedural indication, but changes in management did not. Distensibility measurement added meaningful diagnostic information that impacted therapeutic decision-making in the majority of cases in which it was performed. Procedural time added by this modality is typically modest and decreases with experience.

Gastroparesis is a syndrome that can be difficult to treat effectively and likely represents the common clinical presentation of multiple underlying mechanisms. One of these presumed mechanisms involves pyloric dysfunction, tied perhaps to spasm or fibrosis, manifesting as functional gastric outlet obstruction. Various diagnostic modalities have been used to better characterize this hypothesized abnormality, including most recently antroduodenal manometry and impedance planimetry. A variety of therapeutic interventions specific to the pylorus have also been proposed in the last several years, including intrapyloric injections of botulinum toxin, transpyloric stenting, surgical pyloroplasty, and endoscopic pyloromyotomy. The clinical application of these maneuvers has been mostly empiric thus far, but efforts are ongoing to identify the subset of patients whose physiology best positions them to benefit from such therapy. Early results for many of these interventions have been promising and will serve as the basis for larger and more systematic research frameworks moving forward.

Popular remedies are of ongoing interest to patients experiencing common esophageal symptoms, particularly as typical pharmacologic interventions have been subject to increased scrutiny. Herein we summarize the available data regarding potential risks and benefits of several such remedies. With emphasis on reflux and non-cardiac chest pain, research is ongoing into the clinical utility and diverse physiologic mechanisms underlying a variety of complementary and alternative modalities, including dietary manipulation, apple cider vinegar, melatonin, acupuncture, and various herbal products (rikkunshito, STW 5, slippery elm, licorice, and peppermint oil, among others). A substantial gap persists between anecdotal and empirical understandings of the majority of non-pharmacologic remedies for esophageal symptoms. This landscape of popular treatments nevertheless raises several interesting mechanistic hypotheses and compelling opportunities for future research.

Esophagogastric junction outflow obstruction (EGJOO) is an abnormal finding on high-resolution manometry (HRM) characterized by an elevated median integrated relaxation pressure with some intact peristalsis.1 EGJOO is associated with heterogeneous symptoms, disease course, and response to treatment.1-4 It can be idiopathic or secondary with causes including malignancy, infiltrative disease, or structural etiology.1,3 Therefore, Chicago Classification of Esophageal Motility Disorders version 3.0 (CC v3.0) states a finding of EGJOO should prompt further investigation with cross-sectional imaging (CSI): endoscopic ultrasound (EUS) or computed tomography (CT) scan. However, there are limited data on the added yield of CSI to conventional modalities, namely esophagogastroduodenoscopy (EGD) and barium esophagram (BE). In previous studies, yield was small or unspecified.2,5-8 The aim of this study was to examine the yield of CSI for diagnosing secondary causes of EGJOO.

This review addresses the similarities and differences between the spastic esophageal disorders, including jackhammer esophagus, distal esophageal spasm (DES), and type III (spastic) achalasia. The pathophysiology, diagnosis, and treatment of each separate disorder are discussed herein, with an emphasis on overlapping and discordant features. The Chicago Classification is a hierarchical organizational scheme for esophageal motility disorders, currently in its third iteration, with direct impact on the definitions of these three disorders. Complementary diagnostic tools such as impedance planimetry and novel manometric parameters continue to evolve. The suite of potential treatments for these disorders is also expanding, with progressive interest in the role of peroral endoscopic myotomy alongside established pharmacologic and mechanical interventions. Although jackhammer esophagus, distal esophageal spasm, and type III achalasia frequently overlap in terms of their clinical presentation and available management approaches, the divergences in their respective diagnostic criteria suggest that additional study may reveal additional mechanistic distinctions that lead in turn to further refinements in therapeutic decision-making.

Health and High Water Under the strange gravity of the Anthropocene era, clinical medicine has begun to feel a bit weightless. What does it mean to engage with individual distress inside a hospital...

Background & Aims Endoscopic ultrasound (EUS) often is used to stage rectal cancer and thereby guide treatment. Prior assessments of its accuracy have been limited by small sets of data collected from tumors of varying stages. We aimed to characterize the diagnostic performance of EUS analysis of rectal cancer, paying particular attention to determining whether patients should undergo primary surgical resection. Methods We performed a retrospective observational study using procedural databases and electronic medical records from 4 academic tertiary-care hospitals, collecting data on EUS analyses from 2000 through 2012. Data were analyzed from 86 patients with rectal cancer initially staged as T2N0 by EUS. The negative predictive value (NPV) was calculated by comparing initial stages determined by EUS with those determined by pathology analysis of surgical samples. Logistic regression models were used to assess variation in diagnostic performance with case attributes. Results EUS excluded advanced tumor depth with an NPV of 0.837 (95% confidence interval [CI], 0.742–0.908), nodal metastasis with an NPV of 0.872 (95% CI, 0.783–0.934), and both together with an NPV of 0.767 (95% CI, 0.664–0.852) compared with pathology analysis. Incorrect staging by EUS affected treatment decision making for 20 of 86 patients (23.3%). Patient age at time of the procedure correlated with the NPV for metastasis to lymph node, but no other patient features were associated significantly with diagnostic performance. Conclusions Based on a multicenter retrospective study, EUS staging of rectal cancer as T2N0 excludes advanced tumor depth and nodal metastasis, respectively, with an approximate NPV of 85%, similar to that of other modalities. EUS has an error rate of approximately 23% in identifying disease appropriate for surgical resection, which is lower than previously reported.

Background and Aims: ERCP is challenging in patients with Roux-en-Y gastric bypass (RYGB) anatomy. EUS-guided gastrogastrostomy (GG) creation is a promising novel technique to access the excluded stomach to facilitate conventional ERCP. We aimed to compare procedural outcomes and adverse events (AEs) between EUS-guided GG-assisted ERCP (EUS-GG-ERCP) and enteroscopy-assisted ERCP (e-ERCP) in patients with RYGB. Methods: Patients with RYGB anatomy who underwent EUS-GG-ERCP or e-ERCP between 2014 and 2016 at 5 tertiary centers were included. The primary outcome was technical success of ERCP, defined as successful cannulation of the selected duct with successful intervention as intended. Secondary outcomes included total procedural time (in the EUS-GG group, total procedural time included EUS-GG creation plus ERCP procedure time), length of hospital stay, and rate/severity of AEs graded according to the American Society for Gastrointestinal Endoscopy lexicon. Results: A total of 60 patients (mean age, 57.2 ± 13.2; 75% women) were included, of whom 30 (50%) underwent EUS-GG-ERCP and 30 (50%) underwent e-ERCP (double-balloon enteroscope ERCP, 19; single-balloon enteroscope ERCP, 11). The technical success rate was significantly higher in the EUS-GG-ERCP versus the e-ERCP group (100% vs 60.0%, P

Impedance planimetry measures tissue wall distensibility as a function of pressure and cross-sectional area. Recent interest in this technique’s relevance to the gastrointestinal tract has been accelerated by the availability of the functional lumen imaging probe, a catheter-based system that dynamically quantitates these biomechanical properties. Herein, we review the device’s particular utility in the setting of esophageal pathology, including processes affecting the esophageal body as well as the upper and lower esophageal sphincters. An expanding suite of disease-specific indications for impedance planimetry includes achalasia, gastroesophageal reflux disease, and eosinophilic esophagitis. The technique has also demonstrated a role in the intraoperative guidance of therapy and in the definition of hitherto unrecognized patterns of esophageal dysmotility. Device-specific technology remains in active evolution, which, in conjunction with progressively larger datasets, sets the stage for broader clinical applicability in the near future.

Given that the first experiments involving submucosal endoscopic esophageal myotomy in a porcine model were published in 2007, the interval uptake of peroral endoscopic myotomy (POEM) into clinical practice has been impressively swift. While the procedure remains limited to specialized practitioners and centers, it has become a valuable therapeutic option for the management of achalasia with outcomes that rival benchmarks established by more conventional surgical alternatives. Historical perspective helps to contextualize POEM as the conceptual outgrowth of a much longer therapeutic lineage rather than a de novo innovation to be added to the proceduralist’s armamentarium. Reflecting on the specific differences between submucosal endoscopic myotomy and the interventions (both experimental and established) that preceded it allows for a clearer understanding of the ways in which POEM represents a novel therapeutic paradigm, for spastic esophageal disorders in particular and for endoscopy in general. Looking ahead, distant milestones in this conceptual evolution might include technical elaboration made possible by novel endoscopic devices or, intriguingly, molecular therapies that might render endoscopic therapy for achalasia obsolete.

A limited number of medications are typically considered for the management of hepatic encephalopathy occurring as a complication of transjugular intrahepatic portosystemic shunt (TIPS) placement. Multiple alternative compounds aimed at disrupting ammoniagenesis are or will soon be available, though their use tends to be limited by a lack of large data sets and of clinical awareness. In this review, we provide a targeted overview of the mechanisms and availability of five anti-ammoniagenic compounds (sodium phenylbutyrate, glycerol phenylbutyrate, sodium benzoate, L-ornithine L-aspartate, and ornithine phenylacetate) identified as possibly useful alternative therapeutic agents for cirrhotic encephalopathy. Three of these medications have been FDA approved for use in congenital urea cycle disorders only, while two are under active investigation for use in cirrhotic patients. In spite of limitations posed by cost and comorbidities, familiarity with these options may prove beneficial in cases refractory to conventional management.

Background Esophagogastric junction (EGJ) outflow obstruction (EGJOO) is characterized by impaired EGJ relaxation with intact or weak peristalsis. Our aims were to evaluate: (i) prevalence, (ii) yield of fluoroscopy, endoscopy, and endoscopic ultrasound (EUS), (iii) outcomes, and (iv) whether this data differed based on quantitative EGJ relaxation. Methods Studies that met criteria for EGJOO were identified. Demographics, encounters, endoscopy, radiology, treatment decisions, and outcomes were extracted. Key Results Sixty studies were identified. Dysphagia was the most common symptom. Forty patients underwent barium esophagram (BE): normal (11), hiatal hernia (20), spasm/dysmotility (17), EGJ narrowing (10), compression (2), Schatzki's ring (5), malrotation (1), gastric volvulus (1), mass (1). Esophagogastroduodenoscopy (EGD) was performed in 41 patients: normal (19), hiatal hernia (13), Schatzki's ring (6), esophagitis (3), esophageal candidiasis (3), mass (1). EUS was performed in 20 patients and was frequently normal. Twenty-two patients underwent intervention. While transient improvement was noted in the majority, persistent improvement was seen in only one of nine patients (dilatation), four of six patients (botulinum toxin), and three patients who underwent per-oral endoscopic myotomy. No patients treated with medical therapy alone had improvement in dysphagia. There was no difference in symptoms or outcomes based on quantitative EGJ relaxation. Conclusions & Inferences The manometric criterion EGJOO defines a heterogeneous clinical group. While BE, EGD, and EUS all provide complementary information, a significant percentage of these studies will be normal. For patients with dysphagia, outcome may depend on EGJ disruption. There were no differences in symptoms our outcomes based on quantitative EGJ relaxation.

The prevalence and complexity of obesity and its associated metabolic complications highlight the importance of building a rigorous investigative framework for the development of novel weight loss therapies. Device-based interventions in particular constitute a market poised for rapid expansion in the coming years. Optimizing outcomes for this new class of therapies requires attention to an evolving taxonomy of subdivisions within the broader obesity phenotype and a means for stratifying patients toward maximally effective interventions. Extant bariatric devices implicitly prioritize anatomic variables as surrogates for physiology, a somewhat arbitrary assumption that merits empiric validation. Utilizing the governing principles of systems biology and recent innovations in clinical trial design, a robust and precise research infrastructure can and should be developed to more effectively mitigate this contemporary epidemic.

Among the many inflammatory processes that may account for esophageal symptoms, infection represents an important etiologic category with numerous clinically relevant subdivisions. While features of the history and physical exam are informative, diagnosis often hinges on endoscopic visualization and histopathologic analysis. This chapter will review in series the most clinically relevant causative agents for infectious esophagitis, with specific diagnostic and therapeutic features of note divided into one of two immune milieus. Our discussion focuses primarily on Candida species, herpes simplex virus, and cytomegalovirus as the most common causes of infectious esophagitis while also addressing a number of less common pathogens worth keeping in mind.

The upper esophageal sphincter constitutes an important anatomic and functional landmark in the physiology of pharyngeal swallowing. A variety of clinical circumstances may call for a dedicated evaluation of this mechanism, from the etiologic evaluation of indeterminate symptoms to the generation of complex locoregional therapeutic strategies. Multiple diagnostic tools exist for the assessment of pharyngeal swallowing generally and of upper esophageal sphincter function specifically, some well established and others not yet settled into routine practice. This report reviews five specific modalities for use in making this assessment, outlining the strengths, weaknesses, and logistical considerations of each with respect to its potential use in clinical settings. In many cases, these studies will provide complementary information regarding pharyngeal function, suggesting the relative advantage of a multimodal evaluation.

The human gut has been viewed for centuries as a potential mediator of systemic disease. The theory of autointoxication, which found its clearest articulation in the late nineteenth and early twentieth centuries, focused on altered bowel habits as the cause of widespread physical decay and advocated for the pursuit of health through regular defecation. More recently, under the banner of the microbiome, research on commensal bacteria makes a similar case for associations between alimentary dynamics and illness manifestations far outside the gastrointestinal tract. Surface distinctions between these two conceptual frameworks are apparently antipodal, the former championing emptiness and sterility, the latter abundance and restoration. Within both models, however, persists a common anxiety about the detrimental effects of civilisation on the body in relation to the natural world. As scientific understanding of the microbiome continues to mature, acknowledging the historical and moral parameters of its borrowed ecological idiom may facilitate critical distinctions between what is true and what feels like it should be.