Achalasia: physiology and diagnosis Rieder, Erwin; Fernandez‐Becker, Nielsen Q.; Sarosiek, Jerzy ...
Annals of the New York Academy of Sciences,
December 2020, Letnik:
1482, Številka:
1
Journal Article
Recenzirano
Achalasia is a rare motility disorder with incomplete relaxation of the lower esophageal sphincter and ineffective contractions of the esophageal body. It has been hypothesized that achalasia does ...not result from only one pathway but rather involves a combination of infectious, autoimmune, and familial etiological components. On the basis of other observations, a novel hypothesis suggests that a muscular form of eosinophilic esophagitis is involved in the pathophysiology of achalasia in some patients. This appears to progressively diminish the myenteric plexus at stage III, gradually destroy it at stage II, and finally eliminate it at stage I, the most advanced and final stage of achalasia. Although high‐resolution manometry has identified these three different types of achalasia, another subset of patients with a normal‐appearing sphincter relaxation has been proposed. Provocative maneuvers, such as the rapid drinking challenge, have recently been demonstrated to improve diagnosis in certain borderline patients, but have to be studied in more detail. However, whether the different types of achalasia will have a long‐term impact on tailored therapies is still a matter of debate. Additionally, novel aspects of the standard timed barium swallow appear to be an important adjunct of diagnosis, as it has been shown to have a diagnostic as well as a predictive value.
Eosinophilic esophagitis (EoE) is an antigen-mediated esophageal disease defined by the presence of esophageal eosinophilia and symptoms of esophageal dysfunction. The pathophysiology involves an ...allergen-driven Th2 T cell response that triggers infiltration of eosinophils into the esophagus leading to inflammation, remodeling, and fibrosis. This results in disruption of esophageal function and accompanying symptoms - most notably dysphagia. Effective therapies target inflammation or fibrostenotic complications and include proton pump inhibitors, swallowed topical steroids, dietary exclusion, and dilation. Clinical trials testing promising biologic therapies are ongoing.
Background
Vitamin‐D is essential for musculoskeletal health. We aimed to determine whether patients with fecal incontinence (FI): (1) are more likely to have vitamin‐D deficiency and, (2) have ...higher rates of comorbid medical conditions.
Methods
We examined 18‐ to 90‐year‐old subjects who had 25‐hydroxy vitamin‐D levels, and no vitamin‐D supplementation within 3 months of testing, in a large, single‐institutional electronic health records dataset, between 2017 and 2022. Cox proportional hazards survival analysis was used to assess association of vitamin‐D deficiency on FI.
Key Results
Of 100,111 unique individuals tested for serum 25‐hydroxy vitamin‐D, 1205 (1.2%) had an established diagnosis of FI. Most patients with FI were female (75.9% vs. 68.7%, p = 0.0255), Caucasian (66.3% vs. 52%, p = 0.0001), and older (64.2 vs. 53.8, p < 0.0001). Smoking (6.56% vs. 2.64%, p = 0.0001) and GI comorbidities, including constipation (44.9% vs. 9.17%, p = 0.0001), irritable bowel syndrome (20.91% vs. 3.72%, p = 0.0001), and diarrhea (28.55% vs. 5.2%, p = 0.0001) were more common among FI patients. Charlson Comorbidity Index score was significantly higher in patients with FI (5.5 vs. 2.7, p < 0.0001). Significantly higher proportions of patients with FI had vitamin‐D deficiency (7.14% vs. 4.45%, p < 0.0001). Moreover, after propensity‐score matching, rate of new FI diagnosis was higher in patients with vitamin‐D deficiency; HR 1.9 (95% CI 1.14–3.15), p = 0.0131.
Conclusion & Inferences
Patients with FI had higher rates of vitamin‐D deficiency along with increased overall morbidity. Future research is needed to determine whether increased rate of FI in patients with vitamin‐D deficiency is related to frailty associated with increased medical morbidities.
Patients with fecal incontinence (FI) had higher rates of vitamin‐D deficiency along with increased overall morbidity. These findings highlight the importance of evaluation for vitamin‐D deficiency in adults, especially in frail patients with multiple chronic conditions, who are at high risk of FI.
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.
Our paper will review the history of the functional luminal imaging probe (FLIP), optimal current usage, data for key esophageal disorders (including achalasia, reflux, and eosinophilic esophagitis), 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
Gastroparesis, a chronic motility disorder characterized by delayed gastric emptying, abdominal pain, nausea, and vomiting, remains largely unexplained. Medical therapy is limited, ...reflecting the complex physiology of gastric sensorimotor function. Vagus nerve stimulation is an attractive therapeutic modality for gastroparesis, but prior methods required invasive surgery. In this open‐label pilot study, we aimed to assess the benefit of non‐invasive vagal nerve stimulation in patients with mild to moderate idiopathic gastroparesis.
Methods
Patients self‐administered the gammaCore vagal nerve stimulator for 4 weeks. The gastroparesis cardinal symptom index daily diary (GCSI‐dd) was assessed during a two‐week run‐in period, ≥4 weeks of therapy, and 4 weeks after therapy was completed. Gastric emptying and autonomic function testing were also performed. The primary endpoint was an absolute reduction in CGSI‐dd of 0.75 after nVNS.
Results
There was a total improvement in symptom scores (2.56 ± 0.76 to 1.87 ± 1.05; P = .01), with 6/15 (40%) participants meeting our primary endpoint. Therapy was associated with a reduction in gastric emptying (T1/2 155 vs 129 minutes; P = .053, CI −0.4 to 45). Therapy did not correct autonomic function abnormalities, but was associated with modulation of reflex parasympathetic activity.
Conclusions
Short‐term non‐invasive vagal nerve stimulation led to improved cardinal symptoms and accelerated gastric emptying in a subset of patients with idiopathic gastroparesis. Responders had more severe gastric delay at baseline and clinical improvement correlated with duration of therapy, but not with improvements in gastric emptying. Larger randomized sham‐controlled trials of greater duration are needed to confirm the results of this pilot study.
Short‐term non‐invasive vagal nerve stimulation can improve cardinal symptoms and accelerate gastric emptying in patients with idiopathic gastroparesis. Through its neuromodulatory and pro‐kinetic effects, non‐invasive vagal nerve stimulation may offer a safe and well tolerated therapy for the treatment of gastroparesis.
Background
Integrated relaxation pressure (IRP) calculation depends on the selection of a single gastric reference sensor. Variable gastric pressure readings due to sensor selection can lead to ...diagnostic uncertainty. This study aimed to examine the effect of gastric reference sensor selection on IRP measurement and diagnosis.
Methods
We identified high‐resolution manometry (HRM) conducted between January and November 2017 with at least six intragastric reference sensors. IRP measurements and Chicago Classification 3.0 (CCv3) diagnoses were obtained for each of six gastric reference sensors. Studies were categorized as “stable” (no change in diagnosis) or “variable” (change in diagnosis with gastric reference selection). Variable diagnoses were further divided into “variable normal/dysmotility” (≥1 normal IRP measurement and ≥1 CCv3 diagnosis), or “variable dysmotility” (≥1 CCv3 diagnosis, only elevated IRP measurements). Bland–Altman plots were used to compare IRP measurements within HRM studies.
Key Results
The analysis included 100 HRM studies, among which 18% had variable normal/dysmotility, and 10% had variable dysmotility. The average IRP difference between reference sensors was 6.7 mmHg for variable normal/dysmotility and 5.9 mmHg for variable dysmotility. The average difference between the proximal‐most and distal‐most sensors was −1.52 mmHg (lower limit of agreement −10.03 mmHg, upper limit of agreement 7.00 mmHg).
Conclusions & Inferences
IRP values can vary greatly depending on the reference sensor used, leading to inconsistent diagnoses in 28% of HRM studies. Choosing the correct gastric reference sensor is crucial for accurate test results and avoiding misdiagnosis. Standardization of reference sensor selection or supportive testing for uncertain results should be considered.
Integrated relaxation pressure (IRP) calculation is the gold standard for LES relaxation but dependent on a single, arbitrarily selected gastric reference sensor, resulting in variable diagnoses in greater than one quarter of esophageal manometry studies. Standardization of reference sensor selection is needed for consistent and reproducible IRP measurements.
Background
Whether patients with defecatory disorders (DDs) with favorable response to a footstool have distinctive anorectal pressure characteristics is unknown. We aimed to identify the clinical ...phenotype and anorectal pressure profile of patients with DDs who benefit from a footstool.
Methods
This is a retrospective review of patients with high resolution anorectal manometry (HR‐ARM) and balloon expulsion test (BET) from a tertiary referral center. BET was repeated with a 7‐inch‐high footstool in those who failed it after 120 s. Data were compared among groups with respect to BET results.
Key Results
Of the 667 patients with DDs, a total of 251 (38%) had failed BET. A footstool corrected BET in 41 (16%) of those with failed BET. Gender‐specific differences were noted in anorectal pressures, among patients with and without normal BET, revealing gender‐based nuances in pathophysiology of DDs. Comparing patients who passed BET with footstool with those who did not, the presence of optimal stool consistency, with reduced instances of loose stools and decreased reliance on laxatives were significant. Additionally, in women who benefited from a footstool, lower anal pressures at rest and simulated defecation were observed. Independent factors associated with a successful BET with a footstool in women included age <50, Bristol 3 or 4 stool consistency, lower anal resting pressure and higher rectoanal pressure gradient.
Conclusion & Inferences
Identification of distinctive clinical and anorectal phenotype of patients who benefited from a footstool could provide insight into the factors influencing the efficacy of footstool utilization and allow for an individualized treatment approach in patients with DDs.
This is a retrospective review of patients with defecatory disorders (DDs) from a tertiary referral center that identifies clinical characteristics and anorectal pressure phenotypes of patients with DDs that achieve successful rectal balloon expulsion only with a footstool.
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 TH2 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.
Eosinophilic esophagitis (EoE) is a clinicopathologic disease characterized by symptoms of esophageal dysfunction and esophageal eosinophilia. The underlying pathophysiology involves an antigen‐mediated TH2 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.
In this work, we find that CD8
T cells expressing inhibitory killer cell immunoglobulin-like receptors (KIRs) are the human equivalent of Ly49
CD8
regulatory T cells in mice and are increased in the ...blood and inflamed tissues of patients with a variety of autoimmune diseases. Moreover, these CD8
T cells efficiently eliminated pathogenic gliadin-specific CD4
T cells from the leukocytes of celiac disease patients in vitro. We also find elevated levels of KIR
CD8
T cells, but not CD4
regulatory T cells, in COVID-19 patients, correlating with disease severity and vasculitis. Selective ablation of Ly49
CD8
T cells in virus-infected mice led to autoimmunity after infection. Our results indicate that in both species, these regulatory CD8
T cells act specifically to suppress pathogenic T cells in autoimmune and infectious diseases.
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