The Logistical Backbone of Photoreceptor Cell Function: Complementary Mechanisms of Dietary Vitamin A Receptors and Rhodopsin Transporters.

In this review, we outline our current understanding of the mechanisms involved in the absorption, storage, and transport of dietary vitamin A to the eye, and the trafficking of rhodopsin protein to the photoreceptor outer segments, which encompasses the logistical backbone required for photoreceptor cell function. Two key mechanisms of this process are emphasized in this manuscript: ocular and systemic vitamin A membrane transporters, and rhodopsin transporters. Understanding the complementary mechanisms responsible for the generation and proper transport of the retinylidene protein to the photoreceptor outer segment will eventually shed light on the importance of genes encoded by these proteins, and their relationship on normal visual function and in the pathophysiology of retinal degenerative diseases.

Constipated patients with functional defecatory disorder have secondary rectal hyposensitivity due to altered rectal biomechanics.

BACKGROUND AND AIM: Rectal hyposensitivity (RH) is common in constipation and often coexists with functional defecatory disorder (FDD). Rectal sensory thresholds are routinely evaluated with the anorectal manometry probe; however, the gold standard for the assessment of rectal sensitivity is with a barostat, use of which is limited by time constraints and availability. A novel rapid barostat bag (RBB) may facilitate measurements of rectal sensitivity. The aim is to evaluate the relationship between RH (measured by the RBB) and FDD (defined as any minor disorder of rectoanal coordination by the London classification) in constipated patients. METHODS: Consecutive constipated patients referred for anorectal function testing underwent anorectal manometry with the 3D-HDAM probe as well as rectal sensation testing with the RBB pump. RH was defined by volume to first sensation >30%, urge to defecate >80%, or discomfort >100% (normalized to rectal capacity). RESULTS: Fifty-three percent of constipated patients had RH. Patients with FDD had a significantly increased volume to first sensation (134.5 mL vs 102.0, P = 0.02), urge to defecate (187.0 mL vs 149.0, P = 0.04), and rectal capacity (253.5 mL vs 209.0, P = 0.04) compared to constipated patients without FDD. There was no difference in normalized sensory thresholds (percent of rectal capacity) nor the prevalence of hyposensitivity to each sensory threshold nor overall hyposensitivity. CONCLUSION: Patients with FDD, when measured with the RBB, have increased sensory thresholds on volumetric distension, but RH was not observed when sensory threshold volume were normalized to rectal capacity. This may reflect "secondary" RH due to altered rectal biomechanics.

Esophageal motility in systemic sclerosis before and after autologous hematopoietic cell transplantation.

INTRODUCTION: Systemic sclerosis (SSc) is associated with esophageal dysmotility. Autologous hematopoietic cell transplantation (HCT) results in improvement of skin tightness and lung function. Whether esophageal motility improves after HCT is unknown. METHODS: Esophageal motility was studied using high-resolution esophageal manometry in 21 SSc patients before and at multiple time points after autologous HCT. Median posttransplant follow-up was 2 years (range, 6 months to 5 years). RESULTS: Prior to HCT, all 21 patients had abnormal motility-10 (48%) had unmeasurable and 11 (52%) had measurable peristalsis. Manometric diagnosis in the former 10 patients was "absent contractility" and in the latter 11 patients "ineffective esophageal motility (IEM)." After HCT, among the 10 patients with absent contractility, 9 continued to have absent contractility and one demonstrated weak measurable peristalsis. Of the 11 patients with IEM, 5 experienced SSc relapse, and 2 out of these 5 patients developed absent contractility. Among the 6 non-relapsed patients, 4 continued to have IEM, and 2 developed normal motility. CONCLUSIONS: HCT appears to have no beneficial effect on motility in patients with unmeasurable peristalsis. In patients with measurable peristalsis, HCT appears to stabilize and in some normalize motility, unless relapse occurs. Key Points • In patients with systemic sclerosis, esophageal dysmotility is a significant contributor to morbidity and so far, there has been no data describing the effects of hematopoietic cell transplantation on esophageal motility. • Our work demonstrated that in patients with systemic sclerosis and unmeasurable esophageal peristalsis prehematopoietic cell transplantation, there was no measurable beneficial effect of transplantation on esophageal motility. • In patients with systemic sclerosis and measurable peristalsis prehematopoietic cell transplantation, esophageal motility stabilized, except in relapsed patients.

Manometric parameters, when measured with the 3-dimensional high-definition anorectal manometry probe, poorly predict prolonged balloon expulsion time.

BACKGROUND: There are little data evaluating the performance of the 3-dimensional high-definition anorectal manometry (3D-HDAM) system in the diagnosis of dyssynergic defecation. Physical properties of the thicker, rigid, 3D-HDAM probe may have implications on the measurements of anorectal pressures. AIM: Our aim was to compare 3D-HDAM to balloon expulsion test and magnetic resonance (MR) defecography. METHODS: Consecutive constipated patients referred for anorectal function testing at the Calgary Gut Motility Centre (Calgary, Canada) between 2014 and 2019 were assessed. All patients underwent anorectal manometry with the 3D-HDAM probe, and a subset underwent BET or MR defecography. Anorectal manometric variables were compared between patients who had normal and abnormal BET. RESULTS: Over the study period, 81 patients underwent both 3D-HDAM and BET for symptoms of constipation. 52 patients expelled the balloon within 3 minutes. Patients with abnormal BET had significantly lower rectoanal pressure differential (RAPD) (-61 vs. -31 mmHg for normal BET, p = 0.03) and defecation index (0.29 vs. 0.56, p = 0.03). On logistic regression analysis, RAPD (OR: 0.99, 95% CI: 0.97-0.99, p = 0.03) remained a negative predictor of abnormal BET. On ROC analysis, RAPD had an AUC of 0.65. There was good agreement between dyssynergic patterns on 3D-HDAM and defecographic evidence of dyssynergia (sensitivity 80%, specificity 90%, PLR 9, NLR 0.22, accuracy 85%). CONCLUSIONS: Manometric parameters, when measured with the 3D-HDAM probe, poorly predict prolonged balloon expulsion time. RAPD remains the best predictor of prolonged balloon expulsion time. The 3D-HDAM probe may not be the ideal tool to diagnose functional defecatory disorders.

Anticholinergic, anti-depressant and other medication use is associated with clinically relevant oesophageal manometric abnormalities.

BACKGROUND: Medications can affect gastrointestinal tract motility. However, their effects on oesophageal motility in particular are often not as widely known or may be underestimated. AIM: To review the effect of existing medication use on high-resolution oesophageal manometry (HRM) in a 'real-world' setting. METHODS: Adult patients with upper gut symptoms and normal endoscopy or imaging who had HRM over a 22-month period were analysed. Achalasia and major disorders of peristalsis were excluded. All medications taken within 24 hours of the procedure were prospectively recorded and compared with HRM results, controlling for age, gender and proton pump inhibitor use. RESULTS: A total of 502 patients (323 female, mean age 51) were recruited. Of these, 41.2% had normal oesophageal HRM, while 41.4% had ineffective oesophageal motility (IOM) and 7.6% had oesophagogastric junction outflow obstruction (OGJOO). Serotonin/norepinephrine reuptake inhibitors (SNRI) and opioids were associated with significantly higher resting lower oesophageal sphincter pressure. Benzodiazepines and opioids were associated with elevated integrated relaxation pressure. SNRI and inhaled beta-agonists were associated with increased distal contractile index, whereas calcium channel blockers were associated with a lower distal contractile index. Odds ratio of being on anticholinergics was higher in IOM patients vs normal (3.6, CI 1.2-10.8). Odds ratio for anticholinergics, inhaled beta-agonists, anticonvulsants, SNRIs and opioids (trend) were all > 3 for OGJOO patients vs normal. CONCLUSION: Many medication classes are associated with abnormal HRM variables and diagnoses such as OGJOO and IOM; some of these associations are probably causal. These possible links should be taken into consideration during manometry interpretation.

Gastroesophageal Reflux Disease Is Not Associated With Jackhammer Esophagus: A Case-control Study.

BACKGROUND/AIMS: The pathophysiology of jackhammer esophagus (JE) remains unknown but may be related to gastroesophageal reflux disease or medication use. We aim to determine if pathologic acid exposure or the use of specific classes of medications (based on the mechanism of action) is associated with JE. METHODS: High-resolution manometry (HRM) studies from November 2013 to March 2019 with a diagnosis of JE were identified and compared to symptomatic control patients with normal HRM. Esophageal acid exposure and medication use were compared between groups. Multivariate regression analysis was performed to look for predictors of mean distal contractile integral. RESULTS: Forty-two JE and 127 control patients were included in the study. Twenty-two (52%) JE and 82 (65%) control patients underwent both HRM and ambulatory pH monitoring. Two (9%) JE patients and 14 (17%) of controls had evidence of abnormal acid exposure (DeMeester score > 14.7); this difference was not significant (P = 0.290). Thirty-six (86%) JE and 127 (100%) control patients had complete medication lists. Significantly more JE patients were on long-acting beta agonists (LABA) (JE = 5, control = 4; P = 0.026) and calcium channel blockers (CCB) (JE = 5, control = 3; P = 0.014). Regular opioids (ß = 0.298, P = 0.042), CCB (ß = 0.308, P = 0.035), and inhaled anticholinergics (ß = 0.361, P = 0.049) predicted mean distal contractile integral (R2 = 0.082, F = 4.8; P = 0.003). CONCLUSIONS: Pathologic acid exposure does not appear to be associated with JE. JE patients had increased CCB and LABA use. The unexpected finding of increased LABA use warrants more investigation and may provide support for a cholinergic etiology of JE.

Esophagogastric junction outflow obstruction on manometry: Outcomes and lack of benefit from CT and EUS.

BACKGROUND: Esophagogastric junction outflow obstruction (EGJOO) is a manometric diagnosis based on the Chicago Classification defined by inadequate relaxation of the gastroesophageal junction (GEJ) with swallowing, but with sufficient peristalsis such that the criteria for achalasia are not met. Possible causes include anatomical and functional etiologies. Further investigations, including computed tomography (CT) of the chest and endoscopic ultrasound (EUS), to help elucidate the etiology of EGJOO have been suggested, but the utility of this approach has not been proven. METHODS: All new diagnoses of EGJOO made in the calendar years 2015-2016 were included. A review was performed for each patient to assess clinical outcomes, diagnostic, and therapeutic interventions after the EGJOO diagnosis. KEY RESULTS: 107 EGJOO patients were included. Their primary complaints were dysphagia (68%), chest pain (12%), reflux (8%), pre-operative assessment (6%), regurgitation (3%), and cough (3%). The mean IRP was 21.8 mm Hg. After a mean follow-up period of 463 days, the etiology of EGJOO remained undetermined in 67% of patients. 48% of patients were investigated with cross-sectional imaging (and 10% with EUS to rule out external compression or malignancy as a cause of EGJOO; none of these tests provided any further useful information). In only two cases did the EGJOO progress to achalasia. CONCLUSIONS & INFERENCES: EGJOO is a manometric diagnosis with unclear clinical significance and outcome. CT and EUS of the GEJ were unhelpful at determining the cause of this entity. In this series, very few appear to progress to achalasia, none were due to malignancy, and many resolved spontaneously.

The impact of hepatitis B knowledge and stigma on screening in Canadian Chinese persons.

BACKGROUND: Chronic hepatitis B (CHB) infection is endemic in East Asia, and those who emigrate to North America have higher rates of CHB infection when compared with the general population. To date, Chinese persons residing in Canada have not been mandated to be screened for CHB infection. OBJECTIVE: To understand factors that influence hepatitis B screening behaviour among the Chinese community in Toronto, Ontario, and to determine whether stigma acts as a barrier to screening. METHODS: Self-identified Chinese individuals at a family physician's office and at English as a second language (ESL) classes in Toronto completed a questionnaire with demographic questions, a hepatitis B virus (HBV) stigma scale and an HBV knowledge scale. Pearson product moment correlation and multiple regression techniques were used to analyze the data. RESULTS: The study group included 343 individuals. Their mean (± SD) age was 48.76 ± 17.49 years and the majority were born in China (n=229 [68%]). The mean score on the HBV knowledge scale was 10.13 ± 1.76 (range 0 to 15), with higher scores indicating greater HBV knowledge. The mean score on the stigma scale was 54.60 ± 14.18 (range 20 to 100), with higher scores indicating more stigma. Being an immigrant, having a family physician and having greater knowledge of HBV were associated with increased rates of screening for this infection. In contrast, greater levels of HBV stigma were associated with decreased likelihood of screening for HBV infection. CONCLUSIONS: HBV stigma is associated with reduced rates of screening for this infection.