The Impact of Chronic Cannabis Use on Esophageal Motility in Patients Referred for Esophageal Manometry.

BACKGROUND: Tetrahydrocannabinol, the main psychoactive compound in cannabis, binds with high affinity to the cannabinoid 1 receptor. Small randomized controlled studies using conventional manometry have shown that the cannabinoid 1 receptor can modulate esophageal function, namely transient lower esophageal sphincter relaxation frequency and lower esophageal sphincter tone. The effect of cannabinoids on esophageal motility in patients referred for esophageal manometry has not been fully elucidated using high-resolution esophageal manometry (HREM). We aimed to characterize the clinical effect of chronic cannabis use on esophageal motility utilizing HREM. METHODS: Patients who underwent HREM from 2009 to 2019 were identified at 4 academic medical centers. The study group consisted of patients with a noted history of chronic cannabis use, a diagnosis of cannabis-related disorder, or a positive urine toxicology screen. Age and gender-matched patients with no history of cannabis use were selected to form the control group. Data on HREM metrics based on the Chicago classification V3, and the prevalence of esophageal motility disorders were compared. Confounding effects of BMI and medications on esophageal motility were adjusted for. RESULTS: Chronic cannabis use was found to be an independent negative predictor of weak swallows (ß=-8.02, P =0.0109), but not a predictor of failed swallows ( P =0.6890). The prevalence of ineffective esophageal motility was significantly lower in chronic cannabis users compared with nonusers (OR=0.44, 95% CI 0.19-0.93, P =0.0384). There was no significant difference in the prevalence of other esophageal motility disorders between the 2 cohorts. In patients with dysphagia as their primary indication for HREM, chronic cannabis use was found to be independently associated with increased median integrated relaxation pressure (ß=6.638, P =0.0153) and increased mean lower esophageal sphincter resting pressure (ß=10.38, P =0.0084). CONCLUSIONS: Chronic cannabis use is associated with decreased weak swallows and reduced prevalence of ineffective esophageal motility in patients referred for esophageal manometry. In patients referred for dysphagia, chronic cannabis use is associated with increased integrated relaxation pressure and lower esophageal sphincter resting pressure, though not to levels above the normal range.

Sorting out the Relationship between Gastroesophageal Reflux Disease and Sleep.

PURPOSE OF REVIEW: Gastroesophageal reflux disease is one of the most common conditions encountered by primary care physicians, gastroenterologists, foregut surgeons and otolaryngologists. While approximately 50% of patients experience nocturnal reflux symptoms, the relationship between gastroesophageal reflux disease and sleep is often overlooked. The aim of this review is to provide an update on the current understanding of this relationship and its clinical implications. Recent studies pertaining to the association between GERD and sleep with focus on sleep disturbances, obstructive sleep apnea, extraesophageal manifestations of GERD and treatment are discussed. RECENT FINDINGS: There is a close relationship between GERD and sleep disturbances, but the nature of this relationship remains to be elucidated. Similarly, new data supports the association between GERD and obstructive sleep apnea, but whether this association is independent of confounding risk factors remains unresolved. Extraesophageal manifestations due to nocturnal GERD are primarily respiratory and can be explained by microaspiration and vagally-induced bronchospasm. Treatment of nocturnal GERD, both pharmacologically and surgically, improves sleep quality. Conversely, pharmacologic treatment of sleep disorders can improve nocturnal GERD symptoms. There is a bi-directional relationship between GERD and sleep. GERD is associated with various sleep disturbances. Sleep deficiency can exacerbate GERD. There is an association between extraesophageal manifestations and nocturnal GERD. Treatment directed towards GERD can improve sleep experience, and treatment directed to improve sleep can improve GERD symptoms.

Enhanced catalytic activity through the tuning of micropore environment and supercritical CO2 processing: Al(porphyrin)-based porous organic polymers for the degradation of a nerve agent simulant.

An Al(porphyrin) functionalized with a large axial ligand was incorporated into a porous organic polymer (POP) using a cobalt-catalyzed acetylene trimerization strategy. Removal of the axial ligand afforded a microporous POP that is catalytically active in the methanolysis of a nerve agent simulant. Supercritical CO2 processing of the POP dramatically increased the pore size and volume, allowing for significantly higher catalytic activities.

Aortic Aneurysm Presenting As Deglutition Syncope.

Deglutitive syncope is defined as a neurally mediated syncope in which loss of consciousness occurs during or immediately after swallowing. The causes of deglutitive syncope vary widely and range from intraluminal causes, as well as extra-esophageal compression. In this case report, we present a rare case of deglutitive syncope caused by a thoracic aortic aneurysm compressing the proximal esophagus, a clinical entity described in the literature as dysphagia aortica.

Multiple Sclerosis Is Associated With Achalasia and Diffuse Esophageal Spasm.

Background/Aims: Multiple sclerosis (MS) is an inflammatory disease characterized by the demyelination of primarily the central nervous system. Diffuse esophageal spasm (DES) and achalasia are both disorders of esophageal peristalsis which cause clinical symptoms of dysphagia. Mechanisms involving dysfunction of the pre- and post-ganglionic nerve fibers of the myenteric plexus have been proposed. We sought to determine whether MS confers an increased risk of developing achalasia or DES. Methods: Cohort analysis was done using the Explorys database. Univariate logistic regression was performed to determine the odds MS confers to each motility disorder studied. Comparison of proportions of dysautonomia comorbidities was performed among the cohorts. Patients with a prior diagnosis of diabetes mellitus, chronic Chagas' disease, opioid use, or CREST syndrome were excluded from the study. Results: Odds of MS patients developing achalasia or DES were (OR, 2.09; 95% CI, 1.73-2.52; P < 0.001) and (OR, 3.15; 95% CI, 2.89-3.42; P < 0.001), respectively. In the MS/achalasia cohort, 27.27%, 18.18%, 9.09%, and 45.45% patients had urinary incontinence, gastroparesis, impotence, and insomnia, respectively. In the MS/DES cohort, 35.19%, 11.11%, 3.70%, and 55.56% had these symptoms. In MS patients without motility disorders, 12.64%, 0.79%, 2.21%, and 21.85% had these symptoms. Conclusions: Patients with MS have higher odds of developing achalasia or DES compared to patients without MS. MS patients with achalasia or DES have higher rates of dysautonomia comorbidities. This suggests that these patients have a more severe disease phenotype in regards to the extent of neuronal degradation and demyelination causing the autonomic dysfunction.

Memory-inspired spiking hyperdimensional network for robust online learning.

Recently, brain-inspired computing models have shown great potential to outperform today's deep learning solutions in terms of robustness and energy efficiency. Particularly, Spiking Neural Networks (SNNs) and HyperDimensional Computing (HDC) have shown promising results in enabling efficient and robust cognitive learning. Despite the success, these two brain-inspired models have different strengths. While SNN mimics the physical properties of the human brain, HDC models the brain on a more abstract and functional level. Their design philosophies demonstrate complementary patterns that motivate their combination. With the help of the classical psychological model on memory, we propose SpikeHD, the first framework that fundamentally combines Spiking neural network and hyperdimensional computing. SpikeHD generates a scalable and strong cognitive learning system that better mimics brain functionality. SpikeHD exploits spiking neural networks to extract low-level features by preserving the spatial and temporal correlation of raw event-based spike data. Then, it utilizes HDC to operate over SNN output by mapping the signal into high-dimensional space, learning the abstract information, and classifying the data. Our extensive evaluation on a set of benchmark classification problems shows that SpikeHD provides the following benefit compared to SNN architecture: (1) significantly enhance learning capability by exploiting two-stage information processing, (2) enables substantial robustness to noise and failure, and (3) reduces the network size and required parameters to learn complex information.

EventHD: Robust and efficient hyperdimensional learning with neuromorphic sensor.

Brain-inspired computing models have shown great potential to outperform today's deep learning solutions in terms of robustness and energy efficiency. Particularly, Hyper-Dimensional Computing (HDC) has shown promising results in enabling efficient and robust cognitive learning. In this study, we exploit HDC as an alternative computational model that mimics important brain functionalities toward high-efficiency and noise-tolerant neuromorphic computing. We present EventHD, an end-to-end learning framework based on HDC for robust, efficient learning from neuromorphic sensors. We first introduce a spatial and temporal encoding scheme to map event-based neuromorphic data into high-dimensional space. Then, we leverage HDC mathematics to support learning and cognitive tasks over encoded data, such as information association and memorization. EventHD also provides a notion of confidence for each prediction, thus enabling self-learning from unlabeled data. We evaluate EventHD efficiency over data collected from Dynamic Vision Sensor (DVS) sensors. Our results indicate that EventHD can provide online learning and cognitive support while operating over raw DVS data without using the costly preprocessing step. In terms of efficiency, EventHD provides 14.2× faster and 19.8× higher energy efficiency than state-of-the-art learning algorithms while improving the computational robustness by 5.9×.

Incidence and Risk of Various Types of Arterial Thromboembolism in Patients With Cancer.

OBJECTIVE: To describe the temporal association and identify risk factors between cancer diagnosis and various types of arterial thromboembolism (ATE). PATIENTS AND METHODS: We inquired an aggregated electronic health record database (Explorys, IBM Corp., Armonk, New York) and identified patients with cancer from January 1999 to October 2019, with various types of ATE, including myocardial infarction, acute ischemic stroke, acute limb ischemia, acute mesenteric ischemia, acute renal infarction, and retinal artery occlusion. We investigated the temporal relationship between cancer diagnosis and ATE events by examining the incidence ratio (IR) of ATE before and after diagnosis of cancer. RESULTS: We identified 305,384 patients with cancer and ATE. The 30-day interval IR of total ATE was elevated shortly before and after cancer diagnosis, which was consistent among different ATE and cancer types. The incidence was highest within a 330-day window (90 days before and 240 days after cancer diagnosis), and IR peaked at 13.9 (95% confidence interval [CI], 13.6 to 14.2) in the first 30 days following diagnosis of cancer. Compared with patients with cancer who never developed ATE, patients with ATE had more cardiovascular risk factors at baseline. Patients with brain cancer, lung cancer, colorectal cancer, and pancreatic cancer had the highest risk of developing ATE, whereas ATE type was anatomically associated with cancer type. CONCLUSION: In this observational study of an aggregated US patient population, those with newly diagnosed cancer had increased risk of ATE events. This risk was most elevated in a 330-day window around cancer diagnosis and was consistent across different types of ATE and cancer.

No association between chronic use of ranitidine, compared with omeprazole or famotidine, and gastrointestinal malignancies.

BACKGROUND: In 2019, the United States Food and Drug Administration detected above-regulation levels of the human carcinogen N-nitrosodimethylamine (NDMA) in ranitidine, resulting in a complete removal of the medication from the market. NDMA is known to cause gastrointestinal malignancies in animal models. AIM: To determine if patients who were receiving ranitidine have a higher risk of developing cancers of the digestive tract compared to patients taking other anti-reflux medications. METHODS: Using the nationwide database IBM Explorys, patients taking ranitidine were compared to patients on either famotidine or omeprazole. Incidence data of new malignancies of the oesophagus, stomach, liver, pancreas, and colon/rectum were obtained in 1-year intervals for up to 10 years. Two multivariable logistic regression models were used to calculate odds ratios (ORs), one adjusting for common risk factors for each cancer studied, and the other for demographic factors. RESULTS: Patients on ranitidine who were compared to patients on famotidine had ORs of 0.51(95% CI 0.43-0.60), 0.43(95% CI 0.36-0.51), 0.39(95% CI 0.36-0.41), 0.54(95% CI 0.49-0.62), and 0.46(95% CI 0.43-0.49) of developing oesophageal, gastric, hepatocellular, pancreatic, and colorectal cancers, respectively (P < 0.001). Patients on ranitidine compared to omeprazole had ORs of 0.62(95% CI 0.52-0.72), 0.58(95% CI 0.49-0.68), 0.81 (95% CI 0.76-0.86), 0.68(95% CI 0.60-0.76), and 0.66(95% CI 0.62-0.70) of developing oesophageal, gastric, hepatocellular, pancreatic, and colorectal cancers respectively (P < 0.001). CONCLUSIONS: Use of ranitidine was not associated with an increased odds of developing gastrointestinal malignancies compared to omeprazole or famotidine use.

Risk of thromboembolism in patients with multiple myeloma treated with daratumumab: a systemic review and meta-analysis.

BACKGROUND: Patients with multiple myeloma (MM) have increased risks of venous thromboembolism (VTE) and arterial thromboembolism (ATE). The risk of thrombosis differs among different treatment regimens. It is unknown if daratumumab could affect thrombosis risk. METHODS: A comprehensive search was conducted until April 2020. Events of VTE, including pulmonary embolism and deep venous thrombosis, as well as events of ATE, including acute ischemic stroke and myocardial infarction, were extracted from trials. In addition, events of thrombocytopenia and gastrointestinal (GI) bleeding were also extracted. RESULTS: Six trials were included in the meta-analysis. Daratumumab was associated with a lower risk of VTE compared with non-daratumumab regimen (Risk ratio [RR], 0.60; 95% confidence interval [CI], 0.40-0.91). The risk of ATE had no significant difference (RR, 0.80; 95% CI, 0.48-1.33). Daratumumab was also associated with a trend of higher risk of Grade 3/4 thrombocytopenia (RR, 1.14; 95% CI, 0.94-1.38), while the risk of GI bleeding was not significantly different (RR, 1.32; 95% CI, 0.38-4.65). CONCLUSION: Daratumumab is associated with lower risk of VTE in clinical trials.

Proton-pump inhibitor use and the development of new ischemic heart disease in non-cardiac chest pain patients.

BACKGROUND: The growing reports regarding cardiac-related adverse events of chronic proton-pump inhibitors (PPI) treatment, a mainstay therapy of non-cardiac chest pain (NCCP), have raised concerns about alteration of the natural course in NCCP patients using PPI. We aimed to determine if NCCP patients receiving PPI have a higher risk of developing ischemic heart disease (IHD) compared to those not receiving PPI therapy. METHODS: Three groups of NCCP patients were included; PPI, histamine-2 receptor antagonist (H2RA), and no antireflux treatment. Diagnosis of NCCP had to precede diagnosis of IHD by at least 30 days, and in those receiving antireflux treatment at 30 days after starting the medication. Data analysis was corrected for 6 known confounding factors for IHD including hyperlipidemia, hypertension, obesity, smoking status, male gender, and diabetes mellitus. KEY RESULTS: Of the patients on PPI or H2RA, 1280 and 250, respectively, developed IHD. Patients on PPI therapy displayed an increased odd of developing ischemic heart disease compared to patients never placed on therapy (OR 1.14, 95% CI 1.03-1.25, P-value .0093). Patients placed on H2RA therapy did not show a statistically significant change in risk compared to patients who were not placed on therapy (OR 0.90, 95% CI 0.77-1.06, P-value .2049). Number needed to harm in the PPI and H2RA groups was 17 and 45, respectively. CONCLUSIONS: PPIs confer a statistically significant, but marginal effect on the risk of IHD development in NCCP patients. Thus, PPI use in NCCP only minimally alters the overall benign natural course of the disease.