Parth J. Parekh

The Influence of the Gut Microbiome on Obesity, Metabolic Syndrome and Gastrointestinal Disease

There is a fine balance in the mutual relationship between the intestinal microbiota and its mammalian host. It is thought that disruptions in this fine balance contribute/account for the pathogenesis of many diseases. Recently, the significance of the relationship between gut microbiota and its mammalian host in the pathogenesis of obesity and the metabolic syndrome has been demonstrated. Emerging data has linked intestinal dysbiosis to several gastrointestinal diseases including inflammatory bowel disease, irritable bowel syndrome, nonalcoholic fatty liver disease, and gastrointestinal malignancy. This article is intended to review the role of gut microbiota maintenance/alterations of gut microbiota as a significant factor as a significant factor discriminating between health and common diseases. Based on current available data, the role of microbial manipulation in disease management remains to be further defined and a focus for further clinical investigation.

Sleep Disorders and Inflammatory Disease Activity: Chicken or the Egg?

Sleep dysfunction is a highly prevalent condition that has long been implicated in accelerating disease states characterized by having an inflammatory component such as systemic lupus erythematosus, HIV, and multiple sclerosis. Inflammatory bowel disease (IBD) is a chronic, debilitating disease that is characterized by waxing and waning symptoms, which are a direct result of increased circulating inflammatory cytokines. Recent studies have demonstrated sleep dysfunction and the disruption of the circadian rhythm to result in an upregulation of inflammatory cytokines. Not only does this pose a potential trigger for disease flares but also an increased risk of malignancy in this subset of patients. This begs to question whether or not there is a therapeutic role of sleep cycle and circadian rhythm optimization in the prevention of IBD flares. Further research is needed to clarify the role of sleep dysfunction and alterations of the circadian rhythm in modifying disease activity and also in reducing the risk of malignancy in patients suffering from IBD.

New Anticoagulants and Antiplatelet Agents: A Primer for the Clinical Gastroenterologist

The discovery of the first oral anticoagulant, warfarin, was a milestone in anticoagulation. Warfarins well-known limitations, however, have led to the recent development of more effective anticoagulants. The rapidly growing list of these drugs, however, presents a challenge to endoscopists who must treat patients on these sundry medications. This review is intended to summarize the pharmacological highlights of new anticoagulants, with particular attention to suggested “best-practice” recommendations for the withholding of these drugs before endoscopic procedures.

Ammonia and Its Role in the Pathogenesis of Hepatic Encephalopathy

Hepatic encephalopathy (HE) is a commonly encountered sequela of chronic liver disease and cirrhosis with significant associated morbidity and mortality. Although ammonia is implicated in the pathogenesis of HE, the exact underlying mechanisms still remain poorly understood. Its role in the urea cycle, astrocyte swelling, and glutamine and gamma-amino-n-butyric acid systems suggests that the pathogenesis is multifaceted. Greater understanding in its underlying mechanism may offer more targeted therapeutic options in the future, and thus further research is necessary to fully understand the pathogenesis of HE.

Endoscopic ultrasound-guided liver biopsy

Liver biopsy remains the cornerstone in the diagnosis and management of liver disorders. Results of liver biopsy can often drive therapeutic decision-making. Unfortunately, studies have shown conventional biopsy techniques to carry significant sampling variability that can potentially impact patient care. Endoscopic ultrasound (EUS) is gaining traction as an alternative method of biopsy. For parenchymal disease, it can decrease sampling variability. It offers a more targeted approach for focal lesions. Its diagnostic yield and limited adverse event profile make it a promising approach for liver biopsy.

The Role of Gut Microflora and the Cholinergic Anti-inflammatory Neuroendocrine System in Diabetes Mellitus

The obesity epidemic has drastically impacted the state of health care in the United States. Paralleling this epidemic is the incidence of diabetes mellitus, with a notable shift toward a much younger age of onset. While central to the pathogenesis of diabetes associated with obesity is the role of inflammation attributed to “adiposopathy.” Emerging data suggest that changes in sympathetic/parasympathetic balance regulated by the brain precede changes in the inflammatory cascade. It has now been established that the gut microflora contributes significantly to the activation and inhibition of autonomic control and impact the set of the neuroinflammatory inhibitory reflex mediated by the cholinergic nervous system. There has been a paradigm shift toward further investigating commensal bacteria in the pathogenesis of obesity and diabetes mellitus and its complications, as dysbiosis is thought to play a pivotal role in diabetic-associated disorders. This paper is intended to evaluate the role of intestinal dysbiosis in the pathogenesis of diabetes mellitus and examine the potential for restoration of balance via use of probiotics.

Dexlansoprazole: delayed-release orally disintegrating tablets for the treatment of heartburn associated with non-erosive gastroesophageal reflux disease and the maintenance of erosive esophagitis

ABSTRACT Introduction: Gastroesophageal reflux disease (GERD) is a common condition afflicting millions of patients, whose prevalence continues to rise owing to the aging population and increasing burden of comorbid conditions, such as obesity. Currently, the mainstay of therapy for GERD is treatment with proton pump inhibitors (PPIs), which have proven efficacy, safety, and tolerability. Despite this, a considerable number of patients have refractory symptoms to PPI therapy. Dexlansoprazole is a new addition to the class of PPIs, which has a unique dual delayed drug release system, which aims to address the current limitations of acid suppressive therapy by offering extended acid suppression and improved ease of administration. Areas covered: This manuscript covers the pharmacokinetics, pharmacodynamics, clinical efficacy, and regulatory approval of dexlansoprazole. Additionally, there is further discussion concerning the current market settings and the potential future impact of dexlansoprazole. Expert commentary: Overall, dexlansoprazole offers benefits in its ease of administration and proven efficacy in the healing, maintenance of erosive esophagitis, and symptomatic non-erosive GERD. Long-term, dexlansoprazole will likely find a niche market among patients who fail other acid suppressive therapy or who desire simplified administration for compliance concerns, but will likely come at a higher out of pocket expense than comparable generic PPIs.

Diagnosis of Lynch syndrome before colorectal resection: does it matter?

Lynch syndrome (LS), also known as hereditary nonpolyposis colorectal cancer (HNPCC), is an autosomal dominant genetic condition which predisposes patients to several different types of cancer, most notably colorectal cancer [1]. LS can be implicated in up to 5 % of colorectal cancers (CRC), making it the most common form of hereditary CRC [2]. However, in patients with early-onset CRC this number can be up to 17 % [3]. There has been an increased focus on early-onset CRC in general due to recently demonstrated rising CRC incidence rates in this group, although the underlying pathogenic factors are not completely understood [4]. Timing of LS diagnosis in suspected patients is critical, as early identification can facilitate management decisions regarding surgical intervention, colonoscopic surveillance and screening for extracolonic cancers. In addition, expedited germline genetic testing can be offered to at-risk family members. Recent guidelines suggest that all newly diagnosed CRCs, regardless of patient age, can be considered for evaluation for mismatch repair deficiency by microsatellite instability (MSI) and/or immunohistochemistry (IHC) testing for mismatch repair proteins [5]. Germline genetic testing can follow in order to confirm LS and assess for specific underlying mutations. When surgery is indicated, the aforementioned testing should ideally occur preoperatively so that results can assist planning and decision making in the operating room [5]. Due to high rates of metachronous CRC in LS patients undergoing partial colon resections (16 % at 10 years, 41 % at 20 years and 62 % at 30 years), even in those undergoing colonoscopic surveillance, colectomy with ileorectal anastomosis is recommended [5, 6]. Studies have demonstrated the rate of metachronous lesions to drop significantly (postoperative risk is 0–3.4 %) when the recommended surgical intervention was performed [6, 7]. Given this expanding appreciation for the role that genetic analysis may play in CRC surgical and medical management, the expectations would be for a rise in genetic evaluation, unfortunately the reality seems far from it. A recent study utilizing CDC comparative effectiveness research data conducted by our group evaluated the frequency of MSI and IHC testing in early-onset CRC patients and availability of testing results preoperatively [8]. The study, which was the first population-based study in the USA to evaluate LS screening practices, took place in Louisiana, which was recently demonstrated to have one of the highest incidence rates of CRC in the USA and very high rates of early-onset CRC, particularly in certain regions [9]. Data collected from the Louisiana Tumor Registry totaling 274 patients statewide B50 years of age and diagnosed with CRC in 2011 were analyzed. They found that in this young, high-risk population in which LS screening rates would be expected to be the highest, MSI and/or IHC testing was performed in only 23 % of patients with abnormalities found in 21.7 % of cases. Additionally, of those with abnormal IHC staining patterns, results were suggestive of LS in 87.5 % of cases highlighting the highrisk nature of the early-onset CRC population. Lastly, they found that these results were available preoperatively only 16.9 % of the time due to testing being ordered infrequently on preoperative colonoscopy specimens or results & J. J. Karlitz jkarlitz@tulane.edu

Current Strategies to Reduce Gastrointestinal Bleeding Risk Associated with Antiplatelet Agents.

AbstractAntiplatelet agents remain the cornerstone in the primary and secondary therapeutic intervention for cardiovascular disease. Some patients may be subjected to a year or more of dual antiplatelet therapy to reduce the risk of subsequent cardiovascular events. Patients on antiplatelet therapy have an increased risk of gastrointestinal bleeding; however, not all patients benefit from concomitant acid suppressive therapy. This review will provide an overview of the pharmacology of antiplatelet agents and outline patient risk profiles that ought to be considered when considering prophylactic therapy to reduce gastrointestinal toxicity. In addition, we discuss the current risk-reduction strategies intended to mitigate against the potential for related gastroduodenal injury.

Bowel Preparation for Colonoscopy

Abstract Although colonoscopy is recognized as the “gold standard” for current colon cancer screening testing, the quality of the exam is critically dependent on a high-level colon-cleansing preparation. This chapter will highlight the current pharmacologic and procedural advances in attaining a high-quality preparation as well as the scoring systems to assess adequacy of cleansing.