[Show abstract][Hide abstract] ABSTRACT: Functional dysphagia (FD) is characterized by the presence of dysphagia without evidence of mechanical esophageal obstruction, GERD, and histopathology-based esophageal motor disorders. Dysphagia is common in older patients; however, there is a paucity of information regarding the type and frequency of peristaltic abnormalities compared to younger patients. Based on recently validated criteria for classification of weak peristalsis using high-resolution manometry (HRM), we hypothesized that older patients with FD would have more peristaltic defects detected by HRM compared to younger FD patients. A retrospective review of our motility database yielded 65 patients that met inclusion criteria. Patients were divided into two groups based on age (younger: <70 years; older: ≥70 years). Patients were interviewed, completed a quality-of-life questionnaire, and underwent solid-state HRM. The two groups differed in age but in no other demographic characteristics, severity of dysphagia, or quality of life. Dyspeptic symptoms, including nausea (p < 0.001), early satiety (p = 0.01), bloating (p = 0.02), and belching (p = 0.01), were also more prevalent in younger FD patients. Older age was associated with weak peristalsis involving frequent failed peristalsis, small proximal peristaltic defects (2-5 cm), and large proximal peristaltic defects (>5 cm) (p < 0.001). The mean contraction amplitude was also lower in the older group (p < 0.05). These data support the hypothesis that older patients with FD have a higher frequency of peristaltic abnormalities on HRM compared to younger patients. Older age was associated with increased frequency of weak peristalsis with small and large peristaltic defects.
[Show abstract][Hide abstract] ABSTRACT: The purpose of this review is to provide an update of recent advances in the areas of short bowel syndrome (SBS) and small bowel transplantation (SBT).
Recent reports from two of the largest multicenter randomized, controlled trials in patients with SBS support the safety and efficacy of teduglutide as an aid to parenteral nutrition weaning. In well selected SBS patients, outcomes as diverse as survival, macronutrient absorption and parenteral nutrition weaning are improved after autologous gastrointestinal reconstructive surgery. SBT is no longer considered investigational and given improved outcomes noted in recent reports, indications for transplantation are expanding. Although SBT early survival rates are approaching those of other organ allografts, long-term graft survival remains suboptimal.
Recently available trophic factors hold promise as aids in restoring freedom from parenteral nutrition support; however, their long-term benefits, preferred timing of administration in relation to the onset of SBS, optimal patient selection for use, duration of treatment and cost effectiveness require further study. Despite recent evidence of improved early survival after SBT, more dedicated research is needed to design more effective strategies to better tolerize small bowel grafts, prevent rejection and, ultimately, improve long-term outcomes. Reserved for well selected patients, autologous gastrointestinal reconstruction should be considered complementary and not antagonistic to SBT.
Current opinion in gastroenterology 01/2014; · 4.33 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: The role of the gut microbiome in arresting pathogen colonization and growth is important for protection against Clostridium difficile infection (CDI). Observational studies associate proton pump inhibitor (PPI) use and CDI incidence. We hypothesized that PPI use affected the distal gut microbiome over time, an effect that would be best explored by time-longitudinal study of healthy subjects on PPI in comparison to treatment-naïve CDI subjects. This study enrolled nine healthy human subjects and five subjects with treatment-naïve CDI. After random assignment to a low (20 mg/day) or high (2× 20 mg/day) dose group, fecal samples were collected from the nine healthy subjects before, during, and after 28 days of PPI use. This was done in conjunction with pre-treatment fecal collection from CDI subjects. High-throughput sequencing (16S rRNA) was performed on time-longitudinal samples to assess changes to the healthy gut microbiome associated with prolonged PPI usage. The healthy samples were then compared to the CDI subjects to explore changes over time to the gut microbiome associated with PPI use and potentially related to CDI.
We report that PPI usage at low and high dosages, administered for 28 days, resulted in decreases to observed operational taxonomic unit (OTU) counts after both 1 week and 1 month. This decrease resulted in observed OTU levels that were similar to those found in treatment-naïve CDI patients, which was partly reversible after a 1 month recovery period. We did not detect a dose-dependent difference in OTU levels nor did we detect significant changes in taxa previously reported to be affected by PPI treatment.
While our observation of diminishing observed OTU counts during PPI therapy is a preliminary finding in a small cohort, our hypothesis that PPIs disrupt the healthy human gut microbiome is supported in this group. We conclude that decreases in observed species counts were reversible after cessation of PPI usage within 1 month. This finding may be a potential explanation for the association between prolonged PPI usage and CDI incidence.
[Show abstract][Hide abstract] ABSTRACT: In recent years, fecal microbiota transplantation (aka fecal transplantation, fecal bacteriotherapy, FMT) has become increasing utilized to treat recurrent and refractory Clostridium difficile infection (CDI). Almost 600,000 cases of CDI occur each year in the United States. Of these, an estimated 15,000 patients have a recurrence. The management of recurrent disease has been challenging for patients and clinicians. Increasingly, FMT has been recognized as an effective option for these patients. This article explores why FMT has reemerged as a practical therapeutic modality. In the process, the logistics by which the procedure is performed and the factors that may affect quality, safety, and patient outcomes will be described.
Nutrition in Clinical Practice 08/2013; · 2.06 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: To report the initial experience of treating recurrent Clostridium difficile infection (CDI) with fecal microbiota transplant (FMT) at Mayo Clinic in Arizona.
The study retrospectively reviewed FMTs performed at Mayo Clinic in Arizona between January 1, 2011, and January 31, 2013. All the recipients had multiple recurrent CDIs unresponsive to traditional antibiotic drug therapy. A standardized protocol was developed to identify patients, screen donors, perform FMT, and determine outcomes via telephone surveys.
Thirty-one patients (mean ± SD age, 61.26±19.34 years) underwent FMT. Median time from index infection to FMT was 340 days. Ninety-seven percent (29 of 30) of patients reported substantial improvement or resolution of diarrhea (median time to improvement, 3 days), 74% (17 of 23) reported improvement or resolution of abdominal pain (median time to improvement, 3 days), and 55% (16 of 29) had improvement or resolution of fatigue (median time to improvement, 6 days). Three patients underwent repeated FMT owing to persistent symptoms; 2 reported improvement in diarrhea with the second therapy. No serious adverse events directly related to FMT were reported.
A standardized regimen of FMT for recurrent CDI is safe, is highly effective, and can be provided using a relatively simple protocol.
Mayo Clinic Proceedings 08/2013; 88(8):799-805. · 5.79 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Obesity has become a major public health problem as a consequence of its prevalence, negative impact on morbidity, mortality and quality of life and its associated direct and indirect healthcare costs. The etiology of obesity is multifactorial and reflects complex interactions of genetic, neurohumoral, environmental, behavioral and possibly, microbial factors. Available treatments for obesity include diet and exercise, behavioral modification, medications and surgery. Gastroenterologists are becoming increasingly involved in the care of obese patients. Although much of this care has historically centered on the preoperative and postoperative care of the bariatric patient, gastroenterologists are also evaluating and managing a variety of gastrointestinal symptoms and disorders that occur more commonly among obese individuals and are increasingly involved in the primary treatment of obesity. In this review, the gastrointestinal symptoms and disorders that are associated with obesity will be reviewed, the gastrointestinal contribution to the pathogenesis of obesity will be described and the current treatment options of obesity and where the gastroenterologist typically plays a role in the management will be discussed.
Expert review of gastroenterology & hepatology 07/2013; 7(5):439-51.
[Show abstract][Hide abstract] ABSTRACT: Malnutrition commonly complicates the course of patients with cirrhosis and has a multifactorial etiology. Despite the important role that nutrition plays in the prognosis of those with cirrhosis, the nutrition assessment process can be challenging in this setting. A number of tools are available to aid in the nutrition assessment of the cirrhotic patient; however, none are without limitations. Although the assessment process can be difficult, the ability to properly manage the nutrient needs of the patient presents an additional set of challenges because of the catabolic nature of the disease process and common occurrence of anorexia and other symptoms leading to poor oral intake. In this review, the nutrition assessment tools and general guidelines for nutrition management in patients with advanced liver disease are discussed to promote recognition of the nutrition issues affecting this patient population and lead to their improved survival and reduced morbidity.
Nutrition in Clinical Practice 02/2013; 28(1):15-29. · 2.06 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: The past decade has seen an enormous increase in the number of bariatric, or weight loss, operations performed. This trend is likely to continue, mirroring the epidemic of obesity around the world and its rising prevalence among children. Bariatric surgery is considered by many to be the most effective treatment for obesity in terms of maintenance of long-term weight loss and improvement in obesity-related comorbid conditions. Although overly simplified, the primary mechanisms of the surgical interventions currently utilized to treat obesity are the creation of a restrictive or malabsorptive bowel anatomy. Operations based on these mechanisms include the laparoscopic adjustable gastric band and laparoscopic vertical sleeve gastrectomy (considered primarily restrictive operations), the laparoscopic biliopancreatic diversion with or without a duodenal switch (primarily malabsorptive operation), and the laparoscopic Roux-en-Y gastric bypass (considered a combination restrictive and selective malabsorptive procedure). Each operation has pros and cons. Important considerations, for the patient and surgeon alike, in the decision to proceed with bariatric surgery include the technical aspects of the operation, postoperative complications including long-term nutritional problems, magnitude of initial and sustained weight loss desired, and correction of obesity-related comorbidities. Herein, the pros and cons of the contemporary laparoscopic bariatric operations are reviewed and ongoing controversies relating to bariatric surgery are discussed: appropriate patient selection, appropriate operation selection for an individual patient, surgeon selection, and how to measure success after surgery.
[Show abstract][Hide abstract] ABSTRACT: Energy balance is an equilibrium between the amount of energy extracted from the diet and the amount expended. Selective pressures throughout evolution have programmed animals to protect energy stores through the accumulation of adipose tissue; as diets have changed and energy-dense foods have become readily available, obesity rather than malnutrition has become the primary concern in developed nations. Nevertheless, factors other than the types of food and their availability appear to be important. Recent evidence suggests that the gut microbiota play a role in energy harvest, storage, and expenditure. The preponderance of the evidence demonstrates that germ-free mice are protected against obesity and that the transfer of gut microbes from conventionally raised animals results in dramatic increases in body fat content and insulin resistance. Moreover, the composition of the gut microbiota has been shown to differ in lean and obese humans and animals and to change rapidly in response to dietary factors. The gut microbiota may also influence the development of conditions characterized by low-level inflammation, such as obesity and type 2 diabetes, through systemic exposure to bacterial lipopolysaccharide derived from the intestinal microbiota. Together, these data suggest that modification of the gut microbiota may be a relevant therapeutic avenue for obesity and other metabolic disorders.
The American Journal of Gastroenterology Supplements. 07/2012; 1(1):22-27.
[Show abstract][Hide abstract] ABSTRACT: Functional dyspepsia (FD), a common functional gastrointestinal disorder, is defined by the Rome III criteria as symptoms of epigastric pain or discomfort (prevalence in FD of 89-90%), postprandial fullness (75-88%), and early satiety (50-82%) within the last 3 months with symptom onset at least 6 months earlier. Patients cannot have any evidence of structural disease to explain symptoms and predominant symptoms of gastroesophageal reflux are exclusionary. Symptoms of FD are non-specific and the pathophysiology is diverse, which explains in part why a universally effective treatment for FD remains elusive.
To present current management options for the treatment of FD (therapeutic gain/response rate noted when available).
The utility of Helicobacter pylori eradication for the treatment of FD is modest (6-14% therapeutic gain), while the therapeutic efficacy of proton pump inhibitors (PPI) (7-10% therapeutic gain), histamine-type-2-receptor antagonists (8-35% therapeutic gain), prokinetic agents (18-45%), tricyclic antidepressants (TCA) (response rates of 64-70%), serotonin reuptake inhibitors (no better than placebo) is limited and hampered by inadequate data. This review discusses dietary interventions and analyses studies involving complementary and alternative medications, and psychological therapies.
A reasonable treatment approach based on current evidence is to initiate therapy with a daily PPI in H. pylori-negative FD patients. If symptoms persist, a therapeutic trial with a tricyclic antidepressant may be initiated. If symptoms continue, the clinician can possibly initiate therapy with an anti-nociceptive agent, a prokinetic agent, or some form of complementary and alternative medications, although evidence from prospective studies to support this approach is limited.
[Show abstract][Hide abstract] ABSTRACT: Malnutrition may manifest as either obesity or undernutrition. Accumulating evidence suggests that the gut microbiota plays an important role in the harvest, storage, and expenditure of energy obtained from the diet. The composition of the gut microbiota has been shown to differ between lean and obese humans and mice; however, the specific roles that individual gut microbes play in energy harvest remain uncertain. The gut microbiota may also influence the development of conditions characterized by chronic low-level inflammation, such as obesity, through systemic exposure to bacterial lipopolysaccharide derived from the gut microbiota. In this review, the role of the gut microbiota in energy harvest and fat storage is explored, as well as differences in the microbiota in obesity and undernutrition.
Nutrition in Clinical Practice 02/2012; 27(2):201-14. · 2.06 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Small intestinal bacterial overgrowth (SIBO) occurs due to alteration of the microbiota within the upper gastrointestinal tract. Proton pump inhibitor (PPI) therapy has been suggested as a risk factor for SIBO; however, the published reports have yielded conflicting results on the association between PPI therapy and risk of developing SIBO. The aim of this study was to compare the prevalence of SIBO as measured by glucose hydrogen breath testing (GHBT) in patients on PPI therapy compared with those not on PPI therapy.
A retrospective chart review was completed for all patients who underwent GHBT testing from 2004 to 2010. Breath samples for hydrogen (H₂) and methane (CH₄) were collected before and every 20 min for 120 min following ingestion of a 50-g oral glucose load. We used the following criteria to define a positive GHBT (a) increase in H₂ > 20 parts per million (p.p.m.) over baseline, (b) sustained rise H₂ > 10 p.p.m. over baseline, (c) CH₄ > 15 p.p.m. over baseline, and (d) either rise H₂ > 20 p.p.m. over baseline or CH₄ > 15 p.p.m.
A total of 1,191 patients (70% female) were included, of whom 566 (48%) were on PPI therapy. GHBT positivity did not differ significantly between PPI users and nonusers by any of the diagnostic criteria used and PPI use was not significantly associated with GHBT positivity using any of these criteria. GHBT positivity was associated with older age (odds ratio (OR) 1.03, 95% confidence interval (CI) 1.01-1.04) and antidiarrheal use (OR 1.99, 95% CI 1.15-3.44) using H₂ > 20, older age (OR 1.01, 95% CI 1.00-1.02) and diarrhea (OR 1.53, 95% CI 1.13-2.09) using H₂ > 10, and older age (OR 1.01, 95% CI 1.00-1.02) using either H₂ > 20 or CH₄ > 15. PPI use was not significantly associated with GHBT positivity using any of these criteria.
In this large, adequately powered equivalence study, PPI use was not found to be significantly associated with the presence of SIBO as determined by the GHBT.
The American Journal of Gastroenterology 02/2012; 107(5):730-5. · 9.21 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: BACKGROUND: Functional dyspepsia (FD) is a common problem affecting up to 10-25% of individuals. FD accounts for significant health care costs and affects quality of life but has no definitive treatment. OBJECTIVES: The Functional Dyspepsia Treatment Trial (FDTT) aims to test whether treatment with an antidepressant (amitriptyline or escitalopram) leads to improvement of symptoms in patients with moderate to severe FD. DESIGN: The FDTT is an international multicenter, parallel group, randomized, double-blind, placebo-controlled trial to evaluate whether 12 weeks of treatment with escitalopram or amitriptyline improves FD symptoms compared to treatment with placebo. Secondly, it is hypothesized that acceleration of solid gastric emptying, reduction of postprandial satiation, and enhanced gastric volume change with a meal will be significant positive predictors of short- and long-term outcomes for those on antidepressants vs. placebo. The third aim is to examine whether polymorphisms of GNβ3 and serotonin reuptake transporter influence treatment outcomes in FD patients receiving a tricyclic antidepressant, selective serotonin reuptake inhibitor therapy, or placebo. METHODS: The FDTT enrollment began in 2006 and is scheduled to randomize 400 patients by the end of 2012 to receive an antidepressant or placebo for 12 weeks, with a 6-month post-treatment follow-up. The study incorporates multiple validated questionnaires, physiological testing, and specific genetic evaluations. The protocol was approved by participating centers' Institutional Review Boards and an independent Data Safety Monitoring Board was established for monitoring to ensure patient safety and a single interim review of the data in December 2010 (ClinicalTrials.gov number NCT00248651).
[Show abstract][Hide abstract] ABSTRACT: Subclassification of achalasia based on high-resolution manometry (HRM) may be clinically relevant because response to therapy may vary by subtype. However, the consistency and reliability of subtyping achalasia patients based on HRM remains undefined. The objectives of this study were to assess interrater and intrarater agreement (reliability) of achalasia subtyping using the Chicago classification, and to evaluate the diagnostic consistency between clinicians interpreting HRM.
After receiving training on the classification criteria, five raters classified 20 achalasia and 10 non-achalasia cases in separate sessions 1 week apart. To further assess agreement, two raters classified all 101 available achalasia HRMs. Agreement for the classification of subtypes of achalasia was calculated using Cohen's κ and Krippendorff's α-reliability estimate.
Estimates of agreement among raters was good during both sessions (α=0.75; 95% confidence interval=0.69, 0.81 and α=0.75; 95% confidence interval=0.68, 0.81). Both interrater (κ=0.86-1.0) and intrarater (κ=0.86-1.0) agreement were very good for type III achalasia. Agreement between types I and II was more variable. Reliability was improved when type I and type II were combined (α=0.84; 95% confidence interval=0.78, 0.89). When all available cases were classified by two experienced raters, agreement was very good (κ=0.81; 95% confidence interval=0.71, 0.91).
Interobserver and intraobserver agreement for differentiating achalasia from non-achalasia patients using HRM and the Chicago classification was very good to excellent. More variability was seen in agreement when classifying achalasia subtypes. The most variation was observed in classification between type I and type II achalasia, which have similar characteristics. Clearly, differentiating between panesophageal pressurization and compartmentalization should improve discrimination between these subtypes.
The American Journal of Gastroenterology 02/2012; 107(2):207-14. · 9.21 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: In this review of dysmotility in cancer patients, we have focused on paraneoplastic GI dysmotility as it provides an excellent example of how derangements of the neuromuscular apparatus of the gut can affect GI motility. A high index of clinical suspicion, together with serologic evaluation using a panel of autoantibodies in selected patients, is important in ensuring the early diagnosis of paraneoplastic GI dysmotility and may help guide management. Although it remains unproved that paraneoplastic antibodies are pathogenic, they are useful diagnostic markers. A better understanding of the pathogenesis of these disorders, including the role of paraneoplastic antibodies, will, hopefully, lead to earlier diagnosis and improved adjunctive, immunology-based treatments. Furthermore, even though successful treatment of the underlying cancer may not lead to reversal of the GI dysmotility, the recognition of a paraneoplastic syndrome may lead to early cancer diagnosis and a better chance of successful treatment of the cancer and overall survival. Although rare, it is imperative that clinicians be aware of the association between malignancy and GI dysmotility so that they know when to investigate for an underlying malignancy.
Gastroenterology clinics of North America 12/2011; 40(4):777-86. · 2.56 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: This report compiles the conclusions and recommendations for nutrition therapy of the obese, critically ill patient derived by the group of experts participating in this workshop on obesity in critical care nutrition. The recommendations are based on consensus opinions of the group after review of the current literature. Obesity clearly adds to the complexity of nutrition therapy in the intensive care unit (ICU). Obesity alters the incidence and severity of comorbidities, tolerance of the prescribed regimen, and ultimately patient outcome through the course of hospitalization. Although the basic principles of critical care nutrition apply to the obese ICU patient, a high-protein, hypocaloric regimen should be provided to reduce the fat mass, improve insulin sensitivity, and preserve lean body mass. The ideal enteral formula should have a low nonprotein calorie to nitrogen ratio and have a variety of pharmaconutrient agents added to modulate immune responses and reduce inflammation.
Journal of Parenteral and Enteral Nutrition 09/2011; 35(5 Suppl):88S-96S. · 3.14 Impact Factor