Bone marrow oxalosis with pancytopenia in a patient with short bowel syndrome: Report of a case and review of the literature.

Systemic oxalosis is a condition in which calcium oxalate crystals deposit into various bodily tissues. Although this may occur as the result of a rare primary syndrome in which an error of glyoxylate metabolism causes an overproduction of oxalate, it is more often seen as a secondary process characterized by increased enteric oxalate absorption. Here, we describe a patient with short bowel syndrome on long-term parenteral nutrition support who developed a unique manifestation of systemic oxalosis, leading to deposition of oxalate crystals within the bone marrow contributing to pancytopenia. In this report, in addition to reviewing the literature on this presumably rare manifestation of oxalosis, we also discuss its pathogenesis in the setting of short bowel syndrome and its management, including prevention.

Temporospatial shifts in the human gut microbiome and metabolome after gastric bypass surgery.

Although the etiology of obesity is not well-understood, genetic, environmental, and microbiome elements are recognized as contributors to this rising pandemic. It is well documented that Roux-en-Y gastric bypass (RYGB) surgery drastically alters the fecal microbiome, but data are sparse on temporal and spatial microbiome and metabolome changes, especially in human populations. We characterized the structure and function (through metabolites) of the microbial communities in the gut lumen and structure of microbial communities on mucosal surfaces in nine morbidly obese individuals before, 6 months, and 12 months after RYGB surgery. Moreover, using a comprehensive multi-omic approach, we compared this longitudinal cohort to a previously studied cross-sectional cohort (n = 24). In addition to the expected weight reduction and improvement in obesity-related comorbidities after RYGB surgery, we observed that the impact of surgery was much greater on fecal communities in comparison to mucosal ones. The changes in the fecal microbiome were linked to increased concentrations of branched-chain fatty acids and an overall decrease in secondary bile acid concentrations. The microbiome and metabolome data sets for this longitudinal cohort strengthen our understanding of the persistent impact of RYGB on the gut microbiome and its metabolism. Our findings highlight the importance of changes in mucosal and fecal microbiomes after RYGB surgery. The spatial modifications in the microbiome after RYGB surgery corresponded to persistent changes in fecal fermentation and bile acid metabolism, both of which are associated with improved metabolic outcomes.

Efficacy of Fecal Microbiota Transplantation for Recurrent C. Difficile Infection in Inflammatory Bowel Disease.

BACKGROUND: Clostridioides difficile infection (CDI) is associated with poor outcomes in inflammatory bowel disease (IBD) patients. Data are scarce on efficacy of fecal microbiota transplant (FMT) for recurrent CDI in IBD patients. METHODS: We reviewed health records of IBD patients (18 years of age or older) with recurrent CDI who underwent FMT. Outcomes of FMT for CDI were assessed on the basis of symptoms and stool test results. RESULTS: We included 145 patients (75 women [51.7%]; median age, 46 years). Median IBD duration was 8 (range, 0-47) years, 36.6% had Crohn disease, 61.4% had ulcerative colitis, and 2.1% had indeterminate colitis. Median number of prior CDI episodes was 3 (range, 3-20), and 61.4% had received vancomycin taper. Diarrhea resolved after FMT in 48 patients (33.1%) without further testing. Ninety-five patients (65.5%) underwent CDI testing owing to post-FMT recurrent diarrhea; 29 (20.0%) had positive results. After FMT, 2 patients received empiric treatment of recurrent CDI without symptom resolution, suggesting IBD was the cause of symptoms. The overall cure rate of CDI after FMT was 80.0%, without CDI recurrence at median follow-up of 9.3 (range, 0.1-51) months. Forty-three patients (29.7%) had planned IBD therapy escalation after CDI resolution; none de-escalated or discontinued IBD therapy. Overall, 7.6% had worsening IBD symptoms after FMT that were treated as new IBD flares. No clinical predictors of FMT failure were identified. CONCLUSIONS: Few patients had new IBD flare after FMT. Fecal microbiota transplantation effectively treats recurrent CDI in IBD patients but has no apparent beneficial effect on the IBD course.

Postural Tachycardia Syndrome (POTS) and the GI Tract: A Primer for the Gastroenterologist.

Postural tachycardia syndrome (POTS) is one of the most common causes of orthostatic intolerance and is being increasingly recognized in clinical practice. Gastrointestinal (GI) symptoms are reported commonly in patients with POTS and pose a considerable management challenge, making it imperative that gastroenterologists be aware of this condition and its GI comorbidities. Although the evidence presented herein does not prove causation, it does support an association between GI symptoms, GI dysmotility, and POTS. At present, the evaluation and treatment of GI symptoms in patients with POTS remains largely empirical. General measures to treat POTS may lead to improvement in both GI and non-GI symptoms. GI symptoms refractory to these measures should prompt further diagnostic evaluation of gastrointestinal dysmotility and appropriate dietary and pharmacologic management. This review focuses its attention on the involvement of the GI tract in POTS including a discussion of GI symptoms and conditions associated with POTS, followed by an analysis of abnormalities in gut physiology described in POTS, and concluding with an overview of management and suggestions for research directions.

Proceedings of the 2017 ASPEN Research Workshop-Gastric Bypass: Role of the Gut.

The goal of the National Institutes of Health-funded American Society for Parenteral and Enteral Nutrition 2017 research workshop (RW) "Gastric Bypass: Role of the Gut" was to focus on the exciting research evaluating gut-derived signals in modulating outcomes after bariatric surgery. Although gastric bypass surgery has undoubted positive effects, the mechanistic basis of improved outcomes cannot be solely explained by caloric restriction. Emerging data suggest that bile acid metabolic pathways, luminal contents, energy balance, gut mucosal integrity, as well as the gut microbiota are significantly modulated after bariatric surgery and may be responsible for the variable outcomes, each of which was rigorously evaluated. The RW served as a timely and novel academic meeting that brought together clinicians and researchers across the scientific spectrum, fostering a unique venue for interdisciplinary collaboration among investigators. It promoted engaging discussion and evolution of new research hypotheses and ideas, driving the development of novel ameliorative, therapeutic, and nonsurgical interventions targeting obesity and its comorbidities. Importantly, a critical evaluation of the current knowledge regarding gut-modulated signaling after bariatric surgery, potential pitfalls, and lacunae were thoroughly addressed.

Distinctive microbiomes and metabolites linked with weight loss after gastric bypass, but not gastric banding.

Roux-en-Y gastric bypass (RYGB) and laparoscopic adjustable gastric banding (LAGB) are anatomically different bariatric operations. RYGB achieves greater weight loss compared with LAGB. Changes in the gut microbiome have been documented after RYGB, but not LAGB, and the microbial contribution to sustainable surgical weight loss warrants further evaluation. We hypothesized that RYGB imposes greater changes on the microbiota and its metabolism than LAGB, and that the altered microbiota may contribute to greater weight loss. Using multi-omic approaches, we analyzed fecal microbial community structure and metabolites of pre-bariatric surgery morbidly obese (PreB-Ob), normal weight (NW), post-RYGB, and post-LAGB participants. RYGB microbiomes were significantly different from those from NW, LAGB and PreB-Ob. Microbiome differences between RYGB and PreB-Ob populations were mirrored in their metabolomes. Diversity was higher in RYGB compared with LAGB, possibly because of an increase in the abundance of facultative anaerobic, bile-tolerant and acid-sensible microorganisms in the former. Possibly because of lower gastric acid exposure, phylotypes from the oral cavity, such as Escherichia, Veillonella and Streptococcus, were in greater abundance in the RYGB group, and their abundances positively correlated with percent excess weight loss. Many of these post-RYGB microorganisms are capable of amino-acid fermentation. Amino-acid and carbohydrate fermentation products-isovalerate, isobutyrate, butyrate and propionate-were prevalent in RYGB participants, but not in LAGB participants. RYGB resulted in greater alteration of the gut microbiome and metabolome than LAGB, and RYGB group exhibited unique microbiome composed of many amino-acid fermenters, compared with nonsurgical controls.

Nutrient deficiencies prior to bariatric surgery.

PURPOSE OF REVIEW: The purpose of this review is to provide an update of recent additions to our understanding of the prevalence of nutrient deficiencies and the potential role of preoperative weight loss in contributing to these deficiencies in obese individuals planning to undergo bariatric surgery. RECENT FINDINGS: Recent reports that have included bariatric surgery candidates from sites around the world have shown consistent deficiencies in a variety of nutrients. Although protein-energy malnutrition is uncommon preoperatively, micronutrient deficiencies occur commonly with multiple deficiencies often present in the same individual. No difference in the prevalence of deficiency between men and women is apparent, and a standard profile of susceptibility to deficiency has not been identified. In the only studies that have evaluated dietary intake of total energy, macronutrients and micronutrients preoperatively, despite an excess of calories ingested, micronutrient intake tends to be lower than recommended. SUMMARY: A high prevalence of micronutrient deficiencies, especially vitamin D, folate, B12 and iron, is present in obese individuals being considered for bariatric surgery. Despite high-caloric intake, the deficiencies present appear to be related to the poor quality of the diet and low micronutrient intake. These findings strengthen prior recommendations of routine preoperative nutritional screening. Because a standard profile of susceptibility to deficiency has not been identified, extensive nutritional screening, including micronutrient testing, should be considered in all patients in the preoperative setting. Finally, we recommend early supplementation of vitamins and minerals based on laboratory assessment and incorporation of a program to optimize eating behaviors prior to surgery.

ACG Clinical Guideline: Nutrition Therapy in the Adult Hospitalized Patient.

The value of nutrition therapy for the adult hospitalized patient is derived from the outcome benefits achieved by the delivery of early enteral feeding. Nutritional assessment should identify those patients at high nutritional risk, determined by both disease severity and nutritional status. For such patients if they are unable to maintain volitional intake, enteral access should be attained and enteral nutrition (EN) initiated within 24-48 h of admission. Orogastric or nasogastric feeding is most appropriate when starting EN, switching to post-pyloric or deep jejunal feeding only in those patients who are intolerant of gastric feeds or at high risk for aspiration. Percutaneous access should be used for those patients anticipated to require EN for >4 weeks. Patients receiving EN should be monitored for risk of aspiration, tolerance, and adequacy of feeding (determined by percent of goal calories and protein delivered). Intentional permissive underfeeding (and even trophic feeding) is appropriate temporarily for certain subsets of hospitalized patients. Although a standard polymeric formula should be used routinely in most patients, an immune-modulating formula (with arginine and fish oil) should be reserved for patients who have had major surgery in a surgical ICU setting. Adequacy of nutrition therapy is enhanced by establishing nurse-driven enteral feeding protocols, increasing delivery by volume-based or top-down feeding strategies, minimizing interruptions, and eliminating the practice of gastric residual volumes. Parenteral nutrition should be used in patients at high nutritional risk when EN is not feasible or after the first week of hospitalization if EN is not sufficient. Because of their knowledge base and skill set, the gastroenterologist endoscopist is an asset to the Nutrition Support Team and should participate in providing optimal nutrition therapy to the hospitalized adult patient.

Short bowel syndrome and small bowel transplantation.

PURPOSE OF REVIEW: 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 FINDINGS: 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. SUMMARY: 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.

Role of the gastroenterologist in managing obesity.

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.

Fecal microbiota transplant for recurrent Clostridium difficile infection: Mayo Clinic in Arizona experience.

OBJECTIVE: To report the initial experience of treating recurrent Clostridium difficile infection (CDI) with fecal microbiota transplant (FMT) at Mayo Clinic in Arizona. PATIENTS AND METHODS: 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. RESULTS: 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. CONCLUSION: A standardized regimen of FMT for recurrent CDI is safe, is highly effective, and can be provided using a relatively simple protocol.

Quick fix or long-term cure? Pros and cons of bariatric surgery.

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.

Paraneoplastic gastrointestinal dysmotility: when to consider and how to diagnose.

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.

Nutrition and metabolic complications after bariatric surgery and their treatment.

The increase in the number of bariatric procedures annually suggests that these patients will constitute an increasing portion of obese patients who require hospital and intensive care. Currently, little prospective information is available regarding the course of bariatric surgery patients requiring intensive care. Knowledge of the type of bariatric operation performed and an understanding of its anatomy and physiology are useful to provide optimal care to these patients, particularly when considering potential nutrition complications and their diagnosis and treatment. In this article, the authors describe nutrition problems that may be present and potentially affect the course of a hospitalized and/or critically ill patient who has previously undergone a bariatric operation.

Use of an electromagnetic colonoscope to assess maneuvers associated with cecal intubation.

BACKGROUND: Safe and effective colonoscopy is aided by the use of endoscopic techniques and maneuvers (ETM) during the examination including patient repositioning, stiffening of the endoscope and abdominal pressure. AIM: To better understand the use and value of ETM during colonoscopy by using a device that allows real-time imaging of the colonoscope insertion shaft. METHODS: The use of ETM during colonoscopy and their success was recorded. Experienced colonoscopists and endoscopy assistants used a commercially available electromagnetic (EM) transmitter and a special adult variable stiffness instrument with 12 embedded sensors to examine 46 patients. In 5 of these a special EM probe passed through the instrument channel of a standard pediatric variable stiffness colonoscope was used instead of the EM colonoscope. RESULTS: Thirty-nine men and 7 women with a mean age of 64 years (range 33-90) were studied. The cecum was intubated in 93.5% (43/46). The mean time to reach the cecum was 10.6 minutes (range 3-25). ETM were used a total of 174 times in 41 of the patients to assist with cecal intubation. When ETM were required to reach the cecum, and the cecum was intubated, an average of 3.82 ETM/patient was used. While ETM were used most often when the tip of the colonoscope was in the left side of the colon (rectum 5.0%, sigmoid colon 20.7%, descending colon 5.0%, and splenic flexure 11.6%), when the instrument was in the transverse colon (14.8%), hepatic flexure (20.7%) and ascending colon (19.8%) the use of ETM was also required. When the colonoscope tip was in the transverse colon, hepatic flexure and ascending colon, ETM success rates were less (61.1%, 52.0%, and 41.7% respectively) compared to the left colon success rates (rectum 83.3%, sigmoid colon 84.0%, descending colon 100%, and splenic flexure 85.7%). CONCLUSION: The EM colonoscope allows imaging of the insertion shaft without fluoroscopy and is a useful device for evaluating the efficacy of ETM. ETM are important tools of the colonoscopist and are used most often in the left colon where they are most effective.

Obesity is associated with increased 48-h esophageal acid exposure in patients with symptomatic gastroesophageal reflux.

OBJECTIVES: Obesity has been associated with gastroesophageal reflux disease (GERD) but the relationship between body mass index (BMI) and esophageal acid exposure remains poorly understood. We hypothesized that overweight (OW) and obese (OB) patients with GER symptoms would have a higher degree of esophageal acid exposure than with normal weight (NW) patients. METHODS: 157 patients separated in groups according to BMI were studied for 48h while off antisecretory medications using ambulatory wireless capsule pH-metry. The pH capsule was appropriately positioned and esophageal pH data were collected. Appropriate univariate and multivariate statistical methods were used. RESULTS: Groups did not differ in age, but more women were in the NW group. OB patients had a fivefold increase in odds for abnormal total acid exposure compared with NW (OR=5.01; 95% CI 2.94, 12.95). Total acid exposure time (AET) was elevated in OB (8.7%+/-5.1%) compared with NW (5.3%+/-5.2%; P<0.05). AET was highest during awake, upright periods. The DeMeester score was higher in OB (31.7+/-19.2) and OW (26.0+/-16.8) groups compared with the NW (19.8+/-17.6) group (P<0.001). AET increased from day 1 to day 2 in the OB group only. CONCLUSIONS: This is the first study to report a positive relationship between BMI and esophageal acid exposure time using prolonged, continuous wireless esophageal pH-metry. Abnormal AET was more frequent in OB patients. Variability in AET increased from day 1 to day 2 in the OB group, supporting the use of more prolonged pH studies in subsets of patients.

Human gut microbiota in obesity and after gastric bypass.

Recent evidence suggests that the microbial community in the human intestine may play an important role in the pathogenesis of obesity. We examined 184,094 sequences of microbial 16S rRNA genes from PCR amplicons by using the 454 pyrosequencing technology to compare the microbial community structures of 9 individuals, 3 in each of the categories of normal weight, morbidly obese, and post-gastric-bypass surgery. Phylogenetic analysis demonstrated that although the Bacteria in the human intestinal community were highly diverse, they fell mainly into 6 bacterial divisions that had distinct differences in the 3 study groups. Specifically, Firmicutes were dominant in normal-weight and obese individuals but significantly decreased in post-gastric-bypass individuals, who had a proportional increase of Gammaproteobacteria. Numbers of the H(2)-producing Prevotellaceae were highly enriched in the obese individuals. Unlike the highly diverse Bacteria, the Archaea comprised mainly members of the order Methanobacteriales, which are H(2)-oxidizing methanogens. Using real-time PCR, we detected significantly higher numbers of H(2)-utilizing methanogenic Archaea in obese individuals than in normal-weight or post-gastric-bypass individuals. The coexistence of H(2)-producing bacteria with relatively high numbers of H(2)-utilizing methanogenic Archaea in the gastrointestinal tract of obese individuals leads to the hypothesis that interspecies H(2) transfer between bacterial and archaeal species is an important mechanism for increasing energy uptake by the human large intestine in obese persons. The large bacterial population shift seen in the post-gastric-bypass individuals may reflect the double impact of the gut alteration caused by the surgical procedure and the consequent changes in food ingestion and digestion.

Prevalence and impact of musculoskeletal injury among endoscopists: a controlled pilot study.

BACKGROUND: Endoscopy-associated musculoskeletal injury has not been well studied. Our aim was to identify the frequency and significance of musculoskeletal injury among gastroenterologists compared with a similar group of nonprocedure-oriented internal medicine specialists and subspecialists. METHODS: An electronic survey was developed and administered to all gastroenterologists and hepatologists [gastroenterologists (GI) group] and a sampling of nonprocedure-oriented internal medicine specialists and subspecialists (non-GI group) employed by Mayo Clinic. The questionnaire assessed several areas including current or past pain injury associated with performing endoscopy, location and description of pain or injury, impact of pain or injury, and prevention strategies. A modified survey was sent to the control group. RESULTS: The response rate was 63% in the GI group and 45% in the non-GI group. The 2 groups were of similar age and level of physical activity. The frequency of musculoskeletal injury was higher in the GI group (74% vs. 35%; P<0.001). The most common sites of injury among the GI group were the thumb (19%), low back (19%), hand (17%), and neck (10%). There was no significant association between volume of endoscopy or years performing endoscopy and injury. Most of the GI group made modifications in their endoscopic practice to reduce injury risk. CONCLUSIONS: Musculoskeletal injury occurs more commonly among gastroenterologists than nonprocedure-oriented internal medicine specialists. Most reported minor injuries, but members of the GI group tended to have more severe repercussions relating to ability to work. More attention to injury prevention is needed among gastroenterologists.