Shashank Garg

Microbiota Dynamics in Patients Treated with Fecal Microbiota Transplantation for Recurrent Clostridium difficile Infection

Clostridium difficile causes antibiotic-associated diarrhea and pseudomembraneous colitis and is responsible for a large and increasing fraction of hospital-acquired infections. Fecal microbiota transplantation (FMT) is an alternate treatment option for recurrent C. difficile infection (RCDI) refractory to antibiotic therapy. It has recently been discussed favorably in the clinical and scientific communities and is receiving increasing public attention. However, short- and long-term health consequences of FMT remain a concern, as the effects of the transplanted microbiota on the patient remain unknown. To shed light on microbial events associated with RCDI and treatment by FMT, we performed fecal microbiota analysis by 16S rRNA gene amplicon pyrosequencing of 14 pairs of healthy donors and RCDI patients treated successfully by FMT. Post-FMT patient and healthy donor samples collected up to one year after FMT were studied longitudinally, including one post-FMT patient with antibiotic-associated relapse three months after FMT. This analysis allowed us not only to confirm prior reports that RCDI is associated with reduced diversity and compositional changes in the fecal microbiota, but also to characterize previously undocumented post-FMT microbiota dynamics. Members of the Streptococcaceae, Enterococcaceae, or Enterobacteriaceae were significantly increased and putative butyrate producers, such as Lachnospiraceae and Ruminococcaceae were significantly reduced in samples from RCDI patients before FMT as compared to post-FMT patient and healthy donor samples. RCDI patient samples showed more case-specific variations than post-FMT patient and healthy donor samples. However, none of the bacterial groups were invariably associated with RCDI or successful treatment by FMT. Overall microbiota compositions in post-FMT patients, specifically abundances of the above-mentioned Firmicutes, continued to change for at least 16 weeks after FMT, suggesting that full microbiota recovery from RCDI may take much longer than expected based on the disappearance of diarrheal symptoms immediately after FMT.

Efficacy of Combined Jejunal and Colonic Fecal Microbiota Transplantation for Recurrent Clostridium difficile Infection

The prevalence of recurrent Clostridium difficile infection (RCDI) is increasing; fecal microbiota transplantation (FMT) is an effective therapy. However, there have been no studies of the efficacy of a single session of combined enteral and colonic FMT or characterizations of changes in the microbiota between donors and recipients. We performed a study of 27 patients with RCDI who were given a fixed volume of processed fecal filtrate via enteroscopy and colonoscopy in a single session. Patients were closely monitored, and fecal samples were collected from 2 patient-donor pairs for 16S rRNA analysis. All patients had reduced stool frequency, abdominal pain, white blood cell counts, and elimination of fecal C difficile toxin (P < .05). FMT increased microbial diversity, increasing proportions of Lachnospiraceae (phylum Firmicutes) and reducing proportions of Enterobacteriaceae. FMT was associated with marked changes in the composition of fecal microbiota in 2 patients with RCDI.

Efficacy of fecal microbiota transplantation in 2 children with recurrent Clostridium difficile infection and its impact on their growth and gut microbiome

ABSTRACT Fecal microbiota transplantation (FMT) is recognized as an alternative therapeutic modality for recurrent Clostridium difficile infection (RCDI); however, data on its efficacy in children are lacking, including its effect on their growth and fecal microbiota. We report on 2 young children (<3 years old) who failed available therapeutics for RCDI, but responded remarkably well to FMT. Besides resolution of clinical features of C difficile infection (CDI), FMT administration led to marked improvement in their growth, along with increased microbiota diversity, especially proportion of Bacteroides. Our 2 cases illustrate the efficacy of FMT in children with RCDI and its positive effect on their growth and gut microbiota.

Swallow syncope: clinical presentation, diagnostic criteria, and therapeutic options.

We recently encountered three patients with episodes of syncope associated with food ingestion. A 31-year-old woman had an episode of syncope in the hospital while drinking soda. Transient asystole was noted on the telemonitor, confirming the diagnosis of swallow syncope. The other two patients were 78- and 80 year old gentlemen, respectively, who presented with recurrent and transient episodes of dizziness during deglutition. Extensive work-up of syncope was negative in both cases and a diagnosis of swallow syncope was made by clinical criteria. These cases illustrate the challenging problem of swallow syncope. The diagnosis can be suspected on the basis of clinical presentation and confirmed with the demonstration of transient brady-arrhythmia during deglutition. Medical management includes avoiding trigger foods, use of anticholinergics, and/or placement of a permanent cardiac pacemaker.

Improved Bowel Preparation with Multimedia Education in a Predominantly African-American Population: A Randomized Study

Background and Aim. Inadequate bowel preparation is a major impediment in colonoscopy quality outcomes. Aim of this study was to evaluate the role of multimedia education (MME) in improving bowel preparation quality and adenoma detection rate. Methods. This was an IRB-approved prospective randomized study that enrolled 111 adult patients undergoing outpatient screening or surveillance colonoscopy. After receiving standard colonoscopy instructions, the patients were randomized into MME group (n = 48) and control group (n = 46). The MME group received comprehensive multimedia education including an audio-visual program, a visual aid, and a brochure. Demographics, quality of bowel preparation, and colonoscopy findings were recorded. Results. MME group had a significantly better bowel preparation in the entire colon (OR 2.65, 95% CI 1.16–6.09) and on the right side of the colon (OR 2.74, 95% CI 1.12–6.71) as compared to control group (p < 0.05). Large polyps (>1 cm) were found more frequently in the MME group (11/31, 35.5% versus 0/13; p < 0.05). More polyps and adenomas were detected in MME group (57 versus 39 and 31 versus 13, resp.) but the difference failed to reach statistical significance. Conclusion. MME can lead to significant improvement in the quality of bowel preparation and large adenoma detection in a predominantly African-American population.

A rare case of infectious colitis

BACKGROUND AND AIM Inflammatory bowel disease (IBD) is associated with an increased risk of colorectal cancer (CRC). Studies have shown tumorigenetic and histomorphological differences between IBD-associated CRC and non-IBD CRC, suggesting differences in tumor behavior and response to treatment. We aimed to compare tumor recurrence and survival rates following postoperative chemotherapy in CRC patients with and without IBD. METHODS Search of the Cleveland Clinics CRC database revealed 65 patients who had IBD-associated CRC and received postoperative adjuvant chemotherapy between 1994 and 2010. Twenty-one patients were excluded due to incomplete clinical data. Propensity score-matching based on age, surgery intent, CRC site, tumor grade, American Joint Committee on Cancer (AJCC) stage and T stage was used to match IBD and non-IBD patients (1:4). Competing risk and Cox regression models were used to analyze differences in disease-free survival and overall survival, respectively. RESULTS Forty-four patients with IBD-associated CRC were matched to 176 patients with non-IBD CRC. Among IBD patients, 29 (66%) had ulcerative colitis, 14 (32%) had Crohns disease, and one (2%) had indeterminate colitis. Mean IBD diagnosis age was 28.1 ± 14.5 years, and mean IBD duration at time of CRC treatment was 21.5 ± 12.6 years. Ten (23%) IBD patients had tumor recurrence compared with 34 (19%) non-IBD patients (P = .074). There was no significant difference in disease-free survival (hazard ratio [HR] = 0.60; 95% CI: 0.35-1.05; P = 0.074) or overall survival (HR = 0.87; 95% CI: 0.54-1.4; P = 0.58) between IBD and non-IBD patients. CONCLUSION Patients with IBD-associated CRC have comparable rates of tumor recurrence and survival following postoperative chemotherapy as CRC patients without IBD. Prospective studies are needed to confirm these findings and guide therapeutic decisions.Methicillin-resistant Staphylococcus aureus (MRSA) is responsible for numerous infectious processes. Gastrointestinal tract involvement is rather rare and only a handful of cases of MRSA colitis have been reported in North America. We present a case of MRSA colitis in an adult without apparent risk factors. Abdominal computed tomography (CT) showed thickening of the sigmoid colon, indicative of colitis, and empiric therapy with ciprofloxacin and metronidazole was started. Initial work-up for infection—including blood and stool cultures, and stool Clostridium difficile toxin assay—was negative. The patient’s clinical status improved but his diarrhea did not abate. Repetition of stool culture demonstrated luxuriant growth of MRSA sensitive to vancomycin. Oral vancomycin was administered and the patient’s symptoms promptly ceased.

A Novel Endoscopic Method to Relieve Food Impaction Using an Inflatable Balloon.

Food impaction in the esophagus is a relatively common medical emergency. Most of these food impactions are relieved spontaneously. But for complete esophageal food impactions or impactions not relieved spontaneously, traditional endoscopic methods like using a Roth net, polypectomy snare, or rat or alligator tooth forceps are used to gently manipulate the food material into the stomach. However, these methods may not work in certain circumstances. We present a case of proximal esophageal food impaction that was relieved using an inflatable balloon after the conventional methods proved unsuccessful.

Emerging role of endoscopically placed jejunostomy tubes in the management of severe hyperemesis gravidarum: a case series

Hyperemesis gravidarum (HEG) is defined as vomiting occurring in the first 20 weeks of pregnancy, severe enough to warrant inpatient management of dehydration, objective weight loss, or prolonged duration of symptoms (Fairweather criteria). It affects up to 2% of pregnant women in the United States and can lead to adverse fetal outcomes including preterm delivery and low Apgar scores at birth. It responds well to conservative management with antiemetics and intravenous fluids in O90% of cases. However, about 2% of patients have a severe form of HEG, defined as persistent vomiting leading to O5% loss of before-pregnancy weight. Severe HEG does not respond to the standard medical therapy and can have detrimental effects on fetal well-being. In these patients, providing meaningful nutrition can be challenging. We report a series of 3 pregnant patients with severe HEG who were administered enteral nutrition through PEG-jejunostomy (PEG-J) tubes during pregnancy, resulting in successful completion of pregnancy and delivery of healthy neonates.

A case of concealed appendicular polyp on screening colonoscopy

Dear Editor: Adenomas of the appendix are rarely seen on colonoscopy. We report a case of appendicular adenoma found incidentally on colonoscopy. A 64-year-old Caucasian male came to gastroenterology clinic for a screening colonoscopy. He had a past medical history of diverticulitis 6 months ago, which was treated with antibiotics. His grandmother had gastric carcinoma and his grandfather had colon carcinoma. He also had a history of 40-pack years of smoking. Physical examination was unremarkable. Laboratory evaluation including basic metabolic profile, complete blood count, stool guaiac testing were within normal limits. Colonoscopy revealed innumerable medium-sized diverticula in the sigmoid and descending colon. During the examination of cecum, appendicular orifice appeared normal on initial inspection. However, upon suctioning some air out of the cecum, a sessile polyp was seen projecting from the appendix into cecum, measuring 10×8 mm. The polyp was completely removed by snare cautery polypectomy. Histologic examination of the polyp showed tubular adenoma without any dysplasia. The patient was then referred for an appendectomy. Appendicular neoplasia is found in 1 % (no. of annual appendectomies) of all appendectomies and account for 0.4 % of gastrointestinal tumors. However, adenomatous polyps of the appendix are uncommon with an incidence up to 8 in 10,000 appendectomies [1]. Most of these adenomas were found during surgery or on post-operative examination of the resected appendix. Pre-operative diagnosis of appendix adenoma on colonoscopy is rather rare and only a few such cases have been reported in English literature. Among the reported cases in the literature, most of the appendicular adenomas were difficult to visualize on colonoscopy. Endoscopic maneuvers that may help in detecting these adenomas include suctioning the air out of cecum to visualize the adenomas [2] and prolapsing the appendix mucosa cautiously into the cecum with a biopsy forceps [3]. Due to the difficult anatomical location, complete endoscopic removal of the appendicular polyp may not be feasible in most cases and appendectomy is therefore advisable. On appendicular resection, patients with evidence of lymph node involvement or positive appendicular margins should be referred for right hemicolectomy with local lymph node dissection. For patients refusing surgery there are no guidelines for appropriate time interval before subsequent colonoscopy. However, it may be reasonable to repeat colonoscopy at 6 months interval initially to document complete removal followed by surveillance colonoscopy every 1–3 years. A few studies have reported progression of adenomatous polyps to carcinoma-in-situ or adenocarcinoma of the appendix. It is possible that the adenomas of the appendix follow the same adenoma to carcinoma sequence as the colonic adenomatous polyps. However, more data are required to validate this observation.

Mo1818 Effect of Aging on the Fecal Microbiome in Healthy Donors for Fecal Microbiota Transplant

Background: Fecal microbiota transplant (FMT) is fast emerging as a promising therapy for recurrent clostridium difficile colitis in patients not responding to antibiotic therapy. However all patients for FMT need a fecal sample from a healthy donor. However the effect of age on the fecal microbiome of the healthy donor and its clinical efficacy, has not been examined previously. Aim: To examine fecal samples of healthy human subjects of various ages, volunteering to donate their samples for FMT by genomic analysis and clinical outcom. Methods: All healthy subjects who were rigorously screened for infectious disease and selected as donors for FMT were included in the study. Fecal samples were processed and analyzed using 16S rRNA gene amplicon sequencing. Microbiota compositions were studied using standard 16S rRNA analysis tools (CloVR-16S). Differences in bacterial phylum abundance and diversity (Shannon index) of the donor fecal microbiota were analyzed using three different cutoff for age of 50 years, 60 years and 70 years. Effect of fecal microbiota from donors of different age groups on efficacy of FMT in patients with RCDI was monitored in the GI clinic. Results: Fecal microbiota of 30 healthy donors was analyzed. The mean age of the donors was 50±15.3 years and ranged between 20 years to 82 years. Of these 30 donors, 18 (60%) were males and 26 (87%) were related to the recipients. The Shannon index did demonstrate significant increase in the fecal microbiome diversity in 70+ year old donors, as demonstrated in Figure 1. Althoughmicrobiome dissimilarity between the younger donors groups was relatively larger than the older donors groups on weighted UniFrac metric analysis, the association was not statistically significant. At phylum level, while the relative abundance of Firmicutes was higher in older groups (p<0.05), Actinobacteria was higher in younger groups (p<0.05). At family and genus level, the relative abundance of bifidobactericeae members were higher in younger group of donors than older group (p<0.05). However, despite these genomic differences in the fecal microbiota with ageing, all of our patients recovered completely from the recurrent clostridium difficile infection. Conclusion: This data suggests that there is a trend towards increase in relative abundance of Firmicutes with ageing. Furthermore the younger subjects were more dissimilar by measuring phylogenetic distances than the older donors. These observations indicate that human fecal microbiome evolves with ageing process and associated factors.