Resolution of multiply recurrent and multifocal diverticulitis after fecal microbiota transplantation.

BACKGROUND: The exact pathophysiology of diverticulitis is not well understood and may be multifactorial. Recent studies highlight dysbiosis as a plausible mechanism. FMT is a safe strategy to restore commensal colon microbiota and has proven to be an effective treatment for gastrointestinal dysbiosis such as Clostridium difficile infection (CDI). There have been no studies reporting the treatment of diverticulitis with FMT. Our aim was to describe the novel application of fecal microbiota transplantation (FMT) for the treatment of recurrent diverticulitis. CASE: We report a case of a 63-year-old woman who had a 13-year history of multiply recurrent and multifocal diverticulitis previously treated with numerous short courses of intravenous and oral antibiotics for acute flares, two segmental colon resections, and suppressive antibiotic therapy for recurrent disease. Secondary to multiple courses of antibiotics , the patient developed CDI. She was treated with a single round of FMT and subsequently stopped all antibiotics at the time of FMT. RESULTS: In 20 months of follow-up, the patient has had no further recurrence of diverticulitis or CDI. CONCLUSIONS: FMT could prove to be a novel therapy for refractory diverticulitis but requires further investigation.

CO2 embolism can complicate transanal total mesorectal excision.

BACKGROUND: Carbon dioxide (CO2) embolism is a rare but potentially devastating complication of minimally invasive abdominal and retroperitoneal surgery. Characterized by a decrease in end-tidal CO2 (ETCO2) and oxygen saturation (SpO2), CO2 emboli can cause rapid intraoperative hypotension and cardiovascular collapse. Transanal total mesorectal excision (taTME) is a novel surgical approach for rectal resection, which requires high flow CO2 insufflation in a low volume operative field. In this setting, the incidence of CO2 embolism is unknown; we evaluate three cases of intraoperative CO2 embolism that occurred during the transanal portion of the TME dissection. METHODS: All taTME cases from December 2014 to March 2018 at a single institution were reviewed. Cases of CO2 embolism were identified intraoperatively and characterized using the operative reports and anesthesia records. The transanal/pelvic insufflation included a targeted pressure of 15 mm Hg, high flow and high smoke evacuation. Physiologic derangements and management of these instances were analyzed. The postoperative course was evaluated and any complications were noted. RESULTS: A total of 80 taTME were performed for benign and malignant disease. Three patients (4%) developed intraoperative evidence of CO2 embolism. Each instance occurred during the transanal portion of the dissection. Physiologic changes were marked by abrupt decrease in end-tidal ETCO2, SpO2, and blood pressure (BP). Management included immediate release of pneumopelvis, hemodynamic support with crystalloid or vasopressors, and placement of the patient in the Trendelenburg position with left side down. Within 10 min of the acute event, all patients had return of ETCO2, SpO2, and BP to pre-event levels. There were no intraoperative or postoperative sequelae including arrhythmia, myocardial infarction, stroke or death. No cases required conversion to open. CONCLUSIONS: During taTME, rare CO2 emboli may occur in the setting of venous bleeding during pneumopelvis, causing sudden, transient cardiovascular instability. Immediate recognition of rapid decrease in ETCO2, SpO2, and BP should be followed by desufflation of pneumopelvis, patient positioning in Trendelenburg and left lateral decubitus, and hemodynamic support. Increased awareness of this potential complication and maintaining a high index of suspicion will lead to preparedness of the anesthesia and surgery teams.

Celecoxib as an Adjuvant to Fluvoxamine in Moderate to Severe Obsessive-compulsive Disorder: A Double-blind, Placebo-controlled, Randomized Trial.

INTRODUCTION: A growing body of evidence implicates inflammatory cascades in the pathophysiology of obsessive-compulsive disorder (OCD), making this pathway a target for development of novel treatments. METHODS: 50 outpatients with moderate to severe OCD participated in the trial, and underwent 10 weeks of treatment with either celecoxib (200 mg twice daily) or placebo as an adjuvant to fluvoxamine. Participants were investigated using Yale-Brown Obsessive Compulsive Scale (Y-BOCS). The main outcome measure was to assess the efficacy of celecoxib in improving the OCD symptoms. RESULTS: General linear model repeated measures demonstrated significant effect for time × treatment interaction on the Y-BOCS total scores [F (1.38, 66.34)=6.91, p=0.005]. Kaplan-Meier estimation with log-rank test demonstrated significantly more rapid response in the celecoxib group than the placebo group (p<0.001). There was no significant difference in adverse event frequencies between the groups. DISCUSSION: The results of the current study suggest that celecoxib could be a tolerable and effective adjunctive treatment for more rapid and more satisfying improvements in OCD symptoms.

Atorvastatin treatment improves diabetic polyneuropathy electrophysiological changes in non-insulin dependent diabetic patients: a double blind, randomized clinical trial.

AIM: Statins are widely used amongst diabetic patients. Recently, it has been proposed that they may exert many beneficial effects on vascular function regardless of their cholesterol lowering action. There are also growing concerns about statins-induced polyneuropathy in diabetic patients. As far as we know, this is the first clinical trial that has studied the effect of atorvastatin on electrophysiological parameters in diabetic neuropathy. METHODS: This was a randomized, double-blind, placebo-controlled clinical trial that assessed nerve conduction velocity (NCV) parameters after a six-month therapy with atorvastatin, 20 mg per day. RESULTS: Although there was an 11% difference in Motor to F-wave conduction velocity ratio (M/F ratio) between the studied group and the controls, this difference was not statistically significant. Motor conduction velocity (MCV) significantly improved by 5% (P<0.05) and the F wave was not significantly deteriorated. CONCLUSION: In conclusion, treatment with statins may have a beneficial effect on diabetic neuropathy electrophysiological changes, at least in the short-term.

Efficacy of topical phenytoin on chemotherapy-induced oral mucositis; a pilot study.

BACKGROUND AND THE PURPOSE OF THE STUDY: Oral mucositis is one of the most common complications of malignancy chemotherapy. As yet, no absolute treatment has been demonstrated to be effective for chemotherapy-induced oral mucositis. This study evaluates the effectiveness of phenytoin mouthwash as a wound healing agent, on the basis of stimulating effects on fibroblast proliferation. MATERIALS AND METHODS: In this multicenter, randomized, placebo-controlled clinical trial; twelve patients received phenytoin mouthwash (0.5%) or placebo for about two weeks. Oral pain severity was scored on the daily basis using a VAS (visual analogue scale) of 10 centimeters. National Cancer Institute (NCI) scale was used to grade the intensity of mucositis. To determine the effect of treatment, a quality of life questionnaire, consisting of 35 queries, was filled out for all patients. Statistical analyses of data was performed using Mann-Whitney test. RESULTS: The average time for complete remission of mucositis in phenytoin-treated group was less than that of the placebo group. The quality of life improved dramatically in the phenytoin group with the healing process being more evident in the first week. Furthermore, reduction in the wound area was greater in the phenytoin group than controls at the end of the first week of treatment. Both groups eventually demonstrated reduction in pain intensity; however no statistically significant difference was observed between two groups. CONCLUSION: Phenytoin mouthwash accelerated wound healing and resolution of mucositis and improved life quality impressively.

Blastomyces dermatitidis of the perianal skin: report of a case.

Isolated fungal infections of the perianal skin are rare and their diagnosis is frequently overlooked. We report a case of a 78-year-old male patient who presented with a friable, violaceous, papulopustular lesion, with heaped-up edges along the anal verge. Biopsy revealed unicellular yeast consistent with blastomycosis. The patient was treated with itraconazole with resolution of this lesion. An extensive MEDLINE literature review from 1958 to the present indicates that this is an uncommon manifestation of cutaneous blastomycosis. A summary of the medical literature is presented with a review of the characteristics, diagnosis, and management of blastomycosis.

GLP-2alpha accelerates recovery of mucosal absorptive function after intestinal ischemia/reperfusion.

BACKGROUND/PURPOSE: The authors' previous laboratory results have shown that rats treated for 3 days with intravenous GLP-2alpha, a synthetic protease-resistant form of glucagonlike peptide-2, showed increased mucosal mass and absorptive function when compared with saline-treated controls after intestinal ischemia/reperfusion (I/R). This study was designed to explore the temporal relationship between injury that occurs secondary to intestinal I/R and recovery of mucosal absorptive function with and without GLP-2alpha treatment. METHODS: Each of 18 male Sprague-Dawley rats (300 to 333 g) was subjected to superior mesenteric artery occlusion for 30 minutes, during which time a jugular venous catheter was placed and connected to a subcutaneous infusion pump. Rats were divided into 4 groups based on the type and duration of infusion as follows: group 1, systemic saline at 1 microL/h for 24 hours (n = 5); group 2, systemic GLP-2alpha at 100 microg/kg/d for 24 hours (n = 5); group 3, systemic saline at 1 microL/h for 72 hours (n = 4); and group 4, systemic GLP-2alpha at 100 microg/kg/d for 72 hours (n = 4). Immediately after the infusions, (14)C-galactose and (14)C-glycine absorption was measured using an in vivo, closed-recirculation technique and expressed as micromoles per square centimeter intestine +/- SEM. Statistical analysis was performed using analysis of variance. RESULTS: Twenty-four hours after intestinal I/R injury, there was a decrease in substrate absorption but no significant difference between the saline and GLP-2alpha-treated groups (galactose absorption, 1.13 +/- 0.09 in group 1 v 1.35 +/- 0.11 in group 2, P =.15; glycine absorption, 1.18 +/- 0.13 in group 1 v 1.34 +/- 0.15 in group 2, P =.36). However, after the 72-hour infusion, absorption of galactose and glycine was significantly increased in the rats receiving GLP-2alpha as compared with the saline-infused control group (galactose absorption, 1.24 +/- 0.13 in group 3 v 1.88 +/- 0.10 in group 4, P <.01; glycine absorption, 1.64 +/- 0.07 in group 3 v 2.05 +/- 0.08 in group 4, P <.05). Compared with previously determined levels of absorption in normal, uninjured rat intestine (1.50 +/- 0.12 micromol/cm(2) for galactose and 1.85 +/- 0.17 micromol/cm(2) for glycine), after I/R a 72-hour infusion of GLP-2alpha increased galactose absorption 26% (P <.05) and glycine absorption 11% (P =.29) beyond baseline. CONCLUSIONS: When initiated at the time of intestinal I/R, a continuous infusion of GLP-2alpha accelerated recovery of mucosal absorptive function in rats. Remarkably, carbohydrate absorption at 72 hours was increased to a level significantly greater than that in normal, uninjured rat intestine. J Pediatr Surg 36:570-572.

Glucagonlike peptide-2 analogue enhances intestinal mucosal mass and absorptive function after ischemia-reperfusion injury.

BACKGROUND/PURPOSE: This study was designed to explore the efficacy of a synthetic analogue of glucagonlike peptide-2 (GLP-2a) in enhancing mucosal mass and absorptive function in a rat model of intestinal ischemia-reperfusion (I-R) injury. METHODS: Each of 20 Sprague-Dawley rats underwent placement of a jugular venous catheter connected to a subcutaneous osmotic pump designed to deliver its contents over 3 days. Rats were divided into 4 groups (n = 5 per group): (1) normal intestine/saline infusion; (2) 30-minute superior mesenteric artery occlusion/saline infusion, (3) normal intestine/ GLP-2alpha infusion, and (4) 30-minute superior mesenteric artery occlusion/GLP-2alpha infusion. Subsequently, mean mucosal 14C-galactose and 14C-glycine absorption and DNA content were determined for each group. RESULTS: In saline-treated rats, 30 minutes of mesenteric ischemia decreased mean mucosal galactose absorption by 29% (P < .05), glycine absorption by 22% (P = .12), and DNA content by 28% (P < .01) when compared with rats with uninjured intestine. In rats subjected to 30 minutes of intestinal ischemia, GLP-2alpha significantly improved galactose absorption by 46% (P < .05), glycine absorption by 84% (P < .01), and DNA content by 63% (P < .01) when compared with saline-treated control rats. In rats with mesenteric I-R injury treated with GLP-2a, galactose absorption was returned to normal. Glycine absorption and DNA content were increased significantly by 44% (P < .01) and 18% (P < .05), respectively, beyond the baseline for normal intestine. CONCLUSIONS: Thirty minutes of intestinal ischemia followed by immediate reperfusion significantly decreased mucosal mass and absorptive function, validating this rat model of I-R injury. After mesenteric I-R, GLP-2a significantly increased mucosal DNA content and absorption of 14C-galactose and 14C-glycine when compared with untreated control rats. After I-R injury, GLP-2a restored mucosal mass and absorptive function to normal or above-normal levels.

Treatment of inflammatory bowel disease in a rodent model with the intestinal growth factor glucagon-like peptide-2.

BACKGROUND/PURPOSE: Microinjection of a Fisher (F344) rat zygote with human HLA-B27 and beta2-microglobulin genes induces spontaneous chronic gastrointestinal (GI) inflammation similar to lesions seen in patients with inflammatory bowel disease (IBD). This study was designed to evaluate the potential therapeutic benefit of GLP-2, an intestinal growth factor, in this transgenic rat model of IBD. METHODS: Five F344 (control) and 10 HLA-B27 (on a F344 background) rats at 25 weeks of age were used. Rats were divided into the following 3 groups: group 1, F344 rats, no treatment (n = 5); group 2, HLA-B27, no treatment (n = 5); and group 3, HLA-B27, treated with a 14-day systemic infusion (via the jugular vein) of GLP-2 at 50 microg/kg/d (n = 5). After infusion, all rats underwent laparotomy, and the intestine from the ligament of Treitz to the rectum was harvested. Total mucosal damage (percent surface area) was measured using image analysis software (Sigmascan 2.0). Microscopic analysis was performed by a blinded reviewer and scored as follows: 0, no inflammation; 1, mild inflammation; 2, moderate inflammation; and 3, severe inflammation. Colonic mucosal total RNA was assayed for tumor necrosis factor alpha (TNF-alpha), interferon-gamma (IFN-gamma), interleukin-2 (IL-2), and glyceraldehyde-3-phosphate dehydrogenase (GAPDH), internal standard, mRNA by reverse transcriptase polymerase chain reaction. Statistical analysis was performed using analysis of variance (ANOVA) and expressed as mean +/- SEM. RESULTS: Normal F344 rats did not show evidence of gross or histological lesions in the small or large intestine. GLP-2 reduced total mucosal damage from 9.0% +/- 0.7% in group 2 to 0.9% +/- 0.5% in group 3 (P < .01). The histological lesion score was reduced from 7.0 +/- 0.6 in group 2 to 4.4 +/- 0.8 in group 3 (P < .01). Furthermore, GLP-2 reduced the mean band intensity (MBI) of TNF-alpha (0.4 +/- 0.04 in group 2 to 0 in group 3, P < .01) and IFN-gamma (0.3 +/- 0.02 in group 2 to 0 in group 3, P < .01). CONCLUSIONS: These data show for the first time that GLP-2 significantly reduces gross (90% decrease) and histological (40% decrease) lesions in this rat model of IBD. This is further supported by a significant decrease in gene expression of the inflammatory mediators TNF-alpha (100% decrease) and IFN-gamma (100% decrease). These data suggest a potential therapeutic role for GLP-2 in IBD.

Interleukin-11 enhances small intestine absorptive function and mucosal mass after intestinal adaptation.

BACKGROUND/PURPOSE: Interleukin-11 (IL-11) recently has been shown to enhance mucosal mass after massive small bowel resection (MSBR). However, enhanced mucosal mass may not correlate with increased substrate absorption. This study was designed to examine the effect of systemic administration of increasing doses of IL-11 on small intestine absorptive function and mucosal mass after MSBR. METHODS: Twenty-five Sprague-Dawley rats underwent an 80% small bowel resection and end-to-end jejunoileal anastomosis. Seven days after resection, all rats had placement of a jugular venous catheter connected to a subcutaneously placed osmotic pump. The rats were divided into 5 groups based on the content of the pump: group 1 (control, n = 5) received 0.1% bovine serum albumin (BSA) and groups 2 through 5 (n = 5 each) received IL-11 at 250, 500, 750, and 1,000 microg/kg/d, respectively. After a 14-day infusion period, [14C] galactose and [14C] glycine absorption was measured using an in vivo closed-recirculation technique. Mucosal DNA content also was determined for each group. Statistical analysis was performed by analysis of variance and expressed as mean +/-SEM. RESULTS: IL-11 administered at 250 microg/kg/d, a dose used in previous studies, did not significantly affect substrate absorption. However, compared with the control group, administration of higher doses of IL-11 produced a significant increase in substrate absorption and mucosal mass. The dose of IL-11 producing the overall optimal response based on the parameters measured (galactose absorption, 72% increase over control; glycine absorption, 112% increase over control; and DNA content, 98% increase over control) was 750 microg/kg/d. CONCLUSIONS: In addition to an increase in mucosal mass, these data show for the first time that IL-11 enhances absorptive function beyond the normal adaptive response after MSBR. Furthermore, the maximum effect of IL-11 on absorptive function was shown at 750 microg/kg/d, which is 3 times the dose used in previously reported studies. This study suggests that IL-11 may be useful clinically in patients with inadequate intestinal function.

Glucagonlike peptide-2 analogue enhances intestinal mucosal mass after ischemia and reperfusion.

BACKGROUND/PURPOSE: Glucagonlike peptide-2 (GLP-2), a product of the posttranslational processing of proglucagon, has been shown to enhance mucosal mass and function in both normal intestine and in the residual intestine after massive small bowel resection. This study was designed to determine if a synthetic, protease-resistant analogue of GLP-2 (GLP-2alpha) can enhance mucosal mass in small intestine after ischemia and reperfusion (I/R) injury. METHODS: Ten young adult male Sprague-Dawley rats underwent laparotomy and superior mesenteric artery occlusion for a period of 40 minutes. During this period of ischemia, each rat underwent placement of a jugular venous catheter that was connected to a subcutaneously placed osmotic pump designed to deliver its contents over 3 days. The rats were divided into 2 groups based on the contents of the pumps: group 1, saline at 1 microL/h (n = 6) and group 2, GLP-2alpha at 100 microg/kg/d (n = 4). Three days after insertion of the pumps the small intestine was harvested from the surviving rats for determination of mucosal DNA and protein content. Statistical analysis was performed using unpaired Student's t test. RESULTS: After I/R injury to the small intestine, a 3-day systemic infusion of GLP-2alpha significantly increased mucosal DNA content 41% (P<.05) and mucosal protein content 60% (P<.05) when compared with saline-treated controls. In addition, infusion of GLP-2alpha reduced mortality from 50% to 25%. CONCLUSIONS: These data show for the first time that GLP-2alpha enhances mucosal mass following I/R injury to the small intestine. GLP-2alpha may be of benefit to patients with intestinal ischemia syndromes such as necrotizing enterocolitis and midgut volvulus.

Enteral glutamine does not enhance the effects of hepatocyte growth factor in short bowel syndrome.

PURPOSE: This study was designed to determine if luminally administered glutamine alone functions as a growth factor or is synergistic with hepatocyte growth factor (HGF) after massive small bowel resection (MSBR). METHODS: Twenty Sprague-Dawley rats underwent an 80% small bowel resection and jejunostomy tube placement. Seven days later the rats were divided into four groups: group 1, control, no further treatment (n = 5); group 2 received glutamine (4% of total food intake per day) via an orogastric tube (n = 5); group 3 received intraluminal HGF via a jejunostomy tube at 75 microg/kg/d (n = 5); and group 4 received glutamine and HGF at the same doses, respectively. After a 14-day HGF infusion, glutamine feeding, or both combined, [C14] glycine absorption (micromol/L/cm2 intestine) and mucosal DNA and protein content (microg/mg mucosa) were measured in the remaining small bowel. RESULTS: Glutamine alone had no effect on substrate absorption and protein or DNA content. HGF increased galactose absorption (106% increase over control, P<.01), glycine absorption (95% increase over control, P<.05), protein content (44% increase over control, P<.01), and DNA content (32% increase over control, P<.01). The combination of glutamine and HGF did not prove to be synergistic. CONCLUSIONS: These data demonstrate that in this short bowel model, glutamine alone did not enhance intestinal function. Furthermore, glutamine is not synergistic with HGF. This study suggests that glutamine alone may not be useful clinically in patients with inadequate intestinal function.

Effect of dietary obesity on naloxone disposition in sheep.

Naloxone is an opioid antagonist used frequently in studies of appetite regulation in lean and obese animals and humans. Body condition may affect plasma and tissue distribution of injected naloxone and thus confound interpretation of responses to naloxone in lean compared with obese subjects. The objective of this experiment was to determine the effect of dietary obesity per se on the pharmacokinetic behavior of iv-injected naloxone (3 mg/kg) in lean (46 kg body weight) and dietary obese (77 kg body weight) sheep that were maintained at equilibrium weight. To this end, an HPLC procedure combined with electrochemical detection was developed for measuring naloxone in sheep plasma. Naloxone disappearance from plasma followed an apparent first-order process, the kinetics of which were described best using a two-compartment open model. Components of the biexponential equations describing the plasma concentration (C)-time (t) curves for naloxone disappearance in lean (Ct = 1814e(-0.190t) + 413e(-0.017t)) and obese (Ct = 2282e(-0.282t) + 573e(-0.018t)) sheep were similar (p > 0.05). Mean (+/- SE) elimination half-lives for naloxone in lean (42.7 +/- 4.6 min) and obese (44.3 +/- 10.2 min) sheep were similar (p > 0.05). Volume of distribution of naloxone (Vd) was extensive but also similar (p > 0.05) in lean (5.6 +/- 0.9 L/kg) and obese (4.1 +/- 0.6 L/kg) sheep. Naloxone was distributed extensively throughout the body fluids and trapped or stored in significant amount in extravascular tissues because the naloxone Vd greatly exceeded 100% of body weight in both lean (557 +/- 86 mL/100 g) and obese (413 +/- 58 mL/100 g) sheep.(ABSTRACT TRUNCATED AT 250 WORDS)

Myocardial viability in patients with chronic coronary artery disease. Comparison of 99mTc-sestamibi with thallium reinjection and [18F]fluorodeoxyglucose.

BACKGROUND: 99mTc-sestamibi and thallium imaging have similar accuracy when used for diagnostic purposes, but whether sestamibi provides accurate information regarding myocardial viability in patients with chronic coronary artery disease has not been established. Since there is minimal redistribution of sestamibi over time, it may overestimate nonviable myocardium in patients with left ventricular dysfunction, in whom blood flow may be reduced at rest. METHODS AND RESULTS: We studied 54 patients with chronic coronary artery disease with a mean ejection fraction of 34 +/- 14%. Patients underwent stress/redistribution/reinjection thallium tomography and, within a mean of 5 days, same-day rest/stress sestamibi imaging using the same exercise protocol and with patients achieving the same exercise duration. Of the 111 reversible thallium defects on either the redistribution or reinjection study, 40 (36%) were determined to be irreversible on the rest/stress sestamibi study, whereas only 3 of 63 irreversible thallium defects despite reinjection (5%) were classified to be reversible by sestamibi imaging. The concordance regarding reversibility of myocardial defects between thallium stress/redistribution/reinjection and same day rest/stress sestamibi studies was 75%. A subgroup of 25 patients also underwent positron emission tomography (PET) studies with 15O-labeled water and [18F]fluorodeoxyglucose (FDG) at rest after an oral glucose load. As in the overall group of 54 patients, there was concordance between thallium and sestamibi imaging regarding defect reversibility in 51 of 73 regions (70%). In the remaining 22 discordant regions (30%), 18 (82%) appeared irreversible by sestamibi imaging but were reversible by thallium imaging. Myocardial viability was confirmed in 17 of 18 regions, as evidenced by normal FDG uptake (10 regions) or FDG/blood flow mismatch (7 regions) on PET. These regions were present in 16 of the 25 patients studied (64%). We then explored methods to improve the sestamibi results. First, when the 18 discordant regions with irreversible sestamibi defects were further analyzed according to the severity of defects, 14 (78%) demonstrated only mild-to-moderate reduction in sestamibi activity (51% to 85% of normal activity), suggestive of predominantly viable myocardium, and the overall concordance between thallium and sestamibi studies increased to 93%. Second, when an additional 4-hour redistribution image was acquired in 18 patients after the injection of sestamibi at rest, 6 of 16 discordant irreversible regions (38%) on the rest/stress sestamibi study became reversible, thereby increasing the concordance between thallium and sestamibi studies to 82%. CONCLUSIONS: These data indicate that same-day rest/stress sestamibi imaging will incorrectly identify 36% of myocardial regions as being irreversibly impaired and nonviable compared with both thallium redistribution/reinjection and PET. However, the identification of reversible and viable myocardium can be greatly enhanced with sestamibi if an additional redistribution image is acquired after the rest sestamibi injection or if the severity of reduction in sestamibi activity within irreversible defects is considered.