Camilleri, Michael

AbstractBackgroundColonic pseudo‐obstruction (CPO) is characterized by colonic distention in the absence of mechanical obstruction or toxic megacolon. Concomitant secretory diarrhea (SD) with hypokalemia (SD‐CPO) due to gastrointestinal (GI) loss requires further characterization.AimTo perform a systematic review of SD‐CPO, report a case study, and compare SD‐CPO with classical CPO (C‐CPO).MethodsWe performed a search of MEDLINE, EMBASE, Cochrane, and Scopus for reports based on a priori criteria for CPO, SD and GI loss of potassium. An additional case at Mayo Clinic was included.ResultsNine publications met inclusion criteria, with a total of 14 cases. Six studies had high, three moderate, and our case high methodological quality. Median age was 74 years (66‐97), with 2:1 male/female ratio. Kidney disease was present in 6/14 patients. Diarrhea was described as profuse, watery, or viscous in 10 patients. Median serum, stool, and urine potassium concentrations (mmol/L) were 2.4 (range: 1.9‐3.1), 137 (100‐180), and 17 (8‐40), respectively. Maximal diameter of colon and cecum (median) were 10.2 cm and 10.5 cm, respectively. Conservative therapy alone was effective in five out of 14 patients. Median potassium supplementation was 124 mEq/d (40‐300). Colonic decompression was effective in three out of six patients; one had a total colectomy; three out of 14 had died. The main differences between SD‐CPO and C‐CPO were lower responses to treatments: conservative measures (35.7% vs 73.6%, P=.01), neostigmine (17% vs 89.2%, P<.001), and colonic decompression (50% vs 82.4%, P=.02).ConclusionSD‐CPO is a rare phenotype associated with increased fecal potassium and is more difficult to treat than C‐CPO.

AbstractBackgroundFollowing ablation therapy for cardiac arrhythmias, patients may develop upper gastrointestinal (UGI) symptoms. The vagus nerve is close to the atria and may be affected by ablating energy.AimTo identify structural or functional complications in UGI tract following ablation for atrial fibrillation (AF) and clinical outcomes and association with vagal dysfunction.MethodsUsing natural language processing of electronic medical records and an AF ablation database of 5380 patients treated during 17 years, we identified 40 patients with UGI complications. We evaluated vagal dysfunction by electrocardiogram (ECG) showing lack of sinus arrhythmia (variation in R‐R interval by ≥120 milliseconds, in presence of normal sinus P waves and constant P‐R interval).Key ResultsAmong 40 patients: (A) eight had structural GI complications confirmed by diagnostic tests: seven with esophageal ulcer/erosions and no signs of UGI bleeding and one developed esophagopericardial fistula (and survived with treatment); (B) 15 had functional UGI complications confirmed by objective motility tests. Nine had newly developed symptoms and six had aggravated symptoms; and (C) the remaining 17 had GI symptoms without relevant diagnostic results. Most UGI issues resolved spontaneously or with conservative treatment. However, 2 died several weeks after ablation procedure; cause of death was suspected atrioesophageal fistula or esophageal rupture. Vagal dysfunction persisted for 3 months in 13 and was transient in 8.Conclusions/InferencesAlthough most GI issues resolved spontaneously, there should be a high index of clinical suspicion in patients with persistent symptoms. Vagal dysfunction may serve as a marker of more extensive tissue damage.

AbstractSerum‐derived bovine immunoglobulin/protein isolate (SBI), an oral nutritional therapy, is efficacious in diverse diarrheal diseases. In an open‐label study in 15 patients with irritable bowel syndrome‐diarrhea (IBS‐D), we evaluated effects of SBI (5.0 g, twice a day) for 8 weeks on safety, on bowel function and abdominal pain, tryptophan metabolism (K:T ratio), intestinal permeability (13C‐mannitol and lactulose excretion), bile acid synthesis (fasting serum FGF‐19 and C4), duodenal and stool microbiome, and the expression of 90 genes related to inflammation, immune function, and tight junctions in duodenal mucosa. Statistical analysis (paired tests, baseline vs. treatment) was based on intention to treat (ITT) principles. One of 15 Caucasian patients (13F, 2M, age 40.3 ± 2.3y, BMI 34.3 ± 3.0 kg/m2) withdrew without completing studies. There were improvements in stools/day (decrease, P < 0.001), ease of passage (P = 0.035), and evacuation (P = 0.004) with SBI therapy. Worst pain severity was numerically reduced in last 2 weeks' treatment (P = 0.078). Duodenal mucosal mRNA expression; serum C4, FGF‐19, and KT ratio; small bowel or colon permeability; and stool microbiome were not significantly different after SBI therapy, compared to baseline. In duodenal brushings, there was considerable microbiota structure difference (β diversity analysis P = 0.072, UniFrac) and, on taxonomic analysis, increased abundance of Proteobacteria Burkholderiales, Firmicutes Catonella, and unclassified genus organisms with SBI therapy. Thus, SBI therapy for 8 weeks in IBS‐D patients is associated with improved bowel function; the mechanism of benefit is unclear, though there were microbiota structure differences in duodenal brushings. Further studies in patients with low‐grade inflammation and intestinal barrier dysfunction at baseline are indicated.

Abstract Background Diagnosis of rectal evacuation disorders ( RED ) is currently based on anorectal manometry ( ARM ) and evacuation tests in specialized laboratories; we recently showed higher rectal gas volume ( RGV ) and maximum rectal gas transaxial area ( MRGTA ) measured on abdominal and pelvic computed tomography ( CT ) in patients with documented RED .The aim of this study was to obtain cut‐off values of RGV , MRGTA , and rectal area on scout film ( RASF ) to differentiate constipated patients with RED from those without RED , based on ARM , balloon expulsion test ( BET ), and colon transit test. Methods We identified 118 constipated patients (65 with RED ) with prior record of CT . Using standard CT software, we used a variable region of interest ( ROI ) program to measure RGV , MRTGA , and RASF , as previously described. We constructed receiver operating characteristics curves based on different values, and we estimated AUC , specificity, and positive predictive value ( PPV ) to detect RED in patients with constipation. Key Results Receiver operating characteristics of the models to predict RED showed AUC 0.751 for RGV and 0.737 for MRGTA (both P <.001), and 0.623 for RASF ( P =.029). At specificity of 90%, RGV of 30 mL had a PPV 77.3%, MRGTA of 10 cm 2 had a PPV 75.0%, and RFAS of 9 cm 2 had a PPV of 68.8% for identifying constipated patients with RED . Conclusions & Inferences Rectal gas measurements on abdominal imaging may indicate RED in patients with constipation. At ~90% specificity for RED , RGV of 20 or 30 mL or MRGTA of 10 cm 2 on CT has PPV ~75%, and RASF of >9 cm 2 has PPV of ~69%.

AbstractBackgroundIn an open‐label study of 26 patients with IBS‐C and chronic constipation, treatment with a vibrating (VIBRANT) capsule twice a week for 7.5 weeks resulted in 88.5% responders. Effects on colonic transit are unclear. We aimed to compare effects of VIBRANT and sham capsule treatment on colonic transit in patients with functional constipation.MethodsPatients with functional constipation (Rome III criteria) were randomized to VIBRANT or sham capsule treatment for 8 weeks and underwent scintigraphic colonic transit measurements during week 8. We estimated the overall rate of colonic transit from the slope of progression of colonic geometric center over 48 hours. The capsule was activated 8 hours after ingestion, and the vibration sequence included 240 cycles.Key ResultsThere were no significant group differences in overall colonic transit [GC48, 2.76 (IQR 2.42‐4.03) for sham group and 3.46 (2.55‐4.61) for active treatment group (P=.13)]. Additionally, the progression of the isotope through the colon was numerically faster, though not significantly different (slope, P=.14) in the VIBRANT capsule group compared to the sham group. Three participants in the VIBRANT capsule group had accelerated colonic transit at 32 hours and faster colonic transit slope compared to the 95th percentile of the sham group.Conclusions and InferencesAlthough there were no group differences between VIBRANT and sham capsule treatment on colonic transit, at least one (and possibly three) of 12 patients receiving the VIBRANT capsule had faster colonic transit. The vibration parameters to accelerate colonic transit in patients with functional constipation require further optimization.

AbstractBackgroundAcute generalized exanthematous pustulosis (AGEP) is a rare skin condition typically caused by medications. The objective of this study was to examine the clinical features, causes, and outcomes of AGEP at a sole tertiary care center.MethodsA retrospective review of patients with AGEP (European Study of Severe Cutaneous Adverse Reactions score of ≥ 5) seen at Mayo Clinic (Rochester, MN, USA) between January 1, 1996, and December 31, 2013, was conducted.ResultsOf 28 patients (mean age at onset: 56 years), 17 (61%) were women. The development of AGEP was attributed to medications in 25 patients (89%), with clindamycin the most common culprit (six patients). Three patients (11%) had mucous membrane involvement, and 21 (75%) showed systemic involvement. Ten patients (36%) received systemic corticosteroids for treatment of AGEP. Skin findings resolved within 15 days in 26 patients (93%) (mean time to resolution: 7.6 days). In three patients (11%), generalized skin eruptions or dermatitis developed weeks to months after the resolution of AGEP. Twenty‐four patients (86%) had a personal history of drug reactions before the development of AGEP.ConclusionsA previous history of drug reactions and clindamycin causation were more common in the present cohort than in prior reports. A small subset of patients experienced new‐onset non‐AGEP skin eruptions within a few months of the resolution of AGEP.

AbstractBackgroundThe prevalence of chronic opioid use among non‐cancer patients presenting with acute abdominal pain (AAP) is unknown. The aim was to characterize opioid use, constipation, diagnoses, and risk factors for surgical diagnoses among non‐cancer patients presenting with AAP to an emergency department (ED).MethodsWe performed a retrospective, observational cohort study of all (n=16,121) adult patients (88% from MN, IA and WI) presenting during 2014 with AAP. We used electronic medical records, and focused on 2352 adults with AAP who underwent abdominal CT scan within 24 hours of presentation. We determined odds ratios of association with constipation and features predicting conditions that may require surgery (surgical diagnosis).Key ResultsThere were 2352 eligible patients; 18.8% were opioid users. Constipation was more frequent in opioid (35.1%) compared to non‐opioid users [OR 2.88 (95% CI 2.28, 3.62)]. Prevalence of surgical diagnosis in the opioid and non‐opioid users was 35.3% and 41.7% respectively (P=.019). By univariate analysis, age and neutrophil count independently predicted increased risk, and chronic opioid use decreased risk of surgical diagnosis. Internal validation of logistic models using a randomly selected validation subset (25% of entire cohort, 587/2352) showed receiver operating characteristic (ROC) curves for the validation and full cohorts were similar.Conclusions and InferencesApproximately 19% of adults presenting with AAP were opioid users; constipation is almost three times as likely in opioid users compared to non‐opioid users presenting with AAP. Factors significantly associated with altered risk of surgical diagnoses were age, opioid use, and neutrophil count.

Amicrobial pustulosis of the folds (APF) is a rare disease characterized by aseptic pustular lesions involving cutaneous folds, typically occurring in the context of an autoimmune disorder. We present 4 patients with APF, focusing on clinical and histopathologic characteristics to improve the recognition of this entity. All 4 patients had intertriginous and extra‐intertriginous involvement. Common histopathologic features of skin biopsies in these patients were intracorneal, subcorneal, intraepidermal, perivascular, perifollicular and interstitial neutrophilic inflammation. Pustules overlying adnexal ostium and papillary dermal edema were consistently observed. The pustules were negative for microorganisms on stain testing. In these cases, associated conditions were undifferentiated connective tissue disease, systemic lupus erythematosus, antiphospholipid syndrome, Crohn disease and Hashimoto thyroiditis. The aforementioned clinical and histopathologic characteristics of patients with suspected or diagnosed connective tissue disorders should lead to suspicion for APF.