Thromboembolic Events in Hospitalized Patients with Inflammatory Bowel Disease.

BACKGROUND: Inflammatory bowel disease (IBD) has been associated with an increased risk of thromboembolic vascular complications. Although studies from the National Inpatient Sample (NIS) examined this association to some extent, sub-stratification for Crohn's disease (CD) and ulcerative colitis (UC) in larger studies is lacking. The aims of this study were to utilize the NIS to determine the prevalence of thromboembolic events in inpatients with IBD compared to in patients without IBD and to explore the inpatient outcomes like morbidity, mortality, and resource utilization in patients with IBD and thromboembolic events as stratified by disease subtype. METHODS: This was a retrospective observational study using the NIS 2016. All patients with ICD10-CM codes for IBD were included. Patients with thromboembolic events were identified using diagnostic ICD codes and stratified into 4 categories: (1) Deep vein thrombosis (DVT), (2) Pulmonary embolism (PE), (3) Portal vein thrombosis (PVT), and (4) Mesenteric ischemia, which were then sub-stratified for CD and UC. The primary outcome was the inpatient prevalence and odds of thromboembolic events in patients with IBD compared to without IBD. Secondary outcomes were inpatient morbidity, mortality, resource utilization, colectomy rates, hospital length of stay (LOS), and total hospital costs and charges compared to patients with IBD and thromboembolic events. RESULTS: A total of 331,950 patients with IBD were identified, of who 12,719 (3.8%) had an associated thromboembolic event. For the primary outcome, after adjusting for confounders, inpatients with IBD had higher adjusted odds of DVT (aOR 1.59, p < 0.001), PE (aOR 1.20, p < 0.001), PVT (aOR 3.18, p < 0.001) and mesenteric ischemia (aOR 2.49, p < 0.001) compared to inpatients without IBD, an observation which was confirmed for both patients with CD and UC. Inpatients with IBD and associated DVT, PE and mesenteric ischemia had higher morbidity, mortality, odds of colectomy, cost, and charges. CONCLUSIONS: Inpatients with IBD have higher odds of associated thromboembolic disorders compared to patients without IBD. Furthermore, inpatients with IBD and thromboembolic events have significantly higher mortality, morbidity, colectomy rates and resource utilization. For these reasons, increased awareness and specialized strategies for the prevention and management of thromboembolic events should be considered in inpatients with IBD.

Effects of NGM282, an FGF19 variant, on colonic transit and bowel function in functional constipation: a randomized phase 2 trial.

OBJECTIVE: NGM282 is an analog of fibroblast growth factor 19 (FGF19), a potent inhibitor of bile acid (BA) synthesis in animals and humans. In phase 2 trials in type 2 diabetes and primary biliary cholangitis, NGM282 was associated with dose-related abdominal cramping and diarrhea. We aimed to examine effects of NGM282 on colonic transit, stool frequency and consistency, hepatic BA synthesis (fasting serum C4), fecal fat, and BA in functional constipation (FC). METHODS: Two-dose NGM282 (1 and 6 mg, subcutaneously daily), parallel-group, randomized, placebo-controlled, 14-day study in patients with FC (Rome III criteria) and baseline colonic transit 24 h geometric center (GC) <3.0. We explored treatment interaction with SNPs in genes KLB, FGFR4, and TGR5 (GPBAR1). STATISTICAL ANALYSIS: overall ANCOVA at α = 0.025 (baseline as covariate where available), with three pairwise comparisons among the three groups (α = 0.008). RESULTS: Overall, NGM282 altered bowel function (number of bowel movements, looser stool form, and increased ease of passage) and significantly accelerated gastric and colonic transit. Dose-related effects were seen with GC 24 h, but not with gastric emptying (GE) and GC 48 h. There were no differences in fecal fat or weight, but there was reduced fecal total BA excretion with NGM282. The most common adverse events were increased appetite (n = 0 with placebo, 2 with 1 mg, 9 with 6 mg), injection site reaction (n = 2 placebo, 4 with 1 mg, 8 with 6 mg), and diarrhea (n = 1 with 1 mg and 4 with 6 mg NGM282). There was treatment interaction with KLB SNP, with greater increase in colonic transit in participants with the minor A allele (p = 0.056). CONCLUSION: NGM282 significantly impacts GE and colonic transit, consistent with the observed clinical symptoms. The specific mechanism of prokinetic activity requires further research.

Comparison of efficacy of pharmacological treatments for chronic idiopathic constipation: a systematic review and network meta-analysis.

OBJECTIVE: To compare efficacy of pharmacotherapies for chronic idiopathic constipation (CIC) based on comparisons to placebo using Bayesian network meta-analysis. DATA SOURCES: We conducted searches (inception to May 2015) of MEDLINE, EMBASE, Scopus and Cochrane Central, as well as original data from authors or drug companies for the medications used for CIC. STUDY SELECTION: Phase IIB and phase III randomised, placebo-controlled trials (RCT) of ≥4 weeks' treatment for CIC in adults with Rome II or III criteria for functional constipation; trials included at least one of four end points. DATA EXTRACTION AND SYNTHESIS: Two investigators independently evaluated all full-text articles that met inclusion criteria and extracted data for primary and secondary end points, risk of bias and quality of evidence. OUTCOMES: Primary end points were ≥3 complete spontaneous bowel movements (CSBM)/week and increase over baseline by ≥1 CSBM/week. Secondary end points were change from baseline (Δb) in the number of SBM/week and Δb CSBM/week. RESULTS: Twenty-one RCTs (9189 patients) met inclusion and end point criteria: 9 prucalopride, 3 lubiprostone, 3 linaclotide, 2 tegaserod, 1 each velusetrag, elobixibat, bisacodyl and sodium picosulphate (NaP). All prespecified end points were unavailable in four polyethylene glycol studies. Bisacodyl, NaP, prucalopride and velusetrag were superior to placebo for the ≥3 CSBM/week end point. No drug was superior at improving the primary end points on network meta-analysis. Bisacodyl appeared superior to the other drugs for the secondary end point, Δb in number of SBM/week. CONCLUSIONS: Current drugs for CIC show similar efficacy. Bisacodyl may be superior to prescription medications for Δb in the number of SBM/week in CIC.

Rectal Gas Volume Measured by Computerized Tomography Identifies Evacuation Disorders in Patients With Constipation.

BACKGROUND & AIMS: Approximately one third of patients who present to gastroenterology care with constipation have rectal evacuation disorders. We aimed to compare rectal gas volume, measured by computerized tomography (CT), in constipated patients with and without rectal evacuation disorders. METHODS: In a retrospective study, we collected data from 1553 patients with constipation, evaluated over 20 years. We analyzed data from 141 patients evaluated by anorectal manometry, balloon expulsion tests, and colon transit tests, collecting records of abdominal and pelvic CT examinations. Patients were classified into 3 subgroups: those with rectal evacuation disorders, slow-transit constipation, or normal-transit constipation. Two observers used standard CT software to identify variable regions of interest on each cross-sectional CT image that contained rectum and measured areas of gas in each slice; they then summated entire volumes of rectal gas. For the 3 groups, we compared rectal gas volume, maximal rectal gas transaxial area (measured by CT), and area of rectal gas (vertical) on the 2-dimensional abdominal film (scout) using the Kruskal-Wallis test. RESULTS: The intraclass correlation coefficient between 2 observers' measurements of rectal gas volume was 0.99 (P < .001). There were overall group differences in rectal gas volume and the maximal rectal gas transaxial area (both P < .001). The median rectal gas volume was higher in patients with rectal evacuation disorders (13.84 cm3) than in patients with slow-transit (2.51 cm3) or normal-transit constipation (1.33 cm3, both P < .05). Similarly, the area of rectal gas, which correlated with the maximal rectal gas transaxial area (Spearman correlation coefficient, 0.7; P < .001), showed overall 3-group differences (P = .033), with greater areas of rectal gas on the abdominal scout film in patients with rectal evacuation disorders than in those with normal-transit constipation. CONCLUSIONS: In an analysis of patients with constipation, we found rectal gas volume, determined by abdominal CT imaging, to be greater in patients with than without rectal evacuation disorders.

Biomarkers for bile acid diarrhoea in functional bowel disorder with diarrhoea: a systematic review and meta-analysis.

There is no universally available laboratory test to diagnose bile acid diarrhoea (BAD). OBJECTIVE: To conduct a systematic review and meta-analysis to identify a biomarker for idiopathic BAD in patients with functional bowel disorder (FBD) with diarrhoea. DESIGN: We searched multiple databases through 15 May 2015. Data were only available to estimate the diagnostic yield of each test (the prevalence of a positive test). Estimates were pooled across studies using the random effects model. RESULTS: We included 36 studies, enrolling 5028 patients (24 using 75selenium homotaurocholic acid test (75SeHCAT) retention of <10%, 6 using fasting serum C4, 3 using fasting serum fibroblast growth factor 19 (FGF19) and 2 based on total faecal bile acid (BA) excretion over 48 h). The diagnostic yields (and 95% CI) of abnormal tests were: 0.308 (0.247 to 0.377) for 75SeHCAT retention (<10%), 0.171 (0.134 to 0.217) for serum C4, 0.248 (0.147 to 0.385) for serum FGF19 and 0.255 (0.071 to 0.606) for total faecal BA excretion over 48 h. The majority of the analyses were associated with substantial heterogeneity. Performance characteristics relative to a gold standard test could not be estimated. CONCLUSIONS: Overall, the test with the highest diagnostic yield conducted in the largest number of studies was 75SeHCAT retention, which is not widely available in many countries outside Europe and Canada. Using different diagnostic tests, 25% (average) of patients with lower FBD with diarrhoea has evidence of idiopathic BAD. These tests serve to identify idiopathic BAD among patients with FBD with diarrhoea. Further studies are required to appraise the performance characteristics of tests for idiopathic BAD.

Short-Term Effects of Relamorelin on Descending Colon Motility in Chronic Constipation: A Randomized, Controlled Trial.

BACKGROUND: The pentapeptide ghrelin agonist, relamorelin, accelerates colonic transit in patients with chronic constipation (CC). In a murine model, relamorelin decreased excitability of colonic circular smooth muscle cells and colonic intraluminal pressure. AIM: To determine short-term effects of relamorelin on colonic motility measured by barostat and multilumen manometry in CC. METHODS: In a placebo-controlled, single-dose, double-blind, randomized study in patients with CC, we investigated the motor effects of relamorelin, 100 µg, SQ (12 patients) compared to placebo SQ (six patients). A motility-barostat balloon assembly was used to measure colonic compliance; tone and phasic pressure activity were measured before and after a 1000-kcal milkshake meal (administered ~60 min post-medication). Overall "background" phasic pressure activity was assessed by: average amplitude and motility index (MI = ln[sum amplitudes × #contractions + 1]) over defined periods. High-amplitude propagating contractions (HAPCs) were characterized by amplitude >75 mmHg and propagating contractions >50 mmHg; both were propagated over at least 10 cm. Postprandial HAPCs were the primary end point. The study sample had 80% power to detect an increase of 3.3 HAPCs in the hour post-meal. RESULTS: Relamorelin, 100 µg, significantly induced more pre-meal propagated contractions [PCs of either >50 or >75 mmHg] compared to placebo (p < 0.05). Relamorelin also induced more post-meal PCs >50 or >75 mmHg than placebo. Relamorelin did not significantly alter colonic compliance, fasting or postprandial phasic pressure activity (20 min pre-meal fasting MI) or tone, and 60 min postprandial phasic pressure amplitude or MI, or tone. CONCLUSIONS: Relamorelin stimulates propagated colonic contractions without alteration of background irregular contractions in CC. ClinicalTrial.Gov registration number: NCT 01781104.

Use and Misuse of Parenteral Nutrition in Patients with Inflammatory Bowel Disease.

Malnutrition is a very common and often underrecognized condition among patients with inflammatory bowel diseases (IBD). This is most commonly due to increased nutritional requirements and gastrointestinal losses, along with reduced oral intake. Screening for malnutrition is an essential component of managing both inpatients and outpatients with IBD. Although enteral nutrition is the preferred route of supplementation, parenteral nutrition (PN) remains an important strategy and should be considered in certain situations, such as cases with short-bowel syndrome, high-output intestinal fistula, prolonged ileus, or small-bowel obstruction. Appropriate use of PN is critical in order to prevent associated complications. This review addresses the common indications for use of PN, the composition of PN, and the possible complications encountered with PN use, as well as scenarios of inappropriate PN use among patients with IBD. A clinical management algorithm for utilizing PN among patients with IBD is proposed in this review.

Malnutrition is common and underrecognized among patients with inflammatory bowel diseases (IBD). Screening for malnutrition is an essential component of IBD management. Although enteral nutrition is the preferred route of supplementation, parenteral nutrition (PN) should be considered in certain situations. Appropriate use of PN is critical to prevent associated complications.

Systematic review and network meta-analysis: efficacy of licensed drugs for abdominal bloating in irritable bowel syndrome with constipation.

BACKGROUND: Although bloating is a highly prevalent and troublesome symptom in irritable bowel syndrome with constipation (IBS-C), treatment is empirical with no specific guidelines for its management. AIM: To conduct a pairwise and network meta-analysis, using a frequentist approach, of Food and Drug Administration-licensed drugs for IBS-C comparing their efficacy for abdominal bloating as a specific endpoint. METHODS: We searched the medical literature through December 2020 to identify randomised controlled trials (RCTs) in IBS-C, with abdominal bloating reported as a dichotomous assessment. Efficacy of each drug was reported as a pooled relative risk (RR) with 95% confidence intervals (CIs) to summarise effect of each comparison tested. Treatments were ranked according to their P-score. RESULTS: We identified 13 eligible RCTs, containing 10 091 patients. Linaclotide 290 µg o.d., lubiprostone 8 µg b.d., tenapanor 50 mg b.d. and tegaserod 6 mg b.d. were all superior to placebo for abdominal bloating in patients with IBS-C, in both pairwise and the network meta-analyses. Linaclotide demonstrated the greatest improvement in abdominal bloating in both pairwise and network meta-analysis (RR of failure to achieve an improvement in abdominal bloating = 0.78; 95% CI 0.74-0.83, number needed to treat = 7, P-score 0.97). Indirect comparison revealed no significant differences between individual drugs. CONCLUSIONS: We found all licensed drugs for IBS-C to be superior to placebo for abdominal bloating. Linaclotide appeared to be the most efficacious at relieving abdominal bloating. Further research is needed to assess long-term efficacy of these agents and to better understand the precise mechanism of improving bloating.

Treatment Approach of Refractory Helicobacter pylori Infection: A Comprehensive Review.

H. pylori is the most common infection in the world and is associated with gastrointestinal and extra-gastrointestinal manifestations, including peptic ulcer disease, gastrointestinal bleeding, and lymphoproliferative disorders. Despite being discovered less than half a century ago, antibiotic resistance, exacerbated by medication non-adherence and inefficacy of proton pump inhibitors, has grown substantially, explaining the rising incidence of refractory H. pylori infection. In this review, we discuss risk factors, treatment options, surveillance and follow-up, as well as emerging therapies for refractory H. pylori.

Temporal trends of incidence and mortality in Asian-Americans with pancreatic adenocarcinoma: an epidemiological study.

BACKGROUND: Pancreatic cancer is the fourth most common cause of cancer-related deaths in the United States, with an estimated 45,750 deaths in 2019. Mortality outcomes seem to differ based on the ethnicity of the patients, with most studies focusing on the mortality and survival of Caucasians and African Americans. Little attention has been given, however, to Asian-American patients diagnosed with pancreatic adenocarcinoma (PAC). In this study, we aimed to investigate mortality rates in Asian-American patients with PAC. METHODS: The SEER 13 registries (Surveillance, Epidemiology, and End-Results) of the National Cancer Institute were used to study PAC cases during 1992-2015. The incidence and incidence-based mortality rates per 100,000 person-years, and the annual percentage changes were calculated using SEER*stat software and Joinpoint regression software. RESULTS: A total of 5814 PAC cases in Asian-American patients were identified. Most patients were older than 60 years (77.6%) and had metastatic disease (55.8%). The overall incidence of PAC among Asian-Americans was 5.740 per 100,000 person-years (95% confidence interval [CI] 5.592-5.891]. Incidence rates were highest among males and patients older than 60 years. PAC incidence rates among Asian-Americans increased by 1.503% (95%CI 1.051-1.956; P<0.001) per year over the study period. PAC incidence rates increased over the study period for all sex, age, and stage subgroups. PAC incidence-based mortality among Asian-Americans increased by 4.535% (95%CI 3.538-5.541; P<0.001) per year over the study period. CONCLUSION: The incidence of PAC in Asian-Americans, as well as incidence-based mortality rates, are on the rise, irrespective of age, sex or stage subgroup.

Opioid-induced constipation: advances and clinical guidance.

Currently opioids are the most frequently used medications for chronic noncancer pain. Opioid-induced constipation is the most common adverse effect associated with prolonged use of opioids, having a major impact on quality of life. There is an increasing need to treat opioid-induced constipation. With the recent approval of medications for the treatment of opioid-induced constipation, there are several therapeutic approaches. This review addresses the clinical presentation and diagnosis of opioid-induced constipation, barriers to its diagnosis, effects of opioids in the gastrointestinal tract, differential tolerance to opiates in different gastrointestinal organs, medications approved and in development for the treatment of opioid-induced constipation, and a proposed clinical management algorithm for treating opioid-induced constipation in patients with noncancer pain.

Characteristics of chronic megacolon among patients diagnosed with multiple endocrine neoplasia type 2B.

BACKGROUND: Gastrointestinal symptoms are frequent in multiple endocrine neoplasia (MEN) 2B and may be related to megacolon. OBJECTIVE: The objective of this article is to review the clinical features of patients with MEN 2B, particularly megacolon. METHODS: We used natural language processing of electronic medical records of Mayo Clinic patients over 20 years: Eight patients with definite MEN 2B were identified; of these, four had megacolon. From these patients' records, three others with paper medical records were identified through familial association. We used a standard data sheet to identify features of the disease with particular emphasis on megacolon. RESULTS: Of the 11 patients identified with MEN 2B, seven (63%) had megacolon, typically presenting with constipation in infancy or megacolon in childhood. In addition, three patients had esophageal manifestations (two achalasia and one Zenker's diverticulum). Megacolon often required surgical intervention for intractable constipation, abdominal distension and discomfort. Histopathological features of resected colon revealed enteric and extrinsic nerve hyperplasia and ganglioneuromas of the submucosal and myenteric plexuses. CONCLUSIONS: Among patients with MEN 2B, 63% had megacolon. Significant esophageal motor disorders in MEN 2B may affect ∼25% of patients. Any presentation with megacolon should trigger a search for MEN 2B in order to identify the potentially fatal endocrine tumors.

Chronic opioid induced constipation in patients with nonmalignant pain: challenges and opportunities.

With the recent introduction and approval of medications directed at the treatment of opioid induced constipation (OIC) in patients with nonmalignant pain, there is increased interest and understanding of the unmet need and opportunities to enhance patient management. The high incidence of OIC is associated with rapid increase of narcotic analgesic prescriptions for nonmalignant chronic pain. This review addresses briefly the mechanisms of action of opioids that lead to OIC, the differential tolerance of gastrointestinal organs to the effects of opioids, the size and scope of the problem, the definition and outcome measures for OIC, current differential diagnosis and management algorithms, and the pharmacology and efficacy of treatments for OIC in patients with nonmalignant pain.