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Increased interest in cannabis as a potential treatment and/or adjuvant therapy for inflammatory bowel disease (IBD) has been driven by patients with refractory disease seeking relief as well those who desire alternatives to conventional therapies. Available data have shown a potential role of cannabis as a supportive medication, particularly in pain reduction; however, it remains unknown whether cannabis has any impact on the underlying inflammatory process of IBD. The purpose of this review article is to summarize the available literature concerning the use of cannabis for the treatment of IBD and highlight potential areas for future study.

Randomized controlled trials (RCTs) have demonstrated that therapies targeting tumor necrosis factor (TNF) and α₄β₇ integrin are effective when given as monotherapy in inducing and/or maintaining remission in patients with ulcerative colitis (UC) or Crohn's disease (CD), but data from RCTs are less clear on whether concomitant immunomodulator (IM) therapy confers additional benefit. In CD, RCT data are mixed,1,2 as are results of systematic reviews and meta-analyses, showing no benefit overall,3 minimal benefit with individual agents,4 and comparative benefit over some monotherapies but not others.5 For example, concomitant azathioprine with infliximab is more effective than either drug alone in patients with CD naive to both drugs,2 but whether combination therapy is more effective than monotherapy with infliximab in nonnaive patients, or with other approved biologic drugs in any population, remains unknown. In UC, RCTs have shown that the benefit may be limited to specific populations,6 whereas systematic reviews suggest no benefit at all.7.

Background & Aims The availability of tests for blood concentrations of anti–tumor necrosis factor (TNF) agents and antibodies against these drugs could improve dose selection for patients with inflammatory bowel disease (IBD). However, there is little consensus on when to test and how to interpret test results. We used the RAND/UCLA Appropriateness Method to determine when these tests are appropriate and how to clinically interpret their results. Methods We conducted a systematic literature search in November 2013 to identify observational or experimental studies of the measurement of anti-TNF drug and antibody concentrations in patients with IBD and interpretation of their results. We developed 35 scenarios that assessed the appropriateness of testing and 143 scenarios that addressed clinical strategies in response to test results, and presented the findings to an expert panel. The appropriateness of each scenario was rated before and after an in-person meeting with the panel. Panelists rated the appropriateness of various clinical management options including changing therapy within class, switching out of class, adjusting drug dose or interval, adding or adjusting concomitant immune modulators, and doing nothing for each of 6 permutations of high versus low drug concentrations and high, low, or undetectable antibody concentrations. Disagreement was assessed using a validated index. Results Assessment of anti-TNF drug and antibody concentrations was rated appropriate at the end of induction therapy in primary nonresponders, in secondary nonresponders, at least once during the first year of maintenance therapy, and following a drug holiday. Routine assessment in responders at the end of induction was rated uncertain. In nearly all scenarios, escalation of drug dosing was rated appropriate when drug concentration was low in the absence of antibodies, and switching within class was rated appropriate when antibodies were present. Other recommendations depended on the specific clinical scenario for which the test was obtained. Conclusions Based on the RAND/UCLA Appropriateness Method of analysis, an expert panel recommends testing for drug and antibody concentrations in many clinical scenarios. The appropriate timing and best way to respond to anti-TNF drug and antibody testing for IBD depends on the specific clinical scenario. These recommendations can help guide clinicians to best optimize anti-TNF therapy.

Background Consensus on what constitutes a quality colonoscopy report for patients with inflammatory bowel disease (IBD) is lacking. We developed a template for quality colonoscopy reporting that can be used broadly by endoscopists. Methods After a literature review of topics relevant to colonoscopy reporting, members of the Building Research in Inflammatory Bowel Disease Globally (BRIDGe) group and 2 external experts proposed candidate reporting elements. The RAND/University of California, Los Angeles appropriateness method was applied to rate the importance and feasibility of elements for inclusion in colonoscopy reports for patients with IBD. Panelists used the modified Delphi method to anonymously rate the importance and feasibility of candidate elements on a 1-to-9 scale (1-3: not important/feasible, 4-6: moderately important/feasible, 7-9: very important/feasible). Disagreement was assessed using a validated index. The panelists then met in person for discussion followed by a second round of voting. Elements rated a median of 7 or higher on importance after rerating were retained. Results One hundred two reporting elements were proposed. A total of 48 elements were retained across the four themes of "disease background," "findings and interventions," "Crohn's disease with an ileocolonic anastomosis," and "pouchoscopy." Conclusions A comprehensive list of recommended elements for quality IBD colonoscopy reporting stratified by clinical scenario has been described, using a rigorous and evidence-based approach. These elements can be incorporated into endoscopy reporting software platforms. Standardized endoscopy reporting may improve the quality of care in IBD.

Clostridium septicum (C. septicum) aortitis is a rare condition frequently associated with colon adenocarcinoma and carries a poor prognosis. We report the case of a 66-year-old man who presented with abdominal pain, blood in the stool, fever and chills. Laboratory tests were significant for leukocytosis and microcytic anemia. Abdominal imaging revealed a right colon mass and aortitis. Colonoscopy confirmed the right colon mass and also discovered a rectal mass, both adenocarcinomas. Treatment consisted of antibiotics, aortic repair, right hemi-colectomy and later trans-anal excision of the rectal mass. Blood cultures and the aortic specimen grew C. septicum. The patient improved and was doing well in follow up. Keywords Clostridium septicum, aortitis, colorectal adenocarcinoma Ann Gastroenterol 2017; 30 (4): 468-470

Background & aims Therapeutic drug monitoring (TDM) is widely available for biologic therapies in patients with inflammatory bowel disease (IBD). We reviewed current data and provided expert opinion regarding the clinical utility of TDM for biologic therapies in IBD. Methods We used a modified Delphi method to establish consensus. A comprehensive literature review was performed regarding the use of TDM of biologic therapy in IBD and presented to international IBD specialists. Subsequently, 28 statements on the application of TDM in clinical practice were rated on a scale of 1 to 10 (1 = strongly disagree and 10 = strongly agree) by each of the panellists. Statements were accepted if 80% or more of the participants agreed with a score ≥7. The remaining statements were discussed and revised based on the available evidence followed by a second round of voting. Results The panel agreed on 24 (86%) statements. For anti-tumor necrosis factor (anti-TNF) therapies, proactive TDM was found to be appropriate after induction and at least once during maintenance therapy, but this was not the case for the other biologics. Reactive TDM was appropriate for all agents both for primary non-response and secondary loss of response. The panellists also agreed on several statements regarding TDM and appropriate drug and anti-drug antibody (ADA) concentration thresholds for biologics in specific clinical scenarios. Conclusion Consensus was achieved towards the utility of TDM of biologics in IBD, particularly anti-TNF therapies. More data are needed especially on non-anti-TNF biologics to further define optimal drug concentration and ADA thresholds as these can vary depending on the therapeutic outcomes assessed.

Colon ischemia (CI) is the most common form of ischemic injury of the gastrointestinal tract. Determining the precise incidence of CI is a challenging task, because of its often brief, mild nature, and frequent spontaneous resolution, as well as its misdiagnosis as other diseases. While many underlying disease conditions may predispose patients to CI, an important and possibly overlooked etiology is that of pharmacologically induced alterations of colonic blood flow. This review details the pharmacologic agents known to be associated with CI; when possible, their mechanisms of action are described. The aim of this paper is to highlight this often unrecognized cause of CI, thereby helping physicians to be aware of the association, to recognize its occurrence promptly, and to possibly reduce morbidity and mortality.

This study examines the role of the anterior cingulate in the development of attention. Task performance relying predominantly on either automatic or controlled processes was correlated with magnetic resonance imaging based measures of the anterior cingulate in 26 normal children ages 5 to 16 years. Attentional measures were assessed with a visual discrimination paradigm. Parasagittal slices from a 3-D, T1-weighted volume data set were used to obtain area measurements of the anterior cingulate. Response latencies decreased with age for both tasks. There were significant correlations between attentional performance and right, but not left, anterior cingulate measures. Performance was faster and more accurate during trials requiring predominantly controlled processes for those children with larger right anterior cingulate measures. The results are consistent with adult neuroimaging findings of activation in the right anterior cingulate during attention tasks and with lesion studies implicating greater right hemisphere involvement in attentional processes.

Analysis of cerebral magnetic resonance images of 24 subjects with Sydenham's chorea and 48 age-, height-, weight-, gender-, and handedness-matched controls demonstrated increased sizes of the caudate, putamen, and globus pallidus in the Sydenham's chorea group. In contrast, neither total cerebral, prefrontal, or midfrontal volumes or thalamic area were increased. These results indicate the selective involvement of the basal ganglia in Sydenham's chorea.NEUROLOGY 1995;45: 2199-2203

Only a few small studies have examined the effects of recent parental divorce on young adults, including how it influences attitudes toward marriage and divorce. Results from studies using parental marital status as a predictor of young adults' attitudes have been inconsistent. Other studies have suggested that parental and family conflict would be stronger predictors of young adults' marital and family attitudes. The main hypothesis of this study was that parental and family conflict would be stronger predictors of young adults' altitudes than would parental marital status. Randomly sampled, never-married, White young adults (ages 17-23) formed two groups: those with recently divorced parents (n = 231) and those with married parents (n = 213). All responded to structured tele- phone interviews. While level of family conflict did not predict any of the five attitudes measured, level of parental disagreement pre- dicted four of the live attitudes. Parental marital status predicted two of the attitudes.

Background & Aims There is no consensus on the appropriateness of concomitant immunomodulators with anti–tumor necrosis factor (TNF) therapy for Crohn's disease. Some patients benefit from concomitant immunomodulators, but concerns related to infections and lymphoma risk have dampened enthusiasm for this approach. We applied the RAND/University of California Los Angeles Appropriateness Method toward establishing appropriateness of concomitant immunomodulators and anti-TNF therapies for Crohn's disease. Methods A literature review was conducted regarding efficacy and safety of concomitant immunomodulators in the setting of anti-TNF therapy for Crohn's disease and presented to the Building Research in Inflammatory Bowel Disease Globally group, a globally diverse panel of 13 gastroenterologists clinically experienced in inflammatory bowel disease. A total of 134 scenarios were constructed using several clinical variables. Panelists used a modified Delphi method to rate the appropriateness of concomitant immunomodulators, and met to discuss and re-rate appropriateness. Disagreement was assessed using a validated index. Results Concomitant immunomodulators were generally rated appropriate for 63 scenarios, uncertain for 60 scenarios, and inappropriate for 11 scenarios. In general, concomitant immunomodulators were appropriate for those with extensive disease, shorter duration of disease, perianal involvement, prior surgery, females, and older patients (>26 y). Concomitant immunomodulators were generally rated inappropriate for young males, and in some scenarios involving uncomplicated disease. Smoking and the particular anti-TNF medication did not influence ratings. Disagreement was observed in 6 of 134 scenarios. Conclusions The appropriateness of concomitant immunomodulators with anti-TNF therapy for Crohn's disease was determined through a modified Delphi panel approach based on expert interpretation of the available literature. Clinicians should consider multiple factors when considering concomitant immunomodulators with anti-TNF treatment.

Crohn's disease (CD) and ulcerative colitis (UC) are chronic inflammatory diseases of the gastrointestinal tract. While a cure remains elusive, both can be treated with medications that induce and maintain remission. With the recent advent of therapies that inhibit tumor necrosis factor (TNF) alpha the overlap in medical therapies for UC and CD has become greater. Although 5-ASA agents have been a mainstay in the treatment of both CD and UC, the data for their efficacy in patients with CD, particularly as maintenance therapy, are equivocal. Antibiotics may have a limited role in the treatment of colonic CD. Steroids continue to be the first choice to treat active disease not responsive to other more conservative therapy; non-systemic steroids such as oral and rectal budesonide for ileal and right-sided CD and distal UC respectively are also effective in mild-moderate disease. 6-mercaptopurine (6-MP) and its prodrug azathioprine are steroid-sparing immunomodulators effective in the maintenance of remission of both CD and UC, while methotrexate may be used in both induction and maintenance of CD. Infliximab and adalimumab are anti-TNF agents approved in the US and Europe for the treatment of Crohn's disease, and infliximab is also approved for the treatment of UC.

Case Presentation MG is a 56-year-old female with no significant past medical history who presented to TJUH in October 007 with a two year history of abdominal pain and weight loss. At presentation, she described her pain as non-radiating, 7 out of 10, gnawing, burning and located in the epigastrum and left upper quadrant. The pain initially occurred approximately 15 minutes postprandially and lasted 0 minutes. Over the two year period, the pain progressed to lasting for hours following meals. Dietary modifications and food consistency did not help the pain. The patient began avoiding oral intake, and her weight declined from 1 0 to 80 pounds. She denied nausea, vomiting, diarrhea, constipation, hematochezia, melena and change in stool frequency. Over the two years prior to admission the patient had an extensive workup with multiple gastroenterologists. Her initial workup included a colonoscopy, EGD, abdominal ultrasound and computerized tomography (CT) of the abdomen and pelvis. These were all reportedly normal and the patient was diagnosed with irritable bowel syndrome and treated symptomatically with a PPI. Due to lack of improvement, a second gastroenterologist repeated the EGD/colonoscopy and diagnosed her with peptic ulcer disease secondary to multiple gastric ulcers. She was treated with a PPI and carafate. A capsule study showed gastric and jejunal ulcers with cobblestone appearance of the small bowel which led to the diagnosis of Crohn’s disease. She was treated briefly with Pentasa. The patient sought care as an outpatient at TJUH Division of Gastroenterology. Mesenteric ischemia was initially high on the differential. An MRA of the abdomen revealed patent mesenteric vessels. Other workup included gastric emptying scan, push enteroscopy, endoscopic ultrasound (EUS), full-thickness biopsy in the operating room, fasting gastrin level, and an NSAID level. These studies were mostly inconclusive. Other studies including an octreotide scan, gastrin levels, and chromogranin A levels were either normal or inconclusive. Furthermore, it was discovered that the gastric pH was . , arguing against a gastrin producing tumor as seen in Zollinger-Ellison Syndrome.

International audience; Background & AimsThere is debate over whether patients with Crohn’s disease who start anti–tumor necrosis factor (TNF) therapy after failed immunomodulator therapy should continue to receive concomitant immunomodulators. We conducted a meta-analysis of subgroups from randomized controlled trials (RCTs) of anti-TNF agents to compare the efficacy and safety of concomitant immunomodulator therapy vs anti-TNF monotherapy.MethodsWe performed a systematic review of literature published from 1980 through 2008 and identified 11 RCTs of anti-TNF agents in patients with luminal or fistulizing Crohn’s disease. We excluded RCTs of patients who were naive to anti-TNF and immunomodulator therapy. The primary end points were clinical response at weeks 4–14 and 24–30 and remission at weeks 24–30. Secondary end points included infusion site or injection site reactions and selected adverse events. A priori subgroup analyses were performed to evaluate fistula closure and the efficacy and safety of combination therapy with different anti-TNF agents.ResultsOverall, combination therapy was no more effective than monotherapy in inducing 6-month remission (odds ratio [OR], 1.02; 95% confidence interval [CI], 0.80–1.31), inducing a response (OR, 1.08; 95% CI, 0.79–1.48), maintaining a response (OR, 1.53; 95% CI, 0.67–3.49), or inducing partial (OR, 1.25; 95% CI, 0.84–1.88) or complete fistula closure (OR, 1.10; 95% CI, 0.68–1.78). In subgroup analyses of individual anti-TNF agents, combination therapy was not more effective than monotherapy in inducing 6-month remission in those treated with infliximab (OR, 1.73; 95% CI, 0.97–3.07), adalimumab (OR, 0.88; 95% CI, 0.58–1.35), or certolizumab (OR, 0.93; 95% CI, 0.65–1.34). Overall, combination therapy was not associated with an increase in adverse events, but inclusion of infliximab was associated with fewer injection site reactions (OR, 0.46; 95% CI, 0.26–0.79.)ConclusionsOn the basis of a meta-analysis, continued use of immunomodulator therapy after starting anti-TNF therapy is no more effective than anti-TNF monotherapy in inducing or maintaining response or remission. RCTs are needed to adequately assess the efficacy of continued immunomodulator therapy after anti-TNF therapy is initiated.

The pharmacology of each biologic agent is important regarding the dose required to achieve benefits, duration of therapeutic effect, and the induction of immunogenicity. Comprehension of the individual pharmacology, pharmacodynamics, and pharmacokinetics, in addition to the impact of concomitant immunomodulation on immunogenicity allows optimization of each biologic agent in the appropriate inductive or maintenance setting of IBD.

Mesenteric ischaemia results from decreased blood flow to the bowel, causing cellular injury from lack of oxygen and nutrients. Acute mesenteric ischaemia (AMI) is an uncommon disorder with high morbidity and mortality, but outcomes are improved with prompt recognition and aggressive treatment. Five subgroups of AMI have been identified, with superior mesenteric artery embolism (SMAE) the most common. Older age and cardiovascular disease are common risk factors for AMI, excepting acute mesenteric venous thrombosis (AMVT), which affects younger patients with hypercoaguable states. AMI is characterized by sudden onset of abdominal pain; a benign abdominal exam may be observed prior to bowel infarction. Conventional angiography and more recently, computed tomography angiography, are the cornerstones of diagnosis. Correction of predisposing conditions, volume resuscitation and antibiotic treatment are standard treatments for AMI, and surgery is mandated in the setting of peritoneal signs. Intra-arterial vasodilators are used routinely in the treatment of non-occlusive mesenteric ischaemia (NOMI) and also are advocated in the treatment of occlusive AMI to decrease associated vasospasm. Thrombolytics have been used on a limited basis to treat occlusive AMI. A variety of agents have been studied in animal models to treat reperfusion injury, which sometimes can be more harmful than ischaemic injury. Chronic mesenteric ischaemia (CMI) usually is caused by severe obstructive atherosclerotic disease of two or more splanchnic vessels, presents with post-prandial pain and weight loss, and is treated by either surgical revascularization or percutaneous angioplasty and stenting.

G A A b st ra ct s for Crohn's Disease (SES-CD). In UC or IBDU, clinical and endoscopic relapse was defined by Mayo score. Results: Forty-nine patients (16 CD, 33 UC/IBDU) provided the requested stool samples and comprised the study group. Of the 49 patients 15 (31%, 4 CD [25%], 11 UC/IBDU [33%]) relapsed during the one year follow-up and 34 (69%, 12 CD [75%], 22 UC/IBDU [66%]) remained in remission. Significant increase in median FC levels was seen two (120 μg/g, 0-1867, n = 15, p = 0.0014), four (108 μg/g, 7-650, n = 8, p = 0.0056), and six (120 μg/g, 0-431, n = 6, p = 0.0029) months before the actual relapse. In contrast to those with sustained endoscopic remission, patients relapsing showed constantly elevated FC levels. A cutoff of > 140 μg/g (ROC analysis) predicted relapse with a 79% specificity and a 53% sensitivity. At the moment of clinical and endoscopic relapse 4 out of 15 patients (27%, 1 CD, 3 UC) had FC < 100 μg/g. Interestingly, no difference was found in the relapse rates in patients with FC concentration under 50 or 50-100 at baseline, (p = 0.325) nor in patients with or without acute or chronic inflammatory infiltrate in biopsy specimens at baseline (p = 0.221). No significant difference was seen in median FC levels in patients having endoscopic remission and those with mild endoscopic activity at follow-up colonoscopies. Conclusion: FC seems to rise and remain elevated before the actual clinical or endoscopic relapse, suggesting that FC can be used as a surrogate marker for predicting relapse in patients with IBD, and to identifying patients requiring a close follow-up in clinical practice.

Background: Comparative effectiveness research (CER) is an emerging field that compares the relative effectiveness of alternative strategies to prevent, diagnose, or treat patients who are typical of day-to-day practice. We developed a priority list of CER topics for inflammatory bowel disease (IBD). Methods: Following the Institute of Medicine's approach, we developed and administered a survey to gastroenterologists asking for important CER topics in IBD. Two patient focus groups were convened to solicit additional CER studies. CER topics were presented to the expert panel using the RAND/UCLA methodology. Following initial ratings, the panel met to discuss and re-rate priorities. The top 10 CER topics were identified using a point-allocation system. Results: Responses were collated into 234 CER topics across 21 categories, of which 87 were prioritized for discussion and re-rated. Disagreement regarding priorities was observed in 5 of 87 studies. We utilized a point-allocation system to prioritize the top-10 CER topics. These related to comparing the effectiveness of: biomarkers in IBD; withdrawal of anti-tumor necrosis factor (TNF) or immunomodulators for Crohn's disease in remission; mucosal healing as an endpoint of treatment; infliximab levels versus standard infliximab dosing; anti-TNF monotherapy versus combination therapy in patients failing thiopurines; safety of long-term treatment options; anti-TNF versus thiopurines for prevention of postoperative recurrence; and treatment options for steroid-refractory UC. Conclusions: We systematically developed a list of high-priority IBD topics for CER based on a survey of gastroenterologists, expert review, and patient input. This list may guide IBD research toward the most important CER studies. (Inflamm Bowel Dis 2012;)

Background: Objective markers of Crohn's Disease (CD) activity have been sought as diagnostic, phenotypic, prognostic and disease activity markers. Complications such as stricture and fistula and characteristics such as TNF-antagonist responsiveness have been suggested as discreet mechanistic CD subtypes. This study explored the ability of genome wide expression profiling in whole blood to differentiate CD sub-populations. Methods: In the previously reported Phase 2b ustekinumab CERTIFI study of patients with moderate to severely active CDwho had failed or were intolerant to TNF-antagonists, whole blood samples were collected from a subset for mRNA expression profiling using Affymetrix HG-U133+ PM arrays. Baseline expression profiles were compared between patient sub-groups characterized by defined baseline disease attributes; and compared with those from samples obtained independently from healthy subjects. Expression modulations of .+/-1.5x and false discovery rate (FDR) p-value , 0.05 were considered significant. Results: Patients (n=204) with moderate to severe CD had significant expression modulations in 1725 transcripts in the whole blood compared with healthy subjects (n=49), including genes involved in inflammatory response and connective tissue disorders. A panel of 20 transcripts (including GAB2 and IL18R1) discriminated patients with only colonic (n=49) vs. strictly ileal (n=60) disease involvement. Significantly different expression modulations of 169, 321, and 151 transcripts, respectively, were identified in patients with high baseline CRP ( ≥10 mg/dL, n=97), fecal calprotectin (≥850 mg/g, n=80) or lactoferrin (. 100 mg/g, n=89) compared with patients with low baseline CRP ( ≤3 mg/dL, n=45), fecal calprotectin (≤250 mg/g, n=58), or lactoferrin (≤100 mg/g, n=107). As expected, patients with high baseline CRP, fecal calprotectin, or lactoferrin had elevated gene expressions in inflammatory pathways such as IL-6 and acute phase response signaling. In contrast, gene expression profiles did not differentiate between patients with different durations of disease (long [≥15yrs] vs. short [≤5yrs]); prior treatment response (Primary responder vs. non-responder) and treatment history (number of TNFs failed); and the presence or absence of complications (stricture/stenosis, fistula). Conclusion: Genomewide expression profiling of peripheral blood samples provides the understanding of CD at the molecular level in circulation. This is a new, non-invasive method that can be used to identify systemic markers of local pathological alterations in CD and to discriminate clinically between different CD sub-types. Table: Number of significant expression modulations between CD sub-populations

Brain magnetic resonance images (MRI) of 104 healthy children and adolescents, age 4-18, showed significant effects of age and gender on brain morphometry. Males had larger cerebral (9%) and cerebellar (8%) volumes (P0.0001 and P = 0.008, respectively), which remained significant even after correction for height and weight. After adjusting for cerebral size, the putamen and globus pallidus remained larger in males, while relative caudate size was larger in females. Neither cerebral nor cerebellar volume changed significantly across this age range. Lateral ventricular volume increased significantly in males (trend for females), with males showing an increase in slope after age 11. In males only, caudate and putamen decrease with age (P = 0.007 and 0.05, respectively). The left lateral ventricles and putamen were significantly greater than the right (P = 0.01 and 0.001, respectively). In contrast, the cerebral hemispheres and caudate showed a highly consistent right-greater-than-left asymmetry (P0.0001 for both). All volumes demonstrated a high degree of variability. These findings highlight gender-specific maturational changes of the developing brain and the need for large gender-matched samples in pediatric neuropsychiatric studies.