On the mechanisms of ion adsorption to aqueous interfaces: air-water vs. oil-water.

The adsorption of ions to water-hydrophobe interfaces influences a wide range of phenomena, including chemical reaction rates, ion transport across biological membranes, and electrochemical and many catalytic processes; hence, developing a detailed understanding of the behavior of ions at water-hydrophobe interfaces is of central interest. Here, we characterize the adsorption of the chaotropic thiocyanate anion (SCN-) to two prototypical liquid hydrophobic surfaces, water-toluene and water-decane, by surface-sensitive nonlinear spectroscopy and compare the results against our previous studies of SCN- adsorption to the air-water interface. For these systems, we observe no spectral shift in the charge transfer to solvent spectrum of SCN-, and the Gibb's free energies of adsorption for these three different interfaces all agree within error. We employed molecular dynamics simulations to develop a molecular-level understanding of the adsorption mechanism and found that the adsorption for SCN- to both water-toluene and water-decane interfaces is driven by an increase in entropy, with very little enthalpic contribution. This is a qualitatively different mechanism than reported for SCN- adsorption to the air-water and graphene-water interfaces, wherein a favorable enthalpy change was the main driving force, against an unfavorable entropy change.

When Perfect Is the Enemy of Good: Results of a RAND Appropriateness Panel on Treat to Target in Asymptomatic Inflammatory Bowel Disease.

BACKGROUND: A treat-to-target strategy for inflammatory bowel disease (IBD) recommends iterative treatment adjustments to achieve clinical and endoscopic remission. In asymptomatic patients with ongoing endoscopic activity, the risk/benefit balance of this approach is unclear, particularly with prior exposure to advanced therapies. METHODS: Using the RAND/University of California Los Angeles Appropriateness Method, 9 IBD specialists rated appropriateness of changing therapy in 126 scenarios of asymptomatic patients with ulcerative colitis and Crohn's disease and active endoscopic disease. Disease extent and behavior, prior treatment, prior complications, and recent disease progression were considered, as were factors that might influence decision-making, including age and pregnancy. Ratings were collected through anonymous survey, discussed at an in-person meeting, and finalized in a second anonymous survey. RESULTS: Panelists rated change in therapy as appropriate (i.e., expected benefit sufficiently outweighs potential harms from continuing therapy) in 96/126 scenarios, generally in patients with progressive, complicated, and/or extensive disease, while changing therapy was rated uncertain in 27 scenarios of mild and/or stable disease. Changing therapy was rated inappropriate in ulcerative colitis patients with mild and stable disease previously exposed to ≥3 therapies or with improved endoscopic activity, and in Crohn's disease patients with only scattered aphthous ulcers. The validated threshold for disagreement was not crossed for any scenario. Patient age older than 65 years and a plan for pregnancy in the next year might influence decision-making in some settings. DISCUSSION: Appropriateness ratings can help guide clinical decision-making about changing therapy to achieve endoscopic remission in asymptomatic patients with IBD until data from ongoing randomized studies are available.

Spiers Memorial Lecture: Water at interfaces.

In this article we discuss current issues in the context of the four chosen subtopics for the meeting: dynamics and nano-rheology of interfacial water, electrified/charged aqueous interfaces, ice interfaces, and soft matter/water interfaces. We emphasize current advances in both theory and experiment, as well as important practical manifestations and areas of unresolved controversy.

Agglomeration Drives the Reversed Fractionation of Aqueous Carbonate and Bicarbonate at the Air-Water Interface.

In the course of our investigations of the adsorption of ions to the air-water interface, we previously reported the surprising result that doubly charged carbonate anions exhibit a stronger surface affinity than singly charged bicarbonate anions. In contrast to monovalent, weakly hydrated anions, which generally show enhanced concentrations in the interfacial region, multivalent (and strongly hydrated) anions are expected to show a much weaker surface propensity. In the present work, we use resonantly enhanced deep-UV second-harmonic generation spectroscopy to measure the Gibbs free energy of adsorption of both carbonate (CO32-) and bicarbonate (HCO3-) anions to the air-water interface. Contrasting the predictions of classical electrostatic theory and in support of our previous findings from X-ray photoelectron spectroscopy, we find that carbonate anions do indeed exhibit much stronger surface affinity than do the bicarbonate anions. Extensive computer simulations reveal that strong ion pairing of CO32- with the Na+ countercation in the interfacial region results in the formation of near-neutral agglomerate clusters, consistent with a theory of interfacial ion adsorption based on hydration free energy and capillary waves. Simulated X-ray photoelectron spectra predict a 1 eV shift in the carbonate spectra compared to that of bicarbonate, further confirming our experiments. These findings not only advance our fundamental understanding of ion adsorption chemistry but also impact important practical processes such as ocean acidification, sea-spray aerosol chemistry, and mammalian respiration physiology.

Appropriateness of Medical and Surgical Treatments for Chronic Pouchitis Using RAND/UCLA Appropriateness Methodology.

BACKGROUND AND AIMS: The treatment of chronic pouchitis remains a challenge due to the paucity of high-quality studies. We aimed to provide guidance for clinicians on the appropriateness of medical and surgical treatments in chronic pouchitis. METHODS: Appropriateness of medical and surgical treatments in patients with chronic pouchitis was considered in 16 scenarios incorporating presence/absence of four variables: pouchitis symptoms, response to antibiotics, significant prepouch ileitis, and Crohn's disease (CD)-like complications (i.e., stricture or fistula). Appropriateness of permanent ileostomy in patients refractory to medical treatments was considered in eight additional scenarios. Using the RAND/UCLA appropriateness method, international IBD expert panelists rated appropriateness of treatments in each scenario on a 1-9 scale. RESULTS: Chronic antibiotic therapy was rated appropriate only in asymptomatic antibiotic-dependent patients with no CD-like complications and inappropriate in all other scenarios. Ileal-release budesonide was rated appropriate in 6/16 scenarios including patients with significant prepouch ileitis but no CD-like complications. Probiotics were considered either inappropriate (14/16) or uncertain (2/16). Biologic therapy was considered appropriate in most scenarios (14/16) and uncertain in situations where significant prepouch ileitis or CD-like complications were absent (2/16). In patients who are refractory to all medications, permanent ileostomy was considered appropriate in all scenarios (7/8) except in asymptomatic patients with no CD-like complications. CONCLUSIONS: In the presence of significant prepouch ileitis or CD-like complications, chronic antibiotics and probiotics are inappropriate. Biologics are appropriate in all patients except in asymptomatic patients with no evidence of complications. Permanent ileostomy is appropriate in most medically refractory patients.

Anomalous pH-Dependent Enhancement of p-Methyl Benzoic Acid Sum-Frequency Intensities: Cooperative Surface Adsorption Effects.

Vibrational sum-frequency generation (SFG) spectroscopy is used to determine the surface pKa of p-methyl benzoic acid (pMBA) at the air-water interface by monitoring the carbonyl and carboxylate stretching modes over the pH range of 2 to 12. The SFG intensities of pMBA and its conjugate base, p-methyl benzoate (pMBA-), exhibit an anomalously large enhancement over a narrow pH range (∼0.5) centered at pH 6.3 near the SFG-determined surface pKa, 5.9 ± 0.1. The increase in the surface pKa relative to the bulk value of 4.34 is consistent with the trend previously observed for long chain carboxylic acids in which the surface pKa is higher than the bulk solution pKa. SFG polarization studies help distinguish the orientation and number density contributions to this observed anomalous surface phenomenon. The large SFG intensity increase is attributed to an increase in the pMBA and pMBA- surface concentrations in this narrow pH range due to a cooperative adsorption effect between pMBA and pMBA-. This cooperativity is manifested only on the 2D air-water interface, where the interactions between the acid and base are not as dielectrically screened as in the aqueous bulk phase. Surface effects are critical to understanding and controlling the reactivity, solubility, and behavior of organic acids at interfaces and can have an impact on biomedical applications.

Appropriate Therapeutic Drug Monitoring of Biologic Agents for Patients With Inflammatory Bowel Diseases.

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.

Appropriateness of Combination Therapy for Patients With Inflammatory Bowel Diseases: One Size Still Does Not Fit All.

Randomized controlled trials (RCTs) have demonstrated that therapies targeting tumor necrosis factor (TNF) and α4ß7 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.

Appropriateness of Testing for Anti-Tumor Necrosis Factor Agent and Antibody Concentrations, and Interpretation of Results.

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.

Effects of Concomitant Immunomodulator Therapy on Efficacy and Safety of Anti-Tumor Necrosis Factor Therapy for Crohn's Disease: A Meta-analysis of Placebo-controlled Trials.

BACKGROUND & AIMS: There 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. METHODS: We 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. RESULTS: Overall, 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.) CONCLUSIONS: On 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.

Paramedic recognition of posterior circulation stroke: a vignette and focus group study.

Introduction: The main pre-hospital screening tool used for stroke in Ireland and the United Kingdom is the FAST (face, arms, speech, time) test. However, posterior circulation stroke (PCS) patients may be FAST negative on exam, presenting with sudden dizziness, headaches, visual problems, nausea and vomiting and balance/co-ordination problems. There is a lack of research into paramedic recognition of PCS, and this study sought to evaluate recognition rates among paramedics (Ps) and advanced paramedics (APs) in Ireland. Methods: A cross-sectional sequential exploratory design was chosen. An anonymous online survey was carried out, which informed focus group discussions. The survey contained six clinical vignettes, two of which were PCS presentations. Correct diagnosis, hospital destination and type of pre-alert were recorded. Focus groups were chaired by an independent moderator via Zoom. Recordings were transcribed and thematic analysis was carried out to create codes and themes. Results: One hundred and fifty-one staff members (91 Ps, 60 APs) completed the survey (response rate 40%). Of these, 67% did not recognise PCS symptoms and 77% did not choose to transport to a stroke unit. For those correctly suspecting PCS, 42% requested resus at the stroke unit and 18% requested resus in the local emergency department (ED). Two focus groups of four practitioners (n = 8) took place. Three main themes were created: (1) comfort levels with posterior stroke, with subthemes of recognition and personal experiences; (2) education, with subthemes of clinical practice guideline (CPG) issues and training issues; and (3) hospital factors, with subthemes of pre-alerting and disconnect between hospital and emergency medical services. Participants were uncomfortable with PCS recognition and bypassing their local ED. More training was called for, with a dedicated CPG. Relationships with hospital staff affected willingness to pre-alert. Conclusions: In this sample group, recognition of PCS and onward transfer to a stroke unit was low. Focus groups showed that practitioners were uncomfortable recognising PCS and bypassing a local ED without adequate training and a dedicated CPG. Relationships with hospital staff also affected pre-alert decisions.

Innovative Care for Inflammatory Bowel Disease Patients during the COVID-19 Pandemic: Use of Bedside Intestinal Ultrasound to Optimize Management.

Background: The COVID-19 pandemic caused by SARS-CoV-2 has reduced access to endoscopy and imaging. Safe alternatives, available at the bedside, are needed for accurate, non-invasive strategies to evaluate disease activity. The aim of this study is to establish the impact of clinic-based bedside intestinal ultrasound (IUS) on decision making, reduction in reliance on endoscopy and short-term healthcare utilization. Methods: We conducted a prospective observational evaluation during the COVID-19 pandemic, of the impact of a regional comprehensive care pathway to manage IBD patients consecutively recruited with acute symptoms, or suspected new diagnosis of IBD. Clinic-based access to sigmoidoscopy and bedside intestinal ultrasound were evaluated, used to direct clinical care and avoid hospitalization or hospital-based endoscopy. Results: A total of 72 patients were seen between March 15 and June 30, 2020. Of these, 57% (41/72) were female, 64% had Crohn's disease (46/72) with 14% (10/72) presenting with symptoms requiring investigation, of which 5 new cases of IBD were identified (50%). Immediate access to ultrasound and sigmoidoscopy led to meaningful changes in management in 80.5% (58/72) of patients. Active inflammation was detected by IUS alone (72.5%, 29/40) or in combination with in-clinic sigmoidoscopy (78%, 18/23) or sigmoidoscopy alone (78% 7/9). Six patients were referred to colorectal surgery for urgent surgical intervention including two patients admitted directly. Conclusion: Implementation of IUS as part of a clinical care pathway during the COVID-19 pandemic is a useful strategy to enhance care delivery and improve clinical decisions, while sparing other important acute care resources.

Assessment of variables associated with smoking cessation in Crohn's disease.

BACKGROUND: Patients with Crohn's disease (CD) who smoke have a more complicated disease course. AIMS: Our primary objective was to assess smoking related variables that were associated with smoking cessation versus continued smoking in patients with CD. METHODS: A multi-center study identified CD patients who were seen at the University of Chicago and University of Calgary IBD clinics. Patients were categorized into three subgroups: lifetime non-smokers, current smokers, or ex-smokers. Participants completed questionnaires assessing their cigarette smoking behavior. Current smokers were prospectively followed for 6 months to assess smoking status and attempts to quit. Logistic regression analysis was performed to identify factors associated with smoking cessation. RESULTS: Three hundred patients were enrolled with 148 identifying themselves as lifetime non-smokers, 70 as current smokers, and 82 as ex-smokers. Patients who reported their first cigarette within 5 min of waking were more likely to be current smokers (OR = 21; 95% CI 3.94-107.3) as compared to patients who waited greater than 60 min. Current smokers were more likely to have one or more household members who smoked compared to ex-smokers (P < 0.05). Nearly half (49%) of the current smokers were in the precontemplation stage of change (i.e. no intention to quit smoking). At the 6-month follow-up, only 11% reported they quit smoking. CONCLUSIONS: Patients who report a short time to first cigarette in the morning may have more difficulty in smoking cessation. Current smokers were more likely to have another smoker in the household compared to ex-smokers. Current smokers had low levels of motivation to quit smoking and consequently with no intervention, very few quit 6 months after the baseline assessment.

Not so FAST: pre-hospital posterior circulation stroke.

Introduction: Posterior circulation strokes account for 20% of ischaemic strokes, but may present differently to their anterior circulation counterparts. Patients may not exhibit unilateral facial weakness, speech disturbances and unilateral limb weakness, but instead present with more vague symptoms of sudden headache, dizziness, loss of balance and visual problems. This case describes a patient displaying signs and symptoms of a posterior stroke, but who eluded the FAST (face, arm, speech, time) test. Case presentation: An ambulance was called for a 60-year-old man who had a sudden onset of generalised weakness, diaphoresis and one episode of emesis at home in rural Ireland. He had a history of hypertension, hypercholesterolaemia, angina and a coronary stent placed 4 months previously. Cardiac, respiratory, abdominal, urinary and gastrointestinal exams were unremarkable. Vital signs and 12-lead electrocardiogram were normal. He was FAST negative on exam. Due to persistent dizziness, further neurological exams were carried out, showing a left visual field neglect, new nystagmus, left-sided dysmetria on finger-to-nose and heel-to-shin tests and he was unable to walk unassisted upon standing. A posterior circulation stroke was suspected, and the nearest stroke unit was pre-alerted en route. A rapid assessment and computed tomography took place at hospital, with timely thrombolysis with tissue plasminogen activator. The patient subsequently had a full neurological recovery. Conclusion: This case describes a patient displaying signs and symptoms of a posterior circulation stroke albeit being FAST negative on exam. There is potential here to improve our recognition of posterior stroke in the pre-hospital field by including additional neurological exams to the FAST test. Use of 'BEFAST' (balance, eyes, face, arm, speech, time), the finger-to-nose test, and the '5 Ds' and 'DANISH' mnemonics may help increase recognition of these subtle presentations.

Characterizing Anion Adsorption to Aqueous Interfaces: Toluene-Water versus Air-Water.

We continue our investigation of the behavior of simple ions at aqueous interfaces, employing the combination of two surface-sensitive nonlinear spectroscopy tools, broadband deep UV electronic sum-frequency generation and UV second harmonic generation, to characterize the adsorption of thiocyanate to the interface of water with toluene─a prototypical hydrophobe. We find that both the interfacial spectrum and the Gibbs free energy of adsorption closely match results previously reported for the air-water interface. We observe no relative spectral shift in the higher-energy CTTS transition of thiocyanate, implying similar solvation environments for the two interfaces. Similarly, the Gibbs free energies of adsorption agree within error; however, we expect the respective enthalpic and entropic contributions to differ between the two interfaces, similar to our earlier findings for the air-water versus graphene-water interfaces. Further experiments and theoretical modeling are necessary to quantify the mechanistic differences.

The appropriateness of concomitant immunomodulators with anti-tumor necrosis factor agents for Crohn's disease: one size does not fit all.

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.

Complementary and alternative medications in the management of inflammatory bowel disease.

The use of complementary and alternative medications (CAM), products, and therapies not considered to be part of conventional medicine is common among patients with inflammatory bowel disease (IBD). Patients often turn to these therapies as they are considered natural and safe, with significant benefit reported beyond disease control. There is emerging evidence that some of these therapies may have anti-inflammatory activity; however, robust evidence for their efficacy in modulating disease activity is currently lacking. Patients often avoid discussing the use of CAM with their physicians, which may lead to drug interactions and/or reduced adherence with conventional therapy. It is important for physicians to be aware of the commonly used CAM and current evidence behind these therapies in order to better counsel their patients about their use in the management of IBD. This narrative review provides an overview of the evidence of the more commonly used CAM in patients with IBD.

Managing the risks of IBD therapy.

Successful management of the patient with inflammatory bowel disease (IBD) involves not only the induction and maintenance of remission, but also the optimization of the benefit-to-risk equation to achieve the greatest gain in quality of life. These risks range from intolerance to prescribed medications to potentially life-threatening sequelae (eg, sepsis) of immune suppression. A proper awareness of risk on the part of the physician and education of the patient can lead to early detection and institution of an appropriate management plan, including risk management and, optimally, primary prevention (eg, prophylactic vaccination). One should take the opportunity regularly to reassess the utility and efficacy of existing therapy, with the provision of ineffective therapies mandating urgent review. Overall, optimal management of the patient with IBD requires open dialogue between clinician and patient so that both are cognizant of the goals, benefits, and potential risks of therapy.

Anti-aging therapy with human growth hormone associated with metastatic colon cancer in a patient with Crohn's colitis.

BACKGROUND & AIMS: The nonapproved use of human growth hormone (HGH) for anti-aging has been increasing. Theoretical concerns for neoplastic potentiation by HGH have been raised, but not proven clinically. METHODS: We report the case of a 68-year-old man with colonic Crohn's disease who was found to have aggressive metastatic colon cancer. The patient had been receiving HGH therapy for anti-aging purposes for 7 years before presentation. Normal and malignant colonic tissue was examined for qualitative and quantitative molecular profiles of growth hormone (GH) and its signaling molecules, using immunohistochemistry and RNA extraction with polymerase chain reaction amplification. RESULTS: Immunoreactivity was more robust in tumor tissue than in normal colon for insulin-like growth factor-1 receptor (IGF-1R) but not for IGF, GH, or GH receptor. RNA extraction with quantitative polymerase chain reaction showed that IGF-1R and vascular endothelial growth factor expression, but not IGF-1, GH receptor, or suppressor of cytokine signaling-2, were higher in tumor than in normal colonic tissue. CONCLUSIONS: Colorectal cancer development concurrent with administration of HGH for anti-aging purposes occurred in an individual already at increased risk for colon cancer. This underscores the need for further investigation of the proneoplastic potential of GH supplementation for anti-aging.

Preoperative Ustekinumab Treatment Is Not Associated With Increased Postoperative Complications in Crohn's Disease: A Canadian Multi-Centre Observational Cohort Study.

BACKGROUND: Ustekinumab (UST), an anti-IL12/23 inhibitor is indicated for moderate-to-severe Crohn's disease (CD). However, it is unclear if patients treated with UST are at increased risk for postoperative complications. AIM: To evaluate the postoperative safety outcomes in UST-treated CD patients. METHODS: A multicentre cohort study of UST-treated CD patients at two tertiary care centres (University of Calgary, University of Alberta, Canada) undergoing abdominal surgery between 2009 and 2016 was performed. Postoperative outcomes were compared against a control cohort of anti-TNF-treated patients over the same time-period. The primary outcome was occurrence of postoperative complications up to six months postoperatively, stratified by timing (early <30 days vs. late complications ≥30 days). RESULTS: Twenty UST-treated patients and 40 anti-TNF-treated patients were included with a median preoperative treatment exposure of 6.5 months and 18 months, respectively (p=0.01). Bowel obstruction was the most common surgical indication in both cohorts. UST-treated patients were more likely to require an ostomy (70.0% vs. 12.5%, p<0.001) and be on combination therapy with either systemic corticosteroids or concurrent immunomodulators (azathioprine or methotrexate) (25.0% vs. 2.5%, p=0.01). Despite the increased concomitant use of immunosuppression in the UST-treated cohort, there were no significant differences in early or late postoperative wound infections (1/20 in UST-cohort, 2/40 in anti-TNF cohort, p=1.00), anastomotic leak (0/20 in UST-cohort, 3/40 in anti-TNF cohort, p=0.54), or postoperative ileus/obstruction (3/20 in UST-cohort, 4/40 in anti-TNF cohort, p=0.67). CONCLUSIONS: CD patients receiving preoperative UST did not experience an increase in postoperative complications, despite increased use of concurrent immunosuppression.