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The value of ustekinumab (UST) therapeutic drug monitoring (TDM) in clinical practice remains unclear. This study examined the impact of UST TDM on clinical decision making in patients with Crohn’s disease (CD). A total of 110 consecutive UST-treated CD patients were enrolled in this multicenter, single-arm cross-sectional study. During a single study visit, clinical decisions, disease characteristics, and serum and fecal samples were obtained. The primary outcome was congruency of the actual and two hypothetical clinical decisions based on provision of UST TDM (with and without fecal calprotectin [FCP]) to participating clinicians. Decisions were compared against those of a review panel. A sub-study retrospectively measured the associations of clinical outcomes at the next follow-up visit with serum UST concentration [UST]. No differences in the pattern of decisions by clinicians were observed before and after provision of UST TDM (P = 1.0) or UST TDM + FCP (P = 0.86). However, 39% (TDM) and 50% (TDM + FCP) of hypothetical decisions differed from the initial decisions. The review panel’s decisions differed with the addition of TDM + FCP (P = 0.0006), but not TDM alone (P = 0.16). The sub-study (n = 53) failed to detect an association between therapeutic serum [UST] at the initial study visit and clinical outcomes at the next visit. In consecutive CD patients treated with UST, the addition of TDM into routine clinical practice did not significantly impact clinical decisions and there was no association between short-term clinical outcomes and serum [UST]. Further studies are warranted before clinicians routinely implement UST TDM into clinical practice.

Adalimumab and golimumab are subcutaneously administered anti-tumor necrosis factor α (TNFα) biologics used in the treatment of ulcerative colitis (UC). To date, no studies have directly compared treatment patterns and healthcare resource utilization (HRU) among patients with UC receiving these therapies in a real-world setting. The objective of this study was to compare these outcomes among patients with UC treated with either adalimumab or golimumab using a US claims database. Patients with UC treated with golimumab or adalimumab were identified using the US Optum Clinformatics® Data Mart database. Outcomes of interest included treatment patterns (discontinuations, dose optimizations, persistence, and concomitant medication use) and HRU (outpatient office visits, emergency room [ER] visits, and inpatient stays). Propensity score matching (PSM) was used to account for differences in confounding variables between groups. Overall, 990 patients were identified (golimumab: n = 277; adalimumab: n = 713). After PSM, 246 patients were included in each group. There were no significant differences between the adalimumab and golimumab groups over the full follow-up period in terms of treatment discontinuations (53.7% vs. 51.2%; P = 0.5881), dose optimizations (35.4% vs. 39.4%; P = 0.3515), or persistence (338.2 vs. 361.2 days; P = 0.4194). During the year after initiating therapy, there were no significant differences in concomitant immunosuppressant (21.9% vs. 21.7%; P = 0.9686) or corticosteroid use (74.7% vs. 78.8%; P = 0.3573) or in HRU outcomes including outpatient office visits (93.3% vs. 94.0%; P = 0.7660), ER visits (15.2% vs. 10.9%; P = 0.2238), and inpatient stays (15.2% vs. 13.6%; P = 0.6680). In this nationwide PSM cohort study of patients with UC receiving golimumab or adalimumab, no significant differences were observed between groups for treatment patterns or HRU outcomes. High rates of concomitant corticosteroid use, treatment discontinuations, and HRU while on therapy highlight key unmet needs in the treatment of UC.

A hegemon can destroy its international regimes, but what happens when it does not possess the capacity to reconstitute a regime to its liking? Drawing on structural power theory, our article examines President Nixon’s historic attacks on the Bretton Woods international monetary regime to help illuminate President Trump’s attacks on the World Trade Organisation (WTO). In both cases regime destruction was driven to a large extent by a desire to contain rivals: Europe for Nixon, China for Trump. Drawing on original archival material, our case study analysis shows that while the United States possessed sufficient negative structural power to derail Bretton Woods, it lacked sufficient positive structural power to create the new monetary structure Nixon wanted. Trump faces a similar dilemma: he can block the WTO regime, but cannot necessarily replace it with one to the United States’ liking. China is too powerful and possesses too much structural power of its own to give up its WTO privileges without a fight. After the Coronavirus pandemic, it is unlikely that China can prevent the United States from wrecking the WTO trade regime, but very likely it can block US attempts to create a successor regime tailored exclusively to US requirements.

Adalimumab and golimumab are subcutaneously administered anti-tumor necrosis factor α (TNFα) biologics used in the treatment of ulcerative colitis (UC). To date, no studies have directly compared treatment patterns and healthcare resource utilization (HRU) among patients with UC receiving these therapies in a real-world setting. The objective of this study was to compare these outcomes among patients with UC treated with either adalimumab or golimumab using a US claims database.Patients with UC treated with golimumab or adalimumab were identified using the US Optum ClinformaticsOverall, 990 patients were identified (golimumab: n = 277; adalimumab: n = 713). After PSM, 246 patients were included in each group. There were no significant differences between the adalimumab and golimumab groups over the full follow-up period in terms of treatment discontinuations (53.7% vs. 51.2%; P = 0.5881), dose optimizations (35.4% vs. 39.4%; P = 0.3515), or persistence (338.2 vs. 361.2 days; P = 0.4194). During the year after initiating therapy, there were no significant differences in concomitant immunosuppressant (21.9% vs. 21.7%; P = 0.9686) or corticosteroid use (74.7% vs. 78.8%; P = 0.3573) or in HRU outcomes including outpatient office visits (93.3% vs. 94.0%; P = 0.7660), ER visits (15.2% vs. 10.9%; P = 0.2238), and inpatient stays (15.2% vs. 13.6%; P = 0.6680).In this nationwide PSM cohort study of patients with UC receiving golimumab or adalimumab, no significant differences were observed between groups for treatment patterns or HRU outcomes. High rates of concomitant corticosteroid use, treatment discontinuations, and HRU while on therapy highlight key unmet needs in the treatment of UC.

Background The efficacy of golimumab to induce and maintain remission in biologic-naïve patients with ulcerative colitis (UC) is established from placebo-controlled trials. However, golimumab’s real-world effectiveness, important to physicians and payers, remains unexplored. Aim The goal of this study was to describe real-world use and rate of persistence among UC patients with golimumab therapy and to assess factors that predict discontinuation during golimumab maintenance treatment. Methods A retrospective study of UC patients receiving golimumab maintenance therapy (August 2012–August 2015) was conducted on dosing data from a national case management program. Treatment persistence, defined as time from index prescription to the last dose (gap in dose >60 days), was assessed using Kaplan-Meier survival analysis. Predictors of treatment persistence were explored with Cox proportional hazards regression. Results One hundred thirty-six patients (50.7% male) with a mean (SD) age of 44.4 (15.6) years were included. At golimumab initiation, 72.1% were naïve to anti-TNFs; 77.2% received 200 mg, while 4.4% and 18.4% received 50 mg and 100 mg, respectively, every 4 weeks (induction therapy). The median time to discontinuation was 530 days, with a cumulative probability of 63% to remain on therapy at one year. Age, gender, golimumab induction, golimumab maintenance dose and prior anti-TNF exposure were not significantly associated with treatment persistence. Dose adjustment occurred in 7.4% of patients during maintenance treatment. Conclusions Overall, the persistence rate of golimumab observed in the current real-world study is similar to that described in previous single-centre UC cohorts and consistent with that seen in controlled clinical trials.

Background Therapeutic drug monitoring is an important adjunct in optimising IBD management in patients treated with anti-TNF therapies. However, it remains unclear whether these principles apply to non-anti-TNF biologic therapies, such as the anti-IL12/23 agent, ustekinumab (UST). A follow-up analysis of the ‘mUST-DECIDE’ study explores the correlation between UST drug level and clinical outcomes. Methods 111 consecutive UST-treated adult CD patients across 11 sites in Canada from April 2017 to January 2018 were evaluated. Clinical decisions were recorded for all subjects at the single study visit and blood was drawn for TDM (Sanquin, radioimmunoassay). A retrospective chart review was completed in patients who had a follow-up visit ≥ 30 days after the baseline visit. Improved disease control (primary outcome) was defined as a composite assessment outcome meeting ≥ 1 disease control criterion (symptomatic, endoscopic/imaging, biochemical) without any of the non-response criteria (inadequate or loss of response, worsening of any disease control criteria, initiation of any CD-related medications and adverse events). Serum [UST] were categorised as therapeutic, subtherapeutic or uninterpretable based on their position in a 2 compartment PK model [subjects on Q8W dosing were assessed as per the log-linear model which projected a therapeutic level of ≥4.5 µg/ml at 4 weeks and ≥1.0 µg/ml at 8 weeks]. Results 53 patients had a clinical follow-up visit and an interpretable serum [UST]. Patients had refractory disease (89% anti-TNF-exposed, median 16.4 years since diagnosis), but clinically well (66% had baseline HBI Conclusion The sub-study did not detect any association between routine serum [UST] and short-term clinical outcomes at the next patient visit. These data broadly suggests that the routine measurement of serum UST in CD patients does not aid in disease management, though further studies across different clinical scenarios (e.g. loss of response) are warranted.

James C Gregor,1 Martin Williamson,2 Dorota Dajnowiec,2 Bernie Sattin,2 Erik Sabot,3 Baljinder Salh4 1Division of Gastroenterology, Department of Medicine, Western University, London, ON, Canada; 2Janssen Inc., Toronto, ON, Canada; 3OptumInsight, Boston, MA, USA; 4Division of Gastroenterology, Department of Medicine, University of British Columbia, Vancouver, BC, Canada Background: Given the large armamentarium of therapies for inflammatory bowel disease (IBD), physicians cannot fully describe all treatments to patients and, therefore, make assumptions regarding treatment attributes communicated to patients. This study aimed to assess out-of-pocket willingness-to-pay that IBD patients allocate to treatment attributes.Methods: Adult patients receiving therapy for IBD were invited to access a cross-sectional web-based discrete-choice experiment (May 22–August 31, 2015) that presented paired medication scenarios with varying efficacy, safety, and administration parameters. Preference weights and willingness-to-pay for each attribute level were assessed by a hierarchical Bayes method including a multinomial logit model.Results: A total of 586 IBD patients were included, 404 (68.9%) with Crohn’s disease and 182 (31.1%) with ulcerative colitis. Genders were evenly distributed; the majority of patients (70.1%) were 50 years or younger and had postsecondary education (75.4%), while the median health status was 7 (Likert scale: 1 [poor] – 10 [perfect]). Regarding relative preference-weight estimates, for the average respondent, reducing pain during administration, mucosal healing, and symptom relief were the highest-ranking attributes. Conversely, infusion reactions and risk of hospitalization or surgery were the lowest-ranking attributes. In multivariate analysis, patient sociodemographics did not affect the rank order of attributes although small differences were observed between asymptomatic and symptomatic patients in the previous year.Conclusion: This study has important implications related to understanding patient preferences and designing patient-centered strategies. IBD patients prioritize treatments with low administration pain. Additionally, these results concur with treatment guidelines emphasizing patients’ preference for mucosal healing and symptom control. Keywords: inflammatory bowel disease, patient preference, willingness-to-pay, discrete choice

Canadian inflammatory bowel disease patients treated with infliximab are predominantly managed through a nationwide case management system, named BioAdvance(®).A web-based survey was provided to patients currently receiving infliximab therapy within BioAdvance(®). Patients were categorized according to health trajectories: decliners, non-changers, moderate increasers and strong increasers. Factors associated with health trajectories were identified using multivariable multinomial logistic regression.918 of 1160 respondents were inflammatory bowel disease patients reporting health status. Strong increasers were more likely to use educational tools than non-changers (adjusted odds ratio [aOR]: 1.65; 95% CI: 1.03-2.64), to be treated for ulcerative colitis (aOR: 2.05; 95% CI: 1.16-3.64) and to perceive case management as important (aOR: 2.52; 95% CI: 1.56-4.09). Younger (aOR: 0.72; 95% CI: 0.63-0.83) and French-speaking (aOR: 0.34; 95% CI: 0.18-0.63) patients were less likely to miss workdays. Patients were more likely to have missed workdays prior to joining the case management program.Inflammatory bowel disease patients receiving infliximab within the nationwide case management system report a positive impact on health status and absenteeism.

To understand the perception of intravenous infusions in patients receiving infliximab (Remicade) within the BioAdvance patient support program (PSP).Intravenous infusion of infliximab occurs at approximately 200 clinics across Canada and is managed via the BioAdvance PSP. Patients were invited to complete a 28-question survey on demographics, disease/treatment characteristics, health rating, lifestyle, employment, and perception of intravenous infusions and the BioAdvance program.Analyses were exploratory and descriptive; collected data were self-reported ordinal (Likert scale, unfavorable-to-favorable, 1-10). The Wilcoxon signed-rank test was used to assess statistical significance, and multinomial logistic regression identified predictors of a positive perception of intravenous infusions.1,712 patients completed the survey. Most respondents had been treated with infliximab for2 years (58%), had not been previously treated with a biologic (74%), and were receiving treatment for inflammatory bowel disease (76%). Sixty-two percent of patients were employed and most traveled for personal/work reasons (57%) and had a busy/active lifestyle (76%) while attending the BioAdvance clinics. Before treatment, participants rated their perceived favorability of intravenous infusions at 5/10 (median; interquartile range, 5-7); after multiple infusions, their rating increased significantly to 8 (7-9) (P.001). Regression analysis identified four predictors of a positive infusion experience: French language, favorable ratings of health, accuracy of physician's description, and satisfaction with their BioAdvance coordinator. The vast majority of participants were likely to recommend the BioAdvance PSP.The survey results indicate that the majority of patients receiving infliximab have a positive infusion experience within the BioAdvance PSP.

Testosterone contributes to sex differences in hypothalamic–pituitary–adrenal (HPA) function in humans and rodents, but the central organization of this regulation remains unclear. The medial preoptic nucleus (MPN) stands out as an important candidate in this regard because it contains androgen receptors and projects to forebrain nuclei integrating cognitive–affective information and regulating HPA responses to homeostatic threat. These include the HPA effector neurons of the paraventricular nucleus (PVN) of the hypothalamus, medial amygdala, and lateral septum. To test the extent to which androgen receptors in the MPN engage these cell groups, we compared in adult male rats the effects of unilateral microimplants of testosterone and the androgen receptor antagonist hydroxyflutamide into the MPN on acute restraint induced activation and/or neuropeptide expression levels. The basic effects of these implants were lateralized to the sides of the nuclei ipsilateral to the implants. Testosterone, but not hydroxyflutamide implants, decreased stress-induced Fos and arginine vasopressin (AVP) heteronuclear RNA expression in the PVN, as well as Fos expression in the lateral septum. In unstressed animals, AVP mRNA expression in the PVN decreased and increased in response to testosterone and hydroxflutamide MPN implants, respectively. The differential influences of these implants on AVP mRNA expression were opposite in the medial amygdala. These results confirm a role for androgen receptors in the MPN to concurrently modulate neuropeptide expression and activational responses in the PVN and its extended circuitries. This suggests that the MPN is capable of bridging converging limbic influences to the HPA axis with changes in gonadal status.

Previous data have consistently demonstrated an inhibitory effect of androgens on stress-induced hypothalamic-pituitary-adrenal (HPA) responses. Several brain regions may influence androgen-mediated inhibition of the HPA axis, including the medial preoptic area. To test the role of the medial preoptic nucleus (MPN) specifically, we examined in high- and low-testosterone-replaced gonadectomized rats bearing discrete bilateral lesions of the MPN basal and stress-induced indexes of HPA function, and the relative levels of corticotropin-releasing hormone (CRH) and arginine vasopressin (AVP) mRNA in the amygdala. High testosterone replacement decreased plasma adrenocorticotropin hormone (ACTH) and paraventricular nucleus (PVN) Fos responses to restraint exposure in sham- but not in MPN-lesioned animals. AVP-, but not CRH-immunoreactivity staining in the external zone of the median eminence was increased by testosterone in sham animals, and MPN lesions blocked this increment in AVP. A similar interaction between MPN lesions and testosterone occurred on AVP mRNA levels in the medial nucleus of the amygdala. These findings support an involvement of MPN projections in mediating the AVP response to testosterone in both the medial parvocellular PVN and medial amygdala. We conclude that the MPN forms part of an integral circuit that mediates the central effects of gonadal status on neuroendocrine and central stress responses.

Myzus persicae nicotianae is an important pest in Greece, controlled mainly by neonicotinoids. Monitoring of the aphid populations for resistance mechanisms is essential for effective control.Two new RFLP-based diagnostics for the detection of the M918T (super-kdr pyrethroid resistance) and nAChR R81T (neonicotinoid resistance) mutations were applied, along with other established assays, on 131 nicotianae multilocus genotypes (MLGs) collected from tobacco and peach in Greece in 2012-2013. Furthermore, we present resistance data from aphid clones (500, mainly nicotianae) collected in 2006-2007. About half of the clones tested with a diagnostic dose of imidacloprid were tolerant. The R81T mutation was not found in the 131 MLGs and 152 clones examined. Over half (58.6%) of a subset of 29 clones showed a 9-36-fold overexpression of CYP6CY3. M918T was found at low to moderate frequencies. The kdr and MACE mechanisms and carboxylesterase-based resistance were found at high frequency in all years.The aphid retains costly resistance mechanisms even in the absence of pressure from certain insecticides, which could be attributed to factors related to climate and genetic properties of the populations. The indication of build-up of resistance/tolerance to neonicotinoids, related to CYP6CY3 overexpression, is a matter of concern. © 2015 Society of Chemical Industry.

Despite clear evidence of the potency by which sex steroids operate on the hypothalamic-pituitary-adrenal (HPA) axis and genuine sex differences in disorders related to HPA dysfunction, the biological significance of this remains largely ignored. Stress-induced increases in circulating glucocorticoid levels serve to meet the metabolic demands of homeostatic threat head-on. Thus, the nature of the stress-adrenal axis is to protect the organism. As one develops, matures, and ages, still newer and competing physiological and environmental demands are encountered. These changing constraints are also met by shifts in sex steroid release, placing this class of steroids beyond the traditional realm of reproductive function. Here we focus on the dose-related and glucocorticoid-interactive nature by which testosterone operates on stress-induced HPA activation. This provides an overview on how to exploit these characteristics towards developing an anatomical framework of testosterone's actions in the brain, and expands upon the idea that centrally projecting arginine vasopressin circuits in the brain act to register and couple testosterone's effects on neuroendocrine and behavioural responses to stress. More generally, the work presented here underscores how a dual adrenal and gonadal systems approach assist in unmasking the bases by which individuals resist or succumb to stress.

Laser driven flyers are produced on the interaction of a laser pulse with a thin film of metal. When an Nd:YAG laser is focussed through a transparent substrate onto a 5 micron film of aluminium, a fraction of the metal is ablated. The associated expansion causes the remaining aluminium to be punched from the film and launched as a discrete flyer. Due to the high reflectivity of aluminium, some of the laser energy is lost through reflection at the substrate/metal boundary. By introducing metals which exhibit stronger absorption at the Nd:YAG wavelength (1.064 μm), the laser coupling to the flyer should be improved, resulting in faster flyer velocities for a given pulse energy. This paper discusses the results of using Hf, Ge, Zn and Ti to improve the coupling of the Nd:YAG laser to the flyer.

Largely ignored in tests of defensive burying is the capacity for individual animals to display marked variations in active coping behaviors. To expose the neurobiological correlates of this behavioral differentiation rats were exposed to a mousetrap that was remotely triggered upon approach to remove the quality of pain. Relative to animals showing no significant levels of defensive burying activity, rats showing sustained elevations in defensive burying displayed higher levels of arginine vasopressin (AVP) mRNA and increased numbers of androgen receptor positive cells in the medial amygdala and posterior bed nuclei of the stria terminalis, brain regions that integrate emotional appraisal and sensory information. In contrast, animals showing little to no defensive burying responses displayed relatively higher levels of AVP and oxytocin (OT) mRNA within the supraoptic nucleus and subregions of the paraventricular nucleus of the hypothalamus responsible for neuroendocrine and autonomic function. Finally, animals showing sustained levels of burying also displayed increased levels of testosterone and pituitary-adrenal hormones under stress conditions. These findings implicate roles for central AVP and OT in mediating differential avoidance behaviors and demonstrate the utility of using a pain-free test of defensive burying as a framework for exploring naturally occurring differences in coping style and neuroendocrine capacity.

Androgen receptors are distributed throughout the central nervous system and are contained by a variety of nuclei that are known to project to or regulate the paraventricular nucleus (PVN) of the hypothalamus, the final common pathway by which the brain regulates the hypothalamic-pituitary-adrenal (HPA) response to homeostatic threat. Here we characterized androgen receptor staining within cells identified as projecting to the PVN in male rats bearing iontophoretic or crystalline injections of the retrograde tracer FluoroGold aimed at the caudal two-thirds of the nucleus, where corticotropin-releasing hormone-expressing neurons are amassed. Androgen receptor (AR) and FluoroGold (FG) double labeling was revealed throughout the limbic forebrain, including scattered numbers of cells within the anterior and posterior subdivisions of the bed nuclei of the stria terminalis; the medial zone of the hypothalamus, including large numbers of AR-FG-positive cells within the anteroventral periventricular and medial preoptic cell groups. Strong and consistent colabeling was also revealed throughout the hindbrain, predominantly within the periaqueductal gray and the lateral parabrachial nucleus, and within various medullary cell groups identified as catecholaminergic, predominantly C1 and A1 neurons of the ventral medulla. These connectional data predict that androgens can act on a large assortment of multimodal inputs to the PVN, including those involved with the processing of various types of sensory and limbic information, and provide an anatomical framework for understanding how gonadal status could contribute to individual differences in HPA function.

Activation of the hypothalamic-pituitary-adrenal (HPA) axis is initiated by neurosecretory neurons residing within the medial parvicellular part of the hypothalamic paraventricular nucleus (PVN). Despite the potency by which sex steroids operate on HPA and medial parvocellular responses to stress, previous topographic and phenotypic studies suggest that gonadal steroid hormone receptors are scarcely, if at all, expressed by PVN neurons controlling anterior pituitary corticotropes. Guided by the pattern of retrograde accumulation of fluorogold, we used a direct connectional approach to define the distribution of androgen receptors (AR) and estrogen-beta receptors (ER-beta) within populations of neurosecretory vs. nonneurosecretory neurons in the PVN. Juxtaposition of AR-immunoreactivity (ir) and ER-beta mRNA to the pattern of intravenous fluorogold labeling showed these steroid hormone receptors to be concentrated within portions of the PVN devoid of neurosecretory neurons. Superimposing receptor profiles onto the pattern of spinal retrograde labeling confirmed a selective distribution of AR-ir within autonomic-related cells of the medial parvocellular division, including its dorsal, lateral, and ventral medial components. ER-beta mRNA expression was likewise concentrated within regions accumulating spinal tracer, highest within the ventral aspect of the PVN. These results indicate a direct influence of gonadal hormones on preautonomic effector neurons and remain in keeping with an indirect influence of androgens on adrenocorticotropin-regulating neurons in the PVN.

This paper presents a study of the sensitivities of calculated doses to the skin, ocular lens of the eye and bone marrow, for crewmembers in low Earth orbit, to variations in solar energetic particle event fluence levels and spectral hardness, spacecraft orbital inclination, geomagnetic field storm levels (Kp index), and spacecraft shielding thickness. In general, doses increase for higher inclination orbits, for higher Kp indices, and for harder SPE spectra. The predicted doses sometimes change dramatically for even small variations in the assumed conditions. For large events in high inclination orbits, with a highly disturbed geomagnetic field, doses can be very hazardous to crews.

The purpose of this research project is to develop compact (100 to 400 MWe) Generation IV nuclear power plant design and layout concepts that maximize the benefits of factory-based fabrication and optimal packaging, transportation and siting. The reactor concepts selected were compact designs under development in the 2000 to 2001 period. This interdisciplinary project was comprised of three university-led nuclear engineering teams identified by reactor coolant type (water, gas, and liquid metal) and a fourth Industrial Engineering team. The reactors included a Modular Pebble Bed helium-cooled concept being developed at MIT, the IRIS water-cooled concept being developed by a team led by Westinghouse Electric Company, and a Lead-Bismuth-cooled concept developed by UT. In addition to the design and layout concepts this report includes a section on heat exchanger manufacturing simulations and a section on construction and cost impacts of proposed modular designs.

Introduction: Chronic granulomatous disease (CGD) is an immunodeficiency syndrome caused by a defective NADPH oxidase complex. Afflicted patients are unable to produce adequate reactive oxygen metabolites to neutralize microorganisms within macrophages. Approximately 50% of CGD patients develop gastrointestinal (GI) disease that shares features of both Crohn's disease and ulcerative colitis. In patients with pediatric-onset ulcerative colitis, the cumulative risk for colorectal cancer (CRC) is 2% at 10 years (yrs) and 8% at 20 yrs. While the increased risk of CRC among patients with longstanding inflammatory bowel disease (IBD) is well established, the incidence of CRC among CGD patients with longstanding colitis has not been described. Methods: Patients with CGD colitis were identified from a database comprised of 279 CGD patients seen at the NIH from 1972 to 2011. To allow for adequate endoscopic, pathologic, and clinical follow-up, 78 patients with evidence of CGD colitis seen between 1990 and 2010 were identified, and patients with disease duration >10 yrs were used for formal analysis. The clinical and endoscopic reports over the 10 year follow-up period were reviewed, and the colonic biopsies were reexamined when available. Demographic information, duration of disease, endoscopic findings, and treatment and surgical history were extracted from the electronic medical records. The primary endpoint was the evidence of dysplasia or development of CRC. Results: Of the 78 patients, 20 had disease for >10 yrs. Notably, no colonic dysplasia or CRC were seen at the time of the biopsies in any of these patients. Of the 20 patients with disease > 10 yrs, 8 had biopsies available for formal reexamination. On reexamination, no patients were found to have colonic dysplasia or CRC. For all 20 patients, the average age at diagnosis was 10 years, with the median duration of disease of 16.7 yrs. Polyps were noted in 5 of 20 patients, 3 of which were inflammatory, 1 hyperplastic and 1 normal mucosa. No patients were diagnosed with colorectal cancer during follow-up. Conclusions: Despite long-standing inflammation, there was no dysplasia or CRC among 20 patients with CGD after a median of 16.7 years of follow up. In addition, no cases of colonic dysplasia or CRC were found in any patients with CGD colitis. The incidence of CRC among patients with CGD colitis appears to be lower than the incidence among patients with IBD. In fact, there are no reported cases of malignant polyps, dysplasia, or any gastrointestinal cancers in the short term or long term data. Although limited by a retrospective study design, these data suggest that the development of CRC in the setting of chronic inflammation may be influenced by NADPH activity, suggesting superoxide metabolism as a possible target to prevent oncogenesis.