Supplementary Table 2 from Identification of Genes Differentially Expressed in Benign versus Malignant Thyroid Tumors

Supplementary Figure 1 from Identification of Genes Differentially Expressed in Benign versus Malignant Thyroid Tumors

Laryngopharyngeal reflux (LPR) is a common otolaryngologic diagnosis. Treatment of presumed LPR remains challenging, and limited frameworks exist to guide treatment. Using RAND/University of California, Los Angeles (UCLA) Appropriateness Methods, a modified Delphi approach identified consensus statements to guide LPR treatment. Experts independently and blindly scored proposed statements on importance, scientific acceptability, usability, and feasibility in a four-round iterative process. Accepted measures reached scores with ≥ 80

Background: In inflammatory bowel disease (IBD), many scenarios call for fecal diversion, leaving behind defunctionalized bowel. The theoretical risk of colorectal cancer (CRC) in this segment is frequently cited as a reason for resection. To date, no studies have characterized the incidence of neoplasia in the diverted colorectal segments of IBD patients. Methods: A retrospective cohort analysis was conducted for IBD patients identified through a tertiary care center pathology database. Patients that had undergone colorectal diversion and were diverted for >= 1 year were included. Incidence of diverted dysplasia/CRC was calculated for Crohn's disease (CD) and ulcerative colitis (UC) with respect to diverted patient-years (dpy) and patient-years of disease (pyd). Results: In total, 154 patients comprising 754 dpy and 1984 pyd were analyzed. Only 2 cases of diverted colorectal dysplasia (CD 1, UC 1) and 1 case of diverted CRC (UC) were observed. In the UC cohort (n = 75), the rate of diversion-associated CRC was 4.5 cases/1000 dpy (95% CI 0.11-25/1000) or 1.5 cases/1000 pyd (95% CI 0.04-8.2/1000). In the CD cohort (n = 79), no patients developed CRC, although a dysplasia rate of 1.9 cases/1000 dpy (95% CI 0.05-11/1000) or 0.77 cases/1000 pyd (95% CI 0.02-4.3/1000) was observed. All patients developing neoplasia had disease duration > 10 years and microscopic inflammation. Conclusions: Diverted dysplasia occurred infrequently with rates overlapping those reported in registries for IBD-based rectal cancers. Neoplasia was undetected in patients with < 10 pyd, regardless of diversion duration, suggesting low yield for endoscopic surveillance before this time.

The demonstration of competency in endoscopy is required prior to obtaining American Board of Surgery Certification. To demonstrate competency, the resident must pass a national high-stakes cognitive test and a technical skills exam on a virtual reality simulator. The purpose of this preliminary study was to design a proficiency-based endoscopy simulation curriculum to meet this competency requirement.

Aim Few data are available on the optimal long-term care of early-stage colorectal cancer survivors, termed survivorship care. We aimed to investigate current practice in the management of patients following treatment for early-stage colorectal cancer. Method Results We performed an internet survey of members of the American Society for Colon and Rectal Surgeons about several aspects of long-term care, including allocation of clinician responsibility, challenges with transitions to primary care physicians (PCPs), long-term care plan provision and recommended surgical follow-up duration. Overall, 251 surgeons responded. Surgeons reported taking primary responsibility for managing adverse surgical effects (93.2%) and surveillance testing (imaging and laboratories 68.6%, endoscopy 82.4%). Barriers to PCP handoffs included patient preference for surgical follow-up (endorsed by 76.6%) and inadequate communication with PCPs (endorsed by 36.9%). Approximately one-third of surgeons routinely provide survivorship care plans to PCPs; surgeons who received formal survivorship training were more likely to do so compared to those without such training (OR 3.29, 95% CI 1.57, 6.92). Although only 20.4% of surgeons follow their patients beyond 5 years, individuals in practice longer were more likely to continue long-term follow-up than those with <= 10 years of experience. Conclusions This is the largest survey of surgeons regarding long-term management for early-stage colorectal cancer and highlights the potential for improved coordination with PCPs and increased implementation of survivorship care plans.

It is unclear whether intensive surveillance protocols have resulted in a decreased incidence of colorectal cancer (CRC) in inflammatory bowel disease (IBD).To determine the prevalence and characteristics of IBD associated high-grade dysplasia (HGD) or CRC that was undetected on prior colonoscopy.This is a single-center, retrospective study from 1994 to 2013. All participants had a confirmed IBD diagnosis and underwent a colectomy with either HGD or CRC found in the colectomy specimen.The undetected group had no HGD or CRC on prior colonoscopies. The detected group had HGD or CRC identified on previous biopsies.Of 70 participants, with ulcerative colitis (UC) (n = 47), Crohn's disease (CD) (n = 21), and indeterminate colitis (n = 2), 29% (n = 20) had undetected HGD/CRC at colectomy (15 HGD and 5 CRC). In the undetected group, 75% had prior LGD, 15% had indefinite dysplasia, and 10% had no dysplasia (HGD was found in colonic strictures). Patients in the undetected group were more likely to have pancolitis (55 vs. 20%) and multifocal dysplasia (35 vs. 8%). The undetected group was less likely to have CRC at colectomy (25 vs. 62%). There was a trend toward right-sided HGD/CRC at colectomy (40 vs. 20%; p = 0.08). In addition, 84% of the lesions found in the rectum at colectomy were not seen on prior colonoscopy in the undetected group.The prevalence of previously undetected HGD/CRC in IBD found at colectomy was 29%. The high proportion of undetected rectal and right-sided HGD/CRC suggests that these areas may need greater attention during surveillance.

Background: Creation of a J pouch is the gold standard surgical intervention in the treatment of chronic ulcerative colitis (UC). Pouchoscopy prior to ileostomy takedown is commonly performed. We describe the frequency, indication, and findings on pouchoscopy, and determine if pouchoscopy affects rates of complications after takedown. Methods: All UC or indeterminate inflammatory bowel disease patients with a J pouch were retrospectively evaluated from January 1994 to December 2014. Cases were defined as having routine (asymptomatic) pouchoscopy after pouch creation but before ileostomy takedown. Controls were defined as having no pouchoscopy or pouchoscopy on the same day as that of takedown. Results: The study included 178 patients (81.5% cases, 18.5% controls). Fifty two percent of pouchoscopies were reported as normal. Common abnormal endoscopy findings included stricture (35%), pouchitis (7%), and cuffitis (0.7%). Length of stay during takedown hospitalization was shorter for cases than controls (3 vs. 5 days; p = 0.001), but neither short- nor long-term complications were statistically different between cases and controls. Abnormalities on pouchoscopy were not predictive for short-term complications (p = 0.73) or long-term complications (p = 0.55). Routine pouchoscopy did not delay takedown surgery in any of the included patients. Conclusions: Routine pouchoscopy may not be necessary prior to ileostomy takedown; its greatest utility is in patients with suspected pouch complications.

BACKGROUND AND AIMS:NLRP3 inflammasome is known to be involved in inflammatory bowel diseases. However, it is controversial whether it is pathogenic or beneficial. This study evaluated the roles of NLRP3 inflammasome in the pathogenesis of inflammatory bowel disease in IL-10-/- mice and humans.METHODS:NLRP3 inflammasome in colonic mucosa, macrophages, and colonic epithelial cells were analysed by western blotting. The NLRP3 inflammasome components were studied by sucrose density gradient fractionation, chemical cross-linking, and co-immunoprecipitation. The role of NLPR3 inflammasome in the pathogenesis of colitis was extensively evaluated in IL-10-/- mice, using a specific NLPR3 inflammasome inhibitor glyburide.RESULTS:NLRP3 inflammasome was upregulated in colonic mucosa of both IL-10-/- mice and Crohn's patients. NLRP3 inflammasome activity in IL-10-/- mice was elevated prior to colitis onset; it progressively increased as disease worsened and peaked as macroscopic disease emerged. NLRP3 inflammasome was found in both intestinal epithelial cells and colonic macrophages, as a large complex with a molecular weight of ≥ 360 kDa in size. In the absence of IL-10, NLRP3 inflammasome was spontaneously active and more robustly responsive when activated by LPS and nigericin. Glyburide markedly suppressed NLRP3 inflammasome expression/activation in IL-10-/- mice, leading to not only alleviation of ongoing colitis but also prevention/delay of disease onset. Glyburide also effectively inhibited the release of proinflammatory cytokines/chemokines by mucosal explants from Crohn's patients.CONCLUSIONS:Abnormal activation of NLRP3 inflammasome plays a major pathogenic role in the development of chronic colitis in IL-10-/- mice and humans. Glyburide, an FDA-approved drug, may have great potential in the management of inflammatory bowel diseases.

BACKGROUND & AIMS: Deep vein thrombosis (DVT) and pulmonary embolism (PE) is associated with prolonged immobility and hospitalization, all of which occur frequently in inflammatory bowel disease (IBD).IBD is a known risk factor for DVT, however the outcomes of DVT in IBD less well described.We examined the impact on clinical care of DVT/PE in patients with IBD.METHODS: We performed a cross-sectional analysis using data collected from the Nationwide Inpatient Sample, from 2012.International Classification of Diseases, 9th revision, Clinical Modification codes were used to identify patients with IBD (ICD-9: 555 &556) andDVT (453.40-42)andPE (415.1).Our primary outcomes were inpatient mortality, length of stay, total charges, and secondary outcomes were acute renal failure, acute respiratory failure and mechanical ventilation in patients with IBD with or without DVT/PE.We used multivariable logistic regression to determine risk factors (age, sex, race, payer, patient residence, hospital size, admission type, admission day, teaching status, bed size, region) that affect mortality, acute renal failure, acute respiratory failure and mechanical ventilation.Linear regression was used to evaluate the effects of DVT/PE on predicted length of stay (LOS) and hospital charges.RESULTS: Patients with IBD and DVT/PE had an increased odds of inpatient mortality [adjusted odds ratio (OR), 3.0; 95% CI (2.15 -4.11)], a longer predicted LOS (11.4 vs 5.4 days; p < 0.001), and greater predicted hospital charges ($100,937.6vs $ 42034.8;p < 0.001), compared to those IBD patients without DVT.Patients with DVT/PE and IBD had increased odds of mechanical ventilation [OR = 2.50; CI 95% (1.89 -3.30)], acute renal failure [OR = 2.0; CI 95% (1.6 -2.5)] and acute respiratory failure [OR = 2.6; CI 95% (2.04 -3.35)].CONCLUSIONS: In patients with IBD, DVT or PE is associated with greater mortality, LOS, charges, acute renal failure and acute respiratory failure and mechanical ventilation.

Recent gene-profiling analyses showed significant upregulation of the folate hydrolase (FOLH1) gene in the affected intestinal mucosa of patients with inflammatory bowel disease (IBD). The FOLH1 gene encodes a type II transmembrane glycoprotein termed glutamate carboxypeptidase II (GCPII). To establish that the previously reported increased gene expression was functional, we quantified the glutamate carboxypeptidase enzymatic activity in 31 surgical specimens and report a robust 2.8- to 41-fold increase in enzymatic activity in the affected intestinal mucosa of IBD patients compared with an uninvolved area in the same patients or intestinal mucosa from healthy controls. Using a human-to-mouse approach, we next showed a similar enzymatic increase in two well-validated IBD murine models and evaluated the therapeutic effect of the potent FOLH1/ GCPII inhibitor 2-phosphonomethyl pentanedioic acid (2-PMPA) (IC50 = 300 pM). In the dextran sodium sulfate (DSS) colitis model, 2-PMPA inhibited the GCPII activity in the colonic mucosa by over 90% and substantially reduced the disease activity. The significance of the target was confirmed in FOLH1-/- mice who exhibited resistance to DSS treatment. In the murine IL-10-/- model of spontaneous colitis, daily 2-PMPA treatment also significantly reduced both macroscopic and microscopic disease severity. These results provide the first evidence of FOLH1/GCPII enzymatic inhibition as a therapeutic option for IBD.

Background: Stenosis is the most common complication of Crohn's disease (CD), often requiring surgical resection.Long-term outcome of patients receiving anti-TNF therapy for such disease complication is poorly known.Methods: 51 CD patients followed-up in a tertiary IBD Center between July 2006 and November 2015 were enrolled.All of them had stricturing CD (Ileal=49, colonic=2), diagnosed by colonoscopy and/or MRI enterography.Thirty-one subjects (61%) were given adalimumab and twenty (39%) infliximab.The primary outcome was the rate of surgery for stricturing CD.Statistical analysis included descriptive analysis, Wilcoxon test for differences in median values, logistic regression with univariate analysis for risk factors, and Kaplan-Meyer curves and Cox analysis for estimation of efficacy of anti-TNFs in avoiding surgical resection.All differences were considered statistically significant for p<0.05.Results: 51 CD patients (27 males; median age at diagnosis 31.9 yrs (range 12-61) were analysed.Median duration of disease at the beginning of anti-TNF therapy was 4.4 yrs (range 0.3-37).The location of CD was ileal in 22 subjects, colonic in one, and ileocolonic in 28 patients.After a median follow-up period of 35.8 months (range 3-105), 20/51 patients (39%) underwent abdominal surgery.Among patients not undergoing surgery, half of them (25/51) continued anti-TNF therapy at last follow-up and 6/51 (11.7%) stopped anti-TNF treatment (1 for secondary loss of response, 1 for infusion reaction, 2 for psoriasis, 1 for pregnancy, and 1 for recurrent tonsillitis).Median values of the Harvey-Bradshaw Index (HBI) and the Simple Endoscopic Score for Crohn's Disease (SES-CD) were reduced significantly from baseline (p=0.01 for both), whereas the median value of the Lémann score did not change significantly (4.9 vs 4.2, p= 0.28).Based on univariate analysis, only penetrating behavior at baseline was more likely to be associated with the risk of surgery (OR 5.09; CI 95% 1.45 to 17.82; p=0.01).Survival curve analysis and Cox regression model showed that patients treated with infliximab were more likely to avoid surgery than adalimumab (HR 3.13, p=0.0038 and OR 6.54; p= 0.0026, respectively).The use of infliximab and longer duration of anti-TNF therapy were protective from surgery (OR 1.05; CI 95% 0.01-0.08;p= 0.0017).Conclusion: Half of CD patients starting anti-TNF therapy for stricturing disease avoided surgery after a median follow-up of 3 years.Penetrating behaviour was associated with an increased risk of surgery.Patients treated with infliximab remained free of surgery longer than patients treated with adalimumab.

Journal of the American College of Surgeons 221(4):p e10, October 2015. | DOI: 10.1016/j.jamcollsurg.2015.08.421

Introduction: Creation of a J pouch is the current gold standard surgical intervention in patients with chronic ulcerative colitis (UC). Pouchoscopy prior to takedown of the loop ileostomy is commonly performed. We aim to describe the frequency, indication, and findings on pouchoscopy, and determine if pouchoscopy affects rates of complications after takedown. Methods: A retrospective chart review of all UC or indeterminate inflammatory bowel disease patients with a J pouch was conducted from Jan 1994-Dec 2014 at a single tertiary hospital. Cases were defined as having a pouchoscopy after J pouch creation but before ileostomy takedown. Controls were defined as having no pouchoscopy or pouchoscopy on the same day as ileostomy takedown. Statistical analysis was performed using STATA. Results: A total of 185 patients were included in the study, of which 152 (82.2%) were cases and 33 (17.8%) were controls. Of the controls, 21 patients (11.4%) had no endoscopy and 12 (6.5%) had pouchoscopy on the same day as ileostomy takedown. One case and one control had undergone J pouch creation but not ileostomy takedown. The most frequent indication for J pouch surgery was medically refractory disease. Cases and controls were similar in baseline characteristics; cases were more likely to have undergone stapled anastomoses and had a shorter duration of follow-up (Table 1). Most pouchoscopies were performed on a routine basis (n=145, 95.4%). Half (n=75) of all pouchoscopies were reported as normal. Common abnormal endoscopy findings included stricture (n=53, 35.3%), pouchitis (n=13, 8.7%), and cuffitis (n=1, 0.7%). All patients with strictures were dilated at the time. Length of stay during ileostomy takedown hospitalization was shorter for cases than controls. However, neither short- nor long-term complications were statistically different between cases and controls (Table 2). Additionally, abnormalities on pouchoscopy were not predictive for either short- (p=0.75) or long-term complications (p=0.57). Pouchoscopy delayed ileostomy takedown surgery in 4 patients, all of whom were symptomatic or had recognized complications prior to pouchoscopy.Table 1: Patient and Surgical CharacteristicsTable 2: Outcome MeasuresConclusion: Pouchoscopy prior to ileostomy takedown was common in our institutional experience. Although rates of abnormalities on pouchoscopy (mostly strictures) were frequent, ileostomy takedown was rarely delayed and there was no association with future complications. Pouchoscopy prior to ileostomy takedown probably has greatest utility in symptomatic patients.

IMPORTANCE Laparoscopic repair of paraesophageal hernia (PEH) has been shown to result in excellent relief of symptoms and improved quality of life (QOL) despite a relatively high radiographically identified recurrence rate.OBJECTIVE To assess potential risk factors for recurrence and long-term change in QOL after laparoscopic repair of PEH.DESIGN, SETTING, AND PARTICIPANTS This was a prospective study of 111 patients who underwent elective laparoscopic repair of type III PEH with biological mesh buttressed over a primary cruroplasty from April 3, 2009, through July 31, 2014, at the Department of Surgery, Johns Hopkins University of Medicine. We administered a modified version of a validated gastroesophageal reflux disease-specific QOL tool to patients before and at 2, 12, and 36 months after the procedure. Higher QOL scores represent greater severity of symptoms. An upper gastrointestinal tract barium-contrast radiographic examination was performed at 1 year to assess for recurrence. Demographic factors, comorbidities, and preoperative radiographic findings were analyzed as possible indicators for recurrence using logistic regression.MAIN OUTCOMES AND MEASURES Quality of life, measured by the gastroesophageal reflux disease-specific QOL tool, and recurrence, defined as a PEH of greater than 2 cm.RESULTS Median patient age was 61 years, 63.1% of patients were women, and 81.1% of patients were white. Four patients required reoperation, of which only 1 was for symptomatic recurrent PEH. The mean follow-up time for the 36-month QOL assessment was 43.5 months. The overall preoperative and 2-, 12-, and 36-month QOL scores were 28.50, 10.18, 9.74, and 10.58, respectively (P <.001). Recurrences were found in 19 of the 70 patients (27%) who completed the 1-year radiographic examination. Compared with baseline, all individual symptoms improved significantly except for early satiety (mean [SD] score, 3.18 [1.88] at baseline vs 2.07 [1.70] at the 36-month follow-up; P =.07), nausea (1.69 [1.63] vs 0.77 [1.25]; P =.08), pain with swallowing (1.06 [1.50] vs 0.53 [0.90]; P =.73), and bloating/gas (3.28 [1.71] vs 2.23 [1.72]; P =.05) at the 36-month QOL assessment. Although not statistically significant, preoperative hernias containing most of the stomach were more likely to recur after repair when compared with those involving gastric cardia and fundus (odds ratio, 3.74 [95% CI, 0.93-15.14]; P =.06).CONCLUSIONS AND RELEVANCE Overall, laparoscopic repair of PEH with biological mesh results in excellent long-term QOL. The cause of recurrence is likely multifactorial and individualized to each patient. Further evaluation of novel techniques and unidentified patient factors is needed.

IMPORTANCE High-dose glucocorticoids (GCs) are routinely given to surgical patients with a history of GC exposure to prevent perioperative acute adrenal insufficiency, but this practice is not well supported. OBJECTIVE To evaluate the variability of perioperative GC dosing among patients with inflammatory bowel disease (IBD) undergoing major abdominal surgery. DESIGN, SETTING, AND PARTICIPANTS This was a retrospective study of 49 patients with IBD undergoing colorectal surgery at a single institution between July 2010 and August 2011. Data on patient comorbidities, intraoperative risk factors, surgical site infections, and 30-day readmission rates were prospectively collected from the National Surgical Quality Improvement Program. Preoperative GC exposure at the time of the index admission and perioperative GC therapy during admission were collected by review of the medical records. Patients were divided into 3 groups at the time of surgery: (1) 1 week or more of prior GC exposure, not receiving maintenance therapy (n = 15); (2) currently receiving budesonide (n = 10); and (3) currently receiving oral prednisone (n = 24). MAIN OUTCOMES AND MEASURES Perioperative GC exposure was the main outcome. Qualitative comparisons of perioperative exposure stratified by preoperative GC exposure were done. A multivariate logistic regression analysis was performed to determine significant differences in surgical site infection and 30-day readmission rates among patients with and without perioperative GC exposure. RESULTS Overall, 38 of 49 patients (78%) received perioperative GCs; intraoperative GCs were administered to 35 of 49 patients (71%), and 33 of 49 patients (67%) received postoperative GCs. Patients received intraoperative and postoperative GCs, respectively, as follows: 8 patients (53%) and 7 (47%) in group 1, 7 (70%) and 3 (30%) in group 2, and 20 (83%) and 23 (96%) in group 3. The median intraoperative GC dose was 100 mg (range, 50-267 mg of hydrocortisone or hydrocortisone equivalent for dexamethasone); the median total postoperative GC dose for the first 5 days after surgery was 485 mg (range, 50-890 mg of hydrocortisone or hydrocortisone equivalent for prednisone). The median duration of postoperative GC administration was 3 days for group 1, 6 days for group 2, and 7 days for group 3. No statistically significant difference in surgical site infection and 30-day readmission rates was detected in the GC exposure vs no-exposure groups. CONCLUSIONS AND RELEVANCE Perioperative GC dosing among patients with IBD undergoing colorectal surgery is highly variable even within a single center. Additional studies are needed to define the risk of postoperative adrenal insufficiency and establish standardized practices for perioperative GC therapy, which may have the benefit of reducing GC overuse.

To better understand the ergonomics of robotic surgery (RS) in terms of physical discomfort or symptoms, factors influencing symptom reporting, and robotic surgery systems (RSS) components to be improved.

BACKGROUND:We conducted this study to investigate how physical and cognitive ergonomic workloads would differ between robotic and laparoscopic surgeries and whether any ergonomic differences would be related to surgeons' robotic surgery skill level. Our hypothesis is that the unique features in robotic surgery will demonstrate skill-related results both in substantially less physical and cognitive workload and uncompromised task performance. METHODS:Thirteen MIS surgeons were recruited for this institutional review board-approved study and divided into three groups based on their robotic surgery experiences: laparoscopy experts with no robotic experience, novices with no or little robotic experience, and robotic experts. Each participant performed six surgical training tasks using traditional laparoscopy and robotic surgery. Physical workload was assessed by using surface electromyography from eight muscles (biceps, triceps, deltoid, trapezius, flexor carpi ulnaris, extensor digitorum, thenar compartment, and erector spinae). Mental workload assessment was conducted using the NASA-TLX. RESULTS:The cumulative muscular workload (CMW) from the biceps and the flexor carpi ulnaris with robotic surgery was significantly lower than with laparoscopy (p < 0.05). Interestingly, the CMW from the trapezius was significantly higher with robotic surgery than with laparoscopy (p < 0.05), but this difference was only observed in laparoscopic experts (LEs) and robotic surgery novices. NASA-TLX analysis showed that both robotic surgery novices and experts expressed lower global workloads with robotic surgery than with laparoscopy, whereas LEs showed higher global workload with robotic surgery (p > 0.05). Robotic surgery experts and novices had significantly higher performance scores with robotic surgery than with laparoscopy (p < 0.05). CONCLUSIONS:This study demonstrated that the physical and cognitive ergonomics with robotic surgery were significantly less challenging. Additionally, several ergonomic components were skill-related. Robotic experts could benefit the most from the ergonomic advantages in robotic surgery. These results emphasize the need for well-structured training and well-defined ergonomics guidelines to maximize the benefits utilizing the robotic surgery.

Abstract IL-10-/- mice spontaneously develop chronic colitis. Our study was to evaluate the role and regulation of NLRP3 inflammasome in colitis of IL-10-/- mice and Crohn’s disease (CD). Two major NLRP3 complex proteins, NLRP3 and ASC, were upregulated in colonic mucosa of both IL-10-/- mice and CD. Importantly, NLRP3 inflammasome in IL-10-/- mice was activated prior to the onset of colitis; it progressively increased as disease worsened, peaking as macroscopic disease emerged. NOD2, a major IBD susceptible gene product, was upregulated only at a later stage of colitis when NLRP3 inflammasome was fully activated. The NLRP3 complex, including NLRP3, ASC and caspase-1, was demonstrated in vivo in colonic mucosa and increased in IL-10-/- mice, using 3 independent approaches (density fractionation, crosslinking, and co-IP). NLRP3 inflammasome activation occurred spontaneously in macrophages of IL-10-/- but not WT mice, and was effectively inhibited by IL-10. Glyburide, an inflammasome inhibitor, suppressed NLRP3 inflammasome expression/activation in IL-10-/- mice, resulting in not only alleviation of preexisting colitis, but also prevention of colitis development when given before disease onset. Thus, spontaneous and persistent activation of NLRP3 inflammasome, which is negatively regulated by IL-10, plays a major pathogenic role in colitis, it functions as a disease initiator whereas NOD2 may act as an accelerator. Inhibitors of the NLRP3 inflammasome may have utility in IBD therapy.