Baseline Clinical Factors Are Associated With Risk of Complications in Crohn's Disease: Appraisal of the American Gastroenterological Association Clinical Care Pathway.

INTRODUCTION: The American Gastroenterological Association (AGA) has compiled risk factors that may be predictive of disease complications in Crohn's disease (CD) and ulcerative colitis (UC). The aim of this study was to evaluate the performance of the AGA risk factors for risk stratification in UC and CD. METHODS: We included participants of 2 cohorts: the Ocean State Crohn's and Colitis Area Registry cohort and the Mayo Clinic cohort. Baseline clinical risk factors were extracted according to the AGA pathway. Our primary end point was defined as follows: (i) any inflammatory bowel disease related-hospitalization, (ii) any inflammatory bowel disease-related bowel surgery, or (iii) any progression of disease. We analyzed the association of the number of AGA risk factors with our end point. Statistical multivariable modeling was performed with Cox proportional hazards model. RESULTS: A total of 412 patients with CD were included. Comparing ≥3 risk factors with 0-1 risk factor, we found a significantly increased risk of complications in both the Ocean State Crohn's and Colitis Area Registry cohort (hazard ratio [HR] 2.75, 95% confidence interval 1.71-4.41) and Mayo Clinic cohort (HR 2.07, 95% confidence interval 1.11-3.84). Diagnosis at younger age (HR 2.07), perianal disease (HR 1.99), and B2/B3 behavior (HR 1.92) were significantly associated with disease complications. We did not observe a consistent association between number of risk factors nor any specific individual risk factors and risk of disease complications in the 265 patients with UC included. DISCUSSION: We found a significant association between the number of AGA risk factors and the risk of disease complication in CD; this association was not significant in UC. The presence of ≥ 3 risk factors in CD leads to the highest risk of complications. The AGA care pathway is a useful tool to stratify patients who are at higher risk of disease complications in patients with CD.

Predictors of seizure outcomes of autoimmune encephalitis: A clinical and morphometric quantitative analysis study.

OBJECTIVE: Autoimmune encephalitis can be followed by treatment-resistant epilepsy. Understanding its predictors and mechanisms are crucial to future studies to improve autoimmune encephalitis outcomes. Our objective was to determine the clinical and imaging predictors of postencephalitic treatment-resistant epilepsy. METHODS: We performed a retrospective cohort study (2012-2017) of adults with autoimmune encephalitis, both antibody positive and seronegative but clinically definite or probable. We examined clinical and imaging (as defined by morphometric analysis) predictors of seizure freedom at long term follow-up. RESULTS: Of 37 subjects with adequate follow-up data (mean 4.3 yrs, SD 2.5), 21 (57 %) achieved seizure freedom after a mean time of 1 year (SD 2.3), and one third (13/37, 35 %) discontinued ASMs. Presence of mesial temporal hyperintensities on the initial MRI was the only independent predictor of ongoing seizures at last follow-up (OR 27.3, 95 %CI 2.48-299.5). Morphometric analysis of follow-up MRI scans (n = 20) did not reveal any statistically significant differences in hippocampal, opercular, and total brain volumes between patients with postencephalitic treatment-resistant epilepsy and those without. SIGNIFICANCE: Postencephalitic treatment-resistant epilepsy is a common complication of autoimmune encephalitis and is more likely to occur in those with mesial temporal hyperintensities on acute MRI. Volume loss in the hippocampal, opercular, and overall brain on follow-up MRI does not predict postencephalitic treatment-resistant epilepsy, so additional factors beyond structural changes may account for its development.

Efficacy of a two-dose hepatitis B vaccination with a novel immunostimulatory sequence adjuvant (Heplisav-B) on patients with chronic liver disease: a retrospective study.

Background: Patients with chronic liver disease (CLD) are more likely to have severe morbidity and mortality due to superimposed acute or chronic hepatitis B virus (HBV) infection and should receive routine vaccination against the virus. Heplisav-B is a two-dose, inactivated, yeast-derived vaccine that uses a novel immunostimulatory adjuvant. Our primary objective was to determine the efficacy of hepatitis B vaccination with Heplisav-B in patients with CLD. Methods: This retrospective cohort analysis included patients ≥18 years old with CLD who received Heplisav-B from January 2018 to January 2021. All patients had anti-HBs <10 IU/L prior to vaccination and received two doses of Heplisav-B. Post-vaccination anti-HBs of ≥10 IU/L was considered successful vaccination. Basic demographic information, laboratory markers, and medical history were collected from the electronic health record. Results: A total of 120 patients were included in analysis. The average age of patients was 59 years, 37% were female, and the most common etiology of liver disease was nonalcoholic fatty liver disease. Median days from 2nd vaccination to post-vaccination HBsAb levels was 121 days. 81/120 (67.5%) of patients had evidence of active immunity after receipt of Heplisav-B. On multivariable analysis, age >50 was associated with reduced odds of successful vaccination (OR =0.19, 95% CI: 0.03-0.76). Conclusions: In patients with CLD, Heplisav-B's overall efficacy (67.5%) is greater than reports of Engerix-B (33-45%), and thus is an effective hepatitis B vaccine in this patient population, particularly in cirrhotic patients. Further studies regarding this vaccine are needed in patients with CLD and after liver transplantation.

Efficacy of Hepatitis B Vaccination with a Novel Immunostimulatory Sequence Adjuvant (Heplisav-B) in Patients With Inflammatory Bowel Disease.

BACKGROUND: Owing to the use of immunosuppressive agents, patients with inflammatory bowel disease (IBD) have an increased risk of vaccine preventable diseases, including infection with hepatitis B virus (HBV). Heplisav-B, an FDA-approved vaccine, is more effective (90% to 100%) than Engerix-B (70.5% to 90.2%) at inducing immunity to HBV in clinical studies. Available data on efficacy of Heplisav-B vaccine in patients with IBD are limited. METHODS: This retrospective observational study included patients age 18 years and older with ulcerative colitis (UC) or Crohn's disease (CD) who received 1 or 2 doses of Heplisav-B vaccine and had postvaccination serologic testing. Prior to immunization, all participants were seronegative for HBsAb antibodies (HBsAb) measured as <10 IU/mL. Postvaccination HBsAb of ≥10 IU/mL was considered successful vaccination. Patient demographics, disease characteristics, and medications were abstracted. RESULTS: One hundred six patients were included in the analysis. Median age was 43 years, and 44 (42%) were female. Thirty-nine patients (37%) had UC, whereas 67 (63%) had CD. Eighty-three patients (78.3%) had active immunity after vaccination with Heplisav-B, with median postvaccination HBsAb levels of 114 IU/L. Patients with chronic obstructive pulmonary disease, chronic kidney disease, diabetes mellitus, immunomodulator use, or those on 2 or more of immunosuppressive medications were less likely to respond to Heplisav-B, though these findings were not statistically significant on a multivariate analysis aside from chronic kidney disease. CONCLUSIONS: Heplisav-B, a 2-dose vaccine, is an effective vaccine for HBV in patients with IBD. In our study, its overall efficacy (78.3%) is greater than that reported for the presently available 3-dose vaccination (Engerix) in patients with IBD.

Heplisav-B, a 2-dose vaccine, is an effective vaccine for HBV in patients with IBD. In our study, it had an overall efficacy of 78.3%. Patients on an immunomodulator and/or 2 or more immunosuppressants had decreased response rate to vaccination.

Higher Cell-Mediated Immune Responses in Patients With Inflammatory Bowel Disease on Anti-TNF Therapy After COVID-19 Vaccination.

BACKGROUND: Some patients with inflammatory bowel disease (IBD) on immunosuppressive therapies may have a blunted response to certain vaccines, including the messenger RNA (mRNA) coronavirus disease 2019 (COVID-19) vaccines. However, few studies have evaluated the cell-mediated immune response (CMIR), which is critical to host defense after COVID-19 infection. The aim of this study was to evaluate the humoral immune response and CMIR after mRNA COVID-19 vaccination in patients with IBD. METHODS: This prospective study (HERCULES [HumoRal and CellULar initial and Sustained immunogenicity in patients with IBD] study) evaluated humoral immune response and CMIR after completion of 2 doses of mRNA COVID-19 vaccines in 158 IBD patients and 20 healthy control (HC) subjects. The primary outcome was the CMIR to mRNA COVID-19 vaccines in patients with IBD. The secondary outcomes were a comparison of (1) the CMIR in patients with IBD and HC subjects, (2) CMIR and humoral immune response in all participants, and (3) correlation between CMIR and humoral immune response. RESULTS: The majority (89%) of patients with IBD developed a CMIR, which was not different vs HC subjects (94%) (P = .6667). There was no significant difference (P = .5488) in CMIR between immunocompetent (median 255 [interquartile range, 146-958] spike T cells per million peripheral blood mononuclear cells) and immunosuppressed patients (median 377 [interquartile range, 123-1440]). There was no correlation between humoral and cell-mediated immunity after vaccination (P = .5215). In univariable analysis, anti-tumor necrosis factor therapy was associated with a higher CMIRs (P = .02) and confirmed in a multivariable model (P = .02). No other variables were associated with CMIR. CONCLUSIONS: Most patients with IBD achieved CMIR to a COVID-19 vaccine. Future studies are needed evaluating sustained CMIR and clinical outcomes.

Antibody and T cell responses to coronavirus disease 2019 vaccines in patients with inflammatory bowel disease do not correlate. Most patients with inflammatory bowel disease mount a T cell response despite being on biologic therapies, those on anti-tumor necrosis factor may have a higher T cell response. Anti-tumor necrosis factor therapy has been associated with a lower antibody response to coronavirus disease 2019 vaccines, but the T cell response is augmented.

Improving detection of cerebral small vessel disease aetiology in patients with isolated lobar intracerebral haemorrhage.

BACKGROUND AND PURPOSE: We evaluate whether non-haemorrhagic imaging markers (NHIM) (white matter hyperintensity patterns, lacunes and enlarged perivascular spaces (EPVS)) can discriminate cerebral amyloid angiopathy (CAA) from hypertensive cerebral small vessel disease (HTN-cSVD) among patients with isolated lobar intracerebral haemorrhage (isolated-LICH). METHODS: In patients with isolated-LICH, four cSVD aetiologic groups were created by incorporating the presence/distribution of NHIM: HTN-cSVD pattern, CAA pattern, mixed NHIM and no NHIM. CAA pattern consisted of patients with any combination of severe centrum semiovale EPVS, lobar lacunes or multiple subcortical spots pattern. HTN-cSVD pattern consisted of any HTN-cSVD markers: severe basal ganglia PVS, deep lacunes or peribasal ganglia white matter hyperintensity pattern. Mixed NHIM consisted of at least one imaging marker from either pattern. Our hypothesis was that patients with HTN-cSVD pattern/mixed NHIM would have a higher frequency of left ventricular hypertrophy (LVH), which is associated with HTN-cSVD. RESULTS: In 261 patients with isolated-LICH, CAA pattern was diagnosed in 93 patients, HTN-cSVD pattern in 53 patients, mixed NHIM in 19 patients and no NHIM in 96 patients. The frequency of LVH was similar among those with HTN-cSVD pattern and mixed NHIM (50% vs 39%, p=0.418) but was more frequent in HTN-cSVD pattern compared with CAA pattern (50% vs 20%, p<0.001). In a regression model, HTN-cSVD pattern (OR: 7.38; 95% CI 2.84 to 19.20) and mixed NHIM (OR: 4.45; 95% CI 1.25 to 15.90) were found to be independently associated with LVH. CONCLUSION: Among patients with isolated-LICH, NHIM may help differentiate HTN-cSVD from CAA, using LVH as a marker for HTN-cSVD.

A Cohort Study of the Age at Menopause in Female Patients With and Without Inflammatory Bowel Disease.

Background: Menopause, defined by the complete cessation of menstrual cycles for 12 consecutive months, may occur at a younger age in women who have concomitant immune dysregulation. Our aim was to determine whether women with inflammatory bowel disease (IBD) experience an earlier onset of menopause compared to women without IBD. Methods: This was a retrospective cohort study using resources of the Rochester Epidemiology Project, a collaboration between clinics, hospitals, and medical facilities in Olmsted County, Minnesota. From these people, women who were diagnosed with IBD between 1970 and 2010 comprised the case cohort while the reference cohort included women with no diagnosis of IBD. Data including age, body mass index (BMI), ethnicity, smoking status, age at onset of menopause, and current use of hormone therapy were collected. Patients with history of hysterectomy or oophorectomy were excluded. Wilcoxon rank-sum test for numeric variables and Fisher's exact test for categorical variables were used to analyze the data. Results: A total of 171 women met criteria for inclusion (83 cases and 88 controls). Mean age of menopause in women with IBD was 50.0 years compared to 51.5 years in women with no IBD (P = .006). There was no difference in BMI of women with and without IBD (28.7 versus 28.2 kg m-2; P = .9), respectively. There were more former smokers (33.7%) and current (6%) smokers in the IBD group (P = .009) compared to the non-IBD group. Conclusions: IBD is associated with an earlier onset of menopause. Although it is unclear if this mean difference of 1.5 years is clinically relevant, it is known that early menopause is associated with an increased risk of osteoporosis and cardiovascular disease. Further research on the possible mechanisms is needed.

Endoscopic Management of Luminal Strictures: Beyond Dilation.

Luminal strictures can occur as part of many different gastrointestinal (GI) disorders anywhere along the GI tract and affect all age groups. The end goal of managing any stricture is to re-establish an adequate and durable luminal patency that is sufficient to resolve the presenting clinical symptoms. Treatment options can be generally categorized into medical, endoscopic, and surgical. However, within each of these categories, multiple different options are available. Therefore, choosing the best treatment modality is often challenging and depends on multiple factors including the type, location, and complexity of the stricture, as well as the preference of the treating physician. In this article, we will review the most current literature regarding foregut strictures, particularly esophageal and gastric, beyond dilation.

Faecal Calprotectin from Ileostomy Output Is Sensitive and Specific for the Prediction of Small Bowel Inflammation in Patients with Crohn's Disease.

BACKGROUND: Severe Crohn's disease [CD] can result in extensive bowel resections and need for creation of an ileostomy. Faecal calprotectin [FC] is well studied in CD management, though its role in patients who have an ileostomy is unclear. Our aim is to understand if FC is a useful adjunct to radiographic or endoscopic studies in identifying recurrent CD after surgery in patients with an ileostomy. METHODS: Between January 1, 2017, and September 30, 2020, we searched the Mayo Clinic electronic medical record retrospectively for adult patients with ICD-10 code for CD, and a surgical history of an ileostomy. Patients were included in the analysis if they had at least one FC measured and a concomitant radiographic imaging and/or endoscopic procedure. An abnormal FC was defined as greater than 60 µg/g. RESULTS: Of 51 patients who met our inclusion criteria, 17 had an FC level >60 µg/g. Of these 17 patients, 14 had imaging and/or an ileoscopy confirming the presence of small bowel inflammation, with a sensitivity of 87.5%. Of the remaining 34 patients with an FC level ≤60 µg/g, 32 patients had imaging and/or ileoscopy demonstrating no small bowel inflammation, with a specificity of 91.4%. FC from an ileostomy effluent had a positive predictive value of 82.3%, a negative predictive value of 94.1% and test diagnostic accuracy of 90.1%. CONCLUSION: FC from an ileostomy effluent is a highly sensitive and specific test for the assessment and monitoring of small bowel inflammation and disease recurrence in patients with CD.

Idiopathic primary intraventricular hemorrhage and cerebral small vessel disease.

BACKGROUND: Although primary intraventricular hemorrhage is frequently due to trauma or vascular lesions, the etiology of idiopathic primary intraventricular hemorrhage (IP-IVH) is not defined. AIMS: Herein, we test the hypothesis that cerebral small vessel diseases (cSVD) including hypertensive cSVD (HTN-cSVD) and cerebral amyloid angiopathy are associated with IP-IVH. METHODS: Brain magnetic resonance imaging from consecutive patients (January 2011 to September 2019) with non-traumatic intracerebral hemorrhage from a single referral center were reviewed for the presence of HTN-cSVD (defined by strictly deep or mixed-location intracerebral hemorrhage/cerebral microbleeds) and cerebral amyloid angiopathy (applying modified Boston criteria). RESULTS: Forty-six (4%) out of 1276 patients were identified as having IP-IVH. Among these, the mean age was 74.4 ± 12.2 years and 18 (39%) were females. Forty (87%) had hypertension, and the mean initial blood pressure was 169.2 ± 40.4/88.8 ± 22.2 mmHg. Of the 35 (76%) patients who received a brain magnetic resonance imaging, two (6%) fulfilled the modified Boston criteria for possible cerebral amyloid angiopathy and 10 (29%) for probable cerebral amyloid angiopathy. Probable cerebral amyloid angiopathy was found at a similar frequency when comparing IP-IVH patients to the remaining patients with primary intraparenchymal hemorrhage (P-IPH) (27%, p = 0.85). Furthermore, imaging evidence for HTN-cSVD was found in 8 (24%) patients with IP-IVH compared to 209 (28%, p = 0.52) patients with P-IPH. CONCLUSIONS: Among IP-IVH patients, cerebral amyloid angiopathy was found in approximately one-third of patients, whereas HTN-cSVD was detected in 23%-both similar rates to P-IPH patients. Our results suggest that both cSVD subtypes may be associated with IP-IVH.

Colchicine as an Alternative First-Line Treatment of Sclerosing Mesenteritis: A Retrospective Study.

BACKGROUND: Sclerosing mesenteritis is a rare condition characterized by chronic inflammation and fibrotic changes of the mesentery. AIMS: To determine the long-term management and outcomes of patients with sclerosing mesenteritis. METHODS: Patients with biopsy-proven sclerosing mesenteritis at the Mayo Clinic between January 2006 and December 2016 were identified. Clinical data were collected retrospectively. RESULTS: One hundred and three patients were identified, median age 68.0 years (range 35.0-85.3). Most patients were symptomatic (87.4%) at presentation. Patients received no treatment (52.4%), medical therapy (42.7%) or surgery (4.9%) on initial diagnosis. The most common initial regimens were prednisone plus tamoxifen (41.9%), prednisone alone (23.3%), and prednisone plus colchicine (11.6%) with 55.6%, 57.2%, and 60% of patients improving, respectively, p = 0.85 for a difference in response rates. At least half of the patients responded to prednisone plus tamoxifen, prednisone plus colchicine, or prednisone alone at 6.0, 7.2, and 8.4 months, respectively. At a median follow-up of 45.6 months (95% CI 24.1-69.7), 65.4% of patients were receiving medical therapy. Of those receiving tamoxifen-based, steroid-based, or steroid-sparing regimens, 100%, 87.5%, and 77.8% had improved by their last follow-up appointment respectively, p = 0.15. CONCLUSION: Prednisone plus colchicine has a similar efficacy to prednisone plus tamoxifen for the initial and long-term treatment of sclerosing mesenteritis. The majority of patients were initiated on medical therapy over the long term with most reporting symptomatic improvement within a year. Death from SM was rare.

Oral Contraceptive Pills Are an Effective Method of Preventing Pregnancy in Women With Crohn's Disease.

Background: Oral contraceptive pill (OCP) use in the general population is associated with a failure rate as low as 0.3% with perfect use but as high as 9% with typical use. Women with Crohn's disease (CD) may have malabsorption in the setting of small bowel disease or resection, which could affect absorption of OCPs. Our aim was to determine the incidence of pregnancy in women with CD on OCPs. Methods: This is a retrospective study assessing the incidence rate of OCP failure in females between 18 and 45 years of age seen at the Mayo Clinic with a diagnosis of CD and provided a prescription for OCPs, between 2016 and 2020. Failure was defined as clear documentation of becoming pregnant while using OCPs or having an active prescription of OCP at the time of conception. Results: A total of 818 female patients with CD between 18 and 45 years of age with a prescription for an OCP were included in our study. Sixty-six patients (8%) conceived in this cohort. Of the 66 patients who became pregnant, 57 stopped the OCP before conceiving, 5 were excluded due to lack of data, and 4 women had active oral contraceptive prescriptions when they became pregnant (pregnancy rate of 0.5%). Conclusions: In female patients with CD who are using OCPs for contraception, we found a low rate of pregnancy (0.5%) similar to the rate of pregnancy with perfect use of OCPs in the general population. OCPs are an effective method of birth control in women with CD.