Vitamin D and CRP are associated in hospitalized inflammatory bowel disease (IBD) patients in Shanghai.

Baseline Disease Activity and Steroid Therapy Stratify Risk of COVID-19 in Patients With Inflammatory Bowel Disease

SUMMARYInflammatory bowel diseases are multifactorial disorders the clinical manifestation of which depends on the interaction among immune response, genetic and environmental factors. There is growing evidence that cytokines and gene polymorphisms have an important role in disease pathogenesis in various populations although molecular mechanism of their signaling and interactions is not fully understood yet. The present study aimed at exploring the effects of interleukin-6, C-reactive protein and interleukin-6 rs1800795 polymorphism on the development of Crohn’s disease, ulcerative colitis and inflammatory bowel diseases overall and at determining differences between inflammatory bowel disease patients and healthy controls. A total of 132 inflammatory bowel disease patients and 71 healthy blood donors were investigated. In order to assess the clinical relevance of interleukin-6 and C-reactive protein serum concentration and interleukin-6 rs1800795 single nucleotide polymorphism in patients with Crohn’s disease and ulcerative colitis, we performed a cross-sectional, case-control study. Quantitative assessment of serum interleukin-6 and C-reactive protein was performed with solid-phase, enzyme-labeled, chemiluminescent sequential immunometric and immunoturbidimetric assay, respectively. A real-time fluorescence resonance energy transfer-based method on a LightCyclerTM PCR 1.2 was used for genotyping of IL-6 rs1800795 polymorphism. Both interleukin-6 and C-reactive protein serum levels were elevated in Crohn’s disease and ulcerative colitis patients. Positive correlations were observed between C-reactive protein and interleukin-6 serum concentration and ulcerative colitis activity index as measured by modified Truelove-Witt’s severity index scale. C-reactive protein serum level was higher in Crohn’s disease patients without intestinal resection than in Crohn’s disease patients with prior intestinal resection. In ulcerative colitis patients, interleukin-6 and C-reactive protein serum levels were statistically significantly higher in CC interleukin-6 genotype in comparison to GG+GC genotype. Analysis of the promoter region of the interleukin-6 rs1800795 gene polymorphism showed no statistically significant difference in allele frequency either between inflammatory bowel disease patients and healthy controls or between the two inflammatory bowel disease phenotypes and healthy controls. Associations presented in this study give a potentially important insight into the role of interleukin-6 and C-reactive protein signaling and interleukin-6 polymorphism in the pathogenesis of Crohn’s disease and ulcerative colitis disease.

Therapeutic Drug Monitoring of Tumor Necrosis Factor Antagonists in Inflammatory Bowel Disease

Introduction: Several biologics now exist as treatment for inflammatory bowel disease (IBD) but effective induction of remission still ranges between 20-40% for most. Studies suggest that diet may modify intestinal inflammation. In this study, we sought to examine the effect of diet on biochemical response to biologic induction therapies. Methods: We conducted a single-center retrospective analysis of patients with IBD seen at a tertiary referral center from 2019 to 2021. A validated 26-item diet questionnaire, the Dietary Screener Questionnaire (DSQ), was completed as part of a pre-check-in process before each clinic visit. IBD patients who completed a DSQ within three months of induction of a biologic (anti-TNFs, vedolizumab, ustekinumab) and who had markers of inflammation available pre and post-induction (C-Reactive Protein (CRP)) were included. Follow up period was 3 months post-induction. Using linear and average mixed-effects models, we examined the contribution of food items in the DSQ (i.e., processed meats, red meats, fruits, vegeTables) to a reduction in CRP following induction. We used pre-induction biochemical markers as a baseline reference. Current steroid use, prior biologic exposure, age, gender, body mass index (BMI), smoking status, IBD type (ulcerative colitis (UC) or Crohn’s disease (CD)), and class of biologic were added as covariates in the models. Results: A total of 105 patients were included in this study (62.9% had CD and 32.4% had UC). The most common biologic was anti-TNFs (52.4%). The mean CRP value pre-induction was 13.4 (SD 20.2) and post-induction was 6.63 (SD 12.4). On multivariable analyses adjusting for covariates mentioned, we found an independent effect of high daily intake of fruits and vegeTables on reduction in CRP. For every 1 unit increase in daily fruits and vegeTables, there was a reduction in CRP value by 1.82 post-induction of biologics (p=0.04), Table. Red meat intake, processed meats, fiber from whole grains, and dairy were not associated with CRP reduction (Table). Conclusion: In this preliminary analysis, we find that a diet high in fruits and vegeTables during induction of biologics may independently improve biochemical response. Future clinical drug trials should consider dietary assessment and the influence of diet on response to medication treatment. Table 1. - Average Marginal Effects (AME) Assessing the Contribution of Each Variable on the Reduction of CRP Level During Induction Factor Average Mixed Effects (AME) Standard Error (SE) p-value Age 0.1253 0.07186 0.862 Gender (Male) 0.30313 0.23377 0.1977 BMI 0.08005 0.07203 0.2701 IBD- Ulcerative Colitis -0.33136 0.14984 0.0304 Previous biologic use -0.03417 0.14799 0.818 anti-TNF biologic induced (ref) 1.29018 0.94172 0.1734 Ustekinumab induced 0.10442 0.15699 0.5082 Vedolizumab induced 0.1059 0.17734 0.5525 Steroids on induction 0.23593 0.14915 0.1181 Diet Factors Red Meat -0.01567 0.17881 0.9303 Processed Meat -0.32794 0.34438 0.343 Fiber 0.5546 0.05404 0.3071 Calcium 0.15903 0.19979 0.4277 Whole grain (cups) -0.40034 0.26105 0.1279 Added sugar (teaspoons) -0.01585 0.0235 0.5014 Dairy (cups) 0.0488 0.32823 0.8821 Fruit (cups) 0.62825 0.76457 0.413 Fruits and Vegetables daily (cups) -1.8186 0.87858 0.0406

INTRODUCTION: Currently, the disease course and clinical outcomes of obese patients with inflammatory bowel disease (IBD) have been mixed. This study aims to compare biomarkers of inflammation such as erythrocyte sedimentation rate (ESR) and c-reactive protein (CRP) in both obese and non-obese African American (AA) and Caucasian populations. METHODS: We conducted a prospective observational study of consecutive Crohn's disease (CD) and ulcerative colitis (UC) patients in the outpatient setting at a tertiary referral center between 2014-2017. Body mass index (BMI), ESR, CRP, hemoglobin (Hgb) were measured at 2 consecutive visits. Obesity was defined as a BMI ≥30. The Wilcox signed rank test was used to compare continuous variables, and the Chi square test for categorical variables. A multivariate logistic regression model was created to look at change in CRP (no change, increase by half, decrease by half) from initial to follow-up visit. The regression model analysis included ethnicity, gender, BMI, type of IBD (CD versus UC), age, alcohol use, tobacco use, hypertension, kidney disease, heart disease, and treatment as covariates. RESULTS: The study included 92 subjects, 65% had CD and 30% were AA (Table 1). The average time between visits was 136 days. In the obese group, 33% were AA and 70% were female. Also, a larger portion of CD patients were obese compared to UC patients (37% and 11% respectively with P = 0.03). There was a significant decrease in the CRP in the obese group (P = 0.029) whereas non-obese individuals had an increase in CRP (Table 2). There was no significant difference in ESR and hemoglobin (Hgb) between obese and non-obese individuals. 63 patients where included in the regression model, which showed that a decrease in CRP was significantly associated with obesity (P = 0.0081) when adjusted for the above covariates. Overall, obese individuals were more likely to experience no change in CRP or a decrease in CRP while non-obese individuals were more likely to have a rise in CRP. There was no difference in clinical disease activity indices (HBI/SCCAI) between obese and non-obese patients. CONCLUSION: In our study, the obese patients were more likely to be female, have CD, and be Caucasian. While there was no difference in Hgb or ESR in obese versus non-obese, there is a difference in CRP. CRP could have importance as a sensitive marker for disease course in patients whose BMI ≥30. A larger cohort may provide further insight into this observation.

Increased C-reactive protein (CRP) levels are associated with coronary heart disease, stroke, and mortality. Physical activity prevents cardiovascular disorders, which can be partly mediated through reducing inflammation, including serum CRP levels. The association of different intensities of physical activity, sedentary behaviours, and C-reactive protein (CRP) levels in serum was examined after adjustment for markers of adiposity, including waist-circumference and body mass index (BMI), in a large population-based study. Using data of the SuRFNCD-2007 study, a large national representative population-based study in Iran, the relationship between quantitative CRP concentrations in serum and physical activity was examined in a sample of 3,001 Iranian adults. The global physical activity questionnaire (GPAQ) was used for evaluating the duration and intensity of physical activity. Total physical activity (TPA) was calculated using metabolic equivalents for the intensity of physical activity. Quantitative CRP concentrations in serum were measured with high-sensitivity enzyme immunoassay. The CRP levels in serum significantly correlated with TPA (r=-0.103, p=0.021 in men and r=-0.114, p=0.017 in women), duration of vigorous-intensity activity (r=-0.122, p=0.019 in men and r=-0.109, p=0.026 in women), duration of moderate-intensity activity (r=-0.107, p=0.031 in men and r=-0.118, p=0.020 in women), and duration of sedentary behaviours (r=0.092, p=0.029 in men and r=0.101, p=0.022 in women) after multiple adjustments for age, area of residence, BMI, waist-circumference, smoking, and diabetes mellitus. Physical activity (of both moderate and vigorous intensity) is inversely associated with the quantitative CRP levels in serum, independent of diabetes and body adiposity.

Background Vitamin D exerts an important role in the immune regulation. Several studies from the Western countries showed low level of vitamin D among inflammatory bowel disease (IBD) patients. They also showed that vitamin D may have an influence on disease activity. Data from the Eastern Europe are scarce. The aim of this study was to evaluate vitamin D level and the association between vitamin D and disease activity in biologic naïve patients with IBD. Methods This is a prospective study carried out at a tertiary hospital center in Albania from 2016–2020 including consecutive biologics–naïve IBD patients. Demographic and clinical data [age, gender, body mass index (BMI), disease location, extent, activity and duration) were collected. All patients underwent ileocolonoscopy. Vitamin D level and C-reactive protein (CRP) were measured within 2 weeks of their ileocolonoscopy. Montreal classification was used to evaluate the disease extent, while total Mayo score and Crohn’s disease activity index (CDAI) were used to assess disease activity in patients with ulcerative colitis (UC) and Crohn’s disease (CD) respectively. Vitamin D levels were considered as: normal >30ng/ml; insufficient 10–30 ng/ml; deficient <10ng/ml. Results A total of 96 patients were included in this study; mean age was 43.5±15.8 years, 52% females; 85.4% UC, mean disease duration 6.5±5 years. Vitamin D levels ranged from 3–58 ng/mL, with a mean level of 18 ±9.9 ng/ml (CD:17.5±12.4 ng/mL, UC:18.1±9.5, p=0.826). 63/96 patients (66%) had vitamin D deficiency (73.2% UC and 21.4% CD, p<0.001), while 21/96 (22%) had vitamin D insufficiency. There was no significant difference in vitamin D insufficiency and IBD type (p>0.05), although the insufficiency was found higher among CD that UC patients [7/14 (50%) vs 14/82 (17%) respectively]. No statistically significant association was found between vitamin D level and age, gender, BMI, disease type, activity, location, extent and duration. There was a negative correlation between CRP and vitamin D level (r=−0.178, p=0.054). Conclusion Low vitamin D levels are common in biologic-naïve patients with IBD. These levels are not associated with clinical data such as disease type, extent, duration or severity in IBD patients, but it seems that vitamin D influences the presence of inflammation in these patients.

Anti-Saccharomyces cerevisiae IgG and IgA antibodies are associated with systemic inflammation and advanced disease in hidradenitis suppurativa

INTRODUCTION: Inflammatory Bowel Disease (IBD) is associated with changes in body composition of patients. Recent studies have shown that the prevalence of obesity is rising in patients with IBD, where 15-40% of adults are obese and 20-40% are considered overweight. One prospective study analyzed body composition in IBD patients overtime and noted that despite an overall increase in adiposity, the total muscle mass was decreased. Low lean muscle mass has an association with poor response to therapy, surgical outcomes and the quality of life in IBD patients. Low C-reactive protein (CRP) levels after initiation of anti-TNF therapy have been associated with mucosal healing on surveillance colonoscopies and clinical disease remission. The aim of this study is to analyze the association between BMI and CRP with progression of IBD, using anti- TNF use as a surrogate marker for disease severity. METHODS: Medical records at Kings County Medical Center in Brooklyn, New York were queried for patients with the ICD 9 and 10 code diagnoses for Crohn's disease (CD) and Ulcerative Colitis (UC) from 2015 to 2018. Biographical, laboratory and endoscopic data, including BMI and CRP, was collected and analyzed. RESULTS: 148 patients with IBD were analyzed from 2015-2018; where 57.2% had UC and 42.8% had CD. Mean age of patients was 47.4 years, and 53.4% of patients were females. The average BMI prior to initiation of therapy was 27.6 kg/m2. The average years diagnosed with IBD was 11.1 years. Of the total patients, 37 were on biologic therapy. In the BMI group, the odds ratio was 0.905 indicating that patients with a lower BMI had more severe disease. The P value was 0.068, not significant but trended towards significance. In the CRP group, the odds Ratio was 1.020, which signified that patients with higher CRP values had more severe disease, with a P value of 0.046. CONCLUSION: The results of our small retrospective study suggest that a lower BMI and higher CRP are independent predictors of severe disease. Our study demonstrated that severe IBD, as measured by anti-TNF use, is associated with high CRP levels. We believe that low BMI and high CRP measurements may be used in conjunction with endoscopic findings and clinical presentation to escalate therapy early preventing worsening of disease. Further studies can be done to also incorporate endoscopic scoring system on surveillance colonoscopies to confirm the correlation between lower BMI and higher CRP with severity of disease.

Inflammatory Bowel Disease Clinical

Background. Inflammatory bowel disease (IBD) is a group of idiopathic, chronic, relapsing inflammatory conditions of the gastrointestinal tract including ulcerative colitis (UC), Crohn's disease (CD), and unspecified colitis (UnC). Objective. To provide a comparative characteristic of clinical and laboratory features of various IBD types in children according to the morphology, and to identify clinical and laboratory markers of unspecified colitis in children. Material and methods. 118 pediatric patients diagnosed with chronic inflammatory bowel disease were observed. Statistical processing of clinical and laboratory data was carried out using the statistical package R, version 4.1. Results. A comprehensive examination revealed 36 patients with Crohn's disease (CD), 54 those with ulcerative colitis (UC), and 28 with UnC. It was found out that in patients diagnosed with unspecified colitis, clinical manifestations were statistically more often observed at an earlier age (28,5 months [8; 50]) in contrast to children with UC (31 months [14; 122]) and CD patients (96 months [34,5;132]) (p=0,004). All patients with IBD had significant changes in stool frequency (from 3 to 9 or more times per day), 45 (83.3%) patients with UC having blood in stool (p <0.001). Pain syndrome was less common in patients diagnosed with UnC – 22 (78,6%) (p=0,048). The two clinical and laboratory symptoms were significantly more often observed in the group of patients with UC: protein-energy malnutrition (PEM) – 24 (44,4%)(p=0.008) and anemia – 39 (72,2%) (p<0.001). Patients diagnosed with UnC had a lower platelet count (292±68) (p=0.005). CD patients had a lower mean relative lymphocyte count (30,8%) (p=0.005). The level of C-reactive protein (CRP) was significantly more often elevated in patients with UC – 30 (55,6%) (p=0,005). Conclusions. Though standard methods used for examining patients with IBD allow us to establish the diagnoses of UC and CD, such examination is not sufficient for children with UnC. It is necessary to include new molecular genetic criteria in the examination protocol for patients with IBD, which will make it possible to offer appropriate treatment at an early stage of the disease.

Background: Increasing evidences suggest that hypovitaminosis D can play an important role in immuno-mediated diseases, such as Inflammatory Bowel Diseases (IBD). The hypovitaminosis D is an established risk factor for the development of osteopenia, osteoporosis and pathological fractures. Studies have reported a correlation between hypovitaminosis D, disease history and clinical features in Crohn's Disease (CD) and Ulcerative Colitis (UC). The aim of this study is to evaluate the vitamin D serum levels and the prevalence of bone mineral density (BMD) alterations in a population of Italian IBD patients and to correlate the prevalence of hypovitaminosis D with disease history and clinical features. Method: Between October 2013 and November 2014 we enrolled patients from our center that were affected by UC or CD. Exclusion criteria were age below 18 and over 60, concomitant vitamin D replacement therapy and concomitant gastrointestinal or endocrinological diseases which may alter vitamin D metabolism. All patients underwent 25-OH-vitamin D, ESR, C-reactive protein (CRP), PTH, serum calcium and phosphorus, β-CTX, alkaline phosphatase (bone isoenzyme) plasma assay and bone mass density (BMD) evaluation by lumbar and femoral dual-energy X-ray absorptiometry (DXA) scan. Both measurements were made at the same time, during the autumn and winter months. Following 2012 Osteoporosis Italian Society Guidelines, we defined as hypovitaminosis D plasmatic values <30 ng/mL, vitamin D levels were considered as insufficient if between 20 and 30 ng/ mL and deficient if <20 ng/mL. We collected data regarding patients’ life habits and clinical history, disease course and disease clinical activity at enrollment. For BMD evaluation T-score and/or Z-score were calculated for each patient at lumbar (L1-L4) and femoral neck level, and the diagnosis of osteopenia or osteoporosis was made according to international guidelines. Results: We enrolled 88 patients (62 CD, 26 UC); median age at enrollment was 42 years for CD and 43 years for UC. Mean Body Mass Index (BMI) was 22.6 in CD and 23.7 in UC patients. Age at diagnosis was 29.8 years for CD and 33.5 years for UC, with mean disease duration of 12.8 years for CD and 9.1 years for UC.Hypovitaminosis D was observed in 84.1% of the patients. Of these, 31.8% had insufficient vitamin D levels, whereas 57.3% deficient. Mean vitamin D level was 20.4 ng/mL, but there was no difference with respect to sex or disease type. Indeed, there was no correlation between hypovitaminosis D and disease duration or patients age at diagnosis. A statistically significant correlation was found between hypovitaminosis D and history of steroid-dependancy (p=0.03), need of therapy with anti- TNF-α drugs (p=0.01) and cigarette smoke habit in CD patients (p=0.01). In CD patients we also found a correlation, at the limit of statistical significance (p=0.05), between hypovitaminosis D, high CRP values and HarveyBradshaw Index (HBI) at enrollment.70 patients underwent the lumbar DXA analysis, 67 the femoral DXA. Lumbar BMD was found to be below the normal range in 37.1% of the patients, suggesting that 24.2% and 12.9% were affected by osteopenia or osteoporosis, irrespective of sex and disease type (CD or UC). Similarly, femoral BMD was below the normal range for age in 43.3% of the patients. This figure is consistent with osteopenia or osteoporosis in 34.3% and 9%, irrespective of sex and disease type and femoral Z-score that was found significantly lower in CD than UC patients (p=0.03). Reduced BMD correlated with lower BMI and hypovitaminosis D. Conclusion: In our study we found a high prevalence of hypovitaminosis D in an IBD population irrespective of patients' sex, type and duration of disease. Our data show a strong correlation between hypovitaminosis D and a more aggressive disease course in terms of history of steroiddependancy, need of therapy with anti TNF-α drugs and smoke habit in CD patients. Hypovitaminosis D may play a crucial role in causing a more severe clinical behavior of IBD. Alteration of bone metabolism is a concern in IBD patients. We observed a high prevalence of BMD alterations in both men and women affected by UC and CD, even if of young age and with a short disease duration, irrespective of the type of IBD. Such patients may be prescribed lumbar and femoral, especially in cases of hypovitaminosis D and low BMI. This would allow an early diagnosis of BMD alterations, to start specific therapy and to prevent further complications.

BACKGROUND: Medical practices have increased electronic messaging and telemedicine visits during the last several years. This rise in electronic health care during the COVID pandemic minimized SARS-CoV-2 exposure and disease transmission. Historically, African-Americans and older patients have less frequently used electronic messaging with their physicians. This study compares the utilization of virtual health care before and during the COVID pandemic by inflammatory bowel disease (IBD) patients. METHODS: A retrospective medical record review of all IBD patients seen at an academic medical center from 2014 to 2020 was conducted to evaluate the use of telehealth options (e-messaging, e-visits) during a pre-COVID and a COVID timeframe. Patient age, gender, race, IBD subtype (Crohn's disease, ulcerative colitis or indeterminate colitis), electronic messaging, and telehealth visits were obtained. A pre-COVID IBD cohort was identified from the 2015–2018 records. The pre-COVID timeframe evaluated was March-August 2018. A COVID IBD cohort was identified from the 2017–2020 records. The COVID timeframe evaluated was March-August 2020. A confidential database was created using Microsoft Excel. Statistical analysis was performed using Fisher Exact test with significance set at P < 0.05. The study was IRB approved. RESULTS: There were 392 patients (174 males, 218 females; mean age 44.4 years) in the pre-COVID cohort. 97 had Crohn's disease, 278 had ulcerative colitis and 17 had indeterminate colitis. There were 204 White, 99 African American, 11 Asian, and 78 ethnically un-identified patients. One hundred sixty (40.8%) initiated E-communication with their physicians, however E-visits were not an option. E-messaging was initiated significantly more by White patients compared to African American patients (62.3% vs 28.2%; P < 0.00001). Patients <50 years of age used e-messaging significantly more than those > 50 (51.1% vs 39.7%; P = 0.0396). There were no significant differences in the use of e-messaging based upon patient gender (P = 0.6840) or IBD type (P = 0.6374). There were 295 patients (130 males, 165 females; mean age 45.7 years) in the COVID cohort. 76 had Crohn's disease and 208 had ulcerative colitis. There were 155 White, 83 African American patients, 24 Hispanic patients, 10 Asian patients, and 22 ethnically un-identified patients. 109 (36.9%) utilized a telehealth option (53 via e-messaging; 56 via telemedicine visit). There was no significant difference in the use of a telehealth option based upon race (42.6% White vs 35.9% African-American; P = 0.2693), age (36.8% < 50 vs 37.25% > 50 years; P = 1.00) or IBD type (P = 0.331). Males used telehealth more than females (46.1% vs 29.7%, respectively; P = 0.0051). CONCLUSION: The COVID pandemic encouraged physicians to incorporate telehealth options into their practice. Prior to the COVID pandemic, patients were able to e-message their physicians. However, the pandemic emergency enabled medical practices to offer e-visits in addition to e-messaging for care delivery. This study revealed that expanded telemedicine options for IBD patients eliminated previously identified racial and age disparities in virtual medical care. Further study is needed to understand gender differences in telehealth utilization. There should be post-pandemic policy consideration for continued telemedicine options to encourage expanded patient-physician engagement, support continuity in care and optimize IBD outcomes.

This Month in Gastroenterology

COVID-19 Vaccination Is Safe and Effective in Patients With Inflammatory Bowel Disease: Analysis of a Large Multi-institutional Research Network in the United States