Increasing thirty-day readmissions of Crohn’s disease and ulcerative colitis in the United States: A national dilemma

BACKGROUNDThe prevalence of Crohn’s disease (CD) and ulcerative colitis (UC) is on the rise worldwide. This rising prevalence is concerning as patients with CD and UC may frequently relapse leading to recurrent hospitalizations and increased healthcare utilization.AIMTo identify trends and adverse outcomes for 30 d readmissions for CD and UC. METHODSThis was a retrospective, interrupted trends study involving all adult (≥ 18 years) 30 d readmissions of CD and UC from the National Readmission Database (NRD) between 2008 and 2018. Patients < 18 years, elective, and traumatic hospitalizations were excluded from this study. We identified hospitalization characteristics and readmission rates for each calendar year. Trends of inpatient mortality, mean length of hospital stay (LOS) and mean total hospital cost (THC) were calculated using a multivariate logistic trend analysis adjusting for age, gender, insurance status, comorbidity burden and hospital factors. Furthermore, trends between CD and UC readmissions were compared using regression of the interaction coefficient after adjusting for age and gender to determine relative trends between the two populations. Stata^® Version 16 software (StataCorp, TX, United States) was used for statistical analysis and P value ≤ 0.05 were considered statistically significant. RESULTSTotal number of 30 d readmissions increased from 6202 in 2010 to 7672 in 2018 for CD and from 3272 in 2010 to 4234 in 2018 for UC. We noted increasing trends for 30-day all-cause readmission rate of CD from 14.9% in 2010 to 17.6% in 2018 (P-trend < 0.001), CD specific readmission rate from 7.1% in 2010 to 8.2% in 2018 (P-trend < 0.001), 30-day all-cause readmission rate of UC from 14.1% in 2010 to 15.7% in 2018 (P-trend = 0.003), and UC specific readmission rate from 5.2% in 2010 to 5.6% in 2018 (P-trend = 0.029). There was no change in the risk adjusted trends of inpatient mortality and mean LOS for CD and UC readmissions. However, we found an increasing trend of mean THC for UC readmissions. After comparison, there was no statistical difference in the trends for 30 d all-cause readmission rate, inpatient mortality, and mean LOS between CD and UC readmissions.CONCLUSIONThere was an increase in total number of 30 d readmissions for CD and UC with a trend towards increasing 30 d all-cause readmission rates.     

An assessment of serum vitamin B12 and folate in patients with Crohn’s disease

Crohn’s disease is a chronic inflammatory condition that can involve any area in the gastrointestinal tract often involving the distal ileum where vitamin B12 is specifically absorbed. The aim of this study was to ascertain serum vitamin B12 and folate levels in order to investigate the correlation among these vitamin levels and disease activation, localization, duration and age at the onset of the disease.Study population included 103 patients with Crohn’s disease and a healthy control group of 114 individuals. C-reactive protein, vitamin B12, folate levels were studied along with hemogram analyses. The results were evaluated in statistical comparisons. While serum vitamin B12 levels and serum folate levels were 161.9 ± 63.2(73–496) pg/mL and 4.9 ± 1.4(1.2–9.4) ng/mL in the Crohn’s patient group respectively, they were 321.7 ± 126.3(85–680) pg/mL and 7.6 ± 3.8(3–25.1) ng/mL in the control group respectively. Vitamin B12 and folate levels were distinctly lower in patients with Chron’s disease than those of the control group (P < .001). The intragroup analysis of the patient group revealed that low vitamin B12 levels were significantly lower in the moderate group classified according to the Crohn’s Disease Activity Index (P < .001), along with those in the L1 group with terminal/distal ileal involvement (P < .001).Vitamin B12 and folate deficiencies are quite prevalent in patients with Crohn’s disease while this condition can lead to various complications and they prove to be important risk factors associated especially with thrombosis and its complications. Patients must be regularly followed-up for vitamin B12 and folate levels to supplement them where needed.     

Evaluation of inflammatory activity in Crohn's disease and ulcerative colitis

Crohn's disease and ulcerative colitis evolve with a relapsing and remitting course. Determination of inflammatory state is crucial for the assessment of disease activity and for tailoring therapy. However, no simple diagnostic test for monitoring intestinal inflammation is available. Noninvasive markers give only indirect assessments of disease activity. Histopathological or endoscopical examinations accurately assess inflammatory activity, but they are invasive, time consuming and expensive and therefore are unsuitable for routine use. Imaging procedures are not applicable for ulcerative colitis. The usefulness of ultrasound and Doppler imaging in assessing disease activity is still a matter of discussion for Crohn's disease, and an increased interest in computed tomography enterograph (CTE) has been seen, mainly because it can delineate the extent and severity of bowel wall inflammation, besides detecting extraluminal findings. Until now, the available data concerning the accuracy of magnetic resonance enterography in detecting disease activity is less than CTE. Due to this, clinical activity indices are still commonly used for both diseases.     

Outcomes of Pediatric Fistulising Perianal Crohn’s Disease

Background: Perianal disease is reported more widely in pediatric Crohn patients than in the past, and has been stated as an independent modifier of the disease behavior. In this study, we aimed to analyze the clinical characteristics and outcomes of fistulising perianal Crohn’s disease (fpCD) in the pediatric age group.Methods: A total number of 149 children with an established diagnosis of inflammatory bowel disease who have been diagnosed before 18 years of age and followed in our tertiary center were revised. Clinical, endoscopic, laboratory, and radiologic data of 50 patients with CD, who had at least 18 months follow-up data, were compiled.Results: Of 50 patients, 26 (52%) were diagnosed as fpCD (38% at onset). More than half of the patients without any notable external orifices around the perianal area were diagnosed as fpCD by an magnetic resonance imaging (MRI). Pediatric fpCD patients had a higher disease activity score and platelet count, lower serum albumin level, and a higher rate of granuloma in the biopsy samples, compared with non-fistulising patients. A considerably high rate of surgical interventions (i.e., seton placement 46% and abscess drainage 15%) was performed in combination with infliximab.Conclusion: Fistulising perianal Crohn’s disease seems to be more common than previously reported in the pediatric age group. A severe course of the disease might serve as a warning for the development of fpCD. A careful physical examination and use of perianal MRI with a high index of suspicion may increase the likelihood of fistula detection, hence may change the treatment strategy.     

Establishing a rabbit model of perianal fistulizing Crohn’s disease

BACKGROUNDCrohn''s disease (CD) is a chronic nonspecific intestinal inflammatory disease. The aetiology and pathogenesis of CD are still unclear. Anal fistula is the main complication of CD and is a difficult problem to solve at present. The main limitation of developing new therapies is bound up with the short of preclinical security and effectiveness data. Therefore, an ideal animal model is needed to establish persistent anal fistula and an inflamed rectal mucosa.AIMTo improve the induction method of colitis and establish a reliable and reproducible perianal fistulizing Crohn’s disease animal model to evaluate new treatment strategies.METHODSTwenty male New Zealand rabbits underwent rectal enema with different doses of 2,4,6-trinitrobenzene sulfonic acid to induce proctitis. Group A was treated with an improved equal interval small dose increasing method. The dosage of group B was constant. Seven days later, the rabbits underwent surgical creation of a transsphincteric fistula. Then, three rabbits were randomly selected from each group every 7 d to remove the seton from the fistula. The rabbits were examined by endoscopy every 7 days, and biopsy forceps were used to obtain tissue samples from the obvious colon lesions for histological analysis. The disease activity index (DAI), colonoscopy and histological scores were recorded. Perianal endoscopic ultrasonography (EUS) was used to evaluate the healing of fistulas.RESULTSExcept for the DAI score, the colonoscopy and histological scores in group A were significantly higher than those in group B (P < 0.05). In the ideal model rabbit group, on the 7^th day after the removal of the seton, all animals had persistent lumens on EUS imaging, showing continuous full-thickness high signals. Histological inspection of the fistula showed acute and chronic inflammation, fibrosis, epithelialization and peripheral proctitis of the adjoining rectum.CONCLUSIONThe improved method of CD colitis induction successfully established a rabbit perianal fistula CD preclinical model, which was confirmed by endoscopy and pathology.     

Crohn’s and colitis in children and adolescents

Crohn’s disease and ulcerative colitis can be grouped as the inflammatory bowel diseases (IBD). These conditions have become increasingly common in recent years, including in children and young people. Although much is known about aspects of the pathogenesis of these diseases, the precise aetiology is not yet understood, and there remains no cure. Recent data has illustrated the importance of a number of genes-several of these are important in the onset of IBD in early life, including in infancy. Pain, diarrhoea and weight loss are typical symptoms of paediatric Crohn’s disease whereas bloody diarrhoea is more typical of colitis in children. However, atypical symptoms may occur in both conditions: these include isolated impairment of linear growth or presentation with extra-intestinal manifestations such as erythema nodosum. Growth and nutrition are commonly compromised at diagnosis in both Crohn’s disease and colitis. Consideration of possible IBD and completion of appropriate investigations are essential to ensure prompt diagnosis, thereby avoiding the consequences of diagnostic delay. Patterns of disease including location and progression of IBD in childhood differ substantially from adult-onset disease. Various treatment options are available for children and adolescents with IBD. Exclusive enteral nutrition plays a central role in the induction of remission of active Crohn’s disease. Medical and surgical therapies need to considered within the context of a growing and developing child. The overall management of these chronic conditions in children should include multi-disciplinary expertise, with focus upon maintaining control of gut inflammation, optimising nutrition, growth and quality of life, whilst preventing disease or treatment-related complications.     

Inflammatory bowel disease in India - Past,present and future

There is rising incidence and prevalence of inflammatory bowel disease (IBD) in India topping the Southeast Asian (SEA) countries. The common genes implicated in disease pathogenesis in the West are not causal in Indian patients and the role of “hygiene hypothesis” is unclear. There appears to be a North-South divide with more ulcerative colitis (UC) in north and Crohn’s disease (CD) in south India. IBD in second generation Indian migrants to the West takes the early onset and more severe form of the West whereas it retains the nature of its country of origin in migrants to SEA countries. The clinical presentation is much like other SEA countries (similar age and sex profile, low positive family history and effect of smoking, roughly similar disease location, use of aminosalicylates for CD, low use of biologics and similar surgical rates) with some differences (higher incidence of inflammatory CD, lower perianal disease, higher use of aminosalicylates and azathioprine and lower current use of corticosteroids). UC presents more with extensive disease not paralleled in severity clinically or histologically, follows benign course with easy medical control and low incidence of fulminant disease, cancer, complications, and surgery. UC related colorectal cancer develop in an unpredictable manner with respect to disease duration and site questioning the validity of strict screening protocol. About a third of CD patients get antituberculosis drugs and a significant number presents with small intestinal bleed which is predominantly afflicted by aggressive inflammation. Biomarkers have inadequate diagnostic sensitivity and specificity for both. Pediatric IBD tends to be more severe than adult. Population based studies are needed to address the lacunae in epidemiology and definition of etiological factors. Newer biomarkers and advanced diagnostic techniques (in the field of gastrointestinal endoscopy, molecular pathology and genetics) needs to be developed for proper disease definition and treatment.     

Palmitoylation in Crohn’s disease: Current status and future directions

S-palmitoylation is one of the most common post-translational modifications in nature; however, its importance has been overlooked for decades. Crohn’s disease (CD), a subtype of inflammatory bowel disease (IBD), is an autoimmune disease characterized by chronic inflammation involving the entire gastrointestinal tract. Bowel damage and subsequent disabilities caused by CD are a growing global health issue. Well-acknowledged risk factors for CD include genetic susceptibility, environmental factors, such as a westernized lifestyle, and altered gut microbiota. However, the pathophysiological mechanisms of this disorder are not yet comprehensively understood. With the rapidly increasing global prevalence of CD and the evident role of S-palmitoylation in CD, as recently reported, there is a need to investigate the relationship between CD and S-palmitoylation. In this review, we summarize the concept, detection, and function of S-palmitoylation as well as its potential effects on CD, and provide novel insights into the pathogenesis and treatment of CD.     

Glucagon-like peptide-2 analogues for Crohn’s disease patients with short bowel syndrome and intestinal failure

Short bowel syndrome (SBS) with intestinal failure (IF) is a rare but severe complication of Crohn’s disease (CD), which is the most frequent benign condition that leads to SBS after repeated surgical resections, even in the era of biologics and small molecules. Glucagon-like peptide-2 analogues have been deeply studied recently for the treatment of SBS-IF. These drugs have a significant intestinotrophic effect and the potential to reduce the chronic dependence of SBS-IF patients on parenteral support or nutrition. Teduglutide has been approved for the treatment of SBS-IF, and apraglutide is currently in clinical development. The use of these drugs was examined with a focus on their use in CD patients.     

Turkish IBD Organization’s Position Statement on Inflammatory Bowel Disease Management Recommendations During COVID-19 Pandemic

The COVID-19 pandemic, caused by the novel severe acute respiratory syndrome coronavirus 2, has resulted in high mortality and morbidity worldwide and is still a growing problem. Inflammatory bowel disease (IBD) is a chronic inflammatory disease for which a substantial number of patients are treated with immunosuppressive medications, either occasionally or long-term. Despite the accumulating evidence, there is still a lack of knowledge about the impact of COVID-19 on IBD patients, especially those who are under immunosuppressive treatment. Moreover, following the emergence of several COVID vaccines, there are concerns regarding vaccine effectiveness and possible side effects in such patients. In this context, we tried to briefly summarize the accumulating evidence and recommendations for the management of IBD in the context of the COVID-19 pandemic.     

Fecal calprotectin correlated with endoscopic remission for Asian inflammatory bowel disease patients

AIM: To evaluate the correlation between fecal calprotectin (fC), C-reactive protein (CRP), and endoscopic disease score in Asian inflammatory bowel disease (IBD) patients.METHODS: Stool samples were collected and assessed for calprotectin levels by Quantum Blue Calprotectin High Range Rapid test. Crohn’s disease endoscopic index of severity (CDEIS) and ulcerative colitis endoscopic index of severity (UCEIS) were used for endoscopic lesion scoring.RESULTS: A total of 88 IBD patients [36 patients with Crohn’s disease (CD) and 52 with ulcerative colitis (UC)] were enrolled. For CD patients, fC correlated with CDEIS (r = 0.465, P = 0.005) and CRP (r = 0.528, P = 0.001). fC levels in UC patients correlated with UCEIS (r = 0.696, P < 0.0001) and CRP (r = 0.529, P = 0.0005). Calprotectin could predict endoscopic remission (CDEIS < 6) with 50% sensitivity and 100% specificity (AUC: 0.74) in CD patients when using 918 μg/g as the cut-off. When using 191 μg/g as the cut-off in UC patients, calprotectin could be used for predicting endoscopic remission (UCEIS < 3) with 88% sensitivity and 75% specificity (AUC: 0.87).CONCLUSION: fC correlated with both CDEIS and UCEIS. fC could be used as a predictor of endoscopic remission for Asian IBD patients.     

Hepatitis B vaccination in patients with inflammatory bowel disease

AIM: To determine the prevalence for hepatitis B virus (HBV) and HBV screening and vaccination practices for inflammatory bowel disease (IBD).METHODS: This study is a retrospective, cross-sectional observational study. A retrospective chart review was performed in 500 patients who have been consecutively treated for IBD between September 2008 and January 2013 at the Rush University Medical Center Gastroenterology section. The patients were identified through the electronic medical record with the criteria that they attended the gastroenterology clinic, and that they had a diagnosis of IBD at the time of visit discharge. Once identified, each record was analyzed to determine whether the subject had been infected with HBV in the past, already been vaccinated against HBV, or advised to get vaccinated and followed through with the recommended vaccination.RESULTS: About 254 out of 500 patients (51%) had HBV screening ordered. Among those ordered to have screening tests, 86% followed through with HBV serology. Gastroenterology physicians had significantly different screening ratios from each other (P < 0.001). There were no significant differences in the ratios of HBV screening when IBD specialists were compared to other gastroenterology physicians (0.505 ± 0.023 vs 0.536 ± 0.066, P = 0.66). Of those 220 patients screened, 51% of IBD patients were found not to be immune against HBV. Approximately 50% of gastroenterology physicians recommended HBV vaccinations to their patients in whom serology was negative for antibodies against HBV. IBD specialists recommended vaccinations to a higher percentage of their patients compared to other gastroenterology physicians (0.168 ± 0.019 vs 0.038 ± 0.026, P = 0.015). Present and/or past HBV infection was found in 3.6% of the patients who had serology checked. There was no statistically significant difference in the prevalence of hepatitis B surface antigen (HBsAg) between our study and that reported in previous studies done in Spain (4/220 vs 14/2076 respectively, P = 0.070); and in France (4/220 vs 3/315 respectively, P = 0.159). But, the prevalence of anti-HBcAb in this study was less than that reported in the study in Spain (7/220 vs 155/2076 respectively, P = 0.006); and was not significantly different from that reported in the study in France (7/220 vs 8/315 respectively, P = 0.313).CONCLUSION: The prevalence of HBsAg in our IBD patients was not higher than previously reported European studies. Most IBD patients are not routinely screened or vaccinated against HBV at a tertiary referral center in the United States.     

Mucocutaneous Manifestations and Associated Factors in Patients with Crohn’s Disease

Background:One-third of all extraintestinal manifestations are mucocutaneous findings in patients with Crohn’s disease and there is a relationship between some risk factors. Our aim is to evaluate factors associated with mucocutaneous manifestations in our cohort of patients with Crohn’s disease with a follow-up duration of up to 25 years.Methods:In the study, 336 patients with Crohn’s disease who were followed up between March 1986 and October 2011 were included. The demographic characteristics, Crohn’s disease-related data, and accompanying mucocutaneous manifestations were recorded. The cumulative probability of mucocutaneous extraintestinal manifestations and possible risk factors were analyzed.Results:Oral and skin involvement were detected in 109 (32%) and 31 (9.2%) patients, respectively. The cumulative probability of developing oral and skin manifestations were 43.2% and 20.3%, respectively. Cox regression analysis showed that female gender (odds ratio: 3.28, 95% CI: 1.51-7.14, P = .003) and corticosteroid use (odds ratio: 7.88, 95% CI: 1.07-57.97, P = .043) are independently associated with the development of skin manifestations, while family history (odds ratio: 3.59, 95% CI: 2.18-5.93, P < .001) and inflammatory-type disease (odds ratio: 1.776, 95% CI: 1.21-2.61, P = .004) were independently associated with the development of oral ulcers.Conclusion:Mucocutaneous extraintestinal manifestations are associated with female gender, corticosteroid use, family history, and disease type in a large cohort of patients with Crohn’s disease. Defining the specific relationships of immune-mediated diseases will help to better understand the pathogenesis of Crohn’s disease and associated mucocutaneous manifestations and to use more effective treatments.     

Extraintestinal manifestations in a large series of Italian inflammatory bowel disease patients

AIM: To investigate prevalence, type and time of onset of extraintestinal manifestations (EIMs) in a series of Italian inflammatory bowel disease (IBD) patients.METHODS: Data of 811 IBD consecutive patients, first referred to our Centre from 2000 to 2011, were retrospectively evaluated.RESULTS: Eight hundred and eleven IBD patients (437 M, 374 F) were studied: 595 ulcerative colitis (UC) (73.4%) and 216 Crohn’s disease (CD) (26.6%). Among these, 329 (40.6%) showed EIMs: 210 UC (35.3%) and 119 CD (55.1%) (P < 0.0001). Considering the time of the diagnosis of IBD, 37 EIMs (11.2%) were developed before, 229 (69.6%) after and 63 (19.2%) were simultaneous. The type of EIM were as follows: 240 musculoskeletal (29.6%), in 72 CD patients and in 168 UC (P < 0.0001); 47 mucocutaneous (5.8%), in 26 CD and in 21 UC (P = 0.0049); 26 ocular (3.2%), in 16 CD and in 10 UC (CD 7.4% vs UC 1.7%, P = 0.0093); 6 hepatobiliary (0.8%); 10 endocrinological (1.2%). In particular, with regards to the involvement of the musculoskeletal system, arthritis Type 1 was found in 41 CD (19%) and in 61 UC (10.2%) (P = 0.0012) and Type 2 in 25 CD (11.6%) and in 100 UC (16.8%) (P = 0.0012).CONCLUSION: Mucocutaneous manifestations, arthritis Type 1 and uveitis were significantly more frequent in CD than UC. The complications of the musculoskeletal system were the mostly observed ones, often with symptoms more severe than intestinal ones, confirming the need for close cooperation with rheumatologists.     

Interaction of obesity and inflammatory bowel disease

Inflammatory bowel disease (IBD) is a chronic inflammatory condition of unknown etiology that is thought to result from a combination of genetic, immunologic and environmental factors. The incidence of IBD has been increasing in recent decades, especially in developing and developed nations, and this is hypothesized to be in part related to the change in dietary and lifestyle factors associated with modernization. The prevalence of obesity has risen in parallel with the rise in IBD, suggesting a possible shared environmental link between these two conditions. Studies have shown that obesity impacts disease development and response to therapy in patients with IBD and other autoimmune conditions. The observation that adipose tissue produces pro-inflammatory adipokines provides a potential mechanism for the observed epidemiologic links between obesity and IBD, and this has developed into an active area of investigative inquiry. Additionally, emerging evidence highlights a role for the intestinal microbiota in the development of both obesity and IBD, representing another potential mechanistic connection between the two conditions. In this review we discuss the epidemiology of obesity and IBD, possible pathophysiologic links, and the clinical impact of obesity on IBD disease course and implications for management.     

Fecal calprotectin in predicting small bowel capsule endoscopy findings in pediatric patients with known Crohn’s disease

Fecal calprotectin (FC) has been proposed as a noninvasive surrogate marker of intestinal inflammation in inflammatory bowel disease. This study aimed to assess the capability of FC in predicting small bowel capsule endoscopy (SBCE) findings in pediatric patients with known Crohn’s disease (CD). We retrieved data of consecutive patients aged 2 to 17 years old with established CD who underwent SBCE from Janurary 2017 to April 2020 and had endoscopic remission on ileocolonoscopy. Sixty-eight patients were included in the analysis. There were 13 patients with a weighted pediatric CD activity index ≥ 12.5, 47 patients with FC ≥ 200 µg/g, and 45 patients with significant small bowel (SB) inflammation [Lewis score (LS) ≥ 135]. The LS correlated weakly with FC (R = 0.30, P < .05). The area under the curve of FC as a surrogate diagnostic test for LS ≥ 135 was 0.691, and the optimal FC cutoff values were 242 µg/g with the corresponding sensitivity and specificity of 78% and 65%, respectively. The area under the curve of FC for moderate-to-severe inflammatory activity in the SB was 0.718. In patients with FC level ≥ 670 µg/g, LS ≥ 790 was found in 33% (9/27) of patients, with the sensitivity and specificity of 69% and 67%, respectively. FC may be used to predict SB mucosal inflammation in pediatric patients with confirmed CD having endoscopic remission on ileocolonoscopy.     

Continuing low incidence of Crohn’s disease in Northwest Greece

AIM OF STUDY: The largest population-based study for inflammatory bowel disease in Northwest Greece. MATERIALS AND METHODS: A retrospective survey for the years 1982-1997. RESULTS: Of 400 patients, 334 had ulcerative colitis, 43 Crohn's disease and 23 indeterminate colitis. CONCLUSIONS: Crohn's disease still remains rare in Northwest Greece.     

Parenteral Methotrexate Is Efficient in the Treatment of Azathioprine Refractory Crohn’s Disease

BackgroundThere is limited data in the literature analyzing the efficacy of methotrexate in Crohn’s disease used after thiopurine analogs. We aimed in our study to show the efficacy of methotrexate in Crohn’s disease patients who failed to respond to thiopurine treatment.MethodsThe study included 29 azathioprine refractory patients with Crohn’s disease. Intramuscular methotrexate (25 mg/week) in the induction of remission and intramuscular methotrexate (15 mg/week) in 29 CD patients with a median follow-up time of 13 months was performed. In 15 (51.7%) patients, methotrexate was used in combination with anti-Tumour necrosis factor (TNF) (combination group), while it was used in 14 (48.3%) patients in monotherapy (monotherapy group).ResultsThe mean Harvey–Bradshaw index score significantly decreased in the follow-up period (Wk0 = 7.6, last visit = 4.5, P < .001). Remission and response rates at week 12 were 75.9% and 79.3%, respectively. Maintenance of remission (77.8% vs 37.5%, respectively, P = .1) and response rates (77.8% vs 50%, respectively, P = .3) due to last visit examination were numerically higher in combination group but they were not statistically significant. The cumulative probability of remission maintenance in patients with methotrexate therapy was 72.7%, 33.1%, and 22.0% at 1, 2 ,and 4 years after starting methotrexate, respectively.ConclusionOur results show that parenteral use of methotrexate is efficacious in inducing and maintaining remission as a step-up agent in azathioprine refractory Crohn’s disease patients.