Vitamin D and Ulcerative Colitis: Is There a Relationship with Disease Extent?

INTRODUCTION: Patients with ulcerative colitis (UC) can suffer from low serum vitamin D that can result in complications such as low bone mineral density. It can also reflect underlying disease severity. METHODS: One hundred and ninety-seven patients previously diagnosed with UC from 2 European centers were prospectively recruited through the out-patient clinics. Clinical features (Montreal Classification, age, gender, previous and current medications, surgery), disease activity (Simple Clinical Colitis Activity Index [SCCAI]), blood investigations including serum inflammatory markers, and serum vitamin D were analyzed. The vitamin D levels were compared to a group of age- and gender-matched healthy controls. RESULTS: Mean vitamin D levels were lower in patients with UC (54.6 nmol/L) than in controls (80.7 nmol/L; p = 0.0001). Mean vitamin D levels was lowest in patients with extensive UC (E3; p = 0.0001). Serum vitamin D was not significantly different across treatment groups (p = 0.876). There was no statistical difference in vitamin D levels across patients receiving calcium and vitamin D supplements (p = 0.35) and there was no statistical correlation with SCCAI (p = 0.22). CONCLUSIONS: This study confirms the existence of low serum vitamin D in patients with UC when compared to healthy controls. It also provides evidence of an existing relationship between disease extent and serum vitamin D.

The role of small-bowel endoscopy in inflammatory bowel disease: an updated review on the state-of-the-art in 2021.

The impact of small-bowel (SB) capsule endoscopy and device-assisted enteroscopy on clinical practice, since their introduction 2 decades ago, has been remarkable. These disruptive technologies have transformed the investigation and management of SB pathology and now have a firmly established place in guidelines and clinical algorithms. Furthermore, recent years have witnessed innovations, driven by the demand of new goals in the management of inflammatory bowel disease (IBD), such as mucosal healing and evolving strategies based on tight monitoring and accelerated escalation of care. These developments in SB endoscopy have also been paralleled by refinement in dedicated radiological SB imaging technologies. This updated review highlights the current state of the art and more recent innovations with a focus on their role in IBD.

Impact of simple, specific, verbal instructions on the quality of bowel preparation in hospitalized patients undergoing colonoscopy: a multicenter randomized controlled trial.

Background and study aims Bowel preparation for colonoscopy is frequently inadequate in hospitalized patients. We explored the impact of specific verbal instructions on the quality of inpatients bowel preparation and factors associated with preparation failure. Patients and methods Randomized (1:1), two strata (mobilized vs. bedridden; 3:2) trial of consecutive inpatients from four tertiary centers, who received either specific, verbal instructions or the standard of care (SOC) ward instructions about bowel preparation. The rate of adequate bowel preparation (Boston Bowel Preparation Score [BBPS] ≥ 6, no segment < 2) comprised the primary endpoint. Mean BBPS score, good (BBPS score ≥ 7, no segment score < 2) and excellent (BBPS = 9) were among secondary endpoints. Results We randomized 300 inpatients (180 mobile) aged 71.7 ±â€Š15.1 years in the intervention (49.7 %) and SOC (50.3 %) groups, respectively. Overall, more patients in the intervention group achieved adequate bowel preparation, but this difference did not reach statistical significance neither in the intention-to-treat [90/149 (60.4 %) vs. 82/151 (54.3 %); P  = 0.29] nor in the per-protocol analysis [90/129 (69.8 %) vs. 82/132 (62.1 %); P  = 0.19]. Overall BBPS score did not differ statistical significantly in the two groups, but the provision of specific verbal instructions was associated with significant higher rates of good (58.1 % vs. 43.2 %; P  = 0.02) and excellent (31.8 % vs. 16.7 %; P  = 0.004) bowel preparation compared to the SOC group. Administration of same-day bowel preparation and patient American Society of Anesthesiologists score > 2 were identified as risk factors for inadequate bowel preparation. Conclusions Provision of specific verbal instructions did not increase the rate of adequate bowel preparation in a population of mobilized and bedridden hospitalized patients.

Endoscopy during the peak of COVID-19 pandemic: impact on activity and financial implications for a tertiary referral center in London.

BACKGROUND: COVID-19 pandemic is an unprecedented global medical emergency. National and international gastrointestinal societies recommended that any endoscopic activity during the lockdown phase of the pandemic should be limited to emergency or non-deferrable procedures only. We assessed the financial implications and impact on endoscopy activity of the lockdown phase in a tertiary referral endoscopy unit. METHODS: The number of endoscopy procedures canceled and performed in our endoscopy unit during our "delay phase" (16-22/03/2020) and "lockdown phase" (23/03-29/05/2020) was reviewed and compared with endoscopy activity conducted during the same period in 2019. The financial impact was subsequently analyzed. RESULTS: Between 16/03/2020 and 29/05/2020, 683 procedures were canceled and 365 non-deferrable procedures were performed. In contrast, in 2019, 3437 procedures were performed over the same timeframe, resulting in a revenue contraction of approximately €2,062,857. We estimated that the number of lists required to recuperate the canceled endoscopic activity, ranges from 103-155, depending on the level of personal protective equipment required and mitigating policy relating to COVID-19. CONCLUSION: Our results highlight that COVID-19 pandemic had a substantial negative impact on our endoscopy activity and on the revenue generated by our endoscopy unit.

Clostridium Difficile Infection in Patients Impact Suspected Cytomegalovirus Infection in Patients with Inflammatory Bowel Disease.

INTRODUCTION: Clostridium difficile infection (CDI) has been reported to be a cause of flare-ups in patients with inflammatory bowel disease (IBD). Cytomegalovirus (CMV) infection can cause severe disease and complications in immunocompromised patients in consequence of disease or therapy. AIM: Our aim was to describe the prevalence and clinical outcomes of CDI with concomitant CMV infection in IBD patients hospitalized for flare-ups in association with the disease itself and medication used. METHODS: We prospectively identified consecutive patients referred for CDI management during 2015-2017. Stool samples were tested for Clostridium difficile toxin A and/or B and Glutamate Dehydrogenase in patients with clinical symptoms. CDI patients with IBD history were tested for anti-CMV IgG and IgM antibodies by chemiluminescent microparticle immunoassay and underwent histological analysis for CMV on colon biopsies. Data were collected for demographic characteristics, treatment and outcome. RESULTS: 125 patients with CDI were enrolled. Among these patients, 14 (11.2%) were diagnosed with IBD. The mean patient age of IBD patients was 52.5±15.4 years at diagnosis of CDI, 85.7% had UC, 14.3% CD, while the age of patients was shared. Eleven of the total of 14 patients (78.6%) tested positive for anti-CMV IgG. Of these, 3 patients (21.4%) exhibited high CMV IgG avidity, without detectable anti-CMV IgM and biopsy-proven CMV colitis. Of the 14 IBD patients with CDI, 8 patients (57.1%) were receiving anti-tumor necrosis factor (anti-TNF) therapy (21.4 % infliximab or golimumab, 7.1% vedolizumab or adalimumab) and 43.5% of patients were being treated with systemic corticosteroids. Four UC patients (28.6%) on steroids of the 14 CDI patients underwent a colectomy whereas none of the not on steroids patients underwent colectomy (p=0.25). Among them, 1 patient (7.1%) had recurrent CDI after 5 months from the first episode of CDI.These patients were treated with vancomycin, metronidazole and fidaxomicin. The mean age of patients that had a colectomy 65.5±9.32 (n=4) was higher than the mean age of those 47.30±14.49 (n=10) who improved (UMann-Whitney=6. p=0.04). CONCLUSIONS: Immunosuppressive medications and older age are associated with increased risk of CDI and poor outcome. Although, CMV is a rare colonic pathogen in the immunocompetent patient, it should be included and screened when exacerbation of IBD occurs in patients receiving any type of immunosuppressive therapy.

Serum Bile Acids Profiling in Inflammatory Bowel Disease Patients Treated with Anti-TNFs.

BACKGROUND: Inflammatory bowel diseases (IBD), ulcerative colitis (UC), and Crohn's disease (CD), represent systematic chronic conditions with a deficient intestinal absorption. We first attempt to investigate the serum bile acids (sBAs) profile in a large cohort of IBD patients to evaluate changes under anti-TNF alpha treatment. METHODS: Forty CD and 40 UC patients were enrolled and BAs were quantified by high-pressure liquid chromatography-electrospray-tandem mass spectrometry (HPLC-ES-MS/MS). Up to 15 different sBAs concentrations and clinical biomarkers where added to a Principal Component Analysis (PCA) to discriminate IBD from healthy conditions and treatment. RESULTS: PCA allowed a separation into two clusters within CD (biologic-free patients and patients treated with anti-TNF alpha drugs and healthy subjects) but not UC. The first included CD. CD patients receiving anti-TNF alpha have an increase in total sBAs (4.11 1.23 µM) compared to patients not exposed. Secondary BAs significantly increase after anti-TNF alpha treatment (1.54 0.83 µM). Furthermore, multivariate analysis based on sBA concentration highlighted a different qualitative sBAs profile for UC and CD patients treated with conventional therapy. CONCLUSION: According to our results, anti-TNF alpha in CD restores the sBA profile by re-establishing the physiological levels. These findings indicate that, secondary BAs might serve as an indirect biomarker of the healing process.

Specific Features of Patients With Inflammatory Bowel Disease and Primary Sclerosing Cholangitis.

Primary sclerosing cholangitis (PSC) is a chronic and progressive disease of the biliary tract. PSC is strongly associated with inflammatory bowel disease (IBD), mainly with ulcerative colitis, and most PSC patients have underlying IBD. The pathophysiological interactions between IBD and PSC are unclear, although it seems that the patients with IBD and PSC have a distinct phenotype. IBD with coexisting PSC is more extensive and is characterized by milder activity compared to IBD alone. The coexistence of PSC increases the risk for colorectal cancer in IBD patients and lifelong annual surveillance colonoscopy is recommended. Also, liver transplantation (LT) for PSC may affect the course of IBD. In addition, the management of IBD after LT includes many specific problems. On the other hand, the effect of IBD on the natural history of PSC appears to be milder. However, IBD may increase the risk of postsurgical complications after LT and is a risk factor for recurrent PSC after LT. Overall, the coexistence of IBD with PSC changes the management, natural history and prognosis of both diseases.

Association of clinical and inflammatory markers with small bowel capsule endoscopy findings in Crohn's disease.

BACKGROUND: Mucosal healing is an established treatment endpoint in Crohn's disease (CD). Still, clinical indices and inflammatory markers are used widely in CD surveillance. AIM: The aim of this study was to investigate the diagnostic performance as well as the relationship of C-reactive protein (CRP) and Crohn's Disease Activity Index (CDAI) with small bowel capsule endoscopy's (SBCE) inflammation scoring index, the Lewis Score (LS). PATIENTS AND METHODS: CDAI, CRP, and SBCE findings of 30 CD patients with isolated small bowel disease were retrieved from our academic institution patient records and were analyzed statistically. RESULTS: SBCE showed significant mucosal inflammation [mean (SD) LS: 1599 (1380)], in nine (60.0%) of 15 patients who were in both clinical and biochemical remission. CDAI and CRP showed a weak and moderate correlation with LS (r=0.317, P=0.088 and r=0.516, P=0.004, respectively). The diagnostic performance of CDAI and CRP in predicting mucosal inflammation was as follows: sensitivity 23.8 and 52.4%; specificity 100 and 66.7%; positive predictive value 100 and 78.6%; and negative predictive value 36.0 and 37.5%. The area under the curve toward endoscopic activity prediction was 0.70 and 0.69, respectively. CONCLUSION: Both CDAI and CRP underestimated endoscopic activity as expressed by the LS in a significant proportion of patients with quiescent disease.

Fast-track drug approval in inflammatory bowel diseases.

Fast-track drug designation of safe regimens represents an emerging method of development and approval of new medications targeting debilitating diseases including inflammatory bowel diseases (IBD). The goal of accelerated drug approval pathways is to shorten the time between application and approval of therapies that treat diseases with significant morbidity and mortality. Recently, fast-track drug approval approaches were supported by data deriving from central reading of images, a method of clinical data interpretation that has significantly benefited patients with gastrointestinal disorders. Biological agents and other emerging therapies in IBD represent "game-changing" or "treat-to-target" drugs and have satisfied quite successfully some of the patients' unmet needs. The development of biosimilars is an area where the Federal Drug Administration and the European Agency for Evaluation of Medicinal Products seem to have different approval processes. Biosimilars, including those for IBD, promise cost reductions and wide access to biologic therapies by patients, advantages similar to those already offered by generic drugs. Given the rapid development of IBD drugs and patients' needs, a consensus among the academic community, clinicians, researchers, sponsors, patients and regulatory authorities is required to standardize better the IBD trials and create a productive environment for fast-track approval of any "changing-game" IBD drug.

CD4 count remission hypothesis in patients with inflammatory bowel disease and human immunodeficiency virus infection: a systematic review of the literature.

BACKGROUND: Patients with inflammatory bowel disease (IBD) and human immunodeficiency virus (HIV) infection have shown controversial data concerning the remission hypothesis of IBD due to CD4 count depletion caused by HIV. The aim of our systematic review was to investigate the hypothesis whether low CD4 count due to HIV is related to IBD remission. METHODS: We systematically searched PubMed for studies reporting on HIV infection in IBD patients. We extracted characteristics of IBD and HIV disease course and CD4 counts. RESULTS: Thirteen papers (2 case-control studies, 2 case series, and 9 case reports) were eligible including 47 patients with IBD and HIV infection (43 male; 27 with Crohn's disease, 19 with ulcerative colitis, and 1 with indeterminate colitis). The IBD diagnosis criteria were heterogeneous among studies. Remission was reported for patients with IBD and HIV infection in 5 studies, including 4 case-control or case series and 1 case report. Four of 5 studies with IBD cases reported remission related to the CD4 count remission hypothesis but only 2 of them explicitly reported the CD4 count cut-off point (500 cells/µL and 200 cells/mm3 respectively). On the contrary, 7 case reports described an active IBD course or relapse even in patients under immunosuppression. CONCLUSIONS: Current literature cannot support or reject the CD4 count remission hypothesis in IBD patients with HIV infection. Prospective studies using uniform criteria on IBD and HIV disease course and CD4 counts are needed.