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Crohn's disease (CD) is a chronic inflammatory condition that affects the gastrointestinal tract. It is part of a spectrum of inflammatory Bowel Diseases (IBD). The disease is complex, characterized by significant inter and intra-individual heterogeneity, which contributes to a diverse and multifaceted portrayal of the disease. Consequently, applying specific and accurate treatment is challenging, and therapeutic success rates remain disappointing and insufficient. In recent years, significant advances in the therapeutic potential of CD have been made. Hope has been provided by these developments in the form of an expanding treatment toolkit. However, even with these beneficial adjustments, patients are frequently treated using an ineffective "one size fits all" treatment protocol, ultimately leading to a plateau in drug effectiveness and a decline in overall treatment success rates. Furthermore, with the advancement in the genome-wide association study, in combination with significant bioinformatic developments, the world of medicine has moved in the direction of personalized, tailored-treatment medicine, and this trend has not escaped the world of IBDs. Prediction models, novel biomarkers, and complex algorithms are emerging and inspiring optimism that CD patients will be treated with "precision medicine" in the near future, meaning that their treatments will be selected based on the patient's various unique features. In this review, we will outline the current diagnostic and therapeutic limitations that lead to a glass ceiling effect and thus send us in pursuit of discovering novel biomarkers. We will illustrate the challenges and difficulties in discovering relevant and innovative biomarkers and implementing them into everyday clinical practice. We will also heighten the progress made in practicing personalized medicine for CD patients and shed light on future directions and horizons. [ABSTRACT FROM AUTHOR]

Diagnosed VTE rates were similar between patients with an IBD-related and a non IBD-related hospitalization. In the last 20 years, the treatment and management of patients with Crohn's disease (CD) and ulcerative colitis (UC) have been revolutionized by the introduction of biological therapies and small molecules. Interestingly, in patients with UC, the dose intensification's requirement rate was significantly higher compared to CD perhaps due to disease severity and accelerated anti-TNF clearance in active UC, warranting higher drug concentrations. Overall, the studies in this Special Issue provide a comprehensive view on novel therapeutic strategies in IBD and will assist physicians in improving IBD care and attempt to tailor the right treatment for each patient. [Extracted from the article]

Background: The link between ankylosing spondylitis (AS) and inflammatory bowel disease (IBD) is well-established, with concurrent prevalence estimates ranging from 5–10%. However, there are still significant gaps in our understanding, and a comprehensive treatment guideline for these co-diagnosed patients has yet to be established. Our objective was to explore patterns of treatment alterations following the diagnosis of AS in patients previously diagnosed with IBD, and vice versa. Additionally, we sought to determine how these modifications influence clinical outcomes in both conditions. Methods: This retrospective data-based cohort study included patients with coexisting IBD and AS that were diagnosed between the years 2009–2022 and were followed by the gastroenterology and the rheumatology units of the Sheba Medical Center, Israel. The data were extracted from the electronic health record and included demographic information, medication history, treatment modification at the time of second diagnosis, and the characteristics and activity of both IBD and AS at the index time and at the 3-month mark. Results: The study included a total of 68 patients, with a male predominance (40 patients, 59%). The median age was 43 years (IQR 31–55) and 78% had Crohn's disease (CD). The median duration between the diagnosis of the first disease to the second one was 4 years (IQR 1–9.5). A significant proportion of patients (85%) underwent treatment modification at their second diagnosis. Out of the total cohort, 28% initiated biological therapy, 17.6% switched their biologic regimen, and 16.2% discontinued NSAIDS. Patients who underwent biologic modifications at time of the second diagnosis (the initiation/switch/augmentation of a concurrent regimen) experienced significantly higher rates of clinical improvement in either IBD or AS at the 90-day follow-up compared to patients who did not (68% vs. 32%, p = 0.004), and biologic modification was found to be an independent predictor for clinical improvement (OR 3.69, CI 1.08–12.58, p = 0.037). Conclusions: Our findings suggest that biologic therapy modification at the time of the second diagnosis was associated with a higher rate of improvement in AS/IBD at the 90-day follow-up. [ABSTRACT FROM AUTHOR]

Background: The effectiveness of anti-TNF or ustekinumab (UST) as a second-line biologic after vedolizumab (VDZ) failure has not yet been described. Aims and Methods: In this retrospective multicenter cohort study, We aim to investigate the effectiveness of anti-TNF and UST as second-line therapy in patients with Crohn's disease (CD) who failed VDZ as a first-line treatment. The primary outcome was clinical response at week 16–22. Secondary outcomes included the rates of clinical remission, steroid-free clinical remission, CRP normalization, and adverse events. Results: Fifty-nine patients who failed on VDZ as a first-line treatment for CD were included; 52.8% patients received anti-TNF and 47.2% UST as a second-line therapy. In initial period (Week 16–22), the clinical response and remission rate was similar between both groups: 61.2% vs. 68%, p = 0.8 and 48.3% vs. 56%, p = 0.8 on anti-TNF and UST therapy, respectively. Furthermore, in the maintenance period the rate was similar: 75% vs. 82.3%, p = 0.8 and 62.5% vs. 70.5%, p = 0.8, respectively. Of the patients, 12 out of the 59 stopped the therapy, without a significant difference between the two groups (p = 0.6). Conclusion: Second-line biological therapy after VDZ failure therapy was effective in >60% of the patients with CD. No differences in effectiveness were detected between the use of anti-TNF and UST as a second line. [ABSTRACT FROM AUTHOR]

(1) Background: Predicting which patients with upper gastro-intestinal bleeding (UGIB) will receive intervention during urgent endoscopy can allow for better triaging and resource utilization but remains sub-optimal. Using machine learning modelling we aimed to devise an improved endoscopic intervention predicting tool. (2) Methods: A retrospective cohort study of adult patients diagnosed with UGIB between 2012–2018 who underwent esophagogastroduodenoscopy (EGD) during hospitalization. We assessed the correlation between various parameters with endoscopic intervention and examined the prediction performance of the Glasgow-Blatchford score (GBS) and the pre-endoscopic Rockall score for endoscopic intervention. We also trained and tested a new machine learning-based model for the prediction of endoscopic intervention. (3) Results: A total of 883 patients were included. Risk factors for endoscopic intervention included cirrhosis (9.0% vs. 3.8%, p = 0.01), syncope at presentation (19.3% vs. 5.4%, p < 0.01), early EGD (6.8 h vs. 17.0 h, p < 0.01), pre-endoscopic administration of tranexamic acid (TXA) (43.4% vs. 31.0%, p < 0.01) and erythromycin (17.2% vs. 5.6%, p < 0.01). Higher GBS (11 vs. 9, p < 0.01) and pre-endoscopy Rockall score (4.7 vs. 4.1, p < 0.01) were significantly associated with endoscopic intervention; however, the predictive performance of the scores was low (AUC of 0.54, and 0.56, respectively). A combined machine learning-developed model demonstrated improved predictive ability (AUC 0.68) using parameters not included in standard GBS. (4) Conclusions: The GBS and pre-endoscopic Rockall score performed poorly in endoscopic intervention prediction. An improved predictive tool has been proposed here. Further studies are needed to examine if predicting this important triaging decision can be further optimized. [ABSTRACT FROM AUTHOR]

Episodes of acute ileitis or colitis have been associated with future development of inflammatory bowel diseases (IBD). Nevertheless, the rate of future IBD among patients diagnosed with signs or symptoms of acute bowel inflammation is unknown. We aimed to assess the risk of IBD development among patients presenting with signs or symptoms of ileitis or colitis. We searched for all patients that visited the emergency department (ED) and underwent abdominal computed tomography (CT) who were eventually diagnosed with IBD during gastroenterology follow-ups within 9 years from the index admission. Multivariable models identified possible predictors of patients to develop IBD. Overall, 488 patients visited the ED and underwent abdominal imaging with abnormal findings, and 23 patients (4.7%) were eventually diagnosed with IBD (19 Crohn's, 4 ulcerative colitis). Patients with a future IBD diagnosis were significantly younger (28 vs. 56 years, p < 0.001) with higher rates of diarrhea as a presenting symptom (17.4% vs. 4.1%, p = 0.015) compared to non-IBD patients. On multivariable analysis, age (p < 0.001), colitis (p = 0.004) or enteritis (p < 0.001) on imaging and a diagnosis of diarrhea in the ED (p = 0.02) were associated with development of IBD. Although alarming to patients and families, ED admission with intestinal inflammatory symptoms leads to eventual diagnosis of IBD in <5% of patients during long-term follow-up. [ABSTRACT FROM AUTHOR]

Background: Urinary tract infection (UTI) is the most common urologic complication among patients with inflammatory bowel disease (IBD). However, data regarding UTI outcomes in this population are scarce. We aimed to evaluate adverse outcomes of UTI among patients with IBD. Methods: This was a retrospective cohort study of consecutive adult patients who visited the emergency room (ER) at Sheba Medical Center due to a UTI between 2012 and 2018. Data included demographic and clinical variables. UTI cases were extracted using ICD-10 coding. Results: Of 21,808 (ER) visits with a UTI, 122 were IBD patients (Crohn's disease—52, ulcerative colitis—70). Contrary to non-IBD subjects, patients with IBD had higher rates of hospitalization, acute kidney injury (AKI) and 30 day-recurrent hospitalization (59.3% vs. 68.9%, p = 0.032; 4.6% vs. 13.9%, p < 0.001; 7.3% vs. 15.6%, p = 0.001, respectively). Among patients with IBD, advanced age (p = 0.005) and recent hospitalization (p = 0.037) were associated with increased risk for hospitalization, while hydronephrosis (p = 0.005), recent hospitalization (p = 0.011) and AKI (p = 0.017) were associated with increased 30-day recurrent hospitalization. Neither immunosuppressants nor biologics were associated with UTI outcomes among patients with IBD. Conclusions: Patients with IBD treated for a UTI had higher rates of hospitalization, AKI and 30-day recurrent hospitalization than non-IBD patients. No association was observed between immunosuppressants or biologics and UTI outcomes. [ABSTRACT FROM AUTHOR]

Infliximab and vedolizumab are effective treatments for inflammatory bowel disease (IBD), although associated with adverse events (AE). While low or non-existent drug levels and positive antidrug antibodies have been associated with therapeutic failure, there is no clear association between higher drug levels and AE. A cross-sectional study consisting of Crohn's disease (CD) and ulcerative colitis (UC) patients receiving infliximab or vedolizumab at the Sheba Medical Center was performed. Patients completed a questionnaire regarding AEs related to biological therapy. Serum trough levels obtained on the same day were analyzed. Objective measures of outcomes were retrieved from medical records. Questionnaires were completed by infliximab (n = 169) and vedolizumab (n = 88)-treated therapy patients. Higher infliximab levels were only numerically associated with the occurrence of at least one AE (p = 0.08). When excluding fatigue and abdominal pain, higher infliximab levels were statistically associated with the occurrence of at least one AE (p = 0.03). Vedolizumab drug levels > 18 μg/mL were also linked with the occurrence of more AEs. No specific association was observed between the increased levels of either infliximab or vedolizumab and specific AEs (neurological symptoms, upper GI symptoms, infectious complications, and musculoskeletal symptoms). As significant AEs are very rare, additional multi-center studies are required. [ABSTRACT FROM AUTHOR]

Loss of response to antitumor necrosis factor (anti-TNF) therapies in inflammatory bowel disease occurs in a high proportion of patients. Our aim was to evaluate the loss of response to anti-TNF therapy, considered as the need for dose intensification (DI), DI effectiveness and the possible variables influencing its requirements. Bibliographical searches were performed. Selection: prospective and retrospective studies assessing DI in Crohn's disease and ulcerative colitis patients treated for at least 12 weeks with an anti-TNF drug. Exclusion criteria: studies using anti-TNF as a prophylaxis for the postoperative recurrence in Crohn's disease or those where DI was based on therapeutic drug monitoring. Data synthesis: effectiveness by intention-to-treat (random effects model). Data were stratified by medical condition (ulcerative colitis vs. Crohn's disease), anti-TNF drug and follow-up. Results: One hundred and seventy-three studies (33,241 patients) were included. Overall rate of the DI requirement after 12 months was 28% (95% CI 24–32, I2 = 96%, 41 studies) in naïve patients and 39% (95% CI 31–47, I2 = 86%, 18 studies) in non-naïve patients. The DI requirement rate was higher both in those with prior anti-TNF exposure (p = 0.01) and with ulcerative colitis (p = 0.02). The DI requirement rate in naïve patients after 36 months was 35% (95% CI 28–43%; I2 = 98%; 18 studies). The overall short-term response and remission rates of empirical DI in naïve patients were 63% (95% CI 48–78%; I2 = 99%; 32 studies) and 48% (95% CI: 39–58%; I2 = 92%; 25 studies), respectively. The loss of response to anti-TNF agents―and, consequently, DI―occurred frequently in inflammatory bowel disease (approximately in one-fourth at one year and in one-third at 3 years). Empirical DI was a relatively effective therapeutic option. [ABSTRACT FROM AUTHOR]

Patients with Crohn's disease (CD) are frequently subject to symptoms causing them to seek medical care in emergency departments (ED). Recurrent ED visits are frequent after initial discharge. We aimed to identify the characteristics of patients with Crohn's who tend to have recurrent visits to the ED. We created an electronic data repository of all patients with inflammatory bowel diseases who visited the ED in our tertiary medical center during the period 2012–2018. For this study, we retrieved consecutive Crohn's patients who presented with CD-related symptoms to the ED and were eventually discharged. Patients who returned to the ED in 7 and 30 days were compared with those who did not. Overall, 2299 patients visited our ED with complaints related to Crohn's disease exacerbation or complication. A total of 1259 (60% of the adult patients) were admitted for hospitalization. Of the 632 (33%) who were discharged from the ED, 53 (8.4%) and 110 (17.4%) re-visited the ED, in 7 and 30 days from discharge, respectively. In multivariable analysis, tachycardia (odds ratio (OR) = 2.19, 95% confidence interval (CI): 1.11–4.33, p value = 0.02), elevated alkaline phosphatase (OR = 2.09, 95% CI: 1.07–4.07, p value = 0.02), and hyponatremia (OR = 2.52, 95% CI: 1.24–5.10, p value = 0.01) were associated with revisiting the ED within 7 days. Tachycardia (OR 2.88 (95% CI 1.33–6.2)), anemia (OR 2.44 (95% CI 1.24–4.8)), and elevated alkaline phosphatase (OR 2.68 (95% CI 1.25–5.78)) were independently associated with ED returns in 30 days. Knowing these risk factors may assist in minimizing the burden of recurrent ED visits among patients with CD. [ABSTRACT FROM AUTHOR]

The impact of COVID-19 on inflammatory bowel disease (IBD) patients under pharmacological immunosuppression is still not clearly understood. We investigated the incidence of COVID-19 and the impact of immunosuppression and containment measures on the risk of SARS-CoV-2 infection in a large IBD cohort, from a multicenter cohort from 21st of February to 30th of June, 2020. Ninety-seven patients with IBD (43 UC, 53 CD, one unclassified IBD) and concomitant COVID-19 over a total of 23,879 patients with IBD were enrolled in the study. The cumulative incidence of SARS-CoV-2 infection in patients with IBD vs. the general population was 0.406% and 0.402% cases, respectively. Twenty-three patients (24%) were hospitalized, 21 (22%) had pneumonia, four (4%) were admitted to the Intensive Care Unit, and one patient died. Lethality in our cohort was 1% compared to 9% in the general population. At multivariable analysis, age > 65 years was associated with increased risk of pneumonia and hospitalization (OR 11.6, 95% CI 2.18–62.60; OR 5.1, 95% CI 1.10–23.86, respectively), treatment with corticosteroids increased the risk of hospitalization (OR 7.6, 95% CI 1.48–40.05), whereas monoclonal antibodies were associated with reduced risk of pneumonia and hospitalization (OR 0.1, 95% CI 0.04–0.52; OR 0.3, 95% CI 0.10–0.90, respectively). The risk of COVID-19 in patients with IBD is similar to the general population. National lockdown was effective in preventing infection in our cohort. Advanced age and treatment with corticosteroids impacted negatively on the outcome of COVID-19, whereas monoclonal antibodies did not seem to have a detrimental effect. [ABSTRACT FROM AUTHOR]

Patients with inflammatory bowel disease (IBD) have a high risk of venous thromboembolism (VTE) events in both hospitalized patients and outpatients. Although thromboprophylaxis is recommended for hospitalized patients with IBD, implementation is not universal, especially for non IBD-related hospitalizations. Our objective was to present VTE and thromboprophylaxis adherence rates among hospitalized patients with IBD. An electronic data repository was created of all patients with IBD who visited the emergency department (ED) of our tertiary medical center between 2012 and 2018. The data included tabular variables and free-text physician records. We searched the data for VTE events, using ICD10 coding. Overall, there were 7009 ED visits of 2405 patients with IBD, 1556 (64.7%) with Crohn's disease (CD) and 849 (35.3%) with ulcerative colitis (UC). Thromboprophylaxis was administered in 463 hospitalizations (12.4% of IBD-related and 10.9% of non IBD-related hospitalizations, p = 0.13). Nineteen VTEs were diagnosed in the ED and seventeen were diagnosed during hospitalization (11 non IBD-related and 6 IBD-related hospitalizations, 0.6% and 0.28% respectively, p = 0.12). One patient died during hospitalization and an additional two in the 90 days post-discharge from hospitalization (unrelated to VTEs). In conclusion, thromboprophylaxis rates in hospitalized patients with IBD are low, despite possible implications and established guidelines. Thromboprophylaxis should be implemented in patients with IBD hospitalized for all indications. [ABSTRACT FROM AUTHOR]

Many questions remain unanswered regarding therapeutic drug monitoring (TDM) utility with thiopurines. This study aims to establish a relationship between thiopurines' metabolites and drug toxicity. We performed a systematic review with inclusion of studies evaluating the relationship between thiopurines' metabolites and drug toxicity. Meta-analysis of mean difference (MD), correlations and odds ratio (OR) was performed. We identified 21,240 records, 72 of which were eligible for meta-analysis. Levels of 6-thioguanine nucleotides (6-TGN) were higher in patients with leukopenia (MD 127.06 pmol/8 × 108 RBC) and gastrointestinal intolerance (MD 201.46 pmol/8 × 108 RBC), and lower in patients with hepatotoxicity (MD −40.6 pmol × 108 RBC). We established a significant correlation between 6-TGN and leukocytes (r = −0.21), neutrophils (r = −0.24) and alanine aminotransferase levels (r = −0.24). OR for leukopenia in patients with elevated 6-TGN was 4.63 (95% CI 2.24; 9.57). An optimal cut-off of 135 pmol/8 × 108 RBC for leukopenia was calculated (sensitivity 75.4%; specificity 46.4%). 6-methylmercaptopurine ribonucleotides (6-MMPR) were significantly associated with hepatotoxicity (MD 3241.2 pmol/8 × 108 RBC; OR 4.28; 95% CI 3.20; 5.71). Levels of 6-MMPR measured in the first 8 weeks of treatment were associated with leukopenia. We conclude that TDM could be used to prevent thiopurines' toxicity. As optimal metabolites level may vary according to indication, physicians may adapt posology to decrease toxicity without compromising efficacy. [ABSTRACT FROM AUTHOR]