Are the New Biologics Effective in the Management of Postoperative Crohn's Disease?

BACKGROUND: Despite the growing therapeutic armamentarium, at least half of the patients with Crohn's disease will require surgery during their lifetime. Current evidence for the prevention and treatment of postoperative Crohn's disease supports the use of anti-tumor necrosis factor agents with limited data about the use of the newer biologics, vedolizumab and ustekinumab. METHODS: We performed a systematic review of available data to determine the efficacy of the newer biologics in the management of postoperative Crohn's disease. We included noncomparative and comparative studies. The main outcomes of interest were clinical and endoscopic postoperative recurrence rates. RESULTS: The search strategy identified 1231 citations, with 32 eligible for review. Several studies showed that the postoperative Crohn's disease recurrence rates with the use of the newer biologics were comparable to previously published results with the use of anti-tumor necrosis factor agents, while other studies failed to show their efficacy. It is important to note that the studies were heterogeneous and included a relatively small sample size, making it difficult to draw a definite conclusion about the efficacy of the newer biologics in the management of postoperative Crohn's disease. CONCLUSION: The newer biologics do play a role in the management of postoperative Crohn's disease. After our review, we proposed an updated algorithm on the role of newer biologics in the approach to patients with postoperative Crohn's disease. Yet, until we have better-designed studies, their definite positioning remains to be determined.

Review of the literature showed some encouraging results on the effectiveness of vedolizumab and ustekinumab in the prevention and treatment of postoperative Crohn's disease. However, more controlled studies comparing the new biologic agents with anti-tumor necrosis factor agents are needed.

A critical review of ozanimod for the treatment of adults with moderately to severely active ulcerative colitis.

INTRODUCTION: Ozanimod is a sphingosine-1-phosphate (S1P) modulator that inhibits lymphocyte trafficking from lymph nodes to the circulation. It is approved by the US Food and Drug Administration (FDA) for the treatment of relapsing multiple sclerosis and most recently for the management of moderate-severe ulcerative colitis (UC). AREAS COVERED: Here we review the status of drugs approved for moderate-severe UC, the unmet needs in the management of UC, proposed mechanisms of action of S1P modulators, clinical data regarding ozanimod in UC, and emerging S1P modulators being evaluated in inflammatory bowel disease. EXPERT OPINION: Ozanimod is superior to placebo in inducing and maintaining clinical and endoscopic remission in UC. Adverse events include transient asymptomatic bradycardia, first-degree atrioventricular blocks, transient asymptomatic hepatotoxicity, macular edema in patients with preexisting risk factors, and increased risk of nasopharyngitis. Ozanimod is contraindicated in patients with clinically significant cardiovascular diseases, type II second-, or third-degree atrioventricular blocks, and females of childbearing age who do not use contraception. Ozanimod is the first S1P modulator to be approved for UC, offering a new therapeutic class option for patients. It has the advantages of being convenient with a once-daily oral administration, non-immunogenic, and overall safe when used in patients without contraindications.

First or Second Biologic in Inflammatory Bowel Disease: Combination Therapy or Monotherapy?

The therapeutic armamentarium for patients with inflammatory bowel disease has been expanding. Current guidelines make recommendations about whether patients who are biologic naive should be receiving biologic monotherapy or combination therapy, depending on the class of biologics. However, due to the limited available data, guidance to inform clinical practice for patients receiving their second or more biologic are lacking. We hereby review the available data about the use of biologic monotherapy or combination therapy with concomitant immunomodulator therapies in patients receiving their first as well as those receiving their second biologic.

Resuming aspirin in patients with non-variceal upper gastrointestinal bleeding: a systematic review and meta-analysis.

BACKGROUND: Our primary and secondary aims were to analyze the evidence surrounding mortality and re-bleeding risks in patients on aspirin with non-variceal upper gastrointestinal bleeding (NVUGIB) as a function of whether or not aspirin was resumed after the bleeding episode, and to determine whether aspirin intake upon admission affected the outcomes. METHODS: A search for randomized controlled trials (RCTs) and prospective observational studies was performed. Data extraction and risk of bias assessment were done. Generic inverse variance and random-effects model were employed. Heterogeneity across studies was assessed using the I 2 test. Certainty of evidence was assessed using the GRADE approach for each comparison and outcome, and an evidence profile was created. RESULTS: Evidence from 1 RCT and 4 observational studies suggests that early aspirin resumption reduced mortality (hazard ratio [HR] 0.20, 95% confidence interval [CI] 0.06-0.63) while increasing re-bleeding risk (HR 1.90, 95%CI 0.60-6.00); moderate certainty of evidence. The observational evidence was inconsistent for both mortality (HR 0.84, 95%CI 0.54-1.33) and re-bleeding (HR 0.85, 95%CI 0.47-1.55); very low certainty of evidence. Nine observational studies addressed our secondary aim: 6 provided inconsistent results regarding mortality (pooled odds ratio [OR] 1.1, 95%CI 0.80-1.50) and 4 provided inconsistent results regarding re-bleeding risk (pooled OR 0.92, 95%CI 0.53-1.59); very low certainty of evidence for both outcomes. CONCLUSION: Evidence supporting a protective effect of aspirin resumption soon after NVUGIB is of low-to-moderate certainty, and is not informative as to the optimal timing of aspirin resumption.

An Internal Medicine Intern Retreat to Facilitate Transition to PGME and Promote Peer Interaction.

BACKGROUND: Interns in the internal medicine program at American University of Beirut Medical Center (AUBMC) come from diverse educational backgrounds based on American, French, and Egyptian systems, similar to other settings in the Middle East. To help this diverse group of trainees integrate into their new role, the institution launched an intern retreat in 2014 and repeated the event 3 times to date. OBJECTIVE: We describe the experience with the AUBMC intern retreat and discuss the format and interns' perceptions of the benefits of the event. METHODS: The retreat was divided into workshops and team-building sessions. Workshop topics focused on communication, teamwork, time management, survival tips, patient-physician interaction, and resident well-being. Fun activities were meant to strengthen peer-to-peer relationship and included a treasure hunt, Jeopardy game, and basketball. RESULTS: Retreats took place in 2014, 2016, and 2017, and involved 72 of 102 interns (71%), as participation was optional. The 2015 retreat had to be canceled due to logistical problems. Of 72 eligible interns, 61 (85%) responded to the evaluation survey. The majority rated the activity as fun or interesting; sessions with the highest ratings included communication, patient-physician interaction, and resident well-being. There was unanimous agreement to make the retreat a yearly tradition. Each year, we collected feedback and made changes to further improve the retreat experience. CONCLUSIONS: The retreat is now an established activity. In an institution that accepts interns from different backgrounds, the retreat has strengthened peer-to-peer relations, improved communication, and contributed to a collegial and supportive work environment.

EFFICACY OF INTRAVITREAL RANIBIZUMAB INJECTIONS IN THE TREATMENT OF VITREOUS HEMORRHAGE RELATED TO PROLIFERATIVE DIABETIC RETINOPATHY.

PURPOSE: To investigate the efficacy of intravitreal ranibizumab injections in proliferative diabetic retinopathy associated with vitreous hemorrhage (VH). METHODS: A prospective study including patients with proliferative diabetic retinopathy who presented with persistent VH. Vitreous hemorrhage was graded into mild, moderate, and severe. Patients were randomized into two groups: the ranibizumab group was treated with intravitreal injections of ranibizumab and the control group was assigned to observation alone. Vitrectomy was performed if there was any aggravation of the VH in patients with mild, moderate, and severe VH or in the absence of improvement by 16 weeks in patients with moderate and severe VH. RESULTS: The ranibizumab group included 71 patients and the control group included 62 patients. There was a statistically significant difference in the vitrectomy rate in patients with mild-to-moderate VH (5 patients [7.04%] and 12 patients [19.35%], respectively; P = 0.04). However, there was no statistically significant difference in the overall vitrectomy rate, and in the vitrectomy rate in severe VH (17 [23.94%] and 12 [16.90%] patients in the ranibizumab group vs. 22 [35.48%] and 10 [16.13%] patients in the control group, P = 0.14 and P = 0.83, respectively). Recurrence of the VH occurred in 22 patients in the ranibizumab group and 29 patients in the control group (P = 0.06). Better visual acuity measurements were recorded on all follow-up visits in the ranibizumab group (P ≤ 0.04). CONCLUSION: Intravitreal ranibizumab injections could be considered in proliferative diabetic retinopathy patients with mild and moderate VH.

Use of Contrast-Enhanced Ultrasound for Confirmation of Central Venous Catheter Placement: Systematic Review and Meta-analysis.

OBJECTIVES: The purpose of this meta-analysis was to determine the sensitivity, specificity, and positive and negative predictive values of contrast-enhanced ultrasound (US) for confirming the tip location and placement of central venous catheters in adult patients. METHODS: A systematic review was performed using electronic databases, including MEDLINE, ClinicalTrials.gov, Cochrane, Embase, PubMed, and Scopus. Inclusion criteria were studies conducted on adult patients receiving an internal jugular or a subclavian central venous catheter in the emergency department or intensive care unit. Furthermore, the catheter tip location had to be checked with the use of the agitated saline contrast-enhanced US technique. RESULTS: A total of 2245 articles were screened by title and abstract. Seventeen articles were retrieved and assessed for the predefined inclusion criteria. Four articles and 1 abstract were used in the final analysis. Contrast-enhanced US showed pooled sensitivity of 72% (95% confidence interval, 44%-91%), pooled specificity of 100% (95% confidence interval, 99%-100%), a positive predictive value of 92.1%, and a negative predictive value of 98.5% compared with chest radiography for confirming the placement of central venous catheters. CONCLUSIONS: In the setting of central venous catheter placement, postprocedural contrast-enhanced US imaging is a safe, efficient, and highly specific confirmatory test for the catheter tip location compared with chest radiography.