Adalimumab Drug Levels at Secondary Loss of Response Do Not Predict Response to Dose-intensification in Crohn's Disease: A Retrospective, International Multicenter Study.

BACKGROUND: The exposure-response relationship is less established for adalimumab (ADA) compared with infliximab in inflammatory bowel disease (IBD). Evidence supporting therapeutic drug monitoring post dose-intensification of ADA is limited. We aimed to explore the association between ADA drug levels and Crohn's disease (CD) activity at loss of response, and at 6 and 12 months post dose-intensification. METHODS: We performed a retrospective study of adult patients with CD receiving dose-intensified weekly ADA following secondary loss of response at 3 tertiary centers across 5 years. ADA trough levels were analyzed using a drug-sensitive enzyme-linked immunosorbent assay at loss of response, and 6 and 12 months after dose-intensification. Rates of clinical remission, objective remission (C-reactive protein <5 mg/L, fecal calprotectin <150 µg/g, or absence of inflammation at endoscopy or imaging), and ADA failure were investigated. RESULTS: A total of 131 CD patients were included, with a median disease duration of 9 (interquartile range, 4-17) years. 51% were biologic exposed prior to ADA and 50% received concomitant immunomodulators. Baseline drug levels measured at secondary loss of response did not discriminate between subsequent responders and non-responders at either 6 or 12 months post dose-intensification. However, both higher drug levels at 6 and 12 months and a higher increment from baseline were associated with improved outcomes. On receiver-operating characteristic analyses, post-escalation ADA drug levels >10.7 µg/mL (area under the receiver-operating characteristic curve [AUROC], 0.66; P = .013) and >10.9 µg/mL (AUROC, 0.67; P = .032) were associated with objective remission at 6 and 12 months, respectively. CONCLUSIONS: Drug levels following dose-intensification rather than at the time of secondary loss of response were associated with subsequent CD remission.

Literature supporting therapeutic drug monitoring at secondary loss of response and post dose-intensification of adalimumab is limited. Adalimumab drug levels following dose-intensification rather than at the time of secondary loss of response are associated with subsequent Crohn's disease remission.

Mind the gap: avoiding paravalvular leak using computer simulation in bicuspid transcatheter aortic valve replacement-a case report.

Background: Transcatheter aortic valve replacement (TAVR) is becoming increasingly prevalent worldwide and is now more common than surgical aortic valve replacement. It is expanding into all patient subsets including younger and lower risk patients. Bicuspid aortic valve (BAV) accounts for a significant proportion of TAVR, but due to heterogenous anatomy, it is of increased complexity. One of the greatest challenges in BAV is the selection of the correct TAVR size. Transcatheter aortic valve replacement sizing is based upon computed tomography-derived annular measurements. There are a number of sizing algorithms for BAV based upon anatomical characteristics, often yielding different results. This is noted especially when a patient falls near the borderline between two valve sizes, an anatomical grey zone. Complementary to the algorithm approach is the use of pre-procedural patient-specific computer simulation using finite-element modelling. Case summary: An 86-year-old female was treated for heart failure secondary to severe and calcific BAV aortic stenosis with TAVR. Due to anatomical difficulty and grey-zone valve sizing, we demonstrate the use of pre-procedural patient-specific computer simulation with the novel Medtronic Evolut PRO+ platform to achieve a good result. Discussion: Using patient-specific computer simulation, we were able to safely select the valve and the deployment height and then accurately predict the result in a difficult, severely calcified BAV. In addition to improving outcome, this allows for patient-specific, tailored discussion to occur at heart team meetings.

The role of exclusive enteral nutrition in the pre-operative optimisation of adult patients with Crohn's disease. A systematic review.

AIM: To conduct a systematic review in order to bring together the current knowledge about the use of exclusive enteral nutrition (EEN) in the pre-operative optimisation of adult patients with Crohn's disease undergoing intestinal resection. METHODS: We searched Pubmed, Cochrane Library, ClinicalTrials.gov and the EU clinical trial register to identify experimental and observational studies on the effect of pre-operative EEN on nutritional and clinical outcomes of patients undergoing surgery. Methodological quality was assessed using the Downs and Black checklist. RESULTS: Seven studies were included in the final analysis. Of these 5 were retrospective cohort studies and 2 were retrospective case-control studies. There were 4 ongoing RCTs, however they have not reported data to analyse. Overall the 7 retrospective studies, support that with EEN; body mass index (BMI) does not increase, C-reactive protein decreases (CRP), albumin usually increases and haemoglobin does not significantly change. There were fewer infectious complications in patients who had taken EEN. There was a trend towards fewer stomas but only one of the studies was powered enough to demonstrate significance. There was no significant difference in recurrence rates of Crohn's disease at 12 months in any of the studies. Quality of the studies were either medium or poor. CONCLUSION: The current data on the use of EEN in pre-operative optimisation is of poor quality and underpowered to demonstrate significance. Randomised controlled trials are needed to demonstrate whether or not EEN can improve outcomes and reduce stoma formation in adult patients undergoing intestinal resection.

Does exclusive enteral nutrition reduce the rate of stoma formation in patients requiring ileocolic resection for Crohn's disease? A single center experience.

BACKGROUND AND AIM: Nutrition has a role in achieving and maintaining remission in Crohn's disease. The aim of this study was to determine the impact of a strategy of steroid-avoidance and Exclusive Enteral Nutrition (EEN) for 6 weeks (with a minimum of 4 weeks) in adult patients presenting with acute small bowel Crohn's disease followed by an interval ileocolic resection 4-6 weeks later. METHODS: Retrospective review of prospectively collected data. Patients were administered exclusive enteral nutrition (EEN) for at least 4 weeks prior to surgery. RESULTS: 24 EEN patients included. Median age of 45 (range 23-73). 17/24 patients tolerated Modulen for at least 4 weeks, 5 were switched to Ensures and 2 a liquid diet. 6 patients underwent surgery earlier than planned. Prior to surgery, there was no change in the mean BMI, albumin increased from a mean of 36 g/L (range 25-43) to 40 g/L (range 30-48). CRP levels decreased by a mean of 35.8 mg/L overall. 19 (79%) of operations were performed laparoscopically. 6 of the cases were re-do operations. All but 3 patients avoided a stoma at the time of the original operation. There were 5 post-operative complications: 1 anastomotic leak in a patient with a BMI of 42, 3 cases of paralytic ileus and 2 wound infections. Median length of stay was 7 days (range 3-76 days). Only 2 patients were readmitted within the 30-day post-operative period. CONCLUSION: The pre-operative use of EEN appears to avoid unnecessary stoma formation with acceptable clinical outcomes.

Managing appendicitis during the COVID-19 era: A single centre experience & implications for future practice.

AIM: During the COVID-19 pandemic, emergency surgery was modified in line with Royal College guidance to accommodate the evolving climate. This study compared management of appendicitis before and during the pandemic by assessing disease presentation severity, modes of investigation, surgical management and patient outcomes. Outcomes assessed included length of stay, readmissions and rates of postoperative wound infections. METHODS: We collected data on appendicitis patients managed at a district general hospital over two distinct 8-week periods; 42 patients before and 36 patients during the COVID-19 pandemic respectively. The study included clinically or radiologically diagnosed appendicitis patients. RESULTS: Our study found patients during the COVID-19 pandemic had higher inflammatory markers (CRP 103 vs 53 mg/L; p = 0.03) and more severe disease on histological examination of the appendix than pre-pandemic. Patients were nearly twice as likely to undergo CT diagnosis of appendicitis during the pandemic than before. During the pandemic, only half of the cohort underwent laparoscopic appendicectomy in contrast with greater than 85% of the pre-COVID-19 cohort (p = 0.0005). Patients in the COVID-19 era cohort recorded shorter lengths of hospital stay (2.6 vs 3 days; p = 0.35); however, had higher reattendance rates (12 vs 25%; p = 0.15) and surgical site infections (p = 0.0443). Finally, the study reported shorter median time to theatre (0 vs 1 days) during the pandemic than before. CONCLUSION: In addition to reiterating the benefits of laparoscopic versus open surgery and quicker diagnostic methods, this study also implies that though patients during COVID-19 era presented with more severe disease, their treatment was in a more efficient service.