Postoperative Ustekinumab Drug Levels and Disease Activity in Patients with Crohn's Disease.

AIMS: This study investigated how post-operative ustekinumab levels relate to surgery type, endoscopic, biochemical, and clinical outcomes in patients with Crohn's Disease. METHODS: A retrospective study of patients with Crohn's Disease with a disease-related operation between 2016 and 2022 assessed outcomes based on ustekinumab levels. Patients were included if they had an ustekinumab trough level within two years post-operatively. Patients were separated into groups based on whether their ustekinumab trough levels were adequate, defined as ≥ 4 µg/mL, or suboptimal < 4 µg/mL. A subset of patients with ustekinumab levels taken within two years both before and after surgery was compared to non-surgical treatment-escalated controls outside the initial patient set. Harvey-Bradshaw index was used to evaluate clinical disease activity. Rutgeert's and Simple Endoscopic Score for Crohn's Disease was used to evaluate endoscopic disease activity. C-reactive protein and fecal calprotectin values were collected to evaluate the molecular inflammatory disease state. CBC data were used to evaluate anemia. RESULTS: Forty-four patients were identified, which had ustekinumab levels after Crohn's Disease-related surgery. Twelve of these patients had pre-operative levels and were compared to 26 non-surgical treatment-escalated controls. No relationship between ustekinumab levels and endoscopic or clinical disease activity post-operatively was found. This also held true when looking at different surgery types. Adequate levels of ustekinumab post-operatively yielded lower risk of anemia. Surgery itself did not have an impact on ustekinumab levels. CONCLUSIONS: This study provided new insights into how post-operative ustekinumab levels impact several factors in patients having undergone Crohn's disease-related surgery.

Development of Shingles on Tofacitinib Despite Completion of Recombinant Varicella-Zoster Virus Vaccine Series.

Shingles, also known as herpes zoster, is caused by the reactivation of the varicella-zoster virus (VZV). The risk of developing shingles increases with age, as well as in patients with weakened immune systems. Tofacitinib is a reversible Janus kinase inhibitor that suppresses the immune system and is used to treat autoimmune diseases, such as ulcerative colitis. Recombinant VZV vaccine is recommended for individuals taking tofacitinib and is highly effective at reducing the risk of shingles. This case report describes a patient with severe, refractory ulcerative colitis who developed shingles while on tofacitinib, despite prior vaccination with the recombinant VZV vaccine.

The Role of Vitamin D in Patients with Inflammatory Bowel Disease Treated with Vedolizumab.

BACKGROUND: Many clinical factors can contribute to the efficacy of medical therapy in Inflammatory Bowel Disease (IBD). We assessed their effects on the efficacy of vedolizumab therapy in a cohort of patients with IBD. METHODS: We conducted a retrospective study on patients between 18 and 80 years of age with ulcerative colitis (UC) or Crohn's disease (CD) who were seen in the IBD program at Houston Methodist in Houston, TX and treated with vedolizumab for at least 6 months from 2018 to 2022. We investigated factors prior to the initiation of therapy that best predicted treatment response, with an emphasis on vitamin D levels and examined several variables including patients' demographics and clinical information on disease location and severity and nutritional status before and after the initiation of vedolizumab. Post-treatment data were gathered after a minimum of 6 months of vedolizumab therapy. The clinical parameters used for the study were the Harvey-Bradshaw Index for CD and the Activity Index for UC. RESULTS: There were 88 patients included in our study of whom 44 had CD and 44 had UC.; median age was 39.5 (31.0, 53.25) years; 34% patients were male; and 80.7% were Caucasian. All patients received an induction dosing of 300 mg vedolizumab at 0, 2, and 6 weeks then maintenance dosing as standard of care every 8 weeks. Among UC patients with vitamin D ≥ 30 ng/mL at the initiation of vedolizumab therapy, UC Endoscopic Index of Severity (UCEIS) scores after 6 months of therapy were significantly lower than in those who had low pre-treatment vitamin D levels (1.5 vs. 3.87, p = 0.037). After treatment, vitamin D levels improved more significantly in the higher pre-treatment vitamin D group, with a median level of 56 ng/mL, than in the lower pre-treatment vitamin D group, with a median level of only 31 ng/mL (p = 0.007). In patients with CD with vitamin D ≥ 30 ng/mL at the initiation of vedolizumab therapy, we found higher iron saturation (12 vs. 25%, p = 0.008) and higher vitamin B12 levels (433.5 vs. 885 pg/mL, p = 0.003) than in those with vitamin D < 30 ng/mL. After treatment, CD patients with high pre-treatment vitamin D levels had significantly higher vedolizumab levels (27.35 vs. 14.35 µg/mL, p = 0.045) than those with low pre-treatment vitamin D. Post-treatment scores and inflammatory markers in CD patients (HBI, CRP, ESR, and SES-CD) were lower in those who had lower baseline vitamin D. CONCLUSIONS: Our results show higher pre-treatment vitamin D levels predicted significant endoscopic improvement in patients with ulcerative colitis (UC). Improving vitamin D levels lowered C-reactive protein levels significantly in CD patients. Higher vitamin D levels were seen after treatment in both UC and CD patients. Vitamin D can play a role in clinical and endoscopic outcomes and should be assessed routinely and optimized in patients with IBD.

Bioactive polymeric materials and electrical stimulation strategies for musculoskeletal tissue repair and regeneration.

Electrical stimulation (ES) is predominantly used as a physical therapy modality to promote tissue healing and functional recovery. Research efforts in both laboratory and clinical settings have shown the beneficial effects of this technique for the repair and regeneration of damaged tissues, which include muscle, bone, skin, nerve, tendons, and ligaments. The collective findings of these studies suggest ES enhances cell proliferation, extracellular matrix (ECM) production, secretion of several cytokines, and vasculature development leading to better tissue regeneration in multiple tissues. However, there is still a gap in the clinical relevance for ES to better repair tissue interfaces, as ES applied clinically is ineffective on deeper tissue. The use of a conducting material can transmit the stimulation applied from skin electrodes to the desired tissue and lead to an increased function on the repair of that tissue. Ionically conductive (IC) polymeric scaffolds in conjunction with ES may provide solutions to utilize this approach effectively. Injectable IC formulations and their scaffolds may provide solutions for applying ES into difficult to reach tissue types to enable tissue repair and regeneration. A better understanding of ES-mediated cell differentiation and associated molecular mechanisms including the immune response will allow standardization of procedures applicable for the next generation of regenerative medicine. ES, along with the use of IC scaffolds is more than sufficient for use as a treatment option for single tissue healing and may fulfill a role in interfacing multiple tissue types during the repair process.

Review: Bioengineering approach for the repair and regeneration of peripheral nerve.

Complex craniofacial surgeries of damaged tissues have several limitations, which present complications and challenges when trying to replicate facial function and structure. Traditional treatment techniques have shown suitable nerve function regeneration with various drawbacks. As technology continues to advance, new methods have been explored in order to regenerate damaged nerves in an effort to more efficiently and effectively regain original function and structure. This article will summarize recent bioengineering strategies involving biodegradable composite scaffolds, bioactive factors, and external stimuli alone or in combination to support peripheral nerve regeneration. Particular emphasis is made on the contributions of growth factors and electrical stimulation on the regenerative process.

Polymeric ionically conductive composite matrices and electrical stimulation strategies for nerve regeneration: In vitro characterization.

Stem cell strategies and the use of electrical stimulation (ES) represent promising new frontiers for peripheral nerve regeneration. Composite matrices were fabricated by coating electrospun polycaprolactone/cellulose acetate micro-nanofibers with chitosan and ionically conductive (IC) polymers including, sulfonated polyaniline, and lignin sulfonate. These composite matrices were characterized for surface morphology, coating uniformity, ionic conductivity, and mechanical strength to explore as scaffold materials for nerve regeneration in conjunction with ES. Composite matrices measured conductivity in the range of 0.0049-0.0068 mS/m due to the uniform coating of sulfonated polymers on the micro-nanofibers. Thin films (2D) and composite fiber matrices (3D) of IC polymers seeded with human mesenchymal stem cells (hMSCs) were electrically stimulated at 0.5 V, 20 Hz for 1 h daily for 14 days to study the changes in cell viability, morphology, and expression of the neuronal-like phenotype. In vitro ES lead to changes in hMSCs' fibroblast morphology into elongated neurite-like structures with cell bodies for ES-treated and positive control growth factor-treated groups. Immunofluorescent staining revealed the presence of neuronal markers including ß3-tubulin, microtubule-associated protein 2, and nestin in response to ES. © 2018 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater 107B: 1792-1805, 2019.