Positioning risankizumab in the treatment algorithm of moderate-to-severe Crohn's disease.

Risankizumab is a humanized monoclonal antibody that inhibits the p19 subunit of IL-23 cytokine. Recently it has been approved for the treatment of patients with moderate-to-severe Crohn's disease (CD). We conducted a scoping review to summarize the available data on risankizumab and to define its positioning in the treatment algorithm of CD. Pubmed, Embase and Scopus databases were searched up to Oct 31, 2023 to identify studies reporting efficacy and safety data of risankizumab in patients with CD. Risankizumab is an effective and safe drug for the management of patients with moderate-to-severe CD. It could be used as first-line therapy in biologic-naive patients and in patients who have previously failed other biological therapies.

When we eat the food is processed and absorbed by the gastrointestinal tract. Sometimes, in some people, the gastrointestinal tract gets inflamed, causing problems like tummy ache and diarrhea: this condition is called Crohn's disease. To help turn off this inflammation and make people with Crohn's disease feel better, there's a new treatment called risankizumab. Risankizumab binds to the proteins in the body that cause inflammation and blocks their effects. This helps to reduce gastrointestinal inflammation and relieve its symptoms. Scientific studies have shown that is effective, safe, and it starts working quickly. Patients using this treatment do not have to go to the hospital every time. After three times in the outpatient's clinic, they can continue the treatment comfortably at home using a small device that sticks to the body and administers the medicine.

The role of filgotinib in ulcerative colitis and Crohn's disease.

Filgotinib is an oral small molecule that selectively inhibits JAK1. It is already approved for the treatment of moderately to severely active ulcerative colitis (UC). Ongoing studies are evaluating the efficacy and safety of filgotinib in Crohn's disease (CD). The purpose of this review is to summarize the available data regarding filgotinib in the management of UC and CD. We used Pubmed, Embase and clinicaltrials.gov websites to search all available data and currently ongoing studies regarding the efficacy and safety of filgotinib in inflammatory bowel diseases. Filgotinib is an effective and safe drug for the management of biologic-naive and biologic-experienced patients with moderate-to-severe UC. The same efficacy results have not been achieved in CD.

Filgotinib is an oral medication that inhibits the activity of the JAK1 enzyme. It has received approval from the European Medicines Agency for the treatment of moderate-to-severe ulcerative colitis, a condition characterized by inflammation in the lower part of the digestive tract. Filgotinib has a rapid mechanism of action and is effective at relieving the symptoms of ulcerative colitis and maintaining this improvement. However, its use is recommended with caution in patients who have risk factors such as heart and blood vessel issues, active smoking, a history of cancer, or those who are elderly (over 65 years old), and only when there are no other viable treatment options available. Although filgotinib was also studied for managing moderate-to-severe Crohn's disease, a chronic inflammatory condition affecting the digestive system, it did not pass phase III clinical trials and will not be available for this indication.

Translational Characterization of Macrophage Responses to Stable and Non-Stable CoCrMo Wear and Corrosion Debris Generated In-Situ for Total Hip Replacement.

Metal wear and corrosion debris remain a limiting factor for long-term durability of total hip replacement (THR). Common wear particle production techniques for research differ from the actual tribocorrosion processes at the implant site, potentially causing loss of valuable information. The aim of this study was to investigate reactions to freshly generated and time-stabilized particles and ions released from CoCrMo-alloy using a bio-tribometer, which mimics conditions of the periprosthetic environment. THP-1 macrophages were challenged with freshly produced or time-stabilized wear debris. Wear generation took place in a custom-built bio-tribometer inside a CO2 incubator operating with a reciprocating rotation of an Al2O3 ball against a CoCrMo disc. Two different electrochemical conditions with increasingly forced corrosion rates were tested: +0.45 V (passive domain) and +0.67 V (transition to transpassive domain). Cell viability, proinflammatory cytokines, electrochemical measurements and ICP-MS metal ion content analyses were performed. Cobalt/ chromium concentrations were 6.6/ 1.6 ppm in the passive domain and almost doubled to 11.4/ 3.0 ppm in the passive-transpassive domain. Under those electrochemical conditions, freshly produced and time-stabilized CoCrMo wear decreased cell viability to the same extent. Secretion of proinflammatory cytokines were not significantly different for freshly produced and time-stabilized debris. This study suggests that freshly generated and time-stabilized metal particles/ions cause similar toxicity and inflammatory reactions in macrophages, indicating that standard practices for generating wear debris are valid methods to evaluate wear particle disease. Other cell types, materials, and corrosion potentials need to be studied in the future to solidify the conclusion.

Electrophoretic deposition of gentamicin and chitosan into titanium nanotubes to target periprosthetic joint infection.

Periprosthetic joint infection (PJI) occurs in 1%-2% of primary total hip and knee arthroplasties; the rate can reach 20% in individuals at risk. Due to the low local bioavailability of systemic antibiotics and possible off-target effects, localized drug delivery systems are of great importance. Our aim was the electrophoretic deposition (EPD) of gentamicin and chitosan in Titanium (Ti) nanotubes to establish a local, prolonged antibiotic delivery. Nanotubes were created on Ti wire with a two-step anodization process. For drug deposition, EPD and the air-dry methods were compared. For a prolonged drug release, gentamicin and crosslinked chitosan were deposited in a two-step EPD process. Drug release was quantified by fractional volume sampling. The Ti wires were tested against Staphylococcus aureus by agar dilution and liquid culture methods. MC3T3-E1 osteoblastic cell viability was determined with trypan blue. Nanotubes were characterized by a 100 nm diameter and 7 µm length. EPD allowed a higher amount of gentamicin deposited than the air-dry method. Drug deposition was controllable by adjusting the voltage and duration of the EPD process. The crosslinked chitosan layer allowed diffusion-driven release kinetics for up to 3 days. Gentamicin-loaded Ti wires significantly inhibited bacterial growth and resulted in a larger inhibition zone compared to unloaded wires. Twenty-four hours of incubation with loaded wires did not have a significant effect on osteoblast viability. Gentamicin-loaded Ti nanotubes represent a promising approach for PJI prevention, as well as a valuable preclinical tool for the investigation of localized drug delivery systems created on Ti surface.

Advances in pharmacotherapy for ulcerative colitis: a focus on JAK1 inhibitors.

INTRODUCTION: Janus kinase (JAK) inhibitors are an emerging class of small-molecule drugs, providing targeted therapy for a variety of diseases, and have made their way into the treatment of armamentarium of ulcerative colitis (UC) in recent years. AREAS COVERED: This review focuses on the pharmacokinetics, safety, and efficacy of selective JAK1 inhibitors in the treatment of moderate-to-severe UC. The PubMed database and clinicaltrials.gov were consulted using keywords - further expanded in the methods section. The search was focused on full-text publications in English. No publication date restrictions were imposed. EXPERT OPINION: JAK1 inhibitors are small-molecule drugs used in the treatment of ulcerative colitis and other immune mediated inflammatory diseases. They are orally bioavailable and have a rapid mechanism of action and no immunogenicity. JAK inhibitors can be used for the management of both naïve patients and biological-experienced patients.Particular attention should be paid to elderly patients or those with cardiovascular or oncological risk factors, in whom JAK inhibitors should be recommended only if no alternatives are available. In addition, JAK inhibitors have the potential to be combined with other biological drugs or small molecules for the management of difficult-to-treat cases.

Noninvasive Assessment of Postoperative Disease Recurrence in Crohn's Disease: A Multicenter, Prospective Cohort Study on Behalf of the Italian Group for Inflammatory Bowel Disease.

BACKGROUND & AIMS: Colonoscopy (CS) is the gold standard to assess postoperative recurrence (POR) in Crohn's disease (CD). However, CS is invasive and may be poorly tolerated by patients. The aim of this study was to prospectively assess the diagnostic accuracy of a noninvasive approach in detecting POR, using the endoscopic Rutgeerts' score (RS) as the reference standard. METHODS: Consecutive patients with CD who underwent ileo-cecal resection were prospectively enrolled in 3 referral Italian centers. Patients underwent CS and bowel ultrasound within 1 year of surgery. Uni- and multivariable analyses were used to assess the correlation between noninvasive parameters and endoscopic recurrence, defined by a RS ≥2. RESULTS: Ninety-one patients were enrolled. Sixty patients (66%) experienced endoscopic POR. The multivariable analysis identified bowel wall thickness (BWT) per 1-mm increase (odds ratio [OR], 2.43; 95% confidence interval [CI], 1.21-4.89; P = .012), the presence of mesenteric lymph nodes (OR, 15.63; 95% CI, 1.48-164.54; P = .022), and fecal calprotectin (FC) values ≥50 mcg/g (OR, 8.58; 95% CI, 2.45-29.99; P < .001) as independent predictors for endoscopic recurrence. The presence of lymph nodes or the combination of BWT ≥3 mm and FC values ≥50 mcg/g correctly classified 56% and 75% of patients, with less than 5% of patients falsely classified as having endoscopic recurrence. Conversely, the combination of BWT <3 mm and FC <50 mcg/g correctly classified 74% of patients with only 4.5% of patients falsely classified as not having endoscopic recurrence. CONCLUSIONS: A noninvasive approach combining bowel ultrasound and FC can be used with confidence for detecting POR in patients with CD without the requirement for CS.

The Role of IL-23 Inhibitors in Crohn's Disease.

Promoting a Th17 pathogenic response, the interleukin (IL)-23 pathway is crucial in the pathophysiology of inflammatory bowel disease (IBD). With a favorable safety profile, ustekinumab, a monoclonal antibody targeting the shared p40 component of IL-12/23, is currently approved for the treatment of IBD in patients with disease refractory to corticosteroids and biologic drugs. Risankizumab, mirikizumab, and guselkumab are specific IL-23p19 antagonists tested for the treatment of Crohn's disease (CD). However, only risankizumab currently has been approved for its treatment. Trials with guselkumab and mirikizumab are currently ongoing, with promising preliminary efficacy and safety results. In this review, we provide a summary of the current knowledge about selective IL-23 inhibitors, focusing on their positioning in the therapeutic algorithm of patients with moderate to severe CD.

Microstructure and electrochemical behavior of contemporary Ti6Al4V implant alloys.

Ti6Al4V is the most common titanium alloy within the biomaterial field. While material standards for different variations of this alloy exist, there are only minimal requirements with respect to its microstructure which is directly related to the alloy's properties. Thus, a better understanding of the Ti6Al4V microstructure of common contemporary implant components and its effect on the electrochemical behavior is needed; including additively manufactured (AM) devices. Therefore, this study aimed at characterizing the microstructures of conventional and AM total joint replacement components, and to identify the effect of microstructure on the electrochemical behavior. Thus, 22 components from conventional (surgically retrieved cast and wrought implants) and AM implants (not previously implanted) were analysed to characterize microstructure by means of electron backscatter diffraction (EBSD) and energy dispersive X-Ray spectroscopy (EDS), and tested to determine its electrochemical behavior (potentiodynamic polarization and EIS). The microstructure of the conventional implants varied broadly but could be categorized into four groups as to their grain size and shape: fine equiaxed, coarse equiaxed, bimodal, and lamellar. The AM components exhibited a fifth category: lath-type. The AM components had a network of ß-phase along the α-phase grain boundaries, prior ß-grains, and manufacturing voids. Finally, the electrochemical study showed that the equiaxed coarse grains and lath-type grains (AM components) had inferior electrochemical behavior, whereas cast alloys had superior electrochemical behaviour; fine-grained wrought alloys likely provide the best compromise between electrochemical and mechanical properties.

Alloys Used in Different Temporomandibular Joint Reconstruction Replacement Prostheses Exhibit Variable Microstructures and Electrochemical Properties.

PURPOSE: Metallic temporomandibular joint replacement (TMJR) systems vary depending on design, material composition, and manufacturing methods such as casting, forging, and additive manufacturing. Therefore, the purpose of this study was to measure the association between manufacturing process of TMJR systems in terms of microstructure and electrochemical properties. MATERIALS AND METHODS: The sample was composed of new or surgically retrieved TMJ replacement devices of either titanium alloy (Ti6Al4V) or cobalt-chromium-molybdenum (CoCrMo) alloy from 8 different manufacturers. The primary predictor variable was alloy type, according to its manufacturing process (wrought, cast, additively manufactured [AM]). The primary outcome variables were 1) microstructure (grain size, aspect ratio, and phase content) and 2) corrosion potential and current, polarization resistance, and capacitance. Differences between alloy groups were determined by t tests, Kruskal-Wallis, and Mann-Whitney tests. RESULTS: We demonstrated that the TMJR CoCrMo and Ti6Al4V alloy microstructures can vary broadly within American Society for Testing and Materials specifications, where the components made of Ti6Al4V had 3 types of microstructures (equiaxial, bimodal, and martensitic) out of 10 samples, and the components made of CoCrMo had 2 types of microstructure (equiaxial and dendritic) out of 16 samples. Some CoCrMo alloys exhibited preferential corrosion sites, while wrought Ti6Al4V alloys trended toward a superior corrosion behavior (corrosion rate: 2 × 10-9 A/cm2, polarization resistance: 5,000,000 kΩcm2, and capacitance: 10 µSsa/cm2) compared with AM alloys (39 × 10-9 A/cm2, 1676 kΩcm2, 36 µSsa/cm2, respectively), where 4 samples of each group were tested and repeated 5 times. Among four AM devices, two exhibited a significantly inferior corrosion behavior. CONCLUSIONS: Although AM is an exciting emerging new technology that allows manufacturing of custom-made TMJR, their corrosion behavior is still inferior in comparison to that of traditional wrought alloys. Preventing corrosion is crucial because it can cause surface defects that may lead to implant fracture.

Biotribometer for Assessment of Cell and Tissue Toxicity of Orthopedic Metal Implant Debris.

A novel approach to address the clinical issue of cell response to wear and corrosion debris from metal orthopedic implants consists of combining cell culturing with wear and corrosion debris generation. A biotribometer equipped with a three-electrode electrochemical chamber operates inside a CO2 incubator. Cells are cultured at the bottom of the chamber. A ceramic ball (hip implant head) is pressed against a metal disc under a constant load, and set in reciprocating rotation. An anodic electrochemical potential can be applied to a metal disc for accelerated corrosion conditions, or the free potential may be monitored.Measurements of gravimetric and volumetric material loss of the metal disc postwear provide quantitative information that can be put in relation to biological assays (e.g., cell viability and secretion of proinflammatory cytokines). This approach allows for the comparison of candidate metals potentially undergoing tribocorrosion in clinical use. The approach allows to identify the effect of any metastable debris, likely active in vivo.

Nickel-free high-nitrogen austenitic steel outperforms CoCrMo alloy regarding tribocorrosion in simulated inflammatory synovial fluids.

CoCrMo alloys are well-established biomaterials used for orthopedic joint replacement implants. However, such alloys have been associated with clinical problems related to wear and corrosion. A new generation of austenitic high-nitrogen steels (AHNSs) has been developed for biomedical applications. Here, we have addressed influences of hyaluronic acid, combined with inflammatory (oxidizing) conditions, on tribocorrosion of the high-nitrogen FeCrMnMoN0.9 steel (DIN/EN X13CrMnMoN18-14-3, 1.4452), and of the low carbon CoCrMo0.03 alloy (ISO 5832-12). We aimed to elucidate critical and clinically relevant conditions affecting the implant's performance in certain orthopedic applications. Tribocorrosion tests were conducted in triplicate, with discs under reciprocating sliding wear against a ceramic ball. Different lubricants were prepared from standardized bovine serum solution (ISO 14242-1), with variable additions of hyaluronic acid (HA) and hydrogen peroxide (H2 O2 ). Test conditions were: 37°C, 86,400 cycles, 37 N load (20-40 MPa after run-in phase). Volumetric wear was quantified; surfaces were evaluated by electrochemical parameters and microscopy/spectroscopy analyses (SEM/EDS). Factorial analysis of variance tests was conducted to examine the effects of HA, H2 O2 , and test material on wear- and corrosion-related dependent variables. Tribocorrosion performances of CoCrMo0.03 and FeCrMnMoN0.9 were comparable in fluids without H2 O2 . With higher H2 O2 concentrations, tribocorrosion increased for CoCrMo0.03 , while this was not the case for FeCrMnMoN0.9 . HA significantly enhanced wear of CoCrMo0.03 in the absence of H2 O2 , while it mitigated the tribocorrosive action of 3 mM H2 O2 ; HA had no impact on FeCrMnMoN0.9 . These results indicate a favorable performance of FeCrMnMoN0.9 compared to CoCrMo0.03 , and encourage further research on AHNS for certain orthopedic applications.

Rediscovering histology: what is new in endoscopy for inflammatory bowel disease?

The potential of endoscopic evaluation in the management of inflammatory bowel diseases (IBD) has undoubtedly grown over the last few years. When dealing with IBD patients, histological remission (HR) is now considered a desirable target along with symptomatic and endoscopic remission, due to its association with better long-term outcomes. Consequently, the ability of endoscopic techniques to reflect microscopic findings in vivo without having to collect biopsies has become of upmost importance. In this context, a more accurate evaluation of inflammatory disease activity and the detection of dysplasia represent two mainstay targets for IBD endoscopists. New diagnostic technologies have been developed, such as dye-less chromoendoscopy, endomicroscopy, and molecular imaging, but their real incorporation in daily practice is not yet well defined. Although dye-chromoendoscopy is still recommended as the gold standard approach in dysplasia surveillance, recent research questioned the superiority of this technique over new advanced dye-less modalities [narrow band imaging (NBI), Fuji intelligent color enhancement (FICE), i-scan, blue light imaging (BLI) and linked color imaging (LCI)]. The endoscopic armamentarium might also be enriched by new video capsule endoscopy for monitoring disease activity, and high expectations are placed on the application of artificial intelligence (AI) systems to reduce operator-subjectivity and inter-observer variability. The goal of this review is to provide an updated insight on contemporary knowledge regarding new endoscopic techniques and devices, with special focus on their role in the assessment of disease activity and colorectal cancer surveillance.

Nursing-sensitive outcomes in adult inflammatory bowel disease: A systematic review.

AIMS: To evaluate nursing activity through outcomes that are affected, provided, and/or influenced by nurses and defined as nursing-sensitive outcomes in adult IBD patients. DESIGN: Systematic review without meta-analysis. DATA SOURCES: PubMed, Embase, CINAHL, PsycINFO, and the Cochrane Library databases on August 2019. REVIEW METHODS: Peer-reviewed articles published between 2000-2020 were reviewed. The outcome measures were contextualized and presented by OMERACT Filter 2.0. RESULTS: Twenty-four studies were included. Eighteen nursing-sensitive outcomes were identified. These outcomes defined eight domains for health intervention, fitting into three core areas (resource use/economic impact, life impact, pathophysiological manifestations). Fifty-three measurement instruments were identified. CONCLUSIONS: Through 53 measurement tools, with use of OMERACT framework, 18 nursing-sensitive outcomes in the main 3 core areas were identified, highlighting the multidimensional role of nursing. Further insights are to be carried out to define nursing outcomes included in IBD nursing intervention studies. IMPACT: These results could serve as a cornerstone for further investigations and validation by a panel of experts to standardizing nursing activity in a multidisciplinary context.

Corrosion resistance of the nickel-free high-nitrogen steel FeCrMnMoN0.9 under simulated inflammatory conditions.

Nickel-free, high-nitrogen austenitic steels (AHNS) have been introduced for biomedical applications, with encouraging results in terms of mechanical and corrosion properties. Here, we tested the corrosion resistance of a nickel-free high nitrogen steel (FeCrMnMoN0.9) in bovine serum solutions containing 0 or 3 g/L hyaluronic acid (HA), and 0, 3, or 30 mM hydrogen peroxide (H2 O2 ) simulating no, moderate, or strong inflammatory conditions, respectively. Nondestructive electrochemical measurements (open circuit potential [OCP], linear polarization resistance "RP ", and electrochemical impedance spectroscopy) were run in triplicate over 10 hr. The presence of HA had no significant effect either on the stabilized OCP values, or on the corrosion resistance of FeCrMnMoN0.9. Increasing H2 O2 concentrations shifted the OCP to more electropositive values; the corrosion resistance decreased only at a 30 mM H2 O2 . Final RP values at 0, 3, and 30 mM H2 O2 resulted in 1598 ± 276, 1746 ± 308, and 439 ± 47 kΩ cm2 , respectively. These values were 4-14 times higher, than the RP values measured on LC-CoCrMo in our previous study, conducted under identical conditions. While these findings are encouraging, future studies need to focus on tribocorrosive properties of the AHNS to evaluate its applicability in joint replacement.

New Paradigms to Help Decisions in Treatment Choice: Head to Head Trial of Biological Therapies in Inflammatory Bowel Diseases.

The increasing armamentarium of drugs for inflammatory bowel disease (IBD) requires a direct comparison of different therapeutic options in order to guide physicians in the choice of the most appropriate treatment for their patients. Head-to-head trials, considered the gold standard in comparative research in IBD, allow to compare different therapies in the same population and setting, but also to evaluate different treatment strategies. Although head-to-head trials including biologics and immunosuppressive therapy in IBD have been performed decades ago, the interest in these direct comparisons is growing since the publication of the first randomized controlled trial directly comparing biologic agents with different molecular targets. This review provides an overview of the past and current IBD head-to-head trials, considering their respective strengths and limitations in a real-life setting.

Absence of COVID-19 Infection in Patients Accessing IBD Unit at Humanitas, Milan: Implications for Postlockdown Measures.

INTRODUCTION: The risk of coronavirus disease-19 infection for healthcare professionals and patients in hospitals remains unclear. METHODS: We investigated whether precautions adopted in our inflammatory bowel disease (IBD) unit have minimized the risks of infection for all patients accessing our facilities in a 1-month period by assessing the rate of coronavirus disease-19 infection in the follow-up period. RESULTS: Three hundred-twenty patients with IBD were included. None were infected from severe acute respiratory syndrome-coronavirus 2 in the follow-up period. None of the IBD team members were infected. DISCUSSION: Neither pharmacological immunosuppression nor access to the hospital seem to be risk factors for infection in patients with IBD.

SFED recommendations for IBD endoscopy during COVID-19 pandemic: Italian and French experience.

The current coronavirus disease 2019 (COVID-19) pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection has required a complete change in the management of patients with inflammatory bowel disease (IBD) who need to undergo endoscopic procedures. Several preventive measures must be taken to avoid the spread of infection among health-care professionals and patients with IBD, including the use of personal protective equipment, greater attention to endoscopic room hygiene and rescheduling of non-urgent procedures. This Perspective aims to provide a guide based on the Italian and French experience to better face the difficulties encountered by endoscopists during this global health emergency. In particular, recommendations regarding the use of personal protective equipment to prevent COVID-19 transmission, both for patients and health-care professionals, are proposed and different scenarios in endoscopic IBD management are evaluated to suggest when endoscopy could be rescheduled and replaced by alternative biomarkers.

Incidence and Patterns of COVID-19 Among Inflammatory Bowel Disease Patients From the Nancy and Milan Cohorts.

The first cases of COVID-19 infection were reported in December, 2019, in Wuhan, China. Italy (in particular Lombardy) and France (in particular Northeast) have been gravely hit. Both physicians and inflammatory bowel disease (IBD) patients are deeply concerned that immunosuppressants or biologics may increase the risk of COVID-19 infection. IOIBD has put in place an international registry, SECURE-IBD, for tracking all the cases with IBDs infected by COVID-19 (SECURE-IBD registry: http://www.covidibd.org). It will describe the outcomes of infected patients and the association between IBD-related medications and these outcomes.

Maintaining the Quality Standards of Care for Inflammatory Bowel Disease Patients During the COVID-19 Pandemic.

Since February 20, 2020, the SARS-COV2 infection has spread in Lombardy, and in the rest of the Italian regions, forcing our government to impose a national lockdown.1 Hospitals have been forced to adapt and to restructure their units to cope with this urgent new critical situation.2 Alternative solutions have been found to manage patients with inflammatory bowel disease (IBD), including remote monitoring, drug home delivery, limitations for infusion units, and patient education on measures to prevent infection,3 to maintain high-quality care.4.