Role of ustekinumab in treatment of ulcerative colitis: a narrative review.

The therapeutic armamentarium for gastroenterologists in treating ulcerative colitis (UC) has been rapidly growing since the introduction of monoclonal antibodies directed against anti-TNFs. Ustekinumab is a monoclonal antibody binding the shared p40 subunit of IL-12 and IL-23, and the inhibition of these two cytokines, implicated in host response to microbial pathogens, has demonstrated clinical efficacy in different immune-mediated diseases, including moderate-to-severe UC. This narrative review summarizes the newest clinical evidence regarding the efficacy, effectiveness and safety of ustekinumab in moderate-to-severe UC, including specific situations (pregnancy, breastfeeding, elderly/pediatric populations, extraintestinal manifestations, acute severe UC, pouchitis and dual biological therapy).

Safety and effectiveness of tofacitinib in ulcerative colitis: Data from TOFA-UC, a SN-IBD study.

Background: Real-world evidence is needed to determine the value of tofacitinib (TOFA) for the treatment of ulcerative colitis (UC).

Aim: To assess the safety and effectiveness of TOFA in clinical practice.

Methods: TOFA-UC is a multicenter, observational study performed among the Sicilian Network for Inflammatory Bowel Disease (SN-IBD).

Ustekinumab is a promising option for the treatment of postoperative recurrence of Crohn's disease.

Background And Aim: Postoperative recurrence (POR) following ileocolonic resection is a major concern in patients with Crohn's disease (CD). The role of ustekinumab (UST) in this setting is poorly known.

Methods: All consecutive CD patients with a baseline colonoscopy at 6-12 months from ileocolonic resection showing POR (Rutgeerts score ≥ i2) who were treated with UST after the baseline colonoscopy and with an available post-treatment endoscopy, were extracted from the cohort of the Sicilian Network for Inflammatory Bowel Diseases (SN-IBD).

Sarcopenia is a negative predictive factor for endoscopic remission in patients with Crohn's disease treated with biologics.

Background: Sarcopenia has been associated with poor prognosis in chronic diseases.

Aims: To investigate the role of sarcopenia in predicting clinical and endoscopic outcomes in patients with Crohn's disease (CD).

Methods: Consecutive CD patients who started biologics between 2014 and 2020 and underwent abdominal magnetic resonance or computed tomography within 6 months from the beginning of the biological therapy were enroled.

The effectiveness of ustekinumab and vedolizumab as third-line biologic therapy in patients with Crohn's disease.

Background: The effectiveness of Ustekinumab (UST) and Vedolizumab (VDZ) in patients with Crohn's disease (CD) as third-line biologic therapies is unclear.

Aims: We performed a multicentre, real-world assessment of the effectiveness of UST and VDZ among highly-refractory patients with CD.

Methods: Data of consecutive patients with CD treated with UST and VDZ as third-line biologic therapy until December 2021 were extracted from the cohort of the Sicilian Network for Inflammatory Bowel Disease (SN-IBD).

Spondyloarthropathy in Inflammatory Bowel Disease: From Pathophysiology to Pharmacological Targets.

Spondyloarthritis (SpA) represents one of the most frequent extraintestinal manifestations of inflammatory bowel disease (IBD). Evidence of shared genetic and molecular pathways underlying both diseases is emerging, which has led to rational approaches when treating patients with concomitant diseases. Clinical efficacy of tumor necrosis factor (TNF) antagonists has been ascertained over the years, and they currently represent the cornerstone of treatment in patients with IBD and SpA, but the therapeutic armamentarium in these cases has been recently expanded.

Severe Activity of Inflammatory Bowel Disease is a Risk Factor for Severe COVID-19.

Background: Data from the first wave of the coronavirus disease 2019 (COVID-19) pandemic suggested that patients with inflammatory bowel disease (IBD) are not at higher risk of being infected by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) than the general population and that a worse prognosis is not associated with immunomodulatory drugs, with the possible exception of systemic steroids.

Methods: This retrospective, observational study included consecutive IBD patients from the Sicilian Network for Inflammatory Bowel Disease (SN-IBD) cohort who had a SARS-CoV-2 infection diagnosis (polymerase chain reaction-confirmed presence of the viral genome in a nasopharyngeal swab) during the second COVID-19 pandemic wave (September 2020 to December 2020). Data regarding demographics, IBD features and treatments, and comorbidities were analyzed in correlation with COVID-19 clinical outcomes.

Effectiveness and safety of an on-demand ferric carboxymaltose infusion strategy in patients with inflammatory bowel disease: a real world experience.

Background: We evaluated an on-demand ferric carboxymaltose (FCM) infusion strategy in inflammatory bowel disease (IBD) patients with iron deficiency anemia (IDA).

Aims: The primary outcome was the response rate to single or multiple FCM infusions after 12 months. Secondary outcomes were the response rate to a single FCM infusion after 3 months and the FCM safety profile.

Vedolizumab may be an effective option for the treatment of postoperative recurrence of Crohn's disease.

Background: The role of Vedolizumab (VDZ) as therapeutic option for the postoperative recurrence of Crohn's disease (CD) following ileocolonic resection is unknown.

Aims: To assess the effectiveness of VDZ in this setting.

Methods: All consecutive CD patients with a baseline colonoscopy at 6-12 months from the ileocolonic resection showing postoperative recurrence (Rutgeerts score ≥i2) and treated with VDZ after the baseline colonoscopy were extracted from the cohort of the Sicilian Network for Inflammatory Bowel Diseases (SN-IBD).

Blood-based prognostic biomarkers in Crohn's Disease patients on biologics: a promising tool to predict endoscopic outcomes.

Objective: There is a growing need for biomarkers to predict therapeutic outcome in Crohn's disease (CD).

Main Outcome Measures: The aim was to evaluate whether NLR (neutrophil-to-lymphocyte ratio), PLR (platelet-to-lymphocyte ratio), ELR (eosinophil-to-lymphocyte ratio), and ENLR (eosinophil*neutrophil-to-lymphocyte ratio), could be prognostic biomarkers of endoscopic response (ER) when starting biologics.

Research Design And Methods: Patients with CD who started biologics were enrolled.

Effectiveness of Ustekinumab on Crohn's Disease Associated Spondyloarthropathy: Real-World Data from the Sicilian Network for Inflammatory Bowel Diseases (SN-IBD).

Background: The effectiveness of Ustekinumab (UST) on Crohn's disease (CD)-associated spondyloarthropathy (SpA) is currently unknown.

Research Design And Methods: All consecutive CD patients with active SpA at the initiation of the treatment with UST were extracted from the cohort of the Sicilian Network for Inflammatory Bowel Diseases (SN-IBD). The primary outcome was the articular response at 8 and 24 weeks, defined as the disappearance of objective signs of arthritis (swelling and/or articular stiffness) and resolution of pain.

Proteomic Screening and Lasso Regression Reveal Differential Signaling in Insulin and Insulin-like Growth Factor I (IGF1) Pathways.

Insulin and insulin-like growth factor I (IGF1) influence cancer risk and progression through poorly understood mechanisms. To better understand the roles of insulin and IGF1 signaling in breast cancer, we combined proteomic screening with computational network inference to uncover differences in IGF1 and insulin induced signaling. Using reverse phase protein array, we measured the levels of 134 proteins in 21 breast cancer cell lines stimulated with IGF1 or insulin for up to 48 h.

The estrogen receptor alpha nuclear localization sequence is critical for fulvestrant-induced degradation of the receptor.

Fulvestrant, a selective estrogen receptor down-regulator (SERD) is a pure competitive antagonist of estrogen receptor alpha (ERα). Fulvestrant binds ERα and reduces the receptor's half-life by increasing protein turnover, however, its mechanism of action is not fully understood. In this study, we show that removal of the ERα nuclear localization sequence (ERΔNLS) resulted in a predominantly cytoplasmic ERα that was degraded in response to 17-β-estradiol (E2) but was resistant to degradation by fulvestrant.

Forkhead box A1 (FOXA1) is a key mediator of insulin-like growth factor I (IGF-I) activity.

The insulin-like growth factor receptor (IGF-IR) has been implicated in a number of human tumors, including breast cancer. Data from human breast tumors has demonstrated that IGF-IR is over-expressed and hyper-phosphorylated. Additionally, microarray analysis has shown that IGF-I treatment of MCF7 cells leads to a gene signature comprised of induced and repressed genes, which correlated with luminal B tumors.

Estrogen and insulin-like growth factor-I (IGF-I) independently down-regulate critical repressors of breast cancer growth.

Although estrogen receptor alpha (ERα) and insulin-like growth factor (IGF) signaling are important for normal mammary development and breast cancer, cross-talk between these pathways, particularly at the level of transcription, remains poorly understood. We performed microarray analysis on MCF-7 breast cancer cells treated with estradiol (E2) or IGF-I for 3 or 24 h. IGF-I regulated mRNA of five to tenfold more genes than E2, and many genes were co-regulated by both ligands.

Beclomethasone dipropionate in Crohn's ileitis: a randomised, double-blind trial.

Background: Steroids, the mainstay of Crohn's disease treatment, have been associated with systemic side effects.

Aim: To evaluate the efficacy and tolerability of beclomethasone dipropionate for maintaining remission induced by a short course of systemic steroids in patients with Crohn's ileitis with or without right colonic involvement.

Methods: Patients (n=84) with active Crohn's disease who achieved remission during a 2-week prednisone run-in period were randomised to receive beclomethasone dipropionate for 24 weeks or continue prednisone for a further 2 weeks followed by placebo for 22 weeks.

Proteomic and transcriptomic profiling reveals a link between the PI3K pathway and lower estrogen-receptor (ER) levels and activity in ER+ breast cancer.

Introduction: Accumulating evidence suggests that both levels and activity of the estrogen receptor (ER) and the progesterone receptor (PR) are dramatically influenced by growth-factor receptor (GFR) signaling pathways, and that this crosstalk is a major determinant of both breast cancer progression and response to therapy. The phosphatidylinositol 3-kinase (PI3K) pathway, a key mediator of GFR signaling, is one of the most altered pathways in breast cancer. We thus examined whether deregulated PI3K signaling in luminal ER+ breast tumors is associated with ER level and activity and intrinsic molecular subtype.

Insulin-like growth factor-I activates gene transcription programs strongly associated with poor breast cancer prognosis.

Purpose: Substantial evidence implicates insulin-like growth factor-I (IGF-I) signaling in the development and progression of breast cancer. To more clearly elucidate the role of IGF in human breast cancer, we identified and then examined gene expression patterns of IGF-I-treated breast cancer cells.

Methods: MCF-7 cells were stimulated with IGF-I for 3 or 24 hours and were profiled for greater than 22,000 RNA transcripts.

The type I insulin-like growth factor receptor pathway: a key player in cancer therapeutic resistance.

The insulin-like growth factor (IGF) ligands stimulate cellular proliferation and survival by activating the type I insulin-like growth factor receptor (IGF-IR). As a result, the IGF signaling system is implicated in a number of cancers, including those of the breast, prostate, and lung. In addition to mitogenic and anti-apoptotic roles that may directly influence tumor development, IGF-IR also appears to be a critical determinant of response to numerous cancer therapies.

Familial occurrence of inflammatory bowel disease in celiac disease.

Background: The authors have previously reported a possible increased risk of the familial occurrence of Crohn's disease in patients with celiac disease.

Aim: The aim of the current study was to evaluate in a case-control study the familial occurrence of inflammatory bowel disease (IBD) in first-degree relatives of patients with celiac disease.

Methods: One hundred eleven consecutive patients with biopsy-proven celiac disease were interviewed to ascertain whether IBD was present in first-degree relatives.