Background: Breast cancer is an important cause of cancerrelated death in women. In this pathological condition, arginase plays a role by providing ornithine as a substrate for the biosynthesis of polyamines which are important in tumor progression. The aim of this work was to determine the arginase activity in the plasma and tumors of patients with breast cancer; also, we investigated the relationship between this activity and the presence of the estrogen receptor. Patients and Methods: We evaluated the plasma arginase activity levels in 80 women with breast cancer and 42 healthy control subjects. We also measured the arginase levels in 42 breast cancer biopsies and 42 control tissues. Results: The mean activity of arginase in plasma was higher in breast cancer patients (0.78 nM/min/mg protein ± 0.04; p = 0.001) than in healthy volunteers (0.53 nM/ min/mg protein ± 0.04); however, this difference was indicative of patients in the advanced stages of the disease (n = 38, stage III; p < 0.0001). In addition, we did not find a relationship between the estrogen receptor and arginase activity. Conclusion: Our results show a higher arginase activity in the plasma of patients in the advanced stages of the disease, suggesting that arginase activity could serve as a possible biological marker of breast cancer progression.

Background Current therapeutic goals in Crohn’s disease (CD) include not only the mere absence of symptoms but also the objective resolution of macroscopic lesions, so-called deep remission (DR), which has been related to better outcomes. DR is usually acknowledged by endoscopy, although magnetic resonance (MR) or intestinal ultrasound (IUS) are also reliable, provide extramucosal information and may be more appropriate in certain clinical scenarios. Data regarding the achievement of DR with ustekinumab in real-life clinical practice is still scarce. Methods Retrospective cohort study carried out in a tertiary hospital between April 2017 and April 2019 including patients who had clinically active CD (Harvey–Bradshaw index [HBI] ≥ 4) objectively assessed by either endoscopy, MR or IUS; received intravenous induction with ustekinumab, had achieved clinical remission and had treatment response assessed by either endoscopy, MR or IUS. DR was defined by SES-CD 0–3 or Rutgeerts index i0 if endoscopically assessed, or by complete normalisation of inflammatory parameters on cross-sectional imaging. Endoscopic response was defined by the decrease of SES-CD of 50% compared with baseline. Radiographic response was defined by improvement in bowel wall thickness, inflammatory fat, mural blood flow and hyperenhancement compared with baseline imaging by physician global assessment. Demographics, clinical data and information regarding ustekinumab treatment were collected. Results 90 patients treated with ustekinumab at our centre were analyzed, but only 28 met inclusion criteria (14(50%) female; median age 45 (43–50)) with a median follow-up of 19 (IQR: 15–23) months. All of them had previously failed to antiTNFα and 20 (71%) failed to ≥2 biologics. Treatment response assessment was made by endoscopy (22 cases; 79%) or cross-sectional imaging technique (6 cases; 21%) in a median time of 10 months (IQR: 7–13) from the start of treatment. Deep remission was achieved in 18 (64%) patients. Endoscopic response was achieved in 5 (18%) additional patients. Five (18%) remaining patients obtained no objective response to ustekinumab despite being in clinical remission. Patients who had received prior treatment with ≥2 biologics or those classified as B2 or B3 according to Montreal Classification were less likely to achieve deep remission, although those associations did not reach statistical significance. Conclusion In our experience, a majority of refractory CD patients who achieved clinical remission with ustekinumab also reached deep remission assessed by either endoscopy, MR or IUS.

Background Current therapeutic goals in inflammatory bowel disease (IBD) include not only the mere absence of symptoms but also the resolution of endoscopic lesions, so-called mucosal healing (MH), which has been related to better outcomes. Data regarding the achievement of MH with vedolizumab (VDZ) in real-life clinical practice is still scarce. Methods Retrospective cohort study was carried out in a tertiary hospital between January 2015 and April 2019 including patients with a basal colonoscopy showing activity and who achieved clinical remission under treatment with VDZ, defined by partial Mayo score &lt;2 for ulcerative colitis (UC) and Harvey–Bradshaw Index score (HBI) &lt;4 for Crohn’s disease (CD). Surveillance colonoscopy was performed along with the follow-up according to clinical practice. In UC patients, MH was defined as Mayo Endoscopic Subscore (MES) = 0; the endoscopic response was defined by a decrease in MES ≥1 point. In CD, MH was defined by achievement SES-CD = 0–3 or Rutgeerts index i0; the endoscopic response was defined by a decrease of SES-CD of 50% or Rutgeerts index &lt;i2 with at least 1 point of decease compared with baseline. Results In total, 118 patients treated with VDZ were analysed, but only 45 met inclusion criteria with a median follow-up of 21 (IQR: 14–19) months. Surveillance colonoscopy was performed after a median time of 12 months (IQR:9–17) of treatment. MH achieved in 33/45 patients (73%): 17/23 CD patients (74%) and 16/22 UC patients (73%). The endoscopic response was achieved in 9 of the remaining 12 patients: 3/6 CD patients and 6/6 UC patients. Only 3 (7%) of patients included showed no endoscopic benefit at the time of surveillance endoscopy. In multivariate analysis, probability of not achieving MH was 75% in patients previously treated with immunosuppressants (ISS) (HR 0.25, 0.11–0.55 IC95; p = 0.001) and 60% in patients previously treated with anti-TNFα (HR 0.40, 0.18–0.90 95% CI; p = 0.026). Type of IBD, concomitant ISS, corticosteroid use at induction, baseline endoscopy score or duration of disease before VDZ treatment were not associated with the achievement of MH. Conclusion In our experience, most of the patients who achieve clinical remission with VDZ also achieve MH. Refractory patients were less likely to achieve MH despite having achieved clinical remission.

Background Loss of response to anti-TNF drugs in patients with inflammatory bowel disease (IBD) is frequent and, in case of low drug levels, treatment intensification is recommended. In addition, in cases in which clinical response without attainment of remission (clinical, endoscopic or radiological), intensification could be justified since higher drug levels are associated with better outcomes. For adalimumab (ADA), the standard intensification regimen is 40mg every week (ew). Availability of ADA 80mg pre-filled pens has enabled every other week (eow) intensification. We assessed the clinical efficacy of intensification with ADA 80mg eow. Methods This retrospective study was conducted at a tertiary hospital in Spain. Patients with IBD receiving maintenance ADA 80mg eow with clinical, biomarker and drug level assessments were included. Demographics and clinical, biological and endoscopic evaluation of the disease before and after ADA intensification, and pharmacokinetic assessments, were collected. Results 87 patients (72 Crohn’s disease, 15 ulcerative colitis; average age 50 years) were included. Reasons for ADA intensification were: low ADA levels - &lt;5 µg/mL - (17%), low ADA levels - &lt;5 µg/mL- without clinical response (63%), clinical response without clinical remission (15%) and active disease on objective evaluation (including colonoscopy, MRI, capsule endoscopy and/or intestinal ultrasound; 5%). Following treatment intensification to ADA 80mg eow, 75 patients (86%) were in clinical remission and 69 (79.3%) were in biologic remission (clinical remission and normalisation of biomarkers). After a median follow-up of 19 months (IQR 13–25), 63 patients (72%) remained on treatment and in clinical remission. There were no serious infections, hospitalisations or deaths. Drug costs did not increase with the 80mg eow regimen vs a standard intensification regimen. Conclusions ADA intensification to 80mg eow was safe, effective and did not increase drug costs vs standard intensification to 40mg ew in our experience. •What is already known? Inadequate or loss of response to adalimumab in patients with inflammatory bowel disease can be managed by intensification of treatment to 40 mg every week. •What is new here? Treatment intensification to an alternative regimen of adalimumab 80 mg every other week was safe and effective in a real-world setting with high rates of clinical and biologic remission and no serious infections, hospitalisations or deaths. •How can this study help patient care? These results provide confidence that this alternative intensification regimen is safe and effective for patients with IBD experiencing inadequate or loss of response to adalimumab.

A 65 years old woman presented to the dental practice complaining of hypersensitivity and loss of tooth structure and wishing to improve the esthetics of the anterior region. During clinical examination, wear facets were observed in anterior and posterior regions. Digital Smile Design analysis was carried out in order to predict and plan the final smile design. After removing the previous fillings and with the help of a diagnostic wax up, a clear silicone splint was prepared and filled with Ceram X duo (Dentsply DeTrey, Konstanz, Germany) microhibrid composite which was used to increase the vertical dimension of the patient. The palatal surface of anterior teeth and occlusal surfaces of posterior teeth were restored with composite. Finally, the buccal surfaces of 1.3 to 2.5 were prepared for feldsphatic coreless veneers (Noritake, Japan) and were cemented with light-curing cement calibra and the XP Bond (Dentsply DeTrey, Konstanz, Germany) adhesive. The abutments 1.5 and 1.6 were prepared for the fitting of the partial fixed denture from 1.4 to 1.6. Conclusions After the treatment, the dental hypersensibility subside, so the functional and aesthetic expectations of both, patient and dentist were met.