Potency evaluation of different GNRH analogues on ovulation induction and reproductive performance of doe rabbit.

Gonadotropin-releasing hormone (GnRH) -supplemented extenders have emerged as a welfare-orientated method to induce ovulation in the artificial insemination (AI) of rabbits. The main factor that limits the bioavailability of GnRH analogue on intravaginal administration is the proteolytic activity of enzymes present in rabbit seminal plasma. The use of GnRH analogues with higher biological potency would allow us to decrease their concentration in the seminal dose without compromising effectiveness. The current study was designed to assess the efficacy of various GnRH analogues concerning their ability to induce ovulation in rabbit AI. The base solution used for experimental extenders contained an aminopeptidase inhibitor. Four experimental groups were used, females from the Control group were induced to ovulate with an intramuscular administration of 1 µg of buserelin, while in the other three groups females received an intravaginal administration of 3.5 µg of buserelin (BUS), deslorelin (DES) or fertirelin (FER) within the seminal dose. Results showed that the ovulation frequency was similar in all groups studied. A concentration of 3.5 µg of the different GnRH analogues tested in this study showed similar potency in inducing ovulation in non-lactating females, yielding comparable results in terms of pregnancy rate at birth and prolificacy.

Coastal warming under climate change: Global, faster and heterogeneous.

The assessment of expected changes in coastal sea surface temperature (SST) on a global scale is becoming increasingly important due to the growing pressure on coastal ecosystems caused by climate change. To achieve this objective, 17 Global Climate Models from CMIP6 were used, with data from historical and hist-1950 experiments spanning 1982-2050. This analysis highlights significant warming of coastal areas worldwide, with higher and more variable rates of warming than observed in previous decades. All basins are projected to experience an increase in coastal SST near 1 °C by mid-century, with some regions exhibiting nearshore SST anomalies exceeding 2 °C for the period 2031-2050 relative to 1995-2014. Regarding the Eastern Upwelling Boundary Systems, only the Canary upwelling system and the southern part of the Humboldt upwelling system manage to show lower-than-average SST warming rates, maintaining, to a certain extent, their ability to buffer global warming.

Oocyte quality and in vivo embryo survival after ovarian stimulation in nulliparous and multiparous rabbit does.

Superovulation treatments aim to stimulate multifollicular recruitment, maximizing the number of oocytes or transferable embryos produced. Factors associated with the superovulation protocol, female characteristics and many other factors are determinants in the number and quality of oocytes obtained. An accurate way to assess oocyte quality more precise than morphological appearance is genetic expression. The present study aims to compare the response of nulliparous and multiparous females to superovulatory stimulation, studying its effect on the expression of some genes associated with the activation, growth, development and oocyte-embryo transition of oocytes, as well as its impact on in vivo embryonic development and viability rate at birth. In a first experiment, the effect of stimulation treatment on the ovulation response and the expression of the MSY2, MATER, ITPR1, ITPR2, ITPR3, eIF4E, PAR1, PAPOL-A, PAPOL-G, ZAR1 and YY1 genes in nulliparous and multiparous females were determined. In a second experiment, the implantation and viability at birth of embryos from superovulated nulliparous and multiparous females were analysed. The ovulation rate was significantly higher in the superovulation groups than in the control groups. The ovulation rate was significantly increased in nulliparous females compared with multiparous does. From the eleven genes analysed, only the expression of MATER, PAPOL-A, PAPOL-G and ZAR-1 genes was shown to be different among experimental groups. Finally, in terms of implantation rate and viability at birth, the nulliparous control group showed better results than the rest of the groups. Both hyperstimulation treatment and reproductive female's history seem to alter the transcriptome of important genes related to oocyte maturation and competence acquisition, affecting in vivo embryo viability.

Effects of residential greenness on attention in a longitudinal study at 8 and 11-13 years.

In an urbanizing world, with 55% of the population living in cities, it is essential to design friendly and healthy ones. An emerging body of evidence has associated greenspace exposure with improved cognitive development, including attentional function; however, the longitudinal studies looking at the association with attentional function are still scarce. Therefore, the objective of this study was to analyze the association of the exposure to greenspace and attention in school children. This study was based on 751 participants at 8 years and 598 at 11-13 years of two sub-cohorts of the INMA cohort study in Gipuzkoa and Asturias, Spain. Greenspace exposure at home was characterized using four indicators: (i) average of Normalized Difference Vegetation Index (NDVI) and (ii) Vegetation Continuous Field (VCF) in buffers of 100 m, 300 m, and 500 m around the residential address, (ii) availability of a green space within 300 m from the residential address, and (iv) residential distance to green spaces. Participants' attention was characterized twice at ages of 8 and 11 years, using the computerized Attentional Network Test (ANT). General linear models were used for the cross-sectional analyses and linear mixed effects model for the longitudinal analyses. Our cross-sectional analyses showed a statistical significant protective association between average NDVI at 300 m and inattentiveness (-7.20, CI 95%: 13.74; -0.67). In our longitudinal analyses, although we generally observed beneficial associations between greenspace exposure and attention, none attained statistical significance. No statistically significant indirect effect were seen for NO2. Our findings add to the emerging body of evidence on the role of green spaces in neurodevelopment, which can provide the evidence base for implementing intervention aimed at promoting neurodevelopment in urban children.

PI3K inhibition by BKM120 results in anti-proliferative effects on corticotroph tumor cells.

PURPOSE: Cushing's disease is associated with significant morbidity; thus, additional tumor-directed drugs with the potential to exert antineoplastic effects on corticotroph adenoma cells are desired. The phosphoinositide-3-kinase (PI3K)/protein kinase B (AKT) pathway, which plays regulatory role in cell survival and proliferation, is activated in pituitary adenomas. The present study evaluated the effects of BKM120 (Buparlisib), an oral PI3K inhibitor, on cell viability, apoptosis, cell cycle phase distribution, and ACTH production in mouse corticotroph tumor cells. METHODS: AtT-20/D16v-F2 mouse pituitary corticotroph tumor cells were treated with increasing concentrations of BKM120 or vehicle. Cell viability was measured using an MTS-based assay. Apoptosis was evaluated by Annexin V staining. Cell cycle analysis was performed by propidium iodide DNA staining and flow cytometry. Gene expression of cell cycle regulators (Cdkn1b, Ccnd1, Ccne1, Cdk2, Cdk4, Myc, and Rb1) was assessed by qPCR. Protein expression of p27, total and phosphorylated Akt was assessed by Western blot. ACTH levels were measured in the culture supernatants by chemiluminescent immunometric assay. RESULTS: Treatment with BKM120 decreased AtT-20/D16v-F2 cell viability, induced a G0/G1 cell cycle arrest, reduced the phosphorylation of Akt at Serine 473, and increased p27 expression. Furthermore, BKM120 treatment diminished ACTH levels in the cell culture supernatants. CONCLUSION: In vitro inhibition of PI3K/AKT pathway by BKM120 resulted in anti-proliferative effects on corticotroph tumor cells, decreasing cell viability and ACTH production. These encouraging findings shape the path for further experiments with the inhibition of PI3K/AKT pathway in Cushing's disease.

Real-world use of mycophenolate mofetil in inflammatory bowel disease: Results from the ENEIDA registry.

BACKGROUND: Studies to evaluate the use of mycophenolate mofetil (MMF) in inflammatory bowel disease (IBD) are limited after the appearance of biological treatments. AIMS: Our primary objective was to evaluate the effectiveness and safety of MMF in IBD. METHODS: IBD patients who had received MMF were retrieved from the ENEIDA registry. Clinical activity as per the Harvey-Bradshaw Index (HBI), partial Mayo score (pMS), physician global assessment (PGA) and C-reactive protein (CRP) were reviewed at baseline, at 3 and 6 months, and at final follow-up. Adverse events and causes of treatment discontinuation were documented. RESULTS: A total of 83 patients were included (66 Crohn's disease, 17 ulcerative colitis), 90% of whom had previously received other immunosuppressants. In 61% of patients systemic steroids were used at initiation of MMF, and in 27.3% biological agents were co-administered with MMF. Overall clinical effectiveness was observed in 64.7% of the population. At the end of treatment, 45.6% and 19.1% of subjects showed remission and clinical response, respectively. MMF treatment was maintained for a median of 28.9 months (IQR: 20.4-37.5). CONCLUSION: Our study suggests, in the largest cohort to date, that MMF may be an effective alternative to thiopurines and methotrexate in IBD.

Vitamin D3 levels in women and factors contributing to explain metabolic variations.

The elucidated metabolism of vitamin D3 in humans has been the support to explain the high involvement of this liposoluble vitamin in physiological functions. Clinical studies have associated levels of vitamin D3 metabolites with several disorders. Despite this knowledge, there is a controversy regarding the estimation of deficiency and the physiological and supraphysiological levels of vitamin D3 metabolites. The association between serum concentrations of vitamin D3 metabolites and several potentially influential factors (namely, age and anthropometric, seasonal, spatial and metabolic factors) is analyzed in this study. For this purpose, 558 women were recruited and interviewed in several Spanish provinces before blood sampling. Serum vitamin D3 and its metabolites were determined using an SPE-LC-MS/MS platform. The concentration range for vitamin D3 was 1.7-21.1 nmol/L and was influenced by body mass index (BMI), waist-to-hip ratio (WHR) and seasonal period. 25-hydroxyvitamin D3 levels were within 4.8-147.2 nmol/L and were related to WHR, season, latitude and calcium intake. The range of 24,25-dihydroxyvitamin D3, 0.3-15.0 nmol/L, was associated to BMI, WHR, season, latitude and calcium intake. Finally, energy intake influenced the vitamin D 25-hydroxylase through the 25-hydroxyvitamin D3/vitamin D3 ratio, which regulates the synthesis of the circulating form. According to these results, it is worth emphasizing the relevance of all these factors to explain the variability in serum levels of vitamin D3 and its metabolites. All these factors should be considered in future studies assessing the alteration of vitamin D3 metabolism.

Bacteria and virulence factors in periapical lesions associated with teeth following primary and secondary root canal treatment.

AIM: This cross-sectional study aimed to investigate the microbial profile and to quantify the levels of endotoxins (LPS) and lipoteichoic acid (LTA) present in periapical lesions associated with root filled teeth and those that had received root canal retreatment. It also aimed to investigate the association between microorganisms and their virulence factors with clinical and radiographic features. METHODOLOGY: Patients with periapical lesions in teeth with post-treatment endodontic disease following primary root canal treatment (n = 19) and unsuccessful root canal retreatment (n = 13) were treatment planned for endodontic microsurgery, where the periapical lesions were collected. Clinical and radiographic data were also collected. For microbiological analysis, nested polymerase chain reaction was used to detect 17 bacterial species. Levels of LPS and LTA were determined using limulus amebocyte lysate and enzyme-linked immunosorbent assays, respectively. The Student t-test or Wilcoxon-Mann-Whitney tests were applied to compare the data on LPS and LTA with clinical and radiographic features. The associations between the clinical and radiographic features and the bacterial species were analysed using the Fisher's exact test. A significance level of 5% was adopted. RESULTS: Bacterial DNA, LPS and LTA were detected in all samples. Parvimonas micra was the most commonly detected species in all groups, followed by Enterococcus faecalis, Fusobacterium nucleatum and Porphyromonas endodontalis. The type of endodontic treatment, whether a primary root canal treatment or retreatment, was not associated with the presence of any bacterial species in periapical lesions. The levels of LPS and LTA in periapical lesions of root filled teeth were not significantly different from those that had been retreated. Associations between the levels of LPS and LTA with clinical signs and symptoms were found. No association was found between specific bacteria and clinical features. CONCLUSION: Periapical lesions associated with teeth after primary root canal treatment and retreatment had similar polymicrobial composition. The levels of LPS and LTA in periapical lesions associated with teeth after primary root canal treatment and retreatment were similar, and both were associated with the same symptomatology.

Lipidomics: An omics discipline with a key role in nutrition.

The importance of lipidomics to unveil crucial aspects in the nutrition field is afforded in this article. With this aim, historical facts such as demonization of fats, enthronization of carbohydrates, and subsequent changes in the food pyramid are first discussed. After considering basic and analytical aspects of lipidomics and the upstream information this omics provides, its key role in personalized nutrition (PN), and the importance of lipids as nutrition biomarkers are critically discussed by appropriate examples. Pendent challenges to clarify the role of lipidomics in nutrition are overcome limiting factors, design of new lipidomics-based biomarkers, unveil mechanisms involved in lipidomics processes, and integrate lipidomics with other omics for a more complete and validated information useful in PN. The conclusions of this study also include the scant role of analytical chemists in the lipidomics-nutrition binomial, basically supported on analytical data.

[Masks as personal protective equipment in the COVID-19 pandemic: How, when and which should be used]. / Mascarillas como equipo de protección individual durante la pandemia de COVID-19: cómo, cuándo y cuáles deben utilizarse.

BACKGROUND AND OBJECTIVE: In the COVID-19 pandemic, the demand of masks has been increased by health professionals and the general population. In this context, it is necessary to summarize the features and indications of the different types of masks. MATERIAL AND METHODS: To consult and to compile the different recommendations disseminated by prestigious institutions such as the World Health Organization, the European Center for Disease Prevention, the Center for Evidence-Based Medicine, or the Ministry of Health of the Government of Spain has been reviewed. RESULTS: The institutions consulted recommend reserving FFP respirators for healthcare workers, especially when carrying out aerosol-generating procedures (AGPs) (minimum FFP2 protection) and consider some reutilization systems during times of scarcity. The use of surgical masks is recommended to professionals who do not perform AGPs and to the symptomatic population but exist variations in its indications intended for the general healthy population. CONCLUSION: In the context of shortage of personal protective equipment due to the COVID-19 pandemic, a prioritization and rationalization of the use of each type of mask should be established according to the user and the activity performed.

Dry sweat as sample for metabolomics analysis.

Sweat is gaining popularity in clinical metabolomics as this biofluid is non-invasively sampled and its composition is modified by several pathologies. There is a lack of standardized strategies for collection of human sweat. Most studies have been carried out with fresh sweat collected after stimulation. A promising and simple alternative is sampling dry sweat by a solid support impregnated with a suited solvent. This research was aimed at comparing the metabolomics coverage provided by dry sweat collected by two solid supports (gauzes and filter papers) impregnated with different solvents. The dissolved dry sweat was analyzed by a dual approach: gas chromatography-mass spectrometry (GC-MS) and liquid chromatography-tandem mass spectrometry (LC-MS/MS). Among the tested sampling strategies, filter paper impregnated with 1:1 (v/v) ethanol‒phosphate buffer resulted the combination providing the highest metabolomics coverage (tentative identification of one hundred seventy-five compounds). Dry and fresh sweat were compared by using pools from the same individuals to evaluate compositional differences. Families of metabolites such as carnitines, sphingolipids and N-acyl-amino acids, among others, were exclusively identified in dry sweat. Comparison of both samples allowed concluding that dry sweat is better for analysis of low polar metabolites and fresh sweat is more suited for polar compounds. As most of the identified metabolites are involved in key biochemical pathways, this study opens interesting possibilities to the use of dry sweat as a source of metabolite markers for specific disorders. Sampling of dry sweat could provide a standardized approach for collection of this biofluid, thus overcoming the variability limitations of fresh sweat.

The role of analytical chemists in the research on the cultural heritage.

Professionals belonging to very different areas of expertise are usually involved in research on the cultural heritage. Among the names given to the person in charge of analyses are conservator or material scientist, as the most usual, but never "analytical chemist", despite analytical equipment, obtainment of analytical data and application of chemometrics approaches to obtain analytical results are always involved in their tasks. This article tries to be a call of attention to analytical chemists by showing the different areas within the research on cultural heritage in which they should be involved to provide the necessary analytical information. Examples of the analytical equipment involved in these studies, the research on pigments, dyes, binders and coatings, dating and cleaning of artworks are given, thus showing that analytical information on chemical aspects related to research on the cultural heritage should be, evidently, conducted in cooperation with analytical chemists.

Linear and volumetric gain after vertical bone augmentation in the posterior mandible using an autologous cortical tenting method.

This study was performed to evaluate the linear and volumetric effects of a technique for reconstruction of the posterior atrophic mandible, including the final bone gain of the graft, by three-dimensional assessment. Thirteen individuals were recruited into the study and submitted to a total of 15 mandibular autogenous bone block surgeries. Cone beam computed tomography images were obtained at three different times. Bone graft length and thickness, and the volume, height, and width of the graft were measured. Data were compared statistically among the time points using the Friedman test, and cluster analysis was performed to identify the association between the study variables and the resorption rate (α = 0.05). Linear analysis of the width and height of the recipient area at the different time points revealed a statistically significant difference. The final average increase in height was 1.6 mm; all subjects showed an average volume gain of 3.412mm3, and 77% of the subjects showed an average graft resorption of 0.688mm3 construction of three-dimensional vertical defects of the posterior mandible resulted in good healing with minimal complications and minimal bone graft resorption, favouring vertical bone gain.

Effectiveness and Safety of the Switch from Remicade® to CT-P13 in Patients with Inflammatory Bowel Disease.

BACKGROUND AND AIMS: To evaluate the clinical outcomes in patients with IBD after switching from Remicade® to CT-P13 in comparison with patients who maintain Remicade®. METHODS: Patients under Remicade® who were in clinical remission with standard dosage at study entry were included. The 'switch cohort' [SC] comprised patients who made the switch from Remicade® to CT-P13, and the 'non-switch' cohort [NC] patients remained under Remicade®. RESULTS: A total of 476 patients were included: 199 [42%] in the SC and 277 [58%] in the NC. The median follow-up was 18 months in the SC and 23 months in the NC [p < 0.01]. Twenty-four out of 277 patients relapsed in the NC; the incidence of relapse was 5% per patient-year. The cumulative incidence of relapse was 2% at 6 months and 10% at 24 months in this group. Thirty-eight out of 199 patients relapsed in the SC; the incidence rate of relapse was 14% per patient-year. The cumulative incidence of relapse was 5% at 6 months and 28% at 24 months. In the multivariate analysis, the switch to CT-P13 was associated with a higher risk of relapse (HR = 3.5, 95% confidence interval [CI] = 2-6). Thirteen percent of patients had adverse events in the NC, compared with 6% in the SC [p < 0.05]. CONCLUSIONS: Switching from Remicade® to CT-P13 might be associated with a higher risk of clinical relapse, although this fact was not supported in our study by an increase in objective markers of inflammation. The nocebo effect might have influenced this result. Switching from Remicade® to CT-P13 was safe.

Evaluation of short-term storage prior to analysis of vitamin D3 and metabolites in human serum by liquid chromatography coupled to tandem mass spectrometry.

Vitamin D has been widely determined in clinical trials to elucidate its biochemical involvement in a great number of pathologies. The analysis of vitamin D and its hydroxymetabolites in biofluids such as serum or plasma is a challenging task due to limitations associated to the low concentrations of some metabolites (typically, dihydroxymetabolites), methodological interferences, and the low stability of the compounds. Among these limitations, efforts have been targeted at optimizing instrumental improvements to develop more sensitive and selective methods, while the stability of vitamin D and metabolites has not been exhaustively evaluated. In this research, several aspects regarding the short-term storage conditions of human serum have been studied to evaluate their influence on the determination of vitamin D3 and metabolites. An experimental plan has been applied to assess the influence of two relevant parameters: the storage temperature for a period of two months and the number of freeze-thaw cycles. The storage temperature affected in a different manner to vitamin D3 and its metabolites, being vitamin D3 and 1,25-dihydroxyvitamin D3 the two analytes more affected by this parameter. Concerning the freeze-thaw cycles, this variable must be limited to two cycles owing to its significant influence on the variability for quantitation of dihydroxymetabolites in human serum. Finally, lyophilization was also tested to check if serum concentrations of vitamin D3 and its metabolites were affected by this preprocessing step. The results revealed that only vitamin D3 experienced a decrease in serum concentration after two months, which does not constitute a real problem as vitamin D3 is not currently a crucial parameter to be determined in clinical trials due to its scant biological activity.

Outcomes of laparoscopic management of multicompartmental pelvic organ prolapse.

BACKGROUND: Pelvic organ prolapse (POP) is an increasing medical problem with complex diagnostics and controversial surgical management. It causes a series of dysfunctions in the gynecological, urinary, and anorectal organs. Numerous procedures have been proposed to treat these conditions, but in recent years, ventral mesh rectocolposacropexy (VMRCS) has emerged as the procedure of choice for the surgical treatment of POP, especially by a laparoscopic approach. This surgical technique limits the risk of autonomic nerve damage, and the colpopexy allows the correction of concomitant prolapse of the middle compartment. However, symptoms derived from anterior compartment prolapse remain a major morbidity and sometimes require an additional procedure. The aim of this study is to evaluate the results of laparoscopic prosthetic rectocolposacropexy (LRCS) and colposacropexy (LCS) procedures performed to manage combined multicompartmental POP. METHODS: Between November 2008 and December 2017, 38 patients with symptomatic POP underwent rectocolposacropexy (RCS) or colposacropexy (CS) by a laparoscopic approach. Demographics, mortality, morbidity, hospital stay, and functional outcomes were retrospectively analyzed. RESULTS: The median operating time was 200 min (IQR 160-220). Additional simultaneous surgery for POP was performed in nine cases: five suburethral slings and four hysterectomies were performed. No mortality was recorded. The conversion rate was 7.89%. There were two intraoperative complications (5.26%): one enterotomy and one urinary bladder tear. Late complications occurred in 5.26% of cases. After a mean follow-up of 20 months, constipation was completely resolved or improved in 83.33% of patients, urinary stress incontinence was resolved or improved in 52.94%, and gynecological symptomatology was resolved or improved in 93.75%. The recurrence rate was 5.26%. CONCLUSIONS: Laparoscopic mesh rectocolposacropexy and colposacropexy are safe and effective techniques associated with very low morbidity. In the medium term, they provide good results for POP and associated symptoms, but urinary symptomology has a worse outcome.

Determination of primary fatty acid amides in different biological fluids by LC-MS/MS in MRM mode with synthetic deuterated standards: Influence of biofluid matrix on sample preparation.

The recent growing interest in primary fatty acid amides (PFAMs) is due to the broad range of physiological effects they exhibit as bioindicator of pathological states. These bioactive lipids are usually in biological samples at the nanomolar level, making their detection and identification a challenging task. A method for quantitative analysis of seven main PFAMs (lauramide, myristamide, linoleamide, palmitamide, oleamide, stearamide and behenamide) in four human biofluids -namely, urine, plasma, saliva and sweat- is here reported. Two sample preparation procedures were compared to test their efficiency in each biofluid: solid-phase extraction (SPE) and protein precipitation. The latter was the best for plasma and urine, while the analysis of saliva and sweat required an SPE step for subsequent suited determination of PFAMs. Detection of the seven metabolites was performed by liquid chromatography coupled to tandem mass spectrometry (LC-MS/MS) in multiple reaction monitoring (MRM) mode. Quantitative analysis was supported on the use of stable isotopically labeled internal standards (SIL-ISs) in the calibration method, which required the synthesis of each IS from the precursor deuterated fatty acids. Detection limits for the target analytes were within 0.3-3 ng mL-1. The method was applied to a small cohort of male and female volunteers (n = 6) to estimate the relative concentration profiles in the different biofluids. The analytical features of the method supported its applicability in clinical studies aimed at elucidating the role of PFAMs metabolism.

[Critically ill patient isolation: risk or protection?] / Aislamiento del paciente crítico: ¿riesgo o protección?

INTRODUCTION: Isolation precautions are an effective measure to prevent the spread of multi-resistant microorganisms (MMR). However, its implementation is complex and can increase some risks to the patient. The aim of this study is to determine whether the implementation of isolation precautions increase the risk of patient safety incidents (PSI) in critically ill patients. MATERIAL AND METHODS: A retrospective observational study was conducted involving patients admitted to the ICU of a University Hospital, and that required isolation for more than 48h. Period of study: two years (from 2013/03/01 to 2015/03/31). Data source was the electronic medical record. The tools for evaluation were the Modular Review Form questionnaires (MRF1 and MRF2). An analysis was made of PSI and adverse events (AEs) during periods with and without isolation precautions, including the PSI type, severity, and preventability. RESULTS: The study included a total of 76 patients, 74 of whom had at least one PSI. A total of 798 PSI were detected (511 during isolation period), 599 were a No harm incident (NHI) and 199 were adverse AEs. The most frequent PSIs were associated with medication (316) and patient health care (279). Most of them were moderately or highly preventable. The incidence of PSI during periods with and without isolation was 27.3 (SD 33.8) and 29 (39.6) per 100 patient-days, respectively. CONCLUSIONS: PSIs in ICU are frequent, and the most of them are preventable. The adoption of isolation precautions does not constitute a risk factor for PSI. Improving patient safety culture is essential for an adequate prevention strategy.

Short and long-term effectiveness and safety of vedolizumab in inflammatory bowel disease: results from the ENEIDA registry.

BACKGROUND: Effectiveness of vedolizumab in real world clinical practice is unknown. AIM: To evaluate the short and long-term effectiveness of vedolizumab in patients with inflammatory bowel disease (IBD). METHODS: Patients who received at least 1 induction dose of vedolizumab were included. Effectiveness was defined based on Harvey-Bradshaw index (HBI) in Crohn's disease (CD) and Partial Mayo Score (PMS) in ulcerative colitis (UC). Short-term response was assessed at week 14. Variables associated with short-term remission were identified by logistic regression analysis. The Kaplan-Meier method was used to evaluate the long-term durability of vedolizumab treatment. Cox model was used to identify factors associated with discontinuation of treatment and loss of response. RESULTS: 521 patients were included (median follow-up 10 months [interquartile range 5-18 months]). At week 14, 46.8% had remission and 15.7% clinical response. CD (vs UC), previous surgery, higher CRP concentration and disease severity at baseline were significantly associated with impaired response. The rate of vedolizumab discontinuation was 37% per patient-year of follow-up (27.6% in UC and 45.3% in CD, P < 0.01). CD (vs UC), anaemia at baseline, steroids during induction and CRP concentration were associated with lower durability of treatment. Seven per cent of patients developed adverse events, infections being the most frequent. CONCLUSIONS: Over 60% of IBD patients respond to vedolizumab. Many patients discontinue treatment over time. CD and disease burden impair both short- and long-term response. Vedolizumab seems to be safe in clinical practice.

Collagen V oral administration decreases inflammation and remodeling of synovial membrane in experimental arthritis.

Because collagen type V (Col V) can be exposed in tissue injury, we hypothesized that oral administration of this collagen species modulates the inflammation and remodeling of experimental synovitis, avoiding joint destruction, and that the modulation may differ according to the temporal administration. Arthritis (IA, n = 20) was induced in Lewis rats by intraarticular (ia) injection of 500 µg of methylated bovine serum albumin (mBSA) emulsified in complete Freund's adjuvant (CFA) (10 µl) followed by an intraarticular booster of mBSA (50 µg) in saline (50 µl) administered at 7 and 14 days. The control group received saline (50 µl, ia). After the first intraarticular injection, ten IA animals were supplemented via gavage with Col V (500 µg/300 µl) daily for 30 days (IA/Suppl). The control group received saline (50 µL) and Col V supplement in the same way (Suppl). Col V oral administration in IA/Suppl led to 1) inhibited edema and severe inflammatory cell infiltration, 2) decreased collagen fiber content, 3) decreased collagen type I, 4) inhibited lymphocyte subpopulations and macrophages, 5) inhibited IL-1ß, IL-10, IL-17 and TNF-α production and 6) increased expression of caspase-9 in the synovial tissue. In conclusion, Col V supplementation decreased synovial inflammation and the fibrotic response, possibly by increased the apoptosis of inflammatory cells.