Identification of circulating autoantibodies to non-modified proteins associated with ACPA status in early rheumatoid arthritis.

OBJECTIVES: To discover autoantibodies to non-modified proteins associated with the presence/absence of anticitrullinated protein antibodies (ACPA) in rheumatoid arthritis (RA). METHODS: The autoantibody repertoire of 80 ACPA negative and 80 ACPA positive RA subjects from the Swedish population-based Epidemiological Investigation of RA (EIRA) cohort was screened using a suspension bead array built on protein fragments earlier described as autoimmunity targets. Four autoantibodies positive in the initial screening were validated in another set of EIRA samples containing 317 ACPA-positive, 302 ACPA-negative and 372 age- and sex-matched controls. The relationship between the four autoantibodies and lung abnormalities on high-resolution computed tomography (HRTC) was examined in 93 early RA patients from LURA cohort. Association between the autoantibodies, smoking and MHC class II alleles was assessed by logistic regression analysis. RESULTS: : Anti-ANOS1 and anti-MURC IgG levels were associated with ACPA-positive status (OR = 3.02; 95% CI 1.87-4.89; and OR = 1.86; 95% CI 1.16-2.97, respectively) and increased in ACPA-positive patients compared with controls. Anti-ANOS1 IgG was associated with smoking habit (OR = 2.11; 95% CI 1.22-3.69) and anti-MURC IgG with the presence of the MHC class II "shared-epitope" genes (OR = 1.95; 95% CI 1.11-3.46). Anti-TSPYL4 IgG was associated with ACPA-negative (OR = 0.41; 95% CI 0.19-0.89). Anti-TSPYL4 IgG and anti-MAP2K6 IgG levels were increased in the ACPA-negative patients compared with controls. Presence of anti-MAP2K6 IgG and anti-TSPYL4 IgG correlated negatively with HRCT-defined lung abnormalities. CONCLUSIONS: These four autoantibodies may be useful in diagnostics and in predicting clinical phenotypes of RA.

Bioinspired Synthesis of Magnetic Nanoparticles Based on Iron Oxides Using Orange Waste and Their Application as Photo-Activated Antibacterial Agents.

Magnetic nanoparticles based on iron oxides (MNPs-Fe) have been proposed as photothermal agents (PTAs) within antibacterial photothermal therapy (PTT), aiming to counteract the vast health problem of multidrug-resistant bacterial infections. We present a quick and easy green synthesis (GS) to prepare MNPs-Fe harnessing waste. Orange peel extract (organic compounds) was used as a reducing, capping, and stabilizing agent in the GS, which employed microwave (MW) irradiation to reduce the synthesis time. The produced weight, physical-chemical features and magnetic features of the MNPs-Fe were studied. Moreover, their cytotoxicity was assessed in animal cell line ATCC RAW 264.7, as well as their antibacterial activity against Staphylococcus aureus and Escherichia coli. We found that the 50GS-MNPs-Fe sample (prepared by GS, with 50% v/v of NH4OH and 50% v/v of orange peel extract) had an excellent mass yield. Its particle size was ~50 nm with the presence of an organic coating (terpenes or aldehydes). We believe that this coating improved the cell viability in extended periods (8 days) of cell culture with concentrations lower than 250 µg·mL-1, with respect to the MNPs-Fe obtained by CO and single MW, but it did not influence the antibacterial effect. The bacteria inhibition was attributed to the plasmonic of 50GS-MNPs-Fe (photothermal effect) by irradiation with red light (630 nm, 65.5 mW·cm-2, 30 min). We highlight the superparamagnetism of the 50GS-MNPs-Fe over 60 K in a broader temperature range than the MNPs-Fe obtained by CO (160.09 K) and MW (211.1 K). Therefore, 50GS-MNPs-Fe could be excellent candidates as broad-spectrum PTAs in antibacterial PTT. Furthermore, they might be employed in magnetic hyperthermia, magnetic resonance imaging, oncological treatments, and so on.

Exploring High-Throughput Immunoassays for Biomarker Validation in Rheumatic Diseases in the Context of the Human Proteome Project.

Rheumatic diseases are high prevalence pathologies with different etiology and evolution and low sensitivity in clinical diagnosis. Therefore, it is necessary to develop an early diagnosis method which allows personalized treatment, depending on the specific pathology. The biology/disease initiative, at Human Proteome Project, is an integrative approach to identify relevant proteins in the human proteome associated with pathologies. A previously reported literature data mining analysis, which identified proteins related to osteoarthritis (OA), rheumatoid arthritis (RA), and psoriatic arthritis (PSA) was used to establish a systematic prioritization of potential biomarkers candidates for further evaluation by functional proteomics studies. The aim was to study the protein profile of serum samples from patients with rheumatic diseases such as OA, RA, and PSA. To achieve this goal, customized antibody microarrays (containing 151 antibodies targeting 121 specific proteins) were used to identify biomarkers related to early and specific diagnosis in a screening of 960 serum samples (nondepleted) (OA, n = 480; RA, n = 192; PSA, n = 288). This functional proteomics screening has allowed the determination of a panel (30 serum proteins) as potential biomarkers for these rheumatic diseases, displaying receiver operating characteristics curves with area under the curve values of 80-90%.

Effectiveness of Therapeutic Exercise and Patient Education on Cancer-Related Fatigue in Breast Cancer Survivors: A Randomised, Single-Blind, Controlled Trial with a 6-Month Follow-Up.

This study aimed to determine the effectiveness of therapeutic exercise plus patient therapeutic education on perceived fatigue, functional capacity and pain in breast cancer survivors with cancer-related fatigue. A randomised, single-blind, clinical trial was conducted with a total of 80 breast cancer survivors who presented cancer-related fatigue. Women were randomised into a supervised therapeutic exercise group (STE-G) (n = 40) or an unsupervised exercise group (UE-G) (n = 40). Both interventions included patient therapeutic education and were delivered in three sessions per week over eight weeks. The main outcome was perceived fatigue as assessed by the Spanish version of the Functional Assessment of Chronic Illness Therapy-Fatigue subscale (FACIT-F). Other evaluated outcomes were pain measured on a visual analogue scale, and distance measured using the 6-Minute Walk Test. Data were collected at baseline, immediately post-intervention, and at three and six months after baseline. Significantly greater improvements across all variables were observed in the STE-G throughout the entire follow-up period with the exception of pain. Conclusions: A supervised therapeutic exercise program plus patient therapeutic education significantly reduce perceived fatigue and increase functional capacity in breast cancer survivors suffering from cancer-related fatigue compared to an unsupervised physical exercise program based on individual preferences with patient therapeutic education.

Low-grade triple-negative breast carcinomas. A report of 2 cases and an update of current concepts.

Triple negative breast cancer is defined by the lack of expression of estrogen, progesterone and HER2 receptors. Significant molecular, morphological and clinical heterogeneity is present in this group of neoplasms. Although the majority are high-grade tumors, low-grade triple negative breast cancers can occur and their evolution, molecular characteristics and therapeutic management vary from the former. In the current review, we focus on the histological and immunohistochemical phenotypes of two new low-grade cases: an acinic cell carcinoma and an adenoid cystic carcinoma. Data originated from the pathology department of a third-level hospital over an 18-month period, within a breast cancer screening program. Low-grade triple negative cancers should be suspected in triple negative breast cancers with low proliferative rates as, unlike high-grade tumors, they require a multidisciplinary approach. They can be diagnosed at an early stage by immunohistochemistry using core needle biopsy.

Quality of Colonoscopy Is Associated With Adenoma Detection and Postcolonoscopy Colorectal Cancer Prevention in Lynch Syndrome.

BACKGROUND & AIMS: Colonoscopy reduces colorectal cancer (CRC) incidence and mortality in Lynch syndrome (LS) carriers. However, a high incidence of postcolonoscopy CRC (PCCRC) has been reported. Colonoscopy is highly dependent on endoscopist skill and is subject to quality variability. We aimed to evaluate the impact of key colonoscopy quality indicators on adenoma detection and prevention of PCCRC in LS. METHODS: We conducted a multicenter study focused on LS carriers without previous CRC undergoing colonoscopy surveillance (n = 893). Incident colorectal neoplasia during surveillance and quality indicators of all colonoscopies were analyzed. We performed an emulated target trial comparing the results from the first and second surveillance colonoscopies to assess the effect of colonoscopy quality indicators on adenoma detection and PCCRC incidence. Risk analyses were conducted using a multivariable logistic regression model. RESULTS: The 10-year cumulative incidence of adenoma and PCCRC was 60.6% (95% CI, 55.5%-65.2%) and 7.9% (95% CI, 5.2%-10.6%), respectively. Adequate bowel preparation (odds ratio [OR], 2.07; 95% CI, 1.06-4.3), complete colonoscopies (20% vs 0%; P = .01), and pan-chromoendoscopy use (OR, 2.14; 95% CI, 1.15-3.95) were associated with significant improvement in adenoma detection. PCCRC risk was significantly lower when colonoscopies were performed during a time interval of less than every 3 years (OR, 0.35; 95% CI, 0.14-0.97). We observed a consistent but not significant reduction in PCCRC risk for a previous complete examination (OR, 0.16; 95% CI, 0.03-1.28), adequate bowel preparation (OR, 0.64; 95% CI, 0.17-3.24), or previous use of high-definition colonoscopy (OR, 0.37; 95% CI, 0.02-2.33). CONCLUSIONS: Complete colonoscopies with adequate bowel preparation and chromoendoscopy use are associated with improved adenoma detection, while surveillance intervals of less than 3 years are associated with a reduction of PCCRC incidence. In LS, high-quality colonoscopy surveillance is of utmost importance for CRC prevention.

Intra-individual changes in 3x2 achievement goals, friendship goals, motivational regulations and consequences in physical education / Cambios intraindividuales en las metas de logro 3x2, metas de amistad, regulaciones motivacionales y consecuencias en educación física

Abstract Introduction: This research examines intraindividual changes in 3x2 achievement goals in physical education classes during one semester, as well as the relationship of these changes with those in other motivational and outcome variables. Method: A total of 334 (178 boys and 156 girls) high school students (M = 13.12, SD = 1.05) completed five questionnaires in two different school years. Results: The results of the true intraindividual change model (TIC) provided unequivocal support for the separation of task-based and self-based goals, as well as the structures based on both valences of approach and avoidance. They also showed different intraindividual change patterns in the 3x2 achievement goals, indicating a progression in the stability of the goals depending on their definition. Intraindividual variability in achievement goals is directly related to intraindividual variability in dependent variables, with the task-approach goals TIC being the most adaptive. Conclusions: These goals should be prioritized.

Resumen Introducción: Este artículo examina el cambio intraindividual de las metas de logro 3x2 en las clases de educación física durante un semestre, así como la relación de estos cambios con los producidos en otras variables motivacionales y de resultado. Método: Un total de 334 (178 varones y 156 mujeres) estudiantes de educación secundaria (M = 13.12, DT = 1.05) completaron un cuestionario en dos cursos escolares diferentes. Resultados: Los resultados de la aplicación del modelado del verdadero cambio intraindividual (TIC) proporcionaron un claro apoyo a la separación de las metas basadas en la tarea y en el yo, así como a las estructuras basadas en ambas valencias de aproximación y evitación. También mostraron patrones de cambio intraindividual diferentes en las metas de logro 3x2 que parecen indicar una progresión en la estabilidad de las metas en función de su definición. Se observa que la variabilidad intraindividual en las metas de logro está directamente relacionada con la variabilidad intra individual en otras variables dependientes, siendo el TIC de las metas de aproximación-tarea el más adaptativo. Conclusiones: Se reafirman los beneficios de promover las metas de aproximación-tarea por encima del resto

The Role of Physiotherapy in Pediatric Palliative Care: A Systematic Review.

Pediatric palliative care (PPC) is a set of actions aimed at children who suffer from a severe or life-threatening disease to alleviate the symptoms of the disease and improve the quality of life of both the child and his/her family. One of the tools used to control symptoms is physiotherapy; however, its application in the child population has not been thoroughly studied. The main objective of this study was to gather, analyze, and critically evaluate the available scientific evidence on physiotherapy in children who require palliative care through a systematic review of the studies published in the last 10 years in the following databases: PubMed, Cochrane Library, PEDro, CINAHL, and Scopus. Of a total of 622 studies, the inclusion criteria were only met by seven articles, which were focused on the relationship between physiotherapy and PPC. This study analyzed: (1) the main pathologies treated, with a predominance of cerebral palsy and cancer; (2) the interventions applied, such as respiratory physiotherapy, neurological physiotherapy, therapeutic massage, and virtual reality; (3) the effects achieved in the child and his/her family, highlighting the control of symptoms and the improvement of the quality of life; and (4) the knowledge of the physiotherapists on PPC, observing that most of the professionals had not received training in this scope. The findings of this review indicate a lack of an adequate evidence foundation for physiotherapy in PPC.

Eficacia de la marcha en cinta rodante sobre el desarrollo motor de niños con parálisis cerebral y síndrome de down / Effectiveness of treadmill training on the motor development of children with cerebral palsy and Down syndrome

Resumen La parálisis cerebral y el síndrome de Down son dos afecciones que cursan con déficit del desarrollo motor. Este retraso mejora con el uso de cinta rodante. Se realizó una revisión sistemática en dife rentes bases de datos con el propósito de analizar estudios y s u calidad metodológica en relación a la aplicación del uso exclusivo de cinta rodante y su combinación con otras terapias para fomentar la marcha y equilibrio en niños menores de 12 años con parálisis cerebral y síndrome de Down. Se seleccionaron únicamente ensayos clínicos aleatorizados publicados hasta la fecha en PubMed, PEDro, Cochrane y Science Direct. La calidad me todológica de los estudios identificados se evaluó a través de la escala PEDro. De los 324 artículos inicialmente encontrados, se seleccionaron los 10 que cumplieron con los criterios de inclusión establecidos para su análisis cualitativo. Las variables analizadas fueron la marcha y el equilibrio en ambas poblaciones tras la intervención con cinta rodante, con y sin suspensión del peso corporal. Concluimos que la aplicación de cinta rodante como única herramienta terapéutica resulta una intervención eficaz para favorecer el desarrollo de la marcha y el equilibrio en niños de 0 a12 años con parálisis cerebral y síndrome de Down.

Abstract Cerebral palsy and Down syndrome are two conditions that present with a deficit in motor development. Treadmill interventions were found to improve this delay in development. This work aimed to describe and analyze the methodological quality of studies that applied treadmill interventions alone or combined with other therapies to promote gait and balance in children under 12 years of age with cerebral palsy and Down syndrome. A systematic review was made in different databases: PubMed, PEDro, Cochrane and Science Direct. Only randomized clinical trials published to date were selected. The methodological quality of the identified studies was assessed using the PEDro scale. Of the 324 articles initially found, 10 were selected, which met the established inclusion criteria for qualitative analysis. The variables analyzed were gait and bal ance in both populations after the treadmill intervention, with and without suspension of body weight. The main conclusion was that the application of a treadmill alone is an effective intervention to promote the development of gait and balance in children under 12 years with cerebral palsy and Down syndrome.

Phenolic compounds from virgin olive oil obtained by natural deep eutectic solvent (NADES): effect of the extraction and recovery conditions.

Environmentally friendly natural deep eutectic solvents (NADES) have been shown to efficiently extract a wide range of phenolic compounds from virgin olive oil (VOO). The objective of this work was to optimize the yield of olive oil phenols extracted by NADES based on xylitol/choline choride (Xyl/ChCl). Different extraction and recovery conditions were investigated, including the effect of different extraction operating parameters (temperature, time, VOO:NADES ratio) and subsequent recovery conditions (XAD resin height, wash-water and eluent volume and pH). The highest concentration of phenols (555.36 mg/kg VOO) was obtained from extraction at 40 °C for 1 h, with a 1:1 ratio, using an adsorption resin XAD-16 with bed height of 10 cm, 250 mL acidified wash-water and 300 mL EtOH 100% as eluent. No statistically significant loss of the sum of phenolic compounds was observed when compared with the concentration values obtained by direct analysis in HPLC without the elimination of NADES. Additionally, a sequential desorption with different concentration of ethanol was used to determine the effect of the solvent concentration on polyphenol yield. Polar compounds, such as hydroxytyrosol and tyrosol, were recovered at 81.7% and 83.6%, respectively with 50 and 80% ethanol; however, 100% ethanol was required for the complete elution of oleacein (3,4-DHPEA-EDA) and oleocanthal (p-HPEA-EDA). In this paper we present an effective process for the extraction of polyphenols from VOO by NADES for direct analysis in HPLC and for the recovery and concentration of polyphenols by removing the solvent (NADES) with no losses of yield and solvent recycling.

Noninvasive assessment of liver fibrosis in Crohn's disease patients exposed to methotrexate.

BACKGROUND: Methotrexate is widely used to treat some inflammatory chronic disorders, though it is hampered by the risk of liver fibrosis. Many recommendations have been made to assess methotrexate-related hepatotoxicity, including liver biopsy. However, other noninvasive methods to assess liver fibrosis have been developed and could be implemented for patients treated with methotrexate. AIM: The aim of the study was to compare the prevalence of liver fibrosis by means of noninvasive methods [aspartate transaminase-to-platelet ratio index (APRI) Forns index, and transient elastography] in patients with Crohn's disease exposed or not to methotrexate, and to identify risk factors for liver fibrosis. METHODS: Prospective, cross-sectional study. All patients with Crohn's disease exposed to methotrexate were included and compared to an unselected cohort of outpatients with Crohn's disease never exposed to methotrexate. RESULTS: A total of 84 patients with Crohn's disease, 56 exposed to methotrexate, and 28 controls, were included. Significant liver fibrosis was found in 7% of methotrexate-exposed patients with Crohn's disease and 10% of controls as measured by transient elastography, and in 7% of controls as measured by the Forns index. No cases of liver fibrosis were detected by APRI. Only alcohol consumption, diabetes mellitus, and age were associated with significant liver fibrosis. CONCLUSIONS: Significant liver fibrosis is uncommon among patients with Crohn's disease, even among those exposed to methotrexate. The risk of liver fibrosis in Crohn's disease seems to depend on common risk factors for liver disease.

Colon capsule endoscopy versus CT colonography in FIT-positive colorectal cancer screening subjects: a prospective randomised trial-the VICOCA study.

BACKGROUND: Colon capsule endoscopy (CCE) and CT colonography (CTC) are minimally invasive techniques for colorectal cancer (CRC) screening. Our objective is to compare CCE and CTC for the identification of patients with colorectal neoplasia among participants in a CRC screening programme with positive faecal immunochemical test (FIT). Primary outcome was to compare the performance of CCE and CTC in detecting patients with neoplastic lesions. METHODS: The VICOCA study is a prospective, single-centre, randomised trial conducted from March 2014 to May 2016; 662 individuals were invited and 349 were randomised to CCE or CTC before colonoscopy. Endoscopists were blinded to the results of CCE and CTC. RESULTS: Three hundred forty-nine individuals were included: 173 in the CCE group and 176 in the CTC group. Two hundred ninety individuals agreed to participate: 147 in the CCE group and 143 in the CTC group. In the intention-to-screen analysis, sensitivity, specificity and positive and negative predictive values for the identification of individuals with colorectal neoplasia were 98.1%, 76.6%, 93.7% and 92.0% in the CCE group and 64.9%, 95.7%, 96.8% and 57.7% in the CTC group. In terms of detecting significant neoplastic lesions, the sensitivity of CCE and CTC was 96.1% and 79.3%, respectively. Detection rate for advanced colorectal neoplasm was higher in the CCE group than in the CTC group (100% and 93.1%, respectively; RR = 1.07; p = 0.08). Both CCE and CTC identified all patients with cancer. CCE detected more patients with any lesion than CTC (98.6% and 81.0%, respectively; RR = 1.22; p = 0.002). CONCLUSION: Although both techniques seem to be similar in detecting patients with advanced colorectal neoplasms, CCE is more sensitive for the detection of any neoplastic lesion. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02081742 . Registered: September 16, 2013.

Association of serum anti-centromere protein F antibodies with clinical response to infliximab in patients with rheumatoid arthritis: A prospective study.

BACKGROUND: One-third of rheumatoid arthritis (RA) patients demonstrate no clinical improvement after receiving tumor necrosis factor inhibitors (TNFi). The presence of serum autoantibodies is a hallmark in RA and may provide information on future response to treatment. The aim of this prospective study was to search for novel serum autoantibodies useful to predict clinical response to TNFi. METHODS: The autoantibody repertoire was profiled on RA patients treated with TNFi as a first line of biologic therapy (N = 185), who were recruited in three independent cohorts. The presence and levels of autoantibodies in serum at baseline were analysed in association with the clinical response after 24 weeks follow-up. A multiplex bead array built using antigens selected from an initial untargeted screening was employed to identify the autoantibodies on a discovery cohort (N = 50) and to verify and validate the results on verification (N = 61) and validation (N = 74) cohorts. Non-parametric tests, meta-analysis and Receiver Operating Curves (ROC) were performed in order to assess the clinical relevance of the observed findings. RESULTS: Novel autoantibodies were associated with the clinical response to TNFi, showing different reactivity profiles among the different TNFi. The baseline levels of IgG antibodies against Centromere protein F (CENPF), a protein related to cell proliferation, were significantly (p<0.05) increased in responders (N = 111) to infliximab (IFX) compared to non-responders (N = 44). The addition of anti-CENPF antibodies to demographic and clinical variables (age, sex, DAS28-ESR) resulted in the best model to discriminate responders, showing an area under the curve (AUC) of 0.756 (95% CI [0.639-0.874], p = 0.001). A further meta-analysis demonstrated the significant association of anti-CENPF levels with the patient's subsequent response to IFX, showing a standardized mean difference (SMD) of -0.65 (95% CI [-1.02;-0. 27], p = 0.018). CONCLUSIONS: Our study reveals for the first time the potential of circulating anti-CENPF antibodies to predict the clinical response to IFX before starting the treatment. This finding could be potentially useful to guide therapeutic decisions and may lead to further studies focusing on the role of CENPF on RA pathology.

Integrative Metabolic Pathway Analysis Reveals Novel Therapeutic Targets in Osteoarthritis.

In osteoarthritis (OA), impairment of cartilage regeneration can be related to a defective chondrogenic differentiation of mesenchymal stromal cells (MSCs). Therefore, understanding the proteomic- and metabolomic-associated molecular events during the chondrogenesis of MSCs could provide alternative targets for therapeutic intervention. Here, a SILAC-based proteomic analysis identified 43 proteins related with metabolic pathways whose abundance was significantly altered during the chondrogenesis of OA human bone marrow MSCs (hBMSCs). Then, the level and distribution of metabolites was analyzed in these cells and healthy controls by matrix-assisted laser desorption/ionization mass spectrometry imaging (MALDI-MSI), leading to the recognition of characteristic metabolomic profiles at the early stages of differentiation. Finally, integrative pathway analysis showed that UDP-glucuronic acid synthesis and amino sugar metabolism were downregulated in OA hBMSCs during chondrogenesis compared with healthy cells. Alterations in these metabolic pathways may disturb the production of hyaluronic acid (HA) and other relevant cartilage extracellular matrix (ECM) components. This work provides a novel integrative insight into the molecular alterations of osteoarthritic MSCs and potential therapeutic targets for OA drug development through the enhancement of chondrogenesis.

Discovery of an autoantibody signature for the early diagnosis of knee osteoarthritis: data from the Osteoarthritis Initiative.

OBJECTIVE: To find autoantibodies (AAbs) in serum that could be useful to predict incidence of radiographic knee osteoarthritis (KOA). DESIGN: A Nucleic-acid Programmable Protein Arrays (NAPPA) platform was used to screen AAbs against 2125 human proteins in sera at baseline from participants free of radiographic KOA belonging to the incidence and non-exposed subcohorts of the Osteoarthritis Initiative (OAI) who developed or not, radiographic KOA during a follow-up period of 96 months. NAPPA-ELISA were performed to analyse reactivity against methionine adenosyltransferase two beta (MAT2ß) and verify the results in 327 participants from the same subcohorts. The association of MAT2ß-AAb levels with KOA incidence was assessed by combining several robust biostatistics analysis (logistic regression, Receiver Operating Characteristic and Kaplan-Meier curves). The proposed prognostic model was replicated in samples from the progression subcohort of the OAI. RESULTS: In the screening phase, six AAbs were found significantly different at baseline in samples from incident compared with non-incident participants. In the verification phase, high levels of MAT2ß-AAb were significantly associated with the future incidence of KOA and with an earlier development of the disease. The incorporation of this AAb in a clinical model for the prognosis of incident radiographic KOA significantly improved the identification/classification of patients who will develop the disorder. The usefulness of the model to predict radiographic KOA was confirmed on a different OAI subcohort. CONCLUSIONS: The measurement of AAbs against MAT2ß in serum might be highly useful to improve the prediction of OA development, and also to estimate the time to incidence.

Analysis of Endogenous Peptides Released from Osteoarthritic Cartilage Unravels Novel Pathogenic Markers.

Osteoarthritis (OA) is a pathology characterized by the loss of articular cartilage. In this study, we performed a peptidomic strategy to identify endogenous peptides (neopeptides) that are released from human osteoarthritic tissue, which may serve as disease markers. With this aim, secretomes of osteoarthritic and healthy articular cartilages obtained from knee and hip were analyzed by shotgun peptidomics. This discovery step led to the identification of 1175 different peptides, corresponding to 101 proteins, as products of the physiological or pathological turnover of cartilage extracellular matrix. Then, a targeted multiple reaction monitoring-mass spectrometry method was developed to quantify the panel of best marker candidates on a larger set of samples (n = 62). Statistical analyses were performed to evaluate the significance of the observed differences and the ability of the neopeptides to classify the tissue. Eight of them were differentially abundant in the media from wounded zones of OA cartilage compared with the healthy tissue (p < 0.05). Three neopeptides belonging to Clusterin and one from Cartilage Oligomeric Matrix Protein showed a disease-dependent decrease specifically in hip OA, whereas two from Prolargin (PRELP) and one from Cartilage Intermediate Layer Protein 1 were significantly increased in samples from knee OA. The release of one peptide from PRELP showed the best metrics for tissue classification (AUC = 0.834). The present study reveals specific neopeptides that are differentially released from knee or hip human osteoarthritic cartilage compared with healthy tissue. This evidences the intervention of characteristic pathogenic pathways in OA and provides a novel panel of peptidic candidates for biomarker development.

Endoscopic follow-up and therapeutic attitude after ileocolonic resection in a nationwide Spanish cohort of Crohn's disease patients: the Practicrohn study.

Background: In patients with Crohn's disease (CD), endoscopic recurrence precedes clinical recurrence after ileocolonic resection. Guidelines recommend ileocolonoscopy within the first year after surgery. The study examined endoscopic monitoring and treatment decisions in CD patients in a real-world setting. Methods: The Practicrohn study involved adult patients from 26 Spanish hospitals who underwent ileocolonic resection with anastomosis from 2007 to 2010. Medical records data were collected retrospectively from diagnosis to index surgery and up to 5 years after surgery. Results: Of 314 analyzed patients, 262 (83%) underwent endoscopic evaluation, but only 30% (n = 95) had planned endoscopy as part of follow-up within the first year after surgery. An upward trend was observed in the proportion of endoscopies performed or planned within the first year after surgery across the selection period. More patients with than without endoscopic recurrence in the first year after surgery had a medication change, mainly for endoscopic activity in the absence of clinical symptoms (54 vs 13%; p = 0.02). Conclusions: Between 2007 and 2010, endoscopic monitoring of patients within the first year after CD-related surgery was less than adequate based on current standards, but showed improvement. Medication changes were in general agreement with current guideline recommendations. This work was presented as a poster (number P686) by M. Barreiro-de Acosta et al. at ECCO (European Crohn's and Colitis Organisation) '18 in Vienna, Austria, 14-17 February 2018.

Perioperative management and early complications after intestinal resection with ileocolonic anastomosis in Crohn's disease: analysis from the PRACTICROHN study.

BACKGROUND: This study is aimed at describing the prevalence of and risk factors associated with early post-operative complications after Crohn's disease-related intestinal resection. METHODS: This was a retrospective analysis of data from the PRACTICROHN cohort. Adult Crohn's disease patients who underwent ileocolonic resection with ileocolonic anastomosis between January 2007 and December 2010 were included. The complications evaluated included death, ileus, anastomotic leak, abscess, wound infection, catheter-related infection, digestive bleeding and other extra-abdominal infections that occurred in the 30 days after surgery. RESULTS: A total of 364 patients (median age at surgery 38 years and 50% men) were included. Indication for surgery was: stricturing disease (46.4%), penetrating disease (31.3%), penetrating and stricturing disease (14.0%) or resistance to medical treatment (5.8%). Early complications were recorded in 100 (27.5%) patients, with wound infection, intra-abdominal abscess and anastomotic leakage being the most frequent complications. Median hospitalization duration was 16 days for patients with complications vs. 9 days without complications (P < 0.001). Complications were more common among patients with penetrating disease (36/114, 31.6%) and those refractory to treatment (9/21, 42.9%) compared with stricturing disease (45/169, 26.6%) or stricturing + penetrating disease (6/51, 11.8%) (P = 0.040). The rate of complications was higher among patients with diagnosis made at the time of surgery (15/31, 48.4%) compared with the rest (85/331, 25.7%) (P = 0.013). Medication received at the time of surgery did not affect the rate of complications. CONCLUSIONS: Almost a quarter of patients developed early complications after intestinal resection. Penetrating disease and urgent surgery were associated with an increased risk of complications.

Alerta Rosa: Novel Alert and Navigation Breast Cancer Program in Nuevo Leon, Mexico, for Reducing Health System Interval Delays.

BACKGROUND: In Mexico, the median time between breast cancer (BC) symptom detection and treatment initiation is approximately 7 months. Alerta Rosa is a program that was developed with the intent of breaking down medical care barriers and reduce delays. PATIENTS AND METHODS: Through several media campaigns, we reached out to patients with breast symptoms or abnormal imaging studies. Patients contacted our call center or Facebook page. A navigator recorded their main complaint and scheduled a medical consultation with a specialist. We prioritized patients according to clinical risk. Those diagnosed with BC were referred to their health affiliation unit for care. RESULTS: To date, 656 patients have contacted our program. Median age was 44 years (range, 7-82). Patients reported becoming aware of Alerta Rosa mainly by word of mouth and TV. A total of 446 medical consultations were scheduled, and 309 patients attended their appointments. A biopsy procedure was solicited for 39 patients, and 22 were diagnosed with BC. Most patients had stage II (45%) or stage III (32%) disease. The median time from alert activation to treatment initiation was 33 days (range, 19-56) and from first medical evaluation to treatment initiation was 28 days (range, 16-48). CONCLUSION: In low- or middle-income countries, where BC screening programs do not effectively reach the target population, it is crucial to focus efforts in identifying and prioritizing symptomatic patients or those with abnormal imaging studies to ultimately downstage BC. Alerta Rosa proved to be successful in reducing health system intervals and could be replicated and adapted for other limited resource settings. IMPLICATIONS FOR PRACTICE: In countries such as Mexico, infrastructure and financial drawbacks limit the implementation of effective screening mammography programs. This article presents a novel and effective alternative to optimize resources and reduce health system intervals, so that patients in limited-resource settings can have access to prompt quality care. This strategy for early breast cancer detection focused efforts in prioritizing symptomatic women and those with abnormal breast imaging studies. This article presents novel information that will be useful for the development of effective early breast cancer detection with a focus on opportunistic rather than population-screening mammography in low-resource settings.

Leiomiosarcoma primario vaginal en el embarazo. A propósito de un caso / Primary vaginal leiomyosarcoma in pregnancy. About A case

RESUMEN Los sarcomas primarios de vagina son extremadamente raros especialmente durante la gestación. Se presenta el caso de una gestante de 25+2 semanas que acude a urgencias con clínica de sangrado vaginal objetivándose a la exploración una formación nodular dependiente de pared vaginal derecha. Dada la clínica se reseca en quirófano con el hallazgo histopatológico de leiomiosarcoma. A la gestante se le realiza sin incidencias una cesárea en la semana 34 de gestación, previa maduración pulmonar fetal, completándose en el puerperio inmediato el estudio de extensión sin encontrarse ningún hallazgo relevante. Finalmente, se somete a la paciente a una histerectomía y salpinguectomía bilateral con preservación ovárica. El seguimiento y los controles sucesivos de la gestante en los meses posteriores muestran ausencia de enfermedad.

ABSTRACT Primary sarcomas of the vagina are extremely rare, especially during pregnancy. We report a case of a 25-week-pregnant who came to emergency room complaining of vaginal bleeding. Pelvic examination revealed a globular mass located on the right vaginal wall. Given the persistent bleeding, resection of the mass was performed. The specimen was sent to pathology and confirmed to be a leiomyosarcoma. At 34-weeks of pregnancy after fetal lung maturation a cesarean section is done. It was completed the extension study during immediate postpartum without any relevant finding. Finally, she had a totally hysterectomy and bilateral salpingectomy with ovarian preservation. Clinical follow-up over the following months shows no evidence of disease.