Microbially induced calcium carbonate precipitation in fossil consolidation treatments: Preliminary results inducing exogenous Myxococcus xanthus bacteria in a miocene Cheirogaster richardi specimen.

This research paper proposes Microbially Induced Calcium Carbonate Precipitation (MICP) as an innovative approach for palaeontological heritage conservation, specifically on deteriorated carbonate fossils. Due to its efficiency in bioconsolidation of carbonate ornamental rocks, Myxococcus xanthus inoculation on carbonate fossils was studied in this research. Treatment was tested on nine fossil samples from decontextualized fragments of Cheirogaster richardi specimens (Can Mata site, Hostalets de Pierola, Catalonia, Spain). The main objective was to evaluate whether treatment with Myxococcus xanthus improved fossil surface cohesion and hardness and mechanical strength without significant physicochemical and aesthetic changes to the surface. Chemical compatibility of the treatment, penetration capacity and absence of noticeable changes in substrate porosity were considered as important issues to be evaluated. Samples were analysed, before and after treatment, by scanning electron microscopy, weight control, spectrophotometry, X-ray diffraction analysis, water absorption analysis, pH and conductivity control, Vickers microindentation and tape test. Results show that hardness increases by a factor of almost two. Cohesion also increases and surface disaggregated particles are bonded together by a calcium carbonate micrometric layer with no noticeable changes in surface roughness. Colour and gloss variations are negligible, and pH, conductivity and weight hardly change. Slight changes in porosity were observed but without total pore clogging. To sum up, results indicate that Myxococcus xanthus biomineralisation is an effective consolidation treatment for carbonate fossils and highly compatible with carbonate substrates. Furthermore, bacterial precipitation of calcium carbonate is a safe and eco-friendly consolidation treatment.

Phosphoproteomic analysis of neoadjuvant breast cancer suggests that increased sensitivity to paclitaxel is driven by CDK4 and filamin A.

Precision oncology research is challenging outside the contexts of oncogenic addiction and/or targeted therapies. We previously showed that phosphoproteomics is a powerful approach to reveal patient subsets of interest characterized by the activity of a few kinases where the underlying genomics is complex. Here, we conduct a phosphoproteomic screening of samples from HER2-negative female breast cancer receiving neoadjuvant paclitaxel (N = 130), aiming to find candidate biomarkers of paclitaxel sensitivity. Filtering 11 candidate biomarkers through 2 independent patient sets (N = 218) allowed the identification of a subgroup of patients characterized by high levels of CDK4 and filamin-A who had a 90% chance of achieving a pCR in response to paclitaxel. Mechanistically, CDK4 regulates filamin-A transcription, which in turn forms a complex with tubulin and CLIP-170, which elicits increased binding of paclitaxel to microtubules, microtubule acetylation and stabilization, and mitotic catastrophe. Thus, phosphoproteomics allows the identification of explainable factors for predicting response to paclitaxel.

Correlation tests between relative light unit and colony forming unit for improving adenosine triphosphate bioluminescence analysis in bacterial consolidation treatments on palaeontological heritage.

In this article bacterial carbonate mineralization treatments are proposed as a novel strategy for decayed fossils and palaeontological heritage conservation; specifically, by means of inoculation of Myxococcus xanthus, a bacterium of proven effectiveness in ornamental stone bioconsolidation. Bioconsolidation treatments can be very effective, stable, nontoxic, environmentally friendly, and chemically compatible with fossil heritage. The method reproduces what nature has been doing for millennia with fossils that have been permineralized by bacterial calcium carbonate precipitation. There is, however, some concern that bacterial inoculation could lead to the growth of undesirable microbiota, which could subsequently damage the fossil substrate. Because of this, the use of bacteria on heritage items must be meticulously monitored and analysis strategies should be carried out to detect bacteria viability during and after treatments. For this purpose, adenosine triphosphate assay is proposed in this article as a fast, affordable, portable, and easy-to-use system for conservators. as ATP assay results are relative and difficult to relate to colony forming unit, this study aims to improve their applicability by examining the correlation between ATP analysis and total viable bacteria count in the specific case of M. xanthus. This research provides reference and correlatable data to obtain an approximate estimation of M. xanthus viable bacterial colonies based on relative light unit data.

Comparison of immune activation of the COVID vaccines: ChAdOx1, BNT162b2, mRNA-1273, BBIBP-CorV, and Gam-COVID-Vac from serological human samples in Hungary showed higher protection after mRNA-based immunization.

OBJECTIVE: To gain insight into the different protective mechanisms of approved vaccines, this study focuses on the comparison of humoral and cellular immune responses of five widely used vaccines including ChAdOx1 (AZD1222, AstraZeneca), BNT162b2 (Pfizer), mRNA-1273 (Moderna), BBIBP-CorV (Sinopharm), and Gam-COVID-Vac (Sputnik V). MATERIALS AND METHODS: Isolated plasma from 95 volunteers' blood samples was used to measure anti-SARS-CoV-2 humoral and cellular immune responses. Positive controls were recovered patients from COVID-19 (unvaccinated). Specific quantification kits for anti-nucleocapsid IgG, anti-Spike protein IgG, neutralizing antibodies as well as specific SARS-CoV-2 antigens for T-cell activation were used and Spearman correlation and matrix analyses were performed to compare overall immune responses. RESULTS: Nucleocapsid antibodies were significantly higher for the BBIBP-CorV and convalescent group when compared to other vaccines. In contrast, subjects vaccinated with BNT162b2 and mRNA-1273 presented significantly higher anti-spike IgG. In fact, 9.1% of convalescent, 4.5% of Gam-COVID-Vac, 28.6% of ChAdOx1, and 12.5% of BBIBP-CorV volunteers did not generate anti-spike IgG. Similarly, a positive correlation was observed after the neutralization assay. T-cell activation studies showed that mRNA-based vaccines induced a T-cell driven immune response in all cases, while 55% of convalescents,  8% of BNT162b1,  12,5% of mRNA-1273, 9% of Gam-COVID-Vac,  57% of ChAdOx1,  and  56% of BBIBP-CorV subjects presented no cellular response. Further correlation matrix analyses indicated that anti-spike IgG and neutralizing antibodies production, and T-cell activation follow the same trend after immunization. CONCLUSIONS: RNA-based vaccines induced the most robust adaptive immune activation against SARS-CoV-2 by promoting a significantly higher T-cell response, anti-spike IgG and neutralization levels. Vector-based vaccines protected against the virus at a comparable level to convalescent patients.

Impact of ADHD symptoms on family functioning, family burden and parents’ quality of life in a hospital area in Spain

Background and objectives: The aim of this study was to evaluate whether ADHD symptom severity and ADHD subtype are associated with family functioning, family burden and quality of life, in a sample of parents of children diagnosed with ADHD.MethodsSeventy-four parents of children diagnosed with ADHD were recruited at an Outpatient Child & Adolescent Mental Health Clinic in Madrid (Spain) and afterwards completed four electronical self-administered scales to determine their perceived family functioning, family burden and quality of life, as well as the severity and subtype of ADHD symptoms in their children.ResultsSeverity of children’s ADHD symptoms negatively affected parents’ quality of life, family functioning and family burden. Higher scores in inattention and combined subtypes were correlated with lower results in those domains. In adjusted correlations, the SWAN hyperactivity/impulsivity subscale significantly correlated with the four scales.ConclusionsThese results suggest that severity of the ADHD symptoms has a negative impact on parent’s quality of life and family functioning in inattention and combined subtypes. Family therapy and other interventions targeted towards improving family relationships and caregivers’ wellbeing should be considered when managing ADHD in the clinical practice. Electronic measurement tools are a promising method of evaluation in mental health research. (AU)

Multi-centre retrospective study of the long-term outcome following suspected traumatic elbow luxation in 32 cats.

OBJECTIVES: To describe reduction techniques and clinical outcome in a series of traumatic elbow luxations in cats. MATERIALS AND METHODS: Retrospective review of unilateral elbow luxations treated at five specialist referral centres. Data included signalment, aetiology, concurrent injuries, luxation direction, time to reduction, primary reduction technique, surgical procedure and complications. Cases were excluded if reduction technique was unknown. Telephone owner questionnaire follow-up was completed using a Feline Musculoskeletal Pain Index. RESULTS: Thirty-two cats were included. Lateral luxations were most common (n = 21). Time (hours) until attempted initial closed reduction was <24 (n = 12), 24-48 (n = 13), >48 (n = 3) or unrecorded (n = 4). Luxation was treated by closed reduction alone (n = 7) or by surgery (n = 25); 14 of 25 cases underwent primary surgical reduction and 11 of 25 were secondary procedures following failure of closed reduction. Transcondylar bone tunnels and circumferential suture (n = 19) was the most commonly used surgical technique. Catastrophic (n = 1), major (n = 11) and minor complications (n = 5) were recorded; reluxation occurred more frequently after closed reduction (n = 8) than after open reduction with fixation (n = 0). Feline Musculoskeletal Pain Index data were available for 12 cats; outcome was good-excellent in all 12, with a median function score of 64.5/68 (range: 55-68) and a median pain score of 0/15 (range: 0-5). Outcome was not associated with reduction technique. CLINICAL SIGNIFICANCE: Elbow reluxation occurred in 61% of cats following primary closed reduction but did not occur in any open reduction cases. Reluxation rate increased with duration from injury. Most cats had good-excellent owner-assessed outcome, regardless of reduction technique.

The natural history of canine occult Grade II medial patellar luxation: an observational study.

OBJECTIVES: To determine the risk of lameness and the rate of subsequent medial patellar luxation surgery in dogs that present with occult Grade II medial patellar luxation. MATERIALS AND METHODS: Retrospective owner survey and review of clinical records of adult dogs diagnosed with Grade II medial patellar luxation that were initially asymptomatic and managed non-surgically that had a minimum of 4-year follow-up. Clinical notes and owner questionnaires identified dogs that subsequently developed lameness and required surgery on the previously asymptomatic stifle. RESULTS: Thirty-eight dogs were included with an average follow-up of 51 months. Seventeen dogs re-presented for unscheduled contralateral medial patellar luxation surgery at an average of 15 months after initial presentation. A further two dogs had chronic contralateral limb lameness after an average of 33 months after initial surgery and may have been potential surgical candidates. CLINICAL SIGNIFICANCE: Fifty percent of adult dogs presenting with occult Grade II medial patellar luxation subsequently developed chronic lameness or required surgery.

Utilization of naproxen by Amycolatopsis sp. Poz 14 and detection of the enzymes involved in the degradation metabolic pathway.

The pollution of aquatic environments by drugs is a problem for which scarce research has been conducted in regards of their removal. Amycolatopsis sp. Poz 14 presents the ability to biotransformation naphthalene at high efficiency, therefore, in this work this bacterium was proposed as an assimilator of naproxen and carbamazepine. Growth curves at different concentrations of naproxen and carbamazepine showed that Amycolatopsis sp. Poz 14 is able to utilize these drugs at a concentration of 50 mg L-1 as a source of carbon and energy. At higher concentrations, the bacterial growth was inhibited. The transformation kinetics of naproxen showed the total elimination of the compound in 18 days, but carbamazepine was only eliminated in 19.9%. The supplementation with cometabolites such as yeast extract and naphthalene (structure similar to naproxen) at 50 mg L-1, showed that the yeast extract shortened the naproxen elimination to 6 days and reached a higher global consumption rate compared to the naphthalene cometabolite. The biotransformation of carbamazepine was not improved by the addition of cometabolites. The partial sequencing of the genome of Amycolatopsis sp. Poz 14 detected genes encoding putative enzymes for the degradation of cyclic aromatic compounds and the activities of aromatic monooxygenase, catechol 1,2-dioxygenase and gentisate 1,2-dioxygenase exhibited their involving in the naproxen biodegradation. The HPLC-MS analysis detected the 5-methoxysalicylic acid at the end of the biotransformation kinetics. This work demonstrates that Amycolatopsis sp. Poz 14 utilizes naproxen and transforms it to 5-methoxysalicylic acid which is the initial compound for the catechol and gentisic acid metabolic pathway.

FAIRLANE, a double-blind placebo-controlled randomized phase II trial of neoadjuvant ipatasertib plus paclitaxel for early triple-negative breast cancer.

BACKGROUND: This hypothesis-generating trial evaluated neoadjuvant ipatasertib-paclitaxel for early triple-negative breast cancer (TNBC). PATIENTS AND METHODS: In this randomized phase II trial, patients with early TNBC (T ≥ 1.5 cm, N0-2) were randomized 1 : 1 to receive weekly paclitaxel 80 mg/m2 with ipatasertib 400 mg or placebo (days 1-21 every 28 days) for 12 weeks before surgery. Co-primary end points were pathologic complete response (pCR) rate (ypT0/TisN0) in the intention-to-treat (ITT) and immunohistochemistry phosphatase and tensin homolog (PTEN)-low populations. Secondary end points included pCR rate in patients with PIK3CA/AKT1/PTEN-altered tumors and pre-surgery response rates by magnetic resonance imaging (MRI). RESULTS: pCR rates with ipatasertib versus placebo were 17% versus 13%, respectively, in the ITT population (N = 151), 16% versus 13% in the immunohistochemistry PTEN-low population (N = 35), and 18% versus 12% in the PIK3CA/AKT1/PTEN-altered subgroup (N = 62). Rates of overall and complete response (CR) by MRI favored ipatasertib in all three populations (CR rate 39% versus 9% in the PIK3CA/AKT1/PTEN-altered subgroup). Ipatasertib was associated with more grade ≥3 adverse events (32% versus 16% with placebo), especially diarrhea (17% versus 1%). Higher cycle 1 day 8 (C1D8) immune score was significantly associated with better response only in placebo-treated patients. All ipatasertib-treated patients with low immune scores and a CR had PIK3CA/AKT1/PTEN-altered tumors. CONCLUSIONS: Adding ipatasertib to 12 weeks of paclitaxel for early TNBC did not clinically or statistically significantly increase pCR rate, although overall response rate by MRI was numerically higher with ipatasertib. The antitumor effect of ipatasertib was most pronounced in biomarker-selected patients. Safety was consistent with prior experience of ipatasertib-paclitaxel. A T-cell-rich environment at C1D8 had a stronger association with improved outcomes in paclitaxel-treated patients than seen for baseline tumor-infiltrating lymphocytes. This dependency may be overcome with the addition of AKT inhibition, especially in patients with PIK3CA/AKT1/PTEN-altered tumors. CLINICALTRIALS.GOV: NCT02301988.

Relationship between Tibial conformation, cage size and advancement achieved in TTA procedure.

BACKGROUND: Previous studies have suggested that there is a theoretical discrepancy between the cage size and the resultant tibial tuberosity advancement, with the cage size consistently providing less tibial tuberosity advancement than predicted. The purpose of this study was to test and quantify this in clinical cases. The hypothesis was that the advancement of the tibial tuberosity as measured by the widening of the proximal tibia at the tibial tuberosity level after a standard TTA, will be less than the cage sized used, with no particular cage size providing a relative smaller or higher under-advancement, and that the conformation of the proximal tibia will have an influence on the amount of advancement achieved. RESULTS: One hundred sixty-four dogs met the inclusion criteria. The mean percentage under-advancement was 15.5%. All dogs had an advancement less than the stated cage size inserted. An association between the proximal tibial tuberosity angle (increased in cases with low patellar tendon insertion), and percentage under-advancement was found, with an increase of 0.45% under-advancement for every 1 degree increase in angle a (p = 0.003). There was also evidence of a difference between the mean percentage under-advancement in breeds (p = 0.001) with the Labrador having the biggest under-advancement. Cage size (p = 0.83) and preoperative tibial plateau angle (p = 0.27) did not affect under-advancement. CONCLUSIONS: The conformation of the tibial tuberosity and therefore the relative cage positioning have an impact on mean percentage under-advancement of the tibial tuberosity after standard TTA. In all evaluated cases, the advancement of the tibial tuberosity was less than intended by the cage size selected.

Cáncer de metaplásico de mama: revisión de dos casos clínicos / Metaplastic breast cancer: review of two clinical cases

RESUMEN El carcinoma metaplásico de mama es un tipo de cáncer infiltrante que asemeja un carcinoma de alto grado histológico, pero cuya incidencia es muy baja (< 1%). Desde el punto de vista anatomopatológico presenta un componente mixto epitelial y mesenquimal; siendo lo más característico su comportamiento clínico altamente agresivo junto con unas características anatomopatológicas, inmunohistoquímicas concordantes, como son el HER2/neu negativo, los receptores hormonales negativos, el tamaño tumoral grande y el alto grado histológico. Por todo ello, resulta de especial interés conocer esta entidad, con la finalidad de realizar un diagnóstico preciso y llevar a cabo un tratamiento adecuado en estas pacientes. En el presente artículo se presenta la revisión de dos casos clínicos de cáncer de mama metaplásico, diagnosticados y tratados en nuestro Hospital durante el año 2015 y 2018.

ABSTRACT The metaplastic breast cancer is a subtype of an infiltranting breast cancer and it's usually high grade. However it is a rare subtype of cancer (incidence <1%). This cancer has an epithelial and connective tissues, which has an epithelial invasor ductal breast cancer with high grade and sarcomas breast. The main characteristic of the metaplastic breast cancer is their high agressive behavior as clinical as anatomopathological, which immunohistochemical expression is like a triple negative breast cancer. Because of this we consider that their knowledge is very important with the purpose of being diagnosed in women. In this paper it is showed a revision of two cases of metaplastic breast cancer, whose diagnostic and treatment were reported in our Centre.

Observation of Oscillatory Radial Electric Field Relaxation in a Helical Plasma.

Measurements of the relaxation of a zonal electrostatic potential perturbation in a nonaxisymmetric magnetically confined plasma are presented. A sudden perturbation of the plasma equilibrium is induced by the injection of a cryogenic hydrogen pellet in the TJ-II stellarator, which is observed to be followed by a damped oscillation in the electrostatic potential. The waveform of the relaxation is consistent with theoretical calculations of zonal potential relaxation in a nonaxisymmetric magnetic geometry. The turbulent transport properties of a magnetic confinement configuration are expected to depend on the features of the collisionless damping of zonal flows, of which the present Letter is the first direct observation.

Treatment of tibial diaphyseal fractures following plateless tibial tuberosity advancement to manage cranial cruciate disease.

OBJECTIVE: To report diaphyseal fractures of the proximal tibia following tibial tuberosity advancement without plate stabilisation for the management of cranial cruciate ligament rupture in dogs. METHODS: Members of the British Veterinary Orthopaedic Association's online discussion forum were invited to submit revision cases of tibial diaphyseal fracture following tibial tuberosity advancement without plate fixation. Data collected included signalment, surgical revision technique, pre- and postoperative revision radiographic findings, complications and veterinary assessment. Owners were invited to complete the Liverpool Osteoarthritis in Dogs questionnaire. RESULTS: A total of 17 dogs were included in the study. Eleven dogs had OrthoFoam-wedge modified Maquet procedures and six had the tibial tuberosity advancement rapid procedure. Tibial tuberosity advancement was maintained in 14/17 cases. Postrevision surgery complications occurred in eight cases: minor complications in 3/17 dogs; major in 5/17 and no catastrophic complications. Surgical site infection was the most common complication (4/8). Final clinical outcome found 8/17 of dogs to have excellent, 8/17 satisfactory and 1/17 poor clinical outcome. The median Liverpool Osteoarthritis in Dogs score was 12/52 (range 2 to 28). Final outcome was 6/13 owners that were very satisfied, 2/13 owners indifferent and 5/13 owners very disappointed. CLINICAL SIGNIFICANCE: This is the first case series reporting tibial diaphyseal fractures following tibial tuberosity advancement without plate stabilisation. The authors report here a wide spectrum of potential fixation strategies should one of these fractures occur.

Experiencia actual en seguimiento activo para cáncer testicular estadio I / Current experiencie in active follow-up for stage I testicular cancer

Introducción. Aproximadamente un 3% de los hombres que se han sometido a una vasectomía se realizan posteriormente una reversión de ésta con intención de fertilidad. La vasovasostomía (VV) microquirúrgica como técnica de reversión de vasectomía, permite la recanalización de los conductos deferentes, ofreciendo muy buenos resultados. Objetivo. Describir los resultados quirúrgicos y la efectividad de la VV en una serie de pacientes operados mediante una técnica simplificada. Materiales y Métodos. Estudio retrospectivo. Se analizaron antecedentes demográficos y quirúrgicos. Se utilizó una técnica de VV simplificada que consiste en realizar una miniincisión de abordaje (1 cm), sin evaluar el líquido seminal mediante la graduación de Silber y realizar la anastomosis en un plano único con material de sutura no reabsorbible 9-0. Se controló con espermiograma al primer y tercer mes post-cirugía, evaluando concentración espermática, motilidad progresiva, morfología y volumen seminal entre otros. Se calculó la tasa de permeabilidad deferencial (definida como presencia de espermatozoides en el eyaculado) y la tasa de embarazo post VV. Resultados. Un total de 75 pacientes fueron incluidos en el estudio, operados entre agosto de 2009 y julio de 2016 por 2 cirujanos (CP, MM). La edad media (± desviación estándar) de los pacientes y de sus parejas fue de 43,9 ± 6,4 años y 34,4 ± 4,2 años, respectivamente. La mediana del tiempo transcurrido entre la vasectomía y la VV fue de 8 años (2 ­ 21 años). La mediana del tiempo quirúrgico fue de 110 minutos (85 ­ 183 minutos), con menos de un 3 por ciento de complicaciones post-operatorias (todas grado-I según escala Clavien-Dindo). Al primer mes el 93 por ciento de los pacientes tenía espermatozoides en el eyaculado, con una mediana de concentración de 12 x 10

Introducción. Stage I testicular cancer represents the most usual presentation of this disease. Adjuvant therapy (chemotherapy, radiotherapy, surgery) or active surveillance (AS) have been in constant evaluation in the last years. AS has proven to be an excellent treatment option, given its high rates of cancer specific survival. The objective of this study is to evaluate the local experience with stage I testicular cancer patients. Materials y Methods. Retrospective study of 124 patients with testicular cancer in a 5 year lapse. Data of histologic risk factors for progression, disease progression/recurrence, elected treatment and compliance to follow up were recorded. Results. Data was analysed for 97 stage I testicular cancer. 46 out of these patients were submitted to active surveillance. Histologic risk factors from pure seminoma and non seminoma were compared separately. Statistic difference was demonstrated in patients elected to active treatment with rete testis invasion (p: 0.02). No difference was demonstrated in risk factors for non seminoma. Compliance to maintain follow up in the AS group was 57 pertcent. Conclusion: Active surveillance is a valid option of treatment. In our center, this treatment option was associated with low adherence to follow up, which could imply negative consequences to the patients over time. Histologic risk factors are not exclusive factors for the decision of treatment in these patients. (AU)

Multi-centre retrospective study of long-term outcomes following traumatic elbow luxation in 37 dogs.

OBJECTIVES: Limited guidelines exist regarding the optimal treatment of traumatic canine elbow luxation, and there is a lack of information on long-term functional outcome. Here we report reduction and stabilisation techniques for a series of traumatic elbow luxations and describe clinical outcome plus long-term questionnaire-based follow-up. METHODS: Retrospective review of canine traumatic elbow luxations (2006 to 2013) treated at five referral centres. Data recorded included signalment, luxation aetiology, time to reduction, reduction technique, surgical procedure, post-reduction care and complications. Questionnaire follow-up was attempted for all cases with owners completing the Canine Brief Pain Inventory. RESULTS: Thirty-seven dogs were included. The most frequent cause of luxation was road traffic accident (n=22). Twenty cases were treated surgically. Seven dogs suffered major postoperative complications: reluxation (n=6), infection requiring implant removal (n=1). Four of the six reluxations occurred in dogs that had other orthopaedic injuries. Twenty-two owners completed the Canine Brief Pain Inventory questionnaire: there were 13 excellent, 6 very good, 1 good and 2 fair outcomes. Outcome was not associated with the reduction technique. CLINICAL SIGNIFICANCE: Initial closed reduction, followed by surgical stabilisation if unsuccessful, results in good-to-excellent outcomes in the majority of traumatic canine elbow luxations. Reluxation was the most common major complication and there was a higher incidence of reluxation in patients with multiple orthopaedic injuries.

Recomendaciones para el uso de metotrexato en pacientes con artritis idiopática juvenil / Recommendations for the use of methotrexate in patients with juvenile idiopathic arthritis

OBJETIVOS: Elaborar un documento de recomendaciones consensuadas para el uso de metotrexato (MTX) en pacientes con artritis idiopática juvenil (AIJ). MATERIAL Y MÉTODO: Un grupo de 11 expertos planteó diversos interrogantes clínicos en el uso de MTX en pacientes con AIJ. Se realizó una revisión sistemática y se extrajeron las evidencias y recomendaciones para cada pregunta. Los resultados fueron valorados y consensuados por los expertos en una sesión presencial para establecer las recomendaciones finales. RESULTADOS: Se recomienda el MTX como primer fármaco inductor de remisión en AIJ, cuya indicación se realizará según la categoría clínica del paciente. Previo al tratamiento se recomienda evaluar un hemograma que incluya recuento leucocitario, niveles de enzimas hepáticas y creatinina sérica, así como otros parámetros analíticos conforme a factores de riesgo específicos. El tratamiento se iniciará con dosis de 10-15mg/m2/semana. En casos de uveítis o poliartritis se valorará una dosis inicial de 15mg/m2/semana. Para una mejor biodisponibilidad y tolerabilidad, se administrará preferentemente por vía parenteral si la dosis es≥15mg/m2/semana. Se deberá realizar un seguimiento analítico del paciente periódicamente y evaluar posibles alteraciones en enzimas hepáticas para realizar cambios si fuera preciso. La combinación con biológicos puede ser necesaria, además del uso concomitante de ácido fólico o folínico. CONCLUSIONES: Este documento recoge las principales recomendaciones para el empleo adecuado de MTX en pacientes con AIJ, de acuerdo a la evidencia científica y a la experiencia clínica

OBJECTIVES: To develop a consensus document of recommendations for the use of methotrexate (MTX) in patients with juvenile idiopathic arthritis (JIA). MATERIAL AND METHOD: A group of eleven experts proposed several clinical questions on the use of MTX in patients with JIA. A systematic review was conducted and the evidence and recommendations for each question were extracted. The results were discussed and validated by the experts in a work session to establish the final recommendations. RESULTS: MTX is recommended as the first drug for inducing remission in JIA, and its indication should be made according to the clinical category of the patient. Prior to treatment, it is recommended to perform a complete blood count, including white cells, levels of liver enzymes, serum creatinine, and other analytical parameters according to specific risk factors. Treatment should be initiated with a dose of 10-15mg/m2/week. In cases of uveitis or polyarthritis, an initial dose of 15mg/m2/week should be considered. For a better bioavailability and tolerability, it is preferable to administer MTX parenterally if the dose is ≥15mg/m2/week. It is necessary to periodically perform an analytical monitoring of the patient and to assess possible alterations in liver enzymes to make changes if necessary. Combinations with biological agents may be necessary, as well as the concomitant addition of folic or folinic acid. CONCLUSIONS: This document describes the main recommendations for the appropriate use of MTX in JIA patients, according to scientific evidence and clinical experience

[Recommendations for the use of methotrexate in patients with juvenile idiopathic arthritis]. / Recomendaciones para el uso de metotrexato en pacientes con artritis idiopática juvenil.

OBJECTIVES: To develop a consensus document of recommendations for the use of methotrexate (MTX) in patients with juvenile idiopathic arthritis (JIA). MATERIAL AND METHOD: A group of eleven experts proposed several clinical questions on the use of MTX in patients with JIA. A systematic review was conducted and the evidence and recommendations for each question were extracted. The results were discussed and validated by the experts in a work session to establish the final recommendations. RESULTS: MTX is recommended as the first drug for inducing remission in JIA, and its indication should be made according to the clinical category of the patient. Prior to treatment, it is recommended to perform a complete blood count, including white cells, levels of liver enzymes, serum creatinine, and other analytical parameters according to specific risk factors. Treatment should be initiated with a dose of 10-15 mg/m(2)/week. In cases of uveitis or polyarthritis, an initial dose of 15 mg/m(2)/week should be considered. For a better bioavailability and tolerability, it is preferable to administer MTX parenterally if the dose is ≥15 mg/m(2)/week. It is necessary to periodically perform an analytical monitoring of the patient and to assess possible alterations in liver enzymes to make changes if necessary. Combinations with biological agents may be necessary, as well as the concomitant addition of folic or folinic acid. CONCLUSIONS: This document describes the main recommendations for the appropriate use of MTX in JIA patients, according to scientific evidence and clinical experience.

Use of bevacizumab as a first-line treatment for metastatic breast cancer.

OBJECTIVE: During clinical practice, it can be challenging, given the lack of response biomarkers, to identify the patients with metastatic breast cancer (mbca) who would benefit most from the addition of bevacizumab to first-line standard chemotherapy. The aim of the present review was to summarize the relevant scientific evidence and to discuss the experience of a group of experts in using bevacizumab to treat mbca. METHODS: A panel of 17 Spanish oncology experts met to discuss the literature and their experience in the use of bevacizumab as first-line treatment for mbca. During the meeting, discussions focused on three main issues: the profile of the patients who could benefit most from bevacizumab, the optimal bevacizumab treatment duration, and the safety profile of bevacizumab. RESULTS: The subset of mbca patients who would benefit the most from the addition of bevacizumab to first-line standard chemotherapy are those with clinically defined aggressive disease. Treatment with bevacizumab should be maintained until disease progression or the appearance of unacceptable toxicity. In the mbca setting, the toxicity profile of bevacizumab is well known and can be managed in clinical practice after adequate training. CONCLUSIONS: This expert group recommends administering bevacizumab as first-line treatment in patients with clinically aggressive disease.

Perioperative risk factors for surgical site infection in tibial tuberosity advancement: 224 stifles.

OBJECTIVE: To examine perioperative factors affecting surgical site infection (SSI) rate following tibial tuberosity advancement (TTA). STUDY DESIGN: Retrospective case series. SAMPLE POPULATION: 224 stifles in 186 dogs. METHODS: Medical records of dogs that underwent TTA in a single institution were reviewed. Information on signalment, anaesthetic and surgical parameters, as well as occurrence of SSI was recorded. Dogs were followed for a minimum of three months postoperatively. The association between perioperative factors and SSI was assessed using Chi-squared tests and binary logistic regression. RESULTS: The prevalence of SSI was 5.3% (12/224 TTA). Surgical time (p = 0.02) and anaesthesia time (p = 0.03) were significantly associated with SSI. For every minute increase in surgical time and anaesthesia time, the likelihood of developing SSI increased by seven percent and four percent respectively. The use of postoperative antimicrobial therapy was not significantly associated with lower SSI (p = 0.719). Implants were removed in 1.3% of cases (3/224 TTA). CONCLUSIONS: The findings of this study suggest that increased surgical and anaesthesia times are significant risk factors for SSI in TTA, and that there is no evidence that postoperative prophylactic antimicrobial therapy is associated with SSI rate.

Risk factors for tibial tuberosity fracture after tibial tuberosity advancement in dogs.

OBJECTIVE: To retrospectively identify factors that predispose to tibial tuberosity (TT) fracture after tibial tuberosity advancement (TTA) in dogs. METHODS: The medical records and radiographs of a group of control dogs (n = 212) that had TTA surgery (n = 241 procedures) and did not sustain a fracture between 2008 and 2013, and those of 12 dogs that did sustain a fracture (n = 13 procedures) between 2008 and 2013 at two veterinary teaching hospitals were evaluated to determine the effect of signalment, body weight and surgical inaccuracies on TT fracture. Multivariable logistic regression was performed with the occurrence of TT fracture as the outcome variable of interest. RESULTS: Signalment and body weight were not found to be associated with TT fracture. Of the surgical inaccuracies, osteotomy shape (p = 0.003), plate position (p = 0.009), and cage position (p = 0.039) were factors significantly associated with TT fracture. CLINICAL SIGNIFICANCE: This study provides data to support the hypothesis that poor plate position, poor cage position, and narrow distal osteotomy width are associated with TT fracture after TTA. We conclude that it is of paramount importance to pay careful attention to surgical technique in order to reduce this risk.