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This case series aims to characterize the development of systemic lupus erythematosus (SLE) induced by anti-tumor necrosis factor α (anti-TNFα) therapy in patients with inflammatory rheumatic diseases, namely rheumatoid arthritis (RA), spondylarthritis (SpA), and psoriatic arthritis (PsA). Patients with a diagnosis of SLE induced by anti-TNFα therapy and registered on the Rheumatic Diseases Portuguese Register (Reuma.pt) who started their first anti-TNFα between 2001 and 2020 were included. Demographic, clinical, and laboratory data were obtained by consulting Reuma.pt. The diagnosis of SLE induced by anti-TNFα was considered if there was a temporal relationship between the onset of anti-TNFα therapy and manifestations (clinical and immunological) in accordance with the American College of Rheumatology/European League Against Rheumatism criteria (2019). A total of 607 patients with inflammatory rheumatic diseases and six cases of SLE induced by anti-TNF-α therapy were reviewed: two patients were affected by RA, three patients by SpA, and one by PsA. All these patients had articular and constitutional symptoms that improved after discontinuation of the anti-TNFα agent. After switching to a second anti-TNFα agent, there was no recurrence of SLE over time. The development of SLE secondary to anti-TNFα agents in inflammatory rheumatic patients is rare. In this case series, all patients had a mild disease that improved after therapy discontinuation without recurrence of the disease. SLE induced by anti-TNFα should be considered in the follow-up of RA, SpA, and PsA patients.

ABSTRACT The aim of this study was to evaluate the yield, the morphometric characteristics, and the nutritional value of corn with use of foliar fungicide associated with inoculant on ensiling on the chemical-fermentative characteristics of silage. The applications of fungicide pyraclostrobin + fluxpyroxade were carried out in vegetative-eight and tasseling stage, and the evaluations of plants occurred simultaneously at harvest (dough grain stage), during which application was made with inoculant consisting of strains of Lactobacillus buchneri and L. casei for silage production. The use of fungicide decreased the percentage of leaf area affected by Diplodia macrospora Earle, Cercospora zeae-maydis and Phaeosphaeria maydis. At harvest, corn showed fewer dry leaves and higher yields of fresh (66,368vs. 62,015kg·ha-1) and dry biomass (20,964 vs. 19,485kg·ha-1) with fungicide. The fungicide also reduced the LDA content from 5.99% to 5.16%, which generated greater ISDMD for whole plant (43.14 and 62.57%, for 24 and 48 hours, respectively). The association of fungicide with inoculant promoted higher concentration of acetic acid than when each was used alone, and the dry matter losses of silage with inoculant were higher than control silage (8.88vs. 12.78%, respectively). Fungicide and inoculant used in combination provided silages with lower fibrous content.

The last consensus statement of the Spanish Society of Neurology’s Demyelinating Diseases Study Group on the treatment of multiple sclerosis (MS) was issued in 2016. Although many of the positions taken remain valid, there have been significant changes in the management and treatment of MS, both due to the approval of new drugs with different action mechanisms and due to the evolution of previously fixed concepts. This has enabled new approaches to specific situations such as pregnancy and vaccination, and the inclusion of new variables in clinical decision-making, such as the early use of high-efficacy disease-modifying therapies (DMT), consideration of the patient’s perspective, and the use of such novel technologies as remote monitoring.In the light of these changes, this updated consensus statement, developed according to the Delphi method, seeks to reflect the new paradigm in the management of patients with MS, based on the available scientific evidence and the clinical expertise of the participants.The most significant recommendations are that immunomodulatory DMT be started in patients with radiologically isolated syndrome with persistent radiological activity, that patient perspectives be considered, and that the term “lines of therapy” no longer be used in the classification of DMTs (> 90% consensus). Following diagnosis of MS, the first DMT should be selected according to the presence/absence of factors of poor prognosis (whether epidemiological, clinical, radiological, or biomarkers) for the occurrence of new relapses or progression of disability; high-efficacy DMTs may be considered from disease onset. Resumen: El último documento de consenso del Grupo de Estudio de Enfermedades Desmielinizantes de la Sociedad Española de Neurología sobre el tratamiento de la esclerosis múltiple (EM) data del año 2016. Aunque muchas consideraciones continúan todavía vigentes, desde entonces se han producido significativos cambios en el manejo y tratamiento de esta enfermedad motivados no sólo por la aprobación de nuevos fármacos con diferentes mecanismos de acción, sino también por la evolución de conceptos otrora consolidados. Esto ha permitido abordar situaciones especiales como el embarazo y la vacunación desde otra perspectiva e incluir nuevas variables en la toma de decisiones en práctica clínica, como plantear tratamiento modificador de la enfermedad (TME) de alta eficacia en fases tempranas, considerar la perspectiva del paciente y utilizar nuevas tecnologías como monitorización remota.Estos cambios han motivado la presente actualización del consenso mediante metodología Delphi, con el objetivo de reflejar el nuevo paradigma de manejo del paciente con EM basándose en la evidencia científica y experiencia clínica de los participantes.Entre las principales conclusiones destacan como recomendaciones: iniciar TME inmunomodulador en el síndrome radiológico aislado con actividad radiológica persistente, evaluar la perspectiva del paciente y abandonar la terminología “líneas de tratamiento” en la clasificación de los TME (consenso mayor del 90%). Tras el diagnóstico de EM, la elección del primer TME debería considerar la presencia/ausencia de factores de mal pronóstico (epidemiológicos, clínicos, radiológicos y biomarcadores) para la aparición de nuevos brotes o progresión de discapacidad, pudiendo plantear desde el inicio TME de alta eficacia.

Resumen: El último documento de consenso del Grupo de Estudio de Enfermedades Desmielinizantes de la Sociedad Española de Neurología sobre el tratamiento de la esclerosis múltiple (EM) data del año 2016. Aunque muchas consideraciones continúan todavía vigentes, desde entonces se han producido cambios significativos en el manejo y tratamiento de esta enfermedad, motivados no solo por la aprobación de nuevos fármacos con diferentes mecanismos de acción, sino también por la evolución de conceptos otrora consolidados. Esto ha permitido abordar situaciones especiales como el embarazo y la vacunación desde otra perspectiva, e incluir nuevas variables en la toma de decisiones en práctica clínica, como plantear tratamiento modificador de la enfermedad (TME) de alta eficacia en fases tempranas, considerar la perspectiva del paciente y utilizar nuevas tecnologías como monitorización remota.Estos cambios han motivado la presente actualización del consenso mediante metodología Delphi, con el objetivo de reflejar el nuevo paradigma de manejo del paciente con EM basándose en la evidencia científica y la experiencia clínica de los participantes.Entre las principales conclusiones destacan como recomendaciones: iniciar TME inmunomodulador en el síndrome radiológico aislado con actividad radiológica persistente, evaluar la perspectiva del paciente y abandonar la terminología «líneas de tratamiento» en la clasificación de los TME (consenso mayor del 90%). Tras el diagnóstico de EM la elección del primer TME debería considerar la presencia/ausencia de factores de mal pronóstico (epidemiológicos, clínicos, radiológicos y biomarcadores) para la aparición de nuevos brotes o progresión de discapacidad, pudiendo plantear desde el inicio TME de alta eficacia. Abstract: The last consensus statement of the Spanish Society of Neurology's Demyelinating Diseases Study Group on the treatment of multiple sclerosis (MS) was issued in 2016. Although many of the positions taken remain valid, there have been significant changes in the management and treatment of MS, both due to the approval of new drugs with different action mechanisms and due to the evolution of previously fixed concepts. This has enabled new approaches to specific situations such as pregnancy and vaccination, and the inclusion of new variables in clinical decision-making, such as the early use of high-efficacy disease-modifying therapies (DMT), consideration of the patient's perspective, and the use of such novel technologies as remote monitoring.In the light of these changes, this updated consensus statement, developed according to the Delphi method, seeks to reflect the new paradigm in the management of patients with MS, based on the available scientific evidence and the clinical expertise of the participants.The most significant recommendations are that immunomodulatory DMT be started in patients with radiologically isolated syndrome with persistent radiological activity, that patient perspectives be considered, and that the term “lines of therapy” no longer be used in the classification of DMTs (> 90% consensus). Following diagnosis of MS, the first DMT should be selected according to the presence/absence of factors of poor prognosis (whether epidemiological, clinical, radiological, or biomarkers) for the occurrence of new relapses or progression of disability; high-efficacy DMTs may be considered from disease onset.

ABSTRACT This study aimed to evaluate the forage yield, morphology, and nutritional value of three winter cereal wheat (Triticum aestivum cv. BRS Umbu), white oats (Avena sativa cv. URS Guará), and black oats (Avena strigosa cv. Embrapa 139), harvested in two successive cuts, at the vegetative and full vegetative stages, applied or not with fungicide pyraclostrobin. Pyraclostrobin was sprayed two times during the vegetative stage, the first application at the phenological stage V5, and the second, 12 days after the first cut of each forage species. In general, the application of pyraclostrobin resulted in an increase in the participation of leaves in the plant structure, from 72.2% to 86.9% in the second cut; and crude protein increased, and lignin decreased (from 22.75% and 9.89% to 25.60% and 6.30%, respectively) in the first cut and (from 20.82% and 11.73% to 22.28% and 9.20%, respectively) in the second cut. Black and white oats had a higher cumulative biomass production, 3,698 kg ha-1, and 3,277kg ha-1, respectively, and white oats had the lowest content of acid detergent fiber (27.90%) at the second cut.

Abstract Human and veterinary medicine have historically presented many medical areas of potential synergy and convergence. Mechanical osteoarthritis (MOA) is characterized by a gradual complex imbalance between cartilage production, loss, and derangement. Any joint instability that results in an abnormal overload of the joint surface can trigger MOA. As MOA has a prevailing mechanical aetiology, treatment effectiveness can only be accomplished if altered joint mechanics and mechanosensitive pathways are normalized and restored. Otherwise, the inflammatory cascade of osteoarthritis will be initiated, and the changes may become irreversible. The management of the disease using non-steroidal anti-inflammatory drugs, analgesics, physical therapy, diet changes, or nutraceuticals is conservative and less effective. MOA is a determinant factor for the development of hip dysplasia in both humans and dogs. Hip dysplasia is a hereditary disease with a high incidence and, therefore, of great clinical importance due to the associated discomfort and significant functional limitations. Furthermore, on account of analogous human and canine hip dysplasia disease and under the One Medicine concept, unifying veterinary and human research could improve the well-being and health of both species, increasing the acknowledgement of shared diseases. Great success has been accomplished in humans regarding preventive conservative management of hip dysplasia and following One Medicine concept, similar measures would benefit dogs. Moreover, animal models have long been used to better understand the different diseases’ mechanisms. Current research in animal models was addressed and the role of rabbit models in pathophysiologic studies and of the dog as a spontaneous animal model were highlighted, denoting the inexistence of rabbit functional models to investigate therapeutic approaches in hip MOA.

Spontaneous subcapsular and perirenal hemorrhage, known as Wunderlich syndrome (WS), is a rare clinical manifestation of polyarteritis nodosa (PAN). We report a case of a 48-year-old male with a history of recurrent episodes of leg muscle tenderness and dysesthesia, bilateral flank pain, painful nodular skin lesions in the lower limbs, weight loss, and difficult-to-control arterial hypertension. The abdominopelvic computed tomography angiography showed a large left perirenal hematoma, leading to the patient’s admission to the intensive care unit. After the exclusion of infectious or neoplastic foci, the patient was diagnosed with PAN and started intravenous methylprednisolone pulses with a good response. Since WS is a rare initial clinical manifestation of PAN, an early diagnosis and aggressive treatment will significantly improve clinical outcomes.

Introduction and objective: Teriflunomide is an oral immunomodulatory agent approved for the treatment of relapsing–remitting multiple sclerosis (RRMS). We examined teriflunomide outcomes in patients with RRMS under clinical practice conditions in Spain. Material and methods: Non-interventional, retrospective study at 15 sites in the Autonomous Region of Madrid and nearby regions. Effectiveness (relapses, EDSS, gadolinium-enhancing T1 lesions and new/enlarged T2-weighted lesions), safety (adverse events), and reasons for discontinuation during the 24 months after teriflunomide initiation were reported. Results: A total of 776 patients were included (mean [SD] age was 43.3 (9.8) years; 69.3% were female). Two-thirds (67.7%) of patients had received a prior treatment, with beta-interferons or glatiramer acetate (BRACE) as the most frequent (93.5%) treatment. After 24 months, teriflunomide significantly reduced the annualized relapse rate (ARR) by 72% (mean [95% confidence interval] 0.12 [0.10, 0.14] vs 0.43 [0.40, 0.47] at baseline; P

Behçet disease (BD) is a rare systemic vasculitis of unknown etiology, primarily characterized by recurrent oral aphthous ulcers, genital ulcers, uveitis, and skin lesions. Pathergy test positivity is a nonspecific inflammatory response of the skin to trauma and supports the diagnosis. Recently, new inducers of pathergy reactions have been identified, for example, the placement of dental braces and laser hair removal. Our clinical case highlights the importance of thinking about this potential pathergy inducer in BD patients, to improve their quality of life and avoid complications.

Background: Standard criteria for defining suboptimal response to disease-modifying treatment (DMT) in patients with multiple sclerosis (MS) are lacking. Decision-making on how and when DMTs should be switched is challenging. The objective of the study was to identify areas of agreement on which and when specific assessments should be conducted to monitor patient response to DMT. Methods: A survey comprising 54 statements in nine categories was drafted by eight MS experts after gathering insight during four previous meetings of a total of 25 MS experts. For each statement, results were classified as being in general agreement (≥66.6% responded “Strongly agree” or “Agree”) or general disagreement (≥66.6% responded “Strongly disagree” or “Disagree”). Results: The survey was sent to 790 MS neurologists, 151 of whom participated (19%), and 98 (65%) completed it. General agreement and disagreement were reached for 45 and 2 statements, respectively, on different aspects of MS management, including treatment response, MS relapses, progression, disease activity measured by imaging and biomarkers, neuropsychological evaluation, brain volume loss, DMT switches due to lack of response and applicability to clinical practice. Conclusions: This study aims to provide guidance for the early identification of suboptimal response to DMT and for improving MS patient monitoring and treatment.

Introduction Substance use disorders(SUDs) are a major health concern and current treatment interventions have proven only limited success. Despite increasing effectiveness, still about 50–60% relapse within 6–12 months after treatment [Cornelius et al., Addict Behav. 2003;28 381-386]. SUDs are defined as chronic disorders of brain reward system, motivation, and memory processes that have gone awry. Medication reducing craving and substance use is mainly available for alcohol dependence and to a lesser extent for other substances. Hallucinogens may represent a group of agents with potential anti-craving properties subsequently reducing substance use in SUD patients. For instance, lysergic acid diethylamide(LSD) and psilocybin have previously been shown to effectively alleviate symptoms of alcohol and nicotine dependence. Objectives New treatments preferably focusing on reducing craving and subsequent substance use are therefore urgently needed. The hallucinogen psilocybin may provide a new treatment option for SUD patients, given the beneficial results observed in recent studies Methods Systematic revision of literature. Results In the 1950s, a group of drugs with potential to alter consciousness were discovered (hallucinogens). Several studies suggested their anti-SUD potential, improving self-acceptance and interpersonal relationships, reducing craving and alcohol use. As a result of its recreational popularity during the 1960s, they were banned in 1967, greatly hampering scientific research in this field. Recently, psilocybin, an hallucinogenic substance in psilocybin-containing mushrooms has gained popularity in neuropsychological research, showing to increase trait openness, cognitive and behavioral flexibility, and ratings of positive attitude, mood, social effects, and behavior and even reported persistent positive changes in attitude and behavior. These findings might suggest a valuable compound for the treatment of psychiatric conditions with several additional studies providing supportive evidence for the therapeutic potential of psilocybin for SUD treatment and relapse prevention. Conclusions With the reported limited amount of side effects and potential beneficial effects of psilocybin in SUD, there are valid reasons to further investigate the therapeutic efficacy and safety of psilocybin as a potential SUD treatment. On the one hand, psilocybin may exert its anti-addictive properties by beneficial effects on negative emotional states and stress. On the other hand, psilocybin may improve cognitive inflexibility and compulsivity. Research on the efficacy of psilocybin on SUD is still limited to a handful of published studies to date. As a result, many important questions related to the use of psilocybin as a complement to current treatment of SUD and its working mechanisms remain unanswered. Before psilocybin can be implemented as a treatment option for SUD, more extensive research is needed. Disclosure of Interest None Declared

Rheumatic musculoskeletal diseases or RMD [rheumatoid arthritis (RA) and spondyloarthritis (SpA)] are systemic inflammatory diseases for which there are no biomarkers capable of predicting treatments with a higher likelihood of response in naive patients. In addition, the expiration of the anti-TNF blocking drugs’ patents has resulted in the availability of anti-TNF biosimilar drugs with the same efficacy and safety than originators but at significantly reduced prices. To guarantee a personalized therapeutic approach to RMD treatment, a board of rheumatologists and stakeholders from the Campania region, Italy, developed a clinically applicable arthritis therapeutic algorithm to guide rheumatologists (DATA project). The general methodology relied on a Delphi technique forecast to produce a set of statements that summarized the experts’ consensus. Selected clinical scenarios were discussed in light of the available evidence, and there were two rounds of voting on the therapeutic approaches. Separate discussions were held regarding rheumatoid arthritis, psoriatic arthritis, and ankylosing spondylitis. The decision-making factors for each disease were clinical presentation, demographics, and comorbidities. In this paper, we describe a virtuous process between rheumatologists and healthcare system stakeholders that resulted in the development of a shared therapeutic algorithm for RMD patients naive to bDMARDs.

ABSTRACT The aim of this study was to evaluate the yield, morphometric and chemical characteristics, and the digestibility of various corn hybrids cultivated in different locations for silage production. Four corn hybrids were grown: P2866H, P3456H, P30R50VYH and P4285YHR, in four locations, defined as farm A; B; C and D. The hybrid P4285YHR presented the highest plant and ear insertion heights (2.72m, 1.52m respectively), with a minimum registered height of 2.63 m and 1.42 m, for plant and ear insertion height, and for that reason it presented the highest yield of fresh biomass (78,089kg ha-1). The TND values showed trend very close to that observed in the DISMS of the whole-plant, with hybrid P3456H presenting the highest estimated value (68.74%), and the hybrid P4285YHR the lowest among them (65.25%). In general, lower fibrous carbohydrates and lignin content, higher fibrous carbohydrates content, together with satisfactory grains participation in the plant structure led to a greater dry matter digestibility. Hybrids with lower plant heights do not necessarily have lower dry biomass yields, but hybrids of greater height and with high stem and leaf participation tend to have a higher aFDN content and less dry matter digestibility.

The primary objectives of the study were to evaluate the efficacy and safety of tofacitinib and baricitinib up to 24 months of follow-up in patients with rheumatoid arthritis (RA) treated in Southern Italy. Patients’ data, activity index, and clinimetric scores were collected at baseline (T0), six (T6), twelve (T12), and twenty-four (T24) months following treatment initiation. At six, twelve, and twenty-four months, adverse events and treatment cessation were also recorded. Sixty-eight patients (mean age: 62.2±10.9 years; mean RA duration: 15±9.6 years) were enrolled over a period of 12 weeks. At baseline, twenty-four patients (35.3%) were treated with tofacitinib, and forty-four patients (64.7%) were treated with baricitinib. The baseline mean disease activity was moderate as measured by DAS28- ESR (5.0±1.0), DAS 28 CRP (4.69±0.94), and SDAI (26.87±10.73) score. Before beginning JAKinhibs therapy, thirty-two patients (61.8%) were taking bDMARDs, while the remaining thirty-six (38.2%) were bDMARDs-naïve. The 24-month retention rate for JAKinhibs was 91.1%. Six months after beginning treatment with JAKinhibs, a statistically significant improvement was observed in all evaluated activity indices and clinimetric scores. Improvement was confirmed during the 12- and 24-month follow-up evaluations. The positive correlation between baseline-T6 SDAI delta and discontinuation of JAKinhibs (p=0.02) suggests that RA worsening in the first six months may be a predictor of therapy withdrawal. Patients with RA responded favorably to tofacitinib and baricitinib in this prospective, real-world study from a single center in Southern Italy. Efficacy was observed despite an underlying persistent and treatment-resistant disease.

Resumen: Antecedentes: La reciente aparición de terapias de alta efectividad para el tratamiento de la esclerosis múltiple (EM), con potencial riesgo de complicaciones infecciosas, obliga plantear estrategias de prevención y minimización de riesgos. La vacunación constituye una parte esencial del manejo de estos pacientes. Este consenso recoge una serie de pautas y escenarios prácticos de vacunación en pacientes adultos con EM candidatos a tratamiento inmunosupresor. Metodología: Se llevó a cabo un consenso de tipo formal. Tras definir el alcance del documento, se realizó una búsqueda bibliográfica de vacunación en pacientes con EM, así como guías de vacunación específicas de pacientes inmunosuprimidos y en tratamiento biológico con otras enfermedades. Para la formulación de las recomendaciones se empleó la metodología de Modified Nominal Group Technique. Desarrollo: La vacunación en pacientes candidatos a tratamiento inmunosupresor se debe plantear antes de iniciar un tratamiento inmunosupresor siempre que la situación clínica del paciente lo permita. Se recomendarán tanto aquellas indicadas en el calendario vacunal del adulto, como algunas específicas, en función de la inmunidad previa. Si ya está instaurado el tratamiento inmunosupresor las vacunas vivas atenuadas estarán contraindicadas. Para aquellas vacunas que dispongan de un correlato de protección se recomienda monitorizar la respuesta serológica transcurridos de uno a 2 meses de la última dosis. Abstract: Background: The recent development of highly effective treatments for multiple sclerosis (MS) and the potential risk of infectious complications require the development of prevention and risk minimisation strategies. Vaccination is an essential element of the management of these patients. This consensus statement includes a series of recommendations and practical scenarios for the vaccination of adult patients with MS who are eligible for highly effective immunosuppressive treatments. Methodology: A formal consensus procedure was followed. Having defined the scope of the statement, we conducted a literature search on recommendations for the vaccination of patients with MS and specific vaccination guidelines for immunosuppressed patients receiving biological therapy for other conditions. The modified nominal group technique methodology was used to formulate the recommendations. Development: Vaccination in patients who are candidates for immunosuppressive therapy should be considered before starting immunosuppressive treatment providing the patient's clinical situation allows. Vaccines included in the routine adult vaccination schedule, as well as some specific ones, are recommended depending on the pre-existing immunity status. If immunosuppressive treatment is already established, live attenuated vaccines are contraindicated. For vaccines with a correlate of protection, it is recommended to monitor the serological response in an optimal interval of 1-2 months from the last dose.

Background: The recent development of highly effective treatments for multiple sclerosis (MS) and the potential risk of infectious complications require the development of prevention and risk minimisation strategies. Vaccination is an essential element of the management of these patients. This consensus statement includes a series of recommendations and practical scenarios for the vaccination of adult patients with MS who are eligible for highly effective immunosuppressive treatments. Methodology: A formal consensus procedure was followed. Having defined the scope of the statement, we conducted a literature search on recommendations for the vaccination of patients with MS and specific vaccination guidelines for immunosuppressed patients receiving biological therapy for other conditions. The modified nominal group technique methodology was used to formulate the recommendations. Development: Vaccination should be considered in patients eligible for immunosuppressive therapy before the treatment is started, if the patient’s clinical situation allows it. We recommend administering the vaccines included in the adult vaccination calendar and some specific vaccines, depending on the patient’s pre-existing immune status. Live attenuated vaccines are contraindicated when immunosuppressive treatment has already started. For vaccines providing a correlate of protection, serological response should be monitored after an interval of 1–2 months after the last dose. Resumen: Antecedentes: La reciente aparición de tratamientos de alta efectividad para el tratamiento de la Esclerosis Múltiple (EM) con potencial riesgo de complicaciones infecciosas obliga plantear estrategias de prevención y minimización de riesgos. La vacunación constituye una parte esencial del manejo de estos pacientes. Este consenso recoge una serie de pautas y escenarios prácticos de vacunación en pacientes adultos con EM candidatos a tratamiento inmunosupresor. Metodología: Se llevó a cabo un consenso de tipo formal. Tras definir el alcance del documento, se realizó una búsqueda bibliográfica de vacunación en pacientes con EM así como guías de vacunación específicas de pacientes inmunosuprimidos y en tratamiento biológico con otras patologías. Para la formulación de las recomendaciones se empleó la metodología de Modified Nominal Group Technique. Desarrollo: La vacunación en pacientes candidatos a tratamiento inmunosupresor se debe plantear antes de iniciar un tratamiento inmunosupresor siempre que la situación clínica del paciente lo permita. Se recomendarán tanto aquellas indicadas en el calendario vacunal del adulto, como algunas específicas, en función de la inmunidad previa. Si ya está instaurado el tratamiento inmunosupresor las vacunas vivas atenuadas estarán contraindicadas. Para aquéllas vacunas que dispongan de un correlato de protección se recomienda monitorizar la respuesta serológica transcurridos 1–2 meses de la última dosis.

Similar to oil, biological origin feedstock can be converted into a number of products allowing to recover the maximum value from the raw biological material, within what is nowadays called a biorefinery. Among other biological materials, microalgae are a very interesting biomass due to the high economic value of certain cellular components, such as carotenoids and polyunsaturated fatty acids. In this project, a genetically modified cyanobacteria, that produces ethanol as an extracellular product, was used as the basis of this study. In order to assess the optimal configuration of the biorefinery, different scenarios were designed, each one with different sequences of unit operations, equipment and products. With the design stage completed, an economic analysis was performed to choose the 2 scenarios with the best economic performance. Keywords: LCA, Microalgae biorefinery, Process optimization, Sustainability evaluation

Objective: The main aim of the study was to evaluate the efficacy and safety profile of Nivolumab, an immune-checkpoint-inhibitor antibody, in advanced, previously treated, Non-Small Cell Lung Cancer (NSCLC) patients, in a real world setting. Methods: We performed a retrospective, multicentre data analysis of patients who were included in the Portuguese Nivolumab Expanded Access Program (EAP). Eligibility criteria included histologically or citologically confirmed NSCLC, stage IIIB and IV, evaluable disease, sufficient organ function and at least one prior line of chemotherapy. The endpoints included Overall Response Rate (ORR), Disease Control Rate (DCR), Progression Free Survival (PFS) and Overall Survival (OS). Safety analysis was performed with the National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE), version 4.0, and immune-related Adverse Events (irAEs) were treated according to protocol treatment guidelines. Tumour response was assessed using the Response Evaluation Criteria in Solid Tumours (RECIST) version 1.1. Data was analysed using SPSS, version 21.0 (IBM Statistics). Results: From June 2015 to December 2016, a total of 229 patients with advanced NSCLC were enrolled at 30 Portuguese centres. Clinical data were collected up to the end of July 2018. The baseline median age was 64 years (range 37-83) and the majority of patients were males (70.3%) and former/current smokers (69.4%). Patients with non-squamous histology predominated (88.1%), and 67.6% of the patients had received 2 or more prior lines of chemotherapy. Out of 229 patients, data was available for 219 patients (3 patients did not start treatment, while data was unavailable in 7 patients); of the 219 patients, 15.5% were not evaluated for radiological tumour assessment, 1.4% had complete response (CR), 21% partial response (PR), 31% stable disease (SD) and 31.1% progressive disease (PD). Thus, the ORR was 22.4% and DCR was 53.4% in this population. At the time of survival analysis the median PFS was 4.91 months (95% CI, 3.89–6.11) and median OS was 13.21 months (95% CI, 9.89–16.53). The safety profile was in line with clinical trial data. Conclusions: Efficacy and safety results observed in this retrospective analysis were consistent with observations reported in clinical trials and from other centres. Resumo: Objectivo: Avaliar a eficácia e o perfil de segurança do Nivolumab, um anticorpo inibidor dos checkpoints imunológicos, em doentes com cancro do pulmão de células não pequenas (CPCNP) metastizado, previamente tratado, na prática clínica diária. Métodos: Estudo retrospectivo multicêntrico, de doentes com CPCNP incluídos no Programa de Acesso Precoce (PAP) do Nivolumab. Os critérios de inclusão eram CPCNP histologicamente ou citologicamente confirmados, estadio IIIB e IV, doença avaliável, boa função hepática e renal, e pelo menos um tratamento prévio de quimioterapia. Os objectivos principais eram a Taxa de Resposta Global (ORR), Taxa de Controlo da Doença (DCR), Sobrevivência livre de progressão (PFS) e Sobrevivência Global (OS). O perfil de segurança do fármaco foi avaliado de acordo com o National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE), versão 4.0, e os efeitos adversos imuno-relacionados (irAEs) foram tratados de acordo com as normas de orientação clínica do protocolo. A avaliação da resposta foi efectuada usando a Response Evaluation Criteria in Solid Tumours (RECIST) versão 1.1. Os dados foram analisados com recurso ao SPSS, versão 21.0 (IBM Statistics). Resultados: De Junho 2015 a Dezembro 2016, um total de 229 doentes com CPCNP avançado foram incluídos no PAP em 30 Centros portugueses. Os dados clínicos foram recolhidos até ao final de Julho de 2018. A mediana de idade basal foi de 64 anos (intervalo 37-83) e a maioria dos pacientes era do sexo masculino (70,3%) e ex-fumadores ou fumadores (69,4%). Os doentes com histologia não-escamosa predominaram (88,1%) e 67,6% dos pacientes receberam 2 ou mais linhas de quimioterapia prévias. Foi possível recolher dados de 219 doentes (dos restantes 10, 3 não iniciaram o tratamento, e os dados de 7 doentes não estavam disponíveis). Destes 219 doentes, em 15,5% não foi possível fazer avaliação radiológica do tumor, 1,4% apresentaram resposta completa (RC), 21% resposta parcial (RP), 31% doença estável (SD) e 31,1% progressão da doença (DP). Assim, nesta população, a ORR foi de 22,4% e a DCR 53,4%. À data da análise de sobrevivência, a PFS mediana foi de 4,91 meses (IC 95%, 3,89–6,11) e a OS mediana 13,21 meses (IC 95%, 9,89–16,53). O perfil de segurança foi sobreponível aos dados dos ensaios clínicos. Conclusões: Os dados de eficácia e segurança observados nesta análise retrospectiva foram concordantes com os dados dos ensaios clínicos e observados em outros estudos de vida real. Keywords: Expanded access program, Real life, Nivolumab, Non-small cell lung cancer, Safety, Efficacy, Palavras cave: Programa de acesso precoce, Vida real, Nivolumab, Cancro do Pulmão de células não pequenas, Segurança, Eficácia

Objective: To evaluate if the cancer registry database can be used to monitor treatment effectiveness using nivolumab treatment of non-small cell lung cancer (NSCLC) as an example. Method: An observational inception cohort was used, where all registered cases of NSCLC with authorisation to initiate treatment with nivolumab were monitored retrospectively to evaluate disease characteristics and response to prior treatments. Current exposure to nivolumab was prospectively characterised and treatment outcomes classified based on the clinical information registered in the patient medical record. The main outcome measure used to assess treatment effectiveness was overall survival (OS). Secondary outcomes considered were progression free survival (PFS) as a measure of effectiveness and occurrence of Adverse Drug Reaction (ADRs) as a measure of safety. Data were analysed using SPSS, version 24. Results: A total of 115 patients received treatment with nivolumab for NSCLC, between November 1st 2015 and July 31st 2016, and were registered in the database. The majority were non-squamous type (n = 107). The median OS was 11.4 months {CI95%: 11.1–11.7}, with a 1-year survival of 44%, in line with clinical trial data. Median PFS was 5.4 months {CI95%: 2.8–7.9}. Treatment was discontinued in 82 cases, most frequently due to disease progression. There were 38 cases of ADRs documented in the patient medical chart, 21 of which led to treatment discontinuation. Conclusion: The analysed data suggest that the cancer registry is a powerful tool to monitor treatment effectiveness, although considerable investment is needed to improve the medical culture of recording treatment exposure, particularly documentation of ADRs. Keywords: Immunotherapy, Registries, Lung neoplasms, Treatment effectiveness, Survival analysis, Drug-related side effects and adverse reactions

YB-1 (Y-box binding protein 1) is a multifunctional cold-shock protein that has been implicated in all hallmarks of cancer. Elevated YB-1 protein level was associated with poor prognosis in several types of cancers, including breast cancer (BC), where it is a marker of decreased overall survival (OS) and distant metastasis-free survival across all subtypes. YB-1 is also secreted by different cell types and may act as an extracellular mitogen; however the pathological implications of the secreted form of YB-1 (sYB-1) are unknown. Our purpose was to retrospectively evaluate the association between YB-1 measured by ELISA in serum and disease characteristics and outcomes in patients with BC and bone metastases (BM). In our cohort, sYB-1 was detected in the serum of 22 (50%) patients, and was associated with the presence of extra-bone metastases (p=0.044). Positive sYB-1 was also associated with faster bone disease progression (HR 3.1, 95% CI 1.09–8.95, P=0.033), but no significant differences were observed concerning OS, and time to development of skeletal-related events. Moreover, patients with positive sYB-1 also had higher levels of IL-6, a known osteoclastogenic inducer. Therefore, detection of sYB-1 in patients with BC and BM may indicate a higher tumor burden, in bone and extra-bone locations, and is a biomarker of faster bone disease progression.

This study reports new findings of Chimaera opalescens Luchetti, Iglésias et Sellos, 2011, which represent new records of this fish from Madeira and Morocco. The specimens were caught at the depths between 800 and 1221 m. Additional specimens deposited in the Natural History Museum of Funchal (MMF) were also studied as a comparative material and the results are reported herein. The new records of C. opalescens extend the previously known area of distribution of this fish further south.

Psoriatic arthritis (PsA) is a chronic inflammatory disease involving skin, peripheral joints, entheses, and axial skeleton. The disease is frequently associated with extrarticular manifestations (EAMs) and comorbidities. In order to create a protocol for PsA diagnosis and global assessment of patients with an algorithm based on anamnestic, clinical, laboratory and imaging procedures, we established a DElphi study on a national scale, named Italian DElphi in psoriatic Arthritis (IDEA). After a literature search, a Delphi poll, involving 52 rheumatologists, was performed. On the basis of the literature search, 202 potential items were identified. The steering committee planned at least two Delphi rounds. In the first Delphi round, the experts judged each of the 202 items using a score ranging from 1 to 9 based on its increasing clinical relevance. The questions posed to experts were How relevant is this procedure/observation/sign/symptom for assessment of a psoriatic arthritis patient? Proposals of additional items, not included in the questionnaire, were also encouraged. The results of the poll were discussed by the Steering Committee, which evaluated the necessity for removing selected procedures or adding additional ones, according to criteria of clinical appropriateness and sustainability. A total of 43 recommended diagnosis and assessment procedures, recognized as items, were derived by combination of the Delphi survey and two National Expert Meetings, and grouped in different areas. Favourable opinion was reached in 100% of cases for several aspects covering the following areas: medical (familial and personal) history, physical evaluation, imaging tool, second level laboratory tests, disease activity measurement and extrarticular manifestations. After performing PsA diagnosis, identification of specific disease activity scores and clinimetric approaches were suggested for assessing the different clinical subsets. Further, results showed the need for investigation on the presence of several EAMs and risk factors. In the context of any area, a rank was assigned for each item by Expert Committee members, in order to create the logical sequence of the algorithm. The final list of recommended diagnosis and assessment procedures, by the Delphi survey and the two National Expert Meetings, was also reported as an algorithm. This study shows results obtained by the combination of a DElphi survey of a group of Italian rheumatologists and two National Expert Meetings, created with the aim of establishing a clinical procedure and algorithm for the diagnosis and the assessment of PsA patients. In order to find accurate and practical diagnostic and assessment items in clinical practice, we have focused our attention on evaluating the different PsA domains. Hence, we conceived the IDEA algorithm in order to address PsA diagnosis and assessment in the context of daily clinical practice. The IDEA algorithm might eventually lead to a multidimensional approach and could represent a useful and practical tool for addressing diagnosis and for assessing the disease appropriately. However, the elaborated algorithm needs to be further investigated in daily practice, for evidencing and proving its eventual efficacy in detecting and staging PsA and its heterogeneous spectrum appropriately.

Acute diarrhea is the most common cause of morbidity and mortality in infants, where rotavirus is one of the main agents involved in severe diarrhea for children under five years. The present study aims to determine the presence of rotavirus in a vaccinated and unvaccinated pediatric population with acute diarrhea that came to the Children’s Hospital and the University Hospital of Maracaibo, State of Zulia, for observation from April 2011 to April 2012. One-hundred stool samples were collected and direct agglutination of latex particles was used for diagnosis. 43.6% of the unvaccinated children were positive (24/55) as were 33.3% (10/30) of the vaccinated children. Principally, children under 1 year were affected, predominantly males with 65.9% and females with 40%. Diarrhea due to the viral agent under study accounted for nearly half the hospitalizations for gastroenteritis. A statistically significant difference of p = 0.027 was found between the number of evacuations on the fourth day in unvaccinated (5) and vaccinated (3) children. Results of this research show rotavirus circulating in vaccinated and unvaccinated children. Therefore, the purpose of this report is to alert the medical community to consider that every child with gastroenteritis could possibly have RV.

Objective: To establish clinical guidelines for the clinical use and interpretation of motor evoked potentials (MEP) in diagnosing and monitoring patients with multiple sclerosis (MS). Recommendations for MEP use and interpretation will help us rationalise and optimise resources used in MS patient diagnosis and follow up. Method: We completed an extensive literature review and pooled our own data to produce a consensus statement with recommendations for the clinical use of MEPs in the study of MS. Results: MEPs, in addition to spinal and cranial magnetic resonance imaging (MRI), help us diagnose and assess MS patients whose disease initially presents as spinal cord syndrome and those with non-specific brain MRI findings, or a normal brain MRI and clinical signs of MS. Conclusions: Whenever possible, a multimodal evoked potential study should be performed on patients with suspected MS in order to demonstrate involvement of the motor pathway which supports a diagnosis of dissemination in space. Resumen: Objetivo: Establecer una guía clínica para la utilización clínica del estudio de potenciales evocados motores (PEM) en el diagnóstico y el seguimiento de la esclerosis múltiple (EM). Disponer de unas recomendaciones para la utilización clínica de los PEM contribuye a racionalizar y optimizar los recursos en el proceso diagnóstico y de seguimiento en los pacientes con EM. Método: Hemos llevado a cabo una extensa revisión de la literatura médica y puesto en común nuestros propios datos para consensuar recomendaciones para el uso clínico de los PEM en el estudio de la EM. Resultados: Los PEM contribuyen, junto con la resonancia magnética medular o cerebral, al diagnóstico y evaluación de los pacientes cuyo inicio clínico es un síndrome medular, que presentan hallazgos de neuroimagen poco específicos o que presentan criterios clínicos de EM con neuroimagen cerebral normal. Conclusiones: Es aconsejable realizar un estudio de potenciales evocados multimodales en pacientes con sospecha de EM para documentar la afectación de la vía motora como apoyo al diagnóstico de diseminación en espacio. Keywords: Multiple sclerosis, Motor evoked potentials, Clinical guidelines, Palabras clave: Esclerosis múltiple, Potenciales evocados motores, Guía clínica

Resumen: Objetivo: Establecer una guía clínica para la utilización clínica del estudio de potenciales evocados motores (PEM) en el diagnóstico y el seguimiento de la esclerosis múltiple (EM). Disponer de unas recomendaciones para la utilización clínica de los PEM contribuye a racionalizar y optimizar los recursos en el proceso diagnóstico y de seguimiento en los pacientes con EM. Método: Hemos llevado a cabo una extensa revisión de la literatura médica y puesto en común nuestros propios datos para consensuar recomendaciones para el uso clínico de los PEM en el estudio de la EM. Resultados: Los PEM contribuyen, junto con la resonancia magnética medular o cerebral, al diagnóstico y evaluación de los pacientes cuyo inicio clínico es un síndrome medular, que presentan hallazgos de neuroimagen poco específicos o que presentan criterios clínicos de EM con neuroimagen cerebral normal. Conclusiones: Es aconsejable realizar un estudio de potenciales evocados multimodales en pacientes con sospecha de EM para documentar la afectación de la vía motora como apoyo al diagnóstico de diseminación en espacio. Abstract: Objective: To establish clinical guidelines for the clinical use and interpretation of motor evoked potentials (MEP) in diagnosing and monitoring patients with multiple sclerosis (MS). Recommendations for MEP use and interpretation will help us rationalise and optimise resources used in MS patient diagnosis and follow up. Method: We completed an extensive literature review and pooled our own data to produce a consensus statement with recommendations for the clinical use of MEPs in the study of MS. Results: MEPs, in addition to spinal and cranial magnetic resonance imaging (MRI), help us diagnose and assess MS patients whose disease initially presents as spinal cord syndrome and those with non-specific brain MRI findings, or a normal brain MRI and clinical signs of MS. Conclusions: Whenever possible, a multimodal evoked potential study should be performed on patients with suspected MS in order to demonstrate involvement of the motor pathway which supports a diagnosis of dissemination in space. Palabras clave: Esclerosis múltiple, Potenciales evocados motores, Guía clínica, Keywords: Multiple sclerosis, Motor evoked potentials, Clinical guidelines

The aim of the present paper is a preliminary assessment and critical discussion of full-scale experimental test results recently obtained for hybrid steel-glass beams composed of a laminated glass web and steel flanges, based on the analytical Möhler method. As known, the structural response of this typology of hybrid solutions markedly depends on the stiffness and resistance of all its components, and specifically the connection, which act as a flexible shear bonding layer between the glass web and the steel flanges. Therefore, the appropriate mechanical calibration of the component materials is mandatory for accurate calculations. In order to fully characterize the used adhesive, push-out shear tests and simple shear tests were performed on small specimens. The results obtained from these small specimens are then implemented as main input mechanical parameters for the analytical model, so that this latter could be applied to the full-scale tests in view of comparative analyses. As shown, due to accurate estimation of the main mechanical properties of the adhesive layers, the presented analytical method provides rather accurate results for the examined full-scale hybrid beams, hence suggesting its application for practical calculations and pre-design considerations.

A artrodese interfalângica (IF) é um procedimento osteoarticular frequente e os fios de Kirschner são os mais usados. Outras técnicas descritas são parafusos compressivos ou, recentemente, parafuso sem cabeça, completamente roscado, Acutrak® (Acumed LLC, Hillsboro, OR). Os autores propuseram comparar duas técnicas de artrodese IF: com fios Kirschner e parafusos Acutrak®. Trata-se de um estudo retrospectivo de 2009 a 2012 englobando 67 artrodeses. Destes foram excluídos doentes com infecção, osteopenia ou perda óssea como artrite reumatóide. Obteve-se um total de 53 artrodeses: 22 com fios Kirschner (grupo I) e 31 com parafusos Acutrak® (grupo II). Foi determinada a taxa e tempo de fusão, complicações e tempo de retorno laboral. Os resultados foram analisados pelo SPSS® 20 Statistics (p

Objective: To evaluate efficacy of methotrexate treatment in peripheral arthritis of ulcerative colitis. Methods: We studied 18 patients (10/8 M/F; mean age: 38.90 yrs; range: 21-65 yrs), with peripheral arthritis (14 with polyarticular, 4 with oligoarticular subset) associate ulcerative colitis. Methotrexate 20 mg/week was administered in our patients, who were already receiving mesalazina for inflammatory bowel disease. At baseline, after 3 (T1), 6 (T2) and 12 months (T3) serological parameters (ESR and CRP), functional status (HAQ) and disease activity (VAS, GH, Ritchie articular index) were evaluated. Results: During the therapy a significant improvement was observed in disease activity, functional status and serological parameters since T1. ESR and CRP did not change at T2 and T3. Instead VAS, GH, Ritchie articular index and HAQ had a significant and gradual improvement from T1 to T3. Conclusion: Methotrexate treatment was efficacious in the treatment of peripheral arthritis associate ulcerative colitis. This drug induced improvement in disease activity, functional status and serological parameters after 3 months of therapy.

Objetivo: conocer la prevalencia del virus de hepatitis C en diferentes poblaciones de riesgo a adquirir la infección de la ciudad de Maracaibo, Venezuela. Método: la presente investigación comprendió un estudio de tipo descriptivo y transversal, cuyas variables fueron evaluadas por el análisis de correlación de Pearson. Se seleccionaron 100 drogadictos, 47 trabajadoras sexuales y 50 hemodializados, para un total de 197 individuos. Como único criterio de inclusión se tomó el hecho de presentar riesgo de contraer la infección por el virus de hepatitis C. Para la detección de anticuerpos contra el virus se utilizó la técnica de inmunoensayo enzimático de cuarta generación (Innotest HCV Ab IV). Toda muestra reactiva se confirmó por el método de inmunoblot recombinante de tercera generación (INNO-LIA HCV Ab III ), ambos de Innogenetics Lab (Bélgica). La detección del genoma viral (ARN) se realizó en aquellas muestras reactivas por ELISA e INNO-LIA por la técnica de reacción en cadena de la polimerasa, HCV-fast de Pharma Gen. Resultados: se encontró uno por ciento de prevalencia de hepatitis C en la población de drogadictos y ausencia de infección o contacto previo con el virus en trabajadoras sexuales y pacientes en hemodiálisis. Conclusiones: en el presente estudio se señala la baja prevalencia de la infección por el virus de hepatitis C en poblaciones de riesgo a adquirir la infección, por lo que se considera que esta infección no representa un problema de salud en estas poblaciones de la ciudad de Maracaibo, Venezuela.Objective: the aim of this study was to establish the prevalence of hepatitis C virus infection in different populations at risk for infection. Method: this was a descriptive, transversal study whose variables were evaluated by Pearson...s correlation analysis. Different populations were selected: 100 drug users, 47 sex workers, and 50 hemodialysis patients for a total of 197 individuals. The only inclusion criterion was the apparent risk of acquiring this viral infection. The presence of antibodies against virus was examined by ELISA IV (Innotest HCV Ab IV). Reactive samples were then tested using a recombinant assay (INNO-LIA HCV Ab III), both from Innogenetics N. V. (Belgium). The presence of viral RNA was determined in all ELISA and immunoblot-reactive samples by a nested polymerase chain reaction method (HCV-fast of Pharma Gen). Results: a prevalence of 1% was found in drug users, and absence of infection or previous contact with the virus in sex workers and hemodialysis patients. Conclusions: this study shows a very low prevalence of infection with hepatitis C virus in populations at risk for acquiring the infection, and considered that this infection is not a public health problem in these populations in Maracaibo, Venezuela.