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Idiopathic inflammatory myopathies (IIMs) are a group of rare, acquired autoimmune diseases characterized by profound muscle weakness and immune cell invasion into non-necrotic muscle. They are related to the presence of antibodies known as myositis-specific antibodies and myositis-associated antibodies, which are associated with various IIM phenotypes and the clinical prognosis. The possibility of the participation of other pathological mechanisms involved in the inflammatory response in IIM has been proposed. Such mechanisms include the overexpression of major histocompatibility complex class I in myofibers, which correlates with the activation of stress responses of the endoplasmic reticulum (ER). Taking into account the importance of the ER for the maintenance of homeostasis of the musculoskeletal system in the regulation of proteins, there is probably a relationship between immunological and non-immunological processes and autoimmunity, and an example of this might be IIM. We propose that ER stress and its relief mechanisms could be related to inflammatory mechanisms triggering a humoral response in IIM, suggesting that ER stress might be related to the triggering of IIMs and their auto-antibodies' production.

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INTRODUCTION: Refusal of physicians to prescribe insulin to their patients has been scarcely evaluated; the delay in treatment intensification hinders adequate and quality care. OBJECTIVE: To identify the perception of primary care physicians about barriers to initiate insulin treatment in patients with diabetes. METHOD: Using the Smith Index and multivariate analysis, the relevance and grouping of concepts related to barriers to insulin prescription were assessed in 81 family doctors. RESULTS: Only 35.8% of physicians showed confidence for prescribing insulin; almost half of them rated treatment intensification between moderately and little important (39.5% and 6.2%). Barriers were related to the physician (39.5%), the patient (37%), insulin treatment (11.1%) and the institution (6.2%); 6.2 % of physicians did not perceive any barrier. The barriers were grouped in 5 factors that explained 62.48% of the variance: patient cultural level, lack of medical skills, fear of adverse events, insecurity and lack of training. CONCLUSION: Clinical inertia was not the result of a complex medical condition or patient comorbidities, but of doctor's perception and confidence in his/her clinical and communication skills.

INTRODUCCIÓN: Poco se ha evaluado el rechazo de los médicos a prescribir insulina a sus pacientes; el retraso en intensificar el tratamiento impide una atención adecuada y de calidad. OBJETIVO: Identificar la percepción de los médicos acerca de las barreras para iniciar la insulina en los pacientes con diabetes. MÉTODO: Por Índice Smith y análisis multivariado, en 81 médicos familiares se evaluó la relevancia y agrupación de los conceptos relacionados con las barreras para la prescripción de insulina. RESULTADOS: 35.8 % de los médicos mostró confianza en prescribir insulina; casi la mitad calificó la intensificación del tratamiento entre moderadamente y poco importante (39.5 y 6.2 %). Las barreras se relacionaron con el médico (39.5 %), el paciente (37 %), el tratamiento con insulina (11.1 %) y la institución (6.2 %); 6.2 % de los médicos no percibió ninguna barrera. Las barreras se agruparon en cinco factores, que explicaron 62.48 % de la varianza: cultura de los pacientes, falta de habilidades, miedo a los eventos adversos, inseguridad y falta de capacitación. CONCLUSIÓN: La inercia clínica no resultó de una condición clínica compleja o comorbilidades del paciente, sino de la percepción del médico y de su confianza en sus habilidades clínicas y comunicativas.

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Resumen Introducción: Poco se ha evaluado el rechazo de los médicos a prescribir insulina a sus pacientes; el retraso en intensificar el tratamiento impide una atención adecuada y de calidad. Objetivo: Identificar la percepción de los médicos acerca de las barreras para iniciar la insulina en los pacientes con diabetes. Método: Por Índice Smith y análisis multivariado, en 81 médicos familiares se evaluó la relevancia y agrupación de los conceptos relacionados con las barreras para la prescripción de insulina. Resultados: 35.8 % de los médicos mostró confianza en prescribir insulina; casi la mitad calificó la intensificación del tratamiento entre moderadamente y poco importante (39.5 y 6.2 %). Las barreras se relacionaron con el médico (39.5 %), el paciente (37 %), el tratamiento con insulina (11.1 %) y la institución (6.2 %); 6.2 % de los médicos no percibió ninguna barrera. Las barreras se agruparon en cinco factores, que explicaron 62.48 % de la varianza: cultura de los pacientes, falta de habilidades, miedo a los eventos adversos, inseguridad y falta de capacitación. Conclusión: La inercia clínica no resultó de una condición clínica compleja o comorbilidades del paciente, sino de la percepción del médico y de su confianza en sus habilidades clínicas y comunicativas.

Abstract Introduction: Refusal of physicians to prescribe insulin to their patients has been scarcely evaluated; the delay in treatment intensification hinders adequate and quality care. Objective: To identify the perception of primary care physicians about barriers to initiate insulin treatment in patients with diabetes. Method: Using the Smith Index and multivariate analysis, the relevance and grouping of concepts related to barriers to insulin prescription were assessed in 81 family doctors. Results: Only 35.8% of physicians showed confidence for prescribing insulin; almost half of them rated treatment intensification between moderately and little important (39.5% and 6.2%). Barriers were related to the physician (39.5%), the patient (37%), insulin treatment (11.1%) and the institution (6.2%); 6.2 % of physicians did not perceive any barrier. The barriers were grouped in 5 factors that explained 62.48% of the variance: patient cultural level, lack of medical skills, fear of adverse events, insecurity and lack of training. Conclusion: Clinical inertia was not the result of a complex medical condition or patient comorbidities, but of doctor’s perception and confidence in his/her clinical and communication skills.

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Introduction: Cardiovascular parameters disruption can be found in patients at early stages of rheumatoid arthritis (RA). The primary endpoint of this study was the reduction of arterial stiffness in RA patients without traditional cardiovascular risk factors or previous comorbidities, measured by cardio-ankle vascular index (CAVI) through the enalapril intervention. The secondary endpoints were the enalapril influence on carotid femoral pulse wave velocity (cfPWV), carotid intima media thickness (cIMT), carotid artery distensibility (cDistensibility), Young's incremental elastic modulus (Einc)]. Materials and Methods: Fifty-three patients were enrolled in a clinical, randomized, closed-label trial. The subjects were randomly assigned into two groups: One receiving 5 mg of enalapril (27) or placebo (26), both twice a day. The drug was acquired at Victory Enterprises®. The placebo was kindly provided by the Universidad de Guadalajara (UdeG), as well as the blinding into two groups: A and B. Enalapril and placebo were packed into bottles without labeling. Clinical assessment included a structured questionnaire to gather demographic and clinical variables as well as determination of CAVI, cfPWV, cIMT, carotid artery distensibility and Einc. The whole set of evaluations were analyzed at the baseline and at the end of 12 weeks of intervention. Results: The CAVI measurement at baseline was 7.1 ± 1.4 and increased up to 7.5 ± 1.2 at the end of 12 weeks. Meanwhile, the enalapril group was as follows: 7.4 ± 1.2 and at the of intervention, reduced to 7.1 ± 0.9. A reduction in delta CAVI of 0.21 in the enalapril intervention group was found. In contrast, an increase of 0.39 was observed in the placebo group. The delta CAVI reduction was not influenced by age or peripheral systolic blood pressure (pSBP). Discussion: Enalapril seems to be effective in CAVI reduction in RA patients. The effect of enalapril intervention on arterial stiffness translated to the clinical context might be interpreted as a reduction of 6.4 years of arterial aging. Trial Registration: The protocol was approved by the Institutional Review Board with the register CI-0117 from UdeG, and 0211/18 from Hospital Civil "Dr. Juan I. Menchaca", Secretaría de Salud Jalisco: DGSP/DDI/D.INV.28/18 and retrospectively registered at ClinicalTrials.gov Protocol Registration and Results System: NCT03667131.

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Endovascular treatment and prognosis of intracranial aneurysms are based on size and volume, which demand more accurate neuroimaging techniques. Aneurysm volume calculation is important to choose endovascular treatment modalities and packing density calculation. Of all these methods, it remains unknown which one is the most accurate to calculate aneurysm volume. The objective of this study is to compare the accuracy of three angiography-based versus three tomographic-based methods which calculate aneurysm volume. A retrospective study which included patients with ruptured and unruptured cerebral aneurysms diagnosed by angiogram and computed tomography angiography (CTA) was done. The accuracy of each method was assessed with an ellipsoid glass model of known volume, which helped us to adjust variation in volumetric measurements done with AngioSuite© and AngioCalc© softwares (based on angiographic and tomographic images), 3D-rotational angiography and 3D-CTA (tridimensional computed tomography angiography), based on measurements of diameters such as maximal width and maximal height. Descriptive statistics, ANOVA for repetitive samples and t test were used. We included 89 patients (126 saccular intracraneal aneurysms). AngioSuite© software (angiography-based) showed more accuracy compared to other methods in our control model. The geometric system (AngioCalc) based on CTA images was statistically different from all other methods studied. AngioCalc (CTA-based) demonstrated a significant difference compared with other methods hence, it may overestimate volume measurements. AngioSuite

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OBJECTIVES: To conduct an economic evaluation of intracranial pressure (ICP) monitoring on the basis of current evidence from pediatric patients with severe traumatic brain injury, through a statistical model. METHODS: The statistical model is a decision tree, whose branches take into account the severity of the lesion, the hospitalization costs, and the quality-adjusted life-year for the first 6 months post-trauma. The inputs consist of probability distributions calculated from a sample of 33 surviving children with severe traumatic brain injury, divided into two groups: with ICP monitoring (monitoring group) and without ICP monitoring (control group). The uncertainty of the parameters from the sample was quantified through a probabilistic sensitivity analysis using the Monte-Carlo simulation method. The model overcomes the drawbacks of small sample sizes, unequal groups, and the ethical difficulty in randomly assigning patients to a control group (without monitoring). RESULTS: The incremental cost in the monitoring group was Mex$3,934 (Mexican pesos), with an increase in quality-adjusted life-year of 0.05. The incremental cost-effectiveness ratio was Mex$81,062. The cost-effectiveness acceptability curve had a maximum at 54% of the cost effective iterations. The incremental net health benefit for a willingness to pay equal to 1 time the per capita gross domestic product for Mexico was 0.03, and the incremental net monetary benefit was Mex$5,358. CONCLUSIONS: The results of the model suggest that ICP monitoring is cost effective because there was a monetary gain in terms of the incremental net monetary benefit.

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BACKGROUND: Meningeal melanomatosis is an extra-axial well-encapsulated malignant tumour with diffuse meningeal growth and dark coloration (due to high melanin contents), while meningeal melanocytoma is the focalized benign variant. Melanocytic lesions may be secondary to melanoma or be histologically benign, however, their diffuse nature makes them impossible to cure. Melanocytosis is a diffuse tumour that can form solitary extra-axial tumours, which invades the parenchyma and presents signs of malignancy with increased mitosis and Ki67, observed in 1 to 6% of immunopathological exams. Melanoma of the leptomeninges, presents signs of malignancy with anaplastic cells, which cluster in fascicles of melanin in the cytoplasm, with more than 3 atypical mitoses per field and Ki67 presenting in more than 6% of the immunopathological fields analysed. CLINICAL CASE: We present the case of a patient with long-term meningeal melanomatosis, with progressive neurologic deficit and characteristic radiologic features, and another case of meningeal melanocytoma. CONCLUSIONS: Benign melanocytic neoplasms of the central nervous system must be treated aggressively in the early phases with strict follow-up to avoid progression to advanced phases that do not respond to any treatment method. Unfortunately, the prognosis for malignant melanocytic lesions is very poor irrespective of the method of treatment given.

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BACKGROUND: Whether cerebral arteriovenous malformations (AVMs) should be treated remains an ongoing debate. Nevertheless, there is a need for predictive factors that assist in labelling lesions as low or high risk for future rupture. Our aim was to design a new classification that would consider hemodynamic and anatomic factors in the rapid assessment of rupture risk in patients with AVMs. METHODS: This was a retrospective study that included 639 patients with ruptured and unruptured AVMs. We proposed a new classification score (1-4 points) for AVM rupture risk using three factors: feeding artery mean velocity (Vm), nidus size, and type of venous drainage. We employed descriptive statistics and logistic regression analysis. RESULTS: A total of 639 patients with cerebral AVMs, 388 (60%) had unruptured AVMs and 251 (40%) had ruptured AVMs. Logistic regression analysis revealed a significant effect of Vm, nidus size, and venous drainage type in accounting for the variability of rupture odds (P = 0.0001, R2 = 0.437) for patients with AVMs. Based in the odds ratios, grades 1 and 2 of the proposed classification were corresponded to low risk of hemorrhage, while grades 3 and 4 were associated with hemorrhage: 1 point OR = (0.107 95% CI; 0.061-0.188), 2 point OR = (0.227 95% CI; 0.153-0.338), 3 point OR = (3.292 95% CI; 2.325-4.661), and 4 point OR = (23.304 95% CI; 11.077-49.027). CONCLUSION: This classification is useful and easy to use, and it may allow for the individualisation of each cerebral AVM and the assessment of rupture risk based on a model of categorisation.

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Introducción: El traumatismo craneoencefálico severo (TCES) es una entidad grave. La monitorización de la presión intracraneal (PIC) permite dirigir el tratamiento, el cual es de limitado acceso en países en vías de desarrollo. Objetivo: Describir la experiencia clínica de pacientes pediátricos con TCES. Pacientes y método: Se incluyeron pacientes con TCES, edad entre 1 y 17 años, previo consentimiento informado de los padres y/o tutores. Se excluyeron pacientes con enfermedades crónicas o retraso psicomotor. Los pacientes ingresaron desde el Servicio de Urgencia, donde se les realizó scanner cerebral (TAC), clasificándose las lesiones por Escala de Marshall. Los pacientes fueron divididos en 2 grupos según criterio neuroquirúrgico: con monitorización (CM) y sin monitorización (SM) de presión intracraneana. La monitorización de la PIC se realizó a través de un catéter intraparenquimatoso 3PN Spiegelberg conectado a un monitor Spiegelberg HDM 26. Los pacientes fueron tratados de acuerdo a las guías pediátricas para TCES. Se consideró la supervivencia como los días transcurridos entre el ingreso hospitalario y el fallecimiento, o su evaluación por Escala de Glasgow para un seguimiento de 6 meses. Resultados: Cuarenta y dos pacientes (CM = 14 y SM= 28). Aquellos con monitorización tenían menor puntuación de la escala de coma de Glasgow y clasificación de Marshall con peor pronóstico. En ellos la supervivencia fue menor y el resultado moderado a bueno. No se registraron complicaciones con el uso del catéter de PIC. Conclusión: Pacientes con monitorización tuvieron mayor gravedad al ingreso y una mayor mortalidad; sin embargo, el resultado funcional de los sobrevivientes fue de moderado a bueno. Se requiere de la realización de ensayos clínicos aleatorizados para definir el impacto de la monitorización de la PIC en la supervivencia y calidad de vida en estos pacientes.

Introduction: Severe traumatic brain injury (TBI) is a serious condition. Intracranial pressure (ICP) monitoring can be used to direct treatment, which is of limited access in developing countries. Objective: To describe the clinical experience of pediatric patients with severe TBI. Patients and Method: A clinical experience in patients with severe TBI was conducted. Age was 1-17 years, exclusion criteria were chronic illness and psicomotor retardation. Informed consent was obtained in each case. Two groups were formed based on the criterion of neurosurgeons: with and without intracraneal pressure (ICP) monitoring. PIC monitoring was performed through a 3PN Spiegelberg catheter and a Spiegelberg HDM 26 monitor. Patients were treated according international pediatric guides. The characteristics of both groups are described at 6 months of follow-up. Results: Forty-two patients (CM=14 and SM=28). Those in the CM Group had lower Glasgow coma scale score and Marshall classification with poorer prognosis. Among them survival rate was lower, although the outcome was from moderate to good. No complications were reported with the use of the ICP catheter. Conclusion: Patients with ICP monitoring had greater severity at admission and an increased mortality; however, the outcome for the survivors was from moderate to good. It is necessary to conduct randomized clinical trials to define the impact of ICP monitoring on survival and quality of life in severe TBI patients.

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Agricultural intensification in the tropics is one way to meet rising global food demand in coming decades(1,2). Although this strategy can potentially spare land from conversion to agriculture(3), it relies on large material inputs. Here we quantify one such material cost, the phosphorus fertilizer required to intensify global crop production atop phosphorus-fixing soils and achieve yields similar to productive temperate agriculture. Phosphorus-fixing soils occur mainly in the tropics, and render added phosphorus less available to crops(4,5). We estimate that intensification of the 8-12% of global croplands overlying phosphorus-fixing soils in 2005 would require 1-4 Tg P yr(-1) to overcome phosphorus fixation, equivalent to 8-25% of global inorganic phosphorus fertilizer consumption that year. This imposed phosphorus 'tax' is in addition to phosphorus added to soils and subsequently harvested in crops, and doubles (2-7 Tg P yr(-1)) for scenarios of cropland extent in 2050(6). Our estimates are informed by local-, state- and national-scale investigations in Brazil, where, more than any other tropical country, low-yielding agriculture has been replaced by intensive production. In the 11 major Brazilian agricultural states, the surplus of added inorganic fertilizer phosphorus retained by soils post harvest is strongly correlated with the fraction of cropland overlying phosphorus-fixing soils (r(2) = 0.84, p < 0.001). Our interviews with 49 farmers in the Brazilian state of Mato Grosso, which produces 8% of the world's soybeans mostly on phosphorus-fixing soils, suggest this phosphorus surplus is required even after three decades of high phosphorus inputs. Our findings in Brazil highlight the need for better understanding of long-term soil phosphorus fixation elsewhere in the tropics. Strategies beyond liming, which is currently widespread in Brazil, are needed to reduce phosphorus retention by phosphorus-fixing soils to better manage the Earth's finite phosphate rock supplies and move towards more sustainable agricultural production.

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