Effect of flow change on brain injury during an experimental model of differential hypoxaemia in cardiogenic shock supported by extracorporeal membrane oxygenation.

Differential hypoxaemia (DH) is common in patients supported by femoral veno-arterial extracorporeal membrane oxygenation (V-A ECMO) and can cause cerebral hypoxaemia. To date, no models have studied the direct impact of flow on cerebral damage. We investigated the impact of V-A ECMO flow on brain injury in an ovine model of DH. After inducing severe cardiorespiratory failure and providing ECMO support, we randomised six sheep into two groups: low flow (LF) in which ECMO was set at 2.5 L min-1 ensuring that the brain was entirely perfused by the native heart and lungs, and high flow (HF) in which ECMO was set at 4.5 L min-1 ensuring that the brain was at least partially perfused by ECMO. We used invasive (oxygenation tension-PbTO2, and cerebral microdialysis) and non-invasive (near infrared spectroscopy-NIRS) neuromonitoring, and euthanised animals after five hours for histological analysis. Cerebral oxygenation was significantly improved in the HF group as shown by higher PbTO2 levels (+ 215% vs - 58%, p = 0.043) and NIRS (67 ± 5% vs 49 ± 4%, p = 0.003). The HF group showed significantly less severe brain injury than the LF group in terms of neuronal shrinkage, congestion and perivascular oedema (p < 0.0001). Cerebral microdialysis values in the LF group all reached the pathological thresholds, even though no statistical difference was found between the two groups. Differential hypoxaemia can lead to cerebral damage after only a few hours and mandates a thorough neuromonitoring of patients. An increase in ECMO flow was an effective strategy to reduce such damages.

An innovative ovine model of severe cardiopulmonary failure supported by veno-arterial extracorporeal membrane oxygenation.

Refractory cardiogenic shock (CS) often requires veno-arterial extracorporeal membrane oxygenation (VA-ECMO) to sustain end-organ perfusion. Current animal models result in heterogenous cardiac injury and frequent episodes of refractory ventricular fibrillation. Thus, we aimed to develop an innovative, clinically relevant, and titratable model of severe cardiopulmonary failure. Six sheep (60 ± 6 kg) were anaesthetized and mechanically ventilated. VA-ECMO was commenced and CS was induced through intramyocardial injections of ethanol. Then, hypoxemic/hypercapnic pulmonary failure was achieved, through substantial decrease in ventilatory support. Echocardiography was used to compute left ventricular fractional area change (LVFAC) and cardiac Troponin I (cTnI) was quantified. After 5 h, the animals were euthanised and the heart was retrieved for histological evaluations. Ethanol (58 ± 23 mL) successfully induced CS in all animals. cTnI levels increased near 5000-fold. CS was confirmed by a drop in systolic blood pressure to 67 ± 14 mmHg, while lactate increased to 4.7 ± 0.9 mmol/L and LVFAC decreased to 16 ± 7%. Myocardial samples corroborated extensive cellular necrosis and inflammatory infiltrates. In conclusion, we present an innovative ovine model of severe cardiopulmonary failure in animals on VA-ECMO. This model could be essential to further characterize CS and develop future treatments.

Resuscitation fluid practices in Brazilian intensive care units: a secondary analysis of Fluid-TRIPS. / Práticas de ressuscitação volêmica em unidades de terapia intensiva brasileiras: uma análise secundária do estudo Fluid-TRIPS.

OBJECTIVE: To describe fluid resuscitation practices in Brazilian intensive care units and to compare them with those of other countries participating in the Fluid-TRIPS. METHODS: This was a prospective, international, cross-sectional, observational study in a convenience sample of intensive care units in 27 countries (including Brazil) using the Fluid-TRIPS database compiled in 2014. We described the patterns of fluid resuscitation use in Brazil compared with those in other countries and identified the factors associated with fluid choice. RESULTS: On the study day, 3,214 patients in Brazil and 3,493 patients in other countries were included, of whom 16.1% and 26.8% (p < 0.001) received fluids, respectively. The main indication for fluid resuscitation was impaired perfusion and/or low cardiac output (Brazil: 71.7% versus other countries: 56.4%, p < 0.001). In Brazil, the percentage of patients receiving crystalloid solutions was higher (97.7% versus 76.8%, p < 0.001), and 0.9% sodium chloride was the most commonly used crystalloid (62.5% versus 27.1%, p < 0.001). The multivariable analysis suggested that the albumin levels were associated with the use of both crystalloids and colloids, whereas the type of fluid prescriber was associated with crystalloid use only. CONCLUSION: Our results suggest that crystalloids are more frequently used than colloids for fluid resuscitation in Brazil, and this discrepancy in frequencies is higher than that in other countries. Sodium chloride (0.9%) was the crystalloid most commonly prescribed. Serum albumin levels and the type of fluid prescriber were the factors associated with the choice of crystalloids or colloids for fluid resuscitation.

OBJETIVO: Descrever as práticas de ressuscitação volêmica em unidades de terapia intensiva brasileiras e compará-las com as de outros países participantes do estudo Fluid-TRIPS. MÉTODOS: Este foi um estudo observacional transversal, prospectivo e internacional, de uma amostra de conveniência de unidades de terapia intensiva de 27 países (inclusive o Brasil), com utilização da base de dados Fluid-TRIPS compilada em 2014. Descrevemos os padrões de ressuscitação volêmica utilizados no Brasil em comparação com os de outros países e identificamos os fatores associados com a escolha dos fluidos. RESULTADOS: No dia do estudo, foram incluídos 3.214 pacientes do Brasil e 3.493 pacientes de outros países, dos quais, respectivamente, 16,1% e 26,8% (p < 0,001) receberam fluidos. A principal indicação para ressuscitação volêmica foi comprometimento da perfusão e/ou baixo débito cardíaco (Brasil 71,7% versus outros países 56,4%; p < 0,001). No Brasil, a percentagem de pacientes que receberam soluções cristaloides foi mais elevada (97,7% versus 76,8%; p < 0,001), e solução de cloreto de sódio a 0,9% foi o cristaloide mais comumente utilizado (62,5% versus 27,1%; p < 0,001). A análise multivariada sugeriu que os níveis de albumina se associaram com o uso tanto de cristaloides quanto de coloides, enquanto o tipo de prescritor dos fluidos se associou apenas com o uso de cristaloides. CONCLUSÃO: Nossos resultados sugerem que cristaloides são usados mais frequentemente do que coloides para ressuscitação no Brasil, e essa discrepância, em termos de frequências, é mais elevada do que em outros países. A solução de cloreto de sódio 0,9% foi o cristaloide mais frequentemente prescrito. Os níveis de albumina sérica e o tipo de prescritor de fluidos foram os fatores associados com a escolha de cristaloides ou coloides para a prescrição de fluidos.

Celastrol Efficacy by Oral Administration in the Adjuvant-Induced Arthritis Model.

Background: We previously demonstrated that celastrol has significant anti-inflammatory and bone protective effects when administered via the intraperitoneal route. For further preclinical evaluation, an effective oral administration of celastrol is crucial. Here we aimed to study the therapeutic dose range for its oral administration. Methods: Celastrol (1-25 µg/g/day, N = 5/group) was administrated orally to female adjuvant-induced arthritis (AIA) rats after 8 days of disease induction for a period of 14 days. A group of healthy (N = 8) and arthritic (N = 15) gender- and age-matched Wistar rats was used as controls. During the treatment period, the inflammatory score, ankle perimeter, and body weight were measured. At the end of the treatment, the animals were sacrificed, blood was collected for clinical pathology, necropsy was performed with collection of internal organs for histopathological analysis, and paw samples were used for disease scoring. Results: Doses higher than 2.5 µg/g/day of celastrol reduced the inflammatory score and ankle swelling, preserved joint structure, halted bone destruction, and diminished the number of synovial CD68+ macrophages. Bone resorption and turnover were also reduced at 5 and 7.5 µg/g/day doses. However, the dose of 7.5 µg/g/day was associated with thymic and liver lesions, and higher doses showed severe toxicity. Conclusion: Oral administration of celastrol above 2.5 µg/g/day ameliorates arthritis. This data supports and gives relevant information for the development of a preclinical test of celastrol in the setting of a chronic model of arthritis since rheumatoid arthritis is a long-term disease.

Efficacy, Safety, and Sample Quality of Ultrasound-Guided Synovial Needle Biopsy in Clinical Practice and Research: A Prospective Observational Study.

OBJECTIVE: To study the efficacy, tolerability, safety, and sampling variation of ultrasound (US)-guided synovial biopsies performed in clinical practice and research. METHODS: We included all patients who had a US-guided synovial needle biopsy from November 2013 to January 2018. Patients were evaluated for procedure safety and tolerability. Usefulness of synovial biopsy was considered based on contribution for achieving the proposed aims. We analyzed samples for presence and quality of synovial tissue, synovitis score/grade, and pathotype. Variation across patients, samples, section levels, and sampling order was assessed. RESULTS: A total of 64 US-guided synovial biopsies were performed (n = 52 in clinical practice, n = 12 in research). Patient tolerability (70% no/mild discomfort) was remarkably high. There was no significant aggravation of symptoms or US synovitis in the biopsied joint. Procedures were overall safe, with few minor, 2 moderate, and no major adverse events. Usefulness of US-guided synovial biopsies was high, both in clinical practice (37% direct diagnostic impact, 100% positive/95% negative predictive values for infection) and in research (92% success). Synovial tissue was retrieved in 88% of biopsies, with a median of 75% gradable samples. There was significant variation in sample quality and synovitis features across patients and samples, but not between different section levels. Samples collected later in the procedure had a lower frequency of synovial tissue and were poorly concordant in pathotype with those collected earlier. CONCLUSION: US-guided synovial needle biopsy is an effective, safe, and well-tolerated means to collect good quality synovial tissue for clinical and research purposes. Samples collected for different aims should be retrieved in parallel, rather than sequentially.

Cell sources of inflammatory mediators present in bone marrow areas inside the meniscus.

PURPOSE: To demonstrate the production of inflammatory mediators by cells located in bone marrow spaces inside rodent menisci. METHODS: Mice subjected to transection of the medial collateral and anterior cruciate ligaments and meniscotomy (osteoarthritis model) or to a sham procedure, as well as non-operated (naive) mice and rats, had knee joints excised. Tissues were stained with hematoxylin-eosin and tartrate-resistant acid phosphatase (TRAP). CD68+ cells, inducible nitric oxide synthase (iNOS), interleukin (IL)-1ß, and tumor necrosis factor (TNF) expression were detected using immunohistochemistry. RESULTS: Lamellar ossified areas, bone-entrapped osteocytes and bone marrow spaces were found inside menisci of one week up to 6 months-old naïve mice, regardless of gender. Menisci from naive rats also showed the same pattern with bone marrow areas. CD68+ cells were identified in bone marrow areas inside the meniscus of mice. TRAP+ osteoclasts, and hematogenous precursors expressing IL-1ß, TNF, and iNOS were identified inside bone marrow areas in meniscal samples from both naïve and sham operated mice. Quantitative immunoexpression of IL-1 ß, TNF and iNOS was more intense, P = 0.0194, 0.0293, 0.0124, respectively, in mouse knees from mice sacrificed 49 days after being subjected to an osteoarthritis (OA) model as compared to sham operated animals. CONCLUSION: We provide novel data showing that rodent menisci display bone marrow areas with cells able to produce inflammatory mediators. Immunoexpression of inflammatory mediators in those bone marrow areas is significantly more pronounced in mice subjected to experimental OA.

Revisión de casos de schwannoma en la Unidad de Miembro Superior del Servicio de Cirugía Plástica de La Coruña, España / Case review of schwannoma at the Superior Member Unit, La Coruña Plastic Surgery Service, Spain

Introducción y Objetivo: Los tumores derivados de las células de Schwann (schwannomas, neurinomas o neurilemomas) son los más frecuentes de los dependientes de tejido nervioso en el miembro superior. Frecuentemente se confunden con tumores de otra índole, principalmente con los derivados de tejido adiposo o lipomas. Aunque pueden compartir algunas características clínicas, existen ciertos síntomas específicos de los schwannomas que sugieren su diagnóstico y permiten realizar el tratamiento adecuado. En algunos casos, son necesarias técnicas microquirúrgicas para su extirpación y posterior reparación del nervio afectado. El presente trabajo pretende realizar una evaluación epidemiológica en nuestro medio, mediante revisión retrospectiva de casos, teniendo en cuenta la presentación clínica, el diagnóstico, el tratamiento y la evolución presentada tras el tratamiento mediante la existencia o no de secuelas. Material y Método: Revisamos retrospectivamente 10 casos de schwannoma en miembro superior recogidos en el Servicio de Cirugía Plástica de La Coruña (España) a lo largo de 4 años. Evaluamos la edad, género, localización, signos clínicos, estudios electrofisiológicos, imágenes, tratamiento, seguimiento y secuelas. Realizamos el análisis mediante tablas comparativo-descriptivas. Resultados: El 60% de la muestra fueron varones, con edad media de 47.5 años. El nervio mediano fue el más frecuentemente afectado. El dolor local y las parestesias los síntomas más frecuentes, con Tinel positivo en el 90% de los casos. El 30% de los pacientes presentó bloqueo nervioso (motor/sensitivo) en la electrofisiología y 2 casos discontinuidad del nervio. La escisión microquirúrgica bajo magnificación óptica fue el tratamiento de elección en el 80% de los casos; 20% necesitaron injerto de nervio sural para la reparación del nervio afectado. Con un seguimiento medio de 12 meses, el 80% de los casos no presentó secuelas tras el tratamiento. Conclusiones: Los schwannomas suelen producir poca sintomatología y cuando lo hacen, la clínica suele ser local. Su origen más frecuente en nuestra serie fue el nervio mediano. El diagnóstico adecuado exige sospecha clínica y confirmación mediante resonancia magnética. Los tumores mal delimitados pueden incluir pequeños fascículos nerviosos que, a pesar de la magnificación óptica, resulta imposible identificar y conservar. En la medida de lo técnicamente posible se deben respetar los fascículos sanos, o en su defecto, reconstruir el fascículo nervioso para restablecer su continuidad

Background and Objective: Tumors derived from Schwann cells (schwannomas, neurinomas or neurilemomas) are the most frequently nervous tissue tumors of the upper limb. They usually get confused with other kind of tumors, mainly those derived from adipose tissue also call lipomas. Although they may share some clinical characteristics, there are certainly some specific symptoms in schwannomas that allow making a correct differential diagnosis. In some cases, microsurgical techniques are necessary for its removal and subsequent reconstruction of the affected nerve. The present study carries out a retrospective epidemiological review of a series of cases in our center, considering the clinical presentation, diagnosis, treatment and the outcomes in terms of the presence or absence of sequelae. Methods: We retrospectively reviewed 10 cases of schwannoma in the upper member collected in the Plastic Surgery Service of La Coruña (Spain) over the last 4 years. We describe age, gender, location, clinical signs, electrophysiological studies, images, treatment, follow-up and sequelae. We perform the analysis using comparative-descriptive tables. Results: Sixty percent of the sample were men, the median age was 47.5 years, and the median nerve was the most frequently affected. Local pain and paresthesias were the most frequent symptoms, with Tinel sign in 90% of the cases. Thirty percent of patients had nerve block (motor / sensitive) in electrophysiology study. Two cases presented discontinuity of the nerve. The microsurgical excision under optical magnification was the choice for treatment in 80% of the cases and 20% needed a sural nerve graft for repairing the affected nerve. With a mean follow-up of 12 months, 80% of the cases did not present sequelae after treatment. Conclusions: Schwannomas usually produce limited symptomatology and when they do, are oftenly local symptoms. The most frequent origin was the median nerve. The adequate diagnosis requires clinical suspicion and confirmation by magnetic resonance. Those ill-defined tumors may include small nerve fascicles that, despite of optical magnification, are impossible to identify and preserve. As far as it is technically possible, healthy fascicles should be respected or if not, reconstructed to restore its continuity

Early arthritis induces disturbances at bone nanostructural level reflected in decreased tissue hardness in an animal model of arthritis.

INTRODUCTION: Arthritis induces joint erosions and skeletal bone fragility. OBJECTIVES: The main goal of this work was to analyze the early arthritis induced events at bone architecture and mechanical properties at tissue level. METHODS: Eighty-eight Wistar rats were randomly housed in experimental groups, as follows: adjuvant induced arthritis (AIA) (N = 47) and a control healthy group (N = 41). Rats were monitored during 22 days for the inflammatory score, ankle perimeter and body weight and sacrificed at different time points (11 and 22 days post disease induction). Bone samples were collected for histology, micro computed tomography (micro-CT), 3-point bending and nanoindentation. Blood samples were also collected for bone turnover markers and systemic cytokine quantification. RESULTS: At bone tissue level, measured by nanoindentation, there was a reduction of hardness in the arthritic group, associated with an increase of the ratio of bone concentric to parallel lamellae and of the area of the osteocyte lacuna. In addition, increased bone turnover and changes in the microstructure and mechanical properties were observed in arthritic animals, since the early phase of arthritis, when compared with healthy controls. CONCLUSION: We have shown in an AIA rat model that arthritis induces very early changes at bone turnover, structural degradation and mechanical weakness. Bone tissue level is also affected since the early phase of arthritis, characterized by decreased tissue hardness associated with changes in bone lamella organization and osteocyte lacuna surface. These observations highlight the pertinence of immediate control of inflammation in the initial stages of arthritis.

Effects of tofacitinib in early arthritis-induced bone loss in an adjuvant-induced arthritis rat model.

Objectives: The main goal of this work was to analyse how treatment intervention with tofacitinib prevents the early disturbances of bone structure and mechanics in the rat model of adjuvant-induced arthritis. This is the first study to access the impact of tofacitinib on the skeletal bone effects of inflammation. Methods: Fifty Wistar rats with adjuvant-induced arthritis were randomly housed in experimental groups, as follows: non-arthritic healthy group (n = 20); arthritic non-treated group (n = 20); and 10 animals undergoing tofacitinib treatment. Rats were monitored during 22 days after disease induction for the inflammatory score, ankle perimeter and body weight. Healthy non-arthritic rats were used as controls for comparison. After 22 days of disease progression, rats were killed and bone samples collected for histology, micro-CT, three-point bending and nanoindentation analysis. Blood samples were also collected for quantification of bone turnover markers and systemic cytokines. Results: At the tissue level, measured by nanoindentation, tofacitinib increased bone cortical and trabecular hardness. However, micro-CT and three-point bending tests revealed that tofacitinib did not reverse the effects of arthritis on the cortical and trabecular bone structure and on mechanical properties. Conclusion: Possible reasons for these observations might be related to the mechanism of action of tofacitinib, which leads to direct interactions with bone metabolism, and/or to the kinetics of its bone effects, which might need longer exposure.

Chronic Hyperglycemia Modulates Rat Osteoporotic Cortical Bone Microarchitecture into Less Fragile Structures.

There is controversy concerning the diabetes impact on bone quality, notorious in type 2 diabetic postmenopausal women. One pointed cause might be uncontrolled glycemia. In this study, the effect of chronic hyperglycemia in bone turnover, morphology, and biomechanics was evaluated in female Wistar rats in the presence/absence of estrogens (ovariectomy). Animals (n = 28) were divided into sham, ovariectomized (OVX), hyperglycemic (streptozotocin 40 mg/kg, single-dose i.p.-STZ), and hyperglycemic-ovariectomized (STZ + OVX) animals. Blood biomarkers were estimated 60 days postovariectomy. Body weight, vertebral microarchitecture (L4-histomorphometry), femur biomechanical properties (bending tests), tibia ultrastructure (scanning electron microscopy), and femur and urinary calcium (atomic absorption) were also evaluated. The increased PINP/CTX ratio of hyperglycemic animals and the similar ratio between STZ + OVX and healthy animals contrasting with the lower ratio of OVX (in line with its histomorphometric data) suggest a tendency for improved bone formation in hyperglycemic-ovariectomized animals. The increased tibia medullar canal, which contrasts with the unaffected cortical thickness of both hyperglycemic groups while that of OVX decreased, was associated to the increased stiffness and strength of STZ + OVX bones compared to those of OVX, in line with the observed ultrastructure. Concluding, chronic hyperglycemia in ovariectomized female rats causes bone morphological changes that translate positively in the ultrastructure and mechanical properties of cortical bones.

Effect of celastrol on bone structure and mechanics in arthritic rats.

OBJECTIVE: Rheumatoid arthritis (RA) is characterised by chronic inflammation leading to articular bone and cartilage damage. Despite recent progress in RA management, adverse effects, lack of efficacy and economic barriers to treatment access still limit therapeutic success. Therefore, safer and less expensive treatments that control inflammation and bone resorption are needed. We have previously shown that celastrol is a candidate for RA treatment. We have observed that it inhibits both interleukin (IL)-1ß and tumor necrosis factor (TNF) in vitro, and that it has anti-inflammatory properties and ability to decrease synovial CD68+ macrophages in vivo. Herein our goal was to evaluate the effect of celastrol in local and systemic bone loss. METHODS: Celastrol was administrated intraperitoneally at a dose of 1 µg/g/day to female Wistar adjuvant-induced arthritic rats. Rats were sacrificed after 22 days of disease progression, and blood, femurs, tibiae and paw samples were collected for bone remodelling markers quantification, 3-point bending test, micro-CT analysis, nanoindentation and Fourier transform infrared spectroscopy measurements, and immunohistochemical evaluation. RESULTS: We have observed that celastrol preserved articular structures and decreased the number of osteoclasts and osteoblasts present in arthritic joints. Moreover, celastrol reduced tartrate-resistant acid phosphatase 5b, procollagen type 1 amino-terminal propeptide and C terminal crosslinked telopeptide of type II collagen serum levels. Importantly, celastrol prevented bone loss and bone microarchitecture degradation. Celastrol also preserved bone nanoproperties and mineral content. Additionally, animals treated with celastrol had less fragile bones, as depicted by an increase in maximum load and yield displacement. CONCLUSIONS: These results suggest that celastrol reduces both bone resorption and cartilage degradation, and preserves bone structural properties.

Síndrome del apex orbitario postraumático / Orbital apex post-traumatic síndrome

Introducción y Objetivo. El síndrome del ápex orbitario (SAO) es un cuadro grave pero afortunadamente poco frecuente que implica un compromiso de la órbita con afectación del nervio óptico en el ápex. El diagnóstico suele ser difícil y el tratamiento complejo, debiendo incluir medidas de soporte y protección ocular, medicamentos endovenosos como diuréticos y/o corticoides, y en algunos casos llega a necesitar descompresión quirúrgica precoz. El pronóstico depende del tipo y complejidad de la lesión pero también de la precocidad con que se inicie el tratamiento médico o quirúrgico para evitar lesiones irreversibles de las estructuras intraorbitarias derivadas del aumento de la presión en el compartimento. Este trabajo pretende evaluar los casos de síndrome del ápex orbitario postraumático diagnosticados y tratados en nuestro centro hospitalario. Material y Método. Llevamos a cabo una revisión retrospectiva de las bases de datos. Describimos el diagnóstico clínico y por imagen, el tratamiento realizado, las diversas formas de evolución de los pacientes y las secuelas. Resultados. Encontramos y evaluamos un total de 3 casos registrados entre 2007 y 2013, con edades entre 28 y 72 años; 2 hombres y 1 mujer. El origen del síndrome fue un traumatismo de alta energía sobre la región orbitaria/ malar de la cara en todos los casos. Un paciente no precisó tratamiento quirúrgico urgente y los otros 2 necesitaron tratamiento quirúrgico precoz. En 2 casos no se documentaron secuelas permanentes, sin embargo 1 desarrolló ceguera irreversible. Conclusiones. El SAO es una entidad proco frecuente relacionada con traumatismos faciales de alta energía. Su sospecha diagnóstica es indispensable para el enfoque adecuado del tratamiento y suele estar apoyada por medios radiológicos disponibles en cualquier hospital. El tratamiento debe ser precoz para evitar secuelas permanentes; debe incluir estabilización del paciente garantizando la permeabilidad de la vía aérea, corticoides a altas dosis, antibióticos profilácticos y cirugía de revisión de la órbita, que puede ser diagnóstico-terapéutica en casos de oftalmoplejia total con exoftalmos progresivo (AU)

Background and Objective. Orbital apex syndrome (OAS) is a serious and infrequent condition affecting the orbit with involvement of the optic nerve at the apex level. Diagnosis is often difficult and complex. Treatment includes supportive measures and eye protection, intravenous medications such as diuretics and/or corticosteroids and in some cases early surgical decompression is necessary. The prognosis will depend of the type and complexity of the lesion, but also on the precocity of medical or surgical treatment to avoid the irreversible damage of the intraorbital structures, derived from the increase of the pressure inside the compartment. This paper aims to retrospectively review the cases of post-traumatic orbital apex syndrome diagnosed and treated in our hospital. Methods. We conduct a retrospective review of our data base and describe the clinical and imaging diagnosis, the treatments performed, the different forms of evolution and the sequel of this syndrome. Results. Three cases were registered and evaluated between 2007 and 2013. The ages of the patients ranged from 28 to 72 years; 2 men and 1 woman. The origin of the syndrome was in all cases high energy trauma on the orbital/ malar region of the face. One patient did not require urgent surgical treatment, but the other 2 cases required early surgical treatment. In 2 cases no permanent sequel was documented, however 1 of them remained with irreversible blindness. Conclusions. OAS is an infrequent entity related to high energy facial trauma. Diagnostic suspicion is essential for an adequate approach to treatment and is usually supported by radiological means available at any hospital. Treatment should be done early to avoid the permanent consequences. This should include stabilization of the patient ensuring airway permeability, highdose corticosteroids, prophylactic antibiotics and orbital revision surgery, which may be diagnostic-therapeutic in cases of total ophthalmoplegia with progressive exophthalmos (AU)

Influencia de la neuropsiquiatría española en la medicina inverosímil de Ramón Gómez de la Serna / The influence of Spanish neuropsychiatry on the improbable medicine of Ramón Gómez de la Serna

Introducción. El doctor inverosímil es una novela de Ramón Gómez de la Serna (1888-1963) donde seguimos, a través de diversos casos clínicos, las andanzas del doctor Vivar. Objetivo. Presentar y discutir, por primera vez, el influjo que tuvo la neuropsiquiatría española en esta novela, tomando como modelos de estudio los siguientes relatos: Casos cerebrales y La risita. Desarrollo. En este par de relatos, el doctor inverosímil encarna los tres elementos definitorios de la neuropsiquiatría española. En sus repeticiones de la enfermedad de Alzheimer (o en la forma en que se refiere a la parálisis general progresiva) insinúa su orientación germánica. El componente mixto neuropsiquiátrico está ejemplificado en su destreza tanto neurológica (La risita) como psiquiátrica (Casos cerebrales). La afinidad histopatológica del doctor Vivar es evidente en su amplio y oportuno uso de la terminología neurohistológica, principalmente la cajaliana. Conclusiones. Es válido deducir que hay una influencia notoria de la escuela neuropsiquiátrica española en El doctor inverosímil de Gómez de la Serna (AU)

Introduction. El doctor inverosímil (The Improbable Doctor) is a novel by Ramón Gómez de la Serna (1888-1963) in which the reader follows, by means of a series of different clinical cases, the adventures of Doctor Vivar. AIMS. To present and discuss, for the first time, the influence that Spanish neuropsychiatry had on this novel, taking the following short stories as study models: Casos cerebrales (Brain Cases) and La risita (The Giggles). DEVELOPMENT. In these two tales, the improbable doctor embodies the three defining elements of Spanish neuropsychiatry. The repetitions of Alzheimers disease (or in the way in which progressive general paralysis is referred to) hints at its Germanic orientation. The mixed neuropsychiatric component is exemplified in both his neurological (La risita) and psychiatric skills Casos cerebrales). Doctor Vivars affinity to things histopathological is apparent in his wide and timely usage of neurohistological terminology, mainly from Cajal. Conclusions. It can be deduced that the Spanish neuropsychiatric school had a strong influence on Gómez de la Serna’s El doctor inverosímil (AU)

Two kinds of apoplexy in the Colonial press. / Dos clases de apoplejía en la prensa novohispana.

In 1787, three Colonial physicians quoted from Le Clerc (1726-1798) in the Gazeta de México. The French author lists six specific cases where bloodletting is often fatal, including two kinds of apoplexy: the serous and the lacteal. Both conditions are nowadays unknown to the majority of specialists in clinical neurology, and we therefore conducted an historical review of these conditions.

[On Alexander's pneumothorax: A critical appraisal]. / El neumotórax de Alejandro Magno: una apreciación crítica.

According to the testimony of Ptolemy, which we know through Arrian, it has been assumed that Alexander the Great suffered a pneumothorax during his campaign against the Malli. In general, this assumption has been interpreted as a historical fact in medical literature. We consulted the same sources and concluded that it is unlikely that Alexander's arrow wound had given him a pneumothorax. In addition, we stressed the extra-historical content of classical sources.

¿Qué se entiende por extremidades y miembros?, ¿existe el reflejo axonal?. Réplica / What do we understand by extremities and limbs? Does the axonal reflex exist?. Reply

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Does salt addiction exist? / ¿Existe la adicción a la sal?

Abstract: BACKGROUND: Salt consumption activates the brain reward system, inducing cravings and the search for salted food. Its excessive intake is associated with high blood pressure and obesity. The high quantity of salt in processed food is most likely a major cause of the global pandemic of hypertension (HT). OBJECTIVE: To review the current information on the topic of salt addiction and the health consequences this has. METHOD: A search in PubMed, ScienceDirect, and EBSCOhost databases was conducted with the keywords "salt", "salt addiction", and "food addiction". Articles with information relative to the topic of interest were checked, as were references of those articles and historical and culturally complementary information. RESULTS: We described the historical relationship between man and salt, the physiology of salty taste perception, its role in the reward system and the health consequences of a high sodium diet. DISCUSSION AND CONCLUSION: There is physiological and behavioural evidence that some people may develop a true addiction to food. Among these people, salt addiction seems to be of great importance in the development of obesity, HT and other diseases. Sodium is present in high quantities in processed food as salt and monosodium glutamate (MSG), used as flavour enhancers and food preservatives, including in non-salty foods like bread and soft drinks.

Resumen: ANTECEDENTES: El consumo de sal activa el sistema de recompensa cerebral, induciendo el deseo y búsqueda de alimentos salados. Su ingesta excesiva se asocia a presión arterial elevada y obesidad. La gran cantidad de sal en los alimentos procesados ha permitido que la hipertensión (HT) se instale hoy día como una pandemia. OBJETIVO: Revisar la bibliografía existente en el tema de adicción a la sal y sus consecuencias en la salud. MÉTODO: Se realizó una búsqueda en bases de datos PubMed, EBSCOhost y ScienceDirect con las palabras claves "salt", "salt addiction", "food addiction"; se revisaron los artículos que contuvieran información relativa al tema de interés así como referencias en estos mismos artículos e información histórica y cultural complementaria. RESULTADOS: Describimos la relación histórica entre el hombre y la sal, los mecanismos fisiológicos de percepción del sabor salado, su acción sobre el sistema de recompensa y las consecuencias en la salud de una dieta alta en sodio. DISCUSIÓN Y CONCLUSIÓN: Existe evidencia fisiológica y comportamental de que las personas pueden desarrollar una verdadera adicción a la ingestión de alimentos. Entre estas personas la adición a la sal juega un papel muy importante para el desarrollo de obesidad, hipertensión y otras enfermedades. El sodio está presente en altas cantidades en los alimentos procesados en forma de sal y glutamato monosódico (MSG), usados como conservadores o aditivos alimentarios, incluso en alimentos no salados como harinas y refrescos dulces.

Las dos caras del reflejo venoarteriolar: vasoconstricción y vasodilatación cutánea al bajar y subir el brazo / The two faces of veno-arteriolar reflex: cutaneous vasodilatation and vasoconstriction to raise and to lower the arm

Introducción. El reflejo venoarteriolar (RVA) lo provoca un incremento en la presión venosa transmural al colocar una parte del cuerpo en el sentido de la aceleración gravitatoria por debajo del corazón. Objetivo. Evaluar el RVA en sujetos sanos al levantar una parte del cuerpo por encima del corazón. Sujetos y métodos. En 16 sujetos sanos (20-65 años) se estudió el RVA mediante cambios en el flujo sanguíneo de la piel con un fotopletismógrafo digital infrarrojo colocado en el pulpejo en sujetos sanos durante las siguientes condiciones: brazo derecho a la altura del corazón, brazo derecho 40 cm por debajo del corazón y brazo derecho 40 cm por encima del corazón. Las variables medidas fueron: amplitud del flujo sanguíneo de la piel con el brazo a la altura del corazón (amplitud basal), porcentaje de disminución del flujo sanguíneo de la piel con el brazo por debajo del corazón y porcentaje de aumento del flujo sanguíneo de la piel con el brazo por encima del corazón. Resultados. El porcentaje de vasoconstricción con el brazo derecho por debajo del corazón fue del 35%, y el de vasodilatación, del 50%. Conclusiones. La evaluación del RVA con el brazo por debajo del corazón provoca vasoconstricción, y la elevación del brazo produce una importante vasodilatación. La vasoconstricción y la vasodilatación se mantienen mientras la extremidad se mantenga por encima o por debajo del corazón. Éste es un estudio potencialmente muy útil y económico para estudiar la inervación de la microcirculación en diversas neuropatías periféricas de fibras delgadas y mixtas (AU)

Introduction. The veno-arteriolar reflex (VAR) is triggered by an increase in the transmural venous pressure on placing a part of the body in the same direction as the gravitational acceleration below the heart. Aim. To assess the VAR in healthy subjects on raising a part of the body above the level of the heart. Subjects and methods. VAR was studied in 16 healthy subjects (20-65 years old) by means of changes in the blood flow in the skin detected using a digital infrared photoplethysmograph attached to the fingertip under the following conditions: right arm at the height of the heart, right arm below the heart and right arm below the level of the heart. The variables measured were: amplitude of the blood flow in the skin with the arm raised to the height of the heart (baseline amplitude), percentage decrease of the blood flow in the skin with the arm below the heart and percentage increase in blood flow with the arm above the heart. Results. The percentage of vasoconstriction with the right arm below the heart was 35%, and that of vasodilation, 50%. Conclusions. Evaluation of the VAR with the arm below the heart causes vasoconstriction, and elevation of the arm causes an important degree of vasodilation. Vasoconstriction and vasodilation are maintained while the limb is kept above or below the heart. This is an economical and potentially very useful way of studying the innervation of the microcirculation in a number of different peripheral neuropathies of thin and mixed fibres (AU)