Thiamine insufficiency induces Hypoxia Inducible Factor-1α as an upstream mediator for neurotoxicity and AD-like pathology.

Insufficiencies of the micronutrient thiamine (Vitamin B1) have been associated with inducing Alzheimer's disease (AD)-like neuropathology. The hypometabolic state associated with chronic thiamine insufficiency (TI) has been demonstrated to be a contributor towards the development of amyloid plaque deposition and neurotoxicity. However, the molecular mechanism underlying TI induced AD pathology is still unresolved. Previously, we have established that TI stabilizes the metabolic stress transcriptional factor, Hypoxia Inducible Factor-1α (HIF1α). Utilizing neuronal hippocampal cells (HT22), TI-induced HIF1α activation triggered the amyloidogenic cascade through transcriptional expression and increased activity of ß-secretase (BACE1). Knockdown and pharmacological inhibition of HIF1α during TI significantly reduced BACE1 and C-terminal Fragment of 99 amino acids (C99) formation. TI also increased the expression of the HIF1α regulated pro-apoptotic protein, BCL2/adenovirus E1B 19 kDa protein-interacting protein (BNIP3). Correspondingly, cell toxicity during TI conditions was significantly reduced with HIF1α and BNIP3 knockdown. The role of BNIP3 in TI-mediated toxicity was further highlighted by localization of dimeric BNIP3 into the mitochondria and nuclear accumulation of Endonuclease G. Subsequently, TI decreased mitochondrial membrane potential and enhanced chromatin fragmentation. However, cell toxicity via the HIF1α/BNIP3 cascade required TI induced oxidative stress. HIF1α, BACE1 and BNIP3 expression was induced in 3xTg-AD mice after TI and administration with the HIF1α inhibitor YC1 significantly attenuated HIF1α and target genes levels in vivo. Overall, these findings demonstrate a critical stress response during TI involving the induction of HIF1α transcriptional activity that directly promotes neurotoxicity and AD-like pathology.

[Informed consent in shared processes]. / Consentimiento informado en procesos compartidos.

Nowadays, medicine tends towards specialization. But there are also more shared or interdisciplinary processes in which professionals request some type of technique or a diagnostic or therapeutic procedure that must performed by another specialist. In this scenario that involves different professionals, it is reasonable a certain debate about which of them should obtain the informed consent of the patient. The first error would be to pose this process as a confrontation between professionals who derive or delegate their own responsibilities to another. It is, on the contrary, a teamwork and not a mere delegation of duties. On the one hand, it should be the doctor who carries out the technique and, therefore, knows it best as a procedure and is an expert in the early diagnosis and management of side effects, who should inform about the procedure and its risks. And, therefore, it is his duty to obtain the appropriate informed consent. And, since everything is understood as a shared process, it would also be advisable that the physician in charge of the care and follow-up of the patient, and who has taken the initiative to request this technique, had already provided basic information, more focused on the reason for the indication, and that a pre-consent had been obtained, that is a prior elementary verbal consent of acceptance or, at least, of non-rejection. And it would be convenient to record this information in the medical record as well.

Consentimiento informado en procesos compartidos / Informed consent in shared processes

La medicina actual tiende a la especialización. Pero también cada vez son más frecuentes los procesoscompartidos o interdisciplinares en que un profesional solicita algún tipo de técnica o un procedimientodiagnóstico o terapéutico que debe realizar otro especialista. En un escenario así, que implica a profesio-nales diferentes, es razonable que surja cierto debate sobre a cuál de ellos le correspondería obtener elconsentimiento informado por parte del paciente. El primer error sería plantear este proceso como un en-frentamiento entre profesionales que derivan o delegan en otro sus propias responsabilidades. Al contra-rio, es preciso entenderlo como de un trabajo en equipo y no como una mera delegación de compromisos.Por una parte, sigue siendo el médico que lleva a cabo la técnica y que, por tanto, mejor la conoce comoprocedimiento y que es experto en la detección precoz y en el manejo de los efectos secundarios, el que de-bería asumir el compromiso de informar sobre este procedimiento y sus perfiles específicos. Y, por ello, esa él a quien le corresponde obtener el oportuno consentimiento informado. Por otra, al entenderlo comoun proceso compartido, lo adecuado sería que el médico responsable del seguimiento del paciente y quees quien ha tomado la iniciativa de solicitar esta técnica hubiese aportado una información elemental, máscentrada en el motivo de la indicación, y que con ello se hubiese obtenido un preconsentimiento, es deciruna aceptación básica o, al menos, un no-rechazo previo a la técnica. Y sería conveniente dejar registro deesta información en la historia clínica.(AU)

Nowadays, medicine tends towards specialization. But there are also more shared or interdisciplinaryprocesses in which professionals request some type of technique or a diagnostic or therapeutic procedurethat must performed by another specialist. In this scenario that involves different professionals, it is reaso-nable a certain debate about which of them should obtain the informed consent of the patient. The firsterror would be to pose this process as a confrontation between professionals who derive or delegate theirown responsibilities to another. It is, on the contrary, a teamwork and not a mere delegation of duties. Onthe one hand, it should be the doctor who carries out the technique and, therefore, knows it best as a pro-cedure and is an expert in the early diagnosis and management of side effects, who should inform about the procedure and its risks. And, therefore, it is his duty to obtain the appropriate informed consent. And,since everything is understood as a shared process, it would also be advisable that the physician in chargeof the care and follow-up of the patient, and who has taken the initiative to request this technique, hadalready provided basic information, more focused on the reason for the indication, and that a pre-consenthad been obtained, that is a prior elementary verbal consent of acceptance or, at least, of non-rejection.And it would be convenient to record this information in the medical record as well.(AU)

¿El 20 % de los pacientes oncológicos fallece por caquexia? / Do 20 % of cancer patients die from cachexia?

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Crisis de opioides: ¿nos afecta? / Opioid crisis: does it affect us?

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Diplopia en un paciente con cáncer de próstata avanzado / Diplopia in a patient with advanced prostate cancer

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Los últimos románticos... / The last of the romantics...

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Revistas de acceso abierto y voracidad editorial en cuidados paliativos / Open access journals and predatory publishing in palliative care

OBJETIVO: Las revistas de acceso abierto han aumentado en los últimos años en todos los ámbitos de la medicina. Una corrupción de este acceso abierto es lo que se ha llamado voracidad editorial (predatory publishing). Pretendemos conocer qué revistas del ámbito de cuidados paliativos están disponibles en acceso abierto y saber si pueden tener perfil de voracidad editorial. MÉTODO: Búsqueda de revistas sobre cuidados paliativos en acceso abierto en buscadores online, registros de revistas y correos electrónicos recibidos de estas publicaciones. Variables registradas: nombre, editorial y página web de la revista, perfil del pago, inclusión en lista de Beall, registro e indexación, correos electrónicos solicitando trabajos, posibilidad de optar a revisor o comité editorial. RESULTADOS: Se encontraron 32 revistas del ámbito de cuidados paliativos con opción total o parcial de acceso abierto; tres de ellas no se encontraban activas. La mediana de coste por publicación de un trabajo original fue de 1.389€. Se encontraron tres perfiles de publicación: nueve revistas de editoriales reconocidas, indexadas e incluso con factor de impacto que admiten la posibilidad de publicar con acceso abierto; siete revistas de editoriales de perfil académico (open access scholarly), algunas indexadas y con factor de impacto, que solo publican con acceso abierto, y 16 revistas sospechosas de voracidad editorial. Encontramos asociación entre la presencia en la lista de Beall y algunos criterios de sospecha de voracidad editorial: ausencia de factor de impacto (p = 0,004) o de indexación en PubMed (p = 0,001); ausencia de registro en OASPA (p = 0,001); envío de correos electrónicos solicitando trabajos (p = 0,05); opción de pago único por periodo de tiempo (p = 0,02), y flexibilidad en el pago según tipo de artículo (p = 0,02). CONCLUSIONES: En el ámbito de los cuidados paliativos hay publicaciones de acceso abierto, algunas de ellas sospechosas de ser voracidad editorial

OBJECTIVE: Open access journals have increased in recent years in all areas of medicine. Predatory publishing is corrupting this open access. The objective of this study is to find out the medical journals that are available in open access in the field of Palliative Care and establish whether they could have a predatory publishing profile. Method: Online search with Google and Bing, and a search in open access journal registries, and e-mails from open access Palliative Care journals. Registered variables: name, editorial and website of the journal, payment profile, inclusion in Beall's list register and indexation, e-mails requesting articles, and possibility to become reviewer or editorial committee. RESULTS: We found 32 journals in the field of Palliative Care with full or partial open access option; three of them were not active. The median original publication fee was 1389€. Globally, three types of journal could be distinguished: 9 journals of recognized publishers, indexed and even with impact factor, that allow the possibility of publishing with open access; 7 open access scholarly journals, some indexed and with impact factor, that only publish open access, and 16 suspected predatory journals. We found an association between the presence of the journal on Beall's list and some suspicion criteria for predatory publishing such as: absence of impact factor (P=.004) or PubMed indexation (P=.001); no OASPA registration (P=.001); e-mails requesting works (P=.05); option of payment per time period (P=.02); and flexibility in payment according to type of article (P=.02). CONCLUSIONS: In the field of Palliative Care there open access publications, however some of them are suspected predatory publishing

¿Qué fármacos se pueden retirar en el enfermo avanzado? / What drugs can be withdrawn in advanced patients?

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¿Es diferente el pronóstico del glioblastoma multiforme y de las metástasis cerebrales? / Are there differences in the prognosis of glioblastoma multiforme and brain metastases?

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La intensidad de la atención y el alivio de síntomas / Intensity of patient care and symptom relief

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La paradoja de las interacciones medicamentosas en cuidados paliativos / The paradox of drug interactions in palliative care

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Comentario sobre "Reflexiones acerca de la eutanasia en Colombia" / Commentary on "Reflections about euthanasia in Colombia"

We have read with great interest the Reflections about euthanasia in Colombia. It has reminded us that the support to decriminalize euthanasia is usually based on ordinary arguments: an emotional appeal of someone else's pain, rejection of disproportionate therapies, and praise to the autonomy of the individual. All of the above are mentioned in the text. With the emotional argument of mitigating pain and suffering to accomplish a smooth and easy transit or the idea of love and feelings of human solidarity with the sufferer, empathy is the logical consequence ("I wouldn't want to go through that") and presume that what is appropriate and piety-deserving is giving the patient an efficient and immediate exit. The rejection we all have against therapeutic obstinacy (cause useless suffering because of failure to adapt the therapy to the patient's situation, prognosis and values) leads to extreme positions that present euthanasia as the only option to avoid and prevent such disproportionate treatments. Finally, this autonomist and individualistic argument, transforms the respect for the right to refuse therapy or choose among several options inherent to lex artis into submission to the patient's wish, imposing his/her will as the only healthcare criterion. Beyond these arguments, when the debate turns into radical positions, the rejection of euthanasia is frequently presented as a religious issue, a Jewish-Christian cultural atavism or a moral imposition in the name of beliefs alien to a secular society.

¿Conspiración del silencio o confabulación en la negación? / Conspiracy of silence or collusion in denial?

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Cómo responder al paciente con cáncer avanzado que nos plantea el uso de cannabis como tratamiento sintomático / How do we respond to an advanced cancer patient asking about cannabis as a symptomatic treatment?

OBJETIVO: Sugerir recomendaciones para ayudar al paciente con cáncer avanzado, o al familiar, que plantea el uso de marihuana u otras formas de cannabis medicinal como tratamiento sintomático o de soporte. MÉTODO: A partir de un ejemplo real, se presenta un resumen de la farmacología de los cannabinoides naturales y sintéticos, de la evidencia sobre su eficacia como tratamiento sintomático en cáncer avanzado, y de la actitud y expectativas del paciente o la familia que plantea el uso medicinal del cannabis. Resultado: El cannabis medicinal contiene más de 60 cannabinoides naturales (de los cuales el delta-9-tetrahidrocannabinol es el más importante) y otras sustancias. En nuestro medio, los pacientes que plantean el empleo de cannabis como tratamiento sintomático no solicitan cannabinoides sintéticos aprobados en otros países sino la hierba de cannabis o sus derivados. Lo suelen consumir fumado (lo que favorece la aparición más temprana de niveles plasmáticos) o en infusión. El consumo de cannabis medicinal se presta a una gran variabilidad en las concentraciones plasmáticas de delta-9-tetrahidrocannabinol. Existen pocos estudios que evalúen científicamente la eficacia del cannabis medicinal en el control de síntomas del paciente con cáncer avanzado. Los estudios realizados con cannabinoides sintéticos son metodológicamente muy limitados, pero aportan cierta evidencia sobre el efecto de los cannabinoides en el alivio del dolor (también como coadyuvante), de las náuseas y de los vómitos inducidos por quimioterapia en el enfermo oncológico. No hay evidencia suficiente para afirmar su eficacia en el tratamiento de la hiporexia. Los efectos secundarios de los cannabinoides en dosis moderadas (como en el uso de cannabis medicinal) son en su mayoría leves y de perfil neuropsicológico. La actitud y las expectativas del paciente, junto con el modo de empleo del cannabis medicinal, pueden favorecer que parte de su beneficio se deba a un efecto placebo. CONCLUSIONES: El cannabis medicinal no parece ser tan activo como esperan los pacientes ni tan tóxico como suponen muchos profesionales. Para responder al paciente con cáncer avanzado que plantea su uso como tratamiento sintomático es aconsejable evitar prejuicios, actuar con respeto y prudencia y buscar el beneficio sintomático del paciente

OBJECTIVE: To contribute ideas to answer advanced cancer patients asking about the use of medicinal cannabis as a symptomatic treatment. Method: Based on a real example, we present a summary of the pharmacology of natural and synthetic cannabinoids, the evidence on its effectiveness as a symptomatic treatment in advanced cancer, and the patient's attitude and expectations raised by the medicinal use of cannabis. RESULT: There are more than 60 different cannabinoids (the most relevant: delta-9-tetrahydrocannabinol) and other substances in cannabis. In our setting, patients who ask about the use of cannabis as a symptomatic treatment do not look for synthetic cannabinoids approved in other countries, but rather prefer herbal cannabis or its derivatives. They usually consume smoked cannabis (favoring the earlier onset of plasma levels) or, rarely, in infusion. Use of medicinal cannabis causes a wide variation in plasma concentrations of delta-9-tetrahydrocannabinol. There is evidence supporting a certain effect of synthetic cannabinoids in pain relief (also as an adjuvant), and as antiemetic for chemotherapy-induced nausea and vomiting in cancer PATIENTS: This evidence is based primarily on results of studies with limited methodological quality. There is insufficient evidence to assert its effectiveness in the treatment of anorexia. Side effects of moderate doses of synthetic cannabinoids or medicinal cannabis are mostly mild, as well as their psycho-neurological profile. The attitude and expectations of the patient, and the way to consume of medical cannabis may favor that part of its benefit may be due to a placebo effect. CONCLUSIONS: Medicinal cannabis does not seem as active as patients expect, or as toxic as many professionals suspect. To respond to the advanced cancer patient asking about their use as symptomatic treatment is advisable to avoid prejudice, to respect and to act with caution seeking the patient's symptomatic Benefit

Cumplimiento estimado de los estándares de calidad propuestos en Cuidados Paliativos dentro de Unidades de Hospitalización de Oncología / Estimated compliance of Oncology Inpatient Units with the quality standards proposed in Palliative Care

Introducción: En 2006 se publicó la propuesta de la SECPAL y el Ministerio de Sanidad y Consumo de indicadores de calidad en Cuidados Paliativos con la proporción de cumplimiento de cada uno que se plantea como referencia. Objetivo: Realizar una estimación del cumplimiento de estos estándares en la atención de enfermos oncológicos avanzados en Unidades de Oncología Médica. Material y métodos: Doce profesionales (oncólogos y enfermeras) de cuatro Unidades de Hospitalización que atienden enfermos de Oncología Médica realizaron una estimación del porcentaje de cumplimiento en su unidad de los 35 indicadores de calidad de la SECPAL. Para cada estándar se calcula la media de las estimaciones y se compara con el estándar recomendado de cumplimiento. Resultados: La media de las estimaciones de cumplimiento se encuentra dentro de los estándares propuestos en nueve (26%) de los 35 indicadores. De los otros 26 indicadores, en 20(77%) la diferencia respecto al estándar superaba el 10%. No se consideró que se alcanzasen los estándares en ninguno de los 16 indicadores que exigían un cumplimiento del100%. La media de cumplimiento fue de 9,5 estándares (límites: 8-12) por hospital. Solo se estimó que cuatro (11%) de los 35 indicadores se cumplían adecuadamente en todos los hospitales (..) (AU)

Introduction: In 2006 the Sociedad Española de Cuidados Paliativos (Spanish Society of Palliative Care, SECPAL) and the Spanish Ministry of Health published a proposal of quality standards on Palliative Care. It included a reference of the proposed acceptable percentage of compliance of these indicators. Many advanced cancer patients are treated in Medical Oncology Units, but there are no data on how these standards are observed in these patients. Objective: To obtain an estimate of the compliance with these standards in the care of advanced cancer patients admitted to Medical Oncology Units. Methods: Six oncologists and six nurses from four different Medical Oncology Units gave an estimate of the compliance rate of the 35 quality indicators proposed by SECPAL. For each standard, the mean of the estimations was compared with the recommended standard of compliance. Results: The mean estimates of compliance is within the proposed standards in nine (26%) of the35 indicators. On the remaining 26 indicators, in 20 (77%) the difference between the estimated value and the reference rate was above 10%. No indicator that required 100% compliance was considered achieved. In every Hospital a mean of 9.5 standards (range: 8 to 12) were fulfilled. Only in four (11%) indicators were the estimations entered within standards in all the four (..) (AU)

[The Alliance for the Prevention of Colorectal Cancer in Spain. A civil commitment to society]. / Alianza para la Prevención del Cáncer de Colon en España: un compromiso cívico con la sociedad.

Colorectal cancer (CRC) is the most common malignant tumor in Spain, when men and women are considered together, and the second leading cause of cancer death. Every week in Spain over 500 cases of CRC are diagnosed, and nearly 260 people die from the disease. Epidemiologic estimations for the coming years show a significant increase in the number of annual cases. CRC is a perfectly preventable tumor and can be cured in 90% of cases if detected in the early stages. Population-based screening programs have been shown to reduce the incidence of CRC and mortality from the disease. Unless early detection programs are established in Spain, it is estimated that in the coming years, 1 out of 20 men and 1 out of 30 women will develop CRC before the age of 75. The Alliance for the Prevention of Colorectal Cancer in Spain is an independent and non-profit organization created in 2008 that integrates patients' associations, altruistic non-governmental organizations and scientific societies. Its main objective is to raise awareness and disseminate information on the social and healthcare importance of CRC in Spain and to promote screening measures, early detection and prevention programs. Health professionals, scientific societies, healthcare institutions and civil society should be sensitized to this highly important health problem that requires the participation of all sectors of society. The early detection of CRC is an issue that affects the whole of society and therefore it is imperative for all sectors to work together.