Chronic phase advances reduces recognition memory and increases vascular cognitive dementia-like impairments in aged mice.

Disrupted or atypical light-dark cycles disrupts synchronization of endogenous circadian clocks to the external environment; extensive circadian rhythm desynchrony promotes adverse health outcomes. Previous studies suggest that disrupted circadian rhythms promote neuroinflammation and neuronal damage post-ischemia in otherwise healthy mice, however, few studies to date have evaluated these health risks with aging. Because most strokes occur in aged individuals, we sought to identify whether, in addition to being a risk factor for poor ischemic outcome, circadian rhythm disruption can increase risk for vascular cognitive impairment and dementia (VCID). We hypothesized that repeated 6 h phase advances (chronic jet lag; CJL) for 8 weeks alters cerebrovascular architecture leading to increased cognitive impairments in aged mice. Female CJL mice displayed impaired spatial processing during a spontaneous alternation task and reduced acquisition during auditory-cued associative learning. Male CJL mice displayed impaired retention of the auditory-cued associative learning task 24 h following acquisition. CJL increased vascular tortuosity in the isocortex, associated with increased risk for vascular disease. These results demonstrate that CJL increased sex-specific cognitive impairments coinciding with structural changes to vasculature in the brain. We highlight that CJL may accelerate aged-related functional decline and could be a crucial target against disease progression.

LIFT procedure: postoperative outcomes, risk factors for fistula recurrence and continence impairment.

Ligation of the intersphincteric fistula tract has been recently employed as definitive treatment of anal fistulas. However, it carries a potential risk of continence impairment, fistula recurrence, and repeated operations. This study aimed to assess postoperative outcomes related to this procedure and evaluate the potential influence of preoperative and intraoperative features. Patients who underwent LIFT procedure between June 2012 and September 2021 were retrospectively analyzed. Patients were divided according to whether they developed fistula recurrence and on the history of a surgery prior to the LIFT. Preoperative features, postoperative outcomes, and risk factors adverse outcomes were analyzed. Forty-eight patients were included, of which 25 received primary LIFT, being the high transsphincteric fistula pattern the most frequent (62.5%). The median follow-up was 13.3 months, with a recurrence rate of 20.8%, of which the majority presented an intersphincteric fistula pattern (50%); and continence impairment rate of 16.7%. A higher prevalence of diabetes (p = 0.026) and a trend towards a higher prevalence of patients with a history of high transsphincteric fistula (0.052) were observed in the group with fistula recurrence. The history of diabetes and the operation time with a cut-off value ≥ 69 min showed a trend as a risk factors for developing fistula recurrence (0.06) and postoperative continence impairment (0.07), respectively. The LIFT procedure seems to be safe in terms of morbidity, with a reasonable incidence of recurrences, showing better results when it is primarily performed. Preoperative characteristics should be considered as they may impact outcomes.

Social enrichment alters the response of brain leukocytes to chemotherapy and tumor development in aged mice.

Aging is a risk factor for the development of breast cancer. Foundational science studies have supported associations among neuroinflammation, breast cancer, and chemotherapy, but to date, these associations are based on studies using young adult rodents. The current study examined the neuroinflammatory effects of chemotherapy in aged, tumor-naïve and tumor-bearing mice with or without social enrichment. Mice received two intravenous injections of doxorubicin (A) and cyclophosphamide (C) at a two-week interval. Brain immune cells were enriched/assessed via flow cytometry, seven days following the second chemotherapy injection. Social enrichment enhanced peripheral immune cell trafficking in aged tumor-naive mice treated with AC. Group housed aged tumor bearing mice receiving AC had reduced percentage of IL-6+ monocytes and granulocytes relative to their singly housed counterparts. Notably, group housing aged experimental mice with young cage partners significantly reduced TNF + monocytes, tumor volume, and tumor mass. These data illustrate the importance of social enrichment in attenuating neuroinflammation and are the first to demonstrate that social support with young housing partners reduces tumor growth in aged mice.

The Mexican consensus on fecal incontinence.

Fecal incontinence is the involuntary passage or the incapacity to control the release of fecal matter through the anus. It is a condition that significantly impairs quality of life in those that suffer from it, given that it affects body image, self-esteem, and interferes with everyday activities, in turn, favoring social isolation. There are no guidelines or consensus in Mexico on the topic, and so the Asociación Mexicana de Gastroenterología brought together a multidisciplinary group (gastroenterologists, neurogastroenterologists, and surgeons) to carry out the «Mexican consensus on fecal incontinence¼ and establish useful recommendations for the medical community. The present document presents the formulated recommendations in 35 statements. Fecal incontinence is known to be a frequent entity whose incidence increases as individuals age, but one that is under-recognized. The pathophysiology of incontinence is complex and multifactorial, and in most cases, there is more than one associated risk factor. Even though there is no diagnostic gold standard, the combination of tests that evaluate structure (endoanal ultrasound) and function (anorectal manometry) should be recommended in all cases. Treatment should also be multidisciplinary and general measures and drugs (lidamidine, loperamide) are recommended, as well as non-pharmacologic interventions, such as biofeedback therapy, in selected cases. Likewise, surgical treatment should be offered to selected patients and performed by experts.

XV Reunión Post-ECTRIMS: revisión de las novedades presentadas en el Congreso ECTRIMS 2022 (I) / 15th Post-ECTRIMS Meeting: a review of the latest developments presented at the 2022 ECTRIMS Congress (Part I)

Introducción: El 4 y el 5 de noviembre se celebró en Madrid la XV edición de la Reunión Post-ECTRIMS, donde neurólogos expertos en esclerosis múltiple (EM) resumieron las principales novedades presentadas en el congreso de ECTRIMS 2022, celebrado en Ámsterdam entre el 26 y el 28 de octubre. Objetivo: Sintetizar las ponencias que tuvieron lugar en la Reunión Post-ECTRIMS, en un artículo desglosado en dos partes. Desarrollo: En esta primera parte se presentan los primeros eventos involucrados en el inicio de la EM, la implicación de los linfocitos y la migración de células del sistema inmunitario hacia el sistema nervioso central. Se describen los biomarcadores emergentes en fluidos corporales y los hallazgos de imagen que permiten predecir la evolución de la enfermedad, y que resultan útiles en el diagnóstico diferencial de la EM. También se exponen los avances en las técnicas de imagen que, junto con un mayor conocimiento de los agentes involucrados en los procesos de desmielinización y remielinización, proporcionan una base para abordar la remielinización en el entorno clínico. Por último, se repasan los mecanismos desencadenantes de la reacción inflamatoria y la neurodegeneración implicados en la patología de la EM.(AU)

Introduction: On 4 and 5 November 2022, Madrid hosted the 15th edition of the Post-ECTRIMS Meeting, where neurologists specialised in multiple sclerosis (MS) outlined the most relevant novelties presented at the 2022 ECTRIMS Congress, held in Amsterdam from 26 to 28 October. Aim: To synthesise the content presented at the 15th edition of the Post-ECTRIMS Meeting, in an article broken down into two parts. Development: In this first part, the initial events involved in the onset of MS, the role played by lymphocytes and the migration of immune system cells into the central nervous system are presented. It describes emerging biomarkers in body fluids and imaging findings that are predictive of disease progression and useful in the differential diagnosis of MS. It also discusses advances in imaging techniques which, together with a better understanding of the agents involved in demyelination and remyelination processes, provide a basis for dealing with remyelination in the clinical setting. Finally, the mechanisms triggering the inflammatory reaction and neurodegeneration involved in MS pathology are reviewed.(AU)

XV Reunión Post-ECTRIMS: revisión de las novedades presentadas en el Congreso ECTRIMS 2022 (II) / 15th Post-ECTRIMS Meeting: a review of the latest developments presented at the 2022 ECTRIMS Congress (Part II)

Introducción: El 4 y el 5 de noviembre se celebró en Madrid la Reunión Post-ECTRIMS, en la que neurólogos expertos en esclerosis múltiple resumieron las principales novedades presentadas en el congreso de ECTRIMS 2022, celebrado entre el 26 y el 28 de octubre en Ámsterdam. Objetivo: Sintetizar las ponencias que tuvieron lugar en la Reunión Post-ECTRIMS, en un artículo desglosado en dos partes. Desarrollo: En esta segunda parte, se presentan las novedades sobre las estrategias terapéuticas de escalado y desescalado de los tratamientos modificadores de la enfermedad (TME), cuándo y a quién iniciar o cambiar a TME de alta eficacia, la definición de fracaso terapéutico, la posibilidad de tratar el síndrome radiológico asilado, el futuro del tratamiento personalizado y la medicina de precisión, la eficacia y seguridad del autotrasplante de células madre hematopoyéticas, diferentes aproximaciones en el diseño de ensayos clínicos y en las medidas de resultados para evaluar TME en fases progresivas, retos en el diagnóstico y tratamiento del deterioro cognitivo, y tratamiento en situaciones especiales (embarazo, comorbilidad y personas mayores). Además, se muestran los resultados de algunos de los últimos estudios realizados con cladribina oral y evobrutinib presentados en el ECTRIMS 2022.(AU)

Introduction: On 4 and 5 November 2022, Madrid hosted the 15th edition of the Post-ECTRIMS Meeting, where neurologists specialised in multiple sclerosis outlined the latest developments presented at the 2022 ECTRIMS Congress, held in Amsterdam from 26 to 28 October. Aim: To synthesise the content presented at the 15th edition of the Post-ECTRIMS Meeting, in an article broken down into two parts. Development: This second part describes the new developments in terms of therapeutic strategies for escalation and de-escalation of disease-modifying therapies (DMT), when and in whom to initiate or switch to highly effective DMT, the definition of therapeutic failure, the possibility of treating radiologically isolated syndrome and the future of personalised treatment and precision medicine. It also considers the efficacy and safety of autologous haematopoietic stem cell transplantation, different approaches in clinical trial design and outcome measures to assess DMT in progressive stages, challenges in the diagnosis and treatment of cognitive impairment, and treatment in special situations (pregnancy, comorbidity and the elderly). In addition, results from some of the latest studies with oral cladribine and evobrutinib presented at ECTRIMS 2022 are shown.(AU)

Tumor fibroso pleural ¿son realmente benignos? ¿Cuándo deben operarse? / Pleural fibrous tumor, are they really benign? When should they have operation?

El tumor fibroso pleural es un tumor habitualmente asintomático, benigno y de lento crecimiento, que en un pequeño porcentaje de los casos tiene un comportamiento más agresivo. Para definir los criterios de malignidad es necesario un análisis inmunohistoquímico. El tratamiento de elección es la resección quirúrgica completa con márgenes de seguridad ya sea por toracotomía o por videotoracoscopia en función del tamaño. Se encuentra en estudio la utilización de terapia adyuvante radioterápica o quimioterápica que en el momento actual no cuenta con resultados significativos. Presentamos dos casos que fueron tratados de forma quirúrgica, con extirpación completa siendo el primero definido como maligno según los criterios histológicos y el segundo benigno, pero de alto riesgo. Solo uno de ellos recibió terapia adyuvante. (AU)

Solitary fibrous pleural tumor is a usually asymptomatic, benign and slow-growing tumor, which in a small percentage of cases has a more aggressive behavior. To define the malignancy criteria, an immunohistochemical analysis is necessary. The gold standard treatment is a complete surgical resection with safety margins either by thoracotomy or by videothoracoscopy depending on the size. The use of radiotherapy or chemotherapy as an adjuvant therapy is under study, which at the present time does not have significant results. We present two cases that were treated surgically, with complete removal, one being classified as malignant according to histological criteria and the other benign but high risk. Only one of them received adjuvant therapy. (AU)

Acute exposure to artificial light at night alters hippocampal vascular structure in mice.

The structure and function of the cardiovascular system are modulated across the day by circadian rhythms, making this system susceptible to circadian rhythm disruption. Recent evidence demonstrated that short-term exposure to a pervasive circadian rhythm disruptor, artificial light at night (ALAN), increased inflammation and altered angiogenic transcripts in the hippocampi of mice. Here, we examined the effects of four nights of ALAN exposure on mouse hippocampal vascular networks. To do this, we analyzed 2D and 3D images of hippocampal vasculature and hippocampal transcriptomic profiles of mice exposed to ALAN. ALAN reduced vascular density in the CA1 and CA2/3 of female mice and the dentate gyrus of male mice. Network structure and connectivity were also impaired in the CA2/3 of female mice. These results demonstrate the rapid and potent effects of ALAN on cerebrovascular networks, highlighting the importance of ALAN mitigation in the context of health and cerebrovascular disease.

[15th Post-ECTRIMS Meeting: a review of the latest developments presented at the 2022 ECTRIMS Congress (Part II)]. / XV Reunión Post-ECTRIMS: revisión de las novedades presentadas en el Congreso ECTRIMS 2022 (II).

INTRODUCTION: On 4 and 5 November 2022, Madrid hosted the 15th edition of the Post-ECTRIMS Meeting, where neurologists specialised in multiple sclerosis outlined the latest developments presented at the 2022 ECTRIMS Congress, held in Amsterdam from 26 to 28 October. AIM: To synthesise the content presented at the 15th edition of the Post-ECTRIMS Meeting, in an article broken down into two parts. DEVELOPMENT: This second part describes the new developments in terms of therapeutic strategies for escalation and de-escalation of disease-modifying therapies (DMT), when and in whom to initiate or switch to highly effective DMT, the definition of therapeutic failure, the possibility of treating radiologically isolated syndrome and the future of personalised treatment and precision medicine. It also considers the efficacy and safety of autologous haematopoietic stem cell transplantation, different approaches in clinical trial design and outcome measures to assess DMT in progressive stages, challenges in the diagnosis and treatment of cognitive impairment, and treatment in special situations (pregnancy, comorbidity and the elderly). In addition, results from some of the latest studies with oral cladribine and evobrutinib presented at ECTRIMS 2022 are shown.

TITLE: XV Reunión Post-ECTRIMS: revisión de las novedades presentadas en el Congreso ECTRIMS 2022 (II).Introducción. El 4 y el 5 de noviembre se celebró en Madrid la Reunión Post-ECTRIMS, en la que neurólogos expertos en esclerosis múltiple resumieron las principales novedades presentadas en el congreso de ECTRIMS 2022, celebrado entre el 26 y el 28 de octubre en Ámsterdam. Objetivo. Sintetizar las ponencias que tuvieron lugar en la Reunión Post-ECTRIMS, en un artículo desglosado en dos partes. Desarrollo. En esta segunda parte, se presentan las novedades sobre las estrategias terapéuticas de escalado y desescalado de los tratamientos modificadores de la enfermedad (TME), cuándo y a quién iniciar o cambiar a TME de alta eficacia, la definición de fracaso terapéutico, la posibilidad de tratar el síndrome radiológico asilado, el futuro del tratamiento personalizado y la medicina de precisión, la eficacia y seguridad del autotrasplante de células madre hematopoyéticas, diferentes aproximaciones en el diseño de ensayos clínicos y en las medidas de resultados para evaluar TME en fases progresivas, retos en el diagnóstico y tratamiento del deterioro cognitivo, y tratamiento en situaciones especiales (embarazo, comorbilidad y personas mayores). Además, se muestran los resultados de algunos de los últimos estudios realizados con cladribina oral y evobrutinib presentados en el ECTRIMS 2022.

Hospitalización por reacción adversa a antibiótico. Seguimiento farmacoterapéutico y fisioterapia en el proceso de recuperación / Hospitalization due to an adverse reaction to an antibiotic. Pharmacotherapy and physiotherapy follow-up in the recovery process

Hombre de 34 años que presenta infecciones urológicas recurrentes tratado con diferentes antibióticos como consecuencia de estenosis uretral, se ha sometido a varias intervenciones quirúrgicas desde 2018. Algunos episodios de infección cursan con dolor muy intenso y otros son asintomáticos. En diciembre de 2021 aparece por primera vez fiebre alta, cefalea muy intensa y dolor muscular por lo que se confundieron los síntomas con COVID-19. Cuando aparecieron estos síntomas, el paciente llevaba siendo tratado 8 días con Trimetoprim/sulfametoxazol 160/800 mg. Tras pruebas de COVID-19 negativas, deciden hospitalizar al paciente en urología y determinan que los síntomas se deben a la infección urológica. Le diagnostican además miocarditis y neuropatía periférica. Durante los siguientes meses el paciente vuelve a tener urocultivos positivos para diferentes bacterias y es tratado con otros antibióticos. En mayo de 2022, tras positivo para Escherichia coli le prescriben Trimetoprim/sulfametoxazol 160/800 mg. A los 2 días de iniciar el tratamiento es hospitalizado con fiebre muy alta, cefalea intensa y dolor lumbar y en las extremidades que le impide moverse, es derivado a traumatología y le diagnostican lumbalgia. Durante el segundo ingreso el paciente comenta el caso con su farmacéutica de confianza que conoce su historia clínica desde el inicio y haciendo un estudio se detecta que existe la posibilidad de que los cuadros agudos se deban a un efecto adverso del Trimetoprim/sulfametoxazol 160/800 mg. La farmacéutica notifica al paciente su sospecha que lo traslada a los médicos que lo tratan. Se incluye la información de la posible intolerancia/ alergia en la historia clínica del paciente (AU)

[15th Post-ECTRIMS Meeting: a review of the latest developments presented at the 2022 ECTRIMS Congress (Part I)]. / XV Reunión Post-ECTRIMS: revisión de las novedades presentadas en el Congreso ECTRIMS 2022 (I).

INTRODUCTION: On 4 and 5 November 2022, Madrid hosted the 15th edition of the Post-ECTRIMS Meeting, where neurologists specialised in multiple sclerosis (MS) outlined the most relevant novelties presented at the 2022 ECTRIMS Congress, held in Amsterdam from 26 to 28 October. AIM: To synthesise the content presented at the 15th edition of the Post-ECTRIMS Meeting, in an article broken down into two parts. DEVELOPMENT: In this first part, the initial events involved in the onset of MS, the role played by lymphocytes and the migration of immune system cells into the central nervous system are presented. It describes emerging biomarkers in body fluids and imaging findings that are predictive of disease progression and useful in the differential diagnosis of MS. It also discusses advances in imaging techniques which, together with a better understanding of the agents involved in demyelination and remyelination processes, provide a basis for dealing with remyelination in the clinical setting. Finally, the mechanisms triggering the inflammatory reaction and neurodegeneration involved in MS pathology are reviewed.

TITLE: XV Reunión Post-ECTRIMS: revisión de las novedades presentadas en el Congreso ECTRIMS 2022 (I).Introducción. El 4 y el 5 de noviembre se celebró en Madrid la XV edición de la Reunión Post-ECTRIMS, donde neurólogos expertos en esclerosis múltiple (EM) resumieron las principales novedades presentadas en el congreso de ECTRIMS 2022, celebrado en Ámsterdam entre el 26 y el 28 de octubre. Objetivo. Sintetizar las ponencias que tuvieron lugar en la Reunión Post-ECTRIMS, en un artículo desglosado en dos partes. Desarrollo. En esta primera parte se presentan los primeros eventos involucrados en el inicio de la EM, la implicación de los linfocitos y la migración de células del sistema inmunitario hacia el sistema nervioso central. Se describen los biomarcadores emergentes en fluidos corporales y los hallazgos de imagen que permiten predecir la evolución de la enfermedad, y que resultan útiles en el diagnóstico diferencial de la EM. También se exponen los avances en las técnicas de imagen que, junto con un mayor conocimiento de los agentes involucrados en los procesos de desmielinización y remielinización, proporcionan una base para abordar la remielinización en el entorno clínico. Por último, se repasan los mecanismos desencadenantes de la reacción inflamatoria y la neurodegeneración implicados en la patología de la EM.

The role of daylight exposure on body mass in male mice.

Physiology and behavior are synchronized to the external environment by endogenous circadian rhythms that are set to precisely 24 h by exposure to bright light early in the day. Exposure to artificial light outside of the typical solar day, such as during the night, may impair aspects of physiology and behavior in human and non-human animals. Both the intensity and the wavelength of light are important in mediating these effects. The present report is the result of an unplanned change in our vivarium lighting conditions, which led to the observation that dim light during the daytime affects body mass similarly to dim nighttime light exposure in male Swiss Webster mice. Mice exposed to bright days (≥125 lux) with dark nights (0 lux) gained significantly less weight than those exposed to bright days with dim light at night (5 lux) or dim days (≤60 lux) with either dark nights or dim light at night. Notably, among the mice exposed to dim daytime light, no weight gain differences were observed between dark nights and dim light at night exposure; however dim light at night exposure shifted food intake to the inactive phase as previously reported. The mechanisms mediating these effects remain unspecified, but it appears that dimly illuminated days may have similar adverse metabolic effects as exposure to artificial light at night.

Bronchodilator responsiveness testing with inhaled budesonide/formoterol in asthma.

BACKGROUND: The choice of bronchodilators for responsiveness testing (BRT) is a clinical decision according to ATS/ERS. Since January 2019 we use budesonide/formoterol for BRT in asthma at our center in Argentina. The aim was to compare budesonide/formoterol with salbutamol for BRT in stable asthmatic patients that were followed up in a short-acting beta2 agonist (SABA)-free asthma center. METHODS: From the Hospital database, we found for the same patient at least one BRT using salbutamol 200 µg and another with budesonide/formoterol 320/9 µg. RESULTS: We found similar BRT between salbutamol and budesonide/formoterol in 101 asthmatic individuals (26 males) aged 38.14 ± 16.1 yrs (mean ± Standard deviation). The absolute response was 0.18 ± 0.21 L in FEV1 after salbutamol and 0.20 ± 0.22 L in FEV1 after budesonide/formoterol. Afterwards, we showed 202 patients tested with budesonide/formoterol; the mean absolute response was 0.21 ± 0.22 L in FEV1. There were no unexpected safety findings. CONCLUSIONS: In asthmatic patients, we demonstrated similar efficacy between Budesonide/formoterol and salbutamol for BRT.

Circadian Rhythms Disrupted by Light at Night and Mistimed Food Intake Alter Hormonal Rhythms and Metabolism.

Availability of artificial light and light-emitting devices have altered human temporal life, allowing 24-hour healthcare, commerce and production, and expanding social life around the clock. However, physiology and behavior that evolved in the context of 24 h solar days are frequently perturbed by exposure to artificial light at night. This is particularly salient in the context of circadian rhythms, the result of endogenous biological clocks with a rhythm of ~24 h. Circadian rhythms govern the temporal features of physiology and behavior, and are set to precisely 24 h primarily by exposure to light during the solar day, though other factors, such as the timing of meals, can also affect circadian rhythms. Circadian rhythms are significantly affected by night shift work because of exposure to nocturnal light, electronic devices, and shifts in the timing of meals. Night shift workers are at increased risk for metabolic disorder, as well as several types of cancer. Others who are exposed to artificial light at night or late mealtimes also show disrupted circadian rhythms and increased metabolic and cardiac disorders. It is imperative to understand how disrupted circadian rhythms alter metabolic function to develop strategies to mitigate their negative effects. In this review, we provide an introduction to circadian rhythms, physiological regulation of homeostasis by the suprachiasmatic nucleus (SCN), and SCN-mediated hormones that display circadian rhythms, including melatonin and glucocorticoids. Next, we discuss circadian-gated physiological processes including sleep and food intake, followed by types of disrupted circadian rhythms and how modern lighting disrupts molecular clock rhythms. Lastly, we identify how disruptions to hormones and metabolism can increase susceptibility to metabolic syndrome and risk for cardiovascular diseases, and discuss various strategies to mitigate the harmful consequences associated with disrupted circadian rhythms on human health.

Hartmann's procedure versus primary anastomosis for Hinchey stage III diverticulitis: a prospective case-control study.

INTRODUCTION: Hartmann's procedure (HP) is the conventional treatment in patients with complicated diverticulitis. Segmental resection with primary anastomosis (PA) is a treatment alternative for those patients. Our aim was to compare the postoperative results of HP and PA in patients with complicated diverticulitis (Hinchey stage III). METHODS: A case-control study was conducted on patients operated on for purulent Hinchey stage III diverticulitis, within the time frame of 2000 and 2019. RESULTS: Twenty-seven patients that underwent PA were compared with 27 that underwent HP. The patients that underwent HP had a greater probability of morbidity at 30 days (OR 3.5; 95% CI 1.13-11.25), as well as a greater probability of major complications (OR 10.9; 95% CI 1.26-95.05). CONCLUSION: The patients that underwent segmental resection and PA presented with lower morbidity rates and higher stoma reversal rates than the patients that underwent HP.

Chronic exposure to dim light at night disrupts cell-mediated immune response and decreases longevity in aged female mice.

Circadian rhythms are endogenous biological cycles that regulate physiology and behavior for optimal adaptive function and survival; they are synchronized to precisely 24 hours by daily light exposure. Disruption of the daily light-dark (LD) cycle by exposure to artificial light at night (ALAN) dysregulates core clock genes and biological function. Exposure to ALAN has been associated with increased health risks in humans, and elderly individuals are at elevated risk for poor outcome from disease and often experience elevated exposure to ALAN due to increased care requirements. The role of disrupted circadian rhythms in healthy, aged animals remains unspecified; thus, we hypothesized that disrupted circadian rhythms via chronic exposure to dim ALAN (dLAN) impair immune response and survival in aged mice. Twenty-month-old C57BL/6 male and female mice were exposed to 24 weeks of LD conditions or dLAN (5 lux); then, cell-mediated immune response was assessed using a delayed-type hypersensitivity test. Aged female mice exposed to dLAN displayed dysregulated hypersensitivity and inflammation as a measure of cell-mediated immune response and decreased lifespan compared to females housed in dark nights. Nighttime lighting did not affect cell-mediated immune response or lifespan in males but dysregulated body mass and increased adrenal mass after immune challenge after chronic exposure to dLAN. Together, these data indicate that chronic exposure to dLAN affects lifespan in aged females and suggest that females are more susceptible to the detrimental consequences of disrupted circadian rhythms.

Consensus statement on the use of alemtuzumab in daily clinical practice in Spain.

INTRODUCTION: Alemtuzumab is a highly effective drug approved by the European Medicines Agency as a disease-modifying drug for the treatment of relapsing-remitting multiple sclerosis. OBJECTIVE: A consensus document was drafted on the management of alemtuzumab in routine clinical practice in Spain. DEVELOPMENT: A group of multiple sclerosis specialists reviewed articles addressing treatment with alemtuzumab in patients with multiple sclerosis and published before December 2017. The included studies assessed the drug's efficacy, effectiveness, and safety; screening for infections and vaccination; and administration and monitoring aspects. The initial proposed recommendations were developed by a coordinating group and based on the available evidence and their clinical experience. The consensus process was carried out in 2 stages, with the initial threshold percentage for group agreement established at 80%. The final document with all the recommendations agreed by the working group was submitted for external review and the comments received were considered by the coordinating group. CONCLUSION: The present document is intended to be used as a tool for optimising the management of alemtuzumab in routine clinical practice.

Consenso de expertos sobre el uso de alemtuzumab en la práctica clínica diaria en España / Consensus statement on the use of alemtuzumab in daily clinical practice in Spain

Introducción: Alemtuzumab es un fármaco de alta eficacia aprobado por la Agencia Europea de Medicamentos como tratamiento modificador de la enfermedad en pacientes con esclerosis múltiple remitente recurrente.ObjetivoElaborar un documento de consenso sobre el manejo de alemtuzumab en la práctica clínica habitual, que sea de aplicación en el ámbito español.DesarrolloUn grupo de expertos en esclerosis múltiple revisó las publicaciones disponibles hasta diciembre de 2017, de tratamiento con alemtuzumab y esclerosis múltiple. Se incluyeron trabajos sobre eficacia, efectividad y seguridad, despistaje de infecciones y vacunación, administración y monitorización. La propuesta inicial de recomendaciones fue desarrollada por un grupo coordinador con base en la evidencia disponible y en su experiencia clínica. El proceso de consenso se llevó a cabo en 2 etapas; se estableció como porcentaje inicial de acuerdo grupal el 80%. El documento final con todas las recomendaciones acordadas por el grupo de trabajo se sometió a revisión externa y los comentarios recibidos fueron considerados por el grupo coordinador.ConclusionesEl documento aportado pretende ser una herramienta útil para facilitar el manejo del fármaco en condiciones de práctica clínica habitual. (AU)

Introduction: Alemtuzumab is a highly effective drug approved by the European Medicines Agency as a disease-modifying drug for the treatment of relapsing-remitting multiple sclerosis.ObjectiveA consensus document was drafted on the management of alemtuzumab in routine clinical practice in Spain.DevelopmentA group of multiple sclerosis specialists reviewed articles addressing treatment with alemtuzumab in patients with multiple sclerosis and published before December 2017. The included studies assessed the drug's efficacy, effectiveness, and safety; screening for infections and vaccination; and administration and monitoring aspects. The initial proposed recommendations were developed by a coordinating group and based on the available evidence and their clinical experience. The consensus process was carried out in 2 stages, with the initial threshold percentage for group agreement established at 80%. The final document with all the recommendations agreed by the working group was submitted for external review and the comments received were considered by the coordinating group.ConclusionThe present document is intended to be used as a tool for optimising the management of alemtuzumab in routine clinical practice. (AU)

Tratamiento a distancia de la insuficiencia cardiaca mediante el algoritmo HeartLogic. Registro RE-HEART / Remote heart failure management using the HeartLogic algorithm. RE-HEART registry

Introducción y objetivos HeartLogic es un algoritmo multiparamétrico incorporado a desfibriladores automáticos implantables (DAI). La alerta asociada predice descompensaciones de insuficiencia cardiaca (IC). Nuestro objetivo es analizar la asociación entre alertas y eventos clínicos bajo un protocolo de seguimiento común en un registro multicéntrico. Métodos Se evaluaron la fase 1 (investigadores ciegos al estado de la alerta) y las fases 2 y 3 (tras la activación de HeartLogic, según práctica local y un protocolo común respectivamente). Resultados Se incluyó a 288 pacientes en 15 centros. En fase 1, tras una media de observación de 10 meses, hubo 73 alertas (0,72 alertas/paciente-año), con 8 hospitalizaciones y 2 visitas a urgencias por IC (0,10 eventos/año-paciente). No hubo hospitalizaciones fuera del periodo de alerta. Las fases activas tuvieron una media de seguimiento de 16 (IC95%, 15-22) meses, con 277 alertas (0,89 alertas/año-paciente); 33 se asociaron con hospitalizaciones o muerte por IC, 46 con descompensaciones menores y 78 con otros eventos. La tasa de alertas inexplicables fue 0,39/año-paciente. Fuera del estado de alerta solo hubo una hospitalización y una descompensación menor. La mayoría de las alertas (el 82% en fase 2 y el 81% en fase 3; p=0,861) se gestionaron a distancia. La mediana de NT-proBNP fue superior en estado de alerta que fuera de él (7.378 frente a 1.210 pg/ml; p <0,001). Conclusiones El índice HeartLogic se asoció con descompensaciones de IC y otros eventos relevantes, con baja tasa de alertas inexplicables. Un protocolo estandarizado permitió detectar y actuar a distancia con seguridad sobre las alertas (AU)

Introduction and objectives HeartLogic is a multiparametric algorithm incorporated into implantable cardioverter-defibrillators (ICD). The associated alerts predict impending heart failure (HF) decompensations. Our objective was to analyze the association between alerts and clinical events and to describe the implementation of a protocol for remote management in a multicenter registry. Methods We evaluated study phase 1 (the investigators were blinded to the alert state) and phases 2 and 3 (after HeartLogic activation, managed as per local practice and with a standardized protocol, respectively). Results We included 288 patients from 15 centers. In phase 1, the median observation period was 10 months and there were 73 alerts (0.72 alerts/patient-y), with 8 hospitalizations and 2 emergency room admissions for HF (0.10 events/patient-y). There were no HF hospitalizations outside the alert period. In the active phases, the median follow-up was 16 (95%CI, 15-22) months and there were 277 alerts (0.89 alerts/patient-y); 33 were associated with HF hospitalizations or HF death (n=6), 46 with minor decompensations, and 78 with other events. The unexplained alert rate was 0.39 alerts/patient-y. Outside the alert state, there was only 1 HF hospitalization and 1 minor HF decompensation. Most alerts (82% in phase 2 and 81% in phase 3; P=.861) were remotely managed. The median NT-proBNP value was higher within than outside the alert state (7378 vs 1210 pg/mL; P <.001). Conclusions The HeartLogic index was frequently associated with HF-related events and other clinically relevant situations, with a low rate of unexplained events. A standardized protocol allowed alerts to be safely and remotely detected and appropriate action to be taken on them (AU)