Recommendations for the diagnosis and treatment of Clostridioides difficile infection: An official clinical practice guideline of the Spanish Society of Chemotherapy (SEQ), Spanish Society of Internal Medicine (SEMI) and the working group of Postoperative Infection of the Spanish Society of Anesthesia and Reanimation (SEDAR) / Recomendaciones para el diagnóstico y tratamiento de la infección por Clostridioides difficile. Guía de práctica clínica de la Sociedad Española de Quimioterapia, Sociedad Española de Medicina Interna y grupo de trabajo de Infección Postoperatoria de la Sociedad Española de Anestesia y Reanimación

This document gathers the opinion of a multidisciplinary forum of experts on different aspects of the diagnosis and treatment of Clostridioides difficile infection (CDI) in Spain. It has been structured around a series of questions that the attendees considered relevant and in which a consensus opinion was reached. The main messages were as follows: CDI should be suspected in patients older than 2 years of age in the presence of diarrhea, paralytic ileus and unexplained leukocytosis, even in the absence of classical risk factors. With a few exceptions, a single stool sample is sufficient for diagnosis, which can be sent to the laboratory with or without transportation media for enteropathogenic bacteria. In the absence of diarrhoea, rectal swabs may be valid. The microbiology laboratory should include C. difficile among the pathogens routinely searched in patients with diarrhoea. Laboratory tests in different order and sequence schemes include GDH detection, presence of toxins, molecular tests and toxigenic culture. Immediate determination of sensitivity to drugs such as vancomycin, metronidazole or fidaxomycin is not required. The evolution of toxin persistence is not a suitable test for follow up. Laboratory diagnosis of CDI should be rapid and results reported and interpreted to clinicians immediately. In addition to the basic support of all diarrheic episodes, CDI treatment requires the suppression of antiperistaltic agents, proton pump inhibitors and antibiotics, where possible. Oral vancomycin and fidaxomycin are the antibacterials of choice in treatment, intravenous metronidazole being restricted for patients in whom the presence of the above drugs in the intestinal lumen cannot be assured. Fecal material transplantation is the treatment of choice for patients with multiple recurrences but uncertainties persist regarding its standardization and safety. Bezlotoxumab is a monoclonal antibody to C. difficile toxin B that should be administered to patients at high risk of recurrence. Surgery is becoming less and less necessary and prevention with vaccines is under research. Probiotics have so far not been shown to be therapeutically or preventively effective. The therapeutic strategy should be based, rather than on the number of episodes, on the severity of the episodes and on their potential to recur. Some data point to the efficacy of oral vancomycin prophylaxis in patients who reccur CDI when systemic antibiotics are required again

El presente documento recoge la opinión de un foro multidisciplinar de expertos sobre distintos aspectos del diangóstico y tratamiento de la infección por Clostridioides difficile (CDI) en España. Se ha estructurado alrededor de una serie de preguntas que los asistentes consideraron pertinentes y en las que se llegó a una opinión de consenso. Los principales mensajes fueron los siguientes: CDI debe sospecharse en pacientes mayores de 2 años de edad ante la presencia de diarrea, ileo paralítico y leucocitosis inexplicada, aún en ausencia de los factores de riesgo clásicos. Salvo excepciones, es suficiente con una sola muestra de heces para su diagnóstico que pueden ser enviadas al laboratorio con o sin medio de transporte para bacterias enteropatógenas. En ausencia de diarrea, pueden ser válidos los isopados rectales. El laboratorio de microbiología debe incluir a C. difficile entre los patógenos buscados de rutina en pacientes con diarrea. Las pruebas de laboratorio en diferentes esquemas de orden y secuencia incluyen la detección de GDH, la presencia de toxinas, las pruebas moleculares y el cultivo toxigénico. No se precisa la determinación inmediata de sensibilidad frente a fármacos como vancomicina, metronidazol o fidaxomicina. La evolución de la persistencia de toxina no es un test adecuado para el seguimiento del proceso. Además del soporte básico de toda diarrea, el tratamiento de CDI requiere la supresión de los agentes antiperistálticos, de los inhibidores de la bomba de protones y de los antibióticos, cuando sea posible. Vancomicina oral y fidaxomicina son los antibacterianos de elección en el tratamiento, restringiéndose metronidazol intravenoso para enfermos en los que no se pueda asegurar la presencia en la luz intestinal de los fármacos anteriores. El trasplante de materia fecal es el tratamiento de elección para pacientes con múltiples recurrencias pero persisten incertidumbres sobre su estandarización y seguridad. Bezlotoxumab es un anticuerpo monoclonal frente a la toxina B de C. difficile que debe administrarse a pacientes con alto riesgo de recurrencias. La cirugía es un procedimiento cada vez menos necesario y la prevención mediante vacunas se encuentra en fase de investigación. Los probióticos no han demostrado, hasta el momento, eficacia terapéutica ni preventiva. La estrategia terapéutica debe basarse, más que en el número de episodios, en la gravedad de los mismos y en la potencialidad de recurrir. Algunos datos apuntan a la eficacia de la profilaxis con vancomicina oral en pacientes que recurren cuando vuelven a precisar antibióticos sistémicos

Immune Function, Oxidative, and Inflammatory Markers in Centenarians as Potential Predictors of Survival and Indicators of Recovery After Hospital Admission.

Several parameters of immune function, oxidative, and inflammatory stresses have been proposed as markers of health and predictors of longevity and mortality. However, it is unknown if any of these parameters can be used as predictors of survival in centenarians. Therefore, in a group of 27 centenarians, at the time of admission to the Clinical Hospital of Madrid, a series of immune function, antioxidant, oxidant, and inflammatory parameters were studied. Some centenarians survived and others did not, thus establishing two groups, "survivors" (n = 9) and "nonsurvivors" (n = 18). The results show that surviving centenarians display higher neutrophil chemotaxis and microbicidal capacity, natural killer activity, lymphoproliferation, glutathione reductase activity, and basal interleukin-10 release. Moreover, lower neutrophil and lymphocyte adherence, superoxide anion and malondialdehyde concentrations, and basal release of tumor necrosis factor α are also reported. The odds ratios for survival for these parameters were also calculated, with the highest odds ratios being the lymphoproliferative capacity and the ex vivo basal and stimulated release of interleukin-6 from mononuclear cells (odds ratio = 136.00). Therefore, these parameters have the potential to be used in the clinical setting as predictors of survival in centenarians. In the survivors group, the same parameters were also analyzed after 3 months. Because survivors showed an increase in neutrophil and lymphocyte chemotaxis capacity during the recovery period, reaching similar values to those observed in healthy centenarians, these parameters could be proposed as indicators of recovery.

Intervención geriátrica en el anciano ingresado por fractura de cadera en el Hospital Universitario de Guadalajara: repercusión clínica, asistencial y económica / Geriatric intervention in elderly hip fracture patients admitted to University Hospital of Guadalajara: clincal, healthcare and economical repercussions

Objetivo. Evaluar los resultados asistenciales y la repercusión económica de la intervención geriátrica en pacientes mayores de 75 años con fractura de cadera en fase aguda. Material y métodos. Estudio retrospectivo de los pacientes ingresados por fractura de cadera en el Hospital Universitario de Guadalajara (HUGU). Se evaluaron parámetros asistenciales del total de los pacientes ingresados por fractura de cadera en el HUGU entre los años 2002 y 2013 (n=2.942), tales como número anual de casos, la estancia preoperatoria, la estancia global y la mortalidad. Evaluación del efecto de la intervención geriátrica protocolizada iniciada en 2006 mediante la comparación de datos entre las etapas previa y posterior a su puesta en marcha. Resultados. La intervención geriátrica ha supuesto una reducción progresiva de estancia media y la mortalidad, aunque con una tendencia aumentar la estancia prequirúrgica. Comparando la actividad del 2013 con la del 2006, la estancia media se redujo del 18,5 al 11,2 días (-39,2%) y la mortalidad desde el 8,9 hasta el 6,8% (-23%). Por el contrario, la estancia preoperatoria media se mantuvo en 2,7 días de media en los años postintervención, frente a 2,4 en los años previos. A pesar del incremento anual del precio diario de la hospitalización por factura de cadera, el descenso de la estancia implica una reducción del coste del proceso que supera los 900.000 euros anuales. Conclusiones. La intervención geriátrica contribuye a la reducción observada de la mortalidad y la estancia hospitalaria por fractura de cadera, disminuyendo el coste de la hospitalización (AU)

Objective. To evaluate the healthcare outcomes and economic impact of geriatric intervention in patients over 75 years old with hip fracture in acute phase. Material and methods. Retrospective study of patients admitted to the University Hospital of Guadalajara (HUGU) due to hip fracture. An analysis was made of the number of cases per year, preoperative period, hospital stay, and mortality of all the patients over 75 years admitted to the HUGU due to hip fracture between 2002 and 2013. Results. A total of 2942 patients were included. Comparing the activity of 2013 to that of 2006, the mean hospital stay fell from 18.5 to 11.2 days (-39.2%), and mortality from 8.9% to 6.8% (-23%). In contrast, the mean preoperative stay remained at a mean of 2.7 days versus 2.4 in previous years in the early post-intervention period. Hospital stay decreased, despite a progressive annual increase in the daily cost of hospitalisation due to hip fracture surgery, the reduced stay led to a reduction of the total cost by more than 900,000 euros each year. Geriatric intervention has gradually reduced mean hospital stay and mortality, although with a tendency to increase mean preoperative stay. Conclusions. Geriatric intervention in patients with hip fracture reduces mortality and length of hospital stay, and decreasing costs (AU)

[Geriatric intervention in elderly hip fracture patients admitted to University Hospital of Guadalajara: Clincal, healthcare and economical repercussions]. / Intervención geriátrica en el anciano ingresado por fractura de cadera en el Hospital Universitario de Guadalajara: repercusión clínica, asistencial y económica.

OBJECTIVE: To evaluate the healthcare outcomes and economic impact of geriatric intervention in patients over 75 years old with hip fracture in acute phase. MATERIAL AND METHODS: Retrospective study of patients admitted to the University Hospital of Guadalajara (HUGU) due to hip fracture. An analysis was made of the number of cases per year, preoperative period, hospital stay, and mortality of all the patients over 75 years admitted to the HUGU due to hip fracture between 2002 and 2013. RESULTS: A total of 2942 patients were included. Comparing the activity of 2013 to that of 2006, the mean hospital stay fell from 18.5 to 11.2 days (-39.2%), and mortality from 8.9% to 6.8% (-23%). In contrast, the mean preoperative stay remained at a mean of 2.7 days versus 2.4 in previous years in the early post-intervention period. Hospital stay decreased, despite a progressive annual increase in the daily cost of hospitalisation due to hip fracture surgery, the reduced stay led to a reduction of the total cost by more than 900,000 euros each year. Geriatric intervention has gradually reduced mean hospital stay and mortality, although with a tendency to increase mean preoperative stay. CONCLUSIONS: Geriatric intervention in patients with hip fracture reduces mortality and length of hospital stay, and decreasing costs.

Delayed surgery in hip fracture patients. Can we afford it?

The aim is to analyze whether time to surgery (TtoS) in hip fracture patients is associated with longer than expected length of stay (LofS) and whether there is any particular group in which this is especially relevant. We developed an observational study in Madrid, Spain. From 771 patients admitted to the orthopedic ward, we selected 723 with surgical delay ≤7 days. Age was characterized as younger (<81), elderly (81-90), very elderly (>90). Modified Barthel Index was classified as very dependent (<41), moderately dependent (41-80), independent (>80). RESULTS: Median (IQR) TtoS was 3 (1-4) days; LofS 12 (7-15). Mean age was 84.3 years, 78.4% were women. TtoS was associated with LofS, which increased by 1.80 days (95% CI, 1.50-2.10) per delayed day (p<0.001). After adjustment for age, sex, functional status, we found an increase of 1.75 days (1.46-2.04) per day (p<0.001). We did not find effect of age or sex. Functional status had a higher effect in moderately dependent patients 2.25 days (1.78-2.72) than in very dependent or independent patients, 1.33 (0.37-2.30) and 1.50 days (1.09-1.91) respectively (p 0.012). As conclusion we could affirm that increasing TtoS leads to longer than expected LofS in hip fracture patients, particularly moderately dependent patients. Copyright © 2016 John Wiley & Sons, Ltd.

Síndrome coronario agudo en una nonagenaria, de la clínica a la evidencia / Acute coronary syndrome in a nonagenarian; from the clinic to the evidence

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Role of the immune system in aging and longevity.

The aging process is a universal, intrinsic, progressive accumulation of deleterious changes in cells and tissues that increases morbidity and leads to death. The heterogeneity of the age-related physiological changes is shown by the "biological age", which determines the rate of ageing experienced by each individual and therefore his life expectancy. According to the recent theory of oxidation-inflammation to explain the aging process, the immune system seems to be involved in the chronic oxidative and inflammatory stress conditions of aging. It has been proposed that several age-related changes in immune cell functions, which depend on the redox state of these cells, could be good markers of health, biological age and longevity. In order to identify parameters of the functional and redox situation of immune cells as markers of biological age and predictors of longevity, we have studied those parameters in human healthy centenarians, in extreme long-living mice, as models of successful aging, and in immune cells from murine models of premature immunosenescence. The aim of the present work is to review the results in humans and rodents on those parameters and their relationship with biological age and longevity, as well as to propose several strategies of lifestyle useful to improve the immune function and thus to increase the mean life span.

Neutrophils of centenarians show function levels similar to those of young adults.

OBJECTIVES: To analyze several functions and antioxidant parameters of peripheral blood neutrophils from healthy centenarians (men and women) and compare them with those of healthy young (aged 25-35) and middle-aged (aged 65-75) men and women. DESIGN: Cross-sectional study. SETTING: Community-based. PARTICIPANTS: Twenty-one healthy centenarians (8 men), 30 young adults (15 men), and 30 middle-aged adults (15 men). MEASUREMENTS: Several neutrophil functions (adherence, chemotaxis, phagocytosis, and stimulated and nonstimulated intracellular superoxide anion levels) and antioxidant parameters (glutathione levels and catalase activity) were measured in peripheral blood neutrophil suspension in the three study groups. RESULTS: Neutrophil functions of the middle-aged group were worse than those of young adults and centenarians (lower chemotaxis and phagocytosis and higher adherence and superoxide anion levels). The neutrophil functions of the centenarians were closer to those of the young adults. Age-related differences in neutrophil functions were fundamentally similar in men and women, except for intracellular superoxide anion levels, which were lower in young adult women than in young adult men. With normal aging, total glutathione levels decrease, but the centenarians in this study showed levels similar to those of young adults. Centenarians showed the highest catalase activity of the three groups. CONCLUSION: Progressive impairment of the immune system accompanies aging. The better preservation of function and antioxidant systems in the neutrophils of centenarians could play a key role in the longevity of these subjects.

[Immunological markers of ageing]. / Marcadores inmunológicos de envejecimiento.

Ageing is a process involving morphological and physiological modifications that gradually appear with time and lead to death. Given the heterogeneous nature of the process among individuals and among the different organs, tissues, and systems in the same individual, the concept of <> has been developed. The search for parameters that enable us to evaluate biological age--and therefore longevity--and the analysis of the efficacy of strategies to retard the ageing process are the objectives of gerontology. At present, one of the most important theories of ageing is the <> theory. Given that immune cell function is an excellent marker of health, we review the concepts that enable different functional and oxidative stress parameters in immune cells to be identified as markers of biological age and longevity. None of these parameters is universally accepted as a biomarker of ageing, although they are becoming increasingly important.

Marcadores inmunológicos de envejecimiento / Immunological markers of ageing

El envejecimiento es un proceso de modificaciones morfológicasy fisiológicas, que aparecen progresivamente por la acción deltiempo y llevan a la muerte. Debido a la heterogeneidad del procesoentre distintos individuos, e incluso entre diferentes tejidos,órganos y sistemas del mismo individuo, se ha desarrollado elconcepto de «edad biológica». La búsqueda de parámetros capacesde valorar la edad biológica del individuo y, consecuentemente,su longevidad, así como analizar la eficacia de estrategiasde actuación que permitan hacer más lento el proceso de envejecimiento,son objetivos de la gerontología. Una de las teoríasde envejecimiento de mayor impacto actualmente es la «oxidativainflamatoria». Dado que la funcionalidad de las células inmunológicases un excelente marcador de la salud, se revisarán los conceptosque están permitiendo establecer diferentes parámetrosfuncionales y de estrés oxidativo en las células inmunológicascomo marcadores de edad biológica y longevidad. Ninguno deestos parámetros está universalmente aceptado como biomarcadorde envejecimiento, aunque cada vez están cobrando mayorrelevancia(AU)

Ageing is a process involving morphological and physiologicalmodifications that gradually appear with time and lead to death.Given the heterogeneous nature of the process among individualsand among the different organs, tissues, and systems in thesame individual, the concept of «biological age» has been developed.The search for parameters that enable us to evaluate biologicalage—and therefore longevity—and the analysis of the efficacyof strategies to retard the ageing process are the objectivesof gerontology. At present, one of the most important theoriesof ageing is the «oxidative-inflammatory» theory. Given that immunecell function is an excellent marker of health, we review theconcepts that enable different functional and oxidative stress parametersin immune cells to be identified as markers of biologicalage and longevity. None of these parameters is universally acceptedas a biomarker of ageing, although they are becoming increasinglyimportant(AU)