[Improving the nutritional care of oncology patients - Validation of a multidisciplinary protocol in the Spanish clinical setting]. / Mejorando la atención nutricional del paciente oncológico: validación de un protocolo multidisciplinar en el entorno clínico español.

Introduction: Introduction: malnutrition is a very frequent problem in oncology patients and may have serious repercussions. Adequate nutritional management is cost-effective in terms of health and survival in this population, but it requires multidisciplinary coordination, specific training, and continuous follow-up. Objective: to validate the applicability and efficacy of a multidisciplinary nutritional support protocol in oncology patients. Methods: a multidisciplinary nutritional protocol was developed for oncology patients, with guidelines for screening and assessment of malnutrition, treatment, re-evaluation, and management of side effects, as well as guidance on supplementation and eating patterns. The protocol would be implemented in various clinical centers, collecting data through a structured questionnaire, registering variables before and after implementation. Results: the protocol and its impact were implemented and evaluated in 39 centers. An improvement in nutritional care was observed, evidenced by an earlier initiation of nutritional assessment and an increase in the number of patients receiving adequate care following the protocol implementation. Problems related to inadequate malnutrition coding in the centers, limited resources, and the need for greater interdepartmental collaboration were identified. Conclusions: the conduct of this study provides insights into how the implementation of a multidisciplinary nutritional support protocol can improve the nutritional care received by patients and informs about the main obstacles to adequate implementation.

Introducción: Introducción: la desnutrición es un problema muy frecuente en el paciente oncológico y puede tener graves repercusiones. Un manejo nutricional adecuado es coste-efectivo en términos de salud y supervivencia en esta población, pero requiere de coordinación multidisciplinar, formación específica y seguimiento continuo. Objetivo: validar la aplicabilidad y eficacia de un protocolo multidisciplinar de soporte nutricional en pacientes oncológicos. Métodos: se desarrolló un protocolo nutricional multidisciplinar para pacientes oncológicos, con pautas para el cribado y valoración de la desnutrición, el tratamiento, la reevaluación y la gestión de los efectos secundarios, además de orientaciones sobre suplementación y patrones de alimentación. Se implementaría el protocolo en diversos centros clínicos, recogiendo datos a través de un cuestionario estructurado, registrando variables antes y después de la implementación. Resultados: se implementó y se valoraron el protocolo y su impacto en 39 centros. Se observó una mejoría en la atención nutricional, evidenciada por un inicio más precoz de la valoración nutricional y un aumento en el número de pacientes que recibían atención adecuada tras la implementación del protocolo. Se identificaron problemas relacionados con una inadecuada codificación de la desnutrición en los centros, recursos limitados y la necesidad de mayor colaboración interdepartamental. Conclusiones: la realización de este estudio ofrece información de cómo la implementación de un protocolo multidisciplinar de soporte nutricional puede contribuir a mejorar la atención nutricional que reciben los pacientes e informa de cuáles son los principales obstáculos para una implementación adecuada.

The cellular basis of feeding-dependent body size plasticity in sea anemones.

Many animals share a lifelong capacity to adapt their growth rates and body sizes to changing environmental food supplies. However, the cellular and molecular basis underlying this plasticity remains only poorly understood. We therefore studied how the sea anemones Nematostella vectensis and Aiptasia (Exaiptasia pallida) respond to feeding and starvation. Combining quantifications of body size and cell numbers with mathematical modelling, we observed that growth and shrinkage rates in Nematostella are exponential, stereotypic and accompanied by dramatic changes in cell numbers. Notably, shrinkage rates, but not growth rates, are independent of body size. In the facultatively symbiotic Aiptasia, we show that growth and cell proliferation rates are dependent on the symbiotic state. On a cellular level, we found that >7% of all cells in Nematostella juveniles reversibly shift between S/G2/M and G1/G0 cell cycle phases when fed or starved, respectively. Furthermore, we demonstrate that polyp growth and cell proliferation are dependent on TOR signalling during feeding. Altogether, we provide a benchmark and resource for further investigating the nutritional regulation of body plasticity on multiple scales using the genetic toolkit available for Nematostella.

Plasma inflammation for predicting phenotypic conversion and clinical progression of autosomal dominant frontotemporal lobar degeneration.

BACKGROUND: Measuring systemic inflammatory markers may improve clinical prognosis and help identify targetable pathways for treatment in patients with autosomal dominant forms of frontotemporal lobar degeneration (FTLD). METHODS: We measured plasma concentrations of IL-6, TNFα and YKL-40 in pathogenic variant carriers (MAPT, C9orf72, GRN) and non-carrier family members enrolled in the ARTFL-LEFFTDS Longitudinal Frontotemporal Lobar Degeneration consortium. We evaluated associations between baseline plasma inflammation and rate of clinical and neuroimaging changes (linear mixed effects models with standardised (z) outcomes). We compared inflammation between asymptomatic carriers who remained clinically normal ('asymptomatic non-converters') and those who became symptomatic ('asymptomatic converters') using area under the curve analyses. Discrimination accuracy was compared with that of plasma neurofilament light chain (NfL). RESULTS: We studied 394 participants (non-carriers=143, C9orf72=117, GRN=62, MAPT=72). In MAPT, higher TNFα was associated with faster functional decline (B=0.12 (0.02, 0.22), p=0.02) and temporal lobe atrophy. In C9orf72, higher TNFα was associated with faster functional decline (B=0.09 (0.03, 0.16), p=0.006) and cognitive decline (B=-0.16 (-0.22, -0.10), p<0.001), while higher IL-6 was associated with faster functional decline (B=0.12 (0.03, 0.21), p=0.01). TNFα was higher in asymptomatic converters than non-converters (ß=0.29 (0.09, 0.48), p=0.004) and improved discriminability compared with plasma NfL alone (ΔR2=0.16, p=0.007; NfL: OR=1.4 (1.03, 1.9), p=0.03; TNFα: OR=7.7 (1.7, 31.7), p=0.007). CONCLUSIONS: Systemic proinflammatory protein measurement, particularly TNFα, may improve clinical prognosis in autosomal dominant FTLD pathogenic variant carriers who are not yet exhibiting severe impairment. Integrating TNFα with markers of neuronal dysfunction like NfL could optimise detection of impending symptom conversion in asymptomatic pathogenic variant carriers and may help personalise therapeutic approaches.

Morbimortalidad asociada a la disfagia en pacientes ingresados en un hospital general universitario

RESUMEN Introducción: La disfagia tiene una morbimortalidad importante en pacientes hospitalizados. Objetivos: principal; describir las características de los pacientes con disfagia hospitalizados y, secundarios; cuantificar y analizar la prevalencia de mortalidad y de reingresos. Metodología: Estudio transversal descriptivo de las hospitalizaciones por disfagia durante el año 2015 en un Hospital General Universitario. Resultados: Se evaluaron 431 historias clínicas. La edad de los pacientes fue de 83,21 (DE 11,4) años, el 52,5% fueron mujeres y el 47,2% varones; la estancia media fue de 11,1 (DE 7,99) días. En el 71,2 % de los casos la disfagia fue por afectación de la fase orofaríngea. En el 80,51% de los casos se diagnosticaron complicaciones respiratorias: 48,12% neumonía aspirativa por líquidos, 40,05 % neumonitis química por aspiración y 11,81% neumonía aspirativa por sólidos. La mortalidad general asociada a las complicaciones respiratorias respecto del total de los casos de disfagia fue del 24,49%. El 50,48% de los pacientes con neumonía aspirativa fallecieron. La principal causa de la disfagia fue las enfermedades neurológicas (un 77,25%). La mortalidad fue significativamente mayor en las mujeres - 42,3% frente al 7,8% - (p < 0,01) y esta diferencia se mantuvo tras ajustar el resultado por edad: OR 9,937, IC95%: 5,446; 18,131. El 13,10% de los pacientes reingresaron al menos en una ocasión. Los pacientes de geriatría presentaron un mayor número de reingresos por número de ingresos. Discusión: las enfermedades neurológicas fueron la principal causa de disfagia. La mortalidad fue significativamente mayor en las mujeres.

ABSTRACT Introduction: Dysphagia is an important associated morbidity and mortality in hospitalized patient. Objectives: Main; to describe the characteristics of patients admitted for dysphagia and secondary; quantify and analyze the prevalence of mortality and readmissions. Methodology: Cross-sectional study descriptive revenues by dysphagia during the year 2015 in a University General Hospital. Results: 431 records were evaluated. The age of the patients was 83,21 (11.4), 52.5% women and 47.2% male; the average stay was 11.1 (7.99) days. In 71,2% of cases the dysphagia was involvement of the oropharyngeal phase. 80.51% of cases were diagnosed respiratory complications. The percentage distribution of these complications were: in 48.12% aspiration pneumonia due to fluids, in 40.05% chemical aspiration pneumonitis and in 11.81% aspiration pneumonia due to solids. The overall mortality associated with respiratory complications compared to the total of cases of dysphagia was 24.49%. 50.48% of patients diagnosed with aspiration pneumonia died. The main cause of dysphagia was neurological diseases (77.25%). Mortality was significantly higher in women - 42.3% of women compared with 7.8% of males - (p < 0.01) and this difference remained after adjusting the result by age: OR 9,937, 95% CI: 5,446; 18,131. 13.10% of patients re-entered at least on one occasion. Patients of geriatric unit that presented in greater number of readmissions by admissions. Discussion: neurological diseases were the main cause of dysphagia. Mortality was significantly higher in women

Restoring regulatory T-cell dysfunction in Alzheimer's disease through ex vivo expansion.

Inflammation is a significant component of Alzheimer's disease pathology. While neuroprotective microglia are important for containment/clearance of Amyloid plaques and maintaining neuronal survival, Alzheimer inflammatory microglia may play a detrimental role by eliciting tau pathogenesis and accelerating neurotoxicity. Regulatory T cells have been shown to suppress microglia-mediated inflammation. However, the role of regulatory T cells in ameliorating the proinflammatory immune response in Alzheimer's disease requires further investigation. Forty-six patients with Alzheimer disease, 42 with mild cognitive impairment and 41 healthy controls were studied. The phenotypes of peripheral regulatory T cells were assessed with multicolour flow cytometry. Regulatory T cells were co-cultured with responder T cells and proliferation was determined by 3H-thymidine incorporation. In separate experiments, regulatory T cells were added to induced pluripotent stem cell-derived pro-inflammatory macrophages and changes in interleukin-6/tumour necrosis-alpha transcripts and protein levels were measured. Freshly isolated regulatory T cells were expanded ex vivo in the presence of CD3/CD28 expander beads, interleukin-2 and rapamycin to promote their suppressive function. We found that the suppressive function of regulatory T cells on responder T-cell proliferation was compromised at the Alzheimer disease stage, compared with mild cognitive impairment and healthy controls. CD25 mean fluorescence intensity in regulatory T-cell population was also reduced in Alzheimer dementia patients. Regulatory T cells did not suppress pro-inflammatory macrophages at baseline. Following ex vivo expansion, regulatory T-cell suppression of responder T-cell proliferation and pro-inflammatory macrophage activation increased in both patients and controls. Expanded regulatory T cells exerted their immunoregulatory function on pro-inflammatory macrophages through a contact-mediated mechanism. In conclusion, regulatory T-cell immunophenotype and function are compromised in Alzheimer's disease. Following ex vivo expansion, the immunomodulatory function of regulatory T cells is enhanced even at advanced stages of Alzheimer's disease. Restoration of regulatory T-cell function could be explored as a means to modulate the inflammatory status of Alzheimer's disease.

Head-to-head comparison of 11C-PBR28 and 11C-ER176 for quantification of the translocator protein in the human brain.

INTRODUCTION: 11C-ER176 is a new PET tracer to quantify the translocator protein (TSPO), a biomarker for inflammation. The aim of this study was to perform a head-to-head comparison between 11C-ER176 and the widely used 11C-PBR28. METHODS: Seven healthy volunteers had a 90-min PET scan and metabolite-corrected arterial input function with 11C-PBR28 in the morning and 11C-ER176 in the afternoon. Binding was quantified at the regional level in terms of VT with a two-tissue compartmental model. By using VND values from the literature obtained with pharmacological blockade, we derived the binding potential BPND for both tracers. RESULTS: 11C-ER176 was more stable in arterial blood than 11C-PBR28 (the percentages of unmetabolized parent in plasma at 90 min were 29.0 ± 8.3% and 8.8 ± 2.9% respectively). The brain time-activity curves for both tracers were well fitted by the two-tissue model, but 11C-ER176 had higher VT values than 11C-PBR28 (5.74 ± 1.54 vs 4.43 ± 1.99 ml/cm3) and a lower coefficient of variation. The BPND of 11C-ER176 was more than 4 times larger than that of 11C-PBR28 for high-affinity binders, and more than 9 times larger for mixed-affinity binders. CONCLUSION: 11C-ER176 displays a higher binding potential and a smaller variability of VT values. Thanks to these characteristics, clinical studies performed with 11C-ER176 are expected to have higher statistical power and thus require fewer subjects.

Hypothalamic relapse of a cardiac large B-cell lymphoma presenting with memory loss, confabulation, alexia-agraphia, apathy, hypersomnia, appetite disturbances and diabetes insipidus.

A 37-year-old Hispanic man with a right atrial intracardiac mass diagnosed as diffuse large B-cell lymphoma (DLBCL) was successfully treated with surgery and chemotherapy. During 4 years, several total-body positron emission tomography and MRI scans showed no extracardiac lymphoma. On year 5 after the cardiac surgery, patient presented with sleepiness, hyperphagia, memory loss, confabulation, dementia and diabetes insipidus. Brain MRI showed a single hypothalamic recurrence of the original lymphoma that responded to high-dose methotrexate treatment. Correction of diabetes insipidus improved alertness but amnesia and cognitive deficits persisted, including incapacity to read and write. This case illustrates two unusual locations of DLBCL: primary cardiac lymphoma and hypothalamus. We emphasise the importance of third ventricle tumours as causing amnesia, confabulation, behavioural changes, alexia-agraphia, endocrine disorders and alterations of the circadian rhythm of wakefulness-sleep secondary to lesions of specific hypothalamic nuclei and disruption of hypothalamic-thalamic circuits.

New mutation in female patient with renal variant of Fabry disease and HIV.

We describe the case of a 27-year-old woman with a family history of Anderson-Fabry disease (AFD). Urinary sediment presented microhematuria and 0.9 g/24 hours proteinuria. The alpha-galactosidase A measurement in fibroblasts showed partial deficit of the enzyme, which was compatible with being a carrier of the illness. Renal biopsy gave evidence of kidney lesions from Fabry disease. Genetic study revealed mutation C52Y or Cys52Tyr, which has not been previously described and had also been detected in the father of the patient. During follow-up, the presence of hypergammaglobulinemia revealed an underlying HIV disease. She is now awaiting enzymatic substitution treatment.

Ventricular wall granulations and draining of cerebrospinal fluid in chronic giant hydrocephalus.

BACKGROUND: In rare cases, adults with normal or almost normal cognition may have giant brain ventricles surrounded by a sliver of brain. Because the usual flow of cerebrospinal fluid (CSF) is interrupted in these individuals, they may develop alternative CSF pathways to preserve brain function. OBJECTIVE: To describe novel morphologic autopsy findings in a patient with chronic giant hydrocephalus that suggest the existence of alternative CSF draining pathways. DESIGN: Case report. SETTING: Autopsy study. PATIENT: A 48-year-old man with chronic compensated hydrocephalus associated with a Dandy-Walker malformation. MAIN OUTCOME MEASURE: Autopsy findings. RESULTS: We observed microscopic structures on the ventricular wall that may facilitate CSF resorption. Their histologic appearance, reminiscent of pacchionian granulations, showed the opposite relation in regard to CSF/blood compartments: whereas the core of a pacchionian granulation contains CSF and the granulation is bathed in blood of the venous sinus, the core of the ventricular granulation in our patient contained venules, with the granulation bathed in ventricular CSF. CONCLUSIONS: These previously unreported (to our knowledge) ventricular wall granulations may facilitate draining of CSF into the venous system when CSF outflow from the ventricular system is occluded. The presence of these ventricular structures illustrates biologic adaptation to anomalous conditions and successful compensation.