Presence of Epstein-Barr virus (EBV) antigens detected by sensitive methods has no influence on local immune environment in diffuse large B cell lymphoma.

EBV+ diffuse large B cell lymphoma (DLBCL) not otherwise specified (NOS) is a new entity confirmed by the World Health Organization (WHO) in 2017. In this new entity, the virus may contribute to a tolerogenic microenvironment. Traces of the virus have been described in DLBCL with more sensitive methods, in cases that were originally diagnosed as negative. The aim of this study was to analyze the expression of immune response genes in the tumor microenvironment to disclose the role of the virus and its traces in DLBCL. In 48 DLBCL cases, the expression of immune response genes and the presence of molecules that induce tolerance, such as TIM3, LAG3 and PDL1 by immunohistochemistry (IHC), were studied. To broaden the study of the microenvironment, tumor-associated macrophages (TMAs) were also explored. No significant differences were observed in the expression of immune response genes in the EBV+ DLBCL and those cases that were EBV- DLBCL but that exhibited viral traces, assessed by ViewRNA assay. Only the EBV+ DLBCL cases displayed a significantly higher increase in the expression of CD8 and cytotoxic T cells detected by gene expression analysis, and of PDL1 in tumor cells and in the expression of CD68 in the tumor microenvironment detected by IHC, not observed in those cases with viral traces. The increase in CD8 and cytotoxic T cells, PDL1 and CD68 markers only in EBV+ DLBCL may indicate that traces of viral infection might not have influence in immune response markers.

Key Messages for a Frailty Prevention and Management Policy in Europe from the ADVANTAGE JOINT ACTION Consortium.

In the 2015 Ageing Report, the European Commission (EC) and the Economic Policy Committee stated that coping with the challenge posed by an ageing population will require determined policy action in Europe, particularly in reforming pension, health care and long-term care systems. The concern for this situation motivated the EC, the Parliament and many of the Member States (MS) to co-fund, in the 2015 call of the Third European Health Programme of the European Union 2014-2020, the first Joint Action (JA) on the prevention of frailty. ADVANTAGE JA brings together 33 partners from 22 MSs for 3 years. It aims to build a common understanding on frailty to be used in the MSs by policy makers and other stakeholders involved in the management, both at individual and population level, of older people who are frail or at risk for developing frailty throughout the European Union (EU). It is a formidable challenge but also a great opportunity for concerted action resulting in fostering effective and successful policies in frailty prevention and management in the participating MS. The Consortium has 2 years of hard work ahead to contribute to the needed change for frailty related disability free Europe. The first practical step towards this aim was the preparation of a document: the State of the Art on Frailty Report to support an overview of evidence of what works and what does not work on frailty prevention and management. Subsequently, this will be reflected in the advice that the JA will give to policy makers at MS level. Overall, these messages intend to be an instrument of added value to advocate for policy driven decisions on frailty prevention and management in the JA participating MSs and subsequently towards a frailty related disability free older population in Europe. The aim of this paper is to describe ADVANTAGE JA general structure, approach and recommendations towards a European health and social policy which will support frailty prevention in the participating MS.

Micosis fungoide. Experiencia en un hospital pediátrico / Mycosis Fungoides: Experience in a Pediatric Hospital

La micosis fungoide (MF) es el linfoma cutáneo primario de células T más frecuente. Su aparición en la infancia es excepcional. Objetivos: Describir las características epidemiológicas, clínicas, histopatológicas e inmunofenotípicas de los pacientes con MF. Describir los tratamientos utilizados y la evolución. Material y método: Se incluyeron todos los pacientes admitidos en el Hospital de Pediatría Dr. J. P. Garrahan (Argentina) en el período comprendido entre agosto de 1988 y julio de 2014 con diagnóstico clínico e histopatológico de MF. Resultados: Se diagnosticaron 14 pacientes con MF. La distribución por sexo fue M/F: 1:1,33. La edad media al diagnóstico fue de 11,23 años (rango: 8 a 15 años). El tiempo promedio de evolución hasta el momento del diagnóstico fue de 3 años y 6 meses (rango: 4 meses a 7 años). Todos los pacientes presentaron la forma clínica hipopigmentada y en el 42% se asoció la forma clásica. El 50% (n = 7) exhibió un inmunofenotipo CD8 positivo de forma exclusiva. El 78% presentó estadio IB. La fototerapia fue el tratamiento de elección. Cuatro pacientes tuvieron por lo menos una recaída y 3 demostraron progresión de su enfermedad a nivel cutáneo. La evolución fue favorable en todos los casos. Conclusiones: La MF es una entidad infrecuente en la infancia, siendo la forma hipopigmentada la más frecuente. Su diagnóstico es tardío debido a la similitud con otras enfermedades hipopigmentadas frecuentes en la niñez. A pesar de tener un buen pronóstico, presenta alta tasa de recidivas y requiere un seguimiento a largo plazo (AU)

Mycosis fungoides (MF), the most common primary cutaneous T-cell lymphoma, is unusual in children. Objectives: We aimed to describe the epidemiologic, clinical, histopathologic, and immunophenotypic characteristics of MF as well as treatments and course of disease in a pediatric case series. Material and method: Data for all patients admitted to our pediatric hospital (Hospital Dr. J. P. Garrahan) in Argentina with a clinical and histopathologic diagnosis of MF between August 1988 and July 2014 were included. Results: A total of 14 patients were diagnosed with MF. The ratio of boys to girls was 1:1.33. The mean age at diagnosis was 11.23 years (range, 8-15 years). The mean time between onset and diagnosis was 3.5 years (range, 4 months-7 years). All patients had hypopigmented MF and 42% also presented the features of classic MF. Seven (50%) had the CD8+ immunophenotype exclusively. Seventy-eight percent were in stage IB at presentation. Phototherapy was the treatment of choice. Four patients relapsed at least once and skin lesions progressed in 3 patients. All patients improved. Conclusions: MF is unusual in children. The hypopigmented form is the most common. Diagnosis is delayed because the condition is similar to other hypopigmented diseases seen more often in childhood. Although prognosis is good, the rate of recurrence is high, so long-term follow-up is necessary (AU)

The history of tuberculosis: from the first historical records to the isolation of Koch's bacillus.

Tuberculosis (TB) is a contagious, infectious disease, due to Mycobacterium tuberculosis (MT) that has always been a permanent challenge over the course of human history, because of its severe social implications. It has been hypothesized that the genus Mycobacterium originated more than 150 million years ago. In the Middle Ages, scrofula, a disease affecting cervical lymph nodes, was described as a new clinical form of TB. The illness was known in England and France as "king's evil", and it was widely believed that persons affected could heal after a royal touch. In 1720, for the first time, the infectious origin of TB was conjectured by the English physician Benjamin Marten, while the first successful remedy against TB was the introduction of the sanatorium cure. The famous scientist Robert Koch was able to isolate the tubercle bacillus and presented this extraordinary result to the society of Physiology in Berlin on 24 March 1882. In the decades following this discovery, the Pirquet and Mantoux tuberculin skin tests, Albert Calmette and Camille Guérin BCG vaccine, Selman Waksman streptomycin and other anti-tuberculous drugs were developed.

Mycosis Fungoides: Experience in a Pediatric Hospital. / Micosis fungoide. Experiencia en un hospital pediátrico.

Mycosis fungoides (MF), the most common primary cutaneous T-cell lymphoma, is unusual in children. OBJECTIVES: We aimed to describe the epidemiologic, clinical, histopathologic, and immunophenotypic characteristics of MF as well as treatments and course of disease in a pediatric case series. MATERIAL AND METHOD: Data for all patients admitted to our pediatric hospital (Hospital Dr. J. P. Garrahan) in Argentina with a clinical and histopathologic diagnosis of MF between August 1988 and July 2014 were included. RESULTS: A total of 14 patients were diagnosed with MF. The ratio of boys to girls was 1:1.33. The mean age at diagnosis was 11.23 years (range, 8-15 years). The mean time between onset and diagnosis was 3.5 years (range, 4 months-7 years). All patients had hypopigmented MF and 42% also presented the features of classic MF. Seven (50%) had the CD8+ immunophenotype exclusively. Seventy-eight percent were in stage IB at presentation. Phototherapy was the treatment of choice. Four patients relapsed at least once and skin lesions progressed in 3 patients. All patients improved. CONCLUSIONS: MF is unusual in children. The hypopigmented form is the most common. Diagnosis is delayed because the condition is similar to other hypopigmented diseases seen more often in childhood. Although prognosis is good, the rate of recurrence is high, so long-term follow-up is necessary.

Immune response to racotumomab in a child with relapsed neuroblastoma.

Immunotherapy targeting ganglioside antigens is a powerful tool for the treatment of high risk neuroblastoma. However, only treatment with anti-GD2 antibodies has been used in clinical practice and other options may be pursued. We report the use of racotumomab, an anti-idiotype vaccine against N-glycolyl neuraminic acid (NeuGc)- containing gangliosides, eliciting an immune response in a child with relapsed neuroblastoma expressing the NeuGcGM3 ganglioside.

Changes in severity of depressive symptoms and mortality: the Italian Longitudinal Study on Aging.

BACKGROUND: Depression is recognized as being associated with increased mortality. However, there has been little previous research on the impact of longitudinal changes in late-life depressive symptoms on mortality, and of their remission in particular. METHOD: As part of a prospective, population-based study on a random sample of 5632 subjects aged 65-84 years, with a 10-year follow-up of vital status, depressive symptoms were assessed by the 30-item Italian version of the Geriatric Depression Scale (GDS). The number of participants in the GDS measurements was 3214 at baseline and 2070 at the second survey, 3 years later. Longitudinal changes in depressive symptoms (stable, remitted, worsened) were examined in participants in both evaluations (n=1941). Mortality hazard ratios (MHRs) according to severity of symptoms and their changes over time were obtained by means of Cox proportional hazards regression models, adjusting for age and other potentially confounding factors. RESULTS: Severity is significantly associated with excess mortality in both genders. Compared to the stability of depressive symptoms, a worsened condition shows a higher 7-year mortality risk [MHR 1.46, 95% confidence interval (CI) 1.15-1.84], whereas remission reduces by about 40% the risk of mortality in both genders (women MHR 0.55, 95% CI 0.32-0.95; men MHR 0.59, 95% CI 0.37-0.93). Neither sociodemographic nor medical confounders significantly modified these associations. CONCLUSIONS: Consistent with previous reports, the severity and persistence of depression are associated with higher mortality risks. Our findings extend the magnitude of the association demonstrating that remission of symptoms is related to a significant reduction in mortality, highlighting the need to enhance case-finding and successful treatment of late-life depression.

Health care for older people in Italy: The U.L.I.S.S.E. Project (Un link informatico sui servizi sanitari esistenti per l'anziano - a computerized network on health care services for older people).

OBJECTIVES: The U.L.I.S.S.E. study is aimed at describing older patients who are cared for in hospitals, home care or nursing homes in Italy. DESIGN: The U.L.I.S.S.E. study is an observational multicenter prospective 1-year study. SETTING: Overall, 23 acute geriatric or internal medicine hospital units, 11 home care services and 31 nursing homes participated in the study. MEASUREMENTS: The patient's evaluation was performed using comprehensive geriatric assessment instruments, i.e. the interRAI Minimum Data Set, while data on service characteristics were recorded using ad-hoc designed questionnaires. RESULTS: The older subjects who are in need of acute and long term care in Italy have similar characteristics: their mean age is higher than 80 years, they have a high level of disability in ADL, an important multimorbidity, and are treated with several drugs. The prevalence of cognitive impairment is particularly high in nursing homes, where almost 70% of residents suffer from it and 40% have severe cognitive impairment. On the other hand, there is a shortage of health care services, which are heterogeneous and fragmented. CONCLUSIONS: Health care services for older people in Italy are currently inadequate to manage the complexity of the older patients. An important effort should be undertaken to create a more integrated health care system.

Alcohol consumption and metabolic syndrome in the elderly: results from the Italian longitudinal study on aging.

BACKGROUND/OBJECTIVES: Although there is plenty of evidence of the association between metabolic syndrome (MS) and cardiovascular disease, the relationship between alcohol consumption and MS is still questioned. The few publications with respect to the elderly seem to indicate that alcohol consumption is unassociated with MS. The aim of this study was to assess the association between alcohol consumption and the prevalence and incidence of MS, as well as its components in a large sample of Italian elderly people. SUBJECTS/METHODS: This is a multicenter study on a population-based sample of Italian people aged 65-84 years. The Italian Longitudinal Study on Aging (ILSA) included a prevalence phase in 1992 and an incidence phase from 1995 to 1996. The median length of follow-up was 3.5 years. In the present study, the analysis included 1321 men grouped into five alcohol consumption classes: abstainers, and those consuming or=48 g of alcohol in a day. Among the 1122 women considered, the last two of the above five categories were pooled together (>24 g/day). MS was defined according to ATP III criteria. All statistical analyses were stratified by gender. RESULTS: Adjusted odds ratios showed that categorized alcohol consumption was not significantly associated with the prevalence and incidence of MS when compared with abstainers in either gender. For the MS incidence survey, three of five components (systolic pressure, glycemia and waist circumference) proved to be significantly and harmfully affected by alcohol consumption in males, whereas no such significant association emerged in females. CONCLUSIONS: These results suggest that alcohol can modify an individual's metabolic condition and that, even among the elderly, men might be more sensitive to the effects of alcohol than women.

Apoptosis en trasplante de pulmón. Influencia del lavado y la reperfusión del órgano / Apoptosis in lung transplantation. Influence of lavage and reperfusion on the organ

Objetivo: Determinar el rol de la irrigación con soluciones de preservación, la reperfusión y el rechazo en la apoptosis pulmonar en un escenario de trasplante pulmonar. Material y método: Venticuatro cerdos Landrace con un peso de 15 a 30 kilogramos fueron usados como donantes y receptores en un modelo de trasplante pulmonar izquierdo, con 5 días de sobrevida. Las muestras se obtuvieron en la siguiente secuencia: 1A: Donante, pulmón izquierdo inmediatamente luego de la apertura del torax. 1B: donante, pulmón derecho, inmediatamente luego de la apertura del tórax. 2A: Donante pulmón izquierdo, inmediatamente luego de la irrigación del organo. 2B Donante, pulmón derecho, sin irrigar. 3A: Pulmón izquierdo implantado, 1 hora luego de reperfundido en el receptor . 3B: Pulmón derecho (nativo), 1 hora luego de reperfundido el pulmón donante en el receptor. 4A: Pulmón izquierdo, biopsia transbronquial a las 48 horas postrasplante. 4B: Pulmón derecho, biopsia transbronquial a las 48 horas postransplante. 5A: Púlmón izquierdo, 5º día postrasplante (sacrificio). Todos los pulmones fueron irrigados con solución de Euro-Collins fría (4Cº) durante la ablación. Seis receptores no recibieron inmunosupresión y otros 6 receptores recibieron 15 mg/KG/ día de ciclosporina intravenosa. Los niveles plasmáticos de ciclosporina fueron dosados en tiempo 0 al 2º y 5º día postrasplante. Cada muestra fue analizada por un observador ciego para determinar el grado de rechazo (A0 y A1 negativo. A2. A3 y A4 positivo), proliferación celular, y el índice de apaptosis en neumonocitos I y II empleando la técnica de TUNEL y Caspasa. Las pruebas de Chi cuadrado; prueba de t de student y kruskal Wallis fueron utilizadas para el análisis estadístico. Se consideró significativo un valor de p menor a 0.05. Resultados: El grado de rechazo fue negativo en todas las muestras excepto en 4A (1 animal) y 5A (5 animales sin ciclosporina y 3 animales de los que recibieron ciclosporina) (p<0.05)

Apoptosis en trasplante de pulmón / Apoptosis in lung transplantation. Influence of lavage and reperfusion on the organ

Objetivo: Determinar el rol de la irrigación con soluciones de preservación, la reperfusión y el rechazo en la apoptosis pulmonar en un escenario de trasplante pulmonar. Material y método: Venticuatro cerdos Landrace con un peso de 15 a 30 kilogramos fueron usados como donantes y receptores en un modelo de trasplante pulmonar izquierdo, con 5 días de sobrevida. Las muestras se obtuvieron en la siguiente secuencia: 1A: Donante, pulmón izquierdo inmediatamente luego de la apertura del torax. 1B: donante, pulmón derecho, inmediatamente luego de la apertura del tórax. 2A: Donante pulmón izquierdo, inmediatamente luego de la irrigación del organo. 2B Donante, pulmón derecho, sin irrigar. 3A: Pulmón izquierdo implantado, 1 hora luego de reperfundido en el receptor . 3B: Pulmón derecho (nativo), 1 hora luego de reperfundido el pulmón donante en el receptor. 4A: Pulmón izquierdo, biopsia transbronquial a las 48 horas postrasplante. 4B: Pulmón derecho, biopsia transbronquial a las 48 horas postransplante. 5A: Púlmón izquierdo, 5º día postrasplante (sacrificio). Todos los pulmones fueron irrigados con solución de Euro-Collins fría (4Cº) durante la ablación. Seis receptores no recibieron inmunosupresión y otros 6 receptores recibieron 15 mg/KG/ día de ciclosporina intravenosa.

Survival and dementia: a 7-year follow-up of an Italian elderly population.

The objective of this study was to investigate the association between dementia and mortality in an elderly Italian population. Demented subjects were identified by a previous prevalence study of Alzheimer's disease (AD) and specific dementing disorders. The study sample included all inhabitants of Appignano aged 60 and over (778 subjects), and was followed-up over a period of about 7 years. Periodic records of dates of death were obtained from the Registry Office of Appignano. We found considerably higher mortality ratios for subjects previously diagnosed as having dementia syndrome (12.5% at 1 year and 81.3% at about 7 years) than for those who were non-demented (3.0% at 1 year and 21.5% at about 7 years). In the group of demented subjects (N = 48), we also investigated the influence of sex, age, and specific dementing disorders on mortality ratios. The percentage of demented subjects who died during the whole period of follow-up was higher among men than women (100% vs. 66.7%) and increased considerably with increasing age (50.0% for age class 60-69, 76.5% for age class 70-79, and 86.2% for age class 80+). Mortality of subjects with multi-infarct dementia (MID) and mixed dementia (MD) tended to be slightly higher than in subjects affected by AD. Our results are consistent with those reported in previous population-based studies on survival of dementia patients.