Immune modulation via dendritic cells by the effect of Thymosin-alpha-1 on immune synapse in HCMV infection.

Tα1 (Thymosin-alpha-1) is a thymus-derived hormone that has been demonstrated to be effective on diverse immune cell subsets. The objective of this study was to determine the in vitro immunomodulatory effect of Tα1 in human cytomegalovirus (HCMV) infection. Dendritic cells (DCs) were isolated from peripheral blood mononuclear cells (PBMCs) by negative selection and cultured in the presence or absence of Tα1. The immunophenotyping of DCs was characterised by multiparametric flow cytometry assessing CD40, CD80, TIM-3 and PDL-1 markers, as well as intracellular TNFα production. Then, autologous CD4+ or CD8+ T-Lymphocytes (TLs) isolated by negative selection from PBMCs were co-cultured with DCs previously treated with Tα1 in the presence or absence of HCMV. Intracellular TNFα, IFNγ, IL-2 production, CD40-L and PD-1 expression were assessed through immunophenotyping, and polyfunctionality in total TLs and memory subsets were evaluated. The results showed that Tα1 increased CD40, CD80, TIM-3 and TNFα intracellular production while decreasing PDL-1 expression, particularly on plasmacytoid dendritic cells (pDCs). Therefore, Tα1 modulated the production of TNFα, IFNγ and IL-2 in both total and memory subsets of CD4+ and CD8+ TLs by upregulating CD40/CD40-L and downregulating PDL-1/PD-1 expression. Our study concludes that Tα1 enhances antigen-presenting capacity of DCs, improves TLs responses to HCMV infection, and enhances the polyfunctionality of CD8+ TLs. Consequently, Tα1 could be an alternative adjuvant for use in therapeutic cell therapy for immunocompromised patients.

The use of alpha 1 thymosin as an immunomodulator of the response against SARS-Cov2.

BACKGROUND: Since the beginning of SARS-CoV2 pandemic, the mortality rate among elderly patients (60-90 years) has been around 50%, so age has been a determining factor of a worse COVID-19 prognosis. Associated with age, the thymic function involution and depletion plays an important role, that could be related to a dysregulated and ineffective innate and adaptive immune response against SARS-CoV2. Our study aims to further in vitro effect of human Thymosin-alpha-1 (α1Thy) treatment on the immune system in population groups with different thymic function levels in the scenario of SARS-CoV2 infection. RESULTS: Activation markers such as CD40, CD80 and TIM-3 were upregulated in α1Thy presence, especially in plasmacytoid dendritic cells (pDCs) and, with increased TNFα production was observed compared to untreated condition. Co-cultures of CD4 + and CD8 + T cells with DCs treated with α1Thy in response to SARS-CoV2 peptides showed a decrease in the cytokine production compared to the condition without α1Thy pre-treated. A decrease in CD40L activation co-receptor expression in CD8 + LTs was also observed, as well as an increase in PD1 in CD4 + TLs expression in both age groups. In fact, there are no age-related differences in the immunomodulatory effect of the hormone, and it seems that effector memory and terminally differentiated memory T lymphocyte subsets were the most actively influenced by the immunomodulatory α1Thy effect. Finally, the polyfunctionality measured in SARS-CoV2 Specific-T cells response was maintained in α1Thy presence in total and memory subpopulations CD4 + and CD8 + T-cells, despite decreased proinflammatory cytokines production. CONCLUSION: The hormone α1Thy could reduce, through the modulation of DCs, the amount of proinflammatory cytokines produced by T cells. Moreover, α1Thy improve lymphocyte functionality and could become a beneficial therapeutic alternative as an adjuvant in SARS-CoV2 treatment either in the acute phase after infection or reinfection. In addition, the effect on the T immune response means that α1Thy can be incorporated into the vaccination regimen, especially in the most immunologically vulnerable individuals such as the elderly. SUBJECTS: Thymosin alpha 1, Dendritic cells, SARS-CoV2-specific T cells response, Immunomodulation.

Tailoring interfacial effect in multilayers with Dzyaloshinskii-Moriya interaction by helium ion irradiation.

We show a method to control magnetic interfacial effects in multilayers with Dzyaloshinskii-Moriya interaction (DMI) using helium (He[Formula: see text]) ion irradiation. We report results from SQUID magnetometry, ferromagnetic resonance as well as Brillouin light scattering results on multilayers with DMI as a function of irradiation fluence to study the effect of irradiation on the magnetic properties of the multilayers. Our results show clear evidence of the He[Formula: see text] irradiation effects on the magnetic properties which is consistent with interface modification due to the effects of the He[Formula: see text] irradiation. This external degree of freedom offers promising perspectives to further improve the control of magnetic skyrmions in multilayers, that could push them towards integration in future technologies.

Outcomes of an enhanced recovery after radical cystectomy program in a prospective multicenter study: compliance and key components for success.

OBJECTIVE: To investigate the effect of an Enhanced Recovery After Surgery (ERAS) program on complications and length of stay (LOS) after radical cystectomy (RC) and to assess if the number and type of components of ERAS play a key role on the decrease of surgical morbidity. MATERIALS AND METHODS: We analyzed the data of 277 patients prospectively recruited in 11 hospitals undergoing RC initially managed according to local practice (Group I) and later within an ERAS program (Group II). Two main outcomes were defined: 90-day complications rate and LOS. As secondary variables we studied 90-day mortality, 30-day readmission and transfusion rate. RESULTS: Patients in Group II had a higher use of ERAS measures (98.6%) than those in Group I (78.2%) (p < 0.05). Patients in Groups I and II experienced similar complications (70.5% vs. 66%, p = 0.42). LOS was not different between Groups I and II (12.5 and 14 days, respectively, p = 0.59). The risk of having any complication decreases for patients having more than 15 ERAS measures adopted [RR = 0.815; 95% confidence interval (CI) 0.667-0.996; p = 0.045]. Avoidance of transfusion and nasogastric tube, prevention of ileus, early ambulation and a fast uptake of a regular diet are independently associated with the absence of complications. CONCLUSIONS: Complications and LOS after RC were not modified by the introduction of an ERAS program. We hypothesize that at least 15 measures should be applied to maximize the benefit of ERAS.

[Evaluation of a follow-up program for diabetes after hospital discharge]. / Evaluación de un protocolo de seguimiento para diabetes tras el alta hospitalaria.

BACKGROUND: Given the higher rate of hospital admissions among diabetic patients, discharge should be used to optimize outpatient treatment. We evaluate a follow-up program for diabetic patients after hospital discharge to determine the evolution of glycemic control. METHOD: Retrospective collection of data on 375 diabetic patients enrolled in the follow-up program for optimization treatment: telephonic follow-up where treatment was adjusted if needed; and three months after discharge an in-person consultation was scheduled. Factors potentially associated with a 1% improvement in HbA1c were studied by multivariate logistic regression. RESULTS: Seventy-three percent of enrolled patients completed the follow-up program; each patient received an average of 4.6 phone calls. Globally, basal mean HbA1c was significantly lower three months later regarding the initial value (8.6 vs. 7.2%); the most relevant lowering was found in the group of hyper-glycemia by poor metabolic control (from 9.9 to 7.7%), combined hyperglycemia (from 9.3 to 7.3%) and debut (from 8.3 to 6.4%). Twenty percent of patients reported capillary hypoglycemia, with two severe events. A shorter duration of diabetes, absence of corticotherapy and absence of hypoglycemia during the follow-up period were independent predictors for a 1% reduction in three-months HbA1c. CONCLUSION: In patients whose treatment is changed on hospital discharge, a program allowing frequent treatment adjustment would improve HbA1c levels. These results could help to organize health resources more rationally.

Evaluación de un protocolo de seguimiento para diabetes tras el alta hospitalaria / Evaluation of a follow-up program for diabetes after hospital discharge

FUNDAMENTO: Ante la mayor tasa de hospitalizaciones de los pacientes con diabetes (DM), se recomienda aprovechar el momento del alta hospitalaria para optimizar su tratamiento ambulatorio. Evaluamos un protocolo de seguimiento tras el alta hospitalaria de pacientes con DM para conocer la evolución del control glucémico. MATERIAL Y MÉTODOS: Se recogieron de forma retrospectiva datos de los 375 pacientes diabéticos incluidos en el protocolo, basado en optimización del tratamiento previo, seguimiento telefónico con ajuste terapéutico intermedio durante tres meses y consulta presencial al final del periodo. Se estudiaron factores potencialmente relacionados con una disminución del 1% en la HbA1c final mediante regresión logística. RESULTADOS: El 73% de los pacientes incluidos completaron el seguimiento, recibiendo una media de 4,6 llamadas. Globalmente, la HbA1c se redujo significativamente a los tres meses respecto a la inicial (de 8,62 a 7,19%); los mayores descensos se observaron en pacientes con hiperglucemia por mal control metabólico previo (de 9,85 a 7,65%), hiperglucemia combinada (de 9,32 a 7,31%) y debut (de 8,29 a 6,36%). El 20,5 % de los pacientes presentaron hipoglucemia capilar, en dos casos grave. Un menor tiempo de evolución de la DM, la no necesidad de corticoterapia y la ausencia de hipoglucemias en el seguimiento fueron predictores independientes de una reducción de 1% en la HbA1c a los tres meses. CONCLUSIÓN: Un protocolo de seguimiento mediante contacto telefónico de pacientes con DM con cambios de tratamiento al alta hospitalaria, permite el ajuste frecuente de la dosis y mejora los niveles de HbA1c, lo que podría ayudar a distribuir los recursos asistenciales de forma más racional

BACKGROUND: Given the higher rate of hospital admissions among diabetic patients, discharge should be used to optimize outpatient treatment. We evaluate a follow-up program for diabetic patients after hospital discharge to determine the evolution of glycemic control. METHOD: Retrospective collection of data on 375 diabetic patients enrolled in the follow-up program for optimization treatment: telephonic follow-up where treatment was adjusted if needed; and three months after discharge an in-person consultation was scheduled. Factors potentially associated with a 1% improvement in HbA1c were studied by multivariate logistic regression. RESULTS: Seventy-three percent of enrolled patients completed the follow-up program; each patient received an average of 4.6 phone calls. Globally, basal mean HbA1c was significantly lower three months later regarding the initial value (8.6 vs. 7.2%); the most relevant lowering was found in the group of hyper-glycemia by poor metabolic control (from 9.9 to 7.7%), combined hyperglycemia (from 9.3 to 7.3%) and debut (from 8.3 to 6.4%). Twenty percent of patients reported capillary hypoglycemia, with two severe events. A shorter duration of diabetes, absence of corticotherapy and absence of hypoglycemia during the follow-up period were independent predictors for a 1% reduction in three-months HbA1c. CONCLUSION: In patients whose treatment is changed on hospital discharge, a program allowing frequent treatment adjustment would improve HbA1c levels. These results could help to organize health resources more rationally

¿Es la tuberculosis ganglionar una verdadera enfermedad tuberculosa? / Is lymph node tuberculosis a true tuberculosis disease?

Introducción: La presencia de adenopatías intratorácicas es el patrón característico de la tuberculosis pediátrica. Puede interpretarse como una infección o una enfermedad tuberculosa, con las consiguientes diferencias terapéuticas. El objetivo de este estudio fue determinar si los pacientes con adenopatías intratorácicas aisladas presentan diferencias clínicas, diagnósticas y microbiológicas respecto a los pacientes con otras formas de enfermedad tuberculosa. Material y métodos: Se estudiaron todos los pacientes menores de 14 años diagnosticados de enfermedad tuberculosa en Cantabria entre 2005 y 2014. Se clasificaron en dos grupos: pacientes con adenopatías intratorácicas exclusivamente y pacientes que presentaron otras formas de tuberculosis. Se compararon entre ambos grupos los síntomas clínicos, la velocidad de sedimentación globular, el resultado de la prueba de la tuberculina (PT) y el aislamiento microbiológico. Resultados: Se diagnosticaron 81 pacientes con enfermedad tuberculosa. El 38,3% presentó tuberculosis ganglionar intratorácica y el resto otras formas de tuberculosis. La media de edad ± desviación estándar en el momento del diagnóstico fue de 70,46 ± 43,6 meses. Los pacientes con tuberculosis ganglionar resultaron asintomáticos con mayor frecuencia y presentaron diámetros de induración de la PT significativamente mayores. El aislamiento microbiológico se consiguió en un 25,9% del total. No se observaron diferencias significativas en el aislamiento microbiológico entre ambos grupos (el 35,5 frente al 16,13%; p= 0,074). En ningún paciente con adenopatías detectadas mediante tomografía computarizada se aisló Mycobacterium tuberculosis. Discusión: El aislamiento de M. tuberculosis constituye el gold standard para el diagnóstico de enfermedad tuberculosa, estableciendo el diagnóstico diferencial con la infección. En este estudio, los pacientes con tuberculosis ganglionar presentaron un porcentaje de aislamiento microbiológico similar a los pacientes con otras formas de tuberculosis. Según estos resultados, el aislamiento microbiológico de las tuberculosis ganglionares no sería un hallazgo casual, por lo que las formas ganglionares deberían considerarse una enfermedad en lugar de una infección tuberculosa

Introduction: The presence of intrathoracic lymph nodes is the characteristic pattern of pediatric tuberculosis but can be interpreted as infection or tuberculosis disease with different therapeutic approaches. The aim of this study was to determine if patients with isolated intrathoracic lymph nodes had clinical, diagnostic and microbiological features compared with patients diagnosed with other forms of tuberculosis disease. Material and methods: All patients younger than 14 years of age diagnosed with tuberculosis in Cantabria between 2005 and 2014 were included in the study. They were classified into two groups: patients with exclusively intrathoracic adenopathies and those with other forms of tuberculosis. Clinical symptoms, erythrocyte sedimentation rate, tuberculin skin test (TST) results and microbiological isolation between the two groups were compared. Results: A total of 81 patients were diagnosed with tuberculosis, 38.3% had nodal tuberculosis and the rest other forms of tuberculosis. The mean age at diagnosis was 70.46 ± 43.6 months. Patients with nodal tuberculosis were more frequently asymptomatic and had significantly higher TST induration diameters. Microbiological isolation was achieved in 25.9% of the patients and no significant differences in microbiological isolation between the two groups were observed (35.5 vs. 16.13%; p= 0.074). No Mycobacterium tuberculosis was isolated in any patient with lymphadenopathies detected by computed tomography. Discussion: The microbiological isolation is the gold standard of tuberculosis disease. Isolation of M. tuberculosis was not significantly superior in the group of patients with exclusive lymph node tuberculosis suggesting that lymph node tuberculosis should be considered a true tuberculosis disease

Toll-Like Receptor 7 (TLR-7) and TLR-9 Agonists Improve Hepatitis C Virus Replication and Infectivity Inhibition by Plasmacytoid Dendritic Cells.

Plasmacytoid dendritic cells (pDCs) are innate immune cells with high antiviral activity triggered by Toll-like receptor 7 (TLR-7) and TLR-9 stimulation. Moreover, they are important mediators between innate and adaptive immunity. Although nowadays there is available an effective therapeutic arsenal against hepatitis C virus (HCV), a protective vaccine is not available. We have analyzed the pDCs' response to HCV infection in a hepatitis C virus (HCV)-Huh7.5 virus-cell system, which allows completion of the virus infectious cycle. pDCs were cocultured following human immunodeficiency virus (HIV) aldrithiol-2 (AT-2 [TLR-7 agonist]) inactivation and CpG (TLR-9 agonist) stimulation. We employed three virus derivatives-wild-type Jc1, interferon (IFN)-resistant virus IR, and high-replicative-fitness virus P100-in order to explore additional IFN-α-related virus inhibition mechanisms. pDCs inhibited HCV infectivity and replication and produced IFN-α. After TLR-7 and TLR-9 stimulation, inhibition of infectivity and IFN-α production by pDCs were enhanced. TLR-7 stimulation drove higher TNF-related apoptosis-inducing ligand (TRAIL) expression in pDCs. Additionally, TLR-7- and TLR-9-stimulated pDCs exhibited a mature phenotype, improving the antigen presentation and lymph node homing-related markers. In conclusion, pDCs could serve as a drug target against HCV in order to improve antiviral activity and as an enhancer of viral immunization.IMPORTANCE We implemented a coculture system of pDCs with HCV-infected hepatoma cell line, Huh7.5. We used three HCV derivatives in order to gain insight into pDCs' behavior against HCV and associated antiviral mechanisms. The results with this cell coculture system support the capacity of pDCs to inhibit HCV replication and infectivity mainly via IFN-α, but also through additional mechanisms associated with pDC maturation. We provided evidence that TLR agonists can enhance antiviral pDCs' function and can induce phenotypic changes that may facilitate the interplay with other immune cells. These findings suggest the possibility of including TLR agonists in the strategies of HCV vaccine development.

Relevancia del síndrome piramidal en la esclerosis lateral amiotrófica / Relevance of the pyramidal syndrome in amyotrophic lateral sclerosis

Introducción: Los signos piramidales (hiperreflexia, espasticidad, signo de Babinski) son fundamentales para el diagnóstico de esclerosis lateral amiotrófica (ELA). Sin embargo, no siempre están presentes al comienzo, pueden variar con el tiempo y es controvertido su papel en la evolución. El objetivo del estudio es describir qué signos piramidales están presentes inicialmente y cómo evolucionan en una cohorte de pacientes con ELA, así como su papel pronóstico. Métodos: Análisis retrospectivo de pacientes recogidos de manera prospectiva, diagnosticados de ELA en nuestro centro, desde 1990 hasta 2015. Resultados: Del total de 130 pacientes con ELA, 34 (26,1%) no presentaron inicialmente ningún signo piramidal, mientras que 15 (11,5%) presentaban un síndrome piramidal completo. De aquellos pacientes sin piramidalismo inicial, la mediana de aparición de los primeros signos fue de 4,5 meses. El signo de Babinski estaba presente en 64 (49,2%), la hiperreflexia en 90 (69,2%) y en 22 (16,9%) pacientes existía espasticidad. Los signos piramidales tendían a mantenerse inalterados en el tiempo, aunque existe un porcentaje de pacientes en el que aparecen tardíamente o desaparecen con el tiempo. No se encontró asociación entre supervivencia y la presencia o modificación de signos piramidales, aunque la disminución de la espasticidad se asociaba a mayor deterioro clínico (escala ALSFR) (p < 0,001). Conclusión: Una cuarta parte de pacientes con ELA no presentaron inicialmente ningún signo piramidal y, en algunos casos, estos desaparecen con el tiempo. Esto resalta la necesidad de la inclusión de herramientas para la valoración de la vía piramidal (AU)

Introduction: Pyramidal signs (hyperreflexia, spasticity, Babinski sign) are essential for the diagnosis of amyotrophic lateral sclerosis (ALS). However, these signs are not always present at onset and may vary over time, besides which their role in disease evolution is controversial. Our goal was to describe which pyramidal signs were present and how they evolved in a cohort of patients with ALS, as well as their role in prognosis. Methods: Retrospective analysis of prospectively collected patients diagnosed with ALS in our centre from 1990 to 2015. Results: Of a total of 130 patients with ALS, 34 (26.1%) patients showed no pyramidal signs at the first visit while 15 (11.5%) had a complete pyramidal syndrome. Of those patients without initial pyramidal signs, mean time of appearance of the first signs was 4.5 months. Babinski sign was positive in 64 (49.2%) patients, hyperreflexia in 90 (69.2%) and 22 (16.9%) patients had spasticity. Pyramidal signs tended to remain unchanged over time, although they seem to appear at later stages or even disappear with time in some patients. We found no association between survival and the presence of changes to pyramidal signs, although decreased spasticity was associated with greater clinical deterioration (ALSFR scale) (P < .001). Conclusion: A quarter of patients with ALS initially showed no pyramidal signs and in some cases they even disappear over time. These data support the need for tools that assess the pyramidal tract (AU)

Relevance of the pyramidal syndrome in amyotrophic lateral sclerosis. / Relevancia del síndrome piramidal en la esclerosis lateral amiotrófica.

INTRODUCTION: Pyramidal signs (hyperreflexia, spasticity, Babinski sign) are essential for the diagnosis of amyotrophic lateral sclerosis (ALS). However, these signs are not always present at onset and may vary over time, besides which their role in disease evolution is controversial. Our goal was to describe which pyramidal signs were present and how they evolved in a cohort of patients with ALS, as well as their role in prognosis. METHODS: Retrospective analysis of prospectively collected patients diagnosed with ALS in our centre from 1990 to 2015. RESULTS: Of a total of 130 patients with ALS, 34 (26.1%) patients showed no pyramidal signs at the first visit while 15 (11.5%) had a complete pyramidal syndrome. Of those patients without initial pyramidal signs, mean time of appearance of the first signs was 4.5 months. Babinski sign was positive in 64 (49.2%) patients, hyperreflexia in 90 (69.2%) and 22 (16.9%) patients had spasticity. Pyramidal signs tended to remain unchanged over time, although they seem to appear at later stages or even disappear with time in some patients. We found no association between survival and the presence of changes to pyramidal signs, although decreased spasticity was associated with greater clinical deterioration (ALSFR scale) (P<.001). CONCLUSION: A quarter of patients with ALS initially showed no pyramidal signs and in some cases they even disappear over time. These data support the need for tools that assess the pyramidal tract.

[Results of the implementation of a protocol for outpatient management of the paediatric patient with tuberculosis]. / Resultados de la implantación de un protocolo para el manejo ambulatorio del paciente pediátrico con enfermedad tuberculosa.

OBJECTIVE: To assess the results of the implementation of a protocol for the outpatient management of paediatric patients with tuberculosis, and to compare it with the previous approach. MATERIAL AND METHODS: All patients younger than 14 years of age diagnosed with tuberculosis in Cantabria between 2005 and 2014 were included in the study. The pre-implementation period included patients admitted for gastric aspirate collection and to start treatment until 2010 (Pre-group). The post-implementation period was from 2010 onwards, using a protocol established for the outpatient management of these patients, with admission only being for clinical or social reasons, post-implantation period (Post-group). RESULTS: A total of 82 patients were studied: 29 from the Pre-group and 53 from Post-group. The median age was 61 months (IQR 32.5-97.75). All patients in the Pre-group were systematically admitted, compared to 26.4% of the Post-group (P<.001). The mean hospital stay was higher (7.27±7.1 days) in the Pre-group than in Post-group (3.4±11.46 days) (P<.0001). Only in 6.9% of patients from Pre-group were the 3 microbiological samples recommended for diagnosis following the international guidelines were provided, whereas they were provided by 73.58% patients from Post-group (P<.001). Of the cultures performed, 26.6% were positive for Mycobacterium tuberculosis, 37.5% of the Pre-group and 21.6% of the Post-group (P=.121). No significant differences were observed between the groups in other parameters related to treatment such as, therapeutic adherence, treatment not adjusted to the guidelines, treatment withdrawal or relapse.. DISCUSSION: Although guidelines recommend three microbiological samples for culture, no superior microbiological isolation was detected despite the increased number of samples collected. The management in hospital clinics of patients with suspected tuberculosis with stable clinical situation show similar or better clinical and microbiological results to the previous management, with lower hospital admission rate and with the subsequent cost savings.

Increased CD127+ and decreased CD57+ T cell expression levels in HIV-infected patients on NRTI-sparing regimens.

BACKGROUND: NRTIs-sparing regimens exert favourable profiles on T-cell homeostasis associated parameters. Our aim was to analyze the effect of NRTIs sparing regimen (NRTI-sparing-cART) vs NRTIs-containing regimen (NRTI-cART), on T-cell homeostasis associated parameters in naive HIV-infected patients. METHODS: Biomarkers of cell survival (CD127) and replicative senescence (CD57), were measured by multiparametric flow cytometry for T-cell phenotyping on peripheral blood mononuclear cells (PBMCs) samples just before (baseline) and after 48 weeks of undetectable viral load in patients on NRTI-sparing-cART (N = 13) and NRTI-cART (N = 14). After 48 weeks a subgroup of patients (n = 5) on NRTI-cART switched to NRTI-sparing-cART for another additional 48 weeks. In vitro assays were performed on PBMCs from HIV-uninfected healthy donors exposed or not to HIV. To analyze the independent factors associated with type of cART bivariate and stepwise multivariate analysis were performed after adjusting for basal CD4+, CD8+ and nadir CD4+ T-cell counts. RESULTS: After 48 weeks of a NRTI-sparing-cART vs NRTI-cART patients have higher effector memory (EM) CD4+ CD127+ T-cell levels, lower EM CD4+ CD57+ T-cell levels, higher CD8+ CD127+ T-cell levels, lower CD8+ CD57+ T-cell levels and higher memory CD8+ T-cell levels. This effect was confirmed in the subgroup of patients who switched to NRTI-sparing-cART. In vitro assays confirmed that the deleterious effect of a NRTIs-containing regimen was due to NRTIs. CONCLUSIONS: The implementation of NRTI-sparing regimens, with a favourable profile in CD127 and CD57 T-cell expression, could benefit cART-patients. These results could have potential implications in a decrease in the number of Non-AIDS events.

Surgery for pancreatic ductal adenocarcinoma

Surgical resection is the only potentially curative option in the treatment of pancreatic ductal adenocarcinoma. Preoperative radiological imaging allows to rule out the presence of metastases. Three resectability categories are established based on the radiological findings depending on the degree of contact between the tumor and the blood vessels. Histological confirmation of malignancy is only required in cases of borderline or non-resectable tumors, prior to neoadjuvant treatment initiation. Diagnostic laparoscopy is recommended in the presence of large tumors of the body or tail and in borderline tumors to explore the possibility of resection and to apply treatment with curative intent, as well as in those cases with high level of biomarkers to rule out peritoneal involvement. Prior to surgery preoperative nutritional measures as well as endoscopic biliary drainage can be applied to optimize patient’s conditions. Cephalic pancreaticoduodenectomy is the recommended surgical technique in tumors located in the head of the pancreas. The benefits from pyloric preservation, type or reconstruction (one vs. two loops), type of anastomosis (pancreaticojejunostomy vs. pancreaticogastrostomy), intraoperative biopsy of the pancreatic resection margin or the use of intraperitoneal drainages are inconclusive. Total pancreatectomy and/or portal resection should only be performed in particular cases; however, arterial resections have shown no benefits. Radical antegrade modular pancreaticosplenectomy, that can be performed laparoscopically, is the technique used for those tumors located in the pancreatic body-tail (AU)

No disponible

[Quality of life and associated characteristics of restless legs syndrome in the adult population of Burgos, Spain]. / Calidad de vida y caracteristicas asociadas del sindrome de piernas inquietas en la poblacion adulta de Burgos, España.

INTRODUCTION: Restless legs syndrome (RLS) is a neurological disorder with a prevalence of up to 15%, although little is known about its impact upon quality of life. AIM: To analyse the impact of RLS on health-related quality of life. SUBJECTS AND METHODS: A descriptive cross-sectional study. A random sample of 1,275 subjects over 18 years old, stratified by age, was taken from the urban area of Burgos, with an estimated prevalence, 10%; alpha, 5%; accuracy, 3%; and losses, 70%, using a two-phase study (screening and diagnosis of cases of RLS and non-cases confirmed by a doctor). The clinical and sociodemographic data were collected by means of semi-structured questionnaires, the European Quality of Life-5 Dimensions, the Restless Legs Syndrome Quality of Life Questionnaire, the Epworth Scale, the Goldberg Scale, the Sleep Scale and the International Restless Legs Syndrome Rating Scale. RESULTS: The prevalence of RLS was 5.6% (CI 95%: 2.5-8.7%). Of the total number of cases, 79.4% were women and only 7% had been previously diagnosed with RLS. Intense pain, insomnia and depression-anxiety were more frequent among the cases of RLS than in the controls (p < 0.001 in the three cases). The quality of life among the cases of RLS, especially in women, was poorer than among the controls (p < 0.001). For 11.7% of the cases, RLS made it difficult for the patients to work. CONCLUSIONS: RLS is associated with depression-anxiety, with a significant impact on sleep, on social and work relationships, and on the health-related quality of life.

TITLE: Calidad de vida y caracteristicas asociadas del sindrome de piernas inquietas en la poblacion adulta de Burgos, España.Introduccion. El sindrome de piernas inquietas (SPI) es un trastorno neurologico con una prevalencia de hasta un 15%, cuyo impacto sobre la calidad de vida resulta poco conocido. Objetivo. Analizar el impacto del sindrome de piernas inquietas (SPI) en la calidad de vida relacionada con la salud. Sujetos y metodos. Estudio descriptivo transversal. Se incluyo una muestra aleatoria, estratificada por edad, de 1.275 sujetos mayores de 18 años en el area urbana de Burgos, con las estimaciones de prevalencia, 10%; alfa, 5%; precision, 3%; y perdidas, 70%, usando un estudio en dos fases (cribado y confirmacion diagnostica de casos de SPI y no casos por un medico). Los datos clinicos y sociodemograficos se recogieron usando cuestionarios semiestructurados: European Quality of Life-5 Dimensions, Restless Legs Syndrome Quality of Life Questionnaire, escala de Epworth, escala de Goldberg, escala del sueño y cuestionario internacional del sindrome de piernas inquietas. Resultados. La prevalencia del SPI fue del 5,6% (IC 95%: 2,5-8,7%). El 79,4% de los casos eran mujeres; solo el 7% tenia un diagnostico previo de SPI. El dolor intenso, el insomnio y la depresion-ansiedad fueron mas frecuentes en los pacientes con SPI que en los controles (p < 0,001 en los tres casos). La calidad de vida entre los pacientes con SPI, especialmente en las mujeres, fue peor que en los controles (p < 0,001). En el 11,7% de los casos, el SPI produjo dificultades para trabajar. Conclusiones. El SPI esta asociado con ansiedad-depresion, con un significativo impacto en el sueño, en las relaciones sociales y laborales, y en la calidad de vida relacionada con la salud.

Surgery for pancreatic ductal adenocarcinoma.

Surgical resection is the only potentially curative option in the treatment of pancreatic ductal adenocarcinoma. Preoperative radiological imaging allows to rule out the presence of metastases. Three resectability categories are established based on the radiological findings depending on the degree of contact between the tumor and the blood vessels. Histological confirmation of malignancy is only required in cases of borderline or non-resectable tumors, prior to neoadjuvant treatment initiation. Diagnostic laparoscopy is recommended in the presence of large tumors of the body or tail and in borderline tumors to explore the possibility of resection and to apply treatment with curative intent, as well as in those cases with high level of biomarkers to rule out peritoneal involvement. Prior to surgery preoperative nutritional measures as well as endoscopic biliary drainage can be applied to optimize patient's conditions. Cephalic pancreaticoduodenectomy is the recommended surgical technique in tumors located in the head of the pancreas. The benefits from pyloric preservation, type or reconstruction (one vs. two loops), type of anastomosis (pancreaticojejunostomy vs. pancreaticogastrostomy), intraoperative biopsy of the pancreatic resection margin or the use of intraperitoneal drainages are inconclusive. Total pancreatectomy and/or portal resection should only be performed in particular cases; however, arterial resections have shown no benefits. Radical antegrade modular pancreaticosplenectomy, that can be performed laparoscopically, is the technique used for those tumors located in the pancreatic body-tail.

HLA-B*57 and IFNL4-related polymorphisms are associated with protection against HIV-1 disease progression in controllers.

Background: HIV-1-controllers maintain HIV-1 viremia at low levels (normally <2000 HIV-RNA copies/mL) without antiretroviral treatment. However, some HIV-1-controllers have evidence of immunologic progression with marked CD4+T-cell decline. We investigated host genetic factors associated with protection against CD4+T-cell loss in HIV-1-controllers. Methods: We analysed the association of interferon lambda 4 (IFNL4)-related polymorphisms and HLA-B haplotypes within Long Term Non-Progressor HIV-1-controllers ((LTNP-C), defined by maintaining CD4+T-cells counts >500 cells/mm3 for more than 7 years after HIV-1 diagnosis) versus non-LTNP-C, who developed CD4+T-cells counts <500 cells/mm3 Both a Spanish study cohort (n=140) and an international validation cohort (n=914) were examined. Additionally, in a subgroup of individuals HIV-1-specific T-cell responses and soluble cytokines were analysed RESULTS: HLA-B*57 was independently associated with the LTNP-C phenotype (OR=3.056 (1.029-9.069) p=0.044 and OR=1.924 (1.252-2.957) p=0.003) while IFNL4 genotypes represented independent factors for becoming non-LTNP-C (TT/TT, ss469415590, OR=0.401 (0.171-0.942) p=0.036 or A/A, rs12980275, OR=0.637 (0.434-0.934) p=0.021) in the Spanish and validation cohort, respectively, after adjusting for sex, age at HIV-1 diagnosis, IFNL4-related polymorphisms and different HLA-B haplotypes. LTNP-C showed lower plasma IP-10 (p=0.019) and higher IFN-γ (p=0.02) levels than the HIV-1-controllers with diminished CD4+T-cell numbers. Moreover, LTNP-C exhibited higher quantities of IL2+CD57- and IFN-γ+CD57- HIV-1-specific CD8+T-cells (p=0.002 and 0.041, respectively) than non-LTNP-C. Conclusions: We have defined genetic markers able to segregate stable HIV-1-controllers from those who experience CD4+T-cell decline. These findings allow for identification of HIV-1-controllers at risk for immunologic progression, and provide avenues for personalized therapeutic interventions and precision medicine for optimizing clinical care of these individuals.