Restless legs syndrome in patients with high serum ferritin and normal iron levels

Trabajo presentado como póster en el 18.º Congreso de la European Sleep Research Society, celebrado en Innsbruck (Austria) en 2006Objetivo. Documentar la asociación entre síndrome de piernas inquietas (SPI) y concentraciones de ferritina elevadas en cinco pacientes. Pacientes y métodos. Estudiamos a cinco varones con una edad media de 59 años (rango: 36-73 años). Todos los pacientes fueron remitidos por SPI (dos de ellos donantes de sangre), en dos casos asociado a síndrome de apnea obstructiva del sueño. Se efectuaron registros videopolisomnográficos y se realizó una analítica para determinar los niveles de ferritina y hierro en plasma. Resultados. Los cinco pacientes presentaban criterios clínicos de SPI: parestesias en las pantorrillas asociadas a una necesidad imperiosa de mover las piernas, inquietud motora, agravamiento de los síntomas por la tarde y por la noche, mejoría con el movimiento, dificultad de conciliación del sueño y despertares nocturnos frecuentes. La exploración neurológica, el electroencefalograma, el electromiograma y la resonancia magnética cerebral fueron normales. Los registros videopolisomnográficos mostraron sueño nocturno fragmentado, reducción del tiempo total de sueño, escasa eficiencia, índice de apnea-hipopnea > 10/h en dos casos, y en los cinco casos, índice de movimientos periódicos de las piernas por hora de sueño > 5/h. En todos los casos los niveles de hierro sérico estaban dentro de los límites normales y la concentración de ferritina era elevada. Conclusiones. La asociación entre SPI con movimientos periódicos de las piernas durante el sueño, hierro sérico normal y ferritina elevada no se ha descrito previamente. El hallazgo de la disminución de concentración de ferritina en uno de los pacientes –meses más tarde del tratamiento con fármacos dopaminérgicos– apoya la implicación de un mecanismo dopaminérgico en la fisiopatología del SPIAim. To document the association between restless legs syndrome (RLS) and high ferritin levels in five patients. Patients and methods. The five patients were male, mean age: 59 years (range: 36-73 years). The patients were referred for RLS (two of them blood donors), in two cases associated with obstructive sleep apnea. Patients underwent a video-PSG recording. Serum iron and serum ferritin were determined. Results. All patients fulfilled the clinical criteria for RLS: leg paresthesias associated with an urge to move, motor restlessness, worsening of symptoms during the evening and night, and partial relief with activity, difficulty falling asleep, and presence of nocturnal awakenings due to RLS. Neurological examination, EEGs, EMGs and MRIs were normal. Video-PSGs recordings showed a disturbed and fragmented sleep with a reduction in total sleep time, low sleep efficiency, respiratory abnormalities with an apnea-hipopnea index > 10/h in two cases, and in all of them a periodic leg movements index > 5/h. The serum iron levels were within the normal range in all cases, whereas those in serum ferritin levels were high. Conclusions. To our knowledge the association of normal serum iron with high serum ferritin levels in patients diagnosed clinically and polygraphically as having RLS with periodic leg movements has not been described before. The notion of an involvement of a dopaminergic mechanism in the pathophysiology of RLS is supported by the decrease in the values of serum ferritin concentration observed in one patient during follow-up while being treated with dopaminergic agent

Sleep quality and sleep deprivation: relationship with academic performance in university students during examination period

The beginning of the university brings together maturational, psychosocial and academic changes that make university students more prone to suffer from insufficient or poor quality sleep, which can negatively influence their academic performance. The period of taking exams is a key part of the academic year. However, there are few studies that analyze sleep during this period of time. Our aim is to study the association of sleep quality and sleep deprivation with academic performance during the examination period. A descriptive, cross-sectional and correlational study was carried out with the participation of 640 subjects in the first three years of five faculties belonging to the Universidad Autónoma de Madrid. The instrument used consisted of a questionnaire that included sociodemographic and academic data, Pittsburgh Sleep Quality Index, Epworth Sleepiness Scale and information about the academic performance. During the examination period, a positive association was found between sleep quality and academic performance. University students slept less than desired, both on weekdays and weekends, and the sleep debt during the week was associated with a worse students’ perception of their academic performance. In total, 61.3% of the students believed that their performance would improve by getting more sleep. In addition, low drowsiness and napping were also found. In conclusion, during periods of greater academic demand, an insufficient sleep and poor quality is commonly observed, affecting negatively to their academic performance. Actually, about 2/3 of our subjects believed that their performance would improve by getting more slee

Clinical and polysomnographic predictors of the Natural History of poor sleep in the general population

Study Objectives: Approximately 8-10% of the general population suffers from chronic insomnia, whereas another 20-30% of the population has insomnia symptoms at any given time (i.e., poor sleep). However, few longitudinal studies have examined risk factors of the natural history of poor sleep, and none have examined the role of polysomnographic (PSG) variables. Design: Representative longitudinal study. Setting: Sleep laboratory. Participants: From a random, general population sample of 1,741 individuals of the adult Penn State Cohort, 1,395 were followed up after 7.5 yr. Measurements: Full medical evaluation and 1-night PSG at baseline and telephone interview at follow-up. Results: The rate of incident poor sleep was 18.4%. Physical (e.g., obesity, sleep apnea, and ulcer) and mental (e.g., depression) health conditions and behavioral factors (e.g., smoking and alcohol consumption) increased the odds of incident poor sleep as compared to normal sleep. The rates of persistent, remitted, and poor sleepers who developed chronic insomnia were 39%, 44%, and 17%, respectively. Risk factors for persistent poor sleep were physical health conditions combined with psychologic distress. Shorter objective sleep duration and a family history of sleep problems were risk factors for poor sleep evolving into chronic insomnia. Conclusions: Poor sleep appears to be primarily a symptom of physical and mental health conditions, whereas the persistence of poor sleep is associated with psychologic distress. Importantly, sleep apnea appears to be associated with incident poor sleep but not with chronic insomnia. Finally, this study suggests that objective short sleep duration in poor sleepers is a biologic marker of genetic predisposition to chronic insomniaThis research was funded in part by the National Institutes of Health grants RO1 51931, RO1 40916 (to Dr. Bixler), and RO1 64415 (to Dr. Vgontzas)

Possible role of highly activated mucosal NK cells against viral respiratory infections in children undergoing haematopoietic stem cell transplantation

Infection is the leading cause of non-relapse-related mortality after allogeneic haematopoietic stem cell transplantation (HSCT). Altered functions of immune cells in nasal secretions may influence post HSCT susceptibility to viral respiratory infections. In this prospective study, we determined T and NK cell numbers together with NK activation status in nasopharyngeal aspirates (NPA) in HSCT recipients and healthy controls using multiparametric flow cytometry. We also determined by polymerase chain reaction (PCR) the presence of 16 respiratory viruses. Samples were collected pre-HSCT, at day 0, +10, +20 and +30 after HSCT. Peripheral blood (PB) was also analyzed to determine T and NK cell numbers. A total of 27 pediatric HSCT recipients were enrolled and 16 of them had at least one viral detection (60%). Rhinovirus was the most frequent pathogen (84% of positive NPAs). NPAs of patients contained fewer T and NK cells compared to healthy controls (p = 0.0132 and p = 0.120, respectively). Viral PCR + patients showed higher NK cell number in their NPAs. The activating receptors repertoire expressed by NK cells was also higher in NPA samples, especially NKp44 and NKp46. Our study supports NK cells relevance for the immune defense against respiratory viruses in HSCT recipients.This work was supported in part by the National Health Service of Spain, Instituto de Salud Carlos III (ISCIII), FONDOS FEDER grant (FIS) PI18/01301, CRIS Foundation to Beat Cancer, Patients’ Support Associations Fundación Mari Paz Jiménez Casado and La Sonrisa de Álex and a Small Grant Award from the European Society for Paediatric Infectious Diseases.S

Anti-CXCR4 Antibody Combined With Activated and Expanded Natural Killer Cells for Sarcoma Immunotherapy

Sarcoma is one of the most severe forms of pediatric cancer and current therapies -chemotherapy and surgery- fail to eradicate the disease in half of patients. Preclinical studies combining new therapeutic approaches can be useful to design better therapies. On one hand, it is known that CXCR4 expression is implicated in rhabdomyosarcoma progression, so we analyzed relapses and chemotherapy-resistant rhabdomyosarcoma tumors from pediatric patients and found that they had particularly high levels of CXCR4 expression. Moreover, in assays in vitro, anti-CXCR4 blocking antibody (MDX1338) efficiently reduced migration and invasion of alveolar rhabdomyosarcoma RH30 cells. On the other hand, activated and expanded natural killer (NKAE) cell therapy showed high cytotoxicity against sarcoma cells in vitro and completely inhibited RH30 tumor implantation in vivo. Only the combination of MDX1338 and NKAE treatments completely suppressed metastasis in mice. In this study, we propose a novel therapeutic approach based on anti-CXCR4 blocking antibody in combination with NKAE cell therapy to prevent rhabdomyosarcoma tumor implantation and lung metastasis. These results provide the first evidence for the efficacy of this combined immunotherapy for preventing sarcoma disease dissemination.This work was supported in part by the National Health Service of Spain, Instituto de Salud Carlos III (ISCIII), FONDOS FEDER grant (FIS) PI15/00973; Asociacion Espanola Contra el Cancer to AP-M; CRIS Foundation to Beat Cancer grant to JV, LF, and AE; and Patients' Support Associations Fundacion Mari Paz Jimenez Casado and La Sonrisa de Alex to MV and the research project

Blood donations and transfusions during the COVID-19 pandemic in Spain: Impact according to autonomous communities and hospitals

Worldwide, the COVID-19 pandemic has caused a decline in blood donations, between 30% and 70% in some of the most affected countries. In Spain, during the initial eight weeks after the State of Emergency was decreed on 14 March 2020, in the weekly reports of the Health Ministry, an average decrease of 20% was observed between 11 and week 25 compared with the 2018 donation. We aimed to investigate the impact of the COVID-19 pandemic on blood donations and blood distribution in four autonomous communities, and to explore the evolution of the consumption of blood components (BCs) in ten hospitals of six autonomous communities. We performed a prospective study of grouped cohorts on the donation and distribution of blood in four regional transfusion centers in four autonomous communities in Spain, and a retrospective study of the consumption of blood components in ten hospitals in six autonomous communities. Regarding donations, there was no significant decrease in donations, with differences between autonomous communities, which started between 1 and 15 March 2020 (−11%). The increase in donations in phase II (from 26 May 2020) stands out. Regarding consumption, there was a significant reduction in the consumption of packed red blood cells (RBCs) (24.5%), plasma (45.3%), and platelets (25.3%) in the central period (16 March–10 May). The reduction in the consumption of RBCs was significant in the period from 1–15 March. Conclusions: The COVID-19 pandemic has affected the donation and consumption of BCs

Role of NAFLD on the Health Related QoL Response to Lifestyle in Patients With Metabolic Syndrome: The PREDIMED Plus Cohort

ObjectiveTo evaluate the effect of Non-alcoholic fatty liver disease (NAFLD) status in the impact of lifestyle over Health-related quality of life (HRQoL) in patients with metabolic syndrome (MetS). MethodsBaseline and 1 year follow up data from the PREDIMED-plus cohort (men and women, 55-75 years old with overweight/obesity and MetS) were studied. Adherence to an energy-restricted Mediterranean Diet (er-MeDiet) and Physical Activity (PA) were assessed with a validated screeners. Hepatic steatosis index (HSI) was implemented to evaluate NAFLD while the SF-36 questionnaire provided HRQoL evaluation. Statistical analyses were performed to evaluate the influence of baseline NAFLD on HRQoL as affected by lifestyle during 1 year of follow up. ResultsData from 5205 patients with mean age of 65 years and a 48% of female participants. Adjusted linear multivariate mixed regression models showed that patients with lower probability of NAFLD (HSI < 36 points) were more responsive to er-MeDiet (beta 0.64 vs beta 0.05 per er-MeDiet adherence point, p< 0.01) and PA (beta 0.05 vs beta 0.01 per MET-h/week, p = 0.001) than those with high probability for NAFLD in terms Physical SF-36 summary in the 1 year follow up. 10 points of er-MeDiet adherence and 50 MET-h/week were thresholds for a beneficial effect of lifestyle on HRQoL physical domain in patients with lower probability of NAFLD. ConclusionThe evaluation of NAFLD by the HSI index in patients with MetS might identify subjects with different prospective sensitivity to lifestyle changes in terms of physical HRQoL (http://www.isrctn.com/ISRCTN89898870)

Circulating carotenoids are associated with favorable lipid and fatty acid profiles in an older population at high cardiovascular risk

Carotenoid intake has been reported to be associated with improved cardiovascular health, but there is little information on actual plasma concentrations of these compounds as biomarkers of cardiometabolic risk. The objective was to investigate the association between circulating plasma carotenoids and different cardiometabolic risk factors and the plasma fatty acid profile. This is a cross-sectional evaluation of baseline data conducted in a subcohort (106 women and 124 men) of an ongoing multi-factorial lifestyle trial for primary cardiovascular prevention. Plasma concentrations of carotenoids were quantified by liquid chromatography coupled to mass spectrometry. The associations between carotenoid concentrations and cardiometabolic risk factors were assessed using regression models adapted for interval-censored variables. Carotenoid concentrations were cross-sectionally inversely associated with serum triglyceride concentrations [-2.79 mg/dl (95% CI: -4.25, -1.34) and -5.15 mg/dl (95% CI: -7.38, -2.93), p-values = 0.0002 and <0.00001 in women and men, respectively], lower levels of plasma saturated fatty acids [-0.09% (95% CI: -0.14, -0.03) and -0.15 % (95% CI: -0.23, -0.08), p-values = 0.001 and 0.0001 in women and men, respectively], and higher levels of plasma polyunsaturated fatty acids [(0.12 % (95% CI: -0.01, 0.25) and 0.39 % (95% CI: 0.19, 0.59), p-values = 0.065 and 0.0001 in women and men, respectively] in the whole population. Plasma carotenoid concentrations were also associated with higher plasma HDL-cholesterol in women [0.47 mg/dl (95% CI: 0.23, 0.72), p-value: 0.0002], and lower fasting plasma glucose in men [-1.35 mg/dl (95% CI: -2.12, -0.59), p-value: 0.001]. Keywords: Mediterranean diet; PREDIMED-plus study; cardiovascular health; liquid chromatography; mass spectrometry; plasma carotenoids

Treatment with tocilizumab or corticosteroids for COVID-19 patients with hyperinflammatory state: a multicentre cohort study (SAM-COVID-19)

Objectives: The objective of this study was to estimate the association between tocilizumab or corticosteroids and the risk of intubation or death in patients with coronavirus disease 19 (COVID-19) with a hyperinflammatory state according to clinical and laboratory parameters. Methods: A cohort study was performed in 60 Spanish hospitals including 778 patients with COVID-19 and clinical and laboratory data indicative of a hyperinflammatory state. Treatment was mainly with tocilizumab, an intermediate-high dose of corticosteroids (IHDC), a pulse dose of corticosteroids (PDC), combination therapy, or no treatment. Primary outcome was intubation or death; follow-up was 21 days. Propensity score-adjusted estimations using Cox regression (logistic regression if needed) were calculated. Propensity scores were used as confounders, matching variables and for the inverse probability of treatment weights (IPTWs). Results: In all, 88, 117, 78 and 151 patients treated with tocilizumab, IHDC, PDC, and combination therapy, respectively, were compared with 344 untreated patients. The primary endpoint occurred in 10 (11.4%), 27 (23.1%), 12 (15.4%), 40 (25.6%) and 69 (21.1%), respectively. The IPTW-based hazard ratios (odds ratio for combination therapy) for the primary endpoint were 0.32 (95%CI 0.22-0.47; p < 0.001) for tocilizumab, 0.82 (0.71-1.30; p 0.82) for IHDC, 0.61 (0.43-0.86; p 0.006) for PDC, and 1.17 (0.86-1.58; p 0.30) for combination therapy. Other applications of the propensity score provided similar results, but were not significant for PDC. Tocilizumab was also associated with lower hazard of death alone in IPTW analysis (0.07; 0.02-0.17; p < 0.001). Conclusions: Tocilizumab might be useful in COVID-19 patients with a hyperinflammatory state and should be prioritized for randomized trials in this situatio