Search

By using deceptive experiments in which participants are informed that they received caffeine when, in fact, they received an inert substance (i.e., placebo), several investigations have demonstrated that exercise performance can be enhanced to a similar degree as a known caffeine dose. This ‘placebo effect’ phenomenon may be part of the mechanisms explaining caffeine’s ergogenicity in exercise. However, there is no study that has established whether the placebo effect of caffeine is also present for other benefits obtained with acute caffeine intake, such as enhanced fat oxidation during exercise. Therefore, the aim of this investigation was to investigate the placebo effect of caffeine on fat oxidation during exercise. Twelve young men participated in a deceptive double-blind cross-over experiment. Each participant completed three identical trials consisting of a step incremental exercise test from 30 to 80% of V.O2max. In the two first trials, participants ingested either 3 mg/kg of cellulose (placebo) or 3 mg/kg of caffeine (received caffeine) in a randomized order. In the third trial, participants were informed that they had received 3 mg/kg of caffeine, but a placebo was provided (informed caffeine). Fat oxidation rates were derived from stoichiometric equations. In received caffeine, participants increased their rate of fat oxidation over the values obtained with the placebo at 30%, 40%, 50%, and 60% of V.O2max (all p &lt, 0.050). In informed caffeine, participants increased their rate of fat oxidation at 30%, 40%, 50% 60%, and 70% of V.O2max (all p &lt, 0.050) over the placebo, while there were no differences between received versus informed caffeine. In comparison to placebo (0.32 ± 0.15 g/min), the rate of maximal fat oxidation was higher in received caffeine (0.44 ± 0.22 g/min, p = 0.045) and in informed caffeine (0.41 ± 0.20 g/min, p = 0.026) with no differences between received versus informed caffeine. However, the intensity at which maximal fat oxidation rate was obtained (i.e., Fatmax) was similar in placebo, received caffeine, and informed caffeine trials (42.5 ± 4.5, 44.2 ± 9.0, and 41.7 ± 10.5% of V.O2max, respectively, p = 0.539). In conclusion, the expectancy of having received caffeine produced similar effects on fat oxidation rate during exercise than actually receiving caffeine. Therefore, the placebo effect of caffeine is also present for the benefits of acute caffeine intake on substrate oxidation during exercise and it may be used to enhance fat oxidation during exercise in participants while reducing any risks to health that this substance may have.

Objective We aimed to analyze risk factors related to the development of delirium, aiming for early intervention in patients with greater risk. Material and methods Observational study, including prospectively collected patients treated in a single general ICU. These were classified into two groups, according to whether they developed delirium or not (screening performed using CAM-ICU tool). Demographics and clinical data were analyzed. Multivariate logistic regression analyses were performed to quantify existing associations. Results 1462 patients were included. 93 developed delirium (incidence: 6.3%). These were older, scored higher on the Clinical Frailty Scale, on the risk scores on admission (SAPS-3 and SOFA), and had a greater number of organ failures (OF). We observed more incidence of delirium in patients who (a) presented more than two OF (20.4%; OR 4.9; CI95%: 2.9–8.2), and (b) were more than 74 years old albeit having Conclusions The highest risk observed for developing delirium clustered in patients who presented more than 2 OF and patients over 74 years old. The detection of patients at high risk for developing delirium could imply a change in management and improved quality of care.

Objective To assess the antibody response in non-immunocompromised adults after two doses of BNT162b2. Methods Prospective, single-centre observational study in non-immunocompromised adults aged 18 years or more who received two doses of BNT162b2. The study contemplates analyses of serum samples collected 1.5, 3, 6, 9 and 12 months after the second dose of BNT162b2; results of the 1.5- and 3-month time-points are presented in this report. Antibodies against the receptor binding domain of the S1 subunit of the spike protein of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) (anti-RBD antibodies) were measured using a commercial quantitative immunoassay. A threshold of 4160 AU/mL (corresponding to an ID50 of 1:250) was used as surrogate marker for serum neutralizing activity. Results Of 273 hospital workers who received two doses of BNT162b2, 260 (95%) agreed to participate in the study; 2/260 (0.8%) were excluded because of immunocompromised conditions. At the time of this report, 230/258 (89%) participants (mean age 46.0 years (SD 11.4 years); 143/230 (62%) female; 87/230 (38%) male) had completed 3 months of follow up after the second dose of BNT162b2. Thirty-six (16%) of the 230 had documented mild SARS-CoV-2 infection before receiving the first dose of BNT162b2. Median (interquartile range (IQR)) anti-RBD titres 1.5 months after vaccination were 9356 (5844–16 876) AU/mL; 3 months after vaccination, median anti-RBD titres had declined to 3952 (2190–8561) AU/mL (p < 0.001). Of 199/230 (86.5%) participants who had anti-RBD titres above 4160 AU/mL 1.5 months after the second dose of BNT162b2, only 95/230 (41%) maintained anti-RBD titres above this level 3 months after vaccination (p < 0.001). Conclusions The decline of anti-RBD antibodies 3 months after the second dose of BNT162b2 is of concern because it raises the possibility of a short-lived humoral immunity after vaccination. Booster doses of BNT162b2 might be required to maintain high titres of anti-RBD antibodies over time. pre-print 161 KB

Producción Científica, Background: most of the research concerning the influence of genetics on endurance performance has been carried out by investigating target genes separately. However, endurance performance is a complex trait that can stem from the interaction of several genes. The objective of this study was to compare the frequencies of polymorphisms in target genes involving cardiorespiratory functioning in elite endurance athletes vs. non-athlete controls. Methods: genotypic frequencies were determined in 123 elite endurance athletes and in 122 non-athletes. Genotyping of ACE (rs4340), NOS3 (rs2070744 and rs1799983), ADRA2a (rs1800544 and rs553668), ADRB2 (rs1042713 and rs1042714), and BDKRB2 (rs5810761) was performed by polymerase chain reaction. The total genotype score (TGS: from 0 to 100 arbitrary units; a.u.) was calculated from the genotype score in each polymorphism. Results: the mean TGS in non-athletes (47.72 ± 11.29 a.u.) was similar to elite endurance athletes (46.54 ± 11.32 a.u., p = 0.415). The distribution of TGS frequencies were also similar in non-athletes and elite endurance athletes (p = 0.333). There was no TGS cut-off point to discriminate being elite endurance athletes. Conclusions: the genetic profile in the selected genes was similar in elite endurance athletes and in controls, suggesting that the combination of these genes does not determine endurance performance., Consejo Superior de Deportes de España (CSD) - (grant 15/UPB10/08)

post-print 228 KB

The consumption of energy drinks (e.g., containing caffeine and taurine) has increased over the last decade among adolescents and athletes to enhance their cognitive level and improve intellectual and athletic performance. Numerous studies have shown that drinking moderate doses of such drinks produces beneficial effects, as they considerably boost the sporting performance of elite athletes in various sports, including both endurance and explosive events. However, apart from their ergogenic effects, the regular consumption of energy drinks also increases blood pressure and consequently incites problems such as hypertension, tachycardia, and nervousness, all of which can lead to cardiovascular disorders. A potential positive correlation between genetics and the moderate consumption of energy drinks and athletic performance has recently been reported; notwithstanding, a better understanding of the genetic variants involved in metabolism is a key area for future research to optimize the dose of energy drink consumed and obtain the maximal ergogenic effect in elite sports. The aim of this literature review, therefore, is to present the results of recent studies, classifying them according to the differences in the associations between energy drinks and: (i) Athletic performance; (ii) cardiovascular risk factors while practicing sports; and (iii) genetic associations and future prospects between the consumption of energy drinks and performance. post-print 429 KB

Background and Objectives: The techniques directed to the cranial field in osteopathy are the most questioned due to the lack of scientific evidence. In osteopathic practice, manual palpation is essential and, therefore, measuring reliability is fundamental. The objective of this study is to assess the precision and objectification of an educational model in cranial osteopathy based on experience. Materials and Methods: A reliability study was conducted in a cadaver skull where a strain gauge was placed on the sphenobasilar synchondrosis (SBS) of the base of the skull. Three cranial osteopathic techniques (lateral compression, anteroposterior compression, and compression maneuver of the mastoids) were performed 25 times by osteopaths with different degrees of experience (5–10 years, 1–5 years, &lt, 1 year). Measurements were computed for each of the three techniques of each group in comparison with the osteopath with &gt, 15 years of experience. Data were analyzed to check for inter- and intra-observer reliability using intra-class correlation coefficients (ICC). Results: Reliability in osteopaths with 5–10 years’ experience (observer 1 and observer 2) performing all three techniques was higher (p &lt, 0.001) than the osteopath with &gt, 15 years’ experience. Little or no reliability were observed in osteopaths with less experience. Conclusions: The experience of the osteopaths determines the reliability and effectiveness of the cranial techniques, a fundamental part in objectifying these techniques. This model can help implement objective training in cranial osteopathy formation.

Objective Endoscopist-directed propofol (EDP) sedation is becoming more popular, with a reported safety and efficacy similar to anesthesiologist-administered propofol (AAP). The aim of this study is to compare the efficiency of EDP and AAP in patients of low-intermediate anesthetic risk. Methods A prospective cost-effectiveness comparison study was conducted. The costs of the endoscopic procedures in the EDP and AAP group were calculated using the full cost methodology after breaking down the endoscopic activity into relative value units to allocate costs in an equitable way. To determine the effectiveness, adverse events related to endoscopic sedation and the number of incomplete procedures were registered for the EDP group and compared with those published by anesthesiologists for AAP. Results A total of 1165 and 18 919 endoscopic procedures were, respectively, included in the EDP and AAP groups. The average costs of EDP vs. AAP for gastroscopy, colonoscopy and endoscopic ultrasound were O 182.81 vs. O 332.93, O 297.07 vs. O 459.76, and O 319.92 vs. O 485.12, respectively. No significant differences were detected regarding the rate of overall adverse events (4.43 vs. 4.46%) or serious adverse events (0 vs. 0.17%); the rate of arterial hypotension was significantly lower in the EDP group: 0.34 vs. 1.78% [odds ratio (OR), 0.19; 95% confidence interval (CI), 0.08-0.46] and the desaturation rate was significantly lower in the AAP group: 3.26 vs. 1.29% (OR, 2.58; 95% CI, 1.85-3.60). No significant differences were found in terms of incomplete examinations (0.17 vs. 0.14%). Conclusion In patients with low-intermediate anesthetic risk referred for an endoscopic examination, EDP appears to be more efficient than AAP.

Previous investigations have found that several genes may be associated with the interindividual variability to the ergogenic response to caffeine. The aim of this study is to analyze the influence of the genetic variations in CYP1A2 (&minus, 163C&thinsp, &gt, A, rs762551, characterized such as &ldquo, fast&rdquo, (AA genotype) and &ldquo, slow&rdquo, caffeine metabolizers (C-carriers)) and ADORA2A (1976T&thinsp, C, rs5751876, characterized by &ldquo, high&rdquo, (TT genotype) or &ldquo, low&rdquo, sensitivity to caffeine (C-carriers)) on the ergogenic response to acute caffeine intake in professional handball players. Thirty-one professional handball players (sixteen men and fifteen women, daily caffeine intake = 60 &plusmn, 25 mg&middot, d&minus, 1) ingested 3 mg&middot, kg&minus, 1&middot, body mass (bm) of caffeine or placebo 60 min before undergoing a battery of performance tests consisting of a countermovement jump (CMJ), a sprint test, an agility test, an isometric handgrip test, and several ball throws. Afterwards, the handball players performed a simulated handball match (2 &times, 20 min) while movements were recorded using inertial units. Saliva samples were analyzed to determine the genotype of each player for the &minus, A polymorphism in the CYP1A2 gene (rs762551) and for the 1976T&thinsp, C polymorphism in the ADORA2A gene (rs5751876). In the CYP1A2, C-allele carriers (54.8%) were compared to AA homozygotes (45.2%). In the ADORA2A, C-allele carriers (80.6%) were compared to TT homozygotes (19.4%). There was only a genotype x treatment interaction for the ball throwing from 7 m (p = 0.037) indicating that the ergogenic effect of caffeine on this test was higher in CYP1A2 AA homozygotes than in C-allele carriers. In the remaining variables, there were no genotype x treatment interactions for CYP1A2 or for ADORA2A. As a whole group, caffeine increased CMJ height, performance in the sprint velocity test, and ball throwing velocity from 9 m (2.8&ndash, 4.3%, p = 0.001&ndash, 0.022, effect size = 0.17&ndash, 0.31). Thus, pre-exercise caffeine supplementation at a dose of 3 mg&middot, bm can be considered as an ergogenic strategy to enhance some neuromuscular aspects of handball performance in professional handball players with low daily caffeine consumption. However, the ergogenic response to acute caffeine intake was not modulated by CYP1A2 or ADORA2A genotypes.

Previous investigations have found that several genes may be associated with the interindividual variability to the ergogenic response to caffeine. The aim of this study is to analyze the influence of the genetic variations in CYP1A2 (−163C > A, rs762551; characterized such as “fast” (AA genotype) and “slow” caffeine metabolizers (C-carriers)) and ADORA2A (1976T > C; rs5751876; characterized by “high” (TT genotype) or “low” sensitivity to caffeine (C-carriers)) on the ergogenic response to acute caffeine intake in professional handball players. Thirty-one professional handball players (sixteen men and fifteen women; daily caffeine intake = 60 ± 25 mg·d−1) ingested 3 mg·kg−1·body mass (bm) of caffeine or placebo 60 min before undergoing a battery of performance tests consisting of a countermovement jump (CMJ), a sprint test, an agility test, an isometric handgrip test, and several ball throws. Afterwards, the handball players performed a simulated handball match (2 × 20 min) while movements were recorded using inertial units. Saliva samples were analyzed to determine the genotype of each player for the −163C > A polymorphism in the CYP1A2 gene (rs762551) and for the 1976T > C polymorphism in the ADORA2A gene (rs5751876). In the CYP1A2, C-allele carriers (54.8%) were compared to AA homozygotes (45.2%). In the ADORA2A, C-allele carriers (80.6%) were compared to TT homozygotes (19.4%). There was only a genotype x treatment interaction for the ball throwing from 7 m (p = 0.037) indicating that the ergogenic effect of caffeine on this test was higher in CYP1A2 AA homozygotes than in C-allele carriers. In the remaining variables, there were no genotype x treatment interactions for CYP1A2 or for ADORA2A. As a whole group, caffeine increased CMJ height, performance in the sprint velocity test, and ball throwing velocity from 9 m (2.8–4.3%, p = 0.001–0.022, effect size = 0.17–0.31). Thus, pre-exercise caffeine supplementation at a dose of 3 mg·kg−1·bm can be considered as an ergogenic strategy to enhance some neuromuscular aspects of handball performance in professional handball players with low daily caffeine consumption. However, the ergogenic response to acute caffeine intake was not modulated by CYP1A2 or ADORA2A genotypes.

Objectives The aim of the study is to assess whether women who choose to use menopausal hormone therapy (MHT) have lower quality of life (QoL) than those who do not initiate it using Cervantes short form scale (C-SF), and analyze sociodemographic factors associated with lower QoL in women. Study design A cross-sectional descriptive observational study was made in four hundred and eighty women with climacteric symptoms. Results Mean age was 51.1 years. Two hundred and sixty-one women (54.3 %) started MHT. The sample´s global mean in C-SF score was 51.3 ± 13.9. Women who choose to use MHT have higher score in C-SF (lower QoL) than women who reject it (58.7 ± 15.9 vs 46.7 ± 12.8; p 30 BMI) (52.8 ± 13.5 vs 41.0 ± 8.2; p = 0.002); with previous malignancies (56.2 ± 18.2 vs 50.2 ± 13.5; p = 0.020) and without sexual activity (58.0 ± 25.4 vs 50.4 ± 13.1; p = 0.009. No differences were found in C-SF score with respect to tobacco habits or physical activity. In the multivariate analysis, the variable independently associated to lower QoL by C-SF (high score) was to be a woman who want to initiate MHT (p = 0.004). Conclusions Women who choose to use MHT due to menopausal symptoms have lower quality of life measured by C-SF scale. Women with early menopause, with no obesity (

Objective: to analyse maternal physiological changes in several areas (cardiovascular, metabolic, renal and hepatic) related to the regular practice of a supervised exercise program. Methods: This is an unplanned secondary analysis from a randomized controlled trial carried out in a single maternity unit in Madrid, Spain (NCT 02,756,143). From November 2014 to June 2015, 92 women were randomly assigned to perform a mild-moderate supervised exercise program during pregnancy (Intervention group, IG) or to continue with their routine pregnancy care (control group, CG). For the purpose of this study we collected clinical and analytical data (heart blood pressure, weight, blood glucose, AST, ALT, blood Creatinine and blood Uric acid) available from all obstetric visits and examined the differences between groups. Results: We did not find any differences in: pregnancy weight (IG: 11.4 ± 4.4 Kg vs. CG: 10.1 ± 5.3 Kg; p = 0.173); fasting glucose at 10+0–12+6 weeks (IG: 78.48±8.34 vs. CG: 76±13.26, p = 0.305) or at 34+0–36+4 weeks (IG: 73.25±10.27 vs CG: 73.45± 8.29,p = 0.920), and 50 gs glucose tolerance at 24+4–26+6weeks (IG: 116.23±35.07 vs CG: 116.36±25.98, p = 0.984); Aspartate-amino-transferase at 10+0–12+6 weeks (IG: 15.38±4.17 vs CG: 17.33±7.05, p = 0.124) and at 34+0–36+4 weeks (IG: 21.65±5.25 vs CG: 19.53±8.32, p = 0.165) or Alanine-amino- transferase at 10+0–12+6 weeks (IG: 27.50±10.63 vs CG: 28.27±11.77, p = 0.746) or at 34+0–36+4 weeks (IG: 22.93±9.23 vs CG: 20.84±13.49, p = 0.407); blood Creatinine concentrations at 34+0–36+4 weeks (IG: 0.595±0.401 vs CG: 0.575±0.100, p = 0.757) and blood uric acid concentrations at 34+0–36+4 weeks (IG: 3.526 ± 0.787 vs CG: 3.262±0.672, p = 0.218). Heart blood pressure was similar between groups except at 27+0–28+6 weeks, where systolic blood pressure was significantly lower in the CG in comparison to the IG (116.31±10.8 mmHg vs. 120.22 ± 10.3 mmHg, p = 0.010). Conclusion: Regular supervised exercise during pregnancy does not alter normal maternal physiology pre-print 609 KB

Objective: The aim of the study is to evaluate the knowledge that men have about menopause and to analyze whether sociodemographic aspects influence in this knowledge. Methods: 560 consecutive surveys were collected during 2019. The surveys were completed anonymously, voluntarily and without incentives by men. A maximum score of 45 points was considered for the knowledge analysis. Results: The mean age was 49.13 ± 11.1 years. The most frequent source of information to obtain knowledge about menopause were friends (61.4%). The mean of the questionnaire score was 20.69 ± 6.1. The most frequent symptoms associated with menopause were hot flashes and vaginal dryness (93.7%; 48%) and the best-known treatment to improve vaginal health was lubricants at 69.5%. The most common treatment men know for improving menopause symptoms was menopause hormone treatment; however, 27.9% of men think there is no treatment for menopause. Differences between ages in numbers and grades were found (p=0.032). The scores by levels of study showed statistically differences (primary school, high school, professional training and university education (men with a higher level of education had significantly more knowledge) (p=0.013). Differences were showed in men who obtained information from health staff with respect to other sources (p

[Background]: The genetic profile that is needed to define an endurance athlete has been studied during recent years. The main objective of this work is to approach for the first time the study of genetic variants in liver-metabolizing genes and their role in endurance performance by comparing the allelic and genotypic frequencies in elite endurance athletes to the non-athlete population., [Methods]: Genotypic and allelic frequencies were determined in 123 elite endurance athletes (75 professional road cyclists and 48 endurance elite runners) and 122 male non-athlete subjects (sedentary). Genotyping of cytochrome P450 family 2 subfamily D member 6 (CYP2D6 rs3892097), glutathione-S transferase mu isoform 1 (GSTM1), glutathione S-transferase pi (GSTP rs1695) and glutathione S-transferase theta (GSTT) genes was performed by polymerase chain reaction (PCR). The combination of the polymorphisms for the “optimal” polygenic profile has been quantified using the genotype score (GS)., [Results]: Statistical differences were found in the genetic distributions between elite endurance athletes and non-athletes in CYP2D6 (p < 0.001) and GSTT (p = 0.014) genes. The binary logistic regression model showed a favourable OR (odds ratio) of being an elite endurance runner against a professional road cyclist (OR: 2.403, 95% CI: 1.213–4.760 (p = 0.002)) in the polymorphisms studied., [Conclusions]: Genotypic distribution of liver-metabolizing genes in elite endurance athletes is different to non-athlete subjects, with a favourable gene profile in elite endurance athletes in terms of detoxification capacity., The present study has been funded by the Spanish Higher Council of Sports (CSD), through the project “Study and validation of genetic polymorphisms that predict a better performance in endurance sports” (15/UPB10/08).

Cross-sectional study to know if tracheostomy influences the time on mechanical ventilation and reduces the ICU stay in patients with SARS-CoV2. From February 14 to May 31, 2020, 29 patients: 23 men and 6 women, with an average age (SD) of 66.4 years (±6,2) required tracheostomy. The average intensive care unit (ICU) stay was 36 days [31–56.5]. The average days on mechanical ventilation was 28,5 days (±9.7). Mean time to tracheostomy was 15.2 days (±9.5) with an average disconnection time after procedure of 11.3 days (±7.4). The average hospital stay was 55 days [39–79]. A directly proportional relation between the number of days of MV and the number of days from ICU admission until tracheostomy showed a significant value of p = 0.008. For each day of delay in tracheostomy, the days of mechanical ventilation were increased by 0.6 days. There was no relation between days to tracheostomy and days to disconnection (p = 0.092). PaO2 / FiO2 (PAFI) before tracheostomy and Simplified Acute Physiology Score III (SAPS III) at admission presented a statistical relation with mortality, with an OR of 1.683 (95%CI; 0.926–2.351; p = 0.078) and an OR of 1.312 (CI95%: 1.011–1.703; p = 0.034) respectively. The length of stay in the ICU until the tracheostomy was not related to the risk of death (p = 0.682). PEEP and PaO2/FiO2 (PAFI) at admission and before tracheostomy and APACHE II, SAPS III and SOFA at admission did not show influence over time on MV. We conclude that the delay in tracheostomy increase the days on mechanical ventilation but does not influence stay or mortality., Highlights • For each day of delay in tracheostomy, the days of mechanical ventilation were increased by 0.6 days. • Timing of the tracheostomy did not influence days of disconnection from mechanical ventilation, ICU stay, or mortality. • There was no relationship between days to tracheostomy and days to disconnection. • Respiratory variables (PEEP and PaO2 / FiO2 on admission and before tracheostomy) and patient severity scales (APACHE II, SAPS III and SOFA on admission) did not show influence over time on mechanical ventilation. • The length of stay in the ICU until the tracheostomy was not related to the risk of death.

Purpose Ovarian cancer (OC) is the commonest cause of death by gynaecological cancer in developed countries. Peritoneal carcinomatosis (PC) complete debulking without residual disease of >1 cm is the best prognostic predictor in advanced OC. PC is assessed with Computed tomography (CT). CT accuracy and cytoreduction success predictive ability are limited. PET/CT is not an imaging standard for PC. PC shows high signal foci in Diffusion-weighted magnetic resonance imaging (DWI MRI). We assessed the diagnostic performance (DP) and tumour burden correlation of Whole body DWI with background suppression MRI (WB-DWIBS/MRI) in PC of suspected OC using the Peritoneal Cancer Index (PCI), referring to cytoreduction surgery as the standard reference. Method Fifty patients with suspicion of disseminated OC underwent cytoreduction and WB-DWIBS/MRI. The PCI scores tumour burden (0–3) in 13 anatomical regions (global range of 0–39). Two radiologists (Rad1/Rad2) assessed the PCI preoperatively and with surgical findings. We evaluated regional and global DP, the interobserver agreement (Cohen´s kappa coefficient), statistical differences (McNemar test) and tumour burden (Pearson’s test). Results 72% (36/50) were epithelial OC and 78% (39/50) achieved complete cytoreduction. Global-PCI correlation was 0.762 (Rad1) with DP: Sensitivity 0.84, specificity 0.89, accuracy 0.89, and kappa 0.41. Average global-PCI was 7. The pelvis and right hypochondrium showed the highest positive rate and DP, while the intestinal regions presented the lowest. Previous studies reported higher sensitivity than CT or PET/CT, although only a few used the PCI. Conclusions WB-DWIBS/MRI is reliable to depict, quantify and to predict complete cytoreductive surgery in OC PC. pre-print 2737 KB

Purpose The treatment of thrombosis in patients with antiphospholipid syndrome (APS) usually requires long-term anticoagulation with vitamin K antagonists. The effectiveness of direct oral anticoagulants (DOACs) in APS has not been fully addressed. The purpose of this research was to analyze the efficacy (thrombotic event–free time) and tolerability (bleeding events) of DOACs in patients with APS. Methods We performed a descriptive analysis of a systematic review of data from patients with APS treated with DOACs reported in the literature, via EMBASE, PubMed, and the European League Against Rheumatism and American College of Rheumatology congresses. After systematic review, a meta-analysis of data from clinical trials was performed. Findings A total of 728 patients, accounting for 731 courses of treatment with DOACs, were identified. The majority (48.3%) presented with triple anti-phospholipid antibody positivity. The prevalence of thrombosis during DOAC treatment was 13.9%. Analysis of risk factors for recurrent thrombosis suggested that a higher mean (SD) number of prior thrombotic events (1.80 [0.87] vs 1.67 [1.45]; P = 0.012), history of combined arterial and venous thrombosis (27.3% vs 9.2% [ P < 0.0001]; odds ratio [OR] = 3.72 [95% CI, 1.91–7.25]), previous treatment with LMWH (9.8% vs 1.1% [ P = 0.04]; OR = 9.95 [95% CI, 1.08–91.97]), use of immunosuppressant treatment (41.7% vs 12.7% [ P = 0.03]; OR = 4.9 [95% CI, 1.21–19.76]), and no reason to switch anticoagulant treatment other than patient's decision (32% vs 2.8% [ P = 0.001]; OR = 16.24 [95% CI, 3.16–83.52]) were associated with a high risk for re-thrombosis. Meta-Analysis did not show statistically relevant difference in risk of thrombosis or bleeding comparing warfarin with DOACs. Implications The findings from this systematic literature review and meta-analysis suggest that patients treated with DOACs and having risk factors such as history of recurrent thrombosis, a history of combined arterial and venous thrombosis, or a need for immunosuppressant treatment, may have higer ratio of thrombotic recurrence. There are limited data to inform decisions on the use of DOACs in patients with APS with different or no risk factors. pre-print 1,91 MB

Introduction: An important inverse relation between IUD use and risk of cervical cancer has been proved. Women who used IUD had half the risk of developing cervical cancer. The mechanism how IUD is a protector factor is still unknown. Could be improving the clearance of HPV infection or stopping progression to cancer from preneoplasic lesion. The aim of the study is to check if IUD increases HPV clearance, that is, checking if after 1 year HPV infection disappears in more patients using IUD than those not using it. Study design: This is a cohort case-control prospective study, carried out in Universitary Hospital La Zarzuela in Madrid, Spain, performed between October 2015 and April 2018. No pregnant women between 25–50 years old, with HPV cervical infection were enrolled. We separated the participants into two groups: an IUD group, with women starting using IUD and non IUD group, with women using any other contraceptive method or none. HPV genotyping of cervical cytology samples were performed initially on enrolment day and one year after. Results: 254 participants were enrolled at the beginning of the study, 85 in the IUD group and 169 in the control group (non IUD). 179 participants completed the study, 54 (31%) in IUD group and 120 participants in non IUD group (69%). 38 women from IUD group cleared HPV infection (69.5%) and 65 women from control group cleared it (54.2%) (p = 0.044). An association in logistic regression was observed in HPV clearance with different factors. Firstly, higher percentage of patients with IUD clear the HPV infection than those in control group significantly associated (OR = 0.698, CI 95%; 0.251–0.998, p = 0.046). Clearance was higher in patients with low-risk HPV infection comparing with high risk HPV (OR = 1.078, CI 95%; 1.126–4.6.281, p = 0.026) and in patients with only one HPV type than those with more than one (OR = 0.194, CI 95%; 0.084–0.403, p

[Background]: It was hypothesized that asthmatic patients with mutant alleles in the leukotriene pathway should not respond to leukotriene receptor antagonists and the concept of a tailored treatment is increasingly supported. [Methods]: Sixty-one patients (mean age 24.9 years, range 14-52) with moderate persistent asthma were clinical and immunological assess prior and after a 6-month treatment with montelukast. Tandem repeat polymorphisms were genotyped in the promoter (-147 to -176) of 5-lipoxygenase gene (ALOX5). [Results]: Thirty-two patients (52.5%) were homozygous for the five repeats allele; 17 (27.9%) were heterozygous (4/5 repeats) and 12 (19.7%) were homozygous for 4/4 repeats. After the montelukast treatment decrease number of asthma exacerbations, improvement of FEV1 and decreased use of β2 agonists was observed in patients with 5/5 or 4/5 repeats. Conversely, the patients with 4/4 repeats genotype did not modify these data after treatment. [Conclusions]: It was confirmed that ALOX5 promoter polymorphisms have a clear influence in montelukast response in atopic moderate persistent asthma patients. The genetic study could identify those patients most likely to respond to montelukast. © 2008 Elsevier Ltd. All rights reserved., This work has been partially sponsored by grants of Instituto de Salud Carlos III (PI05/1746) and Fundacion Sociedad Española de Alergia e Inmunología Clínica (2005).

Diagnostic methods based upon exclusive detection of haemagglutinin do not detect sequence variation in other gene segments of the Influenza A virus. A complementary approach is described based upon high-resolution melting curve analysis of the neuraminidase gene, an approach with the potential ability to detect small changes in the neuraminidase sequence without the need for specific probes.

Introduction Human host immune response following infection with the new variant of A/H1N1 pandemic influenza virus (nvH1N1) is poorly understood. We utilize here systemic cytokine and antibody levels in evaluating differences in early immune response in both mild and severe patients infected with nvH1N1. Methods We profiled 29 cytokines and chemokines and evaluated the haemagglutination inhibition activity as quantitative and qualitative measurements of host immune responses in serum obtained during the first five days after symptoms onset, in two cohorts of nvH1N1 infected patients. Severe patients required hospitalization (n = 20), due to respiratory insufficiency (10 of them were admitted to the intensive care unit), while mild patients had exclusively flu-like symptoms (n = 15). A group of healthy donors was included as control (n = 15). Differences in levels of mediators between groups were assessed by using the non parametric U-Mann Whitney test. Association between variables was determined by calculating the Spearman correlation coefficient. Viral load was performed in serum by using real-time PCR targeting the neuraminidase gene. Results Increased levels of innate-immunity mediators (IP-10, MCP-1, MIP-1 beta), and the absence of anti-nvH1N1 antibodies, characterized the early response to nvH1N1 infection in both hospitalized and mild patients. High systemic levels of type-II interferon (IFN-gamma) and also of a group of mediators involved in the development of T-helper 17 (IL-8, IL-9, IL-17, IL-6) and T-helper 1 (TNF-alpha, IL-15, IL-12p70) responses were exclusively found in hospitalized patients. IL-15, IL-12p70, IL- 6 constituted a hallmark of critical illness in our study. A significant inverse association was found between IL- 6, IL- 8 and PaO2 in critical patients. Conclusions While infection with the nvH1N1 induces a typical innate response in both mild and severe patients, severe disease with respiratory involvement is characterized by early secretion of Th17 and Th1 cytokines usually associated with cell mediated immunity but also commonly linked to the pathogenesis of autoimmune/inflammatory diseases. The exact role of Th1 and Th17 mediators in the evolution of nvH1N1 mild and severe disease merits further investigation as to the detrimental or beneficial role these cytokines play in severe illness., This work has been made by an international team pertaining to the Spanish-Canadian Consortium for the Study of Influenza Immunopathogenesis. The authors would like to thank Lucia Rico and Veronica Iglesias for their assistance in the technical development of the multiplex cytokine assays, to Bego a Nogueira for her technical support, and to Nikki Kelvin for language revision of this article. This work was possible thanks to the financial support obtained from the Ministry of Science of Spain and Consejeria de Sanidad Junta de Castilla y Leon, Programa de investigacion comisionada en gripe, GR09/0021, Programa para favorecer la incorporacion de grupos de investigacion en las Instituciones del Sistema Nacional de Salud, EMER07/050, and Proyectos en Investigacion Sanitaria, PI081236. CIHR, NIH and LKSF-Canada support DJK. This sponsorship made possible reagent acquisition and sample transportation between participant groups.

Introduction: Pandemic A/H1N1/2009 influenza causes severe lower respiratory complications in rare cases. The association between host immune responses and clinical outcome in severe cases is unknown. Methods: We utilized gene expression, cytokine profiles and generation of antibody responses following hospitalization in 19 critically ill patients with primary pandemic A/H1N1/2009 influenza pneumonia for identifying host immune responses associated with clinical outcome. Ingenuity pathway analysis 8.5 (IPA) (Ingenuity Systems, Redwood City, CA) was used to select, annotate and visualize genes by function and pathway (gene ontology). IPA analysis identified those canonical pathways differentially expressed (P < 0.05) between comparison groups. Hierarchical clustering of those genes differentially expressed between groups by IPA analysis was performed using BRB-Array Tools v.3.8.1. Results: The majority of patients were characterized by the presence of comorbidities and the absence of immunosuppressive conditions. pH1N1 specific antibody production was observed around day 9 from disease onset and defined an early period of innate immune response and a late period of adaptive immune response to the virus. The most severe patients (n = 12) showed persistence of viral secretion. Seven of the most severe patients died. During the late phase, the most severe patient group had impaired expression of a number of genes participating in adaptive immune responses when compared to less severe patients. These genes were involved in antigen presentation, B-cell development, T-helper cell differentiation, CD28, granzyme B signaling, apoptosis and protein ubiquitination. Patients with the poorest outcomes were characterized by proinflammatory hypercytokinemia, along with elevated levels of immunosuppressory cytokines (interleukin (IL)-10 and IL-1ra) in serum. Conclusions: Our findings suggest an impaired development of adaptive immunity in the most severe cases of pandemic influenza, leading to an unremitting cycle of viral replication and innate cytokine-chemokine release. Interruption of this deleterious cycle may improve disease outcome., This work has been developed by an international team pertaining to the Spanish-Canadian Consortium for the Study of Influenza Immunopathogenesis. The authors would like to thank also to the Nursery teams who kindly collected the samples. The authors would like to thank Nikki Kelvin for language revision of this article. The study was scientifically sponsored by the Spanish Society for Critical Care Medicine (SEMICYUC). Funding: MICCIN-FIS/JCYL-IECSCYL-SACYL (Spain): Programa de Investigacion Comisionada en Gripe, GR09/0021 EMER07/050 PI081236 RD07/0067. CIHR NIH-Sardinia Recherche-LKSF Canada support DJK.