Angiotensin II Receptor Blockers Reduce Tau/Aß42 Ratio: A Cerebrospinal Fluid Biomarkers' Case-Control Study.

(1) Background: The role of antihypertensives in Alzheimer's Disease (AD) prevention is controversial. This case-control study aims to assess whether antihypertensive medication has a protective role by studying its association with amyloid and tau abnormal levels. Furthermore, it suggests a holistic view of the involved pathways between renin-angiotensin drugs and the tau/amyloidß42 ratio (tau/Aß42 ratio); (2) Methods: The medical records of the participant patients were reviewed, with a focus on prescribed antihypertensive drugs and clinical variables, such as arterial blood pressure. The Anatomical Therapeutic Chemical classification was used to classify each drug. The patients were divided into two groups: patients with AD diagnosis (cases) and cognitively healthy patients (control); (3) Results: Age and high systolic blood pressure are associated with a higher risk of developing AD. In addition, combinations of angiotensin II receptor blockers are associated with a 30% lower t-tau/Aß42 ratio than plain angiotensin-converting enzyme inhibitor consumption; (4) Conclusions: Angiotensin II receptor blockers may play a potential role in neuroprotection and AD prevention. Likewise, several mechanisms, such as the PI3K/Akt/GSK3ß or the ACE1/AngII/AT1R axis, may link cardiovascular pathologies and AD presence, making its modulation a pivotal point in AD prevention. The present work highlights the central pathways in which antihypertensives may affect the presence of pathological amyloid and tau hyperphosphorylation.

[Effect of different schemes of androgen deprivation therapy on bone mass density in prostate cancer patients]. / Efecto de diferentes esquemas de terapia de deprivación androgénica sobre la densidad mineral ósea de pacientes con cáncer de próstata.

OBJECTIVES: To evaluate the aspects of the basal bone health status in prostate cancer patients. Furthermore, to evaluate in a real-world setting the effect of different schemes (intermittent or continuous) of androgen deprivation therapy (ADT) and the effect of denosumab in bone mass density (BMD). METHODS: Observational, retrospective study of a cohort of prostate cancer patients in treatment with luteinizing hormone-releasing hormone (LH-RH) agonists, evaluated in the rheumatology department of a tertiary center. Demographics, FRAX score, LH-RH treatment scheme, osteoporosis treatment, laboratory data and BMD were collected. Mixed effect regression models to analyze the interaction between LH-RH treatment scheme, denosumab and BMD evolution were used. RESULTS: Eighty-three patients (mean age 71±8years) were included. At the basal evaluation, 16% of patients presented densitometric osteoporosis and 27% of patients presented high fracture risk. Eighty percent of patients had inadequate vitaminD levels. VitaminD >30ng/mL was correlated with higher T-scores. There was no association between LH-RH treatment scheme and BMD evolution, however there was a positive association with denosumab. CONCLUSION: A high proportion of patients presented elevated fracture risk or inadequate vitaminD levels, not previously recognized. Bone health assessment and fracture risk evaluation are convenient in these patients. In a real-world setting, the effect of denosumab in BMD is detected, however the effect of intermittent LH-RH schema treatment is less evident.

How macronutrients and pancreatic enzyme supplements dose variability affect fat, protein and starch absorption in children with cystic fibrosis.

BACKGROUND: low evidence on the dose of enzymatic supplements used in pancreatic enzyme replacement therapy (PERT) is available. AIM: assessing if fat, protein and starch absorption could be related to the dose of the enzymatic supplement, the intra-patient variability in the dose and macronutrient intake. METHODS: Four-day food records and 3-day faecal samples were prospectively collected in 69 children with cystic fibrosis. Pearson correlations between enzyme dose and macronutrient absorption, and beta regression models were applied to explain the results. RESULTS: the supply of protease units per protein intake (PU/g protein) in relation to lipase units per fat intake (LU/g fat) was low and the intra-patient variability in the dose of enzymes was ±1331 LU/g fat. Fat and starch absorption was >90% while for protein it was 81.5%. The coefficient of fat absorption was associated with an interaction between the dose of LU/g fat and its variability among different days. Lipid and protein intake were also determinants of the coefficient of fat absorption. CONCLUSION: the dose of PERT should be re-adjusted to the amount of dietary fat of every meal (constant LU/g fat) to minimize variability and increase fat absorption. Also, the supply of protease should be increased to prevent from protein malabsorption.

Evolution in the incidence of infectious diseases in the pediatric ENT area during the COVID-19 pandemic.

INTRODUCTION: SARS COV-2 infection is an emerging disease that has become a global pandemic since the beginning of 2020. To reduce transmission, measures have been imposed by governments such as home confinement, the use of masks, social distancing or promotion of hand hygiene. The aim of this study is to determine if the measures adopted to reduce the COVID-19 pandemic have produced a decrease in the incidence of infectious diseases and their complications in the ENT area in our center. MATERIAL AND METHODS: A retrospective descriptive study was carried out in a tertiary hospital of patients aged between 0 and 15 years who required admission due to deep cervical infections, complications derived from acute otitis media (mastoiditis or facial paralysis) or complicated acute sinusitis. RESULTS: There is a notable decrease in the number of global admissions in the COVID period (9) compared to the average of the previous 5 years (20.1). Likewise, there are statistically significant differences in the number of admissions for cervical infections (p value=0.027) and complications derived from acute otitis media (p value=0.029). DISCUSSION/CONCLUSION: A decrease in the number of admissions caused by complications of infections in the ENT area in paediatric patients has been observed after the start of the COVID-19 pandemic in our environment, this fact could be explained by a global decrease in the number of infections of the upper respiratory tract due to the hygienic measures taken by the COVID-19 pandemic.

Real-world Effectiveness and Safety of JAK Inhibitors in Rheumatoid Arthritis: A Single-centre Study.

BACKGROUND/OBJECTIVE: To assess the effectiveness and safety of Baricitinib and Tofacitinib in rheumatoid arthritis (RA) patients in "real world" conditions. METHODS: A single centre retrospective study was performed including RA patients who had initiated treatment with Baricitinib or Tofacitinib from September-2017 to January-2020. Demographic, clinical, laboratory, efficacy and safety variables were collected from baseline and at months 1, 3, 6, 12, 18 and 24. Effectiveness was evaluated by changes from the baseline in DAS28, SDAI, HAQ and acute phase reactants. Safety analysis included adverse events due to any cause, including infection or intolerance. Infection was considered severe if it implied hospitalization. Statistical analysis consisted in Bayesian mixed ordinal regression models including the monotonic effect of each visit and Kaplan-Meier survival curves. RESULTS: Overall, 98 patients were included. A significant reduction of disease activity scores was noted in both groups. No difference between either treatment was detected in terms of effectiveness even in first line, after bDMARD failure, in monotherapy nor combined therapy. A total of 54 adverse events were recorded of which 18 were considered relevant. The incidence of infection, including Herpes Zoster, was similar in both groups. No patients in either group suffered any tuberculosis, thromboembolic event, malignancy, death or cardiovascular adverse events. Survival analysis did not show any difference between groups. CONCLUSION: Baricitinib and Tofacitinib are both comparable in terms of effectiveness and safety in real world conditions.

The association of salivary caffeine levels with serum concentrations in premature infants with apnea of prematurity.

The purpose of this paper is to verify whether the concentrations of caffeine in saliva are comparable to serum concentrations in preterm infants who are treated with caffeine for apnea of prematurity. This is a prospective observational study. Eligible participants were newborn infants < 37 weeks of gestational age treated with oral or intravenous caffeine for apnea of prematurity. Two paired samples of saliva and blood were collected per patient. Tube solid-phase microextraction coupled online to capillary liquid chromatography with diode array detection was used for analysis. A total of 47 infants with a median gestational age of 28 [26-30] weeks and a mean of 1.11 ± 0.4 kg of birth weight. Median postmenstrual age, when samples were collected, was 31 [29-33] weeks. Serum caffeine median levels of 19.30 µg/mL [1.9-53.90] and salivary caffeine median levels of 16.36 µg/mL [2.20-56.90] were obtained. There was a strong positive Pearson's correlation between the two variables r = 0.83 (p < 0.001). CONCLUSION: The measurement of salivary caffeine concentrations after intravenous or oral administration offers an alternative to serum caffeine monitoring in apnea of prematurity. Measurement of salivary concentration minimizes blood draws, improves blood conservation, and subsequently minimizes painful procedures in premature infants. WHAT IS KNOWN: • Salivary sampling may be useful when is applied to extremely low birth weight infant, in whom blood sampling must be severely restricted. WHAT IS NEW: • The measurement of caffeine salivary concentrations after intravenous or oral administration offers an alternative to serum caffeine monitoring in apnoea of prematurity. • Salivary sampling may be a valid non-invasive alternative that could be used to individualize and optimize caffeine dose.

Plasma microRNAs as potential biomarkers in early Alzheimer disease expression.

The microRNAs (miRNAs) are potential biomarkers for complex pathologies due to their involvement in the regulation of several pathways. Alzheimer Disease (AD) requires new biomarkers in minimally invasive samples that allow an early diagnosis. The aim of this work is to study miRNAS as potential AD biomarkers and their role in the pathology development. In this study, participants (n = 46) were classified into mild cognitive impairment due to AD (MCI-AD, n = 19), preclinical AD (n = 8) and healthy elderly controls (n = 19), according to CSF biomarkers levels (amyloid ß42, total tau, phosphorylated tau) and neuropsychological assessment. Then, plasma miRNAomic expression profiles were analysed by Next Generation Sequencing. Finally, the selected miRNAs were validated by quantitative PCR (q-PCR). A panel of 11 miRNAs was selected from omics expression analysis, and 8 of them were validated by q-PCR. Individually, they did not show statistically significant differences among participant groups. However, a multivariate model including these 8 miRNAs revealed a potential association with AD for three of them. Specifically, relatively lower expression levels of miR-92a-3p and miR-486-5p are observed in AD patients, and relatively higher levels of miR-29a-3p are observed in AD patients. These biomarkers could be involved in the regulation of pathways such as synaptic transmission, structural functions, cell signalling and metabolism or transcription regulation. Some plasma miRNAs (miRNA-92a-3p, miRNA-486-5p, miRNA-29a-3p) are slightly dysregulated in AD, being potential biomarkers of the pathology. However, more studies with a large sample size should be carried out to verify these results, as well as to further investigate the mechanisms of action of these miRNAs.

Cardiovascular risk assessment with carotid ultrasound in rheumatoid arthritis.

BACKGROUND/OBJECTIVE: To assess the Cardiovascular Risk (CV) in Rheumatoid Arthritis (RA) patients using carotid ultrasound additionally to the traditional CV risk factors. METHODS: A cross-sectional case control study was performed including RA patients and matched controls. This study was performed from July-2019 to January-2020. Population over 75 years old, established CV disease and/or chronic kidney disease (from III Stage) were excluded. Statistical analysis included a multivariate variance analysis (Manova) and a negative binomial regression adjusted by confounding factors. RESULTS: Overall, a total of 200 cases and 111 controls were included in the study. Demographical and clinical variables were comparable between groups. A relationship between age, BMI and high blood pressure was detected in both groups. RA patients showed higher intima-media thickness and higher plaque account compared to controls and it was related to the disease duration and DAS28 score. CONCLUSION: RA leads to a higher intima-media thickness, and this is related to the disease duration and DAS28 score. These findings support that RA acts as an independent cardiovascular risk factor.

Integrating Clinics, Laboratory, and Imaging for the Diagnosis of Common Variable Immunodeficiency-Related Granulomatous-Lymphocytic Interstitial Lung Disease.

Background: Granulomatous-lymphocytic interstitial lung disease (GLILD) is a distinct clinic-radio-pathological interstitial lung disease (ILD) that develops in 9% to 30% of patients with common variable immunodeficiency (CVID). Often related to extrapulmonary dysimmune disorders, it is associated with long-term lung damage and poorer clinical outcomes. The aim of this study was to explore the potential use of the integration between clinical parameters, laboratory variables, and developed CT scan scoring systems to improve the diagnostic accuracy of non-invasive tools. Methods: A retrospective cross-sectional study of 50 CVID patients was conducted in a referral unit of primary immune deficiencies. Clinical variables including demographics and comorbidities; analytical parameters including immunoglobulin levels, lipid metabolism, and lymphocyte subpopulations; and radiological and lung function test parameters were collected. Baumann's GLILD score system was externally validated by two observers in high-resolution CT (HRCT) scans. We developed an exploratory predictive model by elastic net and Bayesian regression, assessed its discriminative capacity, and internally validated it using bootstrap resampling. Results: Lymphadenopathies (adjusted OR 9.42), splenomegaly (adjusted OR 6.25), Baumann's GLILD score (adjusted OR 1.56), and CD8+ cell count (adjusted OR 0.9) were included in the model. The larger range of values of the validated Baumann's GLILD HRCT scoring system gives it greater predictability. Cohen's κ statistic was 0.832 (95% CI 0.70-0.90), showing high concordance between both observers. The combined model showed a very good discrimination capacity with an internally validated area under the curve (AUC) of 0.969. Conclusion: Models integrating clinics, laboratory, and CT scan scoring methods may improve the accuracy of non-invasive diagnosis of GLILD and might even preclude aggressive diagnostic tools such as lung biopsy in selected patients.

High Levels of Cerebrospinal Fluid Kappa Free Light Chains Relate to IgM Intrathecal Synthesis and Might Have Prognostic Implications in Relapsing Multiple Sclerosis.

Cerebrospinal kappa free light chain (KFLC)-index is a marker of intrathecal immunoglobulin synthesis that aids in the diagnosis of multiple sclerosis (MS). However, little evidence exists on its prognostic role. Our aim is to analyze the relationship between KFLC-index and other MS biomarkers and to explore its prognostic role. This is a monocentric observational study in a cohort of 52 people with relapsing MS (pwRMS) performed on prospectively acquired clinical data and with retrospective evaluation of biomarkers. We measured KFLC-index, immunoglobulin intrathecal synthesis, cerebrospinal fluid (CSF) chitinase 3-like 1 (CHI3L1), and neurofilament light protein (NFL) and reviewed MRI to detect leptomeningeal contrast enhancement (LMCE). We compared time to Expanded Disability Status Scale (EDSS) 3 and to initiation of high-efficacy disease-modifying therapies (heDMTs) by multivariate Cox regression analysis. Median KFLC-index correlated with IgG/IgM indexes (p < 0.0001/p < 0.05) and IgG-oligoclonal bands (OCGBs) (p < 0.001). Patients with IgM-oligoclonal bands (OCMBs) had a higher KFLC-index (p = 0.049). KFLC-index was higher in patients with LMCE (p = 0.008) and correlated with CHI3L1 (p = 0.007), but disease activity had no effect on its value. Bivariate and multivariate analyses confirmed KFLC-index > 58 as an independent risk factor for reaching an EDSS of 3 (hazard ratio (HR) = 12.4; 95% CI = 1.1-147; p = 0.047) and for the need of treatment with heDMTs (HR = 3.0; 95% CI = 1.2-7.1; p = 0.0013). To conclude, our data suggest a potential prognostic role of the KFLC-index during the MS course.

Predictors of adverse perinatal outcome up to 34 weeks, a multivariable analysis study.

The objective was to evaluate the best predictors of adverse perinatal outcome (APO) in foetuses examined up to 34 weeks and delivered by spontaneous or induced labour. This was a retrospective study of 129 pregnancies that underwent an ultrasound Doppler examination at 23-34 weeks and entered into labour within 30 days. Cerebroplacental ratio (CPR) and mean uterine artery pulsatility index (mUtA PI) were converted into multiples of the median (MoM) and estimated foetal weight (EFW) into centiles to adjust for gestational age (GA). Sonographic and clinical parameters were evaluated using logistic regression analysis.The multivariable model for the prediction of APO presented a notable accuracy: Detection rate (DR) was 39.5% for a false positive rate (FPR) of 5% and 56.8% for a FPR of 10%, AUC 0.82, p < .0001. Significant predictors were GA, EFW centile, and CPR MoM, but not mUtA PI MoM. Moreover, the type of labour onset did not exert any influence on APO. In conclusion, up to 34 weeks, prediction of APO after spontaneous or induced labour may be done measuring CPR and EFW.IMPACT STATEMENTWhat is already known on this subject? Earlier in pregnancy, foetal growth restriction is caused by placental disease causing progressive hemodynamic changes. These changes have been exhaustively described. Conversely, information about the best predictors of adverse outcome is scarce.What do the results of this study add? The findings of this study show that prior to 34 weeks and up to 1 month before labour, labour outcome might be predicted by gestational age, foetal cerebroplacental ratio (CPR) and estimated foetal weight (EFW).What are the implications of these findings for clinical practice and/or further research? If CPR behaves as a good marker of outcome not only at the end of pregnancy but also earlier in gestation, it might be interrogated along with EFW in foetuses attempting vaginal delivery to determine the risk of adverse outcome.

CT-Guided Needle Biopsy in Vertebral Osteomyelitis: Study of Factors That Could Influence in Culture Yield.

OBJECTIVE: The aim of this study was to analyze which are the main factors that could influence the result of a CT guided biopsy in vertebral osteomyelitis (VO) patients. METHODS: A single center retrospective observational study was performed including adult patients who had been diagnosed with VO and undergone CT guided needle biopsy from January 2010 to January 2020. Demographical features, concurrent diseases, laboratory findings, microbiological diagnosis, radiological data, medical complications, antibiotic exposure were compiled. Multivariate analysis was performed with a logistic regression comparing the patients depending on the culture result. RESULTS: Seventy-seven patients were included in the study. Baseline characteristics were comparable between groups. Sample culture was positive in 43 cases (56%). Microorganism isolated were gram+(72%), gram-(14%), mycobacteria (7%) and fungi (7%). Delay in the procedure, antibiotic exposure and blood culture positivity were also similar among both groups. The biopsy results were not influenced by the CRP value, the presence of fever nor antibiotic exposure. The longer duration of back pain was associated to a lower probability of a positive culture. CONCLUSIONS: In conclusion, our study displays an acceptable reliability of CT guided needle biopsy in VO patients, even in cases under antibiotic treatment. The presence of fever or CRP values did not predict a positive culture. Delay in diagnosis could impact negatively on culture yield.

MicroRNA-185-5p: a marker of brain-sparing in foetuses with late-onset growth restriction.

To compare the expression of microRNA-185-5p (miR-185-5p) in normal foetuses and in foetuses with late-onset growth restriction (FGR) and to determine the factors influencing this expression. In a prospective study, 40 foetuses (22 of them with late-onset FGR and 18 with normal growth) were scanned with Doppler ultrasound after week 35 and followed until birth. Subsequently, blood samples from umbilical cords were collected after delivery to evaluate the expression of miR-185-5p using real-time qPCR. Finally, multivariable regression analysis was applied to determine the clinical and ultrasonographic factors influencing miR-185-5p expression in both normal and late-onset FGR foetuses. In comparison with normal foetuses, late-onset FGR foetuses expressed upregulation of miR-185-5p (2.26 ± 1.30 versus 1.27 ± 1.03 2^-ddCt, P = 0.011). Multivariable regression analysis confirmed that cerebroplacental ratio (P < 0.05) was the only determinant of this overexpression. FGR foetuses overexpress miR-185-5p in relation to brain-sparing. Future studies will be needed to investigate the role of miR-185 in the management of late-onset FGR.

Birth-weight differences at term are explained by placental dysfunction and not by maternal ethnicity. Study in newborns of first generation immigrants.

OBJECTIVE: The aim of the study was to investigate the influence of ethnicity and cerebroplacental ratio (CPR) on the birth weight (BW) of first generation Indo-Pakistan immigrants' newborns. METHODS: This was a retrospective study in a mixed population of 620 term Caucasian and Indo-Pakistan pregnancies, evaluated in two reference hospitals of Spain and Italy. All fetuses underwent a scan and Doppler examination within two weeks of delivery. The influence of fetal gender, ethnicity, GA at delivery, CPR, maternal age, height, weight and parity on BW was evaluated by multivariable regression analysis. RESULTS: Newborns of first generation Indo-Pakistan immigrants were smaller than local Caucasian newborns (mean BW mean= 3048 ± 435 g versus 3269 ± 437 g, p < .001). Multivariable regression analysis demonstrated that all studied parameters, but maternal age and ethnicity, were significantly associated with BW. The most important were GA at delivery (partial R2 = 0.175, p < .001), CPR (partial R2 = 0.032, p < .001), and fetal gender (partial R2 = 0,029, p < .001). CONCLUSIONS: The propensity to a lower BW, explained by placental dysfunction but not by maternal ethnicity is transmitted to newborns of first generation immigrants. Whatever are the factors implied they persist in the new residential setting.

Role of the nigrosome 1 absence as a biomarker in amyotrophic lateral sclerosis.

INTRODUCTION: The absence of nigrosome 1 on brain MRI and the hyperechogenicity of substantia nigra (SNh) by transcranial sonography are two useful biomarkers in the diagnosis of parkinsonisms. We aimed to evaluate the absence of nigrosome 1 in amyotrophic lateral sclerosis (ALS) and to address its meaning. METHODS: 136 ALS patients were recruited, including 16 progressive muscular atrophy (PMA) and 22 primary lateral sclerosis (PLS) patients. The SNh area was measured planimetrically by standard protocols. The nigrosome 1 status was qualitatively assessed by two blind evaluators in susceptibility weight images of 3T MRI. Demographic and clinical data were collected and the C9ORF72 expansion was tested in all patients. RESULTS: Nigrosome 1 was absent in 30% of ALS patients (36% of PLS, 29% of classical ALS and 19% of PMA patients). There was no relationship between radiological and clinical laterality, nor between nigrosome 1 and SNh area. Male sex (OR = 3.63 [1.51, 9.38], p = 0.005) and a higher upper motor neuron (UMN) score (OR = 1.10 [1.02, 1.2], p = 0.022) were independently associated to nigrosome 1 absence, which also was an independent marker of poor survival (HR = 1.79 [1.3, 2.8], p = 0.013). CONCLUSION: In ALS patients, the absence of nigrosome 1 is associated with male sex, UMN impairment and shorter survival. This suggests that constitutional factors and the degree of pyramidal involvement are related to the substantia nigra involvement in ALS. Thus, nigrosome 1 could be a marker of a multisystem degeneration, which in turn associates to poor prognosis.

Attentional engagement and inhibitory control according to positive and negative symptoms in schizophrenia: An emotional antisaccade task.

Despite schizophrenia (SZ) is characterized by a high psychopathological heterogeneity, the underlying psychological mechanisms that result in different clinical profiles are unclear. This study examined the cognitive processing of emotional faces (angry, happy, neutral, and sad) by means of assessing inhibitory control (antisaccade task) and attentional engagement (prosaccade task) with the eye-tracking paradigm. Firstly, two clinical SZ subgroups classified according to the predominance of positive (PSZ; n = 20) or negative symptoms (NSZ; n = 34) and a control group of 32 individuals were compared. Secondly, the association between prosaccade and antisaccade measurements and the severity of positive and negative symptoms were analyzed. The PSZ group showed slower antisaccades when angry faces were displayed, and higher positive symptoms were associated with slower prosaccade latencies to ones. Conversely, the NSZ group made overall slower prosaccades with an emotional advantage for angry faces, and higher negative symptoms were associated with faster antisaccade latencies to ones. Hence, whereas positive SZ profile is related to a lack of attentional engagement and an impaired inhibitory control to threatening information; negative SZ profile is linked to a lack of attentional engagement to faces, mainly with non-threat ones, and with an advantage to ignore distracting threatening stimuli. These findings support affective information-processing theories suggesting a hypersensitivity to threat for positive SZ profiles, and a desensitization to socio-emotional information for negative ones. Consequently, characterizing psychological mechanisms of SZ may allow improving current treatments to threat management when positive symptoms are predominant, or emotion sensitization when negative symptoms prevail.

Epigenomics and Lipidomics Integration in Alzheimer Disease: Pathways Involved in Early Stages.

BACKGROUND: Alzheimer Disease (AD) is the most prevalent dementia. However, the physiopathological mechanisms involved in its development are unclear. In this sense, a multi-omics approach could provide some progress. METHODS: Epigenomic and lipidomic analysis were carried out in plasma samples from patients with mild cognitive impairment (MCI) due to AD (n = 22), and healthy controls (n = 5). Then, omics integration between microRNAs (miRNAs) and lipids was performed by Sparse Partial Least Squares (s-PLS) regression and target genes for the selected miRNAs were identified. RESULTS: 25 miRNAs and 25 lipids with higher loadings in the sPLS regression were selected. Lipids from phosphatidylethanolamines (PE), lysophosphatidylcholines (LPC), ceramides, phosphatidylcholines (PC), triglycerides (TG) and several long chain fatty acids families were identified as differentially expressed in AD. Among them, several fatty acids showed strong positive correlations with miRNAs studied. In fact, these miRNAs regulated genes implied in fatty acids metabolism, as elongation of very long-chain fatty acids (ELOVL), and fatty acid desaturases (FADs). CONCLUSIONS: The lipidomic-epigenomic integration showed that several lipids and miRNAs were differentially expressed in AD, being the fatty acids mechanisms potentially involved in the disease development. However, further work about targeted analysis should be carried out in a larger cohort, in order to validate these preliminary results and study the proposed pathways in detail.

Invasive scedosporiosis in lung transplant recipients: A nine-year retrospective study in a tertiary care hospital.

BACKGROUND: Scedosporium species and Lomentospora prolificans (Sc/Lp) are emerging molds that cause invasive disease associated with a high mortality rate. After Aspergillus, these molds are the second filamentous fungi recovered in lung transplant (LT) recipients. AIMS: Our objective was to evaluate the incidence, risk factors and outcome of Sc/Lp infections in LT recipients at a tertiary care hospital with a national reference LT program. METHODS: A nine-year retrospective study was conducted. RESULTS: During this period, 395 LT were performed. Positive cultures for Sc/Lp were obtained from twenty-one LT recipients. Twelve patients (incidence 3.04%) developed invasive scedosporiosis (IS). In 66.7% of the patients with IS the invasive infection was defined as a breakthrough one. The main sites of infection were lungs and paranasal sinuses. Most of the patients received combination antifungal therapy. The IS crude mortality rate after 30 days was 16.7%, and 33.3% after a year. CONCLUSIONS: Our study highlights improved survival rates associated with combination antifungal therapy in LT recipients and underlines the risk of breakthrough infections in patients with allograft dysfunction on nebulized lipidic amphotericin B prophylaxis. In addition to pretransplant colonization, acute or chronic organ dysfunctions seem to be the main risk factors for IS.

Non-invasive monitoring of saliva can be used to identify oxidative stress biomarkers in preterm and term newborn infants.

AIM: The aim of this study was to appraise the feasibility and reproducibility of applying a validated analytical method to determine salivary oxidative stress biomarkers in newborn infants. METHODS: Prospective observational single-centre study was carried out in level III neonatal intensive care unit. Eligible patients were preterm infants and healthy full-term newborn infants. Salivary samples were analysed in the chromatographic system. RESULTS: A total of 23 premature newborn infants and 13 full-term newborns were included. We analysed salivary levels of oxidative stress biomarkers for 5-F2t isoprostane, 15-E2t isoprostane, prostaglandin E2 and prostaglandin F2α. The multivariate predictive model showed a positive association between female and 5-F2t isoprostonae, and between female sex and prostglandin F2α. In addition, we found a positive association between gestational age and levels of prostaglandin E2 . Furthermore, in the premature group, we found a positive association between the inspired fraction of oxygen and levels of prostaglandin G2 . CONCLUSION: We identified and determined lipid peroxidation biomarkers in term and preterm newborn infants' saliva using specific and validated mass spectrometry technology.