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.

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.

Analysis of gluten immunogenic peptides in feces to assess adherence to the gluten-free diet in pediatric celiac patients.

PURPOSE: In celiac disease (CD) there is a need for precise and non-invasive tools to assess dietary compliance to the gluten-free diet (GFD). Our aim is to evaluate the efficacy of the detection of gluten immunogenic peptides (GIP) in feces, to monitor in real life, the adherence to GFD in pediatric patients with CD. METHODS: A cross-sectional, prospective study was conducted. Fecal samples from CD children were analyzed by a rapid immunochromatographic (IC) test and by an ELISA method, both based on the antigliadin 33-mer monoclonal antibody. RESULTS: Group 1 comprises 43 children on a GFD. According to the food records (FR), 39/43 patients were compliant with the GFD and gluten consumption was recorded in 4. GIP were detected in 15/43 individuals by the ELISA method and also in 7 by IC strips. Group 2: comprise 18 children at CD diagnosis; GIP levels decreased over time (p < 0.001) in a non-linear way (p = 0.028) after starting a GFD and were below the detection limit on the third day in most individuals. CONCLUSION: GIP were detected, both by ELISA and by IC strips, in CD patients on a GFD, in which no consumption of gluten had been registered on the FR, confirming GIP detection to be superior to FR discovering involuntary transgressions. Despite a positive correlation between the amount of gluten intake and the concentration of GIP in feces, the interindividual variations observed suggest gastrointestinal factors influencing GIP recovery need to be further investigated.

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.

Delayed vs Immediate Cord Clamping Changes Oxygen Saturation and Heart Rate Patterns in the First Minutes after Birth.

OBJECTIVE: To build arterial oxygen saturation (SpO2) and heart rate (HR) percentiles for the first 10 minutes after birth in term infants born after an uneventful gestation, vaginal delivery, and delayed cord clamping (DCC) for ≥60 seconds, and to compare our results with previous ones constructed after immediate cord clamping. STUDY DESIGN: Preductal SpO2, HR, and timing of DCC immediately after complete fetal body expulsion were recorded. The pulse-oximeter was adjusted in the right wrist/hand and set at maximal intensity and measurements performed every 2 seconds. RESULTS: A total of 282 term newborn infants were included. The definitive data set comprised of 70 257 SpO2 and 79 746 HR measurements. Median and IQR of SpO2 (%) at 1, 5, and 10 minutes after birth were 77 (68-85), 94 (90-96), and 96 (93-98), respectively. HR (beats per minute) median and IQR at 1, 5, and 10 minutes after birth were 148 (84-170), 155 (143-167), and 151 (142-161), respectively. We found significantly higher SpO2 for the 10th, 50th, and 90th percentiles compared with the previous reference ranges for the first 5 minutes and HR for the first 1-2 minutes after birth. CONCLUSIONS: Spontaneously breathing term newborn infants born by vaginal delivery who underwent DCC ≥60 seconds achieved higher SpO2 and HR in the first 5 minutes after birth compared with term neonates born under the same conditions but with immediate cord clamping. Further studies in neonates undergoing cesarean delivery are under way.

Does Uterine Doppler Add Information to the Cerebroplacental Ratio for the Prediction of Adverse Perinatal Outcome at the End of Pregnancy?

OBJECTIVE: To evaluate whether the addition of the mean uterine arteries pulsatility index (mUtA PI) to the cerebroplacental ratio (CPR) improves its ability to predict adverse perinatal outcome (APO) at the end of pregnancy. METHODS: This was a prospective study of 891 fetuses that underwent an ultrasound examination at 34-41 weeks. The CPR and the mUtA PI were converted into multiples of the median (MoM) and the estimated fetal weight (EFW) into centiles according to local references. APO was defined as a composite of abnormal cardiotocogram, intrapartum pH requiring cesarean section, 5' Apgar score <7, neonatal pH <7.10 and admission to pediatric care units. The accuracies of the different parameters were evaluated alone and in combination with gestational characteristics using univariate and multivariate analyses by means of the Akaike Information Criteria (AIC) and the area under the curve (AUC). Finally, a comparison was similarly performed between the CPR and the cerebro-placental-uterine ratio (CPUR; CPR/mUtA PI) for the prediction of APO. RESULTS: The univariate analysis showed that CPR MoM was the best parameter predicting APO (AIC 615.71, AUC 0.675). The multivariate analysis including clinical data showed that the best prediction was also achieved with the CPR MoM (AIC 599.39, AUC 0.718). Moreover, when EFW centiles were considered, the addition of UtA PI MoM did not improve the prediction already obtained with CPR MoM (AIC 591.36, AUC 0.729 vs. AIC 589.86, AUC 0.731). Finally, the prediction by means of CPUR did not improve that of CPR alone (AIC 623.38, AUC 0.674 vs. AIC 623.27, AUC 0.66). CONCLUSION: The best prediction of APO at the end of pregnancy is obtained with CPR whatever is the combination of parameters. The addition of uterine Doppler to the information yielded by CPR does not result in any prediction improvement.

MicroRNA-148b-3p and MicroRNA-25-3p Are Overexpressed in Fetuses with Late-Onset Fetal Growth Restriction.

OBJECTIVE: It was the aim of this study to describe a micro-RNA (miRNA) profile characteristic of late-onset fetal growth restriction (FGR) and to investigate the pathways involved in their biochemical action. METHODS: In this prospective study, 25 fetuses (16 normal and 9 with FGR [estimated fetal weight <10th centile plus cerebroplacental ratio <0.6765 multiples of the median]) were evaluated with Doppler ultrasound after 36 weeks. Afterwards, for every fetus, plasma from umbilical vein blood was collected at birth, miRNA was extracted, and full miRNA sequencing was performed. Subsequently, comparisons were done in order to obtain those miRNAs that were differentially expressed. RESULTS: The FGR fetuses expressed upregulation of two miRNAs: miR-25-3p and, especially, miR-148b-3p, a miRNA directly involved in Schwann cell migration, neuronal plasticity, and energy metabolism (p = 0.0072, p = 0.0013). CONCLUSIONS: FGR fetuses express a different miRNA profile, which includes overexpression of miR-25-3p and miR-148b-3p. This information might improve our understanding of the pathophysiological processes involved in late-onset FGR. Future validation and feasibility studies will be required to propose miRNAs as a valid tool in the diagnosis and management of FGR.

Comparison of Cerebroplacental Ratio, Intergrowth-21st Standards, Customized Growth, and Local Population References for the Prediction of Fetal Compromise: Which Is the Best Approach?

OBJECTIVE: The aim of this work was to compare the accuracy of the cerebroplacental ratio (CPR), Intergrowth 21st standards (IG21), customized growth (CG), and local population references (LPR) in the prediction of intrapartum fetal compromise (IFC). METHODS: This was a prospective study of 714 fetuses that underwent an ultrasound examination at 34-41 weeks and were delivered within a 2-week interval. The CPR was converted into multiples of the median and the estimated fetal weight (EFW) transformed into CG, IG21, and LPR centiles. IFC was defined as a composite of abnormal cardiotocogram, intrapartum pH requiring cesarean section, 5-min Apgar score, and admission to pediatric care units. The accuracies of the CPR and the EFW centiles for the prediction of IFC were evaluated alone and in combination with other gestational characteristics using univariate and multivariate analysis. RESULTS: Individually, the CPR was the parameter that best predicted the existence of IFC (AUC = 0.66). The multivariate analysis showed that the best prediction was again achieved with the CPR, alone or in combination with any of the EFW centiles (AUC = 0.74). No significant differences were seen between the different centile methods. CONCLUSION: The best prediction of IFC is obtained with CPR. Evaluation of CPR should be encouraged in term and late-preterm fetuses.

[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.

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.

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.

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.

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.

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.

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.

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.

Influential factors on dose by ionic dialysance in daily practice in chronic hemodialysis.

BACKGROUND: The determination of Kt/V by ionic dialysance is a technique that has extended its use in hemodialysis clinics. The clinical guidelines have reflected the need to validate this method as a determinant of the dose of dialysis. OBJECTIVES: Determine in daily practice, the influence of hemodialysis characteristics and medication on Kt/V results by ionic dialysance (Kt/V OCM) and compare them with Kt/V measures by serum urea (Kt/V Daugirdas). DESIGN: Cross-sectional and observational study. PARTICIPANTS: 127 patients on chronic hemodialysis. MEASUREMENTS: Descriptive variables, study variables (Kt/VOCM, Kt/VDaugidas), and the variables that modified the effect (patient temperature, serum sodium, vascular access, recirculation, blood flow, hemodialysis technique, dialyzer, acid concentrate, conductivity, dialyzate flow). RESULTS: The mean of Kt/V Daugirdas was 1.84 and the Kt/VOCM mean 1.65; Pearson's was CC r=0.54; P<0.001 and Lin CCC=0.48. In the linear regression, the variables related to hemodialysis technique showed no statistical association with the measurement obtained by Kt/VOCM. Monosodium phosphate and 20% sodium chloride dispensing were associated with a higher Kt/VOCM. CONCLUSIONS: The different technical aspects noted during HD sessions do not influence Kt/V OCM outcomes. Kt/V determined by ionic dialysance isn't similar to that determined by serum urea. When assessing dialysis doses measured by dialysance, consider that it is not the same as determined with serum urea, but it provides an approximation to estimate dialysis doses in real time. It is necessary to consider if drugs or supplements have been administered that can modify it when interpreting the results.