Assessment of oxidative damage to proteins and DNA in urine of newborn infants by a validated UPLC-MS/MS approach

The assessment of oxidative stress is highly relevant in clinical Perinatology as it is associated to adverse outcomes in newborn infants. This study summarizes results from the validation of an Ultra Performance Liquid Chromatography-tandem Mass Spectrometry (UPLC-MS/MS) method for the simultaneous quantification of the urinary concentrations of a set of endogenous biomarkers, capable to provide a valid snapshot of the oxidative stress status applicable in human clinical trials, especially in the field of Perinatology. The set of analytes included are phenylalanine (Phe), para-tyrosine (p-Tyr), ortho-tyrosine (o-Tyr), meta-tyrosine (m-Tyr), 3-NO2-tyrosine (3NO 2-Tyr), 3-Cl-tyrosine (3Cl-Tyr), 2′-deoxyguanosine (2dG) and 8-hydroxy-2′-deoxyguanosine (8OHdG). Following the FDA-based guidelines, appropriate levels of accuracy and precision, as well as adequate levels of sensitivity with limits of detection (LODs) in the low nanomolar (nmol/L) range were confirmed after method validation. The validity of the proposed UPLC-MS/MS method was assessed by analysing urine samples from a clinical trial in extremely low birth weight (ELBW) infants randomized to be resuscitated with two different initial inspiratory fractions of oxygen

Immunological response against SARS-CoV-2 following full-dose administration of Comirnaty® COVID-19 vaccine in nursing home residents

6 páginas, 2 figuras, 3 tablas. Se puede acceder al texto completo de este artículo desde PubMedCentral: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8490129 . Los datos de investigación utilizados en el mismo, se encuentran disponibles en: https://doi.org/10.1016/j.cmi.2021.09.031.Objectives: The current study was aimed at examining SARS-CoV-2 immune responses following two doses of Comirnaty® COVID-19 vaccine among elderly people in nursing homes. Methods: A prospective cohort study in a representative sample from nursing homes in Valencia (n = 881; males: 271, females 610; median age, 86 years) recruited residents using a random one-stage cluster sampling approach. A lateral flow immunochromatography device (LFIC) (OnSite COVID-19 IgG/IgM Rapid Test; CTK BIOTECH, Poway, CA, USA) was used as the front-line test for detecting SARS-CoV-2-Spike (S)-specific antibodies in whole blood obtained using a fingerstick. Residents returning negative LFIC results underwent venipuncture and testing for presence of SARS-CoV-2-S-reactive antibodies and T cells using the Roche Elecsys® Anti-SARS-CoV-2 S (Roche Diagnostics, Pleasanton, CA, USA), the LIAISON® SARS-CoV-2 TrimericS IgG assay (Diasorin S.p.A, Saluggia, Italy) and by flow cytometry, respectively. Results: The SARS-CoV-2-S antibody detection rate in nursing home residents was 99.6% (283/284) and 98.3% (587/597) for SARS-CoV-2 recovered and naïve residents, respectively, within a median of 99 days (range 17-125 days) after full vaccination. Three out of five residents lacking SARS-CoV-2-S antibodies had detectable S-reactive CD8+ and/or CD4+ T cells. In addition, 50/50 and 40/50 participants with detectable SARS-CoV-2 antibodies also had SARS-CoV-2-S-reactive interferon-γ-producing CD4+ and CD8+ T cells, respectively. Discussion: The Comirnaty® COVID-19 vaccine is highly immunogenic in nursing home residents. Keywords: Comirnaty®COVID-19 vaccine; Nursing home residents; SARS-CoV-2; SARS-CoV-2-S antibodies.Ignacio Torres (Río Hortega Contract; CM20/00090), Eliseo Albert (Juan Rodes Contract; JR20/00011) and Estela Gimenez (Juan Rod es Contract, JR18/00053) hold contracts funded by the Health Institute Carlos III (co-financed by the European Regional Development Fund, ERDF/FEDER).Peer reviewe

Foetal haemoglobin, blood transfusion, and retinopathy of prematurity

Stutchfield et al. have recently demonstrated that low foetal haemoglobin (HbF) levels predict retinopathy of prematurity (ROP) . There is an increasing awareness that red blood cell (RBC) transfusions are independent risk factors for all prematurity-associated diseases (PAD). Since adult haemoglobin (HbA) releases oxygen more efficiently than HbF, autologous cord blood (CB) transfusion has been attempted, with limited results due to the low volume of CB collected. We have shown that allogeneic CB RBC concentrates obtained from healthy full-term babies can fulfil transfusion requirements of preterm neonates (PNs) with gestational age 6430 weeks and/or birth weight 641500 g, in their first 28 days of life. At first transfusion episode, PNs received ABO-Rh(D) matched CB-RBCs if available, or adult RBCs if CB units were not available. At subsequent transfusions, the same regimen was adopted, unless CB-RBCs were unavailable. Overall, 9 patients received CB-RBCs and 11 adult-RBCs; 6 patients (3 in each group) died before ROP assessment. Table 1 illustrates ROP findings in 14 surviving patients. All PNs receiving adult-RBCs developed ROP, while two of six patients in the CB-RBC group did not. Stage 3 ROP was observed in four heavily transfused extremely PNs: three of them were transfused only or mainly with adult-RBCs (patients 8,10 and 14, respectively; Table 1). Transfusions contribute to the overwhelming oxidative burden caused by infections, oxygen therapy and inflammatory diseases in PNs. Unfortunately, to monitor in these patients lipid peroxidation products or other biomarkers of the oxidative stress, requires sophisticated methodologies and exceeding volume of biologic samples. Hence, these investigations are so far confined to the research field. In this regard, the study of Stutchfield et al. suggests that monitoring HbF levels in PNs might be a feasible and reliable tool to figure out to what extent transfusions might favour PAD developmen

Flemón parafaríngeo por cuerpo extraño metálico

Los flemones y abcesos parafaríngeos, comunes en la era preantibiótica, son actualmente una entidad poco frecuente. Es necesario un diagnóstico y actitud terapéutica precoz para impedir acrecentar la morbimortalidad asociada. La mayoría de casos descritos se deben a perforaciones de faringe y esófago o por complicación de infecciones del tracto aerodigestivo superior. en un 15% de los casos nos encontraremos con una fase previa al abceso, denominada celulitis, sin que se haya formado colección purulenta, que puede ser solucionado con tratamiento antibiótico sin precisar drenaje quirúrgico. La paciente que presentamos empezó a referir sintomatología después de veinte años de permanencia de un cuerpo extraño en la mandíbula, correspondiendo al resto de una fresa quirúrgica utilizada en la extracción de un corda

Topiramate pharmacokinetics in neonates undergoing therapeutic hypothermia and proposal of an optimised dosing schedule

The adequate dosing of topiramate in neonates undergoing therapeutic hypothermia has not been established. The aim of this study was to design a dosing schedule capable of providing topiramate serum concentrations within the accepted therapeutic range. Methods Neonates (n = 52) with hypoxic ischaemic encephalopathy and subjected to therapeutic hypothermia were dosed with topiramate, 5 mg/kg on day one and 3 mg/kg on days two to five, to decrease seizure events. A total of 451 topiramate serum concentrations obtained in the patients were used to develop a population pharmacokinetic model using a non-linear mixed-effects modelling approach. Results A one-compartment model with first-order absorption and two different clearance terms, one for the cooling period and another for the post-warming period, were used to describe the concentration-time topiramate data. The probability of no-seizure events could not be related to topiramate concentrations, which was attributed to excessively low topiramate concentrations. A modified dosage schedule was designed with the aim of obtaining more than 90% of patients with topiramate concentrations within the therapeutic range after the first dose. Conclusion The dosage schedule of topiramate in these patients should be modified with the aim of decreasing the frequency of seizure events

Erratum: Changes in Perinatal Care and Outcomes in Newborns at the Limit of Viability in Spain: The EPI-SEN Study

<b><i>Background:</i></b> Advances in perinatal care can influence morbidity and mortality in newborns at the limit of viability. Knowledge of these changes over time may help improve clinical decision making, optimize resource allocation and increase quality of care. <b><i>Objectives:</i></b> To evaluate the influence on morbidity and mortality of changes introduced in the perinatal care of preterm infants (22-26 weeks' gestational age, GA) in Spain between two consecutive periods (2002-2006 and 2007-2011). <b><i>Methods:</i></b> An analysis of prospectively collected data in a national database network (SEN1500) was performed. All live newborn infants of 22-26 weeks' GA born in or transferred to referral centers of the SEN1500 network in the first 28 days of life were included. Perinatal interventions, clinical management, neonatal morbidity, and survival until hospital discharge were retrieved. <b><i>Results:</i></b> A total of 5,470 newborns were included (2,533 and 2,937 in each period, respectively). The major changes introduced during the second period were as follows: (1) lower proportion of extramural births (11.0 vs. 8.9%, p = 0.01), (2) increase in antenatal steroids (69.5 vs. 80.8%, p < 0.001), (3) delivery by C-section (41.8 vs. 48.3%, p < 0.001) and (4) use of CPAP during resuscitation (7.8 vs. 20.7%, p < 0.001). Death in the delivery room decreased from 5.1 to 3.2% (p < 0.001). Survival increased from 49.9 to 57.9% (p < 0.001), and survival without major morbidity increased from 18.1 to 21.2% (p = 0.006). <b><i>Conclusions:</i></b> During the second period, a greater attachment to practices proven to have a beneficial impact on survival and reduction of morbidity in the extremely preterm infant was noted, and survival and survival without major morbidity increased. A more conservative approach was detected for newborns of 22 weeks' GA