Search

Purpose To identify presurgical and surgical factors associated with the development of hypopituitarism and its recovery after endoscopic endonasal transsphenoidal (EET) resection of pituitary adenomas (PAs). Methods Retrospective study of patients with PAs operated by the same neurosurgeon through an EET approach in two Spanish tertiary hospitals in ten years. Results 242 pituitary surgeries performed in 231 patients were analyzed. In the 154 surgeries performed in 146 patients with non-functioning PAs (NFPAs), 46.8% (n = 72) presented presurgical hypopituitarism. After PAs resection, 41 of these (56.9%) normalized pituitary function and 11 of 82 patients with preoperative normal function (13.4%) developed new pituitary deficits. Patients with preoperative visual impairment (OR = 3.9, p = 0.046) and operated in the first four years of the neurosurgeon's learning curve (OR = 5.7, p = 0.016) presented a higher risk of developing postoperative hypopituitarism. Of the 88 surgeries in 85 patients with functioning PAs (FPAs), 23.9% presented presurgical hypopituitarism, and 47.6% of those recovered after surgery. 9% of the cases with preoperative normal function developed new pituitary deficit/s. Diabetic patients presented a higher risk of persistence of hypopituitarism (OR = 10.5, p = 0.024). Patients with presurgical visual impairment (OR = 30.0, p = 0.010) and PAs >3 cm (OR = 14.0, p = 0.027) had higher risk of developing new pituitary deficits. Conclusion Approximately 50% of patients with PAs and preoperative hypopituitarism recover pituitary function after EET surgery. 10% of patients with normal function develop new deficits. Patients with NFPAs with visual involvement and operated in the first four years of neurosurgeon's learning curve, and FPAs patients with presurgical visual impairment and tumor size >3 cm have a higher risk of postoperative hypopituitarism.

Background: There is a gap of knowledge regarding cerebrospinal fluid (CSF) ion concentrations in normal and pathological states, particularly during the neonatal period. We aim to compare CSF ion concentrations in newborns with different causes of neonatal-onset epilepsy (NOE) and acute symptomatic seizures (ASS) and controls, to examine their usefulness for diagnostic purposes. Methods: A descriptive retrospective study was conducted from January 2019 to June 2020 in a tertiary hospital. We analyzed CSF K+, Na+, Cl-, and Ca2+ concentrations in frozen samples from patients with neonatal seizures (NS) secondary to NOE and ASS (neonatal arterial ischemic stroke [NAIS] and hypoxicischemic encephalopathy). As the control group, we selected CSF samples from newborns who had undergone CSF analysis as part of the diagnostic workup and in whom central nervous system infections had been ruled out, without signs of dehydration, gastroenteritis, or history of seizures. Results: Sixty-eight newborns were included, 16 with NOE, 13 with ASS, and 39 without NS (control group). In comparison with the control group, [K+]CSF was lower in patients with KCNQ2-related epilepsy (P = 0.007), other causes of NOE (P = 0.010), and NAIS (P = 0.002). Changes in [Na+]CSF, [Cl-]CSF, and [Ca2+]CSF were less consistent among subgroups. Conclusions: Here we report for the first time ionic imbalances in the CSF of neonates with NOE and NAIS. No differences were observed between newborns with different causes of NS. Further studies should be undertaken to investigate the physiopathology behind these changes and their impact on biological function. (C) 2021 Elsevier Inc. All rights reserved.

Anormalitats congènites; Epidemiologia; Microcefàlia Anomalías congénitas; Epidemiología; Microcefalia Congenital abnormalities; Epidemiology; Microcephaly Objective We sought to describe the prevalence of microcephaly and to compare the different cutoff points established by the Brazilian Ministry of Health at various times during a Zika virus epidemic. As a secondary aim, we investigated the possible etiology of the microcephaly. Method This retrospective study utilized newborn participants in the Zika Cohort Study Jundiaí. Newborns from the Zika Cohort Study Jundiaí with an accurate gestational age determination and complete anthropometric data were analyzed, and microcephaly was diagnosed according to the INTERGROWTH-21st curve. At delivery, fluids were tested for specific antibodies and for viruses. Brain images were evaluated for microcephaly. Receiver Operating Characteristic curves were plotted to define the accuracy of different cutoff points for microcephaly diagnosis. Results Of 462 eligible newborns, 19 (4.1%) were positive for microcephaly. Cutoff points corresponding to the curves of the World Health Organization yielded the best sensitivity and specificity. Three of the microcephaly cases (15.8%) were positive for Zika virus infections; nine (47.4%) had intrauterine growth restriction; one had intrauterine growth restriction and was exposed to Zika virus; three had a genetic syndrome (15.8%); and three had causes that had not been determined (15.8%). Conclusions Microcephaly prevalence was 4.1% in this study. Cutoff values determined by the World Health Organization had the highest sensitivity and specificity in relation to the standard IG curve. The main reason for microcephaly was intrauterine growth restriction. All possible causes of microcephaly must be investigated to allow the best development of an affected baby. This work and this manuscript were supported by the Fundação de Amparo à Pesquisa do Estado de São Paulo (SDP#grant 2016/08578-0), the Brazilian Ministry of Health (SDP#grant 861306/2017 and 861307/2017), and the London School of Hygiene and Tropical Medicine (SDP#grant PC0002/16).

To assess the effect of fluid status at baseline (BL) and at the end of the loading phase (LP) of three different ranibizumab regimens: treat-and-extend (TE), fixed bimonthly (FBM) injections and pro re nata (PRN), in patients with neovascular age-related macular degeneration (nAMD).Post hoc analysis of the In-Eye study (phase IV clinical trial).Patients were randomized 1:1:1 to the three study arms and were treated accordingly. The presence and type of fluid, intraretinal fluid (IRF) or subretinal fluid (SRF) and the anatomical and visual outcomes were analysed.Best-corrected visual acuity (BCVA), the mean change from baseline BCVA (BL BCVA), and the proportion of eyes gaining more than 15 letters or losing more than five letters were analysed. Morphological characteristics including the subtype of choroidal neovascular membrane and the development of atrophy and fibrosis were also evaluated.Patients with SRF at LP had better visual outcomes than patients with IRF. The persistence of SRF did not affect the mean change from BL BCVA among the three treatment regimens. However, in patients with IRF mean change from BL BCVA was significantly lower in the FBM group. The presence of IRF at BL and at the end of the loading phase was associated with the development of fibrosis at the end of the study; this result was contrary to that observed for patients with SRF.While SRF is compatible with good visual and anatomical outcomes, IRF leads to worse results in patients with nAMD; our results suggest that patients with IRF have better outcomes when individualized treatment regimens are used (PRN or TE) in contrast with a FBM regimen.

Atorvastatin is the most prescribed 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitor used to lower cardiovascular risk and constitutes one of the best-selling drugs world-wide. Several physiologically based pharmacokinetic (PBPK) models have been developed to assess its non-straightforward pharmacokinetics (PK) as well as that of its metabolites and have been only applied to assess drug-drug interactions (DDI). Here we present a full PBPK model for atorvastatin and its metabolites able to predict within a 2-fold error their PK after the administration of a solid oral dosage form containing the calcium salt of atorvastatin in single and multiple dosing schedules at 20, 40, and 80 mg and 10 mg dose levels, respectively. Internal validation with data from Phase 1 clinical trials as well as external validation in predicting clinically relevant DDIs consolidated model structure and parameterization. The model has been used to quantitatively assess the drug-gene interaction (DGI) between SLCO1B1 polymorphisms and atorvastatin exposure and revealed that patients with a reduced activity in hepatic uptake of atorvastatin are at increased risk of suffering muscle discomfort because of a 30% lower clearance (p 0.01), leading to a 40% and 33% higher (p 0.05) atorvastatin AUC and C

Introduction: There is a paucity of studies examining temporal trends in the incidence and mortality of moderate-to-severe hypoxic-ischemic encephalopathy (HIE) during the last decade of therapeutic hypothermia (TH). Methods: Multicenter cross-sectional study of all infants ≥35 weeks gestational age diagnosed with moderate-to-severe HIE within 6 h of birth in an extensive region of Spain between 2011 and 2019, in order to detect trend changes over time in the (1) annual incidence, (2) severity of neurological and systemic organ involvement, and (3) neonatal death from HIE. Results: Annual incidence rate of moderate-to-severe HIE was 0.84 (95% confidence interval [CI] 0.7–0.97) per 1,000 births, without trend changes over time (p = 0.8), although the proportion of severe HIE infants showed an average annual decline of 0.86 points (95% CI 0.75–0.98). There were 102 (70%) infants diagnosed with moderate HIE and 44 (30%) with severe HIE. TH was offered to 139/146 (95%) infants. Infants with clinical and/or electrical seizures showed a decreasing trend from 56 to 28% (p = 0.006). Mortality showed a nonstatistically significant decline (p = 0.4), and the severity of systemic damage showed no changes (p = 0.3). Obstetric characteristics remained unchanged, while higher perinatal pH values (p = 0.03) and Apgar scores (p = 0.05), and less need for resuscitation (p = 0.07), were found over time. Conclusion: The annual incidence of moderate-to-severe HIE has stabilized at around 1 per 1,000 births, with a temporal trend toward a decrease in severe HIE infants and a slight decline of mortality. No association was found between temporal trends and changes in perinatal/obstetric characteristics over time.

Cocaine consumption is associated with a variety of clinical manifestations. Though cocaine intranasal inhalation always determines nasal mucosal damages, extensive septum perforations, and midline destructions-known as cocaine-induced midline destructive lesions (CIMDL)-affect only a limited fraction of patients. CIMDL is viewed as a cocaine-associated autoimmune phenomenon in which the presence of atypical anti-neutrophil cytoplasmic antibody (ANCA) promotes and/or defines the disease phenotype. A 51-year-old man presented with an intracranial tumor-like lesion by its space-occupying effect. CT also revealed the destruction of the nasal septum and skull base. A diagnosis of CIMDL was made in light of the patient's history as well as findings of the physical and endoscopic examinations, imaging studies, and laboratory testing. There was no evidence of other pathologies. Histopathological results from cerebral biopsy led us to consider the intracranial pathology as an extension of the CIMDL. CIMDL is the result of a necrotizing inflammatory tissue response triggered by cocaine abuse in a subset of predisposed patients. The reported case is the first CIMDL consistent with brain extension mimicking a tumor-like lesion. While the presence of atypical ANCA seems to promote and/or define the disease phenotype, the specific role of these and other circulating autoantibodies needs further investigation.

Importance COVID-19 is caused by SARS-CoV-2, a betacoronavirus that uses the angiotensin-converting enzyme-related carboxypeptidase (ACE2) receptor to gain entry into cells. ACE2 receptor is widely expressed in multiple organs, including the retina, an extension of the central nervous system. The ACE2 receptor is involved in the diabetic and hypertensive retinopathy. Additionally, coronaviruses cause ocular infections in animals, including retinitis, and optic neuritis. Objective To assess whether there is any retinal disease associated with COVID-19. Design We have evaluated 27 asymptomatic subjects, with retinal fundoscopic, optical coherence tomography (OCT) and OCT angiography fourteen days after hospital discharge due to COVID-19 bilateral pneumonia. Results Cotton wool exudates were evident in six out of 27 patients evaluated, a 22%. Cotton wool exudates are a marker vascular disease severity in other medical context, that is diabetes and hypertension, and are associated with increased risk for acute vascular events. Whether antiaggregation therapy may play a role on fundoscopic-selected patients with COVID-19 requires prospective trials.

Antimicrobial resistance (AMR) is a global concern and controlling its spread is critical for the effectiveness of antibiotics. Members of the genus Salmonella are broadly distributed, and wild boar may play an important role in its circulation between peri-urban areas and the environment, due to its frequent interactions both with livestock or human garbage. As the population of these animals is rising due to management on certain hunting estates or the absence of natural predators, the aim of the present work is to identify the mechanisms of AMR present and/or expressed in Salmonella spp. from wild boar populations and to determine the possible role of management-related factors applied to different game estates located in central Spain. The detection of Salmonella spp. was carried out in 121 dead wild boar from 24 game estates, and antimicrobial resistance traits were determined by antibiotic susceptibility testing and screening for their genetic determinants. The effects of feeding supplementation, the proximity of livestock, the existence of a surrounding fence and the density of wild boar on the AMR of the isolates were evaluated. The predominant subspecies and serovar found were S. enterica subsp. enterica (n = 69) and S. choleraesuis (n = 33), respectively. The other subspecies found were S. enterica subsp. diarizonae, S. enterica subsp. salamae and S. enterica subsp. houtenae. AMR was common among isolates (75.2%) and 15.7% showed multi drug resistance (MDR). Resistance to sulphonamides was the most frequent (85.7%), as well as sul1 which was the AMR determinant most commonly found. Plasmids appeared in 38.8% of the isolates, with IncHI1 being the replicon detected with the highest prevalence. The AMR of the isolates increased when the animals were raised with feeding supplementation and enclosed by fences around the estates.

Purpose: The objectives of this study were the creation and validation of a screening tool for age-related macular degeneration (AMD) for routine assessment by primary care physicians, ophthalmologists, other healthcare professionals, and the general population.Methods: A simple, self-administered questionnaire (Simplified Théa AMD Risk-Assessment Scale [STARS] version 4.0) which included well-established risk factors for AMD, such as family history, smoking, and dietary factors, was administered to patients during ophthalmology visits. A fundus examination was performed to determine presence of large soft drusen, pigmentary abnormalities, or late AMD. Based on data from the questionnaire and the clinical examination, predictive models were developed to estimate probability of the Age-Related Eye Disease Study (AREDS) score (categorized as low risk/high risk). The models were evaluated by area under the receiving operating characteristic curve analysis.Results: A total of 3854 subjects completed the questionnaire and underwent a fundus examination. Early/intermediate and late AMD were detected in 15.9% and 23.8% of the patients, respectively. A predictive model was developed with training, validation, and test datasets. The model in the test set had an area under the curve of 0.745 (95% confidence interval [CI] = 0.705-0.784), a positive predictive value of 0.500 (95% CI = 0.449-0.557), and a negative predictive value of 0.810 (95% CI = 0.770-0.844).Conclusions: The STARS questionnaire version 4.0 and the model identify patients at high risk of developing late AMD.Translational Relevance: The screening instrument described could be useful to evaluate the risk of late AMD in patients >55 years without having an eye examination, which could lead to more timely referrals and encourage lifestyle changes.

[EN] The presence of cyclists on Spanish rural roads is ever increasing and currently frequent, and thus becoming a serious safety concern. In rural environments, the risk of a crash is higher than in rural areas. The main cause is the higher speed of motor vehicles during overtaking manoeuvres. This manoeuvre is especially challenging when cyclists ride in groups as they may change size, length, shape, and speed along their route. These variables and those related to road cross-section can influence driver behaviour when overtaking a group of cyclists. To study this, instrumented bicycles were used to ride along five road segments with different geometric and traffic characteristics. Cyclists rode individually and in groups. Overtaking was evaluated by analysing the lateral distance, the speed, and other characteristics of the manoeuvre. Wider roads presented higher lateral clearances and overtaking speeds. Narrower roads had a high opposing lane invasion but a high level of compliance with the minimum lateral clearance. A higher clearance and lower speed of overtaking vehicles was registered when cyclists rode in line. Compliance with the 1.5 m clearance depended on the group configuration, being higher when cyclists rode in line. However, overtaking cyclists riding two abreast presented more accelerative manoeuvres, especially on narrow roads., This research is part of the research project TRA2016-80897-R, funded by MCIN/AEI/10.13039/501100011033 and the research project SPIP2017-02280, funded by the General Directorate of Traffic of Spain.

The bioequivalence of a new ibuprofen 600-mg film-coated tablet obtained by roller compaction was studied in a crossover study with 22 healthy volunteers. Bioequivalence was analyzed based on (a) the S-enantiomer, (b) the R-enantiomer, and (c) the sum of both enantiomers (representing the results of an achiral assay). The bioequivalence conclusion for ibuprofen products should be based not only on AUC and Cmax but also on tmax since tmax is related to the onset of action. However, it is not possible to ensure if bioequivalence has been demonstrated for tmax as regulators have not defined the acceptance range for the difference between medians of tmax in those cases, where tmax is clinically relevant. In this study, it was possible to conclude bioequivalence for tmax based on S-ibuprofen, though this conclusion might be questioned if the decision is based on R-ibuprofen or the achiral method.

To determine the efficacy and safety of the intratympanic infiltration of infliximab at the hearing threshold of patients in follow-up for refractory immune-mediated hearing loss. 17 patients were collected with relapses, despite maintenance treatment with oral azathioprine associated or not with oral prednisone at low doses (between 5 and 7.5 ml/day) or refractory relapses to previous intratympanic corticoid treatment being 19 affected ears infiltrated. We measured the hearing threshold by Pure-Tone Average (PTA) 500–3000 Hz, 125–8000 Hz and 250–8000 Hz in pre-infiltration (baseline) and follow-up 3 weeks post-infiltration with auditory threshold at frequencies 125–8000 Hz. The average age was 50.68 years (±15.23 years). After the administration of intratympanic infliximab, an improvement of the hearing threshold was showed in the Pure-Tone Average (PTA) calculated at 500–3000 Hz (p = 0.004), 125–8000 Hz (p = 0.001) and 250–8000 Hz (p = 0.006). An immediate improvement in low frequencies also was observed: 125, 250 and 500 Hz (p = 0.009, p = 0.002 and p

The US Food and Drug Administration recommends that if a drug product is intended for use in both sexes, similar proportions should be recruited for bioequivalence (BE) studies. In contrast, in Europe, subjects can belong to either sex. Literature suggesting the existence of sex-by-formulation interaction (S × F) is limited to few studies. To investigate if S × F is observed, this work includes 120 BE studies. Differences larger than 20% between the ratio test/reference of women and men or statistically significant S × F occurred in 25 of 120 studies (20.8%). The prevalence is higher in small studies (36.00% vs. 16.8%). Large differences between the ratios of the sex groups are the tails of the distribution. Two studies were repeated, and the differences between the ratios of the sex groups disappeared. The 90% confidence intervals of S × F did not confirm any relevant S × F. There is no evidence to require studies in both sex groups, combined or separately.

AIMS: Generic products can be regarded as therapeutically equivalent and switchable with the reference product. However, switchability between generics is unknown, as direct comparisons between generics are not performed. The aim of this study was to investigate the bioequivalence between generic clopidogrel products by means of adjusted indirect comparisons (AICs). METHODS: AICs were conducted to assess bioequivalence between 4 generic clopidogrel products that are authorised in Serbia. Generics are considered equivalent to the reference if the 90% confidence intervals (CIs) for the ratios test/reference of the maximum concentration (C(max)) and area under the curve up to the last measurable concentration (AUC(0–t)) fall within the acceptance range 80.00–125.00%. However, for AICs between generics, the Canadian acceptance criterion for C(max) was employed, where only the point estimate of C(max) needs to be within 80.00–125.00%. RESULTS: The 90% CIs of the AICs demonstrated bioequivalence within 80.00–125.00% for all AUC(0–t) comparisons. The point estimates of C(max) in all AICs were also within this range. CONCLUSION: This study demonstrates that the bioavailability of these 4 generic clopidogrel products authorised in Serbia is very similar. Despite the limited power of AICs, bioequivalence was demonstrated for all 90% CIs of AUC(0–t) and all 90% CIs of C(max) comparisons were within or very close to the acceptance range, being able to comply with the acceptance criterion employed in Canada for C(max). Therefore, these 4 generic clopidogrel products authorised in Serbia can be considered switchable with each other in clinical practice based on the adjusted indirect comparisons.

The importance of wild boars as game species in Spain is well known. Their feeding habits and intrusive behaviour, together with a progressively wider spreading of populations, increases the interactions of these animals with livestock and humans. Considering that wild boars could have a potential role in the transmission of certain pathogens as salmonellae, the aims of this study were to determine the prevalence of Salmonella spp. in wild boars hunted in central-western Spain, the occurrence of this pathogen in tonsils, mandibular lymph nodes and faeces (as markers for transmission risk), and to define the phylogenetic relationships among isolated strains, in order to investigate the circulation pathways of bacteria among tissues, animals and estates. Samples from 1,041 hunted wild boars were analysed for the presence of Salmonella spp. by bacteriological culture. Isolates were confirmed by PCR and serotyped in the Spanish national reference laboratory. The genetic relationships between strains were determined by PFGE. The results showed a 7.7% of positive animals (81 wild boars), being tonsils the organ most frequently colonised by Salmonella spp. (18.7%), followed by lymph nodes (5.1%) and faecal samples (2.9%). Serovars Enteritidis and Newport were the most frequent amongst the 34 different serovars obtained. The pulsed-field gel electrophoresis (PGFE) analysis showed a great genetic diversity, with serovars that exhibited different pulsotypes when isolated from different estates and multiple serovars in the same estate. In conclusion, this study reveals the importance of wild boars as carriers and possible transmitters of virulent and/or antimicrobial-resistant clones of Salmonella spp. to livestock and humans.

Magnetic resonance imaging is the gold standard technique in establishing the diagnosis of neonatal arterial ischemic stroke (NAIS). The diagnostic value of cranial ultrasound scanning in this clinical context is controversial. We aimed to assess the current sensitivity of the cranial ultrasound scan (CUS) in detecting NAIS, as this issue has not been well described in the literature. Newborns with NAIS diagnosed by magnetic resonance imaging between 2010 and 2016 were included. All CUSs were blindly analyzed retrospectively by a neonatologist expert in neuroimaging and compared with the findings of non-expert evaluators recorded on medical charts immediately after performing the evaluation. The overall sensitivity of CUS in detecting an imaging finding suggestive of NAIS was 87% (95% confidence interval (CI): 79%-95%) for an expert evaluator, but declined to 72% (61%-83%) when performed by a non-expert evaluator (p 0.002). Sensitivity was 83% and 61% in the first 24 h and 86% and 66% at 24-48 h for expert and non-expert evaluators, respectively (p < 0.05). CUS has higher sensitivity than previously reported in the detection of a NAIS, for both expert and non-expert evaluators. These findings may be explained by the advanced technology of new ultrasound equipment. Expertise in performing CUS is useful, particularly in the first 48 h after clinical debut.

Therapeutic hypothermia (TH) has been the standard treatment for neonatal Hypoxic-Ischemic En cephalopathy (HIE) for more than a decade. This therapy has been one of the best studied treatments in neonatal medicine, moving from preclinical models to patient application. Its implementation has been accompanied by the development of neuromonitoring, neonatal neurology as a specific area of expertise, and the intense search for new neuroprotective strategies. This article provides an update on the clinical scope of this therapy, with emphasis on the problems of our geographic region. In addition, some additional strategies that can improve the therapeutic efficacy of TH are reviewed, as well as controversial aspects in its application and some future perspectives in the care of neonates with HIE.

To assess the effect of clinical factors on the development and progression of atrophy and fibrosis in patients with neovascular age-related macular degeneration (nAMD) receiving long-term treatment in the real world.An ambispective 36-month multicentre study, involving 359 nAMD patients from 17 Spanish hospitals treated according to the Spanish Vitreoretinal Society guidelines, was designed. The influence of demographic and clinical factors, including the presence and location of retinal fluid, on best-corrected visual acuity (BCVA) and progression to atrophy and/or fibrosis were analysed.After 36 months of follow-up and an average of 13.8 anti-VEGF intravitreal injections, the average BCVA gain was +1.5 letters, and atrophy and/or fibrosis were present in 54.8% of nAMD patients (OR = 8.54, 95% CI = 5.85-12.47, compared to baseline). Atrophy was associated with basal intraretinal fluid (IRF) (OR = 1.87, 95% CI = 1.09-3.20), whereas basal subretinal fluid (SRF) was associated with a lower rate of atrophy (OR = 0.40, 95% CI = 0.23-0.71) and its progression (OR = 0.44, 95% CI = 0.26-0.75), leading to a slow progression rate (OR = 0.34, 95% CI = 0.14-0.83). Fibrosis development and progression were related to IRF at any visit (p 0.001). In contrast, 36-month SRF was related to a lower rate of fibrosis (OR = 0.49, 95% CI = 0.29-0.81) and its progression (OR = 0.50, 95% CI = 0.31-0.81).Atrophy and/or fibrosis were present in 1 of 2 nAMD patients treated for 3 years. Both, especially fibrosis, lead to vision loss. Subretinal fluid (SRF) was associated with good visual outcomes and lower rates of atrophy and fibrosis, whereas IRF yields worse visual results and a higher risk of atrophy and especially fibrosis in routine clinical practice.

Road cycling, both individually and in groups, is common in Spain, where most two-lane rural roads have no cycle lanes. Due to this, and the difference in speed between drivers and cyclists, the overtaking manoeuvre is one of the most dangerous interactions. This study analyses how road geometry influences the overtaking manoeuvre performance. Field data of 1355 overtaking manoeuvres were collected using instrumented bicycles, riding along different rural road segments, and considering individual, medium and large groups of cyclists. The safety variables that characterise the overtaking manoeuvre are overtaking vehicle speed and lateral clearance. These variables have been correlated to geometric characteristics of the road, such as the type of centre line, the horizontal alignment, the speed limit, and the road cross section. Regression models have been fitted considering each cyclist group size and configuration. For individuals and medium groups, wider roads generate higher lateral clearances and lower overtaking speeds, while for large groups only the solid centre line was significant, generating lower clearances and higher speeds. Results suggest that other factors need to be considered, especially for large groups. Results offer a deeper understanding of the phenomenon by providing key points for improving road geometry design, such as widening the shoulders.

Age-related macular degeneration (AMD) is a multifactorial disease of the retina featured by dysfunction of retinal pigmented epithelial (RPE) and loss of photoreceptor cells under oxidative stress and inflammatory conditions. Vitamin D and antioxidants have beneficial effects against retinal degenerative diseases, such as AMD. We investigated the impact of associating vitamin D (ND) with a nutritional antioxidant complex (Nutrof Total®, N) on oxidative stress and inflammation-like induced conditions by H2O2 and LPS, respectively, in human retinal epithelial (ARPE-19) and human retinal endothelial (HREC) cells. Application of either N or ND treatments to H2O2-induced media in ARPE-19 cells counteracted late apoptosis, attenuated oxidative DNA damage, and increased cell proliferation. Significant reduction in the expression levels of MCP1, IL-8, and IL6 cytokines was observed following application of either N or ND treatments under LPS-induced conditions in ARPE-19 cells and in MCP-1 and IL12p70 cytokine levels in HREC cells. ND and not N revealed significant downregulation of IFNγ in ARPE-19 cells, and of IL-6 and IL-18 in HREC cells. In conclusion, adding vitamin D to Nutrof Total® protects in a synergistic way against oxidative and inflammatory stress-induced conditions in retinal epithelial and endothelial cells.

Diabetic neuropathy represents a polyneuropathy with electrophiosiological alterations. Electroneuromyography (NMD) plays an important role in the evaluation of patient with diabetes mellitus type 2 (DM2) and doubtful neuropathy.To determine clinical manifestations in patients with distal symmetrical sensory polyneuropathy (DSSP) and to correlate them with electromyographic alterations.Transversal, analytical study. 138 patients over 18 years old, with DM2 and PSSD were selected. They underwent physical examination, laboratory studies and electromyography (EM) with 4-channel Nicolet electromyograph. Measures of central tendency and their dispersion were analyzed; data normality with Kolmogorov-Smirnov; Student's t test and Spearman's correlation.Thalar hyperkeratosis was the most frequent clinical finding in 103 (74%) patients. The most frequent symptoms were paresthesia in 132 (95.7%) patients and tingling in 93 (67.4%) patients. Exploration of superficial sensitivity determined neuropathy in 42 (30.4%) patients finding greater insensitivity in the medial plantar nerve territory. In the EM, the nerve with the greatest absent response was the left lateral plantar nerve in 51 (59%) patients. A significant correlation (p0.05) was found between the variables of EM with age, years of evolution and levels of glycated hemoglobin A1c.The higher the lack of glycemic control, the chronobiology of the patient and the time of illness, the greater the electromyographic affection.la neuropatía diabética representa una polineuropatía con alteración electrofiosiológica. La electroneuromiografía (ENM) desempeña un papel importante en la evaluación del paciente con diabetes mellitus tipo 2 (DM2) y neuropatía dudosa.determinar las manifestaciones clínicas en pacientes con polineuropatía sensitiva simétrica distal (PSSD) y correlacionarlas con alteraciones electroneuromiográficas.estudio transversal, analítico. Se seleccionaron 138 pacientes mayores de 18 años, con DM2 y PSSD. Se les realizó exploración física, estudios de laboratorio y ENM con electromiógrafo Nicolet de 4 canales. Se analizaron las medidas de tendencia central y su dispersión; normalidad de datos con Kolmogorov-Smirnov; t de Student y correlación de Spearman.la hiperqueratosis talar fue el hallazgo clínico más frecuente en 74% de los pacientes. Los síntomas más frecuentes fueron parestesias en 95.7% y hormigueo en 67.4%. La exploración de sensibilidad superficial determinó neuropatía en 30.4%, encontrando mayor insensibilidad en el territorio del nervio plantar medial. En la ENM, el nervio con mayor respuesta ausente fue el plantar lateral izquierdo en 59%. Se encontró correlación significativa (p0.05) entre las variables electroneuromiograficas con la edad, años de evolución y niveles de hemoglobina glucosilada A1c (HbA1c).a mayor descontrol glucémico, cronobiología del paciente y tiempo del padecimiento, mayor es la afección electroneuromiográfica.

Serious intraocular toxicity cases have been reported worldwide after the use of different perfluorocarbon liquids. The current study reports for the first-time the clinical pictures of cases of acute intraocular toxicity caused by MEROCTANE, a perfluoro-octane commercialized by a Turkish company and distributed in many countries. A series of 18 cases from Chile and Spain was retrospectively analysed. To evaluate the impurity profile, a suspicious MEROCTANE sample (lot OCT.01.2013) was analysed by gas chromatography mass spectrometry and compared with a non-suspicious sample of the same commercial perfluoro-octane (lot OCT 722011). Cytotoxicity was tested following a direct-contact method, taking into consideration the high volatility and hydrophobicity of perfluoro-octane and following the ISO 10993 guideline. Cytotoxicity test showed clear cytotoxic effects of the analysed batch (less than 9% of cell viability). Moreover, chemical analysis demonstrated the presence of many contaminants, some highly toxic (acids and alcohols). Perfluorocarbon liquids are useful tools for intraocular surgery but companies and Agencies of Medical Devices must implement measures that guarantee the safety of these products based on both chemical and cytotoxicity analysis for every batch. Medical staff should be encouraged to report any suspected case to their respective National Agencies.

Background: Myopia is a highly prevalent disorder, and one of the first causes of blindness. In turn, alcohol consumption has been shown to be a risk factor for many diseases and a main contributor to the global burden of disease. However, no studies have investigated the relationship between alcohol intake and myopia. Our aim was to prospectively assess the association between alcohol intake and the development or progression of myopia. Methods: In a Spanish dynamic prospective cohort (the SUN Project) we assessed 15,642 university graduates, recruited between 1999 and 2018 and followed up biennially through mailed questionnaires. Alcohol intake was assessed with a validated 136-item food frequency questionnaire. Development or progression of myopia was collected in subsequent questionnaires during follow-up every two years. Results: Alcohol intake was linearly and significantly associated with a higher risk of myopia development or progression: the OR for 10-year incidence/progression of myopia was 1.05, 95% CI 1.01–1.09 per each 10-grams increase in alcohol intake. Conclusions: Alcohol consumption might lead to the development or progression of myopia, although confir- mation is needed for the mechanisms through which this association may occur, thus further research is needed to verify these findings

ObjectiveIn contrast to motor impairments, the association between lesion location and cognitive or language deficits in patients with neonatal arterial ischaemic stroke remains largely unknown. We conducted a voxel-based lesion-symptom mapping cross-sectional study aiming to reveal neonatal arterial stroke location correlates of language, motor and cognitive outcomes at 2 years of age.DesignProspective observational multicentre study.SettingSix paediatric university hospitals in Spain.ParticipantsWe included 53 patients who had a neonatal arterial ischaemic stroke with neonatal MRI and who were followed up till 2 years of age.Main outcome measuresWe analysed five dichotomous clinical variables: speech therapy (defined as the need for speech therapy as established by therapists), gross motor function impairment, and the language, motor and cognitive Bayley scales. All the analyses were controlled for total lesion volume.ResultsWe found that three of the clinical variables analysed significantly correlated with neonatal stroke location. Speech therapy was associated with lesions located mainly at the left supramarginal gyrus (p=0.007), gross motor function impairment correlated with lesions at the left external capsule (p=0.044) and cognitive impairment was associated with frontal lesions, particularly located at the left inferior and middle frontal gyri (p=0.012).ConclusionsThe identification of these susceptible brain areas will allow for more precise prediction of neurological impairments on the basis of neonatal brain MRI.

Although knowledge of the bioactive compounds produced by species inhabiting coastal waters is increasing, little is known about the bioactive potential produced by marine species occupying deeper habitats with high biodiversity and productivity. Here, we investigate about the bioactive potential of molecules produced by species that inhabit the crinoid beds, a poorly known essential fish habitat affected by trawling, wherein large amounts of commercial and noncommercial species are discarded. Based on a trawl survey conducted in 2019, 14% of the 64 species discarded on crinoid beds produce molecules with some type of bioactive potential, including, soft corals (Alcyonium palmatum), tunicates (Ascidia mentula), bony fish, such as horse mackerel (Trachurus trachurus), European hake (Merluccius merluccius), and chondrichthyans, such as small-spotted catshark (Scyliorhinus canicula). In addition, 16% of the discarded species had congeneric species that produce compounds with bioactive potential, indicating that such species might also possess similar types of bioactive molecules. Molecules with antioxidant, antitumour, antihypertensive, and antibacterial properties were the most frequent, which could provide the basis for future research aiming to discover new marine-based drugs and compounds for other human uses. Among all species or genera that produce compounds with bioactive potential, 68% presented medium or high vulnerability to trawling. Results show that the discarded catch contains many species, which produce different bioactive compounds that represent an added-value resource. These results highlight the importance of manage properly crinoid beds, to ensure that species that produce molecules with bioactive potential inhabiting these habitats are protected.

The purpose of this study is evaluate the efficacy and safety of medicinal products containing the original Age-Related Eye Disease group (AREDS) formulation at doses approved in Europe (EU, control group, n = 59) with a product that adds DHA, lutein, zeaxanthin, resveratrol and hydroxytyrosol to the formula (intervention group, n = 50). This was a multicenter, randomized, observer-blinded trial conducted in patients aged 50 years or older diagnosed with unilateral exudative Age related Macular Degeneration AMD. At month 12, the intervention did not have a significant differential effect on visual acuity compared with the control group, with an estimated treatment difference in Early Treatment Diabetic Retinopathy Study (ETDRS) of −1.63 (95% CI −0.83 to 4.09, p = 0.192). The intervention exhibited a significant and, in most cases, relevant effect in terms of a reduction in some inflammatory cytokines and a greater improvement in the fatty acid profile and serum lutein and zeaxantin concentration. In patients with unilateral wet AMD, the addition of lutein, zeaxanthin, resveratrol, hydroxytyrosol and DHA to the AREDS EU recommended doses in the short-term did not have a differential effect on visual acuity compared to a standard AREDS EU formula but, in addition to improving the fatty acid profile and increasing carotenoid serum levels, may provide a beneficial effect in improving the proinflammatory and proangiogenic profile of patients with AMD.

Background: Mitochondrial DNA (mtDNA) diseases are a group of maternally inherited genetic disorders caused by a lack of energy production. Currently, mtDNA diseases have a poor prognosis and no known cure. The chance to have unaffected offspring with a genetic link is important for the affected families, and mitochondrial replacement techniques (MRTs) allow them to do so. MRTs consist of transferring the nuclear DNA from an oocyte with pathogenic mtDNA to an enucleated donor oocyte without pathogenic mtDNA. This paper aims to determine the efficacy, associated risks, and main ethical and legal issues related to MRTs. Methods: A bibliographic review was performed on the MEDLINE and Web of Science databases, along with searches for related clinical trials and news. Results: A total of 48 publications were included for review. Five MRT procedures were identified and their efficacy was compared. Three main risks associated with MRTs were discussed, and the ethical views and legal position of MRTs were reviewed. Conclusions: MRTs are an effective approach to minimizing the risk of transmitting mtDNA diseases, but they do not remove it entirely. Global legal regulation of MRTs is required.

To develop and test the Neonatal Encephalopathy-Rating Scale (NE-RS), a new rating scale to grade the severity of neonatal encephalopathy (NE) within the first 6 hours after birth.A 3-phase process was conducted: (1) design of a comprehensive scale that would be specific, sensitive, brief, and unsophisticated; (2) evaluation in a cohort of infants with neonatal encephalopathy and healthy controls; and (3) validation with brain magnetic resonance imaging findings and outcome at 2 years of age.We evaluated the NE-RS in 54 infants with NE and 28 healthy infants. The NE-RS had excellent internal consistency (Cronbach alpha coefficient: 0.93 [95% CI 0.86-0.94]) and reliability (intraclass correlation coefficient in the NE cohort 0.996 [95% CI 0.993-0.998; P .001]). Alertness, posture, motor response, and spontaneous activity were the top discriminators for degrees of NE. The cut-off value for mild vs moderate NE was 8 points (area under the curve [AUC] 0.99, 95% CI 0.85-1.00) and for moderate vs severe NE, 30 points (AUC 0.93, 95% CI 0.81-0.99). The NE-RS was significantly correlated with the magnetic resonance imaging score (Spearman Rho 0.77, P .001) and discriminated infants who had an adverse outcome (AUC 0.91, 95% CI 0.83-0.99, sensitivity 0.82, specificity 0.81, positive predictive value 0.87, negative predictive value 0.74).The NE-RS is reliable and performs well in reflecting the severity of NE within the first 6 hours after birth. This tool could be useful when assessing clinical criteria for therapeutic hypothermia in NE.

The novel semi-autonomous vehicles are becoming a reality in our roads, being a very important technological advance with promising operational and safety improvements. However, road infrastructure must be ready to host them. The technologies of these driving automation systems require certain road conditions that are not always fulfilled, causing the systems to fail. These failures generally transfer negotiation control to drivers, which may induce a crash if they were not aware of road and traffic conditions. This research analyses how ready the road horizontal alignment is for existing semi-autonomous systems. A Level 2 vehicle has been tested on many different horizontal curves, finding a strong relationship between the maximum speed that the autonomous system can attain and the curve geometry. This maximum speed is proposed as a new concept (automated speed) and has been found to be lower than the design, operating and posted speeds in many cases. Another new concept – automated driving consistency – arises, as the difference between automated and operating speeds. The related inconsistencies can be addressed with the new concept of Level of Service for Automated Driving (LOSAD), which summarizes how ready a corridor is for a certain driving automation system. This parameter should be determined – further certified – for any homogeneous road segment, and later informed to drivers.

One possible application of Near Infrared techniques is to analyze human brain metabolic activity. Currently used models take into account the layered structure of the human head but, usually, they do not consider the non-planar surface of some of the boundaries, i.e. gray matter, which results in a much more complex structure, thus leading to more sophisticated models and longer calculation times. The main objective of this work is to determine if it is worth to replace a planar layered structure by a non-planar one. To this end we implement a Bayesian-based quantitative methodology for choosing between two competitive models describing light propagation in layered turbid media. Experiments of time-resolved diffuse reflectance measurements are performed in layered phantoms and complemented with numerical calculations. The resulting Distributions of Time of Flight of both models are compared using Bayesian model selection analysis. The non-planar interface was introduced in the simulations by a simple surface parametrization. Results suggest that, under certain conditions, a multilayer model with planar boundaries is good enough. Fil: Vera, Demián Augusto. Universidad Nacional del Centro de la Provincia de Buenos Aires. Centro de Investigaciones en Física e Ingeniería del Centro de la Provincia de Buenos Aires. - Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Tandil. Centro de Investigaciones en Física e Ingeniería del Centro de la Provincia de Buenos Aires. - Provincia de Buenos Aires. Gobernación. Comisión de Investigaciones Científicas. Centro de Investigaciones en Física e Ingeniería del Centro de la Provincia de Buenos Aires; Argentina Fil: Baez, Guido Rodrigo. Universidad Nacional del Centro de la Provincia de Buenos Aires. Facultad de Ciencias Exactas. Grupo de Plasmas Densos Magnetizados. Provincia de Buenos Aires. Gobernación. Comisión de Investigaciones Científicas. Grupo de Plasmas Densos Magnetizados; Argentina. Universidad Nacional del Centro de la Provincia de Buenos Aires. Centro de Investigaciones en Física e Ingeniería del Centro de la Provincia de Buenos Aires. - Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Tandil. Centro de Investigaciones en Física e Ingeniería del Centro de la Provincia de Buenos Aires. - Provincia de Buenos Aires. Gobernación. Comisión de Investigaciones Científicas. Centro de Investigaciones en Física e Ingeniería del Centro de la Provincia de Buenos Aires; Argentina Fil: García, Héctor Alfredo. Universidad Nacional del Centro de la Provincia de Buenos Aires. Centro de Investigaciones en Física e Ingeniería del Centro de la Provincia de Buenos Aires. - Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Tandil. Centro de Investigaciones en Física e Ingeniería del Centro de la Provincia de Buenos Aires. - Provincia de Buenos Aires. Gobernación. Comisión de Investigaciones Científicas. Centro de Investigaciones en Física e Ingeniería del Centro de la Provincia de Buenos Aires; Argentina Fil: Iriarte, Daniela Ines. Universidad Nacional del Centro de la Provincia de Buenos Aires. Centro de Investigaciones en Física e Ingeniería del Centro de la Provincia de Buenos Aires. - Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Tandil. Centro de Investigaciones en Física e Ingeniería del Centro de la Provincia de Buenos Aires. - Provincia de Buenos Aires. Gobernación. Comisión de Investigaciones Científicas. Centro de Investigaciones en Física e Ingeniería del Centro de la Provincia de Buenos Aires; Argentina Fil: Pomarico, Juan Antonio. Universidad Nacional del Centro de la Provincia de Buenos Aires. Centro de Investigaciones en Física e Ingeniería del Centro de la Provincia de Buenos Aires. - Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Tandil. Centro de Investigaciones en Física e Ingeniería del Centro de la Provincia de Buenos Aires. - Provincia de Buenos Aires. Gobernación. Comisión de Investigaciones Científicas. Centro de Investigaciones en Física e Ingeniería del Centro de la Provincia de Buenos Aires; Argentina

Introduction Hypoxic ischemic encephalopathy is a neurological condition occurring immediately after birth following a perinatal asphytic episode. Therapeutic hypothermia is a safe and effective intervention to reduce mortality and major disability in survivors. In Latin America, perinatal asphyxia is a major problem, but no data are available characterizing its current situation in the region or the impact of hypoxic ischemic encephalopathy on its management. Objective Understand the prevalence, mortality and use of therapeutic hypothermia in newborns at ≥36 weeks gestational age with hypoxic ischemic encephalopathy admitted to neonatal units reporting to the Ibero-American Society of Neonatology Network. Methods The Ibero-American Society of Neonatology Network groups various neonatology centers in Latin America that share information and collaborate on research and medical care. We evaluated data on newborns with ≥36 weeks gestational age reported during 2019. Each unit received a guide with definitions and questions based on the Society's 7th Clinical Consensus. Evaluated were encephalopathy frequency and severity, Apgar score, need for resuscitation at birth, use of therapeutic hypothermia and clinical evolution at discharge. Our analysis includes descriptive statistics and comparisons made using the chi-square test. Results We examined reports of 2876 newborns from 33 units and 6 countries. In 2849 newborns with available data, hypoxic encephalopathy prevalence was 5.1% (146 newborns): 27 (19%) mild, 36 (25%) moderate, 43 (29%) severe, and 40 (27%) of unknown intensity. In those with moderate and severe encephalopathy, frequencies of Apgar scores ≤3 at the first minute (p = 0.001), Apgar scores ≤3 at the fifth minute (p ⟨0.001) and advanced resuscitation (p = 0.007) were higher. Therapeutic hypothermia was performed in only 13% of newborns (19). Neonatal mortality from encephalopathy was 42% (61). Conclusions Hypoxic ischemic encephalopathy is a neonatal condition that results in high mortality and severe neurological sequelae. In this study, the overall prevalence was 5.1% with a mortality rate of 42%. Although encephalopathy was moderate or severe in 54% of reported cases, treatment with hypothermia was not performed in 87% of newborns. These data reflect a regional situation that requires urgent action.

Objective: To know the distribution of births of very low birth weight infants by day of the week, and whether this distribution affects the morbidity and mortality in this group of patients. Methods: This was a retrospective analysis of data collected prospectively in the Spanish SEN1500 network (2002–2011). Outborn infants, patients with major congenital anomalies, and those who died in the delivery room were excluded. Births were grouped into “weekdays” and “weekends.” A multivariate logistic regression analysis was conducted to evaluate the independent effect of the birth moment on outcomes, and Cox regression for survival. Results: Out of a total of 27,205 very low birth weight infants born at and/or admitted to the participating centers, 22,961 (84.4%) met inclusion criteria. A reduction of 24% in the number of births was observed during the “weekends” compared with “weekdays”. In the raw analysis, patients born on weekends exhibited higher morbidity and mortality (mortality rate: 14.2% vs. 16.5%, p

High myopia and the subsequent degenerative changes of the retina, choroid, and sclera, known as myopic maculopathy (MM), are a serious visual problem in many Asian countries, and are beginning to be so in the south of Europe, especially in the Mediterranean. It is therefore necessary to carry out genetic and environmental studies to determine the possible causes of this disease. This study aims to verify if the genetic factors that have been most related to Asian populations are also associated in two Spanish cohorts. Eight SNPs from six genes (PAX6, SCO2, CCDC102B, BLID, chromosome 15q14, and COL8A1) along with demographic, ophthalmic and environmental factors were analysed in two cohorts from a total of 365 highly myopic subjects and 177 control subjects. The genetic analysis showed that COL8A1 SNP rs13095226 was associated with the development of choroidal neovascularization (CNV) and also seems to play an important role in the increase of axial length. The SNP rs634990 of chromosome 15q14 also showed a significant association with MM, although this was lost after the Bonferroni correction. Additional demographic and environmental factors, namely age, sex, smoking status, and pregnancy history, were also found to be associated with MM and CNV in this population.

Introduction: There are no data on the incidence of hypoxic-ischaemic encephalopathy (HIE) and the implementation of therapeutic hypothermia (TH) in Spain. Methods: This is a cross-sectional, national study, performed using an on-line questionnaire targeting level III neonatal care units in Spain. Participants were requested to provide data of all newborns ≥ 35 weeks of gestational age diagnosed with moderate-severe HIE over a two year-period (2012–2013), and of the implementation of TH up to June 2015. Results: All (90) contacted hospitals participated. HIE incidence rate was 0.77/1000 live newborns (95% CI 0.72–0.83). During 2012–2013, 86% of the newborns diagnosed with moderate-severe HIE received TH (active or passive). Active TH was increasingly used, from 78% in 2012 to 85% in 2013 (P = .01). Of the 14% that did not receive TH, it was mainly due to a delay in the diagnosis or inter-hospital transfer, and to the fact that the treatment was not offered. More than half (57%) were born in hospitals where TH was not provided, and passive hypothermia was used for inter-hospital patient transfer, and in 39% of the cases by inappropriately trained personnel. By June 2015, 57 out of 90 centres had implemented TH, of which 54 performed whole-body TH (using servo-controlled devices). The geographical distribution of centres with active TH, and the number of newborn that received TH, was heterogeneous. Conclusions: The incidence of moderate-severe HIE is homogeneous across Spanish territory. Significant progress is being made in the implementation of TH, however it is necessary to increase the availability of active TH between Autonomous Communities, to improve early diagnosis, and to guarantee high quality patient transfer to referral centres. Resumen: Introducción: La incidencia de la encefalopatía hipóxico-isquémica perinatal (EHI) y la implementación de la hipotermia terapéutica (HT) es desconocida en España. Método: Estudio transversal nacional en recién nacidos vivos (RNV) ≥ 35 semanas de gestación mediante cuestionario on-line en las 90 unidades neonatales de nivel iii. Se solicitaron datos de los RNV con EHI moderada-grave en los años 2012 y 2013, y de la implementación de la HT en junio del 2015. Resultados: Se recibieron datos de los 90 hospitales. La incidencia de EHI moderada-grave fue 0.77/1.000 RNV (IC del 95%, 0.72; 0.83). El 86% de los RNV con EHI recibieron HT (activa o pasiva), aumentando los que recibieron HT activa del 78% en 2012 al 85% en 2013 (p = 0.01). El 14% no recibió HT principalmente por retraso en el diagnóstico o en el traslado, o por no indicarse el tratamiento. El 57% de los RN nació en hospitales sin HT, siendo el traslado en hipotermia pasiva; en el 39% por equipos sin formación adecuada. En junio del 2015, 57/90 centros realizaban HT: 54 HT corporal total activa (todos con dispositivos servocontrolados). Existió heterogeneidad en la distribución por comunidades autónomas (CC. AA.) de centros con HT activa y en el número de RN que recibieron HT. Conclusiones: La incidencia de EHI moderada-grave es homogénea entre CC. AA. Aunque se constata un importante progreso en la implementación de la HT, es preciso mejorar la disponibilidad de HT activa entre CC. AA., así como el diagnóstico precoz y el traslado con garantías desde los centros emisores.

Objective To describe the results in terms of audiometric relapse-free survival and relapse rate in immunomediated hearing loss patients treated exclusively with corticosteroids. Method Retrospective study of patients with audiometric relapses, monitored from 1995 to 2014, in two centres of the Community of Madrid. Results We evaluated 31 patients with a mean age of 48.52 years (14.67 SD), of which 61.3% were women. Most hearing loss was fluctuating (48.4%). Only 16.1% of patients had systemic autoimmune disease. There is a moderate positive correlation between the sex variable and the systemic involvement variable (Spearman's correlation coefficient = 0.356): specifically, between being female and systemic disease. The relative incidence rate of relapse in the first year was 2.01 relapses/year with a 95% CI (1.32–2.92). The mean survival time of the event (audiometric relapse) was 5.25 months (SD 0.756). With multivariate analysis, the only variable that achieved statistical significance was age, with a hazard ratio of 1.032 (95% CI; 1.001–1.063, P = .043). Conclusions Immune-mediated disease of the inner ear is a chronic disease with relapses. Half of the patients with immunomediated hearing loss treated exclusively with corticosteroids relapse before 6 months of follow-up. In addition, if a patient has not relapsed, they are more likely to relapse as each year passes. Analysis of the audiometric relapse-free survival will enable the effect of future treatments to be compared and their capacity to reduce the rhythm of relapses.

The aim of this study was to examine the association between the consumption of total and specific types of dairy products and the risk of incident cataracts in an elderly Mediterranean population at high cardiovascular risk. We prospectively analyzed 5860 subjects from the PREvencion con DIeta MEDiterranea (PREDIMED) Study. The time to cataract surgery was calculated as the time between recruitment and the date of the surgery, last visit of the follow-up, date of death, or until the end of the study. Dairy products intake was assessed using validated food frequency questionnaires. We used Cox proportional hazard regression to assess the risk of cataract surgery according to average dietary energy-adjusted total dairy products, milk, yogurt and cheese consumption. We documented a total of 768 new cataract events after a median of 5.6 years of follow-up. Subjects in the second [hazard ratio (HR) 0.62; 95% CI 0.52, 0.74] and third tertile (HR: 0.71; 95% CI 0.60, 0.85) of skimmed yogurt intake had a significantly lower risk of cataracts after adjusting for potential confounders. No significant associations were observed for total dairy products, whole and skimmed milk, whole yogurt and cheese consumption. The intake of skimmed yogurt was associated with a reduced risk of cataracts in an elderly Mediterranean population with high cardiovascular risk. No significant associations were observed for other type of dairy product. International Standard Randomized Controlled Trial Number (ISRCTN): 35739639. Registration date: 5 October 2005.

Data on the incidence of hypoxic-ischemic encephalopathy (HIE) in the first 6 hours of life together with the implementation of therapeutic hypothermia (TH) are relevant to delineate actions to achieve the lowest rates of neonatal mortality, morbidity, and long-term impact on health associated with HIE. This is population-based national survey study, including newborns ≥35 weeks of gestation with moderate-to-severe HIE from all level III neonatal care units, to provide the incidence of HIE for the period 2012-2013, and the implementation of TH up to June 2015 in Spain. Incidence rate was 0.77 per 1000 live births (95% confidence interval 0.72-0.83). By June 2015, 63% (57/90) of the units had implemented TH; 95% of them performed servo-controlled whole-body TH. For the 2-year period, 86% of the newborns diagnosed with moderate-to-severe HIE received TH. Active TH increased in use from 78% in 2012 to 85% in 2013 (p = 0.01). The main reasons for not cooling were a delay in the diagnosis (31/682) and the fact that the treatment was not offered (20/682). Interhospital patient transfer was performed using passive hypothermia, by appropriately trained personnel in 61% of centers. Eighteen percent of newborns with moderate or severe HIE died, without significant differences between the 2 years. Up-to-date knowledge of the national coverage of neonatal care of infants with HIE in developed countries is a prerequisite to reducing the load of HIE in this area and to facilitating coordinated, eliminate investigation.

[EN] Nowadays, Spanish two-lane rural roads frequently accommodate sport cyclists. They usually ride on the shoulder or on the right edge of the lane, sharing the infrastructure with motorised vehicles. Due to the speed difference between road users, the most frequent and dangerous interaction is in overtaking manoeuvres. One key factor from a safety and traffic operation point of view is the overtaking duration. The main aim of this paper is to analyse how factors related to the road, the cyclists, and the overtaking manoeuvre influence the duration of overtaking to cyclists on two-lane rural roads. Naturalistic field data were obtained using instrumented bicycles. Seven groups of cyclists, formed by different numbers of cyclists riding in-line and two-abreast, rode along five rural roads with different geometric and traffic characteristics. A total of 1592 flying manoeuvres, in which drivers did not reduce their speed, and 192 accelerative manoeuvres were analysed. The overtaking duration, considering each overtaking strategy, was modelled using Bayesian statistics. Results showed that flying manoeuvres were more prevalent than accelerative. They were performed with higher speeds and lower lateral clearances and, therefore, presented lower overtaking durations. For both overtaking strategies, duration increased on wider roads and with a larger size of the group. The presence of an oncoming vehicle decreased the overtaking duration. However, other factors presented opposite effects on the duration depending on the overtaking strategy. The developed predictive models allow obtaining overtaking durations varying road and cyclist grouping characteristics. Results can be used by road administration to manage and propose some specific countermeasures to integrate the cyclists in a safe and efficient way on two-lane rural roads., This research was part of the project "Improvement of safety and operation of two-lane rural roads with cyclists (Bike2Lane)" (TRA2016-80897-R) funded by the Spanish Ministry of Science and Innovation. The research collaboration was funded by the Agencia Estatal de Investigacion "Ayudas para contratos predoctorales para la formacion de doctores 2017" (BES-2017-080474).

Introduction: Postnatal growth restriction is considered a universal problem in extremely premature infants (EPI), and causes great concern due to the possible relationship between nutrition, sub-optimal postnatal growth, and neurodevelopment delay. Objectives: To describe the weight gain in EPI and to determine the changes in the length and head circumference (HC) at hospital discharge in survivors. Patients and methods: The study included 4520 Caucasian EPI from single pregnancies and without severe malformations, born in the centres participating in the Spanish SEN1500 network (2002–2011). The weight was recorded at birth, 28 days, 36 weeks post-menstrual age (PMA), and at discharge. The length and HC were measured at birth and at discharge. Results: The rate of weight gain (exponential method) was 8.0 g/kg/day (birth to 28 days); 14.3 g/kg/day (28 days to 36 weeks); and 11.7 g/kg/day (36 weeks to discharge). At discharge, postnatal growth restriction was greater for length (z-score between −1.78 and −2.42, depending on GA), followed by weight (−1.67 to −1.79), and HC (−0.69 to −0.81). Conclusions: Weight gain in the first weeks after birth is slow in EPI, and they exhibit an almost universal postnatal growth restriction that involves mainly length and weight. In addition to weight, a close control of longitudinal growth and HC are essential for nutritional assessment and detection of patients at risk for poor growth and neurodevelopment after hospital discharge. Resumen: Introducción: La restricción posnatal del crecimiento es considerada un problema universal en recién nacidos extremadamente prematuros (RNEP), generando gran preocupación debido a la posible relación entre nutrición, crecimiento posnatal subóptimo y alteraciones del neurodesarrollo. Objetivos: Describir la evolución de la ganancia posnatal de peso en RNEP y conocer los cambios en la longitud y el perímetro craneal (PC) al alta hospitalaria en los supervivientes. Pacientes y métodos: Se estudió a 4.520 RNEP de raza blanca, de gestaciones únicas y sin malformaciones, nacidos en los centros participantes en la red española SEN1500 (2002-2011). El peso se registró al nacimiento, 28 días, 36 semanas de edad posmenstrual y al alta hospitalaria. La longitud y el PC se estudiaron al nacimiento y al alta. Resultados: La velocidad de ganancia ponderal fue de 8,0 g/kg/día (nacimiento-28 días); 14,3 g/kg/día (28 días-36 semanas), y 11,7 g/kg/día (36 semanas-alta hospitalaria). Al alta, la restricción posnatal del crecimiento fue mayor para la longitud (z-score entre −1,78 y −2,42, en función de la edad gestacional), seguida del peso (−1,67 a −1,79) y, finalmente, el PC (−0,69 a −0,81). Conclusiones: Los RNEP presentan una velocidad de ganancia ponderal lenta en las primeras semanas tras el nacimiento y una restricción posnatal del crecimiento que afecta en mayor grado a la longitud y al peso. Además del peso, un control estrecho del crecimiento longitudinal y del PC es fundamental para la valoración nutricional y la detección de pacientes de riesgo respecto al crecimiento y el neurodesarrollo tras el alta hospitalaria.

The objective of this study was to evaluate the heritability of neonatal arterial ischemic stroke (NAIS) in relation to family history of thromboembolic event, maternal diseases, and thrombophilia in both parents ( F5G1691A, F2G20210A, and MTHFRC677 T mutations). Forty-two consecutive infants ≥36 weeks of gestation

Purpose We sought to determine if specific genetic single nucleotide polymorphisms (SNPs) influence vascular endothelial growth factor inhibition response to ranibizumab in neovascular age-related macular degeneration (AMD). Methods A total of 403 Caucasian patients diagnosed with exudative AMD were included. After a three-injection loading phase, a pro re nata regimen was followed. Nine SNPs from six different genes (CFH, CFB, ARMS2, SERPINF1, VEGFR1, VEGF) were genotyped. Non-genetic risk factors (gender, smoking habit and hypertension) were also assessed. Patients were classified as good or poor responders (GR or PR) according to functional (visual acuity), anatomical (foveal thickness measured by OCT) and fluid criteria (fluid/no fluid measured by OCT). Results Hypertension was the environmental factor with the strongest poor response association with ranibizumab in the anatomical measure after the loading phase (p = 0.0004; OR 3.7; 95% CI, 2.4–5.8) and after 12 months of treatment (p = 10−5; OR 2.3; 95% CI, 1.5–3.4). The genetic variants rs12614 (CFB), rs699947 (VEGFA) and rs7993418 (VEGFR1) predisposed patients to a good response, while rs12603486 and rs1136287 (SERPINF1) were associated with a poor response. The protective genotype of rs800292 variant (CFH) was also associated with a poor anatomical response (p 0.0048). Conclusion All these data suggest that genetics play an important role in treatment response in AMD patients.

Brain imaging methods such as functional Magnetic Resonance Imaging (fMRI) and Diffusion Tensor Imaging (DTI) have already been used to decipher the functional and structural brain changes occurring during normal language development. However, little is known about the differentiation of the language network after an early lesion. While in adults, stroke over the left hemisphere generally induces post-stroke aphasia, it is not always the case when a stroke occurs in the perinatal period, thus revealing a remarkable plastic power of the language network during early development. In particular, the role of perilesional tissues, as opposed to undamaged brain areas in the functional recovery of language functions after an early insult, remains unclear. In this review article, we provide an overview of the extant literature using functional and structural neuroimaging data revealing the signatures of brain plasticity underlying near-normal language development.

Objectives To investigate whether cerebrospinal fluid levels of neuron-specific enolase (CSF-NSE) during the first 72 hours correlate with other tools used to assess ongoing brain damage, including clinical grading of hypoxic-ischemic encephalopathy (HIE), abnormal patterns in amplitude integrated electroencephalography (aEEG), and magnetic resonance imaging (MRI), as well as with the neurodevelopmental outcomes at two years of age. Material and methods Prospective observational study performed in two hospitals between 2009 and 2011. Forty-three infants diagnosed with HIE within 6 hours of life were included. HIE was severe in 20 infants, moderate in 12, and mild in 11. Infants with moderate-to-severe HIE received whole-body cooling. Both the HIE cohort and a control group of 59 infants with suspected infection underwent measurement of CSF-NSE concentrations at between 12 and 72 hours after birth. aEEG monitoring was started at admission and brain MRI was performed within the first 2 weeks. Neurodevelopment was assessed at 24 months. Results The HIE group showed higher levels of CSF-NSE than the control group: median 70 ng/ml (29; 205) vs 10.6 ng/ml (7.7; 12.9); p

International audience; Objective: COVID-19 patients may present mild symptoms. The identification of paucisymptomatic patients is paramount in order to interrupt the transmission chain of the virus. Olfactory loss could be one of those early symptoms which might help in the diagnosis of COVID-19 patients. In this study, we aim to develop and validate a fast, inexpensive, reliable and easy-to-perform olfactory test for the screening of suspected COVID-19 patients. Study design: Phase I was a case–control study and Phase II a transversal descriptive study. Subjects and methods: Olfaction was assessed with the ethyl alcohol threshold test and symptoms with visual analogue scales. The study was designed in two phases: In Phase I, we compared confirmed COVID-19 patients and healthy controls. In Phase II, patients with suspected COVID-19 infection referred for testing were studied. Results: 275 participants were included in Phase I, 135 in Phase II. The ROC curve showed an AUC of 0.749 in Phase I, 0.737 in Phase II. The cutoff value which offered the highest amount of correctly classified patients was ≥ 2 (10% alcohol) for all age intervals. The odds ratio was 8.19 in Phase I, 6.56 in Phase II with a 75% sensitivity. When cases report normal sense of smell (VAS < 4), it misdiagnoses 57.89% of patients detected by the alcohol threshold test. Conclusion: The olfactory loss assessed with the alcohol threshold test has shown high sensitivity and odds ratio in both patients with confirmed COVID-19 illness and participants with suspected SARS-CoV-2 infection.

Treatment of congenital cytomegalovirus infection is mandatory in cases with severe systemic and/or neurological involvement. However, some patients are paucisymptomatic, with very subtle systemic manifestations and/or minimal brain alterations. Current international guidelines do not clearly state whether these children should be treated, and this decision is not straightforward for clinicians. Of a small series of six infants with congenital cytomegalovirus infection admitted to our neonatal unit between 2015 and 2019, half showed paucisymptomatic neurological manifestations. In these cases, the determination of s2-microglobulin in cerebrospinal fluid and magnetic resonance imaging aided in the decision-making concerning the therapeutic approach to follow.