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Background: Fatal anaphylaxis is very rare, with an incidence ranging from 0.5 to 1 deaths per million person-years. Objective: Based on a systematic review, we aimed to explain differences in the reported incidence of fatal anaphylaxis based on the methodological and demographic factors addressed in the various studies. Methods: We searched PubMed/MEDLINE, EMBASE, and the Web of Science for relevant retrospective and prospective cohort studies and registry studies that had assessed the anaphylaxis mortality rate for the population of a country or for an administrative region. The research strategy was based on combining the term “anaphylaxis” with “death”, “study design”, and “main outcomes” (incidence). Results: A total of 46 studies met the study criteria and included 16,541 deaths. The range of the anaphylaxis mortality rate for all causes of anaphylaxis was 0.002-2.51 deaths per million person-years. Fatal anaphylaxis due to food (range 0.002-0.29) was rarer than deaths due to drugs (range 0.004-0.56) or Hymenoptera venom (range 0.02-0.61). The frequency of deaths due to anaphylaxis by drugs increased during the study period (IRR per year, 1.02; 95%CI, 1.00-1.04). We detected considerable heterogeneity in almost all of the meta-analyses carried out. Conclusion: The incidence of fatal anaphylaxis is very low and differs according to the various subgroups analyzed. The studies were very heterogeneous. Fatal anaphylaxis due to food seems to be less common than fatal anaphylaxis due to drugs or Hymenoptera venom.

Lung cancer (LC) is the most frequent and deadly neoplasm in the world, and patients have shown a tendency to have more emotional distress than other cancer populations. Dignity Therapy (DT) is a brief intervention aimed to improve emotional well-being in patients facing life-threatening illness.ObjectiveTo analyze the effect of DT on anxiety, depression, hopelessness, emotional distress, dignity-related distress, and quality of life (QoL) in a group of Mexican patients with stage IV LC undergoing active medical treatment with baseline emotional distress.MethodIn this preliminary pretest–posttest study, patients received three sessions of DT and were evaluated with the HADS, Distress Thermometer, Patient Dignity Inventory, single-item questions, and QLQ-30.ResultsIn total, 24 out of 29 patients completed the intervention. Statistically significant improvements were found in anxiety, depression, emotional distress, hopelessness, and dignity-related distress with large effect sizes. Patients reported that DT helped them, increased their meaning and purpose in life, their sense of dignity, and their will to live, while it decreased their suffering. No changes were found in QoL.Significance of resultsDT was well accepted and effective in improving the emotional symptoms of LC patients with distress that were undergoing medical treatment. Although more research is warranted to confirm these results, this suggests that DT can be used in the context of Latin-American patients.

Objectives We designed and conducted a narrative review consistent with the PRISMA guidelines (PROSPERO registration number: CRD42018099498) to evaluate the association between environmental metals (manganese, mercury, iron) and Parkinson’s Disease (PD) in low and middle-income countries (LMIC). Methods Data sources: A total of 19 databases were screened, and 2,048 references were gathered. Study selection: Randomized controlled trials, cluster trials, cohort studies, case-control studies, nested case-control studies, ecological studies, cross-sectional studies, case series, and case reports carried out in human adults of LMIC, in which the association between at least one of these three metals and the primary outcome were reported. Data extraction: We extracted qualitative and quantitative data. The primary outcome was PD cases, defined by clinical criteria. A qualitative analysis was conducted. Results Fourteen observational studies fulfilled the selection criteria. Considerable variation was observed between these studies’ methodologies for the measurement of metal exposure and outcome assessment. A fraction of studies suggested an association between the exposure and primary outcome; nevertheless, these findings should be weighted and appraised on the studies’ design and its implementation limitations, flaws, and implications. Conclusions Further research is required to confirm a potential risk of metal exposure and its relationship to PD. To our awareness, this is the first attempt to evaluate the association between environmental and occupational exposure to metals and PD in LMIC settings using the social determinants of health as a framework.

Malocclusions, according to the World Health Organization (WHO), rank third as oral health problems. The aim of this research work was to determine the frequency of malocclusion present in 6 to 12 years old children in the city of Coronel Oviedo, Paraguay in 2016.A descriptive observational study with analytic component was performed in the children that had the first permanent upper and lower molar in at least one hemiarch, who presented the informed consent signed by the parents. The outcomes were malocclusion, molar and canine relation, overjet and overbite, crowding and crossbite. The data was loaded into an Excel spreadsheet and analyzed with the Stata 14 program. Malocclusion was found in 66% of the children, 85.7% presented molar and canine Class I, 44.6% normal overbite, 35.7% normal overjet, 55.4% crowding, 8.9% presented crossbite, 75% straight profile, 62.5% deviation from the midline. In relation to age (p=3.2) and sex (p=0.4), no statistically significant associations were found in relation with malocclusion. The frequency of malocclusion in schoolchildren from Coronel Oviedo, Paraguay was high

10 pags., 7 figs., 1 tab., PURPOSE: To measure monochromatic aberrations at various wavelengths in eyes implanted with the Clareon monofocal aspheric intraocular lens (IOL) (Alcon Laboratories, Inc., Fort Worth, TX). The authors estimated longitudinal chromatic aberration (LCA), modulation transfer functions (MTFs), and the impact of interactions between chromatic and monochromatic aberrations on retinal image quality. METHODS: Ten patients (age: 68.4 ± 3.21 years) were measured in two experiments: (1) Hartmann-Shack wave aberrations at five visible wavelengths (480 to 700 nm) and (2) best subjective focus at each wavelength. Objective and psychophysical LCAs were obtained from the Zernike defocus and psychophysical best focus, respectively. MTFs were calculated for the closest wavelengths to the peak sensitivity of the three cone classes (S [480 nm], M [555 nm], and L [564 nm]) using the measured aberrations and chromatic difference of focus. The degradation produced by LCA was estimated as the visual Strehl ratio for green divided by the visual Strehl ratio for blue and red. RESULTS: The root mean square for higher order aberrations (HOAs) ranged from 0.0622 to 0.2084 µm (700 nm, 4.3-mm pupil). Monochromatic visual Strehl ratio was above 0.35 in all patients. LCA was 1.23 ± 0.05 diopters (D) (psychophysical) and 0.90 ± 0.11 D (objective). Visual Strehl ratio decreased by a factor ranging from 1.38 to 3.82 on chromatic defocus from green to blue. There was a significant correlation between native visual Strehl ratio and the degradation produced by LCA (ie, visual Strehl/visual Strehl). CONCLUSIONS: The Clareon IOL compensates for spherical aberration, with postoperative wave aberrations dominated by astigmatism and other HOAs, being highly subject-dependent. The impact of LCA in blue is largely dependent on the magnitude of monochromatic aberrations., Supported by ERC Grant Agreement (ERC-2011-AdG-294099) and Spanish Government grant FIS 2017-84753 (SM); Spanish Ministry of Science Aids for recruiting Technical Support Personnel PTA2017-13787-I (MR), and Madrid Regional Government Spanish Ministry of Science Aids for recruiting Technical Support Personnel PTA2017-13787-I (AG-R). The study was partially funded by a Research Collaborative Agreement with Alcon Research Labs.

The aim of this document is to review the epidemiology of anaphylaxis in the emergency departments (EDs) (burden and temporal trends), the generally deficient management of anaphylaxis in the ED, and the measures and interventions tested in different settings to improve management of anaphylaxis in the ED. The population attended for anaphylaxis episodes is low (0.009 to 0.4%). Recent studies report an increase in anaphylaxis episodes attended in the ED. Discordance has been observed between the diagnosis of anaphylaxis in the ED and the diagnosis confirmed in allergy units; this can reach 45%. Management of anaphylaxis is not consistent with international guidelines, and the lack of adherence to guidelines affects the use of epinephrine in the ED, prescription of epinephrine autoinjectors, initial advice on avoidance, and referral to an allergist. Measures to improve the management of anaphylaxis have proven effective. The low burden of anaphylaxis in the ED and the disappointing landscape of management of this syndrome in the ED should drive strategies aimed at providing staff with key concepts and measures that enable them to manage episodes of anaphylaxis effectively.

Gamma-aminobutyric acid (GABA)-releasing interneurons modulate neuronal network activity in the brain by inhibiting other neurons. The alteration or absence of these cells disrupts the balance between excitatory and inhibitory processes, leading to neurological disorders such as epilepsy. In this regard, cell-based therapy may be an alternative therapeutic approach. We generated light-sensitive human embryonic stem cell (hESC)-derived GABAergic interneurons (hdIN) and tested their functionality. After 35 days in vitro (DIV), hdINs showed electrophysiological properties and spontaneous synaptic currents comparable to mature neurons. In co-culture with human cortical neurons and after transplantation (AT) into human brain tissue resected from patients with drug-resistant epilepsy, light-activated channelrhodopsin-2 (ChR2) expressing hdINs induced postsynaptic currents in human neurons, strongly suggesting functional efferent synapse formation. These results provide a proof-of-concept that hESC-derived neurons can integrate and modulate the activity of a human host neuronal network. Therefore, this study supports the possibility of precise temporal control of network excitability by transplantation of light-sensitive interneurons.

Simple Summary Atrial fibrillation is a type of arrhythmia that occurs when the electrical activity of the heart in the atrium is not coordinated, and its consequences can be lethal. The driving source that initiates this chaotic activity can be located anywhere in the atrium, but most frequently appears in certain areas such as the pulmonary veins. In this study, we developed a new estimation method to evaluate possible source location and complexity of the arrhythmia using computer simulations. This method represents mathematical descriptions of natural processes that can be used to mimic a real scenario, including specific information such as the atrial anatomy. Here, we identified a specific biomarker the enabled obtaining a foci distribution map and found that elimination of pulmonary vein drivers was associated with a successful long-term ablation outcome. This study could, therefore, help to identify and characterize patients in order to better plan the ablation procedure. Abstract Current clinical guidelines establish Pulmonary Vein (PV) isolation as the indicated treatment for Atrial Fibrillation (AF). However, AF can also be triggered or sustained due to atrial drivers located elsewhere in the atria. We designed a new simulation workflow based on personalized computer simulations to characterize AF complexity of patients undergoing PV ablation, validated with non-invasive electrocardiographic imaging and evaluated at one year after ablation. We included 30 patients using atrial anatomies segmented from MRI and simulated an automata model for the electrical modelling, consisting of three states (resting, excited and refractory). In total, 100 different scenarios were simulated per anatomy varying rotor number and location. The 3 states were calibrated with Koivumaki action potential, entropy maps were obtained from the electrograms and compared with ECGi for each patient to analyze PV isolation outcome. The completion of the workflow indicated that successful AF ablation occurred in patients with rotors mainly located at the PV antrum, while unsuccessful procedures presented greater number of driving sites outside the PV area. The number of rotors attached to the PV was significantly higher in patients with favorable long-term ablation outcome (1-year freedom from AF: 1.61 ± 0.21 vs. AF recurrence: 1.40 ± 0.20; p-value = 0.018). The presented workflow could improve patient stratification for PV ablation by screening the complexity of the atria.

The aim of this document is to review the epidemiology, diagnosis, and treatment of immediate and anaphylactic reactions to gadolinium-based contrast agents (GBCA) most commonly used in magnetic resonance imaging (MRI). The frequency of adverse reactions to GBCA ranges from 0.04 to 2.2%. Most reactions are mild (47%–95%) and the frequency of anaphylactic shock is 0.004%–0.01%. Mortality due to anaphylaxis induced by GBCAs has been 0.0019%. Allergic reactions are more frequent in patients with a previous reaction, in females, using macrocycle estructure GBCA and with hepatic, abdominal, and thoracic examinations. Determination of tryptase in the acute phase, and allergy study could confirm the culprit drug and assess the use of an alternative GBCA. Allergic reactions, including anaphylaxis, can be resolved with appropriate training, early identification, and suitable equipment, especially in radiology departments. Anaphylaxis to GBCA is extremely rare. A history of previous reactions to GBCA is the main risk factor for a new reaction. In patients who have previously experienced a reaction, it is recommended to perform an allergological study to establish or rule out allergy to GBCAs and to assess the use of an alternative GBCA if necessary.

Background Darunavir/cobicistat can be used as mono, dual, triple or more than triple therapy. Objectives To assess factors associated with the number of drugs in darunavir/cobicistat regimens. Methods A nationwide retrospective cohort study of consecutive HIV-infected patients initiating darunavir/cobicistat in Spain from July 2015 to May 2017. Baseline characteristics, efficacy and safety at 48 weeks were compared according to the number of drugs used. Results There were 761 patients (75% men, 98% were antiretroviral-experienced, 32% had prior AIDS, 84% had HIV RNA Discussion Darunavir/cobicistat use in Spain has been tailored according to clinical characteristics of HIV-infected patients. Monotherapy and dual therapy have been common and preferentially addressed to older patients with a better HIV status, suggesting that health issues other than HIV infection may have been strong determinants of its prescription.

Background Although pregnancy is frequently associated with mental states of happiness, hope and well-being, some physical and psychological changes can contribute to increased sleep disturbances and worsened sleep quality. Sleep quality has been linked to negative emotions, anxiety and depression. The main objective of this paper was to systematically review the impact of sleep during pregnancy on maternal mood, studying the association between objective and subjective measures of sleep quality and perinatal depression. Methods We performed a systematic review according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, which included studies published between January 2008 and April 2019, and met the following criteria: (i) studies on pregnant women assessing the effects of sleep quality variables on perinatal mood disorders, (ii) studies published in English and (iii) full paper published in a peer-reviewed scientific journal with full-text format available. Results A total of 36 studies published in the last decade met the inclusion criteria for qualitative review and eight of them were suitable for meta-analysis. Both confirmed the negative effects of poor sleep on perinatal mood. However, qualitative analysis showed that unrepresentative samples and low participation rates falling below 80% biased some of the studies. The standard random-effects meta-analysis showed a pooled size effect [ln odds ratio (OR) 1.49 (95% confidence interval [CI] 1.19, 1.79)] for perinatal depression in cases of poor prenatal sleep quality, although heterogeneity was moderate to high [Q 16.05, P ≤ 0.025, H2 2.45 (95% CI 1.01, 13.70)]. Conclusion Poor sleep quality was associated with perinatal mood disturbances. The assessment of sleep quality along the pregnancy could be advisable with a view to offering preventative or therapeutic interventions when necessary.

The role of auxin in the fruit-ripening process during the early developmental stages of commercial strawberry fruits (Fragaria x ananassa) has been previously described, with auxin production occurring in achenes and moving to the receptacle. Additionally, fruit softening is a consequence of the depolymerization and solubilization of cell wall components produced by the action of a group of proteins and enzymes. The aim of this study was to compare the effect of exogenous auxin treatment on the physiological properties of the cell wall-associated polysaccharide contents of strawberry fruits. We combined thermogravimetric (TG) analysis with analyses of the mRNA abundance, enzymatic activity, and physiological characteristics related to the cell wall. The samples did not show a change in fruit firmness at 48 h post-treatment, by contrast, we showed changes in the cell wall stability based on TG and differential thermogravimetric (DTG) analysis curves. Less degradation of the cell wall polymers was observed after auxin treatment at 48 h post-treatment. The results of our study indicate that auxin treatment delays the cell wall disassembly process in strawberries.

In this study we profiled vaccine-induced polyclonal antibodies as well as plasmablast derived mAbs from individuals who received SARS-CoV-2 spike mRNA vaccine. Polyclonal antibody responses in vaccinees were robust and comparable to or exceeded those seen after natural infection. However, the ratio of binding to neutralizing antibodies after vaccination was greater than that after natural infection and, at the monoclonal level, we found that the majority of vaccine-induced antibodies did not have neutralizing activity. We also found a co-dominance of mAbs targeting the NTD and RBD of SARS-CoV-2 spike and an original antigenic-sin like backboost to seasonal human coronaviruses OC43 and HKU1. Neutralizing activity of NTD mAbs but not RBD mAbs against a clinical viral isolate carrying E484K as well as extensive changes in the NTD was abolished, suggesting that a proportion of vaccine induced RBD binding antibodies may provide substantial protection against viral variants carrying single E484K RBD mutations., An analysis of mRNA vaccine-induced polyclonal antibodies and plasmablast derived monoclonal antibodies from individuals vaccinated against SARS-CoV-2 identifies a high proportion of non-neutralizing antibodies, the induction of cross-reactive antibodies to seasonal coronaviruses and also maps the regions in the spike protein that are targeted, even among viral variants.

Objective: To study changes in supraspinatus tendon elasticity after a 448 kHz capacitive resistive monopolar radiofrequency (CRMR) intervention in professional badminton players. Design: Double-blinded randomized clinical trial. Setting: All participants were recruited in a private care practice. Participants were randomized to receive either a CRMR treatment (n ¼ 19) or placebo (n ¼ 19). Subjects: Professional badminton players (n ¼ 38). Intervention: A total of nine intervention (three per week) with CRMR at 448 kHz were carried out in the experimental group. The same intervention without an active CRMR current was carried out in the control group. Main measures: Mean values of three different regions of the supraspinatus tendon were reported at baseline (T1), immediately after the intervention (T2) and one week after the end of the whole intervention program (T3) using quantitative ultrasound strain elastography (SEL). Results: There were statistically significant differences in the supraspinatus tendon elasticity immediately after the intervention (p¼

[EN] Background Multipoint pacing (MPP) in cardiac resynchronization therapy (CRT) activates the left ventricle from two locations, thereby shortening the QRS duration and enabling better resynchronization; however, compared with conventional CRT, MPP reduces battery longevity. On the other hand, electrocardiogram-based optimization using the fusion-optimized intervals (FOI) method achieves more significant reverse remodeling than nominal CRT programming. Our study aimed to determine whether MPP could attain better resynchronization than single-point pacing (SPP) optimized by FOI. Methods This prospective study included 32 consecutive patients who successfully received CRT devices with MPP capabilities. After implantation, the QRS duration was measured during intrinsic rhythm and with three pacing configurations: MPP, SPP-FOI, and MPP-FOI. In 14 patients, biventricular activation times (by electrocardiographic imaging, ECGI) were obtained during intrinsic rhythm and for each pacing configuration to validate the findings. Device battery longevity was estimated at the 45-day follow-up. Results The SPP-FOI method achieved greater QRS shortening than MPP (-56 +/- 16 vs. -42 +/- 17 ms, p < .001). Adding MPP to the best FOI programming did not result in further shortening (MPP-FOI: -58 +/- 14 ms, p = .69). Although biventricular activation times did not differ significantly among the three pacing configurations, only the two FOI configurations achieved significant shortening compared with intrinsic rhythm. The estimated battery longevity was longer with SPP than with MPP (8.1 +/- 2.3 vs. 6.3 +/- 2.0 years, p = .03). Conclusions SPP optimized by FOI resulted in better resynchronization and longer battery duration than MPP., Centro de Investigacion Biomedica en Red Enfermedades Cardiovasculares, Grant/Award Number: CB16/11/00354; Instituto de Salud Carlos III, Grant/Award Numbers: DTS16/0160, PI16/00435, PI16/00703, PI17/01059, PI17/01106; Sociedad Espanola de Cardiologia, Grant/Award Numbers: 2018, SEC_ESTIM_01; Agencia deGestio d'Ajuts Universitaris i de Recerca, Grant/AwardNumber: 2017_SGR_1548; Fundacio laMarato de TV3, Grant/Award Number: 20152730; Horizon 2020 Framework Programme, Grant/Award Number: 633196 - CATCH MEproject; European Regional Development Fund, Grant/Award Number: EITHealth 19600 AFFINE

Noninvasive electrocardiographic imaging (ECGi) is a useful tool that can be used to guide ablation procedures in atrial fibrillation (AF patients). Most ECGi resolutions are based on the Boundary Element Method, and thus application of Green's theorem, that requires that electrical sources reside inside a closed volume. The objective of this work is to quantify the error in atrial fibrillation metrics than can be expected if two volumes are segmented for the atria instead of just one. Our results show that segmenting the atria of the patients into two volumes instead of one does impact on rotor-related AF metrics that can be derived from ECGi whereas dominant-frequency metrics are less affected.

PURPOSE: To measure the in vivo longitudinal chromatic aberration (LCA) from the chromatic difference of focus (480 to 700 nm) using psychophysical methods in patients bilaterally implanted with a hydrophobic trifocal intraocular lens (IOL). METHODS: Psychophysical best focus was measured in both eyes at different wavelengths (480 to 700 nm) and at three different viewing distances (0.00, +1.75, and +3.50 diopters [D]) using a custom-developed polychromatic adaptive optics set-up provided with a supercontinuum laser, a Hartmann-Shack wavefront sensor, a deformable mirror, a motorized Badal system, a pupil monitoring system, and a psychophysical channel with monochromatically illuminated stimuli. Measurements were performed on 10 patients (20 eyes) bilaterally implanted with hydrophobic trifocal diffractive IOLs (FineVisionHP POD F GF; PhysIOL). LCA was computed from the chromatic difference of focus curves as the difference between 480 and 700 nm at near, intermediate, and far. RESULTS: The LCA from psychophysical measurements was significantly higher for far vision (0.99 ± 0.06 diopters [D]), than for intermediate (0.67 ± 0.10 D) and near (0.23 ± 0.08 D) vision (one-way analysis of variance, P < .05). CONCLUSIONS: LCA for far vision was significantly higher than for intermediate and near vision in hydrophobic trifocal diffractive IOLs, in agreement with a previous study with the same optical design but hydrophilic material IOLs. The LCA for the hydrophobic IOL is slightly higher than for the hydrophilic IOL at far. Different combinations of refractive and diffractive LCA will allow optimizing IOL designs to improve polychromatic image quality., Supported by Spanish Government Grant No. FIS 2017-84753 to Dr. Marcos, and FPU Predoctoral Fellowship No. FPU16/01944 to Ms. Aissati.

We developed and pilot-tested an eight-session community-based cognitive behavior therapy group intervention to improve coping with intersectional stigma, address medical mistrust, and improve antiretroviral treatment adherence. Seventy-six HIV-positive Latinx sexual minority men (SMM; 38 intervention, 38 wait-list control) completed surveys at baseline, and 4- and 7-months post-baseline. Adherence was electronically monitored. Intention-to-treat, repeated-measures regressions showed improved adherence in the intervention vs. control group from baseline to follow-up [electronically monitored: b (95% CI) 9.24 (- 0.55, 19.03), p = 0.06; self-reported: b (95% CI) 4.50 (0.70, 8.30), p = .02]. Intervention participants showed marginally decreased negative religious coping beliefs in response to stigma [b (95% CI) = - 0.18 (- 0.37, 0.01), p = .06], and significantly lower medical mistrust [b (95% CI) = - 0.47 (- 0.84, - 0.09), p = .02]. Our intervention holds promise for improving HIV outcomes by empowering Latinx SMM to leverage innate resilience resources when faced with stigma.ClinicalTrials.gov ID (TRN): NCT03432819, 01/31/2018.Hemos desarrollado un estudio piloto para poner a prueba un programa de ocho-sesiones de terapia cognitivo-conductual basado en un grupo de comunidad para abordar el estigma interseccional, la desconfianza médica y mejorar la adherencia al tratamiento antirretroviral. Setenta y seis hombres Latinos de minorías sexuales VIH positivos (38 en el grupo de intervención, 38 en el grupo de control de lista de espera) completaron encuestas al inicio, y cuatro y siete meses después de la línea de base. La adherencia fue medida electrónicamente. Los resultados del análisis mostraron una mejor adherencia en el grupo de intervención en comparación al grupo de control desde el inicio hasta el seguimiento [monitoreado electrónicamente: b (95% IC) 9.24 (− 0.55, 19.03), p = .06; y autoreporte: b (95% IC) 4.50 (0.70, 8.30), p = .02]. Los participantes del grupo de intervención mostraron una disminución marginal en las creencias negativas de afrontamiento religioso al estigma [b (95% IC) − 0.18 (− 0.37, 0.01), p = .06], y significativamente menor desconfianza médica [b (95% IC) − 0.47 (− 0.84, − 0.09), p = .02]. Nuestra intervención es prometedora para mejorar los resultados del VIH al empoderar a hombres Latinos de minorías sexuales para tomar ventaja de los recursos de resiliencia innatos cuando se enfrentan al estigma.

Background: Multipoint pacing (MPP) in cardiac resynchronization therapy (CRT) activates the left ventricle from two locations, thereby shortening the QRS duration and enabling better resynchronization; however, compared with conventional CRT, MPP reduces battery longevity. On the other hand, electrocardiogram-based optimization using the fusion-optimized intervals (FOI) method achieves more significant reverse remodeling than nominal CRT programming. Our study aimed to determine whether MPP could attain better resynchronization than single-point pacing (SPP) optimized by FOI. Methods: This prospective study included 32 consecutive patients who successfully received CRT devices with MPP capabilities. After implantation, the QRS duration was measured during intrinsic rhythm and with three pacing configurations: MPP, SPP-FOI, and MPP-FOI. In 14 patients, biventricular activation times (by electrocardiographic imaging, ECGI) were obtained during intrinsic rhythm and for each pacing configuration to validate the findings. Device battery longevity was estimated at the 45-day follow-up. Results: The SPP-FOI method achieved greater QRS shortening than MPP (-56±16 vs. -42±17 ms, P

16 pags. 6 figs., 1 tab., Purpose: As multifocal contact lenses (MCLs) expand as a solution for presbyopia correction, a better understanding of their optical and visual performance becomes essential. Also, providing subjects with the experience of multifocal vision before contact lens fitting becomes critical, both to systematically test different multifocal designs and to optimize selection in the clinic. In this study, we evaluated the ability of a simultaneous vision visual simulator (SimVis) to represent MCLs. Methods: Through focus (TF) optical and visual quality with a center-near aspheric MCL (low, medium and high near adds) were measured using a multichannel polychromatic Adaptive Optics visual simulator equipped with double-pass, SimVis (temporal multi-plexing), and psychophysical channels to allow measurements on-bench and in vivo. On bench TF optical quality of SimVis-simulated MCLs was obtained from double-pass (DP) images and images of an E-stimulus using artificial eyes. Ten presbyopic subjects were fitted with the MCL. Visual acuity (VA) and DP retinal images were measured TF in a 4.00 D range with the MCL on eye, and through SimVis simulations of the same MCLs on the same subjects. Results: TF optical (on bench and in vivo) and visual (in vivo) quality measurements captured the expected broadening of the curves with increasing add. Root mean square difference between real and SimVis-simulated lens was 0.031/0.025 (low add), 0.025/0.015 (medium add), 0.019/0.011 (high add), for TF DP and TF LogMAR VA, respectively. A shape similarity metric shows high statistical values (lag κ = 0), rho = 0.811/0.895 (low add), 0.792/0.944 (medium add), and 0.861/0.915 (high add) for TF DP/LogMAR VA, respectively. Conclusions: MCLs theoretically and effectively expand the depth of focus. A novel simulator, SimVis, captured the through-focus optical and visual performance of the MCL in most of the subjects. Visual simulators allow subjects to experience vision with multifocal lenses prior to testing them on-eye. Translational Relevance: Simultaneous visual simulators allow subjects to experience multifocal vision non-invasively. We demonstrated equivalency between real multifocal contact lenses and SimVis-simulated lenses. The results suggest that SimVis is a suitable technique to aid selection of presbyopic corrections in the contactology practice., Supported by the European Research Council (ERC-2011-AdC 294099) to SM; Spanish Government (FIS2017-84753R) to SM, and pre-doctoral fellowship (FPU16/01944) to SA; Collaborative agreement with Johnson & Johnson Vision, Inc., Research & Development, Jacksonville, FL, USA.

Background There are no clearly defined indications for pancreas-preserving duodenectomy. The present study aimed to analyze postoperative morbidity and the outcomes of patients undergoing pancreas-preserving duodenectomy. Methods Patients undergoing pancreas-preserving duodenectomy from April 2008 to May 2020 were included. We divided the series according to indication: scenario 1, primary duodenal tumors; scenario 2, tumors of another origin with duodenal involvement; and scenario 3, emergency duodenectomy. Results We included 35 patients. Total duodenectomy was performed in 1 patient of adenomatous duodenal polyposis, limited duodenectomy in 7, and third + fourth duodenal portion resection in 27. The indications for scenario 1 were gastrointestinal stromal tumor (n = 13), adenocarcinoma (n = 4), neuroendocrine tumor (n = 3), duodenal adenoma (n = 1), and adenomatous duodenal polyposis (n = 1); scenario 2: retroperitoneal desmoid tumor (n = 2), recurrence of liposarcoma (n = 2), retroperitoneal paraganglioma (n = 1), neuroendocrine tumor in pancreatic uncinate process (n = 1), and duodenal infiltration due to metastatic adenopathies of a germinal tumor with digestive hemorrhage (n = 1); and scenario 3: aortoenteric fistula (n = 3), duodenal trauma (n = 1), erosive duodenitis (n = 1), and biliopancreatic limb ischemia (n = 1). Severe complications (Clavien-Dindo ≥ IIIb) developed in 14% (5/35), and postoperative mortality was 3% (1/35). Conclusions Pancreas-preserving duodenectomy is useful in the management of primary duodenal tumors, and is a technical option for some tumors with duodenal infiltration or in emergency interventions.

BACKGROUND Delaying initiation of tacrolimus after liver transplantation (LT) is a potential renal-sparing strategy. We assessed safety and efficacy of delayed initiation of prolonged-release tacrolimus (PR-T) in de novo LT. MATERIAL AND METHODS This was a single-center, single-arm, prospective, 12-month observational study of hepatitis C virus-negative orthotopic LT patients. Immunosuppression included PR-T (initially 0.1 or 0.2 mg/kg/day) initiated on Day 3 post LT, basiliximab (20 mg) on post-transplantation Day 0 and Day 4, and intraoperative corticosteroids (500 mg). Patients received maintenance corticosteroids and mycophenolate mofetil (MMF) according to center protocol. MMF dose was adjusted according to thrombocyte count. The primary endpoint was the estimated glomerular filtration rate (eGFR) measured using the Modification of Diet in Renal Disease 4-variable formula at 12 months. Secondary endpoints included biopsy-confirmed acute rejection (BCAR) and dialysis requirement. Adverse events were recorded. RESULTS Sixty-nine patients (mean age 55.0 years) were included. Most patients started MMF on Day 1 (60.9%) or Day 2 (10.1%), and PR-T on Day 3 (55.1%) or Day 4 (29.0%). Mean tacrolimus trough levels (ng/mL) were: Day 7, 9.5±6.3; Day 10, 9.4±5.4; Month 1, 8.0±3.1; Month 3, 7.8±3.7; Month 6, 8.0±4.1; and Month 12, 7.2±3.1. Mean 12-month eGFR was 77.2±24.5 mL/min/1.73 m2; 72.5% of patients had eGFR >60 mL/min/1.73 m² at 12 months; 89.9% had no eGFR measurements

Aim: To determine the safety and efficacy of self-administered outpatient parenteral antibiotic treatment (S-OPAT) within a hospitalization-at-home (HaH) program to manage a urinary tract infection (UTI) in patients referred directly from a hospital ED.Materials and Methods: This was a retrospective study of UTI episodes in patients treated initially in the ED, who were subsequently enrolled in a HaH program to receive S-OPAT. Epidemiological, clinical, and microbiological data were recorded. Safety was evaluated by means of mortality and the occurrence of unexpected hospital returns (reason, intra-hospital death) during the domiciliary period. The efficacy was evaluated considering the healing rate and analysis of mortality and repeat hospital admissions because of the UTI recurrence during the first month after discharge.Results: A total of 268 episodes of UTI were analyzed; the mean age of patients was 59.3 years, and 53% were female. The Charlson index was 1.97. The most common types of UTI were acute pyelonephritis and urosepsis. In 61.4% of urine cultures, microbiological documentation was obtained. E. coli was the most commonly isolated microorganism. A total of 27 strains of multidrug resistant microorganisms (MRD) were recorded. The most commonly used antimicrobial drug was ceftriaxone. There was one reported death. Clinical complications that resulted in returning to hospital occurred in 3.4% of cases. The healing rate was 96.5%. During the month after discharge, 4.4% of patients required repeat admission because of the UTI recurrence.Conclusion: S-OPAT within a HaH program in patients with UTI who are referred directly from ED is safe and effective.

Acute myocardial ischemia is known to be a pathology with a high mortality worldwide. In the last decades, computational simulation has been a widely used tool to study the electrophysiological effects of ischemia. In this work, we present an up-to-date model of the effects of myocardial ischemia in the action potential which includes more ischemia-affected current alterations than any other previously published model. The model was used to simulate action potentials during a 10-minute period of dynamic ischemia, and the main biomarkers of the action potential were monitored, as well as the extracellular potassium elevation. The results agree with those obtained experimentally, suggesting that the model can be useful for 3D simulations of acute myocardial ischemia.

This paper describes a computational approach designed to study ventricular tachyarrhythmias arising from acute myocardial ischemia. Since these cardiac disorders can frequently lead to sudden cardiac death, understanding their mechanisms is key to improving their diagnosis and therapy. The use of computational simulations based on multiscale mathematical modeling has proved to be a powerful tool in unraveling the causes of this phenomenon. In the first part of this work, we reformulated a model of the ischemic human ventricular cell to simulate the features of the action potentials during acute ischemia. We then incorporated the model into an electrophysiologically-detailed three-dimensional virtual human heart, which was able to reproduce the typical ventricular tachyarrhythmias in the first 15 min of ischemia with rhythms resembling ventricular fibrillation. The results suggest that the extracellular potassium concentration and the presence of a wash-out subendocardial zone are key factors in the vulnerability of the ischemic myocardium to arrhythmias.

Background We have previously shown that meal ingestion induces cognitive perception (sensations) with a hedonic dimension (well-being) that depends on the characteristics of the meal and the appropriateness of the digestive response. The aim of the present study is to identify metabolomic biomarkers of the cognitive response to meal ingestion. Methods In 18 healthy subjects, the response to a test meal (Edanec, 1 kcal/mL) ingested until maximum satiation (50 mL/min) was assessed. Perception measurements and blood samples were taken before, at the end of the meal, and 20 min after ingestion. The cognitive response and the hedonic dimension were measured on 10 cm scales. Metabolomic analysis was performed using nuclear magnetic resonance (NMR) spectroscopy and values of triglycerides, insulin, peptide YY (PYY), and glucagon-like peptide-1 (GLP-1) were determined using conventional laboratory techniques. Key Results Ingestion up to maximum satiation induced sensation of fullness and decreased digestive well-being. The total amount ingested by each subject correlated with the basal sensation of hunger, but not with other sensations or blood metabolite levels. Immediately after ingestion, satiation correlated with an increase in glucose (R = 0.49; p = 0.038) and valine levels (R = 0.48; p = 0.043). Twenty-minutes after finalizing ingestion, triglyceride levels had significantly increased which correlated with the recovery in well-being (R = 0.48; p = 0.046) and the decrease in desire to eat a food of choice (R = −0.56; p = 0.016). The increase in lipids inversely correlated with abdominal discomfort (R = −0.51; p = 0.032). Conclusions & Inferences Cognitive and hedonic responses to meal ingestion correlate with changes in circulating metabolites, which may serve as objective biomarkers of perception.

Objective: The aim of the study was to investigate whether the accuracy of ultrasound estimates of fetal weight (EFW) was dependent on maternal obesity.Study design: A prospective cross-sectional s...

UP&DOWN Study Group additional members: Coordinator: Ascension Marcos; Principal Investigators: Ascension Marcos, Jose Castro-Piñero, Oscar L. Veiga, and Fernando Bandres; Scientific Coordinators: David Martinez-Gomez (chair), Jonatan R. Ruiz (co-chair), Ana Carbonell-Baeza, Sonia Gomez-Martinez, and Catalina Santiago; Spanish National Research Council: Ascension Marcos, Sonia Gomez-Martinez, Esther Nova, Ligia-Esperanza Diaz, Belen Zapatera, Ana M. Veses, Aurora Hernandez, and Alina Gheorghe; University of Cadiz: José Castro-Piñero, Jesus Mora-Vicente, Jose L. Gonzalez-Montesinos, Julio Conde-Caveda, Jonatan R. Ruiz (University of Granada [UGR]), Francisco B. Ortega (UGR), Carmen Padilla Moledo, Ana Carbonell Baeza, Palma Chillon (UGR), Jorge del Rosario Fernandez, Ana Gonzalez Galo, Gonzalo Bellvis Guerra, Alvaro Delgado Alfonso, Fernando Parrilla, Roque Gomez, and Juan Gavala; Autonomous University of Madrid: Oscar L. Veiga, H. Ariel Villagra, Juan del-Campo, Carlos Cordente (UPM), Mario Diaz, Carlos M. Tejero, Aitor Acha, Jose M. Moya, Alberto Sanz, David Martinez-Gomez, Veronica Cabanas-Sanchez, Gabriel RodriguezRomo (UPM), Rocio Izquierdo, Laura Garcia-Cervantes, and Irene Esteban-Cornejo; Complutense University of Madrid: Fernando Bandres, Alejandro Lucia (European University of Madrid [UEM]), Catalina Santiago (UEM), and Felix Gomez-Gallego (UEM)., [Objectives]: To study the cross-sectional and longitudinal (2-year follow-up) association between muscle fitness and cardiovascular disease (CVD) risk factors in youth; whether there are muscle fitness cut points associated with CVD risk (cross-sectional); and whether the health-related muscle fitness cut points identified at baseline are associated with CVD risk 2 years later. [Study design]: In total, 237 children (110 girls) aged 6-10 years and 274 adolescents (131 girls) aged 12-16 years with complete data were included in the study (10.3% drop out). The handgrip strength and the standing long jump tests were used to assess muscle fitness. CVD risk score was computed with sum of 2 skinfolds, systolic blood pressure, insulin, glucose, triglycerides, and total cholesterol/high density lipoprotein cholesterol. [Results]: Muscle fitness at baseline was associated inversely with single CVD risk factors and CVD risk score at baseline and 2-year follow-up (all P, Supported by the DEP 2010-21662-C04-00 (DEP 2010-21662-C04-01: DEP 2010-21662-C04-02: DEP 2010-21662-C04-03: DEP 2010-21662-C04-04) grant from the National Plan for Research, Development and Innovation (R + D + i) MICINN, by the FPU15/05337 grant from the Spanish Ministry of Education, and by Plan Propio de Investigación 2016 of the University of Granada (Spain), Excellence actions: Units of Excellence; Scientific Unit of Excellence on Exercise and Health (UCEES).

The goal of FOCUS, which stands for Frailty Management Optimization through EIPAHA Commitments and Utilization of Stakeholders’ Input , is to reduce the burden of frailty in Europe. The partners are working on advancing knowledge of frailty detection, assessment, and management, including biological, clinical, cognitive and psychosocial markers, in order to change the paradigm of frailty care from acute intervention to prevention. FOCUS partners are working on ways to integrate the best available evidence from frailty-related screening tools, epidemiological and interventional studies into the care of frail people and their quality of life. Frail citizens in Italy, Poland and the UK and their caregivers are being called to express their views and their experiences with treatments and interventions aimed at improving quality of life. The FOCUS Consortium is developing pathways to leverage the knowledge available and to put it in the service of frail citizens. In order to reach out to the broadest audience possible, the FOCUS Platform for Knowledge Exchange and the platform for Scaling Up are being developed with the collaboration of stakeholders. The FOCUS project is a development of the work being done by the European Innovation Partnership on Active and Healthy Ageing (EIPAHA), which aims to increase the average healthy lifespan in Europe by 2020 while fostering sustainability of health/social care systems and innovation in Europe. The knowledge and tools developed by the FOCUS project, with input from stakeholders, will be deployed to all EIPAHA participants dealing with frail older citizens to support activities and optimize performance.

While improved surgical techniques, post-operative care, and immunosuppression regimens have reduced morbidity and mortality associated with orthotopic liver transplantation (OLT), further improvement of outcomes requires personalized treatment and a better understanding of genomic mechanisms involved. Gene expression profiles of ischemia/reperfusion (I/R) injury, regeneration, and rejection, may suggest mechanisms for development of better predictive tools and treatments. The liver is unique in its regenerative potential, recovering lost mass and function after injury from ischemia, resection, and rejection. I/R injury, an inevitable consequence of perfusion cessation, cold storage, and reperfusion, is regulated by the interaction of the immune system, inflammatory cytokines, and reduced microcirculatory blood flow in the liver. Rejection, a common post-operative complication, is mediated by the recipient's immune system through T-cell-dependent responses activating proinflammatory and apoptotic pathways. Characterizing distinctive gene expression signatures for these events can identify therapies to reduce injury, promote regeneration, and improve outcomes. While certain markers of liver injury and regeneration have been observed in animals, many of these are unverified in human studies. Further investigation of these genomic signatures and mechanisms through new technology offers promise, but continues to pose a significant challenge. An overview of the current fund of knowledge in this area is reviewed.

Purpose This study investigated factors associated with persistent serous retinal detachment in highly myopic eyes with vertical oval-shaped domes. Methods Twenty-eight highly myopic patients (40 eyes) with smooth macular elevations related to a vertical oval-shaped dome were recruited. Serous retinal detachment was investigated; 11 eyes had persistent submacular fluid (study group) and 29 eyes lacked submacular fluid (control group). All patients underwent complete ophthalmologic examinations, including axial-length measurement and fluorescein angiography. Spectral domain optical coherence tomography scans through the fovea measured choroidal thicknesses, macular bulge height, and vitreoretinal interface factors. Results No studied variables (age, sex, spherical equivalence, axial length, vitreomacular traction, epiretinal membrane, and internal limiting membrane detachment) except higher macular bulge height (P = 0.03) and a reduced macular choroidal thickness (P = 0.02) were associated with the risk of serous retinal detachment. No statistically significant differences in best-corrected visual acuity were observed between the study and control groups. Serous retinal detachment always occurred at the top of the inward incurvation of the macula and was characterized by multiple hyperfluorescent granular patches on fluorescein angiography. Conclusion A higher macular bulge height and a reduced macular choroidal thickness might be important factors in the development of serous retinal detachment in patients with vertical oval-shaped domes.