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(1) Background: The global coronavirus disease 2019 vaccination adapts to protect populations from emerging variants. This communication presents interim findings from the new Omicron XBB.1.16-adapted PHH-1V81 protein-based vaccine compared to an XBB.1.5-adapted mRNA vaccine against various acute respiratory syndrome coronavirus 2 (SARS-CoV-2) strains. (2) Methods: In a Phase IIb/III pivotal trial, adults previously vaccinated with a primary scheme and at least one booster dose of an EU-approved mRNA vaccine randomly received either the PHH-1V81 or BNT162b2 XBB.1.5 vaccine booster as a single dose. The primary efficacy endpoint assessed neutralization titers against the Omicron XBB.1.16 variant at day 14. Secondary endpoints evaluated neutralization titers and cellular immunity against different variants. Safety endpoints comprised solicited reactions up to day 7 post-vaccination and serious adverse events until the cut-off date of the interim analysis. Changes in humoral responses were assessed by pseudovirion-based or virus neutralization assays. (3) Results: At the cut-off date, immunogenicity assessments included 599 participants. Both boosters elicited neutralizing antibodies against XBB.1.16, XBB.1.5, and JN.1, with PHH-1V81 inducing a higher response for all variants. The PHH-1V8 booster triggers a superior neutralizing antibody response against XBB variants compared to the mRNA vaccine. A subgroup analysis consistently revealed higher neutralizing antibody responses with PHH-1V81 across age groups, SARS-CoV-2 infection history, and the number of prior vaccination shots. A safety analysis (n = 607) at the day 14 visit revealed favorable safety profiles without any serious vaccine-related adverse events. (4) Conclusions: PHH-1V81 demonstrates superiority on humoral immunogenicity compared to the mRNA vaccine against XBB variants and non-inferiority against JN.1 with a favorable safety profile and lower reactogenicity, confirming its potential as a vaccine candidate.

Introduction and Objectives: There is limited evidence regarding the use of subcutaneous implantable cardioverter-defibrillators (S-ICD) in pediatric patients. The aim of this study was to determine the incidence of complications in these patients at our center, according to the type of ICD and patient size., Methods: We included all patients aged<18 years who received an S-ICD since 2016 at our center. As a control group, we also included contemporary patients (since 2014) who received a transvenous ICD (TV-ICD). The primary endpoint was a composite of complications and inappropriate shocks., Results: A total of 26 patients received an S-ICD (median age, 14 [5-17] years; body mass index [BMI], 20.2 kg/m 2 ). Implantation was intermuscular in 23 patients (88%) and subserratus in the remainder. Two incisions were used in 24 patients (92%). In all patients, 2 zones were programmed: a conditional zone set at 230 (220-230) bpm, and a shock zone set at 250 bpm. Nineteen patients received a TV-ICD (median age, 11 [range, 5-16] years; BMI, 19.2 kg/m 2 , 79% single-chamber). Survival free from the primary endpoint at 5 years was 80% in the S-ICD group and 63% in the TV-ICD group (P=.54). Survival free from inappropriate shocks was similar (85% vs 89%, P=.86), while survival free from complications was higher in the S-ICD group (96% vs 57%, cloglog P=.016). There were no therapy failures in the S-ICD group, and no increased complication rates were observed in patients with BMI ≤20 kg/m 2 ., Conclusions: With contemporary implantation techniques and programming, S-ICD is a safe and effective therapy in pediatric patients. The number of inappropriate shocks is similar to TV-ICD, with fewer short- and mid-term complications., (Copyright © 2023. Published by Elsevier España, S.L.U.)

Aims: A cross-sectional study was carried out to assess the seroprevalence and risk factors associated with Trichinella spp. exposure in wild boar and Iberian domestic pigs from Mediterranean ecosystems of southwestern Spain., Methods and Results: Serum samples from 1360 wild boar and 439 Iberian domestic pigs were obtained during 2015-2020, from regions where Iberian pigs are raised under extensive conditions, hence sharing habitat with wild boar. Seropositivity was found in 7.4% (100/1360; 95% CI: 6.1-8.9) of the wild boar analysed. In this species, the individual seroprevalence ranged from 3.6% (8/223) (hunting season 2016-2017) to 11.4% (37/326) (2018-2019). A significant higher seropositivity was observed during the hunting season 2018-2019 (p < 0.009: OR = 3.07; 95% CI = 1.32-7.18) and one statistically significant cluster was detected within the studied area, in south central Andalusia [Relative Risk (RR) = 2.9; p = 0.037]. Females showed a significantly higher seroprevalence than males (8.7% vs. 5.8%) (p < 0.001: OR = 1.58; 95% CI = 1.08-2.32). No seropositivity to Trichinella spp. was detected in Iberian domestic pigs (0.0%; 95% CI: 0.0-0.9)., Conclusions: Although wild boar play an important role as a reservoir of Trichinella sp. in the Mediterranean ecosystems of southwestern Spain, our results suggest that the wild boar production system does not seem to pose a risk of Trichinella exposure to domestic pigs, despite sharing habitats in these ecosystems., (© 2023 The Authors. Zoonoses and Public Health published by Wiley-VCH GmbH.)

Background: A SARS-CoV-2 protein-based heterodimer vaccine, PHH-1V, has been shown to be safe and well-tolerated in healthy young adults in a first-in-human, Phase I/IIa study dose-escalation trial. Here, we report the interim results of the Phase IIb HH-2, where the immunogenicity and safety of a heterologous booster with PHH-1V is assessed versus a homologous booster with BNT162b2 at 14, 28 and 98 days after vaccine administration., Methods: The HH-2 study is an ongoing multicentre, randomised, active-controlled, double-blind, non-inferiority Phase IIb trial, where participants 18 years or older who had received two doses of BNT162b2 were randomly assigned in a 2:1 ratio to receive a booster dose of vaccine-either heterologous (PHH-1V group) or homologous (BNT162b2 group)-in 10 centres in Spain. Eligible subjects were allocated to treatment stratified by age group (18-64 versus ≥65 years) with approximately 10% of the sample enrolled in the older age group. The primary endpoints were humoral immunogenicity measured by changes in levels of neutralizing antibodies (PBNA) against the ancestral Wuhan-Hu-1 strain after the PHH-1V or the BNT162b2 boost, and the safety and tolerability of PHH-1V as a boost. The secondary endpoints were to compare changes in levels of neutralizing antibodies against different variants of SARS-CoV-2 and the T-cell responses towards the SARS-CoV-2 spike glycoprotein peptides. The exploratory endpoint was to assess the number of subjects with SARS-CoV-2 infections ≥14 days after PHH-1V booster. This study is ongoing and is registered with ClinicalTrials.gov, NCT05142553., Findings: From 15 November 2021, 782 adults were randomly assigned to PHH-1V (n = 522) or BNT162b2 (n = 260) boost vaccine groups. The geometric mean titre (GMT) ratio of neutralizing antibodies on days 14, 28 and 98, shown as BNT162b2 active control versus PHH-1V, was, respectively, 1.68 (p < 0.0001), 1.31 (p = 0.0007) and 0.86 (p = 0.40) for the ancestral Wuhan-Hu-1 strain; 0.62 (p < 0.0001), 0.65 (p < 0.0001) and 0.56 (p = 0.003) for the Beta variant; 1.01 (p = 0.92), 0.88 (p = 0.11) and 0.52 (p = 0.0003) for the Delta variant; and 0.59 (p ≤ 0.0001), 0.66 (p < 0.0001) and 0.57 (p = 0.0028) for the Omicron BA.1 variant. Additionally, PHH-1V as a booster dose induced a significant increase of CD4 + and CD8 + T-cells expressing IFN-γ on day 14. There were 458 participants who experienced at least one adverse event (89.3%) in the PHH-1V and 238 (94.4%) in the BNT162b2 group. The most frequent adverse events were injection site pain (79.7% and 89.3%), fatigue (27.5% and 42.1%) and headache (31.2 and 40.1%) for the PHH-1V and the BNT162b2 groups, respectively. A total of 52 COVID-19 cases occurred from day 14 post-vaccination (10.14%) for the PHH-1V group and 30 (11.90%) for the BNT162b2 group (p = 0.45), and none of the subjects developed severe COVID-19., Interpretation: Our interim results from the Phase IIb HH-2 trial show that PHH-1V as a heterologous booster vaccine, when compared to BNT162b2, although it does not reach a non-inferior neutralizing antibody response against the Wuhan-Hu-1 strain at days 14 and 28 after vaccination, it does so at day 98. PHH-1V as a heterologous booster elicits a superior neutralizing antibody response against the previous circulating Beta and the currently circulating Omicron BA.1 SARS-CoV-2 variants in all time points assessed, and for the Delta variant on day 98 as well. Moreover, the PHH-1V boost also induces a strong and balanced T-cell response. Concerning the safety profile, subjects in the PHH-1V group report significantly fewer adverse events than those in the BNT162b2 group, most of mild intensity, and both vaccine groups present comparable COVID-19 breakthrough cases, none of them severe., Funding: HIPRA SCIENTIFIC, S.L.U., Competing Interests: The authors of this manuscript declare: J Blanco has received institutional grants from HIPRA, 10.13039/501100016387Grifols, and MSD, royalties for licensed patent from AlbaJuna, honoraria for lectures from FLS Science and CIBER, supporting for meeting and/or travel from 10.13039/100016016Gilead Sciences, and unpaid independent COVID-19 monitoring from GMCSC (Multidisciplinary Collaborative Group for the Scientific Monitoring of COVID-19) and unpaid participation in COVID-19 advisory group for CCAC (Comitè Científic Assessor de la COVID-19). Outside of this work, J Blanco is the CEO, founder and shareholder of AlbaJuna Therapeutics, S.L. J Corominas, C Garriga, A Barreiro, L González-González, L Madrenas, I Güell, D Raïch-Regué, J G Prado, T Prat, E Torroella, B Trinité, L Ferrer, M Cañete and A Prenafeta have received funding from HIPRA. The funding from HIPRA to R Ramos was paid to his institution. A Soriano has received grants from 10.13039/100004319Pfizer and 10.13039/100005564Gilead Sciences, consulting fees from 10.13039/100004319Pfizer, MSD and 10.13039/501100005612Shionogi, and honoraria for lectures for 10.13039/100004319Pfizer, MSD, 10.13039/100005564Gilead Sciences, 10.13039/501100005612Shionogi, 10.13039/501100006546Angelini, and Menarini. B Trinité declares royalties by an institutional agreement and consulting fees for HIPRA, and is an unpaid member in advisory board for the Health Department of the 10.13039/501100002809Generalitat de Catalunya. N Izquierdo-Useros, D Raïch-Regué and M Gallemí declare institutional grants from HIPRA, Pharma Mar, 10.13039/501100016387Grifols, Dentaid, Palobiofarma, Mynorix and Amassence. N Izquierdo-Useros and M Gallemí have received speaking honoraria from FLS Science. JR Arribas has received consulting fees and payment for participating in advisory board from 10.13039/100005564Gilead Sciences, MSD, GSK, Eli Lilly, 10.13039/100004337Roche, 10.13039/100004319Pfizer and Sobi, honoraria for lectures and support for meetings and/or travel from MSD. A Borobia has received grants from GSK, Moderna and Janssen, speaking honoraria for Janssen, 10.13039/100005564Gilead Sciences and 10.13039/100004319Pfizer, and payment for participating in advisory board for 10.13039/100004319Pfizer, Janssen and MDI. PM García has received consulting fees and speaking honoraria from 10.13039/100005564Gilead Sciences, Mundipharma and 10.13039/100004319Pfizer, payment for expert testimony and participated in advisory board for 10.13039/100005564Gilead Sciences and received support for meeting and/or travel from 10.13039/100004319Pfizer. S Otero-Romero has received speaking honoraria from Genzyme, Biogen-Idec, Novartis, Roche, and MSD. Julia G Prado declares institutional grants from 10.13039/501100016387Grifols. J Corominas, C Garriga, A Prenafeta, A Moros, M Cañete, A Barreiro, L González-González, L Madrenas, I Güell, T Prat, E Torroella and L Ferrer are employees of HIPRA. Some of these authors may have stocks of HIPRA. Several patent applications have been filed by HIPRA SCIENTIFIC S.L.U. and Laboratorios HIPRA, S.A. on different SARS-CoV-2 vaccine candidates and SARS-CoV-2 subunit vaccines, including the novel recombinant RBD fusion heterodimer PHH-1V. A Barreiro, J Corominas, A Prenafeta, L González-González, L Madrenas, L Ferrer, E Torroella, T Prat and C Garriga are the inventors of these patent applications. N Izquierdo-Useros is a patent inventor with no economical compensation for Pharma Mar and Mynorix. The other authors have no relevant conflicts of interest to declare., (© 2023 The Author(s).)

Background: The frequency and clinical presentation of malaria infections show marked heterogeneity in epidemiological studies. However, deeper understanding of this variability is hampered by the difficulty in quantifying all relevant factors. Here, we report the history of malaria infections in twins, who are exposed to the same in utero milieu, share genetic factors, and are similarly exposed to vectors., Methods: Data were obtained from a Malian longitudinal birth cohort. Samples from 25 twin pairs were examined for malaria infection and antibody responses. Bayesian models were developed for the number of infections during follow-up., Results: In 16 of 25 pairs, both children were infected and often developed symptoms. In 8 of 25 pairs, only 1 twin was infected, but usually only once or twice. Statistical models suggest that this pattern is not inconsistent with twin siblings having the same underlying infection rate. In a pair with discordant hemoglobin genotype, parasite densities were consistently lower in the child with hemoglobin AS, but antibody levels were similar., Conclusions: By using a novel design, we describe residual variation in malaria phenotypes in naturally matched children and confirm the important role of environmental factors, as suggested by the between-twin pair heterogeneity in malaria history., Competing Interests: Potential conflicts of interest. All authors: No reported conflicts. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed., (Published by Oxford University Press on behalf of Infectious Diseases Society of America 2022.)

Due to their suppressive capacity, the adoptive transfer of regulatory T cells (Treg) has acquired a growing interest in controlling exacerbated inflammatory responses. Limited Treg recovery and reduced quality remain the main obstacles in most current protocols where differentiated Treg are obtained from adult peripheral blood. An alternate Treg source is umbilical cord blood, a promising source of Treg cells due to the higher frequency of naïve Treg and lower frequency of memory T cells present in the fetus' blood. However, the Treg number isolated from cord blood remains limiting. Human thymuses routinely discarded during pediatric cardiac surgeries to access the retrosternal operative field has been recently proposed as a novel source of Treg for cellular therapy. This strategy overcomes the main limitations of current Treg sources, allowing the obtention of very high numbers of undifferentiated Treg. We have developed a novel good manufacturing practice (GMP) protocol to obtain large Treg amounts, with very high purity and suppressive capacity, from the pediatric thymus (named hereafter thyTreg). The total amount of thyTreg obtained at the end of the procedure, after a short-term culture of 7 days, reach an average of 1,757 x10 6 (range 50 x 10 6 - 13,649 x 10 6 ) cells from a single thymus. The thyTreg product obtained with our protocol shows very high viability (mean 93.25%; range 83.35% - 97.97%), very high purity (mean 92.89%; range 70.10% - 98.41% of CD25 + FOXP3 + cells), stability under proinflammatory conditions and a very high suppressive capacity (inhibiting in more than 75% the proliferation of activated CD4 + and CD8 + T cells in vitro at a thyTreg:responder cells ratio of 1:1). Our thyTreg product has been approved by the Spanish Drug Agency (AEMPS) to be administered as cell therapy. We are recruiting patients in the first-in-human phase I/II clinical trial worldwide that evaluates the safety, feasibility, and efficacy of autologous thyTreg administration in children undergoing heart transplantation (NCT04924491). The high quality and amount of thyTreg and the differential features of the final product obtained with our protocol allow preparing hundreds of doses from a single thymus with improved therapeutic properties, which can be cryopreserved and could open the possibility of an "off-the-shelf" allogeneic use in another individual., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Bernaldo-de-Quirós, Cózar, López-Esteban, Clemente, Gil-Jaurena, Pardo, Pita, Pérez-Caballero, Camino, Gil, Fernández-Santos, Suarez, Pion, Martínez-Bonet and Correa-Rocha.)

Continuous incisional lidocaine infusion has been proposed as an adjunctive therapy in the management of postoperative pain in adult patients. The aim of this study was to determine the efficacy and safety of a continuous subcutaneous lidocaine infusion in pediatric patients following open heart surgery. All patients receiving a subcutaneous lidocaine infusion in median sternotomy incisions after open heart surgery during 2 consecutive years were included in the study. A historical cohort of patients was used as a control group. Demographic variables (age, size, and surgical procedure), variables related to sedation and analgesia (COMFORT and analgesia scales, drug doses, and duration), and complications were registered. 106 patients in the lidocaine infusion group and 79 patients in the control group were included. Incisional analgesia was effective for the treatment of pain as it reduced the dose and duration of intravenous fentanyl (odds ratio (OR) 6.26, confidence interval (CI) 95%: 2.48-15.97, p = 0.001; OR 4.30, CI 95%: 2.09-8.84, p = 0.001, respectively). The reduction in fentanyl use was more important in children over two years of age. Adverse effects were seen in three children (2.8%): they all had decreased level of consciousness, and one of them presented seizures as well. Two of these three patients had lidocaine levels over 2 mcg/ml. A continuous lidocaine incisional infusion is effective for the treatment of pain after open heart surgery. This procedure reduced intravenous analgesic drug requirements in pediatric patients undergoing a median sternotomy incision. Although the incidence of secondary effects is low, monitoring of neurologic status and lidocaine blood levels are recommended in all patients., Competing Interests: The authors declare that there are no conflicts of interest regarding the publication of this paper., (Copyright © 2022 Sarah Nicole Fernández et al.)

Fasciolosis is an important economic disease of livestock. There is a global interest in the development of protective vaccines since current anthelmintic therapy is no longer sustainable. A better knowledge of the host-parasite interaction is needed for the design of effective vaccines. The present study evaluates the microscopical hepatic lesions in sheep immunized with a partially protective vaccine (VAC1), a non-protective vaccine (VAC2), and an infected control group (IC). The nature of granulomatous inflammation associated with degeneration of adult flukes found in the VAC1 group was characterized by immunohistochemistry. Hepatic lesions (fibrous perihepatitis, chronic tracts, bile duct hyperplasia, infiltration of eosinophils and lymphocytes and plasma cells) were significantly less severe in the VAC1 group than in the IC group. Dead adult flukes within bile ducts were observed only in the VAC1 group and were surrounded by a severe granulomatous inflammation composed by macrophages and multinucleate giant cells with a high expression of lysozyme, CD163 and S100 markers, and a low expression of CD68. Numerous CD3+ T lymphocytes and scarce infiltrate of FoxP3+ Treg and CD208+ dendritic cells were present. This is the first report describing degenerated flukes associated to a severe granulomatous inflammation in bile ducts in a F. hepatica vaccine trial.

Background: Collaboration between cardiac surgeons and cardiologists can offer interventions that each specialist may not be able to offer on their own. This type of collaboration has been demonstrated with the hybrid Stage I in patients with hypoplastic heart syndrome. Since that time, a hybrid approach to cardiac interventions has been expanded to an incredible variety of potential indications. Methods: Seventy-one patients were scheduled for a hybrid procedure along 8 years. This was defined as close collaboration between surgeon and cardiologist working together in the same room, either cath-lab (27 patients) or theater (44 patients). Results: Six groups were arbitrarily defined. A: vascular cut-down in the cath-lab (27 neonates); B: bilateral banding (plus ductal stent) in hypoplastic left heart syndrome or alike (15 children); C: perventricular closure of muscular ventricular septal defect (10 cases); D: balloon/stenting of pulmonary branches along with major surgical procedure (12 kids); E: surgical implantation of Melody valve (six patients) and others (F, one case). Two complications were recorded: left ventricular free wall puncture and previous conduit tearing. Both drawbacks were successfully sort out under cardiopulmonary by-pass. Conclusion: Surgeon and cardiologist partnership can succeed where their isolated endeavors are not enough. Hybrid procedures keep on spreading, overcoming initial expectations. As a bridge to biventricular repair or transplant, bilateral banding plus ductal stent sounds interesting. Novel indications can be classified into different groups. Hybrid procedures are not complication-free., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Gil-Jaurena, Zunzunegui, Pérez-Caballero, Pita, Pardo, Calle, Murgoitio, Ballesteros, Rodríguez and Medrano.)

The immunomodulatory capacity of F. hepatica antigens is probably one of the main reasons for the development of a driven non-protective Th2 immune response. In this study, we analysed the cellular response of hepatic lymph node cells and CD4 + T cells in terms of proliferative response, efficiency of antigen presentation and cytokine production, to F. hepatica-derived molecules, at early and late stages of the infection. Thirty-one sheep were allocated into five groups and were slaughtered at 16 dpi and 23 wpi. In order to analyse antigen-specific response, the following F. hepatica recombinant molecules were used: rFhCL1, rFhCL2, rFhCL3, rFhCB1, rFhCB2, rFhCB3, rFhStf-1, rFhStf-2, rFhStf-3 and rFhKT1. A cell proliferation assay using hepatic lymph node cells and an antigen presentation cell assay using CD4 + T cells were performed. At 16 dpi, all molecules but rFhStf-2 and rFhKT1 elicited a significant cell proliferative response on hepatic lymph node cells of infected animals. At both early and late stage of the infection, antigen presentation of rFhCB3 and rFhCL2 resulted in higher stimulation index of CD4 + T cells which was IL-2 mediated, although no statistically significant when compared to uninfected animals. Significant cytokine production (IL-4, IL-10 and IFN-γ) was conditioned by the antigen-specific cell stimulation. No CD4 + T cell exhaustion was detected in infected sheep at the chronic stage of the infection. This study addressed antigen-specific response to F. hepatica-derived molecules that are involved in key aspects of the parasite survival within the host.

Regulatory T cells (Tregs), which are characterized by the expression of the transcription factor forkhead box P3 (FOXP3), are the main immune cells that induce tolerance and are regulators of immune homeostasis. Natural Treg cells (nTregs), described as CD4 + CD25 + FOXP3 + , are generated in the thymus via activation and cytokine signaling. Transforming growth factor beta type 1 (TGF-β1) is pivotal to the generation of the nTreg lineage, its maintenance in the thymus, and to generating induced Treg cells (iTregs) in the periphery or in vitro arising from conventional T cells (Tconvs). Here, we tested whether TGF-β1 treatment, associated with interleukin-2 (IL-2) and CD3/CD28 stimulation, could generate functional Treg-like cells from human thymocytes in vitro, as it does from Tconvs. Additionally, we genetically manipulated the cells for ectopic FOXP3 expression, along with the TGF-β1 treatment. We demonstrated that TGF-β1 and ectopic FOXP3, combined with IL-2 and through CD3/CD28 activation, transformed human thymocytes into cells that expressed high levels of Treg-associated markers. However, these cells also presented a lack of homogeneous suppressive function and an unstable proinflammatory cytokine profile. Therefore, thymocyte-derived cells, activated with the same stimuli as Tconvs, were not an appropriate alternative for inducing cells with a Treg-like phenotype and function.

Background: The integration of 3D printing technology in hospitals is evolving toward production models such as point-of-care manufacturing. This study aims to present the results of the integration of 3D printing technology in a manufacturing university hospital., Methods: Observational, descriptive, retrospective, and monocentric study of 907 instances of 3D printing from November 2015 to March 2020. Variables such as product type, utility, time, or manufacturing materials were analyzed., Results: Orthopedic Surgery and Traumatology, Oral and Maxillofacial Surgery, and Gynecology and Obstetrics are the medical specialties that have manufactured the largest number of processes. Working and printing time, as well as the amount of printing material, is different for different types of products and input data. The most common printing material was polylactic acid, although biocompatible resin was introduced to produce surgical guides. In addition, the hospital has worked on the co-design of custom-made implants with manufacturing companies and has also participated in tissue bio-printing projects., Conclusions: The integration of 3D printing in a university hospital allows identifying the conceptual evolution to "point-of-care manufacturing."

Introduction: Heart transplant after Fontan completion poses a unique surgical challenge. Twenty patients are presented, stressing the technical hints performed in the five anastomoses to match the graft in the recipient., Methods: Data are collected from 20 Fontan patients between 2013 and 2019. Age (13 years), weight (37 kg.), and time interval between Fontan and transplant (7 years) are presented as median. Extracardiac conduit (size 18/20) was implanted in 15 patients, whereas atrio-pulmonary connection was performed in 4 and lateral tunnel in 1. Six patients developed protein-losing enteropathy. Seventeen stents had been previously deployed., Results: The five anastomoses underwent some changes. Left atrium once, aorta 9 times, superior vena cava 7 times, pulmonary branches 15 times, and inferior vena cava 12 times. Follow-up was complete for a median of 42 months (range 6-84). Two patients died. ECMO was needed in six cases for pulmonary hypertension. Four patients had collateral vessels occluded in the cath lab, and stents were placed in superior vena cava (1) and aorta (1) post-transplant. Protein-losing enteropathy was resolved in five patients. Interestingly, one patient was on a systemic assist device before transplant (Levitronix) and right assistance (ECMO) afterwards., Conclusions: Transplant in Fontan patients is actually challenging. Hints in every of the five proposed anastomoses must be anticipated, including stents removal. Extra tissue from the donor (innominate vein, aortic arch, and pericardium) is strongly advisable. ECMO for right ventricular dysfunction was needed in nearly one-third of the cases. Overall results can match other transplant cohorts.

In this work we report the protection found in a vaccination trial performed in sheep with two different vaccines composed each one by a cocktail of antigens (rCL1, rPrx, rHDM and rLAP) formulated in two different adjuvants (Montanide ISA 61 VG (G1) and Alhydrogel ® (G2)). The parameters of protection tested were fluke burden, faecal egg count and evaluation of hepatic lesions. In vaccinated group 1 we found a significant decrease in fluke burden in comparison to both unimmunised and infected control group (37.2%; p = 0.002) and to vaccinated group 2 (Alhydrogel ® ) (27.08%; p = 0.016). The lower fluke burden found in G1 was accompanied by a decrease in egg output of 28.71% in comparison with the infected control group. Additionally, gross hepatic lesions found in vaccine 1 group showed a significant decrease (p = 0.03) in comparison with unimmunised-infected group. The serological study showed the highest level for both IgG1 and IgG2 in animals from group 1. All these data support the hypothesis of protection found in vaccine 1 group.

Background: Fasciolosis is one of the most important parasitic diseases of livestock. The need for better control strategies gave rise to the identification of various vaccine candidates. The recombinant form of a member of the cysteine protease family, cathepsin L1 of Fasciola hepatica (FhCL1) has been a vaccine target for the past few decades since it has been shown to behave as an immunodominant antigen. However, when FhCL1 was used as vaccine, it has been observed to elicit significant protection in some trials, whereas no protection was provided in others., Methods: In order to improve vaccine development strategy, we conducted a linear B-cell epitope mapping of FhCL1 in sheep vaccinated with FhCL1, FhHDM, FhLAP and FhPrx plus Montanide and with significant reduction of the fluke burden, sheep vaccinated with FhCL1, FhHDM, FhLAP and FhPrx plus aluminium hydroxide and with non-significant reduction of the fluke burden, and in unvaccinated-infected sheep., Results: Our study showed that the pattern and dynamic of peptide recognition varied noticeably between both vaccinated groups, and that the regions 55-63 and 77-84, which are within the propeptide, and regions 102-114 and 265-273 of FhCL1 were specifically recognised only by vaccinated sheep with significant reduction of the fluke burden. In addition, these animals also showed significant production of specific IgG2, whereas none was observed in vaccinated-Aluminium hydroxide and in infected control animals., Conclusions: We have identified 42 residues of FhCL1 that contributed to protective immunity against infection with F. hepatica in sheep. Our results provide indications in relation to key aspects of the immune response. Given the variable outcomes of vaccination trials conducted in ruminants to date, this study adds new insights to improve strategies of vaccine development.

Testosterone secretion may regulate the reproductive effort and the development of sexual traits, but it may also involve costs at the immunological and metabolic levels. However, the evidence for this trade-off in wild populations is scarce. Cortisol also plays an important role in mediating the reproductive and immune functions. In this study, we analyzed whether the endoparasite burden relates to hormonal levels (fecal testosterone and cortisol metabolites) and/or morphological sexual traits (size of the dark ventral patch, a trait that indicates reproductive effort in males) in male Iberian red deer. For this purpose, we sampled male red deer harvested during hunting actions in 2 types of populations in south western Spain that differed in structure, affecting the level of male-male competition for mates. We used coprological analyses to estimate the parasite burden mainly of gastrointestinal and bronchopulmonary nematodes and of protozoa, and assessed testosterone and cortisol metabolite levels from fecal pellets. We found a positive relationship of host parasitation with both testosterone levels and the size of the dark ventral patch, but these relationships depended on the intensity of male-male competition in the population, being only found under the high-competition scenario. These results are discussed under the hypothesis of the testosterone immunocompetence handicap, suggesting a cost at the immunological level, and, therefore, higher susceptibility to parasite infection in males that make a greater reproductive effort. However, this effect seems to be modulated by the social environment (male-male competition) that might lead to different optima in testosterone production and sexual trait development., (© 2020 International Society of Zoological Sciences, Institute of Zoology/Chinese Academy of Sciences and John Wiley & Sons Australia, Ltd.)

Pulmonary valve repair in an adolescent through upper ministernotomy is reported. Several tips to enhance proper display of the valve in the surgical field are depicted., (Copyright © 2019 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.)

This report describes a simple way to deal with time-consuming adhesions and cannula handling in patients with a paracorporeal assist device who are undergoing heart transplantation. By connecting the extrathoracic lines to the heart-lung machine, chest reentry becomes a straightforward issue., (Copyright © 2019 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.)

Background: The peritoneal cell populations (PCP) are thought to play a crucial role during the early immune response in Fasciola hepatica infection while newly excysted juveniles (NEJ) are migrating in the peritoneal cavity (PC) towards the liver. In this study, we aimed to determine the immunophenotypes of the PCP and to analyse the dynamics of the recruitment of the PCP during the early and late stage of the infection in sheep infected with F. hepatica., Methods: Thirty-seven sheep were divided into three groups: Group 1 (n = 20) and 2 (n = 10) were challenged with F. hepatica, Group 3 (n = 7) was not infected and remained as uninfected control (UC). After the slaughtering, peritoneal lavages were carried out to isolate peritoneal cell populations at 1, 3, 9 and 18 days post-infection (dpi) for Group 1 and at 14 weeks post-infection (wpi) for Group 2 and 3. Flow cytometry was conducted to assess the dynamics of peritoneal cavity cell populations., Results: TCD4 cells showed a significant decrease at 1 and 18 dpi when compared to UC; no statistical differences were detected for TCD8 and WC1 + γδ during the early stage of the infection with respect to the UC. CD14 cells exhibited a decreasing trend, with a significant decrease at 9 and 18 dpi when compared to the UC. The dynamics of MHCII and CD83 cells showed a similar increasing pattern from 3 to 18 dpi. During the chronic stage, both TCD4 and TCD8 cells showed no significant differences when compared to the UC, although a slight but statistically significant higher level of WC1 + γδ cells was observed. A lower percentage of antigen-presenting cells (APCs) was detected with respect to the UC., Conclusions: The recruitment of the lymphocytes subsets did not show a significant increase during the course of the infection and only WC1 + γδ cells displayed a significant increase at the chronic stage. For the CD14, a decreasing trend was observed during the early stage, which was statistically significant at the chronic stage of the infection. Peritoneal CD83 and MHCII cells developed an increasing trend during the early stage of infection, and showed a significant decrease at the late stage of the infection.

Objectives: Aortic arch repair has been shifted from deep hypothermia plus circulatory arrest to cerebral perfusion at tepid temperatures. A step forward is a simultaneous brain-coronary perfusion, allowing beating-heart arch surgery., Methods: A 'Y' cannula from the arterial line delivers oxygenated blood to brain and heart. The arch is repaired on a beating heart at 25°C. Intracardiac repair is performed after running cardioplegia through the root line. Fifty patients are classified into 3 groups: A, Norwood (8 neonates); B, aortic arch (14 children) and C, aortic arch plus intracardiac repair (28 patients). Associated anomalies in Group C are as follows: ventricular septal defect (10), arterial switch (5), atrial septal defect (4), cor triatriatum (3), aortic commissurotomy (2), comprehensive repair (2), ostium primum (1) and Yasui (1)., Results: The mean bypass time was 161 ± 54.44 (range 93-312) min. Mean brain-coronary perfusion was 37.26 ± 10.54 (18-60) min. Mean coronary ischaemia was 31 ± 32.40 (0-160) min. The heart was not arrested in Group B patients. Follow-up was complete for a mean of 30 (1-48) months. Four patients died in the postoperative period. Two required angioplasty for recoarctation., Conclusions: Selective brain-coronary perfusion is feasible and easy to switch to conventional cardioplegia delivery. Coronary ischaemia can be notably reduced and even 0 min in isolated arch surgery.

Background: The majority of vaccination studies against infection with F. hepatica in a natural host have been conducted at the late stage of the infection when the host's immune response is already immunomodulated by the parasite towards a Th2 non-protective response. This study was aimed at analysing the dynamic of the cell populations present in peritoneal liquid and the production of free radicals by the peritoneal leukocytes in infected and vaccinated sheep with recombinant cathepsin L1 of F. hepatica (rFhCL1) in early stages of the infection., Methods: Forty-five sheep were divided into three groups: Group 1 remained as negative control (n = 5), Group 2 (n = 20) was challenged with F. hepatica and Group 3 (n = 20) was vaccinated with rFhCL1 and challenged with F. hepatica. After the slaughtering, peritoneal lavages were carried out at 1, 3, 9 and 18 days post-infection (dpi) to isolate peritoneal cell populations. Flow cytometry was conducted to assess levels of hydrogen peroxide (H 2 O 2 ) and nitric oxide (NO)., Results: There was a significant increase in the total number of leukocytes at 9 and 18 dpi in infected and vaccinated groups. Production of H 2 O 2 was significantly increased in peritoneal granulocytes in both infected and vaccinated groups. Production of nitric oxide showed a significant rise in the granulocytes and monocytes/macrophages in infected and vaccinated sheep. The NO production by granulocytes at 3 and 9 dpi was significantly higher in the vaccinated than in the infected animals., Conclusions: Experimental infection induced an increase in the total number of leukocytes within the abdominal cavity at 9 and 18 dpi, being more noticeable in vaccinated animals. Production of H 2 O 2 occurred mainly in granulocytes of vaccinated and infected animals. Production of NO was incremented in vaccinated and non-vaccinated animals in all peritoneal cells. Vaccinated animals produced significant higher level of H 2 O 2 and NO than infected animals.

The expression of T regulatory cells (Foxp3), regulatory (interleukin [IL]-10 and transforming growth factor beta [TGF-β]) and proinflammatory (tumor necrosis factor alpha [TNF-α] and interleukin [IL]-1β) cytokines was quantified using real time polymerase chain reaction (qRT-PCR) in the liver of sheep during early stages of infection with Fasciola hepatica (1, 3, 9, and 18 days post-infection [dpi]). Portal fibrosis was also evaluated by Masson's trichrome stain as well as the number of Foxp3 + cells by immunohistochemistry. Animals were divided into three groups: (a) group 1 was immunized with recombinant cathepsin L1 from F. hepatica (FhCL1) in Montanide adjuvant and infected; (b) group 2 was uniquely infected with F. hepatica; and (c) group 3 was the control group, unimmunized and uninfected. An overexpression of regulatory cytokines of groups 1 and 2 was found in all time points tested in comparison with group 3, particularly at 18 dpi. A significant increase of the number of Foxp3 + lymphocytes in groups 1 and 2 was found at 9 and 18 dpi relative to group 3. A progressive increase in portal fibrosis was found in groups 1 and 2 in comparison with group 3. In this regard, group 1 showed smaller areas of fibrosis than group 2. There was a significant positive correlation between Foxp3 and IL-10 expression (by immunohistochemistry and qRT-PCR) just as between portal fibrosis and TGF-β gene expression. The expression of proinflammatory cytokines increased gradually during the experience. These findings suggest the induction of a regulatory phenotype by the parasite that would allow its survival at early stages of the disease when it is more vulnerable.