Immunogenicity of chimeric hemagglutinins delivered by an orf virus vector platform against swine influenza virus.

Orf virus (ORFV) is a large DNA virus that can harbor and efficiently deliver viral antigens in swine. Here we used ORFV as a vector platform to deliver chimeric hemagglutinins (HA) of Influenza A virus of swine (IAV-S). Vaccine development against IAV-S faces limitations posed by strain-specific immunity and the antigenic diversity of the IAV-S strains circulating in the field. A promising alternative aiming at re-directing immune responses on conserved epitopes of the stalk segment of the hemagglutinin (HA2) has recently emerged. Sequential immunization with chimeric HAs comprising the same stalk but distinct exotic head domains can potentially induce cross-reactive immune responses against conserved epitopes of the HA2 while breaking the immunodominance of the head domain (HA1). Here, we generated two recombinant ORFVs expressing chimeric HAs encoding the stalk region of a contemporary H1N1 IAV-S strain and exotic heads derived from either H6 or H8 subtypes, ORFVΔ121cH6/1 and ORFVΔ121cH8/1, respectively. The resulting recombinant viruses were able to express the heterologous protein in vitro. Further, the immunogenicity and cross-protection of these vaccine candidates were assessed in swine after sequential intramuscular immunization with OV-cH6/1 and OV-cH8/1, and subsequent challenge with divergent IAV-S strains. Humoral responses showed that vaccinated piglets presented increasing IgG responses in sera. Additionally, cross-reactive IgG and IgA antibody responses elicited by immunization were detected in sera and bronchoalveolar lavage (BAL), respectively, by ELISA against different viral clades and a diverse range of contemporary H1N1 IAV-S strains, indicating induction of humoral and mucosal immunity in vaccinated animals. Importantly, viral shedding was reduced in nasal swabs from vaccinated piglets after intranasal challenge with either Oh07 (gamma clade) or Ca09 (npdm clade) IAV-S strains. These results demonstrated the efficiency of ORFV-based vectors in delivering chimeric IAV-S HA-based vaccine candidates and underline the potential use of chimeric-HAs for prevention and control of influenza in swine.

Improving ECMO therapy: Monitoring oxygenator functionality and identifying key indicators, factors, and considerations for changeout.

INTRODUCTION: The optimal timing for extracorporeal membrane oxygenation (ECMO) circuit change-out is crucial for the successful management of patients with severe cardiopulmonary failure. This comprehensive review examines the various factors that influence the timing of oxygenator replacement in the ECMO circuit. By considering these factors, clinicians can make informed decisions to ensure timely and effective change-out, enhancing patient outcomes and optimizing the delivery of ECMO therapy. METHODOLOGY: A thorough search of relevant studies on ECMO circuits and oxygenator change-out was conducted using multiple scholarly databases and relevant keywords. Studies published between 2017 and 2023 were included, resulting in 40 studies that met the inclusion criteria. DISCUSSION: Thrombosis within the membrane oxygenator and its impact on dysfunction were identified as significant contributors, highlighting the importance of monitoring coagulation parameters and gas exchange. Several factors, including fibrinogen levels, pre and post-membrane blood gases, plasma-free hemoglobin, D-dimers, platelet function, flows and pressures, and anticoagulation strategy, were found to be important considerations when determining the need for an oxygenator or circuit change-out. The involvement of a multidisciplinary team and thorough preparation were also highlighted as crucial aspects of this process. CONCLUSION: In conclusion, managing circuit change-outs in ECMO therapy requires considering factors such as fibrinogen levels, blood gases, plasma-free hemoglobin, D-dimers, platelet function, flows, pressures, and anticoagulation strategy. Monitoring these parameters allows for early detection of issues, timely interventions, and optimized ECMO therapy. Standardized protocols, personalized anticoagulation approaches, and non-invasive monitoring techniques can improve the safety and effectiveness of circuit change-outs. Further research and collaboration are needed to advance ECMO management and enhance patient outcomes.

Advocating for an open communication culture in perfusion and cardiothoracic community: a call to action.

This article advocates for an open communication culture in the perfusion and cardiothoracic community to enhance patient safety during surgery. All team members, including nurses, anesthesiologists, and perfusionists, should actively contribute their insights. Empowering perfusionists to voice concerns without fear of repercussions is crucial. Involvement in debriefs, root cause analyses and data management systems aids continuous improvement. A robust speak-up culture prevents unsafe practices and elevates perfusion care standards, leading to better patient outcomes.

A multipurpose Extracorporeal Life Support Circuit: a concept for multiorgan transplant and circulatory support service Healthcare provider.

The demand for efficient and adaptable life support systems in the field of Extracorporeal Life Support (ECLS) is steadily increasing. To meet this growing need, there is a requirement for a versatile extracorporeal life support circuit that can be effectively applied in various medical scenarios, especially in tertiary hospitals where multiple ECLS services are utilized. These services include Extracorporeal Membrane Oxygenation (ECMO) for addressing respiratory or cardiac problems, Ventricular Assist Device (VAD) as a bridge to recovery or heart transplant, and Venovenous Bypass (VVB) for assisting liver transplantation. In light of this, we propose the creation of a multipurpose circuit that integrates multiple extracorporeal life support (ECLS) functions to cater to diverse medical needs. This innovative circuit not only offers cost-effectiveness and enhanced safety but also ensures optimal utilization, thereby revolutionizing the realm of life support technologies.

Tergitol Based Decellularization Protocol Improves the Prerequisites for Pulmonary Xenografts: Characterization and Biocompatibility Assessment.

Right ventricle outflow tract obstruction (RVOTO) is a congenital pathological condition that contributes to about 15% of congenital heart diseases. In most cases, the replacement of the right ventricle outflow in pediatric age requires subsequent pulmonary valve replacement in adulthood. The aim of this study was to investigate the extracellular matrix scaffold obtained by decellularization of the porcine pulmonary valve using a new detergent (Tergitol) instead of Triton X-100. The decellularized scaffold was evaluated for the integrity of its extracellular matrix (ECM) structure by testing for its biochemical and mechanical properties, and the cytotoxicity/cytocompatibility of decellularized tissue was assessed using bone marrow-derived mesenchymal stem cells. We concluded that Tergitol could remove the nuclear material efficiently while preserving the structural proteins of the matrix, but without an efficient removal of the alpha-gal antigenic epitope. Therefore, Tergitol can be used as an alternative detergent to replace the Triton X-100.

White-tailed deer (Odocoileus virginianus) may serve as a wildlife reservoir for nearly extinct SARS-CoV-2 variants of concern.

The spillover of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) from humans to white-tailed deer (WTD) and its ability to transmit from deer to deer raised concerns about the role of WTD in the epidemiology and ecology of the virus. Here, we present a comprehensive cross-sectional study assessing the prevalence, genetic diversity, and evolution of SARS-CoV-2 in WTD in the State of New York (NY). A total of 5,462 retropharyngeal lymph node samples collected from free-ranging hunter-harvested WTD during the hunting seasons of 2020 (Season 1, September to December 2020, n = 2,700) and 2021 (Season 2, September to December 2021, n = 2,762) were tested by SARS-CoV-2 real-time RT-PCR (rRT-PCR). SARS-CoV-2 RNA was detected in 17 samples (0.6%) from Season 1 and in 583 samples (21.1%) from Season 2. Hotspots of infection were identified in multiple confined geographic areas of NY. Sequence analysis of SARS-CoV-2 genomes from 164 samples demonstrated the presence of multiple SARS-CoV-2 lineages and the cocirculation of three major variants of concern (VOCs) (Alpha, Gamma, and Delta) in WTD. Our analysis suggests the occurrence of multiple spillover events (human to deer) of the Alpha and Delta lineages with subsequent deer-to-deer transmission and adaptation of the viruses. Detection of Alpha and Gamma variants in WTD long after their broad circulation in humans in NY suggests that WTD may serve as a wildlife reservoir for VOCs no longer circulating in humans. Thus, implementation of continuous surveillance programs to monitor SARS-CoV-2 dynamics in WTD is warranted, and measures to minimize virus transmission between humans and animals are urgently needed.

Network meta-analysis comparing blood cardioplegia, Del Nido cardioplegia and custodiol cardioplegia in minimally invasive cardiac surgery.

INTRODUCTION: Minimally invasive cardiac surgery has been evolving, with the intention of reducing surgical trauma, improve cosmesis and patient satisfaction. Single dose, crystalloid cardioplegia such as Del Nido cardioplegia and Custoidol solution have been increasingly used to reduce the interruption from repeating cardioplegia dosing to minimise the cardiopulmonary bypass and cross clamp time. However, the best cardioplegia for myocardial protection in adult minimally invasive cardiac surgery remains controversial. We aimed to conduct a meta-analysis to analyse the current evidence in the literature. METHOD: A systematic review and meta-analysis was performed following the updated 2020 PRISMA guideline. Articles published in the five major electronic databases up 1st of April 2021 were identified and reviewed. The primary outcome was in-hospital or 30-day mortality. Traditional pairwise and Bayesian network meta-analyses were conducted. RESULTS: Nine articles were included in this study. The use of Del Nido cardioplegia was associated with a lower volume of cardioplegia used (Del Nido vs Blood, 1105.62 mL+/-123.47 vs 2569.46 mL+/-1515.52, p<0.001), cardiopulmonary bypass (Del Nido vs Custoidol vs Blood: 91.67+/-14.78 vs 138.05 +/- 21.30 vs 119.38+/-26.91 minutes, p<0.001) and cross-clamp time (Del Nido vs Custoidol vs Blood: 74.99+/-18.55 vs 82.01 +/- 17.28 vs 93.66+/-8.88 minutes, p < 0.001). No differences were observed in the incidence of in-hospital/30-day mortality rate, new onset of atrial fibrillation and stroke. Ranking analysis showed the Custoidol solution has the highest probability to be the first ranked cardioplegia. CONCLUSION: No differences were found between blood and crystalloid cardioplegia in adult minimally invasive cardiac surgery in several clinical outcomes. The cardioplegia of choice in minimally invasive cardiac surgery remains the surgeons' decision and preference.

Comparable outcomes from long and short read random sequencing of total RNA for detection of pathogens in chicken respiratory samples.

Co-infections of avian species with different RNA viruses and pathogenic bacteria are often misdiagnosed or incompletely characterized using targeted diagnostic methods, which could affect the accurate management of clinical disease. A non-targeted sequencing approach with rapid and precise characterization of pathogens should help respiratory disease management by providing a comprehensive view of the causes of disease. Long-read portable sequencers have significant potential advantages over established short-read sequencers due to portability, speed, and lower cost. The applicability of short reads random sequencing for direct detection of pathogens in clinical poultry samples has been previously demonstrated. Here we demonstrate the feasibility of long read random sequencing approaches to identify disease agents in clinical samples. Experimental oropharyngeal swab samples (n = 12) from chickens infected with infectious bronchitis virus (IBV), avian influenza virus (AIV) and Mycoplasma synoviae (MS) and field-collected clinical oropharyngeal swab samples (n = 11) from Kenyan live bird markets previously testing positive for Newcastle disease virus (NDV) were randomly sequenced on the MinION platform and results validated by comparing to real time PCR and short read random sequencing in the Illumina MiSeq platform. In the swabs from experimental infections, each of three agents in every RT-qPCR-positive sample (Ct range 19-34) was detectable within 1 h on the MinION platform, except for AIV one agent in one sample (Ct = 36.21). Nine of 12 IBV-positive samples were assigned genotypes within 1 h, as were five of 11 AIV-positive samples. MinION relative abundances of the test agent (AIV, IBV and MS) were highly correlated with RT-qPCR Ct values (R range-0.82 to-0.98). In field-collected clinical swab samples, NDV (Ct range 12-37) was detected in all eleven samples within 1 h of MinION sequencing, with 10 of 11 samples accurately genotyped within 1 h. All NDV-positive field samples were found to be co-infected with one or more additional respiratory agents. These results demonstrate that MinION sequencing can provide rapid, and sensitive non-targeted detection and genetic characterization of co-existing respiratory pathogens in clinical samples with similar performance to the Illumina MiSeq.

Putative Novel Avian Paramyxovirus (AMPV) and Reidentification of APMV-2 and APMV-6 to the Species Level Based on Wild Bird Surveillance (United States, 2016-2018).

Avian paramyxoviruses (APMVs) (subfamily Avulavirinae) have been isolated from over 200 species of wild and domestic birds around the world. The International Committee on Taxonomy of Viruses (ICTV) currently defines 22 different APMV species, with Avian orthoavulavirus 1 (whose viruses are designated APMV-1) being the most frequently studied due to its economic burden to the poultry industry. Less is known about other APMV species, including limited knowledge on the genetic diversity in wild birds, and there is a paucity of public whole-genome sequences for APMV-2 to -22. The goal of this study was to use MinION sequencing to genetically characterize APMVs isolated from wild bird swab samples collected during 2016 to 2018 in the United States. Multiplexed MinION libraries were prepared using a random strand-switching approach using 37 egg-cultured, influenza-negative, hemagglutination-positive samples. Forty-one APMVs were detected, with 37 APMVs having complete polymerase coding sequences allowing for species identification using ICTV's current Paramyxoviridae phylogenetic methodology. APMV-1, -4, -6, and -8 viruses were classified, one putative novel species (Avian orthoavulavirus 23) was identified from viruses isolated in this study, two putative new APMV species (Avian metaavulavirus 24 and 27) were identified from viruses isolated in this study and from retrospective GenBank sequences, and two putative new APMV species (Avian metaavulavirus 25 and 26) were identified solely from retrospective GenBank sequences. Furthermore, coinfections of APMVs were identified in four samples. The potential limitations of the branch length being the only species identification criterion and the potential benefit of a group pairwise distance analysis are discussed. IMPORTANCE Most species of APMVs are understudied and/or underreported, and many species were incidentally identified from asymptomatic wild birds; however, the disease significance of APMVs in wild birds is not fully determined. The rapid rise in high-throughput sequencing coupled with avian influenza surveillance programs have identified 12 different APMV species in the last decade and have challenged the resolution of classical serological methods to identify new viral species. Currently, ICTV's only criterion for Paramyxoviridae species classification is the requirement of a branch length of >0.03 using a phylogenetic tree constructed from polymerase (L) amino acid sequences. The results from this study identify one new APMV species, propose four additional new APMV species, and highlight that the criterion may have insufficient resolution for APMV species demarcation and that refinement or expansion of this criterion may need to be established for Paramyxoviridae species identification.

A New Decellularization Protocol of Porcine Aortic Valves Using Tergitol to Characterize the Scaffold with the Biocompatibility Profile Using Human Bone Marrow Mesenchymal Stem Cells.

The most common aortic valve diseases in adults are stenosis due to calcification and regurgitation. In pediatric patients, aortic pathologies are less common. When a native valve is surgically replaced by a prosthetic one, it is necessary to consider that the latter has a limited durability. In particular, current bioprosthetic valves have to be replaced after approximately 10 years; mechanical prostheses are more durable but require the administration of permanent anticoagulant therapy. With regard to pediatric patients, both mechanical and biological prosthetic valves have to be replaced due to their inability to follow patients' growth. An alternative surgical substitute can be represented by the acellular porcine aortic valve that exhibits less immunogenic risk and a longer lifespan. In the present study, an efficient protocol for the removal of cells by using detergents, enzyme inhibitors, and hyper- and hypotonic shocks is reported. A new detergent (Tergitol) was applied to replace TX-100 with the aim to reduce toxicity and maximize ECM preservation. The structural integrity and efficient removal of cells and nuclear components were assessed by means of histology, immunofluorescence, and protein quantification; biomechanical properties were also checked by tensile tests. After decellularization, the acellular scaffold was sterilized with a standard protocol and repopulated with bone marrow mesenchymal stem cells to analyze its biocompatibility profile.

In search of optimal cardioplegia for minimally invasive valve surgery.

Cardioplegic solutions are used in cardiac surgery to achieve controlled cardiac arrest during operations, making surgery safer. Cardioplegia can either be blood or crystalloid based, with perceived pros and cons of each type. Whilst it is known that cardioplegia causes cardiac arrest, there is debate over which cardioplegic solution provides the highest degree of myocardial protection during arrest. Myocardial damage is measured post-operatively by biomarkers such as serum TnT, TnI or CK-MB. It is known that the outcomes of minimally invasive valve surgery are comparable to full sternotomy valve operations. Despite there being a wide diversity in use of different cardioplegic solutions across the world, this comprehensive literature review found no superiority of one cardioplegic solution over the other for myocardial protection during minimally invasive valve procedures.

A Novel Recombinant Newcastle Disease Vaccine Improves Post- In Ovo Vaccination Survival with Sustained Protection against Virulent Challenge.

In ovo vaccination has been employed by the poultry industry for over 20 years to control numerous avian diseases. Unfortunately, in ovo live vaccines against Newcastle disease have significant limitations, including high embryo mortality and the inability to induce full protection during the first two weeks of life. In this study, a recombinant live attenuated Newcastle disease virus vaccine containing the antisense sequence of chicken interleukin 4 (IL-4), rZJ1*L-IL4R, was used. The rZJ1*L-IL4R vaccine was administered in ovo to naïve specific pathogen free embryonated chicken eggs (ECEs) and evaluated against a homologous challenge. Controls included a live attenuated recombinant genotype VII vaccine based on the virus ZJ1 (rZJ1*L) backbone, the LaSota vaccine and diluent alone. In the first of two experiments, ECEs were vaccinated at 18 days of embryonation (DOE) with either 104.5 or 103.5 50% embryo infectious dose (EID50/egg) and chickens were challenged at 21 days post-hatch (DPH). In the second experiment, 103.5 EID50/egg of each vaccine was administered at 19 DOE, and chickens were challenged at 14 DPH. Chickens vaccinated with 103.5 EID50/egg of rZJ1*L-IL4R had hatch rates comparable to the group that received diluent alone, whereas other groups had significantly lower hatch rates. All vaccinated chickens survived challenge without displaying clinical disease, had protective hemagglutination inhibition titers, and shed comparable levels of challenge virus. The recombinant rZJ1*L-IL4R vaccine yielded lower post-vaccination mortality rates compared with the other in ovo NDV live vaccine candidates as well as provided strong protection post-challenge.

Femoral versus axillary cannulation in acute type A aortic dissections: A meta-analysis.

OBJECTIVE: There has been a growing interest in antegrade cannulation techniques in type A aortic dissection surgery. Axillary cannulation has previously been reported to provide better outcomes in terms of short-term mortality and neurological event. Consensus regarding the best cannulation strategy still remains controversial. METHOD: The MEDLINE and EMBASE databases were conducted up until October 3, 2020. Data regarding mortality, stroke, reoperation for bleeding and length of hospital stay, wound infection and cardiopulmonary bypass time were extracted and submitted to a meta-analysis using random-effects modelling and the I2 -test for heterogeneity. Fourteen retrospective observational studies were included, enrolling a total of 2621 patients. RESULTS: There were a total of 2621 patients (1327 axillary cannulation and 874 femoral cannulation). Axillary cannulation was associated with reduced short term mortality (pooled odds ratio [OR] = +0.42, 95% confidence interval [CI] = +0.25 to +0.70; p = .0009) compared to femoral cannulation. Axillary cannulation was also associated with a lower incidence of neurological events (pooled OR = +0.63, 95% CI = +0.42 to +0.94; p = .02). CONCLUSION: Our meta-analyses suggests that axillary cannulation has superior outcomes in terms of mortality and stroke following emergency surgery for type A aortic dissection. However, the lack of high quality randomized controlled trials does not make this recommendation generalisable to all units.

Newcastle Disease Virus Induced Pathologies Severely Affect the Exocrine and Endocrine Functions of the Pancreas in Chickens.

Newcastle disease virus (NDV) causes a highly contagious and devastating disease in poultry. ND causes heavy economic losses to the global poultry industry by decreasing the growth rate, decrease in egg production high morbidity and mortality. Although significant advances have been made in the vaccine development, outbreaks are reported in vaccinated birds. In this study, we report the damage caused by NDV infection in the pancreatic tissues of vaccinated and specific-pathogen-free chickens. The histopathological examination of the pancreas showed severe damage in the form of partial depletion of zymogen granules, acinar cell vacuolization, necrosis, apoptosis, congestion in the large and small vessels, sloughing of epithelial cells of the pancreatic duct, and mild perivascular edema. Increased plasma levels of corticosterone and somatostatin were observed in NDV-infected chicken at three- and five- days post infection (DPI). A slight decrease in the plasma concentrations of insulin was noticed at 5 DPI. Significant changes were not observed in the plasma levels of glucagon. Furthermore, NDV infection decreased the activity and mRNA expression of amylase, lipase, and trypsin from the pancreas. Taken together, our findings highlight that NDV induces extensive tissue damage in the pancreas, decreases the activity and expression of pancreatic enzymes, and increases plasma corticosterone and somatostatin. These findings provide new insights that a defective pancreas may be one of the reasons for decreased growth performance after NDV infection in chickens.

Minimally invasive (mini-thoracotomy) versus median sternotomy in redo mitral valve surgery: A meta-analysis of observational studies.

OBJECTIVE: Redo mitral valve surgery has traditionally been performed via a median sternotomy. It is often challenging and is associated with increased perioperative mortality. Advances in cardiac surgical techniques over the last two decades have led to an increase in the use of a minimally invasive approach via a right anterolateral mini-thoracotomy as opposed to a repeat median sternotomy. However, despite these advances, there is no general consensus on the best form of entry, and as of yet, there are no randomized controlled trials. We performed a meta-analysis of observational studies to aid in determining the best approach for redo mitral valve surgery. METHOD: The MEDLINE and EMBASE databases were conducted up until 1 June 2020. Data regarding mortality, stroke, reoperation for bleeding and length of hospital stay, wound infection and cardiopulmonary bypass time were extracted and submitted to a meta-analysis using random effects modelling and the I2-test for heterogeneity. Seven retrospective observational studies were included, enrolling a total of 1070 patients. RESULTS: There were a total of 1070 patients. Of these 364 had non-sternotomy approach compared with 707 patients who had median sternotomy. Further subgroup analysis revealed that 327 of the 364 patients had a mini-thoracotomy approach while the remaining 37 patients had a full thoracotomy approach. In-hospital mortality and length of stay were less in non-sternotomy group compared to median sternotomy group. There were no differences in stroke, CPB time and wound infections between the two groups. CONCLUSION: Redo mitral valve surgery can be performed safely with satisfactory outcomes via a mini-thoracotomy approach. This meta-analysis shows comparable results with reduced in-hospital mortality and hospital length of stay with a mini-thoracotomy approach.

Real-time, MinION-based, amplicon sequencing for lineage typing of infectious bronchitis virus from upper respiratory samples.

Infectious bronchitis (IB) causes significant economic losses in the global poultry industry. Control of IB is hindered by the genetic diversity of the causative agent, infectious bronchitis virus (IBV), which has led to the emergence of several serotypes that lack complete serologic cross-protection. Although serotyping requires immunologic characterization, genotyping is an efficient means to identify IBVs detected in samples. Sanger sequencing of the S1 subunit of the spike gene is currently used to genotype IBV; however, the universal S1 PCR was created to work from cultured IBV, and it is inefficient at detecting multiple viruses in a single sample. We describe herein a MinION-based, amplicon-based sequencing (AmpSeq) method that genetically categorized IBV from clinical samples, including samples with multiple IBVs. Total RNA was extracted from 15 tracheal scrapings and choanal cleft swab samples, randomly reverse transcribed, and PCR amplified using modified S1-targeted primers. Amplicons were barcoded to allow for pooling of samples, processed per manufacturer's instructions into a 1D MinION sequencing library, and then sequenced on the MinION. The AmpSeq method detected IBV in 13 of 14 IBV-positive samples. AmpSeq accurately detected and genotyped both IBV lineages in 3 of 5 samples containing 2 IBV lineages. Additionally, 1 sample contained 3 IBV lineages, and AmpSeq accurately detected 2 of the 3 lineages. Strain identification, including detection of different IBVs from the same lineage, was also possible with this AmpSeq method. Our results demonstrate the feasibility of using MinION-based AmpSeq for rapid and accurate identification and lineage typing of IBV from oral swab samples.

Concomitant cardiac surgery and liver transplantation: an alternative approach in patients with end stage liver failure?

BACKGROUND: The results of cardiac surgery in patients with end-stage-liver-disease (ESLD) are poor. Concomitant cardiac surgery and orthotopic liver transplantation (OLT) may be an alternative treatment strategy in these patients. METHODS: Between 2001 and 2018, eight patients underwent concomitant cardiac surgery and OLT (Conc_OLT) in our institution. We analyzed their preoperative, intraoperative and postoperative data and compared them to seven high risk patients with ESLD who underwent isolated cardiac surgery (Iso_Surg). RESULTS: The two groups were not significantly different in terms of gender and age (Conc_OLT: 5 males, 55 ± 15 years, Iso_Surg: 4 males, 60 ± 10 years). Causes for ESLD were primary biliary cirrhosis (Conc_OLT = 1, Iso_Surg = 1), alcoholism (Conc_OLT = 2, Iso_Surg = 2), viral hepatitis (Conc_OLT = 2, Iso_Surg = 2), cryptogenic (Conc_OLT = 2, Iso_Surg = 1), ischemic (Conc_OLT = 1) and hepatocellular carcinoma (Iso_Surg = 1). Model for End-stage-Liver-Disease (MELD) Score (Conc_OLT = 14, Iso_Surg = 13) and Child-Pugh Score (Conc_OLT = 9.5, Iso_Surg = 8) were not significantly different between the two groups. Median logistic European System for Cardiac Operative Risk Evaluation (EuroSCORE) was 9.5% (Conc_OLT) and 7.1% (Iso_Surg). Cardiac procedures undertaken were aortic valve replacement (Conc_OLT = 6, Iso_Surg = 3), coronary bypass grafting (Conc_OLT = 1,Iso_Surg = 2), tricuspid valve repair (Conc_OLT = 1), combined aortic and mitral valve replacement (Iso_Surg = 1) and excision of atrial myxoma (Iso_Surg = 1). Median length of in-hospital-stay was longer in the Conc_OLT group (73 vs. 42 days; p = 0.11). At 3 months, in-hospital mortality was 25% in the Conc_OLT group (n = 2) and lower compared to 71% observed in the Iso_Surg group (n = 5, p = 0.13). CONCLUSION: Concomitant cardiac surgery and OLT is a promising alternative compared to isolated cardiac surgery in high risk patients with ESLD. Given the high operative mortality of cardiac surgery in patients with ESLD, the complex peri-operative management of these patients should be performed in an interdisciplinary team with an expert team of liver specialists involved.

Runting and Stunting Syndrome in Broiler Chickens: Histopathology and Association With a Novel Picornavirus.

Runting stunting syndrome (RSS) in commercial chickens has been reported worldwide, and although several studies have attempted to clarify the cause and describe the lesions, there are gaps in knowledge of the epidemiology, pathogenesis, and etiology. The study objective was to use commercial chicks naturally affected by RSS to describe the histologic changes of RSS in all segments of the small intestine in chicks of different ages and to identify viral gene sequences in affected chicks and their association with histologic lesions. Chicks lacking clinical signs but from the same houses and from unaffected houses were used as controls. The average weight of affected chicks was significantly lower than expected for their flocks. Macroscopically, the small intestines had paler serosa, with watery, mucoid, or foamy contents and poorly digested food. Histologic lesions were characterized by necrotic crypts, crypt dilation, and flattening of the crypt epithelium. Histomorphometry of the intestines revealed villous atrophy especially in the jejunum and ileum. Histologic changes in other organs were not observed. Random next-generation sequencing of total RNA extracted from formalin-fixed paraffin-embedded tissues detected avian nephritis virus, avian rotavirus, and picornavirus in jejunal segments from 7-day-old chicks. No viruses were detected in the jejunum of 1-day-old chicks. Detection of picornaviral reads was significantly associated (P < .05) with histologic lesions of RSS. Sequence analysis of the picornavirus revealed genetic similarity with the genus Gallivirus. Using in situ hybridization for galliviral nucleic acid sequences, the signal was associated with crypt lesion severity, although signal was detected both in chicks with and without RSS.

Newcastle disease virus induces testicular damage and disrupts steroidogenesis in specific pathogen free roosters.

Newcastle disease (ND), which is caused by Newcastle disease virus (NDV), can cause heavy economic losses to the poultry industry worldwide. It is characterised by extensive pathologies of the digestive, respiratory, and nervous systems and can cause severe damage to the reproductive system of egg-laying hens. However, it is unknown whether NDV replicates in the male reproductive system of chickens and induces any pathologies. In this study, we selected a representative strain (i.e. ZJ1) of the most common genotype (i.e. VII) of NDV to investigate whether NDV can induce histological, hormonal, and inflammatory responses in the testes of specific pathogen free (SPF) roosters. NDV infection increased the expression of toll like receptor TLR3, TLR7, MDA5, IFN-α, IFN-ß, IFN-γ, IL-8, and CXCLi1 in the testes of NDV-infected roosters at 5 days post-infection (dpi). Severe histological changes, including decrease in the number of Sertoli cells and individualized, shrunken spermatogonia with pyknotic nuclei, were observed at 3 dpi. At 5 dpi, the spermatogenic columns were disorganized, and there were fewer cells, which were replaced by necrotic cells, lipid vacuoles, and proteinaceous homogenous material. A significant decrease in the plasma concentrations of testosterone and luteinizing hormone (LH) and the mRNA expression of their receptors in the testes, steroidogenic acute regulatory protein, cytochrome P450 side-chain cleavage enzyme, and 3ß-hydroxysteroid dehydrogenase in the NDV-infected group was observed relative to those in the control group (P < 0.05). Collectively, these results indicate that NDV infection induces a severe inflammatory response and histological changes, which decrease the steroidogenesis.