A large panel of chicken cells are invaded in vivo by Salmonella Typhimurium even when depleted of all known invasion factors.

Poultry are the main source of human infection by Salmonella. As infected poultry are asymptomatic, identifying infected poultry farms is difficult, thus controlling animal infections is of primary importance. As cell tropism is known to govern disease, our aim was therefore to identify infected host-cell types in the organs of chicks known to be involved in Salmonella infection and investigate the role of the three known invasion factors in this process (T3SS-1, Rck and PagN). Chicks were inoculated with wild-type or isogenic fluorescent Salmonella Typhimurium mutants via the intracoelomic route. Our results show that liver, spleen, gall bladder and aortic vessels could be foci of infection, and that phagocytic and non-phagocytic cells, including immune, epithelial and endothelial cells, are invaded in vivo in each organ. Moreover, a mutant defective for the T3SS-1, Rck and PagN remained able to colonize organs like the wild-type strain and invaded non-phagocytic cells in each organ studied. As the infection of the gall bladder had not previously been described in chicks, invasion of gall bladder cells was confirmed by immunohistochemistry and infection was shown to last several weeks after inoculation. Altogether, for the first time these findings provide insights into cell tropism of Salmonella in relevant organs involved in Salmonella infection in chicks and also demonstrate that the known invasion factors are not required for entry into these cell types.

Oral Treponema denticola Infection Induces Aß1-40 and Aß1-42 Accumulation in the Hippocampus of C57BL/6 Mice.

Accumulation of amyloid-ß (Aß) in the brain is a central component of pathology in Alzheimer's disease. A growing volume of evidence demonstrates close associations between periodontal pathogens including Porphyromonas gingivalis (P. gingivalis) and Treponema denticola (T. denticola) and AD. However, the effect and mechanisms of T. denticola on accumulation of Aß remain to be unclear. In this study, we demonstrated that T. denticola was able to enter the brain and act directly on nerve cells resulting in intra- and extracellular Aß1-40 and Aß1-42 accumulation in the hippocampus of C57BL/6 mice by selectively activating both ß-secretase and γ-secretase. Furthermore, both KMI1303, an inhibitor of ß-secretase, as well as DAPT, an inhibitor of γ- secretase, were found to be able to inhibit the effect of T. denticola on Aß accumulation in N2a neuronal cells. Overall, it is concluded that T. denticola increases the expression of Aß1-42 and Aß1-40 by its regulation on beta-site amyloid precursor protein cleaving enzyme-1 and presenilin 1.

[18F-fluorodeoxyglucose PET/CT in the diagnosis of vascular graft infection]. / Vozmozhnosti PET/KT S 18F-ftordezoksiglyukozoi v diagnostike infektsii sosudistykh protezov.

OBJECTIVE: To investigate diagnostic role of 18F-fluorodeoxyglucose PET/CT in patients with suspected vascular graft (VG) infection. MATERIAL AND METHODS: A prospective analysis included data of 30 PET/CT examinations for suspected infection of aortic VG (n=27) and bypass grafts (n=3) after surgical treatment (median 48 months). In 77% (23/30) of cases, the diagnosis was initially «possible¼ (n=11) or «rejected¼ (n=12) in accordance with common diagnostic criteria. All PET/CT results were verified by clinical, laboratory and intraoperative («=20) data. VG infection was confirmed in 18 patients and ruled out in 12 cases. RESULTS: PET/CT confirmed VG infection in 94% (17/18) and excluded in 50% (6/12) of cases. False PET/CT results were obtained in 23% (7/30) cases: false positive in 6 cases and false negative in 1 case. Thus, sensitivity, specificity and diagnostic accuracy of PET/CT were 94%, 50% and 77%, respectively; positive and negative predictive value - 74% and 86%. PET/CT results allowed correct reclassifying 33% (10/30) of cases. VG infection was confirmed in 73% (8/11) of patients with initially «possible¼ diagnosis and excluded in 17% (2/12) of patients with initially «rejected¼ infection. Moreover, whole body PET/CT revealed unknown inflammation foci outside VG in 73% (22/30) of cases. These data were applied to correct treatment approach in 80% (24/30) of cases. CONCLUSION: Our results showed high efficacy of 18F-fluorodeoxyglucose PET/CT in the diagnosis of VG infection. Despite low specificity, this technique has high sensitivity and accuracy that allowed reclassifying 33% of cases.

The effect of baicalin on microRNA expression profiles in porcine aortic vascular endothelial cells infected by Haemophilus parasuis.

Glässer's disease, caused by Haemophilus parasuis (H. parasuis), is associated with vascular damage and vascular inflammation in pigs. Therefore, early assessment and treatment are essential to control the inflammatory disorder. MicroRNAs have been shown to be involved in the vascular pathology. Baicalin has important pharmacological functions, including anti-inflammatory, antimicrobial and antioxidant effects. In this study, we investigated the changes of microRNAs in porcine aortic vascular endothelial cells (PAVECs) induced by H. parasuis and the effect of baicalin in this model by utilizing high-throughput sequencing. The results showed that 155 novel microRNAs and 76 differentially expressed microRNAs were identified in all samples. Subsequently, Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis of the target genes of the differentially expressed microRNAs demonstrated that regulation of actin cytoskeleton, focal adhesion, ECM-receptor interaction, bacterial invasion of epithelial cells, and adherens junction were the most interesting pathways after PAVECs were infected with H. parasuis. In addition, when the PAVECs were pretreated with baicalin, mismatch repair, peroxisome, oxidative phosphorylation, DNA replication, and ABC transporters were the most predominant signaling pathways. STRING analysis showed that most of the target genes of the differentially expressed microRNAs were associated with each other. The expression levels of the differentially expressed microRNAs were negatively co-regulated with their target genes' mRNA following pretreatment with baicalin in the H. parasuis-induced PAVECs using co-expression networks analysis. This is the first report that microRNAs might have key roles in inflammatory damage of vascular tissue during H. parasuis infection. Baicalin regulated the microRNAs changes in the PAVECs following H. parasuis infection, which may represent useful novel targets to prevent or treat H. parasuis infection.

Syphilitic aortitis: still a current common cause of aneurysm of the tubular portion of ascending aorta.

Aortic syphilis today is infrequently diagnosed clinically. Described herein are findings in 5 women who had resection of a fusiform aneurysm of the tubular portion of ascending aorta, and examination of the wall of the aneurysm disclosed classic features of aortic syphilis. The 5 patients were among 36 who had ascending aortic operations at Baylor University Medical Center in Dallas in 2018 and early 2019. Syphilitic aneurysm in each spared the sinus portion and involved diffusely the tubular portion of ascending aorta, beginning at the sinotubular junction. The aneurysmal wall was thicker than normal because of thickening of both intima and adventitia. The latter contained foci of lymphocytes and plasmacytes and thickened and narrowed vasa vasora. The media was disrupted by fibrous scars, which weakened the integrity of the aorta. Aortitis of the tubular portion of ascending aorta in syphilis is a diffuse process, but often is mistakenly called "atherosclerosis" which, when present in this portion of aorta, can be extensive but is focal. Aortic syphilis is important to diagnose so that patients can receive antibiotic therapy to delay, prevent, or treat neurosyphilis, a common accompaniment of aortic syphilis.

Mycobacterium bovis Bacille-Calmette-Guérin Infection Aggravates Atherosclerosis.

Tuberculosis has been associated with increased risk of atherosclerotic cardiovascular disease. To examine whether mycobacterial infection exacerbates atherosclerosis development in experimental conditions, we infected low-density lipoprotein receptor knockout (Ldlr-/-) mice with Mycobacterium bovis Bacille-Calmette-Guérin (BCG), an attenuated strain of the Mycobacterium tuberculosis complex. Twelve-week old male Ldlr-/- mice were infected with BCG (0.3-3.0x106 colony-forming units) via the intranasal route. Mice were subsequently fed a western-type diet containing 21% fat and 0.2% cholesterol for up to 16 weeks. Age-matched uninfected Ldlr-/- mice fed with an identical diet served as controls. Atherosclerotic lesions in aorta were examined using Oil Red O staining. Changes induced by BCG infection on the immunophenotyping profile of circulating T lymphocytes and monocytes were assessed using flow cytometry. BCG infection increased atherosclerotic lesions in en face aorta after 8 weeks (plaque ratio; 0.021±0.01 vs. 0.013±0.01; p = 0.011) and 16 weeks (plaque ratio, 0.15±0.13 vs. 0.06±0.02; p = 0.003). No significant differences in plasma cholesterol or triglyceride levels were observed between infected and uninfected mice. Compared to uninfected mice, BCG infection increased systemic CD4/CD8 T cell ratio and the proportion of Ly6Clow non-classical monocytes at weeks 8 and 16. Aortic plaque ratios correlated with CD4/CD8 T cell ratios (Spearman's rho = 0.498; p = 0.001) and the proportion of Ly6Clow non-classical monocytes (Spearman's rho = 0.629; p < 0.001) at week 16. In conclusion, BCG infection expanded the proportion of CD4+ T cell and Ly6Clow monocytes, and aggravated atherosclerosis formation in the aortas of hyperlipidemic Ldlr-/- mice. Our results indicate that mycobacterial infection is capable of enhancing atherosclerosis development.

Successful long-term antibiotic suppressive therapy in a case of prosthetic valve endocarditis and a case of extensive aortic and subclavian graft infection.

INTRODUCTION: The indication for surgical valve replacement in cases of infective endocarditis is well defined in current guidelines. However, some patients are not fit or willing to undergo major surgical procedures. Interestingly, to the best of our knowledge, there is scarce information in the literature on how to deal with such cases and what might be the outcome. CASE REPORT: We present two complicated cases of prosthetic infective endocarditis with definite indication for replacement of involved foreign material, who were treated successfully with long-term suppressive antibiotic therapy. CONCLUSION: These two cases demonstrate that individualized long-term antibiotic suppressive therapy might be effective in selected patients with complicated PVE unfit or unwilling to undergo high-risk cardiothoracic surgical interventions.

Oral challenge with Streptococcus sanguinis induces aortic inflammation and accelerates atherosclerosis in spontaneously hyperlipidemic mice.

Atherosclerosis is exacerbated by periodontal pathogens, which induce vascular inflammation after entering the bloodstream. Among oral indigenous bacteria, Streptococcus sanguinis and S. anginosus are related to systemic disorders, such as infective endocarditis and abscess, and are sometimes detected in human atherosclerotic plaques or blood. Thus, these oral streptococci may contribute to the progression of atherosclerosis. To test this hypothesis, apolipoprotein E-deficient spontaneously hyperlipidemic mice were intraorally challenged with S. sanguinis or S. anginosus. Atherosclerotic plaque formation increased significantly in the S. sanguinis-challenged group compared with the carboxymethylcellulose-treated control group. Expression levels of mRNAs of proinflammatory cytokines in the aorta and levels of atherosclerosis-related mediators in blood increased upon S. sanguinis challenge. Adaptor molecule TNF receptor-associated factor 6 was also enhanced in the aorta when mice were challenged with S. sanguinis. Furthermore, challenge with S. anginosus induced systemic inflammation, but inflammation-related mRNA expression levels in the aorta only increased slightly and were accompanied by minimal expansion of the lesion area. By contrast, with the exception of IL-1α, the expression levels of inflammation-related genes did not change in gingival tissues of both bacteria- and sham-challenged groups. These results reveal that S. sanguinis causes aortic inflammation that leads to accelerated progression of atherosclerosis.

Aortic reconstruction in infected aortic pathology by femoral vein "neo-aorta".

The use of autologous femoral veins for in situ reconstruction of the aortoiliac segment is an effective technique to treat native aorta or prosthetic graft infections. The indications, technical details, and outcomes of this procedure are detailed. Graft infection involving the aortic segment, while rare, remains one of the most challenging vascular surgery conditions to treat. The original technique of "neo-aortoiliac surgery" with in situ autologous vein grafts has evolved over the past 25 years and remains a worthwhile alternative for the treatment of aortic graft infections, with lower mortality rates compared with other extra-anatomic or in situ surgical options. Acceptance of this surgical option is due to low graft re-infection rates, rare graft disruption, and low long-term aneurysmal degeneration. Excision of the femoral veins is associated with acceptable rates of lower limb edema. The use of an autologous femoral vein graft can be considered the standard of care in selected patients for the management of aortic graft infections. Optimal management of patients with aortic graft infections requires consideration of all potential therapeutic options because no single modality can be used, and individualizing treatment according to the clinical condition will yield the best patient outcomes.

Current status of treatment for aortic graft infection: When should cryopreserved allografts be used?

Aortic graft infection remains one of the most complex clinical challenges faced by vascular specialists, and is often associated with significant patient morbidity and mortality regardless of the approach used for management. The cryopreserved aortic allograft is now a commonly used in situ aortic replacement in the management of graft infection, and is preferred over rifampin-soaked prosthetic grafts. In the review, we summarize the indications for cryopreserved aortic allograft usage, as well as operative technique, clinical results, and alternative treatments. We propose the use of a novel term tertiary aortic fistula, to distinguish aortic fistulae in the setting of aortic endograft infection, a clinical entity whose natural history and best management are currently being characterized.

The First Report of Purulent Pericarditis Associated with Aortic Stent-graft Infection Caused by Methicillin-susceptible Staphylococcus aureus.

We herein report the first case of purulent pericarditis associated with aortic stent-graft infection in an 80-year-old Japanese man that was caused by methicillin-susceptible Staphylococcus aureus, which appropriate antibiotics failed to treat. The detailed clinical course and autopsy images revealed that purulent pericarditis associated with aortic stent-graft infection caused cardiac tamponade and eventually led to mortality. We therefore suggest that surgical procedures, including drainage, should be introduced for such cases.

Bartonella Quintana prosthetic aortitis successfully treated with doxycycline.

Bartonella quintana is a rare cause of culture-negative endovascular infection, characterised by intracellular persistence. We describe a case of ascending aortic prosthetic graft infection due to B. quintana, in a patient with past unrecognised necrotising aortitis, which was successfully treated with doxycycline monotherapy.

Systematic review of native and graft-related aortic infection outcome managed with orthotopic xenopericardial grafts.

OBJECTIVE: Limited data are available on the use of xenopericardium in the treatment of native and graft-related aortic infections. The aim of this review was to assess outcomes of neoaortic reconstruction using xenopericardium in this challenging group of patients. METHODS: Studies involving xenopericardial graft reconstruction to treat native and aortic graft infections were systematically searched and reviewed (Embase, Medline, and Cochrane databases) for the period of January 2007 to December 2017. RESULTS: A total of 4 studies describing 71 patients treated for aortic graft (n = 54) and native aortic (n = 17) infections were included; 25 patients (35%) were operated on in an acute setting. The technical success rate was 100%. The mean 30-day mortality was 25% (range, 7.7%-31%). Only one death (1.4%) was linked to the operator-made pericardial tube graft (acute postoperative bleeding from proximal anastomosis). Septic multiorgan failure was the most common cause of perioperative death (72% [13/18]). Among the 53 patients who survived, only 3 presented with recurrent infection (5.7%), so 70.4% of patients were alive after intervention without evidence of infection (50/71). During follow-up, 2 false aneurysms (3.7% [2/53]), 1 early rupture (1.4% [1/71]), and 2 cases (3.7% [2/53]) of late rupture were reported. Other causes of late deaths unrelated to the aortic xenopericardial repair were not reported in the different series. The early reintervention rate was 1.4% (1/71), treated by open repair for rupture. The late reintervention rate was 7.5% (4/53) with thoracic endovascular aortic repair in three patients (one false aneurysm and two ruptures) and open repair in one patient (one false aneurysm). There were no cases of early or late graft thrombosis. One-year mortality rate was 38% but only 4.2% were related to the aortic repair using orthotopic xenopericardium (one early and two late ruptures). CONCLUSIONS: These data confirm the high morbidity of native and graft-related aortic infections and provide insight into the results of orthotopic xenografts as a treatment alternative. Larger series and longer follow-up will be required to compare the role of operator-made pericardial tube graft with other treatment options in infected fields.

Gut Colonization with Methanogenic Archaea Lowers Plasma Trimethylamine N-oxide Concentrations in Apolipoprotein e-/- Mice.

A mechanistic link between trimethylamine N-oxide (TMAO) and atherogenesis has been reported. TMAO is generated enzymatically in the liver by the oxidation of trimethylamine (TMA), which is produced from dietary choline, carnitine and betaine by gut bacteria. It is known that certain members of methanogenic archaea (MA) could use methylated amines such as trimethylamine as growth substrates in culture. Therefore, we investigated the efficacy of gut colonization with MA on lowering plasma TMAO concentrations. Initially, we screened for the colonization potential and TMAO lowering efficacy of five MA species in C57BL/6 mice fed with high choline/TMA supplemented diet, and found out that all five species could colonize and lover plasma TMAO levels, although with different efficacies. The top performing MA, Methanobrevibacter smithii, Methanosarcina mazei, and Methanomicrococcus blatticola, were transplanted into Apoe-/- mice fed with high choline/TMA supplemented diet. Similar to C57BL/6 mice, following initial provision of the MA, there was progressive attrition of MA within fecal microbial communities post-transplantation during the initial 3 weeks of the study. In general, plasma TMAO concentrations decreased significantly in proportion to the level of MA colonization. In a subsequent experiment, use of antibiotics and repeated transplantation of Apoe-/- mice with M. smithii, led to high engraftment levels during the 9 weeks of the study, resulting in a sustained and significantly lower average plasma TMAO concentrations (18.2 ± 19.6 µM) compared to that in mock-transplanted control mice (120.8 ± 13.0 µM, p < 0.001). Compared to control Apoe-/- mice, M. smithii-colonized mice also had a 44% decrease in aortic plaque area (8,570 µm [95% CI 19587-151821] vs. 15,369 µm [95% CI [70058-237321], p = 0.34), and 52% reduction in the fat content in the atherosclerotic plaques (14,283 µm [95% CI 4,957-23,608] vs. 29,870 µm [95% CI 18,074-41,666], p = 0.10), although these differences did not reach significance. Gut colonization with M. smithii leads to a significant reduction in plasma TMAO levels, with a tendency for attenuation of atherosclerosis burden in Apoe-/- mice. The anti-atherogenic potential of MA should be further tested in adequately powered experiments.

Infection with Staphylococcus aureus elicits COX-2/PGE2/IL-6/MMP-9-dependent aorta inflammation via the inhibition of intracellular ROS production.

Staphylococcus aureus (S. aureus) can lead to many life-threatening diseases. It has the ability to invade normal endovascular tissue. The molecular mechanisms and pathological changes of endothelial cells after S. aureus infection are of interest, but the basic understanding of how S. aureus destroys this barrier is not clear. Here, we showed that S. aureus enhanced COX-2 expression and prostaglandin E2 (PGE2) secretion in human aortic endothelial cells (HAECs). In addition, S. aureus induced PGE2/interleukin-6 (IL-6)/matrix metallopeptidase-9 (MMP-9)-dependent cell migration. S. aureus-induced COX-2, IL-6, and MMP-9 levels were inhibited by transfection with siRNA of Toll-like receptor 2 (TLR2), p38, p42, p44, p50, or p65. S. aureus also induced p38 MAPK, ATF2, ERK1/2, and NF-κB p65 activation. Interestingly, we proved that S. aureus decreased intracellular generation of reactive oxygen species (ROS), which suggests that the inhibition of ROS production promoted inflammatory responses. Finally, we showed that S. aureus enhanced a variety of biomarkers of inflammation in cardiovascular diseases. However, the free radical scavenger (MCI-186) or antioxidant (N-acetyl-L-cysteine, NAC) markedly enhanced S. aureus-induced COX-2 mRNA levels in the aorta tissues. Taken together, these findings established that S. aureus promoted aorta inflammation via activation of p38 MAPK, ERK1/2, and NF-κB and inhibition of ROS generation.

Current Evidence on Management of Aortic Stent-graft Infection: A Systematic Review and Meta-Analysis.

BACKGROUND: Aortic stent-graft infection (SGI) is rare but remains one of the most challenging and threatening complications. This systematic review aimed to identify the clinical features, treatment, and outcomes of endograft infection after abdominal endovascular aortic repair (EVAR) and thoracic endovascular aortic repair (TEVAR). METHODS: A systematic literature review of all published literature from January 1991 to September 2016 on SGI was performed under the instruction of Preferred Reporting Items for Systematic Reviews and Meta-Analyses. Aorta, aneurysm, endovascular, stent-graft, endograft and infection were the keywords used in our comprehensive search in PubMed and MEDLINE databases. Data analysis was performed using SPSS, V 22.0. RESULTS: A total of 185 potential relevant articles were identified, but only 11 studies with 402 patients met the inclusion criteria. Majority of the patients were male (308/402, 77%), with a mean age ranging from 65 to 73 years. Most of the endografts were implanted for EVAR (351/402, 87%), while the other 51 (13%) endografts were infected following TEVAR. Among the 402 patients, 39 (9.7%) patients presented with aortic rupture. Ninety-two of 380 (24.2%) patients with available data had aortoenteric fistula (AEF). Sixty-nine patients (17%) died in hospital or within 30 days after operation. One hundred fourteen patients (28%) died during follow-up. The most commonly used stent grafts were Zenith (Cook Inc, Bloomington, IN) (22%) and Excluder (W.L. Gore, Flagstaff, AZ) (20%). Of the 402 patients in this series, 108 patients (27%) had negative culture, and multiple microorganisms were identified in 103 patients (26%). The most frequently isolated microorganisms were Staphylcoccus species (30.1%), Streptococcus (14.8%), and fungus (9.2%). Forty-two patients (42/401, 10%) received conservative treatment, whereas 359 (90%) patients underwent surgical treatment, including stent graft removal with in situ reconstruction or extra-anatomical bypass, and secondary endovascular procedure. Patients in the surgical group had a higher survival rate compared with conservative group (58% vs. 33%, P = 0.002). The survival rate was higher in the patients with infected EVAR than TEVAR (58% vs. 27%, P = 0.000). Patient with AEF had a worse prognosis (survival rate 72% vs. 33%, P = 0.002). CONCLUSIONS: Current evidence suggests that surgical treatment is a better option compared with conservative management in selected patients with aortic endograft infection. The outcome was worse in patients with infected TEVAR and AEF.

Surgical management of ascending aortic pseudoaneurysm in a 2-year-old boy: a case report.

BACKGROUND: Aortic pseudoaneurysms are rare but life-threatening complications usually seen after cardiac surgery. The causes could be multifactorial such as infection or trauma. CASE PRESENTATION: We report the surgical management of a postoperative pseudoaneurysm of the ascending aorta caused by methicillin-resistant Staphylococcus aureus in a 2-year-old Middle Eastern boy who had undergone ventricular septal defect closure, subaortic membrane resection, and pulmonary artery de-banding. He was immediately operated on for resection of the aneurysm. A computed tomography scan at 2 months following surgery showed no aneurysm. Antibiotics were continued for 6 weeks and our patient was discharged with negative blood cultures. CONCLUSION: Early diagnosis and appropriate treatment of such rare complication can be lifesaving.