A Proinflammatory Gut Microbiota Increases Systemic Inflammation and Accelerates Atherosclerosis.

RATIONALE: Several studies have suggested a role for the gut microbiota in inflammation and atherogenesis. A causal relation relationship between gut microbiota, inflammation, and atherosclerosis has not been explored previously. OBJECTIVE: Here, we investigated whether a proinflammatory microbiota from Caspase1-/- ( Casp1-/-) mice accelerates atherogenesis in Ldlr-/- mice. METHOD AND RESULTS: We treated female Ldlr-/- mice with antibiotics and subsequently transplanted them with fecal microbiota from Casp1-/- mice based on a cohousing approach. Autologous transplantation of fecal microbiota of Ldlr-/- mice served as control. Mice were cohoused for 8 or 13 weeks and fed chow or high-fat cholesterol-rich diet. Fecal samples were collected, and factors related to inflammation, metabolism, intestinal health, and atherosclerotic phenotypes were measured. Unweighted Unifrac distances of 16S rDNA (ribosomal DNA) sequences confirmed the introduction of the Casp1-/- and Ldlr-/- microbiota into Ldlr-/- mice (referred to as Ldlr-/-( Casp1-/-) or Ldlr-/-( Ldlr-/-) mice). Analysis of atherosclerotic lesion size in the aortic root demonstrated a significant 29% increase in plaque size in 13-week high-fat cholesterol-fed Ldlr-/-( Casp1-/-) mice compared with Ldlr-/-( Ldlr-/-) mice. We found increased numbers of circulating monocytes and neutrophils and elevated proinflammatory cytokine levels in plasma in high-fat cholesterol-fed Ldlr-/-( Casp1-/-) compared with Ldlr-/-( Ldlr-/-) mice. Neutrophil accumulation in the aortic root of Ldlr-/-( Casp1-/-) mice was enhanced compared with Ldlr-/-( Ldlr-/-) mice. 16S-rDNA-encoding sequence analysis in feces identified a significant reduction in the short-chain fatty acid-producing taxonomies Akkermansia, Christensenellaceae, Clostridium, and Odoribacter in Ldlr-/-( Casp1-/-) mice. Consistent with these findings, cumulative concentrations of the anti-inflammatory short-chain fatty acids propionate, acetate and butyrate in the cecum were significantly reduced in 13-week high-fat cholesterol-fed Ldlr-/-( Casp1-/-) compared with Ldlr-/-( Ldlr-/-) mice. CONCLUSIONS: Introduction of the proinflammatory Casp1-/- microbiota into Ldlr-/- mice enhances systemic inflammation and accelerates atherogenesis.

Primary Aortoduodenal Fistula: A Case Report and Current Literature Review.

Primary aortoduodenal fistula is a rare, life-threatening pathology that is difficult to diagnose and manage. We present the case of a 64-year-old male with a primary aortoduodenal fistula. Our patient initially underwent an endovascular aneurysm repair at an outside institution before being transferred to our tertiary care center, where he ultimately had definitive management with an extra-anatomic bypass, aortic ligation, duodenal resection with primary anastomosis, and gastrojejunostomy tube placement. His surgical cultures grew Candida albicans, and he was discharged with a 6-week course of intravenous antibiotics with subsequent antibiotic suppression for 1 year. He died 14 months postoperatively from tongue squamous cell carcinoma. We also review the current literature regarding epidemiology, pathology, diagnostics, management, and case reports from 2015 to present. Overall, timely diagnosis and treatment is imperative for reducing mortality from primary aortoduodenal fistula, and although formal consensus is lacking regarding most clinical aspects, an increasing number of case reports has helped describe options for management.

Trying to Survive A Serious Heart Condition in Time of COVID-19.

The world has suffered over the past year under COVID-19. Unfortunately, people still are getting sick from other, also severe, diseases. Although the COVID-19 infection is present, patients need treatment for other life-threatening conditions. We present the case of a 36-year-old patient with severe infective endocarditis with a large abscess of the aortic root, who also is COVID-19 positive. Definitive diagnostics and treatment were avoided due to COVID-19 infection. In the end, emergent surgery was indicated due to acute cardiac decompensation and the development of heart failure symptoms, and the patient recovered uneventfully after surgery.

Impact of Gut Microbiota and Diet on the Development of Atherosclerosis in Apoe-/- Mice.

Objective- To investigate the effect of gut microbiota and diet on atherogenesis. Approach and Results- Here, we investigated the interaction between the gut microbiota and diet on atherosclerosis by feeding germ-free or conventionally raised Apoe-/- mice chow or Western diet alone or supplemented with choline (which is metabolized by the gut microbiota and host enzymes to trimethylamine N-oxide) for 12 weeks. We observed smaller aortic lesions and lower plasma cholesterol levels in conventionally raised mice compared with germ-free mice on a chow diet; these differences were not observed in mice on a Western diet. Choline supplementation increased plasma trimethylamine N-oxide levels in conventionally raised mice but not in germ-free mice. However, this treatment did not affect the size of aortic lesions or plasma cholesterol levels. Gut microbiota composition was analyzed by sequencing of 16S rRNA genes. As expected, the global community structure and relative abundance of many taxa differed between mice fed chow or a Western diet. Choline supplementation had minor effects on the community structure although the relative abundance of some taxa belonging to Clostridiales was altered. Conclusions- In conclusion, the impact of the gut microbiota on atherosclerosis is dietary dependent and is associated with plasma cholesterol levels. Furthermore, the microbiota was required for trimethylamine N-oxide production from dietary choline, but this process could not be linked to increased atherosclerosis in this model.

Late ascending aortic prosthesis infection by Porphyromonas pogonae: An unexpected infectious complication.

Late complications in ascending aortic surgeries are uncommon and may occur by infectious processes, usually caused by gram positive bacteria. We report a case of aortic prosthesis infection by Porphyromonas pogonae, an anaerobic gram-negative coccobacillus that can grow under microaerobic conditions, three years after ascending aortic reconstruction surgery.

Regulation of calcification in human aortic smooth muscle cells infected with high-glucose-treated Porphyromonas gingivalis.

Porphyromonas (P.) gingivalis infection leading to the periodontitis has been associated with the development of systemic diseases, including cardiovascular diseases and diabetes. However, the effect of a high concentration of glucose (HG) on the invasion efficiency of P. gingivalis and the consequent modulation of pathogenesis in vascular cells, especially in the vascular smooth muscle cells (VSMCs), remains unclear. Hence, the aim of this study was to investigate whether treating P. gingivalis with HG could change its invasion capability and result in VSMC calcification and the underlying mechanism. Human aortic SMCs (HASMCs) and P. gingivalis strain CCUG25226 were used in this study. We found that HGPg infection of HASMCs could initiate the HASMC calcification by stimulating the autocrine regulation of bone morphogenetic protein (BMP) 4 in HASMCs. The upregulation of BMP4 expression in HASMCs was mediated by toll-like receptor 4 and ERK1/2-p38 signaling after P. gingivalis infection. Moreover, the autocrine action of BMP4 in HGPg infection-initiated HASMC calcification upregulated BMP4-specific downstream smad1/5/8-runx2 signaling to increase the expressions of bone-related matrix proteins, that is, osteopontin, osteocalcin, and alkaline phosphatase. This study elucidates the detailed mechanism of HGPg infection-initiated calcification of HASMCs and indicates a possible therapeutic role of BMP4 in P. gingivalis infection-associated vascular calcification.

First Robinsoniella peoriensis aortic cross homograft mycotic pseudoaneurysm: A case report and review of the literature.

Mycotic aortic aneurysm is a rare and challenging complication of aortic homografts caused by an infection and is associated with high morbidity and mortality. We report the first case of an aortic cross homograft mycotic pseudoaneurysm caused by Robinsoniella peoriensis in a 70-year-old man. Our patient underwent surgery for a recurrence of aortic cross mycotic pseudoaneurysm at the level of the aortic homograft he had had 7 years before. A clot-removal of the pseudoaneurysm was surgically carried out and the homograft was completely removed. Anaerobic culture from tissue samples yielded pure growth of a spore-forming Gram-positive rod, identified later as Robinsoniella peoriensis by 16S rRNA gene sequencing. The patient was then discharged with oral clindamycin according to the in vitro susceptibility testing. Identification of R. peoriensis might be challenging in clinical laboratories with no access to molecular methods.

Endocarditis With Fistulization and Rupture of Aortic Root Abscess to the Left Atrium.

BACKGROUND: Infective endocarditis (IE) is a difficult emergency department (ED) diagnosis to make. Symptoms are nonspecific and diverse and the classic triad of fever, anemia, and murmur is rare. Severe IE causes considerable morbidity and mortality and should be diagnosed early. However, echocardiogram is essential but not readily available in the ED and can cause diagnostic delay. CASE REPORT: This case describes severe IE and its unique presentation, diagnostic challenges, and the use of bedside cardiac ultrasonography. A 28-year-old previously healthy male presented with intermittent fevers, arthralgias, and myalgias for 2 weeks. He had twice been evaluated and diagnosed with lumbar back pain. Physical examination revealed moderate respiratory distress, pale skin with a cyanotic right lower extremity, and unequal extremity pulses. He became hypotensive and rapidly deteriorated. Chest x-ray study showed bilateral pulmonary infiltrates with subsequent imaging demonstrating worsening septic emboli. Bedside ultrasound revealed mitral and aortic valve vegetations and a presumed diagnosis of IE with septic embolization was made. Formal echocardiography (ECHO) confirmed IE with an aortic root abscess with rupture and fistulization into the left atrium. WHY SHOULD AN EMERGENCY PHYSICIAN BE AWARE OF THIS?: Clinical criteria for IE include blood cultures and ECHO, however, these are often not available to an emergency physician, making IE a diagnostic challenge even in severe cases. The role of bedside ultrasound for IE continues to evolve and its utility in the diagnosis of severe IE is distinctly demonstrated in this case.

A cannonball through the chest: disseminated tuberculosis, threatening the aortic arch.

BACKGROUND: In 2012 the World Health Organization reported 8.7 million new cases of Tuberculosis worldwide, causing 1.4 million deaths (1). Despite modern drug therapy, this disease continues to present in novel ways and mimic other diseases causing misdiagnosis. AIM: We report this case to educate on the reason to suspect atypical Tuberculosis presentation, even if a common disease is diagnosed, when Tuberculosis remains in the differential. We also demonstrate that with globalization and patient moving between countries, that these presentations can occur in locations, where such atypical manifestations are very uncommon. CASE: We report on a 48 year old man with one month of malaise, fever, productive cough, night sweats, chills, pleuritic chest pain, weight loss and progressive non-painful swelling on his thorax. Initial diagnoses of interstitial pneumonia and a thoracic subcutaneous abscess were made. Needle drainage was attempted, with thick purulent material returned. When the sternum was not struck with the needle, a thoracic computed tomography scan was performed. A milliary pattern was noted in the lungs, with a large abscess present anteriorly, completely obliterating the manubrium, approaching the aorta with distant lesions. Subsequent analysis showed the material to be pan-sensitive M. Tuberculosis. CONCLUSION: The issue that this case raises is that when tuberculosi is in the differential, even common diseases may in fact be atypical manifestations of tuberculosis. In addition, when a shallow surgical procedure is going to be performed on the thoracic soft tissues, particularly when tuberculosis is suspected, imaging of the thorax should be obtained.

Aortic thrombus and multiple embolisms during a Mycoplasma pneumoniae infection.

We report the case of a patient who presented with a thrombus of the aortic arch complicated with splenic, renal and peroneal artery embolisms, associated with transient lupus anticoagulant, during a Mycoplasma pneumoniae infection. The outcome was good under antibiotic and anticoagulant treatment. We also review the medical literature on M. pneumoniae-related thromboses.

Aortic endograft infection with aortoduodenal fistula associated with adjacent vertebral body mycobacterial osteomyelitis (Pott's disease).

Aortoenteric fistulas (AEFs) are a rare complication of infrarenal abdominal aortic aneurysm repair. They occur in <1% of aortic grafting procedures, result from graft defects, foreign bodies, and trauma, and are associated with a high mortality rate. We report a complex AEF associated with vertebral body osteomyelitis, likely secondary to tuberculous infection. A 78-year-old man presented with a 2-week history of abdominal pain, fever, and anemia. Past surgical history is significant for open repair of infrarenal abdominal aortic aneurysm followed later by an endovascular repair of a proximal para-anastomotic aneurysm. Computed tomography angiography revealed air in the aneurysm sac, without evidence of endoleak. The posterior aspect of the aneurysm was noted to be in continuity with a destructive osteomyelitis of the second lumbar vertebral body and an adjacent psoas abscess. Percutaneous drainage revealed purulent fluid containing mixed enteric flora. With fluoroscopic guidance, injection of contrast in the aortic sac drainage catheter demonstrated complex fistulous communications from the aortic sac to the overlying small intestine. After a course of drainage, antibiotic therapy, and parenteral nutrition, the patient underwent a transperitoneal repair of the AEF with duodeno-duodenectomy and wide debridement of the aortic sac and Dacron graft. Pathology revealed giant cell granulomas, highly suggestive of tuberculosis.

Cryopreserved arterial homografts vs silver-coated Dacron grafts for abdominal aortic infections with intraoperative evidence of microorganisms.

OBJECTIVE: The gold standard for the treatment of abdominal aortic infections remains controversial. Cryopreserved arterial homografts and silver-coated Dacron grafts have both been advocated as reasonable grafts. Direct clinical or experimental comparisons between these two treatment options have not been published before. This study compared cryopreserved arterial homografts and silver-coated Dacron grafts for the treatment of abdominal aortic infections in a contaminated intraoperative field. METHODS: From January 2004 to December 2009, 56 patients underwent in situ arterial reconstruction for an abdominal aortic infection. Patients with negative intraoperative microbiologic specimens were excluded. We compared 22 of 36 patients (61%) receiving cryopreserved arterial homografts (group A) vs 11 of 20 (55%) receiving a silver-coated Dacron graft (group B). Primary outcomes were survival and limb salvage; secondary outcomes were graft patency and reinfection. Direct costs of therapy were also calculated. RESULTS: Thirty-day mortality was 14% in group A and 18% in group B (P >.99), and 2-year survival rates were 82% and 73%, respectively (P = .79). After 2 years, limb salvage was 96% and 100%, respectively (P = .50), whereas graft patency was 100% for both groups. Major complications were an aneurysmal degeneration in group A and graft reinfection in group B (n = 2). Median direct costs of therapy (in US $) were $41,697 (range, $28,347-$53,362) in group A and $15,531 (range, $11,310-$22,209) in group B (P = .02). CONCLUSIONS: Our results show comparable effectiveness between cryopreserved arterial homograft and silver-coated Dacron graft in the contaminated operative field with respect to early mortality and midterm survival. Graft-inherent complications, aneurysmal degeneration for homografts, and reinfection for silver graft, were also observed. The in situ arterial reconstruction with homografts is nearly three times more expensive than with silver graft.

Hybrid aortic arch repair for a ruptured and infected penetrating atherosclerotic ulcer of the aortic arch.

Aortic arch rupture is a life-threatening emergency. Conventional open surgical repair carries a high mortality and morbidity. We report a case of an elderly patient who suffered from a ruptured and infected penetrating ulcer of the aortic arch. A hybrid operation was performed, consisting of a right-to-left carotid bypass and transposition of the left subclavian artery into the left common carotid artery followed by endovascular repair of the aortic arch. Antibiotic therapy, based on the results of culture and sensitivity tests for Staphylococcus aureus, was administered for 6 months. The patient recovered uneventfully and remains asymptomatic 16 months after the procedure. However, long-term follow-up is mandatory to determine the efficacy and the durability of this technique.

Infections of the aorta and iliac arteries. Report of 20 years experience in a single centre.

AIM: Retrospective review of aorto-iliac infections in a single vascular surgery center. METHODS: From a retrospective review of their experience in the last 20 years, the Authors analyze a series of 12 cases of aorto-iliac infection. Prognostic factors, surgical options and results are discussed and compared with the literature. RESULTS: Infections of the aorta eventually associated with aneurysmal degeneration are uncommon (less than 3% of all aortic aneurysms) but still a life-threatening condition with high hospital mortality (25%). No statistical evaluation can be drawn from small series; however, early results are apparently influenced by emergency surgery and comorbidities affecting the immune response; in-situ reconstruction is associated with better long-term results (patency 100%, recurrent infection 0%). CONCLUSIONS: In our experience, in situ aortic grafting reconstruction associated with proper antibiotic therapy obtained satisfactory results in terms of mortality and long-term survival Endovascular treatment can be adopted in critical patients with prohibitive surgical risk.

Management of a thoracic endograft infection through an ascending to descending extra-anatomic aortic bypass and endograft explantation.

A 52-year-old man presented 33 months after thoracic aortic endovascular repair with hemoptysis and was found to have an aortobronchial fistula secondary to a mycotic aneurysm. The endograft infection was managed in a two-stage fashion. During the initial stage, the patient underwent an ascending-to-descending thoracic aortic bypass. Neither cardiopulmonary bypass, hypothermic circulatory arrest, nor aortic cross-clamping were used. During the same hospitalization, the patient underwent successful endograft explantation through a left thoracotomy. Imaging at 6 months demonstrated no anastomotic concerns and resolution of residual pulmonary inflammation. Thoracic aortic endograft infections necessitating endograft removal can potentially be successfully and safely managed without the need for cardiopulmonary bypass, hypothermic circulatory arrest, or interruption of aortic blood flow.

Eight-year experience with cryopreserved arterial homografts for the in situ reconstruction of abdominal aortic infections.

OBJECTIVE: This study investigated short-term and long-term outcomes in patients with abdominal aortic infection (mycotic aneurysm, prosthetic graft infection, aortoenteric fistula) managed by total excision of the aneurysm or the infected vascular graft and in situ aortic reconstruction with a cryopreserved arterial homograft (CAH). METHODS: From January 2000 to December 2008, 110 consecutive patients underwent CAH implantation for treatment of vascular infections. In 57 (52%), in situ revascularization of the abdominal aorta with Y-prosthesis constructed from CAHs was performed. Early outcome included 30-day mortality and the levels of daily blood markers (leucocytes, C-reactive protein, and platelets) during the postsurgical 10-day period. We reported long-term survival and freedom from reoperation rates, including all indications for reoperation. RESULTS: Indications for operation were infected vascular graft in 31 patients (55%), aortodigestive fistulae in 11 (19%), nonruptured mycotic aneurysms in 4 (7%), and ruptured mycotic aneurysms of abdominal aorta in 11 (19%). In 39 of 57 patients (68%), the intraoperative specimens were positive for at least one microorganism, and Staphylococcus aureus was present in 14 (25%). In 32 patients (82%) with intraoperative specimens positive for microorganisms, there was no evidence of the intraoperatively detected microorganisms in the postoperative specimens (wound, blood culture, and drainage fluid). The peak value of leucocytes (13.7 +/- 4.4 x 10(3)/L) and C-reactive protein (200 +/- 75 mg/L) occurred on postoperative day 3. Platelets reached the lowest value on postoperative day 2 (178 +/- 67 x 10(9)/L). Median peak body temperature was 37.7 degrees +/- 0.6 degrees C. Thirty-day mortality was 9% (5 of 57 patients). Median follow-up was 36 months (range, 4-118 months); 3-year survival was 81%, and freedom from reoperation was 89%. Five patients (9%) required reoperation, in one patient each for postoperative bleeding, acute cholecystitis, homograft occlusion, homograft-duodenum fistula, and aneurysmal degeneration. No recurrence of infection was reported. CONCLUSION: These results demonstrate an encouraging outcome after cryopreserved allograft implantation for the treatment of vascular infections in the abdominal aorta. The data represent a basis for future comparisons with other treatment modalities for vascular infections, including silver-coated prostheses and autogenous femoral veins.

Epidemiology and diagnosis of endograft infection.

Endograft infection is reported to occur in between 0.2 and 0.7 of patients and in general presents either within four months of endograft implantation of after more than 12 months. Review of all cases reported to date reveals three modes of presentation: approximately one third of patients present with evidence of an aorto-enteric fistula (although less than half of these present with gastrointestinal haemorrhage), one third present with non specific signs of low grade sepsis (malaise, weight loss) and the remainder with evidence of severe systemic sepsis. Infection is most commonly attributed to Staphylococcus aureus. Diagnosis relies on a high index of suspicion, imaging of the aorta and periaortic tissues (computed tomography or magnetic resonance imaging) and bacteriological culture. This paper presents a detailed analysis of the features of all cases reported to date and examines the aetiology, pathogenesis and imaging of endograft infection and aorto-enteric fistula.