The exoprotein Gbp of Fusobacterium nucleatum promotes THP-1 cell lipid deposition by binding to CypA and activating PI3K-AKT/MAPK/NF-κB pathways.

INTRODUCTION: Growing evidence has shown the correlation between periodontitis and atherosclerosis, while our knowledge on the pathogenesis of periodontitis-promoting atherosclerosis is far from sufficient. OBJECTIVES: Illuminate the pathogenic effects of Fusobacterium nucleatum (F. nucleatum) on intracellular lipid deposition in THP-1-derived macrophages and elucidate the underlying pathogenic mechanism of how F. nucleatum promoting atherosclerosis. METHODS AND RESULTS: F. nucleatum was frequently detected in different kinds of atherosclerotic plaques and its abundance was positively correlated with the proportion of macrophages. In vitro assays showed F. nucleatum could adhere to and invade THP-1 cells, and survive continuously in macrophages for 24 h. F. nucleatum stimulation alone could significantly promote cellular inflammation, lipid uptake and inhibit lipid outflow. The dynamic gene expression of THP-1 cells demonstrated that F. nucleatum could time-serially induce the over-expression of multiple inflammatory related genes and activate NF-κB, MAPK and PI3K-AKT signaling pathways. The exoprotein of F. nucleatum, D-galactose-binding protein (Gbp), acted as one of the main pathogenic proteins to interact with the Cyclophilin A (CypA) of THP-1 cells and induced the activation of the NF- κB, MAPK and PI3K-AKT signaling pathways. Furthermore, use of six candidate drugs targeting to the key proteins in NF- κB, MAPK and PI3K-AKT pathways could dramatically decrease F. nucleatum induced inflammation and lipid deposition in THP-1 cells. CONCLUSIONS: This study suggests that the periodontal pathogen F. nucleatum can activate macrophage PI3K-AKT/MAPK/NF-κB signal pathways, promotes inflammation, enhances cholesterol uptake, reduces lipid excretion, and promotes lipid deposition, which may be one of its main strategies promoting the development of atherosclerosis.

Endovascular Treatment for Isolated Infected Iliac Artery Aneurysms.

PURPOSE: Isolated infected iliac artery aneurysms (IIIAAs) are extremely rare, life-threatening, and intractable. This study aimed to evaluate the outcomes of endovascular treatment in patients with IIIAAs. METHODS: A retrospective study was conducted for all patients who underwent endovascular treatment for IIIAAs between June 2012 and June 2022 in 3 hospitals. The clinical data and follow-up outcomes were reviewed and assessed. RESULTS: Fifteen patients were included in this study. The median age was 69 years, 12 patients (80%) were men, and 8 (53%) had hypertension. Most of the patients presented with abdominal or lumbar pain (87%) and fever (60%). The offending pathogen was identified in 11 patients (73%). Fifteen patients had a total of 16 IIIAAs, with 12 (75%) involving the common iliac artery. The immediate technical success rate was 100%, and the 30-day mortality was 7%. Infection-related complications occurred in 2 patients (13%) during hospitalization who were treated by open surgery at a later stage. The median follow-up was 23 months (range: 6-80 months, mean: 32 ± 25 months). Aneurysm recurrence was identified in one patient (7%) 5 months after endovascular repair. It was managed by endovascular stent-graft repair with percutaneous catheter drainage. No patients died during the follow-up period. CONCLUSION: Endovascular treatment is feasible, safe, and effective for patients with IIIAAs, achieving acceptable clinical outcomes. Infection surveillance with essential reintervention should be considered for potential infection-related complications. CLINICAL IMPACT: This study first reported that 15 patients underwent endovascular treatment for primary isolated infected iliac artery aneurysms (IIIAAs). It showed a good early and midterm outcomes. This is the first and largest multi-center study and the first literature review of IIIAAs. It provides an evidence that endovascular treatment is feasible, safe, and effective to treat IIIAAs. It suggests endovascular treatment is a promising alternative or a bridge to conventional open surgery for IIIAAs. This may promote endovascular therapy in the management of IIIAAs. It would help clinicians to make an appropriate treatment choice for IIIAAs.

Endovascular Stent Graft Repair for Mycotic Aorto-Iliac Aneurysm Due to Brucella.

PURPOSE: Brucella aneurysms are very rare but life-threatening, and a standard treatment approach has yet to be established. The current study aimed to assess the safety and efficacy of endovascular treatment for Brucella aneurysms. MATERIALS AND METHODS: The clinical data of 15 Brucella aortic-iliac aneurysm patients who underwent endovascular repair at 2 hospitals from January 2012 to December 2021 were retrospectively collected and analyzed. RESULTS: Fifteen patients (12 men and 3 women) with a mean age of 59.3 years were included. Fourteen patients (93.3%) had a history of exposure to animals (cattle and sheep). All patients had aortic or iliac pseudoaneurysms, 9 abdominal aortic aneurysms (AAAs), 4 iliac aneurysms, and 2 AAA combined with iliac aneurysms. Endovascular aneurysm repair (EVAR) was performed in all patients without conversion to open surgery. Six cases were treated for emergency surgery due to aneurysm rupture. The immediate technique success rate was 100%, with no postoperative death. Two cases had the iliac artery ruptured again after operation because of lack of antibiotic treatment and was given endovascular treatment again. Once brucellosis is diagnosed, antibiotic treatment with doxycycline and rifampicin was initiated for all the patients until 6 months after operation. All patients survived over a median follow-up period of 45 months. Follow-up computed tomography angiography showed that all stent grafts remained patent, with no endoleak. CONCLUSION: EVAR combined with antibiotics treatment is feasible, safe, and effective for Brucella aneurysms and represents a promising treatment option for these Brucella aneurysms. CLINICAL IMPACT: Brucella aneurysms are very rare but life-threatening, and a standard treatment approach has yet to be established. The traditional operation management strategy is surgical resection and debridement of the infected aneurysm and the surrounding tissues. However, open surgical management in these patients causes severe trauma with high surgical risks and mortality (13.3%-40%). We tried to treat Brucella aneurysms with endovascular therapy, and the technique success and survival rate of the operation reached 100%. EVAR combined with antibiotics treatment is feasible, safe, and effective for Brucella aneurysms and represents a promising treatment option for some mycotic aneurysms.

Loss of myeloid Tsc2 predisposes to angiotensin II-induced aortic aneurysm formation in mice.

RATIONALE: Genetic studies have proved the involvement of Tuberous sclerosis complex subunit 2 (Tsc2) in aortic aneurysm. However, the exact role of macrophage Tsc2 in the vascular system remains unclear. Here, we examined the potential function of macrophage Tsc2 in the development of aortic remodeling and aortic aneurysms. METHODS AND RESULTS: Conditional gene knockout strategy combined with histology and whole-transcriptomic analysis showed that Tsc2 deficiency in macrophages aggravated the progression of aortic aneurysms along with an upregulation of proinflammatory cytokines and matrix metallopeptidase-9 in the angiotensin II-induced mouse model. G protein-coupled receptor 68 (Gpr68), a proton-sensing receptor for detecting the extracellular acidic pH, was identified as the most up-regulated gene in Tsc2 deficient macrophages compared with control macrophages. Additionally, Tsc2 deficient macrophages displayed higher glycolysis and glycolytic inhibitor 2-deoxy-D-glucose treatment partially attenuated the level of Gpr68. We further demonstrated an Tsc2-Gpr68-CREB network in macrophages that regulates the inflammatory response, proteolytic degradation and vascular homeostasis. Gpr68 inhibition largely abrogated the progression of aortic aneurysms caused by Tsc2 deficiency in macrophages. CONCLUSIONS: The findings reveal that Tsc2 deficiency in macrophages contributes to aortic aneurysm formation, at least in part, by upregulating Gpr68 expression, which subsequently drives proinflammatory processes and matrix metallopeptidase activation. The data also provide a novel therapeutic strategy to limit the progression of the aneurysm resulting from Tsc2 mutations.

Successful conservative treatment of an isolated inflammatory superior mesenteric artery aneurysm.

Inflammatory superior mesenteric artery aneurysm is an extremely rare but life-threatening condition that can result in fatal rupture. Early surgery has been emphasized to prevent aneurysm rupture. We present a case that was successfully managed with conservative treatment. The patient was treated with intravenous methylprednisolone pulse therapy followed by oral prednisolone. Steroid therapy should be considered for unruptured inflammatory superior mesenteric artery aneurysms before surgery.

Endovascular embolization of spontaneous rupture of isolated splenic artery dissection associated with hemosuccus pancreaticus: a case report.

BACKGROUND: Isolated splenic artery dissection (SAD) is extremely rare, life-threatening, and particularly difficult to diagnose. Moreover, SAD presenting as digestive hemorrhage has not been reported. CASE PRESENTATION: A 44-year-old man presented with recurrent life-threatening hematochezia. Magnetic resonance and computed tomographic angiography showed isolated SAD with an intrapancreatic hematoma. Selective angiography confirmed the diagnosis of rupture of SAD. Hemosuccus pancreaticus was considered the potential mechanism of digestive hemorrhage. It was successfully managed by endovascular coil embolization. CONCLUSIONS: Isolated SAD is especially rare but fatal. Rupture of SAD should be considered in the differential diagnosis as a rare cause of digestive hemorrhage. Endovascular coil embolization is effective in treating ruptured SAD.

Endovascular Stent Graft Repair for True and Post-Traumatic False Aneurysms of the Subclavian Artery.

OBJECTIVE: Subclavian artery aneurysms (SAAs) are uncommon but life-threatening, and a standard treatment approach has yet to be established. The current study aimed to assess the safety and efficacy of endovascular treatment for SAAs. METHODS: The clinical data of 18 SAA patients who underwent endovascular repair at 3 hospitals from January 2009 to December 2019 were retrospectively collected and analyzed. RESULTS: Eighteen patients (12 men and 6 women) with a mean age of 61 years were included. Six patients (33.3%) had a history of hypertension, and 5 (27.8%) had a history of chest trauma. Five patients (27.8%) were asymptomatic. Thirteen (72.2%) SAAs were true aneurysms, and the others (27.8%) were posttraumatic false aneurysms. Endovascular stent graft repair was performed in all patients without conversion to open surgery. The immediate technique success rate was 94.4%, with no postoperative death and only one case (5.6%) of endoleak that was observed on intraoperative angiography and later resolved spontaneously. All patients survived over a median follow-up time of 57 months. Follow-up imaging showed that all stent grafts remained patent, with no endoleak. CONCLUSIONS: Endovascular stent graft repair is feasible, safe, and effective for true and posttraumatic false SAAs and represents a promising treatment option for these SAAs.

Intravenous Leiomyomatosis of the Uterus: A Retrospective Single-Center Study in 14 Cases.

PURPOSE: This study aimed to retrospectively review the diagnosis and surgical treatment of uterine intravenous leiomyomatosis (IVL). METHODS: The clinical data of 14 patients with uterine IVL admitted to our hospital between 2013 and 2018 were retrospectively analyzed, including their demographics, imaging results, surgical procedures, perioperative complications, and follow-up results. RESULTS: The tumors were confined to the pelvic cavity in 7 patients, 1 into the inferior vena cava, 4 into the right atrium, and 2 into the pulmonary artery (including 1 into the superior vena cava). Only one case was misdiagnosed as right atrial myxoma before the operation, which was found during the surgery and was treated by staging surgery; all the other patients underwent one-stage surgical resection. Three patients underwent complete resection of the right atrial tumor through the abdominal incision, and one patient died of heart failure in the process of resection of heart tumor without abdominal surgery. During the 6-60 months of follow-up, 4 patients developed deep venous thrombosis of the lower extremity, and 1 patient developed ovarian vein thrombosis and pulmonary embolism. After anticoagulation treatment, the symptoms disappeared. One patient refused hysterectomy and the uterine fibroids recurred 4 years after the operation. CONCLUSION: Specific surgical plans for uterine IVL can be formulated according to cardiac ultrasound and computed tomography (CT). For the first type of tumor involving the right atrium, the right atrium tumor can be completely removed through the abdominal incision alone to avoid thoracotomy. The disease is at high risk of thrombosis and perioperative routine anticoagulation is required.

Therapeutic management of isolated internal iliac artery aneurysms.

OBJECTIVE: Isolated internal iliac artery aneurysms (IIIAAs) are rare, life-threatening entities for which the optimal treatment strategy has not been established. This study aimed to evaluate the outcomes of open and endovascular treatment of IIIAAs. METHODS: IIIAA cases between January 2009 and March 2019 at two hospitals were retrospectively reviewed. Demographic, clinical, ancillary testing, treatment, and outcome data were collected and analyzed. RESULTS: Forty-two patients (37 men and 5 women) with a mean age of 71 years were included. Twenty-five patients (60%) had a history of hypertension. Twenty-two patients (52%) were asymptomatic, and 16 (38%) presented with abdominal pain (12 with ruptured aneurysms). The 42 included patients had 43 treated IIIAAs. The following surgical techniques were used: surgical resection (n = 6), endovascular coil embolization (n = 12), endovascular stent graft placement across the internal iliac artery origin (n = 8 with 9 aneurysms), and combined coil embolization and stent graft placement (n = 16). The immediate technical success rate was 67%, 67%, and 88% for embolization, stent graft placement, and combined method, respectively. Open surgery was associated with the longest operative time and hospital stay. Overall 30-day mortality was 5% for all patients and 17% for patients with ruptured IIIAAs. Buttock claudication occurred in 7 of 40 patients who survived (18%). The median follow-up time was 56 months. The combined approach was associated with the lowest rates of endoleak (6% vs 25% and 29%) and reintervention (6% vs 17% and 29%) of the three endovascular methods. CONCLUSIONS: Endovascular coil embolization with stent graft placement is a feasible, safe, and effective treatment approach for large IIIAAs without adequate aneurysm necks.

Endovascular treatment of spontaneous renal artery dissection.

OBJECTIVE: This study aimed to assess the outcomes of patients with spontaneous renal artery dissection (SRAD) after endovascular repair. METHODS: We performed a retrospective review of SRAD patients after endovascular treatment between January 2007 and August 2018. Demographic, clinical, ancillary testing, treatment, and outcome data were collected and analyzed. RESULTS: Fourteen patients (12 men and 2 women) with a mean age of 47 years were included in this study. All the patients had hypertension, either new onset (78.6%) or pre-existent (21.4%). Sudden flank pain was the most common symptom. Fourteen patients had 15 affected renal arteries. Endovascular repair was successfully performed in 14 arteries. The technical success rate of endovascular repair was 93.3% (14/15), with no postoperative death. Endovascular repair significantly improved hypertension and renal function, and these improvements persisted during the follow-up period. The effective rate of endovascular repair for improving or curing hypertension was 85.7%. Follow-up imaging showed no sign of stent stenosis or occlusion in those patients who received endovascular repair. CONCLUSIONS: Endovascular repair is safe, feasible, and effective for SRAD treatment and should be a promising alternative to open revascularization.

Expression levels of cathepsin L and cystatin C in a hyperglycemic environment were associated with aortic aneurysm development in a mouse model.

OBJECTIVES: Diabetes mellitus (DM) attenuates the development of aortic aneurysms (AA). This study investigated the expression of cathepsin L and cystatin C in a hyperglycemic environment, and the influence of these proteins on AA development. METHODS: Mice were divided into AA and DM+AA groups ( n=30 per group). DM was induced by injection of streptozotocin; AA was induced by injection of angiotensin II. Doppler examination was used to measure aortic diameter, and Weigert's elastic stain was used to detect elastin degradation. Cathepsin L and cystatin C in aortic tissue were examined by western blotting, immunohistochemistry, and polymerase chain reaction. RESULTS: Aortic diameter in the DM+AA group was less than that in the AA group, and elastin fragmentation grade of the aortic wall was reduced in the DM+AA group. More cathepsin L-positive cells were observed in the AA group than in the DM+AA group; conversely, more cystatin C-positive cells were observed in the DM+AA group than in the AA group. Both protein and mRNA levels of cathepsin L and cystatin C showed similar trends to those observed in immunohistochemistry. CONCLUSIONS: Expression levels of cathepsin L and cystatin C in a hyperglycemic environment were associated with AA development in a mouse model.

Diagnosis and Treatment of Aortic Saddle Embolism.

BACKGROUND: Acute aortic occlusion is a rare but life-threatening medical condition that can result from aortic saddle embolism, thrombosis of an atherosclerotic aorta, or aortic dissection. Herein are described the diagnostic and therapeutic characteristics for a series of patients with aortic saddle embolism. METHODS: A retrospective review of medical records was performed for patients receiving treatment for aortic saddle embolism at a university hospital in China between January 2001 and September 2017. Demographic, clinical, ancillary testing, treatment, and outcome data were collected and analyzed. RESULTS: Eighteen patients (10 women and 8 men) with a mean age of 53.8 years were included. The most commonly associated cardiac diseases were atrial fibrillation or atrial flutter (89%); rheumatic heart disease, valvular heart disease, or both (72%); and congestive heart failure (56%). Rest pain was present in all patients, and sensory or motor deficits were present in 12 patients (67%). Computed tomography (CT) angiography was performed for all patients. Seventeen patients (94%) presented with aortic embolism below the renal arteries. Fifteen patients (83%) underwent bilateral transfemoral embolectomy, and 3 patients (17%) received no intervention. Fasciotomy was performed for 9 patients in 14 limbs. The overall mortality rate was 33%, with a postprocedure mortality rate of 20%. Major morbidity occurred in 60% of patients. Six lower extremities were amputated in 4 patients, and acute renal failure developed in 4 patients. The incidence of postembolectomy internal iliac artery embolism was 58% (11 of 19 iliac arteries), and pelvic ischemia developed in 1 young patient. CONCLUSIONS: Aortic saddle embolism is uncommon but associated with high morbidity and mortality. CT angiography is recommended for diagnosis, and bilateral transfemoral embolectomy is the preferred treatment. Postembolectomy internal iliac artery embolism was common, and prevention of pelvic ischemia should be considered for young patients.

A Modified Loop Snare Technique for Difficult Retrievals of Inferior Vena Cava Filter and Migrated Coil.

The aim of this study was to evaluate the safety and efficacy of a modified loop snare technique for retrieval of difficult inferior vena cava (IVC) filters and migrated coils.A retrospective review of Günther Tulip filter retrievals between January 2014 and February 2017 was performed. A total of 316 IVC filter retrievals were attempted. In 25 cases, the standard technique had failed and our modified loop snare technique was subsequently attempted in 21 of these patients.The retrievals were successful in 20 cases (mean dwell time, 42.6 days, range, 14-102 days). The dwell time of the one failure was 46 days. The retrieval rate increased from 92.1% with the standard technique to 98.4% with the combination of the standard and modified loop snare technique. Unsuccessful retrieval was due to migration and endothelialization of the filter. This technique can also be used to remove migrated coils which cannot be captured by standard techniques. There were no complications from the retrievals.Tilt and endothelialization of filters are the main factors resulting in unsuccessful retrievals with the standard technique. In the present study, we describe an alternative technique for difficult IVC filter retrievals, which can also be used to capture migrated coils and occluders in the aorta and heart.

Endovascular Repair with Periscope Technique for Aortic Dissection with an Aberrant Right Subclavian Artery.

A type B aortic dissection with an aberrant right subclavian artery is an uncommon entity. Most cases have been treated by open or hybrid surgery. We present a case that was managed by endovascular aortic repair with the periscope technique. A thoracic stent graft was implanted into the aortic arch beyond the origin of the right subclavian artery. Two overlapping periscope grafts were placed to maintain perfusion to the right subclavian artery. The presented technique is a feasible and minimally invasive approach for this rare entity.

Blockade of HMGB1 preserves vascular homeostasis and improves blood perfusion in rats of acute limb ischemia/reperfusion.

Acute limb ischemia is one of the most common peripheral arterial disease, while surgical restoration of blood flow often results in ischemia/reperfusion (I/R) injury. Our previous study revealed the inflammation intensity in arterial tissue, characterized by expression of high mobility group box protein 1 (HMGB1), was contrary to the fluctuation of hemodynamics in reperfusion limbs in a rat model. This study meant to clarify the role of HMGB1 during this process. Laser Doppler perfusion imaging evaluated limb hemodynamics in mean and max perfusion unit (PU). Femoral arterial tissue was collected for molecular biology examination. The results revealed that HMGB1 promoted vascular structure remodeling and vasomotor dysfunction during acute I/R, characterized by degradation of collagenous fibers, disruption of elastic lamellae, intensive inflammation and phenotype transfer of smooth muscle cells. Blockade of HMGB1 preserved vascular homeostasis and improved PUs (PmeanPU<0.001, PmaxPU<0.001). The elevated expression of TNF-α, IL-6, ICAM, VCAM, MMP-2, MMP-9, α-SM actin correlated with HMGB1 positively. In conclusion, HMGB1 promoted vascular remodeling and dysfunction via initiating an inflammation cascade during I/R. Blockade of HMGB1 would preserve vascular homeostasis and facilitate the blood perfusion of ischemic limb.

Combined Endovascular Embolization and Open Surgery for Splenic Artery Aneurysm with Arteriovenous Fistula.

Splenic artery aneurysm with arteriovenous fistula is extremely rare; however, it is clinically important because of the potential of aneurysm rupture and gastroesophageal variceal hemorrhage. Most previous cases were managed by surgery directly. We present a case which was successfully treated with combined endovascular embolization and open surgery. It may be a safe and effective approach to manage this entity.