Presence of Helicobacter cinaedi in Atherosclerotic Abdominal Aortic Aneurysmal Wall.

Recently, the relationship between Helicobacter cinaedi (H. cinaedi) infection and several diseases, including cardiovascular and central nervous system disorders, bone and soft tissue disorders, and infectious abdominal aortic aneurysms (AAAs), has been reported. Moreover, H. cinaedi may be associated with arteriosclerosis. In the present study, we investigated the association between H. cinaedi infection and clinically uninfected AAAs. Genetic detection of H. cinaedi in the abdominal aneurysm wall was attempted in 39 patients with AAA undergoing elective open surgery between June 2019 and June 2020. DNA samples extracted from the arterial wall obtained during surgery were analyzed using nested polymerase chain reaction (PCR). The target gene region was the H. cinaedi-specific cytolethal distending toxin subunit B (cdtB). Nine (23.1%) of 39 patients showed positive bands corresponding to H. cinaedi, and further sequencing analyses demonstrated the presence of H. cinaedi DNAs in their aneurysm walls. In contrast, all the non-aneurysm arterial walls in our patients were negative for H. cinaedi. In conclusion, this is the first report of the detection of H. cinaedi in the walls of a clinically non-infectious AAA.

Successful Treatment of Giant Common and Proper Hepatic Artery Aneurysm Complicating Autosomal Dominant Polycystic Kidney Disease.

Hepatic artery aneurysms (HAAs) complicating autosomal dominant polycystic kidney disease (ADPKD) are extremely rare. On account of the large number of renal cysts in ADPKD, ingenuity is required to safely perform surgery for HAA. Here, we present the case of a 60-year-old man with a common and proper HAA of >60 mm complicated with ADPKD. In this patient, difficulty in maintaining the field of view was expected during surgery. Hence, we performed a hybrid approach with celiac-to-right hepatic artery bypass by puncturing the femoral artery and cannulating the splenic artery to allow celiac-splenic artery balloon occlusion in case of rupture. More than 5 years postoperatively, the graft is patent without intervention.

Detection of Macrophage Localization in the Abdominal Aortic Aneurysm Wall Using Ex Vivo Superparamagnetic Iron Oxide-Enhanced Magnetic Resonance Imaging.

BACKGROUND: Macrophages in the aneurysmal wall play an important role in the pathogenesis of abdominal aortic aneurysms (AAAs). Superparamagnetic iron oxide (SPIO) is a macrophage-specific contrast agent that results in negative enhancement on magnetic resonance imaging (MRI). SPIO-enhanced MRI targeting the intraluminal thrombus of AAAs has been previously reported. However, macrophages in the media and adventitia of AAA wall have not been investigated in detail. This study aimed to evaluate macrophage localization using SPIO-enhanced MRI in the media and adventitia of AAA wall, as macrophages play a crucial role in AAA pathogenesis. METHODS: Here, we included study and control patients planning to undergo open surgery for AAA. The study patients received SPIO injection 2 days preoperatively (the SPIO group, n = 7), whereas the control patients did not receive this injection (the control group). Ex vivo MRI was performed on the harvested AAA wall in the SPIO group during the surgery. The concordance between the number of macrophages and berlin blue (BB)-stained areas was histologically evaluated in both groups. Moreover, the concordance between regions of interest in MR images and BB-stained areas was evaluated. RESULTS: The proportion of BB-stained macrophages was higher in the SPIO group (0.93; interquartile range [IQR], 0.83-0.95) than in the control group (0.03; IQR, 0.026-0.11) (P < 0.05), indicating uptake of SPIO by macrophages in the AAA wall. A significant positive correlation was found between the number of BB-stained macrophages and BB-stained areas using Kendall rank correlation coefficient in the SPIO group (τ = 0.58; P < 0.05). Significant correlations were found in the distributions of the region of interest of SPIO-enhanced MRI and BB-stained areas in the media and adventitia in 5 of 7 patients. CONCLUSIONS: Macrophages present in the media and adventitia of the AAA wall showed an uptake of the SPIO contrast agent injected 2 days prior, which were then detected by ex vivo MRI. This suggests that SPIO-enhanced MR images help detect the localization of macrophages on the AAA wall, indicating its potential to serve as a novel index for AAA pathogenesis.

Oral Steroid Use and Abdominal Aortic Aneurysm Expansion　- Positive Association.

BACKGROUND: The maximum axial diameter (MAD) of a fusiform abdominal aortic aneurysm (AAA) is an indicator of the risk of expansion or rupture. Apart from smoking and MAD itself, few expansion risk factors have been reported. In this study, we investigated expansion risk factors for AAA.Methods and Results:This retrospective cohort study included 176 patients who attended Tohoku University Hospital with infrarenal fusiform AAA. AAA expansion rate was determined on multidetector computed tomography, and the correlations between expansion rate and the clinical data were analyzed. The median expansion rate was 2.405 mm/year. On univariate analysis, a significant positive correlation with expansion rate was observed for the initial MAD (P<0.001) and significant negative correlations for oral angiotensin receptor blocker usage (P=0.025), height (P=0.005), body weight (P=0.017), total cholesterol (P=0.007), low-density lipoprotein cholesterol (P=0.004), and HbA1c (P=0.037). On logistic regression analysis, significant positive associations with expansion rate were observed for initial MAD (P<0.001) and oral steroid usage (P=0.029) and a negative association for height (P=0.041). CONCLUSIONS: Oral steroid usage is an important risk factor for AAA expansion, independent of other risk factors of atherosclerosis and MAD.

Histological Analysis of a New Route after Subintimal Crural Angioplasty.

BACKGROUND: Subintimal angioplasty is an alternative approach in treating critical limb ischemia with crural artery disease. However, route or location of the newly created channel is not understood. CASE PRESENTATION: A 68-year-old man was referred to our hospital with ischemic gangrene of the right big toe. We performed endovascular treatment because he was a poor candidate for bypass surgery. The posterior tibial artery was treated using subintimal angioplasty, although it resulted in early occlusion. We decided that he was not able to receive any further limb salvage treatment and performed amputation below the knee 7 days after treatment. The specimen from the origin of posterior tibial artery to plantar artery bifurcation was resected and the formalin-fixed vessel was cut into 39 segments. Histological analysis showed that the newly formed lumen was comparatively well dilated and created in the media by tearing internal elastic lamina in almost the whole of its length. The severely poor runoff vessels below the ankle were thought to be a main cause of early occlusion. CONCLUSIONS: The newly formed lumen by subintimal crural angioplasty could be well dilated and created in the media.

A novel, potent dual inhibitor of Arg-gingipains and Lys-gingipain as a promising agent for periodontal disease therapy.

The periodontal pathogen Porphyromonas gingivalis produces a unique class of cysteine proteinases termed gingipains that comprises Arg-gingipain (Rgp) and Lys-gingipain (Kgp). Growing evidence indicates that these 2 types of gingipains synergistically contribute to the entire virulence of the organism and increase the risk of periodontal disease (PD) by disrupting the host immune system and degrading the host tissue and plasma proteins. Therefore, a dual inhibitor of both gingipains would have attractive clinical potential for PD therapy. In this study, a novel, potent, dual inhibitor of Rgp and Kgp was developed through structure-based drug design, and its biological potency was evaluated in vitro and in vivo. This inhibitor had low nanomolar inhibitory potency (Ki=40 nM for Rgp, Ki=0.27 nM for Kgp) and good selectivity for host proteases and exhibited potent antibacterial activity against P. gingivalis by abrogating its manifold pathophysiological functions. The therapeutic potential of this inhibitor in vivo was also verified by suppressing the vascular permeability that was enhanced in guinea pigs by the organism and the gingival inflammation in beagle dog PD models. These findings suggest that a dual inhibitor of Rgp and Kgp would exhibit noteworthy anti-inflammatory activity in the treatment of PD.

Sudden cardiac arrest immediately after stent graft deployment during treatment of iliac aneurysm with iliocaval fistula.

An 84-year-old woman with heaviness of the right lower extremity had an iliocaval fistula related to a right internal iliac aneurysm. Immediately after deployment of an endovascular device, cardiac arrest occurred because of severely decreased sympathetic activity. After surgery, the patient recovered well and has been followed up with exclusion of the arteriovenous fistula and resolution of the type II endoleak. Endovascular treatment for large arteriovenous fistulas induces rapid closure of the fistula together with restoration of blood supply to the lower extremity. Markedly deactivated sympathetic nerve traffic could result in a critical hemodynamic status in association with endograft deployment.

Distal Bypass Improves Skin Perfusion Pressure at the Whole Foot Regardless of Angiosomes in Patients with Chronic Limb-Threatening Ischemia.

Objectives: Distal bypass surgery's effect on tissue blood pressure beyond a focal angiosome remains debated. This study assessed tissue blood pressure in both direct revascularized angiosome (DRA) and indirect revascularized angiosome (IRA) after bypass surgery, utilizing repeated skin perfusion pressure (SPP) measurements. Methods: Twenty-nine limbs in 27 chronic limb-threatening ischemia (CLTI) patients (22 males and five females, age: 70.2 ± 9.3 years) who received distal bypass surgery were enrolled. SPP measurements were conducted for the DRA and IRA at 10 time intervals, encompassing both preoperative and postoperative periods of every 3-5 days until 30 days. Results: In total, 486 SPP measurements were collected from 58 measurement sites, and the transition of the SPP at the DRA was 35.4-62.5-59.5-70.2-58.2-62.2-63.1-63.6-63.8-73.4 mmHg and IRA was 29.4-53.4-53.7-58.8-51.3-63.1-47.9-62.1-57.6-61.0 mmHg. No significant differences were observed between SPP at the DRA and IRA. Fifteen wounds on the DRA (63%) and five on the IRA (100%) healed. Conclusion: Distal bypass improves SPP in both direct and IRAs of CLTI patients. These data indicated distal bypass improves tissue blood flow at entire foot regardless of angiosomes.

Extracorporeal shock wave therapy improves the walking ability of patients with peripheral artery disease and intermittent claudication.

BACKGROUND: Despite the recent advances in bypass surgery and catheter interventional therapy for peripheral artery disease (PAD), the long-term outcome of revascularization therapy for infrapopliteal lesions remains unsatisfactory. We have previously demonstrated that low-energy extracorporeal shock wave (SW) therapy effectively induces neovascularization through upregulation of angiogenic factors and improves myocardial ischemia in pigs and humans and in hindlimb ischemia in rabbits. In this study, we thus examined whether our SW therapy also improves the walking ability of patients with PAD and intermittent claudication. METHODS AND RESULTS: We treated 12 patients (19 limbs) in Fontaine II stage (males/females, 10/2; 60-86 years old) with low-energy SW therapy to their ischemic calf muscle 3 times/week for 3 consecutive weeks. After 24 weeks, the pain and distance subscale scores of the walking impairment questionnaire were significantly improved (33±25 vs. 64±26, 27±16 vs. 64±23, respectively, both P<0.01). Maximum walking distance was also significantly improved at 4 weeks (151±37% from baseline, P<0.01) and was maintained at 24 weeks (180±74% from baseline, P<0.01). Moreover, the recovery time of the tissue oxygenation index in the calf muscle during a treadmill test, which reflects local O2 supply, was significantly shortened (295±222s vs. 146±137s, P<0.01). Importantly, no adverse effects were noted. CONCLUSIONS: Non-invasive SW therapy improves the walking ability of PAD patients.

Anticoagulation Therapy for Pregnancy-Associated Thrombosis: A Retrospective Observational Study.

Objectives: Pregnancy-associated deep vein thrombosis (DVT) is a rare disease, and data on anticoagulation therapy are lacking. The present study examined the treatment outcome with unfractionated heparin (UFH) subcutaneous injection in patients with pregnancy-associated DVT. Methods: This single-center, retrospective, observational study enrolled 15 patients with pregnancy-associated DVT treated from January 2014 to April 2021. Results: The median age was 35 years. The median gestation week at onset was 10 (interquartile range is 8-11). All patients presented with painful symptoms with edema. All patients had proximal DVT. Anticoagulation therapy using UFH was performed in 14 patients. The median continuous dose of heparin was 18,750 U/day, and the median subcutaneous dose was 20,000 U/day. During the outpatient period, the values of activated partial thromboplastin time fluctuated wildly, but the fibrin monomer complex level remained consistently low. There were two mild bleeding complications, but neither prevented the continuation of anticoagulation therapy. During delivery, thrombi were not detected in 10 of 13 patients (77%), whereas three patients (23%) exhibited regression without resolution of the thrombus. Conclusion: Anticoagulation using UFH subcutaneous injection was safely performed in patients with pregnancy-associated DVT without serious complications or progression of thrombosis.

Inflammatory popliteal aneurysm.

A 67-year-old man was referred to our department because of fever, right lower thigh swelling, and redness with pain. Laboratory tests showed slightly elevated leukocytes and markedly elevated C-reactive protein levels. Computed tomography confirmed a popliteal aneurysm with wall thickening, so-called mantle sign. Aneurysmorrhaphy with a reversed autologous saphenous vein reconstruction was performed. Aneurysm sac and perianeurysm tissue cultures were negative for aerobic and anaerobic bacteria. The microscopic appearance of the aneurysm showed thickening of the adventitia and infiltration of inflammatory cells. This report presents, for the first time, findings suggestive of an inflammatory aneurysm of the popliteal artery.

Long-term outcome of partial resection in venous adventitial cystic disease.

Venous adventitial cystic disease is extremely rare. Therefore, standard treatment methods have not been clearly defined. Some reports suggest that complete cyst removal is an effective treatment. However, considering the relatively high recurrence rate, follow-up periods were short. Herein, we report the case of a 75-year-old man with venous adventitial cystic disease successfully treated with partial cyst wall excision. No recurrence was observed for 10 years postoperatively. This case suggests that complete cyst wall excision might not be necessary for the treatment of venous adventitial cystic disease.

In Situ Revascularization with a Rifampicin-Soaked Prosthesis to Treat Bare Iliac Artery Stent Infection: A Case Report.

Bare stent infection is an extremely rare complication of endovascular treatment. In such cases, surgical resection of the infected bare stent and revascularization are recommended; however, the revascularization strategy remains controversial. We present a case of a 78-year-old man with an infected aneurysm caused by a bare iliac artery stent infection. We resected the infected aneurysm and performed in situ anatomic reconstruction using a rifampicin-soaked prosthesis with omental coverage. The patient had no reinfection at the 3-year follow-up. Therefore, this procedure may be a useful treatment for bare iliac artery stent infections.

Long-Term Outcomes of Surgical Treatment by In Situ Graft Reconstruction for Infected Abdominal Aortic Aneurysm.

Objectives: The optimal surgical management for primary infected abdominal aortic aneurysm (IAAA) is controversial. Here, we report the early and long-term results of surgical treatments with the resection of the IAAA and in situ graft reconstruction with pedicled omental coverage that was performed at out hospital. Methods: Between 2010 and 2017, 27 consecutive patients (26 males, 1 female, median age 69 years) with IAAA were surgically treated with the resection of the IAAA, in situ graft reconstruction and covered with a pedicled omental flap. Perioperative and long-term outcomes were reviewed retrospectively by medical records. Results: Clinical manifestations, including pyrexia, fever and abdominal pain, were observed during the treatment of the patients. Aneurysm excision and in situ graft reconstruction with omental coverage were performed for all cases. In 13 cases (48.1%), tissue culture was positive. The antibiotic was administered intravenously for 9 to 47 days (median 18 days) postoperatively, and after confirming the reduction of the inflammatory response, it was administered as oral agents for 24 to 443 days (median 169 days).There was no perioperative death or re-infection. Perioperative complications were found in 8 cases (29.6%) of minor spinal cord infarction, ileus, chylous ascites, and cholangitis due to choledochlithiasis. During the observation period of median 1,147 days, there was no recurrence of infection, graft infection, or disease-related death. There were six deaths due to other diseases. And the overall survival rate was 76.2%. Conclusion: According to our study, the long-term outcomes of surgical treatment with in situ graft reconstruction for IAAA were considered satisfactory. (This is a translation of Jpn J Vasc Surg 2019; 28: 35-40.).

Long-Term Outcomes of Acute Limb Ischemia: A Retrospective Analysis of 93 Consecutive Limbs.

Objective: To examine the medium- to long-term outcomes of acute limb ischemia (ALI), which are unclear at present. Methods: We analyzed 93 consecutive limbs in 77 patients with ALI between January 2005 and December 2015 treated at our vascular center. We categorized the cases into four groups according to etiology (embolism, thrombosis, graft thrombosis, and dissection groups) to assess survival, limb salvage, and freedom from re-intervention rates. Results: The mean age at onset was 72±15 years. The median follow-up length was 2.90 years. The Rutherford categories I, IIa, IIb, and III included 1, 38, 51, and 3 cases, respectively. Thromboembolectomy was performed in all patients in the embolism and thrombosis groups. In addition, endovascular treatment was performed in 25 (37.3%) patients, especially in the thrombosis group (81.3%). A major amputation could not be avoided in 10 patients. The 5-year limb salvage rates for categories IIa and IIb were 97.1% and 83.1%, respectively. The 5-year freedom from re-intervention rate was 89.2%. The survival rates at 1, 3, and 5 years were 87.9%, 75.2%, and 60.6%, respectively. Conclusion: The 5-year survival rates of patients with ALI were equivalent to those with chronic limb threatening ischemia (CLTI). The intervention and long-term outcomes were distinguishable according to etiology.

Natural History and Chronological Growth Rate of Renal Artery Aneurysms.

Objective: Renal artery aneurysm (RAA) is an uncommon disease, the natural course of which is still not well known. The objective of this study is to define factors that affect the growth rate of RAAs. Materials and Methods: We retrospectively reviewed 32 aneurysms in 26 patients at our institute between January 2010 and March 2016. Basal demographics, comorbidities, reason for diagnosis, and details of the aneurysms and interventions were recorded. The chronological changes in the diameter of the RAA using multiplanar reconstructions of computed tomography images were measured and analyzed. Results: The baseline mean diameter was 20.1±8.4 mm (range: 9.9-41). The mean follow-up period was 3.13±2.1 y (range: 0.5-7.1). The median growth rate was 0.35 mm/y (interquartile range: 0.05, 0.62). The growth rate was slower when the initial diameter was <20 mm than when it was >20 mm (p=0.036). Also, whole-completed calcification was a significant factor for slower growth (p=0.016). We performed ex-vivo surgery in two cases and coil packing with stenting in one. No ruptures occurred during the study period. Conclusion: Our results suggest that cases with an RAA diameter <20 mm do not require intervention. The interval period can be longer in whole-completed calcification types.

Selective proteolysis of apolipoprotein B-100 by Arg-gingipain mediates atherosclerosis progression accelerated by bacterial exposure.

Epidemiological studies suggest the association of periodontal infections with atherosclerosis, however, the mechanism underlying this association remains poorly understood. Porphyromonas gingivalis is the primary etiologic agent of adult periodontitis and produces a unique class of cysteine proteinases consisting of Arg-gingipain (Rgp) and Lys-gingipain (Kgp). To elucidate key mechanisms for progression of atherosclerosis by P. gingivalis infection, we tested the effects of the disruption of genes encoding Rgp and/or Kgp and inhibitors specific for the respective enzymes on atherosclerosis progression in apolipoprotein E-knockout mice. Repeated intravenous injection of wild-type P. gingivalis resulted in an increase in atherosclerotic lesions as well as an increase in the serum LDL cholesterol and a decrease of HDL cholesterol in these animals. LDL particles in P. gingivalis-injected animals were modified as a result of selective proteolysis of apoB-100 in LDL particles. This modification of LDL by P. gingivalis resulted in an increase in LDL uptake by macrophages and consequent foam cell formation in vitro. The atherosclerotic changes induced by P. gingivalis infection were attenuated by disruption of Rgp-encoding genes or by an Rgp-specific inhibitor. Our results indicate that degradation of apoB-100 by Rgp plays a crucial role in the promotion of atherosclerosis by P. gingivalis infection.

Long-Term Outcomes of Surgical Treatment with In Situ Graft Reconstruction for Secondary Aorto-Enteric Fistula.

Objectives: The optimal surgical management for secondary aorto-enteric fistula (sAEF) is controversial. Here, we report the long-term outcomes of a surgical treatment with in situ graft reconstruction for sAEF that was performed at our hospital. Methods: Between 2009 and 2012, 10 consecutive patients (8 males, 2 females, mean age 75.9 years) with sAEF were surgically treated with in situ graft reconstruction. Perioperative and long-term outcomes were reviewed retrospectively by medical records. Results: Clinical manifestations, including gastrointestinal bleeding, shock, sepsis, and back and abdominal pain, were observed during the treatment of the patients. In all the cases, the fistula was found between the duodenum or small intestine and the graft anastomosis, the graft itself, or pseudoaneurysm. Total graft excision and in situ graft reconstruction with omental coverage and digestive tract reconstruction was performed for all cases. There were two operative deaths because of multiple organ dysfunction syndrome and sepsis. The other patients showed no sAEF related complications, such as graft infection, and were alive during the 54-month mean follow-up period (33-76 months). Conclusion: According to our study, the long-term outcomes of surgical treatment with in situ graft reconstruction for sAEF were considered satisfactory. (This article is a translation of Jpn J Vasc Surg 2016; 25: 1-6.).

Surgical resection and inferior vena cava reconstruction for treatment of the malignant tumor: technical success and outcomes.

OBJECTIVE: The purpose of this study was to review patients who underwent inferior vena cava (IVC) resection with concomitant malignant tumor resection and to consider the operative procedures and the outcomes. MATERIALS AND METHODS: Between 2000 and 2012, 41 patients underwent resection of malignant tumors concomitant with surgical resection of the IVC at our institute. The records of these patients were retrospectively reviewed. RESULTS: Primary tumor resections included nephrectomy, hepatectomy, retroperitoneal tumor extirpation, lymph node dissection, and pancreaticoduodenectomy. The IVC interventions were partial resection in 23 patients and total resection in 18 patients. Four patients underwent IVC replacement. Operation-related complications included pulmonary embolism, acute myocardial infarction, deep vein thrombosis, leg edema and temporary hemodialysis. There were no operative deaths. The mean follow-up period was 24.9 months (range: 2-98 months). The prognosis depended on the type and stage of the tumor. CONCLUSION: Resection and reconstruction of the IVC can be performed safely if the preoperative evaluations and surgical procedures are performed properly. The IVC resection without reconstruction was permissive if the IVC was completely obstructed preoperatively, but it may also be considered in cases where the IVC is not completely obstructed.

Nitroglycerin-mediated vasodilatation of the brachial artery may predict long-term cardiovascular events irrespective of the presence of atherosclerotic disease.

AIM: Nitroglycerin-mediated vasodilatation (NMD) provides insight into the NTG-induced bioactivity of smooth muscle. It is plausible that in dysfunctional smooth muscle cells, the response to nitroglycerin may become blunted. The relationship between impaired brachial artery NMD and subsequent cardiovascular events is not well established. METHODS: We examined brachial artery flow-mediated dilatation (FMD) and NMD using ultrasound in 93 subjects (71±7 years, including 26 with peripheral artery disease (PAD), 37 with aortic aneurysms, 10 with PAD complicated with aneurysms, and 20 without evident arterial disease). Brachial artery responses to hyperemia and nitroglycerin were measured every minute after cuff deflation and nitroglycerin administration. Time courses of vasodilatation were assessed and maximal FMD and NMD were measured. RESULTS: The time courses in response to NTG were sigmoidal and maximal diameter reached 7.2±1.6 minutes after NTG was administered sublingually. The mean FMD was 2.3±2.0% and the mean NMD was 17.6±7.1%. Subjects were prospectively followed for an average of 47±13 months. Eighteen subjects had an event during follow-up; events included myocardial infarction (five), unstable angina pectoris (four), stroke (two), aortic dissection (one), ruptured aortic aneurysm (three), symptomatic abdominal aortic aneurysm (two), and lower limb ischemia requiring revascularization (one). NMD and FMD were significantly lower in subjects with events than in those without an event. In a Cox proportional-hazards model, lower FMD as well as lower NMD independently predicted future cardiovascular events. CONCLUSION: Brachial artery nitroglycerin-mediated vasodilatation may add information to conventional risk stratification.