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Background and aims Thrombomodulin (TM), through its lectin-like domain (TMD1), sequesters proinflammatory high-mobility group box 1 (HMGB1) to prevent it from engaging the receptor for advanced glycation end product (RAGE) that sustains inflammation and tissue damage. Our previous study demonstrated that short-term treatment with recombinant TM containing all the extracellular domains (i.e., rTMD123) inhibits HMGB1-RAGE signaling and confers protection against CaCl 2 -induced AAA formation. In this study, we attempted to further optimize TM domains, as a potential therapeutic agent for AAA, using the recombinant adeno-associated virus (AAV) vector. Methods The therapeutic effects of recombinant TMD1 (rTMD1) and recombinant AAV vectors carrying the lectin-like domain of TM (rAAV-TMD1) were evaluated in the CaCl 2 -induced AAA model and angiotensin II-infused AAA model, respectively. Results In the CaCl 2 -induced model, treatment with rTMD1 suppressed the tissue levels of HMGB1 and RAGE, macrophage accumulation, elastin destruction and AAA formation, and the effects were comparable to a mole-equivalent dosage of rTMD123. In the angiotensin II-infused model, a single intravenous injection of rAAV-TMD1 (10 11 genome copies), which resulted in a persistently high serum level of TMD1 for at least 12 weeks, effectively attenuated AAA formation with suppression of HMGB1 and RAGE levels and inhibition of proinflammatory cytokine production, macrophage accumulation, matrix metalloproteinase activities and oxidative stress in the aortic wall. Conclusions These findings corroborate the therapeutic potential of the TM lectin-like domain in AAA. The attenuation of angiotensin II-infused AAA by one-time delivery of rAAV-TMD1 provides a proof-of-concept validation of its application as potential gene therapy for aneurysm development.

Toll-like receptor (TLR) family plays a key role in innate immunity and various inflammatory responses. TLR4, one of the well-characterized pattern-recognition receptors, can be activated by endogenous damage-associated molecular pattern molecules such as high mobility group box 1 (HMGB1) to sustain sterile inflammation. Evidence suggested that blockade of TLR4 signaling may confer protection against abdominal aortic aneurysm (AAA). Herein we aimed to obtain further insight into the mechanism by which TLR4 might promote aneurysm formation. Characterization of the CaCl2-induced AAA model in mice revealed that upregulation of TLR4 expression, localized predominantly to vascular smooth muscle cells (VSMCs), was followed by a late decline during a 28-day period of AAA development. In vitro, TLR4 expression was increased in VSMCs treated with HMGB1. Knockdown of TLR4 by siRNA attenuated HMGB1-enhanced production of proinflammatory cytokines, specifically interleukin-6 and monocyte chemoattractant protein-1 (MCP-1), and matrix-degrading matrix metalloproteinase (MMP)-2 from VSMCs. In vivo, two different strains of TLR4-deficient (C57BL/10ScNJ and C3H/HeJ) mice were resistant to CaCl2-induced AAA formation compared to their respective controls (C57BL/10ScSnJ and C3H/HeN). Knockout of TLR4 reduced interleukin-6 and MCP-1 levels and HMGB1 expression, attenuated macrophage accumulation, and eventually suppressed MMP production, elastin destruction and VSMC loss. Finally, human AAA exhibited higher TLR4 expression that was localized to VSMCs. These data suggest that TLR4 signaling contributes to AAA formation by promoting a proinflammatory status of VSMCs and by inducing proteinase release from VSMCs during aneurysm initiation and development.

Objectives To review our surgical experience of primary infected abdominal aortic aneurysms, with the aim of assessing the safety and durability of in situ prosthetic replacement. Design Retrospective study in a university hospital. Materials and Methods Thirty-four patients who underwent surgery for primary infected abdominal aortic aneurysms over the past 18 years were reviewed. Operative details and outcomes were recorded for analysis. Results There were six suprarenal and 28 infrarenal infections. Salmonellae (18 patients) were the most common pathogens. Thirty patients underwent in situ prosthetic replacement, two underwent extra-anatomic bypass and two underwent endovascular repair. The surgical mortality for overall patients was 18%, and for patients reconstructed in situ , 17%. Among the 30 patients reconstructed in situ , four patients who underwent concomitant gastrointestinal procedures (e.g., repair of the duodenal defect) died. By contrast, 25 of 26 patients without gastrointestinal involvement survived surgery. After a median follow-up period of 58 months, two discharged patients who underwent in situ reconstruction died of late graft infection. Conclusions Our experience suggests that in situ prosthetic replacement can be performed safely with durable outcomes in the majority of patients with infected abdominal aortic aneurysms. Nevertheless, we advise caution when considering this technique with concomitant gastrointestinal procedures.

Background Over-the-wire exchange is a standard treatment for patients with tunneled hemodialysis catheters (THCs) that fail to maintain sufficient extracorporeal blood flow. However, this well-known procedure is unsuitable in the presence of exit-site infection (ESI). In such cases, a modified exchange technique with introduction of the new THC through a remote exit site and the preexisting subcutaneous tunnel may be a solution. Study Design Quality improvement report. Setting & Participants Since 2005, a total of 28 consecutive dysfunctional THCs with ESI in 23 patients who did not have tunnel infection or bacteremia before the procedures was included. Quality Improvement Plan Introduction of the new THC through a remote exit site and preexisting subcutaneous tunnel. Measurements Technical success, perioperative complications, infection rates, and catheter function were recorded for analysis. Results There was only 1 failure, giving an overall technical success rate of 96%. The other 27 exchanged THCs achieved satisfactory flow during subsequent hemodialysis, and the ESI gradually resolved within 2 weeks. Although 8 episodes of new ESI occurred, no subcutaneous tunnel infection or bacteremia occurred within 120 days. Bedridden patients had more occurrences of new ESIs than nonbedridden patients (6 of 9 versus 2 of 13 patients; P = 0.03). Primary catheter patency rates were 100% at 30 days, 82% at 90 days, and 77% at 120 days. Secondary catheter patency rates were 100% at 30 days, 91% at 90 days, and 91% at 120 days. Limitation A small number of cases and comparison with previous studies of THC exchange. Conclusions For dysfunctional THCs with ESI, exchange through remote exit sites and preexisting subcutaneous tunnels is feasible and can be used repeatedly for patients prone to ESI, such as the bedridden. This modified exchange technique is also preferable for operators who question the sterility of previous exit sites and are reluctant to use the over-the-wire technique.

Objectives Patients with rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE) have an increased risk of developing coronary atherosclerosis. However, the impact of RA and SLE on the outcomes in patients undergoing percutaneous coronary intervention (PCI) remains largely underdetermined. Methods Using the National Health Insurance Research Database of Taiwan, we identified 171 547 adult patients who underwent first-time PCI between 2000 and 2010. Among these patients, 525 had established RA, and 211 had SLE. The ORs of inhospital mortality and HRs of overall mortality and adverse cardiac outcomes after PCI (ie, ischaemic events, repeat revascularisation and major adverse cardiac events (MACE)) in relation to RA and SLE were estimated. Results After adjustment for potential confounders, including patient characteristics and procedural variables, RA (OR=1.73, 95% CI 1.11 to 2.68) and SLE (OR=3.81, 95% CI 2.02 to 7.16) were independent predictors of inhospital mortality. In addition, RA was independently associated with overall mortality (HR=1.55, 95% CI 1.35 to 1.79), ischaemic events (HR=1.18, 95% CI 1.01 to 1.39) and MACE (HR=1.20, 95% CI 1.07 to 1.34) during long-term follow-up, whereas SLE was independently associated with overall mortality (HR=2.20, 95% CI 1.74 to 2.78), repeat revascularisation (HR=1.27, 95% CI 1.02 to 1.58) and MACE (HR=1.47, 95% CI 1.24 to 1.75). Compared with patients without autoimmune diseases, patients with more recent SLE-related hospitalisations prior to PCI were at higher risk of inhospital mortality (p for trend Conclusions This study recognises the inherent risks associated with RA and SLE in patients undergoing PCI and highlights the necessity to improve the caring and secondary prevention strategies for these high-risk patients.

Objective— Thrombomodulin (TM), a glycoprotein constitutively expressed in the endothelium, is well known for its anticoagulant and anti-inflammatory properties. Paradoxically, we recently found that monocytic membrane-bound TM (ie, endogenous TM expression in monocytes) triggers lipopolysaccharide- and gram-negative bacteria–induced inflammatory responses. However, the significance of membrane-bound TM in chronic sterile vascular inflammation and the development of abdominal aortic aneurysm (AAA) remains undetermined. Approach and Results— Implicating a potential role for membrane-bound TM in AAA, we found that TM signals were predominantly localized to macrophages and vascular smooth muscle cells in human aneurysm specimens. Characterization of the CaCl 2 -induced AAA in mice revealed that during aneurysm development, TM expression was mainly localized in infiltrating macrophages and vascular smooth muscle cells. To investigate the function of membrane-bound TM in vivo, transgenic mice with myeloid- (LysMcre/TM flox/flox ) and vascular smooth muscle cell–specific (SM22-cre tg /TM flox/flox ) TM ablation and their respective wild-type controls (TM flox/flox and SM22-cre tg /TM +/+ ) were generated. In the mouse CaCl 2 -induced AAA model, deficiency of myeloid TM, but not vascular smooth muscle cell TM, inhibited macrophage accumulation, attenuated proinflammatory cytokine and matrix metalloproteinase-9 production, and finally mitigated elastin destruction and aortic dilatation. In vitro TM-deficient monocytes/macrophages, versus TM wild-type counterparts, exhibited attenuation of proinflammatory mediator expression, adhesion to endothelial cells, and generation of reactive oxygen species. Consistently, myeloid TM–deficient hyperlipidemic mice (ApoE −/− /LysMcre/TM flox/flox ) were resistant to AAA formation induced by angiotensin II infusion, along with reduced macrophage infiltration, suppressed matrix metalloproteinase activities, and diminished oxidative stress. Conclusions— Membrane-bound TM in macrophages plays an essential role in the development of AAA by enhancing proinflammatory mediator elaboration, macrophage recruitment, and oxidative stress.

Keratinocyte-expressed thrombomodulin (TM) and the released soluble TM (sTM) have been demonstrated to promote wound healing. However, the effects of high glucose on TM expression in keratinocytes and the role of TM in diabetic ulcer remain unclear. In this study, we demonstrated that expressions of TM and Toll-like receptor 4 (TLR4) were both downregulated in high-glucose cultured human keratinocytes and in skin keratinocytes of diabetic patients. In addition, the wound-triggered upregulation of TM and sTM production was abolished in both high-glucose cultured human keratinocytes and streptozotocin-induced diabetic mouse skin. Furthermore, supplementation of recombinant sTM could increase TLR4 expression and promote cutaneous wound healing in both high-glucose cultured human keratinocytes and diabetic mice. However, in Tlr4-deleted mice, which exhibited delayed wound healing, the therapeutic benefit of recombinant sTM was abrogated. Moreover, our results showed that tumor necrosis factor-α (TNF-α) expression in keratinocytes was dose-dependently upregulated by glucose, and TNF-α treatment downregulated the expression of TM and TLR4. Taken together, high-glucose environment reduces the expression of TM and TLR4 in keratinocytes possibly through the action of TNF-α, and recombinant sTM can increase the TLR4 expression and promote wound healing under diabetic condition.

Patients with inflammatory rheumatic diseases have an increased risk of developing coronary atherosclerosis. However, outcomes of surgical revascularization in these patients have been rarely studied. We aimed to determine whether, or which, inflammatory rheumatic diseases may pose effects on mortality and adverse cardiac outcomes after coronary artery bypass grafting.By using the National Health Insurance Research Database of Taiwan, we identified 40,639 adult patients who underwent first-time coronary artery bypass grafting between 2000 and 2010. Among these patients, 101 had rheumatoid arthritis, 56 had systemic lupus erythematosus, and 73 had ankylosing spondylitis. The odds ratios (ORs) of operative mortality and hazard ratios (HRs) of overall mortality and adverse cardiac outcomes after coronary artery bypass grafting (ie, myocardial infarction and repeat revascularization) in relation to rheumatoid arthritis, systemic lupus erythematosus, and ankylosing spondylitis were estimated.With adjustment for potential confounders including patient characteristics, hospital levels, and combined surgery, systemic lupus erythematosus was an independent predictor for operative mortality (adjusted OR, 2.63; 95% confidence interval [CI], 1.04-6.65; P = .04) and ankylosing spondylitis was marginally associated with operative mortality (adjusted OR, 2.41; 95% CI, 0.99-5.88; P = .054). Systemic lupus erythematosus was a significantly independent predictor for overall mortality during the follow-up period (adjusted HR, 2.23; 95% CI, 1.51-3.31; P.0001) and might increase the risk of repeat revascularization (adjusted HR, 1.89; 95% CI, 0.97-3.68; P = .06). Neither rheumatoid arthritis nor ankylosing spondylitis was significantly associated with overall mortality and adverse cardiac outcomes.Our study may help surgeons and physicians recognize the potential risks inherent to systemic lupus erythematosus and ankylosing spondylitis when conducting coronary artery bypass grafting and providing follow-up care.

Haemothorax resulting from injury to a great vessel is a potential complication during transvenous pacemaker implantation that can be caused by perforation by the electrode. If the amount of bleeding is massive, control needs thoracotomy. We report on a 70-year-old man who had a massive haemothorax following transvenous pacemaker implantation. This complication was controlled successfully by using positive end-expiratory pressure (PEEP). We conclude that this simple but reproducible experience may offer effective haemostasis for a massive haemothorax caused by transvenous catheter perforation.

Ebstein's anomaly of the tricuspid valve in combination with Tetralogy of Fallot is extremely rare. We report a patient with these combined entities in a baby presented with cyanosis and right heart failure soon after birth. Total correction toward biventricular repair was successfully conducted when he was 7 months old. For management of a patient with such rare complex anomalies, we recommend Carpentier's technique for Ebstein's anomaly to restore the morphology of the right ventricle, and "one and half ventricle repair" can be a salvage procedure if the right ventricle is not functionally tolerant.

The membrane glycoprotein thrombomodulin (TM) has been implicated in keratinocyte differentiation and wound healing, but its specific function remains undetermined. The epidermis-specific TM knockout mice were generated to investigate the function of TM in these biological processes. Primary cultured keratinocytes obtained from TM(lox/lox); K5-Cre mice, in which TM expression was abrogated, underwent abnormal differentiation in response to calcium induction. Poor epidermal differentiation, as evidenced by downregulation of the terminal differentiation markers loricrin and filaggrin, was observed in TM(lox/lox); K5-Cre mice. Silencing TM expression in human epithelial cells impaired calcium-induced extracellular signal-regulated kinase pathway activation and subsequent keratinocyte differentiation. Compared with wild-type mice, the cell spreading area and wound closure rate were lower in keratinocytes from TM(lox/lox); K5-Cre mice. In addition, the lower density of neovascularization and smaller area of hyperproliferative epithelium contributed to slower wound healing in TM(lox/lox); K5-Cre mice than in wild-type mice. Local administration of recombinant TM (rTM) accelerated healing rates in the TM-null skin. These data suggest that TM has a critical role in skin differentiation and wound healing. Furthermore, rTM may hold therapeutic potential for the treatment of nonhealing chronic wounds.

Computed tomography (CT) is the modality of choice in the diagnosis of mycotic aneurysms. The present study aimed to classify the CT findings of mycotic aneurysms, and to assess their predictive value based on the correlation of a CT-based grading system with prognostic factors and outcomes. Over the past 21 years, 40 consecutive patients underwent open surgery for mycotic aneurysms of the abdominal aorta and iliac arteries in our hospital. The CT appearances of mycotic aneurysms were categorized into four grades: grade 1, periarterial changes without destruction of the arterial wall; grade 2, presence of saccular outpouching; grade 3, extensive retroperitoneal infection; and grade 4, massive perianeurysmal hemorrhage. Clinical data were recorded for analysis. The surgical mortality and overall aneurysm-related mortality rates were 17.5 and 25 %, respectively. The poor prognostic predictors were shock, rupture, and concomitant gastrointestinal procedures. The increasing proportions of shock and rupture status corresponded to mycotic aneurysms of higher grades in the CT-based grading. In addition, one patient in grades 1 and 2, versus five in grades 3 and 4 (P = 0.02), required concomitant gastrointestinal procedures. The CT-based grading exhibited a strong association with surgical mortality (Cramer’s V coefficient = 0.65; P = 0.002) and a relatively strong association with overall aneurysm-related mortality (Cramer’s V coefficient = 0.53; P = 0.01). For patients surgically treated for abdominal mycotic aneurysms, the CT-based grading is correlated with clinical severity, surgical complexity, and outcomes, and thus it may serve as a simple scale for risk classification.

A secondary aortoenteric fistula (SAEF) is relatively rare after abdominal aortoiliac reconstructive surgery. Most SAEFs are associated with a graft prosthesis, and rectum involvement is rarely reported. We report a rectal SAEF after aortoiliac aneurysmorrhaphy, i.e., oversewing the artery without a graft. A 62-year-old man had an appendicitis-related infected right common iliac artery aneurysm and sterile left aortoiliac arterial aneurysm. Six weeks after an appendectomy with a right iliac aneurysmectomy, left aortoiliac reduction aneurysmorrhaphy, and femorofemoral bypass grafting, he developed repeated bloody stool. Abdominal computed tomography and colonoscopy findings strongly indicated communication between the native aortic or iliac arteries and the rectal lumen. Emergency surgery—left infected aortoiliac artery excision, oversewing the aortic stump, right axillofemoral bypass, and sigmoid protectomy with an end-colostomy—was performed. Unfortunately, the aortic stump developed a pseudoaneurysm 6 weeks after the second laparotomy. During the third emergency laparotomy, more of the stump was amputated and wrapped in the omentum. At 45-month follow-up, the patient was well and without infection recurrence or leg ischemia. This case is a reminder that even patients without a graft prosthesis are at risk for SAEF after any aortoiliac surgery. We also comprehensively reviewed the English literature from 1960 to 2008 on prosthesis-free SAEF patients.

Iatrogenic injury is an underreported but potentially devastating complication of orthopedic wire migration. We report a 48-year-old man with a tracheoinnominate artery fistula caused by migration of a Kirschner wire that was inserted for fixation of a left clavicle fracture nine years before. Following surgical removal of the wire and repair of both trachea and innominate artery, the patient recovered eventually. Although migration of orthopedic wire to the trachea has been reported twice in previous literature, such a complication involving both the trachea and arch vessel was not previously described. Physicians who care for patients with orthopedic wires in place should be aware of migration with tracheoinnominate artery fistula and other iatrogenic injuries as potentially lethal complications.

Ruptured abdominal aortic aneurysm is a true emergency for emergency physicians and surgeons. Achieving effective proximal control may ameliorate further hemodynamic deterioration and buy time for patients awaiting further repair. An 82-year-old man was referred to our hospital with shock resulting from a ruptured abdominal aortic aneurysm. At the moment of impending cardiac arrest, aortic occlusion was achieved with a transfemoral endovascular balloon, without fluoroscopic guidance. The octogenarian then underwent a prosthetic graft reconstruction and recovered well. In this report, the safeguards and pitfalls of aortic occlusion using an endovascular balloon are discussed. This procedure is not only effective in vascular control but also valuable in resuscitation.

Persistent sciatic artery (PSA) is a rare congenital malformation. In the early embryonic stage, the sciatic artery is the major blood supply for the lower limb bulb and is later replaced by the iliofemoral artery as the limb develops. Its failure to regress, sometimes associated with femoral arterial hypoplasia, and therefore becoming the dominant inflow to the lower extremity is called PSA. This anomaly is often associated with a higher rate of aneurysm formation or thromboembolic complications causing lower extremity ischemia. Here, we describe a 79-year-old male patient who presented with acute left lower extremity ischemia. He was treated initially with conventional embolectomy through inguinal and popliteal incisions. The bilateral PSA with thrombosed aneurysms was not identified at first on computed tomographic angiography. It was later diagnosed intraoperatively due to the discontinuity of the superficial femoral artery and popliteal artery found with embolectomy catheter, and was managed successfully with ePTFE graft bypass. Careful interpretation of the imaging study may be helpful in preoperative diagnosis.

Expression of CD44 and its isoforms has been demonstrated to be a prognostic marker in many neoplasms. Gastrointestinal neuroendocrine tumor is a slow-growing neoplasm, whose behavior is determined by site of occurrence, size or specific histologic growth pattern. In this study, the feasibility of using CD44 as a prognostic marker in gastrointestinal neuroendocrine tumor is evaluated.Representative paraffin-embedded sections of gastrointestinal neuroendocrine tumor from 22 patients were studied by immunohistochemical staining using monoclonal antibodies against CD44, Ki-67, and p53 retrospectively. The correlation between these markers and clinical behavior of the tumors was analyzed.Positive expression of CD44 was observed in 15 cases (68%) of gastrointestinal neuroendocrine tumor. Expression of CD44 showed significant inverse correlation with lymph node status (P=0.049), distant metastasis (p0.001) and mortality (p=0.002). Neither p53 nor Ki-67 correlated with lymph node status, distant metastasis and overall survival. Both lymph node status and distant metastasis showed strong correlation to survival after multivariate analysis. Patients with the tumor growing from the hindgut had better survival (p=0.024). The patients with stronger CD44 immunoreactivity (or = 2+) tumors had significantly favorable survival (p=0.004) compared with those with weaker immunoreactivity (or = 1+) tumors.Expression of CD44 in gastrointestinal neuroendocrine tumor inversely correlates with tumor metastasis, associates with a favorable outcome and may serve as one of the prognostic indicators.

We report a case of rat bite fever caused by Streptobacillus moniliformis in Taiwan. It manifested as prosthetic valve endocarditis, which was cured by cardiac valve replacement and antimicrobial therapy. The DNA sequence of the 16S rRNA gene of S. moniliformis was detected in valve specimens by PCR and nucleotide sequencing.

La survenue d’une fistule aorto-digestive secondaire (FADS) est relativement rare apres chirurgie reparatrice de l’aorte abdominale. La plupart de FADS sont associes a une greffe prothetique et l’atteinte du rectum est rarement rapportee. Nous rapportons un cas de FADS rectale apres anevrysmorraphie aortoiliaque, c.-a-d., restauration de l’artere sans greffe. Un homme de 62 ans a presente un anevrysme iliaque commun droit infectes lie a une appendicite et un anevrysme aorto-iliaque gauche sterile. Six semaines apres l’appendicectomie avec resection de l’anevrysme iliaque droit, un anevrysmorraphie aorto-iliaque gauche de reduction et pontage croise interfemoral prothetique, il a developpe des hemorragies digestives a repetition. Le scanner abdominal et la coloscopie ont objective une communication entre l’aorte ou les arteres iliaques indigenes et la lumiere rectale. Un traitement chirurgical a ete pratique en urgence: excision de l’anevrysme aorto-iliaque gauche infecte, suture du moignon aortique, pontage axillo-femoral droit et resection recto-sigmoidienne avec colostomie terminale. Malheureusement, le moignon aortique a developpe un faux anevrysme 6 semaines apres la deuxieme laparotomie. Lors de la troisieme laparotomie en urgence, la plus grosse partie du moignon aortique a ete resequee et couverte par une epiplooplastie. Au suivi a 45 mois, le patient etait en bon etat general et sans recidive d’infection ou d’ischemie de membre. Ce cas montre que meme les patients sans greffe prothetique sont a risque de developper une FADS apres n’importe quelle chirurgie aortoiliaque. Nous egalement avons revu la litterature en anglais de 1960 a 2008 sur les patients ayant presente une FADS en l’absence de greffe prothetique.