Publications by authors named "Taeseung Lee"

65 Publications

Paraplegia after Open Repair of Suprarenal Abdominal Aortic Aneurysm.

Vasc Specialist Int 2020 Dec;36(4):248-251

Department of Surgery, Seoul National University Bundang Hospital, Seongnam, Korea.

Spinal cord ischemia after open repair of abdominal aortic aneurysm (AAA) is an unpredictable and devastating complication. We present a case report of a patient who developed paraplegia 6 hours after open repair of suprarenal AAA. A 74-yearold man presented with asymptomatic 5.5-cm suprarenal AAA, for which he underwent open repair under general anesthesia. The paraplegia was identified 6 hours after the operation. Postoperative magnetic resonance imaging showed T2 signal hyperintensity and swelling of the spinal cord, which were consistent findings with subacute spinal cord infarction. Although intravenous steroid was administered and lumbar cerebral spinal fluid drainage was instituted, his neurological outcome did not improve. He was discharged after vigorous rehabilitation but still has paraplegia and requires wheelchair for ambulation.
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http://dx.doi.org/10.5758/vsi.200078DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7790699PMC
December 2020

Clinical Manifestations of Symptomatic Spontaneous Dissection of the Celiac and Superior Mesenteric Arteries.

Vasc Specialist Int 2020 Dec;36(4):224-232

Department of Surgery, Seoul National University Bundang Hospital, Seongnam, Korea.

Purpose: Spontaneous isolated dissection of the celiac artery (SID-CA) and superior mesenteric artery (SID-SMA) are rare vascular diseases with similar presentation, yet comparative studies have not been reported. In this study, we compared their characteristics with the aim of providing insights into their etiology.

Materials And Methods: Patients diagnosed with symptomatic SID-CA and SIDSMA between July 2009 and December 2018 were included. Demographics, clinical presentation, radiologic findings, treatment strategies, and outcomes were analyzed.

Results: Twenty-one patients with SID-CA and 40 patients with SID-SMA were compared. Demographics and initial abdominal pain characteristics were similar, but pain severity was significantly higher and associated mean fasting time was significantly longer in patients with SID-CA than in those with SID-SMA (fasting time 3.2 vs 2.1 days, P=0.001). Most patients were successfully treated conservatively without recurrent pain or aneurysmal dilatation, but 33.3% patients with SID-CA and 17.5% with SID-SMA required endovascular intervention. More favorable remodeling in terms of dissection regression on follow-up computed tomography was found after stenting, where patients with SID-CA showed better remodeling than those with SID-SMA. The overall median follow-up period was 22-31 months, while for patients with stent insertion, it was 55-77 months, and no stent occlusions were found during this period.

Conclusion: Patients with SID-CA presented with severer and longer-duration abdominal pain than those with SID-SMA. Stenting in both groups showed good long-term patency and favorable remodeling, with a higher regression rate for SIDCA. Based on our results, patients with SID-CA may benefit more from active endovascular intervention.
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http://dx.doi.org/10.5758/vsi.200071DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7790695PMC
December 2020

Erratum to "Re Mid to Long Term Outcomes in Management of Spontaneous Isolated Coeliac Artery Dissection" [European Journal of Vascular & Endovascular Surgery 60 (1) (2020) 151-152].

Eur J Vasc Endovasc Surg 2020 Oct 17;60(4):638. Epub 2020 Aug 17.

Department of Surgery, Seoul National University Bundang Hospital, Seoul National University College of Medicine, South Korea. Electronic address:

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http://dx.doi.org/10.1016/j.ejvs.2020.07.049DOI Listing
October 2020

Re "Mid to Long Term Outcomes in Management of Spontaneous Isolated Coeliac Artery Dissection".

Eur J Vasc Endovasc Surg 2020 07 2;60(1):151-152. Epub 2020 Jun 2.

Department of Surgery, Seoul National University Bundang Hospital, Seoul National University College of Medicine, South Korea. Electronic address:

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http://dx.doi.org/10.1016/j.ejvs.2020.02.010DOI Listing
July 2020

CASS (CyanoAcrylate closure versus Surgical Stripping for incompetent saphenous veins) study: a randomized controlled trial comparing clinical outcomes after cyanoacrylate closure and surgical stripping for the treatment of incompetent saphenous veins.

Trials 2020 Jun 3;21(1):460. Epub 2020 Jun 3.

Department of Surgery, Seoul Metropolitan Government-Seoul National University Boramae Medical Center, Seoul National University College of Medicine, 07061 20 Boramae-ro, Dongjak-gu, Seoul, South Korea.

Background: Several modalities are used for the treatment of varicose veins. Open surgical treatment with ligation and stripping of the saphenous vein has been the standard of care for many years. Endovenous thermal ablation has been shown to be a safe and effective alternative with high, long-term, target-vein closure rates. Despite this, there is the possibility of thermal injury to surrounding structures. The recently introduced cyanoacrylate closure is also considered to be a good alternative and the risk of injury to surrounding structures is minimal. The purpose of this study is to demonstrate the non-inferiority of cyanoacrylate closure with the VenaSeal™ closure system compared to surgical stripping in terms of clinical outcomes for the treatment of incompetent great saphenous veins.

Methods/design: This is an open-label, multicenter, prospective, randomized controlled trial evaluating the non-inferior clinical outcomes of cyanoacrylate closure compared to surgical stripping for the treatment of incompetent saphenous veins. After baseline measurements, participants will be randomly allocated into either the cyanoacrylate closure group or the surgical-stripping group. The primary endpoint of the study is the complete closure rate of the target vein in the cyanoacrylate closure group, and the absence of venous reflux or residual venous tissue after surgical stripping in the surgical-stripping group. These endpoints will be measured by Doppler ultrasound performed by qualified vascular technologists or investigators at 3 months after treatment. Secondary outcomes include perioperative pain, postoperative ecchymosis, clinical assessment (including general and disease-specific quality of life evaluations), complete closure rate, and absence of venous reflux or residual venous tissue at the 12- and 24-month follow-ups, as well as all adverse event rates during the 24-month follow-up period.

Discussion: This multicenter randomized controlled trial is designed to show non-inferiority in terms of complete closure rate of cyanoacrylate compared to surgical stripping for the treatment of incompetent saphenous veins.

Trial Registration: Clinical Research Information Service (CRIS), ID: KCT0003203. Registered on 20 September 2018.
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http://dx.doi.org/10.1186/s13063-020-04393-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7268719PMC
June 2020

Rivaroxaban after Thrombolysis in Acute Iliofemoral Venous Thrombosis: A Randomized, Open-labeled, Multicenter Trial.

Sci Rep 2019 12 30;9(1):20356. Epub 2019 Dec 30.

Seoul National University Hospital, Seoul, South Korea.

Recently non-Vitamin K antagonist oral anticoagulants (NOAC) is replacing warfarin for the treatment of deep vein thrombosis (DVT). However, the role of NOAC after thrombolysis of acute iliofeomral DVT (IFDVT) is not yet defined. This randomized clinical trial aimed to compare the safety and efficacy of rivaroxaban versus warfarin after catheter directed thrombolysis of an IFDVT. Patients with acute DVT of both the iliac and the femoral vein (n = 72) were recruited and randomized to either standard anticoagulation (enoxaparin and warfarin, n = 35) or rivaroxaban (n = 37) after successful thrombolysis or mechanical thrombectomy. Primary efficacy outcome was a recurrence of any venous thromboembolism (VTE) within 6 months. Secondary safety outcomes included major bleeding, clinically relevant non-major bleeding (CRNMB), other adverse event, and all-cause mortality. Rate of recurrent VTE were similar in both groups (11.4% versus 12.5%; p = 0.94). Major bleeding or CRNMB was less in rivaroxaban group without significance (2.9% versus 9.4%, HR, 0.31; 95% CI, 0.03-2.96; p = 0.31). Recurrence-free survival and major bleeding-free survival at 6 months were not different in both groups. After thrombolysis of acute IFDVT, rivaroxaban was as safe and effective as warfarin in preventing DVT recurrence.
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http://dx.doi.org/10.1038/s41598-019-56887-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6937283PMC
December 2019

Mid- to Long-Term Outcomes in Management of Spontaneous Isolated Coeliac Artery Dissection (SICAD).

Eur J Vasc Endovasc Surg 2020 Feb 5;59(2):247-253. Epub 2019 Dec 5.

Department of Surgery, Seoul National University Bundang Hospital, Seongnam, Republic of Korea; College of Medicine, Seoul National University, Seoul, Republic of Korea. Electronic address:

Objective: Spontaneous Isolated Coeliac Artery Dissection (SICAD) is a rare disease with few reports of management strategies. This study reports the mid- to long-term outcomes of conservative management and endovascular intervention of SICAD treatment.

Methods: Sixteen patients presenting with symptomatic SICAD from September 2006 to October 2018 were reviewed retrospectively. The clinical manifestations, initial radiological findings, methods of treatment, and serial follow up studies were analysed.

Results: The mean age of the patients was 51.2 ± 7.9 years, with a median follow up of 33.3 (range 1.0-118.9) months. Four patients received early intervention because of aneurysmal dilatation or distal hypoperfusion. Four patients who received conservative management showed progression of disease and were recommended for delayed intervention. Although collaterals prevented further hepatic ischaemia, one of these four patients failed in delayed intervention because of extensive thrombi completely occluding the hepatic artery. In the remaining eight patients who were managed conservatively, three (37.5%) showed regression of disease, one (12.5%) showed partial regression, and five (62.5%) showed no change in intimal flap or thrombosis, but all had symptomatic improvement. The median follow up duration for the seven patients who underwent successful intervention was 77.3 (range 34.3-118.9) months, and all stenting remained patent during the follow up period.

Conclusion: Early intervention in symptomatic SICAD patients may be necessary in over 50% of patients, and endovascular stenting has durable long term outcomes.
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http://dx.doi.org/10.1016/j.ejvs.2019.09.510DOI Listing
February 2020

DEL-1 ameliorates high-fat diet-induced insulin resistance in mouse skeletal muscle through SIRT1/SERCA2-mediated ER stress suppression.

Biochem Pharmacol 2020 01 25;171:113730. Epub 2019 Nov 25.

Department of Pharmacology, College of Medicine, Chung-Ang University, Seoul, Republic of Korea.

Inflammation and endoplasmic reticulum (ER) stress are associated with the development of insulin resistance and diabetes. Developmental endothelial locus-1 (DEL-1) enhances efferocytosis by macrophage and suppresses inflammatory response. However, effects of DEL-1 on ER stress-mediated insulin resistance in skeletal muscle remain unclear. Here, DEL-1 treatment augmented SIRT1 expression in C2C12 myocytes, thereby increasing SERCA2 expression in a dose-dependent fashion, and attenuated ER stress and insulin resistance under palmitate treatment condition. SIRT1/SERCA2 knockdown abrogated effects of DEL-1 on palmitate-induced insulin resistance as well as ER stress. Pharmacological significance of DEL-1 was confirmed by in vivo experiments. DEL-1 administration suppressed ER stress, insulin resistance, and SIRT1/SERCA2 expression in skeletal muscle of high-fat diet (HFD)-fed mice. Additionally, siRNA transfection-mediated in vivo downregulation of SIRT1 suppressed the effects of DEL-1 on expression of SERCA2, ER stress, and insulin resistance in skeletal muscle of HFD-fed mice. DEL-1 attenuates palmitate-induced and HFD-induced skeletal muscle ER stress and insulin resistance via SIRT1/SERCA2-mediated signaling.
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http://dx.doi.org/10.1016/j.bcp.2019.113730DOI Listing
January 2020

Successful Treatment of Life-Threatening Small Bowel Bleeding With Thalidomide After Living Donor Kidney Transplantation: A Case Report.

Transplant Proc 2019 Nov 14;51(9):3092-3098. Epub 2019 Oct 14.

Department of Surgery, Seoul National University Bundang Hospital, Seongnam, Korea; Department of Surgery, Seoul National University College of Medicine, Seoul, Korea. Electronic address:

Gastrointestinal bleeding after kidney transplantation is a complication that can occur from immunosuppressant use. We present a case of refractory small bowel bleeding treated successfully with thalidomide after multiple failed attempts of conventional treatment. A 65-year-old male patient with diabetic nephropathy underwent living donor kidney transplantation. The surgery was uneventful, however, he developed immunosuppressant-induced melena with unstable vital signs 11 days later. There were a total of 4 bleeding episodes until the 90th postoperative day, and he received a total of 290 units of red blood cell transfusion during this period. Endoscopic clipping, transarterial embolization, and 2 surgical interventions failed to stop the bleeding. A trial of thalidomide 100 mg per day finally stopped the bleeding and the patient was discharged on the 110th postoperative day with a functioning renal graft. This case shows that thalidomide can be a safe option to treat immunosuppressant-induced refractory gastrointestinal bleeding in the setting of kidney transplantation. Additionally, this is the first case that reports the survival of a renal graft after more than 3000 mL of transfusion.
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http://dx.doi.org/10.1016/j.transproceed.2019.07.009DOI Listing
November 2019

Kynurenic acid attenuates pro-inflammatory reactions in lipopolysaccharide-stimulated endothelial cells through the PPARδ/HO-1-dependent pathway.

Mol Cell Endocrinol 2019 09 15;495:110510. Epub 2019 Jul 15.

Department of Pharmacology, College of Medicine, Chung-Ang University, Seoul, Republic of Korea. Electronic address:

Kynurenic acid (KA) regulates energy homeostasis and alleviates inflammation in adipose tissue but how KA affects the atherosclerotic response in HUVECs remains unclear. We evaluated the effects of KA on lipopolysaccharide (LPS)-induced inflammation and apoptosis in HUVECs. KA enhanced peroxisome proliferator-activated receptor delta (PPARδ) expression in HUVECs and THP-1 cells and suppressed LPS-induced atherosclerotic responses through PPARδ-mediated signaling. Moreover, KA treatment mitigated LPS-induced phosphorylation of nuclear factor kappa B and pro-inflammatory cytokine release in HUVECs and THP-1 cells, and down-regulated adhesion molecules in HUVECs and adhesion of THP-1 cells to HUVECs following LPS treatment. KA treatment decreased LPS-induced inflammation and apoptosis, and also promoted heme oxygenase (HO)-1 expression, which suppresses inflammation in HUVECs. Suppression of PPARδ or HO-1 expression markedly mitigated the effects of KA on atherosclerotic responses in HUVECs. Thus, KA attenuates LPS-induced atherosclerotic responses by suppressing inflammation via the PPARδ/HO-1-dependent pathway.
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http://dx.doi.org/10.1016/j.mce.2019.110510DOI Listing
September 2019

Access site pseudoaneurysms after endovascular intervention for peripheral arterial diseases.

Ann Surg Treat Res 2019 Jun 29;96(6):305-312. Epub 2019 May 29.

Department of Surgery, Seoul National University Bundang Hospital, Seongnam, Korea.

Purpose: Pseudoaneurysms after percutaneous vascular access are common and potentially fatal if left untreated. The aim of this study was to determine the incidence and risk factors associated with access site pseudoaneurysms after endovascular intervention for peripheral arterial disease (PAD) under a routine postintervention ultrasound (US) surveillance protocol.

Methods: A total of 254 PAD interventions were performed in a single center between January 2015 and November 2016, and puncture site duplex US surveillance was routinely performed within 48 hours of the procedure. Clinical, procedural and follow-up US data were analyzed.

Results: The overall incidence of pseudoaneurysm was 2.75% (6 cases in the femoral artery and 1 in the brachial artery). There was no difference between retrograde and antegrade approach, but there was a higher rate of pseudoaneurysm formation after manual compression compared to arterial closure device (ACD) use (4.3% vs. 0.87%). Manual compression was more commonly used for antegrade punctures (79.0%) and ACD for retrograde punctures (67.7%). Calcification was more frequently found in antegrade approach cases (46.8% vs. 16.9% for retrograde cases) and manual compression was preferred in its presence. All pseudoaneurysms were treated successfully at the time of diagnosis by US-guided compression repair and there were no cases of rupture.

Conclusion: Pseudoaneurysm rates after therapeutic endovascular intervention for PAD were comparable to other cardiologic or interventional radiologic procedures despite the higher possibility of having a diseased access vessel. Routine US surveillance of access sites allowed for early diagnosis and noninvasive treatment of pseudoaneurysms, preventing potentially fatal complications.
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http://dx.doi.org/10.4174/astr.2019.96.6.305DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6543050PMC
June 2019

Salsalate ameliorates the atherosclerotic response through HO-1- and SIRT1-mediated suppression of ER stress and inflammation.

Inflamm Res 2019 Aug 29;68(8):655-663. Epub 2019 May 29.

Department of Surgery, Seoul National University Bundang Hospital, Seoul National University College of Medicine, Seongnam, 13620, Korea.

Objective And Design: Inflammation plays a causative role in atherosclerosis development. Salsalate is an anti-inflammatory drug used to treat atherosclerosis, but the mechanisms by which it affects atherosclerotic progression remain unclear.

Methods: Human umbilical vascular endothelial cells (HUVECs) and THP-1 human monocytes were treated with salsalate. Heme oxygenase 1 (HO-1) and sirtuin 1 (SIRT1) small interfering RNAs (siRNAs) were used to suppress each gene expression. Protein analyses were performed for measuring the expression of HO-1, SIRT1, nuclear factor kappa B (NFκB), cell adhesion molecules, and endoplasmic reticulum (ER) stress markers. Furthermore, cell adhesion assay, caspase 3 activity assay, and ELISA were also performed.

Results: In this study, we show that salsalate increases the expression of HO-1 and SIRT1 in HUVEC and suppresses lipopolysaccharide (LPS)-induced atherosclerotic responses via HO-1- and SIRT1-mediated pathways. Salsalate treatment of HUVEC and THP-1 cells reduced LPS-induced phosphorylation of NFκB and secretion of the proinflammatory cytokines TNFα and MCP-1. Salsalate treatment of HUVEC reduced the expression of the adhesion molecules ICAM, VCAM, and E-selectin and the LPS-induced adhesion of THP-1 cells to HUVEC. Salsalate treatment also attenuated LPS-induced ER stress and cell apoptosis. These anti-atherosclerotic effects were reversed by treating cells with siRNA for HO-1 and SIRT1.

Conclusions: Salsalate ameliorates LPS-induced atherosclerotic reactions via HO-1 and SIRT1-dependent reduction of inflammation and ER stress. Activation of these pathways by salsalate may provide therapeutic strategies for treating atherosclerosis.
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http://dx.doi.org/10.1007/s00011-019-01248-6DOI Listing
August 2019

Implementation of a resident night float system in a surgery department in Korea for 6 months: electronic medical record-based big data analysis and medical staff survey.

Ann Surg Treat Res 2019 May 24;96(5):209-215. Epub 2019 Apr 24.

Department of Surgery, Seoul National University Bundang Hospital, Seongnam, Korea.

Purpose: To evaluate superiority of a night float (NF) system in comparison to a traditional night on-call (NO) system for surgical residents at a single institution in terms of efficacy, safety, and satisfaction.

Methods: A NF system was implemented from March to September 2017 and big data analysis from electronic medical records was performed for all patients admitted for surgery or contacted from the emergency room (ER). Parameters including vital signs, mortality, and morbidity rates, as well as promptness of response to ER calls, were compared against a comparable period (March to September 2016) during which a NO system was in effect. A survey was also performed for physicians and nurses who had experienced both systems.

Results: A total of 150,000 clinical data were analyzed. Under the NO and NF systems, a total of 3,900 and 3,726 patients were admitted for surgery. Mortality rates were similar but postoperative bleeding was significantly higher in the NO system (0.5% 0.2%, P = 0.031). From the 1,462 and 1,354 patients under the NO and NF systems respectively, that required surgical consultation from the ER, the time to response was significantly shorter in the NF system (54.5 ± 70.7 minutes 66.8 ± 83.8 minutes, P < 0.001). Both physicians (90.4%) and nurses (91.4%) agreed that the NF system was more beneficial.

Conclusion: This is the first report of a NF system using big data analysis in Korea, and potential benefits of this new system were observed in both ward and ER patient management.
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http://dx.doi.org/10.4174/astr.2019.96.5.209DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6483933PMC
May 2019

Asprosin impairs insulin secretion in response to glucose and viability through TLR4/JNK-mediated inflammation.

Mol Cell Endocrinol 2019 04 7;486:96-104. Epub 2019 Mar 7.

Department of Pharmacology, College of Medicine, Chung-Ang University, Seoul, South Korea. Electronic address:

Severe inflammation in the islets is observed in obese patients with type 2 diabetes. Inflammation in the islets is caused by obesity-induced serum free fatty acids. Asprosin is a fasting-induced adipokine, which contributes to hepatic glucose production. However, the effects of asprosin on inflammation and cellular dysfunction in pancreatic β-cells remain to be elucidated. Here, we demonstrated that treatment of mouse insulinoma MIN6 cells and human primary islets containing β-cells with palmitate increased asprosin expression and secretion. Treatment of MIN6 cells and human primary islets with palmitate increased phosphorylation of the inflammatory marker nuclear factor-kappa B (NFκB) and the release of pro-inflammatory cytokines including TNF and MCP-1 and decreased glucose-stimulated insulin secretion and cell viability. However, siRNA-mediated suppression of asprosin reversed these changes. Recombinant asprosin treatment of MIN6 cells and human primary islets augmented the inflammation response, cellular dysfunction, and apoptosis in a dose-dependent manner. Asprosin induced toll-like receptor (TLR) 4 expression and JNK phosphorylation. siRNA for TLR4 or JNK mitigated the effects of asprosin on inflammation and cellular dysfunction. These results suggest that palmitate-derived asprosin secretion from β-cells results in their inflammation and dysfunction through a TLR4/JNK-mediated pathway. This report suggests asprosin as a novel therapeutic target for the treatment of type 2 diabetes through preservation of β-cell function.
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http://dx.doi.org/10.1016/j.mce.2019.03.001DOI Listing
April 2019

Treatment options for isolated iliac artery aneurysms and their impact on aortic diameter after treatment.

Ann Surg Treat Res 2019 Mar 26;96(3):146-151. Epub 2018 Feb 26.

Divison of Vascular Surgery, Department of Surgery, Seoul National University Bundang Hospital, Seongnam, Korea.

Purpose: Isolated iliac artery aneurysm (IIAA) is uncommon. It is frequently treated by endovascular aneurysm repair (EVAR). This study was to evaluate treatment results of IIAA and survey aortic diameter after EVAR.

Methods: Patients treated for IIAA in Seoul St. Mary's Hospital and Bundang Seoul National University from 2005 to April 2016 were retrospectively enrolled. The inclusion criteria of IIAA was >30 mm of iliac artery aneurysm without abdominal aortic aneurysm, which was treated by open surgical repair (OSR) or EVAR. Patients' clinical characteristics, treatment results, and mortality were obtained from electronic medical records. Diameters of aorta and iliac arteries were measured periodically with scheduled interval based on CT scans.

Results: Forty-nine patients (40 males; mean age, 71.9 ± 11.1 years) were enrolled. Five ruptured IIAAs were treated with EVAR (n = 1) or hybrid methods (n = 4). The diameter of ruptured IIAAs was 65 ± 31.4 mm, which was not significantly different from that of elective (44.3 ± 17.0 mm). Forty-four elective IIAA underwent 9 OSR, 31 EVARs, and 3 hybrid treatments (15 bifurcated and 12 straight stent-grafts). Treatment success rate was 93.8% without hospital mortality. There were 4 type I endoleak, 1 type II endoleak, and 1 type III endoleak without aneurysm-related mortality during follow-up. However, the aortic diameter was increased over time though there was no change or decrease in common iliac artery's diameter.

Conclusion: Treatment of IIAA included various endovascular modalities as well as open surgery. Regular surveillance is still needed due to aortic dilatation after its treatment.
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http://dx.doi.org/10.4174/astr.2019.96.3.146DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6393409PMC
March 2019

Early experiences of endovascular aneurysm repair for ruptured abdominal aortic aneurysms.

Ann Surg Treat Res 2019 Mar 26;96(3):138-145. Epub 2018 Feb 26.

Department of Surgery, Seoul National University Bundang Hospital, Seoul National University College of Medicine, Seongnam, Korea.

Purpose: The use of endovascular aneurysm repair (EVAR) for ruptured abdominal aortic aneurysms (r-AAA) is steadily increasing. We report early experiences of EVAR for r-AAA performed in two tertiary referral centers in Korea.

Methods: We retrospectively reviewed r-AAA patients treated by EVAR from May 2013 to December 2017. An EVAR-first strategy for r-AAA was adopted whenever feasible. The demographic information, anatomic characteristics, operative details, postoperative complications with special attention to abdominal compartment syndrome (ACS), and 30-day mortality were collected and analyzed.

Results: We identified 13 patients who underwent EVAR for r-AAA. Mean age was 74.2 years and mean AAA size was 74.2 mm. Two patients underwent cardiopulmonary resuscitation at initial presentation. Bifurcated stent grafts were used in 12 out of 13 cases and physician-modified endografts with fenestrated/chimney techniques were performed in 2 cases with short neck. Successful stent graft deployment was achieved in all cases. Three patients were suspected of having ACS and 2 of them underwent laparotomy for decompression. The 30-day mortality was 7.7% (1 of 13), the only mortality being a patient that refused decompressive laparotomy for suspected ACS.

Conclusion: Despite the small numbers, the outcomes of EVAR for treatment of r-AAA were very promising, even in selected cases with unfavorable anatomy. These outcomes were achieved by a dedicated and well-trained team approach, and by use of high-end angiographic technology. Finally, ACS after EVAR is not uncommon, and requires a high index of suspicion as well as liberal use of decompressive surgery.
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http://dx.doi.org/10.4174/astr.2019.96.3.138DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6393412PMC
March 2019

Use of Self-Assembling Peptides to Enhance Stem Cell Function for Therapeutic Angiogenesis.

Stem Cells Int 2018 13;2018:4162075. Epub 2018 Jun 13.

Department of Surgery, Seoul National University College of Medicine, Seoul, Republic of Korea.

The use of nanomaterials for biomedical applications has become a promising field in regenerative medicine. Self-assembling peptides (SAPs) have been proposed as a good candidate because they are able to self-assemble into stable hydrogels and interact with cells or molecules when combined together. This in turn can lead to the improved survival or action of cells or molecules to obtain the desired effects. In this study, we investigated whether the combination of mesenchymal stem cells (MSCs) with SAPs could improve angiogenesis in ischemic hindlimbs of rats compared to MSC or SAP treatment alone. The combination of MSCs and SAPs showed an overall higher expression of angiogenesis markers on fluorescent immunohistochemical analysis and a lower degree of fibrosis and cell apoptosis, which in turn led to an overall tendency for improved perfusion of the ischemic hindlimbs. Finally, SAPs also showed the ability to recruit endogenous host MSCs into the site of action, especially when modified to incorporate substance P as a functional motif, which when injected with exogenous MSCs, allowed for the dual presence of MSCs at the site of action. Overall, these results suggest that SAPs can be applied with stem cells to potentiate angiogenesis, with potential therapeutic application in vascular diseases.
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http://dx.doi.org/10.1155/2018/4162075DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6020535PMC
June 2018

Maresin 1 attenuates pro-inflammatory reactions and ER stress in HUVECs via PPARα-mediated pathway.

Mol Cell Biochem 2018 Nov 3;448(1-2):335-347. Epub 2018 Jul 3.

Department of Pharmacology, College of Medicine, Chung-Ang University, 221, Heuksuk-dong, Dongjak-gu, Seoul, 156-756, Republic of Korea.

The current study was designed to investigate the therapeutic effects of Maresin 1 (MAR1) on atherosclerotic response. Human monocytes THP-1 and human umbilical vein endothelial cells (HUVECs) were used to investigate the effects of MAR1 on lipopolysaccharide (LPS)-induced inflammation and apoptosis. In this study, we found that MAR1 induces peroxisome proliferator-activated receptor alpha (PPARα) expression. We also demonstrated that MAR1 suppresses atherosclerotic reactions caused by LPS treatment via a PPARα-dependent pathway. MAR1 treatment inhibited LPS-induced phosphorylation of nuclear factor kappa B (NF-κB) and secretion of pro-inflammatory cytokines in HUVECs and THP-1 cells. In HUVEC cells, expression of adhesion molecules and LPS-stimulated adhesion of THP-1 cells to the endothelium were significantly decreased after MAR1 treatment. Furthermore, LPS-induced endoplasmic reticulum (ER) stress and cell apoptosis was significantly decreased after MAR1 treatment of HUVECs. MAR1 also led to a dose-dependent increase in oxygen-regulated protein 150 (ORP150) expression which is responsible for the inhibition of ER stress. Notably, all of the pro-atherosclerotic effects were completely abrogated by treatment with small interfering (si) RNA targeting PPARα. In conclusion, MAR1 ameliorates LPS-induced atherosclerotic reactions via PPARα-mediated suppression of inflammation and ER stress.
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http://dx.doi.org/10.1007/s11010-018-3392-yDOI Listing
November 2018

Chitinase-3-like protein 1 ameliorates atherosclerotic responses via PPARδ-mediated suppression of inflammation and ER stress.

J Cell Biochem 2018 08 8;119(8):6795-6805. Epub 2018 May 8.

Department of Surgery, Seoul National University Bundang Hospital, Seoul National University College of Medicine, Seongnam, Korea.

Chitinase 3-like protein 1 (CHI3L1) is a novel biomarker of systemic inflammation. However, the effects of CHI3L1 on the progression of atherosclerosis remain to be explored. In the current study, we found that CHI3L1 induces peroxisome proliferator-activated receptor delta (PPARδ) expression, leading to a dose-dependent increase in oxygen-regulated protein 150 (ORP150) expression. We demonstrated that CHI3L1 suppresses atherosclerotic reactions caused by LPS treatment via a PPARδ-dependent pathway. Treatment of HUVECs and THP-1 cells with CHI3L1 suppressed LPS-induced phosphorylation of nuclear factor kappa B (NFκB) and secretion of proinflammatory cytokines such as TNFα and MCP-1. In HUVECs, expression of adhesion molecules and LPS-stimulated adhesion of THP-1 cells to the endothelium were significantly reduced after CHI3L1 treatment. Furthermore, LPS-induced endoplasmic reticulum (ER) stress and cell apoptosis were significantly ameliorated after treatment of HUVECs with CHI3L1. Particularly, all of the pro-atherosclerotic effects were significantly mitigated by treatment with small interfering (si) RNA for PPARδ. In conclusion, CHI3L1 ameliorates LPS-induced atherosclerotic reactions via PPARδ-mediated suppression of inflammation and ER stress.
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http://dx.doi.org/10.1002/jcb.26873DOI Listing
August 2018

β-aminoisobutyric acid attenuates LPS-induced inflammation and insulin resistance in adipocytes through AMPK-mediated pathway.

J Biomed Sci 2018 Mar 28;25(1):27. Epub 2018 Mar 28.

Department of Surgery, Seoul National University Bundang Hospital, Seoul National University College of Medicine, 166 Gumi-ro, Bundang-gu, Seongnam, 463-707, Korea.

Background: β-aminoisobutyric acid (BAIBA) is produced in skeletal muscle during exercise and has beneficial effects on obesity-related metabolic disorders such as diabetes and non-alcoholic fatty liver disease. Thus, it is supposed to prevent high fat diet (HFD)-induced inflammation and insulin resistance in adipose tissue though anti-inflammatory effects in obesity. Previous reports have also demonstrated strong anti-inflammatory effects of BAIBA.

Methods: We used BAIBA treated fully differentiated 3T3T-L1 mouse adipocytes to investigate the effects of exogenous BAIBA on inflammation and insulin signaling in adipocytes. Insulin signaling-mediated proteins and inflammation markers were measured by Western blot analysis. Secretion of pro-inflammatory cytokines were measured by ELISA. Lipid accumulation in differentiated 3 T3-L1 cells was stained by Oil red-O. Statistical analysis was performed by ANOVA and student's t test.

Results: BAIBA treatment suppressed adipogenesis assessed by adipogenic markers as well as lipid accumulation after full differentiation. We showed that BAIBA treatment stimulated AMP-activated protein kinase (AMPK) phosphorylation in a dose-dependent manner and lipopolysaccharide (LPS)-induced secretion of pro-inflammatory cytokines such as TNFα and MCP-1 was abrogated in BAIBA-treated 3 T3-L1 cells. Treatment of 3 T3-L1 cells with BAIBA reduced LPS-induced NFκB and IκB phosphorylation. Furthermore, BAIBA treatment ameliorated LPS-induced impairment of insulin signaling measured by IRS-1 and Akt phosphorylation and fatty acid oxidation. Suppression of AMPK by small interfering (si) RNA significantly restored these changes.

Conclusions: We demonstrated anti-inflammatory and anti-insulin resistance effects of BAIBA in differentiated 3 T3-L1 cells treated with LPS through AMPK-dependent signaling. These results provide evidence for the beneficial effects of BAIBA not only in liver and skeletal muscle cells but also in adipose tissue.
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http://dx.doi.org/10.1186/s12929-018-0431-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5875012PMC
March 2018

CTRP9 Regulates Growth, Differentiation, and Apoptosis in Human Keratinocytes through TGFβ1-p38-Dependent Pathway.

Mol Cells 2017 Dec 16;40(12):906-915. Epub 2017 Nov 16.

Department of Surgery, Seoul National University Bundang Hospital, Seoul National University College of Medicine, Seongnam 13620, Korea.

Impairment of wound healing is a common problem in individuals with diabetes. Adiponectin, an adipocyte-derived cytokine, has many beneficial effects on metabolic disorders such as diabetes, obesity, hypertension, and dyslipidemia. C1q/TNF-Related Protein 9 (CTRP9), the closest paralog of adiponectin, has been reported to have beneficial effects on wound healing. In the current study, we demonstrate that CTRP9 regulates growth, differentiation, and apoptosis of HaCaT human keratinocytes. We found that CTRP9 augmented expression of transforming growth factor beta 1 (TGFβ1) by transcription factor activator protein 1 (AP-1) binding activity and phosphorylation of p38 in a dose-dependent manner. Furthermore, siRNA-mediated suppression of TGFβ1 reversed the increase in p38 phosphorylation induced by CTRP9. siRNA-mediated suppression of TGFβ1 or p38 significantly abrogated the effects of CTRP9 on cell proliferation and differentiation while inducing apoptosis, implying that CTRP9 stimulates wound recovery through a TGFβ1-dependent pathway in keratinocytes. Furthermore, intravenous injection of CTRP9 via tail vein suppressed mRNA expression of Ki67 and involucrin whereas it augmented TGFβ1 mRNA expression and caspase 3 activity in skin of type 1 diabetes animal models. In conclusion, our results suggest that CTRP9 has suppressive effects on hyperkeratosis, providing a potentially effective therapeutic strategy for diabetic wounds.
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http://dx.doi.org/10.14348/molcells.2017.0097DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5750709PMC
December 2017

Validation of the Korean version of the walking impairment questionnaire in patients with peripheral arterial disease.

Ann Surg Treat Res 2017 Aug 28;93(2):103-109. Epub 2017 Jul 28.

Department of Surgery, Seoul National University College of Medicine, Seoul, Korea.

Purpose: Intermittent claudication is the most common early symptom of peripheral arterial occlusive disease. Walking impairment questionnaire (WIQ) is a short, inexpensive, easy-to-complete questionnaire to assess intermittent claudication and can provide data of usual walking. The purpose of this study is to validate the new Korean version of WIQ.

Methods: Total 51 patients with claudication were enrolled. While 4 patients were dropped out, 47 patients with claudication into were divided groups based on the treatment received: surgery (n = 33) and medication (n = 14). The surgery group was subdivided into the bypass (n = 13) and intervention (n = 20) groups. WIQ score, ankle-brachial index (ABI), and treadmill test scores were assessed initially and after 12 weeks.

Results: The WIQ scores were significantly correlated with ABI and pain-free walking distance (PFWD) and maximum walking distance (MWD) in all groups (except for MWD in the intervention group). Speed and stair-climb scores (2 WIQ domains) were well correlated with ABI, PFWD, and MWD. Distance scores were mostly correlated with ABI, PFWD, and MWD in all groups except ABI in the bypass and intervention groups and MWD in the bypass group. Reproducibility was observed in all groups (intraclass correlation coefficient > 0.8).

Conclusion: The Korean version of the WIQ is valid and reproducible, and can be effectively used to assess Korean patients with intermittent claudication.
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http://dx.doi.org/10.4174/astr.2017.93.2.103DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5566744PMC
August 2017

Early Experiences of Sandwich Technique to Preserve Pelvic Circulation during Endovascular Aneurysm Repair.

Vasc Specialist Int 2017 Jun 30;33(2):72-80. Epub 2017 Jun 30.

Department of Surgery, Seoul National University Bundang Hospital, Seongnam, Korea.

Purpose: To report experiences of the sandwich technique (ST) for preservation of pelvic flow during endovascular repair of complex aortic or aortoiliac aneurysms.

Materials And Methods: Eight patients underwent elective endovascular aneurysm repair (EVAR) using the ST between March 2013 and February 2017. The anatomic indications for the ST were complex aortoiliac aneurysms (5 cases), abdominal aortic aneurysms (AAA) with non-diseased short common iliac arteries (2 cases) and AAA with unilateral occluded iliac artery (1 case). The ST was performed through both femoral and brachial approach. Patient clinical and radiologic data were collected and analyzed.

Results: Eight patients (7 male; mean age, 73.4 years) were followed over a mean period of 277 days (range, 9-1,106 days). The technical success rate was 100%. The primary patency rate of the iliac stent-grafts was 88% (14/16 cases). One internal iliac and 1 external iliac stent-graft occlusion was observed during the early postoperative period. There was 1 gutter endoleak which disappeared spontaneously within 4 days, and there were 2 type II endoleaks: one treated by coil embolization after 13 months, and the other observed without treatment. There were no cases of sac growth or aneurysm-related deaths, and no cases of buttock claudication or impotence.

Conclusion: The ST is a safe and feasible technique to preserve pelvic circulation during endovascular treatment of complex aortoiliac aneurysms. The need to expand the indications for complex EVARs with adjunctive procedures, such as the ST is highlighted in situations where branched/fenestrated device availability is limited.
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http://dx.doi.org/10.5758/vsi.2017.33.2.72DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5493190PMC
June 2017

Spontaneous Renal Artery Dissection Complicated by Renal Infarction: Three Case Reports.

Vasc Specialist Int 2016 Dec 31;32(4):195-200. Epub 2016 Dec 31.

Department of Surgery, Seoul National University Bundang Hospital, Seoul National University College of Medicine, Seongnam, Korea.

Spontaneous renal artery dissection (SRAD) is a rare disease entity. The diagnosis is usually delayed because clinical presentation is non-specific. We report three cases of symptomatic SRAD complicated by renal infarction which occurred in previously healthy middle-aged male patients. They visited the hospital due to acute abdominal or flank pain. They had no specific underlying disease or trauma history. The laboratory tests and physical examination were normal. They were not suspected of having SRAD initially, but computed tomography (CT) revealed dissection of the renal artery with distal hypoperfusion leading to renal infarction. They were treated conservatively with anticoagulation and/or antiplatelets for 6 months. They had a 6-month regular follow-up with CT, where resolution was confirmed in one patient and all patients remained asymptomatic. These cases emphasize the importance of clinical suspicion of SRAD in previously healthy patients who complain of abdominal pain without specific findings on initial investigation.
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http://dx.doi.org/10.5758/vsi.2016.32.4.195DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5198768PMC
December 2016

Chronological Change of the Sac after Endovascular Aneurysm Repair.

Vasc Specialist Int 2016 Dec 31;32(4):150-159. Epub 2016 Dec 31.

Department of Surgery, Seoul National University Bundang Hospital, Seongnam.

Purpose: The purpose of this study was to evaluate the potential risk factors of type II endoleak and sac growth after endovascular aneurysm repair (EVAR) and the outcomes of secondary interventions.

Materials And Methods: Ninety seven patients underwent elective EVAR for infrarenal abdominal aortic aneurysms in two tertiary centers between April 2005 and July 2013. Clinical and imaging parameters were compared among sac growth (>5 mm) and non-growth groups. Risk factors associated with sac growth and persistent type II endoleak were analyzed. The outcomes of reinterventions for persistent type II endoleak were determined.

Results: Sac growth was observed in 20 cases (20.6%) and endoleak was found in 90% of them compared to 28.6% (22/77) in the non-growth group (P<0.001). The majority of endoleaks were type II (36/40) and 80.5% were persistent. Sac diameter, neck diameter and number of patent accessory arteries were also statistically significant for sac growth. On multivariate analysis, grade of calcification at the neck, grade of mural thrombus at the inferior mesenteric artery and number of patent accessory arteries were risk factors of persistent type II endoleak. Twenty six reinterventions were done for 16 patients with persistent type II endoleak, with a technical success rate of 88.5%, yet 55.5% showed sac growth regardless of technical success. There were no ruptures during the follow-up period.

Conclusion: Sac growth after EVAR was mostly associated with persistent type II endoleak. Secondary interventions using transarterial embolization is partially effective in achieving clinical success.
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http://dx.doi.org/10.5758/vsi.2016.32.4.150DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5198761PMC
December 2016

Rescue Therapy of Inadvertent Coil Migration for Endovascular Treatment of Type II Endoleak.

Vasc Specialist Int 2016 Mar 31;32(1):22-5. Epub 2016 Mar 31.

Division of Vascular and Transplantation Surgery, Department of Surgery, Seoul National University Bundang Hospital, Seongnam, Korea.

Coil migration during endovascular procedures is not an unusual complication, but there is no standard management strategy for bailout. Here, we describe a technique for removal of a migrated coil using a snare. During embolization of type II endoleak from the inferior mesenteric artery in a post-endovascular aneurysm repair patient, the coil migrated to the sigmoidal artery causing an occlusion. We used a microsnare loop and successfully retrieved the migrated coil. This is the first case in Korea that uses a loop snare for the removal of a migrated coil during visceral endovascular treatment to our knowledge. This technique of using a microsnare for removal of displaced coils can be a good resort in selected cases.
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http://dx.doi.org/10.5758/vsi.2016.32.1.22DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4816022PMC
March 2016

Changes in Saphenous Vein Stump and Low Incidence of Endovenous Heat-Induced Thrombosis After Radiofrequency Ablation of Great Saphenous Vein Incompetence.

Dermatol Surg 2016 Apr;42(4):515-20

*Department of Surgery, Yeouido St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, Korea; †Department of Surgery, Seoul National University Boramae Hospital, Seoul National University College of Medicine, Seoul, Korea; ‡Department of Surgery, Seoul National University Bundang Hospital, Seoul National University College of Medicine, Seoul, Korea.

Background: Relationship between the distance of the catheter tip from the saphenous femoral junction and the length of residual stump after radiofrequency ablation (RFA) has not been sufficiently examined.

Objective: The purpose of this study was to investigate the change of great saphenous vein (GSV) stump with clinical outcomes after RFA.

Material And Methods: From January 2014 to September 2014, 67 patients (91 limbs) underwent GSV RFA and the collected data were analyzed prospectively. Change of GSV stump length and clinical symptoms was evaluated at 1-, 3-, and 6-month intervals. Ablations were performed between 2 to 2.5 cm distal to the saphenofemoral junction.

Results: The residual GSV stump decreased in length to 1.465 ± 0.504 cm at the first month follow-up. This length persisted throughout the 1-, 3-, and 6-month follow-ups. There were no statistically significant differences during the follow-up period. Both the Venous Clinical Severity Score and the Aberdeen Varicose Vein Symptom Severity Score was significantly improved at 1 month and improved even further at 3 months. One patient (1.1%) developed endovenous heat-induced thrombosis (EHIT) Class 3 at 1-month follow-up and was treated with anticoagulation.

Conclusion: This study has shown that the adequate positioning of RFA catheter tip (2.0-2.5 cm) is recommended to decrease the incidence of EHIT.
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http://dx.doi.org/10.1097/DSS.0000000000000674DOI Listing
April 2016

Factors Affecting Length of Hospital Stay and Mortality in Infected Diabetic Foot Ulcers Undergoing Surgical Drainage without Major Amputation.

J Korean Med Sci 2016 Jan 24;31(1):120-4. Epub 2015 Dec 24.

Department of Orthopaedic Surgery, Seoul National University Bundang Hospital, Seongnam, Korea.

This study aimed to investigate factors affecting length of hospital stay and mortality of a specific group of patients with infected diabetic foot ulcer who underwent surgical drainage without major amputation, which is frequently encountered by orthopedic surgeons. Data on length of hospital stay, mortality, demographics, and other medical information were collected for 79 consecutive patients (60 men, 19 women; mean age, 66.1 [SD, 12.3] yr) with infected diabetic foot ulcer who underwent surgical drainage while retaining the heel between October 2003 and May 2013. Multiple linear regression analysis was performed to determine factors affecting length of hospital stay, while multiple Cox regression analysis was conducted to assess factors contributing to mortality. Erythrocyte sedimentation rate (ESR, P=0.034), glycated hemoglobin (HbA1c) level (P=0.021), body mass index (BMI, P=0.001), and major vascular disease (cerebrovascular accident or coronary artery disease, P=0.004) were significant factors affecting length of hospital stay, whereas age (P=0.005) and serum blood urea nitrogen (BUN) level (P=0.024) were significant factors contributing to mortality. In conclusion, as prognostic factors, the length of hospital stay was affected by the severity of inflammation, the recent control of blood glucose level, BMI, and major vascular disease, whereas patient mortality was affected by age and renal function in patients with infected diabetic foot ulcer undergoing surgical drainage and antibiotic treatment.
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http://dx.doi.org/10.3346/jkms.2016.31.1.120DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4712569PMC
January 2016

Role of Laser Doppler for the Evaluation of Pedal Microcirculatory Function in Diabetic Neuropathy Patients.

Microcirculation 2016 Jan;23(1):44-52

Department of Surgery, Seoul National University Bundang Hospital, Seoul National University College of Medicine, Gyeonggi, Korea.

Objective: We evaluated whether LD can detect alterations in skin microcirculatory flow in type II diabetic neuropathy patients and determined which parameters were most predictive.

Methods: A prospective analysis was performed for three groups with presumed varying degrees of microvascular dysfunction: diabetics with neuropathy (DMN, n = 20), diabetics without microangiopathic complications (DM, n = 20), and healthy controls (n = 16). LD was performed under strictly controlled protocols with provocation, consisting of vasoconstrictive (valsalva, postural) and vasodilative tests (PORH, LTH).

Results: There was an overall decrease in LD values in response to both vasoconstrictive and vasodilative provocations in DMN patients compared to DM and control groups. Statistically significant parameters were as follows: valsalva, PORH and LTH between DMN and control; valsalva only between DMN and DM; and PORH and LTH between DM and control. ROC curve analysis showed that Valsalva was the most accurate parameter in DMN patients.

Conclusions: LD could consistently detect differences in microcirculatory flow between the three study groups consisting of gradually more severe microvascular dysfunction. The Valsalva parameter was the most accurate in detecting established microvascular dysfunction, whereas PORH and LTH may have a possible role for detection of early microvascular impairment.
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http://dx.doi.org/10.1111/micc.12254DOI Listing
January 2016

Spontaneous Iliac Vein Rupture.

Vasc Specialist Int 2015 Jun 30;31(2):62-5. Epub 2015 Jun 30.

Department of Surgery, Seoul National University Bundang Hospital, Seongnam, Korea.

Spontaneous iliac vein rupture (SIVR) is a rare entity, which usually occurs without a precipitating factor, but can be a life-threatening emergency often requiring an emergency operation. This is a case report of SIVR in a 62-year-old female who presented to the emergency room with left leg swelling. Workup with contrast-enhanced computed tomography revealed a left leg deep vein thrombosis with May-Thurner syndrome and a hematoma in the pelvic cavity without definite evidence of arterial bleeding. She was managed conservatively without surgical intervention, and also underwent inferior vena cava filter insertion and subsequent anticoagulation therapy for pulmonary thromboembolism. This case shows that SIVR can be successfully managed with close monitoring and conservative management, and anticoagulation may be safely applied despite the patient presenting with venous bleeding.
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http://dx.doi.org/10.5758/vsi.2015.31.2.62DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4508654PMC
June 2015
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