Investigating the safety profiles of exogenous melatonin and associated adverse events: A pharmacovigilance study using WHO-VigiBase.

Melatonin, a pineal hormone that modulates circadian rhythms, sleep, and neurotransmitters, is widely used to treat sleep disorders. However, there are limited studies on the safety of melatonin. Therefore, we aimed to present the overall patterns of adverse events (AEs) following melatonin administration and identify potential safety signals associated with melatonin. Using VigiBase, a global individual case safety report (ICSRs) database managed by the World Health Organization (WHO), we conducted a retrospective, observational, pharmacovigilance study of melatonin between January 1996 and September 2022. Disproportionality analysis was conducted using two comparator settings: all other drugs and other sleep medications. We used multivariable logistic regression to estimate reporting odds ratios (RORs) with 95% confidence intervals (CIs) to compare the frequencies of AEs reporting between melatonin and each comparator setting. Furthermore, we assessed adverse events of special interests (AESIs) that could potentially be associated with melatonin. Signals were identified when the following criteria were met: cases ≥3, x2 ≥ 4, IC025 ≥ 0, and the lower end of the 95% CI of ROR > 2. These signals were then compared with the AE information on the drug labels provided by regulatory bodies. A total of 35 479 AE reports associated with melatonin were identified, with a higher proportion of reports from females (57.1%) and individuals aged 45-64 years (20.8%). We identified 21 AEs that were commonly detected as safety signals in the disproportionality analyses, including tic, educational problems, disturbance in social behavior, body temperature fluctuation, and growth retardation. In AESI analyses, accidents and injuries (adjusted ROR 2.97; 95% CI, 2.80-3.16), fall (2.24; 2.12-2.37), nightmare (4.90; 4.37-5.49), and abnormal dreams (3.68; 3.19-4.25) were detected as a signal of melatonin when compared to all other drugs, whereas those signals were not detected when compared to other sleep medications. In this pharmacovigilance study, exogenous melatonin showed safety profiles comparable to other sleep medications. However, several unexpected potential safety signals were identified, underscoring the need for further investigation at the population level.

Impact of Serum Albumin Levels and Body Mass Index on Outcomes of Open Abdominal Aortic Aneurysm Repair in Korean Population.

BACKGROUND: Although obese patients seem to be susceptible to chronic diseases, obesity paradox has been observed in the field of vascular surgery, in which many previous studies have reported that overweight patients have good postoperative outcomes and underweight patients have poor postoperative outcomes. The purpose of our study is to evaluate the impact of body mass index (BMI) and serum albumin levels, which are evaluated as indicators of nutritional status, on outcomes of open abdominal aortic aneurysm (AAA) repair. METHODS: We reviewed the vascular surgery database of a single tertiary referral center for all patients who underwent open AAA repair due to degenerative etiology from 1996 to 2021. To analyze the effect of BMI, patients were classified into 4 groups according to the Asian-Pacific classification of BMI: underweight (UW) (<18.5 kg/m2), normal weight (NW) (18.5-22.9 kg/m2), overweight (OW) (23-24.9 kg/m2), and obese (OB) (≥25 kg/m2). The χ2, Fisher's exact, and Kruskal-Wallis tests were used to compare demographics, comorbidities, radiologic findings, surgical details, and 1-year mortality rates between the 4 groups. We also compared the preoperative serum albumin levels of each group to assess nutritional status indirectly. Cox's proportional hazards model was performed to determine factors associated with mortality. A Kaplan-Meier survival analysis was performed, and the differences were analyzed by a log-rank test. We did not perform an analysis for 30-day mortality because cases of 30-day mortality in UW patients were rare due to the unbalanced distribution of the number of patients in the 4 groups. RESULTS: Among a total of 678 patients, 22 were classified as UW (3.2%), 200 as NW (29.5%), 183 as OW (27.1%), and 273 as OB (40.1%). The median age was 70 (64-75) years and 577 of 678 (85.1%) patients were male gender. Higher serum albumin level was associated with decreased 1-year mortality (hazard ratio [HR], 0.3; 95% confidence interval [CI], 0.15-0.63; P = 0.001). UW patients had a higher 1-year mortality rate than NW patients (HR, 3.67; 95% CI, 1.02-13.18; P = 0.046). OB patients had a lower overall mortality rate than NW patients (HR, 0.73; 95% CI, 0.53-1; P = 0.05). CONCLUSIONS: Low BMI (<18.5 kg/m2) and low serum albumin level were associated with poor 1-year survival after elective open AAA repair. These patients also need more careful preoperative intervention, like weight gain or nutritional support, for better outcomes. The obesity paradox existed in our study; high BMI (≥25 kg/m2) was associated with better overall survival after elective open AAA repair.

Clinical outcomes and challenges of surgical extirpation for carotid body paraganglioma in South Korea: a single-center retrospective study.

BACKGROUND: Carotid body paraganglioma (CBP) is a rare, highly vascularized, and slow-growing neuroendocrine tumor. Surgical resection is the definitive treatment for CBP, however, it remains challenging due to the tumor's proximity to critical blood vessels and cervical cranial nerves. This study aimed to document the characteristics of CBP and examine the clinical outcomes of patients following surgical extirpation of CBP. METHODS: This is a single-center retrospective review analyzed patients who underwent CBP extirpation. We examined the patient demographics, preoperative clinical features, tumor characteristics, levels of catecholamines and their metabolites in the serum and urine. Surgeries were performed by one vascular surgeon with follow-ups at 1,3,6 months and yearly thereafter. Logistic regression analysis was conducted to identify risk factors associated with the occurrence of either permanent or temporary cervival cranial nerve palsy (CNP). RESULTS: From September 2020 to February 2023, this study examined 21 cases of CBP removal surgeries that were carried out in 19 patients. The mean age of the patients was 38.9 ± 10.9 years and the percentage of males was 57.1% (n = 12). The most common preoperative clinical feature was painless neck mass (n = 12; 57.1%). Complete resection was achieved in 20 cases; excluding one case with pathologically proven sclerosing paraganglioma. Vascular procedures were performed in four cases (ECA resection, n = 2; primary repair of ICA tear without carotid shunting, n = 1; and ICA patch angioplasty with carotid shunting, n = 1). Temporary cranial neurologic complications, specifically aspiration and hoarseness occurred in four (19.0%), and three (14.3%) cases, respectively. Hoarseness associated with permanent CNP persisted for more than 6 months in two cases (9.5%). No recurrence or mortality was observed during the follow-up period. CONCLUSIONS: Surgical resection is the primay treatment approach for CBP; however, it poses risks of vascular or cervical CNP. The intraoperative estimated blood loss was the only identified risk factor for CNP.

The Impact of age and outcomes of high-risk patients on carotid revascularization.

OBJECTIVES: To validate the accuracy of high-risk criteria for carotid endarterectomy (CEA) and analyze the correlation between age and outcome of CEA and carotid artery stenting (CAS) in risk groups. METHODS: We reviewed a prospectively managed vascular surgery database in a single tertiary referral center, and 2482 internal carotid arteries (ICAs) had undergone carotid revascularization from November 1994 to December 2021. To validate high-risk criteria for CEA, patients were classified as high risk (Hr) and normal risk (Nr). Subgroup analysis was performed with patients older or younger than 75 years to investigate the relationship between age and outcome in each group. Primary endpoints were 30-day outcomes including stroke, death, stroke/death, myocardial infraction (MI), and major adverse cardiovascular events (MACEs). RESULTS: A total of 2345 ICAs in 2256 patients were enrolled. The number of patients in the Hr group was 543 (24%) and the number in the Nr group was 1713 (76%). CEA and CAS were performed on 1384 (61%) and 872 (39%) patients, respectively. The 30-day stroke/death rate was higher with CAS than CEA in both the Hr (1.1% vs. 3.9%, p = 0.032) and Nr (1.2% vs. 6.9%, p < 0.001) groups. In unmatched logistic regression analysis of the Nr group (n = 1778), the rate of 30-day stroke/death (OR, 5.575; 95% CI, 2.922-10.636; p < 0.001) was higher for CAS than CEA. In propensity score matching of the Nr group, the rate of 30-day stroke/death (OR, 5.165; 95% CI, 2.391-11.155; p < 0.001) was also higher for CAS than CEA. In the age <75 subgroup of the Hr group (n = 428), CAS was associated with higher 30-day stroke/death (OR, 14.089; 95% CI, 1.314-151.036; p = 0.029). In the age ≥75 subgroup of the Hr (n = 139), there was no difference in 30-day stroke/death between CEA and CAS. In the age <75 subgroup of the Nr group (n = 1318), 30-day stroke/death (OR, 6.300; 95% CI, 2.797-14.193; p < 0.001) was higher in CAS. In the age ≥75 subgroup of the Nr group (n = 460), 30-day stroke/death (OR, 6.468; 95% CI, 1.862-22.471; p = 0.003) was higher in CAS. CONCLUSIONS: In patients older than 75 years in the Hr group, there were relatively poor 30-day treatment outcomes in both CEA and CAS. Alternative treatment is needed that can expect better outcomes in older high-risk patients. In the Nr group, CEA has a significant benefit compared with CAS, and CEA should be recommended more to these patients.

Comparable surgical outcomes of abdominal aortic aneurysm repair in patients with and without Marfan syndrome.

OBJECTIVE: Marfan syndrome (MFS) affects the cardiovascular system. Aortic root aneurysm is a pathognomonic feature of MFS; however, the abdominal aorta is rarely affected. A consensus on surveillance for the abdominal aorta in patients with MFS has not been established. In the present study, we compared the outcomes after open surgical repair (OSR) of abdominal aortic aneurysms (AAAs) in patients with and without MFS. METHODS: We conducted a retrospective, single-center cohort study from 2003 to 2020. We reviewed and compared 28 patients with MFS and 426 patients without MFS who had undergone OSR for AAAs. The baseline characteristics, medical comorbidities, previous cardiovascular surgery, anatomic features of the AAAs, and surgical treatment outcomes were compared between the two groups. RESULTS: The patients with MFS were younger than those without MFS at the AAA diagnosis (47.2 ± 12.3 vs 70.6 ± 7.9 years; P < .001). The proportion of women was also greater for those with MFS (46.4% vs 15.7%; P < .001). The AAAs were most often located at the infrarenal aorta in both groups. However, thoracoabdominal AAAs were more often found among patients with MFS (10.7% vs 0.9%; P < .012). The proportion of symptomatic patients was lower in the MFS group (3.6% vs 21.6%; P = .022). The maximum median diameter of the AAA at surgery was smaller in the patients with MFS (52 mm vs 58 mm; P = .001). However, concomitant aortic dissection (32.1% vs 3.3%; P < .001) was more prevalent among the patients with MFS. Consequent aneurysmal changes in the iliac artery after AAA repair were more frequent in the patients with MFS (7.1% vs 0%; P = .004). No significant differences were found in 30-day or overall mortality between the patients with and without MFS during a median follow-up period of 71 months (interquartile range, 24.7-121.1 months) and 26.7 months (interquartile range, 7.4-69.5 months), respectively. CONCLUSIONS: The surgical outcomes of OSR for AAAs for patients with MFS were not significantly different from those for patients without MFS in a well-established surveillance program of MFS.

White matter hyperintensity determines ischemic stroke severity in symptomatic carotid artery stenosis.

INTRODUCTION: The aim of this study is to investigate the influence of white matter hyperintensity (WMH) on stroke severity and prognosis in patients with symptomatic carotid artery stenosis. METHODS: Patients with symptomatic carotid artery stenosis were retrieved from the Samsung Medical Center stroke registry from January 2011 to December 2016. Stroke severity was categorized into three levels according to National Institutes of Health Stroke Scale (NIHSS): transient ischemic attack (TIA) or transient symptoms with infarction (TSI), mild stroke, and moderate to severe stroke. WMH volume was measured with medical image processing and visualization. The clinical outcome was assessed using the modified Rankin scale on the 90th day from which the latest onset of the neurological symptom. Logistic regression was used to predict stroke severity, and ordinal regression was used to compare the clinical outcome. RESULTS: Among 158 patients, the numbers of patients with TIA or TSI, mild stroke, and moderate to severe stroke were 48 (30.4%), 59 (37.3%), and 51 (32.3%), respectively. The larger WMH volume was associated with moderate to severe strokes (TIA/TSI vs. moderate to severe strokes, odds ratio (OR) 2.318, 95% confidence interval (CI) 1.194-4.502, p = 0.007; mild vs. moderate to severe strokes, OR 1.972, 95% CI 1.118-3.479, p = 0.013). Patients with larger volume of WMH showed poorer clinical outcome (cutoff value: 9.71 cm3, OR 2.099, 95% CI 1.030-4.311, p = 0.042). CONCLUSION: Our study showed that larger WMH volume is associated with more severe stroke and poorer prognosis in patients with symptomatic carotid artery stenosis.

Culture-Negative Mycotic Aortic Aneurysms Probably Have a Less Severe Clinical Nature Than Culture-Positive Counterparts.

BACKGROUND: Mycotic aortic aneurysm constitutes a potentially devastating disease that necessitates prompt suspicion and diagnosis. There is no exact consensus for treatment, but removal of infected tissues and prolonged use of antimicrobials based on the identified causative microorganisms seem widely acceptable and have been similarly practiced worldwide. However, some patients still show no identified microorganisms. In this study, we sought to determine whether there are any clinical significance or differences of note in culture-negative mycotic aortic aneurysms. METHODS: Between October 2003 and August 2018, 71 patients were identified as treated for mycotic aortic aneurysms at a single tertiary institution. Review of medical records and imaging studies were completed to collect the following information: demographics, previous medical/surgical history regarding potential infection sources, laboratory and radiologic findings, clinical presentations, treatment method, and morbidity and mortality rates. For analysis, patients were categorized into two groups: the blood and/or tissue culture-positive (CP) group and the blood and/or tissue culture-negative (CN) group. The latter was further divided as CN with identified microorganism by molecular biologic methods [CN(+)] and CN with no identified microorganism [CN(-)]. RESULTS: More patients in the CP group were symptomatic than were in the CN(+) group (100% vs. 80%; P = 0.034). However, identification of causative microorganisms did not result in a difference in symptom status upon comparing the [CP + CN(+)] and [CN(-)] groups. Inflammatory markers were the most elevated in the CP group and least elevated in the CN(-) group. The aneurysm growth rate seemed slower in the CN(-) group than in the CN(+) and CP groups (1.3 vs. 3.4 vs. 9 mm/month respectively). Aneurysm rupture at initial presentation was more prevalent in the CP group (33.3%). 18F-Fluorodeoxyglucose-positron emission tomography showed increased uptake regardless of whether or not the microorganisms were identified. Early mortality and disease-specific mortality rates during the follow-up period were higher in the CP group but without statistical significance. CONCLUSIONS: Compared with the CP group, the CN groups appeared clinically less severe, and also exhibited a relatively less devastating course as exhibited by the slower aneurysm expansion rate and smaller number of ruptured aneurysms at the initial presentation.

Outcomes after Elective Open Abdominal Aortic Aneurysm Repair in Octogenarians Compared to Younger Patients in Korea.

BACKGROUND: Although the first choice of treatment for abdominal aortic aneurysm (AAA) is endovascular aneurysm repair, especially in elderly patients, some patients require open surgical repair. The purpose of this study was to compare the mortality outcomes of open AAA repair between octogenarians and younger counterparts and to identify the risk factors associated with mortality. METHODS: All consecutive patients who underwent elective open AAA repair due to degenerative etiology at a single tertiary medical center between 1996 and June 2020 were included in this retrospective review. Medical records and imaging studies were reviewed to collect the following information: demographics, comorbid medical conditions, clinical presentations, radiologic findings, surgical details, and morbidity and mortality rates. For analysis, patients were divided into two groups: older and younger than 80 years of age. Multivariate analysis was performed to identify factors associated with mortality after elective open AAA repair. RESULTS: Among a total of 650 patients who underwent elective open AAA repair due to degenerative AAA during the study period, 58 (8.9%) were octogenarians and 595 (91.1%) were non-octogenarians. Patients in the octogenarian group were predominantly female and more likely to have lower body weight and body mass index (BMI), hypertension, chronic kidney disease, and lower preoperative serum hemoglobin and albumin compared with patients in the non-octogenarian group. Maximal aneurysm diameter was larger in octogenarians. During the median follow-up duration of 34.4 months for 650 patients, the median length of total hospital and intensive care unit stay was longer in octogenarians. The 30-day (1.7% vs. 0.7%, P = 0.374) and 1-year (6.9% vs. 2.9%, P = 0.108) mortality rates were not statistically significantly different between the two groups. Multivariate analysis showed that low BMI was associated with increased 30-day (odds ratio [OR], 16.339; 95% confidence interval [CI], 1.192-224.052; P = 0.037) and 1-year (OR, 8.236; CI, 2.301-29.477; P = 0.001) mortality in all patients. CONCLUSION: Because the mortality rate of octogenarians after elective open AAA repair was not significantly different compared with their younger counterparts, being elderly is not a contraindication for open AAA repair. Low BMI might be associated with increased postoperative mortality.

The Effect of Left Renal Vein Division on Renal Function Following Open Abdominal Aortic Surgery Using Propensity Score Matching Analysis.

BACKGROUND: Open surgery of abdominal aortic aneurysm (AAA) or aortoiliac occlusive disease (AIOD) sometimes requires left renal vein division (LRVD) to gain adequate exposure of the abdominal aorta. The aim of this study is to evaluate the effect of LRVD on the postoperative renal function using propensity score matching (PSM). METHODS: From July 1996 to January 2018, we retrospectively reviewed 698 patients who underwent open aortic surgery, including 543 AAAs and 155 AIODs, at a single institution. 66 patients (9.6%, 47 AAAs, 19 AIODs) needed LRVD during the operation. A 1:3 ratio PSM was used to control the selective bias between the LRVD and non-LRVD groups. We investigated preoperative and postoperative renal function including serum creatinine (sCr) level and estimated glomerular filtration rate (eGFR, mL/min/1.73 m2). Major complications, long-term renal function, and 30-day mortality were also compared. RESULTS: The LRVD group had a significantly higher rate of renal artery reconstruction (15.2% vs. 3.3%, P < 0.001) and suprarenal clamping (54.6% vs. 9.5%, P < 0.001) and higher incidence of juxtarenal AIOD (24.2% vs. 5.4%, P < 0.001). With PSM, 63 patients in the LRVD group and 144 patients in the non-LRVD group were enrolled in this study. The baseline characteristics were well balanced in the groups after PSM. There were no significant differences in preoperative eGFR (72.4 ± 21.3 vs. 76.1 ± 25.0, P = 0.306) and postoperative eGFR on day 3 (69.5 ± 26.6 vs. 77.5 ± 28.5, P = 0.065), day 7 (73.3 ± 24.8 vs. 78.5 ± 27.4, P = 0.264), and in the long-term follow-up period (69.0 ± 22.2 vs. 68.9 ± 27.1, P = 0.986, 50.2 month ± 45.50) in the 2 groups. Only the sCr level (1.40 ± 0.59 vs. 1.21 ± 0.62, P = 0.045) and eGFR (59.5 ± 23.9 vs. 71.4 ± 26.0, P = 0.002) were significantly worse on postoperative day 1 in the LRVD than in the non-LRVD group. There were no significant differences in 30-day mortality (1.6% vs. 1.6%, P = 1.00). CONCLUSIONS: The patients in the LVRD group underwent initial drop in renal function; however, eGFR improved during the follow-up period. There was no difference in renal function and postoperative mortality between LRVD and non-LRVD groups. Therefore, LRVD is a safe and durable procedure during complex abdominal aortic surgery.

Comparative Analysis Using Propensity Score Matching Analysis: Primary Closure versus Patch Angioplasty During Carotid Endarterectomy.

BACKGROUND: Primary closure (PC) and patch angioplasty (PA) during carotid endarterectomy (CEA) have been disputed in many studies. Some studies announced that PC is associated with a higher restenosis rate. The aim of this study was to evaluate the outcomes of PC and PA using propensity score matching (PSM). METHODS: Between November 1994 and October 2016, 1,044 patients underwent primary CEA procedures at our institution and were retrospectively analyzed. The study endpoints included rates of ipsilateral stroke, any clinical stroke, cranial nerve palsy, hematoma, bleeding warranting repeat surgery within 30 postoperative days. We also investigated the restenosis rates, overall survival, stenosis-free survival, and stroke-free survival during follow-up (median follow-up 37.1 months). RESULTS: This study includes 435 cases of PC and 476 cases of PA. After PSM analysis, baseline characteristics (age, gender, hypertension, diabetes, dyslipidemia, smoking, atrial fibrillation, previous percutaneous coronary intervention or coronary artery bypass grafting, contralateral carotid occlusion, degree of carotid stenosis, and symptomatic status within 6 months) were balanced. Finally, 377 pairs of matched cases were analyzed. Statistical analysis showed no significant differences between the 2 groups in ipsilateral stroke (P = 0.45), clinical stroke (P = 0.75), cranial nerve palsy (P = 1), hematoma (P = 0.18), bleeding which required reoperation (P = 0.12) within 30 postoperative days, and restenosis rates during follow-up (P = 0.16). In addition, there were no differences between the 2 groups during follow-up in overall, stroke-free, and restenosis-free survival with P values of 0.136, 0.07, and 0.06, respectively. CONCLUSIONS: According to the analysis using PSM, there were no significant differences between PC and PA closure during CEA in perioperative and long-term outcomes.

Endovascular treatment results and risk factors for complications of body and extremity arteriovenous malformations.

OBJECTIVE: The objective of this study was to investigate the factors associated with the complication rate and treatment outcomes of arteriovenous malformations (AVMs) during a 20-year period. METHODS: This was a retrospective study of 306 patients (135 men, 171 women; mean age, 30.8 years) with body and extremity AVMs who were treated between 1996 and 2017. A total of 913 sessions of endovascular treatment were performed. Patients were divided into two decades of the study period to compare complications and clinical results. Group 1 comprised 107 patients treated in the first decade of the study period, and group 2 comprised 199 patients treated in the last decade. AVMs were classified according to the angiographic findings. Complication rates, number of treatment sessions, and treatment results were compared between the two groups. RESULTS: Minor complication (group 1, 20.1%; group 2, 18.5%) and major complication (group 1, 3.1%; group 2, 4.1%) rates were similar between groups (P = .79). The mean number of treatment sessions in group 1 and group 2 was 4.2 and 2.3, respectively, indicating a 45% reduction in treatment sessions (P < .0001). The treatment failure rate decreased from 9.3% in group 1 to 1.5% in group 2 (P = .04). The clinical success rate was 54.2% in group 1 and 64.3% in group 2 (P = .10). CONCLUSIONS: With an accumulation of AVM treatment experience, the number of treatment sessions and the rate of treatment failures were significantly reduced.

Treatment Strategies for Cephalic Arch Stenosis in Patients with Brachiocephalic Arteriovenous Fistula.

BACKGROUND: Cephalic arch is one of the sites most susceptible to stenosis in brachiocephalic arteriovenous fistula (BCAVF). We performed a retrospective study to identify the incidence of cephalic arch stenosis (CAS) in BCAVF, to compare the patency of percutaneous transluminal balloon angioplasty (PTA) with that of cephalic vein transposition (CVT), and to establish the optimal treatment strategy for CAS. METHODS: Between January 2011 and June 2016, 462 patients underwent BCAVF creation. CAS was defined as >50% stenosis at the confluence of the cephalic and axillary veins on ultrasonography. Treatment was planned for clinically significant CAS, which was defined as >25% reduction in flow volume compared to previous examination, elevation of venous pressure, delayed puncture site hemostasis, and/or acute thrombotic occlusion. RESULTS: Seventy-seven (16.7%) patients had CAS and 42 of them (54.5%) were treated for clinically significant CAS. PTA was performed in 36 patients (85.7%), and CVT was done in 6 patients (14.3%) as the initial treatment. Nine patients underwent CVT after PTA, resulting in a total of 15 patients treated with CVT. Investigation of the patency of the 36 cases of PTA and 15 cases of CVT revealed that primary-assisted patency rates at 6 and 12 months were 68.2% and 57.3% for PTA and 100.0% and 87.5% for CVT, respectively (P = 0.038). Secondary patency rates at 6 and 12 months were 72.0% and 56.9% for PTA and 100% and 100% for CVT, respectively (P = 0.010). The median intervention rate was 2.5 interventions per access-year in the 36 cases treated with PTA and 1.5 interventions per access-year in the 15 cases treated with CVT. CONCLUSIONS: CAS is a common cause of BCAVF dysfunction, and careful surveillance is warranted. CVT should be considered for treatment of CAS to achieve better long-term patency with fewer reinterventions.

Natural history of spontaneous isolated celiac artery dissection after conservative treatment.

OBJECTIVE: Optimal treatment of spontaneous isolated celiac artery dissection (SICAD) is not well established because the natural history of this rare disease is poorly understood. We analyzed the natural history of patients who underwent conservative treatment. METHODS: The study included 28 patients with SICAD from December 2008 to January 2017. Our institutional policy of first-line treatment for SICAD patients was conservative, and invasive procedures were reserved for unstable complications such as severe persistent pain, significant organ malperfusion, rapid aneurysmal change, and rupture or concealed rupture. Demographics, clinical features, morphologic characteristics on computed tomography, treatment modalities, and follow-up results of these patients were retrospectively reviewed. RESULTS: Mean age was 52 years, and 89% of patients were male; 86% presented with pain, mostly abdominal, and 14% of cases were detected incidentally on abdominal imaging. None of these patients had unstable complications on admission, and all underwent initial conservative treatment. During the follow-up period (22 ± 20 months), aneurysmal change and propagation of thrombosis were noted in one patient and two patients, respectively, all of whom were managed conservatively without adverse clinical events. No difference in clinical and morphologic outcomes was noted between patients who were treated with antihypertensive therapy and those who were not. Patients with intramural hematoma on initial images showed dynamic vascular remodeling (partial to complete resorption) during the follow-up period compared with patients who had dominant intimal flap on initial images. CONCLUSIONS: The clinical course of patients with SICAD was benign. Even progressive vascular changes during follow-up did not require invasive treatment. Antihypertensive therapy might not modify the clinical course. The short-term results of conservative management are encouraging, but further evaluation with long-term follow-up in a large population is needed.

Treatment strategy based on the natural course for patients with spontaneous isolated superior mesenteric artery dissection.

OBJECTIVE: The optimal treatment of spontaneous isolated superior mesenteric artery dissection (SISMAD) is still not known, and we sought to determine an optimal treatment strategy for patients with SISMAD based on its natural clinical course. METHODS: We retrospectively reviewed consecutive patients with SISMAD treated from 2001 through 2016. Diagnosis and angiographic type of SISMAD were determined with contrast-enhanced computed tomography (CT) scan, and the clinical features were obtained using a fixed form questionnaire. All patients were treated conservatively, except for five who unselectively underwent primary interventional treatment. For the follow-up examinations, clinical features and morphologic changes of superior mesenteric artery dissection were examined with CT angiography every 6 to 12 months. RESULTS: During the past 15 years, 116 patients with SISMAD (male, 92%; mean age, 54.7 ± 10.8 years; symptomatic, 76%) were encountered. Clinical features and morphologic changes on CT examinations were available in 100% and 88% of the patients, respectively, during the mean follow-up of 53 ± 39 months (range, 1-173 months). Of 83 symptomatic patients managed conservatively, 96% achieved pain resolution; 4% experienced prolonged pain, including one patient with bowel gangrene. After pain resolution, 20% of patients developed late recurrence of abdominal pain, which was relieved with conservative management, whereas two patients (12%) required surgery to treat bowel stricture. Follow-up examinations (n = 102) by CT angiography revealed no change in 34%, partial or complete remodeling in 63%, aneurysmal change in 2%, and dissection progression in 1% of the patients. Antithrombotic therapy offered no beneficial effects on either clinical or morphologic outcomes. CONCLUSIONS: With conservative treatment, the majority of patients with SISMAD showed clinical improvement and no morphologic changes during long-term follow-up. We thus recommend a conservative management strategy as the first-line treatment for patients with SISMAD, regardless of angiographic type.

Treatment strategy based on the natural course of the disease for patients with spontaneous isolated abdominal aortic dissection.

OBJECTIVE: This study aimed to determine the natural history of spontaneous isolated abdominal aortic dissection (SIAAD) and to establish an optimal management strategy for patients with SIAAD. METHODS: We searched the database of thoracoabdominal computed tomography (CT) performed at a single institution from January 2003 to July 2016 using the keywords "aortic dissection" and "dissection AND aorta." Once a diagnosis of SIAAD was made, we investigated the initial clinical and morphologic features and aorta-related events for all patients and morphologic changes of the aortic dissection (AD) during the follow-up period for the patients who underwent follow-up CT scans. We compared characteristics of the patients, frequencies of clinical events (aortic rupture, intervention, death), and morphologic changes (false lumen enlargement, progression of AD, remodeling of AD, and involvement of iliac or visceral artery) during the follow-up period according to the location of AD (infrarenal vs suprarenal), symptom status (symptomatic vs asymptomatic), and gender. RESULTS: There were 210 (10.7%) patients (median age, 69.4 years [interquartile range, 61.3-74.7]; male, 73.3%) who were diagnosed with SIAAD among 1958 patients with AD. SIAAD was most frequently located at the infrarenal aorta (86.2%), extended to the iliac (12.4%) or visceral artery (2.9%), and was symptomatic in 13.3% of patients. During the study period, aortic rupture developed in two patients (0.9%), aortic intervention was required in five (2.4%), and aorta-related deaths were identified in three (1.4%). Among 138 (65.7%) patients who underwent follow-up CT scans, 81.9% showed no morphologic change or remodeling during the follow-up period (median, 25 months; range, 1-158 months; interquartile range, 12.3-49.1 months). In the meantime, false lumen enlargement and longitudinal progression of AD developed in 8.7% and 6.5% of patients, respectively. However, newly developed visceral artery extension was not found in any of the patents. When characteristics of the patients and frequencies of clinical events or late morphologic changes of AD were compared on the basis of the location of AD, symptom status, and gender, female gender, presence of symptoms, and suprarenal SIAAD were more frequently associated with aorta-related mortality. False lumen enlargement was more frequent in the suprarenal AD group than in the infrarenal AD group. CONCLUSIONS: Based on our observation, the majority of symptomatic and asymptomatic SIAAD patients can be managed conservatively unless they present with aortic rupture, concomitant large aortic aneurysm, or underlying connective tissue disease. However, a more proactive management strategy may be required for female, symptomatic patients or those with suprarenal SIAAD.

Fibroblast Growth Factor 12 Is a Novel Regulator of Vascular Smooth Muscle Cell Plasticity and Fate.

OBJECTIVE: Vascular smooth muscle cells (VSMCs) modulate their phenotype between synthetic and contractile states in response to environmental changes; this modulation plays a crucial role in the pathogenesis of restenosis and atherosclerosis. Here, we identified fibroblast growth factor 12 (FGF12) as a novel key regulator of the VSMC phenotype switch. APPROACH AND RESULTS: Using murine models and human specimens, we found that FGF12 was highly expressed in contractile VSMCs of normal vessel walls but was downregulated in synthetic VSMCs from injured and atherosclerotic vessels. In human VSMCs, FGF12 expression was inhibited at the transcriptional level by platelet-derived growth factor-BB. Gain- and loss-of-function experiments showed that FGF12 was both necessary and sufficient for inducing and maintaining the quiescent and contractile phenotypes of VSMCs. FGF12 inhibited cell proliferation through the p53 pathway and upregulated the key factors involved in VSMC lineage differentiation, such as myocardin and serum response factor. Such FGF12-induced phenotypic change was mediated by the p38 MAPK (mitogen-activated protein kinase) pathway. Moreover, FGF12 promoted the differentiation of mouse embryonic stem cells and the transdifferentiation of human dermal fibroblasts into SMC-like cells. Furthermore, adenoviral infection of FGF12 substantially decreased neointima hyperplasia in a rat carotid artery injury model. CONCLUSIONS: In general, FGF family members induce a synthetic VSMC phenotype. Interestingly, the present study showed the unanticipated finding that FGF12 belonging to FGF family, strongly induced the quiescent and contractile VSMC phenotypes and directly promoted VSMC lineage differentiation. These novel findings suggested that FGF12 could be a new therapeutic target for treating restenosis and atherosclerosis.

Editor's Choice - Comparison of Early Outcomes and Restenosis Rate Between Carotid Endarterectomy and Carotid Artery Stenting Using Propensity Score Matching Analysis.

OBJECTIVE/BACKGROUND: Despite randomised evidence, the debate continues about the preferred treatment strategy for carotid stenosis in routine clinical practice. The aim of this study was to compare early outcomes and restenosis rates after carotid endarterectomy (CEA) and carotid stenting (CAS) in unselected patients using propensity score matching (PSM). METHODS: The 30 day incidence of major adverse clinical events (MACE; defined as stroke, transient ischaemic attack, myocardial infarction, or death) and procedure related complications, as well as restenosis rates during follow-up were compared between unselected patients undergoing CEA or CAS between January 2002 and December 2015 at a single institution. PSM was used to balance the following factors between the CEA and CAS cohorts: age, sex, hypertension, diabetes, dyslipidaemia, smoking, atrial fibrillation, previous percutaneous coronary intervention or coronary artery bypass grafting, valvular heart disease, contralateral carotid occlusion, degree of carotid stenosis, and symptomatic status. Statistical comparisons of outcomes were based on logistic regression analysis and log rank test. RESULTS: Of 1184 patients (654 CEA and 530 CAS), 452 PSM pairs of CEA and CAS patients were created. The CAS group showed a relatively higher 30 day incidence of MACE (7.5% vs. 2.4%; odds ratio [OR] 3.261, 95% confidence interval [CI] 1.634-6.509; p = .001) but a lower incidence of procedure related complications (1.5% vs. 5.3%; OR 0.199, 95% CI 0.075-0.528; p = .001). During a mean follow-up of 49.1 months (range 1-180 months), restenosis rates were higher after CAS than after CEA (1.5% vs. 1.0% at 12 months and 5.4% vs. 1.2% at 24 months, respectively; p = .008). CONCLUSION: This PSM based observation reconfirmed previous trial results in both asymptomatic and symptomatic patients with carotid artery stenosis in routine clinical practice: CEA showed lower 30 day MACE and mid-term restenosis rates than CAS.

Clinical outcome and predictors of treatment response in foam sodium tetradecyl sulfate sclerotherapy of venous malformations.

OBJECTIVES: To evaluate clinical outcomes and their predictors in patients with venous malformation (VM) treated with foam sodium tetradecyl sulfate (STS) sclerotherapy. METHODS: We retrospectively evaluated clinical outcomes of foam STS sclerotherapy in 86 patients with 91 VMs to assess reduction in pain and mass after treatment. Univariate and multivariate analysis was performed to determine possible predictors of clinical outcome with foam STS sclerotherapy. RESULTS: A positive response of 49.5% in pain reduction and 52.7% in mass reduction was observed. The numerical rating scale (NRS) score improved from 4.36 ± 2.64 to 1.74 ± 1.57, and VM mass volume decreased to 41.7 ± 35.52% of the initial size. On multivariate analysis, a high baseline NRS score (odds ratio: 1.12, 95% confidence interval: 1.09-1.15) and VM location in the trunk versus the head and neck (odds ratio: 1.30, 95% confidence interval: 1.00-1.69) were positive predictors of pain improvement. Minor complications occurred in 11 (12.1%) patients and recurrence in 12 (13.2%) patients. CONCLUSIONS: Foam STS sclerotherapy is an effective treatment in venous malformation, with low complication risk. A high baseline NRS score and location in the trunk versus the head and neck were positive predictors in improvement of pain. KEY POINTS: • Foam STS sclerotherapy is effective in VM, with low risk of complications. • Relief of pain tends to be dramatic in patients with severe pain. • Location of VM is a predictor of pain improvement. • The presence of a draining vein does not affect foam sclerotherapy.

Diagnostic yield of endoscopic ultrasonography-guided single-incision needle knife biopsy for gastric subepithelial tumors: comparison with resected specimens.

BACKGROUND: Several techniques are recommended for the histologic diagnosis of gastric subepithelial tumors (SETs). The purpose of our study was to evaluate the diagnostic yield and safety of endoscopic ultrasonography-guided single-incision needle knife (SINK) biopsy for the diagnosis of gastric SETs. METHODS: A retrospective review of patients who received biopsy for gastric SETs from August 2012 to May 2015 was conducted. Patients who received endoscopic ultrasonography and were found to have a SET originating from the muscularis propria of the stomach were included in the study. The aim of our study was to investigate the safety and diagnostic yield of SINK biopsy for gastric SETs. RESULTS: A total of 31 patients received SINK biopsy for SETs. The diagnostic yield of SINK biopsy was 87 % (95 % CI 75-100 %), and the diagnostic accuracy was 89 % (95 % CI 74-105 %). The sensitivity of SINK biopsy to identify gastrointestinal stromal tumors was 83 % (95 % CI 52-98 %); the specificity was 100 % (95 % CI 59-100 %); the positive predictive value was 100 % (95 % CI 69-100 %); and the negative predictive value was 78 % (95 % CI 40-97 %). There were no procedure-related adverse events during and after procedure. CONCLUSION: The use of SINK biopsy technique in patients with SETs is a good diagnostic tool with high diagnostic yield and accuracy. The method is simple, safe, and associated with few complications.

Comparison of clinical characteristics in patients with Takayasu arteritis with and without concomitant tuberculosis.

Because of frequent tuberculosis in patients with Takayasu arteritis (TA), a possible relationship between TA and tuberculosis has been proposed. However, there are no studies to date that have examined clinical manifestations in patients diagnosed with TA with or without tuberculosis. Two hundred sixty-seven patients were diagnosed with TA according to the 1990 American College of Rheumatology criteria between September 1994 and April 2014. Patients with TA were classified into groups with or without tuberculosis. Among the 267 patients with TA studied, 47 patients (17.7 %) who had a history of previous treatment of tuberculosis (34 patients), concurrent diagnosis of tuberculosis with TA (10 patients), or diagnosis of tuberculosis during the follow-up period for TA (3 patients) were included in the group with tuberculosis. The group with tuberculosis comprised of 33 patients (70.2 %) with pulmonary tuberculosis, 12 patients (25.5 %) with tuberculous lymphadenitis, and 2 patients (4.3 %) with tuberculosis of the skin and colon, respectively. Comorbid disease and patients' signs and symptoms were not significantly different between TA patients with and without tuberculosis. Additionally, the site of disease involvement in angiographic findings and distribution of angiographic type were similar between the two groups. In conclusion, tuberculosis including tuberculous lymphadenitis was frequently observed in patients with TA. Clinical features and angiographic findings in TA were not different according to the presence or absence of concomitant tuberculosis.