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Background and Purpose: The triglyceride-glucose (TyG) index, a novel reliable biomarker for IR that incorporates blood glucose and triglyceride, is linked to intracranial atherosclerotic stenosis (ICAS). In this study, we aimed to further investigate the association between the TyG index and the outcomes of ICAS patients following extracranial-to-intracranial (EC-IC) bypass grafting., Methods: 489 ICAS patients who underwent EC-IC bypass between Jan 2009 and Jan 2022 at our hospital were retrospectively collected. The major adverse cardiac and cerebrovascular events (MACCEs), and anastomotic restenosis, both of which are critical factors leading to poor prognosis of ICAS patients after EC-IC bypass, were mainly recorded and analyzed. Kaplan-Meier survival curve and Log-rank tests were sequentially conducted. Cox regression model was used to investigate the association between the TyG index and MACCEs & anastomotic stenosis. C-statistics, continuous net reclassification improvement (NRI), and integrated discrimination improvement (IDI) evaluated the incremental predictive value of the TyG index., Results: A higher incidence of MACCEs and anastomotic stenosis was found in higher-tertile TyG index group. The TyG index was significantly associated with an increased risk of MACCEs and anastomotic stenosis, independent of confounding factors, with a value of HR (1.30, 95%CI 1.10-1.51, p  < 0.001) and (1.27, 95%CI 1.16-1.40, p  < 0.001) respectively. The area under the curve (AUC) in the model with the TyG index for predicting the occurrence of MACCEs and anastomotic stenosis were 0.708 (95%CI 0.665-0.748) and 0.731 (95%CI 0.689-0.770) respectively. The addition of the TyG index significantly improved the global performance of the baseline model according to the C-statistics, NRI, and IDI (All p  < 0.05)., Conclusions: Higher TyG levels were associated with poorer outcomes in ICAS patients after EC-IC bypass. TyG could be a key factor in managing ICAS risk and standardizing the indications for EC-IC bypass.

Objective: Expanding on previous investigations, this study aims to elucidate the role of lipid metabolism disorders in the development of intracranial atherosclerotic stenosis (ICAS) and the determination of stroke risk. The primary objective is to explore the connections between lipid parameters and acute ischemic stroke (AIS), while also examining the potential mediating influence of fasting glucose levels., Methods: Retrospectively, we collected data from symptomatic ICAS patients at the First Affiliated Hospital of Soochow University, including their baseline information such as medical histories and admission blood biochemical parameters. Stenotic conditions were evaluated using magnetic resonance imaging, computed tomography angiography, or digital subtraction angiography. The associations between lipid parameters and AIS risks were investigated via multivariate logistic regression analysis., Results: A total of 1103 patients with symptomatic ICAS were recruited, among whom 441 (40.0%) suffered new ischemic events during hospitalization. After adjusting for confounding factors, the RCS curves exhibited a dose-response relationship between the atherogenic index of plasma (AIP), total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), and AIS. Further multivariate analysis revealed significant associations between these parameters and AIS. Furthermore, mediation analysis indicated that fasting blood glucose (FBG) acted as a mediator in the association between lipid parameters (AIP, TC, and TG) and AIS., Conclusion: Higher lipid parameters in ICAS patients, particularly AIP, TC, and TG, were associated with an increased AIS risk. Additionally, FBG may mediate stroke risk in ICAS patients, highlighting the need for further exploration of underlying mechanisms., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Li, Wang, Zhu, Zheng, Ni, Li and Yang.)

The Shiga Epidemiological Study of Subclinical Atherosclerosis was conducted in Kusatsu City, Shiga, Japan, from 2006 to 2008. Participants were measured for LDL-p through nuclear magnetic resonance technology. 740 men participated in follow-up and underwent 1.5 T brain magnetic resonance angiography from 2012 to 2015. Participants were categorized as no-ICAS, and ICAS consisted of mild-ICAS (1 to < 50%) and severe-ICAS (≥ 50%) in any of the arteries examined. After exclusion criteria, 711 men left for analysis, we used multiple logistic regression to examine the association between lipid profiles and ICAS prevalence. Among the study participants, 205 individuals (28.8%) had ICAS, while 144 individuals (20.3%) demonstrated discordance between LDL-c and LDL-p levels. The discordance "low LDL-c-high LDL-p" group had the highest ICAS risk with an adjusted OR (95% CI) of 2.78 (1.55-5.00) in the reference of the concordance "low LDL-c-low LDL-p" group. This was followed by the concordance "high LDL-c-high LDL-p" group of 2.56 (1.69-3.85) and the discordance "high LDL-c-low LDL-p" group of 2.40 (1.29-4.46). These findings suggest that evaluating LDL-p levels alongside LDL-c may aid in identifying adults at a higher risk for ICAS., (© 2024. The Author(s).)

Background: Ischemic type biliary lesions (ITBLs), a particular subset of non-anastomotic biliary strictures (NAS), are characterized by intra and extrahepatic strictures that occur in the absence of either hepatic artery thrombosis or stenosis. When they occur within the first year after liver transplantation their development is mostly related to ischemia-reperfusion injury (IRI). The indocyanine green plasma disappearance rate (ICG-PDR) might be able to predict the probability of IRI-induced graft damage after liver transplantation., Objective: Our aim was to evaluate the association between ICG-PDR and the occurrence of ITBLs. Secondly, we searched for evidence of IRI in patients presenting ITBLs., Methods: This retrospective single-center observational study assessed a cohort of 60 liver transplant patients. Each patient underwent ICG-PDR on the 1st postoperative day. ITBLs were identified by means of either cholangiography or magnetic resonance imaging evidence of a deformity and narrowing of the biliary tree in the absence of hepatic artery thrombosis/stenosis., Results: ITBLs were discovered in 10 patients out of 60 liver recipients (16.67%) within one year after transplantation. A low ICG-PDR value was found to be a significant predictive factor for ITBL development, with an OR of 0.87 and a 95% CI of 0.77-0.97. Liver biopsies were performed in 56 patients presenting unexplained abnormal liver function test results. A statistically significant association was found between the development of ITBLs and anatomopathological evidence of IRI., Limitations: Retrospective, single-center study., Conclusions: The findings from this study show a relationship between low ICG-PDR values on first post-operative-day and the occurrence of ITBLs within 1 year after transplantation., (Copyright © 2021 Elsevier España, S.L.U. All rights reserved.)

Aims: Diabetes mellitus (DM) is one of the main risk factors for intracranial cerebral artery stenosis (ICAS), and fasting blood glucose (FBG) might be an effective predictor of ICAS. However, there are a few studies revealing the relationship between FBG and ICAS. We aim to identify the association between FBG and ICAS in Koreans., Methods: This was a secondary study based on a cross-sectional study. A total of 1011 Korean individuals who were asymptomatic but with high cerebrovascular risk underwent an examination in a Korean medical centre from March 2008 to December 2014. The main measure was FBG, while the main outcome was ICAS. Multivariate logistic regression analyses of FBG in the presence of ICAS were performed to examine the potential association. The author used the data provided by the paper "Association between Serum Alkaline Phosphatase Level and Cerebral Small Vessel Disease" for secondary analysis., Results: The average age of the participants was 64.2 ± 9.1 years old, and approximately 35% of them were males. There were 24 participants suffering from ICAS in the first FBG tertile (< 5.4 mmol/L), while there were 26 in the second tertile (5.4-7.1 mmol/L) and 50 in the third tertile (≥ 7.1 mmol/L). The non-adjusted relationship between FBG and ICAS was positive. After controlling potential confounders, the association of FPG with ICAS remained positive, as well as in subgroups analysis, such as age, sex, hypertension, diabetes mellitus, hyperlipidaemia and COAD. The association remained unchanged after adjusted sex, age, hypertension, DM, uric acid, hyperlipidaemia, and CAOD (OR = 1.08, 95% CI = 1.02-1.15). The analyses also showed that the positive association was statistically significant (P < 0.05) among individuals without diabetes., Conclusions: This study showed a positive relationship between FBG and ICAS, which suggests that clinicians may need to be simultaneously concerned about FBG and ICAS.

Background: In primary care, there is a need for simple and cost-effective tool that will allow the determination of the risk of coronary artery disease (CAD). We aimed to research the value of glycosylated hemoglobin (HbA1c) in the prediction of coronary artery disease., Methods: Patients admitted to the outpatient clinic of the Cardiology for angiography were retrospectively screened. Patients with diabetes or with HbA1c of 6.5 or above were excluded. Comparative HbA1c data were obtained according to the stenosis groups. Logistic regression analysis was used to investigate the risk factors affecting stenosis positivity., Results: Of the study group, 120 patients were without any stenosis in any coronary artery, 56 patients were with >50% stenosis in one coronary artery, and 71 patients were with >50% stenosis in more than one coronary artery. There was a statistically significant difference between HbA1c measurements according to the degree of stenosis (P = .001 and P < .01, respectively). The odd ratio for HbA1c was 6.260 (95% CI: 3,160-12,401). According to the stenosis positivity, the cutoff point for HbA1c was found to be 5.6 and above. In the regression analysis, HbA1c was an independent risk factor for CAD. One unit increase in HbA1c level increases the risk of stenosis up to 12.4-fold (95% CI: 5,990-25,767)., Conclusion: The study showed HbA1c can be used as an independent marker in determining the probability and severity of coronary artery disease in non-diabetic individuals and as a useful marker in primary care predicting CAD., (© 2020 The Authors. Journal of Clinical Laboratory Analysis Published by Wiley Periodicals LLC.)

In-stent restenosis (ISR) is one of the main complications in patients undergoing percutaneous coronary angioplasty, and microRNAs participate in the contractile-to-synthetic phenotypic switch of vascular smooth muscle cells, a hallmark of restenosis development. MicroRNAs (miRNAs) can be released into circulation from injured tissues, enticing a potential role as noninvasive biomarkers. We aimed to evaluate circulating levels of miRNA-23b, miRNA-143, and miRNA-145 as diagnostic markers of ISR. 142 patients with coronary artery disease undergoing successful angioplasty and a follow-up angiography were included. Subjects were classified according to the degree of obstruction at the angioplasty site into cases (≥50%) or controls (<50%). Total RNA was isolated from plasma to quantify circulating miRNAs levels, and the ROC curves were constructed. Among circulating miRNAs assessed, miRNA-23b and miRNA-143 were significantly lower in cases (miRNA-23b: 18.4x10 -5 and miRNA-143: 13.7x10 -5 ) than controls (miRNA-23b: 5.2x10 -5 , p < 0.0001; miRNA-143: 4.0x10 -5 , p < 0.0001). Plasma levels of miRNA-145 showed no significant differences. The analysis of the ROC curves showed an area under the curve for miRNA-23b of 0.71 (95% CI: 0.62-0.80, p < 0.0001) and 0.69 for miRNA-143 (95% CI: 0.60-0.78; p < 0.0001). Our data suggest that plasma levels of miRNA-23b and miRNA-143 could be useful as noninvasive biomarkers of ISR., Competing Interests: The authors declare no conflict of interest., (Copyright © 2020 Nicolás Saavedra et al.)

Intestinal fibrosis and subsequent stricture formation are major clinical challenges in inflammatory bowel disease, resulting in an increased rate of operation and poor prognosis compared with those without. With the changing perception that intestinal fibrosis is irreversible to the point of view that it is reversible in recent years, various candidate serum biomarkers have been studied over the past decades, which may stratify patients based on their risks of developing stenosis and enable the detection of early stages of fibrosis. However, reliable and accurate biomarkers are still unavailable due to conflicting results and the lack of high-quality evidence. In this review we summarized the serum biomarkers that have been proposed for intestinal fibrosis in recent years, which includes gene polymorphisms or variants, epigenetic markers, extracellular matrix components, growth factors, and antibodies, aiming to provide clues for future research., (© 2020 Chinese Medical Association Shanghai Branch, Chinese Society of Gastroenterology, Renji Hospital Affiliated to Shanghai Jiaotong University School of Medicine and John Wiley & Sons Australia, Ltd.)

Background: Although individual lipid parameters have been frequently examined in association with asymptomatic intracranial arterial stenosis (aICAS), few population-based studies have investigated the lipid profiles associated with aICAS among Chinese adults., Objective: This study aims to characterize the lipid profiles associated with aICAS in rural-dwelling adults in China., Methods: This population-based study included 2027 persons who were aged ≥40 years and free of stroke. Data were collected via interviews, clinical examinations, and laboratory testing. We diagnosed aICAS by integrating transcranial color Doppler with magnetic resonance angiography. Data were analyzed using binary and multinomial logistic regression models., Results: Of the 2027 participants, 154 were detected with aICAS. The multiadjusted odds ratio (95% confidence interval) of aICAS was 1.41 (0.997-2.00) for high small dense low-density lipoprotein cholesterol, 1.44 (1.02-2.04) for high lipoprotein(a), 1.71 (1.21-2.44) for low apolipoprotein A-1, 1.43 (1.00-2.04) for low high-density lipoprotein cholesterol (HDL-C), 1.61 (1.14-2.27) for high apolipoprotein B/apolipoprotein A-1 ratio, 1.95 (1.38-2.76) for high low-density lipoprotein cholesterol/HDL-C ratio, and 1.51 (1.06-2.14) for high total cholesterol/HDL-C ratio. When severity of aICAS was analyzed, high levels of lipoprotein(a), small dense low-density lipoprotein cholesterol, and lipid ratios were significantly associated with an increased likelihood of moderate-to-severe aICAS (P < .05). An increasing number of abnormal lipid measurements was associated with an increased likelihood of aICAS (P for trend <.001)., Conclusion: These findings suggest that lipid profiles for aICAS among rural residents in China are characterized by high atherogenic cholesterol, low antiatherogenic cholesterol, and high ratios of atherogenic-to-antiatherogenic cholesterol or lipoproteins., (Copyright © 2020 National Lipid Association. Published by Elsevier Inc. All rights reserved.)

Background: Antimicrobial peptide expression is associated with disease activity in inflammatory bowel disease (IBD) patients. IBD patients have abnormal expression of elafin, a human elastase-specific protease inhibitor and antimicrobial peptide. We determined elafin expression in blood, intestine, and mesenteric fat of IBD and non-IBD patients., Methods: Serum samples from normal and IBD patients were collected from two UCLA cohorts. Surgical resection samples of human colonic and mesenteric fat tissues from IBD and non-IBD (colon cancer) patients were collected from Cedars-Sinai Medical Center., Results: High serum elafin levels were associated with a significantly elevated risk of intestinal stricture in Crohn's disease (CD) patients. Microsoft Azure Machine learning algorithm using serum elafin levels and clinical data identified stricturing CD patients with high accuracy. Serum elafin levels had weak positive correlations with clinical disease activity (Partial Mayo Score and Harvey Bradshaw Index), but not endoscopic disease activity (Mayo Endoscopic Subscore and Simple Endoscopic Index for CD) in IBD patients. Ulcerative colitis (UC) patients had high serum elafin levels. Colonic elafin mRNA and protein expression were not associated with clinical disease activity and histological injury in IBD patients, but stricturing CD patients had lower colonic elafin expression than non-stricturing CD patients. Mesenteric fat in stricturing CD patients had significantly increased elafin mRNA and protein expression, which may contribute to high circulating elafin levels. Human mesenteric fat adipocytes secrete elafin protein., Conclusions: High circulating elafin levels are associated with the presence of stricture in CD patients. Serum elafin levels may help identify intestinal strictures in CD patients., Competing Interests: The authors have declared that no competing interests exist.

Background: The success rate for the production of animal models of chronic postischemia pain (CPIP) using an O-ring has yet to be improved in the study of complex regional pain syndrome-type I (CRPS-I), and producing a CPIP model is challenging, especially for mice., Objectives: We devised a new CPIP model with a higher success rate that induces ischemia for 3 hours by tying the hind limbs of mice with a rubber band, followed by reperfusion., Study Design: A randomized, controlled animal trial., Methods: Twenty-two male C57BL/6 mice were divided into a sham (n = 6), a ring (n = 8), and a tie group (n = 8). Anesthesia was induced using isoflurane. A precut O-ring was mounted on the upper left ankle in the sham group. A tight-fitting O-ring and a push-pull gauge manometer were mounted at the same location in the ring and tie groups, respectively. Reperfusion was induced 3 hours later. The thickness and circumference of the hind paws were measured before ischemia induction. Measurements were repeated 10 days after reperfusion. Mechanical allodynia was measured with a von Frey filament until 12 weeks after reperfusion., Results: The new tie model required 5 additional days until the onset of allodynia compared with the existing CPIP O-ring model. However, the successful induction rate of CPIP was higher in the tie group than in the ring group, and allodynia was maintained for over 30 days in the tie group. The ring and tie groups exhibited significantly high levels of tumor necrosis factor-alpha than those in the sham group., Limitations: First, we did not evaluate hyperalgesia, cold or heat allodynia. Second, we did not measure blood levels of inflammatory or antiinflammatory cytokines, and research on oxidative stress biomarkers such as isoprostane, 8-hydroxy-2'-deoxyguanosine (a marker of DNA oxidative damage), and malondialdehyde was not performed., Conclusions: The new CPIP tie model has a higher rate of successful induction than existing O-ring models for mice, with longer duration of mechanical allodynia. The model may reduce the number of animals sacrificed in CRPS-I research and could be useful for studying long-term effects of drugs., Key Words: CPIP, mouse, O-ring, rubber band, reperfusion, allodynia, hyperalgesia.

Background: The aim of the present study was to establish an animal model of Yang-Monti ileal ureter-bladder anastomosis and Yang-Monti ileal ureter-ureteral anastomosis and compare the advantages and disadvantages of the two surgical methods., Methods: Fourteen 12-month-old male Chinese miniature pigs weighing 21 ± 1.38 kg were randomly divided into two groups. Group A (n = 7) underwent end-to-end anastomosis of the left Yang-Monti ileal ureter, left ileal ureter and left lower ureter; group B (n = 7) underwent anastomosis of the left Yang-Monti ileal ureter, left ileal ureter and bladder. In both groups, the contralateral kidney was removed at 1 week postoperatively. The incision length and operation time of the two groups were compared. Changes in serum creatinine and urea nitrogen were observed preoperatively, and at 2, 6 and 12 weeks postoperatively. Venous pyelography and cystography were performed at 12 weeks postoperatively to determine the ureteral patency and vesicoureteral reflux. At 12 months postoperatively, urinary culture was performed, and the diameter and histological changes of the intestinal ureter were assessed., Results: Surgery was successfully completed in all 14 pigs. In group A, one pig died due to an anesthetic accident, and one pig died from a lung infection on postoperative day 4. In group B, one pig died from adhesive intestinal obstruction on postoperative day 7. The overall survival rate was 78.6%, and the 11 surviving pigs had no urinary or intestinal fistulae. Compared with group B, group A had a significantly longer surgical incision (30.86 ± 2.41 cm versus 26.71 ± 3.64 cm; p = 0.01) and shorter operation time (181.29 ± 15.10 min versus 157.71 ± 20.49 min; p = 0.02). The serum creatinine and urea nitrogen concentrations did not significantly differ between groups. All pigs had normal renal function pre- and postoperatively. There was no stenosis or obstruction on venous pyelography. The narrowest diameter of the ureter was significantly smaller in group B (5.90 ± 0.30 mm) than in group A (7.26 ± 1.06 mm; p = 0.01), but no contrast agent returned to the upper urinary tract in either group. Escherichia coli was detected on urine culture. In group A, one pig had obstruction of the ureteral ureter, while another had stenosis of the lower ureteral anastomosis. In group B, one pig had pelvic and intestinal ureteral dilatation; however, all anastomoses were patent. The ileal ureteral diameter was significantly larger in group A (9.40 ± 2.35 mm) than group B (6.62 ± 0.37 mm; p = 0.02). Two pigs in group A had separation of the transitional epithelium and columnar epithelial mucosa, with granulation tissue hyperplasia. The pigs with stenosis and obstruction had smooth fibrous tissue and smooth muscle of the anastomosis. In both groups, the two types of epithelial tissue were close together, and the intestinal villi were mildly atrophied and shortened., Conclusions: An animal model of Yang-Monti ileal ureter-bladder anastomosis was successfully established. Compared with Yang-Monti ileal ureter-ureteral anastomosis, Yang-Monti ileal ureter-bladder anastomosis is simpler, more reliable, and results in fewer complications.

Multiterritorial atherosclerosis has dramatically increased annual risk of adverse cardiovascular events than atherosclerotic disease with single-artery affected. Serum uric acid (SUA) is an important predictor of stroke and atherosclerosis; however, which is supported by few direct evidence based on cohort studies. A prospective cohort study including 2644 North Chinese adults aged ≥40 years was performed in 2010-2012 to investigate the association between SUA and multiterritorial vascular stenosis. Hyperuricaemia was defined as SUA levels >6 and >7 mg/dL for males and females, respectively. All participants underwent twice transcranial Doppler (TCD) and bilateral carotid duplex ultrasound to evaluate intracranial artery stenosis (ICAS) and extracranial arterial stenosis (ECAS) and peripheral arterial disease (PAD) was determined by ankle-brachial index (ABI) on January 2010 and January 2012 based on regular health check-ups. The cumulative incidence of vascular stenosis was significantly higher in subjects with hyperuricaemia than in those without hyperuricaemia (54.1% vs. 34.7%, P < 0.001). The adjusted odds ratios (ORs) with 95% confidence intervals (CIs) for new on-set vascular stenosis due to hyperuricaemia and a 1-mg/dL change in SUA level were 1.75 (1.32-2.31) and 1.29 (1.21-1.38), respectively. Furthermore, in the gender-stratified analysis, the association between SUA levels and ICAS was statistically significant in males (OR: 2.02; 95% CI: 1.18-3.46), but not females (OR: 0.85, 95% CI: 0.41-1.76, P for interaction: 0.026)., (© 2019 The Authors. Journal of Cellular and Molecular Medicine published by John Wiley & Sons Ltd and Foundation for Cellular and Molecular Medicine.)

Background: The aim of this study was to identify predictive criteria of improvement after endoscopic treatment (ET) for severe strictures of extrahepatic bile ducts in patients with primary sclerosing cholangitis (PSC)., Methods: PSC patients who had at least one ET for severe stricture were included. Features of magnetic resonance cholangiography (MRC), performed before ET, were evaluated according to a standard model of interpretation, and a radiologic qualitative score of probability of improvement after ET was built. Score 3 (likely) was given in case of severe common bile duct (CBD) stricture with marked dilatation without severe strictures of upstream ducts, Score 1 (unlikely) was given in case of severe multiple strictures of secondary ducts without biliary dilatation and Score 2 (undeterminate) was given to an intermediate pattern. The response to ET was assessed at 2 months (T2-response) from the last ET and at 12 months (T12-response) from inclusion., Results: Thirty-one patients were included. All had severe stricture (reduction ≥ 75% of the diameter) of CBD and 50% had severe stricture of right and/or left hepatic duct (LHD) at MRC before ET. According to the qualitative score, 16 patients had Score 3, 7 had Score 1 and 9 had Score 2. T12-response was obtained in 50% of patients. In univariate analysis, short LHD strictures, bilirubin, transaminases, pruritus and Score 3 were associated with T12-response. Increased bilirubin and transaminases were independent predictive factors of T12-response (HR 24, 95% CI: 3.4-170.4, P = 0.001 and 23.8, 95% CI: 3.4-169.4, P = 0.002, respectively)., Conclusion: MRC, together with biochemical features, may contribute to identify the PSC patients who are likely to be improved after ET for severe strictures of extrahepatic bile ducts., (Copyright © 2019 Elsevier Masson SAS. All rights reserved.)

We determined the relevance between the TG-to-HDL-C ratio and stent restenosis. Ninety-nine patients with in-stent stenosis (ISR) who were admitted to An Zhen Hospital in Beijing between April 2014 and June 2017 were selected. At the same time, 122 patients with coronary stenosis <50% were selected. All patients were tested for TG, HDL-C, and TG/HDL-C ratio. Optical coherence tomography (OCT) can assess microscopic status in all ISR patients. The proportion of male and Diabetic patients were significantly higher for ISR. There were differences in the prevalence of cigarette smokers among the different tissue types, among which the layered tissue type accounted for the highest proportion. In logistic regression analysis the study showed that male, diabetes mellitus, and the TG/HDL-C ratio are risk factors for ISR. The ISR ROC was 0.725 based on the TG/HDL-C ratio diagnosis. It is related to the degree of coronary stenosis and effective in diagnosing in-stent stenosis in ISR.

Objectives: To evaluate CT findings of biliary strictures in ABO-incompatible living donor liver transplantation (LDLT) recipients, with emphasis on associated 1-month post-transplantation CT findings, and evaluate clinical outcomes., Methods: Of 351 ABO-incompatible recipients, we retrospectively evaluated CT scans in 65 recipients with biliary stricture. The biliary strictures on CT scans were classified as type A (perihilar) and type B (diffuse). Precedent CT abnormality patterns and the presence of a periportal halo sign at 1-month post-transplantation were evaluated. For each patient, clinical outcomes were evaluated., Results: Of 65 ABO-incompatible recipients with biliary strictures, 36.9% had type B strictures. Compared with biliary strictures at diagnosis, similar CT abnormality patterns were observed for 84.4% in type A and 86.4% in type B strictures at 1-month post-transplantation. Complex periportal halo signs on the 1-month post-transplantation CT were more frequently noted for type B than type A strictures (86.4% vs. 3.1%, P < 0.001). Progressive clinical outcomes were more frequently observed for type B than type A strictures (79.2% vs. 26.8%, P < 0.001), with a significantly shorter graft survival time (46.4 months vs. 90.8 months, P < 0.001)., Conclusion: CT abnormality patterns and complex periportal halo signs on 1-month post-transplantation CT may be clinically useful for managing biliary strictures in ABO-incompatible LDLT recipients. Key Points • Of ABO-incompatible LDLT recipients, type B biliary stricture incidence was 6.8%. • Of type B strictures, 86.4% exhibited similar CT abnormality patterns at 1-month post-transplantation. • Complex periportal halo at 1 month was significantly associated with type B strictures. • Progressive clinical outcomes were more frequently observed in type B strictures.

Cerebral artery stenosis (CAS) is the most important causes of ischaemic stroke. Lipoprotein-associated phospholipase A2 (Lp-PLA2) plays 2 diverse roles in atherosclerosis (pro-inflammatory and anti-inflammatory), and the association between Lp-PLA2 mass and cardiovascular or cerebrovascular events is inconsistent among previous studies. A cross-sectional study including 2012 North Chinese adults aged ≥40 years was performed in 2010-2011 to investigate whether Lp-PLA2 mass is associated with asymptomatic cerebral artery stenosis (ACAS). Serum Lp-PLA2 mass was determined by enzyme-linked immunosorbent assay (ELISA). All participants underwent transcranial Doppler (TCD) and bilateral carotid duplex ultrasound to evaluate intracranial artery stenosis (ICAS) and extracranial arterial stenosis (ECAS). The median serum Lp-PLA2 mass of the participants was 140.74 ng/mL (interquartile range: 131.79-158.07 ng/mL). The adjusted odds ratio (OR) when comparing the 4th quartile to the 1st quartile of Lp-PLA2 was 1.98 (95% confidence interval (CI): 1.42-2.78), 1.79 (95% CI: 1.08-2.94) and 1.87 (95% CI: 1.28-2.73) for the occurrence of ACAS, asymptomatic ECAS and asymptomatic ICAS, respectively, after controlling for vascular risk factors. These independently significant associations remained statistically significant in the male or elderly subgroups, but not in females or middle-aged participants. Lp-PLA2 mass is positively correlated with subclinical atherosclerosis determined by ACAS, ICAS and ECAS in North Chinese, particularly in male and older participants, suggesting that serum Lp-PLA2 mass might be potential biomarker for the detection of ACAS in the adults., (© 2018 The Authors. Journal of Cellular and Molecular Medicine published by John Wiley & Sons Ltd and Foundation for Cellular and Molecular Medicine.)

Donor-specific alloantibodies (DSA) have been associated with rejection and shorter graft survival after orthotopic liver transplantation (OLT). We examined the role of DSA in nonanastomotic biliary strictures (NAS) after OLT. Patients receiving first OLT who developed NAS (n = 68) and a control group without NAS (n = 83), with pre-OLT and 12 months post-OLT serum samples, were included. DSA were specified using the Luminex single antigen test. Risk factors for NAS and graft survival were analyzed. The presence of preformed DSA was not significantly different between patients with NAS and controls (P = .89). After 12 months, 26.5% of NAS patients and 16.9% of controls had generated de novo DSA (P = .15). Neither de novo class I DSA nor de novo class II DSA were associated with NAS. De novo DSA generally developed after the diagnosis of NAS. Time-dependent regression analysis identified both NAS (aHR 8.05, CI 3.28 - 19.77, P < .01) and de novo class II DSA (aHR 2.84, CI 1.38 - 5.82, P < .01) as independent risk factors for graft loss. Preformed or de novo DSA were not associated with the development of NAS. However, NAS as well as de novo class II DSA were independent risk factors for graft loss after OLT., (© 2017 The Authors. Clinical Transplantation Published by John Wiley & Sons Ltd.)

Accumulation of cholesterol and other atherogenic lipids such as low-density lipoprotein (LDL) in artery wall causes reduction of vessel diameter and artery stenosis. The study of the mass transfer of these large molecules in the wall with considering effective factors on lumen flow and different physiological factors is the subject considered nowadays. In this paper, results of two dimensional and axi-symmetric simulations of three different models of the artery with 60% stenosis under pulsatile blood flow are presented. Filtration velocity of LDL mass transport in the permeable artery wall and shear stress of blood flow are investigated using ADINA software Three different flow models are considered. In the first and second models, the filtration velocity considered as a given parameter and constant in arterial wall boundary, while in third model arterial wall considered as porous wall, the filtration velocity is calculated from pressure difference as an input parameter of the model. The results show that filtration velocity is strongly depend on geometry and it is not constant along the wall, contrary to simplified models. The results of concentration variations in lumen and wall illustrate the increase in near wall LDL concentration or concentration polarization.

Background/aims: Acute ischemic stroke is caused by stenosis of artery supplying to brain. We aimed to detect some metabolites in the serum that would be related to the degree of artery stenosis and to analyze potential mechanisms., Methods: Patients diagnosed with acute ischemic stroke were divided into two groups according to their degree of artery stenosis (which was determined by computed tomographic angiography): a mild group (stenosis ≤ 30%) and a severe group (stenosis > 30%). Serum from these patients was collected, and we focused on the differences in the concentrations of calcium, uric acid, low density lipoprotein and homocysteine. The dataset GSE11583 from the Gene Expression Omnibus database was analyzed to find the potential mechanism using bioinformatics methods., Results: Among the four metabolites, the only difference that reached significance between the two groups was in the concentration of calcium in serum (2.27±0.08 mmol/L vs 2.21±0.08 mmol/L). By comparing the gene expression levels between normal endothelial cells and adaptive remodeling endothelial cells in GSE11583, we identified 51 upregulated and 40 downregulated genes in adaptive remodeling endothelial cells. The gene set enrichment analysis revealed that upregulated genes were enriched in a phosphatidylinositol signaling system, which is closely involved in the calcium signaling pathway., Conclusion: Our results suggest that the concentration of serum calcium is higher in patients with more severe artery stenosis lesions and that the phosphatidylinositol signaling system is a key biological pathway involved in this process., (© 2018 The Author(s). Published by S. Karger AG, Basel.)

Background: Percutaneous biliary balloon dilation (PBBD) stands as a safe, useful, and inexpensive treatment procedure performed on patients with benign anastomotic stricture of Roux-en-Y hepatojejunostomy (BASH). However, the optimal mode of application is still under discussion., Methods: A retrospective cohort study was conducted including patients admitted between 2008 and 2015 with diagnosis of BASH. Patients were divided into 2 groups: group I (n = 22), included patients treated after the implementation of an institutional protocol of 3 PBBD sessions within a fixed time interval and group II (n = 24) consisted of our historical control of patients who underwent one or 2 dilation sessions. Patency at one-year post procedure was assessed with the classification proposed by Schweizer. Symptomatic response to treatment was analyzed using the Terblanche classification., Results: Patients in group I exhibited more excellent/good results (90 vs. 50%, p = 0.003) and less poor results (5 vs. 42%, p = 0.005) according to the Schweizer classification and more grade I/excellent results according to Terblanche classification (p = 0.003). Additionally, group I showed lower serum total bilirubin (p = 0.001), direct bilirubin (p = 0.002), alkaline phosphatase (p = 0.322), aspartate aminotransferase (p = 0.029), and alanine aminotransferase (p = 0.006)., Conclusion: A protocol of 3 consecutive PBBD sessions within a fixed time interval may yield a high rate of patency, with a positive clinical, biochemical, and radiological impact on patients with BASH., (© 2017 S. Karger AG, Basel.)

Objective: The role of sLOX-1 in acute ischemic stroke still remains unclear. This study aims to demonstrate the value of sLOX-1 in evaluating degrees of intracranial artery stenosis and to predict prognosis in stroke., Methods: Two hundred and seventy-two patients were included in this study and basic data were collected within 72 hr on admission. We assessed the association between sLOX-1 levels and stroke conditions in one-year duration. After adjusting for potential confounders, regression analyses were performed., Results: We found that sLOX-1 levels were increased significantly in severe patients compared to the mild stroke group ( p  = .011). After adjusting confounders, sLOX-1 was associated with a poor functional outcome in patients with an adjusted OR of 2. 946 (95% CI, 1.788-4.856, p  < .001). There was also positive correlation between sLOX-1 levels and the degrees of intracranial artery stenosis in the different groups ( p  = .029)., Conclusions: Our study demonstrated that sLOX-1 levels could be used to evaluate the severity of stroke and the degrees of intracranial artery stenosis. Furthermore, sLOX-1 could be exploited to predict the long-term functional outcome of stroke.

Biliary stricture is a common cause of morbidity after liver transplantation (LT). This study aimed to determine the risk factors for post-transplant biliary anastomotic strictures (BAS), focusing on perioperative platelet counts. We enrolled 771 consecutive recipients who underwent ABO-identical/compatible deceased donor LT with duct-to-duct biliary reconstruction from January 2000 to June 2012. BAS was identified in 142 cases. The median time for stricture development was 176 days. Preoperative and postoperative platelet counts within 5 days after LT were significantly lower in patients with BAS than those without BAS. Using cutoff values acquired by the receiver operating characteristic curve analysis, persistent postoperative thrombocytopenia was defined as platelet counts <41 × 1000/μl and <53 × 1000/μl on postoperative day (POD) 3 and POD 5, respectively. Multivariate analysis indicated persistent postoperative thrombocytopenia (OR = 2.38) was the only independent risk factor for BAS. No significant associations were observed in terms of donor and surgical factors. Multivariate analysis demonstrated estimated blood loss (OR = 1.01, per 100 ml) was an independent contributing factor for persistent postoperative thrombocytopenia. We demonstrated low platelet count was associated with progression of post-transplant BAS. Minimizing intraoperative blood loss potentially contributes to maintain post-transplant platelet count, which may reduce incidence of BAS., (© 2017 Steunstichting ESOT.)

Background: Several myokines are produced by cardiac muscle. We investigated changes in myokine levels at the time of acute myocardial infarction (MI) and following reperfusion in relation to controls., Methods: Patients with MI (MI Group, n=31) treated with percutaneous coronary intervention (PCI) were compared to patients with stable coronary artery disease (CAD) subjected to scheduled PCI (CAD Group, n=40) and controls with symptoms mimicking CAD without stenosis in angiography (Control Group, n=43). The number and degree of stenosis were recorded. Irisin, follistatin, follistatin-like 3, activin A and B, ALT, AST, CK and CK-MB were measured at baseline and 6 or 24h after the intervention., Results: MI and CAD patients had lower irisin than controls (p<0.001). MI patients had higher follistatin, activin A, CK, CK-MB and AST than CAD patients and controls (all p≤0.001). None of the myokines changed following reperfusion. Circulating irisin was associated with the degree of stenosis in all patients (p=0.05). Irisin was not inferior to CK-MB in predicting MI while folistatin and activin A could discriminate MI from CAD patients with similar to CK-MB accuracy. None of these myokines was altered following PCI in contrast to CK-MB., Conclusions: Irisin levels are lower in MI and CAD implying that their production may depend on myocadial blood supply. Follistatin and activin A are higher in MI than in CAD suggesting increased release due to myocardial necrosis. They can predict MI with accuracy similar to CK-MB and their role in the diagnosis of MI remains to be confirmed by prospective large clinical studies., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Intestinal stricture is a severe and common complication of necrotizing enterocolitis (NEC), causing severe and prolonged morbidity. Our goal was to investigate the clinical predictors for strictures developing after NEC and evaluate the management outcome of the post-NEC strictures to better orient their medicosurgical care.A total of 188 patients diagnosed with NEC with identical treatment protocols throughout the period under study were retrospectively reviewed from 4 academic neonatal centers between from January 1, 2011, and October 31, 2016. Clinical predictive factors and clinical outcomes, including demographic information, clinical management, laboratory data, histopathology of resected bowel segment, and discharge summaries, were evaluated on the basis of with post-NEC strictures or not.Of the involved variables examined, the late-onset NEC [risk ratio (RR), 0.56; 95% confidence interval (95% CI), 0.41-0.92; P < 0.001], cesarean delivery (RR, 1.42; 95% CI, 0.98-2.29; P = 0.026), and first procalcitonin (PCT) (onset of symptoms) (RR, 1.82; 95% CI, 0.98-3.15; P = 0.009) were the independent predictive factors for the post-NEC strictures. C-reactive protein (CRP), white blood cell (WBC), and plateletcrit levels were markedly higher on infants with stricture and elevated levels were maintained until the stricture was healed. Infants with intestinal stricture had significantly longer times to beginning enteral feeds (23.9 ± 12.1), than infants without intestinal stricture (18.6 ± 8.8) (P = 0.023). The median age at discharge was also significantly higher in the group with stricture (P = 0.014).This retrospective and multicenter study demonstrates that the early-onset NEC and cesarean delivery conferred protection over the post-NEC stricture. Infants with post-NEC stricture need prolonged hospitalization.

Background: Carcinoembryonic antigen (CEA) can be used to screen for biliary tract cancer in patients with primary sclerosing cholangitis (PSC)., Aim: To study the influence of benign dominant strictures (DS), superimposed bacterial cholangitis (SBC), smoking status, and inflammatory bowel disease on CEA serum levels., Methods: A retrospective analysis of CEA values in cancer-free PSC patients was performed. We included the maximal CEA value obtained during follow-up and information on the presence of DS and SBC at that time, and we analyzed the CEA values in the presence and absence of DS and SBC. Results are reported as medians with the interquartile range (IQR)., Results: The median maximal CEA level, which was 1.8 ng/mL (IQR 1.2-2.9) in the final 270 PSC patients included in the study, was not influenced by the presence of either DS or SBC (P = 0.320). Moreover, in 49 patients, the first CEA value available at the time of DS (1.5 ng/mL; IQR 1.2-2.1) and that at a time without DS (1.6 ng/mL; IQR 1.1-2.3) did not differ significantly (P = 0.397). Lastly, in 24 patients, the median CEA values at a time without SBC (1.8 ng/mL; IQR 1.2-2.5) and at the time of SBC (1.8 ng/mL; IQR 1.0-3.0) were comparable (P = 0.305). Smoking did not influence CEA-based cancer screening., Conclusions: Serum CEA level is not influenced by the presence of DS or SBC and might therefore serve as a favorable parameter for improving cancer screening in PSC patients.

Biliary stenosis is a common complication after liver transplantation, and has an incidence rate ranging from 4.7% to 12.5% based on our previous study. Three types of biliary stenosis (anastomotic stenosis, non-anastomotic peripheral stenosis and non-anastomotic central hilar stenosis) have been identified. We report the outcome of two patients with anastomotic stricture after liver transplantation who underwent successful cutting balloon treatment. Case 1 was a 40-year-old male transplanted due to subacute fulminant hepatitis C. Case 2 was a 57-year-old male transplanted due to hepatitis B virus-related end-stage cirrhosis associated with hepatocellular carcinoma. Both patients had similar clinical scenarios: refractory anastomotic stenosis after orthotopic liver transplantation and failure of balloon dilation of the common bile duct to alleviate biliary stricture.

Background and Objectives: Inflammation is relevant in restenosis of atherosclerotic vascular diseases, but its role in dialysis arteriovenous fistula remains unknown. In animal studies, upregulation of monocyte chemoattractant protein-1 has been shown in venous segments of arteriovenous fistula. We, therefore, aimed to investigate serial changes in circulating monocyte chemoattractant protein-1 after percutaneous transluminal angioplasty of dialysis arteriovenous fistulas and its relation to restenosis., Design, Setting, Participants, & Measurements: Fifty-nine patients with dysfunctional arteriovenous fistulas that were referred for percutaneous transluminal angioplasty were enrolled prospectively between January of 2010 and July of 2012. Three of them were excluded due to percutaneous transluminal angioplasty failure or acute infection. Blood was sampled from arteriovenous fistulas at baseline, 2 days, 2 weeks, and 3 months after percutaneous transluminal angioplasty. Clinical follow-up was continued monthly for 3 months. Angiographic follow-up was arranged at the end of 3 months. Seventeen patients without significant stenosis were enrolled as the control group., Results: Fifty-six patients completed clinical follow-up. Significant increases in monocyte chemoattractant protein-1 were observed at 2 days and 2 weeks (both P<0.001) after percutaneous transluminal angioplasty. Twenty-three (41%) patients had symptomatic restenosis. The restenosis group had a higher percentage change in monocyte chemoattractant protein-1 levels at 2 days (median =47%; interquartile range, 27%-65% versus median =17%; interquartile range, 10%-25%; P<0.001) after percutaneous transluminal angioplasty compared with the patent group. Fifty-two patients completed angiographic follow-up. A positive correlation between relative luminal loss and monocyte chemoattractant protein-1 increase at 2 days after percutaneous transluminal angioplasty was found (r=0.53; P<0.001). In multivariate analysis, postangioplasty monocyte chemoattractant protein-1 increase at 2 days was an independent predictor of restenosis. Using receiver operator characteristic analysis, >25% postangioplasty increase of monocyte chemoattractant protein-1 was significantly associated with restenosis after percutaneous transluminal angioplasty (hazard ratio, 5.36; 95% confidence interval, 1.81 to 15.8)., Conclusions: Circulating monocyte chemoattractant protein-1 levels were elevated 2 days and 2 weeks after percutaneous transluminal angioplasty. Early postangioplasty increase of monocyte chemoattractant protein-1 level was associated with restenosis of arteriovenous fistulas., (Copyright © 2016 by the American Society of Nephrology.)

Background and Study Aims: The diagnosis of cholangiocarcinoma (CCA) is difficult. The present study aimed to assess the clinical features, diagnosis, and survival in CCA., Patients and Methods: This is a prospective study on 46 patients with CCA who underwent endoscopic retrograde cholangiopancreatography (ERCP) or surgical resection and 20 controls with a clinical and ERCP suspicion for CCA in whom surgical biopsy and/or 4-year follow-up showed a benign biliary stricture., Results: The median age at presentation was 71years (range 44-88). Thirty-four patients (73.9%) presented with painless jaundice. Median CA 19-9 value was 188IU/L (range 1-49,138), with a level of <100IU/L in 13 patients (28%). Total bilirubin was 11.9 (0.6-36.3)mg/dL. The tumour was intrahepatic in 3 (6.5%), hilar (Klatskin) in 25 (54.3%), and located in the lower third of the bile duct in 18 (39.1%) patients. The diagnosis was confirmed by positive cytology in 10 (21.7%), biopsy in 20 (43.5%), cholangioscopy in five (10.9%), and imaging and clinical grounds in 11 (23.9%) patients. Cytology was feasible in 36 patients; it was positive in 10 and "highly indicative" in two patients (33.3% sensitivity). Twenty-two patients (47.8%) were treated by surgical resection, and the rest were offered palliative biliary drainage. Mean estimated survival for the entire group of CCA patients was 21.5±3.3months. Survival was slightly longer in patients who underwent surgical resection than those who had palliative treatment; the estimated mean survival rates were 26.2±4.2 vs. 17.1±3.3months, respectively, but the difference was not statistically significant (p=0.115)., Conclusion: The diagnosis of CCA is difficult and often delayed. The outcome is generally poor., (Copyright © 2016 Pan-Arab Association of Gastroenterology. Published by Elsevier B.V. All rights reserved.)

Measurements of the hemodynamic information of blood flows, especially wall shear stress (WSS), in animal models with circulatory vascular diseases (CVDs) are important to understand the pathological mechanism of CVDs. In this study, X-ray particle image velocimetry (PIV) with high spatial resolution was applied to obtain velocity field information in stenosed blood vessels with high WSS. 3D clips fabricated with a 3D printer were applied to the abdominal aorta of a rat cadaver to induce artificial stenosis in the real blood vessel of an animal model. The velocity and WSS information of blood flows in the stenosed vessel were obtained and compared at various stenosis severities. In vivo measurement was also conducted by fastening a stenotic clip on a live rat model through surgical intervention to reduce the flow rate to match the limited temporal resolution of the present X-ray PIV system. Further improvement of the temporal resolution of the system might be able to provide in vivo measurements of hemodynamic information from animal disease models under physiological conditions. The present results would be helpful for understanding the relation between hemodynamic characteristics and the pathological mechanism in animal CVD models.

Intracranial arterial stenosis (ICAS) is an important cause of ischemic stroke and transient ischemic attack (TIA), and the correlation between the plasma non-high density cholesterol (non-HDLC) levels and ICAS, especially asymptomatic ICAS (AICAS) is not clear. The Asymptomatic Polyvascular Abnormalities Community(APAC) study is a community-based, prospective, long-term follow-up observational study. 3387 participants were enrolled in this study. The diagnosis of AICAS was made by transcranial Doppler ultrasonography. The participants were then divided into 3 groups based on their non-HDLC levels. The cox regression was used to analyze the correlation between the non-HDLC level and the incidence of AICAS.9.98% of the participants were diagnosed with AICAS during 2 years following up. Multivariate analysis showed that non-HDL-C is an independent indicator for the incidence of AICAS (HR = 1.22, 95%CI: 1.06-1.40), The incidence of AICAS gradually increase with the increasing non-HDLC level. Compared with subgroup(non-HDLC < 3.4 mmol/l), incidence of AICAS was significantly higher in the subgroups(non-HDLC 3.4-4.1 mmol/l and non-HDLC ≥ 4.1 mmol/l) after adjustment for the confounding factors (HR = 1.32, 95%CI:1.02-1.73; HR = 1.46, 95%CI: 1.10-1.94, respectively). In conclusions, our findings suggest that elevated non-HDLC levels a significant risk factor for the development of AICAS in the APAC study.

Objectives: Intracranial atherosclerotic stenosis (ICAS) is one of the most common causes of stroke worldwide and, in particular, has been implicated as a leading cause of recurrent ischemic stroke. We adapted a rat model of atherosclerosis to study brain intracranial atherosclerosis, and further investigated the effect of omega-3 fatty acids (O3FA) in attenuating development of ICAS., Materials and Methods: Adult male Sprague-Dawley rats were divided into control normal-cholesterol or high-cholesterol diet groups with or without O3FA for up to 6weeks. During the first 2weeks, NG-nitro-l-arginine methyl ester (l-NAME, 3mg/mL) was added to the drinking water of the high-cholesterol groups. The rats received supplementation with O3FA (5mg/kg/day) by gavages. Blood lipids including low density lipoprotein (LDL), cholesterol (CHO), triglycerides (TG) and high density lipoprotein (HDL) were measured at 3 and 6weeks. The lumen of middle cerebral artery (MCA) and the thickness of the vessel wall were assessed. Inflammatory molecular markers were assessed by Western blot., Results: A high-cholesterol diet exhibited a significant increase in the classic blood markers (LDL, CHO, and TG) for atherosclerosis, as well as a decrease in HDL. These markers were found to be progressively more severe with time. Lumen stenosis and intimal thickening were increased in MCA. O3FA showed attenuation of blood lipids with an absence of morphological changes. O3FA significantly reduced the inflammatory marker CD68 in MCA and prevented monocyte chemotactic protein (MCP-1) and interferon-γ (IFN-γ) expression in the brain. O3FA similarly decreased inducible nitric oxide synthase (iNOS), tumor necrosis factor alpha (TNF-α), and interleukin 6 (IL-6), markers affiliated with monocyte activity in atherosclerosis. Furthermore, O3FA significantly inhibited the expression of vascular cell adhesion molecule-1 (VCAM-1), a marker for endothelial activation. Lastly, O3FA increased ATP-binding cassette transporter A1 (ABCA1) protein expression via silent information regulator 1 (SIRT1) activation, thus increasing cholesterol efflux from macrophages to HDL., Conclusions: Long-term O3FA dietary supplementation prevents the development of intracranial atherosclerosis. This O3FA effect appears to be mediated by its prevention of macrophage infiltration into the vessel wall, therefore reducing inflammation and intimal thickening. While similar effects in humans need to be determined, O3FA dietary supplement shows promising results in the prevention of ICAS., (Copyright © 2016 IBRO. Published by Elsevier Ltd. All rights reserved.)

Mortality rates associated with off‑pump coronary artery bypass (CAB) are relatively high, as the majority of patients requiring CAB are at a high risk for cardiac events. The present study aimed to establish porcine models of acute myocardial ischemia, and evaluate the protective role of shunt and active perfusion. A total of 30 pigs were randomly assigned to five groups, as follows: i) Sham (control); ii) A1 (shunt; stenosis rate, 55%); iii) A2 (shunt; stenosis rate, 75%); iv) B1 (active perfusion; stenosis rate, 55%); and v) B2 (active perfusion; stenosis rate, 75%) groups. Aortic pressure (P0), left anterior descending coronary pressure (P1), and coronary effective perfusion pressure (P1/P0) were measured. The expression levels of tumor necrosis factor‑α (TNF‑α), cardiac troponin (cTnI), creatine kinase‑myocardial band (CK‑MB), interleukin (IL)‑6, IL‑10, B‑cell lymphoma 2 (Bcl‑2), and caspase‑3 were detected using enzyme‑linked immunosorbent assay or western blotting. The myocardial apoptosis rate was determined using the terminal deoxynucleotidyl transferase dUTP nick end labeling assay. Ischemia models with stenosis rates of 55 and 75% were successfully constructed following suturing of the descending artery. Compared with the control, the 55 and 75% stenosis groups demonstrated significantly decreased P1/P0, increased expression levels of TNF‑α, cTnI, CK‑MB, IL‑6, IL‑10 and caspase‑3, an increased rate of myocardial apoptosis, and a decreased expression level of anti‑apoptotic protein, Bcl‑2. At 30 min following successful establishment of the model (ST segment elevation to 1 mm), group B demonstrated significantly increased P1/P0, decreased expression levels of TNF‑α, cTnI, CK‑MB, IL‑6, IL‑10 and caspase‑3, a decreased rate of myocardial apoptosis, and an increased expression level of anti-apoptotic protein, Bcl‑2. Furthermore, the current study indicated that active perfusion was more efficacious in maintaining myocardial perfusion and alleviating ischemic injury when compared with traditional shunt perfusion.

The unsteady flow characteristics of blood are analyzed through a catheterized stenotic artery with post-stenotic dilatation. A rigid tube with a pair of abnormal wall segments in close proximity to each other is employed to geometrically simulate the diseased artery. A micropolar fluid model is used to capture the rheological characteristics of the streaming blood in the annulus. The mild stenosis approximation is employed to derive the governing flow equation which is then solved using a robust finite difference method. Particular attention is paid to the effects of geometrical parameters of the arterial wall and rheological parameters of the blood on axial velocity, flow rate, resistance impedance and wall shear stress. The global behavior of blood is also analyzed through instantaneous pattern of streamlines.

Unlabelled: The pathogenesis of intrahepatic biliary stricture formation in patients with primary sclerosing cholangitis (PSC) or after liver transplantation (LTx) remains elusive. CD14 receptor signaling is a key mediator of the innate immune system; its common genetic variant is associated with alcoholic liver disease. PSC and LTx cohort patients and primary biliary cirrhosis (PBC) control patients were genotyped for the CD14 -260C>T (rs2569190) polymorphism, and genotypes were correlated with long-term clinical outcome. Biliary tissue, bile, and whole blood of PSC patients and healthy controls were screened for markers of the innate immune system and bacterial infection. In 121 PSC patients, the CD14 -260C>T genotype was associated with development of dominant bile duct strictures (P = 0.02). In 365 LTx patients, TT carriers (4.1%) were protected against the formation of nonanastomotic biliary strictures versus CC/CT patients (12.6%; P = 0.01). Chemokine ligand 8 (P = 0.04) and chemokine receptor 6 (P = 0.004) were up-regulated in biliary tissue of PSC patients with the TT versus the CC/CT genotype. Lipopolysaccharide whole-blood stimulation resulted in a significant change in interleukin (IL)-8 (P = 0.05) and IL-12p40 levels (P = 0.04) in healthy control subjects carrying the TT genotype. TT PSC patients were protected against Gram-negative bacterial biliary infection (TT: 0% vs., Cc/ct: 22.5%; P = 0.02). Serum-soluble CD14 levels correlated with the CD14 -260C>T genotype (P = 0.02), representing an independent risk indicator of survival in PSC patients (hazard ratio, 0.40; 95% confidence interval, 0.19-0.86; P =0.01)., Conclusions: The function of the innate immune response by CD14 is crucial during biliary infection and stricture formation. The benefits of CD14 signaling modification should be addressed in future studies. (Hepatology 2016;64:843-852)., (© 2016 by the American Association for the Study of Liver Diseases.)

Unlabelled: Essentials A consensus methodology for assessing the effects of antiplatelet agents has not been established. Measuring platelet thrombus formation (PTF) for evaluating antiplatelet effects was assessed. PTF differentially reflected antiplatelet effects compared to other tests. PTF may be associated with the severity of carotid or intracranial arterial stenosis. Click to hear a presentation on platelet function testing in the clinic by Gresele and colleagues, Summary: Background A consensus methodology for assessing the effects of antiplatelet agents has not been established. Objective We investigated the usefulness of directly measuring platelet thrombus formation (PTF) using a microchip-based flow chamber system for evaluating antiplatelet therapy. Patients/Methods Platelet thrombus formation in the whole blood of 94 patients with ischemic cerebrovascular disease treated with clopidogrel and/or aspirin was measured in a flow chamber system at a shear rate of 1500 s(-1) and was compared with the results of assays for agonist-induced platelet aggregability, phosphorylation of vasodilator-stimulated phosphoprotein, platelet p-selectin expression (PS), and platelet-monocyte complexes. Results In all patients tested, area under the flow pressure curve (AUC10), which represents platelet thrombogenicity, showed weak correlation with platelet aggregation induced by either adenosine diphosphate or collagen. In addition, AUC10 was lower in patients treated with dual antiplatelet therapy (median 79.4) compared with patients treated with aspirin or clopidogrel alone (217.7 and 301.0, respectively), whereas the parameters evaluated by the other assays did not reflect the combined treatment efficacy. In clopidogrel monotherapy patients, AUC10 was associated with the severity of arterial stenosis (R(2) = 0.127, β = 1.25), and AUC10 and PS were higher in patients with severe carotid or intracranial arterial stenosis than in those with mild stenosis. Conclusions Platelet thrombus formation measurement using a flow-chamber system was useful for evaluating the efficacy of treatment with aspirin and clopidogrel, both alone and in combination. The present findings indicate that high residual platelet thrombogenicity in patients treated with clopidogrel may be associated with the severity of carotid or intracranial arterial stenosis., (© 2016 International Society on Thrombosis and Haemostasis.)

Introduction: Abnormal glucose metabolism is an independent risk factor for poor outcome following acute ischemic stroke. However, the relationship between initial hemoglobin A1c level and functional outcome (defined by modified Rankin Scale scores) following small-artery occlusion, a subtype of ischemic stroke, is unknown. The aim of the present study was to evaluate this association among patients diagnosed with small-artery occlusion., Materials and Methods: Data on 793 patients diagnosed with small-artery occlusion from October 25, 2012 to June 30, 2015 were collected from the stroke registry of the Department of Neurorehabilitation of HuanHu Hospital. Hemoglobin A1c values at admission were classified into three groups according to tertiles (<5.9,5.9to<6.7, and≥6.7). We used receiver operating characteristics curves to investigate the predictive value of hemoglobin A1c and examined the relationship between hemoglobin A1c levels at admission and modified Rankin Scale scores using univariate and multivariate analyses., Results: The area under the curve was 0.570 (95%CI, 0.509-0.631; P = 0.023). Patients in the highest HbA1c stratification (≥6.7) had a significantly higher risk of an unfavorable outcome than patients in the lowest stratification (<5.9; adjusted odds ratio, 2.099; 95%CI, 1.160-3.798; P = 0.014). However, a significant association was not seen in the middle stratification (5.9 to <6.7; P = 0.115)., Conclusions: Elevated hemoglobin A1c level on admission was adversely associated with functional outcomes 3 months after stroke onset among patients presenting with small-artery occlusion.

Exercise-induced dyspnea is common among adolescents and young adults and often originates from exercise-induced bronchoconstriction (EIB). Sometimes, dyspnea corresponds to exercise-induced laryngospasm (EILO), which is a paradoxical decrease in supraglottic/glottic area. Vitamin D deficiency, which occurs frequently at northern latitudes, might favor laryngospasm by impairing calcium transport and slowing striate muscle relaxation. The aim of this study was to evaluate whether vitamin D status has an influence on bronchial and laryngeal responses to exercise in young, healthy athletes. EIB and EILO were investigated during winter in 37 healthy competitive rowers (24 males; age range 13-25 years), using the eucapnic voluntary hyperventilation test (EVH). EIB was diagnosed when forced expiratory volume in the first second decreased by 10%, EILO when maximum mid-inspiratory flow (MIF50) decreased by 20%. Most athletes (86.5%) had vitamin D deficiency (below 30 ng/mL), 29 mild-moderate (78.4%) and 3 severe (8.1%). EVH showed EIB in 10 subjects (27%), EILO in 16 (43.2%), and combined EIB and EILO in 6 (16.2%). Athletes with EILO had lower vitamin D (19.1 ng/mL vs. 27.0 ng/mL, p < 0.001) and higher parathyroid hormone (30.5 pg/mL vs. 19.2 pg/mL, p = 0.006) levels. The degree of laryngoconstriction (post-EVH MIF50 as a percentage of pre-EVH MIF50) was related directly with vitamin D levels (r = 0.51; p = 0.001) and inversely with parathyroid hormone levels (r = -0.53; p = 0.001). We conclude that vitamin D deficiency is common during winter in young athletes living above the 40th parallel north and favors laryngospasm during exercise, probably by disturbing calcium homeostasis. This effect may negatively influence athletic performance.

Serum biochemical indices reflect dynamic physiological and pathophysiological processes within the body, the associations between these markers and the number of stenotic coronary arteries have been rarely studied. 627 healthy controls and 1,049 coronary heart disease (CHD) patients were sequentially recruited in our hospital. The association patterns between serum biochemical markers and the numbers of stenotic coronary arteries were evaluated in a cross-sectional manner. Upon binary multiple logistic regression analysis, the risk factor patterns differed by gender. Age, high-density lipoprotein cholesterol (HDL) and homocysteine (HCY) were common risk factors for CHD in both males and females. Upon ordinal multiple logistic regression analysis, age, low-density lipoprotein cholesterol (LDL) and lipoprotein (Lp) (a) increased, and HDL decreased, as the number of stenotic coronary arteries increased in male patients. Age and Lp(a) were positively associated with the number of stenotic coronary arteries and total bilirubin (TBil) was negatively associated with the number of stenotic coronary arteries in female patients. Age and Lp(a) were common risk factors positively associated with the number of stenotic coronary arteries in both male and female patients. HDL and LDL were male-specific risk factors and TBil was a female-specific risk factor for an increasing number of stenotic coronary arteries. In conclusion, serum biomarker levels correlated with the number of stenotic coronary arteries and showed gender different patterns., Competing Interests: The authors have declared that no conflict of interest exists.

Objective: To explore the potential damaging effect of chronic pelvic inflammation on ovarian reserve., Design: Case-control study., Patients: A total of 122 women with bilateral tubal occlusion, diagnosed by hysterosalipingography (HSG) and 217 women with normal fallopians were recruited., Measurements: Serum anti-Mullerian hormone (AMH), basic follicle-stimulating hormone (FSH), luteining hormone (LH), estradiol (E2), and testosterone (T) were measured; and antral follicle counts (AFCs) were recorded., Results: Significantly lower level of AMH was observed in women with bilateral tubal occlusion compared to control group [2.62 (2.95) ng/ml vs. 3.37 (3.11) ng/ml, P = 0.03], and the difference remained after adjustment of BMI (Padjust = 0.04). However, no statistical difference was found in the levels of FSH [7.00 (2.16) IU/L vs. 6.74 (2.30) IU/L], LH [4.18 (1.52) IU/L vs. 4.63 (2.52) IU/L], E2 [35.95 (20.40) pg/ml vs. 34.90 (17.85) pg/ml], T [25.07±11.46 ng/dl vs. 24.84±12.75 ng/dl], and AFC [6.00 (4.00) vs. 7.00 (4.00)] between two groups (p>0.05)., Conclusions: Women with bilateral tubal occlusion showed decreased AMH level, suggesting that chronic pelvic inflammation may diminish ovarian reserve. More caution should be paid when evaluating the detriment of PID on female fertility.

Introduction: Although hepatic vein stenosis after liver transplantation is a rare complication, the complication rate of 1% to 6% is higher in pediatric living-donor liver transplantation than that in other liver transplantation cases. Diagnosis is very important because this complication can cause hepatic congestion that develops to liver cirrhosis, graft loss, and patient loss. However, this is unlikely in cases where there are no ascites or hypoalbuminemia., Objectives: Eleven of 167 patients who had undergone pediatric living-donor liver transplantation were identified in the outpatient clinic at Jichi Medical University as having suffered from hepatic vein stenosis, and were enrolled in the study., Methods: We conducted a retrospective study in which we reviewed historical patient records to investigate the parameters for diagnosis and examine treatment methods and outcomes., Results: The 11 patients were treated with 16 episodes of balloon dilatation. Three among these received retransplantation and another 2 cases required the placement of a metallic stent at the stenosis. Histological examination revealed severe fibrosis in four of nine patients who had a liver biopsy, with mild fibrosis revealed in the other five grafts. Furthermore, hepatomegaly and splenomegaly diagnosed by computed tomography, elevated levels of hyarulonic acid, and/or a decrease in calcineurin inhibitor clearance were found to be pathognomonic at diagnosis, and tended to improve after treatment., Conclusions: Diagnosis of hepatic vein stenosis after liver transplantation can be difficult, so careful observation is crucial to avoid the risk of acute liver dysfunction. Comprehensive assessment using volumetry of the liver and spleen and monitoring of hyarulonic acid levels and/or calcineurin inhibitor clearance, in addition to some form of imaging examination, is important for diagnosis and evaluation of the effectiveness of therapy., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Biliary obstruction is a common clinical manifestation of various conditions, including extrahepatic cholangiocarcinoma. However, a screening test for diagnosis of extrahepatic cholangiocarcinoma in patients with biliary obstruction is not yet available. According to the rationale that the biliary system plays a major role in lipid metabolism, biliary obstruction may interfere with lipid profiles in the body. Therefore, plasma lipidomics may help indicate the presence or status of disease in biliary obstruction suspected extrahepatic cholangiocarcinoma. This study aimed to use plasma lipidomics for diagnosis of extrahepatic cholangiocarcinoma in patients with biliary obstruction. Plasma from healthy volunteers, patients with benign biliary obstruction extrahepatic cholangiocarcinoma, and other related cancers were used in this study. Plasma lipids were extracted and lipidomic analysis was performed using matrix-assisted laser desorption ionization time-of-flight mass spectrometry. Lipid profiles from extrahepatic cholangiocarcinoma patients showed significant differences from both normal and benign biliary obstruction conditions, with no distinction between the latter two. Relative intensity of the selected lipid mass was able to successfully differentiate all extrahepatic cholangiocarcinoma samples from patient samples taken from healthy volunteers, patients with benign biliary obstruction, and patients with other related cancers. In conclusion, lipidomics is a non-invasive method with high sensitivity and specificity for identification of extrahepatic cholangiocarcinoma in patients with biliary obstruction.

Background: Osteoprotegerin (OPG) is a member of the tumor necrosis factor receptor superfamily and suggested as a marker of atherosclerosis. However, little is known about the association between plasma OPG levels and lower extremity arterial disease. We investigated whether plasma OPG levels were associated with the presence and severity of lower extremity arterial disease in patients with type 2 diabetes., Methods: This was a study of 712 patients with type 2 diabetes aged 40 years or older. Plasma OPG was measured using ELISA. The lower extremity arterial disease was diagnosed by high-frequency color Doppler ultrasonic., Results: Of 712 patients, 505 (70.9 %) had lower extremity arterial stenosis. OPG levels were significantly increased in patients with lower extremity arterial stenosis [1.89 (1.48-2.41) vs. 2.39 (1.82-3.33) ng/mL, p < 0.001]. Plasma OPG levels increased gradually with increasing severity of lower extremity arterial stenosis (p < 0.001 for trend), after adjustment for traditional cardiovascular risk factors such as age, gender, smoking, total cholesterol, high-density lipoprotein (HDL) cholesterol, C-reactive protein (CRP), body mass index (BMI), systolic blood pressure(SBP). The risk of lower extremity arterial disease was increased (OR = 1.17, 95 % CI 1.09 -1.28, p < 0.001) with each standard deviation (SD) higher level of OPG in patients with type 2 diabetes after adjustment for traditional CVD risk factors., Conclusions: Plasma OPG levels were significantly associated with the presence and severity of lower extremity arterial disease. Our results suggest that OPG is an important plasma biomarker of lower extremity arterial disease in type 2 diabetes.

Background: Development of fibrosis and subsequent stricture formation in Crohn's disease (CD) increases morbidity and rates of surgery and reduces patients' quality of life. There are currently no biomarkers of intestinal fibrosis that might allow earlier identification and better management of patients at increased risk of stricture formation., Methods: MicroRNA profiling of serum from CD patients was used to identify microRNAs associated with stricture formation. Differential expression of miR-19a-3p and miR-19b-3p was validated by quantitative PCR in independent CD cohort of stricturing and nonstricturing patients (n = 46 and n = 62, respectively). Levels of miR-19a-3p and miR-19b-3p were also quantified in baseline serum samples, and expression compared between CD patients who subsequently developed stricture and those who did not (n = 11 and n = 44, respectively)., Results: Serum levels of miR-19a-3p and miR-19b-3p in the array were lower in CD patients with a stricturing phenotype than in control CD patients (P = 0.007 and 0.008, respectively). The reduction in miR-19a-3p and 19b-3p was verified in a second cohort (P = 0.002). The association of miR-19-3p with stricturing CD was independent of potential confounding clinical variables, including disease duration, disease activity, site, gender, and age. Serum analyses in patients with 4 years of follow-up support the hypothesis that reduced miR-19a-3p and miR-19b-3p predate stricture development with a trend toward significance (P = 0.077 and P = 0.060, respectively)., Conclusions: These data identify miR-19-3p as a potential circulating marker of stricturing CD. Our data show that microRNAs have utility as noninvasive biomarkers of stricturing CD. Further longitudinal studies are required to determine the prognostic value of miR-19-3p at diagnosis.

Background: Crohn's disease (CD) is a form of inflammatory bowel disease with different described behaviors, including stricture. At present, there are no laboratory studies that can differentiate stricturing CD from other phenotypes of inflammatory bowel disease. We performed a pilot study to examine differences in the proteome among patients with stricturing CD, nonstricturing CD, and ulcerative colitis., Methods: Serum samples were selected from the Ocean State Crohn's and Colitis Area Registry, an established cohort of patients with inflammatory bowel disease. Patients with CD with surgically resected stricture were matched with similar patients with CD without known stricture and with ulcerative colitis. Serum samples from each patient were digested and analyzed using liquid chromatography-mass spectrometry to characterize the proteome. Statistical analyses were performed to identify peptides and proteins that can differentiate CD with stricture., Results: Samples from 9 patients in each group (27 total patients) were analyzed. Baseline demographic characteristics were similar among the 3 groups. We quantified 7668 peptides and 897 proteins for analysis. Receiver operating characteristic analysis identified a subset of peptides with an area under the curve greater than 0.9, indicating greater separation potential. Partial least squares discriminant analysis was able to distinguish among the three groups with up to 70% accuracy by peptides and up to 80% accuracy by proteins. We identified the significantly different proteins and peptides and determined their function based on previously published literature., Conclusions: The serum of patients with stricturing CD, nonstricturing CD, and ulcerative colitis is distinguishable through proteomic analysis. Some of the proteins that differentiate the stricturing phenotype have been implicated in complement activation, fibrinolytic pathways, and lymphocyte adhesion.

Background and Purpose: Intracranial arterial stenosis (ICAS) is a common cause of ischemic stroke in Asians, whereas whites tend to have more extracranial lesions. Lipoprotein-associated phospholipase A2 (Lp-PLA2) has been associated with ischemic stroke by a large amount of work. However, there are few studies focusing on the relationship of Lp-PLA2 and asymptomatic ICAS or extracranial arterial stenosis (ECAS). Wehereby sought to explore the relationship of Lp-PLA2 and ICAS, ECAS and concurrent stenosis in stroke-free hypertensive patients in Chinese population., Methods: All the subjects were evaluated for the presence and severity of ICAS and ECAS through computerized tomographic angiography (CTA) covered the whole brain down to the level of aortic arch. Lp-PLA2 mass was measured by enzyme linked immunoassay. The association of Lp-PLA2 and vascular stenosis was analyzed through multivariate logistic regression., Results: Among 414 participants, 163 (39.4%) had no ICAS or ECAS, 63 (15.2%) had ECAS only, 111 (26.8%) had ICAS only and 77 (18.6%) had concurrent extraintracranial stenosis. Lp-PLA2 mass was significantly associated with isolated ICAS (OR: 2.3; 95% CI: 1.14-4.64), and concurrent stenosis (OR: 3.93; 95% CI: 1.62-9.51), but was not related to isolated ECAS (OR: 1.54; 95% CI: 0.68-3.48). Lp-PLA2 mass was also associated with moderate to severe ICAS no matter how was the ECAS. Moreover, patients with higher Lp-PLA2 mass showed more sever ICAS and had more intracranial arterial lesions., Conclusion: This study revealed the association of Lp-PLA2 mass with ICAS in stroke-free hypertensive patients in Chinese population. The further long-term cohort study was warranted to elucidate the concrete effect of Lp-PLA2 on the asymptomatic ICAS.

Orthotopic liver transplantation (OLT) with donation after circulatory death (DCD) often leads to a higher first week peak alanine aminotransferase (ALT) and a higher rate of biliary nonanastomotic strictures (NAS) as compared to donation after brain death (DBD). This retrospective study was to evaluate whether an association exists between peak ALT and the development of NAS in OLT with livers from DBD (n = 399) or DCD (n = 97) from two transplantation centers. Optimal cutoff value of peak ALT for risk of development of NAS post-DCD-OLT was 1300 IU/l. The 4-year cumulative incidence of NAS after DCD-OLT was 49.5% in patients with a high ALT peak post-OLT, compared with 11.3% in patients with a low ALT peak. (P < 0.001). No relation between peak ALT and NAS was observed after DBD-OLT. Multivariate analysis revealed peak ALT ≥1300 IU/l [adjusted hazard ratio (aHR) = 3.71, confidence interval (CI) (1.26-10.91)] and donor age [aHR = 1.04, CI 1.00-1.07] to be independently associated with development of NAS post-DCD-OLT. A peak ALT of <1300 IU/l carries a risk for NAS similar to DBD-OLT. Thus, in DCD-OLT, but not in DBD-OLT, peak ALT discriminates patients at high or low risk for NAS., (© 2015 Steunstichting ESOT.)