atrogenic coronary ostial stenosis (ICOS) following aortic valve replacement (AVR) is a rare but potentially lethal complication. Stenosis of the left main trunk (LMT) and ostium of the right coronary artery (RCA) after AVR was first described by Roberts and Morrow in 1967 1 and the incidence of this complication following AVR has been estimated as between 1% and 5%. [2][3][4][5][6][7] Clinical symptoms are often severe and may appear within the first 6 months. The underlying cause remains undetermined. To date, the diagnosis has been made by repeat angiography and the usual treatment has been aortocoronary bypass surgery, but recently some cases treated with balloon angioplasty and stenting (percutaneous coronary intervention (PCI)) have been reported. [8][9][10][11][12][13] We present 3 cases of ICOS treated with PCI. Case Reports Case 1A 61-year-old woman with a history of hypertension was referred because of fatigue and dyspnea on exertion. On admission the ECG showed sinus rhythm and left ventricular (LV) hypertrophy. Preoperative coronary angiography demonstrated normal coronary arteries and severe calcific aortic valve stenosis. The echo-Doppler revealed a peak aortic gradient of 90 mmHg, mild aortic regurgitation, and an aortic valve area of 0.7 cm 2 with normal LV function. We performed a modified Bentall procedure with the button technique. The patient's tricuspid valve was thickened, and extremely calcified. Coronary arteries were reconstructed with a full root technique. There was no displacement or flexion of the coronary artery graft during the surgical procedure. Myocardial protection with intermittent direct coronary cold blood cardioplegia was used. The first dose was administered by retrograde infusion from the coronary sinus (retro-cannula, RC014I, 14Fr, 4.7 mm, Edwards), and subsequently by antegrade direct cannulation of both coronary ostia using flexible, balloon-tipped cannulae (coronary perfusion cannula, Polystan). A Freestyle Prima PLUS 19-mm stentless valve (Edwards Lifesciences) was used to replace the native valve and aortic root using the full root technique. The patient made a complete recovery and was discharged on oral warfarin. Two months later she experienced severe chest pain and had a syncopal attack, and was taken to the center by ambulance. On admission the ECG showed transient ST-segment depression of 2 mm in the precordial leads, II, III, and aVF (Fig 1). Physical examination revealed normal prosthetic valve sounds, a grade 4/6 systolic ejection murmur at the right second intercostal space, and absence of rales at the base of the lungs. There was no pedal edema. Echocardiography showed normal function of the left ventricle. Repeat coronary angiography showed severe (75%) LMT stenosis and 90% stenosis of the ostium of the RCA (Fig 2). Coronary bypass surgery was recommended as the first therapeutic option, but was rejected by the patient. For this reason she was scheduled for urgent PCI. On the same day PCI of the RCA was performed using a Runway FR3.5 6F guiding catheter ...

Background and Aim Hypothyroidism might play a crucial role in the pathogenesis of non‐alcoholic fatty liver disease (NAFLD). The association of subclinical hypothyroidism with NAFLD has been inconsistent. The relationship of NAFLD with thyroid function parameters and subclinical hypothyroidism was determined. Methods This cross‐sectional study included 70 patients with subclinical hypothyroidism and 70 controls with euthyroidism matched according to gender, age, and body mass index (BMI). NAFLD was diagnosed via abdominal ultrasonography. The association between NAFLD and subclinical hypothyroidism was analyzed. Results The prevalence of NAFLD was significantly higher in patients with subclinical hypothyroidism than in those with euthyroidism. Multivariate analysis showed that subclinical hypothyroidism was an independent risk factor of NAFLD adjusted by metabolic‐related factors, such as BMI, triglyceride, high‐density lipoprotein‐cholesterol, hypertension, and diabetes. Thyroid‐stimulating hormone (TSH) was an independent risk factor of NAFLD adjusted by the same metabolic‐related factors, but free thyroxine (FT4) was not a risk factor. The FIB‐4 index, a noninvasive marker of liver fibrosis was significantly higher in patients with subclinical hypothyroidism than in those with euthyroidism. Compared with patients with euthyroidism, the proportion of the FIB‐4 index ≥2.67 was significantly higher, and the proportion of the FIB‐4 index <1.30 was lower in patients with subclinical hypothyroidism. Conclusions TSH elevation even within the euthyroid range is an independent risk factor of NAFLD and may influence the progression of liver fibrosis, even with a normal FT4 level.

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Aims/Introduction:  Although the improvement of postprandial hyperglycemia by an alpha‐glucosidase inhibitor (α‐GI) has been associated with a risk reduction of cardiovascular events, the relationship between postprandial hyperglycemia and arterial stiffness has not been well understood. We therefore examined whether ameliorating the postprandial state by α‐GI leads to an improvement in arterial stiffness.Materials and Methods:  A total of 22 patients with type 2 diabetes mellitus were treated with acarbose. Cardio‐ankle vascular index (CAVI) as the arterial stiffness was measured by using a VaSera CAVI instrument before and 12 months after acarbose treatment. Serum high‐sensitivity C‐reactive protein (hs‐CRP), pentraxin‐3 (PTX3) and matrix metalloproteinase (MMP) ‐2, ‐9 were measured at the same time points. Furthermore, circulating peripheral blood mononuclear cells were examined for the frequencies of CD14 positive cells expressing membrane type‐1 MMP (MT1‐MMP) at the single cell level using flow cytometry.Results:  After acarbose treatment, postprandial glucose and glycosylated hemoglobin (HbA1c) were significantly decreased. Serum levels of hs‐CRP, PTX3, MMP‐2 and MMP‐9 were significantly decreased. CAVI showed a significant reduction, although the changes were not significant in blood pressure and heart rate. MT1‐MMP expression was significantly decreased by acarbose treatment. In multivariate analysis, improvement of blood glucose, decrease of PTX3 levels and MT1‐MMP expression were independent predictors of beneficial change in CAVI.Conclusions:  The present study showed that the beneficial effects of acarbose on arterial stiffness are mediated by an improvement of postprandial hyperglycemia and vascular remodeling markers. In conclusion, acarbose treatment might reduce the risk of cardiovascular diseases by altering the arterial stiffness in postprandial hyperglycemic status. (J Diabetes Invest, doi:10.1111/j.2040‐1124.2010.00079.x, 2010)

4070 Background: The NIVOLVE trial was designed to assess the efficacy and safety of nivolumab as an adjuvant therapy for HCC, and to identify biomarkers predictive of recurrence in patients after SR or RFA (Registration # UMIN 000026648). Methods: The trial involved 11 sites and was conducted in patients with HCC who showed a complete response after SR (n = 33) or RFA (n = 22) (ITT). Overall, 53 of 55 patients with Child-Pugh A received nivolumab (240 mg/body every 2 weeks (8 cycles)), followed by nivolumab (480 mg/body every 4 weeks (8 cycles)) within 6 weeks after SR or RFA. The primary endpoint was the 1 year recurrence-free survival rate (RFSR). The key secondary endpoint was RFS. Exploratory biomarker analysis included mutations, copy number alterations, and tumor mutation burden in tumor tissues. Techniques included next generation sequencing, immunohistochemical staining (IHC) of formalin-fixed paraffin-embedded tissues (n = 31, 13 with recurrence and 18 without) for CD8, PD-1, PD-L1, Foxp3, and β-catenin, and ctDNA analysis using pre-nivolumab whole blood by deep sequencing (CAPP-seq; Avenio). Results: The 1-year RFSR and median RFS were 76.7% and 26.0 months (95% confidence interval (CI), 23.9–28.1), respectively, with no difference between SR and RFA. Copy number gains (CNGs) in WNT/β-catenin related genes ( APC, CTNNB1, TCF7L1, TCF7L2) (n = 8) correlated with shorter RFS (positive: 11.8 months vs. negative: not reached [NR]; p = 0.0003). IHC revealed that negative staining for PD-1 (p < 0.0001), a low combined positive score for PD-L1 (p = 0.0113), a low number of CD8+ tumor infiltrating lymphocytes (TILs) (p = 0.0130), and positivity for Foxp3+ cells (p = 0.0076) correlated with recurrence. Treatment-related adverse events (AEs) (n = 53) were as follows: all grades, 68%; grades 3–4 (18.9%); and immune related AEs, 25%. HCC cases with low numbers of CD8+ TILs or cases positive for Foxp3+ cells (n = 16) showed a significantly shorter RFS (16.8 months [95% CI, 8.7–25.1]) than those with high numbers of CD8+ TILs and those positive for PD-1/PD-L1 expression (n = 15) (NR [95% CI,26.2months–NR]) (p < 0.0001). HCC cases with activation of the WNT/β-catenin pathway assessed by IHC (n = 9) showed shorter RFS (17.0 months [95% CI,1.1–26.2]) than those without activation (n = 22) (NR [95% CI,24.7 months–NR]) (p = 0.0191). Patients positive for ctDNA (n = 10) before nivolumab tended to have shorter RFS than those without ctDNA (n = 30) (26.2 vs. NR). There was no correlation between TMB and RFS. Conclusions: The 1 year RFSR and RFS in the NIVOLVE trial were 76.6% and 26.0 months, respectively. No new safety signal was observed. CNG in WNT/β-catenin-related genes, activation of the WNT/β-catenin pathway, the presence of Foxp3+ cells, and low numbers of CD8+ TILs may predict recurrence after SR or RFA with adjuvant nivolumab. Clinical trial information: 000026648.

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These results indicate that post-challenge hyperglycaemia is an independent risk factor for arterial stiffness.

Aim To identify laboratory predictors of histological progression (HP) of primary biliary cholangitis (PBC). Methods Sequential biopsies were carried out on 35 (11.4%) of 308 patients with PBC treated with ursodeoxycholic acid (UDCA). Patients were divided into high γ‐glutamyl transpeptidase (GGT) (n = 18) and low GGT (n = 17) groups, based on the median value of GGT at baseline. Patients were then categorized as showing HP (progressive group, PG) or lacking HP (non‐progressive group, NPG) according to the Scheuer and Nakanuma classifications, with the latter grading liver fibrosis (fibrosis score) and bile duct loss (BDL score). Results According to the Scheuer definition, 12 patients had HP and 23 did not. According to the Nakanuma definition, 8 and 27 patients were in the PG and NPG groups, respectively. The fibrosis and BDL scores progressed in 13 and 8 patients, respectively, whereas 22 and 25 patients did not show HP, respectively. Fisher's exact probability test analysis revealed that the rate of HP using the Nakanuma fibrosis score was significantly higher in the high GGT group compared to the low GGT group (P < 0.05). However, no significant correlation was found between the HP of PBC and the biochemical response to UDCA therapy. Both univariate and multivariate logistic regression analyses indicated that the serum GGT level at baseline is an independent risk factor for an increased Nakanuma fibrosis score. Conclusions The level of serum GGT at baseline is significantly associated with liver fibrosis progression in PBC, and therefore could help to predict the HP of PBC.