Quilty Lesions in the Endomyocardial Biopsies after Heart Transplantation

Background The aim of this study was to investigate the clinical significance of Quilty lesions in endomyocardial biopsies (EMBs) of cardiac transplantation patients. Methods A total of 1190 EMBs from 117 cardiac transplantation patients were evaluated histologically for Quilty lesions, acute cellular rejection, and antibody-mediated rejection. Cardiac allograft vasculopathy was diagnosed by computed tomography coronary angiography. Clinical information, including the patients’ survival was retrieved by a review of medical records. Results Eighty-eight patients (75.2%) were diagnosed with Quilty lesions, which were significantly associated with acute cellular rejection, but not with acute cellular rejection ≥ 2R or antibody-mediated rejection. In patient sdiagnosed with both Quilty lesions and acute cellular rejection, the time-to-onset of Quilty lesions from transplantation was longer than that of acute cellular rejections. We found a significant association between Quilty lesions and cardiac allograft vasculopathy. No significant relationship was found between Quilty lesions and the patients’ survival. Conclusions Quilty lesion may be an indicator of previous acute cellular rejection rather than a predictor for future acute cellular rejection

Alagille Syndrome Candidates for Liver Transplantation: Differentiation from End-Stage Biliary Atresia Using Preoperative CT.

PURPOSE:To compare preoperative CT findings before liver transplantation between patients with Alagille syndrome (AGS) and those with end-stage biliary atresia (BA). MATERIALS AND METHODS:The institutional review board approved this retrospective study. Eleven children with AGS (median age, 19.0 ± 13.0 months; male to female ratio, 3:8) and 109 children with end-stage BA (median age, 17.9 ± 25.8 months; male to female ratio, 37:72) who underwent abdomen CT as candidates for liver transplant were included. CT images were reviewed focusing on hepatic parenchymal changes, vascular changes, presence of focal lesions, and signs of portal hypertension. RESULTS:Hepatic parenchymal changes were present in 27% (3/11) of AGS patients and 100% (109/109) of end-stage BA patients (P < .001). The hepatic artery diameter was significantly smaller (1.9 mm versus 3.6 mm, P = 008), whereas portal vein diameter was larger (6.8 mm versus 5.0 mm, P < .001) in patients with AGS compared with patients with end-stage BA. No focal lesion was seen in patients with AGS, whereas 44% (48/109) of patients with end-stage BA had intrahepatic biliary cysts (39%, 43/109) and hepatic tumors (8%, 9/109) (P = .008). Splenomegaly was commonly seen in both groups (P = .082), and ascites (9% [1/11] versus 50% [54/109], P = .010) and gastroesophageal varix (0% [0/11] versus 80% [87/109], P < .001) were less common in patients with AGS than in patients with end-stage BA. CONCLUSION:Fibrotic or cirrhotic changes of the liver, presence of focal lesions, and relevant portal hypertension were less common in patients with AGS than in patients with end-stage BA

Contrast-enhanced axial CT scans for hepatic parenchymal changes.

<p>(A) Normal hepatic morphology in a 7-month-old girl with Alagille syndrome. (B, C) Macroscopic (B) and microscopic (C) specimens of the liver show cholestasis with paucity of interlobular bile duct, but parenchymal destruction is relatively mild (original magnification of microscopic image: x40). (D) Hepatic parenchymal changes with heterogeneous enhancement, fissure widening, left lobe hypertrophy, and periportal edema in a 5-month-old girl with biliary atresia. Note the presence of ascites and gastroesophageal varix. (E, F) Macroscopic (E) and microscopic (F) specimens of the liver show cholestasis and cirrhotic changes with marked parenchymal destruction (original magnification of microscopic image: x40).</p

Contrast-enhanced axial CT scans for vascular changes.

<p>(A) Normal hepatic vasculature in a 5-month-old boy with Alagille syndrome. Diameters of proximal right hepatic artery (arrowhead) and portal vein (thin arrow) are 1.3 mm and 5.0 mm, respectively. The ratio of the hepatic artery diameter to the portal vein diameter is 0.26. (B) Enlarged hepatic artery and small portal vein diameters in a 6-month-old girl with biliary atresia. Diameters of proximal right hepatic artery (arrowhead) and portal vein (thin arrow) are 2.4 mm and 2.6 mm, respectively. The ratio of the hepatic artery diameter to the portal vein diameter is 0.92.</p

Major clinical features and gene analyses in 11 patients with Alagille syndrome candidates for liver transplantation.

<p>Major clinical features and gene analyses in 11 patients with Alagille syndrome candidates for liver transplantation.</p

CT imaging findings in patients with Alagille syndrome and end-stage biliary atresia.

<p>CT imaging findings in patients with Alagille syndrome and end-stage biliary atresia.</p

Clinical profile and laboratory data.

<p>Clinical profile and laboratory data.</p

Hippo-YAP/TAZ signalling coordinates adipose plasticity and energy balance by uncoupling leptin expression from fat mass.

Adipose tissues serve as an energy reservoir and endocrine organ, yet the mechanisms that coordinate these functions remain elusive. Here, we show that the transcriptional coregulators, YAP and TAZ, uncouple fat mass from leptin levels and regulate adipocyte plasticity to maintain metabolic homeostasis. Activating YAP/TAZ signalling in adipocytes by deletion of the upstream regulators Lats1 and Lats2 results in a profound reduction in fat mass by converting mature adipocytes into delipidated progenitor-like cells, but does not cause lipodystrophy-related metabolic dysfunction, due to a paradoxical increase in circulating leptin levels. Mechanistically, we demonstrate that YAP/TAZ-TEAD signalling upregulates leptin expression by directly binding to an upstream enhancer site of the leptin gene. We further show that YAP/TAZ activity is associated with, and functionally required for, leptin regulation during fasting and refeeding. These results suggest that adipocyte Hippo-YAP/TAZ signalling constitutes a nexus for coordinating adipose tissue lipid storage capacity and systemic energy balance through the regulation of adipocyte plasticity and leptin gene transcription