Novel Ultrasonographic Fatty Liver Indicator Can Predict Hepatitis in Children With Non-alcoholic Fatty Liver Disease

Background: Childhood non-alcoholic fatty liver disease (NAFLD) is a public health issue worldwide. To date, liver biopsy remains the gold standard for diagnosing the severity of NAFLD. However, this invasive procedure might contribute to complications. Owing to this reason, a good non-invasive tool to estimate NAFLD in children is urgently needed. We sought to investigate whether a non-invasive semi-quantitative ultrasonographic fatty liver indicator (US-FLI) can estimate NAFLD in children.Methods: Children aged between 10 and 18 years were enrolled prospectively. Abdominal ultrasonography was performed by a single experienced pediatric gastroenterologist and the non-invasive semi-quantitative US-FLI score were used. Patients were diagnosed with NAFLD if they had a US-FLI score ≥2. The anthropometric measures, obesity-related biochemical results, and levels of tumor necrosis factor-α, interleukin-6, caspase-cleaved cytokeratin fragment of cytokeratin 18 (M30), and adiponectin were also checked.Results: Overall, 117 children aged 10–18 years were enrolled. The anthropometric measures and obesity-related biochemical parameters (hsCRP, triglyceride, uric acid, AST, ALT, γ-GT, homeostatic model assessment insulin resistance (HOMA-IR), and M30) were significantly higher in the obesity group than in the non-obesity group (p < 0.05). Similarly, the US-FLI score was significantly higher in the obesity group than that in the non-obesity group (p < 0.001). Multiple linear regression showed that the US-FLI score was significantly associated with the waist-to-height ratio, uric acid, adiponectin, and M30 levels (all p < 0.05) in children with obesity. The US-FLI score ≥6 was the optimal cut-off point for predicting the hepatitis in children with NAFLD. The area under the receiver operating characteristic curve was 0.710 (95% CI: 0.572–0.847; p = 0.005).Conclusions: The non-invasive US-FLI score can predict hepatitis in children with NAFLD without mandatory liver biopsy. Moreover, the waist-to-height ratio, uric acid, adiponectin, and M30 levels were significantly associated with US-FLI score in children with obesity

New genetic loci link adipose and insulin biology to body fat distribution.

Body fat distribution is a heritable trait and a well-established predictor of adverse metabolic outcomes, independent of overall adiposity. To increase our understanding of the genetic basis of body fat distribution and its molecular links to cardiometabolic traits, here we conduct genome-wide association meta-analyses of traits related to waist and hip circumferences in up to 224,459 individuals. We identify 49 loci (33 new) associated with waist-to-hip ratio adjusted for body mass index (BMI), and an additional 19 loci newly associated with related waist and hip circumference measures (P < 5 × 10(-8)). In total, 20 of the 49 waist-to-hip ratio adjusted for BMI loci show significant sexual dimorphism, 19 of which display a stronger effect in women. The identified loci were enriched for genes expressed in adipose tissue and for putative regulatory elements in adipocytes. Pathway analyses implicated adipogenesis, angiogenesis, transcriptional regulation and insulin resistance as processes affecting fat distribution, providing insight into potential pathophysiological mechanisms

Endovascular treatment of a nontraumatic left subclavian artery pseudoaneurysm

Mycotic subclavian artery pseudoaneurysms are rare. There are controversies over the surgical or endovascular approach as the treatment of choice for these lesions. The standard surgical debridement might not be a choice for poorly surgically reachable lesions or for patients with multiple comorbidities. Endovascular aneurysm repair may be an effective alternative in selected cases. This treatment was rarely reported previously. Herein, we present a high-surgical-risk case with a highly suspected left subclavian arterial mycotic pseudoaneurysm, which, although difficult to approach surgically, was successfully managed with stent grafting and a complete antibiotic treatment course. An 89-year-old male was admitted due to intermittent fever and hemoptysis for 2 months. Salmonella group B was cultured from his sputum, and a 3.5 cm pseudoaneurysm was identified by chest multidetector-row computed tomography (MDCT) angiogram. Endovascular treatment with a graft stent was chosen due to high surgical risk and difficult surgical access to the lesion. The intervention was well planned ad hoc, based on MDCT images and meticulously performed by dual endovascular approaches. Antibiotics were continued after the procedure, and the patient was discharged from the hospital. As MDCT disclosed near-complete regression of the pseudoaneurysms 2 months later and the patient was in healthy status, antibiotics were continued for 6 months. He was readmitted 11 months later due to lacunar infarction with minor pneumonia over the left lower lung in which Salmonella enteritis was also diagnosed. After this acute event, he was again hospitalized 14 days later due to sepsis with adult respiratory distress syndrome and shortly expired despite all emergent treatment measures. No evidence of local subclavian infection recurrence was noted throughout or related to subsequent events. In conclusion, endovascular treatment of an infected subclavian artery pseudoaneurysm could be a choice in selected patients, but treatment of underlying infection determines the clinical outcome

The use and clinical outcomes of rotablation in challenging cases in the drug-eluting stent era

Background: Rotational atherectomy (RA) has been advocated in the bare metal stent (BMS) era but is underused now due to technique demands and nonsuperior outcomes. The aim of this study was to evaluate the procedural and clinical outcomes of patients with very complex, severely calcified coronary lesions treated by RA and drug-eluting stents (DESs) in our current percutaneous coronary intervention (PCI) practice in a region where RA use has been limited by lack of insurance reimbursement. Methods: From March 2004 to November 2010, all consecutive patients who required RA treatment for severely calcified de novo lesions of native coronary arteries followed by DES implantation were queried from the cath lab database and recruited. Their clinical and angiographic characteristics at the index PCI were analyzed and completed by a thorough review of the medical charts. Results: A total of 67 consecutive patients with 71 very complex, heavily calcified coronary lesions treated with RA plus DES were recruited. Of these patients, 64% presented with acute coronary syndrome, 9.0% with cardiogenic shock, 43.3% with chronic renal failure, and 50.7% with diabetes. Multiple-vessel diseases were found in 92.5% of our patients, and the average coronary artery calcification (CAC) score was 3.6±1.4. Of the coronary lesions, 26.7% were either balloon-uncrossable or balloon-undilatable. The angiographic success rate was 100% with one non-Q myocardial infarction. Five patients (7.5%) died in hospital, all initially presenting with extensive myocardial infarction and/or cardiogenic shock. The out-of-hospital major adverse cardiac event was 17.9% at the mean follow-up of 23.2 months (range: 5–86), primarily due to high target-lesion revascularization and target-vessel revascularization rates of 10.4% and 10.4%, respectively. Only one (1.5%) probable subacute stent thrombosis was observed in the follow-up. Conclusion: RA with DES implantation in very complex, heavily calcified coronary lesions can achieve very low complication and low out-of-hospital major adverse cardiac event rates even in high-risk patients despite use limited by lack of insurance reimbursement. The study results convince us to sustain and even broaden the use of this novel, but underused, device in the DES era

Short-term Follow-up Results of Drug-eluting Stenting in Premature Coronary Artery Disease Patients with Multiple Atherosclerotic Risk Factors

BackgroundPremature coronary artery disease (CAD) is a special entity with a strong link to familial hypercholesterolemia, family history of premature CAD, or multiple coexistent atherosclerotic risk factors. Drug-eluting stenting (DES), including paclitaxel-eluting stenting (PES) and sirolimus-eluting stenting (SES), has been proven to have a lower restenotic rate. However, to date, few studies have investigated the clinical and angiographic results of DES in premature CAD patients.MethodsBetween February 2004 and October 2005, premature CAD patients, defined as those younger than 50 years ofage, who were treated with DES in our medical center were all retrospectively enrolled. Their baseline clinical characteristics, clinical outcome and angiographic follow-up results were analyzed.ResultsA total of 26 patients (M/F: 23/3) were enrolled, with a mean age of 44 ±6 years (range, 24–50 years). Conventional atherosclerotic risk factors were prevalent in this study group, including diabetes mellitus (35%), hypertension (35%), hyperlipidemia (54%) and smoking (73%). Moreover, there was 1 homozygous and 1 heterozygous familial hypercholesterolemia case in our study group. In terms of angiographic results, there were 40 target lesions in 34 target vessels. Forty DES (39 PES, 1 SES) were implanted with a median stent diameter of 3 mm and median length of 24 mm. The clinical follow-up was counted up to May 2006, with a mean follow-up duration of 540 ±168 days; 11 (42%) patients had a second angiogram during the follow-up period (200 ±98 days after DES). None of the patients had target lesion revascularization (TLR). In addition, there was no difference in TLR or stent thrombosis between patients with or without acute coronary syndrome.ConclusionBased on our single-center experience, DES had good short-term follow-up results for a premature CAD group with diverse and multiple atherosclerotic risk factors

Long-term prognosis of vascular access in hemodialysis patients with systemic lupus erythematosus: a retrospective cohort study

Abstract Patients with systemic lupus erythematosus (SLE) have a higher risk of vascular complications. This retrospective cohort study aimed to analyze the differences in the risk of arteriovenous fistula or graft (AVF/AVG) dysfunction in hemodialysis patients with and without SLE from Taiwan’s National Health Insurance Database over a 10-year period. AVF/AVG dysfunction is defined as the occurrence of the first episode of intervention after vascular access creation. A total of 1366 HD patients with SLE had higher incidence rates of AVF/AVG dysfunction than 4098 non-SLE HD patients in the following 4 periods: (1) after 1 year (incidence rates = 15.21% and 13.01%, respectively; subdistribution hazard ratio (SHR) = 1.16; P = 0.007), (2) 1st-to-10th-year period (15.36% and 13.25%; SHR = 1.16; P = 0.007), (3) 5th-to-10th-year period (11.91% and 8.1%; SHR = 1.42; P = 0.003), and (4) overall period (23.53% and 21.66%; SHR = 1.09; P = 0.027). In conclusion, there were significantly higher incidence rates of AVF/AVG dysfunction in SLE patients during the long-term follow-up period. Vascular access function should be monitored regularly by clinical examinations, especially after 1 year and during 5 to 10 years, to improve AVF/AVG patency and dialysis adequacy in SLE patients undergoing maintenance hemodialysis

SaeR as a Novel Target for Antivirulence Therapy against Staphylococcus aureus

ABSTRACT:Staphylococcus aureus is a major human pathogen responsible for a wide range of clinical infections. SaeRS is one of the two-component systems in S. aureus that modulate multiple virulence factors. Although SaeR is required for S. aureus to develop an infection, inhibitors have not been reported. Using an in vivo knockdown method, we demonstrated that SaeR is targetable for the discovery of antivirulence agent. HR3744 was discovered through a high-throughput screening utilising a GFP-Lux dual reporter system driven by saeP1 promoter. ,. The antivirulence efficacy of HR3744 was tested using Western blot, Quantitative Polymerase Chain Reaction, leucotoxicity, and hemolysis tests. In electrophoresis mobility shift assay, HR3744 inhibited SaeR-DNA probe binding. WaterLOGSY-NMR test showed HR3744 directly interacted with SaeR's DNA-binding domain When saeR was deleted, HR3744 lost its antivirulence property, validating the target specificity. Virtual docking and mutagenesis were used to confirm the target's specificity. When Glu159 was changed to Asn, the bacteria developed resistance to HR3744. A structure-activity relationship study revealed that a molecule with a slight modification did not inhibit SaeR, indicating the selectivity of HR3744. Interestingly, we found that SAV13, an analogue of HR3744, was four-times more potent than the HR3744 and demonstrated identical antivirulence property and target specificity. In a mouse bacteraemia model, both HR3744 and SAV13 exhibited in vivo effectiveness. Collectively, we identified the first SaeR inhibitor, which exhibited in vitro and in vivo antivirulence property, and proved that SaeR could be a novel target for developing antivirulence drugs against S. aureus infections