VEGF neutralization can prevent and normalize arteriovenous malformations in an animal model for hereditary hemorrhagic telangiectasia 2

Arteriovenous malformation (AVM) refers to a vascular anomaly where arteries and veins are directly connected through a complex, tangled web of abnormal AV fistulae without a normal capillary network. Hereditary hemorrhagic telangiectasia (HHT) types 1 and 2 arise from heterozygous mutations in endoglin (ENG) and activin receptor-like kinase 1 (ALK1), respectively. HHT patients possess AVMs in various organs, and telangiectases (small AVMs) along the mucocutaneous surface. Understanding why and how AVMs develop is crucial for developing therapies to inhibit the formation, growth, or maintenance of AVMs in HHT patients. Previously, we have shown that secondary factors such as wounding are required for Alk1-deficient vessels to develop skin AVMs. Here, we present evidences that AVMs establish from nascent arteries and veins rather than from remodeling of a preexistent capillary network in the wound-induced skin AVM model. We also show that VEGF can mimic the wound effect on skin AVM formation, and VEGF-neutralizing antibody can prevent skin AVM formation and ameliorate internal bleeding in Alk1-deficient adult mice. With topical applications at different stages of AVM development, we demonstrate that the VEGF blockade can prevent the formation of AVM and cease the progression of AVM development. Taken together, the presented experimental model is an invaluable system for precise molecular mechanism of action of VEGF blockades as well as for preclinical screening of drug candidates for epistaxis and gastrointestinal bleedings.     

A new Centiloid method for 18F-florbetaben and 18F-flutemetamol PET without conversion to PiB

European Journal of Nuclear Medicine and Molecular Imaging - We developed a new method to directly calculate Centiloid (CL) units of 18F-florbetaben (FBB) and 18F-flutemetamol (FMM) without...     

High prevalence of low bone mass and associated factors in Korean HIV-positive male patients undergoing antiretroviral therapy

Introduction

Low bone mass is prevalent in HIV-positive patients. However, compared to Western countries, less is known about HIV-associated osteopenia in Asian populations.

Methods

We performed a cross-sectional survey in Seoul National University Hospital from December 2011 to May 2012. We measured bone mineral density using central dual energy X-ray absorptiometry, with consent, in male HIV-positive patients, aged 40 years and older. Diagnosis of low bone mass was made using International Society for Clinical Densitometry Z-score criteria in the 40–49 years age group and World Health Organization T-score criteria in the >50-year age group. The data were compared with those of a community-based cohort in Korea.

Results

Eighty-four HIV-positive male patients were included in this study. Median age was 49 (interquartile range [IQR], 45–56) years, and median body mass index (BMI) was 22.6 (IQR, 20.9–24.4). Viral suppression was achieved in 75 (89.3%) patients and median duration of antiretroviral therapy was 71 (IQR, 36–120) months. The overall prevalence of low bone mass was 16.7% in the 40–49 years age group and 54.8% in the>50 years age group. Our cohort had significantly lower bone mass at the femur neck and total hip than HIV-negative Koreans in the 40–49 years age group. Low bone mass was significantly associated with low BMI, and a high level of serum carboxy-terminal collagen crosslinks, but was not associated with antiretroviral regimen or duration of antiretroviral therapy.

Conclusions

Low bone mass is prevalent in Korean HIV-positive males undergoing antiretroviral therapy, and may be associated with increased bone resorption.     

Alcoholic fatty liver disease elevates estimated coronary heart disease risk to levels comparable with those of nonalcoholic fatty liver disease in the Korean population: a cross-sectional study

Background/Aims

A close relationship has been established between nonalcoholic fatty liver disease (NAFLD) and an elevated risk of coronary heart disease (CHD), but little is known about the association between alcoholic fatty liver disease (AFLD) and CHD risk. The aim of this study was to determine whether AFLD is associated with elevated CHD risk.

Methods

We retrospectively enrolled 10,710 subjects out of 11,469 individuals who visited the Konkuk University Health Care Center for a routine health checkup in 2010. AFLD was diagnosed made when the usual amount of alcohol consumption exceeded 210 g/week in males and 140 g/week in females for the previous 2 years and when hepatic steatosis was detected by liver ultrasonography. The 10-year risk for CHD was estimated using the Framingham Risk Score.

Results

Hepatic steatosis was diagnosed in 4,142 of the 10,710 individuals (38.7%); the remainder (i.e., n=6,568) became the control group. The 4,142 individuals with hepatic steatosis were divided into two groups: NAFLD (n=2,953) and AFLD (n=1,189). The risk of CHD was higher in AFLD (6.72±0.12) than in the control group (5.50±0.04, P<0.001), and comparable to that in NAFLD (7.32±0.07, P=0.02).

Conclusions

Individuals with AFLD have an elevated 10-year risk of CHD that is comparable to those with NAFLD. Therefore, AFLD should be considered a significant risk for future CHD, and preventive measures should be considered earlier.     

Prevalence of renal dysfunction in patients with cirrhosis according to ADQI-IAC working party proposal

Background/Aims

A revised classification system for renal dysfunction in patients with cirrhosis was proposed by the Acute Dialysis Quality Initiative and the International Ascites Club Working Group in 2011. The aim of this study was to determine the prevalence of renal dysfunction according to the criteria in this proposal.

Methods

The medical records of cirrhotic patients who were admitted to Konkuk University Hospital between 2006 and 2010 were reviewed retrospectively. The data obtained at first admission were collected. Acute kidney injury (AKI) and chronic kidney disease (CKD) were defined using the proposed diagnostic criteria of kidney dysfunction in cirrhosis.

Results

Six hundred and forty-three patients were admitted, of whom 190 (29.5%), 273 (42.5%), and 180 (28.0%) were Child-Pugh class A, B, and C, respectively. Eighty-three patients (12.9%) were diagnosed with AKI, the most common cause for which was dehydration (30 patients). Three patients had hepatorenal syndrome type 1 and 26 patients had prerenal-type AKI caused by volume deficiency after variceal bleeding. In addition, 22 patients (3.4%) were diagnosed with CKD, 1 patient with hepatorenal syndrome type 2, and 3 patients (0.5%) with AKI on CKD.

Conclusions

Both AKI and CKD are common among hospitalized cirrhotic patients, and often occur simultaneously (16.8%). The most common type of renal dysfunction was AKI (12.9%). Diagnosis of type 2 hepatorenal syndrome remains difficult. A prospective cohort study is warranted to evaluate the clinical course in cirrhotic patients with renal dysfunction.     

A synchronous hepatocellular carcinoma and renal cell carcinoma treated with radio-frequency ablation

Radio-frequency ablation (RFA) is a curative treatment for hepatocellular carcinoma (HCC). Percutaneous RFA has been shown to be beneficial for patients with small renal cell carcinoma (RCC) lacking indications for resection. We experienced the case of a 53-year-old male who had conditions that suggested HCC, RCC, and alcoholic liver cirrhosis. Abdominal contrast-enhanced computed tomography (CT) and magnetic resonance image showed liver cirrhosis with 2.8 cm ill-defined mass in segment 2 of the liver and 1.9 cm hypervascular mass in the left kidney. These findings were compatible with the double primary cancers of HCC and RCC. Transarterial chemoembolization (TACE) was performed to treat the HCC. After the TACE, a focal lipiodol uptake defect was noticed on a follow up CT images and loco-regional treatment was recommended. Therefore, we performed RFAs to treat HCC and RCC. There was no evidence of recurrence in the follow up image after 1 month.     

Impact of Social Distancing on Intussusception Incidence in Children

Following nonpharmaceutical intervention (NPI) to mitigate coronavirus disease 2019 has led to drastic reduction in incidence of communicable disease. Intussusception is commonly preceded by infectious pathogens. Indirect effect from NPI implementation on incidence of intussusception has not been understood fully. We conducted a cohort study to estimate the impact of NPI on incidence of intussusception in Korean children. The net risk ratio of intussusception incidence for 2020 compared to 2010–2019 was 0.53 (95% confidence interval [CI], 0.43–0.64) for boys and 0.56 (95% CI, 0.44–0.71) for girls (P for difference = 0.017). Our study showed an association between NPI implementation and reduction of intussusception incidence, with more profound reduction in boys compared to girls.     

Synthesis,structures, and catalytic efficiency in ring opening polymerization of rac-lactide with tridentate vs. bidentate cobalt(ii), zinc(ii), and cadmium(ii) complexes containing N-substituted N,N-bis((3,5-dimethyl-1H-pyrazol-1-yl)methyl)amine ligands

A series of Co(ii), Zn(ii), and Cd(ii) complexes supported by 1-(3,5-dimethyl-1H-pyrazol-1-yl)-N-((3,5-dimethyl-1H-pyrazol-1-yl)methyl)-N-(furan-2-ylmethyl)methanamine (L_A) and N,N-bis((3,5-dimethyl-1H-pyrazol-1-yl)methyl)-4-isopropylaniline (L_B) were synthesized. The direct chelation of CoCl₂·6H₂O, ZnCl₂, and CdBr₂·4H₂O by the ligands produced [L_nMX₂] (L_n = L_A or L_B; M = Zn or Co, with X = Cl; M = Cd, with X = Br) complexes in high yields. Structural studies revealed that [L_BCoCl₂] and [L_BZnCl₂] adopted distorted tetrahedral geometries, as L_B coordinated the metal centers in a bidentate fashion, while L_A coordinated the metal centers in a tridentate fashion through the nitrogen atoms of the pyrazole and amine moieties, so that [L_ACoCl₂] and [L_AZnCl₂] exhibited trigonal bipyramidal geometries and [L_ACdBr₂] a square pyramidal geometry. [L_BCdBr₂] has two Cd-containing structures per unit cell, whereby one Cd center adopted a distorted tetrahedral geometry and the other exhibited square bipyramidal geometry. The in situ-generated alkyl derivatives of the synthesized complexes were assessed in the ring-opening polymerization of rac-lactide. Heterotactic polylactides (PLAs) were furnished with all complexes. The [L_BZnCl₂]/MeLi system produced PLA with a superior heterotactic bias (P_r up to 0.94) at −25 °C. PLAs with wide-ranging polydispersity indices (1.16–2.23) and low molecular weights were produced in all cases, irrespective of the specific M(II) center and ancillary ligand utilized.

Co(ii), Zn(ii), and Cd(ii) complexes supported by bis-pyrazolyl ligands were applied to the ring-opening polymerization of rac-lactide to produce heterotactic polylactides (PLAs) with superior heterotactic bias i.e. P_r up to 0.94 at −25 °C.