Background/Aims: Patients with liver cirrhosis (LC) have low levels of branchedchain amino acids (BCAAs). There is accumulating evidence that BCAAs have anti- fibrotic effects in cirrhosis. This study is aimed to evaluate the effect of BCAAs on the function and phenotype of activated hepatic stellate cells (HSCs). Methods: LX-2, an immortalized human stellate cell line, was used in in vitro experiments. LX-2 cells were exposed to transforming growth factor β1 (TGF-β1) and BCAAs or to valine, leucine, and isoleucine, which are components of BCAAs. Activation of the TGF-β signaling pathway in LX-2 cells was observed using real- time quantitative polymerase chain reaction and Western blotting. Results: The increased expression of snail family transcriptional repressor 1 (SNAI1) was observed in LX-2 cells activated by TGF-β1. After BCAA treatment, its expression was significantly decreased at the mRNA level. The increased expression of Col1α1 and TIMP2 at the mRNA level and alpha smooth muscle actin at the protein level in activated LX-2 cells decreased after BCAA treatment. Among the BCAA components, leucine and valine significantly abrogated TGF-β-induced activation of LX-2 cells. BCAA treatment led to the decreased phosphorylation of Smad2 and p38 proteins, which are markers for Smad and Smad-independent p38 mitogen-activated protein kinase signaling pathways, respectively. Conclusions BCAA treatment can improve hepatic fibrosis by directly affecting the activated state of hepatic stellate cells through inhibition of the TGF-β signaling pathway. Among BCAA components, leucine and valine mainly abrogated TGF-β-induced activation of HSCs. Our results suggest that BCAA may be used to attenuate the progression of liver fibrosis.

Background: To estimate real-world outcomes in East Asian populations, we conducted a nationwide retrospective analysis of the efficacy and safety of lenalidomide for del(5q) myelodysplastic syndrome (MDS) patients with transfusion-dependent anemia in Korea. Methods: Patients aged ≥19 years who had received lenalidomide for the treatment of lower-risk, red blood cell (RBC) transfusion-dependent del(5q) MDS were selected. A filled case report form (CRF) with information from electronic medical records was requested from members of the acute myeloid leukemia (AML)/MDS Working Party of the Korean Society of Hematology. All the CRFs were gathered and analyzed. Results: A total of 31 patients were included in this study. Of 28 evaluable patients, 19 (67.9%) achieved RBC transfusion independence (RBC-TI). Female sex and the development of thrombocytopenia during treatment were associated with achieving RBC-TI. The most common non-hematologic toxicities were pruritus, fatigue, and rashes. All non-hematologic toxicities of grades ≥3 were limited to rash (12.9%) and pruritus (6.5%). Dose reduction was required in 15 of the 19 responders (78.9%). The most common final stable dosing schedule for the responders was 5 mg once every other day (31.6%). Conclusion Lenalidomide efficacy and tolerability were similar in the Asian del(5q) MDS patients and western patients. Dose reduction during treatment was common, but it was not associated with inferior outcomes.

Background: To estimate real-world outcomes in East Asian populations, we conducted a nationwide retrospective analysis of the efficacy and safety of lenalidomide for del(5q) myelodysplastic syndrome (MDS) patients with transfusion-dependent anemia in Korea. Methods: Patients aged ≥19 years who had received lenalidomide for the treatment of lower-risk, red blood cell (RBC) transfusion-dependent del(5q) MDS were selected. A filled case report form (CRF) with information from electronic medical records was requested from members of the acute myeloid leukemia (AML)/MDS Working Party of the Korean Society of Hematology. All the CRFs were gathered and analyzed. Results: A total of 31 patients were included in this study. Of 28 evaluable patients, 19 (67.9%) achieved RBC transfusion independence (RBC-TI). Female sex and the development of thrombocytopenia during treatment were associated with achieving RBC-TI. The most common non-hematologic toxicities were pruritus, fatigue, and rashes. All non-hematologic toxicities of grades ≥3 were limited to rash (12.9%) and pruritus (6.5%). Dose reduction was required in 15 of the 19 responders (78.9%). The most common final stable dosing schedule for the responders was 5 mg once every other day (31.6%). Conclusion Lenalidomide efficacy and tolerability were similar in the Asian del(5q) MDS patients and western patients. Dose reduction during treatment was common, but it was not associated with inferior outcomes.

Purpose: EGFR-mutation (EGFR-mt) is a major oncogenic driver mutation in lung adenocarcinoma (ADC) and is more oftenobserved in Asian population. In lung ADC, some radiomics parameters of FDG PET have been reported to be associated withEGFR-mt. Here, the associations between EGFR-mt and PET parameters, particularly asphericity (ASP), were evaluated inAsian population. Methods: Lung ADC patients who underwent curative surgical resection as the first treatment were retrospectively enrolled.EGFR mutation was defined as exon 19 deletion and exon 21 point mutation and was evaluated using surgical specimens. OnFDG PET, image parameters of maximal standardized uptake value (SUVmax), metabolic tumor volume (MTV), total lesionglycolysis (TLG), and ASP were obtained. The parameters were compared between EGFR-mt and wild type (EGFR-wt) groups,and the relationships between these PET parameters and EGFR-mt were evaluated. Results: A total of 64 patients (median age 66 years, M:F = 34:30) were included in the analysis, and 29 (45%) patients showedEGFR-mt. In EGFR-mt group, all the image parameters of SUVmax, MTV, TLG, and ASP were significantly lower than inEGFR-wt group (all adjusted P< 0.050). In univariable logistic regression, SUVmax (P= 0.003) and ASP (P= 0.010) weresignificant determinants for EGFR-mt, whereasMTV was not (P= 0.690). Multivariate analysis revealed that SUVmax and ASPare independent determinants for EGFR-mt, regardless of inclusion of MTV in the analysis (P< 0.05). Conclusion In Asian NSCLC/ADC patients, SUVmax, MTV, and ASP on FDG PET are significantly related to EGFR mutationstatus. Particularly, low SUVmax and ASP are independent determinants for EGFR-mt.

Purpose: The precise quantification of dopamine transporter (DAT) density on N-(3-[18F]Fluoropropyl)-2β-carbomethoxy-3β-(4-iodophenyl) nortropane positron emission tomography ([18F]FP-CIT PET) imaging is crucial to measure the degree of striatal DAT loss in patients with parkinsonism. The quantitative analysis requires a spatial normalization process based on a template brain. Since the spatial normalization method based on a delayed-phase PET has limited performance, we suggest an early-phase PET-based method and compared its accuracy, referring to the MRI-based approach as a gold standard. Methods: A total of 39 referred patients from the movement disorder clinic who underwent dual-phase [18F]FP-CIT PET and took MRI within 1 year were retrospectively analyzed. The three spatial normalization methods were applied for quantification of [18F]FP-CIT PET-MRI-based anatomical normalization, PET template-based method based on delayed PET, and that based on early PET. The striatal binding ratios (BRs) were compared, and voxelwise paired t tests were implemented between different methods. Results: The early image-based normalization showed concordant patterns of putaminal [18F]FP-CIT binding with an MRI-based method. The BRs of the putamen from the MRI-based approach showed higher agreement with early image- than delayed image-based method as presented by Bland-Altman plots and intraclass correlation coefficients (early image-based, 0.980; delayed image-based, 0.895). The voxelwise test exhibited a smaller volume of significantly different counts in putamen between brains processed by early image and MRI compared to that between delayed image and MRI. Conclusion The early-phase [18F]FP-CIT PET can be utilized for spatial normalization of delayed PET image when the MRI image is unavailable and presents better performance than the delayed template-based method in quantitation of putaminal binding ratio.

BACKGROUND: Proprotein convertase subtilisin/kexin type 9 (PCSK9) is a circulating protein that promotes degradation of the low density lipoprotein receptor. PCSK9 has emerged as a target for lipid-lowering therapy, but the predictive value of the serum level of PCSK9 for the severity of coronary disease is largely unknown. METHODS: From December 2009 to July 2012, 121 individuals who underwent coronary angiography (CAG) because of clinically suspected acute coronary syndrome were enrolled in this study. Serum levels of PCSK9 and metabolic parameters were measured. SYNTAX (SYNergy between percutaneous coronary intervention with [paclitaxel-eluting] TAXUS stent and cardiac surgery) and GRACE (Global Registry of Acute Coronary Events) scores were calculated. RESULTS: Individuals with CAG lesions (n=100) had significantly higher levels of PCSK9 than those without lesions (n=21). The study population was stratified into three groups according to serum levels of PCSK9. The odds radio for occurrence of one or more CAG lesions was significantly higher in the group with the highest level of PCSK9 (odds ratio, 7.468; P=0.011) than in the group with the lowest level of PCSK9. Serum PCSK9 was positively associated with the number of involved coronary arteries. Multivariable linear regression indicated that levels of PCSK9 were positively correlated with GRACE risk scores and SYNTAX scores. CONCLUSION: Serum PCSK9 concentrations are higher in patients with coronary artery lesions, and are associated with SYNTAX and GRACE scores, suggesting that PCSK9 is a potential biomarker of the severity of coronary artery disease.
Acute Coronary Syndrome* ; Cardiovascular Diseases ; Coronary Angiography ; Coronary Artery Disease ; Coronary Disease ; Coronary Vessels ; Humans ; Linear Models ; Percutaneous Coronary Intervention ; Proprotein Convertases ; Receptors, LDL ; Stents ; Taxus

Respiratory-gated ¹⁸F-fluorodeoxygluocse (¹⁸F-FDG) PET/CT has been successfully used to better localize malignancies in the lung or upper abdominal organs. However, clinical usefulness of respiratory-gated ¹⁸F-FDG PET/CT in detection of fever focus has not been reported yet. A 68-year-old male patient with a history of living donor liver transplantation and biliary stenting was referred for ¹⁸F-FDG PET/CT due to fever of unknown origin (FUO). To find the accurate fever focus, respiratory-gated and non-gated ¹⁸F-FDG PET/CT was performed. Respiratory-gated PET/CT readily revealed prominent hypermetabolic lesion in the distal common bile duct (CBD) area where previous surgical graft was in situ. Maximum standardized uptake value (SUVmax) and SUVratio (SUR) were greater in the gated PET/CT (SUVmax 5.4 and SUR 3.5) than in the non-gated PET/CT (SUVmax 4.6 and SUR 3.0). Fever dramatically subsided after removal of the graft in the CBD. This case report implies that respiratory-gated ¹⁸F-FDG PET/CT can visualize upper abdominal fever focus with better contrast than the conventional non-gated method.
Aged ; Common Bile Duct ; Fever of Unknown Origin ; Fever ; Humans ; Liver Transplantation ; Living Donors ; Lung ; Male ; Methods ; Positron-Emission Tomography ; Positron-Emission Tomography and Computed Tomography ; Respiratory-Gated Imaging Techniques ; Stents ; Transplants

PURPOSE: The purpose of the study was to investigate the usefulness of quantitative salivary single-photon emission computed tomography/computed tomography (SPECT/CT) using Tc-99m pertechnetate in Sjögren's syndrome (SS).METHODS: We retrospectively reviewed quantitative salivary SPECT/CT data from 95 xerostomic patients who were classified as either SS (n = 47, male:female = 0:47, age = 54.60 ± 13.16 y [mean ± SD]) or non-SS (n = 48, male:female = 5:43, age = 54.94 ± 14.04 y) by combination of anti-SSA/Ro antibody, labial salivary gland biopsy, unstimulated whole saliva flow rate, and Schirmer's test. Thyroid cancer patients (n = 43, male:female = 19:24, age = 46.37 ± 12.13 y) before radioactive iodine therapy served as negative controls. Quantitative SPECT/CT was performed pre-stimulatory 20 min and post-stimulatory 40 min after injection of Tc-99m pertechnetate (15 mCi). The %injected dose at 20 min and the %excretion between 20 and 40 min were calculated for parotid and submandibular glands, generating four quantitative parameters: %parotid uptake (%PU), %submandibular uptake (%SU), %parotid excretion (%PE), and %submandibular excretion (%SE). The most useful parameter for SS diagnosis was investigated.RESULTS: The uptake parameters (%PU and %SU) were significantly different among the SS, non-SS, and negative controls (p = 0.005 for %PU and p < 0.001 for %SU, respectively), but the excretion parameters (%PE and %SE) were not (p > 0.05 for both). The%PU and%SU were significantly lower in SS than in the negative controls and non-SS (p < 0.05 for all pair-wise comparisons). Additionally, the %SU was significantly lower in non-SS than in the negative controls (p < 0.05). Receiver-operating characteristic analysis revealed that the %SU had the greatest area-under-the curve of 0.720 (95% confidence interval = 0.618–0.807). Using the optimal cut-off value of %SU ≤ 0.07%, SS was identified with a sensitivity of 70.21% and a specificity of 70.83%.CONCLUSION: Reduced submandibular uptake of Tc-99m pertechnetate at 20 min (%SU) was proved useful for the diagnosis of SS. Quantitative salivary gland SPECT/CT holds promise as an objective imaging modality for assessment of salivary dysfunction and may facilitate accurate classification of SS.
Biopsy ; Classification ; Diagnosis ; Humans ; Iodine ; Retrospective Studies ; Saliva ; Salivary Glands ; Sensitivity and Specificity ; Sodium Pertechnetate Tc 99m ; Submandibular Gland ; Thyroid Neoplasms

Respiratory-gated ¹⁸F-fluorodeoxygluocse (¹⁸F-FDG) PET/CT has been successfully used to better localize malignancies in the lung or upper abdominal organs. However, clinical usefulness of respiratory-gated ¹⁸F-FDG PET/CT in detection of fever focus has not been reported yet. A 68-year-old male patient with a history of living donor liver transplantation and biliary stenting was referred for ¹⁸F-FDG PET/CT due to fever of unknown origin (FUO). To find the accurate fever focus, respiratory-gated and non-gated ¹⁸F-FDG PET/CT was performed. Respiratory-gated PET/CT readily revealed prominent hypermetabolic lesion in the distal common bile duct (CBD) area where previous surgical graft was in situ. Maximum standardized uptake value (SUVmax) and SUVratio (SUR) were greater in the gated PET/CT (SUVmax 5.4 and SUR 3.5) than in the non-gated PET/CT (SUVmax 4.6 and SUR 3.0). Fever dramatically subsided after removal of the graft in the CBD. This case report implies that respiratory-gated ¹⁸F-FDG PET/CT can visualize upper abdominal fever focus with better contrast than the conventional non-gated method.

PURPOSE: The purpose of the study was to investigate the usefulness of quantitative salivary single-photon emission computed tomography/computed tomography (SPECT/CT) using Tc-99m pertechnetate in Sjögren's syndrome (SS). METHODS: We retrospectively reviewed quantitative salivary SPECT/CT data from 95 xerostomic patients who were classified as either SS (n = 47, male:female = 0:47, age = 54.60 ± 13.16 y [mean ± SD]) or non-SS (n = 48, male:female = 5:43, age = 54.94 ± 14.04 y) by combination of anti-SSA/Ro antibody, labial salivary gland biopsy, unstimulated whole saliva flow rate, and Schirmer's test. Thyroid cancer patients (n = 43, male:female = 19:24, age = 46.37 ± 12.13 y) before radioactive iodine therapy served as negative controls. Quantitative SPECT/CT was performed pre-stimulatory 20 min and post-stimulatory 40 min after injection of Tc-99m pertechnetate (15 mCi). The %injected dose at 20 min and the %excretion between 20 and 40 min were calculated for parotid and submandibular glands, generating four quantitative parameters: %parotid uptake (%PU), %submandibular uptake (%SU), %parotid excretion (%PE), and %submandibular excretion (%SE). The most useful parameter for SS diagnosis was investigated. RESULTS: The uptake parameters (%PU and %SU) were significantly different among the SS, non-SS, and negative controls (p = 0.005 for %PU and p < 0.001 for %SU, respectively), but the excretion parameters (%PE and %SE) were not (p > 0.05 for both). The%PU and%SU were significantly lower in SS than in the negative controls and non-SS (p < 0.05 for all pair-wise comparisons). Additionally, the %SU was significantly lower in non-SS than in the negative controls (p < 0.05). Receiver-operating characteristic analysis revealed that the %SU had the greatest area-under-the curve of 0.720 (95% confidence interval = 0.618–0.807). Using the optimal cut-off value of %SU ≤ 0.07%, SS was identified with a sensitivity of 70.21% and a specificity of 70.83%. CONCLUSION Reduced submandibular uptake of Tc-99m pertechnetate at 20 min (%SU) was proved useful for the diagnosis of SS. Quantitative salivary gland SPECT/CT holds promise as an objective imaging modality for assessment of salivary dysfunction and may facilitate accurate classification of SS.