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Microvascular reconstruction is often limited by the availability and length of the pedicle. The harvesting of autologous vein grafts adds morbidity and may not provide a good match. Expanded polytetrafluoroethylene (ePTFE) grafts have been used routinely in macrovascular surgery. However, there are no conclusive data on the performance of small-diameter PTFE grafts for pedicle lengthening in free flaps in a low-pressure situation. In this study, we evaluated the efficacy of 3-mm diameter stretch ePTFE grafts to lengthen the venous pedicle of a free flap. Methods: Fifteen male New Zealand white rabbits were operated on under sterile conditions. Using an operating microscope, an epigastric flap was raised and the pedicle was exposed and dissected to its origin from the superficial femoral vessels. A segment of the vein of 1cm to 3cm was replaced with a stretch ePTFE graft. Microsurgical anastomoses were performed using 9-0 nylon sutures. Four weeks postoperatively, the flaps were raised again with the pedicles re-explored. The graft was then removed and examined histologically. Results: All the grafts demonstrated immediate patency. There were no cases of flap loss on the control side at 4 weeks postoperatively. When re-explored, the patent ePTFE grafts appeared to be covered by connective tissue. Light microscopy showed neoendothelialization with fibrovascular ingrowth. Conclusion: From this study, we can conclude that 3-mm diameter stretch ePTFE grafts can be used successfully as an alternative to bridging autologous vein grafts in free-flap pedicles.

Background & Aims: RG6346 is an N-acetyl-D-galactosamine (GalNAc)-conjugated, double-stranded RNA interference agent targeting the HBV genome S-region. We investigated the safety, tolerability, pharmacokinetics, and pharmacodynamics of RG6346 in healthy volunteers and patients with chronic HBV infection (CHB)., Methods: This first-in-human, adaptive, randomized, double-blinded, phase I study recruited three groups of participants: Group A, 30 healthy volunteers received single-dose RG6346 at 0.1, 1.5, 3.0, 6.0, or 12.0 mg/kg, or placebo; Group B, nucleos(t)ide analogue-naïve participants with CHB received single-dose RG6346 at 3.0 mg/kg (n = 6) or placebo (n = 3); Group C, participants with nucleos(t)ide-suppressed CHB received four doses (every 28 days) of RG6346 at 1.5, 3.0, or 6.0 mg/kg (n = 4 in each cohort) or placebo (n = 6)., Results: RG6346 treatment for up to 4 months was safe and well tolerated. The most common adverse event was a mild injection site reaction. Several nucleos(t)ide-naïve participants exhibited self-resolving transaminase elevations with preserved liver function. By the end of RG6346 treatment in Group C (Day 112), the mean reduction from baseline in hepatitis B surface antigen (HBsAg) was 1.39, 1.80, and 1.64 log 10 IU/ml in the 1.5, 3.0, and 6.0 mg/kg cohorts, respectively. Of the 12 participants in Group C, 11 (91.7%) achieved a ≥1 log 10 IU/ml reduction in HBsAg (3 of 11 [27.3%] had the response sustained at conditional follow-up Day 448). No dose-response relationship was apparent between RG6346 and serum HBsAg levels. The RG6346-induced HBsAg response was independent of hepatitis B e antigen status. Moderate-to-marked sustained reductions of hepatitis B core-related antigen, HBV RNA, HBV DNA (in nucleos[t]ide analogue-naïve participants), and hepatitis B e antigen levels were observed., Conclusions: These favorable safety and pharmacodynamic data support the clinical development of RG6346 as the backbone of a finite antiviral treatment regimen, with the goal of sustained HBsAg loss (functional cure) in patients with CHB., Clinical Trial Number: ClinicalTrials.gov NCT03772249., Impact and Implications: Currently available therapies for chronic HBV infection are associated with low rates of functional cure and new, more efficacious treatments are needed. This first-in-human study of RG6346, an RNA interference therapy, showed a favorable safety profile as well as marked and durable reductions in hepatitis B surface antigen levels. These results support the continued development of RG6346 as the backbone of a finite treatment regimen targeting high functional cure rates and are important for HBV researchers and physicians., (Copyright © 2023 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.)

Background & Aims: RNA interference therapy has been shown to reduce hepatitis B surface antigen (HBsAg) levels in preclinical models, which could confer functional cure in patients with chronic hepatitis B. This phase IIa trial (ClinicalTrials.gov Identifier: NCT03365947) assessed the safety and efficacy of the small-interfering RNA JNJ-73763989 (JNJ-3989) plus a nucleos(t)ide analogue (NA), with/without the capsid assembly modulator JNJ-56136379 (JNJ-6379) in patients with chronic hepatitis B., Methods: Treatment-naïve and NA-suppressed patients received 3 subcutaneous JNJ-3989 doses every week (QW; 100, 200, or 300 mg), 2 weeks (Q2W; 100 mg) or 4 weeks (Q4W; 25, 50, 100, 200, 300, or 400 mg), or JNJ-3989 Q4W (200 mg) plus oral JNJ-6379 250 mg daily for 12 weeks. Patients received NAs throughout., Results: Eighty-four patients were recruited. All treatments were well tolerated, with all 5 serious adverse events considered unrelated to study drugs. JNJ-3989 100 to 400 mg Q4W resulted in HBsAg reductions ≥1 log 10 IU/ml from baseline in 39/40 (97.5%) patients at the nadir. All patients receiving the triple combination (n = 12) had HBsAg reductions ≥1 log 10 IU/ml from baseline at the nadir. HBsAg reductions were similar for HBeAg-positive (n = 21) and HBeAg-negative (n = 47) patients in all JNJ-3989 Q4W treatment arms, including the triple combination (n = 68). Smaller HBsAg reductions were seen with 25 mg (n = 8) and 50 mg (n = 8) than with 100 to 400 mg (n = 40). Shorter dosing intervals (QW [n = 12] and Q2W [n = 4]) did not improve response vs. Q4W dosing. HBsAg reductions ≥1 log 10 IU/ml from baseline persisted in 38% of patients 336 days after the last JNJ-3989 dose., Conclusions: JNJ-3989 plus an NA, with/without JNJ-6379, was well tolerated and resulted in HBsAg reductions up to 336 days after the last JNJ-3989 Q4W dose., Clinical Trial Number: NCT03365947., Lay Summary: Hepatitis B virus affects people's livers and produces particles called hepatitis B surface antigen (HBsAg) that damage a person's liver and can help the virus infect a person for a long time, known as chronic hepatitis B (CHB). In this study, a new treatment called JNJ-3989 was assessed (in combination with normal treatment known as nucleos(t)ide analogues), for its safety and effectiveness in reducing the number of HBsAg particles in people with CHB. The results of this study showed that treatment with JNJ-3989 could be safe for people with CHB, lowered their HBsAg levels, and kept HBsAg levels lowered for 336 days in 38% of patients after receiving their last dose of JNJ-3989., Competing Interests: Conflicts of interest MFY serves as advisor/consultant for AbbVie, Arbutus Biopharma, Allovir International, Aligos Therapeutics, Clear B Therapeutics, Dicerna Pharmaceuticals, Finch Therapeutics, GlaxoSmithKline, Gilead Sciences, Janssen, Merck Sharp and Dohme, and Roche and received grant/research support from Assembly Biosciences, Arrowhead Pharmaceuticals, Dicerna Pharmaceuticals, Gilead Sciences, Merck Sharp and Dohme, Roche, and Vir Biotechnology. SS received honoraria for advisory boards or speaker fees from AbbVie, AstraZeneca, Bayer, BMS, Chiesi, CSL Behring, Dr Falk, Eisai, Gilead, Ipsen, MSD, Pfizer, and Roche Products. WS received payments from Janssen for providing a clinical site for the current study. AJT served on advisory boards for Janssen, Gilead, AbbVie, Merck, BMS, Roche, Bayer, Eisai, Roche Diagnostics, and Assembly Biosciences; received speaker fees from Gilead, AbbVie, Merck, Roche, and BMS; received institutional research grants from NHMRC/MRFF, Gilead Sciences, and Roche Diagnostics; and serves as a board member and director of the Gastroenterological Society of Australia. BG, TS, and JH are current or former employees of Arrowhead and may be Arrowhead shareholders. MB, RK, MB, OL, and FDR are current or former employees of Janssen Pharmaceuticals and may be Johnson & Johnson stockholders. GC is an Abbott employee and shareholder. KJ receives funding from SpringBank Pharmaceuticals. CLL discloses sponsored lectures for Gilead Sciences. RGG is/has been a consultant and/or advisor to Abbot, AbbVie, Access Biologicals, Alexion, Antios, Arrowhead, Bayer AG, Bristol Myers Squibb, Eiger, Eisai, Enyo, eStudySite, Forty-Seven Inc, Gilead Sciences, HepaTX, HepQuant, Intercept, Ionis Pharmaceuticals, Janssen, Laboratory for Advanced Medicine, Lilly, Merck, Salix, Shionogi, and Trimaran and Viking Therapeutics; provides consulting for ADMA Biologics, AEC Partners, Arena Pharmaceuticals Inc, Arterys Inc, Cirina, Consumer Health Products Assoc, DRG Abacus, Intellia, Iqvia, KannaLife, Labyrinth Holdings, Organovo, Patient Connect and Spring Bank; is on scientific or clinical advisory boards for Abbott, AbbVie, Merck, Arrowhead, Bayer, Dova Pharmaceuticals, Eiger, Enyo, Hatch Biofund, HepQuant, Intercept, Janssen, and Medimmune; is an advisory consultant for Biocollections, Fujifilm/Wako, and Quest; is chair of the clinical advisory board for Prodigy, is on the data safety monitoring board for Altimmune, Arrowhead, CymaBay Therapeutics, and Durect; has speaker contracts with AbbVie, Bayer, Bristol Myers Squibb, Dova Pharmaceuticals, Eisai, Genentech, Gilead, Intercept, Salix, and Shionogi; is a minor stock shareholder in Athenex, Cocrystal, RiboSciences, and Triact; and holds stock options in Athenex, Eiger, HepaTx, and HepQuant; over 80% of income from Pharma received by RGG is directed to research, education, public policy, and/or donated to charities. EG has been an advisor and/or speaker for AbbVie, Arrowhead, Assembly, Gilead, GSK, Janssen, Merck, Novartis, Roche, and Vir Biotechnology. SL, THL, WC, CS, and DKHW have no disclosures to report. Please refer to the accompanying ICMJE disclosure forms for further details., (Copyright © 2022 The Author(s). Published by Elsevier B.V. All rights reserved.)

We report herein the design and synthesis of colloidally-stable S/Ag 1.93 S nanoparticles, their photothermal conversion properties and in vitro cytotoxicity toward A431 skin cancer cells under the excitation of a minimally-invasive 980 nm near-infrared (NIR) laser. Micron-sized S particles were first synthesized via acidifying Na 2 S 2 O 3 using biocompatible sodium alginate as a surfactant. In the presence of AgNO 3 and under rapid microwave-induced heating, alginate reduced AgNO 3 to nascent Ag which reacted with molten S in situ forming S/Ag 1.93 S nanoparticles. The nanoparticles were characterized using a combination of X-ray diffraction, electron microscopies, elemental analysis, zeta-potential analysis and UV-VIS-NIR spectroscopy. The average particles size was controlled between 40 and 60 nm by fixing the mole ratio of Ag + :S 2 O 3 2- . When excited by a 980 nm laser, S/Ag 1.93 S nanoparticles (~40 nm) produced with the least amount of AgNO 3 exhibited a respectable photothermal conversion efficiency of circa 62% with the test aqueous solution heated to a hyperthermia-inducing 52 °C in 15 min. At 0.7 W/cm 2 , the viability of A431 skin cancer cells incubated with 7.0 ± 0.2 μg/mL of S/Ag 1.93 S nanoparticles reduced to 14 ± 0.6%, while an A431 cell control maintained an 80% cell viability. These results suggested that S/Ag 1.93 S nanoparticles may have good potential in reducing metastatic skin carcinoma., (Copyright © 2022 Elsevier B.V. All rights reserved.)

The detection of chromosomal abnormalities is important in the diagnosis, prognosis and disease monitoring in plasma cell neoplasia (PCN). However, the gold standard diagnostic techniques of conventional cytogenetics (CC) and fluorescence in situ hybridization (FISH) are hampered by culture difficulties and probe availability. Cytogenomic microarray (CMA), however, is able to surmount such limitations and generate a comprehensive genomic profile with the implementation of plasma cell (PC) enrichment. In this study, we examined 89 bone marrow specimens with CC and FISH without PC enrichment, 35 of which were examined with CMA after PC enrichment. Results revealed that after PC enrichment, CMA was able to detect chromosomal abnormalities in 34 of 35 specimens tested (97.1%), compared to 21 and 32 specimens (60% and 91.4%, respectively) achieved by CC and FISH, respectively, which were similar to the abnormality detection rates among all 89 specimens (59.5% by CC and 92.1% by FISH). In addition, as the only technique capable of detecting copy neutral loss of heterozygosity (CN-LOH) and chromothripsis, CMA appears to be the most powerful tool in risk stratification as it successfully re-stratified 9 (25.7%) and 12 (34.3%) specimens from standard risk (determined by CC and FISH, respectively) to high risk. Based on the encouraging data presented by our study and others, we conclude that implementation of CMA with PC enrichment is of great value in routine clinical workup in achieving a more complete genetic profile of patients with PCN., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Introduction: RET rearrangements are an emerging targetable oncogenic fusion driver in NSCLC. However, the natural history of disease and activity of different classes of systemic therapy remain to be defined. Furthermore, molecular testing for RET is not yet routine, and the optimal method of testing is unclear. We present a comparative analysis of molecular profiling with fluorescence in situ hybridization (FISH) or next-generation sequencing (NGS) and treatment outcomes., Methods: This study was a retrospective analysis of patients treated at the National Cancer Centre Singapore. Baseline demographics and treatment outcomes were collected., Results: A total of 64 patients were included, with a median age of 62 years (range: 25-85), 56% were women, 77% were of Chinese ethnicity, 95% had adenocarcinoma, and 69% were never smokers. RET rearrangement was detected by FISH in 30 of 34 patients (88%), NGS in 40 of 43 patients (93%), and with discordant results in seven of 13 patients (54%) tested with both methods. Of 61 patients with stage IIIB/IV or recurrent disease, prevalence of central nervous system metastases was 31% and 92% received palliative systemic therapy. Overall survival was prolonged in patients treated with a selective RET tyrosine kinase inhibitor versus untreated patients (median 49.3 versus 15.3 mo; hazard ratio [HR]: 0.16, 95% confidence interval [CI]: 0.06-0.40, p < 0.001). However, it was not different in patients treated with immunotherapy versus untreated patients (median 37.7 versus 49.3 mo; HR: 1.30, 95% CI: 0.53-3.19, p = 0.53). Overall survival was also prolonged in patients with CCDC6-RET fusion versus those with KIF5B-RET fusion (median 113.5 versus 37.7 mo; HR: 0.12, 95% CI: 0.04-0.38, p = 0.009)., Conclusions: In RET-rearranged NSCLC, selective RET tyrosine kinase inhibitor therapy is associated with improved survival outcomes, especially in patients with CCDC6-RET fusion. However, immunotherapy has poor efficacy. NGS and FISH testing methods may also result in substantial discordance., (Copyright © 2020. Published by Elsevier Inc.)

Sago pith cellulose nanofibril (SPCNF) aerogel derived from sago pith waste (SPW) was successfully produced through three consecutive steps, namely dewaxing and delignification, ultra-sonication and homogenization and freeze drying. The aerogel was characterized using field emission scanning electron microscopy (FE-SEM), Fourier-transform infra-red spectroscopy (FTIR), X-ray diffraction (XRD) and thermogravimetric analysis (TGA). Results of the analyses collectively showed that lignin & hemicellulose were absent in the SPCNF aerogel product which has a high crystallinity index of 88%. The diameters of individual nanofibril constituents of the SPCNF were between 15 and 30 nm and aspect ratios >1000 were observed. The SPCNF aerogel, with a density measured at 2.1 mg/cm 3 , was efficient in methylene blue (MB) removal with a maximum MB adsorption of 222.2 mg/g at 20 °C. The adsorption of MB onto the SPCNF aerogel was rapid and found to follow a pseudo-second-order kinetic model with the adsorption isotherm being in congruence with the Langmuir model. The SPCNF aerogel exhibited outstanding MB removal efficacies with 5 mg and 20 mg of SPCNF capable of removing over 90% and almost 99% MB, respectively. The optimized pH value and temperature for MB adsorption were determined as pH 7 and 20 °C., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Background: There are limited data regarding the relation between serum phosphorus concentration (SPC) and subclinical coronary atherosclerosis in the asymptomatic healthy population without kidney dysfunction., Objectives: We aimed to investigate the relation between SPC and characteristics of atherosclerotic plaques and cardiac events according to SPCs using a large cohort of asymptomatic Korean individuals., Methods: We evaluated 6329 asymptomatic Korean individuals [mean age: 53.6 ± 7.6 y, 4611 men (72.9%)] without kidney dysfunction and coronary artery disease who voluntarily underwent coronary computed tomography angiography (CCTA) as part of a general health examination. Study participants were stratified into quartiles according to their SPCs (≤3.0, 3.1-3.3, 3.4-3.7, ≥3.8 mg/dL). The degree and extent of subclinical coronary atherosclerosis were evaluated with CCTA. Stenosis of diameter ≥50% was defined as significant. A cardiac event was defined as a composite of all-cause death, myocardial infarction, unstable angina, and coronary revascularization., Results: After adjustment for cardiovascular disease risk factors, the risk of any atherosclerotic plaque was significantly higher with increasing SPC quartiles (P = 0.001). In particular, the risk of calcified plaque increased in the second (OR: 1.27; 95% CI: 1.07, 1.51; P = 0.006), third (OR: 1.39; 95% CI: 1.17, 1.64; P < 0.001), and fourth SPC quartiles (OR: 1.50; 95% CI: 1.24, 1.82; P < 0.001) compared with that in the first quartile. However, there were no significant differences in the adjusted ORs for noncalcified plaque, mixed plaque, or significant stenosis. During a follow-up of median 5.4 y, there was no significant difference in cardiac events between the SPC quartiles., Conclusions: In asymptomatic Korean individuals without kidney dysfunction, a high SPC was an independent predictor of calcified plaques without any difference in cardiac events. Further long-term prospective studies are required to validate these results., (Copyright © The Author(s) on behalf of the American Society for Nutrition 2020.)

Purpose: To describe the defining features of incomplete retinal pigment epithelium (RPE) and outer retinal atrophy (iRORA), a consensus term referring to the OCT-based anatomic changes often identified before the development of complete RPE and outer retinal atrophy (cRORA) in age-related macular degeneration (AMD). We provide descriptive OCT and histologic examples of disease progression., Design: Consensus meeting., Participants: Panel of retina specialists, including retinal imaging experts, reading center leaders, and retinal histologists., Methods: As part of the Classification of Atrophy Meeting (CAM) program, an international group of experts analyzed and discussed longitudinal multimodal imaging of eyes with AMD. Consensus was reached on a classification system for OCT-based structural alterations that occurred before the development of atrophy secondary to AMD. New terms of iRORA and cRORA were defined. This report describes in detail the CAM consensus on iRORA., Main Outcome Measures: Defining the term iRORA through OCT imaging and longitudinal cases showing progression of atrophy, with histologic correlates., Results: OCT was used in cases of early and intermediate AMD as the base imaging method to identify cases of iRORA. In the context of drusen, iRORA is defined on OCT as (1) a region of signal hypertransmission into the choroid, (2) a corresponding zone of attenuation or disruption of the RPE, and (3) evidence of overlying photoreceptor degeneration. The term iRORA should not be used when there is an RPE tear. Longitudinal studies confirmed the concept of progression from iRORA to cRORA., Conclusions: An international consensus classification for OCT-defined anatomic features of iRORA are described and examples of longitudinal progression to cRORA are provided. The ability to identify these OCT changes reproducibly is essential to understand better the natural history of the disease, to identify high-risk signs of progression, and to study early interventions. Longitudinal data are required to quantify the implied risk of vision loss associated with these terms. The CAM classification provides initial definitions to enable these future endeavors, acknowledging that the classification will be refined as new data are generated., (Copyright © 2019 American Academy of Ophthalmology. All rights reserved.)

Background and Aims: There are limited data on the association between serum uric acid (SUA) level and subclinical coronary atherosclerosis. This study investigated the influence of SUA level on subclinical coronary atherosclerosis, as detected by coronary computed tomography angiography (CCTA), in an asymptomatic population., Methods: We evaluated 6431 asymptomatic individuals (mean age 53.6 ± 7.6 years, 4691 men [72.9%]) with no prior history of coronary artery disease, who voluntarily underwent laboratory tests and CCTA as part of a general health examination. The participants were stratified into quartiles according to their SUA levels. Coronary atherosclerotic plaques (calcified, mixed, and non-calcified plaques) were assessed using CCTA. Logistic regression analysis was used to determine the association between SUA levels and subclinical coronary atherosclerosis., Results: The prevalence of any atherosclerotic, calcified, mixed, and non-calcified plaques increased with SUA quartiles (all p < 0.001). After adjustment for cardiovascular risk factors, there were no statistically significant differences in the adjusted odds ratios for calcified plaque (1.19; 95% CI 0.98-1.46; p = 0.080) and mixed plaque (1.25; 95% CI 0.94-1.67; p = 0.132) in the fourth SUA quartile compared to the first quartile. However, the adjusted odds ratios for any atherosclerotic plaque (1.39; 95% CI 1.16-1.68; p < 0.001) and non-calcified plaque (1.38; 95% CI 1.11-1.72; p = 0.004) were significantly higher in the fourth SUA quartile., Conclusions: In asymptomatic individuals, high SUA level was an independent predictor of non-calcified plaques, suggesting an increased cardiovascular risk., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Objectives: This study examined the incremental value of subtended myocardial mass (V sub ) as assessed by coronary computed tomography angiography (CTA) for identifying lesion-specific ischemia verified by invasive fractional flow reserve (FFR) in quantitative coronary CTA., Background: FFR is determined not only by coronary stenosis severity, but also by V sub . One-step evaluation of combined V sub and coronary lesion morphology may improve the accuracy of coronary CTA for identifying ischemia-producing lesions., Methods: A total of 246 intermediate coronary artery lesions (30% to 80% diameter stenosis) in 220 patients (mean age 61.7 years, 168 men) interrogated by FFR were retrospectively studied. Coronary CTA data were used to assess the V sub by coronary artery stenosis, minimal lumen area (MLA), percentage of aggregated plaque volume (%APV), positive remodeling, and low-attenuation plaque. The ability of V sub /MLA 2 to discriminate lesions with FFR ≤0.80 was examined. Diagnostic performance, odds ratios, and category-less net reclassification improvements of coronary CTA parameters for FFR-verified (≤0.80) ischemia were evaluated. On-site computed tomography (CT) derived-FFR (CT-FFR) and quantitative coronary angiography (QCA) data were also compared., Results: Of 246 lesions, 84 (34.1%) showed an FFR ≤0.80. V sub was independently associated with an FFR ≤0.80 (odds ratio: 1.04/1 cm 3 ; p = 0.032) and showed incremental value over MLA. V sub /MLA 2 >4.16 was the best single parameter for discriminating an FFR ≤0.80 with 83.3% sensitivity and 67.9% specificity. The area under the curve (AUC) of V sub /MLA 2 >4.16 (0.80 [95% confidence interval: 0.75 to 0.85]) was better than that of MLA (change in [Δ]AUC: 0.069; p < 0.001), %APV (ΔAUC: 0.096; p = 0.017), and diameter stenosis of QCA (ΔAUC: 0.080; p = 0.037) and was comparable to that of CT-FFR (AUC 0.77; ΔAUC: 0.035; p = 0.304)., Conclusions: V sub is an independent determinant of an FFR ≤0.80. The mathematical index of V sub /MLA 2 >4.16 assessed by coronary CTA shows better diagnostic performance for the detection of ischemia-producing lesions than CT-derived MLA alone or %APV and QCA parameters and was comparable to that of on-site CT-FFR., (Copyright © 2019 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Background & Aims: There are limited data on the association between non-alcoholic fatty liver disease (NAFLD) and subclinical coronary atherosclerosis. This study investigated the influence of NAFLD on subclinical coronary atherosclerosis as detected by coronary computed tomography angiography (CCTA) in an asymptomatic population., Methods: A total of 5,121 consecutive asymptomatic individuals with no prior history of coronary artery disease or significant alcohol intake voluntarily underwent abdominal ultrasonography and CCTA as part of a general health examination. Fatty liver was assessed by ultrasonography examination. The fatty liver index and NAFLD fibrosis score were also calculated. Coronary atherosclerotic plaques on CCTA were evaluated. The association between NAFLD and subclinical coronary atherosclerosis was determined by logistic regression analysis., Results: Of the study participants, 1,979 (38.6%) had ultrasonography-diagnosed NAFLD. After adjustment for cardiovascular risk factors, there were no statistically significant differences in the adjusted odds ratios of NAFLD for calcified plaque (1.03; 95% CI 0.89-1.20; p = 0.673) and mixed plaque (1.15; 95% CI 0.93-1.42; p = 0.214). However, adjusted odds ratios for any atherosclerotic plaque (1.18; 95% CI 1.03-1.35; p = 0.016) and non-calcified plaque (1.27; 95% CI 1.08-1.48; p = 0.003) were significantly higher in NAFLD. In addition, there was a significant association of fatty liver index ≥30 with non-calcified plaque (1.37; 95% CI 1.14-1.65; p = 0.001) and NAFLD fibrosis score ≥-1.455 with non-calcified plaque (1.20; 95% CI 1.08-1.42; p = 0.030)., Conclusions: In this large cross-sectional study of asymptomatic individuals undergoing CCTA, NAFLD was consistently associated with non-calcified plaque, suggesting an increased cardiovascular risk., Lay Summary: In asymptomatic individuals, non-alcoholic fatty liver disease (NAFLD) was an independent risk factor for non-calcified plaque, which has been known as a vulnerable plaque associated with sudden and unexpected cardiac events. Therefore, appropriate medical therapy for NAFLD was required to reduce future cardiac events., (Copyright © 2017 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.)

Background: There are limited data regarding the influence of glycemic status on the risk of subclinical coronary atherosclerosis on coronary computed tomographic angiography (CCTA) in asymptomatic individuals., Methods: We analyzed 6434 asymptomatic individuals who underwent CCTA. The degree and extent of subclinical coronary atherosclerosis were assessed by CCTA, and ≥50% diameter stenosis was defined as significant. Of study participants, 2197 (34.1%), 3122 (48.5%), and 1115 (17.3%) were categorized as normal, prediabetic and diabetic individuals, respectively., Results: Compared with normal individuals, there were no statistically differences in the adjusted odds ratios of prediabetic individuals for significant coronary artery stenosis (0.98, 95% confidence interval [CI] 0.80-1.22, p=0.888), any plaque (0.96, 95% CI 0.86-1.07, p=0.483), calcified plaque (0.90, 95% CI 0.79-1.01, p=0.080), non-calcified plaque (1.02, 95% CI 0.88-1.17, p=0.803), and mixed plaque (1.00, 95% CI 0.82-1.22, p=0.983). However, adjusted odds ratios for significant coronary artery stenosis (1.71, 95% CI 1.34-2.19, p<0.001), any plaque (1.45, 95% CI 1.26-1.68, p<0.001), calcified plaque (1.35, 95% CI 1.15-1.57, p<0.001), non-calcified plaque (1.33, 95% CI 1.11-1.59, p=0.002), and mixed plaque (1.64, 95% CI 1.30-2.07, p<0.001) of diabetic individuals were significantly higher than those of the normal individuals., Conclusion: In asymptomatic individuals, diabetic individuals had a higher risk for subclinical coronary atherosclerosis, but prediabetic individuals were not associated with an increased risk of subclinical coronary atherosclerosis., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Objectives: This study sought to evaluate the long-term prognostic value of coronary computed tomography angiography (CTA) in asymptomatic patients with type 2 diabetes mellitus., Background: There are limited data on the long-term prognostic impact of coronary CTA in asymptomatic patients with type 2 diabetes mellitus., Methods: This study analyzed clinical outcomes of 591 consecutive asymptomatic patients with type 2 diabetes mellitus who underwent coronary CTA (mean age 62.2 ± 8.3 years and 352 men [59.6%]). A cardiac event was defined as a composite of cardiac death, nonfatal myocardial infarction, unstable angina requiring hospitalization, or late coronary revascularization. Patients were categorized into 3 groups according to severity of coronary artery disease (CAD) on coronary CTA: normal coronary arteries, nonobstructive CAD (<50%), and obstructive CAD (≥50%)., Results: One hundred sixty-eight patients (28.4%) had normal coronary arteries, whereas 236 (39.9%) patients had nonobstructive CAD and 187 (31.6%) had obstructive CAD. During the follow-up period (median 5.3 years [interquartile range: 4.7 to 5.8 years]), 37 cardiac events occurred in 29 patents: 10 cardiac deaths, 2 nonfatal myocardial infarctions, 8 cases of unstable angina, and 17 late coronary revascularizations. The 6-year event-free survival rates were 99.3 ± 0.7% in patients with normal coronary arteries, 96.7 ± 1.2% in patients with nonobstructive CAD, and 86.2 ± 3.0% in patients with obstructive CAD (log-rank p < 0.001)., Conclusions: Asymptomatic patients with type 2 diabetes mellitus with normal coronary arteries or nonobstructive CAD on coronary CTA show excellent clinical outcomes over a follow-up period of more than 5 years, whereas prognosis is worse in patients with obstructive CAD. These findings suggest long-term prognostic value of coronary CTA for asymptomatic type 2 diabetes mellitus., (Copyright © 2016 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

A 69-year-old female underwent cardiac CT to evaluate prosthetic valve (PHV) dysfunction detected on echocardiography. A CT coronal and en face views of the mitral annular plane showed a low-density, mass-like lesion on the left atrial side of the PHV and a high-density, plate-like lesion on the left ventricular side of PHV. A repeat of the mitral valve replacement was performed, and preoperative CT findings of both the thrombus on the left atrial side and pannus formation on the LV side were confirmed in the operative findings., (Copyright © 2016 Society of Cardiovascular Computed Tomography. Published by Elsevier Inc. All rights reserved.)

Background: Coronary computed tomographic angiography (coronary CT) is a non-invasive test for diagnosis of cardiac function. Coronary calcium scores determined by coronary CT are associated with cardiovascular risk factors. However, no studies have investigated the association between coronary calcium scores and cardiovascular complications after liver transplantation (LT). We therefore evaluated the utility of preoperative coronary calcium scores for predicting early postoperative cardiovascular complications in LT recipients., Methods: Between 2010 and 2012, 443 LT recipients were analysed retrospectively. Preoperative cardiovascular assessments, including coronary CT, were performed. A coronary calcium score >400 was defined as a positive finding. Predictive factors of early postoperative cardiovascular complications were evaluated by univariate and multivariate analyses. Major cardiovascular complications occurring during a period of 1 month after LT were noted., Results: Of the 443 patients, 38 (8.6%) experienced one or more cardiovascular complications. Positive coronary CT findings were seen in 11 (2.5%) patients. In the multivariate analysis, a coronary calcium score >400 {odds ratio (OR)=4.62 [95% confidence interval (CI): 1.14-18.72], P=0.032} and female sex [OR=2.76 (1.37-5.57), P=0.005] were predictive of cardiovascular complications., Conclusions: A preoperative coronary calcium score of >400 predicted cardiovascular complications occurring 1 month after LT, suggesting that preoperative evaluation of coronary calcium scores could help predict early postoperative cardiovascular complications in LT recipients., (© The Author 2014. Published by Oxford University Press on behalf of the British Journal of Anaesthesia. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)

A 24-year-old man presented to our hospital with symptoms of dyspnea and palpitation for 2 weeks. Cardiac CT showed not only a leaflet coaptation defect in the aortic valve but also a small ventricular septal defect (VSD) immediately beneath the prolapsed right coronary cusp. A shunt flow in the direction of the right ventricular outflow tract though the defect indicated the doubly committed juxta-arterial type of VSD. A doubly committed juxta-arterial VSD of 3 mm was confirmed and repaired via pulmonary arteriotomy., (Copyright © 2014 Society of Cardiovascular Computed Tomography. Published by Elsevier Inc. All rights reserved.)

Individual polar sorbents with surface-displayed amino groups (APS) and non-nucleophilic urea-groups (UPS), were prepared by chemical modification of granular silica gel with bifunctional silane coupling reagents. In this preliminary study, they were separately employed for micro-solid phase extraction (μ-SPE) of the quarternary salt of Amitriptyline (Ami), Carbamazepine (Cbz), Ketoprofen (Ket) and Diclofenac (Dfn) from aqueous samples in conjunction with high performance liquid chromatography. The resulting enrichment factors for both APS and UPS are comparable and exceeded those of μ-SPE involving commercial C18-silica gel sorbents. The presence of highly polar, but non-basic and non-nucleophilic surfaces on UPS prompted the development of a UPS-based μ-SPE method. Good linear correlation was found over a concentration range of 0-50 μg L(-1) with limits of detection ranging from 0.66 to 2.36 μg L(-1)). Limits of quantification between 1.61 and 7.88 μg L(-1) were obtained. HPLC analyses indicated that relative recoveries of 123% for Ami, 65.6% for Cbz, 71.2% for Ket and 66.5% for Dfn were obtained during μ-SPE of spiked (10 μg L(-1)) environmental water samples with percentage relative standard deviations (%RSD) of between 2.1% and 12.6%., (Copyright © 2013 Elsevier B.V. All rights reserved.)

Objective: Aneurysmal subarachnoid hemorrhage (SAH) is a well-known cause of sudden cardio-pulmonary arrest (CPA). Even after successful cardio-pulmonary resuscitation (CPR), the prognosis of patients following an aneurysmal SAH presenting with CPA remains dismal. However, there have been anecdotal reports of good outcomes with appropriate interventions. Pseudo-SAH resulting from marked elevation of intracranial pressure (ICP) after CPR, can mimic SAH in head computed tomographic (CT) scan. Such manifestations hamper resuscitation or delay appropriate neurosurgical management. This study assessed incidence and clinical characteristics of SAH-CPR or pseudo-SAH-CPR patients among non-traumatic CPA-CPR patients, and investigated their therapeutic and prognostic implication., Methods: During the 5-year observation period, 63 non-traumatic coma patients with CT evidence of high attenuation areas in the basal cistern who suffered arrest and underwent CPR during initial resuscitation in the emergency room, were reviewed retrospectively. They were divided into two groups according to the imaging pattern: true-SAH vs. pseudo-SAH, and then true-SAH group were further divided into two groups according to the CT acquisition time: brain CT before arrest vs. brain CT after arrest. Demographic, clinical, and CT data were assessed, and the primary outcome was measured using the 30-day Glasgow Outcome Scale (GOS) score, and the final outcome was evaluated at the end of 3 months post-ictus., Results: When compared with pseudo-SAH (n=28) patients, true-SAH (n=35) patients showed a higher Hounsfield unit values in the affected area, earlier CT acquisition time before CPR, more survivors beyond 3 months (all p<0.05); however, the 30-day survival rate was not significantly different. Of the true-SAH patients, ruptured intracranial aneurysms were found in eight patients, and definite intervention was administered in four patients. When SAH patients were categorized according to the temporal relationship with CPR, the group of 24 patients undergoing CT scan before CPR showed a lower frequency of intraventricular hemorrhage, but showed a higher chance of surgical treatment and survival at 30 days and 3 months compared to the group undergoing CT scan after CPR., Conclusion: The overall survival between true-SAH and pseudo-SAH group was different significantly. Administering definite treatment for a ruptured aneurysm in instances of true SAH could save patients, albeit infrequently. A Prompt CT scan could guarantee recognition of high-density area, blood in the ventricle, and subsequent identification of the ruptured aneurysm, altogether preventing re-bleeding and warranting further systemic resuscitation., (Copyright © 2013 Elsevier B.V. All rights reserved.)

Objectives: We sought to define the clinical importance of an integrated classification of bicuspid aortic valve (BAV) phenotypes and aortopathy using multidetector computed tomography (MDCT)., Background: An association between BAV phenotypes and the pattern of valvular dysfunction or bicuspid aortopathy has yet to be definitely established., Methods: The study cohort included 167 subjects (116 men, age 54.6 ± 14.4 years) who underwent both MDCT and transthoracic echocardiography from 2003 to 2010. Two BAV phenotypes-fusion of the right and left coronary cusps (BAV-AP) and fusion of the right or left coronary cusp and noncoronary cusp (BAV-RL)-were identified. Forty-five patients showed normal aortic dimensions and were classified as type 0. In the remaining patients, hierarchic cluster analysis showed 3 different types of bicuspid aortopathy according to the pattern of aortic dilation: type 1 (aortic enlargement confined to the sinus of Valsalva [n = 34]), type 2 (aortic enlargement involving the tubular portion of the ascending aorta [n = 49]), and type 3 (aortic enlargement extending to the transverse aortic arch [n = 39])., Results: The prevalence of BAV-AP and BAV-RL was 55.7% and 44.3%, respectively. Comparing BAV-AP and BAV-RL, no differences in age or in the prevalence of male sex were determined. However, significant differences in the valvular dysfunction pattern were noted, with moderate-to-severe aortic stenosis predominating in patients with BAV-RL (66.2% vs. 46.2% in BAV-AP; p = 0.01), and moderate-to-severe aortic regurgitation in BAV-AP (32.3% vs. 6.8% in BAV-RL; p < 0.0001). A normal aorta was the most common phenotype in BAV-AP patients (33.3% vs. 18.9% in BAV-RL; p = 0.037), and type 3 aortopathy was the most common phenotype in BAV-RL patients (40.5% vs. 9.7% in BAV-AP; p < 0.0001)., Conclusions: The patterns of valvular dysfunction and bicuspid aortopathy differed significantly between the 2 BAV phenotypes, suggesting the possibility of etiologically different entities., (Copyright © 2013 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Prevalence and antimicrobial resistance profiles of Salmonella serotypes isolated from 7 chicken meat brands produced by different integrated broiler operations in Korea were determined. In total, 210 samples were collected from retail supermarkets in Seoul, South Korea, and analyzed for the presence of Salmonella. Of 210 chicken meat samples, overall Salmonella prevalence was 22.4%. Salmonella Enteritidis was the dominant serovar, with an isolation rate of 57.4% from the Salmonella-positive chickens, followed by Salmonella Montevideo. Salmonella isolates frequently were resistant to various antibiotics, including 100% to erythromycin, 87% to cephalothin, 85% to nalidixic acid, and 70% to streptomycin. Of the 47 isolates, 41 (87.2%) isolates were resistant to 3 or more antibiotics. Moreover, the Salmonella profiles of each chicken meat brand were different by broiler operation. Brand A showed the highest prevalence of Salmonella (18 isolates, 60%), whereas brand G showed the lowest prevalence (one isolate, 3.3%). Eight among the 18 isolates of brand A were resistant to 11 antibiotics, whereas 5 of the 6 brand C isolates were resistant to only 2 antibiotics. This study demonstrates that a high proportion of chicken meat in Korea is contaminated with Salmonella and the prevalence and antimicrobial resistance patterns of Salmonella of chicken meat differ significantly according to the integrated broiler operation.

The pathogenicity of a fowl adenovirus serotype-1 (FAdV-1, K181 strain) isolated from a case of gizzard erosion in layer chickens was investigated in specific-pathogen-free (SPF) chicks. One-week-old SPF chicks were inoculated orally or intramuscularly with the isolate of FAdV-1 and euthanized for necropsy at 7, 14, and 21 d postinoculation. Although there were no clinical signs after inoculation, gizzard erosions were observed grossly and the virus was recovered from the gizzards in the inoculated chickens. Histologically, in the chickens that were infected orally, the lesions found in the gizzard consisted of severe degeneration and necrosis of glandular epitheliums and eosinophilic inclusion bodies. These results indicate that the Korean FAdV-1 isolate could induce gizzard lesions in chickens. Moreover, the present investigation reproduced an outbreak of gizzard erosion caused by FAdV-1 infection and, for the first time, described the isolation of FAdV-1 from chickens in Korea. These findings provide important information on the epidemiology and pathogenesis of FAdV-1 infection in chickens.

Background: Gefitinib was demonstrated to be synergistic with cisplatin and radiotherapy (RT) in in vitro studies. Biomarkers predictive of response to gefitinib in squamous cell head and neck cancer is still lacking., Methods: Thirty-one patients with locally advanced and easily accessible primary tumor sites for biopsies were recruited. Gefitinib was started 3 weeks before the start of cisplatin/concurrent radiotherapy (CTRT) and continued during the CTRT phase and thereafter for 4 months as consolidation phase. Two baselines and a repeat tumor sample were taken after 2 weeks of gefitinib alone to study its impact on tumor gene expression. Epidermal growth factor receptor (EGFR) protein expression, FISH and mutational status, and matrix metallopeptidase 11 (MMP11) protein expression were correlated with response and survival outcome., Results: The overall response rate to gefitinib alone was 9.7%. The survival outcome is as follows: median disease free 1.3 years, median survival time 2.4 years, 3-year disease free 42.9%, and 3-year overall survival 48.4%. EGFR FISH, protein expression, and mutational status did not predict for response nor survival outcome of patients. Although MMP11 overexpression did not predict for response, it predicted significantly for a poorer survival outcome., Conclusions: Gefitinib can be combined safely with cisplatin/RT. More studies are needed to uncover predictive biomarkers of benefit to gefitinib.

Objective: To report the clinical outcomes of highly active antiretroviral therapy (HAART)-naïve, human immunodeficiency virus (HIV)-positive patients with newly diagnosed cytomegalovirus (CMV) retinitis receiving intravitreal injections of a low-volume intermediate maintenance dose (1.0 mg/0.02 ml) of ganciclovir., Design: Nonrandomized, retrospective, interventional series., Participants: A consecutive cohort of 34 eyes from 24 HAART-naïve patients with AIDS and diagnosed with CMV retinitis by retinal specialists at the Singapore Communicable Disease Centre., Intervention: Patients received a maintenance dose of 1.0 mg/0.02 ml of intravitreal ganciclovir once weekly after standard induction therapy with 2.0 mg/0.04 ml of twice weekly intravitreal ganciclovir., Main Outcome Measures: Time to progression, visual acuity, and complications. Progression was observed using photographic documentation., Results: The median time to progression was 152 days (mean, 380.1 days, 95% confidence interval, 240.8-519.4). The median follow-up was 95 days (mean, 207.9 days). Three eyes developed rhegmatogenous detachments, but there was no endophthalmitis after 1858 injections. Contralateral involvement of CMV retinitis occurred in 17.6% of the patients. The cost estimate for intravitreal injections over a 6-month period was 11.7% that of sustained-release implants for unilateral treatment and 11.1% that of daily continuous intravenous infusions and oral valganciclovir compared with bilateral treatments., Conclusions: Weekly low-volume, intermediate-dose (1.0 mg/0.02 ml) ganciclovir is an efficacious option in developing countries where newer options of sustained-release implants and oral valganciclovir are unavailable or prohibitively expensive. The regimen maintains a long time to progression, preserving vision while minimizing retinal toxicity complications., (Copyright © 2012 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.)

O₆-methylguanine produced in DNA by the action of simple alkylating agents, such as N-methyl-N-nitrosourea (MNU), causes base-mispairing during DNA replication, thus leading to mutations and cancer. To prevent such outcomes, the cells carrying O⁶-methylguanine undergo apoptosis in a mismatch repair protein-dependent manner. We previously identified MAPO1 as one of the components required for the induction of apoptosis triggered by O⁶-methylguanine. MAPO1, also known as FNIP2 and FNIPL, forms a complex with AMP-activated protein kinase (AMPK) and folliculin (FLCN), which is encoded by the BHD tumor suppressor gene. We describe here the involvement of the AMPK-MAPO1-FLCN complex in the signaling pathway of apoptosis induced by O⁶-methylguanine. By the introduction of siRNAs specific for these genes, the transition of cells to a population with sub-G₁ DNA content following MNU treatment was significantly suppressed. After MNU exposure, phosphorylation of AMPKα occurred in an MLH1-dependent manner, and this activation of AMPK was not observed in cells in which the expression of either the Mapo1 or the Flcn gene was downregulated. When cells were treated with AICA-ribose (AICAR), a specific activator of AMPK, activation of AMPK was also observed in a MAPO1- and FLCN-dependent manner, thus leading to cell death which was accompanied by the depolarization of the mitochondrial membrane, a hallmark of the apoptosis induction. It is therefore likely that MAPO1, in its association with FLCN, may regulate the activation of AMPK to control the induction of apoptosis triggered by O⁶-methylguanine., (Copyright © 2011 Elsevier B.V. All rights reserved.)

Infectious bronchitis virus (IBV) infections cause great economic losses to the poultry industry worldwide, and the emergence of new variant strains complicates disease control. The present study investigated the genetic and protectotypic features of newly emerged Korean IBV strains. A phylogenetic analysis showed that several recent isolates formed 2 different clusters (new cluster 1 and 2), which were distinct from other preexisting clusters. New cluster 1 IBV strains represented recombinants between Korean nephropathogenic strain KM91 and the QXIBV strain. New cluster 2 IBV strains showed low amino acid homology (<58.7%) compared with previous isolates. We evaluated the protective efficacy of commercial IBV vaccines (H120 and K2 strain) against these new isolates. In cross-protection studies, the H120 strain did not provide sufficient protection against these variants. However, highly attenuated nephropathogenic IBV vaccine, K2 strain, provided significantly higher levels of protection against variants compared with chickens vaccinated with H120 (P < 0.05 or better). These results indicate that the K2 vaccine could be helpful for the reduction of economic losses caused by newly evolving IBV recombinants (new cluster 1) and variants (new cluster 2).

Background: Markers derived from dextrose (d-glucose) are observed in the MS/MS-based acylcarnitine profiles from dried-blood spots of some premature infants receiving intravenous nutrition. The presence of these markers at m/z 325, 399 and 473 are thought to arise from contamination of blood by total parenteral nutrition (TPN) solutions during specimen collection from premature infants. These solutions contain high concentrations of amino acids and as a result, false-positive screening results for amino acid disorders may occur. This study investigates quantitative parameters of dextrose and amino acids in blood samples enriched with different TPN solutions., Methods: Whole blood collected in heparin was enriched with three different TPN solutions containing 5, 10 or 12.5% dextrose and amino acids that were originally prepared for delivery of 2.5, 3 or 4 g/kg/day of Premasol® then spotted onto filter paper cards. Acylcarnitine and amino acid profiles using MS/MS were obtained. Ion ratios of dextrose relative to specific acylcarnitine stable isotope internal standards and amino acid concentrations were obtained., Results: The ion ratios for each of the dextrose markers at m/z 325, 399 and 473 exhibit linearity with the concentration of the dextrose component of TPN added to blood. The lowest detectable dextrose concentration added to blood was 7.6 mmol/l at 1:80 v/v TPN in blood. Furthermore, the concentrations of amino acids were linear with the concentration of the amino acid component of TPN added to blood. At the lowest detectable concentrations of dextrose marker, the amino acid concentrations were at or above the values considered abnormal in newborn screening laboratories. The molar ratios of amino acids approached the relative quantity of amino acid in the TPN solution with increasing enrichments in blood., Conclusions: Detection of the combinations of dextrose markers, very high elevations of amino acids and unusual molar ratios can be used to reject a specimen as improperly collected rather than declaring it a false positive and hence reduce false positive rates. This process enhances efficiency, reduces parental anxiety, and improves positive predictive values., (Copyright © 2011 Elsevier B.V. All rights reserved.)

Background: The use of tandem mass spectrometry (MS/MS) for the analysis of amino acids and acylcarnitines from dried-blood spots (DBS) has become routine practice in newborn screening laboratories. The Newborn Screening Quality Assurance Program (NSQAP) added 3-hydroxyisovalerylcarnitine (C5OH) into its routine quality control and proficiency testing (PT) DBS materials for MS/MS to assure the quality of C5OH screening. We report the results from NSQAP evaluations for C5OH-enriched DBS, and summarize participant screening practices based on their analytical methods., Methods: NSQAP prepared C5OH-enriched DBS materials for its participants. Laboratories reported quantitative and qualitative results. Bias plots of quantitative results were constructed using reported data and the results were sorted by an analytical method., Results: NSQAP participants reported PT specimen 3964 as outside of normal limits for C5OH. The mean C5OH value for derivatized and non-derivatized methods was 2.80 and 2.67 μmol/l, respectively. Reported data from other specimens showed a similar trend in derivatized vs. non-derivatized assay results. Differences in C5OH quantitative values were observed among laboratories using different internal standards., Conclusions: C5OH MS/MS measurements in DBS assays varied by method and the choice of internal standards. The use of NSQAP's DBS materials allows harmonization of C5OH measurements by newborn screening laboratories worldwide., (Published by Elsevier B.V.)

Background: The false positive rate for the newborn screening of disorders of amino acid metabolism for premature infants is higher than full term infants. This may be due to very low birth weight infants receiving high concentrations of amino acids from total parenteral nutrition (TPN) administration and/or immature metabolism. An investigation of the possible influence of TPN on screening of premature infants resulted in the detection of three unusual peaks in the tandem mass spectrometry (MS/MS) acylcarnitine profile. These markers were closely correlated with the detection of very high multiple amino acid increases in the profiles of newborns administered with TPN and who were ultimately found to be normal and free of inherited metabolic disorders., Methods: TPN solutions contain a concentrated mixture of amino acids and dextrose and other nutrients in saline. Due to its high concentration and suggestion of a carbohydrate, it was hypothesized that dextrose (D-glucose) was the contaminant and source of the markers detected. Dextrose, stable isotope-labeled 13C6-dextrose and various TPN solutions were analyzed directly or after enrichment in whole blood by multiple MS/MS acquisition modes including MS-only, product and precursor ion and neutral loss scans., Results: Analysis of dried-blood spots (DBS) prepared from whole blood spiked with TPN solutions containing 12.5% dextrose and amino acid formulations designed to deliver 2.5 gm/kg/day of an amino acid mixture had moderate increases of all 3 dextrose markers detected at m/z 325, 399 and 473 as compared to controls. MS-only scans, product and precursor ion scans of dextrose and 13C6-dextrose in positive ion mode confirmed that these 3 peaks are derived from dextrose. Mass spectral analysis of labeled and unlabeled dextrose suggested that these peaks were dimers derived from dextrose., Conclusion: The identification of dextrose markers in DBS indicates that high concentrations of dextrose were present in blood and the likely source was contamination by TPN solutions most likely occurring during a sample collection process., (2010 Elsevier B.V. All rights reserved.)

Background: The analysis of amino acids (AA) and acylcarnitines (AC) by tandem mass spectrometry (MS/MS) is performed in newborn screening laboratories worldwide. While butyl esterification assays are routine, it is possible to detect AAs and ACs as their native free acids (underivatized). The Centers for Disease Control and Prevention's Newborn Screening Quality Assurance Program provides dried blood spot (DBS) quality control (QC) and proficiency testing (PT) programs for numerous MS/MS analytes. We describe empirical differences between derivatization and non-derivatization techniques for selected AAs and ACs., Methods: DBS materials were prepared at levels near, above and below mean domestic laboratory cut-offs, and distributed to program participants for MS/MS analysis. Laboratories reported quantitative and qualitative results. QC DBS materials were assayed in-house following established protocols., Result: Minor differences (<15%) between quantitative values resulting from butyl esters and free acid techniques were observed for the majority of the analytes. Mass spectrometric response from underivatized dicarboxylic acid acylcarnitines was less intense than their butyl esters., Conclusions: The use of underivatized techniques may also result in the inability to differentiate isobaric acylcarnitines. Laboratories should establish their own protocols by focusing on the decisions that identify test results requiring additional follow-up testing versus those that do not., (Published by Elsevier B.V.)

Atherosclerosis is a chronic inflammatory disease that involves the recruitment of leukocytes to the arterial wall. Leukotactin-1 (Lkn-1), a new member of the CC chemokine family, is a potent chemoattractant for leukocytes and thus is implicated in inflammatory diseases. In this study, we investigated the possible association of Lkn-1 with human atherosclerosis. Atherosclerotic lesion and plasma samples were obtained from atherosclerotic patients. Human THP-1 monocyte-derived foam cells were prepared by treatment with an oxidized low-density lipoprotein. The expression level of Lkn-1 or its receptors mRNA was measured by RT-PCR analysis. Levels of plasma Lkn-1, MCP-1, ICAM-1 and total cholesterol were measured by ELISA or enzymatic assay. Lkn-1 expression was markedly enhanced not only at the mRNA level in human atherosclerotic lesions, but also at the circulating level in atherosclerosis patients compared with normal subjects. An in vitro study revealed that the level of Lkn-1 release was significantly enhanced by oxidative stress or proatherogenic mediators in macrophages and macrophage-derived foam cells. Lkn-1 stimulated endothelial cells to release ICAM-1, which is implicated in atherogenesis. Taken together, our data suggest that Lkn-1 plays an important role in the development of atherosclerosis.

Purpose: Partial excision with triceps reattachment is an accepted method for treating comminuted fractures of the olecranon. The currently recommended site for reattachment is along the articular margin of the remaining olecranon process. With computer models suggesting that this may lead to weakness of elbow extension, this study was performed to evaluate different sites for triceps reattachment with respect to extension strength of the elbow., Method: Ten fresh frozen human cadavers were potted and the elbow placed in varying degrees of flexion (45 degrees, 90 degrees, and 135 degrees ). Incremental loads were applied to the triceps mechanism and the force generated was recorded using an Instron materials testing machine (Instron Corp., Canton, MA). A 50% olecranon excision was then performed, simulating a comminuted olecranon fracture. The triceps tendon was attached either anteriorly along the articular margin or posteriorly along the cortical margin. All specimens were tested at both insertion sites in random order., Results: A significant decrease in extension strength was observed between intact specimens and anterior attachment of the triceps tendon at all angles of elbow flexion. A decrease was only observed with posterior reattachment at 90 degrees. Posterior reattachment provided greater extensor strength than anterior attachment, with greatest differences seen at increasing positions of elbow extension., Conclusions: Although anterior reattachment of the triceps tendon after partial excision of the olecranon is currently recommended by some, this results in diminished strength of the triceps mechanism. A greater mechanical advantage with increased strength is provided by a more posterior reattachment using the technique described. These differences are greatest at increasing positions of elbow extension where triceps strength is more functionally important.

Study Objectives: To investigate changes in the cerebral metabolism of patients with COPD, using localized in vivo proton magnetic resonance spectroscopy ((1)H MRS), and to evaluate the clinical significance of cerebral metabolic abnormalities in COPD patients., Patients and Methods: Seventeen symptomatic COPD patients and 21 age-matched healthy volunteers participated in this study. All subjects underwent (1)H MRS, and neuropsychological tests (Wechsler memory scale-revised [WMS-R], color trail test, and grooved pegboard test) were performed by COPD patients. Magnetic resonance spectra were obtained from localized regions of parietal white matter (PWM) and occipital gray matter (OGM). Absolute levels of N-acetyl aspartate (NAA), creatine (Cr), choline (Cho), and myo-inositol (mI) were calculated., Results: In COPD patients, the mean (+/- SD) FEV(1) was 38 +/- 10% predicted, the PaCO(2) was 39 +/- 7 mm Hg, and the PaO(2) was 89 +/- 18 mm Hg, and these values did not exhibit statistical correlation with the levels of cerebral metabolites. NAA, Cr, and Cho levels in PWM were all significantly lower in COPD patients than in control subjects (p < 0.0125 [Bonferroni adjusted]). Neuropsychological parameters were lower in COPD patients compared with standardized values. However, they were not correlated with the levels of cerebral metabolites except for a positive correlation between the Cho level in PWM and the general memory quotient of WMS-R (r = 0.52; p < 0.05)., Conclusions: Our results demonstrate that the cerebral metabolism is significantly altered in symptomatic COPD patients. The relationship between decreased Cho levels and memory dysfunction, and the clinical significance of other cerebral metabolic changes in COPD patients need to be further investigated.

Objective: The aim of this study was to investigate the subjective visual experience of patients during phacoemulsification and intraocular lens (IOL) implantation under topical anesthesia., Design: Postoperative questionnaire survey., Participants: The study cohort consisted of 52 patients with cataracts. There were 18 male (34.6%) and 34 female (65.4%) patients. Their mean (+/- SD) age was 67.5 (+/-10.8) years., Intervention: The patients underwent routine phacoemulsification and IOL implantation under topical anesthesia., Main Outcome Measures: The patients were interviewed on the same day after their operation regarding their visual experience in the operated eye during surgery., Results: All patients (100%) reported that they could see at least some light during the surgery. Some patients reported they could also see one or more colors (50 patients, 96.2%), movements (32 patients, 61.5%), flashes (24 patients, 46.2%), the surgeon's fingers/hands (13 patients, 25%), instruments (12 patients, 23.1%), and/or the surgeon (4 patients, 7.7%). The colors seen included red (24 patients, 46.2%), yellow (23 patients, 44.2%), blue (12 patients, 23.1%), green (7 patients, 13.5%), and orange (6 patients, 11.5%). Eight patients (15.4%) saw the spectrum of colors similar to that of the rainbow. Twenty-four patients (46.2%) reported that the brightness of light changed during the course of the operation. Eight patients (15.4%) found their visual experience frightening. There was no statistically significant association between those who found the visual experience frightening and the sex or age of the patient, a history of cataract operation in the fellow eye, the type of visual sensation experienced, or the presence of coexisting ocular pathology., Conclusion: All patients undergoing phacoemulsification under topical anesthesia experience a variety of visual sensations that may be frightening in a small proportion of patients.

A wide variety of MRI techniques is available for vascular imaging, each exploiting a different property of flowing blood to achieve contrast. These include spin-echo, which has been used for the diagnosis of aortic dissection and of great vessel anomalies, as well as for the evaluation of pulmonary flow in patients with pulmonary hypertension and pulmonary embolism. Spin echo excels in detecting infection and hematoma in the tissues around grafts and vessels. Phase display imaging has proven useful in differentiating signal of slow flow from that of intravascular thrombus. Imaging of peripheral vessels can be achieved with gradient refocused sequences, which provide bright intravascular signal over a wide range of flow velocities. These sequences may be combined with subtraction strategies to eliminate the signal from stationary tissues in order to generate an angiographic image. The advent of three-dimensional MR angiographic imaging techniques provides an effective way to display peripheral vessels. Early experience implies that MR angiography will play an important role in vascular imaging in the future, provided that the signal loss from turbulent flow can be minimized.