Percutaneous Mitral Valve Repair in Mitral Regurgitation Reduces Cell-Free Hemoglobin and Improves Endothelial Function

Background and Objective

Endothelial dysfunction is predictive for cardiovascular events and may be caused by decreased bioavailability of nitric oxide (NO). NO is scavenged by cell-free hemoglobin with reduction of bioavailable NO up to 70% subsequently deteriorating vascular function. While patients with mitral regurgitation (MR) suffer from an impaired prognosis, mechanisms relating to coexistent vascular dysfunctions have not been described yet. Therapy of MR using a percutaneous mitral valve repair (PMVR) approach has been shown to lead to significant clinical benefits. We here sought to investigate the role of endothelial function in MR and the potential impact of PMVR.

Methods and Results

Twenty-seven patients with moderate-to-severe MR treated with the MitraClip® device were enrolled in an open-label single-center observational study. Patients underwent clinical assessment, conventional echocardiography, and determination of endothelial function by measuring flow-mediated dilation (FMD) of the brachial artery using high-resolution ultrasound at baseline and at 3-month follow-up. Patients with MR demonstrated decompartmentalized hemoglobin and reduced endothelial function (cell-free plasma hemoglobin in heme 28.9±3.8 μM, FMD 3.9±0.9%). Three months post-procedure, PMVR improved ejection fraction (from 41±3% to 46±3%, p = 0.03) and NYHA functional class (from 3.0±0.1 to 1.9±1.7, p<0.001). PMVR was associated with a decrease in cell free plasma hemoglobin (22.3±2.4 μM, p = 0.02) and improved endothelial functions (FMD 4.8±1.0%, p<0.0001).

Conclusion

We demonstrate here that plasma from patients with MR contains significant amounts of cell-free hemoglobin, which is accompanied by endothelial dysfunction. PMVR therapy is associated with an improved hemoglobin decompartmentalization and vascular function.     

Ingestion of a Cold Temperature/Menthol Beverage Increases Outdoor Exercise Performance in a Hot,Humid Environment

Purpose

A recent laboratory study demonstrated that the ingestion of a cold/menthol beverage improved exercise performance in a hot and humid environment during 20 km of all-out cycling. Therefore, the aim of this study was to determine whether the ingestion of cold water/ice-slurry with menthol would improve performance in hot and humid outdoor conditions.

Methods

Ten trained males completed three trials of five blocks consisting of 4-km cycling and 1.5-km running. During warm-up, every block and recovery, the athletes drank 190 ml of aromatized (i.e., with 0.05 mL of menthol) beverage at three temperatures: Neutral (ambient temperature) (28.7°C±0. 5°C), Cold (3.1°C±0.6°C) or Ice-slurry (0.17°C±0.07°C). Trial time, core temperature (T_co), heart rate (HR), rate of perceived exertion (RPE), thermal sensation (TS) and thermal comfort (TC) were assessed.

Results

Ice-slurry/menthol increased performance by 6.2% and 3.3% compared with neutral water/menthol and cold water/menthol, respectively. No between-trial differences were noted for T_co, HR, RPE, TC and TS was lower with ice-slurry/menthol and cold water/menthol compared with neutral water/menthol.

Conclusion

A low drink temperature combined with menthol lessens the performance decline in hot/humid outdoor conditions (i.e., compared with cold water alone). Performances were better with no difference in psycho-physiological stress (T_co, HR and RPE) between trials. The changes in perceptual parameters caused by absorbing a cold/menthol beverage reflect the psychological impact. The mechanism leading to these results seems to involve brain integration of signals from physiological and psychological sources.     

Nutrition Concerns of Insufficient and Excessive Intake of Dietary Minerals in Lactating Women: A Cross-Sectional Survey in Three Cities of China

Objective

Objectives of this study were 1) to investigate the mineral intake by Chinese lactating women, 2) to explore the dietary source of minerals, and 3) the ratios between different dietary minerals.

Methods

A total of 468 lactating women in 5–240 days post-partum participated in this study. Food intakes by participants were measured using one time of 24-hour dietary recall, and minerals from food were calculated based on the Chinese Food Composition Table, second edition.

Results

In post-partum, women had inadequate food intake. 81.0% of women’s daily intake of dairy products was lower than 300g, and 97.1% of women’s daily intake of salt over 6g. For mineral intake, there were 81.8%, 59.0%, 47.6%, 45.7% and 66.8% of women’s calcium, magnesium, iron, zinc and selenium intake lower than the estimated average requirement, respectively, and 91.7% of women’s excessive intake of sodium. The calcium/phosphorus and sodium/potassium ratios were 0.41±0.26/1 and 3.13±2.89/1, respectively. Considering the dietary sources of minerals, 27.3%, 25.3% and 30.1% of iron, zinc and calcium were from animal-based food, respectively, and 60.3%, 66.1% and 58.0% of iron, zinc and calcium were from plant-based food, respectively. The phosphorus-protein ratio was 0.014±0.003/1. Lactation stage was associated with nutrient intake. Women within 30 days post-partum and the ones who live in Guangzhou had a significantly lower intake of certain minerals, while women with a high education experience had a high intake of calcium, potassium, iron and zinc. Productive age, whether obese or not, and delivery ways were not associated with mineral intakes (P all >0.05).

Conclusion

Chinese women in three studied cities had an inappropriate food intake and resulted in both insufficient and excessive intakes of certain minerals.     

HbA1c Levels Are Associated with Chronic Kidney Disease in a Non-Diabetic Adult Population: A Nationwide Survey (KNHANES 2011–2013)

Background

Many studies have reported an association between glycated hemoglobin A1c (HbA1c) and metabolic syndrome (MetS) in non-diabetes patients. Each component of MetS is in fact related to chronic kidney disease (CKD) incidence and progression. Therefore, HbA1c in non-diabetic mellitus (DM) may be intrinsically associated with the prevalence of CKD. The hypothesis of the present study was that high HbA1c in non-DM patients is associated with CKD.

Patients and Methods

The total number of participants in this study was 24,594. The participants were divided into three groups according to their HbA1c levels: a Low group (<5.7% or <39 mmol/mol), a Middle group (5.7–6.0% or 39–42 mmol/mol), and a High group (>6.0% or >42 mmol/mol). The estimated glomerular filtration rate (eGFR) was calculated using the Chronic Kidney Disease Epidemiology Collaboration equation.

Results

The number of participants allocated to the Low, Middle, and High groups was 8,651, 4,634, and 1,387, respectively. Linear regression analyses were performed to evaluate the association between variables. Standardized β ± standard error was 0.25 ± 0.22 for waist circumference, 0.44 ± 0.20 for fasting glucose, –0.14 ± 0.30 for high-density lipoprotein cholesterol levels, 0.15 ± 2.31 for triglyceride levels, 0.21 ± 0.00 for systolic blood pressure, 0.10 ± 0.00 for diastolic blood pressure, and –0.22 ± 0.42 for eGFR (P < 0.001 for all variables). eGFR in non-diabetes participants was inversely associated with the HbA1c level, where eGFR decreased as HbA1c levels increased. Standardized βs were –0.04 ± 0.42 in multivariable analysis (P < 0.001). The proportion of participants with only MetS, only CKD, or both MetS and CKD was higher in the High group than in the Low and Middle groups.

Conclusion

High HbA1c in non-DM patients may be associated with CKD. Renal function in patients with high HbA1c levels may need to be monitored.     

Elevated Steady State WBC and Platelet Counts Are Associated with Frequent Emergency Room Use in Adults with Sickle Cell Anemia

Introduction

Sickle cell anemia has many sequelae that result in emergency department (ED) use, but a minority of patients with sickle cell disease are frequent utilizers and make up the majority of ED visits. If patients who are likely to be frequent ED can be identified in steady state, they can be treated with disease modifying agents in an attempt to reduce ED use frequency. We sought to identify steady state markers for frequent ED use.

Methods

We identified all patients with SS/Sβ0 seen at our facilities in 2012. Health care utilization over the entire year was calculated and ED visit numbers categorized as either 0–1, 2–5, or 6 or more visits a year. Steady state and acutely active laboratory parameters were collected and analyzed using analysis of variance models and odds ratios.

Results

432 adult sickle cell patients were identified, ages 18–87, 54% female, and 38% had been prescribed hydroxyurea. Of the 432 patients,192 had 0–1 visits in the year, 144 had 2–5 visits in the year, and 96 had >6 visits for a total of 2259 visits. Those who had >6 visits accounted for 1750 (77%) of the total visits for the year. When steady state laboratory markers were examined, each additional 50x109/L platelets was associated with 22% greater risk (p < .001); each 1x109/L of WBC was associated with 11% greater risk (p = .003), and each 1g/dL Hb was associated with 23% lower risk (p = .007) of >6 ED visits/year. We did not observe a relationship between baseline HbF, LDH or reticulocyte count with >6 ED visits.

Conclusion

Patients with elevated white blood cell counts, elevated platelet counts, and low hemoglobin levels exhibited higher risk for frequent ED utilization and could be candidates for early and aggressive therapy with disease modifying agents.     

Association between Low-Grade Albuminuria and Cardiovascular Risk in Korean Adults: The 2011–2012 Korea National Health and Nutrition Examination Survey

Background

Recent studies have indicated that low UACR levels (<30 μg/mg) previously considered to be in the normal range (‘low-grade albuminuria’) are associated with cardiovascular morbidity and mortality in the general population.

Methods

We studied 9,736 participants with albuminuria in the normal range from the 2011–2012 Korea National Health and Nutrition Examination Survey (KNHANES).

Results

The weighted prevalences of metabolic syndrome (MS) and the 10-year risk for coronary heart disease measured using the Framingham risk score (FRS) ≥ 20% (high risk) were 22.5 ± 0.7% and 14.5 ± 0.7%, respectively, in males and 23.3 ± 0.8% and 8.5 ± 0.4%, respectively in females. Weighted comparisons among the tertiles of UACR revealed that the prevalences of MS and high-risk FRS increased with increasing UACR (MS: males, 15.9 ± 1.1, 20.2 ± 1.2, 32.4 ± 1.5%, respectively; P < 0.001; and females, 17.6 ± 1.0, 22.7 ± 1.0, 30.2 ± 1.4%, respectively; P < 0.001. High-risk FRS: males, 9.5 ± 0.7, 12.3 ± 0.9, 22.5 ± 1.2, respectively; P < 0.001; and females, 5.8 ± 0.6, 7.9 ± 0.7, 12.0 ± 0.9%, respectively; P < 0.001). The positive association persisted after adjusting for hypertension and diabetes. The weighted comparisons among the deciles of UACR revealed that the prevalences of MS and high-risk FRS began to increase at the ranges of 3.89–5.15 and 5.16–7.36 mg/g Cr, respectively.

Conclusion

Low-grade albuminuria was significantly associated with estimated cardiovascular risk and MS in a nationally representative sample of Koreans.     

Ocular Dominance Is Associated with the Ganglion Cell-Inner Plexiform Layer Thickness Profile in the Macula

Purpose

To investigate the characteristics of macular ganglion cell-inner plexiform layer (GCIPL) thickness profiles associated with ocular dominance.

Setting

Private practice, Seoul, Republic of Korea.

Design

Comparative case-control study.

Methods

Both eyes of 199 participants with no ophthalmic abnormalities were included. Participants were imaged by spectral-domain optical coherence tomography, and underwent dominant eye testing using a hole-in-a-card test (sighting dominance) at the same visit. Macular GCIPL, as well as circumpapillary retinal nerve fiber layer (RNFL) thickness were compared for individual patients, according to ocular dominance.

Results

Ocular dominance occurred predominantly in the right eye (right vs. left: 72.36 vs. 27.60%; P < 0.001). In the comparison of macular GCIPL thickness, the average (81.27±5.01 μm vs. 80.66±6.31 μm in dominant vs. non-dominant eyes), inferonasal (81.39±5.47μm vs. 80.33±6.82μm, and inferior sectors (77.95±6.05μm vs. 76.97±8.15μm) were significantly different between dominant and non-dominant eyes (P = 0.040, 0.005, and 0.032, respectively). Significant predictors of average GCIPL thickness were spherical equivalent (β = 1.37, P<0.001), astigmatic power (β = 1.44, P = 0.009), disc area (β = 3.90, P < 0.001), average RNFL thickness (β = 0.22, P<0.001), average cup-to-disc ratio (β = 5.74, P = 0.002), difference between the inferior and superior quadrant RNFL thicknesses (β = 0.08, P = 0.024), and ocular dominance (β = 2.10, P = 0.020). On multivariate regression analysis, ocular dominance was correlated with average GCIPL thickness after adjusting for potential confounders (β = 1.63, P = 0.048).

Conclusions

Dominant eyes accompanied significantly thicker average macular GCIPL. This information suggests that macular GCIPL thickness may provide an indicator of the relative dominance of an eye.     

Pharmacological Modulation of Hemodynamics in Adult Zebrafish In Vivo

Introduction

Hemodynamic parameters in zebrafish receive increasing attention because of their important role in cardiovascular processes such as atherosclerosis, hematopoiesis, sprouting and intussusceptive angiogenesis. To study underlying mechanisms, the precise modulation of parameters like blood flow velocity or shear stress is centrally important. Questions related to blood flow have been addressed in the past in either embryonic or ex vivo-zebrafish models but little information is available for adult animals. Here we describe a pharmacological approach to modulate cardiac and hemodynamic parameters in adult zebrafish in vivo.

Materials and Methods

Adult zebrafish were paralyzed and orally perfused with salt water. The drugs isoprenaline and sodium nitroprusside were directly applied with the perfusate, thus closely resembling the preferred method for drug delivery in zebrafish, namely within the water. Drug effects on the heart and on blood flow in the submental vein were studied using electrocardiograms, in vivo-microscopy and mathematical flow simulations.

Results

Under control conditions, heart rate, blood flow velocity and shear stress varied less than ± 5%. Maximal chronotropic effects of isoprenaline were achieved at a concentration of 50 μmol/L, where it increased the heart rate by 22.6 ± 1.3% (n = 4; p < 0.0001). Blood flow velocity and shear stress in the submental vein were not significantly increased. Sodium nitroprusside at 1 mmol/L did not alter the heart rate but increased blood flow velocity by 110.46 ± 19.64% (p = 0.01) and shear stress by 117.96 ± 23.65% (n = 9; p = 0.03).

Discussion

In this study, we demonstrate that cardiac and hemodynamic parameters in adult zebrafish can be efficiently modulated by isoprenaline and sodium nitroprusside. Together with the suitability of the zebrafish for in vivo-microscopy and genetic modifications, the methodology described permits studying biological processes that are dependent on hemodynamic alterations.     

Storage Temperature Alters the Expression of Differentiation-Related Genes in Cultured Oral Keratinocytes

Purpose

Storage of cultured human oral keratinocytes (HOK) allows for transportation of cultured transplants to eye clinics worldwide. In a previous study, one-week storage of cultured HOK was found to be superior with regard to viability and morphology at 12°C compared to 4°C and 37°C. To understand more of how storage temperature affects cell phenotype, gene expression of HOK before and after storage at 4°C, 12°C, and 37°C was assessed.

Materials and Methods

Cultured HOK were stored in HEPES- and sodium bicarbonate-buffered Minimum Essential Medium at 4°C, 12°C, and 37°C for one week. Total RNA was isolated and the gene expression profile was determined using DNA microarrays and analyzed with Partek Genomics Suite software and Ingenuity Pathway Analysis. Differentially expressed genes (fold change > 1.5 and P < 0.05) were identified by one-way ANOVA. Key genes were validated using qPCR.

Results

Gene expression of cultures stored at 4°C and 12°C clustered close to the unstored control cultures. Cultures stored at 37°C displayed substantial change in gene expression compared to the other groups. In comparison with 12°C, 2,981 genes were differentially expressed at 37°C. In contrast, only 67 genes were differentially expressed between the unstored control and the cells stored at 12°C. The 12°C and 37°C culture groups differed most significantly with regard to the expression of differentiation markers. The Hedgehog signaling pathway was significantly downregulated at 37°C compared to 12°C.

Conclusion

HOK cultures stored at 37°C showed considerably larger changes in gene expression compared to unstored cells than cultured HOK stored at 4°C and 12°C. The changes observed at 37°C consisted of differentiation of the cells towards a squamous epithelium-specific phenotype. Storing cultured ocular surface transplants at 37°C is therefore not recommended. This is particularly interesting as 37°C is the standard incubation temperature used for cell culture.     

Interactive Video Game Cycling Leads to Higher Energy Expenditure and Is More Enjoyable than Conventional Exercise in Adults

Background

Despite the widely accepted health benefits of regular physical activity, only a small percentage of the population meets the current recommendations. The reasons include a wide use of technology and a lack of enjoyment while exercising. The purpose of this study was to compare the physiological, perceptual and enjoyment responses between a single bout of (I) conventional cycling and (II) interactive cycling video game at a matched workload.

Methods

A cross-sectional study in 34 healthy participants was performed. Initially, participants completed an incremental maximal cycling test to measure peak oxygen uptake and to determine ventilatory threshold. In random order, participants carried out a 30 min interactive cycling trial and a 30 min conventional cycling trial at 55% of peak power output. During the trials, oxygen uptake and energy expenditure were measured by open-circuit spirometry and heart rate was measured by radiotelemetry. RPE and enjoyment were measured every 10 minutes with Borg scale and a modified PACES scale.

Results

Interactive cycling resulted in a significantly greater %V̇O₂Reserve (68.2% ± 9.2% vs 64.7% ± 8.1%), rate of energy expenditure (505.8±75.2 vs 487.4±81.2 j·kg^-1·min^-1), and enjoyment (63.4% ± 17 vs 42% ± 13.6), P&lt;0.05. Participants were working at a higher intensity in relation to the individual’s ventilatory threshold during the interactive cycling video game trial (M = 11.86, SE = 3.08) than during the Conventional cycling trial (M = 7.55, SE = 3.16, t(33) = -2.69, P&lt;0.05, r = .42). No significant differences were found for heart rate reserve (72.5 ± 10.4 vs 71.4±10.1%) and RPE (13.1 ± 1.8 vs 13.2 ± 1.7).

Conclusion

Interactive cycling games can be a valid alternative to conventional exercise as they result in a higher exercise intensity than conventional cycling and a distraction from aversive cognitive and physiological states at and above the ventilatory threshold.     

Serum Levels of the Cancer-Testis Antigen POTEE and Its Clinical Significance in Non-Small-Cell Lung Cancer

Background

POTEE (POTE ankyrin domain family, member E) is a newly identified cancer-testis antigen that has been found to be expressed in a wide variety of human cancers including cancers of the colon, prostate, lung, breast, ovary, and pancreas.

Aim

To measure the serum levels of POTEE in patients with non-small-cell lung cancer (NSCLC) and to explore the clinical significance of POTEE in NSCLC.

Patients and Methods

104 NSCLC patients, 66 benign lung disease patients and 80 healthy volunteers were enrolled in this study from May 2013 to February 2014. Serum POTEE levels were measured using enzyme-linked immunosorbent assay (ELISA). Numerical variables were recorded as means ± standard deviation (SD) and analyzed by independent t tests. Categorical variables were calculated as rates and were analyzed using a χ² test or Fisher’s exact test. Survival curves were estimated and compared using the Kaplan-Meier method and log-rank tests.

Results

Serum POTEE levels were significantly higher in NSCLC patients than in benign lung disease patients and healthy controls (mean ± SD [pg/ml], 324.38± 13.84 vs. 156.93 ± 17.38 and 139.09 ± 15.80, P<0.001) and were significantly correlated with TNM stage. Survival analysis revealed that patients with low serum POTEE had longer progression-free survival (PFS) than those with high serum POTEE (P=0.021). Cox multivariate analysis indicated that POTEE was an independent prognostic factor of progression-free survival (P =0.009, hazard ratio, 2.440).

Conclusions

Serum POTEE level in NSCLC patients is associated with TNM stage and is a potential prognostic factor.     

Packed Red Blood Cells Are an Abundant and Proximate Potential Source of Nitric Oxide Synthase Inhibition

Objective

We determined, for packed red blood cells (PRBC) and fresh frozen plasma, the maximum content, and ability to release the endogenous nitric oxide synthase (NOS) inhibitors asymmetric dimethylarginine (ADMA) and monomethylarginine (LNMMA).

Background

ADMA and LNMMA are near equipotent NOS inhibitors forming blood’s total NOS inhibitory content. The balance between removal from, and addition to plasma determines their free concentrations. Removal from plasma is by well-characterized specific hydrolases while formation is restricted to posttranslational protein methylation. When released into plasma they can readily enter endothelial cells and inhibit NOS. Fresh rat and human whole blood contain substantial protein incorporated ADMA however; the maximum content of ADMA and LNMMA in PRBC and fresh frozen plasma has not been determined.

Methods

We measured total (free and protein incorporated) ADMA and LNMMA content in PRBCs and fresh frozen plasma, as well as their incubation induced release, using HPLC with fluorescence detection. We tested the hypothesis that PRBC and fresh frozen plasma contain substantial inhibitory methylarginines that can be released chemically by complete in vitro acid hydrolysis or physiologically at 37°C by enzymatic blood proteolysis.

Results

In vitro strong-acid-hydrolysis revealed a large PRBC reservoir of ADMA (54.5 ± 9.7 µM) and LNMMA (58.9 ± 28.9 μM) that persisted over 42-d at 6° or -80°C. In vitro 5h incubation at 37°C nearly doubled free ADMA and LNMMNA concentration from PRBCs while no change was detected in fresh frozen plasma.

Conclusion

The compelling physiological ramifications are that regardless of storage age, 1) PRBCs can rapidly release pathologically relevant quantities of ADMA and LNMMA when incubated and 2) PRBCs have a protein-incorporated inhibitory methylarginines reservoir 100 times that of normal free inhibitory methylarginines in blood and thus could represent a clinically relevant and proximate risk for iatrogenic NOS inhibition upon transfusion.     

Low-Volume High-Intensity Interval Training in a Gym Setting Improves Cardio-Metabolic and Psychological Health

Background

Within a controlled laboratory environment, high-intensity interval training (HIT) elicits similar cardiovascular and metabolic benefits as traditional moderate-intensity continuous training (MICT). It is currently unclear how HIT can be applied effectively in a real-world environment.

Purpose

To investigate the hypothesis that 10 weeks of HIT, performed in an instructor-led, group-based gym setting, elicits improvements in aerobic capacity (VO_2max), cardio-metabolic risk and psychological health which are comparable to MICT.

Methods

Ninety physically inactive volunteers (42±11 y, 27.7±4.8 kg.m^-2) were randomly assigned to HIT or MICT group exercise classes. HIT consisted of repeated sprints (15–60 seconds, >90% HR_max) interspersed with periods of recovery cycling (≤25 min.session^-1, 3 sessions.week^-1). MICT participants performed continuous cycling (~70% HR_max, 30–45 min.session^-1, 5 sessions.week^-1). VO_2max, markers of cardio-metabolic risk, and psychological health were assessed pre and post-intervention.

Results

Mean weekly training time was 55±10 (HIT) and 128±44 min (MICT) (p<0.05), with greater adherence to HIT (83±14% vs. 61±15% prescribed sessions attended, respectively; p<0.05). HIT improved VO_2max, insulin sensitivity, reduced abdominal fat mass, and induced favourable changes in blood lipids (p<0.05). HIT also induced beneficial effects on health perceptions, positive and negative affect, and subjective vitality (p<0.05). No difference between HIT and MICT was seen for any of these variables.

Conclusions

HIT performed in a real-world gym setting improves cardio-metabolic risk factors and psychological health in physically inactive adults. With a reduced time commitment and greater adherence than MICT, HIT offers a viable and effective exercise strategy to target the growing incidence of metabolic disease and psychological ill-being associated with physical inactivity.     

RGD-Targeted Ultrasound Contrast Agent for Longitudinal Assessment of Hep-2 Tumor Angiogenesis In Vivo

Objective

To prepare arginine-glycine-aspartate (RGD)-targeted ultrasound contrast microbubbles (MBs) and explore the feasibility of their use in assessing dynamic changes in αvβ3 integrin expression in a murine model of tumor angiogenesis.

Methods

RGD peptides were conjugated to the surfaces of microbubbles via biotin-avidin linkage. Microbubbles bearing RADfK peptides were prepared as controls. The RGD-MBs were characterized using an Accusizer 780 and optical microscopy. The binding specificity of the RGD-MBs for ανβ3-expressing endothelial cells (bEnd.3) was demonstrated in vitro by a competitive inhibition experiment. In an in vivo study, mice bearing tumors of three different stages were intravenously injected with RGD-MBs and subjected to targeted, contrast-enhanced, high-frequency ultrasound. Subsequently, tumors were harvested and sectioned for immunofluorescence analysis of ανβ3 expression.

Results

The mean size of the RGD-MBs was 2.36 ± 1.7 μm. The RGD-MBs showed significantly higher adhesion levels to bEnd.3 cells compared to control MBs (P < 0.01). There was rarely binding of RGD-MBs to αvβ3-negative MCF-7 cells. Adhesion of the RGD-MBs to the bEnd.3 cells was significantly inhibited following treatment with anti-alpha(v) antibodies. The quantitative acoustic video intensity for high-frequency, contrast-enhanced ultrasound imaging of subcutaneous human laryngeal carcinoma (Hep-2) tumor xenografts was significantly higher in small tumors (19.89 ± 2.49) than in medium tumors (11.25 ± 2.23) and large tumors (3.38 ± 0.67) (P < 0.01).

Conclusions

RGD-MBs enable noninvasive in vivo visualization of changes in tumor angiogenesis during tumor growth in subcutaneous cancer xenografts.     

Hypoglycemia and Medical Expenses in Patients with Type 2 Diabetes Mellitus: An Analysis Based on the Korea National Diabetes Program Cohort

Background and Aims

Hypoglycemia is one of the most important adverse events in individuals with type 2 diabetes mellitus (T2DM). However, hypoglycemia-related events are usually overlooked and have been documented less in clinical practice.

Materials and Methods

We evaluated the incidence, clinical characteristics, and medical expenses of hypoglycemia related events in T2DM patients based on the Korea National Diabetes Program (KNDP), which is the largest multi-center, prospective cohort in Korea (n = 4,350). For accurate outcomes, the KNDP data were merged with claims data from the Health Insurance Review and Assessment Service (HIRA) of Korea.

Results

During a median follow-up period of 3.23 years (95% CI: 3.14, 3.19), 88 subjects (2.02%) were newly diagnosed with hypoglycemia, and the incidence of hypoglycemia was 6.44 cases per 1,000 person-years (PY). Individuals with hypoglycemia were significantly older (59.7±10.7 vs. 53.3±10.4 years, p < 0.001), had more hospital visits (121.94±126.88 days/PY, p < 0.001), had a longer hospital stays (16.13±29.21 days/PY, p < 0.001), and incurred greater medical costs ($2,447.56±4,056.38 vs. $1,336.37±3,403.39 /PY, p < 0.001) than subjects without hypoglycemia.

Conclusion

Hypoglycemia-related events were infrequently identified among the medical records of T2DM subjects. However, they were associated significantly with poor clinical outcomes, and thus, hypoglycemia could have a substantial burden on the Korean national healthcare system.     

Assessment of Hemostasis after Plasma Exchange Using Rotational Thrombelastometry (ROTEM)

Background

Therapeutic plasma exchange (TPE)-based protocols immediately before cadaveric donor kidney transplantation have been extensively used in highly sensitized recipients. Plasma is generally preferred over human albumin as replacement fluid to avoid depletion of coagulation factors and perioperative bleeding. The aim of this study was to estimate bleeding risk after TPE replaced with albumin using rotational thromboelastography (ROTEM).

Methodology

Ten patients without overt coagulation abnormalities underwent TPE. Standard laboratory coagulation tests (thromboplastin time, activated partial thromboplastin time (aPTT), international normalized ratio (INR), thrombin clotting time, fibrinogen levels and antithrombin activity) were compared with thrombelastometry analysis (EXTEM and INTEM tests) before and after TPE.

Principal Findings

TPE significantly reduced fibrinogen levels (482 ± 182 vs. 223 ± 122 mg/dL), antithrombin activity (103 ± 11 vs. 54 ± 11 %), and prolonged aPTT (28 ± 3 vs. 45 ± 8 s), thromboplastin time (108 ± 11 vs. 68 ± 11 %), INR (0.95 ± 0.06 vs. 1.25 ± 0.16), and thrombin clotting time (18 ± 2 vs. 20 ± 3 s). INTEM and EXTEM analyses revealed significantly prolonged clot-formation time and reduced maximum clot firmness.

Conclusions/Significance

TPE replaced with albumin induces significant changes in global hemostasis parameters thus potentially increasing bleeding risk. Therefore, pretransplant TPE should be considered carefully in indicated patients before kidney transplantation. The role of the ROTEM point-of-care test to estimate the risk of bleeding in renal transplantation needs to be evaluated in further studies.     

Association between Hemoglobin Concentration and the Progression or Development of Albuminuria in Diabetic Kidney Disease

Aims

Anemia, which might contribute to pathogenesis of kidney dysfunction, is a common finding in patients with type 2 diabetes. The aim of this study was to investigate if hemoglobin concentration is associated with the degree of change in urinary albumin-creatinine ratio or the development of albuminuria in patients with type 2 diabetes.

Methods

We measured hemoglobin concentration in 470 (296 men and 174 women) consecutive type 2 diabetic patients without albuminuria. We performed a follow-up study to assess the progression or development of albuminuria, the interval of which was 3.0 years. Then we evaluated relationships between hemoglobin concentration and albuminuria, using multivariate linear regression analyses and logistic regression analyses.

Results

Eighty four patients developed albuminuria during follow-up duration. In multivariate analyses, hemoglobin concentration was negatively associated with a change in urinary albumin-creatinine ratio in men (ß = -0.259, P = 0.0002) and women (ß = -0.194, P = 0.030). Moreover, multivariate adjusted odds ratio associated with 1 g/L in hemoglobin for the development of albuminuria was 0.93 (95% confidence interval; 0.89-0.96) in men and 0.94 (95% confidence interval; 0.88-0.99) in women, respectively. And, multivariate analyses revealed that adjusted odds ratios for the development of albuminuria were 4.78 (95% confidence interval; 1.65-13.91) in men and 4.62 (95% confidence interval; 1.34-16.68) in women with anemia (hemoglobin < 130 g/L for men and < 120 g/L for women), which were higher than those without anemia.

Conclusions

Low hemoglobin concentration could be a predictor for the progression and development of albuminuria in patients with type 2 diabetes.     

Model for End-Stage Liver Disease (MELD) Score as a Predictor and Monitor of Mortality in Patients with Vibrio vulnificus Necrotizing Skin and Soft Tissue Infections

Background

Vibrio vulnificus necrotizing skin and soft tissue infections (VNSSTIs) usually predispose patients with or without preexisting liver disease to septic shock, and then evolve to multiple organ dysfunction syndrome (MODS), thus resulting in high mortality in humans. However, clinicians do not have a valid prediction model to provide a reliable estimate of case-fatality rate when caring for these acutely and/or critically ill patients.

Methods/Principal Findings

We retrospectively analyzed 39 consecutive patients with VNSSTIs (mean age: 65.7 ± 11.3 years) at our institution between 2007 and 2010. All patients were treated with the same protocol. Demographic and clinical characteristics, disease severity on admission, treatment details, and outcomes were collected for each patient and extracted for analyses. We studied the predictive value of the model for end-stage liver disease (MELD), modified MELD including sodium (MELD-Na), and laboratory risk indicator for necrotizing fasciitis (LRINEC) scores for case-fatality. Logistic regression and receiver operating characteristic (ROC) curve analyses were performed. The mean MELD, MELD-Na and LRINEC scores on admission were 15.1 ± 1.1, 17.7 ± 1.1, and 3.4 ± 0.4 points, respectively. After admission, these patients had temporary or progressive deterioration of nearly all their scores and lab values. The area under the ROC curve for the MELD and ΔMELD scoring models were 0.929 (p = 0.002) and 0.897 (p = 0.005), respectively. An optimal MELD/ΔMELD cutoff value ≥ 20/2 had a good sensitivity and specificity (all > 80%), with a 64/13-fold increased odds for case-fatality. Additionally, the development of severe forms of anemia (p = 0.014) and hypoalbuminemia (p = 0.019) were associated with an increased case-fatality rate.

Discussion

The MELD/ΔMELD scoring model is an effective risk stratification indicator at the time of admission and also an excellent condition monitor during hospitalization for medical care of acutely and/or critically ill patients with VNSSTIs.     

Comparison of the Dynesys Dynamic Stabilization System and Posterior Lumbar Interbody Fusion for Lumbar Degenerative Disease

Background

There have been few studies comparing the clinical and radiographic outcomes between the Dynesys dynamic stabilization system and posterior lumbar interbody fusion (PLIF). The objective of this study is to compare the clinical and radiographic outcomes of Dynesys and PLIF for lumbar degenerative disease.

Methods

Of 96 patients with lumbar degenerative disease included in this retrospectively analysis, 46 were treated with the Dynesys system and 50 underwent PLIF from July 2008 to March 2011. Clinical and radiographic outcomes were evaluated. We also evaluated the occurrence of radiographic and symptomatic adjacent segment degeneration (ASD).

Results

The mean follow-up time in the Dynesys group was 53.6 ± 5.3 months, while that in the PLIF group was 55.2 ± 6.8 months. At the final follow-up, the Oswestry disability index and visual analogue scale score were significantly improved in both groups. The range of motion (ROM) of stabilized segments in Dynesys group decreased from 7.1 ± 2.2° to 4.9 ± 2.2° (P < 0.05), while that of in PLIF group decreased from 7.3 ± 2.3° to 0° (P < 0.05). The ROM of the upper segments increased significantly in both groups at the final follow-up, the ROM was higher in the PLIF group. There were significantly more radiographic ASDs in the PLIF group than in the Dynesys group. The incidence of complications was comparable between groups.

Conclusions

Both Dynesys and PLIF can improve the clinical outcomes for lumbar degenerative disease. Compared to PLIF, Dynesys stabilization partially preserves the ROM of the stabilized segments, limits hypermobility in the upper adjacent segment, and may prevent the occurrence of ASD.