Electrosprayable Levan-Coated Nanoclusters and Ultrasound-Responsive Drug Delivery for Cancer Therapy.

In this study, we synthesized levan shell hydrophobic silica nanoclusters encapsulating doxorubicin (L-HSi-Dox) and evaluated their potential as ultrasound-responsive drug delivery systems for cancer treatment. L-HSi-Dox nanoclusters were successfully fabricated by integrating a hydrophobic silica nanoparticle-doxorubicin complex as the core and an amphiphilic levan carbohydrate polymer as the shell by using an electrospray technique. Characterization analyses confirmed the stability, size, and composition of the nanoclusters. In particular, the nanoclusters exhibited a controlled release of Dox under aqueous conditions, demonstrating their potential as efficient drug carriers. The levanic groups of the nanoclusters enhanced the targeted delivery of Dox to specific cancer cells. Furthermore, the synergism between the nanoclusters and ultrasound effectively reduced cell viability and induced cell death, particularly in the GLUT5-overexpressing MDA-MB-231 cells. In a tumor xenograft mouse model, treatment with the nanoclusters and ultrasound significantly reduced the tumor volume and weight without affecting the body weight. Collectively, these results highlight the potential of the L-HSi-Dox nanoclusters and ultrasound as promising drug delivery systems with an enhanced therapeutic efficacy for biomedical applications.

Actively cross-linking hemostatic sealant enables rapid hemostasis and wound closure.

A rapid hemostatic sealant can save a patient's life from shock and death due to severe trauma or excessive bleeding from the wound site during surgery. However, an ideal hemostatic sealant needs to meet the standards of safety, efficacy, usability, cost, and approvability and overcome new challenges. Here, we devised a combinatorial hemostatic sealant of PEG succinimidyl glutarate-based cross-linking branched polymers (CBPs) and the active hemostatic peptide (AHP). After ex vivo optimization, the best hemostatic combination was called an active cross-linking hemostatic sealant (ACHS). Interestingly, ACHS formed cross-links with serum proteins, blood cells, and tissue and interconnected coating on blood cells, which might induce hemostasis and tissue adhesion based on SEM images. Moreover, ACHS showed the highest coagulation efficacy, formation, and agglomeration of thrombi within 12 s, and in vitro biocompatibility. Mouse model experiments represented rapid hemostasis within 1 min, wound closure of the liver incision, and less bleeding than the commercialized sealant with tissue biocompatibility. ACHS has the advantages of rapid hemostasis, mild sealant, and easy supply by chemical synthesis without inhibition by anticoagulants, which might minimize bacterial infection by immediate wound closure. Therefore, ACHS could become a new-type hemostatic sealant to match surgical needs for internal bleeding.

Gamma-glutamyltransferase and the risk of head and neck cancer mortality.

BACKGROUND: The purpose of this study was to determine the association between baseline serum gamma-glutamyltransferase levels and the mortality risk of head and neck cancers. METHODS: A total of 481 414 Korean participants aged 40-79 years at enrollment were examined. The hazard ratios for head and neck cancer mortality were analyzed using Cox proportional hazards models, which were adjusted for potential confounding factors. RESULTS: In the overall study population, high gamma-glutamyltransferase levels were significantly associated with head and neck cancers mortality in a dose-response linear relation (p < 0.001). After excluding participants (n = 125) who died of head and neck cancers within five years of enrollment, the main results remained similar to those of the analysis of all 313 head and neck cancers deaths in the study population. CONCLUSION: These findings indicate that serum gamma-glutamyltransferase activity is positively associated with an increased mortality risk in head and neck cancers in a dose-dependent manner.

Risk factors of head and neck cancer mortality compared with those of all-cause and all-cancer mortalities.

This study aimed to clarify the risk factors of head and neck cancer (HNC) mortality, relative to those of all-cause and all-cancer mortalities, using the Korean National Health Insurance Service-Health Screening Cohort (NHIS-HEALS) data set. Data from 238 HNC deaths, 14,769 all-cancer deaths, and 38,086 all-cause deaths were extracted during a median follow-up period of 9.5 years. Baseline characteristics were assessed via chi-square tests, t tests, and multivariable logistic regression. HNC mortality was found to be positively associated with male sex, past and current smoking habits, moderate-to-heavy alcohol consumption, and being underweight. In addition, serum gamma-glutamyltransferase level was found to be significantly elevated in cases of HNC mortality. In contrast, obesity, a history of diabetes, and fasting blood glucose levels were found to be inversely associated with overall HNC mortality. Among the HNC subtypes, mortality due to laryngeal cancer was most strongly associated with past and heavy cigarette smoking, and mortality due to oro-/hypopharyngeal cancer was most strongly associated with heavy alcohol consumption. The present study demonstrates that this nationwide, population-based NHIS-HEALS data set can provide useful information for health research and policy development.

The supraclavicular artery island flap: a salvage option for head and neck reconstruction.

BACKGROUND: Some of head and neck cancer patients are in compromised general condition after ablation surgery and chemoradiation therapy, which makes secondary free tissue transfer quite challenging. Elderly cancer patients also have some risk for microvascular surgery with lengthened general anesthesia. In those cases, the pedicled flap vascularized by supraclavicular artery could be considered as an alternative to free flap. Despite several authors have demonstrated the clinical reliability of supraclavicular artery island flap (SCAIF), to date, SCAIF has not been widely used among reconstructive surgeon. In this article, we clarified vascular flow pattern and introduce simple surgical technique of SCAIF with a literature review. CASE PRESENTATION: Three patients who had underwent previous neck surgery and adjuvant therapy received maxillofacial reconstruction using SCAIF. It required only a few landmarks, flap harvesting was carried out, and the elapsed time gradually decreased to 15 min with experiences. There were no remarkable morbidities in both donor and recipient sites. CONCLUSION: SCAIF exhibited minimal anatomic variations and short learning curve of surgical techniques, which might be valuable reconstruction modality for beginning surgeon. And it can be beneficial option for the patients with vessel-depleted neck, medically compromised status for lengthened general anesthesia and failed free tissue transfer.

Flap necrosis after palatoplasty in irradiated patient and its reconstruction with tunnelized-facial artery myomucosal island flap.

BACKGROUND: Tunneled transposition of the facial artery myomucosal (FAMM) island flap on the lingual side of the mandible has been reported for intraoral as well as oropharyngeal reconstruction. This modified technique overcomes the limitations of short range and dentition and further confirms the flexibility of the flap. This paper presents a case of reconstructing secondary soft palatal defect due to flap necrosis following two-flap palatoplasty in irradiated patient with lingually transposed facial artery myomucosal island flap. CASE PRESENTATION: The authors successfully reconstructed secondary soft palatal defect due to flap necrosis following two-flap palatoplasty in an irradiated 59-year-old female patient with tunnelized-facial artery myomucosal island flap (t-FAMMIF). CONCLUSIONS: Islanding and tunneling modification extends the versatility of the FAMM flap in the reconstruction of soft palatal defects post tumor excision and even after radiation, giving a great range of rotation and eliminating the need for revision in a second stage procedure. The authors thus highly recommend this versatile flap for the reconstruction of small and medium-sized oral defects.

Multiple Oral Deep Penetrating Nevi Extending to the Masseter and Buccal Fat Pad.

The deep penetrating nevus (DPN) is a rare benign melanocytic tumor often clinically and histopathologically mistaken for malignant melanoma (MM) and other nevus types. This report describes an extremely rare case of multiple lesions of a large DPN in the oral cavity with extensive infiltration to the minor salivary gland, buccal fat pad, buccinators, and masseter muscles, yet with preservation of the normal anatomic architecture. After receiving a diagnosis of MM in another hospital, the patient was at risk for receiving a wide excision that included the masticatory muscles, facial nerve, and overlying skin. Histopathologically, distinct cellular properties were completely masked with heavy pigmentation, thus precluding a proper distinction of benignity versus malignancy. The proliferative capacity of the tumor was analyzed further by immunohistochemistry of bleached tissue sections and tumor behavior was indirectly evaluated by insufficient tumor stromal interaction, with the conclusion that the specimen was benign. Conservative surgery was limited to the oral cavity. Multiple DPNs in the oral cavity merit attention because of the high risk of being mistaken for MM, which would require a wider surgical excision of the head and neck region.

Combined Effect of Blood Cadmium and Lead Levels on Coronary Heart Disease Prediction Risk in Korean Men.

This study was designed to investigate the combined effects of cadmium (Cd) and lead (Pb) on 10-year coronary heart disease (CHD) risk calculated using the Framingham risk score. The heavy metal data set of the Korean National Health and Nutrition Examination Survey IV and V (2008-2010) was analyzed. The 10-year CHD risk was significantly associated with the log-transformed blood Cd and Pb levels in Korean men. For the highest quartile of Cd and Pb, the odds ratio (OR) of the intermediate risk and beyond for CHD (10-year risk ≥10%) compared to the lowest quartile was 6.870 (Cd, 95% confidence interval [CI]: 4.58-10.30) and 3.127 (Pb, 95% CI: 2.09-4.69) after adjusting for confounders, respectively. The adjusted OR of the intermediate risk and beyond for CHD (10-year risk ≥10%) in the fourth quartile of both Cd and Pb was 12.2 (95% CI: 8.0-18.5) compared to the reference group (first and second quartiles of Cd and Pb). However, the association between log-transformed blood Cd and Pb and the 10-year CHD risk was not significant in Korean women.

Association between Fibrinogen and Carotid Atherosclerosis According to Smoking Status in a Korean Male Population.

PURPOSE: Although inconsistent, reports have shown fibrinogen levels to be associated with atherosclerosis. Accordingly, since cigarette smoking is associated with increased levels of fibrinogen and atherosclerosis, it may also affect the association between fibrinogen and atherosclerosis. We investigated the associations between fibrinogen and carotid intima-media thickness (IMT) according to smoking status in a Korean male population. MATERIALS AND METHODS: Plasma fibrinogen levels were measured in 277 men aged 40-87 years without a history of myocardial infarction or stroke. High-resolution B-mode ultrasonography was used to examine the common carotid arteries. IMT level was analyzed both as a continuous (IMT-max, maximum value; IMT-tpm, 3-point mean value) and categorical variable (higher IMT; presence of plaque). Serial linear and logistic regression models were employed to examine the association between fibrinogen and IMT according to smoking status. RESULTS: Fibrinogen levels were positively associated with IMT-max (standardized ß=0.25, p=0.021) and IMT-tpm (standardized ß=0.21, p=0.038), even after adjusting for age, body mass index, systolic blood pressure, fasting glucose, and total cholesterol to high-density lipoprotein cholesterol ratio in current smokers (n=75). No significant association between fibrinogen and IMT, however, was noted in former smokers (n=80) or nonsmokers (n=122). Adjusted odds ratios (95% confidence interval) for having plaque per one standard deviation higher fibrinogen level were 2.06 (1.09-3.89) for current smokers, 0.68 (0.43-1.10) for former smokers, and 1.06 (0.60-1.87) for nonsmokers. CONCLUSION: Our findings suggest that cigarette smoking may modify the association between fibrinogen and carotid atherosclerosis. Further studies are required to confirm this finding in different populations.

Differences in the Survival of Gastric Cancer Patients after Gastrectomy according to the Medical Insurance Status.

PURPOSE: In Korea, the entire population must enroll in the national health insurance system, and those who are classified as having a lower socioeconomic status are supported by the medical aid system. The aim of this study was to evaluate the association of the medical insurance status of gastric cancer patients with their survival after gastrectomy. MATERIALS AND METHODS: A total of 247 patients who underwent surgical treatment for gastric cancer between January 1999 and December 2010 at the Seoul Medical Center were evaluated. Based on their medical insurance status, the patients were classified into two groups: the national health insurance registered group (n=183), and the medical aid covered group (n=64). The survival rates were calculated using the Kaplan-Meier method. RESULTS: The median postoperative duration of hospitalization was longer in the medical aid covered group and postoperative morbidity and mortality were higher in the medical aid group than in the national health insurance registered group (P<0.05). The overall 5-year survival rate was 43.9% in the medical aid covered group and 64.3% in the national health insurance registered group (P=0.001). CONCLUSIONS: The medical insurance status reflects the socioeconomic status of a patient and can influence the overall survival of gastric cancer patients. A more sophisticated analysis of the difference in the survival time between gastric cancer patients based on their socioeconomic status is necessary.

Association between serum uric acid level and metabolic syndrome.

OBJECTIVES: Serum uric acid levels have been reported to be associated with a variety of cardiovascular conditions. However, the direct association between uric acid levels and metabolic syndrome remains controversial. Thus, we evaluated the association of serum uric acid levels and metabolic syndrome in a community-based cohort study in Korea. METHODS: We performed cross-sectional analysis of baseline data of 889 males and 1491 females (aged 38 to 87) who participated in baseline examinations of the Korean Genome and Epidemiology Study: Kanghwa study. Blood samples were collected after at least an 8 hour fast. Uric acid quartiles were defined as follows: <4.8, 4.8-<5.6, 5.6-<6.5, ≥6.5 mg/dL in males; and <3.8, 3.8-<4.3, 4.3-<5.1, ≥5.1 mg/dL in females. Metabolic syndrome was defined by the National Cholesterol Education Program Adult Treatment Panel III Criteria with adjusted waist circumference cutoffs (90 cm for males; 80 cm for females). The association between serum uric acid quartiles and metabolic syndrome was assessed using multivariate logistic regression. RESULTS: The odds ratio for having metabolic syndrome in the highest versus lowest quartiles of serum uric acid levels was 2.67 (95% confidence interval [CI], 1.60 to 4.46) in males and 2.14 (95% CI, 1.50 to 3.05) in females after adjusting for age, smoking, alcohol intake, body mass index, total cholesterol, HbA1c, albumin, γ-glutamyltransferase, blood urea nitrogen, and log C-reactive protein. The number of metabolic abnormalities also increased gradually with increasing serum uric acid levels (adjusted p for trend < 0.001 in both sexes). CONCLUSIONS: Higher serum uric acid levels are positively associated with the presence of metabolic syndrome in Korean males and females.

The association between serum albumin levels and metabolic syndrome in a rural population of Korea.

OBJECTIVES: A positive association between serum albumin levels and metabolic syndrome has been reported in observation studies, but it has not been established in the Korean population. The purpose of this study was to evaluate the association between serum albumin levels and the presence of metabolic syndrome among a sample of apparently healthy Korean adults. METHODS: This cross-sectional study analyzed data of 3189 community-dwelling people (1189 men and 2000 women) who were aged 40 to 87 years and were living in a rural area in Korea. Serum albumin levels were classified into quartile groups for each sex. Metabolic syndrome was defined according to the National Cholesterol Education Program Adult Treatment Panel III guidelines with an adjusted waist circumference cut-off value (≥90 cm for men and ≥85 cm for women). An independent association between serum albumin levels and metabolic syndrome was assessed by multiple logistic regression analysis. RESULTS: Higher serum albumin levels were associated with increased prevalence of metabolic syndrome. The odds ratio (95% confidence interval) of the prevalence of metabolic syndrome for the highest versus the lowest serum albumin quartiles was 2.81 (1.91 to 4.14) in men and 1.96 (1.52 to 2.52) in women, after adjusting for age, smoking status, alcohol consumption, and physical activity. When each metabolic abnormality was analyzed separately, higher serum albumin levels were significantly associated with hypertriglyceridemia and hyperglycemia in both sexes, and with abdominal obesity in men. CONCLUSIONS: These results suggest that higher serum albumin levels are positively associated with an increased risk of metabolic syndrome in Korean adults.