Functional Benefit after Modification of Radial Forearm Free Flap for Soft Palate Reconstruction

ObjectivesTo compare the velopharyngeal function, swallowing and speech of the conventional and modified radial forearm free flap (RFFF) for soft palate reconstruction.MethodsRetrospective clinical study. Twenty-eight patients who underwent oropharyngeal reconstruction with RFFF were divided into two groups: 10 patients had conventional folded RFFF and 18 patients underwent modified method.ResultsThe average speech intelligibility score in modified RFFF group was 8.0±2.4, and 6.2±2.2 in conventional RFFF group (P<0.05). The nasalance was 27.4±7.8% in modified group and 38.6±2.7% in conventional group during no nasal passage reading and 43.6±7.3% in modified group, 55.2±7.6% in conventional group during high nasal passage reading (P<0.05). The subjective swallowing functional score was 2.8 in modified group and 2.1 in conventional group.ConclusionThe speech assessment and nasalance demonstrate a more favorable outcome in modified group than conventional group

MN2006-17031 MEASUREMENT OF MECHANICAL STRENGTH OF NANO COMPOSITE FABRICATED BY NANO COMPOSITE DEPOSITION SYSTEM (NCDS)

ABSTRACT The rapid prototyping (RP) technology has been advanced for various applications such as verification of design, functional test. Recently, researchers have studied various materials to fabricate functional RP parts. In this research, a nano composite deposition system (NCDS), which can fabricate various nano composites using polymer resins with various nano particles, was introduced. The NCDS is a hybrid system in which material removal process by mechanical micro machining and/or the deposition process is combined. To predict the mechanical behavior of nano composite part made by NCDS, it is critical to understand the mechanical properties of the NCDS material. The NCDS process was characterizes by process parameters such as raster orientation, bead width, weight percent, and curing condition. Tensile strengths and compressive strengths of fabricated specimens with various raster orientation were measured, and various sample parts made of nano composites were fabricated using NCDS. INTRODUCTION The Rapid Prototyping technology has been advanced in product development cycle for more than 20 years. Relatively new approaches of RP cover micro scale devices such as micro-stereo lithography and various materials including ceramic and composite materials. Another promising area of RP application is bio and medical fields where simulation of operation by RP model is performed, and artificial bone made by RP is implanted into human body However, many RP machines still have the stair-step effect resulting in poor surface quality, time consuming post-process and limitation of applications for various materials. In this research, a nano composite deposition system (NCDS) was developed to fabricate three dimensional nano composite parts. The NCDS uses polymer resins as matrix and various nano particles to form composite materials, an

Novel IL-15 dendritic cells have a potent immunomodulatory effect in immunotherapy of multiple myeloma.

Dendritic cells (DCs) are the most potent antigen-presenting cells, and have thus been used in clinical cancer vaccines. However, the effects of DC vaccines are still limited, leading researchers to explore novel ways to make them effective. In this study, we investigated whether human monocyte-derived DCs generated via the addition of interleukin 15 (IL-15) had a higher capacity to induce antigen-specific T cells compared to conventional DCs. We isolated CD14+ monocytes from peripheral blood from multiple myeloma (MM) patients, and induced immature DCs with granulocyte-macrophage colony-stimulating factor (GM-CSF) and IL-4 in the presence or absence of IL-15 for 4-6 days. Then we generated mature DCs (mDCs) with lipopolysaccharide for another 2 days [IL-15 mDCs (6 days), IL-15 mDCs (8 days), and conventional mDCs (8 days)]. IL-15 mDCs (6 days) showed higher expression of MHC I and II, CD40, CD86, and CCR7, and the secretion of IFN-γ was significantly higher compared to conventional mDCs. IL-15 mDCs (6 days) showed superior polarization of naïve T cells toward Th1 cells and a higher proportion of activated T cells, cytokine-induced killer (CIK) cells, and natural killer (NK) cells for inducing strong cytotoxicity against myeloma cells, and lower proportion of regulatory T cells compared to conventional mDCs. These data imply that novel multipotent mDCs generated by the addition of IL-15, which can be cultivated in 6 days, resulted in outstanding activation of T cells, CIK cells and NK cells, and may facilitate cellular immunotherapy for cancer patients

Synergistic Antimyeloma Activity of Dendritic Cells and Pomalidomide in a Murine Myeloma Model

We have previously shown that immunization with tumor antigen-loaded dendritic cells (DCs) and the immunomodulating drug, lenalidomide, synergistically potentiates the enhancing antitumor immunity in a myeloma mouse model. In this study, we investigated the immunogenicity of DCs combined with pomalidomide and dexamethasone in a myeloma mouse model. MOPC-315 cells were injected subcutaneously to establish myeloma-bearing mice. Four test groups were used to mimic clinical protocol: (1) PBS control, (2) DCs, (3) pomalidomide + dexamethasone, and (4) DCs + pomalidomide + dexamethasone. The combination of DCs plus pomalidomide and dexamethasone displayed greater inhibition of tumor growth compared to the other groups. This effect was closely related with reduced numbers of immune suppressor cells including myeloid-derived suppressor cells, M2 macrophages, and regulatory T cells, with the induction of immune effector cells such as CD4+ and CD8+ T cells, memory T cells, natural killer (NK) cells, and M1 macrophages, and with the activation of T lymphocytes and NK cells in the spleen. Moreover, the level of the immunosuppressive factor vascular endothelial growth factor was significantly reduced in the tumor microenvironment. The collective findings in the murine myeloma model suggest that tumor antigen-loaded DCs combined with pomalidomide and dexamethasone synergistically enhance antitumor immunity by skewing the immune-suppressive status toward an immune-supportive status

Lenalidomide and Programmed Death-1 Blockade Synergistically Enhances the Effects of Dendritic Cell Vaccination in a Model of Murine Myeloma

The therapeutic efficacy of dendritic cell (DC)-based immunotherapy may be potentiated in combination with other anticancer therapies that enhance DC function by modulating immune responses and the tumor microenvironment. In this study, we investigated the efficacy of DC vaccination in combination with lenalidomide and programmed death (PD)-1 blockade in a model of murine myeloma. MOPC-315 cell lines were injected subcutaneously to establish myeloma-bearing mice and the following five test groups were established: PBS control, DCs, DCs + lenalidomide, DCs + PD-1 blockade, and DCs + lenalidomide + PD-1 blockade. The combination of DCs plus lenalidomide and PD-1 blockade more potently inhibited tumor growth compared to the other groups. This effect was associated with a reduction in immune suppressor cells (such as myeloid-derived suppressor cells, M2 macrophages, and regulatory T cells) and an increase in immune effector cells [such as CD4+ and CD8+ T cells, natural killer (NK) cells, and M1 macrophages] in the spleen. Functional activities of cytotoxic T lymphocytes and NK cells were also enhanced by the triple combination. Levels of immunosuppressive cytokines, such as TGF-β and IL-10, were significantly reduced in the tumor microenvironment. These findings suggest that the combination of DCs plus lenalidomide and PD-1 blockade synergistically establishes a robust anti-myeloma immunity through a two-way mechanism, which inhibits immunosuppressive cells while activating effector cells with superior polarization of the Th1/Th2 balance in favor of the tumor immune response. This result should provide an experimental ground for incorporating check point inhibitors to existing immunotherapeutic modalities against multiple myeloma

Expanded natural killer cells potentiate the antimyeloma activity of daratumumab, lenalidomide, and dexamethasone in a myeloma xenograft model.

The development of new treatment agents in recent decades has significantly improved the survival of patients with multiple myeloma (MM). Nonetheless, MM remains an incurable disease; therefore, novel combination therapies are required. Natural killer (NK) cells are one of the safest immunotherapeutic options. In this study, we found that the anti-myeloma activity of expanded NK cells (eNKs) was improved by daratumumab, lenalidomide, and dexamethasone (DRd) in an MM xenograft mouse model. NK cells expanded from peripheral blood mononuclear cells collected from MM patients were highly cytotoxic against DRd pretreated tumor cells in vitro. To mimic the clinical protocol, a human MM xenograft model was developed using human RPMI8226-RFP-FLuc cells in NOD/SCID IL-2Rγnull (NSG) mice. MM bearing mice were randomly divided into six groups: no treatment, eNK, Rd, Rd + eNKs, DRd, and DRd + eNKs. DRd significantly enhanced the cytotoxicity of eNKs by upregulating NK cell activation ligands and effector function. DRd in combination with eNKs significantly reduced the serum M-protein level and prolonged mouse survival. In addition, DRd significantly increased the persistence of eNK and homing to MM sites. These results show that the anti-myeloma activity of ex vivo-expanded and activated NK cells is augmented by the immunomodulatory effect of DRd in MM-bearing mice, suggesting the therapeutic potential of this combination for MM patients

Association between Obesity and Physical Fitness, and Hemoglobin A1c Level and Metabolic Syndrome in Korean Adults

BACKGROUND: The purpose of the current study was to investigate the association of obesity level, physical fitness level, hemoglobin A1c (HbA1c) level and metabolic syndrome (MetS) risk factors among Korean adults. METHODS: A total of 557 adults (272 males and 285 females) who underwent medical check-up at local hospital were recruited. In addition to regular health check-up, cardiopulmonary fitness, muscular endurance were measured and their association were analyzed. RESULTS: The prevalence of MetS was 31.7% for males and 23.7% for females. Females with the higher muscular endurance had lower waist circumference, triglyceride level, and HbA1c level than those with the lower muscular endurance. Males with the higher level of cardiopulmonary fitness had lower diastolic blood pressure, lower high-sensitivity C-reactive protein level and higher high density lipoprotein cholesterol level than males with the lower level of cardiopulmonary fitness. Females with the higher level of cardiopulmonary fitness had lower body weight, body mass index, systolic blood pressure, and fasting blood glucose level than females with the lower level of cardiopulmonary fitness. Participants with the higher level of adiposity and the lower level of physical fitness were 5.26 times (95% confidence interval [CI], 2.19 to 12.62), 5.71 times (95% CI, 2.23 to 14.60) more likely to have MetS, respectively, in male and female compared to participants who were neither obese nor have the lower level of fitness. CONCLUSION: This study suggests that maintaining a healthy body weight as well as a certain level of fitness is important for the prevention of MetS.ope

Expansion of cytotoxic natural killer cells in multiple myeloma patients using K562 cells expressing OX40 ligand and membrane-bound IL-18 and IL-21.

BACKGROUND: Natural killer (NK) cell-based immunotherapy is a promising treatment approach for multiple myeloma (MM), but obtaining a sufficient number of activated NK cells remains challenging. Here, we report an improved method to generate ex vivo expanded NK (eNK) cells from MM patients based on genetic engineering of K562 cells to express OX40 ligand and membrane-bound (mb) IL-18 and IL-21. METHODS: K562-OX40L-mbIL-18/-21 cells were generated by transducing K562-OX40L cells with a lentiviral vector encoding mbIL-18 and mbIL-21, and these were used as feeder cells to expand NK cells from peripheral blood mononuclear cells of healthy donors (HDs) and MM patients in the presence of IL-2/IL-15. Purity, expansion rate, receptor expression, and functions of eNK cells were determined over four weeks of culture. RESULTS: NK cell expansion was enhanced by short exposure of soluble IL-18 and IL-21 with K562-OX40L cells. Co-culture of NK cells with K562-OX40L-mbIL-18/-21 cells resulted in remarkable expansion of NK cells from HDs (9,860-fold) and MM patients (4,929-fold) over the 28-day culture period. Moreover, eNK cells showed increased expression of major activation markers and enhanced cytotoxicity towards target K562, U266, and RPMI8226 cells. CONCLUSIONS: Our data suggest that genetically engineered K562 cells expressing OX40L, mbIL-18, and mbIL-21 improve the expansion of NK cells, increase activation signals, and enhance their cytolytic activity towards MM cells

Percutaneous nephrostomy for nondilated renal collecting system with ultrasound and fluoroscopic guidance: The results of a 10-year experience

PURPOSEThis study aimed to evaluate the technical success rate, complications, and radiation doses of ultrasound- and fluoroscopy-guided percutaneous nephrostomy (PCN) in patients with a nondi- lated renal collecting system.METHODSOver a 10-year period, 50 patients were referred for PCN of 60 kidneys with a nondilated renal collecting system. The patients included 22 males and 28 females with a mean age of 63.2 years (range: 35-87 years). The most common reason for PCN in these patients was postoperative ure- teral leaks and/or fistula (21/50 patients). PCN was performed under ultrasound and fluoroscopic guidance. During PCN, intravenous contrast media or diuretics were not used. Technical success rate, complications, procedure time, and radiation exposure of the procedure were retrospec- tively evaluated.RESULTSUltrasound- and fluoroscopy-guided PCN for nondilated renal collecting system showed a suc- cess rate of 83.3% (50/60 kidneys) in the initial attempt. Four PCNs were repeated and were suc- cessful after the initial PCN failure. There was 1 major complication of bleeding that required transfusion in 1.9% (1/54) PCNs and there were minor complications of transient gross hematuria through the PCN catheter in 31.5% (17/54) PCNs. Mean duration of the procedure was 15.97 ± 7.81 min and median fluoroscopy time was 4.2 min (range: 1.2-15.3 min). Median dose area product and cumulative dose were 345.37 μGy·m2 (range: 42.57-1659.76 μGy·m2) and 46.9 mGy (range: 7.7-267.8 mGy), respectively.CONCLUSIONUltrasound- and fluoroscopy-guided PCN for nondilated renal collecting system was feasible with acceptable technical success rate, complication rate, procedure time, and radiation exposure

High dose therapy followed by autologous peripheral blood stem cell transplantation as a first line treatment for multiple myeloma: a Korean Multicenter Study.

We conducted a phase II multicenter trial to estimate the response and survival of patients with newly diagnosed multiple myeloma to high dose melphalan therapy followed by autologous peripheral blood stem cell transplantation. Eligible patients who had undergone induction with vincristine, adriamycin and dexamethasone (VAD) should have adequate cardiac, pulmonary and renal function (creatinine <2 mg/dL). Melphalan at 200 mg/m2 was used as a conditioning regimen. Eighty patients were enrolled from 13 centers. The median age of the patients was 53 yr (range; 20 to 68 yr). The initial stage was IA/IIA/IIB/IIIA/IIIB in 3/8/1/54/14 patients, respectively. Beta2-microglobulin, CRP and LDH were increased in 74, 42 and 34% of the patients examined. Cytogenetic data were available in 30 patients, and 6 patients showed numeric or structural abnormalities. Two therapy-related mortalities occurred from infection. Among the 78 evaluable patients, CR/PR/MR/NC/PD were achieved in 48/26/2/1/1 patients, respectively. After a median follow-up of 30 months, the median overall and event-free survivals were 66 months (95% CI: 20-112) and 24 months (95% CI: 18-29), respectively. This study verifies the efficacy and feasibility of high dose melphalan therapy with autologous stem cell transplantation in newly diagnosed multiple myeloma