The Trends and Outcomes of Initial Palliative Chemotherapy in Patients with Pancreatic Cancer in Korea Based on National Health Insurance Service Data.

Background/Objectives: The survival rate of patients with pancreatic cancer (PC) has improved gradually since the introduction of FOLFIRINOX (FFX) and gemcitabine + albumin-bound paclitaxel (GnP) regimens. However, the trends and outcomes of initial palliative chemotherapy before and after the advent of these regimens and their contribution to survival rates are not well understood. This study aimed to investigate this in patients with PC in Korea using claims data from the National Health Insurance Service (NHIS). Methods: Patients diagnosed with PC who underwent initial palliative chemotherapy between 2007 and 2019 were identified from the NHIS database. Patient demographics, comorbidities, chemotherapy regimens, and survival rates were analyzed using follow-up data up to 2020. Results: In total, 14,760 patients (mean age, 63.78 ± 10.18 years; men, 59.19%) were enrolled. As initial palliative chemotherapy, 3823 patients (25.90%) received gemcitabine alone; 2779 (18.83%) received gemcitabine + erlotinib; 1948 (13.20%) received FFX; and 1767 (11.97%) received GnP. The median survival values were 15.00 months for FFX; 11.04 months for GnP; 8.40 months for gemcitabine alone; and 8.51 months for gemcitabine + erlotinib. The adjusted hazard ratio (aHR) for GnP vs. FFX was 1.291 (95% CI, 1.206-1.383) in the multivariate Cox regression analysis of mortality. Radiation therapy (aHR, 0.667; 95% CI, 0.612-0.728) and second-line chemotherapy (aHR, 0.639; 95% CI, 0.597-0.684) were significantly associated with improved survival. Conclusions: Our study found that first-line chemotherapy with FFX was associated with significantly longer survival than the other regimens, although caution is needed in interpreting the results.

Risk of Subsequent Primary Cancers in Thyroid Cancer Survivors according to the Dose of Levothyroxine: A Nationwide Cohort Study.

BACKGRUOUND: Current research has not investigated the effect of thyroid-stimulating hormone suppression therapy with levothyroxine on the risk for developing subsequent primary cancers (SPCs). This study aimed to investigate the association between levothyroxine dosage and the risk for SPCs in thyroid cancer patients. METHODS: We conducted a nationwide population-based retrospective cohort study form Korean National Health Insurance database. This cohort included 342,920 thyroid cancer patients between 2004 and 2018. Patients were divided into the non-levothyroxine and the levothyroxine groups, the latter consisting of four dosage subgroups according to quartiles. Cox proportional hazard models were performed to evaluate the risk for SPCs by adjusting for variables including cumulative doses of radioactive iodine (RAI) therapy. RESULTS: A total of 17,410 SPC cases were observed over a median 7.3 years of follow-up. The high-dose levothyroxine subgroups (Q3 and Q4) had a higher risk for SPC (adjusted hazard ratio [HR], 1.14 and 1.27; 95% confidence interval [CI], 1.05-1.24 and 1.17- 1.37; respectively) compared to the non-levothyroxine group. In particular, the adjusted HR of stomach (1.31), colorectal (1.60), liver and biliary tract (1.95), and pancreatic (2.48) cancers were increased in the Q4 subgroup. We consistently observed a positive association between high levothyroxine dosage per body weight and risk of SPCs, even after adjusting for various confounding variables. Moreover, similar results were identified in the stratified analyses according to thyroidectomy type and RAI therapy, as well as in a subgroup analysis of patients with good adherence. CONCLUSION: High-dose levothyroxine use was associated with increased risk of SPCs among thyroid cancer patients regardless of RAI therapy.

Second Primary Malignancy After Radioiodine Therapy in Thyroid Cancer Patient: A Nationwide Study.

Objective: This study aimed to investigate the risk of second primary malignancy after radioiodine (RAI) therapy in patients with thyroid cancer, using the National Health Insurance Service (NHIS) database. Methods: We extracted data from the NHIS database of South Korea, which covers the entire population of the nation. Risk of second primary malignancy in the thyroid cancer patients who received RAI therapy were compared with the thyroid cancer patients who received surgery only. Results: Between January 1, 2004, and December 31, 2018, we identified 363,155 patients who underwent thyroid surgery due to thyroid cancer for analysis. The surgery only cohort was 215,481, and the RAI cohort was 147,674 patients. A total of 19,385 patients developed second primary malignancy (solid cancer, 18,285; hematologic cancer, 1,100). There was no significant increase in the risk of second primary malignancy in patients who received a total cumulative dose of 100 mCi or less (hazard ratio [HR], 1.013; 95% confidence interval [CI], 0.979-1.049). However, a statistically significant increase in the risk of second primary malignancy was observed in patients who received 101-200 mCi (HR, 1.214; 95% CI, 1.167-1.264), 201-300 mCi (HR, 1.422; 95% CI, 1.258-1.607), and > 300 mCi (HR, 1.693; 95% CI, 1.545-1.854). Conclusion: Total cumulative doses of 100 mCi or less of RAI can be safely administered without concerns about second primary malignancy. However, the risk of second primary malignancy increases in a dose-dependent manner, and the risk-benefit needs to be considered for doses over 100 mCi of RAI therapy.

Nipple Reconstruction Using the Semilunar Flap and Omega-shaped Acellular Dermal Matrix Strut.

BACKGROUND: Various operative methods exist for nipple reconstruction. Selection of an appropriate skin flap and core strut material is imperative in achieving a satisfactory outcome in nipple reconstruction. Long-term maintenance of nipple projection requires further investigation by surgeons. We propose a new technique that uses a semilunar flap and omega-shaped acellular dermal matrix (ADM). METHODS: Total 53 nipples were reconstructed by this method. An omega-shaped ADM strut was inserted into the barrel made by a semilunar flap. The footplates of omega-shaped ADM struts were spread out under the subcutaneous tissue of the donor site of the semilunar flap to support the dome of the omega strut. RESULTS: The mean maintenance rate of nipple projection was 95.12 ± 6.30% at 3 weeks, 80.60 ± 8.93% at 3 months, and 71.70 ± 8.67% at 6 months postoperatively when compared to the projection observed in the immediate postoperative period. Thirty-five patients (66.0%) showed a maintenance rate over 70% at 6 months post operation, with most patients (94.3%) demonstrating a maintenance rate greater than 60%. CONCLUSIONS: Our study with the omega-shaped ADM strut showed superior maintenance rates of projection when compared to other studies on that used AlloDerm® as a core strut for nipple reconstruction. Omega-shaped struts, when made with cross-linked thick ADM, supported the skin flap quite well. We propose that our method combining the semilunar flap with an omega-shaped ADM may be a good option for nipple reconstruction. LEVEL OF EVIDENCE IV: "This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors   www.springer.com/00266 ."

Comparative Interrupted Time Series Analysis of Long-term Direct Medical Costs in Patients With Hip Fractures and a Matched Cohort: A Large-database Study.

BACKGROUND: Previous studies on medical costs in patients with hip fractures have focused on medical costs incurred for a short period after the injury. However, patients often had comorbidities before their hip fractures that would have affected medical costs even had they not sustained a fracture. Consequently, these studies may have overestimated the costs associated with hip fractures and did not characterize the duration of increased medical costs adequately. Without knowing this crucial information, it is difficult to craft thoughtful health policy to support these patients' needs. QUESTIONS/PURPOSES: (1) To compare the direct medical costs for 5 years before fracture and up to 5 years after injury in a group of patients who underwent hip fracture surgery with a matched group of patients who did not experience a hip fracture, (2) to analyze the duration over which the increased direct medical costs associated with a hip fracture continues, and (3) to analyze whether there is a difference in direct medical costs according to age group using a nationwide claims database in South Korea. METHODS: The National Health Insurance Service Sample cohort in South Korea consisted of 1 million patients who were selected using a systematic, stratified, random sampling method from 48,222,537 individuals on December 31, 2006. Under a compulsory social insurance system established by the National Health Insurance Act, all patients were followed until 2015. Patients with hip fractures and matched controls were selected from the National Health Insurance Service sample of South Korea. Patients with hip fractures were defined as those who were hospitalized with a diagnosis of femoral neck fracture or intertrochanteric fracture and who underwent surgical treatment. We excluded patients with hip fractures before January 1, 2007 to ensure a minimum 5-year period that was free of hip fractures. Patients with hip fractures were matched with patients of the same age and gender at the date of admission to an acute care hospital for surgery (time zero). If patients with hip fractures died during the follow-up period, we performed matching among patients whose difference from the time of death was within 1 month. This method of risk-set matching was repeated sequentially for the next patient until the last patient with a hip fracture was matched. We then sequentially performed 1:5 random sampling for each risk set. A total of 3583 patients in the hip fracture cohort (patients with hip fractures) and 17,915 patients in the matched cohort (those without hip fractures) were included in this study. The mean age was 76 ± 9 years, and 70% were women in both groups. Based on the Charlson comorbidity index score, medication, and medical history, the patients with hip fractures had more comorbidities. Person-level direct medical costs per quarter were calculated for 5 years before time zero and up to 5 years after time zero. Direct medical costs were defined as the sum of that insurer's payments (that is, the National Health Insurance Service's payments), and that patient's copayments, excluding uncovered payments. We compared direct medical costs between patients with hip fractures and the patients in the matched cohort using a comparative interrupted time series analysis. The difference-in-difference estimate is the ratio of the differences in direct medical costs before and after time zero in the hip fracture cohort to the difference in direct medical costs before and after time zero in the matched cohort; the difference in difference estimates were calculated each year after injury. To identify changes in direct medical cost trends in patients with hip fractures and all subgroups, joinpoint regression was estimated using statistical software. RESULTS: The direct medical costs for the patients with hip fractures were higher than those for patients in the matched cohort at every year during the observation period. The difference in direct medical costs between the groups before time zero has increased every year. The direct medical costs in patients with hip fractures was the highest in the first quarter after time zero. Considering the differential changes in direct medical costs before and after time zero, hip fractures incurred additional direct medical costs of USD 2514 (95% CI 2423 to 2606; p < 0.01) per patient and USD 264 (95% CI 166 to 361; p < 0.01) per patient in the first and second years, respectively. The increase in direct medical costs attributable to hip fracture was observed for 1.5 to 2 years (difference-in-difference estimate at 1 year 3.0 [95% CI 2.8 to 3.2]; p < 0.01) (difference-in-difference estimate at 2 years 1.2 [95% CI 1.1 to 1.3]; p < 0.01; joinpoint 1.5 year). In the subgroups of patients younger than 65, patients between 65 and 85, and patients older than 85 years of age, the increase in direct medical costs attributable to hip fracture continued up to 1 year (difference-in-difference estimate ratio at 1 year 2.7 [95% CI 2.1 to 3.4]; p < 0.01; joinpoint 1 year), 1.5 to 2 years (difference-in-difference estimate ratio at 1 year 2.8 [95% CI 2.6 to 3.1]; p < 0.01; difference-in-difference estimate ratio at 2 years 1.2 [95% CI 1.1 to 1.3]; p < 0.01; joinpoint 1.5 years), and 39 months to 5 years (difference-in-difference estimate ratio at 1 year 5.2 [95% CI 4.4 to 6.2]; p < 0.01; difference-in-difference estimate ratio at 5 years 2.1 [95% CI 1.4 to 3.1]; p < 0.01; joinpoint 39 months) from time zero, respectively. CONCLUSION: The direct medical costs in patients with hip fractures were higher than those in the matched cohort every year during the 5 years before and after hip fracture. The increase in direct medical costs because of hip fractures was maintained for 1.5 to 2 years and was greater in older patients. Based on this, we suggest that health policies should focus on patients' financial and social needs, with particular emphasis on the first 2 years after hip fracture with stratification based on patients' ages. LEVEL OF EVIDENCE: Level II, economic analysis.

Effect of Helicobacter pylori Treatment on Long-term Mortality in Patients with Hypertension.

Background/Aims: A meta-analysis of randomized trials performed in healthy asymptomatic individuals suggested that overall mortality may increase after Helicobacter pylori eradication despite a significant decrease in the gastric cancer incidence and mortality rates. This retrospective population-based cohort study investigated if H. pylori treatment is associated with an increase in overall mortality in patients with hypertension. Methods: From the database of the Korean National Health Insurance Sample Cohort, we selected 198,487 patients treated for hypertension between 2002 and 2010. Those who received H. pylori treatment (H. pylori treatment cohort, 5,541 patients) were matched to those who did not (nontreatment cohort, 11,082 patients) at the ratio of 1 to 2. The primary outcome was the risk of overall mortality. The secondary outcomes were the risks of mortality due to cardiovascular disease, cerebrovascular disease, and cancer. The outcomes were evaluated from 6 months after H. pylori treatment to December 2013. A Cox proportional hazard model was used to estimate the hazard ratios (HRs). Results: During a median follow-up period of 4.8 years, death from any cause was reported in 4.1% of the patients in the H. pylori treatment cohort and 5.5% of the patients in the nontreatment cohort. The adjusted HR (aHR) for overall mortality in the H. pylori treatment cohort was 0.70 (95% confidence interval [CI], 0.60 to 0.82; p<0.001). With regard to cause-specific mortality, compared with the nontreatment cohort, the H. pylori treatment cohort had a lower risk of mortality due to cerebrovascular disease (aHR, 0.46; 95% CI, 0.26 to 0.81; p=0.007). The risks of mortality due to cancer and cardiovascular disease were not different between the cohorts. Conclusions: H. pylori treatment is not associated with an increase in overall mortality in patients treated for hypertension.

Considerations for patient selection: Prepectoral versus subpectoral implant-based breast reconstruction.

BACKGROUND: In recent years, breast implants have been frequently placed in the subcutaneous pocket, in the so-called prepectoral approach. We report our technique of prepectoral implant-based breast reconstruction (IBR), as well as its surgical and aesthetic outcomes, in comparison with subpectoral IBR. We also discuss relevant considerations and pitfalls in prepectoral IBR and suggest an algorithm for the selection of patients for IBR based on our experiences. METHODS: We performed 79 immediate breast reconstructions with a breast implant and an acellular dermal matrix (ADM) sling, of which 47 were subpectoral IBRs and 32 were prepectoral IBRs. Two-stage IBR was performed in 36 cases (20 subpectoral, 16 prepectoral), and direct-to-implant IBR in 43 cases (27 prepectoral, 16 subpectoral). The ADM sling supplemented the inferolateral side of the breast prosthesis in the subpectoral group and covered the entire anterior surface of the breast prosthesis in the prepectoral group. RESULTS: The postoperative pain score was much lower in the prepectoral group than in the subpectoral group (1.78 vs. 7.17). The incidence of seroma was higher in the prepectoral group (31.3% vs. 6.4%). Other postoperative complications, such as surgical site infection, flap necrosis, implant failure, and wound dehiscence, occurred at similar rates in both groups. Animation deformities developed in 8.5% of patients in the subpectoral group and rippling deformities were more common in the prepectoral group (21.9% vs. 12.8%). CONCLUSIONS: The indications for prepectoral IBR include moderately-sized breasts with a thick well-vascularized mastectomy flap and concomitant bilateral breast reconstruction with prophylactic mastectomy.

Customized reconstruction with modified keystone flaps.

The reconstruction of soft tissue defects with a similar type of tissue and minimizing morbidities are important. Herein, we describe our surgical experience using customized reconstruction with a series of modified keystone flaps. We retrospectively reviewed data of 48 consecutive soft tissue reconstructions using modified keystone flaps between March and December 2017. Soft tissue reconstruction was performed and there was no major complication in the follow-up period. The dimensions of the wound defect ranged from 1 × 1 cm2 to 20 × 18 cm2 with a mean size of 4.7 × 3.5 cm2 , while the dimensions of the customized keystone design flap ranged from 2 × 1 cm2 to 23 × 19 cm2 with a mean size of 7.9 × 5.4 cm2 . Minor dehiscence in three cases (6%) and partial flap loss in one case (2%) were noticed. Two cases healed spontaneously and other two cases were surgically recovered. Due to its simplicity, reliability, versatility and minimal morbidity, our modified keystone flaps could be excellent surgical options in various soft tissue reconstructions.

The fortune cookie flap for aesthetic reconstruction after chest keloid resection: a small case series.

BACKGROUND: Generally, the recurrence rate of keloids is unacceptably high after surgical excision alone. Nevertheless, surgical reduction of keloids is inevitable in many cases. The reconstruction of extensive soft tissue defects following complete keloid resection is challenging to surgeons. In this study, we present our clinical experience using a novel fortune cookie flap for treating chest keloids. This flap provides an excellent surgical option that maintains natural appearance with minimal donor-site morbidity. METHODS: We retrospectively reviewed the data from 3 consecutive cases of reconstruction using the fortune cookie flap following resection of chest keloids between March and December, 2017. RESULTS: Successful reconstructions were performed without any major complications. The mean dimensions of the reconstructed defect were 5.0 × 4.2 cm, while the mean dimensions of the flap were 7.7 × 5.7 cm. CONCLUSIONS: Owing to its simplicity, reliability, versatility, minimal morbidity and excellent aesthetics, the fortune cookie flap is as an excellent option for reconstruction following complete keloid resection on the chest.

Botulinum toxin A increases allograft tolerance in an experimental transplantation model: a preliminary study.

Identifying novel and safe immunosuppressants is of crucial importance. Recently, there have been several studies revealing that botulinum toxin A (BoTA) significantly alleviates ischemia-reperfusion injuries. Emerging evidence shows that ischemia-reperfusion injuries contribute to innate immune activation, promoting rejection, and inhibiting tolerance. Therefore, we hypothesized that a pretreatment with BoTA might decrease allograft rejection in a rat transplantation model. Twenty-four Lewis (LEW) rats were randomly assigned into two groups consisting of 12 rats each, depending on whether skin allograft was performed after pretreatment with BoTA (BoTA group) or with normal saline (control group). The experimental group was pretreated with a subcutaneous injection of BoTA (10 IU), while the control group was pretreated with normal saline 5 days prior to surgery. The donor Brown-Norway (BN) rat dorsal skin was subsequently grafted to the recipient LEW rats. The recipient wounds, measuring 2 cm × 2 cm, were made via dorsal skin excision through the panniculus carnosus. The donor skins of the same dimensions were obtained and transplanted on to the wounds and sutured with 4-0 nylon sutures. Mean graft survival time was measured in both groups. Quantitative reverse-transcriptase PCR and Western blotting were performed to evaluate the gene/protein expression of CD4 and VEGF. The mean graft survival time in the BoTA group was significantly longer than that of the control group (P=0.004). The relative mRNA and protein expression of CD4 was significantly lower in the BoTA group (P<0.001), while the relative mRNA and protein expression of VEGF was significantly higher in the BoTA group (P<0.001). In conclusion, our results show that BoTA prolongs the survival of skin allografts in a rat transplantation model.

Semilunar Flap for Minimizing the Scar Length in Nipple Reconstruction.

Nipple reconstruction is an essential procedure to change an amorphous breast mound to a distinct breast. Various skin flaps have been proposed for nipple reconstruction. In the C-V flap technique, which is one of the most commonly used flaps for nipple reconstruction, the scar that is developed after closure of the donor site of the V-flap frequently extends beyond a new areola area. To reduce the length of the donor site scar, various modifications of the C-V flap have been proposed. We adopted the semilunar flap instead of the V flap of C-V flap by changing the angle of V flap for nipple reconstruction. The semilunar flap design allowed generation of a donor flap with sufficient width and length of the skin flap for a nipple barrel without increasing the length of the donor site scar. In most cases, the semilunar flaps showed stable outcomes and resulted in angled donor-site scars that were usually located within the boundary of a new areola. We think the semilunar flap represents a good alternative method in nipple reconstruction by changing the angle of the donor-site scar and leaving the scar length within the new areolar area.

Postoperative Changes in Isolated Medial Orbital Wall Fractures Based on Computed Tomography.

The treatment has been improved on the accurate reduction of blow-out fracture for many decades. But still, it has been limited to reduce completely when surgeons are approaching by conventional technique. The authors analyzed the postoperative results using computed tomography (CT) scans after conventional open reduction of isolated medial wall fracture. Thirty-seven patients with isolated medial wall fracture were reviewed. All patients underwent preoperative, immediate, and postoperative CT scans. Two surgeons have performed the surgery by conventional open reduction with transcaruncular approach and absorbable mesh insertion. The authors evaluated changing orbital volume and distance, comparing the immediate and 6 months postoperative outcomes with preoperative outcome. The differences between immediate postoperative and 6 months postoperatively data were statistically evaluated. The authors used the distant value to minimize bias of CT view selection. Significant differences from the 2 kinds of data were observed (P < 0.05 for volume, P < 0.01 for distance, Paired t test). Bone remodeling process after conventional open reduction of orbital wall has not been fully understood. Most popular technique is conventional open reduction and mesh insertion but it is not easy for surgeons to reduce fractured bones completely. The authors analyzed the bone remodeling after incomplete reduction. These results suggest that the decreased measurements might be caused from the scar contracture with fibrosis. This research is very limited to explain the change while bone remodeling is progressed. Further research should be continued to discover the understanding of the process.

Thyroid Hormone Receptor Alpha is Essential to Maintain the Satellite Cell Niche During Skeletal Muscle Injury and Sarcopenia of Aging.

BACKGROUND: Myopathic changes are commonly described in hypothyroid and hyperthyroid patients, including muscular atrophy and weakness. Satellite cells (SCs) play a major role in skeletal muscle maintenance and regeneration after injury. A mouse model of resistance to thyroid hormone-TRα1PV demonstrated impaired skeletal muscle regeneration after injury with significant reduction of SCs, suggesting that exhaustion of the SC pool contributes to the impaired regeneration. To test this hypothesis, SC activation and proliferation were analyzed in vivo in response to skeletal muscle injury and during aging. METHODS: SCs of TRα1PV male mice were analyzed four days after cardiotoxin-induced muscle injury, and they were compared to wild-type (WT) male animals. TRα-knockdown C2C12 myoblasts were injected into injured skeletal muscle, and four days after transplantation, the in vivo behavior was compared to control C2C12 myoblasts. Skeletal muscle regeneration was compared in younger and older TRα1PV and WT animals. RESULTS: The total number of SCs in skeletal muscle of TRα1PV mice was significantly lower than control, both before and shortly after muscle injury, with significant impairment of SC activation, consistent with SC pool exhaustion. TRα-knockdown myoblasts showed impaired in vivo proliferation and migration. TRα1PV mice had skeletal muscle loss and significant impairment in skeletal muscle regeneration with aging. This translated to a significant reduction of the SC pool with aging compared to WT mice. CONCLUSION: TRα plays an important role in the maintenance of the SC pool. Impaired skeletal muscle regeneration in TRα1PV mice is associated with insufficient SC activation and proliferation, as well as the progressive loss of the SC pool with aging. Regulation of the SC pool and SC proliferation provides a therapeutic target to enhance skeletal muscle regeneration and possibly slow age-associated sarcopenia.

Advantages of intraoral and transconjunctival approaches for posterior displacement of a fractured zygomaticomaxillary complex.

BACKGROUND: Fracture of the zygomaticomaxillary complex (ZMC) is one of the most common facial injuries. A previous study has performed 3D analyses of the parallel and rotational displacements that occur in a fractured ZMC. However, few studies have investigated adequate fixation methods according to these displacements. Here, we assessed whether specific approaches and fixation methods for displacement of ZMC fractures produce esthetic results. METHODS: Hospital records and pre- and post-surgical computed tomographic scans of patients treated for ZMC fractures at the Department of Oral and Maxillofacial Surgery, College of Dentistry, Wonkwang University, between January 2010 and December 2015, were selected. Data were analyzed according to the direction of displacement and post-reduction prognosis using a 3D software. RESULTS: With ZMC fractures, displacement in the posterior direction occurred most frequently, while displacement in the superior-inferior direction was rare. A reduction using a transconjunctival approach and an intraoral approach was statistically better than that using an intraoral approach, Gillies approach, and lateral canthotomy approach for a posterior displacement (P < 0.05). CONCLUSIONS: When posterior displacement of a fractured ZMC occurs, use of an intraoral approach and transconjunctival approach simultaneously is recommended for reducing and fixing the displaced fragment accurately.

Changes of lip morphology following mandibular setback surgery using 3D cone-beam computed tomography images.

BACKGROUND: The aims of this study are to evaluate the lip morphology and change of lip commissure after mandibular setback surgery (MSS) for class III patients and analyze association between the amount of mandibular setback and change of lip morphology. METHODS: The samples consisted of 14 class III patients treated with MSS using bilateral sagittal split ramus osteotomy. Lateral cephalogram and cone-beam CT were taken before and about 6 months after MSS. Changes in landmarks and variables were measured with 3D software program Ondemand™. Paired and independent t tests were performed for statistical analysis. RESULTS: Landmarks in the mouth corner (cheilion, Ch) moved backward and downward (p < .005, p < .01). However, cheilion width was not statistically significantly changed. Landmark in labrale superius (Ls) was not altered significantly. Upper lip prominence angle (ChRt-Ls-ChLt °) became acute. Landmarks in stomion (Stm), labrale inferius (Li) moved backward (p < .005, p < .001). Lower lip prominence angle (ChRt-Li-ChLt °) became obtuse (p < .001). Height of the upper and lower lips was not altered significantly. Length of the upper lip vermilion was increased (p =< 0.01), and length of the lower lip vermilion was decreased (p < .05). Lip area on frontal view was not statistically significantly changed, but the upper lip area on lateral view was increased and change of the lower lip area decreased (p > .05, p < .005). On lateral view, upper lip prominent point (UP) moved downward and stomion moved backward and upward and the angle of Ls-UP-Stm (°) was decreased. Lower lip prominent point (LP) moved backward and downward, and the angle of Stm-LP-Li (°) was increased. Li moved backward. Finally, landmarks in the lower incisor tip (L1) moved backward and upward, but stomion moved downward. After surgery, lower incisor tip (L1) was positioned more superiorly than stomion (p < .05). There were significant associations between horizontal soft tissue and corresponding hard tissue. The posterior movement of L1 was related to statistically significantly about backward and downward movement of cheilion. CONCLUSIONS: The lip morphology of patients with dento-skeletal class III malocclusion shows a significant improvement after orthognathic surgery. Three-dimensional lip morphology changes in class III patients after MSS exhibited that cheilion moved backward and downward, upper lip projection angle became acute, lower lip projection angle became obtuse, change of upper lip area on lateral view was increased, change of lower lip area decreased, and morphology of lower lip was protruding. L1 was concerned with the lip tissue change in statistically significant way.

Thyroid Hormone Receptor α Plays an Essential Role in Male Skeletal Muscle Myoblast Proliferation, Differentiation, and Response to Injury.

Thyroid hormone plays an essential role in myogenesis, the process required for skeletal muscle development and repair, although the mechanisms have not been established. Skeletal muscle develops from the fusion of precursor myoblasts into myofibers. We have used the C2C12 skeletal muscle myoblast cell line, primary myoblasts, and mouse models of resistance to thyroid hormone (RTH) α and ß, to determine the role of thyroid hormone in the regulation of myoblast differentiation. T3, which activates thyroid hormone receptor (TR) α and ß, increased myoblast differentiation whereas GC1, a selective TRß agonist, was minimally effective. Genetic approaches confirmed that TRα plays an important role in normal myoblast proliferation and differentiation and acts through the Wnt/ß-catenin signaling pathway. Myoblasts with TRα knockdown, or derived from RTH-TRα PV (a frame-shift mutation) mice, displayed reduced proliferation and myogenic differentiation. Moreover, skeletal muscle from the TRα1PV mutant mouse had impaired in vivo regeneration after injury. RTH-TRß PV mutant mouse model skeletal muscle and derived primary myoblasts did not have altered proliferation, myogenic differentiation, or response to injury when compared with control. In conclusion, TRα plays an essential role in myoblast homeostasis and provides a potential therapeutic target to enhance skeletal muscle regeneration.

ß-Cell regeneration mediated by human bone marrow mesenchymal stem cells.

Bone marrow mesenchymal stem cells (BMSCs) have been shown to ameliorate diabetes in animal models. The mechanism, however, remains largely unknown. An unanswered question is whether BMSCs are able to differentiate into ß-cells in vivo, or whether BMSCs are able to mediate recovery and/or regeneration of endogenous ß-cells. Here we examined these questions by testing the ability of hBMSCs genetically modified to transiently express vascular endothelial growth factor (VEGF) or pancreatic-duodenal homeobox 1 (PDX1) to reverse diabetes and whether these cells were differentiated into ß-cells or mediated recovery through alternative mechanisms. Human BMSCs expressing VEGF and PDX1 reversed hyperglycemia in more than half of the diabetic mice and induced overall improved survival and weight maintenance in all mice. Recovery was sustained only in the mice treated with hBMSCs-VEGF. However, de novo ß-cell differentiation from human cells was observed in mice in both cases, treated with either hBMSCs-VEGF or hBMSCs- PDX1, confirmed by detectable level of serum human insulin. Sustained reversion of diabetes mediated by hBMSCs-VEGF was secondary to endogenous ß-cell regeneration and correlated with activation of the insulin/IGF receptor signaling pathway involved in maintaining ß-cell mass and function. Our study demonstrated the possible benefit of hBMSCs for the treatment of insulin-dependent diabetes and gives new insight into the mechanism of ß-cell recovery after injury mediated by hBMSC therapy.

Gemcitabine-releasing polymeric films for covered self-expandable metallic stent in treatment of gastrointestinal cancer.

Non-vascular drug-eluting stents have been studied for the treatment of gastrointestinal cancer and cancer-related stenosis. In this study, we designed and evaluated a gemcitabine (GEM)-eluting covered nonvascular stent. Polyurethane (PU)/polytetrafluoroethylene (PTFE) film was selected for the drug loading and eluting membrane. The membrane was fabricated by dip-coating on a Teflon bar (∅; 10mm), air-dried, peeled off and applied to a self-expanding Nitinol stent. Various amounts of poloxamer 407 (PL, Lutrol F127, BASF) (8%, 10%, or 12% of PU by weight) were added to control the release of GEM from membranes. The membrane containing 12% PL (GEM-PU-PL12%) showed the most favourable release properties; 70% of the loaded GEM released within 35 days, including the 35% released during the initial burst. The biological activities of GEM-PU-PL12% were evaluated using human cholangiocarcinoma cells (SK-ChA-1). GEM-PU-PL12% most efficiently inhibited the proliferation of cholangiocarcinoma cells and most highly induced pro-inflammatory cytokines (TNF-α, IL-1ß and IL-12) and p38 MAPKs in the cells. Subtumoural insertion of the GEM-PU-PL12% membrane more efficiently inhibited the growth of CT-26 colon cancer than other membranes. In this study, the GEM-eluting metal stents covered with PU-PL12% showed considerable feasibility for the treatment of malignant gastrointestinal cancer as well as cancer-related stenosis.

Immunotherapy targeting glioma stem cells--insights and perspectives.

INTRODUCTION: Glioblastoma multiforme (GBM) is the most aggressive and lethal primary malignant brain tumor. Although progress has been made in current conventional therapies for GBM patients, the effect of these advances on clinical outcomes has been disappointing. Recent research into the origin of cancers suggest that GBM cancer stem cells (GSC) are the source of initial tumor formation, resistance to current conventional therapeutics and eventual patient relapse. Currently, there are very few studies that apply immunotherapy to target GSC. AREAS COVERED: CD133, a cell surface protein, is used extensively as a surface marker to identify and isolate GSC in malignant glioma. We discuss biomarkers such as CD133, L1-cell adhesion molecule (L1-CAM), and A20 of GSC. We review developing novel treatment modalities, including immunotherapy strategies, to target GSC. EXPERT OPINION: There are very few reports of preclinical studies targeting GSC. Identification and validation of unique molecular signatures and elucidation of signaling pathways involved in survival, proliferation and differentiation of GSC will significantly advance this field and provide a framework for the rational design of a new generation of antigen-specific, anti-GSC immunotherapy- and nanotechnology-based targeted therapyies. Combined with other therapeutic avenues, GSC-targeting therapies may represent a new paradigm to treat GBM patients.