Revascularization vs. Medical Therapy for Coronary Chronic Total Occlusions in Patients With Chronic Kidney Disease.

BACKGROUND: We investigated whether the outcome of revascularization differed from the outcome of medical therapy in chronic kidney disease (CKD) and non-CKD patients with chronic total occlusion (CTO).Methods and Results:A total of 2,010 patients with CTO who underwent revascularization (n=1,355), including percutaneous coronary intervention (n=878) and coronary artery bypass grafting (n=477), or had medical therapy alone (n=655) were examined. The primary outcome was all-cause death during follow-up. Among the non-CKD patients (n=1,679), revascularization had a lower incidence of all-cause death (adjusted hazard ratio [HR] 0.54, 95% confidence interval [CI] 0.41-0.72, P<0.001) compared with medical therapy. Among the CKD patients (n=331), the difference in the incidence of all-cause death was not as marked between the 2 treatments (adjusted HR 0.71, 95% CI 0.48-1.06, P=0.09). There was a significant interaction between kidney function and treatment strategy (revascularization vs. medical therapy) on all-cause death (P for interaction=0.014). CONCLUSIONS: Based on the clinical outcomes, in CTO patients with preexisting CKD, revascularization via PCI or bypass surgery might not be as effective as in non-CKD patients.

Impact of different nitrate therapies on long-term clinical outcomes of patients with vasospastic angina: A propensity score-matched analysis.

BACKGROUND: Despite the short-term vasodilatory effects of nitrates, the prognostic effects of long-term nitrate therapy in patients with vasospastic angina (VSA) remains unclear. We investigated the prognostic impact of chronic nitrate therapy in VSA patients. METHODS: Between January 2003 and December 2014, a total of 1154 VSA patients proven by ergonovine provocation tests were classified into nitrate (n=676) and non-nitrate (n=478) groups according to prescriptions for oral nitrates, including isosorbide mononitrate (ISMN) and nicorandil. The primary outcome was major adverse cardiovascular events (MACE), defined as a composite of cardiac death, myocardial infarction, any revascularization, or rehospitalization due to recurrent angina. RESULTS: The nitrate group was found to have a higher risk of MACE (22.9% vs. 17.6%, hazard ratio [HR] 1.32, 95% confidence interval [CI] 1.01-1.73, p=0.043) than the non-nitrate group. After propensity score matching, the nitrate group had greater risks of MACE (HR 1.32, 95%CI 1.01-1.73, p=0.049). Patients who received the immediate-release formula of ISMN (HR 1.80, 95%CI 1.35-2.39, p<0.001) or were administered any forms of ISMN other than at bedtime (HR 1.90, 95%CI 1.41-2.57, p<0.001) had a significantly higher risk of MACE compared with the non-nitrate group. Nicorandil was shown to have a neutral effect on VSA patients (HR 1.11, 95%CI 0.73-1.69, p=0.62). CONCLUSIONS: The long-term use of nitrate therapy was associated with increased risk of adverse cardiac events in VSA patients. The use of immediate-release ISMN or the administration of ISMN other than at bedtime was related with poor outcomes of VSA patients.

Safety and tolerability of intradiscal implantation of combined autologous adipose-derived mesenchymal stem cells and hyaluronic acid in patients with chronic discogenic low back pain: 1-year follow-up of a phase I study.

BACKGROUND: Adipose tissue-derived mesenchymal stem cells (AT-MSCs) offer potential as a therapeutic option for chronic discogenic low back pain (LBP) because of their immunomodulatory functions and capacity for cartilage differentiation. The goal of this study was to assess the safety and tolerability of a single intradiscal implantation of combined AT-MSCs and hyaluronic acid (HA) derivative in patients with chronic discogenic LBP. METHODS: We performed a single-arm phase I clinical trial with a 12-month follow-up and enrolled 10 eligible chronic LBP patients. Chronic LBP had lasted for more than 3 months with a minimum intensity of 4/10 on a visual analogue scale (VAS) and disability level ≥ 30% on the Oswestry Disability Index (ODI). The 10 patients underwent a single intradiscal injection of combined HA derivative and AT-MSCs at a dose of 2 × 107 cells/disc (n = 5) or 4 × 107 cells/disc (n = 5). Safety and treatment outcomes were evaluated by assessing VAS, ODI, Short Form-36 (SF-36), and imaging (lumbar spine X-ray imaging and MRI) at regular intervals over 1 year. RESULTS: No patients were lost at any point during the 1-year clinical study. We observed no procedure or stem cell-related adverse events or serious adverse events during the 1-year follow-up period. VAS, ODI, and SF-36 scores significantly improved in both groups receiving both low (cases 2, 4, and 5) and high (cases 7, 8, and 9) cell doses, and did not differ significantly between the two groups. Among six patients who achieved significant improvement in VAS, ODI, and SF-36, three patients (cases 4, 8, and 9) were determined to have increased water content based on an increased apparent diffusion coefficient on diffusion MRI. CONCLUSIONS: Combined implantation of AT-MSCs and HA derivative in chronic discogenic LBP is safe and tolerable. However, the efficacy of combined AT-MSCs and HA should be investigated in a randomized controlled trial in a larger population. TRIAL REGISTRATION: ClinicalTrials.gov NCT02338271 . Registered 7 January 2015.

Trichilemmal Carcinoma from Proliferating Trichilemmal Cyst on the Posterior Neck.

Trichilemmal cysts are common fluid-filled growths that arise from the isthmus of the hair follicle. They can form rapidly multiplying trichilemmal tumors-, also called proliferating trichilemmal cysts, which are typically benign. Rarely, proliferating trichilemmal cysts can become cancerous. Here we report the case of a patient who experienced this series of changes. The 27-year-old male patient had been observed to have a 1×1 cm cyst 7 years ago. Eight months prior to presentation at our institution, incision and drainage was performed at his local clinic. However, the size of the mass had gradually increased. At our clinic, he presented with a 5×4 cm hard mass that had recurred on the posterior side of his neck. The tumor was removed without safety margin, and the skin defect was covered with a split-thickness skin graft. The pathologic diagnosis was a benign proliferating trichilemmal cyst. The mass recurred after 4months, at which point, a wide excision (1.3-cm safety margin) and split-thickness skin graft were performed. The biopsy revealed a trichilemmal carcinoma arising from a proliferating trichilemmal cyst. This clinical experience suggests that clinicians should consider the possibility of malignant changes when diagnosing and treating trichilemmal cysts.

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.

Netrin-1-Induced Stem Cell Bioactivity Contributes to the Regeneration of Injured Tissues via the Lipid Raft-Dependent Integrin α6ß4 Signaling Pathway.

Netrin-1 (Ntn-1) is a multifunctional neuronal signaling molecule; however, its physiological significance, which improves the tissue-regeneration capacity of stem cells, has not been characterized. In the present study, we investigate the mechanism by which Ntn-1 promotes the proliferation of hUCB-MSCs with regard to the regeneration of injured tissues. We found that Ntn-1 induces the proliferation of hUCB-MSCs mainly via Inα6ß4 coupled with c-Src. Ntn-1 induced the recruitment of NADPH oxidases and Rac1 into membrane lipid rafts to facilitate ROS production. The Inα6ß4 signaling of Ntn-1 through ROS production is uniquely mediated by the activation of SP1 for cell cycle progression and the transcriptional occupancy of SP1 on the VEGF promoter. Moreover, Ntn-1 has the ability to induce the F-actin reorganization of hUCB-MSCs via the Inα6ß4 signaling pathway. In an in vivo model, transplantation of hUCB-MSCs pre-treated with Ntn-1 enhanced the skin wound healing process, where relatively more angiogenesis was detected. The potential effect of Ntn-1 on angiogenesis is further verified by the mouse hindlimb ischemia model, where the pre-activation of hUCB-MSCs with Ntn-1 significantly improved vascular regeneration. These results demonstrate that Ntn-1 plays an important role in the tissue regeneration process of hUCB-MSC via the lipid raft-mediated Inα6ß4 signaling pathway.

Prospective 1-Year Follow-Up Study of Breast Augmentation by Cell-Assisted Lipotransfer.

BACKGROUND: Breast augmentation by cell-assisted lipotransfer (CAL) may achieve a more natural breast contour than silicone implants. Moreover, certain complications associated with these prosthetic devices can be avoided with CAL. Few prospective studies of CAL have been performed to examine long-term volume changes, effects on breast parenchymal tissue, and the effect of stromal vascular fraction (SVF) on graft survival. OBJECTIVES: In a 1-year prospective study of patients who underwent CAL, the authors examined changes in breast volume, effects on parenchymal tissue, and the impact of SVF on graft survival. METHODS: Following preoperative radiologic examination, patients underwent primary augmentation mammaplasty by CAL to both breasts. The SVF was characterized, and changes in breast volume were determined from magnetic resonance imaging studies performed postoperatively at 3 months and 1 year. A breast-imaging specialist reviewed all scans to detect changes in breasts. RESULTS: Five patients (10 breasts) were enrolled. Averagely 23% of grafted fat in volume was additionally harvested from each patient to isolate SVF cells. One year after CAL, breast volume had decreased to 47% of the initial postoperative volume. There was no parenchymal changes except small oil cysts. The ratio of SVF cell count to grafted fat volume showed no correlation with graft survival. Patterns of breast-volume decrease differed between older women with a history of breastfeeding and younger women without a history of breastfeeding. CONCLUSIONS: The addition of SVF cells did not appear to improve the retention of grafted fat in these patients. Skin tension may be an important factor influencing the absorption pattern of grafted fat. LEVEL OF EVIDENCE 4: Therapeutic.

Human Embryonic Stem Cell-Derived Endothelial Precursor Cell Conditioned Medium Reduces the Thickness of the Capsule Around Silicone Implants in Rats.

BACKGROUND: We postulated that the fibrotic capsule around a silicone implant could be induced by ischemic conditions, based on previous reports that hypoxia is an important microenvironmental factor in the development of tissue fibrosis. OBJECTIVE: This study aimed to determine the effect of human embryonic stem cell (hESC)-derived endothelial precursor cell (EPC) conditioned medium (CM), which has strong angiogenic potential, on the development of capsule around the silicone implant in a rat model. METHODS AND MATERIALS: Three groups had a mini-silicone implant with a smooth surface inserted. In 2 experimental groups, hESC-EPC CM was administered into the subcutaneous pocket either 1 or 2 times. After 2 months, the capsules were harvested and analyzed by histologic examination. RESULTS: There was a significant reduction in the thickness of the peri-implant capsules (P < 0.05) between the control and experimental groups. There is no tendency that hESC-EPC CM reduces inflammatory reaction in early postoperative periods. The experimental group showed increased angiogenesis compared to the control group (P < 0.05). CONCLUSIONS: Tissue hypoxia around the implant may be another cause for the peri-implant capsule. A preventive or therapeutic strategy to decrease capsular contracture by relieving the ischemic condition around the implant can be investigated in the future.

Antifibrogenic effects of B16 melanoma-conditioned medium.

BACKGROUND: Some malignant cancers show high levels of local invasiveness by the secretion of soluble factors that can degrade adjacent tissues and suppress surrounding cell growth. We investigated the possibility of treating fibroproliferative scars based on these properties of malignant melanoma. MATERIAL AND METHODS: B16 melanoma-conditioned medium (B16 M-CM) was added to keloid fibroblasts (KFs), and proliferation, migration, and type I collagen production were measured. The cell cycle and signaling pathways were also analyzed. Proteins associated with cell proliferation were measured with Western blot analysis. Animal experiments using a rabbit ear model was performed to confirm the effect of B16 M-CM in vivo. RESULTS: B16 M-CM reduced proliferation, migration, and type I collagen production of KFs. This treatment also increased the number of cells in the subG1 phase and decreased phosphorylation levels of AKT, extracellular signal-regulated kinase1/2, cyclin D1, and c-Myc of KFs. Additionally, B16 M-CM reduced the thickness of rabbit ear scars in the rabbit ear model in vivo. CONCLUSIONS: B16 M-CM can suppress proliferation, migration, and type I collagen production of KFs. In addition, concentrated B16 M-CM reduced scar thickness in the rabbit ear model. The specific proteins involved should be identified in a future study.

Transport distraction osteogenesis with recombinant human bone morphogenic protein-2 for large calvarial defect reconstruction.

BACKGROUND: Transport distraction osteogenesis (TDO) has been used in attempts to treat large calvarial defects but has, until now, lacked consistency and reliability. To achieve sufficient bone formation, the effect of TDO was compared to the effect of TDO combined with recombinant human bone morphogenic protein-2 (rhBMP-2). METHODS: Fourteen dogs were divided into 2 groups; 6 animals in the control group received TDO only, and 8 received TDO combined with rhBMP-2. A calvarial defect 33 × 35 mm in size was generated, and the drug-delivering internal distractor was applied. After a 5-day latency period, distraction with rhBMP-2 at 10 µg/day was initiated at a rate of 2 mm/day. This was followed by a consolidation period of 3 months, after which areas of osteogenesis and strength were measured and histologic examinations were conducted. RESULTS: The average area of osteogenesis was higher in the experimental group (P < 0.01). Regenerated bone of the experimental group showed increased strength (P < 0.05). Histological examination showed typical mature bone in the experimental group. Prominent osteoblastic rimming was observed in the bone marrow of the experimental group. CONCLUSIONS: TDO with an internal distraction device delivering rhBMP-2 can enhance bone regeneration of large calvarial defects in a dog model. These results suggest the potential for human clinical testing of TDO combined with rhBMP-2.

Cheek drooping in 2 patients with maxillary fractures after rigid fixation with bioabsorbable mesh.

Bioabsorbable plate-screw systems are commonly used for the internal fixation of facial bone fractures. The anterior maxilla has a unique curved shape, and fractured bony fragments tend to be small and fragile; therefore, more effective rigid fixation can be achieved using a molded bioabsorbable mesh rather than a bioabsorbable plate. Herein, we describe 2 patients with cheek drooping after a rigid fixation of comminuted maxillary fracture using bioabsorbable meshes and screws.The postoperative courses were uneventful, but both showed soft tissue bulging in the cheek area of the operation site for 12 to 13 months after the operation. No other symptom or sign related to inflammation or foreign body reaction was noted.In comminuted maxillary fractures, bone fragments are more conveniently fixed with a 1-piece molded bioabsorbable mesh. However, it is believed that a single large mesh may interfere with adhesion between the maxillary surface and the overlying soft tissue. Therefore, we recommend using the least amount of mesh to fixate maxillary bone fragments.

Fingertip reconstruction with simultaneous flaps and nail bed grafts following amputation.

PURPOSE: To report our technique and results with treating fingertip amputations with flaps and simultaneous nailbed grafts. METHODS: We reconstructed 20 fingertip amputations with loss of bone and nail with flaps combined with nailbed grafts. We reconstructed the volar side of the fingertip with a flap, and the dorsal side of the fingertip with a nailbed grafted to the raw inner surface of the flap. We employed volar V-Y advancement flaps for transverse or dorsal oblique fingertip injuries and generally used abdominal flaps for volar oblique fingertip injuries. We harvested nailbeds from the amputated finger or from the patient's first toe. RESULTS: The length of the amputated fingertips was restored with the flaps, and the lost nailbeds were restored to their natural appearance with the nailbed grafts. We classified the results according to the length of the reconstructed fingertip and the appearance of the nail. Excellent or good results were achieved in 16 cases. Three cases had fair results and 1 had a poor result. We observed favorable results for distal fingertip amputations (Allen type II or III). In particular, most cases that were reconstructed with volar V-Y advancement flaps combined with nailbed grafts demonstrated favorable results. CONCLUSIONS: This method is useful for the restoration of dorsal oblique or transverse type fingertip amputations and is a good alternative when replantation is not an option.

Eyelid dynamics and supratarsal crease appearance after double eyelid surgery.

BACKGROUND: Although double eyelid surgery is one of the most common cosmetic surgeries among Asians, there are few reports to confirm the physiology of eye blinking after such surgeries. This study analyzed eyelid dynamics and supratarsal crease appearance after double eyelid surgery using a high-speed digital camera to provide precise movement detection. METHODS: Twenty healthy volunteers and 15 patients who underwent double eyelid surgery with tarsodermal fixation were studied. Using the slow-motion replay setting of a high-speed digital camera, the patients' spontaneous eye blinking was analyzed for (1) blink duration, (2) peak eyelid velocity, (3) blink rate, and (4) supratarsal crease appearance. RESULTS: After double eyelid surgery, there were no significant differences in blink duration, peak eyelid velocity, or blink rate compared with the control group. Regarding supratarsal crease appearance, dynamic creases were created in 6 of 15 patients, whereas 9 patients showed static creases. CONCLUSIONS: Double eyelid surgery with tarsodermal fixation does not alter lid dynamics of spontaneous eye blinking. Furthermore, the tarsodermal fixation method, which is known to create a static crease, could also lead to the development of a dynamic crease.

Treatment of frontal sinus fracture using bioabsorbable mesh plates.

Accurate reduction and stable fixation are important in the treatment of frontal sinus fracture. Usually, metal plates and screws were used because of easy handling and delicate fixation. However, palpability and possibility for secondary operation for plate removal were shortcomings. For improving these problems, we used absorbable mesh plate for fixation of reduced frontal bones.In this study, 14 patients with frontal sinus fracture were treated by open reduction and rigid fixation using absorbable mesh plates. Mean follow-up period was 17.6 months. Considering anterior and posterior table involvement, nasofrontal duct injury, and concomitant neurosurgical problems, additional surgical procedures including degloving sinus mucosa, cranialization, and obliteration of nasofrontal duct were also conducted.There was no remarkable early and late postoperative complication. Aesthetic results were also satisfactory. Absorbable mesh plates were easy to mold and convenient for screw fixation. Moreover, there was no necessity of secondary operation for removal of plates.We believe that absorbable mesh plates might be a useful material for fixation instead of metal plates and screws especially in mild to moderate degree of frontal bone fractures.