Effects of corticosteroids on expression of interleukin-18 in the airway mucosa of a mouse model of allergic rhinitis

OBJECTIVES: In this study, we aimed to investigate the release and response of interleukin (IL)-18 to steroid treatment in a mouse model of allergic rhinitis. METHODS: BALB/c mice were sensitized systemically by intraperitoneal injection of ovalbumin and locally by ovalbumin inhalation. Dexamethasone sodium phosphate was given by intraperitoneal injection in the steroid treatment group. Symptom scores, eosinophil counts, and IL-18 concentrations in the nasal and lung lavage fluids were analyzed. RESULTS: The symptom scores and eosinophil counts of the negative control and steroid treatment groups were significantly lower than those of the positive control group (p < .01). The mean IL-18 concentrations in the nasal lavage fluid were not significantly different among the three groups (56.68 +/- 9.57,63.39 +/- 8.93, and 64.47 +/- 6.83 pg/mL, respectively). The IL-18 concentrations in the lung lavage fluid were significantly different between the positive control group and the steroid treatment group (430.75 +/- 154.54 and 69.94 +/- 14.26 pg/mL, respectively, p = .028). CONCLUSIONS: The IL-18 concentration was found to be increased in the lung lavage fluid, but not in the nasal lavage fluid, in a mouse model of allergic rhinitis. Increased IL-18 concentrations returned toward the previous concentrations after steroid treatment. These results suggest that the roles of IL-18 may be different in the pathogenesis of allergic rhinitis and the pathogenesis of asthma.     

Neovascular potential of adipose‐derived stromal cells (ASCs) from diabetic patients

We explored the vascular biology of adipose‐derived stromal cells (ASCs) from diabetic patients and applied these cells to a murine ischemic flap model to assess the comparative angiogenic potentials between normal and diabetic human ASCs. ASCs were obtained from diabetic patients (n = 5) and controls (n = 5). Secretion and expression of angiogenic cytokines were measured under normoxic and hypoxic condition in vitro. Conditioned media harvested from ASC cultures were assessed for their ability to stimulate human umbilical vein endothelial cell proliferation and tubulization. The control and diabetic ASCs were injected into the murine ischemic flaps, and the surviving area was measured. Diabetic adipose‐derived stromal cells showed a lower level of vascular endothelial growth factor expression and cell proliferation rates than the control cells (p < 0.05). However, vascular endothelial growth factor, hepatocyte growth factor secretion, tubulogenesis, and cell proliferation in diabetic conditioned media were increased in response to hypoxic stimuli (p < 0.05), and it was similar to those of control cells. In an animal study, diabetic and normal ASCs significantly increased flap survival (p < 0.05); however, the functional difference was not found between the two groups. Diabetic ASCs were impaired in their ability to produce vascular endothelial growth factors and to induce cellular proliferation under hypoxic conditions. However, diabetic ASCs showed similar flap salvaging effect compared with controls. These findings may be important in the context of future study of autologous cell‐based therapy in diabetic patients.     

Sinonasal Glomangiopericytoma Causing Oncogenic Osteomalacia

A 60-year-old woman suffered from recurrent femur neck fracture. Laboratory data showed serum hypophosphatemia, elevated alkaline phosphatase, normal serum calcium levels, and normal parathyroid hormone levels. Radiological examinations revealed a tumor in the right maxillary alveolar bone. The nasal cavity mass was removed, and the histological features were those of glomangiopericytoma. After removal of the tumor, some of the laboratory data normalized. Based on the clinical features, histopathological diagnosis and postoperative course of events, a diagnosis of glomangiopericytoma causing oncogenic osteomalacia was confirmed. We report a case of oncogenic osteomalacia caused by sinonasal glomangiopericytoma.     

Genomic landscape of liposarcoma

Liposarcoma (LPS) is the most common type of soft tissue sarcoma accounting for 20% of all adult sarcomas. Due to absence of clinically effective treatment options in inoperable situations and resistance to chemotherapeutics, a critical need exists to identify novel therapeutic targets. We analyzed LPS genomic landscape using SNP arrays, whole exome sequencing and targeted exome sequencing to uncover the genomic information for development of specific anti-cancer targets. SNP array analysis indicated known amplified genes (MDM2, CDK4, HMGA2) and important novel genes (UAP1, MIR557, LAMA4, CPM, IGF2, ERBB3, IGF1R). Carboxypeptidase M (CPM), recurrently amplified gene in well-differentiated/de-differentiated LPS was noted as a putative oncogene involved in the EGFR pathway. Notable deletions were found at chromosome 1p (RUNX3, ARID1A), chromosome 11q (ATM, CHEK1) and chromosome 13q14.2 (MIR15A, MIR16-1). Significantly and recurrently mutated genes (false discovery rate < 0.05) included PLEC (27%), MXRA5 (21%), FAT3 (24%), NF1 (20%), MDC1 (10%), TP53 (7%) and CHEK2 (6%). Further, in vitro and in vivo functional studies provided evidence for the tumor suppressor role for Neurofibromin 1 (NF1) gene in different subtypes of LPS. Pathway analysis of recurrent mutations demonstrated signaling through MAPK, JAK-STAT, Wnt, ErbB, axon guidance, apoptosis, DNA damage repair and cell cycle pathways were involved in liposarcomagenesis. Interestingly, we also found mutational and copy number heterogeneity within a primary LPS tumor signifying the importance of multi-region sequencing for cancer-genome guided therapy. In summary, these findings provide insight into the genomic complexity of LPS and highlight potential druggable pathways for targeted therapeutic approach.     

Long-Term Clinical Course of Benign Fibro-Osseous Lesions in the Paranasal Sinuses

ObjectivesFibro-osseous lesions of the paranasal sinuses can present various clinical manifestations. This study aimed to report the long-term clinical course of benign fibro-osseous lesions (BFOLs) in the paranasal sinuses, including clinical and radiologic features.MethodsRadiologically confirmed BFOLs between 1994 and 2016, with the exclusion of osteoma cases, were retrospectively reviewed. We compared demographic characteristics between the surgery and observation groups. The reasons for the imaging study, radiographic features, histopathology, and clinical course based on serial image scans were analyzed.ResultsIn total, 183 subjects were selected from a thorough review of head and neck radiologic tests (n=606,068) at a tertiary referral hospital over 22 years. Patients’ mean age was 28.6±18.1 years, and 56.3% were males. A diagnostic imaging workup was performed in 55.7% of patients due to facial asymmetry, headache, skull mass, or other symptoms related to BFOLs. In other patients (37.7%), BFOLs were found incidentally on computed tomography or magnetic resonance imaging. The most common diagnosis was fibrous dysplasia, followed by ossifying fibroma, based on both radiologic exams and histopathologic results. In total, 42.6% of the patients underwent surgery because of subjective symptoms or esthetic concerns. The patients who underwent surgery were younger (P<0.001) and had a longer follow-up duration (P<0.001) than those who underwent observation. Patients who experienced lesion growth (11.5%) were younger (P<0.001) and had more lesion sites (P=0.018) than those who did not, regardless of surgical treatment. Five patients underwent optic nerve decompression, and one patient experienced malignant transformation.ConclusionBFOL in the paranasal sinuses is a rare disease, and most cases were observed without specific treatment. Surgical treatment should be considered in symptomatic patients with aggressive clinical features. Regular observation and management are needed, particularly in younger patients in their teens.     

Prevalence of lower airway diseases in patients with chronic rhinosinusitis

CONCLUSION: There is high prevalence of lower airway diseases in patients with chronic rhinosinusitis and frequently co-existing lower airway diseases have not been diagnosed before. OBJECTIVES: To examine the prevalence of lower airway diseases in patients with chronic rhinosinusitis. METHODS: Seventy-three consecutive patients with chronic rhinosinusitis were enrolled in this prospective study. With routine physical examination, spirometry and methacholine bronchial provocation test were performed and chest simple radiograph or chest computed tomography was taken. RESULTS: Thirty patients (41.1%) had lower airway diseases. There were 8 patients with asthma, 5 with asymptomatic bronchial hyperresponsiveness, 11 with small airway disease, 2 with chronic obstructive pulmonary disease and 4 with bronchiectasis. Of these 30 patients, 21 patients (70.0%) were first diagnosed as having lower airway diseases in this study.     

An anatomic study and clinical application of medial pedis flap in Asians

Several investigators have reported their clinical experience with medial pedis flaps for reconstruction of soft tissue defects of the hand and digits. In a cadaveric study in 1997, Jayme and Hamilton described the anatomy of the medial branch of the deep division of the medial plantar artery, which is used in the medial pedis flap. However, they had only a few cases where this flap was used. There have been no such anatomic studies in Korea to date. We found the medial pedis flap to be a reliable option for reconstruction of soft tissue defects of the hand and digits, based on an anatomic study with 10 dissected fresh cadavers (20 cases) and analyzing the clinical outcomes in 17 patients. An anatomic study revealed that there were some racial differences in the diameter and length of the vessels. The diameter of vessels in the Korean population is larger than that in whites. Using a thin, flexible medial pedis flap, which has skin and subcutaneous tissue similar to that of the volar aspect of the hand and digits, we harvested and performed the reconstruction on 17 patients with soft tissue defects of the hands and digits. The vessels used for this flap were the medial branch of the deep division of the medial plantar artery and vena comitantes, or subcutaneous veins. The mean size of the flap was 2.82 cm x 4.15 cm. All flaps were successful without any significant complications. The medial pedis flap possesses several advantages: (1) it is very thin in comparison to other standard free flaps; (2) it has 2 draining venous pathways; (3) it provides a good color and texture match for the hand and fingers; (4) it has a satisfactory recovery of protective sensation.