Years before insulin was discovered, anti-inflammatory sodium salicylate was used to treat diabetes in 1901. Intriguingly for many years that followed, diabetes was viewed as a disorder of glucose metabolism, and then it was described as a disease of dysregulated lipid metabolism. The diabetes research focused on the causal relationship between obesity and insulin resistance, a major characteristic of type 2 diabetes. It is only within the past 20 years when the notion of inflammation as a cause of insulin resistance began to surface. In obesity, inflammation develops when macrophages infiltrate adipose tissue and stimulate adipocyte secretion of inflammatory cytokines, that in turn affect energy balance, glucose and lipid metabolism, leading to insulin resistance. This report reviews recent discoveries of stress kinase signaling involving molecular scaffolds and endoplasmic reticulum chaperones that regulate energy balance and glucose homeostasis. As we advance from a conceptual understanding to molecular discoveries, a century-old story of inflammation and insulin resistance is re-born with new ideas.
Adipocytes ; Adipose Tissue ; Cytokines ; Endoplasmic Reticulum ; Glucose ; Homeostasis ; Inflammation ; Insulin ; Insulin Resistance ; Lipid Metabolism ; Macrophages ; Obesity ; Phosphotransferases ; Sodium Salicylate

To address a donor kidney shortage, marginal grafts have been applied in deceased donor kidney transplantation (DDKT). These grafts exhibit comparatively unfavorable outcomes, particularly when cold ischemia time (CIT) is prolonged. Hypothermic machine perfusion (HMP) has been investigated to mitigate the effects of prolonged CIT during graft transport. The present case involved successful management of the longest CIT recorded in Korea by employing HMP in DDKT. The donor was a 54-year-old man (Korean Kidney Donor Profile Index, 82%) with diabetes. The recipient, a 51-year-old man on peritoneal dialysis, had end-stage renal disease secondary to diabetic nephropathy.Following procurement, the left kidney was preserved using HMP. Inclement weather delayed graft transportation; consequently, the total CIT was 28 hours and 6 minutes, with the kidney preserved by HMP for 22 hours and 35 minutes. Postoperative graft function gradually recovered, and urine output was satisfactory. Delayed graft function was not observed, and the patient was discharged on postoperative day 13 without significant complications. Five months after surgery, his serum creatinine level was 1.7 mg/dL. Successful DDKT with a marginal donor graft via HMP, despite the longest CIT yet observed in Korea, underscores the usefulness of HMP in enhancing graft quality and preserving function.

BACKGROUND: The authors have developed a Digital image chart(DIC) and digital Radiotherapy Record System (DRRS). We have evaluated the DIC and DRRS for reliability, usefulness, ease of use, and efficiency. METHOD AND MATERIALS: The basic design o f the DIC and DRRS was to build an digital image database of radiation therapy patient records for a more efficient and timely flow of critical image in formation throughout the department. This system is a subunit of comprehensive radiation oncology managemert system (C-ROMS) and composed of a picture archiving and communication system (PACS), radiotherapy information database, and a radiotherapy imaging database. The DIC and DRRS were programmed using Delphi under a Windows 95 environment and is capable of displaying the digital images of patients identification photos, simulation films, radiotherapy setup, diagnostic radiology image... Gross lesion photos, and radiotherapy planning isodose charts with beam arrangements. Twenty-three clients in the department are connected by Ethernet (10 Mbps) to the central image server (Sun Ultra-sparc 1 workstation). RESULTS: From the introduction of this system in February 1998 through December 1999, we have accumulated a total of 15,732 individual images for 2,556 patients. We can organize radiation therapy in; paperless environment in 120 patients with breast cancer. Using this system, we have succeeded in the prompt, accurate, and simultaneous access to patient care information from multiple locations throughout the department. This coordination has resulted in improved operational efficiency within the department. CONCLUSION: The authors believe that the DIC and DRRS has contributed to the improvement of radiation oncology department efficacy as well as to time and resource savings by providing necessary visual information throughout the department conveniently and simultaneously. As a result, we can also achieve the paperless and filmless practice of radiation oncology with this system.
Breast Neoplasms ; Dacarbazine ; Hospital Information Systems ; Humans ; Income ; Patient Care ; Radiation Oncology* ; Radiotherapy*

We report a case of giant cell tumor originating from the anterior arc of the rib. The tumor and the surrounding chest wall were completely resected, and the chest wall defect was covered with Marlex mesh. Giant cell tumor of the bone usually originates from the epiphysis of long bones. Even when the tumor occur in ribs, it usually occur in the posterior aspect. However, giant cell tumor should be included in the differential diagnosis of a tumor originating from the anterior arc of the ribs.
Adult ; Bone Neoplasms/pathology/*radiography ; Diagnosis, Differential ; Giant Cell Tumor of Bone/pathology/*radiography ; Giant Cell Tumors/pathology/*radiography ; Humans ; Male ; Polypropylenes ; Ribs/pathology/*radiography ; Surgical Mesh ; Thoracic Wall/pathology/*radiography ; Tomography, X-Ray Computed

Purpose: There has been no extensive study to compare the efficacy between rituximab originator (Mabthera®) and its biosimilar (Truxima®) for microscopic polyangiitis (MPA) and granulomatosis with polyangiitis (GPA). Here, we investigated the clinical effects of rituximab on poor outcomes of MPA and GPA in Korean patients, and compared those between Mabthera® and Truxima®. Materials and Methods: We retrospectively reviewed the medical records of a total of 139 patients, including 97 MPA patients and 42 GPA patients. At diagnosis, antineutrophil cytoplasmic antibody positivity and comorbidities were assessed. During follow-up, all-cause mortality, relapse, end-stage renal disease, cerebrovascular accident and acute coronary syndrome were evaluated as poor outcomes. In this study, rituximab was used as either Mabthera® or Truxima®. Results: The median age at diagnosis was 60.1 years and 46 patients were men (97 MPA and 42 GPA patients). Among poor outcomes, patients receiving rituximab exhibited a significantly lower cumulative relapse-free survival rate compared to those not receiving rituximab (p=0.002). Nevertheless, rituximab use did not make any difference in other poor outcomes of MPA and GPA except for relapse, which might be a rebuttal to the fact that rituximab use after relapse eventually led to better prognosis. There were no significant differences in variables at diagnosis and during follow-up between patients receiving Mabthera® and those receiving Truxima®. Patients receiving Truxima® exhibited a similar pattern of the cumulative survival rates of each poor outcome to those receiving Mabthera®. Conclusion Truxima® prevents poor outcomes of MPA and GPA as effectively as does Mabthera®.

Purpose: We investigated whether antineutrophil cytoplasmic antibody (ANCA) positivity is associated with vascular manifestations at diagnosis of Behçet's disease (BD) and poor outcomes during follow-up. Materials and Methods: We retrospectively reviewed the medical records of 1060 patients with BD. Among them, 808 patients could be diagnosed with BD based on the revised version of the International Criteria for Behçet's Disease (ICBD) in 2014 (2014 ICBD criteria) and 588 patients could be diagnosed with BD based on the International Study Group (ISG) criteria proposed in 1990 (1990 ISG criteria). We examined the sites and patterns of vascular involvement in the BD patients at diagnosis and evaluated adverse outcomes during follow up, such as all-cause mortality, acute coronary syndrome, and deep vein thrombosis. Results: Among the 808 patients with BD based on the 2014 ICBD criteria, the rate of ANCA positivity at diagnosis was 2.2%. ANCA-positive BD patients exhibited a higher frequency of overall vascular manifestations (22.2% vs. 6.1%) and higher frequencies of vascular involvement in the upper extremities and visceral arteries than ANCA-negative BD patients (5.6% vs. 0.1% and 5.6% vs. 0.1%). Among the 588 BD patients based on the 1990 ISG criteria, similarly, ANCA-positive BD patients exhibited a higher frequency of vascular manifestations than ANCA-negative BD patients. ANCA positivity, however, did not seem to be associated with poor outcomes in BD patients during follow up. Conclusion ANCA positivity in BD patients was found to be associated with cross-sectional vascular involvement in the upper extremities and visceral arteries at diagnosis but was not predictive of poor outcomes during follow-up.

PURPOSE: UGT1A1, UGT2B7, and UGT2B15 are well-known pharmacogenes that belong to the uridine diphosphate glucuronyltransferase gene family. For personalized drug treatment, it is important to study differences in the frequency of core markers across various ethnic groups. Accordingly, we screened single nucleotide polymorphisms (SNPs) of these three genes and analyzed differences in their frequency among five ethnic groups, as well as attempted to predict the function of novel SNPs. MATERIALS AND METHODS: We directly sequenced 288 subjects consisting of 96 Korean, 48 Japanese, 48 Han Chinese, 48 African American, and 48 European American subjects. Subsequently, we analyzed genetic variability, linkage disequilibrium (LD) structures and ethnic differences for each gene. We also conducted in silico analysis to predict the function of novel SNPs. RESULTS: A total of 87 SNPs were detected, with seven pharmacogenetic core SNPs and 31 novel SNPs. We observed that the frequencies of UGT1A1 *6 (rs4148323), UGT1A1 *60 (rs4124874), UGT1A1 *93 (rs10929302), UGT2B7 *2 (rs7439366), a part of UGT2B7 *3 (rs12233719), and UGT2B15 *2 (rs1902023) were different between Asian and other ethnic groups. Additional in silico analysis results showed that two novel promoter SNPs of UGT1A1 -690G>A and -689A>C were found to potentially change transcription factor binding sites. Moreover, 673G>A (UGT2B7), 2552T>C, and 23269C>T (both SNPs from UGT2B15) changed amino acid properties, which could cause structural deformation. CONCLUSION: Findings from the present study would be valuable for further studies on pharmacogenetic studies of personalized medicine and drug response.
Asian Continental Ancestry Group/genetics ; European Continental Ancestry Group/genetics ; Female ; Gene Frequency/genetics ; Glucuronosyltransferase/*genetics ; Haplotypes/genetics ; Humans ; Linkage Disequilibrium/genetics ; Male ; Polymorphism, Single Nucleotide/*genetics

The tyrosine-protein kinase Tec (TEC) is a member of non-receptor tyrosine kinases and has critical roles in cell signaling transmission, calcium mobilization, gene expression, and transformation. TEC is also involved in various immune responses, such as mast cell activation. Therefore, we hypothesized that TEC polymorphisms might be involved in aspirin-exacerbated respiratory disease (AERD) pathogenesis. We genotyped 38 TEC single nucleotide polymorphisms in a total of 592 subjects, which comprised 163 AERD cases and 429 aspirin-tolerant asthma controls. Logistic regression analysis was performed to examine the associations between TEC polymorphisms and the risk of AERD in a Korean population. The results revealed that TEC polymorphisms and major haplotypes were not associated with the risk of AERD. In another regression analysis for the fall rate of forced expiratory volume in 1 second (FEV1) by aspirin provocation, two variations (rs7664091 and rs12500534) and one haplotype (TEC_BL2_ht4) showed nominal associations with FEV1 decline (p = 0.03-0.04). However, the association signals were not retained after performing corrections for multiple testing. Despite TEC playing an important role in immune responses, the results from the present study suggest that TEC polymorphisms do not affect AERD susceptibility. Findings from the present study might contribute to the genetic etiology of AERD pathogenesis.
Aspirin ; Asthma ; Calcium ; Forced Expiratory Volume ; Gene Expression ; Haplotypes ; Logistic Models ; Mast Cells ; Phosphotransferases ; Polymorphism, Genetic ; Polymorphism, Single Nucleotide ; Tyrosine

Purpose: Preclinical data indicate that response to radiotherapy (RT) depends on DNA damage repair. In this study, we investigated the role of mutations in genes related to DNA damage repair in treatment outcome after RT. Materials and Methods: Patients with solid tumor who participated in next generation sequencing panel screening using biopsied tumor tissue between October 2013 and February 2019 were reviewed and 97 patients that received RT were included in this study. Best response to RT and the cumulative local recurrence rate (LRR) were compared according to absence or presence of missense, nonsense, and frameshift mutations in ATM and/or BRCA1/2. Results: Of the 97 patients, five patients harbored mutation only in ATM, 22 in only BRCA1/2, and six in both ATM and BRCA1/2 (ATMmtBRCAmt). Propensity score matching was performed to select the control group without mutations (ATMwtBRCAwt, n=33). In total, 90 RT-treated target lesions were evaluated in 66 patients. Highest objective response rate of 80% was observed in ATMmtBRCAmt lesions (p=0.007), which was mostly durable. Furthermore, the cumulative 1-year LRR was the lowest in ATMmtBRCAmt lesions and the highest in ATMwtBRCAwt lesions (0% vs. 47.9%, p=0.008). RT-associated toxicities were observed in 10 treatments with no significant difference among the subgroups (p=0.680). Conclusion Tumors with ATM and BRCA1/2 mutations exhibited superior tumor response and local control after RT compared to tumors without these mutations. The results are hypothesis generating and suggest the need for integrating the tumor mutation profile of DNA repair genes during treatment planning.

PURPOSE: To report the results of a correlation analysis of skin dose assessed by in vivo dosimetry and the incidence of acute toxicity. This is a phase 2 trial evaluating the feasibility of intraoperative radiotherapy (IORT) as a boost for breast cancer patients. MATERIALS AND METHODS: Eligible patients were treated with IORT of 20 Gy followed by whole breast irradiation (WBI) of 46 Gy. A total of 55 patients with a minimum follow-up of 1 month after WBI were evaluated. Optically stimulated luminescence dosimeter (OSLD) detected radiation dose delivered to the skin during IORT. Acute toxicity was recorded according to the Common Terminology Criteria for Adverse Events v4.0. Clinical parameters were correlated with seroma formation and maximum skin dose. RESULTS: Median follow-up after IORT was 25.9 weeks (range, 12.7 to 50.3 weeks). Prior to WBI, only one patient developed acute toxicity. Following WBI, 30 patients experienced grade 1 skin toxicity and three patients had grade 2 skin toxicity. Skin dose during IORT exceeded 5 Gy in two patients: with grade 2 complications around the surgical scar in one patient who received 8.42 Gy. Breast volume on preoperative images (p = 0.001), ratio of applicator diameter and breast volume (p = 0.002), and distance between skin and tumor (p = 0.003) showed significant correlations with maximum skin dose. CONCLUSIONS: IORT as a boost was well-tolerated among Korean women without severe acute complication. In vivo dosimetry with OSLD can help ensure safe delivery of IORT as a boost.
Breast Neoplasms* ; Breast* ; Cicatrix ; Female ; Follow-Up Studies ; Humans ; Incidence ; Luminescence ; Mastectomy, Segmental ; Radiotherapy* ; Seroma ; Skin