BACKGROUND: Inflammation is an important underlying mechanism in the pathogenesis of atherosclerosis, and an elevated resting heart rate underlies the process of atherosclerotic plaque formation. We hypothesized an association between resting heart rate and subclinical inflammation. METHODS: Resting heart rate was recorded at baseline in the KoGES-ARIRANG (Korean Genome and Epidemiology Study on Atherosclerosis Risk of Rural Areas in the Korean General Population) cohort study, and was then divided into quartiles. Subclinical inflammation was measured by white blood cell count and high-sensitivity C-reactive protein. We used progressively adjusted regression models with terms for muscle mass, body fat proportion, and adiponectin in the fully adjusted models. We examined inflammatory markers as both continuous and categorical variables, using the clinical cut point of the highest quartile of white blood cell count (≥7,900/mm³) and ≥3 mg/dL for high-sensitivity C-reactive protein. RESULTS: Participants had a mean age of 56.3±8.1 years and a mean resting heart rate of 71.4±10.7 beats/min; 39.1% were men. In a fully adjusted model, an increased resting heart rate was significantly associated with a higher white blood cell count and higher levels of high-sensitivity C-reactive protein in both continuous (P for trend <0.001) and categorical (P for trend <0.001) models. CONCLUSION: An increased resting heart rate is associated with a higher level of subclinical inflammation among healthy Korean people.
Adiponectin ; Adipose Tissue ; Atherosclerosis ; Blood Cell Count* ; Blood Cells* ; C-Reactive Protein ; Cohort Studies ; Epidemiology ; Genome ; Heart Rate* ; Heart* ; Humans ; Inflammation ; Leukocyte Count ; Leukocytes ; Male ; Plaque, Atherosclerotic

BACKGROUND AND PURPOSE: Low-density lipoprotein (LDL) particle size is considered to be one of the more important cardiovascular risk factors, and small LDL particles are known to have atherogenic potential. The aim of this study was to determine whether LDL particle size is associated with stroke severity and functional outcome in patients with atherothrombotic stroke. METHODS: Between January 2009 and May 2011, 248 patients with first-episode cerebral infarction who were admitted to our hospital within 7 days after symptom onset were prospectively enrolled. LDL particle size was measured using the nondenaturing polyacrylamide gradient gel electrophoresis assay. Stroke severity was assessed by applying the National Institutes of Health Stroke Scale (NIHSS) at admission. Functional outcome was investigated at 3 months after the index stroke using the modified Rankin Scale (mRS), and poor functional outcome was defined as an mRS score of > or =3. RESULTS: The LDL particle size in the 248 patients was 25.9+/-0.9 nm (mean+/-SD). LDL particle size was inversely correlated with the degree of cerebral artery stenosis (p=0.010). Multinomial multivariate logistic analysis revealed that after adjustment for age, sex, and variables with p<0.1 in univariate analysis, LDL particle size was independently and inversely associated with stroke severity (NIHSS score > or =5; reference, NIHSS score 0-2; odds ratio=0.38, p=0.028) and poor functional outcome (odds ratio=0.44, p=0.038). CONCLUSIONS: The results of this study demonstrate that small LDL particles are independently correlated with stroke outcomes. LDL particle size is thus a potential biomarker for the prognosis of atherothrombotic stroke.
Atherosclerosis ; Cerebral Arteries ; Cerebral Infarction ; Constriction, Pathologic ; Electrophoresis ; Humans ; Lipoproteins ; National Institutes of Health (U.S.) ; Particle Size* ; Prognosis ; Prospective Studies ; Risk Factors ; Stroke*

BACKGROUND: The impact of HLA and KIR ligand mismatching on the outcome of hematopoietic stem cell transplantation (HSCT) remains unclear. Previous reports have identified considerable ethnic differences in the impact of HLA and KIR ligand mismatches, as well as KIR ligand status, on HSCT; however, to date, no data has been acquired in Korean adult patients. METHODS: We investigated the association of high-resolution HLA matching on five loci (HLA-A, -B, -C, -DRB1, and -DQB1), KIR ligand mismatching, and KIR ligand status on the outcome of allogeneic HSCT from unrelated donors in 154 Korean adult patients treated at Seoul National University Hospital. RESULTS: In a multivariate analysis, less than 9/10 allelic matches in five HLA loci was an independent risk factor for acute graft-versus-host disease (GVHD) (grade II to IV) (P=0.019, odds ratio [OR]=2.7). In addition, HLA-A allele mismatching was increasingly prevalent in patients with acute GVHD compared to patients without (61.9% vs. 34.5%, P=0.06). For KIR ligand status, the patient and donor combination of both C1/C1 ligands showed better event-free and overall survival than combinations with C2 ligand patients or donors (P=0.048, P=0.034, respectively) by log-rank test. CONCLUSIONS: Korean adult transplant patients with less than 9 of 10 HLA allele matches in the HLA-A, -B, -C, -DRB1, and DQB1 loci have a higher likelihood of developing acute GVHD (grade II to IV). Impact of KIR ligand status on clinical outcome should be further studied in a larger patient population.
Adolescent ; Adult ; Alleles ; Female ; Genetic Loci ; Graft vs Host Disease/etiology ; HLA Antigens/*genetics/metabolism ; *Hematopoietic Stem Cell Transplantation/adverse effects/standards ; Histocompatibility Testing ; Humans ; Kaplan-Meier Estimate ; Leukemia/mortality/therapy ; Male ; Middle Aged ; Multivariate Analysis ; Receptors, KIR/*chemistry/metabolism ; Republic of Korea ; Risk Factors ; Transplantation, Homologous ; Young Adult

Severe graft-versus-host disease (GVHD) is an often lethal complication of allogeneic hematopoietic stem cell transplantation (HSCT). The safety of clinical-grade mesenchymal stem cells (MSCs) has been validated, but mixed results have been obtained due to heterogeneity of the MSCs. In this phase I study, the safety of bone marrow-derived homogeneous clonal MSCs (cMSCs) isolated by a new subfractionation culturing method was evaluated. cMSCs were produced in a GMP facility and intravenously administered to patients who had refractory GVHD to standard treatment resulting after allogeneic HSCT for hematologic malignancies. After administration of a single dose (1x10(6) cells/kg), 11 patients were evaluated for cMSC treatment safety and efficacy. During the trial, nine patients had 85 total adverse events and the rate of serious adverse events was 27.3% (3/11 patients). The only one adverse drug reaction related to cMSC administration was grade 2 myalgia in one patient. Treatment response was observed in four patients: one with acute GVHD (partial response) and three with chronic GVHD. The other chronic patients maintained stable disease during the observation period. This study demonstrates single cMSC infusion to have an acceptable safety profile and promising efficacy, suggesting that we can proceed with the next stage of the clinical trial.
Bone Marrow ; Drug-Related Side Effects and Adverse Reactions ; Graft vs Host Disease* ; Hematologic Neoplasms ; Hematopoietic Stem Cell Transplantation ; Humans ; Mesenchymal Stromal Cells* ; Myalgia ; Population Characteristics

BACKGROUND: Forkhead box P3 (FOXP3) is an important marker of regulatory T cells. FOXP3 polymorphisms are associated with autoimmune diseases, cancers, and allograft outcomes. We examined whether single nucleotide polymorphisms (SNPs) at the FOXP3 locus are associated with clinical outcomes after allogenic hematopoietic stem cell transplantation (HSCT). METHODS: Five FOXP3 SNPs (rs5902434, rs3761549, rs3761548, rs2232365, and rs2280883) were analyzed by PCR-sequencing of 172 DNA samples from allogenic HSCT patients. We examined the relationship between each SNP and the occurrence of graft-versus-host disease (GVHD), post-HSCT infection, relapse, and patient survival. RESULTS: Patients with acute GVHD (grades II-IV) showed higher frequencies of the rs3761549 T/T genotype, rs5902434 ATT/ATT genotype, and rs2232365 G/G genotype than did patients without acute GVHD (P=0.017, odds ratio [OR]=5.3; P=0.031, OR=2.4; and P=0.023, OR=2.6, respectively). Multivariate analysis showed that the TT genotype of rs3761549 was an independent risk factor for occurrence of acute GVHD (P=0.032, hazard ratio=5.6). In contrast, the genotype frequencies of rs3761549 T/T, rs5902434 ATT/ATT, and rs2232365 G/G were lower in patients with post-HSCT infection than in patients without infection (P=0.026, P=0.046, and P=0.031, respectively). CONCLUSIONS: rs3761549, rs5902434, and rs2232365 are associated with an increased risk of acute GVHD and decreased risk of post-HSCT infection.
Allografts ; Autoimmune Diseases ; DNA ; Genotype ; Graft vs Host Disease ; Hematopoietic Stem Cell Transplantation* ; Hematopoietic Stem Cells* ; Humans ; Multivariate Analysis ; Odds Ratio ; Polymorphism, Single Nucleotide* ; Recurrence ; Risk Factors ; T-Lymphocytes, Regulatory

Toxoplasmosis is a rare but fatal complication in hematopoietic stem cell transplant recipients, usually associated with allogeneic hematopoietic stem cell transplantation (HSCT). We report a case of cerebral toxoplasmosis in a patient with multiple myeloma, following tandem autologous stem cell transplantation. A 55-year-old Korean male presented with weakness in both legs that had progressed to both arms. A magnetic resonance imaging scan of the brain revealed multiple, variable-sized ring-enhancing lesions with surrounding edema in the cerebral hemispheres and brain stem. Stereotactic biopsy revealed bradyzoites of Toxoplasma gondii in the brain tissue. The patient received trimethoprim-sulfamethoxazole, followed by pyrimethamine and sulfadiazine, accompanying treatment for progressive multiple myeloma. Cerebral toxoplasmosis should be considered as one of the differential diagnoses in patients with neurologic signs following autologous HSCT.
Arm ; Biopsy ; Brain ; Brain Stem ; Cerebrum ; Diagnosis, Differential ; Edema ; Hematopoietic Stem Cell Transplantation ; Hematopoietic Stem Cells ; Humans ; Leg ; Magnetic Resonance Imaging ; Male ; Middle Aged ; Multiple Myeloma ; Neurologic Manifestations ; Pyrimethamine ; Stem Cell Transplantation ; Stem Cells ; Sulfadiazine ; Toxoplasma ; Toxoplasmosis ; Toxoplasmosis, Cerebral ; Trimethoprim, Sulfamethoxazole Drug Combination

PURPOSE: To evaluate the effect of repeated debulking surgery for high-grade pseudomyxoma peritonei (PMP) originating from the appendix.METHODS: Between January 1998 and December 2014, fifty patients, who underwent debulking surgery for high-grade PMP originating from the appendix, were obtained from a prospectively collected database and retrospectively analyzed. Two groups according to the number of operations were divided and analyzed.RESULTS: A total of 118 operations were performed. Thirty-one patients received more than two operations. The median interval between operations was 18.2 months (range, 2–170 months). Complications developed after 26 operations (22.0%), including ileus (n=10), intra-abdominal fluid collection (n=7), surgical site infection (n=5), and others. There were two mortalities within 30 days after operation. Between two groups of patients who received one operation only and patients who received more than two operations, transfusion, diversion operation, and postoperative complication rate showed statistically significant differences. Two groups of patients had no differences in overall survival rates.CONCLUSION: Our results indicate that the number of operations does not affect the survival rate of high-grade appendiceal PMP, in which repeated debulking surgery is vital to relieve symptoms of the tumor burden.
Appendix ; Cytoreduction Surgical Procedures ; Humans ; Ileus ; Mortality ; Postoperative Complications ; Prospective Studies ; Pseudomyxoma Peritonei ; Recurrence ; Retrospective Studies ; Surgical Wound Infection ; Survival Rate ; Tumor Burden

PURPOSE: Neuroendocrine tumor is a rare tumor in the rectum, but incidence has been increasing. Local excision is an option for treatment of small tumors, and transanal excision or endoscopic resection can be undergone. But indications for local excision have not been established yet. This study was to compare the long-term oncologic outcomes between transanal excision and endoscopic resection for rectal neuroendocrine tumor.METHODS: Patients diagnosed and treated with rectal neuroendocrine tumor from 2000 to 2015 were collected prospectively, and medical records were analyzed retrospectively.RESULTS: Forty patients were included, mean age was 50.20±13.35 years (male:female=23:17). Transanal excision and endoscopic resection were performed in 28 (70%) and 12 (30%) patients, respectively. Mean tumor size was 0.63±0.37 cm, and tumor location was 5.45±1.89 cm from anal verge. Tumor location was more distal rectum in transanal excision (5.04±1.73 cm vs. 6.42±1.98 cm, P=0.049). Pathologic T stage was T1 in all patients. Most of the patients (90%) showed tumor grade 1. After median 24 months (range, 0–86 months) follow-up, one patient (2.5%) experienced local recurrence. The patient underwent further transanal excision. There was no mortality after local excision.CONCLUSION: Local excision is a safe and effective treatment for small-sized neuroendocrine tumors in rectum.
Carcinoid Tumor ; Follow-Up Studies ; Humans ; Incidence ; Medical Records ; Mortality ; Neuroendocrine Tumors ; Prospective Studies ; Rectal Neoplasms ; Rectum ; Recurrence ; Retrospective Studies

The role that children play in the transmission of the omicron variant is unclear. Here we report an outbreak that started in young children attending various pediatric facilities, leading to extensive household transmission that affected 75 families with 88 confirmed case-patients in 3 weeks. Tailored social and public health measures directed towards children and pediatric facilities are warranted with the emergence of highly transmissible omicron variant to mitigate the impact of coronavirus diseases 2019 (COVID-19).

Purpose: Globally, chronic kidney disease (CKD) is common and has been associated with an increased risk of colorectal cancer (CRC). There is a dearth of literature on the real-world morbidity and mortality associated with CKD comorbid with CRC. This study was performed to evaluate real-world survival outcomes of colorectal malignancy in Korean CKD patients. Methods: The National Health Insurance Service of Korea provided data on patients who underwent surgical resection among patients diagnosed with CRC from 2002 to 2019. Results: A total of 219,550 patients were included: 6,181 patients with underlying CKD and 213,369 patients without it.Each morbidity was significantly higher in the CKD-CRC group, and the postoperative mortality rates for the 30-day (3.11% vs. 1.78%, P < 0.001), 60-day (5.95% vs. 3.83%, P < 0.001), and 90-day mortality rate (8.12% vs. 5.32%, P < 0.001) were significantly higher in the CKD group. The median survival time (MST, year) was significantly lower in the CKD-CRC group (5.63; interquartile range [IQR], 5.26–5.91) than in the non-CKD-CRC group (8.71; IQR, 8.37–8.93). MST was significantly lower among CKD patients who received chemotherapy after adjustment by multivariate analysis (adjusted hazard ratio [HR], 1.43; 95% confidence interval [CI], 1.37–1.49; P < 0.001]). Subgroup analysis showed that in the CKD-CRC group, MST was lower in patients who received dialysis than in those who did not, even after multivariate analysis (adjusted HR, 2.38;95% CI, 2.20–2.58; P < 0.001). Conclusion Prevention of CKD-to-end-stage renal disease progression should be adopted as a strategy to increase postoperative survival, along with active surveillance and cancer treatment.