Background/Aims: The prognostic significance of 18F-fluorodeoxyglucose (FDG)-positron emission tomography-computed tomography (PET/CT) in peripheral T-cell lymphomas (PTCLs) are controversial. We explored the prognostic impact of sequential 18F-FDG PET/CT during frontline chemotherapy of patients with PTCLs. Methods: In total, 143 patients with newly diagnosed PTCLs were included. Sequential 18F-FDG PET/CTs were performed at the time of diagnosis, during chemotherapy, and at the end of chemotherapy. The baseline total metabolic tumor volume (TMTV) was calculated using the the standard uptake value with a threshold method of 2.5. Results: A baseline TMTV of 457.0 cm3 was used to categorize patients into high and low TMTV groups. Patients with a requirehigh TMTV had shorter progression-free survival (PFS) and overall survival (OS) than those with a low TMTV (PFS, 9.8 vs. 26.5 mo, p = 0.043; OS, 18.9 vs. 71.2 mo, p = 0.004). The interim 18F-FDG PET/CT response score was recorded as 1, 2–3, and 4–5 according to the Deauville criteria. The PFS and OS showed significant differences according to the interim 18F-FDG PET/CT response score (PFS, 120.7 vs. 34.1 vs. 5.1 mo, p < 0.001; OS, not reached vs. 61.1 mo vs. 12.1 mo, p < 0.001). Conclusions The interim PET/CT response based on visual assessment predicts disease progression and survival outcome in PTCLs. A high baseline TMTV is associated with a poor response to anthracycline-based chemotherapy in PTCLs. However, TMTV was not an independent predictor for PFS in the multivariate analysis.

Purpose: Fluorodeoxyglucose positron emission tomography–computed tomography (PET-CT) is gaining evidence as a predictive factor in non-small cell lung cancer (NSCLC). Stereotactic ablative radiotherapy (SABR) is the standard treatment in early-stage NSCLC when a patient is unsuitable for surgery. We performed a study to assess the prognostic clinical significance of PET-CT after SABR in early-stage NSCLC. Materials and Methods: Seventy-six patients with stage I NSCLC treated with SABR were investigated. Total radiation dose ranged from 36 to 63 Gy in three to eight fractions depending on tumor location and size. Respiratory motion control was implemented at simulation and during treatment. PET-CT prior to SABR was performed in 66 patients (86.8%). Results: Median follow-up time was 32 months (range, 5 to 142 months). Local control rate at 1, 2, and 5 years were 95.9%, 92.8%, and 86.7%, respectively. Overall survival (OS) at 1, 2, and 5 years were 91.0%, 71.3%, and 52.1% respectively. Cause-specific survival at 1, 2, and 5 years were 98.6%, 93.1%, and 84.3% respectively. Tumor size and pre-SABR maximal standardized uptake value (SUVmax) demonstrated statistical significance in the Kaplan-Meier survival analyses with log-rank test. In multivariate analyses pre-SABR SUVmax remained statistically significant in correlation to OS (p=0.024; hazard ratio [HR], 3.2; 95% confidence interval [CI], 1.2 to 8.8) and with marginal significance in regards to regional progression-free survival (p=0.059; HR, 32.5; 95% CI, 2.6 to 402.5). Conclusion Pre-SABR SUVmax demonstrated a predictive power in statistical analyses. Tumors with SUVmax above 6 at diagnosis were associated with inferior outcomes.

Background/Aims: Low-level viremia (LLV) after nucleos(t)ide analog treatment was presented as a possible cause of hepatocellular carcinoma (HCC) in patients with chronic hepatitis B (CHB). However, detailed information on patients’ adherence in the real world was lacking. This study aimed to evaluate the effects of LLV on HCC development, mortality, and cirrhotic complications among patients according to their adherence to entecavir (ETV) treatment. Methods: We performed a retrospective observational analysis of data from 894 consecutive adult patients with treatment-naïve CHB undergoing ETV treatment. LLV was defined according to either persistent or intermittent episodes of <2,000 IU/mL detectable hepatitis B virus DNA during the follow-up period. Good adherence to medication was defined as a cumulative adherence ≥90% per study period. Results: Without considering adherence in the entire cohort (n=894), multivariate analysis of the HCC incidence showed that LLV was an independent prognostic factor in addition to other traditional risk factors in the entire cohort (P=0.031). Good adherence group comprised 617 patients (69.0%). No significant difference was found between maintained virologic response and LLV groups in terms of the incidence of liver-related death or transplantation, HCC, and hepatic decompensation in good adherence group, according to multivariate analyses. Conclusions In patients with treatment-naïve CHB and good adherence to ETV treatment in the real world, LLV during treatment is not a predictive factor for HCC and cirrhotic complications. It may be unnecessary to adjust their antiviral agent for patients with good adherence who experience LLV during ETV treatment.

Legionella species are abundant in the built environment and are increasingly recognized as a cause of Legionnaires' disease (LD). As the number of cases of Legionnaires' disease acquired by local communities in the Seoul metropolitan area in Korea has been increased, there was concern that changes in environmental factors could affect disease outbreaks. We described the association between climatic variables and occurrence of legionellosis in Korea and Legionella detection rate in Seoul area. A total of 418 cases of legionellosis were reported between 2014 and 2017. There was a seasonal peak in summer. LD continuously occurred from early spring to winter every year and rapidly increased in summer. In the regression analysis, the primary variables of interest- PM2.5 (µg/m³), NO₂ (ppb), and a number of the date of issue O₃ warning were not significant except for average temperature (R²=0.8075). The Legionella detection rate in Seoul, Korea showed a trend similar to precipitation (P=0.708, ANOVA). A relatively high proportion of Legionella detection rate was shown, especially cooling tower (17.7%) and public bath (19.3%). This finding is in line with current understanding of the ecological profile of this pathogen and supports the assertion that legionellosis occurs through contamination of water sources.
Baths ; Disease Outbreaks ; Epidemiology ; Korea ; Legionella ; Legionellosis ; Legionnaires' Disease ; Regression Analysis ; Seasons ; Seoul ; Water

Vulvar squamous cell carcinoma (SCC) consists of two different etiologic categories: human papilloma virus (HPV)-associated (HPV (+)) and HPV-non-associated (HPV (−)). There have been no genome-wide studies on the genetic alterations of vulvar SCCs or on the differences between HPV (+) and HPV (−) vulvar SCCs. In this study, we performed whole-exome sequencing and copy number profiling of 6 HPV (+) and 9 HPV (−) vulvar SCCs and found known mutations (TP53, CDKN2A and HRAS) and copy number alterations (CNAs) (7p and 8q gains and 2q loss) in HPV (−) SCCs. In HPV (+), we found novel mutations in PIK3CA, BRCA2 and FBXW7 that had not been reported in vulvar SCCs. HPV (−) SCCs exhibited more mutational loads (numbers of nonsilent mutations and driver mutations) than HPV (+) SCCs, but the CNA loads and mutation signatures between HPV (+) and HPV (−) SCCs did not differ. Of note, 40% and 40% of the 15 vulvar SCCs harbored PIK3CA and FAT1 alterations, respectively. In addition, we found that the SCCs harbored kataegis (a localized hypermutation) in 2 HPV (+) SCCs and copy-neutral losses of heterozygosity in 4 (one HPV (+) and 3 HPV (−)) SCCs. Our data indicate that HPV (+) and HPV (−) vulvar SCCs may have different mutation and CNA profiles but that there are genomic features common to SCCs. Our data provide useful information for both HPV (+) and HPV (−) vulvar SCCs and may aid in the development of clinical treatment strategies.

BACKGROUND: A subanalysis study of the ENGAGE AF-TIMI 48 trial showed that cardiac troponin I, N-terminal proB-type natriuretic peptide, and D-dimer, were powerful predictors of cerebrovascular adverse events. We aimed to evaluate D-dimer and cardiac troponin I levels during the acute period of ischemic stroke in anticoagulation-naïve patients with non-valvular atrial fibrillation (NVAF) and also studied the association between these biomarkers and stroke severity. METHODS: Consecutive anticoagulation-naïve patients with acute ischemic stroke due to NVAF were enrolled within two days after each stroke event, and all patients were stratified into either moderate-to-severe or mild neurologic deficit groups using the National Institutes of Health Stroke Scale (NIHSS) at admission. RESULTS: A total of 98 patients were enrolled in this study. The median value for the D-dimer was above the upper limit of the normal reference range, but the troponin I value was within the normal range for all patients. After adjusting for CHA2DS2-VASc risk factors, the log-transformed values for D-dimer were positively correlated with an increasing NIHSS score (r=0.233; P=0.051). In the multivariate logistic analysis, the log-transformed D-dimer was positively associated with more severe strokes (odds ratio, 30.1; 95% confidence interval [CI], 1.9–486.2 and 29.7; 95% CI, 2.0–430.8 in the upper two quartiles respectively). The log-transformed values for troponin I did not correlate with the NIHSS score. CONCLUSION: D-dimer levels were higher and an independent risk factor for severe stroke in anticoagulation-naïve patients with NVAF related stroke. In contrast, troponin I levels were normal and were not associated with stroke severity.
Atrial Fibrillation ; Biomarkers ; Humans ; National Institutes of Health (U.S.) ; Neurologic Manifestations ; Reference Values ; Risk Factors ; Stroke ; Troponin I

PURPOSE: Genexol-PM is a Cremophor EL–free formulation of low-molecular-weight, non-toxic, and biodegradable polymeric micelle-bound paclitaxel. We conducted a phase III study comparing the clinical efficacy and toxicity of Genexol-PM with conventional paclitaxel (Genexol). MATERIALS AND METHODS: Patients were randomly assigned (1:1) to receive Genexol-PM 260 mg/m² or Genexol 175 mg/m² intravenously every 3 weeks. The primary outcome was the objective response rate (ORR). RESULTS: The study enrolled 212 patients, of whom 105 were allocated to receive Genexol-PM. The mean received dose intensity of Genexol-PM was 246.8±21.3 mg/m² (95.0%), and that of Genexol was 168.3±10.6 mg/m² (96.2%). After a median follow-up of 24.5 months (range, 0.0 to 48.7 months), the ORR of Genexol-PM was 39.1% (95% confidence interval [CI], 31.2 to 46.9) and the ORR of Genexol was 24.3% (95% CI, 17.5 to 31.1) (p(non-inferiority)=0.021, p(superiority)=0.016). The two groups did not differ significantly in overall survival (28.8 months for Genexol-PM vs. 23.8 months for Genexol; p=0.52) or progression-free survival (8.0 months for Genexol-PM vs. 6.7 months for Genexol; p=0.26). In both groups, the most common toxicities were neutropenia, with 68.6% occurrence in the Genexol-PM group versus 40.2% in the Genexol group (p < 0.01). The incidences of peripheral neuropathy of greater than grade 2 did not differ significantly between study treatments. CONCLUSION: Compared with standard paclitaxel, Genexol-PM demonstrated non-inferior and even superior clinical efficacy with a manageable safety profile in patients with metastatic breast cancer.
Breast Neoplasms* ; Breast* ; Disease-Free Survival ; Follow-Up Studies ; Humans ; Incidence ; Neutropenia ; Paclitaxel* ; Peripheral Nervous System Diseases ; Polymers* ; Treatment Outcome

PURPOSE: Neuroinflammation is mediated by activation of microglia implicated in the pathogenesis of neurodegenerative disorders such as Alzheimer's disease and Parkinson's disease. Inhibition of neuroinflammation may be an effective solution to treat these brain disorders. Petalonia binghamiae is known as a traditional food, based on multiple biological activities such as anti-oxidant and anti-obesity. In present study, the anti-neuroinflammatory potential of Petalonia binghamiae was investigated in LPS-stimulated BV2 microglial cells. METHODS: Cell viability was measured by MTT assay. Production of nitric oxide (NO) was examined using Griess reagent. Expression of inducible NO synthase (iNOS) and cyclooxygenase-2 (COX-2) was detected by Western blot analysis. Activation of nuclear factor κB (NF-κB) signaling was examined by nuclear translocation of NF-κB p65 subunit and phosphorylation of IκB. RESULTS: Extract of Petalonia binghamiae significantly inhibited LPS-stimulated NO production and iNOS/COX-2 protein expression in a dose-dependent manner without cytotoxicity. Pretreatment with Petalonia binghamiae suppressed LPS-induced NF-κB p65 nuclear translocation and phosphorylation of IκB. Co-treatment with Petalonia binghamiae and pyrrolidine duthiocarbamate (PDTC), an NF-κB inhibitor, reduced LPS-stimulated NO release compared to that in PB-treated or PDTC-treated cells. CONCLUSION: The present results indicate that extract of Petalonia binghamiae exerts anti-neuroinflammation activities, partly through inhibition of NF-κB signaling. These findings suggest that Petalonia binghamiae might have therapeutic potential in relation to neuroinflammation and neurodegenerative diseases.
Alzheimer Disease ; Blotting, Western ; Brain Diseases ; Cell Survival ; Cyclooxygenase 2 ; Microglia ; Neurodegenerative Diseases ; Nitric Oxide ; Nitric Oxide Synthase ; Parkinson Disease ; Phosphorylation

The effect of clonidine administered intrathecally (i.t.) on the mortality and the blood glucose level induced by sepsis was examined in mice. To produce sepsis, the mixture of D-galactosamine (GaLN; 0.6 g/10 ml)/lipopolysaccharide (LPS; 27 µg/27 µl) was treated intraperitoneally (i.p.). The i.t. pretreatment with clonidine (5 µg/5 µl) increased the blood glucose level and attenuated mortality induced by sepsis in a dose-dependent manner. The i.t. post-treatment with clonidine up to 3 h caused an elevation of the blood glucose level and protected sepsis-induced mortality, whereas clonidine post-treated at 6, 9, or 12 h did not affect. The pre-treatment with oral D-glucose for 30 min prior to i.t. post-treatment (6 h) with clonidine did not rescue sepsis-induced mortality. In addition, i.t. pretreatment with pertussis toxin (PTX) reduced clonidine-induced protection against mortality and clonidine-induced hyperglycemia, suggesting that protective effect against sepsis-induced mortality seems to be mediated via activating PTX-sensitive G-proteins in the spinal cord. Moreover, pretreatment with clonidine attenuated the plasma tumor necrosis factor α (TNF-α) induced by sepsis. Clonidine administered i.t. or i.p. increased p-AMPKα1 and p-AMPKα2, but decreased p-Tyk2 and p-mTOR levels in both control and sepsis groups, suggesting that the up-regulations of p-AMPKα1 and p-AMPKα2, or down-regulations of p-mTOR and p-Tyk2 may play critical roles for the protective effect of clonidine against sepsis-induced mortality.
Animals ; Blood Glucose ; Clonidine ; Glucose ; GTP-Binding Proteins ; Hyperglycemia ; Mice ; Mortality* ; Pertussis Toxin ; Plasma ; Sepsis ; Spinal Cord* ; Tumor Necrosis Factor-alpha

The most common manifestation of multiple endocrine neoplasia type 1 (MEN1) is hyperparathyroidism. Treatment of hyperparathyroidism in MEN patients is surgical removal of the parathyroid glands, however ectopic parathyroid gland is challenging for treatment. A 51-year-old female, the eldest of 3 MEN1 sisters, had hyperparathyroidism with ectopic parathyroid adenoma in the mediastinal para-aortic region, which was detected by technetium-99m (Tc-99m) sestamibi scintigraphy and single-photon emission computed tomography/computed tomography (SPECT/CT). She underwent total parathyroidectomy with video-assisted thoracoscopic surgery on an anterior mediastinal mass. Anterior mediastinal parathyroid adenoma in MEN1 patients is rare. Precise localization of an ectopic parathyroid gland with Tc-99m sestamibi SPECT/CT can lead to successful treatment of hyperparathyroidism. This is the first reported case in the literature of mediastinal parathyroid adenoma in MEN1 patient visualized by Tc-99m sestamibi SPECT/CT.
Female ; Humans ; Hyperparathyroidism ; Male ; Middle Aged ; Multiple Endocrine Neoplasia Type 1* ; Multiple Endocrine Neoplasia* ; Parathyroid Glands ; Parathyroid Neoplasms* ; Parathyroidectomy ; Radionuclide Imaging ; Siblings ; Thoracic Surgery, Video-Assisted ; Tomography, Emission-Computed, Single-Photon