Gene-environment interactions related to blood pressure traits in two community-based Korean cohorts.

Hypertension is a complex disorder caused by genetic and environmental risk factors. Recently, genome-wide association studies (GWASs) identified more than 100 genetic variants for blood pressure traits and hypertension. However, the interactions between these genetic variants and environmental factors have not been systematically investigated. Therefore, we examined the interaction between genetic and environmental risk factors in blood pressure traits using the genetic risk score (GRS). Two Korean community-based cohorts, Cohort I (KARE; N = 8,840) and Cohort II (CAVAS; N = 9,599), were used for this study, and GRSs were calculated from 42 GWAS single-nucleotide polymorphisms (SNPs) that were validated for their association in these cohorts. We calculated GRSs in both ways by considering the effect sizes of each SNP (weighted GRS) and not considering the effect sizes (unweighted GRS). The unweighted GRS was strongly associated with systolic blood pressure, diastolic blood pressure, and hypertension (p = 9.03 × 10 -47 , p = 9.41 × 10 -48 , and p = 3.22 × 10 -55 by meta-analysis, respectively) and the weighted GRS showed the similar results. The environmental factors of body mass index, waist circumference, and drinking status were significantly associated with blood pressure traits, and the interaction between these factors and GRSs were examined. However, no interactions were found with either the GRS or the individual SNPs considered for the GRS. Our findings show that it is challenging to find GRS-environment interactions regarding blood pressure traits.

Real-world effectiveness of long-acting injections for reducing recurrent hospitalizations in patients with schizophrenia.

BACKGROUND: The comparative effectiveness of antipsychotic long-acting injections (LAIs) and oral medication is not clear due to various methodological problems. METHODS: To compare the effectiveness of LAIs and oral antipsychotics in preventing readmission in patients with schizophrenia, we performed a within-subject analysis of data collected from 75,274 patients hospitalized with schizophrenia over a 10-year period (2008-2017). Readmission rates were compared according to medication status (non-medication, oral medication alone, and LAI medication). Each admission episodes were compared according to medication status before admission. RESULTS: Total 132,028 episodes of admission were analyzed. During 255,664 person-years of total observation, 101,589 outcome events occurred. Comparing LAI to only oral medication, IRR was 0.71 (0.64-0.78, P < 0.001). IRR of LAI to only oral medication of first index admission was 0.74 (0.65-0.86). As hospitalization was repeated, IRR of second, third, and fourth or more index admission decreased 0.65 (0.53-0.79), 0.56 (0.43-0.76), and 0.42 (0.31-0.56), respectively. CONCLUSIONS: LAI treatment reduced the readmission rate by 29% compared with oral medication in real-world settings. Moreover, LAIs reduced the readmission rate by 58% in patients with repeated admissions. The more readmissions, the greater the effect of LAIs in reducing the risk of re-hospitalization compared with oral antipsychotics.

GAREM1 regulates the PR interval on electrocardiograms.

PR interval is the period from the onset of P wave to the start of the QRS complex on electrocardiograms. A recent genomewide association study (GWAS) suggested that GAREM1 was linked to the PR interval on electrocardiograms. This study was designed to validate this correlation using additional subjects and examined the function of Garem1 in a mouse model. We analyzed the association of rs17744182, a variant in the GAREM1 locus, with the PR interval in 5646 subjects who were recruited from 2 Korean replication sets, Yangpyeong (n = 2471) and Yonsei (n = 3175), and noted a significant genomewide association by meta-analysis (P = 2.39 × 10-8). To confirm the function of Garem1 in mice, Garem1 siRNA was injected into mouse tail veins to reduce the expression of Garem1. Garem1 transcript levels declined by 53% in the atrium of the heart (P = 0.029), and Garem1-siRNA injected mice experienced a significant decrease in PR interval (43.27 ms vs. 44.89 ms in control, P = 0.007). We analyzed the expression pattern of Garem1 in the heart by immunohistology and observed specific expression of Garem1 in intracardiac ganglia. Garem1 was expressed in most neurons of the ganglion, including cholinergic and adrenergic cells. We have provided evidence that GAREM1 is involved in the PR interval of ECGs. These findings increase our understanding of the regulatory signals of heart rhythm through intracardiac ganglia of the autonomic nervous system and can be used to guide the development of a therapeutic target for heart conditions, such as atrial fibrillation.

Real-world treatment patterns for patients 80 years and older with early lung cancer: a nationwide claims study.

BACKGROUND: Old age is an important factor that could affect the treatment of early-stage lung cancer. In this study, we evaluated the treatment patterns and outcomes of patients over the age of 80 years who had been diagnosed with early-stage lung cancer in real-world practice. METHODS: Elderly patients who were diagnosed with early-stage lung cancer between 2008 and 2016 were identified using claims data provided by the Health Insurance Review and Assessment Service. The proportion of patients who underwent surgical resection or stereotactic body radiation therapy (SBRT), practice pattern trends, and overall survival (OS) were analyzed from the population-based data. RESULTS: Over 9 years, 1,684 patients underwent surgical resection (74.9%) or SBRT (25.1%) as a localized treatment. From 2008 to 2016, the treatment modality changed: the percentage of patients who underwent surgical resection decreased from 90.6 to 71.4%, and those who underwent SBRT increased from 9.4 to 28.6%. The percentage of patients treated with SBRT increased over time (p < 0.001). The median OS was 56.4 months in the surgery group and 35.5 months in the SBRT group. The SBRT group showed worse OS compared with the surgery group (Adjusted hazard ratio, 1.44; 95% confidence interval, 1.21-1.72; p < 0.001). CONCLUSION: Changes in local treatment patterns in elderly lung cancer patients were observed and SBRT increased its role in this population. Surgical resection or SBRT should be considered the treatment of choice in elderly patients with localized lung cancer. Further prospective studies are required to elucidate the benefits of surgery and SBRT.

The Value of Preoperative Positron Emission Tomography/Computed Tomography in Node-Negative Endometrial Cancer on Magnetic Resonance Imaging.

OBJECTIVE: The aim of this study was to investigate the value of [18F]fluorodeoxyglucose-positron emission tomography/computed tomography (FDG-PET/CT) in predicting lymph node status in node-negative endometrial cancer on preoperative magnetic resonance imaging (MRI). METHODS: Patients with endometrial cancer who underwent both preoperative MRI and FDG-PET/CT followed by hysterectomy and lymphadenectomy were initially included. We then enrolled patients with MRI-defined node-negative disease (lymph nodes <1 cm in the short-axis diameter, or no visible lymph node). Histologic examination was the gold standard for lymph node metastasis diagnosis. The diagnostic performance of FDG-PET/CT in predicting lymph node metastasis was calculated in patient-by-patient and lymph node station-by-station analyses. RESULTS: On preoperative MRI, 362 patients had no lymph node metastasis. All patients underwent pelvic lymph node dissection and 118 patients underwent further para-aortic lymph node dissection. From 2099 lymph node stations, 10,238 lymph nodes were retrieved. Twenty-seven patients (7.5%) had lymph node metastasis in 49 lymph node stations (2.3%) on pathologic examination. FDG-PET/CT identified lymph node metastasis in five patients (18.5%) and eight lymph node stations (16.3%). The median diameter of false-negative metastatic lymph nodes was 6 mm (range 1-22) in the long axis and 3 mm (range 1-11) in the short axis. For para-aortic lymph nodes, FDG-PET/CT diagnosed 2 of 11 patients (18.1%) with para-aortic lymph node metastasis, and 3 of 12 para-aortic lymph node stations (25%) with metastasis. CONCLUSION: Preoperative FDG-PET/CT has low value in predicting lymph node metastasis in node-negative endometrial cancer on preoperative MRI.

Serum anti-Müllerian hormone levels decrease after endometriosis surgery.

The purpose of this study was to evaluate and compare the post-operative decline in serum AMH levels in patients with endometriosis and other benign cysts. This study also attempts to clarify the factors of endometriosis that may influence the AMH level. A total of 75 were recruited prospectively between 2011 and 2012. Fifty-nine patients had endometriosis, while the other 16 had another kind of benign ovarian cyst. In the endometriosis group, the AMH level decreased significantly from pre- to postoperatively (4.3 ± 0.4 vs. 2.8 ± 0.2, p<.001). This significant decrement in AMH levels was present in the endometriosis group regardless of multiplicity (p=.028 vs. p<.001) and bilaterality (p=.003 vs. p<.001). The stage III-IV endometriosis group also demonstrated a significant decrease (p<.001). Laparoscopic ovarian cystectomy in patients with endometriosis may cause a decrease in serum AMH levels. We suggest that preoperative and postoperative AMH levels should be evaluated in reproductive-aged women with endometriosis for their future fertility.

Histogram Analysis of Apparent Diffusion Coefficients for Occult Tonsil Cancer in Patients with Cervical Nodal Metastasis from an Unknown Primary Site at Presentation.

PURPOSE: To explore the added value of histogram analysis of apparent diffusion coefficient (ADC) values over magnetic resonance (MR) imaging and fluorine 18 ((18)F) fluorodeoxyglucose (FDG) positron emission tomography (PET)/computed tomography (CT) for the detection of occult palatine tonsil squamous cell carcinoma (SCC) in patients with cervical nodal metastasis from a cancer of an unknown primary site. MATERIALS AND METHODS: The institutional review board approved this retrospective study, and the requirement for informed consent was waived. Differences in the bimodal histogram parameters of the ADC values were assessed among occult palatine tonsil SCC (n = 19), overt palatine tonsil SCC (n = 20), and normal palatine tonsils (n = 20). One-way analysis of variance was used to analyze differences among the three groups. Receiver operating characteristic curve analysis was used to determine the best differentiating parameters. The increased sensitivity of histogram analysis over MR imaging and (18)F-FDG PET/CT for the detection of occult palatine tonsil SCC was evaluated as added value. RESULTS: Histogram analysis showed statistically significant differences in the mean, standard deviation, and 50th and 90th percentile ADC values among the three groups (P < .0045). Occult palatine tonsil SCC had a significantly higher standard deviation for the overall curves, mean and standard deviation of the higher curves, and 90th percentile ADC value, compared with normal palatine tonsils (P < .0167). Receiver operating characteristic curve analysis showed that the standard deviation of the overall curve best delineated occult palatine tonsil SCC from normal palatine tonsils, with a sensitivity of 78.9% (15 of 19 patients) and a specificity of 60% (12 of 20 patients). The added value of ADC histogram analysis was 52.6% over MR imaging alone and 15.8% over combined conventional MR imaging and (18)F-FDG PET/CT. CONCLUSION: Adding ADC histogram analysis to conventional MR imaging can improve the detection sensitivity for occult palatine tonsil SCC in patients with a cervical nodal metastasis originating from a cancer of an unknown primary site.

The Risk Factors and Pregnancy Outcomes of 48 Cases of Heterotopic Pregnancy from a Single Center.

The purpose of this study was to investigate risk factors that are associated with heterotopic pregnancy (HP) following in vitro fertilization (IVF)-embryo transfer (ET) and to demonstrate the outcomes of HP after the surgical treatment of ectopic pregnancies. Forty-eight patients from a single center, who were diagnosed with HP between 1998 and 2012 were included. All of the patients had received infertility treatments, such as Clomid with timed coitus (n = 1, 2.1%), superovulation with intrauterine insemination (n = 7, 14.6%), fresh non-donor IVF-ET (n = 33, 68.8%), and frozen-thawed cycles (n = 7, 14.6%). Eighty-four additional patients were randomly selected as controls from the IVF registry database. HP was diagnosed at 7.5 ± 1.2 weeks (range 5.4-10.3) gestational age. In six cases (12.5%), the diagnosis was made three weeks after the patients underwent treatment for abortion. There were significant differences in the history of ectopic pregnancy (22.5% vs. 3.6%, P = 0.002). There were no significant differences in either group between the rates of first trimester intrauterine fetal loss (15.0% vs. 13.1%) or live birth (80.0% vs. 84.1%) after the surgical treatment for ectopic pregnancy. The risk factors for HP include a history of ectopic pregnancy (OR 7.191 [1.591-32.513], P = 0.010), abortion (OR 3.948 [1.574-9.902], P = 0.003), and ovarian hyperstimulation syndrome (OHSS) (OR 10.773 [2.415-48.060], P = 0.002). In patients undergoing IVF-ET, history of ectopic pregnancy, abortion, and OHSS may be risk factors for HP as compared to the control group of other IVF patients. The surgical treatment of HP does not appear to affect the rates of first trimester fetal loss or live birth.

Correlation between the serum luteinizing hormone to folliclestimulating hormone ratio and the anti-Müllerian hormone levels in normo-ovulatory women.

Serum anti-Müllerian hormone (AMH) levels are regarded as an age-specific marker for predicting the ovarian reserve in women of reproductive age. Some studies have shown that the luteinizing hormone (LH)/follicle stimulating hormone (FSH) ratio can be used as a predictor of ovarian reserve. The purpose of this study was to assess the variation of LH/FSH ratio with aging and to evaluate the correlation between serum LH/FSH ratio and AMH levels as a predictor of the ovarian reserve in normo-ovulatory women. We retrospectively analyzed the day 3 serum hormone levels in 1,251 patients (age range: 20-50 yr) between January 2010 and January 2011. We divided the patients into 6 groups according to their age. Relation between serum AMH level and LH/FSH ratio was analyzed statistically. The serum AMH level was inversely correlated with age (r = -0.400, P < 0.001). A significant negative correlation was found between serum LH/FSH ratio and age (r = -0.213, P < 0.001). There was a significant partial correlation between serum LH/FSH ratio and AMH level when adjusted by age (r = 0.348, P < 0.001). The LH/FSH ratio could be considered as a useful marker for the ovarian reserve and could be applied to the clinical evaluation with AMH.

Detection of internal mammary lymph node metastasis with (18)F-fluorodeoxyglucose positron emission tomography/computed tomography in patients with stage III breast cancer.

PURPOSE: The present study assessed the positive predictive value (PPV) of (18)F-fluorodeoxyglucose (FDG) positron emission tomography/computed tomography (PET/CT) for the detection of internal mammary node (IMN) metastasis in patients with clinical stage III breast cancer. METHODS: Patients who were diagnosed with clinical stage III breast cancer and underwent pretreatment (18)F-FDG PET/CT were retrospectively analyzed. The (18)F-FDG PET/CT scans were prospectively reviewed by two board-certified nuclear medicine physicians in a blinded manner. The intensities of IMNs were graded into four categories (no activity and lower, similar, and higher activities than that of the mediastinal blood pool). IMNs were measured from the combined CT (largest diameter of the short axis). Histologic data of the IMNs were obtained by ultrasonography-guided fine-needle aspiration biopsy or surgical excision. The PPV was calculated for pathologically confirmed IMNs. Visual grade, maximum standardized uptake values (SUVmax), and sizes were analyzed according to the pathology results. RESULTS: There were 249 clinical stage III breast cancer patients (age 48.0 ± 10.1 years, range 26-79 years) who had undergone initial (18)F-FDG PET/CT prior to treatment. Excluding 33 cases of stage IV breast cancer, 62 of 216 patients had visible IMNs on (18)F-FDG PET/CT, and histologic confirmation was obtained in 31 patients. There were 27 metastatic and four nonmetastatic nodes (PPV 87.1%). Metastatic nodes mostly presented with visual grade 3 (83.9%), and SUVmax and size were 3.5 ± 4.3 and 5.6 ± 2.0 mm, respectively. CONCLUSION: (18)F-FDG PET/CT has a high PPV for IMN metastasis in clinical stage III breast cancer, indicating the possibility of metastasis in IMNs with FDG uptake similar to/lower than that of the blood pool or small-sized nodes.

Usefulness of adding SPECT/CT to 99mTc-hexamethylpropylene amine oxime (HMPAO)-labeled leukocyte imaging for diagnosing prosthetic joint infections.

OBJECTIVE: This study evaluated the usefulness of adding single-photon emission computed tomography (SPECT)/computed tomography (CT) (SPECT/CT) to technetium Tc 99m (Tc) hexamethylpropylene amine oxime (HMPAO)-labeled leukocyte imaging for diagnosing infections in hip or knee joint prostheses. METHODS: The Tc-HMPAO-labeled leukocyte scans of 164 patients (71 with hip prostheses and 93 with knee prostheses) with clinically suspected prosthetic infections were reviewed retrospectively. Planar images were taken 4 to 6 and 21 to 26 hours after injecting the labeled leukocytes and SPECT/CT images were obtained 4 to 6 hours after the injection. The final diagnosis of infection was based on pathologic findings (n = 70), bacteriological data (n = 61), or clinical follow-up (n = 33). RESULTS: Of the 164 patients, 89 patients had a diagnosis of prosthetic joint infections. The sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and diagnostic accuracy of the planar images alone were 82.0%, 88.0%, 89.0%, 80.5%, and 84.8%, respectively. When the planar images were combined with SPECT, the sensitivity, specificity, PPV, NPV, and diagnostic accuracy were 91.0%, 88.0%, 90.0%, 89.2%, and 89.6%, respectively. When the planar images were combined with SPECT/CT, these values increased further to 93.3%, 93.3%, 94.3%, 92.1%, and 93.3%, respectively. Adding CT to SPECT resulted in a greater increase in sensitivity and specificity for hip prosthesis infections than for knee prosthesis infections. SPECT/CT mainly contributed by precisely localizing the anatomical site of the active inflammatory lesion and by delineating the extent of the lesion after diagnosis with SPECT. CONCLUSIONS: Single-photon emission computed tomography/CT combined with Tc-HMPAO-labeled leukocyte imaging was useful for diagnosing prosthesis infections, particularly in hip prosthesis infections, as it improved diagnostic accuracy and provided anatomical localization data.

Evaluation of selective positron emission tomography template method for spatial normalization of amyloid imaging with 11C-Pittsburgh Compound B.

OBJECTIVE: Spatial normalization of C-Pittsburgh Compound B (PiB) images is challenging for an automatic quantitative analysis without magnetic resonance imaging (MRI) because of different distribution patterns between amyloid positive and negative images. To overcome this issue, we evaluated a selective positron emission tomography template (SPT) method. MATERIALS AND METHODS: Three sets of single positron emission tomography templates were created: PiB negative template, PiB positive template, and mixed template. Sixty-one patients with dementia were enrolled as the validation cohort. Magnetic resonance imaging-aided normalization method was used as a reference. The SPT method was based on visual classification (positive, negative, and equivocal). The optimal templates for each visual group were determined by correlation values and average percent errors (APEs) with MRI-aided normalization. The results of the SPT and the single template methods were compared with those of MRI-aided normalization in terms of correlation values, APEs, and concordance rates. RESULTS: The SPT (PiB negative template for the negative and equivocal groups and PiB positive template for the positive group) showed higher correlations and concordance rate and lower APEs with MRI-aided normalization than did the single template. CONCLUSIONS: Use of the SPT provides accurate normalization of amyloid images without MRI.

18 F-fluorodeoxyglucose uptake predicts pathological complete response after neoadjuvant chemotherapy for breast cancer: a retrospective cohort study.

BACKGROUND AND OBJECTIVES: (18) F-fluorodeoxyglucose ((18) F-FDG) uptake may identify poorly differentiated tumors with a high proliferation rate that are more responsive to neoadjuvant chemotherapy. METHODS: We retrospectively evaluated 273 patients (mean age, 44.2 years; range 23-78 years) newly diagnosed with stage II or III invasive ductal breast cancer between 2006 and 2010. All patients were treated with neoadjuvant chemotherapy followed by surgery. The ability of parameters to predict pathological complete response (pCR), was assessed by multivariate analysis. RESULTS: Of the 273 breast cancer patients, 30 (11.0%) achieved pCR. Univariate analysis revealed that higher histologic grade (P < 0.001), lack of estrogen receptor (ER, P < 0.001); and a higher maximal standardized uptake value (SUVmax, P < 0.001) were associated with pCR, whereas HER2/neu amplification and Ki-67 expression were not (P > 0.05 for each comparison). Multivariate analysis showed that negative ER (odds ratio [OR] = 9.98; 95% confidence interval [CI], 2.88-34.52, P < 0.001) and the SUVmax of (18) F-FDG uptake (OR per one unit increase in SUVmax = 1.09; 95% CI, 1.02-1.16, P = 0.008) were independent predictors of pCR. CONCLUSIONS: ER status and (18) F-FDG uptake are independent predictors of pCR after neoadjuvant chemotherapy for breast cancer.

Significant associations of PAI-1 genetic polymorphisms with osteonecrosis of the femoral head.

BACKGROUND: The pathogenesis of osteonecrosis of the femoral head (ONFH) has been implicated in hypofibrinolysis and blood supply interruption. Previous studies have demonstrated that decreased fibrinolytic activity due to elevated plasminogen activator inhibitor-1 (PAI-1) levels correlates with ONFH pathogenesis. The -675 4G/5G single nucleotide polymorphism (SNP rs1799889) in the PAI-1 gene promoter is associated with PAI-1 plasma level. We investigated whether rs1799889 and two other SNPs of the PAI-1 gene (rs2227631, -844 G/A in the promoter; rs11178, +10700 C/T in the 3'UTR) are associated with increased ONFH risk. METHODS: Three SNPs in PAI-1 were genotyped in 206 ONFH patients and 251 control subjects, using direct sequencing and a TaqMan® 5' allelic discrimination assay. We performed association analysis for genotyped SNPs and haplotypes with ONFH. RESULTS: The 4G allele of rs1799889, A allele of rs2227631, and C allele of rs11178 were significantly associated with increased ONFH risk (p = 0.03, p = 0.003, and p = 0.002, respectively). When we divided the population according to gender, an association between the three SNPs and increased risk of ONFH was found only in men. In another subgroup analysis based on the etiology of ONFH, rs2227631 (A allele) and rs11178 (C allele) in the idiopathic subgroup (p = 0.007 and p = 0.021) and rs1799889 (4G allele) and rs11178 (C allele) in the alcohol-induced subgroup (p = 0.042 and p = 0.015) were associated with increased risk of ONFH. In addition, a certain haplotype (A-4G-C) of PAI-1 was also significantly associated with ONFH (p < 0.001). CONCLUSION: Our findings demonstrated that three SNPs (rs1799889, rs2227631, and rs11178) of the PAI-1 gene were associated with ONFH risk. This study also suggests that PAI-1 SNPs may play an important role in ONFH.

Non-invasive prenatal detection of achondroplasia using circulating fetal DNA in maternal plasma.

PURPOSE: To perform a reliable non-invasive detection of the fetal achondroplasia using maternal plasma. METHODS: We developed a quantitative fluorescent-polymerase chain reaction (QF-PCR) method suitable for detection of the FGFR3 mutation (G1138A) causing achondroplasia. This method was applied in a non-invasive detection of the fetal achondroplasia using circulating fetal-DNA (cf-DNA) in maternal plasma. Maternal plasmas were obtained at 27 weeks of gestational age from women carrying an achondroplasia fetus or a normal fetus. RESULTS: Two percent or less achondroplasia DNA was reliably detected by QF-PCR. In a woman carrying a normal fetus, analysis of cf-DNA showed only one peak of the wild-type G allele. In a woman expected an achondroplasia fetus, analysis of cf-DNA showed the two peaks of wild-type G allele and mutant-type A allele and accurately detected the fetal achondroplasia. CONCLUSIONS: The non-invasive method using maternal plasma and QF-PCR may be useful for diagnosis of the fetal achondroplasia.

The impact of data-driven respiratory gating in clinical F-18 FDG PET/CT: comparison of free breathing and deep-expiration breath-hold CT protocol.

BACKGROUND: Respiratory motion can diminish PET image quality and lead to inaccurate lesion quantifications. Data-driven gating (DDG) was recently introduced as an effective respiratory gating technique for PET. In the current study, we investigated the clinical impact of DDG on respiratory movement in 18F-FDG PET/CT. METHOD: PET list-mode data were collected for each subject and DDG software was utilized for extracting respiratory waveforms. PET images was reconstructed using Q.clear and Q.clear + DDG, respectively. We evaluated SUVmax, SUVmean, the coefficient of variance (CoV), metabolic tumor volume (MTV), and tumor heterogeneity using the area under the curve of cumulative SUV histogram (AUC-CSH). Metabolic parameter changes were compared between each reconstruction method. The Deep-Expiration Breath Hold (DEBH) protocol was introduced for CT scans to correct spatial misalignment between PET and CT and compared with conventional free breathing. The DEBH and free breathing (FB) protocol comparison was made in a separate matching cohort using propensity core matching rather than the same patient. RESULTS: Total 147 PET/CT scans with excessive respiratory movements were used to study DDG-mediated correction. After DDG application, SUVmax (P < 0.0001; 8.15 ± 4.77 vs. 9.03 ± 5.02) and SUVmean (P < 0.0001; 4.91 ± 2.44 vs. 5.49 ± 2.68) of lung and upper abdomen lesions increased, while MTV significantly decreased (P < 0.0001; 7.07 ± 15.46 vs. 6.58 ± 15.14). In addition, the percent change of SUVs was greater in lower lung lesions compared to upper lobe lesions. Likewise, the MTV reduction was significantly greater in lower lobe lesions. No significant difference dependent on location was observed in liver lesions. DEBH-mediated CT breathing correction did not make a significant difference in lesion metabolic parameters compared to conventional free breathing. CONCLUSIONS: These results suggest that DDG correction enables more corrected quantification from respiratory movements for lesions located in the lung and upper abdomen. Therefore, we suggest that DDG is worth using as a standard protocol during 18F-FDG PET/CT imaging.

Lymphoscintigraphic Findings as Indicators of Lymphaticovenous Anastomosis Outcome in Patients With Extremity Lymphedema: A Retrospective Cohort Study.

PURPOSE: This study was performed to evaluate the usefulness of lymphoscintigraphy in predicting the surgical outcomes of lymphaticovenous anastomosis (LVA) in a patient with extremity lymphedema. PATIENTS AND METHODS: We retrospectively evaluated 133 patients with extremity lymphedema who underwent lymphoscintigraphy followed by LVA surgery from February 2018 to March 2020. Lymphoscintigraphic findings were evaluated on the following parameters: the extent of dermal backflow (small/large), lymphatic flow patterns (trunk flow pattern/proximal-restricted pattern/distal-restricted pattern), visualization of lymph nodes, and collateral lymphatic vessels. The mean circumferential difference change before and after surgery, circumferential reduction (CR) rate (%), was used as the clinical outcome variables. RESULTS: A decrease in circumference was observed in 93 (69.9%) of 133 patients after LVA. The extent of dermal backflow and lymphatic flow patterns was significantly correlated with improved clinical outcomes after LVA. The large extent of the dermal backflow group showed a more significant CR rate than the small extent (19.27% vs 1.24%, P = 0.005). The TP group showed the most significantly decreased CR rate to 21.46%, and the proximal-restricted pattern and distal-restricted pattern groups were -2.49% and -5.33%, respectively (P < 0.001). Multivariate analysis revealed that dermal backflow and lymphatic flow patterns were independent predictors of therapeutic outcome (P < 0.001). CONCLUSIONS: Our study demonstrates that pretreatment lymphoscintigraphy may help predict the therapeutic effect of LVA in patients with extremity lymphedema. Furthermore, dermal backflow and lymphatic flow patterns are independent predictors of CR rate after LVA surgery for extremity lymphedema.

Radioactive Iodine Treatment for Children and Young Adults with Thyroid Cancer in South Korea: A Population-based Study.

PURPOSE: This study investigated radioactive iodine treatment (RAIT) patterns and the secondary cancer incidence among children and young adults receiving RAIT after thyroidectomy for thyroid cancer. METHODS: This population-based cohort study used the Health Insurance Review and Assessment database of South Korea to identify a total of 18 617 children and young adults (0-29 years) who underwent thyroidectomy for thyroid cancer between 2008 and 2018. We recorded age at surgery, sex, the interval from surgery to RAIT, the doses of RAI, the number of RAIT sessions, and secondary cancer incidence. RESULTS: A total of 9548 (51.3%) children and young adults underwent 1 or more RAIT sessions. The initial dose of RAIT was 4.35 ±â€…2.19 GBq. The overall RAIT frequency fell from 60.9% to 38.5%, and the frequency of high-dose RAIT (>3.7 GBq) fell from 64.2% to 36.5% during the observational period. A total of 124 cases of secondary cancer developed during 120 474 person-years of follow-up; 43 (0.5%) in the surgery cohort and 81 (0.8%) in the RAIT cohort. Thus, the RAIT cohort was at an increased risk of secondary cancer (adjusted hazard ratio 1.52 [95% confidence interval 1.03-2.24], P = 0.035). CONCLUSION: The proportion of children and young adults receiving RAIT, and the RAI dose, fell significantly over the observational period. RAIT was associated with secondary cancers. This is of major concern in the context of child and young adult thyroid cancer survivors.

Non-Polar Myxococcus fulvus KYC4048 Metabolites Exert Anti-Proliferative Effects via Inhibition of Wnt/ß-Catenin Signaling in MCF-7 Breast Cancer Cells.

The Wnt/ß-catenin signaling pathway is involved in breast cancer and Myxococcus fulvus KYC4048 is a myxobacterial strain that can produce a variety of bioactive secondary metabolites. Although a previous study revealed that KYC4048 metabolites exhibit anti-proliferative effects on breast cancer, the biochemical mechanism involved in their effects remains unclear. In the present study, KYC4048 metabolites were separated into polar and non-polar (ethyl acetate and n-hexane) fractions via liquid-liquid extraction. The effects of these polar and non-polar KYC4048 metabolites on the viability of breast cancer cells were then determined by MTT assay. Expression levels of Wnt/ß-catenin pathway proteins were determined by Western blot analysis. Cell cycle and apoptosis were measured via fluorescence-activated cell sorting (FACS). The results revealed that non-polar KYC4048 metabolites induced cell death of breast cancer cells and decreased expression levels of WNT2B, ß-catenin, and Wnt target genes (c-Myc and cyclin D1). Moreover, the n-hexane fraction of non-polar KYC4048 metabolites was found most effective in inducing apoptosis, necrosis, and cell cycle arrest, leading us to conclude that it can induce apoptosis of breast cancer cells through the Wnt/ß-catenin pathway. These findings provide evidence that the n-hexane fraction of non-polar KYC4048 metabolites can be developed as a potential therapeutic agent for breast cancer via inhibition of the Wnt/ß-catenin pathway.

Bacterial extracellular vesicles affect endocrine therapy in MCF7 cells.

BACKGROUND: : The microbiome is important in the development and progression of breast cancer. This study investigated the effects of microbiome derived from Klebsiella on endocrine therapy of breast cancer using MCF7 cells. The bacterial extracellular vesicles (EVs) that affect endocrine therapy were established through experiments focused on tamoxifen efficacy. METHODS: : The microbiomes of breast cancer patients and healthy controls were analyzed using next-generation sequencing. Among microbiome, Klebsiella was selected as the experimental material for the effect on endocrine therapy in MCF7 cells. MCF7 cells were incubated with tamoxifen in the absence/presence of bacterial EVs derived from Klebsiella pneumoniae and analyzed by quantitative real-time polymerase chain reaction and Western blot. RESULTS: : Microbiome derived from Klebsiella is abundant in breast cancer patients especially luminal A subtype compared to healthy controls. The addition of EVs derived from K pneumoniae enhances the anti-hormonal effects of tamoxifen in MCF7 cells. The increased efficacy of tamoxifen is mediated via Cyclin E2 and p-ERK. CONCLUSION: : Based on experiments, the EVs derived from K pneumoniae are important in hormone therapy on MCF7 cells. This result provides new insight into breast cancer mechanisms and hormone therapy using Klebsiella found in the microbiome.