Publications by authors named "Sung-Won Kim"

540 Publications

Body mass index and type 2 diabetes and breast cancer survival: a Mendelian randomization study.

Am J Cancer Res 2021 15;11(8):3921-3934. Epub 2021 Aug 15.

Institute of Biomedical Sciences, Academia Sinica Taipei, Taiwan.

The causal relationship between body mass index (BMI) and type 2 diabetes (T2D) and breast cancer prognosis is still ambiguous. The aim of this study was to investigate the prognostic effect of BMI and T2D on breast cancer disease-free survival (DFS) among Asian individuals. In this two-sample Mendelian randomization (MR) study, the instrumental variables (IVs) were identified using a genome-wide association study (GWAS) among 24,000 participants in the Taiwan Biobank. Importantly, the validity of these IVs was confirmed with a previous large-scale GWAS (Biobank Japan Project, BBJ). In this study, we found that a genetic predisposition toward higher BMI (as indicated by BMI IVs, F = 86.88) was associated with poor breast cancer DFS (hazard ratio [HR] = 6.11; P < 0.001). Furthermore, higher level of genetically predicted T2D (as indicated by T2D IVs) was associated with an increased risk of recurrence of and mortality from breast cancer (HR = 1.43; P < 0.001). Sensitivity analyses, including the weighted-median approach, MR-Egger regression, Radial regression and Mendelian randomization pleiotropy residual sum and outlier (MR-PRESSO) supported the consistency of our findings. Finally, the causal relationship between BMI and poor breast cancer prognosis was confirmed in a prospective cohort study. Our MR analyses demonstrated the causal relationship between the genetic prediction of elevated BMI and a greater risk of T2D with poor breast cancer prognosis. BMI and T2D have important clinical implications and may be used as prognostic indicators of breast cancer.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8414374PMC
August 2021

Near-infrared Transillumination and Photodynamic Therapy Using Hypericin in Animal Laryngeal Tumors.

Tissue Eng Regen Med 2021 Sep 8. Epub 2021 Sep 8.

Kosin Innovative Smart Healthcare Research Center, Kosin University Gospel Hospital, Busan, 49267, Korea.

Background: We aimed to validate a pilot study of photodiagnosis using near infrared (NIR) transillumination and assess the clinical efficacy of hypericin-mediated photodynamic therapy (HYP-PDT) in a rabbit laryngeal cancer model in order to develop a novel therapeutic modality with complete remission and preservation of the functional organ.

Methods: (1) In vitro study: VX tumor cells were subcultured and subjected to HYP-PDT. (2) In vivo study: A laryngeal cancer model was developed in which 12 rabbits were inoculated with a VX tumor suspension in the submucosal area of the left vocal fold using a transoral approach. All rabbits underwent NIR transillumination using light with a wavelength of 780 nm. The survival periods of the three treatment groups (6 rabbits in Group A: HYP-PDT, 3 each in Groups B and C: laser irradiation or HYP administration only) were analyzed.

Results: The higher the HYP concentration, the lower the VX cell viability in response to HYP-PDT using 590 nm LED. Following HYP-PDT, small tumors in Group A-1 rabbits healed completely and the animals demonstrated a long survival period, and larger tumors in Group A-2 healed partially with a survival period that extended over 3 weeks after inoculation. The survival of Groups B and C were not different over the first 3 weeks of the study, and were shorter than in Group A.

Conclusion: We found HYP-PDT could be a curative therapy for early-stage cancers that may also preserve organ function, and may inhibit tumor progression and metastasis during advanced stages of laryngeal cancer.
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http://dx.doi.org/10.1007/s13770-021-00377-6DOI Listing
September 2021

Therapeutic Potential of Human Nasal Inferior Turbinate-Derived Stem Cells: Microarray Analysis of Multilineage Differentiation.

ORL J Otorhinolaryngol Relat Spec 2021 Sep 6:1-14. Epub 2021 Sep 6.

Department of Otolaryngology-Head and Neck Surgery, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea.

Introduction: Human nasal inferior turbinate-derived stem cells (hNTSCs) are attractive sources of adult stem cells for medical application because they can be easily obtained and cultivated with a highly proliferative capacity. The ability of hNTSCs to differentiate into chondrocytes, osteocytes, and neural cells makes them potential replacement therapeutic candidates in intractable disease. Nevertheless, detailed expression pattern of genes associated with trilineage differentiation (osteogenesis, chondrogenesis, and neurogenesis) in hNTSCs has not been revealed yet.

Methods: In this study, we aimed to evaluate gene expression patterns of various transcription factors and marker genes associated with a particular lineage (osteogenesis, chondrogenesis, and neurogenesis) of differentiation of hNTSCs by DNA microarrays.

Results: In microarrays, 36 transcripts such as E2F transcription factor 1, activating transcription factor 5, and AKR1B10 were upregulated and 36 transcripts such as CA9, PPFIA4, HAS2, and COL4A4 were downregulated in osteogenically differentiated hNTSCs. In chondrogenically differentiated hNTSCs, 3 transcripts (NUDT14, CPA4, and heparin-binding epidermal growth factor-like growth factor) were upregulated and 82 transcripts such as PTGS1, CLEC2D, and TET1 were downregulated. In neurally differentiated hNTSCs, 61 transcripts such as insulin-like growth factor-binding protein-1, nerve growth factor receptor, FGF1, OLFML1, and EPGN were upregulated and 98 transcripts such as ACAN, RUNX2, and C21orf96 were downregulated. In gene ontology (GO) analysis, cell signal-related GO terms were highly expressed. By contrast, catalysis GO terms and GO terms related to oxidoreductase were overrepresented in chondrogenically differentiated hNTSCs and osteogenically differentiated hNTSCs, respectively.

Conclusion: Considering overall results, hNTSCs-specific genetic information may promote further studies on intracellular mechanisms defining key features of these cells.
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http://dx.doi.org/10.1159/000516016DOI Listing
September 2021

Discovery of Highly Potent Adenosine A Receptor Agonists: Targeting Positron Emission Tomography Probes.

ACS Chem Neurosci 2021 09 1;12(18):3410-3417. Epub 2021 Sep 1.

Laboratory of Neuroimaging, National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health, Bethesda, Maryland 20892-1013, United States.

Adenosine receptor (AR) radiotracers for positron emission tomography (PET) have provided knowledge on the biodistribution of ARs in the central nervous system (CNS), which is of therapeutic interest for various neuropsychiatric disorders. Additionally, radioligands that can image changes in endogenous adenosine levels in different physiological and pathological conditions are still lacking. The binding of known antagonist adenosine A receptor (AR) radiotracer, [C]MDPX, failed to be inhibited by elevated endogenous adenosine in a rodent PET study. Since most of the known AR PET radiotracers were antagonists, we propose that an AR agonist radioligand may possess higher sensitivity to measure changes in endogenous adenosine concentration. Herein, we report our latest findings toward the development of a full agonist adenosine A radioligand for PET. Based on a 3,5-dicyanopyridine template, 16 new derivatives were designed and synthesized to optimize both binding affinity and functional activity, resulting in two full agonists (compounds and ) with single-digit nanomolar affinities and good subtype selectivity (A/A selectivity of ∼1000-fold for compound and 29-fold for compound ). Rapid O-[C]methylation provided [C] and [C] in high radiochemical yields and radiochemical purity. However, subsequent brain PET imaging in rodents showed poor brain permeability for both radioligands. An PET study using knockout mice for MDR 1a/a, BCRP, and MRP1 indicated that these compounds might be substrates for brain efflux pumps. In addition, evaluation using multiparameter optimization identified high molecular weight and high polar surface area as the main molecular descriptors responsible for low brain penetration. These results will provide further insight toward development of full agonist adenosine A radioligands and also highly potent CNS AAR drugs.
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http://dx.doi.org/10.1021/acschemneuro.1c00397DOI Listing
September 2021

Root Extract Induces the Anagen Phase in the Human Hair Follicle Dermal Papilla Cells.

Pharmaceutics 2021 Jul 27;13(8). Epub 2021 Jul 27.

School of Chemical Engineering, Sungkyunkwan University, Suwon 16419, Korea.

Restoring hair follicles by inducing the anagen phase is a promising approach to prevent hair loss. Hair follicle dermal papilla cells (HFDPCs) play a major role in hair growth via the telogen-to-anagen transition. The therapeutic effect of activates β-catenin in HFDPCs, thereby inducing the anagen phase. The HFDPCs were treated with root extract (MARE) to promote hair growth. It contains chlorogenic acid and umbelliferone and is not cytotoxic to HFDPCs at a concentration of 20%. It was demonstrated that a small amount of MARE enhances growth factor secretion (related to the telogen-to-anagen transition). Activation of β-catenin was observed in MARE-treated HFDPCs, which is crucial for inducing the anagen phase. The effect of conditioned medium derived from MARE-treated HFDPCs on keratinocytes and endothelial cells was also investigated. The findings of this study demonstrate the potency of MARE in eliciting the telogen-to-anagen transition.
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http://dx.doi.org/10.3390/pharmaceutics13081155DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8399394PMC
July 2021

Outcomes of hematopoietic cell transplantation for transformed follicular lymphoma.

Hematol Oncol 2021 Aug 25. Epub 2021 Aug 25.

Department of Hematopoietic Stem Cell Transplantation, National Cancer Center Hospital, Tokyo, Japan.

This study characterized the outcomes of patients who underwent hematopoietic cell transplantation (HCT) for transformed follicular lymphoma (tFL), and clarified the association of low-dose anti-thymocyte globulin use with outcomes after allogeneic HCT. The retrospective study cohort included 74 consecutive patients who underwent autologous (n = 23) or allogeneic (n = 51) HCT at our center from 2000 to 2017. Compared with the allogeneic HCT group, the autologous HCT group underwent fewer systemic regimens before HCT (median 2 vs. 5, p < 0.001) and were more likely to have chemosensitive disease at HCT (100% vs. 82%, p = 0.05), while age, sex and HCT-specific comorbidity index were similar between the two groups. With a median follow-up of 5.8 years among survivors, the 5-year probability of progression-free survival was 64% after autologous HCT and 55% after allogeneic HCT (p = 0.21). The 5-year cumulative incidence of non-relapse mortality was 0% after autologous HCT and 9.5% after allogeneic HCT (p = 0.062). The 5-year cumulative incidence of disease progression was similar between autologous and allogeneic HCT (36% vs. 36%, respectively, p = 0.88). In the allogeneic HCT group, the use of low-dose anti-thymocyte globulin was associated with a lower incidence of severe acute GVHD but not with an increased risk of mortality or disease progression. More than half of patients with early phase chemosensitive tFL and approximately half of those with advanced-phase tFL achieved long-term progression-free survival with autologous and allogeneic HCT, respectively. Disease progression was the major cause of treatment failure after both types of HCT. Further strategies are needed to reduce the risk of disease progression.
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http://dx.doi.org/10.1002/hon.2917DOI Listing
August 2021

Perioperative transcutaneous laryngeal ultrasonography to assess vocal cord function in thyroid surgery.

Am J Surg 2021 Aug 15. Epub 2021 Aug 15.

Department of Otolaryngology-Head and Neck Surgery, Bucheon St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, South Korea. Electronic address:

Background: Early diagnosis of vocal cord iatrogenic injury is crucial, as is perioperative vocal cord evaluation.

Methods: Vocal cord mobility detected via transcutaneous laryngeal ultrasonography was compared with that detected via laryngoscopy (the reference). The vocal cord visualization rate of ultrasonography for evaluation of mobility was explored.

Results: The diagnostic odds ratio of transcutaneous laryngeal ultrasonography was 303.2212 (95% CI, [86.7944; 1059.3198]). The area under the summary receiver operating characteristic curve was 0.944. The sensitivity, specificity, and negative predictive value were 0.9154 [0.8471; 0.9548], 0.9771 [0.9541; 0.9887], and 0.9915 [0.9868; 0.9946], respectively. The vocal cord visualization of ultrasonography used to evaluate vocal cord mobility was high (0.9572 [0.9091; 0.9804]).

Conclusions: Since transcutaneous laryngeal ultrasonography has the advantage in vocal cord visualization, it can be considered when laryngoscopy is unavailable or patients refuse laryngoscopy. Also, it is diagnostically accurate regardless of the used landmarks, VCP definition, and timing for application.
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http://dx.doi.org/10.1016/j.amjsurg.2021.08.019DOI Listing
August 2021

Considerations for the Use of Biologic Agents in Patients With Chronic Rhinosinusitis With Nasal Polyposis.

Clin Exp Otorhinolaryngol 2021 Aug 1;14(3):245-246. Epub 2021 Aug 1.

Department of Otolaryngology-Head and Neck Surgery, Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, Korea.

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http://dx.doi.org/10.21053/ceo.2021.01249DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8373833PMC
August 2021

Technical Notes on Fluoroscopy-Guided Removal of Metallic Ureteral Stents.

J Vasc Interv Radiol 2021 Aug 12. Epub 2021 Aug 12.

Department of Radiology, The Affiliated Cancer Hospital of Zhengzhou University, Zhengzhou, China.

This manuscript describes various techniques for fluoroscopy-guided removal of metallic ureteral stents. Fifteen patients underwent 17 fluoroscopy-guided removal procedures of 22 metallic ureteral stents. The simple or modified snare or retrieval hook technique was primarily used for antegrade access, whereas the loop snare technique was primarily used for retrograde access. Overall 64.7% of the stents were removed using the initial retrieval technique, and 82.4% were removed using an adjunct technique. Procedure-related complications included hematuria in 41.2% of cases and resolved spontaneously in all patients. Fluoroscopy-guided removal of metallic ureteral stents is safe and effective.
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http://dx.doi.org/10.1016/j.jvir.2021.08.001DOI Listing
August 2021

Attitudes toward Risk-Reducing Mastectomy and Risk-Reducing Salpingo-oophorectomy among Young, Unmarried, Healthy Women in Korea.

Cancer Res Treat 2021 Aug 9. Epub 2021 Aug 9.

Department of Surgery, Daerim St. Mary's Hospital, Seoul, Korea.

Purpose: This study investigated the attitudes toward risk-reducing mastectomy (RRM) and risk-reducing salpingo-oophorectomy (RRSO) as cancer prevention options for BRCA1/2 carriers in healthy, young, unmarried Korean women.

Materials And Methods: A nationally representative sample of 600 women, aged 20-39 years, completed a questionnaire on sociodemographic variables, preference for genetic testing, and intention to undergo risk-reducing surgeries after receiving information on the cancer risk of BRCA1/2 mutations and benefits of risk-reducing surgeries.

Results: A total of 54.7% and 57.7% had the intention to undergo RRM and RRSO, respectively, on the assumption that they were BRCA1/2 carriers. Older age and no intention to undergo genetic testing were associated with a reduced likelihood of undergoing RRM (odds ratio [OR], 0.30; 95% confidence interval [CI], 0.14 to 0.61 for age 35-39 years and OR, 0.35; 95% CI, 0.20 to 0.62 for no intention for genetic testing) and RRSO (OR, 0.39; 95% CI, 0.19 to 0.79 for age 35-39 years and OR, 0.30; 95% CI, 0.17 to 0.53 for no intention for genetic testing). Women who chose to be single were likely to undergo risk-reducing surgeries (OR, 1.67; 95% CI, 1.07 to 2.60 for RRM and OR, 1.56; 95% CI, 1.00 to 2.44 for RRSO).

Conclusion: More than 50% of healthy, unmarried, young Korean women were inclined to undergo prophylactic surgeries if they were BRCA1/2 mutation carriers. Further studies on decision-making process for cancer prevention in individuals at high risk for cancer need to be conducted.
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http://dx.doi.org/10.4143/crt.2021.449DOI Listing
August 2021

Prognostic Impact of Pretransplantation Quality of Life and Its Post-Transplantation Longitudinal Change after Allogeneic Hematopoietic Cell Transplantation: A Prospective Study That Administered the Short-Form Health Survey (SF-12) and EuroQol 5.

Transplant Cell Ther 2021 Aug 8. Epub 2021 Aug 8.

Department of Hematopoietic Stem Cell Transplantation, National Cancer Center Hospital, Tokyo, Japan.

In allogeneic hematopoietic cell transplantation (allo-HCT), investigator-based clinical variables have been used for pretransplantation prognostic prediction, risk adjustment, and post-transplantation long-term screenings. Although several studies have investigated the prognostic significance of pretransplantation patient-reported outcomes (PROs) and longitudinal trends in PROs after allo-HCT, few have assessed these outcomes using the Medical Outcomes Study 12-Item Short-Form Health Survey (SF-12) and EuroQol 5 Dimension (EQ-5D) index. The present study used 18 items from the SF-12 and EQ-5D index to evaluate the prognostic impact of pretransplantation quality of life (QOL) on allo-HCT outcomes and longitudinal changes in QOL in allo-HCT recipients. This single-center prospective study included consecutive patients who underwent allo-HCT at our center between October 2014 and September 2016. All participants were followed up until October 2017. The SF-12 and EQ-5D index were administered to assess patient-reported QOL before allo-HCT and at 3 months, 6 months, 1 year, and 2 years after allo-HCT when participants visited the long-term follow-up clinic. Longitudinal trends in the QOL-adjusted means were estimated using linear mixed-effects, adjusting for pretransplantation covariates and reasons for missing QOL data. Among 157 patients who underwent allo-HCT, 145 (92%) were registered in this study, and 143 with available QOL data were analyzed. The median pretransplantation scores were 45.3 for the SF-12 physical component score (PCS), 55.6 for the mental component score (MCS), 38.8 for the role/social component score (RCS), 70.0 for the visual analog scale (VAS), and 49.0 for the EQ-5D index. Overall survival (OS) was significantly improved in patients with higher pretransplantation scores on the PCS, RCS, and EQ-5D index, and multivariable analyses showed that the median pretransplantation RCS was significantly associated with OS after allo-HCT (hazard ratio, 3.66; P = .003). The longitudinal trends in the SF-12 score showed that the PCS was improved at 2 years after allo-HCT and was comparable to the normative score for the general population. The MCS remained comparable to or higher than the normative score after allo-HCT. The RCS improved significantly beginning at 6 months after allo-HCT but remained lower than the normative score at 2 years. The VAS and EQ-5D index values showed a drop at 3 months after allo-HCT. Patient-reported QOL assessed by 18 questions on the SF-12 and EQ-5D predicted prognosis, and may be used as a prognosticator to determine treatment strategies, including preparative regimens. Although we experienced a certain amount of patient attrition in the longitudinal follow-up of QOL data, we demonstrated characteristic trajectories of QOL in different domains after adjusting for background covariates and reasons for the lack of QOL data.
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http://dx.doi.org/10.1016/j.jtct.2021.07.026DOI Listing
August 2021

Effects of Lysine Cell Mass Supplementation as a Substitute for L-Lysine·HCl on Growth Performance, Diarrhea Incidence, and Blood Profiles in Weaning Pigs.

Animals (Basel) 2021 Jul 14;11(7). Epub 2021 Jul 14.

Department of Agricultural Biotechnology and Research Institute of Agriculture and Life Science, Seoul National University, Seoul 08826, Korea.

This study was conducted to evaluate the effects of lysine cell mass (LCM) as an alternative lysine source in diets for weaning pigs on growth performance, diarrhea incidence, and blood profiles. In experiment 1, a total of 200 weaning pigs, with an average body weight (BW) of 6.89 ± 1.04 kg, were allotted into one of five treatments with four replicates of 10 pigs per pen in a randomized complete block design (RCBD). The dietary treatments were composed of LCM supplementation (0, 0.25, 0.5, 0.75, or 1.0%) with partial replacement of L-lysine·HCl (0 to 0.8% for phase 1 diets and 0 to 0.07% for phase 2 diets). The BW and feed intake were recorded at the end of each phase (d 0 to 14 for phase 1, d 14 to 35 for phase 2), and diarrhea incidence was checked daily throughout the experimental period. Blood samples were taken from the jugular vein of pigs at 2 weeks and 5 weeks to determine the blood profiles of weaning pigs. In experiment 2, a total of 144 weaning pigs with an average BW of 6.44 ± 1.19 kg were allotted into one of six treatments with six replicates of four pigs per pen in RCBD. The dietary treatments were composed of LCM supplementation (0 to 3.5% for phase 1 diets and 0 to 2.2% for phase 2 diets) with replacement of L-lysine·HCl from 0 to 100%. In experiment 1, partial replacement of L-lysine·HCl with 0 to 1% LCM did not affect growth performance and diarrhea incidence of pigs. An increase in the LCM supplementation from 0 to 1% with partial replacement of L-lysine·HCl had no influence on the blood urea nitrogen concentrations, whereas it resulted in a linear decrease ( < 0.05) in the serum IgG concentrations for 5 weeks. In experiment 2, increasing the dietary level of LCM with replacement of L-lysine·HCl quadratically decreased ( < 0.05) ADG and G-F ratio for phase 2 and G-F ratio for the overall period such that 100% replacement of L-lysine·HCl with LCM decreased ADG and G-F ratio of weaning pigs. An increase in the LCM supplementation with replacement of L-lysine·HCl tended to decrease linearly ( < 0.10) the diarrhea incidence of weaning pigs for the overall period and linearly decrease ( < 0.05) the serum IgG concentrations for 2 weeks. In conclusion, partial replacement of L-lysine·HCl with LCM from 0 to 1% had no negative impacts on the growth performance, but 100% replacement of L-lysine·HCl with LCM decreased the growth performance of weaning pigs. Therefore, LCM could be included in the diets for weaning pigs up to 2.8% and 1.76% for phase 1 and phase 2, respectively, as a substitute for L-lysine·HCl without detrimental effects on the performance of weaning pigs.
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http://dx.doi.org/10.3390/ani11072092DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8300394PMC
July 2021

Near-infrared autofluorescence-based parathyroid glands identification in the thyroidectomy or parathyroidectomy: a systematic review and meta-analysis.

Langenbecks Arch Surg 2021 Jul 28. Epub 2021 Jul 28.

Department of Otolaryngology-Head and Neck Surgery, Bucheon St. Mary's Hospital, College of Medicine, The Catholic University of Korea, 327 Sosa-ro, Bucheon-si, Gyeonggi-do, 14647, Korea.

Purpose: To evaluate the diagnostic accuracy of near-infrared autofluorescence-based identification in the identification of parathyroid glands during thyroidectomy or parathyroidectomy.

Methods: The clinical studies were retrieved from PubMed, the Cochrane Central Register of Controlled Trials, Embase, Web of Science, SCOPUS, and Google Scholar. The study protocol was registered on Open Science Framework ( https://osf.io/um8rj/ ). The search period ranged from the date of each database's inception to May 2021. Cohort studies dealing with patients of whom parathyroid glands were detected by near-infrared autofluorescence and confirmed clinically or pathologically during thyroidectomy or parathyroidectomy were included. Editorials, letters, "how-I-do-it" descriptions, other site head and neck tumors, and articles with lack of diagnostic identification data were excluded. True positive, true negative, false positive, and false negative were extracted. The QUDAS ver. 2 was used to evaluate the methodological quality.

Results: Seventeen studies with 1198 participants were evaluated in this analysis. Near-infrared autofluorescence-based identification of parathyroid glands showed a diagnostic odds ratio of 228.8759 (95% confidence interval, 134.1099; 390.6063). The area under the summary receiver operating characteristic curve was 0.967. The sensitivity, specificity, negative predictive value, and positive predictive value were 0.9693 (0.9491; 0.9816), 0.9248 (0.8885; 0.9499), 0.9517 (0.8981; 0.9778), and 0.9488 (0.9167; 0.9689), respectively. Subgroup analyses were performed to compare two autofluorescence detection methods, because there was high heterogeneity in the outcomes. The diagnostic accuracy was higher in probe-based detection than in image-based detection.

Conclusions: Near-infrared autofluorescence-based identification is valuable for identifying the parathyroid glands of patients during thyroidectomy or parathyroidectomy.
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http://dx.doi.org/10.1007/s00423-021-02269-8DOI Listing
July 2021

Comparison of Narrowband Imaging and White-Light Endoscopy for Diagnosis and Screening of Nasopharyngeal Cancer.

Otolaryngol Head Neck Surg 2021 Jul 27:1945998211029617. Epub 2021 Jul 27.

Department of Otolaryngology-Head and Neck Surgery, Bucheon St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, Korea.

Objectives: We compared the diagnostic accuracies of narrowband imaging and white-light endoscopy in the detection of nasopharyngeal cancer.

Data Sources: Six databases (PubMed, Cochrane Database, Embase, Web of Science, SCOPUS, and Google Scholar).

Review Methods: The 6 databases were thoroughly reviewed by 2 authors (working independently) from their dates of inception to December 2019. Nasopharyngeal mucosal or vascular changes detected by narrowband imaging were compared to those detected by white-light endoscopy. The authors extracted true-positive, true-negative, false-positive, and false-negative parameters for each study. Methodological quality was evaluated using the Quality Assessment of Diagnostic Accuracy Studies version 2 tool. The extent of interrater agreement was assessed.

Results: Eighteen prospective or retrospective studies were included. The diagnostic odds ratio of narrowband imaging was 77.560 (95% confidence interval [CI], 37.424-160.739). The area under the summary receiver operating characteristic curve was 0.926. The sensitivity, specificity, and negative predictive value were 0.871 (95% CI, 0.808-0.915), 0.905 (95% CI, 0.816-0.953), and 0.955 (95% CI, 0.906-0.979), respectively. The correlation between sensitivity and the false-positive rate was 0.284, indicating that heterogeneity was absent. Narrowband imaging exhibited moderate interrater reliability (0.7037; 95% CI, 0.6558-0.746). Subgroup analysis showed that vascular patterns revealed by endoscopy in a screened subgroup were significantly more diagnostically accurate than mucosal patterns used for surveillance of a recurrent cancer subgroup.

Conclusions: Narrowband imaging exhibits high diagnostic accuracy and should be used in the diagnostic workup of nasopharyngeal cancer. However, further studies are necessary to confirm our results.
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http://dx.doi.org/10.1177/01945998211029617DOI Listing
July 2021

Korean Red Ginseng affects ovalbumin-induced asthma by modulating IL-12, IL-4, and IL-6 levels and the NF-κB/COX-2 and PGE pathways.

J Ginseng Res 2021 Jul 17;45(4):482-489. Epub 2020 Oct 17.

College of Veterinary Medicine, Chonnam National University, Gwangju, Republic of Korea.

Background: Asthma is an incurable hyper-responsive disease of the pulmonary system that is caused by various allergens, including indoor and outdoor stimulators. According to the Global Asthma Network, 339 million people suffered from asthma in 2018, with particularly severe forms in children. Numerous treatments for asthma are available; however, they are frequently associated with adverse effects such as growth retardation, neurological disorders (e.g., catatonia, poor concentration, and insomnia), and physiological disorders (e.g., immunosuppression, hypertension, hyperglycemia, and osteoporosis).

Methods: Korean Red Ginseng has long been used to treat numerous diseases in many countries, and we investigated the anti-asthmatic effects and mechanisms of action of Korean Red Ginseng. Eighty-four BALB/c mice were assigned to 6 treatment groups: control, ovalbumin-induced asthma group, dexamethasone treatment group, and 3 groups treated with Korean Red Ginseng water extract (KRGWE) at 5, 25, or 50 mg/kg/day for 5 days. Anti-asthmatic effects of KRGWE were assessed based on biological changes, such as white blood cell counts and differential counts in the bronchoalveolar lavage fluid, serum IgE levels, and histopathological changes in the lungs, and by examining anti-asthmatic mechanisms, such as the cytokines associated with Th1, Th2, and Treg cells and inflammation pathways.

Results: KRGWE affected ovalbumin-induced changes, such as increased white blood cell counts, increased IgE levels, and morphological changes (mucous hypersecretion, epithelial cell hyperplasia, inflammatory cell infiltration) by downregulating cytokines such as IL-12, IL-4, and IL-6 via GATA-3 inactivation and suppression of inflammation via NF-κB/COX-2 and PGE pathways.

Conclusion: KRGWE is a promising drug for asthma treatment.
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http://dx.doi.org/10.1016/j.jgr.2020.10.001DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8282494PMC
July 2021

Long-term efficacy and safety of 3D printed implant in patients with nasal septal deformities.

Eur Arch Otorhinolaryngol 2021 Jul 21. Epub 2021 Jul 21.

Department of Otolaryngology-Head and Neck Surgery, Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Banpo-daero 222, Seocho-gu, Seoul, 137-701, Republic of Korea.

Purpose: To investigate the long-term safety and efficacy of a 3D-printed bioresorbable polycaprolactone (PCL) nasal implant for nasal septal deformity reconstruction.

Methods: Fourteen patients who had undergone nasal septum reconstruction surgery using 3D-printed PCL nasal septal implants were enrolled. The primary outcome was the change in total Nasal Obstruction Symptom Evaluation (NOSE) scale scores between postoperative 3 months and current status (3.59 ± 0.51 years). The secondary outcomes were changes in the minimum cross-sectional area (MCA) and volume of both nasal cavities based on acoustic rhinometry, the cross-sectional area of the ostiomeatal unit, and the nasal septum angle of the paranasal sinus (PNS) in computed tomography (CT) images, and a visual analog scale (VAS) of the patients' subjective satisfaction.

Results: The results showed no significant changes in the MCAs (Cohen's d:0.09; p = 0.711) or nasal volume (Cohen's d:0.26; p = 0.356), the area of the ostiomeatal unit (Cohen's d:0.49; p = 0.064), septum angles (Cohen's d:0.18; p = 0.831), the NOSE scale (Cohen's d:0.14; p = 0.621), or patients' subjective satisfaction (Cohen's d:0.52; p = 0.076) during the follow-up period.

Conclusions: This homogeneous composite microporous PCL nasal septal implant demonstrated long-term clinical efficacy and safety in human tissues that required maintenance of mechanical strength. Therefore, the indications for this implant could extend to various other craniofacial reconstructions in the future.
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http://dx.doi.org/10.1007/s00405-021-06996-yDOI Listing
July 2021

A Phase I/II Multicenter Trial of HLA-Haploidentical PBSCT with PTCy for Aggressive Adult T Cell Leukemia/Lymphoma.

Transplant Cell Ther 2021 Jul 15. Epub 2021 Jul 15.

Department of Hematopoietic Stem Cell Transplantation, National Cancer Center Hospital, Tokyo, Japan. Electronic address:

Adult T cell leukemia/lymphoma (ATL) is a highly aggressive hematologic malignancy with a very poor prognosis, and most patients with ATL are elderly. Although post-transplantation cyclophosphamide (PTCy) has yielded promising results in various diseases, available data are limited regarding its outcomes in ATL. The aim of this study was to determine the safety and efficacy of reduced-intensity peripheral blood stem cell transplantation (PBSCT) from a human leukocyte antigen (HLA)-haploidentical donor using PTCy as graft-versus-host disease (GVHD) prophylaxis. This was a prospective, multicenter phase I/II study (UMIN000021783) conducted at 16 hospitals in Japan. The primary endpoint was the probability of survival with engraftment and without grade III/IV acute GVHD at day 60 after PBSCT. The expected probability of the primary endpoint was estimated to be 60%, and the threshold probability was set at 30% on the basis of previous studies. The conditioning regimen consisted of fludarabine (30 mg/m/d from day -7 to -2), melphalan (40 mg/m/d on days -3 and -2), and total body irradiation (2 Gy on day -1). GVHD prophylaxis consisted of tacrolimus starting at 0.02 mg/kg/d on day -1, PTCy (50 mg/kg/d on days +3 and +5), and mycophenolate mofetil 2000 mg/d starting on day +6. Eighteen ATL patients underwent PBSCT. The probability of patients who met the primary endpoint was 89% (95% confidence interval, 65% to 99%). The cumulative incidences of grade II to IV acute GVHD, III/IV acute GVHD, and moderate-to-severe chronic GVHD were 39%, 11%, and 17%, respectively. The probabilities of overall survival were 83% at 1 year and 73% at 2 years. The cumulative incidences of non-relapse mortality and disease progression at 1 year were 11% and 28%, respectively. HLA-haploidentical PBSCT with PTCy as GVHD prophylaxis is a valid option for patients with aggressive ATL.
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http://dx.doi.org/10.1016/j.jtct.2021.07.010DOI Listing
July 2021

Dopamine D1 and D2 receptors are distinctly associated with rest-activity rhythms and drug reward.

J Clin Invest 2021 Sep;131(18)

National Institute on Alcohol Abuse and Alcoholism, Laboratory of Neuroimaging, and.

BACKGROUNDCertain components of rest-activity rhythms such as greater eveningness (delayed phase), physical inactivity (blunted amplitude), and shift work (irregularity) are associated with increased risk for drug use. Dopaminergic (DA) signaling has been hypothesized to mediate the associations, though clinical evidence is lacking.METHODSWe examined associations between rhythm components and striatal D1 (D1R) and D2/3 receptor (D2/3R) availability in 32 healthy adults (12 female, 20 male; age 42.40 ± 12.22 years) and its relationship to drug reward. Rest-activity rhythms were assessed by 1-week actigraphy combined with self-reports. [11C]NNC112 and [11C]raclopride positron emission tomography (PET) scans were conducted to measure D1R and D2/3R availability, respectively. Additionally, self-reported drug-rewarding effects of 60 mg oral methylphenidate were assessed.RESULTSWe found that delayed rhythm was associated with higher D1R availability in caudate, which was not attributable to sleep loss or so-called social jet lag, whereas physical inactivity was associated with higher D2/3R availability in nucleus accumbens (NAc). Delayed rest-activity rhythm, higher caudate D1R, and NAc D2/3R availability were associated with greater sensitivity to the rewarding effects of methylphenidate.CONCLUSIONThese findings reveal specific components of rest-activity rhythms associated with striatal D1R, D2/3R availability, and drug-rewarding effects. Personalized interventions that target rest-activity rhythms may help prevent and treat substance use disorders.TRIAL REGISTRATIONClinicalTrials.gov: NCT03190954.FUNDINGNational Institute on Alcohol Abuse and Alcoholism (ZIAAA000550).
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http://dx.doi.org/10.1172/JCI149722DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8439593PMC
September 2021

Extended Kalman Filter-Based Power Line Interference Canceller for Electrocardiogram Signal.

Big Data 2021 Jul 14. Epub 2021 Jul 14.

Department of Information and Communication Engineering, Yeungnam University, Gyeongsan, Korea.

Cardiac diseases constitute a major root of global mortality and they are likely to persist. Electrocardiogram (ECG) is widely opted in clinics to detect countless heart illnesses. Numerous artifacts interfere with the ECG signal, and their elimination is vital to allow medical specialists to acquire valuable statistics from the ECG. The utmost artifact that is added to the ECG signal is power line interference (PLI). Numerous filtering methods have been employed in the literature to eliminate PLI from noisy ECG. This article proposes an extended Kalman filter (EKF)-based adaptive noise canceller (ANC) that comprises PLI frequency as a distinct model parameter. Thus, it is capable of tracking PLI with drifting frequency. The proposed canceller's performance is compared with state-space recursive least squares (SSRLSs) filter-based PLI canceling. The evaluation is carried out for four cases of PLI, that is, PLI with known amplitude and frequency, PLI with unknown amplitude and frequency, PLI with drifting amplitude and frequency, and PLI removal from a real-time ECG recording. The samples of the Massachusetts Institude of Technology (MIT)-Boston's Beth Israel Hospital (BIH) arrhythmia database are considered for the first three cases, whereas, for the fourth case, real ECG signal is taken from armed forces institude of cardiology, the national institude of heart diseases (AFIC/NIHD), Pakistan. Mean square error, frequency spectrum, and noise reduction are selected as performance metrics for comparison. Simulation results depict that the presented EKF-based ANC system outperforms the SSRLS-based ANC system and effectively eliminates PLI from ECG under all four investigated scenarios.
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http://dx.doi.org/10.1089/big.2021.0043DOI Listing
July 2021

Potential application of human neural crest-derived nasal turbinate stem cells for the treatment of neuropathology and impaired cognition in models of Alzheimer's disease.

Stem Cell Res Ther 2021 07 13;12(1):402. Epub 2021 Jul 13.

Department of Otolaryngology-Head and Neck Surgery, Seoul St. Mary's Hospital, The Catholic University of Korea, 222 Banpo-Daero, Seocho-gu, Seoul, 06591, Republic of Korea.

Background: Stem cell transplantation is a fascinating therapeutic approach for the treatment of many neurodegenerative disorders; however, clinical trials using stem cells have not been as effective as expected based on preclinical studies. The aim of this study is to validate the hypothesis that human neural crest-derived nasal turbinate stem cells (hNTSCs) are a clinically promising therapeutic source of adult stem cells for the treatment of Alzheimer's disease (AD).

Methods: hNTSCs were evaluated in comparison with human bone marrow-derived mesenchymal stem cells (hBM-MSCs) according to the effect of transplantation on AD pathology, including PET/CT neuroimaging, immune status indicated by microglial numbers and autophagic capacity, neuronal survival, and cognition, in a 5 × FAD transgenic mouse model of AD.

Results: We demonstrated that hNTSCs showed a high proliferative capacity and great neurogenic properties in vitro. Compared with hBM-MSC transplantation, hNTSC transplantation markedly reduced Aβ42 levels and plaque formation in the brains of the 5 × FAD transgenic AD mice on neuroimaging, concomitant with increased survival of hippocampal and cortex neurons. Moreover, hNTSCs strongly modulated immune status by reducing the number of microglia and the expression of the inflammatory cytokine IL-6 and upregulating autophagic capacity at 7 weeks after transplantation in AD models. Notably, compared with transplantation of hBM-MSCs, transplantation of hNTSCs significantly enhanced performance on the Morris water maze, with an increased level of TIMP2, which is necessary for spatial memory in young mice and neurons; this difference could be explained by the high engraftment of hNTSCs after transplantation.

Conclusion: The reliable evidence provided by these findings reveals a promising therapeutic effect of hNTSCs and indicates a step forward the clinical application of hNTSCs in patients with AD.
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http://dx.doi.org/10.1186/s13287-021-02489-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8278635PMC
July 2021

Intraoperative Neural Monitoring for Early Vocal Cord Function Assessment After Thyroid Surgery: A Systematic Review and Meta-Analysis.

World J Surg 2021 Jun 30. Epub 2021 Jun 30.

Department of Otolaryngology-Head and Neck Surgery, Bucheon St. Mary's Hospital, College of Medicine, The Catholic University of Korea, 327 Sosa-ro, Bucheon-si, Gyeonggi-do, 14647, Korea.

Objective This study evaluated the diagnostic accuracies of various forms of intraoperative neural monitoring (IONM) in terms of predicting vocal cord palsy after thyroidectomy. Methods Two authors independently reviewed the six databases (PubMed, the Cochrane database, Embase, the Web of Science, SCOPUS, and Google Scholar) from their dates of inception to March 2021. Intraoperative electromyographic neuromonitoring (IONM) was compared with laryngoscopic detection (the reference method). True-positive, true-negative, false-positive, and false-negative data were extracted from each study. Methodological quality was evaluated using the Quality Assessment of Diagnostic Accuracy Studies ver. 2 tool. Results Twenty-seven prospective or retrospective studies were included. The diagnostic odds ratio for IONM was 152.9623 ([95% confidence interval [75.4249; 310.2085]. The area under the summary receiver operating characteristic curve was 0.966. The sensitivity, specificity, negative predictive value, and positive predictive value were 0.8219 ([0.6862; 0.9069]), 0.9783 ([0.9659; 0.9863]), 0.9943 ([0.9880; 0.9973]), and 0.5523 ([0.4458; 0.6542]), respectively. The correlation between sensitivity and false-positive rate was 0.200, indicating the absence of heterogeneity. Subgroup analysis showed that the diagnostic accuracies of the continuous IONM was higher than those of intermittent IONM, and recent publications (> 2011) was higher than early publication (< 2010). Conclusions As the technology and knowledge of IONM have been accumulated and progressed over the past decades, the predictive value of IONM in postoperative vocal cord palsy has also improved. Moreover, the advances of continuous IONM technology could make a breakthrough in vocal cord evaluation after thyroid surgery.
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http://dx.doi.org/10.1007/s00268-021-06225-xDOI Listing
June 2021

Anatomical Variations Associated With Maxillary Sinus Fungal Ball.

Ear Nose Throat J 2021 Jun 28:1455613211028470. Epub 2021 Jun 28.

Department of Otolaryngology-Head and Neck Surgery, Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea.

Objective: We investigated the anatomical and dental factors associated with unilateral maxillary sinus fungal ball (MSFB). Also, we evaluated the effect of combinations of those factors on the incidence of MSFB.

Methods: Three hundred patients were divided into MSFB, normal, and chronic rhinosinusitis (CRS) groups. We reviewed paranasal computed tomography scans for the presence of deviated nasal septum, concha bullosa (CB), Haller cells, and various dental factors. Also, we measured the ethmoid infundibulum, maxillary natural ostium, and CB.

Results: Maxillary sinus fungal ball showed a more significant association with CB compared to the other 2 groups (37%, < .05). The MSFB group had a lower rate of Haller cells than the normal group (10% vs 22%, respectively; < .05). Also, the MSFB group had a wider maxillary sinus ostium than the normal group (7.07 ± 1.8 vs 5.48 ± 1.3 mm; < .01). Moreover, the combination of CB and Haller cells was significantly associated with a decreased rate of the fungal ball ( = .047, odds ratio = 0.694). The dental factors were more prevalent in the MSFB and CRS groups (73% and 75%, respectively) than in the normal group (32%, < .001).

Conclusions: Maxillary sinus fungal ball is significantly associated with CB, Haller cells, an increased maxillary sinus ostium size, and dental factors.
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http://dx.doi.org/10.1177/01455613211028470DOI Listing
June 2021

A Magnetically Powered Stem Cell-Based Microrobot for Minimally Invasive Stem Cell Delivery via the Intranasal Pathway in a Mouse Brain.

Adv Healthc Mater 2021 Jun 23:e2100801. Epub 2021 Jun 23.

Department of Robotics Engineering, DGIST-ETH Microrobotics Research Center, Daegu Gyeongbuk Institute of Science and Technology (DGIST), Daegu, 42988, Republic of Korea.

Targeted stem cell delivery with microrobots has emerged as a potential alternative therapeutic strategy in regenerative medicine, and intranasal administration is an effective approach for minimally invasive delivery of therapeutic agents into the brain. In this study, a magnetically powered stem cell-based microrobot ("Cellbot") is used for minimally invasive targeted stem cell delivery to the brain through the intranasal passage. The Cellbot is developed by internalizing superparamagnetic iron oxide nanoparticles (SPIONs) into human nasal turbinate stem cells. The SPIONs have no influence on hNTSC characteristics, including morphology, cell viability, and neuronal differentiation. The Cellbots are capable of proliferation and differentiation into neurons, neural precursor cells, and neurogliocytes. The Cellbots in the microfluidic channel can be reliably manipulated by an external magnetic field for orientation and position control. Using an ex vivo model based on brain organoids, it is determined that the Cellbots can be transplanted into brain tissue. Using a murine model, it is demonstrated that the Cellbots can be intranasally administered and magnetically guided to the target tissue in vivo. This approach has the potential to effectively treat central nervous system disorders in a minimally invasive manner.
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http://dx.doi.org/10.1002/adhm.202100801DOI Listing
June 2021

Functional annotation of the 2q35 breast cancer risk locus implicates a structural variant in influencing activity of a long-range enhancer element.

Am J Hum Genet 2021 07 18;108(7):1190-1203. Epub 2021 Jun 18.

Genomic Epidemiology Group, German Cancer Research Center (DKFZ), Heidelberg 69120, Germany.

A combination of genetic and functional approaches has identified three independent breast cancer risk loci at 2q35. A recent fine-scale mapping analysis to refine these associations resulted in 1 (signal 1), 5 (signal 2), and 42 (signal 3) credible causal variants at these loci. We used publicly available in silico DNase I and ChIP-seq data with in vitro reporter gene and CRISPR assays to annotate signals 2 and 3. We identified putative regulatory elements that enhanced cell-type-specific transcription from the IGFBP5 promoter at both signals (30- to 40-fold increased expression by the putative regulatory element at signal 2, 2- to 3-fold by the putative regulatory element at signal 3). We further identified one of the five credible causal variants at signal 2, a 1.4 kb deletion (esv3594306), as the likely causal variant; the deletion allele of this variant was associated with an average additional increase in IGFBP5 expression of 1.3-fold (MCF-7) and 2.2-fold (T-47D). We propose a model in which the deletion allele of esv3594306 juxtaposes two transcription factor binding regions (annotated by estrogen receptor alpha ChIP-seq peaks) to generate a single extended regulatory element. This regulatory element increases cell-type-specific expression of the tumor suppressor gene IGFBP5 and, thereby, reduces risk of estrogen receptor-positive breast cancer (odds ratio = 0.77, 95% CI 0.74-0.81, p = 3.1 × 10).
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http://dx.doi.org/10.1016/j.ajhg.2021.05.013DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8322933PMC
July 2021

Delivery of a spheroids-incorporated human dermal fibroblast sheet increases angiogenesis and M2 polarization for wound healing.

Biomaterials 2021 08 7;275:120954. Epub 2021 Jun 7.

School of Chemical Engineering, Sungkyunkwan University, Suwon, Gyeonggi, 16419, Republic of Korea. Electronic address:

Low cell engraftment is a major problem in tissue engineering. Although various methods related with cell sheets have been attempted to resolve the issue, low cell viability due to oxygen and nutrient depletion remains an obstacle toward advanced therapeutic applications. Cell therapy using fibroblasts is thought of as a good alternative due to the short doubling times of fibroblasts together with their immunomodulatory properties. Furthermore, three-dimensional (3D) fibroblasts exhibit unique angiogenic and inflammation-manipulating properties that are not present in two-dimensional (2D) forms. However, the therapeutic effect of 3D fibroblasts in tissue regeneration has not been fully elucidated. Macrophage polarization has been widely studied, as it stimulates the transition from the inflammation to the proliferation phase of wound healing. Although numerous strategies have been developed to achieve better polarization of macrophages, the low efficacy of these strategies and safety issues remain problematic. To this end, we introduced a biocompatible flat patch with specifically designed holes that form a spheroids-incorporated human dermal fibroblast sheet (SIS) to mediate the activity of inflammatory cytokines for M2 polarization and increase angiogenic efficacy. We further confirmed in vivo enhancement of wound healing with an SIS-laden skin patch (SISS) compared to conventional cell therapy.
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http://dx.doi.org/10.1016/j.biomaterials.2021.120954DOI Listing
August 2021

Predictive value of ipsilateral central lymph node metastasis for contralateral central lymph node metastasis in patients with thyroid cancer: Systematic review and meta-analysis.

Head Neck 2021 Oct 14;43(10):3177-3184. Epub 2021 Jun 14.

Department of Otolaryngology - Head and Neck Surgery, Bucheon St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, South Korea.

Careful consideration of prophylactic central compartment dissection is required to ensure that its benefits outweigh its risks in the thyroid cancer. Sixteen prospective or retrospective studies were included. True positive, true negative, false positive, and false negative were extracted from each study. The diagnostic odds ratio of ipsilateral central lymph node metastasis (iCLNM) for predicting contralateral central lymph node metastasis (cCLNM) was 12.9237 (95% confidence interval [CI], 8.1595-20.4695). The area under the summary receiver operating characteristic curve was 0.854. The sensitivity, specificity, and negative predictive value were 0.8925 [0.8232-0.9368], 0.6884 [0.6311-0.7404], and 0.9802 [0.9631-0.9894], respectively. There were strong correlations between cCLNM and clinicopathologic characteristics. Ipsilateral central lymph node pathology is useful for predicting contralateral central compartment invasion in patients with thyroid cancer. In addition, clinicopathologic characteristics were associated with cCLNM in patients with unilateral thyroid cancer.
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http://dx.doi.org/10.1002/hed.26787DOI Listing
October 2021

Using a Tailored Digital Health Intervention for Family Communication and Cascade Genetic Testing in Swiss and Korean Families With Hereditary Breast and Ovarian Cancer: Protocol for the DIALOGUE Study.

JMIR Res Protoc 2021 Jun 11;10(6):e26264. Epub 2021 Jun 11.

Department of Clinical Research, University of Basel, Basel, Switzerland.

Background: In hereditary breast and ovarian cancer (HBOC), family communication of genetic test results is essential for cascade genetic screening, that is, identifying and testing blood relatives of known mutation carriers to determine whether they also carry the pathogenic variant, and to propose preventive and clinical management options. However, up to 50% of blood relatives are unaware of relevant genetic information, suggesting that potential benefits of genetic testing are not communicated effectively within family networks. Technology can facilitate communication and genetic education within HBOC families.

Objective: The aims of this study are to develop the K-CASCADE (Korean-Cancer Predisposition Cascade Genetic Testing) cohort in Korea by expanding an infrastructure developed by the CASCADE (Cancer Predisposition Cascade Genetic Testing) Consortium in Switzerland; develop a digital health intervention to support the communication of cancer predisposition for Swiss and Korean HBOC families, based on linguistic and cultural adaptation of the Family Gene Toolkit; evaluate its efficacy on primary (family communication of genetic results and cascade testing) and secondary (psychological distress, genetic literacy, active coping, and decision making) outcomes; and explore its translatability using the reach, effectiveness, adoption, implementation, and maintenance framework.

Methods: The digital health intervention will be available in French, German, Italian, Korean, and English and can be accessed via the web, mobile phone, or tablet (ie, device-agnostic). K-CASCADE cohort of Korean HBOC mutation carriers and relatives will be based on the CASCADE infrastructure. Narrative data collected through individual interviews or mini focus groups from 20 to 24 HBOC family members per linguistic region and 6-10 health care providers involved in genetic services will identify the local cultures and context, and inform the content of the tailored messages. The efficacy of the digital health intervention against a comparison website will be assessed in a randomized trial with 104 HBOC mutation carriers (52 in each study arm). The translatability of the digital health intervention will be assessed using survey data collected from HBOC families and health care providers.

Results: Funding was received in October 2019. It is projected that data collection will be completed by January 2023 and results will be published in fall 2023.

Conclusions: This study addresses the continuum of translational research, from developing an international research infrastructure and adapting an existing digital health intervention to testing its efficacy in a randomized controlled trial and exploring its translatability using an established framework. Adapting existing interventions, rather than developing new ones, takes advantage of previous valid experiences without duplicating efforts. Culturally sensitive web-based interventions that enhance family communication and understanding of genetic cancer risk are timely. This collaboration creates a research infrastructure between Switzerland and Korea that can be scaled up to cover other hereditary cancer syndromes.

Trial Registration: ClinicalTrials.gov NCT04214210; https://clinicaltrials.gov/ct2/show/NCT04214210 and CRiS KCT0005643; https://cris.nih.go.kr/cris/.

International Registered Report Identifier (irrid): PRR1-10.2196/26264.
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http://dx.doi.org/10.2196/26264DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8235289PMC
June 2021

BRCA and Breast Cancer-Related High-Penetrance Genes.

Adv Exp Med Biol 2021 ;1187:473-490

Daerim St.Mary's Hospital, Seoul, South Korea.

Genetic susceptibility explains 5-10% of all breast cancer cases. High-penetrance breast cancer susceptibility genes deliberate a greater than tenfold relative risk of breast cancer. BRCA1 and BRCA2 genes are the most common cause of hereditary breast cancer, and TP53, PTEN, and SKT11 (LKB1) are rarely present. The prevalence of BRCA1 and BRCA2 genetic alterations differ in various ethnic groups. The Korean Hereditary Breast Cancer (KOHBRA) Study, nationwide-scale study, was established to acquire evidence for the accurate risk assessment and management of hereditary breast and ovarian cancer (HBOC) in Korea prospectively since 2007. In this chapter, we review previous research related to hereditary breast cancer and summarize the present concepts and research results centered on the Korean Hereditary Breast Cancer Research at this time.
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http://dx.doi.org/10.1007/978-981-32-9620-6_25DOI Listing
May 2021

A shared frailty model for multivariate longitudinal data on adverse event of radiation therapy.

Biom J 2021 May 5. Epub 2021 May 5.

School of Mathematics, University of Edinburgh, James Clark Maxwell Building, The King's Buildings, Edinburgh, UK.

Oral mucositis is an inflammatory adverse event when treating head and neck cancer patients with radiation therapy (RT). The severity of its occurrence is believed to mainly depend on its site and the distribution of a cumulative radiation dose in the mouth area. The motivating study investigating differences in radiosensitivities (mucositis progression) at distinct sites where the severity of mucositis is assessed regularly at eight distinct sites on an ordinal scale results in multivariate longitudinal data and thus poses certain challenges. To deal with the multivariate longitudinal data in this particular setting, we take a time-to-event approach focusing on the first occurrence of severe mucositis at the distinct sites using the fact that the site-specific cumulative radiation dose thought to be the main driver of oral mucositis develops over time. Thereby, we may address multivariate longitudinal processes in a simpler and more compact fashion. In this article, to find out differences in mucositis progression at eight distinct sites we propose a shared frailty model for multivariate parallel processes within individuals. The shared frailty model directly incorporating 'process indicators' as covariates turns out to adequately explain the differences in the parallel processes (here, mucositis progressions at distinct sites) while taking individual effects into account. The parallel result with the one from the previous analysis based on the same data but conducted with an alternative statistical methodology shows adequacy of the proposed approach.
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http://dx.doi.org/10.1002/bimj.202000237DOI Listing
May 2021

Usefulness of hematopoietic progenitor cell monitoring to predict autologous peripheral blood stem cell harvest timing: A single-center retrospective study.

Transfus Apher Sci 2021 Aug 24;60(4):103150. Epub 2021 Apr 24.

Department of Hematopoietic Stem Cell Transplantation, National Cancer Center Hospital, Japan.

Introduction: In autologous peripheral blood stem cell harvest (APBSCH), CD34-positive cells have been measured to assess the numbers of hematopoietic stem cells, but measurement requires specialized equipment. Recently, there was a report that peripheral blood hematopoietic progenitor cells (HPCs) are useful indicators of the presence of hematopoietic stem cells. We examined the usefulness of HPC monitoring to predict APBSCH timing.

Methods: We retrospectively analyzed the relationship between HPC and collected CD34-positive cells in 84 consecutive patients who underwent APBSCH.

Results: According to the receiver operating characteristics curve for the collection of ≥2 × 106 CD34-positive cells/kg, the HPC cut-off value on the day before collection was 21/μL, while that on the day of collection was 41/μL. No significant factors were found in the univariate analysis except for the HPC count on the day before collection (p < 0.001) and the day of collection (p < 0.001). According to the multivariate analysis, the HPC count on the day before collection (p < 0.001) and the day of collection (p < 0.001) were also factors that strongly influenced the quantity of CD34-positive cells collected.

Conclusion: Our results suggest that the HPC count on not only the day of collection but also the day before collection is a good indicator for appropriate APBSCH timing.
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http://dx.doi.org/10.1016/j.transci.2021.103150DOI Listing
August 2021
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