Thyroid nodules represent a prevalent condition that is detectable via palpation or ultrasound. In recent years, there has been a paradigm shift toward enhanced diagnostic precision and less aggressive therapeutic approaches, highlighting the growing necessity for tailored clinical recommendations to optimize patient outcomes. The Korean Thyroid Association (KTA) has developed guidelines for managing patients with thyroid nodules, following a comprehensive review by task force members of the relevant literature identified via electronic database searches. The recommendations are provided with a level of recommendation for each section. The guidelines encompass thyroid cancer screening in high-risk groups, appropriate diagnostic methods for thyroid nodules, role of pathologic and molecular marker testing in making a diagnosis, long-term follow-up and treatment of benign thyroid nodules, and special considerations for pregnant women. The major revisions that were made in the 2023 guidelines were the definition of high-risk groups for thyroid cancer screening, application of the revised Korean Thyroid Imaging Reporting and Data System (K-TIRADS), addition of the role of core needle biopsy and molecular marker tests, application of active surveillance in patients with low-risk papillary thyroid microcarcinoma, and updated indications for nonsurgical treatment of benign thyroid nodules. In the 2024 revision of the KTA guidelines for thyroid cancer, the evidence for some recommendations has been updated to address the tumor size in the context of active surveillance in patients with low-risk thyroid cancer and the surgical size cutoff. These evidence-based recommendations serve to inform clinical decision-making in the management of thyroid nodules, thereby facilitating the delivery of optimal and efficacious treatments to patients.

Bile pigment, bilirubin, and biliverdin concentrations may change as a results of biliary tract cancer (BTC) altering the mechanisms of radical oxidation and heme breakdown. We explored whether changes in bile pigment components could help distinguish BTC from benign biliary illness by evaluating alterations in patients with BTC. We collected bile fluid from 15 patients with a common bile duct stone (CBD group) and 63 individuals with BTC (BTC group). We examined the bile fluid’s bilirubin, biliverdin reductase (BVR), heme oxygenase (HO-1), and bacterial taxonomic abundance. Serum bilirubin levels had no impact on the amounts of bile HO-1, BVR, or bilirubin. In comparison to the control group, the BTC group had considerably higher amounts of HO-1, BVR, and bilirubin in the bile. The areas under the curve for the receiver operating characteristic curve analyses of the BVR and HO-1 were 0.832 (p<0.001) and 0.891 (p<0.001), respectively. Firmicutes was the most prevalent phylum in both CBD and BTC, according to a taxonomic abundance analysis, however the Firmicutes/Bacteroidetes ratio was substantially greater in the BTC group than in the CBD group. The findings of this study showed that, regardless of the existence of obstructive jaundice, biliary carcinogenesis impacts heme degradation and bile pigmentation, and that the bile pigment components HO-1, BVR, and bilirubin in bile fluid have a diagnostic significance in BTC. In tissue biopsies for the diagnosis of BTC, particularly for distinguishing BTC from benign biliary strictures, bile pigment components can be used as additional biomarkers.

Purpose: This study aimed to investigate the oncologic outcomes and prognostic factors of salvage treatments in patients with recurrent oropharyngeal squamous cell carcinoma (OPSCC) after radiotherapy (RT)-based treatment. Materials and Methods: A cancer registry was used to retrieve the records of 337 patients treated with definitive RT or concurrent chemoradiotherapy (CRT) from 2008 to 2018 at a single institution. The poor-responder group (PRG) was defined as patients with residual or recurrent disease after primary treatment, and the oncologic outcomes for each salvage treatment method were analyzed. In addition, prognostic indicators of recurrence-free survival (RFS) and overall survival (OS) were identified in patients who underwent salvage treatment. Results: After initial (C)RT, the PRG comprised 71 of the 337 patients (21.1%): 18 patients had residual disease, and 53 had recurrence after primary treatment (mean time to recurrence 19.5 months). Of these, 63 patients received salvage treatment (surgery 57.2%, re-(C)RT 23.8%, and chemotherapy 19.0%), and the salvage success rate was 47.6% at the last follow-up. The overall 2-year OS for salvage treatments was 56.4% (60.8% for the salvage surgery group and 46.2% for the salvage re-(C)RT). Salvage surgery patients with negative resection margins had better oncologic outcomes than those with close/positive resection margins. Using multivariate analyses, locoregional recurrence and residual disease after primary surgery were associated with poor outcome after salvage treatment. In Kaplan-Meier analyses, p16 status was significantly associated with OS in the initial treatment setting but not in the salvage setting. Conclusion In recurrent OPSCC after RT-based treatment, successful salvage was achieved in 56.4% patients who had undergone salvage surgery and radiation treatment. Salvage treatment methods should be selected carefully, given recurrence site as a prognostic factor for RFS.

Thyroid nodules are a prevalent condition that can be detected through palpation or ultrasound. However, a small fraction of these nodules can be cancerous, and even benign nodules can cause symptoms if they grow and compress surrounding tissue. As such, it is important to monitor thyroid nodules and determine appropriate treatment options. In recent years, there has been a shift towards enhancing diagnostic accuracy and less aggressive treatment options. As a result, there is a growing need for the development of appropriate recommendations for their clinical application to ensure optimal patient outcomes. The present clinical practice guideline was developed by extracting the nodule section from the prior version of guidelines and updating it to fit the Korean circumstances. Task force members reviewed relevant studies selected after electronic database searching, and the recommendations are provided with a level of recommendation for each section. The revised guideline includes recommendations for thyroid cancer screening in high-risk groups, appropriate diagnostic methods for thyroid nodules, the role of pathological and molecular marker tests in diagnosis, long-term follow-up and treatment of benign thyroid nodules, and special considerations for pregnant women. The major changes in this revision are the definition of high-risk groups for thyroid cancer screening, the application of the revised Korean Thyroid Imaging Reporting and Data System (K-TIRADS), the addition of the role of core needle biopsy and molecular marker tests, the application of active surveillance in low-risk papillary thyroid microcarcinoma, and updated indications for non-surgical treatment of benign thyroid nodules. These evidence-based recommendations are expected to assist in clinical decision-making for thyroid nodule management, ensuring that patients receive the most appropriate and effective treatment options.

Purpose: In this pilot study, using next-generation sequencing and integrated messenger RNA (mRNA) sequencing, we investigated circulating microRNA (miRNA) expression profiling from bile-derived exosomes to identify dysregulated miRNA signatures and oncogenic pathways and determine their effects on targeted mRNAs in cholangiocarcinoma (CCA).Moreover, we explored the possibility that genetic analysis using bile-derived exosomes may replace gene analysis using tissue. Methods: Bile was collected from a patient with perihilar CCA before curative resection. As a control, bile was collected from a patient with a common bile duct stone. Exosomes were isolated from the bile, and we performed next-generation miRNA sequencing using isolated exosomes. To evaluate miRNA-mRNA interactions, mRNA sequencing was performed using bile fluid in both patients. Results: We identified 22 differentially expressed miRNAs. More than 65% of the predicted mRNA targets of those miRNAs were actually differentially expressed between control and CCA bile samples. In functional pathway analysis, targets of 22 miRNAs were primarily enriched in mitogen-activated protein kinase, platelet derived growth factor, vascular endothelial growth factor, epidermal growth factor receptor, and p53 signaling. In particular, in the functional assessment of miRNAmRNA interactions, RAS pathways, including downstream pathways (PI3K-AKT-mTOR and RAS-RAF-MEK-ERK), were determined to be enriched. Conclusion Circulating miRNAs in bile-derived exosomes provide new information for the development of miRNA analysis in CCA. These miRNAs may represent the oncogenic characteristics of CCA tissue, enabling them to be used instead of tissue samples for the diagnosis of CCA. Further research investigating circulating miRNAs in bile exosomes may lead to more rational, targeted approaches to treatment.

Purpose: In this pilot study, using next-generation sequencing and integrated messenger RNA (mRNA) sequencing, we investigated circulating microRNA (miRNA) expression profiling from bile-derived exosomes to identify dysregulated miRNA signatures and oncogenic pathways and determine their effects on targeted mRNAs in cholangiocarcinoma (CCA).Moreover, we explored the possibility that genetic analysis using bile-derived exosomes may replace gene analysis using tissue. Methods: Bile was collected from a patient with perihilar CCA before curative resection. As a control, bile was collected from a patient with a common bile duct stone. Exosomes were isolated from the bile, and we performed next-generation miRNA sequencing using isolated exosomes. To evaluate miRNA-mRNA interactions, mRNA sequencing was performed using bile fluid in both patients. Results: We identified 22 differentially expressed miRNAs. More than 65% of the predicted mRNA targets of those miRNAs were actually differentially expressed between control and CCA bile samples. In functional pathway analysis, targets of 22 miRNAs were primarily enriched in mitogen-activated protein kinase, platelet derived growth factor, vascular endothelial growth factor, epidermal growth factor receptor, and p53 signaling. In particular, in the functional assessment of miRNAmRNA interactions, RAS pathways, including downstream pathways (PI3K-AKT-mTOR and RAS-RAF-MEK-ERK), were determined to be enriched. Conclusion Circulating miRNAs in bile-derived exosomes provide new information for the development of miRNA analysis in CCA. These miRNAs may represent the oncogenic characteristics of CCA tissue, enabling them to be used instead of tissue samples for the diagnosis of CCA. Further research investigating circulating miRNAs in bile exosomes may lead to more rational, targeted approaches to treatment.

Asthma is a heterogeneous disease whose development is shaped by a variety of environmental and genetic factors. While several recent studies suggest that microbial dysbiosis in the gut may promote asthma, little is known about the relationship between the recently discovered lung microbiome and asthma. Innate lymphoid cells (ILCs) have also been shown recently to participate in asthma. To investigate the relationship between the lung microbiome, ILCs, and asthma, we recruited 23 healthy controls (HC), 42 patients with non-severe asthma, and 32 patients with severe asthma. Flow cytometry analysis showed severe asthma associated with fewer natural cytotoxicity receptor (NCR) + ILC3s in the lung.Similar changes in other ILC subsets, macrophages, and monocytes were not observed. The asthma patients did not differ from the HC in terms of the alpha and beta-diversity of the lung and gut microbiomes. However, lung function correlated positively with both NCR + ILC3 frequencies and microbial diversity in the lung. Sputum NCR + ILC3 frequencies correlated positively with lung microbiome diversity in the HC, but this relationship was inversed in severe asthma. Together, these data suggest that airway NCR + ILC3s may contribute to a healthy commensal diversity and normal lung function.

Background: As an instrument for measuring body composition in experimental animals, dual energy X-ray absorptiometry (DXA) is ideal for accuracy, cost, and measurement efficiency. However, there is too little insight into the effectiveness of the various aspects of applying DXA to experimental animals. We investigated whether to compare and verify the precision and accuracy of DXA and nuclear magnetic resonance (NMR) animal body composition analyzers. Methods: We used 30 Institution of Cancer Research mice in the study. First, in order to evaluate the reproducibility of DXA and NMR, we did repeated measurements by repositioning each mouse in anesthesia and euthanasia states. Subsequently, the accuracy of each device was evaluated by comparing the weight measured before the experiment, the weight of the tissue extracted from the mice after the experiment, and the measured DXA and NMR. In addition, when measuring the body composition of animals, we compared the time and the measurable body composition parameters and summarized the advantages and disadvantages of the 2 devices. Results: Compared to NMR, DXA had the advantage of a fast measurement of bone composition and rapid image analysis. In addition, DXA showed a higher correlation (>95%) with fat mass, lean mass baseline than did NMR (>85%). Conclusions In conclusion, DXA was confirmed to have higher precision and measurement accuracy than did NMR. Therefore, DXA is an effective method for evaluating the body composition of experimental animals.

Vascular endothelial growth factor (VEGF) plays a pivotal role in pathologic ocular neovascularization and vascular leakage via activation of VEGF receptor 2 (VEGFR2). This study was undertaken to evaluate the therapeutic mechanisms and effects of the tetrapeptide Arg-Leu-Tyr-Glu (RLYE), a VEGFR2 inhibitor, in the development of vascular permeability and choroidal neovascularization (CNV). In cultured human retinal microvascular endothelial cells (HRMECs), treatment with RLYE blocked VEGF-A-induced phosphorylation of VEGFR2, Akt, ERK, and endothelial nitric oxide synthase (eNOS), leading to suppression of VEGF-A-mediated hyper-production of NO. Treatment with RLYE also inhibited VEGF-A-stimulated angiogenic processes (migration, proliferation, and tube formation) and the hyperpermeability of HRMECs, in addition to attenuating VEGF-A-induced angiogenesis and vascular permeability in mice. The anti-vascular permeability activity of RLYE was correlated with enhanced stability and positioning of the junction proteins VE-cadherin, β-catenin, claudin-5, and ZO-1, critical components of the cortical actin ring structure and retinal endothelial barrier, at the boundary between HRMECs stimulated with VEGF-A. Furthermore, intravitreally injected RLYE bound to retinal microvascular endothelium and inhibited laser-induced CNV in mice. These findings suggest that RLYE has potential as a therapeutic drug for the treatment of CNV by preventing VEGFR2-mediated vascular leakage and angiogenesis.
Actins ; Animals ; Capillary Permeability ; Choroid ; Choroidal Neovascularization ; Claudin-5 ; Endothelial Cells ; Endothelium ; Humans ; Macular Degeneration ; Mice ; Nitric Oxide Synthase Type III ; Permeability ; Phosphorylation ; Receptors, Vascular Endothelial Growth Factor ; Retinaldehyde ; Vascular Endothelial Growth Factor A

This study was conducted to analyze the strengths and weaknesses of a 3-week family medicine clerkship program based on the results of an online survey taken by the students (N=127) and a structured interview with a focus group (n=10), aimed to improve the quality of the clerkship program. The online survey contained questions pertaining to goals, schedule, contents, arrangement, atmosphere, environment, evaluation, and satisfaction regarding the clerkship. The focus group interview addressed the schedule and achievements of the program. Scores were reported on a 5-point Likert scale. Most students were highly satisfied with the overall quality of the clerkship. The structured interview results showed that 97.6% of the clerkship program was executed according to the schedule. The focus group reported a perfect score of 5 points on several measures including: accomplishment of the educational goals of the family medicine clerkship, providing many chances to obtain medical histories and perform physical examinations on real patients, experience with various symptoms and diseases, positive attitudes of faculty members when teaching, notification of the guidelines for evaluation beforehand, well-constructed and effective clerkship schedule, and reflection of student feedback. However, the focus group gave low scores on: support for health accidents of students, access to patient information, enough opportunities to practice clinical skills, appropriate rest facilities for students, and fairness of clerkship evaluation process. In conclusion, the structured evaluation performed after the 3-week clerkship program motivated students and helped them ensure an efficient clerkship. This structured evaluation also suggested basic data to make the professor who is subject of the assessment. This study shows that structured assessment is an effective method which can be used to improve the quality of clerkships.
Appointments and Schedules ; Atmosphere ; Clinical Clerkship ; Clinical Competence ; Family Practice ; Focus Groups ; Humans ; Methods ; Physical Examination ; Self-Evaluation Programs ; Surveys and Questionnaires