Rationale: There have been many reports of non-thyroidal lesions which can be mistaken for thyroidal lesions on ultrasound (US) examination. However, it is not known that pyriform sinus fistula (PSF) can manifest as an incidental thyroid nodule and cause serious complication on fine-needle aspiration (FNA). Patient concerns: We present a 34-year-old man with PSF incidentally detected on US. US examination showed hypoechoic nodule with several bright echogenic spots at the uppermost part of left thyroid gland. With the suspicion of thyroid cancer, although there would have been some morphologic changes between the 2 US examinations, FNA was performed. Diagnoses: Cytologic specimen revealed some clusters of ciliated columnar cells mixed with inflammatory and lymphoid cells. On computed tomography (CT) before FNA, there were tiny air bubbles within the thyroid nodule. Laryngoscopy revealed fistula originating from the pyriform sinus. Interventions: After FNA, he had to undergo tracheostomy and removal of abscess due to infectious complication. Outcomes: The deep neck abscesses and infections were controlled after the treatment. At 1 year after FNA, successful chemocauterization with 40% trichloracetic acid solution was performed for PSF found on laryngoscopy. Lessons: PSF can manifest as an incidental thyroid nodule mimicking thyroid cancer. Special care should be taken when FNA is planned for the nodule with air foci and morphologic changeability at the uppermost part of left thyroid gland.
Abstract The heterogeneity of Parkinson's disease (PD) is increasingly recognized as an important aspect of understanding the disorder. Among the factors contributing to this heterogeneity, ethnic differences are primary sources, significantly influencing the likelihood of PD developing and its initial symptoms' nature. While there have been numerous reports related to PD in East Asia, there has been a lack of contribution from single-cell (or nucleus) transcriptome studies, which have been making significant contributions to understanding PD. In this study, a total of 33,293 nuclei obtained from the substantia nigra (SN) of confirmed pathological PD and control patients in South Korea were profiled, revealing 8 different cell types through cluster analysis. Monocle-based pseudotime analysis identified two disease-associated trajectories for each astrocyte and microglia and identified genes that differentiate them. Interestingly, we uncovered the inflammatory intervention in the early PD-associated transition in microglia and identified the molecular features of this intermediate state of microglia. In addition, gene regulatory networks (GRNs) based on TENET analysis revealed the detrimental effect of an HSPA5-led module in microglia and MSRB3- and HDAC8- led modules specifying the two different astrocyte trajectories. In SN neurons, we observed population changes, a decrease in dopaminergic and glutamatergic neurons and a proportional increase in GABAergic neurons. By deconvolution in spatial transcriptome obtained the PD sample, we confirmed spatiotemporal heterogeneity of neuronal subpopulations and PD-associated progressive gliosis specific to dopaminergic nuclei, SN and ventral tegmental areas (VTAs). In conclusion, our approach has enabled us to identify the genetic and spatial characterization of neurons and to demonstrate different glial fates in PD. These findings advance our molecular understanding of cell type-specific changes in the progression of Korean PD, providing an important foundation for predicting and validating interventions or drug effects for future treatments.
Abstract Medullary thyroid carcinoma (MTC) is a rare thyroid malignancy derived from the parafollicular C cells of thyroid gland. It features relatively aggressive biologic behavior among thyroid cancers, but its genomic landscape has not yet been fully explored. Here, we conducted multi-omics data (whole genome sequencing (WGS), and bulk (bulk RNA-seq) or single nucleus RNA sequencing (snRNA-seq)) on MTC, and found genetic characteristics of MTC and a new gene signature predicting aggressiveness of tumors. WGS was performed for 35 pairs of tumor specimens and normal thyroid tissues from 30 patients. And bulk RNA-seq for 59 samples (20 normal thyroid tissues, 26 primary MTCs, 9 recurred lymph nodes, and 4 metastatic lymph nodes) and snRNA-seq for 3 primary MTCs, and 2 recurred/metastatic lymph nodes were also performed. In WGS results, we verified driver mutations, including RET, RAS, and BRAF. Four patients were classified as germline RET mutations based on familial history. Somatic RET M918T mutations were occurred in 8 patients, 9 patients were observed other RET mutations. Also, we observed other somatic mutations such as HRAS and BRAF. Seven patients occurred somatic HRAS mutations (Q61L, Q61R, G13R, A11 and G15), and somatic BRAF mutations (G469A, K601E) were observed in two patients. We found broad-level copy-number alterations in ~50% of patients, and we also found a patient who shows whole-genome duplication. The copy-number alteration was associated with aggressive phenotype in MTC. In addition, we found complex rearrangements such as microhomology-mediated break-induced replication in five patients. Interestingly, we found intra-tumoral heterogeneity of several genes related to C cell differentiation through snRNA-seq analysis by comparing clusters of tumor cells. Using the genes, we calculated the C cell differentiation score of the samples with bulk RNA-seq by GSVA algorithm. This score was related to poor clinical characteristics such as recurrence. In conclusion, multi-omics profiling of MTC reveals that copy number alterations and C cell differentiation status are the important biomarkers for cancer aggressiveness. Citation Format: Seong Eun Lee, Seongyeol Park, Shinae Yi, Joonoh Lim, Na Rae Choi, JungHak Kwak, June-Young Koh, Boram Yi, Jaemo Koo, Jae Won Chang, Young Seok Ju, Bon Seok Koo, Jin Man Kim, Young Joo Park, Minho Shong, Eun Kyung Lee, Jae Kyung Won, Yea Eun Kang, Kyu Eun Lee. Genomic and transcriptomic characterization of medullary thyroid cancer. [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 6069.
Objective: The purpose of this study was to investigate the effect of driving simulator training on the driving performance and self-efficacy of paraplegic patients with spinal cord injury. Method: Driving simulator training was provided to 12 participants with within subjects design, three sessions of basic driving, seven sessions of driving on the driving simulator. After training, performance time and operational performance scores, self-efficacy were analyzed. Results: This study found that the intervention by the driving simulator had statistically significant effects on driving time, performance error, ‘Sudden start’, ‘No neutral gear when stopping’, and ‘Speed violation’ and ‘Social self-efficacy’ of paraplegic spinal cord injury patients (p<.05). Conclusion: Driving simulator training can be a strategy to improve driving performance and social self-efficacy of paraplegic patients with spinal cord injury. Also, patients need sufficient sessions more than 10 times of driving simulator training.
We report a case of spinal ependymoma with ZFTA-YAP1 fusion, occurring in a 5-year-old boy who complained of back pain. It was high-grade ependymoma, developed in the spinal cord at the level of T9-12. Since ZFTA-YAP1 fusion-positive ependymoma has never been reported in the spinal cord, this case is exceptional and worth reporting because the anatomical location, genetics, and epigenetics are important parameters in the classification of the ependymal tumor. This is the first case of spinal ependymoma harboring ZFTA-fusion to be diagnosed by NGS and Sanger studies to the best of our knowledge.
Abstract To evaluate whether the cerebral blood volume (CBV) measurement with leakage correction from dynamic susceptibility contrast perfusion weighted imaging can be useful in predicting prognosis for primary central nervous system lymphoma (PCNSL). 46 PCNSL patients were included and classified by radiation therapy (RT) stratification into RT (n = 30) and non-RT (n = 16) groups. The corresponding histogram parameters of normalized CBV (nCBV) maps with or without leakage correction were calculated on contrast-enhanced T1 weighted image (CE T1WI) or on fluid attenuated inversion recovery image. The 75 th percentile nCBV with leakage correction based on CE T1WI (T1 nCBVL 75% ) had a significant difference between the short and long progression free survival (PFS) subgroups of the RT group and the non-RT group, respectively. Based on the survival analysis, patients in the RT group with high T1 nCBVL 75% had earlier progression than the others with a low T1 nCBVL 75% . However, patients in the non-RT group with a high T1 nCBVL 75% had slower progression than the others with a low T1 nCBVL 75% . Based on RT stratification, the CBV with leakage correction has potential as a noninvasive biomarker for the prognosis prediction of PCNSL to identify high risk patients and it has a different correlation with the PFS based on the presence of combined RT.
Objective Pheochromocytoma and paraganglioma (extra-adrenal pheochromocytoma) are rare neuroendocrine tumors that arise from the neuroendocrine cells. Chronic hypoxia is known as a possible cause, and a strong link between cyanotic congenital heart disease and these tumors has been reported. However, reports of phechromocytoma/paraganglioma in Fontan patients were scarce. We herein report seven cases of phechromocytoma/paraganglioma after Fontan operation at a single tertiary center. Methods We retrospectively reviewed medical records and imaging studies who diagnosed as phechromocytoma/paraganglioma after Fontan operation in Seoul National University Children's Hospital. Results Seven patients were identified during follow-up after Fontan operation, and the prevalence was 2.5% among Fontan patients greater than 10 years old on active follow-up. Three patients were diagnosed as phechromocytoma and 4 patients as paraganglioma. Median time interval between Fontan operation and diagnosis of pheochromocytoma/paraganglioma was 21.4 years (range, 10.4–29.7 years). Resting percutaneous oxygen saturation varied from 77% to 94%. All patients underwent complete tumor resection. Phechromocytoma recurred in two patients, of whom one patient died at the age of 18 years due to the tumor progression with multiple metastasis and aggravation of heart failure with profound cyanosis. Pheochromocytoma/paraganglioma developed after hepatocellular carcinoma in two patients. Conclusion Phechromocytoma/paraganglioma could occur in Fontan patients more than expected. Because it is curable by tumor resection during its early phase, early diagnosis and treatment of pheochromocytoma are crucial in Fontan patients not to make hemodynamic deterioration and aggravation of heart failure.
Abstract The heterogeneity of Parkinson’s disease (PD) is increasingly recognized as an important aspect of understanding the disorder. Among the factors contributing to this heterogeneity, ethnic differences are primary sources, significantly influencing the likelihood of PD developing and its initial symptoms’ nature. While there have been numerous reports related to PD in East Asia, there has been a lack of contribution from single-cell (or nucleus) transcriptome studies, which have been making significant contributions to understanding PD. In this study, a total of 33,293 nuclei obtained from the substantia nigra (SN) of confirmed pathological PD and control patients in South Korea were profiled, revealing 8 different cell types through cluster analysis. Monocle-based pseudotime analysis identified two disease-associated trajectories for each astrocyte and microglia and identified genes that differentiate them. Interestingly, we uncovered the inflammatory intervention in the early PD-associated transition in microglia and identified the molecular features of this intermediate state of microglia. In addition, gene regulatory networks (GRNs) based on TENET analysis revealed the detrimental effect of an HSPA5- led module in microglia and MSRB3- and HDAC8- led modules specifying the two different astrocyte trajectories. In SN neurons, we observed population changes, a decrease in dopaminergic and glutamatergic neurons and a proportional increase in GABAergic neurons. By deconvolution in spatial transcriptome obtained the PD sample, we confirmed spatiotemporal heterogeneity of neuronal subpopulations and PD-associated progressive gliosis specific to dopaminergic nuclei, SN and ventral tegmental areas (VTAs). In conclusion, our approach has enabled us to identify the genetic and spatial characterization of neurons and to demonstrate different glial fates in PD. These findings advance our molecular understanding of cell type-specific changes in the progression of Korean PD, providing an important foundation for predicting and validating interventions or drug effects for future treatments.
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