Background: We explored the utility of a small multi-gene DNA panel for assessing molecular profiles of thyroid nodules and influencing clinical decisions by comparing outcomes between tested and untested nodules. Methods: Between April 2022 and May 2023, we prospectively performed fine-needle aspiration (FNA) with gene testing via DNA panel of 11 genes (BRAF, RAS [NRAS, HRAS, KRAS], EZH1, DICER1, EIF1AX, PTEN, TP53, PIK3CA, TERT promoter) in 278 consecutive nodules (panel group). Propensity score-matching (1:1) was performed with 475 nodules that consecutively underwent FNA without gene testing between January 2021 and December 2021 (control group). Results: In the panel group, positive call rate for mutations was 41.7% (BRAF 16.2%, RAS 12.6%, others 11.5%, double mutation 1.4%) for all nodules, and 40.0% (BRAF 4.3%, RAS 19.1%, others 15.7%, double mutation 0.9%) for indeterminate nodules. Benign call rate was 69.8% for all nodules, and 75.7% for indeterminate nodules. In four nodules, additional TP53 (in addition to BRAF or EZH1) or PIK3CA (in addition to BRAF or TERT) mutations were co-detected. Sensitivity, specificity, positive predictive value, and negative predictive value were 80.0%, 53.3%, 88.1%, 38.1% for all nodules, and 78.6%, 45.5%, 64.7%, 62.5% for indeterminate nodules, respectively. Panel group exhibited lower surgical resection rates than the control group for all nodules (27.0% vs. 52.5%, P<0.001), and indeterminate nodules (23.5% vs. 68.2%, P<0.001). Malignancy risk was significantly different between the panel and control groups (81.5% vs. 63.9%, P=0.008) for all nodules. Conclusion Our panel aids in managing thyroid nodules by providing information on malignancy risk based on mutations, potentially reducing unnecessary surgery in benign nodules or patients with less aggressive malignancies.

Purpose: This study evaluated epidermal cyst elasticity using multiple parameters of strain elastography (SE) and shear wave elastography (SWE) and assessed the reproducibility of each parameter. Methods: This retrospective study included 73 patients with epidermal cysts who underwent SE and SWE. SE scores were classified as 1-4 according to elasticity. The strain ratio was evaluated using the elasticity ratio of lesions and adjacent subcutaneous fat tissue. For SWE, the shear wave velocity (m/s), elasticity (kPa) according to the Young modulus, velocity ratio, and elasticity ratio were evaluated. All values were measured twice. The reproducibility of SE and SWE measurements was assessed. The relationships among SE and SWE measurements were evaluated. Results: The strain ratio on SE images showed good reproducibility (intra-class correlation coefficient [ICC]=0.789), and SE scores showed substantial reproducibility (kappa=0.753 and kappa=0.758 for readers 1 and 2, respectively). Moderate reproducibility was found for shear wave velocity and elasticity (ICC=0.750 and ICC=0.648, respectively), as well as for the shear wave velocity of the reference tissue and velocity ratio (ICC=0.747 and ICC=0.713, respectively). All SE scores were positively correlated with the strain ratio (P<0.001). The strain ratio in the second SE session was significantly correlated with the elasticity ratio and velocity ratio in the first SWE session (r=0.245, P=0.037; r=0.243, P=0.038, respectively). Other variables were not correlated. Conclusion SE and SWE parameters of epidermal cysts showed moderate to good reproducibility. The strain ratio on SE showed good reproducibility and could provide relatively objective and consistent measurements of epidermal cyst elasticity.

Fascicular involvement of the median nerve trunk in the upper arm is uncommon in cases of peripheral neuropathy, and its symptoms are consistent with those of anterior interosseous nerve (AIN) syndrome. We report three cases of focal anterior interosseous fascicular involvement in the median nerve trunk presenting as AIN palsy. Our report emphasizes the unique ultrasonographic and magnetic resonance imaging (MRI) features of swelling, hourglass-like constriction and torsion, and entwinement of the nerve fascicle of the dorsal region of the median nerve, which were confirmed surgically. On MRI, all patients showed denervation changes in the AIN territory, as well as in the median nerve territory, without compressing structures.

Alzheimer's Disease (AD) is a progressive neurodegenerative disease, which is pathologically defined by the accumulation of amyloid plaques and hyper-phosphorylated tau aggregates in the brain. Mitochondrial dysfunction is also a prominent feature in AD, and the extracellular Aβ and phosphorylated tau result in the impaired mitochondrial dynamics. In this study, we generated an induced pluripotent stem cell (iPSC) line from an AD patient with amyloid precursor protein (APP) mutation (Val715Met; APP-V715M) for the first time. We demonstrated that both extracellular and intracellular levels of Aβ were dramatically increased in the APP-V715M iPSC-derived neurons. Furthermore, the APP-V715M iPSC-derived neurons exhibited high expression levels of phosphorylated tau (AT8), which was also detected in the soma and neurites by immunocytochemistry. We next investigated mitochondrial dynamics in the iPSC-derived neurons using Mito-tracker, which showed a significant decrease of anterograde and retrograde velocity in the APP-V715M iPSC-derived neurons. We also found that as the Aβ and tau pathology accumulates, fusion-related protein Mfn1 was decreased, whereas fission-related protein DRP1 was increased in the APP-V715M iPSC-derived neurons, compared with the control group. Taken together, we established the first iPSC line derived from an AD patient carrying APP-V715M mutation and showed that this iPSC-derived neurons exhibited typical AD pathological features, including a distinct mitochondrial dysfunction.
Alzheimer Disease ; Amyloid ; Brain ; Carisoprodol ; Humans ; Immunohistochemistry ; Mitochondrial Dynamics ; Neurites ; Neurodegenerative Diseases ; Neurons ; Pathology ; Plaque, Amyloid ; Pluripotent Stem Cells

OBJECTIVE: To examine (1) the degree of reduction of passive range of motion (PROM) on the affected side compared to that on the unaffected side and (2) the degree of increase in PROM following intra-articular corticosteroid injection (IACI) in patients with frozen shoulder.METHOD: The medical records of 120 patients with frozen shoulder were retrospectively reviewed. PROM of the unaffected and affected shoulder (flexion, extension, abduction, internal rotation, external rotation) was compared, and changes in PROM of the affected shoulder after a single IACI (triamcinolone 20 mg) were evaluated after 12 weeks.RESULTS: At the time of diagnosis, PROM of the affected shoulder was most limited in external rotation, followed by internal rotation, abduction, extension, and flexion, compared to that of the unaffected shoulder. Compared to before IACI, PROM of external rotation demonstrated the greatest increase compared to all the other movements after IACI.CONCLUSION: Limitation in PROM of the frozen shoulder at the time of diagnosis was greatest for external rotation. Moreover, external rotation experienced the greatest improvement after IACI. Our findings should help to further clarify the clinical characteristics of frozen shoulder, aid in its diagnosis, and allow the prediction of the effects of IACI.
Adrenal Cortex Hormones ; Bursitis ; Diagnosis ; Follow-Up Studies ; Humans ; Injections, Intra-Articular ; Medical Records ; Methods ; Range of Motion, Articular ; Retrospective Studies ; Shoulder

PURPOSE: Thyroglobulin (Tg) may be released from damaged residual thyroid tissues after radioactive iodine (RAI) therapy in patients with differentiated thyroid carcinoma (DTC). We investigated whether altered levels of serum Tg after recombinant human thyrotropin (rhTSH)-aided RAI therapy could be a prognostic marker in patients with DTC.METHODS: We evaluated 68 patients who underwent RAI therapy after total thyroidectomy. Serum Tg levels were measured just before RAI administration (D0Tg) and 7 days after RAI therapy (D7Tg). Patients with a D0Tg level greater than 2.0 ng/mL were excluded to more precisely evaluate the injury effect of RAI in small remnant tissues. The ratioTg was defined as the D7Tg level divided by that on D0Tg. The therapeutic responses were classified as acceptable or non-acceptable. Finally, we investigated which clinicopathologic parameters were associated with therapeutic response.RESULTS: At the follow-up examination, an acceptable response was observed in 50 patients (73.5%). Univariate analysis revealed significant differences in N stage (P = 0.003) and ratioTg (acceptable vs. non-acceptable responses, 21.9 ± 33.6 vs. 3.8 ± 6.5; P = 0.006). In multivariate analysis, only ratioTg significantly predicted an acceptable response (odds ratio 1.104; 95% confidence interval 1.005–1.213; P = 0.040). A ratioTg above 3.5 predicted an acceptable response with a sensitivity of 66.0%, specificity of 83.3%, and accuracy of 70.6% (area under the curve = 0.718; P = 0.006).CONCLUSIONS: Altered levels of serum Tg after RAI therapy, calculated as the ratioTg (D7Tg/D0Tg), significantly predicted an acceptable response in patients with DTC.
Follow-Up Studies ; Humans ; Iodine ; Multivariate Analysis ; Sensitivity and Specificity ; Thyroglobulin ; Thyroid Gland ; Thyroid Neoplasms ; Thyroidectomy ; Thyrotropin

Disease modeling of Alzheimer's disease (AD) has been hampered by the lack of suitable cellular models while animal models are mainly based on the overexpression of AD-related genes which often results in an overemphasis of certain pathways and is also confounded by aging. In this study, we therefore developed and used induced pluripotent stem cell (iPSC) lines from a middle-aged AD patient with a known presenilin 1 (PSEN1) mutation (Glu120Lys; PS1-E120K) and as a control, an elderly normal subject. Using this approach, we demonstrated that the extracellular accumulation of Aβ was dramatically increased in PS1-E120K iPSC-derived neurons compared with the control iPSC line. PS1-E120K iPSC-derived neurons also exhibited high levels of phosphorylated tau, as well as mitochondrial abnormalities and defective autophagy. Given that the effect of aging is lost with iPSC generation, these abnormal cellular features are therefore indicative of PSEN1-associated AD pathogenesis rather than primary changes associated with aging. Taken together, this iPSC-based approach of AD modeling can now be used to better understand AD pathogenesis as well as a tool for drug discovery.
Aged ; Aging ; Alzheimer Disease* ; Autophagy ; Cerebellar Ataxia* ; Drug Discovery ; Humans ; Models, Animal ; Neurons ; Pluripotent Stem Cells ; Presenilin-1 ; Stem Cells

PURPOSE: Thyroglobulin (Tg) may be released from damaged residual thyroid tissues after radioactive iodine (RAI) therapy in patients with differentiated thyroid carcinoma (DTC). We investigated whether altered levels of serum Tg after recombinant human thyrotropin (rhTSH)-aided RAI therapy could be a prognostic marker in patients with DTC. METHODS: We evaluated 68 patients who underwent RAI therapy after total thyroidectomy. Serum Tg levels were measured just before RAI administration (D0Tg) and 7 days after RAI therapy (D7Tg). Patients with a D0Tg level greater than 2.0 ng/mL were excluded to more precisely evaluate the injury effect of RAI in small remnant tissues. The ratioTg was defined as the D7Tg level divided by that on D0Tg. The therapeutic responses were classified as acceptable or non-acceptable. Finally, we investigated which clinicopathologic parameters were associated with therapeutic response. RESULTS: At the follow-up examination, an acceptable response was observed in 50 patients (73.5%). Univariate analysis revealed significant differences in N stage (P = 0.003) and ratioTg (acceptable vs. non-acceptable responses, 21.9 ± 33.6 vs. 3.8 ± 6.5; P = 0.006). In multivariate analysis, only ratioTg significantly predicted an acceptable response (odds ratio 1.104; 95% confidence interval 1.005–1.213; P = 0.040). A ratioTg above 3.5 predicted an acceptable response with a sensitivity of 66.0%, specificity of 83.3%, and accuracy of 70.6% (area under the curve = 0.718; P = 0.006). CONCLUSIONS Altered levels of serum Tg after RAI therapy, calculated as the ratioTg (D7Tg/D0Tg), significantly predicted an acceptable response in patients with DTC.

A yeast-like organism was isolated from a urine sample of a 6-year-old neutered male miniature poodle dog with urinary tract infection, diabetes ketoacidosis, and acute pancreatitis. We identified the yeast-like organism to be Candida glabrata and found that this fungus was highly resistant to azole antifungal drugs. To understand the mechanism of azole resistance in this isolate, the sequences and expression levels of the genes involved in drug resistance were analyzed. The results of our analysis showed that increased drug efflux, mediated by overexpression of ATP transporter genes CDR1 and PDH1, is the main cause of azole resistance of the C. glabrata isolated here.
Adenosine Triphosphate ; Animals ; Candida glabrata* ; Candida* ; Child ; Danazol* ; Diabetes Mellitus* ; Dogs* ; Drug Resistance ; Fungi ; Humans ; Ketosis ; Male ; Pancreatitis ; Urinary Tract Infections ; Urinary Tract*

Reconstruction of a ruptured anterior cruciate ligament (ACL) is a well-established procedure for repair of ACL injury. Despite improvement of surgical and rehabilitation techniques over the past decades, up to 25% of patients still fail to regain satisfactory function after an ACL reconstruction. With development of CT imaging techniques for reducing metal artifacts, multi-planar reconstruction, and three-dimensional reconstruction, early post-operative imaging is increasingly being used to provide immediate feedback to surgeons regarding tunnel positioning, fixation, and device placement. Early post-operative radiography and CT imaging are easy to perform and serve as the baseline examinations for future reference.
Anterior Cruciate Ligament Reconstruction* ; Anterior Cruciate Ligament* ; Artifacts ; Humans ; Knee ; Radiography ; Rehabilitation ; Surgeons