Purpose: While MRI-based tumor regression grade (mrTRG) has shown promise in evaluating pathologic response to concurrent chemoradiotherapy (CCRT) in rectal cancer, its ability to predict pathologic complete response remains limited.This study aimed to enhance mrTRG’s diagnostic performance in predicting ypT0–1N0 status, a key factor in considering non-radical management after CCRT for locally advanced rectal cancer (LARC). Methods: This retrospective study included 430 patients with LARC who underwent radical resection following CCRT at a single referral hospital between April 2018 and September 2024. Multivariable logistic regression was used to identify predictive factors associated with achieving ypT0–1N0 status. The diagnostic performances of mrTRG1–2 alone and in combination with other factors were assessed by comparing sensitivity, specificity, positive-predictive value (PPV), negative-predictive value, and area under the curve (AUC). Results: Ninety-three patients (21.6%) achieved ypT0–1N0. In the multivariable analysis, fungating type, cT1–2, and mrTRG1–2 were independent predictors for ypT0–1N0. Integrating mrTRG with gross tumor type yielded the highest AUC of 0.689 among the combined models. For predicting ypT0–1N0, the combination of mrTRG and gross tumor type improved PPV (79.2% vs. 41.5% for mrTRG alone) while also demonstrating enhanced sensitivity compared with ycT0–1N0, the conventional MRI-based predictor (40.9% vs. 22.6%). Conclusion This study demonstrated that combining mrTRG and gross tumor type improved the PPV of mrTRG in predicting ypT0–1N0 after CCRT in LARC. Further studies are warranted to validate the role of gross tumor type in refining predictive systems for selecting candidates for non-radical treatment.

Purpose: Hungry bone syndrome (HBS) is a common and critical postoperative complication in patients undergoing parathyroidectomy (PTX) for secondary hyperparathyroidism (SHPT) and tertiary hyperparathyroidism (THPT). We aimed to identify clinical predictors of HBS and assess its impact on bone mineral density (BMD) after PTX. Methods: We retrospectively analyzed data of patients with SHPT and THPT who underwent PTX at Asan Medical Center (2010–2022). Clinical characteristics, including biochemical markers and BMD, were investigated. HBS was defined as profound hypocalcemia of less than 8.4 mg/dL (2.1 mmol/L) or prolonged hypocalcemia for more than 4 days after PTX. Results: A total of 91 patients were included: 18 (19.8%) with SHPT and 73 (80.2%) with THPT. Subtotal PTX was performed in 80 patients (87.9%), while 11 patients (12.1%) underwent total PTX with autotransplantation (TPTX + AT). HBS occurred in 31 patients (34.1%), with a higher incidence in patients with SHPT (72.2%) and all patients who underwent TPTX + AT.Patients with HBS required more calcium supplementation and had higher ALP levels at all timepoints (P < 0.001). In the HBS group, BMD improved more significantly in the femur (P = 0.005) and showed a trend towards improvement in the spine (P = 0.059). Risk factors for HBS included younger age, SHPT, and elevated preoperative ALP and intact parathyroid hormone levels. Conclusion HBS is characterized by severe hypocalcemia due to calcium reabsorption into bone after PTX. Identifying risk factors for HBS may promote early risk stratification and tailored perioperative management, including surgical approach, especially for high-risk patients.

Papillary thyroid carcinoma (PTC) has a favorable prognosis. However distant metastases seldom occur and negatively impact patient outcomes. To our knowledge, this is the first report of PTC metastasizing to the rectum, penis, and bladder. We report 2 patients having PTC with metastases to previously unreported sites. The first male patient had PTC with metastases to the rectum and penis, in addition to lung, liver, spleen, and skeletal muscle involvement at the time of initial diagnosis. Surgical pathology reported classic PTC with clear cell features and infiltrative follicular variant. The second female patient had PTC with aggressive lateral neck lymph node metastases at initial surgery. Surgical pathology reported PTC having tall cell variant with rhabdoid components. Subsequent metastases to bladder, lung, brain, vertebrae, and sternum occurred within 2 years. These cases emphasize the importance of early suspicion and thorough evaluation, particularly in aggressive subtypes, as timely detection may improve treatment strategies and patient outcomes. Due to the lack of established guidelines for rare metastatic sites, additional case reports are essential to guide diagnosis and treatment.

Purpose: By utilizing both protein and mRNA expression patterns, we can identify more detailed and diverse immune cells, providing insights into understanding the complex immune landscape in cancer ecosystems. Materials and Methods: This study was performed by obtaining publicly available Cellular Indexing of Transcriptomes and Epitopes by Sequencing (CITE-seq) data of peripheral blood mononuclear cells (PBMCs) from the Gene Expression Omnibus database. A total of 94674 total cells were analyzed, of which 32412 were T cells. There were 228 protein features and 16262 mRNA features in the data.The Seurat package was used for quality control and preprocessing, principal component analysis was performed, and Uniform Manifold Approximation and Projection was used to visualize the clusters. Protein and mRNA levels in the CITE-seq were analyzed. Results: We observed that a subset of T cells in the clusters generated at the protein level divided better. By identifying mRNA markers that were highly correlated with the CD4 and CD8 proteins and cross-validating CD26 and CD99 markers using flow cytometry, we found that CD4 + and CD8+ T cells were better discriminated in PBMCs. Weighted Nearest Neighbor clustering results identified a previously unobserved T cell subset. Conclusion In this study, we used CITE-seq data to confirm that protein expression patterns could be used to identify cells more precisely. These findings will improve our understanding of the heterogeneity of immune cells in the future and provide valuable insights into the complexity of the immune response in health and disease.

Purpose: We aimed to comprehensively analyze the immune cell and stromal components of tumor microenvironment at the single-cell level and identify tumor heterogeneity among the major top-derived oncogene mutations in non-small cell lung cancer (NSCLC) using single-cell RNA sequencing (scRNA-seq) data. Materials and Methods: The scRNA-seq dataset utilized in this study comprised 64369 primary tumor tissue cells from 21 NSCLC patients, focusing on mutations in EGFR, ALK, BRAF, KRAS, TP53, and the wild-type. Results: Tumor immune microenvironment (TIM) analysis revealed differential immune responses across NSCLC mutation subtypes. TIM analysis revealed different immune responses across the mutation subtypes. Two mutation clusters emerged: KRAS, TP53, and EGFR+TP53 mutations (MC1); and EGFR, BRAF, and ALK mutations (MC2). MC1 showed higher tertiary lymphoid structures signature scores and enriched populations of C2-T-IL7R, C3-T/NK-CXCL4, C9-T/NK-NKG, and C1-B-MS4A1 clusters than cluster 2. Conversely, MC2 cells exhibited higher expression levels of TNF, IL1B, and chemokines linked to alternative immune pathways. Remarkably, co-occurring EGFR and TP53 mutations were grouped as MC1. EGFR+TP53 mutations showed upregulation of peptide synthesis and higher synthetic processes, as well as differences in myeloid and T/NK cells compared to EGFR mutations. In T/NK cells, EGFR+TP53 mutations showed a higher expression of features related to cell activity and differentiation, whereas EGFR mutations showed the opposite. Conclusion Our research indicates a close association between mutation types and tumor microenvironment in NSCLC, offering insights into personalized approaches for cancer diagnosis and treatment.

Purpose: We aimed to comprehensively analyze the immune cell and stromal components of tumor microenvironment at the single-cell level and identify tumor heterogeneity among the major top-derived oncogene mutations in non-small cell lung cancer (NSCLC) using single-cell RNA sequencing (scRNA-seq) data. Materials and Methods: The scRNA-seq dataset utilized in this study comprised 64369 primary tumor tissue cells from 21 NSCLC patients, focusing on mutations in EGFR, ALK, BRAF, KRAS, TP53, and the wild-type. Results: Tumor immune microenvironment (TIM) analysis revealed differential immune responses across NSCLC mutation subtypes. TIM analysis revealed different immune responses across the mutation subtypes. Two mutation clusters emerged: KRAS, TP53, and EGFR+TP53 mutations (MC1); and EGFR, BRAF, and ALK mutations (MC2). MC1 showed higher tertiary lymphoid structures signature scores and enriched populations of C2-T-IL7R, C3-T/NK-CXCL4, C9-T/NK-NKG, and C1-B-MS4A1 clusters than cluster 2. Conversely, MC2 cells exhibited higher expression levels of TNF, IL1B, and chemokines linked to alternative immune pathways. Remarkably, co-occurring EGFR and TP53 mutations were grouped as MC1. EGFR+TP53 mutations showed upregulation of peptide synthesis and higher synthetic processes, as well as differences in myeloid and T/NK cells compared to EGFR mutations. In T/NK cells, EGFR+TP53 mutations showed a higher expression of features related to cell activity and differentiation, whereas EGFR mutations showed the opposite. Conclusion Our research indicates a close association between mutation types and tumor microenvironment in NSCLC, offering insights into personalized approaches for cancer diagnosis and treatment.

Purpose: Silent pheochromocytoma refers to tumors without signs and symptoms of catecholamine excess. This study aimed to clarify the clinical, radiological characteristics, and perioperative features of silent pheochromocytomas diagnosed after adrenalectomy for adrenal incidentaloma. Methods: Medical records of patients who underwent adrenalectomy for adrenal incidentaloma and were subsequently diagnosed with silent pheochromocytoma between January 2000 and December 2020 were retrospectively reviewed for demographic, diagnostic, surgical, and pathological findings. Results: Of the 130 patients who underwent adrenalectomy for incidentaloma, 8 (6.1%) were diagnosed with silent pheochromocytoma. Almost all patients had no hypertensive symptoms and their baseline hormonal levels remained within normal ranges. All patients exhibited tumor size >4 cm, precontrast Hounsfield unit >10, and absolute washout <60%. Intraoperative hypertensive events were noted in 2 patients (25.0%) in whom antiadrenergic medications were not administered. All patients in the intraoperative hypertensive event group exhibited atypical features on CT, whereas 83.3% of patients in the non-intraoperative hypertensive event group showed atypical features on CT imaging. Conclusion Silent pheochromocytomas share radiological traits with malignant adrenal tumors. Suspicious features on CT scans warrant surgical consideration for appropriate treatment. Administering alpha-blockers can enhance hemodynamic stability during adrenalectomy in suspected silent pheochromocytoma cases.

Purpose: Adrenocortical carcinoma (ACC) is a rare primary carcinoma originating in the adrenal gland with a poor prognosis and a high recurrence rate. This study evaluated the risk factors associated with recurrence in patients with early stage ACC after curative surgical resection. Methods: The present study retrospectively evaluated the risk factors for recurrence in 38 patients with stages 1 and 2 ACC who underwent curative resection between 1995 and 2020. Results: Recurrence was observed in 21 patients (55.3%), with no significant difference between stages 1 and 2 ACC (P = 0.640). The overall recurrence rate was higher in patients who underwent minimally invasive surgery than open adrenalectomy (71.4% vs. 51.6%). Of the 33 patients with gross tumor margins negative for malignancy, 16 (48.5%) experienced tumor recurrence, and all 5 patients with positive and unknown gross resection margins had recurrence.Recurrences were observed in 14 of the 30 patients (46.7%) negative for pathologic resection margins, 6 of the 7 patients (85.7%) with pathologically indeterminate margins, and 1 patient with pathologically positive margins. Conclusion The recurrence rates are high even in patients with early stage ACC, being higher in patients who undergo minimally invasive surgery than open adrenalectomy. Obtaining clear resection margins during surgery may reduce tumor recurrence; however, gross or pathologic margin safety was not a secure factor in preventing recurrence. None of the factors analyzed was a definitive predictor of poor prognosis.

Background: Sodium-dependent glucose cotransporter 2 (SGLT2) mediates glucose reabsorption in the renal proximal tubules, and SGLT2 inhibitors are used as therapeutic agents for treating type 2 diabetes mellitus. This study aimed to elucidate the effects and mechanisms of SGLT2 inhibition on hepatic glucose metabolism in both serum deprivation and serum supplementation states. Methods: Huh7 cells were treated with the SGLT2 inhibitors empagliflozin and dapagliflozin to examine the effect of SGLT2 on hepatic glucose uptake. To examine the modulation of glucose metabolism by SGLT2 inhibition under serum deprivation and serum supplementation conditions, HepG2 cells were transfected with SGLT2 small interfering RNA (siRNA), cultured in serum-free Dulbecco’s modified Eagle’s medium for 16 hours, and then cultured in media supplemented with or without 10% fetal bovine serum for 8 hours. Results: SGLT2 inhibitors dose-dependently decreased hepatic glucose uptake. Serum deprivation increased the expression levels of the gluconeogenesis genes peroxisome proliferator-activated receptor gamma co-activator 1 alpha (PGC-1α), glucose 6-phosphatase (G6pase), and phosphoenolpyruvate carboxykinase (PEPCK), and their expression levels during serum deprivation were further increased in cells transfected with SGLT2 siRNA. SGLT2 inhibition by siRNA during serum deprivation induces nuclear localization of the transcription factor forkhead box class O 1 (FOXO1), decreases nuclear phosphorylated-AKT (p-AKT), and p-FOXO1 protein expression, and increases phosphorylated-adenosine monophosphate-activated protein kinase (p-AMPK) protein expression. However, treatment with the AMPK inhibitor, compound C, reversed the reduction in the protein expression levels of nuclear p- AKT and p-FOXO1 and decreased the protein expression levels of p-AMPK and PEPCK in cells transfected with SGLT2 siRNA during serum deprivation. Conclusion These data show that SGLT2 mediates glucose uptake in hepatocytes and that SGLT2 inhibition during serum deprivation increases gluconeogenesis via the AMPK/AKT/FOXO1 signaling pathway.

This report presents the latest statistics on the stroke population in South Korea, sourced from the Clinical Research Collaborations for Stroke in Korea-National Institute for Health (CRCS-K-NIH), a comprehensive, nationwide, multicenter stroke registry. The Korean cohort, unlike western populations, shows a male-to-female ratio of 1.5, attributed to lower risk factors in Korean women. The average ages for men and women are 67 and 73 years, respectively.Hypertension is the most common risk factor (67%), consistent with global trends, but there is a higher prevalence of diabetes (35%) and smoking (21%). The prevalence of atrial fibrillation (19%) is lower than in western populations, suggesting effective prevention strategies in the general population. A high incidence of large artery atherosclerosis (38%) is observed, likely due to prevalent intracranial arterial disease in East Asians and advanced imaging techniques.There has been a decrease in intravenous thrombolysis rates, from 12% in 2017–2019 to 10% in 2021, with no improvements in door-to-needle and door-to-puncture times, worsened by the coronavirus disease 2019 pandemic. While the use of aspirin plus clopidogrel for noncardioembolic stroke and direct oral anticoagulants for atrial fibrillation is well-established, the application of direct oral anticoagulants for non-atrial fibrillation cardioembolic strokes in the acute phase requires further research. The incidence of early neurological deterioration (13%) and the cumulative incidence of recurrent stroke at 3 months (3%) align with global figures. Favorable outcomes at 3 months (63%) are comparable internationally, yet the lack of improvement in dependency at 3 months highlights the need for advancements in acute stroke care.