Purpose: Human epidermal growth factor receptor 2 (HER2) is amplified or overexpressed in various malignancies, including breast and gastric cancers, and is associated with poor prognosis. Although HER2-targeted therapies, such as trastuzumab, improve outcomes in HER2-positive tumors, resistance often develops, and HER2-low tumors remain largely untargeted. Trastuzumab deruxtecan (T-DXd; DS-8201a) is a HER2-targeted antibody-drug conjugate with potent activity in HER2-positive and HER2-low tumors. This study evaluates its antitumor mechanisms and efficacy in HER2-positive, HER2-low, and homologous recombination deficiency (HRD)–associated models. Materials and Methods: Effects of T-DXd were assessed in cancer cell lines with diverse HER2 expression and HRD status. In vivo efficacy was evaluated using a xenograft model derived from HER2-low SNU-601 gastric cancer cells. Results: T-DXd reduced HER2 phosphorylation and downstream signaling (AKT, ERK) in HER2-positive cells. It induced DNA damage accumulation, as evidenced by increased γH2AX and p-Chk1 expression, and triggered apoptosis through cleaved poly(ADP-ribose) polymerase and caspase-3 activation, confirmed by annexin V staining. Similar effects were observed in HER2-low cells, with greater sensitivity in HRD cells. In xenografts, T-DXd reduced tumor volume by up to 80% at 4 mg/kg and 10 mg/kg. Histological analyses showed decreased Ki-67 and increased apoptosis. Furthermore, T-DXd induced G2/M cell cycle arrest and nuclear anaplasia, suggesting disruption of chromosomal stability as a potential antitumor mechanism. No significant toxicity, including body weight loss, was observed. Conclusion These findings highlight T-DXd’s effectiveness in HER2-low and HRD tumors, supporting its broader clinical application, including strategies targeting DNA damage repair pathways.

Objective: : Korea’s healthcare system and policy promotes early, actively stroke treatment to improve prognosis. This study represents stroke epidemiology and outcomes in Korea. Methods: : This study investigated data from the Acute Stroke Assessment Registry. The registry collects data from over 220 hospitals nationwide, focusing on quality stroke service management. Data analysis included patient demographics, stroke severity assessment, and discharge prognosis measurement using standardized scales. Results: : Eighty-six thousand five hundred sixty-eight acute stroke patients were collected with demographic and clinical characteristics during 18 months from 2016, 2018, and between 2020 to 2021, focusing on acute subarachnoid hemorrhage (SAH), acute intracerebral hemorrhage (ICH), and acute ischemic stroke. Of these 86568 patients, 8.3% was SAH, 16.3% ICH, and 74.9% ischemic stroke. Trends showed decreasing SAH and increasing ICH cases over the years. 68.3% stroke patients had the clear onset time. 49.6% stroke patients arrived within 4.5 hours of symptom onset, with more patients treated at general hospitals. Good functional outcomes at discharge was obtained with 58.3% of acute stroke patients, 55.9% of SAH patients, 34.6% of ICH patients, and 63.8% of ischemic stroke patients. Conclusion : The results showed that ischemic stroke was the most common subtype, followed by ICH and SAH. Prognosis differed among subtypes, with favorable outcomes more common in ischemic stroke and SAH compared to ICH.

Neuromyelitis optica spectrum disorder (NMOSD) is a rare inflammatory disease that most often affects the optic nerves and spinal cord. We describe a case of 36-year-old woman presented at 13 weeks of gestation with 4 extremities paresthesia and weakness that had lasted for two months at her first visit to our hospital. She had two previous uncomplicated full-term vaginal deliveries and no significant medical or family history. Spine magnetic resonance imaging (MRI) showed extensive cervical cord lesion and aquaporin-4 antibodies were strongly positive, confirming the diagnosis of NMOSD. Initial management with high-dose corticosteroids and plasmapheresis was done and she showed substantial improvement, but she revisited hospital at 26 weeks of gestational age due to visual disturbance and aggravated weakness. Relapse of NMOSD was confirmed by spine MRI, so rituximab therapy was initiated at 28 weeks of gestational age for prevention of recurrence.The patient showed clinical improvement with no adverse effects and relapse of symptoms. She successfully delivered a healthy male infant at 39 weeks and 3 days of gestational age through uncomplicated vaginal delivery. This case demonstrates successful management of new-onset NMOSD during pregnancy using a multi-modal treatment approach including rituximab.

Objective: To comprehensively assess the relationship between nerve conduction study (NCS), sympathetic skin response (SSR), and demographic factors in patients with diabetic neuropathy, exploring potential risk factors and mechanisms. Methods: A retrospective study (N=184) included patients diagnosed with type 2 diabetes mellitus undergoing NCS and SSR. Demographic, clinical, and laboratory data were analyzed. Patients were categorized by diabetic peripheral neuropathy (DPN) and SSR stages for comparative analysis. Results: HbA1c levels correlated with DPN progression. SSR stages exhibited age-related differences. Height correlated with DPN but not SSR stages. Body mass index showed no significant differences. Conclusion While DPN progression correlated with glycemic control and duration of diabetes, SSR was influenced by age. Unexpectedly, cholesterol levels remained within the normal range, challenging established concepts. Understanding these relationships is crucial for interpreting test results and developing targeted interventions for diabetic neuropathy.

Tofacitinib, which is used to treat rheumatoid arthritis (RA), is primarily metabolized by the hepatic cytochrome P450 (CYP) enzymes, CYP3A1/2 and CYP2C11. Acetaminophen (APAP), which is frequently used for pain relief in patients with RA, can induce acute liver injury (ALI) when taken in excess, profoundly affecting drug metabolism. Resveratrol (RVT) is a polyphenolic compound with hepatoprotective properties. This study investigated the protective effects of RVT against APAP-induced ALI in rats, and explored its influence on the pharmacokinetics of tofacitinib. In ALI rats, both intravenous and oral administration of tofacitinib resulted in a significant (207% and 181%) increase in the area under the plasma concentration-time curve (AUC), primarily driven by a substantial reduction (66.1%) in non-renal clearance (CLNR) compared to that in control (CON) rats. Notably, RVT administration in ALI rats provided effective liver protection, partially restoring liver function, as evidenced by normalized glutamate oxaloacetate transaminase levels and the pharmacokinetic parameters, AUC and CLNR, closer to those observed in untreated CON rats (117% and 81.9%, respectively). These findings highlight the importance of considering the potential interactions between RVT or polyphenol-rich natural products and medications in patients with ALI in clinical practice.

Purpose: Considering the high disease burden and unique features of Asian patients with breast cancer (BC), it is essential to have a comprehensive view of genetic characteristics in this population. An institutional targeted sequencing platform was developed through the Korea Research-Driven Hospitals project and was incorporated into clinical practice. This study explores the use of targeted next-generation sequencing (NGS) and its outcomes in patients with advanced/metastatic BC in the real world. Materials and Methods: We reviewed the results of NGS tests administered to BC patients using a customized sequencing platform—FiRST Cancer Panel (FCP)—over 7 years. We systematically described clinical translation of FCP for precise diagnostics, personalized therapeutic strategies, and unraveling disease pathogenesis. Results: NGS tests were conducted on 548 samples from 522 patients with BC. Ninety-seven point six percentage of tested samples harbored at least one pathogenic alteration. The common alterations included mutations in TP53 (56.2%), PIK3CA (31.2%), GATA3 (13.8%), BRCA2 (10.2%), and amplifications of CCND1 (10.8%), FGF19 (10.0%), and ERBB2 (9.5%). NGS analysis of ERBB2 amplification correlated well with human epidermal growth factor receptor 2 immunohistochemistry and in situ hybridization. RNA panel analyses found potentially actionable and prognostic fusion genes. FCP effectively screened for potentially germline pathogenic/likely pathogenic mutation. Ten point three percent of BC patients received matched therapy guided by NGS, resulting in a significant overall survival advantage (p=0.022), especially for metastatic BCs. Conclusion Clinical NGS provided multifaceted benefits, deepening our understanding of the disease, improving diagnostic precision, and paving the way for targeted therapies. The concrete advantages of FCP highlight the importance of multi-gene testing for BC, especially for metastatic conditions.

Objective: To comprehensively assess the relationship between nerve conduction study (NCS), sympathetic skin response (SSR), and demographic factors in patients with diabetic neuropathy, exploring potential risk factors and mechanisms. Methods: A retrospective study (N=184) included patients diagnosed with type 2 diabetes mellitus undergoing NCS and SSR. Demographic, clinical, and laboratory data were analyzed. Patients were categorized by diabetic peripheral neuropathy (DPN) and SSR stages for comparative analysis. Results: HbA1c levels correlated with DPN progression. SSR stages exhibited age-related differences. Height correlated with DPN but not SSR stages. Body mass index showed no significant differences. Conclusion While DPN progression correlated with glycemic control and duration of diabetes, SSR was influenced by age. Unexpectedly, cholesterol levels remained within the normal range, challenging established concepts. Understanding these relationships is crucial for interpreting test results and developing targeted interventions for diabetic neuropathy.

Tofacitinib, which is used to treat rheumatoid arthritis (RA), is primarily metabolized by the hepatic cytochrome P450 (CYP) enzymes, CYP3A1/2 and CYP2C11. Acetaminophen (APAP), which is frequently used for pain relief in patients with RA, can induce acute liver injury (ALI) when taken in excess, profoundly affecting drug metabolism. Resveratrol (RVT) is a polyphenolic compound with hepatoprotective properties. This study investigated the protective effects of RVT against APAP-induced ALI in rats, and explored its influence on the pharmacokinetics of tofacitinib. In ALI rats, both intravenous and oral administration of tofacitinib resulted in a significant (207% and 181%) increase in the area under the plasma concentration-time curve (AUC), primarily driven by a substantial reduction (66.1%) in non-renal clearance (CLNR) compared to that in control (CON) rats. Notably, RVT administration in ALI rats provided effective liver protection, partially restoring liver function, as evidenced by normalized glutamate oxaloacetate transaminase levels and the pharmacokinetic parameters, AUC and CLNR, closer to those observed in untreated CON rats (117% and 81.9%, respectively). These findings highlight the importance of considering the potential interactions between RVT or polyphenol-rich natural products and medications in patients with ALI in clinical practice.

Purpose: Considering the high disease burden and unique features of Asian patients with breast cancer (BC), it is essential to have a comprehensive view of genetic characteristics in this population. An institutional targeted sequencing platform was developed through the Korea Research-Driven Hospitals project and was incorporated into clinical practice. This study explores the use of targeted next-generation sequencing (NGS) and its outcomes in patients with advanced/metastatic BC in the real world. Materials and Methods: We reviewed the results of NGS tests administered to BC patients using a customized sequencing platform—FiRST Cancer Panel (FCP)—over 7 years. We systematically described clinical translation of FCP for precise diagnostics, personalized therapeutic strategies, and unraveling disease pathogenesis. Results: NGS tests were conducted on 548 samples from 522 patients with BC. Ninety-seven point six percentage of tested samples harbored at least one pathogenic alteration. The common alterations included mutations in TP53 (56.2%), PIK3CA (31.2%), GATA3 (13.8%), BRCA2 (10.2%), and amplifications of CCND1 (10.8%), FGF19 (10.0%), and ERBB2 (9.5%). NGS analysis of ERBB2 amplification correlated well with human epidermal growth factor receptor 2 immunohistochemistry and in situ hybridization. RNA panel analyses found potentially actionable and prognostic fusion genes. FCP effectively screened for potentially germline pathogenic/likely pathogenic mutation. Ten point three percent of BC patients received matched therapy guided by NGS, resulting in a significant overall survival advantage (p=0.022), especially for metastatic BCs. Conclusion Clinical NGS provided multifaceted benefits, deepening our understanding of the disease, improving diagnostic precision, and paving the way for targeted therapies. The concrete advantages of FCP highlight the importance of multi-gene testing for BC, especially for metastatic conditions.

Neuromyelitis optica spectrum disorder (NMOSD) is a rare inflammatory disease that most often affects the optic nerves and spinal cord. We describe a case of 36-year-old woman presented at 13 weeks of gestation with 4 extremities paresthesia and weakness that had lasted for two months at her first visit to our hospital. She had two previous uncomplicated full-term vaginal deliveries and no significant medical or family history. Spine magnetic resonance imaging (MRI) showed extensive cervical cord lesion and aquaporin-4 antibodies were strongly positive, confirming the diagnosis of NMOSD. Initial management with high-dose corticosteroids and plasmapheresis was done and she showed substantial improvement, but she revisited hospital at 26 weeks of gestational age due to visual disturbance and aggravated weakness. Relapse of NMOSD was confirmed by spine MRI, so rituximab therapy was initiated at 28 weeks of gestational age for prevention of recurrence.The patient showed clinical improvement with no adverse effects and relapse of symptoms. She successfully delivered a healthy male infant at 39 weeks and 3 days of gestational age through uncomplicated vaginal delivery. This case demonstrates successful management of new-onset NMOSD during pregnancy using a multi-modal treatment approach including rituximab.