Objective: Thoracic pedicle screw fixation is technically demanding because of the natural variability in pedicle anatomy, a challenge that is further exacerbated in patients with spinal tumors who often have compromised pedicles. The L-point entry, juxtapedicular, and endplate-parallel trajectory (L-JET) technique was developed to provide a uniform entry point, a predictable screw trajectory, and the capacity to accommodate larger-diameter screws at levels T3–10. This study aimed to evaluate the safety and feasibility of the L-JET technique in comparison with the conventional transpedicular method. Methods: A comparative analysis of consecutively collected data was performed to evaluate outcomes associated with the L-JET technique in patients undergoing surgery for thoracic extradural spinal tumors. The L-point was defined as the intersection of a vertical line along the lateral margin of the facet joint and a horizontal line along the upper edge of the transverse process. The screw trajectory was planned with 30° of medial convergence in the axial plane, creating a juxtapedicular path, and a straightforward trajectory in the sagittal plane. Primary outcome measures included screw diameter, screw length, cortical breach rate, and the need for revision surgery, as assessed using computed tomography scans and medical records. Results: A total of 108 screws were placed in 22 patients using the L-JET technique, while 98 screws were placed in 18 patients using the conventional technique. The L-JET group used significantly larger-diameter screws (6.06±0.65 mm) than the conventional group (5.74±0.80 mm, p=0.02), with no significant difference observed in screw length between groups. Medial cortical breach occurred in one screw in each group, and no supra- or infrapedicular breaches were identified. No screw-related neurovascular complications or revision surgeries occurred in either group. Conclusion The L-JET technique enables consistent screw placement with larger-diameter screws, even in compromised pedicles associated with thoracic spinal tumors, without increasing the risk of complications or the need for revision surgery.

Background and Objectives: In chronic heart failure (HF), natriuretic peptide (NP) levels are higher in atrial fibrillation (AF) compared to sinus rhythm (SR). However, due to the loss of atrial contraction, AF patients are prone to hemodynamic decompensation at earlier stages.Since NP levels reflect disease severity, acutely decompensated AF patients may exhibit lower NP levels compared to SR patients, who retain greater hemodynamic reserve. Methods: We analyzed 5,048 patients with acute HF from the Korea Acute Heart Failure registry with available NP data. NP levels and echocardiographic parameters were compared between AF and SR patients. The association of NP levels with in-hospital and one-year mortality was also assessed according to cardiac rhythm. Results: Brain natriuretic peptide (BNP) and N-terminal pro-B-type natriuretic peptide (NT-proBNP) were measured in 2,027 and 3,021 patients, respectively. NP levels were lower in AF than in SR (median BNP, 740 vs. 1,044 pg/mL; median NT-proBNP, 4,420 vs. 5,198 pg/mL), particularly in HF with reduced or mildly reduced ejection fraction. A similar trend was observed regardless of HF onset or etiology. AF patients had smaller left ventricular (LV) end-diastolic diameter and larger left atrial size compared to SR patients. Higher NP tertiles were associated with increased in-hospital and one-year mortality in both groups. Conclusions In acute HF, NP levels are lower in AF than in SR. AF patients also exhibited smaller LV chamber sizes. Nevertheless, NP levels remain strong predictors of outcomes in both AF and SR patients.

Objective: Because of the possible therapeutic benefit of removing occult tumor cells, a source of recurrence and chemoresistance, total parietal peritonectomy (TPP) is an alternative treatment for advanced epithelial ovarian/fallopian tube/primary peritoneal cancer. Interventional studies comparing TPP with selective parietal peritonectomy (SPP) are in progress. Since surgeons skilled in TPP are essential for such trials to be conducted, this nationwide survey aimed to examine current peritonectomy practice among gynecologic oncologists in Korea. Methods: A 17-item questionnaire, developed by a surgery committee and reviewed by the scientific review board of the Korean Gynecology Oncology Group (KGOG), was distributed to 144 KGOG members. The questionnaire was divided into 3 categories: respondent demographics, peritonectomy practice during primary debulking surgery (PDS), and peritonectomy practice during interval debulking surgery (IDS). Results: We received 88 (61.1%) valid responses. Of the valid respondents, 98.9% and 93.8% performed SPP during PDS and IDS, respectively. Only 4.9% of the respondents performed TPP during IDS. Most respondents performed peritonectomy in cases where optimal postoperative outcomes were expected. Approximately 50.6% of the respondents had performed peritonectomy independently, while the others did so in cooperation with non-gynecologic surgeons. The primary reasons for not performing TPP were concerns about morbidity and uncertainty about the clinical benefits of the procedure. Conclusion SPP is the predominant technique used in both PDS and IDS in Korea. A small percentage (4.9%) of gynecologic oncologists have performed TPP during IDS. Accordingly, a study regarding the feasibility of TPP should be conducted before proceeding with a prospective clinical trial.

We previously reported that leukotriene B4 (LTB4) contained in Trichomonas vaginalis-derived secretory products (TvSP) play an essential role in interleukin-8 (IL-8) production in human mast cell line (HMC-1 cells) via LTB4 receptor (BLT)-mediated Nuclear Factor-kappa B (NF-кB) activation. Dynamin, a GTPase, has been known to be involved in endocytosis of receptors for signaling of production of cytokine or chemokines. In the present study, we investigated the role of dynamin-mediated BLT1 endocytosis in TvSP-induced IL-8 production. When HMC-1 cells were transfected with BLT1 or BLT2 siRNA, TvSP-induced IL-8 production was significantly inhibited compared with that in cells transfected with control siRNA. In addition, pretreatment of HMC-1 cells with a dynamin inhibitor (Dynasore) reduced IL-8 production induced by TvSP or LTB4. TvSP- or LTB4- induced phosphorylation of NF-кB was also attenuated by pretreatment with Dynasore. After exposing HMC-1 cells to TvSP or LTB4, BLT1 was translocated from the intracellular compartments to the plasma membrane within 30 min. At 60 min after stimulation with TvSP or LTB4, BLT1 remigrated from the cell surface to intracellular areas. Pretreatment of HMC-1 cells with dynamin-2 siRNA blocked internalization of BLT1 induced by TvSP or LTB4. Co-immunoprecipitation experiments revealed that dynamin-2 strongly interacted with BLT1 60 min after stimulation with TvSP or LTB4. These results suggest that T. vaginalis-secreted LTB4 induces IL-8 production in HMC-1 cells via dynamin 2-mediated endocytosis of BLT1 and phosphorylation of NF-кB.

Trichomoniasis is caused by a sexually transmitted flagellate protozoan parasite Trichomonas vaginalis. T. vaginalis-derived secretory products (TvSP) contain lipid mediators such as leukotriene B4 (LTB4) and various cysteinyl leukotrienes (CysLTs) which included LTC4, LTD4, and LTE4. However, the signaling mechanisms by which T. vaginalis-induced CysLTs stimulate interleukin (IL)-8 production in human mast cells remain unclear. In this study, we investigated these mechanisms in human mast cells (HMC-1). Stimulation with TvSP resulted in increased intracellular reactive oxygen species (ROS) generation and NADPH oxidase 2 (NOX2) activation compared to unstimulated cells. Pre-treatment with NOX2 inhibitors such as diphenyleneiodonium chloride (DPI) or apocynin significantly reduced ROS production in TvSP-stimulated HMC-1 cells. Additionally, TvSP stimulation increased NOX2 protein expression and the translocation of p47phox from the cytosol to the membrane. Pretreatment of HMC-1 cells with PI3K or PKC inhibitors reduced TvSP-induced p47phox translocation and ROS generation. Furthermore, NOX2 inhibitors or NOX2 siRNA prevented CREB phosphorylation and IL-8 gene expression or protein secretion induced by TvSP. Pretreatment with a CysLTR antagonist significantly inhibited TvSP-induced ROS production, CREB phosphorylation, and IL-8 production. These results indicate that CysLT-mediated activation of NOX2 plays a crucial role in ROS-dependent IL-8 production in human mast cells stimulated by T. vaginalis-secreted CysLTs. These findings enhance our understanding of the inflammatory response in trichomoniasis and may inform the development of targeted therapies to mitigate this response.

Paxlovid is the first approved oral treatment for coronavirus disease 2019 and includes nirmatrelvir, a protease inhibitor targeting the main protease (Mpro ) of SARS-CoV-2, as one of the key components. While some specific mutations emerged in Mpro were revealed to significantly reduce viral susceptibility to nirmatrelvir in vitro, there is no report regarding resistance to nirmatrelvir in patients and animal models for SARS-CoV-2 infection yet. We recently developed xenograft tumors derived from Calu-3 cells in immunodeficient mice and demonstrated extended replication of SARS-CoV-2 in the tumors. In this study, we investigated the effect of nirmatrelvir administration on SARS-CoV-2 replication. Treatment with nirmatrelvir after virus infection significantly reduced the replication of the parental SARS-CoV-2 and SARS-CoV-2 Omicron at 5 days post-infection (dpi). However, the virus titers were completely recovered at the time points of 15 and 30 dpi. The virus genomes in the tumors at 30 dpi were analyzed to investigate whether nirmatrelvir-resistant mutant viruses had emerged during the extended replication of SARS-CoV-2. Various mutations in several genes including ORF1ab, ORF3a, ORF7a, ORF7b, ORF8, and N occurred in the SARS-CoV-2 genome; however, no mutations were induced in the Mpro sequence by a single round of nirmatrelvir treatment, and none were observed even after two rounds of treatment. The parental SARS-CoV-2 and its sublineage isolates showed similar IC50 values of nirmatrelvir in Vero E6 cells. Therefore, it is probable that inducing viral resistance to nirmatrelvir in vivo is challenging differently from in vitro passage.

Omphalitis is an infection of the umbilicus that can cause inflammation to spread. Omphalitis is rare in adults; however, it can occasionally occur owing to urachal remnants. A 61-year-old male patient with abdominal pain and umbilical pus was admitted to the emergency room.Abdominal computed tomography revealed peritonitis with multiple intra-abdominal abscesses.The patient was diagnosed with peritonitis resulting from urachal cyst rupture. Laparoscopic drainage of the abscesses and excising of the umbilicus and intra-abdominal fistula tract were performed. Antibiotics were administered, and the patient was discharged uneventfully. The rarity of peritonitis caused by infection and urachal cyst rupture can make diagnosing omphalitis challenging. Therefore, in this case report and literature review, we discuss the diagnosis and treatment of complicated omphalitis, which rarely progresses to peritonitis owing to ruptured urachal cysts.

Breast cancer is the most common cancer and a frequent cause of cancer-related deaths among women wordlwide. As therapeutic strategies for breast cancer have limitations, novel chemotherapeutic reagents and treatment strategies are needed. In this study, we investigated the anti-cancer effect of synthetic homoisoflavane derivatives of cremastranone on breast cancer cells. Homoisoflavane derivatives, SH-17059 and SH-19021, reduced cell proliferation through G2/M cell cycle arrest and induced caspase-independent cell death. These compounds increased heme oxygenase-1 (HO-1) and 5-aminolevulinic acid synthase 1 (ALAS1), suggesting downregulation of heme. They also induced reactive oxygen species (ROS) generation and lipid peroxidation. Furthermore, they reduced expression of glutathione peroxidase 4 (GPX4). Therefore, we suggest that the SH-17059 and SH-19021 induced the caspase-independent cell death through the accumulation of iron from heme degradation, and the ferroptosis might be one of the potential candidates for caspase-independent cell death.

Background/Aims: The optimal systolic blood pressure (SBP) goal for elderly patients with hypertension, especially to reduce cardiovascular disease (CVD) incidence and improve outcome, is unclear. This study aimed to evaluate the beneficial effects of intensive treatment for hypertension on the incidence of CVD in elderly Korean patients. Methods: The HOW to Optimize eLDerly systolic Blood Pressure (HOWOLD-BP) trial is a multicenter, parallel-design, open-label, randomized controlled trial designed to evaluate whether intensive treatment (SBP ≤ 130 mmHg) will provide more benefits in lowering the incidence and mortality associated with CVD than standard treatment (SBP ≤ 140 mmHg) in elderly patients with hypertension aged ≥ 65 years. For this study, eleven university hospitals in Korea will enroll approximately 3,176 elderly patients with hypertension between 2019 and 2022. Patients will be requested to visit the clinic every 4 months for the first year and every 6 months thereafter for 36 months. Parameters, including clinic and home blood pressure, anthropometric and laboratory findings, and frailty assessments, will be collected according to the standardized protocol. The primary outcome is a composite of CVD (acute coronary syndrome, stroke, and heart failure) incidence and cardiovascular deaths. Results: As of December 2021, 1,655 participants had been enrolled in the study, including 831 patients in the standard group and 824 patients in the intensive group. Conclusions The HOWOLD-BP trial is the first study performed in Korea to evaluate the beneficial effects of intensive blood pressure treatment on CVD in elderly patients with hypertension. The results of this study will help clarify the appropriate target SBP for this population.

Background: It has been known that the fear of contagion during the coronavirus disease 2019 (COVID-19) creates time delays with subsequent impact on mortality in patients with acute myocardial infarction (AMI). However, difference of time delay and clinical outcome in patients with ST-segment elevation myocardial infarction (STEMI) or non-STEMI between the COVID-19 pandemic and pre-pandemic era has not been fully investigated yet in Korea. The aim of this study was to investigate the impact of COVID-19 pandemic on time delays and clinical outcome in patients with STEMI or non-STEMI compared to the same period years prior. Methods: A total of 598 patients with STEMI (n = 195) or non-STEMI (n = 403) who underwent coronary angiography during the COVID-19 pandemic (February 1 to April 30, 2020) and prepandemic era (February 1 to April 30, 2017, 2018, and 2019) were analyzed in this study. Main outcomes were the incidence of time delay, cardiac arrest, and in-hospital death. Results: There was 13.5% reduction in the number of patients hospitalized with AMI during the pandemic compared to pre-pandemic era. In patients with STEMI, door to balloon time tended to be longer during the pandemic compared to pre-pandemic era (55.7 ± 12.6 minutes vs. 60.8 ± 13.0 minutes, P = 0.08). There were no significant differences in cardiac arrest (15.6% vs. 10.4%, P = 0.397) and in-hospital mortality (15.6% vs. 10.4%, P = 0.397) between pre-pandemic and the pandemic era. In patients with non-STEMI, symptom to door time was significantly longer (310.0 ± 346.2 minutes vs. 511.5 ± 635.7 minutes, P = 0.038) and the incidence of cardiac arrest (0.9% vs. 3.5%, P = 0.017) and in-hospital mortality (0.3% vs.2.3%, P = 0.045) was significantly greater during the pandemic compared to pre-pandemic era. Among medications, angiotensin converting enzyme inhibitors/angiotensin type 2 receptor blockers (ACE-I/ARBs) were underused in STEMI (64.6% vs. 45.8%, P = 0.021) and non-STEMI (67.8% vs. 57.0%, P = 0.061) during the pandemic. Conclusion During the COVID-19 pandemic, there has been a considerable reduction in hospital admissions for AMI, time delay, and underuse of ACE-I/ARBs for the management of AMI, and this might be closely associated with the excess death in Korea.