BACKGROUND: Embryo-endometrium cross-talk is one of the critical processes for implantation, and unsuccessful cross-talk leads to infertility. We established an endometrium-embryo (or embryoid bodies, hEBs) in vitro model in 2D and 3D conditions and assessed its potential through the fusion of embryos and the expression of specific markers. METHODS: C57BL/6 mouse embryos and human embryoid body (hEB) derived from embryonic stem cells were prepared as embryo models. Mouse endometrium (EM) and human endometrium cell line, HEC-1-A, were prepared, and 2D or 3D EMs were generated. The viability of the 3D endometrium was analyzed, and the optimal ratio of the gelation was revealed. The invasion of the embryos or hEBs was examined by immunostaining and 3D image rendering. RESULTS: The embryos and the alternative hEBs were effectively fused into 2D or 3D vitro EM models in both mouse and human models. The fused embryos and hEBs exhibited migration and further development. Notably, the established in vitro model expressed Oct4 and E-Cadherin, markers for early embryonic development; human CG Receptor and Progesterone Receptor, critical for implantation and pregnancy maintenance; and TSH Receptor, Epiregulin, and Prolactin, indicators of endometrial receptivity and embryo implantation. CONCLUSION This study marks a significant advancement in the field, as we have successfully established a novel in vitro model for studying embryo-endometrium cross-talk. This model, a crucial tool for understanding fertility and the causes of miscarriage due to failed implantation, provides a unique platform for investigating the complex processes of successful implantation and pregnancy, underscoring its potential impact on reproductive health.

Background: Respiratory infections play a major role in acute exacerbation of chronic obstructive pulmonary disease (AECOPD). This study assessed the prevalence of bacterial and viral pathogens and their clinical impact on patients with AECOPD. Methods: This retrospective study included 1,186 patients diagnosed with AECOPD at 28 hospitals in South Korea between 2015 and 2018. We evaluated the identification rates of pathogens, basic patient characteristics, clinical features, and the factors associated with infections by potentially drug-resistant (PDR) pathogens using various microbiological tests. Results: Bacteria, viruses, and both were detected in 262 (22.1%), 265 (22.5%), and 129 (10.9%) of patients, respectively. The most common pathogens included Pseudomonas aeruginosa (17.8%), Mycoplasma pneumoniae (11.2%), Streptococcus pneumoniae (9.0%), influenza A virus (19.0%), rhinovirus (15.8%), and respiratory syncytial virus (6.4%). Notably, a history of pulmonary tuberculosis (odds ratio [OR], 1.66; p=0.046), bronchiectasis (OR, 1.99; p=0.032), and the use of a triple inhaler regimen within the past 6 months (OR, 2.04; p=0.005) were identified as significant factors associated with infection by PDR pathogens. Moreover, patients infected with PDR pathogens exhibited extended hospital stays (15.9 days vs. 12.4 days, p=0.018) and higher intensive care unit admission rates (15.9% vs. 9.5%, p=0.030). Conclusion This study demonstrates that a variety of pathogens are involved in episodes of AECOPD. Nevertheless, additional research is required to confirm their role in the onset and progression of AECOPD.

Background and Objectives: Outcomes of deferring percutaneous coronary intervention (PCI) without invasive physiologic assessment for intermediate coronary lesions is uncertain.We sought to compare long-term outcomes between medical treatment and PCI of intermediate lesions without invasive physiologic assessment. Methods: A total of 899 patients with intermediate coronary lesions between 50% and 70% diameter-stenosis were randomized to the conservative group (n=449) or the aggressive group (n=450). For intermediate lesions, PCI was performed in the aggressive group, but was deferred in the conservative group. The primary endpoint was major adverse cardiac events (MACE, a composite of all-cause death, myocardial infarction [MI], or ischemia-driven any revascularization) at 3 years. Results: The number of treated lesions per patient was 0.8±0.9 in the conservative group and 1.7±0.9 in the aggressive group (p=0.001). At 3 years, the conservative group had a significantly higher incidence of MACE than the aggressive group (13.8% vs. 9.3%; hazard ratio [HR], 1.49; 95% confidence interval [CI], 1.00–2.21; p=0.049), mainly driven by revascularization of target intermediate lesion (6.5% vs. 1.1%; HR, 5.69; 95% CI, 2.20–14.73;p<0.001). Between 1 and 3 years after the index procedure, compared to the aggressive group, the conservative group had significantly higher incidence of cardiac death or MI (3.2% vs.0.7%; HR, 4.34; 95% CI, 1.24–15.22; p=0.022) and ischemia-driven any revascularization. Conclusions For intermediate lesions, medical therapy alone, guided only by angiography, was associated with a higher risk of MACE at 3 years compared with performing PCI, mainly due to increased revascularization.

Background: The 5th edition of WHO classification (WHO5) renamed pituitary adenoma as pituitary neuroendocrine tumor (PitNET), aligning with NET nomenclature from other sites.This study investigated the clinicopathological characteristics of surgically resected PitNET based on the WHO5 classification. Methods: A retrospective analysis was conducted on 210 cases of surgically resected and pathologically confirmed PitNET treated at Seoul National University Hospital from 2021 to 2023. The tumors were graded using the French five-tiered grading system proposed by Trouillas et al. Detailed information on grade 3 metastatic PitNET cases is provided. Results: The cohort’s median age was 53 years (age range: 8–84 years), with a male-to-female ratio of 1:1.1. Mean tumor size was 2.5 cm (range: 0.1–6.5 cm). Macroadenomas predominated (91.9%), followed by microadenoma (6.7%), and giant tumors (1.4%), with 56.2% extending suprasellarly. SF1-lineage PitNET was most prevalent (49.5%), followed by PIT1-lineage (23.3%) and TPIT-lineage (17.1%). Null cell tumors (5.7%) and unclassified plurihormonal PitNET (4.3%) were rare. PIT1-lineage PitNET comprised somatotrophs (47.0%), mature plurihormonal PIT1 lineage tumors (18.4%), thyrotrophs (16.3%), immature PIT1-lineage tumors (16.3%), and acidophilic stem cell tumors (n=1), however, there was no lactotroph PitNET. Among SF1-lineage tumors, serologically non-functional tumors predominated (79%), while, immunohistochemically, 71.2% were gonadotrophin (FSH/LH)-positive.Tumor grades by the French five-tiered classification system were distributed as follows:grade 1a (58.1%), 1b (17.6%), 2a (16.2%), 2b (7.1%), and 3 (1.0%). Two cases of metastatic corticotroph PitNET were observed: The first case, a 50-year-old female had liver metastasis and experienced tumor recurrence 7 years after his initial diagnosis of PitNET, ultimately dying 9.5 years later. The primary tumor appeared bland, but the metastatic tumor exhibited a high mitotic rate and a Ki-67 index was 48%. The second case involved a 44-year-old man with metastases to the paranasal sinus, liver, and bone. Despite showing initial bland histopathology and a low proliferation index, this tumor displayed aggressive behavior.The patient had a recurrence 1.5 years after diagnosis, with additional metastases emerging 3 years later. He survived for 8.0 years and is currently disease-free following surgery, chemotherapy, and radiotherapy. Conclusion This comprehensive analysis of surgically resected PitNETs using the new WHO5 classification provides valuable insights into the distribution of the subtypes in the surgical cohort. Key findings were the predominant gonadotroph PitNET, the absence of lactotroph PitNET, and the rarity of null cell tumors in surgical cases. The lack of lactotrophs was mainly due to medical treatment. This study highlights the discrepancy between serological and immunohistochemical findings of SF1-lineage PitNETs. While metastatic PitNET cases showed poor prognosis, the predictive value of the French grading system for PitNET requires further validation through extended follow-up.

Background: The 5th edition of WHO classification (WHO5) renamed pituitary adenoma as pituitary neuroendocrine tumor (PitNET), aligning with NET nomenclature from other sites.This study investigated the clinicopathological characteristics of surgically resected PitNET based on the WHO5 classification. Methods: A retrospective analysis was conducted on 210 cases of surgically resected and pathologically confirmed PitNET treated at Seoul National University Hospital from 2021 to 2023. The tumors were graded using the French five-tiered grading system proposed by Trouillas et al. Detailed information on grade 3 metastatic PitNET cases is provided. Results: The cohort’s median age was 53 years (age range: 8–84 years), with a male-to-female ratio of 1:1.1. Mean tumor size was 2.5 cm (range: 0.1–6.5 cm). Macroadenomas predominated (91.9%), followed by microadenoma (6.7%), and giant tumors (1.4%), with 56.2% extending suprasellarly. SF1-lineage PitNET was most prevalent (49.5%), followed by PIT1-lineage (23.3%) and TPIT-lineage (17.1%). Null cell tumors (5.7%) and unclassified plurihormonal PitNET (4.3%) were rare. PIT1-lineage PitNET comprised somatotrophs (47.0%), mature plurihormonal PIT1 lineage tumors (18.4%), thyrotrophs (16.3%), immature PIT1-lineage tumors (16.3%), and acidophilic stem cell tumors (n=1), however, there was no lactotroph PitNET. Among SF1-lineage tumors, serologically non-functional tumors predominated (79%), while, immunohistochemically, 71.2% were gonadotrophin (FSH/LH)-positive.Tumor grades by the French five-tiered classification system were distributed as follows:grade 1a (58.1%), 1b (17.6%), 2a (16.2%), 2b (7.1%), and 3 (1.0%). Two cases of metastatic corticotroph PitNET were observed: The first case, a 50-year-old female had liver metastasis and experienced tumor recurrence 7 years after his initial diagnosis of PitNET, ultimately dying 9.5 years later. The primary tumor appeared bland, but the metastatic tumor exhibited a high mitotic rate and a Ki-67 index was 48%. The second case involved a 44-year-old man with metastases to the paranasal sinus, liver, and bone. Despite showing initial bland histopathology and a low proliferation index, this tumor displayed aggressive behavior.The patient had a recurrence 1.5 years after diagnosis, with additional metastases emerging 3 years later. He survived for 8.0 years and is currently disease-free following surgery, chemotherapy, and radiotherapy. Conclusion This comprehensive analysis of surgically resected PitNETs using the new WHO5 classification provides valuable insights into the distribution of the subtypes in the surgical cohort. Key findings were the predominant gonadotroph PitNET, the absence of lactotroph PitNET, and the rarity of null cell tumors in surgical cases. The lack of lactotrophs was mainly due to medical treatment. This study highlights the discrepancy between serological and immunohistochemical findings of SF1-lineage PitNETs. While metastatic PitNET cases showed poor prognosis, the predictive value of the French grading system for PitNET requires further validation through extended follow-up.

Background and Objectives: Outcomes of deferring percutaneous coronary intervention (PCI) without invasive physiologic assessment for intermediate coronary lesions is uncertain.We sought to compare long-term outcomes between medical treatment and PCI of intermediate lesions without invasive physiologic assessment. Methods: A total of 899 patients with intermediate coronary lesions between 50% and 70% diameter-stenosis were randomized to the conservative group (n=449) or the aggressive group (n=450). For intermediate lesions, PCI was performed in the aggressive group, but was deferred in the conservative group. The primary endpoint was major adverse cardiac events (MACE, a composite of all-cause death, myocardial infarction [MI], or ischemia-driven any revascularization) at 3 years. Results: The number of treated lesions per patient was 0.8±0.9 in the conservative group and 1.7±0.9 in the aggressive group (p=0.001). At 3 years, the conservative group had a significantly higher incidence of MACE than the aggressive group (13.8% vs. 9.3%; hazard ratio [HR], 1.49; 95% confidence interval [CI], 1.00–2.21; p=0.049), mainly driven by revascularization of target intermediate lesion (6.5% vs. 1.1%; HR, 5.69; 95% CI, 2.20–14.73;p<0.001). Between 1 and 3 years after the index procedure, compared to the aggressive group, the conservative group had significantly higher incidence of cardiac death or MI (3.2% vs.0.7%; HR, 4.34; 95% CI, 1.24–15.22; p=0.022) and ischemia-driven any revascularization. Conclusions For intermediate lesions, medical therapy alone, guided only by angiography, was associated with a higher risk of MACE at 3 years compared with performing PCI, mainly due to increased revascularization.

BACKGROUND: Embryo-endometrium cross-talk is one of the critical processes for implantation, and unsuccessful cross-talk leads to infertility. We established an endometrium-embryo (or embryoid bodies, hEBs) in vitro model in 2D and 3D conditions and assessed its potential through the fusion of embryos and the expression of specific markers. METHODS: C57BL/6 mouse embryos and human embryoid body (hEB) derived from embryonic stem cells were prepared as embryo models. Mouse endometrium (EM) and human endometrium cell line, HEC-1-A, were prepared, and 2D or 3D EMs were generated. The viability of the 3D endometrium was analyzed, and the optimal ratio of the gelation was revealed. The invasion of the embryos or hEBs was examined by immunostaining and 3D image rendering. RESULTS: The embryos and the alternative hEBs were effectively fused into 2D or 3D vitro EM models in both mouse and human models. The fused embryos and hEBs exhibited migration and further development. Notably, the established in vitro model expressed Oct4 and E-Cadherin, markers for early embryonic development; human CG Receptor and Progesterone Receptor, critical for implantation and pregnancy maintenance; and TSH Receptor, Epiregulin, and Prolactin, indicators of endometrial receptivity and embryo implantation. CONCLUSION This study marks a significant advancement in the field, as we have successfully established a novel in vitro model for studying embryo-endometrium cross-talk. This model, a crucial tool for understanding fertility and the causes of miscarriage due to failed implantation, provides a unique platform for investigating the complex processes of successful implantation and pregnancy, underscoring its potential impact on reproductive health.

Background: Respiratory infections play a major role in acute exacerbation of chronic obstructive pulmonary disease (AECOPD). This study assessed the prevalence of bacterial and viral pathogens and their clinical impact on patients with AECOPD. Methods: This retrospective study included 1,186 patients diagnosed with AECOPD at 28 hospitals in South Korea between 2015 and 2018. We evaluated the identification rates of pathogens, basic patient characteristics, clinical features, and the factors associated with infections by potentially drug-resistant (PDR) pathogens using various microbiological tests. Results: Bacteria, viruses, and both were detected in 262 (22.1%), 265 (22.5%), and 129 (10.9%) of patients, respectively. The most common pathogens included Pseudomonas aeruginosa (17.8%), Mycoplasma pneumoniae (11.2%), Streptococcus pneumoniae (9.0%), influenza A virus (19.0%), rhinovirus (15.8%), and respiratory syncytial virus (6.4%). Notably, a history of pulmonary tuberculosis (odds ratio [OR], 1.66; p=0.046), bronchiectasis (OR, 1.99; p=0.032), and the use of a triple inhaler regimen within the past 6 months (OR, 2.04; p=0.005) were identified as significant factors associated with infection by PDR pathogens. Moreover, patients infected with PDR pathogens exhibited extended hospital stays (15.9 days vs. 12.4 days, p=0.018) and higher intensive care unit admission rates (15.9% vs. 9.5%, p=0.030). Conclusion This study demonstrates that a variety of pathogens are involved in episodes of AECOPD. Nevertheless, additional research is required to confirm their role in the onset and progression of AECOPD.