Objective: 68 Ga-NGUL is a novel prostate-specific membrane antigen (PSMA)-targeting tracer based on Glu-Urea-Lys derivatives conjugated to a 1,4,7-triazacyclononane-N,N’,N’’-triacetic acid (NOTA) chelator via a thiourea-type short linker. This phase I clinical trial of 68 Ga-NGUL was conducted to evaluate the safety and radiation dosimetry of 68 Ga-NGUL in healthy volunteers and the lesion detection rate of 68 Ga-NGUL in patients with prostate cancer. Materials and Methods: We designed a prospective, open-label, single-arm clinical trial with two cohorts comprising six healthy adult men and six patients with metastatic prostate cancer. Safety and blood test-based toxicities were monitored throughout the study. PET/CT scans were acquired at multiple time points after administering 68 Ga-NGUL (2 MBq/kg; 96–165 MBq). In healthy adults, absorbed organ doses and effective doses were calculated using the OLINDA/EXM software. In patients with prostate cancer, the rates of detecting suspicious lesions by 68 Ga-NGUL PET/CT and conventional imaging (CT and bone scintigraphy) during the screening period, within one month after recruitment, were compared. Results: All 12 participants (six healthy adults aged 31–32 years and six prostate cancer patients aged 57–81 years) completed the clinical trial. No drug-related adverse events were observed. In the healthy adult group, 68 Ga-NGUL was rapidly distributed, with the highest uptake in the kidneys. The median effective dose coefficient was calculated as 0.025 mSv/MBq, and cumulative activity in the bladder had the highest contribution. In patients with metastatic prostate cancer, 229 suspicious lesions were detected using either 68 Ga-NGUL PET/CT or conventional imaging. Among them, 68 Ga-NGUL PET/CT detected 199 (86.9%) lesions and CT or bone scintigraphy detected 114 (49.8%) lesions. Conclusion 68 Ga-NGUL can be safely applied clinically and has shown a higher detection rate for the localization of metastatic lesions in prostate cancer than conventional imaging. Therefore, 68 Ga-NGUL is a valuable option for prostate cancer imaging.

Purpose: The aim of this study was to investigate the efficacy of various epidermal growth factor receptor (EGFR)–tyrosine kinase inhibitors (TKIs) plus bevacizumab in advanced EGFR-mutant lung adenocarcinoma patients. Materials and Methods: From August 2016 to October 2020, we enrolled advanced lung adenocarcinoma patients harboring exon 19 deletion or L858R receiving gefitinib, erlotinib and afatinib plus bevacizumab as the first-line treatment for the purposes of analysis. Results: A total of 36 patients were included in the final analysis. Three patients received gefitinib, 17 received erlotinib, and 16 received afatinib combined with bevacizumab as the first-line treatment. The objective response rate was 77.8%, and disease control rate was 94.4%. The overall median progression-free survival (PFS) was 16.4 months, while the median PFS was 17.1 months in patients with exon 19 deletion, and 16.2 months in patients with L858R mutation (p=0.311). Regarding the use of different EGFR-TKIs, the median PFS was 17.1 months in the erlotinib group and 21.6 months in the afatinib group (p=0.617). In patients with brain metastasis at baseline, the median PFS was 18.9 months in the erlotinib group and 16.4 months in the afatinib group (p=0.747). Amongst patients harboring exon 19 deletion, the median PFS was 16.2 months in the erlotinib group and not-reached in the afatinib group (p=0.141). In patients with L858R mutation, the median PFS was 18.9 months in the erlotinib group and 16.2 months in the afatinib group (p=0.481). Conclusion Our research demonstrates that not only erlotinib combined with bevacizumab, but also afatinib plus bevacizumab as first-line treatment, provides solid clinical efficacy in advanced EGFR-mutant lung adenocarcinoma patients.

PURPOSE: The main objective of this study was to investigate the relationship among the clinical characteristics and the frequency of T790M mutation in advanced epidermal growth factor receptor (EGFR)–mutant lung adenocarcinoma patients with acquired resistance after firstline EGFR–tyrosine kinase inhibitor (TKI) treatment. MATERIALS AND METHODS: We enrolled EGFR-mutant stage IIIB-IV lung adenocarcinoma patients, who had progressed to prior EGFR-TKI therapy, and evaluated their rebiopsy EGFR mutation status. RESULTS: A total of 205 patients were enrolled for analysis. The overall T790M mutation rate of rebiopsy was 46.3%. The T790M mutation rates among patients with exon 19 deletion mutation, exon 21 L858R point mutation, and other mutations were 55.0%, 37.3%, and 27.3%, respectively. Baseline exon 19 deletion was associated with a significantly higher frequency of T790M mutation (adjusted odds ratio, 2.14; 95% confidence interval [CI], 1.20 to 3.83; p=0.010). In the exon 19 deletion subgroup, there was a greater prevalence of T790M mutation than other exon 19 deletion subtypes in patients with the Del E746-A750 mutation (61.6% vs. 40.6%; odds ratio, 2.35; 95% CI, 1.01 to 5.49; p=0.049). The progression-free survival (PFS) of first-line TKI treatment > 11 months was also associated with a higher T790M mutation rate (54.1% vs. 39.3%; adjusted odds ratio, 1.82; 95% CI, 1.02 to 3.25; p=0.044). Patients who underwent rebiopsy at metastatic sites had more chance to harbor T790M mutation (52.6% vs. 33.8%; adjusted odds ratio, 1.97; 95% CI, 1.06 to 3.67; p=0.032). CONCLUSION: PFS of first-line EGFR-TKI, rebiopsy site, EGFR exon 19 deletion and its subtype Del E746-A750 mutation are associated with the frequency of T790M mutation.
Adenocarcinoma* ; Disease-Free Survival ; Epidermal Growth Factor* ; Exons ; Humans ; Lung Neoplasms ; Lung* ; Mutation Rate ; Odds Ratio ; Phosphotransferases ; Point Mutation ; Prevalence ; Receptor, Epidermal Growth Factor* ; Sequence Deletion

PURPOSE: Epidermal growth factor receptor (EGFR) T790M mutation serves as an important predictor of osimertinib efficacy. However, little is known about how it works among patients with various timings of T790M emergence and treatment. MATERIALS AND METHODS: Advanced EGFR-mutant lung adenocarcinoma patients with positive T790M mutation in tumor were retrospectively enrolled and observed to determine the outcomes of osimertinib treatment. We evaluated the association between patients’ characteristics and the efficacy of osimertinib treatment, particularly with respect to the timing of T790M emergence and osimertinib prescription. RESULTS: A total of 91 patients were enrolled, including 14 (15.4%) with primary and 77 (84.6%) with acquired T790M mutation. The objective response rate and disease controlratewere 60.9% and 85.1%, respectively. The median progression-free survival (PFS) and overall survival were 11.5 months (95% confidence interval [CI], 9.0 to 14.0) and 30.4 months (95% CI, 11.3 to 49.5), respectively. There was no significant difference in response rate and PFS between primary and acquired T790M populations. In the acquired T790M subgroup, patientswho received osimertinib after T790M had been confirmed by rebiopsy had a longer PFS than those with intercalated treatments between rebiopsy and osimertinib prescription (14.0 months [95% CI, 9.0 to 18.9] vs. 7.2 months [95% CI, 3.7 to 10.8]; adjusted hazard ratio, 0.48 [95% CI, 0.24 to 0.98; p=0.043]). Rebiopsy timing did not influence the outcome. CONCLUSION: Osimertinib prescription with intercalated treatment following rebiopsy but not the timing of T790M emergence influenced the treatment outcome. We suggest that it is better to start osimertinib treatment once T790M mutation has been confirmed by biopsy.
Adenocarcinoma ; Biopsy ; Disease-Free Survival* ; Humans ; Lung ; Prescriptions ; Receptor, Epidermal Growth Factor ; Retrospective Studies ; Treatment Outcome

The pneumonia severity index (PSI) and CURB-65 are widely used tools for the prediction of community-acquired pneumonia (CAP). This study was conducted to evaluate validation of severity scoring system including the PSI and CURB-65 scores of Korean CAP patients. In the prospective CAP cohort (participated in by 14 hospitals in Korea from January 2009 to September 2011), 883 patients aged over 18 yr were studied. The 30-day mortalities of all patients were calculated with their PSI index classes and CURB scores. The overall mortality rate was 4.5% (40/883). The mortality rates per CURB-65 score were as follows: score 0, 2.3% (6/260); score 1, 4.0% (12/300); score 2, 6.0% (13/216); score 3, 5.7% (5/88); score 4, 23.5% (4/17); and score 5, 0% (0/2). Mortality rate with PSI risk class were as follows: I, 2.3% (4/174); II, 2.7% (5/182); III, 2.3% (5/213); IV, 4.5% (11/245); and V, 21.7% (15/69). The subgroup mortality rate of Korean CAP patients varies based on the severity scores and CURB-65 is more valid for the lower scores, and PSI, for the higher scores. Thus, these variations must be considered when using PSI and CURB-65 for CAP in Korean patients.
Adolescent ; Adult ; Aged ; Aged, 80 and over ; Asian Continental Ancestry Group ; Cohort Studies ; Community-Acquired Infections/*mortality ; Female ; Humans ; Intensive Care Units ; Male ; Middle Aged ; Pneumonia/*mortality ; Prospective Studies ; Republic of Korea ; *Severity of Illness Index ; Young Adult

Sinus pericranii is a rare vascular anomaly that's characterized by an extracranial vascular mass with anastomotic connections between the intracranial and extracranial systems via the diploic veins of the skull. Preoperative evaluations for making the diagnosis are important to help prevent unexpected intraoperative bleeding. We report here on a case of surgically treated sinus pericranii in a 20-year-old female following minor head trauma. The clinical manifestations, pathogenesis and managements are discussed, and we also review the relevant literature.
Craniocerebral Trauma ; Female ; Hemorrhage ; Humans ; Sinus Pericranii ; Skull ; Veins ; Young Adult

Vertebrobasilar junction entrapment due to a clivus fracture is a rare clinical observation. The present case report describes a 54-yr-old man who sustained a major craniofacial injury. The patient displayed a stuporous mental state (Glasgow Coma Scale [GCS]=8) and left hemiparesis (Grade 3). The initial computed tomography (CT) scan revealed a right subdural hemorrhage in the frontotemporal region, with a midline shift and longitudinal clival fracture. A decompressive craniectomy with removal of the hematoma was performed. Two days after surgery, a follow-up CT scan showed cerebellar and brain stem infarction, and a CT angiogram revealed occlusion of the left vertebral artery and entrapment of vertebrobasilar junction by the clival fracture. A decompressive suboccipital craniectomy was performed and the patient gradually recovered. This appears to be a rare case of traumatic vertebrobasilar junction entrapment due to a longitudinal clival fracture, including a cerebellar infarction caused by a left vertebral artery occlusion. A literature review is provided.
Basilar Artery/*injuries ; Humans ; Male ; Middle Aged ; Skull Fractures/*complications/radiography ; Tomography, X-Ray Computed ; Vertebral Artery/*injuries

Kaempferol is the major flavonol in green tea and exhibits many biomedically useful properties such as antioxidative, cytoprotective and anti-apoptotic activities. To elucidate its effects on the skin, we investigated the transcriptional profiles of kaempferol-treated HaCaT cells using cDNA microarray analysis and identified 147 transcripts that exhibited significant changes in expression. Of these, 18 were up-regulated and 129 were down-regulated. These transcripts were then classified into 12 categories according to their functional roles: cell adhesion/cytoskeleton, cell cycle, redox homeostasis, immune/defense responses, metabolism, protein biosynthesis/modification, intracellular transport, RNA processing, DNA modification/ replication, regulation of transcription, signal transduction and transport. We then analyzed the promoter sequences of differentially-regulated genes and identified over-represented regulatory sites and candidate transcription factors (TFs) for gene regulation by kaempferol. These included c-REL, SAP-1, Ahr-ARNT, Nrf-2, Elk-1, SPI-B, NF-kappaB and p65. In addition, we validated the microarray results and promoter analyses using conventional methods such as real-time PCR and ELISA-based transcription factor assay. Our microarray analysis has provided useful information for determining the genetic regulatory network affected by kaempferol, and this approach will be useful for elucidating gene-phytochemical interactions.
Base Sequence ; Cell Line ; DNA Primers ; Enzyme-Linked Immunosorbent Assay ; *Gene Expression Profiling ; Gene Expression Regulation/*drug effects ; Humans ; Kaempferols/*pharmacology ; Keratinocytes/*drug effects/metabolism ; Oligonucleotide Array Sequence Analysis ; Promoter Regions, Genetic ; Reverse Transcriptase Polymerase Chain Reaction ; Transcription Factors/*physiology ; Transcription, Genetic/*drug effects

OBJECTIVE: This study was designed to evaluate the feasibility and clinical implications of CT angiography (CTA) in patients with acute ischemic stroke. METHODS: From August 2004 to July 2005, 24 cases of acute ischemic stroke were prospectively included in this study. We checked location of ischemic parenchymal lesion, location of vascular occlusion, degree of collateral supply, and presence of other accompanying vascular lesions on CT and CTA, and assessed the usefulness of CTA by comparing the findings with those of diffusionweighted MR imaging and digital subtraction angiography. RESULTS: Average time required for performing CT and CTA and getting reconstructed images was 30 minutes. Location of the parenchymal lesions and the corresponding occluded or stenosed artery could be clarified in 16 cases (67%) and 20 cases (83%), respectively. There were 13 cases of severe stenosis and 7 cases of occlusion. In 7 cases of major arterial occlusion, degree of collateral circulation could be assessed as good in 5, and moderate in 2. Incidental unruptured intracranial aneurysms were identified in 5 cases. CONCLUSION: CTA could provide valuable information regarding locations of parenchymal lesion and vascular occlusion, degree of collateral supply, and presence of accompanying intracranial aneurysm in cases of acute ischemic stroke without significant time delay, thereby guiding therapeutic plan.
Angiography* ; Angiography, Digital Subtraction ; Arteries ; Collateral Circulation ; Constriction, Pathologic ; Humans ; Intracranial Aneurysm ; Magnetic Resonance Imaging ; Prospective Studies ; Stroke*

BACKGROUND: Thoracic actinomycosis is a relatively uncommon anaerobic infection caused by Actinomyces israelii. There have been only a few case reports of endobronchial actinomycosis. The aim of this study was to evaluate the clinical manifestation and treatment of endobronchial actinomycosis. MATERIAL AND METHODS: Seven patients with endobronchial actinomycosis, who were diagnosed in the past 10 years, were retrospectively reviewed. RESULTS: Cough and sputum were the most common symptoms. The chest radiograph and computed tomography showed necrotic consolidation (n=3), atelectasis (n=2), mass (n=1) and an endobronchial nodule (n=1). Proximal broncholithiasis was observed in five patients. All cases were initially suspected to have either lung cancer or tuberculosis. In these patients, the median duration of intravenous antibiotics was 3 days (range 0-12 days) and the median duration of oral antibiotics was 147 days (range 20-412 days). Two patients received oral antibiotic therapy only. There was no clinical evidence of a recurrence. CONCLUSION: Endobronchial actinomycosis frequently manifests as a proximal obstructive calcified endobronchial nodule that is associated with distal post-obstructive pneumonia. The possibility of endobronchial actinomycosis is suggested when findings of broncholithiasis are present at chest CT. The traditional recommendation of 2-6 weeks of intravenous antibiotics and 6-12 months of oral antibiotic therapy are not necessarily essential in all cases of endobronchial actinomycosis.
Actinomyces ; Actinomycosis* ; Anti-Bacterial Agents ; Bronchoscopy ; Cough ; Diagnosis* ; Humans ; Lung Neoplasms ; Pneumonia ; Pulmonary Atelectasis ; Radiography, Thoracic ; Recurrence ; Retrospective Studies ; Sputum ; Tomography, X-Ray Computed ; Tuberculosis