Assessing the Brain Death/Death by Neurologic Criteria Determination Process in Korea: Insights from 10-Year Noncompleted Donation Data.

BACKGROUND: This study aimed to analyze the current status of brain death/death by neurologic criteria (BD/DNC) determination in Korea over a decade, identifying key areas for improvement in the process. METHODS: We conducted a retrospective analysis of data from the Korea Organ Donation Agency spanning 2011 to 2021, focusing on donors whose donations were not completed. The study reviewed demographics, medical settings, diagnoses, and outcomes, with particular emphasis on cases classified as nonbrain death and those resulting in death by cardiac arrest during the BD/DNC assessment. RESULTS: Of the 5047 patients evaluated for potential brain death from 2011 to 2021, 361 were identified as noncompleted donors. The primary reasons for noncompletion included nonbrain death (n = 68, 18.8%), cardiac arrests during the BD/DNC assessment process (n = 80, 22.2%), organ ineligibility (n = 151, 41.8%), and logistical and legal challenges (n = 62, 17.2%). Notably, 25 (36.8%) of them failed to meet the minimum clinical criteria, and 7 of them were potential cases of disagreement between the two clinical examinations. Additionally, most cardiac arrests (n = 44, 55.0%) occurred between the first and second examinations, indicating management challenges in critically ill patients during the assessment period. CONCLUSIONS: Our study highlights significant challenges in the BD/DNC determination process, including the need for improved consistency in neurologic examinations and the management of critically ill patients. The study underscores the importance of refining protocols and training to enhance the accuracy and reliability of brain death assessments, while also ensuring streamlined and effective organ donation practices.

Numerical Study on a Ductile Fracture Model in Pre-Cracked Tension Tests of SUS304L.

The effectiveness of a ductile fracture model in accurately predicting fracture initiation has been demonstrated. In this study, we concentrate on applying the ductile fracture model to pre-cracked structures constructed from SUS304L stainless steel with experimental and numerical analyses. The Swift hardening law was employed to extend the plastic behavior beyond the onset of necking. Additionally, the Hosford-Coulomb model, integrated with a damaged framework, was utilized to predict ductile fracture behavior, particularly under non-proportional loading conditions. Tension tests were conducted on various specimens designed to illustrate various fracture modes resulting from geometric effects. Numerical analyses were conducted to explore the loading histories, utilizing an optimization process to calibrate fracture model parameters. The proposed fracture model is validated against pre-cracked structures detailed in a reference paper. The results convincingly demonstrate that the fracture model effectively predicts both fracture initiation and propagation in pre-cracked structures.

Growth factor-expressing human neural progenitor cell grafts protect motor neurons but do not ameliorate motor performance and survival in ALS mice.

Neural progenitor cells (NPs) have shown several promising benefits for the treatment of neurological disorders. To evaluate the therapeutic potential of human neural progenitor cells (hNPs) in amyotrophic lateral sclerosis (ALS), we transplanted hNPs or growth factor (GF)-expressing hNPs into the central nervous system (CNS) of mutant Cu/Zn superoxide dismutase (SOD1(G93A)) transgenic mice. The hNPs were engineered to express brain-derived neurotrophic factor (BDNF), insulin-like growth factor-1 (IGF-1), VEGF, neurotrophin-3 (NT-3), or glial cell-derived neurotrophic factor (GDNF), respectively, by adenoviral vector and GDNF by lentiviral vector before transplantation. Donor-derived cells engrafted and migrated into the spinal cord or brain of ALS mice and differentiated into neurons, oligodendrocytes, or glutamate transporter-1 (GLT1)-expressing astrocytes while some cells retained immature markers. Transplantation of GDNF- or IGF-1-expressing hNPs attenuated the loss of motor neurons and induced trophic changes in motor neurons of the spinal cord. However, improvement in motor performance and extension of lifespan were not observed in all hNP transplantation groups compared to vehicle-injected controls. Moreover, the lifespan of GDNF-expressing hNP recipient mice by lentiviral vector was shortened compared to controls, which was largely due to the decreased survival times of female animals. These results imply that although implanted hNPs differentiate into GLT1-expressing astrocytes and secrete GFs, which maintain dying motor neurons, inadequate trophic support could be harmful and there is sexual dimorphism in response to GDNF delivery in ALS mice. Therefore, additional therapeutic approaches may be required for full functional recovery.

Phase I Trial of Anti-MET Monoclonal Antibody in MET-Overexpressed Refractory Cancer.

BACKGROUND: Samsung Advance Institute of Technology-301 (SAIT301) is a human immunoglobulin G2 antibody that can specifically target mesenchymal epithelial transition factor (c-MET). This novel antibody has higher priority over hepatocyte growth factors when binding to the Sema domain of c-MET and accelerates the internalization and degradation of c-MET, proving its powerful antitumor activities in intra- as well as extracellular areas. MATERIALS AND METHODS: SAIT301 was administered intravenously once every 3 weeks in c-MET overexpressed solid tumor patients, focusing on metastatic colorectal cancer (CRC) according to common clinical phase I criteria. Dose escalation was performed according to a modified Fibonacci design, following the conventional 3+3 design. The purpose of this phase I study was to assess the safety profile, to establish the recommended dose for clinical phase II studies and to assess potential anticancer activity of the compound. RESULTS: Sixteen patients with a median age of 56 (range, 39-69) years were enrolled in the study. The most common adverse events were decreased appetite (50.0%), hypophosphatemia, fatigue and dizziness (25.0%, respectively), and diarrhea, blood alkaline phosphatase increased and dyspnea (18.8%, respectively). For tumor response, no patients achieved complete response. One (9.1%) CRC patient had a partial response in the 1.23 mg/kg group, 4 (36.4%) patients achieved stable disease (2 in the 0.41 mg/kg group, 2 in the 1.23 mg/kg group, 0 in the 3.69 mg/kg group, and 1 in the 8.61 mg/kg group). Because of the increase in dose-limiting toxicities (DLTs) at 8.61 mg/kg, the 3.69 mg/kg dose was considered the maximum tolerated dose and selected for further assessment in phase II. CONCLUSION: We successfully completed a phase I trial with MET antibody in a MET-overexpressed patient population focusing on CRC, and found that the DLTs were alkaline phosphatase elevation or hypophosphatemia. The recommended dose of SAIT301 for phase II is the dose of 3.69 mg/kg.