INTRODUCTION

Brain death occurs in patients who suffer from severe brain injuries, leading to coma, loss of brainstem reflexes, and apnea. Research indicates that misdiagnosis of brain death often arises from insufficient adherence to established guidelines. This study aims to evaluate and identify any significant variations in physicians' knowledge, attitudes, and practices regarding brain death and organ donation.

This cross-sectional study was conducted among physicians using random sampling. The questionnaire was validated prior to distribution. After obtaining informed consent, participants completed the questionnaire. Data analysis involved the use of frequency and distribution tables, as well as analysis of variance and multivariate analysis of variance.

A total of 113 participants were involved in the study. While years of experience and position influenced knowledge, field of specialization did not show a significant effect. Overall, attitudes remained consistent across different levels of experience and positions. The data revealed a notable lack of training and institutional resources. Although there were some differences in practices, they were not statistically significant.

Significant differences in knowledge were observed based on years of practice. However, no significant differences were found in attitudes and practices, despite variations in responses. Regular seminars and workshops are crucial for staying updated with the latest guidelines. Additionally, it is important to ensure that local guidelines are readily accessible to the broader medical community.

Voluntary contribution has become the only source of donor lungs in China since 2015. To elaborate the outcomes of patients awaiting lung transplantation (LTx) after the implementation of donation after brain death, we performed a retrospective study that encompassed 205 patients with end-stage lung disease who registered for LTx at Shanghai Pulmonary Hospital from January 1, 2015 to January 1, 2021. A total of 180 patients were enrolled in the study. The median waiting time was 1.25 months. Interstitial lung disease (ILD) (103/180, 57.2%) and chronic obstructive pulmonary disease (COPD) (56/180, 31.1%) were the most common diseases in our study population. The mean pulmonary artery pressure (mPAP) of patients in the died-waiting group was higher than that of the survivors (53.29±21.71 mmHg vs. 42.11±18.58 mmHg, P=0.002). The mortality of patients with ILD (34/103, 33.00%) was nearly twice that of patients with COPD (10/56, 17.86%) while awaiting LTx (P=0.041). In the died-waiting group, patients with ILD had a shorter median waiting time than patients with COPD after being listed (0.865 months vs. 4.720 months, P=0.030). ILD as primary disease and mPAP > 35 mmHg were two significant independent risk factors for waitlist mortality, with hazard ratios (HR) of 3.483 (95% CI 1.311-9.111; P=0.011) and 3.500 (95% CI 1.435-8.536; P=0.006). Hence, LTx is more urgently needed in patients with ILD and pulmonary hypertension.
Humans ; Brain Death ; Retrospective Studies ; China ; Lung Transplantation ; Pulmonary Disease, Chronic Obstructive/surgery*

Objective: To describe the actual efficacy of programmed death-1 (PD-1)/ programmed-death ligand 1 (PD-L1) inhibitors in patients with metastatic non-small cell lung cancer (NSCLC) and explore potential prognostic predictive biomarkers. Methods: Patients with metastatic NSCLC who were treated with PD-1/PD-L1 inhibitors at Cancer Hospital, Chinese Academy of Medical Sciences from January 2016 to December 2019, either as monotherapy or in combination with other agents, were consecutively enrolled into this study. We retrospectively collected the data of demographics, clinical information and pathologic assessment to evaluate the therapeutic efficacy and conduct the survival analysis. Major endpoint of our study is progression-free survival (PFS). Secondary endpoints include objective response rate (ORR), disease control rate (DCR) and overall survival (OS). Results: The ORR of 174 patients who underwent PD-1/PD-L1 inhibitor was 28.7%, and the DCR was 79.3%. Immune-related adverse events (irAEs) occurred in 23 patients (13.2%). Brain metastasis, line of treatment, and treatment patterns were associated with the ORR of metastatic NSCLC patients who underwent immunotherapy (P<0.05). After a median follow-up duration of 18.8 months, the median PFS was 10.5 months (ranged from 1.5 to 40.8 months) while the median OS was not reached. The 2-year survival rate was estimated to be 63.0%. The pathologic type was related with the PFS of metastatic NSCLC patients who underwent immunotherapy (P=0.028). Sex, age, brain metastasis and autoimmune diseases were associated with OS (P<0.05). Analysis of the receptor characteristic curve (ROC) of neutrophil/lymphocyte ratio (NLR) predicting ORR of immunotherapy in metastatic NSCLC showed that the areas under the curve of NLR before immunotherapy (NLR(C0)), NLR after one cycle of immunotherapy (NLR(C1)) and ΔNLR were 0.600, 0.706 and 0.628, respectively. Multivariate logistic regression analysis showed that NLR(C1) was an independent factor of the ORR of metastatic NSCLC patients who underwent immunotherapy (OR=0.161, 95% CI: 0.062-0.422), and the efficacy of combination therapy was better than that of single agent (OR=0.395, 95% CI: 0.174-0.896). The immunotherapy efficacy in patients without brain metastasis was better than those with metastasis (OR=0.291, 95% CI: 0.095-0.887). Multivariate Cox regression analysis showed that NLR(C1) was an independent influencing factor of PFS of metastatic NSCLC patients after immunotherapy (HR=0.480, 95% CI: 0.303-0.759). Sex (HR=0.399, 95% CI: 0.161-0.991, P=0.048), age (HR=0.356, 95% CI: 0.170-0.745, P=0.006) were independent influencing factors of OS of metastatic NSCLC patients after immunotherapy. Conclusions: PD-1/PD-L1 inhibitors are proved to be efficacious and have tolerable toxicities for patients with metastatic NSCLC. Patients at advanced age could still benefit from immunotherapy. Brain metastasis is related to compromised response. Earlier application of immunotherapy in combination with other modalities enhances the efficacy without elevating risk of irAEs. NLR(C1) is an early predictor of clinical outcome. The OS of patients younger than 75 years may be improved when treated with immunotherapy.
B7-H1 Antigen/metabolism* ; Brain Neoplasms/drug therapy* ; Carcinoma, Non-Small-Cell Lung/pathology* ; Humans ; Immune Checkpoint Inhibitors ; Lung Neoplasms/pathology* ; Prognosis ; Programmed Cell Death 1 Receptor ; Retrospective Studies

Ischemic stroke caused by intracranial vascular occlusion has become increasingly prevalent with considerable mortality and disability, which gravely burdens the global economy. Current relatively effective clinical treatments are limited to intravenous alteplase and thrombectomy. Even so, patients still benefit little due to the short therapeutic window and the risk of ischemia/reperfusion injury. It is therefore urgent to figure out the neuronal death mechanisms following ischemic stroke in order to develop new neuroprotective strategies. Regarding the pathogenesis, multiple pathological events trigger the activation of cell death pathways. Particular attention should be devoted to excitotoxicity, oxidative stress, and inflammatory responses. Thus, in this article, we first review the principal mechanisms underlying neuronal death mediated by these significant events, such as intrinsic and extrinsic apoptosis, ferroptosis, parthanatos, pyroptosis, necroptosis, and autophagic cell death. Then, we further discuss the possibility of interventions targeting these pathological events and summarize the present pharmacological achievements.
Brain Ischemia/pathology* ; Cell Death ; Humans ; Ischemic Stroke ; Reperfusion Injury/pathology* ; Stroke/pathology* ; Tissue Plasminogen Activator/therapeutic use*

Objective: To explore the outcome of the pediatric-to-adult liver transplantation, including postoperative complications and relevant factors which affecting graft survival. Methods: Data of 55 patients undergoing pediatric-to-adult liver transplantation at the First Affiliated Hospital of Zhejiang University between January 2015 and August 2021 were retrospectively analyzed. The donors consisted of 34 males and 21 females, and the age was (11.8±4.7) years (range: 1 to 17 years). Among the cases,17 cases (30.9%) were donation of brain death,32 cases (58.2%) were donation of cardiac death, and 6 cases (10.9%) were donation after brain death plus cardiac death. The recipients consisted of 32 males and 23 females, and the age was (51.6±10.1) years (range: 27 to 70 years). Among the recipients,10 cases (18.2%) were ABO-incompatible liver transplantation.The influencing factors of early graft survival were analyzed by Student t test,Mann-Whitney U test or χ² test,respectively.Survival curve was drawn by Kaplan-Meier method.Logistic multivariate analysis was used to analyze the independent relevant factors of early postoperative graft loss. Results: Up to October 31,2021,the follow-up time (M(IQR)) was 36.0(43.1)months(range:5.9 to 81.7 months).There were 13 cases with graft loss (two of them underwent re-transplantation due to acute liver failure).The monofactor analysis indicated that cold ischemia time and donor-recipient blood group matching were the relevant factors affecting the early graft survival rate(both P<0.05).Logistic multivariate analysis showed that cold ischemia time and history of recipient gastrointestinal bleeding were independent relevant factors(both P<0.05).Postoperative hepatic artery thrombosis occurred in 3 cases(5.5%), portal vein thrombosis diagnosed in 4 cases(7.3%), portal vein stenosis occurred in 2 cases(3.6%),biliary complications diagnosed in 7 cases(12.7%), and small liver syndrome was found in 8 cases(14.5%). Conclusions: Adult liver transplantation with pediatric donor liver is an effective method to treat end-stage liver disease.Cold ischemia time and history of recipient gastrointestinal bleeding were independent relevant factors for the early graft survival.
Adolescent ; Adult ; Aged ; Blood Group Antigens ; Brain Death ; Child ; Child, Preschool ; Death ; Female ; Gastrointestinal Hemorrhage ; Humans ; Infant ; Liver Transplantation/adverse effects* ; Living Donors ; Male ; Middle Aged ; Retrospective Studies ; Treatment Outcome ; Venous Thrombosis

OBJECTIVES: Urinary tract infection (UTI) is the most common infection complication after kidney transplantation, and the reports of the incidence vary greatly among different centers. This study aims to explore the risk factors for UTI after kidney transplantation with the donation from brain death (DBD) and the impact on graft function, thus to provide theoretical basis for comprehensive prevention and treatment of UTI after kidney transplantation. METHODS: The clinical and laboratory data of DBD kidney transplantation from January 2017 to December 2018 in Xiangya Hospital, Central South University were collected and retrospectively analyzed. Patients were assigned into an UTI group and a non-UTI group. The base line characteristics, post-transplant complications, and graft function were compared between the 2 groups. Multivariate logistic regression was used to analyze the risk factors for UTI. RESULTS: A total of 212 DBD kidney transplant recipients were enrolled in this study. UTI occurred in 44 (20.75%) patients after transplantation. The female, the time of indwelling catheter, and postoperative urinary fistula were independent risk factors for UTI after DBD kidney transplantation. A total of 19 strains of gram-positive bacteria, 12 strains of gram-negative bacteria , and 10 strains of fungi were isolated from the urine of 44 UTI patients. The UTI after kidney transplantation significantly increased time of hospital stay ( CONCLUSIONS UTI after DBD kidney transplantation transplantation affects the renal function at 3 months and increases the patient's economic burden.
Brain Death ; Female ; Humans ; Kidney Transplantation/adverse effects* ; Retrospective Studies ; Risk Factors ; Urinary Tract Infections/etiology*

brain areas of cognition. This region is particularly sensitive to hypoxia and ischemia. Neuregulin-1 (NRG1) has been shown to be able to protect against focal cerebral ischemia. The aim of the present study was to investigate the neuroprotective effect of NRG1 in primary hippocampal neurons and its underlying mechanism. Our data showed oxygen-glucose deprivation (OGD)-induced cytotoxicity and overexpression of ErbB4 in primary hippocampal neurons. Moreover, pretreatment with NRG1 could inhibit OGD-induced overexpression of ErbB4. In addition, NRG1 significantly attenuated neuronal death induced by OGD. The neuroprotective effect of NRG1 was blocked in ischemic neurons after pretreatment with AG1478, an inhibitor of ErbB4, but not after pretreatment with AG879, an inhibitor of ErbB2. These results indicate an important role of ErbB4 in NRG1-mediated neuroprotection, suggesting that endogenous ErbB4 might serve as a valuable therapeutic target for treating global cerebral ischemia.]]>
Anoxia ; Brain ; Brain Ischemia ; Cell Death ; Cognition ; Hippocampus ; Ischemia ; Neuregulin-1 ; Neurons ; Neuroprotection ; Neuroprotective Agents

The complement cascade is a central component of innate immunity which plays a critical role in brain inflammation. Complement C3a receptor (C3aR) is a key mediator of post-ischemic cerebral injury, and pharmacological antagonism of the C3a receptor is neuroprotective in stroke. Cerebral ischemia injures brain endothelial cells, causing blood brain barrier (BBB) disruption which further exacerbates ischemic neuronal injury. In this study, we used an in vitro model of ischemia (oxygen glucose deprivation; OGD) to investigate the protective effect of a C3aR antagonist (C3aRA, SB290157) on brain endothelial cells (bEnd.3). Following 24 hours of reperfusion, OGD-induced cell death was assessed by TUNEL and Caspase-3 staining. Western blot and immunocytochemistry were utilized to demonstrate that OGD upregulates inflammatory, oxidative stress and antioxidant markers (ICAM-1, Cox-2, Nox-2 and MnSOD) in endothelial cells and that C3aRA treatment significantly attenuate these markers. We also found that C3aRA administration restored the expression level of the tight junction protein occludin in endothelial cells following OGD. Interestingly, OGD/reperfusion injury increased the phosphorylation of ERK1/2 and C3aR inhibition significantly reduced the activation of ERK suggesting that endothelial C3aR may act via ERK signaling. Furthermore, exogenous C3a administration stimulates these same inflammatory mechanisms both with and without OGD, and C3aRA suppresses these C3a-mediated responses, supporting an antagonist role for C3aRA. Based on these results, we conclude that C3aRA administration attenuates inflammation, oxidative stress, ERK activation, and protects brain endothelial cells following experimental brain ischemia.
Blood-Brain Barrier ; Blotting, Western ; Brain Ischemia ; Brain ; Caspase 3 ; Cell Death ; Complement C3a ; Complement System Proteins ; Encephalitis ; Endothelial Cells ; Glucose ; Immunity, Innate ; Immunohistochemistry ; In Situ Nick-End Labeling ; In Vitro Techniques ; Inflammation ; Ischemia ; Neurons ; Occludin ; Oxidative Stress ; Phosphorylation ; Reperfusion ; Stroke ; Tight Junctions

Dysregulation of excitatory neurotransmission has been implicated in the pathogenesis of neuropsychiatric disorders. Pharmacological inhibition of N-methyl-D-aspartate (NMDA) receptors is widely used to model neurobehavioral pathologies and underlying mechanisms. There is ample evidence that overstimulation of NMDA-dependent neurotransmission may induce neurobehavioral abnormalities, such as repetitive behaviors and hypersensitization to nociception and cognitive disruption, pharmacological modeling using NMDA has been limited due to the induction of neurotoxicity and blood brain barrier breakdown, especially in young animals. In this study, we examined the effects of intraperitoneal NMDA-administration on nociceptive and repetitive behaviors in ICR mice. Intraperitoneal injection of NMDA induced repetitive grooming and tail biting/licking behaviors in a dose- and age-dependent manner. Nociceptive and repetitive behaviors were more prominent in juvenile mice than adult mice. We did not observe extensive blood brain barrier breakdown or neuronal cell death after peritoneal injection of NMDA, indicating limited neurotoxic effects despite a significant increase in NMDA concentration in the cerebrospinal fluid. These findings suggest that the observed behavioral changes were not mediated by general NMDA toxicity. In the hot plate test, we found that the latency of paw licking and jumping decreased in the NMDA-exposed mice especially in the 75 mg/kg group, suggesting increased nociceptive sensitivity in NMDA-treated animals. Repetitive behaviors and increased pain sensitivity are often comorbid in psychiatric disorders (e.g., autism spectrum disorder). Therefore, the behavioral characteristics of intraperitoneal NMDA-administered mice described herein may be valuable for studying the mechanisms underlying relevant disorders and screening candidate therapeutic molecules.
Adult ; Animals ; Autistic Disorder ; Blood-Brain Barrier ; Cell Death ; Cerebrospinal Fluid ; Grooming ; Humans ; Injections, Intraperitoneal ; Mass Screening ; Mice ; Mice, Inbred ICR ; N-Methylaspartate ; Neurons ; Nociception ; Pathology ; Synaptic Transmission ; Tail

OBJECTIVE: This study aimed to analyze intracranial vessels using brain computed tomography angiography (CTA) and scoring systems to diagnose brain death and predict poor neurologic outcomes of postcardiac arrest patients.METHODS: Initial brain CTA images of postcardiac arrest patients were analyzed using scoring systems to determine a lack of opacification and diagnose brain death. The primary outcome was poor neurologic outcome, which was defined as cerebral performance category score 3 to 5. The frequency, sensitivity, specificity, positive predictive value, negative predictive value, and area under receiver operating characteristic curve for the lack of opacification of each vessel and for each scoring system used to predict poor neurologic outcomes were determined.RESULTS: Patients with poor neurologic outcomes lacked opacification of the intracranial vessels, most commonly in the vein of Galen, both internal cerebral veins, and the mid cerebral artery (M4). The 7-score results (P=0.04) and 10-score results were significantly different (P=0.04) between outcome groups, with an area under receiver operating characteristic of 0.61 (range, 0.48 to 0.72). The lack of opacification of each intracranial vessel and all scoring systems exhibited high specificity (100%) and positive predictive values (100%) for predicting poor neurologic outcomes.CONCLUSION: Lack of opacification of vessels on brain CTA exhibited high specificity for predicting poor neurologic outcomes of patients after cardiac arrest.
Angiography ; Brain Death ; Brain ; Cerebral Arteries ; Cerebral Veins ; Heart Arrest ; Humans ; Hypothermia ; ROC Curve ; Sensitivity and Specificity