大脑皮质发育不良大鼠脑皮质和海马中的NeuN和GFAP表达研究

目的：探讨大脑皮质发育不良（DCD）大鼠大脑半球、海马的免疫组化病理学特点及其所致难治性癫痫（IE）的发生机制。方法：建立X-射线照射诱导的皮质下异位结节大鼠DCD模型,采用SP免疫组织化学方法检测神经元特异核蛋白抗原（NeuN）和星形胶质细胞特异抗原（GFAP）在大鼠脑皮质下和海马中异位结节的表达,阳性细胞计数,用SPSS10．0软件统计。结果：DCD组与正常对照或母鼠组白质比较,皮质下异位结节内NeuN免疫阳性神经元和GFAP免疫阳性细胞数密度分别增加30倍和16倍,差异有统计学意义（P〈0．05）。同龄而不同部位DCD病变组间脑皮质Ⅰ～Ⅲ层异位结节、皮质下异位结节和CA1区异位结节中NeuN、GFAP免疫阳性细胞数密度或阳性平均光密度值比较,差异无统计学意义。结论：DCD鼠脑NeuN及GFAP的分布证实了皮质下异位结节的内在属性,异位结节是灰质,主要是由神经元和星形胶质细胞构成。     

Comparison of in situ preservation techniques for kidneys from donors after circulatory death: a systematic review and meta-analysis

BackgroundSeveral techniques have been developed to reduce the warm ischaemic injury of donation after circulatory death (DCD) organs before procurement. There are scarce data about the in situ preservation techniques for kidney graft outcomes. The aim of this systematic review was to evaluate the best in situ preservation method for kidney graft outcomes from organs obtained from controlled and uncontrolled DCD.MethodsA systematic review of the PubMed (MEDLINE), Embase, LILACS and Cochrane databases was conducted. Studies that compare two or more in situ preservation techniques were identified and included. Only studies which provided enough data to calculate odds ratio were eligible for meta-analysis. PROSPERO registration: CRD42020179598.ResultsThe search strategy yielded 7,121 studies. Ultimately, 14 retrospective studies were included. Because of heterogeneity, the included studies provided weak evidence that normothermic regional perfusion (NRP) is the best in situ preservation technique in terms of delayed graft function (DGF) rates. Regarding primary nonfunction (PNF), we carried out a meta-analysis of 10 studies with a pooled OR of 0.83 (95% CI: 0.40–1.71), for the NRP. In regard to DGF, pooled OR for NRP was 0.36 (95% CI: 0.25–0.54).ConclusionsNRP in the DCD donor could improve kidney graft function and be considered the in situ preservation technique of choice for abdominal organs.     

Urinary metabolites predict prolonged duration of delayed graft function in DCD kidney transplant recipients

Extending kidney donor criteria, including donation after circulatory death (DCD), has resulted in increased rates of delayed graft function (DGF) and primary nonfunction. Here, we used Nuclear Magnetic Resonance (NMR) spectroscopy to analyze the urinary metabolome of DCD transplant recipients at multiple time points (days 10, 42, 180, and 360 after transplantation). The aim was to identify markers that predict prolonged duration of functional DGF (fDGF). Forty‐seven metabolites were quantified and their levels were evaluated in relation to fDGF. Samples obtained at day 10 had a different profile than samples obtained at the other time points. Furthermore, at day 10 there was a statistically significant increase in eight metabolites and a decrease in six metabolites in the group with fDGF (N = 53) vis‐à‐vis the group without fDGF (N = 22). In those with prolonged fDGF (≥21 days) (N = 17) urine lactate was significantly higher and pyroglutamate lower than in those with limited fDGF (<21 days) (N = 36). In order to further distinguish prolonged fDGF from limited fDGF, the ratios of all metabolites were analyzed. In a logistic regression analysis, the sum of branched‐chain amino acids (BCAAs) over pyroglutamate and lactate over fumarate, predicted prolonged fDGF with an AUC of 0.85. In conclusion, kidney transplant recipients with fDGF can be identified based on their altered urinary metabolome. Furthermore, two ratios of urinary metabolites, lactate/fumarate and BCAAs/pyroglutamate, adequately predict prolonged duration of fDGF.     

Barriers to live and deceased kidney donation by patients with chronic neurological diseases: Implications for donor selection,donation timing,logistics, and regulatory compliance

Live and deceased kidney donation by the numerous patients with advanced, progressive systemic neurological diseases, and other chronic neurological conditions (eg, high C‐spine injury) remains largely unexplored. In a review of our current clinical practice, we identified multiple regulatory and clinical barriers. For live donation, mandatory reporting of postdonation donor deaths within 2 years constitutes a strong programmatic disincentive. We propose that the United Network for Organ Sharing should provide explicit regulatory guidance and reassurance for programs wishing to offer live donation to patients at higher risk of death during the reporting period. Under the proposal, live donor deaths within 30 days would still be regarded as donation‐related, but later deaths would be related to the underlying disease. For deceased donation, donation after circulatory death (DCD) immediately following self‐directed withdrawal of life‐sustaining treatment (“conscious DCD”) is not universally covered by existing DCD agreements with donor hospitals. Organ procurement organizations should thus systematically strive to revise these agreements. Obtaining adequate first‐person consent from these communicatively severely impaired patients may be challenging. Optimized preservation and allocation protocols may maximize utilization of these DCD kidneys. Robust public debate and action by all stakeholders is necessary to lower existing barriers and maximize donation opportunities for patients with chronic neurological conditions.     

Donor prone positioning protects lungs from injury during warm ischemia

A large proportion of controlled donation after circulatory death (cDCD) donor lungs are declined because cardiac arrest does not occur within a suitable time after the withdrawal of life‐sustaining therapy. Improved strategies to preserve lungs after asystole may allow the recovery team to arrive after death actually occurs and enable the recovery of lungs from more cDCD donors. The aim of this study was to determine the effect of donor positioning on the quality of lung preservation after cardiac arrest in a cDCD model. Cardiac arrest was induced by withdrawal of ventilation under anesthesia in pigs. After asystole, animals were divided into 2 groups based on body positioning (supine or prone). All animals were subjected to 3 hours of warm ischemia. After the observation period, donor lungs were explanted and preserved at 4°C for 6 hours, followed by 6 hours of physiologic and biological lung assessment under normothermic ex vivo lung perfusion. Donor lungs from the prone group displayed significantly greater quality as reflected by better function during ex vivo lung perfusion, less edema formation, less cell death, and decreased inflammation compared with the supine group. A simple maneuver of donor prone positioning after cardiac arrest significantly improves lung graft preservation and function.     

Feasibility and safety of using low-body-weight donors in pediatric liver transplantation

BackgroundDonors with low-body-weight were previously reported to be related to inferior recipient outcomes in pediatric liver transplantation. However, the scarce availability of age and size-matched organs has encouraged us to re-evaluate the feasibility and safety of using low-body-weight donors.MethodsWe retrospectively analyzed 91 deceased donor pediatric liver transplantation between January 2014 and December 2016, donor weight less than 5 kg was defined as low-body-weight donors. The recipients were divided into two groups according to donor weight.(≤ 5 kg and 5 kg < to ≤ 20 kg). Donor and recipient characteristics, perioperative data, postoperative complications as well as graft and recipient survival rate were comparedResultsThe recipients and grafts recovery after transplantation were comparable between two groups. The recipients receiving low-body-weight donors showed higher risk of hepatic artery thrombosis and small-for-size syndrome, however, these complications can effectively be treated by our strategies. The 2-year patient survival rates were 92.9% and 95.2%, 2-year graft survival rates were 92.9% and 93.7% in Groups 1 and 2, without significant difference.ConclusionsOur finding suggested that the utility of livers from low-body-weight donors is a potential strategy to increase donor availability in well-selected pediatric recipients.Level of EvidenceIII     

Temporal variability in continuous versus discontinuous drawing for children with Developmental Coordination Disorder

Children with Developmental Coordination Disorder (DCD) are reported to have high temporal variability in tasks requiring precise timing. The current study examined whether this timing deficit was due to the cerebellar 'explicit timing' process in the discontinuous, but not the continuous movement. Ten children with DCD and 31 typically developing children performed continuous, discontinuous circle and line drawing tasks. Results showed that both children with DCD and their age-matched controls had higher temporal variability in the discontinuous than that in the continuous movements. Individual comparisons between each child with DCD and the performance of typically developing children revealed that 2 out of 10 children with DCD showed limited timing deficit in both types of discontinuous drawing (lines and circles). Additionally, three different children with DCD had timing problems with only discontinuous line drawing. Thus, the possibility of a compromised cerebellar function may exist in a subgroup of children with DCD. This work raises a critical issue with respect to the functional heterogeneity of this population and emphasizes the importance of an individualized analysis in this movement disorder.