Validation of donor fraction cell-free DNA with biopsy-proven cardiac allograft rejection in children and adults

ObjectivesDonor-specific cell-free DNA shows promise as a noninvasive marker for allograft rejection, but as yet has not been validated in both adult and pediatric recipients. The study objective was to validate donor fraction cell-free DNA as a noninvasive test to assess for risk of acute cellular rejection and antibody-mediated rejection after heart transplantation in pediatric and adult recipients.MethodsPediatric and adult heart transplant recipients were enrolled from 7 participating sites and followed for 12 months or more with plasma samples collected immediately before all endomyocardial biopsies. Donor fraction cell-free DNA was extracted, and quantitative genotyping was performed. Blinded donor fraction cell-free DNA and clinical data were analyzed and compared with a previously determined threshold of 0.14%. Sensitivity, specificity, negative predictive value, positive predictive value, and receiver operating characteristic curves were calculated.ResultsA total of 987 samples from 144 subjects were collected. After applying predefined clinical and technical exclusions, 745 samples from 130 subjects produced 54 rejection samples associated with the composite outcome of acute cellular rejection grade 2R or greater and pathologic antibody-mediated rejection 2 or greater and 323 healthy samples. For all participants, donor fraction cell-free DNA at a threshold of 0.14% had a sensitivity of 67%, a specificity of 79%, a positive predictive value of 34%, and a negative predictive value of 94% with an area under the curve of 0.78 for detecting rejection. When analyzed independently, these results held true for both pediatric and adult cohorts at the same threshold of 0.14% (negative predictive value 92% and 95%, respectively).ConclusionsDonor fraction cell-free DNA at a threshold of 0.14% can be used to assess for risk of rejection after heart transplantation in both pediatric and adult patients with excellent negative predictive value.     

Implementation of molecular matching in transplantation requires further characterization of both immunogenicity and antigenicity of individual HLA epitopes

Over the past decade, high HLA epitope mismatch scores have been associated with inferior transplant outcomes using several tools, of which HLAMatchmaker is most well-known. This software uses theoretically defined polymorphic amino acid configurations, called eplets, for HLA compatibility analysis. Although consideration of eplet mismatch loads has potential for immunological risk stratification of transplant patients, the use of eplet matching in organ allocation algorithms is hindered by lacking knowledge of the immunogenicity of individual eplets, and the possibility that single mismatched amino acids, rather than complete eplets, are responsible for HLA antibody induction.There are several approaches to define eplet immunogenicity, such as antibody verification of individual eplets, and data-driven approaches using large datasets that correlate specific eplet mismatches to donor specific antibody formation or inferior transplant outcomes. Data-driven approaches can also be used to define whether single amino acid mismatches may be more informative than eplet mismatches for predicting HLA antibody induction.When using epitope knowledge for the assignment of unacceptable antigens, it important to realize that alleles sharing an eplet to which antibodies have formed are not automatically all unacceptable since multiple contact sites determine the binding strength and thus biological function and pathogenicity of an antibody, which may differ between reactive alleles.While the future looks bright for using HLA epitopes in clinical decision making, major steps need to be taken to make this a clinical reality.     

Pump Speed Optimization in Patients Implanted With the HeartMate 3 Device

Background

Pump speed optimization in patients implanted with a ventricular assist device represents a major challenge during the follow-up period. We present our findings on whether combined invasive hemodynamic ramp tests and cardiopulmonary exercise testing (CPX) can help optimize patient management.

肺移植患者姑息照护的研究进展

肺移植是终末期肺病的有效治疗方法。该文介绍了肺移植患者姑息照护的概念、必要性、开展情况、影响肺移植患者姑息照护的障碍因素、促进肺移植患者姑息照护的策略、姑息照护对肺移植患者的效果等方面，为国内肺移植患者姑息照护的发展提供借鉴，从而提高肺移植患者的生活质量。     

Update on pediatric corneal diseases and keratoplasty

Managing pediatric corneal disorders is challenging as the prognosis of pediatric keratoplasty depends on several factors. Advancements in the genetic basis of congenital corneal diseases and investigations in congenital corneal conditions provide a better understanding of pediatric corneal conditions. Surgeons performing keratoplasty in children now have a choice of various techniques. Evolving surgical techniques of anterior lamellar and endothelial keratoplasties have expanded the management interventions in these pediatric corneal morbidity conditions; however, considerable concerns still exist in association with corneal transplantation in infants and children. Outcomes in pediatric keratoplasty depend upon the preoperative indications, the timing of surgical intervention, intraoperative and postoperative factors including the patient/care givers’ compliance. Factors such as low scleral rigidity, higher rate of graft failure, need for frequent examinations under anesthesia, and difficulty in optimal visual acuity assessment still remain a considerable challenge in pediatric scenarios. In children, deprivation amblyopia as a result of the corneal opacification can adversely affect visual development, causing dense amblyopia. Outcomes to surgical interventions for management of corneal opacification in children are further compromised by the preexisting amblyopia apart from the concerns of refractive outcome of the graft. Graft rejection, graft infection, amblyopia, and glaucoma continue to be serious concerns. In recent years both anterior and posterior lamellar keratoplasty techniques are being increasingly performed in pediatric eyes, which offer advantages in the form of lower risk of graft rejection. The timing of surgery, careful case selection, cautious intraoperative approach, and optimal postoperative management can improve the anatomical and functional outcome in difficult cases.     

异基因造血干细胞移植患者生活质量变化轨迹及影响因素研究

目的 探讨异基因造血干细胞移植患者3年内的生活质量变化轨迹及影响因素。方法 采用便利抽样法,选取2016年7月—2017年10月于苏州市某三级甲等医院行异基因造血干细胞移植的患者作为调查对象,在患者移植前（入仓前1~2 d）、移植后1个月、3个月、半年、1年、1年半及3年时采用一般资料调查表及癌症治疗功能评价-骨髓移植测评量表进行调查。 结果 异基因造血干细胞移植患者的癌症治疗功能评价-骨髓移植测评量表总分在移植后1个月时降至最低,此后呈逐渐上升趋势,半年时基本恢复至移植前水平,3年时总分显著高于移植前,差异具有统计学意义（P<0.05）。生理健康、功能健全及干细胞移植3个维度得分与癌症治疗功能评价-骨髓移植测评量表总分变化轨迹一致,呈波动上升型;情绪稳定维度在移植前得分最低,随移植时间延长逐渐上升;社交/家庭健全维度移植前得分与移植后各时间点得分比较,差异无统计学意义（P>0.05）。多元线性回归分析结果显示,影响患者移植后3年时生活质量的主要因素为居住地（t=3.175,P=0.002）、家庭人均月收入（t=3.320,P=0.001）、移植相关并发症（t=-6.955,P<0.001）及患者是否回归工作/学习（t=2.706,P=0.008）。 结论 异基因造血干细胞移植患者总体生活质量呈波动上升趋势,癌症治疗功能评价-骨髓移植测评量表5个维度间的恢复时间及变化轨迹存在差异。至移植后3年时,居住地为农村、家庭人均月收入较低、患有移植相关并发症及尚未回归工作/学习的患者生活质量更差。护理人员可根据患者生活质量变化轨迹动态调整护理措施,为其提供更为精准的延续性护理。     

Mesenchymal stromal cell secretome in liver failure: Perspectives on COVID-19 infection treatment

Due to their immunomodulatory potential and release of trophic factors that promote healing, mesenchymal stromal cells (MSCs) are considered important players in tissue homeostasis and regeneration. MSCs have been widely used in clinical trials to treat multiple conditions associated with inflammation and tissue damage. Recent evidence suggests that most of the MSC therapeutic effects are derived from their secretome, including the extracellular vesicles, representing a promising approach in regenerative medicine application to treat organ failure as a result of inflammation/fibrosis. The recent outbreak of respiratory syndrome coronavirus, caused by the newly identified agent severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has forced scientists worldwide to use all available instruments to fight the infection, including the inflammatory cascade caused by this pandemic disease. The use of MSCs is a valid approach to combat organ inflammation in different compartments. In addition to the lungs, which are considered the main inflammatory target for this virus, other organs are compromised by the infection. In particular, the liver is involved in the inflammatory response to SARS-CoV-2 infection, which causes organ failure, leading to death in coronavirus disease 2019 (COVID-19) patients. We herein summarize the current implications derived from the use of MSCs and their soluble derivatives in COVID-19 treatment, and emphasize the potential of MSC-based therapy in this clinical setting.