Not Dying Alone — Modern Compassionate Care in the Covid-19 Pandemic

http://deepblue.lib.umich.edu/bitstream/2027.42/156077/1/nejmp2007781.pdfSEL

Frailty Is Associated With Increased Rates of Acute Cellular Rejection Within 3 Months After Liver Transplantation

Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/154606/1/lt25690.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/154606/2/lt25690_am.pd

Nodular regenerative hyperplasia and liver transplantation: a systematic review

Nodular regenerative hyperplasia (NRH) is a primary disease of the liver that may cause noncirrhotic portal hypertension. Common causes include autoimmune, hematologic, immune deficiency, and myeloproliferative disorders. Given the limited data regarding the development of NRH in contemporary immunosuppressive protocols and the occurrence of NRH post-liver transplantation, we systematically reviewed NRH as it pertains to liver transplantation. We performed a comprehensive search for NRH and transplantation. Nineteen studies were identified with relevant data for NRH as an indication for a liver transplant. Thirteen studies were identified with relevant data pertaining to NRH development after liver transplant. Pooled analysis revealed 0.9% of liver transplant recipients had NRH. A total of 113 patients identified with NRH underwent liver transplantation. Most series report transplants done after the failure of endoscopic banding and TIPS management of portal hypertension. Reported 5-year graft and patient survival ranged from 73%–78% and 73%–90%. The pooled incidence of NRH after liver transplant for all indications was 2.9% and caused complications of portal hypertension. Complications related to portal hypertension secondary to NRH are a rare indication for a liver transplant. NRH can develop at any time after liver transplantation often without an identifiable cause, which may lead to portal hypertension requiring treatment or even re-transplantation

The impact of intraoperative fluid management during laparoscopic donor nephrectomy on donor and recipient outcomes

BackgroundIntraoperative fluid management during laparoscopic donor nephrectomy (LDN) may have a significant effect on donor and recipient outcomes. We sought to quantify variability in fluid management and investigate its impact on donor and recipient outcomes.MethodsA retrospective review of patients who underwent LDN from July 2011 to January 2016 with paired kidney recipients at a single center was performed. Patients were divided into tertiles of intraoperative fluid management (standard, high, and aggressive). Donor and recipient demographics, intraoperative data, and postoperative outcomes were analyzed.ResultsOverall, 413 paired kidney donors and recipients were identified. Intraoperative fluid management (mL/h) was highly variable with no correlation to donor weight (kg) (R = 0.017). The aggressive fluid management group had significantly lower recipient creatinine levels on postoperative day 1. However, no significant differences were noted in creatinine levels out to 6 months between groups. No significant differences were noted in recipient postoperative complications, graft loss, and death. There was a significant increase (P < 0.01) in the number of total donor complications in the aggressive fluid management group.ConclusionsAggressive fluid management during LDN does not improve recipient outcomes and may worsen donor outcomes compared to standard fluid management.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/149691/1/ctr13542_am.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/149691/2/ctr13542.pd

Early Transfusion with Mesenchymal Stem Cell Derived Extracellular Vesicles: A New Transfusion Strategy for Life-Threatening Hemorrhage and Traumatic Brain Injury

Background: Life-threatening hemorrhage and traumatic brain injury (TBI) have a significantly increasing global burden and remain leading causes of preventable deaths. Effective interventions may protect the brain against ongoing damage and improve the long-term outcomes. A growing area of interest is transfusion of cell-based therapies, particularly with bone marrow-derived mesenchymal stem cells (MSC). Transfusion using MSC derived extracellular vesicles (EVs) have shown to improve neurologic outcomes in animal models of life-threatening hemorrhage, stroke, and TBI. However, the precise mechanisms remain poorly characterized. In the present study, we aimed to elucidate some of the key cerebral genes, pathways, and networks that were modulated after transfusion of EVs in a porcine model of hemorrhagic shock (HS) and TBI. Methods: Swine were subjected to HS (40% blood volume) and severe TBI (8-mm cortical impact). After 1 hour of shock, animals were randomized (n=4/group) to treatment with either lactated Ringer\u27s (LR) or LR+EV. Both groups received fluid resuscitation after 2 hours of shock, and autologous packed red blood cells 5 hours later. After 7-days, brains were harvested and RNA-sequencing was performed. The transcriptomic data was imported into the iPathway pipeline for bioinformatics analyses. Results: 5,273 genes were differentially expressed in the LR+EV group vs. LR alone (total 9,588 measured genes, Figure 1). Table 1 lists the top 10 genes exhibiting the greatest up- and down-expression based on fold change. Genes with the greatest up-regulation were involved in synaptic transmission and neuronal development and differentiation, while down-regulated genes were involved in inflammation. Gene Ontology terms experiencing the greatest modulation were involved in inflammation, brain development, and cell adhesion. Pathway analysis revealed significant modulation in the glutamatergic and GABAergic systems. Network analysis revealed down-regulation of inflammation (Figure 2), and up-regulation of neurogenesis, and neuron survival and differentiation. Conclusions: In a porcine model of HS+TBI, EV transfusion was associated with an attenuation of cerebral inflammatory networks and a promotion of neurogenesis and neuroplasticity. These transcriptomic changes could explain the observed neuroprotective and neurorestorative properties associated with EV transfusion. EV transfusion reduces the hyper-inflammatory response and may have great promise in improving outcomes in concurrent life-threatening hemorrhage and severe TBI. Further testing of this novel strategy and its implications in transfusion medicine are warranted

Early Treatment With A Single Dose of Mesenchymal Stem Cell Derived Extracellular Vesicles Modulates The Brain Transcriptome to Create Neuroprotective Changes In A Porcine Model of Traumatic Brain Injury and Hemorrhagic Shock

BACKGROUND: Cell-based therapies using mesenchymal stem cell derived extracellular vesicles (EVs) improve neurologic outcomes in animal models of traumatic brain injury (TBI), stroke, and hemorrhage. Using a porcine 7-day survival model of TBI and hemorrhagic shock (HS), we previously demonstrated that EV-treatment was associated with reduced brain lesion size, neurologic severity score, and cerebral inflammation. However, the underlying cellular and genomic mechanisms remain poorly defined. We hypothesize that EV treatment modulates the brain transcriptome to enhance neuroprotection and neurorestoration following TBI + HS. METHODS: Swine were subjected to severe TBI (8-mm cortical impact) and HS (40% blood volume). After 1 hour of shock, animals were randomized (n=4/group) to treatment with either lactated Ringer\u27s (LR) or LR + EV. Both groups received fluid resuscitation after 2 hours of shock, and autologous packed red blood cells 5 hours later.After 7-days, brains were harvested and RNA-sequencing was performed. The transcriptomic data was imported into the iPathway pipeline for bioinformatics analyses. RESULTS: 5,273 genes were differentially expressed in the LR + EV group vs. LR alone (total 9,588 measured genes). Genes with the greatest upregulation were involved in synaptic transmission and neuronal development and differentiation, while downregulated genes were involved in inflammation. GO-terms experiencing the greatest modulation were involved in inflammation, brain development, and cell adhesion. Pathway analysis revealed significant modulation in the glutamatergic and GABAergic systems. Network analysis revealed downregulation of inflammation, and upregulation of neurogenesis, and neuron survival and differentiation. CONCLUSIONS: In a porcine model of TBI + HS, EV treatment was associated with an attenuation of cerebral inflammatory networks and a promotion of neurogenesis and neuroplasticity. These transcriptomic changes could explain the observed neuroprotective and neurorestorative properties associated with EV treatment