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

Hospital readmission for acute kidney injury is independently associated with de novo end-stage renal disease after liver transplantation

End-stage renal disease (ESRD) after liver transplantation (LT) is associated with high morbidity and mortality. The consequences of hospitalizations for post-LT acute kidney injury (AKI) are poorly understood. Using linked Medicare claims and transplant registry data, we analyzed adult liver alone recipients not receiving pre-transplant dialysis between 1/1/2007-12/31/2016. Covariate-adjusted Cox proportional hazards models stratified by center evaluated factors associated with AKI readmission during the first post-LT year, and whether AKI readmission was associated with de novo early (<1 y) or late (≥1 y) ESRD post-LT. The cohort included 10,559 patients and was 64.5% male, 72.5% White, 8.1% Black and 14.0% Hispanic with median age 62 years. Overall, 2,875 (27.2%) patients had ≥1 AKI hospitalization during the first year. eGFR at LT was associated with AKI readmission (aHR 1.16 per 10 mL/min/1.73m2 decrease; p<0.001). The aHR for early ESRD in patients with ≥1 AKI readmission <90 days post-LT was 1.90 (p<0.001). The aHRs for late ESRD with 1 and ≥2 prior AKI readmissions were 1.57 and 2.80 respectively (p<0.001). AKI readmissions in the first post-LT year impact over one-quarter of recipients. These increase the risk of subsequent ESRD, but may represent an opportunity to intervene and mitigate further renal dysfunction.End-stage renal disease (ESRD) after liver transplantation (LT) is associated with high morbidity and mortality. The consequences of hospitalizations for post-LT acute kidney injury (AKI) are poorly understood. Using linked Medicare claims and transplant registry data, we analyzed adult liver alone recipients not receiving pre-transplant dialysis between 1/1/2007-12/31/2016. Covariate-adjusted Cox proportional hazards models stratified by center evaluated factors associated with AKI readmission during the first post-LT year, and whether AKI readmission was associated with de novo early (<1 y) or late (≥1 y) ESRD post-LT. The cohort included 10,559 patients and was 64.5% male, 72.5% White, 8.1% Black and 14.0% Hispanic with median age 62 years. Overall, 2,875 (27.2%) patients had ≥1 AKI hospitalization during the first year. eGFR at LT was associated with AKI readmission (aHR 1.16 per 10 mL/min/1.73m2 decrease; p<0.001). The aHR for early ESRD in patients with ≥1 AKI readmission <90 days post-LT was 1.90 (p<0.001). The aHRs for late ESRD with 1 and ≥2 prior AKI readmissions were 1.57 and 2.80 respectively (p<0.001). AKI readmissions in the first post-LT year impact over one-quarter of recipients. These increase the risk of subsequent ESRD, but may represent an opportunity to intervene and mitigate further renal dysfunction

Real-world evidence for factors associated with maintenance treatment practices among U.S. adults with autoimmune hepatitis

While avoidance of long-term corticosteroids is a common objective in the management of autoimmune hepatitis (AIH), prolonged immunosuppression is usually required to prevent disease progression. This study investigates the patient and provider factors associated with treatment patterns in U.S. patients with AIH.BACKGROUND AIMSWhile avoidance of long-term corticosteroids is a common objective in the management of autoimmune hepatitis (AIH), prolonged immunosuppression is usually required to prevent disease progression. This study investigates the patient and provider factors associated with treatment patterns in U.S. patients with AIH.A retrospective cohort of adults with incident and prevalent AIH was identified from Optum's de-identified Clinformatics® Data Mart Database. All patients were followed for at least 2 years, with exposures assessed during the first year and treatment patterns during the second. Patient and provider factors associated with corticosteroid-sparing monotherapy and cumulative prednisone use were identified using multivariable logistic and linear regression, respectively.The cohort was 81.2% female, 66.3% White, 11.3% Black, 11.2% Hispanic and with median age 61 years. Among 2,203 patients with ≥1 AIH prescription fill, 83.1% received a single regimen for >6 months of the observation year, which included 52.2% azathioprine monotherapy, 16.9% azathioprine/prednisone and 13.3% prednisone monotherapy. Budesonide use was uncommon (2.1% combination, 1.9% monotherapy). Hispanic ethnicity (aOR 0.56; p=0.006), cirrhosis (aOR 0.73; p=0.019), osteoporosis (aOR 0.54; p=0.001) and top quintile of provider AIH experience (aOR 0.66; p=0.005) were independently associated with lower use of corticosteroid-sparing monotherapy. Cumulative prednisone use was greater with diabetes (+441 mg/year; p=0.004), osteoporosis (+749 mg/year; p6 months of the observation year, which included 52.2% azathioprine monotherapy, 16.9% azathioprine/prednisone and 13.3% prednisone monotherapy. Budesonide use was uncommon (2.1% combination, 1.9% monotherapy). Hispanic ethnicity (aOR 0.56; p=0.006), cirrhosis (aOR 0.73; p=0.019), osteoporosis (aOR 0.54; p=0.001) and top quintile of provider AIH experience (aOR 0.66; p=0.005) were independently associated with lower use of corticosteroid-sparing monotherapy. Cumulative prednisone use was greater with diabetes (+441 mg/year; p=0.004), osteoporosis (+749 mg/year; p<0.001) and highly experienced providers (+556 mg/year; p<0.001).Long-term prednisone therapy remains common, and unexpectedly higher among patients with comorbidities potentially aggravated by corticosteroids. The greater use of corticosteroid-based therapy with highly experienced providers may reflect more treatment-refractory disease.CONCLUSIONSLong-term prednisone therapy remains common, and unexpectedly higher among patients with comorbidities potentially aggravated by corticosteroids. The greater use of corticosteroid-based therapy with highly experienced providers may reflect more treatment-refractory disease

Early Treatment with Exosomes following Traumatic Brain Injury and Hemorrhagic Shock in a Swine Model Promotes Transcriptional Changes associated with Neuroprotection

BACKGROUND: We have shown that administration of mesenchymal stem cell (MSC)-derived exosomes (single dose given within 1 hour) in models of traumatic brain injury (TBI) and hemorrhagic shock (HS) is neuroprotective. The precise mechanisms responsible for the neuroprotection are not fully understood. This study was designed to investigate the transcriptomic changes in the brain that are associated with this treatment strategy. METHODS: Yorkshire swine (40-45 kg) were subjected to a severe TBI (12-mm cortical impact) and HS (40% estimated total blood volume). One hour into shock, animals were randomized (n=5/cohort) to receive either lactated Ringer\u27s (LR; 5mL) or exosomes suspended in LR (LR+EXO; 1 × 10 exosome particles in 5 mL LR). Animals then underwent additional shock (1 hr) followed by normal saline resuscitation. After 6 hours of observation, brain swelling (% increase compared to the uninjured side) and lesion size (mm) were assessed. Peri-injured brain tissue was processed for RNA sequencing, analyzed with high through-put RNA-seq data analysis, and results compared between control and experimental groups. RESULTS: Exosome treatment significantly increased (p \u3c 0.005) gene expression associated with neurogenesis, neuronal development, synaptogenesis, and neuroplasticity. It also significantly reduced (p \u3c 0.005) genes associated with stroke, neuroinflammation, neuroepithelial cell proliferation and non-neuronal cell proliferation contributing to reactive gliosis. Exosomes treatment also significantly increased (p \u3c 0.005) the genes that are associated with the stability of blood-brain barrier. CONCLUSIONS: Administration of a single dose of exosomes induces transcriptomic changes suggestive of neuroprotection. Their use as a treatment of TBI is promising, and requires further investigation for human translation. LEVEL OF EVIDENCE: Not applicable (pre-clinical study)

Early Single-Dose Treatment with Exosomes Provides Neuroprotection and Improves Blood-Brain Barrier Integrity in Swine Model of Traumatic Brain Injury and Hemorrhagic Shock

BACKGROUND: Administration of human mesenchymal stem cell (MSC)-derived exosomes can enhance neurorestoration in models of traumatic brain injury (TBI) and hemorrhagic shock (HS). The impact of early treatment with MSC-derived exosomes on brain injury in a large animal model remains unknown. We sought to evaluate the impact of early single-dose exosome treatment on brain swelling and lesion size, blood-based cerebral biomarkers, and blood-brain barrier (BBB) integrity. METHODS: Female Yorkshire swine were subjected to a severe TBI (12-mm cortical impact) and HS (40% estimated total blood volume). One hour into shock, animals were randomized (n=5/cohort) to receive either lactated Ringer\u27s (LR; 5mL) or LR + exosomes (LR+EXO; 1 x 10 exosome particles in 5 mL LR). Animals then underwent additional shock (1 hr) followed by normal saline resuscitation. After 6 hours of observation, brain swelling (% increase compared to the uninjured side) and lesion size (mm) were assessed. Cerebral hemodynamics and blood-based biomarkers of brain injury were compared. Immunofluorescence and RNA sequencing with differential gene expression and pathway analysis were used to assess the integrity of the peri-lesion BBB. RESULTS: Exosome-treated animals had significantly less (p \u3c 0.05) brain swelling and smaller lesion size. They also had significantly decreased (p \u3c 0.05) intracranial pressures and increased cerebral perfusion pressures. Exosome-treated animals had significantly decreased (p \u3c 0.05) albumin extravasation and significantly higher (p \u3c 0.05) laminin, claudin-5, and zonula occludens-1 levels. Differential gene expression and pathway analysis confirmed these findings. Serum glial fibrillary acidic protein levels were also significantly lower (p\u3c0.05) in the exosome-treated cohort at the end of the experiment. CONCLUSIONS: In a large animal model of TBI and HS, early treatment with a single dose of MSC-derived exosomes significantly attenuates brain swelling and lesion size, decreases levels of blood-based cerebral biomarkers, and improves BBB integrity. LEVEL OF EVIDENCE: Not applicable (pre-clinical study)