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Predictors of mortality in the critically ill cirrhotic: is Model for End Stage Liver Disease enough?
TRANSPLANTATION AND TISSUE ENGINEERING scores and identify clinical risk factors associated with increased ICU mortality in cirrhotic patients.
Donor-derived skeletal muscle precursor cells improve muscle functions in a murine model of X-linked myotubular myopathy Hyun Ju Lim, Sunyoung Joo, MD, John D Jackson, PhD, Delrae Eckman, Christopher R Pierson, MD, PhD, Martin Childers, DO, PhD, James Yoo, MD, PhD, Anthony Atala, MD, FACS Wake Forest School of Medicine, Winston-Salem, NC; The Research Institute at Nationwide Children’s Hospital, Columbus, OH; University of Washington, Seattle, WA
METHODS: We conducted a retrospective review of all cirrhotic patients admitted to the ICU between January 2013 and December 2014. Patients who received a transplant in 72 hours were excluded. Patients who were discharged or underwent a transplant (ICU Survival) were compared to patients who died in the ICU (ICU Mortality). Demographics, admission MELD scores, and clinical risk factors were recorded. Multivariate regression analysis was utilized to identify independent predictors of mortality.
INTRODUCTION: The X-linked myotubular myopathy (XLMTM) is an isogenic muscle disease characterized by the progressive wasting of skeletal muscle, weakness, and premature death. In this study we investigated whether injection of syngeneic skeletal muscle precursor cells from wild type (WT) or XLMTM knock-in (KI) mice into the gastrocnemius muscle of KI affected mice could improve skeletal muscle function.
RESULTS: Of 131 patients meeting inclusion criteria, 84 (64%) were either discharged or underwent a transplant and 47 (36%) died in the ICU. The ICU Mortality cohort had increased mean MELD, infection, mechanical ventilation, paracentesis, encephalopathy, vasopressors, dialysis, and ICU length of stay. Multivariate analysis identified mechanical ventilation and vasopressors as independent predictors of increased ICU mortality (OR: 6.49, 95% CI 2.1-19.9, p<0.01 and OR: 8.42, 95% CI 2.7-26.7, p<0.01 respectively).
METHODS: Skeletal muscle precursor cells (SkMC) were isolated from WT and KI mice. Mice were placed into 4 groups; agematched WT (positive control), KI-saline injection (negative control), KI-WT SkMC injection, and KI-KI SkMC injection. Labeled cells were injected into the gastrocnemius muscle of the hind limb. Treated mice were assessed for improved skeletal muscle function. Physiological parameters were measured prior to the start of the study and 1, 2, or 4 weeks post injection.
CONCLUSIONS: MELD score, although a widely accepted predictor of 90-day mortality in patients with cirrhosis, was not an independent predictor of increased mortality in the critically ill. MELD may be an unreliable indicator for prognosis in this population. Repopulation of primary renal cells for whole organ engineering: functional evaluations Mehran Abolbashari, MD, Mi Kyung Lee, MD, Sigrid Agcaoili, MD, Tamer Aboushwareb, MD, PhD, John D Jackson, PhD, In Kap Ko, PhD, James Yoo, MD, PhD, Anthony Atala, MD, FACS Wake Forest School of Medicine, Winston-Salem, NC
RESULTS: The diameters of the muscle fibers for the KI mice were significantly smaller than WT mice. Functional parameters for WT mice were significantly greater than KI mice. We observed that WT and KI SkMC were capable of differentiating and expressed MyoD, Myf5, and desmin; confirming skeletal muscle phenotype of SkMC. Injected labeled donor cells were found in the gastrocnemius muscle post-injection. KI mice treated with WT or KI SkMC displayed improved physiological outcomes.
INTRODUCTION: Renal transplantation is a definitive treatment for end stage renal disease (ESRD), however it is severely limited by donor shortage. Whole organ engineering based on decellularization/recellularization techniques has been proposed as an alternative approach to renal transplantation. In this study, we examined whether the recellularized porcine kidney scaffolds possess functional capabilities.
CONCLUSIONS: Our results show that KI mice receiving WT or KI derived SkMC had increased skeletal muscle mass, force generation, and nerve-induced skeletal muscle action potential amplitude. These data suggest that autologous cell therapy may provide a new therapeutic/management option for patients suffering from centronuclear myopathies.
METHODS: Primary porcine renal cells were expanded, characterized, and seeded into the cortex of decellularized renal scaffolds, followed by bioreactor perfusion for 14 days. The levels of erythropoietin (EPO) in culture media and EPO mRNA expression were determined. Electrolyte transport and albumin re-adsorption were evaluated. The activity of amino acid transport gamma glutamyl transpeptidase (GGT) or leucine aminopeptidase (LAP) (hydrolase activity) on the renal cells also was determined.
Predictors of mortality in the critically ill cirrhotic: is Model for End Stage Liver Disease enough? Alagappan Annamalai, MD, Megan Harada, Priyanka Tripuraneni, Tong Li, Bansuri Patel, Dorothy Yim, Eric Chen, Eric J Ley, MD, FACS, Nicholas Nissen, MD, FACS Cedars-Sinai Medical Center, Los Angeles, CA INTRODUCTION: The Model for End Stage Liver Disease (MELD) score estimates survival probability in patients with cirrhosis and is a key factor in assigning priority for liver transplantation. Cirrhotic patients in the ICU urgently require transplantation but are at high risk for perioperative mortality. The purpose of this study was to evaluate the predictive power of admission MELD
ª 2015 by the American College of Surgeons Published by Elsevier Inc.
RESULTS: Fluorescent microscopic results demonstrated the evidence of sodium and albumin uptake by the renal cells within the repopulated constructs. Hydrolase activity assay showed that the renal cells within the recellularized construct expressed a significant hydrolase activity, indicating that the re-organized renal structures
e34
http://dx.doi.org/10.1016/j.jamcollsurg.2015.08.387 ISSN 1072-7515/15
Donor-derived skeletal muscle precursor cells improve muscle functions in a murine model of X-linked myotubular myopathy Hyun Ju Lim, Sunyoung Joo, MD, John D Jackson, PhD, Delrae Eckman, Christopher R Pierson, MD, PhD, Martin Childers, DO, PhD, James Yoo, MD, PhD, Anthony Atala, MD, FACS Wake Forest School of Medicine, Winston-Salem, NC; The Research Institute at Nationwide Children’s Hospital, Columbus, OH; University of Washington, Seattle, WA
METHODS: We conducted a retrospective review of all cirrhotic patients admitted to the ICU between January 2013 and December 2014. Patients who received a transplant in 72 hours were excluded. Patients who were discharged or underwent a transplant (ICU Survival) were compared to patients who died in the ICU (ICU Mortality). Demographics, admission MELD scores, and clinical risk factors were recorded. Multivariate regression analysis was utilized to identify independent predictors of mortality.
INTRODUCTION: The X-linked myotubular myopathy (XLMTM) is an isogenic muscle disease characterized by the progressive wasting of skeletal muscle, weakness, and premature death. In this study we investigated whether injection of syngeneic skeletal muscle precursor cells from wild type (WT) or XLMTM knock-in (KI) mice into the gastrocnemius muscle of KI affected mice could improve skeletal muscle function.
RESULTS: Of 131 patients meeting inclusion criteria, 84 (64%) were either discharged or underwent a transplant and 47 (36%) died in the ICU. The ICU Mortality cohort had increased mean MELD, infection, mechanical ventilation, paracentesis, encephalopathy, vasopressors, dialysis, and ICU length of stay. Multivariate analysis identified mechanical ventilation and vasopressors as independent predictors of increased ICU mortality (OR: 6.49, 95% CI 2.1-19.9, p<0.01 and OR: 8.42, 95% CI 2.7-26.7, p<0.01 respectively).
METHODS: Skeletal muscle precursor cells (SkMC) were isolated from WT and KI mice. Mice were placed into 4 groups; agematched WT (positive control), KI-saline injection (negative control), KI-WT SkMC injection, and KI-KI SkMC injection. Labeled cells were injected into the gastrocnemius muscle of the hind limb. Treated mice were assessed for improved skeletal muscle function. Physiological parameters were measured prior to the start of the study and 1, 2, or 4 weeks post injection.
CONCLUSIONS: MELD score, although a widely accepted predictor of 90-day mortality in patients with cirrhosis, was not an independent predictor of increased mortality in the critically ill. MELD may be an unreliable indicator for prognosis in this population. Repopulation of primary renal cells for whole organ engineering: functional evaluations Mehran Abolbashari, MD, Mi Kyung Lee, MD, Sigrid Agcaoili, MD, Tamer Aboushwareb, MD, PhD, John D Jackson, PhD, In Kap Ko, PhD, James Yoo, MD, PhD, Anthony Atala, MD, FACS Wake Forest School of Medicine, Winston-Salem, NC
RESULTS: The diameters of the muscle fibers for the KI mice were significantly smaller than WT mice. Functional parameters for WT mice were significantly greater than KI mice. We observed that WT and KI SkMC were capable of differentiating and expressed MyoD, Myf5, and desmin; confirming skeletal muscle phenotype of SkMC. Injected labeled donor cells were found in the gastrocnemius muscle post-injection. KI mice treated with WT or KI SkMC displayed improved physiological outcomes.
INTRODUCTION: Renal transplantation is a definitive treatment for end stage renal disease (ESRD), however it is severely limited by donor shortage. Whole organ engineering based on decellularization/recellularization techniques has been proposed as an alternative approach to renal transplantation. In this study, we examined whether the recellularized porcine kidney scaffolds possess functional capabilities.
CONCLUSIONS: Our results show that KI mice receiving WT or KI derived SkMC had increased skeletal muscle mass, force generation, and nerve-induced skeletal muscle action potential amplitude. These data suggest that autologous cell therapy may provide a new therapeutic/management option for patients suffering from centronuclear myopathies.
METHODS: Primary porcine renal cells were expanded, characterized, and seeded into the cortex of decellularized renal scaffolds, followed by bioreactor perfusion for 14 days. The levels of erythropoietin (EPO) in culture media and EPO mRNA expression were determined. Electrolyte transport and albumin re-adsorption were evaluated. The activity of amino acid transport gamma glutamyl transpeptidase (GGT) or leucine aminopeptidase (LAP) (hydrolase activity) on the renal cells also was determined.
Predictors of mortality in the critically ill cirrhotic: is Model for End Stage Liver Disease enough? Alagappan Annamalai, MD, Megan Harada, Priyanka Tripuraneni, Tong Li, Bansuri Patel, Dorothy Yim, Eric Chen, Eric J Ley, MD, FACS, Nicholas Nissen, MD, FACS Cedars-Sinai Medical Center, Los Angeles, CA INTRODUCTION: The Model for End Stage Liver Disease (MELD) score estimates survival probability in patients with cirrhosis and is a key factor in assigning priority for liver transplantation. Cirrhotic patients in the ICU urgently require transplantation but are at high risk for perioperative mortality. The purpose of this study was to evaluate the predictive power of admission MELD
ª 2015 by the American College of Surgeons Published by Elsevier Inc.
RESULTS: Fluorescent microscopic results demonstrated the evidence of sodium and albumin uptake by the renal cells within the repopulated constructs. Hydrolase activity assay showed that the renal cells within the recellularized construct expressed a significant hydrolase activity, indicating that the re-organized renal structures
e34
http://dx.doi.org/10.1016/j.jamcollsurg.2015.08.387 ISSN 1072-7515/15