George Mazariegos - Academia.edu (original) (raw)

Papers by George Mazariegos

Clinical Liver Disease, 2021

Save the Children Hsu, Perito, and Mazariegos review justifications for prioritizing children on ... more Save the Children Hsu, Perito, and Mazariegos review justifications for prioritizing children on transplant wait lists (Table 1). Under the principle of medical utility, children should be prioritized because they would benefit from an organ for longer than many adults.

Annals of surgery, 2018

: There is an unacceptably high burden of death and disability from conditions that are treatable... more : There is an unacceptably high burden of death and disability from conditions that are treatable by surgery, worldwide and especially in low- and middle-income countries (LMICs). The major actions to improve this situation need to be taken by the surgical communities, institutions, and governments of the LMICs. The US surgical community, including the US academic surgical community, has, however, important roles to play in addressing this problem. The American Surgical Association convened a Working Group to address how US academic surgery can most effectively decrease the burden from surgically treatable conditions in LMICs. The Working Group believes that the task will be most successful (1) if the epidemiologic pattern in a given country is taken into account by focusing on those surgically treatable conditions with the highest burdens; (2) if emphasis is placed on those surgical services that are most cost-effective and most feasible to scale up; and (3) if efforts are harmonized with local priorities and with existing global initiatives, such as the World Health Assembly with its 2015 resolution on essential surgery. This consensus statement gives recommendations on how to achieve those goals through the tools of academic surgery: clinical care, training and capacity building, research, and advocacy. Through all of these, the ethical principles of maximally and transparently engaging with and deferring to the interests and needs of local surgeons and their patients are of paramount importance. Notable benefits accrue to US surgeons, trainees, and institutions that engage in global surgical activities.

Current Opinion in Organ Transplantation, 2011

Pediatric transplantation offers a unique opportunity to impact children for a lifetime. Accordin... more Pediatric transplantation offers a unique opportunity to impact children for a lifetime. Accordingly, contributors to our section have combined to offer compelling views into the latest advances in their fields or describe the opportunities for improving outcomes by better immunosuppression, improving the donor pool, tackling issues of nonadherence or describing the state of immune monitoring across organ systems.

Current Opinion in Organ Transplantation, 2009

Recent changes in medical therapy that have altered patient care include the study of omega 3 fis... more Recent changes in medical therapy that have altered patient care include the study of omega 3 fish oil-based lipid emulsion as an alternative to lipid minimization therapy [9-12]. Surgical therapies that have a role in adaptation after intestinal failure include serial transverse enteroplasty (STEP) [13]. A current review of sixteen children observed for a median time of 23 months postoperatively demonstrated a mean increase in bowel length of 91% AE 38%. After the STEP procedure, patients increased weight-forage z scores 0.03 units per month, height for age z scores 0.02 units per month

Current Opinion in Organ Transplantation, 2006

Purpose of review Despite significant progress in allograft survival in kidney, liver, and intest... more Purpose of review Despite significant progress in allograft survival in kidney, liver, and intestine recipients, long-term morbidity and mortality continue secondary to immunosuppressionrelated complications. Recent findings Starzl and others have recently postulated that exhaustiondeletion of the antidonor response accompanied by the migration of allograft passenger leukocytes allows for longterm engraftment and acquired tolerance or near tolerance, coined 'prope' tolerance by Calne. Furthermore, excessive posttransplant immunosuppression could be detrimental to the long-term objective of graft acceptance by antagonizing efficient clonal deletion. Studies have now been published with such preconditioning and minimal posttransplant immunosuppressive strategies employed successfully in pediatric liver, kidney, and intestine transplantation. The majority of patients are free from steroids, are on spaced tacrolimus monotherapy, and have benefited from a low incidence of immunosuppressive-related complications. Summary Several publications are reviewed to document both excellent patient and graft survival, along with similar or lower rejection rates compared with historical controls, achieved with less cumulative immunosuppression and, subsequently, less infection. The long-term use of such protocols over a lifetime should be of particular benefit to children, although objective documentation of such advantages will require ongoing evaluation.

Pediatric Transplantation, 2009

Pediatric Radiology, 2004

We report a patient who developed mesenteroaxial gastric volvulus after a liver transplantation. ... more We report a patient who developed mesenteroaxial gastric volvulus after a liver transplantation. We hypothesize that this complication may have been related to the ligation of the hepatogastric ligament done to mobilize the liver during hepatectomy.

Pediatric Drugs, 2010

Solid organ transplantation is a life-saving treatment for end-stage organ failure in children. I... more Solid organ transplantation is a life-saving treatment for end-stage organ failure in children. Immunosuppressant medications are used to prevent rejection of the organ transplant. However, these medications are associated with significant adverse effects that impact growth and development, quality of life (QOL), and sometimes long-term survival after transplantation. Adverse effects can differ between the immunosuppressants, but many result from the overall state of immunosuppression. Strategies to manage immunosuppressant adverse effects often involve minimizing exposure to the drugs while balancing the risk for rejection. Early recognition of immunosuppressant adverse effects may help to reduce morbidities associated with solid organ transplantation, improve QOL, and possibly increase overall patient survival. Solid organ transplantation is a viable option for treating childhood diseases that result in end-stage organ failure. The primary diseases that lead to end-stage organ failure and subsequent transplant in children are listed in tables I, II and III. According to the Organ Procurement and Transplantation Network (OPTN), 1964 pediatric patients (under the age of 18 years) received an organ transplant in the US during 2008, accounting for 7.6% of all transplants performed in the US as of 20 November 2009. The majority of these transplants were kidney (n = 773), closely followed by liver (n = 613) and heart transplants (n = 365). Although intestinal transplants were the fourth most common (n = 93), children accounted for 75.6% of all intestinal transplants performed in the US in 2008. Children comprise nearly 2% of the patients on

Investigational New Drugs, 1985

A factor of nominal molecular weight 6K-10K Daltons, isolated from bovine aorta, has previously b... more A factor of nominal molecular weight 6K-10K Daltons, isolated from bovine aorta, has previously been shown to inhibit neovascularization and tumor growth in vivo and the growth of some tumor cells as well as endothelial cells in culture. This factor, termed A-10, was tested alone and in combination with Adriamycin against TA3Ha mammary adenocarcinoma cells in tissue culture. It was found to have cytotoxicity additive to that of Adriamycin in inhibiting the growth of these cells. In vitro and animal studies show that the sequence of Adriamycin ~ A-10 is superior to either agent alone in delaying the appearance of palpable tumors after subcutaneous injection of 105 pre-treated tumor cells in the tail of strain A mice. While the growth rate of the primary tumor was not affected by such treatment, survival was prolonged to a greater degree by the this sequence than by either of these agents used alone. A-10 treatment reduced the number of metastases to the adrenal gland but not to lung, liver, or lymph nodes. It did, however, reduce the size of metastases to para-aortic lymph nodes.

Liver transplantation : official publication of the American Association for the Study of Liver Diseases and the International Liver Transplantation Society, Jan 18, 2017

Frontiers in Bioscience, 2007

The Journal of Immunology

Experimental models describe immune exhaustion in liver transplant tolerance. It is not known if ... more Experimental models describe immune exhaustion in liver transplant tolerance. It is not known if immune exhaustion is also occurs in clinical operational tolerance. We tested this in a cross-sectional cohort of pediatric liver transplant recipients with stable allograft function in the absence of immunosuppression (Operationally Tolerant, OT) in comparison to those Weaned off Immunosuppression (WI), continued on Maintenance Immunosuppression (MI) and Healthy Controls (HC). Results: In OT recipients, B cell frequencies (p <0.05) were increased and were enriched in both unswitched (p<0.005) and switched memory B cells (CD19+ IgM+ CD27+ and CD19+ IgG+ CD27+) (p<0.05) compard to MI. CD8 T cells in OT showed an increase in effector memory compared to MI (p<0.05). CD4 Treg frequencies were increased in OT compared to MI (p<0.0005). Both CD4 and CD8 T cells in OT showed an increase in cells expressing CD57, indicative of replicative senescence and these were enriched within ...

Liver Transplantation

A "central pathology" or "site" reading of biopsy slides is used in liver transplant clinical tri... more A "central pathology" or "site" reading of biopsy slides is used in liver transplant clinical trials to determine rejection. We evaluated inter-rater reliability of readings of "rejection or not" using digitized slides from the Medication Adherence in Pediatric Liver Transplant Recipients (MALT) study. 4 masked experienced pathologists read the digitized slides and then reread them after a study-specific histologic end-point development program. Agreement was expressed throughout as a Kappa or Fleiss Kappa statistic (ҡ). A ҡ > 0.6 was predefined as desirable. Readings were correlated with immunosuppressant adherence (The Medication Level Variability Index, MLVI), and maximal liver enzyme levels during the study period. Interrater agreement between site and central review in MALT, and between 4 pathologists later on, was low (ҡ=0.44, Fleiss ҡ = 0.41, respectively). Following the end-point development program, agreement improved and became acceptable (ҡ = 0.71). The final reading was better-aligned with maximal GGT levels and MLVI

Frontiers in bioscience, Jun 1, 2009

Solid Organ Transplantation in Infants and Children, 2017

Optimizing outcomes for children undergoing liver transplantation involves ongoing multidisciplin... more Optimizing outcomes for children undergoing liver transplantation involves ongoing multidisciplinary assessment of medical morbidities unique to the underlying disease and specific patient population. In3reasing understanding of cardiopulmonary and renal factors as impacting posttransplant outcomes as well as high level of heterogeneity in patient diagnoses presenting for liver transplantation requires a dynamic approach in evaluation. Technical expertise remains critical to early success of pediatric liver transplantation, and single center as well as network analysis (OPTN, SPLIT, others) has identified variation in outcomes as well as opportunities for improvement. Critical assessment and prophylaxis or intervention for infection and optimizing renal status in the early posttransplant period are critical as is timely management of surgical complications.

Pediatric Transplantation, 2021

Background: Domino liver transplantation aims to address the need to increase the liver donor sup... more Background: Domino liver transplantation aims to address the need to increase the liver donor supply. In a domino liver transplant, the domino recipient receives the explanted liver from the recipient of a traditional liver transplant. The domino donor typically requires liver transplant to correct a metabolic disorder; the explanted liver thus has a single gene defect but otherwise normal structure and function. Methods: In this review, we detail the history of domino liver transplantation, appropriate domino donor indications, the technical advances to the surgical approach, current outcomes, and future opportunities. Results: Development of de novo disease in the domino recipient has relegated adult domino liver transplant to be considered a source of marginal donor livers. However, pediatric domino liver transplant has leveraged certain metabolic disorders, especially maple syrup urine disease, in which the liver enzyme deficiency can be compensated by the systemic presence of sufficient enzyme. Advances in the surgical aspects of assuring adequate length of vasculature have improved the safety of the procedure in both domino donors and recipients. Conclusions: Pediatric domino liver transplant utilizing domino donors with specific metabolic liver diseases should be considered a viable live donor option for children awaiting liver transplant.

Frontiers in Pediatrics, 2020

COVID-19 has dramatically altered the health care landscape and disrupted global health and world... more COVID-19 has dramatically altered the health care landscape and disrupted global health and world economics in ways that are still being measured. Its impact on children with chronic conditions or those undergoing transplantation is evolving. The organ specific manifestations in children will be reviewed and treatment strategies outlined. The impact on pediatric transplantation in the United States over the initial 6 months of the pandemic has shown significant regional variation and lags persist in resumption of normal transplant activity, particularly for living related transplantation. Finally, guidelines regarding return to school will be discussed.

Transplantation Surgery, 2019

More than half a century ago, multivisceral intestinal transplantation (MVT) was undertaken exper... more More than half a century ago, multivisceral intestinal transplantation (MVT) was undertaken experimentally on canines by Starzl et al. [1, 2] despite concerns over predicting immunologic outcomes and uncertain lymphatic drainage. The graft was designed as a grape cluster with a double central stem consisting of celiac axis and superior mesenteric artery (SMA), which would allow future modifications. The venous outflow of this grape cluster was hepatopedal; it was kept intact up to or beyond the liver [1, 2]. The first human MVT was also performed by Starzl et al. in 1983 and 1989 in two pediatric cases, but clinically reproducible results awaited the introduction of tacrolimus in 1989 [3]. The reasons for early failure were allograft rejection and infection [4].