156 results on '"A. Osama Gaber"'
Search Results
2. Predicting a Positive Antibody Response After 2 SARS-CoV-2 mRNA Vaccines in Transplant Recipients: A Machine Learning Approach With External Validation
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Jennifer L. Alejo, Jonathan Mitchell, Teresa P.-Y. Chiang, Amy Chang, Aura T. Abedon, William A. Werbel, Brian J. Boyarsky, Laura B. Zeiser, Robin K. Avery, Aaron A.R. Tobian, Macey L. Levan, Daniel S. Warren, Allan B. Massie, Linda W. Moore, Ashrith Guha, Howard J. Huang, Richard J. Knight, Ahmed Osama Gaber, Rafik Mark Ghobrial, Jacqueline M. Garonzik-Wang, Dorry L. Segev, and Sunjae Bae
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Vaccines ,Vaccines, Synthetic ,Transplantation ,COVID-19 Vaccines ,SARS-CoV-2 ,COVID-19 ,Mycophenolic Acid ,Antibodies, Viral ,Transplant Recipients ,Machine Learning ,Antibody Formation ,Humans ,mRNA Vaccines ,BNT162 Vaccine ,Immunosuppressive Agents - Abstract
Solid organ transplant recipients (SOTRs) are less likely to mount an antibody response to SARS-CoV-2 mRNA vaccines. Understanding risk factors for impaired vaccine response can guide strategies for antibody testing and additional vaccine dose recommendations.Using a nationwide observational cohort of 1031 SOTRs, we created a machine learning model to explore, identify, rank, and quantify the association of 19 clinical factors with antibody responses to 2 doses of SARS-CoV-2 mRNA vaccines. External validation of the model was performed using a cohort of 512 SOTRs at Houston Methodist Hospital.Mycophenolate mofetil use, a shorter time since transplant, and older age were the strongest predictors of a negative antibody response, collectively contributing to 76% of the model's prediction performance. Other clinical factors, including transplanted organ, vaccine type (mRNA-1273 versus BNT162b2), sex, race, and other immunosuppressants, showed comparatively weaker associations with an antibody response. This model showed moderate prediction performance, with an area under the receiver operating characteristic curve of 0.79 in our cohort and 0.67 in the external validation cohort. An online calculator based on our prediction model is available at http://transplantmodels.com/covidvaccine/ .Our machine learning model helps understand which transplant patients need closer follow-up and additional doses of vaccine to achieve protective immunity. The online calculator based on this model can be incorporated into transplant providers' practice to facilitate patient-centric, precision risk stratification and inform vaccination strategies among SOTRs.
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- 2022
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3. Survival following liver transplantation for locally advanced, unresectable intrahepatic cholangiocarcinoma
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Ashish Saharia, Mark J. Hobeika, Linda W. Moore, Milind Javle, Robert S McFadden, Edward A. Graviss, Constance M. Mobley, Nam C. Yu, Robert McMillan, Keri E Lunsford, R. Mark Ghobrial, Joy V. Nolte Fong, Ahmed Kaseb, Jean Nicolas Vauthey, Mukul K. Divatia, Maen Abdelrahim, Duc T. Nguyen, A. Osama Gaber, Sudha Kodali, Kirk Heyne, David W. Victor, and Akshay Shetty
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Transplantation ,medicine.medical_specialty ,Tumor size ,business.industry ,medicine.medical_treatment ,Locally advanced ,Liver transplantation ,Gastroenterology ,Systemic therapy ,Neoadjuvant Therapy ,Liver Transplantation ,Cholangiocarcinoma ,Bile Ducts, Intrahepatic ,Bile Duct Neoplasms ,Internal medicine ,medicine ,Humans ,Immunology and Allergy ,Population study ,Pharmacology (medical) ,business ,Contraindication ,Neoadjuvant therapy ,Intrahepatic Cholangiocarcinoma - Abstract
Intrahepatic cholangiocarcinoma (iCCA) has previously been considered a contraindication to liver transplantation (LT). However, recent series showed favorable outcomes for LT after neoadjuvant therapy. Our center developed a protocol for neoadjuvant therapy and LT for patients with locally advanced, unresectable iCCA in 2010. Patients undergoing LT were required to demonstrate disease stability for 6 months on neoadjuvant therapy with no extrahepatic disease. During the study period, 32 patients were listed for LT and 18 patients underwent LT. For transplanted patients, the median number of iCCA tumors was 2, and the median cumulative tumor diameter was 10.4 cm. Patients receiving LT had an overall survival at 1-, 3-, and 5-years of 100%, 71%, and 57%. Recurrences occurred in seven patients and were treated with systemic therapy and resection. The study population had a higher than expected proportion of patients with genetic alterations in fibroblast growth factor receptor (FGFR) and DNA damage repair pathways. These data support LT as a treatment for highly selected patients with locally advanced, unresectable iCCA. Further studies to identify criteria for LT in iCCA and factors predicting survival are warranted.
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- 2022
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4. Outcomes of a High-Volume Organ Procurement Organization in the Era of Increasing Donation After Circulatory Death
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Mark J. Hobeika, Terri Menser, Kevin Myer, Adriana Lopez, Asad F. Shaikh, Lauren Quinn, Chris Curran, R. Patrick Wood, R. Mark Ghobrial, and A. Osama Gaber
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Death ,Transplantation ,Brain Death ,Tissue and Organ Procurement ,Graft Survival ,Humans ,Organ Transplantation ,Warm Ischemia ,Tissue Donors ,Retrospective Studies - Abstract
Introduction: Donation after circulatory death (DCD) is rapidly increasing in the United States. Detailed data outlining the process from referral to organ transplantation is lacking. Project Aims: We sought to quantify differences at each stage along the referral to donation pathway by donor type. Additionally, we examined factors associated with successful DCD organ utilization. Design: This program evaluation analyzed data from a single organ procurement organization in 2018 to assess demographic and clinical predictors of progression through the donation process, including the role of first-person authorization in DCD. Descriptive statistics were examined by donation stage for demographic characteristics using chi-square; univariate and multivariate logistic regression was used to model predictors of utilization and authorization by organ type, respectively. Results: There were 2466 organ donation referrals during 2018, including 575 donations after brainstem death (DBD), 1890 controlled DCD referrals, and 1 uncontrolled DCD referral. Univariate and multivariate logistic regression models highlighted differences in authorization rates by donor type (DCD vs DBD) and by age, race, and ethnicity. Next-of-kin authorization was declined in 23% of first-person authorized potential DCD, highlighting issues related to the role of donor registration in DCD. Pre-mortem heparin administration was predictive of DCD organ utilization; donor age and warm ischemia time of less than 30 min was statistically significantly associated with DCD extra-renal organ utilization. Conclusion: These results provided insight into strategies for increasing authorization and transplantation of organs from DCD donors and identified areas of improvement for process standardization and policy development.
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- 2022
5. Impact of Protease Inhibitor-Based Antiretroviral Therapy on Tacrolimus Intrapatient Variability in HIV-Positive Kidney Transplant Recipients
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Samantha A. Kuten, Ian Dunne, Duc T. Nguyen, Edward A. Graviss, Mark J. Hobeika, A. Osama Gaber, Anna Curtis, and Megan H Cooper
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Adult ,Graft Rejection ,Male ,medicine.medical_specialty ,medicine.medical_treatment ,Population ,Human immunodeficiency virus (HIV) ,HIV Infections ,medicine.disease_cause ,Gastroenterology ,Kidney transplant ,Tacrolimus ,Cohort Studies ,Internal medicine ,mental disorders ,medicine ,Humans ,Drug Interactions ,Protease inhibitor (pharmacology) ,education ,Retrospective Studies ,Immunosuppression Therapy ,Transplantation ,education.field_of_study ,business.industry ,Immunosuppression ,HIV Protease Inhibitors ,Middle Aged ,Kidney Transplantation ,Antiretroviral therapy ,Transplant Recipients ,Cohort ,Female ,Surgery ,business ,Immunosuppressive Agents - Abstract
Background Human immunodeficiency virus (HIV)-positive kidney transplant (KT) recipients have been shown to experience higher rejection rates due in part to drug-drug interactions between antiretroviral therapy (ART) and immunosuppression regimens. High tacrolimus (FK) intrapatient variability (IPV) is associated with inferior outcomes in KT. The purpose of this study was to determine the impact of protease inhibitor (PI)-based ART on FK IPV and graft outcomes. Methods We performed a single-center review of HIV-positive KT recipients from 2007 to 2017. Percentage coefficient of variation (%CV = (σ/μ) × 100; σ, median; μ, standard deviation) was calculated for FK IPV. FK IPV at 6 and 12 months, graft function, and immune outcomes in PI-based vs non-PI-based KT recipients were compared. Results A total of 23 HIV-positive KT patients were identified, of whom 10 were maintained on PI-based ART. Median IPV for the entire cohort at 6 and 12 months was 35.8% and 41%, respectively. Patients on PI-based regimens were proportionally more likely to experience high IPV at both time points. Median FK IPV was numerically higher at 6 months (37.3% vs 26.8%, P = .11) and significantly higher at 12 months (57.8% vs 30.9%, P = .01) for patients on PI-based regimens. Lastly, inferior graft function was observed in PI-based patients. Conclusion Our data suggest that PI-based ART is associated with a higher degree of FK IPV, which may contribute to worsening graft function. Larger studies are warranted to determine the impact of PI-based ART on FK IPV and graft outcomes in this population.
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- 2021
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6. Delayed graft function and acute rejection following HLA-incompatible living donor kidney transplantation
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Enrico Benedetti, Arjang Djamali, Madeleine M. Waldram, Kenneth L. Brayman, Stanley C. Jordan, Michael A. Rees, Jacqueline Garonzik-Wang, Lloyd E. Ratner, Matthew Cooper, Eliot Heher, Robert A. Montgomery, Jane J. Long, Jose Oberholzer, Christopher L. Marsh, George S. Lipkowitz, Marc L. Melcher, Adel Bozorgzadeh, Ty B. Dunn, Karina Covarrubias, Mark D. Stegall, Jason R. Wellen, Ron Shapiro, Jennifer Verbesey, Babak J. Orandi, John P. Roberts, Jose M. El-Amm, Debra L. Sudan, Allan B. Massie, R. Pelletier, Bashir R. Sankari, David A. Gerber, Pooja Singh, Marc P. Posner, Kyle R. Jackson, Tomasz Kozlowski, Dorry L. Segev, Jennifer D. Motter, Francis L. Weng, Sandip Kapur, A. Osama Gaber, Beatrice P. Concepcion, and J. Harold Helderman
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Graft Rejection ,medicine.medical_specialty ,Preoperative counseling ,Urology ,Delayed Graft Function ,Human leukocyte antigen ,030230 surgery ,Kidney transplant ,Living donor ,Article ,03 medical and health sciences ,0302 clinical medicine ,Risk Factors ,Living Donors ,medicine ,Humans ,Immunology and Allergy ,Pharmacology (medical) ,Kidney transplantation ,Retrospective Studies ,Transplantation ,business.industry ,Graft Survival ,medicine.disease ,Kidney Transplantation ,Histocompatibility ,Cohort ,business - Abstract
Incompatible living donor kidney transplant recipients (ILDKTr) have pre-existing donor-specific antibody (DSA) that, despite desensitization, may persist or reappear with resulting consequences, including delayed graft function (DGF) and acute rejection (AR). To quantify the risk of DGF and AR in ILDKT and downstream effects, we compared 1406 ILDKTr to 17 542 compatible LDKT recipients (CLDKTr) using a 25-center cohort with novel SRTR linkage. We characterized DSA strength as positive Luminex, negative flow crossmatch (PLNF); positive flow, negative cytotoxic crossmatch (PFNC); or positive cytotoxic crossmatch (PCC). DGF occurred in 3.1% of CLDKT, 3.5% of PLNF, 5.7% of PFNC, and 7.6% of PCC recipients, which translated to higher DGF for PCC recipients (aOR = 1.03 1.682.72 ). However, the impact of DGF on mortality and DCGF risk was no higher for ILDKT than CLDKT (p interaction > .1). AR developed in 8.4% of CLDKT, 18.2% of PLNF, 21.3% of PFNC, and 21.7% of PCC recipients, which translated to higher AR (aOR PLNF = 1.45 2.093.02 ; PFNC = 1.67 2.403.46 ; PCC = 1.48 2.243.37 ). Although the impact of AR on mortality was no higher for ILDKT than CLDKT (p interaction = .1), its impact on DCGF risk was less consequential for ILDKT (aHR = 1.34 1.621.95 ) than CLDKT (aHR = 1.96 2.292.67 ) (p interaction = .004). Providers should consider these risks during preoperative counseling, and strategies to mitigate them should be considered.
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- 2021
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7. Renal Function Improvement Following ANG-3777 Treatment in Patients at High Risk for Delayed Graft Function After Kidney Transplantation
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Matthew Cooper, Weizhong Cal, Michael A. Yamin, Jonathan S. Bromberg, Tracy J. Mayne, A. Osama Gaber, Itzhak D. Goldberg, and Matthew R. Weir
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Adult ,Male ,medicine.medical_specialty ,Time Factors ,medicine.medical_treatment ,Urology ,Delayed Graft Function ,Renal function ,Thiophenes ,Kidney ,Placebo ,chemistry.chemical_compound ,Double-Blind Method ,medicine ,Humans ,Kidney surgery ,Dialysis ,Kidney transplantation ,Aged ,Transplantation ,Creatinine ,business.industry ,Acute kidney injury ,Recovery of Function ,Acute Kidney Injury ,Middle Aged ,Original Clinical Science—General ,medicine.disease ,Kidney Transplantation ,United States ,Urodynamics ,Treatment Outcome ,chemistry ,ComputingMethodologies_DOCUMENTANDTEXTPROCESSING ,Pyrazoles ,Female ,business ,Glomerular Filtration Rate - Abstract
Supplemental Digital Content is available in the text., Background. Patients (20%–50%) undergoing renal transplantation experience acute kidney injury resulting in delayed graft function. ANG-3777 is an hepatocyte growth factor mimetic that binds to the c-MET receptor. In animal models, ANG-3777 decreases apoptosis, increases proliferation, and promotes organ repair and function. Methods. This was a randomized, double-blind, placebo-controlled, phase 2 trial of patients undergoing renal transplantation with
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- 2021
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8. Premature Death in Kidney Transplant Recipients: The Time for Trials is Now
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Amanda J. Vinson, Sunita Singh, Steven Chadban, David Cherney, Osama Gaber, John S. Gill, Erika Helgeson, Charles A. Herzog, Meg Jardine, Vivekanand Jha, Bertram L. Kasiske, Roslyn B. Mannon, Erin D. Michos, Amy K. Mottl, Kristin Newby, Prabir Roy-Chaudhury, Deirdre Sawinski, Adnan Sharif, Vikas S. Sridhar, Katherine R. Tuttle, David M. Vock, and Arthur Matas
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Nephrology ,Mortality, Premature ,Perspective ,Graft Survival ,Humans ,General Medicine ,Kidney Transplantation ,Transplant Recipients - Published
- 2022
9. Delayed Implantation of Pumped Kidneys Decreases Renal Allograft Futility in Combined Liver–Kidney Transplantation
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Gabriel M. Danovitch, Ronald W. Busuttil, Ashish Saharia, Keri E. Lunsford, Michael P. Harlander-Locke, Stephanie G. Yi, Mark J. Hobeika, Vatche G. Agopian, A. Osama Gaber, R. Mark Ghobrial, Ali Zarrinpar, Xian Chang Li, Richard J. Knight, Jeffrey L. Veale, Douglas G. Farmer, Edward A. Graviss, H. Albin Gritsch, Hemangshu Podder, Duc T. Nguyen, Fady M. Kaldas, and Constance M. Mobley
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Graft Rejection ,Male ,medicine.medical_specialty ,Time Factors ,medicine.medical_treatment ,Urology ,030230 surgery ,Kidney ,Time-to-Treatment ,law.invention ,End Stage Liver Disease ,03 medical and health sciences ,Liver disease ,0302 clinical medicine ,law ,Humans ,Transplantation, Homologous ,Medicine ,Renal Insufficiency ,Dialysis ,Aged ,Retrospective Studies ,Transplantation ,business.industry ,Cold Ischemia ,Graft Survival ,Retrospective cohort study ,Organ Preservation ,Perioperative ,Middle Aged ,Allografts ,medicine.disease ,Kidney Transplantation ,Intensive care unit ,Liver Transplantation ,Perfusion ,Treatment Outcome ,medicine.anatomical_structure ,Feasibility Studies ,Female ,030211 gastroenterology & hepatology ,Hemodialysis ,business ,Medical Futility - Abstract
Background Combined liver-kidney transplantation (CLKT) improves survival for liver transplant recipients with renal dysfunction; however, the tenuous perioperative hemodynamic and metabolic milieu in high-acuity CLKT recipients increases delayed graft function and kidney allograft failure. We sought to analyze whether delayed KT through pumping would improve kidney outcomes following CLKT. Methods A retrospective analysis (University of California Los Angeles [n = 145], Houston Methodist Hospital [n = 79]) was performed in all adults receiving CLKT at 2 high-volume transplant centers from February 2004 to January 2017, and recipients were analyzed for patient and allograft survival as well as renal outcomes following CLKT. Results A total of 63 patients (28.1%) underwent delayed implantation of pumped kidneys during CLKT (dCLKT) and 161 patients (71.9%) received early implantation of nonpumped kidneys during CLKT (eCLKT). Most recipients were high-acuity with median biologic model of end-stage liver disease (MELD) score of, 35 for dCLKT and 34 for eCLKT (P = ns). Pretransplant, dCLKT had longer intensive care unit stay, were more often intubated, and had greater vasopressor use. Despite this, dCLKT exhibited improved 1-, 3-, and 5-year patient and kidney survival (P = 0.02) and decreased length of stay (P = 0.001), kidney allograft failure (P = 0.012), and dialysis duration (P = 0.031). This reduced kidney allograft futility (death or continued need for hemodialysis within 3 mo posttransplant) for dCLKT (6.3%) compared with eCLKT (19.9%) (P = 0.013). Conclusions Delayed implantation of pumped kidneys is associated with improved patient and renal allograft survival and decreased hospital length of stay despite longer kidney cold ischemia. These data should inform the ethical debate as to the futility of performing CLKT in high-acuity recipients.
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- 2020
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10. Center-level Variation in HLA-incompatible Living Donor Kidney Transplantation Outcomes
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Francis L. Weng, Jacqueline Garonzik-Wang, Matthew Cooper, Jane Long, Eliot Heher, Stanley C. Jordan, Jennifer D. Motter, George S. Lipkowitz, Michael A. Rees, John P. Roberts, Jennifer Verbesey, Pooja Singh, Sandip Kapur, Lloyd E. Ratner, Jennifer K. Chen, David A. Gerber, Tomasz Kozlowski, Mark D. Stegall, Madeleine M. Waldram, Bashir R. Sankari, Niraj M. Desai, Dorry L. Segev, A. Osama Gaber, Jose Oberholzer, Babak J. Orandi, Jose M. El-Amm, Jason R. Wellen, Debra L. Sudan, Adel Bozorgzadeh, R. Pelletier, Enrico Benedetti, Robert A. Montgomery, Mary G. Bowring, Kenneth L. Brayman, Kyle R. Jackson, Marc P. Posner, Beatrice P. Concepcion, J. Harold Helderman, Allan B. Massie, Ty B. Dunn, Christopher L. Marsh, Marc L. Melcher, Karina Covarrubias, Arjang Djamali, and Ron Shapiro
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Adult ,Graft Rejection ,Male ,medicine.medical_specialty ,Time Factors ,Human leukocyte antigen ,030230 surgery ,Risk Assessment ,Living donor ,Article ,03 medical and health sciences ,0302 clinical medicine ,Highly sensitized ,HLA Antigens ,Isoantibodies ,Risk Factors ,Internal medicine ,Living Donors ,medicine ,Humans ,Registries ,Healthcare Disparities ,Practice Patterns, Physicians' ,Kidney transplantation ,Quality Indicators, Health Care ,Transplantation ,business.industry ,Proportional hazards model ,Graft Survival ,Hazard ratio ,Middle Aged ,medicine.disease ,Kidney Transplantation ,United States ,Treatment Outcome ,Histocompatibility ,Cohort ,Female ,030211 gastroenterology & hepatology ,business ,Immunosuppressive Agents - Abstract
BACKGROUND Desensitization protocols for HLA-incompatible living donor kidney transplantation (ILDKT) vary across centers. The impact of these, as well as other practice variations, on ILDKT outcomes remains unknown. METHODS We sought to quantify center-level variation in mortality and graft loss following ILDKT using a 25-center cohort of 1358 ILDKT recipients with linkage to Scientific Registry of Transplant Recipients for accurate outcome ascertainment. We used multilevel Cox regression with shared frailty to determine the variation in post-ILDKT outcomes attributable to between-center differences and to identify any center-level characteristics associated with improved post-ILDKT outcomes. RESULTS After adjusting for patient-level characteristics, only 6 centers (24%) had lower mortality and 1 (4%) had higher mortality than average. Similarly, only 5 centers (20%) had higher graft loss and 2 had lower graft loss than average. Only 4.7% of the differences in mortality (P < 0.01) and 4.4% of the differences in graft loss (P < 0.01) were attributable to between-center variation. These translated to a median hazard ratio of 1.36 for mortality and 1.34 of graft loss for similar candidates at different centers. Post-ILDKT outcomes were not associated with the following center-level characteristics: ILDKT volume and transplanting a higher proportion of highly sensitized, prior transplant, preemptive, or minority candidates. CONCLUSIONS Unlike most aspects of transplantation in which center-level variation and volume impact outcomes, we did not find substantial evidence for this in ILDKT. Our findings support the continued practice of ILDKT across these diverse centers.
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- 2020
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11. Outcomes of Liver Transplantation for Hepatocellular Carcinoma Beyond the University of California San Francisco Criteria: A Single-center Experience
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Mukul K. Divatia, Duc T. Nguyen, Robert S. McFadden, David W. Victor, Andrea Duchini, Constance M. Mobley, Julius Balogh, R. Mark Ghobrial, Kirk Heyne, A. Osama Gaber, Victor Ankoma-Sey, Howard Paul Monsour, Keri E. Lunsford, Maha Boktour, Chukwuma Egwim, Joseph S. Galati, Ashish Saharia, and Edward A. Graviss
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Ablation Techniques ,Male ,Oncology ,medicine.medical_specialty ,Carcinoma, Hepatocellular ,Time Factors ,Liver tumor ,medicine.medical_treatment ,Antineoplastic Agents ,030230 surgery ,Liver transplantation ,Single Center ,Disease-Free Survival ,03 medical and health sciences ,0302 clinical medicine ,Risk Factors ,Internal medicine ,medicine ,Carcinoma ,Humans ,Aged ,Neoplasm Staging ,Retrospective Studies ,Transplantation ,Chemotherapy ,business.industry ,Patient Selection ,Optimal treatment ,Liver Neoplasms ,Retrospective cohort study ,Middle Aged ,Sorafenib ,medicine.disease ,Neoadjuvant Therapy ,digestive system diseases ,Liver Transplantation ,Tumor Burden ,Liver ,Chemotherapy, Adjuvant ,Hepatocellular carcinoma ,Disease Progression ,Female ,030211 gastroenterology & hepatology ,Neoplasm Recurrence, Local ,business ,Follow-Up Studies - Abstract
Hepatocellular carcinoma (HCC) is the most common primary malignant liver tumor. Currently, liver transplantation may be the optimal treatment for HCC in cirrhotic patients. Patient selection is currently based on tumor size. We developed a program to offer liver transplantation to selected patients with HCC outside of traditional criteria.Retrospective review for patients transplanted with HCC between April 2008 and June 2017. Patients were grouped by tumor size according to Milan, University of California San Francisco (UCSF), and outside UCSF criteria. Patient demographics, laboratory values, and outcomes were compared. Patients radiographically outside Milan criteria were selected based on tumor control with locoregional therapy (LRT) and 9 months of stability from LRT. α-fetoprotein values were not exclusionary.Two hundred twenty HCC patients were transplanted, 138 inside Milan, 23 inside UCSF, and 59 beyond UCSF criteria. Patient survival was equivalent at 1, 3, or 5 years despite pathologic tumor size. Waiting time to transplantation was not significantly different at an average of 344 days. In patients outside UCSF, tumor recurrence was equivalent to Milan and UCSF criteria recipients who waited9 months from LRT. Although tumor recurrence was more likely in outside of UCSF patients (3% versus 9% versus 15%; P = 0.02), recurrence-free survival only trended toward significance among the groups (P = 0.053).Selective patients outside of traditional size criteria can be effectively transplanted with equivalent survival to patients with smaller tumors, even when pathologic tumor burden is considered. Tumor stability over time can be used to help select patients for transplantation.
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- 2020
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12. Early humoral immune response to two doses of severe acute respiratory syndrome coronavirus 2 vaccine in a diverse group of solid organ transplant candidates and recipients
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Howard J. Huang, Stephanie G. Yi, Constance M. Mobley, Ashish Saharia, Arvind Bhimaraj, Linda W. Moore, Malgorzata Kloc, Horacio E. Adrogue, Edward A. Graviss, Duc T. Nguyen, Todd N. Eagar, Stephen L. Jones, Victor Ankoma‐Sey, Thomas E. MacGillivray, Richard J. Knight, A. Osama Gaber, and R. Mark Ghobrial
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Transplantation ,COVID-19 Vaccines ,SARS-CoV-2 ,Immunoglobulin G ,COVID-19 ,Humans ,Organ Transplantation ,RNA, Messenger ,Antibodies, Viral ,BNT162 Vaccine ,Transplant Recipients ,Aged ,Immunity, Humoral - Abstract
Response to two doses of a nucleoside-modified messenger ribonucleic acid (mRNA) vaccine was evaluated in a large solid-organ transplant program. mRNA COVID-19 vaccine was administered to transplant candidates and recipients who met study inclusion criteria. Qualitative anti-SARS-CoV-2 Spike Total Immunoglobulin (Ig) and IgG-specific assays, and a semi-quantitative test for anti-SARS-CoV-2 Spike protein IgG were measured in 241 (17.2%) transplant candidates and 1163 (82.8%) transplant recipients; 55.2% of whom were non-Hispanic White and 44.8% identified as another race. Transplant recipients were a median (IQR) of 3.2 (1.1, 6.8) years from transplantation. Response differed by transplant status: 96.0% versus 43.2% by the anti-SARS-CoV-2 Total Ig (candidates vs. recipients, respectively), 93.5% versus 11.6% by the anti-SARS-CoV-2 IgG assay, and 91.9% versus 30.1% by anti-spike titers after two doses of vaccine. Multivariable analysis revealed candidates had higher likelihood of response versus recipients (odds ratio [OR], 14.6; 95 %CI 2.19, 98.11; P = .02). A slightly lower response was demonstrated in older patients (OR .96; 95 %CI .94, .99; P = .002), patients taking antimetabolites (OR, .21; 95% CI .08, .51; P = .001). Vaccination prior to transplantation should be encouraged.
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- 2022
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13. Successful Double DIEP Syngeneic Transplantation across Monozygotic Twins for Total Back Reconstruction
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Lionel Kameni, Charles E. Butler, Carrie K. Chu, Alex F. Mericli, Osama Gaber, Jesse C. Selber, Keila Torres, Mark Schaverien, and Rene D. Largo
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medicine.medical_specialty ,Skin Neoplasms ,medicine.medical_treatment ,Surgical Wound ,Vascularized Composite Allotransplantation ,Laparotomy ,medicine.artery ,medicine ,Humans ,Contraindication ,Back ,business.industry ,Abdominal Wall ,Dermatofibrosarcoma ,Immunosuppression ,Twins, Monozygotic ,Middle Aged ,medicine.disease ,Epigastric Arteries ,Surgery ,Tumor Burden ,Transplantation ,Transplantation, Isogeneic ,Treatment Outcome ,Female ,Sarcoma ,Neoplasm Recurrence, Local ,business ,Perforator Flap ,Lumbar arteries ,Perforator flaps - Abstract
Background A 56-year-old woman presented with an extensive sarcoma requiring nearly total back resection. She had limited donor sites for reconstruction because of a previous laparotomy, but presented with a significantly larger, identical twin. Cancer has traditionally been considered a contraindication for vascularized composite allotransplantation; however, immunosuppression is potentially avoidable between monozygotic twins. Methods A preoperative genetic workup revealed 10/10 human leukocyte antigen homozygosity. Despite substantial phenotypic divergence in size and facial features, the sisters were genotypically identical. A two-stage, double deep inferior epigastric perforator transplant was planned for delayed reconstruction. At the first stage following the resection, an arteriovenous loop was performed to provide recipient vasculature to the back. At a second stage, the transplantation was performed. In addition, bilateral lumbar artery perforator flaps were created to reduce the length of the defect. Intraoperative steroid bolus and a short taper alone were used for immunosuppression. Results The resection resulted in a 22 × 29-cm specimen down to the spine. After a 4-day interval for permanent pathologic evaluation, the transplant was successfully transferred between twins. Two arteries and six veins were anastomosed to establish perfusion. Postoperatively, there have been no episodes of rejection or flap compromise at last follow-up (>36 months). Conclusions This case represents one of the few vascularized composite allotransplantations between monozygotic twins, and the only reported successful vascularized composite allotransplantation for a recurrent cancer diagnosis. Oncologic safety depended on 100 percent histocompatibility to avoid immunosuppression. Limited patient donor sites precluded total autologous coverage, and a substantial size discrepancy between the twins favored a transplant.
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- 2021
14. Successful Kidney Transplantation Is Associated With Weight Gain From Truncal Obesity and Insulin Resistance
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A. Osama Gaber, Roman J. Shypailo, Joy V. Nolte Fong, Linda W. Moore, Biruh Workeneh, and William E. Mitch
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Adult ,Male ,0301 basic medicine ,medicine.medical_specialty ,medicine.medical_treatment ,030232 urology & nephrology ,Medicine (miscellaneous) ,Adipose tissue ,Weight Gain ,03 medical and health sciences ,0302 clinical medicine ,Insulin resistance ,Internal medicine ,Living Donors ,medicine ,Humans ,Obesity ,Prospective Studies ,Prospective cohort study ,Exercise ,Kidney transplantation ,Kidney ,030109 nutrition & dietetics ,Nutrition and Dietetics ,business.industry ,Immunosuppression ,Middle Aged ,medicine.disease ,Kidney Transplantation ,Transplantation ,Treatment Outcome ,medicine.anatomical_structure ,Nephrology ,Body Composition ,Female ,Insulin Resistance ,medicine.symptom ,Energy Metabolism ,business ,Weight gain - Abstract
The objective of this study is to compare changes in body composition, lifestyle factors, and metabolic responses occurring in living kidney transplant recipient patients after transplantation.The study was a single-site, prospective, observational study. To identify metabolic responses during the initial years after transplantation, we obtained state-of-the-art, high-resolution measurements of body composition from a 4-compartment model using dual-energy X-ray absorptiometry, air displacement plethysmography, and total body potassium and nitrogen counters. We also assessed dietary recalls and actigraphy before transplantation and 3- and 12-month after transplantation. The study was conducted at a quaternary care hospital outpatient transplant center and a United States Department of Agriculture Agricultural Research Service center. Thirty-one adults receiving a living donor kidney allograft were studied. The main outcome measures were change in body composition at 3 months and 1 year after transplantation, and this was correlated with the occurrence of insulin resistance.In patients receiving a successful kidney transplant from living donors treated with standard immunosuppression, significant increases in body weight were detected at 3 and 12 months after transplantation (2.2 kg, P = .03 and 6.6 kg, P .0001, respectively). Weight gain was principally due to adipose tissue accumulation in the truncal region. There was no increase in muscle mass or fluid accumulation. Weight gain was not associated with changes in resting energy expenditure or physical activity. Notably, increases in visceral and subcutaneous adipose tissue were positively correlated with insulin resistance.Successful transplantation was associated with increased insulin resistance and weight gain without increases in muscle or fluid. This metabolic pattern suggests potential interventions that could prevent or mitigate the consequences of adipose tissue accumulation in transplant recipients.
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- 2019
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15. A prospective multicenter observational study of cell-mediated immunity as a predictor for cytomegalovirus infection in kidney transplant recipients
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Peter Chin-Hong, Liise K. Kayler, Aneesh K. Mehta, Matthew Cooper, David Wojciechowski, Deepali Kumar, Simon Ball, Camille N. Kotton, Ted Blanchard, James MacDougall, A. Osama Gaber, and Ajit P. Limaye
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Adult ,Male ,medicine.medical_specialty ,T-Lymphocytes ,Enzyme-Linked Immunosorbent Assay ,Kaplan-Meier Estimate ,Antiviral Agents ,Kidney transplant ,Gastroenterology ,Immediate-Early Proteins ,Viral Matrix Proteins ,Young Adult ,Predictive Value of Tests ,Immunity ,Multicenter trial ,Internal medicine ,medicine ,Humans ,Immunology and Allergy ,Pharmacology (medical) ,Interferon gamma ,Prospective Studies ,Aged ,Immunity, Cellular ,Transplantation ,business.industry ,ELISPOT ,virus diseases ,Middle Aged ,Kidney Transplantation ,Cytomegalovirus infection ,Treatment Outcome ,ROC Curve ,Immune System ,Cytomegalovirus Infections ,Kidney Failure, Chronic ,Female ,Observational study ,Peptides ,business ,medicine.drug - Abstract
T cell immunity is essential for the control of cytomegalovirus (CMV) infection after transplantation. We evaluated a CMV-specific peptide-based enzyme-linked immunosorbent spot (ELISPOT) assay to determine whether assay results could predict subsequent CMV events. Adult kidney transplant recipients at 43 centers underwent ELISPOT testing to enumerate interferon gamma (IFN-γ) binding spot-forming units (sfu) after stimulation of cells with an overlapping peptide pool of CMV phosphoprotein 65 (pp65) and immediate early-1 (IE-1) protein at the end of antiviral prophylaxis (EOP) and various time points thereafter. The primary outcome was a CMV event in the first posttransplant year. In 583 kidney transplant recipients (260 seropositive donor [D+]/seronegative recipient [R-] and 277 R+), CMV events occurred in 44 of 368 eligible patients (11.8%) at a median of 227 days (range 92-360) posttransplant. A cutoff value of >40 sfu/2.5 × 105 cells for either IE-1 or pp65 was derived as a threshold for positivity, with a negative predictive value of >97% for CMV events. CMV events were significantly lower in assay positive vs assay negative patients (3.0% vs 19.5%, P 40 at EOP (P
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- 2019
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16. Variability in endocrine cell identity in patients with chronic pancreatitis undergoing islet autotransplantation
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Christine A. Beamish, Solmaz F. Afshar, Omaima M. Sabek, A. Osama Gaber, Dale J. Hamilton, and Daniel W. Fraga
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Adult ,Male ,endocrine system ,medicine.medical_specialty ,medicine.medical_treatment ,Islets of Langerhans Transplantation ,030209 endocrinology & metabolism ,Type 2 diabetes ,030230 surgery ,Transplantation, Autologous ,Islets of Langerhans ,Young Adult ,03 medical and health sciences ,0302 clinical medicine ,Insulin resistance ,Pancreatitis, Chronic ,Internal medicine ,Diabetes mellitus ,medicine ,Humans ,Immunology and Allergy ,Pharmacology (medical) ,Transplantation ,geography ,geography.geographical_feature_category ,business.industry ,Insulin ,Middle Aged ,Prognosis ,medicine.disease ,Islet ,Endocrinology ,medicine.anatomical_structure ,Pancreatectomy ,Pancreatitis ,Female ,Endocrine Cells ,Pancreas ,business ,Biomarkers - Abstract
Beta-cell dedifferentiation as shown by cellular colocalization of insulin with glucagon and/or vimentin, and decreased expression of MAFA and/or urocortin3 has been suggested to contribute to metabolic decompensation in type 2 diabetes, and was recently described postimplantation in islet allotransplant patients. Dysglycaemia and diabetes mellitus are often encountered preoperatively in patients undergoing pancreatectomy and islet autotransplantation (PIAT). In this series of case reports, we document variation in islet phenotypic identity in three patients with chronic pancreatitis (CP) without diabetes or significant insulin resistance who subsequently underwent PIAT. Pancreas histology was examined using colocalization of endocrine hormones, mesenchymal and pan-endocrine markers in islets, and the relative expression of MAFA and urocortin3 in insulin-expressing cells as compared to that of nondiabetic and type 2 diabetic donors. We present results of pre- and posttransplant clinical metabolic testing. Varying degrees of islet-cell dedifferentiation are identified in nondiabetic patients with CP at the time of PIAT, and may need further investigation.
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- 2019
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17. Persistent Immunogenicity of the mRNA COVID-19 Vaccine in Patients Vaccinated Before Kidney Transplant
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Howard J. Huang, Hemangshu Podder, A. Osama Gaber, Richard J. Knight, Linda W. Moore, Robert McMillan, Mark J. Hobeika, R. Mark Ghobrial, Stephanie G. Yi, Hassan N. Ibrahim, and Todd N. Eagar
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Adult ,Transplantation ,2019-20 coronavirus outbreak ,Messenger RNA ,Vaccines, Synthetic ,COVID-19 Vaccines ,Coronavirus disease 2019 (COVID-19) ,business.industry ,SARS-CoV-2 ,Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) ,Immunogenicity ,Vaccination ,COVID-19 ,Middle Aged ,Antibodies, Viral ,Kidney transplant ,Virology ,Kidney Transplantation ,Medicine ,Humans ,In patient ,business ,Letter to the Editor - Published
- 2021
18. Pre-transplant T-cell Clonality: An Observational Study of a Biomarker for Prediction of Sepsis in Liver Transplant Recipients
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Linda W. Moore, Mark J. Hobeika, Xian Chang Li, A. Osama Gaber, Joy V. Nolte Fong, Ashish Saharia, Duc T. Nguyen, David W. Victor, Edward A. Graviss, Constance M. Mobley, Stephen L. Jones, R. Mark Ghobrial, Paul A. Fields, Laurie J. Minze, and Robert McMillan
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Male ,Prognostic variable ,medicine.medical_specialty ,Multivariate analysis ,T cell ,Receptors, Antigen, T-Cell ,Sepsis ,Predictive Value of Tests ,Internal medicine ,medicine ,Humans ,Cause of death ,Aged ,business.industry ,Middle Aged ,medicine.disease ,Liver Transplantation ,Transplantation ,medicine.anatomical_structure ,Preoperative Period ,Biomarker (medicine) ,Surgery ,Observational study ,Female ,Clonal Hematopoiesis ,business ,Biomarkers - Abstract
OBJECTIVE This study investigated the ability of pre-transplant T-cell clonality to predict sepsis after liver transplant (LT). SUMMARY BACKGROUND DATA Sepsis is a leading cause of death in LT recipients. Currently, no biomarkers predict sepsis before clinical symptom manifestation. METHODS Between December 2013 and March 2018, our institution performed 478 LTs. After exclusions (eg, patients with marginal donor livers, autoimmune disorders, nonabdominal multi-organ, and liver retransplantations), 180 consecutive LT were enrolled. T-cell characterization was assessed within 48 hours before LT (immunoSEQ Assay, Adaptive Biotechnologies, Seattle, WA). Sepsis-2 and Sepsis-3 cases, defined by presence of acute infection plus ≥2 SIRS criteria, or clinical documentation of sepsis, were identified by chart review. Receiver-operating characteristic analyses determined optimal T-cell repertoire clonality for predicting post-LT sepsis. Kaplan-Meier and Cox proportional hazard modeling assessed outcome-associated prognostic variables. RESULTS Patients with baseline T-cell repertoire clonality ≥0.072 were 3.82 (1.25, 11.40; P = 0.02), and 2.40 (1.00, 5.75; P = 0.049) times more likely to develop sepsis 3 and 12 months post-LT, respectively, when compared to recipients with lower (
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- 2021
19. Effectiveness of Bariatric Surgery in Increasing Kidney Transplant Eligibility in Patients with Kidney Failure Requiring Dialysis
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Basem G, Soliman, Nabil, Tariq, Yi Ying, Law, Stephanie, Yi, Nwabunie, Nwana, Rita, Bosetti, Bita, Kash, Linda W, Moore, A Osama, Gaber, and Vadim, Sherman
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Gastric Bypass ,Bariatric Surgery ,Middle Aged ,Kidney Transplantation ,Obesity, Morbid ,Postoperative Complications ,Treatment Outcome ,Gastrectomy ,Renal Dialysis ,Humans ,Female ,Laparoscopy ,Renal Insufficiency ,Retrospective Studies - Abstract
Severe obesity can increase risk of complications after kidney transplantation. There is a paucity of literature on bariatric surgery outcomes in renal transplant candidates. The objective of this study was to analyze outcomes of bariatric surgery as a weight reduction strategy for patients with kidney failure to enhance eligibility for kidney transplantation.We performed a retrospective analysis of the Metabolic and Bariatric Surgery Accreditation and Quality Improvement Program database at a single institution for patients with chronic kidney disease receiving hemodialysis therapy (CKD G5D) undergoing bariatric surgery between 2011 and 2018.Of 2363 patients who underwent bariatric surgery, 38 (1.6%) had CKD G5D; median age (range) was 49 years (33; 69), 52.6% were female, and mean BMI was 44.2 kg/mLaparoscopic bariatric surgery offers effective weight loss for CKD G5D patients to achieve transplant eligibility with acceptable outcomes.
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- 2021
20. First World Consensus Conference on Pancreas Transplantation: Part II - recommendations
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Jonathan A. Fridell, Gabriel C. Oniscu, Marcelo Perosa, Quirino Lai, Helmut Arbogast, Jean-Paul Squifflet, Paola Maffi, Axel Andres, Jose Oberholzer, Claudio Ricci, Eelco J.P. de Koning, Daniel Casanova, Osama Gaber, Stephen T. Bartlett, Giuseppe Orlando, Ugo Boggi, Peter Schenker, Giuseppe Maria Ettorre, Piero Marchetti, R. Paul Robertson, Jenny E. Gunton, Steven A. White, Sara Iacopi, Raja Kandaswamy, Robert Öllinger, Pablo Uva, Francesco Menichetti, Rainer W.G. Gruessner, Dixon B. Kaufman, Lainie Friedman Ross, Cinthia B. Drachenberg, Paolo Rigotti, Robert R. Redfield, José Davide, Joseph R. Scalea, Mario Miccoli, Fanny Buron, Chiara Terrenzio, Duck Jong Han, Vittorio Perrone, Henry Pleass, Laureano Fernandez Cruz, Hussein A. Khambalia, Walter Baronti, Lucrezia Furian, Thierry Berney, Donzilia Sousa Silva, Robert Langer, Emmanuel Morelon, Peter G. Stock, Niccolò Napoli, Peter J. Friend, Robert J. Stratta, Fabio Vistoli, Matthew Cooper, Massimo Cardillo, Shruti Mittal, Frantisek Saudek, Adamasco Cupisti, Federica Cipriani, Emanuele Federico Kauffmann, Lionel Badet, Monica Ortenzi, Massimo Rossi, Lorella Marselli, Christopher J.E. Watson, Enrico Benedetti, George W. Burke, Jon S. Odorico, Carlo Socci, Rossana Caldara, Julien Branchereau, Angelika C. Gruessner, Antonio Secchi, Flavia Neri, Takashi Kenmochi, Boggi, Ugo, Vistoli, Fabio, Andres, Axel, Arbogast, Helmut, Badet, Lionel, Baronti, Walter, Bartlett, Stephen T, Benedetti, Enrico, Branchereau, Julien, W Rd Burke, George, Buron, Fanny, Caldara, Rossana, Cardillo, Massimo, Casanova, Daniel, Cipriani, Federica, Cooper, Matthew, Cupisti, Adamasco, Davide, Josè, Drachenberg, Cinthia, de Koning, Eelco Jp, Ettorre, Giuseppe Maria, Fernandez Cruz, Laureano, Fridell, Jonathan, Friend, Peter J, Furian, Lucrezia, Gaber, Osama, Gruessner, Angelika C, Gruessner, Rainer W, Gunton, Jenny, Han, Duck Jong, Iacopi, Sara, Kauffmann, Emanuele Federico, Kaufman, Dixon, Kenmochi, Takashi, Khambalia, Hussein A, Lai, Quirino, Langer, Robert M, Maffi, Paola, Marselli, Lorella, Menichetti, Francesco, Miccoli, Mario, Mittal, Shruti, Morelon, Emmanuel, Napoli, Niccolò, Neri, Flavia, Oberholzer, Jose, Odorico, Jon, Öllinger, Robert, Oniscu, Gabriel, Orlando, Giuseppe, Ortenzi, Monica, Perosa, Marcelo, Perrone, Vittorio Grazio, Pleass, Henry, Redfield, Robert R, Ricci, Claudio, Rigotti, Paolo, Robertson, Paul R, Ross, Lainie, Rossi, Massimo, Saudek, Frantisek, Scalea, Joseph, Schenker, Peter, Secchi, Antonio, Socci, Carlo, Sousa Silva, Donzilia, Squifflet, Jean Paul, Stock, Peter, Stratta, Robert, Terrenzio, Chiara, Uva, Pablo, Watson, Christopher, White, Steven A, Marchetti, Piero, Kandaswamy, Raja, Berney, Thierry, Boggi, Ugo [0000-0002-7505-5896], Vistoli, Fabio [0000-0003-2115-4191], Andres, Axel [0000-0003-3329-0801], Arbogast, Helmut P [0000-0001-5410-8699], Badet, Lionel [0000-0002-9596-0279], Baronti, Walter [0000-0002-4532-3028], Bartlett, Stephen T [0000-0002-3980-2559], Benedetti, Enrico [0000-0003-1120-6058], Branchereau, Julien [0000-0002-8460-9352], Burke, George W [0000-0002-6888-2842], Buron, Fanny [0000-0003-0404-6746], Caldara, Rossana [0000-0001-7115-5681], Cardillo, Massimo [0000-0002-2776-2297], Casanova, Daniel [0000-0003-3863-5039], Cipriani, Federica [0000-0002-8651-5982], Cooper, Matthew [0000-0002-3438-9638], Cupisti, Adamasco [0000-0002-8995-936X], Davide, Josè [0000-0003-3174-2456], Drachenberg, Cinthia [0000-0002-3104-5661], de Koning, Eelco JP [0000-0002-1232-7022], Ettorre, Giuseppe Maria [0000-0002-7501-5472], Fernandez Cruz, Laureano [0000-0001-5652-1209], Fridell, Jonathan A [0000-0002-8708-1506], Friend, Peter J [0000-0003-0841-9685], Furian, Lucrezia [0000-0002-2264-7986], Gaber, Osama A [0000-0002-9444-3202], Gruessner, Angelika C [0000-0001-5961-5913], Gruessner, Rainer WG [0000-0002-2094-9817], Gunton, Jenny E [0000-0002-8127-9773], Han, Duck-Jong [0000-0002-0990-6824], Kauffmann, Emanuele Federico [0000-0001-7634-4844], Kaufman, Dixon [0000-0003-3615-0994], Kenmochi, Takashi [0000-0002-9090-8770], Khambalia, Hussein A [0000-0002-7553-3026], Lai, Quirino [0000-0003-1487-3235], Langer, Robert M [0000-0001-8349-1260], Maffi, Paola [0000-0001-5011-6499], Marselli, Lorella [0000-0002-6698-2962], Menichetti, Francesco [0000-0003-0824-7166], Miccoli, Mario [0000-0002-8632-6145], Mittal, Shruti [0000-0003-2390-5366], Morelon, Emmanuel [0000-0001-9928-1671], Napoli, Niccolò [0000-0003-2538-9158], Neri, Flavia [0000-0002-2677-8967], Oberholzer, Jose [0000-0002-1069-2501], Odorico, Jon S [0000-0003-1096-464X], Öllinger, Robert [0000-0002-4499-1673], Oniscu, Gabriel [0000-0003-1714-920X], Orlando, Giuseppe [0000-0002-6460-7974], Ortenzi, Monica [0000-0002-6508-6488], Perosa, Marcelo [0000-0002-8576-9761], Pleass, Henry [0000-0002-9814-0452], Redfield, Robert R [0000-0001-5986-3466], Ricci, Claudio [0000-0002-6638-4479], Rigotti, Paolo [0000-0002-8895-935X], Ross, Lainie F [0000-0002-7395-3000], Rossi, Massimo [0000-0001-5105-4656], Saudek, Frantisek [0000-0002-0448-4351], Scalea, Joseph R [0000-0001-8278-2859], Schenker, Peter [0000-0002-3607-6993], Secchi, Antonio [0000-0002-4208-5116], Socci, Carlo [0000-0002-3276-5556], Sousa Silva, Donzilia [0000-0002-7165-3581], Squifflet, Jean Paul [0000-0002-0467-7559], Stock, Peter G [0000-0002-5806-0167], Stratta, Robert J [0000-0001-7634-094X], Terrenzio, Chiara [0000-0002-0629-2134], Uva, Pablo [0000-0001-7317-3875], Watson, Christopher JE [0000-0002-0590-4901], Marchetti, Piero [0000-0003-4907-0635], Kandaswamy, Raja [0000-0003-4302-0119], Berney, Thierry [0000-0002-4230-9378], Apollo - University of Cambridge Repository, Boggi U., Vistoli F., Andres A., Arbogast H.P., Badet L., Baronti W., Bartlett S.T., Benedetti E., Branchereau J., Burke G.W., Buron F., Caldara R., Cardillo M., Casanova D., Cipriani F., Cooper M., Cupisti A., Davide J., Drachenberg C., de Koning E.J.P., Ettorre G.M., Fernandez Cruz L., Fridell J.A., Friend P.J., Furian L., Gaber O.A., Gruessner A.C., Gruessner R.W.G., Gunton J.E., Han D.-J., Iacopi S., Kauffmann E.F., Kaufman D., Kenmochi T., Khambalia H.A., Lai Q., Langer R.M., Maffi P., Marselli L., Menichetti F., Miccoli M., Mittal S., Morelon E., Napoli N., Neri F., Oberholzer J., Odorico J.S., Ollinger R., Oniscu G., Orlando G., Ortenzi M., Perosa M., Perrone V.G., Pleass H., Redfield R.R., Ricci C., Rigotti P., Paul Robertson R., Ross L.F., Rossi M., Saudek F., Scalea J.R., Schenker P., Secchi A., Socci C., Sousa Silva D., Squifflet J.P., Stock P.G., Stratta R.J., Terrenzio C., Uva P., Watson C.J.E., White S.A., Marchetti P., Kandaswamy R., and Berney T.
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medicine.medical_specialty ,medicine.medical_treatment ,Pancreas transplantation ,clinical research/practice ,Pancreas/simultaneous pancreas-kidney transplantation ,Quality of life ,Renal Dialysi ,Renal Dialysis ,Diabetes mellitus ,medicine ,Risk of mortality ,Humans ,Immunology and Allergy ,survey ,Pharmacology (medical) ,Survey ,Intensive care medicine ,Dialysis ,Kidney transplantation ,pancreas/simultaneous pancreas‐kidney transplantation ,Transplantation ,ddc:617 ,diabetes ,pancreas/simultaneous pancreas-kidney transplantation ,business.industry ,Diabetes ,Graft Survival ,medicine.disease ,Kidney Transplantation ,Diabetes Mellitus, Type 1 ,surgical procedures, operative ,diabete ,Clinical research/practice ,Quality of Life ,Life expectancy ,Special Articles ,Original Article ,Pancreas Transplantation ,business ,Human - Abstract
Funder: Fondazione Pisa, Pisa, Italy; Id: http://dx.doi.org/10.13039/100007368, Funder: Tuscany Region, Italy; Id: http://dx.doi.org/10.13039/501100009888, Funder: Pisa University Hospital, Pisa, Italy, Funder: University of Pisa, Pisa, Italy; Id: http://dx.doi.org/10.13039/501100007514, The First World Consensus Conference on Pancreas Transplantation provided 49 jury deliberations regarding the impact of pancreas transplantation on the treatment of diabetic patients, and 110 experts' recommendations for the practice of pancreas transplantation. The main message from this consensus conference is that both simultaneous pancreas-kidney transplantation (SPK) and pancreas transplantation alone can improve long-term patient survival, and all types of pancreas transplantation dramatically improve the quality of life of recipients. Pancreas transplantation may also improve the course of chronic complications of diabetes, depending on their severity. Therefore, the advantages of pancreas transplantation appear to clearly surpass potential disadvantages. Pancreas after kidney transplantation increases the risk of mortality only in the early period after transplantation, but is associated with improved life expectancy thereafter. Additionally, preemptive SPK, when compared to SPK performed in patients undergoing dialysis, appears to be associated with improved outcomes. Time on dialysis has negative prognostic implications in SPK recipients. Increased long-term survival, improvement in the course of diabetic complications, and amelioration of quality of life justify preferential allocation of kidney grafts to SPK recipients. Audience discussions and live voting are available online at the following URL address: http://mediaeventi.unipi.it/category/1st-world-consensus-conference-of-pancreas-transplantation/246.
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- 2021
21. Long-Term Follow-Up of Renal Transplant Recipients Treated With IVIG for De Novo Donor-Specific Antibodies
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Duc T. Nguyen, Richard J. Knight, A. Osama Gaber, Jennifer Loucks-Devos, Samir J. Patel, Naja A. Khan, Todd N. Eagar, and Edward A. Graviss
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Graft Rejection ,medicine.medical_specialty ,Long term follow up ,Gastroenterology ,Interquartile range ,HLA Antigens ,Isoantibodies ,hemic and lymphatic diseases ,Internal medicine ,Medicine ,Humans ,Dosing ,Retrospective Studies ,Transplantation ,business.industry ,Donor specific antibodies ,Graft Survival ,Immunoglobulins, Intravenous ,Kidney Transplantation ,Transplant Recipients ,Renal transplant ,Cohort ,Renal allograft ,Stable function ,Surgery ,business ,Follow-Up Studies - Abstract
Background Renal allograft survival is negatively affected by the development of de novo posttransplant donor-specific antibodies (dnDSA). We sought to determine whether treatment with intravenous immunoglobulin (IVIG) could remove or reduce the intensity of dnDSA. Methods A single-center study of 12 recipients with dnDSA and stable function who received IVIG 1 g/kg monthly for 6 months were compared with a contemporaneous cohort of 24 recipients with dnDSA who did not receive IVIG. Results The median time to first dnDSA was 6 months (interquartile range [IQR], 1-12), and follow-up was 83 months (IQR, 58-94) posttransplant. Resolution of dnDSA occurred in 27% of IVIG vs 46% of control recipients (P = .48). Fifty-eight percent of recipients in both cohorts demonstrated a reduction in the intensity of the dominant DSA at last follow-up (P =1.0). A reduction in the number of dnDSAs occurred in 58% vs 62% of the IVIG and control cohorts, respectively (P = .81). Post-dnDSA, acute rejection occurred in 8% of the IVIG vs 42% in the control group (P = .06). Forty-two percent of IVIG-treated vs 49% of control recipients had a deterioration in function from first dnDSA until most recent follow-up (P = .81). Actuarial graft survivals were equivalent between groups. Conclusions IVIG treatment of dnDSA in recipients with stable graft function had no impact on DSA clearance or MFI reduction, but this outcome may also be owing to sample size. Larger studies or alternate dosing regimens may be required to determine if there is any role for the use of IVIG as a treatment for dnDSA.
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- 2020
22. Alpha-Fetoprotein as a Modifier of Anatomic Criteria for Transplantation of HCC Patients
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Larry D. Teeter, Amany Sholkamy, Mostafa Elshazli, Hatem Ali, Karim M Soliman, Edward A. Graviss, A. Osama Gaber, Ahmed Daoud, and Sherif Mogawer
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Adult ,Male ,medicine.medical_specialty ,Carcinoma, Hepatocellular ,education ,Liver transplants ,Milan criteria ,Gastroenterology ,Severity of Illness Index ,Internal medicine ,medicine ,Humans ,Transplantation ,business.industry ,Patient Selection ,Liver Neoplasms ,Middle Aged ,medicine.disease ,digestive system diseases ,Liver Transplantation ,Survival Rate ,Treatment Outcome ,Hepatocellular carcinoma ,Surgery ,Female ,alpha-Fetoproteins ,business ,Alpha-fetoprotein ,Biomarkers - Abstract
The current listing criteria (Milan, University of California San Francisco [UCSF]) for orthotropic liver transplants (OLT) in hepatocellular carcinoma (HCC) patients emphasize the anatomic features of the tumor such as size, burden, and multiplicity. Recent reports showed that patients with large tumors may have equivalent survival to Milan criteria patients. This suggests that differences in biologic behavior of tumors may contribute to the outcome.The aim of this article is to understand the impact of biologic modifiers such as alpha-fetoprotein (AFP) on survival in both Milan and UCSF HCC patients.We reviewed all liver transplants reported to the United Network for Organ Sharing between 2002 and 2013. We analyzed the survival of patients transplanted for HCC who fit the Milan criteria and those transplanted with tumors beyond Milan and within UCSF criteria. We tested various AFP level cutoffs in both groups in relationship to the 1-, 3-, and 5-year survival rates below and above the proposed cutoffs.Survival difference was significant between Milan patients with AFP ≤ 2500 ng/mL and those with AFP2500 ng/mL (59.1% vs 37.4%; P .001). The mean 5-year survival was 55% for beyond Milan within UCSF patients with AFP ≤ 150 ng/mL and 35.7% for those with AFP150 ng/mL (P = .003).AFP level should be incorporated in the selection criteria for HCC patients considered for OLT. Milan patients with an AFP level exceeding 2500 ng/mL have reduced survival. Patients with tumors beyond Milan and within UCSF criteria whose AFP ≤ 150 ng/mL achieve acceptable 5-year survival and are good candidates for OLT.
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- 2020
23. Early Experience With COVID-19 and Solid Organ Transplantation at a US High-volume Transplant Center
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Arvind Bhimaraj, Mozhgon Moaddab, R. Mark Ghobrial, Kevin Grimes, Stephanie G. Yi, Alex W. Rogers, Ashish Saharia, Maen Abdelrahim, Constance M. Mobley, Richard J. Knight, Howard J. Huang, Romy Faour, Samantha Bullock, Maria Aoun, A. Osama Gaber, Robert McMillan, and Mark J. Hobeika
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Adult ,Male ,medicine.medical_specialty ,medicine.medical_treatment ,Pneumonia, Viral ,Disease ,medicine.disease_cause ,Organ transplantation ,chemistry.chemical_compound ,Betacoronavirus ,Immunocompromised Host ,Tocilizumab ,Internal medicine ,medicine ,Humans ,Pandemics ,Coronavirus ,Aged ,Immunosuppression Therapy ,Transplantation ,business.industry ,SARS-CoV-2 ,COVID-19 ,Hydroxychloroquine ,Immunosuppression ,Organ Transplantation ,Original Clinical Science—General ,Middle Aged ,medicine.disease ,Texas ,Transplant Recipients ,Pneumonia ,Cytokine release syndrome ,Intensive Care Units ,chemistry ,Female ,business ,Coronavirus Infections ,medicine.drug - Abstract
The novel coronavirus SARS-CoV-2 [coronavirus disease 2019 (COVID-19)] is a highly contagious and devastating virus that has currently infected over 2.5 million people worldwide and resulted in 177 641 deaths as of April 2020.1 Although most people diagnosed with COVID-19 exhibit mild-to-moderate symptoms, early reports from China described vulnerable patient populations, such as the elderly and those with chronic underlying medical conditions including the immunosuppressed, having more severe COVID-19-related illness compared to the general population.2,3 Solid organ transplant (SOT) recipients are one of the largest cohorts of immunosuppressed patients, yet little is known about their risk of contracting the virus, postinfection outcomes, and effect of immunosuppression on the clinical course of the disease. Unique challenges, such as immunosuppression management and interpretation of laboratory data, also exist. Current treatment strategies borrow upon prior experience from other pandemics, such as severe acute respiratory syndrome (SARS) and influenza A virus subtype.4 SARS-CoV-2 primarily affects the respiratory tract, progressing from pneumonia to acute respiratory distress syndrome in severe cases.5 In these cases, there is a recognized cytokine release syndrome (CRS) that when occurs results in multiorgan dysfunction and failure.6 The role of immunosuppression in mounting such inflammatory response is unclear. Inflammatory markers, such as C-reactive protein (CRP), lactate dehydrogenase (LDH), and D-dimer, may reflect disease progression and/or severity.7 Lymphopenia is reported as a common presentation among COVID-19 positive patients.8,9 Treatment options are limited. Antivirals such as hydroxychloroquine (HCQ) with or without azithromycin are widely used empiric options. Remdesivir, an RNA polymerase inhibitor, has shown in vitro activity against SARS-CoV-2 and is currently under phase 3 trial.10 Investigational agents to combat the cytokine response, such as tocilizumab, an interleukin 6 (IL-6) receptor inhibitor, are being studied. Although the exact role of immunosuppression on the progression of COVID-19 is unknown, early case reports of kidney transplant recipients suggest minimizing immunosuppression while continuing steroidal therapy.11 Evaluation of clinical symptoms, utility of biomarkers, and progression of disease are important to understand for optimizing the management in COVID-19 positive SOT recipients. The effect of COVID-19 on the heart, lung, liver, pancreas, and kidney transplant organ systems is not well described. Herein, we present our experience with 21 consecutive SOT recipients diagnosed with COVID-19 at the Houston Methodist J.C. Walter Transplant Center followed to April 22, 2020.
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- 2020
24. Novel Silicon Titanium Diboride Micropatterned Substrates for Cellular Patterning
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W. Zagozdzon-Wosik, Jefferson Friguglietti, Omaima M. Sabek, Phi Le, Daniel W. Fraga, Jianhua Gu, Lewis Francis, Darius McPhail, Fatima A. Merchant, A. Osama Gaber, Marcos Quintela, Salvatore A. Gazze, and Susmi Das
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Boron Compounds ,Silicon ,Materials science ,Biophysics ,Bioengineering ,Nanotechnology ,02 engineering and technology ,Soft lithography ,law.invention ,Biomaterials ,03 medical and health sciences ,chemistry.chemical_compound ,law ,Cell Adhesion ,Humans ,Surface charge ,030304 developmental biology ,Titanium ,0303 health sciences ,Durotaxis ,Cell growth ,Mesenchymal Stem Cells ,021001 nanoscience & nanotechnology ,chemistry ,Mechanics of Materials ,Cell culture ,Ceramics and Composites ,Surface modification ,Photolithography ,0210 nano-technology ,Titanium diboride - Abstract
Both hard material photolithography and soft lithography are widely used for patterned cell culture. Soft lithography techniques enable bioactive molecule incorporation, however complex surface modifications are required to introduce specific ligands or proteins in conventional photolithography. In this study, we demonstrate human umbilical vein cell (HUVEC) and adult bone marrow derived mesenchymal stem cell (MSC) patterning on titanium diboride (TiB2) layers deposited on silicon (Si) substrates by electron-beam evaporation and micropatterned using photolithography. Micropatterned cell growth specificity on geometric shapes of circle and/or lines is achieved via differential growth factors adsorption in the presence of heparin. Specifically, the deposited films of TiB2 showed increased stiffness, hardness, hydrophilicity and surface charge when compared to background Si. These substrates were found to be compatible with HUVEC and MSC viability, based on biomarker expression and RNA-sequence transcriptome analysis. Cell-type dependent, micropattern selective cell growth, such as contact guidance, alignment, and durotaxis, were observed. In addition, MSC clustering was achieved, enabling a three-dimensional (3D) aggregate based microenvironment during culture. This study clearly demonstrates the potential of microfabricated Si and TiB2 biomaterials for patterned cell culture in vitro, independent of any additional surface modification.
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- 2020
25. The Incremental Cost of Incompatible Living Donor Kidney Transplantation: A National Cohort Analysis
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Bashir R. Sankari, Marc P. Posner, Lloyd E. Ratner, Ron Shapiro, Jason R. Wellen, Adel Bozorgzadeh, David A. Gerber, Krista L. Lentine, A. Osama Gaber, Ty B. Dunn, Huiling Xiao, Debra L. Sudan, Christopher L. Marsh, George S. Lipkowitz, Jose Oberholzer, Marc L. Melcher, Xun Luo, John P. Roberts, Sandip Kapur, Matthew Cooper, Stanley C. Jordan, Jose M. El-Amm, Robert A. Montgomery, Jacqueline Garonzik-Wang, Pooja Singh, Dorry L. Segev, Ronald P. Pelletier, Babak J. Orandi, Mark A. Schnitzler, Michael A. Rees, Allan B. Massie, Paul W. Nelson, Mark D. Stegall, and David A. Axelrod
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Graft Rejection ,Male ,Marginal cost ,medicine.medical_specialty ,030232 urology & nephrology ,030230 surgery ,Kidney Function Tests ,Living donor ,National cohort ,03 medical and health sciences ,Postoperative Complications ,0302 clinical medicine ,Risk Factors ,Internal medicine ,Living Donors ,Humans ,Immunology and Allergy ,Medicine ,Pharmacology (medical) ,health care economics and organizations ,Kidney transplantation ,Retrospective Studies ,Transplantation ,biology ,business.industry ,Flow cytometric crossmatch ,Histocompatibility Testing ,Graft Survival ,Antibody titer ,Middle Aged ,Prognosis ,medicine.disease ,Kidney Transplantation ,Surgery ,Blood Group Incompatibility ,Case-Control Studies ,Quality of Life ,biology.protein ,Kidney Failure, Chronic ,Female ,Antibody ,business ,Follow-Up Studies ,Glomerular Filtration Rate - Abstract
Incompatible living donor kidney transplantation (ILDKT) has been established as an effective option for end-stage renal disease patients with willing but HLA-incompatible living donors, reducing mortality and improving quality of life. Depending on antibody titer, ILDKT can require highly resource-intensive procedures, including intravenous immunoglobulin, plasma exchange, and/or cell-depleting antibody treatment, as well as protocol biopsies and donor-specific antibody testing. This study sought to compare the cost and Medicare reimbursement, exclusive of organ acquisition payment, for ILDKT (n = 926) with varying antibody titers to matched compatible transplants (n = 2762) performed between 2002 and 2011. Data were assembled from a national cohort study of ILDKT and a unique data set linking hospital cost accounting data and Medicare claims. ILDKT was more expensive than matched compatible transplantation, ranging from 20% higher adjusted costs for positive on Luminex assay but negative flow cytometric crossmatch, 26% higher for positive flow cytometric crossmatch but negative cytotoxic crossmatch, and 39% higher for positive cytotoxic crossmatch (p
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- 2017
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26. Induction of IAPP amyloid deposition and associated diabetic abnormalities by a prion-like mechanism
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Diego Morales-Scheihing, Mohammad Shahnawaz, A. Osama Gaber, Claudio Soto, Cesar Gonzalez, Ines Moreno-Gonzalez, Abhisek Mukherjee, Daniel W. Fraga, Nicolas Mendez, Natalia Salvadores, Omaima M. Sabek, and Kathleen Taylor-Presse
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0301 basic medicine ,Genetically modified mouse ,Male ,medicine.medical_specialty ,endocrine system ,endocrine system diseases ,Amyloid ,Prions ,Immunology ,Endogeny ,Mice, Transgenic ,Protein aggregation ,Article ,03 medical and health sciences ,Islets of Langerhans ,Mice ,Protein Aggregates ,0302 clinical medicine ,In vivo ,Internal medicine ,medicine ,Immunology and Allergy ,Animals ,Humans ,Proteostasis Deficiencies ,Research Articles ,geography ,geography.geographical_feature_category ,biology ,Chemistry ,Islet ,In vitro ,Islet Amyloid Polypeptide ,030104 developmental biology ,Endocrinology ,Diabetes Mellitus, Type 2 ,biology.protein ,Female ,Antibody ,030217 neurology & neurosurgery - Abstract
In this article, Mukherjee et al. show that the pathologic and clinical alterations of type 2 diabetes can be induced in vitro and in vivo by prion-like transmission of IAPP misfolded aggregates, supporting an important role for IAPP aggregation in the disease., Although a large proportion of patients with type 2 diabetes (T2D) accumulate misfolded aggregates composed of the islet amyloid polypeptide (IAPP), its role in the disease is unknown. Here, we show that pancreatic IAPP aggregates can promote the misfolding and aggregation of endogenous IAPP in islet cultures obtained from transgenic mouse or healthy human pancreas. Islet homogenates immunodepleted with anti-IAPP–specific antibodies were not able to induce IAPP aggregation. Importantly, intraperitoneal inoculation of pancreatic homogenates containing IAPP aggregates into transgenic mice expressing human IAPP dramatically accelerates IAPP amyloid deposition, which was accompanied by clinical abnormalities typical of T2D, including hyperglycemia, impaired glucose tolerance, and a substantial reduction on β cell number and mass. Finally, induction of IAPP deposition and diabetic abnormalities were also induced in vivo by administration of IAPP aggregates prepared in vitro using pure, synthetic IAPP. Our findings suggest that some of the pathologic and clinical alterations of T2D might be transmissible through a similar mechanism by which prions propagate in prion diseases.
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- 2017
27. Outcomes of kidney transplantation using deceased donors with history of diabetes
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Edward A. Graviss, Faiza N Khan, Duc T. Nguyen, A. Osama Gaber, Wadi N. Suki, Luan D. Truong, Adaani E. Frost, and Muhammad I Bhatti
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medicine.medical_specialty ,030230 surgery ,Kidney ,Gastroenterology ,Diabetic nephropathy ,03 medical and health sciences ,0302 clinical medicine ,Diabetes mellitus ,Internal medicine ,medicine ,Diabetes Mellitus ,Humans ,Kidney transplantation ,Transplantation ,Deceased donor ,business.industry ,Graft Survival ,Donor status ,medicine.disease ,Kidney Transplantation ,Tissue Donors ,Treatment Outcome ,Cohort ,030211 gastroenterology & hepatology ,business ,Normal kidneys - Abstract
Deceased diabetic kidneys are increasingly utilized in transplantation. The relationship of donor's history of diabetes to clinical and histological outcomes was examined. Forty-nine diabetic deceased donor kidneys (D-DM) were transplanted into 26 normal (R-N/D-DM) and 23 diabetic recipients (R-DM/D-DM) and compared to 211 diabetic recipients of normal kidneys(R-DM/D-N) and 466 normal recipients of normal kidneys (R-N/D-N). Patient survival at 5 years was 89.7% in R-N/D-N, 96.2% in R-N/D-DM, 80.1% in R-DM/D-N, and a 71.6% in R-DM/D-DM (P = .008). Death-censored graft survival at 5 years was 86.3% in R-N/D-N, 87.4% in R-N/D-DM, 93.5% in R-DM/D-N, and 87.5% in R-DM/D-DM (P = .24). Multivariable regression analysis showed that compared to non-diabetic recipients, diabetic recipients had a 2- to 3-fold increased risk of mortality. In this cohort, there was no impact on death-censored graft survival of diabetic donor status. Only 6 of 26 post-perfusion biopsies showed evidence of diabetic nephropathy (
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- 2019
28. Weight Gain After Simultaneous Kidney and Pancreas Transplantation
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Duc T. Nguyen, A. Islam, Anna Kagan, Hemangshu Podder, Archana R. Sadhu, A. Osama Gaber, Richard J. Knight, Edward A. Graviss, Linda W. Moore, and Christine Pham
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Adult ,Graft Rejection ,Male ,medicine.medical_specialty ,medicine.medical_treatment ,Pancreas transplantation ,Weight Gain ,Gastroenterology ,Interquartile range ,Internal medicine ,Diabetes mellitus ,Medicine ,Humans ,Insulin ,Obesity ,Postoperative Period ,Retrospective Studies ,Glycated Hemoglobin ,Metabolic Syndrome ,Transplantation ,business.industry ,Graft Survival ,Retrospective cohort study ,Immunosuppression ,Middle Aged ,medicine.disease ,Kidney Transplantation ,Diabetes Mellitus, Type 2 ,Female ,Pancreas Transplantation ,medicine.symptom ,Metabolic syndrome ,business ,Weight gain ,Immunosuppressive Agents ,Follow-Up Studies - Abstract
BACKGROUND Excessive weight (EW) gain is common after solid organ transplantation, but there is little information concerning obesity after pancreas transplantation. The study goal was to characterize EW gain after kidney-pancreas (KP) transplantation. METHODS This was a retrospective single-center review of 100 KP recipients transplanted between September 2007 and June 2015. RESULTS The median percent weight gain for all recipients at 1 year posttransplant was 10% (interquartile range, 2.7%-19.3%) of baseline weight. EW gain, defined as greater than or equal to a 19% 1-year increase in weight, included all recipients (n = 26) above the upper limit of interquartile range for weight gain at 1 year. In multivariate analysis, recipient age
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- 2019
29. Cross-sectional evaluation of the relationship between vitamin D status and supplement use across levels of kidney function in adults
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Wadi N. Suki, Keri E. Lunsford, Richard J. Knight, A. Osama Gaber, Omaima M. Sabek, and Linda W. Moore
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Adult ,Male ,Population ,Renal function ,Physiology ,Parathyroid hormone ,030204 cardiovascular system & hematology ,Kidney ,Bone resorption ,03 medical and health sciences ,chemistry.chemical_compound ,Young Adult ,0302 clinical medicine ,Kidney Insufficiencies ,Supplement use ,Vitamin D and neurology ,Medicine ,Humans ,030212 general & internal medicine ,Renal Insufficiency ,Bone Resorption ,Vitamin D ,education ,Aged ,Calcifediol ,education.field_of_study ,business.industry ,Research ,General Medicine ,Middle Aged ,Alkaline Phosphatase ,Nutrition Surveys ,Vitamin D Deficiency ,25-hydroxyvitamin D ,United States ,Diabetes and Endocrinology ,Cross-Sectional Studies ,chemistry ,Parathyroid Hormone ,Dietary Supplements ,Vitamin D Deficiency/diagnosis ,Alkaline phosphatase ,Female ,business ,Biomarkers ,Glomerular Filtration Rate - Abstract
ObjectivesThe objective of this study was to assess vitamin D status of US non-pregnant adults using a standardised assay across 15 mL/min/1.73 m2increments of kidney function, report the use of dietary supplements containing vitamin D and assess relationships between vitamin D and markers of bone resorption.DesignThis study is a cross-sectional evaluation.SettingThe study is from the US National Health and Nutrition Evaluation Survey in 2001–2012.ParticipantsThe participants were non-institutionalised, non-pregnant adults, age ≥20 years.Primary and secondary outcome measuresThe primary outcome measure was serum 25OHD evaluated using liquid chromatography-tandem mass spectroscopy traceable to international reference standards. Secondary outcome measures were use of dietary supplements containing vitamin D and the serum intact parathyroid hormone and bone-specific alkaline phosphatase in a subset of participants.ResultsThe median 25OHD concentration in 27 543 US non-pregnant adults was 25.7 ng/mL (range, 2.2–150.0 ng/mL). Vitamin D supplements were used by 38.0%; mean (SE)=757 (43) international units/day. The range of 25OHD concentration across groups, stratified by kidney function, was 23.0–28.1 ng/mL. The lowest concentration of 25OHD observed was in people with higher kidney function (23.0 ng/mL for estimated glomerular filtration rate >105 mL/min/1.73 m2). Only 24% of people not taking a dietary supplement had a 25OHD concentration >30 ng/mL. Serum intact parathyroid hormone inversely correlated with 25OHD within all kidney function groups. Bone-specific alkaline phosphatase was also negatively associated with 25OHD concentration.ConclusionsThese data indicate that 25OHD concentrations and supplement use may be suboptimal in a significant proportion of the population, across all kidney function levels. The response of bone resorption markers further suggests that 25OHD levels could be improved. Together, these data support a re-evaluation of the 25OHD concentration associated with health in adults.
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- 2019
30. A Double‐Blind, Double‐Dummy, Flexible‐Design Randomized Multicenter Trial: Early Safety of Single‐ Versus Divided‐Dose Rabbit Anti‐Thymocyte Globulin Induction in Renal Transplantation
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Tun Jie, A. Osama Gaber, R. B. Stevens, Lucile E. Wrenshall, Clifford D. Miles, Alan C. Farney, Theodore H. Rigley, and John P. Sandoz
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Adult ,Graft Rejection ,Male ,030230 surgery ,law.invention ,03 medical and health sciences ,0302 clinical medicine ,Randomized controlled trial ,Double-Blind Method ,law ,Multicenter trial ,Clinical endpoint ,Immunology and Allergy ,Medicine ,Animals ,Humans ,Pharmacology (medical) ,Prospective Studies ,Antilymphocyte Serum ,Transplantation ,Thymoglobulin ,business.industry ,Graft Survival ,Original Articles ,Clinical Science ,Middle Aged ,Interim analysis ,Kidney Transplantation ,Anti-thymocyte globulin ,Treatment Outcome ,Tolerability ,Anesthesia ,030211 gastroenterology & hepatology ,Original Article ,Female ,Rabbits ,business ,Immunosuppressive Agents ,Glomerular Filtration Rate - Abstract
A previous nonblinded, randomized, single‐center renal transplantation trial of single‐dose rabbit anti‐thymocyte globulin induction (SD‐rATG) showed improved efficacy compared with conventional divided‐dose (DD‐rATG) administration. The present multicenter, double‐blind/double‐dummy STAT trial (Single dose vs. Traditional Administration of Thymoglobulin) evaluated SD‐rATG versus DD‐rATG induction for noninferiority in early (7‐day) safety and tolerability. Ninety‐five patients (randomized 1:1) received 6 mg/kg SD‐rATG or 1.5 mg/kg/dose DD‐rATG, with tacrolimus‐mycophenolate maintenance immunosuppression. The primary end point was a composite of fever, hypoxia, hypotension, cardiac complications, and delayed graft function. Secondary end points included 12‐month patient survival, graft survival, and rejection. Target enrollment was 165 patients with an interim analysis scheduled after 80 patients. Interim analysis showed primary end point noninferiority of SD‐rATG induction (p = 0.6), and a conditional probability of, A double‐blind, randomized, noninferiority clinical trial finds no early safety or efficacy issues with immunosuppression induction using a single 6 mg/kg dose of rabbit anti‐thymocyte globulin instead of the conventional four 1.5 mg/kg doses across four days.
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- 2016
31. Unexplained Methemoglobinemia in Coronavirus Disease 2019: A Case Report
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Hina Faisal, A. Osama Gaber, and Alexi Bloom
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Male ,medicine.medical_specialty ,Anemia ,Pneumonia, Viral ,Case Report ,Ascorbic Acid ,Corynebacterium ,Antibodies, Monoclonal, Humanized ,Methemoglobinemia ,Gastroenterology ,Antioxidants ,Methemoglobin ,Betacoronavirus ,Hydroxocobalamin ,hemic and lymphatic diseases ,Internal medicine ,Pneumonia, Bacterial ,medicine ,Humans ,Enzyme Inhibitors ,Hypoxia ,Pandemics ,Aged ,Corynebacterium Infections ,SARS-CoV-2 ,business.industry ,Acute kidney injury ,COVID-19 ,General Medicine ,Acute Kidney Injury ,Hypoxia (medical) ,medicine.disease ,Ascorbic acid ,Shock, Septic ,Methylene Blue ,Renal Replacement Therapy ,Red blood cell ,medicine.anatomical_structure ,Hematinics ,Hemoglobin ,medicine.symptom ,Coronavirus Infections ,Cytokine Release Syndrome ,Erythrocyte Transfusion ,Respiratory Insufficiency ,business ,Hydroxychloroquine - Abstract
Methemoglobinemia is a rare disorder of the blood in which there is an increase in methemoglobin, which occurs when hemoglobin is present in the oxidized form. Methemoglobin impairs hemoglobin’s ability to transport oxygen, produces functional anemia, and leads to tissue hypoxia. We report the successful management of a case of refractory hypoxia due to acutely acquired methemoglobinemia in a patient undergoing treatment for coronavirus disease 2019 (COVID-19) pneumonia. The cause of methemoglobinemia in this patient remains unknown. Hypoxia and methemoglobinemia did not respond to methylene blue and required administration of packed red blood cell transfusions.
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- 2020
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32. The importance of drug safety and tolerability in the development of new immunosuppressive therapy for transplant recipients: The Transplant Therapeutics Consortium's position statement
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Mark D. Stegall, Kenneth A. Newell, Vanessa Perez, A. Osama Gaber, Kenneth Troy Somerville, Maria Stoeckl Mattera, Neetu Agashivala, Nicole Spear, Matthew J Everly, Debra L. Sudan, Amy C. Porter, Inish O’Doherty, Randall E. Morris, Roslyn B. Mannon, Klaus Romero, M. Roy First, and Sonya Eremenco
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Drug ,Position statement ,medicine.medical_specialty ,Consensus ,Drug-Related Side Effects and Adverse Reactions ,Maximum Tolerated Dose ,media_common.quotation_subject ,030230 surgery ,Risk Assessment ,Unmet needs ,Food and drug administration ,03 medical and health sciences ,0302 clinical medicine ,medicine ,Immunology and Allergy ,Humans ,Pharmacology (medical) ,Intensive care medicine ,Societies, Medical ,media_common ,Transplantation ,business.industry ,Clinical study design ,Organ Transplantation ,Prognosis ,Transplant Recipients ,Tolerability ,Transplant patient ,Patient Safety ,business ,Immunosuppressive Agents - Abstract
The Transplant Therapeutics Consortium (TTC) is a public-private partnership between the US Food and Drug Administration and the transplantation community including the transplantation societies and members of the biopharmaceutical industry. The TTC was formed to accelerate the process of developing new medical products for transplant patients. The initial goals of this collaboration are the following: (a) To define which aspects of the kidney transplant drug-development process have clear needs for improvement from an industry and regulatory perspective; (b) to define which of the unmet needs in the process could be positively impacted through the development of specific drug-development tools based on available data; and (c) to determine the most appropriate pathway to achieve regulatory acceptance of the proposed process-accelerating tools. The TTC has identified 2 major areas of emphasis: new biomarkers or endpoints for determining the efficacy of new therapies and new tools to assess the safety or tolerability of new therapies. This article presents the rationale and planned approach to develop new tools to assess safety and tolerability of therapies for transplant patients. We also discuss how similar efforts might support the continued development of patient-reported outcome measures in the future.
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- 2018
33. The Houston Methodist Lung Transplant Risk Model: A Validated Tool for Pretransplant Risk Assessment
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Edward A. Graviss, Duc T. Nguyen, T. Kaleekal, Edward Y. Chan, Brian A. Bruckner, A. Osama Gaber, Thomas E. MacGillivray, Neeraj Sinha, Simon W. Yau, Erik E. Suarez, Ahmad Goodarzi, and Howard J. Huang
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Pulmonary and Respiratory Medicine ,Lung Diseases ,Male ,medicine.medical_specialty ,Databases, Factual ,medicine.medical_treatment ,MEDLINE ,030204 cardiovascular system & hematology ,Risk Assessment ,03 medical and health sciences ,Risk model ,0302 clinical medicine ,Postoperative Complications ,Risk Factors ,Internal medicine ,medicine ,Lung transplantation ,Humans ,Aged ,Retrospective Studies ,Lung ,business.industry ,Gold standard ,Retrospective cohort study ,Middle Aged ,Texas ,Transplant Recipients ,Transplantation ,Survival Rate ,medicine.anatomical_structure ,030228 respiratory system ,Preoperative Period ,Surgery ,Female ,Cardiology and Cardiovascular Medicine ,Risk assessment ,business ,Lung Transplantation - Abstract
Lung transplantation is the gold standard for a carefully selected patient population with end-stage lung disease. This study sought to create a risk stratification model using only preoperative recipient data to predict 1-year postoperative mortality during the pretransplant assessment.Data of lung transplant recipients at Houston Methodist Hospital in Houston, Texas from January 2009 to December 2014 were extracted from the United Network for Organ Sharing (UNOS) database. Patients were randomly divided into development and validation cohorts. Cox proportional-hazards models were conducted. Variables associated with 1-year mortality after transplantation were assigned weights on the basis of the beta coefficients, and risk scores were derived. Patients were stratified into low-, medium- and high-risk categories. The model was validated using the validation data set and data from other US transplant centers in the UNOS database.The study randomized 633 lung recipients from Houston Methodist Hospital into development (n = 317 patients) and validation cohorts (n = 316). The 1-year survival after transplantation was significantly different among risk groups: 95% (low risk), 84% (medium risk), and 72% (high risk) (P.001), with a C-statistic of 0.74. Patient survival in the validation cohort was also significantly different among risk groups (85%, 77%, and 65%, respectively; P.001). Validation of the model with the UNOS data set included 9920 patients and found 1-year survival to be 91%, 86%, and 82%, respectively (P.001).Using only recipient data collected at the time of the prelisting evaluation, this simple scoring system was found to have good discrimination power and could be a practical tool in the assessment and selection of potential lung transplant recipients.
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- 2018
34. Disparate outcomes observed within Kidney Disease: Improving Global Outcomes (KDIGO) acute kidney injury stage 1
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A. Osama Gaber, Joshua T. Swan, Harlan G. Sparrow, Wadi N. Suki, and Linda W. Moore
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0301 basic medicine ,Adult ,Male ,medicine.medical_specialty ,Adolescent ,030232 urology & nephrology ,urologic and male genital diseases ,Severity of Illness Index ,03 medical and health sciences ,chemistry.chemical_compound ,Young Adult ,0302 clinical medicine ,Risk Factors ,Internal medicine ,medicine ,Humans ,Hospital Mortality ,Stage (cooking) ,Aged ,Retrospective Studies ,Aged, 80 and over ,Creatinine ,business.industry ,Incidence (epidemiology) ,Incidence ,Acute kidney injury ,Retrospective cohort study ,Odds ratio ,Acute Kidney Injury ,Length of Stay ,Middle Aged ,medicine.disease ,Prognosis ,Survival Analysis ,female genital diseases and pregnancy complications ,030104 developmental biology ,chemistry ,Nephrology ,Inclusion and exclusion criteria ,Disease Progression ,Female ,business ,Kidney disease ,Glomerular Filtration Rate - Abstract
The 2012 Kidney Disease: Improving Global Outcomes (KDIGO) clinical practice guideline classifies acute kidney injury (AKI) into 3 stages defined by serum creatinine elevation or urine output decline. We evaluated the potential impact of further categorizing AKI stage 1 into two stages based on serum creatinine criteria, with a focus on how the resulting 4-stage classification would affect the association of AKI stages with clinical outcomes. We defined AKI stage 1a as an absolute increase in serum creatinine of 0.3 mg/dl within 48 hours and stage 1b as a 50% relative increase in serum creatinine within 7 days. We screened all admissions to 5 hospitals from 2012 to 2014 using standardized inclusion and exclusion criteria and included 81,651 admissions in this retrospective cohort study. The incidence of in-hospital AKI was 7.5% for stage 1a, 4.9% for stage 1b, 1.5% for stage 2, and 0.9% for stage 3. Length of stay following the first incidence of AKI was 3.9 days for stage 1a, 6.2 days for stage 1b, 8.8 days for stage 2, and 12.0 days for stage 3. Compared to patients with no AKI, the odds of in-hospital mortality were progressively higher for patients with higher AKI stages (odds ratio 4.3 for patients with stage 1a, 10.9 for stage 1b, 40.6 for stage 2, and 60.0 for stage 3 AKI). Patients with AKI stages 1a and 1b experienced clinically meaningful and statistically significant differences in length of stay and mortality. This study suggests that a modified 4-stage version of the KDIGO AKI classification may provide additional prognostic information.
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- 2018
35. Transplantation in value-based care for patients with renal failure
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Osama Gaber, Timothy L. Pruett, Alan I. Reed, and Jean C. Emond
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Transplantation ,medicine.medical_specialty ,Tissue and Organ Procurement ,business.industry ,medicine.medical_treatment ,Value based care ,030230 surgery ,medicine.disease ,Kidney Transplantation ,Law legislation ,03 medical and health sciences ,Patient referral ,0302 clinical medicine ,medicine ,Living Donors ,Immunology and Allergy ,Humans ,Pharmacology (medical) ,030212 general & internal medicine ,Renal Insufficiency ,Intensive care medicine ,business ,Dialysis ,Kidney disease - Published
- 2018
36. Conversion from tacrolimus-mycophenolate mofetil to tacrolimus-mTOR immunosuppression after kidney-pancreas transplantation reduces the incidence of both BK and CMV viremia
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Samantha A. Kuten, Duc T. Nguyen, Lillian W. Gaber, Samir J. Patel, A. Osama Gaber, Richard J. Knight, and Edward A. Graviss
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Adult ,Graft Rejection ,Male ,medicine.medical_specialty ,medicine.medical_treatment ,Renal function ,Cytomegalovirus ,Viremia ,030230 surgery ,Pancreas transplantation ,Gastroenterology ,Mycophenolic acid ,Tacrolimus ,03 medical and health sciences ,Young Adult ,0302 clinical medicine ,Postoperative Complications ,Risk Factors ,Internal medicine ,medicine ,Humans ,Retrospective Studies ,Transplantation ,Polyomavirus Infections ,business.industry ,TOR Serine-Threonine Kinases ,Hazard ratio ,Graft Survival ,Immunosuppression ,Middle Aged ,Mycophenolic Acid ,medicine.disease ,Prognosis ,Kidney Transplantation ,Tumor Virus Infections ,BK Virus ,Cytomegalovirus Infections ,030211 gastroenterology & hepatology ,Female ,Pancreas Transplantation ,business ,Immunosuppressive Agents ,medicine.drug ,Follow-Up Studies - Abstract
Background We sought to determine whether conversion from tacrolimus/mycophenolate mofetil (TAC-MMF) into tacrolimus/mTOR inhibitor (TAC-mTOR) immunosuppression would reduce the incidences of BK and CMV viremia after kidney/pancreas (KP) transplantation. Methods In this single-center review, the TAC-mTOR cohort (n = 39) was converted at 1 month post-transplant to an mTOR inhibitor and reduced-dose tacrolimus. Outcomes were compared to a cohort of KP recipients (n = 40) maintained on TAC-MMF. Results At 3 years post-transplant, KP survivals and incidences of kidney/pancreas rejection were equivalent between mTOR and MMF-treated cohorts. (P = ns). BK viremia-free survival was better for the mTOR vs MMF-treated group (P = .004). In multivariate analysis, MMF vs mTOR immunosuppression was an independent risk factor for BK viremia (hazard ratio 12.27, P = .02). Similarly, mTOR-treated recipients displayed better CMV infection-free survival compared to the MMF-treated cohort (P = .01). MMF vs mTOR immunosuppression (hazard ratio 18.77, P = .001) and older recipient age (hazard ratio 1.13 per year, P = .006) were independent risk factors for CMV viremia. Mean estimated GFR and HgbA1c levels were equivalent between groups at 1, 2, and 3 years post-transplantation. Conclusion Conversion from TAC/MMF into TAC/mTOR immunosuppression after KP transplantation reduced the incidences of BK and CMV viremia with an equivalent risk of acute rejection and similar renal/pancreas function.
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- 2018
37. Transcutaneously refillable, 3D-printed biopolymeric encapsulation system for the transplantation of endocrine cells
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Danilo Demarchi, Ravi Ramesh Pathak, A. Osama Gaber, Alessandro Grattoni, Gianluca Torchio, Andrew G. Sikora, Joan E. Nichols, Ghanashyam Acharya, Raffaella Sesana, Jessica Rhudy, Daniel W. Fraga, Usha Thekkedath, Corrine Ying Xuan Chua, Marco Farina, Jenolyn F. Alexander, Jean A. Niles, Mariana Villanueva, Andrea Ballerini, and Crystal S. Shin
- Subjects
0301 basic medicine ,Male ,Cell Survival ,Polyesters ,Cell ,Pancreatic islets ,Biophysics ,3D printing ,Cell transplantation ,Leydig cells ,Subcutaneous implant ,Neovascularization, Physiologic ,Bioengineering ,Biocompatible Materials ,02 engineering and technology ,Hydrogel, Polyethylene Glycol Dimethacrylate ,Biomaterials ,03 medical and health sciences ,Islets of Langerhans ,Mice ,Human Umbilical Vein Endothelial Cells ,Medicine ,Autologous transplantation ,Animals ,Humans ,Cell encapsulation ,Cells, Cultured ,Leydig cell ,Tissue Engineering ,Tissue Scaffolds ,business.industry ,Leydig Cells ,Cells, Immobilized ,021001 nanoscience & nanotechnology ,Cell biology ,Transplantation ,Chorioallantoic membrane ,030104 developmental biology ,medicine.anatomical_structure ,Mechanics of Materials ,Printing, Three-Dimensional ,Ceramics and Composites ,0210 nano-technology ,business ,Homing (hematopoietic) - Abstract
Autologous cell transplantation holds enormous promise to restore organ and tissue functions in the treatment of various pathologies including endocrine, cardiovascular, and neurological diseases among others. Even though immune rejection is circumvented with autologous transplantation, clinical adoption remains limited due to poor cell retention and survival. Cell transplant success requires homing to vascularized environment, cell engraftment and importantly, maintenance of inherent cell function. To address this need, we developed a three dimensional (3D) printed cell encapsulation device created with polylactic acid (PLA), termed neovascularized implantable cell homing and encapsulation (NICHE). In this paper, we present the development and systematic evaluation of the NICHE in vitro, and the in vivo validation with encapsulated testosterone-secreting Leydig cells in Rag1-/- castrated mice. Enhanced subcutaneous vascularization of NICHE via platelet-rich plasma (PRP) hydrogel coating and filling was demonstrated in vivo via a chorioallantoic membrane (CAM) assay as well as in mice. After establishment of a pre-vascularized bed within the NICHE, transcutaneously transplanted Leydig cells, maintained viability and robust testosterone secretion for the duration of the study. Immunohistochemical analysis revealed extensive Leydig cell colonization in the NICHE. Furthermore, transplanted cells achieved physiologic testosterone levels in castrated mice. The promising results provide a proof of concept for the NICHE as a viable platform technology for autologous cell transplantation for the treatment of a variety of diseases.
- Published
- 2018
38. Efficacy and safety of eculizumab in atypical hemolytic uremic syndrome from 2-year extensions of phase 2 studies
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Petra Muus, David J. Cohen, Antonella Trivelli, Osama Gaber, Christoph Licht, Giuseppe Remuzzi, Sunil Babu, Camille L. Bedrosian, Maria Herthelius, Kenneth W. Douglas, Yahsou Delmas, Neil S. Sheerin, Chantal Loirat, Maryvonne Hourmant, Larry A. Greenbaum, Christophe Legendre, Timothy H.J. Goodship, and Richard R. Furman
- Subjects
Adult ,Male ,medicine.medical_specialty ,Pediatrics ,Thrombotic microangiopathy ,Adolescent ,Vascular damage Radboud Institute for Health Sciences [Radboudumc 16] ,030232 urology & nephrology ,Renal function ,030204 cardiovascular system & hematology ,Antibodies, Monoclonal, Humanized ,03 medical and health sciences ,Complement inhibitor ,aHUS ,Young Adult ,0302 clinical medicine ,Internal medicine ,Atypical hemolytic uremic syndrome ,medicine ,Humans ,complement ,Platelet activation ,Aged ,Atypical Hemolytic Uremic Syndrome ,business.industry ,Eculizumab ,Middle Aged ,medicine.disease ,3. Good health ,Clinical trial ,Treatment Outcome ,Nephrology ,Quality of Life ,eculizumab ,Female ,business ,chronic kidney disease ,medicine.drug ,Kidney disease ,Glomerular Filtration Rate - Abstract
Contains fulltext : 155154.pdf (Publisher’s version ) (Open Access) Atypical hemolytic uremic syndrome (aHUS) is a rare, possibly life-threatening disease characterized by platelet activation, hemolysis and thrombotic microangiopathy (TMA) leading to renal and other end-organ damage. We originally conducted two phase 2 studies (26 weeks and 1 year) evaluating eculizumab, a terminal complement inhibitor, in patients with progressing TMA (trial 1) and those with long duration of aHUS and chronic kidney disease (trial 2). The current analysis assessed outcomes after 2 years (median eculizumab exposure 100 and 114 weeks, respectively). At all scheduled time points, eculizumab inhibited terminal complement activity. In trial 1 with 17 patients, the platelet count was significantly improved from baseline, and hematologic normalization was achieved in 13 patients at week 26, and in 15 patients at both 1 and 2 years. The estimated glomerular filtration rate (eGFR) was significantly improved compared with baseline and year 1. In trial 2 with 20 patients, TMA event-free status was achieved by 16 patients at week 26, 17 patients at year 1, and 19 patients at year 2. Criteria for hematologic normalization were met by 18 patients at each time point. Improvement of 15 ml/min per 1.73 m(2) or more in eGFR was achieved by 1 patient at week 26, 3 patients at 1 year, and 8 patients at 2 years. The mean change in eGFR was not significant compared with baseline, week 26, or year 1. Eculizumab was well tolerated, with no new safety concerns or meningococcal infections. Thus, a 2-year analysis found that the earlier clinical benefits achieved by eculizumab treatment of aHUS were maintained at 2 years of follow-up.
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- 2015
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39. Risk Stratification of Patients With Current Generation Continuous-Flow Left Ventricular Assist Devices Being Bridged to Heart Transplantation
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Osama Gaber, Javier Amione-Guerra, Barry H. Trachtenberg, Arvind Bhimaraj, Guillermo Torre-Amione, Ashrith Guha, Myung H. Park, Robert C. Schutt, Eva Montané, Jerry D. Estep, Ana S. Cruz-Solbes, Erik E. Suarez, Edward A. Graviss, and Duc T.M. Nguyen
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Adult ,Male ,medicine.medical_specialty ,medicine.medical_treatment ,Biomedical Engineering ,Biophysics ,heart failure ,Bioengineering ,030204 cardiovascular system & hematology ,030230 surgery ,risk score ,heart transplantation ,Biomaterials ,03 medical and health sciences ,0302 clinical medicine ,Internal medicine ,medicine ,left ventricular assist device ,Humans ,Proportional Hazards Models ,Retrospective Studies ,Heart transplantation ,Heart Failure ,Framingham Risk Score ,business.industry ,Proportional hazards model ,General Medicine ,Middle Aged ,medicine.disease ,Decision Support Systems, Clinical ,Prognosis ,Transplantation ,Treatment Outcome ,Ventricular assist device ,Heart failure ,Cohort ,Cardiology ,Heart Transplantation ,Female ,Heart-Assist Devices ,business ,Body mass index - Abstract
Patients bridged to transplant (BTT) with continuous-flow left ventricular assist devices (CF-LVADs) have increased in the past decade. Decision support tools for these patients are limited. We developed a risk score to estimate prognosis and guide decision-making. We included heart transplant recipients bridged with CF-LVADs from the United Network for Organ Sharing (UNOS) database and divided them into development (2,522 patients) and validation cohorts (1,681 patients). Univariate and multivariate Cox proportional hazards models were performed. Variables that independently predicted outcomes (age, African American race, recipient body mass index [BMI], intravenous [IV] antibiotic use, pretransplant dialysis, and total bilirubin) were assigned weight using linear transformation, and risk scores were derived. Patients were grouped by predicted posttransplant mortality: low risk (≤ 38 points), medium risk (38-41 points), and high risk (≥ 42 points). We performed Cox proportional hazards analysis on wait-listed CF-LVAD patients who were not transplanted. Score significantly discriminated survival among the groups in the development cohort (6.7, 12.9, 20.7; p = 0.001), validation cohort (6.4, 10.1, 13.6; p < 0.001), and ambulatory cohort (6.4, 11.5, 17.2; p < 0.001). We derived a left ventricular assist device (LVAD) BTT risk score that effectively identifies CF-LVAD patients who are at higher risk for worse outcomes after heart transplant. This score may help physicians weigh the risks of transplantation in patients with CF-LVAD.
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- 2017
40. Optimal cut points of plasma and urine neutrophil gelatinase-associated lipocalin for the prediction of acute kidney injury among critically ill adults: retrospective determination and clinical validation of a prospective multicentre study
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Peter A. McCullough, Michael J. Germain, Linda W. Moore, Ladan Golestaneh, Maria de los Angeles Lavoria, Peter M Eriksen, Kristen M. Tecson, Elisabeth Erhardtsen, and A. Osama Gaber
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Male ,medicine.medical_specialty ,Critical Illness ,030232 urology & nephrology ,Urology ,specificity ,Urine ,030204 cardiovascular system & hematology ,Lipocalin ,Kidney ,Sensitivity and Specificity ,law.invention ,03 medical and health sciences ,risk prediction ,0302 clinical medicine ,Lipocalin-2 ,law ,medicine ,Humans ,Prospective Studies ,Stage (cooking) ,Aged ,Renal Medicine ,business.industry ,Critically ill ,Research ,Acute kidney injury ,General Medicine ,Acute Kidney Injury ,Middle Aged ,medicine.disease ,sensitivity ,Intensive care unit ,United States ,Surgery ,Neutrophil gelatinase-associated lipocalin ,Intensive Care Units ,Logistic Models ,ROC Curve ,Creatinine ,Female ,business ,Biomarkers ,Kidney disease ,neutrophil gelatinase associated lipocalin - Abstract
Objectives To determine the optimal threshold of blood and urine neutrophil gelatinase-associated lipocalin (NGAL) to predict moderate to severe acute kidney injury (AKI) and persistent moderate to severe AKI lasting at least 48 consecutive hours, as defined by an adjudication panel. Methods A multicentre prospective observational study enrolled intensive care unit (ICU) patients and recorded daily ethylenediaminetetraacetic acid (EDTA) plasma, heparin plasma and urine NGAL. We used natural log-transformed NGAL in a logistic regression model to predict stage 2/3 AKI (defined by Kidney Disease International Global Organization). We performed the same analysis using the NGAL value at the start of persistent stage 2/3 AKI. Results Of 245 subjects, 33 (13.5%) developed stage 2/3 AKI and 25 (10.2%) developed persistent stage 2/3 AKI. Predicting stage 2/3 AKI revealed the optimal NGAL cutoffs in EDTA plasma (142.0 ng/mL), heparin plasma (148.3 ng/mL) and urine (78.0 ng/mL) and yielded the following decision statistics: sensitivity (SN)=78.8%, specificity (SP)=73.0%, positive predictive value (PPV)=31.3%, negative predictive value (NPV)=95.7%, diagnostic accuracy (DA)=73.8% (EDTA plasma); SN=72.7%, SP=73.8%, PPV=30.4%, NPV=94.5%, DA=73.7% (heparin plasma); SN=69.7%, SP=76.8%, PPV=32.9%, NPV=94%, DA=75.8% (urine). The optimal NGAL cutoffs to predict persistent stage 2/3 AKI were similar: 148.3 ng/mL (EDTA plasma), 169.6 ng/mL (heparin plasma) and 79.0 ng/mL (urine) yielding: SN=84.0%, SP=73.5%, PPV=26.6%, NPV=97.6, DA=74.6% (EDTA plasma), SN=84%, SP=76.1%, PPV=26.8%, NPV=96.5%, DA=76.1% (heparin plasma) and SN=75%, SP=75.8%, PPV=26.1, NPV=96.4%, DA=75.7% (urine). Conclusion Blood and urine NGAL predicted stage 2/3 AKI, as well as persistent 2/3 AKI in the ICU with acceptable decision statistics using a single cut point in each type of specimen.
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- 2017
41. The detrimental impact of persistent vs an isolated occurrence of de novo donor-specific antibodies on intermediate-term renal transplant outcomes
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A. Osama Gaber, Larry D. Teeter, Richard J. Knight, Samir J. Patel, Edward A. Graviss, Todd N. Eagar, and Jennifer M. Loucks‐DeVos
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Adult ,Graft Rejection ,Male ,medicine.medical_specialty ,Urology ,Kaplan-Meier Estimate ,030230 surgery ,Persistence (computer science) ,Isoantibodies ,03 medical and health sciences ,0302 clinical medicine ,Risk Factors ,medicine ,Humans ,Prospective Studies ,Prospective cohort study ,Kidney transplantation ,Aged ,Proportional Hazards Models ,Intermediate term ,Aged, 80 and over ,Transplantation ,business.industry ,Proportional hazards model ,Graft Survival ,Case-control study ,Middle Aged ,medicine.disease ,Kidney Transplantation ,Surgery ,Logistic Models ,Renal transplant ,Case-Control Studies ,Female ,business ,030215 immunology ,Follow-Up Studies - Abstract
Background De novo donor-specific antibodies (dnDSA) after renal transplant are associated with acute rejection (AR) and graft loss, yet most recipients with dnDSA have stable function and no AR. We assessed whether the persistence of dnDSA increased the risk of a detrimental outcome. Methods A single-center review of renal transplant recipients monitored for dnDSA at multiple time points post-transplant. An Isolated dnDSA was defined as one positive dnDSA and no additional positive tests, whereas ≥2 positive dnDSA was defined as persistent dnDSA. Results Of 708 recipients, 22% developed dnDSA, of whom 64% had persistent dnDSA. At median follow-up of 35 (range 12-74) months, there were fewer episodes of AR in the isolated dnDSA vs the persistent dnDSA group (2% vs 22%; P
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- 2017
42. Incidence and Factors Associated with De Novo DSA After BK Viremia in Renal Transplant Recipients
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Samir J, Patel, Samantha A, Kuten, Richard J, Knight, Edward A, Graviss, Duc, Nguyen, and A Osama, Gaber
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Polyomavirus Infections ,Tumor Virus Infections ,BK Virus ,Incidence ,Humans ,Viremia ,Kidney Transplantation ,Retrospective Studies - Abstract
BK polyomavirus infection and de novo donor-human leukocyte antigen (HLA) specific antibodies (dnDSA) are two well-known and distinct complications occurring after kidney transplantation. Recent literature suggests an association between the two events. This study aims to examine the relationship between BK viremia (BKV) and dnDSA and to identify potential risk factors for dnDSA following BKV in kidney transplant recipients. A retrospective review of 1019 recipients from Houston Methodist Hospital was conducted. All patients underwent routine screening for BKV and dnDSA. Median follow-up was 44 months. BKV was detected in 186 (18%) patients at a median of 107 (82-205) days post-transplant. dnDSA occurred in 283 (28%) patients at a median of 272 (62-575) days post-transplant. Of the 69 dnDSA-positive/BKV-positive patients, dnDSA detection occurred after BKV onset in 46 patients. Thus, 46 (28%) previously DSA-negative patients later became dnDSA-positive following BKV, not significantly different from the rate seen in BKV-negative patients (26%; p=0.5). Median time to DSA detection following BKV onset was 232 days (interquartile range, 119-460) post-BKV detection. Multivariate analysis revealed a greater number of HLA mismatches and viral clearance as risk factors for development of dnDSA following BKV, whereas delayed graft function was associated with a lower risk of dnDSA. In conclusion, despite being considered a result of over-immunosuppression, BKV can still be followed by dnDSA in a substantial proportion of patients. Monitoring for dnDSA in patients being managed for BKV may be warranted.
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- 2017
43. Hospital readmissions following HLA-incompatible live donor kidney transplantation: A multi-center study
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Sandip Kapur, Dorry L. Segev, Paul W. Nelson, Jacqueline Garonzik-Wang, Ty B. Dunn, Xun Luo, A. Osama Gaber, Sunjae Bae, Bashir R. Sankari, Debra L. Sudan, Lloyd E. Ratner, Elizabeth A. King, John P. Roberts, Michael A. Rees, Adel Bozorgzadeh, Pooja Singh, David A. Gerber, Stanley C. Jordan, Matthew Cooper, Mark D. Stegall, Jason R. Wellen, Babak J. Orandi, Ronald P. Pelletier, Robert A. Montgomery, Ron Shapiro, Jose Oberholzer, George S. Lipkowitz, Marc P. Posner, Christopher L. Marsh, Marc L. Melcher, and Jose M. El-Amm
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Male ,Pediatrics ,Kidney Disease ,Live donor ,030232 urology & nephrology ,kidney transplantation/nephrology ,030230 surgery ,Kidney Function Tests ,Medical and Health Sciences ,Kidney Failure ,0302 clinical medicine ,Postoperative Complications ,hospital readmission ,quality of care ,HLA Antigens ,Isoantibodies ,Risk Factors ,care delivery ,Living Donors ,Immunology and Allergy ,living donor [kidney transplantation] ,organ transplantation in general ,Pharmacology (medical) ,Chronic ,Kidney transplantation ,Graft Survival ,Panel reactive antibody ,Middle Aged ,Prognosis ,practice ,Hospitalization ,Blood Group Incompatibility ,Cohort ,symbols ,Female ,Glomerular Filtration Rate ,Adult ,medicine.medical_specialty ,desensitization ,Renal and urogenital ,nephrology ,kidney transplantation ,Human leukocyte antigen ,clinical research/practice ,Lower risk ,Patient Readmission ,Article ,03 medical and health sciences ,symbols.namesake ,Clinical Research ,Diabetes mellitus ,quality of care/care delivery ,medicine ,Humans ,Poisson regression ,Transplantation ,business.industry ,economics ,Organ Transplantation ,health services and outcomes research ,medicine.disease ,Kidney Transplantation ,Case-Control Studies ,Kidney Failure, Chronic ,Surgery ,business ,Follow-Up Studies - Abstract
Thirty percent of kidney transplant recipients are readmitted in the first month posttransplantation. Those with donor-specific antibody requiring desensitization and incompatible live donor kidney transplantation (ILDKT) constitute a unique subpopulation that might be at higher readmission risk. Drawing on a 22-center cohort, 379 ILDKTs with Medicare primary insurance were matched to compatible transplant-matched controls and to waitlist-only matched controls on panel reactive antibody, age, blood group, renal replacement time, prior kidney transplantation, race, gender, diabetes, and transplant date/waitlisting date. Readmission risk was determined using multilevel, mixed-effects Poisson regression. In the first month, ILDKTs had a 1.28-fold higher readmission risk than compatible controls (95% confidence interval [CI] 1.13-1.46; P 
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- 2017
44. Corrections to: Checkpoint inhibitor therapy for cancer in solid organ transplantation recipients: an institutional experience and a systematic review of the literature
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Ala Abudayyeh, Van Anh Trinh, Chrystia M. Zobniw, Heather Lin, Michael K. Wong, Noha Abdel-Wahab, Maen Abdelrahim, A. Osama Gaber, Adi Diab, Maria E. Suarez-Almazor, Houssein Safa, and Daniel H. Johnson
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Adult ,Graft Rejection ,Male ,Oncology ,Cancer Research ,medicine.medical_specialty ,Adolescent ,medicine.medical_treatment ,Immune checkpoint inhibitors ,Programmed Cell Death 1 Receptor ,Immunology ,Risk Assessment ,lcsh:RC254-282 ,Young Adult ,Antineoplastic Agents, Immunological ,Neoplasms ,Internal medicine ,medicine ,Humans ,Transplantation, Homologous ,Immunology and Allergy ,CTLA-4 Antigen ,Aged ,Retrospective Studies ,Pharmacology ,business.industry ,Correction ,Cancer ,Organ Transplantation ,Immunotherapy ,Middle Aged ,medicine.disease ,lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,Treatment Outcome ,Molecular Medicine ,Female ,Solid organ transplantation ,business ,Immunosuppressive Agents ,Follow-Up Studies - Abstract
Checkpoint inhibitors (CPIs) have revolutionized the treatment of cancer, but their use remains limited by off-target inflammatory and immune-related adverse events. Solid organ transplantation (SOT) recipients have been excluded from clinical trials owing to concerns about alloimmunity, organ rejection, and immunosuppressive therapy. Thus, we conducted a retrospective study and literature review to evaluate the safety of CPIs in patients with cancer and prior SOT.Data were collected from the medical records of patients with cancer and prior SOT who received CPIs at The University of Texas MD Anderson Cancer Center from January 1, 2004, through March 31, 2018. Additionally, we systematically reviewed five databases through April 2018 to identify studies reporting CPIs to treat cancer in SOT recipients. We evaluated the safety of CPIs in terms of alloimmunity, immune-related adverse events, and mortality. We also evaluated tumor response to CPIs.Thirty-nine patients with allograft transplantation were identified. The median age was 63 years (range 14-79 years), 74% were male, 62% had metastatic melanoma, 77% received anti-PD-1 agents, and 59% had prior renal transplantation, 28% hepatic transplantation, and 13% cardiac transplantation. Median time to CPI initiation after SOT was 9 years (range 0.92-32 years). Allograft rejection occurred in 41% of patients (11/23 renal, 4/11 hepatic, and 1/5 cardiac transplantations), at similar rates for anti-CTLA-4 and anti-PD-1 therapy. The median time to rejection was 21 days (95% confidence interval 19.3-22.8 days). There were no associations between time since SOT and frequency, timing, or type of rejection. Overall, 31% of patients permanently discontinued CPIs because of allograft rejection. Graft loss occurred in 81%, and death was reported in 46%. Of the 12 patients with transplantation biopsies, nine (75%) had acute rejection, and five of these rejections were T cell-mediated. In melanoma patients, 36% responded to CPIs.SOT recipients had a high allograft rejection rate that was observed shortly after CPI initiation, with high mortality rates. Further studies are needed to optimize the anticancer treatment approach in these patients.
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- 2019
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45. The Transplant Center and Business Unit as a Model for Specialized Care Delivery
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Roberta L. Schwartz, David P. Bernard, Susan Zylicz, and A. Osama Gaber
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Transplantation ,Parent organization ,business.industry ,Hospital Departments ,Guidelines as Topic ,Medicare ,United States ,Patient care ,surgical procedures, operative ,Nursing ,Strategic business unit ,Models, Organizational ,Outcome Assessment, Health Care ,Health care ,Costs and Cost Analysis ,Humans ,Medicine ,Surgery ,Center (algebra and category theory) ,business ,Delivery of Health Care ,Diagnosis-Related Groups - Abstract
Transplant centers are valuable assets to a transplantation hospital and essential to organize the delivery of patient care. A transplant center defined around physicians and activities of caring for patients with organ failure creates a team better equipped to manage care across the continuum of the diseases treated by transplantation. Through monitoring of clinical and financial outcomes, the transplant center can better respond to the changing regulatory and financial landscape of health care. This article seeks to explain the major organizational challenges facing the transplant center and how a transplant center can best serve its patients and parent organization.
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- 2013
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46. Acute Rejection Characteristics From a Prospective, Randomized, Double-Blind, Placebo-Controlled Multicenter Trial of Early Corticosteroid Withdrawal
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A Osama, Gaber, Linda W, Moore, Rita R, Alloway, E Steve, Woodle, John, Pirsch, Fuad, Shihab, Alice, Henning, William, Fitzsimmons, John, Holman, Robin, Reisfield, and M Roy, First
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Graft Rejection ,medicine.medical_specialty ,Time Factors ,medicine.drug_class ,Biopsy ,Placebo ,Gastroenterology ,Drug Administration Schedule ,Tacrolimus ,law.invention ,Double-Blind Method ,Randomized controlled trial ,Adrenal Cortex Hormones ,HLA Antigens ,Risk Factors ,Prednisone ,law ,Internal medicine ,Multicenter trial ,Odds Ratio ,medicine ,Humans ,Prospective Studies ,Prospective cohort study ,Kidney transplantation ,Antilymphocyte Serum ,Proportional Hazards Models ,Transplantation ,business.industry ,Graft Survival ,Age Factors ,Mycophenolic Acid ,medicine.disease ,Kidney Transplantation ,United States ,Black or African American ,Treatment Outcome ,Histocompatibility ,Acute Disease ,Multivariate Analysis ,Corticosteroid ,Drug Therapy, Combination ,business ,Immunosuppressive Agents ,medicine.drug - Abstract
This report characterizes acute rejection and rejection outcomes in subjects randomized to continuous corticosteroid therapy (CCS) or early corticosteroid withdrawal (CSWD; 7 days after transplantation) in the Astellas Blinded CSWD Trial.The Astellas Blinded CSWD Trial was a 5-year, prospective, multicenter, randomized, double-blind trial of early CCS withdrawal in 386 kidney transplant recipients (195 CCS and 191 CSWD). Tacrolimus and mycophenolate mofetil were required as well as either rabbit antithymocyte globulin or interleukin-2 receptor antibody induction. Biopsy-confirmed acute rejection (BCAR) was grade 1A or higher by Banff criteria. This report also provides borderline changes (BL) that did not meet Banff grade 1A included with BCAR (BCAR+BL).BCAR+BL was 25 (12.8%) in CCS group and 42 (22.0%) in CSWD group (P=0.022). Early BCAR+BL (first 90 days after transplantation) was less frequent in CCS (n=5 [2.6%]) than in CSWD (n=22 [11.5%]; P0.001). Among non-African-American subjects, early BCAR+BL occurred more often in CSWD (n=20 [12.7%]) versus CCS (n=2 [1.3%]; P0.001). Late acute rejection (2 years) occurred more often in African-American subjects in CCS (n=5 [13.9%]) than in CSWD (n=0; P=0.056). Risk factors were CSWD (hazard ratio [HR], 4.72; P0.002) and human leukocyte antigen mismatch (HR, 1.48; P0.005) for early BCAR+BL and CSWD (HR, 1.9; P0.02), human leukocyte antigen mismatch (HR, 1.2; P0.01), and age (HR, 0.97; P0.002) for 5-year rejection. The HR for graft loss associated with BCAR+BL was 8.8.BCAR+BL may occur more frequently during the early period after transplantation under an early CSWD regimen with tacrolimus plus induction compared with CCS, particularly among non-African-Americans.
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- 2013
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47. Serum undercarboxylated osteocalcin correlates with hemoglobin A1c in children with recently diagnosed pediatric diabetes
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Maria J, Redondo, Beverly A, Shirkey, Daniel W, Fraga, A Osama, Gaber, and Omaima M, Sabek
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Glycated Hemoglobin ,Male ,Diabetes Mellitus, Type 1 ,C-Peptide ,Osteocalcin ,Humans ,Female ,Prospective Studies ,Child - Abstract
Osteocalcin (OC), a hormone secreted by osteoblasts, improves beta-cell function in vitro and in vivo. We aimed to understand the relationship between OC and hemoglobin A1c (HbA1c) in pediatric diabetes.Children (n = 70; mean [SD] age = 11.8 years [3.1]; 34.3% non-Hispanic white, 46.3% Hispanic, 14.9% African-American, 4.5% other) newly diagnosed with diabetes (69.1% type 1 diabetes [T1D], 30.9% type 2 diabetes [T2D]) were studied. We collected clinical data at diagnosis and first clinical visit (V1) 9 weeks later (interquartile range [IQR] = 7.9-12.0). Serum undercarboxylated OC (uOC) and carboxylated OC (cOC) were measured 7.0 weeks (IQR 4.3-8.9) after diagnosis.Mean [SD] uOC was 20.3 (19.6) ng/mL, cOC 29.7 [13.7] ng/mL and u/cOC 0.68 [0.81]. uOC, cOC, or u/cOC were not different by gender, race/ethnicity, age, diabetes type, BMI percentile, or random C-peptide, glucose or HbA1c at diagnosis. However, among 61 children with V1 within 4 months of diagnosis, uOC was higher in those with V1 HbA1c 7.5% (HbA1c 58 mmol/mol) (uOC=33.1 [22.0]) compared with children with HbA1c ≥ 7.5% (uOC=17.4 [2.3], P = .0004). The difference was larger among patients with T2D (34.6 and 4.7 ng/mL, respectively, P = .0001) than T1D (32.2 and 19.3, P = .0169), and in males (36.1 and 17.4, P = .018) than females (27.6 and 17.3, P = .072). Analysis for u/cOC were similar while there were no differences in cOC. uOC was inversely correlated with HbA1c at V1 (Spearman's rho = -0.29, P = .02).Our findings suggest that serum uOC is inversely related to HbA1c shortly after diagnosis of pediatric diabetes. This potentially modifiable factor of glucose metabolism warrants further studies.
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- 2016
48. Disparate rates of acute rejection and donor-specific antibodies among high-immunologic risk renal transplant subgroups receiving antithymocyte globulin induction
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Samir J. Patel, Duc T. Nguyen, Lillian W. Gaber, Wadi N. Suki, Jennifer Loucks-Devos, Larry D. Teeter, A. Osama Gaber, Samantha A. Kuten, Linda W. Moore, Richard J. Knight, and Edward A. Graviss
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Adult ,Graft Rejection ,Male ,medicine.medical_specialty ,Globulin ,medicine.medical_treatment ,030230 surgery ,Gastroenterology ,Antibodies ,03 medical and health sciences ,Young Adult ,0302 clinical medicine ,Risk Factors ,Internal medicine ,Living Donors ,Medicine ,Humans ,Anti-lymphocyte globulin ,Risk factor ,Antilymphocyte Serum ,Proportional Hazards Models ,Retrospective Studies ,Immunosuppression Therapy ,Transplantation ,biology ,business.industry ,Donor specific antibodies ,Incidence (epidemiology) ,Graft Survival ,Immunosuppression ,Middle Aged ,Kidney Transplantation ,Black or African American ,Renal transplant ,Immunology ,biology.protein ,Kidney Failure, Chronic ,030211 gastroenterology & hepatology ,Female ,Antibody ,business ,Immunosuppressive Agents - Abstract
Lymphocyte-depleting induction lowers acute rejection (AR) rates among high-immunologic risk (HIR) renal transplant recipients, including African Americans (AAs), retransplants, and the sensitized. It is unclear whether different HIR subgroups experience similarly low rates of AR. We aimed to describe the incidence of AR and de novo donor-specific antibody (dnDSA) among HIR recipients categorized by age, race, or donor type. All received antithymocyte globulin (ATG) induction and triple maintenance immunosuppression. A total of 464 HIR recipients from 2007 to 2014 were reviewed. AR and dnDSA rates at 1 year for the entire population were 14% and 27%, respectively. AR ranged from 6.7% among living donor (LD) recipients to 30% in younger AA deceased donor (DD) recipients. De novo donor-specific antibody at 1 year ranged from 7% in older non-AA LD recipients to 32% in AAs. AA race remained as an independent risk factor for AR among DD recipients and for dnDSA among all HIR recipients. Development of both AR and dnDSA within the first year was associated with a 54% graft survival at 5 years and was an independent risk factor for graft loss. Despite utilization of recommended immunosuppression for HIR recipients, substantial disparities exist among subgroups, warranting further consideration of individualized immunosuppression in certain HIR subgroups.
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- 2016
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49. Simultaneous Scalp, Skull, Kidney, and Pancreas Transplant from a Single Donor
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Todd Trask, Peirong Yu, Jesse C. Selber, Mark W. Clemens, Roman J. Skoracki, Lillian W. Gaber, A. Osama Gaber, Edward I. Chang, Michael J Klebuc, and Matthew M. Hanasono
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Leiomyosarcoma ,Male ,Reoperation ,medicine.medical_specialty ,Skin Neoplasms ,Tissue and Organ Procurement ,Osteoradionecrosis ,medicine.medical_treatment ,030230 surgery ,Pancreas transplantation ,Vascularized Composite Allotransplantation ,Parietal Bone ,03 medical and health sciences ,0302 clinical medicine ,medicine ,Humans ,Diabetic Nephropathies ,Intersectoral Collaboration ,Kidney transplantation ,Scalp ,business.industry ,Skull ,Immunosuppression ,Middle Aged ,medicine.disease ,Combined Modality Therapy ,Kidney Transplantation ,Tissue Donors ,Surgery ,medicine.anatomical_structure ,Diabetes Mellitus, Type 1 ,030220 oncology & carcinogenesis ,Tissue and Organ Harvesting ,Interdisciplinary Communication ,Radiotherapy, Adjuvant ,Solid organ ,Pancreas Transplantation ,Composite Tissue Allografts ,Pancreas ,business ,Follow-Up Studies - Abstract
Vascularized composite allotransplantation is an emerging field, but the complications of lifelong immunosuppression limit indications. Vascularized composite allotransplantation in solid organ recipients represents a unique opportunity because immunosuppression has already been accepted. This report of a simultaneous scalp, skull, kidney, and pancreas transplant represents both the first skull-scalp transplant and combination of a vascularized composite allotransplantation with double organ transplantation.A previous recipient of a kidney-pancreas transplant presented with osteoradionecrosis of the calvaria and a large area of unstable scalp following successful, curative treatment of a scalp tumor. His kidney and pancreas functions were also critically poor. A multidisciplinary, multi-institutional plan was developed to perform a simultaneous scalp, skull, and repeated kidney and pancreas transplantation, all from a single donor.Eighteen months after the patient was listed with the United Network for Organ Sharing, a donor was identified and the multiorgan vascularized composite allotransplantation was performed. Twenty physicians and 15 hours were required to perform donor and recipient procedures. The patient recovered well and was discharged on postoperative day 15. He has had one episode of scalp rejection confirmed by biopsy and treated successfully. His creatinine value is currently 0.8 mg/dl, from 5.0 mg/dl, and his blood glucose levels are normal without supplemental insulin. Aesthetic outcome is very satisfactory. The patient is now 1 year post-transplantation and doing well.Vascularized composite allotransplantation in solid organ recipients is an expansion of current indications to already immunosuppressed patients. Rejection of the vascularized composite allotransplant without solid organ rejection can occur and is treatable. Methodical planning, an interdisciplinary approach, and careful management of all organs are critical to success.Therapeutic, V.
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- 2016
50. Poor immune reconstitution is associated with symptomatic BK polyomavirus viruria in allogeneic stem cell transplant recipients
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Jeffrey J. Tarrand, Amir Hamdi, Valda D. Page, Uday R. Popat, Katayoun Rezvani, Roy F. Chemaly, Gabriela Rondon, Borje S. Andersson, Heather Lin, David Marin, Sairah Ahmed, Roy B. Jones, Charles Martinez, Aimaz Afrough, Islam Abudayyeh, Betul Oran, Dimitrios P. Kontoyiannis, Richard E. Champlin, Ala Abudayyeh, A. Osama Gaber, Maen Abdelrahim, Amanda Olson, and Elizabeth J. Shpall
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Male ,Urologic Diseases ,Transplantation Conditioning ,Graft vs Host Disease ,030230 surgery ,medicine.disease_cause ,Risk Assessment ,03 medical and health sciences ,0302 clinical medicine ,Immune system ,medicine ,Humans ,Transplantation, Homologous ,Retrospective Studies ,Transplantation ,Polyomavirus Infections ,business.industry ,Proportional hazards model ,Hematopoietic Stem Cell Transplantation ,Cancer ,Middle Aged ,Myeloablative Agonists ,medicine.disease ,BK virus ,Tumor Virus Infections ,surgical procedures, operative ,Infectious Diseases ,Cord blood ,BK Virus ,Immunology ,Female ,Virus Activation ,business ,CD8 ,030215 immunology ,Hemorrhagic cystitis - Abstract
Background BK polyomavirus (BKPyV) infections are known indicators of immune suppression in hematopoietic stem cell transplant (HSCT) recipients; they can lead to hemorrhagic cystitis, ureteral stenosis, renal dysfunction, and prolonged hospital stays. In this study, we determined transplant-associated variables and immune parameters that can predict for the risk of BKPyV viruria. We hypothesized that BKPyV infection is a marker of poor immune recovery. Methods We analyzed all engrafted patients undergoing first allogeneic HSCT at MD Anderson Cancer Center in Houston between January 2004 and December 2012. We evaluated their immune parameters and their transplant-associated factors. BKPyV positivity was defined as BKPyV detection in urine by polymerase chain reaction testing. Cox proportional hazards model, as well as competing risk analysis method using subdistribution hazard models with death as competing risk, were applied to assess risk of BK viruria. Results We identified a total of 2477 patients with a median age of 52 years. BK viruria was manifest in 25% (n=629) of the patients. The median time from transplantation to BK viruria development was 42 days among the patients who had BK viruria. On multivariate analysis, tumor type, acute GVHD, chronic GVHD, myeloablative conditioning regimen, cord blood as the graft source, CD3+, CD4+, CD8+, CD56+, NK counts, and low platelet count were shown to be significantly associated with BKPyV infection. These finding were further confirmed when models incorporating the competing risk of death yielded similar findings. Conclusion In this study, we report significant associations between BKPyV reactivation following allogeneic HSCT and suppressed immune variables. In addition, this study provides valuable information on the immune status of HSCT recipients as a predictor of BKPyV infections that may in turn help us formulate plans for more effective prevention and treatment of this infection. This article is protected by copyright. All rights reserved.
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- 2016
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