143 results on '"Claus U. Niemann"'
Search Results
2. Machine Learning Prediction of Liver Allograft Utilization From Deceased Organ Donors Using the National Donor Management Goals Registry
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Andrew M. Bishara, MD, Dmytro S. Lituiev, PhD, Dieter Adelmann, MD, PhD, Rishi P. Kothari, MD, Darren J. Malinoski, MD, Jacob D. Nudel, MD, Mitchell B. Sally, MD, Ryutaro Hirose, MD,, Dexter D. Hadley, MD, PhD, and Claus U. Niemann, MD
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Surgery ,RD1-811 - Abstract
Background. Early prediction of whether a liver allograft will be utilized for transplantation may allow better resource deployment during donor management and improve organ allocation. The national donor management goals (DMG) registry contains critical care data collected during donor management. We developed a machine learning model to predict transplantation of a liver graft based on data from the DMG registry. Methods. Several machine learning classifiers were trained to predict transplantation of a liver graft. We utilized 127 variables available in the DMG dataset. We included data from potential deceased organ donors between April 2012 and January 2019. The outcome was defined as liver recovery for transplantation in the operating room. The prediction was made based on data available 12–18 h after the time of authorization for transplantation. The data were randomly separated into training (60%), validation (20%), and test sets (20%). We compared the performance of our models to the Liver Discard Risk Index. Results. Of 13 629 donors in the dataset, 9255 (68%) livers were recovered and transplanted, 1519 recovered but used for research or discarded, 2855 were not recovered. The optimized gradient boosting machine classifier achieved an area under the curve of the receiver operator characteristic of 0.84 on the test set, outperforming all other classifiers. Conclusions. This model predicts successful liver recovery for transplantation in the operating room, using data available early during donor management. It performs favorably when compared to existing models. It may provide real-time decision support during organ donor management and transplant logistics.
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- 2021
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3. Longer Distance From Dialysis Facility to Transplant Center Is Associated With Lower Access to Kidney Transplantation
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Adrian M. Whelan, MB BCh BAO, MAS, Kirsten L. Johansen, MD, Charles E. McCulloch, PhD, Dieter Adelmann, MD, PhD, Claus U. Niemann, MD, Garrett R. Roll, MD, Salpi Siyahian, BS, Barbara Grimes, PhD, and Elaine Ku, MD, MAS
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Surgery ,RD1-811 - Abstract
Background. Rates of kidney transplantation vary substantially across dialysis facilities in the United States. Whether distance between the dialysis facility and transplant center associates with variations in transplantation rates has not been examined. Methods. We performed a retrospective study of adults treated with dialysis between 2005 and 2015, according to the US Renal Data System. We examined the association between distance from dialysis facility to transplant center and time to kidney transplantation (primary outcome) and waitlist registration (secondary outcome) using Fine-Gray models. We also performed sensitivity analyses using the distance from each patient’s dialysis facility to the nearest transplant center as the predictor so that patients who were never registered on the waitlist (and therefore would not have a transplant center) could be included. Results. In total, 178 885 waitlisted patients were included for our primary analysis. As distance between dialysis facility and transplant center increased, lower hazard of transplantation (subhazard ratio [HR], 0.92; 95% confidence interval [CI], 0.91-0.94, if distance was 10 to
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- 2020
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4. Intraoperative Hyperglycemia Augments Ischemia Reperfusion Injury in Renal Transplantation: A Prospective Study
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Justin Parekh, Claus U. Niemann, Kim Dang, and Ryutaro Hirose
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Surgery ,RD1-811 - Abstract
Background. Diabetes is a risk factor for delayed graft function in kidney transplantation, and hyperglycemia increases ischemia reperfusion injury in animal models. Methods. To explore the role of perioperative hyperglycemia in ischemia reperfusion injury, we conducted a prospective study of 40 patients undergoing living donor renal transplantation. Blood glucose levels were monitored intraoperatively, and serum samples were obtained at the time anesthesia was induced and one hour after allograft reperfusion. The percentage change in neutrophil gelatinase-associated lipocalin (NGAL), a protein whose expression is increased with renal ischemia, was then used to determine the extent of injury. Results. In a multivariate model including recipient, donor, and transplant factors, recipient blood glucose >160 mg/dL at the time of allograft reperfusion (β 0.19, P-value < 0.01), warm ischemia time >30 minutes (β 0.11, P-value 0.13), and recipient age (β 0.05, P-value 0.05) were associated with percentage change in NGAL. These same predictors were associated with the percentage change in creatinine on postoperative day 2. Conclusions. Hyperglycemia is associated with increased ischemic injury in renal transplantation. Both creatinine and NGAL, a marker of ischemic injury and renal function, fall less rapidly in patients with elevated blood glucose.
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- 2011
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5. Hypothermia or Machine Perfusion in Kidney Donors
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Darren Malinoski, Christina Saunders, Sharon Swain, Tahnee Groat, Patrick R. Wood, Jeffrey Reese, Rachel Nelson, Jennifer Prinz, Kate Kishish, Craig Van De Walker, P.J. Geraghty, Kristine Broglio, and Claus U. Niemann
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General Medicine - Published
- 2023
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6. Critical care and ventilatory management of deceased organ donors impact lung use and recipient graft survival
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Michael P. Hutchens, Tahnee Groat, Elizabeth A. Swanson, Claus U. Niemann, Mitchell B. Sally, Darren Malinoski, and Madhukar S. Patel
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Brain Death ,Tissue and Organ Procurement ,Critical Care ,Demographics ,medicine.medical_treatment ,Body weight ,law.invention ,Randomized controlled trial ,law ,medicine ,Humans ,Immunology and Allergy ,Pharmacology (medical) ,Lung ,Donor management ,Mechanical ventilation ,Transplantation ,business.industry ,Graft Survival ,respiratory system ,Tissue Donors ,respiratory tract diseases ,medicine.anatomical_structure ,Anesthesia ,Graft survival ,business ,Blood ph - Abstract
Current risk-adjusted models for donor lung use and lung graft survival do not include donor critical care data. We sought to identify modifiable donor physiologic and mechanical ventilation parameters that predict donor lung use and lung graft survival. This is a prospective observational study of donors after brain death (DBDs) managed by 19 Organ Procurement Organizations from 2016 to 2019. Demographics, mechanical ventilation parameters, and critical care data were recorded at standardized time points during donor management. The lungs were transplanted from 1811 (30%) of 6052 DBDs. Achieving ≥7 critical care endpoints was a positive predictor of donor lung use. After controlling for recipient factors, donor blood pH positively predicted lung graft survival (OR 1.48 per 0.1 unit increase in pH) and the administration of dopamine during donor management negatively predicted lung graft survival (OR 0.19). Tidal volumes ≤8 ml/kg predicted body weight (OR 0.65), and higher positive end-expiratory pressures (OR 0.91 per cm H2 O) predicted decreased donor lung use without affecting lung graft survival. A randomized clinical trial is needed to inform optimal ventilator management strategies in DBDs.
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- 2021
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7. Assessment of the global practice of living donor liver transplantation
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Yuri Genyk, Claus U. Niemann, Yong Kwon, Linda Sher, Pranay Singh, Michelle H Kim, Cameron Goldbeck, Juliet Emamaullee, and Claire Conrad
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Adult ,Transplantation ,Adolescent ,Donor selection ,business.industry ,medicine.medical_treatment ,Arterial reconstruction ,Middle Aged ,Liver transplantation ,Living donor ,Body Mass Index ,Donor Selection ,Liver Transplantation ,Europe ,Limited access ,Young Adult ,Treatment Outcome ,Living Donors ,medicine ,Global health ,Humans ,business ,Living donor liver transplantation ,Body mass index ,Demography - Abstract
Criteria that drive the selection and utilization of living liver donors are limited. Herein, the global availability of living donor liver transplantation (LDLT) and components of donor selection and utilization were assessed via an international survey. There were 124 respondents representing 41 countries, including 47 from Asia/Middle East (A/ME), 20 from Europe, and 57 from the Americas. Responses were obtained from 94.9% of countries with ≥10 LDLT cases/year. Most centers (82.3%) have defined donor age criteria (median 18-60 years), while preset recipient MELD cutoffs (median 18-30) were only reported in 54.8% of programs. Overall, 67.5% of programs have preset donor BMI (body mass index) ranges (median 18-30), and the mean acceptable macrosteatosis was highest for A/ME (20.2 ± 9.2%) and lowest for Americas (16.5 ± 8.4%, P = 0.04). Americas (56.1%) and European (60.0%) programs were more likely to consider anonymous donors versus A/ME programs (27.7%, P = 0.01). There were no differences in consideration of complex anatomical variations. Most programs (75.9%) perform donor surgery via an open approach, and A/ME programs are more likely to use microscopic arterial reconstruction. Despite variations in practice, key aspects of living donor selection were identified. These findings provide a contemporary reference point as LDLT continues to expand into areas with limited access to liver transplantation.
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- 2021
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8. Perioperative Normal Saline Administration and Delayed Graft Function in Patients Undergoing Kidney Transplantation: A Retrospective Cohort Study
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Thomas B. Newman, Claus U. Niemann, Kerstin Kolodzie, Özlem Serpil Çakmakkaya, Mehdi Tavakol, Mi-Ok Kim, John Feiner, and Eshandeep S Boparai
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Adult ,Male ,medicine.medical_treatment ,Delayed Graft Function ,030204 cardiovascular system & hematology ,Perioperative Care ,Cohort Studies ,03 medical and health sciences ,0302 clinical medicine ,030202 anesthesiology ,medicine ,Humans ,Saline ,Dialysis ,Kidney transplantation ,Aged ,Retrospective Studies ,business.industry ,Incidence (epidemiology) ,Retrospective cohort study ,Perioperative ,Odds ratio ,Middle Aged ,medicine.disease ,Kidney Transplantation ,Anesthesiology and Pain Medicine ,Anesthesia ,Cohort ,Female ,Saline Solution ,business - Abstract
Background Perioperative normal saline administration remains common practice during kidney transplantation. The authors hypothesized that the proportion of balanced crystalloids versus normal saline administered during the perioperative period would be associated with the likelihood of delayed graft function. Methods The authors linked outcome data from a national transplant registry with institutional anesthesia records from 2005 to 2015. The cohort included adult living and deceased donor transplants, and recipients with or without need for dialysis before transplant. The primary exposure was the percent normal saline of the total amount of crystalloids administered perioperatively, categorized into a low (less than or equal to 30%), intermediate (greater than 30% but less than 80%), and high normal saline group (greater than or equal to 80%). The primary outcome was the incidence of delayed graft function, defined as the need for dialysis within 1 week of transplant. The authors adjusted for the following potential confounders and covariates: transplant year, total crystalloid volume, surgical duration, vasopressor infusions, and erythrocyte transfusions; recipient sex, age, body mass index, race, number of human leukocyte antigen mismatches, and dialysis vintage; and donor type, age, and sex. Results The authors analyzed 2,515 records. The incidence of delayed graft function in the low, intermediate, and high normal saline group was 15.8% (61/385), 17.5% (113/646), and 21% (311/1,484), respectively. The adjusted odds ratio (95% CI) for delayed graft function was 1.24 (0.85 to 1.81) for the intermediate and 1.55 (1.09 to 2.19) for the high normal saline group compared with the low normal saline group. For deceased donor transplants, delayed graft function in the low, intermediate, and high normal saline group was 24% (54/225 [reference]), 28.6% (99/346; adjusted odds ratio, 1.28 [0.85 to 1.93]), and 30.8% (277/901; adjusted odds ratio, 1.52 [1.05 to 2.21]); and for living donor transplants, 4.4% (7/160 [reference]), 4.7% (14/300; adjusted odds ratio, 1.15 [0.42 to 3.10]), and 5.8% (34/583; adjusted odds ratio, 1.66 [0.65 to 4.25]), respectively. Conclusions High percent normal saline administration is associated with delayed graft function in kidney transplant recipients. Editor’s Perspective What We Already Know about This Topic What This Article Tells Us That Is New
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- 2021
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9. Perioperative mortality in liver transplantation before and after the implementation of the organ allocation policy Share 35
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Zacharias D. Holm, Kerstin Kolodzie, Alessandro M. Galli, Christian S. Meyhoff, Claus U. Niemann, and Dieter Adelmann
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Transplantation - Abstract
In 2013, a new liver transplant allocation policy (Share 35) aimed to reduce waitlist-mortality was introduced in the United States. Regional organ sharing for recipients with a MELD score of ≥35 was prioritized over local allocation to those with lower MELD scores. Our aim was to assess the changes in perioperative mortality following the introduction of Share 35 as well as changes in patients' short-term 7-day survival, patients discharged alive and 1-year survival. Analyses were also carried out for the subgroups of patients with MELD scores ≥ and 35.We used data from the Scientific Registry of Transplant Recipients and included liver transplants between March 2002 and December 2018 in this retrospective cohort study. Perioperative mortality was defined as death during and within two days of liver transplant. We used robust interrupted time series analyses to evaluate the impact of Share 35 on mortality.We included 90 002 liver transplants in our analysis and observed a decreasing trend in perioperative mortality over time (-.061 deaths per 1000 cases per month, 95% CI -.084 to -.037, p .001). Share 35 was not associated with a change in perioperative mortality (p = .33), short-term 7-day survival (p = .48), survival to discharge (p = .56), or 1-year survival (p = .27).Prioritizing sicker recipients with a MELD score ≥35 for liver transplantation was not associated with a change in postoperative mortality.
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- 2022
10. Shared B cell memory to coronaviruses and other pathogens varies in human age groups and tissues
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Khoa D. Nguyen, Grace H. Jean, Claus U. Niemann, Katherine J. L. Jackson, Tho D. Pham, Ramona A. Hoh, Emily Haraguchi, Katharina Röltgen, Julie Parsonnet, Yi Liu, Sandra C. A. Nielsen, Fan Yang, Kari C. Nadeau, Ji-Yeun Lee, Scott D. Boyd, Krishna M. Roskin, Robert S. Ohgami, Eleanor M. Osborne, and Oliver F. Wirz
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Male ,0301 basic medicine ,Aging ,viruses ,Antibodies, Viral ,medicine.disease_cause ,Serology ,0302 clinical medicine ,Coronavirus ,Aged, 80 and over ,B-Lymphocytes ,Multidisciplinary ,Genes, Immunoglobulin ,virus diseases ,Middle Aged ,Ebolavirus ,Fetal Blood ,medicine.anatomical_structure ,Child, Preschool ,Medicine ,Female ,Antibody ,Immunoglobulin Heavy Chains ,Clone (B-cell biology) ,Adult ,Adolescent ,Immunology ,Receptors, Antigen, B-Cell ,Somatic hypermutation ,Spleen ,Cross Reactions ,Biology ,Young Adult ,03 medical and health sciences ,Report ,medicine ,Humans ,B cell ,Aged ,SARS-CoV-2 ,Infant ,Immunoglobulin D ,Immunoglobulin Class Switching ,030104 developmental biology ,Immunoglobulin M ,Immunoglobulin class switching ,biology.protein ,Lymph Nodes ,Somatic Hypermutation, Immunoglobulin ,Immunologic Memory ,Reports ,030215 immunology - Abstract
Kids armed with anti-coronavirus B cells It remains unclear whether B cell repertoires against coronaviruses and other pathogens differ between adults and children and how important these distinctions are. Yang et al. analyzed blood samples from young children and adults, as well as tissues from deceased organ donors, characterizing the B cell receptor (BCR) repertoires specific to six common pathogens and two viruses that they had not seen before: Ebola virus and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Children had higher frequencies of B cells with convergent BCR heavy chains against previously encountered pathogens and higher frequencies of class-switched convergent B cell clones against SARS-CoV-2 and related coronaviruses. These findings suggest that encounters with coronaviruses in early life may produce cross-reactive memory B cell populations that contribute to divergent COVID-19 susceptibilities. Science, this issue p. 738, Blood taken from children before the COVID-19 pandemic contains memory B cells that bind SARS-CoV-2., Vaccination and infection promote the formation, tissue distribution, and clonal evolution of B cells, which encode humoral immune memory. We evaluated pediatric and adult blood and deceased adult organ donor tissues to determine convergent antigen-specific antibody genes of similar sequences shared between individuals. B cell memory varied for different pathogens. Polysaccharide antigenspecific clones were not exclusive to the spleen. Adults had higher clone frequencies and greater class switching in lymphoid tissues than blood, while pediatric blood had abundant class-switched convergent clones. Consistent with reported serology, prepandemic children had class-switched convergent clones to severe acute respiratory syndrome coronavirus 2 with weak cross-reactivity to other coronaviruses, while adult blood or tissues showed few such clones. These results highlight the prominence of early childhood B cell clonal expansions and cross-reactivity for future responses to novel pathogens.
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- 2021
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11. Enhanced recovery for liver transplantation: recommendations from the 2022 International Liver Transplantation Society consensus conference
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Joerg M Pollok, Pascale Tinguely, Marina Berenguer, Claus U Niemann, Dimitri A Raptis, Michael Spiro, Andreas Mayr, Beatriz Dominguez, Elmi Muller, Karina Rando, Mary Anne Enoch, Noam Tamir, Pamela Healy, Tanja Manser, Tim Briggs, Abhideep Chaudhary, Abhinav Humar, Ali Jafarian, Arvinder Singh Soin, Bijan Eghtesad, Charles Miller, Daniel Cherqui, Didier Samuel, Dieter Broering, Elizabeth Pomfret, Federico Villamil, Francois Durand, Gabriela Berlakovich, Geoffrey McCaughan, Georg Auzinger, Giuliano Testa, Goran Klintmalm, Jacques Belghiti, James Findlay, Jennifer Lai, John Fung, John Klinck, John Roberts, Linda Liu, Mark Cattral, Mark Ghobrial, Markus Selzner, Michael Ramsay, Mohamed Rela, Nancy Ascher, Nancy Kwan Man, Nazia Selzner, Patrizia Burra, Peter Friend, Ronald Busuttil, Shin Hwang, Stuart McCluskey, Valeria Mas, Vijay Vohra, Vivek Vij, William Merritt, Yaman Tokat, Yoogoo Kang, Albert Chan, Alessandra Mazzola, Amelia Hessheimer, Ashwin Rammohan, Brian Hogan, Carmen Vinaixa, David Nasralla, David Victor, Eleonora De Martin, Felipe Alconchel, Garrett Roll, Gokhan Kabacam, Gonzalo Sapisochin, Isabel Campos-Varela, Jiang Liu, Madhukar S. Patel, Manhal Izzy, Marit Kalisvaart, Megan Adams, Nicholas Goldaracena, Roberto Hernandez-Alejandro, Ryan Chadha, Tamer Mahmoud Shaker, Tarunjeet S. Klair, Terry Pan, Tomohiro Tanaka, Uzung Yoon, Varvara Kirchner, Vivienne Hannon, Yee Lee Cheah, Carlo Frola, Clare Morkane, Don Milliken, Georg Lurje, Jonathan Potts, Thomas Fernandez, Adam Badenoch, Ahmed Mukhtar, Alberto Zanetto, Aldo Montano-Loza, Alfred Kow Wei Chieh, Amol Shetty, Andre DeWolf, Andrea Olmos, Anna Mrzljak, Annabel Blasi, Annalisa Berzigotti, Ashish Malik, Akila Rajakumar, Brian Davidson, Bryan O'Farrell, Camille Kotton, Charles Imber, Choon Hyuck David Kwon, Christopher Wray, Chul-Soo Ahn, Claus Krenn, Cristiano Quintini, Daniel Maluf, Daniel Santa Mina, Daniel Sellers, Deniz Balci, Dhupal Patel, Dianne LaPointe Rudow, Diethard Monbaliu, Dmitri Bezinover, Dominik Krzanicki, Dong-Sik Kim, Elizabeth Brombosz, Emily Blumberg, Emmanuel Weiss, Emmanuel Wey, Fady Kaldas, Faouzi Saliba, Gabriella Pittau, Gebhard Wagener, Gi-Won Song, Gianni Biancofiore, Gonzalo Crespo, Gonzalo Rodríguez, Graciela Martinez Palli, Gregory McKenna, Henrik Petrowsky, Hiroto Egawa, Iman Montasser, Jacques Pirenne, James Eason, James Guarrera, James Pomposelli, Jan Lerut, Jean Emond, Jennifer Boehly, Jennifer Towey, Jens G Hillingsø, Jeroen de Jonge, Juan Caicedo, Julie Heimbach, Juliet Ann Emamaullee, Justyna Bartoszko, Ka Wing Ma, Kate Kronish, Katherine T. Forkin, Kenneth Siu Ho Chok, Kim Olthoff, Koen Reyntjens, Kwang-Woong Lee, Kyung-Suk Suh, Linda Denehy, Luc J.W. van der Laan, Lucas McCormack, Lucy Gorvin, Luis Ruffolo, Mamatha Bhat, María Amalia Matamoros Ramírez, Maria-Carlota Londoño, Marina Gitman, Mark Levstik, Martin de Santibañes, Martine Lindsay, Matteo Parotto, Matthew Armstrong, Mureo Kasahara, Nick Schofield, Nicole Rizkalla, Nobuhisa Akamatsu, Olivier Scatton, Onur Keskin, Oscar Imventarza, Oya Andacoglu, Paolo Muiesan, Patricia Giorgio, Patrick Northup, Paulo Matins, Peter Abt, Philip N Newsome, Philipp Dutkowski, Pooja Bhangui, Prashant Bhangui, Puneeta Tandon, Raffaele Brustia, Raymond Planinsic, Robert Brown, Robert Porte, Rolf Barth, Rubén Ciria, Sander Florman, Sebastien Dharancy, Sher-Lu Pai, Shintaro Yagi, Silvio Nadalin, Srinath Chinnakotla, Stuart J Forbes, Suehana Rahman, Suk Kyun Hong, Sun Liying, Susan Orloff, Susan Rubman, Susumu Eguchi, Toru Ikegami, Trevor Reichman, Utz Settmacher, Varuna Aluvihare, Victor Xia, Young-In Yoon, Yuji Soejima, Yuri Genyk, Arif Jalal, Aditya Borakati, Adrian Gustar, Ahmed Mohamed, Alejandro Ramirez, Alex Rothnie, Aneya Scott, Anika Sharma, Annalise Munro, Arun Mahay, Belle Liew, Camila Hidalgo, Cara Crouch, Cheung Tsz Yan, Christoph Tschuor, Conrad Shaw, Dimitrios Schizas, Dominic Fritche, Fabia Ferdousi Huda, Gemma Wells, Giselle Farrer, Hiu Tat Kwok, Ioannis Kostakis, Joao Mestre-Costa, Ka Hay Fan, Ka Siu Fan, Kyra Fraser, Lelia Jeilani, Li Pang, Lorenzo Lenti, Manikandan Kathirvel, Marinos Zachiotis, Michail Vailas, Michele Mazza Milan, Mohamed Elnagar, Mohammad Alradhawi, Nikolaos Dimitrokallis, Nikolaos Machairas, Nolitha Morare, Oscar Yeung, Pragalva Khanal, Pranav Satish, Shahi Abdul Ghani, Shahroo Makhdoom, Sithhipratha Arulrajan, Stephanie Bogan, Stephanos Pericleous, Timon Blakemore, Vanessa Otti, Walter Lam, Whitney Jackson, and Zakee Abdi
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Consensus ,Hepatology ,Gastroenterology ,Living Donors ,Humans ,Liver Transplantation - Abstract
There is much controversy regarding enhanced recovery for recipients of liver transplants from deceased and living donors. The objectives of this Review were to summarise current knowledge on individual enhanced recovery elements on short-term outcomes, identify key components for comprehensive pathways, and create internationally accepted guidelines on enhanced recovery for liver-transplant recipients. The ERAS4OLT.org collaborative partnered by the International Liver Transplantation Society performed systematic literature reviews on the effect of 32 relevant enhanced perioperative recovery elements on short-term outcomes, and global specialists prepared expert statements on deceased and living donor liver transplantation. The Grading Recommendations, Assessment, Development and Evaluations approach was used for rating of quality of evidence and grading of recommendations. A virtual international consensus conference was held in January, 2022, in which results were presented, voted on by the audience, and discussed by an independent international jury of eight members, applying the Danish model of consensus. 273 liver transplantation specialists from 30 countries prepared expert statements on elements of enhanced recovery for liver transplantation based on the systematic literature reviews. The consensus conference yielded 80 final recommendations, covering aspects of enhanced recovery for preoperative assessment and optimisation, intraoperative surgical and anaesthetic conduct, and postoperative management for the recipients of liver transplants from both deceased and living donors, and for the living donor. The recommendations represent a comprehensive overview of the relevant elements and areas of enhanced recovery for liver transplantation. These internationally established guidelines could direct the development of enhanced recovery programmes worldwide, allowing adjustments according to local resources and practices.
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- 2022
12. The Association Between Vena Cava Implantation Technique and Acute Kidney Injury After Liver Transplantation
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Michael P. Bokoch, Anna Mello, Dieter Adelmann, Claus U. Niemann, Vivienne Hannon, John Feiner, Kathleen D. Liu, Li Zhang, Rachel Hill, Rishi Kothari, and Garrett R. Roll
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Transplantation ,medicine.medical_specialty ,Warm Ischemia Time ,business.industry ,Incidence (epidemiology) ,medicine.medical_treatment ,Urology ,Acute kidney injury ,Renal function ,Retrospective cohort study ,Odds ratio ,030230 surgery ,Liver transplantation ,urologic and male genital diseases ,medicine.disease ,03 medical and health sciences ,0302 clinical medicine ,medicine ,030211 gastroenterology & hepatology ,cardiovascular diseases ,business ,Dialysis - Abstract
BACKGROUND Acute kidney injury (AKI) after liver transplantation is associated with increased morbidity and mortality. It remains controversial whether the choice of vena cava reconstruction technique impacts AKI. METHODS This is a single-center retrospective cohort of 897 liver transplants performed between June 2009 and September 2018 using either the vena cava preserving piggyback technique or caval replacement technique without veno-venous bypass or shunts. The association between vena cava reconstruction technique and stage of postoperative AKI was assessed using multivariable ordinal logistic regression. Causal mediation analysis was used to evaluate warm ischemia time as a potential mediator of this association. RESULTS The incidence of AKI (AKI stage ≥2) within 48 h after transplant was lower in the piggyback group (40.3%) compared to the caval replacement group (51.8%, P < 0.001). Piggyback technique was associated with a reduced risk of developing a higher stage of postoperative AKI (odds ratio, 0.49; 95% confidence interval, 0.37-0.65, P < 0.001). Warm ischemia time was shorter in the piggyback group and identified as potential mediator of this effect. There was no difference in renal function (estimated glomerular filtration rate and the number of patients alive without dialysis) 1 y after transplant. CONCLUSIONS Piggyback technique, compared with caval replacement, was associated with a reduced incidence of AKI after liver transplantation. There was no difference in long-term renal outcomes between the 2 groups.
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- 2020
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13. Vasopressor selection during critical care management of brain dead organ donors and the effects on kidney graft function
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Mitchell B. Sally, Madhukar S. Patel, Margaret Katherine Ellis, Michael P. Hutchens, Elizabeth A. Swanson, Nora E. Jameson, Darren J. Malinoski, Tahnee Groat, and Claus U. Niemann
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Adult ,Male ,Brain Death ,medicine.medical_specialty ,Tissue and Organ Procurement ,Critical Care ,medicine.medical_treatment ,Urology ,Delayed Graft Function ,Kidney ,Critical Care and Intensive Care Medicine ,Risk Assessment ,Cold Ischemia Time ,Article ,Phenylephrine ,Young Adult ,03 medical and health sciences ,chemistry.chemical_compound ,0302 clinical medicine ,medicine ,Humans ,Vasoconstrictor Agents ,Prospective Studies ,Prospective cohort study ,Dialysis ,Univariate analysis ,Creatinine ,Dose-Response Relationship, Drug ,business.industry ,Cold Ischemia ,Age Factors ,030208 emergency & critical care medicine ,Middle Aged ,Kidney Transplantation ,Transplantation ,medicine.anatomical_structure ,chemistry ,Female ,Surgery ,business ,medicine.drug - Abstract
BACKGROUND: Delayed graft function (DGF), the need for dialysis in the first week following kidney transplant, affects approximately one-quarter of deceased-donor kidney transplant recipients. Donor demographics, donor serum creatinine, and graft cold ischemia time are associated with DGF. However, there is no consensus on the optimal management of hemodynamic instability in organ donors after brain death (DBDs). Our objective was to determine the relationship between vasopressor selection during donor management and the development of DGF. METHODS: Prospective observational data, including demographic and critical care parameters, were collected for all DBDs managed by seventeen Organ Procurement Organizations from nine Organ Procurement and Transplantation Network Regions between 2012 and 2018. Recipient outcome data were linked with donor data through donor identification numbers. Donor critical care parameters, including type of vasopressor and doses, were recorded at three standardized time points during donor management. The analysis included only donors who received at least one vasopressor at all three time points. Vasopressor doses were converted to norepinephrine equivalent doses and analyzed as continuous variables. Univariate analyses were conducted to determine the association between donor variables and DGF. Results were adjusted for known predictors of DGF using binary logistic regression. RESULTS: Complete data were available for 5,554 kidney transplant recipients and 2,985 DBDs. On univariate analysis, donor serum creatinine, donor age, donor subtype, kidney donor profile index, graft cold ischemia time, phenylephrine dose, and dopamine dose were associated with DGF. After multivariable analysis, increased donor serum creatinine, donor age, kidney donor profile index, graft cold ischemia time, and phenylephrine dose remained independent predictors of DGF. CONCLUSION: Higher doses of phenylephrine were an independent predictor of DGF. With the exception of phenylephrine, the selection and dose of vasopressor during donor management did not predict the development of DGF. LEVEL OF EVIDENCE: Prognostic study, level III
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- 2020
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14. P2.02: Save the Environment: Liver Transplantation Restores A Circulating Environment That Supports Healthy Platelet Aggregation Within Two Hours of Reperfusion
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Hillary Braun, Alex T Fields, Kim Rodriguez, Zachary A Matthay, Rishi Kothari, Claus U Niemann, Dieter Adelmann, Nancy L Ascher, John P Roberts, Michael P Bokoch, and Lucy Z Kornblith
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Transplantation - Published
- 2022
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15. Expedited evaluation for liver transplantation: A critical look at processes and outcomes
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Hillary J. Braun, Anna Mello, Rishi Kothari, Mignote Yilma, Elaine Ku, Claus U. Niemann, Li Zhang, Mehdi Tavakol, Dieter Adelmann, and Nancy L. Ascher
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organ allocation ,liver allograft function ,medicine.medical_specialty ,Kidney Disease ,medicine.medical_treatment ,Clinical Trials and Supportive Activities ,Clinical Sciences ,Renal and urogenital ,Patient characteristics ,Liver transplantation ,Living donor ,Article ,Disease severity ,Clinical Research ,Risk Factors ,Internal medicine ,Risk index ,Living Donors ,medicine ,Overall survival ,Humans ,patient characteristics ,Retrospective Studies ,Transplantation ,dysfunction ,business.industry ,Liver Disease ,Graft Survival ,Patient survival ,Organ Transplantation ,Transplant Recipients ,Liver Transplantation ,Good Health and Well Being ,Treatment Outcome ,Increased risk ,liver allograft function / dysfunction ,Surgery ,Digestive Diseases ,business - Abstract
BACKGROUND Most patients are listed for liver transplant (LT) following extensive workup as outpatients ("conventional evaluation"). Some patients undergo urgent evaluation as inpatients after being transferred to a transplant center ("expedited evaluation"). We hypothesized that expedited patients would have inferior survival due to disease severity at the time of transplant and shorter workup time. METHODS Patients who underwent evaluation for LT at our institution between 2012-2016 were retrospectively reviewed. The expedited and conventional cohorts were defined as above. Living donor LT recipients, combined liver-kidney recipients, acute liver failure patients, and re-transplant patients were excluded. We compared patient characteristics and overall survival between patients who received a transplant following expedited evaluation and those who did not, and between LT recipients based on expedited or conventional evaluation. RESULTS 509 patients were included (110 expedited, 399 conventional). There was no difference in graft or patient survival at one year for expedited versus conventional LT recipients. In multivariable analysis of overall survival, only Donor Risk Index (HR 1.97, CI 1.04-3.73, p = 0.037, per unit increase) was associated with increased risk of death. CONCLUSIONS Patients who underwent expedited evaluation for LT had significant demographic and clinical differences from patients who underwent conventional evaluation, but comparable post-transplant survival. This article is protected by copyright. All rights reserved.
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- 2021
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16. Organ donor management goals and delayed graft function in adult kidney transplant recipients
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Darren Malinoski, Claus U. Niemann, Dieter Adelmann, Rishi Kothari, Roger J. Lewis, and Juliana Tolles
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Adult ,medicine.medical_specialty ,Population ,Delayed Graft Function ,Logistic regression ,Kidney transplant ,Risk Factors ,Internal medicine ,medicine ,Humans ,Imputation (statistics) ,education ,Donor management ,Kidney transplantation ,Retrospective Studies ,Transplantation ,education.field_of_study ,Kidney ,business.industry ,Graft Survival ,medicine.disease ,Kidney Transplantation ,Tissue Donors ,medicine.anatomical_structure ,Case-Control Studies ,business ,Goals - Abstract
BACKGROUND Delayed graft function (DGF) after kidney transplantation is a common occurrence and correlates with poor graft and patient outcomes. Donor characteristics and care are known to impact DGF. We attempted to show the relationship between achievement of specific donor management goals (DMG) and DGF. METHODS This is a retrospective case-control study using data from 14 046 adult kidney donations after brain death from hospitals in 18 organ procurement organizations (OPOs) which were transplanted to adult recipients between 2012 and 2018. Data on DMG compliance and donor, recipient, and ischemia-related factors were used to create multivariable logistic regression models. RESULTS The overall rate of DGF was 29.4%. Meeting DMGs for urine output and vasopressor use were associated with decreased risk of DGF. Sensitivity analyses performed with different imputation methods, omitting recipient factors, and analyzing multiple time points yielded largely consistent results. CONCLUSIONS The development of DMGs continues to show promise in improving outcomes in the kidney transplant recipient population. Studies have already shown increased kidney utilization in smaller cohorts, as well as other organs, and shown decreased rates of DGF. Additional research and analysis are required to assess interactions between meeting DMGs and correlation versus causality in DMGs and DGF.
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- 2021
17. Raster Thomson scattering in large-scale laser plasmas produced at high repetition rate
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R. S. Dorst, Claus U. Niemann, P. V. Heuer, Carmen Constantin, M. Kaloyan, S. Ghazaryan, Derek Schaeffer, and Jessica Pilgram
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Physics ,Electron density ,Physics - Instrumentation and Detectors ,Thomson scattering ,business.industry ,Scattering ,FOS: Physical sciences ,Instrumentation and Detectors (physics.ins-det) ,Plasma ,Laser ,Spectral line ,Physics - Plasma Physics ,law.invention ,Plasma Physics (physics.plasm-ph) ,symbols.namesake ,Optics ,law ,Calibration ,symbols ,business ,Instrumentation ,Raman scattering - Abstract
We present optical Thomson scattering measurements of electron density and temperature in a large-scale (~2 cm) exploding laser plasma produced by irradiating a solid target with a high energy (5-10 J) laser pulse at high repetition rate (1 Hz). The Thomson scattering diagnostic matches this high repetition rate. Unlike previous work performed in single shots at much higher energies, the instrument allows point measurements anywhere inside the plasma by automatically translating the scattering volume using motorized stages as the experiment is repeated at 1 Hz. Measured densities around 4$\times 10^{16}$ cm$^{-3}$ and temperatures around 7 eV result in a scattering parameter near unity, depending on the distance from the target. The measured spectra show the transition from collective scattering close to the target to non-collective scattering at larger distances. Densities obtained by fitting the weakly collective spectra agree to within 10% with an irradiance calibration performed via Raman scattering in nitrogen.
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- 2021
18. Machine Learning Prediction of Liver Allograft Utilization From Deceased Organ Donors Using the National Donor Management Goals Registry
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Dmytro Lituiev, Rishi Kothari, Jacob D Nudel, Dieter Adelmann, Ryutaro Hirose, Darren Malinoski, Claus U. Niemann, Andrew M. Bishara, Dexter Hadley, and Mitchell B. Sally
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Transplantation ,Receiver operating characteristic ,RD1-811 ,business.industry ,Liver Disease ,Chronic Liver Disease and Cirrhosis ,Authorization ,Organ Transplantation ,Machine learning ,computer.software_genre ,Liver graft ,Test set ,Early prediction ,Organ Donation and Procurement ,ComputingMethodologies_DOCUMENTANDTEXTPROCESSING ,Medicine ,Surgery ,Gradient boosting ,Artificial intelligence ,business ,Digestive Diseases ,Donor management ,computer - Abstract
Supplemental Digital Content is available in the text., Background. Early prediction of whether a liver allograft will be utilized for transplantation may allow better resource deployment during donor management and improve organ allocation. The national donor management goals (DMG) registry contains critical care data collected during donor management. We developed a machine learning model to predict transplantation of a liver graft based on data from the DMG registry. Methods. Several machine learning classifiers were trained to predict transplantation of a liver graft. We utilized 127 variables available in the DMG dataset. We included data from potential deceased organ donors between April 2012 and January 2019. The outcome was defined as liver recovery for transplantation in the operating room. The prediction was made based on data available 12–18 h after the time of authorization for transplantation. The data were randomly separated into training (60%), validation (20%), and test sets (20%). We compared the performance of our models to the Liver Discard Risk Index. Results. Of 13 629 donors in the dataset, 9255 (68%) livers were recovered and transplanted, 1519 recovered but used for research or discarded, 2855 were not recovered. The optimized gradient boosting machine classifier achieved an area under the curve of the receiver operator characteristic of 0.84 on the test set, outperforming all other classifiers. Conclusions. This model predicts successful liver recovery for transplantation in the operating room, using data available early during donor management. It performs favorably when compared to existing models. It may provide real-time decision support during organ donor management and transplant logistics.
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- 2021
19. Enhanced recovery after surgery programs improve short-term outcomes after liver transplantation-A systematic review and meta-analysis
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Dimitri A. Raptis, Pascale Tinguely, Marina Berenguer, Joerg M. Pollok, Claus U. Niemann, Alejandro Ramirez-Del Val, Nolitha Morare, and Michael Spiro
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Transplantation ,medicine.medical_specialty ,Hospital readmission ,business.industry ,medicine.medical_treatment ,Retrospective cohort study ,Liver transplantation ,Length of Stay ,Intensive care unit ,law.invention ,Liver Transplantation ,Postoperative Complications ,Randomized controlled trial ,law ,Meta-analysis ,Emergency medicine ,Medicine ,Humans ,Prospective Studies ,business ,Grading (education) ,Enhanced Recovery After Surgery ,Enhanced recovery after surgery ,Retrospective Studies - Abstract
This systematic review aimed to investigate the available quality of evidence (QOE) of enhanced recovery after surgery (ERAS) for liver transplantation (LT) on short-term outcomes, grade recommendations, and identify relevant components for ERAS protocols. A systematic review and meta-analysis were conducted on short-term outcomes after LT when applying comprehensive ERAS protocols (> 1 ERAS component) versus control groups (CRD42021210374), following the GRADE approach for grading QOE and strength of recommendations. Endpoints were morbidity, mortality, length of stay, and readmission rates after ERAS for LT. Of 858 screened articles, two randomized controlled trials, two prospective, and one retrospective cohort studies were included (2002-2020). Frequent ERAS components were early extubation and postoperative antibiotic, fluid, and nutrition management. Overall complications were reduced in ERAS versus control cohorts (OR .4 (CI .2, .7), with no significant differences in mortality and hospital readmission rates. Intensive care unit and hospital length of stay were shorter in ERAS groups (percentage decrease, 55% and 29%, respectively). QOE for individual outcomes was rated moderate to low. ERAS protocols in LT are related to improved short-term outcomes after LT (QOE; Moderate to low | Grade of Recommendation; Strong), but currently lack standardization.
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- 2021
20. Epigenomic profiling of stem cells within the pilosebaceous unit identifies PRDM16 as a regulator of sebaceous gland homeostasis
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Claus U. Niemann, Mantellato G, Alvaro Rada-Iglesias, Tore Bleckwehl, Carien M. Niessen, Rizwan Rehimi, Chacón-Martínez Ca, Sara A. Wickström, Gözüm G, Giuliano Crispatzu, and Mathieu Clément-Ziza
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Sebaceous gland ,PRDM16 ,integumentary system ,Epidermis (botany) ,Regulator ,Sebaceous hyperplasia ,Biology ,medicine.disease ,Hair follicle ,Cell biology ,medicine.anatomical_structure ,medicine ,Stem cell ,Homeostasis - Abstract
The epidermis consists of different compartments such as the hair follicle (HF), sebaceous gland (SG) and interfollicular epidermis (IFE), each containing distinct stem cell (SC) populations. However, with the exception of the SCs residing within the HF bulge, other epidermal SC populations remain less well understood. Here we used an epigenomic strategy that combines H3K27me3 ChIP-seq and RNA-seq profiling to identify major regulators of pilosebaceous unit (PSU) SC located outside the bulge. When applied to the bulk of PSU SC isolated from mouse skin our approach identified both previously known and potentially novel non-bulge PSU SC regulators. Among the latter, we found that PRDM16 was predominantly enriched within the Junctional Zone (JZ), which harbors SC that contribute to renewal of the upper HF and the SG. To investigate PRDM16 function in the PSU SC, we generated an epidermal-specific Prdm16 Knock-out mouse model (K14-Cre-Prdm16fl/fl). Notably, SG homeostasis was disturbed upon loss of PRDM16 resulting in enlarged SGs, and excessive sebum production, resembling some of the features associated with human acne and sebaceous hyperplasia. Importantly, PRDM16 is essential to shut down proliferation in differentiating sebocytes. Overall, our study provides a list of putative novel regulators of PSU SC outside the bulge and identifies PRDM16 as a major regulator of SG homeostasis.
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- 2021
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21. Shared B cell memory to coronaviruses and other pathogens varies in human age groups and tissues
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Eleanor M. Osborne, Ji-Yeun Lee, Claus U. Niemann, Robert S. Ohgami, Scott D. Boyd, Tho D. Pham, Katherine J. L. Jackson, Sandra C. A. Nielsen, Julie Parsonnet, Yi Liu, Fan Yang, Krishna M. Roskin, and Ramona A. Hoh
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Vaccination ,medicine.anatomical_structure ,biology ,Immunity ,Immunology ,medicine ,biology.protein ,Spleen ,Antibody ,Gene ,Immunoglobulin D ,B cell ,Serology - Abstract
Vaccination and infection promote the formation, tissue distribution, and clonal evolution of B cells encoding humoral immune memory. We evaluated convergent antigen-specific antibody genes of similar sequences shared between individuals in pediatric and adult blood, and deceased organ donor tissues. B cell memory varied for different pathogens. Polysaccharide antigen-specific clones were not exclusive to the spleen. Adults’ convergent clones often express mutated IgM or IgD in blood and are class-switched in lymphoid tissues; in contrast, children have abundant class-switched convergent clones in blood. Consistent with serological reports, pre-pandemic children had class-switched convergent clones to SARS-CoV-2, enriched in cross-reactive clones for seasonal coronaviruses, while adults showed few such clones in blood or lymphoid tissues. These results extend age-related and anatomical mapping of human humoral pathogen-specific immunity.One Sentence SummaryChildren have elevated frequencies of pathogen-specific class-switched memory B cells, including SARS-CoV-2-binding clones.
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- 2020
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22. Longer Distance From Dialysis Facility to Transplant Center Is Associated With Lower Access to Kidney Transplantation
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Claus U. Niemann, Adrian M Whelan, Dieter Adelmann, Elaine Ku, Kirsten L. Johansen, Charles E. McCulloch, Garrett R. Roll, Barbara Grimes, and Salpi Siyahian
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Pediatrics ,medicine.medical_specialty ,Kidney Disease ,medicine.medical_treatment ,Renal and urogenital ,lcsh:Surgery ,030230 surgery ,03 medical and health sciences ,0302 clinical medicine ,medicine ,In patient ,Center (algebra and category theory) ,Dialysis facility ,Dialysis ,Kidney transplantation ,Transplantation ,business.industry ,Retrospective cohort study ,Organ Transplantation ,lcsh:RD1-811 ,medicine.disease ,Kidney Transplantation ,Confidence interval ,030211 gastroenterology & hepatology ,business - Abstract
Author(s): Whelan, Adrian M; Johansen, Kirsten L; McCulloch, Charles E; Adelmann, Dieter; Niemann, Claus U; Roll, Garrett R; Siyahian, Salpi; Grimes, Barbara; Ku, Elaine | Abstract: Rates of kidney transplantation vary substantially across dialysis facilities in the United States. Whether distance between the dialysis facility and transplant center associates with variations in transplantation rates has not been examined.MethodsWe performed a retrospective study of adults treated with dialysis between 2005 and 2015, according to the US Renal Data System. We examined the association between distance from dialysis facility to transplant center and time to kidney transplantation (primary outcome) and waitlist registration (secondary outcome) using Fine-Gray models. We also performed sensitivity analyses using the distance from each patient's dialysis facility to the nearest transplant center as the predictor so that patients who were never registered on the waitlist (and therefore would not have a transplant center) could be included.ResultsIn total, 178 885 waitlisted patients were included for our primary analysis. As distance between dialysis facility and transplant center increased, lower hazard of transplantation (subhazard ratio [HR], 0.92; 95% confidence interval [CI], 0.91-0.94, if distance was 10 to l50 miles; sub-HR, 0.90; 95% CI, 0.88-0.92, if distance ≥50 miles compared with l10 miles) was noted. We also found a weak association between longer distance and hazard of waitlist registration (sub-HR, 0.96; 95% CI, 0.94-0.97, if distance was ≥50 miles versus l10 miles). Findings were similar in sensitivity analyses using distance between dialysis facility and the nearest transplant center (N = 1 149 721).ConclusionsPatients receiving dialysis in facilities located further away from transplant centers have lower hazard of kidney transplantation. Developing strategies to address barriers to transplantation in patients receiving dialysis at facilities located far away from a transplant center may help improve disparities in transplantation rates.
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- 2020
23. Senolytics prevent mt-DNA-induced inflammation and promote the survival of aged organs following transplantation
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Friederike Martin, Stefan G. Tullius, Markus Quante, Yeqi Nian, James L. Kirkland, Koichiro Minami, Timm Heinbokel, Claus U. Niemann, Christine S. Falk, Midas Seyda, Tamara Tchkonia, Haruhito Azuma, Jasper Iske, Abdallah Elkhal, João F. Passos, and Ryoichi Maenosono
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Male ,0301 basic medicine ,Aging ,Cellular differentiation ,Dasatinib ,General Physics and Astronomy ,02 engineering and technology ,Organ transplantation ,lcsh:Science ,Cellular Senescence ,Multidisciplinary ,Immunogenicity ,Cell Differentiation ,Middle Aged ,021001 nanoscience & nanotechnology ,Tissue Donors ,surgical procedures, operative ,Mice, Inbred DBA ,Reperfusion Injury ,Cytokines ,Quercetin ,medicine.symptom ,0210 nano-technology ,Cell-Free Nucleic Acids ,Adult ,medicine.medical_specialty ,Science ,Ischemia ,Inflammation ,DNA, Mitochondrial ,General Biochemistry, Genetics and Molecular Biology ,03 medical and health sciences ,Immune system ,medicine ,Animals ,Humans ,business.industry ,Dendritic Cells ,Organ Transplantation ,General Chemistry ,medicine.disease ,Mice, Inbred C57BL ,Transplantation ,030104 developmental biology ,Immunology ,Heart Transplantation ,lcsh:Q ,business ,Reperfusion injury - Abstract
Older organs represent an untapped potential to close the gap between demand and supply in organ transplantation but are associated with age-specific responses to injury and increased immunogenicity, thereby aggravating transplant outcomes. Here we show that cell-free mitochondrial DNA (cf-mt-DNA) released by senescent cells accumulates with aging and augments immunogenicity. Ischemia reperfusion injury induces a systemic increase of cf-mt-DNA that promotes dendritic cell-mediated, age-specific inflammatory responses. Comparable events are observed clinically, with the levels of cf-mt-DNA elevated in older deceased organ donors, and with the isolated cf-mt-DNA capable of activating human dendritic cells. In experimental models, treatment of old donor animals with senolytics clear senescent cells and diminish cf-mt-DNA release, thereby dampening age-specific immune responses and prolonging the survival of old cardiac allografts comparable to young donor organs. Collectively, we identify accumulating cf-mt-DNA as a key factor in inflamm-aging and present senolytics as a potential approach to improve transplant outcomes and availability. Organ transplantation involving aged donors is often confounded by reduced post-transplantation organ survival. By studying both human organs and mouse transplantation models, here the authors show that pretreating the donors with senolytics to reduce mitochondria DNA and pro-inflammatory dendritic cells may help promote survival of aged organs.
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- 2020
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24. Prospective Multicenter Study of Early Antiviral Therapy in Liver and Kidney Transplant Recipients of HCV-Viremic Donors
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David W. Victor, Norah A. Terrault, Sumit Mohan, Raymond A. Rubin, Claus U. Niemann, Jennifer L. Dodge, Mark Ghobrial, Elizabeth C. Verna, James F. Trotter, Johanna Bayer, James R. Burton, and Christina Klein
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0301 basic medicine ,Male ,medicine.medical_specialty ,Sustained Virologic Response ,Hepatitis C virus ,Cardiomyopathy ,Renal function ,Viremia ,Hepacivirus ,medicine.disease_cause ,Kidney ,Gastroenterology ,Antiviral Agents ,Heterocyclic Compounds, 4 or More Rings ,Proof of Concept Study ,Drug Administration Schedule ,03 medical and health sciences ,0302 clinical medicine ,Interquartile range ,Internal medicine ,Medicine ,Humans ,Prospective Studies ,Adverse effect ,Hepatology ,business.industry ,Middle Aged ,Viral Load ,medicine.disease ,Hepatitis C ,Kidney Transplantation ,Tissue Donors ,Transplant Recipients ,Discontinuation ,Liver Transplantation ,030104 developmental biology ,medicine.anatomical_structure ,Liver ,Linear Models ,030211 gastroenterology & hepatology ,Female ,Carbamates ,Sofosbuvir ,business - Abstract
Background and aims Organs from hepatitis C virus (HCV)-viremic donors have been used in HCV-uninfected recipients (D+/R-), but the optimal treatment approach has not been defined. We evaluated the kinetics of HCV infection following transplant in D+/R- kidney-transplant (KT) and liver-transplant (LT) recipients when a preemptive antiviral strategy was used. Approach and results Six US transplant programs prospectively treated D+/R- primary LT and KT recipients with sofosbuvir-velpastasvir for 12 weeks starting once viremia was confirmed following transplant and the patients were judged to be clinically stable, including estimated glomerular filtration rate >30 mL/min. Primary endpoints were sustained virologic response at 12 weeks following transplant and safety (assessed by proportion of treatment-related adverse and serious adverse events). Of the 24 patients transplanted (13 liver, of whom 2 had prior-treated HCV infection; 11 kidney), 23 became viremic after transplant. The median (interquartile range) time from transplant to start of antiviral therapy was 7.0 (6.0, 12.0) versus 16.5 (9.8, 24.5) days, and the median (interquartile range) HCV-RNA level 3 days after transplant was 6.5 (3.9, 7.1) versus 3.6 (2.9, 4.0) log10 IU/mL in LT versus KT recipients, respectively. By week 4 of treatment, 10 of 13 (77%) LT, but only 2 of 10 (20%) KT, had undetectable HCV RNA (P = 0.01). At the end of treatment, all LT recipients were HCV RNA-undetectable, whereas 3 (30%) of the kidney recipients still had detectable, but not quantifiable, viremia. All achieved sustained virologic response at 12 weeks following transplant (lower 95% confidence interval bound: 85%). Serious adverse events considered possibly related to treatment were antibody-mediated rejection, biliary sclerosis, cardiomyopathy, and graft-versus-host disease, with the latter associated with multiorgan failure, premature treatment discontinuation, and death. Conclusions Despite differing kinetics of early HCV infection in liver versus non-liver recipients, a preemptive antiviral strategy is effective. Vigilance for adverse immunologic events is warranted.
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- 2020
25. COVID-19 and Abdominal Transplant: A Stepwise Approach to Practice During Pandemic Conditions
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Jun Shoji, Anna Mello, Hillary J. Braun, Claus U. Niemann, Andrew M. Posselt, Francis Y. Yao, Chris E. Freise, Allison B. Webber, Garrett R. Roll, Nancy L. Ascher, Neil Mehta, James M. Gardner, Dieter Adelmann, Sang-Mo Kang, Ryutaro Hirose, Shareef Syed, Peter G. Stock, Sandy Feng, and John P. Roberts
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2019-20 coronavirus outbreak ,Psychoanalysis ,Coronavirus disease 2019 (COVID-19) ,Waiting Lists ,Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) ,Pneumonia, Viral ,030230 surgery ,Medical and Health Sciences ,Vaccine Related ,03 medical and health sciences ,Betacoronavirus ,0302 clinical medicine ,Biodefense ,Pandemic ,Humans ,Sociology ,Viral ,Lung ,Pandemics ,Immunosuppression Therapy ,Transplantation ,SARS-CoV-2 ,Prevention ,Medical practice ,COVID-19 ,Pneumonia ,Organ Transplantation ,Original Clinical Science—General ,Tissue Donors ,Emerging Infectious Diseases ,Infectious Diseases ,Good Health and Well Being ,Practice Guidelines as Topic ,Pneumonia & Influenza ,Health Resources ,030211 gastroenterology & hepatology ,Surgery ,Severe acute respiratory syndrome coronavirus ,Coronavirus Infections ,Stepwise approach ,Immunosuppression - Abstract
Author(s): Syed, Shareef M; Gardner, James; Roll, Garrett; Webber, Allison; Mehta, Neil; Shoji, Jun; Adelmann, Dieter; Niemann, Claus; Braun, Hillary J; Mello, Anna; Yao, Francis; Posselt, Andrew; Kang, Sang-Mo; Hirose, Ryutaro; Roberts, John; Feng, Sandy; Ascher, Nancy; Stock, Peter; Freise, Chris | Abstract: BackgroundThe novel severe acute respiratory syndrome coronavirus (SARS-CoV-2) disease has transformed innumerable aspects of medical practice, particularly in the field of transplantation.Main bodyHere we describe a single-center approach to creating a generalizable, comprehensive, and graduated set of recommendations to respond in stepwise fashion to the challenges posed by these conditions, and the underlying principles guiding such decisions.ConclusionsCreation of a stepwise plan will allow transplant centers to respond in a dynamic fashion to the ongoing challenges posed by the COVID-19 pandemic.
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- 2020
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26. The Association Between Vena Cava Implantation Technique and Acute Kidney Injury After Liver Transplantation
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Vivienne, Hannon, Rishi P, Kothari, Li, Zhang, Michael P, Bokoch, Rachel, Hill, Garrett R, Roll, Anna, Mello, John R, Feiner, Kathleen D, Liu, Claus U, Niemann, and Dieter, Adelmann
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Male ,Time Factors ,Incidence ,Graft Survival ,Vena Cava, Inferior ,Acute Kidney Injury ,Middle Aged ,Risk Assessment ,Liver Transplantation ,Treatment Outcome ,Risk Factors ,Humans ,Female ,Warm Ischemia ,Vascular Surgical Procedures ,Glomerular Filtration Rate ,Retrospective Studies - Abstract
Acute kidney injury (AKI) after liver transplantation is associated with increased morbidity and mortality. It remains controversial whether the choice of vena cava reconstruction technique impacts AKI.This is a single-center retrospective cohort of 897 liver transplants performed between June 2009 and September 2018 using either the vena cava preserving piggyback technique or caval replacement technique without veno-venous bypass or shunts. The association between vena cava reconstruction technique and stage of postoperative AKI was assessed using multivariable ordinal logistic regression. Causal mediation analysis was used to evaluate warm ischemia time as a potential mediator of this association.The incidence of AKI (AKI stage ≥2) within 48 h after transplant was lower in the piggyback group (40.3%) compared to the caval replacement group (51.8%, P0.001). Piggyback technique was associated with a reduced risk of developing a higher stage of postoperative AKI (odds ratio, 0.49; 95% confidence interval, 0.37-0.65, P0.001). Warm ischemia time was shorter in the piggyback group and identified as potential mediator of this effect. There was no difference in renal function (estimated glomerular filtration rate and the number of patients alive without dialysis) 1 y after transplant.Piggyback technique, compared with caval replacement, was associated with a reduced incidence of AKI after liver transplantation. There was no difference in long-term renal outcomes between the 2 groups.
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- 2020
27. Contributors
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Gaurav Agarwal, Talal M. Al-Qaoud, Barbara D. Alexander, Richard D.M. Allen, Frederike Ambagtsheer, Rolf N. Barth, Amit Basu, Tomas Castro-Dopico, Eileen T. Chambers, Jeremy R. Chapman, Menna R. Clatworthy, Bradley Henry Collins, Robert B. Colvin, Lynn D. Cornell, Sylvia F. Costa, Alice Crane, Andrew Davenport, Matthew J. Ellis, Brian Ezekian, Casey Victoria Farin, Alton B. Farris, Jay A. Fishman, Sander Florman, MD, John L.R. Forsythe, Peter J. Friend, Susan V. Fuggle, Rouba Garro, Robert S. Gaston, Edward K. Geissler, Sommer Elizabeth Gentry, James A. Gilbert, David Hamilton, Reem E. Hamoda, Benson M. Hoffman, Matthew L. Holzner, Joanna Hooten, James P. Hunter, Alan G. Jardine, Laura S. Johnson, Arman A. Kahokehr, Dixon B. Kaufman, Karen L. Keung, Allan D. Kirk, Stuart J. Knechtle, Simon R. Knight, Kate Kronish, John C. LaMattina, Jennifer S. Lees, Henri Leuvenink, Jayme E. Locke, Michael R. Lucey, Matthew William Luedke, Anne Louise Marano, Lorna P. Marson, Chantal Mathieu, Madhav C. Menon, Sir Peter J. Morris, Elmi Muller, Barbara Murphy, Sarah A. Myers, Brian J. Nankivell, Claus U. Niemann, John O’Callaghan, Philip John O’Connell, Jon S. Odorico, Andrea Olmos, Gabriel Oniscu, Rachel E. Patzer, Liset H.M. Pengel, Andrew C. Peterson, Jacques Pirenne, Rutger J. Ploeg, Brenda Maria Rosales, Nasia Safdar, MD, Adnan Said, Caroline K. Saulino, Carrie Schinstock, Paul M. Schroder, Dorry L. Segev, Ron Shapiro, Daniel A. Shoskes, Patrick J. Smith, Ben Sprangers, Mark Stegall, Ram M. Subramanian, Craig J. Taylor, John F. Thompson, Vikram Wadhera, Mark Waer, Christopher J.E. Watson, Angela Claire Webster, Willem Weimar, Pamela D. Winterberg, Kathryn J. Wood, and Diana A. Wu
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- 2020
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28. Weighing the waitlist: Weight changes and access to kidney transplantation among obese candidates
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Elaine Ku, Kirsten L. Johansen, Garrett R. Roll, Adrian M Whelan, Brian Lee, Barbara Grimes, Claus U. Niemann, Charles E. McCulloch, and Dor, Frank JMF
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Male ,Kidney Disease ,Physiology ,medicine.medical_treatment ,030232 urology & nephrology ,030230 surgery ,Weight Gain ,Body Mass Index ,Kidney Failure ,0302 clinical medicine ,Weight loss ,Medicine and Health Sciences ,Renal Transplantation ,Ethnicities ,Chronic ,Hispanic People ,Kidney transplantation ,Multidisciplinary ,Hispanic or Latino ,Middle Aged ,Physiological Parameters ,Nephrology ,Medicine ,Female ,medicine.symptom ,Hispanic Americans ,Research Article ,Adult ,medicine.medical_specialty ,Waiting Lists ,General Science & Technology ,Science ,European Continental Ancestry Group ,Renal and urogenital ,Surgical and Invasive Medical Procedures ,Urinary System Procedures ,White People ,03 medical and health sciences ,Clinical Research ,Internal medicine ,Weight Loss ,Medical Dialysis ,medicine ,Humans ,Obesity ,Dialysis ,Nutrition ,Aged ,Transplantation ,Whites ,business.industry ,Prevention ,Body Weight ,Biology and Life Sciences ,Organ Transplantation ,medicine.disease ,Kidney Transplantation ,People and Places ,Kidney Failure, Chronic ,Population Groupings ,business ,Body mass index ,Weight gain ,Kidney disease - Abstract
High body mass index is a known barrier to access to kidney transplantation in patients with end-stage kidney disease. The extent to which weight and weight changes affect access to transplantation among obese candidates differentially by race/ethnicity has received little attention. We included 10 221 obese patients waitlisted for kidney transplantation prior to end-stage kidney disease onset between 1995–2015. We used multinomial logistic regression models to examine the association between race/ethnicity and annualized change in body mass index (defined as stable [-2 to 2 kg/m2/year], loss [>2 kg/m2/year] or gain [>2 kg/m2/year]). We then used Fine-Gray models to examine the association between weight changes and access to living or deceased donor transplantation by race/ethnicity, accounting for the competing risk of death. Overall, 29% of the cohort lost weight and 7% gained weight; 46% received a transplant. Non-Hispanic blacks had a 24% (95% CI 1.12–1.38) higher odds of weight loss and 22% lower odds of weight gain (95% CI 0.64–0.95) compared with non-Hispanic whites. Hispanics did not differ from whites in their odds of weight loss or weight gain. Overall, weight gain was associated with lower access to transplantation (HR 0.88 [95% CI 0.79–0.99]) compared with maintenance of stable weight, but weight loss was not associated with better access to transplantation (HR 0.96 [95% CI 0.90–1.02]), although this relation differed by baseline body mass index and for recipients of living versus deceased donor organs. For example, weight loss was associated with improved access to living donor transplantation (HR 1.24 [95% CI 1.07–1.44]) in whites but not in blacks or Hispanics. In a cohort of obese patients waitlisted before dialysis, blacks were more likely to lose weight and less likely to gain weight compared with whites. Weight loss was only associated with improved access to living donor transplantation among whites. Further studies are needed to understand the reasons for the observed associations.
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- 2020
29. The Impact of Deceased Donor Liver Extraction Time on Early Allograft Function in Adult Liver Transplant Recipients
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Shareef Syed, Mehdi Tavakol, Dieter Adelmann, Rishi Kothari, Claus U. Niemann, Garrett R. Roll, and Lyle Burdine
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Adult ,Male ,medicine.medical_specialty ,Time Factors ,medicine.medical_treatment ,Operative Time ,030230 surgery ,Liver transplantation ,Risk Assessment ,Graft function ,Decision Support Techniques ,03 medical and health sciences ,0302 clinical medicine ,Liver Function Tests ,Predictive Value of Tests ,Risk Factors ,medicine ,Hepatectomy ,Humans ,Warm Ischemia ,Transplantation ,Deceased donor ,medicine.diagnostic_test ,business.industry ,Cold Ischemia ,Graft Survival ,Middle Aged ,Warm ischemia ,Tissue Donors ,Liver Transplantation ,Surgery ,Treatment Outcome ,Initial phase ,Tissue and Organ Harvesting ,Operative time ,Female ,030211 gastroenterology & hepatology ,Adult liver ,Primary Graft Dysfunction ,business ,Liver function tests - Abstract
In liver transplantation, both cold and warm ischemia times are known to impact early graft function. The extraction time is a period during the initial phase of organ cooling which occurs during deceased donor procurement. During this time, the organ is at risk of suboptimal cooling. Whether donor extraction time, the time from donor aortic cross-clamp to removal of the donor organ from the body cavity has an effect on early graft function is not known.We investigated the effect of donor extraction time on early graft function in 292 recipients of liver grafts procured locally and transplanted at our center between June 2012 and December 2016. Early graft function was assessed using the model of early allograft function score in a multivariable regression model including donor extraction time, cold ischemia time, warm ischemia time, donor risk index, and terminal donor sodium.Donor extraction time had an independent effect on early graft function measured by the model of early allograft function score (coefficient, 0.021; 95% confidence interval, 0.007-0.035; P0.01; for each minute increase of donor extraction time). Besides donor extraction time, cold ischemia time, warm ischemia time, and donor risk index had a significant effect on early graft function.We demonstrate an independent effect of donor extraction time on graft function after liver transplantation. Efforts to minimize donor extraction time could improve early graft function in liver transplantation.
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- 2018
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30. State of the Science in Deceased Organ Donor Management
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Madhukar S. Patel, Claus U. Niemann, Mitchell B. Sally, and Darren J. Malinoski
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Transplantation ,Intervention trials ,medicine.medical_specialty ,Deceased donor ,Hepatology ,business.industry ,Immunology ,030230 surgery ,Intervention studies ,Delayed Graft Function ,03 medical and health sciences ,0302 clinical medicine ,Transplant surgery ,Nephrology ,medicine ,030211 gastroenterology & hepatology ,Surgery ,State of the science ,Intensive care medicine ,business ,Donor management - Abstract
Research in deceased organ donor management offers an opportunity to increase the quantity and quality of organs available for transplantation. This article aims to appraise the current literature with a focus on reviewing deceased donor intervention trials. Aggressive critical care management after determination of brain death resulting in meeting of a donor management goal bundle has consistently demonstrated an association with significantly more organs transplanted per donor as well as improved graft outcomes. Although there is a dearth of experience with randomized donor intervention studies, dopamine and targeted mild therapeutic hypothermia have been found to significantly reduce delayed graft function in kidney recipients. Progress in understanding the ethical, legal, regulatory, policy, and organizational elements of organ donor research has provided a mechanism that allows for the endorsement of potentially impactful donor management studies. Ongoing trials should incorporate methods to ensure safety to all organs donated from donors enrolled in interventional trials.
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- 2018
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31. Intraoperative Management of Liver Transplant Patients Without the Routine Use of Renal Replacement Therapy
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Claus U. Niemann, Andrea Olmos, Mehdi Tavakol, Babak J. Orandi, John Feiner, Garrett R. Roll, Linda L. Liu, Lyle Burdine, Shareef Syed, and Dieter Adelmann
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Male ,medicine.medical_specialty ,Hyperkalemia ,medicine.medical_treatment ,030230 surgery ,Liver transplantation ,urologic and male genital diseases ,End Stage Liver Disease ,03 medical and health sciences ,Liver disease ,0302 clinical medicine ,Renal Dialysis ,Risk Factors ,Humans ,Medicine ,Renal Insufficiency ,Renal replacement therapy ,Dialysis ,Retrospective Studies ,Transplantation ,Intraoperative Care ,business.industry ,Retrospective cohort study ,Perioperative ,Middle Aged ,medicine.disease ,Kidney Transplantation ,female genital diseases and pregnancy complications ,Liver Transplantation ,Surgery ,Treatment Outcome ,Female ,030211 gastroenterology & hepatology ,medicine.symptom ,Acidosis ,business - Abstract
Background Renal failure is common among patients undergoing liver transplantation. Liver allocation based on the model for end-stage liver disease score has increased the number of recipients who require perioperative renal replacement therapy (RRT). Although RRT can be continued intraoperatively, the risks and benefits of intraoperative RRT are not well defined. The aim of this study is to report the intraoperative management of patients with pretransplant renal failure at a transplant center with extremely infrequent utilization of intraoperative RRT. Materials and methods We performed a retrospective analysis of all adult patients undergoing orthotopic liver or simultaneous liver-kidney (SLK) transplantation between June 2009 and December 2015. Patients were divided into 2 groups based on their need for pretransplant RRT. Results A total of 785 patients underwent liver or SLK transplant during the study period. One hundred and seventy-four patients (22.2%) required preoperative dialysis. Only 2 patients required intraoperative RRT. There was no difference in the incidence of acidosis or hyperkalemia between patients who required preoperative dialysis and those who did not. Conclusions We describe the successful management of patients undergoing liver or SLK transplantation almost entirely without the need for intraoperative RRT.
- Published
- 2018
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32. Potentially inappropriate liver transplantation in the era of the 'sickest first' policy – A search for the upper limits
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Tanja Krones, Michael Linecker, Randolph H. Steadman, Robert D. Truog, Claus U. Niemann, Thomas Berg, Ronald W. Busuttil, Philipp Dutkowski, Pierre-Alain Clavien, Henrik Petrowsky, University of Zurich, and Petrowsky, Henrik
- Subjects
medicine.medical_specialty ,Tissue and Organ Procurement ,Waiting Lists ,Hypertension, Pulmonary ,medicine.medical_treatment ,610 Medicine & health ,030230 surgery ,Liver transplantation ,Severity of Illness Index ,End Stage Liver Disease ,03 medical and health sciences ,Liver disease ,0302 clinical medicine ,Quality of life (healthcare) ,Internal medicine ,medicine ,Humans ,Intensive care medicine ,10217 Clinic for Visceral and Transplantation Surgery ,Equity (economics) ,Hepatology ,business.industry ,Mortality rate ,Limiting ,Liver Failure, Acute ,medicine.disease ,Liver Transplantation ,Surgery ,Transplantation ,surgical procedures, operative ,2721 Hepatology ,030211 gastroenterology & hepatology ,business - Abstract
Liver transplantation has emerged as a highly efficient treatment for a variety of acute and chronic liver diseases. However, organ shortage is becoming an increasing problem globally, limiting the applicability of liver transplantation. In addition, potential recipients are becoming sicker, thereby increasing the risk of losing the graft during transplantation or in the initial postoperative period after liver transplantation (three months). This trend is challenging the model for end-stage liver disease allocation system, where the sickest candidates are prioritised and no delisting criteria are given. The weighting of the deontological demand for "equity", trying to save every patient, regardless of the overall utility; and "efficiency", rooted in utilitarianism, trying to save as many patients as possible and increase the overall quality of life of patients facing the same problem, has to be reconsidered. In this article we are aiming to overcome the widespread concept of futility in liver transplantation, providing a definition of potentially inappropriate liver transplantation and giving guidance on situations where it is best not to proceed with liver transplantation, to decrease the mortality rate in the first three months after transplantation. We propose "absolute" and "relative" conditions, where early post-transplant mortality is highly probable, which are not usually captured in risk scores predicting post-transplant survival. Withholding liver transplantation for listed patients in cases where liver transplant is not deemed clearly futile, but is potentially inappropriate, is a far-reaching decision. Until now, this decision had to be discussed extensively on an individual basis, applying explicit communication and conflict resolution processes, since the model for end-stage liver disease score and most international allocation systems do not include explicit delisting criteria to support a fair delisting process. More work is needed to better identify cases where transplantation is potentially inappropriate and to integrate and discuss these delisting criteria in allocation systems, following a societal debate on what we owe to all liver transplant candidates.
- Published
- 2018
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33. Transplant anesthesia and critical care: Current research and possible future developments
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Gianni Biancofiore and Claus U. Niemann
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Transplantation ,medicine.medical_specialty ,Critical Care ,business.industry ,MEDLINE ,Anesthesiology and Pain Medicine ,Anesthesiology ,Humans ,Medicine ,Anesthesia ,Current (fluid) ,business ,Intensive care medicine - Published
- 2020
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34. The role of deceased donor liver biopsy: An analysis of 5449 liver transplant recipients
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Mitchell B. Sally, Jahan Mohebali, Madhukar S. Patel, Tahnee Groat, Parsia A. Vagefi, Claus U. Niemann, Taylor M. Coe, and Darren Malinoski
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medicine.medical_specialty ,Tissue and Organ Procurement ,medicine.medical_treatment ,Biopsy ,030230 surgery ,Liver transplantation ,03 medical and health sciences ,0302 clinical medicine ,Internal medicine ,Living Donors ,Medicine ,Humans ,Donor management ,Transplantation ,Deceased donor ,medicine.diagnostic_test ,business.industry ,Graft Survival ,Patient survival ,Tissue Donors ,Transplant Recipients ,Liver Transplantation ,Liver ,Liver biopsy ,Hispanic ethnicity ,030211 gastroenterology & hepatology ,Graft survival ,business - Abstract
Background No standard exists for the use of deceased donor liver biopsy during procurement. We sought to evaluate liver biopsy and the impact of findings on outcomes and graft utilization. Methods A prospective observational study of donors after neurologic determination of death was conducted from 02/2012-08/2017 (16 OPOs). Donor data were collected through the UNOS Donor Management Goals Registry Web Portal and linked to the Scientific Registry of Transplant Recipients (SRTR) for recipient outcomes. Recipients of biopsied donor livers (BxDL) were studied and a Cox proportional hazard analysis was used to identify independent predictors of 1-year graft survival. Results Data from 5449 liver transplant recipients were analyzed, of which 1791(33%) received a BxDL. There was no difference in graft or patient survival between the non-BxDL and BxDL recipient groups. On adjusted analysis of BxDL recipients, macrosteatosis (21%-30%[n = 148] and >30%[n = 92]) was not found to predict 1-year graft survival, whereas increasing donor age (HR1.02), donor Hispanic ethnicity (HR1.62), donor INR (HR1.18), and recipient life support (HR2.29) were. Conclusions Excellent graft and patient survival can be achieved in recipients of BxDL grafts. Notably, as demonstrated by the lack of effect of macrosteatosis on survival, donor to recipient matching may contribute to these outcomes.
- Published
- 2019
35. Therapeutic Hypothermia in Organ Donors: Follow-up and Safety Analysis
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David A. Axelrod, Madhukar S. Patel, Tahnee Groat, Roger J. Lewis, Claus U. Niemann, Kristine Broglio, and Darren Malinoski
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Adult ,medicine.medical_specialty ,Brain Death ,Tissue and Organ Procurement ,Delayed Graft Function ,030230 surgery ,Kidney ,law.invention ,Body Temperature ,03 medical and health sciences ,0302 clinical medicine ,Randomized controlled trial ,law ,Hypothermia, Induced ,medicine ,Humans ,Kidney surgery ,Kidney transplantation ,Aged ,Proportional Hazards Models ,Transplantation ,business.industry ,Proportional hazards model ,Incidence (epidemiology) ,Graft Survival ,Hypothermia ,Middle Aged ,medicine.disease ,Kidney Transplantation ,Tissue Donors ,Surgery ,Perfusion ,surgical procedures, operative ,Treatment Outcome ,030211 gastroenterology & hepatology ,Patient Safety ,medicine.symptom ,business ,Follow-Up Studies - Abstract
In a recent trial, targeted mild hypothermia in brain-dead organ donors significantly reduced the incidence of delayed graft function after kidney transplantation. This trial was stopped early for efficacy. Here, we report long-term graft survival for all organs along with donor critical care end points.We assessed graft survival through 1 year of all solid organs transplanted from 370 donors who had been randomly assigned to hypothermia (34-35°C) or normothermia (36.5-37.5°C) before donation. Additionally, changes in standardized critical care end points were compared between donors in each group.Mild hypothermia was associated with a nonsignificant improvement in 1-year kidney transplant survival (95% versus 92%; hazard ratio, 0.61 [0.31-1.20]; P = 0.15). Mild hypothermia was associated with higher 1-year graft survival in the subgroup of standard criteria donors (97% versus 93%; hazard ratio, 0.39 [0.15 to -1.00]; P = 0.05). There were no significant differences in graft survival of extrarenal organs. There were no differences in critical care end points between groups.Mild hypothermia in the donor safely reduced the rate of delayed graft function in kidney transplant recipients without adversely affecting donor physiology or extrarenal graft survival. Kidneys from standard criteria donors who received targeted mild hypothermia had improved 1-year graft survival.
- Published
- 2019
36. Deceased organ donor factors influencing pancreatic graft transplantation and survival
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Michael P. Hutchens, Tahnee Groat, Claus U. Niemann, Elizabeth A. Swanson, Mitchell B. Sally, Margaret Katherine Ellis, Darren Malinoski, and Madhukar S. Patel
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Adult ,Male ,Organ procurement organization ,Brain Death ,medicine.medical_specialty ,Tissue and Organ Procurement ,medicine.medical_treatment ,030230 surgery ,Pancreas transplantation ,Article ,Donor Selection ,03 medical and health sciences ,0302 clinical medicine ,Diabetes mellitus ,medicine ,Humans ,Prospective Studies ,Intensive care medicine ,Transplantation ,Type 1 diabetes ,business.industry ,Insulin ,Middle Aged ,Prognosis ,medicine.disease ,Tissue Donors ,Survival Rate ,medicine.anatomical_structure ,Female ,030211 gastroenterology & hepatology ,Pancreas Transplantation ,Solid organ ,Pancreas ,business ,Follow-Up Studies - Abstract
Pancreatic transplantation has become a standard of care for complicated type 1 diabetes therapy. In the United States in 2015, there were approximately 1000 patients awaiting pancreas transplant, with the percentage of active listings at 65%, the highest in decades.1 Solid organ pancreata can be transplanted individually, after a kidney transplant (pancreas-after-kidney [PAK]), or with a simultaneous pancreas-kidney (SPK) transplant. As diabetes is cited as a major, in- creasing public health burden,2 pancreas transplant has been recommended by the American Diabetes Association and other national guidelines as an accepted treatment, particularly when coupled with end-stage renal disease.3 Benefits to pancreas transplantation, SPK, and PAK are well described, having both improvements in mortality when compared to those on the waiting list4 and better overall glycemic control, reducing number of hypoglycemic episodes compared to those on insulin regimens.5 In addition, pancreas transplantation has been shown to delay secondary complications of diabetes, such as cardiovascular disease6 and nervous system complications.7 Despite these demonstrated advantages for pancreatic transplantation, only approximately 10% of available organs are recovered from donors after brain death (DBD). Additionally, there has been an overall decline in pancreatic transplantation over the past decade.8 In pancreatic transplantation, inconsistent donor management and organ acceptance practices are pervasive. Potentially contributing to this lack of consistency in donor management is the fact that the current risk-adjustment models used to predict both organ procurement organization (OPO) donor pancreas utilization and transplant center graft survival models lack detailed donor critical care data. In an effort to increase standardization and data collection, several OPOs have collaborated to develop a checklist of critical care endpoints to guide the bedside care of potential organ donors. These endpoints are also known as donor management goals (DMGs), and they represent normal hemodynamic, respiratory, renal, acid-base, and endocrine parameters for an organ donor. Multiple studies have shown improvements in both organ utilization rates9–13 and recipient graft outcomes14–16 when these goals are met. The link between optimal management of the potential organ donor after brain death (DBD) and pancreatic graft utilization and function has not yet been explored in the literature, and we sought to further elucidate this relationship using a deceased organ donor database containing demographic and critical care data at 4 time points during donor management. Given anecdotal reports of insulin requirements being used as criteria for pancreatic acceptance or denial, we also sought to determine the relationship between insulin dose and pancreatic usage and function.
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- 2019
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37. Modeling the economic benefit of targeted mild hypothermia in deceased donor kidney transplantation
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Krista L. Lentine, Kristine Broglio, Claus U. Niemann, Mark A. Schnitzler, Madhukar S. Patel, Darren Malinoski, Tahnee Groat, Roger J. Lewis, and David A. Axelrod
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Male ,medicine.medical_specialty ,Mild hypothermia ,Brain Death ,Tissue and Organ Procurement ,Cold storage ,Delayed Graft Function ,Hypothermia ,medicine ,Humans ,Donor management ,health care economics and organizations ,Kidney transplantation ,Deceased donor kidney ,Transplantation ,business.industry ,Recovery of Function ,medicine.disease ,Prognosis ,Kidney Transplantation ,Tissue Donors ,Clinical trial ,Models, Economic ,Treatment Outcome ,Emergency medicine ,Female ,medicine.symptom ,Health Expenditures ,business ,Follow-Up Studies - Abstract
Delayed graft function (DGF) in kidney transplant significantly increases inpatient and outpatient cost. Targeted, mild hypothermia in organ donors after neurologic determination of death significantly reduced the rate of DGF in a recent randomized controlled clinical trial. To assess the potential economic benefit of national implementation of donor hypothermia, rates of reduction DGF were combined with estimates of the impact of DGF on hospital cost and total health expenditure for standard and extended criteria donor organs (SCD and ECD). DGF increases the cost of the transplant episode by $9487 for ECD transplant and $10 342 for SCD transplant. Medicare recipients with DGF incur an additional $18 513 spending for ECD and $14 948 in SCD transplants over the first year. An absolute reduction in DGF rate after kidney transplantation consistent with trial results (ECD 25%, SCD 7%) has the potential to lower annual hospital cost for kidney transplant by $13 178 746 and annual Medicare spending by $20 970 706 compared to standard donor management practice using static cold storage. Targeted mild hypothermia improves care of renal transplant patients by safely reducing DGF rates in both ECD and SCD transplant. Broader application of this safe, effective, and low-cost intervention could reduce healthcare expenditures for providers and insurers.
- Published
- 2019
38. Perioperative Care of Patients Undergoing Kidney Transplantation
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Claus U. Niemann, Kate Kronish, and Andrea Olmos
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medicine.medical_specialty ,business.industry ,Perioperative care ,medicine ,business ,medicine.disease ,Kidney transplantation ,Surgery - Published
- 2019
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39. Protecting the Kidney in Liver Transplant Recipients: Practicee-Based Recommendations From the American Society of Transplantation Liver and Intestine Community of Practice
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Jacqueline G. O'Leary, Pratima Sharma, Claus U. Niemann, Sumeet K. Asrani, Alexander C. Wiseman, Josh Levitsky, and John J. Fung
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Nephrology ,medicine.medical_specialty ,medicine.medical_treatment ,Population ,Renal function ,030230 surgery ,Liver transplantation ,03 medical and health sciences ,Liver disease ,0302 clinical medicine ,Internal medicine ,medicine ,Immunology and Allergy ,Pharmacology (medical) ,Intensive care medicine ,education ,Transplantation ,Kidney ,education.field_of_study ,business.industry ,medicine.disease ,medicine.anatomical_structure ,030211 gastroenterology & hepatology ,business ,Kidney disease - Abstract
Both acute and chronic kidney disease are common after liver transplantation and result in significant morbidity and mortality. The introduction of the Model for End-stage Liver Disease score has directly correlated with an increased prevalence of perioperative renal dysfunction and the number of simultaneous liver-kidney transplantations performed. Kidney dysfunction in this population is typically multifactorial and related to preexisting conditions, pretransplantation renal injury, perioperative events, and posttransplantation nephrotoxic immunosuppressive therapies. The management of kidney disease after liver transplantation is challenging, as by the time the serum creatinine level is significantly elevated, few interventions affect the course of progression. Also, immunological factors such as antibody-mediated kidney rejection have become of greater interest given the rising liver-kidney transplant population. Therefore, this review, assembled by experts in the field and endorsed by the American Society of Transplantation Liver and Intestine Community of Practice, provides a critical assessment of measures of renal function and interventions aimed at preserving renal function early and late after liver and simultaneous liver-kidney transplantation. Key points and practice-based recommendations for the prevention and management of kidney injury in this population are provided to offer guidance for clinicians and identify gaps in knowledge for future investigations.
- Published
- 2016
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40. Measurements of ion velocity distributions in a large scale laser-produced plasma
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P. V. Heuer, Carmen Constantin, Derek Schaeffer, Claus U. Niemann, and R. S. Dorst
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010302 applied physics ,Materials science ,Plasma ,Laser ,01 natural sciences ,010305 fluids & plasmas ,Ion ,Computational physics ,law.invention ,Signal-to-noise ratio ,Physics::Plasma Physics ,law ,Temporal resolution ,0103 physical sciences ,Millimeter ,Spectral resolution ,Instrumentation ,Monochromator - Abstract
Laser-produced plasma velocity distributions are an important, but difficult quantity to measure. We present a non-invasive technique for measuring individual charge state velocity distributions of laser-produced plasmas using a high temporal and spectral resolution monochromator. The novel application of this technique is its ability to detect particles up to 7 m from their inception (significantly larger than most laboratory plasma astrophysics experiments, which take place at or below the millimeter scale). The design and assembly of this diagnostic is discussed in terms of maximizing the signal to noise ratio, maximizing the spatial and temporal resolution, and other potential use cases. The analysis and results of this diagnostic are demonstrated by directly measuring the time-of-flight velocity of all ion charge states in a laser produced carbon plasma.
- Published
- 2020
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41. Impact of Deceased Donor Management on Donor Lung Use and Recipient Graft Survival
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Elizabeth A. Swanson, Madhukar S. Patel, Michael Hutchens, Claus U. Niemann, Tahnee Groat, Darren J. Malinoski, and Mitchell B. Sally
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Surgery - Published
- 2020
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42. Impact of Deceased Donor Management on Donor Heart Use and Recipient Graft Survival
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Tahnee Groat, Elizabeth A. Swanson, Claus U. Niemann, Kiran K. Khush, Michael P. Hutchens, Tony Adams, Mitchell B. Sally, Madhukar S. Patel, Darren J. Malinoski, and Salvador De La Cruz
- Subjects
Adult ,Male ,Organ procurement organization ,Brain Death ,medicine.medical_specialty ,Tissue and Organ Procurement ,Expanded Criteria Donor ,Article ,03 medical and health sciences ,chemistry.chemical_compound ,0302 clinical medicine ,Internal medicine ,Fraction of inspired oxygen ,medicine ,Humans ,Prospective Studies ,Aged ,Creatinine ,Ejection fraction ,business.industry ,Graft Survival ,Thyroid ,Odds ratio ,Middle Aged ,medicine.anatomical_structure ,chemistry ,030220 oncology & carcinogenesis ,Cardiology ,Heart Transplantation ,Female ,030211 gastroenterology & hepatology ,Surgery ,business ,Hormone - Abstract
BACKGROUND: Current risk-adjusted models used to predict donor heart utilization and cardiac graft survival from organ donors after brain death (DBDs) do not include bedside critical care data. We sought to identify novel independent predictors of heart utilization and graft survival to better understand the relationship between donor management and transplant outcomes. STUDY DESIGN: Prospective observational study of DBDs managed from 2008 to 2013 by 10 organ procurement organizations. Demographic data, critical care parameters, and treatments were recorded at three standardized time points during donor management. The primary outcome measures were donor heart utilization and cardiac graft survival. RESULTS: From 3,433 DBDs, 1,134 (33%) hearts were transplanted and 969 (85%) cardiac grafts survived after 684 (± 392) days of follow-up. After multivariable analysis, independent positive predictors of heart utilization included standard criteria donor status (OR = 3.93), male sex (OR = 1.68), ejection fraction > 50% (OR = 1.64), and PaO(2):FiO(2) > 300 (OR = 1.31). Independent negative predictors of heart utilization included donor age (OR = 0.94), body mass index > 30 kg/m(2) (OR = 0.78), serum creatinine (OR = 0.83), and use of thyroid hormone (OR = 0.78). As for graft survival, after controlling for known recipient risk factors, thyroid hormone dose was the only independent predictor (OR = 1.04 per μg/hr). CONCLUSION: Modifiable critical care parameters and treatments predict donor heart utilization and cardiac graft survival. The discordant relationship between thyroid hormone and donor heart utilization (negative predictor) versus cardiac graft survival (positive predictor) warrants further investigation.
- Published
- 2020
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43. Bacchus Listed for a Liver Transplant: Comment
- Author
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Claus U. Niemann
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medicine.medical_specialty ,Anesthesiology and Pain Medicine ,business.industry ,General surgery ,medicine ,MEDLINE ,business - Published
- 2020
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44. The Continued Need for Clinical Trials in Deceased Organ Donor Management
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Claus U. Niemann, Lorraine B. Ware, and Michael A. Matthay
- Subjects
Transplantation ,medicine.medical_specialty ,Brain Death ,Tissue and Organ Procurement ,business.industry ,Naloxone ,MEDLINE ,030230 surgery ,Hypoxia (medical) ,Tissue Donors ,Clinical trial ,03 medical and health sciences ,0302 clinical medicine ,Text mining ,Medicine ,Humans ,030211 gastroenterology & hepatology ,medicine.symptom ,business ,Intensive care medicine ,Hypoxia ,Donor management - Published
- 2018
45. Organ Donor Management: Part 1. Toward a Consensus to Guide Anesthesia Services During Donation After Brain Death
- Author
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Marina Moguilevitch, Anil Paramesh, Nikole A. Neidlinger, Claus U. Niemann, Elling E. Eidbo, Ernesto A. Pretto, Daniel J. Lebovitz, Michael J. Souter, James Y. Findlay, Pamela R. Roberts, and Gerhard Wagener
- Subjects
medicine.medical_specialty ,Brain Death ,Consensus ,Tissue and Organ Procurement ,Critical Care ,business.industry ,Resuscitation ,030230 surgery ,Organ transplantation ,Tissue Donors ,Donation after brain death ,03 medical and health sciences ,Organ procurement ,0302 clinical medicine ,Anesthesiology and Pain Medicine ,030202 anesthesiology ,Perioperative care ,medicine ,Fluid Therapy ,Humans ,Anesthesia ,Cardiology and Cardiovascular Medicine ,Intensive care medicine ,business ,Donor management - Abstract
Worldwide 715 482 patients have received a lifesaving organ transplant since 1988. During this time, there have been advances in donor management and in the perioperative care of the organ transplant recipient, resulting in marked improvements in long-term survival. Although the number of organs recovered has increased year after year, a greater demand has produced a critical organ shortage. The majority of organs are from deceased donors; however, some are not suitable for transplantation. Some of this loss is due to management of the donor. Improved donor care may increase the number of available organs and help close the existing gap in supply and demand. In order to address this concern, The Organ Donation and Transplantation Alliance, the Association of Organ Procurement Organizations, and the Transplant and Critical Care Committees of the American Society of Anesthesiologists have formulated evidence-based guidelines, which include a call for greater involvement and oversight by anesthesiologists and critical care specialists, as well as uniform reporting of data during organ procurement and recovery.
- Published
- 2017
46. Comments on 'Impact of spontaneous donor hypothermia on graft outcomes after kidney transplantation'
- Author
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Claus U. Niemann, Kristine Broglio, and Darren Malinoski
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Mild hypothermia ,medicine.medical_specialty ,Tissue and Organ Procurement ,Transplants ,Economic shortage ,Hypothermia ,030230 surgery ,03 medical and health sciences ,0302 clinical medicine ,Allograft survival ,medicine ,Immunology and Allergy ,Humans ,Pharmacology (medical) ,Kidney transplantation ,Transplantation ,business.industry ,Retrospective cohort study ,medicine.disease ,Kidney Transplantation ,Tissue Donors ,Surgery ,Intervention research ,030211 gastroenterology & hepatology ,medicine.symptom ,business - Abstract
Using a retrospective cohort that was part of a donor intervention trial published in 2009 1, Schnuelle et al report in this issue that spontaneous hypothermia in deceased organ donors resulted in decreased recipient renal delayed graft function2. Allograft survival was not statistically significantly different during long-term follow up. While spontaneous hypothermia is likely a distinct physiologic process compared to targeted mild hypothermia, as in our previously reported randomized controlled trial3, the findings of the current retrospective study further confirm our impression that therapeutic mild hypothermia and deceased organ donor intervention research, in general, hold tremendous potential for addressing the ongoing shortage of organs available for transplantation. This article is protected by copyright. All rights reserved.
- Published
- 2017
47. Expedited Evaluation for Liver Transplantation
- Author
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Mehdi Tavakol, Hillary J. Braun, Claus U. Niemann, Anna Mello, Dieter Adelmann, and Nancy L. Ascher
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Transplantation ,medicine.medical_specialty ,business.industry ,medicine.medical_treatment ,Medicine ,Patient Acuity ,Liver transplantation ,business ,Surgery - Published
- 2018
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48. Functional elements associated with hepatic regeneration in living donors after right hepatic lobectomy
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Brenda W. Gillespie, Gregory T. Everson, John C. Hoefs, Norah Milne, Nathan P. Goodrich, James E. Everhart, Andrea Herman, Kim M. Olthoff, Shannon Lauriski, Robert E. Dupuis, and Claus U. Niemann
- Subjects
Transplantation ,medicine.medical_specialty ,Hepatology ,biology ,business.industry ,Bilirubin ,medicine.medical_treatment ,Liter ,Blood flow ,Liver transplantation ,Gastroenterology ,Liver regeneration ,Surgery ,chemistry.chemical_compound ,Alanine transaminase ,chemistry ,Internal medicine ,medicine ,biology.protein ,Hepatectomy ,business ,Prospective cohort study - Abstract
We quantified the rates of hepatic regeneration and functional recovery for 6 months after right hepatic lobectomy in living donors for liver transplantation. Twelve donors were studied pre-donation (baseline); 8 were retested at a mean ± SD of 11±3 days after donation (T1), 10 were retested at a mean of 91±9 days after donation (T2), and 10 were retested at a mean of 185±17 days after donation (T3). Liver and spleen volumes were measured with computed tomography (CT) and single-photon emission computed tomography (SPECT). Hepatic metabolism was assessed with caffeine and erythromycin, and hepatic blood flow (HBF) was assessed with cholates, galactose, and the perfused hepatic mass (PHM) by SPECT. The regeneration rates (mL kg(-1) of body weight day(-1)) by CT were 0.60±0.22 mL from the baseline to T1, 0.05±0.02 mL from T1 to T2, and 0.01±0.01 from T2 to T3; by SPECT they were 0.54±0.20, 0.04±0.01, and 0.01±0.02, respectively. At T3, the liver volumes were 84%±7% of the baseline according to CT and 92%±13% of the baseline according to SPECT. Changes in the hepatic metabolism did not achieve statistical significance. At T1, the unadjusted clearance ratios with respect to the baseline were 0.75±0.07 for intravenous cholate (P
- Published
- 2013
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49. Infrared pupillometry to detect the light reflex during cardiopulmonary resuscitation: A case series
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Claus U. Niemann, Merlin D. Larson, and Matthias Behrends
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Adult ,Male ,Resuscitation ,Light ,Infrared Rays ,medicine.medical_treatment ,Emergency Nursing ,Reflex, Pupillary ,Young Adult ,Predictive Value of Tests ,Humans ,Medicine ,Pupillary light reflex ,Cardiopulmonary resuscitation ,Aged ,Aged, 80 and over ,business.industry ,Neurological status ,Light reflex ,Middle Aged ,Cardiopulmonary Resuscitation ,Predictive value of tests ,Anesthesia ,Emergency Medicine ,Reflex ,Female ,Cardiology and Cardiovascular Medicine ,business ,Pupillometry - Abstract
Background The presence or absence of the pupillary light reflex following cardiopulmonary resuscitation has been shown to have prognostic value. We asked whether the light reflex could be objectively measured during cardiopulmonary resuscitation in humans and whether the quality of the reflex was associated with outcome. Methods Sixty-seven in-hospital code blue alerts were attended of which 30 met our inclusion criteria. Portable infrared pupillometry was used to measure the light reflex during each code. The reliability of the presence of the light reflex during each code as a predictor of survival and neurological outcome was analyzed statistically using the Barnard's Exact test. Results In 25 patients (83%) the pupillary light reflex was detectable throughout or during a part of the resuscitation. Continuous presence of the light reflex or absence for less than 5 min during resuscitation was associated with early survival of the code and a good neurological outcome. In contrast, no patients without a light reflex or with a gradually deteriorating light reflex survived the code and absence of a pupillary light reflex for more than 5 min was associated with an unfavorable outcome. Conclusion Portable infrared pupillary measurements can reliably demonstrate the presence and quality of the pupillary light reflex after cardiac arrest and during resuscitation. In our limited case series, the presence of the pupillary light reflexes obtained in serial measurements during resuscitation was associated with early survival and a favorable neurological status in the recovery period.
- Published
- 2012
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50. Optimizing cost-effectiveness in perioperative care for liver transplantation: A model for low- to medium-income countries
- Author
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John R. Klinck, Karina Rando, Pilar Taura, and Claus U. Niemann
- Subjects
Transplantation ,medicine.medical_specialty ,Modality (human–computer interaction) ,Modalities ,Hepatology ,Cost–benefit analysis ,Cost effectiveness ,business.industry ,medicine.medical_treatment ,Staffing ,Liver transplantation ,medicine ,Surgery ,Intensive care medicine ,business ,Adverse effect ,Tranexamic acid ,medicine.drug - Abstract
Although liver transplantation (LT) is a highly effective treatment, it has been considered too costly for publicly funded health systems in many countries with low to medium average incomes. However, with economic growth and improving results, some governments are reconsidering this position. Cost-effectiveness data for LT are limited, especially in perioperative care, and the techniques and costs vary widely between centers without overt differences in outcomes. Anesthesiologists working in new programs find it difficult to determine which modalities are essential, which are needed only in exceptional circumstances, and which may be omitted without effects on outcomes. We investigated key elements of preoperative evaluations, intraoperative management, and early postoperative care that might significantly affect costs in order to develop a best-value approach for new programs in resource-limited health systems. We identified all modalities of care commonly used in anesthesia and perioperative care for adult LT along with their costs. Those considered to be universally accepted as minimum requirements for safe care were excluded from the analysis, and so were those considered to be safe and low-cost, even when evidence of efficacy was lacking. The remaining items were, therefore, those with uncertain or context-restricted value and significant costs. A systematic review of the published evidence, practice surveys, and institutional guidelines was performed, and the evidence was graded and summarized. With respect to costs and benefits, each modality was then cited as strongly recommended, recommended or optional, or no recommendation was made because of insufficient evidence. Sixteen modalities, which included preoperative cardiovascular imaging, venovenous bypass, pulmonary artery catheterization, high-flow fluid warming devices, drug therapies for hemostasis, albumin, cell salvage, anesthetic drugs, personnel (staffing) requirements, and early extubation, were assessed. Only high-flow fluid warming was strongly recommended. The recommended modalities included preoperative echocardiography, cell salvage, tranexamic acid and early extubation. Six others were rated optional, and there was insufficient evidence for 5 modalities. We conclude that some costly techniques and treatments can be omitted without adverse effects on outcomes. Liver Transpl 17:1247–1278, 2011. © 2011 AASLD.
- Published
- 2011
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