Article
Hematology
Gloria F. Gerber, Robert A. Brodsky
Summary: This article discusses the theoretical basis and clinical studies of using C3 inhibitors in the treatment of PNH, as well as provides suggestions for treatment sequencing.
Article
Medicine, General & Internal
Peter Hillmen, Jeff Szer, Ilene Weitz, Alexander Roeth, Britta Hoechsmann, Jens Panse, Kensuke Usuki, Morag Griffin, Jean-Jacques Kiladjian, Carlos de Castro, Hisakazu Nishimori, Lisa Tan, Mohamed Hamdani, Pascal Deschatelets, Cedric Francois, Federico Grossi, Temitayo Ajayi, Antonio Risitano, Regis Peffault de la Tour
Summary: The study demonstrated that Pegcetacoplan was superior to eculizumab in improving hemoglobin and clinical and hematologic outcomes in patients with PNH by providing broad hemolysis control, including control of intravascular and extravascular hemolysis.
NEW ENGLAND JOURNAL OF MEDICINE
(2021)
Review
Medicine, General & Internal
Bruno Fattizzo, Fabio Serpenti, Juri Alessandro Giannotta, Wilma Barcellini
Summary: Paroxysmal nocturnal hemoglobinuria (PNH) is an intriguing disease with ongoing research on its pathophysiology, diagnostics, and treatment. Advanced flow cytometry techniques have enabled detection of small PNH clones, but data interpretation remains challenging. New complement inhibitors may improve patients' quality of life and response rates, but questions regarding their use and long-term safety need further investigation.
JOURNAL OF CLINICAL MEDICINE
(2021)
Review
Hematology
Austin G. Kulasekararaj, Ioanna Lazana
Summary: Paroxysmal nocturnal hemoglobinuria (PNH) is a rare hematological disorder characterized by deficiency of GPI-linked complement regulators. Despite the introduction of C5 inhibitors, residual hemolysis still occurs, leading to anemia and transfusion dependency in some patients. The development of longer-acting and subcutaneous formulations of C5 inhibitors, as well as proximal complement inhibitors, have shown promising results in improving hemoglobin levels and reducing hemolysis. Combination treatments have also been explored. This review discusses the current therapeutic options and emerging approaches for PNH.
AMERICAN JOURNAL OF HEMATOLOGY
(2023)
Review
Immunology
Nicole Galli, Loredana Pettine, Mauro Panigada, Laura Daprai, Grazia Suriano, Anna Grancini, Wilma Barcellini, Bruno Fattizzo
Summary: This case report highlights the risk of life-threatening infection by non-groupable Neisseria meningitidis in a young patient with paroxysmal nocturnal haemoglobinuria (PNH) treated with ravulizumab. Prompt diagnosis and treatment are crucial in managing such infections in PNH patients on complement inhibitors.
FRONTIERS IN IMMUNOLOGY
(2023)
Review
Hematology
Jens Panse
Summary: In the past 20 years, therapy for paroxysmal nocturnal hemoglobinuria (PNH) mainly relied on antibody-based terminal complement inhibition. PNH is a disease characterized by a mutation that causes the absence or deficiency of complement-regulatory proteins on blood cells, leading to intravascular hemolysis and related complications. Recently, there has been a development of new drugs targeting the proximal and terminal complement cascade, with the approval of the first proximal complement inhibitor targeting C3 in 2021. This article aims to provide an overview of the progress made in PNH treatment and discuss the approved therapeutic options, as well as the potential impact and consequences of current and future treatments on patients' lives.
AMERICAN JOURNAL OF HEMATOLOGY
(2023)
Article
Hematology
Austin G. Kulasekararaj, Antonio M. Risitano, Jaroslaw P. Maciejewski, Rosario Notaro, Peter Browett, Jong Wook Lee, Mingjun Huang, Michael Geffner, Robert A. Brodsky
Summary: The study showed that adding an oral complement inhibitor danicopan to PNH patients who were dependent on eculizumab led to an increase in Hgb levels, a reduction in blood transfusion requirements, and improvements in fatigue, with good tolerability.
Article
Multidisciplinary Sciences
Patricia Eiko Yamakawa, Ana Rita Fonseca, Ismael Dale Cotrim Guerreiro da Silva, Matheus Vescovi Goncalves, Dirce Maria Marchioni, Antonio Augusto Ferreira Carioca, David Michonneau, Celso Arrais-Rodrigues
Summary: This study aimed to identify the dysfunctional pathways involved in the pathophysiology of PNH by comparing the metabolic profiles of PNH patients to healthy controls, as well as analyzing the metabolomic profiles before and after eculizumab treatment. The results showed significant differences in metabolomes between PNH patients and healthy controls, and eculizumab treatment appeared to improve defects in the Acyl CoA metabolism, reducing oxidative stress and inflammation.
Review
Hematology
Austin G. Kulasekararaj, Robert A. Brodsky, Jun-ichi Nishimura, Christopher J. Patriquin, Hubert Schrezenmeier
Summary: Paroxysmal nocturnal hemoglobinuria (PNH) is a rare blood disorder that can cause hemolysis, thrombosis, and organ damage. LDH is used as a biomarker for diagnosis. Eculizumab and ravulizumab, inhibitors of the terminal complement component 5 (C5), have shown effectiveness in treating PNH.
THERAPEUTIC ADVANCES IN HEMATOLOGY
(2022)
Review
Immunology
Melissa A. Colden, Sushant Kumar, Bolormaa Munkhbileg, Daria V. Babushok
Summary: Paroxysmal Nocturnal Hemoglobinuria (PNH) is a disease that involves mutations in a specific gene, leading to hemolysis and abnormal clonal expansion of blood cells. The mechanisms behind this expansion are still debated, but recent advancements in research and technology offer new opportunities for understanding the disease.
FRONTIERS IN IMMUNOLOGY
(2022)
Article
Hematology
Raymond Siu Ming Wong, Juan Ramon Navarro-Cabrera, Narcisa Sonia Comia, Yeow Tee Goh, Henry Idrobo, Daolada Kongkabpan, David Gomez-Almaguer, Mohammed Al-Adhami, Temitayo Ajayi, Paulo Alvarenga, Jessica Savage, Pascal Deschatelets, Cedric Francois, Federico Grossi, Teresita Dumagay
Summary: PNH is a rare disease characterized by complement-mediated hemolysis. Pegcetacoplan, the first C3-targeted therapy, has shown superior efficacy and safety compared to supportive care in complement inhibitor-naive patients with PNH, leading to significant stabilization of hemoglobin levels and reduction in lactate dehydrogenase levels.
Article
Pharmacology & Pharmacy
Jun-ichi Nishimura, Antoine Soubret, Noriko Arase, Simon Buatois, Masaki Hotta, Jean-Eric Charoin, Yoshikazu Ito, Sasha Sreckovic, Hiroyuki Takamori, Christoph Bucher, Yasutaka Ueda, Jules Hernandez-Sanchez, Keisuke Gotanda, Gregor Jordan, Kenji Shinomiya, Julia Ramos, Jin Seok Kim, Jens Panse, Regis Peffault de Latour, Alexander Roeth, Eiichi Morii, Hubert Schrezenmeier, Yoshitaka Isaka, Simona Sica, Yuzuru Kanakura, Sung-Soo Yoon, Taroh Kinoshita, Ido Paz-Priel, Alexandre Sostelly
Summary: Drug-target-drug complexes (DTDCs) are newly observed phenomena in patients switching from eculizumab to crovalimab. Optimizing crovalimab dosing reduces the proportion of large DTDCs, ensures adequate complement inhibition, and may improve safety.
CLINICAL PHARMACOLOGY & THERAPEUTICS
(2023)
Article
Pharmacology & Pharmacy
Sung-Eun Lee, Jong Wook Lee
Summary: This article reviews the safety data of eculizumab and ravulizumab in the treatment of PNH, especially in special settings. Expert opinion suggests that both drugs have been found to be safe and well tolerated in clinical trials, but vigilance towards meningococcal infections is still necessary.
EXPERT OPINION ON DRUG SAFETY
(2021)
Article
Hematology
Deniz Goren Sahin, Olga Meltem Akay, Muzaffer Keklik, Vahap Okan, Abdullah Karakus, Cengiz Demir, Mehmet Ali Erkurt, Kadir Ilkkilic, Rahsan Yildirim, Gulsum Akgun Cagliyan, Salih Aksu, Mehmet Hilmi Dogu, Mehmet Sinan Dal, Volkan Karakus, Ali Ihsan Gemici, Hatice Terzi, Engin Kelkitli, Serdar Sivgin, Ali Unal, Mehmet Yilmaz, Orhan Ayyildiz, Serdal Korkmaz, Bulent Eser, Fevzi Altuntas
Summary: This study aimed to collect PNH patient data from hematology centers across Turkey to identify clinical features and management. After evaluating patients from 19 different institutions, it was found that fatigue and abdominal pain were the most frequent presenting symptoms. This study provided valuable information for understanding the disease and differences between patients in Turkey and existing literature.
ANNALS OF HEMATOLOGY
(2021)
Review
Hematology
Robert A. Brodsky
Summary: Paroxysmal nocturnal hemoglobinuria (PNH) is a rare complement-mediated hemolytic anemia with diverse manifestations, requiring differentiated treatment approaches; terminal complement inhibition is effective for intravascular hemolysis treatment but not bone marrow failure; novel complement inhibitors under clinical development show promising prospects for future applications.
Article
Urology & Nephrology
Deirdre Sawinski, Hanna Lindner, Robert Fitzsimmons, Justine Shults, Jayme E. Locke, Jordana B. Cohen, Paul A. MacLennan, Peter P. Reese
Summary: This study examined the association between nonadherent behaviors related to dialysis treatment and posttransplant outcomes, finding that certain nonadherence metrics were associated with allograft loss and patient mortality. Behavioral metrics were more closely associated with outcomes, highlighting the importance of considering the implications of nonadherent behaviors before excluding patients from transplantation.
AMERICAN JOURNAL OF KIDNEY DISEASES
(2022)
Article
Surgery
Kai He, Saulat S. Sheikh, Babak J. Orandi, Blair Smith, Jayme E. Locke, Robert M. Cannon
Summary: This study analyzed the outcomes of third time liver transplantation in the US using the UNOS dataset. The results showed that the survival rate of third time liver transplant recipients was significantly lower compared to primary liver transplant and retransplant. However, appropriate patient selection can result in acceptable survival outcomes.
AMERICAN JOURNAL OF SURGERY
(2022)
Article
Surgery
Christine M. Durand, Sander Florman, Jennifer D. Motter, Diane Brown, Darin Ostrander, Sile Yu, Tao Liang, William A. Werbel, Andrew Cameron, Shane Ottmann, James P. Hamilton, Andrew D. Redd, Mary G. Bowring, Yolanda Eby, Reinaldo E. Fernandez, Brianna Doby, Nazzarena Labo, Denise Whitby, Wendell Miley, Rachel Friedman-Moraco, Nicole Turgeon, Jennifer C. Price, Peter Chin-Hong, Peter Stock, Valentina Stosor, Varvara A. Kirchner, Timothy Pruett, David Wojciechowski, Nahel Elias, Cameron Wolfe, Thomas C. Quinn, Jonah Odim, Megan Morsheimer, Sapna A. Mehta, Meenakshi M. Rana, Shirish Huprikar, Allan Massie, Aaron A. R. Tobian, Dorry L. Segev
Summary: In this multicenter pilot study of HIV D+/R+ LT, patient and graft survival were better than historical cohorts, however, a potential increase in infections and cancer merits further investigation.
AMERICAN JOURNAL OF TRANSPLANTATION
(2022)
Article
Pediatrics
Joshua W. Purvis, Babak J. Orandi, Deepti Dhall, Chandler McLeod, Luz Helena Gutierrez Sanchez, Meagan Gray, Kayla Frey, Saulat S. Sheikh, Robert M. Cannon, Norah A. Terrault, Cora E. Lewis, Jayme E. Locke
Summary: The study found that the proportion of pediatric obese donors with hepatic macrosteatosis increased over time, but pediatric macrosteatosis did not appear to adversely affect recipient outcomes.
PEDIATRIC TRANSPLANTATION
(2022)
Article
Immunology
Michelle Kim, Jeffrey Stern, Ryan Robalino, Elaina P. Weldon, NicoleM Ali, Sapna A. Mehta, Zoe A. Stewart, Bonnie E. Lonze
Summary: Direct-acting antiviral (DAA) therapeutics have made it increasingly common to transplant organs from donors infected with hepatitis C virus (HCV+) into recipients without (HCV-). This study retrospectively reviewed cases in which recipients' family members reported needlestick exposures at home following discharge of the transplant recipient from the hospital. The analysis found that caregiver needlestick exposures occurred in 1.64% of HCV+ into HCV- transplants at our center, with the exposed individuals aiding in diabetic management and the exposure occurring via lancets or insulin needles. Further surveillance and treatment protocols are needed for centers performing these transplants to address potential secondary risks to family members and caregivers.
TRANSPLANT INFECTIOUS DISEASE
(2022)
Editorial Material
Surgery
Saulat S. Sheikh, Margaret M. Romine, Jayme E. Locke
AMERICAN JOURNAL OF SURGERY
(2022)
Article
Surgery
Robert M. Cannon, Ariann F. Nassel, Jeffery T. Walker, Saulat S. Sheikh, Babak J. Orandi, Raymond J. Lynch, Malay B. Shah, David S. Goldberg, Jayme E. Locke
Summary: This study found that blood types AB and B were more frequent in non-recovered DCD livers compared to actual donors. The driving time between the donor hospital and transplant center and the percentage located within a transplant hospital showed no significant difference between non-recovered DCD livers and actual donors. The donation service area (DSA) of a donor hospital had a significant impact on the recovery of DCD livers.
AMERICAN JOURNAL OF SURGERY
(2022)
Editorial Material
Surgery
Vijay Subramanian, Christopher Anderson, Seth Karp, Stephen Pastan, David Gerber, Jayme Locke, Ari Cohen, Malay Shah, Vincent Casingal, Robert Strata, Neeraj Singh, Derek DuBay, Kiran Dhanireddy
Summary: During the early wave of the COVID-19 pandemic, the Scientific Registry of Transplant Recipients (SRTR) implemented a blackout period for transplant outcomes reporting, which may introduce bias in favor of certain regions and harm others due to variations in the effects of COVID-19 infections.
AMERICAN JOURNAL OF TRANSPLANTATION
(2022)
Article
Surgery
Syed Sikandar Raza, Gaurav Agarwal, Douglas Anderson, Mark Deierhoi, Huma Fatima, Michael Hanaway, Jayme Locke, Paul MacLennan, Babak Orandi, Carlton Young, Roslyn B. Mannon, Michael E. Seifert
Summary: The study suggests that conducting time-zero biopsies post kidney transplantation can detect donor organ abnormalities, which can independently predict composite endpoints such as acute rejection, graft failure, and death. Particularly for deceased donor kidney transplant patients with high KDPI scores, abnormal time-zero histology is strongly associated with worse outcomes.
CLINICAL TRANSPLANTATION
(2022)
Article
Medicine, General & Internal
Robert A. Montgomery, Jeffrey M. Stern, Bonnie E. Lonze, Vasishta S. Tatapudi, Massimo Mangiola, Ming Wu, Elaina Weldon, Nikki Lawson, Cecilia Deterville, Rebecca A. Dieter, Brigitte Sullivan, Gabriella Boulton, Brendan Parent, Greta Piper, Philip Sommer, Samantha Cawthon, Erin Duggan, David Ayares, Amy Dandro, Ana Fazio-Kroll, Maria Kokkinaki, Lars Burdorf, Marc Lorber, Jef D. Boeke, Harvey Pass, Brendan Keating, Adam Griesemer, Nicole M. Ali, Sapna A. Mehta, Zoe A. Stewart
Summary: This study demonstrates that genetically modified pig kidney xenografts remained viable and functioned effectively in brain-dead human recipients for 54 hours, without signs of hyperacute rejection. This could potentially be a significant solution to the shortage of human organs for transplantation.
NEW ENGLAND JOURNAL OF MEDICINE
(2022)
Review
Urology & Nephrology
Christophe Hansen-Estruch, Paige M. Porrett, Vineeta Kumar, Jayme E. Locke
Summary: This review provides an update on recent advances in kidney xenotransplantation, with a focus on the proximity of clinical trials in humans. The studies have shown that genetic engineering of pig kidneys has reduced their immunogenicity, making xenotransplantation feasible in nonhuman primates for months. Moreover, a recent study in a human model demonstrated that key findings from primate experiments can be generalized to humans. These advancements have overcome critical physiological, immunological, and technical barriers to the implementation of clinical trials in humans.
CURRENT OPINION IN NEPHROLOGY AND HYPERTENSION
(2022)
Article
Surgery
A. Cozette Killian, Alexis J. Carter, Rhiannon D. Reed, Brittany A. Shelton, Haiyan Qu, Chandler McLeod, Babak J. Orandi, Robert M. Cannon, Douglas Anderson, Paul A. MacLennan, Vineeta Kumar, Michael Hanaway, Jayme E. Locke
Summary: Community-level vulnerability is associated with poor fidelity in the Living Donor Navigator Program, and factors such as community unemployment rate, single-parent households, minority population, and households without vehicles are associated with increased risk of self-advocacy.
Article
Surgery
Bofeng Chen, Ashley V. Alford, Bonnie E. Lonze, Lee C. Zhao
Summary: Single-port robotic-assisted laparoscopic surgery is a promising approach for the treatment of ureteral strictures in renal transplantation patients. The use of concurrent ureteroscopy and near-infrared fluorescence enables safe and rapid identification of the ureter, and side-to-side anastomosis allows for preservation of ureteral vasculature.
AMERICAN JOURNAL OF TRANSPLANTATION
(2023)
Article
Surgery
John T. Killian, Julie A. Houp, Greer A. Burkholder, Salomon A. Roman Soto, A. Cozette Killian, Song C. Ong, Nathaniel B. Erdmann, Paul A. Goepfert, Vera Hauptfeld-Dolejsek, Sixto M. Leal, Esther Zumaquero, Anoma Nellore, Gaurav Agarwal, Clifton E. Kew, Babak J. Orandi, Jayme E. Locke, Paige M. Porrett, Emily B. Levitan, Vineeta Kumar, Frances E. Lund
Summary: The study found that hospitalized SARS-CoV-2-infected kidney transplant patients are at risk for developing new donor-specific antibodies or increased levels of pre-existing antibodies, which are associated with late allograft dysfunction. COVID-19 vaccination and remdesivir administration may help reduce the risk of developing new or increased antibody responses.
TRANSPLANT INTERNATIONAL
(2022)