Review
Medicine, General & Internal
Senthil Sukumar, Bernhard Lammle, Spero R. Cataland
Summary: TTP is a rare but dangerous disorder characterized by hemolysis, thrombocytopenia, and ischemic damage, often caused by ADAMTS13 deficiency. Front-line treatment typically involves plasma exchange and immunosuppression, as well as drugs like rituximab and caplacizumab. Refractory cases may require alternative therapies.
JOURNAL OF CLINICAL MEDICINE
(2021)
Article
Hematology
Adrien Picod, Agnes Veyradier, Paul Coppo
Summary: iTTP is a rare and life-threatening disease currently treated with TPE and immunosuppression, while caplacizumab, a new treatment, shows faster platelet count recovery, decreased adverse outcomes, and reduced burden of care by inhibiting platelet aggregation and microthrombi formation.
JOURNAL OF THROMBOSIS AND HAEMOSTASIS
(2021)
Article
Medicine, General & Internal
Eleni Gavriilaki, Emmanuel Nikolousis, Eudoxia-Evaggelia Koravou, Sotiria Dimou-Besikli, Charalampos Kartsios, Anna Papakonstantinou, Anastasia Mpanti, Charalampos Pontikoglou, Christina Kalpadaki, Aikaterini Bitsani, Ilianna Tassi, Tasoula Touloumenidou, Thomas Chatziconstantinou, Maria Papathanasiou, Antonia Syrigou, Eleutheria Ztriva, Georgia Kaiafa, Evdokia Mandala, Zois Mellios, Dimitrios Karakasis, Alexandra Kourakli, Argiris Symeonidis, Eleni Kapsali, Helen H. Papadaki, Chrysavgi Lalayanni, Ioanna Sakellari
Summary: A multicenter real-world study was conducted to assess the safety and efficacy of caplacizumab in treating immune thrombotic thrombocytopenic pupura (iTTP). The results showed that caplacizumab is safe and effective in treating iTTP, including cases refractory to plasma exchange. Discontinuation of dosing guided by ADAMTS13 activity can lower the relapse rate.
FRONTIERS IN MEDICINE
(2023)
Editorial Material
Hematology
Paul Coppo, Berangere S. Joly
Summary: Therapeutic options for iTTP during pregnancy are limited, but caplacizumab may be a reasonable option when standard therapies are not effective, according to Odetola et al.
BRITISH JOURNAL OF HAEMATOLOGY
(2023)
Article
Hematology
George Goshua, Pranay Sinha, Jeanne E. Hendrickson, Christopher Tormey, Pavan K. Bendapudi, Alfred Ian Lee
Summary: The addition of caplacizumab to standard of care in acquired TTP treatment is not cost-effective due to the high cost of the medication and lack of improvement in relapse rates. Further study on the long-term impact of caplacizumab on health system cost is warranted.
Article
Hematology
I. Gomez-Segui, E. Frances Aracil, M. E. Mingot-Castellano, M. Vara Pampliega, R. Goterris Viciedo, F. Garcia Candel, C. Pascual Izquierdo, J. del Rio Garma, L. Guerra Dominguez, I. Vicuna Andres, J. Garcia-Arroba Peinado, S. Zalba Marcos, J. M. Vidan Estevez, E. Gonzalez Arias, V. Campuzano Saavedra, J. M. Garcia Gala, S. Ortega Sanchez, J. Martinez Nieto, L. Pardo Gambarte, M. Sole Rodriguez, M. Fernandez-Docampo, L. F. Avila Idrovo, L. Hernandez, J. Cid, J. de la Rubia Comos
Summary: The clinical characteristics and treatment response of immune thrombotic thrombocytopenic purpura (iTTP) in older patients were analyzed and compared with younger patients. Similar symptoms and laboratory results were observed in both groups, but older patients had a higher incidence of renal dysfunction. The frontline treatment and clinical outcomes did not differ between the two age groups. Notably, the use of caplacizumab and rituximab showed favorable safety and efficacy profiles in older patients.
BRITISH JOURNAL OF HAEMATOLOGY
(2023)
Article
Hematology
Oluwatobi Odetola, Karlyn A. Martin, Marie Dreyer, Priya Rajan, Anaadriana Zakarija, Brady L. Stein
Summary: Managing TTP in pregnancy can be challenging, especially if traditional treatments are ineffective. Off-label use of caplacizumab may be a reasonable option in refractory cases to achieve disease control and prevent maternal and fetal morbidity and mortality.
BRITISH JOURNAL OF HAEMATOLOGY
(2023)
Review
Genetics & Heredity
Sanober Nusrat, Kisha Beg, Osman Khan, Arpan Sinha, James George
Summary: Hereditary thrombotic thrombocytopenic purpura (hTTP), also known as Upshaw-Schulman syndrome, is a rare genetic disorder caused by mutations in the ADAMTS13 gene that leads to decreased or absent production of the plasma von Willebrand factor (VWF)-cleaving metalloprotease ADAMTS13. The disease can cause thrombocytopenia, impairment of blood circulation, and organ damage. Prophylaxis with plasma infusions or plasma-derived factor VIII products is the primary treatment for preventing acute episodes.
Article
Cell Biology
Jon Shaffer, Angela Grove
Summary: This case report demonstrates the efficacy of a second course of caplacizumab in a patient with relapsed TTP, showing significant improvement in platelet count. The patient was able to complete the treatment successfully without complications or further relapses.
Review
Hematology
X. Long Zheng
Summary: For immune thrombotic thrombocytopenic purpura (iTTP), the triple therapy consisting of therapeutic plasma exchange, caplacizumab, and immunosuppressives has been proven to be an effective treatment for acute episodes, accelerating platelet count normalization, reducing ICU and hospital stays, and most importantly, lowering mortality rate.
JOURNAL OF THROMBOSIS AND HAEMOSTASIS
(2021)
Review
Hematology
Gaelle Becel, Sylvia Faict, Adrien Picod, Raida Bouzid, Agnes Veyradier, Paul Coppo
Summary: The therapeutic landscape of thrombotic thrombocytopenic purpura (TTP) is rapidly evolving due to new targeted therapies, shifting from empiricism to pathophysiology-based treatments. International efforts have shed light on the epidemiology, clinical presentation, prognosis, and long-term outcome of this rare disease, providing high-quality results and practice changing studies for patient benefit. The most recent therapeutic findings have progressively improved the prognosis of TTP at both the acute phase and long-term outcome.
Article
Hematology
Tiago de Oliveira Boechat, Joao Samuel de Holanda Farias, Eduardo Flavio Oliveira Ribeiro, Michaela Larissa Lobo de Andrade
Summary: In this study, the treatment effect of caplacizumab in 5 Brazilian patients with acquired thrombotic thrombocytopenic purpura was observed. All patients achieved clinical remission and had good control of the disease with minimal side effects.
ANNALS OF HEMATOLOGY
(2023)
Review
Hematology
Charlotte Dekimpe, Elien Roose, Kazuya Sakai, Claudia Tersteeg, Simon F. De Meyer, Karen Vanhoorelbeke
Summary: Congenital thrombotic thrombocytopenic purpura (cTTP) is a rare disorder caused by a deficiency in ADAMTS-13. Current management involves plasma infusions of ADAMTS-13, but this is a demanding therapy with frequent allergic reactions. Gene therapy has the potential to provide a curative therapy for cTTP, and ongoing research is focused on various preclinical approaches. This review highlights the challenges of developing a gene therapy product for cTTP and provides an overview of the current state of preclinical gene therapy studies.
JOURNAL OF THROMBOSIS AND HAEMOSTASIS
(2023)
Article
Hematology
Kristi J. Smock
Summary: TTP is a life-threatening disorder that requires a combination of clinical information and laboratory results for diagnosis. ADAMTS13 activity and antibody testing are significant advancements in the field, but results may be challenging to interpret at times. Genetic testing for ADAMTS13 mutations can aid in the diagnosis of inherited TTP.
INTERNATIONAL JOURNAL OF LABORATORY HEMATOLOGY
(2021)
Review
Medicine, General & Internal
Adrien Joseph, Berangere S. Joly, Adrien Picod, Agnes Veyradier, Paul Coppo
Summary: Thrombotic thrombocytopenic purpura (TTP) is a rare and life-threatening thrombotic microangiopathy (TMA) associated with ADAMTS13 deficiency. The management of TTP can be challenging, especially in extreme ages of life. International cohorts of TTP patients report delayed diagnoses and misdiagnoses in children and elderly people. Child-onset TTP shares similarities with adult-onset TTP, while older TTP patients have atypical clinical presentations and poorer treatment responses.
JOURNAL OF CLINICAL MEDICINE
(2023)
Article
Urology & Nephrology
Caroline Kempf, Johannes Holle, Susanne Berns, Stephan Henning, Philip Bufler, Dominik Mueller
Summary: The safety of PEG insertion in pediatric PD patients can be improved by implementing a prophylactic antibiotic and antifungal regimen as well as modifying the PD program, which may help reduce the risk of peritonitis.
PERITONEAL DIALYSIS INTERNATIONAL
(2022)
Article
Medicine, General & Internal
Simon Moosburner, Leke Wiering, Safak Guel-Klein, Paul Ritschl, Tomasz Dziodzio, Nathanael Raschzok, Christian Witzel, Alexander Gratopp, Stephan Henning, Philip Bufler, Moritz Schmelzle, Georg Lurje, Wenzel Schoening, Johann Pratschke, Brigitta Globke, Robert oellinger
Summary: This study analyzed the short- and long-term outcomes of pediatric liver transplantation over a 30-year period. The results showed excellent long-term survival rates in pediatric patients undergoing liver transplantation. The improvement in patient survival can be attributed to advancements in surgical techniques, improved interdisciplinary collaboration, and better management of perioperative complications.
JOURNAL OF CLINICAL MEDICINE
(2022)
Article
Gastroenterology & Hepatology
Lucas Griessmair, Laura Pirringer, Steffeni Mountford, Andrea Sendelhofert, Marie-Christine Makeschin, Sibylle Koletzko, Doris Mayr, Philip Bufler
Summary: This study characterized the hepatic inflammatory infiltrate and expression of IL-37 in children with autoimmune liver diseases. IL-37 expression correlated positively with liver inflammation and fibrosis, the number of infiltrating immune cells, and serum markers for hepatic inflammation. IL-37 was mainly expressed in hepatocytes, cholangiocytes, and infiltrating immune cells. Additionally, IL-37 colocalized with intranuclear pSmad3L in areas of liver inflammation. These findings suggest that IL-37 may play a modulating role to limit hepatic inflammation and fibrosis in pediatric autoimmune liver diseases.
JOURNAL OF PEDIATRIC GASTROENTEROLOGY AND NUTRITION
(2022)
Article
Multidisciplinary Sciences
Maryam Ghalandary, Yue Li, Thomas Frohlich, Thomas Magg, Yanshan Liu, Meino Rohlfs, Sebastian Hollizeck, Raffaele Conca, Tobias Schwerd, Holm H. Uhlig, Philip Bufler, Sibylle Koletzko, Aleixo M. Muise, Scott B. Snapper, Fabian Hauck, Christoph Klein, Daniel Kotlarz
Summary: NOD2 polymorphisms may affect the perception of bacterial MDP and trigger inflammatory responses. A rare homozygous missense mutation in the first CARD domain of NOD2 was found in a patient with immunodeficiency and enteropathy. The mutation impaired NOD2-dependent signaling and proinflammatory cytokine production. The study also discovered that VCP is a novel interaction partner of NOD2, and VCP-mediated inflammatory responses upon ER stress are NOD2-dependent.
SCIENTIFIC REPORTS
(2022)
Letter
Gastroenterology & Hepatology
Eberhard Lurz, Dominic Lenz, Philip Bufler, Alexander Fichtner, Stephan Henning, Martin Jankofsky, Simone Kathemann, Michael Melter, Jun Oh, Eva Doreen Pfister, Ekkehard Sturm, Birgit Knoppke, Elke Lainka
JOURNAL OF HEPATOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Nikolaus Berndt, Christian A. Hudert, Johannes Eckstein, Christoph Loddenkemper, Stephan Henning, Philip Bufler, David Meierhofer, Ingolf Sack, Susanna Wiegand, Iwona Wallach, Hermann-Georg Holzhutter
Summary: This study used a mathematical model to analyze liver metabolism in children with NAFLD, showing significant alterations in carbohydrate, lipid, and ammonia metabolism that increase with obesity and NAFLD severity. NASH and IR have opposite associations with carbohydrate and lipid metabolism, while simultaneously decreasing urea synthesis and increasing glutamine release.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Biochemistry & Molecular Biology
Benedikt Fels, Arne Beyer, Violeta Cazana-Perez, Teresa Giraldez, Juan F. Navarro-Gonzalez, Diego Alvarez de la Rosa, Franz Schaefer, Aysun K. Bayazit, Lukasz Obrycki, Bruno Ranchin, Johannes Holle, Uwe Querfeld, Kristina Kusche-Vihrog
Summary: This study found that chronic kidney disease disrupts endothelial mechanics, leading to endothelial dysfunction. The data showed that serum from CKD patients increased the stiffness of the endothelial glycocalyx and cortex, while decreasing the height of the glycocalyx. Furthermore, the study found that serum from hemodialysis patients increased the expression of MR and the mechanical stiffness of the endothelial cortex, an effect that could be reversed by MR and ENaC antagonists.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Urology & Nephrology
Johannes Holle, Hendrik Bartolomaeus, Ulrike Loeber, Felix Behrens, Theda U. P. Bartolomaeus, Harithaa Anandakumar, Moritz I. I. Wimmer, Dai Long Vu, Mathias Kuhring, Ulrike Bruening, Andras Maifeld, Sabrina Geisberger, Stefan Kempa, Fabian Schumacher, Burkhard Kleuser, Philip Bufler, Uwe Querfeld, Stefanie Kitschke, Denise Engler, Leonard D. D. Kuhrt, Oliver Drechsel, Kai-Uwe Eckardt, Sofia K. K. Forslund, Andrea Thuermer, Victoria McParland, Jennifer A. A. Kirwan, Nicola Wilck, Dominik Mueller
Summary: Patients with chronic kidney disease (CKD) exhibit a proinflammatory immune response, potentially associated with gut dysbiosis, leading to gut barrier dysfunction and microbial metabolite imbalance, which significantly influences susceptibility to cardiovascular disease.
JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY
(2022)
Article
Multidisciplinary Sciences
Henrik Dimke, Camille Griveau, Wung-Man Evelyne Ling, Gaelle Brideau, Lydie Cheval, Pravina Muthan, Dominik Mueller, Amr Al-Shebel, Pascal Houillier, Caroline Prot-Bertoye
Summary: The kidney plays a critical role in maintaining mineral balance in the body. Dysregulation of calcium and magnesium reabsorption in the renal tubules can lead to familial hypomagnesemia with hypercalciuria and nephrocalcinosis (FHHNC), which is characterized by excessive wasting of calcium and magnesium. This study investigated the localization of claudin-19 (CLDN19), a protein involved in mineral reabsorption, in the kidneys and found that it is primarily located in the basolateral membrane of the renal tubules. Additionally, the study showed that CLDN19 interacts with claudin-16 (CLDN16) to regulate permeability in the tubules. These findings provide insights into the pathophysiology of FHHNC and highlight the importance of CLDN19 in maintaining mineral homeostasis in the kidney.
ANNALS OF THE NEW YORK ACADEMY OF SCIENCES
(2023)
Article
Gastroenterology & Hepatology
Aline Azabdaftari, Henrike L. L. Sczakiel, Magdalena Danyel, Benno Kohlmaier, Christoph J. J. Mache, Amelie Stalke, Eva-Doreen Pfister, Julia Thumfart, Stephan Henning, A. S. Knisely, Philip Bufler
Summary: Neonatal sclerosing cholangitis (NSC) is a liver disease associated with biliary fibrosis that often requires liver transplantation in childhood. Recent studies have discovered variants in the DCDC2 gene, which is involved in syndromic disease and NSC. This report presents four patients with hepatobiliary disease associated with novel variants in the DCDC2 gene, expanding the phenotypic spectrum of this disease. Testing for DCDC2 expression and variants should be considered in the evaluation of unknown cholangiopathy in childhood.
LIVER INTERNATIONAL
(2023)
Review
Biochemistry & Molecular Biology
Andre Maertens, Johannes Holle, Brit Mollenhauer, Andre Wegner, Jennifer Kirwan, Karsten Hiller
Summary: Untargeted metabolomics is a valuable tool in studying health and disease. However, instrumental drifts pose a challenge in generating high-quality data, and it is important to consider these variations during data processing. This article provides recommendations for an optimal data processing workflow and compares different batch-effect correction methods to improve data quality.
Article
Pediatrics
Norman Junge, Hanna Hentschel, Dorothee Krebs-Schmitt, Amelie Stalke, Eva-Doreen Pfister, Bjoern Hartleben, Martin Classen, Alexander Querfurt, Veronika Muench, Philip Bufler, Jun Oh, Enke Grabhorn
Summary: A study found that patients with mild Crigler-Najjar Syndrome (CNS) carrying the c.115C>G variant have a higher risk of progressive liver disease, despite having a very mild CNS phenotype. Currently, there are no identifiable predictors or causes for disease progression, but close follow-up can help identify patients with progressive liver disease at an early stage.
Article
Immunology
Laura Kroehn, Aline Azabdaftari, Julian Heuberger, Christian Hudert, Matthias Zilbauer, Tilman Breiderhoff, Philip Bufler
Summary: IL-37 plays its anti-inflammatory role in the intestines mainly by protecting the intestinal epithelial integrity through lamina propria immune cells.
FRONTIERS IN IMMUNOLOGY
(2023)