6 results on '"Behrens EM"'
Search Results
2. Adenovirus is Not Detected in Liver Tissue From a Historical Multicenter Cohort of Children With Acute Liver Failure.
- Author
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Chapin CA, Diamond T, Harris RM, Vaccaro O, Loomes KM, Alonso EM, and Behrens EM
- Subjects
- Child, Humans, Adenoviridae, Acute Disease, Liver Failure, Acute diagnosis, Liver Failure, Acute etiology, Hepatitis complications
- Abstract
There has been a recent surge in cases of pediatric acute hepatitis and pediatric acute liver failure (PALF) of unknown cause. Several reports have described clusters of these children who were positive for adenovirus (AdV) DNA, primarily in peripheral blood but some in liver tissue. We tested archived liver tissue specimens from a historical cohort of 44 children with PALF who were enrolled in a multicenter biorepository between 2007 and 2014 for AdV 40/41 using quantitative polymerase chain reaction. Most children had final diagnosis indeterminate. All samples were negative. Our findings suggest that AdV was unlikely to be an unidentified cause of indeterminate PALF during this past era. The significance of AdV viremia in contemporary cohorts of children with PALF remains unknown and requires further study., Competing Interests: The authors report no conflicts of interest., (Copyright © 2023 by European Society for European Society for Pediatric Gastroenterology, Hepatology, and Nutrition and North American Society for Pediatric Gastroenterology, Hepatology, and Nutrition.)
- Published
- 2023
- Full Text
- View/download PDF
3. The Liver in Hemophagocytic Lymphohistiocytosis: Not an Innocent Bystander.
- Author
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Diamond T, Bennett AD, and Behrens EM
- Subjects
- Humans, Cytokine Release Syndrome complications, Liver metabolism, CD8-Positive T-Lymphocytes metabolism, Lymphohistiocytosis, Hemophagocytic complications, Lymphohistiocytosis, Hemophagocytic diagnosis
- Abstract
Hemophagocytic lymphohistiocytosis (HLH) is a rare multisystemic hyperinflammatory disease commonly associated with hepatic dysfunction. Liver injury is mediated by unchecked antigen presentation, hypercytokinemia, dysregulated cytotoxicity by natural killer and CD8 T cells, and disruption of intrinsic hepatic metabolic pathways. Over the past decade, there have been significant advances in diagnostics and expansion in therapeutic armamentarium for this disorder allowing for improved morbidity and mortality. This review discusses the clinical manifestations and pathogenesis of HLH hepatitis in both familial and secondary forms. It will review growing evidence that the intrinsic hepatic response to hypercytokinemia in HLH perpetuates disease progression and the novel therapeutic approaches for patients with HLH-hepatitis/liver failure., Competing Interests: T.D. was supported by the National Center for Advancing Translational Sciences of the National Institutes of Health under award number KL2TR001879. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. T.D. and A.D.B. were supported by the Fred and Suzanne Biesecker Pediatric Liver Center at Children’s Hospital of Philadelphia. The remaining authors report no conflicts of interest., (Copyright © 2023 by European Society for European Society for Pediatric Gastroenterology, Hepatology, and Nutrition and North American Society for Pediatric Gastroenterology, Hepatology, and Nutrition.)
- Published
- 2023
- Full Text
- View/download PDF
4. Activated CD8 T-cell Hepatitis in Children With Indeterminate Acute Liver Failure: Results From a Multicenter Cohort.
- Author
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Chapin CA, Melin-Aldana H, Kreiger PA, Burn T, Neighbors K, Taylor SA, Ostilla L, Wechsler JB, Horslen SP, Leonis MA, Loomes KM, Behrens EM, Squires RH, and Alonso EM
- Subjects
- Adolescent, CD8-Positive T-Lymphocytes, Child, Child, Preschool, Cohort Studies, Humans, Infant, Pilot Projects, Hepatitis complications, Liver Failure, Acute complications, Liver Failure, Acute diagnosis, Liver Failure, Acute etiology
- Abstract
Objectives: In many pediatric acute liver failure (PALF) cases, a diagnosis is not identified, and the etiology is indeterminate (IND-PALF). Our pilot study found dense CD8 T-cell infiltrates and increased T-cell clonality in liver specimens from IND-PALF patients. We aimed to validate these findings in a multicenter cohort with investigators blinded to diagnosis., Methods: PALF Study Group registry subjects with IND-PALF (n = 37) and known diagnoses (DX-PALF) (n = 18), ages 1 to 17 years, with archived liver tissue were included. Liver tissue slides were stained for T cells (CD8 and CD4), B cells (CD20), macrophages (CD163), perforin, and tissue resident-memory T cells (Trm, CD103), and scored as minimal, moderate, or dense. Lymphocytes were isolated from frozen liver tissue for T-cell receptor beta (TCRβ) sequencing., Results: Dense hepatic CD8 staining was found in significantly more IND-PALF (n = 29, 78%) compared with DX-PALF subjects (n = 5, 28%) (P = 0.001). IND-PALF subjects were more likely to have dense or moderate perforin (88% vs 50%, P = 0.03) and CD103 (82% vs 40%, P = 0.02) staining compared with DX-PALF subjects. TCRβ sequencing of 15 IND-PALF cases demonstrated increased clonal overlap compared with 6 DX-PALF cases (P = 0.002)., Conclusions: Dense infiltration of effector Trm CD8 T cells characterizes liver tissue from IND-PALF subjects. Increased clonality suggests the T-cell expansion is antigen(s)-driven as opposed to a nonspecific inflammatory response. These findings support CD8 staining as a new biomarker of the activated CD8 T-cell PALF phenotype. Future studies are needed to characterize potential antigens, host risk factors, and inflammatory pathways with the goal of developing targeted therapies.
- Published
- 2020
- Full Text
- View/download PDF
5. Distinguishing Multisystem Inflammatory Syndrome in Children From Kawasaki Disease and Benign Inflammatory Illnesses in the SARS-CoV-2 Pandemic.
- Author
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Corwin DJ, Sartori LF, Chiotos K, Odom John AR, Cohn K, Bassiri H, Behrens EM, Teachey DT, Henrickson SE, Diorio CJ, Zorc JJ, and Balamuth F
- Subjects
- Adolescent, COVID-19, Child, Coronavirus Infections epidemiology, Coronavirus Infections therapy, Diagnosis, Differential, Female, Humans, Male, Pneumonia, Viral epidemiology, Pneumonia, Viral therapy, Retrospective Studies, SARS-CoV-2, Betacoronavirus, Coronavirus Infections diagnosis, Critical Care methods, Disease Management, Mucocutaneous Lymph Node Syndrome diagnosis, Pandemics, Pneumonia, Viral diagnosis
- Abstract
Objective: The aim of the study was to compare presenting clinical and laboratory features among children meeting the surveillance definition for multisystem inflammatory syndrome in children (MIS-C) across a range of illness severities., Methods: This is a retrospective single-center study of patients younger than 21 years presenting between March 1 and May 15, 2020. Included patients met the Centers for Disease Control and Prevention criteria for MIS-C (inflammation, fever, involvement of 2 organ systems, lack of alternative diagnoses). We defined 3 subgroups by clinical outcomes: (1) critical illness requiring intensive care interventions; (2) patients meeting Kawasaki disease (KD) criteria but not requiring critical care; and (3) mild illness not meeting either criteria. A comparator cohort included patients with KD at our institution during the same time frame in 2019., Results: Thirty-three patients were included (5, critical; 8, 2020 KD; 20, mild). The median age for the critical group was 10.9 years (2.7 for 2020 KD; 6.0 for mild, P = 0.033). The critical group had lower median absolute lymphocyte count (850 vs 3005 vs 2940/uL, P = 0.005), platelets (150 vs 361 vs 252 k/uL, P = 0.005), and sodium (129 vs 136 vs 136 mmol/L, P = 0.002), and higher creatinine (0.7 vs 0.2 vs 0.3 mg/dL, P = 0.002). In the critical group, 60% required vasoactive medications, and 40% required mechanical ventilation. Clinical and laboratories features were similar between the 2020 and 2019 KD groups., Conclusions: We describe 3 groups with inflammatory syndromes during the SARS-CoV-2 pandemic. The initial profile of lymphopenia, thrombocytopenia, hyponatremia, and abnormal creatinine may help distinguish critically ill MIS-C patients from classic/atypical KD or more benign acute inflammation.
- Published
- 2020
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6. BIRC4 Mutation: An Important Rare Cause of Uveitis.
- Author
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Basiaga ML, Weiss PF, and Behrens EM
- Subjects
- Antirheumatic Agents administration & dosage, Child, Humans, Male, Mutation, Treatment Outcome, X-Linked Inhibitor of Apoptosis Protein genetics, Adalimumab administration & dosage, Cyclosporine administration & dosage, Epstein-Barr Virus Infections complications, Genetic Diseases, X-Linked diagnosis, Genetic Diseases, X-Linked drug therapy, Genetic Diseases, X-Linked genetics, Genetic Diseases, X-Linked physiopathology, Lymphohistiocytosis, Hemophagocytic diagnosis, Lymphohistiocytosis, Hemophagocytic etiology, Lymphoproliferative Disorders diagnosis, Lymphoproliferative Disorders drug therapy, Lymphoproliferative Disorders genetics, Lymphoproliferative Disorders physiopathology, Uveitis diagnosis, Uveitis drug therapy, Uveitis etiology, Uveitis physiopathology, X-Linked Inhibitor of Apoptosis Protein deficiency
- Abstract
We report a 6-year-old man with chronic severe recalcitrant bilateral anterior uveitis and a remote history of hemophagocytic lymphocytic histiocytosis secondary to Epstein-Barr virus infection. The patient was treated for idiopathic uveitis after an initial extensive evaluation failed to reveal a specific diagnosis. The patient failed to achieve sustained inactive disease with multiple monotherapies including topical glucocorticoid, methotrexate, infliximab, mycophenolate mofeti, and cyclosporine. Disease control was finally attained with a combination of cyclosporine and adalimumab. After more recent testing, he was found to have a novel deletion on the BIRC4 (baclovirus inhibitor of apoptosis repeat containing protein 4) gene, the causative gene for X-linked lymphoproliferative syndrome type 2. We conclude that male patients with chronic idiopathic uveitis should be questioned about a history of hemophagocytic lymphocytic histiocytosis during their workup and screened for BIRC4 mutation if appropriate.
- Published
- 2015
- Full Text
- View/download PDF
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