Publications by authors named "Adam DuVall"

7 Publications

  • Page 1 of 1

Validation and clinical application of transactivation assays for RUNX1 variant classification.

Blood Adv 2022 Jan 13. Epub 2022 Jan 13.

Hannover Medical School, Hannover, Germany.

Familial platelet disorder with associated myeloid malignancies (RUNX1-FPD) is caused by heterozygous pathogenic germline variants of RUNX1. In the present study, we evaluate the applicability of transactivation assays to investigate RUNX1 variants in different regions of the protein. We studied 11 variants to independently validate transactivation assays supporting variant classification following the ClinGen Myeloid Malignancies variant curation expert panel guidelines. Variant classification is key for the translation of genetic findings. We showed that new assays need to be developed to assess C-terminal RUNX1 variants. Two variants of uncertain significance (VUS) were reclassified to likely pathogenic. Additionally, our analyses supported the (likely) pathogenic classification of two other variants. We demonstrated functionality of four VUS, but reclassification to (likely) benign was challenging and suggested the need to reevaluate current classification guidelines. Finally, clinical utility of our assays was illustrated in the context of seven families. Our data confirmed RUNX1-FPD suspicion in three families with RUNX1-FPD-specific family history. Whereas for three variants identified in non RUNX1-FPD-typical families, no functional defect was detected. Applying functional assays to support RUNX1 variant classification can be essential for adequate care of index patients and their relatives at risk. It facilitates translation of genetic data into personalized medicine.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1182/bloodadvances.2021006161DOI Listing
January 2022

Examining the Pathoplastic Moderating Role of Education on the Association between Depressive Mood and Self-Rated Health among Cancer Survivors: A Population-Based Study.

Curr Oncol 2021 10 11;28(5):4042-4052. Epub 2021 Oct 11.

Department of Medicine, University of Chicago, Chicago, IL 60637, USA.

Objective: Self-rated health (SRH) is a salient patient outcome for cancer survivors, and depressive mood and education are known determinants of cancer survivors' SRH. Moving beyond the well-established direct association between depressive mood, education, and SRH among cancer survivors, this epidemiological study investigated the pathoplastic role of education on depressive mood in relation to SRH among a nationally representative sample of cancer survivors in the United States.

Methods: The 2019 National Health Interview Survey was analyzed using data from adult participants (≥18 years old) who self-reported as cancer survivors ( = 3844). Ordered logistic regression was used to evaluate the direct impact of depressive mood and education in relation to SRH. In addition, the pathoplastic moderating effect was evaluated using ordered logistic regression with an interaction term of depressive mood and education in the regression model. All analyses adjusted for complex sample weights so that findings are nationally representative.

Results: After adjusting for all covariates, U.S. cancer survivors' depressive mood was significantly associated with lower SRH, and U.S. cancer survivors' higher education was significantly associated with higher SRH. As a pathoplastic moderator, cancer survivors' education significantly moderated the association between depressive mood and SRH. The negative association between depressive mood and SRH was significantly greater among those with higher education.

Conclusion: Moving beyond the direct association between depressive mood, education, and SRH, education served as a pathoplastic moderator in relation to depressive mood and SRH. Psycho-oncology providers need to be mindful of the "protective-risk" effect of education in relation to cancer survivors' depressive mood and SRH.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3390/curroncol28050343DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8534924PMC
October 2021

Solution-focused brief therapy for adolescent and young adult cancer patients in China: a pilot randomized controlled trial.

J Psychosoc Oncol 2021 Jul 7:1-18. Epub 2021 Jul 7.

Department of Medicine, University of Chicago, Chicago, IL, USA.

Objective: This pilot clinical trial investigated solution-focused brief therapy (SFBT) for psychological distress among adolescent and young adult (AYA) patients with cancer in China.

Methods: Fifty Chinese AYA patients diagnosed with cancer were randomized into the treatment group (SFBT) and control group (active control). Psychological distress was measured by the brief symptom inventory and hope was measured by the Herth-Hope-Index. Treatment effects were analyzed using analysis-of-covariance and between-group small-sample-size corrected Hedges' .

Results: The results indicated that SFBT resulted in a significant reduction in the psychological distress and improvement in hope of AYA patients with cancer. Analyses of the 4-week posttreatment score suggest the short-term sustainability of SFBT for psychological distress among AYAs diagnosed with cancer.

Conclusions And Implications: This study has demonstrated that SFBT's impact is statistically significant and clinically meaningful. The inclusion of positive emotions, i.e., hope, as part of the investigation also highlighted the significance of promoting positive emotions among AYA patients with cancer.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1080/07347332.2021.1931627DOI Listing
July 2021

Levocarnitine for asparaginase-induced hepatic injury: a multi-institutional case series and review of the literature.

Leuk Lymphoma 2018 10 12;59(10):2360-2368. Epub 2018 Feb 12.

g Department of Radiation Medicine , Oregon Health and Science University , Portland , OR , USA.

Asparaginase, an important treatment component for acute lymphoblastic leukemia (ALL), causes severe hepatotoxicity in some patients. Levocarnitine is a mitochondrial co-factor that can potentially ameliorate the mitochondrial toxicity of asparaginase. In this retrospective case series, we describe the clinical presentation and management of six pediatric and young adult patients (mean age 12.7, range 9-24 years) with ALL who developed Grade 3-4 hyperbilirubinemia following administration of asparaginase as part of induction/re-induction therapy. Five of these patients were treated with levocarnitine with subsequent improvement of hyperbilirubinemia, while one patient was given levocarnitine prophylactically during induction and developed Grade 3 hyperbilirubinemia, but did not require therapy adjustments or delays. Increased awareness in the pediatric oncology community regarding asparaginase-associated hepatic toxicity and the potential role of levocarnitine in management is warranted.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1080/10428194.2018.1435873DOI Listing
October 2018

Hematologic Manifestations of Deficiency of Adenosine Deaminase 2 (DADA2) and Response to Tumor Necrosis Factor Inhibition in DADA2-Associated Bone Marrow Failure.

J Clin Immunol 2018 02 6;38(2):166-173. Epub 2018 Feb 6.

Pediatrics and Communicable Diseases, Pediatric Hematology/Oncology, University of Michigan, 1500 E. Medical Center Drive, D4202 Medical Professional Building, Ann Arbor, MI, 48109, USA.

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s10875-018-0480-4DOI Listing
February 2018

Age-Stratified Profiles of Serum IL-6, IL-10, and TNF-α Cytokines Among Kenyan Children with Schistosoma haematobium, Plasmodium falciparum, and Other Chronic Parasitic Co-Infections.

Am J Trop Med Hyg 2015 May 9;92(5):945-51. Epub 2015 Mar 9.

Center for Global Health and Diseases, Case Western Reserve University School of Medicine, Cleveland, Ohio; Institute of Immunity and Infection, St. George's University of London, London, United Kingdom; Division of Vector Borne and Neglected Tropical Diseases, Ministry of Public Health and Sanitation, Nairobi, Kenya; Department of Environmental Sciences, Emory University, Atlanta, Georgia.

In a study of children having polyparasitic infections in a Schistosoma haematobium-endemic area, we examined the hypothesis that S. haematobium-positive children, compared with S. haematobium-negative children (anti-soluble worm antigen preparation [SWAP] negative and egg negative) have increased systemic production of pro-inflammatory cytokines (interleukin [IL]-6, tumor necrosis factor [TNF]-α) and decreased down-regulatory IL-10. A total of 804 children, 2-19 years of age, were surveyed between July and December 2009 and tested for S. haematobium, Plasmodium falciparum, filariasis, and soil-transmitted helminth infections. Plasma levels of IL-6, TNF-α, and IL-10 were compared for S. haematobium-positive and S. haematobium-negative children, adjusting for malaria, filaria, and hookworm co-infections, and for nutritional status, age group, sex, and geographic location. IL-10 was significantly elevated among children infected with S. haematobium, showing bimodal peaks in 7-8 and 13-14 years age groups. IL-10 was also higher among children who were acutely malnourished, whereas IL-10 levels were lower in the presence of S. haematobium-filaria co-infection. After adjustment for co-factors, IL-6 was significantly elevated among children of 5-6 years and among those with P. falciparum infection. Lower levels of IL-6 were found in malaria-hookworm co-infection. High levels of TNF-α were found in children aged 11-12 years regardless of infection status. In addition, village of residence was a strong predictor of IL-6 and IL-10 plasma levels. In adolescent children infected with S. haematobium, there is an associated elevation in circulating IL-10 that may reduce the risk of later morbidity. Although we did not find a direct link between S. haematobium infection and circulating pro-inflammatory IL-6 and TNF-α levels, future T-cell stimulation studies may provide more conclusive linkages between infection and cytokine responses in settings that are endemic for multiple parasites and multiple co-infections.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.4269/ajtmh.14-0444DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4426583PMC
May 2015

Development of a specimen-sparing multichannel bead assay to detect antiparasite IgG4 for the diagnosis of Schistosoma and Wuchereria infections on the coast of Kenya.

Am J Trop Med Hyg 2014 Apr 10;90(4):638-45. Epub 2014 Feb 10.

Center for Global Health and Diseases, Case Western Reserve University School of Medicine, Cleveland, Ohio; Division of Vector Borne and Neglected Tropical Diseases, Ministry of Public Health and Sanitation, Nairobi, Kenya; Department of Environmental Sciences, Emory University, Atlanta, Georgia.

To better delineate the impact of parasitic coinfection in coastal Kenya, we developed a novel specimen-sparing bead assay using multiplex flow immunoassay (MFI) technology to simultaneously measure serum or plasma immunoglobulin G4 (IgG4) against Brugia malayi antigen (BMA) and Schistosoma haematobium soluble worm antigen (SWAP). Properties of the bead assay were estimated by latent class analysis using data from S. haematobium egg counts/filarial rapid diagnostic cards (RDTs), parasite-specific enzyme-linked immunosorbent assays (ELISAs), and the multichannel IgG4 assay. For schistosomiasis, the bead assay had an estimated sensitivity of 81% and a specificity of 45%, and it was more sensitive than ELISA or urine egg counts for diagnosing infection. For filariasis, it had a sensitivity of 86% and a specificity of 39%, and it was more sensitive than ELISA or RDT. Measuring antibody by MFI is feasible and may provide more accurate epidemiological information than current parasitological tests, especially in the setting of low-intensity infections.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.4269/ajtmh.13-0292DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3973507PMC
April 2014
-->