Browsing by Author "Skiles, Jodi L."

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    Chaplain care in pediatric oncology: Insight for interprofessional collaboration
    (Wiley, 2019-12) Lion, Alex H.; Skiles, Jodi L.; Newton Watson, Beth; Young, J. Daniel; Torke, Alexia M.; Pediatrics, School of Medicine
    Background Although attending to spiritual and religious needs is part of high quality care of pediatric cancer patients, oncology clinicians may not understand the role of the chaplain, resulting in underutilization of resources and failure to fully integrate the chaplain into the clinical team. We provide a description of what the chaplain does in the care of pediatric oncology patients. Methods We conducted a qualitative content analysis of chaplain chart notes over a one‐year period on the pediatric oncology service at a freestanding children's hospital. Using criteria designed to capture multiple potential factors in chaplain referral, we selected 30 patients for thematic analysis. Results In 2016, 166 pediatric patients were diagnosed with cancer and received ongoing care at our institution. From the 30 patients selected, 230 chaplain encounters were documented in the medical chart. Three major themes emerged. (1) The chaplains provided a rich description of spiritual and psychosocial aspects of the patient and family's experience; (2) chaplains provided diverse interventions, both religious and secular in nature; and (3) chaplains provided care within a longitudinal relationship. All three themes depend on the empathic listening by a chaplain. Conclusions The chaplains’ observations about patient and family beliefs, experiences, and emotional/spiritual states have the potential to inform the interdisciplinary care of the patient. Chaplain documentation provides insight into how spiritual care interventions and close relationships may promote patient and family well‐being. In future work, we will explore how to give voice to their insights in caring for pediatric oncology patients.
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    CYP3A5 genotype and its impact on vincristine pharmacokinetics and development of neuropathy in Kenyan children with cancer
    (Wiley, 2018-03) Skiles, Jodi L.; Chiang, ChienWei; Li, Claire H.; Martin, Steve; Smith, Ellen L.; Olbara, Gilbert; Jones, David R.; Vik, Terry A.; Mostert, Saskia; Abbink, Floor; Kaspers, Gertjan J.; Li, Lang; Njuguna, Festus; Sajdyk, Tammy J.; Renbarger, Jamie L.; Pediatrics, School of Medicine
    BACKGROUND: Vincristine (VCR) is a critical part of treatment in pediatric malignancies and is associated with dose-dependent peripheral neuropathy (vincristine-induced peripheral neuropathy [VIPN]). Our previous findings show VCR metabolism is regulated by the CYP3A5 gene. Individuals who are low CYP3A5 expressers metabolize VCR slower and experience more severe VIPN as compared to high expressers. Preliminary observations suggest that Caucasians experience more severe VIPN as compared to nonCaucasians. PROCEDURE: Kenyan children with cancer who were undergoing treatment including VCR were recruited for a prospective cohort study. Patients received IV VCR 2 mg/m2 /dose with a maximum dose of 2.5 mg as part of standard treatment protocols. VCR pharmacokinetics (PK) sampling was collected via dried blood spot cards and genotyping was conducted for common functional variants in CYP3A5, multi-drug resistance 1 (MDR1), and microtubule-associated protein tau (MAPT). VIPN was assessed using five neuropathy tools. RESULTS: The majority of subjects (91%) were CYP3A5 high-expresser genotype. CYP3A5 low-expresser genotype subjects had a significantly higher dose and body surface area normalized area under the curve than CYP3A5 high-expresser genotype subjects (0.28 ± 0.15 hr·m2 /l vs. 0.15 ± 0.011 hr·m2 /l, P = 0.027). Regardless of which assessment tool was utilized, minimal neuropathy was detected in this cohort. There was no difference in the presence or severity of neuropathy assessed between CYP3A5 high- and low-expresser genotype groups. CONCLUSION: Genetic factors are associated with VCR PK. Due to the minimal neuropathy observed in this cohort, there was no demonstrable association between genetic factors or VCR PK with development of VIPN. Further studies are needed to determine the role of genetic factors in optimizing dosing of VCR for maximal benefit.
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    Low serum albumin levels prior to pediatric allogeneic HCT are associated with increased need for critical care interventions and increased 6-month mortality
    (Wiley, 2017-09) Teagarden, Alicia M.; Skiles, Jodi L.; Beardsley, Andrew L.; Hobson, Michael J.; Moser, Elizabeth A. S.; Renbarger, Jamie L.; Rowan, Courtney M.; Pediatrics, School of Medicine
    Poor nutritional status in HCT patients is a negative prognostic factor. There are no pediatric studies evaluating albumin levels prior to HCT and need for critical care interventions. We hypothesized that pediatric patients with low albumin levels, routinely measured 30 days (±10 days) prior to allogeneic HCT, have a higher risk of critical care interventions in the post-transplant period. We performed a 5-year retrospective study of pediatric patients who underwent allogeneic HCT for any indication. Patients were categorized based on albumin level. Hypoalbuminemia was defined as <3.1 g/dL. A total of 73 patients were included, with a median age of 7.4 years (IQR 3.3, 13.2). Patients with hypoalbuminemia had higher needs for critical care interventions including non-invasive ventilation (44% vs 8%, P=.01), mechanical ventilation (67% vs 17%, P<.01), and vasoactive therapy (56% vs 16%, P=.01). Patients with hypoalbuminemia also had a higher 6-month mortality (56% vs 17%, P=.02). Our data demonstrate that children undergoing allogeneic HCT with hypoalbuminemia in the pretransplant period are more likely to require critical care interventions and have higher 6-month mortality. These findings identify an at-risk population in which nutritional improvements may be instituted prior to HCT in hopes of improving outcomes.
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    A Metabolomics Approach for Early Prediction of Vincristine-Induced Peripheral Neuropathy
    (Springer, 2020-04-15) Verma, Parul; Devaraj, Jayachandran; Skiles, Jodi L.; Sajdyk, Tammy; Ho, Richard H.; Hutchinson, Raymond; Wells, Elizabeth; Li, Lang; Renbarger, Jamie; Cooper, Bruce; Ramkrishna, Doraiswami; Pediatrics, School of Medicine
    Vincristine is a core chemotherapeutic drug administered to pediatric acute lymphoblastic leukemia patients. Despite its efficacy in treating leukemia, it can lead to severe peripheral neuropathy in a subgroup of the patients. Peripheral neuropathy is a debilitating and painful side-effect that can severely impact an individual’s quality of life. Currently, there are no established predictors of peripheral neuropathy incidence during the early stage of chemotherapeutic treatment. As a result, patients who are not susceptible to peripheral neuropathy may receive sub-therapeutic treatment due to an empirical upper cap on the dose, while others may experience severe neuropathy at the same dose. Contrary to previous genomics based approaches, we employed a metabolomics approach to identify small sets of metabolites that can be used to predict a patient’s susceptibility to peripheral neuropathy at different time points during the treatment. Using those identified metabolites, we developed a novel strategy to predict peripheral neuropathy and subsequently adjust the vincristine dose accordingly. In accordance with this novel strategy, we created a free user-friendly tool, VIPNp, for physicians to easily implement our prediction strategy. Our results showed that focusing on metabolites, which encompasses both genotypic and phenotypic variations, can enable early prediction of peripheral neuropathy in pediatric leukemia patients.
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    The National Physicians Cooperative: transforming fertility management in the cancer setting and beyond.
    (Future Medicine, 2018-12) Smith, Brigid M.; Duncan, Francesca E.; Ataman, Lauren; Smith, Kristin; Quinn, Gwendolyn P.; Chang, R. Jeffrey; Finlayson, Courtney; Orwig, Kyle; Valli-Pulaski, Hanna; Moravek, Molly B.; Zelinski, Mary B.; Irene Su, H.; Vitek, Wendy; Smith, James F.; Jeruss, Jacqueline S.; Gracia, Clarisa; Coutifaris, Christos; Shah, Divya; Nahata, Leena; Gomez-Lobo, Veronica; Appiah, Leslie Coker; Brannigan, Robert E.; Gillis, Valerie; Gradishar, William; Javed, Asma; Rhoton-Vlasak, Alice S.; Kondapalli, Laxmi A.; Neuber, Evelyn; Ginsberg, Jill P.; Muller, Charles H.; Hirshfeld-Cytron, Jennifer; Kutteh, William H.; Lindheim, Steven R.; Cherven, Brooke; Meacham, Lillian R.; Rao, Pooja; Torno, Lilibeth; Sender, Leonard S.; Vadaparampil, Susan T.; Skiles, Jodi L.; Schafer-Kalkhoff, Tara; Frias, Oliva J.; Byrne, Julia; Westphal, Lynn M.; Schust, Danny J.; Klosky, James L.; McCracken, Kate A.; Ting, Alison; Khan, Zaraq; Granberg, Candace; Lockart, Barbara; Scoccia, Bert; Laronda, Monica M.; Mersereau, Jennifer E.; Marsh, Courtney; Pavone, Mary Ellen; Woodruff, Teresa K.; Pediatrics, School of Medicine
    Once unimaginable, fertility management is now a nationally established part of cancer care in institutions, from academic centers to community hospitals to private practices. Over the last two decades, advances in medicine and reproductive science have made it possible for men, women and children to be connected with an oncofertility specialist or offered fertility preservation soon after a cancer diagnosis. The Oncofertility Consortium's National Physicians Cooperative is a large-scale effort to engage physicians across disciplines - oncology, urology, obstetrics and gynecology, reproductive endocrinology, and behavioral health - in clinical and research activities to enable significant progress in providing fertility preservation options to children and adults. Here, we review the structure and function of the National Physicians Cooperative and identify next steps.
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    Outcomes of Pediatric Patients with Therapy-Related Myeloid Neoplasms
    (Springer Nature, 2021) Sharma, Akshay; Huang, Sujuan; Li, Ying; Brooke, Russell J.; Ahmed, Ibrahim; Allewelt, Heather B.; Amrolia, Persis; Bertaina, Alice; Bhatt, Neel S.; Bierings, Marc B.; Bies, Joshua; Brisset, Claire; Brondon, Jennifer E.; Dahlberg, Ann; Dalle, Jean-Hugues; Eissa, Hesham; Fahd, Mony; Gassas, Adam; Gloude, Nicholas J.; Goebel, W. Scott; Goeckerman, Erika S.; Harris, Katherine; Ho, Richard; Hudspeth, Michelle P.; Huo, Jeffrey S.; Jacobsohn, David; Kasow, Kimberly A.; Katsanis, Emmanuel; Kaviany, Saara; Keating, Amy K.; Kernan, Nancy A.; Ktena, Yiouli P.; Lauhan, Colette R.; López-Hernandez, Gerardo; Martin, Paul L.; Myers, Kasiani C.; Naik, Swati; Olaya-Vargas, Alberto; Onishi, Toshihiro; Radhi, Mohamed; Ramachandran, Shanti; Ramos, Kristie; Rangarajan, Hemalatha G.; Roehrs, Philip A.; Sampson, Megan E.; Shaw, Peter J.; Skiles, Jodi L.; Somers, Katherine; Symons, Heather J.; de Tersant, Marie; Uber, Allison N.; Versluys, Birgitta; Cheng, Cheng; Triplett, Brandon M.; Pediatrics, School of Medicine
    Long-term outcomes after allogeneic hematopoietic cell transplantation (HCT) for therapy-related myeloid neoplasms (tMNs) are dismal. There are few multicenter studies defining prognostic factors in pediatric patients with tMNs. We have accumulated the largest cohort of pediatric patients who have undergone HCT for a tMN to perform a multivariate analysis defining factors predictive of long-term survival. Sixty-eight percent of the 401 patients underwent HCT using a myeloablative conditioning (MAC) regimen, but there were no statistically significant differences in the overall survival (OS), event-free survival (EFS), or cumulative incidence of relapse and non-relapse mortality based on the conditioning intensity. Among the recipients of MAC regimens, 38.4% of deaths were from treatment-related causes, especially acute graft versus host disease (GVHD) and end-organ failure, as compared to only 20.9% of deaths in the reduced-intensity conditioning (RIC) cohort. Exposure to total body irradiation (TBI) during conditioning and experiencing grade III/IV acute GVHD was associated with worse OS. In addition, a diagnosis of therapy-related myelodysplastic syndrome and having a structurally complex karyotype at tMN diagnosis were associated with worse EFS. Reduced-toxicity (but not reduced-intensity) regimens might help to decrease relapse while limiting mortality associated with TBI-based HCT conditioning in pediatric patients with tMNs.
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    Prospective assessment of risk biomarkers of sinusoidal obstruction syndrome after hematopoietic cell transplantation
    (The American Society for Clinical Investigation, 2023-05-22) Han, Yan; Bidgoli, Alan; DePriest, Brittany P.; Méndez, Alejandra; Bijangi-Vishehsaraei, Khadijeh; Perez-Albuerne, Evelio D.; Krance, Robert A.; Renbarger, Jamie; Skiles, Jodi L.; Choi, Sung W.; Liu, Hao; Paczesny, Sophie; Biostatistics and Health Data Science, School of Medicine
    BACKGROUND: Currently, no laboratory tests exist to stratify for the risk of developing sinusoidal obstruction syndrome (SOS), an early endothelial complication after hematopoietic cell transplantation (HCT). Risk biomarkers of SOS have not been verified in a prospective cohort accounting for differences between practices across institutions. Herein, we aimed to define risk groups for SOS occurrence using 3 proteins: L-ficolin, hyaluronic acid (HA), and stimulation 2 (ST2). METHODS: Between 2017 and 2021, we prospectively accrued 80 pediatric patients across 4 US centers. Biomarkers were tested by ELISA blind to patient groupings and associated with SOS incidence on day 35 after HCT, and overall survival (OS) on day 100 after HCT. Cutpoints were identified using retrospective cohorts and applied to the prospective cohort. RESULTS: Combination of the 3 biomarkers measured on day 3 after HCT in the prospective cohort provided 80% (95% CI 55%–100%) sensitivity and 73% (95% CI 62%–83%) specificity for risk of SOS occurrence. Patients with low L-ficolin were 9 times (95% CI 3–32) more likely to develop SOS, while patients with high HA and ST2 were 6.5 (95% CI 1.9–22.0) and 5.5 (95% CI 2.3–13.1) times more likely to develop SOS. These 3 markers also predicted worse day 100 OS — L-ficolin: HR, 10.0 (95% CI 2.2–45.1), P = 0.0002; HA: HR, 4.1 (95% CI 1.0–16.4), P = 0.031; and ST2: HR, 3.9 (95% CI 0.9–16.4), P = 0.04. CONCLUSION: L-ficolin, HA, and ST2 levels measured as early as 3 days after HCT improved risk stratification for SOS occurrence and OS and may guide risk-adapted preemptive therapy.
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    Simultaneous Quantification of Vincristine and Its Major M1 Metabolite from Dried Blood Spot Samples of Kenyan Pediatric Cancer Patients by UPLC-MS/MS
    (Elsevier, 2021-09) Agu, Lorita; Skiles, Jodi L.; Masters, Andrea R.; Renbarger, Jamie L.; Chow, Diana S-L; Pediatrics, School of Medicine
    Vincristine (VCR) is an integral part of chemotherapy regimens in the US and in developing countries. There is a paucity of information about its disposition and optimal therapeutic dosing. VCR is preferentially metabolized to its major M1 metabolite by the polymorphic CYP3A5 enzyme, which may be clinically significant as CYP3A5 expression varies across populations. Thus, it is important to monitor both VCR and M1 and characterize their dispositions. A previously developed HPLC-MS/MS method for VCR quantification was not sensitive enough to quantify the M1 metabolite beyond 1 hr. post VCR dose (not published). Establishing a highly sensitive assay is a pre-requisite to simultaneously quantify and monitor VCR and M1, which will enable characterization of drug exposure and dispositions of both analytes in a pediatric cancer population. The addition of formic acid during the extraction process enhanced M1 extraction from DBS samples. A sensitive, accurate, and precise UPLC-MS/MS assay method for the simultaneous quantification of VCR and M1 from human dried blood spots (DBS) was developed and validated. Chromatographic separation was performed on Inertsil ODS-3 C18 column (5 μm, 3.0 x 150 mm). A gradient elution of mobile phase A (methanol-0.2% formic acid in water, 20:80 v/v) and mobile phase B (methanol-0.2% formic acid in water, 80:20 v/v) was used with a flow rate of 0.4 mL/min and a total run time of 5 min. The analytes were ionized by electrospray ionization in the positive ion mode. The linearity range for both analytes in DBS were 0.6-100 ng/ml for VCR and 0.4-100 ng/ml for M1. The intra- and inter-day accuracies for VCR and M1 were 93.10-117.17% and 95.88-111.21%, respectively. While their intra- and inter-day precisions were 1.05 to 10.11% and 5.78 to 8.91%, respectively. The extraction recovery of VCR from DBS paper was 35.3 – 39.4% and 10.4 – 13.4% for M1, with no carryover observed for both analytes. This is the first analytical method to report the simultaneous quantification of VCR and M1 from human DBS. For the first time, concentrations of M1 from DBS patient samples were obtained beyond 1 -h post VCR dose. The developed method was successfully employed to monitor both compounds and perform pharmacokinetic analysis in a population of Kenyan pediatric cancer patients.
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    A View from the past into our collective future: the oncofertility consortium vision statement
    (Springer, 2021-01) Woodruff, Teresa K.; Ataman-Millhouse, Lauren; Acharya, Kelly S.; Almeida-Santos, Teresa; Anazodo, Antoinette; Anderson, Richard A.; Appiah, Leslie; Bader, Joy; Becktell, Kerri; Brannigan, Robert E.; Breech, Lesley; Bourlon, Maria T.; Bumbuliene, Žana; Burns, Karen; Campo-Engelstein, Lisa; Campos, Jacira R.; Centola, Grace M.; Chehin, Mauricio Barbour; Chen, Diane; De Vos, Michel; Duncan, Francesca E.; El-Damen, Ahmed; Fair, Douglas; Famuyiwa, Yemi; Fechner, Patricia Y.; Fontoura, Paula; Frias, Olivia; Gerkowicz, Sabrina A.; Ginsberg, Jill; Gracia, Clarisa R.; Goldman, Kara; Gomez-Lobo, Veronica; Hazelrigg, Brent; Hsieh, Michael H.; Hoyos, Luis R.; Hoyos-Martinez, Alfonso; Jach, Robert; Jassem, Jacek; Javed, Murid; Jayasinghe, Yasmin; Jeelani, Roohi; Jeruss, Jacqueline S.; Kaul-Mahajan, Nalini; Keim-Malpass, Jessica; Ketterl, Tyler G.; Khrouf, Mohamed; Kimelman, Dana; Kusuhara, Atsuko; Kutteh, William H.; Laronda, Monica M.; Lee, Jung Ryeol; Lehmann, Vicky; Letourneau, Joseph M.; McGinnis, Lynda K.; McMahon, Eileen; Meacham, Lillian R.; Velez Mijangos, Monserrat Fabiola; Moravek, Molly; Nahata, Leena; Ogweno, George Moses; Orwig, Kyle E.; Pavone, Mary Ellen; Peccatori, Fedro Alessandro; Pesce, Romina Ileana; Pulaski, Hanna; Quinn, Gwendolyn; Quintana, Ramiro; Quintana, Tomas; de Carvalho, Bruno Ramalho; Ramsey-Goldman, Rosalind; Reinecke, Joyce; Reis, Fernando M.; Rios, Julie; Rhoton-Vlasak, Alice S.; Rodriguez-Wallberg, Kenny A.; Roeca, Cassandra; Rotz, Seth J.; Rowell, Erin; Salama, Mahmoud; Saraf, Amanda J.; Scarella, Anibal; Schafer-Kalkhoff, Tara; Schmidt, Deb; Senapati, Suneeta; Shah, Divya; Shikanov, Ariella; Shnorhavorian, Margarett; Skiles, Jodi L.; Smith, James F.; Smith, Kristin; Sobral, Fabio; Stimpert, Kyle; Su, H. Irene; Sugimoto, Kouhei; Suzuki, Nao; Thakur, Mili; Victorson, David; Viale, Luz; Vitek, Wendy; Wallace, W. Hamish; Wartella, Ellen A.; Westphal, Lynn M.; Whiteside, Stacy; Wilcox, Lea H.; Wyns, Christine; Xiao, Shuo; Xu, Jing; Zelinski, Mary; Pediatrics, School of Medicine
    Purpose: Today, male and female adult and pediatric cancer patients, individuals transitioning between gender identities, and other individuals facing health extending but fertility limiting treatments can look forward to a fertile future. This is, in part, due to the work of members associated with the Oncofertility Consortium. Methods: The Oncofertility Consortium is an international, interdisciplinary initiative originally designed to explore the urgent unmet need associated with the reproductive future of cancer survivors. As the strategies for fertility management were invented, developed or applied, the individuals for who the program offered hope, similarly expanded. As a community of practice, Consortium participants share information in an open and rapid manner to addresses the complex health care and quality-of-life issues of cancer, transgender and other patients. To ensure that the organization remains contemporary to the needs of the community, the field designed a fully inclusive mechanism for strategic planning and here present the findings of this process. Results: This interprofessional network of medical specialists, scientists, and scholars in the law, medical ethics, religious studies and other disciplines associated with human interventions, explore the relationships between health, disease, survivorship, treatment, gender and reproductive longevity. Conclusion: The goals are to continually integrate the best science in the service of the needs of patients and build a community of care that is ready for the challenges of the field in the future.