A Novel Discriminating Tool for Microcytic Anemia in Childhood.

Accurate and timely interpretation of microcytic anemia can be diagnostically challenging in the primary care setting. We sought to develop a novel model for distinguishing iron-deficiency anemia from thalassemia trait in the modern pediatric population. Demographic history and red blood cell indices were retrospectively characterized for 76 children referred to our pediatric hematology clinic for evaluation of microcytic anemia. Statistically significant variables were sequentially added into a logistic regression model to develop the final model. The final discriminating model incorporates red cell distribution width, mean corpuscular hemoglobin concentration, and red blood cell values. Favorable predictive performance is seen in the initial (sensitivity 89.2%, specificity 92.3%) and external validation cohort (sensitivity 84.4%, specificity 88.9%). This novel tool may aid in determining the cause of hypochromic, microcytic anemia in the primary care setting. Finally, the study cohort reflects an underrepresented group in the development of screening tools, and thus offers generalizability.

Social support experiences of hispanic/latino parents of childhood cancer survivors in a safety-net hospital: a qualitative study.

PURPOSE: To describe the social support experiences of Hispanic/Latino parents while caregiving for childhood cancer survivors. RESEARCH APPROACH: Semi-structured one-on-one interviews were conducted among 15 caregivers from a safety-net hospital in Los Angeles. A thematic analysis approach was used to analyze data. FINDINGS: The positive influence of social support throughout their caregiving experience included (1) sharing information-enhanced knowledge, (2) receiving comfort and encouragement, (3) receiving tangible assistance reducing the caregiving burden, and (4) enhancing caregiving empowerment/self-efficacy. Sub-themes regarding the lack of social support included (1) being a single parent and (2) family and friends withdrawing after the child's cancer diagnosis. CONCLUSION: We found Hispanic/Latino parents strongly value social support as it enables them to have essential resources that support caregiving for their child and themselves. Efforts should ensure that caregivers are routinely screened to identify their supportive needs so that support services for caregivers can be optimized and tailored, as those with a lack of social support may experience excessive caregiver burden.

Psychological Impact and Coping Strategies of Hispanic Parents of Children with Cancer: A Qualitative Study.

Throughout the cancer trajectory, parents of childhood cancer survivors (CCSs) may experience mental and social challenges requiring continual adaptation to cancer-induced stress. Using Lazarus and Folkman's Transactional Model of Stress and Coping framework, this qualitative study aimed to describe Hispanic parents' psychological health and explore their coping strategies. Purposive sampling was used to recruit 15 Hispanic caregivers from a safety-net hospital in Los Angeles County. To be eligible, participants had to be: the primary caregiver of a CCS who had completed active treatment, the primary caregiver or child self-identified as Hispanic, and proficient in English or Spanish. The interviews lasted approximately 60 min, were audio-recorded (in English and Spanish), and professionally transcribed. Data were analyzed following a thematic content analysis with deductive and inductive approaches on Dedoose. Participants described high levels of stress and fear when their child was diagnosed with cancer. They also shared experiencing symptoms of social anxiety, post-traumatic stress disorder, and depression. Participants' coping strategies were encompassed by three major themes: problem-focused, emotion-focused, and avoidant coping strategies. Problem-focused coping strategies included self-efficacy, behavioral change, and social support. Emotion-focused coping strategies included religious practices and positive reframing. Avoidant coping strategies included denial and self-distraction. Despite the evident disparities in psychological health for Hispanic parents of CCSs, gaps remain in designing a culturally tailored program to help alleviate the caregiver burden. This study provides insights regarding coping strategies that Hispanic caregivers use to deal with the psychological impact of their child's cancer diagnosis. Our findings also delve into the contextual and cultural factors that impact psychological adjustment.

Hispanic/Latinos and non-Hispanic whites' childhood cancer survivors and parents: a dyadic analysis of coping resources and mental health.

PURPOSE: While limited, dyadic research demonstrates the interdependent relationship between the health and adjustment after treatment between cancer survivors and caregivers. We examined interrelationships between coping resources and mental health among childhood cancer survivors (CCS)-parent dyads. METHODS: One hundred sixty CCS-parent dyads from the Project Forward pilot study completed validated questions assessing social support, religiosity, spirituality, depressive symptoms, and perceived stress. Bidirectional associations were identified with path analysis utilizing the actor-partner interdependence model (APIM). We used a multigroup approach to test for the moderating effects by Hispanic ethnicity on these relationships. RESULTS: Mean age of CCS was 20 years old, 51% female, 30% diagnosed with leukemia, and mean of 7 years from diagnosis. The mean age of parents was 49 years old and 89% were mothers. For both CCS and parents, perceived social support was inversely associated with their depressive symptoms and perceived stress (e.g., actor effects). Parents' social support was not significantly associated with CCS's depressive symptoms and stress. However, higher perceived social support by the CCS was inversely associated with parents' depressive symptoms (ß = - 0.202, p < 0.01) and perceived stress (ß = - 0.164, p < 0.05) (e.g., partner effects). Additional actor effects were observed between spirituality, religiosity, and depressive systems when we explored the moderating effects of Hispanic ethnicity. CONCLUSION: Partner effects of social support among CCS-parent dyads may influence psychological distress. IMPLICATION FOR CANCER SURVIVORS: Our findings on parent-child associations between social support and psychosocial well-being imply that survivorship care can be enhanced when the social support needs of both survivors and their parents are addressed together.

Barriers and facilitators of Hispanic/Latino parents caregiving for a childhood cancer survivor: a qualitative study.

PURPOSE: This qualitative study aimed to explore Hispanic parents of childhood cancer survivors (CCS) perceptions of facilitators and barriers to their caregiving experience. METHODS: We conducted semi-structured phone interviews with 15 Hispanic/Latino parents (English and Spanish). Parents were recruited using a purposive sampling method in a safety-net hospital in Los Angeles County from July-September 2020. Interviews were audio-recorded, professionally transcribed, and analyzed in the language they were conducted. Two coders independently coded interviews following reflexive thematic analysis and elements of grounded theory methodology. RESULTS: Most caregivers were mothers caring for leukemia CCS who had finished treatment more than 2 years prior. Caregivers expressed gratitude to social workers for introducing and aiding with the application process for safety-net programs that enabled caregivers to focus on their child's care and well-being. Caregivers revealed the importance of supportive communication with the medical team, particularly after their child's treatment was considered complete. All caregivers found caring for a child with cancer overwhelming, and many described deteriorations in their health and well-being. Financial instability, transportation difficulties, and work disruptions were identified as barriers, resulting in caregiver distress. Caregivers also shared the challenges they experienced navigating the healthcare system, seeking care despite lack of legal residency, and staying afloat despite limited employment opportunities. CONCLUSION: Improving navigation to resources and improving relationships with the medical team may reduce the perceived caregiving burden among Hispanic/Latino caregivers throughout their family's cancer journey.

Understanding Delayed Presentation to Emergency Care in Pediatric Patients With Neutropenic Fever.

We investigated social and logistic factors eg, distance from the medical center, language barriers, other children to care for, number of caregivers, etc.) for families to delay seeking immediate emergency care for neutropenic fever in a retrospective cohort study of all pediatric hematology-oncology patients who presented for fever in the setting of neutropenia to our emergency department or clinic from 2015 to 2020. Patients with a history of at least 2 prior admissions for neutropenic fever waited more often for a second fever before presenting versus those without such history (odds ratio 5.00, 95% CI 1.26 to 19.84, P =0.04). No other significant associations were found.

The Impact of Hispanic Ethnicity and Language on Communication Among Young Adult Childhood Cancer Survivors, Parents, and Medical Providers and Cancer-Related Follow-Up Care.

PURPOSE: The triad of communication between young adult childhood cancer survivors (YACCSs), their parents, and their medical providers is an important process in managing health care engagement. This study sought to identify communication patterns among this triad, factors associated with communication, and engagement of survivorship care. METHODS: We analyzed data from Project Forward, a population-based study that surveyed YACCSs and their parents. YACCSs were on average age 20 years, 7 years from diagnosis, 50% female, and 57% identified as Hispanic/Latino (N = 160 dyads). Latent class analysis of nine communication indicators from parent and YACCS surveys identified distinct classes of communication between YACCSs, parents, and medical providers. Associations between resulting classes and YACCS/parent characteristics were examined using multinomial logistic regression. Logistic regression was used to examine the association between communication classes and cancer-related follow-up care. RESULTS: Latent class analysis identified three classes of triad communication: (1) high health care-focused communication (37.5%), (2) high comprehensive communication (15.6%), and (3) overall low communication (46.9%). After adjusting for covariates, greater time since diagnosis was associated with reduced odds of membership in class 2 while dyads with Spanish-speaking Hispanic parents were more likely to be in class 2 (v class 3). Additionally, YACCSs who were in either of the high communication groups were more likely to have received recent follow-up care. CONCLUSION: Examining language preference provides an important contextual understanding as we found Spanish-speaking Hispanic parents engaged in high communication, which was associated with cancer-related follow-up care. Yet, our results also support the need to enhance communication between this triad to improve outcomes.

Survival of pediatric Hodgkin lymphoma patients treated with doxorubicin, bleomycin, vincristine, etoposide, prednisone, and cyclophosphamide (ABVE-PC) versus doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD) at a single institution.

BACKGROUND: Adriamycin, bleomycin, vinblastine, dacarbazine (ABVD), the de facto standard of care in adult-onset Hodgkin lymphoma (HL), has not been directly compared to doxorubicin, bleomycin, vincristine, etoposide, prednisone, and cyclophosphamide (ABVE-PC), a pediatric-aimed regimen designed to reduce late effects. We aimed to describe the single-institution experience of using both regimens in patients with pediatric HL. METHODS: This retrospective cohort study evaluated a total of 224 patients diagnosed with HL between 1999 and 2018 at Children's Hospital Los Angeles (CHLA), of which 93 patients were eligible having received ABVD (n = 46) or ABVE-PC (n = 47) chemotherapy as their initial treatment. Descriptive analyses were performed using the Student's t-test or Fisher's exact test. Survival analysis used the Kaplan-Meier method. Events included death, relapse, and secondary malignancy. We also describe the use of radiation therapy, pulmonary toxicity, and cardiomyopathy determined by shortening fraction <29%. Analyses followed an intention-to-treat principle. RESULTS: There was no difference in baseline characteristics between the patients receiving ABVE-PC or ABVD in regard for stage, risk group, or prognostic variables, such as the presence or absence of "B" symptoms, bulky disease, and extra-nodal involvement. A greater proportion of patients treated with ABVE-PC received consolidating external beam radiation treatment (XRT) either by randomization or by response compared to ABVD (59.6% vs. 32.6%, respectively, p = .01). While not statistically significant, response to therapy, assessed by positron emission tomography/computerized tomography (PET/CT) where available, mirrored the use for radiation (rapid response 58.3% vs. 90.0%, n = 34, p = .11). The median dose of anthracycline (doxorubicin) was the same in patients receiving ABVE-PC versus ABVD (200 vs. 200 mg/m2 , interquartile range 200-250 vs. 200-300 mg/m2 , p = .002). There was no difference in event-free survival (p = .63) or overall survival (p = .37) with a median follow-up length of 3.9 years. CONCLUSIONS: ABVD and ABVE-PC achieved similar survival outcomes in our single-institution cohort.

Effect of childhood obesity on admissions for respiratory disease.

AIM: The purpose of this study was to assess for an association between higher body mass index and disease severity, morbidity and mortality in children admitted for an acute respiratory distress and failure. METHODS: A single-institution retrospective cross-sectional study performed in the United States evaluating paediatric patients, 2-20 years of age, admitted for diagnoses related to acute respiratory distress and acute respiratory failure. Main outcomes include disease severity as assessed using the respiratory component of the Paediatric Early Warning Score (PEWS) with adjustment for altered mental status (Resp-PEWS + AMS), hospital or intensive care length of stay (LOS) and death. RESULTS: Children with obesity made up 42/334 (13%) of the cohort. There was no significant difference in Resp-PEWS + AMS between obese and non-obese cohorts (mean of 0.93, {standard deviation 1.11} vs. 1.13 {1.35}, range 0-6, rank sum p = 0.46). There was no significant difference in overall hospital LOS or intensive care LOS. Multivariate analysis including diagnosis as a control variable did not change the results. CONCLUSION: We found that body habitus was not an independent factor for illness severity or clinical outcomes.

Post-Chemotherapy Histiocyte-Rich Pseudotumors: Radiologic and Endoscopic Mimics of Residual Lymphoma.

Development of post-chemotherapy histiocyte-rich pseudotumor (PHP) is an underrecognized event following therapy in lymphoma patients and may mimic residual tumor using current therapy monitoring protocols. We report a series of 5 patients with PHP along with a review of the literature. In our series, we describe 3 patients with persistent hypermetabolic masses by positron emission tomography-computed tomography, one with persistent terminal ileal nodules on endoscopy, and one with bone marrow involvement, a site not associated with mass-like disease. Twenty-three patients with long-term follow-up were identified from our series and review of the literature. Forty-four percent of patients received additional therapy, and only 4% of patients died of lymphoma. This study illustrates that PHPs are not identified using current lymphoma therapy monitoring algorithms and may result in overtreatment with risk for additional therapy-related complications. The need for confirmatory tissue biopsy in this setting is recommended.

Combined immune checkpoint blockade increases CD8+CD28+PD-1+ effector T cells and provides a therapeutic strategy for patients with neuroblastoma.

Immune checkpoint therapy has resulted in minimal clinical response in many pediatric cancers. We sought to understand the influence of immune checkpoint inhibition using anti-PD-1 and anti-CTLA-4 antibodies individually, in combination, and after chemotherapy on immune responses in minimal and established murine neuroblastoma models. We also sought to understand the role of the tumor microenvironment (TME) and PD-L1 expression and their alteration post-chemotherapy in our models and human tissues. PD-L1 expression was enriched in human tumor-associated macrophages and up-regulated after chemotherapy. In a murine minimal disease model, single and dual immune checkpoint blockade promoted tumor rejection, improved survival, and established immune memory with long-term anti-tumor immunity against re-challenge. In an established tumor model, only dual immune checkpoint blockade showed efficacy. Interestingly, dual immune checkpoint therapy distinctly influenced adaptive and innate immune responses, with significant increase in CD8+CD28+PD-1+ T cells and inflammatory macrophages (CD11bhiCD11c-F4/80+Ly6Chi) in tumor-draining lymph nodes. Adding chemotherapy before immunotherapy provided significant survival benefit for mice with established tumors receiving anti-PD-1 or dual immune checkpoint blockade. Our findings demonstrate anti-PD-1 and anti-CTLA-4 therapy induces a novel subset of effector T cells, and support administration of induction chemotherapy immediately prior to immune checkpoint blockade in children with high-risk neuroblastoma.

Tumor-associated macrophages promote neuroblastoma via STAT3 phosphorylation and up-regulation of c-MYC.

Tumor-associated macrophages (TAMs) are strongly associated with poor survival in neuroblastomas that lack MYCN amplification. To study TAM action in neuroblastomas, we used a novel murine model of spontaneous neuroblastoma lacking MYCN amplification, and observed recruitment and polarization of TAMs, which in turn enhanced neuroblastoma proliferation and growth. In both murine and human neuroblastoma cells, we found that TAMs increased STAT3 activation in neuroblastoma cells and transcriptionally up-regulated the MYC oncogene. Analysis of human neuroblastoma tumor specimens revealed that MYC up-regulation correlates with markers of TAM infiltration. In an IL6ko neuroblastoma model, the absence of IL-6 protein had no effect on tumor development and prevented neither STAT3 activation nor MYC up-regulation. In contrast, inhibition of JAK-STAT activation using AZD1480 or the clinically admissible inhibitor ruxolitinib significantly reduced TAM-mediated growth of neuroblastomas implanted subcutaneously in NOD scid gamma mice. Our results point to a unique mechanism in which TAMs promote tumor cells that lack amplification of an oncogene common to the malignancy by up-regulating transcriptional expression of a distinct oncogene from the same gene family, and underscore the role of IL-6-independent activation of STAT3 in this mechanism. Amplification of MYCN or constitutive up-regulation of MYC protein is observed in approximately half of high-risk tumors; our findings indicate a novel role of TAMs as inducers of MYC expression in neuroblastomas lacking independent oncogene activation.