Male pediatric, adolescent, and young adult reproductive survivorship.

As pediatric, adolescent, and young adult cancer survival rates increase, emphasis is placed on reducing late effects, including reproductive complications and potential impact to fertility. Male survivors are at risk of abnormalities in sperm, hormone deficiencies, and sexual dysfunction. This can impact one's progression into puberty and ability to have a biological child and impacts quality of life following treatment. Access to reproductive care is important and requires patient assessment and appropriate referral to reproductive specialists. This review addresses reproductive complications associated with therapy, standard-of-care testing, and therapeutic interventions. The psychologic impact on psychosexual functioning is also addressed.

Composite Metric of Glycemic Control Q-Score Is Elevated in Pediatric and Adolescent/Young Adult Hematopoietic Stem Cell Transplant Recipients.

Background: Malglycemia in pediatric, adolescent and young adult (AYA) patients who undergo hematopoietic stem cell transplant (HSCT) is associated with increased infection and mortality rate. Continuous glucose monitoring (CGM) has been safely used in pediatric/AYA HSCT recipients, but there is a need for a composite metric that can easily be used in clinical settings to assess the glycemic control and identify high-risk patients who needs therapeutic intervention. Composite metrics derived from CGM have not been studied in pediatric/AYA HSCT patients. Methods: Patients aged 2-30 years old who are admitted inpatient while undergoing HSCT at Children's Hospital Colorado underwent CGM using the Abbot Freestyle Libre Pro device from up to 7 days before and 60 days after HSCT. A composite metric Q-score, comprising five primary factors of CGM profiles (central tendency, hyperglycemia, hypoglycemia, intradaily variations, and interdaily variations), was calculated for each patient for the duration of CGM wear. Results: Twenty-nine patients received CGM for an average of 25 days per participant. The median Q-score was 10.2 (interquartile range [IQR]: 8.3, 14.3). Sixty-nine percent of patients had Q-scores that would be categorized into the Fair or Poor category. There was no difference in the Q-score by sources of stem cell, types of primary disease, types of preparative regimen, need for PICU admission, presence of documented infections, and total parenteral nutrition use in the peri-HSCT period. Conclusions: Most pediatric/AYA HSCT recipients have Q-scores indicating suboptimal glycemic control in the peri-HSCT period. Future study should focus on developing screening and treatment strategies to improve malglycemia and its associated adverse clinical outcomes. This study was registered at clinicaltrials.gov (NCT03482154).

Psychosexual Care of Adolescent and Young Adult (AYA) Cancer Survivors.

Adolescent and young adult (AYA) survivors of cancer have diverse psychosocial and medical needs, including those related to fertility and sexual health. Much of the focus of care around issues such as fertility and sexual health tends to be filtered through a biomedical lens. However, it is essential that health care providers assess and support AYA survivors using a biopsychosocial and contextual framework to ensure the most comprehensive and accurate understanding of AYA survivor needs, especially those related to psychosexual health. A trusting relationship between the multi-disciplinary medical team and the AYA survivor that allows for open discussion about the physical and psychosocial components of sexual health is key to providing best care and outcomes.

Interventions to Improve Sexual Health in Women Living with and Surviving Cancer: Review and Recommendations.

Sexual health concerns, both physical and psychological, are common and represent an unmet need among women with and surviving cancer. Sexual challenges and conditions negatively impact body image, satisfaction, relationships, well-being, and quality of life, yet are widely reported to be under-recognized and undertreated. To guide clinical care and future research on sexual function in women with cancer, we performed a scoping review of interventions for sexual health concerns, including sexual function, body image, genitourinary symptoms, and hot flashes. Relevant publications between 2005 and 2020 were identified by searching PubMed with a combination of medical subject headings and keywords. Articles were included if they focused on the aforementioned topics, were primary research publications, and included female cancer survivors. Studies focusing on women receiving hormone therapy for breast cancer were also included. A total of 91 investigations conducted in the US and abroad were reviewed. Most commonly, interventions included a component of psychoeducation, although pharmacologic, exercise, and other approaches have been evaluated. Many studies have focused on survivors of breast or gynecologic cancer, among other sampling and methodological limitations. These limitations underscore the need for more work on this vital survivorship issue. Recommendations for future research in this area are also offered.

Adolescent and young adult childhood cancer survivors' preferences for screening and education of sexual function.

BACKGROUND: Sexual dysfunction (SD) is a common yet underrecognized concern among childhood cancer survivors (CCS). CCS who are now adolescent and young adult (AYA-CCS) identify SD as an unmet need. This study sought to explore AYA-CCS preferences on how, when, where, and by whom SD-focused communication should occur. PROCEDURE: This qualitative study utilized semi-structured interviews to explore AYA-CCS (now aged 15-24 years) experiences with, and preferences for, SD conversations. Thematic analysis methodology guided interpretation; themes were clustered into categories of who, how, when, and where SD conversations should occur. RESULTS: AYA-CCS highlighted the importance of patient-provider rapport to facilitate SD conversations, but did not have consistent preferences regarding provider type or specialty. Providers should reduce discomfort by normalizing ongoing, personalized conversations. Some AYA-CCS mentioned that notification that such a conversation is going to occur would be appreciated, and most were in favor of a screening tool to facilitate conversations. Preferences for when and where SD conversations should occur were centered on maximizing privacy. CONCLUSIONS: SD is an inadequately addressed concern in AYA-CCS, and providers must familiarize themselves with AYA-CCS preferences for discussing SD to reduce communication barriers and address this unmet need. In addition to corroborating prior studies' findings such as normalizing ongoing SD conversations, this study demonstrated novel ideas for reducing barriers, including use of a notification to prepare them prior to SD conversations, favoring the use of a screening tool, and the importance of establishing rapport prior to the SD conversations.

Circulating Plasma Tumor DNA Is Superior to Plasma Tumor RNA Detection in Ewing Sarcoma Patients: ptDNA and ptRNA in Ewing Sarcoma.

The detection of tumor-specific nucleic acids from blood increasingly is being used as a method of liquid biopsy and minimal residual disease detection. However, achieving high sensitivity and high specificity remains a challenge. Here, we perform a direct comparison of two droplet digital PCR (ddPCR)-based detection methods, circulating plasma tumor RNA and circulating plasma tumor DNA (ptDNA), in blood samples from newly diagnosed Ewing sarcoma patients. First, we developed three specific ddPCR-based assays to detect EWS-FLI1 or EWS-ERG fusion transcripts, which naturally showed superior sensitivity to DNA detection on in vitro control samples. Next, we identified the patient-specific EWS-FLI1 or EWS-ERG breakpoint from five patient tumor samples and designed ddPCR-based, patient-specific ptDNA assays for each patient. These patient-specific assays show that although plasma tumor RNA can be detected in select newly diagnosed patients, positive results are low and statistically unreliable compared with ptDNA assays, which reproducibly detect robust positive results across most patients. Furthermore, the unique disease biology of Ewing sarcoma enabled us to show that most cell-free RNA is not tumor-derived, although cell-free-DNA burden is affected strongly by tumor-derived DNA burden. Here, we conclude that, even with optimized highly sensitive and specific assays, tumor DNA detection is superior to RNA detection in Ewing sarcoma patients.

Provider Documentation of Tinnitus in Childhood Cancer Survivors.

Tinnitus is a known complication of treatment for childhood cancer and potentially reduces the quality of life for childhood cancer survivors (CCS). Although current guidelines recommend annual surveillance in CCS at risk for tinnitus, current screening practices among pediatric oncology survivorship providers are unknown. The authors performed a retrospective cohort study to assess the adequacy of current tinnitus screening in survivorship care. The 5.6% prevalence of tinnitus reported by the Childhood Cancer Survivorship Study, the largest ongoing follow-up cohort of CCS, served as the baseline for comparison for our rate of documented positive screening for tinnitus. Survivorship providers identified tinnitus in 3 of 624 (0.48%) eligible CCS, which was significantly lower than the prevalence in the Childhood Cancer Survivorship Study (P<0.0001). Survivorship providers documented any screening for tinnitus (positive or negative) in 15 of 624 (2.4%) CCS. Screening practices significantly differed by ototoxic exposure history and age at follow-up. This study demonstrates that screening and detection of tinnitus are underdocumented by survivorship providers, raising concern for inadequate screening practices. Improved screening may facilitate the recognition and treatment of this late effect, improving the quality of life for CCS.

Metastatic NUT Midline Carcinoma Treated With Aggressive Neoadjuvant Chemotherapy, Radiation, and Resection: A Case Report and Review of the Literature.

NUT midline carcinoma, characterized by the rearrangement of the nuclear protein in testis (NUTM1) gene, is a rare and aggressive subtype of squamous cell carcinoma. This disease is rarely cured and there have been no reports of cure in patients with distant metastatic disease. In fact, patients typically succumb to NUT midline carcinoma within 6 to 12 months from diagnosis. The authors report on a single patient who presented widely metastatic disease who has now been in remission for 37 months after multimodal therapy with compressed cycles of vincristine, cyclophosphamide, and doxorubicin alternating with ifosfamide and etoposide, high-dose radiation, and postchemotherapy resection.

Evaluation of the v2.0 Brief Profiles for Sexual Function and Satisfaction PROMIS in Adolescent and Young Adult Childhood Cancer Survivors.

Purpose: Sexual dysfunction (SD) is a common, but often unrecognized potential late effect among childhood cancer survivors (CCS). Unfortunately, both patients and providers report low levels of routine screening and identify multiple barriers, including lack of knowledge, discomfort, and limited time. This is particularly true among CCS who are adolescent or young adult aged (AYA-CCS). One potential way to increase screening, detection, and treatment for SD among AYA-CCS is to employ patient-reported outcomes measures. While adult screening tools exist, no SD screening tool has been evaluated specifically among this younger population. Methods: This qualitative study used Think-Aloud and cognitive interviewing methods to obtain feedback from AYA-CCS on acceptability, usefulness, and validity of the Patient-Reported Outcomes Measurement Information System® (PROMIS®) v2.0 Brief Profiles for Sexual Function and Satisfaction (SexFS Brief) in CCS now 15-24 years of age. Results: The SexFS Brief demonstrated acceptability, response process and content validity, and usefulness among AYA-CCS. There were no detectable differences by age or gender. This study did not reveal any necessary modification to the SexFS Brief for this population. Conclusion: The PROMIS SexFS Brief is an acceptable and useful tool, with demonstrated response process and content validity, and may facilitate improved screening and diagnosis of SD among AYA-CCS. Furthermore, this tool was viewed favorably by AYA-CCS as a way to reduce barriers such as discomfort and lack of knowledge on the part of patients. Further evaluation of its effectiveness and acceptability in a clinical setting is warranted.

Sexual Dysfunction in Adolescent and Young Adult Survivors of Childhood Cancer: Presentation, Risk Factors, and Evaluation of an Underdiagnosed Late Effect: A Narrative Review.

An area of concern affecting the quality of life of childhood cancer survivors (CCS) is that of sexual dysfunction (SD), which may be a result of both physical and psychosexual challenges associated with cancer and its treatment. This is especially pertinent as CCS are known to experience diminished quality of life compared to peers. Relevant to SD, cancer and its associated treatment are associated with negative effects on body image and romantic relationships, as well as overall physical and mental health. Although CCS have been shown to have SD at higher rates than the general population, this is often under-recognized and CCS commonly report that it is not addressed by their health care providers. To guide future research and improve clinical screening and treatment practices for SD, we performed a narrative review of this understudied topic to summarize existing knowledge of the incidence, risk factors, pathophysiology, and rates of screening for SD in CCS. We also outline current gaps in knowledge and directions for future research.

Safety and Accuracy of Factory-Calibrated Continuous Glucose Monitoring in Pediatric Patients Undergoing Hematopoietic Stem Cell Transplantation.

Background: Pediatric patients undergoing hematopoietic stem cell transplantation (HSCT) may be at risk for malglycemia and adverse outcomes, including infection, prolonged hospital stays, organ dysfunction, graft-versus-host-disease, delayed hematopoietic recovery, and increased mortality. Continuous glucose monitoring (CGM) may aid in describing and treating malglycemia in this population. However, no studies have demonstrated safety, tolerability, or accuracy of CGM in this uniquely immunocompromised population. Materials and Methods: A prospective observational study was conducted, using the Abbott Freestyle Libre Pro, in patients aged 2-30 undergoing HSCT at Children's Hospital Colorado to evaluate continuous glycemia in this population. CGM occurred up to 7 days before and 60 days after HSCT, during hospitalization only. In a secondary analysis of this data, blood glucoses collected during routine HSCT care were compared with CGM values to evaluate accuracy. Adverse events and patient refusal to wear CGM device were monitored to assess safety and tolerability. Results: Participants (n = 29; median age 13.1 years, [interquartile range] [4.7, 16.6] years) wore 84 sensors for an average of 25 [21.5, 30.0] days per participant. Paired serum-sensor values (n = 893) demonstrated a mean absolute relative difference of 20% ± 14% with Clarke Error Grid analysis showing 99% of pairs in the clinically acceptable Zones (A+B). There were four episodes of self-limited bleeding (4.8% of sensors); no other adverse events occurred. Six patients (20.7%) refused subsequent CGM placements. Conclusions: CGM use appears safe and feasible although with suboptimal accuracy in the hospitalized pediatric HSCT population. Few adverse events occurred, all of which were low grade.

Glycemic variability is associated with poor outcomes in pediatric hematopoietic stem cell transplant patients.

BACKGROUND: Among pediatric hematopoietic stem cell transplant (HSCT) recipients, abnormal glycemic control is shown to be associated with increased risk of transplant-related mortality, death from any cause, risk of infection, increased hospitalized, and intensive care days. Independent effects of higher glycemic variability, a component of glycemic control, have not been described. This study aimed to characterize risk factors for, and consequences of, higher glycemic variability in HSCT patients. PROCEDURE: Medical records for a cohort of 344 patients, age 0-30 years, who underwent first HSCT from 2007 to 2016 at Children's Hospital Colorado were retrospectively reviewed. Glucose coefficients of variation (CV) were analyzed for HSCT days -14 to 0 and 0-30, and patients were assessed for potential risk factors and outcomes. RESULTS: Roughly one-third of patients had pre-HSCT and day 0-30 glucose CV above the reported healthy adult range. Independent of HSCT type, doubling of pre-HSCT glucose CV was associated with a 4.91-fold (95% confidence interval [CI], 1.40-17.24) increased hazard of infection, as well as increased risk for intensive care hospitalization for allogenic HSCT patients. Multivariable analysis demonstrated that allogeneic HSCT patients had a 1.40- and 1.38-fold (95% CI, 0.98-1.99 and 1.00-1.91) increased hazard of death for every doubling of pre-HSCT and day 0-30 glucose CV, respectively. CONCLUSIONS: Just as with higher mean glucose, higher glycemic variability in the pediatric HSCT population is independently associated with significantly increased morbidity. Additional research is required to evaluate the utility of glucose control to mitigate these relationships and improve HSCT outcomes.

Hyperglycemia During Childhood Cancer Therapy: Incidence, Implications, and Impact on Outcomes.

Hyperglycemia is a known complication of therapies used in the treatment of childhood cancer, particularly glucocorticoids and asparaginase. It has been linked to increased infection and reduced survival. With more limited data on hyperglycemia during childhood cancer treatment compared with adult cancer, impact on outcomes is less clear in this population. As additional glycemic-altering cancer agents including immune checkpoint inhibitors and targeted therapies make their way into pediatric cancer treatment, there is a more pressing need to better understand the mechanisms, risk factors, and adverse effects of hyperglycemia on the child with cancer. Thus, we utilized a systematic approach to review the current understanding of the incidence, implications, and outcomes of hyperglycemia during childhood cancer therapy.

Development and evaluation of a computable phenotype to identify pediatric patients with leukemia and lymphoma treated with chemotherapy using electronic health record data.

BACKGROUND: Widespread implementation of electronic health records (EHR) has created new opportunities for pediatric oncology observational research. Little attention has been given to using EHR data to identify patients with pediatric hematologic malignancies. METHODS: This study used EHR-derived data in a pediatric clinical data research network, PEDSnet, to develop and evaluate a computable phenotype algorithm to identify pediatric patients with leukemia and lymphoma who received treatment with chemotherapy. To guide early development, multiple computable phenotype-defined cohorts were compared to one institution's tumor registry. The most promising algorithm was chosen for formal evaluation and consisted of at least two leukemia/lymphoma diagnoses (Systematized Nomenclature of Medicine codes) within a 90-day period, two chemotherapy exposures, and three hematology-oncology provider encounters. During evaluation, the computable phenotype was executed against EHR data from 2011 to 2016 at three large institutions. Classification accuracy was assessed by masked medical record review with phenotype-identified patients compared to a control group with at least three hematology-oncology encounters. RESULTS: The computable phenotype had sensitivity of 100% (confidence interval [CI] 99%, 100%), specificity of 99% (CI 99%, 100%), positive predictive value (PPV) and negative predictive value (NPV) of 100%, and C-statistic of 1 at the development institution. The computable phenotype performance was similar at the two test institutions with sensitivity of 100% (CI 99%, 100%), specificity of 99% (CI 99%, 100%), PPV of 96%, NPV of 100%, and C-statistic of 0.99. CONCLUSION: The EHR-based computable phenotype is an accurate cohort identification tool for pediatric patients with leukemia and lymphoma who have been treated with chemotherapy and is ready for use in clinical studies.

Malglycemia is associated with poor outcomes in pediatric and adolescent hematopoietic stem cell transplant patients.

Malglycemia (hypoglycemia, hyperglycemia, and/or glycemic variability) in adult hematopoietic stem cell transplant (HSCT) recipients is associated with increased infection, graft-versus-host disease, organ dysfunction, delayed engraftment, and mortality. Malglycemia has not been studied in pediatric HSCT recipients. This study aimed to characterize the incidence and consequences of malglycemia in this population. Medical records for a cohort of 344 patients, age 0 to 30 years, who underwent first HSCT from 2007 to 2016 at Children's Hospital Colorado were retrospectively reviewed. Glucose data were analyzed in intervals and assessed for potential risk factors and associated outcomes. Malglycemia occurred in 43.9% of patients. Patients with a day 0 to 100 mean glucose of 100 to 124 mg/dL had a 1.76-fold (95% confidence interval [CI], 1.10-2.82; P = .02) increased risk of death and patients with a day 0 to 100 mean glucose ≥ 125 mg/dL had a 7.06-fold (95% CI, 3.84-12.99; P < .0001) increased risk of death compared with patients with a day 0 to 100 mean glucose < 100 mg/dL. For each 10 mg/dL increase in pre-HSCT glucose, there was a 1.11-fold (95% CI, 1.04-1.18; P = .0013) increased risk of post-HSCT infection. These adverse impacts of malglycemia occurred independent of transplant type, graft-versus-host disease, and steroid therapy. Malglycemia in the pediatric HSCT population is independently associated with significantly increased risk of morbidity and mortality. Further research is required to evaluate the utility of glucose control to mitigate these relationships and improve HSCT outcomes. This trial was registered at www.clinicaltrials.gov as #NCT03482154.

Castleman disease in pediatrics: Insights on presentation, treatment, and outcomes from a two-site retrospective cohort study.

BACKGROUND: Castleman disease (CD) is an uncommon lymphoproliferative disorder that is rare in pediatric populations; the literature describing this population is sparse. We sought to describe pediatric CD, including unicentric CD (UCD) and human herpes virus-8 (HHV8)-negative multicentric CD (MCD), in a multi-institutional cohort. METHODS: We retrospectively reviewed 24 patients, aged 0 to 26 years at diagnosis, who were diagnosed with CD between January 1, 2005, and May 16, 2017, at two tertiary children's hospitals. Demographic and clinical data were collected. RESULTS: Most patients (75%, 18/24) presented with UCD. All patients with MCD were HHV8-negative. The most common histopathologic variant was hyaline vascular (75%, 18/24). Plasma cell variant occurred in 33% (2/6 [95% confidence intervals (CI), 4-78%]) of patients with HHV8-negative MCD and 17% (3/18 [95% CI, 4-41%]) of patients with UCD. Systemic symptoms were present in 4 of 6 of patients with HHV8-negative MCD and 8 of 18 of patients with UCD. Anemia and laboratory inflammation occurred in both UCD and MCD patients, with nonsignificantly higher rates of anemia and elevated C-reactive protein in MCD patients. All but two UCD patients underwent gross total resection as definitive therapy. Among HHV8-negative MCD patients, a combination of resection, chemotherapy, and immunotherapy was used. No UCD patients and three of six HHV8-negative MCD patients experienced disease progression/relapse prior to lasting remission. There were no deaths. CONCLUSION: Pediatric patients with CD most commonly have unicentric, hyaline vascular variant disease. Pediatric patients with both UCD and MCD commonly have systemic inflammation and, despite risk of progression/relapse in MCD patients, ultimately have excellent survival.

Pulmonary toxicity in paediatric patients with relapsed or refractory Hodgkin lymphoma receiving brentuximab vedotin.

Brentuximab vedotin (Bv) is becoming increasingly important in the treatment of Hodgkin lymphoma (HL), with improved outcomes and an overall favourable toxicity profile. However, Bv is associated with severe pulmonary toxicity when combined with bleomycin, suggesting that additive toxicity may be an important consideration. Furthermore, little has been published on tolerability in paediatric patients. We retrospectively evaluated the occurrence of pulmonary toxicity of Bv in 19 paediatric and young adult patients with relapsed or refractory HL. Patient characteristics, baseline health status, treatment regimens including cumulative doses of Bv, bleomycin, gemcitabine, radiation and carmustine, and the occurrence of pulmonary toxicity were collected. Seven (36·8%) of the 19 patients were treated with Bv. The odds of pulmonary toxicity were 4·0-fold higher (95% confidence interval 0·55-29·18) in patients exposed to Bv compared to unexposed patients in univariate analysis (P = 0·17). Similar results were found in multivariable analysis. Pulmonary toxicity occurred frequently in our cohort and was more common in patients who received Bv than in patients who did not receive Bv, although this was not statistically significant. Because patients with HL are exposed to a myriad of therapies with potential for pulmonary toxicity, continuing to evaluate the risk associated with Bv is critical.

Positive Impact of Transition From Noon Conference to Academic Half Day in a Pediatric Residency Program.

OBJECTIVE: To evaluate the impact of transitioning from noon conference (NC) to academic half day (AHD) on conference attendance, interruptions, and perceived protected educational time and to describe pediatric resident experiences with AHD. METHODS: In this mixed-methods study, data before and after AHD implementation were collected. Quantitative data were analyzed with a 2-variable t test or chi-square test. Five focus groups and 5 individual interviews of pediatric residents were conducted. Data were analyzed using constant comparative methods, and were collected until reaching saturation. In accordance with grounded theory methodology, we developed codes using an iterative approach and identified major themes. RESULTS: After AHD implementation, resident attendance increased from 55% (of residents expected at NC) to 94% (of residents scheduled for AHD) (P < .001); interruptions decreased from 0.25 to 0.01 per resident per hour (P < .001). Positive responses regarding perceived protected educational time improved from 50% to 95% (2015 class) and from 19% to 50% (2016 class) (P < .001). Thirty-two residents participated in focus groups and interviews. Analysis yielded 5 themes: aids and barriers to AHD attendance; teaching; curricular content; learning and engagement; and resident well-being. Residents felt aided attending AHD when clinical supervisors supported their educational time. Compared to NC, residents noted better topic selection but fewer covered topics. Residents valued protected educational time without clinical responsibilities and thought that small-group discussions at AHD facilitated learning. Although cross-covering was stressful, AHD positively contributed to resident well-being. CONCLUSIONS: AHD improves resident attendance, interruptions, and perceived learning, and it contributes to resident wellness. More work is needed to mitigate the workload of cross-covering residents.

Screening for vitamin D insufficiency in pediatric cancer survivors.

BACKGROUND: Corticosteroids increase risk for decreased bone mineral density, which can be worsened by vitamin D insufficiency (VDI) or deficiency (VDD). PROCEDURE: In the Vanderbilt cancer survivorship clinic, we obtained screening total 25-hydroxy vitamin D levels (VDL) in 171 cancer survivors <23 years old who were treated with prolonged corticosteroids for their cancer, and compared this group to a control group of 97 healthy pediatric patients. RESULTS: VDD was diagnosed in 15.8% and VDI in 34.5% of cancer survivors and VDD/VDI combined was associated with body mass index (BMI) >85th percentile (Odds ratio [OR] = 5.4; P < 0.001), older age (OR = 2.2; P = 0.012), non-Caucasian or Hispanic race (OR = 4.5; P = 0.008) and summer versus winter season (OR = 0.12; P < 0.001). In multivariable analysis, VDI/VDD prevalence did not differ from the control group (VDI/VDD (43.3%)). In the combined survivor/control group multivariable analysis, cancer diagnosis did not increase VDI/VDD risk, but significant associations persisted with elevated BMI (P < 0.001), age (P = 0.004), non-Caucasian or Hispanic race (P < 0.001), and seasonality (P < 0.001). CONCLUSION: VDD/VDI is equally common in pediatric cancer survivors treated with corticosteroids and healthy children. The impact of VDD/VDI in cancer survivors may be greater due to risk for impaired bone health superimposed on that conferred from corticosteroid exposure. Thus, screening VDLs should be obtained in pediatric cancer survivors treated with corticosteroids, particularly in those with elevated BMI, older age, or non-Caucasian race. Prospective studies evaluating the impact of interventions to minimize VDD/VDI on long-term bone health in survivors are required.

Failure to thrive, hyponatremia, and hyperkalemia in a neonate.

CME EDUCATIONAL OBJECTIVES: 1.Describe the varying clinical presentations of pseudohypoaldosteronism in the neonatal period.2.Review the physiology of aldosterone production and pathophysiology of pseudohypoaldosteronism.3.Identify treatment options for pseudohypoaldosteronism when identified in the neonatal period. Pseudohypoaldosteronism type I (PHA1) is a rare disease of mineralocorticoid resistance caused by defects in sodium transport in the distal tubule of the kidney. It presents in the neonate with life-threatening dehydration due to salt wasting, accompanied by hyperkalemia, acidosis, and, frequently, failure to thrive. Patients with PHA1 are often initially diagnosed with congenital adrenal hyperplasia, but their electrolyte abnormalities are resistant to treatment with glucocorticoids and mineralocorticoids. In these patients, an astute clinician will broaden his or her differential, resulting in life-saving treatment.