Children's Hospital Los Angeles Research Articles

Impact of Central Nervous System (CNS) Leukemia Status-Based Therapeutic Protocol Change on the Incidence of CNS2 Diagnosis in Pediatric B-Lymphoblastic Acute Leukemia

B-lymphoblastic acute leukemia (B-ALL) is the most prevalent cancer among children, and prophylactic central nervous system (CNS) therapy has significantly contributed to high cure rates for the past 50 years. However, relapses in bone marrow and/or CNS continue to pose challenges to achieving cure for all patients, especially in those with high-risk disease. CNS status at diagnosis, defined as CNS1 (no blasts present), CNS2 (blasts with <5 total white blood cells [WBC] per mm 3 in a cerebrospinal fluid [CSF] sample), and CNS3 (blasts with ≥5 total WBC per mm 3 or grossly traumatic), plays a crucial role in determining treatment stratification. In the past, patients with CNS1 and CNS2 received similar therapy, but evidence suggested that those with CNS2 were at a higher risk for marrow and/or CNS relapse. As a result, the Children's Oncology Group (COG) frontline trials AALL1131 and AALL0932 implemented additional CNS therapy for CNS2 patients beginning in 2012 and 2016, respectively, specifically twice weekly intrathecal chemotherapy until CSF cleared of disease 3 consecutive times. This change highlighted the necessity for accurate identification of CNS2. Based on anecdotal observation, we hypothesized that the incidence of CNS2 among pediatric B-ALL patients at diagnosis was higher after this therapeutic change due to pathologist awareness of its implications for patient management. The electronic medical records of all consecutive pediatric patients diagnosed with B-ALL at Children's Hospital Los Angeles (CHLA) from September 2008 to December 2019 were reviewed. CSF WBC count and blast involvement were used to calculate CNS status. Blast involvement was determined by one or more pathologists per case by morphologic review of cytocentrifuged CSF material. The patients were divided into two cohorts, one before (cohort A) and one after (cohort B) the COG AALL0932 protocol change (May 20, 2016). Differences between cohorts were evaluated via Fisher's exact test and Wilcoxon rank sum test. All tests were two-sided, except for CNS2 status, and significance level was set a priori at 0.05. During the study period, 391 patients were diagnosed with B-ALL at CHLA. These included 192 patients prior to the CNS status-based therapeutic change (cohort A) and 199 patients after the therapeutic change (cohort B). The incidence of CNS2 status was higher in cohort B (20%) than in cohort A (13%) (p=0.052). Conversely, the incidence of CNS1 status was lower in cohort B (77%) than in cohort A (85%), while the incidence of CNS3 was similar before (5%) and after (4%) the protocol change. There were no differences between the cohorts in patient age at diagnosis [cohort A: mean age 8.91 years (SD 5.67 years) vs. cohort B: mean age 8.10 (SD 5.62 years); p=0.20], sex (cohort A: 59.9% male vs. cohort B: 58.8% male; p=0.80), or ethnicity (cohort A: 76.0% Hispanic vs. cohort B: 67.7% Hispanic; p=0.09). These data suggest that the incidence of CNS2 status in pediatric patients with B-ALL at our institution was higher after (20%) than before (13%) the COG protocol changes that began treating CNS2 patients more intensively than CNS1 patients. In addition to increased frequency of intrathecal chemotherapy, in the ongoing frontline COG standard-risk ALL trial, patients with CNS2 status and neutral cytogenetics are upstaged to higher-risk therapy irrespective of end-induction response. A limitation of this study is that pathologist reviewers of CSF cytospin morphology at the time of CNS assignment differed during the two time periods, such that an observational bias cannot be entirely excluded. Notably, flow cytometry - a more sensitive methodology than cytospin morphology for detection of leukemic cells in CSF material - was not used in these cohorts, but increasingly widespread adoption of such techniques may further increase the incidence of CNS2, including in patients who would otherwise have been diagnosed with CNS1 disease (by cytospin morphology) and as such may be overtreated. Future directions of our study include examination of clinical outcome as well as recent (2021-present) patterns of flow cytometry use in CSF specimens and associated diagnoses of CNS disease in pediatric patients with B-ALL at diagnosis.

Optical Genome Mapping Allows Detection and Characterization of Cytogenetically Cryptic Oncogenic Fusions in Pediatric Acute Myeloid Leukemia

Background: Abnormal gene fusions are predominant oncogenic drivers in pediatric acute myeloid leukemia (AML) and are important diagnostic and prognostic markers. However, several oncogenic fusions specific for or enriched in pediatric AML (like CBFA2T3::GLIS2, NUP98::NSD1, ETV6::MNX1 and others) are not detectable by conventional cytogenetic analysis (cytogenetically cryptic) and may not be included in fluorescence in situ hybridization (FISH) or molecular fusion panels designed for adult patients. Optical genome mapping (OGM) is a powerful new method for genome-wide, high-resolution detection of copy number abnormalities and balanced chromosome rearrangements. This study determined the frequency of cryptic oncogenic fusions in an institutional cohort of pediatric AML cases and evaluated OGM as a method for their detection and characterization. Methods: Retrospective review of genetic testing results was performed for 93 consecutive de novo or relapsed pediatric AML cases tested at the Children's Hospital Los Angeles (CHLA) Center for Personalized Medicine between March 2016 and July 2023. Genetic testing was performed as part of clinical care following standard procedures and consisted of karyotype analysis, FISH testing, chromosomal microarray (CMA) analysis, CHLA custom sequencing panel (OncoKids®) (June 2017 onwards) and RNA-Seq fusion assay (March 2022 onwards). Cases with normal or inconclusive karyotype in which an oncogenic fusion was detected by another clinical assay were selected for OGM testing. High molecular weight DNA from peripheral blood or bone marrow samples was labeled, processed and imaged in a Saphyr System and analyzed in the Bionano Access software following the manufacturer's recommendations (BionanoGenomics, San Diego CA). Results: Out of 93 pediatric AML cases included in the study, a gene fusion was identified as the primary oncogenic driver in 54 (58%) and a DNA sequence variant in 11 (12%). In 28 cases (30%), the primary genetic abnormality remained undetermined after comprehensive genetic testing. In 17/54 (31%) fusion-driven cases [17/93 (18%) overall cases], the oncogenic fusion remained undetected by karyotype analysis (cryptic). OGM was completed in 13/17 fusion positive cases with non-informative karyotype; it could not be performed in 4 cases due to lack of samples (n=2) or poor DNA quality (n=2), and is still in progress for a subset of 28 unknown cases with available material. OGM analysis successfully revealed all cryptic fusions previously detected by FISH, CMA, OncoKids® and/or RNA-Seq, including NUP98::NSD1 (n=3), KMT2A::MLLT10 (n=3), KMT2A::MLLT3 (n=2)and one case each of CBFA2T3::GLIS2, NUP98::KDM5A, DEK::NUP214, MYB::GATA1 and ETV6::MNX1. Chromosomal mechanism and structure of cryptic fusions were resolved by OGM and included: intrinsically cryptic fusions due to chromosome location of partner genes ( NUP98::NSD1, n=4; CBFA2T3::GLIS2, NUP98::KDM5A and ETV6::MNX1, n=1 each); complex rearrangements due to incompatible gene orientation ( KMT2A::MLLT10 n=2; MYB::GATA1, n=1); three-way rearrangements involving an additional chromosome ( KMT2A::MLLT3 n=2) and small insertions ( KMT2A::MLLT10 and DEK::NUP214, n=1 each). OGM also matched the performance of chromosomal microarray (CMA) analysis in detection of copy number variants. Conclusions: We confirm the significant contribution of cryptic chromosome rearrangements to pathogenesis of pediatric AML, and highlight the importance of tailored testing approaches that effectively detect highly heterogeneous fusion drivers. Our preliminary results show potential of OGM to identify clinically significant cryptic fusions in pediatric AML, and to thus markedly increase diagnostic yield compared to karyotype analysis. As a single assay that detects abnormalities currently interrogated by conventional cytogenetics, FISH and CMA, OGM may allow streamlined and more cost-effective genetic evaluation for pediatric AML.

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.

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. 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. 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. 200mg/m2 , interquartile range 200-250 vs. 200-300mg/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 3.9years. ABVD and ABVE-PC achieved similar survival outcomes in our single-institution cohort.

Histrelin Implants for Suppression of Puberty in Youth with Gender Dysphoria: A Comparison of 50 mcg/Day (Vantas) and 65 mcg/Day (SupprelinLA).

Purpose: Development of incongruent secondary sex characteristics in transgender youth can intensify or trigger the onset of gender dysphoria. Guidelines from professional organizations recommend gonadotropin-releasing hormone agonists, including histrelin implants (Vantas and SupprelinLA) to suppress endogenous puberty. Although Vantas does not have a pediatric indication, it is anecdotally being used in pediatric gender centers throughout the United States because of its substantially lower cost. This retrospective study aimed to determine if both implants were effective in suppressing the hypothalamic–pituitary–gonadal axis in early-to-mid pubertal youth with gender dysphoria.Methods: Youth with gender dysphoria receiving care at the Center for Transyouth Health and Development at Children's Hospital Los Angeles (CHLA) or participants from an ongoing observational trial with a histrelin implant placed for pubertal suppression at Tanner stage 2 or 3 were included. Sex steroid (testosterone or estradiol) and gonadotropin measurements at baseline (T0) and then 2 to 12 months following implant placement (T1) were abstracted from medical records.Results: Of the 66 eligible participants, 52% were designated female at birth. Most participants were white (60.6%). Twenty participants (30.3%) had a Vantas implant and 46 (69.7%) had a SupprelinLA implant. Mean age of insertion was 11.3 years. Gonadotropin and sex steroid levels were significantly decreased at T1 (2–12 months after insertion of implant), with no differences between implants.Conclusion: These results indicate that both implants are effective in suppressing puberty in early-to-mid pubertal youth with gender dysphoria. These data may inform decisions about insurance coverage of Supprelin and/or Vantas for youth with gender dysphoria.

Abstract A013: Parental health communication and satisfaction with medical providers of childhood cancer survivors: Differences by race/ethnicity and language

Abstract Purpose: Among childhood cancer survivors (CCS), parents inherently take on the role of informal caregivers. Effective communication between patient and provider or caregiver contributes to better treatment decision making and patient health outcomes. However, few studies have examined the frequency and scope of communication among childhood cancer survivors, caregivers, and medical providers. The purpose of this study was to examine the association between Hispanic ethnicity and language spoken with communication and satisfaction with their CCS health care provider. We hypothesized that Spanish-speaking Hispanic parents would have more barriers with provider communication and would be less satisfied with medical providers than English-speaking Hispanics and non-Hispanic parents. We also hypothesized that Spanish-speaking Hispanic parents would have greater communication with their child about their diagnosis. Methods: We analyzed data from parents of CCS, who were selected from the Los Angeles Cancer Surveillance Program and had been diagnosed between 2000 and 2007 at Children's Hospital Los Angeles (CHLA) or Miller Children's Hospital, Long Beach. We used ANOVA and chi-square statistics to test for differences in demographic characteristics. Results: A total of 173 parents participated in this study, including 50 Spanish-speaking Hispanics, 49 English-speaking Hispanics, and 74 English-speaking non-Hispanics. Spanish-speaking Hispanics were younger, had less than high school education, were lower income, and were less likely to have health care coverage compared to English-speaking Hispanics and non-Hispanic parents. Spanish-speaking Hispanic parents were more likely to report talking to their child about his/her needs for cancer-related follow-up care (p&amp;lt;.001) and health insurance issues (p=.01). Regardless of language spoken, Hispanic parents were more likely to receive health information about their child's cancer from hospital sources. Spanish-speaking Hispanic parents were more likely than English-speaking Hispanics and non-Hispanic parents to report difficulties with written information (p=.02) and understanding doctors due to language barriers (p=.003). However, there was no statistically significant difference by ethnicity/language in parent satisfaction with their child's health care provider or in receiving a survivorship care plan. Conclusion: Despite reporting similar rates of satisfaction with CCS medical providers, Spanish-speaking parents were more likely to report communication barriers with providers. Nevertheless, in order to build sustainable relationships with providers, language barriers need to be addressed to improve communication effectiveness. In future studies, we will explore the role of parent-child and parent-provider communication on their health outcomes. Citation Format: Carol Y. Ochoa, Lourdes Baezconde-Garbanati, Joel Milam. Parental health communication and satisfaction with medical providers of childhood cancer survivors: Differences by race/ethnicity and language [abstract]. In: Proceedings of the Eleventh AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2018 Nov 2-5; New Orleans, LA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2020;29(6 Suppl):Abstract nr A013.

Autoimmune Gastritis in Pediatrics: A Review of 3 Cases.

To bring heightened awareness to a condition, autoimmune gastritis (AIG), which is a well-established entity in adults; however, rarely described in pediatrics. Currently, the literature describes AIG in pediatric patients who also suffer from other autoimmune disorders, which precedes the diagnosis of AIG, and often presents with unexplained anemia. Additionally, there have been case reports describing patients with immunodeficiencies and AIG, which progress to gastric adenocarcinoma. AIG is a histopathologic diagnosis, demonstrating chronic inflammatory process with loss of parietal cells with or without intestinal metaplasia and enterochromaffin-like cell hyperplasia. Management of these patients includes nutritional replacement as well as routine surveillance endoscopy with biopsy in search of metaplastic and dysplastic changes. We queried the pathology database at Children's Hospital Los Angeles (CHLA) for cases with a final diagnosis of AIG and for those with a differential diagnosis that includes AIG in the diagnostic comment. All cases that were identified were selected as long as they did not only meet the histopathologic criteria, but also the biochemical criteria for this condition. Of the 3 patients, 2 were referred to gastroenterology for the evaluation of iron-deficiency anemia in the context of diabetes mellitus and Addison's disease; and diabetes mellitus and Hashimoto's thyroiditis. AIG was confirmed on the biopsies, which showed a reduction in parietal cell mass, pseudopyloric metaplasia and enterochromafin-like cell hyperplasia. Both patients were treated with iron replacement therapy. The third patient presented with symptomatic anemia and diagnosed with pernicious anemia without other autoimmune disorders. She was successfully treated with oral vitamin supplementation. In this case, serial gastric biopsies demonstrated stable intestinal metaplasia without evidence of dysplasia. Although AIG is rare in children, pediatric gastroenterologists and pathologists should have a heightened suspicion for this entity in those patients with a history of autoimmune disorders and/or pernicious anemia.

DOZ047.70: Prevalence of abnormal triple endoscopy findings for tracheoesophageal fistula patients in a multidisciplinary aerodigestive clinic

Abstract Introduction Tracheoesophageal fistula (TEF) is a rare congenital defect involving malformations of the esophagus and trachea, which can be life-threatening if left untreated. Children who have undergone TEF repair often present with symptoms such as cough, vomiting, and growth failure. Although the variety of these symptoms implies a necessity for a multidisciplinary approach to care of TEF repair patients, many are still followed by a single discipline such as gastroenterology or pulmonology. The purpose of this study is to describe the experience of Children's Hospital Los Angeles Aerodigestive team in evaluating TEF patients using an interdisciplinary approach. In particular, we aim to explore the findings obtained during triple endoscopy in order to confirm the necessity of care by multiple specialties, ideally in the setting of an Aerodigestive Clinic. Methods Consent was obtained for all children (birth to 18 years) seen in the Children's Hospital Los Angeles (CHLA) Aerodigestive (AERO) Clinic between June 2016 and August 2018. All patients with a diagnosis of TEF were included in the study and data collected included: age, sex, presenting diagnoses and symptoms, and triple endoscopy findings. Results Of the first 109 patients in the AERO Clinic, 18 had TEF. Of these, 7 (39%) were female with a mean age of 3.4 years (SD 3), and 44% were Hispanic. Ten TEF patients underwent triple endoscopy and all had at least one abnormal finding. Six were diagnosed with laryngeal cleft (LC); four type I, one type II, and one was unspecified. Other abnormal findings included: bronchomalacia (7), tracheomalacia (8), esophagitis (4), gastritis (2), and duodenitis (1). Additionally, 7 had an abnormal bronchoalveolar lavage (BAL) finding, with 6 culture positive results. Conclusion TEF patients can present with feeding and respiratory difficulties months to years after their surgical repair. The triple endoscopy findings of TEF patients presented in this study illustrate that symptoms may arise from the gastrointestinal or respiratory tract. Our experience with TEF patients at CHLA indicates that a multidisciplinary approach to evaluation and management is necessary to serve the complex needs of this population.

Children's Hospital Los Angeles integrates infant MH care into NICU

In the Early Childhood Mental Health Program at Children's Hospital Los Angeles (CHLA), clinical psychologists Marian Williams, Ph.D.; Patricia Lakatos, Ph.D.; and a team of infant‐family mental health specialists work toward greater mental health awareness in the NICU, Business Wire reported. Infants may not be the first age group that comes to mind in discussions of mental health. Yet, for babies in critical medical condition, Lakatos says an “infant mental health–informed perspective” could reduce stress and improve bonding with parents. This means focusing on not only the physical needs of the child but also the emotional and mental needs, not an easy task for newborn infants who cannot make their voices heard. In an article published in the Journal of Clinical Psychology in Medical Settings, Lakatos, Williams, and co‐authors Tamara Matic, M.D., and Melissa Carson, M.D., advocate for a third component of the NICU family — the relationship between baby and parents. “A lot of mental health work in NICUs currently focus[es] on either the mental health of parents or on the baby's development,” says Williams, who is also the director of the Stein Tikun Olam Infant‐Family Mental Health Initiative at CHLA. “We also want to focus on the relationship between babies and their parents.”

Combination Antibiotics Improves Disease Activity and Alters Microbial Communities in Children With Ulcerative Colitis.

Combinations of antibiotics have shown promise in off-label treatment of Inflammatory Bowel Disease (IBD) flares in adult and pediatric patients1–6. In a small pediatric cohort of moderate-severe medically refractory Ulcerative Colitis (UC), half achieved remission with a regimen of 3–4 antibiotics6. The rationale is to decrease mucosal inflammation by altering intestinal microbiota, however, to date no study has documented these changes. We report our experience with combination oral antibiotics in symptomatic pediatric patients with steroid-dependent or -resistant UC, and demonstrate significant alterations in gut microbiota during and after antibiotic therapy with reductions in inflammatory markers.

Geographic health disparities in the Los Angeles pediatric neck abscess population

ObjectiveTo assess geographical sociodemographic differences in neck abscesses that require surgical drainage in Los Angeles.Study Design: retrospective review. MethodsWe reviewed the medical records of 119 consecutive pediatric patients at Children's Hospital Los Angeles (CHLA) from 2014 to 2017 with a diagnosis of a neck abscess requiring incision and drainage. Sociodemographic information including zip code of residence was extracted and analyzed with Chi-square, Fisher's exact test, and multivariate logistic regression. ResultsThe average age of patients with a neck abscess in this study was 3.4 years old, 53.8% were female, 54.6% were Hispanic, and 82.5% had public health insurance. 79% of patients had an abscess located in the superficial neck, and 10.1% had an abscess located in the retropharyngeal space. There were no significant differences in gender, race, type of health insurance, or income between patients that lived within 10 miles of CHLA versus those that lived farther than 10 miles. On multivariate analysis, zip codes with a high volume of neck abscesses were more likely to be lower income neighborhoods. Gender, race, type of health insurance, and distance from CHLA were not associated with zip codes with a high volume of neck abscesses. ConclusionGeographic areas in the greater Los Angeles community with a high volume of neck abscesses requiring incision and drainage at our institution were associated with lower income neighborhoods. Level of evidenceIV.

Geographic health disparities in the Los Angeles pediatric esophageal foreign body population

ObjectiveTo assess geographical sociodemographic differences in the pediatric esophageal foreign body population of Los Angeles. MethodsWe retrospectively reviewed the medical records of 128 consecutive pediatric patients at Children's Hospital Los Angeles (CHLA) from 2014 to 2017 with a diagnosis of a retained foreign body in the esophagus removed by rigid or flexible esophagoscopy. Sociodemographic information including zip code of residence was extracted and analyzed with Chi-square, Fisher's exact test, and multivariable logistic regression. ResultsThe average age of patients with a retained esophageal foreign body in this study was 2.5 years old, 52.3% were male, 91.4% had no past medical history, 53.1% were Hispanic, 82.0% had public health insurance, and 63.3% were transfers from an outside hospital. The most common foreign body removed was a coin. There were no significant differences in gender, race, type of health insurance, or income between patients that lived within 10 miles of CHLA versus farther than 10 miles. On multivariable analysis, zip codes with a high volume of esophageal foreign bodies were more likely to be lower income neighborhoods. Gender, race, type of health insurance, and distance from CHLA were not risk factors for zip codes with a high volume of esophageal foreign bodies. ConclusionGeographic areas in the greater Los Angeles community with a high volume of retained esophageal foreign bodies requiring endoscopic removal at our institution are associated with lower income neighborhoods. Further studies should be performed to better understand health disparities within the U.S. pediatric esophageal foreign body population.

Factors associated with 30-day all-cause hospital readmission after tracheotomy in pediatric patients

ObjectiveTo determine factors associated with post-tracheotomy hospital readmission within 30 days of discharge. MethodsChildren 18 years and younger who underwent tracheotomy at Children's Hospital Los Angeles (CHLA) between 1/1/2005 and 12/31/2013 with at least 30 days of follow-up at CHLA were identified through ICD-9 procedure codes. Patient characteristics and covariates were obtained by linking manual chart review and administrative data. We used multivariate logistic regression to identify the independent association between risk factors and the primary outcome of 30-day all-cause same-hospital readmission. ResultsOf the 273 patients included, the median age at admission was 6 months [interquartile range (IQR): 1–51 months]. Among this primarily male (60.8%) and Hispanic (66.3%) cohort with a high proportion of discharge on positive pressure ventilation (47.1%), the 30-day readmission rate was 22% (n = 60). Of the readmissions, 92% (n = 55) were unplanned and 64% (n = 35) were associated with acute respiratory illnesses. Multivariate regression analysis demonstrated that, among patients ≤12 months, discharge on positive pressure ventilation [adjusted odds ratio (aOR) = 2.88, 95% confidence interval (CI) = 1.19–6.97] was associated with increased odds of readmission, while gastrostomy tube placement during the tracheotomy hospitalization (aOR = 0.42, 95% CI = 0.19–0.96) and prematurity (aOR = 0.35, 95% CI = 0.15–0.83) were associated with decreased odds of readmission. In patients >1 year of age, increased length of hospitalization (aOR = 1.01 per hospital day, 95% CI = 1–1.02) and presence of comorbid malignancy (aOR = 6.03, 95% CI = 1.25–29.16) were associated with increased odds of readmission. ConclusionsOver one-fifth of children undergoing tracheotomy had an unplanned hospital readmission within 30 days after discharge. Because the majority of readmissions were unplanned and due to acute respiratory illnesses, future research should investigate how discharge procedures and improved care coordination may lower readmission rates in high-risk patients (e.g., patients discharged on positive pressure ventilation).

Creating a Professional Ladder for Interpreters for Improvement of Care

Children's Hospital Los Angeles (CHLA), a metropolitan academic medical center, recognized limitations in how the professional interpreters from the Diversity Services Department were used to support effective patient-provider communication across the organization. Given the importance of mitigating language and communication barriers, CHLA sought to minimize clinical and structural barriers to health care for limited English proficiency populations through a comprehensive restructuring of the Diversity Services Department. This approach entailed a new delivery model for hospital language assistance and cultural consultancy resources. The intervention focused on restructuring the Diversity Services Department, redefining priorities, reallocating resources, and redefining the roles of the language staff positions in the department. The language staff role was redesigned to fit a four-level professional career ladder modeled after the professional career ladders commonly used in hospitals for the RN role and other professional disciplines. The approach involved creating new levels of language specialist, each with progressive requirements for performance, leadership, and accountability for patient care outcomes. Language staff in the inpatient, clinic, and emergency department settings worked alongside nurses, physicians, and other disciplines to care for a specific set of patients. The result of this work was a positive culture change resulting in service efficiencies, care improvements, and improved access to language services. A professional career ladder for language staff contributed to improving the quality and access of language services and advancing the interpreting profession by incorporating care coordination support, vital document translation, and cultural consultancy.

Thermal Pain and Pain Anticipation Induce a Decrease in Microvascular Perfusion in Sickle Cell and Normal Subjects

INTRODUCTION: Sickle cell disease is an inherited blood disorder characterized by vaso-occlusive crises (VOC). HbS in red blood cells (RBC) polymerizes rapidly after it releases oxygen to tissues, causing RBC to become rigid. Anything that decreases flow in the microvasculature increases the chance that this flexible-to-rigid transformation occurs causing the rigid blood cell to lodge in the microvasculature, therefore increasing the chance of vaso-occlusion and the risk of VOC. Although hypoxia and stress are known risk factors for crises, the exact mechanism that initiates VOC events is not well known. We have previously shown that transient hypoxia causes parasympathetic withdrawal and sighs cause vasoconstriction more frequently in SCD subjects than in normal controls. Pain is the hallmark of SCD and is a consequence of VOC but has not been considered as a possible trigger of vasoconstriction that may lead to VOC.OBJECTIVES: To determine if heat induced pain causes decrease in peripheral blood flow (PBF) in SCD.METHODS: 30 SCD and 30 control subjects (healthy and sickle cell traits) were recruited at Children's Hospital Los Angeles (CHLA). Quasi-periodic pulses of pain were induced on the right forearm using TSA-II neuro analyzer heating thermode.We implemented a technique using cross correlation analysis to detect changes in complex microvascular flow signals measured bilaterally on the hands, using laser-Doppler flowmeter (LDF), Peripheral Arterial Tonometer (PAT) and photo-plethysmography (PPG).We also measured the average drop from baseline in the microvascular flow during the heat pain. Data were analyzed using one- and two- sample Student t-test.RESULTS: Data on 53 subjects were analyzed. There was a significant correlation between heat pain pulses and PBF responses, as well as a significant drop in blood flow in all study participants (PPG signal, both p<0.001), indicating that heat pain pulses lead to vasoconstriction.Males had higher correlation (p<0.005) and stronger vasoconstriction (p<0.05) during heat stimuli compared to females. Other Signals (LDF and PAT) had a similar pattern but were less significant.The vasoconstriction response consisted of two components, the first one occurred prior to administration of the painful stimulus indicating that anxiety or anticipation of pain causes significant vasoconstriction. Application of the painful stimulus causes further vasoconstriction.CONCLUSIONS: The findings demonstrate a significant decrease in PBF in both SCD and controls in response to heat pain and possibly to pain anticipation. The decrease in PBF could play a critical role in the genesis of VOC in SCD by markedly prolonging microvascular transit time, increasing the likelihood of red cell entrapment when sickle red cells transform from flexible to rigid. Furthermore, the potent vasoconstriction response to pain in SCD means that pain resulting from VOC could potentially trigger a cascade effect in which vasoconstriction could lead to even more serious VOC. Since regional blood flow is regulated by the autonomic nervous system (ANS), which has been described to be dysfunctional in SCD, our study calls attention to the ANS as a factor in the genesis of crisis in this disorder. [Display omitted] DisclosuresNo relevant conflicts of interest to declare.

The Case for Nursing Leaders on Hospital Boards

At Children's Hospital Los Angeles (CHLA), the participation of our chief nursing officer (CNO) as a voting member on our governing board has been crucial to effective functioning in several areas, particularly those that impact the safety and quality of our patient care services, as well as our entire organization's financial and operational efficiency. As a voting member of our Board of Trustees and 2 standing committees, our CNO has a voice that carries authority and credibility, serving as a conduit between her Trustee colleagues and the nursing troops she leads, who constitute more than half of CHLA employees. Our CNO communicates to the board our nurses' concerns and perspective and in return conveys to nurses the information necessary to implement the board's policies and strategic decisions. As we consider how to ensure CHLA's future as a premier pediatric academic medical center, we understand that the results of the board's work would be impaired if it did not take into account the responsibilities and challenges faced by nurses. We would miss a vital contributor if our CNO was not involved in the hospital's governance at the highest levels.

Thyroglossal duct cyst and sinuses: A 20-year Los Angeles experience and lessons learned

BackgroundFirst described in 1920 and later modified in 1928, the Sistrunk procedure substantially reduced the incidence of recurrence of midline neck cysts compared with a local excision or cystectomy. The purpose of this study was to determine if the rate of recurrence was influenced by performing either a ‘classic’ or a ‘modified’ Sistrunk procedure, if the recurrence rate was influenced by the physician's training, how successful we have been in managing patients with a recurrence? Finally, is outpatient surgery safe for Sistrunk procedures? MethodsWe performed a retrospective review of all patients with a thyroglossal duct remnant (TGDR) who were seen at the Children's Hospital Los Angeles (CHLA) from 1990 to 2010. The following data were collected: patient age, gender, presence or absence of a pre-operative infection, imaging studies, type of procedure performed, the attending surgeon's training background, inpatient or outpatient status, and complications. ResultsA total of 128 patients (61% male, 39% female) met the inclusion criteria. The age ranged from 2 months to 14 years (mean of 5.1 years). A total of 137 procedures were performed; 114 (83.2%) for primary and 23 (16.8%) for secondary disease. Complications included post-operative infection (10.9%), recurrence of disease (6.6%), undesirable scar (5.8%), and fistula (2.9%). Surgeons with fellowship-training in pediatric otolaryngology had a recurrence rate of 4.0% and surgeons with fellowship-training in pediatric surgery or pediatric plastic surgery had a recurrence rate of 30.1%. Twenty patients had a ‘classic’ Sistrunk (14.6%) and 117 (85%) had a ‘modified’ procedure. Patients were admitted after surgery in 78 cases (56.9%) and 59 patients (43.1%) had an outpatient (OPD) procedure. ConclusionsThere is no place for cystectomy in the treatment of TGDR. A ‘modified’ Sistrunk procedure is the procedure of choice in both primary and revision cases. Wide local excision of recurrences is required and a ‘classic’ Sistrunk should be considered. Specific training to gain an intimate knowledge of the anatomy in and around the larynx and experience with multiple cases reduces the incidence of recurrence. Outpatient surgery is safe and effective for selected patients who undergo a Sistrunk procedure.

Effect of residential proximity to major roadways on cystic fibrosis exacerbations

Ambient air pollution has been attributed with an increase in exacerbation frequencies among the cystic fibrosis (CF) population. This study correlates exacerbation frequency with proximity to roadways and two criteria air pollutants. Clinical data was extracted from the Cystic Fibrosis Foundation National Patient Registry and Electronic Medical Records at Children's Hospital Los Angeles (CHLA). Average annual air pollutant levels were obtained from selected US Environmental Protection Agency's monitoring stations. Geographic proximity to monitoring stations and roadways were analyzed using spatial mapping software. A total of 145 patients from the CHLA's CF center were characterized by a dichotomous exacerbation category. No significant association was determined between the frequency of exacerbations and exposure to fine particulate matter and ozone levels. Residential proximity to US-designated highways and freeways also did not achieve significance (p = 0.3777) but was noted to be correlated with major arterial roadways (p = 0.0420). Associations of environmental exposures may have important implications for future predictive models of CF clinical outcomes.

Using a Geographic Information System (GIS) to Assess Pediatric Surge Potential After an Earthquake

Geographic information systems (GIS) and geospatial technology (GT) can help hospitals improve plans for postdisaster surge by assessing numbers of potential patients in a catchment area and providing estimates of special needs populations, such as pediatrics. In this study, census-derived variables are computed for blockgroups within a 3-mile radius from Children's Hospital Los Angeles (CHLA) and from Los Angeles County-University of Southern California (LAC-USC) Medical Center. Landslide and liquefaction zones are overlaid on US Census Bureau blockgroups. Units that intersect with the hazard zones are selected for computation of pediatric surge potential in case of an earthquake. In addition, cartographic visualization and cluster analysis are performed on the entire 3-mile study area to identify hot spots of socially vulnerable populations. The results suggest the need for locally specified vulnerability models for pediatric populations. GIS and GT have untapped potential to contribute local specificity to planning for surge potential after a disaster. Although this case focuses on an earthquake hazard, the methodology is appropriate for an all-hazards approach. With the advent of Google Earth, GIS output can now be easily shared with medical personnel for broader application and improvement in planning.

Association of projected transfusional iron burden with treatment intensity in childhood cancer survivors

Packed red blood cell (PRBC) transfusion is a mainstay in childhood cancer treatment, but has potential for inducing iron overload. The purpose of this study was to determine whether treatment intensity is predictive of projected iron burden resulting from PRBC transfusions among survivors of several forms of childhood cancer. This retrospective cohort study involved patients treated at Children's Hospital Los Angeles (CHLA) between June 1, 2004 and December 31, 2009. Clinical/demographic data were abstracted from medical records. Treatment Intensity Level was determined for each patient using a published scale. Adjusted cumulative PRBC transfusion volume for each patient (ml/kg) was used to compute the adjusted total iron burden (mg/kg) based upon the average hematocrit of the product. Median age of the cohort (n = 214) was 7.9 years (range 0.2-20.2). One hundred and fourteen (53.3%) were male and 129 (60.3%) were Hispanic/Latino. Diagnoses included acute leukemia and six solid tumors, management of which represents a range of cancer treatment intensities. The number of transfusions, transfusion volumes, and projected iron burden were significantly increased and exceeded upper limits of normal among patients with higher treatment intensity. Multivariate analysis found younger age and lower hemoglobin at diagnosis to be associated with greater iron burden after adjusting for treatment intensity. Greater treatment intensity is associated with need for more PRBC transfusions, and thus increased risk of iron overload among childhood cancer survivors. Iron overload may represent another clinically significant late effect following childhood cancer treatment.

Choroid plexus tumors; management, outcome, and association with the Li–Fraumeni syndrome: The Children's Hospital Los Angeles (CHLA) experience, 1991–2010

Choroid plexus tumors (CPT) are rare, and predominate in early childhood. An association with the Li-Fraumeni syndrome (LFS) has been reported, but the biological and clinical implications of this association remain poorly defined. We have investigated the clinical features and overall survival of all CPT patients treated at Children's Hospital Los Angeles (CHLA) over a 20-year period, with particular attention to the association of CPT with LFS. A retrospective evaluation of the course of therapy and clinical outcome was undertaken on the 42 patients diagnosed with and treated for CPT at CHLA from January 1991 to December 2010. Any association with multiple primary tumors and family histories consistent with LFS was investigated in all patients. Six of the 42 patients (16.7%), demonstrated either phenotypic and/or genotypic characteristics consistent with LFS, with either a distinct family history of cancer, a synchronous diagnosis of a different type of cancer, or the subsequent development of metachronous cancers. Of 11 patients with choroid plexus carcinoma tested for TP53 germline mutations, four (36.4%) were positive. A single patient with a choroid plexus papilloma had phenotypic characteristics of LFS but tested negative for TP53. Children with CPC appear to have a high frequency of TP53 germline mutations in association with LFS. This raises the question whether all children with CPC should be tested for TP53 germline mutations in order to institute screening to enhance early detection and treatment of subsequent cancers.