Pediatric adrenocortical tumors (ACT) are rare aggressive neoplasms with heterogeneous prognosis. Despite extensive efforts, identifying reliable prognostic factors for pediatric patients with ACT remains a challenge. MicroRNA (miRNA) signatures have been associated with cancer diagnosis, treatment response, and prognosis of several types of cancer. However, the role of miRNAs has been poorly explored in pediatric ACT. In this study, we performed miRNA microarray profiling on a cohort of 37 pediatric ACT and nine non-neoplastic adrenal (NNA) samples and evaluated the prognostic significance of abnormally expressed miRNAs using Kaplan-Meier plots, log-rank test and Cox regression analysis. We identified a total of 98 abnormally expressed miRNAs, which expression profile discriminated ACT from NNAs. Among the 98 deregulated miRNAs, 17 presented significant associations with patients’ survival. In addition, higher expression levels of hsa-miR-630, -139-3p, -125a-3p, -574-5p, -596, -564, -1321, and -423-5p and lower expression levels of hsa-miR-377-3p, -126-3p, -410, -136-3p, -29b-3p, -29a-3p, -337-5p, -143-3p, and 140-5p were significantly associated with poor prognosis, tumor relapse, and/or death. Importantly, the expression profile of these 17 miRNAs stratified patients into two groups of ACTs with different clinical outcomes. Although some individual miRNAs exhibit potential prognostic values in ACTs, only the 17 miRNA-based expression clustering was considered an independent prognostic factor for five-year event-free survival (EFS) compared to other clinicopathological features. In conclusion, our study reports for the first time associations between miRNA profiles and childhood ACT prognosis, providing evidence that miRNAs could be useful biomarkers to discriminate patients with favorable and unfavorable clinical outcomes.

A document by Elizabeth Hawkins. Click on the document to view its contents.

Letter to the editor:–Comment on: Hematopoietic stem cell transplant for erythropoietic porphyrias in pediatric patients–Authors:1. Satesh Kumar, 2.Mahima Khatri–correspondence: Satesh Kumar, 4th year MBBS student, Shaheed Mohtarma Benazir Bhutto Medical College Liyari, KarachiAddress: Parsa citi Block E Floor 5th Flat 501 near police headquarter, Garden east Karachi.Contact: +92-3325252902 Email: [email protected] author: Mahima Khatri, final year MBBS student , Dow university of Health sciencesEmail: [email protected]–Word Count for: 484Disclosure: none to declareConflict of interest: none to declareAcknowledgements: none to declareComment on: Hematopoietic stem cell transplant for erythropoietic porphyrias in pediatric patientsTo the editor:We have read with great sincerity the article ”Hematopoietic stem cell transplant for erythropoietic porphyrias in pediatric patients”, YunZu M. Wang et al.1 It was a pleasure for us to read the concisely written article, and we congratulate the authors for their excellent efforts. The authors have succinctly written numerous scenarios. The final message of the article is that hematopoietic stem cell transplant (HSCT) rectifies the defective heme pathway and should be advised early in patients with severe erythropoietic porphyrias to minimize end-organ damage.Based on varied research2,3 on this lethal disease, we agree that HSCT should be considered early in patients to minimize the damage caused by this condition and enable patients to live a healthy lifestyle. However, we would like to mention a few points that we feel would enhance the quality of this article and add to the existing knowledge of this congenital disease. First, we speculate that the matching of samples would have drawn more meticulous results and increased the validity of the findings. The authors have not highlighted whether different mutations other than UROS exist. For instance, three male patients presented with the X-linked GATA1 gene mutation, an erythroid transcription factor on chromosome Xp11.23.2 Additionally, the study’s retrospective nature has limited reporting regimens accordingly, such as case reports in 2004 elaborated proper doses per body weight and intervals, I.e., Thymoglobulin and Busulphan were given at 5 mg/kg per day and cyclophosphamide at 65mg/kg per day as the conditioning regimen.4 Equivalently, prophylactic measures could have expatiated for the prevention of graft-versus-host disease.4 For illustration, patients were given cyclosporine infusion for 42 days with an initial dose of (3 mg/kg) followed by 6 mg/kg for six months orally to prevent any immunologic reaction to transplant.Secondly, as it is established that the immune system of the pediatric population is not well developed, the authors should have mentioned if any workup for infectious etiologies was sent, such as TORCH (Toxoplasmosis, Syphilis, Rubella, Cytomegalovirus, Herpes simplex virus, and HIV) infections.5 Furthermore, with other factors such as any environmental exposure exaggerating possible porphyria, the authors must have provided data on their environment and surroundings since birth, considering it may also impact. Given the health concerns in the paediatrics population, varying ways could be quoted for differential diagnosis, such as a simple bedside method is wood lamp examination of the diaper or urine if available, for coral-red fluorescence.5 Positivity of tests could raise concerns for further investigation, such as porphyrin levels and genetic testing.In addition to these, the authors could have commented on various other possible ways to avoid exposure to light, such as wearing sun-protective clothing and using window filters in cars and homes.2Yet, that could have also negatively impacted children as sunlight is a natural source of vitamin D. Finally, different approaches should be used to improve investigations and treatments. New treatment concepts should be augmented so that other therapeutic options become employable.

Introduction There is lack of diagnostic and treatment resources with variable access to childhood cancer treatment in low- and middle-income countries (LMIC), which may lead to subsequent poor survival. The primary aim of this study is to determine the prevalence and types of T&CM used in Cameroon. Secondarily, we explored determinants of T&CM use, associated costs, perceived benefits and harm, and disclosure of T&CM use to medical team. Method A prospective, cross-sectional survey amongst parents and carers of children younger than 15 years of age who had a cancer diagnosis and received cancer treatment at three Baptist Mission hospitals between November 2017 and February 2019. Results Eighty participants completed the survey. Median patient age was 8.1 years (IQR4.1 – 11.1). There was significant availability (90%) and use (67.5%) of T&CM, while 24% thought T&CM would be good for cancer treatment. Common T&CM remedies included herbs and other plant remedies or teas taken by mouth, prayer for healing purposes and skin cutting. Living more than 5 hours away from the treatment center (p=0.030), anticipated costs (0.028), and a habit of consulting a traditional healer when sick (p=0.006) were associated with the use of T&CM. T&CM was mostly paid for in cash (36.3%) or provided free of charge (20%). Of importance was the fact that nearly half (44%) did not want to disclose the use of TM to their doctor. Conclusion Pediatric oncology patients used T&CM before and during treatment but would be unlikely to disclose to the child’s health care team.

OBJECTIVE  To determine the overall survival (OS) and prognostic factors influencing outcomes in children and adolescents with malignant extracranial germ cell tumours (MEGCTs) in preparation for the development of a harmonised national treatment protocol.METHODS A retrospective folder review was undertaken at nine South African paediatric oncology units to document patient profiles, tumour and treatment-related data and outcomes for all children with biopsy proven MEGCTs from birth up to and including 16 years of age. RESULTS Between 1 January 2000 and 31 December 2015, 218 patients were diagnosed with MEGCTs. Female sex (HR 0.284 p=0.037) and higher socio-economic status (SES) (HR 0.071; p=0.039) were associated with a significantly lower risk of death. Advanced clinical stage at diagnosis significantly affected 5-year OS: stage I -96%; stage II - 94.3%; stage III -75.5%; (p=0.017) and stage IV (60.1%; p<0.001). There was a significant association between earlier stage at presentation and higher SES (p=0.03). Patients with a serum AFP level of more than 33,000 ng/ml at diagnosis had significantly poorer outcomes (p=0.002). The use of chemotherapy significantly improved survival, irrespective of the regimen used (p<0.001). CONCLUSIONS The cohort demonstrated a 5-year OS of 80.3% with an EFS of 75.3%. Stage, the use of chemotherapy and an elevated serum AFP level of more than 33,000ng/ml were independently predictive of outcome. The relationship between SES and outcome is important as the implementation of the new national protocol hopes to standardise care across the socio-economic divide. 

The grander challenge of pediatric oncology: disparities in access to careJoseph Lubega, M.D., M.S., C.P.E.Baylor College of Medicine6701 Fannin St., Ste. 1510 Houston, TX [email protected]: +1 832 822 4242Fax: +1 832 825 1453Word count: 968Short running title: Disparities in access to pediatric cancer careKeywords: pediatric cancer, disparities, global, minoritiesThe excellent survival of children with cancer in the United States (US) is a grand achievement that has been accomplished mainly through five decades of translating biomedical discoveries to the bedside. However, it obscures the significantly inferior survival of racial-ethnic minorities in the US1, 2, and highlights the unconscionably abysmal survival of children with cancer globally3. Intrinsic differences in epidemiology of prognostically relevant tumor and host biological factors contribute to these survival disparities. However, as demonstrated by the fact that the widest survival disparities occur among children with the most curable cancers and risk-groups2,4, the primary driver of inferior survival among minorities and children globally islack of access to effective pediatric cancer care. Discovery of efficacious therapies was/is the grand challenge to pediatric oncology; ensuring access to effective care for all children in the US and globally is the grander challenge of pediatric oncology.Access to health services is a complex construct that includes5: (1) availability of the services to a specific population, (2) adequate supply of the services to the population, (3) ability to utilize the health services, which includes requisite financial (e.g., medical insurance coverage) and social (e.g., flexibility of work schedule to attend medical appointments) resources, and (4) suitability of the services to the socio-cultural context of all demographic groups in the population. For the majority of the world’s children that develop cancer (~80%) and live in low/middle income countries, infrastructure and expertise for evidence-based pediatric oncology services are simply unavailable or are extremely scanty. On the other hand, racial-ethnic minorities in the US also suffer from lack of access to adequate pediatric oncology care despite the apparent abundance of services – suggesting barriers to utilization and/or suitability of services.In this issue of Pediatric Blood & Cancer , Zheng D.J. et al present an evaluation of access to a psychiatry service that is integrated into a children’s cancer center – the Dana-Farber/Boston Children’s Cancer and Blood Disorders Center (DF/BCH) from 2013 to 2017. The authors examined the relationship between utilization of this psychiatry service and patients’ socio-demographic characteristics. Among a sample of 394 children with cancer that were evaluated, racial/ethnic minorities had 52% lower odds of using the psychiatry service. Household material hardship and household income, two indicators of financial deprivation that may be considered the most obvious determinants of service utilization, did not influence utilization of this psychiatry service. For children who utilized the psychiatry service, 88% were diagnosed with a psychiatric disorder, 76% were given a pharmacological therapy and 62% were given a behavioral intervention for their diagnosis. The high occurrence of a specific diagnosis and therapeutic interventions for the children that used the psychiatry services suggest that this is a highly valuable service for children that are referred.Zheng D.J. et al’s findings demonstrate that availability of services does not equate to access, and that it is often difficult to pin-point the underlying reasons. Although racial-ethnic minorities in the US are associated with financial deprivation, financial indicators did not explain the disparity in utilization of psychiatry services at DF/BCH6. This suggests other utilization or suitability factors were at play. Such factors may include stereotypical beliefs, attitudes, or practices in the interactions between minorities and health providers that negatively influence clinical decision-making and effectiveness7. In this case such stereotypes may influence minority children’s or parents’ rapport with their oncology providers and willingness of parents to report mental or behavior symptoms, and oncologists’ suspicion and threshold to make a psychiatric referral. Other practical social-cultural factors such as language barriers can influence utilization of services even when foreign language translators are used, particularly in the culturally sensitive realm of mental illness and behavioral disorders8.Research to identify and quantify these disparities and their underlying mechanisms is critical to devise effective strategies that will overcome the systemic dynamics that deter minority children from accessing optimal cancer care. In the case of Zheng D.J. et al’s findings, it would be very informative to determine the exact nature of the disparity by evaluating whether, (1) minorities were genuinely less likely to require a psychiatric consultation – a potential difference in disease epidemiology, (2) minorities needed psychiatric services but were not referred – suggesting inferior quality of care, (3) minorities were referred but never followed through on the psychiatric referral – a utilization problem. Mixed methods study designs that complement quantitative data with qualitative insights and involving key players (e.g., providers and minority patients in this case), can unveil critical issues around usability and acceptability that often underly under-utilization of services.Global and US disparities in pediatric cancer care and outcomes epitomize the public health adage that discovery of efficacious biomedical interventions does not automatically translate into improved health services and outcomes for those that need them. Whereas many pediatric oncology researchers are acutely aware of the difficulty to translate research innovations into bedside interventions (aka,“the valley of death”)9, most children/families affected by cancer globally are on the wrong side of a pediatric oncology “death canyon” – a complex milieu of financial, social-cultural, business interests, and health systems barriers that lie between them and the bedside (Figure 1). Enough scientific technologies have made it to the bedside to cure them, but only a few children can make it to the bed.Research that bridges efficacious interventions and their delivery to children with cancer is critically needed. In addition to dedicateddisparities research , hybrid designs that build disparity questions in translational, clinical trials, and epidemiology research are likely to be efficient and even more informative. This requires broadening the scope of research teams and meticulous recruitment of appropriate socio-demographic strata of research participants. For global settings where the landscape of health systems infrastructure and organization and social-cultural norms are very different,implementation research is urgently needed to innovate strategies that will enhance the adoption of pediatric cancer best practices that suit the local context.

Background: Male circumcision is a common procedure, generally performed during the newborn period. Bleeding is an uncommon but feared complication of circumcision. Few reports have evaluated circumcision bleeding rates in patients with bleeding disorders. Objectives: To study circumcision bleeding rates in male subjects who were diagnosed later in life with delta-storage pool deficiency (δ-SPD). Methods: We retrospectively reviewed the medical records of male subjects (≤ 18 years of age) who were circumcised without hemostatic prophylaxis prior to δ-SPD diagnosis from 2000-2020. Bleeding rates and severity were the main outcomes evaluated. We collected demographic data, bleeding scores using a validated assessment tool, laboratory data, and platelet electron microscopy results. A descriptive analysis was performed. Results: Twenty-five male subjects were included. The median bleeding score at presentation was 3.5 (range,2-9). The diagnosis was confirmed using platelet electron microscopy. A value of <2 dense granules/platelet was considered abnormal. Circumcision was performed at a median age of 2 days (range, 1 day-4 months). None of the subjects had intraoperative or postoperative bleeding. With a bleeding rate of zero, we suggest that newborn males with a family history of δ-SPD may be safely circumcised without hemostatic prophylaxis. 

Background: ABVD, the standard-of-care in adult Hodgkin lymphoma (HL), has not been directly compared to ABVE-PC, a pediatric regimen designed to reduce late-effects. We aimed to compare the effectiveness and associated toxicities of these two regimens used in the same institution. 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, secondary malignancy, need for 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=0.01). While not statistically significant, response to therapy, assessed by PET/CT where available, mirrored the need for radiation (rapid response 58.3% vs 90.0%, n=34, p=0.11). There was no difference in event-free survival (p=0.63) or overall survival (p=0.37) with a median follow up length of 3.9 years. Conclusion: ABVD and ABVE-PC achieved similar survival outcomes in our single-institution cohort

Background: While rare in children, chylothorax is a significant cause of respiratory morbidity and can lead to malnutrition and immunodeficiency. Historically, the traditional pharmacological treatment has been octreotide. There are several treatments that have been utilized in the past few years including sirolimus, however data regarding their efficacy and outcomes is limited. Furthermore, sirolimus has proven efficacy in complex vascular malformations, and hence, its utility/efficacy in pediatric chylous effusions warrants further investigation. Methods: In this retrospective study at Texas Children’s Hospital, data were extracted for all patients with chylothorax who were treated with sirolimus between 2009 and 2020. Details regarding underlying diagnosis, co-morbidities and number of days from sirolimus initiation to resolution of effusion were collected. Descriptive statistics were used to analyze the study cohort. Results: Initially a total of twelve infants were identified. Among them, seven patients had complete data and were included in the study. The mean duration of sirolimus treatment needed for chest tube removal was 16 days, with a median of 19 days and range of 7- 22 days. Chest tube output corresponded with sirolimus serum trough levels and trended down prior to chest tube removal. Conclusion: With close monitoring, sirolimus is a safe and effective therapy for pediatric lymphatic effusions even in critically-ill infants. The study also demonstrates shorter duration of chest tube requirement after initiation of sirolimus compared to previous studies. Our conclusion is based on a small case series due to the rare incidence of the condition.

Background: The use of parental donors in pediatric haploidentical hematopoietic cell transplantation is increasing, but research on the psychosocial impact of parental donation is currently limited. We conducted a retrospective, qualitative study to explore parental perceptions of the donation process and the impact of being a donor (or non-donor) on parents’ adjustment and coping with their child’s transplant experience. Methods: Parents/caregivers of children who underwent transplantation with a parental donor or a matched unrelated donor (N = 136) participated in interviews and completed an open-ended questionnaire. Both bereaved parents and parents of survivors were surveyed. Results: Six themes were identified in the data: level of understanding and satisfaction; perception of choice; preparation for donation; perceptions of donation and infusion; benefit-finding; and psychological impact of transplantation. Most parents were satisfied with the information they received and reported a good understanding of transplantation and donation procedures. Parents were divided on perspectives of choice, but their responses reflect that the necessity of saving their child’s life does not allow for choice. They described considerable effort to prepare for transplantation, physically, emotionally, and logistically. Parents acknowledged the psychological impact while identifying positive outcomes that resulted from their child’s transplant journey. Conclusions: Results highlight the unique experiences of parental donors and non-donors from the anticipation phase to the completion of their child’s transplant. Additionally, findings inform supportive care guidance by highlighting the need to assess parental donors’ emotional functioning, provide support post-donation, and conduct bereavement follow-up.

Background Collecting symptom, function and adverse event (AE) data directly from children and adolescents undergoing cancer care is more comprehensive and accurate than relying solely on their caregivers or clinicians for their interpretations. We developed the Pediatric Patient-Reported Outcomes version of the Common Terminology Criteria for Adverse Events (Ped-PRO-CTCAE) measurement system with input from children, parents, and clinicians. Here we report how we determined the recommended Ped-PRO-CTCAE item scoring approach. Methods Scoring approaches compared were 1) at the AE attribute (frequency, severity, interference) using ordinal and dichotomous measures, 2) a weighted composite AE item score by AE attribute (0.5 - frequency; 1.0 - severity; 1.5 - interference), and 3) overall number of AEs endorsed. Associations of each AE attribute, AE item score and overall AE score with the PROMIS® Pediatric measures of anxiety, depressive symptoms, and fatigue were examined. The ability of the overall Ped-Pro-CTCAE AE score to identify patients with PROMIS symptom T-scores worse than reference population scores was assessed. Clinician preference for score information display was elicited through interviews. Results The diverse scoring approaches yielded similar outcomes, including positive correlations of the Ped-PRO-CTCAE attributes, AE item score, and the overall AEs score with the PROMIS Pediatric measures. Clinicians preferred the most granular display of scoring information (actual score reported by the child and corresponding descriptive term). Conclusions Although three scoring approaches yielded similar results, we recommend the AE attribute level of one score per Ped-Pro-CTCAE AE attribute for its simplicity of use in clinical care and research.

Comment on: [Pediatric oncology infrastructure and workforce training needs: A report from the Pediatric Oncology East and Mediterranean (POEM) Group]Julietta Simonyan1, Lusine Hakobyan1,2, Medea Anastasiadi1,2, Lilit Sargsyan1,2, Lala Vagharshakyan1,2, Ruzanna Papyan1,2, Lusine Krmoyan1,2, Mihran Martirosyan1, Samvel Danielyan3, Armen Muradyan1, Gevorg Tamamyan1,21 Yerevan State Medical University, Yerevan, Armenia2 Pediatric Cancer and Blood Disorders Center of Armenia, Hematology Center after Prof. R.H. Yeolyan, Yerevan, Armenia3 Hematology Center after Prof. R.H. Yeolyan, Yerevan, Armenia Corresponding Author: Simonyan Julietta, MD, Yerevan State Medical University, Koryun 2, AM0025, Yerevan, Armenia, Phone: +37499492660, Email: [email protected] Main text word count: 546 References: 1 A short running title: First pediatric hematology-oncology fellowship program in Armenia Keywords: pediatric hematology-oncology, fellowship, Armenia In the recent PBC paper by Khan and colleagues1, the pediatric oncology workforce training needs for the East and Mediterranean region were examined and reported. Armenia, as a part of the Pediatric Oncology East and Mediterranean (POEM) Group, was among the study participants and respondents. At the time of the survey in 2018, Armenia didn’t have a pediatric hematology/oncology training program, which was accordingly reported. In this letter, we describe the recent developments in that regard and the establishment of the first pediatric hematology/oncology fellowship program in our country. On September 4, 2014, the Government of the Republic of Armenia (RA) approved a list of narrow medical specialties of the RA, where one unified specialty - pediatric hematology/oncology was mentioned for the first time. Before that, two separate specializations were existing – pediatric hematology and pediatric oncology, and to obtain those qualifications, it was necessary, after the completion of MD program at the medical university (6 or 7 years), to continue either with an oncology residency program (2 years, which later became 3 years), or hematology program (3 years). Both curricula included pediatric and adult programs, accordingly, the fellows were practicing both pediatric and adult medicine. Before 1998 at the Yerevan State Medical University (YSMU), a faculty of Pediatrics existed with a pediatric-only MD program, however, it was closed in 1998. To become a pediatric hematologist or pediatric oncologist, after the pediatric MD program, graduates were entering into hematology or oncology training, focusing on the pediatric part. Taking into account the successful programs implemented into pediatric hematology/oncology in our country, as well as the dedication and willingness of the local specialists and the need for new specialists, on June 26, 2019, the Board of Trustees of YSMU decided to establish the Department of Pediatric Oncology and Hematology, with a “pediatric hematologist-oncologist” fellowship program and on July 1, 2019, by the decree of the Rector of YSMU, the Department was established. The fellowship program has been adapted based on the educational programs of St. Jude Children’s Research Hospital, Dana-Farber/Boston Children’s Cancer and Blood Disorders Center, and the American Board of Pediatrics programs. In the first year, five clinical fellows entered the program, and two hematology fellows of the 2nd and 3rd year, respectively, transferred to our program. During the second year, three more fellows successfully joined the program, so the number of pediatric hematology – oncology fellows became 10. Besides clinical skills and knowledge, special attention was dedicated to the research component of the program, and a mandatory requirement of conducting research and publication of at least one peer-reviewed article in an international reputable journal was introduced for the completion of the fellowship program. Another mandatory requirement for fellows is the knowledge of at least two foreign languages (mostly English and Russian). These two requirements were introduced for the first time in Armenia. It is worth to mention, that within 2 years since its establishment, pediatric hematology and oncology fellowship program became one of the successful programs at the medical university. Although, at the beginning we were thinking that high requirements might add additional difficulties to attract young physicians to join this emotionally and professionally difficult profession, but it was just the opposite: some of the best graduates with the highest performance chose pediatric hematology-oncology and joined the program․References1. Khan MS, Al-Jadiry MF, Tarek N, et al. Pediatric oncology infrastructure and workforce training needs: A report from the Pediatric Oncology East and Mediterranean (POEM) Group. Pediatr Blood Cancer. 2021;68(9). doi:10.1002/PBC.29190

We compared psychosocial functioning of children with cancer and their caregivers in several phases of the COVID-19 pandemic to before COVID-19. One or more questionnaires on health-related quality of life (HRQoL) or fatigue of children or distress of their caregivers was available from 1644 families. In children with cancer, HRQoL was stable throughout the COVID-19 pandemic. Fatigue was slightly lower and sleep somewhat better during the pandemic than before. Caregiver distress was lower in the first pandemic phase, but increased to pre-COVID-19 levels in later phases, indicating that the length and consequences of the pandemic may be weighing on them.

A document by Yashika Charla. Click on the document to view its contents.

Background: Childhood acute lymphoblastic leukemia (ALL) treatment requires numerous lumbar punctures (LPs) with intrathecal (IT) chemotherapy to prevent and treat central nervous system disease. Historically, LPs in this setting are performed using propofol sedation. At our institution, LPs are often alternatively performed under nitrous oxide (N2O). To date, there have been no large scale assessments comparing these sedation methods for this purpose. Procedures: Retrospective cohort study of patients aged 0-31 years with ALL treated between 1/1/2013-12/31/2018 at the Children’s Minnesota Cancer and Blood Disorders Center, including all therapeutic LPs performed in the clinic setting under either propofol or N2O. Results: Among 215 patients and 2677 therapeutic LPs, 56.6% (n = 1515) occurred under N2O with 43.3% (n = 93) of patients using exclusively N2O with all LPs. The incidence of traumatic LPs (RBC ≥ 10 cells/µL) were similar between both treatments (27.3% vs 30.2). Successful IT chemotherapy delivery (99.7% N2O vs 99.8% propofol) did not differ between sedation types. Experiencing a traumatic LP under N2O was associated with a sedation switch for the subsequent LP (aOR 2.40, p=0.002) while older age (aOR 1.08, p<0.0001) and higher BMI percentile (aOR 1.01, p=0.009) were associated with increased likelihood for undergoing a traumatic LP. Conclusion: N2O is an effective sedation option for therapeutic LPs in children with ALL with noninferiority to propofol in terms of IT chemotherapy administration and traumatic LP incidence. For many patients, N2O can effectively replace propofol during LP procedures, which has important safety and quality-of-life implications.

Comment on: Broaching goals-of-care conversations in advancing pediatric cancerChirag Shah[1], Kayden Chahal[1], Ashni Chani[1], Tejas Kotwal[1][1] Department of Life Sciences and Medicine, King’s College London, England, SE1 9RTWord Count: 464 wordsCorresponding Author: Chirag ShahMobile Number: (+44)07446146162E-mail Address: [email protected] Editor,We read with great interest the article by Kaye et al. that highlights an incredibly important and sensitive area of pediatric care planning1. As final year medical students from the UK who have completed a two-month pediatric placement, we were fortunate to have the opportunity to observe similar discussions and would like to share our own experiences in relation to this insightful article.It is critical to have goals of care conversations with pediatric cancer patients and their families to ensure they receive personalised support. These discussions have been linked with a higher quality of care, a decrease in undesirable aggressive treatment and better bereavement adjustment for caregivers2 3. From our own experiences in sitting in on these conversations, we appreciate the difficulty in navigating through these often highly emotive discussions. It should be noted that there should not be a “one gloves fits all” approach as each conversation must be tailored towards each individual patient. We commend the authors for identifying several strategies to help clinicians broach these conversations.The study cohort demographics shows that 47% of the patients were under the age of 12. During our placement we found it was difficult to engage children of this age for these types of conversations and we often solely relied upon parents’ views. It is essential to ascertain what patients and their families expect from these discussions to prevent missed opportunities from occurring. These can include inadequately responding to concerns over disease progression or addressing concerns by focusing on optimistic talk of future4.The paper highlights that goals of care conversations occur in the setting of advancing pediatric cancer care, however it is unclear when in the course of the illness these discussions start and how frequent they are. It is imperative that these discussions are initiated early, so that clinicians can align the care provided with what is most important for the patient. With the dynamic nature of cancer, it is vital that these conversations occur regularly, to allow the patient and their family to express any concerns when there is a change to their condition. It has been outlined that there are sometimes barriers that are perceived by clinicians that hinder discussions being initiated that need to be addressed. These can include the patients lack of capacity to make decisions, patients and family members’ difficulty accepting a poor prognosis and understanding the complications and limitations of life-sustaining treatment5.Consequently, further research is needed to explore the frequency of these conversations, barriers that prevent conversations being initiated and to determine what patients and their families expect, to prevent missed opportunities from occurring. In summary, it is vital that this area of pediatric cancer care continues to be researched. We hope our comments are useful for any future studies that take place.

Comment on: Secondary impacts of constipation in acute lymphoblastic leukemia in U.S. children’s hospitalsRameez Naqvi1, Saif Abbas Chatoo2, Zayn Ahmad31 UCL Medical School2 Cardiff School of Medicine3 Barts and The London School of Medicine and Dentistry* Correspondence to:Rameez Naqvi, UCL Medical School, 74 Huntley St, London WC1E 6DE, Tel.: 07851081725, Email: [email protected] word count 493;Abstract word count: N/A;Brief running title: Letter to the EditorKey words: Chemotherapy, ALL, Pediatric oncologyTables: 0Figures: 0We read, with great interest, the article by Belsky et al. on the effects of constipation in pediatric oncology patients, particularly looking at children who had undergone induction therapy for Acute Lymphoblastic Leukemia (ALL)1. As medical students who have recently had pediatric and oncology placements, we would like to share our thoughts on what we found to be a fascinating topic.The process of diagnosing and treating a child with cancer is an extremely distressing period for the patient and parent/carer of the patient. The majority of parents of pediatric oncology patients are said to be either mildly or severely distressed2. There is also the challenge that lies with the side effects of chemotherapy along with the struggle in communicating with some young children. Due to side effects, patients can present distressed and require hospital admission, under the guise that it is due to their original condition rather than the treatment. We applaud Belsky et al. for including patients who were readmitted in order to seek psychological support for the side effects of their treatment, as this is a factor often overlooked when looking at readmission data.On our placements, the diagnosis of constipation secondary to chemotherapy was difficult to navigate. We found that the side effects of the medication, such as constipation or fatigue, can cause some patient families to feel an incongruency with their agenda and the healthcare providers, as some find it difficult to perceive that the treatment can also cause the child pain. This can cause strain on an already difficult relationship to manage3. Although it was beyond the stated scope of this study, this would be an interesting secondary impact of chemotherapy side effects that can be explored in the same demographic of patients.As mentioned by Belsky et al., it can be difficult to attribute the constipation solely to the medication being used. There are a variety of confounding factors that can arise during induction therapy that can also cause constipation – dietary changes due to hospital admission, lack of water intake due to fatigue and lack of energy to exercise, to name a few. To further expand the study, looking into these factors and their magnitude of effect would provide a clearer understanding of the secondary effects of constipation.The study defined constipation by the presence of a diagnosis code or a patient who is receiving two constipation medications. The author recognizes that patients can receive these medications prophylactically, so ideally there should be a method of investigating the indication in these patients. It must also be said that diagnosis coding means that there is an element of human error which can cause inaccuracies in the data collected. This can be seen in some international studies4.Future retrospective studies should consider investigating the confounding factors and authenticating diagnoses in order to provide a more robust causality. Research into the true effects of chemotherapy in Pediatrics is crucial and we hope to see more research within this field.References:Belsky, J., Batra, S., Stanek, J. and O’Brien, S., 2021. Secondary impacts of constipation in acute lymphoblastic leukemia in U.S. children’s hospitals. Pediatric Blood & Cancer ,.Boyden, J., Hill, D., Nye, R., Bona, K., Johnston, E., Hinds, P., Friebert, S., Kang, T., Hays, R., Hall, M., Wolfe, J. and Feudtner, C., 2021. Pediatric palliative care parents’ distress, financial difficulty, and child symptoms. Journal of Pain and Symptom Management ,.Zarkowski, P. and Aksu, M., 2021. Legal and Ethical Issues in Treating Adolescent Patients. Dental Clinics of North America , 65(4), pp.815-826.Farhan, J., Al-Jummaa, S., Al-Rajhi, A., Al-Rayes, H. and Al-Nasser, A., 2005. Documentation and coding of medical records in a tertiary care center: a pilot study. Annals of Saudi Medicine , 25(1), pp.46-49.

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