Cerebral X-linked Adrenoleukodystrophy Presenting As Enlarging Cavum Vergae Cyst: A Case Report.

The cavum vergae cyst (CVC) is an uncommon brain malformation. Most patients with CVC are asymptomatic and do not require neurosurgical intervention. Separately, cerebral X-linked adrenoleukodystrophy (X-ALD) is one of the phenotypes of a genetic peroxisomal disorder that is seldom managed by neurosurgeons. We report an unusual case of cerebral X-ALD presenting as an enlarging CVC in a child, and discuss its nuances in corroboration with the literature. A previously well six-year-old male presented with confusion and fever. Urgent neuroimaging demonstrated a large CVC with resultant hydrocephalus. Of note, there were symmetrical areas of signal changes in the periventricular white matter bilaterally involving the corpus callosum, thalami, cerebral peduncles, midbrain, and pons in his MRI. Further investigations performed as part of his medical workup reported high plasma concentrations of very long-chain fatty acids (VLCFA). Put together, a diagnosis of cerebral X-ALD was confirmed. Initially, an external ventricular drain was inserted directly into the CVC under stereotaxy to decompress it. Subsequently, endoscopic fenestration of the CVC was performed as the definitive treatment. He recovered uneventfully from the neurosurgical interventions and proceeded for the treatment of his cerebral X-ALD. To our knowledge, this is the first report of cerebral X-ALD presenting as a CVC in a patient. This case adds to the limited literature for both rare conditions and highlights the importance of a multidisciplinary approach to management.

Point of Care Ultrasound Identification of Multiple Rib Fractures in a Pediatric Patient with Osteogenesis Imperfecta Type 3.

Patients with osteogenesis imperfecta (OI) are at an increased risk of pathological rib fractures even if there is no history of trauma. Early and accurate identification of such fractures are crucial for appropriate management. We present a case of a child with OI type 3 with multiple rib fractures who presented with transient cyanosis and increased work of breathing without a history of significant trauma. The patient's chest radiographs were reported to have a single, new right posterior fourth rib fracture and an old, healing anterior fourth rib fracture. A point-of-care ultrasound performed by the attending pediatric emergency physician revealed additional findings of refracture over the old right anterior fourth rib fracture site and a new left posterior third rib fracture. These findings of multiple and bilateral rib fractures better account for the patient's initial presentation. This case highlights the added advantages of ultrasound over conventional chest radiographs in the evaluation and diagnosis of a tachypnoeic pediatric patient with underlying metabolic bone disease and a complex skeletal structure with multiple pathological rib fractures but no chest tenderness.

Paediatric emergency department attendances during COVID-19 and SARS in Singapore.

INTRODUCTION: We evaluated the impact of public health measures on paediatric emergency department attendances during the COVID-19 and severe acute respiratory syndrome (SARS) outbreaks in Singapore. METHODS: Between 1 January 2020 and 31 July 2020, we retrospectively reviewed paediatric emergency department attendances and admissions in a tertiary paediatric hospital in Singapore before and after a national lockdown to combat the spread of COVID-19 in Singapore. Hospital attendances and admissions were compared with data from a corresponding period in 2019 (1 January 2019 to 31 July 2019), as well as during and after the SARS outbreak (1 January 2003 to 31 December 2004). RESULTS: Compared with a corresponding non-outbreak period, emergency department attendances decreased in line with nationwide public health measures during the COVID-19 and SARS outbreaks (2020 and 2003 respectively), before increasing gradually following lifting of restrictions, albeit not to recorded levels before these outbreaks. During the COVID-19 outbreak, mean daily attendances decreased by 40%, from 458 per day in January-July 2019, to 274 per day in January-July 2020. The absolute number of hospital inpatient admissions decreased by 37% from January-July 2019 (19,629) to January-July 2020 (12,304). The proportion of emergency department attendances requiring admission remained similar: 20% in January-July 2019 and 21% in January-July 2020. CONCLUSION: Nationwide public health measures in Singapore have had an impact on paediatric emergency department attendances and hospital inpatient admissions. Data from this study could inform planning and resource allocation for emergency departments in Singapore and internationally.

Spectrum of neuroimaging findings post-proton beam therapy in a large pediatric cohort.

PURPOSE: Proton beam therapy (PBT) is now well established for the treatment of certain pediatric brain tumors. The intrinsic properties of PBT are known to reduce long-term negative effects of photon radiotherapy (PRT). To better understand the intracranial effects of PBT, we analyzed the longitudinal imaging changes in a cohort of children with brain tumors treated by PBT with clinical and radiotherapy dose correlations. MATERIALS AND METHODS: Retrospective imaging review of 46 patients from our hospital with brain tumors treated by PBT. The imaging findings were correlated with clinical and dose parameters. RESULTS: Imaging changes were assessed by reviewing serial magnetic resonance imaging (MRI) scans following PBT over a follow-up period ranging from 1 month to 7 years. Imaging changes were observed in 23 patients undergoing PBT and categorized as pseudoprogression (10 patients, 43%), white matter changes (6 patients, 23%), parenchymal atrophy (6 patients, 23%), and cerebral large vessel arteriopathy (5 patients, 25%). Three patients had more than one type of imaging change. Clinical symptoms attributable to PBT were observed in 13 (28%) patients. CONCLUSION: In accordance with published literature, we found evidence of varied intracranial imaging changes in pediatric brain tumor patients treated with PBT. There was a higher incidence (10%) of large vessel cerebral arteriopathy in our cohort than previously described in the literature. Twenty-eight percent of patients had clinical sequelae as a result of these changes, particularly in the large vessel arteriopathy subgroup, arguing the need for angiographic and perfusion surveillance to pre-empt any morbidities and offer potential neuro-protection.

Assessment of the Understanding of Concussion and Care Protocols Amongst Student Athletes and Coaches: A Qualitative Study.

Background: Pediatric sports-induced concussions have become a topic of interest and concern in the scientific community. Already, the literature is rich with studies that have identified numerous short-term and long-term consequences of childhood sports-induced concussions. However, there are very few studies that have identified how well the students who participate in concussion-prone sports and their coaches understand these consequences and how they can be avoided. This study aimed to explore student athletes' and their coaches' understanding of the concept of concussion and how it is managed both immediately after the injury occurs and during long-term recovery. Methods: This study utilized a qualitative design. The study was conducted in local and international schools in Singapore. Participants were recruited through purposive sampling. 42 student athletes aged 13-18 who participated in rugby, softball, football, cricket, volleyball, and/or water polo were recruited. Fourteen coaches who coached these same sports were also recruited. Four focus groups and three semi-structured interviews were conducted. Data collected were then analyzed with thematic analysis. Risk factors were assessed through four domains of focus: understanding of what concussion is; attitudes toward concussion; existing protocols for treating concussion; and return-to-school and return-to-play protocols. As this is a qualitative study, outcome measures were not identified. Results: Analysis of the data revealed four themes for each group. For student-athletes these included: limited understanding of concussion; non-reporting of injuries; variable supervision of athletes; and a lack of established return-to-school and return-to-play guidelines. For coaches these included: variable understanding of concussion; insufficient formal training in concussion management; limited medical support in managing injuries; and lack of understanding and adherence to return-to-school and return-to-play protocols. Conclusions: Of the themes identified, the most pressing was a lack of clearly defined return-to-play guidelines. This is an urgent issue that needs to be jointly addressed by healthcare professionals and schools with evidence-based guidelines.

Dynamic adaptation to COVID-19 in a Singapore paediatric emergency department.

Singapore was one of the earliest countries affected by the coronavirus disease 2019 (COVID-19) pandemic, with more laboratory-confirmed COVID-19 cases in early February 2020 than any other country outside China. This short report is a narrative review of our tertiary paediatric emergency department (ED) perspective and experience managing the evolving outbreak situation. Logistic considerations included the segregation of the ED into physically separate high-risk, intermediate-risk and low-risk areas, with risk-adapted use of personal protective equipment (PPE) for healthcare personnel in each ED area. Workflow considerations included the progressive introduction of outpatient COVID-19 testing in the ED for enhanced surveillance; adapting the admissions process particularly for high-risk and intermediate-risk cases; and the management of unwell accompanying adult caregivers. Manpower considerations included the reorganisation of medical manpower into modular teams to mitigate the risk of hospital transmission of COVID-19. Future plans for a tiered isolation facility should include structural modifications for the permanent isolation facility such as anterooms for PPE donning/doffing; replication of key ED functions in the tent facility such as a separate resuscitation room and portable X-ray room; and refresher PPE training. Dynamic reassessment of ED workflow processes, in conjunction with the hospital and national public health response, may help in managing this novel disease entity.

Parental knowledge and beliefs on the use of child car restraints in Singapore: a qualitative study.

INTRODUCTION: Road traffic injuries and fatalities represent a significant public health problem. In Singapore, compliance with appropriate child car restraints (CCRs) is poor. We aimed to understand parental knowledge, beliefs and barriers regarding the use of CCRs. METHODS: In this qualitative study, we conducted five focus group discussions with parents who drive with their children in private cars. Participants were recruited using the KK Women's and Children's Hospital's social media page. Guiding questions were derived by consensus following literature review and adaptation to the Singapore context, exploring parental perceptions of CCR use. Focus group interviews were then transcribed and analysed. RESULTS: 33 participants were recruited, with an age range of 28‒46 (mean age 35.5) years. They had a total of 46 children with ages ranging from 2.5 months to 14 years (mean age 4.2 years). Three key themes were identified: parental knowledge regarding CCRs, barriers to CCR use, and suggestions to increase CCR compliance. Barriers to compliance included lack of knowledge, difficult child behaviour and cultural norms. A multipronged approach was proposed to increase CCR use, including educating the public, reinforcing positive behaviour, legal enforcement as a deterrent to non-compliance, increasing CCR installation services, providing CCRs for taxi users and offering financial incentives. CONCLUSION: Non-compliance to CCR use is multidimensional, including multiple potentially modifiable factors. This study could inform ongoing collaborative injury prevention efforts among healthcare professionals, industry partners and the traffic police, using public education and outreach to reduce the burden of road traffic injuries.

Use of Minimal Residual Disease Assessment to Redefine Induction Failure in Pediatric Acute Lymphoblastic Leukemia.

Purpose Our aim was to determine the role of end-of-induction (EOI) minimal residual disease (MRD) assessment in the identification and stratification of induction failure in patients with pediatric acute lymphoblastic leukemia (ALL) and to identify genetic abnormalities that drive disease in these patients. Patients and Methods Analysis included 3,113 patients who were treated in the Medical Research Council UKALL2003 multicenter randomized trial (NCT00222612) between 2003 and 2011. MRD was measured by using standardized real-time quantitative PCR. Median follow-up was 5 years 9 months. Results Fifty-nine patients (1.9%) had morphologic induction failure with 5-year event-free survival (EFS) of 50.7% (95% CI, 37.4 to 64.0) and 5-year overall survival of 57.7% (95% CI, 44.2 to 71.2). Of these, a small proportion of patients with M2 marrow (6 of 44) and a low EOI MRD level (< 0.01%) had 5-year EFS of 100%. Conversely, among patients with morphologic remission 2.3% (61 of 2,633) had high MRD (≥ 5%) and 5-year EFS of 47.0% (95% CI, 32.9 to 61.1), which was similar to those with morphologic induction failure. Redefining induction failure to include morphologic induction failure and/or MRD ≥ 5% identified 3.9% (120 of 3,133 patients) of the trial cohort with 5-year EFS of 48.0% (95% CI, 39.3 to 58.6). Induction failure (morphologic or MRD ≥ 5%) occurred most frequently in T-ALL (10.1%; 39 of 386 T-ALL cases) and B-other ALL, that is, lacking established chromosomal abnormalities (5.6%; 43 of 772 B-other cases). Genetic testing within the B-other group revealed the presence of PDGFRB gene fusions, particularly EBF1-PDGFRB, in almost one third of B-other ALL cases. Conclusion Integration of EOI MRD level with morphology identifies induction failure more precisely than morphology alone. Prevalence of EBF1-PDGFRB fusions in this group highlights the importance of genetic screening to identify abnormalities that may be targets for novel agents.

Tuberculosis-associated Fibrosing Mediastinitis: Case Report and Literature Review.

Fibrosing mediastinitis is a rare condition defined by the presence of fibrotic mediastinal infiltrates that obliterate normal fat planes. It is a late complication of a previous granulomatous infection, such as histoplasmosis or tuberculosis (TB). Due to its rarity, fibrosing mediastinitis is often under-recognized, and the clinical presentation is variable and dependent on the extent of infiltration or encasement of structures within the mediastinum. We present a case of fibrosing mediastinitis in a man with a prior history of TB, who presented with progressive dyspnea and was found to have chronic mediastinal soft tissue opacities and pulmonary hypertension. His diagnosis was delayed due to the lack of recognition of this clinical/radiographic entity. Fibrosing mediastinitis is a rare entity usually caused by granulomatous disease. Most cases develop as a late complication of histoplasmosis or TB. The presence of calcified mediastinal soft tissue infiltrates on advanced chest imaging can be diagnostic of fibrosing mediastinitis in patients with a prior history of a granulomatous infection once active processes such as malignancy are excluded.

Pulmonary Protothecosis in a Pediatric Liver Transplant Patient.

Immunocompromised patients are susceptible to infections from common and unusual microorganisms. Protothecosis is seldom suspected on clinical grounds, yet it is readily diagnosed once detected in the laboratory. We report the first pediatric liver transplant recipient with pulmonary protothecosis, detected during an episode of Pneumocystis jirovecii pneumonia, and we conducted a review of the available literature.

Hydrolysis of α-chloro-substituted 2- and 4-pyridones: rate enhancement by zwitterionic structure.

The hydrolysis of α-chloro-N-methyl-4-pyridone was found to be more than five times faster than that of α-chloro-N-methyl-2-pyridone. Structural studies of 2- and 4-pyridones have revealed the higher polarity and greater extent of zwitterionic content in 4-pyridone. The results are thus consistent with the hypothesis that polarization and higher zwitterionic content in the heterocyclic structures enhances the rate of hydrolysis in α-substituted pyridone and uracil derivatives.

Improved outcome in childhood acute myeloid leukemia in Singapore with the MRC AML 10 protocol.

BACKGROUND: The introduction of the United Kingdom Medical Research Council's 10th AML trial (MRC AML 10) protocol incorporating high-dose anthracycline therapy has improved outcome of children with acute myeloid leukemia (AML). In this study, we review the results of childhood AML therapy in a Singapore university hospital over the last 17 years emphasizing toxicity and outcome. PROCEDURE: Retrospective analysis revealed 34 children with AML between 1988 and 2003. Prior to September 1996, therapy consisted of: POG-8498 (n = 10), others (n = 9). From September 1996, all but one of 15 children received MRC AML 10 treatment. RESULTS: At the time of analysis, 17 had died from disease, and 17 patients were alive among whom 2 had relapsed. MRC AML 10-treated patients (n = 14) had significantly better 3-year overall, event-free, and disease-free survival (74% vs. 35%, 77% vs. 20%, 83% vs. 31%; P = 0.019, P = 0.002, and P = 0.010, respectively) and were likelier to achieve complete remission (CR) than non-MRC AML 10 patients (P = 0.102). Among patients who achieved CR, MRC AML 10-treated patients were significantly more likely to achieve CR after only one cycle of chemotherapy (P = 0.016). Hematologic toxicity was similar among the different regimens (P = 0.9). CONCLUSIONS: These findings suggest that MRC AML 10 treatment results in significantly superior survival, without excess toxicity. Future studies should attempt to elucidate the relative importance of individual MRC AML 10 components and reduce the high cumulative anthracycline dose without compromising outcome.