SummaryBackgroundIncomplete surgical resection of medulloblastoma is controversially considered a marker of high-risk disease; driving aggressive surgical resections, “second-look” surgeries, and/or intensified chemoradiotherapy. All prior publications evaluating the clinical importance of extent of resection (EOR) failed to account for molecular subgroup. We analysed the prognostic value of EOR across 787 medulloblastoma samples in a subgroup-specific manner.MethodsWe retrospectively identified patients from Medulloblastoma Advanced Genomics International Consortium (MAGIC) centres with a histological diagnosis of medulloblastoma and complete extent of resection and survival data. Specimens were collected from 35 international institutions. Medulloblastoma subgroup affiliation was determined using nanoString gene expression profiling on frozen or formalin-fixed paraffin-embedded tissues. Extent of resection (EOR) based on post-operative imaging was classified as gross total (GTR), near total (NTR, <1·5cm2), or subtotal (STR, ≥ 1·5cm2). Overall survival (OS) and progression-free survival (PFS) multivariable analyses including subgroup, age, metastatic status, geographical location of therapy (North America/Australia vs world), and adjuvant therapy regimen were performed. The primary endpoint was the impact of surgical EOR by molecular subgroup and other clinical variables on OS and PFS.Findings787 medulloblastoma patients (86 WNT, 242 SHH, 163 Group 3, and 296 Group 4) were included in a multivariable Cox model of PFS and OS. The marked benefit of EOR in the overall cohort was greatly attenuated after including molecular subgroup in the multivariable analysis. There was an observed PFS benefit of GTR over STR (hazard ration [HR] 1·45, 95% CI; 1·07–1·96, p=0·02) but there was no observed PFS or OS benefit of GTR over NTR (HR 1·05, 0·71–1·53, p=0·82 and HR 1·14, 0·75–1·72, p=0.55). There was no statistically significant survival benefit to greater EOR for patients with WNT, SHH, or Group 3 patients (HR 1·03, 0·67–1·58, p=0·9 for STR vs. GTR). There was a PFS benefit for GTR over STR in patients with Group 4 medulloblastoma (HR1·97, 1·22–3·17, p=0·01), particularly those with metastatic disease (HR 2·22, 1–4·93, p=0·05). A nomogram based on this multivariable cox proportional hazards model shows the comparably smaller impact of EOR on relative risk for PFS and OS than subgroup affiliation, metastatic status, radiation dose, and adjuvant chemotherapy.InterpretationThe prognostic benefit of EOR for patients with medulloblastoma is attenuated after accounting for molecular subgroup affiliation. Although maximal safe surgical resection should remain the standard of care, surgical removal of small residual portions of medulloblastoma is not recommended when the likelihood of neurological morbidity is high as there is no definitive benefit to GTR over NTR. Our results suggest a re-evaluation of the long-term implications of intensified craniospinal irradiation (36 Gy) in children with small residual portions of medullobla...
he novel coronavirus was first reported in Wuhan, China, in December 2019. Singapore's first confirmed COVID-19 case was reported on January 23, 2020, and from February 6th through 19th, Singapore had the highest number of cases outside of China. The World Health Organization (WHO) formally declared COVID-19 a pandemic on March 11, 2020.For the past 17 years, Singapore had been preparing for such a pandemic since it experienced the Severe Acute Respiratory Syndrome (SARS) in 2003. Preparations for pandemic outbreaks have been a key part of the Singapore government and its healthcare institutions' business continuity planning and enterprise risk management since then.Singapore is also fortunate in that the National Centre of Infectious Disease (NCID) was officially opened in September 2019. The NCID is a 330-bed, state-of-the-art, purpose-built facility designed to strengthen Singapore's capabilities in infectious disease management and prevention, housing clinical services (intensive care, quarantine and isolation facilitates, and operating rooms), the national infectious diseases laboratory, public health, research, training and education, and community engagement under one overarching structure. It became the operation center for the COVID-19 outbreak, with confirmed and suspected patients with COVID-19 initially admitted there and subsequently to the other public hospitals in Singapore.Following the initial reports of the outbreak in China, precautionary measures were escalated to Disease Outbreak Response Condition (DORSCON) Yellow (DORSCON is a color-coded framework that shows the current disease situation, providing the public with general guidelines on what needs to be done to prevent and reduce the impact of infections: https://www.gov.sg/article/ what-do-the-different-dorscon-levels-mean). A govern-
In this article, we review the literature to find out how the epidemiology of this disease has changed through the years and re-visit the basic pathological process of abscess evolution and highlight the new research in the biochemical pathways that initiate and regulate this process. We also highlight how magnetic resonance imaging and its various modalities have improved diagnostic accuracy. Finally, we discuss the pros and cons of traditional open surgery versus newer minimally invasive methods.
Patient age, first healthcare contact, tumor type, and site were significantly related to diagnostic delay in pediatric solid tumors. Our findings reflect factors related to delay in an urban island-state with minimized confounding by healthcare access and geographic factors.
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