Sick Kids Research Articles

After the Worst Day Ever: What Sick Kids Know About Sustaining Hope in Chronic Illness.

After the Worst Day Ever: What Sick Kids Know About Sustaining Hope in Chronic Illness.

After the Worst Day Ever: What Sick Kids Know about Sustaining Hope in Chronic Illness by Duane R Bidwell

<i>After the Worst Day Ever: What Sick Kids Know about Sustaining Hope in Chronic Illness</i> by Duane R Bidwell

HGG-28. THE IMPACT OF CMMRD IN HIGH-GRADE GLIOMA PATIENTS, A RETROSPECTIVE ANALYSIS OF 7 YEARS IN LMIC; AN IRRDC STUDY

Abstract BACKGROUND Constitutional mismatch repair (MMR) deficiency (CMMRD) is a genetic cancer predisposition syndrome presenting among children and young adults. This study is the first to evaluate CMMRD prevalence among high-grade glioma patients in Pakistan, a country with high consanguinity rates. METHODS We reviewed data of patients younger than 18 diagnosed with pediatric high-grade glioma, anaplastic astrocytoma, and diffuse midline glioma with CMMRD testing between 2016 and 2023. Tumor slides of all included cases were prepared and sent to Sick Kids Toronto to review the MMR protein stains via multi-gene panels. RESULTS Forty-five patients were identified (62.3% females); median age of 11. Headache (88.9%) was the most common symptom, followed by vomiting (60%) and seizures (37.8%); median duration of symptoms was two months. Histopathology revealed 73.3% pediatric high-grade glioma, 22.2% Anaplastic Astrocytoma, and 4.4% Diffuse Midline Glioma. Thirty-six patients (80%) had a cerebral tumor, 13.3%, and 6.7% had a posterior fossa and midline tumor, respectively. CMMRD was positive in 15 of 45 patients (33.3%). Eight patients (53.4%) had CMMRD with loss of PMS 2, two (13.3%) had loss of PMS 2 and MLH 1, two (13.3%) had loss of MSH 2, two (13.3%) had loss of MSH 6, and only one patient had loss of MSH 6 and MSH 2. Consanguinity correlated with CMMRD (P=0.045), but family history of malignancy was not significant (P=0.202). One-year overall survival of all patients, with a median follow-up of 4.8 months, was 44.4 %, whereas 1-year overall survival compared to CMMRD was 33.3%, with a median follow-up of 7.2 months (P=0.616) CONCLUSION We found high prevalence of CMMRD among pediatric high-grade glioma patients and patients with consanguinity. The findings of our study emphasize the importance of genetic testing and counseling. Timely accurate diagnosis is essential as decreased response to conventional treatment regimens may increase disease burden.

When doc becomes doc and mom

As the proportion of women entering the veterinary workforce continues to grow, young veterinarians are demonstrating an increasing need for guidance in navigating pregnancy and motherhood while maintaining their role as a veterinarian. As a relatively new issue for many rural practices, the profession lacks a consistent and distinct precedent for maternity leave and what can be expected during pregnancy. One veterinarian’s experience cannot begin to cover what can be expected for ev­eryone, but can provide tips and insight onto navigating these concerns for other new graduates and practice owners. Follow­ing the obvious challenges of pregnancy and then maternity leave comes the more difficult task of juggling on-call, daycare schedules and sick kids with a busy and unpredictable veteri­nary schedule. Finding a balance is not always easy but can be incredibly rewarding with the right mindset.

Sick kids versus whom? Childhood disability and charitable campaigns on Instagram

Platform media are changing the disability charity landscape. This paper employs a hybrid critical disability studies – platform media studies lens to explore the SickKids VS campaign, aiming to ‘fight’ childhood illness and disability. Employing a social media thematic analysis, we analyzed social media content distributed through the campaign, consisting of images, videos, and captions ( n=620). We found three dominant narratives: heroic sick kids, crumbling infrastructure, and informational content. Each trend, we argue, emerges within a changing platform mediascape, whereby charitable audiences must be cultivated and curated over a long-term process, rather than in a single moment, as in telethon fundraising. We ask how disability is framed in each of those narratives, and how disability studies might respond to these formulations in the political economy of platform media. We end by exploring the strategies disability studies can take to combat the marginalizing effects of such charitable campaigns.

Burden of paediatric hospitalisations to the health care system, child and family: a systematic review of Australian studies (1990–2022)

Paediatric hospitalisations represent a significant cost to the health system and cause significant burden to children and their families. Understanding trends in hospitalisation costs can assist with health planning and support strategies across stakeholders. The objective of this systematic review is to examine the trends in costs and burden of paediatric hospitalisations in Australia to help inform policy and promote the well-being of children and their families. Electronic data sources (Embase, Medline, Web of Science, PSYCH-Info, CINAHL and Scopus) were searched from 1990 until December 2022. Any quantitative or qualitative studies conducted in Australian tertiary hospitals were included in the review. Eligible studies were those that included paediatric (<18 years) hospitalisations and reported on economic and/or non-economic costs for the child, family unit and/or health system. Study quality and risk of bias for each study were assessed with the Joanna Briggs Critical Appraisal Tools. We present a summary of the findings of the hospitalisation burden across major diagnostic admission categories and for the child and family unit. The systematic review was registered with Prospero (ID: CRD42021276202). The review summarises a total of 88 studies published between 1990 and December 2022. Overall, the studies identified that paediatric hospitalisations incur significant financial costs, which have not shown significant reductions over time. In-patient direct hospital costs varied depending on the type of treatment and diagnostic condition. The costs per-case were found to range from just below AUD$2000 to AUD$20,000 or more. The financial burden on the family unit included loss of productivity, transport and travel costs. Some studies reported estimates of these costs upward of AUD$500 per day. Studies evaluating 'hospital in the home' options identified significant benefits in reducing hospitalisations and costs without compromising care. Increasing focus on alternative models of care may help alleviate the significant costs associated with paediatric hospitalisation. This research was supported by Hospitals United for Sick Kids (formerly Curing Homesickness).

Understanding impacts of a ransomware on medical and health facilities by utilizing LockBit as a case study

AbstractAll forms of data are meant to be secured. The emergence of a variety of techniques and tactics utilized by malware authors has made recovery difficult. LockBit ransomware has been in the news and the APT behind deployment of this ransomware virus has compromised several organizations. It is important to understand the behavior of such malware, to identify the anti‐analysis stuff it performs and to block it. The APT involved compromised several health and medical facilities including AIIMS in India and Sick Kids Hospital in Canada. Ransomwares are highly impactful family of malware. Impacts may begin from confidential medical information being harvested over a C2 and can go up to rendering medical equipment useless. This article discusses compromised entities and defending strategies that can be used to block LockBit ransomware using any generic SIEM tool. It also explains the need for tools that can survive ransomware encryption, a restart command‐line and can detect the behavioral patterns of such malware. Several samples were collected from various sources; the identities of compromise were collected from strings and behavior of those samples. Several detection mechanisms including YARA, SNORT, and generic HUNT rules have also been discussed.

Management of Brachial Plexus Birth Injury: The SickKids Experience.

This article describes the approach utilized by the multidisciplinary team at Sick Kids Hospital to evaluate and treat patients with brachial plexus birth injury (BPBI). This approach has been informed by more than 30 years of experience treating over 1,800 patients with BPBI and continues to evolve over time. The objective of this article is to provide readers with a practical overview of the Sick Kids approach to the management of infants with BPBI.

Moms’ mitochondria may refresh cells in sick kids

Technique is designed to treat mitochondrial disease.

A Prolonged Outbreak of Human Adenovirus A31 (HAdV-A31) Infection on a Pediatric Hematopoietic Stem Cell Transplantation Ward with Whole Genome Sequencing Evidence of International Linkages.

A surge in hematopoietic stem cell transplantation (HSCT) human adenovirus A31 (HAdV-A31) infections was initially observed in late 2014/2015 at SickKids (SK) Hospital, Toronto, Canada. In response, enhanced laboratory monitoring for all adenovirus infections was conducted. Positive samples underwent genotyping, viral culture, and, in selected cases, whole-genome sequencing (WGS). HAdV-A31 specimens/DNA obtained from four international pediatric HSCT centers also underwent WGS. During the SK outbreak period (27 October 2014 to 31 October 2018), 17/20 HAdV-A31 isolates formed a distinct clade with 0 to 8 mutations between the closest neighbors. Surveillance before and after the outbreak detected six additional HAdV-A31 HSCT cases; three of the four sequenced cases clustered within the outbreak clade. Two SK outbreak isolates were identical to sequences from two patients in an outbreak in England. Three SK non-outbreak sequences also had high sequence similarity to strains from three international centers. Environmental PCR testing of the HSCT ward showed significant adenovirus contamination. Despite intense infection control efforts, we observed re-occurrence of infection with the outbreak strain. Severe but nonfatal infection was observed more commonly with HAdV-A31 compared to other genotypes, except HAdV-C1. Our findings strongly implicate nosocomial spread of HAdV-A31 over 10 years on a HSCT unit and demonstrate the value of WGS in defining and mapping the outbreak. Close linkages among strains in different countries suggest international dissemination, though the mechanism is undetermined. This large, extended outbreak emphasizes the pre-eminent role of HAdV-A31 in causing intractable pediatric HSCT outbreaks of severe illness worldwide.

Early Findings on the Use of Motion Capture during Simulated Sports Activities to Better Understand Hemophilic Arthropathy

Many persons with hemophilia (PwH) have joint bleeding despite prophylaxis. We hypothesize that movement biomechanics play a significant and largely unexplored role in joint bleeding, which could be exploited to develop personalized rehabilitation programs. We have designed a clinical study to test this hypothesis. Here we show data from the first 3 enrollees as case studies of what could potentially be learned.Data were collected from 3 participants with hemophilia A, ages 10-30 years, on prophylaxis with emicizumab, with at least 1 joint bleed in the lower extremity in the past year, using motion capture techniques with force plates and reflective markers collected through a Vicon system. Motion lab activities were designed to simulate sports activities and included walking (barefoot and shod), squatting (double and single leg), hopping on one foot, and jumping from a 30-cm box. Two patients (B and C) routinely take additional factor VIII prophylaxis prior to physical activity and did so before coming to the motion lab. Hemophilia Joint Health Score (HJHS) was obtained by an experienced physical therapist prior to motion lab collection to gauge degree of hemophilic arthropathy by physical exam. A subset of participants and activities are shown graphically.Participant A (not shown) had a higher HJHS in the right knee than left (3 vs 0) and had HJHS of 4 in bilateral ankles, with most recent bleed in the right ankle 8 months prior; primary physical activity was walking. This participant showed subtle differences between the right and left in all activities, including less weight on the right leg during double leg squat, and right single leg hop lower than the left.Participant B had a higher HJHS in the right knee than the left (3 vs 0) and in the right ankle than the left (7 vs 6), and he had had multiple episodes of knee pain but no change in HJHS since 2 years prior. Knee MRIs performed outside of the study were consistent with tendinosis of bilateral quadriceps rather than bleeding. Primary sports were basketball, hiking, biking, and skiing. Participant B had subtle differences between the right and left side that seemed to protect the right, including mildly decreased right knee flexion with weight acceptance during walking (more pronounced when wearing shoes), lower power generation by the right ankle than the left in walking, and lower peak ground reaction force (GRF) on the right than left in forward hopping. Some motions seemed to protect the left side more, with less power generation and absorption by the ankle (double and single leg squats) and hip (single leg squat only), right single leg squat somewhat deeper than the left, and slower time to step onto the left foot than the right.Participant C had a higher HJHS in the right knee than left (2 vs 1) and in the right ankle than left (5 vs 3) but had had worsening HJHS in bilateral ankles compared to his previous scores, with bleeds in both knees in the past year. Primary physical activities were baseball (pitching), basketball, biking, skiing, and golf. He had recently been diagnosed with Osgood Schlatter (patellar tendon/tibial tuberosity inflammation) of the left knee, which had been causing pain for several months, but no bleeding in that knee. Movement analysis reflected left knee pain, including very little flexion with weight acceptance when walking; very little power absorption or generation from the knee in walking, hopping, and squatting; shallower squats and lower hops on the left; and lower ground reaction force on the left than the right with walking. Perhaps related to the left knee protection, both ankles were consistently more plantarflexed in walking, and there was increased power generation in the right ankle compared to the left.These findings suggest the presence of subtle asymmetry related to hemophilic arthropathy and previous bleeding, which were more pronounced in more strenuous activities than with walking. The results of participant C could suggest that pain, even if unrelated to hemophilia, could cause compensatory movement mechanisms that could lead to increased bleeding risk in other lower extremity joints.Ongoing analysis will include tracking of bleeding over 1 year following motion analysis, enrollment of additional participants, comparison with controls, and performing detailed statistical analysis to determine which movement parameters correlate best with HJHS and lower extremity bleeding risk. [Display omitted] DisclosuresWarren: Novo Nordisk: Consultancy; Hema Biologics: Consultancy; Bayer: Research Funding; CSL Behring: Research Funding; Genentech: Research Funding. Funk: Biomarin: Consultancy; Sanofi Genzyme: Speakers Bureau; Toronto Sick Kids Hospital: Patents & Royalties: Hemophilia Joint Health Score Royalties; Partners: Honoraria.

LGG-34. CLINICAL AND MOLECULAR CHARACTERIZATION OF A MULTI-INSTITUTIONAL COHORT OF PEDIATRIC SPINAL CORD LOW-GRADE GLIOMAS

BACKGROUNDThe MAPK/ERK pathway is involved in cell growth and proliferation, and mutations in the BRAF paralog of this pathway have made it an oncogene of interest in pediatric cancer. Previous studies have identified that BRAF mutations as well as BRAF-KIAA1549 fusions are common in intracranial low-grade gliomas (LGGs). Fewer studies have tested for the presence of these genetic aberrations in spinal LGGs. The aim of this study was to better understand the prevalence of BRAF and other genetic aberrations in spinal LGG.METHODSWe analyzed 46 spinal LGGs from children age 1–25 years from two institutions, Children’s Hospital Colorado (CHCO) and The Hospital for Sick Children (Sick Kids) for the presence of BRAF fusions or mutations. Data was correlated with clinical information. A 67 gene panel additionally screened for other possible genetic abnormalities of interest in the patient cohort from CHCO. In the Sick Kids cohort, BRAFV600E was tested for by ddPCR and IHC while BRAF fusions where detected by FISH, RT-PCR or Nanostring platform.RESULTSOf the 31 patient samples who underwent fusion analysis, 13 (42%) harbored the BRAF-KIAA1549 fusion. Overall survival (OS) for patients confirmed positive for BRAF-KIAA1549 was 100% compared to 76% for fusion negative patients. Other mutations of interest were also identified in this patient cohort including BRAFV600E, STK11, PTPN11, H3F3A, APC, TP53, PIK3CA (polymorphism), FGFR1, and CDKN2A deletion.CONCLUSION BRAF-KIAA1549 was seen in higher frequency than BRAFV600E or other genetic aberrations in pediatric spinal LGGs and trends towards longer OS although not statistically significant.

Serum Cortisol and Urinary Vanillyl Mandelic Acid Levels in Critically Ill Children

The term fundamentally sick youngster doesn't allude to a specific illness yet it alludes to any kid who is in a clinical state which may bring about respiratory or heart failure or cut off neurologic complexities if not perceived and treated expeditiously. The point of this postulation wass to decide the scope of serum cortisol and urinary Vanillyl Mandelic Acid (VMA) levels in a gathering of basically sick kids and correspond them to seriousness and result. This cross sectional examination included 40 pediatric patients going from 1month to 18years Acute Physiology and Chronic Health Evaluation II(APACHE II) scoring framework which depends on deviations from typical of 11acute physiologic variablesAll patients had been researched for Assessment of cortisol level (ELISA) and VMA leve. Mean APACHE II score was essentially higher in non-survivors (20) contrasted with 12 in non-survivors. Middle Cortisol level was essentially higher in non-survivors (50) contrasted with survivors (20). Middle VMA was altogether higher in non-survivors (41) contrasted with survivors (10). Cortisol and VMA levels are raised in non-survivors contrasted with survivors. We recommend that the accompanying admonitions be borne as a main priority when diagnosing adrenal inadequacy in the basically sick patient.

The influence of selenium deficiency on chosen biochemical parameters and histopathological changes in muscles of goat kids.

The research was conducted on 40 young alpine goats (kids) divided into two groups. First group consisted of 20 kids demonstrating clinical signs of muscular dystrophy. Second group was a control and consisted of 20 animals that received intramuscular injection (2ml per animal) of vitamin E and selenium preparation containing in 1ml 50 mg of tocopherol acetate, 0.5mg of sodium selenite and solvent on 2nd day of life. The kids were clinically examined and blood for laboratory analyses was sampled three times from day 5 of their life in 10 day intervals. In addition, six 24 days old kids demonstrating clinical signs of muscular dystrophy and six control kids were subjected to biceps femoris biopsy. Serum total protein, glucose, triglycerides, cholesterol as well as AST, CK and LDH were determined in all the animals. In addition, the activity of glutathione peroxidase (GSH-Px) was determined in whole blood and serum concentrations of selenium and vitamin E were deter-mined in 6 kids from each group. Total lactate dehydrogenase activity and its separation into isoenzymatic fractions were determined in the collected biopsy material. The muscle samples collected were additionally subjected to histopathological examination consisting of HE staining and HBFP staining to detect necrotic muscle fibers. Symptoms of muscular dystrophy began to appear in the first group between 17 and 23 days of age and included tremors of the limbs, poor posture, stilt gait and increased time of laying. The control animals did not show any symptoms of the disease during the experiment. Hypo-proteinemia, hypoglycemia, cholesterol reduction and elevated triglycerides level associated with lipolysis of adipose tissue have been found in the sick kids. A significant decrease in selenium, vitamin E and activity of glutathione peroxidase levels was observed in the kids with symptoms of muscular dystrophy. The activity of AST, CK and LDH was significantly higher in the animals with symptoms of the disease as well. Five isoenzymes were obtained in the electrophoretic separation of lactate dehydrogenase into isoenzymatic fractions in the muscle tissue. LDH4and LDH5 isoenzymes were dominating, and a significant increase in LDH5 fraction of the sick animals was also observed. Histopathological examination of muscle samples from sick animals revealed changes characteristic for the presence of Zenker necrosis.

179-LB: Characteristics of Children with Medication-Induced Diabetes (MID): A Canadian Pediatric Surveillance Program (CPSP) Study

Objectives: There is limited data on MID in children. This study aimed to compare the demographic and clinical characteristics of 1) a historical MID cohort to a new cohort and 2) children with MID based on overweight/obese BMI (O-BMI) and normal weight BMI (N-BMI). Methods: National surveillance was conducted via the CPSP. Pediatric clinicians reported new cases (children &amp;lt;18 years old) of non-type 1 diabetes for 24-months (cohort 1: 2006-08, cohort 2: 2017-19). MID cases were classified by the presence of diabetes as defined by Diabetes Canada and exposure to a diabetogenic medication. Comparisons were made between the two cohorts and between MID patients with O-BMI (BMI ≥85th percentile for age and sex) and N-BMI (BMI &amp;lt;85th percentile for age and sex). Descriptive statistics and Fisher exact, chi-squared and t-tests were used where applicable. Results: There were 55 cases of MID in cohort 1 and 51 cases in cohort 2, with no significant differences between cohorts. Mean age (+/- SD) at presentation was 13.1 +/- 3.6 years and 13.3 +/- 3.5 years in cohort 1 and 2, respectively. Glucocorticoid therapy was documented in &amp;gt;95% of cases in both cohorts. In the combined cohorts there were 50 cases with N-BMI and 43 cases with O-BMI. There were no statistically significant differences in age, sex or ethnicity across BMI groups. Mean hemoglobin A1c (+/- SD) (n = 40) was 6.45% +/- 1.11% in the N-BMI group and 7.26% +/- 2.51% in the O-BMI group (p = 0.184). The O-BMI group were more likely to have a parent with type 2 diabetes (T2D) (p = 0.042) and acanthosis nigricans (p = 0.007) compared to the N-BMI group. Conclusions: The demographic and clinical features of children with MID have not changed over a 10-year period. The presence of acanthosis nigricans and/or a parent with T2D may be used to identify children who require more intensive glycemic monitoring when on a diabetogenic medication. Further studies are needed to better understand the evolution of MID and the risk it confers to developing T2D. Disclosure T.J. Patel: None. A. Ayub: None. M.A. Irvine: None. S. Hadjiyannakis: None. M. Henderson: None. M.A. Nour: None. T. Pinto: None. B. Wicklow: None. J. Hamilton: None. E. Sellers: None. S. Amed: None. Funding Diabetes Canada; Manitoba Institute for Child Health and Sick Kids Hospital; Public Health Agency of Canada (F18-02353)

Public Perception of a Normal Head Shape in Children With Sagittal Craniosynostosis

Twenty-two unique images were presented via an online crowdsourcing survey of a severe case of non-syndromic sagittal craniosynosis gradually corrected to an age and gender matched normalized head shape. Participants were recruited via the Sick Kids Twitter account. Participants were invited to rate the head shapes as "normal" or "abnormal." The 538 participants completed the online survey. Participants were able to reliably and consistently identify normal and abnormal head shapes with a Kappa Score >0.775. Furthermore, participants indicated that a correction of 70% is required in order for the cranial deformity to be regarded as "normal." This threshold closely reflects a normal Cranial Index, which is a widely used morphometric outcome in craniosynostosis. Crowdsourcing provides an ideal method for capturing the general population's perspective on what constitutes a normal and acceptable head shape in children with sagittal craniosynostosis. Laypersons are able to reliably and consistently distinguish cranial deformities from a "normal" head shape. The public indicates a threshold correction of 70% in sagittal craniosynosis to regard it as a "normal" head shape.

The Age of Hubris.

Apps don’t help parents of sick kids.1 A recent systematic review of research relating to apps and their use in helping parents of ill children found an absence of evidence of benefit but evidence of user dissatisfaction. We are in the midst of the Information Age, but I suspect that a combination of outcomes is something we are all familiar with, whether users of such apps or not. Wikipedia identifies the development of the transistor as the fundamental facilitator to the ending of the earlier Industrial Age,2 shifting us to an economy primarily based on information technology; that economy includes plenty of failed promises still. I contend that this is in fact the Age of Hubris. It is salutary to think how little we still …

A110 DGAT1 MUTATION OF LIPID TRAFFICKING ASSOCIATED WITH A RARE CASE OF CONGENITAL DIARRHEA

Abstract Background Congenital diarrheas and enteropathies (CODEs) are rare and cause severe chronic diarrhea in children under 2 years of age.1 Current genomic research has identified several monogenic defects resulting in epithelial disorders of nutrient and electrolyte transport, enzymes function, metabolism and trafficking. Aims To discuss a rare case of congential diarrhea. Methods Case Report. Results A 10-month-old Ashkenazi Jewish boy was referred to Pediatric Gastroenterology for loose stools and failure to thrive. Born at 27 weeks, he was a NICU inpatient for his first 3 months of life. Explosive loose stools were first noticed after discharge and treated as cow’s milk protein allergy. At aged 10 months he was admitted to his local hospital with irritability, abdominal distension, foul smelling loose stools and developmental delay. Despite an intake of 130kcal/kg/day he failed to gain weight (weight and length &amp;lt; 3rd centile). His abdomen was distended but there was no organomegaly on examination. On transfer to Sick Kids he underwent extensive work up with low albumin 24 g/L but normal CBC, amylase, lipase and IgA and anti-TTG negative. The lipid profile showed hypertriglyceridemia 2.98 mmol/L (normal &amp;lt;0.85), low HDL 0.81 mmol/L but normal total cholesterol. Low apoliprotein A1 0.79 g/L (0.92 - 1.96), low apoliprotein B 0.54 g (0.59 - 1.46) and vitamin E deficiency 9.6 umol/L (14.5 - 33.0). Normal fecal elastase (&amp;gt; 500 ug/g stool). Upper GI endoscopy showed duodenal villi blunting with non-specific chronic inactive duodenitis on histopathology. Due to ongoing poor weight gain he commenced TPN. A repeat endoscopy four weeks after admission revealed patchy villous blunting, crypt hyperplasia and enterocyte vacuolization. However, ultrastructural electron microscopy examination showed normal enterocyte brush border with well-formed microvilli with no inclusions or vesicular bodies. With a differential diagnosis of chylomicron retention disorder, abetalipoproteinemia or hypolipoproteinemia he was commenced on a low-fat diet with MCT feeds. A 72-hour fecal fat collection on this diet was within normal range 5.4 mmol/day (2–7). One year later his weight is now on 3rd centile and his albumin levels have normalized. However, triglycerides remain elevated. Whole exome sequencing identified two pathogenic variants in the DGAT1 gene; c.629_631delCCT, pSer210del and c751 + 2T&amp;gt;C, IVSB+2T&amp;gt;C. Conclusions Diacylglycerol acyltransferase (DGAT)1 catalyzes triglyceride biosynthesis.2 Loss of function DGAT1 gene mutations are described in several cases studies3,4 characterized by electrolyte transport–related diarrhea, protein-losing enteropathy and growth failure. Our cases adds to the understanding of the phenotypic and histological spectrum of DGAT1 mutations. Management strategies currently focus on growth with dietary lipid restriction, while substituting fat-soluble vitamins and essential fatty acids. Funding Agencies CAG

Robin Paul Humphreys 1937-2020+

Robin Paul Humphreys was born on 16 October 1937 in Edmonton, Alberta, Canada. He was admitted to the University of Toronto, Faculty of Medicine, in 1956, became the Class President for the academic year 1957-58, and was awarded the Webster Scholarship in the year of his graduation (1962). His internship was of the rotatory variety, served at St. Michael's Hospital in Toronto, and then in 1963 he embarked upon his postgraduate studies in orthopedic surgery at the University of Toronto, where he worked on the clinical staff for 2 years before going into the laboratory to do investigative work under the direction of Robert Salter. It was during this period of experimental work that reflection and introspection brought him to the decision to leave orthopedic surgery, enter neurological surgery, and to work under the tutelage of Thomas R Morley at the Toronto General Hospital, where he remained until 1970, at which time he completed his postgraduate studies. That same year he was accepted as a Fellow of the Royal College of Physicians and Surgeons (FRCS, Canada), and was appointed an Associate in the Department of Surgery of the University of Toronto. Dr. Robin P. Humphreys joined the neurosurgical staff at the Hospital for Sick Children (Sick Kids) in 1970. He initiated the Craniofacial Program at Sick Kids with Dr. Ian Munro, and over the years became a world authority on the management of children with spina bifida and vascular malformations. He also to structure the postgraduate educational program for the neurosurgical residents and fellows. Many Brazilian neurosurgeons spent some time as fellow or visiting the Sick Kids and had the privilege and pleasure of meeting with him. He was President of the American Society of Pediatric Neurosurgeons (ASPN) from 1992 to 1993, and of the the International Society for Pediatric Neurosurgery (ISPN) from 1993 to 1994. Dr. Humphreys was Neurosurgeon-in-Chief at Sick Kids from 1996 to 2003. All of us in pediatric neurosurgery know that during that period at the Hospital for Sick Children (Sick Kids) there were a remarkable team that was known as three H's – Bruce Hendrick, Harold Hoffman, Robin Humphreys - who were dubbed He, Ho, and Hum, each taking on special activities. Dr. Humphreys published over 200 papers during his career. May Dr. Humphreys rest in peace!

Predictors of Posterior Fossa Syndrome: Results From an International Multicenter Cohort Study of Molecularly Characterized Medulloblastoma Patients

Abstract INTRODUCTION Posterior Fossa Syndrome (PFS) is a common complication following surgical resection of pediatric posterior fossa tumors. PFS is characterized by a combination of mutism, ataxia, and other behavioral symptoms that typically improves within weeks to months. Medulloblastoma histology, midline location, and brainstem invasion increase risk for PFS. Medulloblastoma subgroups have historically been treated as a single entity when assessing PFS risk, however, recent studies highlighting their clinical heterogeneity suggest the need for a subgroup-specific analysis of PFS risk. Here, we examine a large international multicenter cohort of molecularly characterized medulloblastoma patients to assess predictors of PFS. METHODS We assembled a cohort of 270 medulloblastoma patients from 4 sites including Christian Medical College and Hospital (n = 87), Great Ormond Street Hospital (n = 25), Hospital for Sick Kids (n = 111), and Stanford University Medical Center (n = 47), who underwent surgical treatment of medulloblastoma and had molecular subgrouping of their tumors. Patient age at diagnosis, gender, tumor volume, and PFS status were assessed in addition to molecular subgroup. RESULTS Overall, 25.9% of our cohort developed PFS. PFS patients were younger (mean difference −2.73 yr ± 0.8, P = .0009) and had larger tumors (mean difference 16.99 cm3 ± 5.287, P = .0015) that were more midline (OR = 20.03, P &lt; .0001). On multivariate analysis adjusting for age, sex, midline location, and tumor volume, WNT (adjusted OR = 5.19, P = .022) and Group 4 (adjusted OR = 7.15, P = .004) tumors were found to be independently associated with higher risk of PFS as compared to SHH tumors. CONCLUSION Here, we present the largest molecularly characterized cohort of medulloblastoma patients in the context of PFS development. In combination with recent data showing that WNT and Group 4 tumors have a longer pre-diagnostic interval our results support the hypothesis that large midline tumors that grow slowly have a higher risk of PFS.