Diagnosis Of Pediatric Patients Research Articles

P464: COMPARED TO CLASSICAL CYTOGENETICS OPTICAL GENOME MAPPING (OGM) DETECTS MULTIPLE ADDITIONAL STRUCTURAL CHROMOSOMAL ABERRATIONS IN PEDIATRIC ACUTE MYELOID LEUKEMIA (AML)

Background: AML is the 2nd most frequently diagnosed blood cancer in children affecting approximately 130 patients annually in Germany. Pediatric AML is a heterogeneous malignancy that has multiple genetic aberrations. This is relevant for classification, prognosis and selection of optimal therapy. To detect these alterations established procedures (karyotyping, FISH, RNA-based techniques) are used with well-known limitations (resolution of karyotyping and FISH, respectively; cell cultivation is necessary to generate metaphases; cost-intensiveness; necessity of experienced and intensively trained staff). OGM is an emerging technique addressing these limitations. Based on extraction of ultra-high weight DNA followed by fluorescent labelling at the sequence CTTAAG a barcode-like pattern of the genomic DNA is created. The DNA strands labelled in this way are stretched and drawn as single ultra-long fragments through nanochannels. The results are translated into molecule maps which are compared to the reference genome (resolution down to 500 bp) allowing the identification of genetic alterations. This method combines high resolution with picturing almost whole chromosomes without cell cultivation. Aims: The aim of this study was to test to what extend OGM might supplement classical cytogenetics (CCG) to detect risk defining genetic aberrations at initial diagnosis in pediatric patients with AML. Methods: We analyzed 24 specimen of pediatric AML, MPAL and bilineage leukemia patients by OGM starting from stored frozen material (bone marrow, peripheral blood) obtained at initial diagnosis. Results of OGM were compared with karyotyping and FISH. Primer walking and breakpoint spanning PCR were used to validate newly detected aberrations by OGM in selected cases. Applying breakpoint-spanning PCR, validated aberrations were used as markers for assessment of minimal residual disease (MRD) in selected cases during AML treatment. Results: Overall, we detected discrepant results between CCG and OGM in 17/24 (70%) cases including 9 cases in which karyotyping detected aberrations which were not found by OGM. However, these aberrations were not relevant for risk stratification. In general, focusing on genetic aberrations important for risk stratification the results between CCG and OGM were concordant in 23/24 (96%) cases. In a single case OGM was able to detect a high-risk aberration which was missed by CCG. In total, 33 previously unknown genetic alterations were identified by OGM. Out of these four newly detected variants (2 deletions, 2 translocations) were validated by PCR. The translocations t(2;12) and t(8,12) both affected gene ETV6 on chr. 12 with different fusion partners (chr. 2: AC064875.1; chr. 8: NSMCE2). In both translocations sequences at the breakpoints were determined. Two deletions affecting genes RNF157 on chr. 17 and MEF2B on chr. 19 were validated. These aberrations had not been described before in pediatric AML. In 2 cases - both without a previously identified MRD marker – the newly detected translocations by OGM were used for MRD monitoring. Summary/Conclusion: OGM considerably expands the range of techniques to optimize the diagnosis of pediatric AML and has much potential to omit limitations of classical cytogenetics. Furthermore, the results will contribute to a better understanding of the leukemogenesis of pediatric AML. In addition, OGM offers the possibility to identify new aberrations which can serve as patient specific MRD markers especially in cases without a previously known MRD marker.

An examination of effects of intimate partner violence on children: A cross-sectional study conducted in a paediatric emergency unit in Turkey.

Intimate partner violence (IPV) against women causes inadequate and unbalanced nutrition in children aged 0-5years and adversely affects their growth. To examine the impact of intimate partner violence on a child's growth regarding the medical diagnosis in paediatric patients under 5years of age, growth of the child, and the mother's exposure to intimate partner violence. This descriptive cross-sectional study included 166 children admitted to a paediatric emergency department, and their mothers. Women exposed to emotional violence and controlling behaviour during pregnancy had children prone to being overweight and obese. A mothers lifetime exposure to physical violence had an adverse effect on their children's wasting and moderate wasting. In contrast, mothers' exposure to emotional violence had a direct impact on a child's wasting and moderate wasting. The lifetime effect of domestic violence may begin at birth. This vulnerability leads to negative outcomes in both children and women regarding biopsychosocial development. Nurses and midwives in primary health care services and one-on-one care should be trained to evaluate prospective mothers and children aged 0-5 regarding violence and its effects on the child's growth.

Prevalence of food allergy diagnosis in pediatric patients with atopic dermatitis referred to allergy and/or dermatology subspecialty clinics

Atopic dermatitis (AD) is a common chronic inflammatory pediatric skin disorder, affecting up to 25% of children.1 Children with AD are at higher risk for food allergy (FA); approximately 30% to 50% of children with AD have a history of FA.2-5 Further, the prevalence of AD and FA has increased over time.6 Prior studies examining FA prevalence in children with AD often conflated multiple types of FA, including immediate immunoglobulin E (IgE)–mediated symptoms and food-triggered atopic dermatitis (FTAD), and did not clearly distinguish the two entities.

OTHR-11. The effects of the COVID-19 Pandemic on the time to diagnosis in pediatric patients with Primary central nervous system tumors

Primary central nervous system (CNS) tumors are a leading cause of death and disability amongst pediatric cancer patients. The early identification of symptom onset is critical in preventing diagnostic delays. In 2018, Akron Children’s Hospital published data on our response time to brain tumor diagnosis and launched educational programs in an effort to decrease diagnostic delays. The goal was to reduce the total diagnostic interval (TDI) in our patient population and reduce tumor- and treatment-related morbidities for these patients. Our post intervention group (2018-2021) was drastically affected by the numerous hospital changes secondary to the COVID-19 pandemic. We sought to examine the impact of COVID-19 related changes on TDI and attempted to identify groups at potential increased risk for diagnostic delays due to the unique pandemic constraints. A retrospective chart review was performed on patients at Akron Children’s Hospital to evaluate both for pre- (diagnosed Jan 1, 2018-February 29, 2020) and post-COVID-19 (diagnosed Mar 1, 2020-June 8, 2021) groups. Both subsets were evaluated statistically and were similar in all respects including demographics, symptomatology, tumor location, tumor type, and survival. The pre-COVID-19 group demonstrated a median TDI of 43.5 days, while the post-COVID-19 group demonstrated a 30-day median. The TDI for low-grade lesions increased from 32 to 59 days and for high-grade lesions decreased from 60 to 27.5 days in the post-pandemic cohort. Overall, this demonstrates a maintained average time to diagnosis for patients despite the pandemic restrictions in place. In addition, the differences in low vs. high-grade lesions suggest that tumors with a more subtle onset of symptoms were disproportionately affected, and highlight a population for intervention during the continued pandemic.

Can Neutrophil-Lymphocyte Ratio in Complete Blood Count Help in the Differential Diagnosis Between Acute Appendicitis and Right Ureteral Stones in Pediatric Age Groups?

Background and objectiveAbdominal pain is one of the most common problems in children presenting to the pediatric emergency departments and is often a diagnostic challenge for the physician. Clinical studies have been carried out on adult patients to differentiate between ureteral stones and acute appendicitis (AA) in which neutrophil-lymphocyte ratio (NLR) and platelet-lymphocyte ratio (PLR) were analyzed in the complete blood count, and it was found that NLR and PLR could help in the differential diagnosis. In this study, we investigated whether complete blood count parameters in pediatric patients could be helpful in the differential diagnosis between AA and right ureteral stones.MethodsThe files of pediatric patients who were followed up and treated for AA and right ureteral stones between January 2019 and March 2021 were reviewed retrospectively. The demographic characteristics of the patients and their WBC, NLR, PLR, and red cell distribution width (RDW) values were evaluated to determine whether there was a difference between the two groups.ResultsIn this study, 77 patients with AA and 48 patients with right ureteral stones were included. Univariate regression analysis revealed that age, gender, WBC, PLR, and NLR were factors likely responsible for AA. As per multivariate linear regression analysis, NLR level (odds ratio: 0.407; 95% CI: 0.293-0.566; p<0.001) was an independent predictor of AA.ConclusionBased on our findings, NLR can help in establishing the diagnosis in pediatric patients who present to the emergency department with right lower quadrant pain, and in whom physical examination, routine laboratory tests, and imaging methods cannot help distinguish between AA and ureteral stones.

Spontaneous perforation of common hepatic duct: an intraoperative surprise

BackgroundPediatric spontaneous bile duct perforation is one of the rare causes of acute abdomen in infants. With a highly variable presentation, diagnosis and treatment can prove challenging. We report a case of spontaneous common hepatic duct perforation mistaken for appendicular peritonitis.Case presentationAn otherwise healthy 3-year-old boy presented to the emergency department with complaints of abdominal pain, distention, bilious vomiting, and fever evolving for 4 days. Preoperative ultrasound was suggestive of appendicular peritonitis. Laparotomy revealed abundant biliary fluid, a distended gallbladder with thickened and inflammatory wall, and a macroscopically normal appendix. Intraoperative cholangiography showed a leak of contrast from the anterior wall of the common hepatic duct, 2–3 mm below the upper biliary confluence and 2 cm above the junction of the cystic duct to the common hepatic duct. A cholecystostomy was performed, and two external intraabdominal drains were placed. A retrograde cholangiogram was performed on postoperative day 21 showing no extravasation of contrast product. The patient was discharged on postoperative day 25.ConclusionSpontaneous perforation of the common hepatic duct is a rare phenomenon. It should be considered as a differential diagnosis in pediatric patients that present with unexplained peritonitis. The optimal method of diagnosis and management remains controversial.

Dentigerous cyst: a rapidly expanding swelling in a young patient

We present a case of a dentigerous cyst associated with an unerupted premolar tooth, and its surgical management in a 4-year-old child. Of note, 8 months prior to presentation, the patient was seen for extraction of multiple primary teeth under general anaesthesia. At the time of extraction, there were no signs of extra- or intra-oral mandibular swellings. Dentigerous cysts are one of the most common paediatric intra-osseous lesions. This case highlights the importance of taking a thorough dental history and the benefit of a multidisciplinary approach. This report also demonstrates the surgical management of this lesion, which included surgical excisional biopsy under general anaesthesia. CPD/Clinical Relevance: The reader should consider dentigerous cysts as a differential diagnosis in paediatric patients who present with dental swellings.

A Case of A 15-Year Old with Perforated Gallbladder Type II Secondary To Acute Acalculous Cholecystitis, Severe Secondary to Typhoid Fever with Bile Peritonitis, in Sepsis

Typhoid fever is one of the most common enteric fever in low to middle income countries. In the pediatric population, it is a rare cause of acalculous cholecystitis in which one of the dreaded complication is gall bladder perforation. This was a case of a 15-year-old male with 1-month history of intermittent undocumented fever, anorexia and weight loss. The patient presented with signs of pancytopenia and abdominal examination revealed acute abdomen. Patient was optimized and prepared for surgery. Intraoperative findings revealed Type II gall bladder perforation with bile peritonitis, and patient underwent exploratory laparotomy, cholecystectomy, lavage, Jackson-Pratt drain. The sepsis eventually resolved postoperatively, and the patient was discharged. Preoperative diagnosis in patients with gall bladder perforation is often challenging and sophisticated, due to its rarity. However, it should be considered as one of the differential diagnoses in pediatric patients presenting with atypical history of abdominal pain. At present, there are no specific guidelines in the management of complications such as gall bladder perforation in patients with typhoid fever. Therefore, early diagnosis and immediate surgical intervention of gall bladder perforation are of prime importance in the successful outcomes of these patients, given the high morbidity and mortality associated with this condition.

THE ROLE OF GENETICS IN THE UNDERSTANDING OF COMPLEX CONGENITAL HEART DISEASES

One of the most dynamic organs in the human body is the heart. Cardiac development is regulated by two key factors including signaling and transcriptional pathways. Thus, during the development of the fetus, any factor that disrupts the normal functioning of these factors may lead toward congenital heart defects (CHDs). Congenital heart disease is a complex multifactorial disease that involves both environmental and genetic factors.1,2 It is defined as any defect that occurs during heart development either in the cardiac structure or its associated vessels.3 Globally, it is one of the most common reasons for infant mortality and one of the most common birth defects in paediatric patients. As a rough estimate, 8 infants in every thousand live births are born with this fatal disease.4 Every year, in Pakistan approximately 40,000 children suffered from CHDs.5 Clinically depending upon the disease severity congenital heart diseases can be divided into two major subgroups one is non-syndromic and the other is syndromic. And among all these defects cardiac septation defects are the most common accounting for approximately 50% of the cases.6 It can be further sub-grouped as isolated lesions or complex diseases in combination with other heart defects.3 The exact mechanism involved in the pathogenesis of the congenital heart remains poorly understood but the most probable mechanism is multifactorial. Recent investigations suggest the role of epigenetic factors, micro RNA and small non-coding RNAs in the development of congenital heart defects. Moreover, advancements in molecular techniques including next-generation sequencing (NGS) helps in further detecting the genetic causes of CHDs such as the novel single nucleotide polymorphisms (SNPs) and copy number variants (CNVs).7 The current approaches used for genetic diagnosis of paediatric patients suffering from CHDs include karyotype analysis, copy number variation analysis, next-generation sequencing, and whole-genome or whole-exome sequencing. The targeted NGS relies on the selected region of know gene of interest and compared to whole genome or exome sequencing it provides us deeper gene coverage with easy variant detection at a lower cost. It provides robust detection of deletions, insertion and single nucleotide polymorphisms which chromosomal microarray analysis (CMA) and karyotyping cannot detect. To date, many pathogenic variants in different genes such as CITED2, CHD7, ZFPM2, MYH6 and KMT2D have been investigated by using targeted NGS. While whole-exome or genome sequencing help in the discovery of genes involves in the pathogenesis of congenital heart defects as it gives us more resolution at a single base-pair level. Thus accurate genetic diagnosis can be done by using the appropriate diagnostic techniques that can ultimately help in better patient counseling and clinical outcome.8 Furthermore, personalized medicines or finding mutations responsible for individual congenital heart disease patients can direct to better outcomes and approaches for each cardiac malformation phenotype. Thus, ultimately combined data of patients genotypic and phenotypic following well-designed guidelines will accelerate the translation of each SNP information into better treatment and clinical insights.9 Keywords: NGS, Single nucleotide polymorphisms, CHDs.

ÇOCUKLUK ÇAĞINDA VERTİGO: BAŞ DÖNMESİ OLAN ÇOCUKLARI NASIL DEĞERLENDİRELİM?

Objective&#x0D; Vertigo is a complaint consisting of wide spectrum&#x0D; of diagnoses in childhood. The aim of this study was&#x0D; to evaluate clinical characteristics and differential&#x0D; diagnosis of pediatric patients with vertigo.&#x0D; Material and Methods&#x0D; In this retrospective study, the medical records of&#x0D; a hundred patients who presented to the Pediatric&#x0D; Neurology Outpatient clinic with the complaint of&#x0D; vertigo between January 2018-January 2021 were&#x0D; reviewed. Patients were evaluated for age, gender,&#x0D; family history, duration of symptoms, frequency of&#x0D; attacks, provoking factors, accompanying symptoms,&#x0D; physical examination, laboratory findings and final&#x0D; diagnosis.&#x0D; Results&#x0D; The mean age was 12.39 years. The majority of the&#x0D; patients were males (64%). There were different&#x0D; causes of vertigo, but the most common two were&#x0D; infection (34%) and psychogenic vertigo (25%). The&#x0D; other frequent reasons were orthostatic hypotension&#x0D; (16%) and vitamin B12 deficiency (9%). Most of the&#x0D; patients had symptom duration for less than one&#x0D; month (46%), and the attacks were primarily seen&#x0D; (65%) every day. Patients explained their attacks as&#x0D; the motion of the surrounding (61%), spinning (27%),&#x0D; imbalance (20%), and others. The most common&#x0D; accompanying symptoms were fatigue (60%) and&#x0D; headache (54%). Laboratory data revealed vitamin&#x0D; B12 deficiency in nine patients; all other tests were&#x0D; in the normal range. Thirty-nine patients had cranial&#x0D; MRI, only 2 of them revealed abnormal findings, one&#x0D; of them was responsible for vertigo.&#x0D; Conclusion&#x0D; Vertigo in children creates a profound sense of&#x0D; anxiety both in parents and physicians leading to&#x0D; excessive number of functional testing and imaging&#x0D; examinations. Evaluation should begin with detailed&#x0D; history and comprehensive physical evaluation to&#x0D; avoid superfluous testing and diagnostics. Serious&#x0D; cases are fortunately rare and can be detected by&#x0D; careful clinical examination.

Saliva as a reliable sample for COVID-19 diagnosis in paediatric patients.

Saliva has been described a less invasive and easy to handle sample, compared to nasopharyngeal swabs (NPS), in the diagnosis of COVID-19 in adults. Although the advantages of using saliva is still more evident in paediatric patients, little is now about its sensitivity in this group. The aim of this study was to compare the performance of saliva to that of NPS in the detection of SARS-CoV-2 in paediatric patients with mild symptoms. This study evaluated saliva samples from children with suspected COVID-19 who attended public healthcare services of Araraquara, Sao Paulo, Brazil. Children were asked to spit into a sterile container for collection of about 1ml of saliva after the NPS collection. SARS-COV-2 detection was performed by using the Altona RealStar(R) SARS-CoV-2 RT-PCR Kit 1.0. The sample consisted of 50 patients, in which 27 were girls (54%) and 23 were boys (46%). Ten were positive for SARS-CoV-2 in at least one sample collected. The mean age was 10.24 {+/-} 3.52 years old and saliva was collected after 4.76 {+/-} 1.31 days from the symptoms. Saliva and NPS have showed the same performance in the SARS-CoV-2 detection (k = 0.865, P < 0.001). In conclusion, saliva is a reliable alternative sample for COVID-19 diagnosis in paediatric population.

Neutrophil-Lymphocyte Ratio as a Diagnosis Predictor in Pediatric COVID-19 Patients at Dr. OEN Kandang Sapi Hospital, Surakarta, Central Java, Indonesia

Background: COVID-19 is a global pandemic and affects all ages, even newborns. Until March 2021, there were 127 million cases of COVID-19 worldwide. In Indonesia, there were almost 1.5 million cases. The main symptoms of COVID-19 are fever and cough, simple laboratory tests such as measuring the neutrophil-lymphocyte ratio (NLR) are also included in the EWS (early warning score) so that they can be used to diagnose COVID-19 with a cut-off limit value of 3.13. The purpose of this study was to determine the value of NLR as a predictor of diagnosis in pediatric patients confirmed by RT-PCR Swab examination at Dr. Oen Kandang Sapi Hospital, Solo, Surakarta. Subjects and Method: A diagnostic test study that assessed the sensitivity, specificity, negative predictive value and positive predictive value of the NLR value as a predictor of COVID-19 diagnosis in pediatric patients confirmed by RT-PCR Swab examination at the time level of March 2020 - March 2021. Data were taken from electronic medical records of inpatients and sampling was done by consecutive admission sampling. Results: A total of 153 study subjects with 34 PCR (+) patients and 119 PCR (-) patients. The characteristics of the study sample were seen from gender, age, symptoms, chest x-ray and patient outcomes. The NLR cutoff limit value for pediatric COVID-19 patients is 1,625 with an AUC (area under curve) of 0.504. The NLR value of 1.625 has a sensitivity of 0.588 (58.8%) and a specificity of 0.513 (51.3%). The PPV (positive predictive value) was 0.256 (25.6%), the NPV (negative predictive value) was 0.813 (81.3%), the PPR (positive predictive ratio) was 1.207 and the NPR (negative predictive ratio) result was 0.803. Conclusion: The NLR cutoff value of 1,625 with a sensitivity of 58.8% cannot be used as a predictor of COVID-19 diagnosis in pediatric patients at Dr. Oen Kandang Sapi Hospital, Solo, Surakarta.

Diagnostic yield of clinical exome sequencing as a first-tier genetic test for the diagnosis of genetic disorders in pediatric patients: results from a referral center study.

The emergence of next-generation sequencing enabled a cost-effective and straightforward diagnostic approach to genetic disorders using clinical exome sequencing (CES) panels. We performed a retrospective observational study to assess the diagnostic yield of CES as a first-tier genetic test in 128 consecutive pediatric patients addressed to a referral center in the North-East of France for a suspected genetic disorder, mainly an inborn error of metabolism between January 2016 and August 2020. CES was performed using the TruSight One (4811 genes) or the TruSight One expanded (6699 genes) panel on an Illumina sequencing platform. The median age was 6.5years (IQR 2.0-12.0) with 43% of males (55/128), and the median disease duration was 7months (IQR 1-47). In the whole analysis, the CES diagnostic yield was 55% (70/128). The median test-to-report time was 5months (IQR 4-7). According to CES indications, the CES diagnostic yields were 81% (21/26) for hyperlipidemia, 75% (6/8) for osteogenesis imperfecta, 64% (25/39) for metabolic disorders, 39% (10/26) for neurological disorders, and 28% (8/29) for the subgroup of patients with miscellaneous conditions. Our results demonstrate the usefulness of a CES-based diagnosis as a first-tier genetic test to establish a molecular diagnosis in pediatric patients with a suspected genetic disorder with a median test-to-report time of 5months. It highlights the importance of a close interaction between the pediatrician with expertise in genetic disorders and the molecular medicine physician to optimize both CES indication and interpretation. Diagnostic yield of clinical exome sequencing (CES) as a first-tier genetic test for diagnosing genetic disorders in 128 consecutive pediatric patients referred to a reference center in the North-East of France for a suspected genetic disorder, mainly an inborn error of metabolism between January 2016 and August 2020. The CES diagnostic yields are reported in the whole population and patients' subgroups (hyperlipidemia, osteogenesis imperfecta, metabolic diseases, neurological disorders, miscellaneous conditions) (Icons made by Flaticon, flaticon.com; CC-BY-3.0).

Systemic diagnoses in pediatric patients undergoing cataract surgery

Systemic diagnoses in pediatric patients undergoing cataract surgery

Chest CT features of COVID-19 pediatric patients presented with upper respiratory symptoms

BackgroundAn outbreak of coronavirus disease 2019 (COVID-19) infection caused by a novel coronavirus began in December 2019 in Wuhan in central China that affect the children and adult and causes respiratory disease. This study aimed to highlight the CT features of pediatric patients with COVID-19 with upper respiratory symptoms.ResultsThe mean age of the 53 patients who enrolled in this study were 14.06 ± 4.12 years (range 1-18 years). Majority (75.5%) of them were adolescent. Running nose and fever were the most common symptoms. Forty-four (83%) patients had normal CT with no ground glass opacity (GGO) or consolidation, only 9 patients showed lung opacities; 5 cases showed consolidation, 2 cases with GGO, while consolidation with GGO was noted in another 2 patients. Among these 9 patient, six (66.7%) of them show unilateral lung opacities with peripheral distribution of these opacities in eight (88.9%) patients. The most frequently affected lobes were right and left lower lung lobes that were noted in 6 out of 9 patients with lung opacities (66.7%) in each lobe. Bronchitis was predominant in 23 (43.4%) cases.ConclusionsRT-PCR is a gold slandered test in the diagnosis of COVID-19 in children with upper respiratory tract symptoms as Chest CT cannot standalone as a diagnostic tool owing to high prevalence of normal chest CT in these patients. However, in case of lung affection, the presence of unilateral, peripheral consolidation with lower lobe predominance, in addition to bronchial wall thickening should be considered as a hallmark of chest CT in diagnosis of pediatric patients with COVID-19 with upper respiratory symptoms.

Early Ventricular Septal Defect Closure Prevents the Progression of Aortic Regurgitation: A Long-Term Follow-Up Study.

According to current short-term evidence, ventricular septal defect (VSD) closure should be performed as early as possible after aortic regurgitation (AR) diagnosis in pediatric patients to prevent AR progression. However, long-term follow-up data are lacking. Therefore, our aim was to evaluate the long-term follow-up (≥ 10years) of patients who underwent VSD closure as early as possible after AR diagnosis and to evaluate whether early VSD closure prevents progression of AR. This was a retrospective cohort study of 42 patients with VSD and AR who had undergone VSD closure at a median age of 2.9years, with a median waiting period from AR diagnosis to VSD closure of 3.4months and follow-up of a median 13.1years (interquartile range 10.0-15.8years). The preoperative degree of AR was trivial in 25 patients, mild in 15, and moderate in 2. Of the 33 patients followed up for ≥ 10years, none required aortic valve replacement and there was no incidence of mortality. The degree of AR improved or did not change, except in 1 patient. The size of the VSD (odds ratio [OR] 0.85; 95% confidence interval [CI] 0.62-1.18; p = 0.33), time from diagnosis to surgery (OR 1.00; 95% CI 1.000-1.001; p = 0.657), and age at the time of surgery (OR 1.00; 95% CI 0.998-1.004; p = 0.452) were not predictive of persistent postoperative AR. Therefore, VSD closure performed as early as possible after AR diagnosis could successfully prevent AR progression in patients with less than moderate preoperative AR, eliminating the need for aortic valve replacement and valvuloplasty.

Comparison of treatment effect and long-term outcomes for pediatric and adult Ewing sarcoma patients in British Columbia, Canada.

11531 Background: Treatment of Ewing Sarcoma (EWS) is challenging. While it is known to be sensitive to chemotherapy and radiation, the number of lines of therapy available are limited. This disease affects pediatric patients (PP) more often than adults (AP), and reported outcomes are worse for AP onset EWS in the literature. It is unclear if this is due to difference in the biology of disease in AP compared to PP, or if this is due to differences in treatment approach. Furthermore, optimal treatments and real world impact of treatment is unclear in both the PP and AP populations. This study identifies the features of therapy received by AP and PP with EWS in a large, mutli-institutional cohort, and provides real world evidence for the expected outcomes in both AP and PP with EWS. Methods: A cohort study analysis of the Sarcoma Outcomes Unit database at BC Cancer was conducted to identify patients diagnosed with EWS in British Columbia from January 1, 2000 to December 31, 2018. Data on the frequency, amount, and regimen of chemotherapy were collected. Baseline Charlson comorbidity index, age at diagnosis, progression free survival and overall survival were collected. Results: 108 patients with EWS were identified, 66 AP and 42 PP Median age at diagnosis for adults was 37 (19-86) and median age for diagnosis of pediatric patients was 14 (1-18). Real world median PFS and OS for AP were 23 mos and 79 mos, and for the PP were 32 mos and NE. Five year overall survival was 54% in AP and 77% in PP. Overall, there was no difference in the number of lines of therapy received between PP and AP, but the type of therapy was more dose-dense in the PP than in the AP, (85% vs 28% for dose dense chemo). 5 year overall survival was longer for PP who received dose dense regimens compared to non-dose dense regimens (HR 0.87), but was not different in the AP receiving dose dense regimens (HR 0.95), even when controlling for comorbidities. The most common chemotherapy regimen for AP was Vincristine, Adriamycin, cyclophosphamide alternating with Ifosfamide and Etoposide q3weeks, whereas in the pediatric population the most common chemotherapy regimen was the same but alternating q2weeks. Conclusions: The treatment plans for PP with EWS were more often dose dense compared to the AP. Outcomes for PP were vastly better than for APs, despite overall similarities in the number of lines of therapy and types of agents used. Given the lack of difference between dose dense and non-dose dense regimens for APs, this is not the likely cause of difference in survival between PPs and APs. Extrapolating pediatric protocols to the adult setting may not be appropriate given the differences in outcomes. Further work to identify effective therapies and predictive biomarkers in this disease are needed, and my further identify reasons for discrepant outcomes in pediatric and adult populations.

Pectus carinatum as the key to early diagnosis of Morquio A syndrome: a case report

BackgroundA 20-month-old Asian boy with normal growth presented with genu valgum, kyphosis, and pectus carinatum, with no neurological symptoms. No other symptoms suggestive of mucopolysaccharidoses, for example joint contracture and peculiar facies, were present.Case presentationAs part of our differential diagnosis we found elevated urine glycosaminoglycans, which triggered further investigation. Detailed examination showed flattening of the ribs, kyphoscoliosis and ovalization of the thoracolumbar vertebral body, strikingly short metacarpals, and very slight cardiac regurgitation. N-Acetylgalactosamine-6-sulfatase levels in the blood and dermal fibroblasts were very low, thus confirming diagnosis of Morquio A within 2 months of presentation. The patient was placed on elosulfase alfa enzyme replacement therapy and followed for 3 years.ConclusionsThis case exemplifies the importance of considering mucopolysaccharidoses as part of the initial differential diagnosis of pediatric patients with skeletal deformities; urine glycosaminoglycan levels and a blood enzyme mucopolysaccharidoses panel are simple screening tests that could lead to early definitive diagnosis.

Influence of body mass index at diagnosis on outcome of thyroid cancer in children and adolescents

PurposeTo systemically examine the relationship between body mass index, the extent of thyroid cancer and metastatic burden at diagnosis, and overall outcomes in children and adolescents with thyroid cancer. MethodsA retrospective series of children and adolescents with differentiated thyroid cancer who underwent total thyroidectomy and 131I therapy was analyzed. Body mass index (BMI) at the time of surgery was assessed. The Chinese age- and sex-specific BMI percentile criteria for screening overweight and obesity in children and adolescents were used to define the overweight and obesity among patients. The relationship between BMI and clinicopathological features and clinical outcomes of the disease was evaluated by logistic regression modeling, incorporating the eighth edition of the American Joint Committee on Cancer TNM staging system and the 2015 American Thyroid Association guidelines. ResultsThis study included 181 children and adolescents with differentiated thyroid cancer (82.9% females, median age 17 years). The mean BMI was 21.0 ± 3.9 kg/m2; 77.9% of the patients (N = 141) were normal weight, 13.2% (N = 24) were overweight, and 8.8% (N = 16) were obese. No positive associations were noted between BMI and T, N, or M stage on logistic regression analyses. The absence of an association was also demonstrated on analysis by BMI categories. After a median follow-up of 51 months, 114 children and adolescents (63.0%) had achieved excellent response to therapy. No associations were noted for persistent/recurrent disease among BMI groups. ConclusionOur study highlights the absence of increased disease burden at the time of thyroid cancer diagnosis in pediatric patients with high BMI along with the same prognosis compared with normal-weight pediatric patients.

Specialty-Specific Diagnoses in Pediatric Patients With Postconcussion Syndrome: Experience From a Multidisciplinary Concussion Clinic.

Objective:To describe the collaborative findings across a broad array of subspecialties in children and adolescents with postconcussion syndrome (PCS) in a pediatric multidisciplinary concussion clinic (MDCC) setting.Design:Retrospective analysis.Setting:Multidisciplinary concussion clinic at a pediatric tertiary-level hospital.Patients:Fifty-seven patients seen in MDCC for evaluation and management of PCS between June 2014 and January 2016.Interventions:Clinical evaluation by neurology, sports medicine, otolaryngology, optometry, ophthalmology, physical therapy, and psychology.Main Outcome Measures:Specialty-specific clinical findings and specific, treatable diagnoses relevant to PCS symptoms.Results:A wide variety of treatable, specialty-specific diagnoses were identified as potential contributing factors to patients' postconcussion symptoms. The most common treatable diagnoses included binocular vision dysfunction (76%), anxiety, (57.7%), depression (44.2%), new or change in refractive error (21.7%), myofascial pain syndrome (19.2%), and benign paroxysmal positional vertigo (17.5%).Conclusions:Patients seen in a MDCC setting receive a high number of treatable diagnoses that are potentially related to patients' PCS symptoms. The MDCC approach may (1) increase access to interventions for PCS-related impairments, such as visual rehabilitation, physical therapy, and psychological counseling; (2) provide patients with coordinated medical care across specialties; and (3) hasten recovery from PCS.