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Abstract Background: Individuals with type 2 diabetes who have optimum condition management are exposed to a significantly higher risk of developing cardiovascular disease (CVD) compared to those who do not have diabetes. People with diabetes are estimated to have a fourfold greater risk of developing CVD than people without diabetes. CVD risk factors other than diabetes include older age, obesity hypertension, dyslipidemia, smoking, and a family history of coronary or kidney diseases. Objectives: The study aims to assess the cardiovascular risk factors among type2 diabetes at Ribat Hospital Diabetes Clinic, Sudan. Methods: T2 DM patients were evaluated for the presence of CVD risk factors by using data collecting form to extract data verbally and from patients' files. Results: Out of 147 T2 DM files, 92 (61.7 %) were female, 57 (38.3 %) were male, and 58 (38.9 %) patients were ≥ 60 year old. Patients who had poor glycemic control were 112 (75.2 %) and those who met the glycemic target were only 37 (24.8 %). Older age (P = 0.01) and diabetes duration (P = 0.026) were associated with poor glycemic control. Prevalence of hypertension was 61 (40.9 %), dyslipidemia 31 (20.8 %), and physical inactivity 112 (75.2 %). All patients had at least one CVD risk factor and those having all three risk factors were 48 (32.2 %). Conclusion: All T2 DM diabetic patients in RHDC had at least one CVD risk factor and almost a third of them had all three risk factors. Poor glycemic control, physical inactivity, hypertension, and age ≥ 60 had the higher prevalence of CVD risk factors.

Objectives: To assess the hysteroscopic value in the management of intrauterine lesion in women with recurrent pregnancy loss.Methods: This study was done in Ain Shams Maternity Hospital after the approval of the research Ethics Committee, during the period between August 2014 and December 2015 where 200 nonpregnant women with a history of three or more consecutive unexplained first and second trimester miscarriages before 20 weeks were recruited from recurrent miscarriage clinic. A written informed consent was obtained from all women before participation.Results: This current study was conducted in Ain Shams University Maternity Hospital during the period between August 2014 to May 2015 a total of 200 women with history of recurrent miscarriage were included in the study. Regarding the results of this study the mean age was 30.5(5.7), the mean number of previous abortion 3(3-5) the mean number of the first trimesteric abortion was 2 with range (2-2) the mean number of second trimesteric abortion was 2 with range (1-2). In this study, 88% of patients were nullipara. It was also found that hysteroscopic findings were found in 58.5%. Uterine anomalies was present in 21%, including septate uterus and intrauterine adhesion (IUAs) were present in 12.5%. Endometrial polyps were present in 8.5%, bicornute uterus in 4.5%, unicornuate uterus in 4.5% while submucous myomas were present in 7.5%. It was found that 48.5% need hysteroscopic intervention including 21% need septectomy 12.5% need adhesiolysis, 6.5% need myomectomy while 8.5% need polypectomy. The study found that no statistically significant difference between patients with normal hysteroscopic finding and patients with abnormal hysteroscopic finding as regard age, time of previous abortion and number of previous abortion. But there was statistically significant difference as regard number of previous delivery and abnormal HSG.Conclusions: It appears that hysteroscopy is a useful tool in the diagnosis and treatment of the causes of recurrent miscarriage that can be performed safely without anesthesia in most cases. The prevalence of uterine anomalies in patients with recurrent miscarriages is 54.5%, septate uterus is the most common anomaly and for this reason uterine anomalies should be systematically assessed in patients with recurrent miscarriage. [ABSTRACT FROM AUTHOR]

Abstract Background Using probiotics have become popular. They are considered an alternative to Antibiotic Growth Promoters (AGP). Probiotics are supplemented into animal feed for improving growth performance along with preventing and controlling enteric pathogens. The aim of this work was to study the impact of dietary supplementation of Mannan-oligosaccharide and β-Glucan (Agrimos®) on broiler challenged with Escherichia coli O78 (E. coli O78 - marked with an antibiotic (320 μg ciprofloxacin/ml broth) on growth performance, serum biochemistry, immune organs-histopathology, E-coli colonization, and hepatic transcripts of Tumor necrosis factor-alpha (TNF-α) and Nuclear factor-kappa B (NF-ϰB). A total of 125 one-day-old chicks were used for conducting the experiment. Five one-day-old chicks were slaughtered for measuring the initial weight of the lymphoid tissue. The remaining chicks (120) were allotted into four groups according to Mannan-oligosaccharide and β-Glucan supplementation, and E. coli infection. The data were analyzed using SPSS version 16. Results Results indicated significant alteration of growth performance, serum biochemistry, and selected liver gene expression with pathological lesions, especially in the lymphoid organs due to E. coli infection. These alterations were mitigated by Mannan-oligosaccharide and β-Glucan supplementation. Conclusion It could be concluded, Mannan-oligosaccharide and β-Glucan supplementation in broiler’s diet improved the immune response of broilers and mitigated pathological lesion resulted from E. coli infection.

Background. The frequent expansion of the energy drinks (EDs) market has caused an extensive increase in the consumption of EDs, especially among younger populations. However, the lack of knowledge on EDs and their perceived beneficial effects could lead to excessive EDs consumption, which is strongly associated with serious side effects. This study aimed to assess the knowledge and perceived beneficial effects of EDs consumers and determine the consumption patterns and side effects experienced by different EDs consumers among the Malaysian population. Methods. A descriptive cross-sectional study was conducted in Malaysia from February to April 2021. A structured and validated questionnaire, consisting of 5 sections with 46 items, was distributed online. Only 515 out of 591 invited participants agreed to participate in the study. Descriptive and inferential analysis were done using SPSS. Results. The median age of participants was 23 ± 7.3 years. The majority of participants (65%) were unaware of the active ingredients of EDs, and approximately 40% of them had no idea that EDs contain caffeine. The main reason for consuming EDs was to stay awake (43%), and Red Bull was the most preferred brand (57%). Lack of rest (57%), headache (53%), and nervousness (49%) were the most experienced side effects. A significant difference was observed between consumption patterns and knowledge and perceived beneficial effects (p

High-fidelity clinical simulation is currently a well-established teaching tool. However, high-fidelity representations of patients in critical conditions have the potential to elicit emotions among learners and impact their cognitive load (CL). Teaching with clinical simulation may induce both emotional and cognitive overloads. The relationship between anxiety and CL during clinical simulation was studied. Forty-one undergraduate medical students participated in this study; 19 males and 22 females. The state-anxiety component of State-Trait Anxiety Inventory was administered during clinical simulation teaching sessions at time points: pre-scenario, post-scenario and post-debriefing. The Cognitive Load Scale (Leppink et al.) questionnaire was also completed post-scenario. This assessed the three components of CL: intrinsic cognitive load (ICL), extraneous cognitive load (ECL) and self-perceived learning (SPL). Median CL scores for ICL, ECL and SPL were compared between groups of low-anxiety and high-anxiety participants using a Mann-Whitney U test. State-anxiety scores were high for both the pre-scenario and post-scenario time points with a significant reduction following post-debriefing. The median (interquartile range) state-anxiety scores were 41.0 (33.0–50.0), 46.0 (33.0–52.0) and 31.0 (23.0–39.0) for the pre-scenario, post-scenario and post-debriefing time points respectively. Students with high state-anxiety had higher ECL scores (median = 2.0) than students with low state-anxiety (median = 0.9) at the post scenario time point (U = 220, p = 0.043). No statistical relation was seen with state-anxiety for either ICL or SPL. State-anxiety immediately after the simulation scenario is associated with ECL but not ICL or SPL.

It had previously been suggested that the submandibular gland (SMG) of mice and rats may contain in vivo immunosuppressive factors(s). To identify such factor(s), we used a multi-step purification procedure of rat SMG extracts. Gel filtration chromatography of the SMG crude extract resulted in two pools of fractions with significant effects on lymphocyte reactivity in the in vitro concanavalin A (Con A) bioassay. Of these two pools, only the one with lower molecular weight resulted in the prolongation of murine skin allograft survival, the suppression of the delayed-type hypersensitivity (DTH) response to picryl chloride and the decrease in number of direct (IgM) plaque-forming cells against sheep red blood cells. Fractionation of this low molecular weight (LMW) pool through hydrophobic interaction chromatography resulted in three protein fractions designated A, B and C. Of these fractions only fraction A produced significant suppression of the DTH response. Further purification of fraction A with anion exchange chromatography produced two fractions with immunosuppressive activity in the DTH response. One fraction demonstrated on SDS-PAGE a single component of 40,000 MW, while the other had two components of 30,000 and 40,000 MW respectively. [ABSTRACT FROM AUTHOR]

Objectives: The literature lacks comprehensive evidence on the efficacy of advanced platelet rich fibrin(A-PRF) in treating gingival recession. Therefore, this systematic review and meta-analysis aimed to evaluate the effectiveness of A-PRF in the treatment of gingival recession., Materials and Methods: We adhered to the guidelines of PRISMA in searching the following databases: PubMed/MEDLINE, Embase, Cochrane Library, Web of Science, and Scopus to include all the eligible studies according to the prespecified inclusion and exclusion criteria. We conducted our search up to February 28, 2024. We conducted a meta-analysis of the primary and secondary clinical outcomes to measure the changes from baseline to 6 months after surgery., Results: Our review included 10 randomized clinical trials in which 146 participants with 457 recession defects were included. We found that combination of A-PRF with various surgical techniques, such as coronally advanced flap (CAF) connective tissue graft (CTG), VISTA, tunneling, and pinhole surgical technique, demonstrated promising outcomes but varied by comparison group. We observed that CTG with CAF showed a higher reduction in recession depth in comparison to A-PRF with CAF. This review indicated no statistical or clinical differences in recession width, width of keratinized gingiva, probing depth, and clinical attachment level between the study and control groups., Conclusions: Due to the less invasive nature of A-PRF, it provides a better clinical option to improve the outcomes of treating gingival recession. However, more well-designed RCTs with standardized approaches are needed to confirm these results., Competing Interests: Declarations Ethics approval Ethical approval was not applicable for this systematic review. Informed consent Informed consent was not applicable for this systematic review. Consent for publication Not Applicable. Conflict of interest The authors declare no conflict of interest in connection with this study., (© 2024. The Author(s).)

Background: Stroke in young patients results in disproportionately high societal cost given the productive life-years lost. Little is known about stroke in young Egyptian patients. We aimed to analyze clinicodemographic characteristics, functional outcome, and socioeconomic impact of ischemic stroke among young Egyptian adults., Methods: This is a prospective, observational cohort study of consecutively recruited patients with acute ischemic stroke (AIS), 18-50 years, between September 2022 and September 2023 at a tertiary stroke center in the south of Egypt. We recorded baseline demographic and cardiovascular risk factors, stroke severity, stroke subtype according to the TOAST classification, intravenous thrombolysis, employment, and ambulation status pre- and post-stroke, post-stroke complications, and 90-day functional outcome measured by the modified Rankin Scale (mRS)., Results: Our cohort comprised 210 patients, 38.0 (±7.8) years, 89 (42%) females. Mean NIHSS score was 11.2 (±4.8); in-hospital case fatality was 9% (19 patients). Dyslipidemia (n = 105, 50%), smoking (n = 105, 50%), and hypertension (n = 67, 32%) were the most prevalent cardiovascular risk factors. At 90 days, 58 (29%) patients had a 90-day mRS 0-1 and 53 (26%) met criteria for depression diagnosis. Sixty-nine of the 116 employed individuals (59%) remained out of work after 90 days of stroke, 61 of whom were single earners in their household. 36/60 (60%) thrombolysis-eligible patients received it; an additional 98 otherwise thrombolysis-eligible patients presented >4.5 h from symptom onset. Patients receiving IV thrombolysis were significantly more likely to have resumed full-time work at 90 days (32% vs. 11%, p = 0.006) but with no significant difference in 90-day mRS., Conclusions: Young adult AIS patients in Egypt experience high rates of post-stroke depression and face challenges in their ability to work and provide for their families. Since most patients have treatable cardiovascular risk factors and only about two-thirds of eligible patients receive thrombolysis, reinforcing primary prevention, education about early stroke signs, and benefits of acute can improve outcomes and have significant potential societal benefit., (© 2024 S. Karger AG, Basel.)

We conducted integrative somatic-germline analyses by deeply sequencing 864 cancer-associated genes, complete genomes and transcriptomes for 300 mostly previously treated children and adolescents/young adults with cancer of poor prognosis or with rare tumors enrolled in the SickKids Cancer Sequencing (KiCS) program. Clinically actionable variants were identified in 56% of patients. Improved diagnostic accuracy led to modified management in a subset. Therapeutically targetable variants (54% of patients) were of unanticipated timing and type, with over 20% derived from the germline. Corroborating mutational signatures (SBS3/BRCAness) in patients with germline homologous recombination defects demonstrates the potential utility of PARP inhibitors. Mutational burden was significantly elevated in 9% of patients. Sequential sampling identified changes in therapeutically targetable drivers in over one-third of patients, suggesting benefit from rebiopsy for genomic analysis at the time of relapse. Comprehensive cancer genomic profiling is useful at multiple points in the care trajectory for children and adolescents/young adults with cancer, supporting its integration into early clinical management., (© 2022. The Author(s).)

Background: Chronic telogen effluvium is characterised by diffuse loss of hair of the scalp. One of the emerging lines of treatment is platelet-rich plasma. However, not much of published data exist., Aims: A pilot study was conducted on chronic telogen effluvium patients to evaluate the efficacy and safety of platelet-rich plasma, and to compare two different methods of platelet-rich plasma preparation., Methods: The study included 30 female patients with chronic telogen effluvium. Patients were randomised into three groups: Group (1): Special platelet-rich plasma tubes centrifuged at 3500 rpm; Group (2): Ordinary laboratory tubes centrifuged at 1000 rpm; Group (3): Normal saline as a placebo. Patients' evaluation was done with visual analog scale, hair pull test, trichoscopy, photos, satisfaction questionnaire, and safety. All patients received four monthly sessions. Patients were evaluated one month and three months after the last session., Results: The hair pull test,visual analogue scale, and patient satisfaction results showed a statistically significant difference between group 1 vs. group 3 and group 2 vs.group 3 at one and three months after the sessions, while there was no difference between group1 vs. group 2. Trichoscopy results (baseline, one and three months after treatment) showed a significant increase in hair density and thickness in the frontal area, temporal area, and the vertex in groups 1 and 2 only. There was no statistically significant difference between the three groups with regards to side effects., Limitations: The sample size was small with ten patients in each group. Furthermore, the follow-up of patients was for only three months., Conclusions: Platelet-rich plasma could be considered as a promising therapy for patients with chronic telogen effluvium with an excellent safety profile. The ordinary laboratory low-cost tubes might be a reliable alternative to the expensive special platelet-rich plasma kits tubes. The trial registry number is PACTR202006539654415.

High-fidelity clinical simulation is currently a well-established teaching tool. However, high-fidelity representations of patients in critical conditions have the potential to elicit emotions among learners and impact their cognitive load (CL). Teaching with clinical simulation may induce both emotional and cognitive overloads. The relationship between anxiety and CL during clinical simulation was studied. Forty-one undergraduate medical students participated in this study; 19 males and 22 females. The state-anxiety component of State-Trait Anxiety Inventory was administered during clinical simulation teaching sessions at time points: pre-scenario, post-scenario and post-debriefing. The Cognitive Load Scale (Leppink et al.) questionnaire was also completed post-scenario. This assessed the three components of CL: intrinsic cognitive load (ICL), extraneous cognitive load (ECL) and self-perceived learning (SPL). Median CL scores for ICL, ECL and SPL were compared between groups of low-anxiety and high-anxiety participants using a Mann-Whitney U test. State-anxiety scores were high for both the pre-scenario and post-scenario time points with a significant reduction following post-debriefing. The median (interquartile range) state-anxiety scores were 41.0 (33.0-50.0), 46.0 (33.0-52.0) and 31.0 (23.0-39.0) for the pre-scenario, post-scenario and post-debriefing time points respectively. Students with high state-anxiety had higher ECL scores (median = 2.0) than students with low state-anxiety (median = 0.9) at the post scenario time point (U = 220, p = 0.043). No statistical relation was seen with state-anxiety for either ICL or SPL. State-anxiety immediately after the simulation scenario is associated with ECL but not ICL or SPL.

Introduction: Clinicians and healthcare professionals rely heavily on health-associated standards, such as reference intervals (RIs), for appropriate laboratory test result interpretation. RIs are commonly partitioned into discrete age/sex bins based on statistical and/or clinical significance. In pediatric hematology, such partitioning does not adequately represent complex variation in analyte concentrations throughout maturation. The objective of this study was to establish continuous RIs for common hematological parameters in the healthy pediatric Canadian Laboratory Initiative on Pediatric Reference Intervals (CALIPER) cohort., Methods: Data from healthy CALIPER children and adolescents (6 months-<19 years) were used to generate continuous RIs (ie, 2.5th and 97.5th quantiles) for 19 hematological parameters. Continuous curves were statistically established with nonparametric quantile regressions. Flagging rate analysis was completed for the established continuous upper and lower reference limits and subsequently compared to previously published discrete CALIPER reference intervals for all parameters., Results: Continuous RIs were established for 19 hematology parameters, where seven required sex-specific reference curves. Based on flagging rate assessment, continuous RIs appear to more accurately estimate hematological reference limits over the pediatric age range, especially for analytes with complex age- and sex-specific reference value patterns., Conclusions: This is the first study to generate continuous RIs for a breadth of hematological markers in a healthy pediatric Canadian population. The increased power of continuous reference intervals to accurately estimate the complex relationship between hematological analyte concentration and age during a time of extensive growth and development is expected to improve laboratory test result interpretation and, subsequently, pediatric clinical decision-making., (© 2021 John Wiley & Sons Ltd.)

Objective: Macrophage activation syndrome (MAS), a life-threatening inflammatory complication, is increasingly recognized in childhood-onset systemic lupus erythematosus (cSLE). It can be a challenge to differentiate active cSLE from MAS. We generated decision rules for discriminating MAS from active cSLE in newly diagnosed patients., Methods: We conducted a retrospective cohort study of consecutive, newly diagnosed, active cSLE patients with fever, requiring hospital admission to The Hospital for Sick Children from January 2003 to December 2007 (cohort 1) and January 2008 to December 2013 (cohort 2). All patients met ≥ 4 American College of Rheumatology or Systemic Lupus International Collaborating Clinics criteria, and were steroid-naïve and infection-free. MAS was diagnosed based on expert opinion. Recursive partitioning was applied to each cohort to derive a decision rule based on clinical and laboratory features, distinguishing MAS from non-MAS cSLE. Each decision rule was applied to the alternate, independent cohort. Sensitivity and specificity of these decision rules were compared to existing criteria., Results: Cohort 1 (n = 34) and cohort 2 (n = 41) each had 10 patients with MAS. Recursive partitioning in cohort 1 identified ferritin ≥ 699 μg/L as the sole best discriminator between MAS and non-MAS patients (R 2 = 0.48), and in cohort 2, ferritin ≥ 1107 μg/L was the best discriminator for MAS, followed by lymphocytes < 0.72 × 10 3 /mm 3 (R 2 = 0.52). Cross-validation of our decision rules maintained 90-100% sensitivity and 65-85% specificity., Conclusion: Our decision rule demonstrated improved performance compared to preliminary guidelines for MAS in cSLE from the Lupus Working Group of the Paediatric Rheumatology European Society and familial hemophagocytic lymphohistiocytosis diagnostic criteria. Validation in independent cohorts is required., (© 2021 by the Journal of Rheumatology.)

Children with Down syndrome have a 150-fold increased risk of developing myeloid leukemia, but the mechanism of predisposition is unclear. Because Down syndrome leukemogenesis initiates during fetal development, we characterized the cellular and developmental context of preleukemic initiation and leukemic progression using gene editing in human disomic and trisomic fetal hematopoietic cells and xenotransplantation. GATA binding protein 1 ( GATA1 ) mutations caused transient preleukemia when introduced into trisomy 21 long-term hematopoietic stem cells, where a subset of chromosome 21 microRNAs affected predisposition to preleukemia. By contrast, progression to leukemia was independent of trisomy 21 and originated in various stem and progenitor cells through additional mutations in cohesin genes. CD117 + /KIT proto-oncogene (KIT) cells mediated the propagation of preleukemia and leukemia, and KIT inhibition targeted preleukemic stem cells., (Copyright © 2021 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works.)

Objective: To establish reference intervals for hemoglobin and mean corpuscular volume (MCV) in an ethnically diverse community sample of Canadian children 36 months and younger., Methods: We collected blood samples from young children at scheduled primary care health supervision visits at 2 weeks, 2, 4, 6, 9, 12, 15, 18, 24, and 36 months of age. Samples were analyzed on the Sysmex XN-9000 Hematology Analyzer. We followed the Clinical and Laboratory Standards Institute guidelines in our analysis. Data were partitioned by sex and also combined. We considered large age partitions (3 and 6 months) as well as monthly partitions. Reference intervals (lower and upper limits) and 90% confidence intervals were calculated., Results: Data from 2106 children were included. The age range was 2 weeks to 36 months, 46% were female, 48% were European and 23% were of mixed ethnicity. For hemoglobin, from 2 to 36 months of age, we found a wide reference interval and the 90% confidence intervals indicated little difference across age groups or according to sex. For MCV, from 2 to 7 months of age there was considerable decrease in the reference interval, which was lowest during the second year of life, followed by a slight increase in the last months of the third year of life., Conclusion: These findings suggest adoption of a single hemoglobin reference interval for children 2-36 months of age. Further studies in children under 4 months of age are needed., Trial Registration: TARGet Kids! cohort is registered at ClinicalTrials.gov. www.clinicaltrials.gov . Identifier: NCT01869530 .

Background: Primary presentation of Hodgkin lymphoma (HL) with bone and/or bone marrow involvement is a rare entity. Diagnostic criteria, treatment approaches, and follow-up strategies for these patients have not been standardized., Observation: We report a unique case of bone and bone marrow HL in an adolescent male without lymph node involvement., Conclusions: It is important to keep HL in the differential diagnosis of isolated and multifocal bone lesions. Evidence is needed to define the best management of these patients.

Introduction: Hematology laboratory parameters are among the most routinely ordered tests in support of adult and pediatric care. However, appropriate interpretation of test results has been a challenge in pediatrics since accurate and up-to-date reference intervals that reflect the dynamic physiological changes associated with growth and development have not been available. Critical gaps continue to exist in pediatric hematology reference intervals for modern laboratory platforms. To address this gap, this study establishes age- and sex-specific reference intervals for 25 hematology parameters in the CALIPER cohort of healthy children and adolescents using a common platform, the Sysmex XN-3000 analytical system., Methods: Fresh whole blood samples collected from a total of 641 healthy children and adolescents (birth to <21 years) with informed consent were analyzed for 25 hematological parameters on the Sysmex XN-3000 Hematology Analyzer. Age- and sex-specific reference standards were calculated based on Clinical and Laboratory Standards Institute guidelines., Results: Of the 25 analytes assessed, 19 required age-partitioning and seven required sex-partitioning (ie, red blood cell count, hemoglobin, hematocrit, mean corpuscular volume, red blood cell distribution width-SD, red blood cell distribution width-CV, and monocyte percentage). Age- and sex-specific differences mostly coincided with the onset of puberty., Conclusion: This study establishes a comprehensive database of pediatric reference intervals for hematology parameters in the CALIPER cohort using the widely used Sysmex XN-3000 analytical platform. These data highlight the dynamic hematological profile observed in healthy children and adolescents and the need for reference interval stratification by age and sex., (© 2020 John Wiley & Sons Ltd.)

Mutations in SH2D1A, encoding the intracellular adaptor signaling lymphocyte activation molecule associated protein (SAP), are associated with X-linked lymphoproliferative disease type 1 (XLP1). We identified a novel hemizygous SH2D1A c.49G > A (p.E17K) variant in a 21-year-old patient with fatal Epstein-Barr virus infection-associated hemophagocytic lymphohistiocytosis. Cellular and biochemical assays revealed normal expression of the SAP variant protein, yet binding to phosphorylated CD244 receptor was reduced by >95%. Three healthy brothers carried the SH2D1A c.49G > A variant. Thus, data suggest that this variant represents a pathogenic mutation, but with variable expressivity. Importantly, our results highlight challenges in the clinical interpretation of SH2D1A variants and caution in using functional flow cytometry assays for the diagnosis of XLP1., (© 2020 The Authors. Pediatric Blood & Cancer published by Wiley Periodicals, Inc.)

Chromosomal rearrangements resulting in fusion transcripts have been reported in precursor B-cell acute lymphoblastic leukemia (B-ALL). The identification of fusion events is crucial in the diagnosis of B-ALL. In this study, we used NanoString nCounter technology to design, validate, and evaluate a multiplex panel for the detection of B-ALL fusion transcripts. Fifty-one B-ALL fusion transcripts reported in children in the literature were included in the design of the NanoString panel. Twenty-six fusion transcripts were validated using 64 positive-control samples and 74 negative-control samples with 100% sensitivity and 99% specificity in comparison to RT-PCR. Our results support a potential role of NanoString's technology as a robust and cost-effective technique that could be used in the detection of fusion transcripts and implemented into the diagnostic algorithm of B-ALL., (Copyright © 2020 American Society for Investigative Pathology and the Association for Molecular Pathology. Published by Elsevier Inc. All rights reserved.)

Diagnostic procedures in children with acute lymphoblastic leukemia (ALL) are typically performed under general anesthesia. Anticipation of the diagnosis based on findings in peripheral blood allows scheduling of the first dose of intrathecal chemotherapy and diagnostic bone marrow (BM) aspirate during a single anesthetic. We retrospectively compared paired results of peripheral blood (PB) flow cytometric analysis and BM evaluation in 383 children with ALL diagnosed consecutively at a single center and found very high concordance of results between both tests. We conclude that PB flow cytometry may help streamline planning of procedure-related anesthetics during diagnosis and early treatment of childhood ALL., (© 2017 Wiley Periodicals, Inc.)

Background: ZNF384 gene rearrangements with multiple partner genes are recurrent in acute leukemia and are most often associated with a precursor B cell immunophenotype. The overall incidence of this genetic category of leukemia is uncertain., Procedure: Patients with ZNF384 gene rearrangements from a cohort of 240 precursor B cell acute lymphoblastic leukemia (ALL) pediatric patients over a 3.5-year time period were characterized with detailed cytogenetic, FISH, genomic, and clinical analyses., Results: Seven of the 240 patients were identified to have ZNF384 gene rearrangements including partner genes TCF3 (four patients), EWSR1 (one patient), EP300 (one patient), and the novel gene partner ARID1B (one patient). The translocations were confirmed by FISH analysis and with RNA sequencing for the EP300 and ARID1B partner genes. Genomic microarray analysis showed an average of 2.7 copy number alterations in each case with no evidence of imbalance at the translocation breakpoints. Six of the patients with ZNF384 gene rearrangements had precursor B cell ALL with a CD10- immunophenotype and myeloid-associated antigens. One of the patients also had myeloperoxidase expression and was diagnosed as mixed phenotype B/myeloid acute leukemia. None of the patients have relapsed with event-free survival ranging from 6 years 2 months to 9 years 2 months., Conclusions: This study suggests that the frequency of ZNF384 gene rearrangement in pediatric precursor B cell ALL is approximately 3%. The ARID1B gene, commonly mutated in multiple types of cancer, was identified as an additional ZNF384 gene fusion partner., (© 2016 Wiley Periodicals, Inc.)

Primary effusion lymphoma (PEL) is a rare lymphoma that occurs more frequently in immunocompromised adults and has a poor survival. We report a 9-year-old female with combined immunodeficiency with an Epstein-Barr virus positive/human herpes virus 8 negative PEL-like lymphoma. The treatment with systemic chemotherapy for non-Hodgkin lymphoma, zidovudine, and interferon-α failed to control disease progression. This is the first reported pediatric case of PEL-like lymphoma. Increased diagnostic awareness and more effective treatment strategies are needed for this rare lymphoma., (© 2016 Wiley Periodicals, Inc.)

Background: In a collaboration between the Canadian Laboratory Initiative on Pediatric Reference Intervals (CALIPER) and the Canadian Health Measures Survey (CHMS), we determined reference value distributions using an a priori approach and created a comprehensive database of age- and sex-stratified reference intervals for clinically relevant hematologic parameters in a large household population of children and adults., Methods: The CHMS collected data and blood samples from 11 999 respondents aged 3-79 years. Hematology markers were measured with either the Beckman Coulter HmX or Siemens Sysmex CA-500 Series analyzers. After applying exclusion criteria and removing outliers, we determined statistically relevant age and sex partitions and calculated reference intervals, including 90% CIs, according to CSLI C28-A3 guidelines., Results: Hematology marker values showed dynamic changes from childhood into adulthood as well as between sexes, necessitating distinct partitions throughout life. Most age partitions were necessary during childhood, reflecting the hematologic changes that occur during growth and development. Hemoglobin, red blood cell count, hematocrit, and indices (mean corpuscular volume, mean corpuscular hemoglobin, and mean corpuscular hemoglobin concentration) increased with age, but females had lower hemoglobin and hematocrit starting at puberty. Platelet count gradually decreased with age and required multiple sex partitions during adolescence and adulthood. White blood cell count remained relatively constant over life, whereas fibrinogen increased slightly, requiring distinct age and sex partitions., Conclusions: The robust dataset generated in this study has allowed observation of dynamic biological profiles of several hematology markers and the establishment of comprehensive age- and sex-specific reference intervals that may contribute to accurate monitoring of pediatric, adult, and geriatric patients., (© 2015 American Association for Clinical Chemistry.)

FMS-like tyrosine kinase 3 (FLT3) internal tandem duplication (ITD) is a somatic mutation associated with poor outcome when treated with chemotherapy alone. In children, hematopoietic stem cell transplantation (HSCT) is recommended, but very limited data on outcome are reported. We determined the outcome of 29 children with FLT3/ITD-positive acute myelogenous leukemia (AML) who underwent allogeneic HSCT in 4 pediatric centers. Eleven patients (38%) received matched related donor hematopoietic stem cells and 18 (62%) received alternative donors. Eighteen patients (62%) received total body irradiation (TBI)-based regimens. No patients experienced transplantation-related mortality. Eleven patients (38%) experienced relapsed disease. The cumulative incidence of relapse at 2 years was 34.7% (95% confidence interval [CI], 20.4% to 54.9%). Two-year disease-free survival (DFS) and overall survival (OS) were 65.3% (95% CI, 45.1% to 79.6%) and 82.2% (95% CI, 58.5% to 91.3%), respectively. There was no difference in the DFS of patients who received transplants from related donors versus the DFS of those who received transplants from alternative donors (hazard ratio [HR], 2.64; 95% CI, .79 to 8.76; P = .10), using univariate analysis. Patients with higher FLT3/ITD ratio at diagnosis had significantly worse DFS (HR, 1.42; 95% CI, 1.04 to 1.93; P = .03). The use of TBI in the preparative regimen was associated with superior DFS (HR, .29; 95% CI, .08 to .99; P = .04) and OS (HR, .07; 95% CI, .01 to .62; P = .002). We conclude that allogeneic HSCT improves DFS and OS in children with FLT3/ITD-positive AML compared with what has been reported in those treated with chemotherapy alone., (Copyright © 2015 American Society for Blood and Marrow Transplantation. Published by Elsevier Inc. All rights reserved.)

Background: Children under 5 represent 86% of annual malaria deaths in the world. Following increasing trends in international travel, cases of imported malaria are rising in North America. We describe the epidemiology of malaria diagnosed at a tertiary care pediatric center in the multicultural city of Toronto., Method: Retrospective chart review of all laboratory confirmed malaria from birth to <18 years between July 1, 1997 and June 30, 2013. Epidemiological data, travel history, chemoprophylaxis history, as well as clinical presentation, diagnosis and treatment were extracted., Results: In total 107 children were diagnosed with malaria in the 16 year time period. Plasmodium falciparum malaria was identified in 76 (71%), Plasmodium vivax in 28 (26%). Median age of infected children was 6.7 years where 35% of children were born in Canada, 63% were recent or previous immigrants. Of those who resided in Canada, reason for travel included visiting friends or relatives (VFR) 95% and tourism or education (5%). Most common countries of infection were Ghana (22%), Nigeria (20%) and India (14%). Median parasitemia at presentation to our institution was 0.4% (IQR 0.1-2.3) with a maximum parasitemia of 31%. Nineteen (18%) met the WHO criteria for severe malaria due to hyperparasitemia, with 3 of these cases also meeting clinical criteria for severe malaria. One third of patients had a delay in treatment of 2 or more days. Ten percent of children had seen two or more primary health care professionals prior to admission. Prophylaxis was documented in 22 (21%), and out of those, 6 (27%) were appropriate for the region of travel and only 1 case was documented as adherent to their prescription. There were no cases of fatality., Conclusion: Malaria continues to be a significant disease in returning travelers and immigrant or refugee populations. An increase in physician awareness is required. Appropriate pre-travel advice, insect protection measures, effective chemoprophylaxis is needed to reduce the incidence and improve the management of imported pediatric malaria.

We report the effects of two anti-cancer drugs, PBT-4, an experimental antagonist to the pro-inflammatory hepoxilins, and Gleevec (STI-571), an anti-leukaemic drug, on eicosanoid tumour levels in immunodeficient mice (NU/NU) xenografted with the leukaemic cell line, U937 bcl-xL. After the tumours had grown to 80-100mm(3) volume, an 8-day treatment with the drugs was initiated and the animals were monitored for 28 days. On various days, tumours were removed for measurement of 24 omega-6 eicosanoids. The data show remarkable direct correlation between inhibition of tumour AA release and 12-LOX products (including 12-HETE and hepoxilins) during PBT or STI treatment with tumour growth suppression. These findings suggest that inhibition of AA release may represent a novel underlying mechanism of action of PBT-4 (and STI) in vivo in suppressing tumour growth. As the PBT wears off, AA and 12-LOX products rise rapidly (Day 18) leading to the observed tumour growth spurt., (Copyright © 2013 Elsevier Inc. All rights reserved.)

Background: Peripheral T-cell lymphoma (PTCL) is rare in pediatric patients and is associated with worse outcome compared with other pediatric non-Hodgkin lymphomas. We report our institutional experience over a 10-year period., Methods: Patients were identified through the institutional oncology database. Data were abstracted through a detailed retrospective review of patient charts. Those with isolated cutaneous T-cell lymphoma were excluded from this analysis., Results: Thirteen patients were diagnosed with PTCL during the 10-year period. All presented with advanced disease. According to the WHO PTCL classification, 7 patients had PTCL not otherwise specified, 3 had hepatosplenic T-cell lymphoma and 3 had T-cell posttransplant lymphoproliferative disease. Six of the patients had previously received or were receiving immunosuppressive therapy at the time of their diagnosis. Patients were treated with various chemotherapeutic regimens, including B-cell non-Hodgkin lymphomas and T-cell acute lymphoblastic leukemia-like therapy. Patients who had refractory or recurrent disease were changed to alternative therapy. Eight patients underwent stem cell transplantation, 7 allogeneic and 1 autologous. Of the 13 patients, 7 died. Three patients died from disease progression, 3 died from treatment-related mortality, and 1 patient died from cardiac rejection. Six patients (46%) are alive and disease free at a median of 21 months (2 to 79 mo)., Conclusions: Children with PTCL have an unfavorable outcome. A standard approach to management of pediatric PTCL needs to be established to improve outcome. Because of the rarity of this condition, this will require collaborative studies.