Prognostic Significance of Survivin in Pediatric Acute Lymphoblastic Leukemia

Impaired apoptosis is mediated by members of the inhibitor of apoptosis proteins (IAP) family such as survivin. Survivin was described in number of different tumors and found to correlate with poor prognosis in a variety of cancers including hematologic malignancies. The aim of this study was to determine survivin in pediatric ALL and compare it with clinical and hematological findings, response to therapy and outcome. Flowcytometry was used for detection of intracellular survivin and determine its mean fluorescence intensity (MFI) in bone marrow mononuclear cells. Patients were followed up for 28 months after induction therapy. Survivin was detected in 63.3% of the patients BM. In spite of no association of survivin levels with established risk factors (P > 0.05) except with high WBC, there was significant higher level of survivin expression in high risk group patients when patients were stratified into high and standard risk groups. According to response to induction therapy, there was no significant difference, in survivin level between patients who achieved CR, RD and ED. However, patients suffering relapse of the disease, had a significant higher basal level of survivin than patients still in remission. Over expression of survivin is a candidate parameter to determine poor prognosis in ALL patients and it may serve to refine treatment stratification with intensification of therapy in those patients prone to relapse.     

Parasitic contamination in wastewater and sludge samples in Tunisia using three different detection techniques

The limited availability of water results in the reuse of wastewater or sludge. The Tunisian wastewater regulatory guidelines have specific limits for ova of helminths (<1 egg/l) but none for protozoan parasites. We assessed the presence and loads of parasites in 20 samples of raw, treated wastewater and sludge collected from six wastewater treatment plants. Samples were tested by microscopy using the modified Bailenger method (MBM), immunomagnetic separation (IMS) followed by immunofluorescent assay microscopy, and PCR and sequence analysis for the protozoa Cryptosporidium and Giardia. The seven samples of raw wastewater had a high diversity of helminth and protozoa contamination. Giardia spp., Entamoeba histolytica/dispar, Entamoeba coli, Ascaris spp., Enterobius vermicularis, and Taenia saginata were detected by MBM, and protozoan loads were greater than helminth loads. Cryptosporidium and Giardia were also detected by IMS microscopy and PCR. Six of the eight samples of treated wastewater had parasites: helminths (n = 1), Cryptosporidium (n = 1), Giardia (n = 4), and Entamoeba (n = 4). Four of five samples of sludge had microscopically detectable parasites, and all had both Cryptosporidium and Giardia. The genotypes and subtypes of Cryptosporidium and Giardia were of both human and animal origin. These findings suggest that it may be important to monitor the presence of protozoan parasites in treated wastewater and sludge in Tunisia.     

Coagulation disorders and inhibitors of coagulation in children from Mansoura, Egypt

Disorders of coagulation in children often prove challenging to the medical care team. The aims of this study were to assess the spectrum and prevalence of coagulation disorders among children attending Mansoura University Children Hospital (MUCH), Mansoura, Egypt. A total of 105 pediatric patients were referred to MUCH. They were divided into two groups: congenital coagulation disorders (75 cases, age 45.36 +/- 48.59 months), and acquired coagulation disorders (30 cases, age 56.13 +/- 61.61 months). All patients were subjected to thorough history taking including the nature of bleeding, family, past history, mode of inheritance, and detailed physical findings. Hemostatic tests included: platelet count, bleeding time (BT), prothrombin time (PT), activated partial thromboplastin time (APTT), thrombin time (TT). Specific tests in the congenital group include assay of coagulation factors according to each disorder, Von Willebrand factor assay, ristocetin aggregation test, APTT mixing study for detection of inhibitors in complicated hemophilia cases, F VIII C to VWAg ratio with cut off 0.7 for detection of carriers in some hemophilia A families. Congenital disorders constituted 71.4% of the studied cases vs. 28.6% for acquired disorders. Hemophilia A (42.85%), hemophilia B (14.28%) and liver diseases (14.28%) represented the majority of the studied cases. Mild and moderate cases of hemophilia A and B are more frequent than severe cases in both types. Male sex is more frequent than female in the congenital group (94.7 vs. 5.3%, P < 0.001). Direct correlation existed between factor level assay and severity of hemophilia (r = 0.73, P = 0.006). Three mothers and one sister were identified as carrier out of four families. Anti-clotting factors inhibitor was detected in 18.2% of patients with hemophilia A and in 9.1% with hemophilia B. In conclusion, our study found that hemophilias are the most prevalent congenital coagulation disorders among children. Attention must be given for detection of hemophilia carriers and inhibitors of clotting factors.     

Utilization of amplicon-based targeted sequencing panel for the massively parallel sequencing of sporadic hearing impairment patients from Saudi Arabia

Background

Hearing Impairment (HI) can have genetic or environmental causes and in some cases, an interplay of both. Genetic causes are difficult to determine as mutations in more than 90 genes have been shown recently to be responsible for HI. Providing a genetic diagnostic test for HI is therefore a challenge especially for ethnic groups where GJB2 mutations are shown to be rare.

Results

Here we show the design and implementation of an amplicon-based targeted sequencing panel that allows the simultaneous sequencing of 87 HI genes. Mutations identified included known pathogenic mutations and novel variants with unknown significance. The diagnostic rate of this panel is 28 % when only pathogenic variants were reported. However, an additional 28 % harbored recurrent combinations of novel or rare single nucleotide variants in the OTOF or PCDH15 genes. Such combinations were not identified in healthy individuals.

Conclusions

Targeted sequencing approach is a very useful strategy for the identification of mutations affecting the HI genes because of its relatively fast turn-around time and cost effectiveness compared to whole-exome sequencing. Further novel or rare variants could be identified by implementing a large-scale screening of HI using our panel which will eventual lead to a higher diagnostic rate.

     

Validation of New Care Coordination Quality Measures for Children with Medical Complexity

Objectives

To validate new caregiver-reported quality measures assessing care coordination services for children with medical complexity (CMC).

AI-Based Automated Lipomatous Tumor Segmentation in MR Images: Ensemble Solution to Heterogeneous Data

Deep learning (DL) has been proposed to automate image segmentation and provide accuracy, consistency, and efficiency. Accurate segmentation of lipomatous tumors (LTs) is critical for correct tumor radiomics analysis and localization. The major challenge of this task is data heterogeneity, including tumor morphological characteristics and multicenter scanning protocols. To mitigate the issue, we aimed to develop a DL-based Super Learner (SL) ensemble framework with different data correction and normalization methods. Pathologically proven LTs on pre-operative T1-weighted/proton-density MR images of 185 patients were manually segmented. The LTs were categorized by tumor locations as distal upper limb (DUL), distal lower limb (DLL), proximal upper limb (PUL), proximal lower limb (PLL), or Trunk (T) and grouped by 80%/9%/11% for training, validation and testing. Six configurations of correction/normalization were applied to data for fivefold-cross-validation trainings, resulting in 30 base learners (BLs). A SL was obtained from the BLs by optimizing SL weights. The performance was evaluated by dice-similarity-coefficient (DSC), sensitivity, specificity, and Hausdorff distance (HD95). For predictions of the BLs, the average DSC, sensitivity, and specificity from the testing data were 0.72 \(\pm\) 0.16, 0.73 \(\pm\) 0.168, and 0.99 \(\pm\) 0.012, respectively, while for SL predictions were 0.80 \(\pm\) 0.184, 0.78 \(\pm\) 0.193, and 1.00 \(\pm\) 0.010. The average HD95 of the BLs were 11.5 (DUL), 23.2 (DLL), 25.9 (PUL), 32.1 (PLL), and 47.9 (T) mm, whereas of SL were 1.7, 8.4, 15.9, 2.2, and 36.6 mm, respectively. The proposed method could improve the segmentation accuracy and mitigate the performance instability and data heterogeneity aiding the differential diagnosis of LTs in real clinical situations.