Panel‑based next‑generation sequencing facilitates the characterization of childhood acute myeloid leukemia in clinical settings

Acute myeloid leukemia (AML) accounts for ~20% of pediatric leukemia cases. The prognosis of pediatric AML has been improved in recent decades, but it trails that of most other types of pediatric cancer, with mortality rates of 30‑40%. Consequently, newer more targeted drugs are required for incorporation into treatment plans. These newer drugs selectively target AML cells with specific gene alterations. However, there are significant differences in genetic alterations between adult and pediatric patients with AML. In the present study, inexpensive and rapid next‑generation sequencing (NGS) of >150 cancer‑related genes was performed for matched diagnostic, remission and relapse (if any) samples from 27 pediatric patients with AML. In this analysis, seven genes were recurrently mutated. KRAS was mutated in seven patients, NRAS was mutated in three patients, and KIT, GATA1, WT1, PTPN11, JAK3 and FLT3 were each mutated in two patients. Among patients with relapsed AML, six harbored KRAS mutations at diagnosis; however, four of these patients lost these mutations at relapse. Additionally, two genetic alterations (FLT3‑ITD and TP53 alterations) were detected among patients who eventually relapsed, and these mutations are reported to be adverse prognostic factors for adult patients with AML. This panel‑based, targeted sequencing approach may be useful in determining the genetic background of pediatric AML and improving the prediction of treatment response and detection of potentially targetable gene alterations. RAS pathway mutations were highly unstable at relapse; therefore, these mutations should be chosen as a target with caution. Incorporating this panel‑based NGS approach into the clinical setting may allow for a patient‑oriented strategy of precision treatment for childhood AML

Effects of Paroxetine and Milnacipran on Pain Disorder

The outcomes of treatment for pain disorder are generally disappointing: symptoms are poorly controlled, they are seldom managed by experts, and they are often long standing. The aim of the present study was to compare the therapeutic effectiveness of paroxetine and milnacipran for outpatients with pain disorder. The study was performed on 43 consecutive outpatients with pain disorder diagnosed according to DSM-IV-TR criteria. Patients were treated with either antidepressant for 8 weeks. Pain was self-assessed using the Short-Form McGill Pain Questionnaire (SF-MPQ), the total Pain Rating Index (t-PRI), Present Pain Intensity (PPI), and visual analogue scale (VAS). In addition, pain was evaluated objectively using Pain Vision (a machine devised by NIPRO for semiquantitative measurements). Possible depressive symptoms were rated on the Hamilton Depression Scale (HAM-D) and the Zung Self-rating Depression Scale (SDS). Although VAS scores decreased significantly over the course of the 8-week trial in both the paroxetine- and milnacipran-treated groups (from 6.6 ± 2.3 to 4.8 ± 3.0 [P = 0.01] and from 7.5 ± 2.4 to 5.4 ± 3.3 [P = 0.03], respectively), the t-PRI decreased only in the paroxetine group (from 13.9 ± 10.1 to 7.6 ± 7.5; P = 0.01). The Pain Vision indicated a tendency for decreased pain in both groups, with no significant differences between them. There were no significant changes in the SDS in either group, but the HAM-D decreased significantly in the milnacipran-treated group (from 7.8 ± 4.0 to 6.7 ± 3.9; P = 0.04). The results of the present study suggest that both paroxetine (a selective serotonin re-uptake inhibitor) and milnacipran (a selective serotonin-noradrenaline re-uptake inhibitor) may decrease pain in individuals with pain disorder

Minilaparotomy Approach for Giant Mutinous Cystadenoma of the Ovary in Children: Report of Two Cases

Mucinous cystadenomas (MCAs) are rare benign neoplasms in children. To the best of our knowledge, only 22 cases in children have been described. MCAs may reach huge sizes, and thus are not readily amenable to laparoscopic treatment due to the risk of rupture and the limited working space. We report two cases of giant MCA of the ovary treated by minilaparotomy. In case 1, a 12-year-old girl was admitted with abdominal pain and vomiting. Diagnostic imaging showed a large polycystic mass occupying nearly the whole abdominal cavity. With a provisional diagnosis of ovarian cyst, surgery was performed. The cyst was punctured under direct vision though a small subumbilical incision. After aspiration of 2,000ml of mucinous fluid, laparoscopic examination revealed a tumor originating from the left ovary. Left oophorectomy was performed through an 8-cm incision in the left lower abdomen. The histopathological diagnosis was MCA. In case 2, a 15-year-old girl presented with slowly increasing abdominal distension over 5 months. A polycystic mass measuring 36 × 21 × 14cm was evident on imaging. After drainage of 9,500ml of clear mucinous fluid, right oophorectomy was performed through a small (5cm) midline incision. The final pathology revealed a benign MCA. No recurrence has been detected for 2 years postoperatively in case 1 and for 6 years postoperatively in case 2

Neutrophil elastase in amniotic fluid as a predictor of preterm birth after emergent cervical cerclage

Introduction. The aim of this study was to investigate neutrophil elastase (NE) in amniotic fluid as a potential marker for predicting pregnancy continuation. Material and methods. We enrolled 34 pregnant women with bulging fetal membrane during the second trimester who underwent emergent cerclage after confirming the absence of intrauterine infection (amniotic fluid glucose >= 15 mg/dL). Amniotic fluid NE levels were compared between women who completed and did not complete 30, 34, and 36 weeks of gestation, and the optimal cut-off value for predicting pregnancy continuation was estimated. Moreover, the differences in the duration of continued pregnancy were compared between women with NE levels above and below the optimal cut-off value. Results. The optimal cut-off value for NE in amniotic fluid that predicted pregnancy continuation beyond 30, 34, and 36 weeks of gestation was 180 ng/mL; this cut-off value had a sensitivity, specificity, positive predictive value, and negative predictive value of 84.0, 77.8, 91.3, and 63.7% beyond 30 weeks of gestation; 87.5, 80.0, 91.5, and 72.3% beyond 34 weeks of gestation; and 85.0, 71.4, 80.9, and 76.9% beyond 36 weeks of gestation, respectively. The duration of continued pregnancy from emergent cerclage to delivery was significantly longer in women with amniotic fluid NE = 180 ng/mL (44.8 +/- 14.3 days). Conclusion. The NE levels in amniotic fluid may serve as a useful marker for predicting the duration of continued pregnancy after cervical cerclage

Diagnosis of osteoporosis from dental panoramic radiographs using the support vector machine method in a computer-aided system

<p>Abstract</p> <p>Background</p> <p>Early diagnosis of osteoporosis can potentially decrease the risk of fractures and improve the quality of life. Detection of thin inferior cortices of the mandible on dental panoramic radiographs could be useful for identifying postmenopausal women with low bone mineral density (BMD) or osteoporosis. The aim of our study was to assess the diagnostic efficacy of using kernel-based support vector machine (SVM) learning regarding the cortical width of the mandible on dental panoramic radiographs to identify postmenopausal women with low BMD.</p> <p>Methods</p> <p>We employed our newly adopted SVM method for continuous measurement of the cortical width of the mandible on dental panoramic radiographs to identify women with low BMD or osteoporosis. The original X-ray image was enhanced, cortical boundaries were determined, distances among the upper and lower boundaries were evaluated and discrimination was performed by a radial basis function. We evaluated the diagnostic efficacy of this newly developed method for identifying women with low BMD (BMD T-score of -1.0 or less) at the lumbar spine and femoral neck in 100 postmenopausal women (≥50 years old) with no previous diagnosis of osteoporosis. Sixty women were used for system training, and 40 were used in testing.</p> <p>Results</p> <p>The sensitivity and specificity using RBF kernel-SVM method for identifying women with low BMD were 90.9% [95% confidence interval (CI), 85.3-96.5] and 83.8% (95% CI, 76.6-91.0), respectively at the lumbar spine and 90.0% (95% CI, 84.1-95.9) and 69.1% (95% CI, 60.1-78.6), respectively at the femoral neck. The sensitivity and specificity for identifying women with low BMD at either the lumbar spine or femoral neck were 90.6% (95% CI, 92.0-100) and 80.9% (95% CI, 71.0-86.9), respectively.</p> <p>Conclusion</p> <p>Our results suggest that the newly developed system with the SVM method would be useful for identifying postmenopausal women with low skeletal BMD.</p