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Agata Rocka,1 Maria Suchcicka,2 Aleksandra M Jankowska,2 Magdalena M Woźniak,1 Monika Lejman3 1Pediatric Radiology, Medical University of Lublin, Medical University of Lublin, Prof. Antoni Gębali 6, Lublin, 20-093, Poland; 2Student Scientific Society of Independent Laboratory of Genetic Diagnostics, Medical University of Lublin, Prof. Antoni Gębali 6, Lublin, 20-093, Poland; 3Independent Laboratory of Genetic Diagnostics, Medical University of Lublin, Prof. Antoni Gębali 6, Lublin, 20-093, PolandCorrespondence: Agata Rocka, Pediatric Radiology, Medical University of Lublin, Medical University of Lublin, Prof. Antoni Gębali 6, Lublin, 20-093, Poland, Email agatarocka2@gmail.comAbstract: The aim of this study is to analyze available research on targeting signaling pathways for the development of new drugs in patients with T-cell acute lymphoblastic leukemia (T-ALL). This analysis focuses specifically on the role of LCK tyrosine kinase and mTOR signaling pathways in pediatric patients. Outcome: Current literature suggests that these pathways play a significant role in the regulation of T-cell cycles, making them potential therapeutic targets. However, despite promising findings, there remains a need for further research, particularly in pediatric populations, to fully understand the therapeutic implications and to optimize drug development. The conclusion drawn from this analysis highlights the significant influence of LCK and mTOR on T-cell cycle regulation, underscoring the importance of continued investigation in this area.Keywords: T-ALL, pediatric, signaling pathways, targeted therapy

To assess both sensitivity and specificity of digital chest radiography alone and in conjunction with dual-exposure dual-energy chest radiography for the detection and classification of pulmonary nodules. One hundred patients with a total of 149 lung nodules (3-45 mm; median, 11 mm) confirmed by CT were included in this study. Dual-exposure dual-energy chest radiographies of each patient were obtained using a CsI detector system. Experienced board-certified chest radiologists from four different medical centers in Europe reviewed standard chest radiographs alone and in conjunction with dual-energy images blinded and in random order. The reviewers rated the probability of presence, calcification and malignancy of all lung nodules on a five-point rating scale. Lesions detected were identified by applying a specific coordinate system to enable precise verification by the study leader. A receiver-operating characteristic (ROC) analysis was performed. In addition to the 149 true-positive CT proven lesions, 236 false-positive lung nodules were described in digital chest radiographies in conjunction with dual-energy chest radiographies. The cumulative sensitivity of chest radiography in conjunction with dual energy was 43%, specificity was 55%. For digital radiography alone, sensitivity was 35% and specifity was 83%. For the dual energy system, positive predictive value was 58%, and negative predictive value was 66% compared to the digital radiography with a positive predictive value of 59% and a negative predictive value of 65%. Areas under the curve in a ROC analysis resulted in 0.631 (95% confidence interval =0.61 to 0.65) for radiography with dual energy and 0.602 (95% confidence interval =0.58 to 0.63) for digital radiography alone. This difference was not statistically significant. For the detection of lesion calcification or the determination of malignancy, ROC analysis also failed to show significant differences. CsI-based flat-panel dual-exposure dual-energy imaging added to standard chest radiography did not show statistically significant improvement for the detection of pulmonary nodules, nor the identification of calcifications, nor the determination of malignancy. [ABSTRACT FROM AUTHOR]

Intrathecal (IT) dosing (ie, injection into the subarachnoidal space at the lumbar region) is a common route of administration in cynomolgus monkey preclinical safety studies conducted for antisense oligonucleotides (ASO) that target central nervous system diseases. Herein we report on neurological signs that have been observed in 28 IT studies conducted in 1,016 cynomolgus monkeys. Neurological signs were classified into 5 groups: (1) A nonadverse transient absence of lower spinal reflexes. This observation occurred at low incidence in nontreated animals and in those that were injected artificial cerebrospinal fluid. The incidence increased in animals that were injected an ASO. Reflexes were present again at 24 hours or 48 hours after dosing. The incidence appeared to increase with dose. (2) Test-article-related adverse muscle tremor or muscle spasticity occurring during the injection procedure or immediately thereafter. In one-third of animals this finding responded to treatment with diazepam, in two-third it required euthanasia. (3) Neurological findings occurring between 30 minutes and 4 hours after dosing were characterized by any combination of ataxia, paresis, nystagmus, urinary incontinence, or muscle tremor. Those conditions either spontaneously resolved or they slowly worsened, eventually resulting in a poor general condition. (4) Neurological findings due to spinal cord injury were characterized by rapidly progressing paralysis of hind limbs. Magnetic resonance imaging revealed a focal hyperintense lesion, indicative of spinal cord necrosis. (5) Test-article-related adverse hind limb paresis or paralysis that occurred between 2 and 18 days after dosing. Those findings were rare and resulted in a poor general condition requiring euthanasia.

Many potential drugs for treatment of neurodegenerative diseases, particularly antisense oligonucleotides (ASOs), are administered via lumbar intrathecal injection, because these drugs do not cross the blood-brain barrier. Intrathecal injection is a well-established method in cynomolgus monkeys, a species that is used in preclinical safety assessment when other nonrodent species cannot be used. The authors completed intrathecal ASO administration in over 30 preclinical safety studies (>1000 animals and >4500 dose administrations) during which we observed 3 cases of procedure-related spinal cord necrosis (incidence <0.1%). We describe clinical symptoms, diagnostic approaches, morphological features, and prognosis of this rare injury, and compare these findings with typical drug-related findings of ASOs dosed by intrathecal injection. The low incidence of procedure-related and dose-limiting lesions confines this analysis to a small sample set. The pattern of effects is similar across all monkeys despite differences in age, body weight, and intrathecal injection site. All 3 cases presented a combination of the following findings: blood in cerebrospinal fluid at time of injection, clinical signs that increase in severity within a day of dosing, lameness of both hind limbs, reduced muscle tone, and loss of patellar, foot grip, and/or anal reflexes. In all cases, magnetic resonance imaging (MRI) showed a linear hyperintense lesion in the lumbar spinal cord. In 2 cases, this hyperintensity was associated with evidence of spinal cord edema. We conclude that a pattern of in-life and pathology findings, including noninvasive MRI assessment, is indicative of procedure-related effects.

Objective: To compare the sensitivity and specificity of two- (2D) and three- (3D) dimensional transperineal ultrasound (TPUS) and 3D endovaginal ultrasound (EVUS) with the gold standard 3D endoanal ultrasound (EAUS) in detecting residual defects after primary repair of obstetric anal sphincter injuries (OASIS)., Methods: External (EAS) and internal (IAS) anal sphincters were evaluated by the four ultrasound modalities in women with repaired OASIS. 2D-TPUS was evaluated in real-time, whereas 3D-TPUS, 3D-EVUS and 3D-EAUS volumes were evaluated offline by six blinded readers. The presence/absence of any tear in EAS or IAS was recorded and defects were scored according to the Starck system. Sensitivity, specificity and predictive values were calculated, using 3D-EAUS as reference standard. Inter- and intraobserver analyses were performed for all 3D imaging modalities. Association between patients' symptoms (Wexner score) and ultrasound findings (Starck score) was calculated., Results: Images from 55 patients were analyzed. Compared with findings on 3D-EAUS, the agreement for EAS evaluation was poor for 3D-EVUS (κ = 0.01), fair for 2D-TPUS (κ = 0.30) and good for 3D-TPUS (κ = 0.73). The agreement for IAS evaluation was moderate for both 3D-EVUS (κ = 0.41) and 2D-TPUS (κ = 0.52) and good for 3D-TPUS (κ = 0.66). Good intraobserver (3D-EAUS, κ = 0.73; 3D-TPUS, κ = 0.78) and interobserver (3D-EAUS, κ = 0.68; 3D-TPUS, κ = 0.60) agreement was reported. Significant association between Starck and Wexner scores was found only for 3D-EAUS (Spearman's rho = 0.277, P = 0.04)., Conclusions: 2D-TPUS and 3D-EVUS are not accurate modalities for the assessment of anal sphincters after repair of OASIS. 3D-TPUS shows good agreement with the gold standard 3D-EAUS and a high sensitivity in detecting residual defects. It, thus, has potential as a screening tool after primary repair of OASIS. Copyright © 2016 ISUOG. Published by John Wiley & Sons Ltd., (Copyright © 2016 ISUOG. Published by John Wiley & Sons Ltd.)

The aim of the ultrasound (US) screening program was to detect neoplastic lesions in children, together with other pathologies of the developmental age in the area of the neck, abdomen, female pelvis, and scrotum in boys.US screening scans, including cervical, abdominal, pelvical, and scrotal US, were performed in the population of asymptomatic children aged from 9 months to 6 years. The children were scanned in Mobile Pediatric US Unit, consisting of 2 independent consulting rooms.The scans of 14,324 children were analyzed, 7247 boys and 7077 girls. Totally 42,538 US examinations were performed, including 14,187 cervical scans, 14,259 abdominal scans, 6942 female pelvical scans, and 7150 scrotal scans. Totally 5426 abnormalities were detected, which represent 12.7% of all examinations and 30% of patients. Three tumors were recognized, which are renal malignant tumor diagnosed as Wilms tumor, neurogenic tumor of the rib, and teratoma of the testis.US screening in pediatric population can be used to reveal lesions inaccessible to clinical examination, like tumors or other pathologies of developmental age before the onset of clinical symptoms. Due to the large number of detected abnormalities it should be recommended to the whole population of certain age., Competing Interests: The authors have no conflicts of interest to disclose.

Background: Testicular adrenal rest tumors (TART) are the nodular testicular lesions deriving from the adrenal remnant tissue reported in boys and men with congenital adrenal hyperplasia. Until now, the diagnostics of TART have been based on a combination of clinical features, imaging methods (primarily two dimensional ultrasound--2D US), response of the foci to glycocorticosteroid (GCS) therapy and exclusion of the neoplastic process. Application of 2D US supplies however a limited range of information about the volume, demarcation, structure and vascularization of the lesions., Objective: To define whether the use of 3D US, power Doppler and elastography changes the algorithm of the diagnostics and monitoring or treatment of TART., Material and Methods: In this study, modern ultrasound techniques such as 3D US and elastography were introduced in two boys with TART., Results: The 3D power Doppler option gives the opportunity for accurate assessment of the volume of testes and adrenal tissue foci and their vascularization. Sonographic elastography allows the assessment of stiffness of adrenal tissue areas compared to normal testis parenchyma., Conclusion: The use of these modern techniques enables more adequate and advanced diagnostics, and more precise monitoring of the effects of treatment in patients with TART., (Copyright © 2013 Journal of Pediatric Urology Company. Published by Elsevier Ltd. All rights reserved.)

Purpose: The aim of the study was quantitative and qualitative assessments of scrotal abnormalities diagnosed in boys 8 to 36 months old during ultrasound screening and estimation if these abnormalities influence testes volume., Materials and Methods: High frequency scrotal ultrasound was performed in 1448 patients aged 8-36 months as additional exam during screening ultrasound program for children including cervical and abdominal ultrasound. The mean age of examined boys was 17 months. For further analysis the children were divided in 5 age groups., Results: The abnormalities in scrotal ultrasound were found in 20.1% of boys. Undescended, cryptorchid testes were found in 4.8% of patients, mobile testicle in 7.6% and hydrocele in 2.8%. The volume of undescended testes was statistically lower than volume of the descended testes in 3 youngest groups of boys (p=0.003-0.011). The volume of mobile testicles did not increase with age, while in patients with hydrocele the testicular volume decreased with age., Conclusion: Scrotal screening ultrasound performed in boys up to 3 years old may deliver information about the number and type of existing pathologies as well as their influence on the testicular volume. The volume of the pathological testes was lower than the volume of the normal ones. Improper growth of testes may potentially have important clinical implication for the function of testes in the future., (Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.)

Objectives: Assessment of the urethral complex and defining its morphological characteristics with 3-dimensional endovaginal ultrasonography with the use of high frequency rotational 360° transducer. Defining inter-observer reliability of the performed measurements., Materials and Methods: Twenty-four asymptomatic, nulliparous females (aged 18-55, mean 32 years) underwent high-frequency (12MHz) endovaginal ultrasound with rotational 360° and automated 3D data acquisition (type 2050, B-K Medical, Herlev, Denmark). Measurements of the urethral thickness, width and length, bladder neck-symphysis distance, intramural part of the urethra as well as rhabdosphincter thickness, width and length were taken by three investigators. Descriptive statistics for continuous data was performed. The results were given as mean values with standard deviation. The relationships among different variables were assessed with ANOVA for repeated measures factors, as well as T-test for dependent samples. Intraclass correlation (ICC) was calculated for each parameter. Intra- and interobserver reliability was assessed. Statistical significance was assigned to a P value of <0.05 (two-tailed)., Results: Excellent reliability was observed for urethral measurements (length, width, thickness and volume) (ICC>0.8) and good reliability for rhabdosphincter measurements (ICC>0.6) between all three investigators., Conclusions: Advanced EVUS provides detailed information on anatomy and morphology of the female urethral complex. Our results show that 360° rotational transducer with automated 3D acquisition, currently routinely used for proctological scanning is suitable for the reliable assessment of the urethral complex and can be applied in a routine diagnostics of pelvic floor disturbances in females., (Copyright © 2010 Elsevier Ireland Ltd. All rights reserved.)