Diagnostic Reliability of Paediatric Appendicitis Score & Ultrasound Scan in Children with Suspected Acute Appendicitis

Objective:  To evaluate the efficacy of Paediatric Appendicitis Score and ultrasound scan in the paediatric population. This study evaluates the best predictive measure for diagnosing acute appendicitis.Methodology: We conducted a prospective observational study on 120 children (02-13 years) in the department of Neonatal and Paediatric Surgery at The Children’s Hospital PIMS, Islamabad, with suspected appendicitis. Each patient was evaluated based on their Paediatric Appendicitis Score and ultrasound findings. We performed open appendectomy under general anaesthesia in patients with Paediatric Appendicitis Score ≥06 or who presented with severe tenderness on cough, TLC more than 10,000/mm3, or positive ultrasound findings.Results: In our study, the sensitivity and specificity of the Paediatric Appendicitis Score were 92.6% and 72.0%, respectively. Its sensitivity and specificity were 84.09% and 85.71%, respectively, with cutoff ≥6 combined with ultrasound findings. The combined sensitivity and specificity of Paediatric Appendicitis Score <6 and ultrasound were 85.71% and 94.44%, respectively.Conclusion: Paediatric Appendicitis Score is a useful diagnostic tool for suspected appendicitis in pediatric population. Its efficacy is significantly increased when combined with ultrasound. Combined application of the Paediatric Appendicitis Score with ultrasonography helps to rule out negative appendectomies and reduces complications associated with delayed diagnosis

Association Of BCR-ABL Alternative Splice Variants with Disease Progression, Treatment Response and Survival in Chronic Myeloid Leukemia Patients Treated with Firstline imatinib Monotherapy

Background: Alternative RNA splicing has diverse biological effects in heath as well as disease. It also contributes to cancer onset and progression. Chronic Myeloid Leukemia (CML) results due to BCR-ABL fusion oncogene that is created due to chromosomal translocation t [9; 22] [q34; q11]). BCR-ABL is target of tyrosine kinase inhibitors (TKIs). BCR-ABL through alternative splicing can generate b2a2, b3a2 and some other rare splicing variants. BCR-ABL variants may vary in their response to TKI treatment and disease progression potential, which is a major factor contributing to dismal treatment outcome in CML. Objective: The objective of this study is to investigate correlation of BCR-ABL splice variants with TKI treatment outcome and survival in three phases of CML that has rarely been studied previously.Methods: BCR-ABL splice variants were studied using reverse transcriptase PCR (RT-PCR). in 70 CML patients from three phases of CML who were receiving imatinib (TKI) treatment.Results: Frequencies of different BCR/ABL splice variants like b3a2, b2a2 and b3a2+b2a2 were 49 (70%), 15 (21.4%) and 6 (8.6%), respectively. Splice variant b2a2 were more common (53.3%) in chronic phase CML (CP-CML) while b3a2 had higher frequency in advanced phases of CML (44.9%). CML patients with b2a2 transcript had better complete cytogenetic response and major molecular response to TKI treatment overall (100% vs. 24.5%) as well as in CP-CML (100% vs. 85.7%) and superior survival when compared to patients with b3a2 splice variant. All patients who died had male gender, less than 33 years age, b3a2 transcript, advanced phases of CML and imatinib resistance.Conclusions: Splice variant b3a2 was associated with CML progression, poorer survival and inferior treatment outcome as compared to b2a2. Further investigations on BCR-ABL splice variants and their roles in CML pathogenesis can provide deeper insights into CML biology and new targets for BCR-ABL positive leukemia treatment.          Keywords: CML; BCR-ABL splice variants; Progression; Survival; Treatment outcome