Breast cancer is one of the major causes of female morbidity and mortality, accounting for ~25% of the total cancer cases in women. Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic α subunit ( PIK3CA ) mutations serve a major role in downstream signaling of receptor tyrosine kinases. The present study aimed to elucidate the frequency of exon 9 and 20 mutations of PIK3CA and their role in disease progression. A total of 118 tumor samples from confirmed breast cancer patients were collected from the histopathology laboratory at King Fahd Hospital of the University (Al-Khobar, Saudi Arabia). Sanger sequencing was performed on extracted DNA to identify the mutations on exons 9 and 20 of PIK3CA . The results were further validated by competitive allele-specific TaqMan polymerase chain reaction. Three mutations, namely E542K and E545K within exon 9, and H1047R within exon 20, were observed in 25 patients (21.2%). Among these, 18 patients carried the H1047R mutation of the kinase domain, while the remaining 7 patients carried mutations in the helical domain. PIK3CA mutations were associated with the estrogen receptor-positive/progesterone receptor-positive (ER + /PR + ) group of tumors in contrast to the ER − /PR − group (P=0.021). Furthermore, it was observed that the PIK3CA mutation was associated with a poor disease prognosis. Taken together, the current study emphasized the potential of PIK3CA mutations as an important biomarker for breast cancer classification and the possible use of PIK3CA inhibitor as targeted therapy for breast cancer.

Purpose: Autosomal dominant polycystic kidney disease (ADPKD) is characterized by progressive development of kidney cysts and enlargement and dysfunction of the kidneys. The Consortium of Radiologic Imaging Studies of the Polycystic Kidney Disease (CRISP) cohort revealed that 89.1% had either a PKD1 or PKD2 mutation. Of the CRISP patients with a genetic cause detected, mutations in PKD1 accounted for 85%, while mutations in the PKD2 accounted for the remaining 15%. Here, we report exome sequencing of 16 Saudi patients diagnosed with ADPKD and 16 ethnically matched controls. Methods: Exome sequencing was performed using combinatorial probe-anchor synthesis and improved DNA Nanoballs technology on BGISEQ-500 sequencers (BGI, China) using the BGI Exome V4 (59 Mb) Kit. Identified variants were validated with Sanger sequencing. Results: With the exception of GC-rich exon 1, we obtained excellent coverage of PKD1 (mean read depth ¼ 88) including both duplicated and non-duplicated regions. Of nine patients with typical ADPKD presentations (bilateral symmetrical kidney involvement, positive family history, concordant imaging, and kidney function), four had protein truncating PKD1 mutations, one had a PKD1 missense mutation, and one had a PKD2 mutation. These variants have not been previously observed in the Saudi population. In seven clinically diagnosed ADPKD cases but with atypical features, no PKD1 or PKD2 mutations were identified, but rare predicted pathogenic heterozygous variants were found in cystogenic candidate genes including PKHD1, PKD1L3, EGF, CFTR, and TSC2. Conclusions: Mutations in PKD1 and PKD2 are the most common cause of ADPKD in Saudi patients with typical ADPKD.

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Background: Febrile neutropenia (FN) is one of most common and potentially lethal complications in patients with cancer during chemotherapy. The Oncology Department of the Children's Hospital Lahore Pakistan is a 60 bedded unit providing free treatment to over 1300 new childhood cancer cases each year and over 200 admissions per month with bed occupancy rate around 200%. The department receives childhood cancer cases not only from Pakistan but also from Afghanistan. Therefore it's very challenging to treat cancer and infection parallel with increased burden on the public sector hospital providing free treatment as well as on health professionals managing these patients with advanced stages and frequent infection episodes. Aim: The objective of this study is to evaluate the burden of FN in resource limited settings like a public sector hospital in Pakistan. A prospective review of data of patients treated for febrile neutropenia from October to December 2017 in the Haematology/Oncology Department of The Children's Hospital Lahore after IRB approval. The data were analyzed by using SPSS 20. Results: 250 patients were treated for FN during these three months 59% of them male and mean age 6.27 years. Among diagnoses, 58% had acute lymphoblastic leukaemia, 16% sarcomas, 10% lymphoma and 16% other solid malignancies on different chemotherapy regimens. 53% received their chemo during last 3 days and 35% in the last week prior to FN admission. 84% of them were receiving either induction or intensive phase protocols. 48% had respiratory tract infection followed by AGE 25%, fever alone in 20%, 82% cases had mucositis. 52% cases had symptoms of more than 24 hours before seek treatment of FN. ANC (absolute neutrophil count) was < 100 in 60% and platelets < 50,000 in 56% cases on arrival. 57% cases stayed 1-3 hours drive from the Children´s hospital and only 44% parents had adequate awareness of FN management. Regarding the outcome 81% discharged home, 16% expired (mainly FN and progressive disease) and 3% abandoned treatment. G-CSF (granulocyte-colony stimulating factor) was used in 30% (0.026 for RX cost and 0.043 hospital stay) and blood products in 75%, inotropes used in 16% with mean estimated cost of 15,000 RS/patient (total 3.8 million RS) with 95% staying > 48 hrs. 61 cultures were positive mainly urine, blood, ENT, wound, CSF. 92% were Gram negative with majority Klebsiella followed by Pseudomonas, E. coli and Citrobacter species. There were no central lines used. Conclusion: This study described that FN has been a profound burden in childhood cancer care in public sector hospital in resource limited settings like Pakistan. There is immense need to health educate the parents, nurses and doctors for standard care of febrile neutropenia along with sustainable social support and shared care oncology as being provided in developed countries to share the load of primary treatment centers aiming for decreased morbidity and mortality.

BackgroundCardiovascular disease is a leading cause of morbidity and mortality. Therefore, it is essential to prevent cardiovascular diseases by correcting modifiable risk factors such as lowering lipid levels, lowering blood pressure, improving eating habits, giving up smoking, etc. The present study assessed the efficacy of herbal preparation containing Allium sativum (A. sativum), Commiphora mukul (C. mukul), and Trigonella foenum-graecum (T. foenum-graecum) in patients with hyperlipidemia. MethodologyPatients were given extracts of A. sativum 350 mg, T. foenum-graecum 350 mg, C. mukul 200 mg, Picrorhiza kurroa (P. kurroa) 200 mg, and Piper nigrum (P. nigrum) 5 mg. Unichem Laboratories, Mumbai, provided placebo tablets similar in shape and size to herbal tablets. Patients were assessed for compliance, and a complete lipid profile was done at DO, D15, D46, D76, and D106. In addition, total cholesterol and highdensity lipoprotein-cholesterol (HDL-C) serum triglyceride were estimated by the respective methods throughout the study. ResultsThe weight of the patients remained stable, the mean weight before being 65.42 ± 8.35 kg and after completion of the study being 65.42 ± 8.35 kg. There were no changes in the ECG during or after the drug therapy in any of the patients. Group A comprised nine patients, and group B had ten patients. Serum creatinine (mg %) was 0.94 and 0.95, fasting blood sugar mg (%) was 111.05 and 99.63, and postprandial blood sugar (mg %) was 150.89 and 147.94 on pre-treatment and post-treatment, respectively. The mean serum triglyceride levels in group