Two mutations (C228T and C250T) in the promoter region of the telomerase reverse transcriptase (TERT) have recently been described in different types of cancer including follicular cell-derived thyroid cancer (TC). In this paper, we reviewed the rates of these mutations in different types and subtypes of TC, their association with a number of clinical and histopathological features and outcome of TC, and their potential diagnostic and prognostic roles in TC. The overall rate of these mutations in TC is about 14 % with least prevalence in the well-differentiated subtypes of papillary thyroid cancer (10-13 %). Their rates increase significantly with increasing aggressiveness of TC reaching about 40 % in the undifferentiated and anaplastic thyroid cancers. There is also clear association with increasing age of patients at the time of diagnosis of TC. The evidence is compelling but with some conflicting results for associations between TERT promoter mutations and tumor size, extrathyroidal invasion, distant metastases, high tumor TNM stage, BRAF (V600E) mutation, recurrence, and mortality. A couple of studies reported a potential diagnostic role for TERT promoter mutations in thyroid nodules with indeterminate cytology of fine needle aspiration biopsy. These studies showed 100 % specificity but very low sensitivity of 7-10 %. The sensitivity increases significantly when TERT promoter mutation testing is combined with other gene mutations, particularly BRAF (V600E) and RAS mutations. Although TERT promoter mutations seem to play significant roles in the pathogenesis of TC, the mechanisms by which they contribute to carcinogenesis remain elusive and future work is needed to fully assess the roles, interactions, and impact of these mutations on the pathogenesis, diagnosis, prognosis, and therapeutics of TC.

e17591 Background: Sodium iodide (I-131) is eliminated predominantly through renal clearance. There is no consensus on the ideal dose of I-131 to be administered for patients with impaired kidney function. We aim to compare the rate of I-131 clearance in patients with impaired to those with normal renal functions. Methods: 27 cases (34 treatments) of differentiated thyroid cancer and eGFR 15-59 ml/min/1.73 m2 received I-131 (mean dose of 150 mCi) for remnant ablation between 2010 and 2016. Another 34 patients matched for age, gender, weight and I-131 dose with eGFR ≥ 60 ml/min/1.73 m2 were selected as controls. Endpoints of interest were (a) Length of hospital stay (LOHS) until the patient’s I-131 activity declines to < 30 mCi (b) Exposure rate measured by Geiger counter 0 to 48 hours after treatments (ER 48). Paired t-test was used to compare both groups. Results: Mean LOHS for cases vs. controls was 2.47 vs. 2 days respectively (P = 0.007). Results of ER 48 were available and matched in 18 cases and controls. Mean ER 48 for cases vs. controls was 3.74 vs. 1.8 mR/h respectively (P = 0.002). The mean proportional reduction of exposure rate after 48 hours compared to hour 0 for cases and controls was (-88% vs. -92.6%, P = 0.008), (-93.5% vs. -94.5%, P = 0.5) and (-67.2% vs. 94.3%, P = 0.04) for eGFR 46-59 (n = 13), 30-45 (n = 3) and 15-29 ml/min/1.73m2 (n = 2) respectively. Conclusions: Patients with impaired renal function are subject to longer hospital stay and delayed renal clearance of the tracer with consequent increased radiation exposure. Guidelines should consider adjusting the dose of I-131 in these patients to avoid possible harmful effects of excess I-131 on vital organs.

How to cite this article: Zekri J, Farag K, Al-Saadi R, Ashour M, Haggag R. Safety and efficacy of biweekly cetuximabbased chemotherapy for patients with metastatic colorectal cancer. J Unexplored Med Data 2016;1:15-20. Aim:Cetuximab was administered weekly in registration clinical trials. Biweekly administration is more convenient when combining cetuximab with biweekly chemotherapy in patients with metastatic colorectal cancer (mCRC). The aim of this study is to evaluate safety and efficacy of biweekly cetuximab at a dose of 500 mg/m 2 with chemotherapy in routine clinical practice. Methods: Clinical data of 19 consecutive patients with K-RAS wild type mCRC who received biweekly cetuximab with biweekly fluropyrimidine based chemotherapy were reviewed. Toxicity assessment was limited to the first 6 cycles of treatment. Best tumor response was assessed by an independent radiologist. Results: Median age was 59 (24-74) years. Cetuximab was administered in first, second and third line settings in 7, 9 and 3 patients respectively. Grade I/II cetuximab specific adverse events (AEs) were skin rash (47.3%), diarrhea (21%), infusion reactions (10.5%), Hypomagnesaemia (10.5%) and nail disorders (5%). Grade III AEs were skin rash (10.5%) and diarrhea (5.3%). There was no grade IV AEs. There were no complete responders. Partial response was achieved in 8 (42.1%) and stable disease in 6 (31.5%) patients. Conclusion: This small but real life experience shows that biweekly cetuximab with chemotherapy is safe and effective. The frequency of AEs compares favorably to weekly administration reported in the literature. These finding add to the relatively limited available data on biweekly administration to support its adoption in routine clinical practice. ABSTRACT

Purpose High-dose chemotherapy (HDCT) and autologous stem cell transplantation (ASCT) is used to treat patients with relapsed Hodgkin's lymphoma. In this retrospective study we report our experience with patients who underwent HDCT and ASCT. Methods All patients ≥15 years old with relapsed/refractory Hodgkin's lymphoma who underwent HDCT and ASCT between June 2001 and December 2013 were included. Results Fifty-four patients were identified. Median age at transplant was 22 years (range 15-49 years); 26 were men and 28 were women. Forty-eight patients (89%) underwent HDCT and ASCT after achieving a radiological response to salvage chemotherapy. The rate of radiological complete response to salvage chemotherapy was 13% and reached 50% within 3 months of ASCT in assessable patients. After a median follow-up of 25 months, 31 patients (57%) were still alive with no evidence of relapse or progression. Median event-free survival (EFS) was 24 months (95% CI 8.7-39.3) and 3-year EFS was 56%. Median overall survival (OS) was not reached and 3-year OS was 82.5%. Bulky mediastinal disease at relapse, hemoglobin level, and number of salvage regimens did not significantly impact EFS in univariate and multivariate analyses. After transplantation there was a trend towards longer EFS (30 vs. 24 months; p = 0.36) in patients with a longer time from the end of first-line treatment until relapse (≥12 vs. <12 months). The 100-day transplant-related mortality was 5.5%. Conclusions HDCT and ASCT for relapsed/refractory Hodgkin's lymphoma is safe. Our findings are consistent with published phase III results. Longer follow-up is warranted.

Introduction: Metronidazole has been prescribed to treat infections for over a century and continues to be helpful in the therapy of amoebiasis, trichomoniasis, and giardiasis. Metronidazole is a cost-effective medication because of its low price, few adverse effects, and favorable pharmacokinetic and pharmacodynamic properties; nevertheless, it interacts with a wide variety of other medications. Some interactions with other medicines diminish its effectiveness, while others increase it. Aims: The study aims to detect and evaluate metronidazole interactions with other medicines at King Abdulaziz Specialist Hospital. Methodology: This retrospective study encompasses the review of 360 computerized prescriptions inside the outpatient clinic at King Abdulaziz Specialist Hospital in Saudi Arabia between March and September 2020 to detect and evaluate interactions among metronidazole and different medications. Results: Metronidazole interactions are mostly major or moderate. Metronidazole had the most common interactions with domperidone (15.83 %), famotidine (13.89 %), and ciprofloxacin (11.67 %). Metronidazole contains a nitroimidazole ring, which suppresses the metabolism in the liver of numerous medications, including those that may be metabolized by the CYP3A4 and/or CYP450 2C9 isoenzymes. The combination of metronidazole with phenytoin or phenobarbital can cause metronidazole elimination to be accelerated and phenytoin clearance to be reduced. Metronidazole may improve warfarin's anticoagulant effects, leading to a longer prothrombin time and a higher risk of bleeding. Concurrent use of metronidazole with alfuzosin, escitalopram, and ondansetron may raise the risks of QT-interval prolongation and arrhythmias. Conclusion: Most metronidazole drug interactions can be avoided by following excellent clinical care and clinical pharmacology concepts, such as avoiding complex treatment regimens, educating patients. and identifying patient risk factors. Furthermore, before prescribing and dispensing medicines, physicians and pharmacists should utilize drug-drug interactions checkers such as Micromedex and Lexicomp or a book such as Stockley's Drug Interactions.