Prof. Daniel Seifu

Background Chronic kidney disease (CKD), which is characterized by its asymptomatic nature until an end stage, is one of the most common public health problems in the world. Thus, a regular checkup, especially for those individuals with high risk groups is inevitably important, and the screening has been done with laboratory findings. However, in developing countries, including Ethiopia screening for CKD are rarely done, and it is becoming common to hear sudden death from the kidney failure. Therefore, we aimed to screen serum electrolyte levels and estimated glomerular filtration rate (eGFR) among Ethiopian Public Health Institute (EPHI) staff members for an early detection of CKD and to identify the factors associated with it. Methods A cross-sectional study was conducted from July 1 to October 28, 2018 among EPHI staff members. The level of serum creatinine and electrolytes were measured using COBAS 6000 analyzer. Then, eGFR was calculated using MDRD and CKD-EPI equations. Data analysis were done using SPSS version 20, and the factors associated with the outcome variable were assessed using logistic regression. P values < 0.05 were considered as statistically significant. Results This study found that 3.6 and 1.9% of the study participants were at CKD stage II by MDRD and CKD-EPI equations, respectively. Out of the total study participants, 9.5% had hyperkalemia (serum potassium level > 5.0 mmol/L) and 8.5% had hypocalcemia (serum calcium level < 2.15 mmol/L). An older age (P = 0.006), high BMI (P = 0.045) and previous history of CVDs (P = 0.033) were found to be significantly associated factors with reduced glomerular filtration rate. Nine percent of the study participants were obese, 6.1% had family history of kidney failure, 18% self-reported history of hypertension, 3.4% diabetic and 5.3% had CVDs. About 51.2% of the study participants were males, and the majorities, (66%) of the study participants were found to be alcohol consumers. Conclusions The prevalence of a stage II kidney disease was relatively low and none of the participants was under serious kidney disease (GFR < 60 mmol/min/1.73m2). An older age, high BMI and previous history of CVDs were significantly associated with reduced GFR. Hyperkalemia and hypokalemia were the major electrolyte disorders in the study participants.

Chemotherapy-induced hematologic toxicity is the primary reasons of dose reductions and/or delays, low relative dose intensity (RDI), and predicts anticancer response. We investigated the incidence and predictors of chemotherapy-induced hematologic toxicities and reduced RDI in Ethiopian breast cancer patients, and implication of pharmacogenetics variations. Breast cancer patients (n = 249) were enrolled prospectively to receive cyclophosphamide based chemotherapy. Hematological toxicity (neutropenia, anemia, and thrombocytopenia) were monitored throughout chemotherapy cycle. The primary and secondary outcomes were incidence of grade 3 or 4 toxicity and reduced RDI, respectively. CYP2B6∗6, CYP3A5∗3, CYP2C9 (∗2,∗3), CYP2C19 (∗2,∗3), CYP2J2∗7, POR∗28, and ABCB1 (rs3842) genotyping were done. Cox proportional hazard and logistic regression were used to estimate risk predictors of toxicity and reduced RDI, respectively. Majority (73.5%) of the patients were < 45 years of age. The incidence of grade 3 or 4 hematological toxicity was 51.0% (95% CI = 44.54-57.46%). Multivariate Cox proportional hazard regression indicated CYP2J2∗7 genotype [Hazard ratio (HR) = 1.82; 95% CI = 1.14-2.90], pretreatment grade 1 leukopenia (HR = 2.75; 95% CI = 1.47-5.15) or grade 1 or 2 neutropenia (HR = 2.75; 95% CI = 1.73-4.35) as significant predictors of hematologic toxicities. The odds of having hematologic toxicities was lower in CYP2C9∗2 or ∗3 carriers (p = 0.024). The prevalence of reduced RDI was 56.6% (95% CI = 50.3-62.9%). Higher risk of reduced RDI was associated with CYP2J2∗7 allele [Adjusted odds ratio (AOR) = 2.79; 95% CI = 1.21-6.46], BMI ≤ 18.4 kg/m2 (AOR = 5.98; 95% CI = 1.36-26.23), baseline grade 1 leukopenia (AOR = 6.09; 95% CI = 1.24-29.98), and baseline neutropenia (AOR = 3.37; 95% CI = 1.41-8.05). The odds of receiving reduced RDI was lower in patients with CYP2B6 ∗6/∗6 genotype (AOR = 0.19; 95% CI = 0.06-0.77). We report high incidence of chemotherapy-induced hematological toxicities causing larger proportion of patients to receive reduced RDI in Ethiopian breast cancer patients. Patients carrying CYP2J2∗7 allele and low baseline blood counts are at a higher risk for chemotherapy-induced hematologic toxicities and receiving reduced RDI, and may require prior support and close follow up during chemotherapy.

Evaluation of the role of androgen receptor (AR) in the biology of breast cancer is an emerging area of research. There are compelling evidences that AR expression may be used to further refine breast cancer molecular subtyping with prognostic and therapeutic implications. Many studies indicated co-expression of AR with the hormonal receptors in breast cancer has a favorable prognosis. AR is also investigated by many researchers as a potential therapeutic target in treatment of breast cancer. Studies on the frequency and distribution of AR in breast cancer among Africans is barely available. Given the heightened interest to understand its role in breast cancer, we determined AR expression and assessed its association with clinicopathological parameters among Ethiopian women. In this study, 112 newly diagnosed patient with invasive breast cancer at Tikur Anbessa Specialized Hospital were enrolled. Immunohistochemical assessment of AR, ER, PR, Ki67 and HER2 were performed using tissue microarrays (TMA) constructed from their primary tumor block. Out of the 112 participants, 91 (81%) were positive for AR expression and the remaining 21 participants (19%) were negative for AR expression. Expression of AR in ER+, HER2+ and TNBC cases were 93%, 83% and 48% respectively. Our study reveals AR is expressed in a significant number of breast cancers patients and this may indicate that breast cancers cases in Ethiopia have favorable prognosis and could benefit from progresses in AR targeted treatments. Since AR expression has important consequences on the prognosis and treatment of breast cancer, further studies with an increased number of participants is necessary to confirm our reports.

Background: Hyperuricemia is related not only to an increased risk of gouty arthritis but also to an increased risk of cardiovascular diseases, resistant hypertension, insulin resistance and progression of type 2 diabetes mellitus. However, to the best of our knowledge, the prevalence of hyperuricemia and its associated factors have rarely been assessed in Ethiopian populations. Therefore, this study aimed to determine the prevalence of hyperuricemia and its associated factors among adult staff members of the Ethiopian Public Health Institute. Methods: An institution-based cross-sectional study was conducted from July 1 to October 28, 2018. A total of 402 study participants were selected using a simple random sampling technique. An interviewer-administered questionnaire was used to collect the data. A blood sample of approximately 5 mL was collected from each study participant after overnight fasting through standardized methods for biochemical tests, and analyses were carried out with an automated COBAS 6000 analyzer. Data analysis was performed by SPSS version 20 software. The factors associated with the outcome variable were identified by bivariable and multivariable logistic regression analyses, and a p value <0.05 was used to declare statistical significance. Results: The mean age of the study participants was 37.13±10.5 (mean ± SD), and 51.5% of the participants were male. The overall prevalence of hyperuricemia (>5.7 mg/dL for females and >7 mg/dL for males) was found to be 31.0%. The multivariable logistic analysis revealed that age (AOR=1.59, 95% CI 1.01-2.78), sex (AOR=1.66, 95% CI 1.02-2.70), cigarette smoking (AOR=2.05, 95% CI 1.01-4.19) and serum low-density lipoprotein (LDL) (AOR=1.70, 95% CI 1.01-2.87) were significantly associated with hyperuricemia. Conclusion: The prevalence of hyperuricemia was relatively high compared to similar studies. Early screening for hyperuricemia in the general population, especially in those who are smokers, of older age and with high serum LDL levels, is vital to control its adverse effects at an early stage.

Hyperhomocysteinaemia (HHcy) is an independent risk factor for major cardiovascular diseases, but data on the prevalence and predictors of HHcy in low- and middle-income countries like Ethiopia are scant. The aim of this study was to estimate the prevalence of HHcy and associated risk factors in the Ethiopian adult population. A cross-sectional survey on risks of noncommunicable diseases (NCDs) using the STEPwise approach to surveillance (STEPS) survey was conducted between April and June 2015. A total of 4,175 study participants were surveyed. Serum homocysteine (Hcy) and metabolic profile were determined using Cobas Integra 400 Plus and CardioChek PA analyzer, respectively. Factors associated with HHcy were determined using logistic regression. The mean serum tHcy concentration was 14.6 μmol/L, with 16.4 μmol/L in males and 13.4 μmol/L in females. Overall, 38% had HHcy, with figures in males (49%) higher than females (30%). Increased age, being male, and high blood pressure and/or taking blood pressure medication, as well as low consumption of fruit and/or vegetables, were independent risk factors for HHcy. In conclusion, the prevalence of HHcy among the adult Ethiopian population is alarmingly high. Improving diets through the promotion of fruit and vegetable consumption is needed to reduce the risk of NCDs.