Value of therapeutic drug monitoring of endoxifen in Egyptian premenopausal patients with breast cancer given tamoxifen adjuvant therapy: A pilot study.

BACKGROUND: The complex metabolic profile of tamoxifen anticancer drug and polymorphism in its metabolizing enzymes particularly CYP2D6 contribute to the high-observed inter-individual variability in its main active metabolite endoxifen. Therapeutic drug monitoring of endoxifen may play a key role in optimizing tamoxifen therapy, and control of both adverse effects and cancer recurrence. This pilot study aims to assess the clinical benefits of applying endoxifen measurement during tamoxifen therapy in patients with breast cancer. METHODS: Adult premenopausal breast cancer patients ≥ 18 years who received tamoxifen at a fixed dose of 20 mg daily were included. The primary endpoint was to identify the inter-subject variability in serum concentration of the drug and its metabolites especially endoxifen, through fixation of the tamoxifen dose. The secondary endpoint was to check the correlation between endoxifen metabolite concentration and the development of tamoxifen's adverse effects and cancer recurrence. RESULTS: Sixty patients were included in the study with a mean age of 38.4 ± 0.6 years (range: 26-50). The mean concentration of tamoxifen and endoxifen was 181 ± 9.6 ng/mL and 31.49 ng/mL, respectively. The inter-individual variability in concentrations for the drug and its active metabolite as estimated by the coefficient of variation percentage was in 41% and 31%, respectively. Cancer recurrence was observed in a group of patients (n = 16) with an average endoxifen level of 24.48 ng/mL. Another group of patients (n = 25) developed different tamoxifen adverse effects including hot flashes, vaginal bleeding, endometrial thickness, and ovarian cysts with the average endoxifen level of 38.61 ng/mL. The rest of the patients (n = 19) who responded smoothly to the drug with no complications had an average endoxifen level of 31.37 ng/mL. Analysis of variance test showed a significant difference in endoxifen levels between the three groups (p = 0.002). CONCLUSION: The measurement of the endoxifen active metabolite of tamoxifen in breast cancer patients can help dose optimization in light of the observed wide inter-individual variability in drug fixed-dose related concentration of the metabolite. Monitoring of serum concentration of endoxifen can help to reveal, reduce and control tamoxifen's adverse effects and cancer recurrence.

A new grading system for female sexual dysfunction based on the female sexual function index in Egyptian women: a cross-sectional study.

OBJECTIVE: To provide a grading system that accurately reflects the grades of female sexual dysfunction (FSD) severity. PATIENTS AND METHODS: A cross-sectional study was conducted in Assiut University Hospital. It included 500 women who answered the Arabic version of the Female Sexual Function Index (FSFI) after getting their consent. A gradient of FSD severity was created, classifying FSD into five grades: severe, moderate, mild to moderate, mild, and no FSD. RESULTS: According to our grading system, FSD was detected in 339 women (67.8 %); Mild FSD in 20.4%, mild to moderate in 41.6%, moderate in 15.3%, and severe in 22.7%. Mean scores of desire show a linear trend of reduction from 3.8 in mild to 3.36 in mild to moderate to 2.25 in moderate and markedly reduced to 2.1 in severe grade. This difference was highly statistically significant (p= 0.002). The same was reported in arousal, orgasm, and satisfaction domains, while in lubrication and pain domains, the difference was not statistically significant. CONCLUSION: In this study, our grading system was complementary to the FSFI. Moreover, it seems to be more practical and useful in grading the severity of FSD.

Prevalence and factors associated with warts in primary school children in Tema District, Sohag Governorate, Egypt.

BACKGROUND: Warts are one of the most common, persistent, and frustrating cutaneous problems encountered in dermatology clinical practice especially in younger generations. OBJECTIVE: To determine the prevalence of warts in primary school children in Tema District, Sohag, Egypt, and to determine possible factors associated with transmission. PARTICIPANTS AND METHODS: A school-based cross-sectional (prevalence) study was carried out during the academic year 2015-2016 in six primary schools in Tema District, Sohag Governorate, Egypt. A total of 1045 students were examined. Data was collected using a self-administered semi-structured questionnaire which was taken home by the student to be completed by his/her caregiver. RESULTS: Among 1045 examined school students, 108 students were diagnosed as having warts with a prevalence rate of 10.3%. Common wart was the most common type among students (49.0%) followed by plantar and plane warts (24.1%, each) while genital wart was the least one (2.8%). There was no significant sex or age difference. The prevalence of warts was significantly higher among students from public schools, rural areas, and big families; students with lower paternal education level; and students who were sharing shoes, walking barefoot, having contact with house pets, or exposed to water channels. CONCLUSION: Warts, especially the common variant, are highly prevalent in primary school children. The significant factors associated with the development of warts in these children were big family size and sharing shoes. Other significant associated factors included living in rural areas, attending public schools, illiterate parents, fathers with manual work, and swimming in water canals.

Prevalence and predictors of occult hepatitis C virus infection among Egyptian patients who achieved sustained virologic response to sofosbuvir/daclatasvir therapy: a multi-center study.

BACKGROUND: Occult hepatitis C virus (HCV) infection (OCI) is characterized by the detection of HCV-RNA in non-serum reservoirs, such as peripheral blood mononuclear cells (PBMCs) and/or hepatocytes with undetectable HCV-RNA or antibodies in the serum. In this study, we tried to evaluate the prevalence and possible predictors of OCI in patients who achieved sustained virologic response (SVR) post sofosbuvir/daclatasvir (SOF/DCV) therapy. PATIENTS AND METHODS: A cross-sectional multicenter study was designed to enroll 1,280 HCV-infected patients who received SOF (400 mg) plus DCV (60 mg) once daily ± ribavirin regimen for 12 weeks and achieved SVR 12 weeks post treatment. They were randomly recruited from three dedicated Egyptian centers for management of HCV. Real-time PCR was performed to detect HCV-RNA in serum and PBMCs and to evaluate the different risk factors pertaining to the existence of OCI. RESULTS: HCV-RNA was detected in PBMCs of 50 (3.9%) of them. All OCI cases exhibited significant fibrosis score and raised pre-treatment alanine aminotransferase (ALT) levels. Logistic regression analysis comparing OCI with non-OCI revealed that high pre-treatment viral load, raised ALT, advanced fibrosis score, prolonged prothrombin time, low albumin, Child B score, antiviral experienced patients, and raised bilirubin are the most significant predictor for the possibility of OCI presence with Odds Ratio as 7.03, 5.13, 4.4, 2.68, 2.52, 1.9, 1.5, and 1.2, respectively. CONCLUSION: In spite of its remote possibility, OCI post SOF/DCV therapy may be present in some cases, and this may entail a re-auditing for the definition of SVR by dual testing in both serum and PBMCs.

Lower Transcranial Doppler Flow Velocities in Sickle Cell Anemia Patients on Hydroxyurea: Myth or Fact.

Transcranial Doppler (TCD) detects stroke risk in patients with sickle cell anemia (SCA). Hydroxyurea therapy has the ability to induce increased levels of fetal hemoglobin in sickle cells thus decreasing tendency for red cell sickling. This study aimed to evaluate TCD findings in SCA patients on hydroxyurea and correlate the time-averaged mean velocity (TAMV) with their hematological parameters. Forty SCA patients of both sexes, aged 16-22 years with no history of stroke were screened with TCD for an elevated TAMV, divided into: Group T (20 patients on blood transfusion); and Group H (20 patients on daily hydroxyurea). For all, full medical history, clinical examination, hemoglobin, hematocrit, leukocytes, platelets, fetal hemoglobin and sickling test, in addition TCD to describe the pattern of cerebral blood flow abnormalities were done. TAMV in all cerebral arteries were significantly higher in Group T than Group H, the highest TAMV (147.5 ± 57.09 cm/s) was found in the right middle cerebral artery and correlated negatively with hematocrit in Groups H (P < 0.001). There were 2 (10%) abnormal TAMV results and 5 (25%) conditional in Group T, while all results were normal in Group H. Hydroxyurea therapy may lower TCD velocities and prevent the risk of primary stroke in SCA patients.

Effect of female genital mutilation/cutting; types I and II on sexual function: case-controlled study.

BACKGROUND: The existing literature is contradictory regarding effects of female genital mutilation/cutting (FGM/C) on sexual functions. The aim of this study was to explore the impact of type I and II FGM/C on sexual function of Egyptian women. METHODS: We recruited 197 cut women and 197 control women from those visiting Assiut University hospitals for different reasons. We asked each woman to fill the Arabic female sexual function index (FSFI) (a self reported 19-item questionnaire assessing the main domains of female sexual function). Genital Examination was done to confirm the type of FGM. RESULTS: Female sexual dysfunction (FSD) was found in 83.8% of FGM/C cases in contrast to 64.5% of the control. The total FSFI score in the FGM/C group (19.82 ± 7.1) was significantly lower than in the control group (23.34 ± 8.1). Concerning the types of FGM/C, type 73.6% of cases had type I and 26.4% had type II. Type I FGM/C was performed mainly by physicians (62.1%) while type II was performed mainly by midwives (44.4%). FSD was found in 83.4% of FGM/C I cases and in 84.6% of FGM/C II cases. There was no statistically significant difference between the two types of FGM/C as regards total and individual domain scores except for the pain domain. There were significantly lower total and individual domain scores in both FGM/C types except for the desire domain compared to control. CONCLUSION: In this study, FGM/C was associated with reduced scores of FSFI on all domains scores, and among both types I and II, both were associated with sexual dysfunction.

Could intradialytic nutrition improve refractory anaemia in patients undergoing haemodialysis?

BACKGROUND: This prospective randomised study was designed to evaluate the efficacy of intradialytic parenteral nutrition (IDPN) therapy in malnourished patients with refractory anaemia. METHODS: Forty patients who were malnourished with a BMI not greater than 23 (17-23) kg/m2 , undergoing regular HD were included. Of those, 20 patients received 500-1000 ml of IDPN at a rate of 250-300 ml/h at each HD session three days per week for six consecutive months. The other 20 patients did not receive IDPN infusion. The malnutrition inflammation score (MIS) and haematological parameters were recorded at baseline and after three and six months. RESULTS: Mean haemoglobin levels, BMI and serum albumin were significantly increased while MIS was significantly decreased after the 3rd and 6th months of IDPN. CONCLUSION: IDPN has a good role in improving refractory anaemia by significantly increasing haemoglobin levels, body weight, and serum albumin levels. The intervention also significantly decreases the MIS of patients.

Obesity risk prediction among women of Upper Egypt: The impact of serum vaspin and vaspin rs2236242 gene polymorphism.

BACKGROUND: Vaspin is an adipokine that is potentially linking obesity, insulin resistance, metabolic syndrome and type-2 diabetes. AIM: The present study aimed to investigate the impact of vaspin rs2236242 gene polymorphism on the risk of obesity, diabetes, their metabolic traits, and serum vaspin levels in a sample of Upper Egyptian women. SUBJECTS AND METHODS: A total of 224 subjects, 112 obese (62 non diabetics, 50 diabetics) and 112 controls were included in this case control study. Vaspin gene rs2236242 polymorphism was performed using tetra-amplification refractory mutation system-polymerase chain reaction (T-ARMS-PCR) and serum vaspin levels were estimated by ELISA. RESULTS: The minor (A) allele of vaspin rs2236242 gene polymorphism was significantly lower in obese (30.8%) than controls (43.7%) (P=0.005). The protective effect was evident in dominant and recessive inheritance models (TT vs TA+AA, P=0.004 and TT+TA vs AA, P=0.036). After adjusting genotypes for diabetes there were no significant association between vaspin rs2236242 gene polymorphism and obesity but significant association was maintained in the obese diabetics. Vaspin serum levels were found to be lower in minor protective (AA) genotype carriers than the other two genotypes (P<0.001). In the mean-time serum vaspin levels were significantly higher in obese diabetics and non-diabetics than controls (P<0.001 each).There were significant positive correlations between vaspin levels and hs-CRP, cholesterol, LDL-C, fasting glucose, HOMA-IR, insulin, and ALT values (P<0.05 each) and a negative correlation with HDL-C (P<0.01). CONCLUSION: The minor A allele of vaspin rs2236242 polymorphism plays a protective role against obesity and diabetes but this relation is largely ascribed to its effect on insulin resistance. The serum vaspin concentration was lower in minor protective allele carriers. To the best of our knowledge, this is the first study of vaspin SNP in Upper Egyptian women. The entire understanding of vaspin intimate mechanistic action might enable the development of novel etiology-based treatment strategies for obesity, the complex genetic trait.

Study of the impact of viral load of hepatitis C on patients with concomitant psoriasis vulgaris.

BACKGROUND AND STUDY AIM: Concomitant hepatitis C virus (HCV) infection and psoriasis vulgaris (PV) are not uncommon coexisting diseases, especially in areas with high viral hepatitis endemicity. To date, data about the interaction between both diseases are scarce. Therefore, we aimed to describe the possible interplay between the HCV viral load and psoriatic activity in concomitant Egyptian diseased patients. PATIENTS AND METHODS: Between December 2011 and August 2013, all psoriatic patients attending Assiut University Hospital outpatient clinics were tested for HCV serologic assay. Patients with positively coexisting diseases were further reevaluated for psoriasis area severity index (PASI) score assessment, liver function tests, HCV-RNA-polymerase chain reaction (PCR) assays, and sonographic examination of the liver. For comparative purposes, another matched group (n=26) with psoriasis only (HCV-negative group) was enrolled as a control. RESULTS: During the period of the study, 20 patients with concomitant PV and HCV infection (HCV-positive group; 50% males, mean age of 44.15±10.66 years) were recruited. The mean PASI score was 44.75±10.38 and clinical signs of liver dysfunction were observed in 40% (n=8), 100% had abnormal liver function tests (n=20), and 75% had sonographic findings of cirrhosis (n=15). The PASI score was significantly higher in the HCV-positive psoriatic group compared to the HCV-negative control (p<0.001). Significant correlations were detected between the PASI score and the viral loads, and also with alanine aminotransferase (ALT). CONCLUSION: When HCV was found concomitantly with PV, a high possibility of severe disease pattern will be expected that entails special precautions in the treatment process.

Sensitivity and specificity of ultrasonography in predicting etiology of azoospermia.

OBJECTIVE: To determine the sensitivity and specificity of different ultrasound (US) modalities in predicting an obstructive vs a nonobstructive etiology of azoospermia. MATERIALS AND METHODS: A total of 268 azoospermic men with available histopathologic slides were separated into obstructive (n = 104) and nonobstructive (n = 164) groups. Scrotal US studies, including color Doppler and transrectal US examinations, were performed in all patients and compared with the testicular biopsy results as the reference standard. RESULTS: We found that a decreased testicular volume and intra- and extratesticular varicocele were the most common abnormalities detected using scrotal US in those with nonobstructive azoospermia. In contrast, epididymitis, spermatocele, and duct ectasia were the most common findings in those with obstructive azoospermia. The sensitivity and specificity of scrotal US in detecting nonobstructive azoospermia was 75% and 72%, respectively, and for detecting obstructive azoospermia was 29.8% and 87%, respectively. Prostatic midline cysts, ejaculatory duct calcification, dilated seminal vesicle, and/or vassal ampullae were the most common abnormalities detected using transrectal US for obstructive azoospermia. The sensitivity and specificity of transrectal US in detecting obstructive etiology was 45% and 83%, respectively, and for functional etiology was 39% and 88%, respectively. CONCLUSION: Scrotal US was more sensitive in detecting functional azoospermia and more specific in detecting obstructive azoospermia. However, transrectal US was more sensitive in detecting obstructive azoospermia and more specific in detecting functional azoospermia. Both tests had greater specificity than sensitivity for obstructive azoospermia, indicating that US has the ability to exclude more than to diagnose cases of obstructive azoospermia. However, US is unlikely to completely replace testicular biopsy.

Correlation between seminal lead and cadmium and seminal parameters in idiopathic oligoasthenozoospermic males.

INTRODUCTION: The exact causes of the decline in semen quality are not yet known, environmental factors have been considered to play an important role. Lead (Pb) and Cadmium (Cd) are two of the well-known reproductive toxicants to which humans are exposed occupationally and environmentally and can lead to negative effects on the testicular functions. The aim of this study was to evaluate lead and cadmium levels in seminal plasma of men with idiopathic oligoasthenozoospermia in comparison to fertile healthy controls and to correlate these levels with conventional semen parameters, sperm hypo-osmotic swelling (HOS) percentage, sperm DNA fragmentation percentage, and semen reactive oxygen species (ROS) levels. MATERIAL AND METHODS: Thirty infertile male patients with idiopathic oligo and/or asthenozoospermia and thirty healthy fertile men, which was the control group, were included in the study. Lead and cadmium levels in seminal plasma, semen parameters, sperm HOS, sperm DNA fragmentation percentage and semen ROS assay were measured in all subjects. RESULTS: There was a significant increase in seminal lead and cadmium levels among infertile males in comparison to controls. There were significant negative correlations between seminal lead and cadmium levels on one hand and certain semen parameters especially progressive sperm motility and vitality (HOS). Importantly, significant positive correlations were noted between seminal lead and cadmium levels on one hand and sperm DNA fragmentation percentage and semen ROS level in infertile men and controls on the other hand. CONCLUSIONS: Thus, men with idiopathic male infertility had higher levels of lead and cadmium in their semen which correlated with impairment of sperm motility and vitality percentages and more importantly with higher sperm DNA fragmentation% and semen ROS level.

Virologic and histologic characterisation of dual hepatitis B and C co-infection in Egyptian patients.

BACKGROUND AND STUDY AIMS: Data about dual hepatitis C (HCV) and B (HBV) co-infection are still scarce, especially in endemic areas such as Egypt. Therefore, we aimed to characterise the virologic and histologic pattern of dual B/C co-infection in a tertiary care centre in Egypt. PATIENTS AND METHODS: After obtaining approval from the review board, a retrospective design to evaluate the data registry between January 2009 and December 2012 of patients with dual HCV and HBV seropositivity (BC-group) at the Viral Hepatitis Unit in Ministry of Health and Assiut University Hospital, Egypt was conducted. Data for hepatitis B e antigen (HBe-Ag) and anti-HB core status, anti-hepatitis delta virus (anti-HDV), HBV-DNA and HCV-RNA assays and liver biopsy (METAVIR scoring) results were collected. Two other matched groups of mono-HCV (C-group) and HBV (B-group) were selected as controls. All patients were naive for antiviral therapy. RESULTS: A total of 3300 patients were enrolled. Dual infection was observed in 25 (0.7%) patients (all males, mean=35.2±10.2years). Four patients (16%) were HBe-Ag-positive. Six (24%) patients were HBV-DNA-negative and all were positive for HCV RNA. Between groups, raised alanine aminotransferase (ALT) was found in 76%, 41.7% and 49.2% of the BC, B and C groups, respectively (p=0.023). HBV DNA >2000IUml(-1) was more in the B-group than in the BC-group (63.9% vs. 36%; p=0.042) and HCV RNA >800,000IUml(-1) was more in the BC-group than in the C-group (28% vs. 12.3%; p=0.009). Histologically, there is no statistical significant difference between the three groups. CONCLUSION: Dual hepatitis B/C infection is not uncommon and their virologic and histologic profile is modest. Further evaluation with regard to treatment and long-term follow-up is warranted.

Defining patient selection for prostate-sparing cystectomy in squamous cell carcinoma of the urinary bladder associated with bilharziasis: an overview of 236 patients.

OBJECTIVE: To determine possible risk factors associated with prostate invasion in patients with squamous cell carcinoma (SCC) of the urinary bladder associated with bilharziasis. METHODS: After obtaining approval from the medical ethics committee, we reviewed the clinical and pathologic data from 236 male patients in our department between January 2006 and October 2010 who were treated with radical cystoprostatectomy and proved to have SCC associated with bilharziasis. We reviewed the clinical and histopathologic data regarding prostate infiltration from SCC of the urinary bladder associated with bilharziasis. RESULTS: Two-hundred thirty-six patients were included in this study. Prostate infiltration was present in 14 patients (5.9%). Tumor located in the bladder neck (P = .000001), tumors >5 cm (P = .009), and advanced clinical tumor stage (P = .000001) were associated with highly statistically significant increased risk of prostate invasion from SCC of the urinary bladder. Different patients' ages, high tumor grade, and regional lymph nodes' metastasis were not associated with increased risk of prostate invasion from SCC of the urinary bladder. CONCLUSION: Prostate infiltration from SCC of the urinary bladder (which is associated with bilharziasis) is not uncommon. Tumor >5 cm, bladder neck tumor, and high clinical tumor stages should be considered at least relative contraindications for prostate-sparing cystectomy.