Severe Behçet's disease equally affects both genders in Egyptian patients: A multicentre retrospective follow-up study.

Behçet's disease is a relapsing multisystemic disease. Its highest prevalence is seen along the Silk Road. While several studies reported gender disparities, others didn't. Scarce data are available about the Arabs and the gender differences detected in some ethnicities could not be applied to others. Our study aimed to detect gender differences among a cohort of adult Egyptian patients with Behçet's disease. Medical files of 255 adult patients diagnosed with Behçet's disease at the Rheumatology and Rehabilitation Department of Kasr Al-Aini Hospital, Cairo University and the Internal Medicine Department of Tanta University, between 2002 and 2018, were retrospectively reviewed. The demographic features, the cumulative clinical features, the use, if any, of an intravenous pulse of methylprednisolone and immunosuppressive/biological drugs, and the frequency of the cumulative damage to the different organ systems were described. The disease severity score was calculated as well. The study revealed a prominent male predominance; the male to female ratio was 6.7:1. Acne/pseudofolliculitis was more common in males (28.6% vs 13.2%, p=0.046); the same was observed regarding any vascular involvement and peripheral venous disease (36.3% vs 18.4%, p=0.03 and 30.4% vs 13.2%, p=0.03, respectively). On the other hand, encephalitis and cranial nerve lesions were more prevalent in females (15.8% vs 6%, p=0.03 and 10.5% vs 3.2%, p=0.04, respectively). Severe Behçet's disease equally affects Egyptian males and females. BD should not be considered a benign disease in Egyptian females. The same quality of medical care should be equally offered to both genders.

Pregnancy outcome in women with active and inactive lupus nephritis: A prospective cohort study.

Several studies have emphasized poor pregnancy outcomes associated with active lupus nephritis at the onset of conception. A few controversial studies have compared pregnancy outcome in patients with inactive lupus nephritis at conception and those without a history of lupus nephritis. This study aimed to find out if quiescent lupus nephritis at the onset of conception carries an increased risk of pregnancy complications compared to pregnancies without a history of lupus nephritis. This is a prospective cohort study carried out at the Rheumatology/Obstetrics Conjoint Clinic of Kasr Al-Ainy Hospital between January 2006 and December 2017. A total of 119 pregnancies were included: 72 pregnancies in group I (with a history of lupus nephritis) and 47 pregnancies in group II (non-renal systemic lupus erythematosus). They were subjected to full history taking, monthly clinical examination and laboratory investigations. In total, 16 (22.2%) renal pregnancies had renal flares at the onset of conception. Maternal complications, specifically renal flares, were reported in 36 (50%) pregnancies in group I and 13 (27.7) pregnancies in group II, with a significant difference (p = 0.015). No significant differences were found concerning the frequency of pregnancy-related maternal and fetal complications between the two groups. When data were re-analyzed after excluding patients experiencing renal flares during the 6 months preceding pregnancy, there were no significant differences regarding the frequency of maternal and fetal complications between renal and non-renal pregnancies. In conclusion, lupus nephritis, per se, is not a risk factor for poor pregnancy outcome; rather, it is the lupus nephritis activity at the onset of pregnancy.

The adverse effects of interferon-free regimens in 149 816 chronic hepatitis C treated Egyptian patients.

BACKGROUND: Interferon-free regimens are associated with high sustained virological response; however, associated adverse effects have yet to be fully reported. AIM: To evaluate the adverse effects associated with the different direct-acting antiviral drug (DAA) regimens in Egyptian patients. METHODS: This multicenter retrospective study included all adverse effects during and after treatment with DAA regimens of 149 816 chronic hepatitis C treated Egyptian patients. Patients received sofosbuvir (SOF)/ribavirin (RBV) (n = 21 835), SOF/simeprevir (n = 24 215) SOF/daclatasvir (DCV) (n = 58 477), SOF/DCV/RBV (n = 45 188) and paritaprevir/ombitasvir/ritonavir/RBV (n = 101). The duration of treatment varied between 12 and 24 weeks. All changes in the treatment regimens, discontinuation, mortality, and serious side effects were reported. RESULTS: Adverse effects developed in 2475 (1.7%) (mean age [54 ± 9], male gender [53%]) patients. Serious side effects developed in 68% of these patients, and SOF/RBV was the most common causing regimen (73%, P < 0.001). Anaemia and hyperbilirubinemia were the most common side effects (731/149816, 0.5% and 463/149816, 0.3%, respectively) and SOF/RBV (588/21835, 3% and 353/21835, 1.6%, respectively) showed the highest incidence in the treated patients. Hepatocellular carcinoma and mortality were reported in 0.02% and 0.06% of all treated patients, respectively. Patients with liver cirrhosis showed higher incidence of serious side effects (Log rank P = 0.045) and mortality (Log rank P = 0.025) than patients without liver cirrhosis. Male gender (P = 0.012), lower haemoglobin (P < 0.001), platelets (P < 0.001) and albumin (P = 0.001), higher bilirubin (P = 0.002) and cirrhosis (P < 0.001) were factors associated with serious side effects development. CONCLUSION: Adverse effects associated with DAAs are few, anaemia being the most common. SOF/RBV regimen showed the highest rate of side effects while SOF/DCV showed the least.

Characteristics of systemic lupus erythematosus in a sample of the Egyptian population: a retrospective cohort of 1109 patients from a single center.

Introduction Systemic lupus erythematosus (SLE) is a multisystem autoimmune disease that can vary among different ethnic and racial groups. Objective The objective of this paper is to study the prevalence of various manifestations of SLE in a sample of the Egyptian population. Patients and methods Information in this study was derived from the medical records of SLE patients who sought medical advice at a private clinic in Cairo from January 1980 to June 2016. Results This study included 1109 SLE patients, of whom 114 (10.3%) were males and 995 were females (89.7%). Mean age of onset was 25.89 ± 10.81 years, while the median of disease duration from the onset of the disease till the last recorded visit was 26 months. The most common cumulative manifestations were arthritis (76.7%), malar rash (48.5%), leukopenia (45.7%), and photosensitivity (45.6%). A total of 33.1% of the patients had nephritis, and neuropsychiatric lupus was present in 6.4% of the patients. Secondary antiphospholipid syndrome was present in 11.5% of the patients. Antinuclear antibody and anti-double-stranded deoxyribonucleic acid were present in 1060/1094 (96.9%) and 842/1062 (79.3%) of the patients, respectively. Antiphospholipid antibodies were present in 266/636 (41.8%) of the patients, anti-Smith in 54/240 (22.5%), anti-SSA/Ro in 61/229 (20.4%), and anti-SSB/La in 32/277 (11.6%) of the patients. Male patients had a statistically higher prevalence of nephritis ( p = 0.01), whereas arthritis and alopecia were statistically higher in females ( p = 0.012 and p = 0.006, respectively). Patients with juvenile onset had a statistically higher prevalence of nephritis and seizures ( p < 0.001 and p = 0.012, respectively). Conclusions Arthritis and malar rash represented the most common clinical manifestations. Male and juvenile-onset patients had a predilection toward a more severe disease. These results are in agreement with many studies conducted in the Middle East and worldwide. On the other hand, major organ involvement was exceptionally low, which is contradictory to several reports from the Middle East and across the globe.

The effectiveness and safety of ledipasvir plus sofosbuvir in adolescents with chronic hepatitis C virus genotype 4 infection: a real-world experience.

BACKGROUND: The combination of ledipasvir plus sofosbuvir was recently approved for treatment of adolescent (12-17 years) HCV genotype 1, 4, 5 & 6 patients. However, few clinical trials have been performed in genotype 1 patients. AIM: To investigate the effectiveness and safety of ledipasvir plus sofosbuvir in chronic HCV adolescent patients with genotype 4 in the real world. METHODS: This prospective multicentre (six centres) open-label study included 144 adolescent chronic HCV patients with genotype 4 (mean age 14 ± 2, 69% males). All patients received a combination tablet containing 400 mg sofosbuvir and 90 mg ledipasvir once daily for 12 weeks. Laboratory and virological markers were evaluated at baseline, week 4, week 8 and week 12 (EOT), and 12 weeks after end of treatment (SVR12). RESULTS: SVR12 was observed in 142/144 patients (99%). The relapsers occurred in previous naïve patients (n = 2/128, 2%), while the experienced patients showed 100% SVR12. SVR12 was 98% in F0/F1 patients in comparison to 100% in F2 patients (P = 0.552). No serious side effects were observed, nor was treatment discontinuation or death. Headache was the most common side effect in all patients (20%). In experienced patients, pruritus (31%, P = 0.007), diarrhoea (44%, P < 0.001) and skin rash (19%, P = 0.002) were higher than in naïve patients. CONCLUSIONS: A ledipasvir plus sofosbuvir regimen is well tolerated and effective, and can be used safely in treating adolescent patients with chronic hepatitis C genotype 4.

Liver stiffness measurement using acoustic radiation force impulse elastography in overweight and obese patients.

BACKGROUND: Obesity and overweight are global health problems. AIM: To evaluate the diagnostic accuracy of liver stiffness measurement (LSM) using acoustic radiation force impulse (ARFI) elastography in overweight and obese patients for staging liver fibrosis. METHODS: Ninety-seven patients (mean age: 50 years, 50% male) with body mass index (BMI) ≥25 kg/m(2) (mean BMI: 31 kg/m(2) ) were prospectively enrolled. All patients underwent ARFI elastography and liver biopsy. In 87/97 patients, transient elastography (TE) was performed (M- and XL-probes). Patients were divided into two groups respectively: overweight: BMI <30 kg/m(2) (n = 61); and obese: BMI ≥30 kg/m(2) (n = 26). RESULTS: Acoustic radiation force impulse elastography correlated with liver fibrosis in overweight (r = 0.84, P < 0.0001) and obese patients (r = 0.85, P < 0.0001), while no correlation was observed with steatosis, steatohepatitis and BMI. Area under the curve detecting liver cirrhosis for ARFI and TE were 0.97 in overweight and 0.94 and 0.92 in obese patients. In both groups, the failure rate was lower for ARFI than TE. ARFI of liver segment 8 showed a lower discordance than TE in both groups (overweight: 3% vs. 12%, P = 0.002; obese: 8% vs. 27%, P = 0.034). Steatosis and steatohepatitis were neither predictors of discordance nor of performance in LSM by ARFI or TE in both groups. CONCLUSIONS: In overweight and obese patients, acoustic radiation force impulse can diagnose liver cirrhosis and significant fibrosis with high diagnostic accuracy. Liver stiffness measurement using the XL-probe reduces the influence of BMI, steatosis and steatohepatitis. The failure and discordance rates were lower for acoustic radiation force impulse than transient elastography in both patients groups.

Evaluation of Liver and Spleen Stiffness with Acoustic Radiation Force Impulse Quantification Elastography for Diagnosing Clinically Significant Portal Hypertension.

PURPOSE: Hepatic vein pressure gradient (HVPG) is the gold standard for diagnosing clinically significant portal hypertension (CSPH). The aim of this study was to investigate-in comparison to HVPG-the ability to diagnose CSPH by liver and spleen stiffness measurements obtained by acoustic radiation force impulse (ARFI) imaging. MATERIALS AND METHODS: A total of 78 patients (mean age: 53 ±â€Š13 years, 62 % male) with chronic liver disease were enrolled in this study. Each patient received liver (LSM) and spleen (SSM) stiffness measurements by ARFI, an HVPG measurement and a transjugular liver biopsy on the same day. Patients were classified according to their HVPG into three different groups: HVPG < 10 mmHg, HVPG ≥ 10-< 12 mmHg and HVPG ≥ 12 mmHg. RESULTS: LSM, SSM were significantly higher in patients with HVPG ≥ 10 - < 12 in comparison to HVPG < 10 mmHg (p < 0.001 and p < 0.001, respectively), and in patients with HVPG ≥ 12 mmHg in comparison to ≥ 10 - < 12 mmHg (p < 0.001 and p < 0.001, respectively). LSM and SSM were able to diagnose HVPG ≥ 10 mmHg and HVPG ≥ 12 mmHg with high diagnostic performance (AUC LSM: 0.93 and 0.87, respectively; AUC SSM: 0.97 and 0.95, respectively). The AUC of SSM in predicting esophageal varices (EVs) plus HVPG ≥ 10 mmHg and EVs plus HVPG ≥ 12 mmHg were higher compared to LSM in both groups of patients (SSM: 0.90 and 0.93 vs. LSM: 0.84 and 0.88, respectively). No significant difference between both AUCs was detected in the different HVPG groups. In the multivariate -analysis SSM remained a factor predicting HVPG (HVPG > 10 mmHg p = 0.007; HVPG ≥ 12 mmHg p = 0.003). CONCLUSION: LSM and SSM by ARFI are noninvasive diagnostic tools that may help in diagnosing CSPH. LSM and SSM could be used as a guiding noninvasive screening tool in patients with esophageal varices requiring endoscopic evaluation.

Opposing roles of ERα and ERß in the genesis and progression of adenocarcinoma in the rat ventral prostate.

BACKGROUND: Prostate cancer is a common malignancy in men and although hormone ablation therapy is effective, men develop hormone resistance. There is need for therapies applicable earlier, such as treatment of prostatic intraepithelial neoplasia (PIN). Estrogens besides androgens play a role in prostate cancer pathogenesis via two receptors ERα and ERß and both receptors are thought to play different, opposing, roles with ERα having proliferative properties and ERß having anti-proliferative properties. To differentiate between the roles both receptors play in prostate cancer an ERα and an ERß agonist, ERA-45 and ERB-26, have been tested in a rodent model for prostate carcinogenesis. METHODS: The influence of ERα on prostate cancer progression was studied in intact male rats treated with testosterone in combination with the ERα agonist, ERA-45 for either a long-term (20-week) period or a shorter term (6-week) period. The ERß agonist was tested in the shorter term model in intact male rats treated with testosterone in combination with the ERα agonist, ERA-45, followed by administration of the ERß agonist, ERB-26, during the last 2 weeks. RESULTS: Treatment of rats with testosterone in combination with ERA-45 induced mild PIN lesions at 6 weeks and severe precancerous PIN lesions at 20 weeks. The ERß agonist prevented the onset of PIN lesions at 6 weeks. Moreover, prostate epithelial cell apoptosis was increased and proliferation was decreased. CONCLUSION: These findings confirm the opposing roles ERα and ERß play in prostate carcinogenesis and suggest a therapeutic opportunity of ERß for treating precancerous PIN lesions.

Light-emitting diodes (LED) for domestic lighting: any risks for the eye?

Light-emitting diodes (LEDs) are taking an increasing place in the market of domestic lighting because they produce light with low energy consumption. In the EU, by 2016, no traditional incandescent light sources will be available and LEDs may become the major domestic light sources. Due to specific spectral and energetic characteristics of white LEDs as compared to other domestic light sources, some concerns have been raised regarding their safety for human health and particularly potential harmful risks for the eye. To conduct a health risk assessment on systems using LEDs, the French Agency for Food, Environmental and Occupational Health & Safety (ANSES), a public body reporting to the French Ministers for ecology, for health and for employment, has organized a task group. This group consisted physicists, lighting and metrology specialists, retinal biologist and ophthalmologist who have worked together for a year. Part of this work has comprised the evaluation of group risks of different white LEDs commercialized on the French market, according to the standards and found that some of these lights belonged to the group risk 1 or 2. This paper gives a comprehensive analysis of the potential risks of white LEDs, taking into account pre-clinical knowledge as well as epidemiologic studies and reports the French Agency's recommendations to avoid potential retinal hazards.

Male gender increases sensitivity to proteinuria induced by mild NOS inhibition in rats: role of sex hormones.

Men are at greater risk for renal injury than women. We studied whether male rats are more sensitive to the hypertensive and proteinuric effects of chronic nitric oxide synthase (NOS) inhibition than female rats. In addition, we studied whether androgens or estrogens are responsible for differences in sensitivity to proteinuria induced by chronic NOS inhibition. Females and males were treated with 10, 20, 30, and 100 mg/l N(omega)-nitro-L-arginine (L-NNA) during 24 wk. Systolic blood pressure (SBP) and proteinuria were measured regularly and compared with time-control measurements in control females and males. In females and males treatment with 10 mg/l L-NNA had no effect on SBP or proteinuria. Treatment with 20, 30, and 100 mg/l L-NNA resulted in a dose-dependent increase in SBP that was similar in males and females. However, females treated with 20 and 30 mg/l L-NNA were resistant to the development of proteinuria: maximum values were 16 +/- 7 and 46 +/- 21, respectively, vs. 16 +/- 3 mg/day in controls, whereas males treated with those doses showed an increase in proteinuria [139 +/- 35 (P < 0.05) and 318 +/- 82 (P < 0.01), respectively, vs. 55 +/- 11 mg/day in controls]. Treatment with 100 mg/l L-NNA increased proteinuria similarly in both females and males. To study the role of sex hormones in differences in sensitivity to proteinuria induced by mild chronic NOS inhibition, treatment with 20 mg/l L-NNA was repeated in ovariectomized (Ovx) and orchidectomized rats. Ovariectomy did not affect the increase in SBP caused by 20 mg/l L-NNA, but, in contrast to intact females, this dose of L-NNA did cause Ovx rats to develop proteinuria (51 +/- 16 vs. 16 +/- 7 mg/day in control Ovx rats; P < 0.05). Orchidectomy completely prevented the increased SBP as well as proteinuria induced by 20 mg/l L-NNA in male rats. In conclusion, male rats are more sensitive than female rats to develop proteinuria induced by mild chronic NOS inhibition. Estrogens provide some protection in females, whereas androgens are responsible for the increased sensitivity of male rats to proteinuria induced by mild chronic NOS inhibition. Risk factors associated with a compromised nitric oxide system may be more detrimental to the kidney in men than in women.

Soot-exposed mononuclear cells increase inflammatory cytokine mRNA expression and protein secretion in cocultured bronchial epithelial cells.

BACKGROUND: Soot particles are air pollutants capable of inducing airway and lung parenchymal injury. Mononuclear and bronchial epithelial cells are central to the maintenance of homeostasis and inflammation in the airways. OBJECTIVES: The aim of this study was to evaluate the contribution of mononuclear cells to the release of inflammatory mediators by bronchial epithelial cells. METHODS: To model the in vivo situation, an in vitro system of cocultured blood monocytes and BEAS-2B cells was established in a transwell system. Blood monocytes were exposed to soot particles (FR 101) at concentrations of up to 100 microg/10(6) cells. Inflammatory cytokine mRNA and protein concentrations were quantified in BEAS-2B mono- and BEAS-2B-BM cocultures by RT-PCR and ELISA following exposure to soot for 1 and 8 h. RESULTS: No inflammatory cytokine mRNA expression was observed in unstimulated BEAS-2B cells. IL-6 and IL-8 mRNA and protein levels showed a dose-dependent elevation in FR 101-exposed blood monocytes. In addition, both IL-6 and IL-8 mRNA expression was upregulated in cocultured BEAS-2B cells while cytokine concentrations in the blood monocyte-BEAS-2B coculture medium were significantly increased. This upregulation was likely due to a synergism of two cell populations. CONCLUSIONS: Exposure to soot particles induces an autocrine stimulation of inflammatory cytokine release by blood monocytes and BEAS-2B cells. Since IL-6 and IL-8 play a major role in the pathogenesis and persistence of bronchial inflammation, these findings may serve as a partial explanation for the aggravation of asthmatic and bronchitic symptoms after exposure to soot.