Urinary biomarkers for early detection of platinum based drugs induced nephrotoxicity.

BACKGROUND: Nephrotoxicity is a major hazard complicating the use of platinum based drugs (PBD), which can hinder using higher doses protocols to maximize the therapeutic gain. Shortage of serum creatinine level as an accurate biomarker for acute kidney injuries (AKI) necessitates searching for novel biomarkers with better sensitivity and specificity in patients on PBD. METHODS: In a prospective cohort design, 132 patients receiving PBD were selected for the study. AKI was diagnosed by continuous follow up of serum creatinine level according to Kidney Disease: Improving Global Outcomes (KDIGO) guidelines 2012. Serum creatinine and urinary biomarkers (KIM-1, NGAL and cystatin C) was measured in the day of treatment and for 3 days after PBD cycle. RESULTS: AKI occurred in 35 patients (26.52% of patients). KIM-1, Cystatin C, and NGAL showed significant increase in samples collected in the day of AKI in comparison to their corresponding basal levels (P <  0.0001). In addition, significant increase in urinary levels of the biomarkers in samples collected 1 day before AKI in comparison to their basal levels (P <  0.0001, P <  0.0001, and P = 0.013 for KIM-1, NGAL and Cystatin C respectively). Furthermore KIM-1 data showed a significant increase 2 days before serum creatinine rise in comparison to the corresponding KIM-1 levels in patients who developed AKI (P = 0.001). CONCLUSIONS: Urinary KIM-1, Cystatin C and NGAL can predict PBD induced AKI in earlier stages than serum createnine. KIM-1 is the most sensitive biomarker for early detection of AKI in patients receiving PBD.

The global burden of viral hepatitis from 1990 to 2013: findings from the Global Burden of Disease Study 2013.

BACKGROUND: With recent improvements in vaccines and treatments against viral hepatitis, an improved understanding of the burden of viral hepatitis is needed to inform global intervention strategies. We used data from the Global Burden of Disease (GBD) Study to estimate morbidity and mortality for acute viral hepatitis, and for cirrhosis and liver cancer caused by viral hepatitis, by age, sex, and country from 1990 to 2013. METHODS: We estimated mortality using natural history models for acute hepatitis infections and GBD's cause-of-death ensemble model for cirrhosis and liver cancer. We used meta-regression to estimate total cirrhosis and total liver cancer prevalence, as well as the proportion of cirrhosis and liver cancer attributable to each cause. We then estimated cause-specific prevalence as the product of the total prevalence and the proportion attributable to a specific cause. Disability-adjusted life-years (DALYs) were calculated as the sum of years of life lost (YLLs) and years lived with disability (YLDs). FINDINGS: Between 1990 and 2013, global viral hepatitis deaths increased from 0·89 million (95% uncertainty interval [UI] 0·86-0·94) to 1·45 million (1·38-1·54); YLLs from 31·0 million (29·6-32·6) to 41·6 million (39·1-44·7); YLDs from 0·65 million (0·45-0·89) to 0·87 million (0·61-1·18); and DALYs from 31·7 million (30·2-33·3) to 42·5 million (39·9-45·6). In 2013, viral hepatitis was the seventh (95% UI seventh to eighth) leading cause of death worldwide, compared with tenth (tenth to 12th) in 1990. INTERPRETATION: Viral hepatitis is a leading cause of death and disability worldwide. Unlike most communicable diseases, the absolute burden and relative rank of viral hepatitis increased between 1990 and 2013. The enormous health loss attributable to viral hepatitis, and the availability of effective vaccines and treatments, suggests an important opportunity to improve public health. FUNDING: Bill & Melinda Gates Foundation.

Study of plasmid mediated quinolone resistance genes among Escherichia coli and Klebsiella pneumoniae isolated from pediatric patients with sepsis.

The resistance to antibiotics in Gram-negative bacilli causing sepsis is a warning sign of failure of therapy. Klebsiella pneumoniae (K. pneumoniae) and Escherichia coli (E. coli) represent major Gram-negative bacilli associated with sepsis. Quinolone resistance is an emerging resistance among E. coli and K. pneumoniae. Therefore, the present study aimed to study the presence of plasmid-mediated quinolone resistance (PMQR) genes qnrA, qnrB, and qnrS by polymerase chain reaction (PCR) in E. coli and K. pneumoniae isolated from pediatric patients with sepsis. This was a retrospective cross-sectional study that included pediatric patients with healthcare-associated sepsis. The E. coli and K. pneumoniae isolates were identified by microbiological methods. PMQR genes namely qnrA, qnrB, and qnrS were detected in E. coli and K. pneumoniae isolates by PCR. The results were analyzed by SPPS24, and the qualitative data was analyzed as numbers and percentages and comparison was performed by Chi-square test, P was significant if < 0.05. The most prevalent gene detected by PCR was qnrA (75%), followed by qnrB (28.1%), and qnrS (25%). The most frequently detected qnr gene in E coli and K. pneumoniae was qnrA (28.8%, and 16.3% respectively). The present study highlights the high prevalence of ciprofloxacin resistance among E. coli and K. pneumoniae isolated from pediatric patients with healthcare-associated sepsis. There was a high frequency of PMQR genes in E. coli and K. pneumoniae isolated from pediatric patients. Therefore, it is important to monitor the spread of PMQR genes in clinical isolates to ensure efficient antibiotic use in those children. The finding denotes the importance of an antibiotics surveillance program.

Molecular, Epidemiological and Clinical Assessment of Adenoviral Keratoconjunctivitis in Egypt: Institutional Study.

PURPOSE: To evaluate the frequency of Human adenovirus (HAdV) and its serotypes in keratoconjunctivitis patients who attended the outpatient clinics of Mansoura Ophthalmic Center, Egypt. METHODS: Conjunctival secretions and corneal scrapings were collected from patients complaining of clinically diagnosed viral keratoconjunctivitis. The molecular method for HAdV detection was performed by polymerase chain reaction (PCR) followed by restriction enzymes (REA) determination of serotypes for hexone gene. RESULTS: HAdV infection was detected in 38% of samples. There were 4 serotypes of Human adenovirus species D (HAdV-D) isolated (4, 8, 37, 3), where HAdV-D8 was the most dominant. Contact with infected patient, follicular conjunctivitis and subepithelial corneal infiltrates are useful features for clinical diagnosis of adenoviral conjunctivitis. CONCLUSION: HAdV was significant etiological factor of acute follicular conjunctivitis. Accurate diagnosis of adenoviral conjunctivitis is essential for appropriate management, reducing permanent visual impairment and to limit the transmission of the virus within the community.

Safety and Efficacy of Ledipasvir/Sofosbuvir in the Treatment of Chronic Hepatitis C Virus Infection in Treatment-Naïve Children without and with Comorbidities.

BACKGROUND: Chronic hepatitis C virus (HCV) infection represents a crucial health problem in children that greatly influences their quality of life. Many efforts have been directed toward investing in effective drugs with a high safety profile and oral administration for better compliance. OBJECTIVES: This study aims to assess the safety of a fixed-dose combination of ledipasvir/sofosbuvir plus drug efficacy and sustained virologic response (SVR) at 12 weeks after treatment discontinuation. METHOD: One tablet (90 mg ledipasvir, 400 mg sofosbuvir) was administered to treatment-naïve children aged 12-18 years weighing at least 35 kg with chronic HCV infection for 6 months, genotype 4. Patients were divided into 2 groups, (1) without comorbidities (24 patients) and (2) with comorbidities (26 patients). RESULTS: At the end of the therapy, all patients (100%) had SVR and a significant reduction of liver enzymes with mild tolerable side effects. CONCLUSION: Ledipasvir/sofosbuvir fixed-dose combination is a safe and highly effective therapeutic option in Egyptian children aged ≥ 12 years, with chronic HCV infection, genotype 4, either without or with comorbidities.

Role of hepatitis E infection in acute on chronic liver failure in Egyptian patients.

BACKGROUND: The vast majority of patients who are referred to a specialist hepatological centre suffer from acute deterioration of their chronic liver disease. Yet, this entity of acute on chronic liver failure remains poorly defined. AIM: The aim of the present study was to highlight the occurrence of hepatitis E viraemia by nested reverse transcriptase polymerase chain reaction (RT-PCR) in patients with acute on chronic liver failure. MATERIALS AND METHODS: The study included 100 patients with acute on chronic liver disorders admitted to Mansoura University Hospital, Egypt. Blood samples were obtained from patients and sera were separated. Sera were subjected to a study of viral hepatitis markers for hepatitis A by IgM, for hepatitis B by S antigen and core IgM and for hepatitis C virus by IgG and RT-PCR for HCV. Liver function tests were evaluated including alanine transaminase, aspartate transaminase and bilirubin total and direct by an autoanalyser. Study for hepatitis E virus (HEV) was performed using a molecular technique. Nested RT-PCR was performed for each serum sample. RESULTS: HEV RNA was detected in the sera of 13 patients (13%) of the patients with chronic liver disorders. The majority of the positive cases were among patients with cirrhosis (29.9%) followed by patients with HCC (15.4%). On multirisk analysis for the factors associated with the presence of HEV viraemia, younger age < 45 years and lower albumin level < 3.5 g/dl were significantly (P = 0.04, P = 0.03) associated with HEV viraemia. DISCUSSION: From this study it appears that HEV viraemia is a common cause of acute on chronic liver disorders in Egypt. CONCLUSION: There is no effective vaccine is available against HEV, mass awareness and preventive measures are important to the related.

Evaluation of interleukin-8 in hepatitis C virus infection: relation to combined peg-interferon ribavirin response and genotype 4.

Hepatitis C virus (HCV), a major cause of liver disease worldwide, is frequently resistant to the antiviral alpha interferon (IFN). Previous studies have shown that HCV NS5A protein induces expression of the proinflammatory interleukin-8 (IL-8) and this may affect the therapeutic outcome. The aim of the present study was to investigate the relationship among levels of IL-8 in serum of subjects with past exposure to HCV indicated by positive IgG to HCV and negative PCR, patients with chronic HCV infections and in responder to combined alfa IFN and ribavirin therapy. The study included 48 Egyptian subjects with evidence of HCV infection. They were classified according to viremia to patients with chronic hepatitis C with positive viremia and immune subjects with positive HCV IgG alone. Chronic HCV patients were followed after therapy and 16 healthy adults as control group. It was found that viral load was dependent factor for the level of IL 8 (P = 0.003) and there was significant correlation between levels of IL-8 before treatment and after treatment. The present study highlights the kinetic of serum levels of interleukin-8 in patients with chronic hepatitis C genotype 4 before and after therapy with combined alfa interferon and ribavirin. It was demonstrated that HCV infection was associated with higher levels of interleukin-8 in pretreatment and posttreatment period. Moreover, immune subjects also had higher level of interleukin-8, indicating its role in immunity to HCV infection.

Analysis of Fat Content with Special Emphasis on Trans Isomers in Frequently Consumed Food Products in Egypt: The First Steps in the Trans Fatty Acid Elimination Roadmap.

Trans Fatty Acid (TFA) intake is a risk factor for coronary heart diseases and cancer. Egypt, considered among the highest TFA consumers in the world, lacks proper dietary analysis of TFAs. This cross-sectional study aimed to analyze TFAs in traditional and frequently consumed food products. A market survey was conducted to identify products and brands that are mostly consumed in major governorates in Egypt. Laboratory analysis allowed for the profiling of TFAs, and saturated and unsaturated fatty acids. Products having more than 2 g of TFA/100 g of fat were considered to have an elevated TFA content. Commonly consumed food items (n = 208) in the Egyptian market were identified. On average, 34% of the products exceeded the TFA limit. Sambosk meat, a traditional meat item, had the highest TFA content of 5.2%, followed by foods fried with used oils. Oriental sweets had a TFA content three times higher than that of doughnuts. The fast-food group had the largest proportion of TFA-rich products, followed by the canned and frozen item groups and confectionaries. This study revealed that around one third of products in the Egyptian market have a high TFA content. This calls for urgent legislative action to regulate composition.

MicroRNA-451 as an Early Predictor of Chronic Kidney Disease in Diabetic Nephropathy.

BACKGROUND: Diabetes mellitus is the leading cause of end-stage renal disease worldwide. Microalbuminuria is the cornerstone for the diagnosis of diabetic nephropathy. However, it is an inadequate marker for early diagnosis. MicroRNAs are not only new and promising markers for early diagnosis but also, but they may also play a role in the prevention of disease progression. METHODS: This study included ninety patients with type 2 DM in addition to 30 control subjects. MicroRNA-451 expression in blood and plasma using real-time PCR was evaluated in addition to the classic diabetic nephropathy markers (serum creatinine, urinary albumin, and eGFR). RESULTS: There was a significant difference between the studied groups versus control regarding serum creatinine, eGFR, urinary, and plasma microRNA-451 with p=0.0001. Patients with eGFR 60 ml/min/1.73 m2 showed a significantly higher plasma microRNA-451 (29.6 ± 1.6) and significantly lower urinary microRNA-451 (21 ± 0.9) in comparison to patients with eGFR >60 ml/min/1.73 m2 and p=0.0001. eGFR showed a positive correlation with urinary microRNA-451 and negative correlation with both plasma microRNA-451 and urinary albumin. Both plasma and urinary microRNA-451 are highly sensitive and specific markers for chronicity in diabetic nephropathy patients with sensitivity of 90.9% and 95.5% and specificity of 67.6% and 95.6%, respectively. CONCLUSION: MicroRNA-451 is a promising early biomarker for chronic kidney disease in diabetic nephropathy with high sensitivity and specificity.

Molecular study of human astrovirus in Egyptian children with acute gastroenteritis.

INTRODUCTION: Human astrovirus (HAstV) has been increasingly identified as an important cause of acute gastroenteritis in young children. Limited information is available about the prevalence and genotype distribution of classic HAstV causing acute gastroenteritis in Egyptian children. METHODS: Stool samples were collected from 100 infants and children attending the gastroenterology outpatient clinic in Mansoura University Children Hospital and suffering from acute gastroenteritis during the period extending from January 2018 to January 2019. Samples were tested for HAstV using reverse transcription PCR. Genotyping was performed using type-specific reverse transcription nested PCR. RESULTS: Among 100 children included in this study, the detection rate of HAstV was 11% (11 patients). There was a significant difference regarding age between cases positive and negative for HAstV (p=0.005). There was a higher prevalence of HAstV in children aged one year or younger. Significant association was detected between HAstV positive cases and rural residence (p=0.002), summer season (p=0.025) and fever (p=0.017). The HAstV genotypes detected were HAstV-8 (8/11, 72.7%), HAstV-3 (2/11, 18.2%) and HAstV-2 (1/11, 9.1%). CONCLUSIONS: This study suggests that HAstV is a common pathogen causing gastroenteritis in Egyptian children especially in rural areas. The most frequent HAstV genotype in our study was HAstV-8.

Molecular study of resistance of Staphylococcus aureus to antiseptic quaternary ammonium compounds.

OBJECTIVES: This study determined the prevalence of qac and smr genes in clinical Staphylococcus aureus isolates from hospital-acquired infections and their susceptibility to quaternary ammonium compounds (QACs) and antibiotics, and correlated the presence of antiseptic resistance genes with antibiotic resistance. METHODS: Susceptibility of 150 non-duplicate clinical S. aureus isolates to antimicrobials and benzalkonium chloride (BAC) was determined by disk diffusion and MIC method, respectively. Resistant strains were analysed by multiplex PCR for the presence of qac and smr genes. RESULTS: Reduced susceptibility to BAC was detected in 30% of isolates (MIC cut-off >8mg/L). QAC resistance genes were detected in 13 isolates with reduced BAC susceptibility. The most frequently detected genes were qacA/B (10 isolates; 22.2%), followed by qacJ (10; 22.2%), smr (8; 17.8%), qacG (8; 17.8%) and qacH (3; 6.7%). There was a strong positive correlation between presence of QAC resistance genes and higher BAC MIC associated with qacA/B, qacJ and smr genes. There was a statistically significant prevalence of antiseptic resistance genes among isolates resistant to cefoxitin, ciprofloxacin, clindamycin, oxacillin, tetracycline and erythromycin. CONCLUSION: This study highlights the prevalence of qac and smr genes in clinical S. aureus isolates with resistance to QACs. There was an association between the presence of antiseptic resistance genes and resistance to different antibiotics, which may be attributed to the presence of both groups of genes on the same plasmid or to selection of resistant strains. More studies are needed on the clinical relevance of the presence of genes controlling resistance to antiseptics.

Molecular Study of Parvovirus B19 Infection in Children with Acute Myeloid Leukemia

Background: Parvovirus B19 is a common viral infection in children. Nearby evidences are present about its association with acute leukemia, especially acute lymphoblast leukemia. Nevertheless, scanty reports have discussed any role in acute myeloid leukemia (AML). Purpose: To evaluate the frequency of virological markers of B19 infection including its DNA along with specific immunoglobulins G (IgG) and M (IgM) among children with newly diagnosed AML. Besides, describing the clinical importance of Parvovirus B19 infection in those patients. Patients and methods: A case-control retrospective study was conducted on 48 children recently diagnosed with AML before and during chemotherapy induction and 60 healthy control. Specific serum IgM and IgG levels were determined by enzyme linked immunosorbant assay (ELISA) and DNA detection by polymerase chain reaction (PCR). Results: Parvovirus DNA was detected in 20 patients with AML. IgM was found in sera of four patients and one case had positive DNA and IgG (5%). Patients with recent parvovirus B19 infection had a significantly reduced hemoglobin levels, RBCs counts, platelet counts, neutrophil counts and absolute lymphocytosis (p=0.01, p=0.0001, p=0.01, p=0.02, p=0.0003, respectively). There were no clinical findings with statistically significant association to recent infection. Half of the patients with AML had positive PCR and/or IgM for parvovirus B19. Among children with AML under chemotherapy, there were reduced hemoglobin levels (P=0.03), reduced platelet counts (P=0.0001) and absolute neutropenia (mean±SD, 1.200 ±1.00) in those with parvovirus B19 infection. More than half of patients with parvovirus B19 (72.2%) had positive PCR and/or IgM and 36.4% of them had positive IgG. Conclusion: This study highlights that parvovirus B19 is common in children with AML either at diagnosis or under chemotherapy. There are no clinical manifestations that can be used as markers for its presence, but hematological laboratory findings can provide evidence for infection in the presence of anemia and neutropenia. Detection of parvovirus B19 by combined molecular and serological markers is required in such patients for accurate diagnosis.

Diagnosis of Shiga toxin producing Escherichia coli infection, contribution of genetic amplification technique.

There has been no culture method of choice for detecting non-O157 Shiga toxin-producing Escherichia coli strains (STEC) because of their biochemical diversity The aim of this study was the assessment of verotoxin gene detection (VT1/VT2) within STEC PCR compared with the Vero cells cytotoxicity among O157 and non-O157 STEC serotypes. Stool cultures were performed on Tryptic Soy Broth and sorbitol MacConkey agar with cefixitime and tellurite supplements which were identified as Escherichia coli (E. coli) by BBL crystal. Further identifications were performed including verotoxin production assessment by Vero cells cytotoxicity assay, PCR for specific VT1/VT2 genotyping, and isolates were plated on blood agar and tested for enterohemolysis. Vero cells cytotoxicity assay revealed that 58 of E. coli isolates (71.6%) were STEC. In PCR, 33 (56.9%) of the 58 strains were positive for the VT2 gene, 24 (41.4%) were positive for the VT1 gene and one isolate was positive for both genes. In comparison to Vero cells cytotoxicity, the sensitivity, specificity of PCR were 100%. In comparative study between verotoxin assessment by Vero cells cytotoxicity and enterohemolytic activity, concordance positive results between both were 53 (91.4%). The most common serogroups of STEC were O157 (33%) and O26 (20%). From this study we can conclude that enterohemolysin production can be used as surrogate marker for STEC. The most rapid and promising approach for detection of STEC is by molecular method.

Rapid phenotypic assay of antimycobacterial susceptibility pattern by direct mycobacteria growth indicator tube and phage amplified biological assay compared to BACTEC 460 TB.

The performance of antimycobacterial susceptibility testing for the first line drugs (isoniazid, streptomycine, rifampicin and ethambutol) with mycobacteria growth indicator tube (MGIT) and by bacteriophage amplified biological assay by FAST-plaque TB-MDR were compared to automated radiometric BACTEC 460 TB system. This study was carried on 84 sputum samples of positive Zhiel-Neelsen (ZN) smears. Sputum samples were subjected to culture and antimycobacterial susceptibility testing by BACTEC 460 TB. Samples were also tested by direct susceptibility tests for isoniazid (INH), ethambutol, rifampicin (RIF) and streptomycine by MGIT. Sensitive and resistant isolates for RIF were further studied by FAST-plaque TB-MDR for RIF resistance. The commonest resistance pattern by BACTEC 460 TB was for INH (32%) followed by RIF (24%) either alone or in combination with other drugs. Multiple drugs resistance was 20%. The agreement between BACTEC 460 TB and direct MGIT for resistant strains was 100% for INH and ethambutol, 91.7% for rifampicin, 80% for streptomycine and was 90% for MDR. FAST-plaque TB-MDR detected correctly all RIF resistant strains and 97.2% of the sensitive strains. For majority of strains direct susceptibility tests were available within 6.34-6.404 days (95% confidence interval) with direct mycobacteria growth tube, while results for FAST-plaque TB-MDR appear within 10.5-11.5 days from the time that the sputum was received in the laboratory (95% confidence interval). From this study, we could conclude that direct MGIT AST is the quickest method for screening antimycobacterial susceptibility pattern for the drugs commonly used (INH, RIF, etambutol, streptomycin) as results were available within 6.34-6.404 days. Also FAST-plaque TB-MDR method is accurate for detection of rifampicin resistance after primary culture which can be used as a surrogate marker for presence of MDR strains and the results were available within 10.5-11.5 days.

Molecular Study of Acinetobacter baumannii Isolates for Metallo-ß-Lactamases and Extended-Spectrum-ß-Lactamases Genes in Intensive Care Unit, Mansoura University Hospital, Egypt.

Acinetobacter baumannii (A. baumannii) has been known as a causative pathogen of hospital acquired infections. The aim of this study is to examine the presence of A. baumannii among clinical isolates from intensive care unit (ICU) in Mansoura University Hospital (MUH), its antibiotic resistance pattern, and prevalence of antibiotic resistance genes metallo-ß-lactamases (MBLs) and extended-spectrum-ß-lactamases (ESBLs) among A. baumannii isolates. A. baumannii was identified by colony morphology, API 20E, and confirmed by detecting the bla OXA-51-like carbapenemase gene by PCR. Phenotypic expression of MBLs resistance was demonstrated by Combined Disk Test (CDT) in 273 isolates (97.5%) and of ESBLs was demonstrated by double disc synergy method (DDST) in 6 isolates (2.1%). MBLs genes were positive in 266 isolates (95%) and ESBLs genes were positive in 8 isolates (2.9%). The most frequent genes of MBLs studied genes were IMP (95.7%) followed by SIM and GIM (47.1% and 42.9%; resp.). For ESBL genes, the most frequent gene was TEM (2.9%). From this study, we conclude that multidrug resistant (MDR) A. baumannii with MBLs activity was the most common isolate. Careful monitoring for the presence of MDR A. baumannii among hospitalized patients is recommended to avoid wide dissemination of antibiotic resistance.

Value of procalcitonin as a biomarker for postoperative hospital-acquired pneumonia after abdominal surgery.

BACKGROUND: Hospital-acquired pneumonia (HAP) is a common complication after abdominal surgery. The aim of this study was to evaluate the role of procalcitonin (PCT) and C-reactive protein (CRP) as early biomarkers for the diagnosis of postoperative HAP after abdominal surgery. METHODS: This study was conducted on 100 patients undergoing abdominal surgery. White blood cell counts, highest body temperature, and serum levels of CRP and PCT were recorded preoperatively and daily postoperatively until postoperative day (POD) 5. Chest radiography was performed preoperatively and daily postoperatively until POD 5. RESULTS: HAP was diagnosed in 14% of patients. Regarding the biomarkers studied after POD 1, CRP and PCT were significantly higher in patients with HAP than in those without HAP (P < 0.05). On POD 2, PCT had higher sensitivity and specificity (84% and 72%, respectively) than those for CPR (70% and 60%, respectively). The cut-off value of PCT on POD 2 was 1.4 ng/ml. On POD 3, 4, and 5, the sensitivity and specificity of PCT and CRP were not significantly different. CONCLUSIONS: PCT and CRP are accurate biomarkers for early prediction of postoperative HAP after abdominal surgery. The diagnostic ability of PCT was significantly better than that of CRP on POD 2. After POD 2, the diagnostic ability was not significantly different between the biomarkers.

Genetic Polymorphisms of Fas/FasL Promoter Associated with Hepatitis C cirrhosis and HCC

Aim: The present study was performed to determine any associations of genetic polymorphisms of Fas/FasL promoter regions, at Fas670 and Fas1377 and FasL844, with hepatitis C cirrhosis and HCC, with a focus on severity of disease. Methods: Totals of 120 patients with cirrhosis and 101 with hepatocellular carcinoma (HCC) were enrolled. All had chronic HCV infection as indicated by positive anti-HCV antibodies and positive HCV RNA on real time PCR. One hundred healthy control subjects were also included in the study. Patients were subjected to full clinical, radiological and histopathological examinations. In addition to routine laboratory tests for liver function tests, Fas670 and Fas1377 and FasL844 genetic polymorphisms of Fas/FasL promoter regions were assessed by RFLP-PCR (restriction fragment length polymorphism with polymerase chain reaction). Results: Significant higher levels of the AG genotype in Fas670 and Fas1773 were observed in patients with cirrhosis and HCC (P=0.0001) as compared to control subjects. In addition, the CC genotype in FASL844 was also more common in patients (P=0.01). Furtehrmore, there was a significant association of substitution of A by G alleles in Fas670 and Fas1773 with advanced BCA staging (P=0.02, P=0.0001 respectively) and larger tumor size >5cm (P=0.01, P=0.0001 respectively) and in Fas670 with advanced pathological grading (P=0.0001). Moreover the CC genotype of FASL844 was significantly linked with advanced BCA, large tumor size >5cm and advanced pathological grading (P=0.0001). Conclusion: The findings of the present study highlight associations of genetic polymorphisms of promoter regions in Fas and Fas L with cirrhosis and HCC associated with chronic HCV. Support was also obtained for the conclusion that single nucleotide polymorphisms of the Fas/ FasL system impact on clinical and histopathological grading of HCCs. Further large scale studies are recommended for confirmation.

Global, Regional, and National Burden of Cardiovascular Diseases for 10 Causes, 1990 to 2015.

BACKGROUND: The burden of cardiovascular diseases (CVDs) remains unclear in many regions of the world. OBJECTIVES: The GBD (Global Burden of Disease) 2015 study integrated data on disease incidence, prevalence, and mortality to produce consistent, up-to-date estimates for cardiovascular burden. METHODS: CVD mortality was estimated from vital registration and verbal autopsy data. CVD prevalence was estimated using modeling software and data from health surveys, prospective cohorts, health system administrative data, and registries. Years lived with disability (YLD) were estimated by multiplying prevalence by disability weights. Years of life lost (YLL) were estimated by multiplying age-specific CVD deaths by a reference life expectancy. A sociodemographic index (SDI) was created for each location based on income per capita, educational attainment, and fertility. RESULTS: In 2015, there were an estimated 422.7 million cases of CVD (95% uncertainty interval: 415.53 to 427.87 million cases) and 17.92 million CVD deaths (95% uncertainty interval: 17.59 to 18.28 million CVD deaths). Declines in the age-standardized CVD death rate occurred between 1990 and 2015 in all high-income and some middle-income countries. Ischemic heart disease was the leading cause of CVD health lost globally, as well as in each world region, followed by stroke. As SDI increased beyond 0.25, the highest CVD mortality shifted from women to men. CVD mortality decreased sharply for both sexes in countries with an SDI >0.75. CONCLUSIONS: CVDs remain a major cause of health loss for all regions of the world. Sociodemographic change over the past 25 years has been associated with dramatic declines in CVD in regions with very high SDI, but only a gradual decrease or no change in most regions. Future updates of the GBD study can be used to guide policymakers who are focused on reducing the overall burden of noncommunicable disease and achieving specific global health targets for CVD.

Acute sporadic hepatitis E in children: diagnostic relevance of specific immunoglobulin M and immunoglobulin G compared with nested reverse transcriptase PCR.

This study was carried out to investigate the putative role played by the hepatitis E virus (HEV) in acute hepatic dysfunction in paediatric patients with acute non-A-C hepatitis. We also evaluated the diagnostic value for anti-HEV immunoglobulin G (IgG) and IgM enzyme-linked immunosorbent assays relative to nested reverse transcriptase PCR (RT-PCR) for HEV RNA detection. Sixty-four children with acute hepatitis were included in the study, in addition to sixteen healthy children with matched age and sex. All studied subjects were negative for IgM antibody to hepatitis A virus, hepatitis B virus surface antigen, IgM antibody to hepatitis B virus core antigen, antibody to hepatitis C virus, and by RT-PCR for HCV RNA. HEV RNA was detected in 23.4% of patients, followed by detection of specific IgM in 17.2% and IgG in 12.5% of patients. Two cases were positive for IgG in the control group (12.5%). The sensitivity, specificity and accuracy were 26.7%, 85.7%, 71.9%, respectively, for IgM, and 26.7%, 91.8%, and 76.6%, respectively, for IgG. From this study we can conclude that HEV is a frequent virus found sporadically with acute hepatitis among paediatric patients. We cannot depend upon serology alone for diagnosis; rather, both molecular and serological methods must be applied for accurate diagnosis.

Maternal-Fetal Hepatitis E Transmission: Is It Underestimated?

Hepatitis E virus (HEV) is an enterically transmitted virus; and several modes of transmission have been proposed, including blood transfusion, person to person transmission, and transplacental transmission. HEV during pregnancy is associated with an unfavorable prognosis for mothers and in severe cases can cause acute fulminate hepatitis and death. Transplacental transmission of HEV usually results in unfavorable outcomes of pregnancy, mainly fetal loss, preterm labor, and hepatic dysfunction in neonates. In this review, we will summarize the effects of HEV on maternal-fetal health in various clinical situations.