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- Long-Term Safety and Efficacy of Atazanavir-Based Therapy in HIV-Infected Infants, Children and Adolescents: The Pediatric AIDS Clinical Trials Group Protocol 1020A. [JOURNAL ARTICLE]
- Pediatr Infect Dis J 2014 Sep 17.
Atazanavir is an attractive option for the treatment of Pediatric HIV infection, based on once daily dosing and the availability of a formulation appropriate for younger children. PACTG 1020A was a phase I/II open label study of atazanavir (ATV) (with/without ritonavir [RTV] boosting)-based treatment of HIV-infected children; here we report the long-term safety and virologic and immunologic responses.Antiretroviral-naïve and experienced children, ages 91 days to 21 years, with baseline plasma HIV RNA >5000 copies/ml (cpm) were enrolled at sites in the United States and South Africa.Of 195 children enrolled 142 (73%) subjects received ATV-based regimens at the final protocol recommended dose. 58% were treatment naive. Overall, at week 24, 84/139 subjects (60.4%) and at week 48, 83/142 (58.5%), had HIV RNA ≤400 cpm. At week 48, 69.5% of naïve and 43.3% of experienced subjects had HIV RNA ≤400 cpm; median CD4 increase was 196.5 cells/mm3. The primary adverse event was increased serum bilirubin; 9% of subjects had levels ≥ 5.1 times upper limit of normal and 1.4% noted jaundice. 3% of subjects experienced Grade 2 or 3 prolongation in PR or QTc intervals. At week 48, there was a 15% increase in total cholesterol (TC), with TC >199 mg/dL increasing from 1% at baseline to 5.7%.Use of once-daily ATV, with/without RTV, was safe and well tolerated in children, with acceptable levels of viral suppression and CD4 count increase. The primary adverse event, as expected, was an increase in bilirubin levels.
- Preoperative Serum Bilirubin and Lactate Levels Predict Postoperative Morbidity and Mortality in Liver Surgery: A Single-Center Evaluation. [JOURNAL ARTICLE]
- Scand J Surg 2014 Sep 17.
In spite of huge developments in liver surgery during the last decades, morbidity and mortality continue to pose problems in this field. The aim of this study was to identify preoperative predictors for postoperative mortality and morbidity in liver surgery.In a single-center study, an extensive analysis of a prospective database, including clinical criteria and laboratory tests of patients undergoing liver surgery between July 2007 and July 2012 was performed. Cutoff values of selected laboratory tests were calculated.In all, 337 patients were included in the study. Univariate analysis showed a statistically significant association of preoperative bilirubin, lactate, hemoglobin levels, platelet count, and prothrombin time with postoperative morbidity and mortality. Multivariate analysis revealed preoperatively elevated serum bilirubin and lactate levels as independent predictors for increased postoperative morbidity and mortality after liver surgery.The identified laboratory values showed a statistically significant association with postoperative morbidity and mortality in liver surgery and might be helpful in preoperative patient selection.
- Coexistence of congenital syphilis and cytomegalovirus infection: a case report. [Journal Article]
- Acta Dermatovenerol Croat 2014 Sep; 22(3):215-7.
A 22-year-old pregnant woman with an intravenous drug abuse habit delivered a girl in the 26th gestational week with a fetal length and weight of 38 cm/990 g (pc. 75-91). She did not participate in prenatal care that included screening for congenital diseases, syphilis, and human immunodeficiency virus (HIV) infection during the pregnancy. Laboratory examinations revealed positive rapid plasma reagin (RPR) (1:128), Treponema pallidum particle agglutination assay (TPPA) and TpELISA results. Immediately before delivery, labial herpes simplex virus-1 (HSV-1), Streptococcus agalactiae, and genital yeast infections were detected. Hepatitis B surface antigen (HbsAG), HIV, and hepatitis C virus (HCV) serology remained negative. The preterm and immature newborn girl had mild jaundice, minimal edema, and gluteal hematomas with petechiae. The liver and spleen were extremely enlarged (reaching the plevic bones). Increased muscle tone and rigid elbow, knee, and hip joints were found (Figures 1, 2). Additionally, X-ray examination detected multiple jejunal atresia. Brainstem evoked response audiometry ruled out hearing loss. In laboratory investigations anisocytosis, thrombocytopenia, elevated liver enzymes (ASAT: 3850 U/L, ALAT: 558 U/L, GGT: 292 U/L, ALP: 436 U/L), elevated lactate dehydrogenase (LDH) (38180 mmol/L), and creatinine kinase (CK) (7.1 U/L) with elevated bilirubin levels (87.9 μmol/L) were found. In microbiology investigations a high CMV virus number was detected using a quantitative real-time polymerase chain reaction (PCR) method from the urine and blood. Syphilis serology was positive (RPR: 1:16 positive, TPPA, TpELISA, and T. pallidum IgM immunoblot positive). HSV PCR (in the oral mucosa, conjunctiva, and blood) remained negative. Intravenous penicillin-G (100.000 IU/kg/dose for 10 days) therapy was administered. Intravenous ganciclovir was started, but was discontinued after 2 weeks because of progressive thrombocytopenia and elevating liver enzymes. The newborn underwent transfusion due to anemia and extreme thrombocytopenia. Blue light therapy was administered for 3 days because of jaundice. The multiple jejunal atresia was treated by operation (terminoterminal jejuno-jejunostomia and ileal stricturaplastica) in the Semmelweis University Pediatrics Clinic. At the time of writing this report, the girl was 2 months old, growing and developing; her intestinal passage is satisfactory, but the liver enzymes are extremely high due to the CMV infection. Congenital syphilis and congenital CMV are preventable diseases, but they are still the most common causes of perinatal mortality and morbidity worldwide (4,5). Intravenous drug users and mothers of low socioeconomic status belong to the highest risk groups for vertical transmission of infections. Congenital syphilis may induce jaundice, hepatosplenomegaly, wrinkled skin, thrombocytopenia, and anemia, with symptoms that are clinically similar to congenital CMV infection, making the differential diagnosis difficult (1,5,6). Although syphilis screening tests are mandatory in the first trimester of pregnancy in Hungary, at least one congenital syphilis case was observed yearly since the mid-nineties. Therefore, a second syphilis test is strongly recommended after the 28th gestational week or before delivery, particularly in high risk groups (7). The prenatal diagnosis of fetal CMV infection is based on amniocentesis in the 21st gestational week, which is a risky and non-standard method. The widely used ultrasonography examination often yields a uncertain diagnosis (8). Intravenous penicilline-G is effective treatment for congenital syphilis, but there is no gold standard therapy for CMV infection. Treatment with ganciclovir may prevent hearing loss later in life, but it has several severe side effects (neutropenia, anemia, thrombocytopenia, elevated liver enzymes) (9). Furthermore, studies on the effect of prolonged valganciclovir therapy are still ongoing (10). Prevention is the most effective method of reducing the prevalence of congenital CMV: pregnant women should avoid contact with the saliva of young children. In our case, the mother of the newborn belonged to a high risk group and did not participate in the prenatal caring system; mandatory screening tests were not done, so congenital infections were diagnosed only at delivery. The treatment for congenital syphilis was effective, and resulted in decrease of RPR titers. Most of the clinical symptoms did not improve, and the liver enzymes were continuously increased, indicating that CMV infection was a major contributor in clinical manifestation. Further follow up is needed to evaluate the radiological findings of long bones. Our case draws attention to the importance of early and effective prenatal diagnosis, adequate treatment of prenatal infectious diseases, and the necessity of a multidisciplinary approach to congenital infections.
- Neonatal hyperbilirubinemia and childhood allergic diseases: a systematic review. [JOURNAL ARTICLE]
- Pediatr Allergy Immunol 2014 Sep 17.
Studies have found a link between neonatal hyperbilirubinemia (NNH) and/or phototherapy (NPT) and childhood allergic diseases. The present systematic review was conducted to provide updated evidence, and to provide direction regarding future research.A systematic search of the published literature was done. Observational studies including children up to 12 years of age were included. Data extraction was done using a standardized data extraction form that was designed and pilot tested a priori. The analysis was carried out with the statistical software RevMan (version 5.2) [Protocol is registered at PROSPERO: CRD42014009943].Of 79 citations retrieved, a total of 7 good quality studies (n=101,499) were included in the final analysis. There was a significant increase in the odds of asthma and allergic rhinitis (AR) after NNH [asthma, OR 4.26 (95% CI 4.04-4.5); AR, OR 5.37 (95% CI 4.16-6.92)] and after NPT [asthma, OR 3.81 (95% CI 3.53-4.11); AR, OR 3.04(95% CI 2.13-4.32)]. A similar increase in the trend was noted for late onset asthma after NNH [OR 4.1 (95% CI 2.82-5.94)], and hospitalization due to asthma after NPT [OR 3.56 (95% CI 2.93-4.33)]. The GRADE evidence generated was of "low-quality".The current evidence finds a significant increase in the odds of childhood allergic diseases after NNH and/or NPT. As observational studies were included, the evidence generated was of 'low-quality'. Future studies should try to elucidate the pathophysiologic link between NNH and/or NPT and childhood allergic diseases. This article is protected by copyright. All rights reserved.
- Protective effect of seed oil of Herpetospermum pedunculosum against carbon tetrachloride-induced liver injury in rats. [Journal Article]
- Saudi Med J 2014 Sep; 35(9):981-7.
To investigate the protective effect of Herpetospermum pedunculosum (H. pedunculosum) seed oil against carbon tetrachloride (CCl4)-induced liver damage.This experimental study was conducted at the Northwest Institute of Plateau Biology, Chinese Academy of Sciences, and Yantai University, China from November 2012 to May 2013. The H. pedunculosum seed oil was extracted using supercritical carbon dioxide. The antioxidant activities of H. pedunculosum seed oil were assayed in vitro by 2,2-diphenyl-1-picrylhydrazyl assay, lipid peroxidation assay, and antihemolytic assay. Adult Sprague Dawley rats were randomly divided into 6 groups (10 rats/group) including control, CCl4, CCl4+bifendate, and CCl4+H. pedunculosum seed oil (3 different doses) groups.The CCl4-induced liver lesions include hepatocyte necrosis, ballooning degeneration, calcification, and fibrosis. Moreover, CCl4 damage results in an obvious increase of serum triglycerides, high-density lipoprotein, low-density lipoprotein, malondialdehyde, total bilirubin, alanine aminotransferase, aspartate aminotransferase and alkaline phosphatase activity. In addition, CCl4 also significantly decreased the activities of superoxide dismutase (SOD). By contrast, H. pedunculosum seed oil administration significantly ameliorated the CCl4-induced liver lesions, lowered the serum levels of hepatic enzyme markers, and increased the activities of SOD.The results of this study show that H. pedunculosum seed oil can be proposed to protect the liver against CCl4-induced oxidative damage in rats, and the hepatoprotective effect might be correlated with its potent antioxidant and free radical scavenging effect.
- Effects of propofol versus isoflurane on liver function after open thoracotomy. [JOURNAL ARTICLE]
- Asian Cardiovasc Thorac Ann 2014 Sep 15.
Anesthetic agents and type of surgery may contribute to postoperative hepatic injury. Inhalational anesthetics have been associated with hepatic dysfunction after surgery, however, propofol is expected to have a lower potential for postoperative liver injury. This prospective double-blind randomized clinical study was planned to determine whether postoperative liver function differs after anesthesia with isoflurane and total intravenous anesthesia with propofol in patients undergoing a posterolateral thoracotomy.Eighty-eight patients in American Society of Anesthesiologists physical status 1 or 2, aged 16-60 years, and scheduled for an elective posterolateral thoracotomy, were randomly assigned to an anesthetic protocol: propofol (n = 44) or isoflurane (n = 44). Induction of anesthesia was similar in both groups. Serum levels of aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase, lactate dehydrogenase, total bilirubin, and γ-glutamyltransferase were measured before induction of anesthesia and on the first and third days after either propofol or isoflurane anesthesia.Mild changes in postoperative serum levels of liver enzymes were significant within each group but the differences between groups were not significant.Propofol and isoflurane anesthesia have a comparable minor effect on liver function after an elective posterolateral thoracotomy.
- Combined use of non-biological artificial liver treatments for patients with acute liver failure complicated by multiple organ dysfunction syndrome. [Journal Article]
- World J Emerg Med 2014; 5(3):214-7.
Acute liver failure (ALF) caused by viral and non-viral hepatitis is often accompanied with severe metabolic disorders, the accumulation of toxic substances and continuous release and accumulation of a large number of endogenous toxins and inflammatory mediators. The present study aimed to investigate the effects of various combined non-biological artificial liver treatments for patients with acute liver failure (ALF) complicated by multiple organ dysfunction syndrome (MODS).Thirty-one patients with mid- or late-stage liver failure complicated by MODS (score 4) were randomly divided into three treatment groups: plasmapheresis (PE) combined with hemoperfusion (HP) and continuous venovenous hemodiafiltration (CVVHDF), PE+CVVHDF, and HP+CVVHDF, respectively. Heart rate (HR) before and after treatment, mean arterial pressure (MAP), respiratory index (PaO2/FiO2), hepatic function, platelet count, and blood coagulation were determined.Significant improvement was observed in HR, MAP, PaO2/FiO2, total bilirubin (TBIL) and alanine aminotransferase (ALT) levels after treatment (P<0.05). TBIL and ALT decreased more significantly after treatment in the PE+CVVHDF and PE+HP+CVVHDF groups (P<0.01). Prothrombin time (PT) and albumin were significantly improved only in the PE+CVVHDF and PE+HP+CVVHDF groups (P<0.05). TBIL decreased more significantly in the PE+HP+CVVHDF group than in the HP+CVVHDF and PE+CVVHDF groups (P<0.05). The survival rate of the patients was 58.1% (18/31), viral survival rate 36.4% (4/11), and non-viral survival rate 70% (14/20).Liver function was relatively improved after treatment, but PE+HP+CVVHDF was more efficient for the removal of toxic metabolites, especially bilirubin. The survival rate was significantly higher in the patients with non-viral liver failure than in those with viral liver failure.
- Evaluation of risk factors for development of severe hyperbilirubinemia in term and near term infants in Turkey. [Journal Article]
- Pak J Med Sci 2014 Sep; 30(5):1113-8.
To determine clinical features, etiology and risk factors in term and near term newborns with severe hyperbilirubinemia.During ten years period (2000 - 2009), infants of ≥ 35 gestational weeks who received phototherapy were evaluated retrospectively. The study population was divided into two groups and clinical features, etiology and risk factors were compared. Group 1 defined by those who had bilirubin level ≥25 mg/dl (severe hyperbilirubinemia) and group 2 defined by bilirubin level <25 mg/dl.During the study period 1335 babies were evaluated. Severe hyperbilirubinemia was found in 137 (10.3%) patients. Total serum bilirubin level was 29.7±4.7 mg/dl in group 1 and 18.9±3.5 mg/dl in group 2. Pathological weight loss, vaginal delivery and supplementary feeding were identified as significant risk factors for development of severe hyperbilirubinemia (p <0.001, p <0.001 and p = 0.04, respectively). The time at recognition of jaundice by family and postnatal age at admission were significantly higher in group 1. The ratios of previous sibling received phototherapy and being the second child or after were found higher in group 1.Pathological weight loss, vaginal delivery and supplementary feeding were determined as risk factors for development of severe hyperbilirubinemia. The newborns with severe hyperbilirubinemia had late recognition of jaundice and admission to hospital by their families.
- YKL-40 and Alcoholic Liver and Pancreas Damage and Disease in 86 258 Individuals from the General Population: Cohort and Mendelian Randomization Studies. [JOURNAL ARTICLE]
- Clin Chem 2014 Sep 15.
We tested the hypothesis that observationally and genetically increased YKL-40 concentrations are associated with alcoholic liver and pancreas damage and disease.We performed cohort and Mendelian randomization in 86 258 individuals from the Danish general population, with measured concentrations of plasma YKL-40 (n = 21 646) and CHI3L1 rs4950928 genotype (n = 84 738).Increased YKL-40 was associated with increased alanine aminotransferase, bilirubin, alkaline phosphatase, γ-glutamyl transferase, erythrocyte mean corpuscular volume, C-reactive protein, and fibrinogen and with decreased albumin; coagulation factors II, VII, and X; and pancreatic amylase. The multifactorially adjusted hazard ratio for alcoholic liver cirrhosis comparing the 96%-100% vs 0%-33% YKL-40 percentile categories was 41 (95% CI 14-118). Corresponding ratios were 7.9 (5.1-12) for any alcoholic liver disease, 4.1 (1.7-10) for alcoholic pancreatitis, and 3.4 (1.9-6.1) for any pancreatitis. CHI3L1 rs4950928 genotype explained 14% of the variation in plasma YKL-40 concentrations but was not associated with alcoholic liver and pancreas damage or disease. A doubling in YKL-40 concentrations was associated with a multifactorially adjusted observational hazard ratio of 2.8 (2.4-3.3) for alcoholic liver cirrhosis and a corresponding genetic odds ratio of 1.1 (0.7-1.5). Corresponding risk estimates were 2.0 (1.8-2.2) observationally and 1.0 (0.8-1.1) genetically for any alcoholic liver disease, 1.4 (1.1-1.9) observationally and 1.1 (0.8-1.5) genetically for alcoholic pancreatitis, and 1.3 (1.1-1.6) observationally and 1.0 (0.8-1.3) genetically for any pancreatitis. Excessive alcohol consumption combined with YKL-40 concentrations in the top 5% was associated with 10-year risk of alcoholic liver cirrhosis of up to 7% in ever-smokers and 2% in never-smokers.YKL-40 concentration within the top 5% was a marker for alcoholic liver cirrhosis, with no evidence to support a causal relationship.
- Latex-Enhanced Turbidimetric Immunoassay for Everolimus in Whole Blood Using the Nanopia TDM Everolimus Assay With the JCA-BM6010 Automatic Analyzer. [JOURNAL ARTICLE]
- Ther Drug Monit 2014 Oct; 36(5):677-680.
Everolimus is a novel proliferation signal inhibitor used in immunosuppressive therapies for the prevention of acute and chronic rejection. It is an immunosuppressant requiring routine monitoring in whole blood. We evaluated analytical performance of the Nanopia TDM Everolimus assay kit for the measurement of everolimus in whole blood.Whole blood samples from patients receiving immunosuppressive therapy with everolimus after heart transplantation were used, and everolimus concentrations were measured by liquid chromatography combined with mass spectrometric detection and fluorescence polarization immunoassay and Nanopia TDM Everolimus assay.The within-assay coefficient of variation was 4.0%-6.8% (n = 20) at everolimus concentrations of 4.4-15.7 ng/mL, whereas the day-to-day coefficient of variation ranged from 3.6% to 5.4% at everolimus concentrations of 4.8-15.9 ng/mL. The limit of quantitation was 1.5 ng/mL. Calibration curves were stable for at least 14 days. The presence of conjugated bilirubin, unconjugated bilirubin, lipemic material, rheumatoid factor, and variation of the hematocrit did not affect this assay system. There was a strong positive correlation between values obtained with the Nanopia TDM Everolimus assay kit and the results of liquid chromatography combined with mass spectrometric detection (y = 0.960x + 0.312 ng/mL; r = 0.946; n = 91), as well as with data from the fluorescence polarization immunoassay (y = 0.966x - 0.440 ng/mL; r = 0.942; n = 91).The Nanopia TDM Everolimus assay showed good analytical performance. These results indicate that the Nanopia TDM Everolimus assay may be suitable for routine clinical use.