Detectable Serum Research Articles

The correlations between hepatitis B virus infection and hepatocellular carcinoma with portal vein tumor thrombus or extrahepatic metastasis.

Portal vein tumor thrombus (PVTT) and extrahepatic metastasis are associated with the prognosis of hepatocellular carcinoma (HCC). We aimed to investigate the effect of hepatitis B virus (HBV) infection on HCC patients with PVTT or extrahepatic metastasis. The clinical data of 639 patients with HCC from our hospital were retrospectively analyzed to analyze the correlation between HBV and HCC with PVTT or extrahepatic metastasis. Univariate analysis revealed that positive hepatitis B virus surface antigen (HBsAg), a detectable serum hepatitis B virus DNA load (>500 IU/ml), cirrhosis and ascites were associated with the presence of PVTT. Positive hepatitis B virus e antigen (HBeAg), cirrhosis and ascites were associated with the presence of extrahepatic metastasis. In a multivariate regression analysis carried out a detectable serum hepatitis B virus DNA load, cirrhosis and ascites were independent risk factors of PVTT. Ascites was an independent risk factor of extrahepatic metastasis. The patients in the PVTT of type III/IV group and the PVTT of type I/II group had a significantly higher rate of positive serum HBsAg, a detectable serum hepatitis B virus DNA load (>500 IU/ml) and HBsAg + HBeAb + HBcAb test positive compared with those in the PVTT-negative group. HBsAg + HBeAb + HBcAb test positive was significantly associated with the presence of extrahepatic metastasis (P=0.028). HBV infection and replication status are associated with the formation of PVTT or extrahepatic metastasis in patients with HCC.

Hydrogen-rich saline protects intestinal epithelial tight junction barrier in rats with intestinal ischemia–reperfusion injury by inhibiting endoplasmic reticulum stress-induced apoptosis pathway

AimTo investigate the effects of hydrogen-rich saline (HRS) on intestinal epithelial tight junction (TJ) barrier in rats with intestinal ischemia–reperfusion injury (IIRI). Materials and methodsThirty-two healthy male Sprague–Dawley (SD) rats were randomly divided into four groups (n = 8 each): Sham group, I/R group, HRS group and 4-PBA group. After 45 min of ischemia and 6 h of reperfusion, the rats were sacrificed to collect serum and ileum for detection. Hematoxylin and eosin (H&E) staining was used to observe the morphology of small intestine. The serum expression levels of intestinal fatty acid binding protein (IFABP), tumor necrosis factor-α (TNF-α), and interleukin-1β (IL-1β) were determined by enzyme linked immunosorbent assay (ELISA). Imunohistochemistry, immunofluorescence and Western blot were used to detect key proteins in intestinal epithelial TJs, ERS, and ERS-induced apoptosis, including occludin, zonula occludens-1 (ZO-1), glucose-regulated protein 78 (GRP78), X-box binding protein-1 (XBP1), C/EBP-homologous protein (CHOP) and caspase-3. Data was presented as mean ± SEM and compared using one-way ANOVA. A p-value <0.05 was considered significant. ResultsCompared with rats in the I/R group, the Chiu score of ileum damage in the HRS group and 4-PBA group were lower. The levels of serum IFABP, TNF-α, and IL-1β were statistically significant among the groups. Increased expression of TJ proteins occludin and ZO-1 by reducing various parameters of ERS and ERS-induced apoptosis evidenced by down-regulation of the protein levels of GRP78, XBP1, CHOP and caspase-3 were shown in the HRS and 4-PBA groups. ConclusionHRS had potential protective effects on intestinal barrier in IIRI rats. This study suggested that inhibition of excessive ERS and ERS-induced apoptosis by HRS may reduce intestinal epithelial cells damage and maintain the integrity of intestinal epithelial TJ barrier in rats with IIRI.

Серологічна діагностика вірусу шарки сливи в Україні

Plum pox virus is causative agent of stone fruit trees disease and is a quarantine agent worldwide. The virus is widespread in different regions of Ukraine, posesses a serious threat to the garden industry and the distrubution of the pathogen grows every year. The purpose of our work was to monitor stone fruit cultures for the presence of plum virus in Ukraine, using serological diagnostic methods to determine the prevalence of plum pox virus and further study the molecular and epidemiological features of the pathogen, and to obtain specific diagnostic serum. Firstly, a specific diagnostic serum for detection all strains of plum pox virus was obtained for early and large-scale diagnosis of stone fruit cultures. The specificity of the obtained serum was confirmed by immunoelectroblotting. The resulting serum was used for indirect enzyme-linked immunosorbent assay, as well as for immunoassay ("sandwich") of a commercial test system manufactured by Loewe (Germany). As a result, plum pox virus was detected in six regions of Ukraine, the part of infected plants of stone fruit trees from the studied regions is 30%, which is a serious threat to our country's horticultural industry, and needs further molecular genetic diagnostics.

Novel salivary gland allergens from tropical mosquito species and IgE reactivity in allergic patients

BackgroundMosquito allergy is common in tropical countries but remains under-diagnosed. This may be due to the lack of knowledge and diagnostic tools for tropical mosquito allergens. ObjectiveWe aimed to characterize allergens from tropical mosquito species and investigate IgE reactivity in mosquito-allergic patients to the salivary gland proteins from these mosquitoes. MethodsSalivary gland extract (SGE) from 4 mosquito species, highly distributed in the tropics, including Aedes aegypti, Aedes albopictus, Culex quinquefasciatus, and Anopheles dirus b, were studied. SGE-specific IgE and IgG ELISA were developed, and serum from 64 mosquito-allergic and 22 non-allergic healthy control subjects was assayed. Further investigations using IgE-immunoblots followed by mass spectrometry analysis were performed to identify and characterize allergens from each species. ResultsMosquito-allergic subjects have detectable serum IgE to SGE derived from local mosquito species, while the IgE levels to Aedes communis using commercially available ELISA were mostly minimal. IgE-immunoblot analysis and mass spectrometry identified 5 novel mosquito allergens from A. albopictus (Aed al 2, Aed al 3), C. quinquefasciatus (Cul q 2.01, Cul q 3), and A. dirus b (Ano d 2). Interestingly, 4 of the 5 new allergens belong to the D7 protein family. Conclusions & clinical relevanceFive novel allergens from 3 tropical mosquito species were characterized. The majority of mosquito-allergic subjects who live in the tropics have IgE reactivity to these allergens. Our study paves the way for the development of diagnostic tests, component-resolved diagnostics, and future immunotherapy for mosquito allergy in tropical countries.

DOP14 Modelling of the relationship between infliximab exposure, faecal calprotectin, and endoscopic remission in patients with Crohn’s disease

Abstract Background Less than 50% of patients with Crohn’s disease (CD) starting infliximab (IFX) therapy achieve endoscopic remission (ER). Evidence for the benefits of pharmacokinetic (PK) and pharmacodynamic (PD) monitoring remains scarce. We aimed to develop a population (pop)PK/PD model to characterise the IFX dose-exposure-biomarker-response (faecal calprotectin [fCal] and ER) relationship in patients with CD. Methods Analyses were performed using data of a phase 4 dose-escalation study (TAILORIX). Patients started standard 5 mg/kg IFX induction therapy at weeks [w]0, 2 and 6. From w14 through w54, the IFX dose could be irreversibly doubled based on one of the three monitoring algorithms.1 Endoscopies were performed at w0, 12 and 54. Three sequential models were developed: A 2-compartment popPK model linking IFX dose to exposure, an indirect response popPK-PD model describing the inhibitory effect of IFX exposure on fCal, and a first-order Markov popPD model linking fCal to transitions between states of ER (CD endoscopic index of severity &amp;lt;3), no ER and dropout (Figure 1). All modelling and simulation were performed using NONMEM 7.4. Results The study included 116/122 (95%) patients with CD enrolled in TAILORIX who had ≥1 detectable IFX serum concentration. In the developed models, it was shown that IFX clearance increased with increasing fCal, decreasing albumin, increasing CD activity index and presence of antibodies to IFX (transiently). Baseline fCal increased with increasing CRP and decreasing platelet count. Lower fCal increased probability of attaining ER and decreased probability of losing ER. Probability of dropping out given an earlier state of absence of ER increased with elapsing time. Simulations of 150 000 patients receiving 5, 7.5 or 10 mg/kg IFX (1:1:1) resulted in a flat dose–response curve due to large interindividual variability in PK and PD (Figure 2, top panels). The predicted fraction of patients achieving ER at w12 was 45.1% [30.3–60.5] (median [IQR]) when on 5 mg/kg IFX (~46.4% observed in data). However, simulations of 10 mg/kg IFX induction doses predicted only a slight increase in the fraction of patients achieving ER at w12 to 47.5% [32.0–62.6]. This minor benefit at the population level argues against systematic 10 mg/kg induction dosing in all patients. A similar observation was done during maintenance therapy, where 70.8% [62.6–75.5] of all simulated patients maintained ER at w54 (~72.2% observed in data) (Figure 2, right panels). Conclusion Model-informed infliximab dose optimisation towards a predefined fCal concentration—while accounting for PK and PD variability—may improve the effectiveness of infliximab therapy (eg. 64% chance of ER at w12 ~100 μg/g fCal at w6). Reference

Population-based estimates of humoral autoimmunity from the U.S. National Health and Nutrition Examination Surveys, 1960-2014.

ObjectiveBased on US National Health and Nutrition Examination Survey (NHANES) data, we attempted to provide an unbiased, population-based estimate of autoantibody prevalence overall and by age and sex.MethodsUS autoantibody prevalence estimates for detectable rheumatoid factor, anti-thyroglobulin, anti-thyroperoxidase, anti-transglutaminase, anti-endomysial, anti-GAD65, antinuclear autoantibodies, and autoantibodies to extractable nuclear antigens were estimated from the 1960–1962 National Health Examination Survey, NHANES III (1988–1994), and the NHANES 1999–2014 cross-sectional surveys. Survey design variables and sample weights were used to account for differential probabilities of selection within the complex survey design. Data analysis used SASTM and SUDAAN™ software. US Census Bureau data were used to estimate the absolute numbers of persons with autoantibodies.ResultsNHANES III data show that the overall US prevalence of having a detectable serum autoantibody is substantial in adults, in both women and men. Thyroid autoantibodies were present in 18% of US adults (31 million persons) including 10% of younger adults and 25% of older persons. Overall autoantibody prevalences increased significantly with age: 32% of US adults 60+ years of age (12.8 million persons) had at least one of the four autoantibodies rheumatoid factor, anti-thyroglobulin, anti-thyroperoxidase, or anti-tissue transglutaminase. Older women had higher levels of autoantibodies, but this was a relative difference. Autoantibody prevalence in both sexes was substantial (women 39%; men 22%). Fourteen percent of adults 60+ years of age have multiple autoantibodies.ConclusionsAutoantibodies are present in a significant fraction of the general population, especially in older adults and women relative to men. Although all known clinically significant autoantibodies were not analyzed, these data provide an important population perspective on the scope and magnitude of humoral autoimmunity in the US. This is vital for prevention efforts to reduce autoimmune disease and helps clarify the potential impact of autoimmunity on the general population.

Significance of 5-S-Cysteinyldopa as a Marker for Melanoma.

Melanoma is one of the most lethal and malignant cancers and its incidence is increasing worldwide, and Japan is not an exception. Although there are numerous therapeutic options for melanoma, the prognosis is still poor once it has metastasized. The main concern after removal of a primary melanoma is whether it has metastasized, and early detection of metastatic melanoma would be effective in improving the prognosis of patients. Thus, it is very important to identify reliable methods to detect metastases as early as possible. Although many prognostic biomarkers (mainly for metastases) of melanoma have been reported, there are very few effective for an early diagnosis. Serum and urinary biomarkers for melanoma diagnosis have especially received great interest because of the relative ease of sample collection and handling. Several serum and urinary biomarkers appear to have significant potential both as prognostic indicators and as targets for future therapeutic methods, but still there are no efficient serum and urinary biomarkers for early detection, accurate diagnosis and prognosis, efficient monitoring of the disease and reliable prediction of survival and recurrence. Levels of 5-S-cysteinyldopa (5SCD) in the serum or urine as biomarkers of melanoma have been found to be significantly elevated earlier and to reflect melanoma progression better than physical examinations, laboratory tests and imaging techniques, such as scintigraphy and echography. With recent developments in the treatment of melanoma, studies reporting combinations of 5SCD levels and new applications for the treatment of melanoma are gradually increasing. This review summarizes the usefulness of 5SCD, the most widely used and well-known melanoma marker in the serum and urine, compares 5SCD and other useful markers, and finally its application to other fields.

Cocirculation of Two Orthohantavirus Species in Small Mammals of the Northwestern Ukraine.

Rodent-borne hantaviruses have been reported in many of the countries surrounding Ukraine; however, to date we have no knowledge of the viral strains circulating in Ukraine within reservoirs such as the striped field mouse (Apodemus agrarius), the yellow-necked field mouse (Apodemus flavicollis), and the bank vole (Myodes glareolus). To determine the prevalence of hantaviruses in Ukraine, we captured 1,261 mammals, of which 1,109 were rodents, in 58 field sites within the province of Volyn in western Ukraine. Foci of the striped field mouse tended to occur in the eastern and southern parts of the province, whereas the bank vole were clustered in western and northern regions. The striped field mouse and bank vole had detectable serum antibodies to Puumala virus (PUUV) or Dobrava virus (DOBV) antigens at 7% or 2%, respectively, using an indirect immunofluorescence assay. Antibody prevalence among the bank vole males and females was equivalent, whereas for the striped field mouse, the prevalence among males was 5% versus 1% for females. In two bank vole specimens, we were able to detect partial nucleotide sequences that showed identity to PUUV. In summary, this study suggests that two human pathogens, PUUV and DOBV, cocirculate in the bank vole and the striped field mouse, respectively, in Ukraine. Future studies will focus on new rodent collections that will enable obtaining the complete genome sequences of the PUUV and DOBV strains circulating in Ukraine to provide guidance on the design of optimal molecular diagnostics that can enable insight into the potential contribution of hantaviruses to human disease in Ukraine.

Clinical features of seronegative, but CSF antibody-positive, anti-NMDA receptor encephalitis.

ObjectiveTo determine the frequency of anti-NMDA receptor encephalitis without detectable serum NMDAR antibodies and to compare the clinical features of these patients with those with NMDAR antibodies in serum and CSF.MethodsThis is a retrospective assessment of serum antibody status and clinical features of 489 patients with anti-NMDAR encephalitis, defined by the presence of NMDAR antibodies in the CSF, and available paired serum/CSF samples examined at Hospital Clínic-Institut d’Investigacions Biomèdiques August Pi I Sunyer, Barcelona, between January 2007 and December 2017. NMDAR antibodies were determined with rat brain immunostaining, in-house cell-based assay (CBA), and a commercial CBA. Patients were considered seronegative if NMDAR antibodies were undetectable with the 3 indicated techniques.ResultsSerum NMDAR antibodies were not detected in 75 of 489 (15%) patients. Compared with the 414 seropositive patients, the seronegative were older (23.5 years [interquartile range (IQR): 17–43] vs 20.5 [IQR: 14–31]; p < 0.0001) and less frequently women (39 [52%] vs 313 [76%]; p < 0.001) and had less tumors (6 [9%] vs 128 [32%]; p < 0.001). In multivariate analysis, older age at diagnosis (odds ratio [OR]: 1.35 [per decade]; 95% confidence interval [CI]: 1.10–1.67), absence of tumor (OR: 0.14; 95% CI: 0.05–0.43), and less need for intensive care unit admission (OR: 0.35; 95% CI: 0.18–0.69) were independent variables associated with the absence of serum NMDAR antibodies. Time to diagnosis, treatment with immunotherapy, relapses, and outcome were similar in seronegative and seropositive patients.ConclusionsNMDAR antibodies are not detected in the serum of 15% of the patients with anti-NMDAR encephalitis. These patients appear to be older and have milder neurologic symptoms with less frequency of tumors.

Methotrexate effect on immunogenicity and long-term maintenance of adalimumab in axial spondyloarthritis: a multicentric randomised trial

ObjectivesAnti-drug antibodies (ADA) are responsible for decreased adalimumab efficacy in axial spondyloarthritis (SpA). We aimed to evaluate the ability of methotrexate (MTX) to decrease adalimumab immunisation.MethodsA total of 110 patients...

Detection Serum Antibodies for TORCH Infections during Aborted Pregnant Women in Fallujah, Iraq

Detection Serum Antibodies for TORCH Infections during Aborted Pregnant Women in Fallujah, Iraq

Orally consumed cannabinoids provide long-lasting relief of allodynia in a mouse model of chronic neuropathic pain.

Chronic pain affects a significant percentage of the United States population, and available pain medications like opioids have drawbacks that make long-term use untenable. Cannabinoids show promise in the management of pain, but long-term treatment of pain with cannabinoids has been challenging to implement in preclinical models. We developed a voluntary, gelatin oral self-administration paradigm that allowed male and female mice to consume ∆9-tetrahydrocannabinol, cannabidiol, or morphine ad libitum. Mice stably consumed these gelatins over 3 weeks, with detectable serum levels. Using a real-time gelatin measurement system, we observed that mice consumed gelatin throughout the light and dark cycles, with animals consuming less THC-gelatin than the other gelatin groups. Consumption of all three gelatins reduced measures of allodynia in a chronic, neuropathic sciatic nerve injury model, but tolerance to morphine developed after 1 week while THC or CBD reduced allodynia over three weeks. Hyperalgesia gradually developed after sciatic nerve injury, and by the last day of testing, THC significantly reduced hyperalgesia, with a trend effect of CBD, and no effect of morphine. Mouse vocalizations were recorded throughout the experiment, and mice showed a large increase in ultrasonic, broadband clicks after sciatic nerve injury, which was reversed by THC, CBD, and morphine. This study demonstrates that mice voluntarily consume both cannabinoids and opioids via gelatin, and that cannabinoids provide long-term relief of chronic pain states. In addition, ultrasonic clicks may objectively represent mouse pain status and could be integrated into future pain models.

Schmallenberg virus neutralising antibody responses in sheep

BackgroundSchmallenberg virus (SBV) is a midge borne virus of cattle and sheep. Infection is typically asymptomatic in adult sheep but fetal infection during pregnancy can result in abortion, stillbirth, neurological disorders and malformations of variable severity in newborn animals. It was first identified in Germany and the Netherlands in 2011 and then circulated throughout Europe in 2012 and 2013. Circulation in subsequent years was low or non-existent until summer and autumn 2016, leading to an increased incidence of deformed newborn lambs and calves in 2016–17. This study reports SBV circulation in October 2016 within a group of 24 ewes and 13 rams. The ewes were monitored at 3 times points over an 11 week period (September to December 2016).ResultsMost ewes displayed an increase in SBV VNT with antibody titre increases greater in older, previously exposed ewes. Two ewes had SBV RNA detectable by RT-qPCR, one on 30/09/16 and one on 04/11/16. Of these ewes, one had detectable serum SBV RNA (indicating viraemia) despite pre-existing antibody. The rams had been previously vaccinated with a commercial inactivated SBV vaccine, they showed minimal neutralising antibody titres against SBV 8 months post-vaccination and all displayed increased titre in October 2016.ConclusionThis data suggests that SBV circulated for a minimum period of 5 weeks in September to October 2016 in central England. Ewes previously exposed to virus showed an enhanced antibody response compared to naïve animals. Pre-existing antibody titre did not prevent re-infection in at least one animal, implying immunity to SBV upon natural exposure may not be life-long. In addition, data suggests that immunity provided by killed adjuvanted SBV vaccines only provides short term protection (< 8 months) from virus.

Detection of serum soluble HLA-G levels in patients with acute ischemic stroke: A pilot study

The aim of this study was to investigate the potential role of soluble Human Leukocyte Antigen-G (sHLA-G) molecules as biomarkers predicting outcome in acute ischemic stroke (AIS). Serum levels of total sHLA-G (sHLA-G1/HLA-G5) and its soluble isoforms sHLA-G1 and HLA-G5/G6 were measured by enzyme-linked immunosorbent assay (ELISA) in 92 AIS patients and healthy donors (HD). Incidence of hemorrhagic transformation (HT), size of final infarct volume (FIV) and clinical outcome at 3 months were recorded in AIS patients. Detectable serum levels of sHLA-G1/HLA-G5, HLA-G5/G6 and sHLA-G1 were present in a small proportion of AIS patients (26.1%, 17.4% and 16.3%, respectively) and HD (12.5%, 10.7% and 10.7%, respectively) and were more elevated in AIS patients without HT than in those with HT (p < 0.01; p < 0.05; p < 0.01, respectively). HT was less frequent (p < 0.01) in AIS patients with measurable serum concentrations of sHLA-G1/HLA-G5 and HLA-G5/G6. Serum levels of sHLA-G1/HLA-G5 and sHLA-G1 were inversely correlated to FIV (p < 0.02), whereas good outcome was more common (p < 0.01) in AIS patients with detectable serum concentrations of sHLA-G1/HLA-G5. Taken together, these findings suggest that total sHLA-G could exert a protective effect in a subset of AIS patients, irrespective of its soluble isoforms sHLA-G1 and HLA-G5/G6, and indicate that the prognostic value of serum levels of sHLA-G remains to be established.

Double-Blind, Randomized Study of Canakinumab Treatment in Pediatric and Young Adult Patients with Sickle Cell Anemia

Background: Sickle cell anemia (SCA) is a monogenic disease resulting in polymerization of hemoglobin in hypoxic conditions. This leads to red blood cell (RBC) membrane damage and sickling, causing vaso-occlusion and hemolysis. Continual, excessive release of lysed RBC contents within the vascular space can activate the inflammasome, a multiprotein oligomer that promotes maturation and secretion of pro-inflammatory cytokines, including interleukin 1-beta (IL-1β). The intravascular inflammation associated with SCA, e.g., increased serum c-reactive protein (CRP) and absolute counts of neutrophils and monocytes, is predictive of long-term morbidity and mortality. Inflammation is a major component of many of the clinical complications of SCA, including vaso-occlusive pain episodes, acute chest syndrome, vascular-endothelial dysfunction, renal disease and other forms of end organ damage. Standard of care for SCA is hydroxyurea, which augments fetal hemoglobin levels and may have some anti-inflammatory effects by reducing neutrophil and monocyte counts. Canakinumab is a fully human monoclonal antibody targeting IL-1ß and blocking its downstream pro-inflammatory activities with potential to ameliorate the inflammatory complications of SCA. Objective:To clinically validate in pediatric and young adult SCA patients the hypothesis that IL-1ß blockade by canakinumab is safe and provides clinical benefits. Methods: A multi-center, randomized, parallel group, double-blind, placebo-controlled trial recruited SCA patients (HbSS or HbS/ß0thalassemia) with history of ≥2 major pain episodes/year, screening baseline detectable pain (using pain e-diaries) and serum high sensitivity CRP level ≥1.0 mg/L. Patients were randomized with 1:1 ratio to receive six monthly s.c. injections of either canakinumab 300 mg (4 mg/kg for patients ≤40 kg) or placebo. The concurrent use of hydroxyurea was a stratification factor at randomization. Outcomes were measured at baseline and at weeks 4, 8, 12, 16, 20, 24, after which all patients moved to open label canakinumab treatment for additional 6 months. Electronic patient reported outcomes included daily pain intensity with a 0-10 cm visual analog scale, school/work absences secondary to SCA, fatigue and analgesic use. The primary outcome was change from baseline in the 4-week average daily pain intensity at week 12. Other secondary and exploratory outcomes included daily activity measured by wrist actigraphy, rate of hospitalization and adverse events, serious adverse events, transcranial Doppler velocities, percent oxygen saturation and laboratory markers of inflammation and hemolysis. Results: A planned interim analysis for futility and safety was performed on the first 30 enrolled patients (canakinumab, n=16; placebo, n=14), of whom 26 patients completed the Week 12 assessments (canakinumab, n=14; placebo, n=12), and 13 patients completed the Week 24 assessments. Enrolled patients (median age 17 years, range 12-20; 19 male, 11 female) were evenly distributed between treatment arms. All except one patient were maintained on a stable hydroxyurea regimen. Baseline overall disease activity levels (median, [range]) included average daily pain 3.93 [0.29, 6.57]; high sensitivity CRP 3.93 mg/L [1, 64.7]; transcranial Doppler velocities 85.0 m/s [23, 267]; hemoglobin 94.8 g/L [73.5, 121]. Futility criteria were not met and no canakinumab-associated safety issues were identified in this first interim analysis. Conclusions: Canakinumab was well tolerated and not associated with any major side effects in SCA. Results from a second interim analysis of study outcomes for all currently enrolled patients (n=49) completing the blinded, 24-week treatment period will be available in November 2019. Disclosures Rees: Agios: Other: Grants; TauRx (methylene blue): Other: Data monitoring committees; Astra Zeneca (ticagrelor): Other: Data monitoring committees; Novartis: Other: Strategic advisory role,Principal investigator,sickle cell disease2.6 Investigator; Emmaus: Other: Strategic advisory role; Celgene: Other: Strategic advisory role; Global Blood Therapeutics: Other: Strategic advisory role; Alnylam: Other: Principal investigator. Dampier:Micelle Biopharma: Consultancy, Research Funding; Merck: Research Funding; Hudson Publishing Company: Consultancy; Global Blood Therapeutics: Consultancy; Ironwood: Consultancy; Epizyme: Consultancy; Modus Therapeutics: Consultancy; Pfizer: Consultancy, Research Funding; Novartis: Consultancy, Research Funding. Mahlangu:Sanofi Genzyme: Research Funding, Speakers Bureau; Pfizer: Consultancy, Research Funding, Speakers Bureau; Takeda: Consultancy, Honoraria, Speakers Bureau; Novartis: Research Funding; Baxalta: Consultancy, Research Funding, Speakers Bureau; LFB: Consultancy; Biomarin: Research Funding; uniQure: Research Funding; Spark: Consultancy, Speakers Bureau; Chugai: Consultancy; CSL Behring: Consultancy, Research Funding, Speakers Bureau; Freeline Therapeutics: Research Funding; NovoNordisk: Consultancy, Research Funding, Speakers Bureau; Roche: Consultancy, Research Funding, Speakers Bureau; Shire: Consultancy, Research Funding, Speakers Bureau; Sobi: Research Funding, Speakers Bureau; World Federation of Haemophilia: Speakers Bureau. Mortier:Novartis Pharma AG: Employment. McNamara:Novartis Pharma AG: Employment. Li:Novartis Pharma AG: Employment. Oliver:Novartis Pharma AG: Employment, Equity Ownership. OffLabel Disclosure: canakinumab use in the treatment of sickle cell anemia.

Serum and urinary biomarkers for detection and active surveillance of prostate cancer.

To provide a comprehensive review of the available biomarkers for the detection and active surveillance of prostate cancer and simplify decision-making while choosing between them. The limitations of PSA and mpMRI and the invasive nature of prostate biopsy has led to a constant search for serum and urinary biomarkers for both the detection and monitoring during active surveillance of prostate cancer. 4K, PHI and PCA3 have been validated in prospective clinical trials for initial detection of prostate cancer and recent evidence points to potential differentiation between indolent and aggressive cancer. However, the usage in monitoring tumor dynamics is debatable because of lack of conclusive evidence. The answer to the existing problems lies in high-quality studies to establish definitive evidence and also to help choose between the plethora of biomarkers available today. Despite the advancements in innovation and usage of biomarkers in prostate cancer, there exists tremendous potential in improving them to fulfil the unmet need that exists today. Studies to establish conclusive evidence and integration with imaging can tremendously aid diagnosis and monitoring.

An update on the management of low-risk differentiated thyroid cancer.

Low-risk papillary cancers, which represent the vast majority of thyroid cancers diagnosed today, do not require aggressive treatment or follow-up. Initial treatment consists of a total thyroidectomy without prophylactic lymph node dissection. A hemithyroidectomy is an alternative in some patients with an intrathyroidal tumor and with a normal contralateral lobe at pre-operative neck ultrasonography. The use of post-operative radioiodine should be restricted to selected patients. Follow-up at 6-18 months is based on serum thyroglobulin (Tg), Tg-antibody determination and neck ultrasonography. In the absence of any abnormality (excellent response to treatment), the risk of recurrence is extremely low and follow-up may consist of serum TSH monitoring that is maintained in the normal range, and a Tg and Tg-antibody titer determination every year. There is no need for referral to a specialized center. In patients with detectable serum Tg or detectable Tg antibodies, the trend over time of these markers on levothyroxine treatment will dictate subsequent follow-up: a decreasing trend is reassuring, but an increasing trend should lead to imaging, starting with neck ultrasonography.

1551. Systemic Tobramycin Absorption Resulting from Antibiotic-Impregnated Cement Spacers for the Treatment of Prosthetic Joint Infection

BackgroundAntibiotic-impregnated cement spacer (ACS) placement has been a cornerstone of two-stage surgical management of prosthetic hip and knee infection for decades. Utilized antibiotics have included aminoglycosides and vancomycin. Pharmacokinetic modeling studies have described peak systemic levels within the first 24–48 hours post-operatively, followed by rapid clearance. While this systemic exposure was previously felt insufficient to cause organ toxicity, a few studies have described antibiotic-induced nephrotoxicity.MethodsWe prospectively enrolled patients with prosthetic hip or knee infection, and subsequent ACS placement, containing vancomycin and tobramycin, from October 2017 to February 2019, at Allegheny General Hospital. Risk factors for post-operative nephrotoxicity, including patient comorbidities, receipt of potentially nephrotoxic medications, estimated creatinine clearance (CrCl), perioperative hypotension, total spacer tobramycin dosage, and post-operative day 1 (POD1) and 3 (POD3) serum tobramycin levels were recorded. Patients who had antibiotic cement spacer exchange, or had received systemic aminoglycoside therapy, were excluded.ResultsThirteen patients were enrolled, comprising 4 hip and 9 knee ACS, with respective median (interquartile range (IQR)) tobramycin cement dosages of 3.8 (2.86–4.58) and 4.8 (4.8–9.6) grams. Tobramycin levels were measured at a median 16.5 and 60.7 hours on POD1 and POD3, respectively. Three hip and six knee ACS had respective, detectable POD1 median serum tobramycin levels of 0.6 (0.38–1.20) and 0.8 (0–0.8) μg/mL; three knees, but no hip ACS had detectable POD3 serum tobramycin levels. Six of the nine patients with detectable POD1 serum tobramycin levels had a CrCl of less than or equal to 65 mL/minute (figure), while each patient with detectable POD3 levels had a CrCl of less than 45 mL/minute. No significant changes in baseline CrCl were identified. A relationship between tobramycin cement dosage and detectable serum tobramycin levels was not observed.ConclusionLow baseline CrCl, but not the total tobramycin dosage or other nephrotoxicity risk factors, may be the single most reliable predictor of detectable postoperative systemic tobramycin levels in patients who have received hip or knee ACS. Disclosures All authors: No reported disclosures.

2278 Rapidly Progressive Hepatitis C After Liver Transplantation Treated With Glecaprevir/Pibrentasvir

INTRODUCTION: Hepatitis C recurrence following liver transplantation occurs in all patients with chronic HCV infection who have detectable serum HCV RNA levels prior to transplant. Less than 10% of these patients develop an acute and severe phenotype called fibrosing cholestatic hepatitis, which often involves fibrosis, rapid graft loss and decreased survival. The introduction of direct-acting antiviral agents (DAAs) have changed the paradigm of treatment of these patients. CASE DESCRIPTION/METHODS: A 62-year-old woman with a medical history of hepatitis C infection, hepatocellular carcinoma status post orthotropic liver transplantation, diabetes mellitus and hypertension who was hospitalized for fatigue and elevated liver chemistries following her liver transplantation. Laboratory tests showed a white cell count 6.67 × 103/μL, creatinine 1.1 mg/dL, aspartate aminotransferase 592 U/L, alanine aminotransferase 504U/L, alkaline phosphatase 312 U/L, bilirubin 3.5 mg/dL, albumin 2.9 g/dL. Acute hepatitis work up showed a positive hepatitis C virus antibodies with genotype 1B, with a viral load of 80 million IU/mL HCV RNA. HBsAg, HBc IgG, HBc IgM, and hepatitis A virus IgM were negative. Evaluation for Epstein-Barr virus, cytomegalovirus and herpes simplex virus were negative. Ultrasound of the abdomen revealed that the liver is normal in size, echotexture and contours. No focal hepatic lesions. Normal hepatic blood flow. The patient underwent liver biopsy that showed lymphocytic portal inflammation with frequent lobular apoptosis consistent with active chronic hepatitis C (MHAI: 5-6/18). Mild portal fibrosis (ISHAK FIBROSIS STAGE: 1/6) and minimal evidence of acute t cell-mediated rejection (rejection activity index: 1/9). During the patient hospitalization her liver chemistries significantly worsened and peaked to aspartate aminotransferase 740 U/L, alanine aminotransferase 511U/L, alkaline phosphatase 312 U/L, bilirubin 3.5 mg/dL. We decided to start the patient on Glecaprevir/Pibrentasvir for acute and severe hepatitis. Fourteen days after starting Glecaprevir/Pibrentasvir, the patient viral load decreased to 782 IU/mL HCV RNA and normalized liver chemistries with AST19 and ALT 27. The patient denied any adverse events due to the treatment. DISCUSSION: To our knowledge, this is the first case report of treating early and aggressive form of HCV recurrence with Glecaprevir/Pibrentasvir. The dramatic improvement of the patient suggest that DAA might be safe and effective in this situation.

High Incidence of Moderately Reduced Renal Function and Lead Bioaccumulation in Agricultural Workers in Assin South District, Ghana: A Community-Based Case-Control Study.

Background The quest to enhance agricultural productivity and crop yields has led to increased use of agrochemicals on a global scale. Long-term use of these agrochemicals may be associated with adverse health implications. Objective To assess haematological indices, renal function, heavy metal bioaccumulation in farmers and sprayers, and their use of personal protective equipment (PPE). Materials and Methods This community-based case-control study was conducted from January 2018 to June 2018 in the Assin South District, Central Region, Ghana. A total of 144 participants were conveniently sampled: 83 agricultural workers (cases) and 61 indigenes with no direct exposure to agrochemicals (controls). Structured questionnaire was used to obtain demographic data as well as agricultural work practices followed by cases. Venous blood samples were drawn from participants and used for estimating full blood count and renal function (serum creatinine (CRE), blood-urea nitrogen (BUN), BUN : CRE ratio, and estimated GFR (eGFR)). Serum lead, arsenic, and cadmium levels were estimated using the Varian AA 240FS atomic spectrometer in an acetylene-air flame. Results The median RBC (4.49 vs. 4.92 × 1012/L), haemoglobin (12.50 vs. 13.70 g/dL), and platelet (220.00 vs. 268.00) counts were significantly lower in cases. A significantly higher proportion of cases were classified as anaemic or having microcytic cells compared to controls. Also, serum urea (4.08 vs. 3.41; p=0.0009), creatinine (108.10 vs. 101.10; p=0.0286), and BUN : CRE ratio (19.75 vs. 17.84) were significantly higher in cases. Additionally, 18.1% of cases were classified as having moderately reduced renal function compared to only 6.6% of controls. Moreover, a significantly higher proportion of cases had detectable serum lead (55.6% vs. 16.4%) and arsenic (53.1% vs. 9.8%) levels compared to controls. However, on average, 80% of agricultural workers did not use personal protective equipment (PPE) when applying agrochemicals; 84.3% of used agrochemical containments were discarded near the river/canal. Conclusion Neglect of the use of PPE may be predisposing the agrochemical workers and community to lead and arsenic bioaccumulation with a consequent reduced haematological and renal function.