Evaluation of the accuracy of a multi-infection screening test based on a multiplex immunoassay targeting imported diseases common in migrant populations

Background: We aimed to evaluate the performance of a novel multiplex serological assay, able to simultaneously detect IgG of six infections, as a screening tool for imported diseases in migrants. Methods: Six panels of 40 (n = 240) anonymized serum samples with confirmed infections were used as positive controls to assess the multiplex assay's sensitivity. One panel of 40 sera from non-infected subjects was used to estimate the seropositivity cutoffs, and 32 non-infected sera were used as negative controls to estimate each serology's sensitivity and specificity. The multi-infection screening test was validated in a prospective cohort of 48 migrants from endemic areas.The sensitivity of the Luminex assay was calculated as the proportion of positive results over all positive samples identified by reference tests. The specificity was calculated using 32 negative samples. Uncertainty was quantified with 95 % confidence intervals using receiver operating characteristic analyses. Results: The sensitivity/specificity were 100 %/100 % for HIV (gp41 antigen), 97.5 %/100 % for Hepatitis B virus (HBV-core antigen), 100 %/100 % for Hepatitis C virus (HCV-core antigen), 92.5 %/90.6 % for strongyloidiasis [31-kDa recombinant antigen (NIE)], 97.5 %/100 % for schistosomiasis (combined serpin Schistosoma mansoni and S.haematobium antigens) and 95 %/90.6 % for Chagas disease [combined Trypanosoma cruzi kinetoplastid membrane protein-11 (KMP11) and paraflagellar rod proteins 2 (PFR2) antigens].In the migrant cohort, antibody response to the combination of the T.cruzi antigens correctly identified 100 % individuals, whereas HBV-core antigen correctly identified 91.7 % and Strongyloides-NIE antigen 86.4 %. Conclusions: We developed a new, robust and accurate 8-plex Luminex assay that could facilitate the implementation of screening programmes targeting migrant populations

A multi-country analysis of COVID-19 hospitalizations by vaccination status.

BackgroundIndividuals vaccinated against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), when infected, can still develop disease that requires hospitalization. It remains unclear whether these patients differ from hospitalized unvaccinated patients with regard to presentation, coexisting comorbidities, and outcomes.MethodsHere, we use data from an international consortium to study this question and assess whether differences between these groups are context specific. Data from 83,163 hospitalized COVID-19 patients (34,843 vaccinated, 48,320 unvaccinated) from 38 countries were analyzed.FindingsWhile typical symptoms were more often reported in unvaccinated patients, comorbidities, including some associated with worse prognosis in previous studies, were more common in vaccinated patients. Considerable between-country variation in both in-hospital fatality risk and vaccinated-versus-unvaccinated difference in this outcome was observed.ConclusionsThese findings will inform allocation of healthcare resources in future surges as well as design of longer-term international studies to characterize changes in clinical profile of hospitalized COVID-19 patients related to vaccination history.FundingThis work was made possible by the UK Foreign, Commonwealth and Development Office and Wellcome (215091/Z/18/Z, 222410/Z/21/Z, 225288/Z/22/Z, and 220757/Z/20/Z); the Bill & Melinda Gates Foundation (OPP1209135); and the philanthropic support of the donors to the University of Oxford's COVID-19 Research Response Fund (0009109). Additional funders are listed in the "acknowledgments" section

Antioxidant supplementation can reduce the survival costs of excess amino acid intake in honeybees

Over-consuming amino acids is associated with reduced survival in many species, including honeybees. The mechanisms responsible for this are unclear but one possibility is that excessive intake of amino acids increases oxidative damage. If this is the case, antioxidant supplementation may help reduce the survival costs of high amino acid intake. We tested this hypothesis in African honeybees (Apis mellifera scutellata) using the major antioxidant in green tea, epigallocatechin-3-gallate (EGCG). We first determined the dose-range of EGCG that improved survival of caged honeybees fed sucrose solution. We then provided bees with eight diets that differed in their ratio of essential amino acids (EAA) to carbohydrate (C) (0:1, 1:250, 1:100, 1:75, 1:50, 1:25, 1:10, 1:5 EAA:C) and also in their EGCG dose (0.0 or 0.4 mM). We found that bees fed sucrose only solution survived better than bees fed EAA diets. Despite this, bees preferred a diet that contained intermediate ratios of EAA:C (ca. 1:25), which may represent the high demands for nitrogen of developing nurse bees. EGCG supplementation improved honeybee survival but only at an intermediate dose (0.3–0.5 mM) and in bees fed low EAA diets (1:250, 1:100 EAA:C). That EGCG counteracted the lifespan reducing effects of eating low EAA diets suggests that oxidative damage may be involved in the association between EAAs and lifespan in honeybees. However, that EGCG had no effect on survival in bees fed high EAA diets suggests that there are other physiological costs of over-consuming EAAs in honeybees.A grant from the BBSRC, NERC, the Wellcome Trust, Defra, and the Scottish Government under the Insect Pollinators Initiative (BB/I000968/1).http://www.elsevier.com/locate/jinsphyshj201

Cholangiocarcinoma landscape in Europe: Diagnostic, prognostic and therapeutic insights from the ENSCCA Registry

Background and aims: Cholangiocarcinoma (CCA) is a rare and heterogeneous biliary cancer, with increasing incidence and related mortality. This study investigates the clinical course of CCA and subtypes (intrahepatic (iCCA), perihilar (pCCA), and distal (dCCA)) in a pan-European cohort. Methods: The ENSCCA Registry is a multicenter observational study. Patients with histologically-proven CCA diagnosis between 2010-2019 were included. Demographic, histomorphological, biochemical, and clinical studies were performed. Results: Overall, 2,234 patients were enrolled (male:female=1.29). iCCA (n=1,243) was associated with overweight/obesity (58.5%) and chronic liver diseases involving cirrhosis (12.6%) and/or viral hepatitis (10.4%); pCCA (n=592) with primary sclerosing cholangitis (8.8%); and dCCA (n=399) with choledocholithiasis (10.3%). At diagnosis, 42.2% of patients had local disease, 29.4% locally-advanced disease (LAD), and 28.4% metastatic disease (MD). Serum CEA and CA19-9 showed low diagnostic sensitivity (69.1% and 40.9% below cutoff, respectively), but their concomitant elevation was associated with increased risk of presenting with LAD [OR=2.16;95%CI:1.43-3.27] or MD [OR=5.88;95%CI:3.69-9.25]. Patients undergoing resection (50.3%) showed the best outcome, particularly with negative-resection margin (R0) [median overall survival (mOS)=45.1 months]; however, margin involvement (R1) [HR=1.92;95%CI:1.53-2.41;mOS=24.7 months] and lymph node invasion [HR=2.13;95%CI:1.55-2.94;mOS=23.3 months] compromised prognosis. Among patients with unresectable disease (49.6%), the mOS was 10.6 months for those receiving active palliative therapies, mostly chemotherapy (26.2%). Patients receiving best supportive care (20.6%) had mOS of 4.0 months, with iCCAs showing worst outcome compared to p/dCCAs. ECOG performance status [HR=1.52;95%CI:1.01-2.31], MD [HR=4.03;95%CI:1.82-8.92] and CA19-9 [HR=2.79;95%CI:1.46-5.33] were independently prognostic for OS. Conclusion: CCA is still diagnosed at advanced stage, a proportion of patients fail to receive cancer-specific therapies, and prognosis is dismal. Identification of preventable risk factors and implementation of surveillance in high-risk populations are required to decrease cancer-related mortality. Lay summary: This is, to date, the largest and more complete international (pan-European: 26 hospitals and 11 countries) observational study, in which the course of CCA is investigated, comparing the three subtypes based on the latest International Classification of Diseases 11th Edition (ICD-11) [i.e., intrahepatic (2C12), perihilar (2C18), or distal (2C15) affected bile ducts] (coming into effect in 2022). General and tumor-type specific features at diagnosis, risk factors, biomarker accuracy, as well as patient management and outcomes, among others, are presented and compared, outlining the current European scenario on the clinical state of CCA

Cholangiocarcinoma landscape in Europe: Diagnostic, prognostic and therapeutic insights from the ENSCCA Registry

Background & Aims: Cholangiocarcinoma (CCA) is a rare and heterogeneous biliary cancer, whose incidence and related mortality is increasing. This study investigates the clinical course of CCA and subtypes (intrahepatic [iCCA], perihilar [pCCA], and distal [dCCA]) in a pan-European cohort. Methods: The ENSCCA Registry is a multicenter observational study. Patients were included if they had a histologically proven diagnosis of CCA between 2010-2019. Demographic, histomorphological, biochemical, and clinical studies were performed. Results: Overall, 2,234 patients were enrolled (male/female=1.29). iCCA (n = 1,243) was associated with overweight/obesity and chronic liver diseases involving cirrhosis and/or viral hepatitis; pCCA (n = 592) with primary sclerosing cholangitis; and dCCA (n = 399) with choledocholithiasis. At diagnosis, 42.2% of patients had local disease, 29.4% locally advanced disease (LAD), and 28.4% metastatic disease (MD). Serum CEA and CA19-9 showed low diagnostic sensitivity, but their concomitant elevation was associated with increased risk of presenting with LAD (odds ratio 2.16; 95% CI 1.43-3.27) or MD (odds ratio 5.88; 95% CI 3.69-9.25). Patients undergoing resection (50.3%) had the best outcomes, particularly with negative-resection margin (R0) (median overall survival [mOS] = 45.1 months); however, margin involvement (R1) (hazard ratio 1.92; 95% CI 1.53-2.41; mOS = 24.7 months) and lymph node invasion (hazard ratio 2.13; 95% CI 1.55-2.94; mOS = 23.3 months) compromised prognosis. Among patients with unresectable disease (49.6%), the mOS was 10.6 months for those receiving active palliative therapies, mostly chemotherapy (26.2%), and 4.0 months for those receiving best supportive care (20.6%). iCCAs were associated with worse outcomes than p/dCCAs. ECOG performance status, MD and CA19-9 were independent prognostic factors. Conclusion: CCA is frequently diagnosed at an advanced stage, a proportion of patients fail to receive cancer-specific therapies, and prognosis remains dismal. Identification of preventable risk factors and implementation of surveillance in high-risk populations are required to decrease cancer-related mortality. Lay summary: This is, to date, the largest international (pan-European: 26 hospitals and 11 countries) observational study, in which the course of cholangiocarcinoma has been investigated, comparing the 3 subtypes based on the latest International Classification of Diseases 11th Edition (ICD-11) (i.e., intrahepatic [2C12], perihilar [2C18], or distal [2C15] affected bile ducts), which come into effect in 2022. General and tumor-type specific features at diagnosis, risk factors, biomarker accuracy, as well as patient management and outcomes, are presented and compared, outlining the current clinical state of cholangiocarcinoma in Europe