Investigating the time to blood culture positivity: why does it take so long?

Bloodstream infections (BSIs) are one of the most serious infections investigated by microbiologists. However, the time to detect a BSI fails to meet the rapidity required to inform clinical decisions in real time. Blood culture (BC) is considered the gold standard for diagnosing bloodstream infections.

Rapid determination of antimicrobial susceptibility of Gram-negative bacteria from clinical blood cultures using a scattered light-integrated collection device.

A bloodstream infection (BSI) presents a complex and serious health problem, a problem that is being exacerbated by increasing antimicrobial resistance (AMR). The current turnaround times (TATs) for most antimicrobial susceptibility testing (AST) methods offer results retrospective of treatment decisions, and this limits the impact AST can have on antibiotic prescribing and patient care. Progress must be made towards rapid BSI diagnosis and AST to improve antimicrobial stewardship and reduce preventable deaths from BSIs.

Analysis of the ARTIC V4 and V4.1 SARS-CoV-2 primers and their impact on the detection of Omicron BA.1 and BA.2 lineage-defining mutations.

The ARTIC protocol uses a multiplexed PCR approach with two primer pools tiling the entire SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) genome. Primer pool updates are necessary for accurate amplicon sequencing of evolving SARS-CoV-2 variants with novel mutations. The suitability of the ARTIC V4 and updated V4.

Box-Counting Dimension in One-Dimensional Random Geometry of Multiplicative Cascades.

We investigate the box-counting dimension of the image of a set under a random multiplicative cascade function . The corresponding result for Hausdorff dimension was established by Benjamini and Schramm in the context of random geometry, and for sufficiently regular sets, the same formula holds for the box-counting dimension. However, we show that this is far from true in general, and we compute explicitly a formula of a very different nature that gives the almost sure box-counting dimension of the random image () when the set comprises a convergent sequence.

Hepatitis delta infection among persons living with HIV in Europe.

Background And Aims: A high prevalence of hepatitis delta virus (HDV) infection, the most severe form of viral hepatitis, has been reported among persons living with HIV (PLWH) in Europe. We analysed data from a large HIV cohort collaboration to characterize HDV epidemiological trends across Europe, as well as its impact on clinical outcomes.

Methods: All PLWH with a positive hepatitis B surface antigen (HBsAg) in the Swiss HIV Cohort Study and EuroSIDA between 1988 and 2019 were tested for anti-HDV antibodies and, if positive, for HDV RNA.

Low Risk of Failing Direct-Acting Antivirals in People With Human Immunodeficiency Virus/Hepatitis C Virus From Sub-Saharan Africa or Southeastern Asia: A European Cross-Sectional Study.

Background: Several studies have reported suboptimal efficacy of direct-acting antivirals (DAAs) to treat hepatitis C virus (HCV) subtypes endemic to sub-Saharan Africa (SSA) and Southeastern Asia (SEA). The extent of this issue in individuals with human immunodeficiency virus (HIV)/HCV from SSA or SEA residing in Europe is unknown.

Methods: We retrospectively analyzed data from several prospective European cohorts of people living with HIV.

Direct Reprogramming of Cardiac Fibroblasts to Repair the Injured Heart.

Coronary heart disease is a leading cause of mortality and morbidity. Those that survive acute myocardial infarction are at significant risk of subsequent heart failure due to fibrotic remodelling of the infarcted myocardium. By applying knowledge from the study of embryonic cardiovascular development, modern medicine offers hope for treatment of this condition through regeneration of the myocardium by direct reprogramming of fibrotic scar tissue.

Effectiveness and Safety of Interferon-Free Direct-Acting Antiviral Hepatitis C Virus Therapy in HIV/Hepatitis C Virus Coinfected Individuals: Results From a Pan-European Study.

Objectives: To investigate the effectiveness, safety, and reasons for premature discontinuation of direct-acting antivirals (DAAs) in a diverse population of HIV/hepatitis C virus (HCV) coinfected individuals in Europe.

Methods: All HIV/HCV coinfected individuals in the EuroSIDA study that started interferon free DAA treatment between January 6, 2014, and January 3, 2018, with ≥12 weeks of follow-up after treatment stop were included in this analysis. Sustained virological response (SVR) was defined as a negative HCV-RNA result ≥12 weeks after stopping treatment (SVR12).

Improving the recovery and detection of bloodstream pathogens from blood culture.

Bloodstream infections (BSI) are growing in incidence and present a serious health threat. Most patients wait up to 48 h before microbiological cultures can confirm a diagnosis. Low numbers of circulating bacteria in patients with BSI mean we need to develop new methods and optimize current methods to facilitate efficient recovery of bacteria from the bloodstream.

Long-Term Study of Hepatitis Delta Virus Infection at Secondary Care Centers: The Impact of Viremia on Liver-Related Outcomes.

Background And Aims: Hepatitis delta virus (HDV) infection is associated with fast progression to liver cirrhosis and liver complications. Previous studies have, however, been mainly from tertiary care centers, with risk for referral bias toward patients with worse outcomes. Furthermore, the impact of HDV viremia per se on liver-related outcomes is not really known outside the human immunodeficiency virus co-infection setting.

Plasma FABP4 is associated with liver disease recovery during treatment-induced clearance of chronic HCV infection.

Direct-acting antivirals (DAAs) have dramatically improved the management of chronic hepatitis C (CHC). In this study, we investigated the effects of hepatitis C virus clearance on markers of systemic inflammation measured in plasma samples from CHC patients before, during and after DAA therapy. We identified a plasma soluble protein profile associated with CHC.

Clinical Outcomes in Persons Coinfected With Human Immunodeficiency Virus and Hepatitis C Virus: Impact of Hepatitis C Virus Treatment.

Background: A hepatitis C (HCV) cure is associated with changes in lipids and inflammatory biomarkers, but its impact on clinical endpoints among treated human immunodeficiency virus (HIV)/HCV coinfected persons is unclear.

Methods: People living with HIV from EuroSIDA with a known HCV status after January 2001 were classified into strata based on time-updated HCV RNA measurements and HCV treatment, as either HCV antibody-negative; spontaneously resolved HCV; chronic, untreated HCV; cured HCV (HCV RNA-negative); or HCV treatment failures (HCV RNA-positive). Poisson regression was used to compare incidence rates between HCV groups for end-stage liver disease (ESLD; including hepatocellular carcinoma [HCC]), non-acquired immunodeficiency virus defining malignancy (NADM; excluding HCC), and cardiovascular disease (CVD).

Establishing a hepatitis C continuum of care among HIV/hepatitis C virus-coinfected individuals in EuroSIDA.

Objectives: The aim of the study was to establish a methodology for evaluating the hepatitis C continuum of care in HIV/hepatitis C virus (HCV)-coinfected individuals and to characterize the continuum in Europe on 1 January 2015, prior to widespread access to direct-acting antiviral (DAA) therapy.

Methods: Stages included in the continuum were as follows: anti-HCV antibody positive, HCV RNA tested, currently HCV RNA positive, ever HCV RNA positive, ever received HCV treatment, completed HCV treatment, follow-up HCV RNA test, and cure. Sustained virological response (SVR) could only be assessed for those with a follow-up HCV RNA test and was defined as a negative HCV RNA result measured > 12 or 24 weeks after stopping treatment.

Discourses mapped by Q-method show governance constraints motivate landscape approaches in Indonesia.

Interpreting discourses among implementers of what is termed a "landscape approach" enables us to learn from their experience to improve conservation and development outcomes. We use Q-methodology to explore the perspectives of a group of experts in the landscape approach, both from academic and implementation fields, on what hinderances are in place to the realisation of achieving sustainable landscape management in Indonesia. The results show that, at a generic level, "corruption" and "lack of transparency and accountability" rank as the greatest constraints on landscape functionality.

Uptake of hepatitis C virus treatment in HIV/hepatitis C virus-coinfected patients across Europe in the era of direct-acting antivirals.

Background And Aims: To investigate the uptake of hepatitis C virus (HCV) therapy among HIV/HCV-coinfected patients in the pan-European EuroSIDA study between 2011 and 2016.

Methods: All HCV-RNA+ patients were included. Baseline was defined as latest of anti-HCV+, January 2011 or enrolment in EuroSIDA.

IL13Rα2 expression identifies tissue-resident IL-22-producing PLZF innate T cells in the human liver.

Innate lymphocytes are selectively enriched in the liver where they have important roles in liver immunology. Murine studies have shown that type I NKT cells can promote liver inflammation, whereas type II NKT cells have an anti-inflammatory role. In humans, type II NKT cells were found to accumulate in the gut during inflammation and IL13Rα2 was proposed as a marker for these cells.

The association between detected drug resistance mutations and CD4 T-cell decline in HIV-positive individuals maintained on a failing treatment regimen.

Background: To analyse the effect of drug resistance mutations (DRM) on CD4 T-cell (CD4) trends in HIV-positive people maintained on virologically failing antiretroviral therapy (ART).

Methods: Individuals from two large cohorts experiencing virological failure (VF) while maintained on ART with ≥1 CD4 count and ≥1 resistance test were included. CD4 slopes were estimated using linear mixed models.

Long-term effectiveness of unboosted atazanavir plus abacavir/lamivudine in subjects with virological suppression: A prospective cohort study.

Effectiveness data of an unboosted atazanavir (ATV) with abacavir/lamivudine (ABC/3TC) switch strategy in clinical routine are scant.We evaluated treatment outcomes of ATV + ABC/3TC in pretreated subjects in the EuroSIDA cohort when started with undetectable plasma HIV-1 viral load (pVL), performing a time to loss of virological response (TLOVR <50 copies/mL) and a snapshot analysis at 48, 96, and 144 weeks. Virological failure (VF) was defined as confirmed pVL >50 copies/mL.

The Human NK Cell Response to Yellow Fever Virus 17D Is Primarily Governed by NK Cell Differentiation Independently of NK Cell Education.

NK cells play an important role in the defense against viral infections. However, little is known about the regulation of NK cell responses during the first days of acute viral infections in humans. In this study, we used the live attenuated yellow fever virus (YFV) vaccine 17D as a human in vivo model to study the temporal dynamics and regulation of NK cell responses in an acute viral infection.

The future disease burden of hepatitis C virus infection in Sweden and the impact of different treatment strategies.

Unlabelled: OBJECTIVE. Recently, new highly effective direct-acting antivirals (DAAs) against hepatitis C virus (HCV) were introduced. Whether these will alleviate the anticipated increase of liver disease burden in Sweden is unknown, partly because high costs may restrict the use.

The dynamic relationship between innate immune biomarkers and interferon-based treatment effects and outcome in hepatitis C virus infection is altered by telaprevir.

Soluble CD14 (sCD14) and IL-18 are markers and mediators of the innate immune response, and their plasma levels candidate biomarkers of HCV treatment effects and outcome. Here, we retrospectively studied sCD14 and IL-18 over the course of interferon-based treatment of HCV genotype 1 infection, with the aim to investigate the impact of direct-acting antivirals (DAAs) on the dynamics and relationships between these biomarkers and treatment effects and outcome. Two cohorts were followed longitudinally; one treated with standard dual therapy of pegylated IFNα and ribavirin, and one cohort receiving triple therapy including Telaprevir.

High HCV treatment uptake in the Swedish HIV/HCV co-infected cohort.

Background: HCV co-infection is a leading cause of death in HIV-positive patients. Despite a strong indication for the treatment of HCV, treatment uptake is generally lower than in HCV mono-infected patients. The aim of this study was to determine the HCV treatment uptake and to define factors associated with initiation or deferral of HCV treatment in Swedish HIV/HCV co-infected patients.

Occasional spontaneous clearance of chronic hepatitis C virus in HIV-infected individuals.

The IL28B genotype has been found to have a strong influence on spontaneous clearance of acute HCV both in HCV mono- and HIV/ the HCV co-infected patients. Spontaneous clearance of chronic HCV without HCV treatment is rare. Here, we report on three chronic HCV cases co-infected with HIV with spontaneous clearance of their HCV infection, all with the IL28B CC genotype.

Strategies to manage hepatitis C virus (HCV) disease burden.

The number of hepatitis C virus (HCV) infections is projected to decline while those with advanced liver disease will increase. A modeling approach was used to forecast two treatment scenarios: (i) the impact of increased treatment efficacy while keeping the number of treated patients constant and (ii) increasing efficacy and treatment rate. This analysis suggests that successful diagnosis and treatment of a small proportion of patients can contribute significantly to the reduction of disease burden in the countries studied.