DNA methylation analysis on anal swabs for anal cancer screening in people living with HIV.

Introduction: High-resolution anoscopy (HRA) to prevent anal cancer is complex and screening capacity is limited. Previously, we showed that DNA methylation analysis of anal high-grade squamous intraepithelial lesions (HSIL) biopsies can distinguish between HSIL with an increased cancer risk, and HSIL with a low cancer risk, in which treatment may be safely withheld. Here, we assessed the performance of methylation analysis in anal swabs to identify patients with underlying HSIL with an increased cancer risk.

Identifying excessive length of antibiotic treatment duration for hospital-acquired infections: a semi-automated approach to support antimicrobial stewardship.

Background: Avoiding excessive antibiotic treatment duration is a fundamental goal in antimicrobial stewardship. Manual collection of data is a time-consuming process, but a semi-automated approach for data extraction has been shown feasible for community-acquired infections (CAI). Extraction of data however may be more challenging in hospital-acquired infections (HAI).

Lymphopenia is associated with broad host response aberrations in community-acquired pneumonia.

Objectives: Lymphopenia at hospital admission occurs in over one-third of patients with community-acquired pneumonia (CAP), yet its clinical relevance and pathophysiological implications remain underexplored. We evaluated outcomes and immune features of patients with lymphopenic CAP (L-CAP), a previously described immunophenotype characterized by admission lymphocyte count <0.724 × 10 cells/L.

Virological Failure After Switch to Long-Acting Cabotegravir and Rilpivirine Injectable Therapy: An In-depth Analysis.

Background: Long-acting (LA) injectable therapy with cabotegravir (CAB) and rilpivirine (RPV) is currently used as maintenance treatment for human immunodeficiency virus type 1, and has a low risk for virological failure (VF). Although the risk is low, the circumstances and impact of VF in the real-world setting merit further evaluation.

Methods: We performed an in-depth clinical, virological, and pharmacokinetic analysis on the reasons behind and the impact of VF during LA CAB/RPV therapy in 5 cases from the Netherlands.

Analytical validation and diagnostic performance of the ASCL1/ZNF582 methylation test for detection of high-grade anal intraepithelial neoplasia and anal cancer.

DNA methylation testing on biopsies can detect high-grade anal intraepithelial neoplasia (HGAIN) in need of treatment and anal cancer. This study aimed to analytically validate and determine the diagnostic performance of a newly developed multiplex quantitative methylation-specific PCR, PreCursor-M AnoGYN (RUO), combining ASCL1, ZNF582 and a reference (ACTB) in one assay. Analytical validation was performed on two qPCR devices using predefined quality criteria.

The Utility of Risk Factors to Define Complicated Staphylococcus aureus Bacteremia in a Setting With Low Methicillin-Resistant S. aureus Prevalence.

Introduction: Recommended duration of antibiotic treatment of Staphylococcus aureus bacteremia (SAB) is frequently based on distinguishing uncomplicated and complicated SAB, and several risk factors at the onset of infection have been proposed to define complicated SAB. Predictive values of risk factors for complicated SAB have not been validated, and consequences of their use on antibiotic prescriptions are unknown.

Methods: In a prospective cohort, patients with SAB were categorized as complicated or uncomplicated through adjudication (reference definition).

A national antimicrobial guide with local, customizable versions: how is it used? A two-year analysis.

Objectives: Guideline adherence is one of the most important objectives for antibiotic stewardship. The Dutch Working Party on Antibiotic Policy (SWAB) developed an online national guide (SWAB-ID) in 2006. Every Dutch hospital is offered the opportunity to customize the national version to their local context and distribute it through an independent website.

Perceptions of Rapid Antiretroviral Therapy Initiation Among Participants of The Netherlands Cohort Study on Acute HIV Infection.

Starting antiretroviral therapy (ART) same-day, or as soon as possible after HIV diagnosis is advised in guidelines worldwide. Especially during acute HIV infection (AHI), rapid ART start may be more urgent because of a higher risk of transmission or symptoms of acute retroviral syndrome. During this phase, rapid ART start may have additional benefits for viral reservoir size and host immunity.

Virological and immunological correlates of HIV posttreatment control after temporal antiretroviral therapy during acute HIV infection.

Objective: People with HIV rarely control viral replication after cessation of antiretroviral therapy (ART). We present a person with HIV with extraordinary posttreatment control (PTC) for over 23 years after temporary ART during acute HIV infection (AHI) leading to a new insight in factors contributing to PTC.

Design/methods: Viral reservoir was determined by HIV qPCR, Intact Proviral DNA Assay, and quantitative viral outgrowth assay.

Pneumonia pattern recognition on ultra-low-dose CT does not allow for a reliable differentiation between viral and bacterial pneumonia: A multicentre observer study.

Purpose: While a reliable differentiation between viral and bacterial pneumonia is not possible with chest X-ray, this study investigates whether ultra-low-dose chest-CT (ULDCT) could be used for this purpose.

Methods: In the OPTIMACT trial 281 patients had a final diagnosis of pneumonia, and 96/281 (34%) had one or more positive microbiology results: 60 patients viral pathogens, 48 patients bacterial pathogens. These 96 ULDCT's were blindly and independently evaluated by two chest radiologists, who reported CT findings, pneumonia pattern, and most likely type of pathogen.

Therapeutic Vaccination against Human Papillomavirus Type 16 for the Treatment of High-Grade Anal Intraepithelial Neoplasia in HIV+ Men.

Purpose: Anal cancer is increasing in HIV+ men who have sex with men (MSM). Treatment options for its precursor, high-grade anal intraepithelial neoplasia (HGAIN), are suboptimal. In this phase I to II dose-finding study, we assessed the safety and efficacy of the human papillomavirus type 16 (HPV16) synthetic long peptide vaccine (SLP-HPV-01) in HIV+ MSM with HPV16-positive HGAIN.

Population pharmacokinetic/pharmacodynamic target attainment of ceftriaxone 2 g once daily in non-critically ill hospitalized adult patients during the acute phase of infection.

Aims: Pharmacokinetic/pharmacodynamic target attainment of ceftriaxone is compromised in intensive care unit (ICU) patients and non-ICU hospitalized patients in Beira, Mozambique. Whether this also accounts for non-ICU patients in a high-income setting is unknown. We therefore assessed the probability of target attainment (PTA) of the currently recommended dosing regimen of 2 g every 24 h (q24h) in this patient group.

Limited Clinical Impact of Ultralow-Dose Computed Tomography in Suspected Community-Acquired Pneumonia.

Patients clinically suspected of community-acquired pneumonia (CAP) were randomized between ultralow-dose chest computed tomography ([ULDCT] 261 patients) and chest radiograph ([CXR] 231 patients). We did not find evidence that performing ULDCT instead of CXR affects antibiotic treatment policy or patient outcomes. However, in a subgroup of afebrile patients, there were more patients diagnosed with CAP in the ULDCT group (ULDCT, 106 of 608 patients; CXR, 71 of 654 patients; = .

The yield of chest X-ray or ultra-low-dose chest-CT in emergency department patients suspected of pulmonary infection without respiratory symptoms or signs.

Objective: The yield of pulmonary imaging in patients with suspected infection but no respiratory symptoms or signs is probably limited, ultra-low-dose CT (ULDCT) is known to have a higher sensitivity than Chest X-ray (CXR). Our objective was to describe the yield of ULDCT and CXR in patients clinically suspected of infection, but without respiratory symptoms or signs, and to compare the diagnostic accuracy of ULDCT and CXR.

Methods: In the OPTIMACT trial, patients suspected of non-traumatic pulmonary disease at the emergency department (ED) were randomly allocated to undergo CXR (1210 patients) or ULDCT (1208 patients).

Age-related changes in plasma biomarkers and their association with mortality in COVID-19.

Background: Coronavirus disease 2019 (COVID-19)-induced mortality occurs predominantly in older patients. Several immunomodulating therapies seem less beneficial in these patients. The biological substrate behind these observations is unknown.

Positive Impact of [18F]FDG-PET/CT on Mortality in Patients With Staphylococcus aureus Bacteremia Explained by Immortal Time Bias.

Background: Several studies have suggested that in patients with Staphylococcus aureus bacteremia (SAB) [18F] fluorodeoxyglucose positron emission tomography/computed tomography ([18F]FDG-PET/CT) improves outcome. However, these studies often ignored possible immortal time bias.

Methods: Prospective multicenter cohort study in 2 university and 5 non-university hospitals, including all patients with SAB.

Effect of the introduction of screening for cancer precursor lesions on anal cancer incidence over time in people living with HIV: a nationwide cohort study.

Background: Incidence of anal cancer is high in people living with HIV, particularly in men who have sex with men (MSM). Screening for and treatment of precursor lesions might prevent progression to anal cancer in people living with HIV. We examined trends in incidence of and mortality after anal cancer diagnosis in people living with HIV, including the effect of screening from 2007 onwards, in the Netherlands.

All-Cause and Infection-Related Mortality in Bacteremia, a Multicenter Prospective Cohort Study.

Background: bacteremia (SAB) is a heterogeneous disease with changing epidemiology due to changing demographics and evolving clinical management. SAB is associated with high mortality, but the current fraction of infection-related mortality is less well quantified.

Methods: In a multicenter prospective cohort study of consecutive patients with SAB, we determined clinical features of SAB and determined 90-day mortality and risk factors of all-cause and infection-related mortality.

HIV transmission among acutely infected participants of a Dutch cohort study 2015-2021 is not associated with large, clustered outbreaks.

Objective: Timely identification of acute or early HIV infection (AEHI) is important to help prevent onward transmission, and understanding the number of secondary infections resulting from individuals with AEHI is key to planning HIV prevention services and case finding.

Design: We performed a phylogenetic investigation of a dense sample of individuals with AEHI who took part in the Netherlands Cohort Study on Acute HIV infection (NOVA) in the Netherlands during 2015-2021.

Methods: Transmission clusters were identified using phylogenetic analyses based on HIV pol sequences.

Detecting inappropriate total duration of antimicrobial therapy using semi-automated surveillance.

Objectives: Evaluation of the appropriateness of the duration of antimicrobial treatment is a cornerstone of antibiotic stewardship programs, but it is time-consuming. Furthermore, it is often restricted to antibiotics prescribed during hospital admission. This study aimed to determine whether mandatory prescription-indication registration at the moment of prescribing antibiotics enables reliable automated assessment of the duration of antibiotic therapy, including post-discharge duration, limiting the need for manual chart review to data validation.

The prevalence of persistent bacteraemia in patients with a non-staphylococcal infective endocarditis, a retrospective cohort study.

Background: Current guidelines on the management of infective endocarditis (IE) recommend follow-up blood cultures (FUBCs) to identify persistent bacteraemia, as this has prognostic value and guides treatment decisions. While persistent bacteraemia frequently occurs in Staphylococcus aureus bacteraemia and IE, its prevalence and impact in non-staphylococcal IE is largely unknown. We determined prevalence and prognostic value of persistent bacteraemia in non-staphylococcal IE.