Lars Heggelund

Vestre Viken Hospital Trust · Department of Internal Medicine

Lack of rapid and comprehensive microbiological diagnosis in patients with community acquired pneumonia (CAP) hampers appropriate antimicrobial therapy. This study evaluates the real-world performance of the BioFire FilmArray Pneumonia panel plus (FAP plus ) and explores the feasibility of evaluation in a randomised controlled trial. Patients prese...

Purpose Studies on aetiology of community-acquired pneumonia (CAP) vary in terms of microbial sampling methods, anatomical locations, and laboratory analyses, since no gold standard exists. In this large, multicentre, retrospective, regional study from Norway, our primary objective was to report the results of a strategic diagnostic stewardship int...

Background: Virtually all living organisms, including microbes and humans, depend on iron to survive and grow. During an infection, the plasma level of iron and several iron-related proteins change substantially. We hypothesized that iron and iron-related proteins could predict short- and long-term outcomes in community-acquired pneumonia. Method...

The association between pulmonary sequelae and markers of disease severity, as well as pro-fibrotic mediators, were studied in 108 patients 3 months after hospital admission for COVID-19. The COPD assessment test (CAT-score), spirometry, diffusion capacity of the lungs (DL CO ), and chest-CT were performed at 23 Norwegian hospitals included in the...

PurposeStudies on aetiology of community-acquired pneumonia (CAP) vary in terms of microbial sampling methods, anatomical locations, and laboratory analyses, since no gold standard exists. In this large, multicentre, retrospective, regional study from Norway, our primary objective was to report the results of a strategic diagnostic stewardship inte...

Objective To test the hypotheses that blood biomarkers for nervous system injury, serum concentrations of neurofilament light chain protein (NfL) and glial fibrillary acidic protein (GFAp) can serve as biomarkers for disease severity in COVID-19 patients. Methods Forty-seven inpatients with confirmed COVID-19 had blood samples drawn on admission f...

Background The ISARIC prospective multinational observational study is the largest cohort of hospitalized patients with COVID-19. We present relationships of age, sex, and nationality to presenting symptoms. Methods International, prospective observational study of 60 109 hospitalized symptomatic patients with laboratory-confirmed COVID-19 recruit...

BacgroundSuper-infections in COVID-19 patients with acute respiratory distress syndrome (ARDS) on mechanical ventilation were initially reported to be rare. Little is known of their incidence after dexamethasone was introduced as standard care. We aimed to determine the incidence and characteristics of superinfections in mechanically ventilated COV...

No abstract available for this article.

Due to the highly variable clinical phenotype of Coronavirus disease 2019 (COVID-19), deepening the host genetic contribution to severe COVID-19 may further improve our understanding about underlying disease mechanisms. Here, we describe an extended GWAS meta-analysis of 3,260 COVID-19 patients with respiratory failure and 12,483 population control...

Background: New treatment modalities are urgently needed for patients with COVID-19. The World Health Organization (WHO) Solidarity trial showed no effect of remdesivir or hydroxychloroquine (HCQ) on mortality, but the antiviral effects of these drugs are not known. Objective: To evaluate the effects of remdesivir and HCQ on all-cause, in-hospit...

Background Iron is crucial for survival and growth of microbes. Consequently, limiting iron availability is a human antimicrobial defense mechanism. We explored iron and iron-related proteins as potential biomarkers in community-acquired pneumonia and hypothesized that infection-induced changes in these potential biomarkers differ between groups of...

https://papers.ssrn.com/sol3/papers.cfm?abstract_id=3774182

In SARS-CoV-2 infection there is an urgent need to identify patients that will progress to severe COVID-19 and may benefit from targeted treatment. In this study we analyzed plasma cytokines in COVID-19 patients and investigated their association with respiratory failure (RF) and treatment in Intensive Care Unit (ICU). Hospitalized patients (n = 34...

Background: A high proportion of COVID-19 patients have cardiac involvement, even those without known cardiac disease. Downregulation of angiotensin converting enzyme 2 (ACE2), a receptor for SARS-CoV-2 and the renin-angiotensin system, as well as inflammatory mechanisms have been suggested to play a role. ACE2 is abundant in the gut and associate...

Background: The pathogenesis of COVID-19 is still incompletely understood, but seems to involve immune activation and immune dysregulation. Objective: We examined parameters of activation of different leukocyte subsets in COVID-19 infected patients in relation to disease severity. Methods: We analyzed plasma levels of myeloperoxidase (MPO, neu...

Respiratory failure in the acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic is hypothesized to be driven by an overreacting innate immune response, where the complement system is a key player. In this prospective cohort study of 39 hospitalized coronavirus disease COVID-19 patients, we describe systemic complement activation and its a...

Objective To test the hypotheses that serum concentrations of neurofilament light chain protein (NfL) and glial fibrillary acidic protein (GFAp) can serve as biomarkers for disease severity in COVID-19 patients. Methods Forty-seven inpatients with confirmed COVID-19 had blood samples drawn on admission for assessing serum biomarkers of CNS injury b...

Background: In SARS-CoV-2 infection there is an urgent need to identify patients that will progress to severe COVID-19 and may benefit from targeted treatment. Objectives: Analyze plasma cytokines in COVID-19 patients and investigate their association with respiratory failure (RF) and treatment in Intensive Care Unit (ICU). Method: Hospitalized pa...

Background: Biomarkers may facilitate clinical decisions in order to guide antimicrobial treatment and prediction of prognosis in community-acquired pneumonia (CAP). We measured serum C-reactive protein, procalcitonin (PCT) and calprotectin levels, and plasma pentraxin 3 (PTX3) and presepsin levels, along with whole-blood white cell counts, at thre...

Background Disease severity and outcome in community-acquired pneumonia (CAP) depend on the host and on the challenge of the causal microorganism(s). We measured levels of immunoglobulins (Igs) and complement in 257 hospitalized adults with CAP and examined the association of low levels of Igs or complement to microbial etiology, disease severity a...

Background: The inflammatory response in community-acquired pneumonia (CAP) is orchestrated through activation of cytokine networks and the complement system. We examined the association of multiple cytokines and the terminal complement complex (TCC) with microbial etiology, disease severity and short-term outcome. Materials and methods: Plasma...

Background and aims Chronic hepatitis C virus (HCV) genotype 3 infection with advanced liver disease has emerged as the most challenging to treat. We retrospectively assessed the treatment outcome of sofosbuvir (SOF) based regimes for treatment of HCV genotype 3 infections in a real life setting in Scandinavia. Methods Consecutive patients with ch...

Background Low vitamin D status has been associated with short-term (30-day) mortality in hospitalized adults with community-acquired pneumonia (CAP). Data on its prevalence in these patients are scarce, and impact on long-term prognosis is unknown. We examined the prevalence of vitamin D deficiency and inadequacy and their effect on long-term mort...

Minimal data set underlying the findings in the study. Variable instructions are in sheet 2. (XLSX)

Identification of confounders in the association between vitamin D status (25-hydroxyvitamin D 30–49 nmol/L or <30 nmol/L versus ≥50 nmol/L [reference category]) and long-term all-cause mortality after hospitalization for CAP. (DOCX)

Identification of potential confounders: Univariable associations between long-term all-cause mortality after hospitalization for CAP and factors found to have a significant association with vitamin D status. (DOCX)

Causes of death and vitamin D status measured at admission in 72 patients who died during long-term follow-up after hospitalization for CAP. (DOCX)

The inclusion process for the study population. (DOCX)

Summary of microbiological specimen collection and methods. (DOCX)

Background: Contributors to long-term mortality in patients with community-acquired pneumonia (CAP) remain unclear, with little attention paid to pneumonia etiology. We examined long-term survival, causes of death, and risk factors for long-term mortality in adult patients who had been hospitalized for CAP, with emphasis on demographic, clinical,...

The inclusion process for the study population. (DOCX)

Minimal data set underlying the findings in the study. Variable instructions are in sheet 2. (XLSX)

Plot of the Cox-Snell residuals from the model. The curve is very close to the diagonal indicating a good model fit. (EPS)

Microbial findings in 162 hospital survivors with an etiologically established diagnosis of community-acquired pneumonia. (DOCX)

Background and aims: On-going risk behaviour can lead to hepatitis C virus (HCV) reinfection following successful treatment. We aimed to assess the incidence of persistent HCV reinfection in a population of people who inject drugs (PWID) who had achieved sustained virological response (SVR) seven years earlier. Methods: In 2004-2006 we conducted...

Despite recent advances in microbiological techniques, the etiology of community-acquired pneumonia (CAP) is still not well described. We applied polymerase chain reaction (PCR) and conventional methods to describe etiology of CAP in hospitalized adults and evaluated their respective diagnostic yields. 267 CAP patients were enrolled consecutively o...

We present a case of Corynebacterium pseudotuberculosis pneumonia in a veterinary student, with molecular genetic evidence of acquisition during laboratory work, an observation relevant for laboratory personnel working with C pseudotuberculosis isolates. The patient was clinically cured with 14 months trimethoprim/sulfamethoxazole and rifampicin co...

To determine the prevalence and predictors of positive interferon-gamma release assays (IGRAs) and tuberculin skin tests (TSTs) in human immunodeficiency virus (HIV) infected patients in Norway, a low tuberculosis (TB) endemic country. Multicentre cross-sectional study of 298 HIV patients tested with QuantiFERON®-TB Gold In-Tube (QFT-GIT), T-SPOT®....

CCL19 and CCL21 and their receptor CCR7 are expressed constitutively within lymphoid organs, regulating lymphocyte homing. Recent studies suggest that these chemokines may have inflammatory properties. We hypothesized a role of CCL19/CCL21 in human immunodeficiency virus (HIV) infection by promoting inflammation. We examined the expression of CCL19...

While some chemokines are thought to be protective in HIV-infected individuals by their ability to block HIV entry into T cells and macrophages, chemokines could also have harmful effects in HIV infection through their ability to promote inflammation. Here, we examined the regulation and the effects of CXCL16, a newly discovered chemokine of the CX...

The CCR7 ligands, CCL19 and CCL21, coordinate lymph node homing of naive and central memory T cells. In untreated HIV-infected patients, serum levels of CCL19 and CCL21 showed a biphasic pattern during progression; a marked increase was followed by a decline in patients with advanced immunodeficiency. During highly active antiretroviral therapy, a...

Background: CCL19 and CCL21 not only orchestrate lymphocyte and dendritic cell migration, but seem also to regulate their immunogenic potential. HIV infection is characterized by a persistent and inappropriate immune activation. Based on the inflammatory properties of CCL19 and CCL21, we hypothesized a pathogenic role of these chemokines in HIV inf...

Although neutrophil gelatinase-associated lipocalin (NGAL) may play a pivotal role in the innate immune response, there are currently no data on NGAL levels in human immunodeficiency virus (HIV)-infected patients. In this study we aimed to examine the regulation of NGAL in HIV infection. The regulation of NGAL in HIV infection was examined by diffe...

Staphylococcus aureus, including methicillin-resistant strains (MRSA), may cause a wide range of infections involving skin and soft tissue, as well as bone, airways, and endovascular grafts.

Increasing data support the involvement of chemokines in atherogenesis. However, although several studies have shown increased chemokine levels in adult patients, the literature is virtually devoid of data on chemokines in children with hypercholesterolemia. We examined the gene expression of chemokines in peripheral blood mononuclear cells (PBMCs)...

Mannose-binding lectin (MBL) is a soluble receptor of the innate immune system, probably contributing to antimicrobial defence. The possible role of MBL in HIV infection is unclear. Peripheral blood mononuclear cells (PBMCs) from 28 HIV-infected patients and 13 healthy controls were stimulated with MBL and costimulated with HIV-1 gp120 or mannan fr...

The importance of the innate immune system, including mannose-binding lectin and the complement system, in common variable immunodeficiency is unclear. The objective of this study was to evaluate mannose-binding lectin and the complement system in relation to clinical and immunological parameters in patients with common variable immunodeficiency. C...

Transplant-associated coronary artery disease (TxCAD) is a major cause of post-transplant graft failure. The aim of this study was to investigate a possible role of mannose-binding lectin (MBL) deficiency and complement activation in TxCAD. In a prospective study of heart transplant recipients (n=38) with a follow-up of 5.3+/-1.3 years (range: 0.9-...

We report that patients with AIDS have lower serum levels of soluble toll-like receptor 2 (sTLR2) compared with healthy controls and patients with less advanced HIV infection. sTLR2 levels are relatively stable during longitudinal testing, with lower levels in progressors than non-progressors. No correlations between sTLR levels and CD4/CD8 T-cell...