Publications by authors named "Kullberg B"

Background: Rezafungin is an echinocandin approved in the US and EU to treat candidaemia and/or invasive candidiasis. This post-hoc, pooled analysis of the Phase 2 STRIVE and Phase 3 ReSTORE trials assessed rezafungin versus caspofungin in patients with candidaemia and/or invasive candidiasis (IC) in the intensive care unit (ICU) at randomisation.

Methods: STRIVE and ReSTORE were randomised double-blind trials in adults with systemic signs and mycological confirmation of candidaemia and/or IC in blood or a normally sterile site ≤ 96 h before randomisation.

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  • Rezafungin, a new once-weekly echinocandin, showed similar effectiveness to caspofungin in treating candidemia and invasive candidiasis in the ReSTORE trial, particularly in terms of day 30 all-cause mortality and day 14 global cure rates.
  • The study involved patients aged 18 and older, comparing the outcomes of those receiving rezafungin to those on caspofungin, with specific focus on patients who had a positive culture close to the time of treatment randomization.
  • Results indicated comparable safety and efficacy between the two treatments, with rezafungin showing potential advantages in early mycological response, suggesting it could be an effective option for treatment.
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  • * Researchers analyzed cytokine production before and after antibiotic treatment in over 1,000 patients, discovering a negative relationship between antibody production and IL-10 levels, as well as increased IL-1Ra in those with advanced disease.
  • * Genome-wide mapping identified 34 cytokine quantitative trait loci (cQTLs), including 31 new ones, linking immune responses to Lyme borreliosis susceptibility and offering insights relevant to other immune-related diseases.
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  • Genetic variation affects how individuals respond to infections, influencing both susceptibility and symptoms of diseases like Lyme borreliosis (LB).
  • The study involved genome-wide association studies of 1,138 LB patients and healthy controls, evaluating genetic variants, cytokine responses, and antibody production related to the disease.
  • A newly identified genetic variant, rs1061632, was linked to increased susceptibility to LB and associated with immune response alterations, highlighting the genetic factors influencing LB susceptibility and bacterial clearance.
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  • The document outlines the goal of creating standardized research definitions for invasive fungal diseases (IFD) in adult ICU patients without typical risk factors for these infections.
  • A panel of experts assessed existing definitions and lab tests for IFD, using the RAND/UCLA method to reach a consensus on new definitions.
  • Key standardized definitions were made for conditions like invasive candidiasis and aspergillosis, but more data is needed for other IFDs, with the intent to enhance future research studies.
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Objectives: To describe the course of symptoms reported by patients with symptoms attributed to Lyme borreliosis (LB) without being subsequently diagnosed with LB.

Methods: We performed a prospective cohort study with patients presenting at the outpatient clinic of two clinical LB centres. The primary outcome was the prevalence of persistent symptoms, which were defined as clinically relevant fatigue (CIS, subscale fatigue), pain (SF-36, subscale bodily pain), and cognitive impairment (CFQ) for ≥ 6 months and onset < 6 months over the first year of follow-up.

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Background: Patients treated for Lyme borreliosis (LB) frequently report persistent symptoms. Little is known about risk factors and etiology.

Methods: In a prospective observational cohort study with a follow-up of one year, we assessed a range of microbiological, immunological, genetic, clinical, functional, epidemiological, psychosocial and cognitive-behavioral variables as determinants of persistent symptoms after treatment for LB.

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  • Rezafungin is a newly approved drug for treating candidaemia and invasive candidiasis, showing effectiveness and safety comparable to caspofungin in clinical trials.
  • The analysis combined data from two trials (STRIVE and ReSTORE) involving 294 patients worldwide, where both drugs were evaluated for their efficacy and safety profiles.
  • Results indicated similar 30-day mortality rates for both treatments (around 19%), and a higher rate of mycological response by day 5 in the rezafungin group, with both medications exhibiting comparable safety.
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Objective: The diagnosis of Lyme borreliosis is based on two-tier testing using an ELISA and Western blot. About 5-10% of patients report persistent symptoms of unknown etiology after treatment, resulting in substantial difficulties in further diagnostic workup. This paper presents a study aimed at determining whether serology can differentiate between patients with persistent symptoms attributed to Lyme and other patients with Lyme borreliosis.

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Background: Rezafungin is a next-generation, once-a-week echinocandin in development for the treatment of candidaemia and invasive candidiasis and for the prevention of invasive fungal disease caused by Candida, Aspergillus, and Pneumocystis spp after blood and marrow transplantation. We aimed to compare the efficacy and safety of intravenous rezafungin versus intravenous caspofungin in patients with candidaemia and invasive candidiasis.

Methods: ReSTORE was a multicentre, double-blind, double-dummy, randomised phase 3 trial done at 66 tertiary care centres in 15 countries.

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Independence is crucial for the quality and credibility of scientific recommendations and guidelines. The composition of advisory committees requires a full understanding of the relationships and interests of prospective committee members. In addition to financial relationships, intellectual interests, professional interests, and reputation may also play a role.

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  • Monocytes can be 'trained' or 'tolerized' by specific stimuli, leading to altered immune responses, and changes in glucose metabolism are key to this process.
  • Exposure to Borrelia burgdorferi reduces cytokine production in monocytes and lowers glycolysis levels, indicating long-term immune response changes.
  • A gene called MFAP3L was identified as influencing lactate production post-B. burgdorferi exposure, with validation showing its role in cytokine production and the involvement of platelets and certain platelet-derived factors in this process.
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  • Researchers evaluated the effectiveness of three cellular tests for detecting Lyme borreliosis in comparison to standard serological testing, aiming to improve diagnosis, especially in early infection stages.
  • The study involved a nationwide analysis in the Netherlands, including 271 patients with Lyme and 269 controls, to determine how well the cellular tests performed in terms of sensitivity (ability to correctly identify infected individuals) and specificity (ability to correctly identify non-infected individuals).
  • Findings revealed that the standard serological test had higher specificity than the cellular tests, but the cellular tests varied significantly in sensitivity, indicating mixed results for their reliability in diagnosing Lyme borreliosis.
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Biologics that block the T helper (Th) 17 pathway are very effective in the treatment of psoriasis and other inflammatory diseases. However, IL-17 is also crucial for antifungal host defense, and clinical trial data suggest an increase in the incidence of Candida infections during IL-17 inhibitor (IL-17i) therapy. We investigated the innate and adaptive immune responses of patients with psoriasis with a history of skin and/or mucosal candidiasis during IL-17i or IL-12/23 inhibitor therapy, comparing those responses with those of healthy controls.

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Introduction: Intra-abdominal infections represent the second most frequently acquired infection in the intensive care unit (ICU), with mortality rates ranging from 20% to 50%. Candida spp. may be responsible for up to 10-30% of cases.

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Laboratory diagnosis of Lyme borreliosis (LB) is mainly based on serology, which has limitations, particularly in the early stages of the disease. In recent years there have been conflicting reports concerning a new diagnostic tool using the cytokine interferon-gamma (IFN-γ). Previous studies have generally found low concentrations of IFN-γ in early LB infection.

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Genetic defects in interleukin-12/23/17 immunity are associated with an increased risk of Staphylococcus aureus and herpesvirus skin infections. This study analysed spontaneous safety reports from the WHO Pharmacovigilance Center of bacterial skin or herpesvirus infections associated with secukinumab, ustekinumab and tumour necrosis factor-α inhibitors. Associations found in disproportionality analyses were expressed as reporting odds ratios (ROR).

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Background: Biologics directed against the T-helper (Th)-17 pathway have been approved for several inflammatory diseases. Interleukin (IL)-17 is involved in anti- host defense, and clinical trials suggested increased candidiasis incidence during IL-17 inhibitor therapy. We describe the worldwide epidemiology of candidiasis during Th17 inhibitor therapy, and immunological mechanisms involved in candidiasis susceptibility.

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  • A large prospective study investigated long-lasting symptoms in adults treated for Lyme borreliosis (LB), comparing these patients to general population and tick-bite controls.
  • The study found that 27.2% of LB patients experienced persistent symptoms, notably higher than the 21.2% and 23.3% found in the general population and tick-bite groups, respectively.
  • These persistent symptoms included more severe fatigue, cognitive impairment, and pain among erythema migrans patients compared to those without LB, suggesting an association between LB and lingering health issues in some patients.
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Introduction/objective: Expectancies about symptom improvement or deterioration are reliable predictors of symptom progression and treatment outcomes (symptom resolution or symptomatic improvement) in many (non-)pharmacological studies and treatments. This study examined predictors of symptom improvement after antimicrobial therapy for persistent symptoms attributed to Lyme disease, hypothesizing particularly pre-treatment expectancies regarding symptom improvement to be predictive.

Methods: A predictive study was performed on pre-treatment and post-treatment individual characteristics, including expectancies, and physical and mental health-related quality of life (HRQoL) from the PLEASE-trial comparing randomized 12-weeks of doxycycline, clarithromycin-hydroxychloroquine, or placebo following 2 weeks of intravenous ceftriaxone.

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The EORTC/MSGERC recently revised and updated the consensus definitions of invasive fungal disease (IFD). These definitions primarily focus on patients with cancer and stem cell or solid-organ transplant patients. They may therefore not be suitable for intensive care unit (ICU) patients.

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Invasive fungal diseases (IFDs) often represent complicated infections in complex patient populations. The Center of Expertise in Mycology Radboudumc/CWZ (EMRC) organizes a biweekly multidisciplinary mycology meeting to discuss patients with severe fungal infections and to provide comprehensive advice regarding diagnosis and treatment. Here, we describe the patient population discussed at these meetings during a one-year period with regards to their past medical history, diagnosis, microbiological and other diagnostic test results and antifungal therapy.

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