Diagnostic Value of Microbial Cell-free DNA Sequencing for Suspected Invasive Fungal Infections: A Retrospective Multicenter Cohort Study.

Background: An early diagnosis and treatment of invasive fungal disease (IFD) is associated with improved outcome, but the moderate sensitivity of noninvasive diagnostic tests makes this challenging. Invasive diagnostic procedures such as bronchoalveolar lavage (BAL) have a higher yield but are not without risk. The detection and sequencing of microbial cell-free DNA (mcfDNA) may facilitate a noninvasive diagnosis.

Baseline chest computed tomography for diagnosis of invasive aspergillosis in patients with acute myeloid leukaemia treated with intensive chemotherapy: A retrospective single-centre cohort study.

Background: Invasive pulmonary aspergillosis (IPA) is a relatively common infection in patients with acute myeloid leukaemia (AML), and is associated with high mortality rates. Optimising early detection is key to reduce the burden of IPA in this population. In this retrospective cohort study, we evaluated the added value of baseline chest CT before start of classical induction chemotherapy.

Epidemiological Characteristics and Outcome of Viral Respiratory Tract Infections in the First Year After Allogeneic Hematopoietic Cell Transplantation.

Adverse outcomes of viral respiratory tract infections (RTIs) have been reported in recipients of allogeneic hematopoietic cell transplantation. Using a laboratory-developed multiparameter polymerase chain reaction in a consecutive series of 242 patients, we found the highest incidence of viral RTI in the preengraftment phase. The occurrence of multiple episodes of viral RTI or viral pneumonia was significantly associated with a higher hazard of nonrelapse mortality in the first year after transplantation.

Retrospective Multicenter Evaluation of the VirClia Galactomannan Antigen Assay for the Diagnosis of Pulmonary Aspergillosis with Bronchoalveolar Lavage Fluid Samples from Patients with Hematological Disease.

Galactomannan (GM) testing of bronchoalveolar lavage (BAL) fluid samples has become an essential tool to diagnose invasive pulmonary aspergillosis (IPA) and is part of diagnostic guidelines. Enzyme-linked immunosorbent assays (ELISAs) (enzyme immunoassays [EIAs]) are commonly used, but they have a long turnaround time. In this study, we evaluated the performance of an automated chemiluminescence immunoassay (CLIA) with BAL fluid samples.

Immunologic Monitoring after Allogeneic Stem Cell Transplantation: T-SPOT.CMV and QuantiFERON-CMV, Are They the Same?

Despite prophylactic and preemptive strategies, cytomegalovirus (CMV) reactivation and disease remains major concerns after allogeneic hematopoietic stem cell transplantation (allo-HSCT). In recent years, immunologic monitoring using CMV commercially available IFN-γ release assays (IGRAs) has gained interest to better risk-stratify immunocompromised patients or to guide prophylactic therapy. CMV-IGRA can quantify CMV cell-mediated immunity by measuring the IFN-γ that is released by CD4 and CD8 T lymphocytes in the presence of CMV antigens.

Clinical Impact of Polymerase Chain Reaction-Based Aspergillus and Azole Resistance Detection in Invasive Aspergillosis: A Prospective Multicenter Study.

Background: Invasive aspergillosis (IA) by a triazole-resistant Aspergillus fumigatus is associated with high mortality. Real-time resistance detection will result in earlier initiation of appropriate therapy.

Methods: In a prospective study, we evaluated the clinical value of the AsperGenius polymerase chain reaction (PCR) assay in hematology patients from 12 centers.

Case report: Hemorrhagic fever with renal syndrome presenting as hemophagocytic lymphohistiocytosis.

Hemophagocytic lymphohistiocytosis may occur in patients with genetic predisposition and in sporadic cases due to malignancy or infection. We describe a 49-year old man with hemorrhagic fever, type 1 respiratory insufficiency and acute kidney injury. Diagnostic work up showed a hyperinflammatory syndrome, hypertriglyceridemia, hemophagocytosis, very high ferritin and significantly elevated sCD25.

Blood Mucorales PCR to track down and Mucorales co-infections in at-risk hematology patients: A case-control study.

Introduction: Serum Mucorales PCR can precede the final diagnosis of invasive mucormycosis by several days or weeks and could therefore be useful as a non-invasive screening tool.

Methods: We assessed the performance of a commercial Mucorales PCR assay (MucorGenius®, PathoNostics, Maastricht, The Netherlands) on prospectively collected banked sera from hematology patients at risk for invasive mould infections. We evaluated if there is an underestimated incidence of missed Mucorales co-infections in patients with invasive aspergillosis (IA).

Infectious diarrhea after allogeneic hematopoietic cell transplantation assessed by a multiplex polymerase chain reaction assay.

Objectives: To determine the incidence of infectious diarrhea after allogeneic hematopoietic cell transplantation (HCT) using a multiplex polymerase chain reaction assay and assess risk factors for developing infectious diarrhea.

Methods: This was a single-center retrospective study of 140 consecutive allogeneic HCT recipients. Infectious diarrhea was assessed using a laboratory-developed multiplex polymerase chain reaction the first year after transplantation.

Performance of the JF5-Based Galactomannoprotein EIA Compared to the Lateral Flow Device and the Galactomannan EIA in Serum and Bronchoalveolar Lavage Fluid.

Early diagnosis of invasive aspergillosis is an important factor to improve survival but remains challenging. The detection of Aspergillus antigens is included in the consensus case definitions of the European Organization for Research and Treatment of Cancer and the National Institute of Allergy and Infectious Diseases Mycoses Study Group as a criterion of "probable" invasive aspergillosis. JF5, a mouse IgG3 monoclonal antibody detecting an Aspergillus mannoprotein, has already been implemented as a lateral flow device (LFD).

A unique phenotype of longitudinal extensive transverse myelitis in autoimmune lymphoproliferative syndrome.

A 49-year-old patient with a history of lymphoproliferation and autoimmune cytopenias presented with unexplained longitudinal extensive transverse myelitis. Flow cytometry on peripheral blood showed an elevated level of double negative T lymphocytes, a finding typical for autoimmune lymphoproliferative syndrome (ALPS). Inborn error of immunity (IEI) gene panel demonstrated a heterozygous variant in the FAS gene (c.

Early high antibody titre convalescent plasma for hospitalised COVID-19 patients: DAWn-plasma.

Background: Several randomised clinical trials have studied convalescent plasma for coronavirus disease 2019 (COVID-19) using different protocols, with different severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) neutralising antibody titres, at different time-points and severities of illness.

Methods: In the prospective multicentre DAWn-plasma trial, adult patients hospitalised with COVID-19 were randomised to 4 units of open-label convalescent plasma combined with standard of care (intervention group) or standard of care alone (control group). Plasma from donors with neutralising antibody titres (50% neutralisation titre (NT)) ≥1/320 was the product of choice for the study.

A Large Retrospective Assessment of Voriconazole Exposure in Patients Treated with Extracorporeal Membrane Oxygenation.

Background: Voriconazole is one of the first-line therapies for invasive pulmonary aspergillosis. Drug concentrations might be significantly influenced by the use of extracorporeal membrane oxygenation (ECMO). We aimed to assess the effect of ECMO on voriconazole exposure in a large patient population.

Point of care aspergillus testing in intensive care patients.

Background: Invasive pulmonary aspergillosis (IPA) is an increasingly recognized complication in intensive care unit (ICU) patients, especially those with influenza, cirrhosis, chronic obstructive pulmonary disease, and other diseases. The diagnosis can be challenging, especially in the ICU, where clinical symptoms as well as imaging are mostly nonspecific. Recently, Aspergillus lateral flow tests were developed to decrease the time to diagnosis of IPA.

Outpatient parenteral antifungal therapy (OPAT) for invasive fungal infections with intermittent dosing of liposomal amphotericin B.

Triazole resistant A. fumigatus has been documented in many parts of the world. In the Netherlands, incidence is now above 10% and results in the need for long-term parenteral therapy with liposomal amphotericin B (LAmB).

High-dose posaconazole for azole-resistant aspergillosis and other difficult-to-treat mould infections.

Background: Oral follow-up therapy is problematic in moulds with reduced azole-susceptibility, such as azole-resistant Aspergillus fumigatus infection. Currently, only intravenous liposomal amphotericin B (L-AmB) is advocated by guidelines for the treatment of azole-resistant aspergillosis infections. Preclinical research indicates that high-dose posaconazole (HD-POS) might be a feasible option provided that high drug exposure (ie POS serum through levels >3 mg/L) can be achieved and is safe.

Lateral flow assays for diagnosing invasive pulmonary aspergillosis in adult hematology patients: A comparative multicenter study.

Fast diagnosis of invasive pulmonary aspergillosis (IPA) is essential as early adequate therapy improves survival. However, current microbiological methods suffer from a low sensitivity or a long turnaround time, often as a result of batching. Recently, two lateral flow assays for diagnosing IPA have been CE (Conformité Européenne)-marked and commercialized.