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SLIT2/ROBO signaling in tumor-associated microglia and macrophages drives glioblastoma immunosuppression and vascular dysmorphia KU Leuven

Luiz H Geraldo, Yunling Xu, Laurent Jacob, Laurence Pibouin-Fragner, Rohit Rao, Nawal Maissa, Maite Verreault, Nolwenn Lemaire, Camille Knosp, Corinne Lesaffre, et al.
SLIT2 is a secreted polypeptide that guides migration of cells expressing Roundabout 1 and 2 (ROBO1 and ROBO2) receptors. Herein, we investigated SLIT2/ROBO signaling effects in gliomas. In patients with glioblastoma (GBM), SLIT2 expression increased with malignant progression and correlated with poor survival and immunosuppression. Knockdown of SLIT2 in mouse glioma cells and patient-derived GBM xenografts reduced tumor growth and rendered ...

C-reactive protein as a biomarker for immune-related adverse events in melanoma patients treated with immune checkpoint inhibitors in the adjuvant setting Vrije Universiteit Brussel

Justine Lauwyck, Aline Beckwée, Arno Santens, Julia Katharina Schwarze, Gil Awada, Valerie Vandersleyen, Sandrine Aspeslagh, Bart Neyns

The objective of this study was to evaluate the utility of serum C-reactive protein (CRP) as biomarker for the early diagnosis of immune-related adverse events (irAEs) in melanoma patients treated with immune checkpoint inhibitors (ICIs) in the adjuvant setting, and its potential correlation with relapse-free survival (RFS). Prospectively collected data from 72 melanoma patients treated with adjuvant ICIs were pooled. CRP values at diagnosis ...

Should patients with Phosphomannomutase 2-CDG (PMM2-CDG) be screened for adrenal insufficiency? KU Leuven

Anna Cechova, Tomas Honzik, Andrew C Edmondson, Can Ficicioglu, Mercedes Serrano, Rita Barone, Pascale De Lonlay, Manuel Schiff, Peter Witters, Christina Lam, et al.
PMM2-CDG is the most common congenital disorder of glycosylation (CDG) accounting for almost 65% of known CDG cases affecting N-glycosylation. Abnormalities in N-glycosylation could have a negative impact on many endocrine axes. There is very little known on the effect of impaired N-glycosylation on the hypothalamic-pituitary-adrenal axis function and whether CDG patients are at risk of secondary adrenal insufficiency and decreased adrenal ...

Activity-based cost analysis of laboratory tests in clinical chemistry UZBrussel KU Leuven

Baptist Declerck, Mathijs Swaak, Manuella Jeanne H Martin, Katrien Kesteloot
OBJECTIVES: Since health care budgets are limited and must be allocated efficiently, there is an economic pressure to reduce the costs of health care interventions. This study aims to investigate the cost of testing within a Clinical Chemistry laboratory.

METHODS: This study was conducted in the Clinical Chemistry laboratory of the University Hospital UZ Brussel, Belgium, in which 156 tests were included and an average cost per test ...

Sarcoid-like reaction in a BRAF V600E-mutated metastatic melanoma patient during treatment with BRAF/MEK-targeted therapy Vrije Universiteit Brussel

Jens Tijtgat, Julia Katharina Schwarze, Gil Awada, Bart Neyns, Sandrine Aspeslagh

Treatment with combined BRAF and MEK inhibition is widely accepted as a first-line treatment option for patients with advanced BRAF V600E mutant melanoma. It is generally well-tolerated and has limited side-effects. However, we report a case of a sarcoid-like syndrome induced by treatment with dabrafenib/trametinib (D/T) in a patient with stage IV-M1d melanoma. Sarcoid-like syndrome is a known side-effect of immune checkpoint-inhibition ...

Hypoxia drives murine neutrophil protein scavenging to maintain central carbon metabolism KU Leuven

Emily R Watts, Andrew Jm Howden, Tyler Morrison, Pranvera Sadiku, Jens L Hukelmann, Alex von Kriegsheim, Bart Ghesquière, Fiona Murphy, Ananda S Mirchandani, Duncan C Humphries, et al.
Limiting dysfunctional neutrophilic inflammation while preserving effective immunity requires a better understanding of the processes that dictate neutrophil function in the tissues. Quantitative mass-spectrometry identified how inflammatory murine neutrophils regulated expression of cell surface receptors, signal transduction networks, and metabolic machinery to shape neutrophil phenotypes in response to hypoxia. Through the tracing of labeled ...

Genome wide association study of response to interval and continuous exercise training: the Predict-HIIT study KU Leuven

Camilla J Williams, Zhixiu Li, Nicholas Harvey, Rodney A Lea, Brendon J Gurd, Jacob T Bonafiglia, Ioannis Papadimitriou, Macsue Jacques, Ilaria Croci, Dorthe Stensvold, et al.
BACKGROUND: Low cardiorespiratory fitness (V̇O2peak) is highly associated with chronic disease and mortality from all causes. Whilst exercise training is recommended in health guidelines to improve V̇O2peak, there is considerable inter-individual variability in the V̇O2peak response to the same dose of exercise. Understanding how genetic factors contribute to V̇O2peak training response may improve personalisation of exercise programs. The aim of ...

Chronic Histiocytic Intervillositis With Trophoblast Necrosis Is a Risk Factor Associated With Placental Infection From Coronavirus Disease 2019 (COVID-19) and Intrauterine Maternal-Fetal Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Transm KU Leuven

David A Schwartz, Marcella Baldewijns, Alexandra Benachi, Mattia Bugatti, Rebecca RJ Collins, Danièle De Luca, Fabio Facchetti, Rebecca L Linn, Lukas Marcelis, Denise Morotti, et al.
CONTEXT.—: The number of neonates with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is increasing, and in a few there are reports of intrauterine infection. OBJECTIVE.—: To characterize the placental pathology findings in a preselected cohort of neonates infected by transplacental transmission arising from maternal infection with SARS-CoV-2, and to identify pathology risk factors for placental and fetal infection. ...

How to meet ISO15189:2012 pre-analytical requirements in clinical laboratories? A consensus document by the EFLM WG-PRE KU Leuven

Pieter Vermeersch, Glynis Frans, Alexander von Meyer, Seán Costelloe, Giuseppe Lippi, Ana-Maria Simundic
The International Organization for Standardization (ISO) 15189:2012 standard aims to improve quality in medical laboratories through standardization of all key elements in the total testing process, including the pre-analytical phase. It is hence essential that accreditation bodies, assessing laboratories against ISO15189:2012, pay sufficient attention to auditing pre-analytical activities. However, there are significant differences in how ...

Trehalose as quantitative biomarker for in vivo diagnosis and treatment follow-up in cryptococcomas. KU Leuven

Liesbeth Vanherp, Jennifer Poelmans, Akila Weerasekera, Amy Hillen, Anca R Croitor-Sava, Tania C Sorrell, Katrien Lagrou, Greetje Vande Velde, Uwe Himmelreich
Brain lesions caused by Cryptococcus neoformans or C. gattii (cryptococcomas) are typically difficult to diagnose correctly and treat effectively, but rapid differential diagnosis and treatment initiation are crucial for good outcomes. In previous studies, cultured cryptococcal isolates and ex vivo lesion material contained high concentrations of the virulence factor and fungal metabolite trehalose. Here, we studied the in vivo metabolic profile ...