Publications by authors named "Marie-Angélique De Scheerder"

14 Publications

  • Page 1 of 1

Return to sport and work after medial open wedge high tibial osteotomy : a case series.

Acta Orthop Belg 2021 Mar;87(1):117-124

Data on return to work and sport following open wedge high tibial osteotomy (HTO) have been underreported. Furthermore, there is no clear consensus in literature about the postoperative alignment goals following HTO. A retrospective case series was performed to evaluate return to sport and work following open wedge HTO. The University of California, Los Angeles scale, the German classification system according to the Reichsausschuß für Arbeitszeitermittlung, the Tegner score and the Knee injury and Osteoarthritis Outcome Score were used to asses the employment status, sport status and clinical outcome at the time of surgery and at final follow-up, minimum 2 years after surgery. The pre- and postoperative hip knee ankle angle (HKA) were documented. The desired postoperative alignment target was 0°-2° valgus mechanical axis. 30 open wedge HTOs were performed of which 27 patients were retrospectively included in the study. 25 out of 26 patients returned to work and 15 out of 17 patients returned to sport following surgery. Outcome scores were significantly higher after surgery. The mean postoperative HKA was 0,9° of valgus mechanical axis. This study shows excellent outcome in sport and work activity and clinical outcome after open wedge HTO. We furthermore suggest that these outcomes can be obtained with a postoperative alignment of 0°-2° of valgus mechanical axis.
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March 2021

Multiple bone lesions in a patient with fatigue: case report of bone sarcoidosis.

Acta Clin Belg 2021 Mar 28:1-5. Epub 2021 Mar 28.

Department of General Internal Medicine, Ghent University, Ghent University Hospital, Ghent, Belgium.

Bone sarcoidosis is usually considered a rare manifestation of multisystemic sarcoidosis. With the growing use of more sensitive imaging techniques, such as F-FDG PET, the detection rate of bone involvement seems to be increasing. We describe the case of a woman presenting with fatigue and general malaise having multiple bone lesions on F-FDG PET. A broad range of differential diagnoses was considered, including malignancy, infections, metabolic diseases and primary bone tumours, which may have delayed the diagnosis. Diagnostic work-up eventually led to an anatomopathological diagnosis of bone sarcoidosis. Immunosuppressive therapy is often necessary since sarcoid bone lesions - even asymptomatic - generally appear in more extensive forms of the disease with other organ involvement.
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http://dx.doi.org/10.1080/17843286.2021.1903661DOI Listing
March 2021

Motivations, barriers and experiences of participants in an HIV reservoir trial.

J Virus Erad 2021 Mar 23;7(1):100029. Epub 2021 Jan 23.

Department of General Internal Medicine, University Hospital Ghent, Ghent, Belgium.

Objectives: We aimed to investigate the motives, barriers and experiences of HIV-STAR study participants. The HIV-STAR study was an analytical HIV treatment interruption trial (ATI) aiming to evaluate the origin of viral rebound, conducted in Ghent, Belgium.

Methods: A mixed-method study was performed among 11 participants of the HIV-STAR study. Two self-administered questionnaires with 32 and 23 items, respectively, assessed motives, barriers and experiences of the research participants. In-depth interviews were conducted to further explore and understand topics that had emerged from these surveys.

Results: Motives of ATI study participants were primarily related to the improvement of their own health perspectives and to their contribution to find an HIV cure. Barriers for ATI participation mostly related to practical issues, such as difficulty in planning study visits. Ten out of 11 participants reported a very high overall satisfaction and were willing to participate in another ATI. This satisfaction was predominantly linked to clear communication and guidance. Invasive sampling during the ATI was less of a burden than anticipated by participants. However, most participants underestimated the emotional impact of HIV treatment interruption, which was associated with feelings of uncertainty and loss of control. Risk of HIV transmission because of viral rebound was also mentioned as burdensome during this phase.

Conclusions: Involvement in an ATI was positively evaluated by HIV-STAR participants. Contributing to HIV cure research outweighed the burden of study participation for most participants. The latter aspects were attenuated by mutual decision making and the experience of empathy from the research team. Still, issues regarding privacy and the psychosocial impact of treatment interruption, including sexuality and HIV transmissibility, should be addressed in a better way.
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http://dx.doi.org/10.1016/j.jve.2021.100029DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7868726PMC
March 2021

Benefits of antiretroviral therapy initiation during acute HIV infection.

Acta Clin Belg 2020 May 29:1-9. Epub 2020 May 29.

HIV Cure Research Center, Department of Internal Medicine and Pediatrics, Ghent University, Ghent, Belgium.

Objectives: In the last decade, there has been increasing scientific and legislative focus on antiretroviral treatment (ART) for all people living with HIV. Especially early ART initiation, preferably during acute HIV infection, has been named as a promising strategy, both for the individual and for the society. This article will review the benefits and possible future applications of immediate ART initiation during acute HIV infection and explore the remaining hurdles towards this strategy.

Results: On an individual level, initiation of ART during acute HIV infection limits the viral reservoir, preserves immune function, and decreases systemic inflammation. In addition, obtaining viral suppression soon after infection can be beneficial for the society by decreasing the chance of onward HIV transmission. Reducing the transmission will reduce HIV incidence and can curtail HIV-related health expenditure. Furthermore, the favorable immunological and virological profile obtained by treating during acute HIV infection will form an ideal starting point for several HIV cure strategies.

Conclusions: Initiation of ART during acute HIV infection has shown distinct benefits for the individual, for the society, and for future research on HIV cure. In order to implement this strategy, equal focus should be placed on early diagnosis.
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http://dx.doi.org/10.1080/17843286.2020.1770413DOI Listing
May 2020

Rapid viral rebound after analytical treatment interruption in patients with very small HIV reservoir and minimal on-going viral transcription.

J Int AIDS Soc 2020 02;23(2):e25453

Departments of Clinical and Biomedical Sciences, Institute of Tropical Medicine, Antwerp, Belgium.

Introduction: Viral remission after analytical treatment interruption (ATI), termed post-treatment control, has been described in a small proportion of HIV-positive patients. This phenomenon has been separately associated to both low levels of HIV-1 proviral DNA as well as cell-associated RNA. We investigated whether the combination of both parameters could help predict delayed viral rebound after treatment interruption (TI).

Methods: We conducted an open single-arm ATI study in four Belgian HIV reference centres from January 2016 to July 2018. Eligible participants were adults who had fewer than 50 HIV-1 RNA copies/mL for more than two years, more than 500 CD4 cells/µL for more than three months, and were in general good health. Consenting participants who had fewer than 66 copies total HIV-1 DNA (t-DNA) and fewer than 10 copies cell-associated HIV-1 unspliced RNA (US-RNA) per million peripheral blood mononuclear cells (PBMCs), interrupted therapy and were monitored closely. Antiretroviral therapy (ART) was resumed after two consecutive viral loads exceeding 1000 copies or one exceeding 10,000 copies/mL. The primary outcome was the proportion of participants with fewer than 50 HIV-1 RNA copies/mL 48 weeks after TI. Secondary outcomes were time to viral rebound, the frequency of serious adverse events (AEs) and evolution of t-DNA and US-RNA after TI.

Results: All 16 consenting participants who interrupted therapy experienced rapid viral rebound two to eight weeks after TI. No serious AEs were observed. Levels of t-DNA and US-RNA increased after TI but returned to pre-ATI levels after treatment restart. None of the studied demographic, clinical and biological parameters were predictive of time of viral rebound.

Conclusions: The combination of low levels of t-DNA and US-RNA in PBMCs, corresponding respectively to a small and transcriptionally silent viral reservoir, is not predictive of viral remission after TI in patients on ART.
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http://dx.doi.org/10.1002/jia2.25453DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7046528PMC
February 2020

Evaluating predictive markers for viral rebound and safety assessment in blood and lumbar fluid during HIV-1 treatment interruption.

J Antimicrob Chemother 2020 05;75(5):1311-1320

HIV Cure Research Center, Department of Internal Medicine and Paediatrics, Faculty of Medicine and Health Sciences, Ghent University and Ghent University Hospital, Corneel Heymanslaan 10, 9000 Ghent, Belgium.

Background: Validated biomarkers to evaluate HIV-1 cure strategies are currently lacking, therefore requiring analytical treatment interruption (ATI) in study participants. Little is known about the safety of ATI and its long-term impact on patient health.

Objectives: ATI safety was assessed and potential biomarkers predicting viral rebound were evaluated.

Methods: PBMCs, plasma and CSF were collected from 11 HIV-1-positive individuals at four different timepoints during ATI (NCT02641756). Total and integrated HIV-1 DNA, cell-associated (CA) HIV-1 RNA transcripts and restriction factor (RF) expression were measured by PCR-based assays. Markers of neuroinflammation and neuronal injury [neurofilament light chain (NFL) and YKL-40 protein] were measured in CSF. Additionally, neopterin, tryptophan and kynurenine were measured, both in plasma and CSF, as markers of immune activation.

Results: Total HIV-1 DNA, integrated HIV-1 DNA and CA viral RNA transcripts did not differ pre- and post-ATI. Similarly, no significant NFL or YKL-40 increases in CSF were observed between baseline and viral rebound. Furthermore, markers of immune activation did not increase during ATI. Interestingly, the RFs SLFN11 and APOBEC3G increased after ATI before viral rebound. Similarly, Tat-Rev transcripts were increased preceding viral rebound after interruption.

Conclusions: ATI did not increase viral reservoir size and it did not reveal signs of increased neuronal injury or inflammation, suggesting that these well-monitored ATIs are safe. Elevation of Tat-Rev transcription and induced expression of the RFs SLFN11 and APOBEC3G after ATI, prior to viral rebound, indicates that these factors could be used as potential biomarkers predicting viral rebound.
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http://dx.doi.org/10.1093/jac/dkaa003DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7869780PMC
May 2020

Tissue is the issue: when a second biopsy reveals the true diagnosis.

Clin Kidney J 2021 Jan 10;14(1):429-431. Epub 2019 Dec 10.

Department of Internal Medicine, Ghent University Hospital, Ghent, Belgium.

We describe the case of a woman with minimal glomerular changes on initial kidney biopsy. On long-term follow-up, the patient developed nephrotic proteinuria and a second kidney biopsy was performed, which revealed focal segmental glomerulosclerosis (FSGS). Findings from electron microscopy (EM) examination suggested a genetic form of FSGS. Next-generation sequencing showed heterozygosity for a mutation in . Collagen IV nephropathies can be linked to late-onset FSGS. By establishing a genetic cause of FSGS, immunosuppressive treatment can be avoided. This case emphasizes the importance of re-biopsy in cases of a non-explained rise in proteinuria. EM can be helpful in differentiating between primary and secondary FSGS and informing treatment strategies. In cases of adult-onset FSGS that cannot be categorized by clinical-pathological assessment, genetic testing should be considered.
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http://dx.doi.org/10.1093/ckj/sfz165DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7857801PMC
January 2021

HIV Rebound Is Predominantly Fueled by Genetically Identical Viral Expansions from Diverse Reservoirs.

Cell Host Microbe 2019 Sep 27;26(3):347-358.e7. Epub 2019 Aug 27.

HIV Cure Research Center, Department of General Internal Medicine, Ghent University Hospital, Ghent University, Ghent 9000, Belgium. Electronic address:

Viral rebound upon stopping combined antiretroviral therapy poses a major barrier toward an HIV cure. Cellular and anatomical sources responsible for reinitiating viral replication remain a subject of ardent debate, despite extensive research efforts. To unravel the source of rebounding viruses, we conducted a large-scale HIV-STAR (HIV-1 sequencing before analytical treatment interruption to identify the anatomically relevant HIV reservoir) clinical trial. We collected samples from 11 participants and compared the genetic composition of (pro)viruses collected under treatment from different cellular and anatomical compartments with that of plasma viruses sampled during analytical treatment interruption. We found a remarkably heterogeneous source of viral rebound. In addition, irrespective of the compartment or cell subset, genetically identical viral expansions played a significant role in viral rebound. Our study suggests that although there does not seem to be a primary source for rebound HIV, cellular proliferation is an important driver of HIV persistence and should therefore be considered in future curative strategies.
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http://dx.doi.org/10.1016/j.chom.2019.08.003DOI Listing
September 2019

In-depth validation of total HIV-1 DNA assays for quantification of various HIV-1 subtypes.

Sci Rep 2018 11 22;8(1):17274. Epub 2018 Nov 22.

HIV Cure Research Center, Department of Internal Medicine, Ghent University, Ghent, Belgium.

HIV-1 DNA quantification serves as an important reservoir biomarker in HIV cure trials. However, the high genetic diversity of HIV-1 represented by different subtypes may bring inaccuracy in quantifying HIV-1 DNA and a sensitive and validated assay covering diverse HIV-1 subtypes is lacking. Therefore, we cross-validated total HIV-1 DNA assays described in literature using a three-step comparative analysis. First, a bioinformatics tool was developed in-house to perform an in silico evaluation of 67 HIV-1 DNA assays. Secondly, these selected assays were in vitro validated using a panel of different HIV-1 subtypes and, finally, ex vivo assessed on selected patient samples with different HIV-1 subtypes. Our results show that quantification of HIV-1 DNA substantially differs between assays and we advise five best performing HIV-1 DNA assays for ddPCR and qPCR (Schvachsa_2007, Viard_2004, Heeregrave_2009, Van_der_Sluis_2013, Yu_2008 and Yun_2002). This in-depth analysis of published HIV-1 DNA assays indicates that not all assays guarantee an optimal measurement of HIV-1 DNA, especially when looking across subtypes. Using an in-depth cross-validation, we were able to validate HIV-1 DNA assays that are suitable for quantification of HIV-1 DNA in a wide variety of HIV-1 infected patients.
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http://dx.doi.org/10.1038/s41598-018-35403-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6250682PMC
November 2018

Protein expression from unintegrated HIV-1 DNA introduces bias in primary in vitro post-integration latency models.

Sci Rep 2016 12 2;6:38329. Epub 2016 Dec 2.

HIV Cure Research Center, Department of Internal Medicine, Faculty of Medicine and Health Sciences, Ghent University and Ghent University Hospital, Ghent, Belgium.

To understand the persistence of latently HIV-1 infected cells in virally suppressed infected patients, a number of in vitro models of HIV latency have been developed. In an attempt to mimic the in vivo situation as closely as possible, several models use primary cells and replication-competent viruses in combination with antiretroviral compounds to prevent ongoing replication. Latency is subsequently measured by HIV RNA and/or protein production after cellular activation. To discriminate between pre- and post-integration latency, integrase inhibitors are routinely used, preventing novel integrations upon cellular activation. Here, we show that this choice of antiretrovirals may still cause a bias of pre-integration latency in these models, as unintegrated HIV DNA can form and directly contribute to the levels of HIV RNA and protein production. We further show that the addition of reverse transcriptase inhibitors effectively suppresses the levels of episomal HIV DNA (as measured by 2-LTR circles) and decreases the levels of HIV transcription. Consequently, we show that latency levels described in models that only use integrase inhibitors may be overestimated. The inclusion of additional control conditions, such as 2-LTR quantification and the addition of reverse transcriptase inhibitors, is crucial to fully elucidate the actual levels of post-integration latency.
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http://dx.doi.org/10.1038/srep38329DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5133580PMC
December 2016

How far to investigate presumed psychosomatic symptoms: Lessons from a particular case….

Acta Clin Belg 2017 Apr 2;72(2):138-141. Epub 2016 Sep 2.

a Department of General Internal Medicine , University Hospital Ghent , Ghent , Belgium.

We describe a 43-year-old patient with subacute appearance of neurological and atypical complaints of anergia, anorexia and weight loss six months earlier. In spite of several admissions in different hospitals, no underlying somatic cause could be found and he was admitted to a psychiatric hospital with a tentative diagnosis of major depressive disorder. Subsequently, he was referred to the unit of medically unexplained physical symptoms within the department of general internal medicine for assessment by the psychiatrist, involved in this programme. Based on clinical suspicion and red flag symptoms such as involuntary weight loss, a broader internal medicine reassessment, including FDG whole-body PET-CT was requested. Neurological clinical exam showed minor deviations, but neither brain imaging nor a lumbar puncture were contributory. However, FDG PET-CT revealed abnormal moderately to intensely FDG positive lymph nodes in the retroperitoneum. Laparoscopic lymph node biopsy indicated germ cell tumour metastasis. Anti-NMDA antibody positivity allowed a diagnosis of paraneoplastic anti-NMDA encephalitis. Treatment of the underlying disease, a pure seminoma stadium II, consisting of orchidectomy and chemotherapy, resulted in a spectacular regression of 'psychosomatic' symptoms with long-term ability to return to work, and documented disappearance of the anti-NMDA antibody response.
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http://dx.doi.org/10.1080/17843286.2016.1218178DOI Listing
April 2017

Minimal Requirements for Primary HIV Latency Models Based on a Systematic Review.

AIDS Rev 2016 Oct-Dec;18(4):171-183

HIV Translational Research Unit, Department of Internal Medicine, Faculty of Medicine and Health Sciences, Ghent University and Ghent University Hospital, Ghent, Belgium.

Due to the scarcity of HIV-1 latently infected cells in patients, in vitro primary latency models are now commonly used to study the HIV-1 reservoir. To this end, a number of experimental systems have been developed. Most of these models differ based on the nature of the primary CD4+ T-cell type, the used HIV strains, activation methods, and latency assessment strategies. Despite these differences, most models share some common characteristics. Here, we provide a systematic review covering the primary HIV latency models that have been used to date with the aim to compare these models and identify minimal requirements for such experiments. A systematic search on PubMed and Web of Science databases generated a short list of 17 unique publications that propose new in vitro latency models. Based on the described methods, we propose and discuss a generalized workflow, visualizing all the necessary steps to perform such an in vitro study, with the key choices and validation steps that need to be made; from cell type selection until the model readout.
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January 2017

Case report: successful treatment of membranous lupus nephritis with belimumab in an African female immigrant.

Clin Rheumatol 2016 Jun 28;35(6):1649-53. Epub 2015 Dec 28.

Department of Nephrology, AZ Glorieux, Ronse, Belgium.

We describe the case of a 26-year-old African female who was treated successfully with belimumab in a case of severe membranous lupus nephritis and retinal vasculitis, resistant to first line therapy. She presented initially with chronic dacryoadenitis and screening showed nephrotic-range proteinuria. Biopsy of the kidney confirmed the diagnosis of membranous lupus nephritis. Clinical features (joint pain, dacryoadenitis, retinal vasculitis and lupus nephritis) in combination with serology (positive anti-double-stranded DNA (ds-DNA) antibodies, hypocomplementemia) confirmed the diagnosis of systemic lupus erythematosus (SLE). Treatment was immediately initiated with glucocorticosteroids (GCS), mycophenolate mofetil (MMF) and hydroxychloroquine sulphate (Plaquenil®). Tacrolimus was associated but no effect was observed with the proteinuria remaining in the nephrotic range and secondary effects of the glucocorticosteroids becoming a real concern. The patient was started on add-on belimumab with quasi-immediate effect on the proteinuria, making it possible to decrease the dosage of the other immunosuppressants and gradually stop them, even the GCS. The patient is currently in complete remission after 3 years of treatment with belimumab. We were able to stop immunosuppressive treatment but will keep her on antimalarial treatment as the most recent guidelines in treatment of SLE recommend.
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http://dx.doi.org/10.1007/s10067-015-3153-1DOI Listing
June 2016
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